Active fraction of a polar solvent extract from the latex of euphorbiaceae plants

Abstract

The present invention generally refers to an active fraction of an extract of the latex of plants from the family Euphorbiaceae in a polar solvent, as well as of one or more compounds contained therein, as well as the use of said fraction and/or said compounds, particularly in the treatment of cancer. The invention also refers to compositions comprising said active fraction and/or said compounds, as well as their use for the treatment of diseases concerning cell proliferation/angiogenesis, particularly cancer.

1 . Active fraction of a polar solvent extract of an Euphorbiaceae plant latex characterized by the fact that it comprises, among eight fractions obtained in separation by chromatography column, the heavier fractions 6, 7 and 8. 
   
   
       2 . The fraction of  claim 1 , characterized by the fact that it only comprises fraction 7. 
   
   
       3 . The fraction of  claim 1 , characterized by the fact that said latex is preferably fresh. 
   
   
       4 . The fraction of  claim 1 , characterized by the fact that said polar solvent has a dipole moment between about 1.60 and about 1.80 and dielectric constant between about 15 and about 18. 
   
   
       5 . The fraction of  claim 4 , characterized by the fact that said polar solvent is an alcohol. 
   
   
       6 . The fraction of  claim 4 , characterized by the fact that said solvent is n-butanol. 
   
   
       7 . The fraction of  claim 1 , characterized by the fact that the Euphorbiaceae plant is from the genus  Euphorbia.    
   
   
       8 . The fraction of  claim 7 , characterized by the fact that the plant is  Euphorbia tirucalli L.    
   
   
       9 . The fraction of any of  claims 1  to  8 , characterized by the fact that it contains molecules with molecular weight between about 500 and about 600. 
   
   
       10 . The fraction of any of  claims 1  to  8 , characterized by the fact that it contains one or more of the compounds 3-(2,4,6-dodecatrienoyl)-ingenol and 3-(2,4,6,8-tetradecatetranoyl)-ingenol. 
   
   
       11 . Use of an active fraction of a polar solvent extract of an Euphorbiaceae plant latex of any of  claims 1  to  10 , characterized by the fact that it is to obtain a useful composition or medicine for the treatment of diseases related to cell proliferation. 
   
   
       12 . Use of one or more of 3-(2,4,6-dodecatrienoyl)-ingenol and 3-(2,4,6,8-tetradecatetranoyl)-ingenol, characterized by the fact ft to obtain a useful composition or medicine for the treatment of diseases concerning cell proliferation. 
   
   
       13 . A composition containing an effective amount of said active fraction of any of  claims 1  to  10 , or one or more of 3-(2,4,6-dodecatrienoyl)-ingenol and 3-(2,4,6,8-tetradecatetranoyl)-ingenol, and pharmaceutically acceptable excipients. 
   
   
       14 . The composition of  claim 13 , characterized by the fact that it contains about 0.001% to about 95% of said active fraction of one of  claims 1  to  11 . 
   
   
       15 . The composition of  claim 13 , characterized by the fact that it contains about 0.1 mg to 2000 mg, more particularly about 10 mg to about 100 mg, of one or more of 3-(2,4,6-dodecatrienoyl)-ingenol and 3-(2,4,6,8-tetradecatetranoyl)-ingenol. 
   
   
       16 . Use of the composition of  claim 13 , characterized by the fact that it is to obtain a useful composition or medicine for the treatment of diseases related to cell proliferation. 
   
   
       17 . Use of any of  claims 11  or  12 , characterized by the fact that said disease is cancer. 
   
   
       18 . The use of  claim 17 , characterized by the fact that the cancer is lung, breast, colon, kidney, ovary or prostate cancer. 
   
   
       19 . A method of treatment of diseases related to proliferative cells, characterized by the fact that a patient in need of said treatment receives an effective amount of an active fraction of any of  claims 1  to  10  and/or one or more compounds with molecular weight between about 500 and about 600 contained in an active fraction of any of  claims 1  to  10  and/or one or more of 3-(2,4,6-dodecatrienoyl)-ingenol and 3-(2,4,6,8-tetradecatetranoyl)-ingenol, or a composition comprising an effective amount of an active fraction of any of  claims 1  to  10  and/or one or more compounds with molecular weight between about 500 and about 600 contained in an active fraction of any of  claims 1  to  10 , and/or one or more of 3(2,4,6-dodecatrienoyl)-ingenol and 3-(2,4,6,8-tetradecatetranoyl)-ingenol. 
   
   
       20 . The method of  claim 19 , characterized by the fact that said disease is cancer. 
   
   
       21 . The method of  claim 20 , characterized by the fact that the cancer is lung, breast, colon, kidney, ovary or prostate cancer. 
   
   
       22 . A process to obtain an active fraction of a polar solvent extract of an Euphorbiaceae plant latex, characterized by the fact that it comprises:
 a) mixing latex from an Euphorbiaceae plant with a substantially non-polar solvent;   b) addition of a substantially polar solvent to the mixture of item a) or to the decanted solid phase after mixing item a), under enough agitation to allow effective contact between the solvent and itself;   c) separation of the polar phase;   d) fractioning of the polar phase in a chromatographic column;   e) isolation of the fraction corresponding to higher molecular weights.   
   
   
       23 . The process of  claim 22 , characterized by the fact that one or more of the following limitations are used:
 latex is fresh;   the plant is  Euphorbia,  particularly  Euphorbia tirucalli L.;      the substantially non-polar solvent is hexane;   the polar solvent has a dipole moment between about 1.60 and about 1.80 and dielectric constant between about 15 and about 18;   the stationary phase of the chromatographic column is Sephadex G75 and dragging is made with a mixture of hexane: ethyl acetate;   the polar phase is fractioned in eight fractions, so that the isolation of the active fraction with higher molecular weights is made with fractions 6, 7 and 8, preferably just fraction 7, more preferably molecules with molecular weight between 500 and 600.