复方黄连肠炎宁胶囊定性定量标准研究

目的建立复方黄连肠炎宁胶囊的质量标准。方法采用薄层色谱法对该制剂中黄连、黄芪、地榆、补骨脂进行定性鉴别;采用高效液相色谱法测定复方黄连肠炎宁胶囊中盐酸小檗碱的含量。结果薄层色谱斑点清晰、分离度好,专属性强,盐酸小檗碱在0.420 0~3.502 5μg线性关系良好,平均回收率为99.8%,RSD=0.2%(n=6)。结论所建立的方法简便可靠,重复性好,可用于复方黄连肠炎宁胶囊的质量控制。     

RP-HPLC法测定复方明目汤中盐酸小檗碱的含量

目的建立测定复方明目汤中盐酸小檗碱含量的高效液相色谱法。方法色谱柱:Hypersil C18柱(250 mm×4.6 mm,5μm),流动相:乙腈-0.05 mol/L磷酸二氢钾溶液(45∶55),流速:1.0 mL/min,检测波长:265 nm。结果盐酸小檗碱的线性范围11.24~56.20μg/mL,r=0.999 9。平均回收率97.86%;RSD=1.42%。结论该法测定复方明目汤中盐酸小檗碱含量,操作简单,重复性好,精密度高。     

黄地安消胶囊的质量控制方法研究

目的:建立黄地安消胶囊质量控制的方法.方法:采用薄层色谱法(TLC)对黄地安消胶囊中的黄连、麦冬、葛根、枇杷叶进行定性鉴别研究;采用高效液相色谱法(HPLC)对黄地安消胶囊中君药黄连的活性成分盐酸小檗碱进行含量测定,色谱条件:Agilent Eclipse Plus C18色谱柱(4.6 mm×250 mm,5μm),流动相:乙腈-0.05 mol·L-1磷酸二氢钾(30:70),流速:1 mL· min-1,柱温:30℃,检测波长:345 nm.结果:薄层色谱鉴别斑点清晰,易于鉴别;采用HPLC法对黄地安消胶囊中的盐酸小檗碱进行含量测定,盐酸小檗碱在0.235～3.760 μ g范围内呈良好的线性关系,r=0.9999;平均加样回收率为99.84％,RSD=0.27％.结论:定性鉴别和含量测定方法操作简单,重现性、精密度及稳定性均良好,可用作黄地安消胶囊的质量控制研究方法.     

提高肠得安胶囊质量标准的研究

目的优化肠得安胶囊的质量标准。方法对原标准中薄层色谱鉴别黄柏、大黄和厚朴3味药的鉴别项进行了优化,并增加了甘草、乌药和芍药的薄层鉴别;建立了HPLC法测定处方中黄柏的盐酸小檗碱含量,色谱柱:Agilent Zorbax XDB C18(150mm×4.6mm,5μm);检测波长:345nm。结果各薄层色谱鉴别斑点清晰、分离好,阴性样品皆无干扰;含量测定盐酸小檗碱质量浓度在0.84~8.40μg·mL-1范围内呈良好的线性关系(r=0.999 9);平均加样回收率为97.3%,RSD值为0.86%(n=9)。结论所用定性、定量方法准确可靠,且能有效控制肠得安胶囊的质量。     

HPLC测定连栀矾溶液中表小檗碱、黄连碱、巴马汀和盐酸小檗碱的含量

目的:建立快速测定连栀矾溶液中表小檗碱、黄连碱、巴马汀和盐酸小檗碱含量的HPLC方法。方法:色谱柱为Chromstar TM C18色谱柱(4.6 mm×250 mm,5μm);流动相为乙腈-含0.1%三乙胺和0.1%甲酸的水溶液(30:70,V/V);检测波长345 nm,柱温30℃,流速0.8 m L﹒min-1。进样量20μL。结果:连栀矾溶液样品中表小檗碱、黄连碱、巴马汀和盐酸小檗碱在12 min内达到分离,峰形尖锐对称。盐酸小檗碱在2.82~44.91μg﹒m L-1范围内线性关系良好,平均加样回收率为97.95%。七批次连栀矾溶液中表小檗碱、黄连碱、巴马汀和盐酸小檗碱含量以盐酸小檗碱计,分别为0.126±0.019,0.167±0.029,0.140±0.018和0.618±0.079 mg﹒m L-1。结论:建立的HPLC方法高效、准确,经济,精密度好,灵敏度高,可用于连栀矾溶液中表小檗碱、黄连碱、巴马汀和盐酸小檗碱的同时快速测定分析。     

高效液相色谱法同时测定芩连片中巴马汀、小檗碱、黄芩苷、连翘苷的含量

目的建立高效液相色谱法同时测定芩连片中巴马汀(以盐酸巴马汀计)、小檗碱(以盐酸小檗碱计)、黄芩苷、连翘苷的含量。方法色谱柱为Gemini NX C_(18)(250 mm×4.6 mm,5μm);流动相为乙腈-甲醇-0.2%磷酸水溶液(23:5:72);流速:1.0 m L·min~(-1);检测波长:270 nm;柱温:35℃。结果盐酸巴马汀、盐酸小檗碱、黄芩苷、连翘苷浓度分别在0.420~4.200、2.940~29.40、2.590~25.90、0.370~3.700μg·m L~(-1)范围内与峰面积呈良好的线性关系,平均回收率(n=6)分别为101.3%、99.6%、100.2%、99.6%,RSD分别为1.7%、1.8%、2.0%、0.9%。结论该方法简便、准确、重复性好,可用于芩连片的质量控制。     

