郑京玉,李国峰,何忠梅,祝洪艳,赵岩,郜玉钢,杨鹤,张连学
ZHENG Jing-yu,LI Guo-feng,HE Zhong-mei,ZHU Hong-yan,ZHAO Yan,GAO Yu-gang,YANG He,ZHANG Lian-xue

• 1:吉林农业大学中药材学院
• 2:吉林省人参工程技术创新中心
• 3:长春中医药大学附属医院

摘要(Abstract)：

该文通过灌胃和尾静脉2种方式对大鼠给予黄藤总生物碱,采用RP-HPLC测定大鼠血浆中巴马汀与药根碱的浓度变化后,通过3P97软件计算巴马汀与药根碱的药代动力学参数和口服生物利用度。大鼠经灌胃与尾静脉2种方式给予黄藤总生物碱60 mg·kg~(-1)后,测得的主要药代动力学参数如下:灌胃给药组中巴马汀和药根碱的Cmax分别为(0.91±0.06),(0.70±0.08)mg·L~(-1),tmax分别为(35.24±0.83),(47.76±1.24)min,t1/2分别为(187.03±1.53),(105.64±16.99)min,AUC分别为(280.30±18.69),(144.36±1.06)mg·min·L~(-1);静脉注射给药组中巴马汀和药根碱的t1/2分别为(172.18±12.38),(147.26±1.82)min,AUC分别为(2 553.14±214.91),(328.83±10.81)mg·min·L~(-1)。巴马汀的口服生物利用度为10.98%,药根碱的口服生物利用度为43.90%。
In this study,the total alkaloids of Huangteng were given to the rats by the methods of intragastric administration and tail vein. After the concentration changes of palmatine and jatrorrhizine in the plasma of rats were determined by RP-HPLC,pharmacokinetic parameters and oral bioavailability were calculated by 3P97 software. After the rats were pre-treated with total alkaloid 60 mg·kg~(-1)by the methods of intragastric administration and tail vein,the main pharmacokinetic parameters were determined as follows: in the intragastric administration group,the Cmaxof palmatine and jatrorrhizine were( 0. 91 ± 0. 06),( 0. 70 ± 0. 08) mg·L~(-1); tmaxof palmatine and jatrorrhizine were( 35. 24 ± 0. 83),( 47. 76 ± 1. 24) min; t1/2 of palmatine and jatrorrhizine were( 187. 03 ± 1. 53),( 105. 64 ± 16. 99) min,AUC of palmatine and jatrorrhizine were( 280. 30 ± 18. 69),( 144. 36 ± 1. 06) mg·min·L~(-1); in the intravenous injection group,the t1/2of palmatine and jatrorrhizine were( 172. 18 ± 12. 38),( 147. 26 ± 1. 82) min; AUC of palmatine and jatrorrhizine were( 2 553. 14 ± 214. 91),( 328. 83 ± 10. 81) mg·min·L~(-1). The oral bioavailability of palmatine was 10. 98% and jatrorrhizine was 43. 90%.

关键词(KeyWords)： 黄藤总生物碱;巴马汀;药根碱;药代动力学;口服生物利用度;RP-HPLC
total alkaloids of Huangteng;palmatine;jatrorrhizine;pharmacokinetics;oral bioavailability;RP-HPLC

Abstract:

Keywords:

基金项目(Foundation): 吉林省中医药产业发展专项(20140311029YY);; 吉林省教育厅“双十”培育项目(201442)

作者(Author): 郑京玉,李国峰,何忠梅,祝洪艳,赵岩,郜玉钢,杨鹤,张连学
ZHENG Jing-yu,LI Guo-feng,HE Zhong-mei,ZHU Hong-yan,ZHAO Yan,GAO Yu-gang,YANG He,ZHANG Lian-xue

