Bioabsorbable coating with tunable hydrophobicity

Abstract

The present invention relates to implantable medical devices coated with polymer having tunable hydrophobicity and their use in the treatment of vascular diseases.

1 .- 29 . (canceled) 
     
     
         30 . An implantable medical device, comprising:
 a polymer and one or more therapeutic agents, wherein the hydrophobicity of the polymer is matched to that of the therapeutic agent(s),   wherein the polymer is a copolymer comprising a first monomer selected from the group consisting of L-lactide, D-lactide, D,L-lactide and meso-lactide and a second monomer selected from the group consisting of lactone, ε-caprolactone, δ-valerolactone, 1,4-dioxan-2-one, 1,5-dioxepan-2-one, 1,4,6-trioxaspiro[4.4]nonane and trimethyl carbonate, wherein
 the first monomer, the second monomer, or both are optionally substituted with a moiety selected form the group consisting of C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, partially or fully fluorinated derivatives of any of the preceding and combinations thereof so as to match the hydrophobicity of the polymer to that of the therapeutic agent, 
   wherein the therapeutic agent is a mTOR inhibitor.   
     
     
         31 . The implantable medical device of  claim 30 , comprising:
 a drug reservoir layer which comprises the polymer and the one or more therapeutic agents.   
     
     
         32 . The implantable medical device of  claim 30 , wherein the therapeutic agent is everolimus. 
     
     
         33 . The implantable medical device of  claim 30 , wherein the polymer is selected from the group consisting of poly(L-lactide-co-ε-caprolactone) and poly(L-lactide-co-trimethylene carbonate). 
     
     
         34 . The implantable medical device of  claim 33 , wherein the polymer is poly(L-lactide-co-ε-caprolactone) polymer. 
     
     
         35 . The implantable medical device of  claim 34 , wherein the poly(L-lactide-co-ε-caprolactone) constitutional unit molar ratio is from about 70:30 to about 50:50. 
     
     
         36 . The implantable medical device of  claim 34 , wherein the poly(L-lactide-co-ε-caprolactone) has a average molecular weight from about 50,000 to about 500,000 Daltons. 
     
     
         37 . The implantable medical device of  claim 34 , wherein the poly(L-lactide-co-ε-caprolactone) has a solubility parameter less than about 11.5 (cal/cm 3 ) 1/2 . 
     
     
         38 . The implantable medical device of  claim 30 , comprising a drug reservoir layer which comprises the polymer and the one or more therapeutic agents, wherein the drug reservoir layer has a coating thickness from about 1 um to about 10 um. 
     
     
         39 . The implantable medical device of  claim 30 , wherein the drug to polymer wt/wt ratio is from about 1.0:0.5 to about 1.0:10.0. 
     
     
         40 . The implantable medical device of  claim 30 , wherein the drug dose is from about 5-200 microgram/cm 2  or about 20-100 microgram/cm 2 . 
     
     
         41 . The implantable medical device of  claim 30 , wherein the device is a stent, 
     
     
         42 . A method of treating a vascular disease, comprising:
 deploying in the vasculature of a patient in need thereof an implantable medical device, wherein the implantable medical device comprises:   a polymer and one or more therapeutic agents, wherein the hydrophobicity of the polymer is matched to that of the therapeutic agent(s).   wherein the polymer is a copolymer comprising a first monomer selected from the group consisting of L-lactide, D-lactide, D,L-lactide and meso-lactide and a second monomer selected from the group consisting of lactone, ε-caprolactone, 6-valerolactone, 1,4-dioxan-2-one, 1,5-dioxepan-2-one, 1,4,6-trioxaspiro[4.4]nonane and trimethyl carbonate, wherein
 the first monomer, the second monomer, or both are optionally substituted with a moiety selected form the group consisting of C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, partially or fully fluorinated derivatives of any of the preceding and combinations thereof so as to match the hydrophobicity of the polymer to that of the therapeutic agent, 
   wherein the therapeutic agent is a mTOR inhibitor.   
     
     
         43 . The method of  claim 42 , wherein the implantable medical device comprises
 a drug reservoir layer which comprises the polymer and the one or more therapeutic agents.   
     
     
         44 . The method of  claim 42 , wherein the therapeutic agent is everolimus. 
     
     
         45 . The method of  claim 42 , wherein the polymer is selected from the group consisting of poly(L-lactide-co-ε-caprolactone) and poly(L-lactide-co-trimethylene carbonate). 
     
     
         46 . The method of  claim 45 , wherein the polymer is poly(L-lactide-co-ε-caprolactone) polymer. 
     
     
         47 . The method of  claim 46 , wherein the poly(L-lactide-co-ε-caprolactone) constitutional unit molar ratio is from about 70:30 to about 50:50. 
     
     
         48 . The method of  claim 46 , wherein the poly(L-lactide-co-ε-caprolactone) has an average molecular weight from about 50,000 to about 500,000 Daltons. 
     
     
         49 . The method of  claim 46 , wherein the poly(L-lactide-co-ε-caprolactone) has a solubility parameter less than about 11.5 (cal/cm 3 ) 1/2 . 
     
     
         50 . The method of  claim 42 , wherein the implantable medical device comprises a drug reservoir layer which comprises the polymer and the one or more therapeutic agents, and wherein the drug reservoir layer has a coating thickness from about 1 um to about 10 um. 
     
     
         51 . The method of  claim 42 , wherein the drug to polymer wt/wt ratio is from about 1.0:0.5 to about 1.0:10.0. 
     
     
         52 . The method of  claim 42 , wherein the drug dose is from about 5-200 microgram/cm 2  or about 20-100 microgram/cm 2 . 
     
     
         53 . The method of  claim 42 , wherein the implantable medical device is a stent, 
     
     
         54 . The method of  claim 42 , wherein the vascular disease is atherosclerosis, restenosis, vulnerable plaque, peripheral vascular disease, or late stent thrombosis