Device for in vivo delivery of bioactive agents and method of manufacture thereof

Abstract

The implantable structural element for in vivo controlled delivery of bioactive active agents to a situs in a body. The implantable structural element may be configured as an implantable prosthesis, such as an endoluminal stent, cardiac valve, osteal implant or the like, which serves a dual function of being prosthetic and a carrier for a bioactive agent. Control over elution of the bioactive agents occurs through a plurality of cantilever-like cover members which prevent drug elution until an endogenous or exogenous stimulus causes the cover members to open and permit drug elution.

What is claimed is: 
     
         1 . An implantable drug-eluting medical device, comprising:
 a body member comprising a wall surface that delineates the body member from its environment, a repository for a bioactive agent, and an opening between the repository and the environment; and   a cover member;   wherein the wall surface defines a contour and the cover member deviates from the contour, and the repository is paired with the cover member.   
     
     
         2 . The device of  claim 1 , wherein the body member includes more than one repository and more than one cover member. 
     
     
         3 . The device of  claim 2 , wherein a first pairing of repository and cover member exhibits differential drug delivery characteristics relative to a second pairing of repository and cover member. 
     
     
         4 . The device of  claim 1 , wherein the bioactive agent comprises one or more pharmacologically active compounds. 
     
     
         5 . The device of  claim 1 , wherein the body member is formed from a metallic film. 
     
     
         6 . The device of  claim 5 , wherein the device is a stent comprising a plurality of body members defining a plurality of struts. 
     
     
         7 . The device of  claim 5 , wherein the device is a stent comprising a plurality of body members defining one or more circumferential rings. 
     
     
         8 . The device of  claim 1 , wherein the body member is fabricated from a biocompatible metal. 
     
     
         9 . The device of  claim 8 , wherein the body member is fabricated from a metal selected from the group consisting of titanium, vanadium, aluminum, nickel, tantalum, zirconium, chromium, silver, gold, silicon, magnesium, niobium, scandium, platinum, cobalt, palladium, manganese, molybdenum and alloys thereof, such as zirconium-titanium-tantalum alloys, nickel-titanium alloy, chromium-cobalt alloy or stainless steel. 
     
     
         10 . An endoluminal stent, comprising:
 a tubular member having a central lumen passing longitudinally through the tubular member and open at opposing ends of the tubular member, a luminal surface and an abluminal surface and a wall thickness defined therebetween,   a plurality of internal cavities enclosed within the wall thickness in portions of the tubular member that are substantially isolated from stress or strain forces on the endoluminal stent during delivery and deployment,   a plurality of openings communicating between the at least one internal cavity and at least one of the luminal surface, abluminal surface, proximal end or distal end of the tubular member, and at least one bioactive agent disposed in the at least one internal cavity.   
     
     
         11 . The endoluminal stent according to  claim 10 , wherein the tubular member further comprises a material selected from the group consisting of titanium, vanadium, aluminum, nickel, tantalum, zirconium, chromium, silver, gold, silicon, magnesium, niobium, scandium, platinum, cobalt, palladium, manganese, molybdenum and alloys thereof, zirconium-titanium-tantalum alloys, nitinol, and stainless steel. 
     
     
         12 . The endoluminal stent according to  claim 11 , wherein the bioactive agent further comprises a pharmacologically active agent selected from the group of antibiotic drugs, antiviral drugs, neoplastic agents, steroids, fibronectin, anti-clotting drugs, anti-platelet function drugs, drugs which prevent smooth muscle cell growth on inner surface wall of vessel, heparin, heparin fragments, aspirin, coumadin, tissue plasminogen activator, urokinase, hirudin, streptokinase, antiproliferatives selected from the group of methotrexate, cisplatin, fluorouracil and adriamycin), antioxidants selected from the group of ascorbic acid, beta carotene and vitamin E, antimetabolites, thromboxane inhibitors, non-steroidal and steroidal anti-inflammatory drugs, immunosuppresents, rapamycin, beta and calcium channel blockers, genetic materials including DNA and RNA fragments, complete expression genes, antibodies, lymphokines, growth factors, vascular endothelial growth factor, fibroblast growth factor, prostaglandins, leukotrienes, laminin, elastin, collagen, nitric oxide, and integrins. 
     
     
         13 . A drug eluting stent, comprising:
 a plurality of metal strut members interconnected by a plurality of hinge regions, each of the plurality of strut members having an intermediate region between adjacent hinge regions, the intermediate region being subject to relatively lower stress or strain forces than the hinge regions;   a metal covering layer disposed over at least some of the plurality of strut members and covering the intermediate region of the strut members, the covering layer having an inverted generally U-shape, such that the metal covering layer and the intermediate region of each strut member defines an internal cavity therebetween;   a plurality of openings formed in and passing through the metal covering layer and communicating between the internal cavity and external the metal covering layer; and   at least one bioactive agent disposed in the each internal cavity, the at least one bioactive agent capable of being released from within the at least one internal cavity through the at least one of a plurality of openings.   
     
     
         14 . The stent according to  claim 13 , wherein the metal strut members and the metal covering layer are each comprises of a material selected from the group consisting of titanium, vanadium, aluminum, nickel, tantalum, zirconium, chromium, silver, gold, silicon, magnesium, niobium, scandium, platinum, cobalt, palladium, manganese, molybdenum and alloys thereof, zirconium-titanium-tantalum alloys, nitinol, and stainless steel. 
     
     
         15 . The stent according to  claim 13 , wherein the bioactive agent further comprises a pharmacologically active agent selected from the group of hydrophobic pharmacologically active agents, hydrophilic pharmacologically active agents, antibiotic drugs, antiviral drugs, neoplastic agents, steroids, fibronectin, anti-clotting drugs, anti-platelet function drugs, drugs which prevent smooth muscle cell growth on inner surface wall of vessel, heparin, heparin fragments, aspirin, coumadin, tissue plasminogen activator, urokinase, hirudin, streptokinase, antiproliferatives, antioxidants, antimetabolites, thromboxane inhibitors, non-steroidal and steroidal anti-inflammatory drugs, immunosuppresents, rapamycin, beta and calcium channel blockers, genetic materials including DNA and RNA fragments, complete expression genes, antibodies, lymphokines, growth factors, prostaglandins, leukotrienes, laminin, elastin, collagen, nitric oxide, and integrins.