乙醇胺的生产及应用

对乙醇胺的生产工艺，用途、国内外乙醇胺的生产状况加以介绍．对一步法生产三乙醇胺的经济效益做了分析，对乙醇胺的生产提出了建议。     

乙醇胺的生产技术

论述了乙醇胺合成的方法，介绍国外乙醇胺的先进生产技术，并结合国内乙醇胺的生产现状提出了其生产技术改造的必要性及初步设想。     

国内外乙醇胺生产现状与发展趋势

介绍了乙醇胺国内外生产现状，市场需求和发展趋势，指出我国与国外先进水平相比有较大差距，针对现状提出我国乙醇胺发展思路。     

乙醇胺二甲叉膦酸的合成

以乙醇胺、三氯化磷和甲醛为原料合成了乙醇胺二甲叉膦酸（EODMP）。对其合成条件进行了探讨，确定最佳条件为：甲醛过量50％，反应温度为100℃，回流时间3h。在优化上，产品的收率（以乙醇胺计）为91．2％。     

产品开发

乙醇胺亟待加强开发生产 我国乙醇胺主要消费领域是：表面活性剂领域占31％，医药及农药26％，聚氨酯12％，气体净化7％，以及橡胶助剂、纺织工业、金属清洗与加工等领域。由于下游产品快速发展，拉动乙醇胺需求迅猛增加。但我国乙醇胺一向供不应求，对外依存率很高。2005年我国乙醇胺表观消费量为12．9％万t，进口量8．8万t，进口依存度高达68．2％，2009年表观消费量增加至22．5万t。进口量增加至15．2万t，进口依存度仍然高达68％。预计2010年我国乙醇胺的需求量将继续增加亟待加强开发生产。     

吡罗克酮乙醇胺盐的蛋白酶抑制作用及与硫酸锌复配的防脱发功效研究（英文）

蛋白水解机制导致棒状末端发根和毛囊之间的细胞粘附分解是头发脱落的最终步骤。在休止期晚期和脱落期，蛋白酶活性的增加导致大量脱发。利用EnzChekTM蛋白酶试剂盒，基于荧光方法检测了吡罗克酮乙醇胺盐在体外对蛋白酶的抑制作用；并对含吡罗克酮乙醇胺盐和硫酸锌的洗发水进行了两组含受脱发困扰的男性和女性参与者的临床防脱发功效测试。结果表明，吡罗克酮乙醇胺盐可以有效抑制蛋白酶的活性，0.5%吡罗克酮乙醇胺盐在体外可使胰蛋白酶的活性减少最高达53%。硫酸锌可以增强低浓度吡罗克酮乙醇胺盐对胰蛋白酶活性的抑制作用。两组临床测试显示，使用含0.5%吡罗克酮乙醇胺盐和0.018%硫酸锌的洗发水4周，8周和12周后，头发密度较使用前均有显著性增加，12周后分别增加2.7根/cm²和7.5根/cm²；较空白对照组，在8周和12周后均有显著性提高。由此提示了吡罗克酮乙醇胺盐对于棒状毛发的保留作用和含吡罗克酮乙醇胺盐和硫酸锌洗发水的防脱发功效。     

用生产聚乙烯醇副产的醇解回收液合成N-乙酰乙醇胺的新方法研究

探索了一种合成N-乙酰乙醇胺的新方法，用生产聚乙烯醇过程中副产的含有醋酸甲酯的醇解回收液为原料，合成N-乙酰乙醇胺。实验结果表明，当反应温度为52℃、反应时间为8h、乙醇胺与醇解回收液中的醋酸甲酯物质的量比为2：1、有机强碱类用量与醇解回收液中醋酸甲酯的物质的量比为1：9时，N-乙酰乙醇胺的收率高迭99．8％，回收的甲醇纯度可迭99．9％，这不仅使醋酸甲酯和甲醇得到了有效的分离，而且可使醋酸甲酯用于生产高附加值的N-乙酰乙醇胺。该研究为醇解回收液找到了一种更为有效、能够带来更大的经济效益的方法。     

