Polyanhydrides with therapeutically useful degradation products

• US 7,534,852 B2
• Filed: 09/06/2006
• Issued: 05/19/2009
• Est. Priority Date: 09/10/1997
• Status: Expired due to Fees

• Current Assignee: Rutgers University
• Original Assignee: Rutgers University
• Inventors: Uhrich, Kathryn E.
• Primary Examiner(s): Boykin; Terressa M
• Application Number:
  US11/516,464
• Publication Number:
  US 20070213500A1
• Time in Patent Office: 986 Days
• Field of Search: 424/78.17, 424/486, 424/59, 424/78.27, 424/78.37, 424/327.4, 528/206, 528/310, 525/437, 525/438
• US Class Current: 528/206
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• 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: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: C08G 67/04 Polyanhydrides
• CPC Class Codes: C08L 73/02 Polyanhydrides

Abstract

An aromatic polyanhydride comprising a repeating unit having the structure

is disclosed, wherein Ar and R are selected so that the aromatic polyanhydride hydrolyzes to form a therapeutic salicylate, another non-steroidal anti-inflammatory, an antifibrotic aminobenzoate, or a vasoconstricting phenylethanolamine. Implantable medical devices, such as scaffolding implants for tissue reconstruction, drug delivery systems prepared from the aromatic polyanhydrides, as well as therapeutic dosage forms and treatment methods are also disclosed.

Claims

1. An aromatic polyanhydride comprising a repeating unit having the structure:

2. A drug delivery system comprising the aromatic polyanhydride of claim 1 physically admixed with a biologically or pharmaceutically active agent.

3. A drug delivery system comprising a biologically or pharmaceutically active agent physically embedded or dispersed into a polymeric matrix formed from the aromatic polyanhydride of claim 1.

4. A drug delivery system comprising a biologically or pharmaceutically active agent covalently bonded to the aromatic polyanhydride of claim 1.

5. An implantable medical device comprising the aromatic polyanhydride of claim 1.

6. The implantable medical device of claim 5, wherein said device is a scaffolding implant for tissue reconstruction.

7. A method for site-specific or systemic drug delivery comprising implanting in the body of a patient in need thereof an implantable drug delivery device comprising a therapeutically effective amount of the aromatic polyanhydride of claim 1.

8. A method for treating inflammation comprising administering to a patient in need thereof an effective amount of the aromatic polyanhydride of claim 1.

9. The method of claim 8, wherein the aromatic polyanhydride is administered orally.

10. The method of claim 8, wherein the inflammation is digestive inflammation.

11. The method of claim 8, wherein the inflammation is caused by a digestive disorder.

12. The method of claim 11, wherein the digestive disorder is a bowel disorder.

13. The method of claim 11, wherein the digestive disorder is an inflammatory bowel disease.

14. The method of claim 11, wherein the digestive disorder is Crohn'"'"'s disease.

15. A dosage form comprising an effective amount of the aromatic polyanhydride of claim 1 and a pharmaceutically acceptable excipient.

16. The dosage form of claim 15 that is an oral dosage form.

17. The aromatic polyanhydride of claim 1, wherein each Z₁ is a difunctional moiety selected from the group consisting of esters, and carbamates.

18. The aromatic polyanhydride of claim 1, wherein R₁ is selected from the group consisting of (—

CH₂—

CH₂—

O—

)_m, (—

CH₂—

CH₂—

CH₂—

O—

)_m, and (—

CH₂—

CHCH₃—

O—

)_m, wherein m is selected so that R₁ has between 2 and 20 carbon atoms, inclusive.

19. The aromatic polyanhydride of claim 1, wherein R₁ is (—

CH₂—

)_n, wherein n is from 1 to 20, inclusive.

20. The aromatic polyanhydride of claim 1, wherein each Z₁ is an ester.

21. The aromatic polyanhydride of claim 19, wherein each Z₁ is an ester.

22. The aromatic polyanhydride of claim 20, wherein n is 6.

23. The aromatic polyanhydride of claim 21, wherein n is 6.

24. The aromatic polyanhydride of claim 20, wherein n is 8.

25. The aromatic polyanhydride of claim 21, wherein n is 8.