金丝桃苷磷脂复合物及其介孔二氧化硅纳米粒的制备和口服药动学研究  

Preparation of hyperoside phospholipids complex and its mesoporous silica nanoparticles and oral pharmacokinetics study

作　　者：李伟宏 郑伟 王风云 隋海娟 LI Wei-hong;ZHENG Wei;WANG Feng-yun;SUI Hai-juan(Henan Vocational College of Applied Technology,Zhengzhou 450042,China;Jinzhou Medical University,Jinzhou 121001,China)

机构地区：[1]河南应用技术职业学院,河南郑州450042 [2]锦州医科大学,辽宁锦州121001

出　　处：《中草药》2023年第13期4157-4167,共11页Chinese Traditional and Herbal Drugs

基　　金：河南省高等学校重点科研项目计划(23B320013);妇科肿瘤科研创新团队(2021-TD-02);河南应用技术职业学院骨干教师(2020-GGJS-Y008)。

摘　　要：目的制备金丝桃苷磷脂复合物(hyperosidephospholipidscomplex,Hyp-PC)介孔二氧化硅纳米粒(Hyp-PC mesoporous silica nanoparticles,Hyp-PC-MSN),考察口服药动学行为。方法以复合率为指标,单因素实验结合Box-Behnken设计-效应面法优化Hyp-PC处方。X射线粉末衍射(X-ray powder diffraction,XRPD)对Hyp-PC进行晶型分析,并测定Hyp-PC的油水分配系数。溶剂挥发法制备Hyp-PC-MSN,扫描电子显微镜观察Hyp-PC-MSN微观形态,并与Hyp-PC比较Hyp-PC-MSN体外溶出情况。SD大鼠分为金丝桃苷组、Hyp-PC组和Hyp-PC-MSN组,测定大鼠血浆中金丝桃苷质量浓度,计算Hyp-PC和Hyp-PC-MSN主要药动学参数及相对口服吸收生物利用度。结果Hyp-PC最佳处方的复合率接近100%,金丝桃苷在Hyp-PC中以无定型状态存在,油水分配系数明显增大。Hyp-PC-MSN外观形态呈球形,包封率为(93.17±0.85)%,载药量为(7.54±0.33)%,粒径为(163.87±6.15)nm,PDI值为0.108±0.009,ζ电位为(-0.28±0.05)m V。Hyp-PC-MSN明显提高了释药速率和累积释放度。药动学结果显示,Hyp-PC-MSN的达峰时间(tmax)显著性提前,半衰期(t1/2)延长至(4.56±0.82)h,达峰浓度(Cmax)提高至(1462.62±163.94)ng/mL,相对口服生物利用度提高至3.47倍。结论Hyp-PC-MSN可提高金丝桃苷体外溶出速率、累积溶出度及口服吸收生物利用度。Objective To prepare hyperoside phospholipids complex(Hyp-PC)mesoporous silica nanoparticles(Hyp-PC-MSN),and study oral pharmacokinetics behavior.Methods Taking the recombination rate as index,single factor experiment combined with Box-Behnken design-response surface methodology to optimize the formulation of Hyp-PC.Crystalline form of Hyp-PC was analyzed by X-ray powder diffraction(XRPD).Oil-water partition coefficient of Hyp-PC was determined.Solvent evaporation was used to prepare Hyp-PC-MSN.Microscopic appearance of Hyp-PC-MSN was observed by scanning electron microscope(SEM),and its dissolution in vitro was compared to Hyp-PC.SD rats were divided into hyperoside suspension group,Hyp-PC group and Hyp-PC-MSN group,hyperoside concentration in plasma was determined,and main pharmacokinetic parameters and relative oral bioavailability of Hyp-PC and Hyp-PC-MSN were calculated.Results Recombination rate of optimized formulations of Hyp-PC was close to 100%.Hyperoside was an amorphous substance in Hyp-PC and the oil-water partition coefficient was enhanced greatly.Microscopic appearance of Hyp-PC-MSN was spherical in shape.Average envelopment efficiency was(93.17±0.85)%,drug loading was(7.54±0.33)%,particle size was(163.87±6.15)nm,PDI value was 0.108±0.009 and ζ potential was(-0.28±0.05)mV.Drug release rate and cumulative release rate in vitro was greatly promoted.Pharmacokinetics results showed that tmax of Hyp-PC-MSN was advanced significantly,t1/2 was prolonged to(4.56±0.82)h,Cmax was increased to(1462.62±163.94)ng/mL and oral bioavailability was enhanced to 3.47 times.Conclusion Hyp-PC-MSN could increase dissolution rate,cumulative dissolution rate in vitro and the oral bioavailability of hyperoside.

关 键 词：金丝桃苷 磷脂复合物 油水分配系数 介孔二氧化硅纳米粒 溶出速率 累积溶出度 生物利用度 

分 类 号：R283.6[医药卫生—中药学]