几种中药材的化学成分及其定性定量检测方法研究

本论文由四部分组成。第一部分报道了佛手参提取物的化学成分研究，建立了活性成分含量测定的高效液相测定和指纹图谱研究，采用液质联用技术鉴定了主要色谱峰；第二部分报道了丹参及其复方制剂的特征图谱研究；第三部分探讨了两面针生物碱的电喷雾质谱裂解规律，并采用液质联用技术分离鉴定了提取物中的多种生物碱。第四部分概述了液质联用在药物代谢研究中的运用。 第一部分包括第一、第二和第三章。第一章针对佛手参（Gymnadeniaconopsea）块茎的甲醇提取物，采用大孔树脂和反相硅胶柱层析等各种分离方法，共分离鉴定出4 个化合物，通过波谱分析将它们的结构确定为dactylorhin B (1)、loroglossin (2)、dactylorhin A (3)和militarine (4)。这4 个化合物均是首次从佛手参中分离得到的琥珀酸葡萄糖苷类成分。第二章采用高效液相色谱法对西藏、四川、河北、青海和尼泊尔等不同地区产的十个佛手参样品进行腺嘌呤核苷和对羟基苯甲醇的定量分析，结果表明这2 个成份可视为佛手参的特征成分，但也注意到产地不同该2 个特征成分的含量也有所不同。第三章采用标准中药指纹图谱相似度计算软件，以10 个佛手参样品HPLC 图谱的平均值为相似性评价对照模板，对10 个样品进行了相似度评价，并经液质联用分析指认了7 个共有峰，分别为腺嘌呤核苷(1)、对羟基苯甲醇(2)、对羟基苯甲醛(3) 、dactylorhin B(4) 、loroglossin(5)、dactylorhin A(6)和militarine(7)。 第二部分包括第四、第五、第六和第七章。第四章运用电喷雾质谱检测了对照药材和五个不同产地的丹参药材中脂溶性和水溶性成分，系统地探讨了多种成分的电喷雾质谱规律，并以对照药材为标准建立了特征指纹图谱。五个产地的药II材通过与对照药材相对比，采用聚类分析的方法，得到了定性的鉴别与判断。并采用液质联用技术对丹参药材提取液中的化学成份进行分析，推测了九个特征峰，并对六样品的液相色谱图进行了聚类分析。第五章探讨了三七皂苷的电喷雾质谱电离和裂解规律，并采用电喷雾质谱法对三七标准药材，血通片中的皂苷成分进行了分析。第六章运用电喷雾质谱研究复方丹参片提取液的特征图谱，并和单味药材丹参和三七的特征图谱进行了对比研究。并运用HPLC-ESI MSn 分析鉴定了复方丹参片提取液中的化学成分，推测了12 个色谱峰。第七章总结了电喷雾质谱和液质联用技术在丹参药材，三七药材及复方丹参制剂中的运用的优势和局限性。 第三部分（第八章）研究了两面针生物碱中二氢白屈菜红碱(1)、二氢两面针碱(2)、8-酮基二氢白屈菜红碱(3)、8-丙酮基二氢两面针碱(4)、两面针碱(5)、和1,3-二(8-二氢两面针碱)丙酮(6)等六个苯并菲啶型生物碱的电喷雾质谱裂解规律，其中二氢两面针碱和二氢白屈菜红碱，8-丙酮基二氢两面针碱和8-酮基二氢白屈菜红碱是两对二个甲氧基分别在C-9 和C-10，C-10 和C-11 的同分异构体。实验结果表明，在相同的碰撞能下，这类位置异构体的ESI MS2 质谱二级碎片离子的相对峰度存在很大差异，这可以用于区分该类同分异构体，采用液-质联用可以对两面针的总生物碱提取物中的这些同分异构体加于区分。同时在本实验采用的液相色谱条件下，多种生物碱得到较好的分离，通过和对照品的保留时间，紫外吸收光谱及电喷雾质谱图对照，鉴定了11 个主要色谱峰。 第四部分（第九章）对液质联用技术在药物代谢中的运用进行了综述。 This dissertation consisted of four sections. The first two sections elaborated thephytochemical investigation of the rhizomes Gymnadenia conopsea R. Br., methoddevelopment for rapid identifying and qutifying the chemical condtituent of thistibetant medicine, and the chemical fingerprint analysis of rhizomes of G. conopsea,Salviae miltiorrhiza and P. notoginseng. The third section studied the fragmentationmechanism of six alkaloids from Zanthoxylum nitidium and method development forrapid identifying varieties of alkaloids from the extract of this herbal medicine. Thefourth section reviewed HPLC- MS method in drug metabolism studies. The first section consisted of chapters 1, 2, 3. Chapter 1 elaborated the phytochemicalinvestigation of Gymnadenia conopsea R. Br. Four succinate derivative esters wereisolated from the methanol extract of the rhizomes of G. conopsea through repeatedcolumn chromatography on normal and reversed phase silica gel, their structures weredetermined by ESI-MS, 1D and 2D NMR evidence. They were firstly discoveredfrom this species. In chapter 2, a high-performance liquid chromatography.diodearray detection (HPLC-DAD) method has been firstly developed for quantitation oftwo characteristic constituents, adenosine and 4-hydroxybenzyl alcohol, from theextract of rhizomes of G. conopsea. All 10 samples of G. conopsea contained differentamount of adenosine and 4-hydroxybenzyl alcohol. Adenosine and the4-hydroxybenzyl alcohol can be applied in identification and quality control for theroots of G. conopsea. In chapter 3, a high-performance liquid chromatography.diodearray detection.tandem mass spectrometry (HPLC-DAD-MSn) method has