Nonthrombogenic articles having enhanced albumin affinity

• US 4,530,974 A
• Filed: 07/13/1982
• Issued: 07/23/1985
• Est. Priority Date: 03/19/1981
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Munro, Mark S., Eberhart, Robert C., Quattrone, Alfred J., Ellsworth, Steven R.
• Primary Examiner(s): Schofer, Joseph L.
• Assistant Examiner(s): Kulkosky, Peter F.
• Application Number:
  US06/397,885
• Time in Patent Office: 1,106 Days
• Field of Search: 523/112, 525/329.2, 525/329.4, 525/165, 525/178, 525/123
• US Class Current: 525/329.4
• CPC Class Codes: C08J 7/12 Chemical modification

Abstract

Articles having reduced thrombogenicity when in contact with blood products containing albumin and methods of their use are provided. The articles comprise at the surface of blood contact a water insoluble polymeric substrate material having covalently attached thereon aliphatic extensions of 14 to 20 carbon units. When exposed to blood the aliphatic chain extensions provide a hydrophobic binding site for albumin. The articles when implemented with whole blood or blood products selectively enhance albumin affinity binding to the exclusion of other blood components, and subsequently minimize thrombus formation.

Claims

1. A nonthrombogenic article adapted for use in contact with blood or blood products containing albumin, said article having on those surfaces which contact blood or blood products a water soluble, biocompatible, nonionic polymeric substrate having covalently attached thereon nonionic, aliphatic hydrocarbon extensions of 14 to 20 carbon atoms, the degree of aliphatic extension attachment effective to absorb albumin sufficient to retard thrombus formation on said surfaces.

2. The article of claim 1 wherein the aliphatic extensions are straight chained radicals.

3. The article of claim 1 wherein the aliphatic extensions are alkyl radicals.

4. The article of claim 1 wherein the aliphatic extensions are olefinic radicals.

5. The article of claims 2, 3 or 4 wherein the aliphatic extensions have 18 carbon atoms.

6. The article of claims 1 or 2 wherein the aliphatic extensions are myristryl, cetyl, octadecyl, arachidyl, oleyl or linoleyl or linolenyl.

7. The article of claim 1 wherein the polymeric substrate is polyurethane, polyamide, polyamine, polyacrylamide, polyimine, polyester, cellulosic, amino-modified polystyrenes or amino-substituted polyesters.

8. The article of claim 1 wherein the polymeric substrate provides an amino or imino functional group for the covalent binding site of the aliphatic hydrocarbon extentions.

9. The article of claim 1 wherein the polymeric substrate is structurally stable.

10. The article of claim 1 which further comprises albumin adsorbed to the hydrocarbon extensions.

21. The article of claim 1 which is vascular graft tubing, dialysis tubing or membrane, blood oxygenator tubing or membrane, intra-aortic balloon, ultrafiltration membrane, blood bag, catheter, suture, soft or hard tissue prosthesis, or artificial organ.

11. A method for rendering nonthrombogenic at least one surface of article adapted for use in contact with bood or blood products containing albumin, comprising

establishing on said article surface a water insoluble biocompatible, nonionic polymer substrate having thereon abstractable hydrogen sites effective for covalent attachment,

alkylating said substrate at said hydrogen sites with aliphatic hydrocarbon extensions of 14 to 20 carbon atoms, the degree of aliphatic extension attachment effective to provide a nonionic affinity binding site for an amount of albumin sufficient to retard thrombus formation on said surface.

12. The method of claim 11 wherein the aliphatic extensions are straight chained radicals.

13. The method of claim 11 wherein the aliphatic extensions are alkyl radicals.

14. The method of claim 11 wherein the aliphatic extensions are olefinic radicals.

15. The method of claims 12, 13 or 14 wherein the aliphatic extensions have 18 carbon atoms.

16. The method of claims 11 or 12 wherein the aliphatic extensions are myristryl, cetyl, octadecyl, arachidyl, oleyl, linoleyl or linolenyl.

17. The method of claim 11 wherein the polymeric substrate is polyurethane, polyamide, polyamine, polyacrylamide, polyimine, polyester, cellulosic, amino-modified polystyrene or amino-substituted polyesters.

18. The method of claim 11 wherein the polymeric substrate provides an amino or imino functional group for the covalent binding site of the aliphatic hydrocarbon extensions.

19. The method of claim 11 wherein the polymeric substrate is structurally stable.

20. The method of claim 11 which further comprises albumin adsorbed to the hydrocarbon extensions.

22. The method of claim 11 wherein the article adapted for use in contact with blood or blood products is vascular graft tubing, dialysis tubing or membrane, blood oxygenator tubing or membrane, intra-aortic balloon, ultrafiltration membrane, blood bag, catheter, suture, soft or hard tissue prosthesis, or artificial organ.