生脉注射液工艺改进前后类过敏反应比较

Comparative study on pseudoanaphylactoid reactions induced by pulse-activating injection before and after improving technology

目的:比较生脉注射液工艺改进前后对动物的类过敏反应的差异,以探讨提高生脉注射液安全性的可能性。方法:小鼠耳廓血管通透性分析:将ICR小鼠随机分成不同实验组,分别一次性静脉注射含有0.4%伊文思蓝(EB)的5%葡萄糖注射液、Compound 48/80溶液或工艺改进前后的不同浓度生脉注射液。给药后30 min记录各组动物耳廓血管通透性增高反应的阳性率,进行耳廓蓝染程度评分,并定量测定耳廓伊文思蓝渗出量。大鼠皮肤血管通透性试验:即动物先静脉注射给予0.6%伊文思蓝生理盐水溶液,10 min后再从背部皮内注射给予上述受试物,每个点注射50μL药液,20 min后处死大鼠,测量皮肤内的蓝色斑点大小,并定量测定其中伊文思蓝渗出量。结果:生脉注射液原工艺16.7 mL.kg-1组(相当于临床剂量的1.67倍剂量)的小鼠可见耳廓血管通透性明显增高,而10 mL.kg-1的生脉注射液(相当于临床等倍剂量)组未见明显的耳廓血管通透性增高;新工艺16.7 mL.kg-1组的耳廓通透性增高程度较相同剂量原工艺组明显减轻。原工艺生脉注射液皮内注射后,在注射部位导致明显的渗出、水肿,从而形成较大的蓝斑,有一定剂量关系。新工艺在注射局部也可造成一定程度的蓝斑,但蓝斑直径较原工艺组减小,皮肤伊文思蓝渗出量减少,说明新工艺的皮肤类过敏反应较轻。结论:生脉注射液原工艺有明显增高血管通透性的作用,提示有致类过敏作用;改进工艺后其导致血管通透性增高的不良作用减轻,提示改进工艺可减轻类过敏反应。

Objective： To investigate a possibility to improve the security of pulse-activating injection by comparing the differ- ence of pseudoanaphylactoid reactions （PR） induced by pulse-activating injection before and after improving technology. Method： The analysis of vascular permeability of the mice＇s ears： ICR mouse were divided into different test groups, and intravenously injected with solutions of different concentration of pulse-activating injection before and after improving technology, positive control Compound 48/80 and 5% glucose injection. All test substances were mixed with 0. 4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after injection. The vascular permeability of the rat＇s skin： the rats were intravenous injected with 0. 6% Evans blue normal saline solution first, 10 minutes later, the same test substances were intradermal injected into the back of rats, there are 16 injected spots in the back of rat. The rats were sacrificed and the diameter of locus ceruleus and the content of Evans blue leaked out were measured 20 min after injection. Result： Pulse-activating injection before improving technology with dose of 16. 7 mL . kg^-1 （ in 1.67 times the clinical dose ） caused obvious vascular hyperpermeability in ICR mice. In the group of pulse-activating injection before improving technology with dose of 10 mL .kg^-l（ in clinic equivalent dose）, no obvious vascular hyperpermeability in the ears were observed. The degrees of vascular hyperpermeability in the group of pulse-activating injection after improving technology with dose of 16.7 mL . kg^-1 were more lessen than the same dose of injection before improving technology. Pulse-activating injection before improving technology caused obvious exudation, oedema locus ceruleus in the injection site of rat＇s back, and it showed a certain dose-effect relation. Pulse-activating injection after improving technology caused locus ceruleus in the injection site too, but the diame- ters of the locus ceruleus were shorter than the diameters in the group of pulse-activating injection before improving technology, and the contents of leaked out Evans blue were fewer. All of these showed that PR of skin induced by pulse-activating injection after improving technology is alleviated. Conclusion： Pulse-activating injection before improving technology cause obvious vascular hyperpermeability, but the same dose of pulse-activating injection after improving technology can＇t cause obvious vascular hyperpermeability. The result in- dicated that the pulse-activating injection before improving technology can cause PR, improving technology can lessen the degree of PR induced by the injection.