Patent Publication Number: US-7901728-B2

Title: Clamp mandrel fixture and a method of using the same to minimize coating defects

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is continuation of application Ser. No. 11/437,589 filed May 19, 2006, now U.S. Pat. No. 7,648,725, which is a divisional of application Ser. No. 10/319,042 filed Dec. 12, 2002, now U.S. Pat. No. 7,074,276, the contents of both applications are incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to a clamp mandrel fixture for supporting a stent during the application of a coating composition. 
     2. Description of the Background 
     Blood vessel occlusions are commonly treated by mechanically enhancing blood flow in the affected vessels, such as by employing a stent. Stents act as scaffoldings, functioning to physically hold open and, if desired, to expand the wall of the passageway. Typically stents are capable of being compressed, so that they can be inserted through small lumens via catheters, and then expanded to a larger diameter once they are at the desired location. Examples in the patent literature disclosing stents include U.S. Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued to Gianturco, and U.S. Pat. No. 4,886,062 issued to Wiktor. 
       FIG. 1  illustrates a conventional stent  10  formed from a plurality of struts  12 . The plurality of struts  12  are radially expandable and interconnected by connecting elements  14  that are disposed between adjacent struts  12 , leaving lateral gaps or openings  16  between adjacent struts  12 . Struts  12  and connecting elements  14  define a tubular stent body having an outer, tissue-contacting surface and an inner surface. 
     Stents are used not only for mechanical intervention but also as vehicles for providing biological therapy. Biological therapy can be achieved by medicating the stents. Medicated stents provide for the local administration of a therapeutic substance at the diseased site. Local delivery of a therapeutic substance is a preferred method of treatment because the substance is concentrated at a specific site and thus smaller total levels of medication can be administered in comparison to systemic dosages that often produce adverse or even toxic side effects for the patient. 
     One method of medicating a stent involves the use of a polymeric carrier coated onto the surface of the stent. A composition including a solvent, a polymer dissolved in the solvent, and a therapeutic substance dispersed in the blend is applied to the stent by immersing the stent in the composition or by spraying the composition onto the stent. The solvent is allowed to evaporate, leaving on the stent strut surfaces a coating of the polymer and the therapeutic substance impregnated in the polymer. 
     A shortcoming of the above-described method of medicating a stent is the potential for coating defects. While some coating defects can be minimized by adjusting the coating parameters, other defects occur due to the nature of the interface between the stent and the apparatus on which the stent is supported during the coating process. A high degree of surface contact between the stent and the supporting apparatus can provide regions in which the liquid composition can flow, wick, and collect as the composition is applied. As the solvent evaporates, the excess composition hardens to form excess coating at and around the contact points between the stent and the supporting apparatus. Upon the removal of the coated stent from the supporting apparatus, the excess coating may stick to the apparatus, thereby removing some of the needed coating from the stent and leaving bare areas. Alternatively, the excess coating may stick to the stent, thereby leaving excess coating as clumps or pools on the struts or webbing between the struts. 
     Thus, it is desirable to minimize the interface between the stent and the apparatus supporting the stent during the coating process to minimize coating defects. Accordingly, the present invention provides for a device for supporting a stent during the coating application process. The invention also provides for a method of coating the stent supported by the device. 
     SUMMARY 
     A device for supporting a stent during the application of a coating substance to the stent is provided. In one embodiment, the device comprises a base, a mandrel extending from the base for penetrating at least partially through the longitudinal bore of the stent, and clamp elements extending from the base, the clamp elements configured to have an open configuration for allowing the mandrel to be inserted into the longitudinal bore of the stent, and a closed configuration for securing the stent on the mandrel during the application of the coating substance to the stent. 
