Polymeric coating for reducing the rate of release of a therapeutic substance from a stent

Abstract

A stent for delivery of a therapeutic agent is disclosed. The stent includes a polymer coating for reducing the rate of release of the therapeutic agent. The polymer has a crystalline structure wherein the polymer is capable of significantly maintaining the crystalline lattice structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline lattice structure of the polymer to an amorphous structure.

1 . A stent for delivery of a therapeutic agent, comprising: 
 a substrate; and    a polymer coating on the substrate having a first coating layer, a second coating layer, and a third coating layer,    wherein the third coating layer is over the second coating layer and the second coating layer is over the first coating layer,    wherein the first coating layer is a reservoir layer containing a therapeutic agent above the substrate, the second coating layer is free from therapeutic agents, and the third coating layer increases the biocompatibility of the device, and    wherein the third coating layer includes a polymer selected from a group consisting of ethylene vinyl alcohol, polyethylene glycol, and hyaluronic acid,    the polymer in the second coating layer being capable of substantially reducing the rate of release of the therapeutic agent, wherein the polymer in the second coating layer has a crystalline structure and is capable of significantly maintaining the crystalline structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the polymer of the second layer to an amorphous structure.    
     
     
         2 . The stent of  claim 1 , wherein the polymer in the first coating layer is capable of substantially reducing the rate of release of the therapeutic agent, wherein the polymer in the first coating layer has a crystalline structure and is capable of significantly maintaining the crystalline structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the polymer of the second layer to an amorphous structure.  
     
     
         3 . The stent of  claim 1 , wherein the polymer in the second coating layer and optionally the first coating layer is selected from a group consisting of fluoroethylene-alkyl vinyl ether copolymer, polyhexafluoropropene, low density linear polyethylenes having high molecular weights, ethylene-olefin copolymers, styrene-ethylene-styrene block copolymers, styrene-butylene-styrene block copolymers, styrene-ethylene/butylene-styrene block copolymers, styrene-butadiene-styrene block copolymers, ethylene-anhydride copolymers, ethylene-acrylic acid copolymers, styrenic block copolymers, ethylene methacrylic acid copolymers, polyurethanes with a polydimethylsiloxane soft segment, poly(vinylidene fluoride-co-hexafluoropropene), polycarbonate urethanes, and nylon 6.  
     
     
         4 . A method of forming a coating for a stent that substantially reduces the rate of release of a therapeutic agent from the stent, comprising: 
 applying a first composition including a first polymeric material to at least a portion of the stent to form a first polymer coating layer supported by the stent,    applying a second composition including a second polymeric material over at least a portion of the first coating layer to form a second polymer coating layer over the first coating layer,    applying a third composition including a third polymeric material over at least a portion of the second coating layer to form a third polymer coating layer over the second coating layer, the third polymer coating layer increasing the biocompatibility of the device,    the second polymeric material having a crystalline structure, wherein the aqueous environment to which the second coating layer is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the second polymeric material to an amorphous structure for the duration of time which the agent is released from the coating layers,    the third polymeric material in the third polymer coating layer is selected from a group consisting of ethylene vinyl alcohol, polyethylene glycol, and hyaluronic acid.    
     
     
         5 . The method of  claim 4 , wherein the first polymeric material has a crystalline structure, and wherein the aqueous environment to which the first coating layer is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the first polymeric material to an amorphous structure for the duration of time which the agent is released from the coating layers.  
     
     
         6 . The method of  claim 4 , wherein the polymeric material in the first coating layer and the second coating layer is selected from a group consisting of fluoroethylene-alkyl vinyl ether copolymer, polyhexafluoropropene, low density linear polyethylenes having high molecular weights, ethylene-olefin copolymers, styrene-ethylene-styrene block copolymers, styrene-butylene-styrene block copolymers, styrene-ethylene/butylene-styrene block copolymers, styrene-butadiene-styrene block copolymers, ethylene-anhydride copolymers, ethylene-acrylic acid copolymers, styrenic block copolymers, ethylene methacrylic acid copolymers, polyurethanes with a polydimethylsiloxane soft segment, poly(vinylidene fluoride-co-hexafluoropropene), polycarbonate urethanes, and nylon 6.  
     
     
         7 . A stent for delivering a therapeutic agent to an implanted site, comprising: 
 a radially expandable body structure; and    a polymeric coating supported by the body structure that substantially increases the residence time of the therapeutic agent at the implanted site,    wherein the polymeric coating includes a first coating layer, a second coating layer, and a third coating layer,    wherein the third coating layer is over the second coating layer, the second coating layer is over a first coating layer, the first coating layer is a reservoir layer containing a therapeutic agent above the substrate, the second coating layer is free from therapeutic agents, and the third coating layer increases the biocompatibility of the device,    wherein the second coating layer is made from a hydrophobic polymer having a degree of crystallinity that remains at or above about 10% at least until a significant amount of the therapeutic substance has been released from the stent, and    wherein the third coating layer includes a polymer selected from a group consisting of ethylene vinyl alcohol, polyethylene glycol, and hyaluronic acid.    
     
     
         8 . The stent of  claim 7 , wherein the first coating layer is made from a hydrophobic polymer having a degree of crystallinity that remains at or above about 10% at least until a significant amount of the therapeutic substance has been released from the stent.  
     
     
         9 . The stent of  claim 7 , wherein the polymer in the second coating layer and the first coating layer is selected from a group consisting of fluoroethylene-alkyl vinyl ether copolymer, polyhexafluoropropene, low density linear polyethylenes having high molecular weights, ethylene-olefin copolymers, styrene-ethylene-styrene block copolymers, styrene-butylene-styrene block copolymers, styrene-ethylene/butylene-styrene block copolymers, styrene-butadiene-styrene block copolymers, ethylene-anhydride copolymers, ethylene-acrylic acid copolymers, styrenic block copolymers, ethylene methacrylic acid copolymers, polyurethanes with a polydimethylsiloxane soft segment, poly(vinylidene fluoride-co-hexafluoropropene), polycarbonate urethanes, and nylon 6.