甲氧氯普胺口崩片的制备及体外溶出度考察

摘 要 目的： 制备甲氧氯普胺口崩片并优化处方,并对其体外溶出度进行考察。方法: 采用全因子试验设计,以填充剂配比（X₁）、崩解剂（X₂,%）用量为影响因素,以脆碎度（Y₁,%）、崩解时限（Y₂,s）、甲氧氯普胺在15 min的溶出度（Y₃,%）为片剂考察指标优化处方;并考察其在4种溶出介质中的溶出行为。结果: 甲氧氯普胺口崩片的最优处方组成为：填充剂甘露醇与微晶纤维素比例为2.5∶1、崩解剂占片重为6.5%。甲氧氯普胺口崩片在4种溶出介质中累积溶出度均大于80%。结论:甲氧氯普胺口崩片处方设计合理,制备工艺可行,质量可控。     

兰索拉唑肠溶微丸型口崩片的制备研究

摘 要 目的：制备兰索拉唑肠溶微丸并压制成口崩片,评价耐酸性和释放度。方法: 采用流化床包衣法制备兰索拉唑肠溶微丸,考察了丙烯酸树脂L30D 55和丙烯酸树脂NE30D配比、增塑剂用量和压片主压力对兰索拉唑肠溶微丸型口崩片的耐酸性和释放度的影响,并采用f2相似因子法评价了自制兰索拉唑肠溶微丸型口崩片与市售制剂的体外释放相似性。结果:选用微晶纤维素丸芯平均粒径为150~180 μm载药,隔离层增重为10%,丙烯酸树脂L30D 55和丙烯酸树脂NE30D配比为8∶〖KG-*2〗2,肠溶衣包衣增重为30%,增塑剂用量为20%,压片主压力为10~16 kN,制备的兰索拉唑肠溶微丸在压片过程中肠溶衣膜未发生破裂,表现出良好的耐酸性,与市售制剂的体外释放度相比f2相似因子值大于50,说明两种制剂体外释放行为相似。结论:本研究制备的兰索拉唑肠溶微丸型口崩片的耐酸性较好,与市售制剂相比体外释放相似性较高,可进一步放大生产。     

确定性筛选设计优化奥氮平片的处方和工艺

目的 研究奥氮平片处方和制备工艺。方法 用HPLC测定奥氮平片的奥氮平和有关物质含量,用光纤药物溶出度实时测定仪测定溶出曲线,用确定性筛选设计优化奥氮平片的处方和工艺。结果 微晶纤维素加入方式（内加或外加）和羟丙基纤维素用量对颗粒大小分布有显著影响,羟丙基纤维素用量和制粒搅拌速率对溶出曲线相似因子f₂有显著影响。经过优化得到的奥氮平片处方为奥氮平2.5%、乳糖78%、微晶纤维素10%（内加）、羟丙基纤维素4%、交联聚维酮5%、硬脂酸镁0.5%;制粒工艺参数：切割速度30 rps、搅拌速度3 rps、制粒时间5 min。结论 确定性筛选设计适用于奥氮平片处方和制备工艺的筛选和优化,根据确定性筛选设计确定的处方和制备工艺所制的奥氮平片,其溶出曲线与参比制剂相似,其含量均匀度和有关物质均符合中国药典2015年版标准。     

阿立哌唑口崩片的制备与质量评价

摘 要 目的：制备阿立哌唑口崩片,通过析因试验设计考察处方并评价其质量。方法: 本研究以原料药粒径（X₁,D90/um）、填充剂配比（X₂,%）、崩解剂用量（X₃,%）作为影响因素,以片剂硬度（Y₁,N）、崩解时限（Y₂,s）、药物溶出度（Y₃,%）作为评价指标,利用析因试验设计考察对阿立哌唑口崩片质量影响较为显著的处方因素,并最终确定最优处方;比较自制制剂与参比制剂在4种溶出介质中的溶出行为,并通过加速试验考察产品的稳定性。结果:通过析因方差分析结果显示：填充剂配比对片剂硬度影响较为显著（P<0.05）;崩解剂用量和填充剂用量配比对崩解时间具有显著影响（P<0.05）;原料药粒径对药物溶出度具有显著影响（P<0.05）。最终确定阿立哌唑口崩片的最优处方组成为：阿立哌唑原料药粒径D90控制在20~40 μm之间,填充剂甘露醇与微晶纤维素比例为2.5:1、崩解剂占片重5.0%,制备的片剂硬度高、崩解时限较短、药物溶出较快。与参比制剂的溶出相似,通过加速试验考察,有关物质无显著增加,质量符合要求。结论:阿立哌唑口崩片处方设计合理,制备工艺可行,质量可控。     

盐酸阿夫唑嗪口崩片的制备及体外溶出度影响因素考察

目的制备盐酸阿夫唑嗪口崩片,考察其体外溶出特性,并对影响其体外溶出度的因素进行考察。方法采用正交试验设计方案,以体外溶出度为考察指标,对盐酸阿夫唑嗪口崩片进行处方筛选,最后考察可能影响体外溶出度和崩解时限的因素。结果按优化处方制备的口崩片体外溶出度较好,崩解较快。结论制备的口崩片溶出度好,影响体外溶出度的主要因素为PVPP用量、PVP浓度及压力。     

