聚山梨酯80及其配制的鱼腥草注射液致Beagle犬类过敏反应实验研究

Anaphylactoid Reactions Inducing Effect of Polysorbate 80 and Polysorbate 80 Contained Houttuynia Cordata Injection on Beagle

目的评价多种聚山梨酯80及其配制的鱼腥草注射液静脉给药对Beagle犬的致敏性。方法 Beagle犬是类过敏反应的敏感动物,以动物反应症状与血浆组胺升高为判断标准,综合判定类过敏反应。Beagle犬随机分为18组,每组3只,分别静脉注射不同厂家0.25%、0.10%、0.05%浓度的聚山梨酯80灭菌水溶液,或分别含0.25%、0.30%不同厂家聚山梨酯80的鱼腥草注射液。给药体积10mL/kg,前肢静脉恒速注射(速度5mL/min)。观察给药前至给药后24h每只犬的变化,记录症状出现、消失时间,并根据反应症状的轻重判定级别。给药前及停药后10min取血,ELISA方法检测血浆组胺含量,并结合反应症状级别,综合判定致敏性。结果各厂家、各浓度(0.05%、0.10%、0.25%)聚山梨酯80灭菌液以及各组鱼腥草注射液,均未导致Beagle犬出现典型的类过敏反应症状及血浆组胺升高1倍以上。综合判定,各组受试液均未诱发Beagle犬出现典型的类过敏反应。结论控制聚山梨酯80质量,并将使用浓度限定在0.30%或0.25%以下,可以在保证药物增溶效果的同时避免类过敏反应的发生。

Objective To evaluate the sensitization effect of polysorbate 80 and polysorbate 80 contained Houttuynia cordata Injection in different concentrations on Beagle. Methods Beagles,a kind of animal highly sensitive to sensitizing agents,were randomly divided into 18 groups,3 in each group. They received respectively the intravenous infusion of polysorbate 80 made by different factories in different concentrations （0.25%,0.10%,0.05%）,and Houttuynia cordata Injection containing polysorbate 80 in concentration of 0.25% or 0.30%,with the constant infusing speed of 5 mL/min and volume of 10 mL/kg. Changes of animals＇ condition were observed before infusion and in the 24 h after infusion,time of symptom appearance and disappearance was recorded,and the grade of response was determined. Moreover,blood samples of animals were collected before infusion and 10 min after ending infusion for measuring histamine content in plasma using ELISA. Then the sensitization effect was comprehensively estimated by combined consideration of the responding grade and histamine level. Results No typical symptom of anaphylactoid reaction and over 1-fold increase of histamine level was found in all groups that received intravenous infusion of polysorbate 80 or polysorbate 80 contained Houttuynia cordata Injection in different concentrations. Estimation showed that all test solutions didn＇t induce typical anaphylactoid reaction on Beagle. Conclusions Considering both the appearance of symptoms and the elevation of blood content of histamine could be taken as the criteria for comprehensive diagnosis of anaphylactoid reactions. The solubilization effect and safety （for foreclose anaphylactoid reaction） of polysorbate 80 could be ensured by controlling its quality and concentration below 0.25% or 0.30%.