卡络磺钠树脂复合物的制备及静态交换特性

目的制备卡络磺钠树脂复合物,研究其静态交换反应特性。方法以强碱性氯型阴离子交换树脂Duolite AP 143/1083为载体,静态法制备了卡络磺钠树脂复合物,考察了温度、药物初始浓度和树脂粒径对交换反应的影响,并研究了交换反应动力学和热力学。结果卡络磺钠与DuoliteAP 143/1083的离子交换反应符合二级动力学模型;升高温度可提高载药速度,但载药量下降;随着药物初始浓度的增加,载药量先增加然后达到饱和;减小树脂粒径可加快反应速度,但载药量基本不变。结论最优制备条件确定为温度298.2 K,药物初始质量浓度为1.0 g.L-1,树脂粒径60~75μm。     

阴离子交换树脂与双氯芬酸钠的交换反应特性

目的研究阴离子交换树脂与双氯芬酸钠的交换反应特性。方法以双氯芬酸钠为模型药物,以强碱性阴离子交换树脂(201 ×7)为载体,采用静态法制备药物树脂,考察了阴离子交换树脂不同类型(OH-和Cl-)、树脂粒径以及反应温度对交换过程的影响,并对交换动力学曲线进行了拟合,考察了离子交换反应速率常数、活化能和选择性系数,同时考察了交换反应热力学参数吉布斯自由能变化,反应焓变化和反应熵变化。结果Cl-型OH-型阴离子交换树脂对双氯芬酸钠的载药能力相同。树脂粒径越小,反应温度越高,则反应速率越快。药物树脂间的交换反应符合一级动力学反应,反应活化能约为60·68 kJ·mol-1。在303K、313K和323K三种温度下得到的热力学参数都满足于ΔrGθm<0,ΔrHmθ>0 andΔrSmθ>0。结论药物与树脂的交换过程主要受树脂粒径和反应温度的影响,而且该离子交换反应是吸热反应,即升高温度有助于反应正向自发进行。     

聚苯乙烯磺酸钠理化性质的考察

目的:考察新型药用辅料-聚苯乙烯磺酸钠的基本理化性质.方法:测定聚苯乙烯磺酸钠不同粒径下含水量,湿真密度,交换容量,溶胀率等基本理化性质.结果:聚苯乙烯磺酸钠粒径减小,含水量增大,湿真密度减小,交换容量增大,溶胀率增大.结论:聚苯乙烯磺酸钠的基本理化性质均受粒径影响.     

盐酸倍他洛尔药物树脂的制备及体外释药考察

目的：用静态法制备盐酸倍他洛尔的药物树脂并考察其释药动力学。方法：考察了不同温度和药物浓度对树脂交换速度的影响，并考察了药物树脂复合物在去离子水、0．5，1．0，2．0mol&#183;L^-1氯化钠和在0．5mol&#183;L^-1盐酸以及0．5mol&#183;L^-1氯化钾溶液中的释药动力学。结果：温度升高和药物浓度增大，药物与树脂的交换率增加。盐酸倍他洛尔药物树脂复合物体外释药速率随介质中离子强度的增加而增加。结论：该法制备倍他洛尔树脂复合物方法可行，凝胶型树脂可有效地控制倍他洛尔在体外的释放。     

盐酸倍他洛尔-树脂混悬剂制备工艺研究

目的:考察药物-树脂混悬剂的制备工艺。方法:以阳离子交换树脂(大、小粒径)为载体,盐酸倍他洛尔为模型药物,设计正交试验考察药物与大、小粒径树脂结合的复合物的包封率和载药量,以沉降体积比和再分散性为评价指标筛选出合适的助悬剂,并在人工泪液中比较包衣后药物-树脂混悬剂盐酸倍他洛尔滴眼液的释药动力学。结果:制备的药物-树脂(小粒径)复合物包封率为82.86%、载药量为41.43%,优于大粒径(78.95%、39.48%);以加入卡波姆为助悬剂时混悬剂沉降体积比大,再分散性好,混悬剂稳定。由包衣后的药物-树脂复合物所制备的混悬剂,在人工泪液中的释药动力学与盐酸倍他洛尔滴眼液相似。结论:初步建立了药物-树脂混悬剂的制备工艺,为进一步制备出安全、有效、稳定的药物-树脂眼用混悬剂提供了一定的参考。     

