牛蒡子苷代谢动力学与分布研究

目的研究牛蒡子苷代谢动力学与分布。方法单剂量随机灌胃,高效液相色谱法测定大鼠体内牛蒡子苷浓度及其在脏器中的分布,代谢动力学分析采用3P87软件。结果口服牛蒡子苷300 mg/kg在大鼠体内呈二室模型分布,其主要动力学参数为A=(37.374 5±8.964 7)μg·mL^-1;B =(6.210 6±1.489 3)μg·mL^-1;α=(0.004 3±0.000 9)min^-1;β=(0.000 4±0.000 2)min^-1;K_α==(0.420 2±0.167 5)min^-1;t_1/2α=(115.192 6±14.382 4)min ;t_1/2β=(1 485.578 1±161.173 3)min;K₁₀=(0.001 0±0.000 4)min^-1;K₂₁=(0.001 4±0.000 6)minn^-1;K₁₂=(0.002 3±0.001 3)min-1;C_max=(41.786 3±7.521 7)μg·mL^-1;T_max=(9.891 9±4.341 4)min;AUC =(22 503.272 7±4 120.182 8)μg·min·mL^-1。牛蒡子苷在心、肝、肾、脑等脏器也有分布,以肝脏中最高。结论高效液相色谱法测定牛蒡子苷在动物体内代谢变化,快速、受杂质干扰小,且稳定性和重现性较好,适合牛蒡子苷代谢产物含量测定。牛蒡子苷在体内吸收很快,消除也快。     

牛蒡子中牛蒡苷和牛蒡苷元的测定

目的：测定牛蒡子中牛蒡苷和牛蒡苷元的含量。方法采用 Agilent-C18（4.6mm ×250mm,5μm）色谱柱;流动相：甲醇-水二元梯度洗脱,流速0.8mL· min －1,检测波长280nm。结果牛蒡苷和牛蒡苷元分别在0.36～2.8μg（r＝0.9995）,0.006～0.56μg（r＝0.9996）范围内线性关系良好。平均回收率牛蒡苷为100.3％,RSD为2.3％;牛蒡苷元为99.5％,RSD为2.9％。结论该方法简便、准确,实验结果可为牛蒡子的质量控制提供参考。     

牛蒡子水煎液、牛蒡苷和牛蒡苷元体外抗菌实验

目的:对照研究牛蒡子水煎液、牛蒡苷和牛蒡苷元的体外抗菌作用.方法:采用系统溶剂提取法提取牛蒡苷,再用水浴水解法制得牛蒡苷元,以双黄连粉针为对照,用纸片扩散法进行抗菌实验.结果:牛蒡苷元和双黄连粉针的抑菌圈直径均大于15 mm,对5种菌株均有高度敏感,具有很强的抑菌能力.牛蒡苷的抑菌圈稍小,直径为10～14 mm,但也比较明显,属于中等敏感,抑菌能力良好.浓度为2:1、1:1和1:2的牛蒡子水煎液的抑菌圈较小,直径均小于10mm,属于低度敏感,抑菌能力较差.稀释至1:4的牛蒡子水煎液,对试验菌株基本无抑菌效果.结论:牛蒡子具有一定的抗菌作用,可以开发为一种新型的抗感染药物.     

牛蒡子中牛蒡苷的含量考察

采用HPLC法考察了15批牛蒡子中牛蒡苷的含量，结果牛蒡苷平均含量为8．4％，方法回收率为101．2％（n＝5）。     

牛蒡子中牛蒡子苷元的分离及结构表征

目的：从牛蒡子中分离纯化出有效成分,并对其分子结构进行鉴定与表征。方法：采用醇提酸解法提取,分离出粗品,经过对粗品进行脱脂、结晶处理,得到无色棱状晶体。采用紫外光谱（UV）、红外光谱（FTIR）、质谱（MS）、氢谱（H-NMR）、碳谱（C-NMR）及单晶衍射对该有效成分进行组成和分子结构的鉴定与表征。结果：从牛蒡子粗粉中经提取分离,得到结晶,提取率为4.46%,显色反应及波谱分析均显示为木脂素类化合物。结论：该有效成分鉴定为牛蒡子苷元,即（3R,4R）-4-[（3,4-二甲氧基苯基）甲基]二氢-3-[（4-羟基-3-甲氧基苯基）甲基]-2（3H）-呋喃酮,分子式为C21H24O6。     

