药学学报, 2013, 48(12): 1836-1843
引用本文:
关志宇, 张丽华, 陈丽华, 朱卫丰, 刘红宁. 贝母提取物中贝母甲素和贝母乙素的大鼠肠吸收特性[J]. 药学学报, 2013, 48(12): 1836-1843.
GUAN Zhi-yu, ZHANG Li-hua, CHEN Li-hua, ZHU Wei-feng, LIU Hong-ning. Rat intestinal absorption trait of peimine and peiminine in Thunberg Fritillary Bulb extract[J]. Acta Pharmaceutica Sinica, 2013, 48(12): 1836-1843.

贝母提取物中贝母甲素和贝母乙素的大鼠肠吸收特性
关志宇, 张丽华, 陈丽华, 朱卫丰, 刘红宁
江西中医药大学, 江西 南昌 330004
摘要:
本文考察了浙贝母醇提浸膏中贝母甲素和贝母乙素的肠吸收特征以及配伍影响。建立了HPLC-ELSD测定肠灌流液中贝母甲素和贝母乙素含量测定的方法,并进行了方法学研究。采用大鼠在体单向灌流法,重量法校正实验结果,分别考察灌流速度、灌流液pH、性别差异、胆总管结扎、药物浓度、不同肠段、维拉帕米和配伍苦杏仁、甘草对贝母甲素、乙素肠吸收的影响。结果表明:灌流速度、灌流液pH和浓度可影响贝母甲素和贝母乙素吸收,pH 6.8和pH 7.4时吸收有显著差异(P<0.01);灌流液中药物浓度升高,贝母甲素和贝母乙素的肠吸收参数呈下降趋势,低浓度和中、高浓度间吸收速度常数(Ka)和表观渗透系数(Papp)有显著性差异(P<0.01);贝母甲素和贝母乙素在雌鼠肠道中的吸收显著低于雄鼠(P<0.01);胆管结扎可显著影响贝母甲素和贝母乙素的吸收(P<0.05),贝母甲素和贝母乙素在各个肠段均有一定吸收,且无显著性差异(P > 0.05);加入维拉帕米对浸膏中贝母甲素和贝母乙素的吸收无显著性影响(P > 0.05);苦杏仁和甘草与贝母在常用配伍剂量下皆能显著降低贝母甲素和贝母乙素的肠吸收(P<0.01),药材单煎后组合与合煎两组间二者吸收无显著性差异(P > 0.05)。实验结果说明,贝母甲素和贝母乙素的体内吸收特征基本一致,二者在整个肠道均有一定吸收,并具有显著的性别差异,吸收机制可能有主动吸收或易化扩散参与;配伍苦杏仁、甘草可降低其肠吸收速度。
关键词:    贝母甲素      贝母乙素      小肠吸收      单向灌流法      重量法     
Rat intestinal absorption trait of peimine and peiminine in Thunberg Fritillary Bulb extract
GUAN Zhi-yu, ZHANG Li-hua, CHEN Li-hua, ZHU Wei-feng, LIU Hong-ning
Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
Abstract:
To study the in situ intestinal absorption kinetics and compatibility influence of peimine and peiminine in rats, the absorption of peimine and peiminine in small intestine (duodenum, jejunum and ileum) and colon of rats was investigated using in situ single-pass perfusion method and the drug content was measured by HPLC-ELSD. Perfusion rate, pH, concentration of drug, gender and bile duct ligation can significantly affect the absorption of peimine and peiminine, the Ka and Papp values in the condition of pH 6.8 and pH 7.4 had significant difference (P<0.01), as drug concentration increased, the absorption parameters of peimine and peiminine decreased, Ka and Papp between low concentrations and middle concentrations was significant difference (P<0.01). Verapamil can not affect Ka and Papp of peimine and peiminine which are in the extract (P > 0.05). Bitter almonds and licorice can significantly reduce the absorption of peimine and peiminine with the usual dose (P<0.01), extracted separately and together had no significant difference on Ka and Papp (P > 0.05). Experimental results show that the absorption features of peimine and peiminine are basically the same, both of them could be absorbed at all segments of the intestine in rats and had no special absorption window, and with significant differences between male and female individuals. The absorption of peimine and peiminine complies with the active transport and facilitated diffusion in the general intestinal segments. Bitter almond and licorice can reduce the intestinal absorption rate of peimine and peiminine.
Key words:    peimine    peiminine    intestinal absorption    single-pass intestinal perfusion    gravimetric method   
收稿日期: 2013-06-23
基金项目: 国家自然科学基金资助项目(81060346).
通讯作者: 陈丽华
Email: chlly98@163.com
相关功能
PDF(391KB) Free
打印本文
0
作者相关文章
关志宇  在本刊中的所有文章
张丽华  在本刊中的所有文章
陈丽华  在本刊中的所有文章
朱卫丰  在本刊中的所有文章
刘红宁  在本刊中的所有文章

参考文献:
[1] Zhang MF, Shen YQ, Zhu ZP, et al. Study of Chinese herbs property about pungent, warm and channel tropism of the Pi and Wi (4) analgesic effect[J]. Pharmacol Clin Chin Mater Clin Med (中药药理与临床), 1996, 11: 1-4.
