黄芩炭饮片质量标准研究

目的建立黄芩炭的质量标准, 为其质量控制提供参考。方法取黄芩炭样品, 进行性状观察、薄层色谱(TLC)鉴别, 并按《中国药典(2020年版)》通则方法测定其中水分、总灰分、醇溶性浸出物, 利用高效液相色谱法检测其中的黄芩素含量, 并建立黄芩炭的特征图谱。结果黄芩炭为类圆形或不规则形段或片, 片面黑褐色, 内部黄褐色, 质松脆, 有焦糊气, 味苦。供试品TLC图中, 在对照品(黄芩素、汉黄芩素)以及对照药材相对应位置上, 显示相同颜色的荧光斑点。10批黄芩炭中, 水分、总灰分、醇溶性浸出物分别为2.60%～7.36%、5.03%～8.92%、23.08%～48.92%, 平均值分别为5.20%、6.39%、32.84%;黄芩素含量为1.61%～4.33%, 平均值为2.67%。结论本研究在黄芩炭已有质量标准的基础上增加了水分、总灰分、醇溶性浸出物、特征图谱等检测项, 拟定了黄芩炭中水分、总灰分、醇溶性浸出物的最低限量, 黄芩炭样品应检出3个特征峰, 分别与黄芩苷、黄芩素、汉黄芩素对照品参照物峰保留时间一致。所建质量标准可为黄芩炭饮片的质量控制提供参考。     

海参药材质量标准提升的研究

目的 制定山东省地方习用药材海参的质量标准。方法 参照《中国药典》（2020版）相关方法对海参药材进行性状和薄层色谱（TLC）鉴别研究,测定了水分、酸不溶性灰分及浸出物的含量;通过硫酸苯酚法以葡萄糖为对照品测定海参多糖的含量;采用高效液相色谱法（HPLC）对海参药材的特征图谱进行研究。结果 不同批次海参药材的性状特征较一致;TLC斑点清晰,重复性好;海参药材中水分的质量分数为8.5% ~ 9.5%,酸不溶性灰分的质量分数为0.1% ~ 0.2%,浸出物的质量分数范围为33.6% ~ 51.7%;以葡萄糖计海参多糖的质量分数范围为0.52% ~ 0.85%;供试品色谱图中呈现的5个特征峰与对照药材参照物色谱图中的5个特征峰的保留时间相对应。结论 本研究建立的定性及定量方法操作简便、准确、稳定。可用于海参药材的质量控制。     

市售天山堇菜药材质量评价研究

目的 补充提高维药天山堇菜药材质量标准。方法 采用生药鉴别方法对市售天山堇菜药材进行性状特征、显微特征及薄层色谱定性鉴别;采用Agilent TC-C₁₈色谱柱（4.6 mm×150 mm,5 μm）;流动相为乙腈-0.1%磷酸水溶液（15：85）;柱温35℃,检测波长349 nm,流速0.8 mL·min^-1,对天山堇菜药材中秦皮乙素含量进行测定。采用中国药典2015年版一部附录项下方法对天山堇菜中醇溶性浸出物、水分、总灰分和酸不溶性灰分进行测定。结果 对天山堇菜药材性状特征、显微特征进行了专属描述确定;10批市售天山堇菜药材进行了薄层定性鉴别;活性成分秦皮乙素在0.1~3.0 μg·mL^-1（r=0.999 3）内呈良好的线性关系,平均回收率为98.56%（RSD=1.90%）。确定了天山堇菜中秦皮乙素、醇溶性浸出物、水分、总灰分和酸不溶性灰分的检查限度。结论 补充提高建立的维药天山堇菜质量控制方法简便、准确、稳定,可以用于天山堇菜药材的质量控制。     

槟榔药材C18柱化学特征图谱的研究

摘 要 目的:建立槟榔对照药材的C₁₈柱化学特征图谱和评价指标。方法: 以Inertsil ODS-3 C₁₈(250 mm ×4.6 mm,5 μm）为色谱柱;以甲醇-0.15%三乙胺溶液（磷酸调pH至6.5）（13∶87）为流动相,检测波长为215 nm。结果:供试品特征图谱中呈现3个特征峰,与参照物峰相应的峰为S峰,计算各特征峰与S峰的相对保留时间。相对保留时间规定值：1.10（峰2）、1.63（峰3）。结论:14批样品的相似度均在0.9以上,且方法学考察的结果均符合指纹图谱技术要求。     

红旱莲药材的质量标准研究

目的 完善红旱莲药材的质量标准。方法 采用显微鉴别法、薄层色谱（TLC）法鉴别红旱莲;按《中华人民共和国药典》（2015年版）规定方法考察水分、总灰分、酸不溶性灰分和醇溶性浸出物;用HPLC法测定金丝桃苷的含量。结果 建立了红旱莲显微鉴别法和TLC法鉴别,HPLC法含量测定;确定了水分、灰分、醇溶性浸出物的限度。结论 本实验为红旱莲药材的质量标准提高提供了依据。     

西青果的质量标准提升和指纹图谱建立

目的 建立西青果Terminalia chebula Retz.诃黎勒酸和鞣花酸HPLC检测方法及指纹图谱鉴别方法，同时对15批次西青果药材进行质量标准研究。方法 收集3个道地产地15批次西青果药材，按《中国药典》中方法对西青果药材进行全检；新建诃黎勒酸和鞣花酸HPLC检测方法，流动相为甲醇-0.1%磷酸溶液，梯度洗脱，体积流量为1 mL·min^-1，检测波长为258 nm，柱温为35℃，进样量为5 μL，并进行方法学验证；同时建立西青果HPLC指纹图谱检测方法，进行多批次药材相似度分析，指认药材特征峰并进行聚类分析。结果 15批次药材检查结果均符合《中国药典》2020年版标准，薄层色谱法（TLC）结果显示，供试品在西青果对照药材色谱相应位置上显相同颜色的斑点；3产地15批西青果样品中水分、总灰分、酸不溶性灰分、水溶性浸出物（冷浸法）质量分数分别为6.74%～9.36%、2.41%～5.87%、0.05%～0.61%、51.03%～73.23%，平均值分别为7.66%、2.88%、0.22%、64.13%；新建立HPLC方法学考察均符合《中国药典》相关要求，15批次西青果药材中诃黎勒酸、鞣花酸质量分数为122.56～224.37、19.32～63.60 mg·g^-1。15批西青果指纹图谱相似度均大于0.90。结论 在西青果原有标准上增加灰分检查，新建诃黎勒酸和鞣花酸含量测定及指纹图谱方法，该方法专属性强，简便可靠，利用所建方法对不同产地批次的15批样品进行测定并综合评价，可为丰富该药材质量控制内容和药典修订提供依据。     

彝药水指甲药材的质量标准研究

目的:建立彝药水指甲药材的质量标准。方法:分别对水指甲药材进行性状鉴别和粉末显微鉴别,再以β-谷甾醇为对照品进行薄层色谱(TLC)鉴别;采用《中国药典》方法测定不同产地水指甲药材的水分、总灰分、酸不溶性灰分、醇溶性浸出物并制定其限度。结果:样品性状和显微鉴别特征明显,TLC特征斑点清晰,水分、总灰分、酸不溶性灰分、醇溶性浸出物的平均百分含量分别为9.5%、12.9%、2.6%、22.5%。结论:所建标准可用于水指甲药材的质量控制。     

大枣药材乙酸乙酯提取部分三萜酸类成分HPLC特征图谱研究

摘 要 目的：建立大枣药材乙酸乙酯提取部分三萜酸类成分HPLC特征图谱。方法: Vision HT C18 HL色谱柱（250 mm×4.6 mm,5 μm）;乙腈 0.1%乙酸铵(65 ∶〖KG-*4〗35)为流动相;流速：1.0 ml·min-1;检测波长：210 nm;柱温：30℃。运用中药色谱指纹图谱相似度评价系统进行分析。结果: 以大枣对照药材及白桦脂酸对照品为参照物,初步构建了由6个特征峰组成的大枣药材HPLC 特征图谱。结论: 所建立的特征图谱专属性强,重现性好,能够为大枣药材的质量评价提供科学依据。     

荔枝草的质量标准建立与探讨

目的 完善中药材荔枝草的质量标准。方法 采用显微鉴别、薄层鉴别、水分、总灰分、浸出物、含量测定等项目对荔枝草的质量进行考察。结果 荔枝草显微鉴别特征明显;薄层鉴别斑点清晰,易于识别;质量标准为：水分≤12.0%,总灰分≤10.0%,醇溶性浸出物≥20.0%;含量测定原儿茶酸在1.068~106.8 μg·mL^-1内呈良好的线性关系(r=0.999 7),其含量≥70 μg·g^-1。结论 荔枝草药材的显微鉴别、薄层鉴别、水分、总灰分、浸出物、含量测定研究可为该药材质量标准的修订、提高提供参考依据。     

市售全蝎炮制现状分析及盐制工艺优选

摘 要 目的：对124批次市售全蝎炮制现状进行分析;对全蝎盐制工艺进行优选。方法: 对市售全蝎性状、浸出物、水分、总灰分、酸不溶性灰分、氨基酸含量、重金属进行测定;以浸出物、氨基酸含量为考察指标,对全蝎盐制工艺进行优选。结果: 综合各项检测结果市售商品蝎质量差异较大;以2%氯化钠水溶液煮沸5 min炮制全蝎,其浸出物、氨基酸含量最高。结论:应修订现行标准中浸出物测定项,并可酌情增加水分、总灰分、酸不溶性灰分、氨基酸含量、重金属测定项以更全面的控制全蝎质量;全蝎盐制的最佳工艺为2%氯化钠水溶液煮沸5 min。     

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.     

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.     

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。     

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.     

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.     

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.     

Effect of bay K 8644, a calcium channel agonist,on dog cardiac muscarinic receptors

To investigate further whether the effects of the dihydropyridine (DHP) drugs on calcium channels are related to those of these drugs on muscarinic receptors, the binding characteristics of the DHP calcium channel agonist, Bay K 8644, on muscarinic receptors and calcium channels were compared to those of the DHP calcium channel antagonists, nicardipine and nimodipine in the dog cardiac sarcolemma. Bay K 8644, nicardipine and nimodipine inhibited the specific [³H]QNB binding with K _i values of 16.7μM, 3.5μM and 15.5μM respectively. Saturation data of [³H]QNB binding in the presence of these DHP drugs showed this inhibition to be competitive. Bay K 8644, like nicardipine and nimodipine, blocked the binding of [³H]nitrendipine to the high affinity DHP binding sites, but atropine did not, indicating that the muscarinic receptors and the DHP binding sites on calcium channels are distinct. The K _i value of Bay K 8644 for the DHP binding sites was 4 nM. Nicardipine and nimodipine (K _i :0.1–0.2 nM) were at least 20 times more potent than Bay K 8644 in inhibiting [³H]nitrendipine binding. Thus, the muscarinic receptors were about 4000 times less sensitive than these high affinity DHP binding sites to Bay K 8644. These results suggest that the DHP calcium agonist Bay K 8644 binds directly to the muscarinic receptors but its interaction with the muscarinic receptors is not related to its binding to the DHP binding sites on calcium channels.