Therapeutic methods and compositions involving isoflavones

Abstract

Therapeutic method of treatment, compositions and foodstuffs are described which contain isoflavone compounds described by general formula (I), in which Z is H, R 1 is H or R A CO wherein Ra is C 1-10 alkyl or an amino acid, R 2 is H, OH or OR B where R B is an amino acid, or COR A where R A is as previously defined, W is H, A is H or OH, and B is selected from (a), (b), (c) or W is H, and A and B taken together form a six-membered ring selected from (d), or W, A and B taken with the groups with which they are associated comprise (f) and B is (g) where R 3 is H, COR A where R A is as previously defined, CO 2 R C where R C is C 1-10 alkyl, or COR B where R B is as previously defined, R 4 is H, COR D where R D is H, OH, C 1-10 alkyl or an amino acid, CO 2 R C where R C is as previously defined, COR E where R E is H, C 1-10 alkyl or an amino acid, COOH, COR C where R C is as previously defined, or CONHR E where R E is as previously defined, R 5 is H, CO 2 R C where R C is as previously defined, or COR C OR E where R C and R E are as previously defined, and where the two R 5 groups are attached to the same group they are the same or different, R 6 is H or hydroxyl C 1-10 alkyl, X is preferably O, but may be N or S, and Y is (h) where R 7 is H, or C 1-10 alkyl.

1 . A method for the treatment or prophylaxis, amelioration, defence against, and/or prevention of menopausal syndrome including hot flushes, anxiety and depression, mood swings, night sweats, headaches, and urinary incontinence; osteoporosis; premenstrual syndrome including fluid retention and cyclical mastalgia, and dysmenorrhoea; Reynaud's Syndrome; Reynaud's Phenomenon; Buergers Disease; coronary artery spasm; migraine headaches; hypertension; benign prostatic hypertrophy; breast cancer; uterine cancer; ovarian cancer; testicular cancer; large bowel cancer; endometrial cancer; prostatic cancer; uterine cancer; atherosclerosis; Alzheimers disease; inflammatory diseases including inflammatory bowel disease, ulcerative colitis, and Crohns disease; rheumatic diseases including rheumatoid arthritis; acne; baldness including male pattern baldness (alopecia hereditaria); psoriasis and/or diseases associated with oxidant stress including cancer, myocardial infarction stroke, arthritis sunlight induced skin damage or cataracts; which comprises administering to a subject a therapeutically effective amount of one or more compounds of the formula I: 
       
         
           
           
               
               
           
         
         in which 
         Z is H, 
         R 1  is H, or R A CO where R A  is C 1-10  alkyl or an amino acid, 
         R 2  is H, OH, or OR B  where R B  is an amino acid or COR A  where R A  is as previously defined, 
         W is H, A is H or OH, and B is selected from 
       
       
         
           
           
               
               
           
         
         W is H, and A and B taken together form a six membered ring selected from 
       
       
         
           
           
               
               
           
         
         W, A and B taken with the groups with which they are associated comprise 
       
       
         
           
           
               
               
           
         
         W and A taken together with the groups with which they are associated comprise 
       
       
         
           
           
               
               
           
         
         and B is 
       
       
         
           
           
               
               
           
         
         wherein 
         R 3  is H, COR A  where R A  is as previously defined, CO 2 R C  where R C  is C 1-10  alkyl, or 
         COR B  where R B  is as previously defined, 
         R 4  is H, COR D  where R D  is H, OH, C 1-10  alkyl or an amino acid, CO 2 R C  where R C  is as previously defined, COR E  where R E  is H, C 1-10  alkyl or an amino acid, COOH, COR C  where R C  is as previously defined, or CONHR E  where R E  is as previously defined, 
         R 5  is H, CO 2 R C  where R C  is as previously defined, or 
         COR C OR E  where R C  and R E  are as previously defined, and where the two R 5  groups are attached to the same group they are the same or different, 
         R 6  is H or hydroxy C 1-10  alkyl, 
         X is preferably O, but may be N or S, and 
         Y is 
       
       
         
           
           
               
               
           
         
         where R 7  is H, or C 1-10  alkyl 
         provided that compounds of the formula I where 
         R 1 , W and Z are H 
         R 2  is H or OH 
         A and B taken together are a six membered ring 
       
       
         
           
           
               
               
           
         
         Y is as defined above 
         and R 7  is H or OCH 3 , 
         are specifically excluded, and 
         provided that where the method is a method for the treatment or prophylaxis of menopausal syndrome or premenstrual tension syndrome compounds of the formula I where 
         R 1  is H, W and Z are H, and R 2  is H or OH, 
         A and B taken together are a six membered ring 
       
       
         
           
           
               
               
           
         
         or A is OH and B is 
       
       
         
           
           
               
               
           
         
         where Y is as defined above and R 7  is H are specifically excluded, and further provided that where the method is a method for the treatment of a form of cancer or rheumatoid arthritis compounds of the formula I where: 
         R 1  and W are H, Z is H or OCH 3  and R 2  is H or OH, and 
         A and B taken together are a six membered ring of the formula 
       
       
         
           
           
               
               
           
         
         Y is as defined above, R 4  is CO 2 H or CO 2 CH 2 CH 3 , and R 7  is H are specifically excluded. 
       
