Anticoagulant plasma polymer-modified substrate

• US 5,455,040 A
• Filed: 11/19/1992
• Issued: 10/03/1995
• Est. Priority Date: 07/26/1990
• Status: Expired due to Term

• Current Assignee: Case Western Reserve University
• Original Assignee: Case Western Reserve University
• Inventors: Marchant, Roger E.
• Primary Examiner(s): Kishore, Gollamudi S.
• Assistant Examiner(s): AZPURU, CARLOS A
• Application Number:
  US07/978,205
• Time in Patent Office: 1,048 Days
• Field of Search: 424/423, 424/426, 514/772.2, 514/772.3, 514/822, 523/112, 523/113, 623/1
• US Class Current: 424/426
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: A61L 33/0094 Physical treatment, e.g. plasma treatment

Abstract

The present invention provides a method for surface modifying a substrate, such as an implant, to provide the substrate with anticoagulant activity and resistance to the deposition of plasma proteins; and the resulting substrate. The surface of the substrate is modified by first depositing a film of a plasma polymer such as plasma polymerized N-vinyl-2-pyrrolidone or allyl alochol on the surface of the substrate. Optionally, a neutral hydrophilic spacer molecule is attached to the plasma polymer. An anticoagulant, such as heparin, is attatched either directly to the substrate or indirectly to the substrate via attatchment to the spacer molecule, when such spacer molecule is present.

Claims

1. A method for reducing the thrombogenicity of a substrate, comprising the steps of:

a. plasma polymerizing polar organic monomers onto the surface of the substrate to provide a plasma polymer film on the surface of the substrate;

b. attaching an a anticoagulant, so that it is bound, directly or indirectly, to the plasma polymer film to provide a substrate having reduced thrombogenicity.

2. The invention of claim 1, wherein the plasma polymer film is comprised of polymerized N-vinyl-2-pyrrolidone.

3. The invention of claim 1, wherein the plasma polymer film is comprised of polymerized allyl alcohol.

4. The invention of claim 1, wherein the anticoagulant is heparin.

5. The invention of claim 1, wherein the anticoagulant is heparin, and plasma polymer film is comprised of polymerized N-vinyl-2-pyrrolidione.

6. The invention of claim 1, wherein the anticoagulant is heparin, and the plasma polymer film is comprised of polymerized allyl alcohol.

7. The invention of claim 1, further comprising the step of attaching a spacer molecule to the plasma polymer film before the step of attaching the anticoagulant.

8. The invention of claim 7, wherein the spacer molecule is 3-aminopropyltriethoxysilane.

9. The invention of claim 7, wherein the spacer molecule is amino-terminated poly(ethyleneoxide).

10. The invention of claim 1, wherein the substrate is nonpolymeric, further comprising the step of first applying a plasma polyhexamethyldisilasane film to the substrate before the step of plasma polymermerizing the organic polar monomers onto the surface of the substrate to provide the plasma polymer film on the polyhexamethyldisilasane film.