Aromatic compositions for the inhibition of exoprotein production from gram positive bacteria

Abstract

Compositions including an aromatic compound for inhibiting the production of exoproteins by Gram positive bacteria are disclosed. The aromatic inhibitory compounds of the present invention have the general formula: wherein R 1 is selected from the group consisting of H, and salts thereof; R 5 is a monovalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 6 is a divalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 7 is a trivalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 8 is a monovalent substituted or unsubstituted saturated or unsaturated aliphatic hydrocarbyl moiety which may or may not be interrupted with hetero atoms; R 2 , R 3 , and R 4 are independently selected from the group consisting of H, OH, COOH, and —C(O)R 9 ; R 9 is hydrogen or a monovalent saturated or unsaturated aliphatic hydrocarbyl moiety.

1 . A composition for inhibiting production of exoprotein from Gram positive bacteria comprising an effective amount of a first active ingredient and an effective amount of a second active ingredient, the first active ingredient having the general formula:  
     
       
         
         
             
             
         
       
     
     wherein R 1  is selected from the group consisting of H,  
     
       
         
         
             
             
         
       
     
     and salts thereof; R 5  is a monovalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 6  is a divalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 7  is a trivalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 8  is a monovalent substituted or unsubstituted saturated or unsaturated aliphatic hydrocarbyl moiety which may or may not be interrupted with hetero atoms; R 2 , R 3 , and R 4  are independently selected from the group consisting of H, OH, COOH, and —C(O)R 9 ; R 9  is hydrogen or a monovalent saturated or unsaturated aliphatic hydrocarbyl moiety, and a pharmaceutically acceptable carrier, wherein the second active ingredient is myreth-3-myristate, and wherein the first active ingredient and the second active ingredient are effective in inhibiting the production of exoprotein from Gram positive bacteria.  
   
   
       2 . The composition as set forth in  claim 1  wherein R 1  is selected from the group consisting of  
     
       
         
         
             
             
         
       
     
     and salts thereof and wherein R 5  is a monovalent saturated aliphatic hydrocarbyl moiety having from 1 to about 15 carbon atoms.  
   
   
       3 . The composition as set forth in  claim 2  wherein R 5  is a monovalent saturated aliphatic hydrocarbyl moiety having from 1 to about 10 carbon atoms.  
   
   
       4 . The composition as set forth in  claim 1  wherein R 1  is selected from the group consisting of —R 6 C(O)H, —R 6 OH, —R 6 COOH, —OR 6 OH, and —OR 6 COOH and wherein R 6  is a divalent saturated or unsaturated aliphatic hydrocarbyl moiety having from 1 to about 15 carbon atoms.  
   
   
       5 . The composition as set forth in  claim 4  wherein R 6  is a divalent saturated or unsaturated aliphatic hydrocarbyl moiety having from 1 to about 10 carbon atoms.  
   
   
       6 . The composition as set forth in  claim 4  wherein R 6  is a divalent saturated or unsaturated aliphatic hydrocarbyl moiety having from 1 to about 6 carbon atoms.  
   
   
       7 . The composition as set forth in  claim 1  wherein R 1  is selected from the group consisting of  
     
       
         
         
             
             
         
       
     
     and wherein R 7  is a trivalent saturated or unsaturated aliphatic hydrocarbyl moiety having from 1 to about 15 carbon atoms.  
   
   
       8 . The composition as set forth in  claim 7  wherein R 7  is a trivalent saturated or unsaturated aliphatic hydrocarbyl moiety having from 1 to about 10 carbon atoms.  
   
   
       9 . The composition as set forth in  claim 7  wherein R 7  is a trivalent saturated or unsaturated aliphatic hydrocarbyl moiety having from 1 to about 4 carbon atoms.  
   
   
       10 . The composition as set forth in  claim 1  wherein R 1  is —R 6 OH, R 6  is a divalent saturated aliphatic hydrocarbyl moiety having from 1 to about 6 carbon atoms, and R 2 , R 3 , and R 4  are hydrogen.  
   