     The outer diameter of the mandrel can be smaller than the inner diameter of the stent. In one variation, the base can include an indented portion, wherein each of the clamp elements can include a first segment extending over the indented portion of the base and a second segment extending out from the base such that an application of a force to the first segments of the clamp elements over the indented portion of the base causes the second segments to move away from each other towards the open configuration and the release of the force results in the second segments of the clamp elements to retract back towards each other. In the closed configuration, the clamp elements can compress against the mandrel. In one embodiment, each of the clamp elements includes a first segment having a first length and a second segment having a second length, shorter than the first length, the second segments being bent in an inwardly direction towards the mandrel for engagement with the mandrel when the clamp elements are in the closed configuration. The first segments does not contact the stent when the clamp elements are in the closed configuration. Moreover, the stent should not be capable of contacting the base when the stent is secured by the clamp elements on the mandrel. 
     In accordance with another embodiment, the device comprises a mandrel capable of extending at least partially through the hollow body of a stent, and an arm element for extending through a gaped region between the struts of the stent for holding the stent on the mandrel during the application of a coating composition to the stent. In one embodiment, the device additionally includes a base member, wherein the mandrel extends from a center region of an end of the base member and the arm element extends from an edge of the end of the base member. The arm element can be characterized by a generally “L” shaped configuration having a long segment and a short segment. The long segment of the arm element can be generally parallel to the mandrel and the short segment of the arm element can be generally perpendicular to the mandrel, the short segment of the arm being configured to extend through the gaped region of the stent to compress against the mandrel. In one variation, the diameter of the mandrel plus the length of the short segment of the arm element is greater than the outer diameter of the stent so as to prevent the stent from making contact with the long segment of the arm element during the application of the coating composition. The long segment of the arm element is capable of flexibly bending for engaging and disengaging the short segment of the arm element from the mandrel. In one embodiment, in a natural position, the long segment of the arm element is in a generally linear configuration allowing the short segment of the arm element to be compressed against the mandrel. In another embodiment, the length of the mandrel as measured from the end of the base member is longer than the length of the long segment of the arm element as measured from the end of the base member. 
     In accordance with yet another embodiment of the invention, a system for supporting a stent during the application of a coating substance to the stent is provided. The system comprises a base member and a first clamp member and a second clamp member extending from the base member, wherein a segment of each clamp member is configured to penetrate into a gaped region of a scaffolding network of the stent for supporting the stent on the base member during the application of the coating substance. In one embodiment, a motor assembly is connected to the base member for rotating the stent about the longitudinal axis of the stent during the application of the coating substance. In another embodiment, a mandrel extends from the base member for being inserted through the hollow tubular body of the stent, wherein the segments of the clamp members that are configured to penetrate into the gaped regions of the scaffolding network are configured to engage with the mandrel for securing the stent on the mandrel. The system can also include a nozzle assembly for spraying the coating substance onto the stent. 
     In accordance with yet another embodiment, a device for supporting a stent during the application of a coating substance to the stent is provided, the device comprises base member having a indented portion and a clamp member having a first segment disposed on the base member and extending over the indented portion of the base member, and a second segment extending out from one end of the base member for engagement with the stent. The application of pressure on a region of the first segment extending over the indented portion of the base member causes the clamp member to extend in an outwardly direction. The device can additionally include a second clamp member having a first segment disposed on the base member and extending over the indented portion of the base member, and a second segment extending out from the one end of the base member for engagement with the stent, wherein the application of a pressure on the first segments of the first and second clamp members causes the second segments of the first and second clamp members to bias away from one another and the release of the pressure from the first segments causes the first and second clamp members to bias towards each other for engagement of the stent. 
     A method of coating a stent is also provided comprising positioning the stent on any of the embodiment of the support device and applying a coating composition to the stent. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         FIG. 1  illustrates a conventional stent. 
         FIG. 2A  illustrates a mounting assembly for supporting a stent in accordance with one embodiment of the invention. 
         FIG. 2B  illustrates an expanded perspective view of the mounting assembly in accordance with one embodiment of the present invention. 
         FIG. 3A  illustrates the clamp elements or arms of the mounting assembly in an open position in accordance with one embodiment of the present invention. 
