静脉药物配置中心常见不合理用药分析

 摘 要：目的 药师在静脉药物配置工作中的审核处方、医嘱，是有效减少不合理用药的重要环节。通过对静脉药物配置中心常见的不合理用药进行分析，以促进静脉药物的合理应用，从而提高静脉药物治疗的合理性、安全性、有效性。方法 将药师审核处方、医嘱工作中的不合理用药记录进行归类、统计。结果 不合理用药共有71条，比例为：0.2%。分析 不合理用药主要类型有5种，经药师干预不合理用药，及时与临床医师联系、沟通，并探讨合理用药，修正不合理用药处方、医嘱。一年后不合理用药比例下降70% 。     

芦丁-硒配合物的合成及抗肿瘤活性研究

 目的合成芦丁-硒配合物,并探讨其抗肿瘤活性。方法用芦丁跟氯化氧硒反应合成芦丁-硒配合物,采用四氮唑盐(MTT)法考察芦丁-硒配合物对CNE2(鼻咽癌)、HEP2(喉癌)、BEL-7404(肝癌)、KB(口腔上皮癌)及HELA(宫颈癌)的IC₅₀;同时考察了芦丁的抗肿瘤活性。结果目标化合物结构经紫外、红外、LC-MS及¹H-NMR确认。初步药理筛选结果显示:芦丁-硒配合物对CNE2、HEP2、BEL-7404、KB及HELA有显著的抑制作用,IC₅₀分别为26.78,0.42,8.37,1.89和0.35 mg·L^-1,芦丁则表现为促进CNE2、HEP2和BEL-7404细胞的体外增殖。结论合成出的芦丁-硒配合物具有较强的抗肿瘤活性,有关配合物的研究有待进一步深入。     

氨基酸改性熊果酸衍生物的合成及对胃癌细胞的抑制作用

 目的 合成具有伯氨基的氨基酸改性熊果酸衍生物并研究其对胃癌细胞的体外抑制活性及作用机制。方法 以乙二胺为连接臂,采用多种氨基酸对熊果酸C28位进行接合修饰,合成一系列氨基酸改性熊果酸衍生物。MTT法考察对胃癌细胞株BGC-823、AGS的体外抑制活性,同时采用Annexin V/PI双标记染色及细胞周期检测探讨其抗癌机制。结果 大部分衍生物对BGC-823、AGS的抑制活性强于熊果酸;Annexin V/PI双染色结果表明化合物3和4可诱导BGC-823发生凋亡;细胞周期检测表明衍生物3~6可诱导AGS发生凋亡,凋亡率达44.69%~92.64%。结论 带有伯氨基的氨基酸改性熊果酸衍生物具有良好的抗癌活性,其作用机制为诱导细胞凋亡;开发具有伯氨基的衍生物是提高熊果酸抗癌活性的可行途径之一。
     

ŵ�����ػ�ѧ�ɷּ��俹���������о�

??OBJECTIVE To study the chemical constituents of Noni enzyme (Morinda citrifolia L.) and their antitumor activities. METHODS Compounds were isolated by various chromatographic techniques, including silica gel, TLC, sephadex LH-20, and semi-preparative HPLC, and their structures were identified by their physicochemical properties and ¹H-NMR and ¹³C-NMR data. The in vitro antitumor activities of the isolated compounds were studied by MTT method. RESULTS Sixteen compounds were isolated from Noni enzyme. They were xylogranatinin(1), pelargonic acid(2), 1,5,15-tri-O-methylmorindol(3), sesquipinsapol B(4), (+)-syringaresinol(5), pinonesinol(6), 3-methylhexahydropyrrolopyrazine-1,4-dione(7), (2S)-3??-hydroxybutan-2-yl-2-hydroxypropanoate (8), 3-(sec-butyl)-6-methylpiperazine-2,5-dione(9), cyclo-(L-Pro-L-Leu)(10), gentisic acid(11), vomifoliol(12), scopoletin(13), 3-(2-hydroxy-4,5-dimethoxyphenyl) propanoic acid(14), medioresinol(15), hydroxychavicol(16). CONCLUSION Compounds 1-10, 12 and 14-16 are isolated from Noni enzyme for the first time. Compound 10 displays the stronger cytotoxicity against HepG2 and HeLa cells with an IC₅₀ value of 23.73, 16.55 ??g??mL^-1. Compound 5 had a certain inhibitory activity against HeLa cells with an IC₅₀ value of 47.12 ??g??mL^-1.     

