Biological Bioadhesive composition and methods of preparation and use

• US 6,921,532 B1
• Filed: 10/22/2002
• Issued: 07/26/2005
• Est. Priority Date: 06/22/2000
• Status: Expired due to Term

• Current Assignee: ITD34 Inc., Kevin Pauza
• Original Assignee: Spinal Restoration, Inc.
• Inventors: Davis, Thomas E., Austin, Sam L.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): George, Konata M.
• Application Number:
  US10/280,133
• Time in Patent Office: 1,008 Days
• Field of Search: 424/94.1, 424/94.64, 514/2, 514/169, 514/167, 514/168, 514170- 82
• US Class Current: 424/94.64
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/418 Agents promoting blood coagulation, blood-clotting agents, embolising agents
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/106 Fibrin; Fibrinogen
• CPC Class Codes: A61L 27/225 Fibrin; Fibrinogen
• CPC Class Codes: A61L 31/046 Fibrin; Fibrinogen

Abstract

The present invention relates generally to the preparation and use of biological tissue adhesives which rely on combining fibrinogen and thrombin. More particularly, the present invention relates to a method of preparing a fibrin sealant whereby said sealant is formed by reconstituting the fibrinogen or the thrombin component in the presence of biological and/or non-biological agents such as drugs, chemicals, and proteins. Preferably, these agents are introduced in solution, such as for example, a corticosteroid-containing solution like a betamethasone solution containing betamethasone acetate or betamethasone sodium phosphate; a triamicinolone solution; or a methylprednisolone solution. These solutions may be substituted for, or provided as a complement to, other solutions that are typically used in the preparation of fibrin sealants such as, for example, calcium chloride. The invention further relates to a novel method of using the improved fibrin sealant whereby the sealant and accompanying agent(s) are delivered directly to a critical site within the body and sealed in place due to the bio-static quality of the sealant. This provides therapeutic value to patients through prolonged presence, and optionally time-released delivery, of the specific agent(s) at the critical site.

Claims

1. A biological tissue adhesive for injection into a human body, the tissue adhesive comprising combined fibrinogen and thrombin, and a corticosteroid treatment agent.

2. A biological tissue adhesive as in claim 1, wherein a solution containing said corticosteroid treatment agent is added to said thrombin prior to combining the fibrinogen and the thrombin.

3. A biological tissue adhesive as in claim 2, wherein said solution is used to reconstitute the thrombin from a freeze-dried state.

4. A biological tissue adhesive as in claim 2, wherein said solution is added to thrombin prior to freezing said thrombin.

5. A biological tissue adhesive as in claim 2, wherein said solution is added to thrombin thawed from a frozen state.

6. A biological tissue adhesive as in claim 1, wherein a solution containing said corticosteroid treatment agent is added to the fibrinogen prior to combining the fibrinogen and the thrombin.

7. A biological tissue adhesive as in claim 6, wherein said solution is used to reconstitute the fibrinogen from a freeze-dried state.

8. A biological tissue adhesive as in claim 6, wherein said solution is added to the fibrinogen prior to freezing the fibrinogen.

9. A biological tissue adhesive as in claim 6, wherein said solution is added to fibrinogen thawed from a frozen state.

10. A biological tissue adhesive as in claim 1, wherein said solution further comprises calcium chloride.

11. A biological tissue adhesive as in claim 10, wherein the corticosteroid treatment agent comprises betamethasone.

12. A biological tissue adhesive as in claim 11, wherein the betamethasone comprises betamethasone sodium phosphate.

13. A biological tissue adhesive as in claim 11, wherein the betamethasone comprises betamethasone acetate.

14. A biological tissue adhesive an in claim 10, wherein the corticosteroid treatment agent comprises triamicinolone.

15. A biological tissue adhesive as in claim 10, wherein the corticosteroid treatment agent comprises methylprednisolone.

16. A biological tissue adhesive for injection into a human body, the tissue adhesive comprising combined fibrinogen and thrombin, wherein at least one of the fibrinogen and thrombin is mixed, prior to combination of the fibrinogen and thrombin, with a solution comprising corticosteroid treatment agent and calcium chloride.