氢溴酸右美沙芬树脂复合物的制备工艺及体外释放行为考察

目的制备氢溴酸右美沙芬树脂复合物,初步考察药物树脂复合物体外释放的影响因素。方法本研究起止时间为 2018年 9月至 2019年 6月,以树脂载药量和药物利用率为指标,通过单因素考察法,筛选了树脂型号、交换温度、药物浓度、药物与树脂的配比、交换时间、交换介质的离子强度等因素对药物树脂复合物制备的影响。采用场发射扫描电子显微镜( FESEM),差示扫描热分析法( DSC)对树脂结构及药物与树脂的结合方式进行剖析。结果成功制备了氢溴酸右美沙芬树脂复合物,优选 AMBERLITE IRP?69树脂,交换温度为 40 ℃,药物浓度为 3.0%,药物与树脂的配比为 1∶1,交换时间为 480min,交换介质为水。药物树脂复合物在 pH1.0盐酸溶液(含 0.4 mol/L氯化钾)中 8h的释放达到 99.40%,在 pH4.0醋酸盐缓冲液(含 0.4 mol/L氯化钾)中 8h的释放达到 100.14%,在 pH6.8磷酸盐缓冲液(含 0.4 mol/L氯化钾)中 8h的释放达到 97.98%。结论最优制备工艺下,树脂载药量达到 933.2 mg/g,药物利用率为 93.30%。药物与树脂的结合方式为离子键结合,药物树脂复合物的释放受离子强度的影响。     

缓释药物的释放体系:苯丙醇胺及其他药物的包衣药树脂系统

离子交换剂是一种固体不溶性高分子聚电解质。它能与周围介质中带相同电荷的流动离子进行交换。一种类型的离子,在交换剂上被另一种离子所置换的交换是可逆的,且能进行化学计算。Keating用磺酸型阳离子交换树脂吸附碱性含氮药物制备的各种制剂,并将其优     

蔗糖八硫酸酯三乙胺梯度法制备重酒石酸长春瑞滨脂质体

 目的：制备重酒石酸长春瑞滨脂质体,并对制备工艺进行考察。方法：以蔗糖八硫酸酯三乙胺（triethylammonium sucrose octasulfate,TEA8SOS）梯度法制备重酒石酸长春瑞滨脂质体,以阳离子交换树脂分离脂质体与游离药物;并以紫外分光光度法和激光粒度仪分别测定重酒石酸长春瑞滨脂质体的包封率和粒径。结果：重酒石酸长春瑞滨脂质体包封率约为95%,粒径为129.5 nm。结论：以蔗糖八硫酸酯三乙胺梯度法制备的重酒石酸长春瑞滨脂质体包封率较高,方法可行。     

阿昔洛韦药物树脂的制备

目的:制备阿昔洛韦药物树脂复合物并对影响因素(温度、流速、粒径、浓度)进行考察。方法:静态交换法和动态交换法。结果:静态制备的优化条件是温度25℃,药物浓度7 mg·mL-1,树脂粒径60—80μm;动态制备的优化条件是温度25℃,药物浓度7．5 mg·mL-1,树脂粒径100-120μm,流速2 mL·min-1。结论:难溶性药物阿昔洛韦可制成药物树脂,且采用静态交换法制备树脂较好。     

更昔洛韦药物树脂的制备及表征

的：研究将更昔洛韦制备成药物树脂复合物。方法：优选药物树脂复合物的制备方法,对药物树脂复合物进行红外光谱分析、差示热分析和热重分析。结果：动态交换法的优化条件为药物浓度4mg·ml^-1,树脂粒径为200～300目,流速1ml·min^-1。结论：动态交换法优于静态交换法,树脂与药物通过离子键的化学吸附结合。     

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.     

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.     

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.