4-氨基-2-三氟甲基喹唑啉衍生物的合成及其体外抗肿瘤活性研究

目的 基于喹唑啉为母核设计发现新型抗肿瘤活性化合物。方法 以邻氨基苯甲酰胺和三氟乙酸酐为起始原料采用缩合、环化、氯代和偶联反应等合成了一系列4-氨基-2-三氟甲基喹唑啉衍生物(5a~5u)。采用四甲基偶氮唑盐(MTT)法评价所得目标化合物对人肺癌细胞A549、人宫颈癌细胞Hela、人白血病细胞K562、人前列腺癌细胞PC-3、人前列腺癌细胞LNCaP这5种肿瘤细胞的体外增殖抑制活性。结果 化合物5c在5 μmol·L^-1时对PC-3肿瘤细胞的抑制率为49.3%,化合物6a对LNCaP和K562、以及6b对PC-3的抑制率超过了50.0%。结论 本实验设计合成的4-氨基-2-三氟甲基喹唑啉类化合物多数具有一定的抗肿瘤活性,特别是4-氨基的N-甲基化产物6a、6b的体外抗肿瘤活性较原型化合物(5n与5u)显著增强,为该类化合物的进一步研究提供参考。     

����������ͪ�ṹƬ�ε�c-Met���Ƽ�����ơ��ϳɼ��俹���������о�

??OBJECTIVE To design and synthesize 4-phenoxy-6,7-disubstituted quinolines possessing thiazolinone scaffolds and investigate their in vitro antitumor activities. METHODS Taking the c-Met kinase inhibitor cabozantinib as lead compound and based on the obtained SARs, combination principles and local modification, target compounds were prepared by nucleophilic substitution, nitration, reduction and condensation, etc. The c-Met inhibition and in vitro antitumor activities were evaluated by HTRF and MTT methods, respectively. The cytotoxicity against cancer cells was evaluated by real-time dynamic living cell imaging. RESULTS Seventeen novel compounds were obtained, and their structures were confirmed by ¹H-NMR, ¹³C-NMR and HRMS. In vitro bioassay indicated that all the compounds showed inhibitory activities against A549, HepG2 and MDA-MB-231 cell lines as well as c-Met kinase. Compound m2 exhibited potent cytotoxicity with IC₅₀ values of 2.45, 4.01, and 1.05 ??mol??L^-1, respectively. CONCLUSION The series of compounds show preferable antitumor activities, which are worthy of further study.     

甘草酸、甘草次酸衍生物的合成及生物活性研究进展

甘草酸、甘草次酸是甘草中最重要的活性成分,具有广泛的生物活性,尤其是其衍生物具有显著的抗炎、抗乙肝病毒、抗艾滋病毒等活性。近年来国内外专家合成了许多结构各异的甘草酸、甘草次酸衍生物,并研究了其相关的药理活性。文章综述了近年国内外对甘草酸、甘草次酸衍生物合成及活性研究所取得的新进展。     

������Ҷ��ѧ�ɷּ��俹���������о�

??OBJECTIVE To study the chemical constituents of the leaves of Magnolia grandiflora Linn and their antitumor activities. METHODS The constituents were isolated and purified by various chromatographic METHODS, including column chromatographies on silica gel, Sephadex LH-20, as well as recrystallization. Their structures were identified by analysis of physical and spectral data and confirmed by comparison of their spectral data with the reported values in the literature or those of authentic samples. The antiproliferative activities of the purified compounds were evaluated by MTT assay. RESULTS Twelve compounds were isolated and identified as parthenolide(1), ergosterol peroxide(2), N-formyl-annonain(Z)(3_Z), N-formyl-annonain(E)(3_E), vitamin E quinone(4), ??-sitosterol(5), 11,13-dehydrocompressanolide(6), scoparone(7), liriodenine(8), aurantiamide acetate(9), michelenollide(10), and 2,6,2??,6??-tetramethoxy-4,4??-bis(2,3-epoxy-1-hydroxypropyl)biphenyl(11). CONCLUSION Compounds 2, 3_Z, 3_E, and 4 are isolated from this plant for the first time. Compounds 9 and 11 are isolated from the plants in Magnoli Linn for the first time.     

