Process for reducing the thrombogenicity of biomaterials

• US 5,417,969 A
• Filed: 11/18/1993
• Issued: 05/23/1995
• Est. Priority Date: 09/20/1991
• Status: Expired due to Fees

• Current Assignee: Edwards Lifesciences Corporation
• Original Assignee: Baxter International Inc.
• Inventors: Farhat, Lawrence, Balding, David P., Hsu, Li-Chien
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Kulkosky, Peter F.
• Application Number:
  US08/154,654
• Time in Patent Office: 551 Days
• Field of Search: 424/78.08, 424/78.27, 424/78.17, 424/423, 424/78.1, 522/126, 528/488
• US Class Current: 424/78.27
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: A61L 33/0017 using a surface active agent

Abstract

Processes for forming a uniform, continuous coating of heparin covalently bonded to blood-contacting polyvinylchloride surfaces of a medical device are disclosed. These processes include coating the polyvinylchloride surfaces with an organic solvent solution of heparin complexed with an organic cation, and then exposing the coated surfaces to ionizing radiation to covalently bind the heparin moiety to the polyvinylchloride. The complex of the coating is formed from a heparin moiety and at least one cationic moiety selected from the group consisting of dimethylstearylamine, polyethyleneimine, benzalkonium, stearylkonium, and tridodecylmethylammonium; the complex is soluble in organic solvents and forms continuous and uniform coatings on polyvinylchloride. Advantageously, the heparin moiety can be bonded to the polyvinylchloride surfaces simultaneously with sterilizing the medical devices using ionizing radiation.

Claims

1. A process for reducing the surface thrombogenicity of a medical device having at least one polyvinylchloride surface, said process comprising the steps of:

providing a solution in an organic solvent of a complex of an anionic heparin moiety and a cationic organic moiety selected from the group consisting of dimethylstearylamine, polyethyleneimine, benzalkonium ion, stearylkonium ion, and tridodecylmethylammonium ion;

depositing from said solution a uniform and continuous film of said complex upon a polyvinylchloride surface of a medical device; and

exposing the polyvinylchloride surface having said film deposited thereon to a sufficient dose of ionizing radiation to form covalent bonds between said complex and said polyvinylchloride surface.

2. The process of claim 1 wherein said complex is present in said organic solvent in a concentration of about 0.01 wt % to about 10 wt % of said solution.

5. The process of claim 1 wherein said dose of ionizing radiation is at least 0.1 megarad.

6. The process of claim 1 further including the step, after exposing to ionizing radiation, of contacting said complex covalently bound to said polyvinylchloride surface with an aqueous salt solution having an ionic strength sufficiently high to exchange said cationic organic moiety with a cation of said aqueous salt solution.

7. The process of claim 6 further including the step of sterilizing said medical device.

10. An antithrombogenic medical device prepared according to the process of claim 1.

3. A process for simultaneously sterilizing a medical device and covalently binding heparin to a blood-contacting polyvinylchloride surface of a medical device, said process comprising the steps of:

providing a solution in an organic solvent of a complex of an anionic heparin moiety and a cationic organic moiety selected from the group consisting of dimethylstearylamine, polyethyleneimine, benzalkonium ion, stearylkonium ion, and tridodecylmethylammonium ion;

depositing from said solution a uniform and continuous film of said complex upon a polyvinylchloride surface of a medical device;

allowing said organic solvent to vaporize; and

exposing the medical device having said film deposited thereon to a sufficient dose of ionizing radiation to form covalent bonds between said complex and said polyvinylchloride surface and to sterilize said medical device.

4. The process of claim 3 wherein said complex is present in said organic solvent in a concentration of about 0.01 wt % to about 10 wt % of said solution.

8. The process of claim 3 wherein said dose of ionizing radiation is at least 1.5 megarad.

9. The process of claim 3 further including the step of packaging said medical device in sterile packaging subsequent to allowing said organic solvent to vaporize.

11. An antithrombogenic medical device prepared according to the process of claim 3.