Page 43 - 《中国药房》2022年10期

金丝桃苷混合纳米胶束的制备及其肠吸收研究 Δ

张宇航 ，邱智东，邱 野，王伟楠，刁元元，石羽文，姜孟成，刘伟朋，贾艾玲（长春中医药大学中药有效成分
＊
#
省部共建教育部重点实验室，长春 130117）

中图分类号 R943 文献标志码 A 文章编号 1001-0408（2022）10-1189-09
DOI 10.6039/j.issn.1001-0408.2022.10.07

摘 要 目的 制备金丝桃苷混合纳米胶束（Hyp-F127/TPGS）并优化其制备工艺，考察其肠吸收特性。方法 采用薄膜分散法制备
Hyp-F127/TPGS。在单因素实验和Plackett-Burman实验设计的基础上，结合Box-Behnken响应面法，以包封率和载药量为考察指
标，以F127-TPGS质量比、水化时间、Hyp投药量为因素，优化其制备工艺并验证；观察按最优工艺所制Hyp-F127/TPGS的外观、微
观形态并测定其粒径、多分散性指数（PDI）和Zeta电位；考察空白胶束（F127/TPGS）的临界胶束浓度（CMC）、Hyp-F127/TPGS的体
外释放行为和初步稳定性，利用大鼠在体单向肠灌流模型评价Hyp-F127/TPGS肠吸收特性。结果 Hyp-F127/TPGS的最优制备工
艺为：F127-TPGS 质量比 2 ∶ 1、水化时间 2 h、Hyp 投药量 9 mg；3 次验证实验结果显示，所制 Hyp-F127/TPGS 的包封率为（87.20±
0.99）％，载药量为（5.02±1.20）％，与预测值的偏差分别为0.92％和2.39％。按最优工艺所制胶束为黄色澄清透明溶液，具有良好
的丁达尔效应；透射电子显微镜下呈球形，形态完整且分布均匀，粒径为（15.02±0.16）nm，PDI 为 0.092±0.031，Zeta 电位为
（－6.67±1.47）mV；F127/TPGS的CMC为21 μg/mL，Hyp-F127/TPGS在4 ℃下存放4周的稳定性良好；Hyp-F127/TPGS和Hyp对
照品的累积释放率分别为（66.30±2.93）％（96 h）、（99.24±0.27）％（60 h）；Hyp-F127/TPGS和Hyp对照品在各肠段均有吸收，主要
吸收部位分别为空肠和十二指肠，前者的药物吸收速率常数和表观吸收系数均显著高于后者（P＜0.05或P＜0.01）。结论 优化所
得Hyp-F127/TPGS制备工艺稳定、可行；所制Hyp-F127/TPGS具有缓释效果，并在一定程度上促进了Hyp的肠吸收。
关键词 金丝桃苷；混合纳米胶束；制备工艺；肠吸收特性；Plackett-Burman设计；Box-Behnken响应面法；单向肠灌流模型

Study on the preparation of hyperoside mixed nanomicelles and its intestinal absorption
ZHANG Yuhang，QIU Zhidong，QIU Ye，WANG Weinan，DIAO Yuanyuan，SHI Yuwen，JIANG Mengcheng，
LIU Weipeng，JIA Ailing（Key Laboratory of Traditional Chinese Medicine Active Ingredient of Ministry of
Education，Changchun University of Chinese Medicine，Changchun 130117，China）

ABSTRACT OBJECTIVE To prepare hyperoside mixed nanomicelles （Hyp-F127/TPGS） and optimize its preparation
technology，and to investigate its intestinal absorption characteristics. METHODS Hyp-F127/TPGS was prepared by thin film
dispersion method. Based on single factor test and Plackett-Burman design，combined with Box-Behnken response surface method，
the preparation process was optimized and validated using entrapped efficiency（EE）and drug loading（DL）as evaluation indexes，
F127-TPGS mass ratio，hydration time and the amount of Hyp as factors. The appearance and microscopic morphology of
Hyp-F127/TPGS obtained by the optimal technology were observed，and the particle size，polydispersity index（PDI）and Zeta
potential were also determined. The critical micelle concentration（CMC）of blank micelle（F127/TPGS），in vitro release behavior
and preliminary stability of Hyp-F127/TPGS were investigated，and absorption characteristics of Hyp-F127/TPGS were investigated
by in situ unidirectional intestinal perfusion model. RESULTS The optimal preparation technology of Hyp-F127/TPGS included
F127-TPGS mass ratio of 2 ∶ 1，hydration time of 2 h，and Hyp amount of 9 mg. Results of three validation tests showed that the
EE of Hyp-F127/TPGS was（87.20±0.99）％，and the DL was（5.02±1.20）％，deviations from predicted values were 0.92％ and
2.39％. The micelles prepared by optimal technology were yellow，clear and transparent solution，with good Tyndall effect；under
transmission electron microscope，they were spherical，complete and evenly distributed；the particle size was（15.02±0.16）nm，
the PDI was 0.092±0.031，and the Zeta potential was（－6.67±1.47）mV. The CMC of F127/TPGS was 21 μg/mL，Hyp-F127/
TPGS was stable after 4 weeks of storage at 4 ℃，and the cumulative release rates of Hyp-F127/TPGS and Hyp control were
（66.30±2.93）％（96 h）and（99.24±0.27）％（60 h），respectively. Hyp-F127/TPGS and Hyp reference were absorbed in each
intestinal segment，and the main absorption sites were jejunum
Δ 基金项目：吉林省科技发展计划项目（No.20210204004YY，
and duodenum respectively；drug absorption rate constant and
No.20200602034ZP）；长春中医药大学“杏林学者工程”——青年科学
apparent absorption coefficient of the former were significantly
家项目（No.QNKXJ2-2021ZR26）
higher than those of the latter （P＜0.05 or P＜0.01）.
＊硕士研究生。研究方向：中药制剂新技术与新产品开发。
E-mail：zhangyuhangxz@163.com CONCLUSIONS The optimized preparation technology of
# 通信作者：硕士生导师，副教授。研究方向：中药制剂新技术与 Hyp-F127/TPGS is stable and feasible；prepared Hyp-F127/
新产品开发。E-mail：cczyyjal@163.com TPGS shows a sustained-release effect，which promotes the

中国药房 2022年第33卷第10期 China Pharmacy 2022 Vol. 33 No. 10 ·1189 ·