Methods for tissue repair using adhesive materials
First Claim
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1. A method of repairing damaged tissue in a patient comprising the steps of:
- placing into contact with the damaged tissue an adhesive composition comprised of(i) a hydrophilic polymer;
(ii) a crosslinkable component A having m nucleophilic groups, wherein m≧
2; and
(iii) a crosslinkable component B having n electrophilic groups capable of reaction with the m nucleophilic groups to form covalent bonds, wherein n≧
2 and m+n>
4;
wherein each of components A and B is biocompatible and nonimmunogenic, and at least one of components A and B is hydrophilic polymer, and crosslinking of the composition results in a biocompatible, nonimmunogenic, crosslinked matrix.
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Abstract
A method of tissue repair is provided using a biocompatible nonimmunogenic adhesive composition. The adhesive composition comprises collagen and a plurality of crosslinkable components having reactive functional groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. Kits for use in carrying out the method of the invention are also provided, as are pretreated surgically acceptable patches that have been coated with the aforementioned adhesive composition.
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Citations
53 Claims
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1. A method of repairing damaged tissue in a patient comprising the steps of:
- placing into contact with the damaged tissue an adhesive composition comprised of
(i) a hydrophilic polymer;
(ii) a crosslinkable component A having m nucleophilic groups, wherein m≧
2; and
(iii) a crosslinkable component B having n electrophilic groups capable of reaction with the m nucleophilic groups to form covalent bonds, wherein n≧
2 and m+n>
4;
wherein each of components A and B is biocompatible and nonimmunogenic, and at least one of components A and B is hydrophilic polymer, and crosslinking of the composition results in a biocompatible, nonimmunogenic, crosslinked matrix. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53)
(a) nucleophilic groups capable of reacting with the electrophilic groups of component B and, (b) electrophilic groups capable of reacting with the nucleophilic groups of component, wherein the total number of functional groups on component C is represented by p, such that m+n+p> - 5.
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22. The method of claim 1, wherein component A has the structural formula (I) and component B has the structural formula (II)
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23. The method of claim 21, wherein component C has the structural formula (III)
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24. The method of claim 22, wherein at least one of R1 and R2 is a synthetic hydrophilic polymer.
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25. The method of claim 24, wherein:
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(a) R1 is a first synthetic hydrophilic polymer; and
(b) R2 is selected from the group consisting of (i) a second synthetic hydrophilic polymer that may or may not be the same as R1 and (ii) C2 to C14 hydrocarbyl groups containing zero to 2 heteroatoms selected from N, O and S.
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26. The method of claim 25, wherein the synthetic hydrophilic polymer is of a linear, branched, dendrimeric, hyperbranched, or star polymer.
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27. The method of claim 25, wherein the synthetic hydrophilic polymer is selected from the group consisting of:
- polyalkylene oxides;
polyglycerols;
poly(oxyalkylene)-substituted polyols;
polyacrylic acid and analogs thereof;
polymaleic acid;
polyacrylamides;
poly(olefinic alcohol)s;
poly(N-vinyl lactams);
polyoxazolines;
polyvinylamines; and
copolymers thereof.
- polyalkylene oxides;
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28. The method of claim 27, wherein the synthetic hydrophilic polymer is a polyalkylene oxide or polyglycerol.
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31. The method of claim 27, wherein the synthetic hydrophilic polymer is a poly(oxyalkylene)-substituted diol or polyol.
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32. The method of claim 31, wherein the synthetic hydrophilic polymer is selected from the group consisting of mono-poly(oxyalkylene)-substituted propylene glycol, di-(polyoxyalkylene)-substituted propylene glycol, mono-poly(oxyalkylene)-substituted trimethylene glycol, di-(polyoxyalkylene)-substituted trimethylene glycol, mono-poly(oxyalkylene)-substituted glycerol, di-(polyoxyalkylene)-substituted glycerol, and tri-(polyoxyalkylene)-substituted glycerol.
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33. The method of claim 27, wherein the synthetic hydrophilic polymer is selected from the group consisting of poly(acrylic acid) and analogs and copolymers thereof.
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34. The method of claim 33, wherein the synthetic hydrophilic polymer is selected from the group consisting of poly(acrylic acid), poly(methacrylic acid), poly(hydroxyethylmethacrylate), poly(hydroxyethylacrylate), poly(methylalkylsulfoxide acrylates), poly(methylalkylsulfoxide methacrylates), and copolymers thereof.
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35. The method of claim 27, wherein the synthetic hydrophilic polymer is polymaleic acid.
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36. The method of claim 27, wherein the synthetic hydrophilic polymer is a polyacrylamide.
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37. The method of claim 36, wherein the synthetic hydrophilic polymer is selected from the group consisting of polyacrylamide, poly(methacrylamide), poly(dimethylacrylamide), poly(N-isopropylacrylamide), and copolymers thereof.
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38. The method of claim 27, wherein the synthetic hydrophilic polymer is a poly(olefinic alcohol).
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39. The method of claim 38, wherein the poly(olefinic alcohol) is polyvinyl alcohol or a copolymer thereof.
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40. The method of claim 27, wherein the synthetic hydrophilic polymer is a poly(N-vinyl lactam).
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41. The method of claim 40, wherein the poly(N-vinyl lactam) is selected from the group consisting of poly(vinyl pyrrolidone), poly(vinyl caprolactam), and copolymers thereof.
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42. The method of claim 21, wherein component A has the structural formula (I) and component B has the structural formula (II)
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43. The method of claim 42, wherein component C has the structural formula (III)
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44. The method of claim 43, wherein r and s are zero.
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45. The method of claim 43, wherein at least one of r and s is 1.
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46. The method of claim 1, wherein the nucleophilic groups of component A are selected from the group consisting of —
- NH2, —
NHR4, —
N(R4)2, —
SH, —
OH, —
COOH, —
C6H4—
OH, —
PH2, —
PHR5, —
P(R5)2, —
NH—
NH2, —
CO—
NH—
NH2, and —
C5H4N, wherein R4 and R5 are C1-C12 hydrocarbyl.
- NH2, —
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47. The method of claim 46, wherein the nucleophilic groups are selected from —
- NH2 and —
NHR4 where R4 is lower hydrocarbyl.
- NH2 and —
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48. The method of claim 47, wherein the electrophilic groups of component B are amino-reactive groups.
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49. The method of claim 48, wherein the amino-reactive groups contain an electrophilically reactive carbonyl group susceptible to nucleophilic attack by a primary or secondary amine.
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50. The method of claim 49, wherein the amino-reactive groups are carboxylic acid esters.
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51. The method of claim 49, wherein the amino-reactive groups are carboxylic acids or aldehydes.
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52. The method of claim 1, wherein the adhesive composition further comprises a biologically active agent.
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53. The method of claim 52, wherein the biologically active agent is a cell.
- placing into contact with the damaged tissue an adhesive composition comprised of
- 29. The method of 28, wherein the synthetic hydrophilic polymer is a polyalkylene oxide selected from the group consisting of polyethylene glycol and poly(ethylene oxide)-poly(propylene oxide) copolymers.
Specification