Carvedilol hydobromide

Abstract

The present invention relates to a salt of carvedilol, corresponding compositions containing such a carvedilol salt or corresponding solvates thereof, and/or methods of using the aforementioned compound(s) in the treatment of certain disease states in mammals, in particular man. The present invention further relates to a novel crystalline form of carvedilol hydrobromide, which is the hydrobromide salt of 1-(carbazol-4-yloxy)-3-[[2-(omethoxyphenoxyl)ethyl]amino]-2-propanol, and/or other carvedilol solvates thereof, compositions containing salts or solvates of carvedilol hydrobromide, and methods of using the aforementioned compound(s) to treat hypertension, congestive heart failure, and angina, etc.

1 . A compound which is carvedilol hydrobromide monohydrate.  
   
   
       2 . The compound according to  claim 1  having an x-ray diffraction pattern as substantially shown in  FIG. 1 .  
   
   
       3 . The compound according to  claim 2  having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 6.5±0.2 (2θ), 10.3±0.2 (2θ), 15.7±0.2 (2θ), 16.3±0.2 (2θ), 19.8±0.2 (2θ), 20.1±02 (2θ), 25.2±0.2 (2θ), and 30.6±0.2 (2θ).  
   
   
       4 . The compound according to  claim 1  having an infrared spectrum, which comprises characteristic absorption bands expressed in wave numbers as substantially shown in  FIG. 6 .  
   
   
       5 . The compound according to  claim 1  having a Raman spectrum, which comprises characteristic peaks as shown in  FIG. 3 .  
   
   
       6 . A compound which is carvedilol hydrobromide dioxane solvate.  
   
   
       7 . The compound according to  claim 6  having an x-ray diffraction pattern as substantially shown in  FIG. 78 .  
   
   
       8 . The compound according to  claim 7  having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 7.7±0.2 (2θ), 8.4±0.2 (2θ), 15.6±0.2 (2θ), 17.0±0.2 (2Θ), 18.7±0.2 (2Θ), 19.5±0.2 (2θ), 21.4±0.2 (2θ), 23.7±0.2 (2θ), and 27.9±0.2 (2θ).  
   
   
       9 . A compound which is carvedilol hydrobromide 1-pentanol solvate.  
   
   
       10 . The compound according to  claim 9  having an x-ray diffraction pattern as substantially shown in  FIG. 79 .  
   
   
       11 . The compound according to  claim 10  having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 7.5±0.2 (2θ), 7.8±0.2 (2θ), 15.2±0.2 (2θ), 18.9±0.2 (2θ), 22.1±0.2 (2θ), and 31.4±0.2 (2θ).  
   
   
       12 . A compound which is carvedilol hydrobromide 2-methyl-1-propanol solvate.  
   
   
       13 . The compound according to  claim 12  having an x-ray diffraction pattern as substantially shown in  FIG. 80 .  
   
   
       14 . The compound according to  claim 13  having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 7.8±0.2 (2θ), 8.1±0.2 (2θ), 16.3±0.2 (2θ), 18.8±0.2 (2θ), 21.8±0.2 (2θ), and 28.5±0.2 (2θ).  
   
   
       15 . A compound which is carvedilol hydrobromide trifluoroethanol solvate.  
   
   
       16 . The compound according to  claim 15  having an x-ray diffraction pattern as substantially shown in  FIG. 81 .  
   
   
       17 . The compound according to  claim 16  having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 7.7±0.2 (2θ) 8.4±0.2 (2θ), 15.6±0.2 (2θ), 16.9±0.2 (2θ), 18.9±0.2 (2θ), 21.8±0.2 (2θ), 23.3±0.2 (2θ), 23.8±0.2 (2θ), and 32.7±0.2 (2θ).  
   
   
       18 . A compound which is carvedilol hydrobromide 2-propanol solvate.  
   
