钩吻素子大鼠在体肠吸收动力学研究
|
摘要
目的:研究钩吻素子大鼠在体肠吸收动力学特征。方法:采用高效液相色谱法测定钩吻素子含量,以大鼠在体单向灌流法研究药物浓度、吸收部位和灌流液p H对钩吻素子肠吸收的影响。结果:小肠为钩吻素子主要吸收窗、十二指肠、空肠、回肠各段对钩吻素子的吸收无显著差异(P>0.05);钩吻素子吸收速率不受自身质量浓度影响,吸收机制符合被动扩散方式;钩吻素子在不同p H灌流液中吸收有显著性差异(P<0.05),碱性条件下钩吻素子吸收优于酸性条件。结论:钩吻素子在全肠段吸收良好,没有特定吸收窗口,提示该药物适合制成缓释制剂。
Objective: To investigate the intestinal absorption kinetics of koumine in rats. Methods: In situ single-pass perfusion method was used to study the effect of drug concentration,absorption site and p H of perfusion solution on the absorption of koumine. The concentration of koumine was determined by HPLC. Results:The absorption rates of koumine in duodenum,jejunum and ileum were not significantly different( P > 0. 05) and the intestinal absorption mechanism of koumine was passive diffusion. The concentration of koumine had no effect on its absorption,and the p H of perfusion solution had significant effect on it( P < 0. 05). Conclusion: Koumine is well adsorbed at all segments of intestine in rats where there is no special absorption site. Koumine is suitable to be developed as sustained-release preparation.
Objective: To investigate the intestinal absorption kinetics of koumine in rats. Methods: In situ single-pass perfusion method was used to study the effect of drug concentration,absorption site and p H of perfusion solution on the absorption of koumine. The concentration of koumine was determined by HPLC. Results:The absorption rates of koumine in duodenum,jejunum and ileum were not significantly different( P > 0. 05) and the intestinal absorption mechanism of koumine was passive diffusion. The concentration of koumine had no effect on its absorption,and the p H of perfusion solution had significant effect on it( P < 0. 05). Conclusion: Koumine is well adsorbed at all segments of intestine in rats where there is no special absorption site. Koumine is suitable to be developed as sustained-release preparation.
引文
[1]刘浩,俞昌喜.钩吻的研究进展[J].福建医科大学学报,2008,42(5):469-472.
[2]SU YP,SHEN J,XU Y,et al.Preparative separation of alkaloids from Gelsemium elegans Benth.using p H-zone-refining counter-current chromatography[J].J Chromatogr A,2011,1218(23):3695-3698.
[3]QIU HQ,XU Y,JIN GL,et al.Koumine enhances spinal cord3α-hydroxysteroid oxidoreductase expression and activity in a rat model of neuropathic pain[J].Mol Pain,2015,11:46-58.
[4]LING Q,LIU M,WU MX,et al.Anti-allodynic and neuroprotective effects of koumine,a Benth alkaloid in a rat model of diabetic neuropathy[J].Biol Pharm Bull,2014,37(5):858-864.
[5]XU Y,QIU H Q,LIU H,et al.Effects of koumine,an alkaloid of Gelsemium elegans Benth.,on inflammatory and neuropathic pain models and possible mechanism with allopregnanolone[J].Pharmacol Biochem Be,2012,101(3):504-514.
[6]俞昌喜,许盈,刘浩.作为唯一活性成份的钩吻素子在制备治疗慢性疼痛药物中的应用:中国,200810071467.X[P].2011-08-31.
[7]俞昌喜,许盈,杨渐,等.钩吻素子在制备治疗类风湿性关节炎药物中的应用:中国,201110174657.6[P].2012-08-29.
[8]LIU M,HUANG HH,YANG J,et al.The active alkaloids of Gelsemium elegans Benth.are potent anxiolytics[J].Psychopharmacology(Berl),2013,225(4):839-851.
[9]俞昌喜,刘铭,许盈,等.钩吻素甲、钩吻素子、1-甲氧基钩吻碱在制备治疗焦虑症药物中的应用:中国,201110130826.6[P].2013-03-27.
[10]许盈,郑宓,李苏平,等.钩吻素子在大鼠体内的药物代谢动力学及组织分布[J].福建医科大学学报,2013,47(4):199-203.
[11]潘德城,孙婷婷,孙勇兵,等.单向灌流法研究丹参提取物中丹参素和原儿茶醛大鼠肠吸收特性[J].中草药,2011,42(5):944-950.
