Patent Publication Number: US-9833342-B2

Title: Tracheobronchial implantable medical device and methods of use

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application is a divisional application of U.S. patent application Ser. No. 11/507,913, filed Aug. 21, 2006, now U.S. Pat. No. 9,173,733, the disclosure of which is incorporated herein by reference. 
    
    
     FIELD OF INVENTION 
     Bioabsorbable implantable medical devices for the treatment of lesions caused by cancer of the tracheobronchial tree or cancer of the head, neck or chest. 
     BACKGROUND OF INVENTION 
     This invention relates generally to radially expandable endoprostheses which are adapted to be implanted in a physiological lumen. An “endoprosthesis” corresponds to an artificial device that is placed inside of a physiological lumen. A “lumen” refers to a cavity of a tubular organ such as a blood vessel or other physiological passageway. A stent, or implantable medical device, is an example of an endoprosthesis. Stents are generally cylindrically shaped devices which function to hold open or expand a physiological lumen, or to compress a lesion. A stent must be able to satisfy a number of mechanical requirements. For example, the stent must be capable of withstanding the structural loads, namely radial compressive forces, imposed on the stent as it supports the walls of the tubular organ. Accordingly, a stent must possess adequate radial strength. 
     In adults, primary cancer of the tracheobronchial tree or cancer of the head, neck or chest that extends into the tracheobronchial tree frequently causes lumen compromise and airway obstruction. “Tracheobronchial” refers to the physiological passageway from the throat to the lungs. In some methods of treatment, a compromised component of the tracheobronchial tree can be removed by laser treatment, mechanical debulking, electrocautery, brachytherapy, photodynamic therapy or cryotherapy. A stent can then be placed at the treatment site following removal of a comprised component to maintain the airway lumen to counteract collapse or edema. 
     Alternatively, a stent can be placed to help compress any lesion extending into the tracheo or bronchi without the need for removal of the compromised component. In some methods of treatment, a stent has been used to palliate patients with inoperable bronchogenic cancer, primary tracheal tumors and metastatic malignancies. 
     Stents which have been used in the tracheobronchial tree include metal, silicone and bioabsorbable stents. Metallic stents are generally made from an inert metal such as stainless steel, cobalt chromium and Nitinol. Some problems associated with known stent types delivered to the tracheobronchial region include inflammation, stent migration, epithelial damage, granulation tissue formation and mucous plugging. In addition, it is believed that known bioabsorbable stents designed for placement in the tracheobronchial region are not able to adequately combat inflammation caused by stent placement. 
     “Stent migration” refers to the gradual movement of the stent down the tracheobronchial tree after placement thereof. Stent migration of silicone stents in the tracheobronchial tree is common. “Mucous plugging” is an excessive production of mucous produced in response to the stent. Mucous plugging can cause interference with breathing. “Granulation tissue formation” is the formation of new tissue in response to a wound or other disruption of tissue. Excessive granulation tissue formation can cause a stent to be permanently lodged within a passageway complicating removal if required. Metal stents are especially susceptible to granulation tissue formation. Accordingly, a tracheobronchial stent which addresses these problems is desirable. 
     SUMMARY OF INVENTION 
     Devices and methods for treating a diseased tracheobronchial region in a mammal are herein disclosed. The device can be a stent which can include a sustained-release material such as a polymer matrix with a treatment agent. The stent can be a bioabsorbable stent and a treatment agent can be incorporated therewith. A treatment method can be delivery of a stent to a tracheobronchial region by a delivery device such as a catheter assembly. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG. 1  illustrates a side view of an embodiment of a stent of the present invention. 
         FIG. 2  illustrates a side view of an alternative embodiment of a stent of the present invention. 
         FIG. 3A  illustrates side view of a first alternative embodiment of a stent of the present invention. 
         FIG. 3B  illustrates side view of a second alternative embodiment of a stent of the present invention. 
         FIG. 3C  illustrates an embodiment of a braided stent with variable radial strength. 
         FIG. 3D  illustrates an embodiment of a coiled stent with variable radial strength. 
         FIG. 4A  illustrates an elevational view, partially in section, of a delivery system having a covered stent on a catheter balloon which may be used pursuant to methods of the present invention. 
         FIG. 4B  is a cross-section of the delivery system of  FIG. 4A  taken at line  2 - 2 . 
         FIG. 4C  is a cross-section of the delivery system of  FIG. 4B  taken at line  3 - 3 . 
