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??OBJECTIVE To prepare inclusion complex of SBE₇-??-CD with trimethoprim(TMP) and optimize the preparation process, to evaluate the products by structural characterization and molecular simulation. METHODS The TMP/SBE₇-??-CD inclusion complex was prepared by the ultrasound-freeze-dry method and the preparation process was optimized by Box-Behnken Design-response surface method(BBD-RSM). Inclusion complex was characterized by FT-IR, DSC, XRPD and ¹H-NMR. Molecular docking method was used to simulate 3-dimensional conformations of the inclusion complex and the binding energy was calculated. The dissolution and stability were tested. RESULTS The optimum conditions of TMP/SBE₇-??-CD inclusion complex were: temperature(52 ??), time(45 min), and the ratio of SBE₇-??-CD and TMP(mol/mol, 1.7??1). All characterizations(FT-IR, DSC, XRPD and ¹H-NMR) indicated the formation of TMP/SBE₇-??-CD inclusion complex. The best 3-dimensional docking conformation was consistent with the characterizations, and the binding energy was -9.015 kcal??mol^-1. The TMP dissolution rate of the inclusion complex increased significantly, the hygroscopicity is strong. CONCLUSION The preparation process of TMP/SBE₇-??-CD inclusion complex optimized by BBD-RSM is reasonable and feasible. The characterizations of inclusion complex are reliable. The molecular simulation is corresponded to the characterized results and provided reliable theoretical basis for inclusion experiments.     

7-(吡啶-N-氧-2-巯基)-1-(2-氟乙基)-6,8-二氟-1,4-二氢-4-氧喹啉-3-羧酸的合成及抗菌活性

喹诺酮（亦称吡酮酸）类抗感染药物为广泛用于临床的高效、广谱、低毒性的抗感染化疗药物。目前国内外对喹诺酮类化合物的改造主要在７位,修饰取代基多为哌嗪、甲基哌嗪等仲胺类基团,而关于巯基类取代基的报道较少。作者根据喹诺酮类抗菌药和抗菌防腐剂２巯基吡啶Ｎ氧化物的抗菌作用原理设计、合成了７（吡啶Ｎ氧２巯基）１（２氟乙基）６,８二氟１,４二氢４氧喹啉３羧酸的７位巯基取代喹诺酮类化合物,并对其抗菌活性进行了研究,发现该化合物的抗菌活性优于国外近期上市的喹诺酮类抗菌药氟罗…     

气-人体-伤寒-鼻渊-百病-防治

据现代科学研究,宇宙起源于一次大爆炸,其原始状态为氢气,经核裂变而产生的大爆炸后乃渐次形成了各种元素,为各种生物体的形成创造了物质基础,而宇宙"黑洞"的超级向心力又为宇宙回到其初始状态不断的吸引压缩万物,百亿年后再次裂变爆炸,如此循环往复.     

4-氯-2-氧代-1,2-二氢喹啉-3-甲醛的合成工艺研究

目的：对4-氯-2-氧代-1,2-二氢喹啉-3-甲醛的合成工艺进行研究。方法以苯胺为原料通过酯的氨解、环合、胺亚甲基化、水解反应得到目标化合物。结果合成了目标化合物,并利用MS和1H-NMR确证了结构,此路线所得产品收率为62.1%。结论此路线操作简单,成本低廉,设计合理,收率高,适合该化合物的工业化生产。     

2，3-二氢-1-氨基-2-羟基-4-硝基茚的合成研究

最近几年，国外开发了不少以茚为母体的系列药物和兽药。如：以系列抗HIV药物L-689，502；L-685，927；L-735，524等、系列平滑肌迟缓药SARs及系列抗精神分裂药物。此外，作为农药应用，有日本开发的除草剂一茚草酮及美国杜邦公司于1992年开发，并于2001年登记上市的氨基甲酸酯类杀虫剂——茚虫威等。     

