抗肿瘤雷公藤内酯醇半合成衍生物理化性质及其有关物质的研究  

Physicochemical properties and related substances of MC002

作　　者：魏宝红[1] 叶静[1] 王莉[2] 曹艳玲[3] 刘晓亚[1] 李志慧[1] 薛宝娟[1] 韦灵玉[1] 张玉杰[1] 

机构地区：[1]北京中医药大学中药学院,北京100102 [2]北京美迪克斯生物技术有限公司,北京100012 [3]哈尔滨商业大学生命科学与环境研究中心,哈尔滨150028

出　　处：《中南药学》2014年第6期567-570,共4页Central South Pharmacy

基　　金：国家重大新药创制科技重大专项课题(No.2009ZX0910214)

摘　　要：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 investigate the physicochemical properties and related substances of MC002 and provide evidences for the form of the drug. Methods UV was used to determine the absorption coefficient of MC002 in methanol; IR was used to obtain the infrared spectroscopy of MC002. We adopted the method from Ch.P（2010） to determine the solubility of MC002; Oil-water partition coefficient was studied with n-octyl alcohol-buffer system and pH = 7.4 PBS. Thiele-tube was used to determine the melting point of MC002; MC002 was characterized by powder X-ray diffraction（PXRD）. Results The absorption coefficient of MC002 in the methanol was 226.23±29.18; MC002 was soluble in water, methanol, ethanol and acetone; slightly soluble in chloroform and ethyl acetate; and very slightly soluble in ether; Oil-water partition coefficient in n-octanol-buffer system and pH =7.4 PBS was 0.074 0 and 1.080. The melting point was 50-52 ℃; PXRD showed that MC002 was non-crystalline powder. The concentration of related substances was 1%, and the purity was 99%. Conclusion MC002 is a salt with strong hydrophilicity. The study determines the physicochemical properties of MC002, to investigate its biopharmaceutics and drug form.

关 键 词：雷公藤内酯醇半合成衍生物 理化性质 有关物质 

分 类 号：TQ460.72[医药卫生—药物分析学] R917[化学工程—制药化工]