MXPA97007888A - Implante de estenosis ("stent") coated for the release of farma - Google Patents

Abstract

The description relates to a stenosis implant for implantation in a position of a body lumen of interest to a patient and includes an elastic and generally flexible tubular body having open ends and an open thin porous side wall structure and relatively thin coating layer on the tubular body that includes a biostable elastomeric material that incorporates a quantity of biologically active material dispersed therein for controlled release from the same

Description

STENOSIS IMPLANT ("STENT") COATED FOR THE LIBERATION OF DRUGS BACKGROUND OF THE INVENTION The present invention relates generally to elastic self-expanding stents (stent) for a lumen, for example, vascular, to implantation and, more particularly, to the proportion of coatings. elastomer biostable cos on such stenosis implants that incorporate biologically active species that can be eluted or diffused for controlled release directly into the coating structure. b RELATED TECHNIQUE In surgical procedure or other related invasive medical procedures, the insertion and expansion of stenosis implantation devices in blood vessels, urinary tracts or other hard-to-reach places for the purpose of avoiding restenosis, providing support or reinforcement to the wall of the Vessel or lumen and for other therapeutic or restorative functions has become a common form of long-term treatment. Normally, such prostheses are applied in an induction site using a vascular catheter, or a similar transluminal device, to lead the implant of stenosis to the site of the sites where it is released posteriorly and expands further. These devices are primarily designed as permanent implants that can be incorporated into the vascular tissue or tissue with which they come into contact when implanted. Self-expanding tubular time stenosis implant devices for translucenal implant are therefore generally known. One type of such devices includes a flexible tubular body which is comprised of several individually flexible filamentary elements, each of which extends in a spiral configuration, the center line of the body serving as a common axis. A plurality of elements are arranged which have the same winding direction but which are axially displaced with respect to each other, which are criss-crossed with a similar number of elements also displaced axially in a similar manner but which have the opposite direction of winding. This configuration provides a type of braided tubular structure that assumes a stable defined diameter in the relaxed state, but which can be reduced for insertion by applying axial tension which, in turn, produces elongation of the body with a contraction of corresponding diameter that allows that the stenosis implant is driven through the vascular system as a narrow elongated device and after that, allows the expansion to relax at the site of interest.

Prostheses of the type including a braided flexible tubular body are illustrated and described in U.S. Patents 4,655,771 and 4,954,126 to Uallsten and 5,061,275 to Uallsten et al. The general idea of using implant stenosis implanted to carry medicinal agents, such as trorbolitic agents has also been raised. US Pat. No. 5,163,952 to Froix discloses an expanding stenosis implant device which tends to recover its thermally primitive form which can be formulated to carry a medicinal agent using the material of the stenosis implant itself as a vehicle. inert polymer of the drug. Pinchuk, in U.S. Patent 5,092,877 discloses a stenosis implant of a polyrneic material that can be employed with a coating associated with drug delivery. Other patents that are directed to devices of the type using biodegradable or biosol bible polymers include Tang et al., U.S. Patent 4,916,193 and MacGregor, U.S. Patent 4,994,071. A Sahatjian patent, Patent No. 5,304. L21 describes a coating applied to a stenosis implant consisting of a hydrogel polymer and a previously selected drug in which the possible drugs include inhibitors of cell growth and hepapna. Another method for performing a coated vascular stent implant carrying a therapeutic material in which a polirnepco coating is dissolved in a solvent and the therapeutic material is dispersed in the solvent and subsequently the solvent is evaporated is described in European Patent Application 0623354 Rl, 5 published November 9, 1994. An article by Michael N. Helrnus (one of the inventors of the present invention) entitled "Medical Device Desing-R Systems Approach: Central Venous Catheters" 22nd International Society for the Hdvancernent of Material and Process Engmoering Techmcal Conference (1990) describes hepanna complexes and surfactants that are used as hepapna controlled release coatings. These polirnero / farrnaco / rneinbrana system requires two different layers of operation. Although many attempts have been made to incorporate drug release in combination with the placement of a long-term catheter or an implanted stenosis implant, for example, the associated release time has generally been relatively short, measured at hours and days, and success has been limited. There is a need for a complete technique that provides long-term drug release, i.e., over a period of weeks or months, incorporated in a controlled release system. In addition, there is an additional need with respect to incorporation JE of a drug release coating on a metal stenosis implant. Implants of polirnecic stenoses, although effective, can not match the mechanical properties of metal stenosis implants of a similar thickness. For example, to maintain an open vessel, a metal stenosis implant is superior because relatively small diameter braided stenosis implants can provide good resistance to resist circumferential pressure. For a polirnecop material to provide the same strength characteristics, a much thicker wall structure or denser filament braiding is required. In turn, this reduces the area available for flow through the stenosis implant and / or reduces the degree of porosity available in the stenosis implant. On the other hand, when applicable, it is more difficult to load said stenosis implant into the catheter delivery systems for conduction through the patient's vascular system to the site of interest. Accordingly, it is a principal object of the present invention to provide a coating on a deployed stenosis prosthesis capable of long-term release of biologically active materials. Another object of the invention is to provide a coating on the deployed stenosis prosthesis with optimum mechanical properties with a minimum surface area for the long-term release of bio-active therapeutic materials. It is still another object of the present invention to provide a coating on a deployed stenosis prosthesis using a biostable hydrophobic elastomer in which biologically active species are incorporated into the coating. Yet another object of the invention is to provide a deployed stenosis prosthesis of a siloxane polymer containing heparin crystals for dissolution through interstices of interconnected particles. In addition, a further object of the invention is to provide a braided metal deployed stenosis prosthesis having a coating of siloxane polyphenolic material containing an amount of dissolved and / or diisolated dexarnethasone. Other objects and advantages of the present invention will become apparent to those skilled in the art after becoming familiar with the specification and the appended claims.

