Coating system and method for drug elution management

Abstract

The teachings are directed to a medical device having a drug-retaining coating that at least substantially delays the initial elution of a drug for a time effective at forming a functional endothelium over a surface of the medical device.

What is claimed: 
     
         1 . A method of forming a therapeutic coating for a medical device comprising:
 forming a drug-containing layer over a surface of a medical device, the drug-containing layer having a drug that functions as an anti-proliferative agent; and   forming a drug-reservoir layer over a surface of the drug-containing layer, the drug reservoir layer comprising a drug retaining layer and an accelerant layer, the drug-retaining layer remaining void or substantially void of the drug at a time of implantation in a subject, and the accelerant layer accelerating the rate of drug elution from the coating;   wherein the drug-containing layer is applied as a solvent mixture and the solvent is dried after application using a substantially non-reactive heated gas to at least substantially inhibit mobilization of the drug from the drug-containing layer during application of additional layers in the formation of the coating;   wherein the drug-reservoir layer comprises at least one sub-layer having a thickness of less than or equal to 3 microns, where a repeated application of the sub-layer is used to form thicknesses of greater than 3 microns;   wherein the accelerant layer is positioned between the drug-containing layer and the remainder of the drug-reservoir layer, is more hydrophilic than the remainder of the drug-reservoir layer, and comprises at least one sub-layer having a thickness of less than or equal to 3 microns, where a repeated application the sub-layer is used to form thicknesses of greater than 3 microns; and   wherein the application of the sub-layers at least substantially promotes a retention of the drug in the drug-containing layer during formation of the coating when compared to such a coating without the application of the sub-layers.   
     
     
         2 . The method of  claim 1 , wherein the medical device comprises a stent. 
     
     
         3 . The method of  claim 1 , wherein the drug-containing layer comprises a poly(lactic-co-glycolic acid), a monomer ratio of lactic acid to glycolic acid ranges from about 85:15 to about 50:50, and a molecular weight ranging from about 110 KDaltons to about 160 KDaltons. 
     
     
         4 . The method of  claim 1 , wherein the drug-retaining layer comprises a poly(lactic-co-glycolic acid) having ester terminal groups, a monomer ratio of lactic acid to glycolic acid ranging from about 85:15 to about 50:50, and a molecular weight ranging from about 90 KDaltons to about 160 KDaltons; and
 wherein the accelerant layer comprises a poly(lactic-co-glycolic acid) with acid terminal groups, a monomer ratio of lactic acid to glycolic acid that ranges from about 85:15 to about 50:50, and a molecular weight that ranges from about 90 KDaltons to about 120 KDaltons.   
     
     
         5 . The method of  claim 1 , wherein the thickness of the coating ranges from about 2 microns to about 9 microns. 
     
     
         6 . The method of  claim 1 , wherein the thickness ratio of the drug-retaining layer to the drug-containing layer ranges from about 4:1 to about 7:1. 
     
     
         7 . The method of  claim 1 , further comprising pockets of hydrophilic material in the drug-retaining layer, wherein the hydrophilic material comprises a component selected from the group consisting of dextran, heparin, ticlopidine, chlopidogrel, enoxaparin, dalteparin, hirudin, bivalirudin, argatroban, and danparoid. 
     
     
         8 . The method of  claim 1 , wherein the drug is selected from the group consisting of:
 fluoroquinolone, paclitaxel, rapamycin, sirolimus, everolimus, biolimus, zotarolimus, tacrolimus, fibroblast growth factor (bFGF), rapamycin analogs, antisense dexamethasone, angiopeptin, BATIMISTAT, tranilast, transilast, halofuginon, acetylsalicylic acid, hirudin, steroids, ibuprofen, antimicrobials, antibiotics, actinomycin D, tissue plasma activators, estradiol, and transcription factor E2F 1.