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−bacteria, and/or anti-fungal composition comprising as active blend trans-cinnamaldehyde and a potentiating agent, and to the potentiating agent. In particular this composition is intended for preventing and/or treating microbial infection in an animal.

1 . Composition comprising:
 a synergistic active blend comprising, or consisting of:
 trans-cinnamaldehyde 
 a potentiating agent comprising or consisting of:
 at least one terpenoïd, chosen from mono and sesquiterpenoïds and/or 
 at least one derivate from trans-cinnamaldehyde, belonging to the group of phenylpropanoïds, with a molecular weight below 200 g/mol, 
 optionally phenylpropane derivative 
 
 optionally a drug, in particular an antibiotic or an antiviral drug, 
 optionally a carrier. 
   
     
     
         2 . Composition according to  claim 1 , wherein the composition is free of coumarin or safrole, or is free of coumarin and safrole. 
     
     
         3 . Composition according to  claim 1 , wherein the terpenoïd is chosen from menthanes, acyclic monoterpenoïds and caryophyllanes. 
     
     
         4 . Composition according to  claim 1 , wherein phenylpropane derivative is selected from the group consisting of apiole, coniferyl benzoate, chavicol, cinnamein, vanillin and benzyle benzoate. 
     
     
         5 . Composition according to  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, 
         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. 
       
     
     
         6 . Composition according to  claim 5 , wherein the trans-cinnamaldehyde derivate is chosen from trans-2-methoxycinnamaldehyde and cinnamyl acetate. 
     
     
         7 . Composition according to  claim 1 , wherein the potentiating agent comprises, or consists of:
 at least one terpenoïd 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.   
     
     
         8 . Composition according to  claim 1 , wherein it comprises at least one antibiotic. 
     
     
         9 - 12 . (canceled) 
     
     
         13 . Method to improve the antimicrobial activity of cinnamaldehyde wherein is added to said cinnamaldehyde a potentiating agent comprising or consisting of:
 at least one terpenoïd, chosen from mono and sesquiterpenoïds and/or   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,   optionally phenylpropane derivative.   
     
     
         14 . Method to clean a surface wherein is applied a composition according to  claim 1 . 
     
     
         15 . Method to conserve food or a cosmetic composition wherein is applied a composition according to  claim 1 . 
     
     
         16 . Composition according to  claim 1  wherein the drug is an antibiotic or an antiviral drug. 
     
     
         17 . Composition according to  claim 3  wherein the terpenoïd is chosen from cineol, linalool and beta-caryophyllene 
     
     
         18 . Composition according to  claim 6 , wherein the amount of trans-cinnamadehyde derivate ranges from 1 to 50% by weight compared to the total weight of the active blend. 
     
     
         19 . Composition according to  claim 8 , 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.   
     
     
         20 . Method for antimicrobial prevention or treatment wherein is administered to a patient in need thereof a composition according to  claim 1 . 
     
     
         21 . Method for preventing or treating infections resulting from resistant bacteria and/or fungi and/or viruses wherein is administered to a patient in need thereof a composition according to  claim 1 . 
     
     
         22 . Method according to  claim 20  wherein the composition is active toward drug-resistant Gram−bacteria strains. 
     
     
         23 . Method according to  claim 22  wherein the composition is active toward at least 1, 2, 3, 4, 5, 6 or 7 drug-resistant Gram−bacteria strains selected from:
   Pseudomonas;    
   Acinetobacter;    
   Escherichia;    
   Enterobacter;    
   Serratia;    
   Citrobacter ; and 
   Klebsiella.    
 
     
     
         24 . Method according to  claim 13  wherein the antimicrobial activity is an anti-bacterial or anti-fungal or anti-viral activity. 
     
     
         25 . Method according to  claim 21  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. 
     
     
         26 . Method according to  claim 25  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. 
     
     
         27 . Conservative agent comprising a composition according to  claim 1 .