碘甘油联合曲安奈德口腔软膏治疗口腔溃疡的临床研究

目的 建立同时测定枣仁安神胶囊中五味子醇甲、五味子醇乙、隐丹参酮、丹参酮I、丹参酮II_A、五味子乙素的方法,为枣仁安神胶囊的质量控制提供科学的方法。方法 采用HPLC法,选用Thermo 120Å-C₁₈色谱柱（250 mm×4.6 mm,5 μm）;以乙腈-0.1%冰醋酸水溶液为流动相梯度洗脱,对枣仁安神胶囊中6种主要指标性成分的含量进行同时分析测定;检测波长：五味子醇甲、五味子醇乙、五味子乙素为250 nm,隐丹参酮、丹参酮I、丹参酮II_A为270 nm;体积流量1.0 mL/min,柱温为30℃。结果 五味子醇甲在4.7～3 153.6 ng（r=0.999 9）、五味子醇乙在7.864～314.500 ng（r=0.999 9）,隐丹参酮在14.4～1 256.9 ng（r=0.999 9）、丹参酮I在15.1～1 103.8 ng（r=0.999 9）、丹参酮II_A在15.3～1 532.0 ng（r=0.999 9）、五味子乙素在6.134～204.500 ng（r=0.999 9）内呈良好的线性关系。平均加样回收率分别为五味子醇甲为100.4%、五味子醇乙为98.7%、隐丹参酮为99.4%、丹参酮I为100.0%、丹参酮II_A为99.3%、五味子乙素100.2%,RSD分别为1.4%、2.7%、2.2%、2.2%、2.5%、2.1%;8批样品中各指标成分的质量分数分别为五味子醇甲1.545 7～1.909 9 mg/g、五味子醇乙0.129 8～0.235 1 mg/g、隐丹参酮0.508 4～0.523 4 mg/g、丹参酮I 0.111 7～0.122 3 mg/g、丹参酮II_A 0.755 8～0.874 4 mg/g、五味子乙素0.120 2～0.190 1 mg/g。结论 建立的含量测定分析方法灵敏度高、专属性强,可很好地控制枣仁安神胶囊质量。     

HPLC同时测定护肝片中5种成分的含量

摘 要 目的：建立HPLC法同时测定护肝片中腺苷、五味子醇甲、五味子酯甲、五味子甲素和五味子乙素的含量。方法: 采用Agilent Eclipse XDB色谱柱（250 mm×4.6 mm,5 μm）,流动相为乙腈-0.7%磷酸溶液,梯度洗脱,流速为0.80 ml·min^-1,0～14 min检测波长为260 nm,14～58 min检测波长为250 nm,柱温为30℃,进样量为10 μl。结果: 腺苷、五味子醇甲、五味子酯甲、五味子甲素和五味子乙素的线性范围分别为2.35～47.00 μg·mL^-1（r=0.999 8）、14.90～297.00 μg·mL^-1（r=1.000 0)、3.46～69.20 μg·mL^-1（r=0.999 9）、4.00～80.10 μg·mL^-1（r=1.000 0）、3.42～68.30 μg·mL^-1（r=0.999 9）。5种成分的平均回收率均不低于98％。结论:本方法简便、准确、重复性好,可用于护肝片中腺苷、五味子醇甲、五味子酯甲、五味子甲素和五味子乙素的含量测定。     

HPLC同时测定瑞香狼毒中瑞香素、伞形花内酯和东莨菪内酯的含量

目的 建立HPLC同时测定瑞香狼毒中瑞香素、伞形花内酯和东莨菪内酯含量的方法。方法 样品经无水乙醇回流。采用Synergi 4u Polar-RP 80R柱（4.6 mm×250 mm,5 μm）,流动相为甲醇-1%冰醋酸溶液,等度洗脱,流速：1.0 mL·min^-1,检测波长：324 nm,柱温：30℃。结果 瑞香素在0.012~0.250 μg（r=0.999 9）、伞形花内酯在0.149~2.981 μg（r=0.999 9）、东莨菪内酯在0.012~0.239 μg（r=0.999 9）均呈良好的线性关系;瑞香素、伞形花内酯和东莨菪内酯的加样回收率分别为99.0%（RSD=0.94%）,98.7%（RSD=0.77%）和98.3%（RSD=1.16%）。结论 3种香豆素成分在35 min内达到基线分离,该方法分析时间短、稳定性和回收率良好,对瑞香狼毒药材的质量控制具有一定的参考价值。     

HPLC测定肾炎宁片中大黄酸、大黄素、大黄酚及雷公藤甲素的含量

目的 建立HPLC测定肾炎宁片中大黄酸、大黄素、大黄酚及雷公藤甲素的含量。方法 大黄酸、大黄素、大黄酚的测定采用流动相为甲醇-0.1%磷酸（70∶30）,检测波长为254 nm;雷公藤甲素采用流动相为乙腈-水（25∶75）,检测波长为220 nm;两者均采用Lichrospher-C₁₈柱（4.6 mm×250 mm,5 mm）,流速均为1.0 ml·min^-1。结果 大黄酸、大黄素、大黄酚以及雷公藤甲素分别在1.83~14.64 μg·ml^-1（r=0.999 9）,2.895~23.16 μg·ml^-1（r=0.999 8）,7.625~61.00 μg·ml^-1 （r=0.999 8）以及1.52~24.32 μg·ml^-1（r=0.999 6）内与峰面积呈良好的线性关系,大黄酸平均回收率为103.2%,RSD=1.73% （n=9）;大黄素平均回收率为98.6%,RSD=3.94%（n=9）;大黄酚平均回收率为98.3%,RSD=2.54%（n=9）;雷公藤甲素平均回收率为99.61%,RSD=2.83%（n=9）。结论 本方法准确、可靠、专属性强,可作为该制剂的定量控制方法。     

养阴镇静丸质量标准提高研究

目的 修订并提高养阴镇静丸的质量标准。方法 采用显微鉴别法对处方中的五味子、珍珠母、朱砂、茯苓进行定性鉴别。采用高效液相色谱法测定五味子中五味子醇甲的含量。结果 五味子醇甲在0.97～29.13μg﹒mL^-1范围内呈良好的线性关系（r=1.000 0）,平均回收率为98.90%,其RSD值为1.9%（n=6）。结论 改进后的方法合理可行,重复性好,可用于养阴镇静丸的质量控制。     

HPLC法测定注射用益气复脉（冻干）中五味子醇甲、五味子醇乙、当归酰戈米辛Q和当归酰戈米辛H

目的 建立HPLC法同时测定注射用益气复脉（冻干）（YQFM）中五味子醇甲、五味子醇乙、当归酰戈米辛Q和当归酰戈米辛H 4种木脂素类成分的含量。方法 采用Phenomenex Luna 5u C₁₈（2） 100A柱（250 mm×4.6 mm,5 μm）,以乙腈-0.05%磷酸水梯度洗脱,体积流量1.0 mL/min,柱温30℃,检测波长220 nm。进行专属性、线性关系、加样回收率、重复性、稳定性、耐用性、方法适用性考察。结果 4种木脂素成分在各自浓度范围内线性关系良好（r>0.999）;加样回收率为93.09%、88.25%、90.69%、91.08%,RSD均小于2%;重复性、稳定性、耐用性结果均符合要求;选取21批YQFM样品进行含量测定,方法适用性良好。结论 所建立的方法准确可靠,可用于YQFM中五味子醇甲、五味子醇乙、当归酰戈米辛Q和当归酰戈米辛H 4种木脂素类成分的含量测定。     

UHPLC测定芎菊上清丸中9种成分含量及化学模式分析

目的 建立UHPLC波长切换法同时测定芎菊上清丸中9种成分的含量方法。方法 采用Agilent Ecilipse C₁₈（2.1 mm×100 mm,1.6 μm）色谱柱,流动相：甲醇-0.05%磷酸水溶液,梯度洗脱;流速为0.3 mL·min^-1;检测波长：327,237,320,345,278,254 nm;柱温30℃;进样量2 μL;并采用SPSS 22.0统计软件对含量测定结果进行主成分分析与聚类分析。结果 绿原酸、3,5-二咖啡酰奎宁酸、栀子苷、甘草苷、阿魏酸、盐酸小檗碱、黄芩苷、升麻素苷、5-O-甲基维斯阿米醇苷线性范围分别为4.30~68.80 μg·mL^-1（r=0.999 0）、6.66~106.56 μg·mL^-1（r=0.999 2）、7.67~122.72 μg·mL^-1（r=0.999 4）、4.88~78.08 μg·mL^-1（r=0.999 1）、2.37~37.92 μg·mL^-1（r=0.999 1）、6.50~103.92 μg·mL^-1（r=0.999 2）、8.85~141.60 μg·mL^-1（r=0.999 4）、0.88~14.08 μg·mL^-1（r=0.999 7）、0.74~11.92 μg·mL^-1（r=0.999 3）;平均加样回收率（n=9）均在99.42%~103.10%,RSD均<2.0%。主成分分析与聚类分析均可将不同生产厂家的芎菊上清丸很好地分类,且分类结果一致。结论 所建立的多成分方法快捷、准确、重复性好,可用于芎菊上清丸的质量控制。     

HPLC波长切换法同时测定心神安胶囊中9种成分的含量

目的 建立HPLC波长切换法同时测定心神安胶囊中9种成分的含量。方法 采用Agilent Eclipse XDB-C₁₈色谱柱,流动相乙腈（A）-0.1%甲酸溶液（B）,梯度洗脱;流速0.9 mL·min^-1;检测波长分别为320 nm[检测远志（口山）酮Ⅲ、3,6''-二芥子酰基蔗糖]、203 nm （检测人参皂苷Rb₁、绞股蓝皂苷XLIX、绞股蓝皂苷XVⅡ）和254 nm （检测毛蕊异黄酮葡萄糖苷、芒柄花苷、毛蕊异黄酮、芒柄花素）;柱温25℃。结果 远志（口山）酮Ⅲ、3,6''-二芥子酰基蔗糖、人参皂苷Rb₁、绞股蓝皂苷XLIX、绞股蓝皂苷XVⅡ、毛蕊异黄酮葡萄糖苷、芒柄花苷、毛蕊异黄酮、芒柄花素分别在2.070~41.40 μg·mL^-1（r=0.999 2）、3.860~77.20 μg·mL^-1（r=0.999 6）、11.29~225.8 μg·mL^-1（r=0.999 8）、5.070~101.4 μg·mL^-1（r=0.999 9）、19.86~397.2 μg·mL^-1（r=0.999 5）、1.280~25.60 μg·mL^-1（r=0.999 1）、0.960 0~19.20 μg·mL^-1（r=0.999 3）、0.670 0~13.40 μg·mL^-1（r=0.999 7）、2.580~51.60 μg·mL^-1（r=0.999 1）内线性关系良好,平均回收率分别为98.04%,99.26%,99.05%,97.42%,100.0%,98.27%,97.81%,96.84%和99.86%,RSD分别为1.28%,0.82%,1.43%,1.43%,0.86%,1.26%,1.38%,1.16%和0.69%。结论 本方法操作简便、准确、重复性好,能够对心神安胶囊中9种成分进行同时含量测定,为提高和完善心神安胶囊的质量标准提供了有效方法。     

一测多评法检测六味五灵片中6种成分的含量

摘 要 目的：建立一测多评(QAMS)法测定六味五灵片中连翘苷、五味子醇甲、五味子酯甲、五味子甲素、五味子乙素和五味子丙素等6种有效成分的含量,验证该方法在制剂中应用的准确性和可行性。方法: 采用HPCL法,在230nm检测波长下建立五味子甲素与五味子乙素、五味子丙素、五味子酯甲、五味子醇甲和连翘苷的相对校正因子(f),计算六味五灵片中各成分的含量,实现一测多评。同时采用外标法测定,并计算QAMS法含量计算结果(W_f)和外标法含量测定结果(W_s)的相对误差,验证一测多评法的准确性,并对其重现性进行考察。结果: 建立用于测定六味五灵片中6种成分含量的QAMS法,并对10批制剂中六味五灵片的指标成分进行测定,其计算值与测定值的差异较小(RSD＜5%)。结论:QAMS法用于测六味五灵片6种有效成分的含量,方法简单、有效、结果准确。QAMS法测六味五灵片的质量评价模式得到了验证,可用于六味五灵片的质量控制,并为后续的一测多评的研究提供参考价值。     

UPLC-MS/MS法测定比格犬血浆中五味子醇甲的血药浓度

目的 建立UPLC-MS/MS测定比格犬血浆中的五味子醇甲血药浓度分析方法。方法 采用ACQUITY UPLC^® BEH C₁₈色谱柱（50 mm×2.1 mm,1.7 μm）,流动相为0.1%乙酸水-甲醇梯度洗脱,体积流量为0.4 mL/min。柱温40℃,进样量5 μL。采用电喷雾（ESI）正离子模式进行多反应（MRM）监测,五味子醇甲和利伐沙班（内标）的定量离子对分别为m/z 433.20→384.30、437.19→145.13。结果 五味子醇甲在0.2～100 ng/mL线性关系良好（r=0.999 6）,最低定量限为0.2 ng/mL,批内、批间精密度分别为2.04%～7.62%、3.72%～8.29%;基质效应及提取回收率分别为95.7%～103%、81.2%～106%;稳定性结果均符合生物样品检测指导原则。结论 建立的UPLC-MS/MS方法快速、简单、灵敏度高,能满足五味子醇甲血药浓度测定及其药动学研究。     

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.

---

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.     

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.     

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.