摘要
该研究从药动学、药效学及组织分布的角度考察制备的口服共载葛根素(PUE)/大豆苷元(DAZ)混合胶束(PUE/DAZ-FS/PMMs)的递药性能。以PUE混悬液、单一载药胶束(PUE-FS/PMMs)、共载胶束(PUE/DAZ-FS/PMMs)为研究对象,考察大鼠血浆中PUE的血药浓度变化情况;采用大鼠尾容积测压法连续10周监测给药后自发性高血压大鼠(SHR)的收缩压、舒张压及平均血压变化;采用LC-MS/MS测定心、肝、脾、肺、肾、脑、睾丸中PUE的含量。结果表明,相较于PUE混悬液和PUE-FS/PMMs,PUE/DAZ-FS/PMMs在大鼠体内的C_(max)显著增加(P<0.01),相对生物利用度达122%,其C_(max)、AUC_(0-t)、AUC_(0-∞)、t_(1/2)、MRT分别是PUE混悬液的1.77、1.22、1.22、1.17、1.13倍,是PUE-FS/PMMs的1.76、1.16、1.08、0.84、0.78倍;与模型对照组相比,PUE/DAZ-FS/PMMs降低SHR大鼠的收缩压、舒张压和平均血压均有显著效果(P<0.05),其降血压程度均大于PUE混悬液,且高剂量下PUE/DAZ-FS/PMMs降血压效果强于PUE-FS/PMMs;此外,PMMs组在各组织中分布呈现剂量依赖,且PMMs组在代谢相关组织肾及肝中的分布低于混悬液组,而在大脑中的分布高于常规剂量组。可推测,PUE/DAZ-FS/PMMs不仅能更好地改善PUE的生物利用度,有效协同发挥药效,且胶束可一定程度延缓药物的消除,并促进药物穿透血脑屏障,为同源成分共载混合胶束的开发奠定基础。
In this study,the drug delivery performance of the prepared oral co-loaded puerarin/daidzein mixed micelles(PUE/DAZ-FS/PMMs)was investigated from the perspectives of pharmacokinetics,pharmacodynamics and tissue distribution.With PUE suspension,single drug-loaded micelle(PUE-FS/PMMs)and co-loaded micelle(PUE/DAZ-FS/PMMs)as the research objects,the changes of plasma concentration of PUE in rats were first investigated.The changes of systolic blood pressure,diastolic blood pressure and mean blood pressure in spontaneously hypertensive rats(SHR)after administration were monitored by tail volume manometry for ten consecutive weeks;The content of PUE in heart,liver,spleen,lung,kidney,brain and testis was determined by LC-MS/MS.The results showed that the C_(max)of PUE/DAZ-FS/PMMs in rats was significantly increased(P<0.01)and the relative bioavailability reached 122%compared with PUE suspension and PUE-FS/PMMs.TheC_(max)、AUC_(0-t)、AUC_(0-∞)、t_(1/2)、MRT,and MRT of PUE/DAZ-FS/PMMs were 1.77,1.22,1.22,1.17,and 1.13 times higher than those of PUE suspension,and 1.76,1.16,1.08,0.84,and 0.78 times higher than those of PUE-FS/PMMs,respectively.Compared with the model control group,PUE/DAZ-FS/PMMs had significant effects on reducing systolic blood pressure,diastolic blood pressure and mean blood pressure of SHR rats(P<0.05),and the degree of blood pressure reduction was greater than that of PUE suspension,and the effect of PUE/DAZ-FS/PMMs was stronger than that of PUE-FS/PMMs at high doses;In addition,the distribution of PMMs group in various tissues was dose dependent,an d the distribution of PMMs group in the metabolism-related tissues kidney and liver was lower than that in the suspension group,while the distribution in the brain was higher than that in the conventional dose group.It can be speculated that PUE/DAZ-FS/PMMs can not only better improve the bioavailability of PUE,effectively exert synergistic effects,but also delay the elimination of drugs to a certain extent and promote the penetration of drugs through the blood-brain barrier,laying a foundation for the development of homologous components co-loading mixed micelles.
作者
吴文婷
郭子璐
戈淑超
况文亮
李文栋
王上点
刘鹏
周志炜
朱卫丰
WU Wen-ting;GUO Zi-lu;GE Shu-chao;KUANG Wen-liang;LI Wen-dong;WANG Shang-dian;LIU Peng;ZHOU Zhi-wei;ZHU Wei-feng(School of Modern Chinese Medicine and Pharmaceutical Industry,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;Key Laboratory of Modern Preparation Chinese Materia Medica of Ministry of Education,Jiangxi University of Chinese Medicine,Nanc hang 330004,China;School of Pharmacy,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Pharmaceutical Technology,Hangzhou 310052,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2023年第18期5068-5077,共10页
China Journal of Chinese Materia Medica
基金
江西省教育厅科学技术研究项目(GJJ211232)
江西省自然科学基金青年项目(20212BAB216013)
江西中医药大学重点学科青年教师培养计划项目(2021jzzdxk004)
江西中医药大学校级科技创新团队项目(CTXD22006)。
关键词
葛根素
大豆苷元
聚合物混合胶束
药动学
药效学
组织分布
puerarin
daidzein
polymer mixed micelles
pharmacokinetics
pharmacodynamics
tissue distribution
