RP-HPLC测定利普司他汀的含量

目的建立奥利司他中间体利普司他汀发酵效价的RP—HPLC内标检测法。方法采用ODS色谱柱（4．6mm×250mm，3μm），以83％乙腈-水溶液为流动相，以奥利司他为内标物，进样量10止，检测波长为195nm。结果在0．0～1．0mg／mL范围内，利普司他汀浓度与峰面积线性关系良好（r=0．9992）。结论本方法可准确检测发酵液中利普司他汀效价。     

RP-HPLC法检测发酵液中利普司他汀的效价

目的建立奥利司他中间体利普司他汀发酵效价的检测方法。方法采用RP-HPLC法。色谱柱为Ultimate ODS硅胶柱(4.6 mm×250 mm,5μm),流动相为乙腈-水(体积比4∶1),柱温为35℃,进样量为10μL,流速为1.1 mL·min-1,检测波长为210 nm。结果发酵70、100和130 h时测得发酵液中利普司他汀效价分别为2.518、4.323、6.981 g·L-1。结论该方法可有效地检测发酵液中利普司他汀效价。     

抗生素链霉菌合成喷司他汀发酵工艺的关键原料研究

目的 通过抗生素链霉菌对发酵培养基和发酵工艺优化,对发酵过程中所用的关键原料进行了研究,提高喷司他汀的发酵产量。方法 考察和评估抗生素链霉菌发酵生产喷司他汀发酵培养基中的关键原料,研究关键材料的供应商及用量,提高喷司他汀产量,于5000L发酵罐上进行发酵工艺验证试验。结果 喷司他汀摇瓶发酵单位达232mg/L,结果较原始工艺提高了28%;在5000L发酵罐发酵单位达210mg/L,较原始工艺提高了74%。 结论 控制发酵培养基中的植物油种类、来源和用量,能有效提高喷司他汀的生物合成。     

螺旋霉素发酵滤液反萃取过程工艺研究

研究了螺旋霉素发酵滤液提取过程中反萃取工艺特性，考察了酸度，温度和酸水体系等诸因素对反萃取过程和反萃取分离系数的影响。实验发现，反萃取过程中有最佳酸度和温度范围，分别在ＰＨ３．５左右和１５－２５℃。     

螺旋霉素发酵液萃取过程工艺研究

研究了螺旋霉素发酵滤液提取过程中的萃取工艺特性，考察了温度、酸度等诸因素对萃取过程和萃取分配系数α的影响。实验发现，萃取过程中的最佳酸度范围在ｐＨ９～１０左右，而且温度影响其分配系数α。在此基础上推导并建立了Ｔ＝５～３５℃，ｐＨ７～１０时萃取分配系数数学模型：α＝７３．５６ｅｘｐ［－ΔＨｍＲ（１Ｔ－１Ｔ０）］／（１＋１０８．４－ｐＨ＋１０１５．５－２ｐＨ）     

葡萄籽中原花青素的超临界CO2萃取工艺优选

目的：探讨超临界CO2流体萃取葡萄籽中原花青素的方法，选出最佳的提取工艺参数。方法：以原花青素含量为指标，考察了萃取温度、压力、CO2流量、萃取时间4个因素对葡萄籽中原花青素的超临界CO2流体萃取的影响。结果：以甲醇做夹带剂，药材质量30g，萃取压力32MPa，萃取温度40℃，CO2流量为10L·h^-1的条件下萃取60min为最佳工艺。结论：超临界CO2萃取法提取葡萄籽中原花青素耗时少、准确、效率高。     

超临界CO2提取香附、当归挥发油的工艺研究

目的确定舒经克痛软胶囊中挥发油成分的提取路线并优化工艺参数。方法采用超临界CO2萃取法，使用正交试验设计方案，以提取率为指标，对萃取温度、萃取压力、分离压力和分离温度等影响因素进行考察。结果萃取压力、分离压力、分离温度对提取率的影响具有显著性意义，萃取温度无显著性意义。采用超临界CO2萃取法萃取舒经克痛软胶囊中挥发油成分的最佳工艺条件为：香附：萃取压力15mPa、萃取温度45℃、分离压力10mPa、分离温度30℃；当归：萃取压力25mPa、萃取温度50℃、分离压力8mPa、分离温度40℃。结论该方法简便，可靠，选择性高，适工业化生产。     

超声法提取黄连中紫外吸收剂的试验研究

目的：研究超声提取法提取黄连中天然紫外吸收剂的优化工艺。方法：用分光光度法测定所提取紫外吸收剂的含量，考察了超声时间、乙醇浓度、料液比、超声温度以及萃取次数对黄连萃取液吸光度的影响。结果：较佳工艺为50％乙醇水溶液为萃取剂，料液比1：25（g/ml），在50℃超声提取50min，萃取一次。结论：超声提取法用于黄连中紫外吸收剂的提取是一种简单、快捷、高效的提取方法。     

均匀设计法优选莪术挥发油提取工艺的研究

目的优选莪术挥发油的超临界CO2提取工艺条件。方法以莪术挥发油提取率为指标,采用均匀设计法,考察萃取压力、萃取时间、解析压力和解析温度对提取率的影响。结果优选提取工艺最佳条件为:萃取压力23.5MPa,萃取温度45℃,解析压力7.5 MPa,解析温度50℃。结论本萃取工艺条件简便、效率高。     

超临界CO_2萃取烈香杜鹃挥发油的工艺研究

目的研究超临界CO2萃取烈香杜鹃挥发油的最佳工艺。方法以挥发油的提取量为评价指标,选择萃取压力、萃取温度、萃取时间为考察因素,采用L9(34)正交实验方法,对超临界CO2萃取烈香杜鹃挥发油的工艺进行考察。结果最佳提取工艺为萃取压力20mPa,萃取温度45℃,萃取时间1.5h。结论该工艺的提取率高,稳定性好,为规模化生产提供了依据。     

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.     

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.