Claims for Patent: 6,548,729

Summary for Patent: 6,548,729

Title:	Fibrin sponge
Abstract:	The invention relates to a fibrin sponge comprising a residual moisture content of at least 3%, preferably of 3 to 35%, in particular 10 to 20%, and preferably containing a blood clotting activator or proactivator, a method of preparing this fibrin sponge as well as a kit for wound gluing which comprises the fibrin sponge and a component containing a blood clotting factor. The sponge according to the present invention is suitable for hemostasis, tissue adhesion and aiding wound healing.
Inventor(s):	Seelich; Thomas (Vienna, AT), Scheel; Edgar (Hagen, DE), Odar; Johann (Muhlhausen, DE), Delmotte; Yves Alain (Tertre, BE)
Assignee:	Baxter Aktiengesellschaft (Vienna, AT) Baxter International Inc. (Deerfield, IL)
Application Number:	09/451,361
Patent Claims:	1. A storage-stable fibrin sponge comprising a residual moisture of at least 10%. 2. The storage-stable fibrin sponge as set forth in claim 1, wherein said residual moisture ranges from 10% to 35%. 3. The storage-stable fibrin sponge as set forth in claim 1, wherein said residual moisture ranges from 10 to 20%. 4. The storage-stable fibrin sponge as set forth in claim 1, further comprising a blood clotting activator or proactivator. 5. The storage-stable fibrin sponge as set forth in claim 4, wherein said blood clotting activator or proactivator is selected from the group consisting of thrombin, prothrombin, activated factor X, activated prothrombin complex, FEIBA, calcium ions and mixtures thereof. 6. The storage-stable fibrin sponge as set forth in claim 5, wherein said blood clotting activator is thrombin, said thrombin being comprised in an amount of from 1 to 300 U/cm.sup.3. 7. The storage-stable fibrin sponge as set forth in claim 5, wherein said thrombin is comprised in an amount of from 5 to 100 U/cm.sup.3. 8. The storage-stable fibrin sponge as set forth in claim 5, wherein said thrombin is comprised in an amount of from 10 to 50 U/cm3. 9. The storage-stable fibrin sponge as set forth in claim 1, further comprising a member selected from the group consisting of: stabilizers, preservatives, antibiotics, therapeutic agents, antifibrinolytic agents, growth factors, further plasma proteins, enzymes, inhibitors and mixtures of these agents. 10. The storage-stable fibrin sponge as set forth in claim 1, said fibrin sponge having a liquid absorption capacity of at least the 2-fold of its own weight. 11. The storage-stable fibrin sponge as set forth in claim 1, wherein said fibrin sponge has a liquid absorption capacity which is 4-fold of its own weight. 12. The storage-stable fibrin sponge as set forth in claim 1, wherein said fibrin sponge is virus inactivated. 13. The storage-stable fibrin sponge as set forth in claim 12, wherein said virus inactivation has been effected in two independent virus inactivation steps. 14. The storage-stable fibrin sponge as set forth in claim 1, said fibrin sponge being free from elutable plasma proteins. 15. The storage-stable fibrin sponge as set forth in claim 1, said fibrin sponge being free from elutable thrombin. 16. The storage-stable fibrin sponge as set forth in claim 1, said fibrin sponge having been prepared from virus-safe starting substances. 17. The storage-stable fibrin sponge as set forth in claim 1, said fibrin sponge being provided in an aseptic package and in ready-to-use form. 18. The storage-stable fibrin sponge as set forth in claim 1, said fibrin sponge having a thickness of at least 1 mm. 19. The storage-stable fibrin sponge as set forth in claim 1, said fibrin sponge having a thickness of between 5 and 10 mm. 20. The storage-stable fibrin sponge as set forth in claim 1, said fibrin sponge being multilayered. 21. The storage-stable fibrin sponge as set forth in claim 20, wherein at least one layer of said multilayered fibrin sponge has hemostatic properties. 22. The storage-stable fibrin sponge as set forth in claim 1, said fibrin sponge having a specific weight of between 0.005 and 0.15 g/cm3. 23. The storage-stable fibrin sponge as set forth in claim 22, wherein said specific weight of said fibrin sponge ranges between 0.01 and 0.09 g/cm3. 24. The storage-stable fibrin sponge as set forth in claim 22, wherein said specific weight of said fibrin sponge ranges between 0.02 and 0.05 g/cm3. 25. A kit for wound coverage, said kit comprising a storage-stable fibrin sponge having a residual moisture of at least 10% and a component containing a blood clotting factor. 