Implant and method for manufacturing same

p0001The present invention relates to an implant, in particular an intraluminal endoprosthesis, with a preferably hollow-cylindrical basic structure, a system comprising a catheter and such an implant and a process for producing such an implant or of such a system.

p0002Medical endoprostheses or implants for various applications are known in a large variety of the prior art. As implants in the context of the present invention, endovascular prostheses or other endoprostheses, such as stents (vascular stent, biliary stent, Vascular stent (including the heart and the heart valve stent), mitral stent), endoprostheses are for closing persitierenden foramen ovale (PFO) , Pulmonalklappenstent (pulmonary valve stent), Implants for closing an ASD (atrial septal defect, atrial septal defect) and prostheses in the area of ​​hard and soft tissue to understand.

p0003Nowadays, particularly frequently as implants stents, which are used for treatment of stenoses (vascular constrictions). They have a perforated tubular or hollow cylindrical basic structure which is open at both longitudinal ends. The basic structure thus has a plurality of through openings. The basic structure of the stent often composed here of individual meshes together which of variously shaped webs (Struts), for example, zigzag or meander-like webs, are formed. Such an endoprosthesis is often used via a catheter into the vessel to be treated and serves to support the vessel over a longer period (months to years). The use of stents, constricted areas in the vessels can be expanded so that a lumen gain results. namely through the use of stents or other implants, an be achieved for successful treatment primarily necessary optimum vessel cross-section, but the permanent presence of a stent, which is a foreign body in itself, a cascade of microbiological processes, for example, inflammation (inflammation) of the favoring treated vessel or a vessel necrotic changes and / or which may lead to a gradual blockage of the stent by forming plaques or coagulation of body fluid as a result of flow variation or due to an infectious process.

p0004To prevent restenosis or inflammations and necrosis, stents or other implants are frequently provided with a coating of drugs that have, for example, an anti-coagulant or anti-inflammatory effect. Here, it is desirable that the implants release the pharmaceutically active substances more effectively.

p0005There are already stent with drug delivery from a coating known which may for example consist of a polymer. In addition, already drug depot can be used with pumps. A disadvantage of the known solutions is, however, that the pharmaceutically active substances are released continuously and no control of the release is possible. Moreover, only a constant dose of the substances can be realized and the remainder of the drug can not be detected in the reservoir or depot. The organism of the treated human or animal is unnecessarily burdened by the sustained release of the ingredients.

p0006The publication <patcit id="pcit0001" dnum="US7060093B2"><text>US 7,060,093 B2</text></patcit> discloses a stent, which recesses (depots) in the webs. These deposits contain drugs and give them later on. The drug release from such deposits is also difficult to control and has a relative unfavorable to the inner surface of the treated vessel distribution of drugs on this surface. This also leads to a greater load on the organism being treated, as to ensure an adequate supply of medicines in all the necessary areas of the organ being treated, locally overdosing is effected, which may cause toxic reactions.

p0007The object of the present invention is therefore to provide an implant which enables a more focused and the body less burdensome delivery of a drug. In addition to a cost-effective system of an implant and a catheter provided as well as a simple method for the manufacture of such an implant or of such a system are given.

p0008The above object is achieved by an implant, wherein at least 20% of the cross-sectional area, preferably at least 50% of the cross-sectional area, at least a portion of the openings of a predetermined portion of the base structure, preferably the openings of the predetermined section with the smallest cross-sectional area, more preferably at most 95 % of the total cross-sectional areas of all openings of the predetermined portion is covered or straddles in dilated state with at least one pharmaceutically active substance-releasing coating. For this purpose, the coating comprises at least one pharmaceutically active substance, for example in pores. Here, in the non-dilated state, for example, in the crimped state, in which the implant is crimped onto a balloon, the coating having apertures be completely covered. Only during the Dilatierens can tear the coating, for example along a predetermined breaking point, so that in the expanded state, a smaller portion of the cross-sectional area of ​​the respective openings is covered. This can be done in advance to calculate the behavior of the coating in a simulation on a FEM analysis (finite element analysis). This is possible to tailor the properties of the coating.

p0009In relation to the present invention is called 'cross-sectional area' is the area meant, which spans the respective opening along the abluminal plane of the casing of the implant. In other words, corresponds to the cross-sectional area of ​​the area of ​​the opening which is visible when a viewer is looking from the outside onto the opening. The coating extends from the basic structure surrounding the respective opening into the aperture and spanning this similar to a 'skin'. the layer thickness of the coating is preferably at most 100 microns.

p0010The inventive implant has the advantage that there is now a large area for the delivery of drugs available. This area is, for example, significantly greater than the area of ​​the webs, which serve in the art for delivery of the drug. A more even distribution of the pharmaceutically active substance across the area to be treated, for example the inner wall of a vessel, is thus achieved. Consequently, an overdose of the pharmaceutically active substance in the area of ​​the organ being treated can be avoided, so that side effects such as toxic reactions no longer occur.

p0011Due to the large, available for delivery of pharmaceutically active substance surface luminal delivery of pharmaceutically active substance is also not necessary, the abluminal supply of the pharmaceutically active substance is sufficient. Consequently, the invention provides that the pharmaceutically active substance is released at least predominantly in abluminal direction from the coating. Preferably at least 95 wt% is. The leave at least one pharmaceutically active substance from the coating in abluminal direction. This is advantageous because the luminal delivery of drugs can hinder ingrowth of the implant or endothelialization. Therefore, due to the lack of luminal delivery of the drug sufficient Endothealialisierung the implant with the inventive solution is added and it can be a late thrombosis are avoided. The delivery of the at least one pharmaceutically active substance is carried out by the distention of pores having the coating, during and after the dilatation of the implant. The release of which is arranged in the matrix of the coating at least one pharmaceutically active substance is thus not initialize or excited by the dilatation of the implant. Further, the open pores of the coating provide an engagement surface for the degradation of the polymer matrix, preferably consisting of a use, when degradable materials for the coating matrix are employed.

p0012The pores for the inclusion of the pharmaceutically active substance may be provided as a coating material, for example by use of a porous polymer. Alternatively or additionally, pores in a mechanical way, for example, can be produced by punching. Here, the material of the coating is first severely stretched, then the pores are punched and then the material is relieved again. The filling is then also under stretching of the coating material. After hardening of the filling, that is the pharmaceutically active substance, the coating material is entlastest, so that the polymer returns to its original shape. In the above described expansion of the coating material of the strain range of plastic deformation is to be avoided. This method is applicable both for "normal" polymers as well as shape memory polymers. Another way to introduce pores in the coating, is the etching.

p0013Further, it is possible to prepare the implant for a predominantly abluminal delivery of the pharmaceutically active substance. According to an embodiment of the present invention, the coating has a plurality of layers (layers), the first, most arranged in luminal direction layer is preferably formed as a diffusion barrier for the at least one pharmaceutically active substance. Accordingly, in this embodiment, a multi-layer coating is used, with first a layer (layer) is applied, which does not contain any pharmaceutically active substance. This is preferably made of a polymer or a degradable material layer serves as a diffusion barrier or diffusion barrier for the pharmaceutically active substance and is arranged in the coating furthest in luminal direction. After this layer has hardened, at least one further layer is applied over it, which is embedded in its matrix comprises at least one pharmaceutically active substance. The material of the matrix may also be made biodegradable.

p0014In a further embodiment, may be provided in the coating one or more predetermined breaking points (as a predetermined breaking line in the form of along a line attached Lochperforationen in the coating or a linear reduction of the layer thickness of the coating, for example), which tear defined during dilatation of the implant. This facilitates in particular the release of the contained in the coating pharmaceutically active substance.

p0015According to the invention, if necessary, to provide only predetermined portions of the base structure, for example, only the ends of the implant in the direction of a longitudinal axis of the implant with the coating with the pharmaceutically active substance, the effects as Dogboning, flow-induced proliferation at the ends of the implant or the like prevent. That in the predetermined portion of the base structure only locally administered drug can selectively act where it is needed and does not have to be placed unnecessarily along the entire axis of the implant.

p0016Due to the total required lower concentration of the pharmaceutically active substance is also the degradation of the implant, if the basic structure consists of a degradable material, not unnecessarily influenced by the substance pharmaceutically active. The substance can be eluted as undisturbed and effective against restenosis.

p0017In the context of the present invention is meant a plant, animal or synthetic active ingredient (drug) or a hormone with a pharmaceutically active substance (or therapeutically active or effective substance), which in a suitable dosage as a therapeutic agent for influencing states or functions of the body, as finds replacement for naturally produced by the human or animal body substances such as insulin, as well as to eliminate or to render harmless pathogens, tumors, cancer cells or exogenous substances use. has the release of the substance in the endoprosthesis has a positive effect on the healing process or acts pathological changes in the tissue resulting from surgical procedures or counter is used to render malignant cells harmless in oncology.

p0018Such active pharmaceutical substances have an anti-inflammatory and / or antiproliferative and / or spasmolytic effect, whereby, for example, restenosis, inflammation, or (vascular) spasms can be avoided. Such substances may, in particularly preferred embodiments of one or more substances from the active substance group of calcium channel blockers, lipid regulators (such as fibrates), immunosuppressants, calcineurin inhibitors (such as tacrolimus), antiphlogistics (such as cortisone or diclofenac), anti-inflammatory agents (such as for example imidazole), the antiallergic agents of oligonucleotides (such as dODN), estrogens (such as genistein), endothelium (such as fibrin), steroids, analgesics, the anti-inflammatory drugs of proteins, hormones, insulins, cytostatics , peptides, vasodilators (such as sartanes) and antiproliferative (proliferation-inhibiting) acting substances taxole or taxanes, here preferably paclitaxel or sirolimus, or to the following list are taken: cisplatin, tirapazamine, enzymes L-asparaginase, methotrexate , 5-fluorouracil, azathioprine, mitoxantrone, cyclophosphamide, methotrexate, natalizumab, adriamycin PFS, adriamycin RDF, alitretinoin, Altretamine, Aromasin, Azathioprine, Bicalutamide, busulfan, Busulfex, Capecitabine, Casodex, Cyclophosphamide, Cytoxan, doxorubicin, Exemestane, Femara, Finasteride , gemtuzumab, ozogamicin, Hexalen, Imuran, Letrozole, Mifeprex, Mifepristone, Myleran, Mylotarg, Neosar, Nolvadex, Panretin, Propecia, Proscar Rubex, tamoxifen, Temodar, Temozolomide, Trelstar Depot, triptorelin, Genasense (Fa.Genta) INGN201 ( Fa.Introgen Therapeutics), SCH58500 (Fa.Schering-Plough), ONYX-015 (Fa.Onyx Pharmaceuticals), E1A-lipid complex (Fa.Targeted Genetics), TRAIL (Fa.Genentech / Immunex), GX01 (Fa.Gemin X Biotechnologies), cyclosporin A, DPPE, PSC 833, Buthionine sulphoximine, dexverapamil, Quinine, verapamil, XR9576, Dexniguldipin, GF120918, Lobradimil, LY335979, MS209, R-101933, Gemtuzumabozogamicin, SGN-15, MCC-465, SB-408075 , A5B7 antibody against CEA with carboxy peptidase A + mustard prodrug, Amifostine, Dexrazoxane, BB-10010, transfer of MDR genes, BNP7787, tirapazamine, Aplidine, Arsenic trioxide, BMS-247550, CHS828, CT 2584, dolastatin-10, ET- 743, exisulind, Irofulven, KW-2189, lovastatin, E7070, LU103793, LY355703, Pyrazoloacridine, TLK286, Apomine, CP-461, EP0906, FB642, FK317, FK866, Kahalalide F, LAF389, PNU-166196, RO 31-7453, cetuximab (Erbitux), trastuzumab (Herceptin), ABX-EGF, AP12009, EMD55900, EMD72000, ICR62, 2A11, CCI-779, ISIS 3521, oblimersen (Genasense), OSI-774 (Tarceva), PS-341, R115777 ( Zarnestra), STI571 (Gleevec), ZD1839 (Iressa), bryostatin-1, flavopiridol, GD0039, GEM231, Ilmofosine, ISIS 2503, ISIS 5132, L-778 123, PKC 412, SCH 66336, SU-101, UCN-01 , Bay 43-9006, BMS-214662, CI-1040, GW572016, LErafAON, LY-317615, perifosine, Phenoxodiol, PKI 166, Swainsonine, 17-AAG, decitabine, CI-994, depsipeptides, MG98, phenylbutyrate, phenylacetate, Suberoylanilidehydroxamic acid, Adp53, Antineoplastons, A10 / AS2-1, OL (1) p53, p53, RPR / INGN-201, SCH 58500, HSV-TK VPC, tgDCC-E1A, INX3280, TK gene pioglitazone, troglitazone, BAY12-9566, BMS-275 291, clodronate, marimastat, Prinomastat, MMI270, COL-3, CP-471.358, trans retinoic acid, bexarotene, Pivaloyloxymethylbutyrate, 9-cis-retinoic acid, 13-cis RA, Fenretinide, ILX23-7553, TAC-101, tazarotene, bevacizumab, rhuMAb-VEGF, HuMV833, Angiozyme, IMC-1C11, PI-88, SU5416, CP547,632, PNU-145156E, PTK / ZK 787, SU6668, ZD6474, Carboxyamidotriazole, GBC-590, Squalamine, Vitxain, ABT -510, CM101, ZD6126, Neovastat, suramin, Thalidomide, IM862, TNP-470, angiostatin, CC-5013, combretastatin A-4, endostatin, interleukin-12, alemtuzumab, edrecolomab, Epratuzumab HuM195, Oregovomab, rituximab, ch14.18, MDX -11, WX-G250, 3F8, H22xKI-4, ING-1, J591, KM871, Immunoconjugates antibody with toxin, BL22, anti-Tac-PE38 (LMB-2), BB-10901, SS1-PE38, denileukin diftitox ( Ontak), IL13-PE38QQR, TP-38, Allovectin-7, 105AD7, Bec2, TriGem, 1A7, 3H1, Vaccines, MDX-H210, G17DT, MDX-447, EMD 273063, IL-2 / histamine, LAK, TIL, CTL, Bay 50-4798, MDX-010, OK-432, PSK, Ubenimex, GM-CSF, ONYX-015, NV1020, PV701, Reolysin, celecoxib, Lyprinol, LY293111, Astra Sentan, melatonin, Taurolidine, cyclosporin A, verapamil, tirapazamine trastuzumab, clodronate, trans retinoic acid, edrecolomab, rituximab, OK-432, Ubenimex, melatonin, PSC 833, R115777, ZD1839, SCH 66336, decitabine, HSV-TK, VPC, BAY12-9566, marimastat, Prino mastat, suramin, 105AD7, IL-2 / histamine, Astra Sentan.

