Unsymmetrical aromatic ether diacids and absorbable polymers therefrom

• US 7,671,168 B2
• Filed: 02/27/2007
• Issued: 03/02/2010
• Est. Priority Date: 10/21/2005
• Status: Active Grant

• Current Assignee: Bezwada Biomedical, LLC
• Original Assignee: Bezwada Biomedical, LLC
• Inventors: Bezwada, Rao S
• Primary Examiner(s): Truong; Duc
• Application Number:
  US11/679,191
• Publication Number:
  US 20070141113A1
• Time in Patent Office: 1,099 Days
• Field of Search: 528/272, 528/425, 424/426
• US Class Current: 528/272
• CPC Class Codes: A23L 29/288 Synthetic resins, e.g. polyvinylpyrrolidone
• CPC Class Codes: A23L 33/10 using additives addition of substantially indigestible substances A23L33/21
• CPC Class Codes: A23L 33/105 Plant extracts, their artificial duplicates or their derivatives
• CPC Class Codes: A61K 2800/522 Antioxidants; Radical scavengers
• CPC Class Codes: A61K 8/37 Esters of carboxylic acids
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 31/04 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• CPC Class Codes: C07C 205/37 the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
• CPC Class Codes: C07C 217/84 the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
• CPC Class Codes: C07C 233/18 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 233/25 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 65/21 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 65/24 polycyclic
• CPC Class Codes: C07C 69/712 the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 69/732 : of unsaturated hydroxy carboxylic acids
• CPC Class Codes: C07C 69/734 : Ethers
• CPC Class Codes: C07C 69/92 : with etherified hydroxyl groups
• CPC Class Codes: C07D 311/12 : substituted in position 3 and unsubstituted in position 7
• CPC Class Codes: C07D 311/16 : substituted in position 7
• CPC Class Codes: C07D 311/36 : not hydrogenated in the hetero ring, e.g. isoflavones
• CPC Class Codes: C07D 493/04 : Ortho-condensed systems
• CPC Class Codes: C08G 63/66 : Polyesters containing oxygen in the form of ether groups C08G63/42, C08G63/58 take precedence
• CPC Class Codes: C08G 69/40 : Polyamides containing oxygen in the form of ether groups C08G69/12, C08G69/32 take precedence
• CPC Class Codes: C08G 69/44 : Polyester-amides
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present invention relates to compounds of formula I, which are unsymmetrical aromatic ether diacids, and polymers formed from the same.
[R′—(Y)_p—O]_q—Ar—[O—(X)_r—R′]_s   I

Polymers formed from the functionalized unsymmetrical aromatic ether diacids are expected to have controllable degradation profiles, enabling them to release an active component over a desired time range. The polymers are also expected to be useful in a variety of medical applications.

Claims

1. A polymer, comprising:

an unsymmetrical aromatic ether diacid of formula I;

[R′

—

(Y)_p—

O]_q—

Ar—

[O—

(X)_r—

R′

]_s  

 

I

wherein

Ar is the aromatic portion of a diphenol;

X and Y are independently selected from;

—

CH₂COO—

;

—

CH(CH₃)COO—

;

—

CH₂CH₂OCH₂COO—

;

—

CH₂CH₂CH₂CH₂CH₂COO—

;

—

(CH₂)_yCOO—

where y is independently selected from 2-4 and 6-24; and

,

—

(CH₂CH₂O)_zCH₂COO—

where z is independently selected from 2-24;

provided that the groups represented by [R′

—

(Y)_p—

O]_q— and

—

[O—

(X)_r—

R′

]_s are different from one another;

R′

is selected from H, benzyl, and C_1-6 alkyl;

p is selected from 1, 2, 3, 4, 5, and 6;

q is selected from 1, 2, and 3.

r is selected from 1, 2, 3, 4, 5, and 6; and

,

s is selected from 1, 2, and 3.

