Medical devices having a surface including a biologically active agent therein

Abstract

The present invention provides a medical device, and methods of preparing and using a medical device. The medical device has a surface including a biologically active agent therein. The methods are particularly useful for preparing, for example, coated stents having a biologically active agent within the coating.

1 - 23 . (canceled) 
   
   
       24 . A medical device prepared by a method comprising:
 applying a coating composition comprising a polymer and a water soluble porogen to at least a portion of a surface of a device;   removing at least a portion of the water soluble porogen to form a porous polymeric coating on at least a portion of the surface of the device;   at least partially loading the porous polymeric coating with a biologically active agent; and   heating at least the porous polymeric coating to at least partially collapse a surface of the porous polymeric coating and encapsulate the biologically active agent.   
   
   
       25 . The medical device of  claim 24  wherein heating completely collapses the porous polymeric coating. 
   
   
       26 . The medical device of  claim 24  wherein the device is selected from the group consisting of stents, grafts, catheters, guide wires, heart valves, bone implants, spinal implants, covered stents, microspheres, and combinations thereof. 
   
   
       27 . The medical device of  claim 24  wherein the medical device is a radially expandable stent. 
   
   
       28 - 48 . (canceled) 
   
   
       49 . A medical device comprising a reformed exposed surface, wherein the reformed exposed surface comprises a biologically active agent encapsulated therein. 
   
   
       50 . The medical device of  claim 49  wherein the reformed exposed surface comprises a porous polymeric surface that has been reformed by heating in air at a temperature of at least about 5° C. above the T g  of a polymer in the porous polymeric surface. 
   
   
       51 . The medical device of  claim 50  wherein the polymer is selected from the group consisting of polycaprolactone (PCL), poly(lactide-co-glycolide) (PLGA), polyvinyl acetate (PVAC), polyvinyl alcohol, copolymers of PCL-PLGA, PLGA-polyethylene glycol (PEG), PCL-PEG, poly L-lactic acid (PLLA)-PEG, cellulose acetate, polyvinylidene chloride (PVDC), polyvinylidene fluoride, polymethyl acrylate, polyhexyl acrylate, polymethyl methacrylate, polyethyl methacrylate, polyhexyl methacrylate, polybutylene methyl acrylate (PBMA), and combinations thereof. 
   
   
       52 . The medical device of  claim 50  wherein the reformed exposed surface comprises an at least partially collapsed porous surface. 
   
   
       53 . The medical device of  claim 52  wherein the reformed exposed surface comprises a completely collapsed porous surface. 
   
   
       54 . The medical device of  claim 49  wherein the medical device is selected from the group consisting of stents, grafts, catheters, guide wires, heart valves, bone implants, spinal implants, covered stents, microspheres, and combinations thereof. 
   
   
       55 . The medical device of  claim 49  wherein the biologically active agent is a drug. 
   
   
       56 . The medical device of  claim 55  wherein the drug is selected from the group consisting of Plasmid DNA, genes, antisense oligonucleotides and other antisense agents, peptides, proteins, protein analogs, siRNA, shRNA, miRNA, ribozymes, DNAzymes and other DNA based agents, viral and non-viral vectors, lyposomes, cells, stem cells, antineoplastic agents, antiproliferative agents, antithrombogenic agents, anticoagulant agents, antiplatelet agents, antibiotics, anti-inflammatory agents, antimitotic agents, immunosuppressants, growth factors, cytokines, hormones, and combinations thereof. 
   
   
       57 . A medical device comprising a reformed polymeric coating on a surface of the device, wherein the reformed polymeric coating comprises a biologically active agent encapsulated therein. 
   
   
       58 . The medical device of  claim 57  wherein the reformed polymeric coating comprises a porous polymeric coating that has been reformed by heating in air at a temperature of at least about 5° C. above the Tg of a polymer in the porous polymeric coating. 
   
   
       59 . The medical device of  claim 58  wherein the polymer is selected from the group consisting of polycaprolactone (PCL), poly(lactide-co-glycolide) (PLGA), polyvinyl acetate (PVAC), polyvinyl alcohol, copolymers of PCL-PLGA, PLGA-polyethylene glycol (PEG), PCL-PEG, poly L-lactic acid (PLLA)-PEG, cellulose acetate, polyvinylidene chloride (PVDC), polyvinylidene fluoride, polymethyl acrylate, polyhexyl acrylate, polymethyl methacrylate, polyethyl methacrylate, polyhexyl methacrylate, polybutylene methyl acrylate (PBMA), and combinations thereof. 
   
