Carvedilol hydrobromide
View Patent ↗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-(o-methoxyphenoxy)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 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±0.2 (2θ), 21.9±0.2 (2θ), 25.2±0.2 (2θ), and 30.6±0.2 (2θ).
2. A compound which is carvedilol hydrobromide monohydrate having an x-ray diffraction pattern as substantially shown in FIG. 1 .
3. A compound which is carvedilol hydrobromide monohydrate having an infrared spectrum, which comprises characteristic absorption bands expressed in wave numbers as substantially shown in FIG. 6 .
4. A compound which is carvedilol hydrobromide monohydrate having a Raman spectrum, which comprises characteristic peaks as shown in FIG. 3 .
5. A compound which is carvedilol hydrobromide dioxane solvate 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).
6. A compound which is carvedilol hydrobromide dioxane solvate having an x-ray diffraction pattern as substantially shown in FIG. 78 .
7. A compound which is carvedilol hydrobromide 1-pentanol solvate 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).
8. A compound which is carvedilol hydrobromide 1-pentanol solvate having an x-ray diffraction pattern as substantially shown in FIG. 79 .
9. A compound which is carvedilol hydrobromide 2-methyl-1-propanol solvate 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).
10. A compound which is carvedilol hydrobromide 2-methyl-1-propanol solvate having an x-ray diffraction pattern as substantially shown in FIG. 80 .
11. A compound which is carvedilol hydrobromide trifluoroethanol solvate 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).
12. A compound which is carvedilol hydrobromide trifluoroethanol solvate having an x-ray diffraction pattern as substantially shown in FIG. 81 .
13. A compound which is carvedilol hydrobromide 2-propanol solvate 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).
14. A compound which is carvedilol hydrobromide 2-propanol solvate having an x-ray diffraction pattern as substantially shown in FIG. 82 .
15. A compound which is carvedilol hydrobromide n-propanol solvate #1 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).
16. A compound which is carvedilol hydrobromide n-propanol solvate #1 having an x-ray diffraction pattern as substantially shown in FIG. 46 .
17. A compound which is carvedilol hydrobromide n-propanol solvate #2 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).
18. A compound which is carvedilol hydrobromide n-propanol solvate #2 having an x-ray diffraction pattern as substantially shown in FIG. 54 .
19. A compound which is carvedilol hydrobromide ethanol solvate 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).
20. A compound which is carvedilol hydrobromide ethanol solvate having an x-ray diffraction pattern as substantially shown in FIG. 70 .
21. A compound which is carvedilol hydrobromide anhydrous 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).
22. A compound which is carvedilol hydrobromide anhydrous having an x-ray diffraction pattern as substantially shown in FIG. 62 .
23. A compound which is carvedilol hydrobromide anhydrous having an infrared spectrum, which comprises characteristic absorption bands expressed in wave numbers as substantially shown in FIG. 67 .
24. A compound which is carvedilol hydrobromide anhydrous having a Raman spectrum, which comprises characteristic peaks as substantially shown in FIG. 64 .
25. A pharmaceutical composition, comprising the compound according to claim 1 and a pharmaceutically acceptable carrier.
26. A pharmaceutical composition, comprising the compound according to claim 21 and a pharmaceutically acceptable carrier.
27. 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 .
28. 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 21 .
29. 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 25 .
30. 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 26 .