Functionalized phenolic esters and amides and polymers therefrom

• US 7,858,077 B2
• Filed: 09/06/2005
• Issued: 12/28/2010
• Est. Priority Date: 01/28/2005
• Status: Expired due to Fees

• Current Assignee: Bezwada Biomedical, LLC
• Original Assignee: Bezwada Biomedical, LLC
• Inventors: Bezwada, Rao S.
• Primary Examiner(s): Hartley; Michael G
• Assistant Examiner(s): DICKINSON, PAUL W
• Application Number:
  US11/220,044
• Publication Number:
  US 20060173065A1
• Time in Patent Office: 1,939 Days
• Field of Search: None
• US Class Current: 424/78.08
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: C07C 69/734 Ethers
• CPC Class Codes: C07C 69/92 with etherified hydroxyl groups

Abstract

The present invention relates to a compound of the formula:
R-AR—O—Y—R′

• • Wherein R represents one or more members selected from H, alkoxy, benzyloxy, aldehyde, halogen, carboxylic acid, —NO₂, —NH₂, —NHCOCH₃, and —NH—Y—R′, which is attached directly to AR or attached through an aliphatic chain. The carboxylic acid moiety in R includes but is not limited to the following carboxylic acids: benzoic acids, cinnamic acids, ferulic acid, caffeic acid, syringic acid, salicylic acid, vanillic acid, phenylacetic acids, phenylpropionic acids, and sinapinic acid.
  • -AR—O— is a biologically active phenolic moiety comprising 1 to 6 substituted or unsubstituted aryl rings that are directly bonded to each other, fused together, or joined through a linking group.
  • Y represents a member selected from:
  • —COCH₂O— (glycolic ester moiety)
  • —COCH(CH₃)O— (lactic ester moiety)
  • —COCH₂OCH₂CH₂O— (dioxanone ester moiety)
  • —COCH₂CH₂CH₂CH₂CH₂O— (caprolactone ester moiety)
  • —CO(CH₂)_mO— where m is an integer between 2-4 and 6-24 inclusive
  • —COCH₂O(CH₂CH₂O)_n— where n is an integer between 2 and 24, inclusive; and
  • R′ is either hydrogen or a benzyl or an alkyl group, the alkyl group being either straight-chained or branched.

The resultant functionalized phenolic compounds, used singly or in combinations, and their polymers have controllable degradation profiles, releasing the active component over a desired time range. The polymers are useful for biomaterials and biomedical devices, wherein said biologically active phenolic moiety is a residue of a phenolic compound.

Claims

1. A polymer comprising a unit having the formula:

AR—

O—

Y—

R′

AR—

O—

is a biologically active phenolic moiety selected from the group consisting of isopimpinellin, isoflavones, resveratrol, and bioflavonoids substituted with a functional group selected from the group consisting of alkoxy, benzyloxy, aldehyde, halogen, carboxylic acid, —

NO₂, —

NH₂, —

NHCOCH₃, —

NH—

Y—

R′

, and a combination thereof,

Y represents a member selected from the group consisting of;

—

COCH₂O—

(glycolic ester moiety)

—

COCH(CH₃)O—

(lactic ester moiety)

—

COCH₂OCH₂CH₂O—

(dioxanone ester moiety)

—

COCH₂CH₂CH₂CH₂CH₂O—

(caprolactone ester moiety)

—

CO(CH₂)_mO—

where m is an integer between 2-4 and 6-24 inclusive,

—

COCH₂—

O—

(CH₂CH₂O)_n—

where n is an integer between 2 and 24, inclusive;

and the carbonyl end of Y is attached to the O—

of said biologically active phenolic moiety to form an ester linkage; and

R′

is either hydrogen or a benzyl or an alkyl group, the alkyl group being either straight-chained or branched.

2. The polymer of claim 1, wherein said biologically active phenolic moiety comprises an active site for polymerization selected from the group consisting of a hydroxyl group, a carboxylic acid group, and an amine group.

3. The polymer of claim 2, wherein said active site for polymerization is a hydroxyl group.

4. The polymer of claim 2, wherein said active site for polymerization is an amine group.

5. The polymer of claim 2, wherein said active site for polymerization is a carboxylic acid group.

6. A biologically active composition comprising an effective amount of at least one polymer of claim 1 and a pharmaceutically acceptable excipient, wherein said composition is in a form suitable for oral, enteral, parenteral, topical, transdermal, ocular, vitreal, rectal, nasal, pulmonary, or vaginal administration.

7. An article comprising a metal or polymeric substrate and having thereon a coating, wherein said coating comprises at least one polymer according to claim 1.

8. The article of claim 7, wherein said article is an implantable bio-medical device.

9. An implantable biomedical device comprising the polymer according to claim 1.

10. A cosmetic composition comprising an effective amount of at least one polymer of claim 1 and one or more cosmetic ingredients.

11. A pharmaceutical composition comprising an effective amount of at least one polymer of claim 1 and a pharmaceutically acceptable excipient.

12. A biodegradable chewing gum composition comprising at least one polymer of claim 1.

13. An antioxidant composition comprising an effective amount of at least one polymer of claim 1.

14. The composition comprising at least one polymer according to claim 1, which is further polymerized with at least one lactone monomer selected from the group consisting of glycolide, lactide, p-dioxanone, trimethylene carbonate and caprolactone.

15. An implantable biomedical device comprising the composition according to claim 14.

16. A biodegradable chewing gum composition comprising at least one polymer of claim 14.

17. An antioxidant composition comprising an effective amount of the polymer of claim 14.

18. The polymer of claim 1, wherein said biologically active phenolic moiety is an isoflavone or an isopimpinellin or a combination thereof.

19. The polymer according to claim 18, wherein the isoflavone is selected from the group consisting of:

biochanin A, daidzein, formononetin, genistein, glycitein, orobol, pratensein, prunetin, and santal, and glucosides or β

-glycosides thereof or a combination thereof.

20. The polymer of claim 19, wherein the isoflavone is selected from the group consisting of daidzein, equol, and gycitein or a combination thereof.

21. The polymer of claim 1, wherein said phenolic moiety is resveratrol.

22. A method for delivering a therapeutic polymer to a patient in need of antioxidant therapy comprising administering to the patient an antioxidant composition comprising an effective amount of the polymer of claim 2.