Methods and compositions for the treatment and prevention of lung disease

Abstract

Methods and compositions for the treatment of lung disease, such as emphysema and/or bronchopulmonary dysplasia, in a mammal. Also disclosed are methods promoting the formation of alveolar septa and increasing the gas-exchange surface area of a mammalian lung, and for the prevention and/or treatment of alveolar destruction.

What is claimed is:  
     
         1 . A composition for the treatment or prevention of alveolar destruction in a mammal comprising a pharmaceutically effective amount of an RAR β antagonist having RAR specific modulating activity.  
     
     
         2 . The composition of    claim 1    wherein said RARβ antagonist is not specific to RARα.  
     
     
         3 . The composition of    claim 1    wherein said RARβ antagonist is not specific to RARγ.  
     
     
         4 . The composition of    claim 1    wherein said RARβ antagonist is not specific to RARα or RARγ.  
     
     
         5 . The composition of    claim 1    wherein said composition further comprises said RARβ antagonist in dissolved form.  
     
     
         6 . The composition of    claim 5    wherein said RARβ antagonist is not specific to RARα.  
     
     
         7 . The composition of    claim 5    wherein said RARβ antagonist is not specific to RARγ.  
     
     
         8 . The composition of    claim 5    wherein said RARβ antagonist is not specific to RARα or RARγ.  
     
     
         9 . An aerosol for pulmonary delivery of a pharmaceutical composition, said pharmaceutical composition comprising an RAR β antagonist having specific RAR modulating activity.  
     
     
         10 . The aerosol of    claim 9    wherein said RARβ antagonist is not specific to RARα.  
     
     
         11 . The aerosol of    claim 9    wherein said RARβ antagonist is not specific to RARγ.  
     
     
         12 . The aerosol of    claim 9    wherein said RARβ antagonist is not specific to RARα or RARγ.  
     
     
         13 . A method for the treatment or prevention of alveolar destruction in a mammal comprising the step of administering a therapeutically effective amount of an RAR β antagonist specific RAR modulating activity to said mammal.  
     
     
         14 . The method of    claim 13   , wherein said RARβ antagonist is not specific to RARα.  
     
     
         15 . The method of    claim 13    wherein said RARβ antagonist is not specific to RARγ.  
     
     
         16 . The method of    claim 13    wherein said RARβ antagonist is not specific to RARα or RARγ.  
     
     
         17 . The method of    claim 13   , wherein said composition is administered in the form of an inhalant.  
     
     
         18 . The method of    claim 17    wherein said RARβ antagonist is not specific to RARα.  
     
     
         19 . The method of    claim 17    wherein said RARβ antagonist is not specific to RARγ.  
     
     
         20 . The method of    claim 17    wherein said RARβ antagonist is not specific to RARα or RARγ.  
     
     
         21 . A method to increase the gas-exchange surface area of a mammalian lung in a mammal in need thereof comprising the step of administering a therapeutically effective amount of an RAR β antagonist having specific RAR modulating activity to said mammal.  
     
     
         22 . The method of    claim 21   , wherein said RARβ antagonist is not specific to RARα.  
     
     
         23 . The method of    claim 21    wherein said RARβ antagonist is not specific to RARγ.  
     
     
         24 . The method of    claim 21    wherein said RARβ antagonist is not specific to RARα or RARγ.  
     
     
         25 . The method of    claim 21   , wherein said composition is administered in the form of an inhalant.  
     
     
         26 . The method of    claim 25    wherein said RARβ antagonist is not specific to RARα.  
     
     
         27 . The method of    claim 25    wherein said RARβ antagonist is not specific to RARγ.  
     
     
         28 . The method of    claim 25    wherein said RARβ antagonist is not specific to RARα or RARγ.  
     
     
         29 . The RARβ antagonist of any of the foregoing claims, comprising the structural formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 a) X is selected from the group consisting of CR 2 , O, S, and NR;  
 b) R′ and R″ are each independently selected from the group consisting of H and lower alkyl;  
 c) Ar and Ar′ are each independently a single ring aryl moiety; and  
 d) B is selected from the group consisting of —CR′CH—, —CHCR′—, —COO—, —OOC—; —COHN—; —NHOC—; —CSHN—; and —NHSC—.  
 
     
     
         30 . The RARβ antagonist of    claim 29    wherein Ar and Ar′ are each independently selected from the group consisting of substituted or unsubstituted phenyl, furyl, thienyl and pyridyl groups.