盐酸小檗碱缓释微球的制备及其治疗结肠炎的药效学研究  

Preparation of Berberine Hydrochloride Sustained Release Microspheres and Pharmacological Study on Its Treatment of Colitis

作　　者：汪洁 顾雪梅 唐铭烨 吕志阳 陈璟 陈静 WANG Jie;GU Xuemei;TANG Mingye;LYU Zhiyang;CHEN Jing;CHEN Jing(Hanlin College of Nanjing University of Chinese Medicine,Taizhou 225300,China)

机构地区：[1]南京中医药大学翰林学院,江苏泰州225300

出　　处：《山东化工》2024年第23期34-38,共5页Shandong Chemical Industry

基　　金：2024年江苏高校青蓝工程优秀教学团队资助项目;2023年江苏省大学生创新创业项目(202313981004Y,202313981011Y);泰州市科技支撑项目(TS202232,TS202325)。

摘　　要：目的:优化盐酸小檗碱缓释微球的制备工艺与处方,初步考察其对结肠炎小鼠的治疗作用。方法:采用乳化交联法制备盐酸小檗碱微球。通过BBD设计,以海藻酸钠溶液质量分数、氯化钙溶液质量分数和超声破碎时间为影响因素,包封率为评价指标,优化出最佳制备工艺及处方。并对微球的粒径和体外释放度进行测定。结肠炎小鼠连续灌胃盐酸小檗碱微球7 d,记录小鼠体质量变化和便血情况,ELISA法检测小鼠结肠TNF-α、IL-1β含量。结果:微球的最佳制备工艺处方为:海藻酸钠溶液质量分数为0.78%,氯化钙溶液质量分数为1.56%,超声破碎时间为10.17 min。最佳工艺处方的微球包封率均值为82.4%,平均粒径为0.64μm,体外释放结果表明,盐酸小檗碱微球制剂在24 h内累计释放率为95.3%,具有一定的缓释作用。药效学研究表明,盐酸小檗碱缓释微球能减缓小鼠体质量下降,改善便血情况,减少结肠组织中IL-1β和TNF-α的表达。结论:制备的盐酸小檗碱缓释微球具备一定的缓释性能,对结肠炎小鼠具有治疗作用。Objective:To optimize the preparation process and formula of berberine hydrochloride sustained release microspheres and preliminarily investigate their therapeutic effect on colitis in mice.Methods:Berberine hydrochloride microspheres were prepared by emulsion crosslinking method.By using Box-Behnken design,with sodium alginate concentration,calcium chloride concentration,and ultrasonic disruption time as influencing factors,and encapsulation rate as the evaluation index,the optimal preparation process and formula were optimized.The particle size and in vitro release rate of the microspheres were determined.Colitis mice were orally gavaged with berberine hydrochloride microspheres for 7 days,recording changes in body weight and rectal bleeding,observing colonic pathological changes by HE staining,and detecting the levels of TNF-α and IL-1β in colonic tissues of mice by ELISA.Results:The optimal process parameters and formula for the microspheres were as follows:sodium alginate concentration of 0.78%,calcium chloride concentration of 1.56%,and ultrasonic disruption time of 10.17 min.The average encapsulation rate of the optimal process formula was 82.4%,with an average particle size of 0.64μm.The in vitro release results showed that the cumulative release rate of hydrochloride berberine microspheres was 95.3% within 24 hours,indicating a certain sustained release effect.Pharmacological studies demonstrated that berberine hydrochloride sustained release microspheres could alleviate weight loss in mice,reduce colonic pathological damage,and decrease the expression of IL-1β and TNF-α in colonic tissues.Conclusion:The prepared berberine hydrochloride sustained release microspheres exhibited certain sustained release properties and therapeutic effects on colitis mice.

关 键 词：盐酸小檗碱 缓释微球 体外释放度 结肠炎 

分 类 号：TQ460.6[化学工程—制药化工] R944[医药卫生—药剂学]