Patent EA-003260-B1 (EA)
Title: Implant with cavities containing therapeutic agents
Inventor: BRANDAU WOLFGANG
IPC: A61F2/82
Filed: 1999-11-02
Abstract: 1. An implant (1), comprising a support (2), in particular of metal, and with at least one therapeutic agent (5), and an at least partially formed covering layer (6) for contacting at least one of body tissue and/or body liquids, the covering layer having a plurality of cavities (10) formed by electrolytic oxidization with separate openings (9) open to the surface (8) of the covering layer (6) for absorbing the at least one therapeutic agent (5), wherein the covering layer (6) substantially consisting of a material selected from the group of electrolytically oxidized aluminium oxide, magnesium oxide, tantalum oxide, iron oxide and/or tungsten oxide, the openings (9) having an average diameter of a maximum of 100 nm. 2. The implant according to claim 1, wherein the covering layer (6), comprises at least an essentially uniform thickness of at most 1.5 mum, preferably at most 200 nm and, in particular, 30 to 150 nm. 3. The implant according to 1 or 2, wherein the covering layer (6) forms a barrier layer (11) impermeable, in particular, for body fluids, and which covers almost the whole surface (7) of the support (2). 4. The implant according to one the preceding claims, wherein the cavities (10) essentially homogeneously formed, formed at least essentially longitudinally, tube-like cavities, being closed at least on one side, 5. The implant according to one of the preceding claims, wherein the cavities (10) extending at least essentially parallel to each other. 6. The implant according to any one of claims 1 to 4, wherein the cavities (10) extending at least essentially perpendicularly to the surfaces (7, 8) of one of the covering layer (6) and/or the support (2). 7. The implant according to one of the preceding claims, wherein any of the cavities (10) having one of different sections, sections with varying cross-sections, and/or branched sections. 8. The implant according to one of the preceding claims, wherein the openings (9) are distributed with a surface density of 10<8> to 10<11>pcs/cm<-2> over the surface (8) of the covering layer (6). 9. The implant according to one of the preceding claims, wherein the sum of the cross-sectional opening areas of the area of the openings (9) is at most 50% of the surface (8) of the covering layer (6). 10. The implant according to one of the preceding claims, wherein the openings (9) having at least essentially the same minimum and/or maximum diameter. 11. The implant according to one of the preceding claims, wherein the cavities (10) have a cross-section with a diameter of maximum at most 100 nm, preferably at most 50 nm, in particular 25 nm or less. 12. The implant according to one of the preceding claims, wherein the openings (9) have an opening area with an average diameter at most 50 nm, in particular 25 nm or less. 13. The implant according to one of the preceding claims, wherein the implant is a stent. 14. The implant according to one of the preceding claims, wherein the therapeutic agent (5) is fixed or bound chemically, at least partly to walls (12) of the cavities (10), in particular, by complexing agents (13). 15. The implant according to one of the preceding claims, wherein the therapeutic agent (5) is fixed or bound chemically in the cavities for release from the implant (1) in the implanted condition upon a factor selected from the group of a temperature above a predetermined temperature, presence of body-specific substances, body fluids, enzymes or activation substances, and other activation factors, in particular laser or ultrasound. 16. The implant according to one of the preceding claims, wherein includes at least two therapeutic agents absorbed in the cavities such that the agents are releasable in a manner selected from the group of release in succession, release with a different rate, and release in a different amount in the implanted condition. 17. The implant according to one of the preceding claims, wherein the implant includes radioactive material as therapeutic agent (5) which contains a predetermined amount of at least one radionuclide. 18. The implant according to claim 17, wherein the radioactive material is bound chemically to walls (12) of the cavities (10) via complexing agents (13) such as thiols. 19. The implant according to claim 17 or 18, wherein the radioactive material containing radioactive rhenium and/or technetium, fixed in the cavities via sulphur groups. 20. The implant according to claims 17 to 19, wherein the radioactive material includes various radionuclides in respectively predetermined amounts and ratios, and differing in at least one of half-life, type of radiation and energy. 21. The implant according to one of the preceding claims, wherein the covering layer (6) or the openings (9) are closed or covered by an upper cover layer (14), preferably made of gold, at least before its separation from the covering layer (6) surface or dissolving in a body. 22. Method for producing an implant according to one of claims 1 to 21, including the steps of placing the implant (1) under reduced pressure for evacuating the cavities (10); introducing the therapeutic agent (5) and/or the binder (13) into the cavities via the openings (9) fixing therapeutic agent (5) in the cavities (10), in particular by dipping the implant (1) into the therapeutic agent (5) and/or a binder (13) and returning the pressure to normal. 23. Method for producing an implant according to one of claims 1 to 21, wherein introducing the therapeutic agent (5) and/or the binder (13) into the cavities by means of ultrasound, in particular, when the implant (1) is dipped into the therapeutic agent (5) and/or a binder (13). 24. Method for producing an implant according to one of claims 1 to 21, wherein including the steps of at least partly coating the cavity (10) walls (12) with one of complexing agents (13) and reaction partners for chemically binding the therapeutic agent (5) and subsequently incorporating the therapeutic agent (5) into the cavities (10) via the openings (9). 25. Method for producing an implant according to claim 24, wherein radioactive material as a therapeutic agent (5) is fixed in the cavities (10) via formation of one of complexes and/or chemical bonds and/or covering the openings (9) or the covering layer (6) by an upper cover layer (14) made, for example, of gold. 25. Use of an implant according to one of claims 1 to 21 for introducing into the cavities (10) a required amount of the therapeutic agent (5), fixing it in the cavities (10) and/or releasing it in the implanted condition under the predetermined conditions with a desired release rate.