Thromboresistant surface treatment for biomaterials

• US 5,578,073 A
• Filed: 09/16/1994
• Issued: 11/26/1996
• Est. Priority Date: 09/16/1994
• Status: Expired due to Fees

• Current Assignee: Ramot University Authority For Applied Research and Industrial Development Limited, University of Medicine and Dentistry of New Jersey (State of New Jersey)
• Original Assignee: University of Medicine and Dentistry of New Jersey (State of New Jersey), Ramot at Tel Aviv University Limited (Tel Aviv University)
• Inventors: Greco, Ralph, Haimovich, Beatrice, Freeman, Amihay
• Primary Examiner(s): TSAI, H JEY
• Application Number:
  US08/037,335
• Time in Patent Office: 802 Days
• Field of Search: 623/1, 623/2, 623/16, 524/29, 523/112, 523/113, 523/114, 523/115
• US Class Current: 623/1.48
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61F 2/24 Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
• CPC Class Codes: A61L 33/062 Mixtures of macromolecular compounds
• CPC Class Codes: A61M 1/14 Dialysis systems; Artificial kidneys; Blood oxygenators semi-permeable membranes characterised by the material, manufacturing processes therefor B01D71/00 ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
• CPC Class Codes: A61N 1/36 for stimulation
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08L 5/04 Alginic acid; Derivatives thereof
• 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: C09D 105/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

A biomaterial with a thromboresistant surface and a method for forming same are provided. The thromboresistant surface is comprised of a distinct coating layer of a chitosan-based membrane and a biologically active material. The biologically active material is capable of converting the chitosan membrane coating from a highly thrombogenic to an essentially non-thrombogenic one. The biologically active material can be a polymeric substance, such as polyvinyl alcohol, forming a polymeric blend with the chitosan, or, can be a biological substance, such as serum albumin, embedded in or attached to the chitosan membrane which has been activated with a treatment of glutardialdehyde. The thromboresistant biomaterial is suitable for use in vascular grafts having an inside diameter of less than 6 millimeters.

Claims

1. A biomedical device or prosthesis having a blood contacting surface which has improved antithrombogenic properties and improved strength, which device or prosthesis has a coating which comprises a blend of chitosan and polyvinyl alcohol wherein the biomedical is a homopolymer or a copolymer selected from the group consisting of polytetrafluoroethylenes, polyamides, polyesters, polyurethanes, polysiloxanes, polyolefins, silicone rubber, polyvinyl chlorides, and metals.

2. The biomedical device or prosthesis of claim 1 wherein a portion of the device is tubular.

3. The biomedical device or prosthesis of claim 2 wherein the interior diameter is less than 4 mm.

4. The biomedical device or prosthesis of claim 1 which is selected from the group consisting of catheters, vascular grafts, cardiac pacemakers, pacemaker leads, heart diaphragms, heart valves, sutures, needles, angioplasty devices, tubing, filters, and dialysis membranes.

5. A biomaterial which has improved antithrombogenic properties and improved strength, which biomaterial has a coating which comprises a blend of chitosan and polyvinyl alcohol wherein the biomaterial is a homopolymer or a copolymer selected from the group consisting of polytetrafluoroethylenes, polyamides, polyesters, polyurethanes, polysiloxanes, polyolefins, silicone rubber, polyvinyl chlorides, and metals, which biomaterial is for use in a device or prosthesis having a blood contacting surface.

6. The biomaterial of claim 5 which is a metal.

7. A biomaterial which has improved antithrombogenic properties and which has a coating which comprises chitosan and as a biologically active material which active material is attached to the chitosan at glutaraldehyde-activated free amino sites, human serum albumin.

8. The biomaterial of claim 7 which is a homopolymer or a copolymer selected from the group consisting of polytetrafluoroethylenes, polyamides, polyesters, polyurethanes, polysiloxanes, polyolefins, silicone rubber, polyvinyl chlorides, and metals.

9. A process for treating a biomaterial for use in a biomedical device or prosthesis which has a blood contacting surface, which has improved antithrombogenic properties and improved strength, comprising contacting the surface of the biomaterial with a mixture of a solution of chitosan and polyvinyl alcohol, removing any excess solution, and curing the remaining solution on the surface, thereby obtaining the improved coating, the biomaterial being a homopolymer or a copolymer selected from the group consisting of polytetrafluoroethylenes, polyamides, polyesters, polyurethanes, polysiloxanes, polyolefins, silicone rubber, polyvinyl chlorides, and metals.

10. The process of claim 9 wherein a portion of the biomedical device or prosthesis is tubular with an interior diameter less than 6 mm.

11. A process for treating a biomaterial for use in a biomedical device or prosthesis which has a blood contacting surface and improved antithrombotic properties, comprising contacting the surface of the biomaterial with a chitosan solution, and activating free amino groups on the chitosan by treating the chitosan on the surface of the biomaterial with a solution of glutaraldehyde, wherein the biomaterial is a homopolymer or a copolymer selected from the group consisting of polyamides, polyesters, polyurethanes, polysiloxanes, polyolefins, silicone rubber, polyvinyl chlorides, and metals and treating the activated chitosan with a biologically active material selected from the group consisting of surfactants, antithrombotic agents, antibiotics, and antibodies.

12. The process of claim 11 wherein the biologically active material is human serum albumin.

13. The process of claim 11 wherein a portion of the biomedical device or prosthesis is tubular with an interior diameter less than 6 mm.

14. A polymeric or metal biomedical device or prosthesis having a blood contacting surface which has improved antithrombogenic properties and improved strength, which device or prosthesis has a coating which comprises a blend of chitosan and polyvinyl alcohol, wherein the device or prosthesis has a portion which is tubular of an interior diameter of less than 6 mm.

15. The device or prosthesis of claim 14 wherein the interior diameter of the tubular portion is less than 4 mm.

16. The device or prosthesis of claim 14 which is selected from the group consisting of catheters, vascular grafts, cardiac pacemakers, pacemaker leads, heart diaphragms, heart valves, sutures, needles, angioplasty devices, tubing, filters, and dialysis membranes.

17. The device or prosthesis of claim 14 which is a graft.