Pharmaceutical compositions based on novel anticholinergics and p38 kinase inhibitors

• US 20040044020A1
• Filed: 07/01/2003
• Published: 03/04/2004
• Est. Priority Date: 07/09/2002
• Status: Abandoned Application

• Current Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Pairet, Michel, Pieper, Michael P., Meade, Christopher J. M.
• Application Number:
  US10/611,717
• Publication Number:
  US 20040044020A1
• Time in Patent Office: Days
• US Class Current: 514/291
• 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 31/416 condensed with carbocyclic ring systems, e.g. indazole
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• 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]

Abstract

The present invention relates to novel pharmaceutical compositions based on novel anticholinergics and p38 kinase inhibitors, processes for preparing them and their use in the treatment of respiratory diseases.

Claims

1. ) A Pharmaceutical composition comprising one or more anticholinergics of formula A

2. ) The Pharmaceutical composition according to claim 1, wherein the active substances A and B are present either together in a single formulation or in two separate formulations.

3. ) The Pharmaceutical composition according to claim 2, wherein for A X⁻

is selected from among chloride, bromide, methansulphonate and p-toluenesulphonate.

4. ) The Pharmaceutical composition according to claim 3, characterised in that in A X⁻

denotes bromide.

5. ) The Pharmaceutical composition according to claim 4, wherein the p38 kinase inhibitor B is selected from the group of compounds disclosed in U.S. Pat. No. 5,716,972, U.S. Pat. No. 5,686,455, U.S. Pat. No. 5,656,644, U.S. Pat. No. 5,593,992, U.S. Pat. No. 5,593,991, U.S. Pat. No. 5,663,334, U.S. Pat. No. 5,670,527, U.S. Pat. No. 5,559,137, 5,658,903, U.S. Pat. No. 5,739,143, U.S. Pat. No. 5,756,499, U.S. Pat. No. 6,277,989, U.S. Pat. No. 6,340,685, and U.S. Pat. No. 5,716,955 and PCT applications WO 92/12154, WO 94/19350, WO 95/09853, WO 95/09851, WO 95/09847, WO 95/09852, WO 97/25048, WO 97/25047, WO 97/33883, WO 97/35856, WO 97/35855, WO 97/36587, WO 97/47618, WO 97/16442, WO 97/16441, WO 97/12876, WO 98/25619, WO 98/06715, WO 98/07425, WO 98/28292, WO 98/56377, WO 98/07966, WO 98/56377, WO 98/22109, WO 98/24782, WO 98/24780, WO 98/22457, WO 98/52558, WO 98/52559, WO 98/52941, WO 98/52937, WO 98/52940, WO 98/56788, WO 98/27098, WO 98/47892, WO 98/47899, WO 98/50356, WO 98/32733, WO 99/58523, WO 99/01452, WO 99/01131, WO 99/01130, WO 99/01136, WO 99/17776, WO 99/32121, WO 99/58502, WO 99/58523, WO 99/57101, WO 99/61426, WO 99/59960, WO 99/59959, WO 99/00357, WO 99/03837, WO 99/01441, WO 99/01449, WO 99/03484, WO 99/15164, WO 99/32110, WO 99/32111, WO 99/32463, WO 99/64400, WO 99/43680, WO 99/17204, WO 99/25717, WO 99/50238, WO 99/61437, WO 99/61440, WO 00/26209, WO 00/18738, WO 00/17175, WO 00/20402, WO 00/01688, WO 00/07980, WO 00/07991, WO 00/06563, WO 00/12074, WO 00/12497, WO 00/31072, WO 00/31063, WO 00/23072, WO 00/31065, WO 00/35911, WO 00/39116, WO 00/43384, WO 00/41698, WO 00/69848, WO 00/26209, WO 00/63204, WO 00/07985, WO 00/59904, WO 00/71535, WO 00/10563, WO 00/25791, WO 00/55152, WO 00/55139, WO 00/17204, WO 00/36096, WO 00/55120, WO 00/55153, WO 00/56738, WO 01/21591, WO 01/29041, WO 01/29042, WO 01/62731, WO 01/05744, WO 01/05745, WO 01/05746, WO 01/05749, WO 01/05751, WO 01/27315, WO 01/42189, WO 01/00208, WO 01/42241, WO 01/34605, WO 01/47897, WO 01/64676, WO 01/37837, WO 01/38312, WO 01/38313, WO 01/36403, WO 01/38314, WO 01/47921, WO 01/27089, DE 19842833, and JP 2000 86657.

