定眩饮颗粒剂的制备工艺考察

摘要：目的:优选定眩饮颗粒的最佳制备工艺。方法:以芍药苷提取量和干浸膏得率为评价指标,选取煎煮次数、加水倍数、煎煮时间为考察因素,采用正交试验优化处方药材提取工艺;以颗粒的成形率、休止角为评价指标,采用单因素试验优选定眩饮颗粒成型工艺。结果:优选出最佳提取工艺为加10倍量水,煎煮2次,每次1.5 h,芍药苷平均提取量为135.69 mg,干浸膏平均得率为32.22%;成型工艺中浸膏与辅料最佳比例为1∶2,辅料糊精与蔗糖的最佳比例为1∶1。结论:优选的定眩饮颗粒药材提取工艺稳定、可行,所制颗粒成型性和溶化性较好。     

基于星点设计-效应面法联用正交设计优选抗骨质疏松颗粒的制剂工艺

目的 用星点设计-效应面法（CCD-RSM）联用正交实验设计优选抗骨质疏松颗粒的制剂工艺。方法 以溶媒用量、煎煮时间为考察因素,以有效成分补骨脂素、异补骨脂素总量和干膏收率的总评“归一值”（optical density,OD）为评价指标,用CCDRSM确定最佳提取工艺;以颗粒溶化性、吸湿率、水分、成型率、休止角为评价指标,用正交实验优选最佳成型工艺。结果 最佳提取工艺为加水量12倍,提取2次,每次130 min;成型工艺为浸膏与辅料的比例为1∶2,可溶性淀粉与糊精的比例为1∶3,用体积分数为90%的乙醇制粒,75℃干燥,过16目筛整粒,即得。结论 优选的制剂工艺条件稳定、可行,可为抗骨质疏松颗粒的实际生产提供依据。     

复方杨桃颗粒的成型工艺研究

目的 优选复方杨桃颗粒的成型工艺.方法 以吸湿率、成型率、溶化性因素为考察指标,筛选最佳辅料与配比,确定复方杨桃颗粒的成型工艺.结果 最佳成型工艺条件为:干浸膏:可溶性淀粉:糊精=1:1:0.2,90％乙醇为润湿剂,按照该成型工艺制备3批颗粒并作评价.颗粒的成型率可达80％以上,粒度检查、水分测定和溶化性均符合规定,颗...     

祛痹颗粒喷雾干燥工艺的研究

目的：优选祛痹颗粒剂喷雾干燥的最佳工艺条件。方法：采用单因素试验及正交试验法，以药粉收率及其水分为考察指标，对影响祛痹颗粒喷雾干燥过程的因素进行考察。结果：正交试验法设计的三个因素中，以加入的辅料量影响最显著，浸膏的相对密度的影响较显著。最佳辅料为糊精，最佳工艺条件为：浸膏含固量：糊精=1：0．6，进风温度230℃，浸膏相对密度为1.03。结论：采取喷雾干燥工艺生产的祛痹颗粒吸湿率低，能有效地提高其稳定性。     

复方丹路颗粒成型工艺研究

目的:研究复方丹路颗粒的提取方法和成型工艺。方法:通过单因素试验法,考察水提法的浸泡时间、加水量、提取时间和提取次数;以颗粒的吸湿性、溶化性、颗粒外观、成型率、水分以及测定其临界相对湿度等为考察指标,筛选合适的辅料及用量,优选出复方丹路颗粒最佳的成型工艺。结果:复方丹路颗粒最佳成型辅料为蔗糖,干膏粉与辅料按1∶1.0～1∶1.1混合均匀,以90%乙醇为润湿剂,所得颗粒成型率高,临界相对湿度为70.0%,休止角、溶化性以及颗粒粒度等均合格。结论:该颗粒剂选用辅料合理,制备工艺稳定可靠,为复方丹路颗粒实现工业生产提供参考依据。     

