Processes for producing polymer coatings through surface polymerization

Abstract

A medical device with a therapeutic agent-releasing polymer coating. The medical device is provided by a method that comprises: (a) attaching at least one reactive species to a medical device surface, which reactive species leads to chain growth polymerization in the presence of monomer; (b) contacting the reactive species with at least one monomer species, thereby forming a polymer coating on the surface of the medical device; and (c) providing at least one therapeutic agent within the polymer coating. The therapeutic agent may be incorporated during formation of the polymer coating or after formation of the polymer coating. The at least one reactive species can comprise, for example, a free radical species, a carbanion species, a carbocation species, a Ziegler-Natta polymerization complex, a metallocene complex, and/or an atom transfer radical polymerization initiator. Alternatively, the medical device is provided by a process comprising: (a) immobilizing least one polymerization catalyst at a medical device surface, which polymerization catalyst leads to polymerization in the presence of monomer; (b) contacting the medical device surface with at least one monomer species, thereby forming a polymer coating at the surface of the medical device; and (c) providing at least one therapeutic agent within the polymer coating.

In the claims:  
     
         1 . A method of providing a medical device with a therapeutic agent-releasing polymer coating comprising: 
 (a) attaching at least one reactive species to a medical device surface, said reactive species leading to chain growth polymerization in the presence of monomer;    (b) contacting said reactive species with at least one monomer species, thereby forming a polymer coating on the surface of the medical device; and    (c) providing at least one therapeutic agent within said polymer coating.    
     
     
         2 . The method of  claim 1 , wherein at least one therapeutic agent is incorporated during formation of the polymer coating.  
     
     
         3 . The method of  claim 1 , wherein at least one therapeutic agent is incorporated after formation of the polymer coating.  
     
     
         4 . The method of  claim 1 , wherein the medical device is an implantable or insertable medical device.  
     
     
         5 . The method of  claim 4 , wherein the medical device is a stent.  
     
     
         6 . An implantable or insertable medical device made by the method of  claim 1 .  
     
     
         7 . The method of  claim 1 , wherein said at least one monomer species comprises an unsaturated monomer.  
     
     
         8 . The method of  claim 1 , wherein said polymer is selected from polyalkylenes and derivatives, vinyl polymers and derivatives, acrylic acid polymers and derivatives, and copolymers thereof.  
     
     
         9 . The method of  claim 1 , wherein said polymer is selected from ethylene vinyl acetate and styrene-isobutylene copolymers.  
     
     
         10 . The method of  claim 1 , wherein said at least one reactive species comprises a free radical species.  
     
     
         11 . The method of  claim 10 , wherein the free radical species is provided by a process comprising (a) covalently attaching a free-radical initiator molecule to the surface or (b) covalently attaching a species that acquires a free-radical upon exposure to a free radical initiator molecule.  
     
     
         12 . The method of  claim 1 , wherein said at least one reactive species comprises a carbanion species.  
     
     
         13 . The method of  claim 12 , wherein the carbanion species is provided by a process comprising (a) covalently attaching an anionic initiator molecule to the surface or (b) covalently attaching a species that acquires a carbanion upon exposure to an anionic initiator molecule.  
     
     
         14 . The method of  claim 1 , wherein said at least one reactive species comprises a carbocation species.  
     
     
         15 . The method of  claim 14 , wherein the carbocation species is provided by a process comprising covalently attaching a species that develops a carbocation upon exposure to a cationic initiator molecule.  
     
     
         16 . The method of  claim 1 , wherein said at least one reactive species comprise a Ziegler-Natta polymerization complex.  
     
     
         17 . The method of  claim 1 , wherein said at least one reactive species comprises a metallocene complex.  
     
     
         18 . The method of  claim 1 , wherein said at least one reactive species comprises an atom transfer radical polymerization initiator.  
     
     
         19 . The method of  claim 18 , wherein the at least one reactive species is provided by a process comprising (a) covalently attaching an atom transfer radical polymerization initiator molecule to the surface or (b) covalently attaching a species that acquires a free-radical upon exposure to an atom transfer radical polymerization initiator and an atom transfer radical polymerization catalyst.  
     
     
         20 . The method of  claim 1 , wherein the at least one reactive species is formed from a derivatized monomer that is covalently bonded to the surface of the medical device.  
     
     
         21 . The method of  claim 1 , wherein the at least one reactive species is formed from a derivatized initiator compound that is covalently bonded to the surface of the medical device.  
     
     
         22 . A method of providing a medical device with a therapeutic agent-releasing coating comprising: 
 (a) immobilizing least one polymerization catalyst at a medical device surface, said polymerization catalyst leading to polymerization in the presence of monomer;    (b) contacting the medical device surface with at least one monomer species, thereby forming a polymer coating at the medical device surface; and    (c) providing at least one therapeutic agent within said polymer coating.    
     
     
         23 . The method of  claim 22 , wherein the at least one polymerization catalyst is immobilized by covalently bonding it to said surface.  
     
     
         24 . The method of  claim 22 , wherein the at least one polymerization catalyst is immobilized by physically embedding it in said surface.  
     
     
         25 . The method of  claim 22 , wherein the medical device surface is at least partially covered by a metal catalyst.  
     
     
         26 . The method of  claim 22 , further comprising cross-linking said polymer coating.  
     
     
         27 . The method of  claim 22 , wherein the at least one monomer species comprises a dendrimer.  
     
     
         28 . The method of  claim 22 , wherein at least one therapeutic agent is provided within the polymer coating during formation of the polymer coating.  
     
     
         29 . The method of  claim 22 , wherein at least one therapeutic agent is provided within the polymer coating after formation of the polymer coating.  
     
     
         30 . The method of  claim 22 , wherein the medical device is an implantable or insertable medical device.  
     
     
         31 . The method of  claim 30 , wherein the medical device is a stent.  
     
     
         32 . An implantable or insertable medical device made by the method of  claim 22 .  
     
     
         33 . The method of  claim 22 , wherein said polymer is selected from ethylene vinyl acetate copolymers, poly(ε-caprolactone), styrene-isobutylene copolymers and silicone.