Icariside compound, preparation method thereof, and application thereof

Abstract

An icariside compound as shown in Formula I wherein the compound is a natural chemical component in the traditional Chinese herbal epimedium or a chemically modified or a totally synthetic product based on the natural component. The compound can be used for preparing pharmaceuticals, health care products, cosmetic and skin care products and the like for improvement of immunity in a human body.

What is claimed is: 
     
         1 . Icariside compounds as shown in Formula I: 
       
         
           
           
               
               
           
         
         Icariside compounds 
         (Icariside derivatives) 
       
       wherein the groups represented by R 1 , R 2 , and R 3  in formula I are defined as follows: 
       (1) R 1  is selected from H, OH, OCH 3 , CH 3 COO, CH 3 , CF 3 , NH 2 , CH 3 NH, CH 3 CONH, CN, Br, Cl, F; 
       (2) R 2  is selected from H, OH, OCH 3 , CH 3 COO, NH 2 , CH 3 NH, (CH 3 ) 2 N, CH 3 CONH, CN; 
       (3) R 3  is selected from H, OH, OCH 3 , OC 2 H 5 , OC 3 H 7 , CH 3 COO, CH 3 , CF 3 , C 1 -C 6 —NH 2  (wherein C 1 -C 6  is an alkyl group, a cycloalkyl group, an olefin group, cyclic olefin group, in particular a cyclopentylamino group, a cyclohexylamino; and a morpholinyl group, a methylpiperazinyl having 1 to 6 carbon atoms), NH 2 , CH 3 NH, (CH 3 ) 2 N, (CH 3 CH 2 ) 2 N, CH 3 CONH, CN, Br, Cl, F, amino acid acyl, amino acid acylamino (R′—CH—CONH—), oligopeptideacyl, oligopeptide amido group. 
     
     
         2 . The icariside compounds of Formula I according to  claim 1 , wherein R 1 =OH, OCH 3 ; R 2 =OH, OCH 3 ; R 3 =OH, OCH 3 , OC 3 H 7 . 
     
     
         3 . The icariside compounds of Formula I according to  claim 1 , wherein the compound is:
 (1) R 1 =OH, R 2 =OH, R 3 =OH;   (2) R 1 =OH, R 2 =OH, R 3 =OCH 3 ;   (3) R 1 =OH or OCH 3 , R 2 =OH or OCH 3 , R 3 =OH, OCH 3 , OC 3 H 7 ;   (4) R 1 =OCH 3 , R 2 =OH, R 3 =OCH 3 ;   (5) R 1 =OH, R 2 =OCH 3 , R 3 =OCH 3 ;   (6) R 1 =OH, R 2 =OH, R 3 =OC 3 H 7 .   
     
     
         4 . A method for preparation of any icariside compound of Formula I, wherein 
       
         
           
           
               
               
           
         
         Icariside compounds
 (Icariside derivatives) 
 
       
       wherein the groups represented by R 1 , R 2 , and R 3  in formula I are defined as follows: 
       (1) R 1  is selected from H, OH, OCH 3 , CH 3 COO, CH 3 , CF 3 , NH 2 , CH 3 NH, CH 3 CONH, CN, Br, Cl, F; 
       (2) R 2  is selected from H, OH, OCH 3 , CH 3 COO, NH 2 , CH 3 NH, (CH 3 ) 2 N, CH 3 CONH, CN; 
       (3) R 3  is selected from H, OH, OCH 3 , OC 2 H 5 , OC 3 H 7 , CH 3 COO, CH 3 , CF 3 , C 1 -C 6 —NH 2  (wherein C 1 -C 6  is an alkyl group, a cycloalkyl group, an olefin group, cyclic olefin group, in particular a cyclopentylamino group, a cyclohexylamino; and a morpholinyl group, a methylpiperazinyl having 1 to 6 carbon atoms), NH 2 , CH 3 NH, (CH 3 NH, (CH 3 ) 2 N, (CH 3 CH 2 ) 2 N, CH 3 CONH, CN, Br, Cl, F, amino acid acyl, amino acid acylamino (R′—CH—CONH—), oligopeptideacyl, oligopeptide amido group, and so on, 
       said method comprising the step of obtaining icariside compounds of formula I by derivatization of a natural product including but not limited to icariside I or icariside C. 
     
     
         5 . A method according to  claim 4 , comprising the step of converting an abundant component icariin in epimedium to icariside I by enzyme conversion. 
     
     
         6 . A method according to  claim 5 , further comprising the step of using icariin as raw material and dissolving it in a phosphate buffer followed by adding immobilized rhamnosidase thereto for reaction and performing recrystallization. 
     
     
         7 . A method according to  claim 5 , further comprising the step of using epimedoside A as raw material and adding immobilized rhamnosidase for reaction to remove 3-O-rhamnosyl group from epimedoside A molecule to obtain icariside C. 
     
     
         8 . A composition, comprising at least one of the icariside compounds of Formula I, for example icariside I or icariside C, and at least one of a pharmaceutically acceptable or health care acceptable or cosmetic or skin care acceptable carrier and/or adjuvant. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . A composition according to  claim 8  which may be in the form of tablets, pills, capsules, injections, suspensions, emulsions, liniments for external use or mask. 
     
     
         12 . A process for treating human immunity-related diseases, particularly in treatment of diseases by improving human immunity by promoting human cells to produce γ-interference (interferon-gamma, IFN-γ), particularly for treating any TH1 immune response (induction of cellular immune response) related diseases, and more particularly for treating diseases including tuberculosis, influenza, hepatitis B and C and other infective diseases, and cancer, comprising the step of using a pharmaceutical composed of icariside compounds as shown in Formula I: 
       
         
           
           
               
               
           
         
         Icariside compounds 
         (Icariside derivatives) 
       
       wherein the groups represented by R 1 , R 2 , and R 3  in formula I are defined as follows: 
       (1) R 1  is selected from H, OH, OCH 3 , CH 3 COO, CH 3 , CF 3 , NH 2 , CH 3 NH, CH 3 CONH, CN, Br, Cl, F; 
       (2) R 2  is selected from H, OH, OCH 3 , CH 3 COO, NH 2 , CH 3 NH, (CH 3 ) 2 N, CH 3 CONH, CN; 
       (3) R 3  is selected from H, OH, OCH 3 , OC 2 H 5 , OC 3 H 7 , CH 3 COO, CH 3 , CF 3 , C 1 -C 6 —NH 2  (wherein C 1 -C 6  is an alkyl group, a cycloalkyl group, an olefin group, cyclic olefin group, in particular a cyclopentylamino group, a cyclohexylamino; and a morpholinyl group, a methylpiperazinyl having 1 to 6 carbon atoms), NH 2 , CH 3 NH, (CH 3 ) 2 N, (CH 3 CH 2 ) 2 N, CH 3 CONH, CN, Br, Cl, F, amino acid acyl, amino acid acylamino (R′—CH—CONH—), oligopeptideacyl, oligopeptide amido group, and so on. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled)