Functionalized diphenolics and absorbable polymers therefrom

• US 8,288,505 B2
• Filed: 03/25/2011
• Issued: 10/16/2012
• Est. Priority Date: 12/09/2005
• Status: Active Grant

• Current Assignee: Bezwada Biomedical, LLC
• Original Assignee: Bezwada Biomedical, LLC
• Inventors: Bezwada, Rao S
• Primary Examiner(s): Puttlitz, Karl J
• Application Number:
  US13/071,623
• Publication Number:
  US 20110223254A1
• Time in Patent Office: 571 Days
• Field of Search: None
• US Class Current: 528/328
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 5/06078 and aromatic or cycloaliphatic
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present invention relates to dephenolic compounds, an example of which is shown below, which are functionalized, and polymers formed from the same.

Polymers formed from the functionalized diphenolics 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 formed from polymerizing a functionalized diphenolic compound of formula I, II, or III:

2. The polymer of claim 1, wherein the functionalized diphenolic compound is of formula Ia, IIa, or IIIa:

3. The polymer of claim 2, wherein:

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

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

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

n is independently selected from 2, 3, and 4.

4. The polymer of claim 2, wherein:

X is independently selected from;

—

CH₂COO—

;

—

CH(CH₃)COO—

;

—

CH₂CH₂OCH₂COO—

; and

,

—

CH₂CH₂CH₂CH₂CH₂COO—

;

Y is independently selected from;

—

COCH₂O—

;

—

COCH(CH₃)O—

;

—

COCH₂OCH₂ CH₂O—

;

—

COCH₂CH₂CH₂CH₂CH₂O—

;

a, b, and c, are independently selected from 0-2, provided that a+b+c total from 2-4; and

,

d is selected from 1, 2, 3, and 4.

5. The polymer of claim 4, wherein:

R′

is independently selected from hydrogen, benzyl, and C_1-4 alkyl;

a, b, and c, are independently selected from 0-2, provided that a+b+c total from 2-3; and

,

d is selected from 1, 2, and 3.

6. The polymer of claim 5, wherein:

R′

is independently selected from hydrogen, benzyl, and CH₃;

a, b, and c, are independently selected from 0-1, provided that a+b+c total from 2-3; and

,

d is selected from 1 and 2.

7. The polymer of claim 2, wherein:

X is —

CH₂COO—

;

Y is —

COCH₂O—

;

R′

is independently selected from hydrogen, benzyl, and C_1-4 alkyl;

a, b, and c, are independently selected from 0-2, provided that a+b+c total from 2-4; and

,

d is selected from 1, 2, 3, and 4.

8. The polymer of claim 7, wherein:

R′

is independently selected from hydrogen, benzyl, and CH₃; and

,

a, b, and c, are independently selected from 0-1, provided that a+b+c total from 2-3; and

,

d is selected from 1 and 2.

9. The polymer of claim 1, wherein the polymer, further comprises:

a second functionalized diphenolic.

10. The polymer of claim 1, wherein the polymer is further polymerized with a lactone monomer.

11. The polymer of claim 10, wherein the lactone monomer is selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, and p-dioxanone.

12. An implantable medical device, comprising:

a polymer of claim 1.

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

-caprolactone, trimethylene carbonate, and p-dioxanone.

14. The implantable medical device of claim 12, wherein the device is a stent.

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

-caprolactone, trimethylene carbonate, and p-dioxanone.

16. The implantable medical device of claim 12, wherein the device is a scaffold for tissue engineer, comprising:

a porous structure for the attachment and proliferation of cells.

17. The implantable medical device of claim 16, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, and p-dioxanone.

18. A coating for a stent, comprising:

a polymer of claim 1.

19. The stent coating of claim 18, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, and p-dioxanone.

20. A drug delivery system, comprising:

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

21. The drug delivery system of claim 20, 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.

22. The drug delivery system of claim 21, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, and p-dioxanone.

23. The polymer of claim 1, wherein the second repeating unit is formed from a dicarboxylic acid.

24. The polymer of claim 1, wherein the second repeating unit is formed from a dialcohol.

25. The polymer of claim 1, wherein the second repeating unit is formed from a a diisocyanate.

26. The polymer of claim 1, wherein the second repeating unit is formed from an amino-alcohol.

27. The polymer of claim 1, wherein the second repeating unit is formed from a hydroxycarboxylic acid.

28. The polymer of claim 1, wherein the second repeating unit is formed from a diamine.