Mixtures of cannabinoid compounds, and production and use thereof

Abstract

Described are also corresponding pharmaceutical formulations, cosmetic preparations and preparations for pleasure and/or nutrition, suitable for consumption, as well as methods for producing CBDV and THCV.

1 . A mixture comprising one or more compounds of formula (A) and/or one or more of their salts 
       
         
           
           
               
               
           
         
         wherein R1 is an aliphatic rest with none or one, two, three or more than three hydroxyl groups, wherein the total number of C-atoms in the aliphatic rest R1 is not bigger than 15, 
         an wherein the aliphatic rest is
 saturated or unsaturated, 
 branched or linear, and 
 acyclic or cyclic, 
 
         provided that if R1 is an aliphatic rest with no hydroxyl group, the compound(s) of the formula (A) or, respectively, the salt(s) thereof, is/are selected from the group consisting of the compounds cyclohexylcannabidivarinolat and hexylcannabidivarinolat as well as their salts, 
         wherein in the mixture the molar ratio of the total amount of compounds of the formula (A) and their salts to the amount of compounds of formula (V) (cannabidivarin, CBDV) 
       
       
         
           
           
               
               
           
         
       
       is bigger than 1:1 and simultaneously the molar ratio of the total amount of compounds of the formula (A) and their salts to the amount of compounds of formula (III) ((−)-trans-methylcannabidivarinolat) 
       
         
           
           
               
               
           
         
       
       is bigger than 1:1. 
     
     
         2 . The mixture according to  claim 1 , wherein the aliphatic rest of the compound of formula (A) is saturated and/or linear. 
     
     
         3 . The mixture according to  claim 1 , wherein the compound of the formula (A) is a compound of formula (A-I) 
       
         
           
           
               
               
           
         
         wherein applies: 
         each R 1 , independently of the meaning of each of the others of the overall n rests R 1  is H, alkyl with one or two C-atoms or OH, 
         R 2  is H or OH, 
         n is an integral number in the range from 2 to 10, 
         wherein at least one of the rests R 1  or the rest R 2  is OH, 
       
       and/or a compound of the formula ) (A-II) 
       
         
           
           
               
               
           
         
         wherein applies: 
         each R 1  independently of the meaning of each of the others of the overall n−1 rests R 1  is H, alkyl with one or two C-atoms or OH, 
         R 2  is H or OH, 
         n is an integral number in the range from 2 to 10, 
         wherein at least one of the rests R 1  or the rest R 2  is OH. 
       
     
     
         4 . A mixture according to  claim 1 , wherein the compound of the formula (A) is 
       (i) a compound of formula (A-III) 
       
         
           
           
               
               
           
         
         wherein applies: 
         each R 1  independently of the meaning of each of the others of the overall n−2 rests R 1  is H, alkyl with one or two C-atoms or OH, 
         R 2  is H or OH, 
         n is an integral number in the range from 2 to 10, 
         wherein at least one of the rests R 1  or the rest R 2  is OH, and/or 
       
       (ii) a compound of formula (A-IV) 
       
         
           
           
               
               
           
         
         wherein applies: 
         each R 1  independently of the meaning of each of the others of the overall n−1 rests R 1  is H, alkyl with one or two C-atoms or OH, and 
         n is an integral number in the range from 2 to 10. 
       
     
     
         5 . A mixture according to  claim 3 , wherein in the said formulas (A-I), (A-II), (A-III) or, respectively, (A-IV) each R 1  independently of the meaning of each of the others of the rests R 1  is H or OH. 
     
     
         6 . A mixture according to  claim 1 , wherein the compound of the formula (A) is a compound of formula (TV): 
       
         
           
           
               
               
           
         
       
     
     
         7 . A method of therapeutic treatment of a human or animal comprising administering to the human or animal a mixture of  claim 1 , or a compound of the formula (A), or salt thereof. 
     
     
         8 . A method for achieving an effect selected from the group consisting of:
 appetizing effect,   antiemetic effect for the inhibition of nausea and vomiting,   reduction of muscular cramps and spasticities,   alleviation of pain symptoms,   alleviation of migraine symptoms,   reduction of the intraocular pressure in the case of a glaucoma,   improved sentiment,   immune stimulation,   antiepileptic effect, and   as CB1 and/or CB2 receptor modulator;   the method comprising administering to the human or animal a mixture of  claim 1  or a compound of the formula (A), or salt thereof.   
     
     
         9 . A method for producing a mixture according to  claim 1  or a compound selected from the group consisting of cyclohexylcannabidivarinolat, hexylcannabidivarinolat and 2-hydroxyethylcannabidivarinolat or a salt thereof, comprising the following step:
 reacting an ester of the formula (IX) 
 
       
         
           
           
               
               
           
         
         wherein Y is an organic rest, 
         with an alcohol of the formula HO—X, 
         wherein X is an aliphatic rest with none, or one, two, three or more than three hydroxyl groups, 
         wherein the total amount of C-atoms in the aliphatic rest X is not bigger than 15, and 
         wherein the aliphatic rest is 
         saturated or unsaturated, 
         branched or linear, and 
         acyclic or cyclic, 
         provided that if X is an aliphatic rest with no hydroxyl group, the alcohol of the formula HO—X is selected from the group consisting of cyclohexanol and hexanol, 
         wherein Y is different from X and selected in a way that an alcohol of the formula HO—Y formed during the reaction boils at 1013 hPa at a lower temperature than the used alcohol of the formula HO—X. 
       
     
     
         10 . The method according to  claim 9  comprising the following step to produce the ester of formula (III):
 reacting menthadienol of the formula (I) with a divarin ester of the formula (II) to the corresponding ester of formula (III), 
 
       
         
           
           
               
               
           
         
       
     
     
         11 . A method for producing a mixture according to  claim 1  or a compound selected from the group consisting of cyclohexylcannabidivarinolat, hexylcannabidivarinolat and 2-hydroxyethylcannabidivarinolat or a salt thereof, comprising the following steps:
 (a) transesterification of a divarinacid ester,
 and 
 
 (b) reacting the divarinacid ester obtained by transesterification in step (a) with menthadienol to the corresponding compound of the formula (A). 
 
     
     
         12 . A method for producing THCV, comprising the production of a mixture according to  claim 1  or of a compound selected from the group consisting of cyclohexylcannabidivarinolat, hexylcannabidivarinolat and 2-hydroxyethylcannabidivarinolat or a salt thereof. 
     
     
         13 . A method according to  claim 12 , wherein the produced mixture or, respectively, the compound of the formula (A) or the salt thereof is treated in a way, that the compound of the formula (A) present in the mixture or, respectively, the salt thereof is decarboxylatingly saponified and the compound of the formula (V) (cannabidivarin, CBDV) 
       
         
           
           
               
               
           
         
       
       is formed. 
     
     
         14 . A compound selected from the group consisting of cyclohexylcannabidivarinolat, hexylcannabidivarinolat, and 2-hydroxyethylcannabidivarinolat. 
     
     
         15 . A pharmaceutical formulation or cosmetic preparation, comprising a mixture according to  claim 1 . 
     
     
         16 . A preparation for nutrition and/or pleasure, suitable for consumption, comprising a mixture according to  claim 1 . 
     
     
         17 . A pharmaceutical formulation or cosmetic preparation, comprising one or more compounds according to  claim 14  and/or one or more salts thereof. 
     
     
         18 . A preparation for nutrition and/or pleasure, suitable for consumption, comprising one or more compounds according to  claim 14  and/or one or more salts thereof. 
     
     
         19 . Crystalline cannabidivarin of formula (V)