Medicament compositions comprising a heterocyclic compound and an anticholinergic

• US 20060286040A1
• Filed: 08/05/2004
• Published: 12/21/2006
• Est. Priority Date: 08/06/2003
• Status: Abandoned Application

• Current Assignee: Kyowa Hakko Kogyo Company Limited (Kirin Holdings Company Limited)
• Original Assignee: Kyowa Hakko Kogyo Company Limited (Kirin Holdings Company Limited)
• Inventors: Meade, Christopher J. Montague, Abe, Yuzuru, Pairet, Michel, Pieper, Michael P., Miki, Ichiro
• Application Number:
  US10/567,127
• Publication Number:
  US 20060286040A1
• Time in Patent Office: Days
• US Class Current: 424/46
• CPC Class Codes: A61K 31/357 having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to novel pharmaceutical compositions based on anticholinergics of the formula 1; wherein X⁻, R¹ ? and Ar are defined as in claim 1, and a heterocyclic compound of the formula 2. Furthermore, the invention relates to processes for preparing them and their use in the treatment of respiratory complaints.

Claims

1. A pharmaceutical composition, comprising

(a) an anticholinergic of the formula 1

wherein

X⁻

represents a chlorine, bromine, iodine, methanesulphonate or trifluoromethanesulphonate anion;

R¹ represents hydroxy or methyl;

Ar represents phenyl or thienyl or a pharmacologically acceptable acid addition salt, solvate or hydrate thereof;

(b) a compound of the formula 2

or a pharmacologically acceptable acid addition salt solvate, or hydrate thereof; and

(c) optionally, a pharmaceutically acceptable excipient.

2. The pharmaceutical composition according to claim 1, wherein the anticholinergic of the formula 1 is a compound of the formula 1a

wherein

X⁻

represents a chlorine, bromine, iodine, methanesulphonate or trifluoromethanesulphonate anion.

or a pharmacologically acceptable acid addition salt, solvate, or hydrate thereof

3. The pharmaceutical composition according to claim 2, wherein X represents bromine.

4. The pharmaceutical composition according to claim 1, wherein the anticholinergic of the formula 1 is a compound of the formula 1b

wherein

X⁻

represents a chlorine, bromine, iodine, methanesulphonate or trifluoromethanesulphonate anion.

or a pharmacologically acceptable acid addition salt, solvate, or hydrate thereof.

5. The pharmaceutical composition according to claim 4, characterised in that X represents bromine.

6. The pharmaceutical composition according to claim 1, wherein the anticholinergic of the formula 1 and the compound of the formula 2 are present either together in a single formulation or in two separate formulations.

7. The pharmaceutical composition according to claim 1, wherein the weight ratios of the anticholinergic of the formula 1 to the compound of the formula 2 are in the range from 1:

4000 to 8;

1.

8. The pharmaceutical composition according to claim 2, wherein the weight ratios of the compound of the formula 1a to the compound of the formula 2 are in the range from 1:

4000 to 1;

2.5.

9. The pharmaceutical composition according to claim 4, wherein the weight ratios of the compound of the formula 1b to the compound of the formula 2 are in the range from 1:

4000 to 8;

1.

10. The pharmaceutical composition according to claim 1, wherein the total dosage per single dose of the combination of the anticholinergic of the formula 1 and the compound of the formula 2 is from 25 to 10000 μ

g.

11. The pharmaceutical composition according to claim 1, wherein the composition is in the form of a formulation suitable for inhalation.

12. The pharmaceutical composition according to claim 11, wherein the composition is a formulation selected from among inhalable powders, propellant-containing metering aerosols and propellant-free inhalable solutions or suspensions.

13. The pharmaceutical composition according to claim 12, wherein the composition is an inhalable powder which contains the anticholinergic of the formula 1 and the compound of the formula 2 in admixture with physiologically acceptable excipients including monosaccharides, disaccharides, oligo- and polysaccharides, cyclodextrines, polyalcohols, salts, or mixtures thereof.

14. The Inhalable powder according to claim 13, wherein the excipient has a maximum average particle size of up to 250 μ

m.

15. The pharmaceutical composition according to claim 12, wherein the composition is an inhalable powder which contains only the anticholinergic of the formula 1 and the compound of the formula 2 as its ingredients.

16. The pharmaceutical composition according to claim 12, wherein the composition is a propellant-containing inhalable aerosol which contains the anticholinergic of the formula 1 and the compound of the formula 2 in dissolved or dispersed form.

17. The pharmaceutical composition in the form of a propellant-containing inhalable aerosol according to claim 16, wherein the propellant is a, hydrocarbons or a halohydrocarbon.

18. The pharmaceutical composition in the form of a propellant-containing inhalable aerosol according to claim 17, wherein the propellant gas is TG11, TG12, TG134a (1,1,1,2-tetrafluoroethane), TG227 (1,1,1,2,3,3,3-heptafluoropropane) or a mixture thereof.

19. The pharmaceutical composition according to claim 12, wherein the composition is a propellant-free inhalable solution or suspension which contains water, ethanol or a mixture of water and ethanol as solvent.

20. The pharmaceutical composition in the form of an inhalable solution or suspension according to claim 19, wherein the pH is 2 to 5.

21. A capsule comprising an inhalable powder according to claim 13.

25. A method of prophylaxis of, treating of, or reducing the exacerbations associated with pulmonary diseases comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition according to claim 1 either in a single combined form, separately, or separately and sequentially where the sequential administration is close in time, or remote in time.

26. The method according to claim 25 wherein the pulmonary disease is asthma, COPD, or another obstructive airways disease exacerbated by bronchial hyperreactivity and bronchospasm.

27. The method according to claim 25 wherein said administration by inhalation comprises simultaneous or sequential delivery of said combination of therapeutic agents, comprising the anticholinergic of the formula 1 and the compound of the formula 2, in the form of an aerosol or dry powder dispersion.

28. The method according to claim 25, wherein the anticholinergic of the formula 1 is the compound of the formula 1a.

29. The method according to claim 25, wherein the anticholinergic of the formula 1 is the compound of the formula 1b.

30. A package comprising a pharmaceutical composition according to claim 1 for insertion into a device of simultaneous or sequential delivery of said pharmaceutical composition in the form of an aerosol or dry powder dispersion, to a mammal in need of thereof.

31. An Inhaler comprising a pharmaceutical composition according to claim 1 for simultaneous or sequential delivery of said pharmaceutical composition in the form of an aerosol or dry powder dispersion, to a mammal in need thereof.

22-24. -24. (canceled)

32. A Pharmaceutical composition, comprising an anticholinergic in combination with the compound of the formula 2 optionally in the form of a pharmacologically acceptable acid addition salt thereof, optionally in the form of a solvate or hydrate and optionally together with a pharmaceutically acceptable excipient.

33-37. -37. (canceled)