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目的研究雷公藤内酯醇半合成衍生物(MC002)的理化性质和有关物质,为剂型设计提供依据。方法采用紫外分光光度法测定MC002在甲醇中的吸收系数;采用红外光谱仪测定MC002的红外吸收光谱;按中国药典2010版二部中溶解度的测定方法测定在不同溶剂中的近似溶解度;采用摇瓶法测定MC002在正辛醇-水、正辛醇-pH=7.4磷酸盐缓冲液中的油水分配系数;用Thiele管测定熔点;采用X-射线粉末衍射法测定其晶型。结果 MC002在甲醇中的吸收系数(E1%)为226.23±29.18;样品红外吸收光谱图与标准品谱图基本一致,易溶于水、甲醇、乙醇、丙酮,微溶于氯仿和乙酸乙酯,在乙醚中极微溶解;在正辛醇-水和正辛醇-pH=7.4磷酸盐缓冲液中的分配系数分别为0.074 0和1.080;熔点为50~52℃;X-射线粉末衍射说明MC002为非结晶型粉末。3批有关物质测定均<1%,样品纯度>99%。结论 MC002是一个亲水性很强的盐类药物,本实验确定的MC002部分理化性质和有关物质分析,可为其生物药剂学的研究及剂型设计提供依据。
Objective To study the physicochemical properties and related substances of triptolide derivatives (MC002), and to provide a basis for formulation design. Methods The absorption coefficient of MC002 in methanol was determined by ultraviolet spectrophotometry. The infrared absorption spectrum of MC002 was determined by infrared spectrophotometer. The approximate solubility of MC002 in different solvents was determined according to the method of solubility determination of the second edition of Chinese Pharmacopoeia 2010. The oil-water partition coefficient of MC002 in n-octanol-water, n-octanol-pH = 7.4 phosphate buffer was determined. The melting point was determined by Thiele tube. The crystal form was determined by X-ray powder diffraction. Results The absorption coefficient (E1%) of MC002 in methanol was 226.23 ± 29.18. The infrared absorption spectrum of the sample was basically the same as that of the standard sample. It was soluble in water, methanol, ethanol and acetone, slightly soluble in chloroform and ethyl acetate, Very slightly soluble in ether; partition coefficients in n-octanol-water and n-octanol-pH = 7.4 phosphate buffer were 0.074 0 and 1.080 respectively; melting point was 50-52 ° C .; X-ray powder diffraction showed that MC002 was Non-crystalline powder. 3 batches of relevant substances were determined <1%, sample purity> 99%. Conclusion MC002 is a highly hydrophilic salt medicine. The physical and chemical properties and related substances of MC002 determined in this experiment may provide the basis for its biopharmaceutical research and dosage form design.