Treatment of ischemic brain injuries with brain targeted antioxidant compounds

Abstract

A method of reducing oxidative stress in the brain of an organism having a blood brain barrier and suffering an ischemic brain injury, the method comprising the step of administering a compound to the organism, the compound having (a) a combination of molecular weight and membrane miscibility properties for permitting the compound to cross the blood brain barrier of the organism; (b) a readily oxidizable chemical group for exerting antioxidation properties; and (c) a chemical make-up for permitting the compound or its intracellular derivative to accumulate within the cytoplasm of cells.

What is claimed is:  
     
         1 . A method of reducing oxidative stress in the brain of an organism having a blood brain barrier and suffering an ischemic brain injury, the method comprising the step of administering a compound to the organism, said compound having: 
 (a) a combination of molecular weight and membrane miscibility properties for permitting said compound to cross the blood brain barrier of the organism;    (b) a readily oxidizable chemical group for exerting antioxidation properties; and    (c) a chemical make-up for permitting said compound or its intracellular derivative to accumulate within the cytoplasm of cells.    
     
     
         2 . The method of  claim 1 , wherein said compound is selected from the group consisting of N-acetyl cysteine ethyl ester (compound A), β,β-dimethyl cysteine ethyl ester (compound B), N-acetyl-β,β-dimethyl cysteine (compound C), Glutathione ethyl ester (compound D), N-acetyl glutathione ethyl ester (compound E), N-acetyl glutathione (compound F), N-acetyl α-glutamyl ethyl ester cysteinyl glycyl ethyl ester (compound G) N-acetyl α-glutamyl ethyl ester cysteinyl glycyl (compound H), N-acetyl glutathione amide (compound I), N-acetyl cysteine amide (compound J), N-acetyl β,β dimethyl cysteine amide (compound K) and N-acetyl cysteine glycine amide.  
     
     
         3 . The method of  claim 1 , wherein said readily oxidizable chemical group is a sulfhydril group.  
     
     
         4 . The method of  claim 1 , wherein said chemical make-up is selected having an ester moiety which is removable by hydrolysis imposed by intracellular esterases.  
     
     
         5 . The method of  claim 1 , wherein said administration is peripheral.  
     
     
         6 . The method of  claim 4 , wherein said ester moiety is selected from the group consisting of alkyl ester and aryl ester.  
     
     
         7 . The method of  claim 6 , wherein said alkyl and aryl esters are selected from the group consisting of methyl ester, ethyl ester, hydroxyethyl ester, t-butyl ester, cholesteryl ester, isopropyl ester and glyceryl ester.  
     
     
         8 . The method of  claim 1 , wherein said organism is a human being.  
     
     
         9 . A method of therapeutically or prophylactically treating an individual against ischemic brain injury, the method comprising the step of administering to the individual a pharmaceutical composition to the individual, said pharmaceutical composition including a pharmaceutically acceptable carrier and a therapeutically or prophylactically effective amount of an antioxidant compound, said antioxidant compound having: 
 (a) a combination of molecular weight and membrane miscibility properties for permitting said compound to cross the blood brain barrier of the individual;    (b) a readily oxidizable chemical group for exerting antioxidation properties; and    (c) a chemical make-up for permitting said compound or its intracellular derivative to accumulate within brain cells of the individual.    
     
     
         10 . The method of  claim 9 , wherein said compound is selected from the group consisting of N-acetyl cysteine ethyl ester (compound A), β,β-dimethyl cysteine ethyl ester (compound B), N-acetyl-β,β-dimethyl cysteine (compound C), Glutathione ethyl ester (compound D), N-acetyl glutathione ethyl ester (compound E), N-acetyl glutathione (compound F), N-acetyl α-glutamyl ethyl ester cysteinyl glycyl ethyl ester (compound G) N-acetyl α-glutamyl ethyl ester cysteinyl glycyl (compound H), N-acetyl glutathione amide (compound I), N-acetyl cysteine amide (compound J), N-acetyl β,β dimethyl cysteine amide (compound K) and N-acetyl cysteine glycine amide.  
     
