Aerosol fluoroquinolone formulations for improved pharmacokinetics

• US 10,149,854 B2
• Filed: 06/28/2017
• Issued: 12/11/2018
• Est. Priority Date: 10/07/2008
• Status: Active Grant

• Current Assignee: Horizon Orphan, LLC (Amgen Inc.)
• Original Assignee: Horizon Orphan, LLC (Amgen Inc.)
• Inventors: Griffith, David C., Dudley, Michael N., Surber, Mark W., Bostian, Keith A., Rodny, Olga
• Primary Examiner(s): Rao, Savitha M
• Application Number:
  US15/635,818
• Publication Number:
  US 20180104252A1
• Time in Patent Office: 531 Days
• CPC Class Codes: A61K 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/536 ortho- or peri-condensed with carbocyclic ring systems
• CPC Class Codes: A61K 31/538 ortho- or peri-condensed with carbocyclic ring systems
• CPC Class Codes: A61K 31/5383 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• 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: 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to the field of antimicrobial agents. In particular, the present invention relates to the use of aerosolized fluoroquinolones formulated with divalent or trivalent cations and having improved pulmonary availability for the treatment and management of bacterial infections of the lung and upper respiratory tract.

Claims

1. An aqueous pharmaceutical solution comprising about 100 mg/ml of levofloxacin and about 200 mM of magnesium chloride.

2. The solution of claim 1 having a pH from about 5 to about 7 and an osmolality from about 300 mOsmol/kg to about 500 mOsmol/kg.

3. The solution of claim 1, comprising a dose of about 240 mg of the levofloxacin.

20. A nebulizer comprising the aqueous pharmaceutical solution of claim 1.

4. An aqueous pharmaceutical solution comprising about 90 mg/ml to about 110 mg/ml of levofloxacin and about 190 mM to about 210 mM of a magnesium cation.

5. The solution of claim 4, wherein the magnesium cation is in the form of magnesium chloride.

6. The solution of claim 4, wherein the magnesium cation is in the form of magnesium sulfate.

7. The solution of claim 4 having a pH from about 5 to about 7 and an osmolality from about 300 mOsmol/kg to about 500 mOsmol/kg.

8. The solution of claim 4 having a pH from about 6.0 to about 6.5 and an osmolality from about 350 mOsmol/kg to about 400 mOsmol/kg.

9. The solution of claim 4, comprising a dose of about 240 mg levofloxacin.

10. An aqueous pharmaceutical solution comprising about 80 mg/ml to about 120 mg/ml of levofloxacin and about 160 mM to about 240 mM of a cation, wherein the cation is magnesium, calcium, zinc, copper, aluminum, or iron.

11. The solution of claim 10, comprising about 175 mM to about 225 mM of the cation.

12. The solution of claim 10, comprising about 90 mg/ml to about 110 mg/ml of the levofloxacin and about 190 mM to about 210 mM of the cation.

13. The solution of claim 10, comprising about 100 mg/ml of levofloxacin and about 200 mM of the cation.

14. The solution of claim 10, wherein the cation is magnesium.

15. The solution of claim 14, wherein the cation is in the form of magnesium chloride.

16. The solution of claim 10 having a pH from about 5 to about 7 and an osmolality from about 300 mOsmol/kg to about 500 mOsmol/kg.

17. The solution of claim 16 having a pH from about 6.0 to about 6.5 and an osmolality from about 350 mOsmol/kg to about 400 mOsmol/kg.

18. The solution of claim 10, comprising a dose of about 180 mg to about 300 mg of the levofloxacin.

19. The solution of claim 18, comprising a dose of about 240 mg of the levofloxacin.