Method for treating cystic fibrosis

• US 8,168,597 B2
• Filed: 10/21/2009
• Issued: 05/01/2012
• Est. Priority Date: 10/22/2008
• Status: Active Grant

• Current Assignee: Merck Sharp & Dohme LLC (Merck & Co., Inc.)
• Original Assignee: Inspire Pharmaceuticals Incorporated (Akorn Holdings Topco LLC)
• Inventors: Kellerman, Donald J., Krishnamoorthy, Ramesh, Boyer, José L., Schaberg, Amy E.
• Primary Examiner(s): Crane, Lawrence E
• Application Number:
  US12/603,506
• Publication Number:
  US 20100099635A1
• Time in Patent Office: 923 Days
• Field of Search: None
• US Class Current: 514/28
• 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 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention is directed to a method for treating cystic fibrosis. The method comprises the steps of: identifying a patient suffering from cystic fibrosis, and administering to the patient an effective amount of denufosol or a pharmaceutically acceptable salt thereof and an effective amount of a macrolide. In one method, denufosol and the macrolide are administered by inhalation, preferably in a single formulation. In another method, denufosol is administered by inhalation and the macrolide is administered orally. The present invention is also directed to a pharmaceutical formulation comprising denufosol or a pharmaceutically acceptable salt thereof, a macrolide, and a pharmaceutically acceptable carrier. Preferred denufosol is denufosol tetrasodium and preferred macrolide is azithromycin. The pharmaceutical formulation preferably is in a form of an inhalable dry powder or in a liquid form.

Claims

1. A method for treating cystic fibrosis, comprising the steps of:

identifying a patient suffering from cystic fibrosis,

administering to the patient an effective amount of denufosol or a pharmaceutically acceptable salt thereof and an effective amount of a macrolide.

2. The method according to claim 1, wherein the denufosol is administered by inhalation.

3. The method according to claim 2, wherein the macrolide is administered by oral administration or inhalation.

4. The method according to claim 1, wherein said denufosol is denufosol tetrasodium.

5. The method according to claim 1, wherein said denufosol and the macrolide are co-administered.

6. The method according to claim 1, wherein said denufosol and the macrolide are co-administered in a single pharmaceutical formulation by inhalation.

7. The method according to claim 1, wherein said macrolide is selected from the group consisting of azithromycin, clarithromycin, dirithromycin, erythromycin, and roxithromycin.

8. The method according to claim 7, wherein said macrolide is azithromycin.

9. The method according to claim 1, wherein the effective amount of denufosol is about 100-400 mg per day and an effective amount of a macrolide is 10-200 mg per day.

10. A pharmaceutical formulation comprising denufosol or a pharmaceutically acceptable salt thereof, a macrolide, and a pharmaceutically acceptable carrier.

11. The pharmaceutical formulation according to claim 10, wherein said denufosol is denufosol tetrasodium and said macrolide is azithromycin.

12. The pharmaceutical formulation according to claim 10, which is in a form of an inhalable dry powder.

13. The pharmaceutical formulation according to claim 12, comprising about 30-130 mg of denufosol tetrasodium and about 3-70 mg of azithromycin in a unit dosage form.

14. The pharmaceutical formulation according to claim 10, which is in a liquid form.

15. The pharmaceutical formulation according to claim 14, comprising about 5-50 mg/mL of denufosol tetrasodium and about 0.5-8 mg/mL of azithromycin.