2,6-二甲基-4-(3-硝基苯基)-1,4-二氢-3,5-吡啶二羧酸-3-甲酯-5-正戊酯(MN9202)抗实验性血栓形成作用

 目的：探讨新的二氢吡啶钙通道阻滞剂MN9202对实验性血栓形成的影响及其作用机制。方法：采用iv胶原-肾上腺素或sc角叉菜胶，分别复制小鼠肺血栓和尾血栓模型。观察MN9202对实验性肺血栓小鼠死亡率，血栓黑尾形成率及微循环的影响。用凝血酶-ADP-肾上腺素复合诱导剂，复制大鼠脑血栓模型，观察MN9202对大鼠脑血栓损伤的预防作用。结果：MN9202 4mg·kg^-1ip，能明显降低胶原 肾上腺素引起的小鼠死亡率(30vs84P<0.01)；6mg·kg^-1ig，对凝血酶诱导的大鼠脑血栓损伤具有保护作用(0.069±0.068 vs 0.110±0.013,P<0.01);0.04,0.4mg·kg^-1能降低角叉菜胶诱导的血栓黑尾发生率(30,10 vs 90,P<0.05;P<0.01)，明显减轻微血管内皮的渗出，抑制血小板聚集和RBC聚集，改善微血管血流速度。结论：MN9202具有对抗血小板聚集诱导剂及角叉菜胶引起的血栓形成作用。其机制可能与其抑制RBC、血小板聚集，保护血管内皮，舒张痉挛血管有关。     

6-�л�-3-����-7H-����[3,2-b]-1,2,4-���-7-ͪ�໯����ĺϳɼ�������������ø���ƻ���

??OBJECTIVE To explore the synthesis and acetylcholinesterase inhibitory activity of 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives. METHODS Benzaldehyde and acetylglycine were used as raw materials and underwent Erlenmeyer-Pl??chl reaction, condensation reaction, hydrolysis reaction, condensation reaction to obtain 6-benzyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-ones derivatives. The derivatives reacted with substituted ??-phenacyl chlorides to generate 6-benzyl-3-(hydroxylaryl)-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones derivatives. Then, Williamson reaction was used to yield 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones as target compounds. RESULTS Nine 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones were prepared as target compounds. All target compounds exhibited inhibitory activities against human AChE in vitro, five of which had inhibitory rates above 50% at 10 ??mol??L^-1. CONCLUSION Based on the screening results of AChE inhibitory activity in vitro and docking studies, there are some interactions between 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives and the anionic binding site and PAS zones of AChE, and the target compounds have exhibited AChE inhibitory activities.     

D-α-������-��(2-�һ�-2-�ڶ�����)������������siRNA֬�ʸ�����Ĺ�������������

??OBJECTIVE To prepare small interfering RNA(siRNA) lipid complexes (TPOS-L/siRNA) modified by D-α-tocopheryl poly (2-ethyl-2-oxazoline) succinate (TPOS).METHODS The conventional siRNA lipid complexes (CLs/siRNA) and PEGylated CLs/siRNA (PEG-L/siRNA) were used as controls. CLs/siRNA was prepared by mixing blank CLs and siRNA directly of equal volume according to the electrostatic interaction of positive and negative charges. The encapsulation efficiency, morphology, stability, in vitro release and cell uptake of TPOS-L/siRNA were investigated.RESULTS The CLs/siRNA had obvious lipid bilayer structure, the encapsulation efficiency (EE) was (86.68±1.41)%, and the particle size of CLs/siRNA was less than 200 nm. The modification with TPOS or PEG-DSPE had no significant effect on the EE and particle size of CLs/siRNA, which could endow the lipid complexes with good stability. In addtion, TPOS-L/siRNA had good pH-sensitive property, and could respond to slightly acidic environment, which significantly enhanced the cell uptake.CONCLUSION TPOS can construct good siRNA carrier and increase the stability and pH sensitivity of the nanocarrier.     

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??OBJECTIVE To prepare the inclusion complex of Lignum dalbergia odorifera oil with hydroxyl-??-cyclodextrin(HP-??-CD), and to optimize the preparation process of it. METHODS The inclusion complex was prepared by the stirring-freeze-dry method. The preparation process was optimized by central composite design-response surface method (CCD-RSM),with the colligation score which was calculated by the yield of inclusion, the utilization rate of volatile oil and the content of trans-nerolidol as index. The inclusion complex was verified by phase-solubility method, DSC,UV and microscopical identification. RESULTS The optimum inclusion technology was: inclusion solvent 5% ethanol, stirring rate 500 r??min^-1, HP-??-CD to volatile oil 33??1, inclusion temperature 42 ??,inclusion time 2.5 h. The formation of inclusion complex can change the solubility, optical and thermodynamic properties of volatile oil. CONCLUSION The preparation process of inclusion complex of Lignum dalbergia odorifera oil with HP-??-CD optimized by CCD-RSM is reasonable and feasible, and provide a reliable experiment basis for its application.     

