Coating for implantable devices and a method of forming the same

Abstract

Coatings for implantable devices or endoluminal prosthesis, such as stents, are provided, including a method of forming the coatings. The coatings can be used for the delivery of an active ingredient or a combination of active ingredients.

1 . An implantable device comprising a coating, wherein the coating comprises: 
 a) a reservoir region comprising a polymer and a drug blended with or dispersed in the polymer; and    b) a primer region free from any drugs located between the reservoir region and the surface of the device, the primer region comprising a material selected from a group consisting of polyisocyanates, unsaturated polymers, high amine content polymers, acrylates, polymers containing a high content of hydrogen bonding groups, inorganic polymers, and any combination thereof.    
   
   
       2 . The implantable device of  claim 1 , wherein the device is a stent.  
   
   
       3 . The implantable device of  Claim 1 , wherein the surface of the device includes a chromium oxide layer.  
   
   
       4 . The implantable device of  claim 1 , wherein the polyisocyanates are selected from triisocyanurate, alphatic polyisocyanate resins based on hexamethylene diisocyanate, aromatic polyisocyanate prepolymers based on diphenylmethane diisocyanate, polyisocyanate polyether polyurethanes based on diphenylmethane diisocyanate, polymeric isocyanates based on toluene diisocyanate, polymethylene polyphenyl isocyanate, polyester polyurethanes, and any combination thereof.  
   
   
       5 . The implantable device of  claim 1 , wherein the unsaturated polymers are selected from polyester diacrylates, polycaprolactone diacrylates, polytetramethylene glycol diacrylate, polyacrylates with at least two acrylate groups, polyacrylated polyurethanes, triacrylates, and any combination thereof.  
   
   
       6 . The implantable device of  claim 1 , wherein the amine content polymers are selected from polyethyleneamine, polyallylamine, polylysine, and any combination thereof.  
   
   
       7 . The implantable device of  claim 1 , wherein the acrylates are selected from copolymers of ethyl acrylate, methyl acrylate, butyl methacrylate, methacrylic acid, acrylic acid, cyanoacrylates, and any combination thereof.  
   
   
       8 . The implantable device of  claim 1 , wherein the polymers containing 15 hydrogen bonding groups are selected from polyethylene-co-polyvinyl alcohol, epoxy polymers based on the diglycidylether of bisphenol A with amine crosslinking agents, epoxy polymers cured by polyols and Lewis acid catalysts, epoxy phenolics, epoxy-polysulfides, ethylene vinyl acetate, melamine formaldehydes, polyvinylalcohol-co-vinyl acetate polymers, resorcinol-formaldehydes, urea-formaldehydes, polyvinylbutyral, polyvinylacetate, alkyd polyester resins, acrylic acid modified ethylene vinyl acetate polymers, methacrylic acid modified ethylene vinyl acetate polymers, acrylic acid modified ethylene acrylate polymers, methacrylic acid modified ethylene acrylate polymers, anhydride modified ethylene acrylate copolymers, anhydride modified ethylene vinyl acetate polymers, and any combination thereof.  
   
   
       9 . The implantable device of  claim 1 , wherein the inorganic polymers are selected from silane coupling agents, titanates, zirconates, and any combination thereof.  
   
   
       10 . The implantable device of  claim 9 , wherein the silane coupling agents are selected from 3-aminopropyltriethoxysilane, (3-glydidoxypropyl) methyldiethoxysilane, and any combination thereof.  
   
   
       11 . The implantable device of  claim 9 , wherein the titanates are selected from tetra-iso-propyl titanate, tetra-n-butyl titanate, or any combination thereof.  
   
   
       12 . The implantable device of  claim 9 , wherein the zirconates are selected from n-propyl zirconate, n-butyl zirconate, or any combination thereof.  
   
   
       13 . The implantable device of  claim 9 , wherein the surface is metallic.  
   
   
       14 . The implantable device of  claim 9 , wherein the reservoir region includes a combination of polymers.  
   
   
       15 . An implantable device comprising 
 a) a substrate having a surface, wherein the surface includes a chromium oxide layer;    b) a primer layer free from drugs deposited on the surface, the primer layer including a polymeric material with polar substituents or cationic groups; and    c) a reservoir layer comprising polymer and a drug deposited on the primer layer.    
   
   
       16 . The implantable device of  claim 15 , wherein the polymeric material of the primer layer is selected from a group consisting of polyisocyanates, unsaturated polymers, high amine content polymers, acrylates, polymers containing a high content of hydrogen bonding groups, inorganic polymers, and any combination thereof.  
   
