披针叶黄华地上部分金雀花碱的分离纯化工艺研究

目的研究采用树脂从披针叶黄华地上部分中分离纯化金雀花碱的工艺条件。方法以金雀花碱为目标成分,以N-甲酰基金雀花碱为杂质的指标成分,对多种树脂材料的纯化效果进行筛选,并对影响分离纯化效果的主要因素,如上样液pH值、浓度及洗脱剂组成等进行优化。结果以氢型001×7型阳离子交换树脂为纯化载体,调节披针叶黄华地上部分提取液pH至12左右上样后,再以1.0 mol·L-1氨水-体积分数为90%的乙醇洗脱,可有效去除部分生物碱杂质成分,提取物中金雀花碱质量分数最高达到44.61%,纯化倍数达到6倍以上,N-甲酰基金雀花碱的去除率最低为89.75%。结论提供了一种从披针叶黄华地上部分高效分离纯化金雀花碱的方法。     

延胡索总生物碱提取工艺的实验研究

目的:筛选延胡索总生物碱的最佳提取工艺。方法:按正交试验表提取,利用生物碱易溶于酸水难溶于碱水的特点对提取物纯化,采用紫外分光光度法测定总生物碱含量,以延胡索总生物碱含量及干膏率为检测指标,确定最佳提取工艺。结果:最佳提取工艺为:8倍量60%乙醇,提取3次,2h/次。结论:该工艺提取率高,稳定性好,为延胡索总生物碱的进一步药理作用研究提供参考。     

复方两面针镇痛软膏药材浸提工艺优化

目的：探索复方两面针镇痛软膏药材提取的最佳工艺条件。方法：以总生物碱浸出收率为指标,考察浸提乙醇浓度、倍量、浸提时间、浸提温度、浸提次数对干浸膏得率和总生物碱含量的影响。通过单因素试验和正交试验,得出浸提最佳条件。结论：影响药材浸提收率的因素主次顺序依次为：浸提温度＞乙醇倍量＞浸提次数＞浸提时间＞乙醇浓度。     

正交试验优选云南萝芙木中总生物碱的提取工艺

目的:优选云南萝芙木中总生物碱的最佳提取工艺。方法:采用L16(45)正交设计,以浸膏得率、总生物碱的含量为指标,以提取溶剂浓度、加热时间、料液比、提取次数、提取温度为因素,优化云南萝芙木中总生物碱的提取工艺。结果:最佳提取工艺为75%乙醇,加热3h,料液比为1∶10,加热4次,加热温度为70℃。在最佳工艺条件下,总生物碱含量为1.24%。结论:优选得到的提取工艺简单、稳定、可行。     

混合均匀试验优选飞龙掌血散剂总生物碱提取工艺

目的:优选飞龙掌血散剂中总生物碱的提取工艺,并建立总生物碱含量测定方法。方法:以加水量、提取时间和提取次数为考察因素,以总生物碱含量为评价指标,采用混合均匀试验优选提取工艺,并采用酸性染料比色法测定总生物碱含量。结果:最佳提取工艺为加入12倍量水,提取2次,每次90min,该工艺下总生物碱含量为1.53%。结论:所选工艺和含量测定方法合理、可行,可为飞龙掌血的进一步研究提供参考。     

草乌花及其煎煮液中二萜生物碱的电喷雾串联质谱研究

目的对草乌花及其煎煮液中的二萜生物碱进行定性分析,说明煎煮前后化学成分发生的变化. 方法用注射泵自动进样,电喷雾离子阱串联质谱直接分析草乌花及其煎煮液中生物碱混合物.结果在生草乌花中发现3个新生物碱,草乌花煎煮后其中的双酯型生物碱和三酯型生物碱都发生水解,前者水解为苯甲酰乌头原碱和乌头原碱类生物碱,后者水解为3-乙酰-乌头原碱类生物碱.结论该法简便、快速、灵敏、特异性强,为乌头属植物煎煮液中的生物碱分析提供了新途径.     

星点设计-响应面法优化川芎生物碱提取工艺

目的优选川芎总生物碱的提取工艺。方法对川芎采用乙醇回流提取的方法,进行星点设计,以乙醇浓度、醇倍数、提取时间为自变量,以川芎中总生物碱含量为因变量,通过对自变量各水平的多元线性回归及二项式拟合,用响应面法优选出最佳提取工艺,同时进行预测分析。结果确定了最佳提取工艺为用8倍90%的乙醇提取2次,每次2 h,提取的川芎总生物碱含量为0.693 mg.g^-1,二项式拟合复相关系数R^2=0.957 3。结论星点设计-响应面法优选川芎中总生物碱的提取工艺,方法简单,精密度高,可预测性好。     

离子液体-微波辅助提取钩藤中生物碱的工艺研究

目的优选钩藤中生物碱的提取工艺条件,制定出最佳提取工艺方案。方法采用离子液体-微波法提取,以4种代表生物碱(钩藤碱、异钩藤碱、去氢钩藤碱和异去氢钩藤碱)含量作为指标,通过单因素实验考察离子液体浓度、液料比、提取时间和pH值4个因素对提取率的影响,并通过均匀设计法优选最佳提取工艺参数。实验中用高效液相色谱法测定钩藤4种代表生物碱的含量。结果钩藤中生物碱的最佳提取条件为:选用0.54 mol.L-1离子液体[C4MIM]BF4的水溶液为提取溶剂,pH值调至1.42,液料比100∶1 mL.g-1,提取时间8 min。钩藤中4种代表生物碱的质量分数达2.52 mg.g-1。结论该提取工艺操作简便合理,重复性良好,具有可行性。     

黄柏总生物碱提取工艺的优化研究

目的研究黄柏总生物碱的最佳提取工艺。方法以酸性染料比色法测定总生物碱含量,采用正交表L9(34)考察乙醇浓度、物料比、提取时间、提取次数4个因素对其影响。结果最佳工艺为:16倍量的70%乙醇,提取3次,每次60min。结论本工艺测定方法可行,为大批量黄柏提取生物碱提供了理论依据。     

精制益母草生物碱提取纯化工艺研究

目的:优选精制益母草生物碱的提取纯化工艺。方法:采用平行设计法,以总生物碱提取量为判断指标,分别观察超声、回流、浸渍法提取益母草中生物碱的提取率,确定最佳提取工艺;以生物碱含量为判断指标,采用4种不同化学特性的ADS树脂,分别观察其在提取液不同pH环境、不同洗脱条件下,回收生物碱的量和纯度,确定最佳纯化工艺。结果:超声结合不同溶剂提取对精制益母草生物碱提取率的影响不同,以0.05%盐酸乙醇的提取干膏生物碱含量和提取率最高,平均生物碱提取率为0.373%;在回流法中,以0.05%盐酸乙醇的提取干膏生物碱含量和提取率最高,平均生物碱提取率为0.317%;在浸渍法中,以1%盐酸的提取干膏生物碱含量和提取率最高,平均生物碱提取率为0.410%。在纯化工艺方面,在提取液pH为6～8之间时,4种ADS大孔树脂对生物碱均有吸附作用,其中pH为8时ADS-B的静态吸附最强。结论:本研究建立了高效、稳定的精制益母草生物碱的提取和纯化工艺,可为进一步开发新型具有抗心肌缺血或心血管保护作用的新药奠定基础。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.