TREATMENT FOR LIPODYSTROPHY

• US 20130338209A1
• Filed: 01/30/2012
• Published: 12/19/2013
• Est. Priority Date: 01/31/2011
• Status: Active Grant

• Current Assignee: Zydus Lifesciences Limited
• Original Assignee: Cadila Healthcare Limited (Zydus Lifesciences Limited)
• Inventors: Pandey, Bipin, Patel, Pankaj Ramanbhai, Gambhire, Dhiraj, Jani, Rajendrakumar Hariprasad, Sata, Kaushik, Kothari, Himanshu
• Granted Patent: US 10,017,470 B2
• Time in Patent Office: Days
• US Class Current: 514/427
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 207/33 with substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 207/333 Radicals substituted by oxygen or sulfur atoms

Abstract

The present invention provides a therapeutic compound of formula (I) and their pharmaceutically acceptable salts for the prevention and treatment of lipodystrophy caused because of HIV infection or combination therapy of HIV-1 protease inhibitors (Pis) and/or reverse transcriptase inhibitors (nRTIs) by neutralizing lipohypertrophy, lipoatrophy and metabolic abnormalities in HIV patient.

Claims

1. A method for the treatment of lipodystrophy which comprises administering a compound of formula (I)

2. The method as claimed in claim 1, wherein ‘

R’

represents thioalkyl, alkoxy or hydroxyalkyl group.

3. The method as claimed in claim 1 wherein ‘

R’

represents —

SCH₃ or —

OCH₃ group.

4. The method as claimed in claim 1 wherein M⁺ represents Mg⁺².

5. The method as claimed in claim 1 wherein the lipodystophy is HIV associated lipodystrophy.

6. The method as claimed in claim 1 wherein the HIV associated lipodystrophy causes lipohypertrophy or lipoatrophy or metabolic abnormality.

7. Use of the compound of formula (I) as claimed in claim 1 for the preparation of a medicament for the treatment of HIV associated lipodystrophy.

8. Use of the compound of formula (I) as claimed in claim 1 for the preparation of a medicament for the treatment of lipohypertrophy or lipoatrophy or metabolic abnormality.

9. Use of the compound of formula (I) as claimed in claim 1 wherein the compound is administrated in a daily dosage range selected from 1 mg to 500 mg given singly or in multiple divided dosage.

10. The daily dosage as claimed in claim 9 which is in the range of 4 mg to 250 mg given singly or in multiple divided dosage.

11. The daily dosage as claimed in claim 9 which is in the range of 4 mg to 50 mg.

12. The method of treatment or use of compound of formula (I) as claimed in claim 1 which is administrated in combination with other suitable therapeutic agent.

13. A pharmaceutical composition for the treatment of lipodystophy comprising

a) The compound of formula (I) or its salt thereof as claimed in claim 1;

b) a suitable stabilizer;

c) a suitable buffering agent;

d) optionally, with one or more pharmaceutically acceptable excipients.

14. The pharmaceutical composition as claimed in claim 13 wherein the suitable stabilizer is selected from Polacrilin potassium, Potassium chloride and Sodium stearyl fumarate.

15. The pharmaceutical composition as claimed in claim 13 wherein the suitable stabilizer is preferably selected from Sodium stearyl fumarate.

16. The pharmaceutical composition as claimed in claim 13 wherein the suitable buffering agents are selected from Sodium acetate, Ammonia solution, Ammonium carbonate, Sodium borate, Adipic Acid, Glycine, monosodium glutamate.

17. The pharmaceutical composition as claimed in claim 16 wherein the suitable buffering agent is preferably selected from Ammonia solution.

18. The method for treating HIV associated lipodystrophy in a patient in need of such treatment comprising providing to such a patient the pharmaceutical composition as claimed in claim 13.

20. Use of the pharmaceutical composition as claimed in claim 1 for the preparation of medicament for the treatment of HIV associated lipodystrophy.

21. Use of the pharmaceutical composition as claimed claim 1 for the treatment of medicament for the treatment of lipohypertrophy or lipoatrophy or metabolic abnormality

22. The pharmaceutical composition as claimed in claim 1 in combination with another suitable agent selected from an agent used to control blood glucose levels, an agent used to control lipid levels, an agent used to lower or control cholesterol, an antioxidant, an appetite suppressing agent, an anti-obesity agent a probiotic or an anti-inflammatory agent.

29. The compound as claimed in claim 1 which reduces the concentration of triglyceride, Very low density lipoprotein, Apo B level.

30. The compound as claimed in claim 1 which increases high density lipoprotein, Apo A1 level.

19. The method as claimed in claim 19 wherein the HIV associated lipodystrophy causes lipohypertrophy or lipoatrophy or metabolic abnormality.

23. The compound of formula (Ia)

24. The compound as claimed in claim 23, wherein ‘

R’

represents thioalkyl, alkoxy or hydroxyalkyl group.

25. The compound as claimed in claim 23 wherein ‘

R’

represents —

SCH₃ or —

OCH₃ group.

26. The compound as claimed in claim 23 wherein M⁺ represents Mg⁺².

27. The compound as claimed in claim 23 for the treatment lipodystrophy.

28. The compound as claimed in claim 27 wherein the lipodystrophy is HIV associated lipodystrophy.

31. A pharmaceutical composition comprising compound of formula (Ia) for the treatment of lipodystrophy.

32. The pharmaceutical composition as claimed in claim 31 wherein the lipodystrophy is HIV associated lipodystrophy.