Claims for Patent: 10,159,645

Summary for Patent: 10,159,645

Title:	Combination therapy for COPD
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.
Inventor(s):	Sauro BONELLI, Francesca Usberti, Enrico Zambelli
Assignee:	Chiesi Farmaceutici SpA
Application Number:	US14/812,190
Patent Claims:	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 according to claim 1, wherein the glycopyrronium bromide is the racemic mixture (3S,2′R),(3R,2'S)-3-[(cyclopentylhydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide. 39. A composition according to claim 1, wherein the composition is free of excipients other than the ethanol, the HFA-134a, and the hydrochloric acid. 40. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 25 to a subject in need thereof. 41. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 25 to a subject in need thereof. 42. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 27 to a subject in need thereof. 43. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 27 to a subject in need thereof. 44. A method for the treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to claim 39 to a subject in need thereof. 45. A method for the treatment of asthma, comprising administering an effective amount of a pharmaceutical composition according to claim 39 to a subject in need thereof.