利福昔明子宫注入剂稳定性及其对家兔阴道黏膜刺激性研究

为研究利福昔明子宫注入剂的稳定性，从而初步确定其保质期，本试验取3批利福昔明子宫注入剂进行稳定性试验考察，包括影响因素、高温加速及长期稳定性，利用高效液相色谱法测定试验过程中利福昔明含量及有关物质的含量，从而初步确定利福昔明子宫注入剂的保质期。根据相关技术指导原则对家兔进行阴道刺激性试验。稳定性试验结果表明，根据面积归一化法计算有关物质的含量均不超过3%，注入剂的性状、沉降、粒度未发生明显变化，主成分利福昔明的含量变化在拟定标示量90.0%~110.0%范围内，从而确定本品的有效期为2年。家兔阴道刺激性试验结果显示，利福昔明子宫注入剂给药部位（阴道）和生理盐水对照组给药部位都没有出现红斑和水肿，刺激强度的评分为0；试验组和对照组的阴道黏膜没有出现明显的充血、水肿及异常分泌物流出的现象，阴道黏膜刺激指数为0.25。因此，利福昔明子宫注入剂对家兔的阴道无刺激性。本品的临床安全性良好，可进一步推广使用。

Study on the Stability of Rifaximin Uterine Infection and Its Stimulation to Vaginal Mucosa in Rabbits

In order to study the stability of the rifaximin uterine injection,and initially determined its quality guarantee period,three batches of rifaximin were used to test the stability of uterine injectors,including the influencing factors test,the high temperature accelerated test and long term stability test,the content of rifaximin and its related substances were determined by high performance liquid chromatography (HPLC).Thus,the quality guarantee period of rifaximin uterine injection was preliminarily determined.Referring to the relevant technical specifications,rabbit vaginal mucous membrane irritation test was studied.The results showed that the contents of the related substances were not more than 3% according to the area normalization method,the properties,sedimentation and particle size of the injector did not change significantly,and the change of the content of rifaximin in the principal component was 90.0% to 110.0%,the validity of this product was determined to be two years.In rabbit vaginal mucous membrane irritation test,the results showed that erythema and edema were not been found on rifaximin uterus implants administration site skin and saline control site skin,and the score was 0 point.In the vaginal mucous membrane irritation test,leukocyte infiltration,hyperemia and edema were not found in vaginal mucosa of test and control groups,vaginal mucous membrane irritation index was 0.25.So,rifaximin uterus injection had no irritation on rabbit vaginal mucous membrane.This product had good clinical safety and could be further promoted and used.