26. The kit as set forth in claim 25, wherein said blood clotting factor is selected from the group consisting of fibrinogen, factor XIII, fibronectin, thrombin and mixtures of said factors. 27. A method of preparing a fibrin sponge, said method comprising preparing a fibrin clot by mixing a fibrinogen solution with a thrombin solution and incubating the resulting mixed solution at a certain temperature for a period of time sufficient for formation of said fibrin clot, b) deep-freezing and lyophilizing said fibrin clot, and c) adjusting a residual moisture in said fibrin clot to at least 10%. 28. A method as set forth in claim 27, wherein said fibrinogen solution contains factor XIII, and said thrombin solution contains Ca.sup.2 + ions, and said temperature for incubating ranges between 20 and 37.degree. C., and incubating of said mixed solution is carried out for a period of time sufficient for cross-linking of said fibrin formed, and wherein a residual moisture of from 10% to 35% is adjusted. 29. The method as set forth in claim 27, wherein said incubating of said mixed solution is carried out for a period of time of from 10 min to 24 h, and wherein a residual moisture of from 10 to 20% is adjusted. 30. The method as set forth in claim 27, further comprising packing said fibrin sponge in a suitable container. 31. The method as set forth in claim 30, wherein said container is at least one of air-tight and water-tight. 32. The method as set forth in claim 27, wherein at least one of said fibrinogen solution and said thrombin solution further comprises at least one of another plasma protein, another active substance and an auxiliary agent. 33. The method as set forth in claim 32, further comprising at least one of washing said fibrin clot with water or with an aqueous solution and incubating said fibrin clot with an additional solution, said additional solution containing at least one member selected from the group consisting of thrombin, another plasma protein and another active substance. 34. The method as set forth in claim 33, wherein said at least one of washing and incubating with said further solution containing said at least one of thrombin, an additional plasma protein and an auxiliary agent is effected after lyophilizing, followed by another deep-freezing and lyophilizing step. 35. The method as set forth in claim 32, wherein said additional plasma protein is selected from the group consisting of fibronectin, a fibrinolysis inhibitor, plasminogen and albumin, and wherein said additional active substance is selected from the group consisting of a non-plasmatic and synthetic fibrinolysis inhibitor, an antibiotic and a growth hormone. 36. The method as set forth in claim 32, wherein said auxiliary agent is selected from the group consisting of sugar, sugar alcohol, polyol, amino acid, tenside, plasticizer and a moistening agent. 37. The method as set forth in claim 32, wherein said auxiliary agent is glycerol. 38. The method as set forth in claim 27, further comprising foaming said fibrinogen solution or a mixture of said fibrinogen solution with said thrombin solution before said formation of said fibrin clot. 39. The method as set forth in claim 27, further comprising cutting said fibrin clot after said fibrin clot has been lyophilized. 40. The method as set forth in claim 27, wherein said preparing of said fibrin clot is effected from a sterile starting material, further comprising maintaining sterile conditions throughout said method. 41. A method of treating a patient suffering from wounds and hemorrhages, said method comprising applying to said patient a fibrin sponge having a residual moisture of at least 10%, for at least one of hemostasis, tissue adhesion, cell culture supported healing and wound healing. 42. A kit comprising a storage-stable fibrin sponge having a residual moisture of at least 10% is sterile form for use as a biological support for cell cultures.

Details for Patent 6,548,729

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Baxalta Us Inc.	AUTOPLEX, FEIBA NF, FEIBA VH	anti-inhibitor coagulant complex	For Injection	101447	12/21/1979		2017-09-19
Baxalta Us Inc.	AUTOPLEX, FEIBA NF, FEIBA VH	anti-inhibitor coagulant complex	For Injection	101447	07/31/2000		2017-09-19
Baxalta Us Inc.	AUTOPLEX, FEIBA NF, FEIBA VH	anti-inhibitor coagulant complex	For Injection	101447	08/11/2005		2017-09-19