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中文摘要：
目的： 考察低分子肝素注射剂的质量现状及存在问题,对现行质量标准的科学性及检验方法进行研究。 方法： 采用现行标准对抽验样品进行法定检验;建立并完善了多个检验方法： （1）建立微量生色底物法测定抗Xa因子和抗IIa因子活性;（2）完善分子量与分子量分布校正曲线建立方法;（3）建立阴离子交换色谱法检查有关物质;（4）建立激光光散射法测定绝对分子量;（5）与进口原研厂制剂进行质量比对;（6）对生产企业进行实地调研。 结果： 个别样品不符合标准规定,分子量与分子量分布、抗Xa因子与抗IIa因子活性为主要的不合格项,各生产企业质量标准与产品质量差异大,国产低分子肝素与进口制剂差距较大;样品经亚硝酸降解后,杂质硫酸皮肤素和多硫酸软骨素分离度大于3.0,所有样品均未检出多硫酸软骨素,硫酸皮肤素含量小于2.0%;激光光散射法对低分子肝素分子量对照品的建立有重要意义;生产企业对关键质控项目的检验能力有待提高。 结论： 大部分国产低分子肝素注射剂能符合现行质量标准要求;现行标准未对低分子肝素进行分类管理,标准较低;作为仿制药,国产低分子肝素注射剂在产品质量与质量标准上均与国外原研厂有较大差距,亟待提高。
英文摘要：
Objective： To evaluate the quality status and problems of low molecular weight heparin injection and study the scientificity of the current quality standard and the test method. Methods： The statutory methods were used to test the samples.Several test methods for exploratory research were established and improved：（1）determination of the activity of anti-FXa and anti-FIIa by micro-chromogenic substrate methods;（2）improvement of the method to establish the calibration curve of molecular weight determination;（3）establishment of the high performance anion exchange chromatography（HPAEC）to determine relative substances;（4）establishment of the mutiangle laser light scatter（MALLS）method to determine the absolute molecular weight of low molecular weight heparin;（5）quality comparison between imported products and original research plant;（6）implementation of field researches to production enterprises. Results： There were individual samples which did not meet the standard requirements,and whose molecular weight distribution, anti-FXa and anti-F IIa activity were the major nonconforming items.Quality standards and product quality of the production enterprises had significant difference,and there was a great quality gap between the domestic low-molecular-weight heparins and the imported preparations.After the samples were degraded by nitrous acid,the separation of dermatan sulfate（DS）and oversulfated chondroitin sulfate（OSCS）was greater than 3.0;OSCS were not detected in any samples;DS contents were less than 2.0%.This test indicated that establishment of laser light scattering method was significant to calibrate the reference substance for the molecular weight of the low molecular weight heparin.The capability of key quality control inspection of production enterprise needed to be improved. Conclusion： Most of the domestic low molecular weight heparin injections can meet the requirements of the statutory specification.The statutory specification does not classify the low molec
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