甲磺酸伊马替尼的合成

以4-甲基-3-硝基苯胺为起始原料,经过缩合、还原、环合等反应制得抗肿瘤药物甲磺酸伊马替尼。并分别讨论了采用无水碳酸钾代替二异丙基乙胺、水合肼和普通催化剂代替铂炭催化剂以及采用异戊醇作为溶剂的优点。最终反应总收率超过50%,用高效液相色谱分析产品纯度在99.5%以上。     

2,2-二异丙基丙腈的合成

针对原有工艺条件的操作条件苛刻和反应原料贵的缺点,设计并实施了一种制备2,2-二异丙基丙腈的方法.首先,在吡啶的存在下,甲磺酰氯与异丙醇缩合制备异丙基甲磺酸酯.不经分离,直接与丙腈反应,在氨基钠的作用下发生缩合反应,合成得到2,2-二异丙基丙腈,总收率81.3％,含量98％.结果表明:能有效通过改变起始原料和工艺过程,使得原料易得,操作条件温和,更好地满足工业化生产要求,具有潜在的工业化价值.     

Design and Fabrication of Drug Delivery Devices with Complex Architectures Based on Three-dimensional Printing Technique

1Introduction Drugdeliverydevices(DDD)playanimportantrole incontrollingthedrugreleaseinadesignedmanner[1].AsanimportantkindofDDD,theimplantableDDDmay beusedtotreatsomedeceases,suchasdiabetes,antibi oticadministration,immunization,andtheboneinfectio ns[2].…     

乳酸左氧氟沙星的飞行时间质谱裂解规律研究

采用不同电子能量的 EI和不同反应气压力的 CI电离方式 ,研究了乳酸左氧氟沙星 ( LL)的半水合物飞行时间质谱 ( TOFMS)的裂解规律。结果表明 :乳酸左氧氟沙星难以产生喹诺酮特有的裂解产物 ;当电离能量为 2 5 e V时 ,所得 EI谱的碎片离子丰度明显大于 70 e V所得离子的丰度 ;当反应气由正常压力 1× 1 0 -2Pa降低到 1× 1 0 -3 Pa时 ,CI谱中碎片离子丰度由极小变大 ,其强度与 EI( 70 e V)所得离子丰度相当     

氨溴索联合左氧氟沙星对肺炎克雷伯菌生物膜抑制和清除能力的研究

目的：研究氨溴索联合左氧氟沙星对肺炎克雷伯菌生物被膜的抑制和清除作用,旨在为临床提供拮抗肺炎克雷伯菌生物膜形成和治疗的新策略。方法：收集不同耐药性肺炎克雷伯菌各15株,将其分为敏感组（野生菌组）、超广谱β-内酰胺酶（extended spectrum β-Lactamases, ESBLs）组、耐碳青霉烯类肺炎克雷伯菌（carbapenem resistant Klebsiella pneumoniae, CRKP）组,采用结晶紫染色法进行生物被膜半定量检测,再从各组中选取3株生物被膜产量相近的菌株,采用微量肉汤稀释法测定氨溴索和左氧氟沙星对肺炎克雷伯菌的最低抑菌浓度（MIC）;棋盘稀释法测定不同浓度氨溴索对左氧氟沙星MIC的影响以及通过计算部分抑菌浓度指数（FIC）判断联合效果和选择最佳协同浓度;采用结晶紫法联合激光扫描共聚焦荧光显微镜研究不同浓度药物对肺炎克雷伯菌生物被膜的形成抑制试验和清除试验。结果：3组细菌生物被膜均在第5天达到成熟,两两比较发现敏感组较ESBLs组和CRKP组更易形成且产量更多（F=3.725,P=0.032）;棋盘稀释法显示,随着氨溴索浓度的增加,3组细菌左氧氟沙星MIC值的几何均数均明显下降,呈显著的负相关,且联合药敏结果显示,两药组合均呈现协同作用;在生物被膜形成抑制试验中,随着氨溴索浓度的增加,其抑制率均达到了75%以上,但其生物被膜清除率却未达到70%。 结论：氨溴索联合左氧氟沙星对临床早期抑制肺炎克雷伯菌生物被膜形成具有指导意义,且其最佳协同浓度为0.49 mg/mL氨溴索+4 μg/mL左氧氟沙星。     

宁泌泰胶囊联合左氧氟沙星胶囊治疗慢性前列腺炎的临床疗效观察

目的观察宁泌泰胶囊联合左氧氟沙星胶囊治疗慢性前列腺炎的临床疗效。方法选择门诊慢性前列腺炎患者245例,采用随机对照分组试验,其中治疗组125例,对照组120例,治疗组内服宁泌泰胶囊联合左氧氟沙星胶囊,对照组单服左氧氟沙星胶囊。结果2周后,治疗组的总有效率为89.6%(112/125),对照组的总有效率为69.2%(83/120),2组比较差异有显著性(?2=15.74,P<0.05)。2组均未见明显不良反应。结论宁泌泰胶囊联合左氧氟沙星胶囊治疗慢性前列腺炎疗效显著。     

The effects of oxygenation aeration treatment on dissipation behaviors of tricaine mesylate in carp (Cyprinus carpio) muscle and water

