对甲苯磺酸催化合成肉桂酸异戊酯

目的:以对甲苯磺酸为催化剂对肉桂酸与异戊醇的液相酯化反应进行研究。方法:考察了醇酸比、反应时间、带水剂用量等因素对合成肉桂酸异戊酯的影响,得到合成该酯的较适宜条件。结果:最佳反应条件为n(醇):n(酸)=5:1,催化剂用量为肉桂酸用量的20%,反应时间2h,反应温度110～118℃,酯收率可达76.6%。结论:对甲苯磺酸是合成肉桂酸异戊酯的良好催化剂,具有实际应用价值,该实验合成工艺简单,酯收率较高。     

金属氯化物催化合成甲,乙,丙酸异戊酯

金属氯化物催化合成甲、乙、丙酸异戊酯ＳＹＮＴＨＥＳＩＳＯＦＩＳＯＡＭＹＬＦＯＲＭＡＴＥ，ＡＣＥＴＡＴＥ，ＰＲＯＰＩＯＮＡＴＥＢＹＣＡＴＡＬＹＳＩＳＯＦＭＥＴＡＬＣＨＬＯＲＩＤＥＳ杨仕豪李莉萍罗辉（广东医学院化学教研室，湛江５２４０２３）ＹＡＮＧＳｈｉ...     

异穿心莲内酯3,19-双酯类衍生物的合成与表征

目的 设计并合成异穿心莲内酯衍生物.方法 以DCC为缩合剂,DMAP为催化剂,合成异穿心莲内酯3,19-双酯衍生物.结果 合成并表征了9个异穿心莲内酯3,19-双酯衍生物及2个异穿心莲内酯19-单酯衍牛物.异穿心莲内酯与羧酸及缩合剂DCC的摩尔比为1.0;2.5;2.5,于室温下反应4～6 h.结论 所合成化合物结构均经1HNMR、MS确证.     

噻托溴铵的合成新工艺

本研究报道了一条合成噻托溴铵(1)的新方法.以双(2-噻吩)酮(2)为起始原料,经电羧化反应得到2-羟基-2,2-二(2-噻吩基)乙酸(3),3与东莨菪醇反应后,用饱和溴甲烷乙腈溶液甲基化,得到1.该工艺总收率74％(以2计),终产物纯度99.95％,改进后的工艺条件温和,避免了异构杂质的产生,降低了生产成本.     

超声波法合成3-肉桂酰异阿魏酸苯酯衍生物

异香(艹卓)醛和肉桂酸经酯化、与丙二酸在微波辐射下经Knoevenagel反应制得3-肉桂酰异阿魏酸后,再在超声波辐射下与取代酚酯化得到3-肉桂酰异阿魏酸苯酯,酯化收率为61%～84%.     

Hiyama反应催化合成沙坦联苯

目的:建立沙坦联苯的新合成方法,并优选合成工艺,以简化合成路线、减少环境污染。方法:以三甲氧基(对甲苯基)硅烷和邻溴苯腈为原料、异丙醇/水为溶剂(1∶1),经Pd Cl2/N-甲基亚氨二乙酸原位催化体系在80℃下反应24 h催化Hiyama偶联反应合成最终化合物,并对最终化合物进行核磁共振(1H-NMR、13C-NMR)表征。以收率为指标,对合成过程中氟离子量、三甲氧基(对甲苯基)硅烷和邻溴苯腈的投料比、反应温度、反应时间进行筛选。结果:表征结果显示最终化合物即为目标化合物,收率为63%,色谱纯度>99%。合成过程中氟离子量为1.5倍邻溴苯腈物质的量、三甲氧基(对甲苯基)硅烷和邻溴苯腈的投料比为1∶1.2、反应温度为80℃、反应时间为24 h时收率最高。结论:所建立的工艺路线具有原料易得、环保、收率高的特点,反应可在水和有机两相体系中进行,适用于沙坦联苯原料的放大制备和生产。     

