Compositions comprising 5-cholesten-3, 25-diol, 3-sulfate (25hc3s) or pharmaceutically acceptable salt thereof and at least one cyclic oligosaccharide

Abstract

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.