去氢骆驼蓬碱脂质体冻干剂粉的制备工艺优选

目的:制备含有不同冻干保护剂的N-三甲基壳聚糖(TMC)包衣去氢骆驼蓬碱脂质体(TMC-HM-LP)的冻干粉,并筛选其最佳制备工艺。方法:用"薄膜分散-pH梯度法"制备去氢骆驼蓬碱脂质体,并采用孵育包衣法、低温高速离心法和结合高效液相色谱(HPLC)定量方法测定其包衣脂质体的包封率;以其冻干粉的外观在冻干前和复溶后脂质体的粒径、包封率作为对比指标,优选出最佳的冻干工艺以及冻干保护剂的种类及比例。结果:以葡萄糖-乳糖-甘露醇(2:1:0.5)作为冻干保护剂,通过"分步预冻"的方法和-80℃冷冻干燥技术得到的TMC-HM-LP外观良好,冻干前后粒径和包封率变化较小。结论:采用冷冻干燥技术并结合冻干保护剂的优选,可显著提高包衣脂质体的稳定性。     

粉防己碱脂质体的制备及其稳定性研究

目的:比较粉防己碱脂质体2种制备方法。方法:采用硫酸铵梯度法和薄膜分散法制备粉防己碱脂质体,从渗漏率、粒径大小、磷脂含量3个方面进行稳定性比较,从包封率方面进行质量比较。结果:硫酸铵梯度法制备的粉防己碱脂质体包封率高达81.1%,且稳定性好;薄膜分散法包封率仅为32.9%,且稳定性欠佳。结论:硫酸铵梯度法较薄膜分散法制备粉防己碱脂质体更优。     

紫杉醇冻干脂质体的制备及含量稳定性

目的制备水化后粒径较小且分布较窄的,具有良好稳定性的紫杉醇冻干脂质体。方法以商品大豆磷脂为膜材,采用薄膜分散-微孔滤膜挤出(或高压均质)-冷冻干燥工艺制备冻干脂质体产品,采用HPLC和微柱离心-HPLC法测定冻干脂质体重建后的含量及包封率。并以加速和长期实验来证实该产品的稳定性。结果薄膜分散-微孔滤膜挤出-冷冻干燥工艺制备的紫杉醇冻干脂质体粒径均一,在130 nm左右,其对药物的包封率较高,可保证在90%以上,储存半年后紫杉醇的含量及包封率均未有降低。结论薄膜分散-微孔滤膜挤出-冷冻干燥工艺是制备紫杉醇脂质体的可工业化生产的方法。     

白术挥发油脂质体的制备及质量考察

目的制备白术挥发油脂质体并考察其性质。方法采用薄膜分散法制备白术挥发油脂质体,正交设计优化处方,低温高速离心法分离脂质体和游离药物,HPLC测定脂质体的包封率,并测定其zeta电位和粒径,考察其稳定性。结果白术挥发油脂质体包封率为62．7％,zeta电位为36．65mV,平均粒径为206．9nm。结论薄膜分散法制得的白术挥发油脂质体包封率高。粒径分布均一,稳定性较好。     

多烯紫杉醇脂质体的制备及其性质考察

目的：制备多烯紫杉醇冻干脂质体并对其性质进行考察。方法：本实验采用改善的薄膜分散法制备了多烯紫杉醇脂质体并将其冻干制成多烯紫杉醇冻干粉，通过粒径测定、ζ电位的测定、包封率的测定、稳定性的考察等研究了多烯紫杉醇冻干脂质体的性质。结果：通过在脂质材料中加入聚山梨酯80可以较好地提高药物在其中的溶解能力，提高脂质体的载药量。采用蔗糖和甘露醇混合使用作为冻干保护剂可以使脂质体冻干粉具有较好的成形性和复溶能力。测得冻干前后多烯紫杉醇脂质体的包封率分别为98，6％和95．3％，粒径分别为136和152nm，ζ电位分别为一21．3和一20．8mV。脂质体在葡萄糖输液中6h内含量和粒径均无明显变化，而包封率有下降的趋势。结论：本实验所制得的多烯紫杉醇脂质体粒径分布范围窄，包封率较高，是很有应用前景的一种脂质体制剂。     

前列地尔脂质体的制备及刺激性考察

目的 :制备前列地尔脂质体以减少其静脉注射的刺激性。方法 :采用逆相蒸发法制备前列地尔脂质体 ,用超滤膜测定脂质体的包封率及其释放、马尔文粒径仪测定平均粒径 ;并通过动物实验比较静脉注射的刺激性。结果 :前列地尔脂质体的包封率可达到 94 % ,超声后和高压匀质后的粒径为(732±s 35 )nm和 (6 7± 7)nm ,刺激性得到显著改善。结论 :前列地尔脂质体可以显著降低静脉注射引起的刺激性。     

大黄酚脂质体的制备工艺研究

目的:对大黄酚脂质体的处方和制备工艺进行研究,并评价其质量。方法:采用薄膜-超声分散法制备了大黄酚脂质体,并对制剂的包封率、形态学、粒径分布、稳定性等进行研究。结果:本研究制备的大黄酚脂质体处方为药脂比3∶30,脂材比1∶3,成膜温度为45℃,缓冲溶液pH为8.2,得到的脂质体粒径均匀,包封率达86.9%。结论:采用薄膜-超声分散法制备的大黄酚脂质体具有较高包封率和稳定性。     

多西他赛脂质体冻干粉的制备及质量评价

采用薄膜分散法结合冷冻干燥工艺制备多西他赛脂质体冻干品.采用正交试验,以包封率为指标优化处方,并考察了形态、粒径、包封率、体外释放和稳定性.结果表明,按优化处方制得的脂质体冻干品复溶后颗粒呈球形,平均粒径为(167.1±71.2)nm,平均包封率为(85.9±0.6)%;24h累积释放70.3%,释放曲线符合Weibull方程.多西他赛脂质体冻干品4℃放置3个月稳定性良好.     

尼美舒利脂质体的制备及质量评价初步研究

目的制备尼美舒利(NIM)脂质体,并进行质量评价。方法采用薄膜分散法制备NIM脂质体,并对其显微外观、包封率进行评价。结果薄膜分散法制备的NIM脂质体外形圆整、光滑、不粘连,包封率为(77.18±2.97)%。结论薄膜分散法制备的NIM脂质体包封率较高,达到了预期的目标。     

苦参碱脂质体的研制

目的制备苦参碱脂质体。方法采用薄膜分散法制备苦参碱脂质体,以包封率为考察指标,采用正交设计优化处方和制备工艺;并初步考察了其稳定性。结果优化处方与工艺所得脂质体形态均匀,粒径范围为200nm~600nm,包封率为48.5%。结论所制苦参碱脂质体包封率较高、稳定性良好。     

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.