基于小鼠耳廓蓝染实验评价静注人免疫球蛋白(pH4.0)类过敏反应

Evaluation of anaphylactoid reactions induced by human immunoglobulin for intravenous injection(pH 4.0)based on mouse auricular blue staining experiments

目的采用小鼠耳廓蓝染实验评价静注人免疫球蛋白(pH4.0)的类过敏反应,考察不同多聚体含量的产品引发类过敏反应的情况。方法分别选取含有不同多聚体含量的3批产品,A(1.3%)、B(0.1%)、C(0.5%),另通过加热制备多聚体含量升高的产品作为对照(C产品50℃水浴分别加热10 min、20 min),以小鼠注射给药后的症状以及耳廓蓝染率、蓝染评分、伊文思蓝渗出量作为类过敏评价指标。结果不同多聚体含量的产品引发类过敏反应症状有明显差异,耳廓蓝染率、蓝染评分以及EB渗出量差异具有统计学意义。同时产品加热后,随着多聚体含量不断升高,类过敏反应症状愈发严重。结论小鼠耳廓蓝染实验可用于初步评价不同多聚体含量产品的类过敏反应,对静注人免疫球蛋白(p H4.0)的质量控制及安全评价具有指导意义。

Objective To evaluate the anaphylactoid reactions induced by human immunoglobulin for intravenous injection(pH4.0)via the mouse auricular blue staining experiments,and to investigate the anaphylactoid reactions induced by products with different proportions of polymers.Methods Three batches of products with different proportions of polymers,A(1.3%),B(0.1%)and C(0.5%),were selected respectively,and products with increased proportions of polymers were prepared by heating as the control(product C was heated in the water bath at 50℃for 10 min and 20 min respectively).The symptoms of these mice after administration,the auricular blue staining rate,blue staining score,and Evans blue exudation were used as indicators for evaluation of anaphylactoid reactions.Results There were considerable differences in the symptoms of anaphylactoid reactions caused by products with different proportions of polymers,and there were statistically significant differences in the auricular blue staining rate,blue staining score,and Evans blue exudation.After the products were heated,the symptoms of anaphylactoid reactions deteriorated with the increase of proportions of polymers.Conclusion The mouse auricle blue staining experiment can be used to preliminarily evaluate the anaphylactoid reactions of products with different proportions of polymers,which can provide reference for quality control and safety evaluation of human immunoglobulin for intravenous injection(pH4.0).