p0019In order to achieve a sufficiently large expansion of the coating, it is often sufficient, if a maximum of every second of the adjacent through-holes of the predetermined portion of the basic structure with the at least one pharmaceutically active substance-releasing coating covers or spans.

p0020A particularly simple construction of the implant, in particular stent, is achieved in that the basic structure of closed cells or meshes is assembled, each cell having an aperture therethrough. Preferably, each cell is formed by two or more, if appropriate, bent and / or curved webs.

p0021It is advantageous if the material of the coating comprising the pharmaceutically active substance is formed elastically. Preferably, the material of the coating has a modulus of elasticity in the range of 0.01 kN / mm² to 4 kN / mm², Preferably in the range of 0.01 kN / mm² to 2 kN / mm², on. The corresponding extensibility or the corresponding elasticity of the material of the coating is 100% to 800%, preferably 300% to 800%. This makes it possible to perform a dilation of the implant, without the coating being damaged.

p0022It is also advantageous if as a result of, for example dilatationsbedingten elongation of the material of the coating, the elution (release) of the pharmaceutically active substance in certain areas of the coating, for example in the middle of a coating of an opening, faster start than in other areas. This ensures that the pharmaceutically active substance is released over a longer period and is not immediately flushed to the start of treatment. This kinetics can be controlled by the given by the mechanics of the basic structure of dilation and the design of the coating.

p0023It is further preferred if the coating contains at least one polymer of the group comprising the polymers of the class of elastomers, particularly rubber, and latex, further comprising PET (polyethylene terephthalate), PS (polystyrene), PA (polyamide), PUR (polyurethane), PE ( polyethylene), PES (polyethersulfone), polytetrafluoroethylene (PTFE, Teflon®), PLA (polylactide, polylactic acid), PLLA (poly-L-lactide), PLGA (poly-L-glycolide), PGA (polyglycolide), PBMA (poly- butyl Methacrylate), PEVA (polyethylene vinyl acetate), shape memory polymers, and blends thereof, and copolymers and block polymers. Examples of polymers with shape memory effect are multi-block copolymers or standard polymers (PET, PS, PU, ​​PE, PES, PTFE). Said polymers are particularly well suited to accommodate a pharmaceutically active substance in various forms and those at the treatment site and releasing it again, since these polymers are highly elastic and not tear at small strains. Further, many of the polymers mentioned have the properties listed above in relation to their elasticity, since the implant is often dilated at the treatment site. Preferably, the material of the coating is biocompatible and possibly also degradable.

