Claims for Patent: 5,120,833

Summary for Patent: 5,120,833

Title:	Method of producing grafts
Abstract:	A unique method (10) for preparing protein-impacted grafts (22) wherein an untreated graft (22) is impacted and impregnated with a protein solution, ideally a collagen suspension (14) utilizing a dynamic flow soaking process (24). After soaking in the dynamic flow (24), the collagen-impacted graft is thermally and chemically fixed (26). Following a water wash (30) and glycine wash (34), the graft (22) is softened with a plastification procedure (36), after which it is air dried (38) and placed in a package and sterilized. With the method of the present invention, storable, surgically-ready collagen-impacted grafts can be reliably and rapidly prepared with a high degree of control and uniformity of characteristics in each graft than has heretofore been possible.
Inventor(s):	Kaplan; Alexander (Mountlake Terrace, WA)
Assignee:
Application Number:	07/669,920
Patent Claims:	1. A method of producing a protein-impacted graft, comprising the steps of: soaking an untreated graft in a flow of protein suspension; gelling the exterior surface of the protein-soaked graft by exposing the graft to a subfreezing temperature; fixing the protein in the graft; washing the graft; softening the graft; and drying the graft. 2. The method of claim 1, wherein the step of softening the graft comprises the step of soaking the graft in a softening solution. 3. The method of claim 1, wherein the step of soaking the graft in a flow of protein suspension further includes the step of preparing a suspension of protein. 4. The method of claim 1, wherein the step of washing the graft comprises the steps of washing the graft in sterile water and washing the graft in a chemical solution. 5. A method of producing a collagen graft from an untreated graft that was previously formed of a fibrous material into a tubular shape, comprising the steps of: impacting the untreated graft with a collagen suspension; thermally fixing the collagen-impacted graft by placing the collagen-impacted graft in a subfreezing environment to gel the collagen on the surface of the collagen-impacted graft; chemically fixing the collagen-impacted graft; softening the collagen-impacted graft; and air drying the collagen-impacted graft. 6. The method of claim 5, wherein the step of impacting the graft comprises the step of soaking the graft in a dynamic flow of collagen suspension. 7. The method of claim 5, wherein the step of chemically fixing the collagen-impacted graft comprises soaking the collagen-impacted graft in a formaldehyde solution. 8. The method of claim 7, wherein the collagen-impacted graft is soaked in formaldehyde for at least one hour. 9. The method of claim 8, wherein the step of chemically fixing the collagen-impacted graft includes the further step of soaking the collagen-impacted graft in sterile water. 10. The method of claim 9, wherein the collagen-impacted graft is soaked in sterile water for at least one hour. 11. The method of claim 6, comprising the further step of washing the collagen-impacted graft in a glycine solution. 12. The method of claim 11, wherein the collagen-impacted graft is washed in a glycine solution for at least one hour. 13. The method of claim 12, wherein the step of washing the collagen-impacted graft includes the further step of determining the presence of free aldehydes in the glycine solution after the collagen-impacted graft has been washed. 14. The method of claim 6, wherein the step of softening the collagen-impacted graft comprises soaking the collagen-impacted graft in a glycerin solution. 15. The method of claim 14, wherein the collagen-impacted graft is soaked in said glycerin solution for at least one hour. 16. A method of producing a storable, surgically-ready collagen-impacted graft from an untreated graft, comprising the steps of: preparing a collagen suspension; soaking the untreated graft in a dynamic flow of collagen suspension; thermally gelling the collagen on the surface of the collagen-impacted graft by exposing the graft to a subfreezing temperature; chemically fixing the collagen in the collagen-impacted graft; washing the collagen-impacted graft; soaking the collagen-impacted graft in a softening solution; air drying the collagen-impacted graft; and packaging the collagen-impacted graft. 17. The method of claim 16, wherein said step of preparing a collagen suspension comprises the step of first preparing a buffer solution. 18. The method of claim 17, wherein the step of preparing a buffer solution comprises mixing sodium acetate with sodium chloride in sterile water. 19. The method of claim 18, wherein the ratio of sodium acetate is in the range of 0.5% to 25% w/v and the ratio of sodium chloride is in the range of 0.5% to 25% w/v. 20. The method of claim 19, wherein the step of preparing a suspension of collagen further includes the step of blending type 1 bovine fibrous collagen with the buffer solution in a blender to form a mixture. 21. The method of claim 20, wherein said step of preparing a suspension of collagen includes a further step of separating a collagen suspension from the mixture. 22. The method of claim 20, wherein said step of soaking an untreated graft in a dynamic flow of collagen suspension comprises mounting the graft in an apparatus and subjecting the graft to a longitudinal flow of collagen suspension. 23. The method of claim 22, wherein the step of thermally gelling the collagen on the exterior surface of the collagen-impacted graft comprises placing the collagen-impacted graft in a freezer to expose said graft to subfreezing temperatures. 24. The method of claim 23, wherein the graft is exposed to subfreezing temperatures for a period of time in the range of ten minutes to fifteen minutes. 25. The method of claim 23, wherein the step of chemically fixing the collagen in the collagen-impacted graft comprises the step of preparing a formaldehyde solution. 26. The method of claim 25, wherein the step of preparing the formaldehyde solution comprises the steps of mixing formaldehyde and sterile water. 27. The method of claim 26, wherein the ratio of formaldehyde is in the range of 0.5% to 20% v/v. 28. The method of claim 27, wherein said step of fixing the collagen in the collagen-impacted graft comprises the further step of soaking said thermally-gelled collagen-impacted graft in the formaldehyde solution. 29. The method of claim 28, wherein the graft is soaked in the formaldehyde solution for at least one hour. 30. The method of claim 28, wherein the step of chemically washing the collagen-impacted graft comprises soaking the collagen-impacted graft in sterile water. 31. The method of claim 30, wherein the graft is soaked in sterile water for at least one hour. 32. The method of claim 30, wherein the step of chemically washing the collagen-impacted graft comprises the further step of soaking the graft in a glycine solution. 33. The method of claim 32, wherein the graft is washed for at least one hour. 34. The method claim 33, wherein the step of chemically washing the collagen-impacted graft comprises the further step of testing the glycine solution after the collagen-impacted graft has soaked for the presence of free aldehyde groups. 35. The method of claim 32, wherein said step of softening the collagen-impacted graft comprises a first step of preparing a glycering solution. 36. The method of claim 35, wherein the step of preparing the glycerin solution comprises mixing glycerin in sterile water. 37. The method of claim 36, wherein the concentration of glycerin exceeds 10% v/v. 38. The method of claim 35, wherein said step of softening the collagen-impacted graft comprises the further step of soaking the collagen-impacted grafts in the glycerin solution. 39. The method of claim 38, wherein the graft is soaked in the glycerin solution for at least one hour. 40. The method of claim 38, wherein said step of air drying the collagen-impacted grafts comprises placing the collagen-impacted graft in a sterile environment and allowing to air dry. 41. The method of claim 40, wherein the graft is allowed to dry for at least twelve hours.

Details for Patent 5,120,833

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2039-09-23