乙醇胺的市场及生产工艺分析

对乙醇胺的产能和市场需求做了简要的分析,并分析了中国市场的乙醇胺产能、消费及构成、扩能展望及现状,指出了中国乙醇胺生产的不足;其次还对当今乙醇胺的生产工艺进行了介绍,着重介绍了国内与国外乙醇胺生产工艺,指出了我国乙醇胺在生产工艺落后与市场需求量大的矛盾;最后对国内乙醇胺的生产提出了个人建议。     

乙醇胺的需求与生产技术

文章对乙醇胺的需求做了简要的分析,指出了我国对乙醇胺的消耗量逐年增长而国内乙醇胺的产量却远不能满足国内市场,乙醇胺进口量大;其次文中还对当今乙醇胺的生产工艺进行了介绍,着重介绍了国内现行的国产化乙醇胺生产工艺,指出了我国乙醇胺在生产工艺落后与市场需求量大的矛盾;最后文中还对国内乙醇胺的生产提出了个人建议.     

2----溴乙胺氢溴酸盐的合成研究

以乙醇胺和溴化氢为原料分两步合成了2－溴乙胺氢溴酸盐，成盐反应是在室温下，乙醇胺与48％的氢溴酸1：1条件下进行中和反应，溴化反应则是乙醇胺氢溴酸盐的乙苯溶液通入溴化氢气体，反应温度控制在130℃，反应时间为4．5小时获得了最佳反应结果，产品总收率95％。     

HPLC法测定泥土中氯硝柳胺的含量

[目的]建立测定泥土中氯硝柳胺含量的HPLC分析方法.[方法]以C18柱,流动相为甲醇-20 mol/L磷酸二氢钾溶液(含磷酸0.1%)(体积比85:15),检测波长为236 nm.[结果]方法的线性相关系数为0.9999,相对标准偏差0.8%,平均回收率为97.54%.[结论]该方法准确,可用以测定泥土中氯硝柳胺含量.     

氯硝柳胺改性灭尾蚴药物小试生产工艺的研究

对氯硝柳胺进行改性,在其羟基上接上聚乙二醇基可以大大增加氯硝柳胺在水面的表面扩散性,更有利于杀灭血吸虫尾蚴。本文主要研究了聚乙二醇基氯硝柳胺衍生物的合成小试工艺,并对小试工艺的步骤、反应过程的控制、原料的回收利用等进行了简化和优化。     

Niclosamide Suppresses Migration and Invasion of Human Osteosarcoma Cells by Repressing TGFBI Expression via the ERK Signaling Pathway

Osteosarcoma is a highly common malignant bone tumor. Its highly metastatic properties are the leading cause of mortality for cancer. Niclosamide, a salicylanilide derivative, is an oral antihelminthic drug of known anticancer potential. However, the effect of niclosamide on osteosarcoma cell migration, invasion and the mechanisms underlying have not been fully clarified. Therefore, this study investigated niclosamide’s underlying pathways and antimetastatic effects on osteosarcoma. In this study, U2OS and HOS osteosarcoma cell lines were treated with niclosamide and then subjected to assays for determining cell migration ability. The results indicated that niclosamide, at concentrations of up to 200 nM, inhibited the migration and invasion of human osteosarcoma U2OS and HOS cells and repressed the transforming growth factor beta-induced protein (TGFBI) expression of U2OS cells, without cytotoxicity. After TGFBI knockdown occurred, cellular migration and invasion behaviors of U2OS cells were significantly reduced. Moreover, niclosamide significantly decreased the phosphorylation of ERK1/2 in U2OS cells and the combination treatment of the MEK inhibitor (U0126) and niclosamide resulted in the intensive inhibition of the TGFBI expression and the migratory ability in U2OS cells. Therefore, TGFBI derived from osteosarcoma cells via the ERK pathway contributed to cellular migration and invasion and niclosamide inhibited these processes. These findings indicate that niclosamide may be a powerful preventive agent against the development and metastasis of osteosarcoma.     