参考文献(References)：

• [1]吕娜,赵昱玮,汲立伟,等.黄藤的研究进展[J].中国实验方剂学杂志,2016,22(19):199.
• [2]中国药典.一部[S].2015.
• [3]Rao G X,Zhang S,Wang H M,et al.Antifungal alkaloids from the fresh rattan stem of Fibraurea recisa Pierre[J].J Ethnop Harmacol,2009,123(1):1.
• [4]杨勇,叶小利,李学刚.四种黄连生物碱的抑菌作用[J].时珍国医国药,2007,18(12):3013.
• [5]Zhou X,Lin X,Xiong Y,et al.Chondroprotective effects of palmatine on osteoarthritis in vivo and in vitro:a possible mechanism of inhibiting the Wnt/β-catenin and hedgehog signaling pathways[J].Int Immunopharmacol,2016,34:129.
• [6]蒋秀燕,王丛丛.MECC-AD法测定黄连和黄柏中小檗碱、巴马汀和药根碱的含量[J].山东化工,2014,43(4):84.
• [7]Wu J,Xiao Q,Zhang N,et al.Photodynamic action of palmatine hydrochloride on colon adenocarcinoma HT-29 cells[J].Photodiagn Photodyn,2016,15:53.
• [8]Dhingra D,Bhankher A.Behavioral and biochemical evidences for antidepressant-like activity of palmatine in mice subjected to chronic unpredictable mild stress[J].Pharmacol Rep Pr,2014,66(66):1.
• [9]周敏,杨秀兰,成中太.紫外分光光度法测定黄藤素注射液中盐酸巴马汀含量的探索[J].合成化学,2001(4):379.
• [10]张慧,王义明,谢媛媛,等.HPLC法同时测定黄藤素注射液中黄藤素和盐酸药根碱的含量[J].中国药房,2012,23(7):625.
• [11]Liao C,Chang S,Yin S,et al.A HPLC-MS/MS method for the simultaneous quantitation of six alkaloids of Rhizoma corydalis Decumbentis in rat plasma and its application to a pharmacokinetic study[J].J Chromatogr B Anal Technol Biomed Life Sci,2014,944(4):101.
• [12]张慧,余琛,洪有采,等.HPLC-FLU法测定血清中黄藤素的含量[J].药学学报,2000,35(7):518.
• [13]田开鑫,肖丹,彭衡阳,等.LC-MS/MS测定大鼠血浆中黄藤素含量及其药代动力学研究[J].中国医药生物技术,2012,20(7):120.
• [14]Ma H D,Wang Y J,Guo T,et al.Simulataneous determination of tetrahydropalamatin,protopine,and palmatinee in rat plasma by LC-ESI-MS and its application to a pharmacokinetic study[J].J Pham Biomed Anal,2008,49(2):440.
• [15]Xu B,Li P,Zhang G.Comparative pharmacokinetics of puerarin,daidzin,baicalin,glycyrrhizic acid,liquiritin,berberine,palmatine and jateorhizine by liquid chromatography-mass spectrometry after oral administration of Gegenqinlian decoction and active components alignment[J].J Chromatogr B Anal Technol Biomed Life Sci,2015,988C:33.
• [16]Liu Q F,Shi X J,Li Z D,et al.Pharmacokinetic comparisons of berberine and palmatine in normal and metabolic syndrome rats[J].J Ethnopharmacol,2014,151(1):287.
• [17]Chen Y,Li Y,Wang Y,et al.Comparative pharmacokinetics of active alkaloids after oral administration of Rhizoma Coptidis extract and Wuji Wan formulas in rat using a UPLC-MS/MS method[J].Eur J Drug Metab Pharm,2015,40(1):67.
• [18]涂星,唐洪梅,柴玉娜,等.反相高效液相色谱法测定肠激安胶囊中芍药苷、盐酸小檗碱和盐酸巴马汀含量[J].药物分析杂志,2015(1):115.
• [19]Ding X,Tang Y,Sun A,et al.Simultaneous determination of three alkaloids in Huangbo using an ionic liquid as a mobile phase additive in reversed-phase liquid chromatography[J].J Sep Sci,2014,38(3):374.
• [20]Peng C C,Wang S P,Jin H Z,et al.Bioanalysis and pharmacokinetics of eight active components from Huanglian Jiedu decoction in rat plasma by LC-ESI-MS/MS method[J].Chin Herbal Med,2014,6(3):198.
• [21]梁瑞峰,张峰,时丽菲,等.UPLC-MS/MS法研究小檗碱、巴马汀和药根碱在大鼠体内的组织分布[J].药物分析杂志,2016(8):1421.
• [22]全红娜,金松子,雷勇胜,等.反相高效液相色谱中流动相选择与优化的研究进展[J].现代药物与临床,2014,29(10):1190.
• [23]黄娟萍,罗裕,江力,等.中药药动学研究中给药剂量的现状分析[J].中国药学杂志,2012,47(21):1685.