Abstract:
A method for producing an agent depot for mechanical connection to a surface of an endovascular implantable body, comprising a) providing one or more polymers; b) providing one or more agents; and c) producing an agent depot from said polymers and said agents, the agent depot being mechanically connectable to the surface of the body using force action or adhesive.

Description:
FIELD 
       [0001]    The present disclosure relates to a method for producing an agent depot for an implantable body such as an endovascular stent; a method for producing an agent-coated endovascular implantable body; an agent-charged endovascular implantable body, producible according to the method; and, a kit comprising one or more agent depots, producible according to a method, and one or more endovascular implantable bodies. 
       BACKGROUND 
       [0002]    Endovascular implantable bodies are used in medical technology, inter alia, for supporting vascular structures. In particular, endovascular prostheses and/or implants, in particular, endovascular stents, are used to treat coronary heart disease, in particular, acute myocardial infarction. Such bodies are also known for the treatment of aneurysms. Stents fundamentally have a support structure which is capable of supporting the wall of a vessel and widening the vessel and/or bypassing an aneurysm. 
         [0003]    For this purpose, stents are inserted in a compressed state into the vessel and then expanded at the location to be treated and pressed against the vascular wall. This expansion may be performed with the aid of a balloon catheter, for example. Alternatively, self-expanding stents are also known. These are constructed from a superelastic metal, such as Nitinol. 
         [0004]    However, extremely small injuries and cracks (dissections) arise in the vascular wall with the expansion of the blood vessel, which frequently heal without problems, but may result in approximately one-third of the cases in growths (proliferation) and finally in renewed vascular constriction (restenosis) due to the triggered cell growth. The expansion of the vessel by endovascular stents additionally does not remove the causes of the original stenosis, i.e., the molecular pathological changes in the vascular wall. One cause of restenosis is also the excess elasticity of the blood vessels stretched by the stent. The stretched blood vessel typically constricts excessively after removal of the balloon, so that the vascular cross-section is decreased in relation to the area of the blood vessel which was not stretched (obstruction, so-called negative remodeling). The latter effect may be avoided by the placement of an endovascular implant, typically a stent. 
         [0005]    The introduction of stents into interventional treatment of stable and unstable angina pectoris in coronary heart diseases has resulted in a significant reduction of the rate of restenosis and thus in better long-term results, which is primarily to be attributed to the lumen acquisition, however, the extremely small injuries which occur, which may induce the proliferation, may in turn trigger a restenosis. In addition, the presence of a foreign body of this type in the vascular system may initiate a cascade of cellular molecular processes, which may result in a gradual overgrowth of the vessel (in particular also thrombosis) in the area in which the implant, in particular the stent, is implanted. 
         [0006]    For some years, attempts have therefore been made to reduce the danger of restenosis upon the implantation of stents further by using stents coated with agents (local drug delivery (LDD); drug eluting stents (DES)). However, agent carriers which are implanted in vessels are also used in illnesses which are not coronary-related (drug reservoirs for non-coronary applications (cancer treatment, etc.)). 
         [0007]    The carriers of agent-containing coating systems of this type typically consist of a biocompatible material which is either of natural origin or may be obtained synthetically. Numerous methods have been developed for applying the coating systems to the stent, such as rotation pulverization methods, immersion methods, and spraying methods. The coating system at least regionally covers the surface of the stent, a release of the pharmacological agent into the human or animal body occurring through gradual degradation of the carrier and/or diffusion into the surrounding tissue. 
         [0008]    An agent-containing coating of endovascular stents is typically to be understood as a flat coating. However, the coatings may also partially comprise the existing holes and/or cavities of the stent geometry being filled or single-sided or punctual coatings existing on the support structure of the stent. Such coatings are, however, very technologically demanding and also time-consuming and costly. It has now been established that not all coating materials may be coated with and without incorporated agent(s) directly on the implantable body according to the typically used methods. 
         [0009]    In general, in most coating methods prior dissolving of the polymer matrix is necessary before the coating. However, to ensure the necessary freedom from solvent of the “drug eluting” implant, sometimes complex method steps must be performed to extract the same solvent, which are performed after the coating step. 
         [0010]    Because of differing physical-chemical properties of substrate surface and coating material (hydrophobic, hydrophilic properties), the desired surface properties of the implant to be produced may possibly not be achieved. To still achieve these properties, though, sometimes complex method steps are required for pretreating the particular surface, which may possibly also have consequences for the biocompatibility because of an additional manufacturing step. 
         [0011]    Agent-charged polymer layers having a high agent charge may also in particular result in mechanical problems of the layer upon the dilation of the stent. 
         [0012]    In the known coating forms of stents, one is typically restricted to one agent-dose combination, because it is very difficult to implement coatings which have different elution rates of an agent or elutions of multiple agents (multiple drug release, in particular dual-drug release, triple-drug release, etc.), in particular at different elution rates. 
       SUMMARY 
       [0013]    The present disclosure describes several exemplary embodiments of the present invention. 
         [0014]    One aspect of the present disclosure provides a method for producing an agent depot for mechanical connection to a surface of an endovascular implantable body, comprising a) providing one or more polymers; b) providing one or more agents; and c) producing an agent depot from said polymers and said agents, the agent depot being mechanically connectable to the surface of the body using either force action or adhesive. 
         [0015]    Another aspect of the present disclosure provides a method for producing an agent-charged endovascular implantable body, comprising the steps of a) providing an endovascular implantable body; b) providing one or more different agent depots which are produced by (i) providing one or more polymers; (ii) providing one or more agents; and (iii) producing an agent depot from the polymers and the agents, the agent depot is mechanically connectable to the surface of the body using either force action or adhesive; and c) mechanically connecting one of said agent depots to said body. 
         [0016]    A further aspect of the present disclosure provides an agent-charged, endovascular implantable body, said body produced according to a method, comprising a) providing an endovascular implantable body; b) providing one or more different agent depots produced by (i) providing one or more polymers, (ii) providing one or more agents, and (iii) producing an agent depot from the polymers and the agents, the agent depot is mechanically connectable to the surface of the body using either force action or adhesive; and c) mechanically connecting one of said agent depots to said body. 
         [0017]    An additional aspect of the present disclosure provides a kit, comprising a) one or more agent depots, said agent depots produced by providing one or more polymers, providing one or more agents, and producing an agent depot from the polymers and the agents, the agent depot being implemented in such a manner that the agent depot is mechanically connectable to the surface of the body using either force action or adhesive; and b) one or more endovascular implantable bodies. 
