补体活化的体外评价模型建立及应用

发布时间：2018-05-25 13:42

本文选题：过敏反应 + 补体　；参考：《药学学报》2017年05期

【摘要】：补体激活相关的假性过敏反应(complement activation-related pseudo-allergic reactions,CARPA)占全部免疫介导的直接过敏反应的77%。由于CARPA临床普遍性,以及该反应与药物理化性质的相关性,补体活性检测被建议作为药物免疫毒性和药物一致性的评价指标之一。但是,由于补体活性的体内检测较为复杂、不同个体之间以及人与动物之间存在免疫差异,使得有必要建立一个标准、快捷的模型,用于评价药物对补体活性的影响。本研究使用人混合血清作为标准反应血清,通过加入热聚集Ig G和酵母多糖激活血清得到标准阳性对照,将SC5b-9、C5a、C4d和Bb作为检测指标并确定评价标准,建立了药物对补体活性影响的体外评价模型。应用该评价模型,以抗真菌类药物两性霉素B的不同处方和注射用伏立康唑为研究对象,对这些药物的免疫毒性以及仿制与市售制剂的一致性进行了初步评价。
[Abstract]:Complements activation-related pseudo-allergic reacts (CARPA) accounted for 77% of all immune-mediated direct allergic reactions. Because of the clinical universality of CARPA and the correlation between the reaction and the physicochemical properties of the drug, the detection of complement activity is suggested as one of the evaluation indexes of drug immunotoxicity and drug consistency. However, due to the complexity of in vivo detection of complement activity and the difference of immunity between individuals and animals, it is necessary to establish a standard and fast model to evaluate the effect of drugs on complement activity. In this study, the human mixed serum was used as the standard reactive serum, and the standard positive control was obtained by adding heat agglomeration IgG and yeast polysaccharide activated serum. The SC5b-9 C5aAX C4d and BB were used as the detection indexes and the evaluation criteria were determined. An in vitro evaluation model of the effect of drugs on complement activity was established. Using this evaluation model, the different prescriptions of amphotericin B and voleconazole for injection were used to evaluate the immunotoxicity of these drugs and the consistency between imitative and commercial preparations.
【作者单位】：石家庄市第五医院;石药集团中奇制药技术(石家庄)有限公司;河北中医学院;
【基金】：国家“十二五”重大新药创制资助项目(2014ZX09507001) 石家庄市科技支撑计划(151461193)
【分类号】：R96

【相似文献】