Self-aggregating protein compositions and use as sealants

• US 8,231,930 B2
• Filed: 08/04/2009
• Issued: 07/31/2012
• Est. Priority Date: 03/10/1997
• Status: Expired due to Fees

• Current Assignee: Maquet Cardiovascular LLC (Getinge AB)
• Original Assignee: Maquet Cardiovascular LLC (Getinge AB)
• Inventors: Castro, Dan, Kuehn, Al, Sunwoo, Moon Hae
• Primary Examiner(s): Yuan, Dah-Wei
• Assistant Examiner(s): Bowman, Andrew
• Application Number:
  US12/534,937
• Publication Number:
  US 20090297692A1
• Time in Patent Office: 1,092 Days
• Field of Search: 427/2.24, 427/2.25, 427/421.1
• US Class Current: 427/2.25
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 33/08 Polysaccharides
• CPC Class Codes: A61L 33/122 Collagen
• CPC Class Codes: A61L 33/128 Other specific proteins or polypeptides not covered by A61L33/122 - A61L33/126
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin

Abstract

An implantable member for use in the body is provided herein. This implantable member includes a porous biocompatible substrate; the substrate having at least one surface sealed fluid-tight with self-aggregating protein particles of substantially the same diameter range. The self-aggregated protein particles are formed from a deposited aqueous slurry of the protein particles.

Claims

1. A process for making an implantable member for use in the body comprising the steps of:

(a) providing a porous biocompatible substrate having at least one surface;

(b) providing a non-crosslinked sealant composition, said sealant composition comprising self-aggregating purified protein particles of substantially uniform particle size, said protein particles being obtained by cryogenically milling said protein in a purified form suitable for implantation;

(c) applying said sealant composition to at least a portion of said surface of the substrate; and

(d) allowing said sealant composition to dry so as to provide a fluid-tight seal of said portion;

wherein said sealant composition has not been exposed to a cross-linking agent.

2. The process of claim 1, wherein the self-aggregating protein particles have diameters in the range of about 5 μ

m to about 750 μ

m.

3. The process of claim 1, wherein the self-aggregating protein is selected from the group consisting of collagen, fibronectin, vitronectin, proteoglycan, laminin, hyaluronic acid, tenascin, integrin, cadherin and mixtures thereof.

4. The process of claim 1, wherein the self-aggregating protein is collagen.

5. The process of claim 1, wherein the self-aggregating protein particles are formed from cryogenic milling of a paste containing the self-aggregating protein in the purified form.

6. The process of claim 1, wherein the self-aggregating protein particles are formed from a deposited aqueous slurry of between about 1 to about 3% of the protein particles and about 8 to about 30% plasticizer by weight, based on the total weight of the slurry.

7. The process of claim 6, wherein the pH of the slurry is sufficient to maintain the protein particles suspended within the slurry.

8. The process of claim 6, wherein the plasticizer is a polyhydric alcohol.

9. The process of claim 6, wherein the slurry further includes a bio-active agent.

10. The process of claim 9, wherein the bio-active agent is selected from the group consisting of antibiotics, anticoagulants and antibacterial agents.

11. The process of claim 6, wherein the slurry further includes a permeability lowering agent.

12. The process of claim 11, wherein the permeability lowering agent is ethanol.

13. The process of claim 1, wherein said steps of (b) applying said sealant composition to at least a portion of said surface of the substrate and (c) allowing said sealant composition to dry are performed at least three times.

14. The process of claim 1, wherein the substrate is a porous synthetic vascular graft.

15. The process of claim 14, wherein the vascular graft is made from biologically compatible fibers or yarns.

16. The process of claim 15, wherein the fibers or yarns are selected from the group consisting of polyethylene terephthalate and polytetrafluoroethylene.

17. The process of claim 1, wherein said sealant composition is applied to said surface so as to substantially cover the entire surface.