         [0018]    Another aspect of the present disclosure provides a method for producing an agent-charged, endovascular implantable body for prophylaxis or treatment of a stenosis, an aneurysm, or a tumor tissue in a human or animal body, the agent depots being produced by providing one or more polymers, providing one or more agents, and producing an agent depot from the polymers and the agents, the agent depot being implemented in such a manner that the agent depot is mechanically connectable to the surface of the body using either force action or adhesive. 
         [0019]    Yet another aspect of the present disclosure provides a method for prophylaxis or treatment of a stenosis, an aneurysm, or a tumor tissue of a human or animal body, comprising a) providing an endovascular implantable body; b) providing one or more different agent depots, said agent depots produced by providing one or more polymers; providing one or more agents; and producing an agent depot from the polymers and the agents, the agent depot being implemented in such a manner that the agent depot is mechanically connectable to the surface of the body using either force action or adhesive; c) mechanically connecting one of said agent depots to said body; and d) implanting the agent-charged body produced in step c) in a blood vessel which carries blood to the tumor tissue. 
         [0020]    One feature of the present disclosure provides an agent depot which may be bound to an endovascular implantable body, independently of its material. A further feature of the present disclosure provides an endovascular implantable body which comprises one or more agent depots having one or more agents, the agents being adjustably targeted to the elution time and concentration. A further feature addresses reduction of undesired implant side effects, e.g., increase of the restenosis and/or thrombosis risk. 
         [0021]    The present invention is based on the finding that an agent depot according to the present disclosure, which may be manufactured separately from the actual endovascular implantable body, may be optimized in a technologically simpler manner in regard to the elution characteristic of the incorporated agents on one hand and may be directly mechanically connected to the implantable body, preferably the stent, independently of the material used on the other hand. Therefore, the agent depots produced according to the present disclosure, are mechanically connected to the endovascular implantable body, preferably in a form-fitting manner 
         [0022]    Accordingly, advantages of an implantable body produced according to the present disclosure having agent depots according to the present disclosure are particularly that as a result of the technological separation of the production of the implantable body and of the agent depot, a direct agent charge of the implantable body is made possible independently of the material of the implantable body. 
         [0023]    A further feature is that a charge of an implantable body produced according to the present disclosure with one or more agent depots according to the present disclosure allows a flexible agent therapy of the implantable body custom tailored for the particular illness. A charge of an implant with one or more agent depots according to the present disclosure is technologically simple and already existing endovascular implantable bodies, whether or not they are agent-coated, may also be charged using the agent depots according to the present disclosure. In particular, different numbers of agent depots may also be charged in different spatial areas of the endovascular implantable body, preferably the stent. Exemplary embodiments are shown in  FIGS. 2   a  and  2   b.  Such exemplary embodiments may be advantageous, in particular, if an individual agent treatment custom-tailored to a patient is necessary. In this case, the attending physician may perform the custom-tailored charging of an endovascular implantable body, preferably a stent, himself. 
         [0024]    A further feature of the present disclosure is that not only one, but rather also multiple agents may be provided in the agent depot, in particular, in different doses, which, because of the limitation due to the layer thickness, may not be achieved using typical coatings of implantable bodies. 
         [0025]    In particular, chronologically graduated elution curves of one or more agents may be implemented in the agent depot, for example, a continuous increase of one or more agents to accustom the body in which the implant having the agent depot is implanted to the agents step by step. 
         [0026]    In typical agent-coated stents, charges of greater than 70% agent result in poor mechanical properties, in particular, in breaking off of the agent layer as well as often very short elution kinetics which are not always desirable. 
         [0027]    Because of the typical layer thicknesses of 50 to 100 μm, stent geometries may arise which occupy an amount of volume of the vascular lumen which may result in problems during the implantation of the stent (deliverability) upon passage of stenoses or other constrictions (large “crossing profile”). 
         [0028]    In contrast to the typical coating methods, the use of agent depots according to the present disclosure, which are preferably clipped onto a body to be implanted, preferably a stent, allows the exploitation of the space between the struts and/or webs of the stent to be implanted or the clipping of the agent depot on the end of the body to be implanted, in particular, the stent. Especially with terminal clipping, agent depots which may comprise a high concentration of one or more agents may be used. 
         [0029]    High agent concentrations are particularly advantageous for agents from the group consisting of limus agents for treating restenosis, in particular, comprising sirolimus (rapamycin), zotarolimus (Abt-578), tacrolimus (Fk506), everolimus, biolimus, in particular, biolimus A9, paclitaxel (taxol), pimecrolimus, lipid regulators, preferably fibrates, immunosuppressants, vasodilatators, preferably sartane, calcium channel blockers, calcineurin inhibitors, preferably tacrolimus, antiphlogistics, preferably cortisone and diclofenac, anti-inflammatory agents, preferably imidazole, antiallergens, oligonucleotides, preferably decoy oligodeoxynucleotide (dODN), estrogens, preferably genistein, endothelial producers, preferably fibrin, steroids, proteins/peptides, proliferation inhibitors, analgesics, antirheumatic agents, and the like. 
         [0030]    Higher agent concentrations may also be desirable for local cancer treatments, so that the agents from the group of cytostatics, if the implant is placed in a vessel supplying the tumor tissue, preferably in proximity to the tumor tissue, may be released directly into the blood vessel there and may be supplied at high concentration directly using the bloodstream to the tumor tissue. The possibility exists that side effects which are associated with the cytostatics used may be reduced. 
         [0031]    Exemplary embodiments according to the present disclosure for the preferred features described above are shown as examples in  FIGS. 3   a  and  5   a.    
         [0032]    A further feature of the present disclosure is that multiple agent depots which each comprise different agents may be connected to one endovascular implantable body and thus a multiple drug release (release of multiple agents), in particular, a dual-drug release (release of two agents) or a triple-drug release (release of three agents) may be achieved which may hardly be achieved technologically or may only be achieved at increased cost and/or time consumption by a typical coating method. An example of such a design according to the present disclosure is described in  FIG. 2   a.    
         [0033]    A further feature of the present disclosure is that interactions between the agents used and the material used for the implantable body, preferably a stent, may be reduced. This is implemented, in particular, in that the endovascular implantable body, preferably a stent, is produced separately from the agent depot according to the present disclosure. This is useful, in particular, if degradable (main) bodies are employed, such as degradable stents, in particular, degradable metal stents, because a direct agent coating with the (main) body is possible only with difficulty or sometimes not at all using typical methods due to the interaction with the material of the body. The terminal linkage of one or more agent depots on degradable main bodies is more preferable because the distance between the mutually influencing materials is increased and thus the mutual influence may be reduced. 
