Nuclear sulfated oxysterol, potent regulator of lipid homeostasis, for therapy of hypercholesterolemia, hypertriglycerides, fatty liver diseases, and atherosclerosis
The sulfated oxysterol 5-cholesten-3β, 25-diol 3-sulphate, a nuclear cholesterol metabolite that decreases lipid biosynthesis and increases cholesterol secretion and degradation, is provided as an agent to lower intracellular and serum cholesterol and/or triglycerides, and to prevent or treat lipid accumulation-associated inflammation and conditions associated with such inflammation. Methods which involve the use of this sulfated oxysterol to treat conditions associated with high cholesterol and/or high triglycerides and/or inflammation (e.g. hypercholesterolemia, hypertriglyceridemia, non-alcoholic fatty liver diseases, atherosclerosis, etc.) are also provided.
1. A pharmaceutically acceptable salt of a compound of formula:
wherein the pharmaceutically acceptable salt is in solid form.
2. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is a sodium salt.
3. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is in substantially purified form.
4. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is in a form that is at least 80% free from other chemical species.
5. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is in a form that is at least 90% free from other chemical species.
6. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is in a form that is at least 95% free from other chemical species.
7. The pharmaceutically acceptable salt of claim 2 , wherein the pharmaceutically acceptable salt is in substantially purified form.
8. The pharmaceutically acceptable salt of claim 2 , wherein the pharmaceutically acceptable salt is in a form that is at least 80% free from other chemical species.
9. The pharmaceutically acceptable salt of claim 2 , wherein the pharmaceutically acceptable salt is in a form that is at least 90% free from other chemical species.
10. The pharmaceutically acceptable salt of claim 2 , wherein the pharmaceutically acceptable salt is in a form that is at least 95% free from other chemical species.
11. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is in powder form.
12. A method of making a compound of the formula:
comprising
sulfating a 3β position of 25-hydroxycholesterol.
13. The method of claim 12 , wherein said sulfating is performed by forming a mixture of said 25-hydroxycholesterol with sulfur trioxide triethyl amine complex and incubating said mixture under conditions whereby said 3β position of said 25-hydroxycholesterol is sulfated.
14. The method of claim 12 , further comprising purifying said compound by flash chromatography.
15. The method of claim 12 , further comprising purifying said compound by high performance liquid chromatography (HPLC).