α细辛醚体外经皮扩散实验及其评价

α细辛醚(αasarone)是中药石菖蒲的有效成分之一,国内自1978年从石菖蒲挥发油中提取出α细辛醚单体以来,经广泛的药理和临床研究证明,α细辛醚具有显著镇静、平喘、祛痰、抗癫等作用。另外也有文献报道α细辛醚有降脂作用[1]。目前α细辛醚的胶囊、片剂和注射液被广泛应用于临床,但是,无论胶囊还是片剂,α细辛醚的生物利用度都是很低的[2],其绝对生物利用度均低于5%,同时对α细辛醚毒理学研究表明,当α细辛醚>182.5mg/kg时有致畸作用[3]。根据α细辛醚的性质及透皮给药的优点,我们想研制一种α细辛醚透皮给药制剂,以求达到持续、稳定、可靠…     

石菖蒲-远志药对配对前后水煎液中挥发性成分的含量变化分析

目的研究经典药对石菖蒲-远志配伍前后水煎液中挥发性成分的含量变化。方法煎煮法分别获得石菖蒲-远志药对和单味药材的水煎液,气相色谱法(GC)测定水煎液中α-细辛醚和β-细辛醚的含量。结果石菖蒲-远志药对中α-细辛醚的含量为0.048%,β-细辛醚的含量为0.812%;石菖蒲单煎中α-细辛醚的含量为0.049%,β-细辛醚的含量1.012%;结论石菖蒲、远志配伍后,α-细辛醚含量无明显变化,β细辛醚含量显著降低(P<0.05)。     

石菖蒲α-细辛醚对Lithium-Pilocarpine癫痫模型GABA系统的调控作用

目的探讨石菖蒲α-细辛醚治疗对Lithium-Pilocar-pine模型大鼠抗癫痫作用可能的分子机制。方法建立Lithium-Pilocarpine模型,通过观察α-细辛醚治疗对Lithium-Pilocarpine模型大鼠GABA含量、GAD67表达、GABA-T活性及GABAA受体表达的影响。结果①模型组大鼠癫痫持续状态(Status epilepticus,SE)后12 h～24 h海马GABA含量及GAD67表达明显降低(P<0.01),持续至SE后72 h,之后缓慢增高;②SE后各时相脑内GABA-T活性明显增高(P<0.01),以海马区GABA-T活性增高最为突出,持续至SE后1周仍明显高于正常对照组;③SE后12 h～24 h脑内GABAAR-mRNA表达明显降低,GABAAR-mRNA表达高峰主要发生在SE后48 h～72 h;④石菖蒲α-细辛醚治疗能显著增加大鼠SE后各时相海马GABA含量,增强GAD67及GABAA-RNA表达,并持续数日以上,至SE后1周恢复正常;能降低SE后增高的GABA-T活性,其下调海马区GA-BA-T活性的作用强于额叶。结论石菖蒲α-细辛醚可能通过抑制GABA-T活性以降低GABA分解代谢,上调GAD67表达使GABA合成增加,上调GABAA受体表达以增强GA-BA介导的抑制功能来发挥抗癫痫作用。     

HPLC-荧光法测定α-细辛醚热熔压敏胶贴剂的相对生物利用度

目的:建立家兔血浆内α-细辛醚的HPLC-荧光测定法,研究α-细辛醚热熔压敏胶贴剂在家兔体内的相对生物利用度。方法:家兔给予α-细辛醚混悬液或α-细辛醚贴剂后于不同时间点采血,血浆样品处理后以甲醇-水(75∶25)为流动相,使用ZORBAX Eclipse XDB-C18色谱柱(250 mm×4.6 mm,5μm)进行分离,流速1.0 mL·min-1,荧光检测器激发波长为265 nm,检测波长为365 nm,测定血浆药物浓度,计算药物动力学参数和相对生物利用度。结果:α-细辛醚在浓度0.01～1μg.mL-1(r=0.9998)范围内线性关系良好,检测限为0.005μg·mL-1,方法学回收率为96.2%～102.0%,日内与日间RSD均<4.5%。家兔口服α-细辛醚混悬液后的AUC0→t为(0.53±0.23)μg.h·mL-1,贴剂给药的AUC0→t为(7.86±2.15)μg.h·mL-1,贴剂的相对生物利用度为1494%。结论:该法简便准确,可用于家兔血浆内α-细辛醚浓度的测定;α-细辛醚热熔压敏胶贴剂的相对生物利用度高。     

高效液相色谱法测定细辛属药材中α-细辛醚含量

目的 建立细辛药材中α-细辛醚的定量分析 方法 ,同时对不同来源细辛商品药材进行α-细辛醚含量测定,为细辛药材的质量分析提供参考. 方法 采用高效液相色谱（HPLC）法对来源于我国9个省市（直辖市）36批次细辛药材进行含量测定, Krouasil C18色谱柱（4.6 mm×250 mm,5 μm）;流动相：甲醇-磷酸二氢钾溶液 （55：45）;流速：0.8 mL&#8226;min-1;检测波长：313 nm. 结果 各地区α-细辛醚含量差异较大,最高含量为129.2 μg&#8226;g-1,8批次含量未检出. 结论 建立的α-细辛醚含量测定方法简便、快捷、重复性好,可为细辛药材质量分析提供参考.     