取代苄基/萘甲基异喹啉类及有关季铵衍生物的合成与生物活性

以具心血管活性的异喹啉类生物碱为先导物,结合某些钾通道阻滞剂的结构特征,设计合成了28个3,4-二氢(I_1～4)和1,2,3,4-四氢苄基/萘甲基异喹啉化合物(II_1～18)及有关季铵衍生物(I_5,6和II_19～22)。药理试验表明:除化合物I₄有一定升压作用外,大多化合物有不同程度的降压和减慢心率活性,其中化合物II1的降压活性最强。分析定量构效关系发现:化合物母核氮原子电荷愈大(即其绝对值愈小),降压作用愈强;反之,减慢心率作用愈强。异喹啉母核氮原子电荷可能为影响作用于血管或心脏组织的重要因素之一。     

L-脯氨酸催化的(+)-laburnine和(-)-isoretronecanol的不对称合成

目的探索高效、简洁的(+)-laburnine和(-)-isoretronecanol不对称合成新方法。方法以已知化合物为起始原料,用L-脯氨酸催化的aldol自缩合反应,构建所需的手性中心,经Na BH4还原、保护、对甲苯磺酰化、亲核取代、水解、甲磺酰化、还原关环、脱保护共八步反应得到(+)-laburnine和(-)-isoretronecanol。结果经过八步合成了(+)-laburnine和(-)-isoretronecanol。结论总收率分别为27%和8%。     

4,5-二溴-3,6-二异辛基邻苯二甲腈的合成

目的：为了筛选4，5-二溴-3，6-二异辛基邻苯二甲腈最佳合成工艺。方法：以3，6-二羟基邻苯二甲腈和溴代异辛烷为原料在不同条件下经溴化、烷基化反应合成标题化合物，考察不同因素(温度、溶剂种类和用量等)对产物收率的影响。结果：溶剂的种类和用量、反应温度及脱氧剂的种类对产物收率的影响较大。结论；最佳合成工艺条件为：溶剂CH3COOH／CH3COOK，温度100℃，脱氧剂NaH。     

硫酸铵梯度法制备苹果酸舒尼替尼脂质体

目的:采用跨膜硫酸铵梯度法制备苹果酸舒尼替尼脂质体并对制备工艺进行考察。方法:采用混合离子交换树脂建立跨膜硫酸铵[ammonium sulfate,(NH4)2SO4]梯度制备苹果酸舒尼替尼脂质体;阳离子交换树脂分离-可见分光光度法测定苹果酸舒尼替尼脂质体的包封率,激光散射粒径分析仪测定苹果酸舒尼替尼脂质体的粒径。结果:苹果酸舒尼替尼脂质体包封率大于96%,平均粒径为107.5 nm。结论:以(NH4)2SO4梯度法制备的苹果酸舒尼替尼脂质体包封率较高,方法简便易行。     

Microcalorimetric investigation of the toxic action of ammonium ferric(III) sulfate on the metabolic activity of pure microbes

A series of calorimetric experiments were performed to investigate toxic action of ammonium ferric sulfate (AFS) on Bacillus subtilis, Pseudomonas putida and Candida humicola. The power–time curves of micro-organism metabolism were obtained, and the action of them by addition of AFS was studied. C. humicola, B. subtilis and P. putida were inhibited completely when the concentrations were up to 320.0, 160.0 and 160.0 μg mL⁻¹, respectively. The relationships between growth rate constant (k) and doses of AFS were approximately linear for three microbes, P. putida for 10.0–160.0 μg mL⁻¹ (R = −0.9746), B. subtilis for 0–160.0 μg mL⁻¹ (R = −0.9868) and C. humicola for 10.0–320.0 μg mL⁻¹ (R = −0.9955). The total heat dissipated per milliliter (Q_T) for three microbes remained balance approximately during the lower doses, P. putida and B. subtilis less than the dose of 20.0 μg mL⁻¹, 0.56 ± 0.01 and 0.26 ± 0.01 J mL⁻¹, respectively, C. humicola less than the dose of 40.0 μg mL⁻¹, 0.58 ± 0.03 J mL⁻¹. The biomass and OD₆₀₀ of three micro-organisms growth in the absence of AFS also were obtained. The power–time curve of C. humicola growth coincided with its turbidity curve. It elucidates that microcalorimetric method agreed with the routine microbiology method.     

