盐酸莫西沙星脂质体的制备及包封率测定方法研究

目的：制备盐酸莫西沙星脂质体,建立盐酸莫西沙星脂质体包封率测定方法。方法：乙醇注入法制备盐酸莫西沙星脂质体,正交试验优选脂质体的最佳处方。采用葡聚糖凝胶柱法、超滤离心法分离脂质体与游离药物,并进行方法学考察,优选出测定盐酸莫西沙星脂质体包封率的方法。结果：盐酸莫西沙星脂质体的最佳处方为：卵磷脂与胆固醇比为 3：1,药脂比为 1：7,水合介质中聚山梨酯20的用量为1%,优化后的包封率为90.73%。葡聚糖凝胶柱法和超滤离心法都能将脂质体与游离药物分离,葡聚糖凝胶柱法的平均柱加样回收率为85.54%~88.15%,超滤离心法的平均加样回收率为94.40%~97.35%。结论：盐酸莫西沙星脂质体的制备工艺稳定,包封率较高。葡聚糖凝胶柱法不适于盐酸莫西沙星脂质体的包封率测定,超滤离心法可高效、准确、方便地测定盐酸莫西沙星脂质体包封率。     

均匀设计法考察不同制备方法对氟尿嘧啶脂质体包封率的影响

目的考察不同制备方法对氟尿嘧啶脂质体包封率的影响,从而优选较好的制备方法.方法分别以薄膜分散法、逆向蒸发法、pH梯度法、以及硫酸铵梯度法制备氟尿嘧啶脂质体,用SephadexG 50葡聚糖凝胶柱分离 高效液相色谱法测定氟尿嘧啶脂质体的包封率,以包封率为指标运用均匀设计法优选制备方法和处方.结果主动载药法尤其是pH梯度法制得的氟尿嘧啶脂质体包封率明显优于被动载药法,包封率顺序为pH梯度法＞硫酸铵梯度法＞逆向蒸发法＞薄膜分散法.采用最优工艺制备氟尿嘧啶脂质体,平均包封率可达60.67%.结论制备方法对氟尿嘧啶脂质体包封率影响显著;pH梯度法能制得包封率较高的氟尿嘧啶脂质体.     

醋酸钙梯度法制备维A酸脂质体

目的:评价醋酸钙梯度法制备维A酸脂质体的可行性,并与薄膜法、逆相蒸发法进行质量比较。方法:采用薄膜法、逆相蒸发法和醋酸钙梯度法分别制备维A酸脂质体,用G-50葡聚糖凝胶柱分离,以紫外分光光度法和纳米激光粒度仪分别测定维A酸脂质体的包封率和粒径,以电子显微镜观察维A酸脂质体的形态。结果:以醋酸钙梯度法制备的维A酸脂质体包封率最高,达90.48%;其外观圆整均匀,平均粒径为35.8nm,4℃放置3mo质量稳定。结论:采用醋酸钙梯度法制备维A酸脂质体包封率较高,方法可行。     

醋酸地塞米松脂质体滴眼液的制备

目的制备醋酸地塞米松脂质体滴眼液,考察包封率及粒径的影响因素并进行质量评价。方法以葡聚糖凝胶分离脂质体和游离醋酸地塞米松;采用紫外分光光度法测定醋酸地塞米松脂质体滴眼液的包封率。考察制备工艺和处方因素对醋酸地塞米松脂质体滴眼液的包封率及粒径的影响。评价醋酸地塞米松脂质体滴眼液的质量。与醋酸地塞米松滴眼液相比,考察醋酸地塞米松脂质体滴眼液的眼部滞留时间。结果通过优化制备工艺和处方,醋酸地塞米松脂质体滴眼液的包封率达88.70%,粒径为133.8nm,醋酸地塞米松脂质体滴眼液的眼部滞留时间是普通滴眼液的4倍。结论制备的醋酸地塞米松脂质体滴眼液包封率较高,粒径小,显著延长了药物的滞留时间,方法可行。     

pH梯度法结合逆向蒸发法制备氟尿嘧啶脂质体

目的：以pH梯度法结合逆向蒸发法制备氟尿嘧啶脂质体,并评价其质量。方法：采用pH梯度法结合逆相蒸发制备氟尿嘧啶脂质体,以包封率为指标进行处方优化;用Sephadex G-50葡聚糖凝胶柱分离-高效液相色谱法测定氟尿嘧啶脂质体的包封率;以激光散射粒径分析仪测定脂质体的平均粒径及Zeta电位,透射电镜观测形态,并初步考察脂质体在室温和4℃冷藏条件下的稳定性。结果：制得的氟尿嘧啶脂质体外观形态圆整,平均粒径为282nm,Zeta电位为-25．9mV,平均包封率为75．39％,4℃冷藏条件下贮存脂质体的稳定性要明显优于室温贮存。结论：运用pH梯度法结合逆向蒸发法能制备包封率较高的氟尿嘧啶脂质体。     

