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目的观察西藏小型猪宫颈外用鬼臼毒素(POD)纳米脂质载体(POD-NLC)后POD黏膜分布情况和系统毒性作用。方法应用随机数字表将西藏小型猪分为实验组和对照组,实验组宫颈涂0.5%POD-NLC,对照组涂0.5%POD酊剂。观察24 h不同时间宫颈黏膜刺激性、POD荧光强度及血中鬼臼毒素含量。结果实验组用药后未发现局部刺激,对照组出现红肿,水疱、血疱、糜烂、破溃等严重局部刺激反应;药物分布显示对照组在涂药4 h后黏膜组织中荧光值达到最高;实验组POD荧光值上升较慢,在16 h达最大值。实验组用药6 h后POD的血药浓度达峰值(14.28±0.33 ng/m L),对照组用药4 h后即达峰值(42.46±0.32 ng/m L),在所有测试时间点,实验组的血药浓度均低于对照组(P<0.05)。对照组的浓度曲线下面积是实验组的1.38倍。结论 POD-NLC具有缓释性、在黏膜较长时间蓄积,动物实验显示无局部刺激性且系统吸收低。
Objective To observe the distribution of POD mucosa and the systemic toxicity of POD-NLC after oral administration of small pigs in Tibet. Methods Tibetan miniature pigs were divided into experimental group and control group by random number table. The experimental group received 0.5% POD-NLC cervical smear and 0.5% POD tincture in the control group. Cervical mucosal irritation, POD fluorescence intensity and podophyllotoxin content in blood were observed at 24 h. Results In the control group, no local irritation was found. The control group showed severe local irritation such as redness, blisters, blood blisters, erosion and rupture. The drug distribution showed that the fluorescence value of the control group reached the highest after 4 h of application. Group POD fluorescence increased slowly, reaching the maximum at 16 h. After 6 h of treatment, the peak plasma POD concentration was 14.28 ± 0.33 ng / m L in the experimental group and 42.46 ± 0.32 ng / m L after 4 h in the control group. At all test time points, the experimental group The plasma concentration of the two groups were lower than that of the control group (P <0.05). The area under the concentration curve of the control group was 1.38 times of the experimental group. Conclusions POD-NLC has sustained release and accumulates in the mucosa for a long time. Animal experiments show no local irritation and low systemic absorption.