真武汤颗粒剂制备工艺研究

摘 要 目的：优选真武汤水提液最佳提取工艺及颗粒剂制备方法,为真武汤颗粒剂的开发利用提供参考。方法: 采用加热回流提取方法,通过正交试验设计考察液料比、提取时间及提取次数,以芍药苷含量、苯甲酰新乌头原碱含量和出膏率为考察指标,确定真武汤最优水提取工艺。另外选用粒度合格率、水分、干燥失重、溶化性和休止角等为考察指标,通过单因素试验优选颗粒制备中的辅料配比。结果:芍药苷和苯甲酰新乌头原碱分别在5.45~32.70 μg（r=0.999 6）和3.24~16.80 μg（r=0.999 7）浓度范围内线性关系良好,平均回收率分别为99.62%（RSD=1.34%,n=6）和101.72%（RSD=1.74%n=6）。最优提取工艺为：液料比1∶12,回流提取2次,每次2 h。颗粒最佳成型工艺为：辅料采用糊精与可溶性淀粉的混合物,最佳配比1∶3,所制颗粒的粒度合格率、水分、干燥失重、溶化性和休止角分别为94.12%、4.87%、0.93%、89.23%、36.18°。结论:优化的真武汤回流提取工艺稳定、可行,制备的颗粒成型性和溶化性较好。     

黄麦颗粒制备工艺研究

摘 要 目的： 研究黄麦颗粒的制备工艺,确定最佳工艺条件。方法: 采用单因素筛选法和正交设计法,进行提取工艺和成型工艺优选。结果:最佳工艺为处方量的7味药材,加8倍量水,煎煮2 h,提取3次,合并水提液,减压浓缩、干燥成干浸膏。干膏粉与适量糊精混合均匀后,加40%乙醇湿法制粒,干燥后整粒,即得。结论: 所选工艺科学、合理、稳定,适合工业化生产。     

复方扶正养肝颗粒的制备工艺研究

目的优选扶正养肝颗粒的提取工艺和成型工艺。方法建立毛蕊异黄酮葡萄糖苷的HPLC测定方法,通过正交设计实验确定最佳提取工艺。考察不同辅料及用量,以颗粒一次收率和溶化性等为指标,筛选处方中加入辅料的种类、用量及成型工艺参数。结果扶正养肝颗粒的最佳提取工艺:提取3次,每次加12倍量水,每次2 h;最佳成型工艺:赋形剂为糊精-麦芽糊精(1∶2),稠膏-赋形剂(1∶0.4),润湿剂为体积分数为80%的乙醇,用量为15%。结论扶正养肝颗粒的提取工艺和成型工艺稳定可行,质量可控。     

乳块散结颗粒制备工艺研究

目的 筛选乳块散结颗粒的制备工艺。方法 以丹参素转移率为指标,采用正交试验筛选乳块散结颗粒水提工艺,并考察了醇沉浓度、静置时间和制剂的赋形剂。结果 乳块散结颗粒的最佳提取工艺为药材加8倍量水提取2次,每次2 h;醇沉浓度为75%,静置时间为48 h,赋形剂为可溶性淀粉与糊精（1:1）。结论 优选的乳块散结颗粒制备工艺稳定、可行。     

正交试验法优选宣郁通经汤颗粒的提取工艺

目的 优选宣郁通经汤颗粒的最佳提取工艺。方法 用正交试验法优选宣郁通经汤颗粒水提工艺的加水量、提取时间和次数,以提取液中芍药苷含量和出干膏率为指标,每个因素3个水平,优选最佳水提工艺。结果 宣郁通经汤颗粒的最佳水提工艺为饮片加8倍量水浸泡30 min,提取3次,每次60 min。结论 优选的宣郁通经汤颗粒提取工艺稳定、可行。     

经舒宁颗粒提取纯化工艺优选

摘 要 目的:优选经舒宁颗粒的提取纯化工艺。方法: 以芍药苷的转移率和浸膏得率作为评价指标,采用正交试验对水提条件进行优选,以醇沉前后芍药苷的转移率和干膏量对醇沉条件进行考察。结果:优选出最佳的工艺条件是8倍量的水,提取3次,每次2.5 h,醇沉浓度为70%。结论:优选出的工艺稳定,可行,适合该制剂的批量生产。     

响应面法优化罗麦颗粒成型工艺的研究

摘 要 目的：优化罗麦颗粒剂的最佳成型工艺。方法: 以合格颗粒收率及吸湿性为指标对赋形剂的种类进行筛选,通过对制粒效果的考察,优选赋形剂的最佳混合比例。以合格颗粒收率、溶化性、吸湿性、感官评价的总评“归一值”作为评价指标,选取辅料倍数、乙醇浓度、柠檬酸用量为主要影响因素,采用3因素5水平中心组合设计—响应面法优化罗麦颗粒成型工艺。结果: 确定了糖粉和麦芽糊精为颗粒的赋形剂,且糖粉和麦芽糊精的最佳混合比例为3∶1。罗麦颗粒的最佳成型工艺是赋形剂用量为提取物的5倍量,润湿剂为85%乙醇,柠檬酸含量为0.3%。结论:运用中心组合设计—响应面法制备所得的罗麦颗粒具有合格收率高、吸湿性小、溶化性好、口感柔和且服用量适中等优点,表明优化罗麦颗粒湿法制粒的工艺合理、可行。     

正交试验法优选心舒颗粒的提取工艺

目的 优选心舒颗粒中的醇溶性成分的提取工艺。方法 以干膏得率、丹参酮ⅡA含量为评价指标,选用L₉(3⁴)正交表进行实验。考察提取时间、提取次数、乙醇浓度、乙醇用量对干膏得率和丹参酮ⅡA含量的影响,以多指标综合评分法确定最佳工艺。结果 确定加生药材10倍量的90%乙醇,回流1.5 h,提取2次为最佳方案。结论 最佳工艺基本稳定可行。     

基于熵权法-层次分析法结合响应面法优化养阴润目颗粒的提取工艺

目的 采用多指标综合加权评分法结合响应面法试验，优选养阴润目颗粒的最佳提取工艺。方法 以HPLC测定葛根素、陈皮苷、异阿魏酸的含量，干膏得率及总多糖含量为综合评价指标，采用熵权法-层次分析混合加权法确定各评价指标的权重系数，通过单因素试验及响应曲面法分别考察加水量、提取次数、提取时间对养阴润目颗粒的水提工艺的影响，优选最佳提取工艺参数。结果 按照混合加权法确定的各指标的客观权重进行综合评分，确定养阴润目颗粒的最佳提取工艺条件为加10倍量水，提取3次，每次65 min。验证试验结果显示预测值与实测值相比，RSD值≤3%。结论 优选的提取工艺经验证，稳定、可行且重复性好，可为其后续养阴润目颗粒剂的开发研究提供实验参考。     

赤丹肝纤颗粒的醇提工艺研究

摘 要 目的： 优选赤丹肝纤颗粒的醇提最佳工艺。方法: 以虎杖苷含量为考察指标,先优选出最佳乙醇浓度,再采用L₉(3⁴)正交试验法,考察提取次数、提取时间及乙醇用量对提取效果的影响。结果: 最佳醇提工艺条件为以70%乙醇为溶媒回流提取2次,每次2 h,每次溶媒量为药材量的5倍。结论: 优选的工艺合理可行、重复性良好、提取效率高,适合于工业化生产。     

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.