Choline Esters

Abstract

Compounds, formulations, and methods are provided containing the choline ester of a reducing agent, especially lipoic acid or derivatives thereof. The compounds may be administered via a topical ocular route to treat or prevent oxidative damage.

1 . A compound comprising the choline ester of lipoic acid or a derivative of lipoic acid. 
     
     
         2 . The compound of  claim 1 , wherein the lipoic acid is alpha lipoic acid. 
     
     
         3 . (canceled) 
     
     
         4 . The compound of  claim 1 , wherein the lipoic acid or derivative of lipoic acid includes the R enantiomer. 
     
     
         5 . A pharmaceutical composition comprising an active agent that is a reducing agent-choline ester at least one pharmaceutically acceptable excipient. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the reducing agent is lipoic acid or a derivative thereof. 
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein the active agent is lipoic acid choline ester. 
     
     
         8 . The pharmaceutical composition of  claim 5 , wherein the active agent is present in an amount of about 0.1% to about 10%. 
     
     
         9 . (canceled) 
     
     
         10 . The pharmaceutical composition of  claim 5 , wherein the at least one pharmaceutically acceptable excipient is selected from the group consisting of a buffer, a tonicity agent, and a viscosity agent. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the buffer is a phosphate buffer. 
     
     
         12 . The pharmaceutical composition of  claim 10 , wherein the viscosity agent is a cellulosic agent. 
     
     
         13 . The pharmaceutical composition of  claim 5 , comprising a biochemical energy source which is alanine. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . A pharmaceutical composition comprising:
 about 0.25% to about 10% of a reducing agent-choline ester,   optionally, about 0.05% to about 1.0% of a biochemical energy source,   about 0.25% to about 1% buffer,   about 0.2% to about 0.6% tonicity agent, and   about 0.1% to about 0.4% viscosity agent.   
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . A method of preventing or treating oxidation damage to cells comprising
 administering a pharmaceutical composition of  claim 5 .   
     
     
         23 - 26 . (canceled) 
     
     
         27 . A method for preparing a choline ester comprising:
 providing a reducing agent; and   reacting the reducing agent with a halogenated choline to yield a choline ester.   
     
     
         28 . The method of  claim 27 , wherein the reducing agent is lipoic acid. 
     
     
         29 . The method of  claim 27 , wherein the halogenated choline is bromocholine bromide. 
     
     
         30 . The method of  claim 27 , wherein the reacting step further includes a base. 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 27  wherein the method is conducted in a solvent selected from acetone and dimethyl formamide. 
     
     
         33 . The method of  claim 30 , wherein the base is selected from K 2 CO 3 , Cs 2 CO 3 , KF, NaHCO 3  and KH 2 PO 4 . 
     
     
         34 . The method of  claim 30  wherein the base is present in an amount of about 1 to about 5 equivalents relative to the reducing agent.