科博肽注射液异常毒性及过敏反应方法学研究

Methodology Study on the Abnormal Toxicity Test and Sensitization Test of Cobratide Injection

目的:重新建立科博肽注射液“异常毒性”和“过敏试验”检查项限值,为其安全用药提供参考。方法:通过试验计算本品LD50,LD1及其可信限,确定其异常毒性检查法的限值。测定本品豚鼠腹腔和静脉给药的无毒反应剂量,采用豚鼠过敏试验的方法设定腹腔致敏和静脉过敏激发的剂量限值。结果:原有质量标准中,异常毒性检查项的限值修改为“取本品,加氯化钠注射液制成每1 mL中含科博肽2μg的溶液”,过敏反应检查项的限值修改为2μg/mL,致敏每只用0.5 mL,激发每只用1 m L。结论:为减少临床不良反应和确保质量标准的可行性,科博肽注射液的异常毒性和过敏试验检查限值设定为2μg/mL和2μg/mL。

Objective:To re-establish detection limits for“abnormal toxicity test”and“sensitization test”of Cobratide Injection,and provide reference for its safe use.Methods:Through the LD50,LD1 value and their confidence limits,determine the limit of abnormal toxicity test.By determining the non-toxic reaction doses after intraperitoneal(ip)and intravenous(iv)administration for guinea pigs to figure out the limits for sensitization ip and challenge iv of guinea pig sensitization test.Results:In the original quality standard,the limit of abnormal toxicity test was changed to“the product was prepared with sodium chloride injection into a solution containing 2μg of Cobratide in 1 mL”.The sensitization test limit was changed to 2μg/mL,0.5 mL for sensitization dose,1.0 mL for challenge dose.Conclusion:In order to reduce the clinical ADR and feasibility of ensuring quality standard,the limits of abnormal toxicity and sensitization test for cobratide injection were set at 2μg/mL and 2μg/mL.