8-��������߻�[3,2-d]����໯����ĺϳɼ��俹�������о�

??OBJECTIVE To synthesize the derivatives of 8-amino benzofuran[3,2-d]pyrimidine and study their anticancer activities.METHODS The target compounds were synthesized through a series of reactions, and their anticancer activities in vitro were evaluated against COLO205, MCF-7 and K562 cell lines by MTT as assay. RESULTS Nine title compounds were synthesized and confirmed by EI-MS,¹H-NMR and ¹³C-NMR.Compounds 2, 3d and 5c had good inhibition effect against COLO205, MCF-7 and K562 cells.The inhibition rates of compound 5c against COLO205, MCF-7 and K562 cells were 99.58%,78.75% and 98.68% respectively at 10^-4 mol??L^-1. CONCLUSION The anticancer activity of benzofuran[3,2-d] pyrimidine derivatives is worthy of further study.     

�����������ùAspergillus fumigatus YK-7����������л���Ｐ�俹���������о�

??OBJECTIVE To study the secondary metabolites of marine-derived fungus Aspergillus fumigatus YK-7. METHODS The compounds were isolated by several column chromatographic techniques, including silica gel, ODS, Sephadex LH-20 column chromatography, and HPLC, and their structures were identified on the basis of physicochemical properties and spectroscopic analysis. Trypan blue and MTT methods were applied for determining the effects of the compounds on proliferation of cancer cells in vitro. RESULTS Ten compounds were obtained, and their structures were identified as pseurotin A (1), pseurotin A₁(2), 14-norpseurotin A (3), FD-838 (4), demethoxyfumitremorgin C (5), 9??-hydroxyverruculogen TR-2 (6), 6-methoxyspirotryprostatin B (7), spiro[5H,10H-dipyrrolo[1,2-a:1??,2??-d]pyrazine-2-(3H),2??-[2H]indole]-3??,5,10(1??H)-trione (8), terezine D (9), and 14-hydroxyterezine D (10). CONCLUSION Compounds 3, 6, 7, 9, and 10 are isolated from marine-derived fungus Aspergillus fumigatus for the first time. Compounds 1-4 exhibite moderate antiproliferative activity against selected cancer cell lines in vitro.     

3-苯基-6-酰基吡咯吡嗪酮的合成及抗炎镇痛活性研究

 目的 研究吡咯并吡嗪酮类化合物的抗炎镇痛作用构效关系,寻找具有抗炎镇痛活性的新型吡嗪酮类化合物。方法 以2-甲基-3-苯基吡咯并吡嗪-1(2H)-酮化合物为母体,合成系列化合物。用二甲苯致小鼠耳肿胀法和醋酸致小鼠扭体法对所合成的目标化合物分别进行了抗炎和镇痛活性实验。结果 合成了11个目标化合物,经¹H-NMR和MS确证其结构。小鼠实验表明,一些所合成的化合物具有一定的抗炎或镇痛作用。结论 化合物14抗炎镇痛活性较好,值得进一步研究。     

羟基喜树碱微粉的制备及抗肿瘤活性

 目的 制备羟基喜树碱微粉（nHCPT）并考察其毒性和抗肿瘤活性。方法 本实验采用超临界流体抗溶剂法制备nHCPT,扫描电子显微镜（SEM）观察形态、原子力显微镜（AFM）检测其粒径。红外光谱（FTIR）和高效液相色谱确认nHCPT化学性质。气相色谱法测定nHCPT中残留DMSO含量。以HCPT和拓朴替原（TPT）为阳性对照,四甲基偶氮唑蓝（MTT）法检测nHCPT对PC-3、MCF-7和HCT-8细胞的生长抑制作用。显微操作系统观察HCT-8细胞对于nHCPT吸收。采用S180实体瘤模型,考察了nHCPT的抗肿瘤活性和对器官的毒性。结果 超临界处理后的nHCPT以无定型形态存在,粒径为（150±40）nm,形态为不规则球状结构,化学性质没有改变。nHCPT中残留DMSO含量符合ICH要求。样品在4 ℃、避光干燥条件下储存一个月后性质稳定。nHCPT对3种细胞株的抑制率略优于HCPT和TPT, nHCPT的细胞膜渗透能力较HCPT明显增强。nHCPT的体内抑瘤活性较HCPT明显提高,与TPT抑瘤活性相近,且对器官毒副作用明显低于TPT和HCPT。结论 nHCPT具有独特的优越性,可以作为进一步新制剂开发的原料药。     

刮筋板的化学成分和抗肿瘤活性研究

 目的 研究刮筋板 Excoecaria acerifclia F. Didr. 的化学成分和抗肿瘤活性。 方法 采用硅胶柱色谱, Sephedex LH - 20 分离化学成分 ; 根据波谱数据和理化性质确定化学结构;四甲基偶氮唑蓝（ MTT ） 法测定化合物对人肝癌细胞系 ( human hepatocarcinoma cell line ) HepG2 的 体外抑制作用,用半数抑制浓度 (IC₅₀) 评价其抗肿瘤活性。 结果 分离鉴定 6 个化合物,分别为：秦皮苷（ 1 ）、异落叶松脂醇 9-<>O -β-D- 葡萄糖苷（ 2 ）、 (-)-5 ′ -methoxyisolariciresinol 3a- O-β-<>D-glucopyranoside （ 3 ）、没食子酸（ 4 ）、 isostrictiniin （ 5 ）、 3-<>O- 阿魏酰基奎尼酸甲酯（ 6 ）;化合物 1 , 2 , 4 , 6 对体外培养肿瘤细胞的 IC₅₀ 分别为 14.71 , 26.52 , 34.91 , 65.42 μmol·L^-1 ; 在测定浓度范围内剂量依赖关系良好。 结论 所有化合物均为首次从该植物中得到;首次研究发现化合物 1 对 HepG 2 具有一定的抗肿瘤活性。     

水溶性壳聚糖-泼尼松龙结合物的合成与表征

 目的合成一系列不同相对分子质量(M_r)的水溶性壳聚糖-泼尼松龙结合物。方法通过控制壳聚糖的乙酰度得到水溶性壳聚糖(WCh i),并用凝胶渗透色谱测定其M_r大小。模型药物通过丁二酸间隔臂与WChi相连,其结构经红外光谱分析、差示扫描量热法分析、高效液相色谱分析和紫外光谱证明,结合的泼尼松龙量用高效液相色谱测定。结果合成的WChi的M_r分别为31×10³,19×10³,11×10³,7.2×10³,3.8×10³,相应的结合物中泼尼松龙含量分别为(8.36±0.04)%,(7.17±0.08)%,(7.21±0.03)%,(6.29±0.03)%,(6.66±0.05)%。结论成功制备了水溶性壳聚糖-泼尼松龙结合物。     

新型土震素B类似物的合成及其生物活性的研究

 目的研究新型土震素B类似物的合成及其生物活性。方法以乙酰乙酸乙酯为起始物,设计合成了含2H-吡喃-2-酮结构的化合物10a～10l;采用MTT法测试细胞毒活性,用ELISA法测试胆碱酯酶抑制活性。结果合成的土震素B类似物及其各中间体通过1H-NMR,ESI-MS和IR确定其结构。生物活性测试中化合物10f对AchE的IC₅₀为6.98×10^-5mol·L^-1,所有目标化合物在4.0 g·L^-1对丁酰胆碱酯酶均无抑制作用。结论初步探明了化合物10f对乙酰胆碱酯酶有一定的抑制活性,并且发现该类化合物有较好的选择抑制活性。     

��Ҷ�����ȼ��鲿λ��ѧ�ɷּ��俹���������о�

??OBJECTIVE To investigate the chemical constituents in chloroform extraction of Tetrastigmatis hemsleyani diels et. Gilg and their antitumor activities. METHODS Various chromatography techniques such as column chromatography on silica gel, Sephadex LH-20 and preparative TLC were used to isolate and purify the compounds. Their structures were identified by¹H-NMR,¹³C-NMR and MS. Their antitumor activities was tested by MTT method. Moreover, the other compounds of chloroform extraction were detected by GC-MS. RESULTS Six compounds were isolated by classic chromatography and identified as ??-sitosterol(1), 4-hydroxy-3-methoxybenzaldehyde(2), oleanolic acid (3), 5-hydroxymethyl furfural(4), azelaic acid(5), vanillic acid(6). Twenty-two compounds were identified by GC-MS. CONCLUSION Compounds 2-6 are isolated from this plant for the first time. Compounds 1 and 3 shows strong cytotoxic activities against Hela229 with IC₅₀ values of 40.78, 25.69 ??g??mL^-1, respectively. Compound 3 also showed strong cytotoxic activities against with IC₅₀ values of 69.87 ??g??mL^-1. The result proved that antitumor activity of chloroform extraction of Tetrastigmatis hemsleyani diels et. Gilg is due to the contribution of multi-components.
     

