BIORESORBABLE, IMPLANTABLE DEVICE HAVING CONTROLLED DRUG DELIVERY

A bioresorbable, implantable device having controlled drug delivery is disclosed herein. The bioresorbable, implantable device is configured as a film, a roll, a tube, and a stent. The bioresorbable, implantable device is configured to release an active ingredient (the “drug”) from the bioresorbable, implantable device when the bioresorbable, implantable device is implanted within a body. The bioresorbable, implantable device is configured to control the onset of the release of the drug, the sequence of drug delivery, and the duration of drug delivery by embedding the drug within at least one therapeutic layer positioned within bioresorbable, implantable device.

FIELD OF INVENTION

The present invention relates to drug-eluting medical devices.

BACKGROUND OF INVENTION

When we talk to medical doctors, we find that there is a need for a medical device that provides mechanical support and local drug delivery. Many surgical procedures include the treatment of an injury that requires mechanical support to temporarily stabilize the treated area during healing and drug delivery to control scar tissue formation. Our bioresorbable film, roll, tube, and stent can satisfy this unmet need.

One example of the need to provide mechanical support and drug delivery is found in the treatment of atherosclerosis. Atherosclerosis is presently treated with an angioplasty procedure that comprises the steps of inserting an uninflated balloon catheter into a constricted segment of an artery, expanding the balloon in a way that compresses the plaque buildup against the artery so that the artery's passageway is opened to restore blood flow, deflating the balloon catheter, and then withdrawing the balloon catheter from the treated segment (the “treatment site”). The angioplasty procedure imparts an injury on the artery that can form scar tissue (aka neointimal hyperplasia) that can reclose the artery as it heals from the injury. A stent is delivered to the newly opened artery segment in a reduced diameter and expanded in diameter to provide radial support to the artery until it heals. The stent can also deliver a drug that inhibits scar tissue formation (neointimal growth). Historically, stents are made of metal alloys. The problem with a metal stent is that patients that suffer from atherosclerosis generally do not change their lifestyle choices and many patients will require a future re-vascularization procedure. The permanent metal implant can interfere with the re-vascularization procedure. In contrast, a bioresorbable stent provides temporarily radial support and drug delivery until the artery is healed and then the bioresorbable stent dissolves and is eliminated from the treated artery segment.

The industry's first generation bioresorbable stents had thick struts that protruded too far into the passageway of the artery and therefore sometimes created a thrombotic condition. Additionally, the first generation bioresorbable stents were made of low molecular weight bioresorbable polymers that were brittle and could fracture when over-expanded by the balloon catheter during deployment within the treatment site. The low molecular weight bioresorbable polymer also had a problem of fast dismantling, which resulted in early strut discontinuities that reduces the stent's radial strength. Additionally, the industry's first generation bioresorbable stents were radiolucent except for small radiopaque markers located on the proximal and distal ends of the stent, which made it difficult for clinicians to determine if the bioresorbable stent was in apposition with the artery.

The prior art bioresorbable stents have a thin drug-polymer matrix coating adhered to the outer surface of the stent. The thin surface applied coating typically released the drug during the first 90 days post implantation. The rapidly released drug has little time to diffuse into the adjacent tissue because liquid body fluids wash at least one part of the released drug away from the treatment site. To compensate for drug losses into the bloodstream the prior stents had high drug dosages that have been shown to inhibit healing of the injury imparted on opened segment of the artery. Our innovative bioresorbable stent is superior because the drug is positioned in strategically located layers that can be located on the outside surface(s) and/or inside of the thickness of the bioresorbable stent. These drug layers control the drug delivery onset time and release rate of the drug so that the drug can more effectively diffuse into the local tissue without side effects. For example, in vascular applications the released drug can prevent scar tissue development without interfering endothelial cells covering the struts.

SUMMARY

The present invention is a bioresorbable, implantable medical device. The bioresorbable, implantable medical device comprises the configuration of a film, a roll, a tube and/or a stent (aka a “Scaffold”). The bioresorbable, implantable device provides a therapeutic treatment. For example, the bioresorbable, implantable device provides mechanical support and/or drug delivery. The bioresorbable, implantable device comprises a material that undergoes a resorption process, wherein the term “resorption” refers to the material losing its mass after the bioresorbable, implantable device is implanted in the body. In layman's terms the bioresorbable material can be thought of as a material that dissolves and disappears from the implantation site over time while the therapy is performed and/or after the therapy is completed.

A bioresorbable stent, which is sometimes referred to as a scaffold, is fundamentally bioresorbable material configured into a series of sinusoidal or zigzag shaped linear ring struts that are held together with connecting link struts (collectively hereinafter referred to as the “struts”). Although at first glance the external appearance of all stents may look similar, there are significant differences within the struts' wall thicknesses. The present invention is different because the stent struts comprise layers.

The present invention is a bioresorbable stent comprising at least one raw material comprising ultra-high weight average molecular weight (Mw) bioresorbable polymer(s). Including at least one ultra-high weight average molecular weight (Mw) bioresorbable polymer raw material within the stent is beneficial because it produces a stronger stent. Additionally, the ultra-high weight average molecular weight (Mw) bioresorbable polymer provides greater ductility than a lower weight average molecular weight (Mw) bioresorbable polymer. An ultra-high weight average molecular weight (Mw) bioresorbable polymer also degrades more slowly than a low molecular weight polymer, which means that it retains its strength longer. A stronger bioresorbable polymer enables the use of thinner struts, minimizes or eliminates vascular recoil during injury healing after deployment of the stent, and/or reduces the risk of strut fracture during stent crimping and deployment. The ultra-high weight average molecular weight (Mw) polymer makes excellent drug release barriers that are useful in producing the bioresorbable stent having controlled drug delivery. Controlling drug delivery may affect the timing of the drug release or the duration of drug delivery. Although the ultra-high weight average molecular weight (Mw) bioresorbable polymer more slowly degrades than a lower weight average molecular weight (Mw) bioresorbable polymer, the stent of the present invention has significantly less mass, which may reduce the resorption time (i.e., the time when the mass of the stent is no longer present in the treatment site). The ultra-high weight average molecular weight (Mw) bioresorbable polymer may also enable the use of bioresorbable stents in more applications such as in branched or bifurcated anatomical lumens.

The present invention of the bioresorbable stent comprises at least one layer of a therapeutic substance. The bioresorbable stent having controlled drug delivery is produced from a tube that is formed from at least one relatively long, thin film that is wrapped around the central axis of the tube multiple times in a roll configuration. The film is made by dissolving at least one bioresorbable polymer in at least one liquid solvent to form a liquid solution. Additionally, at least one active ingredient (the “drug”) may be incorporated into the liquid solution. The liquid solution is poured on a release media to form a thin liquid film on the release media, which results in a thin solid film temporarily adhered to the release media when the solvent is removed from the liquid film. The solid film is removed from the release media by peeling the solid film off the release media and organizing the solid film into a roll configuration. Alternatively, the liquid film can be directly formed in the roll configuration on a shape forming device and the solvent removed from the liquid film to form the tube. The therapeutic substance is incorporated into the tube wall thickness by positioning the therapeutic substance within at least one part of the film wall thickness or on at least one part of the outer major surfaces of the film prior to organizing the film into the shape of the roll. The very thin film thicknesses that are organized in a roll configuration are interconnected to the adjacent film thicknesses, which bonds the adjacent film thicknesses and results in a rigid tube having a solid tube wall thickness. The tube is converted into the stent by cutting a strut pattern into the tube.

The stent may include one or more coating(s) positioned on the outside surface(s) of the stent or components within the stent. The coating(s) may include one or more active ingredient(s) that are delivered within the treatment site and function as a therapeutic drug during one part of or the entire the treatment time. The coating(s) may also control or delay the degradation, corrosion, solubility, or erosion rate of the material(s) comprising the stent. The coating(s) may also increase the bond strength between the matrix and the reinforcement(s). Moreover, the coating(s) may also provide radiopacity to the stent.

The stent is delivered to the treatment site on a catheter. So that the stent can be delivered to the treatment site within the anatomical lumen, the outer diameter of the stent is temporarily reduced so that it has a low crossing profile by crimping the stent on the catheter. After crimping the stent on the catheter, the assembly is packaged, and sterilized. After delivery of the stent to the treatment site, where the catheter expands the nominal diameter of the stent from its crimped size to its deployed size, the catheter is withdrawn, and the stent temporarily supports the anatomical lumen until the treatment is completed. Preferably the implanted bioresorbable stent delivers at least one active ingredient. The degradative by-products from the stent are absorbed and/or resorbed.

Our invention provides a stent addressing the need for a better bioresorbable stent having (1) a controlled delivery of at least one therapeutic substance during at least one part of the duration that the mass of the stent is present within the anatomical lumen; (2) increased radial strength during the treatment time; (3) thinner struts to increase luminal capacity during the treatment time; (4) narrower struts to minimize anatomical lumen wall contact surface area and blockage of side artery branches; (5) thinner and/or narrower struts to improve the capability of the endothelial cells that are positioned on the inner lining of the anatomical lumen to cover the apposed struts to lower the risk of late stent thrombosis during the treatment time; (6) reduced strut fracturing; (7) improved radiopacity; (8) more controlled resorption rate; and (9) substantially complete stent mass loss to un-cage the vessel after the treatment time to partially or fully restore vasomotion and/or enable the anatomical lumen to partially or fully restore the vessel's normal capability of auto-regulating blood flow.

Accordingly, it is one object of the present invention to provide a bioresorbable film that includes or excludes at least one active ingredient.

Another object of the present invention is to provide a bioresorbable roll that includes or excludes at least one active ingredient.

One more object of the present invention is to provide a bioresorbable tube that includes or excludes at least one active ingredient.

It is an additional object of the present invention to provide a bioresorbable stent that includes or excludes at least one active ingredient.

A major object of the present invention is to provide a bioresorbable stent having a thin strut that has sufficient radial strength to support an artery opened by angioplasty balloon.

Another object of the present invention is to provide a bioresorbable stent having improved ductility to prevent the fracturing of the stent under normal operational conditions found during the delivery and/or deployment.

An object of the present invention is to provide a bioresorbable stent comprising one or more ultra-high weight average molecular weight (Mw) polymer(s).

Another object of the present invention is to provide method of forming the stent wall thickness in layers that degrade and/or resorb at different time intervals.

An object of the present invention is to include a plurality of radio dense reinforcements that make a radiopaque stent so that the stent is visible and imagable during delivery and deployment.

Finally, it is the object of the present invention to form a stent of ultra-high weight average molecular weight (Mw) raw material bioresorbable polymer(s) that results in a stent comprising post-processed polymer(s) having a weight average molecular weight (Mw) that is greater than 130 kilodaltons (kDa), 130 kilograms per mole (kg/mol) or an Inherent Viscosity that is greater than 1.3 dl/g.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specification are hereby incorporated by reference.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Overview The present invention relates to a stent10. The bioresorbable stent10is sometimes referred to in the industry as a scaffold, but for simplicity and to be consistent with historical nomenclature, the scaffold is hereinafter referred to as the “stent10”.FIG. 1depicts a perspective view of a portion of the stent10andFIG. 2depicts a cross-sectional view of the stent10depicted inFIG. 1through line A-A. The stent10is comprised of at least one stent material85, a stent outer diameter11, a stent inner diameter12, a stent wall thickness13, a stent central axis14, a stent length15, a stent outer surface16, a stent inner surface17, a stent central passageway18, a plurality of rings19, a plurality of linear ring struts20, a plurality of link struts21, a plurality of cells22, a plurality of cutting surfaces191, an inward direction23, an outward direction24, a proximal end25, and a distal end26. The rings19are arranged in series and interconnected by the link struts21.

The stent10of the present invention may be of any dimensions that meet the requirements of the end-use applications and/or treatments. Without limitation, the stent's inner diameter12may be in the range of about 1.0 millimeter (“mm”) to 30 mm and the length15may range from about 6 mm to 200 mm. In other embodiments, the stent's10inner diameter12may be equal to or less than 1 mm or equal to or greater than 30 mm to 45 mm and the stent's10length15may be equal to or less than 6 mm or equal to or greater than 200 mm to 800 mm. In the preferred embodiment the stent's wall thickness13may range from about 0.020 mm to 0.500 mm. In other embodiments, the stent's wall thickness13may be equal to or less than 0.020 mm or equal to or greater than 0.500 mm to 1.0 mm. The linear ring strut width279(depicted inFIG. 114) and the link strut width280(depicted inFIG. 114) may be in the range of about 0.030 to 0.400 mm. In other embodiments the linear ring strut width279and the link strut width280may be less than 0.030 mm or greater than 0.400 mm.

In the preferred embodiment, the stent10includes a stent-to-anatomical lumen coverage area (“STALCA”) within the range of greater than 0.0% to about less than 99.0%, more preferably in the range of about 1.0% to 45.0%, and most preferably equal to or less than about 35.0% or whatever is experimentally determined to be the optimum STALCA for the end-use application determined by those skilled in the art. For example, the STALC may be less than 10%, less than 15%, less than 20%, less than 25%, less than 30%, less than 40% or less than 50%. In other embodiments, the stent10includes a STALCA equal to or greater than 90% to 100%. The STALCA equals the surface area of the stent's40abluminal surface16area divided by the surface area of the anatomical lumen36within the treatment site.

In the preferred embodiment, the stent10or implanted stent10has a radial strength within the range of greater than 0.0 millimeters mercury (“mm Hg”) to about 1,800 mm Hg, more narrowly in the range of about 400 mm Hg to 1,800 mm Hg until the anatomical lumen36is self-supporting. In other embodiments, the stent10or implanted stent10has a radial strength equal to or above 1,800.0 mm Hg to 10,000 mm Hg. The required strength of the implanted stent10is dependent on the treatment as known by those skilled in the art of stenting.

FIG. 3depicts a non-limiting example of a Coating On Strut29. As depicted inFIG. 3, the wall thickness13of the stent10may include a coating30. The coating30may be adhered to part or all the surfaces and/or components of the stent10. For, example the coating30may be adhered to all the outer surfaces of the struts20,21as depicted inFIG. 3, on the outer surface16of the struts20,21as depicted inFIG. 4or on the outer surface16and the two cutting edges191as depicted inFIG. 5. The coating30may be adhered to the inner surface17(not depicted). In an embodiment, the stent10is a “bare” stent10, which means the stent10does not include the coating30. As depicted inFIG. 6, which is a cross sectional I view of a non-limiting example of a portion of the coating30, the coating30is comprised of a coating material31and a coating thickness33. As depicted inFIG. 7, which is a cross-sectional view of a non-limiting example of a portion the coating30, the coating30may be comprised of one or more coating layer(s)32. The coating30depicted inFIG. 7is comprised of five coating layers32, but there may be any number of coating layers32within the coating thickness33. The stent10and/or the coating30may include one or more therapeutic substances in the form of an active ingredient34, wherein one or more active ingredient(s)34means that the active ingredient34has either one chemical composition (“one active ingredient”) or multiple chemical compositions (“multiple active ingredients”). The active ingredient(s)34are depicted as black circles in the figures having the same size. The active ingredients(s)34may be other shapes and may be of different sizes in other embodiments. There may be spacing between the active ingredient(s)34, wherein the spacing is the same or different. Although the figures depict only one row of the active ingredient(s)34there may be one or multiple rows of the active ingredient(s)34. The adhered coating30may include an amorphous active ingredient34and the body of the stent10may include a crystalline active ingredient34.

The stent10wall thickness13comprises at least one layer51. In an embodiment, the stent10comprises multiple layers51as depicted inFIG. 8. Although,FIG. 8depicts five layers51, there can be up to two thousand layers51within the linear ring strut20and link strut21wall thicknesses13.

As depicted inFIG. 9,FIG. 10, andFIG. 11in an embodiment, the stent10is configured so that it may be deployed within an anatomical lumen36at a treatment site35. The treatment site35is the portion of the anatomical lumen36wherein at least one part of the outer surface16of the linear ring struts20and the link struts21contact the anatomical lumen36. In the preferred embodiment, the anatomical lumen36is a blood carrying tubular vessel or blood vessel. In other embodiments, the anatomical lumen36may be other living body parts. Without intent on limiting, the clinical need for the stent10is to help prop open the partially or fully clogged anatomical lumen36and decrease its chance of narrowing again, deliver therapeutic drugs that minimize or prevent restenosis and/or device thrombosis, and/or provide other treatments. The stent10is delivered and deployed within the anatomical lumen36at the treatment site35with a catheter37. One or more content(s)6may flow from the proximal end25to the distal end26of the stent10, or vice versa, after deployment of the stent10.

The stent10is preferably comprises an un-oriented tube42(FIG. 12) or an oriented tube38(FIG. 13).FIG. 13depicts the oriented tube38. The oriented tube38is comprised of an oriented tube outer diameter40, an oriented tube inner diameter41, an oriented tube wall thickness27, an oriented tube central axis7, an oriented tube outer surface29, an oriented tube inner surface9, an oriented tube length39and an oriented tube central passageway8.FIG. 12depicts the un-oriented tube42. The un-oriented tube42is comprised of an un-oriented tube inner diameter43, an un-oriented tube outer diameter44, an un-oriented tube wall thickness45, an un-oriented tube length46, an un-oriented tube outer surface47, an un-oriented tube inner surface48, an un-oriented tube central passageway5and an un-oriented tube central axis4.FIG. 14depicts an Un-oriented Tube Including Seam(s)49. The stent10may comprise a tube including seam(s)49. The Un-oriented Tube Including Seam(s)49is comprised of the solid film66and a seam50. The seam(s)50may be oriented perpendicular to the central axis4or at any angle to the central axis4. The seam50comprises overlapping and/or abutting film minor surfaces71that are interconnected.

In the preferred embodiment, the un-oriented tube42comprises a roll52. The roll52comprises an arrangement of at least one solid film66in a spiral configuration as depicted inFIG. 15andFIG. 16. As depicted inFIG. 15andFIG. 16, the roll52comprises a roll outer diameter54, a roll inner diameter55, a roll length56, a roll thickness57, a beginning of roll58, an end of roll59, a distance between the film thicknesses60, a roll outer surface61, a roll inner surface62, the roll passageway64, and the roll central axis63. The solid film66comprises a film thickness67, a film length68, a film width69, a film central axis70, a film long minor surface71, a film short minor surface72and a film major surface73as depicted inFIG. 17. The roll52is formed on a cylindrical-shaped shaft74as depicted inFIG. 18. In another embodiment, the solid film66comprises at least one fiber116. The shaft74comprises a shaft outer diameter75, a shaft length76, a shaft central axis77, and shaft outer surface78as depicted inFIG. 17. In an embodiment, the shaft74may also include a tapered shaft length76to facilitate removal of the un-oriented tube42from the shaft74. The film width69is generally what is needed to produce at least one stent10. The film thickness67is preferably less than 0.025 mm. In other embodiments, the film thickness67can be as thin as 0.00005 mm. However, typically the film thickness67is in the range of what is depicted inFIG. 113. The film length68can be relatively long. For example, to produce the roll52depicted inFIG. 34with a solid film66having the film thickness67equal to 0.0038 mm, the film length68is about 203 mm to produce an un-oriented tube42having a wall thickness45equal to 0.080 mm. In other embodiments, the film length68may be longer or shorter depending on the desired tube diameter, wall thickness and film thickness.

Wrapping at least one solid film66around the shaft outer surface78multiple times as depicted inFIG. 19forms the roll52. Alternatively, or additionally, wrapping multiple solid films66around the shaft74forms the roll52as depicted inFIG. 20. The film thicknesses67are interconnected at the bond65, which is positioned between each of the adjacent film thicknesses67as depicted inFIG. 21, which depicts an exploded side view of the Roll On Shaft53.FIG. 21depicts four bonds65. Depending on how many times the film(s)66are wrapped around the shaft74, in other embodiments there may be more or less bonds65required to interconnect the film thicknesses67. Interconnecting the multiple adjacent film thicknesses67converts the roll52into the solid un-oriented tube42wall thickness45. In an embodiment, the bond65comprises a bond between each of the adjacent film thicknesses67that is held together by chemical bonds such as covalent bonds, ionic bonds, polar bonds, hydrogen bonds and/or by van der Wal forces. In an embodiment, at least one of the molecule chains within the first film thickness67partially migrates into the adjacent second film thickness67by crossing the bond65and/or at least one of the molecule chains within the second film thickness67partially migrates into the adjacent first film thickness67by crossing the bond65, which interconnects the first and second film thicknesses67. Heating both the film thicknesses67and/or swelling at least one of the film thicknesses67cause the molecules within the film thicknesses67to migrate across the bond65and when the heat and/or the solvent(s)86are removed from the film thicknesses67the two adjacent film thicknesses67are interconnected. When interconnecting each of the adjacent film thicknesses67, pressure may be applied to the film thicknesses67when they are being heated and/or cooled to form the interconnection. Pressure may also be exerted on the bond65when the solid film(s)66shrink onto the shaft when heated and/or cooled. It should be appreciated that even thoughFIG. 19,FIG. 20,FIG. 33,FIG. 35,FIG. 37,FIG. 39,FIG. 41,FIG. 43,FIG. 45,FIG. 47,FIG. 48,FIG. 50,FIG. 51,FIG. 53,FIG. 55,FIG. 57,FIG. 59,FIG. 62,FIG. 63,FIG. 64,FIG. 65,FIG. 66andFIG. 67depict the solid films66being wrapped around the shaft74when the solid film(s)66are in the horizontal position that the solid films66may be wrapped around the shaft74when the solid film(s)66are in the vertical position or any position in between horizontal and vertical.

FIG. 21depicts a Roll On The Shaft53. As depicted inFIG. 21, wrapping at least one solid film66around the shaft74forms the roll52. Alternatively, The Roll On Shaft53may comprise at least one film66, a laminate100, a fibrous sheet108, an Infused Fibrous sheet126, a Fiber reinforced Laminate130, or any combinations thereof. After the roll52is converted into the un-oriented tube42, the Beginning Of The Roll58is located closer to the inner surface48and the End Of The Roll59is located closer to the outer surface47of the roll52that is formed into the unoriented tube42, which is converted into the oriented tube38and/or the stent10. As depicted inFIG. 22, which is a portion92of the roll52depicted inFIG. 21, once each additional wrap crosses over the point where the previous wrap was completed an Over-Film Thickness93is formed on top of the Under-Film Thickness94. Still referring toFIG. 22, when each wrap is completed the solid film66forms an abrupt transition95where the distance from the shaft74outer surface78is greater for the Over-Film Thickness93than the Under-Film Thickness94. The solid film66forms an abrupt transition95because there is an immediate change in the diameter of the underlying surface when the solid film66being laid down rides over the film thickness67of the previously laid down solid film66or the Under-Film. Therefore, each film thickness67gets farther away from the shaft outer surface78as it is laid down on the previous film thickness67. As previously mentioned,FIG. 21depicts the film thicknesses67of the solid film66in an exploded view where there is the separation distance60between the Under-Film and the shaft74and the separation distance60between the Under-Film Thickness94and the Over-Film Thickness93to make it easier to visualize the spiral configuration of the solid film66within the roll52. In the preferred embodiment, there is no separation distance60or very little separation distance60between the film thicknesses67. In other embodiments of the roll52, there may be some separation distance(s)60.

FIG. 23depicts a Deposited Solution82. The solid film66is formed by depositing a liquid solution83on a release media84as depicted inFIG. 23. Provisional Patent Application Ser. No. 62/443,101 filed Jan. 6, 2017; entitled “ANISIOTROPIC BIORESORBABLE STENT FORMED FROM INTERCONNECTED LAYERS OF HIGH MOLECULAR WEIGHT ISOTROPIC FILM” provides additional information about producing solid films66and forming the solid films66into the stent10, which is incorporated herein as a reference. The release media84may be, for example, comprised of polyethylene sheet or the like. The liquid solution83is comprised of at least one stent material85and at least one liquid solvent86. The liquid solution83may be comprised of between greater than 0 wt. % to 35 wt. % stent material(s)85and the remainder of the liquid solution83that has a total wt. % of 100% is solvent(s)86and/or the active ingredient(s)34. In other embodiments, the liquid solution83comprises equal to or greater than 35 wt. % stent material(s)85and the remainder is solvent(s)86and/or active ingredient(s)34. In an embodiment the liquid solution83has a viscosity within the range of greater than 3.0.times.10.sup.-4 Pa-S to 50.0 Pa-S, more narrowly less than 3 Pa-S, at approximately the time of placement of the liquid solution83on the release media84. Depositing the liquid solution83on the release media84forms a liquid film87having a liquid film thickness88and a liquid film width89. After deposition, the liquid solvent86is removed by, for example, evaporation or vaporization of the liquid solvents86within a gaseous medium90leaving the solid film66, which is substantially comprised of the stent material85, on the release media84. The solid film66is comprised of the solid film thickness67and the solid film width69. The solid film66is removed from the release media84by pealing the solid film66off the release media84to form the roll52that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. A device may be used to control static build up on the solid film66. The solid film66formed on the release media84is generally amorphous having a crystallinity between 0% to 25%, more narrowly less than 15%. The solid film66of the present invention is unique because it shrinks when heated and/or cooled. It is believed that the solid film(s)66shrink when they are heated and/or cooled because the solid film(s)66are being converted from a more amorphous state to a more crystalline state during the thermal cycle, wherein the crystalline portions of the solid film(s)66fold and take up less space, which results in shrinkage.

The solid film66may include molecular orientation that is imparted on the solid film66when it is dry or swollen by stretching in the solid film66in a machine direction79, a transverse direction80or a biaxial direction81, which is a combination of machine direction and transverse direction prior to or during forming of the solid film66into the un-oriented tube42or the oriented tube38, which are converted into the stent10. A dry solid film66means that the solvent86is completely removed from the solid film66, which results in the solid film66comprising only the stent material(s)85or all stent material(s)85and/or the active ingredient(s)34except for a small residual amount of the solvent(s)86equal to or less than 0.01 wt. % solvent(s)86. The swollen solid film66means the solid film66comprises the stent material(s)85and/or the active ingredient(s)34and at least one part solvent(s)86. It is believed that it is easier to obtain molecular orientation of the molecular chains within the stent material(s)85in the direction of strain in a swollen solid film66than a dry solid film66because the chains have fewer entanglements, which allow the chains to more easily slip by each other when the solid film66is strained. The swollen solid film66may be formed by not allowing the liquid film78to completely dry.

The swollen solid film66, wherein the swollen solid film66has constituents equal a total of 100 wt. %, preferably comprises between equal to 0.01 wt. % to 65 wt. % solvent(s)86and the remainder of the swollen solid film66comprises the stent material(s)85and/or the active ingredient(s)34. In other embodiments, the swollen solid film66comprises greater than 65 wt. % to 99 wt. % solvent(s)86and the remainder comprises the stent materials(s)85and/or the active ingredient(s)34. A swollen solid film66that contains solvent(s)86are useful for interconnecting the film thicknesses67without heating the roll52. The swollen solid film66interconnects with other swollen solid film(s)66and/or other dry solid film(s)66when they are adjacently positioned within the roll52and/or Roll Including Active Ingredient(s)143. As the swollen film66dries some of the solvent(s)86within the swollen solid film66migrates into the adjacent solid film66, which allows the molecules to bridge the bond65and form a solvent bond between the two film thicknesses67as the films dry to form the un-oriented tube42and/or the oriented tube38. Alternatively, or additionally, the dry solid film66is converted into the swollen solid film66or the swollen solid film66is made more swollen by adding more solvent(s)86to the dry or swollen solid film66.

In an embodiment, stretching the swollen, solid film66results in a Swollen Film Transverse Widening Ratio (“SFTWR”) between greater than 0.0 to 10.0. In other embodiments the SFTWR is equal to or greater than 10.0. The SFTWR equals the swollen solid film's width69after widening divided by the swollen solid film's width69prior to widening. In an embodiment, stretching the swollen, solid film66results in a Swollen Film Axial Elongation Ratio (“SFAER”) between greater than 0.0 to 10.0. In other embodiments, the SFAER is equal to or greater than 10.0. The SFAER equals the swollen solid film's length68after elongating divided by the swollen solid film's length68prior to elongating. The SFAER to SFTWR ratio equals the SFAER divided by the SFTWR. In an embodiment, the SFAER to SFTWR ratio is equal to 1.0 to 10.0. In other embodiments, the SFAER to SFTWR ratio is equal to or greater than 10.0 or equal to or less than 1.0.

In an embodiment, stretching the swollen, solid film66results in a Swollen Film Draw Down Thickness (“SFDDT”) between 0.0 and 10.0. In other embodiments the SFDDT is equal to or greater than 10.0. The SFDDH equals the average film thickness67of the swollen solid film66before stretching divided by the average film thickness67of the swollen solid film66after stretching. In an embodiment, stretching the swollen, solid film66results in a Swollen Film Draw Down Width (“SFDDW”) between 0.0 and 10.0. In other embodiments the SFDDW is equal to or greater than ten 10. The SFDDW equals the nominal width69of the swollen solid film66before stretching divided by width69of the swollen solid film66after stretching. Swollen solid film(s)66wrapped around the shaft74may interconnect with or without heating the solid film(s)66on the shaft74. In an embodiment, solvent bonding interconnects the film thicknesses67of the swollen solid film(s)66. In another embodiment, solvent bonding interconnects the substantially dry solid film(s)66.

The solid film66may include the active ingredient(s)34or exclude the active ingredient(s)34. The active ingredient(s)34may be positioned within the solid film66by incorporating the active ingredient(s)34into the liquid solution83prior to depositing the liquid solution83on the release media84. The active ingredient(s)34are preferably incorporated into the liquid solution83within greater than 0 seconds to 60 minutes before depositing the liquid solution83including the active ingredient(s)34on the release media84. In other embodiments, the active ingredient(s)34may be incorporated into the liquid solution83between at least one of the following timeframes before depositing the liquid solution83including the active ingredient(s)34on the release media84: (1) greater than 0 seconds to 2 hours, (2) greater than 0 seconds to 3 hours, (3) greater than 0 seconds to 4 hours, (4) greater than 0 seconds to 5 hours, (5) greater than 0 seconds to 6 hours, (6) greater than 0 seconds to 7 hours, (7) greater than 0 seconds to 8 hours, (8) greater than 0 seconds to 24 hours, (9) greater than 0 seconds to 7 days, (10) greater than 0 seconds to 1 month, or (11) greater than 0 seconds to 1 year. In still another embodiment, the active ingredient(s)34may be incorporated into the liquid solution83between greater than 0 seconds to 10 years before depositing the liquid solution83including the active ingredient(s)34on the release media84. Alternatively, or additionally, the active ingredient(s)34may be added to the solvent(s)86prior to adding the stent material(s)85when preparing the liquid solution83.

In an embodiment, the solid film66, the roll52, the un-oriented tube42and/or the oriented tube38include at least one part or entirely crystalline or amorphous sirolimus, crystalline or amorphous everolimus, crystalline or amorphous biolimus, crystalline or amorphous corolimus, crystalline or amorphous ridaformolimus, crystalline or amorphous umirolimus, crystalline or amorphous myolimus, crystalline or amorphous novolimus, crystalline or amorphous zotarolimus, and other crystalline or amorphous macrolide immunosuppressant's or other crystalline or amorphous inhibitors of neointimal growth, wherein crystalline means the active ingredient34has a degree of crystallinity ranging from 50 to 100% and amorphous means an active ingredient34having a degree of crystallinity ranging from 0 to less than 50%.

FIG. 24depicts the film66excluding the active ingredient(s)34. In this embodiment, the film66may be formed into the roll52to provide strength to the wall thickness13of the stent10. Alternatively, or additionally, the film66excluding the active ingredient(s)34may be used as a barrier layer51to control the timing of the release and/or the rate release of the active ingredient(s)34, which may be referred to as a barrier layer51herein.FIG. 25depicts the film66including the active ingredient(s)34, which may be referred to as a therapeutic layer51within this specification. In this embodiment, the film66may be formed into the roll52to provide a therapeutic layer51that releases at least one or all the active ingredient(s)34during the treatment time. Additionally, the film66including the active ingredient(s)34may change the mechanical properties of the stent10by, for example, stiffening the stent10with a material that has a higher elastic modulus than the stent material(s)85comprising the remainder of the film66.FIG. 26depicts a laminate100comprising the active ingredient(s)34positioned between two active ingredient-free films66. In this embodiment, the roll52comprising the laminate66provides strength to the thickness of the stent10and provides controlled delivery of the active ingredient(s)34when the stent10is implanted within the anatomical lumen36.

Alternatively, or additionally, the stent10, the roll52, the unoriented tube42, and/or the oriented tube38may at least partially or completely comprise a laminate100.FIG. 27depicts the laminate100. The laminate100may be wrapped around the shaft74to form the roll52that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. The laminate comprises the solid film66superimposed with at least one other solid film66to form the laminate100. In an embodiment, there may be at least one active ingredient34within the laminate100. The laminate100is comprised of a laminate thickness101, a laminate width102, a laminate length103, a laminate major surface104, a laminate long minor surface106, a laminate short minor surface105, and a laminate lengthwise axis107. The roll52or the Roll Including Active Ingredient(s)143may comprise superimposed solid films66that are interconnected or disconnected within the roll52or the Roll Including Active Ingredient(s)143, the un-oriented tube42, the oriented tube38and/or the stent10. The bond65may interconnect the solid film(s)66within the laminate100before or after formation of the roll52. Alternatively or additionally, laminate100may comprise the at least one swollen, solid film66between two dry, solid films66, wherein the residual solvent86within the swollen solid film66creates a solvent weld between the dry solid films66that interconnects the films66as the solvent86evaporates or vaporizes during drying of the laminate100and/or the un-oriented tube42. Moreover, the laminate100may include molecular chain orientation that is imparted on the laminate100when the solid film(s)66are dry or swollen by stretching in the laminate100in the machine direction79, the transverse direction80or the biaxial direction81prior to or during formation of the roll52or the Roll Including Active Ingredient(s)143that is formed into the oriented tube38and/or the stent10.

FIG. 28depicts a fibrous sheet108. Alternatively, or additionally, the stent10may include at least one fibrous sheet108. The fibrous sheet108may be wrapped around the shaft74by itself or with at least one solid film66to form the roll52or the Roll Including Active Ingredient(s)143that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. The fibrous sheet108is comprised of a fibrous sheet thickness109, a fibrous sheet width110, a fibrous sheet length111, a fibrous sheet major surface112, a fibrous sheet long minor surface114, a fibrous sheet short minor surface113, and a fibrous sheet lengthwise axis115. Moreover, the fibrous sheet108may include molecular chain orientation that is imparted on the fibrous sheet108when it is dry or swollen by stretching in the fibrous sheet108in the machine direction79, the transverse direction80or the biaxial direction81prior to or during formation of the roll52or the Roll Including Active Ingredient(s)143that is formed into the oriented tube38and/or the stent10.

The fibrous sheet108is comprised of at least one fiber116and/or at least one multi-fiber117, which are depicted inFIG. 29andFIG. 30, respectively. The fiber116is comprised of a fiber thickness118, a fiber length119, a fiber lengthwise axis120and a fiber outer surface121. The multi-fiber117is comprised of a multi-fiber thickness122, a multi-fiber length123, a multi-fiber lengthwise axis124and a multi-fiber outer surface125. The fibers116within the multi-fiber117may be twisted, knitted or braided. The fibrous sheet108may be converted into an Infused Fibrous Sheet126. As depicted inFIG. 31, the Infused Fibrous Sheet126is comprised of at least one fiber116and/or multi-fiber117, a plurality of void spaces127positioned between the fiber(s)116and/or the multi-fiber(s)117, a plurality of nodes128positioned where the fiber(s)116and/or the multi-fiber(s)117intersect or cross over, and a matrix129. The matrix129, which is at least partially or completely comprised of the stent material(s)85, partially or completely fills the void spaces127, which are located between the fiber(s)116and/or multi-fiber(s)117. In an embodiment, the fiber116and/or the multi-fiber108may include the active ingredient(s)34. The matrix129may be positioned within the void spaces127by infusing the liquid solution83into the void spaces127one or more times and removing the liquid solvent(s)86from the matrix129. For example, the liquid solution83may be poured onto the fibrous sheet108so that the void spaces127are at least partially filled with liquid solution83. When the solvent(s)86within the liquid solution83are removed from the liquid solution83, the stent material85remains within the void spaces127forming the matrix129between the fiber(s)116and/or multi-fibers117. The surface121,125modification may improve the process of infusing the fibrous sheet108by increasing the adhesion between the matrix129and the fiber116or multi-fiber117by improving the way the liquid solution83wets out the fibrous sheet108. The surface121,125modification may improve the ability of the liquid solution83to penetrate into the plurality of void spaces127positioned within the wall thickness109of the fibrous sheet108. The liquid solution83used to infuse the fibrous sheet108comprises the at least one stent material85and at least one solvent86that does not dissolve the fiber(s)116and/or multi-fiber(s)117when the liquid solution83contacts the fiber(s)116and/or the multi-fibers117. The matrix129and/or the void space127may include at least one active ingredient34.

