MESYLATE DIHYDRATE SALTS OF 5-(2-(4-(1,2-BENZISOTHIAZOL-3-YL)-1-PIPERAZINYL)-ETHYL)-6-CHLORO-1,3-DIHYDRO-2(1H)-INDOL-2-ONE(=ZIPRASIDONE), ITS PREPARATION AND ITS USE AS DOPAMINE D2 ANTAGONIST

摘要

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS: 1. A mesylate dihydrate salt of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)ethyl)-6-chloroo-1,3-dihydro-2H-indol-2-one. 2. The salt of claim 1 in the form of lath crystals. 3. The salt of claim 1 in the form of needle crystals. 4. A pharmaceutical composition for the treatment of a psychotic disorder comprising an amount of the salt of any one of claims 1 to 3 that is effective in the treatment of the psychotic disorder and a pharmaceutically acceptable carrier. 5. The composition of claim 4 wherein the disorder is schizophrenia, anxiety or migraine pain. 6. The composition of claim 4 wherein the disorder is schizophrenia. 7. The composition of claim 4, 5 or 6 which is adapted for parental administration. 8. The composition of claim 7, adapted for intramuscular injection. 9. A process for producing the needle crystals of the salt of claim 3 which comprises: mixing 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)ethyl)-6-chloro-1,3-dihydro-2H-indol-22-one free base with a mixture of water and an organic solvent, adding dilute methanesulfonic acid; heating the reflux while stirring; adding a seed crystal of the needle crystals; allowing a resulting solution to cool slowly with stirring; filtering and washing the needle crystals; and drying the needle crystals at ambient temperature. 10. A process for producing the lath crystals of the salt of claim 2 which comprises; mixing 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one free base with water; warming the resulting slurry to 50.degree.C to 55.degree.C; adding concentrated methanesulfonic acid and heating the resulting mixture to reflux for 1 to 6 hours; cooling the resulting solution to provide the lath crystals; stirring the resulting slurry at ambient temperature; filtering and washing the crystals; and drying the crystals at ambient temperature.