Medicinal association of a biguanine and a carrier, for example metformin and arginine

Abstract

A medicinal combination for the treatment of diabetes, in particular of type 2 diabetes, combining a biguanide, in particular an N-dimethylbiguanide, as a first medicament, and an agent for transporting the said biguanide, as a second medicament, said combination comprising: e [sic] a therapeutically active quantity of the biguanide f [sic] and a quantity of transporting agent, previously determined to potentiate the therapeutic activity of the biguanide according to (a).

1 . A medicinal combination for the treatment of diabetes, combining a biguanide, as a first medicament, and an agent for transporting said biguanide, as a second medicament, said combination comprising: 
 (a) a therapeutically active quantity of the biguanide; and    (b) a quantity of the transporting agent, previously determined to potentiate the therapeutic activity of the biguanide.    
   
   
       2 . The medicinal combination as claimed in  claim 1 , wherein the biguanide and the transporting agent are in an equimolar quantity.  
   
   
       3 . The medicinal combination as claimed in  claim 1 , wherein the biguanide is metformin.  
   
   
       4 . The medicinal combination as claimed in  claim 1 , wherein the transporting agent is a biogenic amine.  
   
   
       5 . The medicinal combination as claimed in  claim 1 , wherein the biguanide and/or the transporting agent are in a form suitable for their controlled release respectively.  
   
   
       6 . The medicinal combination as claimed in  claim 5 , chemically put together for the controlled release of at least biguanide, wherein said medicinal combination is an active compound of general formula  
     
       
         
         
             
             
         
       
     
     capable of restoring at least the entity A by cleavage, in vivo, of the corresponding attachment between A′ and V′, wherein: 
 V is a biogenic vectorization compound, of general formula X-R-Y, where: 
 R represents an aliphatic, cyclic or alicyclic, saturated or unsaturated hydrocarbon chain of 2 to 10 carbon atoms, which is optionally substituted with C1 to C5 alkyl groups and/or hydroxyl groups, and  
 X and Y are each a free acid, amine or alcohol function; and  
 
 A and C are two respectively different active principles, namely the biguanide and the transporting agent, one of which comprises a chemical function complementary to the function X, capable of reacting with the function X so as to give an ionic A′-V′ or covalent A′-V′ attachment which can be cleaved in vivo, and the other of which comprises a chemical function complementary to the function Y, capable of reacting with the function Y so as to give an ionic V′-C′ or covalent V′-C′ attachment which can be cleaved in vivo.  
 
   
   
       7 . The medicinal combination as claimed in  claim 6 , wherein the V′-C′ or V′-C′ attachment can be cleaved in vivo, and said active compound is also capable of restoring the entities V and C by said cleavage in vivo.  
   
   
       8 . The medicinal combination as claimed in  claim 7 , A being metformin, wherein the metformin is attached to the biogenic vectorization compound by salification of the terminal primary amine function of the metformin.  
   
   
       9 . The medicinal combination as claimed in  claim 7 , wherein, when C is arginine, the arginine is attached to the biogenic vectorization compound V using an acylation reaction.  
   
   
       10 . The medicinal combination as claimed in  claim 6 , wherein V is selected from the group consisting of oxalic, malonic, succinic, glutaric, adipic, pimelic, suberic, azelaic, sebactic, malic, isatic and phthalic acids.  
   
   
       11 . A method for treating diabetes, comprising administering an active compound of general formula  
     
       
         
         
             
             
         
       
     
     as claimed in  claim 6 .  
   
   
       12 . A process for preparing an active compound as claimed in  claim 6 , comprising the following steps: 
 (a) reaction by condensation and/or salification of the biogenic vectorization compound V with one of the active principles A or C,    (b) reaction by condensation and/or salification of the product of the reaction according to (a) with the other active principle C or A,    wherein: 
 the active compound is represented by formula III:  
                     
   
   
   
       13 . A pharmaceutical composition comprising at least one active compound as claimed in  claim 6 , in combination with one or more compatible and pharmaceutically acceptable vehicles, diluents, excipients or adjuvants.  
   
   
       14 . The pharmaceutical composition as claimed in  claim 13 , which makes it possible to adjust a daily dose in humans of between approximately 0.2 g and approximately 1 g of said active compound, to one or more doses.  
   
   
       15 . A medicinal combination as claimed in  claim 1 , wherein said combination is for treatment of type 2 diabetes.  
   
   
       16 . A medicinal combination as claimed in  claim 1 , wherein said biguanide is an N-dimethylbiguanide.  
   
   
       17 . A medicinal combination as claimed in  claim 4 , wherein said biogenic amine is selected from the group consisting of arginine, putrescine, cadaverine, spermidine and spermine.  
   
   
       18 . A medicinal combination as claimed in  claim 17 , wherein said biogenic amine is L-arginine.  
   
   
       19 . A medicinal combination as claimed in  claim 10 , wherein V is succinic acid.