2. A polymer of claim 1 wherein:

X and Y are independently selected from;

—

CH₂COO—

;

—

CH(CH₃)COO—

;

—

CH₂CH₂OCH₂COO—

; and

,

—

CH₂CH₂CH₂CH₂CH₂COO—

;

p is selected from 1 and 2;

q is selected from 1 and 2;

r is selected from 1 and 2; and

,

s is selected from 1 and 2.

3. A polymer of claim 1, wherein

y is independently selected from 2, 3, and 4;

z is independently selected from 2, 3, and 4;

p is selected from 1, 2, and 3;

q is selected from 1, 2, and 3;

r is selected from 1, 2, and 3; and

,

s is selected from 1, 2, and 3.

4. A polymer of claim 1, wherein the unsymmetrical aromatic ether diacid is selected from:

5. A polymer of claim 1, wherein the unsymmetrical aromatic ether diacid is reacted with a compound selected from a dicarboxylic acid, a dialcohol, an amino-alcohol, and a diamine to form a polymer selected from a polyester, a polyesteramide, a polyamide, and a polyanhydride.

6. A polymer of claim 1, wherein the polymer, further comprises:

a second unsymmetrical aromatic ether diacid.

7. A polymer of claim 1, wherein the polymer is further polymerized with a lactone monomer.

8. A polymer of claim 7, wherein the lactone monomer is selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, and p-dioxanone.

9. An implantable medical device, comprising:

a polymer of claim 1.

10. The implantable medical device of claim 9, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, and p-dioxanone.

11. The implantable medical device of claim 9, wherein the device is a stent.

12. The implantable medical device of claim 11, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, and p-dioxanone.

13. The implantable medical device of claim 9, wherein the device is a scaffold for tissue engineer, comprising:

a porous structure for the attachment and proliferation of cells.

14. The implantable medical device of claim 13, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, and p-dioxanone.

15. A coating for a stent, comprising:

a polymer of claim 1.

16. The stent coating of claim 15, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, and p-dioxanone.

17. A drug delivery system, comprising:

a polymer of claim 1 physically admixed with a biologically or pharmacologically active agent.

18. The drug delivery system of claim 17, wherein the biologically or pharmacologically active agent is physically embedded or dispersed into the polymer and the polymer is in the form of a polymeric matrix.

19. The drug delivery system of claim 17, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, and p-dioxanone.

20. A polymer blend, comprising:

two different polymers of claim 1.

21. A nutritional composition, comprising at least one polymer of claim 1.

22. The nutritional composition of claim 21, wherein the diphenolic residue in the polymer was derived from a compound that is a nutritional supplement or a food intermediary.

23. A cosmetic composition, comprising at least one polymer of claim 1 and a cosmetic ingredient.

24. A pharmaceutical composition, comprising at least one polymer of claim 1 and a pharmaceutically acceptable excipient.

25. The composition of claim 24, wherein the composition is suitable for administration via a route selected from oral, enteral, parenteral, topical, transdermal, ocular, vitreal, rectal, nasal, pulmonary, and vaginal.

26. The composition of claim 24, wherein the diphenolic residue in the polymer was derived from a cancer preventing diphenol.

27. The composition of claim 26, further comprising:

an anti-cancer agent.

28. The composition of claim 24, wherein the diphenolic residue in the polymer was derived from a diphenol with antimicrobial properties.

29. The composition of claim 28, further comprising:

an antimicrobial agent.

30. The composition of claim 24, wherein the diphenolic residue in the polymer was derived from a diphenol with anti-inflammatory properties.

31. The composition of claim 30, further comprising:

anti-inflammatory agent.

32. The composition of claim 24, wherein the diphenolic residue in the polymer was derived from a diphenol with pain-reducing properties.

33. The composition of claim 32, further comprising:

a pain reducing agent.

34. The composition of claim 24, wherein the diphenolic residue in the polymer was derived from a diphenol with antioxidant properties.

35. The composition of claim 34, further comprising:

an antioxidant agent.