Combination of Methylxanthine Compounds and Steroids to Treat Chronic Respiratory Diseases

• US 20080318913A1
• Filed: 02/13/2006
• Published: 12/25/2008
• Est. Priority Date: 02/11/2005
• Status: Active Grant

• Current Assignee: Pulmagen Therapeutics (Inflammation) Limited (Galapagos NV)
• Original Assignee: Pulmagen Therapeutics (Inflammation) Limited (Galapagos NV)
• Inventors: Finch, Harry, Fox, Justian Craig, Fitzgerald, Mary Frances
• Granted Patent: US 8,431,553 B2
• Time in Patent Office: Days
• US Class Current: 514/171
• 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 31/52 Purines, e.g. adenine
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

There is provided the use of a methylxanthine derivative such as theophylline and a steroid in a synergistic combination for the treatment of chronic obstructive pulmonary disease, wherein the combination is administered by the inhaled route for pulmonary delivery.

Claims

1-8. -8. (canceled)

9. A methylxanthine compound and a steroid for simultaneous, simultaneous separate or sequential use in the treatment of a chronic respiratory disease selected from the group consisting of chronic obstructive pulmonary disease (COPD), cystic fibrosis, steroid resistant asthma, severe asthma and paediatric asthma, wherein the composition is adapted for administration by the inhaled route for pulmonary delivery and wherein the methylxanthine compound is administered at a dose of 0.1 to 25 mg/day.

10. A pharmaceutical composition comprising a methylxanthine compound and a steroid for use in the treatment of a chronic respiratory disease selected from the group consisting of chronic obstructive pulmonary disease (COPD), cystic fibrosis, steroid resistant asthma, severe asthma and paediatric asthma, wherein the composition is adapted for administration by the inhaled route for pulmonary delivery and wherein the methylxanthine compound is administered at a dose of 0.1 to 25 mg/day.

11. A composition according to claim 9 or claim 10, wherein the methylxanthine compound is theophylline and is provided in an amount from 0.1 and 25 mg, or from 0.05 to 13 mg, or from 0.033 to 9 mg per unit dose of the composition, said unit doses corresponding respectively to those for once per day, twice per day, or three times per day treatment.

12. A composition according to claim 10 wherein the steroid is budesonide and is provided in an amount from 200 mcg to 1600 mcg, or from 100 mcg to 800 mcg, or from 65 mcg to 525 mcg per unit dose of the composition, said unit doses corresponding respectively to those for once per day, twice per day, or three times per day treatment.

13. A composition according to claim 10 wherein the steroid is fluticasone and is provided in an amount from 44 mcg and 1000 mcg, or from 22 mcg to 500 mcg, or from 11 mcg to 335 mcg per unit dose of the composition, said unit doses corresponding respectively to those for once per day, twice per day, or three times per day treatment.

14. A composition according to claim 10 wherein the steroid is Ciclesonide and is provided in an amount from 40 mcg and 500 mcg, or from 20 mcg to 250 mcg mg, or from 14 mcg to 170 mcg per unit dose of the composition, said unit doses corresponding respectively to those for once per day, twice per day, or three times per day treatment.

15. A method for the treatment of a chronic respiratory disease selected from the group consisting of chronic obstructive pulmonary disease (COPD), cystic fibrosis, steroid resistant asthma, severe asthma and paediatric asthma, comprising administering to a human patient in need thereof a composition according claim 10.

17. A kit according to claim 16 wherein the methylxanthine compound and the steroid are provided in unit dosages according to claim 10.

16. A kit for the treatment of a chronic respiratory disease selected from the group consisting of chronic obstructive pulmonary disease (COPD), cystic fibrosis, steroid resistant asthma, severe asthma and paediatric asthma, comprising a methylxanthine compound and a steroid in unit dosage form adapted for administration by the inhaled route for pulmonary delivery and wherein the methylxanthine compound is administered at a dose of 0.1 to 25 mg/day.

18. A kit according to claim 16, said kit being in the form of an inhaler.

19. A method for the treatment of a chronic respiratory disease selected from the group consisting of chronic obstructive pulmonary disease (COPD), cystic fibrosis, steroid resistant asthma, severe asthma and paediatric asthma, comprising administering by the inhaled route for pulmonary delivery to a subject in need thereof an amount of a steroid effective to treat said pulmonary disease in the subject, the improvement comprising increasing the efficacy of the steroid by also administering theophylline to the subject by the said inhaled route, wherein theophylline is administered at a dose of 0.1 to 25 mg/day.

20. A method for the treatment of a chronic respiratory disease selected from the group consisting of chronic obstructive pulmonary disease (COPD), cystic fibrosis, steroid resistant asthma, severe asthma and paediatric asthma, comprising administration by the inhaled route for pulmonary delivery of a composition comprising a methylxanthine compound and a steroid, wherein methylxanthine compound is administered at a dose between 0.1 and 25 mg/day.

21. The method of claim 20, wherein the composition comprises one or more pharmaceutically acceptable additives, diluents and/or carriers.

22. The method of claim 20, wherein the methylxanthine compound is administered at a dose that achieves plasma levels between 1 pg/L and 1 mg/L.

23. The method of claim 20, wherein the methylxanthine compound used in the composition is selected from the group consisting of theophylline, aminophylline and oxtriphylline.

24. The method of claim 20, wherein the inhaled steroid administered is selected from the group consisting of budesonide, fluticasone and ciclesonide.

25. The method of claim 20, wherein the inhaled steroid is budesonide, and said steroid is administered at doses between 200 mcg and 1600 mcg per day.

26. The method of claim 20, wherein the inhaled steroid is fluticasone, and said steroid is administered at doses between 44 mcg and 1000 mcg per day.

27. The method of claim 20, wherein the inhaled steroid is Ciclesonide, and said steroid administered at doses between 40 mcg and 500 mcg per day.