Steroid lipid-modified polyurethane as an implantable biomaterial, the preparation and uses thereof

1. A process for preparing a modified polyurethane comprising a lipid substituent pendant from at least one urethane nitrogen and/or at least one carbon atom of the modified polyurethane, the process comprising:

providing a polyurethane comprising a urethane amino moiety and at least one carbon; providing a multifunctional linker reagent of a formula:

LG-R L -(FG) n

wherein n is an integer from 1 to 3, FG is a functional group selected from the group consisting of a halogen, a carboxyl group, a sulfonate ester, and an epoxy group, LG is a leaving group selected from the group consisting of a halogen, a carboxyl group, a sulfonate ester, and an epoxy group, and R L is an (n+1)-valent organic radical comprising at least one carbon atom;

providing a lipid comprising the lipid substituent;

reacting the multifunctional linker reagent with the urethane amino moiety to form a polyurethane substituted with at least one substituent group of a formula

—R L -(FG) n ; and

reacting the lipid and the polyurethane substituted with the at least one substituent group to form the modified polyurethane;

wherein the lipid comprises a steroid lipid and the lipid substituent comprises a steroid lipid substituent;

wherein the steroid lipid comprises modified cholesterol and the steroid lipid substituent is a thiol-modified cholesterol substituent;

wherein the modified cholesterol is prepared by contacting a cholesterol with at least one reactant to provide at least one substituent group on the modified cholesterol, wherein the substituent group is a thiol group; and

wherein the modified cholesterol is a thiol modified cholesterol and wherein the step of treating the cholesterol with at least one reactant comprises treating the cholesterol with epihalohydrin to yield a glycidyl modified cholesterol and treating the glycidyl modified cholesterol with a thiolating agent.

2. The process of claim 1 , wherein R L is a bivalent organic radical selected from the group consisting of C 1 to C 18 alkylene, C 1 to C 18 alkyleneamino, C 1 to C 18 alkyleneoxy, C 1 to C 18 haloalkylene, C 2 to C 18 alkenylene, C 6 to C 18 arylene, a modified C 2 to C 18 alkenylene having at least one carbon substituted by a halogen group, C 2 to C 18 alkenylene having one or more O, S, or N atoms incorporated into an alkenylene chain, a bivalent heterocyclic radical, and mixtures thereof.

3. The process of claim 2 , wherein the multifunctional linker reagent is a member selected from the group consisting of a dibromoalkyl compound, a bromo-carboxyalkyl compound, and a bromo-epoxyalkyl compound.

4. The process of claim 1 , wherein the modified cholesterol comprises 3-mercapto-2-hydroxypropyl-cholesterol.

5. A process for preparing a modified polyurethane comprising a lipid substituent pendant from at least one urethane nitrogen and/or at least one carbon atom of the modified polyurethane, the process comprising:

reacting a steroid lipid with epihalohydrin to yield a glycidyl derivative of the steroid lipid;

reacting the glycidyl derivative of the steroid lipid with a thiolating agent, thereby effecting opening of the glycidyl oxirane group and adding to said lipid molecule a thiol moiety having a protective group bound thereto;

removing said protecting group to produce a thiol-substituted steroid lipid;

reacting a polyurethane with a bi-functional linker comprising a thiol-reactive group, to yield an intermediate polyurethane having a thiol-reactive functional group wherein the thiol-reactive functional group is substituted on said urethane group nitrogen; and

reacting the thiol-substituted steroid lipid with the intermediate polyurethane having a thiol-reactive functional group to yield the modified polyurethane.

6. The process of claim 5 , wherein the epihalohydrin is epibromohydrin.

7. The process of claim 5 , wherein the thiolating agent is selected from the group consisting of thiosulfate, thiourea, trityl mercaptan, tert-butyl mercaptan, thiocyanate, and thioalkanoic acids having 2-6 carbon atoms.

8. The process of claim 7 , wherein the thiolating agent is thioacetic acid.

9. The process of claim 5 , wherein the bi-functional linker is a dihaloalkane having 1-12 carbon atoms.

10. The process of claim 9 , wherein the bi-functional linker is 1,4-dibromobutane.