聚乙二醇基氯硝柳胺衍生物体外抑制钉螺乙酰胆碱酯酶活性的研究

为研究聚乙二醇基氯硝柳胺衍生物体外抑制钉螺乙酰胆碱酯酶的活性,测定了氯硝柳胺衍生物抑制钉螺乙酰胆碱酯酶的半数抑制浓度IC50.结果表明:随着氯硝柳胺衍生物浓度的增加,对乙酰胆碱酯酶活性的抑制作用逐渐增强;随着聚乙二醇基链长的增加,药物对乙酰胆碱酯酶抑制活性依次减弱.     

农药产品中贝螺杀乙醇胺盐的高效液相色谱分析

用反相高效液相色谱法(HPLC),采用ODS-C8色谱柱,以甲醇-水-为流动相,在230nm下测定贝螺杀乙醇胺盐的含量,方法准确、可靠。     

Nitro-Deficient Niclosamide Confers Reduced Genotoxicity and Retains Mitochondrial Uncoupling Activity for Cancer Therapy

Niclosamide is an oral anthelmintic drug, approved for use against tapeworm infections. Recent studies suggest however that niclosamide may have broader clinical applications in cancers, spurring increased interest in the functions and mechanisms of niclosamide. Previously, we reported that niclosamide targets a metabolic vulnerability in p53-deficient tumours, providing a basis for patient stratification and personalised treatment strategies. In the present study, we functionally characterised the contribution of the aniline 4′-NO₂ group on niclosamide to its cellular activities. We demonstrated that niclosamide induces genome-wide DNA damage that is mechanistically uncoupled from its antitumour effects mediated through mitochondrial uncoupling. Elimination of the nitro group in ND-Nic analogue significantly reduced γH2AX signals and DNA breaks while preserving its antitumour mechanism mediated through a calcium signalling pathway and arachidonic acid metabolism. Lipidomics profiling further revealed that ND-Nic-treated cells retained a metabolite profile characteristic of niclosamide-treated cells. Notably, quantitative scoring of drug sensitivity suggests that elimination of its nitro group enhanced the target selectivity of niclosamide against p53 deficiency. Importantly, the results also raise concern that niclosamide may impose a pleiotropic genotoxic effect, which limits its clinical efficacy and warrants further investigation into alternative drug analogues that may ameliorate any potential unwanted side effects.     

新型氯硝柳胺漂浮缓释剂的制备及灭血吸虫尾蚴活性

现有的预防和控制血吸虫病措施难以从根本上控制血吸虫病。为防止人群感染血吸虫病,根据血吸虫尾蚴聚集于水面的生态特点,以氯硝柳胺为原药,锯末为载体研制出新型氯硝柳胺漂浮缓释剂,漂浮缓释剂可在水面漂浮30天不下沉,药物缓慢释放,对血吸虫尾蚴有较强的杀灭作用,有效时间超过30天。新剂型长期漂浮水面,为控制血吸虫病的蔓延提供了有效的途径。     

Niclosamide,a Drug with Many (Re)purposes

Niclosamide is an anthelmintic drug that has been used for over 50 years mainly to treat tapeworm infections. However, with the increase in drug repurposing initiatives, niclosamide has emerged as a true hit in many screens against various diseases. Indeed, from being an anthelmintic drug, it has now shown potential in treating Parkinson's disease, diabetes, viral and microbial infections, as well as various cancers. Such diverse pharmacological activities are a result of niclosamide's ability to uncouple mitochondrial phosphorylation and modulate a selection of signaling pathways, such as Wnt/β‐catenin, mTOR and JAK/STAT3, which are implicated in many diseases. In this highlight, we discuss the plethora of diseases that niclosamide has shown promise in treating.     

83.1%杀螺胺乙醇胺盐可湿性粉剂配方研究

对83.1%杀螺胺乙醇胺盐可湿性粉剂配方进行研究,并考察了该配方对不同原药的适应性。试验发现,润湿分散剂WP453、聚羧酸盐ST669与抗絮凝剂三聚磷酸钠、载体白炭黑的加入能够提高83.1%杀螺胺乙醇胺盐可湿性粉剂的悬浮率,解决制剂变色和絮凝现象,且该配方适用于不同来源的原药。所制制剂杀螺效果较好。