p0024Shape memory polymers (FGP) are plastics, which have a shape memory effect, so can "remember" their earlier external shape despite a temporary strong deformation apparently. Such shape memory polymers are typically made up of two components. The first is an elastic polymer, a kind of "spring element". The second component is a curable wax which the "spring member" can lock after curing in any desired form. Now, if the shape memory polymer is heated, the wax becomes soft and therefore the force of the elastic polymer no longer counteract (1 component). The shape memory polymer increases in this state, returns to its (original) form. The aforementioned shape memory polymers (FGP) are particularly well suited to accommodate a pharmaceutically active substance in various forms and those at the treatment site and releasing it again, because in these polymers pores can be "programmed" that only during and after the dilation on implantation are opened and thus can enable at least one pharmaceutically active substance. The provision or preparation ( "hardcoding") of pores in the coating material containing at least one shape memory polymer has been shown above.

p0025In a further embodiment, the coating, which is designed in layers or skin-shaped, connected by means of an adhesive connection, a form-fit and / or material connection (ie, by means of a chemical compound) having the basic structure, for example, the coating with the pharmaceutically active substance to the the basic structure forming webs attached. For this purpose, the basic structure of the implant, preferably a part of the webs, in one embodiment, preferably on the abluminal side of the groove for fixing the coating on

p0026The basic structure of such an implant may preferably be at least one element and / or a compound from the following group consisting of metals, metal alloys, preferably stainless steel, CoCr, magnesium alloys, iron alloys, zinc alloys, manganese alloys, nitinol, polymers from the class of biodegradable polymers, preferably polylactic acid, poly-caprolactone, mixtures or copolymers thereof, polymers from the class of biocompatible polymers, preferably UHMWPE and PEEK containing. Here, an implant is designed as a stent consisting of a biodegradable magnesium alloy, iron alloy, zinc alloy or manganese alloy as AMS (= absorbable metal stent) respectively.

p0027Determining the position of a stent is often done by means of imaging processes, for example by means of an X-ray device. Since the materials used for the fundamental lattice of stents typically X-ray radiation absorbing only a small extent, that is, X-ray or are radiolucent, the implant is provided in an embodiment of the invention with at least one X-ray marker which contains a material of a higher absorption X-ray comprising (also referred to as radiopaque or radiopaque material) than the surrounding material it. The radiopaque material is contained in the coating preferably in liquid form, for example as pure iodine. Here, the liquid X-ray opaque material is processed during the coating process together with the material of the matrix. It hardens later, or it is determined in a different way and is after the completion of the coating process, ie prior to the crimped stent and the introduced into the body and possibly dilated stent, in solid form. Alternatively may be in encapsulated form the radiopaque material. Here, the material of the microcapsule is biocompatible and non resorbable. The radiopaque material can, for example, as gold, silver or tantalum particles comprise. The microcapsules preferably have a size of 0.5 micron to 1 micron.

p0028Such x-ray marker comprises radiopaque material, namely one or more of the elements and / or compounds from the group comprising gold, platinum, silver, tungsten, iodine, tantalum, yttrium, niobium, molybdenum, ruthenium, rhodium, barium, lanthanum, cerium, praseodymium, neodymium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium, hafnium, rhenium, osmium, and bismuth, and a radio-opaque compound of these elements, in particular the complexes, if they are present in salt form, and barium sulfate, bismuth trioxide, bromine, iodine, iodide, ionic iodine compounds (for example amidotrizoic, trade name: Gastrolux®, Gastrografin®, Peritrast®), non-ionic iodine compounds (for example, compounds having the trade names Ultravist®, Isovist®, Xenetix®), gaseous carbon dioxide (CO₂), Titanium oxide and zirconium oxide.

p0029The above object is further achieved by a system comprising a catheter having a balloon and an implant, said implant described above, and the implant is positioned on the balloon of the catheter. Such a system is well suited for insertion of the implant with the above advantages for the treatment in an organism.

p0030The above object is also achieved by a method for producing an implant comprising the steps of:<ul><li>o providing a base structure having a plurality of through openings,</li><li>o applying a coating, which in the dilated state of at least 20% of the cross-sectional area, preferably at least 50% of the cross-sectional area, at least a portion of the openings of a predetermined portion of the base structure, preferably the openings of the predetermined section with the smallest area, covered and comprising at least one pharmaceutically active substance releases.</li></ul>

p0031The specified method of the invention is a simple method for producing an implant according to the invention.

