曲马多缓释多囊泡脂质体的制备和释放度影响因素研究

目的 制备包封率高和缓释作用好的PGE修饰的曲马多缓释缓释多囊泡脂质体,并与逆相蒸发法制备的曲马多普通脂质体比较其体外释药性能.方法 用复乳法制备曲马多缓释多囊泡脂质体;非火焰原子吸收分光光度法测定曲马多含量;磷脂酶试剂法测定脂质体中磷脂的浓度;测定包封率和体外释药性.结果 曲马多缓释多囊泡脂质体平均粒径为31.3μm,跨距为1.0;曲马多包封率可高达80%以上;曲马多缓释缓释多囊泡脂质体的体外释药符合一级释药规律,释药时间为72h,比逆相蒸发法制备的曲马多普通脂质体延长16.95（由原来为释药时间37.7h延长8.4倍推出）倍;经差示热分析发现辅助膜稳定剂有明显的膜稳定作用.结论 曲马多缓释多囊泡脂质体包封率高,并具有良好的缓释作用.     

吸附和包埋法制备洛美沙星淀粉微球及其体外释放比较研究

目的制备盐酸洛美沙星淀粉微球,并对其体外释药模式进行研究。方法以盐酸洛美沙星为模型药物,采用吸附载药法和包埋载药法制备了载药淀粉微球,通过测定微球载药量、包封率和在不同的释放介质中的体外释放情况,对上述2种方法制备的载药微球进行质量评价。结果吸附法制备的载药微球的平均载药量为14.54μg·mg^-1,药物包封率为39.72%;而包埋载药法制备的淀粉微球的平均载药量为19.32μg·mg^-1,药物包封率为48.95%。体外释药特性研究表明它们具有缓释特性,其中包埋载药法制备的淀粉微球比吸附载药法制备的淀粉微球有更好的缓释能力,在不同的释放介质中释药曲线也有所不同,在模拟胃液中累计释药量只能得到70%;而在模拟肠液中累计释药量能达到80%以上。结论吸附载药法和包埋载药法制备的载药淀粉微球都具有缓释作用,但后者体外释药具有更明显的缓释效果。     

吸附和包埋法制备洛美沙星淀粉微球及其体外释放比较研究

目的 制备盐酸洛美沙星淀粉微球,并对其体外释药模式进行研究。方法 以盐酸洛美沙星为模型药物,采用吸附载药法和包埋载药法制备了载药淀粉微球,通过测定微球载药量、包封率和在不同的释放介质中的体外释放情况,对上述2种方法制备的载药微球进行质量评价。结果 吸附法制备的载药微球的平均载药量为14.54 µg·mg^-1,药物包封率为39.72%;而包埋载药法制备的淀粉微球的平均载药量为19.32 µg·mg^-1,药物包封率为48.95%。体外释药特性研究表明它们具有缓释特性,其中包埋载药法制备的淀粉微球比吸附载药法制备的淀粉微球有更好的缓释能力,在不同的释放介质中释药曲线也有所不同,在模拟胃液中累计释药量只能得到70%;而在模拟肠液中累计释药量能达到80%以上。结论 吸附载药法和包埋载药法制备的载药淀粉微球都具有缓释作用,但后者体外释药具有更明显的缓释效果。     

半乳糖化阿霉素白蛋白纳米粒的制备及其质量评价

目的:制备半乳糖化阿霉素白蛋白纳米粒,并考察了其形态、粒径、载药量、包封率和体外释药特性.方法:采用相分离法制备阿霉素白蛋白纳米粒,并在其表面偶联半乳糖苷,使之成为半乳糖化白蛋白纳米粒.激光扫描电子显微镜观察纳米粒的形态,马尔文激光粒度仪测定其粒径分布.采用紫外分光光度法测定纳米粒的载药量和包封率,并初步研究其体外释药特性.结果:电镜结果显示阿霉素纳米粒呈类球型,平均粒径为316.3 nm,纳米粒载药量为3.12%,包封率达91.82%,48 h体外累积释药率为55.71%.结论:本方法制备阿霉素纳米粒工艺简单且包封率较高.体外释药结果显示半乳糖化阿霉素白蛋白纳米粒具有明显的缓释作用.     

SPG膜乳化法制备槲皮素缓释微球的工艺优化与表征及体外释放研究

目的 以槲皮素作为模型药物,制备聚乳酸-羟基乙酸共聚物(PLGA)缓释微球,考察其粒径及其分布、形态、包封率、载药量和体外释药性质.方法 采用SPG膜乳化法制备微球,单因素法初步优化制备处方;粒径分析仪检测微球的粒径及其分布;光学显微镜观察微球形态;通过紫外分光光度法测定微球的包封率和载药量;利用直接释药法和超速离心法...     

