Roflumilast and glycopyrronium combination

• US 20070167496A1
• Filed: 02/25/2005
• Published: 07/19/2007
• Est. Priority Date: 02/27/2004
• Status: Abandoned Application

• Current Assignee: Nycomed GmbH (Takeda Pharmaceutical Company Limited)
• Original Assignee: Altana Pharma AG (Takeda Pharmaceutical Company Limited)
• Inventors: Karl, Christoph, Roscher, Rene
• Application Number:
  US10/589,865
• Publication Number:
  US 20070167496A1
• Time in Patent Office: Days
• US Class Current: 514/345
• 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 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The invention relates to pharmaceutical formulations containing combinations of roflumilast and a pharmaceutically acceptable salt of glycopyrronium and the use of such pharmaceutical compositions in medicine, in particular in the prophylaxis and treatment of respiratory disease.

Claims

1. A pharmaceutical formulation comprising a pharmaceutical acceptable salt of glycopyrronium, a solvate or physiologically functional derivative thereof in combination with an active pharmaceutical ingredient being a compound selected from the group consisting of roflumilast, pharmaceutically acceptable salts of roflumilast, solvates of roflumilast and physiologically functional derivatives thereof;

and a pharmaceutically acceptable carrier and/or one or more excipients.

2. The formulation according to claim 1, wherein the pharmaceutical acceptable salt of glycopyrronium and roflumilast are contained in the same pharmaceutical formulation (fixed combination).

3. The formulation according to claim 1, wherein the pharmaceutical acceptable salt of glycopyrronium and roflumilast are contained in different pharmaceutical formulations (free combination).

4. The formulation according to claim 1, comprising a compound selected from the group consisting of N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-difluoromethoxybenzamide, 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid-4-yl 1-oxide)benzamide, salts thereof and solvates thereof.

5. The formulation according to claim 1, wherein the pharmaceutical acceptable salt of glycopyrronium is selected from the group consisting of racemic forms [S,S—

, S,R—

, R,S— and

R,R-forms] of the pharmaceutical acceptable salt of glycopyrronium in any mixing ratio and enantiomerically enriched S,S—

, S,R—

, R,S— and

R,R-forms of the pharmaceutical acceptable salt of glycopyrronium.

6. The formulation according to claim 5, wherein the enantiomerically enriched form of the pharmaceutical acceptable salt of glycopyrronium is the R,R-form (i.e. (3R,2′

R)-3-[(cyclopentylhydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium).

7. The formulation according to claim 6, wherein the R,R-form has an enantiomeric purity of 90% minimum enantiomeric excess.

8. The formulation according to claim 1 wherein the pharmaceutical acceptable salt of glycopyrronium is (3R,2′

R)-3-[(cyclopentylhydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide, which substantially does not contain glycopyrronium in the S,S—

, S,R— and

/or R,S—

forms.

9. The formulation according to claim 1, comprising pharmaceutical acceptable salt of glycopyrronium and roflumilast in an amount and ratio to be effective for a twice or once daily treatment of a clinical condition in a mammal, for which a PDE 4 inhibitor and/or an anticholinergic agent is indicated.

10. The formulation according to claim 1, which is suitable for administration by inhalation.

11. The formulation according to claim 1, which is suitable for nasal administration.

12. The formulation according to claim 1, wherein roflumilast is present in a form for oral administration and the pharmaceutical acceptable salt of glycopyrronium is present in a form suitable for administration by inhalation.

13. The formulation according to claim 1, which is a dry powder and the carrier is a saccharide.

14. The formulation according to claim 13, wherein the carrier is lactose monohydrate.

20. A dry powder inhalation product comprising a pharmaceutical composition according to claim 13.

15. A method of treatment of a clinical condition in a mammal, for which a PDE 4 inhibitor and/or an anticholinergic agent is indicated, which comprises administration of a therapeutically effective amount of a pharmaceutical formulation comprising roflumilast or a pharmaceutical acceptable salt, solvate, or physiologically functional derivative thereof in combination with a pharmaceutical acceptable salt of glycopyrronium, a solvate, or physiologically functional derivative thereof, and a pharmaceutical acceptable carrier and/or one or more excipients.

16. The method according to claim 15, wherein the clinical condition is selected from the group consisting of asthma, nocturnal asthma, exercise-induced asthma, chronic obstructive pulmonary diseases (COPD), chronic bronchitis, wheezy bronchitis, emphysema, respiratory tract infection, upper respiratory tract disease, rhinitis, allergic rhinitis and seasonal rhinitis.

17. The method according to claim 16, which comprises a twice daily dosage regimen.

18. The method according to claim 16, which comprises a once daily dosage regimen.

19. The method according to claim 16, which comprises administration of a combination of a pharmaceutical acceptable salt of glycopyrronium and roflumilast in the same administration form by inhalation from an inhaler and wherein each actuation provides a dose therapeutically effective for a twice daily dosing regiment or for a once daily dosing regiment.