在体单向肠灌流模型测定甘草素的药物渗透性及生物药剂学分类预测  

Determination of drug permeability and biopharmaceutical classification of liquiritigenin in vivo by unidirectional intestinal perfusion model

作　　者：汪凯康 贾文 丁文华 刘群山 徐维平 WANG Kai-kang;JIA Wen;DING Wen-hua;LIU Qun-shan;XU Wei-ping(School of Pharmacy,Anhui University of Traditional Chinese Medicine,Hefei 230012;Department of Geriatrics,Gerontology Institute of Anhui Province,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001;Department of Pharmacy,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001)

机构地区：[1]安徽中医药大学药学院,合肥230012 [2]安徽省老年医学研究所,中国科学技术大学附属第一医院老年医学科(安徽省立医院),合肥230001 [3]中国科学技术大学附属第一医院药剂科(安徽省立医院),合肥230001

出　　处：《中南药学》2024年第2期302-306,共5页Central South Pharmacy

基　　金：国家自然科学基金项目(No.52072360)。

摘　　要：目的测定不同浓度甘草素在大鼠不同肠段的渗透性,初步探讨甘草素在肠道中的吸收机制,并对甘草素进行生物药剂学分类预测。方法参考2020年版《中国药典》中关于溶解度定义,考察甘草素在pH 1.2、4.0、6.8、7.4的缓冲液和水中的平衡溶解度来评价甘草素的溶解性,采用在体单向肠灌流模型测定甘草素在25、50、75μg·mL^(-1)对大鼠十二指肠、结肠、空肠、回肠的渗透性;结合溶解性和渗透性结果预测甘草素生物药剂学分类。结果甘草素在不同pH下和水中平衡溶解度都低于100μg·mL^(-1),溶解度为不溶或几乎不溶,亲脂性不强,甘草素在大鼠不同肠段下的渗透性都大于1.2×10^(-3)cm·min^(-1),为易吸收药物。结论甘草素在大鼠肠吸收中存在自身吸收抑制,存在吸收饱和特性,可能有主动转运或扩散等转运机制参与,预测甘草素为生物药剂学Ⅱ类药物,为低溶解度,高渗透性药物。Objective To determine the permeability of liquiritigenin at different concentrations,explore the absorption mechanism of liquiritigenin in different intestinal segments of rat,and predict the biopharmaceutical classification properties of liquiritigenin.Methods With reference to the definition of medium solubility in the 2020 Edition of Chinese Pharmacopoeia,the solubility of liquiritigenin was evaluated with the equilibrium solubility of buffer solution and water at pH 1.2,4.0,6.8,and 7.4.The permeability of liquiritigenin to duodenum,colon,jejunum and ileum of rats at 25,50,and 75μg·mL^(-1)was determined by in vivo unidirectional intestinal perfusion model.The biopharmaceutical classification of liquiritigenin was inferred by combining the solubility and permeability results.Results The equilibrium solubility of liquiritigenin was lower than 100μg·mL^(-1)at different pH values and in water,the solubility was low or almost insoluble,and lipophilicity was poor.The permeability of liquiritigenin in different intestinal segments of rats was greater than 1.2×10^(-3)cm·min^(-1),indicating easy absorption.Conclusion Liquiritigenin has self-absorption inhibition and saturation absorption characteristics in the intestinal of rats,which may involve the transport mechanism such as active transport or diffusion.Liquiritigenin is predicted to be a biopharmaceutical classⅡdrug with low solubility and high permeability.

关 键 词：甘草素 渗透性 肠灌流 生物药剂学分类 

分 类 号：R927.1[医药卫生—药学]