阴道用壬苯醇醚即型凝胶的制备与评价  

Preparation and Evaluation of Nonoxynol-9-loaded Thermoreversible Gel for Vaginal Application

作　　者：杨富金[1,2] 陈凌云[2] 俸灵林[3] 魏刚 陆伟跃 

机构地区：[1]教育部智能化递药重点实验室,复旦大学药学院药剂学教研室,上海201203 [2]云南中医学院,昆明650500 [3]上海市计划生育科学研究所,国家人口和计划生育委员会计划生育药具重点实验室,上海200032

出　　处：《中国药学杂志》2014年第22期2008-2013,共6页Chinese Pharmaceutical Journal

基　　金：国家科技支撑计划(2012BAI31B04)

摘　　要：目的制备以泊洛沙姆为基质的温度敏感型阴道用壬苯醇醚即型凝胶，并评价其流变学性能与体内滞留能力。方法利用倒置试管法测定胶凝温度，通过单因素实验考察泊洛沙姆与药物浓度对胶凝温度的影响。以相位角变化表征凝胶的相变过程，分别测试在模拟的储存、运输和使用状态下凝胶的流变学性质，并考察阴道模拟液稀释对凝胶相转变过程的影响。使用近红外荧光探针标记凝胶。小动物活体成像评价凝胶在小鼠体内的滞留能力。结果通过处方优化制得的凝胶其胶凝温度为（31．5±2）℃，相转变过程在3～4℃内完成，使用黏度（6．50Pa·s）〉储存黏度（1．023Pa·s）〉运输黏度（0．291Pa·s），且经阴道模拟液稀释后在体温条件下能形成凝胶。该凝胶在小鼠阴道内滞留时间长达4h。结论该凝胶的胶凝温度适宜，流变学性质良好，在阴道内滞留时间较长，满足阴道用药的要求。OBJECTIVE To develop a nonoxynol-9-1oaded thermorevesible gel for vaginal administration and evaluate its rheological properties and in vivo retention capacity. METHODS Gelation temperature was determined by tube inversion method. Effects of poloxamer and nonoxynol-9 concentrations on gelation temperature were studied by a single factor experiment. Rheological behavior of the gel was characterized using the temperature-dependent changes of phase angle. Viscosities were measured in the situation of simula- ted storage, transportation, and application, respectively. Effect of simulated vaginal fluid （VFS） on the gelating capability of the gel was also observed. The thermorevesible gel was then labeled by a near-infrared fluorescent probe, and the retention capacity was evalu- ated in mice＇s vagina using an in vivo fluorescence imaging technique. RESULTS The gelation temperature of the optimized gel was （31.5± 2） ℃. The gelation process was completed within a temperature change of 3 -4 ℃. The viscosities under different situations were in the order of application（6. 50 Pa · s） 〉 storage （1. 023 Pa· s） 〉 transportation （0. 291 Pa · s）. The formulation could still transform into a gel at body temperature after being diluted with VFS, and resided in mice＇s vagina for as long as 4 h. CONCLUSION The thermorevesible gel possesses suitable gelation temperature, rheological properties, and in vivo residence time, therefore has potential for vaginal application.

关 键 词：壬苯醇醚 泊洛沙姆 即型凝胶 流变学 小动物活体成像 

分 类 号：R944[医药卫生—药剂学]