Pharmaceutical composition comprising trans - cinnamaldehyde and its use in the treatment of infections

Abstract

This invention pertains to an anti-microbial, in particular anti-bacterial, more particularly against Gram negative bacteria, and/or anti-fungal composition comprising as active blend trans-cinnamaldehyde and a potentiating agent. In particular this composition is intended for preventing and/or treating microbial infection in an animal.

1 . A method for preventing or treating microbial infection, comprising administering to a subject an active blend comprising trans-cinnamaldehyde and a potentiating agent,
 wherein the antimicrobial effect of trans-cinnamaldehyde is potentiated by said potentiating agent,   wherein the active blend is free of coumarin or safrole or is free of coumarin and safrole,   wherein the potentiating agent comprises:
 at least one terpenoid, chosen from mono and sesquiterpenoids, and 
 at least one derivate from trans-cinnamaldehyde, either being a substituted trans-cinnamaldehyde or a compound corresponding to trans-cinnamaldehyde wherein the aldehyde function is replaced by another function, and 
 optionally phenylpropane derivative, 
   and wherein the potentiating agent comprises six compounds or less.   
     
     
         2 . The method according to  claim 1  wherein the antimicrobial effect of trans-cinnamaldehyde is an anti-bacterial or anti-fungal or anti-viral effect. 
     
     
         3 . The method of  claim 1 , in which the potentiating agent consists of 6 compounds or less. 
     
     
         4 . The method of  claim 1 , wherein the terpenoid is chosen from menthanes, acyclic monoterpenoids and caryophyllanes. 
     
     
         5 . The method of  claim 4 , wherein the terpenoid is chosen from cineol, linalool and beta-caryophyllene. 
     
     
         6 . The method of  claim 1 , wherein the phenylpropane derivative is selected from the group consisting of apiole, coniferyl benzoate, chavicol, cinnamein, vanillin and benzyle benzoate. 
     
     
         7 . The method of  claim 1 , wherein it comprises at least one trans-cinnamaldehyde derivate corresponding to Formula I: 
       
         
           
           
               
               
           
         
         wherein
 X represents —CH 2 OH, —CH 2 OY, —CHO, —COOH, —COOZ, —CO-Hal, 
 Y represents R a  or —COR a  with Ra being an alkyl comprising 1 to 6 carbon atoms, 
 Z represents an alkyl comprising 1 to 6 carbon atoms, 
 R 1  and R 2  represent independently, H, —OH, an alkyl comprising 1 to 6 carbon atoms, or an halogen atom 
 R 3  and R 4  represent independently, H, an alkyl comprising 1 to 6 atoms, an alkoxy comprising 1 to 6 carbon atoms or an halogen atom, 
 Hal represents an halogen atom, 
 
         and wherein when X is —CHO then at least one of R 1 , R 2 , R 3  and R 4  does not represent H. 
       
     
     
         8 . The method of  claim 7 , wherein the trans-cinnamaldehyde derivate is chosen from trans-2-methoxycinnamaldehyde and cinnamyle acetate. 
     
     
         9 . The method of  claim 8 , wherein the amount of trans-cinnamaldehyde derivate ranges from 1 to 50% by weight compared to the total weight of the active blend. 
     
     
         10 . The method of  claim 1 , wherein the potentiating agent comprises:
 at least one terpenoid and phenylpropane derivative in an amount ranging from 1 to 50% by weight compared to the total weight of the active blend,   at least one derivate from trans-cinnamaldehyde in an amount ranging from 1 to 50% by weight compared to the total weight of the active blend.   
     
     
         11 . The method of  claim 1 , for preventing or treating infections resulting from drug-resistant Gram negative bacteria strains. 
     
     
         12 . The method of  claim 11 , for preventing or treating infections resulting from 1, 2, 3, 4, 5, 6 or 7 drug-resistant Gram negative bacteria strains selected from:
   Pseudomonas;        Acinetobacter;        Escherichia;        Enterobacter;        Serratia;        Citrobacter ; and     Klebsiella.      
     
     
         13 . The method of  claim 1 , wherein the infection is selected from the group consisting of urinary system infection, respiratory system infection, digestive system infection, central nervous system infection, skin and soft tissues infection, bone infection, articulations infection, muscles infection, vasculary system infection and systemic infections. 
     
     
         14 . The method of  claim 13  for preventing or treating diseases or syndromes selected from the group consisting of bacteremia, Crohn disease, peptic ulcer, diabetic foot and eschars, septic shock, AIDS, Herpes, Hepatitis B and C and Influenza. 
     
     
         15 . The method of  claim 1 , wherein the subject is an animal. 
     
     
         16 . The method of  claim 15 , wherein the animal is chosen among cattle, swine, poultry, and pets. 
     
     
         17 . The method of  claim 1 , wherein an antibiotic is further administrated. 
     
     
         18 . The method of  claim 17 , wherein the antibiotic is selected among:
 antibiotics acting on the bacterial wall;   antibiotics operating the membranes of the cells, external membrane or cytoplasmic membrane;   antibiotics acting on the synthesis of proteins;   antibiotics blocking the synthesis of messenger RNA;   antibiotics acting on DNA;   antibiotics acting by competitive inhibition;   one of their pharmaceutically acceptable salts, and   one of their combinations.