     
    
    
     DETAILED DESCRIPTION 
     Embodiments of devices and methods for treating a diseased tracheobronchial region in a mammal, including, but not limited to, humans, are herein disclosed. In some embodiments, the device can be an implantable medical device such as a stent. Representative examples of implantable medical devices include, but are not limited to, self-expandable stents, balloon-expandable stents, micro-depot or micro-channel stents and grafts. In some embodiments, a treatment method can be delivery of a stent to a tracheobronchial region by a delivery device such as a catheter assembly. 
     In some treatment applications, a stent may only be required to be present in the tracheobronchial region for a limited period of time. To accommodate this, a stent can be made of a biodegradable, bioerodable or bioabsorbable polymer, hereinafter used interchangeably. A stent can also be made of a biostable or biodurable (hereinafter used interchangeably) or a combination of a biostable and biodegradable polymer. A stent made from a biodegradable polymer is intended to remain in the body for a duration of time until its intended function of, for example, maintaining luminal patency and/or drug delivery, is accomplished. After the process of degradation, erosion, absorption and/or resorption has been completed, none or substantially none of the biodegradable portion of the stent will remain in the tracheobronchial region. 
     In some embodiments, the stent may include a treatment agent. As used herein, treatment agents are intended to include, but are not intended to be limited to, drugs, biologically active agents, chemically active agents, therapeutic agents, and the like, and pharmaceutical compositions thereof, which can be used to deliver a treatment agent to a treatment site as described herein. Representative treatment agents include, but are not limited to, an anti-inflammatory, an anti-platelet, an anti-coagulant, a fibrinolytic, an anti-thrombonic, an anti-mitotic, an anti-biotic, an anti-allergic, an anti-oxidant, an anti-proliferative and an anti-migratory. The treatment agent may be incorporated within the body of the stent or within a polymer-based coating applied on or within the stent. 
     Tracheobronchial Stents 
       FIG. 1  illustrates an embodiment of a stent. Stent  100  is generally tubular and includes a lumen  102  with an abluminal surface  104  and a luminal surface  106 . Stent  100  can include a plurality of struts  108  connected by linking struts  110  with interstitial spaces  112  located therebetween. The plurality of struts  108  can be configured in an annular fashion in discrete “rows” such that they form a series of “rings” throughout the body of stent  100 . Thus, stent  100  can include a proximal ring  114 , i.e., proximal concentric end region, distal ring  116 , i.e., distal concentric end region, and at least one central ring  118 , i.e., middle concentric region. In some embodiments, proximal ring  114  and distal ring  116  can have a larger outer diameter than that of central rings  118 . For example, the outer diameter (OD) of central rings  118  can be from about 3.5 mm to about 25 mm, and in some embodiments, from about 8 to about 20 mm. The OD of proximal ring  114  and distal ring  116  can be from about 5.0 mm to about 30 mm, and in some embodiments, from about 10 to about 22 mm. Such configuration may reduce or eliminate stent migration. 
       FIG. 2  illustrates an alternative embodiment of a stent. Stent  200  is generally tubular and includes a lumen  202  with an abluminal surface  204  and a luminal surface  206 . Stent  200  can include a series of filaments  208  which can be interconnected in a braided, twisted or coiled fashion. Filaments  208  may be fabricated from a biodurable or biodegradable metal or polymer. Tubular stent  200  can include a proximal end  214 , a distal end  216  and at least one central portion  218 . In some embodiments, proximal end  214  and distal end  216  can have a larger outer diameter than that of central portion  218  similar to those ranges given with respect to  FIG. 1 . Stent  200  can be a self-expanding stent. 
       FIG. 3A  illustrates another alternative embodiment of a stent. Stent  300  is generally tubular and includes a lumen  302  with an abluminal surface  304  and a luminal surface  306 . Stent  300  can include a series of filaments  308  which can be interconnected in a braided, twisted, weaved or coiled fashion. Filaments  308  may be fabricated from a biodurable or biodegradable metal or polymer. Tubular stent  300  can include a proximal end  314 , a distal end  316  and at least one central portion  318 . In some embodiments, proximal end  314  and distal end  316  can have a larger outer diameter than that of central portion  318  similar to those ranges given with respect to  FIG. 1 . Stent  300  can be a self-expanding stent. 
       FIG. 3B  illustrates another alternative embodiment of a stent. Stent  301  is generally tubular and includes a lumen  303  with an abluminal surface  305  and a luminal surface  307 . Stent  301  can include a series of filaments  309  which can be interconnected in a braided, twisted, weaved or coiled. Filaments  309  may be fabricated from a biodurable or biodegradable metal or polymer. Tubular stent  301  can include a proximal end  315 , a distal end  317  and at least one central portion  319  similar to those ranges given with respect to  FIG. 1 . In some embodiments, proximal end  315  and distal end  317  can have a larger outer diameter than that of central portion  319 . Stent  301  can be a self-expanding stent. 
