Compositions and methods for treating hypercholesterolemia using ortanique peel extract

Abstract

The invention relates to compositions and methods for treating hypercholesterolemia, including methods for increasing HDL cholesterol levels, using a composition comprising an extract from the Ortanique peel. The invention also relates to compositions and methods for treating hypercholesterolemia, including methods for increasing HDL cholesterol levels, using a composition comprising substantially similar amounts of tetramethylscutellarein and nobiletin by weight and/or a composition comprising substantially similar amounts of tetramethylscutellarein, nobiletin, and tangeretin by weight.

1 . A method for reducing LDL cholesterol level in a subject comprising administering to a subject in need thereof an effective amount of a composition comprising a polar solvent soluble extract from Ortanique peel, wherein the reduction of LDL cholesterol level is observed relative to the subject before administration of the composition. 
   
   
       2 . The method of  claim 1 , wherein the polar solvent is methanol. 
   
   
       3 . The method of  claim 1 , wherein administration of the composition to the subject also results in an increase in HDL cholesterol level in the subject relative to the subject before administration of the composition. 
   
   
       4 . The method of  claim 1 , wherein the subject is a human. 
   
   
       5 . The method of  claim 1 , wherein the composition is suitable for oral administration. 
   
   
       6 . The method of  claim 1 , wherein the extract comprises at least about 60% polymethoxylated flavones by weight. 
   
   
       7 . The method of  claim 1 , wherein the extract comprises six different polymethoxylated flavones. 
   
   
       8 . The method of  claim 7 , wherein the six polymethoxlylated flavones are nobiletin, sinensetin, tangeretin, heptamethoxyflavone, hexamethyl-o-quercetagetin, and tetramethylscutellarein. 
   
   
       9 . The method of  claim 7 , wherein the extract comprises about 15-21% nobiletin, about 14.5-20.5% tetramethylscutellarein, about 4-10% sinensetin, about 13-19% tangeretin, about 0.3-2.3% hexamethyl-o-quercetagetin, and about 0.5-3.5% heptamethoxyflavone by weight. 
   
   
       10 . The method of  claim 9 , wherein the extract comprises about 18% nobiletin, about 17.5% tetramethylscutellarein, about 7% sinensetin, about 16% tangeretin, about 1.3% hexamethyl-o-quercetagetin, and about 2% heptamethoxyflavone by weight. 
   
   
       11 . A method for increasing HDL cholesterol level in a subject comprising administering to a subject in need thereof an effective amount of a composition comprising a polar solvent soluble extract from Ortanique peel, wherein the increase of HDL cholesterol level is observed relative to the subject before administration of the composition. 
   
   
       12 . The method of  claim 11 , wherein the polar solvent is methanol. 
   
   
       13 . The method of  claim 11 , wherein the composition is suitable for oral administration. 
   
   
       14 . The method of  claim 11 , wherein the extract comprises at least about 60% polymethoxylated flavones by weight. 
   
   
       15 . The method of  claim 11 , wherein the extract comprises six different polymethoxylated flavones. 
   
   
       16 . The method of  claim 15 , wherein the six polymethoxlylated flavones are nobiletin, sinensetin, tangeretin, heptamethoxyflavone, hexamethyl-o-quercetagetin, and tetramethylscutellarein. 
   
   
       17 . The method of  claim 16 , wherein the extract comprises about 15-21 % nobiletin, about 14.5-20.5% tetramethylscutellarein, about 4-10% sinensetin, about 13-19% tangeretin, about 0.3-2.3% hexamethyl-o-quercetagetin, and about 0.5-3.5% heptamethoxyflavone by weight. 
   
   
       18 . The method of  claim 17 , wherein the extract comprises about 18% nobiletin, about 17.5% tetramethylscutellarein, about 7% sinensetin, about 16% tangeretin, about 1.3% hexamethyl-o-quercetagetin, and about 2% heptamethoxyflavone by weight. 
   
   
       19 . A method for reducing total cholesterol level in a subject comprising administering to a subject in need thereof an effective amount of a composition comprising a polar solvent soluble extract from Ortanique peel, wherein the reduction of total cholesterol level is observed relative to the subject before administration of the composition. 
   
   
       20 . The method of  claim 19 , wherein the polar solvent is methanol. 
   
   
       21 . The method of  claim 19 , wherein the composition is suitable for oral administration. 
   
   
       22 . The method of  claim 19 , wherein the extract comprises at least 60% polymethoxylated flavones by weight. 
   
   
       23 . The method of  claim 19 , wherein the extract comprises six different polymethoxylated flavones. 
   
   
       24 . The method of  claim 23 , wherein the six polymethoxlylated flavones are nobiletin, sinensetin, tangeretin, heptamethoxyflavone, hexamethyl-o-quercetagetin, and tetramethylscutellarein. 
   