pH梯度法制备氟嗪酸脂质体及质量评价

目的：对用ｐＨ梯度法制备的氟嗪酸脂质体进行质量评价。方法：用Ｓｅｐｈａｄｅｘ－７５葡聚糖凝胶柱分离,紫外分光光度法测定氟嗪酸脂质体包封率并进行体外渗漏测试。结果：当大豆磷脂与胆固醇重比为４∶１,氟嗪酸与磷脂重比分别为１∶１６、１∶８、１∶４时,包封率分别为８８．４％、８６．３％、７４．１％。体外渗漏测试显示,在分别稀释１、５、１０倍后１ｈ测得渗漏率均小于５％。结论：用ｐＨ梯度法制备的氟嗪酸脂质体包封率高,渗漏率低。     

异甘草素脂质体的制备及稳定性考察

目的:制备异甘草素脂质体并考察其包封率及稳定性.方法:采用超声波薄膜分散法制备异甘草素脂质体,正交设计优选制备工艺;透射电镜观察形态;激光粒径仪测定平均粒径;葡聚糖凝胶层析法分离含药脂质体与游离药物并测定包封率;离心加速实验考察脂质体的稳定性.结果:异甘草素脂质体的平均粒径为233.1 nm,跨距为0.74,平均包封率为82.57%,稳定性良好.结论:该法制备异甘草素脂质体工艺可行,质量稳定.     

葡聚糖凝胶柱色谱法测定阿苯达唑纳米脂质体包封率的方法研究

目的：考察用葡聚糖凝胶柱色谱法测定阿苯达唑纳米脂质体包封率的影响因素。方法：考察大、小2种不同粒径（100～300、50～150μm）的葡聚糖凝胶对样品脂质体的分离效果;以方法回收率和脂质体分离比为综合指标,以凝胶柱内径与葡聚糖填充高度比（A）、洗脱流速（B）及上样量（C）为因素设计正交试验,筛选测定脂质体包封率的最优条件,并进行验证试验。结果：小粒径的葡聚糖凝胶对样品分离效果更好;优选测定条件为A：1.2：5、B：5mL·min-1、C：0.5mL;验证试验中平均脂质体分离比（包封率）为（91.56±0.98）%,平均方法回收率为（98.61±0.44）%（n=3）。结论：所建立的阿苯达唑纳米脂质体包封率测定方法准确、重现性好。     

微柱离心-紫外分光光度法测定超氧化物歧化酶模拟物脂质体的包封率

目的:建立超氧化物歧化酶(superoxide dismutase,SOD)模拟物脂质体包封率的测定方法。方法:利用紫外分光光度法测定SOD模拟物的含量,检测波长为371 nm。以薄膜分散法制备SOD模拟物脂质体,采用葡聚糖凝胶-微柱离心-紫外分光光度法测定其包封率。结果:SOD模拟物在60.0～240.0μg.mL-1范围内线性关系良好(r=0.999 3),微柱离心法能有效地将脂质体与游离药物分离,加样回收率测定结果为(99.18±1.05)%,利用该方法测定的SOD模拟物脂质体包封率为(91±1.63)%。结论:紫外分光光度法可以作为SOD模拟物的含量测定方法,微柱离心法操作简单,重现性好,适用于SOD模拟物脂质体包封率的测定。     

姜黄素脂质体的制备及包封率测定

目的：探讨姜黄素脂质体的制备,建立其含量测定方法,测定其包封率。方法：采用薄膜分散法制备姜黄素脂质体,采用超速离心法分离脂质体及游离药物,采用紫外分光光度法（UV）测定姜黄素含量,计算其包封率。结果：采用薄膜分散法制得的姜黄素脂质体为黄色,呈圆形或类圆形,平均粒径为0.49μm,分布均匀,脂质体的平均包封率为96.02%,符合2010版《中国药典》的要求。姜黄素脂质体中姜黄素含量为9.87mg/g,RSD为0.99%。结论：薄膜分散法可以简单快速地制备姜黄素脂质体,操作流程掌握容易,制备的脂质体形态较好、包封率较高;超速离心法与紫外分光光度法结合可以准确、可靠地测定姜黄素脂质体的含量。     

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.