D-最优混料试验设计法优化阿德福韦酯片处方

摘 要 目的：优化阿德福韦酯片处方,并考察其体外溶出度。方法: 以填充剂用量（X1,%）、崩解剂用量（X2,%）和黏合剂用量（X3,%）为影响因素,以脆碎度（Y1,%）、崩解时限（Y2,min）、阿德福韦酯30 min溶出度（Y3,%）为评价指标,采用D 最优混料试验设计法对阿德福韦酯片处方进行优化;采用f2相似因子法比较阿德福韦酯片仿制制剂和参比制剂的体外溶出行为相似性;通过高温、高湿、光照试验初步评价仿制制剂的稳定性。结果: 阿德福韦酯片的最优处方组成为：填充剂一水乳糖用量占片重67.0%、崩解剂交联羧甲基纤维素钠占片重8.0%,黏合剂预胶化淀粉占片重12.0%,制备的片剂脆碎度较低、崩解时限较短、药物溶出度高。阿德福韦酯片仿制制剂和参比制剂在4种溶出介质中的溶出相似因子f2均大于50。影响因素试验结果要求本品应防潮保存。结论: 通过D 最优混料试验设计法优化得到的阿德福韦酯片处方与参比制剂体外溶出一致性良好,制备工艺可行,能够满足制剂大生产的要求。     

尼莫地平自微乳化颗粒的研制及质量评价

摘 要 目的:制备尼莫地平固体自微乳化颗粒,并对其进行质量评价。方法: 通过综合考察不同处方比例的成型率、重分散性及体外溶出度,筛选尼莫地平固体自微乳化颗粒的最佳处方,并对最佳处方的粒径、Zeta电位、溶出度进行考察,同时用差示扫描量热法（DSC）、X-衍射考察尼莫地平在制剂存在状态。结果:最佳处方为尼莫地平-油酸乙酯-Tween 80-PEG400-糊精-乳糖-甘露醇的质量比为0.03∶0.2∶0.55∶0.25∶1∶1∶2,其自微乳化后平均粒径(28.8±0.71) nm,30 min溶出度达80.7%。结论:尼莫地平固体自微乳化颗粒制备简单,质量稳定,可提高药物溶出度。     

枸橼酸他莫昔芬片的制备及质量评价

目的 探索枸橼酸他莫昔芬片的处方和制备工艺,并对其进行质量评价。方法 通过考察填充剂比例、黏合剂浓度、崩解剂用量、润滑剂用量、颗粒大小和水分含量等,筛选最优处方比例及制备工艺。制备若干批枸橼酸他莫昔芬片（1 000片/批）,对颗粒休止角、药物晶型、片质量差异、硬度、崩解时限、含量等进行质量评价;同时,建立多条溶出曲线利用相似因子法评价自制片与参比制剂的相似性。结果 选用本处方和工艺条件制备的枸橼酸他莫昔芬片质量符合中国药典2015年版中的相关质量要求;4种溶出介质中溶出曲线的相似因子f₂值均>50。结论 枸橼酸他莫昔芬自制片与参比制剂具有体外溶出一致性。     

氯雷他定纳米混悬剂冻干口崩片的制备与质量评价

摘要：目的:制备氯雷他定纳米混悬剂冻干口崩片,评价其质量。方法:采用反溶剂沉淀-辅助超声技术法制备氯雷他定纳米混悬剂,并通过冷冻干燥工艺将其制备成口崩片,使用二因素三水平（32）析因设计优评估明胶浓度（X1）和甘露醇浓度（X2）对冻干口崩片的粒径大小（Y1）、崩解时限（Y2）、脆碎度（Y3）和5 min时药物溶出度（Y4）的影响,并得到氯雷他定纳米混悬剂冻干口崩片的最优处方组成;比较氯雷他定纳米混悬剂冻干口崩片在冻干前后的粒径分布,通过扫面电镜观察纳米混悬剂及其冻干口崩片的微观结构,对比氯雷他定纳米混悬剂冻干口崩片与氯雷他定口崩片的体外药物溶出速率。结果:经试验优化得到氯雷他定纳米混悬剂冻干口崩片的最佳处方为:明胶浓度为1.7%,甘露醇浓度为18.0%;冻干前后氯雷他定纳米混悬剂的粒径分布未发生显著变化;在扫面电镜下可以观察到氯雷他定纳米混悬剂呈不规则颗粒状分布,冻干口崩片呈多孔网状结构;制备的冻干口崩片与市售氯雷他定口崩片相比,崩解时限更短,药物溶出速度更快,在5 min内药物溶出度达到90%以上。结论:本研究将氯雷他定制备成纳米混悬剂冻干口崩片,处方设计合理,工艺可行,值得进一步研究。     

星点设计效应面法优化非洛地平自微乳给药系统

目的 设计非洛地平自微乳给药系统，并进行体外评价。方法 测定非洛地平的溶解度，考察油相与乳化剂的相容性，绘制伪三元相图，初步设计自微乳处方；运用星点设计效应面法优化自微乳处方；评价自乳化性能和体外溶出行为。结果 非洛地平自微乳处方：油相LABRAFIL M 1944CS为4.4 g，乳化剂Cremophor EL35为5.5 g，助乳化剂PEG400为1.1 g，非洛地平1.0 g；自乳化效率高，乳液澄明稳定，平均粒径为30.4 nm，PDI为0.16；水中溶出很快，5 min内平均溶出度>85%，30 min达99%，24 h后乳滴依然稳定。结论 星点设计-效应面法优化的非洛地平自微乳，自乳化性能高，乳液稳定，显著提高非洛地平的体外溶出度。     

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.