Additive able to provide underwater adhesion

Abstract

Compositions and methods for sealing tissue of a patient in a wet environment are disclosed.

1 . A compound comprising a polymer core substituted with at least one L-3,4-dihydroxyphenylalanine (L-DOPA) group and at least one sulfhydryl-reactive group. 
     
     
         2 . The compound of  claim 1 , wherein the polymer core is selected from the group consisting of branched polyethylene glycols (PEG), branched poly(ethylene oxide)-poly(propylene oxide) copolymers, branched polyglycerols, branched propylene glycols, poly(oxyalkylene)-substituted diols, poly (mono-, di- and tri-polyoxyethylated) glycerols, poly (mono- and di-polyoxyethylated) propylene glycols, and poly (mono- and di-polyoxyethylated) trimethylene glycols, polyoxyethylated sorbitols, polyoxyethylated glucoses, polymethacrylic acid, poly(hydroxyethylmethacrylates), poly(hydroxyethylacrylates), poly(methylalkylsulfoxide methacrylates), poly(methylalkylsulfoxide acrylates), polymaleic acid; poly(acrylamides), poly(methacrylamides), poly(dimethylacrylamides), poly(N-isopropyl-acrylamides), and copolymers thereof; poly(vinyl alcohols) and copolymers thereof, poly(vinyl pyrrolidones), poly(N-vinyl caprolactams), and copolymers thereof, kpoly(methyloxazoline), poly(ethyloxazoline), polyvinylamines, and copolymers thereof. 
     
     
         3 . The compound of  claim 1 , wherein the polymer core is branched poly(ethylene oxide). 
     
     
         4 . The compound of  claim 1 , wherein the polymer core is a 4-arm poly(ethylene oxide), a 6-arm poly(ethylene oxide), or an 8-arm poly(ethylene oxide). 
     
     
         5 . The compound of  claim 1 , wherein the sulfhydryl-reactive group is selected from the group consisting of mixed anhydrides, ester derivatives of phosphorus, ester derivatives of p-nitrophenol, ester derivatives of p-nitrothiophenol, ester derivatives of pentafluorophenol, N-hydroxyphthalimide esters, N-hydroxy-succinimide esters, N-hydroxysulfosuccinimide esters, N-hydroxyglutarimide esters, esters of 1-hydroxybenzotriazole, esters of 3-hydroxy-3,4-dihydro-benzotriazin-4-one, esters of 3-hydroxy-3,4-dihydro-quinazoline-4-one, carbonylimidazole derivatives, acid chlorides, ketenes, isocyanates, maleimides, substituted maleimides, haloalkanes, epoxides, imines, aziridines; ethenesulfonyl, etheneimino, acrylate, methacrylate, α,β-unsaturated aldehydes, α,β-unsaturated ketones; and combinations thereof. 
     
     
         6 . The compound of  claim 1 , wherein the sulfhydryl-reactive group is a succinimidyl group, an acrylate group, or a vinyl sulfone. 
     
     
         7 . The compound of  claim 1 , wherein the compound has a structure of Formula I: 
       
         
           
           
               
               
           
         
         wherein: 
         each R is independently a sulfhydryl-reactive group or OH 
       
       
         
           
           
               
               
           
         
         L is null, —(CH 2 ) 1-5 —, —CO(CH 2 ) 1-5 —, —NHCO(CH 2 ) 1-5 —, —(CH 2 ) 1-5 NHCO(CH 2 ) 1-5 —; and 
         each n is independently 15 to 150; 
         provided that at least one R group is 
       
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 7 , wherein L is —CO(CH 2 ) 3 — or —NHCO(CH 2 ) 2 —. 
     
     
         9 . The compound of  claim 7 , wherein the sulfhydryl-reactive group is 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 1 , wherein the compound has a structure of Formula II or Formula III: 
       
         
           
           
               
               
           
         
         wherein 
         each R is independently a sulfhydryl-reactive group or 
       
       
         
           
           
               
               
           
         
         L is null, —(CH 2 ) 1-5 —, —CO(CH 2 ) 1-5 —, —NHCO(CH 2 ) 1-5 —, or —(CH 2 ) 1-5 NHCO(CH 2 ) 1-5 —; and 
         each n is independently 15 to 150; 
         provided that at least one R group is 
       
       
         
           
           
               
               
           
         
       
     
     
         11 . The compound of  claim 10 , wherein L is —CO(CH 2 ) 2 —, —CO(CH 2 ) 3 —, or —(CH 2 ) 2 NHCO(CH 2 ) 2 —. 
     