6. ) The Pharmaceutical composition according to claim 5, wherein the p38 kinase inhibitor B is selected from the group of compounds disclosed in U.S. Pat. No. 6,277,989, U.S. Pat. No. 6,340,685, WO 00/12074, WO 00/12497, WO 00/59904, WO 00/71535, WO 01/64676, WO 99/61426, WO 00/10563, WO 00/25791, WO 01/37837, WO 01/38312, WO 01/38313, WO 01/38314, WO 01/47921, WO 99/61437, WO 99/61440, WO 00/17175, WO 00/17204, WO 00/36096, WO 98/27098, WO 99/00357, WO 99/58502, WO 99/64400, WO 99/01131, WO 00/43384, WO 00/55152, WO 00/55139, and WO 01/36403.

7. ) The Pharmaceutical composition according to claim 6, wherein the p38 kinase inhibitor B is a compound of formula 1

8. ) The Pharmaceutical composition according to claim 6, wherein the p38 kinase inhibitor B is a compound of formula 2

9. ) The Pharmaceutical composition according to claim 6, wherein the p38 kinase inhibitor B is a compound of formula 3a, 3b, 3c, or 3d

10. ) The Pharmaceutical composition according to claim 6, wherein the p38 kinase inhibitor B is a compound of formula 4

11. ) The Pharmaceutical composition according to claim 6, wherein the p38 kinase inhibitor B is a compound of formula 5

12. ) The Pharmaceutical composition according to claim 6, wherein the p38 kinase inhibitor B is a compound of formula 5a

13. ) The Pharmaceutical composition according to claim 6, wherein the p38 kinase inhibitor B is a compound of formula 6

14. ) The Pharmaceutical composition according to claim 6, wherein the p38 kinase inhibitor B is a compound of formula 7

15. ) The Pharmaceutical composition according to claim 1, wherein the weight ratios of A to B are in the range from 1:

300 to 20;

1.

16. ) The Pharmaceutical composition according to claim 1 wherein the weight ratios of A to B are in the range from 1:

200 to 10;

1.

17. ) The Pharmaceutical composition according to claim 1, wherein a single application corresponds to a dosage of the active substance combination A and B of about 100 to 10000 μ

g.

18. ) The Pharmaceutical composition according to claim 15, wherein a single application corresponds to a dosage of the active substance combination A and B of about 1000 to 9000 μ

g.

19. ) The Pharmaceutical composition according to claim 1, wherein it is present in the form of a formulation suitable for inhalation.

20. ) The Pharmaceutical composition according to claim 19, wherein it is a formulation selected from among inhalable powders, propellant-containing metering aerosols and propellant-free inhalable solutions or suspensions.

21. ) The Pharmaceutical composition according to claim 20, wherein it is an inhalable powder which contains A and B in admixture with suitable physiologically acceptable excipients selected from among the monosaccharides, disaccharides, oligo- and polysaccharides, polyalcohols, salts, or mixtures of these excipients with one another.

22. ) The Inhalable powder according to claim 21, wherein the excipient has a maximum average particle size of up to 250 μ

m, preferably between 10 and 150 μ

m.

23. ) The Pharmaceutical composition according to claim 20, wherein it is an inhalable powder which contains only the active substances A and B as its ingredients.

24. ) A Capsule, wherein the capsule contains an inhalable powder according to claim 22.

25. ) The Pharmaceutical composition according to claim 20, wherein it is a propellant-containing inhalable aerosol which contains A and B in dissolved or dispersed form.

26. ) The Pharmaceutical composition according to claim 20, wherein it is a propellant-free inhalable solution or suspension which contains water, ethanol or a mixture of water and ethanol as solvent.

27. ) A method of treating an inflammatory or obstructive disease of the respiratory tract comprising administering to a patient in need thereof a therapeutically effective amount of a composition according to claim 1.