COMPOSITIONS COMPRISING 5-CHOLESTEN-3, 25-DIOL, 3-SULFATE (25HC3S) OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AND AT LEAST ONE CYCLIC OLIGOSACCHARIDE
Compositions comprising 5-cholesten-3, 25-diol, 3-sulfate (25HC3S) or pharmaceutically acceptable salt thereof and at least one cyclic oligosaccharide, e.g., a cyclodextrin (CD), are provided. The compositions may be used to prevent and/or treat a variety of diseases and conditions, including organ failure (e.g. acute liver failure), high cholesterol/high lipids, and various inflammatory diseases and conditions.
1 . A composition comprising
5-cholesten-3, 25-diol, 3-sulfate (25HC3S) or a pharmaceutically acceptable salt thereof; and
at least one cyclic oligosaccharide.
2 . The composition of claim 1 , wherein the cyclic oligosaccharide comprises a cyclodextrin or a cyclodextrin derivative.
3 . The composition of claim 2 , wherein the cyclodextrin or the cyclodextrin derivative comprises at least one of cyclodextrin, alkyl substituted cyclodextrin wherein the alkyl group comprises 1 to 8 carbons, hydroxyalkyl substituted cyclodextrin wherein the alkyl group comprises 1 to 8 carbons, sulfoalkyl ether substituted cyclodextrin wherein the alkyl group comprises 1 to 8 carbons, and alkyl ether substituted cyclodextrin wherein the alkyl group comprises 1 to 8 carbons.
4 . The composition of claim 2 , wherein the cyclodextrin or the cyclodextrin derivative comprises at least one of hydroxypropyl β-cyclodextrin, sulfobutyl ether β-cyclodextrin, α-cyclodextrin and γ-cyclodextrin.
5 . The composition of any of claims 1 to 4 , wherein the cyclic oligosaccharide is present in the composition at a concentration ranging from about 0.1% (w/w) to about 99% (w/w).
6 . The composition of any of claims 1 to 5 , wherein the cyclic oligosaccharide is present in the composition at a concentration ranging from about 0.1% (w/w) to about 90% (w/w).
7 . The composition of any of claims 1 to 6 , wherein the composition further comprises at least one alcohol.
8 . The composition of claim 7 , wherein the at least one alcohol comprises at least one diol.
9 . The composition of claim 8 , wherein the at least one diol comprises α-propylene glycol.
10 . The composition of any of claims 1 to 9 , wherein the composition comprises a physiologically acceptable carrier.
11 . The composition of claim 10 , wherein the physiologically acceptable carrier comprises at least one buffer.
12 . The composition of any of claims 1 to 11 , wherein the composition comprises at least one physiologically acceptable excipient.
13 . A method of treating, in a subject in need thereof, at least one of: hyperlipidemia or a disease or condition caused by hyperlipidemia; dysfunction or failure of at least one organ; a lipid metabolism disorder; metabolic disorder; atherosclerosis; injury caused by ischemia; unwanted cell death; sepsis; acute radiation syndrome; a liver disorder; a lipid accumulation disorder; and an inflammatory skin disease or skin lesion; the method comprising administering to the subject a therapeutically effective amount of the composition of any of claims 1 to 12 .
14 . The method of claim 13 , wherein the method comprises treating dysfunction or failure of at least one organ selected from kidney, liver, pancreas, heart, lung and brain.
15 . The method of claim 13 , wherein the method comprises treating dysfunction or failure of the liver caused by acetaminophen.
16 . The method of claim 13 , wherein the method comprises treating injury caused by ischemia.
17 . The method of claim 13 , wherein the method comprises treating injury caused by ischemia caused by ischemia/reperfusion injury.
18 . The method of claim 13 , wherein the method comprises treating a liver disorder.
19 . The method of claim 13 , wherein the method comprises treating a liver disorder that is non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
20 . The method of claim 13 , wherein the method comprises treating an inflammatory skin disease or skin lesion.
21 . The method of claim 13 , wherein the method comprises treating an inflammatory skin disease that is atopic dermatitis or psoriasis.
22 . A composition as defined in any one of claims 1 to 12 for use as a medicament.
23 . A composition as defined in any one of claims 1 to 12 for use in treatment of at least one disease or condition selected from hyperlipidemia or a disease or condition caused by hyperlipidemia; dysfunction or failure of at least one organ; a lipid metabolism disorder; metabolic disorder; atherosclerosis; injury caused by ischemia; unwanted cell death; sepsis; acute radiation syndrome; a liver disorder; a lipid accumulation disorder; and an inflammatory skin disease or skin lesion.
24 . Use of a composition as defined in any one of claims 1 to 12 in the manufacture of a medicament for use in treatment of at least one disease or condition selected from hyperlipidemia or a disease or condition caused by hyperlipidemia; dysfunction or failure of at least one organ; a lipid metabolism disorder; metabolic disorder; atherosclerosis; injury caused by ischemia; unwanted cell death; sepsis; acute radiation syndrome; a liver disorder; a lipid accumulation disorder; and an inflammatory skin disease or skin lesion.