BRIEF DESCRIPTION OF THE INVENTION Many of the limitations of the prolonged release systems of implanted prior art drugs associated with deployed stenosis prostheses are overcome by providing a relatively thin overload of biostable elastoic material, in which a quantity of biologically active material is dispersed as a coating. on the surfaces of the stenosis implant. The preferred stenosis implant is a tubular stenosis prosthesis with open ends, with a flexible, thin and porous elastic side wall. Although other materials including polyrneric materials may be used, in the preferred embodimentThe tubular body is formed by an open braid of a single or multi filament filament wire which flexes without falling and which can be deformed axially for insertion using a catheter or other similar device, but which recovers a Stable predetermined meter and length when relaxed. The coating layer is preferably applied as a mixture of polyrneric precursor and finely divided biologically active species or as a solution or partial solution of such species in the solvent or vehicle of the polymer, which hardens afterwards. The coating can be applied by bathing or spraying using solvent materials that evaporate from relatively high vapor pressure to produce the desired coating viscosity and thickness. The additional coating should be formed by adhering to the surface of the filaments of the open structure of the stenosis implant so that the open network nature of the braid structure or other pattern is retained in the coated device. The elastomeric material that forms an important constituent of the coating of the stenosis implant must possess certain properties. It is preferably a suitable biostable hydrophobic elastomeric material which does not degrade and which minimizes tissue re-entry and inflammation of the tissue and which supports encapsulation by the tissue adjacent to the implantation site of the stenosis implant. Suitable polymers for such coatings include whether for example polysiloxanes and substituted polysiloxanes, polyurethane, elastomers, plastics in general, copolymers of ethylene vinyl acetate, polyester elastomers and EPDM rubbers. The aforementioned materials are considered hydrophobic with respect to the environment contemplated by the invention. Suitable agents for incorporation include antitrornotics, anticoagulants, antiplatelet agents, trichobolites, antiproliferatives, antiplastic agents, agents that inhibit hyperplasia and in particular restenosis, inhibitors of smooth muscle cells, growth factors, inhibitors of growth factors, cell adhesion inhibitors, cell adhesion promoters and drugs that promote the formation of healthy neomrotic tissue, including endothelial cell regeneration. The positive action can come from the inhibition of particular cells (for example smooth muscle cells) or tissue formation (for example fibrornuscular tissue), while the migration of different cells (for example endothelium) and the formation is stimulated. of tissue (neoin irno tissue). Preferred materials for fabricating the braided stenosis implant include stainless steel, titanium, titanium alloys which include nitinol (an aluminum-nickel alloy material that recovers its thermal form) and certain cobalt alloys including cobalt alloys. -chrome-nickel such as Elg? loyR and PhynoxR. Additional details concerning the fabrication and details of other aspects of the stenosis implants themselves can be obtained from U.S. patents 4,655,771 and 4,954,126 to Uallsten and 5,061,275 to Uallsten et al., Supra. . As the additional information contained in the aforementioned patents is necessary for an understanding of the present invention, these are hereby incorporated by reference. S can coordinate various combinations of polyurethane coating materials with bioologically active species of interest to produce the desired effects when coated on stenosis implants to be implanted in accordance with the invention. The loads of therapeutic materials may vary. The mechanism of incorporation of the biologically active species in the surface coating and the mechanism of release depend both on the nature of the polymer of the surface coating and the material to be incorporated. The release mechanism also depends on the mode of incorporation. The material can elute paths between particles or can be administered by transport or diffusion through the encapsulation material itself. The desired release rate profile can be adapted by varying the thickness of the coating, the radial distribution of the bioactive materials, the mixing procedure, the amount of bioactive material and the density of crosslinking of the polirnecop material. The crosslink density is related to the degree of crosslinking that Place has and also to the relative rigidity of the matrix created by the particular crosslinked agent used. This, after the hardening process, determines the degree of crosslinking and thus the crosslink density of the polymeric material. For bioactive materials released from the reticulated matrix, such as hepapna, a denser lattice structure will produce a longer release time and a smaller discharge effect.

BRIEF DESCRIPTION OF THE DRAWINGS In the drawings, in which like numbers designate equal parts: FIGS. 1 and IR represent rather enlarged views of a fragment of a medical stenosis implant for use with the coating of the invention; Ll Figures 2 and 2B represent a view of a section of the stenosis implant as the drawing in Figures L and 1A when stretched or lengthened for insertion; Figure 3 is an optical microscope photograph of a configuration of the structure of a typical uncoated stenosis implant (20x magnification); Figure 4 is a scanning electron microscope (SEM) photograph of a polysiloxane coating containing heparin on a stenosis implant according to the invention (20x magnification) after releasing the heparin in a tarnpon for 49 days; Figure 4B is an enlarged scanning electron microscope (SEM) photograph of the overlay of Figure 4A (bOU magnification); Figure 5A is a scanning electron microscope photograph (SEM) of a different stenosis implant coated with a coating produced with heparma incorporated in the polysiloxane (20 magnifications); Figure 5B is an enlarged scanning electron microscope (SEM) photograph of the coating of Figure 5B (600 magnifications); Figure 6A is an optical microscope photograph (17.5 magnifications) of a histological cross section of a silicone / hepapic stenosis implant implanted in the coronary artery of a pig for 1 day; Figure 6B depicts a pair of coated filaments of the stenosis implant of Figure 6A (140x magnification) exhibiting the open porous structure of the silicone; Figure 7A is a scanning electron microscope photograph (SEM) depicting a polysiloxane coating containing 5% dexarnethasone (600 magnifications); Figure 7B represents the coating of the Figure ?? (SEM at 600 magnification) after releasing dexarnethasone in polyethylene glycol (PEG 400 / H2O) for three months; Figure 8 is a representation showing the total percentage of hepapna released over 90 days from a coated stenosis implant in which the coated layer is 50% heparin (based on the total weight of the coating) in a silicone polyacryonic matrix; the release took place in a phosphoric tarnpon (pH = 7.4) at 370C; and Figure 9 is a representation of the total percentage of dexarnethasone released over 100 days for two percentages of dexarnethasone from silicon-coated stenosis implants; the release took place in polyethylene glycol (PEG), Molecular Weight (MW) = 400 (PEG 40U / H2O, 40/60 vol / vol) at 370C.