         [0034]    The preferred designs of the features according to the present disclosure are described hereinafter and in the claims and may also be understood from the description of the figures and the associated figures. The preferred designs relate to all features of the present disclosure even if no express reference thereto is disclosed. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0035]    Various aspects of the present disclosure are described hereinbelow with reference to the accompanying figures. The figures show exemplary details of the abluminal surface of stent geometries of a stent main body and/or the agent depot according to the present disclosure in a perspective view or in cross-section. However, the present disclosure is not restricted to the stent geometries shown here and/or to the configuration of the agent depot shown. 
           [0036]      FIG. 1   a  is a top view of an abluminal detail of a stent geometry  2  having multiple agent depots  1  in bead form  11 ; 
           [0037]      FIG. 1   b  is a perspective view of a slotted agent depot in bead form  11 ; 
           [0038]      FIG. 2   a  is a top view of an abluminal detail of a stent geometry  2  having multiple agent depots  1  in sleeve form  12 . 
           [0039]      FIG. 2   b  is a top view of an abluminal detail of a stent geometry  2  having multiple agent depots  1  in sleeve form  12  having varying charge of agent depots over the longitudinal axis; 
           [0040]      FIG. 2   c  is a perspective view of a slotted agent depot in sleeve form  12 ; 
           [0041]      FIG. 3   a  is a top view of an abluminal detail of the stent geometry  2  having multiple flat slotted agent depots  1 ,  13  clipped onto struts; 
           [0042]      FIG. 3   b  is a perspective view of a flat slotted agent depot  13 ; 
           [0043]      FIG. 4   a  is a top view of an abluminal detail of a stent geometry  2  having multiple agent depots  1 ,  14 , and  15 , which are clipped onto the abluminal surface on struts; 
           [0044]      FIG. 4   b  is a perspective view of an agent depot  14 ; 
           [0045]      FIG. 4   c  is a perspective view of an agent depot  15 ; 
           [0046]      FIG. 4   d  is a top view of an abluminal detail of a stent geometry  2  having multiple agent depots  1  in slotted preform  16 ; 
           [0047]      FIG. 4   e  is a perspective view of an agent depot  16 ; 
           [0048]      FIG. 5   a  is a top view of an abluminal detail of a stent geometry  2  having terminal agent depot  1  in the form of a clipped-on strip  17  or body  18 ; 
           [0049]      FIG. 5   b  is a perspective view of an agent depot in strip form  17 ; 
           [0050]      FIG. 5   c  is a cross-section view of an agent depot in the form of a body  18 ; 
           [0051]      FIG. 6   a  is a top view of an abluminal detail of a stent geometry  2  having multiple agent depots  1 ,  19 , which are attached to the terminal arcs of the webs of the stent  2 ; 
           [0052]      FIG. 6   b  is a perspective view of an agent depot  19  in preform; 
           [0053]      FIG. 7   a  is a schematic view of how an agent depot  1  is glued onto a stent strut  22  of a stent  2 ; 
           [0054]      FIG. 7   b  is a cross-section view of a stent strut  22  having glued-on agent depot  1 ; 
           [0055]      FIG. 7   c  is a cross-section view of a stent strut  22  having abluminal glued-on agent depot  1 ; 
           [0056]      FIG. 7   d  is a cross-section view of a stent strut  22  having abluminal glued-on agent depot  1 ; 
           [0057]      FIG. 8   a  is a cross-section view of a stent strut  22  having an agent depot  1  having connection mechanism  3 ; 
           [0058]      FIG. 8   b  is a schematic view of the connection mechanism  31  of the agent depot  1 ; 
           [0059]      FIG. 8   c  is a schematic view of the connection mechanism  32  of the agent depot  1 ; 
           [0060]      FIG. 8   d  is a schematic view of the connection mechanism  33  of the agent depot  1 ; 
           [0061]      FIG. 8   e  is a schematic view of the connection mechanism  34  of the agent depot  1 ; 
           [0062]      FIG. 9   a  is a cross-section view of a stent strut  22  having agent depot  1  and overlap area  4 ; 
           [0063]      FIG. 9   b  is a cross-section view of agent reservoir  5 , which is situated on the abluminal side; 
           [0064]      FIG. 9   c  is a schematic view of the agent reservoir  5 ; 
           [0065]      FIG. 9   d  is a schematic view of the agent reservoir  5 ; and 
           [0066]      FIG. 9   e  is a schematic view of the agent reservoir  5 . 
       
    
    
       [0067]    For purposes of the present disclosure, an implantable body typically represents, on one hand, a degradable or nondegradable, cardiovascular or peripheral stent as well as a stent for other cavities, such as the esophagus, the gall duct, the urethra, the prostate, or the trachea. On the other hand, implantable bodies, for purposes of the present disclosure, may represent local drug delivery implants which are implanted endovascularly in the blood vessels or other cavities. Furthermore, implantable bodies may represent neuroapplications as well as subcutaneous applications for continuous agent release (such as hormone preparations), as well as stimulation electrons or regional drug delivery applications. 
         [0068]    For purposes of the present disclosure, degradable bodies, preferably stents, comprise degradable metal or degradable polymer as materials. 
         [0069]    Degradable Metal Material: 
         [0070]    The degradable metallic material is preferably a biocorrodible alloy, selected from the group consisting of magnesium, iron, zinc, and tungsten; in particular, the degradable metallic material is a magnesium alloy. 
         [0071]    The alloy, in particular, comprising magnesium, iron, zinc, and/or tungsten, is to be selected in composition so that the alloy is biocorrodible. For purposes of the present disclosure, alloys are considered to be biocorrodible when degradation occurs in physiological surroundings which finally results in the entire stent or the part of the stent formed from the material losing its mechanical integrity. For purposes of the present disclosure, an alloy is a metallic structure whose main component is magnesium, iron, zinc, or tungsten. For purposes of the present disclosure, the main component is the alloy component whose weight proportion in the alloy is highest. A proportion of the main component is preferably more than 50 wt.-%, more preferably more than 70 wt.-%. 
         [0072]    If the material is a magnesium alloy, the material preferably contains yttrium and rare earth metals because an alloy of this type is distinguished due to its physiochemical properties and high biocompatibility, in particular, also its degradation products. 
