Compounds and compositions
View Patent ↗The invention provides compositions comprising formula 1 steroids, e.g., 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate and one or more excipients, including compositions that comprise a liquid formulation comprising less than about 3% v/v 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 replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using the compounds. The invention also provides methods to make and use these immunomodulatory compositions and formulations.
1. A pharmaceutical formulation comprising one or more excipients and a compound having the structure
wherein
R 1 and R 4 independently are —OH, an ester or an ether;
R 2 is —H, —OH, an ester or an ether
R 3 is —OH, an ester, an ether or halogen; and
R 8 is —O— or —CHR 10 — wherein R 10 is —OH.
2. The formulation of claim 1 wherein R 1 , R 2 and R 4 are —OH or an ester and R 3 is —OH, an ester or —Br.
3. The formulation of claim 2 wherein the compound has the structure
4. The formulation of claim 2 wherein the compound has the structure
5. The formulation of claim 3 wherein the compound has the structure
6. The formulation of claim 5 wherein R 1 , R 2 and R 4 are —OH and R 3 is —OH or —Br.
7. The formulation of claim 1 wherein the formulation is for oral administration.
8. The formulation of claim 6 wherein the formulation is for oral administration.
9. A compound having the structure
wherein
R 1 , R 2 and R 4 independently are —OH, an ester or an ether;
R 3 is —OH, an ester, an ether or halogen
R 5 is —CH 3 or —CH 2 OH; and
R 6 is —H, —CH 3 or —CH 2 OH.
10. The compound of claim 9 wherein R 1 , R 2 and R 4 are —OH or an ester and R 3 is —OH, an ester or —Br.
11. The compound of claim 10 wherein R 5 is —CH 3 .
12. The compound of claim 11 wherein R 6 is —H or —CH 3 .
13. The compound of claim 10 wherein the compound has the structure
14. The compound of claim 10 wherein the compound has the structure
15. The compound of claim 13 wherein the compound has the structure
16. The compound of claim 15 wherein R 1 , R 2 and R 4 are —OH and R 3 is —OH or Br.
17. The compound of claim 16 wherein the compound has the structure
18. The formulation of claim 6 wherein the compound has the structure