多种聚氧乙烯脱水山梨醇单油酸酯致Beagle犬类过敏反应的试验研究

Anaphylactoid reactions induced by polysorbate 80 on Beagle dogs

目的:评价多种聚氧乙烯脱水山梨醇单油酸酯(吐温80)静脉给药对Beagle犬的致敏性。方法:Beagle犬随机分为5组,每组3只,分别静脉注射4种0.5%吐温80溶液,给药体积10mL.kg-1,前肢静脉恒速注射(速度5 mL.min-1)。观察给药前至给药后24 h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、给药过程中、停药后测量动物血压、心率。给药前及停药后10 min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:0.5%浓度样品3静脉滴注可诱发Beagle犬出现类过敏反应的典型症状,其他3种吐温80诱发犬出现类过敏反应的不典型症状;4种吐温80溶液均可导致Beagle犬出现不同程度的心率加快,血压下降;各组犬血浆组胺升高均未超过1倍以上。0.5%浓度样品2组犬的不典型类过敏反应症状、血压下降程度均较其他组吐温80受试液轻。综合判定,0.5%浓度样品3静脉注射给Beagle犬其类过敏反应为可疑,其他各组受试液均未能诱发Beagle犬出现典型的类过敏反应。结论:吐温80浓度在0.5%时,对过敏体质等特殊人群临床应用仍有一定风险,不可大意。生产工艺对吐温80的致敏性有一定影响,精制后吐温80的安全性有了一定提高,但仍有待进一步研究。

Objective： To evaluate the sensitization effect of polysorbate 80 from different factories on Beagle dogs. Method： Beagles dogs were randomly divided into 5 groups, 3 in each group, received respectively the intravenous infusion of polysorbate 80 made by four factories in the concentration of 0.5%, with the constant infusing speed of 5 mL·min^-1 and volume of 10 mL·kg^-1. Changes 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 pressure and heart rates were tested by the machine of Bp-98E, blood samples of animals were collected before infusion and at 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 histam ine level. Result： Typical symptoms of anaphylactoid reactions were found in sample 3 group, atypical symptoms were found in other polysorbate 80 groups. Different degrees of heart rate speeding and blood pressure downing were found in polysorbate 80 groups.No over 1-fold increase of plasma histamine level was found in all groups. The atypical anaphylactoid reactions and blood pressure of sample 2 group was lighter than other polysorbate 80 groups. Estimation showed that the sample 3 induced the suspicious anaphylactoid reactions, other test solutions did not induce the typical anaphylactoid reactions on Beagle dogs. Conclusion： For allergies and other special populations,there is still a certain risk to applicate polysorbate 80 in the concentration of 0.5%. Production process of polysorbate 80 have a certain influence on allergenicity, refined polysorbate 80 increase the security, but further reasearchs are needed to confirmed.