摘要
目的:探讨经典名方四逆汤(SNT)煎煮过程中所形成自沉淀的主要机制,为探索SNT复方配伍毒效成分差异变化提供研究基础。方法:测定SNT合煎液、甘草-附子合煎液(GF)、附子-干姜合煎液(FJ)、甘草-干姜合煎液(GJ)、附子单煎液(FZ)、干姜单煎液(GJ)、甘草单煎液(GC)自沉淀的平均沉淀得率。对SNT自沉淀、GF自沉淀、FZ自沉淀、GC自沉淀4种主要自沉淀样品的粒径、pH、溶解性总固体(TDS)及电导率等物理参数进行表征,以及扫描电镜(SEM)微观观察,傅里叶变换红外光谱(FT-IR)分析。对SNT、SNT自沉淀、SNT上清液采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱法(UPLC-QExactive Orbitrap-MS)鉴定SNT复方合煎液及不同相态的化学成分,结合高效液相色谱法(HPLC)测定其主要毒效成分的含量。结果:SNT合煎与单煎自沉淀7种样品的沉淀得率结果显示,SNT自沉淀得率最高,SNT自沉淀的形成主要与附子和甘草成分反应生成复合物有关,FT-IR说明甘草对自沉淀形成的影响最大;通过UPLC-Q-Exactive-MS/MS鉴定出SNT合煎液中共有110种成分,包含SNT自沉淀中100种成分和SNT上清液中106种成分;主要毒效成分的定量结果表明,附子和甘草成分反应生成复合物,使游离的甘草苷、苯甲酰新乌头原碱、苯甲酰乌头原碱、苯甲酰次乌头原碱、甘草素、乌头碱、次乌头碱、异甘草素、甘草酸铵等成分的含量大小为SNT合煎液>上清液>自沉淀。结论:SNT在复方合煎过程中发生自沉淀现象,其中甘草对其形成的影响最大,提示甘草在SNT配伍减毒中发挥了较大作用。SNT复方合煎自沉淀毒效成分差异变化主要表现在成分含量变化上,体现SNT“体外沉积、体内缓释”的特点及SNT在临床上应用中强调“顿服”的重要性。
Objective:To explore the main mechanism of self-precipitation formed during the decoction of Sinitang(SNT),and to provide a research basis for exploring the differences in the toxic and effective components of this compound.Methods:The average precipitation yields of SNT,Glycyrrhizae Radix et Rhizoma(GRR)-Aconiti Lateralis Radix Praeparata(ALRP)decoction(GF),ALRP-Zingiberis Rhizoma(ZR)decoction(FJ),GRR-ZR decoction(GJD),ALRP decoction(FZ),ZR decoction(GJ)and GRR decoction(GC)were determined.The four main self-precipitation samples of SNT,GF,FZ and GC were physically characterized by particle size,scanning electron microscopy(SEM),pH,total dissolved solids(TDS),conductivity,and Fourier transform infrared spectroscopy(FT-IR)analysis.The chemical compositions of SNT decoction and its different phases was identified by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS)for SNT,SNT self-precipitation and SNT supernatant,and the contents of its main toxic and effective components were determined by high performance liquid chromatography(HPLC).Results:Precipitation yield results of the 7 samples of SNT decoction and single decoction showed that SNT had the highest self-precipitation yield.The formation of SNT self-precipitation was mainly related to the reaction between ALRP and GRR components to form complexes,and FT-IR showed that GRR had the greatest influence on the formation of self-precipitation.A total of 110 components were identified in the SNT decoction,including 100 components in the SNT self-precipitation and 106 components in the SNT supernatant.And quantitative results of the main toxic and effective components revealed that the reaction between ALRP and GRR components formed complexes,resulting in the following content hierarchy for free components:SNT decoction>supernatant>selfprecipitation,these components included free liquiritin,benzoylmesaconine,benzoylaconitine,benzoylhypacoitine,liquiritigenin,aconitine,hypoaconitine,isoliquiritigenin and ammonium glycyrrhizinate.Conclusion:SNT exhibits spontaneous precipitation during compound decoction,with GRR exerting the greatest influence on its formation.This suggests GRR plays a significant role in the detoxification of SNT.The differences in the self-precipitated toxic-effective components of SNT compound decoction primarily manifest as changes in component content,reflecting the characteristics of SNT"deposition in vitro and sustained release in vivo"and the importance of"administered at draught"in the clinical application of SNT.
作者
李美慧
冯熙
罗欣雨
周珏翰
黄运亚
李舒涵
成颜芬
傅舒
LI Meihui;FENG Xi;LUO Xinyu;ZHOU Juehan;HUANG Yunya;LI Shuhan;CHENG Yanfen;FU Shu(State Key Laboratory of Southwest Chinese Medicine Resources,School of Pharmacy,Chengdu University of Traditional Chinese Medicine(TCM),Chengdu 611137,China;Hospital of Chengdu University of TCM,Chengdu 610041,China;College of Food and Biological Engineering,Chengdu University,Chengdu 610106,China)
出处
《中国实验方剂学杂志》
北大核心
2025年第22期145-152,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
四川省自然科学基金项目(2023NSFSC0688)。
关键词
四逆汤
自沉淀
物理表征
毒效成分
经典名方
不同相态
形成机制
Sinitang
self-precipitation
physical characterization
toxic and effective components
famous classical formulas
different phases
formation mechanisms
