Pharmaceutical compositions

Patent metadata

Field	Value
Publication number	US-9795619-B2
Application number	US-201314651673-A
Country	US
Kind code	B2
Filing date	Dec 14, 2013
Priority date	Dec 14, 2012
Publication date	Oct 24, 2017
Grant date	Oct 24, 2017

Abstract

The present invention relates to long acting pharmaceutical compositions of betulin derivatives or pharmaceutically acceptable salts thereof, useful in the treatment or prevention of Human Immunodeficiency Virus (HIV) infections.

First claim

The invention claimed is:

1. A long acting parenteral pharmaceutical composition, comprising: a compound of Table 1 or a pharmaceutically acceptable salt thereof.

2. A long acting parenteral pharmaceutical composition, comprising: the compound of Formula I

or a pharmaceutically acceptable salt thereof.

3. A method for the treatment of an HIV infection in a human having an HIV infection, comprising: administering to the human a long acting parenteral pharmaceutical composition according to either claim 1 or 2 .

4. A method for the treatment of an HIV infection in a human having an HIV infection, comprising: administering to the human a long acting parenteral pharmaceutical composition including the compound of Formula I

or a pharmaceutically acceptable salt thereof.

5. The pharmaceutical composition according to claim 2 , further comprising a surfactant system.

6. The pharmaceutical composition according to claim 5 , wherein the surfactant system comprises a surfactant in an amount ranging from about 0.1% (w/v) to about 3% (w/v) surfactant.

7. The pharmaceutical composition according to claim 5 , wherein the surfactant system comprises a surfactant in an amount ranging from about 0.2% (w/v) to about 0.4% (w/v) surfactant.

8. The pharmaceutical composition according to claim 5 , wherein the surfactant system comprises about 0.4% (w/v) surfactant.

9. The pharmaceutical composition according to claim 5 , wherein the surfactant system comprises a surfactant selected from the group consisting of polyoxyethylene sorbitan fatty acid esters, poloxamers, sorbitan esters of fatty acids (SPAN), polyethoxylated castor oil, tocopheryl polyethylene glycol succinate, and polyvinyl alcohols.

10. The pharmaceutical composition according to claim 9 , wherein the surfactant system comprises a surfactant that is polysorbate 80.

11. The pharmaceutical composition according to claim 5 , wherein the surfactant system comprises a stabilizer that is selected from the group consisting of polyethylene glycols, carboxymethylcellulose calcium, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxymethylpropylcellulose, polysaccharides, hyarluronic acid, polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP).

12. The pharmaceutical composition according to claim 11 , wherein the surfactant system comprises a stabilizer that is polyethylene glycol.

13. The pharmaceutical composition according to claim 12 , wherein the surfactant system comprises a stabilizer that is PEG-3350.

14. The pharmaceutical composition according to claim 11 , wherein the surfactant system comprises a stabilizer in an amount that ranges from about 1% (w/v) to about 5% (w/v) stabilizer.

15. The pharmaceutical composition according to claim 14 , wherein the surfactant system comprises about 2% (w/v) stabilizer.

16. The pharmaceutical composition according to claim 5 , wherein the surfactant system comprises a buffer salt.

17. The pharmaceutical composition according to claim 16 , wherein the surfactant system comprises a buffer salt that is phosphate buffered saline.

18. The pharmaceutical composition according to claim 16 , wherein the surfactant system comprises a buffer salt at a concentration of about 10 mM.

19. The pharmaceutical composition according to claim 2 , wherein the compound of Formula I is in a crystalline form prior to encapsulating into a microparticle and combining with a surfactant system.

20. The pharmaceutical composition according to claim 2 , wherein the compound of Formula I is in an amorphous microparticle form.

21. The pharmaceutical composition according to claim 2 , wherein the compound of Formula I is in a microparticle form, wherein the microparticles of the compound of Formula I range in size from about 0.05 μm to about 100 μm.

22. The pharmaceutical composition according to claim 2 , wherein the compound of Formula I is in a microparticle form, wherein the microparticles of the compound of Formula I range in size from about 0.1 μm to about 5 μm.

23. The pharmaceutical composition according to claim 2 , wherein the compound of Formula I is encapsulated in a polymer.

24. The pharmaceutical composition according to claim 22 , wherein the compound of Formula I is encapsulated in a polymer that comprises poly (lactic-co-glycolic) acid.

25. The method according to claim 4 , wherein the human is administered the long acting parenteral pharmaceutical composition including the compound of Formula I, on a dosing regimen ranging from about every week to about every three months.

26. The method according to claim 25 , wherein the human is administered the long acting parenteral pharmaceutical composition including the compound of Formula I, on a dosing regimen ranging from about every week to about every two months.

27. The method according to claim 25 , wherein the human is administered the long acting parenteral pharmaceutical composition including the compound of Formula I, on a dosing regimen that is monthly.

28. A long acting parenteral pharmaceutical composition, comprising: the compound of Formula I

or a pharmaceutically acceptable salt thereof,
in combination with one or more additional compounds selected from the group consisting of dolutegravir, ritonavir, rilpivirine, and a compound having the following structure:

or a pharmaceutically salt thereof.

29. A method for the treatment of an HIV infection in a human having an HIV infection, comprising: administering to the human a long acting parenteral pharmaceutical composition including the compound of Formula I

or a pharmaceutically acceptable salt thereof,
in combination with one or more additional compounds selected from the group consisting of dolutegravir, ritonavir, rilpivirine, and a compound having the following structure:

30. The pharmaceutical composition according to claim 2 , wherein the compound of Formula I is in a microparticle form, wherein the microparticles of the compound of Formula I range in size from about 0.05 μm to about 100 μm, wherein said microparticles comprise substantially the same size.

31. The pharmaceutical composition according to claim 2 , wherein the compound of Formula I is in a microparticle form, wherein the microparticles of the compound of Formula I range in size from about 0.05 μm to about 100 μm, wherein said microparticles comprise two or more substantially different particle sizes that provide for earlier and later release after administration to a subject and result in varying absorption kinetics therein.

32. The pharmaceutical composition according to claim 2 , wherein the compound of Formula I is in a mic

Assignees

• Glaxosmithkline Llc

Inventors

• Cai Shenshen
• Johns Brian Alvin
• Spaltenstein Andrew

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/18

  for HIV · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/575 Primary

  substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol · CPC title

• C07J63/008

  Expansion of ring D by one atom, e.g. D homo steroids · CPC title