坎地沙坦酯晶型含量分析方法的可行性探索

摘要：目的:建立基于X-射线粉末衍射法的坎地沙坦酯晶型Ⅲ含量的定量分析方法。方法:制备坎地沙坦酯晶型Ⅰ和晶型Ⅲ,采用X-射线粉末衍射法对两种晶型进行表征并确定其特征峰,最终选取晶型Ⅰ的特征峰(衍射角2θ为9.83°)和晶型Ⅲ的特征峰(衍射角2θ为7.28°)的峰高比值为定量参数,采用标准曲线法测定坎地沙坦酯晶型Ⅲ的含量,并进行方法学验证。结果:坎地沙坦酯晶型Ⅲ在晶型Ⅰ和晶型Ⅲ混合物中质量分数为1%～50%的范围内与其对应的峰高比值具有良好的线性关系(r=0.999 9),平均回收率为99.7%,RSD为0.12%(n=15)。结论:该方法专属性良好,准确度高,操作简单方便,适用于坎地沙坦酯原料药中晶型Ⅲ的含量测定。     

国产利福平口服制剂质量评价

目的:采用法定检验方法与探索性研究方法相结合评价国产利福平口服制剂的质量现状及存在问题。方法:按照2010年度国家评价性抽验计划总体要求,采用现行标准对抽验样品进行法定检验;建立或完善了用于探索性研究的多个方法:采用添加原料识别辅料的方法,建立了口服制剂中利福平晶型判别的粉末X-衍射法,对国内外胶囊所用原料进行测定;目测法观察胶囊内容物的颜色,考察其与晶型的关系;建立判定利福平胶囊制剂所用原料晶型的近红外定性模型;采用HPLC-UV-ESI-IT-MSn联用技术,借助MatLab分析软件,对药典色谱条件下色谱图中主要色谱峰进行结构认定,并采用SPSS软件对上述数据进行统计分析;采用斑马鱼模型对比利福平及其部分有关物质对斑马鱼胚胎发育的毒性;分别采用常压干燥、减压干燥和卡氏法测定不同处方胶囊中的水分含量。结果:法定检验:检验226批利福平口服制剂,222批合格,合格率为98.2%,4批不合格项目均为干燥失重;探索性研究:国内胶囊和片剂所用利福平原料均为I型,国外主要为Ⅱ型,部分为I型;胶囊内容物所用原料为I型的呈鲜红色,Ⅱ型的呈暗红色,与粉末X-衍射结果一致;从有关物质检出的类型、个数和检出量结果显示,国产利福...     

粉末X-射线衍射技术定量测定注射用美罗培南中美罗培南晶型I的含量

目的 采用粉末X-射线衍射技术（powder X-ray diffraction,PXRD）对三家公司的注射用美罗培南制剂中美罗培南晶型I进行定量分析和对比。方法 采用粉末X-射线衍射精细扫描方法,选择2θ=12.9°特征衍射峰强度经被试验样品质量校正后作为定量参数,建立标准曲线,测定三家公司的注射用美罗培南中美罗培南晶型I的含量,并与高效液相方法测定制剂中美罗培南的总含量进行比较。结果 在美罗培南晶型I含量为5%～120%的范围内,得到的标准曲线为Y=553.8X-105.9(r=0.998 4）;三家公司制剂中晶型I含量均略低于美罗培南总含量。结论 建立方法操作简单快捷,能够在辅料没有干扰的情况下用于注射用美罗培南中美罗培南晶型I的含量分析,可为美罗培南的质量控制和晶型稳定性研究提供参考。     

替勃龙Ⅰ晶型定量分析标准曲线的建立

目的 替勃龙(tibolone)工业生产过程中需对产品进行定量分析,以确定目标晶型的含量.方法 本文采用X射线粉末衍射(PXRD)技术建立了用于Ⅰ晶型定量分析的标准曲线.进行X射线粉末衍射前,需对样品进行研磨.由于研磨将导致替勃龙晶体的晶型发生转变,因此本试验利用X射线粉末衍射法与差式量热扫描法(DSC)对玛瑙研钵、陶瓷研钵两种研磨材料进行了考察.结果 确定了最佳研磨方式与研磨时间,即陶瓷研钵研磨2min.并运用该方法进行制样,进行X射线粉末衍射.最终得到的标准曲线方程为Y=322.52X-206.54; X为特征峰强度比,Y为Ⅰ晶型的质量分数,相关系数R2=0.9994.运用标准曲线对已知质量分数的样品进行定量分析,确定检测下限为10％,对于Ⅰ晶型质量分数大于10％的样品,结果表明其相对误差均小于2％.结论 建立的标准曲线可用于较高精度的物相定量分析,为替勃龙产品的晶型比例分析提供了有效的方法.     

拉曼光谱法检测拉米夫定晶型Ⅰ

以红外光谱、X射线粉末衍射和拉曼光谱表征拉米夫定的晶型Ⅰ和晶型Ⅱ.选用拉曼光谱分析技术,以拉米夫定晶型I的特征峰(697 cm-1)与内标峰(537 cm-1)的强度比为定量参数,测定拉米夫定中晶型Ⅰ的含量.拉米夫定晶型Ⅰ的特征峰与内标峰的强度比在晶型Ⅰ浓度0～ 100％范围内线性关系良好,最低检测限为1.2％,最低定量限为3.7％.     

