Antioxidant-based poly(anhydride-esters)

• US 9,862,672 B2
• Filed: 05/29/2014
• Issued: 01/09/2018
• Est. Priority Date: 05/29/2013
• Status: Active Grant

• Current Assignee: Rutgers University
• Original Assignee: Rutgers University
• Inventors: Uhrich, Kathryn, Morano, Michelle
• Primary Examiner(s): Pipic, Alma
• Application Number:
  US14/894,166
• Publication Number:
  US 20160130211A1
• Time in Patent Office: 1,321 Days
• CPC Class Codes: A61K 2800/522 Antioxidants; Radical scavengers
• CPC Class Codes: A61K 2800/56 Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
• CPC Class Codes: A61K 8/025 Explicitly spheroidal or spherical shape
• CPC Class Codes: A61K 8/11 Encapsulated compositions
• CPC Class Codes: A61K 8/37 Esters of carboxylic acids
• CPC Class Codes: A61K 8/375 the alcohol moiety containing more than one hydroxy group
• CPC Class Codes: A61K 8/85 Polyesters
• CPC Class Codes: A61Q 17/04 Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• CPC Class Codes: C07C 69/734 Ethers
• CPC Class Codes: C08G 63/06 derived from hydroxycarboxylic acids
• CPC Class Codes: C08G 63/66 Polyesters containing oxygen in the form of ether groups C08G63/42, C08G63/58 take precedence

Abstract

Certain embodiments of the invention provide antioxidant-based diacids and polymers comprising glycol groups as described herein, and methods of use thereof. In certain embodiments the polymers described herein are formulated as microspheres or hydrogels. Described herein is the chemical incorporation of antioxidants, e.g., coumaric acid, ferulic acid, and sinapic acid, into a polymer backbone for use, e.g., in applications for localized release and rapid delivery. As provided, the chemical composition of the linker molecules used (of which hold together two bioactives via ester linkages) may be used to vary the hydrophilicity of the polymer. The bioactive release rate may also be altered for a tunable release delivery system, allowing for increased bioactive release compared to other linkers previously utilized.

Claims

1. A polymer selected from:

2. The polymer of claim 1, wherein R₁ is OCH₃ and R₂ is H.

3. The polymer of claim 1, wherein R₁ is OCH₃ and R₂ is OCH₃.

4. The polymer of claim 1, wherein R₁ is H and R₂ is H.

5. A microsphere comprising the polymer as described in claim 1.

7. A pharmaceutical composition comprising the polymer as described in claim 1 and a pharmaceutically acceptable carrier.

8. A cosmetic comprising the polymer as described in claim 1.

9. A sunscreen comprising the polymer as described in claim 1.

10. A method of reducing oxidative stress in a cell of a mammal, preventing photodamage in skin of a mammal, and/or treating a disorder associated with oxidative stress in a mammal, comprising administering the polymer as described in claim 1 to the mammal.

11. The method of claim 10, wherein the polymer is administered topically.

12. A hydrogel comprising a blend comprising (a) the polymer as described in claim 1 and (b) a hydrophilic polymer.

13. The hydrogel of claim 12, wherein the hydrophilic polymer is selected from the group consisting of poly(N-vinyl-2-pyrrolidone), poly(vinyl alcohol), and poly(ethylene oxide).

14. The hydrogel of claim 13, wherein the hydrophilic polymer is poly(N-vinyl-2-pyrrolidone).

15. The hydrogel of claim 12, wherein the polymer as described in claim 1 is physically crosslinked with the hydrophilic polymer through hydrophobic interactions.

16. A method of making a hydrogel comprising blending and solvent casting (a) the polymer as described in claim 1 and (b) a hydrophilic polymer, under conditions that provide a hydrogel.

17. The method of claim 16, further comprising crosslinking (a) the polymer as described in claim 1 with (b) the hydrophilic polymer, wherein the crosslinking is by ultraviolet radiation, gamma radiation, or a crosslinking agent.

18. A method for promoting wound healing in a mammal, comprising contacting the hydrogel as described in claim 12 with a wound of the mammal.

19. A method of therapeutically treating the skin of a mammal, comprising contacting the hydrogel as described in claim 12 with the skin of the mammal.

6. A diacid selected from: