Method for modulating steroidogenic activity

Abstract

The present invention relates generally to a method for modulating steroidogenic activity and a composition useful for same. The present invention further relates to a composition comprising a steroidogenic modulator useful for modulating physiological processes mediated by the androgen receptor or an active form thereof or complex comprising same and/or for modulating physiological processes mediated by estrogen receptors. The composition of the present invention preferably comprises an extract of herbs or botanical or horticultural equivalents of the herbs or chemical or functional equivalents of one or more components of the herbal extract thereof.

1 . A composition comprising a preparation of  Eucommia ulmoides  or of a horticultural equivalent of  Eucommia ulmoides  prepared by alcohol or water extraction thereof and chromatography a) over a hydroxypropylated, cross-linked dextran matrix having an exclusion limit for peptides of 4 kilodaltons and an exclusion limit for small organic molecules of 5 kilodaltons with elution using n-butanol or b) over a reverse phase matrix with elution by an aqueous buffer and acetonitrile gradient or c) over a diol matrix with elution using at least one organic solvent; 
 that lacks fluorescent components exhibiting R f  values of 0 and 0.4 and also lacks vanillin-sulphuric acid reactive components exhibiting R f  values 0.47,0.62, 0.71 and I when the composition is separated by two dimensional thin layer chromatography on silica gel and eluted in the first dimension with dichloromethane and in the second dimension with hexane.    
     
     
         2 . A method of modulating a steroid-mediated physiological condition in a subject comprising administering to said subject an amount of a formulation of the composition of  claim 1  that is effective for modulating the steroid-mediated physiological condition in the subject.  
     
     
         3 . The method according to  claim 2  wherein the preparation is administered to a human, a primate or a livestock animal.  
     
     
         4 . The method according to  claim 2  wherein the steroid-mediated physiological condition is mediated by an androgen or by androgen receptor.  
     
     
         5 . The method according to  claim 2 , wherein the steroid-mediated physiological condition is male sexual development, secondary sexual development, anabolic processes, male sex drive, skin condition, hair growth, physical stamina or lipid metabolism.  
     
     
         6 . The method according to  claim 2  wherein the steroid-mediated physiological condition is mediated by estrogen or estrogen receptor.  
     
     
         7 . The method according to  claim 2 , wherein the steroid-mediated condition is menopause, osteoporosis, cardiovascular disease or other estrogen-related disease or process.  
     
     
         8 . The method according to  claim 2  wherein the formulation comprises a purified or chemically synthesized form of a component of an alcohol or water preparation of  Eucommia ulmoides.    
     
     
         9 . A method for producing a steroidogenic preparation from  Eucommia ulmoides  comprising: 
 i) optionally macerating  Eucommia ulmoides  plants or at least one part thereof;    ii) obtaining a solvent preparation by soaking the  Eucommia ulmoides  plants or parts thereof in a solvent system;    iii) separating the solvent preparation from insoluble materials;    iv) obtaining an preparation residue by drying the solvent preparation;    v) dry packing the preparation residue on a diol column; and    vi) obtaining an eluate comprising steroidogenic compounds from the column by eluting using at least one of hexane, hexane:dichloromethane 1:1, dichloromethane, ethyl acetate, or a C 1  to C 6  alkane alcohol;    thereby obtaining a steroidogenic preparation.    
     
     
         10 . The method of  claim 9 , further comprising: 
 iiia) precipitating undesired compounds by adding water in an amount of up to 20% v/v; and    iiib) separating the solvent preparation from the precipitate; prior to step iv).    
     
     
         11 . The method of  claim 10 , wherein the C 1  to C 6  alkane alcohol is ethanol or methanol.  
     
     
         12 . The method of  claim 10 , wherein the diol column is eluted with a first solvent that is hexane, hexane:dichloromethane 1:1, dichloromethane, ethyl acetate, or a C 1  to C 6  alkane alcohol and then is eluted with a different solvent that is hexane, hexane:dichloromethane 1:1, dichloromethane, ethyl acetate, or a C 1  to C 6  alkane alcohol.  
     
     
         13 . A method for producing a steroidogenic preparation from  Eucommia ulmoides  comprising: 
 i) optionally macerating  Eucommia ulmoides  plants or at least one part thereof;    ii) obtaining a solvent preparation by soaking the  Eucommia ulmoides  plants or parts thereof in a solvent system;    iii) separating the solvent preparation from insoluble materials;    iv) applying the preparation to a reverse phase chromatography column and eluting the steroidogenic compounds with a mobile phase comprising water and acetonitrile in an amount that varies over time from 10% to 100% acetonitrile; thereby obtaining a steroidogenic preparation.    
     
     
         14 . The method of  claim 13 , further comprising: 
 iiia) precipitating undesired compounds from the solvent preparation by adding water in an amount of up to 20% v/v; and    iiib) separating the solvent preparation from the precipitate; prior to step iv).    
     
     
         15 . A method for producing a steroidogenic preparation from  Eucommia ulmoides  comprising: 
 i) optionally macerating  Eucommia ulmoides  plants or at least one part thereof;    ii) obtaining a solvent preparation by soaking the  Eucommia ulmoides  plants or parts thereof in a solvent system;    iii) separating the solvent preparation from insoluble materials;    iv) applying the preparation to a chromatography matrix comprising dextran crosslinked by an alkyl ether and eluting the steroidogenic compounds with a C 1 -C 6  alcohol;    thereby obtaining a steroidogenic preparation.    
     
     
         16 . The method of  claim 15 , further comprising 
 iiia) precipitating undesired compounds from the solvent preparation by adding water in an amount of up to 20% v/v; and    iiib) separating the solvent preparation from the precipitate; prior to step iv).    
     
     
         17 . A composition comprising the preparation produced by the method of any one of claims  9 ,  13  or  15 .  
     
     
         18 . A composition comprising a portion of the preparation produced by the method of  claim 13 , that elutes at any one of: 
 i) 100% acetonitile; or    ii) a gradient of 50% to 100% acetonitrile.    
     
     
         19 . A composition comprising a combination of the eluates obtained by the method of  claim 12 .  
     
     
         20 . An article of manufacturing a composition according to  claim 1  and written material that provides instructions or urges the use of the composition to modulate, a physiological condition or response mediated by a steroid.