溴吡斯的明磷脂复合物制备工艺

目的:星点设计-效应面法优化溴吡斯的明磷脂复合物制备工艺。方法:以溶剂挥发法制备溴吡斯的明磷脂复合物,以药物与磷脂的复合率为评价指标,采用单因素方法对溴吡斯的明磷脂复合物制备工艺影响因素的重要性进行考察,用星点设计对显著性因素进行优化,并且进行多元线性回归与二项式方程拟合,采用效应面法选取较佳工艺条件,并进行预测。结果:效应面法优选出的最佳工艺为:磷脂与溴吡斯的明以8∶1投料,主药质量浓度为4g.L-1,反应温度为40℃,以优化条件制备溴吡斯的明磷脂复合物,复合率为(84.02±1.68)%,与二项式拟合方程预测结果相差小于2%。结论:应用星点设计-效应面法优化溴吡斯的明磷脂复合物制备工艺,能够快速方便地得到最佳制备工艺,预测性良好。     

星点设计-效应面法优化美斯地浓聚乳酸纳米粒处方

目的星点设计-效应面法优化美斯地浓聚乳酸纳米粒处方。方法以复乳液中干燥法制备美斯地浓聚乳酸纳米粒,以包封率和载药量为评价指标,在单因素试验的基础上,用星点设计对显著性因素进行优化,并进行二项式方程拟合,以效应面法选取较好的工艺条件进行预测。结果以效应面法优选出的最佳工艺为:美斯地浓投药量为49.20 mg,PLA浓度为3.31%,PVA浓度为3.41%。制备的美斯地浓聚乳酸纳米粒平均包封率和载药量分别为(51.98±1.28)%和(7.01±0.31)%(n=3),与二项式拟合方程预测值相差<2%。结论应用星点设计-效应面法优化美斯地浓聚乳酸纳米粒制备工艺,能够快速、准确的得到最佳制备工艺,预测性良好。     

星点设计-效应面法优化α-细辛脑脂质体喷鼻剂的制备工艺

目的:采用星点设计-效应面法优化α-细辛脑脂质体喷鼻剂的制备工艺。方法:以乙醇注入法制备α-细辛脑脂质体喷鼻剂,采用星点设计-效应面法优化制备工艺,在单因素试验的基础上以磷脂含量、磷脂与胆固醇的质量比和磷脂与药物的质量比为自变量,以包封率为因变量,优化处方工艺,进行验证试验并在电镜下观察脂质体形态。结果:二项式方程拟合度高(R2=0.9074),预测性好;星点设计-效应面法优选出的最佳工艺条件为磷脂含量为4.5%、磷脂与胆固醇的质量比为7.5、磷脂与药物的质量比为45,测得包封率为68.1%;最佳工艺验证结果与二项式拟合方程预测值偏差为1.73%;制备的脂质体形态完整,双分子膜结构清晰,均属于单室脂质体。结论:应用星点设计-效应面法能够精确有效地优化α-细辛脑脂质体喷鼻剂的制备工艺,稳定可行。     

星点设计-效应面法优化水飞蓟素固体脂质纳米粒的制备

以冷却-匀质法制备水飞蓟素固体脂质纳米粒,采用星点设计-效应面法优化制备工艺,以平均粒径、包封率、载药量为评价指标,考察了药物与Compritol 888 ATO的重量比、乳化剂用量、泊洛沙姆占乳化剂的比例、乳匀压力4因素对制备工艺的影响,对结果分别进行多元线性和二项式方程拟合,用效应面法预测最佳工艺条件.结果表明,各指标的二项式拟合方程均优于多元线性回归方程,以优化条件制备的样品平均粒径为190.9nm、包封率为95.9%、载药量为8.6%.     

星点设计-效应面法优化鬼针草挥发油β-环糊精包合物制备工艺

目的:探讨星点设计-效应面法优化鬼针草挥发油β-环糊精包合物制备工艺。方法:采用液-液包合法制备鬼针草挥发油β-环糊精包合物,以β-环糊精与鬼针草挥发油的投料比、包合时间、包合温度为考察因素,以包合物收得率和挥发油包封率为考察指标,按星点设计的原理安排进行实验,并对实验数据进行多元线性回归和二项式拟合处理数据,建立指标与因素之间的数学关系,经效应面法预测最佳工艺条件,并做验证试验。结果:2个指标二项式拟合方程均优于多元线性拟合方程,效应面优化后得最佳包合条件为投料比17 g.mL-1,包合时间330 min,包合温度38℃。结论:星点设计-效应面优化法适用于鬼针草挥发油β-环糊精包合物制备工艺的研究,所建立的数学模型预测性良好。     

