细辛脑注射制剂异常毒性检查标准研究

目的测定细辛脑注射制剂静脉给药的小鼠LD50值,同时起草本品异常毒性检查标准。方法采用加权回归机率单位法(Bliss法)对小鼠静脉给药测定LD50值,同时按照《中国药典》2010年版要求确定异常毒性检查限值,起草异常毒性标准。结果测定细辛脑注射制剂的小鼠LD50为51.9-153.1 mg/kg,为标准中拟增加异常毒性检查项,异常毒性检查项的限值建议定为15 mg/kg,按此限值检查结果符合规定。结论细辛脑注射制剂毒性较大,各企业生产工艺不同毒性也差异较大,为减少本品临床使用不良反应的发生,应在其质量标准中增加异常毒性检查项。

Study on Abnormal Toxicity Test Standard of Asarone Injection Preparation

Objective To measure the lethal dosage values (LD₅₀) of i.v. asarone injection for mice and to establish a standard for abnormal toxicity test of asarone injection to potentially reduce the occurrence of adverse drug reaction. Methods To obtain the LD₅₀ value, a weighted linear probit regression method (Bliss method) is employed. The limit of abnormal toxicity test is determined according to Appendix XI C in its 2010 edition of the Chinese pharmacopoeia. Results It is found that the LD₅₀ of intravenously asarone injection in mice ranges from 51.9 to 153.1 mg/kg. The abnormal toxicity test should be added as an additional item in the standard. Conclusions Based on analyses in this study, an appropriate limit of abnormal toxicity test is 15 mg/kg, which is also in line with current medical standard in China.