Pharmaceutical Compositions Comprising a Hydroxyethylquercetin Glucuronide

Abstract

Disclosed herein are hydroxyethylquercetin glycosides, including compounds of Structural Formulas I, II, III and IV. The compounds disclosed are useful for inhibiting norepinephrine metabolism and treating antenatal and postnatal depression in subjects in need thereof.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising a hydroxyethylquercetin-O-glucuronide, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent, wherein the hydroxyethylquercetin-O-glucuronide is a trihydroxyethylquercetin-O-glucuronide. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the composition is formulated for oral administration. 
     
     
         3 . The pharmaceutical composition of  claim 1 , further comprising a second acid. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the second acid is citric acid or hydrochloric acid or a combination thereof 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the hydroxyethylquercetin-O-glucuronide is a hydroxyethylquercetin-3-O-glucuronide. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the hydroxyethylquercetin-O-glucuronide is a hydroxyethylquercetin-5-O-glucuronide. The pharmaceutical composition of  claim 1 , wherein the hydroxyethylquercetin-O-glucuronide is a hydroxyethylquercetin-7-O-glucuronide. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the hydroxyethylquercetin-O-glucuronide is a metabolite of troxerutin. 
     
     
         9 . A method of inhibiting norepinephrine metabolism in a subject in need thereof, comprising:
 administering to the subject an effective amount of the pharmaceutical composition of  claim 1 .   
     
     
         10 . The method of  claim 9 , wherein the administering is orally administering. 
     
     
         11 . The method of  claim 9 , further comprising administering an acidifier. 
     
     
         12 . The method of  claim 11 , wherein the acidifier is betaine, or a pharmaceutically acceptable salt thereof. 
     
     
         13 . The method of  claim 11 , wherein the acidifier is acidic liquid media. 
     
     
         14 . The method of  claim 13 , wherein the acidic liquid media has a pH of less than about 3. 
     
     
         15 . The method of  claim 13 , wherein the acidic liquid media comprises citric acid, acetic acid, or hydrochloric acid, or a combination of any of the foregoing. 
     
     
         16 . The method of  claim 13 , wherein the acidic liquid media comprises vinegar or a citrus juice, or a combination of the foregoing. 
     
     
         17 . A method of treating depression in a subject in need thereof, comprising administering to the subject an effective amount of a hydroxyethylquercetin-O-glucuronide, or a pharmaceutically acceptable salt thereof. 
     
     
         18 . The method of  claim 17 , wherein the subject is a human. 
     
     
         19 . A method of treating perinatal, antenatal or postpartum depression in a subject in need thereof, comprising administering to the subject an effective amount of a hydroxyethylquercetin-O-glucuronide, or a pharmaceutically acceptable salt thereof. 
     
     
         20 . The method of  claim 19 , wherein the subject is a pregnant, postnatal or postpartum woman.