     In some embodiments, a stent according to the present invention can have variable radial strength along the stent length. For example, the stent can have higher radial strength at the proximal and distal ends relative to the central portions. In this aspect, the higher radial strength proximal and distal ends can serve as “anchors” after placement in the tracheobronchial tree. It is anticipated that higher radial strength proximal and distal ends can substantially minimize, or even prevent, stent migration. 
       FIG. 3C  illustrates an embodiment of a braided stent with variable radial strength. Stent  320  includes proximal end  322 , distal end  324  and at least one central portion  326 . Proximal end  322  and distal end  324  can have higher picks per inch, or pitch (hereinafter referred to interchangeably), which can give ends  322  and  324  higher radial strength relative to central portion  326 . “Pitch” is the density of material in a given unit of length. In some embodiments, a thin polymer fiber can be extruded, drawn and heat set to the dimensions ranging from about 0.003 inches to about 0.010 inches. The fibers can be wound onto a bobbin or spool and braided into a stent using a braiding machine. Braiding machines for stent fabrication are generally known by those skilled in the art. The pitch for central portion  326  of stent  320  can be predetermined by using the appropriate gear dimension in the braiding machine in the braiding machine to produce a predetermined picks per inch. Once central portion of stent  320  has been braided, the gear dimension in the braiding machine can be changed to accommodate fabrication of higher picks per inch of proximal end  322  and distal end  324 . In some embodiments, central portion  326  can have a pitch of about 40 to about 90 picks per inch while ends  322  and  324  can have a pitch from about 60 to about 100 picks per inch. In any case, the proximal and distal ends will have higher picks per inch as compared to the central portion. In some embodiments, ends  322  and  324  can be from about 1.0 mm to about 5.0 mm. After braiding, stent  320  can be heat set. For example, in braided stents comprised of poly-L-lactic acid, heat setting can be done at between about 120° C. to about 160° C. for about 10 to about 30 minutes. 
       FIG. 3D  illustrates an embodiment of a coiled stent with variable radial strength. Stent  321  includes proximal end  323 , distal end  325  and at least one central portion  327 . Proximal end  323  and distal end  325  can have a higher pitch angle, which can give ends  323  and  325  higher radial strength relative to central portion  327 . “Pitch angle” is defined as the angle between the direction of the fiber and longitudinal axis. In some embodiments, a thin polymer fiber can be extruded, drawn and heat set to the dimensions ranging from about 0.003 inches to about 0.010 inches. The fiber can be coiled onto a mandrel with a predetermined pitch angle for central portion  327 . Proximal end  323  and distal end  325  can be constructed using a higher pitch angle to increase radial strength. In some embodiments, central portion  327  can have a pitch angle of about 25° to about 70°, while ends  323  and  325  can have a pitch angle from about 50° to about 90°. In any case, the pitch angle at the proximal and distal ends will be higher than the central portion for increased radial strength. In some embodiments, ends  323  and  325  can be from about 1.0 mm to about 10.0 mm. After coiling, stent  321  can be heat set. For example, in coiled stents comprised of poly-L-lactic acid, heat setting can be done at between about 120° C. to about 160° C. for about 10 to about 30 minutes. 
     In general, a stent is designed so that the stent can be radially compressed (crimped) and radially expanded (to allow deployment). The stresses involved during compression and expansion are generally distributed throughout various structural elements of the stent. As a stent deforms, various portions of the stent can deform to accomplish radial expansion. In this aspect, the stent must be sufficiently malleable to withstand compression and expansion. 
     On the other hand, the stent must exhibit a certain degree of rigidity to maintain lumen patency during its lifetime. For a bioabsorbable stent, a lifetime can be from about 2 months to about 24 months depending on the intended application. Thus, a biodegradable stent is preferably fabricated from a polymer which allows for sufficient malleability during compression and expansion, and sufficient rigidity after deployment thereof. 
