Thermoreversible compositions for administration of therapeutic agents

Abstract

The present invention relates to compositions and methods of inducing the self-renewal of stem/progenitor supporting cells, including inducing the stem/progenitor cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into hair cells.

1 - 520 . (canceled) 
     
     
         521 . A pharmaceutical composition comprising:
 a) a 2-pyrimidinylaminoethylamino-2-pyridine compound;   b) Poloxamer 407; and   c) a carboxylic acid containing compound, or a pharmaceutically acceptable salt thereof;   wherein the pharmaceutical composition has a gelation temperature of greater than 10° C.   
     
     
         522 . The pharmaceutical composition of  claim 521 , wherein the 2-pyrimidinylaminoethylamino-2-pyridine compound is a 2,4-dichlorophenyl-5-(1H-imidazol-2-yl)-2-pyrimidinylaminoethylamino-2-pyridine compound. 
     
     
         523 . The pharmaceutical composition of  claim 521 , wherein the 2-pyrimidinylaminoethylamino-2-pyridine compound is 6-[[2-[[4-(2,4-Dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)-2-pyrimidinyl]amino]ethyl]amino]-3-pyridinecarbonitrile, having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         524 . The pharmaceutical composition of  claim 521 , wherein the Poloxamer 407 is present at a concentration of great than or equal to 21 wt %. 
     
     
         525 . The pharmaceutical composition of  claim 521 , wherein the Poloxamer 407 is present at a concentration of about 23 wt % to about 29 wt %. 
     
     
         526 . The pharmaceutical composition of  claim 521 , wherein the carboxylic acid containing compound is a substituted or unsubstituted C 5 -C 9  straight or branched chain alkyl-CO 2 H. 
     
     
         527 . The pharmaceutical composition of  claim 521 , wherein the carboxylic acid containing compound is valproic acid. 
     
     
         528 . The pharmaceutical composition of  claim 521 , wherein the pharmaceutical composition has a gelation temperature of about 11° C. and about 32° C. 
     
     
         529 . A pharmaceutical composition comprising:
 a) a 2-pyrimidinylaminoethylamino-2-pyridine compound;   b) Poloxamer 407, wherein the Poloxamer 407 is present at a concentration of greater than or equal to 21 wt %; and   c) a carboxylic acid containing compound, or a pharmaceutically acceptable salt thereof.   
     
     
         530 . The pharmaceutical composition of  claim 529 , wherein the pharmaceutical composition has a gelation temperature of greater than 10° C. 
     
     
         531 . The pharmaceutical composition of  claim 529 , wherein the pharmaceutical composition has a gelation temperature of about 11° C. and about 32° C. 
     
     
         532 . The pharmaceutical composition of  claim 529 , wherein the 2-pyrimidinylaminoethylamino-2-pyridine compound is a 2,4-dichlorophenyl-5-(1H-imidazol-2-yl)-2-pyrimidinylaminoethylamino-2-pyridine compound. 
     
     
         533 . The pharmaceutical composition of  claim 529 , wherein the 2-pyrimidinylaminoethylamino-2-pyridine compound is 6-[[2-[[4-(2,4-Dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)-2-pyrimidinyl]amino]ethyl]amino]-3-pyridinecarbonitrile, having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         534 . The pharmaceutical composition of  claim 529 , wherein the Poloxamer 407 is present at a concentration of about 23 wt % to about 29 wt %. 
     
     
         535 . The pharmaceutical composition of  claim 529 , wherein the carboxylic acid containing compound is a substituted or unsubstituted C 5 -C 9  straight or branched chain alkyl-CO 2 H. 
     
     
         536 . The pharmaceutical composition of  claim 529 , wherein the carboxylic acid containing compound is valproic acid.