甲硝唑阴道用原位凝胶的急性毒性及阴道刺激性研究

目的研究甲硝唑阴道原位凝胶的急性毒性和阴道刺激性。方法采用改良寇氏法对小鼠进行全身急性毒性试验，用大鼠进行局部给药急性毒性试验，采用Eckstein法对性成熟雌性家兔进行阴道刺激性研究。结果小鼠腹腔注射甲硝唑原位凝胶的半数致死量（LD50）为（128．6±12．0）mg／kg；大鼠阴道给药无明显的全身和局部毒性反应；阴道刺激性试验中，家兔阴道刺激炎症总分值为5．11分，电镜下阴道上皮细胞完整，形态无明显变化。结论在试验剂量下，甲硝唑原位凝胶的LD50在中等毒性范围，阴道刺激性在可接受范围内，值得进一步研发。

Study on Acute Toxicity and Vaginal Irritation of Metronidazole In-Situ Vaginal Gels

Objective To evaluate the systemic and local acute toxicity and vaginal tolerance of Metronidazole In- Situ Vaginal Gels. Methods Modified Karber＇s method was used to test the lethal doses （LD50） in mice. The vaginal acute toxicity on SD rats was studied and vaginal irritation was observed on mature rabbits by Eckstein method. Results LD50 of the in- situ gels by intra- peritoneal injection was （128.6 ± 12.0）mg/kg in mice. The in-situ vaginal gels administered intravaginally had no significant systemic and local toxicity. The vaginal irritation score of the gels was 5. 11 in rabbits. The vaginal epithelia cells were integrated and had no significant morphological change. Conclusion In the experimental dose, LD50 of the in- situ gels belongs to moderate toxicity, the vaginal irritation is acceptable.