摘要
为初步分析利福昔明(Rifaximin)在人工胃/肠液和肠道菌群及动物组织样品中的稳定性,将利福昔明分别与空白人工胃液(pH=1.3,不含酶)、空白人工肠液(pH=6.8,不含酶)、人工胃液(pH=1.3,含胃蛋白酶)、人工肠液(pH=6.8,含胰蛋白酶)、SD大鼠(雄性)肠道菌群及不同组织样品的匀浆液等共孵育不同时间后,采用高效液相色谱法(HPLC)检测剩余利福昔明百分比的变化。结果表明:1)在空白人工胃液中,随孵育时间的增加,剩余利福昔明百分比虽有下降,但仍在90%以上;在人工胃液中孵育6h,其剩余百分比为84.03%;而在空白人工肠液和人工肠液中孵育6h后,其剩余百分比则分别降至81.14%和78.12%。2)利福昔明在SD大鼠肠道菌群中孵育12h后,虽发生部分降解,但剩余百分比仍在90%以上,总体呈稳定的趋势。3)利福昔明在空白SD大鼠的胃、肝、小肠和大肠及内容物的匀浆液中分别孵育6h后,其剩余百分比分别为92.09%、75.95%、78.24%和83.90%。综上,利福昔明在酸性条件下较稳定,而在碱性条件下,胰蛋白酶、胃蛋白酶和肠壁、肝脏代谢酶等对其稳定性的影响亦较为有限。本研究将为兽用利福昔明口服制剂的开发提供数据支持。
To preliminarily analyze the stability of rifaximin in artificial gastric/intestinal fluid,the intestinal flora,and tissue samples of rat,rifaximin was spiked into blank artificial gastric fluid(pH=1.3,without enzyme),blank artificial intestinal fluid(pH=6.8,without enzyme),artificial gastric fluid(pH=1.3,with pepsin),artificial intestinal fluid(pH=6.8,with trypsin),the intestinal flora of SD rats(males)and homogenates of different tissue samples for different incubation time,respectively.The percentage of residual rifaximin was detected by high-performance liquid chromatography(HPLC).The results showed that:1)In blank simulated gastric fluid,the percentage of residual rifaximin decreased with the increase of incubation time,but it was still above 90%.After incubation in artificial gastric juice for 6h,the percentage of rifaximin was 84.03%.However,after incubation in the blank and artificial intestinal solutions for 6h,the percentages decreased to 81.14% and 78.12%,respectively.2)After incubation in the intestinal flora of SD rats for 12h,the percentage was still more than 90% with a stable trend although rifaximin exhibited partial degradation.3)When rifaximin was incubated in homogenates of rats’stomach,liver,small and large intestines for 6h,the percentages of residual rifaximin were 92.09%,75.95%,78.24% and 83.90%,respectively.In conclusion,rifaximin was more stable under acidic conditions while the stability could be influenced by alkaline conditions,pepsin,trypsin,intestinal wall and liver metabolic enzymes.The study will provide data support for the development of rifaxinmin oral preparations for animals.
作者
陶琦
刘希望
秦哲
白莉霞
李世宏
李剑勇
杨亚军
TAO Qi;LIU Xiwang;QIN Zhe;BAI Lixia;LI Shihong;LI Jianyong;YANG Yajun(Key Laboratory of New Animal Drug Project of Gansu Province/Key Laboratory of Veterinary Pharmaceutical Development ofMinistry of Agriculture and Rural Affairs/Lanzhou Institute of Husbandry and Pharmaceutical Sciences,Chinese Academy of Agricultural Sciences,Lanzhou 730050,China)
出处
《中国农业大学学报》
CAS
CSCD
北大核心
2022年第5期240-248,共9页
Journal of China Agricultural University
基金
中国农业科学院科技创新工程(25-LZIHPS-02)。
关键词
利福昔明
人工胃液
人工肠液
肠道菌群
组织样品
稳定性
rifaximin
artificial gastric fluid
artificial intestinal fluid
intestinal flora
tissue samples
stability
