磷酸苯丙哌林缓释片药物动力学研究初步研究

建立了测定苯丙哌林血浆浓度的高铲液相色谱法，并研究了该药的药动学行为， ３条家犬口服８０ｍｇ磷酸苯丙哌林２种制剂后的血药浓度，药动学参数如下：Ｔ１２＝３．８ｈ，ｔｍａｘ＝４．０ｈ，ＡＵＣ－→∞＝１１．６ｍｍｏｌ／Ｌ，ＭＲＴ＝６．５ｈ，Ｆ＝９１．８％。     

磷酸苯丙哌林—β—环糊精包合物的研制

用饱和水溶液和研磨法制备磷酸苯丙哌林（１）的β－环糊精（２）包合物，采用正交试验法探讨了制备包合物的最佳工艺条件。经红外光谱鉴定，１与２确已形成包合物     

磷酸苯丙哌林片溶出度测定方法的建立

目的：建立磷酸苯丙哌林片的溶出度测定方法。方法：采用小杯法,以0．1mol·L-1盐酸溶液200ml为溶出介质,转速为50r．min-1,紫外分光光度法测定,检测波长为270nm。结果：磷酸苯丙哌林按苯丙哌林计在0．0198～0．1984mg·ml-1（r=0．9999）范围内,呈良好的线性关系,平均回收率为99．3％（n=9,RSD=0．5％）。结论：本方法简便、快速、准确,可用于磷酸苯丙哌林片的溶出度测定。     

HPLC法测定磷酸苯丙哌林片的含量

目的建立高效液相色谱测定磷酸苯丙哌林片中磷酸苯丙哌林含量的方法。方法色谱柱以十八烷基硅烷键合硅胶为填充剂;甲醇-0.1mol·L^-1醋酸铵缓冲液（醋酸铵7.7g溶于800ml水中,用冰醋酸调pH为3.3,用水稀释至1000ml）（65：35）为流动相;检测波长为270nm。结果线性关系为Y=0.63015X－3.87007,r=0.9999,线性范围在100.90-1008.96mg·L^-1,平均回收率98.9％（n=9）,RSD=0.60％。结论本法操作简便准确,可作为磷酸苯丙哌林含片中磷酸苯丙哌林含量的质量控制方法。     

阴离子表面活性剂滴定法测定磷酸苯丙哌林口服液的含量

阴离子表面活性剂滴定法测定磷酸苯丙哌林口服液的含量深圳市药品检验所５１８０２９王玉丁波磷酸苯丙哌林口服液（科特口服液）为非麻醉性镇咳药，具有降低肺牵引受体冲动并降低咳嗽中枢兴奋性的作用．近几年来临床应用较为广泛．其含量测定方法，质量标准［１］为提取...     

磷酸苯丙哌林缓释胶囊的释放度测定

目的：建立了UV法测定磷酸苯丙哌林缓释胶囊的释放度。方法：采用《中国药典》2005年版二部附录XD第二法，转速为50r·min^-1，检测波长为270nm。结果：磷酸苯丙哌林在0．03～0．15mg·ml^-1浓度范围内线性线性关系良好（r=0．9999），平均回收率为99．9％，RSD为1．1％（n=9）。结论：用UV法测定磷酸苯丙哌林缓释胶囊释放度方法简单，易于控制其释放度。     

高效液相色谱法测定磷酸苯丙哌林胶囊中磷酸苯丙哌林的含量

目的建立高效液相色谱法测定磷酸苯丙哌林胶囊中磷酸苯丙哌林含量的方法。方法用C18色谱柱（4.6mm×250 mm,5μm）,流动相：甲醇-0.1 mol.L-1醋酸铵缓冲液（用冰醋酸调节pH至3.3）（65∶35）,流速：1.0 mL.min-1 检测波长：270 nm 柱温：室温。结果苯丙哌林的线性范围40.5~1012.0μg.mL-1,r=0.9995,平均回收率为99.2%,RSD=0.8%。结论方法简便、可靠、快速。     

苯丙哌林在纤维支气管镜检查中的应用

目的：研究苯丙哌林在纤维支气管镜检查（纤支镜检查）中的作用，方法：纤支镜检查病人９０例，年龄３８±ｓ９ａ，随机分成３组，每组３０例，一组于术前０．５ｈ口服苯丙哌林４０ｍｇ，一组于术前０．５ｈ口服可待因３０ｍｇ，一组不服任何止咳药物，观察操作时间，术中２％利多卡因溶液用量，病人对操作的耐受性，结果：３组操作时间分别为８．２±１．３ｍｉｎ，８．３±１．３ｍｉｎ和１５．３±２．４ｍｉｎ，术中３组２％利多     

苯丙哌林缓释胶囊人体生物等效性研究

目的评价两种磷酸苯丙哌林制剂的人体生物等效性。方法将18名志愿受试者随机分成2组,分别单剂量交叉1：7服两种制剂,用高效液相色谱法测定血中磷酸苯丙哌林的药物质量浓度,用3P97软件计算药代动力学参数和等效性分析。结果两种制剂的达峰时间（Tmax）分别为（4．28±0．96）h和（4．66±1．28）h,峰浓度（Cmax）分别为（92．85±26．03）ng／mL和（96．93±28．43）ng／mL,0～48h药时曲线下面积（AUC0-48）分别为（2403．06±690．47）ng／mL·h和（2445．50±591．03）ng／mL·h,相对生物利用度为（100．9±26．8）％。结论西南药业股份有限公司研制的磷酸苯丙哌林缓释胶囊与湖北中佳药业有限公司生产的磷酸苯丙哌林缓释片具有生物等效性。     

苯丙哌林在纤维支气管镜检查中的应用

目的：研究苯丙哌林在纤维支气管镜检查（纤支镜检查）中的作用。方法：纤支镜检查病人９０例，年龄３８±ｓ９ａ，随机分成３组，每组３０例。一组于术前０．５ｈ口服苯丙哌林４０ｍｇ，一组于术前０．５ｈ口服可待因３０ｍｇ，一组不服任何止咳药物。观察操作时间，术中２％利多卡因溶液用量，病人对操作的耐受性。结果：３组操作时间分别为８．２±１．３ｍｉｎ、８．３±１．３ｍｉｎ和１５．３±２．４ｍｉｎ，术中３组２％利多卡因液用量为４．５±１．４ｍＬ，４．６±１．３ｍＬ和７．６±１．９ｍＬ，用药组与不服药组有显著差异（Ｐ＜０．０１）。结论：苯丙哌林在纤支镜检查中具有与可待因类似的辅助作用，可缩短操作时间、减少利多卡因用量，但无可待因缺点。     

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.