Novel Polymorph V of Torasemide

Abstract

The invention relates to a novel polymorph V of torasemide, to a process for its preparation, to its use as a raw material for the preparation of crystalline modifications I and III of torasemide, to amorphous torasemide modifications and to pharmaceutically acceptable salts of torasemide, to pharmaceutical forms containing the said novel polymorph V of torasemide as the active ingredient as well as to its use.

1 - 8 . (canceled)  
   
   
       9 . A process for the preparation of the crystalline modifications I, II and III torasemide or of an amorphous torasemide modification which comprises using as a raw material a polymorph V of torasemide characterized by the following data: 
 DSC: exothermic maximum at about 157.59° C. (onset at about 150.74° C.) with the heating rate of 10° C./min;    X-ray powder pattern (2Θ) : 5.610; 6.130; 7.480; 7.970; 9.310; 9.615; 10.835; 11.020; 12.340; 13.075; 13.460; 13.920; 14.200; 15.090; 16.080; 16.710; 17.445; 17.720; 18.460; 18.850; 19.825; 20.340; 20.990; 21.980; 22.075; 22.630; 22.935; 23.410; 23.845; 24.880; 25.560; 26.035; 27.285; 27.540; 28.170; 28.645; 29.350; 29.975; 30.575; 31.265; 32.300; 34.050; 35.650; 36.375; 37.100 and 38.145;    IR-characteristic absorption bands at 2671 to 3327 and at 1468 to 1705cm −1 .    
   
   
       10 . A process for the preparation of pharmaceutically acceptable salts of torasemide which comprises using a polymorph V of torasemide characterized by the following data: 
 DSC: exothermic maximum at about 157.59° C. (onset at about 150.74° C.) with the heating rate of 10° C./min;    X-ray powder pattern (2Θ): 5.610; 6.130; 7.480; 7.970; 9.310; 9.615; 10.835; 11.020; 12.340; 13.075; 13.460; 13.920; 14.200; 15.090; 16.080; 16.710; 17.445; 17.720; 18.460; 18.850; 19.825; 20.340; 20.990; 21.980; 22.075; 22.630; 22.935; 23.410; 23.845; 24.880; 25.560; 26.035; 27.285; 27.540; 28.170; 28.645; 29.350; 29.975; 30.575; 31.265; 32.300; 34.050; 35.650; 36.375; 37.100 and 38.145;    IR-characteristic absorption bands at 2671 to 3327 and at 1468 to 1705 cm −1 .    
   
   
       11 . (canceled)  
   
   
       12 . Pharmaceutical form, characterized in that as an active ingredient it contains an effective amount of a polymorph V of torasemide characterized by the following data: 
 DSC: exothermic maximum at about 157.59° C. (onset at about 150.74° C.) with the heating rate of 10° C./min;    X-ray powder pattern (2Θ): 5.610; 6.130; 7.480; 7.970; 9.310; 9.615; 10.835; 11.020; 12.340; 13.075; 13.460; 13.920; 14.200; 15.090; 16.080; 16.710; 17.445; 17.720; 18.460; 18.850; 19.825; 20.340; 20.990; 21.980; 22.075; 22.630; 22.935; 23.410; 23.845; 24.880; 25.560; 26.035; 27.285; 27.540; 28.170; 28.645; 29.350; 29.975; 30.575; 31.265; 32.300; 34.050; 35.650; 36.375; 37.100 and 38.145;    IR-characteristic absorption bands at 2671 to 3327 and at 1468 to 1705 cm −1 , without or in combination with one or more pharmaceutically acceptable additives.    
   
   
       13 . Pharmaceutical form according to  claim 12 , characterized in that it is a tablet, a capsule or an injection.  
   
   
       14 . A method of treatment selected from the group consisting of treating a patient in need of a diuretic; a patient suffering from 
 heart or heart tissue damages caused by metabolic or ionic abnormalities associated with ischemia; and    patient suffering from a treating a cenaitium selected from the group consisting of thrombosis, angina pectoris, asthma, hypertension, nephroedema, pulmonary edema, primary and secondary aldosteronism, Bartter's syndrome, tumors, glaucoma, decreasing of intraocular pressure, acute or chronic bronchitis, cerebral edema caused by trauma, ischemia, concussion of the brain, metastases or epileptic attacks, and nasal infections caused by allergens;    by administering to said patient an effecture amount of a polymorph V of torasemide characterized by the following data:    DSC: exothermic maximum at about 157.59° C. (onset at about 150.74° C.) with the heating rate of 10° C./min; 
 X-ray powder pattern (2Θ) : 5.610; 6.130; 7.480; 7.970; 9.310; 9.615; 10.835; 11.020; 12.340; 13.075; 13.460; 13.920; 14.200; 15.090; 16.080; 16.710; 17.445; 17.720; 18.460; 18.850; 19.825; 20.340; 20.990; 21.980; 22.075; 22.630; 22.935; 23.410; 23.845; 24.880; 25.560; 26.035; 27.285; 27.540; 28.170; 28.645; 29.350; 29.975; 30.575; 31.265; 32.300; 34.050; 35.650; 36.375; 37.100, and 38.145;  
   IR-characteristic absorption bands at 2671 to 3327 and at 1468 to 1705 cm −1 .    
   
   
       15 . Pharmaceutical form according to  claim 12  wherein said pharmaceutically acceptable additives are selected from the group consisting of sugar, starch, starch derivatives, cellulose, cellulose derivatives, mould release agents, antiadhesive agents and agents for regulating flowability.  
   
   
       16 . Pharmaceutical form according to  claim 12  wherein said polymorph V of torasemide is chemically pure.  
   
   
       17 . Pharmaceutical form according to  claim 12  wherein said polymorph V of torasemide contains no water.  
   
   
       18 . Pharmaceutical form according to  claim 12  wherein said polymorph V of torasemide contains no solvent.  
   
   
       19 . Pharmaceutical form according to  claim 15  wherein said polymorph V of torasemide is chemically pure.  
   
   
       20 . Pharmaceutical form according to  claim 15  wherein said polymorph V of torasemide contains no water.  
   
   
       21  Pharmaceutical form according to  claim 15  wherein said polymorph V of torasemide contains no solvent.  
   
   
       22 . The method according to  claim 14  wherein said polymorph V of torasemide contains no water.  
   
   
       23 . The method according to  claim 14  wherein said polymorph V of torasemide contains no solvent.  
   
   
       24 . The method according to  claim 14  polymorph V of torasemide is chemically pure.