星点设计-效应面法优化流化床制备盐酸普萘洛尔微囊工艺

目的优化盐酸普萘洛尔微囊的制备工艺。方法采用流化床制备普萘洛尔微囊,以平均粒径,包封率、载药量及总评归一值为评价指标,并运用星点设计考察囊材液流速、喷雾压力对制备工艺的影响,对结果进行多元线性和二项式拟合,效应面法选取最佳工艺条件进行预测分析。结果从复相关系数上看,各指标二项式拟合方程均优于多元线性回归方程,最佳工艺参数:囊材液流速1.00 mL·min-1,喷雾压力0.65 bar,在此工艺条件下得到微囊粒径为300μm,载药量为20.54%,包封率达89.63%。结论优选普萘洛尔微囊的流化床制备工艺稳定可行,包封率高,有利于工业化生产。     

星点设计-效应面法优化阿德福韦-β-环糊精包合物制备工艺的研究

目的：星点设计–效应面法优化阿德福韦包合物的制备工艺。方法以饱和水溶液法制备阿德福韦-β-环糊精包合物,采用星点设计优化制备工艺,以β-环糊精与阿德福韦的投料配比、包合时间、包合温度为自变量,包合率、收率为因变量,分别进行多元线性回归和二项式方程拟合,依据最佳数学模型描绘效应面选择最佳处方工艺进行验证试验。结果二项式方程拟合度较高,预测性好,相关系数r＝0.965;效应面法优选出的最佳工艺为：β-环糊精与阿德福韦的投料配比约为3∶1,包合时间为5 h,包合温度为60℃。最佳工艺验证试验结果与二项式拟合方程预测值偏差为（1.31±0.69）%。结论应用星点设计-效应面优化法能够精确有效地优化阿德福韦-β-环糊精包合物的制备工艺,优选出的最佳工艺稳定可行,可用于工业生产。     

星点设计-效应面法进行蛇床子素脂质体处方优化的研究

目的:以包封率为指标进行蛇床子素脂质体的处方优化研究,并对其质量进行考察。方法:以薄膜蒸发法制备蛇床子素脂质体。采用星点设计-效应面法优化处方,以包封率为因变量,大豆卵磷脂浓度、脂药比、表面活性剂含量为自变量建立多元二次回归方程,用效应面法预测较优处方并进行验证。结果:蛇床子素脂质体的多元二次回归方程为:Y1=0.935 69+0.010 124X1+0.038 691X3-0.024 32X21+0.025 741X1X2-0.054 236X22-0.026 579X2X3-0.109 707X23(r=0.953 7,P<0.05),最佳处方分别为大豆卵磷脂浓度为24.93mg·m L-1,脂药比为22.66∶1(mg·mg-1),表面活性剂含量1.67%,该处方条件下,3批蛇床子素脂质体样品的平均包封率94.98%。结论:用星点设计-效应面法优选蛇床子素脂质体的制备工艺预测性好,制备的脂质体包封率高。     

三七皂苷长循环纳米粒制备及其体外溶出行为

目的:星点设计-效应面法优化复乳化法制备三七皂苷长循环纳米粒(PNS-LCN)并对其进行体外溶出行为研究。方法:以三七皂苷(PNS)浓度、油相中乳化剂浓度以及壳聚糖的浓度为考察因素,包封率、载药量、平均粒径及分散性为考察指标,根据星点设计原理进行实验安排,并用二项式拟合建立指标与因素之间的数学关系,经效应面法预测最佳工艺条件;采用动态透析法考察了PNS与PNS-LCN的体外溶出行为。结果:各指标的二项式拟合方程较好,以优化条件制备的样品包封率为(52.8±0.7)%、载药量为(13.1±0.6)%、平均粒径为(152.6±4.5)nm、分散性为(0.24±0.04);PNS-LCN中药物的释放显著慢于原料药磷酸盐缓冲溶液的释放。结论:星点设计-效应面法适用于PNS-LCN的工艺优化,所建立的数学模型预测性良好;PNS-LCN体外释药具有缓释效果。     

Plackett-Burman设计与星点设计-效应面法优化珠子参皂苷磷脂复合物制备工艺

目的:优化珠子参皂苷磷脂复合物的制备工艺。方法:以溶剂挥发法制备珠子参皂苷磷脂复合物;以复合率为评价指标,采用Plackett-Burman设计确定珠子参皂苷磷脂复合物复合工艺的主要影响因素、星点设计优化主要影响因素的水平、效应面法预测最佳工艺。结果:投料比、皂苷的质量浓度和反应温度对磷脂复合物形成具有显著影响;星点设计中的二项式方程拟合度较高(复相关系数R为0.949 8),效应面法优化的最佳工艺为磷脂与珠子参皂苷投料比3∶1、皂苷质量浓度10 mg/ml、反应温度40℃。最佳工艺试验验证结果与二项式拟合方程预测结果的偏差小于2%。结论:优化得到的珠子参皂苷磷脂复合物最佳制备工艺稳定、可行。     

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.