海桐中3个新的带3-甲氧基-5-酮-5,6-断-4,6-环-β端基的类胡萝卜素

曾报道了海桐花科植物海桐(Pittosporum tobira)籽中的C_(69)类胡萝卜素海桐黄质A1、A2的分离和结构。本次又从中分离出3个新的带有一个3-甲氧基-5-酮-5,6-断-4,6-环-β端基的类胡萝卜素(化合物1～3)。 海桐红色种子(20kg,日本京都产)经正己烷洗涤后,依次用甲醇、乙醚-正己烷(1∶1)提取,有机层用水洗涤后干燥并减压回收,残余物用5％氢氧化钾-甲醇在30℃     

1-[3-（3-苄基-4-乙氧基苄基）-4-氯苯基]-1,6-二脱氧-β-D-吡喃葡萄糖的合成工艺研究

目的：设计并合成1-[3-（3-苄基-4-乙氧基苄基）-4-氯苯基]-1,6-二脱氧-β-D-吡喃葡萄糖。方法以5-溴-2-氯-4＆#39;-乙氧基二苯甲烷为原料,通过Friedel-Crafts酰基化、还原、亲核加成、还原乙酰化、脱乙酰化反应的得到目标化合物。结果根据理化性质和波谱数据鉴定了目标化合物的结构,总收率为32%,质量分数为98.48%。结论1-[3-（3-苄基-4-乙氧基苄基）-4-氯苯基]-1,6-二脱氧-β-D-吡喃葡萄糖的合成为tianagliflozin中杂质的研究提供了方便。     

��Դ���񾭶���1-�׻�-6,7-���ǻ�-1,2,3,4-���������������ɭ��ģ���е��о���չ

??Endogenous neurotoxin 1-methyl-6,7-dihydroxy-1,2,3,4 -tetrahydroisoquinoline (salsolinol,Sals), an endogenous dopamine metabolite, were shown to be toxic to dopaminergic neurons in vitro as well as in vivo, and was known to be involved in the pathogenesis of Parkinson??s disease (PD). Sals is a more realistic model for selective toxicity to nigral dopaminergic neurons, and mimic the natural course of PD that develops slowly, allowing the brain to adapt to progressive damage. Sals lead to neurotoxicity in dopaminergic cells through induction of oxidative stress and apoptotic dopaminergic cell death,which made it as an important tool drugs to study the pathogenesis of PD.     

3-羰基-4-雄甾烯-17β-羧酸的合成

前列腺增生症 (ＢＰＨ)是老年男性最常见的疾病 ,也是导致男性排尿困难最常见的病因。近年来研究发现 ,维持前列腺生长发育的是二氢睾酮 (ＤＨＴ) ,而不是以往所认为的睾酮 (Ｔ) ,ＤＨＴ含量升高引起了ＢＰＨ[1] 。 5α 还原酶抑制剂能通过抑制Ｔ转化为ＤＨＴ而降低体内ＤＨＴ水平 ,达到治疗ＢＰＨ的目的。 5α 还原酶抑制剂是治疗良性前列腺增生症的一类新型特效药物 ,其中以Ｍｅｒｃｋ公司的非那雄胺 (ｆｉｎａｓｔｅｒｉｄｅ,Ｐｒｏｓｃａｒ)和ＳＫ＆Ｆ公司的依立雄胺 (ｅｐｒｉｓｔｅｒｉｄｅ)疗效为优。3 羰基 4 雄甾烯 17β 羧酸 (1)…     

4-（2＇,3＇;-二氯苯基）-1,4-二氢-2,6-二甲基-3-吡啶甲酸甲酯的合成

目的：设计并合成4-（2＇,3＇-二氯苯基）-1,4-二氢-2,6-二甲基-3-吡啶甲酸甲酯。方法以2,3-二氯苯甲醛为起始原料经缩合、环合、水解反应制备得到目标化合物。结果合成了目标化合物,并利用MS和1H-NMR确证了结构;HPLC归一化法测得质量分数为98.3%。结论4-（2＇,3＇-二氯苯基）-1,4-二氢-2,6-二甲基-3-吡啶甲酸甲酯的合成为丁酸氯维地平中杂质的研究提供了方便。     

高效液相色谱法测定2-(2,6-二氯苯基氨基)苯乙酸-4-(4-苯基-1,2,5-噁二唑-2-氧化物-3-)甲氧基苯甲酯原料药的研究

 目的采用反相高效液相色谱法建立2-(2,6-二氯苯基氨基)苯乙酸-4-(4-苯基-1,2,5-二唑-2-氧化物-3-)甲氧基苯甲酯(ZLR-8)原料药质量控制的方法。方法色谱柱为Lichrospher ODS柱(4.6 mm×250 mm),流动相为甲醇-乙腈-水(55∶20∶10),检测波长为226 nm,流速为1.0 mL·min^-1。结果中间体及各降解产物对样品测定不产生干扰,ZLR-8的浓度为11.18～223.6mg·L^-1时与峰面积呈良好线性关系(r=0.999 8,n=5),重复性良好(RSD%=0.47,n=6),检测限为54μg·L^-1。结论该方法可以用于ZLR-8原料药的含量测定和有关物质检查。     