奥沙普秦壳聚糖-海藻酸钠缓释微球的制备

目的：目的：选择奥沙普秦作为模型药制备壳聚糖-海藻酸钠缓释微球。方法：采用滴制法制备奥沙普秦壳聚糖-海藻酸钠缓释微球，通过正交试验设计优化了处方和工艺，考察其理化特征及体外释药行为。结果：优化处方制得的微球包封率及载药量分别为98．36％和16．26％，平均粒径为（346．6±164．1）μm；1h药物释放达到36％，随后药物的释药行为是一个缓释过程。结论：制得了载药量较大，包封率较高的奥沙普秦壳聚糖-海藻酸钠缓释微球。     

透明质酸修饰的PAMAM纳米胶束的制备及性质研究

目的采用透明质酸(HA)修饰聚酰胺-胺(PAMAM)树状大分子,以姜黄素、阿霉素为模型药物,构建HA-PAMAM纳米胶束肿瘤主动靶向给药系统。方法采用酰胺化反应合成不同透明质酸取代度的HA-PAMAM;采用溶剂挥发法制备HA-PAMAM单药和双药联合载药胶束;采用高效液相色谱法测定姜黄素、阿霉素的包封率和载药量;通过体外透析法研究载药胶束的释药特性。结果采用溶剂挥发法制备阿霉素、姜黄素单药或联合载药胶束,载药胶束的包封率与载药量较高(姜黄素分别为66.70%、6.57%,阿霉素分别为82.14%、33.15%)。HA-PAMAM载药胶束体外释放显示出良好的缓释性能。结论透明质酸修饰的PAMAM是一种具有良好肿瘤靶向性应用前景的纳米载药系统。     

球结膜下注射用西罗莫司缓释微球的制备及其体外释药性能

目的使用3-羟基丁酸-co-3-羟基戊酸共聚物制备西罗莫司缓释微球,为预防和治疗角膜移植术后免疫排斥反应奠定基础。方法采用乳化-溶剂挥发法制备微球,正交实验法优化,测得载药量、包封率等指标,结合光镜观察其形态特征,得出最佳制备条件后,模拟眼内前房环境检测其体外释药性能。结果微球制备工艺稳定,重复性好。微球成球率高,形态圆整,表面光滑,载药量为(37.34±1.25)%,包封率为(99.63±0.93)%,能够在体外稳定缓释,500 h累积释药率为71%。结论西罗莫司缓释微球表征良好,载药量、包封率较高,有望发挥稳定释药的临床作用。     

2种骨架材料制备盐酸小檗碱囊泡的比较

目的 比较胆固醇和β-谷甾醇作为囊材制备的盐酸小檗碱囊泡的特性和体外释药差异。方法 采用薄膜蒸发法用2种囊材分别制备盐酸小檗碱囊泡,光学显微镜观察比较囊泡形态,微粒分析仪评价囊泡粒径分布差异;采用HPLC测定盐酸小檗碱囊泡包封率和载药量,比较2种囊泡的体外释放情况,并考察温度对囊泡稳定性的影响。结果 镜下观察2种囊材制备的囊泡圆整度均较好,粒径分布范围比较相似;用胆固醇和β-谷甾醇制备的囊泡包封率分别为28.5%和25.21%,载药量分别为1.32%和1.26%;体外释放试验中,在人工肠液和人工胃液中的胆固醇囊泡12 h累积释放百分率在50%左右,而β-谷甾醇囊泡的累积释放百分率>70%;40℃以下放置8 h,温度对2种小檗碱囊泡的包封率影响较小,当温度高于40℃时,2种小檗碱囊泡的包封率均显著降低。结论 用薄膜分散法制备的2种小檗碱囊泡镜下形态相似,包封率近似;用β-谷甾醇制备的囊泡释药快,释药量多;40℃以下放置稳定性均较好。β-谷甾醇作为载体材料制备囊泡具有可行性。     

普罗布考微囊的制备与性质考察

目的:研究普罗布考微囊的制备工艺,考察其体外释药特性.方法:用复凝聚法制备普罗布考微囊,以包封率为指标,用正交试验设计法对微囊的制备工艺进行研究,对其形态、体外释药特点等进行研究.结果:当囊心与囊材比为1:3、搅拌速率为200r/min、成囊温度为60℃时,制得的普罗布考微囊囊形圆整光滑,囊壁清晰,粒径均匀,平均包封率可高达74.57%,载药量平均为17.93%,囊径为35~95μm,24h累积释药量93.61%.结论:制备的普罗布考微囊工艺简单、可靠,具有缓释效果.     

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.

---

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.