Claims
- 1. A method for augmenting soft or hard tissue within a mammalian body, comprising:
(a) providing a first crosslinkable component having m nucleophilic groups, wherein m≧2; (b) providing a second crosslinkable component having n electrophilic groups capable of reaction with the m nucleophilic groups to form covalent bonds, wherein n≧2 and m+n≧5; (c) applying the first and second crosslinkable components to the tissue; and (d) allowing the first and second crosslinkable components to crosslink in situ, wherein the first and second crosslinkable components are biocompatible, synthetic, and nonimmunogenic.
- 2. The method of claim 1, wherein step (c) comprises simultaneously applying the first and second crosslinkable components to the tissue.
- 3. The method of claim 2, wherein prior to step (c), the first and second crosslinkable components are admixed to provide a reaction mixture and initiate crosslinking, and step (c) comprises applying the reaction mixture to the tissue.
- 4. The method of claim 1, wherein the m nucleophilic groups in the first crosslinkable component are identical.
- 5. The method of claim 1, wherein at least two of the m nucleophilic groups in the first crosslinkable component are different.
- 6. The method of claim 1, wherein the n electrophilic groups in the second crosslinkable component are identical.
- 7. The method of claim 4, wherein the n electrophilic groups in the second crosslinkable component are identical.
- 8. The method of claim 5, wherein the n electrophilic groups in the second crosslinkable component are identical.
- 9. The method of claim 1, wherein the n electrophilic groups in the second crosslinkable component are different.
- 10. The method of claim 4, wherein at least two of the n electrophilic groups in the second crosslinkable component are different.
- 11. The method of claim 5, wherein at least two of the n electrophilic groups in the second crosslinkable component are different.
- 12. The method of claim 1, wherein the m nucleophilic groups are bound to the first crosslinkable component through linking groups.
- 13. The method of claim 1, wherein the n nucleophilic groups are bound to the second crosslinkable component through linking groups.
- 14. The method of claim 1, wherein at least one of the first and second crosslinkable components is comprised of a hydrophilic polymer.
- 15. The method of claim 1, wherein at least one of the first and second crosslinkable components is comprised of a hydrophobic polymer.
- 16. The method of claim 1, wherein the m nucleophilic groups are primary amino groups.
- 17. The method of claim 16, wherein the first crosslinkable component is C2-C6 hydrocarbyl susbstituted with amino groups.
- 18. The method of claim 16, wherein the first crosslinkable component is a secondary or tertiary amine NR1R2R3 wherein R1 is hydrogen or an amino-substituted lower alkyl group, and R2 and R3 are amino-substituted lower alkyl groups.
- 19. The method of claim 16, wherein the n electrophilic groups are selected from the group consisting of succinimidyl ester, sulfosuccinimidyl ester, maleimido, epoxy, isocyanato, thioisocyanato, and ethenesulfonyl.
- 20. The method of claim 19, wherein the n electrophilic groups are selected from the group consisting of succinimidyl ester and sulfosuccinimidyl ester.
- 21. The method of claim 1, wherein the m nucleophilic groups are sulfhydryl groups.
- 22. The method of claim 21, wherein the n electrophilic groups are sulfhydryl-reactive groups selected so as to form a thioester, thioether, or disulfide linkage upon reaction with the sulfhydryl groups.
- 23. The method of claim 1, wherein n=2.
- 24. The method of claim 1, wherein m=2.
- 25. The method of claim 1, wherein the crosslinking conditions comprise admixture in an aqueous medium.
- 26. The method of claim 25, wherein the first and second crosslinkable components each represent about 0.5 wt. % to about 20 wt. % of the composition formed upon admixture.
- 27. The method of claim 25, wherein the crosslinking conditions further comprise admixture at a pH in the range of 7 to 8.
- 28. The method of claim 27, wherein the first and second crosslinkable components are at concentrations of 20 mg/mL to 200 mg/mL of the composition formed upon admixture.