DETAILED DESCRIPTION OF THE INVENTION A type of stenosis implant device of a kind designed to be used in combination with coatings in the present invention is schematically shown in a side view and an end view, respectively contained in Figures 1A and IB. Figure 1A shows a split section of a tubular body III, generally cylindrical, having a supporting surface formed by a series of individual filamentary elements 12, 14 and 13, 15, etc., of these elements, the elements 12 , 14, etc., generally extend in a spiral configuration displaced axially between each other, but having the central line 16 of the body 10 as a common axis. The other elements, 13, 15, displaced axially from the same shape, extend in a spiral configuration in the opposite direction, the elements extending in the two directions crossing each other in the manner indicated in Figure 1A. A tubular element so conceived and constructed can be designed to have any diameter, reminding one that increasing the desired diameter increases the number of filaments of a given diameter of wire (gauge) having a common composition and treatment above required to produce a given radiological compliance. The braided structure is easily elongated by an additional feature when applying tension at the ends axially displaced thereto with respect to one another along the center line 16 and the diameter of the device is correspondingly reduced. This is illustrated in Figures 2A and 2B in which a segment of the device 10 of Figures 1A and IB has been lengthened by moving the ends 18 and 20 apart from each other in the direction of the arrows. Once eliminated The tension on The extremes, structure 10, if not restricted by another cause, will again adopt the relaxed or unloaded configuration of Figures LA and IB. The characteristic flexibility of alar-gamient or / recovery of the stenosis implant device allows it to slide or to be screwed on a transport device while it is lengthened for conduction by the vascular system or a major internal lurnmal system of a patient to the site of Intents where this can be compressed axially and thereafter released from the transport mechanism, often a vascular catheter device. At the site of interest, it assumes an expanded state maintained on site by the friction / friction pressure between the stenosis implant and the lumen wall against which it expands. The elongation, loading, conduction and deployment of such stenosis implants is well known and need not be detailed here additionally. It is important, however, to observe that when coatings for such a stenosis implant are contemplated in the form of the present invention, an important consideration resides in the need to use a coating material which has elastic properties compatible with the properties of elastic deformation. that presents the stenosis implant that it covers. The material of the stenosis implant will be rigid and elastic but not of plastic ordo when used. As described above, Preferred materials for manufacturing the metallic braid stenosis implant include stainless steel, titanium, titanium alloys including nitol and certain cobalt and chromium alloys. The diameter of the filaments may vary - but for vascular devices up to about 10 nm in diameter, it is preferable that it ranges from 0.01 to 0.05 m. Surface coatings on stents for drug delivery according to the present invention can release drugs for a period of time from day to month and can be used, for example, to inhibit thrombus formation, inhibit migration and proliferation of smooth muscle cells, inhibit hyperplasia and restenosis and stimulate the formation of healthy neuromuscular tissue including the regeneration of endothelial cells. As such, these can be used for chronic patients after angioplasty or placement of a stenosis implant. It is also anticipated that the need for a second angioplasty procedure may be unnecessary in a significant percentage of patients in whom a repeated procedure would otherwise be necessary. A major obstacle to the successful implantation of such stenosis implants, of course, has been the appearance of thrombosis in certain arterial applications such as the placement of coronary stenosis implants. Of course, antiproliferative applications could include not only the cardiovascular ones, but any tubular vessel in which stenosis implants are placed including urological, pulmonary and endosperm gas. Various combinations of polimeric coating materials can be coordinated with the braided stenosis implant and the biologically active agent of interest to produce a combination that is compatible at the implant site and controls the release of the biologically active species over a period of time. desired time. Preferred coating polymers include silicones (polysiloxanes), polyurethanes, thermoplastic elastomers in general, copolymers of vinyl acetate or ethylene, polyolefin rubbers, EPDM rubbers and combinations thereof. Specific embodiments of the present invention include those designed to elute heparma to prevent thrombosis over a period of weeks or months and to allow diffusion or transport of dexamethasone to inhibit fibrornuscular proliferation over a similar period of time. Of course, other therapeutic substances and combinations of substances are also contemplated. The invention can be implanted in a mammalian system, such as in the human body. The hepanna elution system is preferably manufactured by making finely ground heparin crystals, preferably ground to an average particle size of less than 10 microns, and by mixing them in a liquid, the unhardened polysiloxane / dispersion material in which the mixture (polysiloxane plus hepapna) contains from less than 10% up to 80% hepapna by weight with respect to the total weight of the material and usually the empty layer from 10% to 45% hepapna. This material dissolves in the solvent and is used to coat a metallic braid stenosis implant that can be a cobalt alloy thread and as a braid, in a way that a thin and uniform coating is applied (usually 20 to 200 thick strips) of the hepanna / polymer mixture on the surfaces of the stenosis plant. The polymer is then hardened by heat, or hardened using low temperature (less than 100 ° C) thermal initiators in a room temperature vulcanization (RTV) process in situ on the stenosis implant by evaporating the solvent, usually tetrahydrofuran. (THF), the hepapna forming interparticle paths in the silicon sufficiently interconnected to allow a slow but almost complete subsequent elution.The ultra-small particle size allows the average pore size to be very small so that the elution can take place for weeks or even months A coating containing dexamethasone is produced in a somewhat different way A polysiloxane is also a preferred material A nominal amount equal to 0.4% to about 45% of the total weight of the layer is used Dexarnethasone The dexarnethasone drug is dissolved initially in a solvent, eg THF. it is in a precursor material - polysiloxane vehicle / solvent (xylene, THF, etc.) without hardening liquid. Since dexainetasone is also soluble in the solvent of the polyiloxane, it dissolves in the mixture. The coating is then applied to the stenosis implant and after application, hardening and drying, which includes the evaporation of the solvent, the dexarnethasone is dispersed in the coating layer. It is believed that the coating has a certain nature of a solid solution of recrystallized particles of dexarnethasone in silicone rubber. However, dexarnethasone, as it is a fairly small molecule does not need large pores to elute and can be transported or diffused out through the silicone material over time to release its medicinal anti-inflammatory effects. The coatings can be applied by bath coating or spray coating not even, in certain cases, by the fusion of an in situ powder form and any other technique with which the combination of polymer / biologically active agent is well adapted. icular It will be understood that a particularly important aspect of the present invention lies in the technology directed to the incorporation of very fine microparticles or suspensions of drug colorations in the polymer matrix. In the case of a crystalline drug, such as hepapine, the release of the drug is controlled by the network of drug forms in the polymer matrix, controlled the average particle size, the porosity and, thus, the speed of final elution. Figure 4A depicts a stenosis implant that has been spray coated with a solvent containing a hardened polysilicone material that includes an amount of hepapin crystals to provide a thin and uniform coating on all surfaces of the stenosis implant. The coated stenosis implant was hardened at 150 ° C for 18 minutes. The eluted sample in PBS lasted 49 days at 37 ° C and the stenotic implant was rinsed in ethanol before turning the scanning electron microscope photograph of Figure 4A. Figure 4B shows a photograph of a scanning electron microscope (SEM) much enlarged (at 600 magnifications) of a pair of the coating of Figure 4A in which the micro-porosity is evident. The thickness of the coating may vary but usually varies from about 75 to about 200 microns. Lae Figures 5A and 5B show photographs of an electron microscope with scanning of a poly iloxane stenosis implant containing hepapna. The figure shows the coating before the elution of hepapna. The coating was hardened at 150 ° C for 18 minutes. Figure 5B is a rather enlarged photograph (SEM) of a fragment of the coated surface of Figure 5A showing the surface practically non-porous prior to elution .. Figures 6A and 6B show the position of a stenosis implant according to the invention when it is implanted in the coronary of a pig. The spot shown in Figure bA represents a histological object of unknown origin. As can be seen in Figure 6B, the general texture of the silicone material containing heparma appears as a relatively open matrix containing a large number of large pores. The substantially non-porous surface of Figure 7A usually occurs with the incorporation of an amount of non-particulate material such as dexarnethasone that partially or completely dissolves in the polysiloxane solvent before coating and hardening. Once the polymer has hardened and the solvent evaporated, depending on the dexarnethasone charge, the dexamethasone reprecipitates in a hydrophobic crystalline form containing dendritic or even elongated hexagonal crystals of approximately 5 microns in size.

