注射用清开灵（冻干）质量控制进展研究

摘要：目的 综述注射用清开灵（冻干）国内外研究进展。方法 查阅关于清开灵有关的文献资料,依据“中药注射剂指纹图谱研究的技术要求（暂行）”和《中国药典》2015年版相关要求规定。结果 通过查阅文献,对清开灵的研究现状、指纹图谱、含量测定及重金属测定进行归纳总结。结论 为注射用清开灵（冻干）的质量标准提升研究提供参考依据。     

基于超高效液相色谱的清开灵注射液多指标成分定量指纹图谱研究

本研究在清开灵注射液高效液相色谱指纹图谱分析方法基础上,基于超高效液相色谱,建立清开灵注射液多波长多指标成分定量指纹图谱分析方法。遵循Lc/dp(色谱柱柱长/填料粒径)相近以获取与HPLC相近的柱效和分离效果的原则选择色谱柱,并以分离度、理论塔板数和拖尾因子等系统适用性参数为指标,优化调整流速、柱温、进样体积、梯度时间、梯度陡度和采样频率等色谱条件,同时测定了清开灵注射液中尿苷、鸟苷、腺苷、色氨酸、绿原酸、栀子苷、京尼平龙胆二糖苷和咖啡酸等成分含量。实验结果表明,经方法转换建立的清开灵注射液超高效液相色谱分析方法可用于其化学成分的全息定量表征,方法快速、准确、灵敏度高。本研究为其他中药复杂物质体系HPLC和UHPLC分析条件相互转换提供理论和实验依据。     

HPLC/ELSD指纹图谱和星座图聚类法在清开灵注射液质量评价中的应用

目的对清开灵注射液的质量进行科学评价，为有效控制中药质量提供一种可靠方法。方法采用HPLC/ELSD指纹图谱技术结合星座图聚类法，测定不同厂家的18个批次清开灵注射液的指纹图谱，并评价产品质量。结果本法直观、准确地表达了产品的质量信息。结论本法是中药质量评价的一种直观、合理、有效的技术手段。     

进口血竭药材与国产血竭指纹图谱的比较研究

目的研究比较进口血竭药材与国产血竭药材的指纹图谱。为血竭药材质量控制提供有效的方法。方法利用HPLC指纹图谱技术研究、比较两者之间指纹图谱差别。结果测定了6批国产血竭及1批进口血竭的指纹图谱,两者指纹图谱差别明显。结论建立HPLC法测定血竭药材的指纹图谱,为血竭药材质量控制提供依据。     

色谱指纹图谱在中药注射剂中的应用进展

自国家药品监督管理局2000年颁布<中药注射剂指纹图谱研究的技术要求(暂行)>以来,中药注射剂指纹图谱的研究日益受到人们的重视.本文重点对指纹图谱的分类和中药注射剂色谱指纹图谱技术进展进行了综述,并对色谱指纹图谱在中药注射剂中的应用进行了展望.     

浅谈中药指纹图谱技术的发展现状

中药指纹图谱(TCM fingerprinting)研究作为新的中药质量控制的手段,是伴随中国传统医药产业化,现代化和全球化而提出的。它是借助于波谱或色谱技术获得的中药(主要是植物药)次生代谢化学成分的光谱图或色谱图,是一种综合的、可量化的鉴别手段,用于鉴别中药材的真伪。其基本特征是整体性和模糊性,应满足专属性、重现性和实用性的技术要求。1中药指纹图谱的概述1．1中药指纹图谱的起源与发展指纹(fingerprint)概念来源于法医学,依据每个人的指纹结构上微小差别可以鉴别区分不同的人。近代指纹分析的概念结合生物技术的发展延伸到了DNA指纹图谱分析,而且应用范围也从犯罪学扩大到医学和其他生命科学领域。中药指纹图谱借用法医学中指纹具有“绝对唯一性(absolute uniqueness)”的特点而得名,是在中药化学成分色谱指纹图谱的基础上发展而来的。中药指纹图谱不仅是一种中药质量     