     Representative examples of polymers that may be used to manufacture or coat a stent, include but are not limited to, poly(N-acetylglucosamine) (Chitin), Chitosan, poly(hydroxyvalerate), poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolide), poly(L-lactic acid), poly(L-lactide), poly(D,L-lactic), poly(caprolactone), poly(trimethylene carbonate), polyester amide, poly(glycolic acid-co-trimethylene carbonate), co-poly(ether-esters) (e.g. PEO/PLA), polyphosphazenes, biomolecules (such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic acid), polyurethanes, silicones, polyesters, polyolefins, polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymers and copolymers other than polyacrylates, vinyl halide polymers and copolymers (such as polyvinyl chloride), polyvinyl ethers (such as polyvinyl methyl ether), polyvinylidene halides (such as polyvinylidene chloride), polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics (such as polystyrene), polyvinyl esters (such as polyvinyl acetate), acrylonitrile styrene copolymers, ABS resins, polyamides (such as Nylon 66 and polycaprolactam), polycarbonates, polyoxymethylenes, polyimides, polyethers, polyurethanes, rayon, rayon-tracetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, and carboxymethyl cellulose. Another type of polymer based on poly(lactic acid) that can be used includes graft copolymers, and block copolymers, such as AB block-copolymers (“diblock-copolymers”) or ABA block-copolymers (“triblock-copolymers”), or mixtures thereof. 
     Additional representative examples of polymers that may be especially well suited for use in manufacturing or coating stents include ethylene vinyl alcohol copolymer (e.g., EVOH or EVAL), poly(butyl methacrylate), poly(vinylidene fluoride-co-hexfluorapropene (e.g., SOLEF 21508, available from Solvay Solexis PVDF, Thorofare, N.J.), polyvinylidene fluoride (e.g., KYNAR, available from ATOFINA Chemicals, Philadelphia, Pa.), ethylene-vinyl acetate copolymers and polyethylene glycol. 
     Manufacturing processes for forming a bioabsorbable stent include, but are not limited to, casting, molding, extrusion, drawing or combinations thereof. Casting involves pouring a liquid polymeric composition into a mold. Molding processes include, but are not limited to, compression molding, extrusion molding, injection molding and foam molding. In compressing molding, solid polymeric materials are added to a mold and pressure and heat are applied until the polymeric material conforms to the mold. In extrusion molding, solid polymeric materials are added to a continuous melt that is forced through a die and cooled to a solid form. In injection molding, solid polymeric materials are added to a heated cylinder, softened and forced into a mold under pressure to create a solid form. In foam molding, blowing agents are used to expand and mold solid polymeric materials into a desired form, and the solid polymeric materials can be expanded to a volume in a range from about 2 to about 50 times their original volume. In the above-described molding embodiments, the solid form may require additional processing to obtain the final product in a desired form. Additional processing may include fiber processing methods such as hot drawing to induce orientation and higher crystallinity for increased mechanical strength. 
     The material for the stent can also be produced from known man-made fiber processing methods such as dry spinning, wet spinning, and melt spinning. In dry spinning, a polymer solution in warm solvent is forced through a tiny hole into warm air. The solvent evaporates into the air and the liquid stream solidifies into a continuous filament. Wet spinning method involves a polymer solution forced through tiny holes into another solution where it is coagulated into a continuous filament. Melt spinning method is a method in which a solid polymer is melted and forced through a tiny hole into cool air which solidifies the fiber into a continuous filament. 
     In some embodiments, a stent may be fabricated from a biocompatible metal or metal alloy. Representative examples include, but are not limited to, stainless steel (316L or 300), MP35N, MP2ON, Nitinol, Egiloy, tantalum, tantalum alloy, cobalt-chromium alloy, nickel-titanium alloy, platinum, iridium, platinum-iridium alloy, gold, magnesium or combinations thereof. MP35N and MP2ON are trade names for alloys of cobalt, nickel, chromium and molybdenum available from Standard Press Steel Co., Jenkintown, Pa. MP35N consists of 35 percent (%), cobalt, 35% nickel, 20% chromium and 10% molybdenum. MP2ON consists of 50% cobalt, 20% nickel, 20% chromium and 10% molybdenum. 
     In some embodiments, a treatment agent may be directly incorporated into the body of a bioabsorbable stent during the manufacturing process. For example, a treatment agent may be combined with a polymer matrix and subsequently subjected to any of the above-described manufacturing process for formation thereof. In this aspect, the treatment agent may be released in a controlled manner as the bioabsorbable stent naturally degrades in the tracheobronchial region. 
     In some applications, a polymer coating comprising at least one layer including a treatment agent can be applied to a surface of a stent for controlled release of the treatment agent. The polymer can be a polymer which exhibits a sustained-release characteristic of the treatment agent. For example, the polymer can be polyglycolide (PGA) which has a degradation rate of about 9 months to about 12 months. In another example, the polymer can be polylactide (PLA) which has a degradation rate of about 14 and about 18 months. Copolymers of PLA and PGA can also be used to tailor degradation rates. It should be appreciated that more than one coating may be applied to treat a variety of symptoms typically experienced with tracheobronchial stent placement. 