   
       25 . The method of  claim 24 , wherein the extract comprises about 15-21 % nobiletin, about 14.5-20.5% tetramethylscutellarein, about 4-10% sinensetin, about 13-19% tangeretin, about 0.3-2.3% hexamethyl-o-quercetagetin, and about 0.5-3.5% heptamethoxyflavone by weight. 
   
   
       26 . The method of  claim 25 , wherein the extract comprises about 18% nobiletin, about 17.5% tetramethylscutellarein, about 7% sinensetin, about 16% tangeretin, about 1.3% hexamethyl-o-quercetagetin, and about 2% heptamethoxyflavone by weight. 
   
   
       27 . A method for reducing triglyceride levels in a subject comprising administering to a subject in need thereof an effective amount of a composition comprising a polar solvent soluble extract from Ortanique peel, wherein the reduction of triglyceride levels is observed relative to the subject before administration of the composition. 
   
   
       28 . The method of  claim 27 , wherein the polar solvent is methanol. 
   
   
       29 . The method of  claim 27 , wherein the composition is suitable for oral administration. 
   
   
       30 . The method of  claim 27 , wherein the extract comprises at least about 60% polymethoxylated flavones by weight. 
   
   
       31 . The method of  claim 27 , wherein the extract comprises six different polymethoxylated flavones. 
   
   
       32 . The method of  claim 31 , wherein the six polymethoxlylated flavones are nobiletin, sinensetin, tangeretin, heptamethoxyflavone, hexamethyl-o-quercetagetin, and tetramethylscutellarein. 
   
   
       33 . The method of  claim 32 , wherein the extract comprises about 15-21% nobiletin, about 14.5-20.5% tetramethylscutellarein, about 4-10% sinensetin, about 13-19% tangeretin, about 0.3-2.3% hexamethyl-o-quercetagetin, and about 0.5-3.5% heptamethoxyflavone by weight. 
   
   
       34 . The method of  claim 33 , wherein the extract comprises about 18% nobiletin, about 17.5% tetramethylscutellarein, about 7% sinensetin, about 16% tangeretin, about 1.3% hexamethyl-o-quercetagetin, and about 2% heptamethoxyflavone by weight. 
   
   
       35 . A method for reducing LDL cholesterol level in a subject comprising administering to a subject in need thereof an effective amount of a composition comprising substantially similar amounts of tetramethylscutellarein and nobiletin by weight, wherein the reduction of total cholesterol level is observed relative to the subject before administration of the composition. 
   
   
       36 . The method of  claim 35 , wherein the composition comprises about 16-19% tetramethylscutellarein and about 16-19% nobiletin by weight. 
   
   
       37 . The method of  claim 35 , wherein the composition comprises about 17.5% tetramethylscutellarein and about 18% nobiletin by weight. 
   
   
       38 . The method of  claim 35 , wherein administration of the composition to the subject also results in an increase in HDL cholesterol level in the subject relative to the subject before administration of the composition. 
   
   
       39 . The method of  claim 35 , wherein administration of the composition to the subject also results in a decrease in total cholesterol level in the subject relative to the subject before administration of the composition. 
   
   
       40 . A composition comprising substantially similar amounts of tetramethylscutellarein and nobiletin by weight, wherein the combined amount of tetramethylscutellarein and nobiletin is less than about 60% of the composition by weight. 
   
   
       41 . The composition of  claim 40 , comprising about 14-21% of each of tetramethylscutellarein and nobiletin by weight. 
   
   
       42 . A composition of  claim 40 , further comprising sinensetin, tangeretin, heptamethoxyflavone, and hexamethyl-o-quercetagetin. 
   
   
       43 . The composition of  claim 42 , comprising about 15-21% nobiletin, about 14.5-20.5% tetramethylscutellarein, about 4-10% sinensetin, about 13-19% tangeretin, about 0.3-2.3% hexamethyl-o-quercetagetin, and about 0.5-3.5% heptamethoxyflavone by weight. 
   
   
       44 . The composition of  claim 43 , comprising about 18% nobiletin, about 17.5% tetramethylscutellarein, about 7% sinensetin, about 16% tangeretin, about 1.3% hexamethyl-o-quercetagetin, and about 2% heptamethoxyflavone by weight. 
   
   
       45 . A composition of  claim 40 , comprising substantially similar amounts of tetramethylscutellarein, nobiletin and tangeretin by weight, wherein the combined amount of tetramethylscutellarein, nobiletin and tangeretin is less than about 60% of the composition by weight. 
   
   
       46 . A pharmaceutical formulation comprising: (a) a pharmaceutically acceptable carrier or vehicle; and (b) an effective amount of the composition of any one of  claims 41 - 45 . 
   
   
       47 . A pharmaceutical formulation comprising: (a) a pharmaceutically acceptable carrier or vehicle; and (b) an effective amount of a polar solvent soluble extract from Ortanique peel. 
   
   
       48 . The pharmaceutical formulation of  claim 47 , wherein the extract is methanol soluble.