复方牛蒡子含片水提工艺优选与牛蒡子苷含量变化研究

目的优选复方牛蒡子含片最佳水煎工艺,并考察各工艺步骤中牛蒡子苷的含量变化情况。方法以牛蒡子苷提取量为指标,采用正交试验优选影响水煎工艺的主要因素,并对水煎浓缩液、醇沉液及干浸膏中牛蒡子苷进行含量测定。结果优选出牛蒡子最佳水煎工艺为加水12倍,煎煮3次,每次1h,牛蒡子苷在各工艺步骤均有一定量损失。结论本实验为复方牛蒡子含片的生产提供了可靠数据。     

复方牛蒡子含片水提工艺优选与牛蒡子苷含量变化研究

目的 优选复方牛蒡子含片最佳水煎工艺,并考察各工艺步骤中牛蒡子苷的含量变化情况。方法 以牛蒡子苷提取量为指标,采用正交试验优选影响水煎工艺的主要因素,并对水煎浓缩液、醇沉液及干浸膏中牛蒡子苷进行含量测定。结果 优选出牛蒡子最佳水煎工艺为加水12倍,煎煮3次,每次1 h,牛蒡子苷在各工艺步骤均有一定量损失。结论 本实验为复方牛蒡子含片的生产提供了可靠数据。     

牛蒡子饮片与粉末煎煮过程中牛蒡苷含量变化的比较研究

目的:比较牛蒡子饮片与粉末在煎煮过程中牛蒡苷含量的变化.方法:采用HPLC法,测定牛蒡子饮片和粉末在不同煎煮时间煎液中牛蒡苷含量.结果:从2～60 min煎煮过程中,不同时间点牛蒡子粉末煎液中的牛蒡苷含量及煎出率均高于牛蒡子饮片煎液,均有极显著性差异(P＜0.01).结论:从化学成分层次,验证了中药煮散省材省时之优点,为中药传统饮片应用形式的创新提供了新思路.     

HPLC研究异牡荆苷在大鼠体内的药代动力学及组织分布(英文)

本文建立了异牡荆苷在大鼠血浆及不同组织中的高效液相色谱检测方法,采用RP-C₁₈色谱柱（250mm×4.6mm,5.0μm）,以甲醇-1%冰醋酸溶液（40:60,v/v）为流动相,柱温为30℃,检测波长为338nm。通过专属性、精密度、线性、准确度、稳定性、提取回收率、最低定量限等方法学考察,证实本方法可对血浆及不同组织中的异牡荆苷进行准确检测。在此方法的基础上研究了异牡荆苷在大鼠体内的药代动力学及组织分布特征。大鼠在静脉注射异牡荆苷后,在预定的时间点取样检测。结果显示异牡荆苷在高、中、低剂量（18.75,3.75,0.75mg/kg）药代动力学特征符合二室模型,在所研究的剂量范围内AUC与给药剂量呈现良好的线性相关性,符合线性动力学特征。药物t_1/2α为1.54-1.84min,t_1/2β为36.94-46.27min。异牡荆苷在组织中的浓度分布从高到低分别为肾>肝>肺≈卵巢>心≈脾>脑。     

牛蒡子浸膏的稳定性研究

目的确定牛蒡子浸膏的干燥条件。方法在不同的干燥温度和时间下,测定牛蒡子浸膏中有效成分牛蒡苷的含量。结果在80℃干燥48h后,牛蒡子浸膏有效成分牛蒡苷的损失较小,而在100℃烘48h后牛蒡苷的含量约下降了20．00％。结论牛蒡子浸膏的干燥温度应控制在80℃以下。     

牛蒡子苷对血瘀大鼠血液流变学的影响

目的研究牛蒡子苷对血瘀大鼠血液流变学和血栓凝血因子的影响。方法测定口服不同剂量的牛蒡子苷后对血瘀证大鼠流变学、F ib、aPTT和PT的影响。结果牛蒡子苷可以明显降低急性血瘀大鼠全血黏度,红细胞聚集指数,红细胞刚性指数和还原黏度,明显延长血瘀大鼠PT和aPTT时间,降低F ib浓度。结论牛蒡子苷能显著改善血瘀证大鼠血液流变学和抗凝血作用。     

