Biobeneficial Coating Compositions And Methods Of Making And Using Thereof

Abstract

A biobeneficial coating composition for coating an implantable device, such as a drug eluting stent, a method of coating the device with the composition, and an implantable device coated with the composition are provided.

What is claimed is: 
     
         1 . A composition for coating an implantable device comprising
 (1) a first block copolymer comprising a block having a glass transition temperature (T g ) below about body temperature and a second block having a T g  or a melting temperature (T m ) above about body temperature, and   (2) a second block copolymer, wherein the second block copolymer comprising
 (i) a biobeneficial component; and 
 (ii) a component selected from the group consisting of components miscible with the first block copolymer and components insoluble in water. 
   
     
     
         2 . The composition of  claim 1 , wherein the block having a T g  above about body temperature has a structure of Formula I and the block having a T g  below about body temperature has a structure of Formula II: 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3  and R 4  are independently hydrogen, phenyl, methyl, ethyl, acrylate, or methacrylate, with the proviso that R 1 , R 2 , R 3  and R 4  cannot all be hydrogen; 
         wherein R 5  and R 7  are independently methyl, ethyl, propyl, butyl, benzyl, or phenyl; and 
         wherein R 6  and R 8  are independently hydrogen, methyl, ethyl, propyl, benzyl, or phenyl. 
       
     
     
         3 . The composition of  claim 1 , wherein the first block copolymer has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The composition of  claim 1 , wherein the second block copolymer is selected from the group consisting of polystyrene-polyisobutylene-polystyrene block copolymer (SIS), polystyrene, polyisobutylene, polycaprolactone (PCL), poly(L-lactide), poly(D,L-lactide), poly(lactides), poly(lactide-co-glycolide), poly(glycolide), polylactic acid (PLA), polyalkylene, polyfluoroalkylene, polyhydroxyalkanoate, poly(3-hydroxybutyrate), poly(4-hydroxybutyrate), poly(3-hydroxyvalerate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3-hydroxyhexanoate), poly(4-hydroxyhexanoate), mid chain polyhydroxyalkanoate, poly (trimethylene carbonate), poly (ortho ester), polyphosphazenes, poly(phosphoester), poly(tyrosine derived arylates), poly(tyrosine derived carbonates), and a combination thereof. 
     
     
         5 . The composition of  claim 1 , wherein the second block copolymer is selected from the group consisting of SIS-PEG, polystyrene-PEG, polyisobutylene-PEG, PCL-PEG, PLA-PEG, PDMS-PEG, PVDF-PEG, SIS-hyaluronic acid (HA), polystyrene-HA, polyisobutylene-HA, PCL-HA, PLA-HA, PMMA-HA, PVDF-HA, SIS-heparin, polystyrene-heparin, polyisobutylene-heparin, PCL-heparin, PLA-heparin, PMMA-heparin, and PVDF-heparin. 
     
     
         6 . The composition of  claim 1 , wherein the component of the second block copolymer miscible with the first block copolymer is a hydrophobic material. 
     
     
         7 . The composition of  claim 1 , wherein the water insoluble component of the second block copolymer is selected from the group consisting of polydimethyloxanone (PDMS), polyvinylidene fluoride (PVDF), polyhexafluoropropylene (HFP), polydimethylsiloxane, poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP), poly(vinylidene fluoride-co-chlorotrifluoroethylene) (PVDF-CTFE), poly(butyl methacrylate), poly(methyl methacrylate), poly(methacrylates), poly(vinyl acetate), poly(ethylene-co-vinyl acetate), poly(ethylene-co-vinyl alcohol), poly(ester urethanes), poly(ether-urethanes), poly(carbonate-urethanes), poly(silicone-urethanes), and poly(urea-urethanes), and a combination thereof. 
     
     
         8 . The composition of  claim 1 , wherein the biobeneficial component of the second block copolymer is selected from the group consisting of poly(ethylene glycol), polypropylene glycol), PLURONIC™ surfactants, poly(tetramethylene glycol), hydroxy functional poly(vinyl pyrrolidone), dextran, dextrin, sodium hyaluronate, hyaluronic acid, heparin, Elastin, Chitosan, poly(2-hydroxyethyl methacrylate), sulphonated poly(styrene), poly(3-hydroxypropyl methacrylamide), 4-amino-2,2′,6,6′-tetrapiperidine oxide, stable nitroxides, super oxide dimutase mimics, free radical scavengers and combinations thereof. 
     
     
         9 . The composition of  claim 1 , further comprising a bioactive agent. 
     
     
         10 . The composition of  claim 9 , wherein the bioactive agent is selected from the group consisting of proteins, peptides, anti-inflammatory agents, antivirals, anticancer drugs, anticoagulant agents, free radical scavengers, and a combination thereof. 
     
     
         11 . The composition of  claim 9 , wherein the bioactive agent is selected from the group consisting of everolimus, sirolimus, sirolimus derivatives, paclitaxel, estradiol, steroidal anti-inflammatory agents, antibiotics, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, ABT-578, clobetasol, cytostatic agents, and a combination thereof. 
     
     
         12 . An implantable device comprising a coating which comprises a composition of  claim 1 . 
     
     
         13 . The implantable device of  claim 12 , wherein the composition further comprising a bioactive agent. 
     
     
         14 . The implantable device of  claim 13 , wherein the bioactive agent is selected from the group consisting of proteins, peptides, anti-inflammatory agents, antivirals, anticancer drugs, anticoagulant agents, and free radical scavengers. 
     
     
         15 . The implantable device of  claim 13 , wherein the bioactive agent is selected from the group consisting of everolimus, sirolimus, sirolimus derivatives, paclitaxel, estradiol, steroidal anti-inflammatory agents, antibiotics, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, ABT-578, clobetasol, cytostatic agents, and a combination thereof. 
     
     
         16 . The implantable device of  claim 12 , which is a stent. 
     
     
         17 . The implantable device of  claim 16 , which is a drug eluting stent (DES).