Novel crude and crystalline forms of lercanidipine hydrochloride

Abstract

The invention describes novel lercanidipine crude Forms (A) and (B), novel lercanidipine hydrochloride crystalline Forms (I) and (II) obtained from said crude Forms, pharmaceutical, antihypertensive compositions containing as active agent at least one of the lercanidipine hydrochloride crystalline Forms (I) and (II) and methods of use thereof

1 - 72 . (canceled)  
     
     
         73 . A method of treating a subject with hypertension, coronary heart disease or congestive heart failures the method comprising administering to said subject a therapeutically effective amount of crystalline lercanidipine hydrochloride Form I having at least one significant X-ray powder diffraction pattern peak at a 2θ value selected from the group consisting of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8.  
     
     
         74 . A method of treating or preventing atherosclerotic lesions in arteries in a subject, the method comprising administering to said subject a therapeutically effective amount of crystalline lercanidipine hydrochloride Form I having at least one significant X-ray powder diffraction pattern peak at a 2θ value selected from the group consisting of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8.  
     
     
         75 . A method of treating or preventing heart failure in a subject, the method comprising administering to said subject a therapeutically effective amount of crystalline lercanidipine hydrochloride Form I having at least one significant X-ray powder diffraction pattern peak at a 2θ value selected from the group consisting of 5.4. 14.2 18.6. 21.7 21.9. and 22.8.  
     
     
         76 . The method of  claim 73  wherein said subject is a human.  
     
     
         77 - 84 . (canceled)  
     
     
         85 . The method of  claim 74  wherein said subject is a mammal.  
     
     
         86 . The method of  claim 75  wherein said subject is a mammal.  
     
     
         87 . The method of  claim 73  further comprising administering amorphous lercanidipine hydrochloride to said subject.  
     
     
         88 . The method of  claim 74  further comprising administering amorphous lercanidipine hydrochloride to said subject.  
     
     
         89 . The method of  claim 75  further comprising administering amorphous lercanidipine hydrochloride to said subject.  
     
     
         90 . The method of  claim 73  wherein the crystalline lercanidipine hydrochloride Form I has at least three significant X-ray powder diffraction pattern peaks at 2θ values selected from the group consisting of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8.  
     
     
         91 . The method of  claim 90  wherein the crystalline lercanidipine hydrochloride Form I has significant X-ray powder diffraction pattern peaks at 2θ values of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8.  
     
     
         92 . The method of  claim 74  wherein the crystalline lercanidipine hydrochloride Form I has at least three significant X-ray powder diffraction pattern peaks at 20 values selected from the group consisting of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8.  
     
     
         93 . The method of  claim 92  wherein the crystalline lercanidipine hydrochloride Form I has significant X-ray powder diffraction pattern peaks at 2θ values of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8.  
     
     
         94 . The method of  claim 75  wherein the crystalline lercanidipine hydrochloride Form I has at least three significant X-ray powder diffraction pattern peaks at 2θ values selected from the group consisting of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8.  
     
     
         95 . The method of  claim 94  wherein the crystalline lercanidipine hydrochloride Form I has significant X-ray powder diffraction pattern peaks at 2θ values of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8.  
     
     
         96 . An antihypertensive composition comprising a crystalline lercanidipine hydrochloride Form I having at least one significant X-ray powder diffraction pattern peak at a 2θ value selected from the group consisting of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8 and amorphous lercanidipine hydrochloride.  
     
     
         97 . The antihypertensive composition of  claim 96  wherein the composition is substantially free of crystalline lercanidipine hydrochloride Form II having at least one significant X-ray powder diffraction peak at a 2θ value selected from the group consisting of 9.5, 14.7, 16.1, 19.1, 20.8, 23.4, 23.6, 24.8 and 25.2.  
     
     
         98 . The antihypertensive composition of  claim 96  wherein said lercanidipine hydrochloride Form I has at least three significant X-ray powder diffraction pattern peaks at 2θ values selected from the group consisting of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8.  
     
     
         99 . The antihypertensive composition of  claim 98  wherein the composition is substantially free of crystalline lercanidipine hydrochloride Form II having at least one significant X-ray powder diffraction peak at a 20 value selected from the group consisting of 9.5, 14.7, 16.1, 19.1, 20.8, 23.4, 23.6, 24.8 and 25.2.  
     
     
         100 . The antihyperstive composition of  claim 96  wherein said lercanidipine hydrochloride Form I has significant X-ray powder diffraction pattern peaks at 2θ values of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8.  
     
     
         101 . The antihypertensive composition of  claim 100  wherein the composition is substantially free of crystalline lercanidipine hydrochloride Form II having at least one significant X-ray powder diffraction peak at a 2θ value selected from the group consisting of 9.5, 14.7, 16.1, 19.1, 20.8, 23.4, 23.6, 24.8 and 25.2.  
     
     
         102 . A method of treating a subject with hypertension, coronary heart disease or congestive heart failure, the method comprising administering to said subject a therapeutically effective amount of a lercanidipine mixture comprising crystalline lercanidipine hydrochloride Form I having at least one significant X-ray powder diffraction pattern peak at a 2θ value selected from the group consisting of 5.4, 14.2, 18.6, 21.7, 21.9, and 22.8 and amorphous lercanidipine hydrochloride.