HPLC法测定羚羊感冒颗粒中的牛蒡子苷含量

目的:建立羚羊感冒颗粒中牛蒡子苷的含量测定方法。方法:采用Waters2695泵,Waters2487检测器,乙腈-水(25:75)为流动相;检测波长:278nm;流速:0.5mL.min-1;柱温:35℃。结果:进样量0.29888μg～3.7360μg范围内,呈良好的线性关系,r=0.9999(n=6);平均回收率为104.6%,RSD为1.00%(n=6)。结论:本法操作简便,准确,快速,可用于羚羊感冒颗粒的质量控制。     

Pharmacokinetic concepts — Drug binding,apparent volume of distribution and clearance

Summary Blood flow rate-limited physiological pharmacokinetic models have been used to examine the relationship between apparent volume of distribution and clearance or, more specifically between drug binding in blood, eliminating regions or noneliminating regions and clearance. The influence of binding on drug elimination depends on the driving force concentration in the eliminating region. In most instances this is likely to be free drug concentration in the region. Under these conditions, the results indicate that apparent volume of distribution and drug clearance from the blood should be treated as independent pharmacokinetic variables. Volume of distribution per se has no effect on clearance or on average steady-state blood levels. Drug binding in nonvascular regions (i. e. tissue binding) seems to be of limited importance except as a determinant of half-life. Although changes in tissue binding will affect partition coefficient and apparent volume of distribution, such changes will have no effect on average steady-state blood levels of either total or free drug.     

高效液相色谱法测定银翘解毒颗粒中绿原酸和牛蒡苷的含量

目的建立高效液相色谱法测定银翘解毒颗粒中绿原酸和牛蒡苷的含量。方法采用Agilent ZORBAX SB-C18(4.6 mm×150 mm,5μm)色谱柱,以1%的磷酸溶液-甲醇为流动相进行梯度洗脱;流速1.0 mL.min-1;柱温40℃;检测波长:绿原酸为327 nm,牛蒡苷为280 nm。结果绿原酸在6.881~61.92μg.mL-1与峰面积呈良好的线性关系,平均回收率为98.9%,RSD为1.6%;牛蒡苷在13.84~124.6μg.mL-1与峰面积呈良好的线性关系,平均回收率为99.2%,RSD为1.1%。结论所建立的方法准确可靠、灵敏度高、专属性强,可有效控制银翘解毒颗粒的质量。     

高效液相色谱法测定小儿金丹片中橙皮苷和牛蒡苷的含量

目的:建立小儿金丹片中橙皮苷、牛蒡苷的含量测定方法。方法:Diamonsil-C_(18)色谱柱(250 mm×4.6 mm,5μm);流动相为甲醇-水(45:55);检测波长为284nm;进样量为10μL;柱温为室温;流速为1.0 mL·min~(-1)。结果:橙皮苷对照品在0.12～1.08μg范围内,进样量与峰面积间呈良好的线性关系,r=0.9999,平均回收率为99.2%;牛蒡苷对照品在0.16～1.44μg范围内,进样量与峰面积间呈良好的线性关系,r=0.9998,平均回收率为98.9%。结论:本方法操作简便,结果准确,重现性好,可作为该制剂的含量测定方法。     

Pharmacokinetic interaction of entinostat and lapatinib following single and co-oral administration in rats

Abstract

1.?Entinostat, also known as SNDX-275 or MS-275, is a novel, potent, orally bioavailable, class I selective histone deacetylase inhibitor. Pre-clinical data has show that MS-275 can enhance the activity of lapatinib in HER²⁺ metastatic inflammatory and non-inflammatory breast cancer. This study examined whether oral administration of MS-275 to the rats with lapatinib led to any pharmacokinetic interactions.

2.?To evaluate pharmacokinetic interaction of MS-275 and lapatinib in rat, a sensitive and simple LC-MS method was developed to simultaneously determine MS-275 and lapatinib in rat plasma with carbamazepine as internal standard (IS). Eighteen rats were divided randomly into three groups, lapatinib group (lapatinib 15?mg/kg, n?=?8), MS-275 group (MS-275 15?mg/kg, n?=?8) and co-administration group (MS-275 15?mg/kg and lapatinib 15?mg/kg, n?=?8).