氟康唑的多晶型及转化研究

目的对氟康唑的多晶型及其相互转化进行分析研究。方法采用红外光谱仪(IR)、近红外光谱仪(NIR)、拉曼光谱仪(RM)、X-射线粉末衍射仪(XRD)、差示扫描量热仪(DSC)和热重分析仪(TGA)对氟康唑的晶型进行了研究,并考察了温度、湿度、溶剂和研磨对其晶型转化的影响。结果 X-射线粉末衍射法作为晶型判定方法,10个厂家18批氟康唑的晶型有Ⅱ型、Ⅲ型和一水合物晶型;在不同的温度、湿度和结晶溶剂中Ⅱ型和一水合物晶型可相互转化,在氯仿中结晶和高温熔融可得到I型结晶。结论氟康唑不同晶型谱学特征显著,可对氟康唑晶型进行质量控制,各晶型间可以相互转化并确定了转化条件。     

马来酸替加色罗的晶型研究

目的：研究马来酸替加色罗2种晶型的物理性质。方法：运用傅立叶变换红外光谱、拉曼光谱、热分析和粉末X-射线衍射法研究马来酸替加色罗的晶型。结果：运用不同的重结晶溶剂，马来酸替加色罗可形成2种晶型，这2种晶型的熔点一致，它们的DSC和TG曲线都相同。但他们的红外光谱、拉曼光谱和粉末X-射线衍射图谱均存在着差异。结论：红外光谱、拉曼光谱和粉末X-射线衍射图谱可作为鉴别马来酸替加色罗晶型的方法。     

道地产区湖北应城石膏X-射线衍射专属特征峰的分析研究

摘 要 目的： 确定道地产区湖北应城石膏X-射线衍射专属特征峰。 方法: 应用X-射线衍射方法,对不同产地中药石膏进行指纹图谱分析,确定共有峰;并对道地产区湖北应城石膏的特征峰进行专属性鉴别。结果:获得不同产地石膏X-射线衍射指纹图谱,确定16个平均值共有峰;道地产区湖北应城产淡黄色纤维状石膏,其X-射线衍射图谱中具有两个专属特征峰,晶面间距（d）分别为1.68与1.51。 结论: 道地产区湖北应城石膏X-射线衍射专属特征峰的确定,可区别其他产地石膏,为进一步评价中药石膏的品质提供依据。     

四种利福定结晶的特性研究

对利福定四种结晶产品进行了结晶特性的描述,并讨论了它们的热分析谱(TG、DTA、DSC)、红外光谱、粉末X-射线衍射谱以及热显微镜观察结果。Ⅳ型晶室温长期留样或硅胶干燥再吸湿可转化成Ⅰ型晶。研磨可使Ⅰ、Ⅲ、Ⅳ型晶体成无定形。本文为利福定产品的晶型鉴识提供了特征依据。     

花蕊石及其炮制品的粉晶X射线衍射分析

目的 建立花蕊石及其炮制品的粉晶X-射线衍射分析方法,评价该方法区分花蕊石及其他含钙矿物药的应用价值.方法 应用粉晶X-射线衍射法对11批生花蕊石和8批煅花蕊石药材进行定性分析,并用MDI Jade5.0软件比较其共有峰的夹角余弦和相关系数的相似度.结果 不同来源的花蕊石样品粉晶X-衍射图谱共有峰相似度,生花蕊石:74%～99%,煅花蕊石:99%以上,与其他矿物药区别明显.结论 煅花蕊石的粉晶X-衍射分析方法专属性强,准确,可作为与其他矿物药进行区分鉴别的手段.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Glycofection: The Ubiquitous Roles of Sugar Bound on Glycoplexes

Glycofection (transfection by using sugar-substituted polylysine) was assessed in order to provide an alternative to viral vectors for the transfer of genes into vascular smooth muscle cells. A rabbit vascular smooth muscle cell line (Rb-1 cells) was selectively transfected by using glycoplexes (glycosylated polylysine/pSV2LUC complexes) in the presence of 10 mu M of the fusogenic peptide GALA. A sugar-specific transfection was obtained when the glycofection was conducted for 1 h with glycoplexes containing either alpha Gal, alpha -Glc, alpha -GalNAc, beta -GlcNAc, or beta -GalNAc residues. The gene expression was high after transfection, with glycoplexes bearing alpha Gal, alpha -GalNAc, or beta -GalNAc residues that were weakly internalized, and low with glycoplexes carrying Lact or Rha residues that were well taken up by cells. These results suggest that 1) glycofection can be a good approach for a selective transfer of genes intovascular smooth muscle cells, 2) an efficient uptake of the glycoplexes is not the unique limiting step for an efficient transfection, and 3) the sugar-dependent trafficking of the glycoplexes inside the cells may account for the transfection efficiency.     

直肠癌下切缘病理组织学分析

目的探讨直肠癌逆向浸润与下切缘的安全距离的关系。方法对36例直肠癌Miles手术和Dixon手术后标本的肿瘤下缘1.0cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查,观察直肠癌逆向浸润或转移的距离。结果36例直肠癌标本距癌肿下缘1.0 cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查均为阴性,结论直肠癌远恻逆向浸润或转移未见超过1.0cm,因此认为保肛手术时切除肿瘤远侧肠管(包括系膜)2.0cm是安全的。