p0032As discussed above, the coating is preferably applied such that at most every second of the juxtaposed, through holes of the predetermined section with the at least one pharmaceutically active substance-releasing coating is covered. Particularly preferably, the coating is applied such that at most 95% of the total cross-sectional areas of all openings of the predetermined portion in the dilated state with at least one pharmaceutically active substance releasing coating covers or spans.

p0033It is further advantageous if the coating is applied by dipping, Dipping, Spraying, pipetting or the like, said not to be coated areas may be protected by a masking and / or a cover.

p0034In a preferred embodiment of the manufacturing method of the invention the coating is first applied, then are preferably placed in a stretched condition of the coating into the coating pores or broken open pores and during or after the introduction or disruption of the pores, the at least one active pharmaceutical substance in the pores introduced. Hereby is achieved that the pharmaceutically active substance is released in particular only after the dilatation of the implant from the coating. Furthermore, can be easily controlled, the direction in which the delivery of a pharmaceutically active substance is carried out at least.

p0035The above object is also achieved by a method for producing a system comprising a catheter and an implant, wherein firstly the implant is prepared as indicated above, and then the implant on the catheter, preferably on the balloon of the catheter, mounted, for example crimped, is , This production process is inexpensive.

p0036The inventive method and the inventive implant and the system according to the invention are explained in examples with reference to figures. All of the described and / or illustrated form the subject matter of the invention, irrespective of their summary in the claims or their references.

p0037Schematically:<dl id="dl0001"><dt>figure 1</dt><dd>a portion of a first Anführungsbeispiels a erfindungsgenäßen implant in a view from the side</dd><dt>figure 2</dt><dd>a portion of a second embodiment of an inventive implant in a view from the side, </dd><dt>figure 3</dt><dd>a portion of a third embodiment of an inventive implant in a view from the side,</dd><dt>figure 4</dt><dd>a portion of a fourth embodiment of an inventive implant, also in a view from the side,</dd><dt>figure 5</dt><dd>a section of a cell of an inventive implant with coating in a view from the side,</dd><dt>figure 6</dt><dd>a portion of a fifth embodiment of an inventive implant in a view from the side in a non-dilated state (<figref idrefs="f0006">6a</figref>)) And in a dilated state (<figref idrefs="f0006">figure 6b</figref>)) as</dd><dt>figure 7</dt><dd>a cross section through a cell in the <figref idrefs="f0005">figure 5</figref> Embodiment of an implant according to the invention shown.</dd></dl>

p0038The in <figref idrefs="f0001">figure 1</figref> Section shown a basic structure of a hollow cylindrical stent has straight, extending in the longitudinal direction of the webs 2 and S-shaped curved webs 3 which run on the lateral surface perpendicular to the longitudinal direction. Between each two extending longitudinally webs 2 and two S-shaped curved webs 3 two curved ridges 5 are arranged, which together form a substantially keyhole-shaped, through opening. 7 The extending longitudinally webs 2 are arranged only in every second, longitudinally extending row of formed by the webs 5 stitches. The two, the keyhole-shaped opening 7 forming webs 5 a stitch or cell is formed. In addition, six curved webs form 5, two opposite, straight webs 2 and four S-shaped curved ridges 3 together form a mesh or cell with an H-shaped opening 8 from. The cross-sectional area of ​​the keyhole-shaped opening 7 is smaller than the cross sectional area of ​​the H-shaped opening eighth

p0039The keyhole shaped openings 7 are covered about 70% of its cross-sectional area with a least one pharmaceutically active substance containing coating.

p0040The coating consists of a matrix material, in particular rubber, latex, PLLA (Poly-L-lactide), PLGA (poly-L-glycolide) or PBMA (poly-butyl methacrylate) or a shape memory polymer. The coating further comprises one or more pharmaceutically active substance (s), preferably paclitaxel or sirolimus on. The release of the pharmaceutically active substance (s) is carried out by flushing by body fluid.

p0041In the <figref idrefs="f0001">figure 1</figref> Coating shown has two parts, a first part 11 at the head end and a second part 12 at the foot not spans each keyhole-shaped opening 7. The H-shaped openings 8 are of a coating. In this design of the coating, it is possible to vary by the design variable, and the filling density and the amount of drug concentration.

p0042The basic structure of the stent with the webs 2, 3 and 5 is preferably made of the CoCr alloy metal, or, in a particularly preferred embodiment, from a biodegradable magnesium alloy.