     
         12 . The compound of  claim 10 , wherein the sulfhydryl-reactive group is 
       
         
           
           
               
               
           
         
       
     
     
         13 . A dry powder composition comprising (i) a component having a polymer core substituted with at least two sulfhydryl groups and (ii) the compound of  claim 1 . 
     
     
         14 . The dry powder composition of  claim 13 , further comprising a component having a polymer core substituted with at least two sulfhydryl-reactive groups. 
     
     
         15 . A solution composition comprising (i) a component having a polymer core substituted with at least two sulfhydryl groups and (ii) the compound of  claim 1 , wherein the solution has a pH of about 1 to about 5.5. 
     
     
         16 . The solution composition of  claim 15 , further comprising a component having a polymer core substituted with at least two sulfhydryl-reactive groups. 
     
     
         17 . A composition prepared by reacting a first component having a first polymer core substituted with at least two sulfhydryl groups with (i) a second component having a second polymer core substituted with at least two sulfhydryl-reactive groups and (ii) the compound of  claim 1 . 
     
     
         18 . A method of sealing tissue of a patient comprising:
 (a) dissolving a dry powder composition comprising (i) a first component having a polymer core substituted with at least two sulfhydryl groups, (ii) a second component having a polymer core substituted with at least two sulfhydryl-reactive groups, and (iii) a third component comprising a polymer core substituted with at least one L-3,4-dihydroxyphenylalanine (L-DOPA) group and at least one sulfhydryl-reactive group in a first aqueous solution having a pH of about 1 to about 5.5 to form a homogeneous solution;   (b) adding a second aqueous solution having a pH of about 6 to about 11 to the homogeneous solution to form a mixture; and   (c) placing the mixture into contact with a tissue surface and allowing a three-dimensional composition to form on the tissue.   
     
     
         19 . The method of  claim 18 , wherein the polymer core is selected from the group consisting of branched polyethylene glycols (PEG), branched poly(ethylene oxide)-poly(propylene oxide) copolymers, branched polyglycerols, branched propylene glycols, poly(oxyalkylene)-substituted diols, poly (mono-, di- and tri-polyoxyethylated) glycerols, poly (mono- and di-polyoxyethylated) propylene glycols, and poly (mono- and di-polyoxyethylated) trimethylene glycols, polyoxyethylated sorbitols, polyoxyethylated glucoses, polymethacrylic acid, poly(hydroxyethylmethacrylates), poly(hydroxyethylacrylates), poly(methylalkylsulfoxide methacrylates), poly(methylalkylsulfoxide acrylates), polymaleic acid; poly(acrylamides), poly(methacrylamides), poly(dimethylacrylamides), poly(N-isopropyl-acrylamides), and copolymers thereof; poly(vinyl alcohols) and copolymers thereof, poly(vinyl pyrrolidones), poly(N-vinyl caprolactams), and copolymers thereof, kpoly(methyloxazoline), poly(ethyloxazoline), polyvinylamines, and copolymers thereof. 
     
     
         20 . The method of  claim 19 , wherein the polymer core is branched poly(ethylene oxide). 
     
     
         21 . The method of  claim 19 , wherein the polymer core is a 4-arm poly(ethylene oxide), a 6-arm poly(ethylene oxide), or an 8-arm poly(ethylene oxide). 
     
     
         22 . The method of  claim 18 , wherein the sulfhydryl-reactive group is selected from the group consisting of mixed anhydrides, ester derivatives of phosphorus, ester derivatives of p-nitrophenol, ester derivatives of p-nitrothiophenol, ester derivatives of pentafluorophenol, N-hydroxyphthalimide esters, N-hydroxy-succinimide esters, N-hydroxysulfosuccinimide esters, N-hydroxyglutarimide esters, esters of 1-hydroxybenzotriazole, esters of 3-hydroxy-3,4-dihydro-benzotriazin-4-one, esters of 3-hydroxy-3,4-dihydro-quinazoline-4-one, carbonylimidazole derivatives, acid chlorides, ketenes, isocyanates, maleimides, substituted maleimides, haloalkanes, epoxides, imines, aziridines; ethenesulfonyl, etheneimino, acrylate, methacrylate, α,β-unsaturated aldehydes, α,β-unsaturated ketones, and combinations thereof. 
     
     
         23 . The method of  claim 18 , wherein the sulfhydryl-reactive group is a succinimidyl group, an acrylate group, or a vinyl sulfone.