Dietary and pharmaceutical compositions containing tricyclic diterpenes and their derivatives and their uses

Abstract

The present invention refers to tricyclic diterpenes and their derivatives of the formulae (I) and (II), wherein R 1 is hydrogen or C 1-6 -alkyl; R 2 is hydroxy, C 3-5 -acyloxy, hydroxymethyl, 1,3-dihydroxypropyl or C 1-6 -alkyl; R 3 and R 4 independently from each other are hydrogen, hydroxy, hydroxymethyl, C 1-5 -acyloxy or C 1-6 -alkoxy; R 5 is C 1-6 -alkyl, hydroxymethyl carboxy or methoxycarbonyl; R 9 is hydrogen, hydroxymethyl, methoxy, oxo or C 1-5 -acyloxy; R 10 is hydrogen, or R 5 and R 9 taken together are —CH 2 —O— or —O—CH 2 —; or R 5 and R 10 taken together are —CO—O—, —O—CO—, —CH 2 —O— or —O—CH 2 —; R 6 is hydrogen, or R 5 and R 6 together form a bond; R 7 and R 8 independently from each other are C 1-6 -alkyl, carboxy, x-hydroxy-Cx-alkyl (with x being an integer from 1 to 6), or C 1-6 -alkoxycarbonyl with the proviso that at least one of R 7 and R 8 is C 1-6 -alkyl; R 11 and R 12 are both hydrogen or R 11 and R 12 together are oxo, with the further proviso for formula (I) that if R 2 is hydroxy R 1 is C 1-6 -alkyl, for use as medicaments for the treatment of a disorder connected to impaired neurotransmission, as well as to dietary and pharmaceutical compositions and their uses.

1 . A dietary or pharmaceutical composition containing at least a tricyclic diterpene or its derivative of the formulae I and II, 
     
       
         
         
             
             
         
       
     
     wherein R 1  is hydrogen or C 1-6 -alkyl; R 2  is hydroxy, C 3-5 -acyloxy, hydroxymethyl, 1,3-dihydroxypropyl or C 1-6 -alkyl; R 3  and R 4  independently from each other are hydrogen, hydroxy, hydroxymethyl, C 1-5 -acyloxy or C 1-6 -alkoxy; R 5  is C 1-6 -alkyl, hydroxymethyl, carboxy or methoxycarbonyl; R 9  is hydrogen, hydroxymethyl, methoxy, oxo or C 1-5 -acyloxy; R 10  is hydrogen, or R 5  and R 9  taken together are —CH 2 —O— or —O—CH 2 —; or R 5  and R 10  taken together are —CO—O—, —O—CO—, —CH 2 —O— or —O—CH 2 —; R 6  is hydrogen, or R 5  and R 6  together form a bond; R 7  and R 8  independently from each other are C 1-6 -alkyl, carboxy, x-hydroxy-C x -alkyl (with x being an integer from 1 to 6), or C 1-6 -alkoxycarbonyl with the proviso that at least one of R 7  and R 3  is C 1-6 -alkyl; R 11  and R 12  are both hydrogen or R 11  and R 12  together are oxo, 
     with the further proviso for formula I that if R 2  is hydroxy R 1  is C 1-6 -alkyl. 
   
   
       2 . The dietary or pharmaceutical composition according to  claim 1  containing at least a tricyclic diterpene or its derivative of the formulae I and II, wherein R 1  is hydrogen or iso-propyl; R 2  is hydroxy or iso-propyl; R 3  and R 4  independently from each other are hydrogen, hydroxy or methoxy; R 5  is methyl or carboxy; R 9  is hydrogen, oxo or methoxy; R 10  is hydrogen or R 5  and R 9  taken together are —CH 2 —O— or —O—CH 2 —; or R 5  and R 10  taken together are —CO—O—, —O—CO—, —CH 2 —O— or —O—CH 2 —; R 6  is hydrogen or R 5  and R 6  together form a bond; R 7  and R 8  independently from each other are methyl, carboxy, hydroxymethyl or methoxycarbonyl with the proviso that at least one of R 7  and R 8  is methyl, and with the further proviso for formula I that if R 2  is hydroxy R 1  is iso-propyl. 
   
   
       3 . The dietary or pharmaceutical composition according to  claim 1 , wherein the tricyclic diterpene and its derivative of the formulae I and II are selected from the group consisting of carnosic acid, carnosic acid 12-methyl ether, 7-oxocallitrisic acid, totarol, 16-hydroxytotarol, totarol-19-carboxylic acid methyl ester, 20-deoxo-carnosol, 7-methylrosmanol, sageone, 8,11,13-abietatriene-11,12,20-triol, royleanonic acid and ferruginol, preferably wherein the tricyclic diterpene is carnosic acid or 7-oxocallitrisic acid, more preferably wherein it is carnosic acid. 
   
   
       4 . The dietary composition according to  claim 1  being in form of food such as dairy products (yoghurts), in form of fortified food such as cereal bars and bakery items such as cakes and cookies, in form of dietary supplements such as tablets, pills, granules, dragees, capsules, and effervescent formulations, in form of non-alcoholic drinks such as soft drinks, sport drinks, fruit juices, lemonades, near-water drinks, teas and milk based drinks, in form of liquid food such as soups and dairy products (muesli drinks). 
   
   
       5 . Use of the dietary composition according to  claim 1  as antidepressant, mood/vitality improver, stress reliever, condition improver, reducer of anxiety, reducer of obsessive-compulsive behaviour, relaxant, sleep improver and/or insomnia alleviator. 
   
   
       6 . Tricyclic diterpene or its derivative of the formulae I and II as defined in  claim 1  for use as medicament. 
   
   
       7 . The tricyclic diterpene or its derivative of the formulae I and II as defined in  claim 1  for use as medicament for the treatment of a disorder connected to impaired neurotransmission. 
   
   
       8 . The tricyclic diterpene or its derivative of the formulae I and II according to  claim 1  for use as an antidepressant, mood/vitality improver, stress reliever, condition improver, reducer of anxiety, reducer of obsessive-compulsive behaviour, relaxant, sleep improver and/or insomnia alleviator. 
   
   
       9 . Use of a tricyclic diterpene or a derivative thereof of the formulae I and II as defined in  claim 1  for the manufacture of a composition for the treatment of a disorder connected to impaired or reduced neurotransmission. 
   
   
       10 . The use according to  claim 9 , wherein the composition is an antidepressant, a mood/vitality improver, a stress reliever, a condition improver, a reducer of anxiety, a reducer of obsessive-compulsive behaviour, a relaxant, a sleep improver and/or an insomnia alleviator. 
   
   
       11 . A method for the treatment of a disorder connected to impaired neurotransmission in animals including humans, said method comprising administering an effective dose of a tricyclic diterpene and/or a derivative thereof according to the formulae I and II as defined in  claim 1  to animals including humans which are in need thereof. 
   
   
       12 . The method according to  claim 11 , wherein the animal is a human, a pet animal or a farm animal.