         [0073]    Alloys of the WE series (WE43, and the like) as well as magnesium alloys of the composition rare earth metals 5.2 to 9.9 wt.-%, thereof yttrium 0.0 to 5.5 wt.-%, and the remainder comprising zircon less than 1 wt.-% are especially preferable, magnesium making up the proportion of the alloy to 100 wt.-%. These magnesium alloys have already confirmed their special suitability experimentally and in initial clinical trials, i.e., the magnesium alloys display a high biocompatibility, favorable processing properties, good mechanical characteristics, and corrosion behavior adequate for the intended uses. For purposes of the present disclosure, the collective term “rare earth metals” includes scandium (21), yttrium (39), lanthanum (57) and the 14 elements following lanthanum (57), namely cerium (58), praseodymium (59), neodymium (60), promethium (61), samarium (62), europium (63), gadolinium (64), terbium (65), dysprosium (66), holmium (67), erbium (68), thulium (69), ytterbium (70) und lutetium (71). 
         [0074]    In particular, if agent depots according to the present disclosure are connected to magnesium stents, undesired interactions of the acid-degradable polymer agent depot and the basic-degrading magnesium stent, in particular, the acceleration of the magnesium corrosion and thus a more rapid loss of the stent collapsing pressure resulting therefrom, may be reduced because of the spatial distance. The degradation of the polymer in the agent depot may also be slowed by the increased spatial distance, because of which less irritation of the tissue occurs and the polymer layer does not peel off of the implanted stent. 
         [0075]    Degradable Polymer Body: 
         [0076]    Bodies, particularly stents made of degradable polymers, preferably comprise polydioxanone; polyglycolide; polycaprolactone; polylactides, preferably poly-L-lactide, poly-D,L-lactide, and polymers and blends thereof, such as poly(L-lactide-co-glycolide), poly(D,L-lactide-co-glycolide), poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-trimethylene carbonate), and triblock copolymers; polysaccharides, preferably chitosan, levan, hyaluronic acid, heparin, dextran, and cellulose; polyhydroxyvalerate; ethylvinylacetate; polyethylene oxide; polyphosphorylcholine; fibrin; albumin, and the like. 
         [0077]    If endovascular implantable stents are used as the implantable bodies for purposes of the present disclosure, all typical stent geometries may be used. Stent geometries which are described in U.S. Pat. No. 6,896,695; U.S. Patent Publication No. 2006/241742; U.S. Pat. No. 5,968,083; European Patent Application No. 1 430 854; U.S. Pat. No. 6,197,047; and European Patent Application No. 0 884 985 are particularly preferred. 
         [0078]    If stents are used as the endovascular implantable bodies, the agent depots are preferably mechanically connected to the stent after the stent is crimped on a catheter to be used. This sequence has the advantage that the agent depots are not impaired in their matrix by the procedure of crimping. 
         [0079]    The mechanical connection of the agent depot produced according to the present disclosure to the endovascular implantable body, preferably an endovascular stent, may preferably be designed as form-fitting with a web or strut of the stent. Preferably using a C-shaped gripper, which preferably clips the agent depot to the implantable body, preferably a stent, in a form-fitting manner. Such a design according to the present disclosure is shown, for example, in  FIGS. 1   b,    2   c,    3   b,    4   c,    4   e,    5   b,  and  5   c.  However, all other fastening measures of the stent according to the present disclosure which one skilled in the art considers because of his experience in the art are hereby also claimed. These include, in particular, embodiments in hook form, which are shown as examples in  FIG. 4   b.  Suitable agent depots may also be shrunk onto the endovascular implantable body, preferably stent, or parts thereof, as shown in  FIGS. 6   a  and  6   b.    
         [0080]    Agent depots according to the present disclosure may also be glued onto an implantable body, preferably a stent, as shown in, for example, in  FIGS. 7   a - 7   d.  According to the present disclosure, suitable agent depots preferably have concave points which cling to the struts of an implantable stent. Instant adhesives from the group consisting of acrylates, fibrin adhesives, fats, and polysaccharides are preferably suitable as the adhesive. 
         [0081]    Agent depots which completely enclose a strut of a stent and are suitably connected to one another such that the agent depot may not unroll from the strut are also conceivable (see  FIGS. 8   a  through  8   e ). 
         [0082]    One or more agent depots, which possibly differ in the agent concentration and/or in the type of agent, may be clipped on each implantable body, preferably a stent. The agent depots are typically designed so that they interfere in a vascular system as little as possible upon implantation of the body and are, therefore, housed in existing intermediate spaces of the implantable body, preferably a stent, or are pulled over the body, preferably a stent, as thin, compact sleeves. In a further exemplary embodiment, only the abluminal surface of an agent-charged body according to the present disclosure, preferably a stent, has the agent depot, in particular, the component of the agent depot which is coated with agent. 
         [0083]    The polymers of the agent depot preferably include: nondegradable polymers: polyethylene; polyvinylchloride; polyacrylates; preferably polyethyl- and polymethylacrylates, polymethylmethacrylate, polymethyl-co-ethyl-acrylate, and ethylene/ethylacrylate; polytetrafluoroethylene, preferably ethylene/chlorotrifluoroethylene copolymers, ethylene/tetrafluoroethylene copolymers; polyamides, preferably polyamide imide, PA-11, PA-12, PA-46, PA-66; polyetherimide; polyethersulfone; poly(iso)butylene; polyvinylchloride; polyvinylfluoride; polyvinylalcohol; polyuretliane; polybutylene terephthalate; silicones; polyphosphazene; polymer foams, preferably polymer foams made of carbonates, styrenes; copolymers and/or blends of the above-listed polymer classes, polymers of the class of thermoplastics, and degradable polymers: polydioxanone; polyglycolide; polycaprolactone; polylactides, preferably poly-L-lactide, poly-D,L-lactide, and copolymers and blends thereof, preferably poly(L-lactide-co-glycolide), poly(D,L-lactide-co-glycolide), poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-trimethylene carbonate); triblock copolymers; polysaccharides, preferably chitosan, levan, hyaluronic acid, heparin, dextran, cellulose; polyhydroxyvalerate; ethylvinylacetate; polyethylene oxide; polyphosphorylcholine; fibrin; albumin; polyhydroxy butyric acid, preferably atactic, isotactic, and/or syndiotactic polyhydroxy butyric acid and their blends. 
