组分中药色谱分离方法学研究

Presently, Traditional Chinese Medicine (TCM) is an important resource to treat many diseases, which has a long history in China, and is very complicated in chemical composition and pharmacology. Therefore, modernization of TCM is very necessary, including standardization, resourcing, quality control and research on chemical composition and pharmacology. “Multi-Component Chinese Medicine (MCCM)” represents a specific group of chemical composition produced from TCM according to a standardized separation process, which is hopefully to discover the chemical fundament of TCM’s pharmacology. The systematic research on MCCM is basing on modern separation and analytical techniques. In our group, a high-throughput preparation method has been developed in order to accelerate the pharmacological study of MCCM. The whole of TCMs were separated into a serious of small fractions containing several compounds by high-throughput preparative chromatography. Then these small fractions, what is called screening multi-components (SMCs), were screened by high-throughput screening (HTS). After biological screening, active multi-components were obtained and could be studied deeply further. This method will accelerate the process of explanation of the curative mechanism of TCMs, which simplifies the complex TCMs by concentrating on those interesting compounds from hundreds of thousands of compounds in TCMs. Standard libraries of SMCs are constructed, which will not only satisfy the need of TCMs, but also will speed up drug discovery by supplying persistent source for HTS. Two-dimensional liquid chromatography (2DLC) systems have developed for the characterization of SMCs and preparation of active compounds. Orthogonality and compatibility between the two-dimensional separations are key factors affecting the development of 2DLC. Based on the development of novel stationary phases, RP-HILIC 2DLC system and RP-RP 2DLC system were established.Two-dimensional liquid chromatography (2DLC) systems have developed for the characterization of SMCs and preparation of active compounds. Orthogonality and compatibility between the two-dimensional separations are key factors affecting the development of 2DLC. Based on the development of novel stationary phases, RP-HILIC 2DLC system and RP-RP 2DLC system were established

一种葛根有效组分的制备方法

本发明提供了一种葛根有效组分的制备方法，将葛根药材粉碎后加水提取，先后经50％～80％乙醇醇沉，10000～25000Ram/min高速离心后，非极性大孔吸附树脂上样，乙醇/水洗脱，收集洗脱液并浓缩干燥后得葛根大孔树脂组分，再经工业制备色谱柱分离，甲醇水作流动相，即得葛根有效组分。其主要的活性成分是葛根素，3′-甲氧基葛根素和葛根素芹菜糖苷，其总含量达到93.8％。本发明制备的葛根有效组分中葛根素的含量＞50％，有效的去除糖蛋白、多糖、氨基酸等杂质，提高了主要活性成分的含量。制备过程重复性高和可操作性好，易于实现标准化和产业化，同时对于葛根药材的质量控制也有一定的指导意义。带填

基于定量指纹图谱技术的中药质量控制

定量指纹图谱技术是中药指纹图谱技术与多指标成分定量分析相结合的中药质量控制模式。定量指纹图谱技术的发展包括定量组分的制备、过程控制的指纹图谱技术和产品含量测定3个主要部分。本文以丹参为例,通过水提、醇沉、过膜、大孔树脂分离和工业色谱分离5个工艺流程制备了丹参定量组分,对各个工艺步骤以指纹图谱技术考察其稳定性和重复性。对丹参定量组分中的原儿茶醛、迷迭香酸、丹酚酸B3个成分进行含量测定。3个成分的含量总和大于50%。定量组分的制备以现有的活性成分为目标,经过去粗存精的工艺过程,其质量标准得到了有效的提高

中药标准组分制备与组分库的构建

本研究通过对多种现代分离技术的集成，构建了中药系统分离制备的标准化平台，并制定了一系列标准操作规范控制提取分离过程。通过平台运行，已完成了50味中药和8个复方的1100多个标准组分的分离制备，建立了一定规模的标准组分库和相应的标准操作规范。初步形成了中药标准组分库，为中药物质基础研究和创新中药研发提供了丰富的组分资源

一种糖键合硅胶固定相及其制备方法

本发明涉及液相色谱固定相，键合相为单糖，二糖，或寡糖(聚合度为 3-10)，其结构为：其中，X为-OCH3或-OCH2CH3，Y为-OH或-NH2Ac，n＝1～10。首先在硅胶表面引入叠氮基团，制备叠氮基硅胶中间体；然后通过叠氮基与炔基的1， 3-环加成反应，即click chemistry，在水溶液中20～80℃的条件下反应24～72 小时，将炔基糖分子键合到叠氮基硅胶表面。本发明提供的色谱分离材料结构新颖，柱效和分离选择性高。该固定相用作液相色谱分离材料能在亲水色谱模式下对强极性化合物有很好的保留和分离的效果，特别适合用于分离和分析强极性化合物。带填

Chromatographic Methodology and Technology for Developing TCM

Chromatographic Methodology and Technology for Developing TC

黄芪水提取物对apoe小鼠动脉粥样硬化斑块部位基质金属蛋白酶9表达及斑块形成的影响

目的探讨黄芪水提取物对载脂蛋白E基因敲除(ApoE-/-) 小鼠主动脉粥样硬化斑块部位基质金属蛋白酶-9(MMP-9)表达及斑块形成的影响。 方法将48只8周龄雄性ApoE-/-小鼠给予高脂饮食喂养，小鼠20周龄时根据随机表按照完全随机法分为4组各12只,即对照组、阿托伐他汀组、黄芪水提取物低剂量组及黄芪水提取物高剂量组。对照组给予生理盐水0.2 ml/d，阿托伐他汀组给予阿托伐他汀10 mg·kg~(-1)·d~(-1)，黄芪水提取物低剂量给予黄芪水提取物 1.25 g·kg-1·d-1、黄芪水提取物高剂量给予黄芪水提取物 5 g·kg-1·d-1灌胃。予给药12周末处死各组小鼠。应用ELISA法测定血清氧化低密度脂蛋白（oxLDL）含量；HE染色、油红O染色观察小鼠主动脉粥样斑块内脂质的形成；用免疫荧光、免疫组化染色法检测观察粥样斑块部位巨噬细胞浸润水平及MMP-9表达。 结果黄芪水提取物明显降低ApoE-/-小鼠，其中黄芪水提取物高剂量组血清oxLDL含量明显低于对照组（5.2±6.1）μg/ml比（15.8±5.4）μg/ml，P<0.01；与对照组比较，黄芪水提取物高剂量组ApoE-/-小鼠动脉粥样斑块面积明显减小（17.24%±4.22%比49.87%±9.37%，P<0.01），动脉管壁斑块弥漫程度较轻(P<0.01)。黄芪水提取物高剂量组斑块中Mac3表达低于对照组(P<0.01)；黄芪水提取物高剂量组与对照组主动脉斑块中MMP-9阳性表达面积平均吸光度值(MA)分别为0.0154±0.0014与0.0263±0.0065 (P<0.01）。 结论黄芪水提取物能够抑制ApoE-/-小鼠动脉MMP-9表达，延缓动脉粥样硬化斑块形成。其机制可能是通过降低ApoE-/-小鼠血清oxLDL水平，抑制巨噬细胞的浸润、迁移及分泌MMP-9，从而抑制斑块形成

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel

JUNO sensitivity on proton decay p → ν K + searches*

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the $p\to \bar{\nu} K^+$ mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar{\nu} K^+$ is 36.9% ± 4.9% with a background level of $0.2\pm 0.05({\rm syst})\pm$$0.2({\rm stat})$ events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is $9.6 \times 10^{33}$ years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies