球晶造粒法制备硝苯地平缓释微球

目的考察硝苯地平缓释微球的制备工艺及其体外释放度。方法以邻苯二甲酸羟丙甲纤维素酯(HP55)为载体材料,采用球晶造粒技术制备硝苯地平缓释微球。考察硝苯地平微球的粒径、形态、载药量、包封率及体外释放度。结果所得微球外观圆整度好,粒径分布在70~150μm,载药量为18.91%,包封率为94.95%。结论该法可用于硝苯地平缓释微球的制备。     

载环孢素A海藻酸钙-壳聚糖微球的制备及体外释放特性

目的:针对角膜移植术后免疫抑制治疗需求,制备眼部局部给药的小粒径载环孢素A缓释微球,并进行体外释放考察。方法:以海藻酸钠、壳聚糖为载体材料,采用静电液滴工艺,通过向制备体系添加表面活性剂,制备小粒径载环孢素A微球,设计正交试验优化处方工艺,扫描电镜观察微球表面形态,动态透析法考察微球的体外释放特性。结果:所制微球形态良好,粒径分布窄,平均粒径为(12.4±0.8)μm,包封率为(82.8±1.8)%,载药量为(50.1±1.2)%,体外释放行为用Higuchi方程拟合效果最好。结论:采用静电液滴工艺,通过减小制备体系的表面张力,制备了球形度优良、粒径小、包封率和载药量较高的载环孢素A的壳聚糖-海藻酸盐缓释微球,所得制剂的体外释药规律服从扩散机制。     

载药蒙脱石/丙烯酸树脂微球的制备与体外释放性能的研究

目的以丙烯酸树脂为膜材制备载药蒙脱石/丙烯酸树脂微球并考察其体外释放性能。方法以盐酸倍他洛尔为模型药物,采用O/O溶剂挥发法制备蒙脱石载药微球,通过正交实验设计,考察柠檬酸三乙酯及甘油用量、乳化剂与膜材比例及用量、内外相体积比等因素对微球载药量、包封率、体外释放性能的影响,采用扫描电镜对其外观形态进行表征。结果所得微球外观圆整,粒径分布较均匀,平均粒径为20.7μm,平均载药量为14.31%±0.47%,平均包封率为94.35%±1.01%。结论该法制备载药蒙脱石丙烯酸树脂微球是可行的,体外释放研究表明微球具有一定的缓释作用。     

替莫唑胺乳酸-羟基乙酸共聚物微球的制备及表征

采用乳化-溶剂挥发法制备替莫唑胺微球,考察了制备工艺中影响微球粒径、载药量和包封率的主要因素,筛选处方工艺.按优化工艺制得的微球形态圆整,表面光滑,平均粒径62.2μm,载药量7.5%,包封率83.5%,体外试验表明该载药微球有明显的缓释效果.     

阿立哌唑缓释微球的工艺优化及体内药动学研究

目的:制备阿立哌唑缓释微球,使用星点设计-效应面法优化工艺,并对其体内血药浓度进行分析。方法:采用乳化溶剂挥发法制备阿立哌唑微球;以油相二氯甲烷体积、水相聚乙烯醇质量分数及乳化转速为自变量,以微球的平均粒径、跨距、载药量、包封率、产率及突释量为因变量,对制备工艺进行优化,并对优化后的工艺进行验证。采用HPLC法测定家兔血浆中药物浓度。结果:最佳工艺为二氯甲烷体积1.62mL,聚乙烯醇质量分数1.91%,乳化转速2 161 r.min-1;按优化工艺制备的微球外观圆整、流动性好;平均粒径为41.54μm,跨距为1.01,载药量为18.82%,包封率为75.39%,产率为85.17%,突释为1.68%。自制微球制剂在家兔体内d 1有少量的突释,d 5～d 20维持较稳定的血药浓度,缓慢释放,之后浓度开始下降。结论:所优化的制备工艺重现性好,简单易行;星点设计-效应面法优化微球制备工艺预测性良好,所制备的微球具有较好的体外缓释特性;阿立哌唑缓释微球在家兔体内缓慢释放,该释药行为达到了预期的目的。     

