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    • 1. 发明授权
    • Compositions of allosteric hemoglobin modifiers and methods of making the same
    • 变构血红蛋白修饰剂的组成及其制备方法
    • US07847120B2
    • 2010-12-07
    • US11112389
    • 2005-04-22
    • Al QuickAntonio M. SantosAlexandre J G G CarvalhoDouglas G. JohnsonJeffrey B. EtterChristopher Murray
    • Al QuickAntonio M. SantosAlexandre J G G CarvalhoDouglas G. JohnsonJeffrey B. EtterChristopher Murray
    • C07C229/00C07C65/03
    • A61K31/195
    • The present invention provides novel compositions of allosteric hemoglobin modifiers which are substantially free of impurities, specifically polymeric impurities. In one embodiment, the novel compositions contain an allosteric hemoglobin modifier compound and less than 100 ppm of the polymeric impurities generated during the preparation of this compound. Included in the present invention are novel methods for preparing allosteric hemoglobin modifiers that are substantially free of polymeric impurities. Also included in the present invention are improved methods for the purification of the product formed by the method of this invention. The novel methods of purification comprise extracting the crude composition with a water immiscible or partially immiscible solvent such as methylisobutyl ketone (MIBK) to lower amounts of impurities, specifically polymeric impurities. Also included are methods to reduce impurities by recrystallization of the crude synthesized product, followed by filtration of the recrystallized product. The present invention also includes the products made by the processes of the invention and methods for analyzing compositions comprised of these products.
    • 本发明提供基本上不含杂质,特别是聚合物杂质的变构血红蛋白改性剂的新型组合物。 在一个实施方案中,新型组合物含有变构血红蛋白改性剂化合物,并且在制备该化合物期间产生小于100ppm的聚合物杂质。 本发明包括制备基本上不含聚合物杂质的变构型血红蛋白改性剂的新方法。 本发明还包括用于纯化通过本发明方法形成的产品的改进方法。 新颖的纯化方法包括用与水不混溶或部分不混溶的溶剂如甲基异丁基酮(MIBK)提取粗组合物以降低杂质量,特别是聚合物杂质。 还包括通过粗合成产物的重结晶减少杂质的方法,然后过滤重结晶产物。 本发明还包括通过本发明的方法制备的产品和用于分析由这些产品组成的组合物的方法。