Methods for immobilizing anti-thrombogenic material onto a medical device or into a coating thereon

• US 8,263,170 B2
• Filed: 01/06/2010
• Issued: 09/11/2012
• Est. Priority Date: 07/30/2001
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Michal, Eugene T., Ding, Ni, Buchko, Christopher
• Primary Examiner(s): Meeks, Timothy
• Assistant Examiner(s): SELLMAN, CACHET I
• Application Number:
  US12/683,404
• Publication Number:
  US 20100173065A1
• Time in Patent Office: 979 Days
• Field of Search: 427/2.1, 427/2.24, 427/2.25, 623/1.42, 623/1.44, 623/1.46
• US Class Current: 427/2.24
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: A61L 33/0088 by grafting of a monomer onto the substrate

Abstract

The present invention is directed to a medical device having a polymerized base coat layer for the immobilization of an anti-thrombogenic material, such as heparin, thereon. The binding coat layer is comprised of various chemically functional groups which are stable and allow for the immobilization of the anti-thrombogenic material thereto. Methods for immobilizing the anti-thrombogenic material within the base coat layer posited on a surface of the medical device are also provided.

Claims

1. A method for immobilizing an anti-thrombogenic material onto a coating deposited on a surface of an implantable medical device, the method comprising:

preparing a base coat mixture for application to the surface of the medical device, the surface of the implantable medical device optionally coated with a primer layer;

applying the base coat mixture to the surface of the medical device;

polymerizing the base coat mixture to form a base coat layer on the medical device, the base coat layer comprising chemically functional groups;

performing a reaction between the chemically functional groups of the base coat layer and excess amine-terminated material;

rinsing the base coat layer with water; and

performing a reaction between the anti-thrombogenic material and amine-terminated material on the surface of the medical device;

wherein the amine-terminated material is amine-terminated hyaluronic acid or amine-terminated polyvinyl pyrrolidone.

2. The method of claim 1, wherein the reaction between the excess amine-terminated material and the chemically functional groups within the base coat layer runs for about eighteen to twenty-four hours at a temperature in the range of 15°

C. to 80°

C. and about pH 7.0.

3. The method of claim 2, wherein the excess amine-terminated material is amine-terminated polyvinyl pyrrolidone.

4. The method of claim 3, wherein the concentration of the amine-terminated material is about 0.01 mg/ml to 20 mg/ml.

5. The method of claim 1, wherein the anti-thrombogenic material is unfractionated heparin.

6. The method of claim 5, wherein unfractionated heparin is reacted with amine terminated material and a water-soluble carbodiimide on the surface of the medical device for the immobilization of heparin thereon.

7. The method of claim 6, wherein the reaction between unfractionated heparin and amine-terminated material with the water soluble carbodiimide on the surface of the medical device runs for about two to six hours at about room temperature and about pH 4.5 to 7.5.

8. The method of claim 1, wherein the anti-thrombogenic material is N-desulfated heparin.

9. The method of claim 8, wherein N-desulfated heparin is reacted with amine terminated material and a water-soluble carbodiimide on the surface of the medical device for the immobilization of heparin thereon.

10. The method of claim 9, wherein the reaction between N-desulfated heparin and amine-terminated material with the water soluble carbodiimide on the surface of the medical device runs for about two to six hours at about room temperature and about pH 4.5 to 7.5.

11. An implantable medical device comprising

a coating deposited on a surface of the implantable medical device, the coating comprising an anti-thrombogenic material attached to the coating by the method of claim 1.

12. The method of claim 1, wherein the excess amine-terminated material is amine-terminated hyaluronic acid.