白芷有效成分含量测定及其指纹图谱研究

目的研究白芷有效成分含量测定及其指纹图谱情况。方法选取2012年5月我院购进的白芷21批,以数字法随机分为观察组(10例)和对照组(11例)。采用高效液相色谱法对其进行成分含量的测定,同时对21批白芷进行指纹图谱的测定确定21个峰为共有特征色谱峰,并建立白芷药材HPLC指纹图谱,对白芷质量进行测量与判定。结果指纹图谱对白芷检测的结果较为精准,具有积极意义。两个组别共有指纹峰相对保留时间的RSD以及相对峰面积的RSD两组对比没有显著差异,表明指纹图谱检测具有见较高的重复性以及稳定性。结论白芷指纹图谱建立,能快速、准确地鉴定白芷药材质量以及有效成分含量。     

高乌头炮制品的HPLC指纹图谱研究及其2种生物碱成分含量测定

目的 建立不同产区高乌头炮制品的HPLC指纹图谱,并测定2种生物碱成分的含量,为高乌头制品质量控制提供参考依据。方法 通过HPLC梯度洗脱建立高乌头炮制品的指纹图谱,并采用中药指纹图谱相似度评价系统(2012版)、主成分分析(PCA)和聚类分析(CA)对指纹图谱进行分析。结果 建立了高乌头炮制品指纹图谱,10批高乌头制品的相似度均大于0.90,标定共有峰18个,并对其中2主要成分(高乌甲素、冉乌头碱)进行含量测定;聚类分析(CA)将所有批次高乌头制品分为4类,反映了10批不同产区高乌头制品的质量特征;主成分分析(PCA)筛选出累计贡献率达到88.824%的4个主成分,得到决定高乌头药材质量7个化学成分。结论 该方法重现性好、特征性强可用于高乌头炮制品全面质量评价。     

岩黄连注射液与药材及其提取物间指纹图谱相关性研究

目的:研究岩黄连注射液、岩黄连药材及其提取物指纹图谱的相关性,为建立岩黄连注射液指纹图谱的检测标准提供依据。方法:采用 HPLC 法,Shim-pack CLC-ODS 色谱柱(250mm×6.0mm,5μm),乙腈-缓冲溶液[0.05moL·L~(-1)庚烷磺酸钠-0.05moL·L~(-1)磷酸二氢钾(1:1),含0.2%乙二胺,用磷酸调 pH 3.0]梯度洗脱,流速为1mL·min~(-1),检测波长285nm。以中药色谱指纹图谱相似度评价系统的操作规范(版本2004A)计算。结果:岩黄连注射液与药材及其提取物间指纹图谱均有较好的相关性。结论:本研究为岩黄连注射液指纹图谱的制订提供依据。     

不同产地斑蝥超微粉体的HPLC指纹图谱及斑蝥素的含量测定

目的:结合斑蝥主要成分斑蝥素的含量测定与指纹图谱,比较不同产地药材化学成分的差异性,为科学评价不同产地斑蝥药材及其超微粉体的质量提供依据。方法:建立斑蝥超微粉体指纹图谱检测方法。采用高效液相色谱(HPLC)法对各产地斑蝥超微粉体进行分析,采用中药色谱指纹图谱相似度评价系统软件比较指纹图谱的相似度,采用SPSS 13.0统计软件对10批样品进行聚类分析,并测定斑蝥素含量。结果:不同产地斑蝥超微粉体指纹图谱有较大相似性,但斑蝥素的含量有一定的差异。聚类分析结果表明,不同产地斑蝥药材存在一定差异,但差别不大。结论:所建立的HPLC指纹图谱具有较好的精密度、重复性和稳定性,结合斑蝥素的含量,可为斑蝥药材及其超微粉体质量评价提供依据。     

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.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

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.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

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.