ORGANIC COMPOUNDS

• US 20100166671A1
• Filed: 08/29/2007
• Published: 07/01/2010
• Est. Priority Date: 08/31/2006
• Status: Abandoned Application

• Current Assignee: Barbara Haeberlin, Stephen P. Collingwood
• Original Assignee: Barbara Haeberlin, Stephen P. Collingwood
• Inventors: Haeberlin, Barbara, Collingwood, Stephen P.
• Application Number:
  US12/377,630
• Publication Number:
  US 20100166671A1
• Time in Patent Office: Days
• US Class Current: 424/43
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Medicaments comprising (A) an antimuscarinic agent, (B) a beta-2 adrenoreceptor agonist and (C) a corticosteroid for the treatment of inflammatory or obstructive airways diseases.

Claims

1. A medicament comprising, separately or together

(A) a glycopyrronium salt;

(R)-3-(2-Hydroxy-2,2-diphenyl-acetoxy)-1-(isoxazol-3-ylcarbamoyl-methyl)-1-azonia-bicyclo-[2.2.2]octane bromide or ((R)-3-((R)-2-cyclohexyl-2-hydroxy-2-phenylacetoxy)-1-(isoxazol-3-ylcarbamoylmethyl)-1-azoniabicyclo[2.2.2]octane;

(B) a beta-2 adrenoceptor agonist selected from salmeterol and formoterol, or pharmaceutically acceptable salts thereof; and

(C) corticosteroid selected from fluticasone propionate, 4-Methyl-thiazole-5-carboxylic acid (6S,9R,10S,11S,13S,16R,17R)-6,9-difluoro-17 fluoromethylsulfanylcarbonyl-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl ester, Furan-2-carboxylic acid (6S,9R,10S,11S,13S,16R,17R)-6,9-difluoro-17-fluoromethylsulfanylcarbonyl-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl ester, and budesonide; and

3-methyl-thiophene-2-carboxylic acid (6S,9R,10S,11S,13S,16R,17R)-9-chloro-6-fluoro-11-hydroxy-17-methoxycarbonyl-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta-a]phenanthren-17-yl ester;

for simultaneous, sequential or separate administration in the treatment of an inflammatory or obstructive airways disease.

7. A medicament according to claim 1 wherein (C) is mometasone furoate.

11. A medicament according to claim 7 wherein said compound of formula II is 3-methyl-thiophene-2-carboxylic acid (6S,9R,10S,11S,13S,16R,17R)-9-chloro-6-fluoro-11-hydroxy-17-methoxycarbonyl-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta-[a]phenanthren-17-yl ester.

12. A medicament according to claim 1, which is a pharmaceutical composition comprising a mixture of effective amounts of (A), (B) and (C) optionally together with at least one pharmaceutically acceptable carrier.

14. A medicament according to claim 31, in which (A) is (R)-3-(2-Hydroxy-2,2-diphenyl-acetoxy)-1-(isoxazol-3-ylcarbamoyl-methyl)-1-azonia-bicyclo-[2.2.2]octane bromide.

15. A medicament according to claim 31 wherein the glycopyrronium salt is a racemate or a mixture of diastereomers.

16. A medicament according to claim 15 wherein the glycopyrronium salt is a single enantiomer.

17. A medicament according to claim 16 wherein the glycopyrronium salt is glycopyrronium bromide.

18. A medicament according to claim 17 wherein the glycopyrronium salt is (3S,2′

R)-3-[(cyclopentyl-hydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide or (3R,2′

R)-3-[(cyclopentyl-hydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide.

19. A medicament according to claim 17 wherein the glycopyrronium salt is (3S,2′

R/3R,2′

S)-3-[(cyclopentyl-hydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide.

20. medicament according to claim 1, which is in inhalable form and is

(i) an aerosol comprising a mixture of (A), (B) and (C) in solution or dispersion in a propellant;

(ii) a combination of an aerosol containing (A) in solution or dispersion in a propellant, with an aerosol containing (B) in solution or dispersion in a propellant and an aerosol containing (C) in solution or dispersion in a propellant;

(iii) a nebulizable composition comprising a dispersion of (A), (B) and (C) in an aqueous, organic or aqueous/organic medium;

or

(iv) a combination of a dispersion of (A) in an aqueous, organic or aqueous/organic medium with a dispersion of (B) in an aqueous, organic or aqueous/organic medium and a dispersion of (C) in an aqueous, organic or aqueous/organic medium.

24. A method of treating an inflammatory or obstructive airways disease in a subject in need of such treatment, which comprises administering to said subject a medicament of claim 1 containing (A), (B) and (C) in effective amounts.

25. A method of treating chronic obstructive pulmonary disease in a subject in need of such treatment, which comprises administering to said subject a medicament of claim 1 containing (A), (B) and (C) in effective amounts.

26. A pharmaceutical kit comprising (A), (B) and (C) as defined in claim 1 in separate unit dosage forms, said forms being suitable for administration of (A), (B) and (C) in effective amounts, together with one or more inhalation devices for administration of (A), (B) and (C).

31. A medicament according to claim 1 wherein (A) is a glycopyrronium salt.

32. A medicament according to claim 1, in which (A) is (R)-3-((R)-2-cyclohexyl-2-hydroxy-2-phenylacetoxy)-1-(isoxazol-3-ylcarbamoylmethyl)-1-azoniabicyclo[2.2.2]octane.

2-6. -6. (canceled)

8-10. -10. (canceled)

13. (canceled)

21. A medicament according to claim 1, in which (A), (B) and (C) are present in inhalable form as a dry powder comprising finely divided (A), (B) and (C) optionally together with at least one particulate pharmaceutically acceptable carrier.

21-23. -23. (canceled)

27-30. -30. (canceled)