     
     
         2 . A method according to  claim 1  wherein said compounds of the formula I are selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein 
         R 8  is COR where R D  is as previously defined, 
         R 9 CO 2 R C  or COR E  where R C  and R E  are as previously defined, 
         R 10  is COR C  or COR C OR E  where R C  and R E  are as previously defined, 
         R 11  is H or OH, 
         R 12  is H, COOH, CO 2 R C  where R C  and is as previously defined, or CONHR E  where R E  is as previously defined, 
         R 13  is OH, OR B  where R B  is as previously defined, or COR A  where R A  is as previously defined, 
         R 14  is H, or COR A  where R A  is as previously defined, 
         R 15  is COR A  where R A  is as previously defined, 
         R 16  is H, COR B  or CO 2 R C  where R B  and R C  are as previously defined, 
         R 17  is H or hydroxy C 1-10  alkyl, 
         R 18  is H or C 1-10  alkyl, 
         and   represents either a single bond or a double bond. 
       
     
     
         3 . A method according to  claim 2  which is a method for the treatment of menopausal syndrome, hypertension, atherosclerosis, male impotence, premenstrual syndrome, or cyclical mastalgia wherein one or more compounds of the formulae 1, 3, 8, 10, 11, 13 or 14 are administered to a subject in need of such treatment in association with a pharmaceutically acceptable carrier or excipient. 
     
     
         4 . A method according to  claim 2  which is a method for the treatment of breast, ovarian, testicular, uterine, large bowel, leukemia, endometrial, or prostatic cancer wherein one or more compounds of the formulae 1, 8, 10, 11, 13 or 14 are administered to a subject in need of such treatment in association with a pharmaceutically acceptable carrier or excipient. 
     
     
         5 . A method according to  claim 2  which is a method for the treatment of cancer, myocardial infarction, stroke, arthritis or cataracts which comprises administering to a subject in need of such treatment one or more compounds of the formulae 1, 3, 8, 10, 13 and 14 in association with a pharmaceutically acceptable carrier and/or excipient. 
     
     
         6 . Use of the compounds of the formula I for the manufacture of a medicament for the treatment, amelioration, defence against prophylaxis and/or prevention of one or more of the therapeutic indications set forth in  claim 1 . 
     
     
         7 . Use according to  claim 6  wherein said compounds of the formula I are selected from compounds 1 to 19 as defined in  claim 2 . 
     
     
         8 . Use of a compound of the formula I in the treatment, amelioration defence against, prophylaxis and/or prevention of one or more of the therapeutic indications set forth in  claim 1 . 
     
     
         9 . Use according to  claim 8  wherein said compounds of the formula I are selected from compounds 1 to 19 as defined in  claim 2 . 
     
     
         10 . An agent for the treatment, prophylaxis, amelioration, defense against and/or treatment of one or more of the therapeutic indications set forth in  claim 1 , which comprises a compound of the formula I as defined in  claim 1 , optionally in association with one or more pharmaceutically acceptable carriers and/or excipients. 
     
     
         11 . An agent according to  claim 10  wherein said compounds of the formula I are selected from compounds 1 to 19 as defined in  claim 2 . 
     
     
         12 . A composition which comprises one or more compounds of the formula I as defined in  claim 1  or  2  in association with one or more pharmaceutically carriers and/or excipients. 
     
     
         13 . An antioxidant composition which comprises one or more compounds of the formula I as defined in  claims 1  or  2  in association with one or more physiologically and/or cosmetically acceptable carriers and/or excipients. 
     
     
         14 . An antioxidant composition which comprises one or more compounds of the formula I as defined in  claim 1 , and vitamin E, optionally in association with a pharmaceutically acceptable carrier and or excipient. 
     
     
         15 . An antioxidant composition according to  claim 14  wherein said one or more compounds of the formula I comprise one or more compounds of the formulae 1 to 19 as defined in  claim 2 . 
     
     
         16 . A composition according to  claim 13  which comprises a skin cream or gel which contains one or more of compounds 1 to 19 as defined in  claim 2 . 
     
     
         17 . A composition according to  claim 13  which comprises a solid dosage unit composition comprising one or more compounds of compounds 1 to 19 as defined in  claim 2 . 
     
     
         18 . A composition according to  claim 12  wherein said compounds of the formula I are selected from compounds 1 to 19 as defined in  claim 2 . 
     
     
         19 . A food stuff or drink which contains one or more compounds of the formula I as defined in  claim 1 . 
     
     
         20 . A food stuff or drink according to  claim 19  wherein said compounds of the formula I are selected from compounds 1 to 19 as defined in  claim 2 . 
     
     
         21 . A microbial culture or a food stuff containing one or more microbial strains, which microorganisms produce one or more compounds of the formula I as defined in  claim 1 . 
     
     
         22 . A microbial culture according to  claim 21  wherein said compounds of the formula I are selected from compounds 1 to 19 as defined in  claim 2 . 
     
     
         23 . A microorganism which produces one or more compounds of the formula I, or a mixture of microorganisms which produce one or more compounds of the formula I. 
     
     
         24 . A microorganism according to  claim 23  wherein said compounds of the formula I are selected from compounds 1 to 19 as defined in  claim 2 .