Imparting changes in the properties of the surface(s)9,16,17,29,47,48,61,62,71,72,73,78,104,105,106,121,125,191using a high frequency corona discharge or air plasma techniques may modify at least one of the surfaces. In other embodiments, some or all the surface(s)s may be modified by imparting changes in the properties of the surface(s) using atmospheric plasma treatment, flame plasma, or chemical plasma. The modification technique may change the surface energy of at least one of the stent material(s)85within the stent10or the stent's10components. Modifications to some or all the surface(s) within the stent10or the stent's components, for example, may improve adhesion to the other solid film(s)66, fiber(s)116, multi-fiber(s)117, layer(s)51, laminate(s)91, fibrous sheet(s)102, infused fibrous sheet(s)120, fiber-reinforced laminate(s)130, coating(s)30, or other materials. The surface modification(s) may also improve biocompatibility of the stent10after deployment of the stent10within the anatomical lumen36.

At least one of the surface(s) may be modified with acid; sulfuric acid; potassium chlorate; hydrochloric acid; ultraviolet light; ozone; chromic acid; formalin-fixed paraffin-embedded (FFPE) modification; agents that generate oxygen in the form of hydroxyl; agents that produce hydroxyl, aldehyde, carboxyl, or other enhancing groups on the surface; agents that modify the carbon/oxygen ratio of the surface(s); agents that create at least one charged groups that are anions; agents that modify the surface with at least one cation; serum; protein; oxidizing agent; oxygen plasma; silanization; radiation or combinations thereof. Without intent on limiting, in other embodiments, the modification(s) include modifying the surface tension, surface energy, increasing or decreasing the surface charge density, charge, hydrophobicity, hydrophilicity, wettability, polylysine coating, agents that enhance cell or tissue culture growth, or any combinations thereof.

The fibrous sheet108and/or the infused fibrous sheet126may be incorporated into the laminate100to form a Fiber-reinforced Laminate130as depicted inFIG. 32. Alternatively, or additionally, the stent10includes the Fiber-reinforced laminate130. The Fiber-reinforced Laminate130may be wrapped around the shaft74by itself or with at least one solid film66to form the roll52that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. The Fiber-reinforced Laminate130is comprised of a fiber-reinforced laminate height131, a fiber-reinforced laminate width137, a fiber-reinforced laminate length132, a fiber-reinforced laminate major surface133, a fiber-reinforced laminate long minor surface135, a fiber-reinforced laminate short minor surface134, and a fiber-reinforced laminate lengthwise axis136. The superimposed solid film(s)66, the fibrous sheet108, and/or the infused fibrous sheet126that are within the Fiber-reinforced Laminate130may be interconnected or disconnected prior to forming the Fiber-reinforced Laminate130into the roll52and/or the Roll Including Active Ingredient(s)143that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. The knit line65may interconnect the solid film(s),66, the fibrous sheet(s)108and/or the infused fibrous sheet126that are within the Fiber-Reinforced Laminate130before or after forming the solid film(s),66, the fibrous sheet(s)108and/or the infused fibrous sheet126into the roll52. Moreover, the Fiber-reinforced Laminate130may include molecular chain orientation that is imparted on the Fiber-reinforced Laminate130when it is dry or swollen by stretching in the Fiber-reinforced Laminate130in the machine direction79, the transverse direction80or the biaxial direction81prior to or during formation of the roll52or the Roll Including the Active Ingredient(s)143that is formed into the oriented tube38, which is converted into the stent10.

FIG. 33depicts an Indirect Roll Formation Process138. The Indirect Roll Formation Process138forms the Roll52. As depicted inFIG. 33, the Indirect Roll Formation Process138comprises the shaft74, at least one solid film66and a Film Rotation Direction139. As depicted inFIG. 19andFIG. 33, the roll52is formed by positioning The Beginning Of The Roll58in contact with the Shaft Outer surface78and wrapping the solid film66around the shaft74in the Film Rotation Direction139until the entire length68of the solid film66encircles the shaft74. The Film Rotation Direction139can be clockwise or counterclockwise. It is also possible to roll the cylindrical-shaped shaft74over the solid film(s)66to wrap the solid film(s)66around the shaft74. The Indirect Roll Formation Process138forms the roll52depicted inFIG. 34. AlthoughFIG. 34depicts the solid film66wrapped around the shaft74five times, it is possible in other embodiments to wrap the solid film66around the shaft74between 2 to 2,000 times by increasing the length68of the solid film66. The length68of the solid film68may range from about 3 mm to 8,000 cm. In other embodiments, the length69of the solid film66is longer or shorter. In other embodiments, the solid film66is wrapped around the shaft equal to or greater than 2,000 times. Once part or all of the length68of the solid film66is wrapped around the shaft74, the End Of The Roll59or anywhere between the Beginning Of The Roll58and/or the End Of The Roll59may be secured to the Under-Film Thickness94to prevent the roll52from unwinding. Although the figures depict the Beginning Of The Roll58and the End Of The Roll59starting and ending at the same circumferential position on the roll52(e.g., at 90 degrees), in other embodiments the Beginning Of The Roll58and the End Of The Roll59may be positioned at different circumferential positions (anywhere from 0 to 360 degrees). For example, the Beginning Of The Roll58may be positioned at 270 degrees and the End Of The Roll59may be positioned at 90 degrees. The Indirect Roll Formation Processes138and the rolls52depicted in the figures are shown in exploded view to clearly illustrate the configuration of the solid film(s)66within the roll52that is formed into the unoriented tube42, which is converted into the oriented tube38and/or the stent10. It should be appreciated that the separation distance60ideally equals 0.000 mm or is substantially nonexistent in the actual roll52and that the Over-Film Thicknesses93lie directly on the Under-Film Thicknesses94without any space between the film thicknesses67. Alternatively, or additionally, the Indirect Roll Formation Process138may form at least one of the laminate100, the fibrous sheet108, the infused fibrous sheet126and/or the Fiber-reinforced Laminate130into the roll52.

Alternatively, as depicted inFIG. 20andFIG. 35, wrapping two partially or completely superimposed solid films66around the shaft74forms the roll52that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10.FIG. 35depicts the Indirect Roll Formation process138, wherein the solid film66-B is completely superimposed on solid film66-A.FIG. 39depicts the Indirect Roll Formation Process138, wherein the solid film66-B is partially superimposed on solid film66-A. In an embodiment, the solid film66-A and solid film66-B, depicted inFIG. 20andFIG. 35, may comprise the same stent material(s)85. In other embodiments, the solid film66-A and solid film66-B, depicted inFIG. 20andFIG. 35may comprise different stent materials85. In an embodiment, the solid film66-A has the same film thickness67as solid film66-B. In another embodiment, the solid film66-A has the film thickness67greater than the solid film66-B. In yet one more embodiment, the solid film66-B has the film thickness67greater than the solid film66-A. It should be appreciated that the film thicknesses67of all embodiments are within the film thickness67limitations provided within this specification, more narrowly within the specifications provided inFIG. 113. The Roll Formation Process138depicted inFIG. 35produces the roll52depicted inFIG. 36. As depicted inFIG. 35, the roll52is formed by positioning The Beginning Of The Roll58in contact with the Shaft Outer surface78and wrapping the solid films66around the shaft74in the Film Rotation Direction139until the entire length68of the solid films66encircle the shaft74. Since the roll52depicted inFIG. 36includes two solid films66, the films66may be wrapped around the shaft74between 2 to 1000 times to produce the roll52that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. In other embodiments, the roll52comprising two solid films66are wrapped around the shaft74equal to or greater than 1000 times. When the roll52comprises at least two solid films66comprising two different stent material(s)85, two discrete layers51are formed within the un-oriented tube42. The layers51are discrete because when the film thicknesses67within the roll52are interconnected during conversion of the roll52into the un-oriented tube42there is very little or no mixing of the stent material(s)85comprising the adjacent layers51at the bond65, which results each layer51substantially retaining its unique composition after the interconnection is made. As depicted inFIG. 36, when looking at the roll52in exploded cross-sectional view, in an embodiment wherein the stent material(s)85comprising the solid film66-A are different than the stent material(s)85comprising the solid film66-B, a layer thickness91is formed within the roll52, wherein the solid film66-A forms a layer thickness91-A and the solid film66-B forms a layer thickness99-B. In an embodiment wherein the stent material(s)85comprising the solid film66-A and the solid film66-B are the same, there is one layer91formed. One method of observing the discrete layers within the stent10wall thickness13is to examine the cross-section of the stent10wall thickness13with an optical microscope using cross-polarized light. DuPont Engineering Polymers Failure Analysis Using Microscopic Techniques authored by Edith Bohme provide techniques for examining the layers51.

AlthoughFIG. 36shows superimposed solid film66-A and solid film66-B being wrapped around the shaft74three times, the superimposed solid film66-A and solid film66-B can be wrapped around the shaft74more than three times by increasing the length68of the solid film66-A and the solid film66-B. It should be appreciated, that the pattern of the solid film66-B being positioned near the inner surface62of the roll52and the solid film66-A positioned on the outer surface61of the roll52may be reversed so that solid film66-A is on the inner surface62and solid film66-B is on the outer surface61. In the preferred embodiment, the pattern of two alternating films66that is depicted inFIG. 36and its variants may be repeated within the roll thickness57between 1 to 1000 times. In other embodiments, the pattern of two alternating solid films66that are depicted inFIG. 36and its variants may be repeated within the roll thickness57equal to or greater than 1000 times.

In another embodiment, as depicted inFIG. 37, wrapping three partially or fully superimposed solid films66around the shaft74forms the roll52that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. In an embodiment, all the solid films66-A, solid film66-B and solid film66-C depicted inFIG. 37comprise the same stent material(s)85. In other embodiments, at least one or all of the solid film66-A, solid film66-B and solid film66-C depicted inFIG. 37may comprise different stent material(s)85. When the solid film66-A comprises a different stent material85than solid film66-B and solid film66-C, solid film66-B comprises different stent material85than solid film66-A and solid film66-C and solid film66-C comprises different stent material85than solid film66-A and solid film66-B, three different layers51are formed within the stent10wall thickness13, which have a layer thickness91-A, layer thickness91-B and layer thickness91-C. In an embodiment, two of the layers51comprise the same stent material85and one layer51comprises a different stent material85, wherein the layer51comprising the different stent material85separates the two layers comprising the same stent material85. In an embodiment, the solid film66-A has the same film thickness67as solid film66-B and solid film66-C. In other embodiments, at least one of the solid films66within the embodiment depicted inFIG. 37is larger than at least one or all the other solid film66. It should be appreciated that the film thicknesses67of all embodiments are within the film thickness67limitations provided within this specification, more narrowly within the film thickness67limitations provided inFIG. 113.

The Roll Formation Process138depicted inFIG. 37produces the roll52depicted inFIG. 38. As depicted inFIG. 37, the roll52is formed by positioning The Beginning Of The Roll58, which comprises three solid films66, in contact with the Shaft Outer surface78and wrapping the superimposed solid film66-A, solid film66-B and solid film66-C around the shaft74in the Film Rotation Direction139until the entire length68of the solid films66encircle the shaft74. The solid film66-A may be connected to the solid film66-B and solid film66-A may be connected to solid line66-C with the bond65prior to wrapping the solid films66around the shaft74. In other embodiments, solid film66-A, solid film66-B and solid film66-C may be disconnected prior to wrapping the solid films66around the shaft. Since the roll52depicted inFIG. 38includes three solid films66, the superimposed films66may be wrapped around the shaft74between 1 to 334 times to produce the roll52, which is converted into the un-oriented tube34. In other embodiments, the roll52comprising three solid films66are wrapped around the shaft74equal to or greater than 334 times. The pattern of three alternating films66that is depicted inFIG. 36and its variants may be repeated within the roll thickness57between 1 to 334 times. In other embodiments, the pattern of two alternating films that is depicted inFIG. 36and its variants may be repeated within the roll thickness57equal to or greater than 334 times. It should be appreciated that it is possible for the position of solid film66-A, solid film66-B and solid film66-C to be positioned differently that what is shown inFIG. 37, wherein solid film66-C is positioned on the bottom, solid film66-B is positioned in the middle and solid film66-A is positioned on the top of the stack of the superimposed films66. For example, where the position of the solid film66within the stack of superimposed films66is (top, middle, bottom), each solid film66may alternatively have the position within the stack of the superimposed solid films66depicted inFIG. 37in one of the following configurations: (66-A,66-C,66-B) or (66-B,66-A,66-C) or (66B,66-C,66-A) or (66-C,66-B,66-A) or (66-C,66-A,66-B).

AlthoughFIG. 37andFIG. 38depict three completely superimposed solid film(s)66, in other embodiments there may be more than three completely superimposed solid film(s)66wrapped around the shaft74to form the roll52that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. The maximum number of solid films66that may be incorporated into the roll52depends on the practical limit of the un-oriented tube wall thickness45, the number of wraps of the solid films66around the shaft74and the film thickness67limitations provided within this specification, more narrowly the film thicknesses67provided inFIG. 113. When there are greater than three solid films66incorporated into the roll52, each of the solid films66may comprise the same stent material(s)85or at least one or all of the solid film(s)66may comprise different stent material(s)85. The solid film66-A may be connected or disconnected to the solid film66-B and the solid film66-B may be connected or disconnected to solid film66-C and so on with the bond65prior to wrapping the solid films66around the shaft74. The pattern of greater than three alternating films66(not depicted) may be repeated within the roll thickness57equal to between 1 time to 1000 times divided by the number of the superimposed films66. In other embodiments, the pattern of greater than three alternating solid films66may be repeated within the roll thickness57the number of times that is equal to or greater than 1000 times divided by the number of superimposed solid films66. It is believed that between 2 to 500 separate solid films66may be at least partially or completely superimposed prior to wrapping the superimposed solid films66around the shaft74to form the roll52that forms the un-oriented, which is converted into the oriented tube38and/or the stent10. In other embodiments, there may be equal to or greater than 500 separate solid films66at least partially or completely superimposed prior to wrapping the superimposed solid films66around the shaft74to form the roll52.

In another embodiment, as depicted inFIG. 39, wrapping two partially superimposed solid films66around the shaft74forms the roll52that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10.FIG. 39depicts one long solid film66-B that is partially superimposed one short solid film66-A. The roll52is formed by positioning the Beginning Of The Roll58of solid film66-B on the shaft outer surface78, partially wrapping the solid film66-B around the shaft74until solid film66-A is near the shaft74and then wrapping the solid film66-B and the solid film66-A around the shaft74until the entire length68of the solid film66-B and the solid film66-A are wrapped around the shaft74. The Indirect Roll Formation Process138depicted inFIG. 39results in the roll52depicted inFIG. 40. It should be appreciated that the solid film66-A may be positioned on top of the solid film66-B. Moreover, the solid film66-A may be positioned near the Beginning Of The Roll58instead of the middle of the roll and/or near the End Of The Roll59instead of the middle of the roll. In other embodiments, the solid film66-A may be positioned on either the top and/or the bottom of the solid film66-B. Furthermore, it should be appreciated that althoughFIG. 39depicts that the film66-A covers about 50% of the length68of the solid film66-B that in other embodiments the solid film66-A covers greater than or less than 50% of the length68of the solid film66-A. The solid films66depicted inFIG. 39andFIG. 40may have the same film thickness67or different film thicknesses67. For example, solid film66A may be thicker than solid film66-B or the opposite. The solid films66-A and solid film66-B, depicted inFIG. 39andFIG. 40, may comprise the same stent material(s)85or comprise different stent materials85. When solid film66-A comprises a different stent material85than solid film66-B, the layers51are formed, which have the layer thickness91-A and layer thickness91-B. Moreover, thoughFIG. 40depicts in exploded cross sectional view that the solid film66-B forms one complete wrap and solid film66-B forms three complete wraps, in other embodiments solid film66-B and/or solid film66-A may form a greater or lesser amount of wraps than what is shown in the figures or at least one of the wraps may incompletely surround the circumference of the roll52. Additionally, it should be appreciated that there may be greater than one long solid film66and greater than one short film66positioned within the roll52and that the long films66may be of the same or different lengths68and the short films66may be of the same or different lengths68.

In another embodiment of the Indirect Roll Formation Process138, as depicted inFIG. 41, wrapping two different solid films66that are positioned in series around the shaft74forms the roll52that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10.FIG. 41depicts solid film66-A being wrapped around the shaft74first and solid film66-B being wrapped around the shaft74second. The Roll Formation Process138depicted inFIG. 41produces the roll52depicted inFIG. 42. The solid film66-A may be connected to the solid film66-B with an optional splice147prior to wrapping the solid films66around the shaft74, wherein the splice147that connects the two solid film(s)66may be abutting or overlapping. Alternatively, the solid films66-A and66-B may be disconnected prior to wrapping the solid films66around the shaft74so that each separate solid film66is individually wrapped around the shaft74. The solid films66depicted inFIG. 41andFIG. 42may have the same film thickness67or different film thicknesses67. For example, solid film66-A may be thicker than solid film66-B or the opposite. The solid films66-A and solid film66-B, depicted inFIG. 41andFIG. 42, may comprise the same stent material(s)85or comprise different stent materials85. When solid film66-A comprises a different stent material85than solid film66-B, the layers51are formed, which have the layer thickness91-A and layer thickness91-B. AlthoughFIG. 42depicts the solid film66-A and solid film66-B being wrapped around the shaft74two times, the solid film66-A may be wrapped around the shaft74greater than or less than two times and solid film66-B may be wrapped around the shaft74greater than or less than two times by increasing or decreasing the length68of the solid film66-A and the solid film66-B. Moreover, althoughFIG. 42depicts that solid film66-A and solid film66-B are both are wrapped around the shaft74the same number of times, in other embodiments solid film66-A may be wrapped around the shaft74greater or lesser times than solid film66-B. It should be appreciated, that the pattern of the solid film66-A being positioned near the inner surface62of the roll52and the solid film66-B on the outer surface61may be reversed so that solid film66-B is on the inner surface62and solid film66-A is on the outer surface61. It is also possible that the roll thickness57pattern shown inFIG. 42, wherein there are two film thicknesses67comprising solid film66-A and two film thicknesses67comprising solid film66-B, may be repeated multiple times until the roll thickness57reaches a dimension that is suitable for producing the unoriented tube42. For example, and without intent on limiting, the roll thickness57may include the pattern starting from the roll inner surface62to the roll outer surface61comprising: (1) two film thicknesses67comprising solid film66-A and two film thicknesses67comprising solid film66-B; (2) two film thicknesses67comprising solid film66-A and two film thicknesses67comprising solid film66-B (“first repeat”); (2) two film thicknesses67comprising solid film66-A and two film thicknesses67comprising solid film66-B (“2nd repeat”) and (4) so on until the desired roll thickness57is achieved, or the opposite. To repeat the pattern in the embodiment depicted inFIG. 43, one additional solid film66-A and one additional solid film66-B must be added to the roll depicted inFIG. 42to produce the 1st repeat and one additional solid film66-A and one additional solid film66-B must be added to the roll depicted inFIG. 42to produce the 2nd repeat. The pattern depicted inFIG. 41andFIG. 42may be repeated between 1 to 500 times. In other embodiments of the roll52configuration having two different solid films66positioned in series in a repeating pattern may be repeated equal to or greater than 500 times.

In yet one more embodiment of the Indirect Roll Formation Process138, as depicted inFIG. 43, wrapping at least three different solid films66that are positioned in series around the shaft74forms the roll52that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10.FIG. 43depicts solid film66-A being wrapped around the shaft74first, solid film66-B being wrapped around the shaft74second and solid film66-C being wrapped around the shaft74third. The Roll Formation Process138depicted inFIG. 43produces the roll52depicted inFIG. 44. The solid film66-A may be connected to the solid film66-B and solid film66-B may be connected to solid film66-C with the optional splice147that interconnects the solid films66prior to wrapping the solid films66around the shaft74, wherein the splice147may be the abutting or overlapping. Alternatively, the solid films66-A,66-B and66-C may be disconnected prior to wrapping the solid films66around the shaft74so that each individual solid film66is wrapped around the shaft74sequentially. The solid films66depicted inFIG. 43andFIG. 44may have the same film thickness67or different film thicknesses67that are within the limitations provided within this specification, more narrowly within the specifications provided inFIG. 113. For example, solid film66-A may be thicker than solid film66-B and solid film66-C, solid film66-B may be thicker than solid film66-A and solid film66-C or solid film66-C may be thicker than solid film66-A and solid film66-B. In other embodiments, there may be any combinations or permutations of film thicknesses67that are selected from the limitations provided within this specification, more narrowly the specifications provided inFIG. 113, that may be incorporated into the roll52, wherein the film thicknesses67are selected from the group of: (1) F-A is thinnest, (2) F-A is second thinnest, (3) F-A is third thinnest, (4) F-A is thickest, (5) F-A is second thickest, (6) F-A is third thickest, (7) F-B is thinnest, (8) F-B is second thinnest, (9) F-B is third thinnest, (10) F-B is thickest, (11) F-B is second thickest, (12) F-B is third thickest, (13) F-C is thinnest, (14) F-C is second thinnest, (15) F-C is third thinnest, (16) F-C is thickest, (17) F-C is second thickest or (18) F-C is third thickest; wherein “F-A” refers to solid film66-A, “F-B” refers to solid film66-B and “F-C” refers to solid film66-C.

In an embodiment, all the solid films66-A, solid film66-B and solid film66-C depicted inFIG. 43andFIG. 44may comprise the same stent material(s)85. In other embodiments, at least one or all the solid film66-A, solid film66-B and solid film66-C depicted inFIG. 43andFIG. 44may comprise different stent material(s)85. When the solid film66-A comprises different stent material(s)85than solid film66-B and solid film66-C, solid film66-B comprises different stent material(s)85than solid film66-A and solid film66-C and solid film66-C comprises different stent material(s)85than solid film66-A and solid film66-B, the layers51form within the roll thickness57, which have a layer thickness91-A, layer thickness91-B and layer thickness91-C.

AlthoughFIG. 44depicts solid film66-A, solid film66-B and solid film66-C being wrapped around the shaft74two times, the solid film66-A may be wrapped around the shaft74greater than or less than two times, solid film66-B may be wrapped around the shaft74greater than or less than two times and solid film66-C may be wrapped around the shaft74greater than or less than two times by increasing or decreasing the length68of the solid film66-A, the solid film66-B and/or the solid film66-C. Moreover, althoughFIG. 42depicts that solid film66-A, solid film66-B and solid film66-C are both are wrapped around the shaft74the same number of times, in other embodiments solid film66-A may be wrapped around the shaft74greater or lesser times than solid film66-B and/or solid film66-C, solid film66-B may be wrapped around the shaft74greater or lesser times than solid film66-A and/or solid film66-C and solid film66-C may be wrapped around the shaft74greater or lesser times that solid film66-A and/or solid film66-B.

It should be appreciated that it is possible for the position of solid film66-A, solid film66-B and solid film66-C to be positioned differently than what is shown inFIG. 43, wherein solid film66-A is positioned near the Beginning Of The Roll58, solid film66-B is positioned in the middle of the roll and solid film66-C is positioned near the End Of The Roll59of the solid films66arranged in series. For example, where the position of the solid film66within the series is formatted (near Beginning Of The Roll58, middle of the roll, near End Of The Roll59), each solid film66may have the position within the series depicted inFIG. 61in one of the following configurations: (F-A, F-C, F-B) or (F-B, F-A, F-C) or (F-B, F-C, F-A) or (F-C, F-B, F-A) or (F-C, F-A, F-B); wherein “F-A” refers to solid film66-A, “F-B” refers to solid film66-B and “F-C” refers to solid film66-C.

AlthoughFIG. 41andFIG. 42depict three solid film(s)66in series, in other embodiments there may be more than three solid film(s)66wrapped around the shaft74in series to form the roll52that is formed into the un-oriented tube42, which is converted into oriented tube38and/or the stent10. The maximum number of films66that may be incorporated into the roll52depends on the practical limit of the un-oriented tube wall thickness45and/or the number of wraps of the films66around the shaft74. When there are more than three solid films66incorporated into the roll52in series, each of the solid films66may comprise the same stent material(s)85or at least two of the film(s)66may comprise different stent material(s)85. In an embodiment, there may be between 2 to 1000 solid films66wrapped around the shaft74in series when forming the roll52. In other embodiments, there may be equal to or greater than 1000 solid films wrapped around the shaft74in series when forming the roll52.

FIG. 45depicts on embodiment of an Indirect Formation Process Including Active Ingredient(s)140from the side view. The Indirect Roll Formation Process Including Active Ingredients140forms the Roll Including Active Ingredient(s)143that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. As depicted inFIG. 45, the Roll Formation Process Including Active Ingredients140comprises the shaft74, the solid film66, the Film Rotation Direction139, the active ingredient(s)34, the Film Major surface73, an Active Ingredient Storage Area141and an Active Ingredient-Free Area142. In this example, the active ingredient(s)34are positioned at least partially on the major surfaces73of the solid film66within at least one Active Ingredient Storage Areas141. The active ingredient(s)34may be applied to either one or both major outer surface(s)73of the solid film(s)66by spraying, brushing or rolling the active ingredient(s)34onto at least one of the major surfaces73of the solid film66, wherein the active ingredient(s)34may be in a liquid, solid or solid and liquid form (a “mixture”). Alternatively, the active ingredient(s)34may be applied to the solid film66by chemical vapor deposition (e.g. electrostatic spray assisted vapor deposition, sherardizing, epitaxy), physical vapor deposition (cathodic arc deposition, electron beam physical vapor deposition, ion plating, ion beam assisted deposition, magnetron sputtering, pulsed laser deposition, sputter deposition, vacuum deposition, vacuum evaporation, evaporation deposition, pulsed electron deposition), and roll-to-roll coating processes (air knife coating, anilox coater, flexo coater, gap coating, gravure coating, immersion (dip coating), kiss coating, metering rod (Meyer bar) coating, reverse roll coating, forward roll coating, silk screen coater, rotary screen coater, extrusion coating, curtain coating, slide coating, slot die bead coating, tensioned-web slot die coating, inkjet printing, lithography, flexography). The active ingredient(s)34comprising solid particles or liquid droplets may include a charge that attracts the active ingredient(s)34or the vehicle carrying the active ingredient(s)34to the targeted Active Ingredient Storage Area141. For example, the active ingredient(s)34in the form of the particle or droplet154may include a positive charge that propels the active ingredient(s)34toward the grounded solid film66or a grounded object positioned directly behind Active Ingredient Storage Area141on part or the entire major surface of the solid film66in a way that results in the active ingredient(s)34being positioned within the Active Ingredient Storage Area141prior to forming the Roll Including Active Ingredient(s)143. The active ingredient(s)34may be un-dissolved, partially dissolved or completely dissolved in at least one solvent86when applied to part or the complete major outer surface(s)73of the solid film66in a way that when the solvent86is removed that the active ingredient(s)34are at least partially or completely adhered to or at least partially or completely imbedded in the solid film's66major outer surface(s)73within the Active Ingredient Storage Area(s)141. Alternatively, or additionally, the active ingredient(s)34may be mixed with at least one solvent86and at least one stent material85to form a solution83or mixture that may be sprayed onto at least one of the major surfaces73of the solid film66within the Active Ingredient Storage Area141and the solution83is allowed to partially or completely dry, which results in the active ingredient(s)34being adhered to at least one of the major surfaces73of the solid film(s)66.

Alternatively, or additionally, the active ingredient(s)34may be applied in a solid form. The solid particles of the active ingredient(s)34may be applied to the swollen film66, wherein the swollen film66comprises the solid film66wherein the solvent(s)86have not been completely removed from the solid film66. The particles comprising the active ingredient(s)34may be within the size range of greater than 0.000 to 0.010 mm, more narrowly between 0.000 to 0.005 mm. The swollen film66is softer than the completely solid film that contains 0 wt. % solvent(s)86to less than 0.5 wt. % solvent(s)86and if the solid particles of the active ingredient(s)34are, for example, sprayed or otherwise impacted on the outer major surface(s)73of the swollen film66, the solid particles comprising the active ingredient(s)34at least partially penetrate the solid film thickness67, which results in the solid active ingredient(s)34being adhered to the outer major surface(s)73of the solid film66or imbedded within the solid film66when the solvent(s)86are substantially completely removed from the solid film66. Alternatively, or additionally, the solid particles comprising the active ingredient(s)34may also be applied to the softened film66, wherein warming the solid film66produces the softened solid film66. If the solid particles comprising the active ingredient(s)34are, for example, sprayed on at least one of the outer major surface(s)73of the warm, softened film66or otherwise impacted on the warm, softened film66, the solid particles comprising the active ingredient(s)34at least partially penetrate the warm, softened solid film thickness67, which results in the solid active ingredient(s)34being adhered to or embedded within the outer major surface(s)73of the solid film66when the warmed, softened solid film66is cooled. The solid film66may be heated up to about the melting temperature of at least one or all of the stent material(s)85within the solid film66to soften the solid film66to enable at least partial or complete penetration of the applied solid particles comprising the active ingredient(s)34to adhere to the outer major surface(s)73of the solid film66or remain embedded within the solid film66when the solid film66is cooled to a temperature below the glass transition temperature of at least one of the stent material(s)85comprising the solid film66or cooling the warmed solid film66to a normal room temperature.

The active ingredient(s)34or the active ingredient(s)34and at least one stent material85may be positioned within the roll52, the un-oriented tube42, the oriented tube38and/or the stent10in at least one of the following locations: (1) between all the film thicknesses67(refer toFIG. 49), (2) between at least one part of the film thicknesses67and not between one part of the film thicknesses67(refer toFIG. 46), (3) within all the film thicknesses67(refer toFIG. 25), (4) within at least one part of the film thicknesses67and not within at least one other part of the film thicknesses67(refer toFIG. 62,FIG. 63,FIG. 64), (5) within all of the film thicknesses67and between all of the film thicknesses67(refer toFIG. 88,FIG. 89,FIG. 90), (6) within at least one part of the film thicknesses67and between at least one part of the film thicknesses67, (7) within all of the film thicknesses67and between at least one part of the film thicknesses67or (8) within at least one part of the film thicknesses67and between all of the film thicknesses67. In an embodiment, positioning the active ingredient(s)34within two Active Ingredient Storage Areas141produces the Roll Including Active Ingredient(s)143depicted inFIG. 46. The Roll Including Active Ingredient(s)143is produced by positioning the Beginning Of The Roll58in contact with the shaft outer surface78and wrapping the solid film66around the cylindrical-shaped shaft74in the film rotation direction139until the entire length68of the solid film66encircles the shaft74in a way that positions the active ingredient(s)34between the film thicknesses67of the wrapped solid film66as depicted inFIG. 45. Another method of producing the Roll Including Active Ingredient(s)143depicted inFIG. 46is to arrange the active ingredient(s)34on the solid film66as depicted inFIG. 47. The active ingredient(s)34may be included in any of the solid film66, the roll52, the coating30and the stent10configurations or combinations thereof depicted in the figures. Alternatively, at least one solid film66may not include the active ingredient(s)34(refer toFIG. 24).

In another embodiment of the Roll Including Active Ingredient(s)143there may be only one Active Ingredient Storage Area141near the Beginning Of The Roll58, which results in the active ingredient(s)34being positioned only near the inner surface62of the roll52(not depicted). Conversely, there may be only one Active Ingredient Storage Area141near the End of the Roll59, which results in the active ingredient(s)34being positioned only near the outer surface61of the roll61(not depicted). When there are active ingredient(s)34located near the inner surface48of the un-oriented tube42and the outer surface47of the un-oriented tube42, the active ingredient(s)34positioned near the inner surface48may be the same or different than those positioned near the outer surface47. For example, those positioned near the outer surface47may inhibit restenosis and those positioned near the inner surface48may promote endothelialization or inhibit thrombosis (e.g., antiplatelet), when the un-oriented tube42that is made from the Roll Including Active Ingredient(s)143is converted into the oriented tube38and/or the stent10. In one more embodiment, the Indirect Roll Formation Process Including Active Ingredient(s)140comprises the solid film66having one Active Ingredient Storage Area141and the remainder of the solid film66is an Active Ingredient-free Area142as depicted inFIG. 48, wherein the Active Ingredient-free Area142is 2 near the End Of The Roll59. The Indirect Roll Formation Process Including Active Ingredient(s)140depicted inFIG. 48produces the Roll Including Active Ingredient(s)143depicted inFIG. 49. Alternatively,FIG. 48may comprise one solid film66-A including the active ingredient(s)34and one solid film66-B excluding the active ingredient(s)34, wherein solid film66-A is wrapped first around the shaft74at least one time and the solid film66-B is wrapped second around the shaft74at least one time to form the Roll Including Active Ingredient(s)143, or the opposite.

Referring toFIG. 50, the Indirect Roll Formation Process Including Fast Degrading Rate Films146comprises at least one Fast Degrading Rate Film144and at least one Slow Or Medium Degrading Rate Film145. The Fast Degrading Rate Film144allows at least part or all of the active ingredient(s)34positioned near the Fast Degrading Rate Film144to be delivered by the stent10into the treatment site35. In embodiments, the Fast Degrading Rate Film144allows at least part or all of the active ingredient(s)34to be delivered by the stent10into the treatment site35within greater than 0 to 7 days, within greater than 0 to 14 days, within greater than 0 to 21 days, greater than 0 to 28 days, within greater than 0 to 35 days, within greater than 0 to 42 days, within greater than 0 to 56 days, within greater than 0 to 63 days after the stent10is deployed within the anatomical lumen36. The Slow Or Medium Degrading Rate Film145provides mechanical support to the stent10until the anatomical lumen36is self-supporting. In an embodiment, the Fast Degrading Rate Film144is depicted inFIG. 50andFIG. 51as a dashed line and the Slow Or Medium Degrading Rate Film145is depicted as a solid line for ease of illustration. The Fast Degrading Rate Film144may be positioned near the Beginning of the Roll58and/or the End of the Roll59and the Slow Or Medium Degrading Rate Film145may be positioned between the two Fast Degrading Rate Films144. The Fast Degrading Rate Film144and the Slow Or Medium Degrading Rate Film may be connected with the optional abutting or overlapping splice147as depicted inFIG. 50. The Roll Including Active Ingredients(s)143is formed using The Roll Formation Process Including Fast Degrading Rate Film146by placing the Beginning Of The Roll58in contact with the shaft outer surface78and wrapping the interconnected solid films66around the shaft74in the film rotation direction139until the entire lengths68of the spliced solid films66encircle the shaft74as depicted inFIG. 50. Alternatively, the three separate solid films66may be individually wrapped around the shaft74by: (1) wrapping the first Fast Degrading Rate Film144including the active ingredient(s)34around the shaft74at least one time with the active ingredient(s)34facing away from the shaft74; (2) wrapping the only Slow Or Medium Degrading Rate Film145including active ingredient(s)34around the shaft74at least one time with the active ingredient(s)34facing toward the shaft74on top of the previously wrapped Fast Degrading Rate Film144including the active ingredient(s)34; and (3) wrapping the second Fast Degrading Rate Film114including the active ingredient(s)34around the shaft74at least one time with the active ingredient(s)34facing toward the shaft74on top of the previously wrapped Slow Or Medium Degrading Rate Film144including the active ingredient(s)34. In yet more embodiment, as depicted inFIG. 51, the three separate solid films66may be individually wrapped around the shaft74by: (1) wrapping the first Fast Degrading Rate Film144excluding the active ingredient(s)34around the shaft74; (2) wrapping the only Slow Or Medium Degrading Film145including active ingredient(s)34located in the three Active Ingredient Storage Areas141around the shaft74with the active ingredient(s)34facing toward the shaft74on top of the previously wrapped Fast Degrading Rate Film144excluding the active ingredient(s)34; and (3) wrapping the second Fast Degrading Rate Film114excluding the active ingredient(s)34around the shaft74at least one time on top of the previously wrapped Slow or Medium Degrading Rate Film144including the active ingredient(s)34. The methods depicted inFIG. 50andFIG. 51result in producing the Roll Including Active Ingredient(s)143depicted inFIG. 52. As depicted inFIG. 52, in an embodiment the Fast Degrading Rate Film144, which is shown as a dashed line for ease of visualization, may be facing the anatomical lumen36near the outer surface66and near the contents6near the inner surface61, when the Roll Including Active Ingredient(s)143is formed into the un-oriented tube43, which is converted into oriented tube38and/or the stent10. Additionally, the interior portion of the stent10wall thickness13may also include the active ingredient(s)34so that drug delivery occurs during at least part or the complete time that it takes for the Slow Or Medium Degrading Rate Film144to be resorbed.

FIG. 52depicts an embodiment of the Roll Including Active Ingredient(s)143, wherein the Fast Degrading Rate Film144located near the roll inner surface62comprises one wrap of the Fast Degrading Rate Film144, the Slow Or Medium Degrading Rate Film144located in the middle of the roll thickness57comprises three wraps of the Slow Or Medium Degrading Rate Film145and the other Fast Degrading Rate Film144located near the roll outer surface61comprises one wrap of the Fast Degrading Rate Film144. Additionally,FIG. 52depicts that the Roll Including Active Ingredient(s)143includes: (1) one layer of the active ingredient(s)34positioned near the roll outer surface61that is positioned between one Fast Degrading Rate Film144thickness67(facing abluminal surface) and one Slow Degrading Rate Film145thickness67(facing luminal surface); (2) one layer the active ingredient(s)34that is positioned between two Slow Degrading Rate Film144thicknesses67(facing abluminal surface) and two Slow Degrading Rate Film144thicknesses67(facing luminal surface); and (3) one layer of the active ingredient(s)34positioned near the roll inner surface62that is positioned between one Fast Degrading Rate Film144thickness67(facing luminal surface) and one Slow Degrading Rate Film145thickness67(facing abluminal surface). It should be appreciated that there may be greater than or less than three layers of the active ingredient(s)34within the Roll Including Active Ingredient(s)143; there may be greater than or less than two wraps of the Fast Degrading Rate Film144within the Roll Including Active Ingredients143and there may be greater than or less than three wraps of the Slow Or Medium Degrading Rate Film145within the Roll Including Active Ingredient(s)143.

As depicted inFIG. 53, in an embodiment of the Indirect Roll Formation Process Including Multiple Films148, the active ingredient(s)34are positioned between at least two of the solid films'66major surfaces73within at least one of the active ingredient Storage Area(s)141. The Roll Including Active Ingredient(s)143is made by positioning the Beginning Of The Roll58in contact with the shaft outer surface78and wrapping the multiple solid films66around the shaft74in the film rotation direction139until the entire length68of the multiple solid films66encircle the shaft74. The Indirect Roll Formation Process Including Multiple Films148depicted inFIG. 53produces the Roll Including Active Ingredient(s)143as depicted inFIG. 54that is formed into the un-oriented tube38, which is converted into the oriented tube38and/or the stent10. Alternatively, as depicted inFIG. 55, in another embodiment of the Indirect Roll Formation Process Including Multiple Films148, there are three solid films66comprising the Indirect Roll Formation Process Including Multiple Films148.FIG. 55depicts the solid film66-A as a dashed line on the bottom, the solid film66-B in the middle as a solid line and solid film66-C on the top as a solid line. There is a layer of the active ingredient(s)34located between the solid film66-A and the solid film66-B and an Active Ingredient-Free Area142located between solid film66-B and solid film66-C inFIG. 55. The Active Ingredient-Free Area142has no active ingredient(s)34located between the two solid films66. In another embodiment, the active ingredient(s)34may be located between solid film66-B and solid film66-C and the Active Ingredient-Free Area142may be positioned between solid film66-A and solid film66-B. In yet one more embodiment, the active ingredient(s)34may be positioned between solid film66-A and solid film66-B and the active ingredient(s) may be positioned between solid film66-B and solid film66-C. The three superimposed solid films66including the active ingredient(s)34are wrapped around the shaft74to form the Roll Including Active Ingredient(s)143depicted inFIG. 56. AlthoughFIG. 55depicts three solid films66comprising the roll52, one layer of the active ingredient(s)34between two of the solid films66and one Active Ingredient-Free Area142, in other embodiments there may be greater than three solid films66, greater than one layer of the active ingredient(s)34between greater than two of the solid films66and greater than one Active Ingredient-Free Area142within the Roll Including Active Ingredients143. The solid film66-A, the solid film66-B and the solid film66-C may comprise the same stent material(s)85or at least one or all or the solid films66may comprise different stent material(s)85. The film thickness67within solid film66-A, the film thickness67within solid film66-B or the film thickness67within solid film66-C may be the same or at least one or all the solid films66may comprise different thicknesses67.

As depicted inFIG. 57, in an embodiment the Indirect Roll Formation Process Including Active Ingredient(s)140may comprise the shaft74, three different solid films66positioned in series and active ingredient(s)34positioned on at least part or all of the film major surface73of the middle solid film66-B.FIG. 57depicts the solid film66-A positioned near the Beginning Of The Roll58, the solid film66-C positioned near the End Of The Roll59and the solid film66-B positioned between the solid film66-A and the solid film66-B. The Indirect Roll Formation Process Including Active Ingredient(s)140depicted inFIG. 57produces the Roll Including Active Ingredient(s)143depicted inFIG. 58that is formed into the unoriented tube42, which is converted into the oriented tube38and/or the stent10. The Roll Including Active Ingredient(s)143depicted inFIG. 58is formed by wrapping the solid film66-A around the shaft74first, wrapping the solid film66-B including the active ingredient(s)34around the shaft74second and wrapping the solid film66-C around the shaft74third. As depicted inFIG. 58, the Indirect Roll Formation Process Including Active Ingredient(s)140results in the Roll Including Active Ingredient(s)143comprising two Active Ingredient-Free Areas142located near the inner surface of the roll62, one Active Ingredient Storage Area141located near the middle of the roll thickness57and two Active Ingredient-Free Areas142located near the outer surface of the roll61. In other embodiments, there may be greater than or less than two Active Ingredient-Free Zones142located near the roll inner surface62and/or roll outer surface61and greater than or less than one Active Ingredient Storage Areas141located near the middle of the roll thickness57.

As depicted inFIG. 59, in an embodiment the Indirect Roll Formation Process Including Multiple Films148may comprise the shaft74, two partially superimposed solid films66and active ingredient(s)34, wherein the first solid film66-A is longer than the second solid film66-B and the active ingredient(s)34are located between the solid film66-A and the solid film66-B. The Indirect Roll Formation Process Including Multiple Films148depicted inFIG. 59produces the Roll Including Active Ingredient(s)143depicted inFIG. 60that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. Positioning the solid film66-A against the shaft74and wrapping solid film66-A and the solid film66-B that includes the active ingredient(s) around the shaft74until the entire length69of the solid film66-A encircles the shaft74produces the Roll Including Active Ingredient (s)143depicted inFIG. 60. Alternatively, or additionally, the active ingredient(s)34may be positioned within the solid film66-B, which results in forming the Roll Including Active Ingredients143depicted inFIG. 61that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. AlthoughFIG. 60andFIG. 61depict wrapping the solid film66-A around the shaft74one time prior to wrapping the solid film66-B around the shaft74and wrapping the solid film66-B around the shaft74one time after wrapping the solid film66-A around the shaft74and wrapping the solid film66-A around the shaft74one additional time after wrapping the solid film66-B around the shaft74, in other embodiments the solid film66-A may be wrapped around the shaft74greater than one time prior to wrapping the solid film66-B around the shaft74, the solid film66-B may be wrapped around the shaft74greater than one time and the solid film66-A may be wrapped around the shaft74greater than one time after wrapping the solid film66-B around the shaft74. Additionally, even thoughFIG. 60andFIG. 61show that the solid film66-A is wrapped around the shaft74the same number of times prior to wrapping the solid film66-B around the shaft74as after wrapping the solid film66-B around the shaft74, in other embodiments the solid film66-A may be wrapped around the shaft74additional times prior to wrapping the solid film66-B around the shaft74than after wrapping the solid film66-B around the shaft74, or the opposite. Furthermore, in other embodiments, the solid film66-B may be wrapped around the shaft74greater than one time when forming the Roll Including active ingredient143. The length68of the solid film66-B may cover between 0.2% to 98% of the length68of the solid film66-A. In other embodiments, the length of solid film66-B may cover equal to or less than 0.2% of the length of the solid film66-A or equal to or greater than 98% of the length of the solid film66-A. Although the Roll Formation Process Including Multiple Films148depicted inFIG. 59shows that the active ingredient(s)34are positioned so that the Roll Including Active Ingredient(s)143will have the active ingredient(s)34positioned around about one circumference of the roll52, in other embodiments the active ingredient(s)34may be positioned around greater than or less than one circumference of the roll52. While the Roll Including Active Ingredient(s)143depicted inFIG. 60andFIG. 61show that the active ingredient(s)34are positioned approximately in the middle of the roll thickness57, in other embodiments the active ingredient(s)34may be located: (1) near the roll inner surface62, (2) the roll outer surface61, (3) the middle of the roll thickness57and the roll inner surface62, (4) the middle of the roll thickness57and the roll outer surface61, (5) the roll inner surface62and the roll outer surface61or (6) the roll inner surface61and the middle of the roll57and the roll outer surface62.

The Rolls Including Active Ingredient(s)143depicted inFIG. 60andFIG. 61may be adapted by superimposing at least one additional solid film66in the Indirect Roll Formation Process Including Multiple Films148depicted inFIG. 59. For example, the additional solid film66-C, solid film66-D, solid film66-E and so on may be incorporated into the Indirect Roll Formation Process Including Multiple Films148. The additional solid film(s)66may be partially or completely superimposed on and/or under the solid film66-A and/or solid film66-B to form a multilayer unoriented tube42including active ingredient(s)34instead of a bilayer un-oriented tube42including active ingredient(s)34. In an embodiment the additional active ingredient(s)34may be located: (1) between at least one of the additional solid film(s)66and the solid film66-A and/or solid film66-B, (2) between at least two additional solid film(s), (3) within at least one of the additional solid film(s)66, (4) between at least one of the additional solid film(s)66and the solid film66-A or solid film66-B and within at least one of the additional solid film(s)66and/or (5) between at least two additional solid film(s)66and within at least one of the additional solid film(s)66. The solid film66-A, solid film66-B and the additional solid film(s)66depicted inFIG. 59,FIG. 60andFIG. 61may be comprised of the same stent material(s)85. Alternatively, at least one or all the solid film66-A, solid film66-B and the additional solid film(s)66depicted inFIG. 59,FIG. 60andFIG. 61may be comprised of different stent material(s)85. The solid film66-A, solid film66-B and the additional solid film(s)66depicted inFIG. 59,FIG. 60andFIG. 61may have the same film thickness67. Alternatively, at least one or all the solid film66-A, solid film66-B and the additional solid film(s)66depicted inFIG. 59,FIG. 60andFIG. 61may have different film thicknesses67.

Notwithstanding that the Rolls Including Active Ingredient(s)143depicted inFIG. 46,FIG. 49,FIG. 52,FIG. 54,FIG. 56,FIG. 58andFIG. 60and the variants thereof depict the active ingredient(s)34positioned between at least two film thicknesses67, in other embodiments the active ingredient(s)34may be positioned within at least one or all the solid film(s)66or all the film thicknesses67.FIG. 62throughFIG. 67depict examples of the Roll Formation Process Including Active Ingredient(s)140, wherein the active ingredient(s)34are at least partially or completely positioned within the film thickness67prior to forming the Roll Including Active Ingredient(s)143. The active ingredient(s)34may be incorporated into the solid film thickness67by mixing the active ingredient(s)34in the solution83used to form the liquid film87and the solid film66depicted inFIG. 23. In an embodiment the active ingredient(s)34are completely dissolved in the solution83so that the dissolved active ingredient(s)34are substantially evenly dispersed within the stent material(s)85comprising the solid film66. In another embodiment the active ingredient(s)34completely un-dissolved in the solution83so that the solid particles comprising the active ingredient(s)34are randomly or uniformly dispersed within the stent material(s)85comprising the solid film66. In another embodiment the active ingredient(s)34are partially dissolved within the solution83so that the randomly or uniformly dispersed solid active ingredient(s)34particles are separated by a relative uniform mixture of the dissolved active ingredient(s)34and the stent material(s)85. ThoughFIG. 62throughFIG. 67depict the active ingredient(s)34in circular shape, in other embodiments the active ingredient(s)34may be other shapes. Moreover, even though the figures depict the active ingredient(s)34having the same size, in other embodiment(s)34the size of the active ingredient(s)34within the solid film34may vary from particle to particle. The number of sizes of the particles comprising the active ingredient(s)34is virtually unlimited within the boundary specifications provided herein. It should be appreciated that although the figures show the active ingredient(s)34protruding from the film major surfaces73, that in other embodiments the active ingredient(s)34are completely encapsulated within the solid film(s)66or that at least part of the active ingredient(s)34protrude outside the film major surface(s)73and at least part of the active ingredient(s)34are encapsulated within the solid film66.

FIG. 62depicts and embodiment of the Indirect Roll Formation Process Including Active Ingredient(s)140, wherein the active ingredient(s)34are located at least partially or completely within the solid film66near the Beginning Of The Roll58, which results in the active ingredient(s)34being positioned near the inner surface48of the un-oriented tube42that is converted into the oriented tube38and/or the stent10. Alternatively, in another embodiment the active ingredient(s)34may be located at least partially or completely within the film thickness67near the End Of The Roll59, which results in the active ingredient(s)34being positioned near the outer surface47of the un-oriented tube42(not depicted). The Indirect Roll Formation Process Including Active Ingredient(s)140depicted inFIG. 62may comprise two separate or connected solid films66. The Roll Including Active Ingredients143may be produced by wrapping the solid film66-A, which includes the active ingredient(s)34, around the shaft74first and then wrapping the solid film66-B, which excludes the active ingredient(s)34around the shaft74second, or the opposite. The solid film66-A and/or the solid film66-B may be wrapped around the shaft74once or multiple times. In an embodiment, the solid film66-A may be wrapped around the shaft74the same number of times as solid film66-B. In other embodiments, the solid film66-A is wrapped around the shaft74more times than solid film66-B or the solid film66-B is wrapped around the shaft74more times than solid film66-A. In yet one more embodiment, the active ingredient(s)34may be incorporated into solid film66-A and solid film66-B, so that every wrap around the shaft74comprises a solid film66comprising a mixture of the active ingredient(s)34and the stent material(s)85. The solid film66-A and the solid film66-B may comprise the same stent material(s)85. In other embodiments, the solid film66-A and solid film66-B may comprise different stent material(s)85. The solid film66-A and the solid film66-B may comprise the same film thickness67. In other embodiments, the solid film66-A and solid film66-B may comprise different film thicknesses67. For example, solid film66-A may be thicker than solid film66-B or the opposite.

FIG. 63depicts an embodiment of the Indirect Roll Formation Process140, wherein the active ingredient(s)34are located within the solid film66near the Beginning Of The Roll58, the End Of The Roll59and in the middle, which results in the active ingredient(s)34being positioned near the inner surface48of the un-oriented tube42, outer surface47of the un-oriented tube42and in the middle of the un-oriented tube wall thickness45. The Indirect Roll Formation Process Including Active Ingredient(s)140depicted inFIG. 63comprises five separate or connected solid films66. The Roll Including Active Ingredients143that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10, may be produced by wrapping the solid film66-A, which includes the active ingredient(s)34, around the shaft74first, then wrapping the solid film66-B, which excludes the active ingredient(s)34around the shaft74second, wrapping the solid film66-C, which includes the active ingredient(s)34, around the shaft74third, wrapping the solid film66-D, which excludes the active ingredient(s)34around the shaft74fourth and wrapping the solid film66-E, which includes the active ingredient(s)34around the shaft74fifth. The solid film66-A, solid film66-B, solid film66-C, solid film66-D and solid film66-E may be wrapped around the shaft74once or multiple times. The solid film66-A, solid film66-B, solid film66-C, solid film66-D and solid film66-E may be wrapped around the shaft74the same number of times or at least one or all the solid films66may be wrapped around the shaft74a different number of times. For example, the solid film66-B and solid film66-D may be wrapped around the shaft74more times than solid film66-A, solid film66-C and solid film66-E, or the opposite. It is possible that solid film66-E be wrapped around the shaft74more than solid film66-C and solid film66-C be wrapped around the shaft74more that solid film66-A so that the dosage active ingredient(s)34-E is greater than the dosage of active ingredient(s)34-C and the dosage of active ingredient(s)34-C is greater than the dosage of active ingredient(s)34-A, or the opposite. It is also possible that the solid film66-C is wrapped around the shaft74more times than solid film66-E and/or solid film66-A so that the dosage of active ingredient(s)34-C is greater than the dosage of active ingredient(s)34-E and/or active ingredient(s)34-A. Alternatively, or additionally, the quantity (or “dosage”) of the active ingredient(s)34in each wrap of the solid film66may be the same or different within each wrap or within each Active Ingredient Storage Area141. For example, the dosage of active ingredient(s)34-A, active ingredient(s)34-C and active ingredient(s)34-E may be the same or different, wherein: (1) the dosage of active ingredient(s)34-A is greater than active ingredient(s)34-C and the dosage of active ingredient(s)34-C is greater than active ingredient(s)34-E; (2) the dosage of active ingredient(s)34-E is greater than active ingredient(s)34-C and the dosage of active ingredient(s)34-C is greater than active ingredient(s)34-A; (3) the dosage of active ingredient(s)34-A is greater than active ingredient(s)34-E and the dosage of active ingredient(s)34-A is greater than active ingredient(s)34-C; (4) the dosage of active ingredient(s)34-E is greater than active ingredient(s)34-A and the dosage of active ingredient(s)34-A is greater than active ingredient(s)34-C; (5) the dosage of active ingredient(s)34-C is greater than active ingredient(s)34-A and the dosage of active ingredient(s)34-A is greater than active ingredient(s)34-E; and (6) the dosage of active ingredient(s)34-C is greater than active ingredient(s)34-E and the dosage of active ingredient(s)34-E is greater than active ingredient(s)34-A. The solid film66-A, solid film66-B, solid film66-C, solid film66-D and solid film66-E may comprise the same stent material(s)85or at least one of the solid films66may comprise different stent material(s)85. The solid film66-A, solid film66-B, solid film66-C, solid film66-D and solid film66-E may comprise the same film thickness67or at least one or all the solid films66may comprise a different film thickness67. The solid film66-A, solid film66-B, solid film66-C, solid film66-D and solid film66-E may comprise the same film length68or at least one of the solid films66may comprise a different film length68. The Film Formation Process Including Active Ingredient(s)140depicted inFIG. 63may be adapted so that there are greater than three Active Ingredient Storage Areas141and two Active Ingredient-Free Areas142. For example, two active ingredient-Free Areas142may be added to the Indirect Roll Formation Process138depicted inFIG. 63so that there is one active ingredient-Free Area142located near the Beginning Of The Roll58and one active ingredient-Free Area142located near the End of the Roll59so that the first and last wrap of the solid film(s)66around the shaft74do not include the active ingredient(s)34. In yet one more example, there may be four or more active ingredient Storage Areas141and three or more active ingredient-Free Areas142incorporated into the Roll Formation Process138depicted inFIG. 63so that the pattern of two active ingredient Storage Areas141separated by one active ingredient-Free Area142is repeated within the roll thickness57until the desired un-oriented tube42wall thickness45is achieved.

FIG. 64depicts one more embodiment of Indirect Roll Formation Process Including Active Ingredient(s)140, wherein the active ingredient(s)34are located within the film thickness67and the Active Ingredient Storage Area141is located in the middle of the roll thickness57of the film length68. The Indirect Roll Formation Process Including Active Ingredient(s)140depicted inFIG. 64comprises three solid films: (1) solid film66-A, which is positioned near the Beginning of the Roll58; (2) solid film66-B, which is positioned near the End of the Roll59and (3) solid film66-C, which is positioned between solid film66-A and solid film66-B. First wrapping solid film66-A around the shaft74, then wrapping solid film66C around the shaft74and finally wrapping solid film66-B around the shaft74forms the Roll Including Active Ingredients143that is formed into the un-oriented tube74, which is converted into the oriented tube38and/or the stent10. The solid film66-A may be connected or disconnected to solid film66-C and the solid film66-C may connected to the solid film66-B prior to forming the Roll Including Active Ingredients143. Solid film66-A, solid film66-B and solid film66-C may comprise the same stent material(s)85. Alternatively, the at least one of the solid films66-A,66-B or66-C may comprise at least one different stent material85than at least one of the other solid films66. The length68of the solid film66-A, the solid film66-B and the solid film66-C may be the same or at least one or all the solid films66may have a different length68. For example, solid film66-A may be greater in length68than solid film66-B and solid film66-B may be greater in length68than solid film66-C; solid film66-B may be greater in length68than solid film66-C and solid film66-C may be greater in length68than solid film66-A; solid film66-C may be greater in length68than solid film66-A and solid film66-A may be greater in length68than solid film66-B; solid film66-B may be greater in length68than solid film66-A and solid film66-A may be greater in length68than solid film66-C; solid film66-B and solid film66-A may be greater in length68than solid film66-C; solid film66-C may be greater in length68that solid film66-A and solid film B and solid film66-A; solid film66-A may be greater in length68than solid film66-B and solid film66-C; and solid film66-B may be greater in length68than solid film66-A and solid film66-C. Notwithstanding thatFIG. 64depicts that solid film66-A, solid film66-C and solid film66-B have the same film thickness67, in other embodiments at least one of the solid films66may have a different film thickness67than at least one of the other solid films66.

FIG. 65depicts one more embodiment of the Indirect Roll Formation Process Including Multiple Films148, wherein there is one solid film66-A superimposed on another solid film66-B, wherein the solid film66-B has the active ingredient(s)34located within the film thickness67and solid film66-A does not include any active ingredient(s)34. Wrapping the two superimposed solid films66around the shaft74forms the Roll Including Active Ingredient(s)143that is formed into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10. Although,FIG. 65depicts the solid film66-B including the active ingredient(s)34within the film thickness67and sold film66-A excluding the active ingredient(s) within the film thickness67, in other embodiments the solid film66-A may include the active ingredient(s)34within the film thickness67and the solid film66-B may exclude the active ingredient(s)34, both solid film66-A and solid film66-B may exclude the active ingredient(s)34within the film thicknesses67or both solid film66-A and solid film66-B may include the active ingredient(s)34within the film thicknesses67. The solid film66-A and solid film66-B depicted inFIG. 65may comprise the same stent material(s)85. Alternatively, the solid film66-A depicted inFIG. 65may comprise different stent material(s)85than solid film66-B depicted inFIG. 65. In an embodiment the solid film66-A and solid film66-B depicted inFIG. 65may comprise the same film thicknesses67. Alternatively, the solid film66-A depicted inFIG. 65may be thicker than the solid film66-B depicted inFIG. 65, or the opposite.

The Indirect Roll Formation Process Including Multiple Films148depicted inFIG. 65may be adapted by superimposing at least one additional solid film66-C on solid film66-B prior to wrapping the solid films66around the shaft74as depicted inFIG. 66. The Indirect Roll Formation Process Including Multiple Films148may be adapted even further by including the active ingredient(s)34within the solid film66-A and/or the solid film66-C. In addition to the configuration depicted inFIG. 66, the Indirect Roll Formation Process Including Multiple Films148may be configured so that the active ingredient(s)34are located in one of the following configurations: (1) the solid film66-A includes the active ingredient(s)34and the solid film66-B and the solid film66-C do not include the active ingredient(s)34; (2) the solid film66-C includes the active ingredient(s)34and the solid film66-A and the solid film66-B do not include the active ingredient(s)34; (3) the solid film66-A and the solid film66-B include the active ingredient(s)34and the solid film66-C does not include the active ingredient(s)34; (4) the solid film66-A and the solid film66-C include the active ingredient(s)34and the solid film66-B does not include the active ingredient(s)34; and (4) the solid film66-B and the solid film66-C include the active ingredient(s)34and the solid film66-A does not include the active ingredient(s)34. As depicted inFIG. 66, there may be an Active Ingredient-Free Area142between the solid film66-A and the solid film66-C and between the solid film66-C and the solid film66-B. In other embodiments, there may be at least one Active Ingredient Storage Area141(not depicted) located between the solid film66-A and the solid film66-C and/or between the solid film66-C and the solid film66-B. The solid film66-A, the solid film66-B and the solid film66-C depicted inFIG. 66may be comprised of the same stent material(s)85. In other embodiments of the Roll Formation Process Including Multiple Films148, the solid film66-A comprises different stent material(s)85than the solid film66-B and the solid film66-C; the solid film66-B comprises different stent material(s)85than the solid film66-A and the solid film66-C or the solid film66-C comprises different stent material(s)85than the solid film66-A and the solid film66-C. Additionally, in yet more embodiments the Roll Formation Process Including Multiple Films148may comprise at least one of the following configurations: (1) the solid film66-A and solid film66-B may comprise the same stent material(s)85and solid film66-C may comprise different stent material(s)85; (2) the solid film66-A and solid film66-C may comprise the same stent material(s)85and solid film66-B may comprise different stent material(s)85; (3) the solid film66-B and solid film66-C may comprise the same stent material(s)85and solid film66-A may comprise different stent material(s)85; and (4) the solid film66-C and solid film66-A may comprise the same stent material(s)85and solid film66-B may comprise different stent material(s)85. The solid film66-A, the solid film66-B and the solid film66-C depicted inFIG. 66may have the same thickness67. In other embodiments, the solid film66-A may have a different thickness67than solid film66-B and solid film66-C; the solid film66-B may have a different thickness67than the solid film66-A and the solid film66-C and the solid film66-C may have a different thickness67than solid film66-A and solid film66-C. Additionally, in yet more embodiments, the Roll Formation Process138may have at least one of the following configurations: (1) the solid film66-A and solid film66-B may have the same thickness67and the solid film66-C may have a different thickness67; (2) the solid film66-A and the solid film66-C may have the same thickness67and solid film66-B may have a different thickness67; (3) the solid film66-B and solid film66-C may have the same thickness67and solid film66-A may have a different thickness67; and (4) the solid film66-C and the solid film66-A may have the same thickness67and the solid film66-B may have a different thickness67. AlthoughFIG. 66depicts three solid films66within the Indirect Roll Formation Process Including Multiple Films148, in other embodiments, there may be greater than three solid films66. Therefore, the Roll Formation Process138depicted inFIG. 38may be adapted to include solid film66-A, solid film66-B, solid film66-C, solid film66-D, solid film66-E, solid film66-F and so on, wherein at least one solid film66includes the active ingredient(s)34within the film thickness67. It should be appreciated that wrapping the superimposed films66around the shaft74creates a repeating pattern in the roll thickness57, wherein the pattern is the configuration depicted inFIG. 66comprising film66-A thickness67, film66-C thickness67and film66-B thickness67.

FIG. 67depicts one more embodiment of the Indirect Roll Formation Process Including Multiple Films148, wherein there is one longer, solid film66-A superimposed on another shorter solid film66-B and the solid film66-B has the active ingredient(s)34located within the film thickness67and solid film66-A does not include any active ingredient(s)34. The Roll Formation Process Including Multiple Films148depicted inFIG. 67forms the Roll Including Active Ingredients(s)143by wrapping the two solid films66around the shaft74. The resultant Roll Including Active Ingredient(s)143is configured so that the active ingredient(s)34are positioned within the middle of the thickness57of the roll53. In other embodiments, the film66-A includes the active ingredient(s)34and the film66-B excludes the active ingredient(s)34. In still other embodiments, both solid film66-A and solid film66-B include active ingredient(s)34within the film thicknesses67or both solid film66-A and solid film66-B exclude the active ingredient(s)34within the film thicknesses67. The solid film66-A and solid film66-B depicted inFIG. 67may comprise the same stent material(s)85. Alternatively, the solid film66-A depicted inFIG. 67may comprise different stent material(s)85than solid film66-B depicted inFIG. 67. In an embodiment the solid film66-A and solid film66B depicted inFIG. 67may comprise the same film thicknesses67. Alternatively, the solid film66-A depicted inFIG. 67may be thicker than the solid film66-B depicted inFIG. 67, or the opposite.

Although it is not depicted in the figures, there is another embodiment wherein the active ingredient(s)34are positioned between at least two or all the film thicknesses67and within at least one or all the film thicknesses67. Positioning the active ingredient(s)34between the film thicknesses67and within the film thicknesses67enables greater control over the release of the active ingredient(s)34during the duration of the treatment. For example, as each film thickness67or each layer51erodes additional active ingredient(s)34may be released into the treatment site35surrounding the implanted stent10in a layer-by-layer or film thickness-by-film thickness sequence. In an embodiment, at least one or all the active ingredient(s)34stored within the film thicknesses67may be more amorphous and at least one or all the active ingredient(s)34stored between the film thicknesses67may be more crystalline, which provides two different mechanisms of drug delivery: (1) the more soluble lower crystallinity active ingredient(s)34have a faster therapeutic effect but have a tendency to be washed away from the treatment site35thereby providing short term therapy and (2) the less soluble higher crystallinity active ingredient(s)34have a slower therapeutic effect but have a tendency to be retained within the treatment site35thereby providing longer term therapy. The two drug delivery mechanisms provide a controlled release of the active ingredient(s)34for a time that the mass of the stent10remains within the anatomical lumen36. In other embodiments, at least one or all the less amorphous active ingredient(s)34(are stored between at least two of the film thicknesses67and at least one or all the more crystalline active ingredient(s)34are stored within at least one of the film thicknesses67. In still other embodiments, at least one or all the less amorphous active ingredient(s)34are stored between at least two of the film thicknesses67and within at least one of the film thicknesses67or at least one or all the more crystalline active ingredient(s)34are stored within at least one of the film thicknesses67and between at least two of the film thicknesses67.

In an embodiment, at least one or all the active ingredient(s)34stored within the film thicknesses67may have a lower weight average molecular weight and at least one or all the active ingredient(s)34stored between the film thicknesses67may have a higher weight average molecular weight which provides two different mechanisms of drug delivery: (1) the more soluble lower weight average molecular weight active ingredient(s)34have a faster therapeutic effect (2) the less soluble higher weight average molecular weight active ingredient(s)34have a slower therapeutic. The two drug delivery mechanisms provide a controlled release of the active ingredient(s)34. In other embodiments, at least one or all the lower weight average molecular weight active ingredient(s)34are stored between at least two of the film thicknesses67and at least one or all the higher weight average molecular weight active ingredient(s)34are stored within at least one of the film thicknesses67. In still other embodiments, at least one or all the lower weight average molecular weight active ingredient(s)34are stored between at least two of the film thicknesses67and within at least one of the film thicknesses67or at least one or all the higher weight average molecular weight active ingredient(s)34are stored within at least one of the film thicknesses67and between at least two of the film thicknesses67.

In an embodiment, the low weight average molecular weight active ingredient(s)34(molecular weight between greater than 0 to 600,000 g/mol) may have a low crystallinity or a high crystallinity. In an embodiment, the high weight average molecular weight active ingredient(s)34(molecular weight between 600,000 to 2,000,000 g/mol) may have a low crystallinity or a high crystallinity.

FIG. 68depicts a Heated Tube Former256. The Heated Tube Former256minimally includes a pinch roller257and the shaft74.FIG. 68depicts a method of producing the un-oriented tube42, wherein at least one solid, film66is fed between the cylindrical-shaped shaft74and the cylindrical-shaped pinch roller257. The solid film(s)66being fed into the Heated Tube Former256may include the active ingredient(s)34positioned within the solid film(s)66and/or on at least one of the major surface(s)73of the solid film(s)66before the solid film(s)66enter the pinch point258. The shaft outer surface78and pinch roller outer surface261are maintained at a separation distance, or pinch point258, that compresses the film thicknesses67against the shaft outer surface78and/or the previously wrapped film thicknesses67that surround the shaft outer surface78when the film(s)66pass between the shaft74and the pinch roller257. The pinch roller257and/or the shaft74may be attached to a spring loaded mount (not depicted) or other mechanism that allows the gap between the pinch roller257and the shaft74to adjust in size so that the pinch roller257accommodates the larger un-oriented tube42thickness45as additional film thicknesses67are added to the un-oriented tube42wall thickness45or a mechanism that keeps a substantially constant pressure on the compressed film thicknesses67as they are passing through the pinch point258during formation of the un-oriented tube42. The shaft74spins in the clockwise direction259and the pinch roll257spins in the counterclockwise direction260, or the opposite, so that the film(s)66wrap around the shaft74during un-oriented tube42formation. To interconnect the film thicknesses67, the outer surface261of the pinch roller257and/or the outer surface78of the shaft74are maintained at a temperature between 0 and about 250.degree. C. In other embodiments the temperature of the outer surface260of the pinch roller257and/or the outer surface78of the shaft74are maintained at a temperature selected from the group of: (1) between 0 and 240.degree. C, (2) between 0 and 230.degree. C, (3) between 0 and 220.degree. C, (4) between 0 and 210.degree. C; (5) between 0 and 200.degree. C, (6) between 0 and 190.degree. C, (7) between 0 and 180.degree. C, (8) between 0 and 170.degree. C, (9) between 0 and 160.degree. C, (10) between 0 and 150.degree. C, (11) between 0 and 140.degree. C, (12) between 0 and 130.degree. C, (13) between 0 and 120.degree. C, (14) between 0 and 110.degree. C, (15) between 0 and 100.degree. C, (16) between 0 and 90.degree. C., (17) between 0 and 80.degree. C or (18) between 0 and 70.degree. C. When the Over-Film Thickness93passes over the Under-Film Thickness94that is supported by the shaft74in a cylindrical configuration, the heated pinch roller257presses the film thicknesses67together and quickly thermally fuses the Over-Film Thickness93to the Under-Film Thickness94by imparting heat on the film thicknesses67for the short duration that the film thicknesses67are compressed between the pinch roller257and the shaft74, which interconnects the film thicknesses67when the compressed film thicknesses67leave the pinch point258and cool. The heated Over-Film Thickness93and Under-Film Thickness94may be cooled when they pass through the gaseous environment90as the shaft74rotates the joined surfaces away from the pinch point258. The cooling process may be accelerated by blowing at least one cool gas or liquid, which is at a temperature below about 70.degree. C, on the Under-Film Thickness94and the Over-Film Thickness93as they exit the pinch point258or at any position outside of the pinch point258. The cooling process may be very rapid if, for example, liquid nitrogen or another cool substance that is at a temperature below 70.degree. C is sprayed on the heated Under-Film Thickness94and the heated Over-Film Thickness93after they exit the pinch point258or the cooling may be very slow by producing the un-oriented tube42on a warmed shaft74or within a warm gaseous environment90, wherein the warmed shaft74and/or the warmed gases are maintained at a temperature within the range of about 50 to 150.degree. C.

The Heated Tube Former256is operated within the gaseous environment90. It is preferred that the gaseous environment90comprises a Protective Environment. The Protective Environment minimizes or prevents the reduction of the degree of polymerization within the stent material(s)85and/or minimizes or prevents the reduction in efficacy of the active ingredient(s)34when the film thicknesses67are heated during the Heated Tube Former256process. In the preferred embodiment, the gaseous environment90is held at a temperature within the range of negative 100.degree. C to positive 100.degree. C. In other embodiments, the gaseous environment90is at higher or lower temperatures. The gases within the gaseous environment90may be circulated or exchanged with fresh gases. Alternatively, or additionally, interconnecting the Over-Film Thickness93to the Under-Film Thickness94may be achieved by employing ultrasonic welding, hot gas welding, hot plate welding, induction welding, dielectric welding, vibration welding as the film(s)66pass through the pinch point258or when at least part or the complete wall thickness45is held together under pressure in the shape of the un-oriented tube42. In an embodiment, the ultrasonic welding is achieved at a frequency within the range of 10 to 100 kHz for duration between greater than 0 to 25 seconds. In other embodiments, the ultrasonic welding is achieved at higher or lower frequencies.

FIG. 69depicts a Solvent Process Tube Former262. As depicted inFIG. 69, another method for interconnecting the film thicknesses67in the shape of a cylindrical-shaped tube comprises spraying a mist153comprising at least one solvent86and/or at least one glue comprising the liquid solution83onto at least one film major surface73at the interface between the Under-Film94and the Over-Film93just before the Over-Film93enters the pinch point258so that at least two film81thicknesses67are solvent bonded together, wherein the solution83comprises at least one stent material(s)85and at least one solvent86. In an embodiment, the mist153includes at least one active ingredient34. In another embodiment, the mist153excludes the active ingredient(s)34. The solid film(s)66may include the active ingredient(s)34positioned at least in one of the following positions: (1) within the solid film(s)66; (2) on at least one of the major surface(s)73of the solid film(s)66; (3) within the solvent(s)86; (4) within the liquid solution83that is being sprayed on at least one of the major surface(s)73of the solid film(s); (5) between at least two film thicknesses67; (6) on at least one major surface73facing the un-oriented tube42; or (7) on at least one major surface73facing the pinch roller257. A strong solvent86may be used at full strength or diluted with a weak solvent86to prevent dissolving the solid film(s)66or causing the solid film(s)66to tear while being fed into the Solvent Process Tube Former262.

Alternatively, or additionally, at least one of the solid films66are fed between the shaft74and the pinch roller257of the Solvent Process Tube Former262when at least one or all of the solid(s) film(s)66are swollen, wherein the swollen, solid film66comprises between greater than 0 wt. % and 80 wt. % solvent(s)86and the remainder of the swollen, solid film66comprises the stent material(s)85or stent material(s)85and the active ingredient(s)34. In other embodiments, the swollen, solid film66includes greater or lesser solvent(s)86. At least one of the swollen, solid film(s)66may include the active ingredients34positioned within the swollen, solid films66and/or on at least one of the major surface(s)73of the swollen, solid films66. In other embodiments, the swollen, solid film(s)66do not include the active ingredient(s)34. When the swollen, solid film(s)66are wrapped around the spinning shaft74the Over-Film Thickness93is interconnected to the Under-Film Thickness94because there is sufficient mobility of the molecules within the stent material(s)85within each film thickness67to allow at least one of the molecules or all of the molecules on the film major surfaces73to cross the knit line65so that when the solvent(s)86are removed from the swollen, solid film(s)66a bond is formed between the Over-Film thicknesses93and the Under-Film thicknesses94. The viscosity of the stent material(s)82that are within the swollen, solid film(s)66are very high so that there is very little mixing of the stent material(s)85that are located within the bulk of the Over-Film Thickness93and the Under-Film Thickness94. This means that if the Under-Film Thickness94comprises 94 different stent material(s)85or a different mixture of stent material(s)85and active ingredient(s)34than the over layer93, that discrete layer(s)51are formed within the wall thickness45of un-oriented tube42, which is converted into the oriented tube38and/or the stent10. Conversely, if the Under-Film Thickness94comprises 94 the same stent material(s)85or the same mixture of stent material(s)85and active ingredient(s)34as the over layer93, that one layer51comprising homogenous stent material(s)85or a homogeneous mixture of the stent material(s)85and the active ingredient(s)34is formed within the wall thickness45of un-oriented tube42. Since the layer(s)51are configured in the shape of the roll52that includes the transition95an a pattern where each film thickness67gets gradually farther from the central axis4of the un-oriented tube42, the layers52within the un-oriented tube42and/or the layers52within the stent10have a tendency to be non-concentric or slightly un-concentric when viewed from the end of the un-oriented tube42and or the stent10.

