【作者】 申涛；

【导师】 赵怀清；

【作者基本信息】 沈阳药科大学 ， 药物分析学， 2008， 硕士

【摘要】 畅鼻通颗粒（宁金冲剂）收载于中药部颁标准17册,由桂枝、当归、荆芥、防风、黄芩、白芍、薄荷和甘草等八味药材组成,具有调和营卫,解表散风之的功效,主要用于风干风寒感冒,营卫不和,恶风有汗,头痛,喷嚏,鼻塞及过敏性鼻炎:,荨麻疹等过敏性疾患见上述证候者。本文以畅鼻通颗粒为研究对象,在原有标准的基础上完善了畅鼻通颗粒的质量控制方法,并进行了其指标成分桂皮酸在大鼠体内的药物动力学研究。采用薄层色谱法（TLC）法,对处方中防风、当归、黄芩、荆芥和甘草等五味药材进行了鉴别。采用高效液相色谱法（HPLC）法,建立了桂皮酸、黄芩苷、黄芩素、升麻素苷、5-O-甲基维斯阿米醇苷、芍药苷和甘草酸的含量测定方法,线性范围分别为:0.82～8.2μg·mL^-1（r=0.999 9）,31.0～310.0μg·mL^-1（r=0.999 9）,3.2～32.0μg·mL^-1（r=0.999 7）,2.4～24.0μg·mL^-1（r=0.999 9）,2.4～24.0μg·mI^-1（r=0.999 9）,10.8～108.0μg·mL^-1（r=0.999 8）和7.0～56.0μg·mLq（r=0.999 7）;回收率分别为:101.1%（RSD=2.2%）,100.5%RSD:2.0%),101.4%（RSD:1.9%）,100.1%（RSD=1.5%）,100.7%（RSD=1.9%）,100.4%（RSD=2.0%）和99.4%（RSD=1.9%）。结果表明,在上述范围内各组分浓度与峰面积线性关系良好,所建立的测定方法简便,重复性好,为评价畅鼻通颗粒的质量提供了依据。建立了大鼠灌胃给予畅鼻通颗粒后,血浆中桂皮酸的含量测定方法。色谱条件采用Diamonsil^TMC₁₈柱（200mm×4.6mm,51μm）色谱柱,以甲醇-乙腈-0.5%冰醋酸溶液（39∶20∶60,v/v/v）为流动相,流速1.0mL·min^-1,检测波长280nm,柱温35℃。桂皮酸的线性范围为0.06～6.0μg·mL^-1（r=0.998 8）,提取回收率分别为84.9%、82.1%和87.0%,日内和日间精密度RSD均小于5.8%。本方法专属性强,重现性好,操作简便。采用该分析方法,进行桂皮酸在大鼠体内的药动学研究。大鼠单剂量灌胃给予畅鼻通颗粒后,主要药动学参数分别为:C_max0.87±0.16μg·mL^-1,T_max0.167±0.053h,t_1/28.62±2.00h,Ke 0.085±0.022 h^-1,AUC_0-t3.68±1.51μg·h·mL^-1,AUC_0-∞4.51±1.54μg·h·mL^-1。更多还原

【Abstract】 Changbitong granule,which has been included in the drug standard of ministry of public health of PRC,consists of eight herbs:Cinnamomum cassia（Guizhi）, Schizonepeta tenuifolia（Jingjie）,Saposhnikovia divaricata（Fangfeng）,Scutellaria baicalensis（Huangqin）,Angelica sinensis（Danggui）,Paeonia lactiflora（Baishao）, Mentha haplocalyx（Bohe）,Glycyrrhiza uralensis（Gancao）.It is used for the treatment of anaphylactic rhinitis,nasal obstruction,stemutation,headache and urticaria.In this dissertation,several methods for quality control have been developed to improve the drug standard of Changbitong granule,and the pharmacokinetics of cinnamic acid has been stuied in rats.Five medical materials in Changbitong granule,including Saposhnikovia divaricata （Fangfeng）,Angehca sinensis（Danggui）,Scutellaria baicalensis（Huangqin）, Schizonepeta tenuifolia（Jingjie）,Glycyrrhiza uralensis（Gancao）,were identified by thin layer chromatography（TLC）.High performance liquid chromatography（HPLC） methods were established to determine the contents of cinnamic acid,baicalin,baicalein, prim-O-glucosylcimifugin,4’-O-β-D-glucosyl-5-O-methylvisamminol,peoniflorin and glycyrrhizic acid in Changbitong granule.The determination could be accomplished by different mobile phase system on Diamonsil C₁₈columns.The linear ranges were 0.82～8.2μg·mL^-1（r = 0.999 9）,31.0～310.0μg·mL^-1（r = 0.999 9）,3.2～32.0μg·mL^-1（r= 0.999 7）,2.4～24.0μg·mL^-1（r = 0.999 9）,2.4～24.0μg·mL^-1（r = 0.999 9）,10.8～108.0μg·mL^-1（r = 0.999 8）and 7.0～56.0μg·mL^-1（r = 0.999 7）,respectively.The recoveries were 101.1%（RSD = 2.2%）,100.5%（RSD = 2.0%）,101.4%（RSD = 1.9%）, 100.1%（RSD = 1.5%）,100.7%（RSD = 1.9%）,99.8%（RSD = 1.7%）and 99.4%（RSD = 1.9%）,respectively.The assay methods are simple,rapid and reproducible,which provide a,quantitative basis for the quality assessment of Changbitong granule.An HPLC-UV method was developed for the determination of cinnamic acid in rat plasma.The analysis was performed on a Diamonsil^TMC₁₈（200 mm×4.6 mm,5μm） column with acetonitrile-methanol-0.5%acetic acid（39:20:60,v/v/v）as the mobile phase at the flow rate of 1.0 mL·min^-1.The UV detection wavelength was set at 280 nm. The extraction recoveries at the concentration of 0.12,0.60 and 4.80μg·L^-1were 84.9%, 82.1%and 87.0%,respectively.A linear calibration was obtained in the concentration range from 0.06 to 6.00μg.mL^-1（r = 0.998 8）.Intra-day and inter-day precision（RSD） were both less than 6.0%.The method was proved to be accurate and simple,and was applied to the pharmacokinetic study of cinnamic acid in rats after i.g.administration of Changbitong granule.The main pharmacokinetic parameters were achieved as follows: C_max0.1674±0.053μg·mL^-1,T_max0.87±0.16 h,t_1/28.62±2.00 h,K_e 0.085±0.022 h^-1, AUC_0-t3.68±1.51μg·h·mL^-1,AUC_0-∞4.51±1.54μg·h·mL^-1.更多还原