Methods for preventing thrombosis; and surgical implant having reduced platelet deposition characteristics

• US 4,909,799 A
• Filed: 09/18/1987
• Issued: 03/20/1990
• Est. Priority Date: 09/18/1987
• Status: Expired due to Fees

• Current Assignee: Jan T. Christenson, Olav Thulesius
• Original Assignee: Jan T. Christenson, Olav Thulesius
• Inventors: Thulesius, Olav, Christenson, Jan T.
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): Rose, Sharon
• Application Number:
  US07/098,472
• Time in Patent Office: 914 Days
• Field of Search: 514/822, 604/265, 604/266, 128/897, 128/898
• US Class Current: 604/265
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61L 33/0041 characterised by the choice of an antithrombatic agent other than heparin heparinoïd A61L33/08; polypeptides A61L33/12

Abstract

In order to improve the surface properties of small caliber vascular grafts or other surgical implants, Forskolin (or a derivative thereof) which is a power cAMP stimulating agent, is applied to the thrombogenic surfaces of the graft/implant. Forskolin as thus used is a potent antiplatelet agent significantly lowering platelet deposition on the implant.

Claims

1. A method for reducing the incidence of thrombosis in a patient following a surgical implant procedure on the patient comprising the steps of:

applying 7B-acetoxy-8,13-epoxy-1a-6B,9a-trihydroxylabd-14-en-11-one (Forskolin) or a derivative thereof to a surgical implant, and

thereafter, implanting the surgical implant with the Forskolin or a derivative thereof thereon into the patient.

2. The method of claim 1 including,

said applying including soaking the surgical implant in the Forskolin or a derivative thereof.

3. The method of claim 2 including,

said soaking including soaking the surgical implant in a solution of the Forskolin or a derivative thereof.

4. The method of claim 3 including,

said solution being an alcohol solution.

5. The method of claim 3 including,

said solution including ethanol.

6. The method of claim 5 including,

said solution being 96% ethanol.

7. The method of claim 3 including,

said solution having a strength of 0.05-0.15% of the Forskolin or a derivative thereof.

8. The method of claim 7 including,

said solution comprising 0.1% alcoholic solution of the Forskolin or a derivative thereof.

9. The method of claim 3 including,

said solution comprising an organic solvent.

10. The method of claim 9 including,

said organic solvent having affinity characteristics to polyurethane or polyethylene.

11. The method of claim 3 including,

said applying including after said soaking, and before said implanting, drying the implant.

12. The method of claim 11 including,

said drying including allowing the implant to dry at room temperature.

13. The method of claim 1 including,

said Forskolin or a derivative thereof comprising 7-0-he-misuccinyl-7-deacety-forskolin.

14. The method of claim 1 including,

said Forskolin or a derivative thereof being chemically bound to polyurethane, polyethylene, or poly-L-lactic acid before being applied to the implant.

15. The method of claim 1 including,

said implant comprising a by-pass graft, an artificial cardiac implant, or a therapeutic arteriovenous shunt.

16. The method of claim 1 including,

said applying including coating the surface of the implant which will be in contact with blood with the Forskolin or a derivative thereof to prevent platelet aggregation thereon.

17. The method of claim 1 further comprising,

applying to the implant an agent that acts synergistically with the Forskolin or the derivative thereof to prevent platelet aggregation.

18. The method of claim 17 including

said agent comprising a prostaglandin.

19. The method of claim 1 including,

said implant comprising a transplant from the patient.

20. The method of claim 19 including,

before said coating, removing the transplant from the patient.

21. The method of claim 20 including,

said transplant comprising an autologous vein graft, and

said Forskolin or a derivative thereof being applied in an isotonic solution.

22. The method of claim 1 including,

said Forskolin or a derivative thereof comprising Forskolin.

24. The method of claim 1 including,

said implant comprising a synthetic vascular graft.

23. A method for preventing undue platelet aggregation on a synthetic vascular graft used in cardiovascular surgery on a patient comprising the steps of:

before implanting the synthetic vascular graft in the patient, applying locally to the graft 7B-acetoxy-8, 13-epoxy-1a-6, 9a-trihydroxylabd-14-en-11-one (Forskolin) or a derivative thereof.

25. An implant device suitable for surgical implantation in a patient and showing low resulting platelet deposition thereon comprising:

a surgical implant having an implant thrombogenic surface, and

a coating of 7B-acetoxy-8,13-epoxy-1a-6B,9a-trihydroxylabd-14-en-11-one (Forskolin) or a derivative thereof on said implant thrombogenic surface.

26. The implant device of claim 25 including,

said coating being applied to said implant thrombogenic surface before said surgical implant is implanted in the patient.

27. The implant device of claim 25 including,

said surgical implant being formed of a synthetic material.

28. The implant device of claim 27 including,

said synthetic material being polytetrafluoroethylene.

29. The implant device of claim 25 including,

said surgical implant comprising a transplant from the patient.

30. The implant device of claim 25 including,

said surgical implant comprising a vascular graft, a cardiac implant, a cardiac assist device, or an artificial device.

31. The implant device of claim 25 including,

said surgical implant comprising an auto-transplanted vessel.

32. The implant device of claim 25 including,

said coating being applied b soaking said implant in a solution of the Forskolin or a derivative thereof and thereafter drying said implant before implanting said implant in the patient.

33. The implant device of claim 25 including,

said surgical implant being a polytetrafloroethylene graft.

34. The implant device of claim 25 including,

said surgical implant comprising a synthetic vascular graft four millimeters or less in diameter and greater than eight centimeters in length.