Enteric-coated ht-2157 compositions and methods of their use

Abstract

Drug compositions comprising the compound HT-2157 and their therapeutic uses, including the treatment of CNS disorders and cognitive impairments and the modulation of cognitive function, are disclosed. More particularly, the present invention relates to enteric-coated formulations comprising HT-2157 that reduce the appearance of clinically relevant methemoglobinemia relative to administration of non-enteric-coated formulations comprising HT-2157.

What is claimed is: 
     
         1 . A composition comprising a solid-dosage form, wherein said solid-dosage form comprises:
 (a) a therapeutically effective amount of HT-2157, which has the following structure:   
       
         
           
           
               
               
           
         
       
       and
 (b) an enteric coating. 
 
     
     
         2 . The composition of  claim 1 ,
 wherein said administration of the enteric-coated composition to a subject reduces appearance of clinically relevant methemoglobinemia, relative to administration of a non-enteric coated composition comprising the same amount of HT-2157.   
     
     
         3 . The composition of  claim 1 ,
 wherein said administration of the enteric-coated composition to a subject results in a lower increase in percent of methemoglobin, relative to administration of a non-enteric coated composition comprising the same amount of HT-2157.   
     
     
         4 . The composition of  claim 3 ,
 wherein said administration of the enteric-coated composition increases methemoglobin levels to less than about 3 percent.   
     
     
         5 . The composition of  claim 3 ,
 wherein said administration of the enteric-coated composition increases methemoglobin levels to less than about 1.5 percent.   
     
     
         6 . The composition of  claim 1 , wherein the enteric coating comprises a methacrylic polymer 
     
     
         7 . The composition of  claim 1 , further comprising one or more excipients selected from the following: a diluent, a binder, a surfactant, a glidant, and a lubricant. 
     
     
         8 . The composition of  claim 1 , wherein the composition remains stable after about 1 year of storage at 25° C./60% RH or after about 6 months of storage at 40° C./75% RH. 
     
     
         9 . A method comprising:
 (a) administering the composition of  claim 1  to a subject;   (b) reducing appearance of clinically relevant methemoglobinemia, relative to administration of a non-enteric coated composition comprising the same amount of HT-2157.   
     
     
         10 . A method comprising:
 administering the composition of  claim 1  to a subject,   wherein said administering results in a lower increase in percent of methemoglobin, relative to administration of a non-enteric coated composition comprising the same amount of HT-2157.   
     
     
         11 . The method of  claim 10 ,
 wherein said administration of the enteric coated composition increases methemoglobin levels to less than about 3 percent.   
     
     
         12 . The method of  claim 10 ,
 wherein said administration of the enteric coated composition increases methemoglobin levels to less than about 1.5 percent.   
     
     
         13 . The method of  claim 9 ,
 wherein the enteric coating of the composition administered in step (a) comprises a methacrylic polymer.   
     
     
         14 . The method of  claim 9 ,
 wherein the composition administered in step (a) further comprises one or more excipients selected from the following: a diluent, a binder, a surfactant, a glidant, and a lubricant.   
     
     
         15 . The method of  claim 9 , wherein the composition administered in step (a) remains stable after about 1 year of storage at 25° C./60% R.H or after about 6 months of storage at 40° C./75% R.H. 
     
     
         16 . A method of treating a CNS disorder comprising administering the composition of  claim 1  to a subject in need thereof. 
     
     
         17 . The method of  claim 16 , wherein the CNS disorder is depression or anxiety. 
     
     
         18 . A method comprising the steps of:
 (a) providing cognitive training to an animal in need of treatment of a cognitive impairment under conditions sufficient to produce an improvement in performance by said animal of a cognitive function whose deficit is associated with said cognitive impairment;   (b) administering the composition of  claim 1  to said animal in conjunction with said cognitive training;   (c) repeating said providing and said administering of steps (a) and (b) one or more times; and   (d) reducing the number of training sessions sufficient to produce said improvement in performance, relative to the improvement in performance produced by cognitive training alone.   
     
     
         19 . The method of  claim 18 , wherein said administering reduces appearance of clinically relevant methemoglobinemia or results in a lower increase in percent of methemoglobin, relative to administration of a non-enteric coated composition comprising the same amount of HT-2157. 
     
     
         20 . The method of  claim 18 , wherein the cognitive impairment includes a memory impairment.