been firstly developed for chemical fingerprint analysis of rhizomes of G. conopsea andrapid identification of major compounds in the fingerprints. Comparing the UV andMS spectra with those of authentic compounds, seven main peaks in the fingerprintswere identified as adenosine, 4-hydroxybenzyl alcohol, 4-hydroxybenzyl aldehyde,dactylorhin B, loroglossin, dactylorhin A and militarine. The Computer AidedSimilarity Evaluation System for Chromatographic Fingerprint of TraditionalChinese Medicine (CASES) was employed to evaluate the similarities of 10 samplesof the rhizomes of G. conopsea collected from Sichuan, Qinghai and Hebei provincesand Tibet autonomous region of China, and Nepal. These samples from differentsources had similar chemical fingerprints to each other. The second section consisted of chapters 4, 5, 6 and 7. In chapter 4，both thecharacteristic spectra of liposoluble tanshinones and aqueous-soluble salvianolic acidswere established by the electrospray ionization mass spectrometry (ESI MS)technique and the differences between standard and crude rhizomes of Salviaemiltiorrhiza Bge. from 5 sources were analyzed. The law of electrospray ion trap mass(ESI ITMS) of typical tanshinones and salvianolic acids is studied.The analysis of the chemical constituent of rhizomes of Salviae miltiorrhiza Bge. byliquid chromatography coupled with mass spectrum (LC/MS) technique wasestablished，and the distances among standard herb and crude herb from 5 sourceswere calculated by clustering analysis. According the DAD spectra and MS2 data，9tanshinones could be speculated. In chapter 5, the character spectra of total saponinsin P. notoginseng extracts were established by ESI ITMS and selective ion monitoring(SIM) technology. The law of notoginsenosides by ESI MS2 was studied. In chapter 6,the characteristic spectra of Compound Danshen Tablet established and compared byESI-MS and HPLC/DAD/MS, 6 known tanshinones and 3 saponins were speculated.In chapter 7, the advantage and disadvantage of the strategy, using the ESI ITMS andLC/MS techniques for study of characteristic spetra of danshen and Compound Danshen Tablet, were summerized. The third section (chapter 8) studied the fragmentation mechanism of six alkaloids,dihydronitidine, dihydrochelerythrine, 8-acetonyl dihydronitidine,8-acetonyldrochelerythrine, nitidine and 1,3-bis (8-dihydronitidinyl)-acetone, by ESIMSn. Tandem mass spectrometry experiments indicated that different substitutionsites of the methoxyl groups at C-9 and C-10 or at C-10 and C-11 determined thedifferent abundances of the MS2 fragmentation ions using the same collision energy.According to the different abundances of MS2 product ions, positional isomericbenzo[c] phenanthridine alkaloids can be differentiated. Moreover, ten constituents inthe crude alkaloids extract from the roots of Zanthoxylum nitidium were rapidlyidentified by high-performance liquid chromatography coupled with tandem massspectrometry (HPLC-MSn), through comparing the retention times and ESI MSn spectra with the authentic standards. The fourth section (chapter 9) is a review on HPLC-MS method development in drug metabolism studies.

