张博,刘晓娜,周越,胡丽萍
ZHANG Bo1,LIU Xiao-na2,ZHOU Yue1,HU Li-ping1(1.School of Pharmacy

• 1:辽宁中医药大学药学院
• 2:吉林大学药学院

摘要(Abstract)：

目的研究苏合香中主要成分肉桂酸在苏合香不同配伍和剂型在SD大鼠体内的药代动力学。方法 Sprague-Dawley(SD)大鼠分别口服苏合香(styrax)、二香活心软胶囊(erxianghuoxin softcapsules,简称ER)和二香亚微乳剂(erxiang submicron emulsion,简称EM),采用UPLC-MS/MS色谱法测定大鼠血浆中肉桂酸的浓度。用DAS2.0药动学软件处理血药浓度数据。用SPSS统计软件对所得的药动学数据进行显著性差异分析。结果大鼠口服Styrax、ER、EM三种制剂后,Styrax和ER中肉桂酸的药-时曲线符合单室模型,EM中肉桂酸的药-时曲线符合双室模型。口服Styrax和ER后,肉桂酸的药动学参数AUC0-t、AUC0-∞、ρmax、tmax、V无显著性差异(P>0.05),而口服EM后,ρmax、tmax显著性增加,V显著性减小(P<0.05),其他药动学参数无明显差异。结果表明降香油和苏合香合用后,苏合香中肉桂酸的药代动力学参数无显著性变化;制备成亚微乳剂后,提高了肉桂酸的血药浓度,减小了表观分布容积。结论降香油对苏合香主要成分肉桂酸的口服吸收无明显的促进作用。与一般制剂相比,亚微乳剂可以提高肉桂酸的血药浓度。
Objective To study the pharmacokinetics of styrax in different combinations and formulations after oral administration in SD rats.Methods Styrax,erxianghuoxin(traditional Chinese medicines)soft capsules(ER)and erxiang submicron emulsion(EM)were administrated orally to SD rats separately.The UPLC-MS/MS method was used to determine the concentrations of cinnamic acid in rat plasma.Pharmacokinetic parameters were obtained by the drug and statistics(DAS)version 2.0 software.Differences in pharmacokinetics of cinnamic acid were analyzed by the Student′s t-test using SPSS statistics software.Results After oral administration of styrax and ER,the pharmacokinetics parameters AUC0-t,AUC0-∞,ρmax,tmax,V of cinnamic acid showed no significant differences(P>0.05);but after oral administration of EM,ρmax and tmax increased,V decreased significantly(P<0.05),other parameters had no significant difference.After co-administration of styrax and lignum dalbergiae odoriferae oil,the pharmacokinetics parameters of the cinnamic acid showed no significant differences compared with that in styrax;but the sub-emulsion improved the cinnamic acid plasma concentrations and decreased the apparent volume of distribution.Conclusions Lignum dalbergiae odoriferae oil has no significant affection in promoting the oral absorption of cinnamic acid.Submicron emulsion can improve the plasma concentration of cinnamic acid.

关键词(KeyWords)： 苏合香;肉桂酸;亚微乳剂;药动学;UPLC-MS/MS色谱法
styrax;cinnamic acid;submicron emulsion;pharmacokinetics;UPLC-MS/MS method

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 张博,刘晓娜,周越,胡丽萍
ZHANG Bo1,LIU Xiao-na2,ZHOU Yue1,HU Li-ping1(1.School of Pharmacy

DOI: 10.14066/j.cnki.cn21-1349/r.2012.04.003

参考文献(References)：

• [1]《全国中草药汇编》编写组.全国中草药汇编:下册[M].北京:人民卫生出版社,1978:301.
• [2]罗光明,龚千峰,刘贤旺.苏合香研究进展[J].江西中医学院学报,1997,9(1):43-44.
• [3]李坤.苏合香化学成分及药理学研究进展[J].山东医学高等专科学校学报,2010,32(6):413-414.
• [4]朱亮,冷红文,谭力伟.苏合香抗血栓作用[J].中成药,1990,12(9):31-32.
• [5]郭丽冰,王蕾,廖华卫.降香CO2超临界萃取物的GC-MS分析[J].广东药学院学报,2003,3(1):12-13.
• [6]訾慧,沙明.中药降香研究进展[J].辽宁中医学院学报,2003,5(2):90-91.
• [7]ZHANG Jun,CHEN Min,JU Wen-zheng,et al.Liquidchromatograph/tandem mass spectrometry assay for thesimultaneous determination of chlorogenic acid and cin-namic acid in plasma and its application to a pharmaco-kinetic study[J].Journal of Pharmaceutical and Bio-medical Analysis,2010,51:685-690.
• [8]阳长明,侯世祥,孙毅毅,等.保心微丸中肉桂酸大鼠体内的药代动力学研究[J].中草药,2011,32(7):616-618.
• [9]张军,陈玟,居文政,等.脉络宁注射液中肉桂酸血药浓度的LC-MS/MS测定及人体药动学研究[J].中国中药杂志,2010,35(14):1887-1891.
• [10]李培凡,张韻慧,肖莉,等.中药复方苏冰口崩片中肉桂酸在大鼠体内的HPLC测定及药动学研究[J].中国中药杂志,2007,32(23):2528-2530.
• [11]戴荣华,宋宗华,鞠涛,等.滋肾丸中肉桂酸在大鼠体内的测定及药动学研究[J].中国药学(英文版),2004,13(2):130-133.
• [12]孙捷,郝福,蒋晔,等.冠心苏合丸中肉桂酸的大鼠小肠吸收动力学[J].华西药学杂志,2008,23(1):71-73.
• [13]唐晓荞,杨祥良.灯盏花素磷脂复合物改善大鼠小肠吸收的研究[J].中国中药杂志,2005,30(3):222-225.
• [14]王道刚,张钰琴,凌江红.醒脑开窍方药的实验研究进展[J].医学研究杂志,2010,39(5):110-112.
• [15]KAKEMI K,SEZAKI H,MURANISHI S,et al.Mecha-nism of intestinal absorption of drugs from oil in wateremulsion[I].Chem Pharm Bull,1972,20:708-714.
• [16]李文兰,杜娟,季宇彬,等.肉桂酸的代谢与CYP450酶的相关性研究[J].中国药学杂志,2009,44(4):266-270.
• [17]SARASQUETE C,SEGNER H.Cytochrome P4501ACYP1A in teleostean?shes.A review of immunohisto-chemical studies[J].The Science of the Total Environ-ment,2000,(247):313-332.