As can be seen in Figure 7B, even after releasing the incorporated material or after three months, the surface of the coating remains practically non-porous, indicating that the transport or diffusion of the drug outwardly through the silicone material does not require nor does it produce large pores. Dexarnethasone is incorporated in its more hydrophobic form instead of forming relatively hydrophilic salts, such as in a phosphate salt, for example. Figures 8 and 9 show representations of the total percentage of the drug released in relation to the coating layers of the long-term drug release stenosis implant. Figure 8 depicts the release of heparin from a 50% hepapin load in silicone. The silicone was hardened at 90 ° C for 16 hours. The release of hepapna takes place in a phosphoric tarnpon (pH = 7.4) for 90 days at 37 ° C. The concentration of hepanna in the phosphoric tarnpon was analyzed by Test A of Azu e. Figure 9 represents a typical analysis shown for hepapna in Figure 8, for the release of dexamethasone at two different concentrations, ie, 5% and 10% in silicone polymer. The coated stenosis implants were hardened at 150 ° C for 20 minutes and the release took place in a solution of polyethylene glycol (PEG), MW = 400 and water at 37 ° C (PEG 400 / H20) (40/60, vol. / vol). Dexarnethasone concentrations were analyzed photometrically at 241 μrn. 00 Figures 8 and 9 illustrate possible combinations of polypnepca layer and bioactive species for stenosis implants for long-term release. As described above, the rate of release profile can be altered by varying the amount of active material, the coating thickness, the radial distribution of bioactive materials, the mixing process and the crosslinking density of the polymer matrix. Considerable variation is possible so that it is possible to simulate almost any reasonable desired profile. As previously described, although the permissible load of elastomeric material with heparin can be several in the case of silicone materials, the hepapin can exceed 60% of the total weight of the layer. However, generally the most advantageous used load will range from about 10% to 45% of the total weight of the layer. In the case of dexamethaeone, the charge may be up to 50% or more of the total weight of the layer, although it preferably varies from about 0.4% to 45%. It will be noted that the mechanism of the incorporation of biologically active species into a thin surface coating structure applicable to a metal stenosis implant is an important aspect of the present invention. It eliminates the need for elongation stents implantation with relatively thick walled polymers or any membrane overlayer associated with many prior drug eluting devices, such as the need to use biodegradable or resorbable vehicles to transport the biologically active species. The technique clearly allows for long-term release and minimizes interference with the independent mechanical or therapeutic benefits of the stenosis implant itself. The coating materials are designed with a particular coating technique, contemplating the combination of coating and drug and the infusion mechanism of the drug. The consideration of the particular form- and release mechanism of the biologically active species in the coating allow the technique to produce excellent results. In this way, the release of biologically active species from the shell structure can be adjusted to suit a number of applications. Although the polymer of the coating may be any compatible biostable elastomeric material capable of adhering to the stenosis implant material as a thin layer, hydrophobic materials are preferred because it has been found that the release of the biologically active species can be controlled by Generally, it is more predictive of such materials. Preferred materials include silicone rubber elastoiners and specifically biostable brazed urethanes. This invention has been described here in great detail to suit the Patent Statutes and to provide those skilled in the art with the necessary information to apply the new principles and build and use the example embodiments when required. However, it is understood that the invention can be carried out by specifically different devices and that various modifications can be made without departing from the scope of the invention itself.

