甲磺酸帕珠沙星的合成工艺改进

目的改进甲磺酸帕珠沙星的合成工艺.方法以(S)-9,10-二氟-3-甲基-7-氧-2,3-二氢-7H-吡啶[1,2,3-de][1,4]苯并噁嗪-6-羧酸乙酯为起始原料,经亲核取代、酯水解及选择性脱羧、环合、水解、霍夫曼降解、成盐得甲磺酸帕珠沙星.结果与结论合成甲磺酸帕珠沙星的化学结构经元素分析、IR、1H-NMR、MS得以确证.该工艺路线缩短了反应步骤,总收率达51.6%,适合工业化生产.     

甲磺酸帕珠沙星的合成

[目的]研究氟喹诺酮类抗菌剂甲磺酸帕珠沙星的合成路线及工艺。[方法]以左旋氧氟沙星的中间体（S）-9，10-二氟-3-甲基-2，3-二氢-7-氧-7H-吡啶[1，2，3-de]-[1,4]苯并恶嗪-6-羧酸乙酯为起始原料，经亲核取代反应，酯水解并选择性脱羧，环合，水解，Hofmann降解，成盐得甲磺酸帕珠沙星，总收率42.7%。[结果]合成了目标化合物，其化学结构经元素分析，IR，^1HNMR,^13CNMR,MS得以确正。[结论]该合成路线及工艺适合工业化大生产。     

甲磺酸帕珠沙星治疗泌尿系感染的临床观察

目的评价国产甲磺酸帕珠沙星注射液治疗泌尿系感染的临床疗效与安全性。方法下尿路感染者予甲磺酸帕珠沙星注射液0．3 g/100 mL,2次/d静点,疗程3-5 d;急性肾盂肾炎者予甲磺酸帕珠沙星注射液0．3 g/100 mL,2次/d静点,疗程7-10 d;慢性肾盂肾炎予甲磺酸帕珠沙星注射液0．3 g/100 mL,2次/d静点, 疗程10-14 d。结果痊愈率为80％,总有效率为97．78％,细菌清除率为95．56％,不良反应发生率为3％。结论甲磺酸帕珠沙星治疗泌尿系感染疗效确切,且安全性较好。     

甲磺酸帕珠沙星原料及注射剂中有关物质的定性研究

摘 要 目的：对甲磺酸帕珠沙星原料及注射剂中主要有关物质进行定性研究。 方法: 采用LC PDA MS/MS、UPLC TOF MS及核磁共振仪（1H NMR）对甲磺酸帕珠沙星原料及注射剂中主要杂质Ⅰ和Ⅱ进行结构解析与确证。 结果: 对甲磺酸帕珠沙星原料及注射剂中检出的2个主要杂质Ⅰ和Ⅱ进行了结构确证,并对其进行了溯源,确定其为原料药合成副产物。 结论: 本研究推断杂质Ⅰ和Ⅱ分别为甲磺酸帕珠沙星甲酯和甲磺酸帕珠沙星乙酯,为甲磺酸帕珠沙星原料及其注射剂工艺和质量控制提供参考。     

甲磺酸帕珠沙星治疗细菌性感染的多中心临床试验

目的：评价国产新药注射用甲磺酸帕珠沙星治疗细菌性感染的临床安全性和有效性。方法：以盐酸左氧氟沙星为对照药，进行多中心随机双盲对照治疗细菌感染的试验。试验组130例，给予注射用甲磺酸帕珠沙星300mg静脉滴注，q12h；对照组128例给予注射用盐酸左氧氟沙星200mg静脉滴注，q12h。两药疗程均为7～10d。结果：甲磺酸帕珠沙星和左氧氟沙星治疗细菌性感染的临床有效率分别为86．3％和79．7％；细菌清除率分别为89．1％和81．7％；不良反应发生率分别为6．9％和11．7％。以上指标差异均无显著性（P〉0．05）。结论：注射用甲磺酸帕珠沙星治疗细菌性感染是有效和安全的，与左氧氟沙星相当。     