Inhalation of ammonium sulfate and ammonium nitrate adversely affect sperm function

Among the components of air pollution in developing countries and Asia, (NH₄)₂SO₄ and NH₄NO₃ are known as major water-soluble in-organic compounds that cause particulate matter. Several researchers have been reported that the (NH₄)₂SO₄ and NH₄NO₃ induce abnormal decreases in body weight, as well as pneumotoxic, and immunotoxic. Moreover, while it has been reported that (NH₄)₂SO₄ and NH₄NO₃ have detrimental effects on reproduction, specific effects on male fertility have not been addressed in depth. Therefore, the present study evaluated the reproductive toxicity of (NH₄)₂SO₄ and NH₄NO₃ in spermatozoa under the capacitation condition. Results showed that various sperm motion parameters were significantly altered after inhalation of (NH₄)₂SO₄ and NH₄NO₃. In particular, alterations to a range of motion kinematic parameters and to capacitation status were observed after capacitation. In addition, protein kinase A (PKA) activity and tyrosine phosphorylation were altered by (NH₄)₂SO₄ and NH₄NO₃ regardless of capacitation. Taken together, our results show that inhalation of (NH₄)₂SO₄ and NH₄NO₃ may induce adverse effects on male fertility such as sperm motility, motion kinematics, and capacitation status via unusual tyrosine phosphorylation by abnormal PKA activity. Therefore, we suggest that exposure to (NH₄)₂SO₄ and NH₄NO₃ should be highlighted as a health risk, as it may lead to male reproductive toxicity in humans and animals.     

电导法测定空白脂质体硫酸铵梯度

目的建立空白脂质体硫酸铵梯度的测定方法,为确定透析方案提供科学依据。方法分别测定透析液以及脂质体总电导率,并对该方法进行线性、精密度、回收率等考察。结果该方法线性回归方程为Y=3.404×10-1c+0.278 7,硫酸铵浓度在0.1~1.5 mmol.L-1内线性关系良好(r=0.997 8),该方法日内、日间精密度均小于2%,回收率在98.7%~102.0%之间。结论该方法可用于空白脂质体硫酸铵梯度的定量测定。     

硫酸铵梯度法制备莫西沙星脂质体的工艺研究

目的 制备具有较高包封率和载药量且体外放置稳定的莫西沙星脂质体。方法 采用硫酸铵梯度法制备包载莫西沙星的脂质体,以粒径及其分布和包封率、载药量为指标对处方和工艺进行优化。结果 最佳制备条件为：空白脂质体中硫酸铵质量浓度70 mg/mL、磷脂质量浓度50 mg/mL、脂质体粒径120 nm左右、透析时间5 h、载药时药脂比2∶3、孵育温度40 ℃、孵育时间30 min。制备得到的莫西沙星脂质体粒径为（143.00±3.98）nm,包封率为（74.56±3.21）%,载药量为（26.39±1.88）%。结论 硫酸铵梯度法制备的莫西沙星脂质体包封率较高,粒径均一,室温放置稳定性良好。     

硫酸铵梯度法制备盐酸环丙沙星脂质体的影响因素

目的研究硫酸铵梯度法制备盐酸环丙沙星脂质体的影响因素。方法采用阳离子交换树脂-一阶导数分光光度法测定包封率 ,考察硫酸铵的作用及温度、药脂比对包封率的影响。结果在各种梯度法制备的盐酸环丙沙星脂质体中 ,硫酸铵梯度法得到的包封率可达 92 4 % ;盐酸环丙沙星脂质体的包封率随着硫酸铵浓度和温度的升高而增加 ,随着药脂比的增大而降低。结论硫酸铵梯度是盐酸环丙沙星脂质体包封率得以提高的主要原因 ,硫酸铵浓度、温度和药脂比是影响包封率的重要因素     

Simultaneous determination of neomycin sulfate and polymyxin B sulfate by capillary electrophoresis with indirect UV detection