3.?There was no statistical pharmacokinetics difference for MS-275 in MS-275 group and co-administration group; the lapatinib could not influence the pharmacokinetic profile of MS-275 in rats. However, there is a statistical pharmacokinetics difference between lapatinib in the lapatinib group and co-administration group, when co-oral administration MS-275 with lapatinib, AUC increased from 2375.5 to 9900.3?ng/mL h (p?<?0.05), C_max increased from 538.0 to 2578.2?ng/mL (p?<?0.01), CL decreased from 6.2 to 1.7?L/h/kg (p?<?0.01).

4.?These data indicate MS-275 could obviously influence the pharmacokinetic profile of lapatinib in rats, which might cause drug–drug interactions in humans when using lapatinib with MS-275. Further investigations should be carried out to elucidate the synergistic mechanisms between the two drugs.     

脑组织生理药代动力学模型研究进展

在新药研发过程中,了解药物在脑内的转运与分布情况可以预测药物效应和不良反应。然而,人脑内的药物浓度难以通过现有分析技术直接测定。生理药代动力学（PBPK）模型通过数学建模的方式模拟药物在脑内的转运与分布情况,为预测脑内药物浓度提供帮助。综述影响药物在脑内转运分布的生理因素,以及近年来文献中报道的研究药物脑组织分布的PBPK模型及其在药物研发中的应用。     

Pharmacokinetic behavior and tissue distribution of verapamil and its enantiomers in rats by HPLC

The differences in pharmacokinetic behavior and tissue distribution of verapamil and its enantiomers were investigated in rats. In high-performance liquid chromatographic method, an achiral ODS column (150 mm x 4.6 mm i.d.) with the mobile phase consisting of methanol-water (73:30, v/v) was used for the determination of the concentration for racemic verapamil, and a Chiralcel OJ column (250 mmx4.6 mm i.d.) with the mixture of n-haxane-ethanol-triethylamine (85:15:0.2, v/v/v) as mobile phase was used to determine the concentrations of verapamil enantiomers. A fluorescence detector in the analytical system was set at excitation and emission wavelengths of 275 nm and 315 nm. The differences between enantiomers were apparent in the pharmacokinetics in rats. The area under the concentration-time curve (AUC) of S-(-) verapamil was higher than that of R-(+) verapamil. The half-distribution time (T 1/2(alpha)) of S-(-) verapamil which distributing to tissue from blood was shorter than that of R-(+) verapamil, but the elimination half-time (T 1/2(beta)) was longer in rat following oral administration of racemic verapamil. At 1.3 h after oral administration of racemic verapamil, however, there were no significant differences between enantiomers for the distributions in major tissues such as heart, cerebrum, cerebellum, liver, spleen and kidney.     

HPLC法测定凉血祛风糖浆中牛蒡苷的含量

目的:建立凉血祛风糖浆中牛蒡苷的含量测定方法。方法:用DiamonsilC18色谱柱(250mm×4.6mm,5μm,瑞士迪马);流动相:乙腈-水(25∶75);检测波长:280nm;流速:1.0mL·min-1。结果:牛蒡苷对照品在0.2472~1.2360μg范围内,进样量与峰面积间呈良好的线性关系,r=0.9998,平均回收率为99.36%。结论:本方法操作简便,结果准确,重现性好,可用于控制该制剂的质量。     

Pharmacokinetic behavior of huperzine A in plasma and cerebrospinal fluid after intranasal administration in rats

The aim of this study was to investigate the pharmacokinetic behavior of huperzine A (Hup A) in plasma and cerebrospinal fluid (CSF) after intranasal administration (0.5 mg/kg) in male Sprague‐Dawley rats. A pharmacokinetic study of intravenous Hup A (0.5 mg/kg) was also performed. The concentrations of Hup A in the biological samples were measured by high performance liquid chromatography–mass spectrometry. Blood samples were taken from the tail vein and CSF was sampled by cisternal puncture using a stereotaxic frame. The contribution of the olfactory pathway to the uptake of Hup A into CSF was determined by comparing the AUC_CSF/AUC_plasma ratios after intranasal and intravenous administration. The AUC ratios of intranasal to intravenous administration in CSF and plasma were 104% and 118%, respectively. No significant difference was observed between the AUC_CSF/AUC_plasma ratios of Hup A after intranasal administration (20%) and after intravenous infusion (23%). This indicated that approximately 20% of the Hup A level in plasma reached the CSF after both nasal and intravenous administration, and that no direct transport of Hup A from nose to CSF was found in rats. Copyright © 2009 John Wiley & Sons, Ltd.