         [0084]    An agent depot produced according to the present disclosure is preferably produced in sleeve form (see  FIGS. 2   c  and  4   c,  for example), film form (see  FIG. 5   b,  for example), preform (see  FIGS. 1   b,    3   b,    4   b,    4   e,  and  5   c,  for example), or as a relatively rigid net. For purposes of the present disclosure, the term “sleeve” refers to a possibly flexible molded body which is round or oval in cross-section and is open on two sides. For purposes of the present disclosure, the term “preform” describes a negative shape of a point of the implant to which it is later attached. This “preform” may be flexible or rigid. 
         [0085]    If an agent depot produced according to the present disclosure in sleeve form is used, the agent depot is preferably produced using a pure extrusion method, blow-molding method, or deep-drawing process. In rare cases, however, the agent depot is also produced by joining or gluing technology. For purposes of the present disclosure, joining technology, in the case of the sleeve, is defined as shrinking or joining “to fit” by pushing on, for example. If the sleeve only represents an intermediate step in the production of the medication carrier, the sleeve may also be slotted, lined on the interior with a bonding agent, and finally connected to the stent, e.g., by unrolling. Alternatively, the stent itself may be equipped with the bonding agent and then the stent may be connected to the slotted sleeve by unrolling, for example. 
         [0086]    If an agent depot produced according to the present disclosure is used, in particular, for mechanical connection to an endovascular implantable stent, method step c) of the method according to one exemplary embodiment discussed herein additionally comprises the agent depot being cut to the length of a web and/or strut of the stent in sleeve form and the sleeve form being slotted along the axis. The sleeve thus processed represents a clip which is mechanically connectable to the webs and/or struts of the stent using force action and/or adhesive use, preferably in a form-fitting manner. Such a design is shown, in particular, in  FIGS. 2   a,    2   b,    2   c,    4   a,  and  4   c.    
         [0087]    If an agent depot produced according to the present disclosure in film form is used, the agent depot is preferably produced using an extrusion method, casting method, or rolling method. Films may also sometimes be drawn from a melt or solution. 
         [0088]    The method according to the present disclosure for producing the agent depot preferably also comprises, in a method step c), the agent depot in film form being processed in such a manner that the film form is connected to i) the area of the abluminal surface of the body, preferably the stent, or ii) to a part thereof. A film may accordingly be attached around the entire stent and/or a strut of a stent and may, in particular, be attached as in  FIG. 5   a  to the struts at the ends of an implantable stent. If a film is attached to the ends of an implant, preferably a stent, the film is to have a composition which does not project into the lumen and thus impair the unobstructed blood flow. 
         [0089]    If the agent depot produced according to the present disclosure in film form is used for connection to an endovascular implantable stent, the film form i) or ii) of the agent depot used according to the present disclosure is preferably characterized in that the film may be provided perforated corresponding to the geometry of the abluminal surface of the stent, the film material corresponding to the areas of the material of the stent. The films described in  FIGS. 5   a  and  5   b  may accordingly also be provided as perforated, for example, to allow the blood flow into the side branches of blood vessels. 
         [0090]    Agent depots according to the present disclosure in film form may also be connected to the endovascular implantable body, preferably in a form-fitting manner, using suitable means, preferably C-shaped grippers, hooks, and the like. Such an exemplary embodiment is shown, in particular, in  FIGS. 5   a  and  5   b.    
         [0091]    If the agent depot according to the present disclosure is produced as a preform, the agent depot is preferably characterized in that it represents a hollow body which is produced, for example, using a hollow body blowing method or injection-molding method, the preform representing the negative of a point of the implant, preferably a stent, to which it is to be attached. 
         [0092]    If a preform is produced according to a method of the present disclosure for producing the agent depot, the preform may be applied to the body, preferably a stent, by gluing ( FIGS. 7   a - 7   d ), clicking together ( FIGS. 8   a - 8   e ), or by welding together the top and bottom sides and is thus mechanically connectable to the body, preferably a stent, preferably in a form-fitting manner. 
         [0093]    If an agent depot is used as a preform for the connection to an endovascular implantable stent, the preform is preferably processed according to the present disclosure in such a manner that the preform is slotted along the axis or is already provided with a slot when the preform is cast and this preform represents a clip which is mechanically connectable to the stent using force action and/or adhesive use, preferably in a form-fitting manner ( FIG. 4   e ). 
         [0094]    If an agent depot is used as a preform for connection to struts of an endovascular implantable stent, the preform is processed according to the method of the present disclosure in such a manner that the preform is cut to the length of the webs and/or struts of the stent, slotted along the axis or already provided with a slot when the preform is cast, and this preform represents a clip which is mechanically connectable to the webs and/or struts of the stent using force action and/or adhesive, preferably in a form-fitting manner. Such an exemplary embodiment is shown in  FIGS. 1   a,    1   b,    3   b,    4   c,    4   e,  and  5   c.    
         [0095]    The preform may alternatively comprise two parts which are then welded around the strut. 
         [0096]    Agents which are preferably used for an agent depot produced according to the method of the present disclosure are suitable for prophylaxis or therapy of an in-stent restenosis or cancer treatment. Preferably used agents are selected from the group consisting of lipid regulators, immunosuppressives, vasodilators, calcium channel blockers, calcineurin inhibitors, antiphlogistics, anti-inflammatory agents, antiallergy agents, oligonucleotides, estrogens, endothelium producers, steroids, proteins, peptides, proliferation inhibitors, analgesics, antirheumatics, angiogenesis inhibitors, and cytostatics. 
         [0097]    Other agents which may be used include Cytostatics, which particularly include DNA-alkylating substances, in particular nitrogen mustard compounds and nitrosourea compounds; platinum compounds; hydroxyurea compounds; anti-metabolites, preferably folic acid antagonists, purine analogs and pyrimidine analogs; microtubuli inhibitors, preferably Winker alkaloids, taxanes, preferably paclitaxel and dozetaxel; topoisomerase inhibitors; antibiotics, preferably anthracyclines, particularly preferably daunorubicin, doxorubicin, epirubicin, and idarubicin, anactinomycines, in particular dactinomycin, methoxanthrone, asarkrin, and ansarkrin, mitomycin C, and bleomycin; as well as greatly varying cytostatics from the group asparaginase, metefusin, and imatinib; hormones, preferably glucocorticoids, in particular prednisone, sexual hormones, particularly preferably estrogens, gestagens, gonadoliberine (GnRH), fludamid, bizalutamid, tamoxifen, and toremifen, aromatase inhibitors, such as aminoglutetimide, formestan, eksemistan, retrozol, and anastrozol; antibodies, immunomodulators and cytokines, preferably trastuzumab, cetiximab, rituximap, alemtuzumab, daklizumab, gemtuzumab, epratuzumab and ibritumomap; interleukin-II, interferon-α, tumor necrosis factor α (TNF-α), and hematopoietic growth factors, such as G-CSF, GM-CSF. 