   
       60 . The medical device of  claim 58  wherein the reformed polymeric coating comprises an at least partially collapsed porous surface. 
   
   
       61 . The medical device of  claim 60  wherein the reformed polymeric coating comprises a completely collapsed porous polymeric coating. 
   
   
       62 . The medical device of  claim 57  wherein the device is selected from the group consisting of stents, grafts, catheters, guide wires, heart valves, bone implants, spinal implants, covered stents, microspheres, and combinations thereof. 
   
   
       63 . The medical device of  claim 57  wherein the biologically active agent is a drug. 
   
   
       64 . The medical device of  claim 63  wherein the drug is selected from the group consisting of Plasmid DNA, genes, antisense oligonucleotides and other antisense agents, peptides, proteins, protein analogs, siRNA, shRNA, miRNA, ribozymes, DNAzymes and other DNA based agents, viral and non-viral vectors, lyposomes, cells, stem cells, antineoplastic agents, antiproliferative agents, antithrombogenic agents, anticoagulant agents, antiplatelet agents, antibiotics, anti-inflammatory agents, antimitotic agents, immunosuppressants, growth factors, cytokines, hormones, and combinations thereof. 
   
   
       65 . A medical device prepared according to a method comprising:
 providing a device comprising a porous exposed surface, wherein at least a portion of the pores contain a biologically active agent; and   heating at least the porous exposed surface at a temperature of about 30° C. to about 100° C. to at least partially collapse the porous surface and encapsulate the biologically active agent.   
   
   
       66 . A medical device prepared according to a method comprising:
 coating a surface of a device with a porous polymeric coating;   at least partially loading the porous polymeric coating with a biologically active agent; and   heating at least the porous polymeric coating to at least partially collapse a surface of the porous polymeric coating and encapsulate the biologically active agent.   
   
   
       67 . A medical device comprising a partially collapsed polymeric coating on a surface of the device, wherein the polymeric coating comprises a biologically active agent encapsulated therein. 
   
   
       68 . The medical device of  claim 67  wherein the partially collapsed polymeric coating comprises a porous polymeric coating that has been reformed by heating in air at a temperature of at least about 5° C. above the T g  of a polymer in the porous polymeric coating. 
   
   
       69 . The medical device of  claim 68  wherein the polymer is selected from the group consisting of polycaprolactone (PCL), poly(lactide-co-glycolide) (PLGA), polyvinyl acetate (PVAC), polyvinyl alcohol, copolymers of PCL-PLGA, PLGA-polyethylene glycol (PEG), PCL-PEG, poly L-lactic acid (PLLA)-PEG, cellulose acetate, polyvinylidene chloride (PVDC), polyvinylidene fluoride, polymethyl acrylate, polyhexyl acrylate, polymethyl methacrylate, polyethyl methacrylate, polyhexyl methacrylate, polybutylene methyl acrylate (PBMA), and combinations thereof. 
   
   
       70 . The medical device of  claim 67  wherein the medical device is selected from the group consisting of stents, grafts, catheters, guide wires, heart valves, bone implants, spinal implants, covered stents, microspheres, and combinations thereof. 
   
   
       71 . The medical device of  claim 67  wherein the biologically active agent is a drug. 
   
   
       72 . The medical device of  claim 71  wherein the drug is selected from the group consisting of Plasmid DNA, genes, antisense oligonucleotides and other antisense agents, peptides, proteins, protein analogs, siRNA, shRNA, miRNA, ribozymes, DNAzymes and other DNA based agents, viral and non-viral vectors, lyposomes, cells, stem cells, antineoplastic agents, antiproliferative agents, antithrombogenic agents, anticoagulant agents, antiplatelet agents, antibiotics, anti-inflammatory agents, antimitotic agents, immunosuppressants, growth factors, cytokines, hormones, and combinations thereof. 
   
   
       73 . The medical device of  claim 67  wherein the polymeric coating comprises a solvent-sensitive biologically active agent encapsulated therein.