应用粉末X射线衍射法测定地氯雷他定中晶型Ⅰ和晶型Ⅱ的比例

目的：用粉末X射线衍射法测定地氯雷他定原料中晶型Ⅰ和晶型Ⅱ所占重量百分比。方法：将晶型Ⅰ和晶型Ⅱ对照品按照5种不同比例混合后测定,以二者特征峰面积比对重量比绘制标准曲线,采用内标法和标准加入法相结合的方法计算两种晶型所占重量百分比。结果：线性方程为y=2.3205x-1.5641,r=0.9986,3批样品中晶型Ⅰ和晶型Ⅱ的百分比分别为94.8%,5.2%;94.5%,5.5%;92.8%,7.2%。结论：粉末X衍射法可以用于地氯雷他定中晶型Ⅰ和晶型Ⅱ的定量分析。     

I型胶原蛋白对斑马鱼模型促组织再生及抗炎作用研究

目的 观察I型胶原蛋白对斑马鱼模型的促组织再生及抗炎作用。方法 通过检测斑马鱼尾鳍再生面积和col1a1b基因的相对表达量，表征I型胶原蛋白促组织再生作用；通过测量斑马鱼皮肤中性粒细胞数量变化表征I型胶原蛋白的抗炎作用。结果 与模型对照组相比，I型胶原蛋白溶液处理斑马鱼尾鳍面积明显增大，中性粒细胞数量明显减少。I型胶原蛋白溶液处理后的斑马鱼col1a1b基因的相对表达量明显高于正常对照组。结论I型胶原蛋白对斑马鱼模型具有促组织再生及抗炎作用。     

粉末X-射线衍射法测定阿托伐他汀钙片剂中晶型Ⅰ的含量

目的 应用粉末X-射线衍射技术对片剂中阿托伐他汀钙的晶型Ⅰ含量进行定量分析。方法 采用缩短扫描范围,降低扫描速度,提高步进扫描时间的精细扫描方法,建立了晶型Ⅰ含量测定的线性方程y=3179.3x-304.56（r=0.992 3）,并经方法学验证。结果 对2个规格6个批号片剂的晶型Ⅰ含量进行了测定,结果发现片剂中晶型Ⅰ含量有一定的变化。结论 本法操作简单,在辅料没有干扰的情况下可用于片剂中阿托伐他汀钙晶型Ⅰ含量的定量分析。     

厄贝沙坦多晶型X-射线粉末衍射定量分析

目的 建立厄贝沙坦晶型原料药的晶型含量分析方法，为药品晶型质量控制提供技术支撑。方法 采用X-射线粉末衍射法表征厄贝沙坦晶型A和晶型B。分别选取晶型A的特征衍射峰2θ=4.65°和晶型B的特征衍射峰2θ=7.99°的峰面积比值为定量参数，建立标准曲线检测晶型B的含量。结果 晶型B在晶型A和晶型B混合物中含量为2%~50%（质量分数）内线性关系良好（r=0.999 5），方法仪器精密度为4.7%，检测限浓度为1.12%（S/N=4.4）。结论 本研究建立的方法准确方便，可用于厄贝沙坦原料晶型A和晶型B混合物中晶型B的定量分析。     

车前草中大车前苷的含量测定及提取工艺优选

目的 建立车前草中大车前苷的含量测定方法,并优选其提取工艺。方法 采用HPLC法测定大车前苷的含量,并通过正交设计考察乙醇浓度、用量及提取时间对车前草中大车前苷提取工艺的影响。结果 大车前苷在12.51~125.10 μg/ml浓度范围内,线性关系良好（r=0.999 6）,平均加样回收率为98.57%,RSD为1.45%;最佳提取工艺为10倍量60%乙醇提取2次,每次1 h。结论 本研究建立的含量测定方法简便、准确、重复性好;优选的提取工艺稳定可行。     

3,5-O-二咖啡酰基奎宁酸的制备及其对HeLa细胞的抗增殖活性研究

目的 制备高纯度3，5-O-二咖啡酰基奎宁酸，并评价其对人宫颈癌HeLa细胞的抗增殖活性。方法 采用柱色谱提取法和中压液相色谱法从奇蒿花中分离、纯化得到高纯度的3，5-O-二咖啡酰基奎宁酸。采用MTT法评价该化合物对人宫颈癌HeLa细胞的体外抗增殖活性。结果 柱色谱提取的提取率和中压液相色谱法的回收率分别为99.0%，61.2%，总回收率为54.0%。随着3，5-O-二咖啡酰基奎宁酸浓度升高，HeLa细胞存活率下降，细胞形态损伤增加，受试药物的IC₅₀值为26.5µg·mL^-1。结论 本研究提供了一种简单、高效、节能的3，5-O-二咖啡酰基奎宁酸制备方法。3，5-O-二咖啡酰基奎宁酸对HeLa细胞具有一定的体外抗增殖活性。     

海洋环肽stylissamide Ⅰ的全合成研究

目的 采用固相合成/液相环化方法合成海洋环肽stylissamide Ⅰ。方法 以2-氯三苯甲基氯树脂（简称二氯树脂）为载体,选用6-氯苯并三氮唑-1,1,3,3-四甲基脲六氟磷酸酯（HCTU）和N,N-二异丙基乙胺（DIPEA）为缩合试剂依次连接9-笏甲氧羰基保护的氨基酸,在三氟乙醇（TFE）的作用下将直链肽从树脂上切割下来,然后使用（3H-1,2,3-三唑并吡啶-3-氧基）三-1-吡咯烷基六氟磷酸盐（PyAOP）,N-羟基-7-氮杂苯并三氮唑（HOAt）和N-甲基吗啡啉（NMM）在溶液中完成环合,最后在三氟乙酸（TFA）的处理下脱去侧链保护基,获得环肽粗品。经反相高效液相色谱对所合成的环肽粗品进行纯化,终产物纯度98.9%。通过高分辨质谱、600 MHz ¹H-NMR和¹³C-NMR鉴定,确定所合成环肽为目标环肽。结果 首次完成海洋环肽stylissamide Ⅰ的全合成,总收率为67%。结论 此法具有快捷、简便、高效的特点,较好地为stylissamide Ⅰ的固相全合成提供了参考。     

青钱柳多糖提取分离纯化及生物活性的研究进展

目的 对青钱柳多糖（Cyclocarya paliurus polysaccharide,CPP）的提取分离纯化及生物活性研究进展作系统分析,为CPP的深度研发提供参考。方法 查阅国内外近10年有关CPP的提取分离纯化及生物活性研究的文献,对其分析,概括和总结。结果 目前用于CPP提取的方法有超声波辅助提取法、微波辅助提取法、回流提取法、热水浸提法、超声波-酶法及超高压萃取法;含量测定方法有苯酚-硫酸法和蒽酮-硫酸法、紫外分光光度法、高效液相色谱法、DNS比色法;分离纯化方法有离子交换树脂法、凝胶过滤柱色谱法、亲和色谱法。结论 各提取、分离纯化方法均具优缺点,应根据研究的目的、条件对其合理选择;CPP的生物活性研究已取得一定成效,但仅局限于粗提物,而对于开发更多符合临床需求的药物制剂及相关产品有待进一步研究。     

水痘带状疱疹病毒野毒株和疫苗株区分方法研究

目的：建立水痘带状疱疹病毒野毒株和疫苗株的聚合酶链反应和限制性片段多态性（PCRRFLP）区分方法。方法：对疫苗株和水痘临床患者疱疹液进行开放阅读框62（ORF62）区基因序列测定,确定可用于野毒株和疫苗株区分的单核苷酸的多态性（SNP）位点。PCR扩增含SmaⅠ、BssHⅡ和NaeⅠ酶切位点的基因（DNA）片段后进行限制性内切酶酶切,利用酶切图谱区分野毒株和疫苗株。结果：用PCR-RFLP分析疫苗株和疱疹液,疫苗株酶切图谱为SmaⅠ⁺BssHⅡ⁺NaeⅠ⁺,疱疹液酶切图谱为SmaⅠ^-BssHⅡ^-NaeⅠ^-。结论：基于ORF62区的106262（SmaⅠ）、107136（BssHⅡ）、107252（NaeⅠ）的PCR-RFLP可有效区分野毒株和疫苗株。     

红细胞分布宽度对AECOPD合并II型呼吸衰竭患者的预测价值

目的 探讨红细胞分布宽度(RDW)对慢性阻塞性肺疾病急性加重(AECOPD)合并II型呼吸衰竭的预测价值。方法 回顾性分析2017年1～12月安徽医科大学第三附属医院收治的165例AECOPD患者的临床资料,依据动脉血气分析分为II型呼吸衰竭组(85例)与无II型呼吸衰竭组(80例)。观察分析两组患者的临床资料。结果 II型呼吸衰竭组患者RDW为(14.92±1.69)%,高于无II型呼吸衰竭组,差异有统计学意义(P<0.05)。多因素logistic回归分析显示,RDW是影响II型呼吸衰竭的危险因素(OR=2.323,95%CI:1.643～3.285,P<0.001)。受试者工作特征曲线分析显示,RDW的曲线下面积为0.761(95%CI:0.687～0.835),RDW预测II型呼吸衰竭的截断值为14.05%,灵敏性、特异性分别为67.10%和78.70%。结论 RDW可以作为AECOPD合并II型呼吸衰竭的预测指标。     

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.     

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.     

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,5μm)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...     

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.     

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.     

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.     

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。     

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.