Pharmaceutical formulations comprising 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl) phenol

Patent metadata

Field	Value
Publication number	US-11116721-B2
Application number	US-200913148982-A
Country	US
Kind code	B2
Filing date	Feb 26, 2009
Priority date	Feb 26, 2009
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

Novel pharmaceutical formulations of a beta-2 agonist for inhaled administration via the nose or mouth, and methods of using them are provided.

First claim

The invention claimed is:

1. A pharmaceutical product consisting essentially of:
(a) a dry powder formulation consisting essentially of Compound (I), which is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxyl}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol or a pharmaceutically acceptable salt thereof, present in micronized form and in a dose selected from the group consisting of 12.5, 25, and 50 mcg, calculated as the free base, and wherein Compound (I) is in admixture with lactose and 0.6 to 2% w/w of magnesium stearate, and
(b) a dry powder formulation consisting essentially of Compound (II), which is 6α, 9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester, and lactose.

2. The pharmaceutical product according to claim 1 , wherein Compound (I) is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxyl}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol triphenylacetate.

3. The pharmaceutical product according to claim 1 wherein the magnesium stearate is present in an amount of 0.75%.

4. The pharmaceutical product according to claim 1 wherein the magnesium stearate is present in an amount of 1%.

5. The pharmaceutical product according to claim 1 wherein the magnesium stearate is present in an amount of 1.25%.

6. The pharmaceutical product according to claim 1 wherein the magnesium stearate is present in an amount of 1.5%.

7. The pharmaceutical product according to claim 1 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are presented in a form adapted for separate administration.

8. The pharmaceutical product according to claim 1 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are presented in a form adapted for sequential administration.

9. The pharmaceutical product according to claim 1 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are presented in a form adapted for simultaneous administration.

10. The pharmaceutical product according to claim 1 in a form suitable for administration by oral or nasal inhalation.

11. The pharmaceutical product according to claim 3 wherein 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxyl}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol triphenylacetate is present in a dose of 25 mcg, calculated as the free base.

12. A pharmaceutical product consisting essentially of:
(a) a dry powder formulation consisting essentially of Compound (I), which is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxyl}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol, triphenyl acetate present in micronized form and in a dose of 25 mcg, calculated as the free base, and wherein Compound (I) is in admixture with lactose and 0.75 to 1.5% w/w of magnesium stearate, and
(b) a dry powder formulation consisting essentially of Compound (II), which is 6α, 9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester present in a dose of 100 mcg and lactose.

13. The pharmaceutical product according to claim 12 wherein the magnesium stearate is present in an amount of 0.75%.

14. The pharmaceutical product according to claim 12 wherein the magnesium stearate is present in an amount of 1%.

15. The pharmaceutical product according to claim 12 wherein the magnesium stearate is present in an amount of 1.25%.

16. The pharmaceutical product according to claim 12 wherein the magnesium stearate is present in an amount of 1.5%.

17. The pharmaceutical product according to claim 12 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are presented in a form adapted for separate administration.

18. The pharmaceutical product according to claim 12 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are presented in a form adapted for sequential administration.

19. The pharmaceutical product according to claim 12 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are presented in a form adapted for simultaneous administration.

20. A pharmaceutical product consisting essentially of:
(a) a dry powder formulation consisting essentially of Compound (I), which is the 4-{(1 R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxyl}hexyl)amino]-1 -hydroxyethyl}-2-(hydroxymethyl)phenol triphenyl acetate present in micronized form and in a dose of 25 mcg calculated as the free base, and wherein Compound (I) is in admixture with lactose and 0.75 to 1.5% w/w of magnesium stearate, and
(b) a dry powder formulation consisting essentially of Compound (II), which is 6α, 9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester, present in a dose of 200 mcg and lactose.

21. The pharmaceutical product according to claim 20 wherein the magnesium stearate is present in an amount of 0.75%.

22. The pharmaceutical product according to claim 20 wherein the magnesium stearate is present in an amount of 1%.

23. The pharmaceutical product according to claim 20 wherein the magnesium stearate is present in an amount of 1.25%.

24. The pharmaceutical product according to claim 20 wherein the magnesium stearate is present in an amount of 1.5%.

25. The pharmaceutical product according to claim 20 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are presented in a form adapted for separate administration.

26. The pharmaceutical product according to claim 20 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are presented in a form adapted for sequential administration.

27. The pharmaceutical product according to claim 20 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are presented in a form adapted for simultaneous administration.

28. A method for the treatment of a respiratory disease, comprising administering to a patient in need thereof, a pharmaceutical product according to claim 1 .

29. A method according to claim 28 wherein the disease is selected from the group consisting of chronic obstructive pulmonary disease, chronic bronchitis, asthma, chronic respiratory obstruction, pulmonary fibrosis, pulmonary emphysema and allergic rhinitis.

30. A method according to claim 28 wherein the disease is asthma.

31. A method according to claim 28 wherein the disease is chronic obstructive pulmonary disease.

32. A method according to claim 28 wherein administration is via inhalation by the mouth or nose.

33. A method according to claim 28 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are administered simultaneously.

34. A method according to claim 28 wherein the pharmaceutical product is administered once per day.

35. A method for the treatment of a respiratory disease, comprising administering to a patient in need thereof, a pharmaceutical product according to claim 12 .

36. A method according to claim 35 wherein the disease i

Assignees

• Baker Darrell
• Bruce Mark
• Thomas Marian
• Glaxo Group Ltd

Inventors

• Baker Darrell
• Bruce Mark
• Thomas Marian

Classifications

• A61K45/06

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

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61K31/58

  containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• A61K31/138

  Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377) · CPC title