Compositions containing lysophosphatidic acids which inhibit apoptosis and uses thereof

Abstract

The invention provides anti-apoptotic compositions containing lysophosphatidic acids and methods for making and using the compositions. Such compositions may also contain LPA potentiating agents, including proteins, lipid membrane structures and polymers such as polyethylene glycols. The compositions can additionally contain other pharmaceutically effective agents such as drugs, antibiotics, wound healing agents and antioxidants.

1 - 57 . (canceled)  
     
     
         58 . A compound of the following formula:  
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein, 
 each W is independently OH, OCH 2 CH(NH 2 )CO 2 H, OCHCH 3 CH(NH 2 )CO 2 H, OPO 3 H 2 , or OP(O)(OH)—O—PO 3 H 2 , and  
 Q is the following structure:  
                     
 wherein,  
 Y is O or S;  
 R is substituted or unsubstituted, saturated or unsaturated, straight or branched-chain alkyl, or ((CH 2 ) p O) q (CH 2 ) p T where q is an integer from 1 to 900 and where each p is independently an integer from 2 to 10 and T is OH, or O(CH 2 ) b CH 3  where b is an integer from 0 to 10;  
 V is independently OH, SH, H, NH 2 , halogen, OPO 3 H 2 , or OSO 3 H;  
 n is an integer from 0 to 10;  
 m is an integer from 0 to 10;  
 Z is OH, SH, NH 2 , OPO 3 H 2 , halogen, HN, O(CH 2 ) d CH 3  where d=0 to 2, or SO 3 H; and  
 L is independently O or S.  
 
     
     
         59 . A composition comprising a compound of  claim 58 , and at least one pharmaceutically acceptable excipient.  
     
     
         60 . A method of making a composition comprising a compound of  claim 58  and a potentiating component, comprising: 
 a) forming a lipid dispersion comprising a compound of  claim 58;     b) combining the lipid dispersion with at least one potentiating component to form a composition.    
     
     
         61 . The method according to  claim 60 , wherein the lipid dispersion is formed by: 
 a) dissolving a compound of  claim 58  and any other lipids in organic solvent;    b) removing the solvent from any lipid compounds dissolved therein to form dried lipid; and,    c) dispersing the dried lipid into aqueous media by the steps of: 
 i) forming an even lipid dispersion; and  
 ii) forming an even dispersion of lipid membrane structures.  
   
     
     
         62 . The method according to  claim 60 , further comprising the step of 
 c) sterilizing the composition.    
     
     
         63 . A method of inhibiting apoptosis of fibroblasts comprising contacting fibroblasts with a compound of  claim 58 .  
     
     
         64 . A method of culturing cells comprising contacting cells in culture with a compound of  claim 58 .  
     
     
         65 . A method of inhibiting apoptosis of cells present within an organ that has been removed from a donor comprising contacting said organ with a compound according to  claim 58 .  
     
     
         66 . A method of inhibiting apoptosis of cells present within an organ of a donor comprising administering to said donor at least one intravenous bolus of an effective amount of a compound according to  claim 58 .  
     
     
         67 . A compound of  claim 58 , wherein R is substituted or unsubstituted, saturated or unsaturated, straight or branched-chain alkyl having from about 5 to 30 carbons.  
     
     
         68 . A compound of  claim 58 , wherein R is substituted or unsubstituted, saturated or unsaturated, straight or branched-chain alkyl having about 10 carbons.