FUNCTIONALIZED SURGICAL ADHESIVES

• US 20100215659A1
• Filed: 02/19/2010
• Published: 08/26/2010
• Est. Priority Date: 02/21/2009
• Status: Active Grant

• Current Assignee: Sofradim Production
• Original Assignee: Sofradim Production
• Inventors: Ladet, Sebastien
• Granted Patent: US 8,968,733 B2
• Time in Patent Office: Days
• US Class Current: 424/135.100
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61L 24/04 containing macromolecular materials
• CPC Class Codes: A61L 24/10 Polypeptides; Proteins A61L24/043 takes precedence
• CPC Class Codes: A61L 24/108 Specific proteins or polypeptides not covered by groups A61L24/102 - A61L24/106
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like

Abstract

A bioadherent composition includes a first mixture containing a plurality of reactive members of a specific binding pair, said reactive members being bound to a ligand capable of binding a receptor on biological tissue, and a second mixture containing a plurality of complementary reactive members of the specific binding pair, said complementary reactive members being bound to a ligand capable of binding a receptor on biological tissue, said reactive members capable of forming covalent bonds with said complementary reactive members via a reaction selected from Huisgen cycloaddition reactions, Diels-Alder reactions, and/or thiol-alkene reactions. A method for bonding biological tissue involves utilizing the bioadherent composition.

Claims

1. A method for bonding biological tissue comprising:

providing a first mixture containing a plurality of reactive members of a specific binding pair;

providing a second mixture containing a plurality of complementary reactive members of the specific binding pair;

applying the first mixture to a first biological tissue surface to affix the reactive members to the first biological tissue surface;

applying the second mixture to a second biological tissue surface to affix the complementary reactive members to the second biological tissue surface;

wherein upon contact of the reactive members on the first biological tissue surface with the complimentary reactive members on the second biological tissue surface, covalent bonds are formed between the reactive members and the complementary reactive members, thus adhering the first biological tissue surface to the second biological tissue surface.

2. The method for bonding biological tissue according to claim 1 wherein the members of the specific binding pair bind to one another via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiolene reaction.

3. The method for bonding biological tissue according to claim 2 wherein the members of the specific binding pair are alkynes and azides.

4. The method for bonding biological tissue according to claim 3 wherein the reactive member is an alkyne and the complementary reactive member is an azide.

5. The method for bonding biological tissue according to claim 3 wherein the reactive members is an azide and the complementary reactive member is an alkyne.

6. The method for bonding biological tissue according to claim 2 wherein the reaction is catalyzed by copper to activate an alkyne and an azide for [3+2] cycloaddition.

7. The method for bonding biological tissue according to claim 2 wherein the reaction involves a cyclooctyne reagent and an azide for [3+2] cycloaddition.

8. The method for bonding biological tissue according to claim 2 wherein the members of the specific binding pair are thiols and alkenes.

9. The method for bonding biological tissue according to claim 2 wherein the members of the specific binding pair are dienes and alkenes.

10. The method for bonding biological tissue according to claim 1 wherein the tissue is provided with complementary reactive members of the specific binding pair by applying a mixture or an aerosol containing the complementary reactive members to the tissue, the complementary reactive members being conjugated to a linker adapted to link the complementary reactive members to the tissue.

11. The method for bonding biological tissue according to claim 10 wherein the complementary reactive members are attached to the tissue via an RGD linker.

12. The method for bonding biological tissue according to claim 10 wherein the complementary reactive members are attached to the tissue via a ligand-receptor linkage.

13. The method for bonding biological tissue according to claim 12 wherein the complementary reactive members are conjugated to a linker selected from the group consisting of antibody, Fab, F(ab′

)₂, Fv, single chain antibody (SCA) and single complementary-determining region (CDR).

14. The method for bonding biological tissue according to claim 10 wherein the linker is degraded by hydrolysis or enzymatic action.

15. The method for bonding biological tissue according to claim 10 wherein the ligand binds to a receptor selected from the group consisting of peptides, oligosaccharides, oligonucleotides and lipids.

16. A bioadherent composition which comprises:

a first mixture containing a plurality of reactive members of a specific binding pair, said reactive members being bound to a ligand capable of binding a receptor on biological tissue; and

a second mixture containing a plurality of complementary reactive members of the specific binding pair, said complementary reactive members being bound to a ligand capable of binding a receptor on biological tissue, said reactive members capable of forming covalent bonds with said complementary reactive members via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction.

