响应面法优化胡柚幼果中柚皮苷与新橙皮苷的提取工艺

目的 优选胡柚幼果中柚皮苷与新橙皮苷的提取工艺。方法 在单因素试验的基础上,对乙醇浓度、料液比、提取时间3个因素进行响应面Box-Behnken中心组合设计优化,得到最佳提取工艺。结果 最佳提取工艺条件为乙醇浓度60%、料液比1：10、提取时间1.8 h、回流提取2次,在此条件下柚皮苷与新橙皮苷的总得率为23.44%。结论 本提取工艺方法简单、合理、稳定,为工业化生产提供了一定的依据。     

Simultaneous determination of danshensu,rosmarinic acid,cryptotanshinone, tanshinone IIA,tanshinone I and dihydrotanshinone I by liquid chromatographic–mass spectrometry and the application to pharmacokinetics in rats

A sensitive and specific liquid chromatography–tandem mass spectrometry method (LC–MS) was developed and validated for the separation and simultaneous determination of danshensu, rosmarinic acid and tanshinone compounds including cryptotanshinone, tanshinone I, dihydrotanshinone I and tanshinone IIA in rat plasma. Chromatographic separation of the analytes was successfully achieved on a C₁₈ column using a mobile phase composed of acetonitrile–water containing 0.5% glacial acetic acid. This method demonstrated good linearity and did not have endogenous material interfering with the active compounds and I.S. peaks. The limit of quantification of danshensu, rosmarinic acid, cryptotanshinone, dihydrotanshinone I, tanshinone I and tanshinone IIA were 5, 0.75, 0.1, 0.1, 1 and 0.5 ng/mL. The average extraction recoveries of these analytes from rat plasma were all over 60%. The precisions determined from five days were all within 10%. This method has been successfully applied in the simultaneous quantification and the pharmacokinetic studies of these six compounds in animals which were orally administered with danshen preparations.     

Simultaneous determination of danshensu, ferulic acid, cryptotanshinone and tanshinone IIA in rabbit plasma by HPLC and their pharmacokinetic application in danxiongfang

A selective and sensitive reversed-phase high performance liquid chromatography method was developed and validated for the simultaneous determination of danshensu, ferulic acid, cryptotanshinone, and tanshinone IIA in rabbit plasma using p-hydroxybenzoic acid as internal standard. Liquid–liquid extraction was used for sample preparation. Chromatographic separation was successfully achieved on an Agilent HC-C₁₈ column using a mobile phase composed of methanol–water (from 20:80 to 80:20, v/v) containing 0.5% (v/v) glacial acetic acid. The mobile phase was employing gradient elution at a flow rate of 1.0 ml/min. The method showed good linearity and no endogenous material interfered with the marked compounds and I.S. peaks. The limit of quantification of danshensu, ferulic acid, cryptotanshinone, and tanshinone IIA were 0.1, 0.03, 0.05, and 0.05 μg/ml, respectively. The average extract recoveries of the four compounds from rabbit plasma were all over 60%. The precisions determined from 5 days were all within 10%. The established method has been successfully applied in the pharmacokinetic study and drug interaction of danshensu, ferulic acid, cryptotanshinone, and tanshinone IIA in rabbits after intravenous administration of danxiongfang, a useful compound preparation of traditional Chinese medicine.     

苯妥英钠对大鼠脑缺血再灌注损伤保护作用的实验研究

目的 :探讨苯妥英钠对实验性脑缺血再灌注损伤的保护作用。方法 :采用结扎大鼠双侧颈总动脉制作不完全脑缺血 4 5min再灌注 12 0min模型 ,观察苯妥英钠对脑组织ATP酶活性、脑组织线粒体琥珀酸脱氢酶 (SDH)活性以及超微结构病理变化的影响。结果 :苯妥英钠可明显增加脑组织ATP酶活性 ,增强SDH的活性 ,并可明显改善损伤病理变化。结论 :苯妥英钠对脑缺血再灌注有保护作用 ,其机制与其提高脑组织ATP酶活性、稳定细胞膜、线粒体膜、保护线粒体功能有关。     

HPLC梯度洗脱法测定氯替泼诺妥布霉素复方混悬滴眼液中氯替泼诺含量及有关物质

摘 要 目的： 建立HPLC梯度法测定氯替泼诺妥布霉素复方混悬滴眼液中氯替泼诺含量及有关物质。方法: 采用HPLC法,色谱柱：Inertsil ph苯基柱（250 mm×4.6 mm,5 μm）;流动相A：0.25%醋酸溶液 乙腈（80∶20）;流动相B：乙腈;流速：2.0 ml·min^-1,进行线性梯度洗脱;检测波长：244 nm;柱温：30℃;进样量：20 μl。结果: 主成分与各杂质峰分离度良好。氯替泼诺浓度在0.001~1.02 mg·mL^-1（r=0.999 9）范围内与峰面积线性关系良好,平均回收率为99.9%,RSD为0.9%（n=9）。结论:该方法灵敏准确,色谱峰分离完全,可用于氯替泼诺妥布霉素混悬滴眼液的质量控制。     

