Phytoestrogen product of red clover and pharmaceutical uses thereof

Abstract

The present invention provides compositions comprising optimized ratios of Red clover phytoestrogens as determined by a proprietary physiologically based pharmacokinetic and pharmacodynamic model. The compositions are useful for modulating, preventing or treating postmenopausal or climacteric symptoms, which include but are not limited to bone loss, bone remodeling, hot flushes and vaginal atrophy. The present invention also provides methods for modulating, preventing or treating postmenopausal or climacteric symptoms using the compositions disclosed herein.

1 - 28 . (canceled) 
     
     
         29 . A method of alleviating, preventing or treating one or more postmenopausal or climacteric symptoms in a subject, comprising the step of administering to the subject in need thereof an effective amount of a composition comprising Biochanin A, genistein, formononetin and daidzein, wherein the composition comprises 80%-96% Biochanin A, 1%-12% genistein, 1%-5% formononetin and 1%-5% of daidzein, wherein the effective amount includes 1.0-6.0 mg of total isoflavones, and the composition is administered via a route to avoid first-pass gastrointestinal and hepatic effects, and to avoid colonic bacterial metabolism, wherein the postmenopausal or climacteric symptoms are selected from the group consisting of:
 a. hot flashes;   b. vaginal atrophy;   c. vaginal dryness;   d. diaphoresis;   e. night sweat;   f. urinary tract symptoms;   g. sleep disturbance;   h. osteoporosis; and   i. mood swings.   
     
     
         30 . The method of  claim 29 , wherein the composition includes 5 mg of Biochanin A, 0.104 mg of genistein, 0.087 mg of formononetin, and 0.071 mg of daidzein. 
     
     
         31 . The method of  claim 29 , wherein the composition includes a ratio of Biochanin A to genistein is about 48:1. 
     
     
         32 . The method of  claim 29 , wherein the composition includes a ratio of Biochanin A to formononetin is about 58:1. 
     
     
         33 . The method of  claim 29 , wherein the composition includes a ratio of Biochanin A to daidzein is about 70:1. 
     
     
         34 . The method of  claim 29 , wherein the composition is formulated as parenteral, buccal, sublingual, topical, transdermal or intra-vaginal dosage forms. 
     
     
         35 . The method of  claim 29 , wherein the composition is formulated as a dosage form for intramuscular, subcutaneous or intravenous administration. 
     
     
         36 . The method of  claim 29 , wherein the composition is formulated in the form of suppository, cream, injection, solution, or suspension. 
     
     
         37 . A pharmaceutical composition for alleviating, preventing or treating one or more postmenopausal or climacteric symptoms in a subject, comprising 1-6 mg of total isoflavones comprising 80%-96% Biochanin A, 1%-12% genistein, 1%-5% formononetin and 1%-5% of daidzein, wherein said isoflavones are aglycone forms, the composition is configured to be administered via a route to avoid first-pass gastrointestinal and hepatic effects, and to avoid colonic bacterial metabolism, wherein the postmenopausal or climacteric symptoms are selected from the group consisting of: a. hot flashes; b. vaginal atrophy; c. vaginal dryness; d. diapioresis; e. night sweat; f. urinary tract symptoms; g. sleep disturbance; h. osteoporosis; and i. mood swings. 
     
     
         38 . The pharmaceutical composition of  claim 37 , comprising 5 mg of Biochanin A, 0.104 mg of genistein, 0.087 mg of formononetin, and 0.071 mg of daidzein. 
     
     
         39 . The pharmaceutical composition of  claim 37 , wherein the weight ratio of Biochanin A to genistein is about 48:1. 
     
     
         40 . The pharmaceutical composition of  claim 37 , wherein the weight ratio of Biochanin A to formononetin is about 58:1. 
     
     
         41 . The pharmaceutical composition of  claim 37 , wherein the weight ratio of Biochanin A to daidzein is about 70:1. 
     
     
         42 . The pharmaceutical composition of  claim 37 , formulated as a dosage form for parenteral, buccal, sublingual, topical, transdermal or intra-vaginal administration. 
     
     
         43 . The pharmaceutical composition of  claim 37 , formulated as a dosage form for intramuscular, subcutaneous or intravenous administration. 
     
     
         44 . The pharmaceutical composition of  claim 37 , formulatedin the form of a suppository, cream, injection, solution, or suspension.