甲磺酸帕珠沙星治疗非淋菌性宫颈炎合并盆腔炎疗效分析

目的：对甲磺酸帕珠沙星应用于非淋菌性宫颈炎合并盆腔炎的临床疗效进行分析。方法：选取本院收治已确诊为非淋菌性宫颈炎合并盆腔炎的患者60例，给予甲磺酸帕珠沙星进行治疗，观察治疗前后的临床症状和各项体征，并进行病原体的检测。结果：甲磺酸帕珠沙星治疗非淋菌性宫颈炎合并盆腔炎的总有效率为91.67％。结论：甲磺酸帕珠沙星能够有效治疗非淋菌性宫颈炎合并盆腔炎，清除病原体。     

甲磺酸帕珠沙星预防前列腺增生术后感染126例疗效观察

目的：观察甲磺酸帕珠沙星预防前列腺增生术后感染的临床疗效和安全性。方法：对126例前列腺增生术后患者静脉滴注甲磺酸帕珠沙星,疗程3～7d。结果：所有患者术后无一例出现明显发热、尿路感染,有效率为87.3%,同时未发现明显不良反应。结论：甲磺酸帕珠沙星对预防前列腺增生术后感染疗效高,安全、不良反应少。     

注射用甲磺酸帕珠沙星在常用输液中的稳定性考察

目的考察甲磺酸帕珠沙星粉针剂在常用输液中的稳定性，并预测其室温贮存有效期。方法采用高效液相色谱法测定甲磺酸帕珠沙星含量，用初匀速法预测其有效期。结果甲磺酸帕珠沙星粉针剂在生理盐水或葡萄糖注射液中12h内稳定，但不宜长时间放置。初匀速法实验结果预测甲磺酸帕珠沙星葡萄糖注射液有效期为30h，甲磺酸帕珠沙星生理盐水注射液有效期为12h。结论初匀速法预测甲磺酸帕珠沙星有效期简便、迅速。用初匀速法预测甲磺酸帕珠沙星稳定性及其有效期为临床用药提供了依据。     

甲磺酸帕珠沙星凝胶剂的制备与质量控制

目的：建立甲磺酸帕珠沙星凝胶剂的制备方法和质量标准。方法：以卡波姆为凝胶基质,制备甲磺酸帕珠沙星凝胶。采用高效液相色谱法测定凝胶中甲磺酸帕珠沙星的含量,色谱柱：Diamonsil C18（250mm×4．6mm,5um）;流动相：乙腈-磷酸三乙胺水溶液（含0．5％磷酸,1％三乙胺）（30：70）;流速：1．0ml·min^-1;检测波长：240nm;进样量：20ul。结果：甲磺酸帕珠沙星在10．54～52．7ug·ml^-1范围内有良好的线性关系,r=0．9993,平均回收率为99．67％,RSD=1．79％。结论：该制备工艺简单、易行,质量控制方法切实可行。     

HPLC法测定甲磺酸帕珠沙星原料及其制剂含量

目的:采用高效液相色谱法测定甲磺酸帕珠沙星原料及其制剂含量.方法:Hypersil C18(5 μm,4.6 mm×250 mm)色谱柱,0.1%磷酸溶液(加磷酸氢二钾80.5 mg)-乙腈(85:15)为流动相,流速1.0ml·min-1,柱温30℃,检测波长243 nm.结果:甲磺酸帕珠沙星在5～500μg·ml-1内与峰面积呈良好的线性关系.甲磺酸帕珠沙星原料(3批)加样回收率99.2%甲磺酸帕珠沙星注射液加样回收率均值为100.1%;甲磺酸帕珠沙星氯化钠注射液加样回收率均值为99.7%.结论:采用HPLC测定原料及其制剂中甲磺酸帕珠沙星含量方法简便,结果可靠.     

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.     

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.     

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.