METHOD FOR SELECTIVE CRYSTALLIZATION OF 3-PYRIDYL-1-HYDROXYETHYLIDENE-1,1-BISPHOSPHONIC ACID SODIUM AS HEMIPENTAHYDRATE OR MONOHYDRATE

• Main Authors: BILLINGS DENNIS MICHAEL, CAZER FREDRICK DANA, PERRY GREGORY EUGENE, REDMAN-FUREY NANCY LEE
• Format: Patent
• Language: English; Japanese
• Published: 25.02.2016
• Subjects: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

PROBLEM TO BE SOLVED: To provide a method of preparing 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphonic acid (risedronate) sodium hemipentahydrate or monohydrate.SOLUTION: A process for producing a hydrate comprises the steps of: (a) providing an aqueous solution of 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphonic acid sodium; (b) heating the aqueous solution; (c) adding an alcohol to the aqueous solution; and (d) cooling the aqueous solution. The step (b) includes heating the aqueous solution to a temperature of 25-75°C. The step (d) includes cooling the aqueous solution at a cooling rate of 0.06 to 5°C/min. The alcohol is isopropanol.SELECTED DRAWING: None 【課題】３−ピリジル−１−ヒドロキシエチリデン−１．１−ビスホスホン酸（リセドロネート（リセドロン酸））ナトリウムの２．５水和物又は１水和物を調製する方法を提供する。【解決手段】（ａ）３−ピリジル−１−ヒドロキシエチリデン−１，１−ビスホスホン酸ナトリウムの水溶液を供給する工程、（ｂ）前記水溶液を加熱する工程、（ｃ）前記水溶液に、アルコールを加える工程、及び（ｄ）前記水溶液を冷却する工程を含む方法。工程（ｂ）において、２５〜７５℃の温度で前記水溶液を加熱すること、及び、工程（ｄ）において０．０６〜５℃／分の割合の冷却速度で前記水溶液を冷却することを含み、前記アルコールがイソプロパノールである、水和物を製造する方法。【選択図】なし