鼻渊净胶囊的HPLC指纹图谱研究

目的 建立鼻渊净胶囊的高效液相色谱（HPLC）指纹图谱。方法 采用Agilent SB-C₁₈（4.6 mm×250 mm,5 μm）色谱柱,乙腈-水为流动相、以1.0 ml/min流速行梯度洗脱,检测波长210 nm,柱温30 ℃,洗脱时间为80 min。采用中药色谱指纹图谱相似度评价系统（2004A版）对检测出色谱进行指纹图谱相似度评价。结果 建立了鼻渊净胶囊的HPLC指纹图谱,确定了20个共有峰,15个峰归属到各药材,其中5个峰确认了化学成分;10批样品的指纹图谱的整体相似度与对照图谱比较,均在90%以上。结论 所建立的鼻渊净胶囊指纹图谱有助于从整体上控制该制剂的质量。     

酸枣叶HPLC指纹图谱研究

目的 建立酸枣叶药材的HPLC指纹图谱,为其质量标准的研究提供依据。方法 采用Kinetex C₁₈色谱柱（100 mm×2.1 mm,2.6 μm）;流动相为乙腈-0.1%磷酸酸水溶液,梯度洗脱;体积流量为300 μL/min;柱温30℃,检测波长225 nm,进样量10 μL,对12批酸枣叶药材进行了指纹图谱研究,采用中药色谱指纹图谱相似度评价系统（2012版）软件进行分析。结果 12批酸枣叶的HPLC指纹图谱有13个共有峰,其中1个共有峰得到确认,相似度均＞0.85。结论 该方法准确可靠,重复性好,为更好地控制酸枣叶内在质量提供科学依据。     

黄芩药材指纹图谱研究

摘 要 目的: 建立院内制剂生产采购黄芩药材的HPLC指纹图谱分析方法,为制剂内在质量评价积累数据。方法: 采用HPLC方法,以SHIMADZU VP-ODS C₁₈色谱柱(150 mm×4.6 mm,5 μm);流动相甲醇-0.2%磷酸水(47∶53)等度洗脱;检测波长为280 nm;柱温为30℃;流量为1.0 ml·min^-1,进样量:5 μl。结果:建立黄芩药材指纹图谱,以5号色谱峰黄芩苷为参照峰,确定10个共有峰,测定了11批样品,样品指纹图谱相似度均大于0.8。结论:从整体上显示了购进的不同批次黄芩药材成分特征变化趋势,建立的HPLC指纹图谱方法为含黄芩的院内制剂质量控制提供有效手段。     

毛叶香茶菜HPLC指纹图谱的建立及其液-质联用分析

目的 建立毛叶香茶菜药材的HPLC指纹图谱,并通过UPLC-ESI-MS技术对毛叶香茶菜药材中的化学成分进行定性分析。方法 采用Kromasil 100-5 C₁₈色谱柱（250 mm×4.6 mm,5 μm）,甲醇-0.1%冰醋酸为流动相梯度洗脱,流速为1 mL·min^-1,检测波长为239 nm,柱温为30℃。结果 建立了毛叶香茶菜药材的指纹图谱,标定了12个共有色谱峰,通过对照品指认、文献比对以及高分辨质谱数据解析,初步鉴定指认了其中7个共有峰化学成分。结论 该方法准确可靠、重复性较好,科学、有效地对毛叶香茶菜进行了整体评价,为更好地控制毛叶香茶菜内在质量提供了科学依据。     

橘叶UPLC指纹图谱和化学模式识别研究

目的 建立橘叶UPLC指纹图谱,对不同产地药材进行质量评价,为科学评价各批次橘叶质量提供依据。方法 采用Acquty UPLC BEH C₁₈（100 mm×2.1 mm,1.7 μm）色谱柱,以0.2%甲酸水溶液-甲醇为流动相进行梯度洗脱,体积流量为0.3 mL/min,柱温为26℃,检测波长为330 nm。结合聚类分析和主成分分析对20批不同产地橘叶药材的整体质量进行评价。结果 建立20批橘叶的UPLC对照指纹图谱,标定27个共有峰,聚类分析分成4类,利用主成分分析进行验证且确定6个决定峰。结论 结合化学计量学和UPLC指纹图谱为建立全面有效的橘叶药材质量控制模式提供参考。     

ASE-HPLC测定仙茅中仙茅苷的含量及其指纹图谱研究

目的 获得仙茅药材的HPLC指纹图谱,同时研究快速萃取仙茅中仙茅苷及其含量测定的方法,为其质量控制提供依据。方法 采用正交试验优选ASE 350快速溶剂萃取系统的最佳提取方法,采用HPLC测定仙茅苷的量,色谱柱为Thermo Syncronis C₁₈（100 mm×3 mm,3 μm）,流动相为乙腈-0.1%磷酸水溶液,梯度洗脱,体积流量为0.5 mL·min^-1,检测波长为285 nm,柱温为40℃。指纹图谱共有模式采用国家药典委员会中药色谱指纹图谱相似度评价系统（2.0版）进行处理分析。结果 采用萃取温度100℃、静态萃取时间5 min、循环提取2次的快速提取方法最优。在指纹图谱研究中,标定了15个共有峰,建立了对照指纹图谱,20批药材与共有模式之间相似性良好,相似度均>0.9。结论 本方法快速、准确,可用于仙茅药材的综合质量评价。     

肾康注射液指纹图谱的研究

目的 建立肾康注射液的超高效液相色谱（UPLC）指纹图谱,并对肾康注射液指纹图谱共有峰进行鉴定。方法 采用超高效液相色谱条件法,色谱柱ACQUITY UPLC^® CSH-C₁₈（2.1mm×100mm,1.7μm）,甲醇（A）-0.1%甲酸溶液（B）二元梯度洗脱,流速0.4 ml/min,检测波长280 nm,进样量2 μl,柱温30℃,使用飞行时间质谱仪,负离子模式扫描。结果 建立了肾康注射液UPLC指纹图谱,采用UPLC/ESI-Q-TOF MS技术共鉴定了26个共有峰。采用《中药指纹图谱相似度评价系统（2012.130723版）》评价了20批肾康注射液,指纹图谱相似度均大于0.90。结论 本方法所建立的肾康注射液指纹图谱灵敏度高,稳定可靠,为肾康注射液的质量控制提供了科学依据。     

注射用五味子提取物指纹图谱研究

目的 采用高效液相色谱法建立注射用五味子提取物指纹图谱,并对2015—2016年制备的40批注射用五味子提取物进行指纹图谱相似度分析。方法 试验考察了不同流动相组成和浓度、不同检测波长、不同洗脱方法、不同品牌C₁₈色谱柱（250 mm×4.6 mm,5 μm）、不同流速、不同柱温等条件下供试品溶液的色谱行为,利用中药色谱指纹图谱相似度评价系统对试验所得色谱图进行相似度分析。结果 确定了高效液相色谱检测条件,建立了20批注射用五味子提取物的对照指纹图谱（相似度不低于0.991）,确定了12个共有峰,并对5个共有峰进行了指认,其余20批供试品与对照图谱的相似度均值为0.994。结论 本试验建立的注射用五味子提取物指纹图谱可以为其质量控制提供科学的依据,为完善注射用益气复脉（冻干）质量标准提供数据支持。     

蒙药材蓝盆花指纹图谱及一测多评含量测定方法研究

目的： 建立蒙药材蓝盆花的HPLC指纹图谱及一测多评法同时测定绿原酸、木犀草苷、异绿原酸A及异绿原酸C 4个成分的含量,评价药材质量。方法： 采用Kromasil 100-5-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,以乙腈-0.2%磷酸溶液为流动相,梯度洗脱,流速1.0 mL·min^-1,检测波长分别为326 nm（含量测定）和350 nm（指纹图谱）,柱温30℃。以17批样品建立指纹图谱共有模式。以异绿原酸A为内参物,建立绿原酸、木犀草苷、异绿原酸C与内参物的相对校正因子,计算含量,并与外标法计算结果进行比较。结果： 建立了蓝盆花药材的HPLC指纹图谱,标示了10个共有峰,并指认其中的7个色谱峰,分别为绿原酸、木犀草苷、异绿原酸A、大波斯菊苷、异绿原酸C、木犀草素、芹菜素。相对校正因子重现性良好,以异绿原酸A为内参物采用校正因子计算的含量值与实测值之间无显著差异。结论： 采用指纹图谱与多指标检测模式可为评价蒙药材蓝盆花的质量提供有效方法。     

基于指纹图谱和网络药理学的白术质量标志物预测分析

目的：基于指纹图谱和网络药理学分析白术中潜在质量标志物(Q-Marker)并测定其含量。方法：采用 Waters Sun Fire C₁₈ 色谱柱(250 mm×4.6 mm,5 μm),以水(A)-乙腈(B)为流动相,梯度洗脱,流速1 mL·min^-1,检测波长切换测定,柱温30 ℃,进样量 10 μL,建立白术药材指纹图谱, 对32批白术药材进行相似度评价,确认共有峰并进行指认,再通过网络药理学方法构建“活性成分-靶点-通路”网络图,预测 Q-Marker,并测定其含量。结果：建立了32批白术药材指纹图谱,确认了 28 个共有峰,通过白术对照品指认4个色谱峰,分别为白术内酯Ⅰ、白术内酯Ⅱ、白术内酯Ⅲ、苍术酮; 经网络药理学确认以上 4 种成分为活性成分,可作用于 16个核心靶点、20 条关键通路发挥抗癌、抗炎、改善胃肠道疾病作用,初步预测白术内酯Ⅰ、白术内酯Ⅱ、白术内酯Ⅲ、苍术酮为潜在Q-Marker, 白术药材中其总质量分数不低于1.79 mg·g^-1。结论：白术潜在Q-Marker预测分析为建立一整套质量控制评价体系提供参考,为阐明其药效物质基础的作用机制奠定基础。     

Synthesis and evaluation of 2,6-piperidinedione derivatives as potentially novel compounds with analgesic and other CNS activities

New 2,6-piperidinediones 2_a–g and 4_a–d were prepared by initial condensation of aromatic aldehydes or cycloalkanones with cyanoacetamide to give α-cyanocinnamides l_a–g or cycloalkylidenes 3_a,b which underwent Michae1 addition with ethyl cyanoacetate or diethylmalonate. Compounds 4_a–d were alkylated by various alkyl halides to produce the N-alkylated 2,6-piperidinedione derivatives 5_a–m. Some new selected compounds 2_a–c,f, 4_a–d & 5_e,h,j were pharmacologically evaluated for potential anticonvulsant, sedative and analgesic activities. These compounds exhibited significant anticonvulsant and analgesic effects after a single I.P. administration 100 mg/kg b.wt. . On the other hand all the investigated compounds induced hypnotic activity and prolonged the phenobarbital sodium- induced sleep as compared with the control group and the most potent compound was found to be 2_f.     

NEURAMIDE STIMULATES ADRENOCORTICOTROPIN BUT NOT PROLACTIN RELEASE FROM RAT PITUITARY

Neuramide (NMD), a substance found in crude preparations of porcine stomach extract, is a viral inhibitor that also has putative immunostimulatory effects. The effects of NMD on stress-hormone (ACTH and prolactin—PRL) release were assessed inin vivoandin vitrostudies. In the former, blood levels of corticosterone and PRL were measured in NMD-treated male rats.In vitroexperiments were performed to evaluate the effects of NMD and three of its fractions (obtained with high performance liquid chromatography) on ACTH and PRL release from perfused rat pituitary slices. NMD increased plasma corticosterone levelsin vivoand produced dose-dependent increases inin vitropituitary release of ACTH. No effects on PRL secretion were observedin vivoorin vitro. The stimulatory effects on ACTH release were caused by the NMD fraction with a molecular weight of >5000<10000Da.     

EFFECT OF POLICOSANOL SUCCESSIVE DOSE INCREASES ON PLATELET AGGREGATION IN HEALTHY VOLUNTEERS

Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and type II hypercholesterolemic patients. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. The effect of successively increasing doses of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted in 37 healthy volunteers. The volunteers were on a placebo-baseline period (two tablets per day) for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10mgday⁻¹) for 7 days. After this period dosage was doubled to 20mgday⁻¹for the next 7 days and then again doubled to 40mgday⁻¹, while the control group received placebo tablets all the time. Platelet aggregation as well as coagulation time was measured at baseline and after each dosing step. Results showed that antiplatelet effects of policosanol were successfully enhanced throughout the study, thus suggesting a dose-dependent relationship. No significant effect was reached during the first dosing period, but significant reductions of epinephrine and ADP-induced platelet aggregation were observed after the second one. Finally, a significant inhibition of platelet aggregation induced by all the agonists was observed at the last dosing step. Coagulation time remained unchanged during the trial.     

Investigation of the prevalence of tetQ, tetX and tetX1 genes in Bacteroides strains with elevated tigecycline minimum inhibitory concentrations

In this study, the antibiotic susceptibilities to tigecycline and tetracycline of 35 selected Bacteroides fragilis group strains were determined by Etest, and the presence of tetQ, tetX, tetX1 and ermF genes was investigated by polymerase chain reaction (PCR). tetQ was detected in all 12 B. fragilis group isolates (100%) exhibiting elevated tigecycline minimum inhibitory concentrations (MICs) (≥8 μg/mL) as well as the 8 strains (100%) with a tigecycline MIC of 4 μg/mL, whilst tetX and tetX1 were present in 15% and 75% of these strains, respectively. All of these strains were fully resistant to tetracycline (MIC ≥ 16 μg/mL). On the other hand, amongst the group of strains with tigecycline MICs < 4 μg/mL (15 isolates), tetQ, tetX and tetX1 were found less frequently (73.3%, 13.3% and 46.7%, respectively). All but two strains harbouring the tetQ gene in this group were non-susceptible to tetracycline, with a MIC > 4 μg/mL. These data suggest that in most cases tigecycline overcomes the tetracycline resistance mechanisms frequently observed in Bacteroides strains. However, the presence of tetX and tetX1 genes in some of the strains exhibiting elevated MICs for tigecycline draws attention to the possible development and spread of resistance to this antibiotic agent amongst Bacteroides strains. The common occurrence of ermF, tetX, tetX1 and tetQ genes together predicted the presence of the CTnDOT-like Bacteroides conjugative transposon in this collection of Bacteroides strains.     

INDIRECT PARASYMPATHOMIMETIC ACTIVITY OF THE CLASS III ANTIARRHYTHMIC SUBSTANCE / -SOTALOLIN VITRO: REVERSIBLE INHIBITION OF CHOLINESTERASE ISOENZYMES FROM BLOOD AND THE HUMAN CENTRAL NERVOUS SYSTEM

Inhibitory effects of the class III antiarrhythmic compound / -sotalol on acetylcholinesterase (AChE; EC 3.1.1.7) isoenzymes of both erythrocytes and the human caudate nucleus and on serum cholinesterase (ChE; EC 3.1.1.8) were studiedin vitrousing a spectrophotometric kinetic assay with acetylthiocholine (ASCh) as substrate. Sotalol concentrations in the assays varied from 0.32 to 3.2m . All isoenzymes studied were inhibited by / -sotalol in a reversible and concentration-dependent manner. Double reciprocal plots of the reaction velocity against varying ASCh concentrations revealed that / -sotalol reduced substrate affinity (apparent Michaelis constant, KM, increased) of serum ChE, but did not change the enzyme's maximal rate of ASCh hydrolysis (V_max). Thus, / -sotalol inhibition of serum ChE was of the competitive type (rate constant for reversible competitive inhibition: K_i=0.51m ). In contrast, / sotalol reduced the maximal reaction velocity of the AChE isoenzyme from the central nervous system (caudate nucleus), but had no influence on substrate affinity of the enzyme (K_Mwith ASCh unchanged) indicating purely non-competitive inhibition kinetics (rate constant of reversible non-competitive inhibition: K_i′=0.44m ). / -sotalol inhibition of erythrocyte AChE was of mixed competitive/non-competitive type (K_i=0.31m , K_i′=0.49m ). Non-competitive / -sotalol inhibition of caudate nucleus AChE and the non-competitive component of erythrocyte AChE inhibition cannot be overcome by increased concentrations of the cholinergic transmitter acetylcholine (ACh). Peak / -sotalol plasma levels as described in the literature for both humans (15μ ) and experimental animals (dogs: 18μ ; rats: 260μ ) as well as maximal myocardial concentrations of the substance (dogs: 46μ ; rats: 478μ ) are in the range of about 2% to 100% of the sotalol inhibition rate constants determined in the present paper for cholinesterase isoenzymesin vitro. Thus, / -sotalol inhibition of ACh hydrolysisin vivomay contribute to both the well known antiarrhythmic potential and proarrhythmic side effects of the compound.     

AMELIORIATION OF CHEMICALLY-INDUCED HEPATOCYTE INJURY BY CYCLOSPORINE A

Cyclosporine A, beside its current applications, possesses potential hepatoprotective effects. This study was directed to investigate the effect of Cyclosporine A pretreatment on hepatic injury due to carbon tetrachloride (CCl₄) and -galactosamine. Rats were injected by two successive doses of Cyclosporine A (5mgkg⁻¹day⁻¹). Six hours after the second dose, 1mlkg⁻¹of CCl₄was administered i.p. Effects associated with Cyclosporine A pretreatment were examined by using isolated hepatocytes and hepatocytes that were immobilized and continuously perfused. -Galactosamine (5m ) was added directly to the perfusion medium. After isolation, hepatocytes were examined histologically by light and electron microscopy, immobilized and perfused for further metabolic functional activity evaluation. Cyclosporine A pretreatmentin vivoproduced hepatoameliorative effects of various degrees which were statistically significant as manifested by: (1) an increased trypan blue exclusion after CCl₄; (2) an improved ureagenesis after CCl₄; (3) a reduction in the lipid droplets accumulation in the cytoplasm produced by CCl₄administration; (4) well preserved cytoplasmic organelles as mitochondria, endoplasmic reticulum ER, nuclear chromatin structures that were altered by CCl₄; and (5) an increased hepatocytes survival in the agarose gel matrix, reduction of LD leakage and improvement of ureagenesis after -galactosamine addition to the perfusion medium. The beneficial effect of Cyclosporine A pretreatment in modifying hepatotoxicity of chemical insults merits further studies.     

栝楼不同药用部位质量控制的研究进展

瓜蒌子、瓜蒌皮、瓜蒌、天花粉来源于栝楼的不同药用部位,4味药材均为常用的大宗药材,现行版《中国药典》对其制定的质量标准过于简单,无法科学合理地控制其质量。本文对瓜蒌子、瓜蒌皮、瓜蒌、天花粉安全性和有效组分的研究进行综述,明确了相关研究存在的问题并针对问题提出建议,为科学全面的药材及饮片标准的制定提供参考依据。     

喙果黑面神化学成分研究

目的研究大戟科植物喙果黑面神(Breynia rostrata Merr.)的化学成分。方法利用硅胶、凝胶等色谱技术分离纯化化学成分,根据化合物的理化性质和光谱数据进行结构鉴定。结果从喙果黑面神的正丁醇萃取部分分离得到4个化合物,分别鉴定为6-O-甲基丙酰基-α-D-吡喃葡糖(6-O-methylpropanoyl-α-D-glucopyranose,1);4″-苯酚基-6-O-甲基丙酰基-β-D-吡喃葡糖苷(4″-phenolic-6-O-methylpropanoyl-β-D-glucopyranoside,2);1-O-没食子酰基-β-D-吡喃葡糖苷(1-O-galloyl-β-D-glucopyranoside,3);熊果苷(arbutin,4)。结论化合物1和2为新化合物,3和4均为首次从该种植物分离得到。     

EFFECTS OF 2-GUANIDINE-4-METHYLQUINAZOLINE ON GASTRIC ACID SECRETION IN RATS

In this study 2-guanidine-4-methylquinazoline (2-GMQ) appeared to decrease basal and stimulated gastric acid secretion, while structurally related compounds as dimethyl- biguanide, cyanoguanidine and 2-cyanoamino-4-methylpyrymidine did not. Thus, there is an antisecretory effect when the biguanide group is associated with a lipophilic structure. The antisecretive effects exerted by 2-GMQ are associated with anti H₂-histamine activity.The anti H₂-histamine nature of the effects of 2-GMQ was confirmed by the capacity of this compound of depressing the chronotropic activity of the isolated guinea pig auricle increased by histamine, as well as relaxant activity in rat uterus contracted by histamine, since both preparations are rich in H₂-histamine receptors.