p0043In the in <figref idrefs="f0002">FIG. 2</figref> Illustrated embodiment, 100% of the cross sectional area of ​​each keyhole-shaped opening 7 is covered with a coating 10th In addition to the key-hole shaped openings 7 contains the basic structure of the stent or H-shaped openings, which, however, analogous to that in<figref idrefs="f0001">Fig. 1</figref> embodiment shown are not provided with a coating comprising the pharmaceutically active substance, is covered.

p0044Also in the embodiment in <figref idrefs="f0003">Fig. 3</figref> is shown, the cross-sectional area defined by the approximately oval openings 7 'is formed, to 100% with the coating 10' covers. The intervening, by the webs 2, 3 'and 5' formed approximately H-shaped openings 8 'are each provided with no coating.

p0045In <figref idrefs="f0004">Fig. 4</figref> is a basic structure of a stent according to the invention shown, which has an approximately circular meshes "are formed. Each of approximately circular cross-sectional area of ​​the opening 7" by bent fins 5 of the mesh is completely coated with the coating 10 'covers.

p0046The approximately circular loops are connected by transverse to the longitudinal direction webs 3 'together. In the direction of the longitudinal direction of the stent, no separate webs are arranged in this embodiment. The by the webs 3 'and the webs 5 "trained, H-shaped mesh 8" have no coating.

p0047<figref idrefs="f0005">Fig. 5</figref> shows the portion of a web 15, which forms a loop or cell of the basic structure of an inventive implant, in a view from the luminal direction. This ridge is covered with a least one pharmaceutically active substance containing coating 20, spanning each one formed by the web 15 through opening 27th In the<figref idrefs="f0005">Figures 5a) and 5b</figref>) Are each represented portions of the same mesh, said in <figref idrefs="f0005">Fig. 5a</figref>) Illustrated web 15 with coating 20 is part of a non-dilated implant, while the web 15, which in <figref idrefs="f0005">Fig. 5b</figref>) Is shown, has been dilated with the appropriate implant. The coating 20 is resilient so that they can occupy both states, without tearing.

p0048In <figref idrefs="f0006">Fig. 6</figref> is another embodiment of an inventive implant shown that essentially the basis <figref idrefs="f0002">FIG. 2</figref> Illustrated embodiment corresponds. In contrast to the second embodiment, the keyhole-shaped openings are arranged in opposite directions. Further, the coating 10 is approximately along a center line has a dotted line of perforations 22 which in the non-dilated state (see<figref idrefs="f0006">Fig. 6a</figref>)), However, still is closed, and represents a predetermined breaking line. Along the perforation line 22 spaced holes in the coating 10 are spaced apart and / or the coating has a slightly smaller 10 layer thickness. During dilatation of the implant of the assembly to the treatment site in the body, the elongation of the coating 10 is so strong that the perforation line 22 tears open, and an opening 24 is formed. The opening 24 is enclosed by edges 23 which extend along the above, ie in the non-dilated state, the present perforation 22nd The rupture of the coating 10 along a predetermined line of perforations 22 during dilatation has the advantage that on the one hand, an opening 24 is created in the coating 10 at a defined location. On the other hand, the release of the contained in the coating 10 the pharmaceutically active substance (s) is facilitated by the tearing open of the coating 10th

p0049<figref idrefs="f0007">Fig. 7</figref> shows that in <figref idrefs="f0005">Fig. 5</figref> already illustrated embodiment in a cross section. The anchoring of the coating 20 takes place by means lasered grooves (slots) 17 which are disposed on the abluminal surface 16 of the respective web 15th Here, the coating 20 is fixed by means of a form fit and / or by means of an adhesive not shown (adhesive bond) into the grooves 17th Alternatively, take place without groove a material connection between the coating 20 and bridge 15th In<figref idrefs="f0005">Fig. 5</figref> is the profile of the ground line 18 of the triangular cross-section groove 17 illustrated as a dotted line.

p0050The in <figref idrefs="f0001 f0002 f0003 f0004 f0005 f0006">Figures 1-6</figref> illustrated coating 10, 10 ', 10', 11, 12 and 20 serves as a preferably highly elastic support one or more pharmaceutically active substances. These substances may, for example, during the preparation of the coating solution already by immersion or diffusion into the solution and therefore in the future polymer be introduced. Furthermore, additional X-ray markers or radiopaque materials in the coating can be provided. This can for example by means of trapped particles, Diving, diffusion, sputtering, electrochemical or static deposition, possibly with subsequent heat treatment for introducing or fixing, or in the layer the layer material. embedded.

