You're using a free limited version of DrugPatentWatch: Upgrade for Complete Access

Last Updated: December 22, 2024

Claims for Patent: 11,090,294


✉ Email this page to a colleague

« Back to Dashboard


Summary for Patent: 11,090,294
Title:Combinations of a muscarinic receptor antagonist and a beta-2 adrenoreceptor agonist
Abstract: Combinations of a muscarinic acetylcholine receptor antagonist and a beta 2 agonist for inhaled administration via the nose or mouth, and methods of using them are provided.
Inventor(s): Baker; Darrell (Uxbridge, GB), Bruce; Mark (Stevenage, GB), Crater; Glenn (Mississauga, CA), Noga; Brian (Durham, NC), Thomas; Marian (Ware, GB), Wire; Patrick (Durham, NC)
Assignee: Glaxo Group Limited (Middlesex, GB)
Application Number:15/678,246
Patent Claims: 1. A method of treating chronic obstructive pulmonary disease in a human comprising: the once per day administration to the human of a pharmaceutical combination product, comprising: a) a compound of the formula: ##STR00007## wherein X.sup.- is a pharmaceutically acceptable anion, wherein Compound (I) is in an amount of about 62.5 mcg/dose in the combination product, and is in the form of a dry powder; and b) 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol, or a pharmaceutically acceptable salt thereof (Compound (II)), wherein Compound (II) is in an amount of about 25 mcg/dosein the combination product, and is in the form of a dry powder; wherein Compounds (I) and (II) are presented in a form adapted for simultaneous administration.

2. The method according to claim 1, wherein for Compound (I) the pharmaceutically acceptable anion is selected from the group consisting of chloride, bromide, iodide, hydroxide, sulfate, nitrate, phosphate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate or p-toluenesulfonate.

3. The method according to claim 2, wherein Compound (I) is 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicycl- o[2.2.2] octane bromide.

4. The method according to claim 1, wherein Compound (II) is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol triphenylacetate.

5. The method according to claim 3, wherein Compound (II) is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol triphenylacetate.

6. The method according to claim 1, wherein the pharmaceutical product is in a form suitable for administration by inhalation via a medicament dispenser, wherein said medicametn dispenser is selected from the group consisting of a reservoir dry powder inhaler, a unit-dose dry powder inhaler, and a pre-metered multi-dose dry powder inhaler.

7. The method according to claim 6, wherein Compound (I) and Compound (II) are presented in (i) separate dry powder compositions or (ii) an admixed dry powder composition.

8. The method according to claim 7, wherein each separate dry powder composition or the admixed dry powder composition contains a carrier, which is lactose.

9. The method according to claim 8, wherein each seperate or the admixed composition contains a ternary agent.

10. The method according to claim 9, wherein the ternary agent is magnesium stearate.

11. The method according to claim 7, wherein said separate or admixed composition is in unit dose form, and further wherein the unit dose form is selected from the group consisting of a capsule, a cartridge and a blister.

12. The method according to claim 1, wherein the pharmaceutical combination product further comprises 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hy- droxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester (fluticasone furoate).

13. The method according to claim 12, wherein the 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hy- droxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester (fluticasone furoate) is present in an amount of about 100 mcg/dose.

14. The method according to claim 5, wherein the pharmaceutical combination product further comprises 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hy- droxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester (fluticasone furoate).

15. The method according to claim 14, wherein the 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hy- droxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester (fluticasone furoate) is present in an amount of about 100 mcg/dose.

16. The method according to claim 5, wherein the pharmaceutical product is in a form suitable for administration by inhalation via a medicament dispenser, wherein said medicament dispenser is selected from the group consisting of a reservoir dry powder inhaler, a unit-dose dry powder inhaler, and a pre-metered multi-dose dry powder inhaler.

17. The method according to claim 16, wherein Compound (I) and Compound (II) are presented in (i) separate dry powder compositions or (ii) an admixed dry powder composition.

18. The method according to claim 17, wherein each separate dry powder composition or the admixed dry powder composition contains a carrier, which is lactose.

19. The method according to claim 18, wherein each seperate or the admixed composition contains a ternary agent.

20. The method according to claim 19, wherein the ternary agent is magnesium stearate.

21. The method according to claim 17, wherein said separate or admixed composition is in unit dose form, and further wherein the unit dose form is selected from the group consisting of a capsule, a cartridge and a blister.

22. A method of treating chronic obstructive pulmonary disease (COPD) in a human comprising: simultaneously administering, via inhalation, to said human, once per day, a pharmaceutical combination product comprising: a) a first dry powder composition comprising: (i) about 62.5 mcg/dose of a compound of the formula: ##STR00008## wherein X.sup.- is a pharmaceutically acceptable anion; (ii) lactose; and (iii) magnesium stearate in an amount of about 0.6% w/w of said first dry powder composition; and b) a second dry powder composition comprising: (i) about 25 mcg/dose of 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol, or a pharmaceutically acceptable salt thereof (Compound (II)); (ii) lactose; and (iii) magnesium stearate in an amount of about 1.0% w/w of said second dry powder composition.

23. The method according to claim 22, wherein for Compound (I), the pharmaceutically acceptable anion is selected from the group consisting of chloride, bromide, iodide, hydroxide, sulfate, nitrate, phosphate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate or p-toluenesulfonate.

24. The method according to claim 23, wherein for Compound (I) the pharmaceutically acceptable anion is bromide.

25. The method according to claim 22, wherein Compound (II) is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol triphenylacetate.

