硫酸软骨素注射剂质量状况评价与研究

Quality Evaluation of Chondroitin Sulfate Injections

目的考察硫酸软骨素注射剂的质量现状及存在问题,选取涉及产品有效性和安全性的关键质控项目进行研究,进一步完善质量标准。方法采用现行标准对抽验样品进行法定检验,查阅国内外标准及文献,赴生产企业实地调研,采用酶解液相色谱法、激光光散射法、反相色谱法及体积排阻色谱法等方法对该品种的质量状况进行全面评价。结果2016年硫酸软骨素注射剂国家评价性抽验结果表明,虽然法定标准检验结果均符合规定,但采用新的含量测定方法检测,多批次产品含量测定结果超出标准规定上限;标准中缺乏对相对分子质量的控制;二糖组成的测定结果提示,部分原料存在混入其他来源原料的风险;硫酸软骨素的抗凝血作用初步研究结果表明,不同来源的硫酸软骨素均具有抗凝血作用,鲨鱼来源的硫酸软骨素抗凝血作用最强。结论我国硫酸软骨素注射剂含量测定、相对分子质量与相对分子质量分布等检验项目亟待完善提高。

OBJECTIVE To investigate the quality status and problems of chondroitin sulfate injections and select the critical quality control items concerning the efficacy and safety to study in order to improve the quality standards.METHODS The statutory methods were adopted to test the samples.Many testing methods were established or improved on the basis of domestic and international standards and literature review and field research,including enzymatic HPLC,multiangle laser light scatter(MALLS),reverse phase chromatography,size exclusion chromatography,etc.RESULTS The national evaluation test in 2016 showed that all 41 batches of the samples met the requirements of current specifications.Exploratory studies showed that the assay results of the samples from some companies were obviously above the upper limit.The injection standard lacked control of molecular weight and molecular weight distribution.The disaccharide composition analysis suggested that in some bulk drug there was the risk of other origins of chondroitin sulfate sodium incorporation into the API.The study on the anticoagulatory effect of chondroitin sulfate sodium showed that chondroitin sulfate sodium from different origins had the action of anticoagulation.Chondroitin sulfate sodium from shark source had the most potensive anticoagulation effect.CONCLUSION Some items in the quality specification of chondroitin sulfate sodium injections are infeasible,including assay and molecular weight and molecular weight distribution need to be improved.