海洋多糖类药物藻酸双酯钠制剂质量状况评价和质量研究  

Quality evaluation and quality research of marine polysaccharide drug propylene glycol alginate sodium

作　　者：王悦 宋玉娟 陈欣桐 李振华 韩苗苗 邓利娟 范慧红 WANG Yue;SONG Yujuan;CHEN Xintong;LI Zhenhua;HAN Miaomiao;DENG Lijuan;FAN Huihong(Institute for Chemical Drug Control,National Institutes for Food and Drug Control,Beijing 102629,China;NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs,Beijing 102629,China)

机构地区：[1]中国食品药品检定研究院化学药品检定所,北京102629 [2]国家药品监督管理局化学药品质量研究与评价重点实验室,北京102629

出　　处：《中国海洋药物》2023年第5期1-9,共9页Chinese Journal of Marine Drugs

基　　金：青岛海洋科学与技术试点国家实验室海洋药物与生物制品功能实验室开放性课题(LMDBKF201806);重大新药创制“化药制剂质量评价关键技术研究”课题(2015ZX09303001);中国食品药品检定研究院学科带头人基金(2021X6)资助。

摘　　要：目的评价我国藻酸双酯钠制剂的质量情况,建立和提高质控方法,全面考察产品的结构、活性和安全性,整体提高我国首个海洋多糖类药物的质量控制水平。方法对国家抽检的样品进行全项检验,对检验结果进行统计分析。并根据该品种生产工艺,应用离子色谱、体积排阻色谱、多角度激光光散射技术、气相色谱法、活化部分凝血活酶时间(activated partial thromboplastin time,APTT)法等多种物理、化学、生物学方法对藻酸双酯钠原料和制剂的理化性质、活性及质量控制方法进行深入研究。确证了产品结构,建立了特征性鉴别、分子量与分子量分布、抗凝活性、工艺杂质等质控方法。结果12个生产厂家的173批片剂样品按照标准检验全部合格,4个生产厂家的33批注射剂样品1批不合格,不合格项目为可见异物。研究表明现行质量标准不能有效控制产品质量,质量研究采用不同分析技术分别建立了含量测定、分子量与分子量分布、有机硫含量和游离硫酸根含量、单糖组成和摩尔比值、异丙醇酯基取代程度、铵盐、残留溶剂、溶出度等分析方法,并拟定了原料和片剂、注射用粉针和注射液的标准草案。结论多种分析技术的应用增加了对藻酸双酯钠结构、杂质、理化性质和活性的认识和质量控制水平,拟定的国家标准草案与原标准相比有大幅提高。Objective To evaluate the quality of native drug propylene glycol alginate sodium sulfate(PSS),establish and improve the quality control methods,investigate the structure-activity relationship,and improve the quality standards of the first Marine polysaccharide drug in China.Methods All of the samples by national sampling evaluation were tested,and the results were statistically analyzed.Various methods had been used to study the physical and chemical properties,activity and quality control methods of PsS,such as ion chromatography,size-exclusive chromatography,multi-angle laser light scattering,gas chromatography and APTT methods.The methods such as M/G identification,molecular weight and molecular weight distribution,anticoagulant activity and impurities control were established.Results 173 batches of tablet samples from 12 manufacturers were all meet the quality standards,and 1 batch of 33 batches of injection samples which from 4 manufacturers was not meet the quality standard.The unqualified item was visible particles.Due to the current quality standard could not effectively control the drug quality,the assay,organic sulfur content,molecular weight and molecular weight distribution,and free sulfate content,composition and molar ratio of monosaccharide and propylene glycol ester group substitution degree,ammonium salt,residual solvents,dissolution and other analysis methods were established,Draft quality standards for active pharmaceutical ingredient(API)and tablets,injections of PSS were also established.Conclusion The application of various analytical techniques has increased the understanding of physical and chemical properties and activity of PSS and increase the quality control level of PSS.The draft national quality standards have been greatly improved compared with the original ones.

关 键 词：藻酸双酯钠 标准提高 国家标准 结构确证 多糖类药物 

分 类 号：R917[医药卫生—药物分析学]