麻杏石甘汤胶体相态的拆分、表征及抗病毒研究  

Separation,characterization,and antiviral activity of colloidal phase state of Maxing Shigan Decoction

作　　者：李会竹 宋丹丹 常辰琦 路畅 刘悦 陈瑞[1] LI Hui-zhu;SONG Dan-dan;CHANG Chen-qi;LU Chang;LIU Yue;CHEN Rui(School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京中医药大学药学院,江苏南京210023

出　　处：《中国中药杂志》2023年第16期4394-4401,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82074125)。

摘　　要：该研究根据麻杏石甘汤中胶体颗粒尺寸不同对其进行分离、表征、含量测定及抗病毒药效研究。采用超滤法将麻杏石甘汤的混合胶体相态初步拆分为小胶体颗粒段(S)、中胶体颗粒段(M)、大胶体颗粒段(B),并用体积排阻色谱法进一步精细拆分,动态光散射法(DLS)及透射电镜法(TEM)表征分离后胶体颗粒的大小及形貌。UPLC-MS/MS测定不同胶体相态中麻黄碱、苦杏仁苷、甘草酸含量,EDTA络合滴定钙(Ca^(2+))含量。最后,滴鼻法建立呼吸道合胞病毒(RSV)感染小鼠模型,实验设空白组、模型组、利巴韦林组、麻杏石甘汤(MC)组、S组、M组、B组,灌胃给药治疗,考察小鼠肺组织病理变化及脏器指数。研究结果显示,麻黄碱、苦杏仁苷、甘草酸及Ca^(2+)含量在不同胶体段中分布并不均匀,其中B段是除Ca^(2+)外其他3种成分占比最高的部分,分别占全方的46.35%、53.72%、92.36%。体积排阻色谱法分离到粒径在100~500 nm的形貌均一的胶体颗粒。与S、M段相比,B段能提高RSV感染小鼠的肺指数抑制率(38.31%)、脾指数及胸腺指数,并改善小鼠肺组织炎症细胞浸润及肺损伤情况。麻杏石甘汤中的复杂成分通过加热形成大小不一、形态各异的胶体颗粒,麻黄碱、苦杏仁苷、甘草酸、Ca^(2+)等小分子活性成分都不同程度地参与组装。麻杏石甘汤中发挥抗病毒作用的主要物质基础就是加热过程中活性成分组装产生的具有一定粒径的胶体颗粒。This study focused on the separation,characterization,content determination,and antiviral efficacy research on colloidal particles with different sizes in Maxing Shigan Decoction(MXSG).The mixed colloidal phase of MXSG was initially separated into small colloidal particle segment(S),medium colloidal particle segment(M),and big colloidal particle segment(B)using ultrafiltration.Further fine separation was performed using size-exclusion chromatography.Dynamic light scattering(DLS)and transmission electron microscopy(TEM)were employed to characterize the size and morphology of the separated colloidal particles.UPLC-MS/MS was used to determine the content of ephedrine,amygdalin,glycyrrhizic acid,and the EDTA complexometric titration was used to measure the calcium(Ca^(2+))content in different colloidal phases.Finally,a respiratory syncytial virus(RSV)infection mouse model was established using intranasal administration.The experimental groups included a blank group,a model group,a ribavirin group,an MXSG group,an S group,an M group,and a B group.Oral administration was given for treatment,and pathological changes in mouse lung tissue and organ indices were evaluated.The results of the study showed that the distribution of ephedrine,amygdalin,glycyrrhizic acid,and Ca^(2+)content was not uniform among different colloidal segments.Among them,the B segment had the highest proportions of the three components,except for Ca^(2+),accounting for 46.35%,53.72%,and 92.36%,respectively.Size-exclusion chromatography separated colloidal particles with uniform morphology in the size range of 100-500 nm.Compared to the S and M segments,the B segment showed an increased lung index inhibition rate(38.31%),spleen index,and thymus index in RSV-infected mice,and it improved the infiltration of inflammatory cells and lung injury in the lung tissue of mice.The complex components in MXSG form colloidal particles of various sizes and morphologies through heating,and small-molecule active components such as ephedrine,amygdalin,glycyrrhizic ac

关 键 词：麻杏石甘汤 自组装 胶体颗粒 抗病毒 

分 类 号：R284.1[医药卫生—中药学] R285[医药卫生—中医学]