TREATMENT OF DEGENERATIVE JOINT DISEASE

• US 20140256642A1
• Filed: 10/10/2012
• Published: 09/11/2014
• Est. Priority Date: 10/10/2011
• Status: Active Grant

• Current Assignee: Ampio Pharmaceuticals, Inc.
• Original Assignee: Ampio Pharmaceuticals, Inc.
• Inventors: Bar-Or, David, Winkler, James V.
• Granted Patent: US 8,980,834 B2
• Time in Patent Office: Days
• US Class Current: 514/16.8
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis

Abstract

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP.

Claims

1. A method of treating a degenerative joint disease comprising administering to an animal in need thereof an effective amount of a pharmaceutical composition comprising DA-DKP.

2. The method of claim 1, wherein the degenerative joint disease is osteoarthritis.

3. The method of claim 1 wherein the composition is administered no more frequently than once every six months, once every 5 months, once every 4 months, once every 3 months, or once every 2 months.

4. The method of claim 1, wherein the composition is administered by an administration route selected from the group consisting of local administration, topical administration, and injection.

5. The method of claim 4, wherein administration by injection is by intra-articular injection.

6. The method of claim 5, wherein the composition administered by intra-articular injection is a composition having a concentration of DA-DKP from about 50 μ

M to about 350 μ

M.

7. The method of claim 1, wherein the composition further comprises N-acetyl-tryptophan (NAT), caprylic acid, caprylate or combinations thereof.

8. The method of claim 7, wherein the composition is a composition having a concentration of NAT, caprylic acid, caprylate or combinations thereof from about 4 mM to about 20 mM.

9. The method of claim 1, wherein the DA-DKP is in a composition prepared by removing albumin from a solution of a human serum albumin composition.

10. The method of claim 9, wherein the step of removing the albumin comprises treating the human serum albumin composition by a separation method selected from the group consisting of ultrafiltration, sucrose gradient centrifugation, chromatography, salt precipitation, and sonication.

11. The method of claim 10, wherein the step of removing comprises passing the human serum albumin composition over an ultrafiltration membrane with a molecular weight cut off that retains the albumin, and wherein the resulting filtrate comprises DA-DKP.

12. The method of claim 11, wherein the ultrafiltration membrane has a molecular weight cutoff of less than 50 kDa, less than 40 kDa, less than 30 kDa, less than 20 kDa, less than 10 kDa, less than 5 kDa or less than 3 kDa.

13. The method of claim 9, wherein the composition further comprises NAT, caprylic acid, caprylate or combinations thereof.

14. The method of claim 13, wherein the composition is a composition having a concentration of NAT, caprylic acid, caprylate or combinations thereof from about 4 mM to about 20 mM.

15. The method of claim 1, wherein the pharmaceutical composition further comprises a second drug selected from the group consisting of an analgesic, an anti-inflammatory drug, and combinations thereof.

16. A pharmaceutical product comprising a DA-DKP-containing composition formulated for administration by injection.

17. The pharmaceutical product of claim 16, wherein the product is formulated for administration by intra-articular injection.

18. The pharmaceutical product of claim 16, wherein the DA-DKP is prepared by removing albumin from a solution of a human serum albumin composition.

19. The pharmaceutical product of claim 18, wherein the step of removing the albumin comprises treating the human serum albumin composition by a separation method selected from the group consisting of ultrafiltration, sucrose gradient centrifugation, chromatography, salt precipitation, and sonication.

20. The pharmaceutical product of claim 19, wherein the step of removing comprises passing the human serum albumin composition over an ultrafiltration membrane with a molecular weight cut off that retains the albumin, and wherein the resulting filtrate comprises DA-DKP.

21. The pharmaceutical product of claim 20, wherein the ultrafiltration membrane has a molecular weight cutoff of less than 50 kDa, less than 40 kDa, less than 30 kDa, less than 20 kDa, less than 10 kDa, less than 5 kDa or less than 3 kDa.

22. The pharmaceutical product of claim 17, wherein the DA-DKP administered by intra-articular injection is a composition having a concentration of DA-DKP from about 50 μ

M to about 350 μ

M.

23. The pharmaceutical product claim 16, wherein the DA-DKP composition further comprises NAT, caprylic acid, caprylate and combinations thereof.

24. The pharmaceutical product of claim 23, wherein the composition is a composition having a concentration of NAT, caprylic acid, caprylate or combinations thereof from about 4 mM to about 20 mM.

25. The pharmaceutical product of claim 16, further comprising a pharmaceutically-acceptable carrier.

26. A kit comprising a pharmaceutical product comprising a DA-DKP-containing composition formulated for administration by injection.

27. The kit of claim 26, wherein the DA-DKP is prepared by removing albumin from a solution of a human serum albumin composition.