芍药苷及芍药苷磷脂复合物胶束在体肠吸收对比分析  

Comparative study of paeoniflorin and paeoniflorin phospholipid complex micelles in intestinal absorption

作　　者：袁腾腾 常红 唐亚楠 吕淑婕 方亮 王雷 陈卫东 张彩云 YUAN Tengteng;CHANG Hong;TANG Yanan;LYU Shujie;FANG Liang;WANG Lei;CHEN Weidong;ZHANG Caiyun(Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application,School of Pharmacy,Anhui University of Traditional Chinese Medicine,Hefei 230012,China;Engineering Technology Research Center of Modernized Pharmaceutics,Hefei 230012,China;Anhui Key Laboratory of Compound Chinese Materia Medica,Hefei 230012,China;Anhui Genuine Chinese Medicinal Materials Quality Improvement Innovation Collaborative Center,Hefei 230012,China)

机构地区：[1]安徽中医药大学药学院,药物制剂技术与应用安徽省重点实验室,安徽合肥230012 [2]安徽省教育厅现代药物制剂工程技术研究中心,安徽合肥230012 [3]中药复方安徽省重点实验室,安徽合肥230012 [4]安徽省道地中药材品质提升创新协同中心,安徽合肥230012

出　　处：《药学研究》2023年第8期562-566,573,共6页Journal of Pharmaceutical Research

基　　金：国家自然科学基金项目(No.51303006);安徽省教育厅基金项目(No.KJ2021ZD0065);安徽省重大专项(No.202203a07020031);省级大学生创新创业项目(No.S202110369017)。

摘　　要：目的比较芍药苷(PF)和芍药苷磷脂复合物(PF-PLC)胶束的肠吸收特点,探讨磷脂复合物胶束提高芍药苷生物利用度的作用机制。方法采用大鼠在体单向肠灌流模型,以吸收速率常数(K_(a))和有效渗透系数(P_(eff))为指标,通过超高效液相色谱(UPLC)测定不同浓度芍药苷原料药和芍药苷磷脂复合物胶束在十二指肠中的肠吸收情况。同时,在灌流液中添加维拉帕米,考察P-糖蛋白(P-gp)抑制剂对芍药苷原料药和芍药苷磷脂复合物胶束肠吸收的影响。结果芍药苷磷脂复合物胶束浓度的提高可显著增加芍药苷的肠道吸收(P<0.001,P<0.05)。在灌流液中加入维拉帕米后发现,与单纯芍药苷组比较,芍药苷+维拉帕米组的吸收速率常数和有效渗透系数值虽有增加的趋势,但无明显统计学差异;与芍药苷磷脂复合物胶束组比较,芍药苷磷脂复合物胶束+维拉帕米组差异也无统计学意义。结论大鼠在体单向肠灌流实验结果显示芍药苷磷脂复合物胶束的吸收主要是被动转运途径,且磷脂复合物胶束的形成显著改善了芍药苷在十二指肠的吸收。维拉帕米的加入对芍药苷磷脂复合物胶束的吸收无显著影响,即芍药苷磷脂复合物胶束的吸收不受外排转运体的影响,这可能是生物利用度提高的原因之一。Objective To compare the intestinal absorption characteristics of paeoniflorin(PF)and paeoniflorin phospholipid complex(PF-PLC)micelles,and to explore the mechanism of enhancing bioavailability of PF with nano-micelles.Methods The intestinal absorption characteristics of PF and PF-PLC micelles in duodenum at different concentrations were determined by ultra-high phase liquid chromatography(UPLC)with the absorption rate constant(K a)and effective permeability coefficient(P eff)as indexes.Meanwhile,verapamil was added into the perfusion solution to investigate the effect of P-glycoprotein(P-gp)inhibitor on intestinal absorption of PF and PF-PLC micelles.Results The increase of PF-PLC micelles concentration significantly increased intestinal absorption of PF(P<0.001,P<0.05).After adding verapamil into the irrigation fluid,K a and P eff values of PF+verapamil group showed an increasing trend,but no significant difference compared with PF group.Compared with the PF-PLC micelles group,there was no significant difference in PF-PLC micelles+verapamil group.Conclusion In vivo unidirectional intestinal perfusion experiment in rats showed that the absorption of PF-PLC micelles mainly existed passive transport pathway and the formation of phospholipid complex micelles significantly improved the absorption of PF in duodenum.The addition of verapamil had no significant effect on the absorption of PF-PLC micelles,that is,the absorption of PF-PLC micelles was not affected by efflux transporters,which may be one of the reasons for the improvement of bioavailability.

关 键 词：芍药苷 磷脂复合物 胶束 肠吸收 P-糖蛋白 在体单向肠灌流 

分 类 号：R285.5[医药卫生—中药学]