     
         11 . The method of  claim 9 , wherein said ischemic brain injury is a result of a stroke or a head trauma.  
     
     
         12 . The method of  claim 9 , wherein said pharmaceutically acceptable carrier is selected from the group consisting of a thickener, a carrier, a buffer, a diluent, a surface active agent and a preservatives.  
     
     
         13 . The method of  claim 9 , wherein said administration is peripheral.  
     
     
         14 . The method of  claim 13 , wherein said peripheral administration is selected from the group consisting of topical administration, oral administration, administration by inhalation, and parenteral administration.  
     
     
         15 . The method of  claim 9 , wherein said readily oxidizable chemical group is a sulfhydril group.  
     
     
         16 . The method of  claim 9 , wherein said chemical make-up is selected having an ester moiety which is removable by hydrolysis imposed by intracellular esterases.  
     
     
         17 . The method of  claim 9 , wherein said administration is peripheral.  
     
     
         18 . The method of  claim 16 , wherein said ester moiety is selected from the group consisting of alkyl ester and aryl ester.  
     
     
         19 . The method of  claim 18 , wherein said alkyl and aryl esters are selected from the group consisting of methyl ester, ethyl ester, hydroxyethyl ester, t-butyl ester, cholesteryl ester, isopropyl ester and glyceryl ester.  
     
     
         20 . The method of  claim 9 , wherein said organism is a human being.  
     
     
         21 . A pharmaceutical composition for therapeutically or prophylactically treating an individual against ischemic brain injury, the composition comprising a pharmaceutically acceptable carrier and, as an active ingredient, a therapeutically or prophylactically effective amount of an antioxidant compound, said compound having: 
 (a) a combination of molecular weight and membrane miscibility properties for permitting said compound to cross the blood brain barrier of the individual;    (b) a readily oxidizable chemical group for exerting antioxidation properties; and    (c) a chemical make-up for permitting said compound or its intracellular derivative to accumulate within brain cells of the individual.    
     
     
         22 . The method of  claim 21 , wherein said compound is selected from the group consisting of N-acetyl cysteine ethyl ester (compound A), β,β-dimethyl cysteine ethyl ester (compound B), N-acetyl-β,β-dimethyl cysteine (compound C), Glutathione ethyl ester (compound D), N-acetyl glutathione ethyl ester (compound E), N-acetyl glutathione (compound F), N-acetyl α-glutamyl ethyl ester cysteinyl glycyl ethyl ester (compound G) N-acetyl α-glutamyl ethyl ester cysteinyl glycyl (compound H), N-acetyl glutathione amide (compound I), N-acetyl cysteine amide (compound J), N-acetyl β,β dimethyl cysteine amide (compound K) and N-acetyl cysteine glycine amide.  
     
     
         23 . The method of  claim 21 , wherein said ischemic brain injury is a result of a stroke or a head trauma.  
     
     
         24 . The method of  claim 21 , wherein said pharmaceutically acceptable carrier is selected from the group consisting of a thickener, a carrier, a buffer, a diluent, a surface active agent and a preservatives.  
     
     
         25 . The method of  claim 21 , wherein said readily oxidizable chemical group is a sulfhydril group.  
     
     
         26 . The method of  claim 21 , wherein said chemical make-up is selected having an ester moiety which is removable by hydrolysis imposed by intracellular esterases.  
     
     
         27 . The method of  claim 26 , wherein said ester moiety is selected from the group consisting of alkyl ester and aryl ester.  
     
     
         28 . The method of  claim 27 , wherein said alkyl and aryl esters are selected from the group consisting of methyl ester, ethyl ester, hydroxyethyl ester, t-butyl ester, cholesteryl ester, isopropyl ester and glyceryl ester.