In one more embodiment of the Solvent Process Tube Former262, at least one swollen, solid film66and at least one dry, solid film66are fed between the shaft74and the pinch roller257of the Solvent Un-Oriented Tube Former262, wherein the swollen, solid film(s)66comprise between greater than 0 wt. % and 80 wt. % solvent(s)86and the remainder of the swollen, solid film(s)66comprise the stent material(s)85or the stent material(s)85and the active ingredient(s)34and the dry, solid film(s)66comprises between 0 wt. % and 10 wt. % solvent(s)86and the remainder of the dry, solid film(s)66comprise the stent material(s)85or stent material(s)85and the active ingredient(s)34. In other embodiments, the swollen, solid film(s)66and/or the dry, solid film(s)66include higher and/or lower weight percentage of the solvent(s)86. At least one of the swollen, solid film(s)66and/or the dry, solid film(s)66may include the active ingredient(s)34positioned within the solid film(s)66and/or on at least one of the major surface(s)73of the solid film(s)66. When there are multiple dry solid film(s) fed into the Solvent Process Tube Former262, it is preferred to have at least one swollen, solid film66adjacent to each dry, solid film66. In other embodiments, the swollen, solid film(s)66and/or the dry, solid film(s)66do not include the active ingredient(s)34. When the swollen, solid film(s)66and the dry, solid film(s)66are wrapped around the spinning shaft74the Over-Film Thickness93is interconnected to the Under-Film Thickness94because there is sufficient mobility of the molecules within the stent material(s)85in the swollen, solid film thickness67to allow at least one molecule or all of the molecules on the films' major surfaces73to cross the knit line(s)65so that when the solvent(s)86are removed from the swollen, solid film(s)66a bond is formed between the Over-Film thicknesses93and the Under-Film thicknesses94. Passing the swollen, solid film66and the dry, solid film through the pinch point258applies pressure on at least the two adjacent solid films66as the solid films66are wrapped around the shaft74, which facilitates interconnecting the Under-Film thicknesses94and the Over-Film thicknesses93. In another embodiment of the Solvent Process Tube Former69, there may be sufficient tension within the solid film(s)66being wrapped around the shaft74that it is unnecessary to use the pinch roller257. In one more embodiment, the shaft74may be stationary and the solid film(s)66may be wrapped around the shaft74by the solid film(s)66articulating around the shaft73in a motion that forms the roll52or the Roll Including Active Ingredient(s)143on the shaft outer surface78.

Alternatively, or additionally, in another embodiment, at least one swollen, solid film66and/or at least one dry, solid film66are fed between the shaft74and the pinch roller257of the Solvent Tube Former262, wherein the swollen, solid film66and/or the dry, solid film66are elongated in the machine direction79and/or widened in the transverse direction80or elongated and widened in the biaxial direction81prior to being wrapped around the shaft74. At least one of the swollen, solid films66and/or the dry, solid films66may include the active ingredient(s)34positioned within the swollen, solid films66and/or within the dry, solid films66and/or on at least one of the major surface(s)73of the swollen, solid films66and/or the dry, solid films66. In other embodiments, the swollen, solid film(s)66and/or the dry, solid film(s)66do not include the active ingredient(s)34. Elongating and/or widening the swollen, solid film(s)66and/or the dry, solid film(s)66strains the solid films66in the direction of strain just before wrapping the swollen, solid film(s)66and/or the dry, solid film(s) around the shaft74, which converts the solid film(s)66into the oriented solid films66that include molecular orientation in the direction of strain. Orientation of the stent material's85molecules that are positioned within the solid films66strengthens the solid film(s)66in the direction of strain.

When the oriented, solid film(s)66are wrapped around the spinning shaft74the Over-Film Thickness93is interconnected to the Under-Film Thickness94because there is sufficient mobility of the molecules within the stent material(s)85within the swollen, solid film thickness67to allow at least one molecule or all of the molecules on the film major surfaces73of the swollen, solid film(s)66to cross the knit line(s)65so that when the solvent(s)86are removed from the swollen, solid film(s)66a bond is formed between the Over-Film thicknesses93and the Under-Film thicknesses94, which results in the formation of the oriented tube38. In an embodiment, the solid film(s)66are elongated and widened the same amount; in an embodiment, the solid film(s)66are elongated more than widened; and in an embodiment the solid film(s)66are widened more than elongated. If the solid film(s)66are aligned within the wall thickness of the roll52or the Roll Including Active Ingredient(s)143so that the central axis of the solid film(s)70is perpendicular to the central axis77of the shaft74, elongating the solid film(s)66increases the radial strength of the stent10and widening the solid film(s)66increase the longitudinal strength of the stent10. In this embodiment of the Solvent Process Tube Former262, the oriented tube38is formed because the molecular orientation imparted in the solid film(s)66is at least partially or completely retained within the wall thickness27of the oriented tube38being formed on the shaft74. It is believed that the more quickly that the residual solvent(s)86are removed from the oriented tube38the more molecular orientation that is retained within the oriented tube wall thickness27, which means that the more quickly the solvent(s) are removed from the oriented tube wall thickness27the stronger the oriented tube38becomes. Warming the oriented tube38and/or placing the oriented tube38under a vacuum to dry the oriented tube38may increase the rate removal of the solvent(s)86from the oriented tube38. To avoid excessive loss of molecular orientation of the stent material(s)85within the oriented tube38, it is believed that the oriented tube38should not be heated above the glass transition temperature (Tg) of at least one of the stent material(s)85comprising the oriented tube38after the film(s)85have been wrapped around shaft74, more narrowly not above 120.degree. C. It is preferred to heat the oriented tube38on the shaft74within the Protective Environment during solvent(s)86removal. The oriented tube38may be dried, for example, in a vacuum dryer or desiccant dryer for greater than 15 seconds to 90 days, more narrowly between 5 minutes to 24 hours at between greater than 0 to 120.degree. C at a low vacuum less than 0.01 MPa. It is preferred to dry the oriented tube38on the shaft74until the solvent(s)86content within the oriented tube38is reduced to less than 500 ppm. In other embodiments, the oriented tube74is dried on the shaft74until it contains equal to or greater than 500 ppm solvent(s)86. The swollen, solid film66tends to dry quickly when elongated and/or widened, which can result in a low concentration of the solvent(s)86within the solid films66prior to wrapping. To avoid lowering the amount of solvent(s)86within the solid film(s)66to a point that is lower than what is required to interconnect the adjacent wrapped film(s)66, the gaseous environment90may be maintained at a cool temperature that slows the evaporation of the solvent(s)86and/or the solvent86concentration within the gaseous environment90or the relative humidity of the gaseous environment90may be kept at a high level to slow down the evaporation of the solvent(s)86while the solid films66are being conveyed to the pinch point258and while the solid film(s)86are being wrapped around the shaft74. The solvent86concentration within the gaseous environment90may be maintained to comprise between greater than 0% to 60% solvent and the remainder of the gaseous environment90comprise gas and/or the relative humidity of the gaseous environment90may be maintained to comprise greater than 0% to 90% moisture and the remainder of the gaseous environment90comprise gas. In other embodiments, the solvent86concentration within the gaseous environment90and/or the relative humidity within the gaseous environment90are higher. Increasing the pressure of the gaseous environment90may also slow down the evaporation of the solvent(s)86that are within the solid film(s)86. The pressure of the gaseous environment90may be held between 0.1 MPa to 100 MPa during conveyance of the solid films66to the pinch point258and/or while the solid film(s)66are being wrapped around the shaft74. In other embodiments the gaseous environment90is held at lower or higher pressures during conveyance of the solid films66to the pinch point258and/or while the solid film(s)66are being wrapped around the shaft74.

The Solvent Process Tube Former262is operated within the gaseous environment90. It is preferred that the gaseous environment90comprises a Protective Environment. In the preferred embodiment, the gaseous environment90is held at a temperature within the range of negative 100.degree. C to positive 100.degree. C, more narrowly room temperature. The gases within the gaseous environment90may be circulated or exchanged with fresh gases to facilitate removal of the solvent(s)86from the oriented tube wall thickness27or the un-oriented tube wall thickness45. Fresh gases comprise virgin gases or recycled gases, wherein at least part of the volatile solvent(s)86that are removed from the solid film(s)66are removed from the gases. The removed solvent(s)86may be reused within the Solvent Process Tube Former262.

The swollen, solid film(s)66and/or the dry, solid film(s)66may be under tension in the machine direction79, transverse direction80or the biaxial direction81by applying a load within the range of greater than 0 MPa to 40 MPa on the swollen, solid film(s)66, the dry, solid film(s)66and/or the softened, solid film(s)66prior to passing the solid film(s)66through the pinch point258and/or when wrapping the solid film(s)66around the shaft74. In other embodiments, the tension within the solid film(s)66may be achieved by applying a load to the solid film(s)66that is equal to or greater than 40 MPa.

In an embodiment, passing the Under-Film Thickness94and the Over-Film Thickness93through the pinch point258applies pressure on the film thicknesses67, which facilitates creation of a bond between the Over-Film Thickness93and the Under-Film thicknesses94. The shaft67may rotate at greater than 0 to 10,000 revolutions per minute (“RPM”) so that the film thicknesses93are heated just long enough to thermally weld the film thicknesses93together as they pass between the two cylinders or pinch point258, which results in forming the un-oriented tube42around the shaft74when there have been sufficient wraps interconnected to produce a wall thickness45of sufficient thickness13to produce the stent40. Depending on the thickness of the film(s)67, there could be between 2 to about 1000 wraps of the film(s)66required to produce the un-oriented tube42using the Heated Tube Former256method or the Solvent Tube Former262method. In an embodiment, at least one of the film major surfaces73is at least partially or completely covered with the active ingredient(s)34within the Active Ingredient Storage Area141prior to feeding the solid film(s)66between the shaft74and the pinch roller257and/or wrapping the solid film(s)66around the shaft74so that the active ingredient(s)34are positioned between at least two wraps of film66, which results the active ingredient(s)34being positioned between two film thicknesses67excluding the active ingredient(s)34that are welded together like the example depicted inFIG. 49or other embodiments described herein. Alternatively, or additionally the active ingredient(s)34are positioned within the film thickness67of at least one of the solid films66so that the active ingredient(s)34are positioned within the Roll Including Active Ingredient(s)143. The short duration of the contact of the heated pinch roller257on the solid film thicknesses67and the active ingredient(s)34maintains at least part of or the entire efficacy of the active ingredient(s)82. Welding the solid film(s)66under the Protective Environment, for example within an inert gas, also at least partially or completely preserves the efficacy of the active ingredient(s)34and the stent material's85degree of polymerization. The Heated Tube Former256method or the Solvent Tube Former262methods of forming the un-oriented tube42or the oriented tube38from the solid film(s)66interconnects the film thicknesses67without exposing the active ingredient(s)34to a long heating cycle, which at least partially or completely preserves the efficacy of the active ingredient(s)272that are incorporated into the stent10.

Alternatively, heating the roll52or the Roll Including Active Ingredient (s)143in an oven forms the un-oriented tube42. The un-oriented tube42may be formed by following these steps: (1) preparing at least one solid film66that includes or excludes the active ingredient(s)34; (2) wrapping at least one solid film66that includes or excludes the active ingredient(s)34around the shaft74to produce the roll52or the Roll Including Active Ingredient(s)143; (3) placing the roll52or the Roll Including Active Ingredient(s)143while conforming to the shaft74outer surface78in an oven or in a pre-heated oven that is at least partially or fully comprises the gaseous environment90that preferably comprises the Protective Environment; (4) heating the roll52or the Roll Including Active Ingredient(s)143while still positioned on the shaft74within the oven that is maintained at a temperature within the range of greater than 0.degree. C to 250.degree. C for between greater than 0 seconds to 30 minutes; (5) removing the roll52and/or the Roll Including Active Ingredient(s)143while positioned on the shaft74from the oven; (6) cooling the roll52or the Roll Including Active Ingredient(s)143on the shaft74to a temperature below 65.degree. C or to normal room temperature (about 23-23.degree C.) within greater than 0 seconds to 60 minutes; and (7) removing the un-oriented tube74from the shaft74. The un-oriented tube42that was formed in the oven and cooled on the shaft74is converted into the oriented tube38and/or the stent10. In an embodiment, heating the roll52or the Roll Including Active Ingredient(s)143while positioned on the shaft74interconnects the various film thicknesses67by bonding the film thicknesses67together or sintering the film thicknesses67together forming the un-oriented tube42.

The Heated Tube Former256, the Solvent Process Tube Former262and the heating the roll52or Roll Including Active Ingredient(s)143on the shaft52in the oven methods of producing the un-oriented tube42and/or the oriented tube38form discrete layers51within the wall thickness45or wall thickness27when the adjacent film thicknesses67comprises different stent material(s)85or when one film thickness67includes the active ingredient(s)34and the adjacent film thickness67does not include the active ingredient(s)34or when the adjacent film thicknesses67include a different quantity of the active ingredient(s)34or when the adjacent film thicknesses67include different active ingredient(s)34or when the adjacent film thicknesses67include a different combination of the active ingredient(s)34. The discrete layers51are formed because the viscosity of the solid films66when in dry form, swollen form, softened form or melted form only permit minor mixing of the stent material(s)85at the molecule level within the bond(s)65. In these embodiments, most of the stent material(s)85(the “bulk”) within the film thicknesses67do not intermix, which results in formation of discrete layer(s)51in the stent10wall thickness13. In an embodiment, the mixing of the stent material(s)85is minor because there is virtually no shear between the adjacent film thicknesses67when they are interconnected. In these embodiments, the adjacent film thicknesses67are arranged in a roll configuration and statically joined by a mechanism wherein at least some of the molecules within the stent material(s)85in each film thickness67are mobilized by softening the adjacent film thicknesses67by heating the film thicknesses67or including at least one solvent86within at least one of the solid films66so that at least some the molecules within each of the film thicknesses67at least partially move or migrate across the bond(s)65in a way that ties the two separate film thicknesses67together when the assembly is cooled and/or the solvent(s)86are at least partially or completely removed from the wall thickness45or the wall thickness27. In an embodiment, to prevent shearing of the assembled film thicknesses67, the pinch roller257applies less than 500 Newton's on the solid film(s)66being wrapped around the shaft74.

FIG. 70throughFIG. 75depict two embodiments of portions of the wall thickness13of the linear ring struts20and the link struts21. Referring toFIG. 70, which depicts a cross sectional view of the stent10wall thickness13, in an embodiment the wall thickness13may be divided into four discrete layers51, wherein the layer51-A is positioned closest to the outer surface16, the layer51-B is positioned underneath layer51-A, the layer51-C is positioned underneath layer51-B, and the layer51-D is positioned closest to the inner surface17or underneath layer51-C. As depicted inFIG. 71, which depicts a cross sectional view of the stent10wall thickness13, in another embodiment the wall thickness13may be divided into four discrete layers51, wherein the layer51-A is positioned closest to the inner surface17, the layer51-B is positioned on top of layer51-A, the layer51-C is positioned on top of layer51-B, and the layer51-D is positioned closest to the outer surface16or on top of layer51-C. In embodiments wherein the layers51are arranged as depicted inFIG. 70andFIG. 71, the stent material(s)85comprising layer51-A may degrade and/or resorb faster than the stent material(s)85comprising layer51-B, the stent material(s)85comprising layer51-B may degrade and/or resorb faster than the stent material(s)85comprising layer51-C, and the stent material(s)85comprising layer51-C may degrade and/or resorb faster than the stent material(s)85comprising layer51-D. Alternatively, or additionally, in embodiments wherein the layers51are arranged as depicted inFIG. 70andFIG. 71, the stent material(s)85comprising layer51-A may comprise a lower weight average molecular weight than the stent material(s)85comprising layer51-B, the stent material(s)85comprising layer51-B may comprise a lower weight average molecular weight than the stent material(s)85comprising layer51-C, and the stent material(s)85comprising layer51-C may comprise a lower weight average molecular weight than the stent material(s)85comprising layer51-D. The layer51-A, the layer51-B, the layer51-C and the layer51-D depicted inFIG. 70andFIG. 71are formed from at least one or multiple film thicknesses67. AlthoughFIG. 70andFIG. 71depict the layer51-A, the layer51-B, the layer51-C and the layer51-D as having the same layer thickness91, in other embodiments at least one or all the layer51thicknesses91are a different layer thickness91than at least one or all the other layer thicknesses91within the wall thickness13. Although,FIG. 70andFIG. 71depict four layers51, in other embodiments there may be greater than or less than four layers51within the wall thickness13, wherein the degradation rate and/or the weight average molecular weight of the stent material(s)85decrease layer-by-layer starting with the layer51that is positioned on the outer surface16having the fastest degradation rate and/or the lowest weight average molecular weight and ending with the layer51that is positioned on the inner surface17having the slowest degradation rate and/or the highest weight average molecular weight, or the opposite. It should be appreciated that the embodiments depicted inFIG. 70andFIG. 71may include the active ingredient(s)34having at least one or all the positions selected from the group of: (1) between at least two or all the layer thicknesses91; (2) between at least two or all the film thicknesses67; (3) within at least one or all the layer thicknesses91; or (4) within at least one or all of the film thicknesses67. The active ingredient(s)34within each of the layers51may comprise the same or different chemical composition and/or the same or different active ingredient(s)'34dosage.

In an embodiment, the layer51-A and the layer51-D are barrier layers51that exclude the active ingredient(s)34and the layer51-B and the layer51-C are therapeutic layers51that include the active ingredient(s)34. Additionally, the wall thickness13may optionally include the coating30that includes additional active ingredient(s)34positioned on at least the outer surface16. The barrier layers51are useful for enabling the stent10to provide radial support to the anatomical lumen36until the anatomical lumen36is self-supporting and the barrier layers51also delay or slow down the delivery of the active ingredient(s)34stored within and/or between the therapeutic layers51or between the therapeutic layer(s)51and the barrier layers51by at least temporarily protecting the therapeutic layers51from erosion and placing an additional thickness of the stent material(s)85between the therapeutic layer(s)51and the anatomical lumen36that the active ingredient(s)36must pass through to reach the anatomical lumen36. Alternatively, the layer51-A and the layer51-C may be therapeutic layers51and the layer51-B and the layer51-C may be the barrier layers51. In yet one more embodiment, layer51-A and the layer51-D may be therapeutic layers51and the layer51B and the layer51-C may be the barrier layers51. It should be appreciated that the wall thicknesses13depicted inFIG. 70andFIG. 71that include barrier layer(s)51and therapeutic layer(s)51are not limited to an embodiment having four layers51and that other embodiments having the same configurations may be made having less than four or greater than four layers51.

As depicted inFIG. 72throughFIG. 75, which depict cross sectional views of the stent10wall thickness13, the wall thickness13may be divided into three discrete layers51. As depicted inFIG. 72andFIG. 73, in an embodiment the layer51-A and the layer51-C may be thicker than the layer51-B. In other embodiments, as depicted inFIG. 74inFIG. 75, the layer51-B may be thicker than layer51-A and layer51-C. Although not depicted, in other embodiments the layer51-C may be thicker than layer51-B and the layer51-B may be thicker than layer51-A, or the opposite. In one more embodiment, the layer51-A, the layer51-B and the layer51-C comprise substantially the same thickness91. The layer thicknesses91may be arranged within the stent10wall thickness13in any possible combination or permutation. For example, using the pattern format (closest to outer surface16, middle of wall thickness13, closet to inner surface17) the layers91may be arranged in at least one configuration selected from the group: (1) thinnest layer51, thicker layer51, thickest layer51; (2) thinnest layer51, thickest layer51, thicker layer51, (3) thicker layer51, thinnest layer51, thickest layer51; (4) thicker layer51, thickest layer51, thinnest layer51; (5) thickest layer51, thicker layer51, thinnest layer51; or (6) thickest layer51, thinnest layer51, thicker layer51, wherein the thickest layer51is greater than the thicker layer91and the thicker layer51is greater than the thinnest layer51. Although,FIG. 72throughFIG. 75depict three layers51, in other embodiments there may be greater than or less than three layers51, wherein the layer thickness91is different in at least one of the layers51than the other layers51. It should be appreciated that the embodiments depicted inFIG. 72throughFIG. 75may include the active ingredient(s)34having at least one position or all of the positions selected from the group of: (1) between at least two layer thicknesses91; (2) between at least two film thicknesses67; (3) within at least one or all of the layer thicknesses91; (4) within at least one or all of the film thicknesses67; (5) on the outer surface16or (6) on the inner surface17. The therapeutic layer(s)51and/or the therapeutic film thicknesses67may be separated by at least one of the barrier layers51or the barrier film thicknesses67. The active ingredient(s)34within each of the layers51may comprise the same or different chemical composition and/or the same or different active ingredient(s)34dosage. In an embodiment, the dosage of the active ingredient(s)34within each discrete layer51is the same so that as each layer51is resorbed the same amount of the active ingredient(s)34are delivered to the anatomical lumen36during resorption of all the layers51and in another embodiment, at least one or all of the layers51contain a different dosage of the active ingredient(s)34within each discrete layer51so that as each layer51is resorbed a different amount of the active ingredient(s)34is delivered to the anatomical lumen36during the resorption of each layer51. In one more embodiment, the dosage of the active ingredient(s)34within each layer51is proportional to the mass of the stent material(s)85within each layer51. For example, if the wall thickness13configuration depicted inFIG. 72has 40% of the stent material'(s) 85 mass located with the layer51-A, 20% of the stent material'(s) 85 mass located with the layer51-B and 40% of the stent material'(s) 85 mass located with the layer51-C, the stent wall thickness13would have 40% of the active ingredient'(s) 34 mass located within the layer51-A, 20% of the active ingredient'(s) 34 mass located with the layer51-B and 40% of the active ingredient'(s) 34 mass located with the layer51-C. In another embodiment, the dosage of the active ingredient(s)34within each layer51is disproportionate to the mass of the stent material(s)85within each layer51. For example, the layer51comprising at least one part faster degrading stent material(s)85may include a higher dosage than the layer51comprising at least one part slower degrading stent material(s)85or the layer51comprising at least one part the stent material(s)85that comprising glycolide may include a higher dosage of the active ingredient(s)34than the stent material(s)85comprising homopolymers of L-lactide. The release of the active ingredient(s)34that are positioned within the layers51at least partially or completely reduce the risk of side effects of the stent material(s)85resorbing during the duration of the resorption process. For example, the active ingredient(s)34prevent restenosis and/or device thrombosis at least during the duration that the stent10is implanted within the anatomical lumen36and/or during the resorption time.

In an embodiment of the wall thickness13depicted inFIG. 72throughFIG. 75, the layer51-A and the layer51-C (outer layers51) may comprise the stent material(s)85that degrade and/or resorb slower than the stent material(s)85comprising layer51-B (middle layer51). When at least two layers51comprised of slower degrading and/or resorbing stent material(s)85are separated by at least one layer51of faster degrading stent material(s)85, the wall thickness13of the implanted stent10may delaminate within the anatomical lumen36, which results in the entire implanted stent10resorbing faster than if the implanted stent10that does not delaminate within the anatomical lumen36because the delaminated wall thickness13has more surface area exposed to the contents6, cells and/or tissue surrounding the implanted wall thickness13that degrade the stent material(s)85within the stent10. In an embodiment that results in a delaminated implanted wall thickness13, the implanted stent's10wall thickness13delaminates because the faster degrading and/or resorbing layer51weakens, erodes and/or losses mass in a way that the two adjacent layers51comprising the slower degrading and/or resorbing stent material(s)85become at least partially or completely disconnected within the anatomical lumen36, which results in at least partial or complete separation of the two slower degrading and/or resorbing layers51. Additionally, the tissue and cells surrounding the implanted stent10may grow within the delaminated wall thickness13, which may result in reinforcement of the stent10and/or acceleration of the resorption of the remaining mass of the stent material(s) that are within the anatomical lumen36. When the faster degrading and/or resorbing layer51includes the active ingredient(s)34, the active ingredient(s)34within the faster degrading and/or resorbing layer51may be partially or completely released before the active ingredient(s)34located within the slower degrading and/or resorbing layers51. The slower degrading and/or resorbing layer51-A and layer51-C may at least partially protect the faster degrading and/or resorbing layer51-B against the content(s)6, cell and tissue surrounding the implanted stent10that cause degradation and/or resorption of the stent10so that the stent10can provide support to the anatomical lumen36until the anatomical lumen36is substantially self-supporting. The stent's10capability supporting the anatomical lumen36can be determined by measuring lumen loss after implantation of the stent10within the anatomical lumen36. The slower degrading and/or resorbing layer51-A and layer51-C may, for example, at least temporarily protects the faster degrading and/or resorbing layer51against hydrolysis by slowing the entry of water into the faster degrading and/or resorbing layer51. Slowing the penetration of water into the faster degrading and/or resorbing layer51delays the loss of mechanical strength of the stent10, which enables the stent10to mechanically support the anatomical lumen36until the anatomical lumen36has healed from the injury it experiences during implantation of the stent10within the anatomical lumen36and/or until the anatomical lumen36become self-supporting. In an embodiment, after the anatomical lumen no longer needs support from the stent10, the stent10may be rapidly resorbed.

The stent10may retain sufficient strength to support and/or substantially hold open the anatomical lumen36for a duration starting from the time of the stent10implantation within the anatomical lumen36selected from the group of: (1) greater than 0 to 30 days, (2) greater than 0 to 60 days, (3) greater than 0 to 90 days, (4) greater than 0 to 120 days, (5) greater 0 to 150 days or (6) greater than 0 to 180 days, (7) greater than 0 to 210 days, (8) greater than 0 to 240 days, (9) greater than 0 to 270 days, (10) greater than 0 to 300 days, (11) greater than 0 to 330 days or (12) greater than 0 to 360 days. In other embodiments, the stent10may retain sufficient strength to support and/or hold open the anatomical lumen35for a longer time. For a vascular stent10, it is preferred that the stent10be capable of providing support to the anatomical lumen36for between about 5 days to about 180 days after the stent10is implanted within the anatomical lumen36.

The mass of the stent10may resorbed within a duration starting from the time of the stent10implantation within the anatomical lumen36selected from the group of: (1) greater than 0 to 30 days, (2) greater than 0 to 60 days, (3) greater than 0 to 90 days, (4) greater than 0 to 120 days, (5) greater 0 to 150 days or (6) greater than 0 to 180 days, (7) greater than 0 to 210 days, (8) greater than 0 to 240 days, (9) greater than 0 to 270 days, (10) greater than 0 to 300 days, (11) greater than 0 to 330 days, (12) greater than 0 to 360 days, (13) greater than 0 to 390 days, (14) greater than 0 to 420 days, (15) greater than 0 to 450 days, (16) greater than 0 to 480 days, (17) greater to 0 to 510 days, (18) greater than 0 to 540 days, (19) greater than 0 to 570 days, (20) greater than 0 to 600 days, (21) greater than 0 to 630 days, (22) greater than 0 to 660 days, (23) greater than 0 to 690 days, (24) greater than 0 to 720 days, (25) greater than 0 to 750 days, (26) greater than 0 to 780 days, (27) greater than 0 to 810 days, (28) greater than 0 to 840 days, (29) greater than 0 to 870 days), (30) greater than 0 to 900 days, (31) greater than 0 to 930 days, (32) greater than 0 to 960 days, (33) greater than 0 to 990 days, (34) greater than 0 to 1,020 days, greater than 0 to 1,050 days, or (35) greater than 0 to 1,080 days or greater than 0 to 1,110 days. In other embodiments, the mass of the stent10may resorbed within a longer duration than 1,110 days to no longer than 5 years.

In an embodiment, the stent10includes a Stent-To-Anatomical Lumen Coverage Area (“STALCA”) within the range of greater than 0.0% to about less than 99.0%, more preferably in the range of about 0.5% to 45.0%, and most preferably in the range of 0.5% to equal to or less than about 25.0% or whatever is experimentally determined to be the optimum STALCA for the end-use application determined by those skilled in the art. In other embodiments, the stent10includes a STALCA equal to or greater than ninety percent. The STALCA equals the surface area of the stent's40outer surface16area divided by the surface area of the anatomical lumen36within the treatment site35. In an embodiment, for example, the stent10has a STALCA less than 25%, which means that at least 75% of the mass of the un-oriented tube42or the oriented tube38is removed when the strut pattern171is cut into the un-oriented tube42or the oriented tube38. In an embodiment, the stent10has a volume within the range of greater than 0 cubic millimeters to 2463 cubic millimeters or 2.463 cubic centimeters (“cm3”). Therefore, in an embodiment the stent10comprising the stent material(s)85having a nominal density of 1.3 g/cm3, the maximum stent10mass equals about 3.2 g. In other embodiments, comprising less dense or more dense stent10material(s)85the mass of the stent10may be higher or lower. For, example, if the stent10including reinforcements240comprising metal elements, the maximum mass of the stent10is greater than 3.2 g. The mass of a typical stent10used in a coronary artery, however, is much lower. For example, if the stent10is produced within the portion of the oriented tube38depicted on row15of the table inFIG. 110, which has the inner diameter equal to 3 mm, the wall thickness equal to 0.080 mm and the length equal to 18 mm, the stent10comprised of the stent10material(s)85having density of 1.3 g/cm3, the stent10has a mass equal to or about 0.0045 g when the stent10has the STALCA equal to 25%. The mass of this embodiment of the stent10is calculated by 0.013934 cm3.times.1.3 g/cm3.times.0.25=0.0045 g. In other embodiments, the stent10used in a coronary artery may have higher or lower stent10mass. For example, stents10having a smaller inner diameter12, smaller wall thickness13, shorter length and/or lower STALCA would have a lower stent mass than 0.0045 g or stents10having a larger inner diameter12, larger wall thickness13, longer length15and/or higher STALC would have a higher stent mass than 0.0045 g. Other factors may also affect the mass of the stent10. For example, a stent10comprising stent material(s)85having a higher degree of crystallinity will have a higher stent mass than a stent10comprising stent material(s) having a lower degree of crystallinity. For example, the density of poly (L-lactide) can vary between 1.1 g/cm3 to 1.5 g/cm3 depending on the degree of crystallinity, wherein 1.1 g/cm3 is for more amorphous poly (L-lactide) and 1.5 g/cm3 is for more crystalline poly (L-lactide). Moreover, the mass of the stent10may be affected by blending of multiple stent material(s)85during formation of the stent10. For example, blending of poly (L-lactide) having a nominal density of 1.3 with poly (glycolide) having a nominal density of 1.53 g/cm3 may increase the mass of the stent10or blending of poly (L-lactide) having a nominal density of 1.3 g/cm3 with poly (caprolactone) having a nominal density of 1.145 g/cm3 may decrease the mass of the stent10. Likewise, inclusion of reinforcements240comprising a magnesium alloy having a nominal density between 1.7 g/cm3 to 2.3 g/cm3 within poly (L-lactide) having a nominal density within the range of 1.2 g/cm3 to 1.5 g/cm3 or other stent material(s)85will increase the density of the stent10. Alternatively or additionally, adding at least one active ingredient34to the stent material(s)85may increase or decrease the mass of the stent10. For example, including the active ingredient34Sirolimus, which has a density of about 1.2 g/cm3, would have a negligible impact on the mass of the stent10comprised of poly (L-lactide) having a low degree of crystallinity.

The implanted stent10wall thickness13may be configured to distribute at least one of the active ingredients34between the implanted linear ring struts20, link struts21and/or adjacent to the rings19located on the proximal end25and distal end26of the stent10. At least one active ingredient34may migrate away from the deployed location of the stent10in an embodiment of the implanted stent10that delaminates within the anatomical lumen36, wherein the deployed location of the stent10is the location of the stent10immediately after the catheter37completes compressing the stent10against the interior of the anatomical lumen36. In an embodiment, at least one of the released active ingredient(s)34is distributed and at least partially retained within region of the implanted linear ring struts20and/or link struts21until at least the mass of the stent10is partially or completely resorbed. The stent10may be configured to release the active ingredient(s)34from the stent10so that the active ingredient(s)34spread to a distance of about between 0.0 mm to 1 mm away from the implanted linear ring strut20and/or link strut21. In other embodiments, the stent10may be configured to release at least one of the active ingredient(s)34so that the active ingredient(s)34are distributed and at least partially retained within at least part of the region between greater than 0 mm to about 5 mm surrounding the implanted linear ring struts20and/or link struts21until the mass of the stent10is partially or completely resorbed. In an embodiment, the stent10is configured to release at least one of the active ingredient(s)34so that the active ingredient(s)34are distributed and/or at least partially retained within the tissue and/or cells positioned on the abluminal side of the implanted stent10at least until the stent10is partially or completely resorbed. In another embodiment, the stent10is configured to release the active ingredient(s)34so that the active ingredient(s)34are distributed and at least partially retained within the tissue and/or cells positioned on the luminal side of the implanted stent10at least until the stent10is partially or completely resorbed. In one more embodiment, the stent10is configured to release the active ingredient(s)34so that the active ingredient(s)34are distributed and at least partially retained within the tissue and/or cells positioned on the luminal side and the abluminal side of the implanted stent10at least until the stent10is partially or completely resorbed. In an embodiment, the wall thickness13is capable of releasing at least one part of the active ingredient(s)34located within the faster degrading and/or resorbing layer51after the endothelial cells at least partially or completely cover the linear ring struts20and/or the link struts21, which prevents part or all of the active ingredient(s)34that are released from the stent10from being washed away by the content(s)6so that there is at least one active ingredient34at least temporarily retained within the area surrounding the linear ring strut(s)20and/or link strut(s)21until the mass of the stent10is resorbed.

In another embodiment of the wall thickness13depicted inFIG. 72throughFIG. 75, the stent material(s)85that comprise the layer51-A degrade and/or resorb faster than the stent material(s)85that comprise the layer51-B and the stent material(s)85that comprise layer51-B degrade and/or resorb faster than the stent material(s)85that comprise the layer51-C, or the opposite. In one more embodiment of the wall thickness13depicted inFIG. 72throughFIG. 75, the layer51-A may comprise the stent material(s)85that have a lower weight average molecular weight than the stent material(s)85that comprise the layer51-B and the stent material(s)85that comprise the layer51-B may comprise the stent material(s)85that have a lower weight average molecular weight than the stent material(s)85that comprise the layer51-C, or the opposite. Therefore, the layers51within the wall thickness13of the stent10may resorb and/or erode sequentially, wherein the abluminal layer51is substantially resorbed and/or eroded first, the middle layer51is substantially resorbed and/or eroded second and the luminal layer51is substantially resorbed and/or eroded last, or the opposite. In another embodiment, the luminal layer51has a higher crystallinity that the abluminal layer(s)51. Even thoughFIG. 72throughFIG. 75depict the stent10wall thickness13having three layers51, in other embodiments the stent10wall thickness13comprises greater than or less than three layers51, wherein the layers51within the wall thickness13of the stent10may resorb or erode sequentially in a way that the abluminal layer51is substantially resorbed or eroded first, the middle layers51(if present) are sequentially resorbed or eroded next and the luminal layer51is resorbed or eroded last, or the opposite. In the embodiments of the stent10comprising sequentially resorbing or eroding layers51, at least one or all the layer(s)51include at least one active ingredient34that is sequentially delivered to the anatomical lumen36as the layers51resorb and/or erode. In another embodiment, the luminal layer51within the stent10degrades slower than the abluminal layer(s)51because the stent material(s)85within the luminal layer51have a higher degree of crystallinity than the stent material(s)85within the abluminal layer(s)51. The quantity of the stent material(s)85resorbed over time may be controlled by the thickness91of the layers51. To produce the stent10wherein the mass of the layer(s)51resorb at approximately the same time, the layer(s)51comprising slower degrading rate stent material(s)85should be thinner than the layer(s)51comprising the fast-degrading rate stent material(s)85.

