盐酸青藤碱传递体的制备及其对大鼠类风湿性关节炎的药效评价  

Study on preparation of sinomenine hydrochloride transfersomes and their therapeutic effects on rheumatoid arthritis in rats

作　　者：魏燕[1] 张永生[1] 郑杭生[1] 费雅蓉 王娟[1] 诸佳珍[1] 兰济乐 

机构地区：[1]浙江中医药大学药学院,浙江杭州311402

出　　处：《中草药》2017年第23期4872-4879,共8页Chinese Traditional and Herbal Drugs

基　　金：浙江省医药卫生科技计划项目基金(2015111458);高等学校博士学科点专项科研基金(20123322120002);浙江省教育厅科研项目(Y201431480);浙江省自然科学基金项目(Y16H280006)

摘　　要：目的制备盐酸青藤碱传递体并对其处方工艺进行优化,验证其对大鼠类风湿性关节炎(RA)的治疗作用。方法采用乙醇注入法制备盐酸青藤碱传递体,以传递体的弹性为指标,通过正交试验优化其处方工艺;以恒定压力挤出法测定其弹性,HPLC法结合离心超滤法测定其包封率;于大鼠尾根部sc牛II型胶原建立Wistar大鼠RA模型,以大鼠踝关节评分、关节肿胀度、血清中肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的水平以及炎细胞浸润、血管翳形成、软骨破坏和骨侵蚀等组织病理形态学的变化来评价传递体对RA的治疗作用。结果盐酸青藤碱传递体最佳处方为蛋黄磷脂300 mg、胆固醇30 mg、盐酸青藤碱100 mg、脱氧胆酸钠60 mg、维生素E 5 mg、磷酸盐缓冲溶液(pH 8.0)23 mL、无水乙醇2 mL。以最佳处方制得的传递体的平均粒径为(83.31±0.08)nm,Zeta电位为(-32.57±3.27)mV,弹性指数为38.69±1.66,药物质量浓度为(2.96±0.27)mg/mL,包封率为(39.82±0.97)%。药效实验结果显示,盐酸青藤碱传递体可显著减轻由RA引起的关节肿胀(P<0.01),显著减少血清中TNF-α和IL-1β的水平(P<0.01),明显减轻炎症反应并有效改善踝关节部位的病理组织形态。结论所得的盐酸青藤碱传递体制备工艺可行,质量可控,疗效确切。Objective To optimize the formulation of sinomenine hydrochloride transfersomes（SHTs） and to verify their therapeutic effects on rheumatoid arthritis in rats.Methods SHTs were prepared by ethanol injection method.Their formulation was optimized by an orthogonal test,which was based on the elasticity of transfersomes.Elasticity of transfersomes was measured by constant pressure extrusion method and entrapment efficiency was measured by HPLC combined with centrifugation ultrafiltration.The model of rheumatoid arthritis was established by subcutaneous injection of type II collagen into Wistar rats＇ tail.The therapeutic effects of the preparation on rheumatoid arthritis in rats were evaluated based on ankle joint score,swelling degree,level of TNF-α and IL-1β in serum as well as histological changes including inflammatory cell infiltration,pannus formation,cartilage destruction,and bone erosion.Results The optimized formulation was as follows： egg phospholipid 300 mg,cholesterol 30 mg,sinomenine hydrochloride 100 mg,sodium deoxycholate 60 mg,vitamin E 5 mg,phosphate buffered saline（pH 8.0） 23 mL,and absolute ethyl alcohol 2 mL.The optimized transfersomes had an average size of（83.31 ± 0.08） nm,Zeta potential of（-32.57 ± 3.27） mV,deformability index of 38.69 ± 1.66,drug content of（2.96 ± 0.27） mg/m L,and entrapment efficiency of（39.82 ± 0.97） %.The results of pharmacodynamical test revealed that the preparation could significantly reduce joint swelling caused by rheumatoid arthritis（P〈0.01） and lower TNF-α and IL-1β level in serum（P〈0.01）,effectively alleviate inflammatory response and improve histological changes of ankle joint.Conclusion The preparation process for the transfersomes is feasible and their quality can be controlled.The optimized SHTs are effective for treatment of rheumatoid arthritis in rats.

关 键 词：盐酸青藤碱 传递体 乙醇注入法 弹性 类风湿性关节炎 药效评价 正交试验 包封率 

分 类 号：R283.6[医药卫生—中药学]