# US 8,772,437 B2 · Biodegradable nitric oxide generating polymers and related biomedical devices

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,772,437 B2
- Document ID: US8772437B2
- Status: Granted
- Kind: B2
- Application number: 14/062,464
- Filed: 2013-10-24
- Published: 2014-02-27
- Granted: 2014-07-08
- Earliest claimed: 2008-09-19
- Assignees: Northwestern University
- Applicants: Northwestern University
- Inventors: Guillermo Ameer; Melina Kibbe; Haichao Zhao
- Web page: https://patentgrep.com/patent/US8772437B2

## CPC

- A61L 31/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)}
- A61L 27/34: Macromolecular materials
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 29/085: {Macromolecular materials}
- A61L 29/16: Biologically active materials, e.g. therapeutic substances {(A61L29/048 takes precedence)}
- A61L 31/10: Macromolecular materials
- A61L 31/148: {Materials at least partially resorbable by the body}
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- C08G 63/6856: {Dicarboxylic acids and dihydroxy compounds}
- C08G 73/02: Polyamines
- C08G 73/0206: {Polyalkylene(poly)amines}
- C09D 179/02: Polyamines
- A61L 2300/114: Nitric oxide, i.e. NO
- A61L 2300/416: Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
- A61L 2300/42: Anti-thrombotic agents, anticoagulants, anti-platelet agents
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C09D: COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR (cosmetics A61K; processes for applying liquids or other fluent materials to surfaces, in general, B05D; staining wood B27K5/02; glazes or vitreous enamels C03C; natural resins, French polish, drying-oils, driers, turpentine, per se, C09F; polishing compositions other than French polish, ski waxes C09G; adhesives or use of materials as adhesives C09J; materials for sealing or packing joints or covers C09K3/10; materials for stopping leaks C09K3/12; processes for the electrolytic or electrophoretic production of coatings C25D)

## Abstract

Disclosed herein is a biodegradable nitric oxide-generating polymer comprising a nitric oxide-releasing N2O231 (NONOate) functional group. The polymer can be applied to various medical devices for the treatment of various diseases such as thrombosis and restenosis.

## Claims

### Claim 1

A biocompatible elastomeric polymer comprising polyesters of citric acid and aliphatic diol, wherein said polyesters are crosslinked by a secondary-amine-containing crosslinker.

### Claim 2 (depends on 1)

The method of claim 1 wherein the aliphatic diol is 1,8-octanediol.

### Claim 3 (depends on 1)

The polymer of claim 1 wherein the crosslinker is trans-4-hydroxy-L-proline.

### Claim 4 (depends on 3)

The polymer of claim 3 wherein the aliphatic diol is 1,8-octanediol.

### Claim 5

A method of preparing a crosslinked elastomer of a citric acid aliphatic diol pre-polymer comprising:
a) synthesizing a prepolymer of citric acid and aliphatic diol;
b) post-polymerizing the prepolymer with a crosslinker comprising a secondary amine group to form a post polymer, wherein the secondary amine group does not participate in the post-polymerization reaction.

### Claim 6 (depends on 5)

The method of claim 5 wherein the crosslinker is trans-4-hydroxy-L-proline.

### Claim 7 (depends on 6)

The method of claim 6 wherein the aliphatic diol is 1,8-octanediol.

### Claim 8

A method of preparing a biocompatible elastomeric polymer of the formula:
wherein R is hydrogen or a polymer, each A is independently selected from a NONOate-containing amine diol unit and an aliphatic diol unit, and n is an integer greater than 1, provided that at least one each of NONOate-containing amine diol unit and an aliphatic diol unit is present, comprising:
a) polycondensing a citric acid, an aliphatic diol and an amino diol;
b) crosslinking; and
c) treating the crosslinked polymer with NO gas.

### Claim 9 (depends on 8)

The method of claim 8 wherein the aliphatic diol is 1,8-octanediol.

### Claim 10 (depends on 9)

The method of claim 9 wherein the amine diol is N,N -bis(2-hydroxyethyl-ethylenediamine.

### Claim 11

A biomedical device wherein at least one surface of the device has deposited thereon a coating comprising a NO-releasing elastomer selected from:
a) a compound having formula:
Wherein R is hydrogen or a polymer, each A is independently selected from a NONOate-containing amine diol unit and an aliphatic diol unit, and n is an integer greater than 1, provided that at least one each of NONOate-containing amine diol unit and an aliphatic diol unit is present; and
b)an elastomeric polymer comprising polyesters of citric acid and aliphatic diol crosslinked by a secondary-amine containing crosslinker.

### Claim 12 (depends on 11)

The biomedical device of claim 11 wherein A selected from —O—(CH2) 8—O—and —O—(CH2)2—N[(N+═N—O−)O−]—(CH2)2—N+H2—(CH2)2—O—.

### Claim 13 (depends on 11)

The biomedical device of claim 11 wherein the crosslinker is trans-4-hydroxy-L-proline.

### Claim 14 (depends on 13)

The biomedical device of claim 13 wherein the aliphatic diol is1,8-octanediol.

### Claim 15 (depends on 12)

The biomedical device of claim 12 wherein the device is an implantable device.

### Claim 16 (depends on 14)

The biomedical device of claim 14 wherein the device is an implantable device.

### Claim 17 (depends on 5)

The method of claim 5, further comprising:
c) reacting the post-polymer with NO gas.

### Claim 18 (depends on 1)

A device comprising the biocompatible elastomeric polymer of claim 1.