星点设计-效应面法优化三七总皂苷生物黏附型缓释片处方

目的 通过星点设计-效应面优化法优化三七总皂苷生物黏附型缓释片处方.方法 以卡波姆971P和乳糖的用量为考察因素,以2、8、16、24 h的累积释放度为考察指标,采用二次多项式模型描述指标和两因素间的数学关系,根据模型绘制效应图,设定释药目标值,通过重叠等高线图确定优化处方,最后进行验证.结果 Rg1的累积释放度随卡波姆971P用量的增加而显著降低,随乳糖用量的增加而增加;确定了优化区域为:卡波姆971P用量为53～72 mg,乳糖用量为78～162 mg.结论 采用星点设计-效应面法,得到了三七总皂苷生物黏附型缓释片处方的优化模型,实现了缓释片的处方优化.     

星点设计-效应面法优化盐酸二甲双胍缓释片处方

目的 应用星点设计-效应面法优化盐酸二甲双胍缓释片的处方.方法 以HPMC K100M的用量和Carbopol 71GNF的用量为考察因素,以1,3,6和10 h的累积释放度为考察指标,采用多元线性回归和多元非线性回归拟合选择合适的模型,根据最佳模型绘制效应面图和等高线图,选择最佳处方并进行验证.采用相似因子对自研片和...     

星点设计-效应面法优化鱼腥草素钠缓释片的处方

目的 应用星点设计-效应面法优化鱼腥草素钠缓释片的处方.方法 以HPMC和EC的用量为考察因素,分别以鱼腥草素钠在1, 4, 8和12 h的累积释放度为指标,采用星点设计-效应面优化法,确定优化处方区域,并进行优化处方的验证分析. 结果最优处方区域为HPMC 42～62 mg和EC 5.8～6.6 mg,优化处方的考察...     

盐酸氯米帕明缓释片的制备及其体外释放度考察

目的:制备盐酸氯米帕明缓释片并考察其体外释放度。方法:以辅料羟丙基甲基纤维素(HPMC)、乳糖、可压性淀粉在处方中的含量为因素,体外释放度为指标,用正交试验优化处方并制备制剂,同时考察其体外释放度。结果:筛选最优处方为HPMC45mg、乳糖35mg、可压性淀粉40mg。所制制剂可持续24h释药,释药行为符合零级释放模型。结论:所制缓释片的处方合理,具有良好的缓释效果。     

星点设计-效应面法优化尼可地尔胃漂浮缓释片制剂处方

目的:应用星点设计-效应面法对尼可地尔胃漂浮缓释片进行处方优化。方法:采用粉末直接压片法,以制剂辅料中HPMC、十八醇和碳酸氢钠的用量为考察因素,以1,4,8 h的累积释放度和漂浮性能为评价指标,应用星点设计-效应面法优化制剂处方,并对胃漂浮缓释片释药机理做初步研究。结果:最佳制剂处方为:HPMC 60 mg、十八醇40 mg、碳酸氢钠30 mg;经处方验证,体外累积释放度的预测值与实测值偏差<5%,起漂时间<5 min,续漂时间>8 h;经Ritger-Peppas方程拟合,n=0.5357,提示该缓释片体外释放为非Fick扩散,具扩散与骨架溶蚀的双重机制。结论:应用星点设计-效应面法优选出了最佳制剂处方,按最佳制剂处方制备的尼可地尔胃漂浮缓释片具有良好的漂浮性能和缓释特性,制备方法简便。     

星点设计-效应面法优化盐酸普罗帕酮缓释片处方

目的采用星点设计-效应面法优化盐酸普罗帕酮缓释片的处方。方法以羟丙基甲基纤维素、乳糖的用量为考察因素,体外累积释放度为考察指标,选用星点设计-效应面法优化处方,并对结果进行验证。结果优化处方中羟丙基甲基纤维素和乳糖的用量分别为31.19%~32.16%,8.67%~14.7%,预测值与实测值的偏差均在6%以内。结论通过星点设计-效应面法建立的模型可用于盐酸普罗帕酮缓释片的优化,所建立的数学模型具有准确的预测性。     

阿普唑仑缓释片的处方筛选及体外释放度考察

目的:优选阿普唑仑缓释片处方,并对制剂进行体外释放度考察。方法:以羟丙基甲基纤维素(HPMC)、乙基纤维素、乳糖在处方中的用量百分比及HPMC的规格为考察因素,体外释放度为考察指标,经正交试验优化缓释片最佳处方,并对优化后处方所制制剂进行体外释放度考察。结果:优化处方中HPMC、乙基纤维素和乳糖用量百分比分别为30%、4%、15%,HPMC的规格为K4M;优化后所制制剂可持续释药24h,释药特性符合Higuchi方程。结论:所筛选的阿普唑仑缓释片处方合理并具有体外缓释性。     

星点设计-效应面法优化盐酸普萘洛尔择时释药片处方

摘要：目的:优化盐酸普萘洛尔择时释药片的处方。方法:采用干法压制包衣法制备盐酸普萘洛尔择时释药片,以释药时滞(Tlag)和8 h累积释药百分率为评价指标,以包衣中羟丙甲纤维素（HPMC）、微晶纤维素（MCC）、乳糖的用量为考察因素,采用星点设计-效应面法优化制剂处方,并进行处方验证。结果:最优处方为HPMC 85 mg,MCC 45 mg,乳糖20 mg。实测释药时滞为4.2 h,8 h累积释药百分率为87.0%。与预测值的偏差分别为4.8%和1.7%。结论:采用星点设计-效应面法优化出最优处方,所建立的数学模型预测性好,所得制剂具有良好的择时释药制剂特性。     

复方阿仑膦酸钠缓释片的制备及体外释放度考察

目的:制备复方阿仑膦酸钠缓释片并考察其体外释放度。方法:以羟丙基甲基纤维素(HPMC)、乙基纤维素(EC)、无水乳糖处方用量为因素,体外释放度为指标,用正交试验优化处方,以湿法制粒压片制备制剂,并考察其体外释放度。结果:筛选最优处方为HPMC 80mg、EC 20mg、无水乳糖20mg。所制制剂可持续12h释药,释放行为符合Higuchi方程。结论:所制缓释片的处方合理,具有良好的缓释效果。     

星点设计-响应面法优化盐酸罗沙替丁醋酸酯缓释片的处方

目的:优化盐酸罗沙替丁醋酸酯(ROX)缓释片的处方。方法:采用粉末直接压片法制备ROX缓释片,以1、4、8 h的体外累积释放度的综合指标为指标,以乳糖/微晶纤维素(MCC)(m/m)、乙基纤维素(EC)用量、羟丙基甲基纤维素(HPMC)用量为因素,采用星点设计-响应面法优化制剂处方,并进行验证。结果:最优处方为ROX 75 mg、乳糖45 mg、MCC 91 mg、EC 65 mg、HPMC 124 mg、微粉硅胶2 mg。所制缓释片1、4、8 h的体外累积释放度分别为(30.7±0.5)%、(65.8±0.7)%、(89.4±0.6)%,与预测值的相对误差分别为0.6%、0.8%、1.2%。结论:成功制得达到预期缓释效果的ROX缓释片。     

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.