In an embodiment, the stent10wall thickness13comprises at least one therapeutic layer51and one barrier layer51, wherein the therapeutic layer51comprises a mixture of at least one stent material85and at least one active ingredient34and the barrier layer51comprises at least one stent material85. In an embodiment, the therapeutic layer51is positioned between two barrier layers51. In an embodiment, at least one barrier layer51is positioned between the inner surface17and the therapeutic layer51so that the barrier layer51at least partially or completely inhibits the delivery of the active ingredient(s)34to the anatomical lumen36that are within the therapeutic layer51of the implanted stent10until the barrier layer51is at least partially or completely resorbed. Alternatively, or additionally, in an embodiment, at least one barrier layer51is positioned between the outer surface16and the therapeutic layer51so that the barrier layer51at least partially or completely inhibits the delivery of the active ingredient(s)34to the anatomical lumen36that are within the therapeutic layer51of the implanted stent10until the barrier layer51is at least partially or completely resorbed. The inhibition of the delivery of the active ingredient(s)34facilitates delivering the optimum dosage of the active ingredient(s)34during the duration that the mass of the stent10is within the anatomical lumen36. In other embodiments, there may be two barrier layers51, three barrier layers51, four barrier layers51, five barrier layers51and so on between and/or surrounding each therapeutic layer51. Alternatively, or additionally, in other embodiments there may be two therapeutic layers51, three therapeutic layers51, four therapeutic layers51, five therapeutic layers51, or so on between and/or surrounding each barrier layer51. The therapeutic layer(s)51and the barrier layer(s)51may comprise the same or different stent material(s)85. In other embodiments, (1) the therapeutic layer(s)51may be the same thickness91as the barrier layer(s)51, (2) at least one of therapeutic layer(s)51may be thicker than at least one of the barrier layer(s)51, (3) at least one barrier layers51may be thicker than at least one of the therapeutic layer(s)51, (4) at least one barrier layer51may be thicker than at least one other barrier layer51, and/or (5) at least one therapeutic layer51may be thicker than at least one other therapeutic layer51.

FIG. 76throughFIG. 93depict various cross-sectional views of embodiments of the wall thickness13of the linear ring struts20and/or the link struts21, wherein the wall thickness13comprises multiple interconnected film thicknesses67.FIG. 76, depicts the wall thickness13of the linear ring struts20and/or the link struts21, wherein the wall thickness13comprises two interconnected film thicknesses67comprising the same stent material(s)85. The two film thicknesses67are interconnected with one bond65.FIG. 77, depicts the wall thickness13of the linear ring struts20and/or the link struts21, wherein the wall thickness13comprises three interconnected film thicknesses67comprising the same stent material(s)85. The three film thicknesses67are interconnected with two bonds65.FIG. 78, depicts the wall thickness13of the linear ring struts20and/or the link struts21, wherein the wall thickness13comprises four interconnected film thicknesses67comprising the same stent material(s)85. The four film thicknesses67are interconnected with three bonds65. The wall thicknesses13depicted inFIG. 76throughFIG. 78may be formed with one solid film66-A or two separate solid films66that comprise the same stent material(s)85. In other embodiments, the wall thickness13may comprise greater than four interconnected film thicknesses67comprising the same stent material(s)85. The wall thickness13of the stent10may include up to 2,000 film thicknesses67.

FIG. 79, depicts the wall thickness13of the linear ring struts20and the link struts21, wherein the wall thickness13comprises two film thicknesses67that comprise two different solid films66(solid film66-A and solid film66-B) that are made from two different stent material(s)85. Alternatively, the wall thickness13depicted inFIG. 79may comprise two interconnected film thicknesses67formed from two solid films66, wherein the solid films66are selected from any combination or permutation of solid film66-A, solid film66-B, solid film66-C or solid film66-D. Likewise, the arrangement of the solid films66may be reversed so that the solid film66-A is near located near the inner surface17and the solid film66-B is located near the outer surface16. The two different film thicknesses67are interconnected with one bond65.

FIG. 80, depicts the wall thickness13of the linear ring struts20and the link struts21, wherein the wall thickness13comprises three different film thicknesses67that comprise three different solid films66(solid film66-A, solid film66-B, solid film66-C) that are made from three different stent material(s)85. Alternatively, the solid films66may be chosen from any three of the following solid films66, wherein at least two or all the solid films66are different: solid film66-A, solid film66-B, solid film66-C, solid film66-D, solid film66-D and so on. The three different solid films66may also be arranged in a different order than what is depicted inFIG. 80. For example, wherein the solid film66order within the wall thickness66is inner surface17, middle, outer surface16, the solid films66may be arranged: F-A, F-B, F-C; F-B, F-A, F-C; F-B, F-C, F-A; F-C, FA, F-B; F-C, F-B, F-A; or F-A, F-C, F-B, wherein “F-A” refers to solid film66-A, “F-B” refers to solid film66-B, and “F-C” refers to solid film66-C. The three film thicknesses67are interconnected with two bonds65.FIG. 81, depicts the wall thickness13of the linear ring struts20and the link struts21, wherein the wall thickness13comprises four different film thicknesses67that comprise four different solid films66(solid film66-A, solid film66-B, solid film66-C, solid film66-D) that are made from four different stent material(s)85. The four film thicknesses67are interconnected with three bonds65. Although,FIG. 79throughFIG. 81depict the different solid films66arranged so that solid film66-A is positioned closest to the outer surface16, solid film66-B is positioned adjacent to solid film66-A on the side facing the inner surface17, solid film66-C is positioned adjacent to solid film66-B on the side facing the inner surface17and solid film66-D is positioned adjacent to solid film66-C on the side facing the inner surface17, in other embodiments the solid films66-A,66-B,66-C, and66-D may be arranged in any combination or permutation of these positions. In other embodiments the group of film thickness67depicted inFIG. 79thruFIG. 81may repeat within the stent10thickness13at least one additional time, wherein the word “group” refers to the combination or permutation of solid film66-A and solid film66-B, combination or permutation of solid film66-A, solid film66-B and solid film66-C, or combination or permutation of solid film66-A, solid film66-B, solid film66-C and solid film66-D. For example, in other embodiments, the wall thickness13depicted inFIG. 80could have six film thicknesses67, twelve film thicknesses67, fifteen film thicknesses67, eighteen film thicknesses67, twenty-one film thicknesses67, twenty-four film thicknesses67, twenty-seven film thicknesses67, thirty film thicknesses67, thirty-three film thicknesses67and so on, wherein the group or pattern of three film thicknesses67comprising the same or different stent material(s)85is repeated in the group of film thicknesses67that are added to underlying group of film thicknesses67within the stent10wall thickness13. The group or pattern of the film thicknesses67can be repeated as many times as necessary until the desired un-oriented42tube wall thickness45or oriented tube38wall thickness27is achieved so that the stent10can be formed having the wall thickness13within the specifications disclosed herein.

As previously disclosed, the number of different film thicknesses67within the wall thickness13is not limited to four different film thicknesses67. Therefore, in other embodiments there may be solid film66-E, solid film66-F, solid film66-G, solid film66-H, solid film66-I, solid film66-J and so on added to the group of film thicknesses67depicted inFIGS. 76-81. In other embodiments, there may be other patterns of film thicknesses67within the wall thickness13that are not depicted in the figures. For example, in an embodiment having a group comprising six film thicknesses67, there may be two solid films66-A, two solid films66-B and two solid film66-C to form at least three different layers51within the wall thickness13, wherein each layer51comprises two film thicknesses67or in another example embodiment there may be three solid films66-A and three solid film66-B to form at least two different layers51within the wall thickness13. In yet a few other example embodiments, there may be a group of four film thickness67wherein one solid film66comprises solid film66-A and three solid films comprise solid film66-B or wherein two solid films66comprise solid film66-A and two solid films comprise solid film66-B.

Although it is not depicted inFIG. 76thruFIG. 81, the stent wall thicknesses13formed of interconnected film thicknesses67may include the active ingredient(s)34located within at least one of the following positions: (1) within the film thickness67; (2) on at least one of the film major surface(s)73; (3) between at least two film thicknesses67; (4) on the stent10outer surface16; and/or (5) on the stent10inner surface17. Positioning the active ingredient(s)34on or between the inner surface17and the outer surface16of the wall thickness13of the stent10enables the stent10to have a sustained delivery of the active ingredient(s)34until at least the mass of the stent material(s)85within the implanted stent10are resorbed. Forming the wall thickness13from solid films66allows the time of the release of the active ingredient(s)34to be controlled and the delivered dosage of the active ingredient(s)34to be controlled in a way that minimizes or prevents restenosis and/or stent thrombosis at least until the mass of the stent10is resorbed. The timing of the release of the active ingredient(s)34from the implanted stent10may be controlled during the treatment provided by the implanted stent10by at least one of the following: (1) the selection of the stent material(s)85comprising each film thickness67, wherein the stent material(s)85having a faster degradation rate release the active ingredient(s)34in less time after deployment of the stent10than the stent material(s)85having a slower degradation rate; (2) the thickness of each film thickness67; wherein the thicker the solid film66the slower the release of all the active ingredient(s)34that are positioned within that film thickness67if the film thicknesses67comprise the same stent material(s)85; (3) the position of the active ingredient(s)34behind at least one barrier film thickness67; wherein the barrier film thickness67at least temporarily prevents the degradable elements within the contents6, local tissue and/or local cells that surround the implanted stent10from penetrating the therapeutic film thickness67that contains the active ingredient(s)34; (4) the selection of the morphology of the active ingredient(s)34and/or the stent material(s)85; wherein the more crystalline the active ingredient(s)34and/or the more crystalline the stent material(s)85the longer the duration of the drug therapy and the more amorphous the active ingredient(s)34and/or the more amorphous the stent material(s)85the shorter the duration of the drug therapy (5) the selection of the weight average molecular weight of the active ingredient(s)34and/or the stent material(s)85; wherein the higher the weight average molecular weight of the active ingredient(s)34and/or the higher the weight average molecular weight of the stent material(s)85the slower the release of the active ingredient(s)34from the stent10and the longer the duration of the drug therapy and the lower the weight average molecular weight of the active ingredient(s)34and/or the lower the weight average molecular weight the stent material(s)85the faster the release of the active ingredient(s)34from the stent10and the shorter the duration of the therapy.

The resorption rate of the stent material(s)85is a major factor that controls the rate at which the stent material(s)85are resorbed. The following resorption rates provide guidance on how the chemical composition of the solid film66will affect the time that the implanted stent10can provide radial support to the anatomical lumen36, the time that it takes to release the active ingredient(s)34and the time for the stent material(s)85within the stent10to be resorbed. The resorption rates provided in this guidance may be increased or decreased by at least one of the following: (1) co-polymerization of monomers; (2) blending of the stent material(s); (3) the stent10formation processes, which may increase or decrease the crystallinity of the stent material(s) and/or decrease the weight average molecular weight of the stent material(s); (4) inclusion of additives and/or active ingredient(s)34within the stent material(s)85; (5) the stent10geometry, (6) implantation site and/or position of the film thickness67within the stent wall thickness13. The following stent material(s)85have the approximate resorption times, wherein the “resorption time” means the time to complete the loss of stent material85mass after implantation of the stent10within the anatomical lumen36: (1) poly (L-lactide) has a resorption time of greater than 24 months; (2) poly (DL-lactide) has a resorption time of 12 to 16 months; (3) poly (glycolide) has a resorption time of 6 to 12 months; (4) poly (epsilon.caprolactone) has a resorption time of greater than 24 months; (5) copolymer of DL-lactide and glycolide having a 50/50 molar ratio has resorption time of 1 to 2 months; (6) copolymer of L-lactide and glycolide having an 85/15 molar ratio has a resorption time of 12 to 18 months; and (7) copolymer of L-lactide and epsilon.caprolactone having 70/30 molar ratio has a resorption time of 12 to 24 months. In other embodiments, the stent material(s)85may have approximate resorption times selected from the group: (1) copolymer of DL-lactide and glycolide having a 50/50 molar ratio and having an IV equal to about 0.2 dl/g or weight average molecular weight equal to about 17 kg/mol has resorption time of about 0.5 to 1 month or 0.75 to 1.5 months; (2) copolymer of DL-lactide and glycolide having a 50/50 molar ratio having an IV equal to about 0.4 dl/g and/or weight average molecular weight equal to 44 kg/mol has resorption time of about 0.75 to 1 month or about 1 to 2 months; (3) copolymer of DL-lactide and glycolide having a 50/50 molar ratio having an IV equal to about 1.0 dl/g and/or weight average molecular weight equal to 153 kg/mol has resorption time of about 3 to 4 months; (4) copolymer of DL-lactide and glycolide having a 75/25 molar ratio having an IV equal to about 0.2 dl/g and/or weight average molecular weight equal to 17 kg/mol has resorption time of about 2 to 3 months or about 3 to 4 months; (5) copolymer of DL-lactide and glycolide having a 75/25 molar ratio having an IV equal to about 0.7 dl/g and/or weight average molecular weight equal to 95 kg/mol has resorption time of about 4 to 5 months; (6) poly (DL-lactide) having an IV equal to about 0.2 dl/g and/or weight average molecular weight equal to 17 kg/mol has resorption time of about 6 to 9 months or 9-12 months; (7) poly (DL-lactide) having an IV equal to about 0.4 dl/g and/or weight average molecular weight equal to 45 kg/mol has resorption time of about 10 to 14 months; and/or (8) poly (DL-lactide) having an IV equal to about 0.5 dl/g and/or weight average molecular weight equal to 61 kg/mol has resorption time of about 12 to 16 months. It should be appreciated that stent material(s)85having resorption times between the examples provided herein may be formulated by varying the chemical composition (e.g. molar ratio of the monomers), blending the stent material(s)85to form a mixture and/or the varying the weight average molecular weight (Mw) of the stent material(s)85so that the resorption time of these variants fall within the ranges provided herein and that these variants are within the scope of the present invention.

Forming the wall thickness13from the solid films66creates a new mechanism for releasing the active ingredient(s)34into the area surrounding the stent's10implanted linear ring struts20and/or links struts21because as each active ingredient (34)-containing film thickness67erodes the stent10replenishes the anatomical lumen36with the active ingredient(s)34, which at least partially or completely mitigate the adverse reaction that may be the result of the stent material(s)85being resorbed. The new mechanism is superior to the drug delivery mechanism of the prior art that comprises a coating that is less than 0.005 mm thick comprising a mixture of a polymer and a drug that is adhered to the outer surface of the solid metallic or solid polymeric backbone of the stent because in the prior art mechanism the drug delivery starts immediately after implantation of the stent within the anatomical lumen, wherein 75% to 85% of the drug within the coating is released with 30 days of when the prior art stent is implanted within the anatomical lumen. This results in most of the prior art drug being vulnerable to being quickly washed away by the contents flowing through the prior art stent. The prior art bioresorbable stent provides virtually no drug delivery once the coating is removed from the prior art bioresorbable stent, which results in a long period of time wherein the material comprising the prior art stent is resorbing without any drug delivery to prevent late stent thrombosis. The prior art bioresorbable stent can be at least partially resorb within the anatomical lumen for 35 months without drug delivery. In contrast, in an embodiment of the stent10, the active ingredient(s)34are gradually released from the mass of the stent material(s)85that are positioned between the inner surface17and the outer surface16(“the backbone”) from the time the stent10is implanted within the anatomical lumen36, which results in the active ingredient(s)34being at least partially or completely retained within the proximity of the treatment site35so that they can prevent restenosis and/or late stent thrombosis from occurring until the mass of the stent material(s)85within the stent10backbone are resorbed.

In an embodiment, the amount of the active ingredient(s)34that are included within the stent10coating30may be within the range of: (1) greater than 0 to 25.mu.g/cm.sup.2 of treatment site35area; (2) greater than 0 to 50.mu.g/cm.sup.2 of treatment site35area; (3) greater than 0 to 75.mu.g/cm.sup.2 of treatment site35area; (4) greater than 0 to 100 .mu.g/cm.sup.2 of treatment site35area; (5) greater than 0 to 150.mu.g/cm.sup.2 of treatment site35area; (6) greater than 0 to 175.mu.g/cm.sup.2 of treatment site35area; (7) greater than 0 to 200.mu.g/cm.sup.2 of treatment site35area; (8) greater than 0 to 225 .mu.g/cm.sup.2 of treatment site35area; (9) greater than 0 to 250.mu.g/cm.sup.2 of treatment site35area; (10) greater than 0 to 275.mu.g/cm.sup.2 of treatment site35area; (11) greater than 0 to 300.mu.g/cm.sup.2 of treatment site35area; (12) greater than 0 to 325 .mu.g/cm.sup.2 of treatment site35area; (13) greater than 0 to 325.mu.g/cm.sup.2 of treatment site35area; (14) greater than 0 to 350.mu.g/cm.sup.2 of treatment site35area; or (15) greater than 0 to 400.mu.g/cm.sup.2 of treatment site35area, wherein the treatment site35area is calculated by the formula: Area equals 2.pi.rh, where r=the stent outer diameter11divided by two and h equals the stent length15. In other embodiments, the amount of the active ingredient(s)34that are included within the stent10coating30may be within the range of greater than 400.mu.g/cm.sup.2 to 5 g/cm.sup.2. The dosage of active ingredient(s)34depends on the application.

In an embodiment, the amount of the active ingredient(s)34that are included within the stent10may be within the range of: (1) greater than 0 to 25.mu.g/cm.sup.2 of treatment site35area; (2) greater than 0 to 50.mu.g/cm.sup.2 of treatment site35area; (3) greater than 0 to 75.mu.g/cm.sup.2 of treatment site35area; (4) greater than 0 to 100.mu.g/cm.sup.2 of treatment site35area; (5) greater than 0 to 150.mu.g/cm.sup.2 of treatment site35area; (6) greater than 0 to 175.mu.g/cm.sup.2 of treatment site35area; (7) greater than 0 to 200 .mu.g/cm.sup.2 of treatment site35area; (8) greater than 0 to 225.mu.g/cm.sup.2 of treatment site35area; (9) greater than 0 to 250.mu.g/cm.sup.2 of treatment site35area; (10) greater than 0 to 275.mu.g/cm.sup.2 of treatment site35area; (11) greater than 0 to 300 .mu.g/cm.sup.2 of treatment site35area; (12) greater than 0 to 325.mu.gAcm.sup.2 of treatment site35area; (13) greater than 0 to 325.mu.g/cm.sup.2 of treatment site35area; (14) greater than 0 to 350.mu.g/cm.sup.2 of treatment site35area; or (15) greater than 0 to 400.mu.g/cm.sup.2 of treatment site35area, wherein the treatment site35area is calculated by the formula: Area equals 2.pi.rh, where r=the stent outer diameter11divided by two and h equals the stent length15. In other embodiments, the amount of the active ingredient(s)34that are included within the stent10the stent10may be within the range of greater than 400 .mu.g/cm.sup.2. The dosage of active ingredient(s)34depends on the application.

The inclusion of the active ingredient(s)34within the stent wall thickness13may result in lowering the ductility of the wall thickness13. Reducing the ductility of the stent10wall thickness13can result in the stent10having low dilatation limits, which means that the stent10may become brittle and not be capable of having dilatation limits above 0.5 mm. The dilatation limits of the stent10including the active ingredient(s)34may be increased above 0.5 mm by including at least 0.01 wt. % of poly (epsilon.caprolactone) or a copolymer of epsilon.caprolactone in at least one of the solid films66containing the active ingredient(s)34that are used to form the stent10. The dilatation limits of the stent10including the active ingredient(s)34may be increased above 0.5 mm by including between greater than 0.0 wt. % to 25 wt. % of poly (epsilon.caprolactone) or a copolymer of epsilon.caprolactone and at least one other stent material(s)85in at least one of the solid films66used to form the stent10. Copolymers of (epsilon.caprolactone) and L-lactide, copolymers of (epsilon.caprolactone) and DL-lactide, blends of poly (epsilon.caprolactone) and poly (L-lactide) or blends of poly (epsilon.caprolactone) and poly (DL-lactide) are a few examples of useful stent material(s)85for increasing the stent's10ductility. In an embodiment, the poly (epsilon.caprolactone) may be included in at least one or all of therapeutic layers51. In another embodiment, the poly (epsilon.caprolactone) and/or copolymer of epsilon.caprolactone may be included in at least one or all of the barrier layers51. In yet one more embodiment, the poly (epsilon.caprolactone) and/or the copolymer of epsilon.caprolactone may be included in at least one or all of the barrier layers and at least one or all of the therapeutic layers51. In an embodiment, every other layer51, every third layer51every forth layer51or every fifth layer51may include at least one part poly (epsilon.caprolactone) or the copolymer of epsilon.caprolactone to increase the ductility of the stent10so that it does not fracture while being implanted in the anatomical lumen36.

The wall thickness13of the linear ring struts20and the link struts21depictedFIG. 82comprise two film thicknesses67that are interconnected by one bond65, wherein the active ingredient(s)34are positioned between the two film thicknesses67in the proximity of the bond65. The wall thickness13of the linear ring struts20and the link struts21depictedFIG. 83comprise three film thicknesses67that are interconnected by two bonds65, wherein the active ingredient(s)34are positioned between the three film thicknesses67in the proximity of the bonds65. The wall thickness13of the linear ring struts20and the link struts21depicted inFIG. 84comprise four film thicknesses67that are interconnected by three bonds65, wherein the active ingredient(s)34are positioned between the four film thicknesses67in the proximity of the bonds65.

The wall thickness13of the linear ring struts20and the link struts21depictedFIG. 85comprise two film thicknesses67that are interconnected by one bond65, wherein the active ingredient(s)34are positioned within the two film thicknesses67in the proximity of the middle of the film thicknesses67. The wall thickness13of the linear ring struts20and the link struts21depictedFIG. 86comprise three film thicknesses67that are interconnected by two bonds65, wherein the active ingredient(s)34are positioned within the three film thicknesses67in the proximity of the middle of the film thicknesses67. The wall thickness13of the linear ring struts20and the link struts21depictedFIG. 87comprise four film thicknesses67that are interconnected by three bonds65, wherein the active ingredient(s)34are positioned within the four film thicknesses67in the proximity of the middle of the film thicknesses67.

The wall thickness13of the linear ring struts20and the link struts21depictedFIG. 88comprises two film thicknesses67that are interconnected by one bond65, wherein the active ingredient(s)34are positioned within the two film thicknesses67in the proximity of the middle of the film thicknesses67and between the two film thicknesses67in the proximity of the bond65. The wall thickness13of the linear ring struts20and the link struts21depictedFIG. 89comprise three film thicknesses67that are interconnected by two bonds65, wherein the active ingredient(s)34are positioned within the three film thicknesses67in the proximity of the middle of the film thicknesses67and between the three film thicknesses67in the proximity of the bond65. The wall thickness13of the linear ring struts20and the link struts21depictedFIG. 90comprise four film thicknesses67that are interconnected by three bonds65, wherein the active ingredient(s)34are positioned within the four film thicknesses67in the proximity of the middle of the film thicknesses67and between the four film thicknesses67in the proximity of the bonds65.

The wall thickness13of the linear ring struts20and the link struts21depictedFIG. 91comprise two different film thicknesses67comprising two different solid films66(solid film66-A, solid film66-B) that are made from two different stent material(s)85that are interconnected by one bond65, wherein the active ingredient(s)34are positioned between the two film thicknesses67in the proximity of the bond65. The wall thickness13of the linear ring struts20and the link struts21depictedFIG. 92comprise three film thicknesses67comprising three different solid films66(solid film66-A, solid film66-B, solid film66-C) that are made from three different stent materials85that are interconnected by two bonds65, wherein the active ingredient(s)34are positioned within the three film thicknesses67. The wall thickness13of the linear ring struts20and the link struts21depictedFIG. 93comprise four film thicknesses67comprising four different solid films66(solid film66-A, solid film66-B, solid film66-C, solid film66-D) that are interconnected by three bonds65, wherein the active ingredient(s)34are positioned within the four film thicknesses67and between the four film thicknesses67in the proximity of the bonds65. AlthoughFIG. 78,FIG. 81,FIG. 84,FIG. 87,FIG. 90andFIG. 93depict four film thicknesses67within the linear strut20and link strut wall thicknesses13, in other embodiments, there may be greater than four film thicknesses within the wall thickness13. In other embodiments, the wall thickness13may include up to 2,000 interconnected film thicknesses67in the depicted configurations. AlthoughFIG. 82 through 93depict the active ingredient(s)34arranged in an orderly way, in other embodiments the active ingredient(s)34may be dispersed within the solid film66and/or between the solid films66in a disorderly way. In an embodiment, for example, when multiple, different solid films66are wrapped around the shaft74during formation of the un-oriented tube42and/or the oriented tube38, the group of multiple solid films66repeats within the wall thickness13as many times as the multiple, different solid films66were wrapped around the shaft74. AlthoughFIG. 92depicts that both solid film66-A and solid film66-B include the active ingredient(s)34, in other embodiments either solid film66-A or solid film66-B may be a barrier film66that excludes the active ingredient(s)34and the other solid film66may be the therapeutic solid film66that includes the active ingredient(s)34. Likewise, althoughFIG. 92andFIG. 93depict that solid film66-A, solid film66-B, solid film66-C and/or solid film66-D include the active ingredient(s)34positioned within all the solid films66and/or positioned between all the film thicknesses67, in other embodiments there may be at least one solid film66that is a barrier film66that excludes the active ingredient(s)34and at least one solid film66that is a therapeutic film66that includes the active ingredient(s)34. AlthoughFIG. 91throughFIG. 93always depict that solid film66-A is near the outer surface16, in other embodiment the solid film66-A and the other solid films66are arranged within the wall thickness13in any possible combination or permutation of the multiple solid films66.

FIG. 94, depicts the wall thickness13of the linear ring struts20and the link struts21in cross sectional view, wherein the wall thickness13comprises two layers51that are made from two different stent material(s)85. Layer51-A and layer51-B each comprise at least one film thickness67. At least one of the two-layers51may comprise up to 999 film thicknesses67that are interconnected by the bonds65. The two different layers51are interconnected with one bond65.FIG. 95, depicts the wall thickness13of the linear ring struts20and the link struts21in cross sectional view, wherein the wall thickness13comprises three different layers51that are made from three different stent material(s)85. Layer51-A, layer51-B and layer51-C each comprise at least one film thickness67. At least one of the three-layers51may comprise up to 998 film thicknesses67that are interconnected by the bonds65. The three layers51are interconnected with two bonds65.FIG. 96, depicts the wall thickness13of the linear ring struts20and the link struts21in cross sectional view, wherein the wall thickness13comprises four layers51that are made from four different stent material(s)85. Layer51-A, layer51-B, layer51-C and layer51-D each comprise at least one film thickness67. The layers51are interconnected with three bonds65. AlthoughFIG. 96depicts that the four layers51comprise four different stent material(s)85, the four-layer51embodiments may comprise only two different stent material(s)85because a layer51is formed when two immediately adjacent film thicknesses67comprising different stent material(s)85abut one another within the wall thickness13. Therefore, for example, layer51-A could be the same stent material85as layer51-C in FIG. C so long as layer51-B comprises a different stent material85than layer51-A and layer51-C or layer51-B could be the same stent material85as layer51-D so long as layer51-C comprises a different stent material85than layer51-B and layer51-D.

FIG. 97, depicts the wall thickness13of the linear ring struts20and the link struts21in cross sectional view, wherein the wall thickness13comprises the active ingredient(s)34positioned between two layers51that are made from two different stent material(s)85.FIG. 98, depicts the wall thickness13of the linear ring struts20and the link struts21in cross sectional view, wherein the wall thickness13comprises the active ingredient(s)34positioned within three layers51that are made from three different stent material(s)85.FIG. 99, depicts the wall thickness13of the linear ring struts20and the link struts21in cross sectional view, wherein the wall thickness13comprises the active ingredient(s)34positioned between the four layers51and within the four layers51that are made from four different stent material(s)85. AlthoughFIG. 97throughFIG. 99depict one row of the active ingredient(s)34within each layer51, it should be appreciated that each layer51may be comprised of multiple film thicknesses67, wherein the active ingredient(s)34are positioned within the film thicknesses67or between the film thicknesses67. Therefore, in another embodiment there may be multiple rows of the active ingredient(s)34within one or multiple layers51. Furthermore, in an embodiment of the wall thickness13at least one of the film thicknesses67within the layer(s)51is a therapeutic film thickness67that includes the active ingredient(s)34and at least one of the film thicknesses67within the layer(s)51is a barrier film thickness67that excludes the active ingredient(s)34. In yet one more embodiment, at least one of the layers51within the wall thickness13is a therapeutic layer51that includes the active ingredient(s)34and at least one of the layers51within the wall thickness13is a barrier layer51that excludes the active ingredient(s)34.

The layer(s)51comprises at least one and typically multiple film thicknesses67, which when the film thicknesses67are interconnected forms the layer thickness91.FIG. 100depicts a portion of the wall thickness13within the linear ring strut20or the link strut21. The portion of the wall thickness13depicted inFIG. 100depicts three discrete layers51-A,51-B and51-C, wherein the abluminal layer51(51-A) that is located near the outer surface16comprises five film thicknesses67, the luminal layer51(51-C) that is located near the inner surface17comprises seven film thicknesses67and the middle layer51(51-B) comprises six film thicknesses67. AlthoughFIG. 100depicts the wall thickness13comprising three layers106, there can be virtually any number of layers51within the wall thickness13, but generally not greater than 2,000 discrete layers51. Moreover, even thoughFIG. 100depicts there being five to7film thicknesses67within each layer51, the layer(s)51may comprise virtually any number of film thicknesses67within each discrete layer51, but generally not greater than 2,000 film thicknesses67within each discrete layer51. The luminal layer51located near the inner surface17may comprise more film thicknesses67than the middle layer(s)51and the middle layer(s)51may comprise more film thicknesses67than the abluminal layer51located near the outer surface16as depicted inFIG. 100, or the opposite. It is also possible that the middle layer(s)51comprise greater or lesser film thicknesses67than the abluminal layer51that is located near the outer surface16and/or the luminal layer51that is located near the inner surface17. It will be appreciated that even thoughFIG. 100depicts that the solid films66have the same thicknesses67within each of the layer(s)51, that the film thicknesses67may be different within each discrete layer51. The film thicknesses67and the layer thicknesses91may be the same or varied to control the delivery rate of the active ingredient(s)34after the stent10is implanted within the anatomical lumen36. The stent10wall thickness13comprising one solid film66that is formed into the roll52having multiple, immediately adjacent film thicknesses67comprising the same stent material85or the same blends of different stent material(s)85forms the stent10wall thickness13comprising one layer51having one layer thickness91like the embodiment depicted inFIG. 34. The stent10wall thickness13comprising at least two solid films66that are formed into the roll52having multiple, immediately adjacent film thicknesses67, wherein each of the solid films66comprise different stent materials85or different blends of stent materials85, forms the stent10wall thickness13comprising multiple layers51like the embodiments depicted inFIG. 36,FIG. 38,FIG. 40,FIG. 42andFIG. 44. For example, in an embodiment the solid film66-B comprising poly (L-lactide) is superimposed on top the solid film66-A comprising a copolymer of glycolide and L-lactide (at any molar ratio) as depicted inFIG. 35and arranged in the wall thickness57to form the roll52like depicted inFIG. 36comprising alternating layers51wherein the inner surface62comprises poly (L-lactide) and every other layer51is poly (L-lactide) separated by the copolymer of glycolide and L-lactide, and the outer surface61comprises the copolymer of glycolide and L-lactide, or the opposite. In yet one more embodiment of the two-solid film66roll52, the first solid film66-B comprises poly (L-lactide) having any weight average molecular weight described herein and the second solid film66-A comprises poly (DL-lactide) having any weight average molecular weight described herein, a copolymer of DL-lactide and L-lactide having any molar ratio described herein, a copolymer of caprolactone and L-lactide having any molar ratio described herein, a copolymer of DL-lactide and glycolide having any molar ratio described herein, poly (DL-lactide) having any weight average molecular weight described herein, poly (glycolide) having any weight average molecular weight described herein, poly (caprolactone) having any weight average molecular weight described here, copolymers L-lactide and DL-lactide having any molar ratio described herein, copolymers of L-lactide and glycolide at any molar ratio described herein, copolymers of L-lactide and caprolactone at any molar ratio described herein, or the opposite. In yet one more embodiment, the first solid film66-B comprises poly (L-lactide) having a weight average molecular weight between 1,014,000 g/mol and about 3,000,000 g/mol and the second solid film66-A comprises poly (L-lactide) having a weight average molecular weight between greater than 0 g/mol to 1,013,999 g/mol, or the opposite. The wall thickness13is formed of multiple layers51to control the degradation rate and/or resorption rate of the stent10or to control the delivery rate of the active ingredient(s)34.

FIG. 111depicts a table that includes example Stent Material Formulas275andFIG. 112depict a table that includes example Blend Formulas276. InFIG. 111the names of the stent material(s)85are abbreviated, wherein poly (L-lactide) is abbreviated a “PL,” poly (DL-lactide) is abbreviated as “PDL,” poly (glycolide) is abbreviated as “PG,” poly (D-lactide) is abbreviated “PD,” poly (.epsilon.caprolactone) is abbreviated as “PC,” the co-polymer of L-lactide and DL-lactide is abbreviated as “PLDL,” the copolymer of L-lactide and glycolide is abbreviated as “PLG,” the copolymer of L-lactide and .epsilon.caprolactone is abbreviated as “PLC,” the copolymer of DL-lactide and glycolide is abbreviated “PDLG,” and the copolymer of L-lactide and D-lactide is abbreviated “PLD.” In the tables depicted inFIG. 111andFIG. 112the terms “greater than” are abbreviated as “>” and the terms “less than” are abbreviated as “<.”

In an embodiment, the stent10comprises at least one “formula number”275and/or at least one “blend formula”276. For brevity “formula number1” may be abbreviated “F-1,” “formula number2” may be abbreviated “F-2,” “formula number3” may be abbreviated “F-3” and the remaining formula numbers may also be abbreviated using “F- and the next sequential number” until the last formula number80, which is abbreviated “F-80.” Likewise, “blend number”81may be abbreviated “B-81,” “blend number82” may be abbreviated “B-82,” “blend number83” may be abbreviated “B-83” and the remaining blend numbers may also be abbreviated using “B- and the next sequential number” until the last blend number180, which is abbreviated “B-180.” In an embodiment, the stent10is formed from the solid film66comprising at least one of the eighty “formula numbers” shown inFIG. 111(referred to as F-1to F-80) and/or at least one of the one hundred “blend numbers” shown inFIG. 112(referred to as B-81to B-180). In other embodiments, the stent10is formed from the other stent material(s)85or blends of the stent material(s)85provided within this specification.

FIG. 111depicts a table entitled “Example Stent Material85Formulations For Use In Producing The Film66” having nine columns, wherein: (1) column one is the formula number, (2) column two is the stent material85name, (3) column three provides the molar ratio of L-lactide in the polymer or copolymer, (4) column four provides the molar ratio of DL-lactide in the polymer or copolymer, (5) column five provides the molar ratio of D-lactide in the polymer or copolymer, (6) column six provides the molar ratio of glycolide in the polymer or copolymer, (7) column seven provides the molar ratio of caprolactone in the polymer or copolymer, (8) column eight provides the weight average molecular weight of the polymer or copolymer and (9) column nine provides the Inherent Viscosity of the polymer or copolymer. For example, Formula number1(“F-1”) comprises Poly (L-Lactide), which is a homopolymer of L-lactide that has a weight average molecular weight ranging from 55,000 g/mol to 3,000,000 g/mol and an Inherent Viscosity (“IV”) ranging from 0.7 to 11.0 dl/g. In another embodiment, Formula number41(“F-41”) comprises a copolymer of L-lactide and glycolide, wherein the molar ratio is 90 to less than 100 L-lactide and greater than 0 to 10 glycolide that has a molecular weight within the range of 55,000 g/mol to 3,000,000 g/mol and an IV within the range of 0.7 to 11.0 dl/g. The data provided for the other formula numbers shown in the other rows shown inFIG. 111may be interpreted the same way.

FIG. 112depicts a table entitled “Example Blend Formulations For Use In Producing Film66” that has four columns, wherein: (1) column one is the “blend number” (“B-81to B-180), (2) column two is the blend formulation that comprises blending or mixing at least two of the stent material85that are referred to by their formula number (e.g. F-1may be blended with F-19), (3) column three provides the weight percentage (wt. %) of the first stent material(s)85constituent within the blend (“Part A”), and (4) column four provides the weight percentage (wt. %) of the second stent material85constituent within the blend (“Part2”). For example, blend number81(“B-81”) comprises a mixture of formula number6(“F-6”) and at least one of the formulas numbers2,3,4and/or5(“F-2, F-3, F-4, F-5”), which means that blend81(“B-81”) may comprise at least one of fourteen combinations of stent material formulations275that are depicted inFIG. 111. In an embodiment, at least one of the solid films66is produced from a blend of at least one of the formulas275identified as F-1to F-80and at least one of the blends276identified as B-81to B-180.

Converting the stent material85constituents of the formulations275into the solution83makes the blends or mixtures. The solution83including the stent material formulations275and/or the blend formulations276is converted into the film66, the film(s)66are converted into the roll52or the Roll Including Active Ingredients143, the roll52or the Roll Including Active Ingredients143are converted into the un-oriented tube42or the oriented tube38and the un-oriented tube42or the oriented tube38are converted into the stent10as describe herein.