石菖蒲α-细辛醚抗癫痫作用的实验研究

目的探讨石菖蒲成分α-细辛醚的抗癫痫作用。方法采用MES、MST及Lithium-pilocarpine模型;预先给予不同剂量的α-细辛醚,2次/d,连续28d,记录发作潜伏期、发作级别及惊厥动物数,对比观察α-细辛醚在控制3种模型癫痫发作中的疗效。结果石菖蒲α-细辛醚能对抗MES、MST模型小鼠及Lithium-pilocarpine模型大鼠的惊厥发作,抗惊厥率分别为40%～100%、50%～90%、40%～80%;能明显延长MST模型小鼠及Lithium-pilocarpine模型大鼠惊厥发作潜伏期,分别为70～180s和4～15min;并能降低Lithi-um-pilocarpine模型大鼠惊厥发作级别达1.96。结论石菖蒲α-细辛醚具有确切的抗癫痫作用,是一种广谱抗癫痫药。     

石菖蒲不同提取物化学成分的GC-MS分析

本文用气相色谱-质谱(GC-MS)方法分析了石菖蒲不同提取物(挥发油、水提液、去油水提液)的化学成分,结果表明:石菖蒲挥发油中除β-细辛醚相对含量高外,相对含量较高的成分还有α-细辛醚、顺式甲基异丁香酚、榄香素(烯),反式甲基异丁香酚、菖蒲二烯、石竹烯、柏木烯等;水提液中检出了石菖蒲挥发油的3个主要成分,几乎未检出α-细辛醚;去油水煎液中发现一特征成分,由于现有的谱库中未能检索到,故未能鉴定.研究结果为进一步开发石菖蒲提供依据.     

石菖蒲不同提取物化学成分的GC-MS分析

本文用气相色谱-质谱(GC-MS)方法分析了石菖蒲不同提取物(挥发油、水提液、去油水提液)的化学成分,结果表明石菖蒲挥发油中除β-细辛醚相对含量高外,相对含量较高的成分还有α-细辛醚、顺式甲基异丁香酚、榄香素(烯),反式甲基异丁香酚、菖蒲二烯、石竹烯、柏木烯等;水提液中检出了石菖蒲挥发油的3个主要成分,几乎未检出α-细辛醚;去油水煎液中发现一特征成分,由于现有的谱库中未能检索到,故未能鉴定.研究结果为进一步开发石菖蒲提供依据.     

α-细辛醚抗癫痫作用的实验研究

目的观察α-细辛醚对Lithium-pilocarpine模型大鼠的抗癫痫作用及对其学习记忆能力的影响。方法观察不同剂量α-细辛醚对癫痫模型皮层脑电图、癫痫自发与反复发作(SRS)及学习记忆能力的影响。结果α-细辛醚可延长SRS潜伏期,减少SRS数量及发作严重程度(P<0.05);能显著延长痫性放电潜伏期,降低痫性放电频率(P<0.05);能显著降低水迷宫训练的平均潜伏期,改善大鼠对平台空间位置记忆储存及提取再现能力(P<0.05);其作用有剂量依赖性,以200 mg.kg-1作用最强。结论α-细辛醚能显著改善大鼠癫痫模型学习记忆能力,其机制可能与控制癫痫发作及抑制癫痫放电有关。     

α-细辛醚大鼠在体肠吸收动力学研究

目的研究α-细辛醚的大鼠肠吸收机制。方法运用大鼠在体单向灌流法进行肠吸收实验,收集灌流流出液,测定其质量,采用高效液相色谱法(HPLC)测定灌流液中α-细辛醚的含量,利用质量法计算动力学参数。结果α-细辛醚在十二指肠、空肠、回肠段的吸收速率常数(Ka)和表观吸收系数(Papp)差异均无统计学意义(P>0.05),灌流速度对药物的Ka和Papp有显著影响(P<0.05),药物浓度在一定范围内对Ka和Papp均无明显影响(P>0.05)。结论α-细辛醚在整个肠道均有吸收,在大鼠肠道的吸收呈现一级动力学特征,且吸收机制为被动扩散。     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Emerging drugs for epilepsy

Epilepsy affects ≤ 1% of the world's population. Antiepileptic drugs (AEDs) are the mainstay of treatment, although more than a third of patients are not rendered seizure free with existing medications. Uncontrolled epilepsy is associated with increased mortality and physical injuries, and a range of psychosocial morbidities, posing a substantial economic burden on individuals and society. Limitations of the present AEDs include suboptimal efficacy and their association with a host of adverse reactions. Continued efforts are being made in drug development to overcome these shortcomings employing a range of strategies, including modification of the structure of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening of compounds in traditional and newer animal models. This article reviews the need for new treatments and discusses some of the emerging compounds that have entered clinical development. The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals.     