- 29. The method of claim 1, wherein the first crosslinkable component is in an aqueous solution, the second crosslinkable component is in dry, particulate form, and admixing comprises combining the second crosslinkable component with the aqueous solution of the first crosslinkable component.
- 30. The method of claim 29, wherein the first and second crosslinkable components each represent about 0.5 wt. % to about 20 wt. % of the composition formed upon admixture.
- 31. The method of claim 29, wherein the crosslinking conditions further comprise admixture at a pH in the range of 7 to 8.
- 32. The method of claim 31, wherein the first and second crosslinkable components are at concentrations of 20 mg/mL to 200 mg/mL of the composition formed upon admixture.
- 33. The method of claim 1, wherein the first crosslinkable component is present in a molar excess relative to the second crosslinkable component.
- 34. The method of claim 1, wherein the second crosslinkable component is present in a molar excess relative to the first crosslinkable component.
- 35. A method for preventing the formation of adhesions following surgery or injury, comprising:
(a) providing a first crosslinkable component having m nucleophilic groups, wherein m≧2; (b) providing a second crosslinkable component having n electrophilic groups capable of reaction with the m nucleophilic groups to form covalent bonds, wherein n≧2 and m+n≧5; (c) applying the first and second crosslinkable components to the tissues comprising, surrounding, and/or adjacent to a wound resulting from surgery or injury; and (d) allowing the first and second crosslinkable components to crosslink in situ, wherein the first and second crosslinkable components are biocompatible, synthetic, and nonimmunogenic.
- 36. The method of claim 35, wherein step (c) comprises simultaneously applying the first and second crosslinkable components to the tissues.
- 37. The method of claim 36, wherein prior to step (c), the first and second crosslinkable components are admixed to provide a reaction mixture and initiate crosslinking, and step (c) comprises applying the reaction mixture to the tissues.
- 38. The method of claim 35, wherein the m nucleophilic groups in the first crosslinkable component are identical.
- 39. The method of claim 35, wherein at least two of the m nucleophilic groups in the first crosslinkable component are different.
- 40. The method of claim 35, wherein the n electrophilic groups in the second crosslinkable component are identical.
- 41. The method of claim 36, wherein the n electrophilic groups in the second crosslinkable component are identical.
- 42. The method of claim 37, wherein the n electrophilic groups in the second crosslinkable component are identical.
- 43. The method of claim 35, wherein the n electrophilic groups in the second crosslinkable component are different.
- 44. The method of claim 36, wherein at least two of the n electrophilic groups in the second crosslinkable component are different.
- 45. The method of claim 37, wherein at least two of the n electrophilic groups in the second crosslinkable component are different.
- 46. The method of claim 35, wherein the m nucleophilic groups are bound to the first crosslinkable component through linking groups.
- 47. The method of claim 35, wherein the n nucleophilic groups are bound to the second crosslinkable component through linking groups.
- 48. The method of claim 35, wherein at least one of the first and second crosslinkable components is comprised of a hydrophilic polymer.
- 49. The method of claim 35, wherein at least one of the first and second crosslinkable components is comprised of a hydrophobic polymer.
- 50. The method of claim 35, wherein the m nucleophilic groups are primary amino groups.
- 51. The method of claim 50, wherein the first crosslinkable component is C2-C6 hydrocarbyl susbstituted with amino groups.
- 52. The method of claim 50, wherein the first crosslinkable component is a secondary or tertiary amine NR1R2R3 wherein R1 is hydrogen or an amino-substituted lower alkyl group, and R2 and R3 are amino-substituted lower alkyl groups.
- 53. The method of claim 50, wherein the n electrophilic groups are selected from the group consisting of succinimidyl ester, sulfosuccinimidyl ester, maleimido, epoxy, isocyanato, thioisocyanato, and ethenesulfonyl.