Industry sometimes describes the weight average molecular weight of a material in terms of “Inherent Viscosity.” One method of converting the weight average molecular weight into Inherent Viscosity or Inherent Viscosity into the weight average molecular weight is to use the Mark-Houwink equation as known by those skilled in the art. The Inherent Viscosity (“IV”) is determined by viscometry of diluted solutions. Measurements are performed in chloroform at a concentration of 0.1 g/dl. For low IV values higher concentrations are used: 2.0 g/dl for IV less than 0.2 dl/g; 1.0 g/dl for 0.2 dl/g less than or equal to IV less than 0.3 dl/g; 0.5 g/dl for 0.3 dl/g less than or equal to IV less than 1.0 dl/g. Gel Permeation Chromatography (GPC) determines the weight average molecular weight (Mw) in chloroform at 35.degrees. C relative to polystyrene (PS) standards. The Mark-Houwink equation gives the relation between the intrinsic viscosity ([n]) and viscosity average molecular weight (Mv), where [n]=K.(Mv)a. The constant “K” and “a” are the Mark-Houwink parameters. These are constant for fixed temperature, polymer type and solvent. Based on IV and GPC measurements the relationship between IV and Mw is determined. The data are fitted with the linearized form of the Mark-Houwink equation: ln(IV)=ln(K*)+a*.ln(Mw). The Mark-Houwink parameters are marked with an asterisk to emphasize the use of the inherent viscosity (IV) instead of the intrinsic viscosity ([n]), and the weight average molecular weight (Mw) instead of the viscosity average molecular weight (Mv). Examples of Mark-Houwink parameters are: for homopolymers of L-lactide are about K*=4.710-4 dl/g and a*=0.67, homopolymer of DL-lactide are about K*=1.810-4 dl/g and a*=0.72, copolymer of L-lactide and glycolide at a 85/15 molar ratio are about K*=3.3*10-4 dl/g and a*=0.67 and a copolymer of L-lactide and caprolactone at a 70/30 molar ratio are about K*=2.710-4 dl/g and a*=0.71. The present invention is not limited to material(s) having the Mark-Houwink parameters (K*, a*) or Inherent Viscosity (IV) and weight average molecular weight (Mw) correlations shown herein. Other parameters (K*, a*) for other Polymer(s) that are suitable for use in the present invention may be obtained by those skilled in the art of viscometry, GPC and the use of the Mark-Houwink equation.

In an embodiment, the stent10is formed from the roll52that is depicted inFIG. 36,FIG. 40,FIG. 42or the Roll Including The Active Ingredient(s)143that is depicted inFIG. 54,FIG. 60,FIG. 61wherein the solid film66-A and solid film66-B within the roll52comprise at least one of the eighty “formula numbers” shown inFIG. 111that are identified as F-1through F-80and/or comprise at least one of the one-hundred “blend formulas” shown inFIG. 112that are identified as B-81through B-180. In an embodiment, the solid film66-A comprises the same stent material formulation275or the same blend formulation276as solid film66-B. In another embodiment, the solid film66-A comprises a different stent material formulation275or a different blend formulation276than solid film66-B. In other embodiment(s) the stent10is formed from the roll52that is depicted inFIG. 36,FIG. 40,FIG. 42or the Roll Including The Active Ingredient(s)143that is depicted inFIG. 54,FIG. 60,FIG. 61wherein the solid film66-A and solid film66-B within the roll52at least partially or completely comprise at least one of the other stent material(s)85disclosed herein. The other stent material(s)85may also be used independently or when mixed together to form other blends or when mixed with the stent material formulations275and/or the blend materials276to form other blends. The stent10may also be formed from these other blends.

In an embodiment, the stent10is formed from the roll52that is depicted inFIG. 38orFIG. 44, and/or the Roll Including The Active Ingredient(s)143that is depicted inFIG. 56orFIG. 58wherein the solid film66-A, solid film66-B and solid film66-C within the roll52comprise at least one of the eighty “formula numbers” shown inFIG. 111that are identified as F-1through F-80and/or comprise at least one of the one-hundred “blend formulas” shown inFIG. 112that are identified as B-81through B-180. In an embodiment, the solid film66-A comprises the same stent material formulation275or the same blend formulation276as solid film66-B and solid film66-C. In another embodiment, at least one of the solid film(s)66comprises a different material formulation275or different blend formulation276as at least one or all of the additional solid films66within the roll52. In other embodiment(s) the stent10is formed from the roll52that is depicted inFIG. 38orFIG. 44or the Roll Including The Active Ingredient(s)143that is depicted inFIG. 56orFIG. 58, wherein the solid film66-A, solid film66-B and solid film66-C within the roll52at least partially or completely comprise at least one of the other stent material(s)85disclosed herein. The other stent material(s)85may also be used independently or when mixed together to form other blends or when mixed with the stent material formulations275and/or the blend materials276to form other blends. The stent10may also be formed from these other blends.

For simplicity, in the examples depicted inFIG. 33throughFIG. 67, the solid film66-A may be abbreviated “F-A,” solid film66-B may be abbreviated as “F-B,” solid film66-C may be abbreviated as “F-C” and so on. Likewise, the layer51-A may be abbreviated “L-A,” the layer51-B may be abbreviated “L-B,” the layer51-C may be abbreviated “L-C,” and so on. There may be greater than three solid films66included in the roll52and the Roll Including Active Ingredients143. These additional solid films66are not depicted in the figures because the features of the roll52and the feature of the Roll Including Active Ingredients143would not be clearly visible when additional solid films66are added to the figures. Therefore, it should be appreciated that in other embodiments, that there may be solid film66-D, solid film66-E, solid film66-F and so on sequentially until there are five hundred solid films66within the roll52or the Roll Including Active Ingredients143. When using the bijective base 26 numbering system, the five hundredth solid film66would be labeled solid film66-SF (abbreviated “F-SF”).

For example, in a three-film66embodiment, the roll52or the roll including active ingredients143may be configured in one of the following ways: (1) F-A, F-B and F-C all comprise the same stent material formulations275and/or blend formulations276; (2) F-B and F-C comprise the same stent material formulations275and/or blend formulations276and F-A comprises a different stent material formulation275and/or blend formulation276; (3) F-A and F-B comprise the same stent material formulations275and/or blend formulations276and F-C comprises a different stent material formulation275and/or blend formulation276; or (4) F-A and F-C comprise the same stent material formulations275and/or blend formulas276and solid F-B comprises a different stent material formulation275and/or blend formulation276. In a multi-film66embodiment wherein at least two of the solid films66comprise a different stent material formulation275and/or blend formulation276, the composition of the each of the different solid films66may be selected from any of the possible combinations or permutations of the stent material formulations275and/or the blend formulations276provided inFIG. 111andFIG. 112. In embodiments including greater than two different solid films, a person skilled in the art of statistics can calculate how many permutations and combinations are possible when selecting the composition of each of the solid films66within the roll52or the roll including active ingredients143, that are converted into the un-oriented tube42, which is converted into the oriented tube38and/or the stent10.

In the multi-film66embodiments, the films66are arranged in any order that provides the desired stent10degradation and/or resorption sequence while the stent10is implanted within the anatomical lumen36within the treatment site35. In an embodiment, the film thicknesses67and/or the layer thicknesses51are arranged within the stent wall thickness13so that the stent material(s)85comprising the stent wall thickness13erode starting from the outer surface16and ending at the inner surface16. In another embodiment, the film thicknesses67and/or the layer thicknesses51are arranged within the stent wall thickness13so that the stent material(s)85comprising the stent wall thickness13erode starting from the inner surface17and ending at the outer surface16. In one more embodiment, the film thicknesses67and/or the layer thicknesses51are arranged within the stent wall thickness13so that the stent material(s)85comprising the stent wall thickness13erode starting from between the inner surface17and the outer surface16(i.e. the middle of the stent wall thickness13) and ending at the outer surface16and/or the inner surface17, which results in the stent wall thickness13delaminating while the stent10is implanted within the anatomical lumen36. In another embodiment, the film thicknesses67and/or the layer thicknesses51are arranged within the stent wall thickness13so that the stent material(s)85comprising the stent wall thickness13erode first at the outer surface16, second at between the inner surface17and the outer surface16(i.e., the middle of the stent wall thickness13) and third at the inner surface17. In another embodiment, the film thicknesses67and/or the layer thicknesses51are arranged within the stent wall thickness13so that the stent material(s)85comprising the stent wall thickness13erode first at the inner surface17, second at between the inner surface17and the outer surface16(i.e., the middle of the stent wall thickness13) and third at the outer surface16. In another embodiment, the film thicknesses67and/or the layer thicknesses51are arranged within the stent wall thickness13so that the stent material(s)85erode layer-by-layer and/or film-by-film in any of the sequences described herein.

The capability of the stent10to erode layer-by-layer51and/or film-by-film66when it is implanted within the anatomical lumen36, provides the stent10with the capability to provide a sustained drug delivery (i.e. delivery of the active ingredient(s)34) during at least part or all of the duration that is takes for the mass of the stent material(s)85within the implanted stent10to be resorbed so that there is substantially no stent10mass left in the treatment area35. Moreover, the capability of the stent10to delaminate when it is implanted within the anatomical lumen36, provides the stent10with the capability to deliver the active ingredient(s)34to locations where the implanted ring struts20and link struts21contact the anatomical lumen36as well as to areas that are adjacent to where the cutting surfaces191of the linear ring struts20and link struts21contact the anatomical lumen36. In an embodiment, the stent10delivers the active ingredient(s)34to the portion of the anatomical lumen36that is in direct contact with the linear ring struts20and link struts21and/or to the region of the anatomical lumen36that is within 1 mm of all sides of where the liner ring struts20and the link struts21contact the anatomical lumen36, wherein the sides include at least one or all of: the outer surface16, inner surface17or the cutting surfaces191.

In an embodiment, after the stent10is implanted within the anatomical lumen36, at least one or all of the linear ring struts20and/or at least one or all of the link struts21are at least partially or completely covered with endothelial cells and/or partly or completely embedded within the thickness of the anatomical lumen36, so that the active ingredient(s)34that are positioned within the wall thickness13of the stent10are released in the area surrounding at least one or all of the linear ring struts20and/or at least one or all of the link struts21by at least one or all of the following mechanisms: (1) erosion of at least one film thickness67, wherein the active ingredient(s)34are located within at least one or all the film thicknesses67; (2) erosion of at least one of the film thicknesses67, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein all the film thicknesses67do not contain any active ingredient(s)34within the film thicknesses67; (3) erosion of at least one of the film thicknesses67, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein the outer film thickness67(closest to the abluminal surface) contains at least one active ingredient34and the inner film thickness67(closest to the luminal surface) does not contain any active ingredient(s)34; (4) erosion of at least one of the film thicknesses67, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein the outer film thickness67(closest to the abluminal surface) does not contain any active ingredient(s)34and the inner film thickness67(closest to the luminal surface) contains at least one active ingredient34; (5) erosion of at least one of the film thicknesses67, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein the outer film thickness67(closest to the abluminal surface) contains at least one active ingredient34and the inner film thickness67(closest to the luminal surface) contains at least one active ingredient34; (6) delamination of at least one of the film thicknesses67, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein all the film thicknesses do not contain any active ingredient(s)34within the film thicknesses67; (7) delamination of at least one of the film thicknesses67, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein the outer film thickness67(closest to the abluminal surface) contains at least one active ingredient34and the inner film thickness67(closest to the luminal surface) does not contain any active ingredient(s)34; (8) delamination of at least one of the film thicknesses67, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein the outer film thickness67(closest to the abluminal surface) does not contain any active ingredient(s)34and the inner film thickness67(closest to the luminal surface) contains at least one active ingredient34; (9) delamination of at least one of the film thicknesses67, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein the outer film thickness67(closest to the abluminal surface) contains at least one active ingredient34and the inner film thickness67(closest to the luminal surface) contains at least one active ingredient34; (10) diffusion of at least one active ingredient34, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein all the film thicknesses do not contain any active ingredient(s)34within the film thicknesses67; (11) diffusion of at least one active ingredient34, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein the outer film thickness67(closest to the abluminal surface) contains at least one active ingredient34and the inner film thickness67(closest to the luminal surface) does not contain any active ingredient(s)34; (12) diffusion of at least one active ingredient34, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein the outer film thickness67(closest to the abluminal surface) does not contain any active ingredient(s)34and the inner film thickness67(closest to the luminal surface) contains at least one active ingredient34; (13) diffusion of at least one active ingredient34, wherein the active ingredient(s)34are located between at least two film thicknesses67wherein the outer film thickness67(closest to the abluminal surface) contains at least one active ingredient34and the inner film thickness67(closest to the luminal surface) contains at least one active ingredient34; and/or (14) diffusion of at least one active ingredient(s)34, wherein the active ingredient(s)34are located within at least one or all the film thicknesses67.

In an embodiment, after the stent10is implanted within the anatomical lumen36, at least one or all of the linear ring struts20and/or at least one or all of the link struts21are at least partially covered with endothelial cells and/or partly or completely embedded within the thickness of the anatomical lumen36, so that the active ingredient(s)34that are positioned within the wall thickness13of the stent10are released in part or the complete area surrounding at least one or all of the linear ring struts20and/or at least one or all of the link struts21as the film thicknesses67erode. In an embodiment, after the stent10is implanted within the anatomical lumen36, at least one or all of the linear ring struts20and/or at least one or all of the link struts21are at least partially or completely covered with endothelial cells and/or partially or completely embedded within the thickness of the anatomical lumen36, so that the active ingredient(s)34that are positioned within the wall thickness13of the stent10are released in the area surrounding at least one or all of the linear ring struts20and/or at least one or all of the link struts21as the wall thickness13of the stent10delaminates. In an embodiment, after the stent10is implanted within the anatomical lumen36, at least one or all of the linear ring struts20and/or at least one or all of the link struts21are at least partially or completely covered with endothelial cells and/or partially or completely embedded within the thickness of the anatomical lumen36, so that the active ingredient(s)34that are positioned within the wall thickness13of the stent10are released in the area surrounding at least one or all of the linear ring struts20and/or at least one or all of the link struts21by diffusion, wherein diffusion is the result of the contents6or body fluids migrating into the wall thickness13of the stent10, partially or completely solubilizing and/or relocating at least part or all of the active ingredient(s)34so that at least part or all of the active ingredient(s)34that are within the stent10wall thickness13are released into the area surrounding the implanted linear ring struts20and link struts21.

In an embodiment the solid film66-A and solid film66-B are arranged in at least one of the following configurations: (1) solid film66-A (“F-A”) comprises slow rate degrading and/or resorbing stent material(s)85and solid film66-B (“F-B”) comprises medium rate degrading and/or resorbing stent material(s)85, (2) F-A comprises slow rate degrading and/or resorbing stent material(s)85and solid film66-B comprises fast rate degrading and/or resorbing stent material(s)85or (3) solid film66-A comprises medium rate degrading and/or resorbing stent material(s)85and solid film66-B comprises fast rate degrading and/or resorbing stent material(s)85, wherein the terms “slow rate” mean that the mass of the slow rate stent material(s)85are resorbed when the stent10is implanted in the anatomical lumen36in a longer time than “medium rate” and “fast rate” stent material(s)85, the terms “medium rate” mean the mass of the medium rate stent material(s)85are resorbed when the stent10is implanted in the anatomical lumen36in a longer time than the “fast rate” stent material(s)85and the terms “fast rate” mean that the mass of the fast rate stent material(s)85are resorbed when the stent10is implanted in the anatomical lumen36in a shorter time than the “medium rate” and “slow rate” stent material(s)85. In another embodiment the F-A and solid film F-B are arranged in at least one of the following configurations: (1) F-B comprises slow rate degrading and/or resorbing stent material(s)85and F-A comprises medium rate degrading and/or resorbing stent material(s) 85, (2) F-B comprises slow rate degrading and/or resorbing stent material(s)85and F-A comprises fast rate degrading and/or resorbing stent material(s)85or (3) F-B comprises medium rate degrading and/or resorbing stent material(s)85and F-A comprises fast rate degrading and/or resorbing stent material(s)85. Without intent on limiting, for example, the mass of the “fast rate” stent material(s)85may disappear from the treatment site35in less than 6 months after implantation of the stent10within the anatomical lumen36, the mass of the “medium rate” stent material(s)85may disappear from the treatment site35in less than 9 months after implantation of the stent10within the anatomical lumen36and the mass of the “slow rate” stent material(s)85may disappear from the treatment site35in less than 12 to 24 months after implantation of the stent10within the anatomical lumen36. In other embodiments, the “fast rate,” “medium rate” and “slow rate” stent material(s)85may disappear from the treatment site35in longer or shorter periods of time after implantation of the stent10within the anatomical lumen36.

Modifying the composition of the stent material formula275or the blend formula276influences the speed of degradation and/or resorption of the stent material(s)85when the stent10is implanted within the anatomical lumen36. For example, when the same stent material85has a lower weight average molecular weight it will degrade and/or resorb faster than when the stent material85has a higher weight average molecular weight. For example, F-6will degrade and/or resorb slower than F-5, F-5will degrade and/or resorb slower than F-4, F-4will degrade and/or resorb slower than F-3and F-3will degrade and/or resorb slower than F-2, when all other properties of the stent material85are the same. Alternatively, or additionally, modifying the chemical composition of the stent material formula275or the blend formula276, will influence the speed of degradation of the stent material(s)85. For example, polymers or copolymers that partially or completely comprise L-lactide, D-lactide or caprolactone will degrade and/or resorb slower than polymers or copolymers that partially or completely comprise DL-lactide and polymers or copolymers that partially or completely comprise DL-lactide will degrade and/or resorb slower than polymers or copolymers that partly or completely comprise glycolide.

Modifying, the crystallinity of the stent material(s)85will also influence the speed of degradation and/or resorption of the stent material(s)85when the stent10is implanted within the anatomical lumen36. For example, the same stent material85having a degree of crystallinity of 60% will degrade and/or resorb slower than the same stent material85having a degree of crystallinity of 50%, the same stent material85having a degree of crystallinity of 50% will degrade and/or resorb slower than the same stent material85having a degree of crystallinity of 40%, the same stent material85having a degree of crystallinity of 40% will degrade and/or resorb slower than the same stent material85having a degree of crystallinity of 30%, the same stent material85having a degree of crystallinity of 30% will degrade and/or resorb slower than the same stent material85having a degree of crystallinity of 20% and the same stent material85having a degree of crystallinity of 20% will degrade and/or resorb slower than the same stent material85having a degree of crystallinity of 10% because the molecules within the crystalline regions of the semicrystalline stent materials85are cleaved98slower than the amorphous regions. The more crystalline regions of the stent material(s)85are also slower to release the active ingredient(s)34than the more amorphous regions of the stent material(s)85within the implanted stent10by, for example, diffusion and/or erosion, because the crystalline regions are more ordered and the molecules within the crystalline region are more closely packed together, which makes it more difficult for body fluids within the treatment area35to penetrate the crystalline regions and initiate the degradation and/or resorption processes. By modifying these parameters as described herein, the degradation rate and/or the resorption rate of the stent10may be modified to achieve the optimum length of time that the stent10mechanically supports the anatomical lumen36for each treatment, the optimum drug delivery rate and duration of drug delivery during for each treatment, the optimum stent10decomposition mechanism for each treatment and the optimum time that the mass of the stent10is resorbed so that there is substantially no remaining stent material(s)85remaining within the treatment site35when there is no clinical need for the stent10to be implanted in the anatomical lumen36. Stent Material Formulas275and Blend Formulas276that are generally classified as fast rate degrading include at least one of the following: F-19, F-20, F-21, F-22, F-23, F-24, F-41, F-42, F-43, F-44, F-45, F-46, F-47, F-48, F-49, F-50, F-71, F-72, F-73, F-74, F-75, F-76, F-77, F-78, F-79, F-80, B-151, B-152, B-153, B-154, B-155, B-156, B-157, B-158, B-159, B-160, B-171, B-172, B-173, B-174, B-175, B-176, B-177, B178, B-179or B-180. Stent Material Formulas275and Blend Formulas276that are generally classified as medium rate degrading include at least one of the following: F-7, F-8, F-9, F-10, F-11, F-12, F-31, F-32, F-33, F-34, F-35, F-36, F-37, F-38, F-39, F-40, B-131, B-132, B-133, B-134, B-135, B-136, B-137, B-138, B-139or B-140. Stent Material Formulas275and Blend Formulas276that are generally classified as slow rate degrading include at least one of the following: F-1, F-2, F-3, F-4, F-5, F-6, F-13, F-14, F-15, F-16, F-17, F-18, F-25, F-26, F-27, F-28, F-29, F-30, F-51, F-52, F-53, F-54F-55, F-56, F-57, F-58, F-59, F-60, F-61, F-62, F-63, F-64, F-65, F-66, F-67, F-68, F-69, F-70, B-81, B-82, B-83, B-84, B-85, B-86, B-87, B-88, B-89, B-90, B-91, B-92, B-93, B-94, B-95, B-96, B-97, B-98, B-99, B-100, B-101, B-102, B-103, B-104, B-105, B-106, B-107, B-108, B-109, B110, B-111, B-112, B-113, B-114, B-115, B-116, B-117, B-118, B-119, B-120, B-121, B-122, B-123, B-124, B-125, B-126, B-127, B-128, B-129, B130, B-141, B-142, B-143, B-144, B-145, B-146, B-147, B-148, B-149, B-150, B-161, B-162, B-163, B-164, B-165, B-166, B-167, B-168or B-170.

Alternatively or additionally, inn an embodiment, the rolls52depicted inFIG. 38,FIG. 44and their variants, and the Rolls Including Active Ingredient(s)143depicted inFIG. 56,FIG. 58and their variants, are configured so that the solid films66have one of the following compositions: (1) F-A comprises a brittle stent material85, F-B comprises a ductile stent material85and F-C comprises a brittle stent material85; (2) F-A comprises a ductile stent material85, F-B comprises a brittle stent material85and F-C comprises a ductile stent material85; (3) F-A comprises a brittle stent material85, F-B comprises a brittle stent material85and F—C comprises a ductile stent material85; (4) F-A comprises a ductile stent material85, F-B comprises a brittle stent material85and F-C comprises a brittle stent material85; (5) F-A comprises a ductile stent material85, F-B comprises a ductile stent material85and F-C comprises a brittle stent material85; or (6) F-A comprises a brittle stent material85, F-B comprises a ductile stent material85and F-C comprises a ductile stent material85, wherein at brittle stent material85has an elongation-to-break equal to greater than 0% to 15% and the ductile stent material85has an elongation-to-break equal to equal to 15% to 100%.

FIG. 101depicts a Direct Roll Formation Process149. The Direct Roll Formation Process149is another method of producing the roll52, which is converted into the un-oriented tube42. As depicted inFIG. 101, the Direct Roll Formation Process149fundamentally comprises the shaft74that serves as the release media84, a head150, the liquid solution83, a Distance Between The Head And Shaft151, a Shaft Rotation Direction152, the liquid film87, the solid film66, a gaseous medium90, the Shaft Central Axis77, a Beginning Of The Application Area158, an End Of The Application Area159and a Drying Area160. The roll52and/or the Roll Including Active Ingredient(s)143, which are converted into the unoriented tube42, are formed directly on the shaft74by forming a plurality of liquid film thicknesses88that are converted into the solid film thicknesses67arranged in the configuration of the roll52on the shaft74. The shaft74is located adjacent to the head150. The shaft74rotates in the shaft rotation direction152. A Distance Between The Head And Shaft151separates the head150from the shaft74. In an embodiment, when the shaft74rotates in the opposite direction, the Beginning Of The Application Area158and End Of The Application Area159also have reversed positions. The head150applies the liquid solution83to the shaft74as the shaft74slowly rotates. Upon deposition the liquid solution83it coalesces on the shaft74forming the liquid film87on the shaft74outside of the drying area160. The shaft74rotates slowly so that the liquid film78is converted into the sufficiently dry solid film66within the gaseous environment90prior to application of another liquid film thickness88comprising. The gaseous environment90is located outside the shaft74during deposition. In an embodiment, there is at least one head150depositing liquid film thickness88so that the shaft74is covered for at least the length equal to the un-oriented tube length46. The deposited liquid film thickness88on the shaft74has at least one of the liquid film thicknesses88provided inFIG. 113. As the shaft74rotates around the shaft central axis77, the liquid film87is created between the Beginning Of Application Area158and the End Of Application Area159. As the shaft74rotates the liquid film87into the drying area160, the liquid film87is converted into a substantially dry solid film66by removing at least part of the solvent(s)86from the liquid film thickness88so that the solid film66includes substantially zero or insignificant bubbles and/or blisters. The solid film thicknesses67forms the un-oriented tube wall thickness45on the shaft74. When the liquid film87passes through the drying area160the liquid film thickness88is converted into the solid film thickness67that is much smaller than the liquid film thickness88. Once the shaft74completes a rotation around the shaft central axis77another liquid film thickness88is deposited over the previously deposited, substantially dry solid film66, which results in the second deposited film thickness67(“Over-Film Thickness93”) being adhered to first deposited film66(“Under-Film Thickness94”). The Direct Roll Formation Process149is repeated until the desired un-oriented wall thickness45that is capable of being formed into the oriented tube38and/or the stent10is achieved. Once the desired unoriented wall thickness45is achieved the un-oriented tube42that was formed on the shaft74is removed from the shaft74and converted into the oriented tube38and/or stent10.

The un-oriented tube42formed from the liquid solution83comprising the stent material85by the Indirect Roll Formation Process138or the Direct Roll Formation Process149may result in the formation of the un-oriented tube42that shrinks during heating and/or cooling. The unoriented tube42may shrink in length46by between 0% to 30% and until it snuggly fits the shaft outer diameter75when the un-oriented tube42is heated above the glass transition temperature of at least one or all the stent material(s)85comprising the un-oriented tube42and cooled below the glass transition temperature of at least one or all the stent material(s)85comprising the un-oriented tube42. It is believed that the unoriented tube42shrinks when heated and cooled because it undergoes a transition from a more amorphous to a more crystalline morphology. The un-oriented tube42is formed into the oriented tube38and/or the stent10.

In an embodiment, radially expanding and/or axially elongating the un-oriented tube42produces the oriented tube38. Orienting the molecular chains within the stent material(s)85that are within the un-oriented tube42by deforming the un-oriented tube42is believed to strengthen the un-oriented tube42. As depicted inFIG. 13, the oriented tube38has a larger nominal diameter and/or longer nominal length39than the un-oriented tube42, which is depicted inFIG. 12, as a result of the deformation process. Radially expanding and/or axially elongating the un-oriented tube42deforms the un-oriented tube42, which results in the oriented tube38becoming larger than the pre-cursor un-oriented tube42. In other embodiments, the un-oriented tube42is not deformed prior to converting the un-oriented tube42into the stent10and the stent10is formed from the un-oriented tube42.

A Mechanical Tube Orientation Process may be used to orient the stent material(s)85within the un-oriented tube42through deformation of the un-oriented tube42. The un-oriented tube42may be deformed by radially expanding and/or axially elongating the un-oriented tube42by passing the un-oriented tube42over a cylindrical-shaped shaft having a conical-shaped end. The cylindrical-shaped shaft having a conical-shaped end comprises a cylindrical-shaped shaft74and a cone on at least one end of the cylindrical-shaped haft having a conical-shaped end, wherein the small end of the cone is facing outward and the large end of the cone is facing toward and connected to the cylindrical-shaped shaft. The cone includes a taper so that the inner diameter43of the un-oriented tube42at least partially slides onto the cone and can transition to a larger outer diameter of the cylindrical-shaped shaft having conical-shaped end. In an embodiment the cone and/or the cylindrical-shaped shaft having a conical-shaped end are lubricated, covered with a lubricious coating, is polished or has a smooth surface to reduce drag as the unoriented tube42passes over the cylindrical-shaped shaft having a conical-shaped end. Alternatively, the cylindrical-shaped shaft having a conical-shaped end is not lubricated, coated, or smoothed. In an embodiment, drag exists when the un-oriented tube42passes over the cylindrical-shaped shaft having a conical-shaped end so that the un-oriented tube42is at least partially axially elongated as the un-oriented tube42passes over the cylindrical-shaped shaft having a conical-shaped End. The un-oriented tube42slides over the cylindrical-shaped shaft having a conical-shaped end in the direction of distal end26passing over the cone first and the proximal end25passing over the end of the cone second. The outer diameter of the cylindrical-shaped shaft having a conical-shaped end is substantially the same size as the outer diameter of the large end of the cone. The unoriented tube42has a starting inner diameter43that is smaller than the outer diameter of the cylindrical-shaped shaft having a conical-shaped end but large enough to slide over the small end of the cone. To achieve this the small end of the cone may be a sharp point or blunted point. In an embodiment, the un-oriented tube43is softened by heating the stent material(s)85within the un-oriented tube42to a temperature equal to or above the glass transition temperature of at least one or all the stent material(s)85comprising the un-oriented tube42. Alternatively, or additionally, the stent material(s)85comprising the un-oriented tube42are heated to a temperature below the glass transition temperature of at least one or all the stent material(s)85comprising the un-oriented tube42. The shaft74may be positioned within the Un-oriented Tube Passageway5during the softening process up until the time the un-oriented tube42passes from the shaft74onto the cone to prevent the unoriented tube42from becoming distorted or sagging during its softened state. The temperature of the cylindrical-shaped shaft having a conical shaped end and/or the gaseous environment90may be heated to a temperature greater than negative 100.degree. C to about the melting temperature of at least one of the stent material(s)85comprising the un-oriented tube42during the process; more narrowly within +/−50% of the glass transition temperature of at least one of the stent material(s)85comprising the un-oriented tube42during the mechanical tube orientation process. In other embodiments, the gaseous environment90is held at a higher or lower temperature. In the preferred embodiment, the gaseous environment90is a Protective Environment. Alternatively, the gaseous environment90is a liquid or protective liquid. In an embodiment, the entrance to the unoriented tube's42inner diameter43is positioned adjacent to the cone so that when the un-oriented tube42is pulled and/or pushed over the cone the un-oriented tube42slides over the cone in such a way that the inner diameter43of the un-oriented tube42increases in size as it is stretched over the cone. The cylindrical-shaped shaft having a conical-shaped end may be stationary or moving as the un-oriented tube42passes onto the cylindrical-shaped shaft having a conical-shaped end. Once the un-oriented tube42completely slides over the cone it slides onto a cylindrical portion of the cylindrical-shaped shaft having a conical end so that the inner diameter41of the oriented tube38substantially matches the size and shape of the cylindrical portion of the cylindrical-shaped shaft having a conical end. The inner diameter of the tube continues to increase until it reaches a fully expanded state wherein the oriented tube inner diameter41equals about the outer diameter of the cylindrical-shaped shaft having a conical end. The wall thickness45of the un-oriented42is drawn-down until it reaches the wall thickness27of the oriented tube38as depicted in the example provided inFIG. 100. As the un-oriented inner diameter43increases in size to the size of the oriented inner diameter41radial expansion of the un-oriented tube42occurs, which orients at least part or all the molecular chains within the stent material(s)85in the radial direction, which results in the oriented tube38having higher radial strength than the un-oriented tube42. Higher radial strength improves the capability of the stent10to hold open the anatomical lumen36after implantation. Alternatively, or additionally, the un-oriented tube42may be elongated as it is pulled and/or pushed over the cone and/or the cylindrical portion pf the cylindrical-shaped shaft having a conical end so that axial elongation occurs, which orients the at least part of the molecular chains within the stent material(s)85in the longitudinal direction, which results in the oriented tube38having higher tensile strength than the un-oriented tube42. Higher tensile strength prevents the stent10from fracturing when bending during deployment. As the un-oriented tube42passes over the cone, at least part of the molecular chains within the stent material(s)85within the oriented tube38orient in the direction of strain. After the unoriented tube42has passed over the cone and the oriented tube38is positioned so that it is in good fit and alignment with the cylindrical portion of the cylindrical-shaped shaft having a conical end, the oriented tube38and/or the cylindrical-shaped shaft having a conical shaped End are cooled to lock-in the molecular orientation and new dimensions of the oriented tube38. When the un-oriented tube42is converted into the oriented tube38, the volume of stent material(s)85flow into a new configuration, which results not only in an increase in diameter and/or length but also generally results in the wall thickness27of the oriented tube38being smaller than the wall thickness45of the unoriented tube42. The oriented tube38is removed from the cylindrical-shaped shaft having a conical-shaped end to be converted into the stent10as describe herein.

The rate of radial expansion and/or axial elongation can be influenced by the angle of the cone. A gradually increasing cone diameter will more slowly deform the diameter and/or length of the un-oriented tube42and a steep or abruptly increasing cone diameter will more quickly deform the diameter and/or length of the un-oriented tube42as the un-oriented tube42passes over the cone. In the preferred embodiment, the angle between the cylindrical-shaped shaft having conical end central axis and the cone outer surface ranges from greater than 0 degrees to about 80 degrees. In other embodiments, the angle is larger but up to no more than 90 degrees from the central axis of the shaft77. The speed at which the un-oriented tube42passes over the cone can range from greater than 0 mm/sec to about 10,000 cm/sec. In other embodiments, the speed is faster than 10,000 cm/sec but not faster than 900,000,000 m/sec.

Another method of converting the un-oriented tube42into the oriented tube38is a Stretch Blow Molding Process. The Stretch-Blow Molding Process may be used convert the roll52and/or the un-oriented tube42into the oriented tube38. The Stretch-Blow Molding Process fundamentally includes a parison, a parison closed end, a parison open end, a heater, a blow pin, a mold, a mold cavity, a gas and an elongation pin The parison is the un-oriented tube42including one closed end. The parison is softened by inserting the within the heater. The heater preferably softens the parison by heating the parison to a temperature that is above the glass transition temperature of at least one of the stent material(s)85comprising the parison, but no higher than 250 degrees Celsius. The softened parison is placed within the cavity of the mold and the two mold halves close. The cavity has the shape of a bottle. The elongation pin is inserted through the open end of the softened parison so that the elongation pin stretches the softened parison so that the length of the parison is increased. The elongation pin is withdrawn and the gas is forced through the open end of the parison through the blow pin so that the parison is inflated until the outer surface of the parison conforms to the mold cavity at which time the softened parison is cooled to a temperature that is at least below of the glass transition temperature of at least one of the stent material(s)85comprising the parison so that the parison retains the shape of the cavity and forms the bottle within the cavity. Cooling the expanded parison below the glass transition temperature is preferably performed within the range of greater than 0 degrees Celsius/minute to 500 degrees Celsius/nanosecond (“quenching”). Quenching may occur by, for example, by dipping the bottle in a cold liquid (below 40 degrees Celsius) or by exposing the part with liquid nitrogen. Typically cooling the parison occurs within the mold so that the bottle retains the shape of the cavity. Inflating the parison increases the smaller outer diameter44to the larger outer diameter40. The Stretch-Blow Molding Process produces the bottle. The bottle is removed from the mold by re-opening the mold halves. The bottle is removed from the mold and is converted into the oriented tube38by cutting a bottle top and a bottle bottom off the bottle. Alternatively, the stent10is formed from the bottle by cutting the strut pattern171directly into the bottle. The oriented tube38is the remaining portion of the bottle.

In embodiment, the stent materials(s)85are held at a temperature greater than the glass transition temperature of at least one of the stent material(s)85comprising the oriented tube38or bottle for a time within the range of greater than 0.0 seconds to about 30.0 minutes prior to cooling the oriented tube38or bottle to obtain the optimum crystallization of the oriented tube38. In other embodiments, the oriented tube38or the bottle is held at a temperature greater than the glass transition temperature of at least one of the stent material(s)85within the oriented tube38or bottle prior to cooling the oriented tube38or bottle on the cylindrical-shaped shaft having a conical end166or within the mold. The optimum residence time of the oriented tube38on the cylindrical-shaped shaft having conical end or bottle within the mold may be experimentally determined by conducting ladder experiments where the residence time and temperature are varied to determine the optimum conditions that produce the oriented tube38having the mechanical properties and degree of crystallinity required for the treatment to be provided by the stent10. In the preferred embodiment, the degree of crystallinity of the stent material(s)85within the stent10are within the range of greater than 0.0 percent to about 50 percent. In other embodiments, the degree of crystallinity of the stent material(s)85within the stent10are equal to or greater than 50 percent.

In an embodiment, the average degree of crystallinity of the stent material(s)85within the stent10is within the range of one of the following: (1) between 0% to 10% crystalline; (2) between greater than 0% to 10% crystalline; (3) between greater than 0% to 15% crystalline; (4) between greater than 0% to 20% crystalline; (5) between greater than 0% to 25% crystalline; (6) between greater than 0% to 30% crystalline; (7) between greater than 0% to 35% crystalline; (8) between greater than 0% to 40% crystalline; (9) between greater than 0% to 45% crystalline; (10) between greater than 0% to 50% crystalline; (11) between 5% to 10% crystalline; (12) between 10% to 15% crystalline; (13) between 15% to 20% crystalline; (14) between 20% to 25% crystalline or (15) between 25% to 30% crystalline. Differential Scanning calorimetry (“DSC”) may be used to determine the degree of crystallinity of the stent material(s)85within the Sent 10.

The roll52, the Roll Including the Active Ingredient(s)143and/or the un-oriented tube42may be radially expanded so that the Radial Expansion Ratio (“RER”) is within the range of greater than 0.0 to about 10.0. In other embodiments the RER is equal to or higher than 10.0. The RER means the nominal diameter of the oriented tube38(after expansion) divided by the smaller nominal diameter of the roll52or the un-oriented tube42(before expansion). Without intent on limiting, an un-oriented tube42having a starting nominal diameter equaling 0.5 millimeters, which is increased to be an oriented tube38having nominal diameter equaling 3.0 millimeters, would have an RER equal to 3.0 divided by 0.5, which means the RER equals 6.0.

