Methods for tissue repair using adhesive materials
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C08F-283/00
C08F-283/04
C08G-063/91
C08G-069/48
C08L-089/00
출원번호
US-0262640
(2002-09-30)
발명자
/ 주소
Sehl, Louis C.
Trollsas, Olof Mikael
Wallace, Donald G.
Toman, David
DeLustro, Frank A.
Schroeder, Jacqueline A.
Chu, George H.
출원인 / 주소
Cohesion Technologies, Inc.
대리인 / 주소
Reed Dianne E.
인용정보
피인용 횟수 :
179인용 특허 :
131
초록▼
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 betwe
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.
대표청구항▼
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 compone
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. 2. The method of claim 1, wherein the damaged tissue is herniated tissue and the method further comprises placing a surgically acceptable patch in contact with the herniated tissue. 3. The method of claim 1, wherein the adhesive is placed into contact with the damaged tissue via laparoscopic techniques. 4. The method of claim 2, wherein the surgically acceptable patch is a mesh plug or mesh sheet. 5. The method of claim 2, wherein the herniated tissue is a result of a condition selected from the group consisting inguinal hernia, femoral hernia, scrotal hernia, ventral hernia, umbilical hernia, ventral/epigastric hernia, incisional hernia, spigelian hernia, recurrent hernia, recurrent incisional hernia, bilateral hernia, stoma hernia, and hiatus hernia. 6. The method of claim 1, wherein the hydrophilic polymer is synthetic. 7. The method of claim 1, wherein the hydrophilic polymer is naturally occurring. 8. The method of claim 7, wherein the naturally occurring hydrophilic polymer is selected from the group consisting of proteins, carboxylated polysaccharides, aminated polysaccharides, glycosaminoglycans, and activated polysaccharides. 9. The method of claim 8, wherein the naturally occurring polymer is a protein. 10. The method of claim 8, wherein the naturally occurring polymer is collagen. 11. The method of claim 10, wherein the collagen is nonfibrillar collagen. 12. The method of claim 11, wherein the nonfibrillar collagen is a chemically modified collagen. 13. The method of claim 12, wherein the chemically modified collagen is methylated collagen. 14. The method of claim 11, wherein the nonfibrillar collagen is selected from the group consisting of: type IV collagen, type VI collagen, and type VII collagen. 15. The method of claim 10, wherein the collagen is fibrillar collagen. 16. The method of claim 10, wherein the collagen comprises a mixture of nonfibrillar collagen and fibrillar collagen. 17. The method of claim 15, wherein the collagen comprises a mixture of particulate crosslinked fibrillar collagen and noncrosslinked fibrillar collagen. 18. The method of claim 17, wherein the particulate crosslinked fibrillar collagen comprises glutaraldehyde-crosslinked collagen. 19. The method of claim 17, wherein the particulate crosslinked fibrillar collagen comprises between about 25% to about 95% and the noncrosslinked fibrillar collagen comprises between about 5% to about 75% by weight of the composition. 20. The method of claim 6, wherein the collagen is denatured collagen. 21. The method of claim 1, wherein the adhesive composition further comprises a third crosslinkable component C that is biocompatible and nonimmunogenic and has at least one functional group selected from(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. 22. The method of claim 1, wherein component A has the structural formula (I) and component B has the structural formula (II) 1 (−[Q 1 ] q −X) m (I) 2 (−[Q 2 ] r −Y) n (II)wherein:R 1 and R 2 are independently selected from the group cons isting of C 2 to C 14 hydrocarbyl, heteroatom-containing C 2 to C 14 hydrocarbyl, hydrophilic polymers, and hydrophobic polymers;X represents one of the m nucleophilic groups of component A;Y represents one of the n electrophilic groups of component B;Q 1 and Q 2 are linking groups; andq and r are independently zero or 1. 