26. The method according to claim 24, wherein Compound (II) is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol triphenylacetate.

27. The method according to claim 22, wherein pharmaceutical combination product further comprises 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hy- droxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester (fluticasone furoate) present in an amount of about 100 mcg/dose.

28. The method according to claim 23, wherein pharmaceutical combination product further comprises 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hy- droxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester (fluticasone furoate) present in an amount of about 100 mcg/dose.

29. The method according to claim 24, wherein pharmaceutical combination product further comprises 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hy- droxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester (fluticasone furoate) present in an amount of about 100 mcg/dose.

30. The method according to claim 25, wherein pharmaceutical combination product further comprises 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hy- droxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester (fluticasone furoate) present in an amount of about 100 mcg/dose.

31. A method of treating chronic obstructive pulmonary disease (COPD) in a human comprising: simultaneously administering, via inhalation, to said human, once per day, a pharmaceutical combination product comprising: a) a first dry powder composition comprising: (i) about 62.5 mcg/dose of a compound of the formula: ##STR00009## wherein X.sup.- is a pharmaceutically acceptable anion; (ii) about 25 mcg/dose 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol, or a pharmaceutically acceptable salt thereof (Compound (II)); (iii) carrier excipient; and (iv) a ternary agent, and (b) a second dry powder composition comprising: (i) 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hy- droxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester (fluticasone furoate), present in an amount of about 100 mcg/dose; and (ii) carrier excipient.

32. The method according to claim 31, wherein for Compound (I), the pharmaceutically acceptable anion is selected from the group consisting of chloride, bromide, iodide, hydroxide, sulfate, nitrate, phosphate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate or p-toluenesulfonate.

33. The method according to claim 32, wherein for Compound (I) the pharmaceutically acceptable anion is bromide.

34. The method according to claim 31, wherein Compound (II) is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol triphenylacetate.

35. The method according to claim 33, wherein Compound (II) is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol triphenylacetate.

36. The method of claim 31, wherein the carrier excipient comprises lactose, and the ternary agent comprises magnesium stearate.

37. The method of claim 36, wherein the pharmaceutical combination product is administered via a medicament dispenser, wherein said medicament dispenser is selected from the group consisting of a reservoir dry powder inhaler, a unit-dose dry powder inhaler, and a pre-metered multi-dose dry powder inhaler.

38. The method according to claim 37, wherein each of said first and second dry powder compositions is in unit dose form, wherein said unit dose forms are independently selected from the group consisting of a capsule, a cartridge and a blister.

39. The method of claim 35, wherein the carrier excipient comprises lactose, and the ternary agent comprises magnesium stearate.

40. The method of claim 39, wherein the pharmaceutical combination product is administered via a medicament dispenser, wherein said medicament dispenser is selected from the group consisting of a reservoir dry powder inhaler, a unit-dose dry powder inhaler, and a pre-metered multi-dose dry powder inhaler.

41. The method according to claim 40, wherein each of said first and second dry powder compositions are in unit dose form, wherein said unit dose forms are indepenently selected from the group consisting of a capsule, a cartridge and a blister.

42. The method according to claim 10, wherein the ternary agent is magnesium stearate, present in an amount of about 0.6% w/w of a composition of Compound (I).

43. The method according to claim 10, wherein the ternary agent is magnesium stearate, present in an amount of about 1.0% w/w of a composition of Compound (II).

44. The method according to claim 10, wherein the ternary agent is magnesium stearate, present in an amount of about 0.6% w/w of a composition of Compound (I) and in an amount of about 1.0%w/w of a composition of Compound (II).

45. The method according to claim 20, wherein the ternary agent is magnesium stearate, present in an amount of about 0.6% w/w of a composition of Compound (I).

46. The method according to claim 20, wherein the ternary agent is magnesium stearate, present in an amount of about 1.0% w/w of a composition of Compound (II).

47. The method according to claim 20, wherein the ternary agent is magnesium stearate, present in an amount of about 0.6% w/w of a composition of Compound (I) and in an amount of about 1.0% w/w of a composition of Compound (II).

48. The method according to claim 20, wherein the pharmaceutical combination product further comprises 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hy- droxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester (fluticasone furoate).

49. The method according to claim 48, wherein the fluticasone furoate is present in an amount of about 100 mcg/dose.

50. The method of claim 48, wherein the pharmaceutical combination product is administered via a medicament dispenser, wherein said medicament dispenser is selected from the group consisting of a reservoir dry powder inhaler, a unit-dose dry powder inhaler, and a pre-metered multi-dose dry powder inhaler.

51. The method according to claim 50, wherein Compound (I) and Compound (II) are presented in (i) separate dry powder compositions or (ii) an admixed dry powder composition.

52. The method according to claim 51, wherein each separate dry powder composition or the admixed dry powder composition contains a carrier, which is lactose.

53. The method according to claim 52, wherein each separate or the admixed composition contains a ternary agent.

54. The method according to claim 53, wherein the ternary agent is magnesium stearate.

55. The method according to claim 54, wherein the magnesium stearate is present in a composition comprising Compound (II), in an amount of about 1.0% w/w of the composition comprising Compound (II).

56. The method according to claim 49, wherein said dry powder compositions are in unit dose form, wherein each of said unit dose forms are independently selected from the group consisting of a capsule, a cartridge or a blister.

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.