HPLC法测定玛木然止泻胶囊中盐酸小檗碱与没食子酸的含量

目的采用高效液相色谱法测定玛木然止泻胶囊中盐酸小檗碱和没食子酸的含量。方法色谱柱为Ecosil C18色谱柱(250mm×4.6mm,5μm)。盐酸小檗碱流动相为乙腈-0.05mol·L~(-1)磷酸二氢钾溶液(30∶70),检测波长为345nm,流速为1.0mL·min~(-1);没食子酸流动相为甲醇-2mL·L~(-1)磷酸溶液梯度洗脱,检测波长为270nm,流速为1.0mL·min~(-1)。结果盐酸小檗碱和没食子酸分别在0.211~2.109(r=0.999 1)及0.207~2.071μg·mL~(-1)(r=0.999 6)范围内线性关系良好;平均加样回收率分别为98.20%(RSD=2.20%)和102.52%(RSD=1.28%)。结论该方法准确、简便、重复性好,可用于玛木然止泻胶囊的质量控制。     

速效止泻胶囊定性定量检测方法研究

目的:建立速效止泻胶囊的定性定量检测方法。方法:采用TLC法鉴别速效止泻胶囊中盐酸小檗碱和拳参;采用HPLC法测定处方中盐酸小檗碱含量及拳参中绿原酸含量。盐酸小檗碱色谱条件:依利特Hypersil ODS2(4.6 mm×250 mm,5μm)色谱柱,以乙腈-0.05 mol·L-1磷酸二氢钾溶液-三乙胺(40∶60∶0.1)为流动相,流速1 mL·min-1,紫外检测波长346 nm,柱温为30℃;绿原酸色谱条件:依利特Hypersil ODS2(4.6 mm×250 mm,5μm)色谱柱,以乙腈-0.01 mol·L-1磷酸二氢钾溶液-三乙胺-磷酸(7∶93∶0.4∶0.3)为流动相,流速1 mL·min-1,紫外检测波长327 nm,柱温为30℃。结果:盐酸小檗碱和拳参薄层色谱定性鉴别特征明显;盐酸小檗碱与绿原酸含量测定,分别在2.0～6.0μg(r=0.9992)和0.1～1.8μg(r=0.9999)线性关系良好;平均回收率(n=6)分别为99.2%和102.3%,RSD分别为0.77%和1.3%。结论:本法可准确地定性、定量,有效地控制速效止泻胶囊的质量。     

复方蒲芩胶囊含量测定方法的改进

目的:改进复方蒲芩胶囊的含量测定方法。方法:采用HPLC法同时测定复方蒲芩胶囊中黄芩苷和盐酸小檗碱的含量。色谱柱为Diamonsil C18(4.6 mm×200 mm,5μm),以乙腈-0.05 mol.L-1磷酸二氢钠溶液(29∶71)(用磷酸调节pH值至3.0)为流动相,检测波长为280 nm。结果:黄芩苷和盐酸小檗碱的线性范围分别为0.056 57～0.848 6μg(r=0.999 9)和0.254 9～3.823 5μg(r=0.999 9);平均回收率分别为98.0%(RSD=2.2%),97.9%(RSD=0.97%)。结论:方法简便、准确,重复性好,可用于复方蒲芩胶囊质量控制。     

反相高效液相色谱法测定肠激安胶囊中芍药苷、盐酸小檗碱和盐酸巴马汀含量

目的:建立肠激安胶囊中芍药苷、盐酸小檗碱和盐酸巴马汀的反相高效液相色谱(RP-HPLC)含量测定方法,进一步提升肠激安胶囊的质量标准。方法:采用Agilent ZORBAX SB-C18色谱柱(4.6 mm×150 mm,5μm),以乙腈-0.4%磷酸溶液为流动相进行梯度洗脱,流速0.8 m L·min-1,检测波长230 nm,柱温30℃,测定肠激安制剂中芍药苷、盐酸小檗碱和盐酸巴马汀的含量。结果:芍药苷、盐酸小檗碱和盐酸巴马汀分离度良好,阴性溶液无干扰;芍药苷、盐酸小檗碱质量浓度在2.0~200.1μg·m L-1范围内线性关系良好,盐酸巴马汀质量浓度在2.0~200.2μg·m L-1范围内线性关系良好;3批次肠激安胶囊中芍药苷的含量分别为2.034 5、2.033 2、2.029 8 mg·g-1,RSD为0.12%;盐酸小檗碱的含量分别为5.471 2、5.470 1、5.474 2 mg·g-1,RSD为0.04%,盐酸巴马汀的含量分别为1.260 2、1.248 9、1.275 2 mg·g-1,RSD为1.05%。结论:该方法可同步检测肠激安制剂中芍药苷、盐酸巴马汀和盐酸小檗碱的含量,精密度、稳定性和重复性良好;肠激安制剂中芍药苷、盐酸小檗碱和盐酸巴马汀的含量稳定可控。     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.