         FIG. 3B  illustrates the clamp elements or arms of the mounting assembly in a closed position in accordance with one embodiment of the present invention. 
         FIG. 4  is a magnified view of the interface between the mounting assembly and the stent in accordance with one embodiment of the present invention. 
         FIGS. 5A-5C  are end views illustrating the interface between the mounting assembly and the stent upon rotation during the coating process in accordance with one embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     Embodiments of the Mounting Assembly 
     Referring to  FIG. 2A , a mounting assembly  18  for supporting stent  10  is illustrated to include a base  20 , a center pin or mandrel  22 , and clamp or arm elements  24 . Base  20  can connect to a motor  26 , which provides rotational motion to mounting assembly  18 , as depicted by arrow  28 , during the coating process. Another motor  30  can also be provided for moving mounting assembly  18  and thus stent  10  in a linear direction, back and forth, along a rail  32 . 
     Mandrel  22  extends longitudinally from base  20 , for example from a central region of the end of base  20 . In accordance with one embodiment, mandrel  22  and base  20  can be manufactured as a single component. Alternatively, mandrel  22  and base  20  can be manufactured separately and later coupled to one another. In such an embodiment, base  20  can include a bore  34  for receiving mandrel  22 , as illustrated in  FIG. 2B . Mandrel  22  can be press fitted into bore  34  or otherwise coupled to base  20  via, for example, welding or adhesives. In the depicted embodiment, mounting assembly  18  additionally includes a mandrel holder  36  for receiving mandrel  22 . In such an embodiment, mandrel holder  36  can be permanently or temporarily affixed within bore  34  such that surfaces  38  and  40  are flush upon assembly, and mandrel  22  can be, for example, press fit into mandrel holder  36 . A mandrel  22  manufactured separately from base  20  can also be disposable. 
     Mandrel  22  can be of any suitable diameter d m  and any suitable length l m  that will allow for sufficient support of stent  10  during the coating process. Diameter d m  should be small enough to allow maximum room for motion of stent  10 , thereby minimizing the possibility that the inner surface of stent  10  will stick to the outer surface of mandrel  22  during the coating process. Diameter d m  should be large enough to provide sufficient support to stent  10  during rotation as well as against any downward forces exerted during the spraying and drying cycles of the coating process. Length l m  should be longer than the length of stent  10  such that mandrel  22  extends beyond the mounted stent  10  at each of its opposing ends. By way of example and not limitation, mandrel  22  can have diameter d m  that is about 20% of the inner diameter of stent  10  and length l m  that is about ⅛ inch longer than the length of stent  10 . 
     Mandrel  22  can be of any material that is capable of supporting stent  10  and that is compatible with the particular coating composition to be applied to stent  10 . For example, mandrel  22  can be made of stainless steel, graphite or a composite. In another embodiment, mandrel  22  can be made of nitinol, the super-elastic properties of which allow mandrels  22  of very small diameters d m  to maintain suitable strength and flexibility throughout the coating process. 
     Mounting assembly  18  is illustrated as having two arms or clamp elements  24  spaced 180° apart and extending from the and edge of the end of the base  20 . In commercially useful embodiments, any number of arms  24  in any configuration can be used to adequately support stent  10 , and the embodiments of the present invention should not be limited to a mounting assembly  18  having two arms  24  spaced 180° apart as illustrated in the Figures. It should be noted, however, that the more arms  24  employed to support stent  10 , the more contact points that exist between mounting assembly  18  and stent  10 . In addition, although each arm  24  is depicted in the Figures as a separate component, multiple arms  24  can be formed from a single component. For example, a wire can be bent into a U-shape such that one half of the wire functions as a first arm  24  and the other half of the wire functions as a second arm  24 . 
     Each arm  24  includes an extension portion  42  extending into a support portion  44  at an angle φ 1  via an elbow  46 . Angle φ 1  can be at 90 degrees, for example. Extension portion  42  can couple arm  24  to base  20 . Arm  24  can be permanently or temporarily affixed to base  20 . Support portion  44  extends through opening  16  between struts  12  of mounted stent  10  to facilitate transient contact between mounting assembly  18  and stent  10  during the coating process. 
