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 method of decreasing fat accumulation in liver cells of a patient in need thereof, comprising:
intravenously administering to the patient a composition comprising 5-cholesten-3β, 25-diol 3-sulphate or a pharmaceutically acceptable salt thereof in an amount sufficient to decrease fat accumulation in the liver cells of the patient, a buffer, and water.
2. The method of claim 1 , wherein the 5-cholesten-3β, 25-diol 3-sulphate or a pharmaceutically acceptable salt thereof is a salt of 5-cholesten-3β, 25-diol 3-sulphate.
3. The method of claim 2 , wherein the salt is selected from a sodium salt, a potassium salt, a calcium salt, a lithium salt, and an ammonium salt.
4. The method of claim 3 , wherein the salt is a sodium salt.
5. The method of claim 1 , wherein the 5-cholesten-3β, 25-diol 3-sulphate or a pharmaceutically acceptable salt thereof is present in an amount ranging from 1% to 99% of the composition.
6. The method of claim 1 , wherein the buffer is present in an amount ranging from 1% to 99% of the composition.
7. The method of claim 1 , wherein the water is present in an amount ranging from 1% to 99% of the composition.
8. The method of claim 1 , wherein the 5-cholesten-3β, 25-diol 3-sulphate or a pharmaceutically acceptable salt thereof is administered in an amount ranging from 0.1 μg/kg/24 hours to 100 μg/kg/24 hours.
9. The method of claim 1 , wherein the 5-cholesten-3β, 25-diol 3-sulphate or a pharmaceutically acceptable salt thereof is administered in an amount ranging from 0.1 μg/kg/24 hours to 50 μg/kg/24 hours.
10. The method of claim 1 , wherein the 5-cholesten-3β, 25-diol 3-sulphate or a pharmaceutically acceptable salt thereof is administered in an amount ranging from 0.1 μg/kg/24 hours to 10 μg/kg/24 hours.
11. The method of claim 4 , wherein the sodium salt of 5-cholesten-3β, 25-diol 3-sulphate is present in an amount ranging from 1% to 99% of the composition.
12. The method of claim 11 , wherein the buffer is present in an amount ranging from 1% to 99% of the composition.
13. The method of claim 11 , wherein the water is present in an amount ranging from 1% to 99% of the composition.
14. The method of claim 4 , wherein the sodium salt of 5-cholesten-3β, 25-diol 3-sulphate is administered in an amount ranging from 0.1 μg/kg/24 hours to 100 μg/kg/24 hours.
15. The method of claim 4 , wherein the sodium salt of 5-cholesten-3β, 25-diol 3-sulphate is administered in an amount ranging from 0.1 μg/kg/24 hours to 50 μg/kg/24 hours.
16. The method of claim 4 , wherein the sodium salt of 5-cholesten-3β, 25-diol 3-sulphate thereof is administered in an amount ranging from 0.1 μg/kg/24 hours to 10 μg/kg/24 hours.
17. The method of claim 1 , wherein the patient has hepatitis.
18. The method of claim 2 , wherein the patient has hepatitis.
19. The method of claim 4 , wherein the patient has hepatitis.
20. The method of claim 10 , wherein the patient has hepatitis.