康普瑞丁脂质体的研制及评价

目的 研究康普瑞丁(CA4)脂质体的处方,并评价其性质.方法 采用乙醚注入法制备CA4脂质体,以正交设计优化最佳处方,测定脂质体的形态和粒径,用HPLC法测定脂质体中CA4的包封率,并考察脂质体的体外释放规律.结果 制备的脂质体平均粒径为16.04 nm,最佳工艺处方为磷脂与胆固醇比为6:1,附加剂P、A、B的用量分别为2%、2%、20%.所制3批脂质体的平均包封率为92.78%,体外释药规律符合Higuchi方程.结论 乙醚注入法制备CA4脂质体可行.     

鬼臼毒素衍生物脂质体处方和制备工艺优选

目的:优选鬼臼毒素衍生物5-氟尿嘧啶乙酸鬼臼酯(5-FPE)脂质体处方和制备工艺。方法:采用薄膜超声分散法制备5-FPE脂质体,以包封率为指标通过正交试验法优选制备处方和工艺,并考察制备的脂质体的包封率、载药量、形态、粒径分布、Zeta电位及在25、4℃条件下存放10d后的体外稳定性。结果:确定了最优处方和工艺,以此制备的3批脂质体的平均包封率为66.45%,平均载药量为7.97%,粒径均值为284.7nm,平均Zeta电位为—22.15mV;脂质体存放10d后包封率下降,但在4℃条件下存放的脂质体的包封率变化比25℃的更小。结论:以优选处方和工艺制备5-FPE脂质体具有可行性,可为进一步的制剂研究提供基础。     

硝酸咪康唑脂质体的制备工艺研究

目的:探讨硝酸咪康唑脂质体的制备工艺.方法:以包封率和载药量为指标,应用正交试验法优选最佳制备工艺.结果:最佳工艺处方为乙醇注入法,药脂比3%(w/w),磷脂与胆同醇的摩尔比为80:20,缓冲液pH7.4.制备的脂质体包封率为75.54%,平均粒径为222.3 nm,zeta电位为-0.31mV.结论:乙醇注入法制备硝酸咪康唑脂质体包封率高.制备工艺合理、可行.     

改良自乳化-溶剂扩散法制备甲基莲心碱纳米粒的研究

目的制备甲基莲心碱纳米粒(NEF-NP),并采用正交试验设计对甲基莲心碱纳米粒制备工艺进行优化。方法以包封率和载药量为评价指标,采用聚乳酸-羟基乙酸共聚物(PLGA)为载体,丙酮-无水乙醇为有机溶剂,通过正交设计优化改良自乳化-溶剂扩散法制备载NEF的PLGA载药纳米粒的处方工艺。结果优化的最佳处方工艺为:PLGA的浓度为20 mg.mL-1,NEF的投药量为3.3 mg,PVA浓度为1.0%,水相与有机相的体积比为8∶1。最佳条件下制得的纳米粒平均包封率达(70.35±1.16)%,载药量(2.33±1.08)%,平均粒径为(213.5±2.7)nm。结论最佳处方工艺制备的NEF-PLGA纳米粒具有较高的包封率、载药量和较小的粒径。     

Box-Behnken效应面法优化制备主动载药盐酸小檗碱脂质体

目的采用Box-Behnken效应面法筛选最佳处方,制备盐酸小檗碱脂质体。方法采用薄膜分散-p H梯度法制备脂质体,分别以磷脂与胆固醇质量比、脂药质量比、外水相p H值、孵化温度为考察对象,以包封率、粒径和载药量为评价指标,采用4因素3水平Box-Behnken效应面设计法筛选盐酸小檗碱脂质体的最佳处方。采用阳离子交换树脂微柱离心法测定包封率,动态激光散射法测定脂质体的粒径,并采用透射电镜观察制得的脂质体形态。结果最优处方工艺条件为磷脂与胆固醇质量比为3.38∶1,脂药质量比为22∶1,外水相p H为6.88,孵化温度为59℃。以最优处方制备的盐酸小檗碱脂质体平均粒径、包封率、载药量与预测值偏差较小。结论采用Box-Behnken效应面法优化盐酸小檗碱脂质体工艺处方是可行的。     

PVP包覆β-榄香烯脂质体的处方与工艺优化

目的:考察3种不同相对分子质量的聚乙烯毗咯烷酮(PVP)包覆的β-榄香烯脂质体的包封率,确定最终处方。方法:采用正交设计优化处方与制备工艺;采用乙醇注入法制备不同相对分子质量PVP包覆的β-揽香烯脂质体;采用微柱离心-气相色谱法测定脂质体包封率。结果:正交试验结果证明利用1%PVP-k30包覆,载药量为0．5%,磷脂用量为6%,磷脂与胆固醇质量比例为6:1为最佳处方。结论:脂质体用PVP包覆后包封率为(97．19±0．27)%,与普通脂质体相比未见明显变化,粒径则略有增加。     

透明质酸介导姜黄素靶向脂质体的制备及质量评价

目的 制备透明质酸-姜黄素脂质体(HA-CUR-L),并考察其包封率及质量评价.方法 采用逆相蒸发法制备HA-CUR-L,测定其包封率、HA结合率、形态分布、粒径及体外释放度.结果 脂质体平均包封率为88.75％,HA结合率为71.69％;脂质体平均粒径为160 nm;36 h后,累计释药量为82.26％.结论 选用逆相蒸发法制备HA-CUR-L,处方合理,工艺简便可行,包封率高.     

硫酸铵梯度法制备莫西沙星脂质体的工艺研究

目的 制备具有较高包封率和载药量且体外放置稳定的莫西沙星脂质体。方法 采用硫酸铵梯度法制备包载莫西沙星的脂质体,以粒径及其分布和包封率、载药量为指标对处方和工艺进行优化。结果 最佳制备条件为：空白脂质体中硫酸铵质量浓度70 mg/mL、磷脂质量浓度50 mg/mL、脂质体粒径120 nm左右、透析时间5 h、载药时药脂比2∶3、孵育温度40 ℃、孵育时间30 min。制备得到的莫西沙星脂质体粒径为（143.00±3.98）nm,包封率为（74.56±3.21）%,载药量为（26.39±1.88）%。结论 硫酸铵梯度法制备的莫西沙星脂质体包封率较高,粒径均一,室温放置稳定性良好。     

胸腺五肽脂质体的研制

目的:制备胸腺五肽脂质体并进行质量评价。方法:采用复乳法制备胸腺五肽脂质体,以聚乳酸-羟基乙酸共聚物(PLGA)及卵磷脂为成球材料、以胸腺五肽为主药制备脂质体。以明胶浓度、PLGA浓度和卵磷脂浓度为考察因素,以包封率和载药量为考察指标设计L(934)正交试验优化基质处方并进行验证试验。通过测定优化处方所制脂质体粒径、包封率、体外累积释放百分率等评价脂质体质量。结果:优化基质处方为明胶、PLGA和卵磷脂浓度分别为100、200、100mg.mL-1。所制脂质体形态完整,平均粒径为(9.03±0.83)μm,载药量与包封率分别为(1.81±0.03)与(74.4±1.4),20d的累积释药百分率达90以上。结论:所制胸腺五肽脂质体工艺简单、重现性好,包封率和载药量高,具有显著的缓释作用。     

响应面设计优化超临界CO_2法制备盐酸小檗碱脂质体的处方工艺

目的采用中心复合设计实验优化超临界CO2法制备盐酸小檗碱脂质体的处方工艺。方法考察药脂质量比和磷脂质量浓度对盐酸小檗碱脂质体包封率的影响,采用中心复合设计实验对超临界制备盐酸小檗碱处方工艺进行优化,并利用响应曲面法进行优化分析。结果最优的工艺条件为:药脂质量比为13.2∶60,磷脂质量浓度为30 g.L-1,理论包封率为73.30%,载药量为15.98%。在此条件下的实际包封率为(72.15±1.9)%,载药量为15.74%,接近理论预测值。结论作者研究的超临界CO2法制备盐酸小檗碱脂质体,实现了包封率与载药量的最佳组合,且工艺简单,适合工业生产。     

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.

     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

Glycofection: The Ubiquitous Roles of Sugar Bound on Glycoplexes

Glycofection (transfection by using sugar-substituted polylysine) was assessed in order to provide an alternative to viral vectors for the transfer of genes into vascular smooth muscle cells. A rabbit vascular smooth muscle cell line (Rb-1 cells) was selectively transfected by using glycoplexes (glycosylated polylysine/pSV2LUC complexes) in the presence of 10 mu M of the fusogenic peptide GALA. A sugar-specific transfection was obtained when the glycofection was conducted for 1 h with glycoplexes containing either alpha Gal, alpha -Glc, alpha -GalNAc, beta -GlcNAc, or beta -GalNAc residues. The gene expression was high after transfection, with glycoplexes bearing alpha Gal, alpha -GalNAc, or beta -GalNAc residues that were weakly internalized, and low with glycoplexes carrying Lact or Rha residues that were well taken up by cells. These results suggest that 1) glycofection can be a good approach for a selective transfer of genes intovascular smooth muscle cells, 2) an efficient uptake of the glycoplexes is not the unique limiting step for an efficient transfection, and 3) the sugar-dependent trafficking of the glycoplexes inside the cells may account for the transfection efficiency.     

直肠癌下切缘病理组织学分析

目的探讨直肠癌逆向浸润与下切缘的安全距离的关系。方法对36例直肠癌Miles手术和Dixon手术后标本的肿瘤下缘1.0cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查,观察直肠癌逆向浸润或转移的距离。结果36例直肠癌标本距癌肿下缘1.0 cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查均为阴性,结论直肠癌远恻逆向浸润或转移未见超过1.0cm,因此认为保肛手术时切除肿瘤远侧肠管(包括系膜)2.0cm是安全的。