Coated devices and methods of making coated devices that reduce smooth muscle cell proliferation and platelet activity

Abstract

The present invention relates generally to the maintenance of blow flood using drug eluting stents and/or other coated medical devices to increased length of time of blood flow. Further, the present invention relates to drug-releasing coated devices for reducing smooth muscle cell proliferation and platelet activity to further limit restenosis utilizing resveratrol and quercetin, polyphenols that are linked to the cardioprotection of red wine consumption. The present invention also provides products and methods for treating or preventing atherosclerosis, stenosis, restenosis, smooth muscle cell proliferation, platelet cell activation and other clotting mechanisms, occlusive disease, or other abnormal lumenal cellular proliferation condition in a location within the body of a patient.

1 - 68 . (canceled) 
     
     
         69 . A drug eluting intravascular stent comprising:
 (a) a generally cylindrical stent body;   (b) an adherent layer coating on the stent comprising a composite of a first active agent selected from the group consisting of resveratrol, pharmaceutically acceptable salts thereof, and pharmaceutically acceptable derivatives thereof, and a second active agent selected from the group consisting of quercetin, pharmaceutically acceptable salts thereof, and pharmaceutically acceptable derivatives thereof, wherein said first and second active agent are dispersed within the polymer.   
     
     
         70 . The stent according to  claim 69 , wherein the stent body has a metal surface. 
     
     
         71 . The stent according to  claim 69 , wherein the stent body is micro- or nanoporous. 
     
     
         72 . The stent according to  claim 69 , wherein the stent body has a polymeric surface. 
     
     
         73 . The stent of  claim 69  wherein the composite includes a polymer and the active ingredients are one of on a polymer layer and in the polymer layer. 
     
     
         74 . The stent according to  claim 73 , wherein the polymer is a bioabsorbable polymer. 
     
     
         75 . The stent according to  claim 73 , wherein the polymer is a biostable polymer. 
     
     
         76 . The stent according to  claim 69 , wherein a weight of the first active agent and a weight of the second active agent are in a ratio which is selected from the group consisting of about 1:1, about 1:2, about 2:1, about 1:2.5, about 2.5:1, about 1:4, about 4:1, about 1:5, about 5:1, about 1:10, about 10:1, about 1:20, about 20:1, about 1:25, about 25:1, about 1:50, about 50:1, about 1:100, about 100:1, about 1:200, about 200:1, about 1:250, about 250:1, about 1:500, and about 500:1. 
     
     
         77 . The stent according to  claim 69 , wherein a weight of the first active agent and a weight of the second active agent are in a ratio which is selected from the group consisting of about 1:5, about 1:2, and about 1:1. 
     
     
         78 . The stent of  claim 69  wherein the composite includes a polymer selected from the group consisting of polystyrene-polyisobutylene block copolymers, polyethylene terephthalate, poly(lactide), poly(lactide-co-glycolide), poly(caprolactone), poly(lactide-co-caprolactone), poly(-hydroxybutyrate/hydroxyvalerate) copolymer, poly(vinylpyrrolidone), polytetrafluoroethylene, poly(2-hydroxyethylmethacrylate), poly(n-butyl methacrylate), poly(ethylene-co-vinyl acetate), poly(vinylidene fluoride-co-hexafluoropropene), poly(etherurethane urea), silicones, acrylics, epoxides, polyesters, polyurethanes, desaminotyrosine polyarylate, Parylenes [polyxylylenes], polyphosphazene polymers, fluoropolymers, polyamides, isoolefin homopolymers and copolymers, vinyl homopolymers and copolymers, acrylate homopolymers and copolymers, methacrylate homopolymers and copolymers, polyethers, polyesters polycarbonates and copolymers, polyethylene oxides, poly(ethylene glycol) and derivatives, carbo-films, self-assembling polymer films and liposomes cellulosics, chondroitin-sulfate, gelatin, amino acid-based polymers, fibrin, chitin, extracellular matrix proteins, heparinized coatings, phospholipid liposomes and self-assembled arrays, poly lactides and mixtures thereof. 
     
     
         79 . The stent according to  claim 73  wherein
 a first weight comprises a combined weight of the first and second active agents; 
 a second weight comprises a weight of the polymer; and 
 the first weight and the second weight are in a ratio selected form the group consisting of about 1:1, about 1:2, about 2:1, about 1:2.5, about 2.5:1, about 1:4, about 4:1, about 1:5, about 5:1, about 1:10, about 10:1, about 1:20, about 20:1, about 1:25, about 25:1, about 1:50, about 50:1, about 1:100, about 100:1, about 1:200, about 200:1, about 1:250, about 250:1, about 1:500, and about 500:1. 
 
     
     
         80 . The stent according to  claim 69 , wherein the composite includes a plurality of layers. 
     
     
         81 . The stent according to  claim 73 , wherein the composite includes a plurality of layers and a ratio of pharmaceutically active agents to polymer is varied in some of the layers. 
     
     
         82 . The stent of  claim 69  wherein at least one active agent is selected from agents which treat or prevent atherosclerosis, stenosis, restenosis, smooth muscle cell proliferation, platelet cell activation and other clotting mechanisms, occlusive disease, or other abnormal lumenal cellular proliferation condition within a body of a patient. 
     
     
         83 . The stent of  claim 69 , wherein the concentration of the first active agent based on the surface area of the stent ranges from about 1 to about 5 μg/mm 2 , and the concentration of the second active agent based on the surface area of the stent ranges from about 1 to 5 μg/mm 2 . 
     
     
         84 . The stent of  claim 69 , wherein each of the active agents have release profiles selected from the group consisting of the same release profile and different release profiles. 
     
     
         85 . The stent of  claim 69 , wherein the active agents have a release profile which is selected from the group consisting of a rapid release profile and a delayed release profile. 
     
     
         86 . The stent of  claim 69 , wherein a rapid profile coating releases at least one of the active agents substantially within one to a few hours. 
     
     
         87 . The stent of  claim 69 , wherein a delayed profile coating releases at least one of the active agents over a period of at least one month, at least two months, at least six months, or at least one year. 
     
     
         88 . The stent of  claim 69 , wherein the composite comprises a single layer.