Stent coatings with engineered drug release rate

Abstract

Coatings and methods of forming coatings for implantable medical devices, such as stents, are described. The coatings are used for the sustained release of a therapeutic agent or drug.

1 . A stent having a coating, the coating comprising a first region including a thermoplastic polyacrylate material and a therapeutic substance and a second region free from any therapeutic substances disposed on the surface of the stent and beneath the first region, additionally including a third region disposed over the first region, the third region including a thermoplastic polyacrylate material and optionally a therapeutic substance. 
   
   
       2 . A stent having a coating, the coating comprising a first region including a thermoplastic polyacrylate material and a therapeutic substance and a second region free from any therapeutic substances disposed on the surface of the stent and beneath the first region, wherein the first region has a variable thickness along at least a segment of the length of the stent. 
   
   
       3 . A stent having a coating, the coating comprising a first region including a thermoplastic polyacrylate material and a therapeutic substance and a second region free from any therapeutic substances disposed on the surface of the stent and beneath the first region,
 wherein the concentration of the substance is greater in a first area of the first region than in a second area of the first region.   
   
   
       4 . A stent comprising a coating, wherein the coating comprises a first, second, and third layers disposed over one another wherein the second layer includes a thermoplastic polyacrylate material,
 wherein at least one of the layers includes a therapeutic substance,   wherein the first layer is disposed on the outer surface of the stent, and   wherein the third layer comprises a polymer selected from the group consisting of fluorinated polymers, poly(ethylene-co-vinyl alcohol), polydioxanone, poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, polycyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), co-poly(ether-esters), polyalkylene oxalates, polyurethanes, silicones, polyisobutylene, ethylene-alphaolefin copolymers, vinyl halide polymers and copolymers, polyvinyl ethers, polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics, ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, polyamides, alkyd resins, polyoxymethylenes, polyimides, polyethers, epoxy resins, polyurethanes, rayon, rayon-triacetate, fibrin, fibrinogen, cellulose, collagen, hyaluronic acid, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, and carboxymethyl cellulose.   
   
   
       5 . The stent of  claim 4 , wherein the therapeutic substance is contained in the second layer and optionally the third layer but not the first layer. 
   
   
       6 . The stent of  claim 4 , wherein the first layer and the third layer include the therapeutic substance but not the second layer. 
   
   
       7 . The stent of  claim 6 , wherein the first layer is disposed on a primer layer, the primer layer being disposed on the surface of the stent. 
   
   
       8 . The stent of  claim 4 , wherein the first layer includes a polyacrylate material, and wherein at least one of the layers is free from any therapeutic substances. 
   
   
       9 . The stent of  claim 8 , wherein the first layer is disposed on the outer surface of the stent and is free from any therapeutic substances. 
   
   
       10 . A stent comprising a coating containing an active agent or a combination of active agents, the coating having a variable thickness along at least a portion of the length of the stent so as to provide a concentration gradient of the active agent or agents along from a thin region of the coating to the thick region of the coating. 
   
   
       11 . A method of coating a stent comprising forming a coating on the stent, the coating including a first region having a thermoplastic polyacrylate material and a therapeutic substance and a second region free from any therapeutic substances disposed on the surface of the stent beneath the first region,
 wherein the second region comprises a polymer selected from polydioxanone, poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, polycyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), co-poly(ether-esters), polyalkylene oxalates, polyurethanes, silicones, polyisobutylene, ethylene-alphaolefin copolymers, vinyl halide polymers and copolymers, polyvinyl ethers, polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics, ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, polyamides, alkyd resins, polyoxymethylenes, polyimides, polyethers, epoxy resins, polyurethanes, rayon, rayon-triacetate, fibrin, fibrinogen, cellulose, collagen, hyaluronic acid, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, and carboxymethyl cellulose.   
   
   
       12 . A method of coating a stent, comprising forming at least three layers of coating on a stent,
 wherein the second layer includes a thermoplastic polyacrylate material,   wherein at least one of the layers includes a therapeutic substance,   wherein the first layer is disposed on the outer surface of the stent, and   wherein the third layer comprises a polymer selected from the group consisting of fluorinated polymers, poly(ethylene-co-vinyl alcohol), polydioxanone, poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, polycyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), co-poly(ether-esters), polyalkylene oxalates, polyurethanes, silicones, polyisobutylene, ethylene-alphaolefin copolymers, vinyl halide polymers and copolymers, polyvinyl ethers, polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics, ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, polyamides, alkyd resins, polyoxymethylenes, polyimides, polyethers, epoxy resins, polyurethanes, rayon, rayon-triacetate, fibrin, fibrinogen, cellulose, collagen, hyaluronic acid, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, and carboxymethyl cellulose.   
   
   
       13 . A method of coating a stent comprising depositing a coating on the stent wherein the coating has a variable thickness along at least a segment of the length of the stent. 
   
   
       14 . A method of coating a stent, comprising,
 depositing a first layer on the stent, the first layer including a first therapeutic substance;   masking a region of the first layer; and   depositing a second layer on the first layer not covered by the masking layer, the second layer including a second therapeutic substance.