Aerosolized anti-infectives, anti-inflammatories, and decongestants for the treatment of sinusitis

Abstract

Pharmaceutical compositions are described that comprise one or more active ingredients selected from the group consisting of anti-infective, anti-inflammatory and mucolytic agents, and particularly to compositions formulated as a solution in a unit dose for aerosol administration to treat chronic sinusitis.

What is claimed is:  
     
         1 . A method of treating a patient suspected or diagnosed as having chronic sinusitis, comprising nasally administering an aerosolized/atomized composition comprising an agent for treatment of sinusitus, wherein the composition has a surface tension that results in penetration or adhesion of the agent in the sinuses.  
     
     
         2 . The method of  claim 1 , wherein the surface tension is about 10 to about 70 dynes/cm.  
     
     
         3 . The method of  claim 1 , wherein the composition comprises a surfactant.  
     
     
         4 . The method of  claim 1 , wherein the agent is an anti-infective, an anti-inflammatory or a mucolytic agent.  
     
     
         5 . The method of  claim 1 , wherein the composition is administered via a nebulizer.  
     
     
         6 . The method of  claim 1 , wherein the agent is selected from the group consisting of anti-infective, anti-inflammatory and mucolytic agents; 
 the surface tension of the composition is between about 10 to about 70 dynes/cm; and    the composition is formulated as a solution in a unit dose for aerosol administration to the nasal sinuses by aerosolization using a nebulizer that delivers aerosol particles of between about 1 to about 5 μm in average diameter.    
     
     
         7 . The method of  claim 1 , herein the composition is packaged with directions for its use in the treatment of sinusitis.  
     
     
         8 . The method of  claim 5 , wherein the nebulizer is a nebulizer with a nasal adapter.  
     
     
         9 . The method of  claim 5 , wherein the nebulizer is connected to a compressor.  
     
     
         10 . The method of  claim 5 , wherein the nebulizer delivers a majority of aerosolized particles in the size range of about 3.0 to about 3.5 μm in diameter.  
     
     
         11 . The method  claim 1 , wherein the pharmaceutical composition is administered to the patient 1-3 times a day for a total of 14-21 days.  
     
     
         12 . The method of  claim 1 , wherein the composition has a pH in the range of about 3.0 to about 8.5.  
     
     
         13 . The method of  claim 1 , wherein the osmotic pressure of the composition is between about 300 mOsm/kg to about 880 mOsm/kg.  
     
     
         14 . The method of  claim 1 , wherein the NaCl equivalency to the composition is between about 0.9% NaCl to about 3.0% NaCl.  
     
     
         15 . The method of  claim 1 , wherein the composition further comprises a decongestant.  
     
     
         16 . The method of  claim 1 , wherein the composition, when administered as an aerosolized spray, has minimal systemic side effects.  
     
     
         17 . The method of  claim 1 , wherein said active ingredient is an anti-infective agent and the sinusitis is caused by a pathogen selected from the group consisting of  Alpha Hemolytic streptococci, Beta Hemolytic streptococci, Branhamella Catarrhalis, Diptheroids, Haemophilis influenzae  (beta-lactamase positive and negative),  Moraxella species, Pseudomonas aeruginosa, Pseudomonas maltophilia, Serratia marcescens, Staphylococcus aureus, Streptococcus pneumonia, Aspergillosis, Mucor  and  Candida Albicans, Fusarium, Curvularia, cryptococcus, coccidioides  and  histoplasma.    
     
     
         18 . The method of  claim 17 , wherein said anti-infective agent is selected from the group consisting of Penicillins, Cephalosporins, Macrolides, Sulfonamides, Quinolones, Aminoglycosides, BetaLactam antibiotics, Linezolid, Vancomycin, Amphotericin B, and Azole antifungals.  
     
     
         19 . The method of  claim 2 , wherein said surfactant is a polysorbate.  
     
     
         20 . The method of  claim 5 , wherein the nebulizer delivers a majority of aerosolized particles in the size range of about 1.0 to about 4.0 μm in diameter.  
     
     
         21 . The method of  claim 5 , wherein the nebulizer delivers a majority of aerosolized particles in the size range of about 0.5 to about 5.0 μm in diameter.  
     
     
         22 . The method of  claim 5 , wherein the nebulizer delivers a majority of aerosolized particles in the size range of about 2.0 to about 3.5 μm in diameter.  
     
     
         23 . The method of  claim 5 , wherein the maximum number of particles delivered by the nebulizer over about 5.0 microns is less that 20% of the total particles.  
     
     
         24 . The method of  claim 1 , wherein the surface tension of the composition is between about 20 to about 60 dynes/cm.  
     
     
         25 . The method of  claim 1 , wherein the surface tension of the composition is between about 30 to about 50 dynes/cm.  
     
     
         26 . The method of  claim 1 , wherein the osmotic pressure of the composition is between about 150 mOsm/kg to about 880 mOsm/kg.  
     
     
         27 . The method of  claim 1 , wherein the osmotic pressure of the composition is between about 400 mOsm/kg to about 700 mOsm/kg.  
     
     
         28 . The method of  claim 1 , wherein the osmotic pressure of the composition is between about 500 mOsm/kg to about 600 mOsm/kg.  
     
     
         29 . The method of  claim 1 , wherein the NaCl equivalency to the composition is between about 1.1 % NaCl to about 1.8% NaCl.  
     
     
         30 . The method of  claim 1 , wherein the NaCl equivalency to the composition is between about 1.3% NaCl to about 1.7% NaCl.  
     
     
         31 . The method of  claim 4 , wherein the anti-inflammatory agent is a glucocorticoid, disodium cromoglycate or nedcromil sodium.  
     
     
         32 . The method of  claim 4 , wherein the mucolytic agent is acetylcysteine or dornase alpha.  
     
     
         33 . The method of  claim 15 , wherein the decongestant is phenylephrine, naphazoline, oxymetazoline, tetrahydrozoline or xylometoazoline.  
     
     
         34 . The method of  claim 1 , wherein the agent is amikacin, amphotericin B, azithromycin, aztreonam, cefazolin, cefepime, cefonicid, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cephapirin, ciprofloxacin, clindamycin, doxycycline, fluconazole, gentamycin, itraconazole, levofloxacin, meropenem, meziocillin, miconazole, nafcilin, oflaxacin, piperacillin, rifampin, ticarcillin+clavulanate, tobramycin or vancomycin.  
     
     
         35 . The method of  claim 2 , wherein the surfactant is PEG 400, sodium lauryl sulfate, span 20, span 40, span 60, Tween 20, Tween 40, Tween 60 or benzalkonium chloride.  
     
     
         36 . The method of  claim 2 , wherein the surfactant has a hydrophile-lipophile-balance (HLB) of between about 1.8 to about 8.6.  
     
     
         37 . The method of  claim 2 , wherein the surfactant has a hydrophile-lipophile-balance (HLB) of between about 9.6 to about 16.7.  
     
     
         38 . The method of  claim 2 , wherein the surfactant is Tween 20.