     For example, a coating can include one or a combination of the following types of layers: (a) a treatment agent layer, which may include a polymer and a treatment agent, or alternatively, a polymer-free treatment agent; (b) an optional primer layer, which may improve adhesion of subsequent layers on the stent or on a previously formed layer; (c) an optional topcoat layer, which may serve to control the rate of release of the treatment agent; and (d) an optional biocompatible finishing layer, which may improve the biocompatibility of the coating. 
     In some embodiments, the coating can be partially or completely applied to an abluminal surface or a luminal surface of the stent. The coating can be applied by methods known by those skilled in the art, including, but not limited to, dipping, spraying, pouring, brushing, spin-coating, roller coating, meniscus coating, powder coating, drop-on-demand coating, sputtering, gas-phase polymerization, solvent inversion or any combination thereof. Coating techniques are known by those skilled in the art. 
     The coating which includes a treatment agent can include, but is not limited to, an anti-inflammatory, an anti-platelet, an anti-coagulant, a fibrinolytic, an anti-thrombonic, an anti-mitotic, an anti-biotic, an anti-allergic, an anti-oxidant, an anti-proliferative and an anti-migratory. In some embodiments, the treatment agent can be an anti-inflammatory steroid or non-steroid. Examples of anti-inflammatory steroids include, but are not limited to, prednisone, oxymetholone, oxandrolone and methanodrostenolone. Examples of anti-inflammatory non-steroids (NSAID) include, but are not limited to, ibuprofen, diclofenac, diflunisal, fenoprofen, aspirin, sulindac, naproxen, indomethacin, piroxicam, ketoprofen, tolmetin and azapropazonelast. 
     The treatment agent can treat symptoms typically associated with tracheobronchial stent deployment, such as, inflammation, epithelial damage, granulation tissue formation and mucous plugging. 
     Methods of Delivery 
       FIGS. 4A-4C  illustrate an over-the-wire type stent delivery balloon catheter  400  which can be used pursuant to embodiments of the present invention. Catheter  400  generally comprises an elongated catheter shaft  402  having an outer tubular member  404  and an inner tubular member  406 . Inner tubular member  406  defines a guidewire lumen  408  adapted to slidingly receive a guidewire  410 . The coaxial relationship between outer tubular member  404  and inner tubular member  406  defines annular inflation lumen  412  (see  FIGS. 4B and 4C , illustrating transverse cross sections of the catheter  400  of  FIG. 4A , taken along lines  2 - 2  and  3 - 3  respectively). An inflatable balloon  414  is disposed on a distal section of catheter shaft  402 , having a proximal shaft section sealingly secured to the distal end of outer tubular member  404  and a distal shaft section sealingly secured to the distal end of inner tubular member  406 , so that its interior is in fluid communication with inflation lumen  412 . An adapter  416  at the proximal end of catheter shaft  402  is configured to direct inflation fluid through arm  418  into inflation lumen  412  and to provide access to guidewire lumen  408 . Balloon  414  has an inflatable working length located between tapered sections of the balloon, with an expandable stent  420  mounted on the balloon working length.  FIG. 4A  illustrates the balloon  414  in an uninflated configuration prior to deployment of the stent  420 . The distal end of catheter may be advanced to a desired region of a patient&#39;s body lumen  422  in a conventional manner, and balloon  414  inflated to expand stent  420 , seating the stent in the body lumen  422 . A stent cover  430  is on an outer surface of the stent  420 . Stent cover  430  generally comprises a tubular body, which preferably conforms to a surface of the stent and expands with the stent during implantation thereof in the patient. Although stent cover  430  is illustrated on an outer surface of the stent  430  in  FIG. 4A , the stent cover may be provided on all or part of an inner and/or an outer surface of the stent  420 . 
     It should be appreciated that, in some embodiments, a self-expanding stent may be delivered by a stent delivery catheter without (or with) a balloon. Various methods are employed for delivery and implantation of a self-expanding stent. For instance, a self-expanding stent may be positioned at the distal end of a catheter around a core lumen. Self-expanding stents are typically held in an unexpanded state during delivery using a variety of methods including sheaths or sleeves which cover all or a portion of the stent. When the stent is in its desired location of the targeted vessel the sheath or sleeve is retracted to expose the stent which then self-expands upon retraction. 
     In some methods, a stent according to the present invention may be delivered to a tracheobronchial region by a stent delivery catheter (with or without a balloon) for treatment thereof. 
     From the foregoing detailed description, it will be evident that there are a number of changes, adaptations and modifications of the present invention which come within the province of those skilled in the part. The scope of the invention includes any combination of the elements from the different species and embodiments disclosed herein, as well as subassemblies, assemblies and methods thereof. However, it is intended that all such variations not departing from the spirit of the invention be considered as within the scope thereof.