     Extension and support portions  42  and  44  of arms  24  can be of any suitable dimensions. Extension portion  42  should have a length l e  suitable to allow positioning of support portion  44  within a preselected opening  16  between struts  12  along mounted stent  10 . Although extension portions  42  are illustrated as having the same length l e , extension portions  42  on the same mounting assembly  18  can have different lengths l e  such that their respective support portions  44  are staggered along the length of mounted stent  10 . Length l s  of support portions  44  should be such that support tips  48  touch or compress against mandrel  22  when stent  10  is mounted thereon. Support portions  44  that are too short may cause mounted stent  10  to slip off mounting assembly  18  during the coating process, while support portions  44  that are too long run may hinder movement of stent  10  during the coating process. A diameter d e  of extension portion  42  and a diameter d s  of support portion  44  should be capable of providing sufficient support to stent  10  during rotation as well as against any downward forces exerted during the spraying and drying cycles of the coating process while allowing sufficient movement of stent  10  to prevent permanent contact points between arms  24  and stent  10 . In one embodiment, diameter d e  of extension portion  42  tapers into a smaller diameter d s  of support portion  44 , thereby optimizing both support and movement of mounted stent  10 . 
     As with mandrel  22  discussed above, arms  24  can be of any material that is capable of supporting stent  10  and that is compatible with the particular coating composition to be applied to stent  10 . The material of which arms  24  are formed should also be sufficiently flexible to allow bending into a suitable shape as well as to facilitate easy loading and unloading of stent  10 . 
     Arms  24  must be capable of opening and closing about mandrel  22  to facilitate loading and unloading of stent  10 . Arms  24  can be opened and closed in any suitable manner. For example, in one embodiment, arms  24  can be manually pulled open and pushed closed by an operator. In another embodiment, arms  24  can be opened by, for example, sliding a ring along arm  24  toward base  20  and can be closed by sliding the ring along arm  24  toward support portion  44 . 
       FIGS. 3A and 3B  illustrate an embodiment in which arms  24  function together as a clamp to facilitate opening and closing. In such an embodiment, base  20  includes an indented portion  50  over which arms  24  extend. Pinching in extension portions  42  over indented portion  50  can open arms  24 . Lip  52  further allows extension portions  42  to flexibly spread apart. When pressure is released, extension portions  42  collapse back into a pinched configuration. In this embodiment, the natural position of extension portions  42  should be generally linear and parallel to that of mandrel  22  to allow the biasing of support portion  44  on mandrel  22 . The hourglass design of base  20  depicted in the Figures allows an operator to control the opening and closing of clamp-like arms  24  with one hand. 
     Although mounting assembly  18  is illustrated such that arms  24  are attached to base  20 , arms  24  can also be attached to mandrel  22  such that base  20  is not required. In other commercially useful embodiments, mandrel  22  can be supported at its free end during the coating process in any suitable manner. Such support may help mounted stent  10  rotate more concentrically and may also help prevent a slight bend at the free end of mandrel  22  that may otherwise occur due to any downward forces exerted during the spraying and drying cycles of the coating process. In one such embodiment, the free end of mandrel  22  can be stabilized by allowing the free end to rest in a holder such as, for example, a V-block. In another embodiment, a second rotatable base can be coupled to the free end of mandrel  22 . The second base can be coupled to a second set of arms. In such an embodiment, at least one base  20  should be disengagable from mandrel  22  so as to allow loading and unloading of stent  10 . 
