Page 53 - 《中国药房》2025年11期
P. 53

两种方法制备的水飞蓟宾纳米晶的在体肠吸收及组织分布研究
                                                                                                           Δ


                                                      #
          王梦颜 ，孙 莹，黄思睿，任娅博，常金花，刘喜纲（承德医学院中药研究所/河北省中药研究与开发重点实验室，
                ＊
          河北 承德 067000）

          中图分类号  R917；R944      文献标志码  A      文章编号  1001-0408（2025）11-1335-05
          DOI  10.6039/j.issn.1001-0408.2025.11.08

          摘  要  目的  研究两种方法制备的水飞蓟宾（Sy）纳米晶在大鼠各肠段的吸收特征和组织分布差异。方法  采用高压均质法和反
          溶剂沉淀法制备粒径相当的Sy纳米晶（即Sy-NS-G、Sy-NS-F）。将大鼠随机分为Sy原料药组、Sy-NS-G组和Sy-NS-F组，每组均
          设置低、中、高（60、120、180 μg/mL）3个质量浓度（以Sy计），每组3只；根据在体单向肠灌流实验，考察Sy原料药、Sy-NS-G和Sy-
          NS-F在大鼠不同肠段（十二指肠、空肠、回肠）的吸收速率常数（Ka ）和表观吸收系数（Papp ）。另将大鼠分为Sy原料药组、Sy-NS-G组
          和Sy-NS-F组，每组20只；各组大鼠单次灌胃剂量均为50 mg/kg（以Sy计），分别于给药后0.3、1、4、10、24 h处死，考察Sy原料药、
          Sy-NS-G和Sy-NS-F在心、肝、脾、肺、肾、脑和小肠的组织分布情况。结果  Sy-NS-G、Sy-NS-F、Sy原料药在十二指肠、空肠中的Ka、
          Papp随着Sy质量浓度的增加无明显变化（P＞0.05），Sy-NS-F在十二指肠的吸收高于Sy-NS-G，Sy-NS-G和Sy原料药的吸收部位主
          要在回肠，Sy-NS-F的吸收部位主要在十二指肠和回肠。Sy-NS-G和Sy-NS-F在大鼠不同组织中的分布不同，Sy-NS-G在大部分
          组织中1 h内达峰，分布浓度由高到低依次为小肠＞脾＞心＞肺＞肝≈脑＞肾；Sy-NS-F在大部分组织中也是1 h内达峰，分布浓
          度由高到低依次为小肠＞脾＞肾＞肺＞心≈肝＞脑。结论  Sy纳米晶在十二指肠、空肠中的吸收方式为被动扩散，且在十二指肠
          中，Sy-NS-F的吸收大于Sy-NS-G；Sy-NS-G和Sy-NS-F在大鼠体内的组织分布有明显区别。
          关键词  水飞蓟宾；纳米晶；在体单向肠灌流；组织分布；高压均质法；反溶剂沉淀法

          Study  on  the  in  vivo  intestinal  absorption  and  tissue  distribution  of  silybin  nanocrystals  prepared  by  two
          methods
          WANG Mengyan，SUN Ying，HUANG Sirui，REN Yabo，CHANG Jinhua，LIU Xigang（Institute  of  Chinese
          Materia  Medica，  Chengde  Medical  University/Hebei  Key  Laboratory  for  Research  and  Development  of  Chinese
          Medicine， Hebei Chengde 067000， China）

          ABSTRACT   OBJECTIVE  To  investigate  the  absorption  characteristics  and  tissue  distribution  of  silybin （Sy）  nanocrystals
          prepared  by  two  methods  in  different  intestinal  segments  of  rats.  METHODS  Sy  nanocrystals （i.e.  Sy-NS-G  and  Sy-NS-F）  with
          comparable  particle  sizes  were  prepared  using  high-pressure  homogenization  and  anti-solvent  precipitation  methods，  respectively.
          Rats  were  randomly  divided  into  three  groups：  Sy  raw  drug  group，  Sy-NS-G  group，  and  Sy-NS-F  group.  Each  group  was  further
          divided into three subgroups with low， medium， and high （60， 120， 180 μg/mL） mass concentrations （calculated based on Sy），
          with 3 rats in each subgroup. The absorption rate constant （Ka ） and apparent absorption coefficient （Papp ） of Sy raw drug， Sy-NS-G
          and  Sy-NS-F  in  different  intestinal  segments  were  investigated  by  using  the  in  vivo  one-way  intestinal  perfusion  experiment.
          Additionally，  the  rats  were  divided  into  three  groups:  Sy  raw  drug  group，  Sy-NS-G  group，  and  Sy-NS-F  group，  with  20  rats  in
          each  group.  Rats  in  each  group  were  administered  a  single  intragastric  dose  of  50  mg/kg （calculated  based  on  Sy）.  They  were
          sacrificed at 0.3， 1， 4， 10， and 24 hours post-administration respectively， to investigate the tissue distribution of Sy raw drug， Sy-
          NS-G， and Sy-NS-F in the heart， liver， spleen， lungs， kidneys， brain and intestines. RESULTS In duodenum and jejunum， the Ka
          and Papp of the nanocrystals prepared by the two methods remained unchanged with the increase of Sy concentration， and there was
          no significant difference （P＞0.05）； the absorption of Sy-NS-F in the duodenum was greater than that of Sy-NS-G； the absorption
          sites of Sy-NS-G and Sy raw drug were mainly in the ileum， while those of Sy-NS-F were mainly in the duodenum and ileum. The
          concentrations of Sy-NS-G and Sy-NS-F in different tissues of rats were different； Sy-NS-G peaked in most tissues at 1 h， and the
          distribution  concentration  was  as  follows：  intestine＞spleen＞heart＞lungs＞liver≈brain＞kidneys.  Sy-NS-F  reached  its  peak  at  1
          h，  and  the  distribution  concentration  was  in  the  order  of  intestine＞spleen＞kidney＞lung＞heart≈liver＞brain.  CONCLUSIONS
          The absorption mode of Sy nanocrystals in the duodenum and ileum is mainly passive diffusion. In the duodenum， the absorption of
                                                             Sy-NS-F  is  greater  than  that  of  Sy-NS-G；  there  are  significant
             Δ 基金项目 河北省自然科学基金项目（No.H2022406073）；河北
                                                             differences  in  the  tissue  distribution  of  Sy-NS-G  and  Sy-NS-F
          省中央引导地方科技发展资金项目（No.246Z2504G）；河北省高等学
                                                             in rats.
          校科学技术研究项目（No.ZD2022121）                            KEYWORDS     silybin；  nanocrystals；  unidirectional  intestinal
             ＊ 第一作者 硕 士 研 究 生 。 研 究 方 向 ：中 药 制 剂 。 E-mail：
                                                             perfusion   in   vivo；   tissue   distribution；   high-pressure
          1751731904@ qq.com
                                                             homogenization； anti-solvent precipitation method
             # 通信作者 教授，硕士生导师。研究方向：中药制剂。E-mail：
          liuxgmail@sina.com

          中国药房  2025年第36卷第11期                                              China Pharmacy  2025 Vol. 36  No. 11    · 1335 ·
   48   49   50   51   52   53   54   55   56   57   58