[12]范景新,张文骥,颜廷旭,等.阿克他利大鼠在体肠吸收动力学[J].沈阳药科大学学报,2011,28(2):144-147.
[13]张燕,朱华旭,郭立玮.在体单向肠灌流模型研究小檗碱及其在复方配伍环境中的大鼠肠吸收特性[J].药学学报,2012,47(2):233-238.
[14]RAMA PY,MINAMIMOTO T,YOSHIKAWA Y.In situ intestinal absorption studies on low molecular weight heparin in rats using labrasol as absorption enhancer[J].Int J Pharm,2004,271(1-2):225-232.
[15]ABUASAL B,SYLVESTER PW,KADDOUMI A.Intestinal absorption of gamma-tocotrienol is mediated by Niemann-Pick C1-like 1:in situ rat intestinal perfusion studies[J].Drug Metab Dispos,2010,38(6):939-945.
[16]苏燕评,石冬梅,范振东,等.钩吻素子的基本理化性质与水溶液稳定性[J].福建医科大学学报,2013,47(4):195-198.
[17]FAGERHOLM U,JOHANSSON M,LENNERNAS H.Comparision between permeability coefficients in rat and human jejunum[J].Pharm Res,1996,13(9):1336-1342.
[2]SU YP,SHEN J,XU Y,et al.Preparative separation of alkaloids from Gelsemium elegans Benth.using p H-zone-refining counter-current chromatography[J].J Chromatogr A,2011,1218(23):3695-3698.
[3]QIU HQ,XU Y,JIN GL,et al.Koumine enhances spinal cord3α-hydroxysteroid oxidoreductase expression and activity in a rat model of neuropathic pain[J].Mol Pain,2015,11:46-58.
[4]LING Q,LIU M,WU MX,et al.Anti-allodynic and neuroprotective effects of koumine,a Benth alkaloid in a rat model of diabetic neuropathy[J].Biol Pharm Bull,2014,37(5):858-864.
[5]XU Y,QIU H Q,LIU H,et al.Effects of koumine,an alkaloid of Gelsemium elegans Benth.,on inflammatory and neuropathic pain models and possible mechanism with allopregnanolone[J].Pharmacol Biochem Be,2012,101(3):504-514.
[6]俞昌喜,许盈,刘浩.作为唯一活性成份的钩吻素子在制备治疗慢性疼痛药物中的应用:中国,200810071467.X[P].2011-08-31.
[7]俞昌喜,许盈,杨渐,等.钩吻素子在制备治疗类风湿性关节炎药物中的应用:中国,201110174657.6[P].2012-08-29.
[8]LIU M,HUANG HH,YANG J,et al.The active alkaloids of Gelsemium elegans Benth.are potent anxiolytics[J].Psychopharmacology(Berl),2013,225(4):839-851.
[9]俞昌喜,刘铭,许盈,等.钩吻素甲、钩吻素子、1-甲氧基钩吻碱在制备治疗焦虑症药物中的应用:中国,201110130826.6[P].2013-03-27.
[10]许盈,郑宓,李苏平,等.钩吻素子在大鼠体内的药物代谢动力学及组织分布[J].福建医科大学学报,2013,47(4):199-203.
[11]潘德城,孙婷婷,孙勇兵,等.单向灌流法研究丹参提取物中丹参素和原儿茶醛大鼠肠吸收特性[J].中草药,2011,42(5):944-950.
[12]范景新,张文骥,颜廷旭,等.阿克他利大鼠在体肠吸收动力学[J].沈阳药科大学学报,2011,28(2):144-147.
[13]张燕,朱华旭,郭立玮.在体单向肠灌流模型研究小檗碱及其在复方配伍环境中的大鼠肠吸收特性[J].药学学报,2012,47(2):233-238.
[14]RAMA PY,MINAMIMOTO T,YOSHIKAWA Y.In situ intestinal absorption studies on low molecular weight heparin in rats using labrasol as absorption enhancer[J].Int J Pharm,2004,271(1-2):225-232.
[15]ABUASAL B,SYLVESTER PW,KADDOUMI A.Intestinal absorption of gamma-tocotrienol is mediated by Niemann-Pick C1-like 1:in situ rat intestinal perfusion studies[J].Drug Metab Dispos,2010,38(6):939-945.
[16]苏燕评,石冬梅,范振东,等.钩吻素子的基本理化性质与水溶液稳定性[J].福建医科大学学报,2013,47(4):195-198.
[17]FAGERHOLM U,JOHANSSON M,LENNERNAS H.Comparision between permeability coefficients in rat and human jejunum[J].Pharm Res,1996,13(9):1336-1342.