Compounds and methods for the treatment of airway diseases and for the delivery of airway drugs

Abstract

Chronic obstructive airway diseases are treated by administering an osmotically active compound such as a salt, sugar, sugar alcohol, or organic osmolyte to the afflicted airway surface. The compound may be administered as a liquid or dry powder aerosol formulation. Diseases that can be treated by the method include cystic fibrosis, chronic bronchitis, and ciliary dyskinesia. The formulations of the invention can also be used in conjunction with other active agents such as bronchodilators, sodium channel blockers, antibiotics, enzymes, or purinoceptor agonists on airway surfaces.

1 - 29 . (canceled)  
     
     
         30 . A method of treating chronic obstructive pulmonary disease in a subject in need of such treatment, comprising administering at least one osmotically active compound to an airway surface of the subject in an amount effective to increase the volume of liquid on the airway surface, wherein the at least one osmotically active compound comprises at least one salt comprising: 
 (a) a pharmaceutically acceptable anion selected from the group consisting of acetate, benzenesulfonate, benzoate, bitartrate, bromide, calcium edetate, camsylate, carbonate, chloride, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsylate, nitrate, pamoate, pantothenate, phosphate or diphosphate, polygalacturonate, salicylate, stearate, subacetate, succinate, sulfate, tannate, tannate, teoclate and triethiodide; and    (b) a pharmaceutically acceptable cation selected from the group consisting of benzathine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine, procaine, D-Lysine, L-lysine, D-arginine, L-arginine, uiethylammonium, N-methyl Do glycerol, aluminum, calcium, lithium, magnesium, potassium, sodium, zinc, iron, and ammonium.    
     
     
         31 . The method according to  claim 30 , wherein the subject is afflicted with one or more chronic obstructive pulmonary diseases selected from the group consisting of cystic fibrosis, chronic bronchitis and ciliary dyskinesia.  
     
     
         32 . The method according to  claim 30 , wherein the airway surface is a pulmonary airway surface.  
     
     
         33 . The method according to  claim 30 , wherein the airway surface is a nasal airway surface or sinus airway surface.  
     
     
         34 . The method according to  claim 30 , wherein said administering step of the at least one osmotically active compound is an aerosol inhalation administering step.  
     
     
         35 . The method according to  claim 30 , wherein said at least one salt comprises: 
 an anion selected from the group consisting of sulfate, nitrate, gluconate, iodide, chloride, bromide, and phosphate; and    a cation selected from the group consisting of choline, lithium, meglumine, D-lysine, ammonium, sodium, magnesium calcium, and potassium.    
     
     
         36 . The method according to  claim 30 , wherein said at least one salt is sodium chloride.  
     
     
         37 . The method according to  claim 30 , wherein said at least one salt is sodium nitrate.  
     
     
         38 . The method according to  claim 30 , wherein the method further comprises administering a bronchodilator to said subject prior to or concurrently with said at least one osmotically active compound in an amount sufficient to inhibit bronchoconstriction.  
     
     
         39 . The method of  claim 38 , wherein the bronchodilator is selected from the group consisting of  1 -adrenergic agonists, anticholinergic agonists and xanthine derivatives.  
     
     
         40 . The method according to  claim 39 , wherein the β-adrenergic agonist is epinephrine, isoproterenol, albuterol, terbutaline, pirbuterol, metaproteronol or salmeterol.  
     
     
         41 . The method according to  claim 30 , wherein the method further comprises administering agents selected from the group consisting of an enzyme drug, an anti-inflammatory agent, an antibiotic, an antiviral agent, an anti-neoplastic agent, an antihistamine, an anti- pneumocystis carinii  pneumonia agent, an anti-tuberculosis agent, an expectorant and a chelator of divalent cations.  
     
     
         42 . The method according to  claim 41 , wherein the enzyme drug is DNase or α 1 -antitrypsin.  
     
     
         43 . The method according to  claim 41 , wherein the antibiotic is tetracycline, choramphenicol, an aminoglycosides, a beta-lactam, a cephalosporin, erythromycin or clindamycin.