Valsartan salts

Abstract

The invention relates to new salts of valsartan or crystalline, also partly crystalline and amorphous salts of valsartan, the respective production and usage, and pharmaceutical preparations containing such a salt.

What we claim is:  
     
         1 . A salt of valsartan, selected from the group consisting of the monosodium salt, the monopotassium salt, the disodium salt, the dipotassium salt, the magnesium salt, the calcium salt, the bis-diethylammonium salt, the bis-dipropylammonium salt, the bis-dibutylammonium salt, the mono-L-arginine salt, the bis-L-arginine salt, the mono-L-lysine salt and the bis-L-lysine salt, as well as salt mixtures thereof.  
     
     
         2 . A salt according to  claim 1  in crystalline, partially crystalline or amorphous form.  
     
     
         3 . The calcium salt or the magnesium salt of valsartan according to  claim 1 .  
     
     
         4 . The tetrahydrate of the calcium salt of valsartan according to  claim 3 .  
     
     
         5 . The tetrahydrate according to  claim 4 , characterised by 
 (i) an X-ray powder pattern taken with a Guinier camera comprising the following interlattice plane intervals: 
 d in [Å]: 16.1±0.3, 9.9±0.2, 9.4±0.2, 7.03±0.1, 6.50±0.1, 5.87±0.05, 5.74±0.05, 4.95±0.05, 4.73±0.05, 4.33±0.05, 4.15±0.05, 4.12±0.05, 3.95±0.05; or  
   (ii) an ATR-IR spectrum having the following absorption bands expressed in reciprocal wave numbers (cm −1 ): 
 1621 (st); 1578 (m); 1458 (m); 1441 (m); 1417 (m); 1364 (m); 1012 (m); 758 (m); 738 (m); 696 (m); 666 (m).  
   
     
     
         6 . The hexahydrate of the magnesium salt of valsartan according to  claim 1 .  
     
     
         7 . The hexahydrate according to  claim 6 , characterised by 
 (i) an X-ray powder pattern taken with a Guinier camera comprising the following interlattice plane intervals: 
 d in [Å]: 19.7±0.3, 10.11±0.2, 9.8±0.2, 7.28±0.1, 5.81±0.05, 5.68±0.05, 5.03±0.05, 4.88±0.05, 4.18±0.05, 4.08±0.05, 3.46±0.05; or  
   (ii) an ATR-IR spectrum having the following absorption bands expressed in reciprocal wave numbers (cm −1 ): 
 3378 (m); 3274 (m); 2956 (m); 1619 (st); 1557 (m); 1464 (m); 1419 (m); 1394 (st); 1374 (m); 1175 (m); 836 (m); 820 (s); 766 (st); 751 (m); 741 (st); 732 (st).  
   
     
     
         8 . A salt according to one of claims  1 - 7  in the form of a solvate.  
     
     
         9 . A salt according to one of claims  1 - 8  in the form of a hydrate.  
     
     
         10 . A salt according to one of claims  1 - 9  in a form selected from the group consisting of 
 (i) a crystalline form;  
 (ii) a partly crystalline form;  
 (iii) an amorphous form; and  
 (iv) a polymorphous form.  
 
     
     
         11 . Pharmaceutical preparation containing a compound according to one of  claims 1  to  10  and a pharmaceutically acceptable excipient or additive.  
     
     
         12 . Pharmaceutical preparation according to  claim 11 , containing a salt according to one of claims  1 - 9  in combination with at least one composition selected from the group consisting of a: 
 (i) HMG-Co-A reductase inhibitor or a pharmaceutically acceptable salt thereof,  
 (ii) angiotensin converting enzyme (ACE) Inhibitor or a pharmaceutically acceptable salt thereof,  
 (iii) calcium channel blocker or a pharmaceutically acceptable salt thereof,  
 (iv) aldosterone synthase inhibitor or a pharmaceutically acceptable salt thereof,  
 (v) aldosterone antagonist or a pharmaceutically acceptable salt thereof,  
 (vi) dual angiotensin converting enzyme/neutral endopeptidase (ACE/NEP) inhibitor or a pharmaceutically acceptable salt thereof,  
 (vii) endothelin antagonist or a pharmaceutically acceptable salt thereof,  
 (viii) renin inhibitor or a pharmaceutically acceptable salt thereof, and  
 (ix) diuretic or a pharmaceutically acceptable salt thereof.  
 
     
     
         13 . Use of a compound according to one of  claims 1  to  10  in the preparation of a medicament for the prophylaxis or treatment of diseases and conditions which can be inhibited by blocking the AT 1  receptor.  
     
     
         14 . Process for the manufacture of a salt according to  claim 1 , characterised in that 
 (i) valsartan and the appropriate base are added to a water-containing organic solvent,    (ii) the solvent is concentrated, for example by heating, if necessary under reduced pressure or by slowly evaporating, e.g. at room temperature,    (iii) the residue of evaporation is equilibrated with the required amount of water by 
 (a) suspending the residue of evaporation, which is advantageously still warm, and which still contains some water, in an appropriate solvent or  
 (b) by equilibrating the water excess in the solvent; whereby in a) and b) the existing or added water is present in a quantity in which the water dissolves in the organic solvent and does not form an additional phase; and  
   (iv) the salt obtained is isolated.