A simple and rapid capillary electrophoresis method, with indirect UV detection, for the simultaneous determination of neomycin sulfate and polymyxin B sulfate in pharmaceutical formulations was developed. Critical parameters such as pH, buffer composition and concentration, voltage and injection time have been studied to evaluate, how they affect responses, such as resolution and migration times. Separation was performed on a fused silica capillary with 50 microm i.d. and 27 cm total length at an applied voltage of 6 kV with a 15 mM phosphate run buffer (pH 5.0) containing 40 mM N-(4-hydroxy-phenyl)acetamide and 50 mM tetradecylammonium bromide (TTAB). The detection wavelength was set at 280 nm. Quantitative analysis was validated by testing the reproducibility of the method, giving a relative standard deviation less than 0.4 and 2.4% for the repeatability of migration time and corrected peak area, respectively. Accuracy was tested by spiking eye-ear formulations with standards and the recoveries of neomycin sulfate and polymyxin B sulfate were found to be between 97.44-103.18% and 96.85-101.68%, respectively. Linearity of neomycin sulfate and polymyxin B sulfate were obtained in the ranges of 17-682 and 24-608 microg/mL, respectively, with r(2) values above 0.999. The established TLC-densitometric method was applied to evaluate the proposed CE method, and comparable results were obtained by using CE with much shorter analysis time and a small quantity of solvents consumed. The developed method is also the first report on the simultaneous determination of neomycin sulfate and polymyxin B sulfate in pharmaceutical preparations by CE.     

硫酸镁联合硫酸沙丁胺醇对重度支气管哮喘急性发作患儿肺功能的影响

目的 探讨硫酸镁联合硫酸沙丁胺醇对重度支气管哮喘急性发作患儿肺功能的影响.方法 选择本院2015年1月至2016年6月期间收治的60例重度支气管哮喘急性发作患儿作为观察对象,随机分为观察组和对照组,每组30例.对照组采用硫酸沙丁胺醇治疗,观察组予以硫酸镁联合硫酸沙丁胺醇治疗,治疗1周后比较两组治疗效果、康复指标(哮鸣音、气短、咳嗽)、住院时间、肺功能指标[最大呼气流量(PEF)、1秒用力呼气容积(FEV1)、用力肺活量(FVC)]与不良反应.结果 观察组总有效率为96.67％,显著高于对照组的70.00％,差异有统计学意义(x 2=7.680,P＜0.05);治疗后与对照组相比,观察组哮鸣音消失时间[(1.04±0.35)d]、气短消失时间[(2.11±1.25)d]、咳嗽消失时间[(3.75±1.08)d]及住院时间[(5.28±1.53)d]均较短,差异均有统计学意义(均P＜0.05);两组治疗前的肺功能指标比较差异均无统计学意义(均P＞ 0.05);治疗后两组FEV1、PEF、FVC水平均显著升高,且观察组上升趋势更为显著,差异均有统计学意义(均P＜ 0.05);两组患儿不良反应发生率比较差异无统计学意义(x 2=0.267,P＞0.05).结论 与单纯采用硫酸沙丁胺醇治疗重度支气管哮喘急性发作相比,硫酸镁联合硫酸沙丁胺醇治疗效果更加确切,且不良反应较少,对改善患儿临床症状与肺功能均具有积极作用,值得临床进一步推广应用.     

Evaluation of the reproductive and developmental toxicity of aluminium ammonium sulfate in a two-generation study in rats

Aluminium ammonium sulfate (AAS) was tested for reproductive/developmental toxicity in a two-generation study. Male and female rats were continuously given AAS in drinking water at 0, 50, 500 or 5000 ppm. Water consumption was decreased in all AAS-treated groups, and the body weight of parental animals transiently decreased in the 5000 ppm group. In either generation, no compound-related changes were found in estrous cyclicity, sperm parameters, copulation, fertility and gestation index, number of implantations and live birth pups, sex ratios of pups or viability during the preweaning period. Male and female F1 pups in the 5000 ppm group showed a lower body weight on postnatal day 21, while there were no differences in the birth weight of F1 and F2 pups between the control and AAS-treated groups. Preweaning body weight gain in F2 males and females indicated a similar decreasing tendency at 5000 ppm. In F1 and F2 weanlings, the weight of the liver, spleen and thymus decreased at 5000 ppm, but no histopathological changes were found in these organs. In F1 females in the 5000 ppm group, vaginal opening was delayed slightly. There were no compound-related changes in male preputial separation or in other developmental landmarks. In behavioral tests conducted for F1 animals at 4-6 weeks of age, no compound-related changes were found in spontaneous locomotor activity and performance in a water-filled multiple T-maze. In conclusion, the NOAEL of AAS for two-generation reproductive/developmental toxicity was considered to be 500 ppm in rats. Considering the aluminium content in the basal diet, the total ingested dose of aluminium from drinking water and food in this 500 ppm group was calculated to be 5.35 mg Al/kg bw/day.