p0051The coating is applied by dipping, spraying, pipetting or the like, wherein the non surfaces to be coated are protected by a mask, a hydrophobic coating and / or a cover.

p0052In one embodiment, all not to coated surfaces or recesses (open spaces) are provided with a cover and / or a hydrophobic protective layer. Thereafter, the implant is coated by dipping or dipping for producing the at least one pharmaceutically active substance-releasing coating. When the coating is carried out in this step on all sides, in particular the luminal side of the stent is covered. Here, the coating material does not adhere to the surfaces of the stent, which were provided with the cover or protective layer. Following then the covers or protective layers are removed by heating, stripping or etching. Here, the hydrophobic protective layer remain on the ridges when it is executed biocompatible.

p0053In principle, it is ensured that the coating becomes attached not only on the lands, but target specific openings or a certain area of ​​certain openings spanned by the coating is produced by targeted pipetting, if not all openings are to be coated. This ensures that, as in<figref idrefs="f0007">Fig. 7</figref> shown, all holding areas are used. After curing, the matrix can be deliberately introduced flaws in certain areas of the coating. Suitable methods would be, for example, laser cutting, or cutting -punktieren. In another embodiment, also so-called predetermined breaking points can be punched or rolled in the coating. In dilatation coating tears then exactly one at this point.

p0054In the coating also shape memory polymers may be used. First element or building block for a shape memory polymer, all materials can be used, from which polymers can be prepared. It is further preferred that these materials are biocompatible. The second element for producing a shape memory material causes the programming to which the plastic is brought into its second, temporary shape. After the preparation of the polymer for a specific field of application this is processed classical. Here, the material is once melted and cooled. So the plastic gets its first permanent shape. The material is then heated again, via its so-called switching temperature addition. This switching temperature is derived from the specific properties of the material and is based on a phase transition of the polymer chains, which is well below the initial processing temperature. The plastic is thereby deformed a second time, again cooled to below the switching temperature, and thereby "programmed", that is fixed in its second temporary shape. In this form, the coating is then brought to its operating. There the material gets its specific thermal stimulus, for example, the body temperature of the treated

p0055Organism or a warm liquid which is brought to the polymer via a probe. By this stimulus, the polymer decreases at the treatment site back to its first permanent shape. Said shape memory polymers (FGP) are therefore particularly well suited to accommodate a pharmaceutically active substance in various forms and those at the treatment site and releasing it again, as provided in these polymers pores ( "programmed") can be, dilatation only after can rise at the implant again and release the active compound. The introduction of the pharmaceutically active substance is carried out during or after the "Programming". Examples of polymers with shape memory effect are multi-block copolymers or standard polymers (PET, PS, PU, ​​PE, PES, PTFE). The hardcoding for example, by briefly heating the shape memory polymer to the shape memory temperature to give aufdehnt the polymer. In this phase, pores can break or be introduced by means of stamping or etching. Now the drug may be filled into the pores, for example by diffusion.

p0056The maximum thickness of the coating is preferably 100 microns. At a layer thickness of more than 100 microns, the required elasticity of the coating is not ensured.

p0057The implants of the invention are characterized in that a large area for the release of a pharmaceutically active substance is created. This enables a more uniform distribution of the active ingredient in the treated area of ​​the institution. The dosage of the active compounds can thus be increased. Furthermore, the distribution of the coating at different portions of the implant is different Artwork, for example, different to the proximal or distal end of the implant.

LIST OF REFERENCE NUMBERS

p0058<dl id="dl0002"><dt>2</dt><dd>web </dd><dt>3, 3 '</dt><dd>web</dd><dt>5, 5 ', 5 "</dt><dd>web</dd><dt>7</dt><dd>keyhole-shaped opening</dd><dt>7 '</dt><dd>oval opening</dd><dt>7 "</dt><dd>circular opening</dd><dt>8, 8 ', 8 "</dt><dd>H-shaped opening</dd><dt>10, 10 ', 10 "</dt><dd>coating</dd><dt>11</dt><dd>coating</dd><dt>12</dt><dd>coating</dd><dt>15</dt><dd>web</dd><dt>16</dt><dd>abluminal side</dd><dt>17</dt><dd>groove</dd><dt>18</dt><dd>bottom line</dd><dt>20</dt><dd>coating</dd><dt>22</dt><dd>perforation</dd><dt>23</dt><dd>edge</dd><dt>24</dt><dd>opening</dd><dt>27</dt><dd>opening</dd></dl>