Alternatively, or additionally, the roll52, the Roll Including Active Ingredient(s)143and/or the un-oriented tube42may be axially elongated so that the Axial Elongation Ratio (“AER”) is within the range of 0.0 to about 10.0. In other embodiments, the AER is equal to or greater than 10.0. The AER means the larger length39of the oriented tube38(after axial elongation) divided by the smaller length46of the un-oriented tube42(before axial elongation) or the larger length39of the oriented tube38(after axial elongation) divided by the smaller length58of the roll52(before axial elongation). Without intent on limiting, an un-oriented tube42having a starting length46equaling 14.4 millimeters, which is increased to be an oriented tube38having length39equaling 18.0 millimeters, would have a AER equal to 18.0 divided by 14.4, which means the RER equals 1.25.

Since the stent10experiences both radial and axial loads during use, in an embodiment, the oriented tube38comprising the stent10may be formed from the roll52, the Roll Including Active Ingredient(s)143and/or un-oriented tube42including both radial expansion and axial elongation. The Radial Expansion To Axial Elongation Ratio (“RETAER”) of the oriented tube38equals the RER divided by the AER. The RETAER quantifies the relative amount of radial deformation to axial deformation imparted on the roll52, Roll Including Active Ingredient(s)143and/or oriented tube38used to fabricate the stent10, where a RETAER equaling 1.0 means that the oriented tube38used to produce the stent10includes an equal amount of radial expansion and axial elongation. It is believed it is better to have greater molecular orientation in the radial direction than in the axial direction of the oriented tube38, so in the preferred embodiment the RETAER is within the range of greater than 1.0 to about 10.0. In other embodiments, the RETAER is equal to or greater than 10.0 or if there is no axial elongation imparted on the roll52and/or the un-oriented tube42the RETAER does not exist. Without intent on limiting, in the previous examples, RETAER is calculated by dividing 4.0 by 1.25, which means the RETAER is 3.2.

In an embodiment, the starting roll wall thickness54or the starting un-oriented tube42wall thickness45(before radial expansion/axial elongation) is thicker than the oriented tube's38ending wall thickness13(after radial expansion/axial elongation). In the preferred embodiment, the roll's51starting wall thickness57and/or the un-oriented tube's42starting wall thickness45may be larger than the oriented tube's38ending wall thickness27so that the wall thickness57,45may be drawn down from the larger wall thickness57,45to the smaller wall thickness27to increase the strength of the oriented tube38, which results in the stronger stent10. In other embodiments, the roll's52wall thickness57and/or the un-oriented tube's42starting wall thickness45is not made substantially larger than the oriented tube's38ending wall thickness13because the wall thickness may not need to be drawn down from a larger wall thickness57,45to a smaller wall thickness13to increase the strength of the stent10. It is believed that some Polymer(s) do not neck down when strained so that when these Polymer(s) are used, the roll wall thickness57and/or the unoriented tube wall thickness45may not need to be thicker than the oriented wall thickness13to achieve a strengthened oriented tube wall thickness27. The benefits of drawing down the wall thickness can be experimentally determined by drawing the stent material(s)85to ascertain if drawing down improves the mechanical properties of the stent material(s) 85. The Wall Thickness Draw Down Ratio (“WTDDR”) means the roll52starting wall thickness57divided by the oriented tube38wall thickness27or the un-oriented tube42starting wall thickness45divided by the oriented tube38ending wall thickness27. In the preferred embodiment, the WTDDR is within the range of greater than 0.0 and less than 10.0. In other embodiments, the WTDDR is equal to or greater than 10.0.

In the preferred embodiment, the stent material(s)85are fully comprised of one or more bioresorbable polymers, copolymers or combinations thereof. The stent material(s)85may have one chemical composition (“one material”) or multiple chemical compositions (“multiple materials”). The polymer(s) are either natural or synthetic. In other embodiments the stent material(s)85include other substances. In an embodiment, the bioresorbable polymer(s) are comprised of one or more molecule(s). The molecule(s) may be linear, branched or combination thereof. In the most preferred embodiment, the stent material(s)85within the stent10include at least one-part ultra-high weight average molecular weight (Mw) polymer(s) or copolymer(s), wherein the ultra-high weight average molecular weight (Mw) polymers have a weight-average molecular weight between greater than 621,000 g/mol to 3,000,000 g/mol, more narrowly greater than 1,014,000 g/mol to 3,000,000 g/mol.

In an embodiment, the post-processed stent material(s)85within the stent10include less than 0.01 percent residual solvent(s)86. In other embodiments, the post-processed material(s)85within the stent10include equal to or greater than 0.01 percent residual solvent as determined by gas chromatography (“GC”). In an embodiment, the post-processed stent material(s)85within the stent10include less than 0.01 percent residual monomer as determined by GC. In other embodiments, the post-processed material(s)85within the stent10include equal to or greater than 0.01 percent residual monomer as determined by GC. In an embodiment, the post-processed stent material(s)85within the stent10include less than 0.5 percent water as determined by coulometric titration. In other embodiments, the postprocessed material(s)85within the stent10include equal to or greater than 0.5 percent residual water as determined by coulometric titration. In the preferred embodiment, the post-processed stent material(s)85within the stent10include less than 50 ppm residual tin content as determined by atomic absorption spectroscopy. In other embodiments, the post-processed material(s)85within the stent10include equal to or greater than 50 ppm tin content.

In an embodiment, the stent10comprises at least one part or completely comprises post-processed, ultra-high weight average molecular weight (Mw) poly (L-lactide), which has a post-processed weight average molecular weight (Mw) equal to or greater than 110,000 grams per mole (g/mol), more preferably equal to or greater than 130,000 grams per mol (g/mol), even more preferably equal to or greater than 300,000 grams per mole (g/mol), yet more preferably equal to or greater than 725,000 grams per mole (g/mol), still even more preferably equal to or greater than 1,000,000 grams per mole (g/mol) and most preferably equal to or greater than 1,300,000 grams per mole (g/mol) using Gel Permeation Chromatography (GPC) performed in chloroform at 35.degree. C relative to polystyrene (PS) as standards. In other embodiments, the stent10comprises at least one part or completely comprises post-processed poly (L-lactide), which has a weight average molecular weight (Mw) after processing that is less than 100,000 grams per mole (g/mol) or above 1,300,000 grams per mole (g/mol). It should be appreciated that the weight average molecular weight (Mw) of the Polymer(s) can be determined by other methods know by those skilled in the art and that the molecular weight measurements are not limited to measuring using Gel Permeation Chromatography (GPC) performed in chloroform at 35.degree. C relative to polystyrene (PS) as standards.

In an embodiment, at least one film thickness67comprising the ultra-high weight average molecular weight material(s)85is positioned on the inner surface17of the stent10. In an embodiment, at least one film thickness67comprising the ultra-high weight average molecular weight material(s)85is positioned on the outer surface16of the stent10. In an embodiment, at least one film thickness67comprising the ultra-high weight average molecular weight material(s)85is positioned on the inner surface17and the outer surface of the stent10. It is believed that the ultra-high weight average molecular weight (Mw) material(s) 85 degrade more slowly than medium or low weight average molecular weight stent material(s)85, which helps maintain the stent's10radial strength during the initial part of the time that the stent10is implanted within the anatomical lumen36. In an embodiment, the stent10maintains at least 85% to 100% of its initial radial strength for a duration selected from the group of: (1) greater than 0 minutes to 1 day; (2) greater than 1 day to 1 week, (3) greater than 1 week to 1 month, (4) greater than 1 month to 45 days, (5) greater than 45 days to 2 months, (6) greater than 2 months to 3 months, (7) greater than 3 months to 4 months, (8) greater than 4 months to 5 months, (9) greater than 5 months to 6 months, (10) greater than 6 months to 7 months, (11) greater than 7 months to 8 months, (12) greater than 8 months to 9 months, (13) greater than 9 months to 10 months, (14) greater than 10 months to 11 months or greater than 11 months to 12 months, wherein the duration starts when the stent10is implanted within the anatomical lumen36. In an embodiment, the stent10maintains at least 60% to 100% of its initial radial strength for a duration selected from the group of: (1) greater than 0 minutes to 1 day; (2) greater than 1 day to 1 week, (3) greater than 1 week to 1 month, (4) greater than 1 month to 45 days, (5) greater than 45 days to 2 months, (6) greater than 2 months to 3 months, (7) greater than 3 months to 4 months, (8) greater than 4 months to 5 months, (9) greater than 5 months to 6 months, (10) greater than 6 months to 7 months, (11) greater than 7 months to 8 months, (12) greater than 8 months to 9 months, (13) greater than 9 months to 10 months, (14) greater than 10 months to 11 months or greater than 11 months to 48 months, wherein the duration starts when the stent10is implanted within the anatomical lumen36. In other embodiments, the stent10maintains equal to or less than 60 percent of its initial radial strength for the same durations. In an embodiment, the stent10has an initial radial strength equal to 100 mmHg (0.013 MPa) to 2000 mmHg (0.27 MPa), wherein the initial radial strength is the radial strength at the time the stent10is implanted within the anatomical lumen36. In other embodiments, the stent10has an initial radial strength equal to or lower than 100 mmHg or higher than 2000 mmHg.

A polydispersity index (“PDI” or “Dispersity”), which is calculated by dividing the weight-average molecular weight (Mw) by the number-average molecular weight (Mn), is a suitable method for determining the molecular weight distribution of the post-processed stent material(s)85. A monodisperse stent material85has a PDI equal to 1.0. A PDI that is in the range of greater than 1.0 to about 1.1 is generally considered to be a narrow molecular weight distribution. A PDI that is in the range of equal to or greater than 1.1 to about 2.0 is a moderate molecular weight distribution. A PDI that is in the range of equal to or greater than 2.0 is a broad molecular weight distribution. The stent10may be comprised of raw stent material(s)85or post-processed stent material(s)85having a narrow, moderate or broad molecular weight distribution. Therefore, in an embodiment the stent10is comprised of polydisperse raw stent material(s)85or post-processed stent material(s)85having a PDI that is greater than 1. In an embodiment, the stent10comprises post-processed stent material(s)85comprising a broad molecular weight distribution having a PDI within the range of about 2.5 to 5.0, which is believed to produce a stronger stent10.

The stent10may be comprised of an amorphous polymer. The stent10may be comprised of a crystalline polymer. The stent10is preferably comprised of a semi-crystalline polymer. The wall thickness13of the stent10may include at least one layer51of semi-crystalline stent material(s)85and at least one layer of amorphous stent material(s)85, wherein the semi-crystalline layer51provides temporary support to the anatomical lumen36or a temporary barrier to the release of the active ingredient(s)34and the amorphous layer51provides storage for the active ingredient(s)34and release of the active ingredient(s)34. It is also possible that the layer51closest to the inner surface17(luminal surface) has a higher degree of crystallinity than the layer51or layers51that are near the outer surface16(abluminal surface) so that the luminal layer51maintains radial strength longer and/or resorbs slower than the abluminal layer(s)51. The more crystalline luminal layer51may be formed by forming the first roll52of interconnected film thicknesses67on the shaft74and heating and cooling the luminal layer51until the crystallinity of the luminal layer51increased and then attaching additional film thicknesses67to the more crystalline layer51that are more amorphous or less crystalline. The semi-crystalline polymer includes a lamellae. The stent10may include at least one spherulite. The spherulites include a nuclei, the lamellae and a tie chain molecules, which interconnect the lamella. It is preferred that the spherulites be smaller than 0.010 mm, more narrowly less than 0.005 mm, in size.

In an embodiment, the stent10can be radially expanded during deployment so that the stent's deployed diameter is greater than 0.5 millimeters (mm) larger than the stent's10nominal diameter, more preferably more than twenty (20) percent (%) larger than the stent's10nominal diameter, more preferably greater than forty-five (45) percent (%) larger than the stent's10nominal diameter, without fracturing and still being able to support the anatomical lumen36during the treatment time. In other words, the stent's10maximum post-dilatation diameter is preferably greater than 0.5 millimeters larger than the stent's10nominal diameter, more preferably greater than 20% larger than the stent's10nominal diameter, and most preferably greater than 45% larger than the stent's10nominal diameter, wherein the nominal diameter equals the nominal diameter of the un-oriented tube42or oriented tube38at the time the strut pattern171is cut into the un-oriented tube42or oriented tube38plus the thickness of the coating30(if present).

The stent material(s)85comprising the stent10may be adapted to include at least one reinforcement to form a composite material. The reinforcement(s) may have any shape. For example, the reinforcement may have a substantially spherical shape, an ovoid or egg shape, a rod shape, a flake shape or other structural shapes. The reinforcement includes a reinforcement outer surface. The reinforcement may include at least one undercut that may manifest itself as a texture, protrusion, indentation or fissure within the reinforcement's outer surface. The configuration of the reinforcement's outer surface(s) or a coating on the outer surface(s) may improve the strength of the bond between the stent material(s)85and the reinforcements.

In an embodiment, the stent10may be comprised of the composite material, wherein the composite matrix is formed of the reinforcements(s) that are at least partially or completely separated by the stent material(s)85. The composite matrix within the composite material separates the reinforcement(s) by a Y-axis separation distance, a Z-axis separation distance and an X-axis separation distance. In an embodiment, the reinforcement(s) may comprise at least one active ingredient(s)34. In an embodiment, the reinforcement(s) comprise at least one chemical metal element or alloy comprising multiple chemical metal elements. The alloy may include HRE and/or RE. The reinforcement may include a passivation layer. In an embodiment, the Y-axis separation distance ranges from 0.000 mm to 0.085 mm and the Z-axis separation distance and the X-axis separation distance range in size from about 0.00 mm to 0.150 mm, wherein the Y-axis separation distance is the position of the reinforcement within the wall thickness13, Z-axis separation distance is the position of the reinforcement within the diameter and X-axis separation distance is the position of the reinforcement within the length15.

FIG. 102depicts an ultra-high molecular weight stent material96andFIG. 105depicts a low molecular weight stent material97. In an embodiment, the stent material85comprises at least one part made from an ultra-high molecular weight material96. As depicted inFIG. 131, a long molecular chain characterizes the ultra-high molecular weight material96. Forming the stent10from at least one ultra-high molecular weight stent material96increases the radial strength of the stent10, increases the elongation-to-break of the stent10so that the stent10may have larger dilatation limits, makes at least one part of the stent10degrade and/or resorb more slowly, releases the active ingredient(s)34more slowly, and/or makes a longer lasting barrier layer51that delays or slows down the release of the active ingredient(s)34positioned within a therapeutic layer51and/or film thickness67. Forming one part of the stent10from at least ultra-high molecular weight stent material96and another part with at least one part with a lower molecular weight stent material134is a critical element of making the controlled drug delivery stent10having sustained drug delivery when using the stent material formulations275and blend formulations276provided inFIG. 111andFIG. 112.

During formation of the ultra-high molecular weight stent material96into the stent10, the long chain is cleaved98at random locations along the chain as depicted inFIG. 103. The term “cleaved” may also be referred to as scission. The cleaving of the chain results in dividing the long chain into shorter chains of varying lengths as depicted inFIG. 104, which results in the stent10comprising post-processed stent materials99that have shorter chains. Cleaving of the ultra-high molecular weight stent material96may also reduce the mechanical properties of the stent10, wherein, for example, the radial strength and/or elongation-to-break properties are reduced. Converting the ultra-high molecular weight stent material96into at least part of the stent10using the stent10formation methods described herein reduces the negative impact of converting the ultra-high molecular weight stent material96into the stent10because the ultra-high molecular weight stent material96is not exposed to high shear stresses, high temperatures and the formation methods preferably occurs within a Protective Environment. Converting the ultra-high molecular weight stent material96into at least part of the stent10using the methods described herein may reduce the reduction in the weight average molecular weight of the stent material(s)85within the stent10. However, using the methods of producing the stent10described herein may reduce the weight average molecular weight of the stent material(s)85within the stent10during formation of the stent10so that the pre-processed (“raw”) stent material(s)85have a weight average molecular weight (Mw) that is reduced to a post-processed stent material(s)85weight average molecular weight (Mw).

In the prior art, bioresorbable stents are comprised of the low molecular weight material97as depicted inFIG. 105. Like the ultra-high molecular weight material96, during the conversion of the low molecular weight material97into a prior art stent the low molecular weight material97is also cleaved98into shorter chains at random locations along the chain a depicted inFIG. 106. However, after cleavage, the low molecular weight material97results in very low post-processed molecular weight polymers99having significantly shorter chains as depicted inFIG. 107. In an embodiment, the present invention forms the stent10from stent materials85at least partially comprising the ultra-high molecular weight material96because starting the formation of the stent10from the longer ultra-high molecular weight material chains96results in a much stronger stent10having superior crack resistance than when the stent10is formed of the low molecular weight material97, which is prone to cracking.

The un-oriented tube42may not be concentric or it may include irregularities on the outer surface47. The Plate Rounding Fixture266, depicted inFIG. 110, and/or the Roller Rounding Fixture267, depicted inFIG. 109, may be used to improve the concentricity and/or surface47of the un-oriented tube43prior to converting the un-oriented tube42into the stent10or the oriented tube38. It is desirable for the un-oriented tube42to be concentric when cutting a high precision strut pattern into the tube wall thickness. As depicted inFIG. 110, the Plate Rounding Fixture266method comprises a flat surface264, a spacer265, the shaft74and the un-oriented tube42. The concentricity and surface of the un-oriented tube42may be improved by the following method: (1) placing the spacers265having a thickness equal to the final un-oriented tube42wall thickness45on the flat surface264; (2) positioning the un-oriented tube74on the shaft74outer surface78; (3) softening the stent material(s)85comprising the un-oriented tube42by heating the un-oriented tube42on the shaft74; (4) rolling the heated un-oriented tube74over the flat surface264while keeping the shaft74outer surface78in contact with the spacers265and (5) cooling the un-oriented tube42after the softened un-oriented tube42has rolled over the flat surface264at least on complete revolution.

As depicted inFIG. 109, the Roller Rounding Fixture267method comprises a cylindrical-shaped roller268, the shaft74and the unoriented tube42. The concentricity and surface of the un-oriented tube42may be improved by the following the method: (1) positioning the unoriented tube74on the shaft74outer surface78; (3) softening the stent material(s)85comprising the un-oriented tube42by heating the unoriented tube42on the shaft74; (4) spinning the un-oriented tube42on the shaft74clockwise and spinning the shaping roller268counter clockwise (or the opposite directions) so that the un-oriented tube42wall thickness45is set by the distance between the shaft central axis77and the shaping roller central axis269and (5) cooling the un-oriented tube42after the complete outer circumference of softened un-oriented tube42has passed between the shaping roller268and the shaft74at least one time.

The stent10includes a strut pattern171. The strut pattern171, which is depicted in flat planar view inFIG. 114, is cut into the oriented tube's38wall thickness27or the un-oriented tube's42wall thickness45. The strut pattern171forms a tubular shape surrounding the stent central axis14when a Strut Pattern Bottom Edge187and a Strut Pattern Top Edge188(19 shown) are connected in a tubular configuration. The strut pattern171fundamentally includes a crest189and a trough190, which forms the approximately sinusoidal-shaped ring19that is connected to other rings19with the link struts21. A cutting surface191forms the boundary around the rings19and the link struts21that forms the cell22within the un-oriented tube42or the oriented tube38. The cell22is an empty space within the wall thickness27of the oriented tube38or wall thickness45of the un-oriented tube42the stent material(s)85have been removed during the strut pattern171cutting process. The linear ring struts20and the link struts21partially or completely surround the cell22.FIG. 114depicts eight linear ring struts20and two link struts21completely surrounding the cell22. At the junction of each linear ring strut21and/or link strut21there is a curved hinge element281. Five of the curved hinge elements281have been circled with a dashed line so that the curved hinge elements281can be identified. In other embodiments, there may be more or less ring struts20and link struts21surrounding the cell22. One of the cells22is shown hatched and one of the cutting surfaces191is shown in a bold line inFIG. 114for easy visualization. The strut pattern171may also include a at least one marker strut192, which contains a radiopaque material to assist with visualization of the proximal end25and distal end26of the stent10during delivery and implantation of the stent10within the anatomical lumen36. Alternatively, the linear ring strut20and the link strut21may at least partially comprise a mixture of a radiopaque material and the stent material(s)85that enable the entire stent10to be visualized during delivery of the stent10to the treatment site35. The radiopaque material may be in the range of greater than 0.000 mm to 0.001 mm, preferably nano size. Platinum powder may, for example, provide visualization of the stent10during delivery and may be bioresorbable as the body of the implanted stent10loses mass. The linear ring strut20has a linear strut width279and the link strut has a link strut width280.

A pattern of rings19and link struts21may be formed within the un-oriented tube42or the oriented tube38by removing portions of the un-oriented wall thickness45or the oriented wall thickness13by chemical etching, mechanical cutting, or laser cutting materials away from within the wall thickness45of the un-oriented tube42and/or the wall thickness13of the oriented tube38. Without limitation, the strut pattern192may be cut into the un-oriented wall thickness45or oriented wall thickness13with an ultra-short-pulse laser having pulse with duration shorter than about a picosecond (=10-12), an ultra-short-pulse laser having a pulse duration shorter than about a femtosecond (=10-13 or in some cases 10-15), or a long pulse laser having a pulse duration of about a nanosecond (=10-9). Suitable lasers are available from Rofin-Baasel Laser GmbH, Petersbrunner Str., Starnberg, Germany (now called Coherent Munich GmbH & Co. KG, ZeppelinstraRe 10-12, 82205 Gilching, Germany).

FIG. 115depicts an Exploded Tube271from the end view of an un-oriented tube42or oriented tube38that was formed from one solid film66. As previously disclosed, in other embodiments there may be multiple solid films66. The Exploded Tube270depicts the film thicknesses67separated within the un-oriented tube42wall thickness45or the oriented tube38wall thickness27so that the spiral configuration of the solid film66can be easily visualized. In an embodiment, the adjacent film thicknesses67are interconnected and there is no gas or empty space within the separation distance60between the film thicknesses67. However, in another embodiment there may be active ingredient(s)34positioned within the separation distance60, wherein the areas surrounding the active ingredient(s)34are substantially filled with the stent material(s)85. In yet one more embodiment, there may be at least one part void space127within the wall thickness13. Generally, the void space127is less than 10 vol. % of the wall thickness13. In other embodiments, the void space127may be equal to or greater than 10 vol. %.

FIG. 115depicts a retained portion272that is adjacent to two removed portions273of the wall thickness, which are created when the strut pattern171is cut into the un-oriented tube wall thickness45or the oriented wall thickness27. The cutting lines278show the approximate pathway of where at least one part of where the cutting device travels when cutting out the removed portions273from the un-oriented tube42or the oriented tube38. The cutting lines278are shown as dashed lines inFIG. 115. The retained portion272becomes the linear ring strut20or the link strut21. The removed portion272becomes waste that may be disposed of or recycled.FIG. 115depicts fourteen cutting surfaces191, which would result in the production of seven equally spaced struts surrounding the central axis14of the stent10if the tube is cut at each of the fourteen cutting surfaces191. One of the linear ring struts20or link struts21is shown in the balloon274so that it is easy to visualize how the linear ring struts20and link struts21are formed of the interconnected film thicknesses67and/or layers51. It should be appreciated that the cutting lines278and the balloon274are not part of the stent10.

The stent10, the un-oriented tube42, the oriented tube38, the film66, the fiber116, the multi-fiber117, the fibrous sheet108, the laminate100, the infused fibrous sheet126, the roll52, the Roll Including Active Ingredient(s)143, the infused fiber-reinforced laminate130, the reinforcement(s), the active ingredient(s)34and/or combinations thereof may be formed or processed under a protective environment. To at least partially preserve the degree of polymerization of the stent material(s)85, at least partially preserve the molecular weight of the stent material(s)85or the stability of the reinforcement(s) during processing, the stent10may be formed within a protective environment (herein referred to as “Protective Environment”). Without limitation, the mixing, dissolving, storing, film forming, fiber forming, roll forming, heating, liquefying, casting, cooling, infusing, assembling, laminating, solidifying, fusing, sintering, crystallizing, strut pattern cutting, surface modification, coating, transferring, crimping, packaging, sterilizing or combinations thereof processes may be performed within the Protective Environment. The Protective Environment, for example, minimizes or prevents degradation of the stent material(s)85or active ingredient(s)34efficacy due to thermal processing, hydrolysis, or shear stresses; minimizes or prevents oxidation of the reinforcement(s); minimizes or prevents fires; minimizes or prevents reactivity of the reinforcement(s) with ambient air or moisture; minimizes or prevents the degradation of the active ingredient(s)34, or combinations thereof. The Protective Environment may be, for example, partially or fully comprise an inert atmosphere, noble gases (i.e., helium, neon, argon, krypton, xenon, and radon), nitrogen, dried air (e.g., air including humidity below 20%), moisture-free air, low oxygen containing or oxygen-free air, carbon dioxide, or combinations thereof. The Protective Environment may also include minimization or avoidance of high shear stresses imparted on the stent material(s)85during processing.

Without intent on limiting, the coating30may be comprised of at leaset one of the coating materials31selected from the group of: absorbable polymers; acrylate-based materials; acrylic; alkyds; alginates; amorphous polymers; 3-aminopropyltrimethoxylsilane (APS); 3aminopropyltriethoxysilane (C9H23NO3Si); biostable polymers; biodegradable polymers; C10 polymer; C19 polymer; C19 polymer with hydrophobic and hydrophilic polyvinyl-pyrrolidinone groups; collagen; copolymers of DL-Lactide and glycolide; copolymers of DL-Lactide and L-lactide; copolymers of L-lactide and D-lactide; copolymers of L-lactide and DL-lactide; copolymers of DL-lactide and .epsilon.-caprolactone; crystalline polymers; cross linked poly vinyl alcohol (PVA) and gelatin; crystalline materials; degradable polymers; dissolvable polymers; durable polymers; epoxy-based materials; erodible polymers; ethylene copolymers; fluoropolymers; gelatin; heparin; high molecular weight polymers; hydrophilic materials; hydrophobic materials; hydrocolloids; hydroxyapatite; hydrophilic polyvinyl-pyrrolidone; hydrophobic hexyl methacrylate; hydrogels; hydrolyzed collagen; hydrophobic hexyl methacrylate and hydrophilic vinyl pyrrolidinone and vinyl acetate monomers; hydrophobic butyl methacrylate; iodine; lactide-based materials; light curing materials; low molecular weight polymers; lubricious materials; parylene; stent materials85listed herein; materials having glass transition temperature less than 40 degrees centigrade; materials having a glass transition temperature at or above 40 degrees centigrade; mixtures of poly(DL-Lactide) and poly(glycolide); mixtures of poly(DL-lactide) and poly(L-lactide); mixtures of poly(DL-lactide) and poly (.epsilon.caprolactone); mixtures of poly (DL-Lactide), poly(glycolide), and/or poly(L-Lactide); mixtures of poly(L-lactide) and poly(D-lactide); mixtures of amorphous polymers and semi-crystalline polymers; mixtures of poly (DL-lactide), poly (L-lactide), poly(glycolide), and poly(.epsilon.caprolactone); mixtures comprised of greater than 0 wt. % to 75 wt. % poly(glycolide) and the remainder poly(DL-lactide); mixtures comprised of greater than 0 wt. % to 85 wt. % poly(L-lactide) and the remainder poly(DL-lactide); mixtures comprised of greater than 0 wt. % to 85 wt. % poly(.epsilon.caprolactone) and the remainder poly(DL-lactide); modified derivatives of .epsilon.-caprolactone polymers; moisture curing materials; olefins; oxides; photo-curable hydrogels; phosphorylcholine; phosphates; platinum; polyacrylates; polyalkylene esters; polyamides; polyamides esters; poly (n-butyl methacrylate); polycaprolactone; poly (.epsilon.-caprolactone); polyethylene glycol; poly-DL-Lactide; poly (L-lactide)/poly (butylene succinate-co-L-lactate) blends; poly trimethyl carbonate; polyesters; poly (ethylene succinate); polyhydroxyalkanoates; poly-L-lactide; poly (L-lactide); poly (D-lactide); poly (D,L-lactide); poly (DL-lactide); poly (D,L-lactide) or poly (DL-lactide) having a degradation time between 3 months to 24 months where the degradation time equals the time to substantially complete mass loss of the coating; poly (D,L-lactide) or poly (DL-lactide) having a degradation time equal to or less than 3 months where the degradation time equals the time to substantially complete mass loss of the coating; poly (DL-lactide) or poly (DL-lactide) having a degradation time equal to or greater than 24 months where the degradation time equals the time to substantially complete mass loss of the coating; DL-lactide and glycolide copolymer having a degradation time between greater than 0.0 months to 24.0 months where the degradation time equals the time to substantially complete mass loss of the coating; DL-lactide and glycolide copolymer having a degradation time equal to or greater than 24.0 months where the degradation time equals the time to substantially complete mass loss of the coating; DL-lactide/glycolide copolymer(s) of any monomer ratio; poly (DL-lactide-co-glycolide); poly (D,L-lactide-co-glycolide) glycolide; poly (D,L-lactide-co-glycolide) lactide; L-lactide/D-lactide copolymers of any monomer ratio; L-lactide/DL-lactide copolymer(s) of any monomer ratio; povidone-iodine (PVP-1); any chemical complex of polyvinylpyrrolidone and elemental iodine; any polymer and radiopaque materials; lactones; L-lactide copolymer(s); L-lactide/glycolide copolymer(s) of any monomer ratio; L-lactide/.epsilon.-caprolactone copolymer(s) of any monomer ratio; Polymer(s) having degradation time 0.5 months to 48 months; Polymer(s) having degradation time equal to or less than 0.5 months; Polymer(s) having degradation time equal to or greater than 48 months; biodegradable Polymer(s) having molecular weight (Mw) 10 kg/mol to 220 kg/mol; biodegradable Polymer(s) having molecular weight (Mw) equal to or less than 10 kg/mol; biodegradable Polymer(s) having molecular weight (Mw) equal to or greater than 220 kg/mol; any material that temporarily prevents the substantial penetration of water into the stent material(s)85comprising the stent's wall thickness13; any material(s) that prevent the substantial penetration of water into the stent material(s)85comprising the stent's wall thickness13for a period of time within the range of greater than 0.0 minutes to less than about 6.0 months after the deployment of the stent10; any material(s) that prevent the substantial penetration of water into the stent material(s)85comprising the stent's wall thickness13for equal to six months to less than about five years; any material(s) that temporarily controls the penetration of water into the stent material(s)85comprising the stent's wall thickness13; any material(s) that control the substantial penetration of water into the stent material(s)85comprising the stent's40wall thickness13for a period of time within the range of greater than 0.0 seconds to less than about 3.0 months after the deployment of the stent10within the treatment site35; any material(s) that control the substantial penetration of water into the stent material(s)85comprising the stent's40wall thickness13for a period of time of equal to about 3 months to about less than 5 years after the deployment of the stent10within the treatment site35; any material(s) that increase the storage stability of wall thickness13of the stent10at ambient storage conditions; any material(s) that increase the storage stability of the wall thickness13of the stent10at temperatures above 23.degree. C; any material(s) that increase the storage stability of the wall thickness13of the stent10at a relative humidity above 30% relative humidity; any material(s) that affect the pH of the treatment site35after deployment of the stent10within the anatomical lumen36equal to or below about 7.4 pH; material(s) that affect the pH of the treatment site35after deployment of the stent10within the anatomical lumen36equal to or above about 7.4 pH; poly (butylene succinate) (PBS); polycaprolactone copolyglycolic acid; polycaprolactone glycerylmonostearate; polysaccharides; polytrimethylene carbonate; polyethylene co-vinyl acetate; polyolefins; polyvinyl pyrrolidinone (PVP); polyvinyl alcohols; polyethylene glycol; polyvinyl esters; proteins; resorbable polymers; resorbable excipients; styrene-based materials; starch acetate; styrene isoprene butadiene (SIBS) Block copolymers; terminal diols; urethane based materials; vinyl-based materials; wax; carnauba wax; beeswax; animal waxes; vegetable waxes; mineral waxes; synthetic waxes; petroleum waxes; homopolymer(s); copolymer(s) thereof; terpolymer(s) thereof; complexes thereof; combinations thereof; derivatives, analogs, and functional equivalents.

The stent10may be incorporated into a stent-graft254as depicted inFIG. 108. The stent-graft is comprised of the stent10and a graft255. The graft255is comprised of tube-shaped material that covers all or part of the inner surface17and/or the outer surface16of the stent10. The graft255may be attached or detached from the stent10. The graft255may be comprised of the bioresorbable stent material(s)87or durable materials. The graft255may be comprised of solid or porous material(s).

The applications or treatments include: a vascular stent; a peripheral vascular stent; a carotid stent; a cerebral stent; a cell transportation device; a cell growth platform; an endovascular application; an endovascular application in the popliteal artery; a device for supporting an anatomical lumen; a device for reinforcing an anatomical lumen; a device for patching a defect, tear or hole in an anatomical lumen; a device for delivering a drug or drugs to or within an anatomical lumen; a device for the treatment of lesions; a device for the treatment of lesions less than 24 millimeters in length; a device for the treatment of lesions equal to or greater than 24 millimeters in length; a device for treatment of lesions located in in arterial or saphenous veins or grafts; a device for treatment of lesions located in unprotected left main; a device for the treatment of ostial lesions; a device for treatment of lesions located at a bifurcation; a device for the treatment of previously stented lesion; a device for the treatment of calcified lesions; a device for the treatment of three-vessel disease; a device for the treatment of coronary artery within the range of greater than 0.00 millimeters to 4.0 millimeters in diameter; a device for the treatment of coronary artery equal to or greater than 4.0 millimeters in diameter; a renal stent; a iliac stent; a superficial femoral artery stent; a urethral stent; a ureter stent; a urinary stent; a biliary stent; an implantable scaffold; a drug delivery scaffold; a drug eluting scaffold; a vascular scaffold, a drug eluting vascular scaffold; a tracheal stent; a large bronchi stent; a nasal stent; a gastrointestinal stent; an esophageal stent; a drug delivery stent; a drug delivery device; a self-expandable stent; a balloon-expandable stent; a ratcheting stent; a modular stent; a bifurcated stent; a stent-graft; an abdominal aorta stent-graft; a birth control device; a bone replacement device; a nerve guide; an orthopedic device; an intrauterine device (IUD); an embolic filter; an anatomical lumen repair or splicing device; a device for local delivery of active ingredient(s)34to tubular shaped lumen or organs for treatment of cancer; a device for treatment of colon or rectal cancer; a device for the treatment of cancer; an implant; a patch; a percutaneous coronary intervention (PCI) device; a plug; a mechanical support device; a reinforcement device; a repair device; an attachment device; an oncology treatment device; a device for treatment of cancer within or near an anatomical lumen; a device to assist in remodeling of diseased anatomical lumens; a device for the treatment of angina; a device for revascularization; a device for treatment of calcified lesions; a device for prevention of thrombosis; an endovascular aneurysm repair (EVAR) device; an abdominal aorta aneurysm repair device; an iliac artery repair treatment device; a superficial femoral artery treatment device; a tissue engineering application (bone, cartilage, blood vessels, bladder, skin, tissue, muscle, etc.); a bone fixation device; bone plates; a temporomandibular joint repair or replacement; a medical textile; a repair; a transparent thin film transistor; a transparent semiconductor; a suture anchor; a surgical mesh; a device for reconstruction, or replacement/repair of ligaments; a device for repair, reconstruction, or replacement of rotator cuffs; a device for repair, reconstruction, replacement of hollow organ tissue; a suppository; a sinus stent; a tissue reinforcement device; an implantable device; a patch; regenerative medicine; a valve; a heart valve; and a vena cava filter. In other embodiments, the present invention may be applied to other devices, end-use applications and/or treatments.

In an embodiment, the packaged stent10and/or unpackaged stent10including or excluding the catheter37are sterilized before delivery into the anatomical lumen36. Sterilization results in the stent10being freed from viable microorganisms. The stent10may be freed from viable microorganisms by destroying the microorganisms. Without intent on limiting, the sterilized stent10must be free of viable microorganisms that include bacterial and fungi (yeast/mold) such as yeast (Candida albicans), mold (Aspergillus Niger), bacteria (E. coli, Pseudomonas, Staphylococcus aureus). Without limitation, the packaged or the unpackaged stent10including or excluding the catheter37and/or packaging may be sterilized with at least one of the following sterilization processes: (1) gamma irradiation (e.g., radioactive Cobalt60); (2) electron beam irradiation (e.g., e-beam)/X-ray; (3) ethylene oxide (Eta); (4) low temperature plasma, (5) molding processes; (6) steam and (7) dry heat, (8) ultraviolet light, and (9) any other process capable of sterilizing the components described herein. The stent10, catheter37and/or the packaging may be exposed to a dose of irradiation between about 10 to about 35 kGy. In other embodiments, the stent10, the catheter37and/or the packaging may be exposed to a dose of irradiation equal to or greater than about 35 kGy or exposed to a dose of irradiation equal to or less than about 10 kGy. Aseptic production and packaging environments may also be used. Depending on the application, the minimum sterility requirements may be explained in SAL-6 and SAL-3. Those skilled in the art of sterilization of medical devices may perform sterilization according to industry standards. Care must be taken to minimize the impact of sterilization on the molecular weight of the stent material(s)85, the crystallinity of the stent material(s)85, the mechanical properties of the stent material(s)85, and/or the efficacy of the active ingredient(s)34during sterilization.