盐酸达泊西汀中甲磺酸甲酯、甲磺酸乙酯及甲磺酸异丙酯的顶空毛细管GC-ECD法测定

建立了衍生化顶空毛细管气相色谱-电子捕获检测器(ECD)法测定盐酸达泊西汀中的甲磺酸甲酯(MMS)、甲磺酸乙酯(EMS)和甲磺酸异丙酯(IMS).应用碘化钠衍生技术,使用PW-5毛细管柱,载气为氮气,ECD检测,程序升温.MMS、EMS和IMS分别在0.03～0.30、0.05～0.50和0.05～0.50 μg/ml浓度范围内线性关系良好,平均回收率分别为63.5％、100.3％和96.2％,最低检测限分别为0.30、0.50和0.50 ng/ml.     

血管内皮生长因子的异常与子(癎)前期发病的关系

目的:研究血浆可溶性细胞间黏附分子-1(sICAM-1)浓度和胎盘组织血管内皮生长因子(VEGF)、胎盘生长因子(PLGF)及其血管内皮生长因子受体1(VEGFR1,Flt-1)、可溶性血管内皮生长因子受体1(sVEGFR1,sFlt-1)mRNA的表达与子前期的关系.方法:采用酶联免疫吸附测定法(ELISA)检测45例子前期患者和45例健康产妇血清sICAM-1的浓度,逆转录-聚合酶链反应(RT-PCR)方法检测胎盘组织中VEGF、PLGF、Flt-1、sFlt-1 mRNA的表达.结果:(1)子前期组sICAM-1水平为(218.45±29.93) μg/L,显著高于对照组的(168.84±19.39) μg/L(P < 0.01).(2)子前期患者胎盘组织VEGF、PLGF、Flt-1、sFlt-1 mRNA的相对表达量显著高于对照组(均P < 0.01).(3)血清sICAM-1浓度与胎盘组织中sFlt-1mRNA的相对表达量呈正相关(r = 0.90,P < 0.01).结论:子前期患者血清sICAM-1浓度升高,其胎盘组织VEGF、PLGF、Flt-1、sFlt-1 mRNA的相对表达量也升高.胎盘组织sFlt-1mRNA的高表达与子前期内皮损伤等有密切关系.     

Antiparasitic protozoan vaccines

Parasitic infections caused by pathogenic protozoa affect over 1 billion people worldwide and impose a substantial health and economic burden, particularly on inter-tropical less-developed countries where they are more prevalent. Despite encouraging progress in vaccine development, chemotherapy remains the single most effective, efficient and inexpensive means to control most parasitic infections [1]. However, day to day parasites are becoming increasingly resistant to drugs currently in use, such as Plasmodium towards chloroquine, lending to the start of a promising future for vaccines. Patent applications regarding vaccines for the prevention, control and diagnosis of parasitic protozoan infections are reviewed for the period December 1996 - October 2000. However, vaccines for some of the protozoan infections do not appear in the literature in the period reviewed; only, vaccines against malaria, leishmaniasis, trypanosomiasis, cryptosporidiosis, pneumocystosis, eimeriosis, toxoplasmosis and neosporosis, as well as Babesia microti infections have been found.     

Binding affinity in drug design: experimental and computational techniques

ABSTRACT

Introduction: In pharmaceutical design where future drugs are developed by targeting a specific chosen protein, the evaluation of ligand affinity is crucial. For this very purpose are a multitude of diverse methods which are continuously being improved, which, in turn, makes it difficult to choose which techniques to use in practice.

Areas covered: In this review, the authors discuss both experimental and computational approaches for affinity evaluation. Basic principles, general limitations and advantages, as well as main areas of application in drug discovery, are overviewed for some of the most popular ligand binding assays. The authors further provide a guide to affinity predictions, collectively covering several techniques that are used in the first stages of rational drug design.

Expert opinion: All affinity estimation methods have limitations and advantages that partially overlap and complement one another. Some of the suggested best practices include cross-verification of data using at least two different techniques and careful data interpretation.