甘草次酸固体脂质纳米凝胶的制备及体外透皮效应

目的制备甘草次酸固体脂质纳米凝胶并考察其体外透皮效应。方法采用微乳液法制备甘草次酸固体脂质纳米粒并考察其包封率、粒径与表面电位,以研和法制备固体脂质纳米粒凝胶;采用改良Franz立式扩散池法进行体外透皮实验,HPLC法测定甘草次酸含量,评价甘草次酸固体脂质纳米粒凝胶的经皮渗透结果。结果甘草次酸固体脂质纳米粒外观为圆球形或椭球形;甘草次酸固体脂质纳米粒的包封率为64.75%±1.36%,粒径范围(46.13±20.10)nm,电位分布范围为(-53.4±7.11)mV。24h甘草次酸固体脂质纳米粒凝胶较甘草次酸固体脂质纳米粒的累积透过量提高66%。结论甘草次酸固体脂质纳米粒凝胶能提高甘草次酸的透皮速率,有望成为甘草次酸透皮给药的新型制剂。     

固体脂质纳米粒作为水杨酸经皮给药载体的研究

目的 考察固体脂质纳米粒作为经皮给药载体对水杨酸经皮吸收的促渗透作用.方法 采用薄膜超声法制备水杨酸固体脂质纳米粒,以改良的Franz扩散池考察其体外透皮特性;并与水杨酸软膏剂比较,考察其促渗作用.结果 制备的水杨酸固体脂质纳米粒均匀圆整,包封率为46.4%,体外透皮特性优于普通软膏剂,24 h后皮肤药物累积透过量为654.3 μg/cm2,皮肤中药物残留量为22.99 μg,均分别显署高于软膏剂组(128.0 μg/cm2和0.84 μg,P<0.05).结论 固体脂质纳米粒作为水杨酸经皮给药载体,可有效促进药物透皮吸收和增加药物在皮肤中储留量,而且可延缓药物的释放,从而有效提高药物疗效及患者依从性.     

美洛昔康固体脂质纳米粒的制备及体外透皮研究

摘 要 目的： 制备美洛昔康固体脂质纳米粒,并考察其透皮吸收行为。方法: 采用热熔乳化超声 低温固化法制备美洛昔康固体脂质纳米粒,并考察其包封率、粒径分布、Zeta电位、微观形态及体外药物释放特性,采用Franz扩散池考察其透皮吸收行为。结果: 美洛昔康固体脂质纳米粒的包封率为（85.6±2.7）%,平均粒径为（213.5±52.6）nm,Zeta电位为（-32.2±3.9）mV,透射电镜显示美洛昔康固体脂质纳米粒粒径均一,成球状分布。其12 h药物累积透皮量显著高于美洛昔康溶液。结论: 美洛昔康固体脂质纳米粒可以显著提高药物累积透皮量,有望成为美洛昔康的新型局部给药制剂。     

正交设计优化伊曲康唑固体脂质纳米粒的处方组成与制备工艺

目的:制备伊曲康唑固体脂质纳米粒(itraconazole solid lipid nanoparticles,ITZ-SLNs)并对其进行物相分析以确定纳米粒的形成。方法:以伊曲康唑(ITZ)为模型药物,硬脂酸为载体材料,采用乳化-低温固化法制备伊曲康唑固体脂质纳米粒(ITZ-SLN),正交试验设计优化处方组成和制备工艺,并对纳米粒的结构形态、粒径、表面电位、包封率、体外释药特性等进行了研究。结果:以优化处方制备的伊曲康唑固体脂质纳米粒为类球形实体,粒径分布比较均匀,平均粒径为dav=(118.2±15.00)nm,Zeta电位为-(37.06±0.53)mV,包封率为(92.11±1.60)%,药物体外释放符合Higuchi方程,经DSC分析证明纳米粒确已形成。结论:伊曲康唑固体脂质纳米粒有望成为新型缓释纳米给药系统。     

