γ-亚麻酸甲酯制备与二高-γ-亚麻酸甲酯合成方法的改进

本文报导:(1)以石油醚为介质,采用催化量甲醇的工艺,改进了已有的甲醇-尿素法制备较高纯度的γ-亚麻酸,适合于大规模制备,提得率及纯度均提高。(2)以复合硼氢化物代替四氢锂铝还原γ-亚麻酸甲酯,再经氯化亚砜-丙二酸酯法或甲磺酰氯-丙二酸酯法制备二高-γ-亚麻酸甲酯,得到较满意结果。     

γ-亚麻酸甲酯包合物的制备及热稳定性研究

目的制备γ-亚麻酸甲酯包合物并考察其热稳定性。方法用饱和水溶液法制备γ亚麻酸甲酯β-环糊精的固体包舍物,用红外光谱和γ-射线衍射技术分析包合物的主-客体分子闯相互作用及晶相结构,用热重分析技术考察包合物的热性质。结果γ-亚麻酸甲酯与β-环糊精可以形成摩尔比为1：3的包合物,实现了γ-亚麻酸甲酯粉末化,提高了γ-亚麻酸甲酯的热稳定性：结论包合物可以提高γ-亚麻酸甲酯的热稳定性。     

γ-亚麻酸甲酯乳剂代谢动力学

本文应用动物全血、组织匀浆体外保温实验和大鼠离体肝脏灌流技术研究了γ-亚麻酸甲酯乳剂的代谢动力学。γ-亚麻酸甲酯在全血中迅速水解;在肝、小肠和肾中也存在代谢;离体肝灌流液中γ-亚麻酸的浓度下降与时间关系经拟合符合单指数方程,消除半衰期为13.2min,肝固有消除率为2.46ml/min.     

γ-亚麻酸甲酯乳剂小肠吸收动力学研究

本文采用大鼠在、离体小肠吸收实验，并结合体内法对γ－亚麻酸甲酯乳剂（γ－ＬＡＭＥ）的小肠吸收进行研究。γ－ＬＡＭＥ吸收率为８５％；胆管结扎与不结扎吸收率无显著性差异；其吸收机制属被动扩散．γ－ＬＡＭＥ大鼠幽门静脉及灌胃给药，其生物利用度分别为７４．４％及９２％．     

γ—亚麻酸甲酯乳剂小肠吸收动力学研究

本文采用大鼠在、离体小肠吸收实验，并结合体内法对γ－亚麻酸甲酯乳剂（γ－ＬＡＭＥ）的小肠吸收进行研究，γ－ＬＡＭＥ吸收率为８５％；胆管结扎与不结扎吸收率地显著性差异；其吸收机制属被动扩散，γ－ＬＡＭＥ大鼠幽门静脉及灌胃给药，其生物利用度分别为７４．４％及９２％．     

γ-亚麻酸甲酯纳米乳的制备及质量评价

目的研制γ-亚麻酸甲酯纳米乳制剂并对其进行质量评价。方法优选γ-亚麻酸甲酯纳米乳剂处方,评价制剂的结构、形态、分散性及稳定性。结果以聚乙二醇400作助表面活性剂,当表面活性剂聚山梨酯80与γ-亚麻酸甲酯质量比为1∶2时,制得了γ-亚麻酸甲酯纳米乳剂,γ-亚麻酸甲酯在乳剂中含量为25%。γ-亚麻酸甲酯纳米乳在透射电镜下呈圆球形,平均粒径为60 nm,室温保存6个月后纳米乳分散均匀且稳定好。结论获得了性质稳定的γ-亚麻酸甲酯纳米乳,为开发γ-亚麻酸注射剂奠定了基础。     

γ—亚麻酸甲酯乳剂代谢动力学

本文应用动物全血、组织匀浆体外保温实验和大鼠离体肝脏灌流技术研究了γ－亚麻酸甲酯乳剂的代谢动力学。γ－亚麻酸甲酯在全血中迅速水解；在肝、小肠和肾中也存在代谢；离体肝灌流液中γ－亚麻酸的浓度下降与时间关系经拟合符合单指数方程，消除半衰期为１３．２ｍｉｎ，肝固有消除率为２．４６ｍｌ／ｍｉｎ。     

高纯度γ-亚麻酸及其衍生物的制备

本文道了运用硝酸银柱层析法分离得到纯度为98%的γ-亚麻酸甲酯。合成了几个γ-亚麻酸衍生物。实验初步结果表明,它们具有抑制由ADP诱导的血小板凝聚的作用。     

γ-亚麻酸乙酯的合成研究

目的确定合成γ 亚麻酸乙酯的最佳工艺路线。方法以黑加仑油为原料采用尿素包和、柱色谱法、酸催化法等联合方法分离及合成γ 亚麻酸乙酯。结果确定黑加仑油经 2～ 3次尿素包和 ,反应温度 80℃ ,反应时间90min ,3%盐酸作酸性溶媒 ,乙醇和γ 亚麻酸比例为 3∶1的制备工艺。结论酸催化法合成γ 亚麻酸乙酯工艺简便 ,易于操作 ,产品收率高、稳定性好。     

合成前列腺素E_1的中间体-γ亚麻酸甲酯的制备

以r-亚麻酸甲酯为原料可合成二高-r-亚麻酸,再经生物合成得前列腺素E_1。本文报道了由月见草(Oenothera biennis)种子油制备 r-亚麻酸甲酯的方法。所得产品为无色或微带黄色的油状液体,含有 r-亚麻酸60%(GLC)以上。按月见草油计算,总收率约3%。     

A new sesquiterpene lactone glycoside and a new quinic acid methyl ester from Patrinia villosa

A new sesquiterpene lactone glycoside (1) and a new quinic acid methyl ester (2) were isolated from Patrinia villosa, together with another two known compounds chlorogenic acid n-butyl ester (3), 3, 4-di-O-caffeoylquinic acid methyl ester (4). Their structures were established using 1D/2D-NMR spectroscopy, mass spectrometry, and comparing with spectroscopic data reported in the literature.     

4-Aminobutyric acid methyl ester hydrochloride,a precursor of 4-aminobutyric acid

4-Aminobutyric methyl ester hydrochloride (GME) is able to cross the blood-brain barrier after intracardiac administration to the rat. GME has an LD₅₀ of 1300 mg/kg in mice and 950 mg/kg in rats, exhibits an antiaggressive effect and is able to decrease isoniazid-induced convulsions in the rat. GME is hydrolyzed to 4-aminobutyric acid (GABA) by brain homogenates, acts as an inhibitor of GABA binding to crude synaptic plasma membranes, activates the release and inhibits the uptake of GABA by rat synaptosomes and acts as a competitive inhibitor of the so-called GABAse system in vitro.     

不同生长期独一味中山栀苷甲酯和8-O-乙酰山栀苷甲酯的含量研究

目的:研究分析不同生长期独一味中山栀苷甲酯和8-O-乙酰山栀苷甲酯含量。方法:采用HPLC反相色谱柱Waters Symmetry C18(5μm,4.6 mm×250 mm),梯度洗脱[0~10 min,乙腈-水(10∶90);10~30 min,乙腈-水(18∶82)],流速1.0mL.min-1,检测波长235 nm,柱温25℃。结果:不同生长期的独一味中山栀苷甲酯和8-O-乙酰山栀苷甲酯的总含量有明显差异,从6月份到9月份呈近似于正态分布的趋势,以7月中旬到8月初期间的含量为最高。结论:本方法结果准确,重现性好,易于操作,可用于不同生长期独一味中山栀苷甲酯和8-O-乙酰山栀苷甲酯的含量研究。     

白花蛇舌草2种主要香豆酸类化学成分的含量测定

目的建立同时测定白花蛇舌草中(E)-6-0-P-香豆酰鸡屎藤苷甲酯和香豆酸的方法。方法采用反相高效液相色谱法,Kromasil ODS柱(4.6 mm×250 mm,5μm),乙腈-0.1%冰醋酸梯度洗脱(0 min,20∶80;30 min,30∶70;35 min,60∶40)。检测波长:303 nm,柱温30℃,流速1 mL.min-1。结果白花蛇舌草中(E)-6-0-P-香豆酰鸡屎藤苷甲酯和香豆酸在该条件下有较好的线性关系,当提取溶剂不同时,两者的提取率有较大差异。结论测定方法简便、准确,为白花蛇舌草质量控制提供了可靠的依据;不同提取溶剂试验研究对确立白花蛇舌草最佳提取工艺有一定的参考价值。     

依他尼酸甲酯诱导人急性髓性白血病HL-60细胞凋亡作用和机制的初步探讨

目的研究依他尼酸甲酯(EAME)对人急性髓性白血病HL-60细胞的凋亡诱导作用,并初步探讨EAME诱导HL-60细胞凋亡的机制。方法采用吖啶橙(AO)、溴化乙啶(EB)双染法考察药物的凋亡诱导活性;采用流式细胞术检测活性氧的蓄积和线粒体膜电位的变化;利用荧光标记法检测细胞内还原型谷胱甘肽(GSH)含量的变化。结果EAME浓度在2~10μmol.L-1内对HL-60细胞具有显著的凋亡诱导能力;EAME诱导活性氧蓄积,降低线粒体膜电位和细胞内GSH含量;N-乙酰半胱氨酸(NAC)能够完全逆转EAME对GSH水平的耗竭作用及对HL-60细胞的凋亡诱导作用;丁硫氨酸亚砜胺(BSO)可以协同EAME进一步降低细胞内GSH水平,同时增强凋亡诱导能力。结论EAME可诱导HL-60细胞发生凋亡,活性氧在凋亡诱导过程中起主要作用。细胞内GSH水平与细胞对EAME诱导凋亡的敏感性呈反向相关。     

Similar effects of succinic acid dimethyl ester and glucose on islet calcium oscillations and insulin release

The relative contribution of glycolysis vs. oxidative metabolism to the stimulus secretion coupling mechanism of beta-cells was investigated in isolated islets. For that purpose, the secretory and intracellular calcium responses of islets to both glucose and succinic acid dimethyl ester (SAD) were compared. After 45 min of rat islet perifusion in the absence of substrates, the maximum secretory responses to glucose (20 mmol/L) and SAD (10 mmol/L) were qualitatively and quantitatively indistinguishable. Malonic acid dimethyl ester (a permeable citric acid cycle inhibitor) suppressed the insulin secretory response to both 20 mmol/L glucose and 10 mmol/L SAD (-70% on average). The inhibitor decreased within 70% the rate of 14CO2-production from 10 mmol/L [2-(14)C]pyruvate without affecting the rate of 20 mmol/L D-[5-(3)H]glucose utilization. Both, 11.1 mmol/L glucose and 10 mmol/L SAD, elevated the intracellular calcium concentration and induced a similar pattern of oscillations that were rapidly ablated by 20 mmol/L malonic acid dimethyl ester. However, the intracellular concentration of calcium declined to basal values several minutes after the introduction of the inhibitor in the presence of SAD whereas it remained elevated in the case of glucose. In conclusion: (1) An exclusive increase of mitochondrial metabolism in pancreatic islets was sufficient to mimic the effects of glucose on intracellular calcium and insulin secretion. (2) Islet glycolysis and/or the re-oxidation of cytoplasmic NADH allowed the maintenance of an elevated, though non-oscillating, intracellular calcium concentration, but a reduced response to glucose.     

工作场所空气中丙烯酸甲酯等6种有害物质气质联用同时测定方法的研究

目的 建立一种高效实用快速的工作场所空气中丙烯酸甲酯等6种有害物质气质联用同时测定方法.方法 用活性碳管采样,二硫化碳解吸,气质联用法检测.结果 方法简便、高效、快速、准确、灵敏度高.加标回收率(解吸率)＞98.0%.结论 本法测定丙烯酸甲酯等6种有害物质,其检测结果均能符合中华人民共和国国家职业卫生标准所规定的相关要求.     

几丁糖酯抗动脉粥样硬化作用研究

用高脂膳食喂养家兔建立动脉粥样硬化模型,观察几丁糖酯对脂质代谢及主动脉斑块形成的影响,结果表明,几丁糖酯可以降低家兔血清中甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）及丙二醛（MDA）含量,升高高密度脂蛋白胆固醇（HDL-C）,减轻肝脏脂肪样变,砬轻主动脉斑块形成程度;在体外培养牛主动脉平滑肌细胞,观察几丁糖酯对细胞增殖的影响。结果表明,几丁糖酯可抑制血管平滑肌细胞增殖。透射电镜观察,给药组细胞呈现收缩型的形态学特征,而对照组则呈现合成型的特征。     

左旋多巴甲酯对斜视性弱视猫模型的作用

目的观察左旋多巴甲酯对斜视性弱视猫视皮质c-fos基因表达的影响,探讨盐酸左旋多巴甲酯对弱视的治疗作用及其作用机制。方法正常幼猫30只随机分成6组:左旋多巴甲酯低剂量、中剂量和高剂量组、模型对照组、阳性对照组及正常对照组,每组5只,于4wk时行眼外直肌切除术造成人工斜视(正常对照组除外),经图形视觉诱发电位(P-VEP)确定形成弱视后,灌胃给予左旋多巴甲酯20,40,80mg·kg-1,阳性对照组给予左旋多巴40mg·kg-1,正常对照组及模型组均给予等量生理盐水。观察P-VEP的变化并采用原位杂交技术检测各组猫视皮质的c-fosmRNA表达情况。结果左旋多巴甲酯明显的缩短猫斜视性弱视眼的P100波峰潜时及提高P100波幅值。斜视猫视皮质的阳性染色细胞较正常猫减少,差异有显著性(P<0.01),用药后各组阳性染色细胞较模型对照组明显增加(P<0.01)。结论左旋多巴甲酯明显地改善斜视性弱视猫模型弱视眼的传导和感觉功能,其机制可能与左旋多巴甲酯进入脑内的量增加及介导视皮质c-fos mRNA的表达调控有关。     

Inhibition of erythrocyte aldehyde dehydrogenase activity and elimination kinetics of diethyldithiocarbamic acid methyl ester and its monothio analogue after administration of single and repeated doses of disulfiram to man

Summary The elimination kinetics of the methyl esters of diethyldithiocarbamic acid (Me-DDC) and its monothio analogue (Me-DTC) has been compared in ten alcoholic patients after a single oral dose of 400 mg disulfiram (Antabuse). Erythrocyte aldehyde dehydrogenase (ALDH) activity was continuously followed in the subjects until complete inactivation.The relation between individual steady-state concentrations of Me-DTC in plasma, blood acetaldehyde concentration and the dose of disulfiram sufficient to give the disulfiram alcohol reaction was investigated in 12 healthy volunteers treated with increasing doses of disulfiram and then challenged with ethanol.The mean peak plasma concentration of Me-DDC occurred at 1.8 h and its plasma half-life was 6.3 h. The corresponding values for Me-DTC were 3.3 h and 11.2 h, respectively. This suggests oxidative formation of Me-DTC from Me-DDC. In alcoholics with a rapid decrease in erythrocyte ALDH activity (in less than 5 days), the mean peak plasma concentration of Me-DTC was 278 nmol·l^–1, whereas the peak concentration was below the detection limit in subjects with a prolonged inactivation time (7–20 days).The healthy volunteers were divided into three groups of four subjects, with clinically valid disulfiram alcohol reactions at 100, 200, and 300 mg doses of disulfiram, respectively. The mean plasma concentrations of Me-DTC at steady-state were proportional to the disulfiram doses given, compared within groups at different doses, and between groups at equal and different optimal doses of the drug. The concentrations of Me-DTC were significantly increased, as compared above, whereas the blood concentrations of acetaldehyde were not significantly increased. The increased plasma concentration of Me-DTC suggests increased oxidative transformation in those individuals, and is apparently associated with enhanced ALDH activity in hepatocytes, shown by the lower plasma concentrations of acetaldehyde, despite increased concentrations of the inhibitor.