Drug eluting stent with a biodegradable release layer attached with electro-grafted primer coating

Abstract

The present invention provides a drug eluting stent including a metallic stent framework, an electro-grafted primer coating disposed on the stent framework; and a biodegradable polymer coating hosting a drug disposed on the electro-grafted primer coating and a method of manufacturing said biodegradable drug eluting stent.

1 . A drug eluting stent for implantation comprising:
 a stent framework;   a drug hosting biodegradable polymer coating, wherein the drug inhibit or prevent vascular restenosis and wherein the biodegradable polymer is degraded to completely release the drug after the stent implantation and the stent is fully recolonized by endothelial cells within 8 weeks.   
     
     
         2 . The drug eluting stent of  claim 1 , wherein the stent framework has a surface with a layer that promotes proliferation and adhesion of the endothelial cells to ensure the full recolonization of the stent by endothelial cells and wherein the drug hosting biodegradable polymer coating covers that surface. 
     
     
         3 . The drug eluting stent of  claim 2 , wherein the layer is a polymeric layer. 
     
     
         4 . The drug eluting stent of  claim 3 , wherein the polymeric layer is a polymer or a co-polymer obtained by electro-grafting. 
     
     
         5 . The drug eluting stent of  claim 4 , wherein the electro-grafted layer is biodegradable or non-biodegradable. 
     
     
         6 . The drug eluting stent of  claim 5 , wherein the electro-grafted layer is made from monomers chosen from the group consisting of vinylics, epoxides and cyclic monomers undergoing ring opening polymerisation, aryl diazonium salts, butyl methacrylate, methyl methacrylate, hydroxyethyl methacrylate, 2-methacryloyloxyethyl phosphorylcholine (MPC), dodecyl methacrylate (DMA), trimethylsilylpropylmethacrylate (TMSPA), lactic acid, epsilon caprolactone and 4-aminophenyl diazonium tetrafluoro borate. 
     
     
         7 . The drug eluting stent of any one of  claims 4 , wherein the electro-grafted layer has a thickness between 10 nanometers and 1.0 micrometers. 
     
     
         8 . The drug eluting stent of  claim 1 , wherein the drug hosting biodegradable polymer coating is selected from the group consisting of one or more biodegradable polymers, copolymers, and block polymers. 
     
     
         9 . The drug eluting stent of  claim 1 , wherein the biodegradable polymer is selected from the group consisting of polyglycolides, polylactides, polycaprolactones, polyglycerol sebacate, polycarbonates, biopolyesters, polyethylene oxide, polybutylene terepthalate, polydioxanones, hybrids, composites, collagen matrices with growth modulators, proteoglycans, glycosaminoglycans, vacuum formed small intestinal submucosa, fibers, chitin, dextran and mixtures. 
     
     
         10 . The drug eluting stent of  claim 1 , wherein the biodegradable polymer is poly-lactide-co-glycoside. 
     
     
         11 . The drug eluting stent of  claim 1 , wherein the drug hosting biodegradable polymer coating has a thickness between 1 and 200 microns. 
     
     
         12 . The drug eluting stent of  claim 11 , wherein the drug hosting biodegradable polymer coating has a thickness between 1 and 10 microns. 
     
     
         13 . The drug eluting stent of  claim 1 , wherein the biodegradable polymer coating is degraded to completely release the drug within 4 weeks after the stent implantation. 
     
     
         14 . The drug eluting stent of  claim 1 , wherein the biodegradable polymer coating is degraded within 4 weeks after the stent implantation. 
     
     
         15 . The drug eluting stent of  claim 1 , wherein the stent is fully recolonized by endothelial cells within 28 days 
     
     
         16 . The drug eluting stent of  claim 1 , wherein the stent is fully recolonized by endothelial cells within 8 weeks in a porcine coronary artery model. 
     
     
         17 . The drug eluting stent of  claim 1 , further comprising a biodegradable topcoat layer. 
     
     
         18 . The drug eluting stent of  claim 17 , wherein the topcoat layer is made from the same composition as that of the drug hosting biodegradable polymer based coating. 
     
     
         19 . The drug eluting stent of  claim 1 , wherein the stent framework comprises a metallic base. 
     
     
         20 . The drug eluting stent of  claim 19 , wherein the metallic base is made of at least one material selected from a group consisting of stainless steel, nitinol, tantalum, cobalt chromium alloys like MP35N or MP20N, platinum, titanium, a suitable biocompatible alloy, a suitable biocompatible material, and a combination thereof. 
     
     
         21 . The drug eluting stent of  claim 1 , wherein the polymer coating hosts a bioactive agent. 
     
     
         22 . The drug eluting stent of  claim 21 , wherein, the bioactive agent is selected from the group consisting of an antisense agent, an antineoplastic agent, an antiproliferative agent, an antithrombogenic agent, an anticoagulant, an antiplatelet agent, an antibiotic, an anti-inflammatory agent, a gene therapy agent, a therapeutic substance, an organic drug, a pharmaceutical compound, a recombinant DNA product, a recombinant RNA product, a collagen, a collagenic derivative, a protein, a protein analog, a saccharide, and a saccharide derivative. 
     
     
         23 . The drug eluting stent of  claim 1 , wherein the drugs are encapsulated in a drug polymer coating using a microbead, microparticle or nanoencapsulation technology with albumin, liposome, ferritin or other biodegradable proteins and phospholipids, prior to application on the primer-coated stent.