US 6,509,104 B2 · Antithrombogenic polymer coating

Abstract

An article having a non-thrombogenic surface and a process for making the article are disclosed. The article is formed by (i) coating a polymeric substrate with a crosslinked chemical combination of a polymer having at least two amino substituted side chains, a crosslinking agent containing at least two crosslinking functional groups which react with amino groups on the polymer, and a linking agent containing a first functional group which reacts with a third functional group of the crosslinking agent, and (ii) contacting the coating on the substrate with an antithrombogenic agent which covalently bonds to a second functional group of the linking agent. In one example embodiment, the polymer is a polyamide having amino substituted alkyl chains on one side of the polyamide backbone, the crosslinking agent is a phosphine having the general formula (A)3P wherein A is hydroxyalkyl, the linking agent is a polyhydrazide and the antithrombogenic agent is heparin.

Claims55

Dependent claims

A process for rendering the surface of a substrate non-thrombogenic, the process comprising:

(a) providing a polymer having side chains along a backbone forming the polymer, at least two of the side chains containing an amino group;
(b) mixing the polymer with a crosslinking agent and a linking agent to produce a polymer solution, the crosslinking agent containing at least two crosslinking functional groups that react with the amino groups, and the linking agent containing a first functional group and a second functional group, the first functional group reacting with a third functional group of the crosslinking agent;
(c) providing a substrate;
(d) coating at least a portion of the substrate with the polymer solution to produce a crosslinked polymer coating on the substrate;
and
(e) contacting at least a portion of the crosslinked polymer coating on the substrate with an antithrombogenic agent whereby the antithrombogenic agent covalently bonds to the second functional group of the linking agent.

3 more elements

A process for rendering the surface of a substrate non-thrombogenic, the process comprising:

(a) reacting a monomer selected from unsaturated carboxylic acids, esters of unsaturated carboxylic acids, anhydrides of unsaturated carboxylic acids, and mixtures thereof, and a first amine to form an intermediate reaction product, wherein the first amine is selected from RR1NH, RNH2, RR1NH2+, RNH3+ and mixtures thereof, wherein R and R1 can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof;
(b) reacting the intermediate reaction product and a second amine to form a polyamide, wherein the second amine is selected from R2R3NH, R2NH2, R2R3NH2+, R2NH3+ and mixtures thereof, wherein R2 and R3 can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, wherein multiple of the R, R1, R2, and R3 are in vertically aligned spaced relationship along a backbone formed by the polyamide and at least two side chains of the polyamide contain an amino group;
(c) mixing the polyamide with a crosslinking agent selected from the group consisting of phosphines having the general formula (A)3P, wherein A is hydroxyalkyl, and with a linking agent having two functional groups of the formula —CONHNH2 to produce a polymer solution;
(d) providing a substrate;
(e) coating at least a portion of the substrate with the polymer solution to produce a crosslinked polymer coating on the substrate;
and
(f) contacting at least a portion of the crosslinked polymer coating on the substrate with heparin whereby the heparin covalently bonds to the second functional group of the linking agent.

4 more elements

A process for rendering the surface of a substrate non-thrombogenic, the process comprising:

(a) reacting an α,β-unsaturated lactone and a first amine to form an intermediate reaction product, wherein the first amine is selected from RR1NH, RNH2, RR1NH2+, RNH3+ and mixtures thereof, wherein R and R1 can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof;
(b) reacting the intermediate reaction product and a second amine to form a polyamide, wherein the second amine is selected from R2R3NH, R2NH2, R2R3NH2+, R2NH3+ and mixtures thereof, wherein R2 and R3 can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, wherein multiple of the R, R1, R2, and R3 are in vertically aligned spaced relationship along a backbone formed by the polyamide and at least two side chains of the polyamide contain an amino group;
(c) mixing the polyamide with a crosslinking agent selected from the group consisting of phosphines having the general formula (A)3P, wherein A is hydroxyalkyl, and with a linking agent having two functional groups of the formula —CONHNH2 to produce a polymer solution;
(d) providing a substrate;
(e) coating at least a portion of the substrate with the polymer solution to produce a crosslinked polymer coating on the substrate;
and
(f) contacting at least a portion of the crosslinked polymer coating on the substrate with heparin whereby the heparin covalently bonds to the second functional group of the linking agent.

4 more elements

An article having a non-thrombogenic surface, the article comprising:

a substrate;
a coating disposed on at least a portion of the substrate, the coating comprising a crosslinked chemical combination of (i) a polymer having side chains along a backbone forming the polymer, at least two of the side chains containing an amino group, (ii) a crosslinking agent containing at least two functional groups that react with the amino groups, and (iii) a linking agent containing a first functional group and a second functional group, the first functional group reacting with a third functional group of the crosslinking agent;
and
an antithrombogenic agent covalently bonded to the second functional group of the linking agent.

1 more element

Dependencies are inferred from the claim text.

Antithrombogenic polymer coating

Life of this patent

Antithrombogenic polymer coating

Life of this patent

Abstract

Claims55