[2] Zhang MF, Shen YQ. Advances in the pharmacological research on Fritillaria[J]. Shanghai Med Pharm J (上海医药), 2007, 10: 459-461.
[3] Chen KK, Chen L A, Chow TQ. The pharmacological action of peimine and peiminine[J]. J Am Pharm Assoc, 1933, 22: 638-641.
[4] Qian BC, Xu HJ. Studies on the antitussive and sedative activities of peimine and peiminine[J]. Acta Pharm Sin (药学学报), 1985, 20: 306-308.
[5] Wang S, Xu XP, Li T. Determination and contrastion of alkaloids and saponins in bulbus fritillariae cirrhosae and in other beimus[J]. Chin J Chin Mater Med (中国中药杂志), 2002, 27: 342-344.
[6] Jiang Y, Li P. Determination of verticine and verticinone in Bulbus Fritillariae Thunbergii by HPLC-ELSD[J]. Chin Pharm J (中国药学杂志), 2005, 40: 1257-1259.
[7] Liu LL, Chen LH, Zhu WF, et al. Pharmacokinetics of peimine in rabbits[J]. Chin J Pharm (中国医药工业杂志), 2011, 42: 914-916.
[8] Chen LH, Liu LL, Liu HN, et al. Simultaneous determination of peimine and peiminine in rat plasma by LC-MS/MS and its application in the pharmacokinetic study[J]. Acta Pharm Sin (药学学报), 2010, 45: 891-894.
[9] Chen LH, Zhang HM, Guan ZY, et al. Sex dependent pharmacokinetics, tissue distribution and excretion of peimine and peiminine in rats assessed by liquid chromatography-tandem mass spectrometry[J]. J Ethnopharmacol, 2013, 145: 77-84.
[10] Peng JJ, Lin CC, Li J, et al. Intestinal absorption kinetics of flurbiprofen in rats[J]. Acta Pharm Sin (药学学报), 2013, 48: 423-427.
[11] Yang XW. Principle and Control of Experimental Error (实验误差原理与控制)[M]. Beijing: Science Press, 2009: 62.
[12] Du D, Di LQ, Shan JJ, et al. Intestinal absorption of daphnetin by rats single pass perfusion in situ[J]. Acta Pharm Sin (药学学报), 2009, 44: 922-926.
[13] Guan ZY, Pu CH, Zhao KJ. Study on preparation of β-cyclodextrin inclusion compound for borneolum syntheticum from huoxuezhitong capsules[J]. Chin Med Mat (中药材), 2006, 29: 66-71.
[14] Xu L, Yang ZL. Intestinal absorption properties of hesperidin by single pass perfusion model on rats[J]. Chin Pharm J (中国药学杂志), 2009, 44: 594-597.
[15] Kan D, Ge L, Yee PH, et al. Prederivatization and high-performance liquid chromatographic analysis of alkaloids of bulbs of Fritillaria[J]. J Pharm Sci, 1996, 85: 1174-1179.
[16] Wu XD, Chen JJ, Pan YJ. Simultaneous determination of peimine and peiminine in rat plasma by LC-ESI-MS employing solid-phase extraction[J]. Biomed Chromatogr, 2010, 24: 902-907.
[17] Xin GZ, Zhou JL, Qi LW, et al. Turbulent-flow chromatography coupled on-line to fast high-performance liquid chromatography and mass spectrometry for simultaneous determination of verticine, verticinone and isoverticine in rat plasma[J]. J Chromatogr B, 2010, 878: 435-441.
[18] Lennernäs H, Lee ID, Fagerholm U, et al. A residence time distribution analysis of the hydrodynamics within the intestine in man during a regional sing le-pass perfusion with Loc-I-Gut: in vivo permeability estimation[J]. J Pharm Pharmacol, 1997, 49: 682-686.
[19] Curran PF, Solomon AK. Ion and water fluxes in the ileum of rats[J]. J Gen Physiol, 1957, 41: 143-168.
[20] Fagerholm U, Johansson M, Lennernäs H. Comparison between permeability coefficients in rat and human jejunum[J]. Pharm Res, 1996, 13: 1336-1342.
[21] Kobayashi S, Tanabe S, Sugiyama M, et al. Transepithelial transport of hesperetin and hesperidin in intestinal Caco-2 cell monolayers[J]. Biochim Biophys Acta, 2008, 1778: 33-41.
[22] Molpeceres J, Chacón M, Berges L, et al. Age and sex dependent pharmacokinetics of cyclosporine in the rat after a single intravenous dose[J]. Int J Pharm, 1998, 174: 9-18.