水杨酸糖酯制备及活性研究

目的：制备水杨酸糖酯,考察其刺激性和生物活性。方法：用羧酸有机碱法制备水杨酸糖酯;用1H-NMR和IR确认结构;用小鼠断尾法和小鼠耳肿胀法评价抗凝血活性和抗炎活性,组织切片法观察刺激性。结果：合成了4个β-构型的水杨酸糖酯,其中有3个的抗炎作用与阿司匹林相当,1个的抗凝血活性高于阿司匹林;合成物的刺激性均小于原药。结论：水杨酸糖酯类修饰可以降低刺激性。     

青蒿素半乳糖苷的抗肿瘤活性及其机制研究

目的:探讨青蒿素半乳糖苷体外抗癌活性及相关机制。方法:采用体外培养的Hela细胞株为研究对象,流式细胞仪检测青蒿素半乳糖苷作用后Hela细胞凋亡率,Caspase-3活性检测试剂盒检测Caspase-3活性,免疫印迹法检测细胞凋亡关键蛋白p53、BAX、Caspase-3、BCL-2的表达变化。结果:青蒿素半乳糖苷可诱导Hela肿瘤细胞凋亡,且呈剂量-效应关系;青蒿素半乳糖苷还可引发Hela肿瘤细胞Caspase-3活性水平升高,促凋亡蛋白Caspase-3、BAX高表达,抗凋亡蛋白BCL-2表达降低,且均呈现时间-效应关系。结论:青蒿素半乳糖苷具有明确的抑制肿瘤细胞的作用,其机制之一可能是通过不依赖于p53途径的BCL-2家族介导的细胞色素C通路引发肿瘤细胞的凋亡。     

����ؿ����������о���չ

??Cordycepin is a main active constituent of the famous traditional Chinese medicines Cordyceps sinensis and Cordyceps militaris. The antitumor activities and molecular mechanism of cordycepin on leukemia cells, lung cancer cells, hepatoma cells, prostatic carcinoma cells, cervical-cancer cells, colon cancer cells, leydig tumor cells, glioma cells and thyroid carcinoma cells were summarized.     

新型厚朴酚-二甲双胍缀合物对HepG2移植瘤小鼠抗肿瘤作用及机制研究

目的探讨新型厚朴酚-二甲双胍缀合物(MMC)对人肝癌细胞(HepG2)移植瘤小鼠的抗肿瘤作用及相关机制。方法将HepG2人肝癌细胞接种于雌性Balb/c小鼠构建肝癌移植瘤小鼠模型。将40只荷瘤小鼠随机分为对照组、顺铂组(2 mg·kg^-1)及MMC低、高剂量组(22、44 mg·kg^-1),共4组,每组10只;采用腹腔注射给药,连续给药21 d。记录小鼠体质量、测量并计算肿瘤体积;采用HE染色观察肿瘤组织病理形态;Tunel法检测小鼠肿瘤细胞凋亡情况;Western Blot法检测小鼠HepG2移植瘤组织中P-SAPK/JNK、p53、Bax、Bcl-2、细胞色素C(Cyt-C)、Pro-caspase 3和Cleaved-caspase 3等凋亡相关蛋白的表达。结果与对照组比较,各给药组荷瘤小鼠的体质量及移植瘤质量均明显降低(P<0.01),而MMC低、高剂量组去瘤小鼠的体质量明显增加(P<0.01),顺铂组去瘤小鼠的体质量明显降低(P<0.01);各给药组小鼠肿瘤组织的细胞排列相对紊乱,部分肿瘤细胞细胞核深染、固缩,表现出凋亡现象,肿瘤组织细胞凋亡率均明显升高(P<0.01);各给药组的Bax、Cleaved-caspase 3蛋白表达水平明显上调,Bcl-2蛋白表达水平明显下调(P<0.05,P<0.01);MMC低、高剂量组的p53蛋白表达水平明显上调(P<0.01);MMC高剂量组的P-SAPK/JNK蛋白表达水平明显上调,Pro-caspase 3蛋白表达明显下调(P<0.05);MMC高剂量组及顺铂组的小鼠移植瘤组织中线粒体内Cyt-C蛋白表达水平明显下调,细胞质内Cyt-C蛋白表达水平明显上调,差异均有统计学意义(P<0.01)。结论MMC能够抑制小鼠人肝癌细胞HepG2移植瘤生长,促进肿瘤细胞凋亡,可能与调节P-SAPK/JNK/p53信号转导通路诱发线粒体凋亡有关。