盐酸小檗碱经海藻酸/大豆蛋白复合微球负载后的释放行为

盐酸小檗碱经海藻酸/大豆蛋白复合微球负载后的释放行为 Release Behavior of Berberine Encapsulated by Complex Microsphere Based on Alginate and Soy Protein Isolate 许沛虎 XU Peihu1 1 2 3 4 first-author 郭锋蜂 GUO Fengfeng1 1 2 3 4 黄进 HUANG Jin1 1 2 3 4 张双硕 ZHANG Shuangshuo1 1 2 3 4 熊富良 XIONG Fuliang1 1 2 3 4 武汉理工大学化学工程学院/湖北省中药制剂工程研究中心 武汉理工大学化学工程学院/湖北省中药制剂工程研究中心 School of Chemical Engineering,Wuhan University of Technology/Hubei Provincial Pharmaceutical Research Center of Traditional Chinese Medicine School of Chemical Engineering,Wuhan University of Technology/Hubei Provincial Pharmaceutical Research Center of Traditional Chinese Medicine 武汉理工大学化学工程学院/湖北省中药制剂工程研究中心,湖北,武汉,430070 武汉理工大学化学工程学院/湖北省中药制剂工程研究中心,湖北,武汉,430070 Key Laboratory of Cellulose and Lignocellulosics Chemistry of Guangzhou Institute of Chemistry,Chinese Academy of Sciences Key Laboratory of Cellulose and Lignocellulosics Chemistry of Guangzhou Institute of Chemistry,Chinese Academy of Sciences 中国科学院广州化学研究所纤维素化学重点实验室 中国科学院广州化学研究所纤维素化学重点实验室 ,广东,广州,510650 ,广东,广州,510650 利用海藻酸（AL）/大豆蛋白（SPI）复合微球包裹盐酸小檗碱（Ber）,研究了盐酸小檗碱经复合微球负载后在模拟胃,小肠和结肠pH环境下的释放行为.结果显示,在模拟肠和结肠的pH 6.8和pH 7.4环境中,约5 h盐酸小檗碱就分别达到96%和99%的药物溶出量,而在模拟胃的pH 1.0条件下溶出量仅为约40%.研究发现盐酸小檗碱经复合微球负载后的释放行为与复合微球在不同pH条件下的溶胀行为直接相关,即在pH 1.0时溶胀度很小,但在pH 6.8和pH 7.4条件下溶胀度可达到约2000%.这主要归功于海藻酸组分的pH敏感性.同时,负载过程使结晶的疏水盐酸小檗碱转变为更易于在水性介质中扩散和溶解的不定型态.特别是通过pH梯度实验发现,限定载药复合微球在模拟胃的pH 1.0溶液中的时间在3 h内,可控制盐酸小檗碱的溶出量为约20%;而在此后的小肠和结肠的pH条件下,盐酸小檗碱迅速溶出,使累积溶出量达到98%.由此可见,利用自主研制的复合微球负载盐酸小檗碱可以降低盐酸小檗碱对胃部的刺激并可应用于盐酸小檗碱对溃疡性结肠炎的治疗,同时大豆分离蛋白的生理活性可望发挥一定的辅助作用. The Berberine was encapsulated in a complex microsphere based on alginate（AL） and soy protein isolate（SPI）,and then the release behavior was investigated.The results showed that the release content reached 96% and 99%,respectively,under the pH conditions of intestine（pH 6.8） and colon（pH 7.4） in 5 hours while the release content under the stomach pH（pH 1.0） was only about 40%.It was well consistent with the swelling behavior of complex microsphere under various pH,i.e.the swelling ratio was about 2 000% under pH 6.8 and pH 7.4 and very small under pH 1.0.It was attributed to the pH sensitivity of AL component.Meanwhile,the encapsulation induced the transformation from crystalline to amorphous state for berberine,which facilated to the dissolution and diffusion of hydrophobic drugs in aqueous media.Especially,the results of drug release under pH-gradient suggested that the release content of berberine in complex microsphere could be limited as 20% under pH 1.0（the pH in stomach） in 3 hours,and then rapidly increased up to 98% under the pH conditions of intestne and colon.As a result,the encapsulation of berberine by complex microsphere can hindered the irritation of drug to stomach,and is suitable to the therapy of ulcerous colonitis.In addition,the bioactivity of SPI component is expected to play an assistant role. 盐酸小檗碱 药物释放 海藻酸 大豆分离蛋白 微球 berberine drug release alginate soy protein isolate microsphere R94 湖北省自然科学基金资助项目（2007ABA252） 2008-02-01 2021-04-01 2