摘要
目的:探究三叶青地上部分抗炎提取物(THAA)固体纳米晶肠吸收动力学特性。方法:采用超高效液相色谱-质谱联用技术,CORTECS^(TM)UPLC-C_(18)色谱柱(100 mm×2.1 mm,1.6μm),乙腈(A)-水(含0.1%甲酸,5%甲醇)(B)梯度洗脱,建立同时测定大鼠在体肠灌流液中THAA固体纳米晶9个特征效应组分的定量分析方法。以大鼠在体单向肠灌流模型,考察比较THAA固体纳米晶、原料、普通颗粒剂中特征效应组分群在大鼠不同肠段的累积吸收量、最佳吸收部位及可能的转运机制。结果:大鼠在体肠灌流液中效应组分群的定量分析方法精密度及准确度良好,可用于肠吸收动力学研究;固体纳米晶保留了THAA效应组分群的肠吸收特性,十二指肠、回肠为最佳吸收部位;新绿原酸、绿原酸的肠吸收机制可能是促进扩散过程;异荭草苷-2’-O-鼠李糖苷、牡荆苷-2’-O-鼠李糖苷、异牡荆苷-2’-O-鼠李糖苷可能是被动吸收过程;荭草苷、异荭草苷、牡荆苷、异牡荆苷在高浓度时吸收可能存在饱和性抑制现象,存在被动吸收过程及主动转运和易化扩散。固体纳米晶组效应组分群在各肠段的表观吸收系数(P_(app))、吸收速率常数(K_(a))、累积吸收百分比(P_(%))均显著高于普通颗粒剂组及原料组(P均<0.05);肠吸收效率由高至低的顺序为THAA固体纳米晶、普通颗粒剂、原料。结论:固体纳米晶递药系统因粒子纳米化而显著提高了效应组分群在不同肠段及不同浓度水平条件下的肠吸收效率,适用于难溶性中药有效部位口服吸收的改善。
Objective:To investigate the characteristics of intestinal absorption kinetics of the anti-inflammatory extract(THAA)solid nanocrystals.Methods:Ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS/MS)combining CORTECS^(TM)UPLC-C_(18)column(100 mm×2.1 mm,1.6μm)and gradient elution of acetonitrile(A)-water(containing 0.1%formic acid,5%methanol)(B)was used to establishquantitative analysis method to simultaneously determine the main effect components of THAA solid nanocrystals in vivo intestinal perfusion fluid of rats.Using in vivo unidirectional intestinal perfusion model of rats,the cumulative absorption,optimal absorption site and possible transport mechanism of THAA solid nanocrystals,raw materials,and common granular effect components in different intestinal segments of rats were investigated and compared.Results:The established quantitative analysis method for the simultaneous determination of 9 effective components of THAA solid nanocrystals in rat intestinal perfusion fluid was precise and accuratet,and could be used for intestinal absorption kinetics research.THAA solid nanocrystals retained the THAA effect intestinal absorption characteristics of the components with duodenum and ileum as the best absorption sites.And the intestinal absorption mechanism of neochlorogenic acid and chlorogenic acid might promote the diffusion process.Isoorientin-2’-O-rhamnoside,vitexin-2’-O-rhamnoside,isovitexin-2’-O-rhamnoside might be a passive absorption process.At high concentrations,orientin,isoorientin,vitexin,isovitexin might be saturation inhibition.Their absorption mechanism was not only a passive absorption process,but also active transport and facilitated diffusion.In addition,the apparent absorption coefficient(P_(app)),drug absorption constant(K_(a)),and umulative absorption percentage(P_(%))values of the effect component group of the THAA solid nanocrystal group in the duodenum,ileum,jejunum,and colon were significantly higher than those of the ordinary granule group and the raw materi
作者
余文静
黄群
陈丹
廖淑彬
熊朝栋
YU Wen-jing;HUANG Qun;CHEN Dan;LIAO Shu-bin;XIONG Chao-dong(Department of Pharmacy,Fujian University of TCM,Fuzhou 350122,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2023年第2期262-279,共18页
Chinese Journal of Pharmaceutical Analysis
基金
福建省科技引导性项目(2019Y0037)
福建省中医药科技项目(2017FJZYZY202)
福建省科技计划项目(2010Y2004)。
关键词
三叶青地上部分抗炎提取物
固体纳米晶
效应组分群
在体单向肠灌流模型
肠吸收
anti-inflammatory extract from the aerial part of Tetrastigma hemsleyanum Diels et Gilg(THAA)
solid nanocrystals
effect component group
in vivo unidirectional intestinal perfusion model
intestinal absorption