   
       17 . An implantable device comprising a coating, wherein the coating comprises: 
 a) a reservoir region comprising a polymer and a drug; and    b) a primer region free from any drugs located under the reservoir region and on the surface of the device, the primer region comprising a material selected from a group consisting of poly(hydroxyvalerate), poly(L-lactic acid), polycaprolactone, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoesters, polyanhydrides, poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoesters, polyphosphoester urethanes, poly(amino acids), cyanoacrylates, poly(trimethylene carbonates), poly(iminocarbonate), copoly(ether-esters), polyalkylene oxalates, polyphosphazenes, fibrin, fibrinogen, cellulose, starch, collagen, hyaluronic acid, polyurethanes, silicones, polyesters, polyolefins, polyisobutylene, ethylene-alphaolefin copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers, polyvinyl chloride, polyvinyl ethers, polyvinyl methyl ether, polyvinylidene halides, polyvinylidene fluoride, polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics, polystyrene, polyvinyl esters, polyvinyl acetate, copolymers of vinyl monomers with each other and olefins, ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, ethylene-vinyl acetate copolymers, polyamides, Nylon 66, polycaprolactam, alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, epoxy resins, rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, and combinations or blends thereof.    
   
   
       18 . An stent comprising a coating, wherein the coating comprises: 
 a) a reservoir region comprising a drug; and    b) a primer region free from any drugs located between the reservoir region and the surface of the stent, the coating including a material selected from a group consisting of polyisocyanates, unsaturated polymers, high amine content polymers, acrylates, polymers containing a high content of hydrogen bonding groups, inorganic polymers, and any combination thereof.    
   
   
       19 . The implantable device of  claim 18 , wherein the polyisocyanates are selected from triisocyanurate, alphatic polyisocyanate resins based on hexamethylene diisocyanate, aromatic polyisocyanate prepolymers based on diphenylmethane diisocyanate, polyisocyanate polyether polyurethanes based on diphenylmethane diisocyanate, polymeric isocyanates based on toluene diisocyanate, polymethylene polyphenyl isocyanate, polyester polyurethanes, and any combination thereof.  
   
   
       20 . The implantable device of  claim 18 , wherein the unsaturated polymers are selected from polyester diacrylates, polycaprolactone diacrylates, polytetramethylene glycol diacrylate, polyacrylates with at least two acrylate groups, polyacrylated polyurethanes, triacrylates, and any combination thereof.  
   
   
       21 . The implantable device of  claim 18 , wherein the amine content polymers are selected from polyethyleneamine, polyallylamine, polylysine and any combination thereof.  
   
   
       22 . The implantable device of  claim 18 , wherein the acrylates are selected from copolymers of ethyl acrylate, methyl acrylate, butyl methacrylate, methacrylic acid, acrylic acid, cyanoacrylates, and any combination thereof.  
   
   
       23 . The implantable device of  claim 18 , wherein the polymers containing hydrogen bonding groups are selected from polyethylene-co-polyvinyl alcohol, epoxy polymers based on the diglycidylether of bisphenol A with amine crosslinking agents, epoxy polymers cured by polyols and Lewis acid catalysts, epoxy phenolics, epoxy-polysulfides, ethylene vinyl acetate, melamine formaldehydes, polyvinylalcohol-co-vinyl acetate polymers, resorcinol-formaldehydes, urea-formaldehydes, polyvinylbutyral, polyvinylacetate, alkyd polyester resins, acrylic acid modified ethylene vinyl acetate polymers, methacrylic acid modified ethylene vinyl acetate polymers, acrylic acid modified ethylene acrylate polymers, methacrylic acid modified ethylene acrylate polymers, anhydride modified ethylene acrylate copolymers, anhydride modified ethylene vinyl acetate polymers, and any combination thereof.  
   
   
       24 . The implantable device of  claim 18 , wherein the inorganic polymers are selected from silane coupling agents, titanates, zirconates, and any combination thereof.  
   
   
       25 . The implantable device of  claim 24 , wherein the silane coupling agents are selected from 3-aminopropyltriethoxysilane, (3-glydidoxypropyl) methyldiethoxysilane, and any combination thereof.  
   
   
       26 . The implantable device of  claim 24 , wherein the titanates are selected from tetra-iso-propyl titanate, tetra-n-butyl titanate, and any combination thereof.  
   
   
       27 . The implantable device of  claim 24 , wherein the zirconates are selected from n-propyl zirconate, n-butyl zirconate, and any combination thereof.  
   
   
       28 . An stent comprising: 
 a) a substrate having oxide, anionic, or hydroxyl moieties or groups on the outer surface thereof;    b) a primer region free from any drugs disposed on the outer surface of the substrate, the primer region including a polymer with polar substituents or cationic groups; and    c) a reservoir region comprising a drug disposed over the primer region.