Alpha-ketoglutarates of active ingredients and compositions containing same

Abstract

Novel stable and pharmacologically acceptable salts of L-carnitine and lower alkanoyl L-carnitines with alpha-ketoglutaric acid are disclosed as well as the compositions useful as dietary and dietetic supplements, nutraceuticals or drugs containing same.

1 . L-carnitine and lower alkanoyl L-carnitine alpha-ketoglutarate of formula  
       
         
           
           
               
               
           
         
       
       wherein: 
 A −  is the alpha-ketoglutarate anion; and  
 R is hydrogen or a straight- or branched-chain lower alkanoyl having 2-5 carbon atoms.  
 
     
     
         2 . The alpha-ketoglutarate of  claim 1 , wherein R is an alkanoyl selected from the group consisting of acetyl, propionyl, valeryl and isovaleryl.  
     
     
         3 . L-carnitine alpha-ketoglutarate.  
     
     
         4 . Acetyl L-carnitine alpha-ketoglutarate.  
     
     
         5 . Propionyl L-carnitine alpha-ketoglutarate.  
     
     
         6 . Valeryl L-carnitine alpha-ketoglutarate.  
     
     
         7 . Isovaleryl L-carnitine alpha-ketoglutarate.  
     
     
         8 . An orally parenterally or sublingually administrable composition comprising: 
 (a) an L-carnitine or a lower alkanoyl L-carnitine alpha-ketoglutarate of formula:                           wherein: 
 A −  is the alpha-ketoglutarate anion; and  
 R is hydrogen or a straight- or branched-chain lower alkanoyl having 2-5 carbon atoms; and  
   (b) a pharmacologically acceptable excipient.    
     
     
         9 . The composition of  claim 8 , wherein the alpha-ketoglutarate is selected from the group consisting of: 
 L-carnitine alpha-ketoglutarate;    acetyl L-carnitine alpha-ketoglutarate;    propionyl L-carnitine alpha-ketoglutarate;    valeryl L-carnitine alpha-ketoglutarate; and    isovaleryl L-carnitine alpha-ketoglutarate.    
     
     
         10 . The composition of claims  8  or  9  as a pharmaceutical composition, OTC composition, nutritional supplement, dietary supplement, health food, nutraceutical, veterinary product or fodder.  
     
     
         11 . The composition of any one of claims  8 - 10  which further comprises nutritional or pharmacological active ingredients, fillers, binders, lubricants, mold-release agents, flow-regulating agents, dispersing agents, colorants and flavoring agents.  
     
     
         12 . The composition of  claim 11  wherein the further nutritional or pharmacological active ingredients are selected from vitamins, amino acids, proteins mineral salts antioxidants and coenzymes.  
     
     
         13 . The composition of any one of claims  8 - 12  in the form of tablets, chewable tablets, pills, troches, lozenges, capsules, powders, granulates, phials, solutions, elixirs or drops.  
     
     
         14 . The composition of any one of claims  8 - 13 , in unit dosage form, comprising an amount of a ketoglutarate of claims  1 - 7  corresponding to about 50-1000 mg, preferably about 100-500 mg, of L-carnitine or alkanoyl L-carnitine as inner salts.  
     
     
         15 . The composition of  claim 14 , comprising:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   L-carnitine alpha-ketoglutarate 
                   mg 
                   500 
                 
                     
                   Cocarboxylase 
                   mg 
                   2 
                 
                     
                   Vit. B 6   
                   mg 
                   5 
                 
                     
                   Vit. E 
                   mg 
                   5 
                 
                     
                   Vit. PP 
                   mg 
                   20 
                 
                     
                   Vit. C 
                   mg 
                   50 
                 
                     
                   Coenzyme Q 10   
                   mg 
                   25 
                 
                     
                   Selenomethionine 
                   μg 
                   50 
                 
                     
                   Magnesium 
                   mg 
                   25 
                 
                     
                   Calcium 
                   mg 
                   25 
                 
                     
                   Zinc 
                   mg 
                   3 
                 
                     
                     
                 
                     
                     
                 
             
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         16 . The composition of  claim 14 , comprising:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   L-carnitine alpha-ketoglutarate 
                   mg 
                   200 
                 
                     
                   Acetyl L-carnitine alpha-ketoglutarate 
                   mg 
                   200 
                 
                     
                   Propionyl L-carnitine alpha-ketoglutarate 
                   mg 
                   200 
                 
                     
                   Cocarboxylase 
                   mg 
                   2 
                 
                     
                   Vit. B 6   
                   mg 
                   5 
                 
                     
                   Vit. E 
                   mg 
                   5 
                 
                     
                   Vit. PP 
                   mg 
                   20 
                 
                     
                   Vit. C 
                   mg 
                   50 
                 
                     
                   Coenzyme Q 10   
                   mg 
                   25 
                 
                     
                   Selenomethionine 
                   μg 
                   50 
                 
                     
                   Magnesium 
                   mg 
                   25 
                 
                     
                   Calcium 
                   mg 
                   25 
                 
                     
                   Zinc 
                   mg 
                   3 
                 
                     
                     
                 
                     
                     
                 
             
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         17 . Use of an alpha-ketoglutarate of claims  1 - 7  for preparing an orally, parenterally or sublingually administrable composition for the prevention or treatment of organic or tissue disorders brought about by anoxia or inadequate energy supply or metabolic dysfunctions such as those occurring during strenuous physical exercise, in post-infarction states, cardiopathies or neuropathies, in subjects suffering from phenylketonuria and chronic uremic patients undergoing regular haemodialytic treatment.