Page 31 - 2019年10月第30卷第19期

硫辛酸注射液仿制药与原研药的制剂质量比较及其小鼠急性毒

性实验研究 Δ

田 园 ，孔德志，刘紫琪，张赛航，任雷鸣（河北医科大学中西医结合学院，石家庄 050017）
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中图分类号 R965 文献标志码 A 文章编号 1001-0408（2019）19-2618-06
DOI 10.6039/j.issn.1001-0408.2019.19.06

摘 要 目的：对硫辛酸注射液的原研药与国内2个厂家的仿制药进行制剂质量比较及小鼠急性毒性实验研究，探讨一致性评价
方法的项目。方法：依据《中国药典》的相关质量标准，检测并比较3个厂家硫辛酸注射液样品的理化性质（性状、pH、渗透压等）、
含量、有关物质及小鼠急性毒性实验（n＝10）中的半数致死量（LD50 ）及以注射液原液注射给药后小鼠（n＝30）死亡情况。结果：原
研药与2个仿制药在理化性质和有关物质检查方面均符合质量标准，3个样品含量均为95％～105％；急性毒性试验结果显示2个
仿制药的 LD50 值（LD50：247.911 mg/kg，95％置信区间 222.209～277.999 mg/kg；LD50：215.291 mg/kg，95％置信区间 196.637～
235.053 mg/kg）明显低于原研药的 LD50值（LD50：266.534 mg/kg，95％置信区间 250.597～283.418 mg/kg），但差异无统计学意义
（P＞0.05）。取注射液原液直接单剂量注射时，3次重复实验结果显示2个仿制药引起的小鼠的死亡数（26、28只）与原研药（19只）
比较差异有统计学意义（P均＜0.05），且给药后原研药小鼠出现窜动和惊叫等兴奋性反应，而2个仿制药呈现抑制性反应。结论：
硫辛酸注射液的2个仿制药与原研药在制剂质量标准方面均符合《中国药典》的有关规定，但是急性毒性实验结果差异较大，难以
证明这2个仿制药与原研药的一致性；在注射液的一致性评价项目中建议纳入急性毒性实验。
关键词 一致性评价；硫辛酸注射液；含量；有关物质；理化性质；急性毒性实验

Comparison of the Quality of Generic and Original Preparations of Thioctic Acid Injection and Study on
Its Acute Toxicity Test in Mice
TIAN Yuan，KONG Dezhi，LIU Ziqi，ZHANG Saihang，REN Leiming（College of Chinese Integrative Medicine，
Hebei Medical University，Shijiazhuang 050017，China）

ABSTRACT OBJECTIVE：To compare the quality of original preparations of Thioctic acid injection and generic preparations
from 2 domestic manufacturers，discuss the acute toxicity test of mice and to investigate the project of consistency evaluation
methods. METHODS：According to the quality standard that stated in Chinese Pharmacopeia， physicochemical properties
（characters，pH，osmotic pressure，etc.，contents and related substances of samples of Thioctic acid injection as well as LD50 in
acute toxicity test （n＝10），and mortality of mice after administration of injection solution （n＝30） were compared among 3
manufacturers. RESULTS：The physicochemical properties as and related substances of the original drug and 2 generic drugs were
all in line with the quality standard；the contents of 3 samples ranged 95％-105％. The acute toxicity test results showed that the
LD50 values of 2 generic drugs（LD50：247.911 mg/kg，95％ confidence interval：222.209-277.999 mg/kg；LD50：215.291 mg/kg，
95％ confidence interval：196.637-235.053 mg/kg）were smaller than that of original drug（LD50：266.534 mg/kg，95％ confidence
interval：250.597-283.418 mg/kg），but there was no statistical difference（P＞0.05）. The results of 3 repeated experiments showed
that there was statistical significance in the number of animal death caused by the 2 generic drugs（26，28）was more than that of
the original drug（19）（all P＜0.05），when injection solution was injected into mice in a single dose. After administration of the
original drug，mice showed excitatory reactions such as movement and squeal，while 2 generic drugs showed inhibitory reactions.
CONCLUSIONS：2 generic drugs of Thioctic acid injection and the original drug all conform to the relevant regulations of Chinese
Pharmacopoeia in terms of preparation quality standards，but the results of acute toxicity test are quite different，so it is difficult to
prove the consistency between the 2 generic drugs and the original drug. Therefore，acute toxicity test is necessary for the
consistency evaluation of injections.
Δ 基金项目：河北省自然科学基金资助项目（No. H2016206030）
KEYWORDS Consistency evaluation； Thioctic acid
＊硕士研究生。研究方向：分子药理学。电话：0311-86266445。
E-mail：970557857@qq.com injection； Content； Related substances； Physicochemical
# 通信作者：教授。研究方向：分子药理学。电话：0311-86266722。 properties；Acute toxicity test
E-mail：ren-leiming@263.net

·2618 · China Pharmacy 2019 Vol. 30 No. 19 中国药房 2019年第30卷第19期