         [0098]    If an endovascular implantable body, preferably a stent, more preferably a degradable stent, is mechanically connected to an agent depot produced according to the method of the present disclosure, preferably in a form-fitting manner, the method preferably additionally comprises one of the bodies from step a) of the method being entirely or partially coated with one or more auxiliary agents before connection to the agent depot in step c), the auxiliary agents reinforce the mechanical connection of the agent depots to the body or bodies. 
         [0099]    According to the present disclosure, adhesives are preferably used as the auxiliary agent, preferably pure plastic solvents, instant adhesives from the group consisting of acrylates, fibrin adhesives, fats, and polysaccharides. 
         [0100]    According to a preferred exemplary embodiment of the method for the production of the endovascular implantable body charged with agent, preferably a (degradable) stent, if a sleeve form is used as the agent depot, the sleeve preferably corresponds to the length of a web or strut of the stent, is slotted along the axis, and thus represents a clip which is mechanically connected in method step c) using force action and/or adhesive use to the web or strut of the stent, preferably in a form-fitting manner. 
         [0101]    If an agent depot produced according to the present disclosure in film form is used, preferably film i) or ii) being used, the endovascular implantable body, preferably a degradable stent, is unrolled having the abluminal surface on the film i) or ii) in step c) and is thus mechanically connected using force action and/or adhesive use, preferably in a form-fitting manner. 
         [0102]    If a preform is used, the production method according to the present disclosure, the preform is glued, clicked (snap-fitted) together, or welded together in step c) onto the implantable body, and is thus mechanically connected to the body, preferably in a form-fitting manner. 
         [0103]    Alternatively, the preform may also be attached to the implantable body by shrinkage with decentralized heat supply, so that the agents are not damaged. 
         [0104]    Alternatively, an exemplary method according to the present disclosure for producing the agent-charged endovascular implantable body is characterized in that, in a further step, the preform is processed so that the preform is slotted along the axis or is already provided with a slot when cast and this preform represents a clip which is mechanically connected in step c) to the body, preferably a stent, using force action and/or adhesive use, preferably in a form-fitting manner. 
         [0105]    The preform is preferably cut to the length of a web or a strut of the stent, slotted along the axis or already cast having a slot, so that the preform represents a clip which is mechanically connected in step c) to the web or strut of the stent using force action and/or adhesive use, preferably in a form-fitting manner. 
         [0106]    Insofar as the agent-charged endovascular implantable body represents a stent producible according to a method of the present disclosure, the agent-charged endovascular implantable body is preferably a degradable endovascular implantable stent, especially preferably a degradable metal stent. The preferred designs described herein for the production method according to the present disclosure are to be applied to the present implantable body according to the present disclosure, preferably a degradable stent. 
         [0107]    Insofar as the present disclosure relates to a kit, the preferred embodiments which relate to the agent depot or the endovascular implantable body are explained in greater detail by the preferred exemplary embodiments described of the production method according to the present disclosure. 
         [0108]    Exemplary embodiments for the use according to the present disclosure of one or more agent depots for producing an agent-charged implantable body or for the method according to the present disclosure for prophylaxis or treatment of a stenosis, an aneurysm, or a tumor tissue may be achieved in that one or more of the above-mentioned preferred exemplary embodiments are received in the body. The agent or agents are attached especially for the particular therapy. The term agent is to be understood as comprising one or more agents. 
         [0109]    A high concentration of agent(s) is preferably used for the prophylaxis or therapy of a tumor tissue. Accordingly, those agent depot forms which may contain a high concentration of agent are preferred for an exemplary embodiment according to the present disclosure. For example, suitable agent depots are shown in  FIGS. 3   a,    3   b,    5   a,    5   b,  and  5   c.  An agent-charged stent producible according to the present disclosure is preferably implanted in a blood vessel which carries blood to the tumor, preferably in proximity to the tumor tissue. 
       DETAILED DESCRIPTION 
       [0110]      FIG. 1   a  shows an abluminal detail of a stent geometry  2  (the stent geometry is described in U.S. Pat. No. 6,896,695), together with multiple, preferably form-fitting, clipped-on agent depots  1  in the form of slotted beads  11  the agent depot beads  11  according to the present disclosure have a cavity and are slotted  111  in such a manner that the beads may be clipped, in particular, onto the longitudinal connectors (struts)  21  or alternatively onto the linear areas of the stent struts  22  (latter embodiment not shown), preferably in a form-fitting manner (see also  FIG. 1   b ). Such a design according to the present disclosure is preferable for one or more agents which have a good distribution into the vascular tissue after release of the agent(s). 
         [0111]    Due to the high proportion of a non-agent-charged stent main body  2 , improved overgrowth with endothelial cells (“EC”; endothelialization) may be made possible in relation to typically completely coated stents from the prior art. Due to this improved endothelialization of the stent  2 , the risk of a thrombosis which is connected to the implantation of an endovascular implantable body may also be reduced. 
         [0112]      FIG. 1   b  shows a view of agent depot beads  11  according to one exemplary embodiment of the present disclosure having a slot  111  and a cavity  112 , which is designed so that the agent depot beads may be clipped onto a strut  21  or web  22  of a stent  2 , preferably in a form-fitting manner. These agent depot beads  11  may comprise one or more agents according to the present disclosure. The agent depot beads  11  used may also each comprise different concentrations of one or more agents. 
         [0113]    Agent depots according to the present disclosure in the form of beads  11  are preferably produced using casting, film, and joining methods. 
         [0114]      FIG. 2   a  shows an abluminal detail of a stent geometry  2  (which is described in U.S. Pat. No. 6,896,695) having multiple clipped-on agent depots  1  in sleeve form  12 . The sleeves  12  are slotted  126  along the longitudinal side and have a cavity  127  to be able to be clipped, in particular, onto the longitudinal connectors (struts)  21  or alternatively onto the linear areas of the stent struts  22  of a stent  2 , preferably in a form-fitting manner (see also  FIG. 2   c ). Such an agent charge according to the present disclosure is preferably of interest for a surface-covering charge having two, three, or more agent depots ( 121 ,  122 , and  123 ). A multiple drug release, in particular, a dual-drug release (release of two agents) or a triple-drug release (release of three agents) may thus be made possible. 