固体脂质纳米粒经皮给药系统研究进展

近年来,固体脂质纳米粒(solid 1ipid nanopanicles,SLN)成为经皮给药系统的研究热潮。固体脂质纳米粒通过影响皮肤角质层,作用于皮肤附属器以及改变药物的外在特性使之透过皮肤,从而提高药物皮内滞留量。固体脂质纳米粒可以有效靶向于表皮,为皮肤局部给药提供可能。本文就固体脂质纳米粒特征、透皮特性、透皮机制等进行综述。     

不同剂型青藤碱的体外皮肤渗透性

目的:比较青藤碱微乳、固体脂质纳米粒和脂质体对离体大鼠皮肤的透皮能力。方法:采用改进的Franz扩散池研究三者的透皮行为,采用高效液相色谱法测定接受液中青藤碱浓度并比较三者的经皮渗透能力。结果:t检验结果表明,体外经皮渗透试验中,青藤碱不同剂型的经皮渗透速率差异明显,差异具统计学意义(P<0.01),微乳>固体脂质纳米粒>脂质体。结论:青藤碱微乳有较强的透皮能力,适合青藤碱的新型透皮给药剂型。     

乳化蒸发法制备固体脂质纳米粒

目的：采用乳化蒸发法制备固体脂质纳米粒,并考察其载药性能。方法：对影响固体脂质纳米粒质量的工艺因素和处方因素进行考察和优化设计,得到最优处方。选用模型药物酮洛芬制备载药固体脂质纳米粒,考察其包封率和体外释放行为。结果：所得固体脂质纳米粒平均粒径为（228.2±18.1）nm,多分散系数为（0.217±0.022）,ξ电位为-（21.4±0.6）mV。载药固体脂质纳米粒最佳包封率为（64.1±3.3）%,体外释放行为符合Weibull模型。结论：采用乳化蒸发法制备固体脂质纳米粒是可行的。     

固体脂质纳米粒作为维A酸经皮给药载体的研究

目的:采用固体脂质纳米粒作为维A酸载体以提高其稳定性,增加经皮给药时的局部药物浓度。方法:采用纳米乳法制备维A酸固体脂质纳米粒,通过相图研究确定处方组成并通过单因素试验进行优化,采用葡聚糖G50微型凝胶柱测定包封率。对维A酸固体脂质纳米粒稳定性、释放度、经皮渗透性和皮肤贮留量进行评价。结果:制得的固体脂质纳米粒为球形或类球形粒子,平均粒径为83.2 nm,包封率>95%。4℃,25℃和40℃避光贮存3个月,含量和包封率均无明显变化。其体外释放速率和经皮渗透速率较市售乳膏慢,皮肤贮留量大于市售乳膏。结论:固体脂质纳米粒作为维A酸载体有助于提高其稳定性,增加局部药物浓度。     

固体脂质纳米粒在中药经皮给药中的研究进展

目的:介绍固体脂质纳米粒作为载体应用于中药经皮给药的研究进展。方法:以"固体脂质纳米粒""中药""经皮给药""纳米载体""Solid lipid nanoparticles""Traditional Chinese medicine""Transdermal drug delivery""Nano-carrier"等为关键词,组合查询2000-2014年Pub Med、中国知网全文数据库、维普中文期刊数据库和万方数据库中有关固体脂质纳米粒的常用脂质材料、透皮机制、优劣势及其在中药经皮给药研究进展的相关文献并进行综述。结果与结论:共查阅文献167篇,有效文献32篇。固体脂质纳米粒常用脂质材料为甘油三酯、甘油酯、类胆固醇等,经皮给药时常用表面活性剂有豆磷脂、卵磷脂等。其透皮机制尚不明确,可提高药物物理稳定性、提高难溶性药物生物利用度、降低药物刺激性,同时具有促渗、缓释、靶向作用。其劣势为载药量相对较低。现已有鬼臼毒素、灯盏花素、雷公藤内酯醇、青藤碱固体脂质纳米粒等用于经皮给药中。存在的不足有药物包载有限以及在安全性和有效性方面尚缺乏系统评价等,尚需深入研究。     

雷公藤提取物固体脂质纳米粒水分散体的制备及体外透皮吸收

制备雷公藤乙酸乙酯提取物固体脂质纳米粒水分散体,并初步研究了体外透皮行为.     

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.     

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.