US2014105985A1PendingUtilityA1

Topical use of levofloxacin for reducing lung inflammation

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Assignee: MPEX PHARMACEUTICALS INCPriority: Oct 7, 2008Filed: Dec 19, 2013Published: Apr 17, 2014
Est. expiryOct 7, 2028(~2.2 yrs left)· nominal 20-yr term from priority
Inventors:Michael N. DudleyRuslan Y. TsivkovskiDavid C. GriffithOlga Rodny
A61P 7/02A61P 43/00A61P 31/04A61P 29/00A61P 35/00A61P 19/04A61K 31/536C07D 498/14A61P 11/08A61K 31/7036A61K 33/06A61P 11/00A61K 31/5383A61P 11/06A61K 47/02A61K 45/06A61K 31/538Y02A50/30
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Claims

Abstract

The present invention relates to methods and compositions for the treatment of pulmonary inflammation. In particular, methods and compositions using aerosol levofloxacin or ofloxacin to reduce pulmonary inflammation are provided.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method for treating a pulmonary inflammation in a subject comprising administering to said subject in need thereof an aerosol of a solution comprising levofloxacin or ofloxacin and a divalent or trivalent cation. 
     
     
         2 . The method of  claim 1 , wherein the pulmonary inflammation is associated with at least one disorder selected from asthma, cystic fibrosis (CF), pulmonary fibrosis, chronic bronchitis (CB), bronchiectasis, chronic granulomatous disease, sinusitis, chronic obstructive pulmonary disease (COPD), or pneumonia. 
     
     
         3 . The method of  claim 1 , wherein the solution consists essentially of levofloxacin or ofloxacin and the divalent or trivalent cation. 
     
     
         4 . The method of  claim 1 , wherein the solution comprises chloride. 
     
     
         5 . The method of  claim 1 , wherein the solution comprises no lactose. 
     
     
         6 . The method of  claim 1 , wherein the solution comprises a divalent or trivalent cation concentration from about 100 mM to about 300 mM, and a levofloxacin or ofloxacin concentration from between about 75 mg/ml to about 150 mg/ml. 
     
     
         7 . The method of  claim 1 , wherein the solution comprises a divalent or trivalent cation concentration from about 150 mM to about 250 mM, and a levofloxacin or ofloxacin concentration from between about 90 mg/ml to about 125 mg/ml. 
     
     
         8 . The method of  claim 1 , wherein the solution comprises an osmolality from about 300 mOsmol/kg to about 500 mOsmol/kg, and a pH from about 5 to about 8. 
     
     
         9 . The method of  claim 1 , wherein the solution comprises an osmolality from about 350 mOsmol/kg to about 425 mOsmol/kg, and a pH from about 5 to about 6.5. 
     
     
         10 . The method of  claim 1 , wherein the solution comprises a pH from about 5.5 to about 6.5. 
     
     
         11 . The method of  claim 1 , wherein the divalent or trivalent cation is selected from magnesium, calcium, zinc, copper, aluminum, and iron. 
     
     
         12 . The method of  claim 1 , wherein the solution comprises magnesium chloride. 
     
     
         13 . The method of  claim 1 , wherein the solution comprises a levofloxacin or ofloxacin concentration between about 90 mg/ml to about 110 mg/ml, a magnesium chloride concentration between about 175 mM to about 225 mM, a pH between about 5 to about 7; an osmolarity of between about 300 mOsmol/kg to about 500 mOsmol/kg, and lacks lactose. 
     
     
         14 . The method of  claim 1 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2 microns to about 5 microns with a geometric standard deviation less than or equal to about 2.5 microns. 
     
     
         15 . The method of  claim 1 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2.5 microns to about 4.5 microns with a geometric standard deviation less than or equal to about 1.8 microns. 
     
     
         16 . The method of  claim 1 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2.8 microns to about 4.3 microns with a geometric standard deviation less than or equal to about 2 microns. 
     
     
         17 . The method of  claim 1 , comprising producing the aerosol with a vibrating mesh nebulizer. 
     
     
         18 . The method of  claim 17 , wherein the vibrating mesh nebulizer is a PART E-FLOW® nebulizer. 
     
     
         19 . The method of  claim 1 , wherein at least about 20 mg of levofloxacin or ofloxacin is administered to the lung. 
     
     
         20 . The method of  claim 1 , wherein at least about 100 mg of levofloxacin or ofloxacin is administered to the lung. 
     
     
         21 . The method of  claim 1 , wherein at least about 125 mg of levofloxacin or ofloxacin is administered to the lung. 
     
     
         22 . The method of  claim 1 , wherein at least about 150 mg of levofloxacin or ofloxacin is administered to the lung. 
     