     Loading a Stent onto the Mounting Assembly 
     The following description is being provided by way of illustration and is not intended to limit the embodiments of mounting assembly  18 , the method of loading stent  10  onto mounting assembly  18 , or the method of using mounting assembly  18  to coat stent  10 . Referring again to  FIG. 3A , clamp-like arms  24  of mounting assembly  18  can be opened by pinching extension portions  42  of arms  24  at depression  50  in the hourglass-shaped base  20  to cause support portions  44  of arms  24  to spread apart. Stent  10  can then be loaded onto mandrel  22  by, for example, holding mounting assembly  18  at an angle (e.g., 15° from horizontal) and sliding stent  10  over mandrel  22  toward base  20 . Clamp-like arms  24  can be closed about stent  10  by releasing the pressure applied to extension portions  42 , as depicted in  FIG. 3B . 
       FIG. 4  depicts the interface between a properly mounted stent  10  and mounting assembly  18 . Support portions  44  of arms  24  should protrude through openings  16  between struts  12  of stent  10 , and support tips  48  of support portions  44  should touch or compress against mandrel  22 . As illustrated, mounted stent  10  should not touch base  20 . A gap  54  between base  20  and stent  10  should be maintained to minimize the number of contact points between mounting assembly  18  and stent  10  as well as to maximize the movement of stent  10  during rotation. By way of example and not limitation, gap  54  can be about 1 mm to about 5 mm for stent  10  that is 13 mm to 38 mm long and about 1 mm to about 9 mm for stent  10  that is about 8 mm long. Additionally, as best illustrated by the Figures, diameter d m  of mandrel plus length l s  of support portion  44  should be greater than the outer diameter of stent  10  to prevent stent  10  from contacting extension portions  42 . 
       FIGS. 5A-5C  illustrate the moving interface between a properly mounted stent  10  and mounting assembly  18  having two arms  24   a  and  24   b  spaced 180° apart upon rotation of mounting assembly  18 . As depicted in  FIG. 5A , support portions  44   a  and  44   b  of arms  24   a  and  24   b , respectively, protrude through openings  16  between struts  12  of stent  10 , and support tips  48   a  and  48   b  flush against mandrel  22 . As mandrel  22  is rotated in the direction of arrow  28 , which can be either clock-wise or counter clock-wise, mounted stent  10  also rotates in the direction of arrow  28 . As arms  24   a  and  24   b  approach the vertical position, stent  10  slides downward along support portions  44   a  and  44   b  in the direction of arrow  56 , as depicted in  FIG. 5B , until arms  24   a  and  24   b  reach the vertical position depicted in  FIG. 5C  upon rotation one half-turn or 180°. Continued rotation of mandrel  22  allows stent  10  to move back and forth along support portions  44   a  and  44   b  between elbows  46   a  and  46   b  in the direction of double arrow  58  depicted in  FIG. 5C . Such constant back and forth movement of stent  10  along support portions  44  upon rotation of mandrel  22  during the coating process allows the contact points between stent  10  and mounting assembly  18  to be transient rather than permanent, thereby preventing the coating material from flowing, wicking, collecting, and solidifying at or between arms  24  and stent  10 . In some embodiments, the back and forth motion of stent  10  along arms  24  is enhanced by downward forces exerted throughout the coating process by atomization airflow during the spraying cycle and/or dryer airflow during the drying cycle. 
     Coating a Stent Using the Mounting Assembly 
     The following method of application is being provided by way of illustration and is not intended to limit the embodiments of the present invention. A spray apparatus, such as EFD 780S spray device with VALVEMATE 7040 control system (manufactured by EFD Inc., East Providence, R.I.), can be used to apply a composition to a stent. EFD 780S spray device is an air-assisted external mixing atomizer. The composition is atomized into small droplets by air and uniformly applied to the stent surfaces. The atomization pressure can be maintained at a range of about 5 psi to about 20 psi, for example 15 psi. The droplet size depends on such factors as viscosity of the solution, surface tension of the solvent, and atomization pressure. Other types of spray applicators, including air-assisted internal mixing atomizers and ultrasonic applicators, can also be used for the application of the composition. The solution barrel pressure can be between 1 to 3.5 psi, for example 2.5 psi. The temperature of the nozzle can adjusted to a temperature other than ambient temperature during the spray process by the use of a heating block or other similar devices. For example, the temperature of the nozzle can be between 45° to about 88°, the temperature depending on a variety of factors including the type and amount of polymer, solvent and drug used. The nozzle can be positioned at any suitable distance away form the stent, for example, about 10 mm to about 19 mm. 
