Pharmaceutical Compositions

Abstract

The invention provides compositions comprising formula 1 steroids, e.g., 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate and one or more excipients, typically wherein the composition comprises less than about 3% water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16α-bromo-3β-hydroxy-5α-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen (viral) replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using certain steroids and steroid analogs. The invention also provides methods to make and use these immunomodulatory compositions and formulations.

1 . A solid or liquid pharmaceutical formulation comprising one or more excipients and a compound having the formula  
       
         
           
           
               
               
           
         
         wherein  
         R 1 , R 2 , R 3  and R 4  independently are —OH, an ester or an ether;  
         R 5  is —CH 3  or —CH 2 OH;  
         R 6  is —H, —CH 3  or —CH 2 OH; and  
         R 8  is —CH 2 — or —CHR 10 — where R 10  is —OH, —SH or C 1-10  optionally substituted alkyl.  
       
     
     
         2 . The pharmaceutical formulation of  claim 1  wherein R 1 , R 2 , R 3  and R 4  are —OH.  
     
     
         3 . The pharmaceutical formulation of  claim 2  wherein R 5  is —CH 3 .  
     
     
         4 . The pharmaceutical formulation of  claim 3  wherein R 6  is —H or —CH 3 .  
     
     
         5 . The pharmaceutical formulation of  claim 4  wherein the compound has the formula  
       
         
           
           
               
               
           
         
       
     
     
         6 . The pharmaceutical formulation of  claim 5  wherein the compound is androst-5-ene-3β,7β,16α,17β-tetrol, androst-5-ene-3β,7α,16α,17β-tetrol or androst-5-ene-3β,7β,16β,17β-tetrol.  
     
     
         7 . A compound having the formula  
       
         
           
           
               
               
           
         
         wherein  
         R 1 , R 2 , R 3  and R 4  independently are —OH, an ester or an ether;  
         R 5  is —CH 3  or —CH 2 OH;  
         R 6  is —H, —CH 3  or —CH 2 OH; and  
         R 3  is —CH 2 — or —CHR 10 — where R 10  is —OH, —SH or C 1-10  optionally substituted alkyl, wherein the compound is a powder or granule.  
       
     
     
         8 . The compound of  claim 7  wherein R 1 , R 2 , R 3  and R 4  are —OH.  
     
     
         9 . The compound of  claim 8  wherein R 5  is —CH 3 .  
     
     
         10 . The compound of  claim 9  wherein R 6  is —H or —CH 3 .  
     
     
         11 . The compound of  claim 10  wherein the compound has the formula  
       
         
           
           
               
               
           
         
       
     
     
         12 . The compound of  claim 11  wherein the compound is androst-5-ene-3β,7β,16α,17β-tetrol, androst-5-ene-3β,7α,16α,17β-tetrol or androst-5-ene-3β,7β,16β,17β-tetrol.