利培酮长效注射微球的制备及体外释放的研究

目的：制备利培酮长效注射微球并考察其体外释放行为。方法：使用乳酸-羟基乙酸共聚物（PLGA）为材料,采用乳化-溶剂挥发法制备利培酮微球,观察微球的形态及粒径,测定微球的载药量和包封率,考察微球的体外释放情况。结果：利培酮微球表面圆整,粒径集中在40～80μm之间。微球的包封率较高,达到80％以上,以低分子量PLGA（50：50）制备的微球,体外突释很高达到40％以上;以高分子量PLGA（75：25）制备的微球,在高载药量时突释较小,可持续释放达3周以上。结论：以高分子量PLGA制备的高载药量的利培酮微球,体外突释较小可缓释达3周以上。     

布比卡因缓释微球的制备及体外释药特性评价

目的研究布比卡因缓释微球制备方法并对其体外释药特性进行评价。方法采用紫外分光光度法测定布比卡因微球载药量、包封率;采用HPLC法测定微球体外释放;通过正交设计优选微球制备工艺;以乳酸羟基乙酸共聚物为载体,使用乳化溶剂挥发法制备布比卡因微球;用扫描电镜观察所得微球的粒径和形态;通过体外释药实验考察布比卡因乳酸羟基乙酸共聚物微球的缓释作用。结果微球载药量、包封率和体外释放的测定方法符合方法学要求;按照优选处方制备所得的微球为圆整球体,表面多孔,呈蜂窝状,粒径50~100μm之间的微球占80%;体外释放符合Ritger-Peppas方程,t1/2=242.05 h。结论乳化溶剂挥发法适用于布比卡因乳酸羟基乙酸共聚物微球的制备,所制得的微球形态圆整,在体外具有明显缓释作用。     

他克莫司纳米微球的制备及其体外释药性能

目的采用甲氧基聚乙二醇-聚乳酸聚合物（PEG—PLA）制备他克莫司微球（PPT），研究其体外释药特性。方法考察PPT的载药量、包封率、粒径大小、粒径分布和药物体外释放实验。结果PPT的制备工艺稳定、重复性好，微球外形圆整，表面光滑，分布均匀，平均粒径为（545．1±0．9）nm，平均载药量为（18．90±3．22）％，平均包封率为（25．0±1．6）％，35d的药物累积释放率为67．21％。结论他克莫司微球缓释时间长达35d，能够满足临床治疗的要求。     

利福平丝素蛋白载药微球的制备及性能研究

目的通过测定利福平丝素蛋白微球的载药量、包封率及释放度,考察乳化转速、有机溶剂与丝素蛋白溶液比例,对微球的制备方法进行优化,筛选微球的最佳制备方法。方法采用乳化法制备利福平丝素蛋白微球,以不同转速、有机溶剂与丝素蛋白溶液不同比例分别制备利福平丝素蛋白微球,采用扫描电镜观察微球的形态,用紫外分光光度法测定微球的载药量、包封率及释放度,以形态、载药量、包封率及释放度为指标,筛选微球的最佳制备方法。在此基础上,采用最佳处方制备3批利福平丝素蛋白微球,对微球的形态、粒径、包封率、载药量和释放度进行考察。结果有机溶剂与丝素蛋白溶液体积比为4∶1、转速为200 r·min^-1时所得利福平丝素微球形态均匀,近似球形,载药量和包封率较高,所得载药微球有较好的缓释作用。以最佳处方制得微球载药量为66.1%±0.87%,包封率为87.80%±2.23%。结论有机溶剂与丝素蛋白溶液体积比为4∶1、转速为200 r·min^-1时载药量、包封率和释放度较好,故选择此处方为利福平丝素蛋白微球的最佳制备处方。     

阿司匹林缓释微球的制备及其体外释药性能研究

目的:制备阿司匹林缓释微球,并考察其体外释药性能。方法:采用改良的乳化溶剂挥发法,以聚乳酸-羟基乙酸共聚物(PLGA)为载体材料、载药量和包封率为指标,固定PLGA为100 mg正交设计试验优化阿司匹林缓释微球的阿司匹林用量、外水相体积、丙酮-二氯甲烷体积比和聚乙烯醇(PVA)浓度,对最优处方所制微球进行验证和体外释放度考察。倒置显微镜和电子显微镜下观察微球表面形态,激光粒度分析仪考察微球粒径。结果:PLGA为100 mg时的最优处方:阿司匹林用量为20 mg、外水相体积为150 ml、丙酮-二氯甲烷体积比为1∶1、PVA浓度为1 mg/100 ml;所制微球的平均粒径为139.95μm,电镜下微球表面光滑圆整,载药量为8.6%,包封率为33%,240 h体外累积释放度为85.56%。结论:成功制得具有明显缓释作用的阿司匹林缓释微球。     

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.