23. The method of claim 21, wherein component C has the structural formula (III) 3 (−[Q 3 ] s −Fn) p (III)wherein:R 3 is selected from the group consisting of C 2 to C 14 hydrocarbyl, heteroatom-containing C 2 to C 14 hydrocarbyl, hydrophilic polymers, and hydrophobic polymers;Fn represents a functional group on component C; ands is zero or 1. 24. The method of claim 22, wherein at least one of R 1 and R 2 is a synthetic hydrophilic polymer. 25. The method of claim 24, wherein:(a) R 1 is a first synthetic hydrophilic polymer; and(b) R 2 is selected from the group consisting of (i) a second synthetic hydrophilic polymer that may or may not be the same as R 1 and (ii) C 2 to C 14 hydrocarbyl groups containing zero to 2 heteroatoms selected from N, O and S. 26. The method of claim 25, wherein the synthetic hydrophilic polymer is of a linear, branched, dendrimeric, hyperbranched, or star polymer. 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. 28. The method of claim 27, wherein the synthetic hydrophilic polymer is a polyalkylene oxide or polyglycerol. 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. 30. The method of claim 29, wherein the polyalkylene oxide is polyethylene glycol. 31. The method of claim 27, wherein the synthetic hydrophilic polymer is a poly(oxyalkylene)-substituted diol or polyol. 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. 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. 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. 35. The method of claim 27, wherein the synthetic hydrophilic polymer is polymaleic acid. 36. The method of claim 27, wherein the synthetic hydrophilic polymer is a polyacrylamide. 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. 38. The method of claim 27, wherein the synthetic hydrophilic polymer is a poly(olefinic alcohol). 39. The method of claim 38, wherein the poly(olefinic alcohol) is polyvinyl alcohol or a copolymer thereof. 40. The method of claim 27, wherein the synthetic hydrophilic polymer is a poly(N-vinyl lactam). 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 . 42. The method of claim 21, wherein component A has the structural formula (I) and component B has the structural formula (II) 1 (−[Q 1 ] q −X) m (I) 2 (−[Q 2 ] r −Y) n (II)wherein:R 1 and R 2 are independently selected from the group consisting of C 2 to C 14 hydrocarbyl, heteroatom-containing C 2 to C 14 hydrocarbyl, hydrophilic polymers, and hydrophobic polymers;X represents one of the m nucleophilic groups of component A;Y represents one of the n electrophilic groups of component B;Q 1 and Q 2 are linking groups; andq and r are independently zero or 1. 43. The method of claim 42, wherein component C has the structural formula (III) 3 (−[Q 3 ] s −FN) p (III)wherein:R 3 is selected from the group consisting of C 2 to C 14 hydrocarbyl, heteroatom-containing C 2 to C 14 hydrocarbyl, hydrophilic polymers, and hydrophobic polymers;Fn represents a functional group on component C; ands is zero or 1. 44. The method of claim 43, wherein r and s are zero. 45. The method of claim 43, wherein at least one of r and s is 1. 46. The method of claim 1, wherein the nucleophilic groups of component A are selected from the group consisting of —NH 2 , —NHR 4 , —N(R 4 ) 2 , —SH, —OH, —COOH, —C 6 H 4 —OH, —PH 2 , —PHR 5 , —P(R 5 ) 2 , —NH—NH 2 , —CO—NH—NH 2 , and —C 5 H 4 N, wherein R 4 and R 5 are C 1-C 12 hydrocarbyl. 47. The method of claim 46, wherein the nucleophilic groups are selected from —NH 2 and —NHR 4 where R 4 is lower hydrocarbyl. 48. The method of claim 47, wherein the electrophilic groups of component B are amino-reactive groups. 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. 50. The method of claim 49, wherein the amino-reactive groups are carboxylic acid esters. 51. The method of claim 49, wherein the amino-reactive groups are carboxylic acids or aldehydes. 52. The method of claim 1, wherein the adhesive composition further comprises a biologically active agent. 53. The method of claim 52, wherein the biologically active agent is a cell.
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