Coatings for implantable devices comprising poly(hydroxy-alkanoates) and diacid linkages

Abstract

Coatings for an implantable medical device and a method of fabricating thereof are disclosed, the coatings including block-polymers comprising at least one poly(hydroxyacid) or poly(hydroxy-alkanoate) block, at least one block of a biologically compatible polymer and at least one type of linking moiety.

1 . A polymer of formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 A are poly(hydroxyacid) or poly(hydroxy-alkanoate) blocks selected from the group consisting of poly(lactide-co-glycolide); poly(L-lactide); poly(D-lactide); poly(D,L-lactide); poly(L-lactide-co-glycolide); poly(D,L-lactide-co-glycolide); poly(L-lactide-co-caprolactone); poly(D,L-lactide-co-caprolactone); poly(L-lactide-co-D,L-lactide); poly(L-lactide-co-trimethylene carbonate); poly(D,L-lactide-co-trimethylene carbonate); poly(L-lactic acid); poly(D-lactic acid); poly(D,L-lactic acid); and a combination thereof; 
 B are blocks of a polymeric biocompatible moiety selected from the group consisting of poly(alkylene glycols), PEG, poly(L-lysine)-graft-co-poly(ethylene glycol), poly(ethylene oxide), poly(propylene glycol) (PPG), poly(tetramethylene glycol), or poly(ethylene oxide-co-propylene oxide); poly(N-vinyl pyrrolidone); poly(acrylamide methyl propane sulfonic acid) and salts thereof; poly(styrene sulfonate); sulfonated dextran; polyphosphazenes; poly(orthoesters); poly(tyrosine carbonate); hyaluronic acid and derivatives thereof, hyaluronic acid having a stearoyl or palmitoyl substituent group, copolymers of PEG with hyaluronic acid or with hyaluronic acid-stearoyl, or with hyaluronic acid-palmitoyl; heparin and derivatives thereof; copolymers of PEG with heparin; or copolymers thereof; poly(2-hydroxyethyl methacrylate); ε-caprolactone; β-butyrolactone; δ-valerolactone; a graft copolymer of poly(L-lysine) and poly(ethylene glycol) and mixtures thereof; glycolide; poly(2-hydroxyethyl methacrylate); poly(3-hydroxypropyl methacrylate); poly(3-hydroxypropyl methacrylamide); and a combination thereof; 
 X is a linking moiety derived from oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, brassylic acid, dodecane-1,12-dicarboxylic acid, tridecane-1,13-dicarboxylic acid, thapsic acid, fumaric acid, maleic acid, 1,3-acetonedicarboxylic acid, or combination thereof; 
 Y is a linking moiety selected from the group consisting of ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol, 1,11-undecanediol, 1,12-dodecanediol, 1,4-cyclohexanedimethanol, 1,4-hydroxymethylbenzene, serinol, dihydroxyacetone, any linear or branched C2 to C12 hydrocarbon with two primary hydroxyl groups, and any linear or branched C2 to C12 with unsaturation and two primary hydroxyl groups, and a combination thereof; and 
 n is an integer between about 2 and about 700. 
 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The polymer of  claim 1  wherein B is one of poly(alkylene glycols), PEG, poly(L-lysine)-graft-co-poly(ethylene glycol), poly(ethylene oxide), polypropylene glycol) (PPG), poly(tetramethylene glycol), or poly(ethylene oxide-co-propylene oxide). 
     
     
         5 - 7 . (canceled) 
     
     
         8 . The polymer of  claim 1  wherein n is about 10. 
     
     
         9 . The polymer of  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
       wherein
 m is between about 2 and about 700; 
 n is between about 2 and about 700; 
 x is between about 5 and about 100; 
 y is between about 2 and about 700; 
 z is between about 2 and about 700; 
 a is between about 5 and about 100; and 
 b is between about 2 and about 700. 
 
     
     
         10 . The polymer of  claim 9  wherein
 m is about 10; 
 n is about 10; 
 x is about 14; 
 y is about 10; 
 z is about 10; 
 a is about 14; and 
 b is about 10. 
 
     
     
         11 - 24 . (canceled) 
     
     
         25 . A coating made with the polymer of  claim 1 . 
     
     
         26 - 28 . (canceled) 
     
     
         29 . A coating made with the polymer of  claim 9 . 
     
     
         30 . A medical device comprising the coating of  claim 25 . 
     
     
         31 - 33 . (canceled) 
     
     
         34 . A medical device comprising the coating of  claim 29 . 
     
     
         35 - 38 . (canceled) 
     
     
         39 . The polymer of  claim 1 , wherein the biologically compatible polymer is: hyaluronic acid or derivatives thereof; hyaluronic acid having a stearoyl or palmitoyl substituent group; copolymers of PEG with hyaluronic acid or with hyaluronic acid-stearoyl, or with hyaluronic acid-palmitoyl; or a combination thereof. 
     
     
         40 . The polymer of  claim 1 , wherein the biologically compatible polymer is poly(N-vinyl pyrrolidone); poly(acrylamide methyl propane sulfonic acid) or salts thereof; poly(styrene sulfonate); sulfonated dextran; polyphosphazenes; poly(orthoesters); poly(tyrosine carbonate); or a combination thereof. 
     
     
         41 . The polymer of  claim 1 , wherein the biologically compatible polymer is heparin or derivatives thereof; copolymers of PEG with heparin, or copolymers thereof; or a combination thereof. 
     
     
         42 . The polymer of  claim 1 , wherein the biologically compatible polymer is poly(2-hydroxyethyl methacrylate); ε-caprolactone; β-butyrolactone; δ-valerolactone; a graft copolymer of poly(L-lysine) and poly(ethylene glycol); glycolide; poly(2-hydroxyethyl methacrylate); poly(3-hydroxypropyl methacrylate); poly(3-hydroxypropyl methacrylamide); or a combination thereof.