17. A biological tissue adhesive as in claim 16, wherein said solution is mixed with said thrombin prior to combining the fibrinogen and the thrombin.

18. A biological tissue adhesive as in claim 17, wherein said solution is used to reconstitute the thrombin from a freeze-dried state.

19. A biological tissue adhesive as in claim 17, wherein said solution is mixed with the thrombin prior to freezing the thrombin.

20. A biological tissue adhesive as in claim 16, wherein a solution is added to the fibrinogen prior to combining the fibrinogen and the thrombin.

21. A biological tissue adhesive as in claim 20, wherein said solution is used to reconstitute the fibrinogen from a freeze-dried state.

22. A biological tissue adhesive as in claim 20, wherein said solution is mixed with the fibrinogen prior to freezing the fibrinogen.

33. An adhesive as in claim 20, wherein said solution is added to fibrinogen thawed from a frozen state.

23. A biological tissue adhesive comprising combined fibrinogen and thrombin and a corticosteroid treatment agent injected into biological tissue.

24. An adhesive as in claim 23, wherein said combined fibrinogen and thrombin and said corticosteroid treatment agent are injected into human biological tissue.

25. An adhesive as in claim 24, wherein said combined fibrinogen and thrombin and said corticosteroid are injected into a human spine nucleas pulposus.

26. An adhesive as in claim 23, wherein a solution containing said corticosteroid treatment agent is added to said thrombin prior to combining the fibrinogen and the thrombin.

27. An adhesive as in claim 26, wherein said solution is used to reconstitute the thrombin from a freeze-dried state.

28. An adhesive as in claim 26, wherein said solution is added to thrombin prior to freezing said thrombin.

29. An adhesive as in claim 26, wherein said solution is added to thrombin thawed from a frozen state.

30. An adhesive as in claim 23, wherein a solution containing said corticosteroid treatment agent is added to the fibrinogen prior to combining the fibrinogen and the thrombin.

31. An adhesive as in claim 30, wherein said solution is used to reconstitute the fibrinogen from a freeze-dried state.

32. An adhesive as in claim 30, wherein said solution is added to the fibrinogen prior to freezing the fibrinogem.

34. An adhesive as in claim 23, wherein said solution further comprises calcium chloride.

35. An adhesive as in claim 34, wherein the cortisteroid treatment agent comprises betamethasone.

36. An adhesive as in claim 35, wherein the betamethasone comprises betamethasone sodium phosphate.

37. An adhesive as in claim 35, wherein the betamethasone comprises betamethasone acetate.

38. An adhesive as in claim 34, wherein the corticosteroid treatment agent comprises triamicinolone.

39. An adhesive as in claim 34, wherein the corticosteroid treatment agent comprises methylprednisolone.

40. A biological tissue adhesive comprising fibrinogen and thrombin combined during injection into biological tissue, wherein at least one of the fibrinogen and thrombin is mixed, prior to combination of the fibrinogen and thrombin, with a solution comprising corticosteroid treatment agent and calcium chloride.

41. An adhesive as in claim 40, wherein said fibrinogen and thrombin are combined during injection into human biological tissue.

42. Ah adhesive as in claim 41, wherein said fibrinogen and thrombin are combined during injection into a human spine nucleus pulposus.

43. A biological tissue adhesive as in claim 40, wherein said solution is mixed with said thrombin prior to combining the fibrinogen and thrombin.

44. A biological tissue adhesive as in claim 43, wherein said solution is used to reconstitute the thrombin from a freeze-dried state.

45. A biological tissue adhesive as in claim 43, wherein said solution ia mixed with the thrombin prior to freezing the thrombin.

46. A biological tissue adhesive as in claim 40, wherein said solution is mixed with the thrombin prior to freezing the thrombin.

47. A biological tissue adhesive as in claim 46, wherein said solution is used to reconstitute the fibrinogen from a freeze-dried state.

48. A biological tissue adhesive as in claim 46, wherein said solution is mixed with the fibrinogen prior to freezing the fibrinogen.