糠酸莫米松固体脂质纳米粒的制备

目的：研究糠酸莫米松固体脂质纳米粒的处方和制备工艺，并对其质量进行评价。方法：用乳化-溶剂挥发法制备糠酸莫米松固体脂质纳米粒，以包封率为指标采用正交设计法优选处方，用透射电镜和激光粒径测定仪测定纳米粒的形态和粒径，用低速离心法测定药物的包封率。结果：制得的糠酸莫米松固体脂质纳米粒形态规整，几呈球形，体积均粒径为73．8nm，包封率为（92．8±0．89）。结论：本研究所得的处方和工艺可制备性能优良的糠酸莫米松固体脂质纳米粒。     

褪黑素固体脂质纳米粒的制备及理化性质

考察不同的处方对褪黑素固体脂质纳米粒粒径和包封率等理化性质的影响，并进行其体外释放实验。结果表明，以单硬脂酸甘油酯为脂质材料，乳化超声法制备固体脂质纳米粒，平均粒径为（62．4±1．5）nm，ζ电位为（-7．0±0．2）mV，平均包封率为（64．6±3．8）％；药物的体外释放符合Weibull模型。     

青藤碱固体脂质纳米粒的制备

目的：以山嵛酸甘油酯为载体材料制备青藤碱固体脂质纳米粒并评价其质量。方法：采用乳化蒸发一低温固化法制备青藤碱固体脂质纳米粒，以正交设计优化其处方和制备工艺。对其粒径、形态、表面电位、包封率等理化性质进行研究，并考察其稳定性。结果：所制固体脂质纳米粒外观形态圆整，平均粒径为208．7nm，Zeta电位为-38．5mV，平均包封率为65．7％。4℃放置2个月，粒径、包封率无明显变化。结论：青藤碱固体脂质纳米粒的制备，为开发其新制剂奠定了实验基础。     

氟尿苷二醋酸酯固体脂质纳米粒的研制及质量评价

目的：对氟尿苷二醋酸酯固体脂质纳米粒的制备工艺和含量测定方法进行研究，并对其质量进行评价。方法：采用薄膜超声分散法制备氟尿苷二醋酸酯固体脂质纳米粒，并对其包封率、形态等性质进行研究。结果：制得氟尿苷二醋酸酯固体脂质纳米粒形态均匀圆整、粒径范围为（215．3±83．1）nm，包封率为98．27％，裁药量为8．20％。结论：选择薄膜超声分散法制备氟尿苷二醋酸酯固体脂质纳米粒方法可行，为开发氟尿苷新型注射制剂提供了实验依据。     

Box-Behnken效应面法优化姜黄素正负离子固体脂质纳米粒的处方

目的 采用Box-Behnken效应面法筛选姜黄素正负离子固体脂质纳米粒的最优处方.方法 采用乳化蒸发-低温固化法制备姜黄素的固体脂质纳米粒,以固体脂质的质量、卵磷脂的质量和混合表面活性剂为考察对象,以包封率和脂质载药量为考察指标,利用3因素3水平Box-Behnken效应面设计法筛选姜黄素固体脂质纳米粒的最优处方.结果 按最优处方制备固体脂质纳米粒的包封率为94.20％ ±2.55％、脂质载药量为3.49％±0.11％,平均粒径为194.9 ±12.0 nm,Zeta电位为-28.15 ±2.72 mV.结论 采用Box-Behnken效应面法优化姜黄素正负固体脂质纳米粒的处方是有效、可行的.     

醋酸泼尼松龙固体脂质纳米粒的试制

采用乳化蒸发-低温固化法制备了醋酸泼尼松龙固体脂质纳米粒,采用正交实验设计优化处方,并考察了理化性质。结果表明,所得制品呈类球状,粒径较均匀,平均粒径为（187±15）nm,载药量为4.8%,包封率79.4%。     

西罗莫司固体脂质纳米粒的制备及在大鼠体内的相对生物利用度

采用溶剂扩散法制备西罗莫司固体脂质纳米粒，考察了分散介质和投药量对纳米粒粒径、表面电位、包封率的影响。将西罗莫司固体脂质纳米粒对正常SD大鼠给药，以口服液为对照，通过测定血药浓度的经时变化，考察固体脂质纳米粒的相对生物利用度。结果表明，以0．2％胆酸钠为分散介质的制品，ζ电位绝对值比以0．2％聚乙烯醇为分散相的制品显著增大，包封率由97．3％降至62．9％。处方中投药量增加，包封率下降。与口服溶液剂相比，西罗莫司固体脂质纳米粒的达峰时间tmax无明显改变，但峰浓度Cmax提高了约1．2倍，相对生物利用度为口服液的139．0％。     

银杏内酯PELGE纳米粒的制备及理化性质

采用共沉淀法制备银杏内酯PELGE纳米粒,正交试验设计优化处方,并考察了优化制品的外观和体外释放行为.结果表明,所得纳米粒外观圆整,包封率为（66.9±1.7）%,粒径为（123.3±44.0）nm,体Pb24h累积释放率为60.2%.     

长春西汀固体脂质纳米粒的制备及其性质考察

目的制备长春西汀固体脂质纳米粒,为长春西汀新型给药系统的开发与应用提供实验基础。方法以长春西汀为模型药物、山嵛酸甘油酯为载体材料,采用热熔超声法制备长春西汀固体脂质纳米粒,并通过正交试验设计对处方进行优化。以包封率为评价指标,对其形态、体外释放度、短期稳定性等性质进行了考察。结果制备的纳米粒为球形及类球形,粒径为152.3 nm,包封率为93.68%,72 h体外累积释放71.84%,4℃下放置2个月稳定。结论热熔超声法可用于制备长春西汀固体脂质纳米粒,该纳米粒具有明显的缓释特征,可进一步进行体内释药行为的考察。     

基于TPGs表面修饰的雷公藤甲素固体脂质纳米粒的制备与质量评价

目的 制备D-α-维生素E聚乙二醇1000琥珀酸酯（TPGs）修饰的雷公藤甲素固体脂质纳米粒（TPGs-Tri-SLNs）,并评价其质量。方法 采用热熔乳化-超声法制备TPGs-Tri-SLNs,并以山嵛酸甘油酯浓度（X₁）,大豆磷脂与TPGs比例（X₂）和山嵛酸甘油酯与药物比例（X₃）作为考察因素,以TPGs-Tri-SLNs的粒径分布（Y₁）和药物包封率（Y₂）作为评价指标,通过中心复合设计-效应面法优化TPGs-Tri-SLNs的处方,粒度分析仪测定其粒径分布,透射电镜观察其微观形态,并考察了TPGs-Tri-SLNs的体外药物释放特性。结果 TPGs-Tri-SLNs的最佳处方组成为：山嵛酸甘油酯浓度为10%,大豆磷脂与TPGs比例4：1,山嵛酸甘油酯与药物比例为60：1,按照最优处方制备3批TPGs-Tri-SLNs的平均粒径为（107.8±16.9）nm,包封率为91.4%±1.1%;在透射电镜下可以观察到TPGs-Tri-SLNs呈球型分布,表面光滑;TPGs-Tri-SLNs在前4 h内药物释放较快,后期释药速率较为平稳,24 h药物释放可以达到85%。结论 通过中心复合设计-效应面法优化并得到TPGs-Tri-SLNs的最优处方,处方设计合理,制备工艺简单。     

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.     

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.