Biocompatible materials

• US 5,711,959 A
• Filed: 09/10/1996
• Issued: 01/27/1998
• Est. Priority Date: 03/17/1995
• Status: Expired due to Term

• Current Assignee: Regents of The University of Minnesota (University of Minnesota)
• Original Assignee: Regents of The University of Minnesota (University of Minnesota)
• Inventors: Kohler, Anja S., Furcht, Leo T., Mooradian, Daniel L.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/707,954
• Time in Patent Office: 504 Days
• Field of Search: 424/423, 514/822, 523/112, 523/113
• US Class Current: 424/423
• CPC Class Codes: A61L 33/0082 by reacting with an organic compound other than heparin

Abstract

A biocompatible material comprising a substrate and a phospholipid moiety covalently attached thereto in an amount and orientation effective to provide an improved nonthrombogenic surface relative to the substrate without the phospholipid moiety covalently attached thereto is provided. In particularly preferred embodiments, the biocompatible material has the following structure: ##STR1## wherein: R¹ is a (C₁ -C₃₀)alkyl group; R² is a (C₁ -C₃₀)alkylene group; m is 1-4; n is 1-4; and L is a divalent linking group covalently bonded to the substrate and to the phospholipid moiety.

Claims

1. A biocompatible material comprising a substrate and a phospholipid moiety covalently attached thereto in an amount and orientation effective to provide an improved nonthrombogenic surface relative to the substrate without the phospholipid moiety covalently attached thereto, wherein the biocompatible material has the following structure:

##STR8## wherein;

(a) R¹ is a (C₁ -C₃₀)alkyl group;

(b) R² is a (C₁ -C₃₀)alkylene group;

(c) m is 1-4;

(d) n is 1-4; and

(e) L is --C(O)--NH--(CH₂)_p -- wherein p is 0-20.

2. The biocompatible material of claim 1 wherein:

(a) R¹ is a (C₁₂ -C₂₀)alkyl group;

(b) R² is a (C₄ -C₁₀)alkylene group;

(c) m is 1; and

(d) n is 1.

3. The biocompatible material of claim 1 wherein L is --C(O)--NH--(CH₂)_p -- wherein p is 1-6.

4. The biocompatible material of claim 1 wherein the substrate is an organic polymer.

5. The biocompatible material of claim 4 wherein the organic polymer is selected from the group consisting of polypropylene and polytetrafluoroethylene.

6. A medical device comprising the biocompatible material of claim 1.

7. A method for enhancing the biocompatibility of a substrate comprising:

(a) covalently attaching a phospholipid compound to the substrate with a linker of the formula --C(O)--NH--(CH₂)_p --, wherein p is 0-20, in an amount and orientation effective to provide an improved nonthrombogenic surface relative to the substrate without the phospholipid moiety covalently attached thereto; and

(b) contacting the substrate with blood;

wherein the phospholipid moiety has the following structure;

##STR9## wherein;

(a) R³ is a (C₁ -C₃₀)alkyl group having 0-4 double bonds;

(b) R⁴ is a (C₁ -C₃₀)alkyl group having 0-4 double bonds;

(c) m is 1-4;

(d) n is 1-4; and

(e) either R³ or R⁴ has at least one double bond.

8. The method of claim 7 wherein the substrate is an aminated substrate and the phospholipid compound is covalently attached to the aminated substrate by:

(a) oxidizing the at least one double bond in R³ or R⁴ of the phospholipid compound to form a carboxylated phospholipid; and

(b) combining the carboxylated phospholipid with the animated substrate and a carboxyl-reactive crosslinker to form an amide linkage and covalently attach the phospholipid to the substrate.

9. The method of claim 8 wherein the carboxyl-reactive crosslinker is selected from the group consisting 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride, N,N'"'"'-dicyclohexylcarbodiimide, 4-(p-azidosalicylamido)-butylamine, and diisopropylcarbodiimide.

10. The method of claim 7 wherein the substrate is an organic polymer.

11. The method of claim 10 wherein the organic polymer is selected from the group consisting of polypropylene and polytetrafluoroethylene.

12. The method of claim 10 wherein the substrate having improved biocompatibility is contained in a medical device.

13. A biocompatible material comprising a substrate and a phospholipid moiety covalently attached thereto in an amount and orientation effective to provide an improved nonthrombogenic surface relative to the substrate without the phospholipid moiety covalently attached thereto, having the following structure:

##STR10## wherein;

(a) R¹ is a (C₁ -C₂₀) alkyl group;

(b) R² is a (C₄ -C₁₀) alkylene group;

(c) m is 1;

(d) n is 1; and

(e) L is --C(O)--NH--(CH₂)_p -- wherein p is 1-6.