   
       11 . The composition as set forth in  claim 1  wherein R 1  is —R 6 COOH, R 6  is a divalent unsaturated aliphatic hydrocarbyl moiety having from 1 to about 6 carbon atoms, and R 2 , R 3 , and R 4  are hydrogen.  
   
   
       12 . The composition as set forth in  claim 1  wherein R 1  is —C(O)NH 2 , R 2  is OH, and R 3  and R 4  are hydrogen.  
   
   
       13 . The composition as set forth in  claim 1  wherein R 1  is  
     
       
         
         
             
             
         
       
     
     and R 5  is a monovalent saturated aliphatic hydrocarbyl group having from 1 to about 4 carbon atoms.  
   
   
       14 . The composition as set forth in  claim 1  wherein R 1  is  
     
       
         
         
             
             
         
       
     
     and R 7  is a trivalent saturated aliphatic hydrocarbyl moiety having from 1 to about 4 carbon atoms and R 8  is C(O)CH 3 .  
   
   
       15 . The composition as set forth in  claim 1  wherein R 2  is OH and R 3  is COOH.  
   
   
       16 . The composition as set forth in  claim 1  wherein the first active ingredient is selected from the group consisting of 2-phenylethanol, benzyl alcohol, trans-cinnamic acid, 4-hydroxybenzoic acid, methyl ester, 2-hydroxybenzoic acid, 2-hydroxybenzamide, acetyl tyrosine, 3,4,5-trihydroxybenzoic acid, lauryl 3,4,5-trihydroxybenzoate, phenoxyethanol, 4-hydroxy-3-methoxybenzoic acid, para-aminobenzoic acid, and acetaminophen.  
   
   
       17 . The composition as set forth in  claim 1  comprising from about 0.2 millimoles/liter to about 50 millimoles/liter of the first active ingredient.  
   
   
       18 . The composition as set forth in  claim 1  further comprising a pharmaceutically active material selected from the group consisting of antimicrobials, antioxidants, anti-parasitic agents, antipruritics, astringents, local anaesthetics and anti-inflammatory agents.  
   
   
       19 . A douche formulation for inhibiting the production of exoprotein from Gram positive bacteria comprising a vaginal cleansing formulation comprising a pharmaceutically acceptable carrier, an effective amount of a first active ingredient, and an effective amount of a second active ingredient the first active ingredient having the general formula:  
     
       
         
         
             
             
         
       
     
     wherein R 1  is selected from the group consisting of H,  
     
       
         
         
             
             
         
       
     
     and salts thereof; R 5  is a monovalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 6  is a divalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 7  is a trivalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 8  is a monovalent substituted or unsubstituted saturated or unsaturated aliphatic hydrocarbyl moiety which may or may not be interrupted with hetero atoms; R 2 , R 3 , and R 4  are independently selected from the group consisting of H, OH, COOH, and —C(O)R 9 ; R 9  is hydrogen or a monovalent saturated or unsaturated aliphatic hydrocarbyl moiety, wherein the second active ingredient is myreth-3-myristate, and wherein the first active ingredient and the second active ingredient are effective in inhibiting the production of exoprotein from Gram positive bacteria.  
   
   
       20 . A method of inhibiting the production of exoprotein from Gram positive bacteria comprising exposing said Gram positive bacteria to an effective amount of a first active ingredient and a second active ingredient, said first active ingredient having the general formula:  
     
       
         
         
             
             
         
       
     
     wherein R1 is selected from the group consisting of H,  
     
       
         
         
             
             
         
       
     
     and salts thereof; R 5  is a monovalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 6  is a divalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 7  is a trivalent saturated or unsaturated aliphatic hydrocarbyl moiety; R 8  is a monovalent substituted or unsubstituted saturated or unsaturated aliphatic hydrocarbyl moiety which may or may not be interrupted with hetero atoms; R 2 , R 3 , and R 4  are independently selected from the group consisting of H, OH, COOH, and —C(O)R 9 ; R 9  is hydrogen or a monovalent saturated or unsaturated aliphatic hydrocarbyl moiety, and said second active ingredient is myreth-3-myristate.