果蝇在抗衰老药物研究中的应用

果蝇作为广泛应用于衰老研究领域的模式生物,与其他衰老的动物模型相比较,果蝇衰老模型具有生长周期短,繁殖力强,雌雄易分辨,实验操作简单的优点,能够保证足够的数量以及足够的空间进行实验,同时还有基因保守性高等特点,因此是一种常用的衰老模式生物,近些年其在加快抗衰老药物的筛选速度和衰老的机制研究等方面显示出潜在的应用价值。对果蝇衰老模型的建立方法、给药方式、药效学评价、抗衰老通路及果蝇在部分抗衰老中药中的应用5个方面进行综述,分别介绍了5种果蝇衰老模型,不同的给药方式以及行为学,生化指标和代谢组学方面的研究,分析了模式生物果蝇与衰老相关的信号通路和机制,列举了的部分抗衰老中药在衰老模式生物果蝇中的应用,为今后衰老机制的研究、抗衰老中药物和保健品的开发等提供理论依据和实验参考。     

糖皮质激素对神经元烟碱受体的调制作用(英文)

目的:研究糖皮质激素皮质酮对PC12细胞烟碱受体的非基因组作用.方法:采用全细胞膜片箝技术记录神经生长因子分化的PC12细胞上的乙酰胆碱(ACh)诱发电流(I_(ACh)).结果:PC12细胞上I_(ACh)是由烟碱受体引起的.同时给予ACh(3Oμmol/L)和皮质酮(0.1-10μmol/L)加速I_(ACh)的衰减且轻微抑制I_(ACh)峰值.用相同浓度的皮质酮预处理细胞可加强对I_(ACh)峰值的抑制率而不影响受体失敏速率.牛血清白蛋白耦联的皮质酮(0.1-10μmol/L)对I_(ACh)有类似于皮质酮的快速抑制作用.此快速抑制作用呈可逆性、浓度依赖性和非电压依赖性.结论:皮质酮可快速抑制PC12细胞I_(ACh),已是由非基因组机制介导的.皮质酮结合于膜外的特异结合位点,很可能直接作用于神经元烟碱受体,以一种非竞争方式抑制I_(ACh),从而调控交感神经元的儿茶酚胺释放.     

3种海藻多糖抗氧化及其抗衰老活性的初步研究

为探讨海藻多糖抗氧化活性及抗衰老作用,体外测定昆布多糖,羊栖菜多糖,海蒿子多糖对羟基自由基,超氧自由基及其DPPH自由基的清除作用;采用秀丽隐杆线虫为研究模型,在培养基中添加不同浓度的海藻多糖,每日定时观察并记录线虫存活数,计算平均存活率。结果表明海藻多糖具有抗氧化能力,其中1.2mg/mL的昆布多糖羟基自由基清除能力最强,达到92.10%;海蒿子多糖DPPH自由基的清除能力最强,当浓度达到1.2mg/mL时,清除率为59.55%;1mg/mL海蒿子多糖超氧自由基的清除率达15.66%。秀丽隐杆线虫寿命实验表明,不同的海藻多糖均能延长线虫的寿命,且在实验浓度下,多糖浓度越高寿命延长越明显。研究结果表明所选海藻多糖具有显著的体外抗氧化活性,动物实验表明海藻多糖具有抗衰老作用,能显著延长线虫寿命。该结果为海藻多糖应用于医药、保健品领域的开发提供了一定的实验基础。     

Spray-drying Nanocapsules in Presence of Colloidal Silica as Drying Auxiliary Agent: Formulation and Process Variables Optimization Using Experimental Designs

Purpose Spray-drying process was used for the development of dried polymeric nanocapsules. The purpose of this research was to investigate the effects of formulation and process variables on the resulting powder characteristics in order to optimize them. Materials and Methods Experimental designs were used in order to estimate the influence of formulation parameters (nanocapsules and silica concentrations) and process variables (inlet temperature, spray-flow air, feed flow rate and drying air flow rate) on spray-dried nanocapsules when using silica as drying auxiliary agent. The interactions among the formulation parameters and process variables were also studied. Responses analyzed for computing these effects and interactions were outlet temperature, moisture content, operation yield, particles size, and particulate density. Additional qualitative responses (particles morphology, powder behavior) were also considered. Results Nanocapsules and silica concentrations were the main factors influencing the yield, particulate density and particle size. In addition, they were concerned for the only significant interactions occurring among two different variables. None of the studied variables had major effect on the moisture content while the interaction between nanocapsules and silica in the feed was of first interest and determinant for both the qualitative and quantitative responses. The particles morphology depended on the feed formulation but was unaffected by the process conditions. Conclusion This study demonstrated that drying nanocapsules using silica as auxiliary agent by spray drying process enables the obtaining of dried micronic particle size. The optimization of the process and the formulation variables resulted in a considerable improvement of product yield while minimizing the moisture content.     

药物安全性研究中免疫系统的病理学评价

免疫系统是一个复杂的、涉及多个器官的系统,自身易受年龄、性别、环境等多个因素的影响,其正常的生理变异较大,因此在临床前安全性研究中评估药物所致的免疫毒性是一个巨大的挑战。目前,免疫系统的组织形态学评价是确定免疫毒性公认的基石。就免疫系统病理学评价相关的指导原则,以及胸腺、脾脏、淋巴结等重要免疫器官的病理学评价进行简要论述,以帮助毒性病理学家准确和一致性评价免疫系统中预期的或意外的药物所致的毒性改变。