复方熊胆茵陈颗粒的制备工艺研究

目的:制备复方熊胆茵陈颗粒,优选复方熊胆茵陈颗粒剂成型工艺。方法:以颗粒的成型率、休止角、堆密度、溶化性为指标筛选合适的辅料,以口感、成形性为指标筛选最佳矫味剂,并以水分控制确定干燥时间,以绿原酸有无被破坏来确定干燥温度。并了解颗粒的吸湿性及相对临界湿度,控制颗粒的贮藏条件,确保颗粒的质量。结果:复方熊胆茵陈颗粒的最佳配方为复方熊胆茵陈浸膏,加入与熊胆粉混匀的辅料(蔗糖:糊精)以1:1.5:1.5混合,制软材,12目过筛,干燥温度为65℃,10目整粒。结论:筛选得到的复方熊胆茵陈颗粒剂制备方法简便可行,成型工艺稳定可控,建议密闭、置干燥阴凉处保存。     

白屈菜胶囊成型工艺

目的 探讨白屈菜胶囊的成型工艺.方法 以吸湿率为指标考察辅料的种类及配比;以颗粒吸湿率和成型率为指标,筛选最佳成型工艺条件,并考察颗粒的休止角,堆密度,临界相对湿度.结果 主药与辅料（可溶性淀粉：糊精=3：1）按4.5的比例混匀,加入75％乙醇制软材,20目筛制粒,所得颗粒的休止角为18.8°,堆密度为0.47 g/mL,临界相对湿度为80％.结论 该成型工艺合理、可行,为大生产提供了科学依据.     

基于QbD的二冬汤颗粒制备工艺及质量控制

目的 基于质量源于设计(quality by design,QbD)理念对二冬汤颗粒制备工艺进行研究,并对其质量进行控制。方法设计L9(34)正交试验法,以出膏率、指标成分转移率、总多糖为评价指标,AHP-CRITIC混合加权法优选二冬汤最佳提取工艺;以成型率、溶化率、休止角、吸湿率为考察指标,采用星点设计-效应面法结合熵权法优化二冬汤颗粒成型工艺;以相对均齐指数、松密度、振实密度、水分、吸湿率、休止角、豪丝纳比为指标,建立物理指纹图谱,评价颗粒质量一致性。结果 二冬汤的最佳提取工艺为加水量12倍,不浸泡,提取3次,每次30 min。3批重复验证试验综合评分均数为54.24,RSD为1.09%。二冬汤颗粒的最佳成型工艺：干膏粉与辅料比为1∶0.6,润湿剂体积分数87%,润湿剂用量16%,在80℃下干燥30 min。5批颗粒物理指纹图谱相似度均>0.99。结论 该法稳定可行,可为二冬汤颗粒工业化生产以及该制剂的进一步研究提供方向。     

肝清颗粒的制剂工艺研究

目的优选肝清颗粒的制剂工艺。方法以制粒情况、成型率、溶化性、休止角和吸湿率为评价指标,采用正交试验法优选制剂工艺条件。结果肝清颗粒最佳制粒工艺条件为：浸膏粉和混合辅料（糖粉：糊精=2.5：1）按5.7：6.3比例混匀,以65%糖浆为粘合剂,粘合剂用量为混粉总量的40%。制备的成品颗粒评价指标均符合要求。结论优选的肝清颗粒制剂工艺合理可行,成本低,为进一步制剂研究和临床应用提供了试验依据。     

柔肝宝颗粒剂的成型性工艺

目的:正交试验法优选柔肝宝颗粒剂的成型性工艺。方法:考察常用辅料糊精、乳糖、可溶性淀粉、微晶纤维素及混合辅料,对颗粒成型率、吸湿率、休止角的影响,并采用正交试验法,以辅料用量、乙醇体积分数、乙醇用量为考察因素,优选柔肝宝颗粒最佳成型性工艺。结果:以乳糖和糊精按1∶1混合为成型辅料,浸膏粉(g)与辅料(g)配比为1∶0.8,乙醇体积分数为85%,浸膏粉(g)与乙醇量(mL)比为5∶1,为减少水分对药物质量的影响,环境湿度应控制在67%以下。结论:该工艺可靠、稳定、重复性好,符合《中国药典》2015年版四部"颗粒剂"各项要求,为中试及大生产提供了参考依据。     

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.