Combination therapy for COPD

Patent metadata

Field	Value
Publication number	US-10159645-B2
Application number	US-201514812190-A
Country	US
Kind code	B2
Filing date	Jul 29, 2015
Priority date	Dec 23, 2009
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

Aerosol formulations comprising glycopyrronium bromide in combination with formoterol are useful for the prevention or treatment of chronic obstructive pulmonary disease. The formulation further comprises a HFA propellant, a co-solvent, and an amount of inorganic acid sufficient to stabilize both the glycopyrronium bromide and the formoterol components. Optionally the formulation may further comprise beclometasone dipropionate.

First claim

The invention claimed is:

1. A pharmaceutical composition for use with a pressurized metered dose inhaler, comprising:
(a) glycopyrronium bromide in an amount sufficient to deliver 5 to 26 μg per actuation;
(b) formoterol fumarate in an amount sufficient to deliver 5 to 15 μg per actuation; and
(c) beclometasone dipropionate in an amount sufficient to deliver 50 to 250 μg per actuation;
dissolved in HFA-134a and ethanol, wherein:
the composition comprises hydrochloric acid in an amount equivalent to 0.19 to 0.245 μg/μl of 1M HCl;
the composition comprises ethanol in an amount of 8 to 15% w/w of the composition; and
the composition comprises HFA-134a in an amount of 85 to 90% w/w of the composition.

2. A pharmaceutical composition according to claim 1 , comprising glycopyrronium bromide in an amount of 0.015 to 0.04% w/w of the composition.

3. A pharmaceutical composition according to claim 1 , comprising formoterol fumarate in an amount of 0.005 to 0.07% w/w of the composition.

4. A pharmaceutical composition according to claim 1 , which has been purged of oxygen.

5. An aerosol canister, comprising a pharmaceutical composition according to claim 1 .

6. A canister according to claim 5 , from which oxygen has been removed from the headspace.

7. A method of filling a canister according to claim 5 , comprising:
(a) preparing a solution of glycopyrronium bromide, formoterol fumarate, and beclometasone dipropionate, in ethanol, to which hydrochloric acid has been added in an amount equivalent to 0.19 to 0.245 μg/μl of 1M HCl;
(b) filling an aerosol canister with the solution;
(c) placing a valve onto the can and vacuum crimping; and
(d) pressure-filling the canister with HFA-134a through the valve.

8. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 1 to a subject in need thereof.

9. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 2 to a subject in need thereof.

10. A method for the prevention or treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 3 to a subject in need thereof.

11. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 4 to a subject in need thereof.

12. A pharmaceutical composition according to claim 1 , comprising formoterol fumarate in an amount sufficient to deliver 6 to 12 μg per actuation.

13. A pharmaceutical composition according to claim 1 , comprising beclometasone dipropionate in an amount sufficient to deliver about 50 μs per actuation.

14. A pharmaceutical composition according to claim 1 , further comprising water in an amount of 0.005 to 0.3% w/w of the composition.

15. A pharmaceutical composition according to claim 1 , comprising beclometasone dipropionate in an amount sufficient to deliver 100 μg per actuation.

16. A pharmaceutical composition according to claim 1 , comprising beclometasone dipropionate in an amount sufficient to deliver about 200 μg per actuation.

17. A pharmaceutical composition according to claim 1 , comprising:
formoterol fumarate in an amount sufficient to deliver about 6 μg per actuation; and
beclometasone dipropionate in an amount sufficient to deliver about 100 μg per actuation.

18. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 12 to a subject in need thereof.

19. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 13 to a subject in need thereof.

20. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 14 to a subject in need thereof.

21. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 15 to a subject in need thereof.

22. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 16 to a subject in need thereof.

23. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 17 to a subject in need thereof.

24. An aerosol canister according to claim 5 , comprising a metering valve capable of delivering a volume of about 63 μl per actuation.

25. A pharmaceutical composition according to claim 1 , wherein the ethanol is anhydrous ethanol.

26. A pharmaceutical composition according to claim 1 , comprising beclometasone dipropionate in an amount of 0.07 to 0.41% w/w of the composition.

27. A pharmaceutical composition according to claim 1 , comprising:
glycopyrronium bromide in an amount of 0.015 to 0.04% w/w of the composition;
formoterol fumarate in an amount of 0.005 to 0.07% w/w of the composition; and
beclometasone dipropionate in an amount of 0.07 to 0.41% w/w of the composition.

28. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 1 to a subject in need thereof.

29. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 12 to a subject in need thereof.

30. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 13 to a subject in need thereof.

31. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 14 to a subject in need thereof.

32. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 2 to a subject in need thereof.

33. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 3 to a subject in need thereof.

34. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 4 to a subject in need thereof.

35. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 15 to a subject in need thereof.

36. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 16 to a subject in need thereof.

37. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 17 to a subject in need thereof.

38. A composition ac

Assignees

• Chiesi Farm Spa

Inventors

• Bonelli Sauro
• Usberti Francesca
• Zambelli Enrico

Classifications

• A61P43/00

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

• A61P11/06

  Antiasthmatics · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P11/08

  Bronchodilators · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title