Patent Publication Number: US-4321264-A

Title: α-methyldopa compositions

Description:
BACKROUND OF THE INVENTION 
     The present invention concerns a pharmaceutical composition for treating hypertension. The components are L-α-methyl-3,4-dihydroxyphenylanine and salicylamide, phenylglyoxal or L-ascorbic acid. 
     L-α-methyl-3,4-dihydroxyphenylalanine (α-methyldopa) is a commercial antihypertensive agent. [see Merck Index 9th Ed., Item 5925 (1976)]. Salicylamide is a commercial analgesic. [Merck Index 9th Ed., Item 8089 (1976)]. Phenylglyoxal apparently has no commercial pharmaceutical utility. L-ascorbic acid is a vitamin. 
     The combination of methyldopa with salicylamide, phenylglyoxal or L-ascorbic acid has been found to have enhanced antihypertensive properties. 
     SUMMARY OF THE INVENTION 
     A pharmaceutical composition for treating hypertension containing (A) α-methyldopa and (B) salicylamide, phenylglyoxal or L-ascorbic acid and a method of treatment. 
    
    
     DESCRIPTION OF THE PREFERRD EMBODIMENT 
     An embodiment of the present invention is a pharmaceutical composition for treating hypertension containing (A) L-α-methyl-3,4-dihydroxyphenylalanine (α-methyldopa) and (B) salicylamide, phenylglyoxal, or L-ascorbic acid wherein the weight ratio of (A):(B) is at least about 3:1. 
     The (A):(B) weight ratio in the composition of the present invention may be varied. A preferred weight ratio of (A):(B) is about 16:1 to about 3:1. A more preferred (A):(B) weight ratio is about 12:1 to about 3:1. A still more preferred weight ratio is about 8:1 to about 4:1. 
     One preferred embodiment of the present inventive composition is one containing α-methyldopa and phenylglyoxal. More preferred embodiments of this composition contain weight ratios as set out above. 
     Another preferred embodiment of the present inventive composition is one containing α-methyldopa and L-ascorbic acid. More preferred embodiments of this combination have weight ratios as set out above. 
     Still another preferred embodiment of the present inventive composition is one containing α-methyldopa and salicylamide. More preferred embodiments of this combination have weight ratios as recited above. 
     The compositions of the present invention may be administered either orally or parenterally in treating hypertension in humans. Appropriate dosage forms are used. Oral administration is preferred. Suitable oral dosage forms may be solid e.g. tablets, troches, capsules and the like, or liquid e.g. solution, suspension, emulsion and the like. Where necessary, or desirable, common pharmaceutically acceptable compounding ingredients i.e. diluents, carriers, processing acids, etc., may be used in preparing the dosage forms. Conventional procedures, compounding ingredients and equipment are used to prepare the oral and/or parenteral dosage forms. 
     The weight ratio of the (A) and (B) components in the dosage form will be within the ranges already set out above. 
     In treating hypertension in humans, an anti-hypertensive effective amount of the composition containing the (A) and (B) components is administered. The daily dosage of the composition will be varied depending on various factors e.g. the severity of the hypertension (high blood pressure), the weight of the patient etc. Generally, daily dosages may range up to about 3000 mg, preferably from about 250 mg to about 2000 mg, and more preferably from about 500 mg to about 1500 mg. 
     The enhanced effectiveness of the present composition as an antihypertensive agent was demonstrated in an in vivo test using spontaneously hypertensive (SH) rats. The representative combination tested contained α-methyldopa and salicylamide. The data for this in vivo test is tabulated below: 
     
                                           TABLE 1                                 
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ANTIHYPERTENSIVE ACTIVITY IN SH RAT                                       
ORAL ADMINISTRATION                                                       
                          Mean Arterial Pressure.sup.1 (mm/Hg)            
       Composition                                                        
               Dose   No. of                                              
                          Hours After Treatment                           
Test No.                                                                  
       Containing                                                         
               (mg/kg)                                                    
                      Rats                                                
                          0  1/2                                          
                                1  2  4  8  12 18                         
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1      α-Methyldopa                                                 
               80     10  164                                             
                             155                                          
                                164                                       
                                   148                                    
                                      141                                 
                                         152                              
                                            158                           
                                               160                        
2      α-Methyldopa                                                 
               80     16  173                                             
                             178                                          
                                172                                       
                                   163                                    
                                      152                                 
                                         154                              
                                            166                           
                                               169                        
3      α-Methyldopa                                                 
               80                                                         
       +       +      5   174                                             
                             162                                          
                                161                                       
                                   153                                    
                                      142                                 
                                         136                              
                                            150                           
                                               148                        
       Salicylamide                                                       
               10                                                         
4      α-Methyldopa                                                 
               80                                                         
       +       +      3   186                                             
                             172                                          
                                170                                       
                                   167                                    
                                      154                                 
                                         170                              
                                            168                           
                                               176                        
       Salicylamide                                                       
               20                                                         
5      α-Methyldopa                                                 
               80                                                         
       +       +      2   164                                             
                             144                                          
                                158                                       
                                   156                                    
                                      158                                 
                                         160                              
                                            158                           
                                               160                        
       Salicylamide                                                       
               40                                                         
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 .sup.1 Average   The data shows that the combination of α-methyldop
 and salicylamide, weight ratio 8:1 and 4:1, is more effective than
 α-methyldopa in reducing means arterial pressure of SH rats. This
 indicates that the compositions of the present invention would be more
 effective than α-methyldopa in treating hypertensive humans.
 
    
     Claims to the invention follow.