     During the application of the composition, mandrel  22  can be rotated about its own central longitudinal axis. Rotation of mandrel  22  can be from about 10 rpm to about 300 rpm, more narrowly from about 40 rpm to about 240 rpm. By way of example, mandrel  22  can rotate at about 100 rpm. Mandrel  22  can also be moved in a linear direction along the same axis. Mandrel  22  can be moved at about 1 mm/second to about 6 mm/second, for example about 3 mm/second, or for at least two passes, for example (i.e., back and forth past the spray nozzle). The flow rate of the solution from the spray nozzle can be from about 0.01 mg/second to about 1.0 mg/second, more narrowly about 0.1 mg/second. Multiple repetitions for applying the composition can be performed, wherein each repetition can be, for example, about 1 second to about 10 seconds in duration. The amount of coating applied by each repetition can be about 0.1 micrograms/cm 2  (of stent surface) to about 40 micrograms/cm 2 , for example less than about 2 micrograms/cm 2  per 5-second spray. 
     Each repetition can be followed by removal of a significant amount of the solvent(s). Depending on the volatility of the particular solvent employed, the solvent can evaporate essentially upon contact with the stent. Alternatively, removal of the solvent can be induced by baking the stent in an oven at a mild temperature (e.g., 60° C.) for a suitable duration of time (e.g., 2-4 hours) or by the application of warm air. The application of warm air between each repetition prevents coating defects and minimizes interaction between the active agent and the solvent. The temperature of the warm air can be from about 30° C. to about 85° C., more narrowly from about 40° C. to about 55° C. The flow rate of the warm air can be from about 20 cubic feet/minute (CFM) (0.57 cubic meters/minute (CMM)) to about 80 CFM (2.27 CMM), more narrowly about 30 CFM (0.85 CMM) to about 40 CFM (1.13 CMM). The blower pressure can be, for example between 10 to 35 psi, more narrowly 12 to 15 psi and can be positioned at a distance of about 10 to 20 mm away from the stent. The warm air can be applied for about 3 seconds to about 60 seconds, more narrowly for about 10 seconds to about 20 seconds. By way of example, warm air applications can be performed at a temperature of about 50° C., at a flow rate of about 40 CFM, and for about 10 seconds. Any suitable number of repetitions of applying the composition followed by removing the solvent(s) can be performed to form a coating of a desired thickness or weight. Excessive application of the polymer in a single application can, however, cause coating defects. 
     Operations such as wiping, centrifugation, or other web clearing acts can also be performed to achieve a more uniform coating. Briefly, wiping refers to the physical removal of excess coating from the surface of the stent; and centrifugation refers to rapid rotation of the stent about an axis of rotation. The excess coating can also be vacuumed off of the surface of the stent. 
     In accordance with one embodiment, the stent can be at least partially pre-expanded prior to the application of the composition. For example, the stent can be radially expanded about 20% to about 60%, more narrowly about 27% to about 55%—the measurement being taken from the stent&#39;s inner diameter at an expanded position as compared to the inner diameter at the unexpanded position. The expansion of the stent, for increasing the interspace between the stent struts during the application of the composition, can further prevent “cob web” formation between the stent struts. 
