治糜康栓商品中重金属、有害元素分析及其毒理学研究

Analysis of heavy metals,harmful elements and toxicological research in Zhimikang suppository

目的:分析治糜康栓商品中重金属及有害元素,并研究其最大耐受量、阴道急性毒性、阴道黏膜刺激性,评价治糜康栓临床应用的安全性。方法:应用ICP-OES/MS技术对治糜康栓商品中重金属等元素进行分析;通过SD大鼠阴道急性毒性试验、新西兰兔阴道黏膜刺激性试验对治糜康栓的毒理作用进行研究。结果:治糜康栓商品中重金属及有害元素Cu、As、Cd、Hg、Pb的平均含量分别为0. 397,0. 077,0. 002,0. 019,0. 140 mg·kg-1。阴道急性毒性试验中,大鼠一日内对正品治糜康栓和伪品治糜康栓的最大耐受量为成人每日用量的112倍,在观察期内大鼠的一般状况、体质量及大体解剖均未发现异常。阴道黏膜刺激性试验中,正品治糜康栓和伪品治糜康栓以0. 16 g·kg-1的剂量连续7 d经兔阴道给药后,2组动物的阴道黏膜刺激性评分均小于8分。结论:治糜康栓商品中重金属及有害元素的含量均低于《中国药典》2015年版及化妆品规定的限量值;实验剂量下正品治糜康栓和伪品治糜康栓的阴道黏膜刺激性均在临床可接受范围内。

OBJECTIVE To analyze the heavy metals and harmful elements in Zhimikang suppository,and to study the maximum tolerance,acute vaginal toxicity and vaginal irritation test to evaluate the safety in clinical application.METHODS The contents of heavy metals and other inorganic elements in Zhimikang suppository were determined by means of ICP-OES/MS,then acute toxicity test and vaginal mucosal irritation test were performed to study the toxicology.RESULTS The average contents of heavy metals and harmful elements Cu,As,Cd,Hg and Pb in Zhimikang suppository were 0.397,0.077,0.002,0.019 and 0.140 mg·kg-1.In the acute toxicity test,the maximum tolerable dose of the rats for authentic and fake Zhimikang suppository was 112 times of the daily dose of human.During the observation period,the general condition,weight and general anatomy of the rats showed no abnormality.In the vaginal mucosal irritation test,both authentic and fake Zhimikang suppositories were administered at a dose of 0.16 g·kg-1 one time a day for 7 d consecutively.The results showed that the irritation score of the vagina mucosa of authentic and fake Zhimikang suppositories was less than 8 points.CONCLUSION The contents of heavy metals and harmful elements in Zhimikang suppository are below the limited value of Chinese Pharmacopoeia of the 2015 edition and cosmetics standards.The vaginal mucosal irritations of authentic and fake Zhimikang suppositories at the experimental dose are both acceptable in clinical practice.