Kojic acid polymers

Patent metadata

Field	Value
Publication number	US-10543162-B2
Application number	US-201615565313-A
Country	US
Kind code	B2
Filing date	Apr 11, 2016
Priority date	Apr 10, 2015
Publication date	Jan 28, 2020
Grant date	Jan 28, 2020

Abstract

A controlled release system for kojic acid having improved stability has been identified. To minimize degradation, kojic acid was incorporated into a hydrolytically degradable polymer (e.g., a polycarbonate-ester)). By synthesizing polymer precursors containing kojic acid-linker-kojic acid chemical structures, versatile monomers were developed that can be used to modulate polymer properties. Additionally the synthetic method lends itself to the development of other polymer systems. Polymers having one or more groups that will yield kojic acid upon degradation of the polymer backbone, as well as methods of use thereof are described.

First claim

What is claimed is:

1. A polymer having a backbone that comprises one or more units of formula (I):

wherein:
R is a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain, having from 1 to 25 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (—O—) or (—NR a —), wherein the chain is optionally substituted on carbon with one or more substituents selected from the group consisting of (C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkylthio, azido, cyano, nitro, halo, hydroxy, oxo, carboxy, aryl, aryloxy, heteroaryl, and heteroaryloxy, and wherein R a is H or C 1 -C 6 alkyl.

2. The polymer of claim 1 , which has a backbone that comprises formula 5:

wherein:
R is a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain, having from 1 to 25 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (—O—) or (—NR a —), wherein the chain is optionally substituted on carbon with one or more substituents selected from the group consisting of (C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkylthio, azido, cyano, nitro, halo, hydroxy, oxo, carboxy, aryl, aryloxy, heteroaryl, and heteroaryloxy;
R a is H or C 1 -C 6 alkyl; and
n is an integer from 2 to 500 inclusive.

3. The polymer of claim 1 , wherein R is a divalent hydrocarbon chain having 2, 4, 7 or 8 carbon atoms or wherein R is —(CH 2 OCH 2 ) 3 —.

4. A method for preparing a polymer as described in claim 2 :
comprising polymerizing a corresponding diol of formula 4:

to provide the polymer.

5. A polymer having a backbone that comprises one or more units of formula (II):

wherein:
R and R 3 are each independently a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain, having from 1 to 25 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (—O—) or (—NR a —), wherein the chain is optionally substituted on carbon with one or more substituents selected from the group consisting of (C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkylthio, azido, cyano, nitro, halo, hydroxy, oxo, carboxy, aryl, aryloxy, heteroaryl, and heteroaryloxy, and R a is H or C 1 -C 6 alkyl.

6. The polymer of claim 5 , which has a backbone that comprises formula 6:

wherein:
R and R 3 are each independently a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain, having from 1 to 25 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (—O—) or (—NR a —), wherein the chain is optionally substituted on carbon with one or more substituents selected from the group consisting of (C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkylthio, azido, cyano, nitro, halo, hydroxy, oxo, carboxy, aryl, aryloxy, heteroaryl, and heteroaryloxy;
R a is H or C 1 -C 6 alkyl; and
n is an integer from 2 to 500 inclusive.

7. The polymer of claim 5 wherein R is a divalent hydrocarbon chain having 2, 4, 7 or 8 carbon atoms or wherein R is —(CH 2 OCH 2 ) 3 —.

8. The polymer of claim 5 wherein R 3 is a divalent hydrocarbon chain having 4 carbon atoms.

9. A composition comprising a polymer as described in claim 1 and a pharmaceutically acceptable carrier.

10. A cosmetic formulation comprising a polymer as described in claim 1 and an acceptable carrier.

11. A method for preparing a polymer as described in claim 6 :
comprising reacting a corresponding diol of formula 4:

with a corresponding diacid chloride of formula:

to provide the polymer.

12. The polymer of claim 3 , wherein R is —(CH 2 OCH 2 ) 3 —.

13. A composition comprising a polymer as described in claim 5 and a pharmaceutically acceptable carrier.

14. A cosmetic formulation comprising a polymer as described in claim 5 and an acceptable carrier.

15. The polymer of claim 1 , wherein R is a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain, having from 3 to 15 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (—O—) or (—NR a —), and wherein R a is H or C 1 -C 6 alkyl.

16. The polymer of claim 5 , wherein R is a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain, having from 3 to 15 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (—O—) or (—NR a —), and wherein R a is H or C 1 -C 6 alkyl.

Assignees

• Univ Rutgers

Inventors

• Uhrich Kathryn
• Smith Kervin
• Faig Jonathan

Classifications

• A61K8/498

  having 6-membered rings or their condensed derivatives, e.g. coumarin · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61K8/85 Primary

  Polyesters · CPC title

• A61K47/593

  Polyesters, e.g. PLGA or polylactide-co-glycolide · CPC title

• A61K31/351

  not condensed with another ring · CPC title