实验设计法优化高浓度静注人免疫球蛋白制剂的处方  

Optimization of formula of high concentration human immunoglobulin for intravenous injection by design of experiment

作　　者：刘亚芳 李冠军 罗坚[2] 张伦 张剑涛 梁雪爽 马小伟 张学成 LIU Ya-fang;LI Guan-jun;LUO Jian;ZHANG Lun;ZHANG Jian-tao;LIANG Xue-shuang;MA Xiao-wei;ZHANG Xue-cheng(Research and Development Center,Hualan Biological Engineering Inc.,Xinxiang 453003,Henan Province,China)

机构地区：[1]华兰生物工程股份有限公司研发中心,河南新乡453003 [2]中国科学院过程工程研究所,北京100190

出　　处：《中国生物制品学杂志》2020年第4期445-448,454,共5页Chinese Journal of Biologicals

摘　　要：目的通过实验设计法优化高浓度(10%)静注人免疫球蛋白(human immunoglobulin for intravenous injection,IVIG)的制剂处方。方法采用单因素试验(包括等电点、二级结构、分子大小分布,转变中点温度4个指标)确定IVIG(10%)的pH范围,同时经国外相关数据和产品质量指标选择IVIG的稳定剂甘氨酸和聚山梨酯80的浓度范围,再采用实验设计法优化IVIG的pH及稳定剂浓度。以转变中点温度为指标,通过单因素试验优化IVIG(10%)的离子强度。结果最佳IVIG(10%)制剂处方为聚山梨酯80:80 mg/L,pH:4. 5,甘氨酸:0. 25 mol/L。最适离子强度为0 mmol/L氯化钠。结论成功优化了IVIG(10%)的制剂处方,可确保制剂的稳定性,提高临床用药安全性。Objective To optimize the formula of high concentration(10%) human immunoglobulin for intravenous injection(IVIG)by design of experiment(DOE). Methods The range of pH value of IVIG(10%)was determined by a single factor experiment including four indicators,i. e. isoelectric point,secondary structure,molecular size distribution and change midpoint temperature. Meanwhile,the concentration ranges of glycine and polysorbate 80 as stabilizers were determined by the foreign related data and product quality indicators,and the ion strength of IVIG(10%) by a single factor experiment using change midpoint temperature as an indicator. Results The optimal formula of IVIG(10%)was as follows:polysorbate 80:80 mg/L;pH:4. 5;glycine:0. 25 mol/L. The optimal ion strength was 0 mmol/L sodium chloride. Conclusion The formula of IVIG(10%)was successfully optimized,which ensured the stability of the product and enhanced the safety in clinical application.

关 键 词：静注人免疫球蛋白 聚山梨酯80 pH 甘氨酸 离子强度 

分 类 号：R457.2[医药卫生—治疗学]