Kojic acid polymers

• US 10,543,162 B2
• Filed: 04/11/2016
• Issued: 01/28/2020
• Est. Priority Date: 04/10/2015
• Status: Active Grant

• Current Assignee: Rutgers University
• Original Assignee: Rutgers University
• Inventors: Uhrich, Kathryn, Smith, Kervin, Faig, Jonathan
• Primary Examiner(s): Song, Jianfeng
• Application Number:
  US15/565,313
• Publication Number:
  US 20180116945A1
• Time in Patent Office: 1,387 Days
• CPC Class Codes: A61K 31/351 not condensed with another ring
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61K 8/498 having 6-membered rings or their condensed derivatives, e.g. coumarin
• CPC Class Codes: A61K 8/85 Polyesters
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61Q 19/02 for chemically bleaching or whitening the skin
• CPC Class Codes: C08G 64/06 not containing aliphatic unsaturation

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.

Claims

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

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

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 —

(CH₂OCH₂)₃—

.

4. A method for preparing a polymer as described in claim 2:

comprising polymerizing a corresponding diol of formula 4;

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.

12. The polymer of claim 3, wherein R is —

(CH₂OCH₂)₃—

.

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 C₁-C₆ alkyl.

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

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

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 —

(CH₂OCH₂)₃—

.

8. The polymer of claim 5 wherein R³ is a divalent hydrocarbon chain having 4 carbon atoms.

11. A method for preparing a polymer as described in claim 6:

comprising reacting a corresponding diol of formula 4;

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.

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 C₁-C₆ alkyl.