     
         23 . The method of  claim 1 , wherein the aerosol is administered to the lung in less than about 10 minutes. 
     
     
         24 . The method of  claim 1 , wherein the aerosol is administered to the lung in less than about 5 minutes. 
     
     
         25 . The method of  claim 1 , wherein the aerosol is administered to the lung in less than about 3 minutes. 
     
     
         26 . The method of  claim 1 , wherein the aerosol is administered to the lung in less than about 2 minutes. 
     
     
         27 . The method of  claim 1 , comprising administering the aerosol once daily. 
     
     
         28 . The method of  claim 1 , comprising administering the aerosol twice daily. 
     
     
         29 . The method of  claim 1 , further comprising co-administering an additional active agent selected from the group consisting of anti-inflammatory agent, antibiotic, bronchodilator, anticholinergic, glucocorticoid, eicosanoid inhibitor, and combinations thereof. 
     
     
         30 . The method of  claim 29 , wherein co-administering comprises inhaling the additional active agent. 
     
     
         31 . The method of  claim 29 , wherein the antibiotic is selected from the group consisting of tobramycin, aztreonam, ciprofloxacin, azithromycin, erythromycin tetracycline, quinupristin, linezolid, vancomycin, and chloramphenicol, colisitin and combinations thereof. 
     
     
         32 . The method of  claim 29 , wherein the bronchodilator is selected from the group consisting of salbutamol, levosalbuterol, terbutaline, fenoterol, terbutlaine, pirbuterol, procaterol, bitolterol, rimiterol, carbuterol, tulobuterol, reproterol, salmeterol, formoterol, arformoterol, bambuterol, clenbuterol, indacterol, theophylline, roflumilast, cilomilast, and combinations thereof. 
     
     
         33 . The method of  claim 29 , wherein the anticholinergic is selected from the group consisting of ipratropium, tiotropium, and combinations thereof. 
     
     
         34 . The method of  claim 29 , wherein the glucocorticoid is selected from the group consisting of prednisone, fluticasone, budesonide, mometasone, ciclesonide, beclomethasone, and combinations thereof. 
     
     
         35 . The method of  claim 29 , wherein the eicosanoid is selected from the group consisting of montelukast, pranlukast, zafirlukast, zileuton, ramatroban, seratrodast, and combinations thereof. 
     
     
         36 . A method for treating a pulmonary inflammation in a subject, wherein the pulmonary inflammation is induced by one or more pro-inflammatory cytokines, said method comprising administering to said subject in need thereof an aerosol of a solution comprising levofloxacin or ofloxacin and a divalent or trivalent cation to achieve a reduction in the pulmonary concentration of said cytokine by at least 10%. 
     
     
         37 . The method of  claim 36 , wherein the pulmonary concentration of said cytokine is reduced by at least 20%. 
     
     
         38 . The method of  claim 36 , wherein the pulmonary concentration of said cytokine is reduced by at least 40%. 
     
     
         39 . The method of  claim 36 , wherein the pulmonary concentration of said cytokine is reduced by at least 60%. 
     
     
         40 . The method of  claim 36 , wherein the pulmonary concentration of said cytokine is reduced by at least 80%. 
     
     
         41 . A method for treating a pulmonary inflammation in a subject comprising administering to said subject in need thereof an aerosol of a solution comprising levofloxacin or ofloxacin and a divalent or trivalent cation to achieve a reduction in the pulmonary concentration of one or more pro-inflammatory cytokines selected from IL-1β, IL-6 and IL-8, whereby the pulmonary inflammation is reduced or suppressed. 
     
     
         42 . The method of  claim 41 , wherein the cytokine comprises IL-1β. 
     
     
         43 . The method of  claim 41 , wherein the cytokine comprises IL-6. 
     
     
         44 . The method of  claim 41 , wherein the cytokine comprises IL-8. 
     
     
         45 . A method for treating a pulmonary inflammation in a subject, wherein the pulmonary inflammation is induced by one or more mediators selected from TNFα and LPS, said method comprising administering to said subject in need thereof an aerosol of a solution comprising levofloxacin or ofloxacin and a divalent or trivalent cation. 
     
     
         46 . A method for reducing the pulmonary concentration of a pro-inflammatory cytokine in a subject, said method comprising administering to said subject in need thereof an aerosol of a solution comprising levofloxacin or ofloxacin and a divalent or trivalent cation, whereby the pulmonary concentration of said cytokine is reduced. 
     
     
         47 . The method of  claim 46 , wherein the cytokine comprises IL-1β. 
     
     
         48 . The method of  claim 46 , wherein the cytokine comprises IL-6. 
     
     
         49 . The method of  claim 46 , wherein the cytokine comprises IL-8.

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