- 54. The method of claim 53, wherein the n electrophilic groups are selected from the group consisting of succinimidyl ester and sulfosuccinimidyl ester.
- 55. The method of claim 35, wherein the m nucleophilic groups are sulfhydryl groups.
- 56. The method of claim 55, wherein the n electrophilic groups are sulfhydryl-reactive groups selected so as to form a thioester, thioether, or disulfide linkage upon reaction with the sulfhydryl groups.
- 57. The method of claim 35, wherein n=2.
- 58. The method of claim 35, wherein m=2.
- 59. The method of claim 35, wherein the crosslinking conditions comprise admixture in an aqueous medium.
- 60. The method of claim 59, wherein the first and second crosslinkable components each represent about 0.5 wt. % to about 20 wt. % of the composition formed upon admixture.
- 61. The method of claim 59, wherein the crosslinking conditions further comprise admixture at a pH in the range of 7 to 8.
- 62. The method of claim 61, wherein the first and second crosslinkable components are at concentrations of 20 mg/mL to 200 mg/mL of the composition formed upon admixture.
- 63. The method of claim 35, wherein the first crosslinkable component is in an aqueous solution, the second crosslinkable component is in dry, particulate form, and admixing comprises combining the second crosslinkable component with the aqueous solution of the first crosslinkable component.
- 64. The method of claim 63, wherein the first and second crosslinkable components each represent about 0.5 wt % to about 20 wt. % of the composition formed upon admixture.
- 65. The method of claim 63, wherein the crosslinking conditions further comprise admixture at a pH in the range of 7 to 8.
- 66. The method of claim 65, wherein the first and second crosslinkable components are at concentrations of 20 mg/mL to 200 mg/mL of the composition formed upon admixture.
- 67. The method of claim 35, wherein the first crosslinkable component is present in a molar excess relative to the second crosslinkable component.
- 68. The method of claim 35, wherein the second crosslinkable component is present in a molar excess relative to the first crosslinkable component.
CROSS REFERENCES
[0001] This application is a continuation of U.S. application Ser. No. 10/364,762, filed Feb. 10, 2003, which is a continuation of U.S. application Ser. No. 09/932,536, filed Aug. 17, 2001, and issued as U.S. Pat. No. 6,534,591 on Mar. 18, 2003, which was a continuation of U.S. application Ser. No. 09/733,739, filed Dec. 8, 2000, which is a continuation of U.S. application Ser. No. 09/302,852, filed Apr. 30, 1999, and issued as U.S. Pat. No. 6,166,130 on Dec. 26, 2000, which was a continuation of U.S. application Ser. No. 09/229,851, filed Jan. 13, 1999, and issued as U.S. Pat. No. 6,051,648 on Apr. 18, 2000, which was a continuation of U.S. application Ser. No. 08/769,806, filed Dec. 18, 1996, and issued as U.S. Pat. No. 5,874,500 on Feb. 23, 1999, which was a continuation-in-part of U.S. application Ser. No. 08/573,799, filed Dec. 18, 1995, now abandoned, all of which are incorporated by reference in their entireties under 35 U.S.C. § 120.
Continuations (6)
|
Number |
Date |
Country |
Parent |
10364762 |
Feb 2003 |
US |
Child |
10766104 |
Jan 2004 |
US |
Parent |
09932536 |
Aug 2001 |
US |
Child |
10364762 |
Feb 2003 |
US |
Parent |
09733739 |
Dec 2000 |
US |
Child |
09932536 |
Aug 2001 |
US |
Parent |
09302852 |
Apr 1999 |
US |
Child |
09733739 |
Dec 2000 |
US |
Parent |
09229851 |
Jan 1999 |
US |
Child |
09302852 |
Apr 1999 |
US |
Parent |
08769806 |
Dec 1996 |
US |
Child |
09229851 |
Jan 1999 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
08573799 |
Dec 1995 |
US |
Child |
08769806 |
Dec 1996 |
US |