17. The bioadherent composition according to claim 16 wherein the members of the specific binding pair bind to one another via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction.

18. The bioadherent composition according to claim 17 wherein the members of the specific binding pair are alkynes and azides.

19. The bioadherent composition according to claim 18 wherein the reactive member is an alkyne and the complementary reactive member is an azide.

20. The bioadherent composition according to claim 18 wherein the reactive members is an azide and the complementary reactive member is an alkyne.

21. The bioadherent composition according to claim 17 wherein the reaction is catalyzed by copper to activate an alkyne and an azide for [3+2] cycloaddition.

22. The bioadherent composition according to claim 17 wherein the reaction involves a cyclooctyne reagent and an azide for [3+2] cycloaddition.

23. The bioadherent composition according to claim 17 wherein the members of the specific binding pair are thiols and alkenes.

24. The bioadherent composition according to claim 17 wherein the members of the specific binding pair are dienes and alkenes.

25. The bioadherent composition according to claim 16 wherein the tissue is provided with complementary reactive members of the specific binding pair by applying a mixture or an aerosol containing the complementary reactive members to the tissue, the complementary reactive members being conjugated to a linker adapted to link the complementary reactive members to the tissue.

26. The bioadherent composition according to claim 25 wherein the complementary reactive members are attached to the tissue via an RGD linker.

27. The bioadherent composition according to claim 25 wherein the complementary reactive members are attached to the tissue via a ligand-receptor linkage.

28. The bioadherent composition according to claim 27 wherein the complementary reactive members are conjugated to a linker selected from the group consisting of antibody, Fab, F(ab′

)₂, Fv, single chain antibody (SCA) and single complementary-determining region (CDR).

29. The bioadherent composition according to claim 25 wherein the linker is degraded by hydrolysis or enzymatic action.

30. The bioadherent composition according to claim 25 wherein the ligand binds to a receptor selected from the group consisting of peptides, oligosaccharides, oligonucleotides and lipids.

31. A kit which comprises:

a first container containing a first mixture which is a solution or suspension containing a plurality of reactive members of a specific binding pair, said reactive members being bound to a ligand capable of binding a receptor on biological tissue;

a second container containing a second mixture which is a solution or suspension containing a plurality of complementary reactive members of the specific binding pair, said complementary reactive members being bound to a ligand capable of binding a receptor on biological tissue, said reactive members capable of forming covalent bonds with said complementary reactive members via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction; and

at least one dispenser for delivering the first mixture or the second mixture to the surface of biological tissue.

32. The kit according to claim 31 wherein the members of the specific binding pair bind to one another via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction.

33. The kit according to claim 32 wherein the members of the specific binding pair are alkynes and azides.

34. The kit according to claim 32 wherein the members of the specific binding pair are thiols and alkenes.

35. The kit according to claim 32 wherein the members of the specific binding pair are dienes and alkenes.

36. The kit according to claim 32 wherein the reaction is catalyzed by copper to activate an alkyne and an azide for [3+2] cycloaddition.

37. The kit according to claim 32 wherein the reaction involves a cyclooctyne reagent and an azide for [3+2] cycloaddition.

38. The kit according to claim 31 wherein an applicator is provided for applying a mixture or an aerosol containing the complementary reactive members to the tissue, the complementary reactive members being conjugated to a linker adapted to link the complementary reactive members to the tissue.

39. The kit according to claim 38 wherein the complementary reactive members are attached to an RGD linker.

40. The kit according to claim 38 wherein the complementary reactive members are attached to a ligand-containing linkage.

41. The kit according to claim 40 wherein the complementary reactive members are conjugated to a linker selected from the group consisting of antibody, Fab, F(ab′

)₂, Fv, single chain antibody (SCA) and single complementary-determining region (CDR).

42. The kit according to claim 38 wherein the linker is adapted to be degraded by hydrolysis or enzymatic action.

43. The kit according to claim 38 wherein the ligand is adapted to bind to a receptor selected from the group consisting of peptides, oligosaccharides, oligonucleotides and lipids.

44. The kit according to claim 31 further comprising a container containing a solution of a metal.

45. The kit according to claim 31 further comprising a generator for producing ultraviolet radiation or microwaves.