         [0115]    Such a design is also preferable, in particular, for those agent depots whose polymer may not be connected according to typical coating methods to the main body of the stent or the implantable body because of a lack of suitable solvents or polymer adhesion to the stent material used. 
         [0116]      FIG. 2   b  shows a design as an alternative to  FIG. 2   a.  In this design according to the present disclosure, the areas  23  of the stent have a lower charge of the agent depots  12 , i.e., fewer agent depots  12  per unit area of the stent  2 , in relation to the areas  24  of the stent. The agent depots  12  are preferably clipped in a form-fitting manner onto the web  22  or strut  21  of a stent  2 . 
         [0117]      FIG. 2   c  shows a view of the slotted agent depots according to one aspect of the present disclosure in sleeve form  12 , a slot  124  and a cavity  125 , which is designed in such a manner that it may be clipped onto a strut  21  or web  22  of a stent  2 , preferably in a form-fitting manner. An agent depot  12  may typically contain one or more agents. Agent depots  121 ,  122 , and  123  differ in that the agent depots each comprise a different agent. 
         [0118]    Agent depots according to the present disclosure in sleeve form  12 ,  121 ,  122 , and  123  are preferably produced using extrusion methods, blow-molding methods, and deep-drawing methods. In rare cases, joining or gluing technology is used. 
         [0119]      FIG. 3   a  shows a view of an abluminal detail of a stent geometry  2  having multiple flat slotted agent depots  13  in preform, which are clipped onto struts  21  or webs  22  of a stent  2 , preferably in a form-fitting manner. 
         [0120]      FIG. 3   b,  in particular, shows that the agent depot  13  according to the present disclosure is designed in such a manner that the agent depot comprises a C-shaped gripper  131  having slot  133 , which may be clipped onto a strut  21  or web  22  of a stent  2 , preferably in a form-fitting manner, and a matrix  132 . Agent depots  13  according to the present disclosure comprise one or more agents and are preferably produced using casting methods, possibly combined with milling or plugging together or using a suitable joining method (hot gluing, gluing, for example) or injection-molding method. 
         [0121]    A high agent concentration of the agent depot  13  is made possible using agent depot  13  shown in  FIGS. 3   a  or  3   b.  The agent concentration is preferably localized in the matrix material  132  of the agent depot  13  which is situated on the abluminal surface of the implantable body, preferably a stent. In this way it is possible that little to no agent is discharged from the agent depot  13  into the vascular lumen from an implanted stent  2  and thus an endothelialization of the stent  2  is not delayed or prevented. The risk of a restenosis or a thrombosis is accordingly reduced according to the invention of the present disclosure. 
         [0122]      FIG. 4   a  shows a top view of an abluminal detail of a stent geometry  2  having multiple agent depots  14  and  15  which are clipped onto the abluminal surface on struts. This design is comparable to the design according to the invention disclosed in  FIG. 3   a,  with the difference that the agent depots  14  and  15 , in contrast to the agent depot  13 , are not clipped onto the struts  21  and webs  22  of the stent  2 , rather, the agent depots are freely rotatable around the struts and webs of the stent. It is made possible by an exemplary embodiment shown in  FIG. 4   a  that by using the agent depots  14  and  15  on the luminal surface of the charged stent  2 , little polymer and/or agent of the particular agent depot  14  or  15  is present and thus an endothelialization of the implanted stent  2  is not decreased or prevented. The risk of a restenosis or thrombosis decreases accordingly. 
         [0123]      FIG. 4   b  shows a perspective view of an agent depot  14  according to the present disclosure. The agent depot  14  comprises means  141  which are mechanically connectable to a strut  21  or a web  22  of a stent  2 , preferably in a form-fitting manner. According to  FIG. 4   b,  the means  141  particularly represent a hook shape. These means may be produced from the same material as the agent depot. An agent depot  14  according to the present disclosure is also preferably designed such that the agent depot at least partially covers the abluminal surface of a strut  21  and/or web  22  of the stent  2  in the clipped-on state. Little to no polymer, and preferably little agent-containing polymer of the agent depot  14  or  15 , is preferably present on the luminal surface of the stent  2 . 
         [0124]      FIG. 4   c  shows a perspective view of an agent depot  15  according to one aspect of the present disclosure. Agent depot  15  is designed as a sleeve and/or preform. The agent depot has a slot  151  and a cavity  152  which may be clipped onto a strut  21  or web  22 , preferably in a form-fitting manner. Furthermore, the agent depot  15  comprises material which covers the abluminal surface of a strut  21  or web  22  in the clipped-on state. In a preferred design, the slot  151  is wide enough that the agent depot  15  has little or no matrix material of the agent depot  15  on the luminal side in the state clipped onto the strut  21  or web  22  of the stent  2 . 
         [0125]      FIG. 4   d  shows a top view of an abluminal detail of a stent geometry  2  having multiple agent depots  16 . The agent depots are designed such that, in the clipped-on state, the agent depots cover both the luminal and also the corresponding abluminal areas of one or more webs  22  and/or struts  21  of a stent  2 , preferably in a form-fitting manner. 
         [0126]      FIG. 4   e  shows a perspective view of an agent depot  16 , which is designed so that, in the clipped-on state, the agent depot covers both luminal and also the corresponding abluminal areas of one or more webs  22  and/or struts  21  of a stent  2 , preferably in a form-fitting manner. For this purpose, the agent depot  16  has an upper area  161  which preferably covers the abluminal surface of a stent  2 , and a lower area  162 , which preferably covers the luminal surface of a stent  2 . In addition, an agent depot  16  according to the present disclosure has a slot  163  which allows the agent depot  16  to be clipped onto one or more webs  22  and struts  21 . Preferably, an agent depot according to this aspect of the present disclosure comprises cavities  164  which enclose the webs  22  and struts  21  of a stent  2  in the clipped-on state, preferably in a form-fitting manner. One or more agents are preferably incorporated solely in the area  161  of the agent depot. This has the advantage that, due to a decreased discharge of the agents to the vascular lumen, the endothelialization of the stent  2  is not decreased or prevented. 
         [0127]      FIG. 5   a  shows a top view of an abluminal detail of a stent geometry  2  having terminal, preferably form-fitting, clipped-on agent depots in the form of a strip  17  or a body  18 . Such an exemplary embodiment according to the present disclosure is more rarely used for an antiproliferative use of a drug-eluting stent (DES), but rather preferably for the release of agents, in particular, selected from the group of cytostatics into the bloodstream for treating tumors. In this exemplary embodiment according to the present disclosure, the stent is not used because of its support structure, but rather is used as an anchor for the agent depots  17  and  18 . A stent charged in this manner is preferably implanted in a blood vessel which carries blood to the tumor tissue, preferably in proximity to the tumor tissue. In this way, it is possible for the highest possible concentration of agent used to reach the tumor tissue. 
