Claims for Patent: 5,256,418

Summary for Patent: 5,256,418

Title:	Collagen constructs
Abstract:	The present invention provides collagen constructs and methods of making and using such constructs. The present invention also provides tissue equivalents having improved characteristics and methods of making and using such tissue equivalents. This invention also provides methods of producing highly concentrated solutions of collagen.
Inventor(s):	Kemp; Paul D. (Cambridge, MA), Carr, Jr.; Robert M. (Boston, MA), Maresh; John G. (Cambridge, MA)
Assignee:	Organogenesis, Inc. (Canton, MA)
Application Number:	07/505,678
Patent Claims:	1. A method of forming a construct comprising collagen, the method comprising the steps of: (a) providing an aqueous solution comprising collagen adjacent a permeable member, the permeable member being substantially impermeable to collagen and in contact with a concentrating agent, wherein the concentrating agent has an osmotic pressure higher than that of the collagen solution and permits selective mass transfer of solvent from the collagen solution through the permeable member; and (b) maintaining the collagen solution, permeable member and concentrating agent under conditions sufficient to enable the selective mass transfer of solvent from the collagen solution and the formation of the collagen construct at the permeable member. 2. The method of claim 1, further comprising the step of causing fibrils to form in the collagen construct. 3. The method of claims 1 or 2, wherein the concentrating agent comprises a water-soluble polymer. 4. The method of claim 3, wherein the concentrating agent comprising at least one of polyethylene glycol and dextran. 5. The method of claim 3, wherein the concentrating agent comprises a polymer in phosphate buffered saline. 6. The method of claim 5, wherein the concentrating agent comprises a solution of polyethylene glycol or dextran in sodium chloride. 7. The method of claim 6, wherein the concentrating agent comprises a solution of 20% weight/volume polyethylene glycol having a molecular weight of about 8000 in phosphate buffered saline. 8. The method of claim 2, wherein the concentrating agent comprises a polymer in phosphate buffered saline, and the fibrils are caused to form by means of increasing the pH and ionic strength of the concentrating agent. 9. The method of claims 1 or 2, wherein the collagen concentration of the construct is about 50 to 100 mg/ml. 10. The method of claims 1 or 2, wherein the collagen concentration of the construct is at least about 100 mg/ml. 11. The method of claims 1 or 2, wherein the permeable member comprises a membrane. 12. The method of claim 11, wherein the membrane comprises a porous ceramic or stainless steel material, dialysis tubing, or a nucleopore membrane. 13. The method of claims 1 or 2, wherein the permeable member is flat or tubular. 14. The method of claims 1 or 2, further comprising the step of providing cells to the collagen construct. 15. The method of claim 14, wherein the cells are at least one of endothelial and epithelial cells. 16. The method of claims 1 or 2, further comprising the step of forming pores in the collagen construct. 17. The method of claim 16, wherein pores are formed by lyophilyzing the collagen construct. 18. The method of claim 16, wherein the pores are formed by means of incorporating a polymer in the collagen construct and the method further comprises the step of removing the polymer from the collagen construct. 19. The method of claim 18, wherein the polymer is polyvinyl alcohol or hyaluronic acid. 20. The method of claim 2, further comprising the step of cross-linking the fibrils in the collagen construct. 21. The method of claim 20, wherein the fibrils are cross-linked by air-drying, lyophilizing or contact with an aldehyde. 22. The method of claim 20, wherein the collagen construct has a burst strength of about 300 to 1000 mm Hg. 23. The method of claim 20, wherein the collagen construct has a burst strength of greater than 1000 mm Hg. 24. The method of claims 1 or 2, wherein the collagen solution is at a concentration of about 5 to 10 mg/ml collagen and a pH of about 2 to 4. 25. The method of claims 1 or 2, wherein the collagen construct is provided with a support member. 26. The method of claim 25, wherein the support member comprises a polyester. 27. The method of claims 1 or 2, wherein the collagen solution further comprises at least one of an angiogenic factor, an anti-inflammatory agent, a chemotactic agent, or a collagenase inhibitor. 28. A method of forming a tubular collagen construct in accordance with claims 1 or 2 by use of a device having an inner and outer chamber, the interface between the inner and outer chamber comprising a tubular permeable member, the method comprising the steps of: (a) providing the solution comprising collagen the outer chamber; (b) providing the concentrating agent to the inner chamber; and (c) maintaining the collagen solution, permeable member and concentrating agent under conditions sufficient to enable the collagen construct to form at the permeable member. 29. A method of forming a tubular collagen construct in accordance with claims 1 or 2 by use of device having an inner and outer chamber, the interface between the inner and outer chamber comprising a tubular permeable member, the method comprising the steps of: (a) providing the solution comprising collagen to the inner chamber; (b) providing the concentrating agent to the outer chamber; and (c) maintaining the collagen solution, permeable member and concentrating agent under conditions sufficient to enable the collagen construct to form at the permeable member. 30. A method of forming a multi-layer tubular collagen chamber, the interface between the inner and outer chamber comprising a tubular permeable member, the method comprising the steps of: (a) providing a first solution comprising collagen at a pH of about 2 to 4 to the outer chamber; (b) providing a concentrating agent to the inner chamber; (c) maintaining the first collagen solution, permeable member and concentrating agent under conditions sufficient to enable the tubular collagen construct to form at the permeable member; (d) replacing the first collagen solution with a second solution comprising collagen; and (e) maintaining the second collagen solution, permeable member and concentrating agent under conditions sufficient to enable a second tubular construct to form outwardly of the first tubular construct; and (f) repeating steps (d) and (e) if additional layers of tubular collagen construct are desired. 31. The method of 30, further comprising the step of causing fibrils to form in at least one layer of the collagen construct. 32. A method of forming a flat collagen construct by use of a device having an inner and outer container, the interface between the inner and outer chamber comprising a flat permeable member, the method comprising the steps of: (a) providing a solution comprising collagen to the inner chamber; (b) providing a concentrating agent to the outer chamber; and (c) maintaining the collagen solution, permeable member and concentrating agent under conditions sufficient to enable the flat construct to form at the permeable member. 33. A method of concentrating a solution of collagen comprising: (a) contacting a collagen solution with a permeable member, the permeable member being in contact with an agent for concentrating the collagen; (b) maintaining the collagen solution and concentrating agent under conditions sufficient to enable the collagen solution to reach a concentration of, from about 50 to 100 mg/ml. 34. The method of claim 33, wherein the collagen solution reaches a concentration of about 100 mg/ml.

Details for Patent 5,256,418

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2039-03-29