   
       19 . The compound according to  claim 18  having an x-ray diffraction pattern as substantially shown in  FIG. 82 .  
   
   
       20 . The compound according to  claim 19  having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 7.9±0.2 (2θ), 8.3±0.2 (2θ), 18.8±0.2 (2θ), 21.7±0.2 (2θ), 23.2±0.2 (2θ), 23.6±0.2 (2θ), and 32.1±0.2 (2θ).  
   
   
       21 . A compound which is carvedilol hydrobromide n-propanol solvate #1.  
   
   
       22 . The compound according to  claim 21  having an x-ray diffraction pattern as substantially shown in  FIG. 46 .  
   
   
       23 . The compound according to  claim 22  having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 7.9±0.2 (2θ), 8.5±0.2 (2θ), 17.0±0.2 (2θ), 18.8±0.2 (2θ), 21.6±0.2 (2θ), 23.1±0.2 (2θ), 23.6±0.2 (2θ), and 21.2±0.2 (2θ).  
   
   
       24 . A compound which is carvedilol hydrobromide n-propanol solvate #2.  
   
   
       25 . The compound according to  claim 24  having an x-ray diffraction pattern as substantially shown in  FIG. 54 .  
   
   
       26 . The compound according to  claim 25  having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 8.0±0.2 (2θ), 18.8±0.2 (2θ), 21.6±0.2 (2θ), 23.1±0.2 (2θ), 25.9±0.2 (2θ), 27.2±0.2 (2θ), 30.6±0.2 (2θ), and 32.2±0.2 (2θ).  
   
   
       27 . A compound which is carvedilol hydrobromide ethanol solvate.  
   
   
       28 . The compound according to  claim 27  having an x-ray diffraction pattern as substantially shown in  FIG. 70 .  
   
   
       29 . The compound according to  claim 28  having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 8.1±0.2 (2θ), 8.6±0.2 (2θ), 13.2±0.2 (2θ), 17.4±0.2 (2θ), 18.6±0.2 (2θ), 21.8±0.2 (2θ), 23.2±0.2 (2θ), 23.7±0.2 (2θ), and 27.4±0.2 (2θ).  
   
   
       30 . A compound which is carvedilol hydrobromide anhydrous.  
   
   
       31 . The compound according to  claim 30  having an x-ray diffraction pattern as substantially shown in  FIG. 62 .  
   
   
       32 . The compound according to  claim 31  having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 6.6±0.2 (2θ), 16.1±0.2 (2θ), 17.3±0.2 (2θ), 21.2±0.2 (2θ), 22.1±0.2 (2θ), 24.1±0.2 (2θ), and 27.9±0.2 (2θ).  
   
   
       33 . The compound according to  claim 30  having an infrared spectrum, which comprises characteristic absorption bands expressed in wave numbers as substantially shown in  FIG. 67 .  
   
   
       34 . The compound according to  claim 30  having a Raman spectrum, which comprises characteristic peaks as substantially shown in  FIG. 64 .  
   
   
       35 . A pharmaceutical composition, comprising the compound according to  claim 1  and a pharmaceutically acceptable carrier.  
   
   
       36 . A pharmaceutical composition, comprising the compound according to  claim 30  and a pharmaceutically acceptable carrier.  
   
   
       37 . A method of treating hypertension, congestive heart failure, or angina, which comprises administering to a subject in need thereof an effective amount of a compound according to  claim 1 .  
   
   
       38 . A method of treating hypertension, congestive heart failure, or angina, which comprises administering to a subject in need thereof an effective amount of a compound according to  claim 30 .  
   
   
       39 . A method of treating hypertension, congestive heart failure, or angina, which comprises administering to a subject in need thereof an effective amount of a pharmaceutical composition according to  claim 35 .  
   
   
       40 . A method of treating hypertension, congestive heart failure, or angina, which comprises administering to a subject in need thereof an effective amount of a pharmaceutical composition according to  claim 36.