硫酸氢钠催化合成硝基卡因

采用硫酸氩钠为催化剂,以对硝基苯甲酸和N,N-二乙基乙醇胺为原料,直接酯化合成了硝基卡因。研究表明,硫酸氢钠是合成硝基卡因的良好催化剂。合成硝基卡因的最佳工艺条件为:醇酸比为1:1(摩尔比),催化剂的用量为对硝基苯甲酸的6%(质量分数),在回流温度下反应14h,产率达到79.5%。比没有催化剂反应14h的产率(72.4%)提高9.8%。     

固体酸(TiO2/Fe3+)催化对硝基苯甲酸乙酯合成的研究

目的以TiO₂/Fe³⁺催化合成对硝基苯甲酸乙酯。方法用TiO₂/Fe³⁺催化合成对硝基苯甲酸乙酯,产品通过MS检测,并用正交试验确定了其最佳反应条件。结果最佳反应条件为:酸醇摩尔比为1∶6,反应温度为90℃,反应时间为2h,收率达88%。结论该法能顺利实现对硝基苯甲酸和乙醇的酯化。     

正交实验设计优化光敏剂紫红素-18的合成工艺

目的优化光敏剂紫红素-18（1）的合成工艺。方法以脱镁叶绿酸a（2）为原料,经空气氧化及碱开环制得化合物1;选择影响其合成产率的反应时间（A）、氢氧化钾溶液浓度（B）、反应溶剂（C）和化合物2与氢氧化钾的质量投料比（D）为考察因素,每个因素各取三个水平,采用L9（34）正交试验法优化目标物1的最佳合成工艺。结果合成目标物1的最优反应条件为B1C2A2D2,反应工艺收率从34.4%提高到45.6%。结论新工艺提高了收率、缩短了反应时间、消除了毒性溶剂,适合工业化生产     

取代咪唑酮合成工艺研究

目的:优化取代咪唑酮类化合物的合成工艺.方法:采用正交设计法,重点考察反应溶剂,投料比例及温度对收率的影响.结果:投料比例对收率的影响最为显著.结论:使收率由低于10%提高到42.5%,使得更加符合工业生产的要求.     

亚氨基二乙酸及其双乙酯的合成研究

目的主要研究一步法合成亚氨基二乙酸二乙酯以及催化剂的用量、醇酸摩尔比、反应时间等因素对酯化反应的影响.方法通过氯乙酸法和脱氢氧化法分别合成了亚氨基二乙酸,采用十二水合硫酸铁胺催化直接酯化法合成亚氨基二乙酸二乙酯,并通过正交实验优化酯化反应条件.结果十二水合硫酸铁胺催化合成亚氨基二乙酸二乙酯,酯化反应适宜条件是催化剂2 g/1 mol酸,mol酸∶mol醇=1∶8,反应时间是3 h,转化率在85.0%以上.结论十二水合硫酸铁胺催化合成亚氨基二乙酸二乙酯,催化剂活性高,反应温和,操作简单,收率优良.     

正交设计法优化硝酸益康唑的合成工艺

目的:优化抗真菌药物硝酸益康唑的合成工艺。方法:采用正交设计法,重点考察反应温度、催化剂、反应时间及溶剂四个因素对收率的影响。结果:溶剂对反应收率的影响最为显著,其次是反应时间和催化剂。结论:新工艺原料价廉易得,反应条件温和,后处理简便,收率高。     

正交设计优化光敏剂二氢卟吩e6-C15单甲酯的合成工艺

目的优化光敏剂二氢卟吩e6-C15单甲酯(1)的合成工艺。方法采用"一锅法",以脱镁叶绿酸a(3)为原料,通N2条件下经碱甲醇液作用下E环开裂后直接添加1/20体积量的水,回流水解制得化合物1。选择影响其合成产率的开环反应时间(A)、回流水解反应时间(B)、氢氧化钾甲醇液浓度(C)、3与氢氧化钾的质量投料比(D)为主要考察因素,每个因素各取3个水平,采用L9(34)正交试验法优化目标物1的最佳合成工艺。结果合成化合物1的最优反应条件为B1C2A2D1,工艺收率从43.0%提高到56.5%。结论该工艺具有操作简便、安全、收率高等优点,适合工业化生产。     

牛磺酸镁盐制备工艺的改进

目的研究牛磺酸镁盐的制备工艺,以提高产物收率。方法以酸碱中和反应合成牛磺酸镁盐,采用正交试验对制备工艺进行优选。结果改进后最佳工艺条件:反应温度80℃;反应时间5h;牛磺酸与氢氧化镁投料摩尔比2∶1(氢氧化镁略过量)。结论该工艺合理,操作简便,收率可达55%。     

葡萄糖酸镁合成工艺研究

目的 :研究葡萄糖酸镁的化学合成方法。方法 :以葡萄糖酸内酯和氧化镁为原料 ,采用正交设计方法优化出葡萄糖酸镁最佳合成工艺。结果 :最佳合成条件 :葡萄糖酸内酯∶氧化镁投料 (摩尔比 )为1∶0 6 ;反应温度为100℃ ;反应时间为3h ,总收率为95 %以上。结论 :该合成方法收率稳定 ,合成周期短 ,合成线路完全可行     

青霉素G钾催化氧化制备青霉素G亚砜的研究

目的 研究青霉素G钾制备青霉素G亚砜的工艺。方法 采用偶氮二甲酸二乙酯(DEAD)-30％H2O2组成的催化氧化体系。结果 通过正交实验确定了最佳反应条件为：反应温度0-5℃，投料比1：1.5，双氧水浓度为30%，青霉素G钾与DEAD的摩尔比为1：0．5，溶剂采用水 相转移催化剂，收率为40.0%。结论 产物的红外图谱与青霉素G亚砜标准品一致，收率低于过氧乙酸氧化法，但不产生含酸废水。     

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.     

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.     

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.