2-(5-取代-1，3，4-噁二唑-2-亚甲硫)-5-吡啶-3-基-1，3，4-噻二唑的合成与抗癌活性

 目的研究含吡啶噻二唑噁二唑多杂环衍生物的合成方法及抗癌活性。方法吡啶噻二唑硫醇与噁二唑氯甲烷缩合得相应目标化合物、采用MTT法研究了目标化合物体外抑制L1210和B16癌细胞的活性。结果合成了5个新化合物,其结构经元素分析、IR、¹H-NMR、MS确证化合物4a,4c,4d,4e表现出比较明显的体外抗癌活性。结论含吡啶噻二唑噁二唑的衍生物有可能成为新型结构的抗癌候选药物。     

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??OBJECTIVE To investigate the pharmacokinetics and bioequivalence of hyaluronic acid-graft-poly(ethylene glycol)/??-cyclodextrin nanocapsules loaded with asparaginase(AHAPs) in SD rats. METHODS Rats were randomly divided into two groups. After intravenous injecting AHAPs and free AN, the activity of AN in two groups was assayed at different time points. The pharmacokinetic parameters were calculated by software DAS2.1.1 and the bioequivalence of free AN and AHAPs was judged. RESULTS AUC_{0-48 h} of AHAPs and free AN were (132.26??1.59) and (46.38??1.98) U??h??mL^-1. MRT_{0-48 h} of AHAPs and free AN were (3.64??0.04) and (1.76??5.99) h. The t_max of AHAPs and free AN were (0.75??0) and (0.08??0) h, respectively. The results showed that AUC_{0-48 h}, MRT_{0-48 h} and t_max of AHAPs increased to 2.85, 2.07 and 9.37 times, respectively, as compared with free AN. The 90% confidential intervals of AUC_0-48h, AUC_0-?? and ??_max of tested formulation were 77.0%-78.5%, 77.0%-78.5%, 94.4%-96.0%, respectively. The t_max checked by nonparametric method has significant difference (P<0.05) between AHAPs and free AN. CONCLUSION AHAPs can improve the bioavailability and extend the action time of AN in rats. AHAPs and free AN were not bioequivalent. And AHAPs had better pharmacokinetics properties in rats.     

中间体2-(2-羟乙基)-3-氨基-4-羧基吡唑的合成研究

 目的目的2-(2-羟乙基)-3-氨基-4-羧基吡唑是制备硫酸头孢噻利的重要中间体。方法经三步反应合成2-(2-羟乙基)-3-氨基-4-羧基吡唑:以氰乙酸乙酯为起始原料,与原甲酸三乙酯反应得2-氰基-3-乙氧基丙烯酸乙酯,与羟乙肼环合后再水解而得。结果在此条件下,收率可达60.8%。结论本实验方法与其他合成方法比较,具有收率高,操作容易,实用性强等特点,具有一定推广价值。     

铁皮石斛1-羟基-2-甲基-2-(E)-丁烯基-4-焦磷酸还原酶基因的克隆与表达分析

目的从铁皮石斛Dendrobium officinale中克隆1-羟基-2-甲基-2-(E)-丁烯基-4-焦磷酸还原酶[1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphatereductase,HDR]基因,并分析其在铁皮石斛不同组织中的表达差异以及不同信号分子诱导下的表达模式。方法采用RT-PCR和RACE等方法获得铁皮石斛HDR基因(Do HDR)全长,利用DNAMAN和MEGA6.0对其他物种的HDR基因编码的氨基酸序列进行同源性分析和进化关系分析,使用实时荧光定量分析HDR基因的表达模式。结果成功获得Do HDR基因,Gen Bank登录号为KC344827,全长1 658 bp,编码460个氨基酸,与其他科属植物的同源性达到80%以上。Do HDR基因在铁皮石斛叶片中表达量最高,从高到低依次是根、茎、原球茎;且受到脱落酸(abscisic acid,ABA)、水杨酸(salicylic acid,SA)信号分子的诱导。结论从铁皮石斛中获得Do HDR基因,为进一步阐明铁皮石斛萜类化合物合成途径中该基因的重要作用奠定了理论基础。