     In accordance with one embodiment, the composition can include a solvent and a polymer dissolved in the solvent. The composition can also include active agents, radiopaque elements, or radioactive isotopes. Representative examples of polymers that can be used to coat a stent include ethylene vinyl alcohol copolymer (commonly known by the generic name EVOH or by the trade name EVAL), poly(hydroxyvalerate); poly(L-lactic acid); polycaprolactone; poly(lactide-co-glycolide); poly(hydroxybutyrate); poly(hydroxybutyrate-co-valerate); polydioxanone; polyorthoester; polyanhydride; poly(glycolic acid); poly(D,L-lactic acid); poly(glycolic acid-co-trimethylene carbonate); polyphosphoester; polyphosphoester urethane; poly(amino acids); cyanoacrylates; poly(trimethylene carbonate); poly(iminocarbonate); copoly(ether-esters) (e.g. PEO/PLA); polyalkylene oxalates; 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; vinyl halide polymers and copolymers, such as polyvinyl chloride; polyvinyl ethers, such as polyvinyl methyl ether; polyvinylidene halides, such as polyvinylidene fluoride and polyvinylidene chloride; polyacrylonitrile; polyvinyl ketones; polyvinyl aromatics, such as polystyrene; polyvinyl esters, such as polyvinyl acetate; copolymers of vinyl monomers with each other and olefins, such as ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl acetate copolymers; polyamides, such as Nylon 66 and polycaprolactam; alkyd resins; polycarbonates; polyoxymethylenes; polyimides; polyethers; epoxy resins; polyurethanes; rayon; rayon-triacetate; cellulose; cellulose acetate; cellulose butyrate; cellulose acetate butyrate; cellophane; cellulose nitrate; cellulose propionate; cellulose ethers; and carboxymethyl cellulose. 
     “Solvent” is defined as a liquid substance or composition that is compatible with the polymer and is capable of dissolving the polymer at the concentration desired in the composition. Examples of solvents include, but are not limited to, dimethylsulfoxide (DMSO), chloroform, acetone, water (buffered saline), xylene, methanol, ethanol, 1-propanol, tetrahydrofuran, 1-butanone, dimethylformamide, dimethylacetamide, cyclohexanone, ethyl acetate, methylethylketone, propylene glycol monomethylether, isopropanol, isopropanol admixed with water, N-methyl pyrrolidinone, toluene, and combinations thereof. 
     The active agent can be for inhibiting the activity of vascular smooth muscle cells. More specifically, the active agent can be aimed at inhibiting abnormal or inappropriate migration and/or proliferation of smooth muscle cells for the inhibition of restenosis. The active agent can also include any substance capable of exerting a therapeutic or prophylactic effect in the practice of the present invention. For example, the agent can be for enhancing wound healing in a vascular site or improving the structural and elastic properties of the vascular site. Examples of agents include antiproliferative substances such as actinomycin D, or derivatives and analogs thereof (manufactured by Sigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee, Wis. 53233; or COSMEGEN available from Merck). Synonyms of actinomycin D include dactinomycin, actinomycin IV, actinomycin I 1 , actinomycin X 1 , and actinomycin C 1 . The active agent can also fall under the genus of antineoplastic, antiinflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antibiotic, antiallergic and antioxidant substances. Examples of such antineoplastics and/or antimitotics include paclitaxel (e.g. TAXOL® by Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g. Taxotere® , from Aventis S.A., Frankfurt, Germany) methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g. Adriamycin® from Pharmacia &amp; Upjohn, Peapack N.J.), and mitomycin (e.g. Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of such antiplatelets, anticoagulants, antifibrin, and antithrombins include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, and thrombin inhibitors such as Angiomax™ (Biogen, Inc., Cambridge, Mass.). Examples of such cytostatic or antiproliferative agents include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g. Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g. Prinivil® and Prinzide® from Merck &amp; Co., Inc., Whitehouse Station, N.J.); calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacor® from Merck &amp; Co., Inc., Whitehouse Station, N.J.), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), and nitric oxide. An example of an antiallergic agent is permirolast potassium. Other therapeutic substances or agents that may be appropriate include alpha-interferon, genetically engineered epithelial cells, rapamycin and dexamethasone. Exposure of the active ingredient to the composition should not adversely alter the active ingredient&#39;s composition or characteristic. Accordingly, the particular active ingredient is selected for compatibility with the solvent or blended polymer-solvent. 
     While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects. Therefore, the appended claims are to encompass within their scope all such changes and modifications as fall within the true spirit and scope of this invention.