Claims (4)

1. NOVELTY OF THE INVENTION CLAIMS 1. An expandable stenosis implant for implantation in a body comprising a tubular metal body (10) having open extrusions and a side wall structure having openings in it and? n coating on a surface of said side wall structure, said coating comprises a biostable hydrophobic elastomer material which incorporates an amount of biologically active material in the same controlled release thereof, wherein said coating is continuously adjusted to said structure so as to preserve said openings when the stenosis implant is expanded.
2. 2. The stenosis implant according to claim 1, further characterized in that said tubular body (10) is formed of an open self-expanding filament braid (12, 13, 14, 15) of fine metallic thread that is axially deformable. for insertion, but which recovers a predetermined expanded diameter when relaxing.
3. 3. The stenosis implant according to claim 1, further characterized in that said coating is applied as a solvent mixture of uncured hydrophobic biostable elastomeric material and finely divided biologically active species and then cured at elevated temperature.
4. 4. The stenosis implant according to claim 1, further characterized in that said coating is applied with said fully expanded stenosis implant. 6. The stenosis implant according to claim 1, further characterized in that the coating is adapted to provide prolonged release of said biologically active material in the body. 7 - The stenosis implant according to claim 1, further characterized in that the metal is selected from the group consisting of stainless steel, titanium alloys, tantalum and cobalt and chromium alloys. 8. The stenosis implant according to claim 1, further characterized in that the biostable material is selected from the group consisting of silicones, polyurethanes, thermoplastic elastomers, copolymers of ethylene and vimlo acetate, polyolefin elastomers, EPDM rubbers and combinations thereof. 9. The stenosis implant according to claim 1, further characterized in that the biostable stornenco material is a polysiloxane and said biologically active material is selected from the group consisting of hepapne and dexarnethasone. 10. The stenosis implant according to claim 1, further characterized in that the amount of hepanna is from about 10% to about 45% of the total weight of the coating. 11. The stenosis implant according to claim 1, further characterized in that the amount of hepapin is from about 10% to about 45% of the total weight of the coating. 12. The stenosis implant according to claim 10, further characterized in that the coating is from about 20 to about 200 microns thick. 13.- Ll implant of stenosis in accordance with the r * e? Vindication 11, further characterized in that the coating is from about 30 to about 150 microns thick. 14. The stenosis implant according to claim 3, further characterized in that said biologically active species are at least partially soluble in said solvent mixture of uncured elastomeric biostatic material. 15. The stenosis implant according to claim 13, further characterized in that said biologically active material is dexarnethasone and comprises from about 0.4% to about 45% of the total weight of the coating. 16. The stenosis implant according to claim 1, further characterized in that said biologically active materials are an inhibiting agent of hyperplasia.