Tricaine mesylate (MS-222) is one of the most used anesthetics in fish. It can be absorbed by the human body via food consumption, with related detriments to human health. In this study, a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was developed for the determination of MS-222 in carp muscle and water samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). For cleanup procedure, multiplug filtration cleanup (m-PFC) method with n-Hexane delipidation was adopted. The extraction solvent, cleanup methods and sorbents were optimized. All method validation parameters were in the acceptable range. The dissipation behavior study was followed by the method development. Firstly, the anesthesia dose and time were optimized in application study. Secondly, carps were revived for different period of time with (experimental group) and without (control group) the oxygenation aeration treatment to compare the dissipation rate of MS-222. After being anesthetized for 6 h at 50 mg/L and 12 h of elimination, the concentrations of MS-222 in crap muscle and water of experimental group was lower than those of control group. After 36 h of elimination under oxygenation aeration, over 90% of MS-222 was dissipated in carp muscle. The results showed that the half-life of MS-222 in carp muscle was 6.2 h. The findings suggested that the commonly-used oxygenation aeration treatment in aquaculture production had potential effects in accelerating the dissipation of MS-222 in carp and water. In this study, three days of withdrawal period was recommended in carps after MS-222 administration under oxygenation aeration.     

荷移分光光度法测定甲磺酸培氟沙星

根据甲磺酸培氟沙星能与茜素红在KH2PO4-Na2HPO4缓冲溶液中发生反应生成稳定的电荷转移配合物,建立了用分光光度法测定甲磺酸培氟沙星的简便快速的新方法.在所选定的最佳条件下,甲磺酸培氟沙星的浓度在10.0～200.0 mg/L范围内符合比尔定律,相关系数r=0.995,方法检测限为5.46 mg/L,对样品平行测定10次的相对标准偏差为3.1%,回收率在94.0%～103.1%之间.该法可用于片剂中甲磺酸培氟沙星含量的测定.     

Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients

Objective: This study aimed to design and characterize an inhalable dry powder of ciprofloxacin or levofloxacin combined with the mucolytics acetylcysteine and dornase alfa for the management of pulmonary infections in patients with cystic fibrosis.

Methods: Ball milling, homogenization in isopropyl alcohol and spray drying processes were used to prepare dry powders for inhalation. Physico-chemical characteristics of the dry powders were assessed via thermogravimetric analysis, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry and scanning electron microscopy. The particle size distribution, dissolution rate and permeability across Calu-3 cell monolayers were analyzed. The aerodynamic parameters of dry powders were determined using the Andersen cascade impactor (ACI).

Results: After the micronization process, the particle sizes of the raw materials significantly decreased. X-ray and DSC results indicated that although ciprofloxacin showed no changes in its crystal structure, the structure of levofloxacin became amorphous after the micronization process. FT-IR spectra exhibited the characteristic peaks for ciprofloxacin and levofloxacin in all formulations. The dissolution rates of micro-homogenized and spray-dried ciprofloxacin were higher than that of untreated ciprofloxacin. ACI results showed that all formulations had a mass median aerodynamic diameter less than 5?μm; however, levofloxacin microparticles showed higher respirability than ciprofloxacin powders did. The permeability of levofloxacin was higher than those of the ciprofloxacin formulations.

Conclusion: Together, our study showed that these methods could suitably characterize antibiotic and mucolytic-containing dry powder inhalers.     

丁香酚和三卡因甲磺酸盐在大口黑鲈中代谢残留的比较

为了确定大口黑鲈成鱼适合的麻醉方式和麻醉剂量,研究了不同浓度的丁香酚和MS-222对大口黑鲈的静水麻醉效果。在最适麻醉质量浓度下模拟运输24 h,记录24 h存活率并测定麻醉0.5、4、8、16和24 h后的血清生化指标、水质p H、氨氮以及麻醉剂的残留量。结果表明:随着丁香酚和MS-222浓度增加,入麻时间缩短,复苏时间延长;丁香酚和MS-222的最适质量浓度分别为18~20 mg/L、50~60 mg/L时,两麻醉组模拟运输和复苏24 h后的成活率为100%,显著高于无麻醉运输组的80%和90%(p<0.05);随着麻醉时间延长,丁香酚和MS-222组血清中的皮质醇(COR)分别从336.83pg/m L下降到291.41pg/m L,从286.11上升到367.05pg/m L(p<0.05),丁香酚组血清中的COR显著低于对照组;葡萄糖分别从14.36、7.48 mg/dL下降到7.36、3.11 mg/dL(p<0.05),而丁香酚组中乳酸脱氢酶(LDH)、碱性磷酸酶(AKP)、谷草转氨酶(GOT)、尿素氮(BUN)的浓度显著低于MS-222组(p<0.05);残留检测结果表明在麻醉0.5h时,鱼肉中丁香酚含量达到最大值5.14mg/kg,在清水中复苏1d时丁香酚残留量为0.45mg/kg;而MS-222组在8 h残留量达到最大值为36.24 mg/kg,复苏4 d时基本消除完全。结果显示,丁香酚剂量小,代谢快,在诱发氧化应激和组织损伤时有较少的副作用。