Crystalline Forms of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride
First Claim
Patent Images
1. A crystalline Form A of (−
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα
radiation at 15.1±
0.2, 16.0±
0.2, 18.9±
0.2, 20.4±
0.2, 22.5±
0.2, 27.3±
0.2, 29.3±
0.2 and 30.4±
0.2.
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Abstract
A hitherto unknown crystalline form of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence.
4 Citations
28 Claims
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1. A crystalline Form A of (−
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα
radiation at 15.1±
0.2, 16.0±
0.2, 18.9±
0.2, 20.4±
0.2, 22.5±
0.2, 27.3±
0.2, 29.3±
0.2 and 30.4±
0.2. - View Dependent Claims (2, 3, 4)
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα
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5. A process for producing a (−
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A, said process comprising;
dissolving a (−
)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B in acetone, acetonitrile or isopropanol to form a solution;leaving the solution to crystallize and isolating crystals of (−
)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A. - View Dependent Claims (6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A, said process comprising;
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18. A process for producing crystalline Form A of (−
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride comprising the step of cooling (−
)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-hydrochloride phenol of Form B for a time between 24 hours and 168 hours at a temperature of between −
4°
C. and −
80°
C. - View Dependent Claims (19, 20, 21, 22, 23, 24)
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride comprising the step of cooling (−
-
25. A crystalline Form A of (−
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride produced by the process of;
dissolving (−
)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B in acetonitrile together with active carbon,heating the solution to the boiling point, removing the active carbon by filtering, stirring the solution at a temperature below 40°
C.,removing insoluble residue by filtering and removing part of the solvent, leaving (−
)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize,redissolving the resulting crystals in acetonitrile, removing insoluble residue by filtering and removing part of the solvent, and leaving (−
)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize.
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride produced by the process of;
-
26. A pharmaceutical composition comprising, as an active ingredient, a crystalline Form A of (−
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα
radiation at 15.1±
0.2, 16.0±
0.2, 18.9±
0.2, 20.4±
0.2, 22.5±
0.2, 27.3±
0.2, 29.3±
0.2 and 30.4±
0.2, and at least one suitable additive or auxiliary substance.
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα
-
27. A pharmaceutical composition comprising, as an active ingredient, a crystalline Form A of (−
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride produced by the process of
dissolving (−
)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B in acetonitrile together with active carbon,heating the solution to the boiling point, removing the active carbon by filtering, stirring the solution at a temperature below 40°
C.,removing insoluble residue by filtering and removing part of the solvent, leaving (−
)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize,redissolving the resulting crystals in acetonitrile, removing insoluble residue by filtering and removing part of the solvent, and leaving (−
)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize, andat least one suitable additive or auxiliary substance.
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride produced by the process of
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28. A method of treating or inhibiting pain or urinary incontinence, said method comprising the step of administering a pharmaceutically effective amount of a crystalline Form A of (−
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα
radiation at 15.1±
0.2, 16.0±
0.2, 18.9±
0.2, 20.4±
0.2, 22.5±
0.2, 27.3±
0.2, 29.3±
0.2 and 30.4±
0.2 to a subject in need thereof.
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα
Specification