The sterilized stent10may be further processed to stabilize the stent material(s)85within the stent10. The sterilized stent10may be further processed to stabilize the stent material(s)85by heating the stent10in at least one cycle above about the ambient temperature but below the glass transition temperature of some or all the stent material(s)85comprising the stent10within the range of greater than 0.0 minutes to 24.0 hours to stabilize the physical and/or mechanical properties of the stent10. In other embodiments, the sterilized stent10may be heated to above ambient temperature but below the glass transition temperature of some or all the stent material(s)85comprising the stent10for equal to or greater than 24 hours. In an embodiment the sterilized stent10is comprised of at least one part or completely comprised of post-processed stent material(s)85having a weight average molecular weight (Mw) greater than 110,000 g/mol after sterilization and/or having a weight average molecular weight (Mw) greater than 110 kilodaltons (kDa) and/or having an Inherent Viscosity (IV) greater than about 1.2 dl/g.

In an embodiment, the stent10is configured to partially or fully degrade by hydrolysis after deployment of the stent10within the treatment site35within the anatomical lumen36, which results in a substantially complete loss of the mass of the stent10after the treatment time. The stent10may partially or fully degrade by the cleaving98of the molecular chains comprising the post-processed bioresorbable stent material(s)85within the stent10from a higher molecular weight to a lower molecular weight within the treatment site35, which results in a substantially complete loss of the mass of the stent10after the treatment time. In other embodiments, the stent10may partially or fully degrade by corrosion or bio-corrosion within the treatment site35, which results in a substantially complete loss of the mass of the stent10after the treatment time. The stent10may also partially or fully degrade by cleaving98the molecular chains comprising the stent material(s)85and corroding or bio-corroding the reinforcement(s), which results in a substantially complete loss of the mass of the stent10after the treatment time. The constituents of the stent10may be partially or fully configured to be solubilized in water and/or biological fluids and partially or fully transported away from the treatment site35.

Part or all the stent10may degrade by hydrolysis. In another embodiment the stent10may configured to degrade by a bacterial attack. The bioresorbable stent10, during the initial phases of degradation, may degrade by the long or high molecular weight chains hydrolyzing into lower molecular weight oligomers. The rate of hydrolysis may be accelerated or de-accelerated by acids or bases incorporated into the stent10. The rate of hydrolysis is dependent on moisture content and temperature of the stent10. The crystallinity of the stent material(s)85and blends of the stent material(s)85within the stent10affect the rate of degradation of the stent material(s)85comprising the stent10, where crystalline stent material(s)85degrade slower than amorphous stent material(s)85and/or hydrophobic stent material(s)85degrade slower than hydrophilic stent material(s)85.

While several particular forms of the invention have been depicted and described, it will also be apparent that various modifications can be made without departing from the scope of the invention. For example, and without limitation, the strut pattern171may have a lesser or greater number of rings19than what is depicted inFIG. 114. As a further non-limiting example, the strut pattern171may have any number of open or closed cells22circumferentially arranged to encircle the stent10central axis14. InFIG. 114, there are three W-shape cells22that are circumferentially arranged, although a lesser or greater number of W-shape or other shapes may be implemented in a strut pattern192of other embodiments. Moreover, the strut pattern171can have any number of W-shape or other shape open or closed cells22arranged axially along the entire longitudinal length15of the stent10in other embodiments. InFIG. 114, there are eighteen W-shape closed cells axially arranged, although a lesser or greater number of W-shape or other shapes may be implemented in the strut pattern171of other embodiments.

In other embodiments, adjustments to the previously specified strut pattern171design may be made to compensate for unique characteristics of the stent material(s)85used to construct the stent10, manufacturing processes used to produce the stent10, end-use application, or equipment utilized to deploy the stent10. Some or all the crests189may be connected to some or all the troughs190of adjacent rings19with the link struts21, some or all the crests189may be connected to some or all the crests189of adjacent rings19with the link struts21, some or all the troughs190may be connected to some or all the troughs190of adjacent rings19with the link struts21, or combinations thereof. Some or all the linear ring struts20and/or link struts21may include curved or bent portions; some or all the linear ring struts20and/or link struts21may include a serpentine configuration; some or all the linear ring struts20and/or link struts21may include at least one feature such as and without limitation indentations, radii, grooves, cuts, thru holes and other features that enhance operability of the stent10during crimping, deployment and/or treatment. In other embodiments, the shape of the cells22may be a mixture of different shapes and configurations. There may be more or less than eight linear ring struts20and/or more or less than two link struts21to form the cells22. The size and shape of the cells22may vary in different portions of the strut pattern171. For example, the cells22may be different near the proximal25and distal26ends than near the central portion of the stent10. The width279of the linear ring strut20and the width280of the link strut21and thickness13of the linear ring struts20and/or the link struts21may vary in one or more portions of the stent10. The thickness13of the stent10may be thinner in one or more portions of the stent10such as thinner near the proximal25and distal26ends than near the center portion of the length15so that stress concentrations do not develop at the intersection of the stent10and the anatomical lumen36. The exemplary strut pattern171depicted inFIG. 114has nineteen rings19. In other embodiments, there are more or less rings19. There could be more rings19used within the same length15, for example, to decrease the linear ring strut width204and/or thickness13while maintaining substantially the same amount of support to the anatomical lumen36. In another variation, the link struts21may be on an angle and/or curved to facilitate longitudinal bending of the stent10rather than being straight and parallel to the central axis14as depicted inFIG. 114. Moreover, some or all the areas subjected to higher stress during crimping, delivery, deployment, and/or treatment time like, without limitation, at curved hinge element281may be reinforced by thickening or thinning the affected areas.

The cross-sectional profile of the linear ring struts20and/or link struts21may vary at least one time or not vary within the stent10. The wall thickness13and/or cross-sectional shape of the of the linear ring struts20and/or link struts21may be the same in the crest(s)189and/or the trough(s)190as in the remaining portion of the ring(s)19or the wall thickness13and/or cross-sectional shape of the some or all of the linear ring strut(s)20and/or link strut(s)21at or near the crest(s)195and/or the trough(s)196may be different than the remaining portion of the ring(s)19. The wall thickness13at or near some or all the crest(s)189and/or trough(s)190may be thicker than the wall thickness13in some or all of the remaining portions of the ring(s)19or the wall thickness13at or near some or all of the crest(s)189and/or trough(s)190is thinner than the wall thickness13in some or all of the remaining portions of the ring(s)19. The linear ring strut width279and/or link strut width280at or near some or all of the crest(s)189and/or trough(s)190may be wider than the linear ring strut width279and/or link strut width280in some or all of the remaining portions of the ring(s)19or the linear ring strut width279and/or link strut width280at or near some or all of the crest(s)189and/or trough(s)190may be narrower than the linear ring strut width279and/or link strut width280in some or all of the remaining portions of the ring(s)19.

Some or all the crest(s)189and/or trough(s)190may include at least one open loop to improve flexibility and/or reduce stress concentrations at some or all the crest(s)189and/or trough(s)190. The strut pattern171may include at least one radius or fillet located at least at one intersection(s) of the linear ring strut(s)20and link strut(s)21. Some or all the linear ring struts20and/or the link strut(s)21may include a serpentine configuration located between some or all the crest(s)189and trough(s)190. Some or all the linear ring strut(s)20and/or the link strut(s)21may include a straight configuration located between some or all the crest(s)189and trough(s)190. Some or all the linear ring strut(s)20and/or link strut(s)21may include a serpentine configuration located between some or all the curved hinge elements281. Some or all the linear ring strut(s)20and/or the link strut(s)21include a straight configuration located between some or all the curved hinge elements281. The need for including the aforementioned features within the strut pattern171depends on the requirements of the treatment and the need can be experimentally determined by those skilled in the art of stent strut design.

Although it is preferred to convert the stent material(s)85and/or composite material(s) into the stent10using processes described herein, it will be apparent that modifications to the processes or sequences of processes can be made without departing from the scope and intent of the invention. Moreover, the stent10of the present invention or the processes of forming the stent10may be any single embodiment or any combinations of at least two embodiments described herein in all possible variations unless otherwise indicated herein or otherwise clearly contradicted by context. The variations of features are virtually endless and therefore it is impossible to list all these herein.

The composition of the stent material(s)85and/or reinforcement(s) may be tuned to meet the specific mechanical properties, the physical dimensions, degradation rate, and/or resorption rate required by the specific end-use application or treatment. There is almost an endless number of variations of the ratios of bioresorbable monomer(s), polymer(s), and copolymer(s) specified herein that are useful in the blend(s) of polymer(s) and/or copolymer(s) specified herein that can produce the stent material(s)85meeting the requirements of the broad number of end-use applications. There is almost an endless number of variations of ratios chemical elements specified herein that can produce the reinforcement(s) or alloys comprising the reinforcement(s) meeting the requirements of the broad number of end-use applications. It should be appreciated that any possible ratios of the monomer(s), the polymer(s), the copolymer(s), and the chemical element(s) mentioned herein may be included within the stent10. It should also be appreciated that the addition of trace amounts of chemical element(s) not mentioned herein, or combinations of chemical element(s) not specifically mentioned herein but produce a material having substantially the same mechanical properties, degradation properties, and other properties as those described herein are all within the scope of the present invention.

Polymer(s) are comprised of molecules having different chain lengths. The length of the chain can be determined by the molecular weight or molecular mass of the polymer(s). This specification describes ultra-high molecular weight polymer(s) in terms of weight average molecular weight (Mw) and Inherent Viscosity (IV). It should be appreciated that the same polymer(s) may be described in terms of number average molecular weight (Mn) or higher average molecular weights (Mz, Mz+1) and that these alternative measurements may be the same polymer(s) incorporated into the present invention and if these polymer(s) are the same that they fall within the scope of the present invention.

The operational steps for forming the stent material(s)85and/or composite material(s) into the stent10may be performed in a continuous process. The operational steps for forming the stent material(s)85and/or composite material(s) into the stent10may be performed in a discontinuous or batch processes. In an embodiment, some or all the processing steps described herein may be combined into one or more processing steps or some or all the operations or the processing steps described herein may be disaggregated into multiple steps to form the stent10. Moreover, some or all the processing steps described herein may be performed in a different order or sequence when forming the stent10from the stent material(s)85and/or the composite material(s). It should be appreciated that the stent10may include some or all the features described herein.

Definitions

“Active ingredient” means any substance that is biologically active, therapeutically active, or an active pharmaceutical ingredient (API).
“Alloy” means a material composed of at least two metals or a metal and a nonmetal. An alloy may be a solid solution of the elements (a single phase), a mixture of metallic phases (two or more solutions), or an intermetallic compound with no distinct boundary between the phases.
“Anatomical lumen” means a cavity, duct, or a tubular organ.
“Axial” and “longitudinal” mean a direction, line, or alignment that is parallel or substantially parallel to the central axis of a cylindrical structure or the long length of a film, sheet or tube.
“Bioresorbable” means the breakdown of a compound into a simpler substance, materials or their degradative byproducts that are absorbed and/or eliminated by the body, or substances that do not require mechanical removal. The term “bioresorbable” can also generally refer to any material that is: absorbable; bioabsorbable; biodegradable; bio-adsorbable; bioremovable; bio-corrodible; bio-erodible; dissolvable; degradable; soluble; metabolizable; erodible in physiological conditions; degradable via hydrolytic mechanism; able to disappear via phagocytosis; able to disappear via chemical breakdown by physiological environment; broken down by a living body and does not require mechanical removal; corrodible; eliminated by a living body; eliminated by the a living body without mechanical removal; eliminated by cellular activity; eventually dispersed throughout the living body; a macromolecule that experiences cleavage of the main chain and is broken down into by-products and can be eliminated by biological pathways such as through the kidneys or lungs; soluble in blood or broken down to materials that are soluble in blood; or any substance that partially or fully disappears or losses mass within the living body after deployment.
“Chemical element” or “element” means a pure chemical substance consisting of a single type of atom distinguished by its atomic number, which is the number of protons in its atomic nucleus.
“Circumferential” and “circumferentially” mean a direction along a circumference of a stent or circular structure.
“Copolymer” means a chemical compound formed by uniting the molecules of at least two different compounds or monomers.
“Cleaved” or “Scission” means that a molecule is split, by breaking a chemical bond.
“Degradation rate” means the speed at which loss of mass of the material within the implanted stent occurs.
“Degradation time” means the time to complete mass loss of the material within the stent and/or the coating.
“Degree of polymerization” means the number of monomeric units within a molecule of a macromolecule, polymer or oligomer.
“Delivery” means introducing and transporting the stent through an anatomical lumen to a desired treatment site and/or active ingredient to the treatment site.
“Deploy,” “Deployed,” and “Deployment” means positioning or implantation of the stent within the anatomical lumen so that it can perform the treatment.
“Dry,” “dries,” or “dried” mean including no or very little liquid or volatile substances.
“Drug” (also known as medicine) means a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.
“Ductile” means the capability of the material(s) to be changed in shape and/or size under stress and/or strain.
“Durable” means the material can withstand wear, environmental conditions, and pressure, and generally remains substantially in original implanted location, shape, and/or form greater than about five years or regularly for the life a patient.
“Erodes” or “Erosion” means that the material(s) within the stent are gradually reduced and/or relatively slowly destroyed after deployment of the stent within the anatomical lumen.
“Expand” or “Expanding” means become or make larger.
“Fiber” means any nano filament, microfilament, filaments, belts, monofilaments, multi-filaments, strands, strips, strands, straps, tapes, threads, twine, wires, yarns, or any objects having a length that is greater than its thickness. “Film” means a thin layer of the material(s).
“Fracture” means when the specimen breaks into multiple pieces, cracks, ruptures or is disrupted.
“Graft” means an implantable member comprised of a living or artificial material that can replace or repair a diseased or injured cells, tissue, organ or combinations thereof.
“Homopolymer” means a chemical compound formed by uniting the molecules of one compound or monomer.
“HRE” means heavy rare earth chemical elements including Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu or chemical elements having atomic number between 62 and 71).
“Inherent Viscosity” means the natural logarithm of relative viscosity divided by polymer concentration in dilute solutions.
“Bond” (aka “weld line” or “knit line”) means when two polymers join to form an object.
“Layer” means a single thickness of material laid or lying over or under another.
“Luminal” means the innermost surface having the shortest radial distance from the central axis of the stent.
“Shaft” means a rod, shaft, bar or other object around which material may be shaped.
“Mechanical property” means strength, tensile strength, yield strength, ultimate tensile strength, elastic modulus, modulus of elasticity, Young's modulus, flexural modulus, bending modulus, modulus of rupture, flexural strength, fracture strength, ductility, stiffness, impact strength, Charpy impact strength, compressive strength, fatigue strength, elongation-to-break, elasticity, plasticity, fatigue limit, endurance limit, Poisson's ratio or combination thereof.
“Melt” or “Melting” mean the process of a substance undergoing a phase transition from a solid into a liquid.
“Metal Chemical Element” means the chemical elements having the symbols Ag, Al, Au, Ba, Be, Bi, Ca, Cd, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Gd, Ge, Hf, Ho, In, Ir, K, La, Li, Lu, Mg, Mn, Mo, Na, Nb, Nd, Ni, Pd, Pr, Pt, Re, Rh, Ru, Sb, Sc, Si, Sm, Sn, Sr, Ta, Tb, Tc, Ti, Tm, V, W, Y, Yb, Zn, and Zr.
“Monomer” means a molecule that can combine with others to form a polymer.
“Molecular chain” means at least two like or different atoms linked together by forces.
“Nominal diameter” means the sum of the inner diameter and the outer diameter of the stent prior to crimping or deployment divided by two.
“Oligomer” means a molecule containing a few monomer units (up to about five monomer units).
“Passivation layer” means a shielding outer-layer so that base material is less affected by environmental factors.
“Physical properties” or “mechanical properties” mean the modulus of elasticity, shear modulus, bulk modulus, Young's modulus, yield strength, elongation-to-break, degradation rate, molecular weight, solubility, viscosity, melt index, density, and resorption rate. All physical properties and mechanical properties data provided herein are at room temperature (about 23-24.degree. C) unless otherwise noted.
“Physiological conditions” mean conditions within the human body including or conditions simulating the conditions within the human body.
“Polymer” means natural or synthetic compounds consisting of repeating units linked by chemical bonds.
“Post-processed” means after completion of all processes that form the material(s) into the stent, including crimping and sterilization.
“Radiopaque” means the relative inability of electromagnetic radiation, particularly X-rays, to pass through a particular material.
“Radial strength” means the ability of a stent or tube to resist radial compressive forces.
“Radial Expansion Ratio” means the tube larger ending diameter (after being deformed) divided by the tube smaller starting diameter (before being deformed).
“Restenosis” means the reoccurrence of stenosis in a blood vessel or heart valve after it has been treated by, for example, balloon angioplasty, stenting, or valvuloplasty.
“Resorb” means a loss of the stent materials from the implantation site by destruction and/or physiological means.
“Resorption rate” means the speed in which the material substantially loses all its mass during the time the stent is implanted within the anatomical lumen.
“Resorption time” means the time that is necessary for the complete mass of the stent to disappear or be removed from the anatomical lumen, wherein the time is measured starting from the time the stent is implanted in the anatomical lumen and ending with the time there is no stent mass remaining within the anatomical lumen.
“RE” means rare earth chemical elements including La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, La, Lu, Sc, and Y.
“Scaffold” means a mechanical structure or framework that provides support, holds tissue or cells together, or maintains tissue contour; a scaffold is often used when providing temporary functionality.
“Sheet” means a relatively thin, normally rectangular or square form, piece, plate or slab comprised of at least one fiber.
“Shrink” means to become or make smaller in size or amount; to contract or cause to contract; to become smaller or more compacted.
“Solvent” means “a substance in the form of a liquid, solid, or gas that dissolves a solute (a chemically different liquid, solid, or gas) resulting in a solution.
“Solid” means firm and stable in shape; substantially free of liquid or fluid.
“Sintering” means the process of partially or fully interconnecting and/or coalescing the particles, layers, fibers, sheets, films, layers, or combinations thereof into a solid or porous mass by heating and/or compressing them without liquefaction of the material(s) comprising the particles, layers, fibers, sheets, films, or layers.
“Solution” means a homogeneous mixture of at least two substances that can be a solid, liquid, or gas, where such mixture is comprised of a solute, which is a substance dissolved in another substance, known as a solvent.
“Soluble” means the ability of one compound to dissolve in another compound.
“Spiral” means winding in a continuous curve around a central point usually getting farther away from it.
“Stent” means a short narrow tube often in the form of a mesh that is inserted into the lumen of an anatomical vessel (as an artery or bile duct).
“Sterilized” means a state of being free from viable microorganisms.
“Stress” means the applied load divided by the original cross-sectional area of the specimen.
“Strain” means the change in the specimen's length divided by its original length.
“Stiffness” means the rigidity of the wall thickness or to the extent the wall thickness resists deformation in response to an applied force.
“Swollen” means object become larger in size, typically because of accumulation of liquid. A swollen material may also be a gel.
“Treatment” means administration or application of remedies to a patient for a disease or an injury; medicinal or surgical management; therapy or the action or manner of treating a patient medically or surgically.
“Treatment time” means the duration of the treatment.
“Treatment site” means the location or position of deployment of the stent.
“Tube” means a hollow elongated cylinder such as a channel, conduit, duct, or pipe.
“Therapeutic agent” means any substance that when administered in a therapeutically effective amount to a patient has a therapeutic beneficial effect on the health and well-being of the patient such as without limitation curing a disease, slowing the progress of a disease, causing the disease to retrogress, or alleviating a symptom of a disease.
“Tissue” means any group of cells that in the aggregate perform the same function.
“Un-oriented tube” means that the tube has not been deformed.
“Volatile” means a substance that vaporizes readily at normal temperatures.
“Vaporize” means conversion of a solid or liquid into a gas.
“Void” means an empty space.
“Weight Percent” or “wt. %” means the weight percent of the component within the material or formulation wherein all components add up to 100 weight percent unless otherwise noted.
“about” and “approximately” mean numerical values or ranges that those skilled in the are would consider a value different from the exact number or outside the actual range to be close enough to be with the aegis of that number or range. At the very least, the terms “about” and “approximately” are understood to mean plus or minus.25 percent of a given numerical value or range starting and ending point.
“Substantial” or “substantially” mean that the object of the adjective or adverb is not a perfect example of such object but would be immediately known by those skilled in the art to warrant the general designation.
The terms “stent” and “scaffold” are used interchangeably herein and mean the same except where specifically noted to be different.
The terms “a,” “an,” and “the” are to be construed as referring to one or more of whatever the word modifies.
It is understood that use of singular throughout this application including the claims includes the plural and vice versa. It is understood that use of plural throughout this application including the claims includes the singular.
The term “may” is to be construed as referring to whatever the word refers to as being optional unless whatever the word refers to is mentioned in the claims herein, which would mean whatever the word refers to is included.

EXAMPLES

The following examples are presented to more particularly illustrate our invention and are not to be construed as limitations thereon.

Solid granules of raw stent material85comprised of two homopolymers of L-lactide (available from Corbion Purac, the Netherlands) were combined with the solvent86comprised of methylene chloride (aka, Dichloromethane-CH2Cl2) (herein after referred to as “DCM”) in a container and stirred until the homopolymer of L-lactide was liquefied by dissolving the homopolymers of L-lactide within the liquid solvent86to form the liquid solution83. The first homopolymer of L-lactide had a weight average molecular weight (Mw) of 2,000,000 grams per mole (g/mol) and Inherent Viscosity of 8.0 dl/g (hereinafter referred to as “PLLA”) (i.e. “F-5”) and the second homopolymer of L-lactide had a weight average molecular weight (Mw) of 221,000 grams per mole (g/mol) and Inherent Viscosity of 1.8 dl/g (hereinafter referred to as “PL-18”) (i.e. “F-2”) to make a blend (“B-87”). The weight average molecular weight (Mw) was determined by Gel Permeation Chromatography (GPC) in chloroform at 35.degree. C relative to polystyrene (PS) standards. The Inherent Viscosity (IV) was determined by viscometry of diluted polymer solutions. Measurements were performed in chloroform at 25.degree. C at a concentration of 0.1 g/dl.

The liquid solution83was a more viscous liquid than the liquid solvent86(e.g., greater than about 0.41 cP at 25.degree. C). The liquid solution83included 0.55 grams PL-80, 0.1 grams PL-18 and 21.5 grams DCM, which resulted in about a 2.9 weight percent (wt. %) Polymer Concentration that produced a solid film66comprised of about 84.6 weight percent (wt. %) PL-80 and 15.4 weight percent (wt. %) PL-18. The manual workstation suitable for making the solid film66consisted of a release media84, two stainless steel flat metal shims, a syringe, and a scraper. The release media84was comprised of a high-density polyethylene sheet; the stainless steel flat shims were about 0.13 millimeters thick and 200 millimeters long; and the scraper had a blade that was about 100 millimeters wide. The two flat stainless steel shims were taped onto the release media84so that the shims had a separation distance of about 75 millimeters so that the solid film66could be formed on the release media84within the space between the two shims.

The liquid solution83was drawn into the barrel of the syringe by inserting the open end of the syringe into the container so that the tip of the syringe was partially submerged within the liquid solution83and pulling on the plunger of the syringe to transfer at least enough of the liquid solution83to make one solid film66from the container into the barrel of the syringe. The liquid solution83within the syringe was then dispensed on the release media84between the two shims at the spreading start position. The scraper blade was positioned so that the left side of the blade rested on the left shim and the right side of the blade rested on the right shim near the spreading start position and behind the dispensed liquid solution83so that there was approximately equal overlap of the scraper blade on each of the shims. With the scraper blade resting on the shims and tilted so that it was oriented approximately sixty degrees from the release media84, the scraper blade was pulled toward the spreading end position at a relatively uniform rate of speed in a way that spread the liquid solution83in the form of the liquid film78on the surface of the release media84at a substantially uniform liquid film thickness88approximately equal to the height and length of the shims. The liquid film88was about 75 mm wide (about 3 inches wide). The liquid film78was allowed to dry on the release media84within an exhaust hood filled with air so that the volatile solvent86could substantially leave the liquid film78by evaporating or vaporizing to produce the thin solid film66comprised of the blend of PL-80 and PL-18 on the surface of the release media84. After the solid film66was substantially dry, the thin, adhered solid film66was removed from the release media84. Removal of the DCM from the liquid film78forms a solid film66that is temporarily attached (i.e., bonded) to the polyethylene sheet84. The solid film66was removed from the release media84by lifting one corner of the solid film66from the polyethylene sheet (the release media84) so that at least one part of the temporary bond between the solid film66and the polyethylene sheet84was broken so that the rest of the solid film66could be peeled off the polyethylene sheet84. Removing the solid film66from the polyethylene sheet84was like peeling wallpaper off a wall except there was no adhesive between the solid film66and the polyethylene sheet84. The solid film66thickness67was approximately 0.0039 mm when removed from the release media84. It is believed that treating the solid film66with an antistatic gun like the Zero Stat 3 Milty as the solid film66was peeled off the release media84made handing the solid film66easier. The liquid solution83having a 2.9 weight percent (wt. %) polymer concentration produced a liquid film thickness88that was approximately 33.3 times the solid film thickness67.

A first drug-eluting bioresorbable, implantable film66was made by mixing an active ingredient34comprising Everolimus with a liquid solution83comprising a pre-processed stent material85comprising poly (L-lactide) (aka “PLLA”) and a liquid solvent86comprising DCM. Alternatively, the active ingredient34, the stent material85and the solvent86were mixed at the same time. The liquid solution83including the Everolimus, PLLA and DCM was formed into a liquid film87having a rectangular cross-section on a release media84comprising polyethylene sheet84within a gaseous environment90comprising ambient air at normal room temperature (about 24 degrees Celsius). The liquid film87had a starting size of 4 inches wide by 6 inches long and 20 mils (0.508 mm) thick. The DCM86was removed from the liquid film87by vaporizing the solvent86into the ambient air. Removal of the solvent86from the liquid film87formed a solid PLLA film66that was temporarily attached (i.e., bonded) to the polyethylene release media84. The solid film66had ending dimensions that were about 4 inches wide by 6 inches long by 0.8 mils (0.020 mm) thick.

A second drug eluting bioresorbable, implantable film66was made from two different liquid solutions83. The first liquid solution83-A comprised an active ingredient34comprising Everolimus, a stent material85comprising PLLA and a solvent86comprising DCM and the second liquid solution83-B comprised a stent material85comprising PLLA and a solvent comprising 86 comprising DCM. The first liquid solution83-A was formed into a liquid film87-A having a liquid film width89of 4 inches and a length of 3 inches and a liquid film thickness88of 0.8 mils (0.020 mm) on a release media84comprising polyethylene sheet84. The second liquid solution83-B was formed into a liquid film87-B having a liquid film width89of 4 inches and a length of 3 inches and a liquid film thickness88of 0.8 mils (0.020 mm) on the same release media84so that the beginning of the second liquid film87-B was adjacent to the end of the first liquid film87-A. The liquid solution83-A and liquid solution83-B located at the adjacent ends of liquid film87-A and liquid film87-B merged to form on continuous liquid film87having a continuous length of 6 inches, wherein 3 inches of the length of the liquid film87forms an active ingredient free area142and a different 3 inches of the merged liquid film87forms an active ingredient storage area141. The solvents86was removed from the liquid film87-A and liquid film87-B to form one continuous solid film66having a total length of 6 inches, wherein 3 inches of the solid film66comprises an active ingredient free area142and another different 3 inches of the solid film66comprises an active ingredient storage area141.

The solid films were removed from the release media84by lifting one corner of the solid films66from the polyethylene sheet84and gradually peeling the solid films66that were adhered to the polyethylene sheet off the polyethylene sheet84. The solid films were submerged in water, which simulated physiological conditions, and the mass of the solid film66was lost as the solid film66dissolved by hydrolysis in the water with time. The Everolimus was released from the solid films66as the solid films66absorbed the water and as the solid films66lost mass.

About 10 percent of the top major surface73of the Bioresorbable, Implantable Film66described in Example 1 was covered with a drug-polymer coating30comprising the active ingredient34Everolimus and the coating material31Poly (DL-lactide) to form an active ingredient storage area141and an active ingredient free area143. About 25 percent of the top major surface73of the Drug-eluting Bioresorbable, Implantable Film66described in Example 2 was covered with a drug-polymer coating30comprising the active ingredient34Sirolimus and the coating material31a copolymer of L-lactide and glycolide to form an active ingredient storage area141and an active ingredient free area143.

The Bioresorbable, Implantable Film66of Example 1 and the Drug-eluting Bioresorbable, Implantable Film of Example 2, and the Drug-eluting Coated Bioresorbable, Implantable Film66of Example 3 were transformed into a roll52configuration comprising a beginning of the roll58, an end of the roll59, a roll inner diameter55, a roll outer diameter54, a roll length56, a roll passageway64, a roll central axis63and a roll thickness57comprising multiple said film thicknesses67in spiral cross section perpendicular to the roll central axis63, wherein said beginning of the roll58was disposed inside the roll passageway64and the end of the roll59was disposed outside the roll52. The rolls52were formed by wrapping the Bioresorbable, Implantable Film66, the Drug-eluting Bioresorbable, Implantable Film, and t Drug-eluting Coated Bioresorbable, Implantable Films66around a cylindrical-shaped shaft74.

The rolls52of Example 4 were transformed into an un-oriented tube42by forming a bond between the multiple, adjacent film thicknesses67within the roll thickness57. The film thicknesses67were bonded together by thermal welding and solvent bonding the film thicknesses67on a cylindrical-shaped shaft74. The un-oriented tubes42were removed from the shaft74. Some of the un-oriented tubes42were converted into oriented tubes38by radially expanding and/or axially elongating the un-oriented tube42.

The un-oriented tubes42and the oriented tubes38of Example 5 were transformed into stents10(aka Scaffolds) by laser cutting a strut pattern171in the un-oriented tubes42and the oriented tubes38. The stents10were crimped onto balloon catheters37and the stents10and catheters37were placed in a sealed packaging containing a Protective Environment. The package was e-beam sterilized at a dose below 40 kGy.

The stents10of Example 6 were transformed into coated stents10(aka coated Scaffolds) by covering the outer surface16of the ring struts20and link struts21with a coating30comprising 50% Everolimus and 50% poly (DL-lactide). The coated stents10were crimped onto balloon catheters37and the stents10and catheters37were placed in a sealed packaging containing a Protective Environment. The package was e-beam sterilized at a dose below 40 kGy.

Example 8: Bioresorbable Film Stent Having Controlled Delivery of Multiple Drugs

One solid film66including a first drug-polymer coating30covering approximately 10 percent of the film's bottom major surface73to make an active ingredient storage area141on one part of the one solid film's major surface73near the end of the roll59and a first active ingredient free area143on the remainder of the film's bottom major surface73, and a second drug-polymer coating covering approximately 10 percent of the film's top major surface73near the beginning of the roll58and a second active ingredient free area143on the remainder of the film's top major surface73, configured as a roll52having a roll thickness57, the film thicknesses67within the roll thickness57inter-connected with a bond65forms a tube38, wherein the one solid film66has a film length68of approximately 165 mm, a film width69of 100 mm and a film thickness67of approximately 0.005 mm and the coatings30have a coating thickness33of approximately 0.005 mm. The one solid film66comprises a stent material85comprising poly (L-lactide), the first coating30comprises an active ingredient34comprising approximately 25 vol. % paclitaxel and the remainder of the coating30comprises a stent material85comprising poly (D-lactide) and the second coating comprises an active ingredient34comprising fifty percent heparin and the remainder of the second coating comprises poly (L-lactide). The tube42comprises approximately 17 wraps of the one solid film66and has an inner diameter of 3 mm, an outer diameter of about 3.2 mm and a thickness of about 0.105 mm. There are approximately two wraps of the one film66covered with the coating30comprising the active ingredient34comprising paclitaxel and 13 of the uncoated solid film66wraps and approximately two wraps of the one film66covered with the coating30comprising the active ingredient34comprising paclitaxel. The tube thickness45has seven layers51, wherein the first layer51that is positioned near the inner diameter43of the tube42comprises one second coating thickness33, the second layer51comprises one film thickness67bonded to the underneath layer51, the third layer comprises one second coating thickness33bonded to the underneath layer51, the fourth layer comprises thirteen bonded solid film thicknesses67bonded to the underneath layer, the fifth layer51comprises one first coating thickness33bonded to the underneath layer51, the sixth layer51comprises one solid film thickness67bonded to the underneath layer51, and the seventh layer51positioned near the outer diameter44of the tube42comprises one first coating thickness33bonded to the underneath layer51. The tube42includes a strut pattern171that makes the tube42a stent10having a stent inner diameter12of 30 mm, a stent outer diameter11of 3.2 mm and a stent thickness13of 0.105 mm. The stent10is crimped onto a balloon catheter37and the stent10and catheter37are placed in a sealed packaging containing a Protective Environment. The package is Eto sterilized. Another stent10comprising the first active ingredient storage area141positioned on the top major surface73, the first active ingredient free area143positioned on the top major surface73of the solid film66, the second active ingredient storage area141on the bottom major surface73and the second active ingredient free area143positioned on the bottom major surface73. The stents10are configured for implantation in a segment of the peripheral artery below the knee for the treatment of arthrosclerosis (i.e., critical limb ischemia).

Example 9: Bioresorbable Film Stent Having Controlled Delivery of One Drug

One solid, film66(configured the opposite of what is depicted inFIG. 62) comprising a film width69, a film length68, two major surfaces73, four minor surfaces71and a film thickness67, wherein about eighteen and a half percent of the volume of the film thickness67(about 37.9 mm of the film length68starting at the end of the roll59) comprises a stent material85comprising poly (DL-lactide) having a pre-sterilized weight average molecular weight below 300,000 g/mol and at least 150 micrograms of an active ingredient34comprising sirolimus and the remaining approximately eighty-one and a half percent of the volume of the film thickness67(about 167 mm of the film length68ending at the end of the roll59) comprises a stent material85comprising poly (L-lactide) having a pre-sterilized weight average molecular weight of about 1,000,000 g/mol excluding the active ingredient34sirolimus. The film66conformable into a roll52having a beginning of the roll58disposed inside the roll's passageway64and an end of the roll59disposed outside the roll52, the roll52including a roll inner diameter55, a roll outer diameter54, a roll length56, a roll passageway64, a roll central axis63and a roll thickness57comprising 21 wraps of the film thicknesses67in spiral cross section perpendicular to the roll central axis63, the roll52converted into a tube38by interconnecting the film's66major surfaces with a bond65. The un-oriented tube42wall thickness45comprises two layers51, wherein one layer51comprising seventeen bonded film thicknesses67comprised of poly (L-lactide) is positioned on the inner diameter43of the un-oriented tube42and the second layer51comprising four bonded film thicknesses67comprising poly (DL-lactide) and the active ingredient34comprising sirolimus is positioned on the outer diameter44of the un-oriented tube42. The un-oriented tube42includes a strut pattern171that makes the un-oriented tube42a stent10, where the thickness13of the stent's10linear ring struts20and link struts21comprise one layer51comprising seventeen bonded film thicknesses67comprising poly (L-lactide) is positioned on the inner diameter12of the stent10and the layer51comprising four bonded film thicknesses67comprising poly (DL-lactide) and the active ingredient34comprising sirolimus is positioned on the outer diameter11of the stent10. Two additional stents10comprise the same construct as previously described, but the un-oriented tube42is in one stent10is radially enlarged so that the stent10includes molecular orientation of the stent materials85in the circumferential direction to increase the stent's10radial strength and in another stent10the un-oriented tube42is radially enlarged and elongated so that the stent10includes molecular orientation of the stent materials85in the circumferential and longitudinal direction to increase the stent's10radial and longitudinal strength. The self-expanding stents10are crimped onto a catheter37and the stent10and catheter37are placed in a sealed packaging containing a Protective Environment. The package is e-beam sterilized at a dose below 40 kGy. The stent's10are configured to be implanted in a segment of the peripheral artery.

Two solid films66(configured as depicted inFIG. 59), wherein a first solid, film66-A comprising stent materials85comprising a blend of poly (L-lactide) and poly (D-lactide), a film width69-A, a film length68-A, two major surfaces73-A, four minor surfaces71-A/72-A and a film thickness67-A and at least one additional solid, film66-B comprising poly (L-lactide) and iodine within at least one part of the additional solid, film66-B, an additional film width69-B having a size up to the size of the first solid, film, an additional film length68-B having an additional length up to the size of the first solid, film, two additional major surfaces73-B, four additional minor surfaces and an additional film thickness67-B, the film66-A and the additional film66-B having a cylindrical roll52configuration comprising a roll outer diameter54, a roll inner diameter55, a roll length56, a roll passageway64, a roll central axis63, wherein the roll52comprises multiple said film thicknesses in spiral cross section perpendicular to the roll central axis63.