Claims for Patent: 11,116,721

Summary for Patent: 11,116,721

Title:	Pharmaceutical formulations comprising 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl) phenol
Abstract:	Novel pharmaceutical formulations of a beta-2 agonist for inhaled administration via the nose or mouth, and methods of using them are provided.
Inventor(s):	Baker; Darrell (Middlesex, GB), Bruce; Mark (Stevenage, GB), Thomas; Marian (Ware, GB)
Assignee:	Glaxo Group Limited (Middlesex, GB)
Application Number:	13/148,982
Patent Claims:	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-hydroxye- thyl}-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 6.alpha., 9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hydroxy-16.- alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-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-hydro- xyethyl}-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-hydroxye- thyl}-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-hydroxye- thyl}-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 6.alpha., 9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hydroxy-16.- alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-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 6.alpha., 9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hydroxy-16.- alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-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 is selected from the group consisting of chronic obstructive pulmonary disease, chronic bronchitis, asthma, chronic respiratory obstruction, pulmonary fibrosis, pulmonary emphysema and allergic rhinitis. 37. A method according to claim 35 wherein the disease is asthma. 38. A method according to claim 35 wherein the disease is chronic obstructive pulmonary disease. 39. A method according to claim 35 wherein administration is via inhalation by the mouth or nose. 40. A method according to claim 35 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are administered simultaneously. 41. A method according to claim 35 wherein the pharmaceutical product is administered once per day. 42. A method for the treatment of a respiratory disease, comprising administering to a patient in need thereof, a pharmaceutical product according to claim 20. 43. A method according to claim 42 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. 44. A method according to claim 42 wherein the disease is asthma. 45. A method according to claim 42 wherein the disease is chronic obstructive pulmonary disease. 46. A method according to claim 42 wherein administration is via inhalation by the mouth or nose. 47. A method according to claim 42 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are administered simultaneously. 48. A method according to claim 42 wherein the pharmaceutical product is administered once per day. 49. A pharmaceutical product consisting of: (a) a dry powder formulation of Compound (I), which is 4-{(1 R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}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 of Compound (II), which is 6.alpha., 9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hydroxy-16.- alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester, and lactose. 50. A pharmaceutical product consisting of: (a) a dry powder formulation of Compound (I), which is 4-{(1 R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}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 of Compound (II), which is 6.alpha., 9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-h- ydroxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester present in a dose of 100 mcg and lactose. 51. A pharmaceutical product consisting of: (a) a dry powder formulation of Compound (I), which is 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxyl}hexyl)amino]-1-hydroxye- thyl}-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 of Compound (II), which is 6.alpha., 9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hydroxy-16.- alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carbothioic acid S-fluoromethyl ester, present in a dose of 200 mcg, and is in admixture with lactose. 52. A method for the treatment of a respiratory disease comprising administering to a patient in need thereof a pharmaceutical product according to claim 49. 53. A method according to claim 52 wherein the disease is asthma. 54. A method according to claim 52 wherein the disease is chronic obstructive pulmonary disease. 55. A method according to claim 52 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are administered simultaneously. 56. A method according to claim 52 wherein the pharmaceutical product is administered once per day. 57. A method for the treatment of a respiratory disease comprising administering to a patient in need thereof a pharmaceutical product according to claim 50. 58. A method according to claim 57 wherein the disease is asthma. 59. A method according to claim 57 wherein the disease is chronic obstructive pulmonary disease. 60. A method according to claim 57 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are administered simultaneously. 61. A method according to claim 57 wherein the pharmaceutical product is administered once per day. 62. A method for the treatment of a respiratory disease, comprising administering to a patient in need thereof, a pharmaceutical product according to claim 51. 63. A method according to claim 62 wherein the disease is asthma. 64. A method according to claim 62 wherein the disease is chronic obstructive pulmonary disease. 65. A method according to claim 62 wherein the dry powder formulation of Compound (I) and the dry powder formulation of Compound (II) are administered simultaneously. 66. A method according to claim 62 wherein the pharmaceutical product is administered once per day. 67. The method according to claim 28 wherein Compound (I) and Compound (II) are administered in admixture with each other.