Therapeutic combination comprising a pulmonary surfactant and antioxidant enzymes

Abstract

Administration of an exogenous pulmonary surfactant in combination with antioxidant enzymes is effective for the prevention of bronchopulmonary dysplasia (BPD) and decreases the markers of pulmonary oxidative stress.

1 . A pharmaceutical composition, comprising:
 an exogenous pulmonary surfactant;   CuZn superoxide dismutase at a unit dose of from 2000 to 10000 U/kg; and   catalase at a unit dose of from 2000 to 4000 U/kg.   
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein said surfactant is a modified natural pulmonary surfactant. 
     
     
         3 . A pharmaceutical composition according to  claim 2 , wherein said surfactant is selected from the group of poractant alfa, calfactant, bovactant, and beractant. 
     
     
         4 . A pharmaceutical composition according to  claim 3 , wherein said surfactant is poractant alfa. 
     
     
         5 . A pharmaceutical composition according to  claim 4 , wherein poractant alfa is present in an amount of from 100 to 200 mg/kg. 
     
     
         6 . A pharmaceutical composition according to  claim 1 , wherein the unit dose of CuZn superoxide dismutase is from 2500 to 6000 U/kg. 
     
     
         7 . A pharmaceutical composition according to  claim 1 , wherein the unit dose of catalase is from 2500 to 3500 U/kg. 
     
     
         8 . A pharmaceutical composition according to  claim 1 , which is in the form of sterile suspension in a buffered physiological saline (0.9% w/v sodium chloride) aqueous solution. 
     
     
         9 . A kit comprising:
 (a) an exogenous pulmonary surfactant and a pharmaceutically acceptable carrier or diluent in a first unit dosage form;   (b) CuZn superoxide dismutase at a unit dose of from 2000 to 10000 U/kg, and optionally a pharmaceutically acceptable carrier or diluent in a second unit dosage form;   (c) catalase at a unit dose of from 2000 to 4000 U/kg, and optionally a pharmaceutically acceptable carrier or diluent in a third unit dosage form; and   (d) containers for containing said first, second, and third dosage forms.   
     
     
         10 . A kit according to  claim 9 , wherein the surfactant is a modified natural pulmonary surfactant. 
     
     
         11 . A kit according to  claim 9 , wherein the surfactant is poractant alfa. 
     
     
         12 . A method for reducing pulmonary oxidative damage, comprising administering:
 an effective amount of an exogenous pulmonary surfactant;   CuZn superoxide dismutase at a unit dose of from 2000 to 10000 U/kg; and   catalase at a unit dose of from 2000 to 4000 U/kg,   to a subject in need thereof.   
     
     
         13 . A method according to  claim 12 , wherein said surfactant is a modified natural pulmonary surfactant. 
     
     
         14 . A method according to  claim 13 , wherein said surfactant is selected from the group of poractant alfa, calfactant, bovactant, and beractant. 
     
     
         15 . A method according to  claim 14 , wherein said surfactant is poractant alfa. 
     
     
         16 . A method according to  claim 15 , wherein poractant alfa is present in an amount of from 100 to 200 mg/kg. 
     
     
         17 . A method according to  claim 12 , wherein the unit dose of CuZn superoxide dismutase is from 2500 to 6000 U/kg. 
     
     
         18 . A method according to  claim 12 , wherein the unit dose of catalase is from 2500 to 3500 U/kg. 
     
     
         19 . A method for reducing the risk of developing bronchopulmonary dysplasia, comprising administering:
 an effective amount of an exogenous pulmonary surfactant;   CuZn superoxide dismutase at a unit dose of from 2000 to 10000 U/kg; and   catalase at a unit dose of from 2000 to 4000 U/kg,   to a subject in need thereof.   
     
     
         20 . A method according to  claim 19 , wherein said surfactant is a modified natural pulmonary surfactant. 
     
     
         21 . A method according to  claim 20 , wherein said surfactant is selected from the group of poractant alfa, calfactant, bovactant, and beractant. 
     
     
         22 . A method according to  claim 21 , wherein said surfactant is poractant alfa. 
     
     
         23 . A method according to  claim 22 , wherein poractant alfa is present in an amount of from 100 to 200 mg/kg. 
     
     
         24 . A method according to  claim 23 , wherein the unit dose of CuZn superoxide dismutase is from 2500 to 6000 U/kg. 
     
     
         25 . A method according to  claim 19 , wherein the unit dose of catalase is from 2500 to 3500 U/kg. 
     
     
         26 . A method according to  claim 19 , wherein said subject is a preterm infant.