         [0128]      FIG. 5   b  shows a perspective view of an agent depot according to the present disclosure in strip form  17 . The strip  17  also has means  171  which allow the strip  17  to be mechanically connected to an endovascular implantable body, preferably a stent. Preferably, means  171  in the form of a C-shaped gripper having a slot  171  are used. In the clipped-on state the C-shaped gripper  171  encloses a web  22  or a strut  21  of a stent  2 , preferably in a form-fitting manner. This agent depot  17  may comprise one or more agents. 
         [0129]      FIG. 5   c  shows a cross-section of an agent depot in the form of a body  18 . The body  18  also has means  181  which allow the body  18  to be able to be mechanically connected to an endovascular implantable body, preferably a stent. Preferably, means  181  in the form of a C-shaped gripper which has a slot  181  are used. In the clipped-on state, the C-shaped gripper  181  encloses a web  22  or a strut  21  of a stent  2 , preferably in a form-fitting manner. This agent depot  18  may comprise one or more agents. The C-shaped gripper may be produced, for example, using injection molding, reservoir, by joining methods (gluing, fusion, for example) or according to suitable other methods described hereinabove. 
         [0130]      FIG. 6   a  shows a top view of an abluminal detail of a stent geometry  2  having terminally attached agent depots  19  in cap form, which are shrunk onto the webs  22  of a stent  2 , preferably in a form-fitting manner. The agent depots  19  are preferably shrunk onto the round terminal areas of the stent  2  with decentralized heat supply so as not to damage the agents. 
         [0131]      FIG. 6   b  shows a perspective view of an agent depot  19  having the surface  191  toward the vascular lumen or toward the vascular tissue and the internal surface  192  toward the webs  22 . 
         [0132]      FIG. 7   a  shows a schematic abluminal view of a detail of the stent geometry  2  having stent struts  22  and an agent depot  1  in film form which is glued onto the stent struts  22 , preferably using instant adhesives from the group consisting of acrylates, fibrin adhesives, fats, or polysaccharides. Alternatively, the agent depot  1  may have concave points and thus be glued in a form-fitting manner onto the stent struts  22 . 
         [0133]      FIG. 7   b  shows a cross-section of a stent strut  22  having an agent depot  1  in film form. 
         [0134]      FIG. 7   c  shows a cross-section of a stent struts  22  having agent depot  1 , the agent depot is situated on the abluminal surface of the stent strut  22  and correspondingly only a small component of the agents which is contained in the agent depot  1  being discharged to the vascular lumen. This is advantageous because the endothelialization of the stent is thus encouraged and the side effects of the stent as a foreign body are reduced. 
         [0135]      FIG. 7   d  also shows a cross-section of a stent strut  22  having agent depot  1  which is also situated on the abluminal side of the stent strut. Only small quantities of agent are discharged from the agent depot  1  to the vascular lumen. The advantages as described for  FIG. 7   c  also exist here. 
         [0136]      FIG. 8   a  shows a cross-section of a stent strut  22  having an agent depot  1  enclosing the stent strut and connection mechanism  30 . 
         [0137]      FIG. 8   b  shows the connection mechanism  31  of the agent depot  1  in an enlarged form. The connection mechanism  31  is a notch which may be introduced by milling into the agent depot at one end of the agent depot and a protrusion which is suitable for being plugged fitting into the notch at the diametrically opposite second end of the agent depot to thus cause a solid connection of the two ends of the agent depot. 
         [0138]      FIG. 8   c  shows the connection mechanism  32  of the agent depot  1  in enlarged form. The connection mechanism  32  is a connection mechanism having an L-shape, the diametrically opposite ends of the agent depot each having mirror-reversed L-shaped ends which may be plugged fitting into one another and thus cause a solid connection of the ends of the agent depot  1 . 
         [0139]      FIG. 8   d  shows a connection mechanism  33  of the agent depot  1  in enlarged form. The connection mechanism  33  is characterized in that the two diametrically opposite ends of the agent depot  1  are each provided in hook form and may be hooked in one another and thus cause a solid connection of the ends of the agent depot  1 . 
         [0140]      FIG. 8   e  shows a connection mechanism  34  of the agent depot  1  in enlarged form. The connection mechanism  34  fundamentally corresponds to the connection mechanism in L-shape, as is already described in  FIG. 8   c,  but the connection mechanism  34  differs in that the face  341  has protrusions and the face  342  has corresponding notches which press against one another and thus cause a solid connection of the ends of the agent depot  1 . 
         [0141]      FIG. 9   a  shows a cross-section of a stent strut  22  having agent depot  1  which is situated overlapping in the area  4 . This type of the connection may be attached in the position  4  either by the intrinsic tension of the agent depot  1  or by a suitable adhesive. Exemplary adhesives such as acrylates, fibrin adhesives, fats, and polysaccharides are suitable as preferred adhesives. 
         [0142]      FIG. 9   b  shows a cross-section of a stent strut  22  having agent depot  1 , which overlaps in the area  4  and a further agent reservoir  5  which is preferably situated on the abluminal side. In this exemplary embodiment, the agent depot  1  preferably has no agent. The agent depot is put into its shape either by intrinsic tension or by additional gluing in the area  4 . In this design, the reservoir  5  of the agent depot  1  has one or more agents, preferably antiproliferative agents. 
         [0143]      FIG. 9   c  schematically shows a cross-section of the agent reservoir  5  of the agent depot  1 , as shown in  FIG. 9   b,  now as an agent reservoir  51  having a homogeneous agent distribution of one or more agents. 
         [0144]      FIG. 9   d  shows the agent reservoir  5  of the agent depot  1  from  FIG. 9   b  as the reservoir  52 , the agent being distributed homogeneously and a top coat  53  being coated over this layer, which influences the release of the agents in the reservoir  52 . 
         [0145]      FIG. 9   e  shows an agent reservoir  5  of an agent depot  1  from  FIG. 9   b  in a preferred design. The reservoir  52  contains a homogeneous distribution of an agent and the reservoir  54  contains a homogeneous distribution of a further agent. A dual-drug application is thus made possible. 
         [0146]    All patents, patent applications and publications referred to herein are incorporated by reference in their entirety.