水体质量综合评价的物元模型

对水体的可拓性做了充分地分析和研究,说明了利用可拓学方法对水体质量进行分析评价的适宜性。并且应用可拓学的理论和方法,对水体的物征和质量特性进行了全面分析,建立了相应的物元模型,为水体的质量评价提供了一种新的科学方法。

科学饲喂原理与方法——如何提高饲料利用率

主要从家畜营养、生态角度出发 ,围绕如何提高饲料利用率问题 ,重点讲述了饲料生产和家畜饲养两个环节中应注意的问题 ,包括 :饲料营养中负组合效应的消除 ,毒物和抗营养因子的消除 ;鉴于草食动物的特殊性 ,饲养中就如何控制瘤胃发酵阐述了改变饲养程序、水平和日粮成分 ,用活性剂补充日粮 ,非蛋白氮的有效利用和过瘤胃技术 ;最后是如何减轻家畜冷热应激等。

陕北丘陵沟壑区苹果优质丰产栽培体系研究

园址选择、优良品种搭配、坡地改良、合理施肥与抗旱栽培、合理修剪等是陕北丘陵沟壑区苹果优质丰产的保障 ,且同时论述了各项措施的操作依据和方法

黄土高原沟坡地土地生产力评价的指标体系与评价方法

通过对渭北黄土高原地区沟坡地土壤理化性质的分析和对当地社会经济状况的调查研究,应用层次分析法对沟坡地上地自然生产力和现实生产力进行了分析和评价。在分析过程中,把当地主要造林树种根系垂直分布特征及其根系抗旱性特性纳入了分析评价体系。结果表明,嘴头村和西坡村不同树种沟坡地上刺槐(Robinia pseudoacacia)的自然生产力属于中等稍微偏上水平,而山杏(Prunus armeniacia var.ansu)、油松(Pinus tabulaeformis)和侧柏(Platycladus orientalis)的自然生产力水平则较低。两地沟坡地上的现实生产力计算结果则证明刺槐和山杏两个树种表现出了较高的水平,具有较好的发展前途;而油松和侧柏的现实生产力水平则较低,其发展推广受到了限制。群众对沟坡开发治理的态度和对开发方案的认可对沟坡开发的成功起到了重要作用。

黄土高原小流域雨水资源化潜力计算与评价初探

针对黄土高原地区水资源严重短缺的态势和生态环境建设的需要 ,以小流域为单元 ,以雨水资源为研究对象 ,在分析不同雨水利用形式的基础上 ,提出雨水资源化理论潜力、可实现潜力和现实潜力三种不同潜力 ,并探讨了小流域雨水资源化潜力的计算原理和办法 ,结合设立在黄土高原的11个国家攻关试验区小流域 ,初步提出雨水资源开发利用程度的评价办法。

陕北黄土高原可持续发展评价研究

通过对陕北黄土高原可持续发展评价指标体系和方法的初步研究 ,设计出了包括 1个高级综合指标——可持续发展综合指数、人口状况等 5个基本指标和人口自然增长率等 30个元素指标的层次性指标体系结构框架 ,熵技术支持下确定可持续发展指标权重的层次分析法 ,以及由递阶多层次综合评价、主成份分析和回归分析等数学方法所集成的可持续发展全面综合评价模型 ,并依次对该地区可持续发展现状及趋势进行了全面分析评价

大型铰接并联六维测力平台摩擦建模

在已有制造工艺及标定技术基础上,为进一步改善大型铰接并联六维测力平台的测量精度,本文基于螺旋理论和影响系数原理,引入符号函数建立了Stewart结构大型铰接六维测力平台的摩擦模型。文中提出了关节摩擦对铰接并联六维测力平台测量精度的影响矩阵及I、H类误差表达式,绘制了在不同外载和关节摩擦系数条件下,六维测力平台的I、II类误差曲线,并总结丁关节摩擦和平台自重对测力平台测量精度的影响规律。为具有普通球形铰链人型Stewart平台六维测力下台精度的提高和改善提供了理论基础。

基于评价选择策略的Internet多机器人协作控制研究

针对Internet多机器人系统中存在的操作指令延迟、工作效率低、协作能力差等问题,提出了多机器人神经元群网络控制模型。在学习过程中,来自不同功能区域的多类型神经元连接形成动态神经元群集,来描述各机器人的运动行为与外部条件、内部状态之间复杂的映射关系,通过对内部权值连接的评价选择,以实现最佳的多机器人运动行为协调。以互联网足球机器人系统为实验平台,给出了学习算法描述。仿真结果表明,己方机器人成功实现了配合射门的任务要求,所提模型和方法提高了多机器人的协作能力,并满足系统稳定性和实时性要求。

并联结构六维力传感器性能分析与优化设计

基于螺旋理论和空间模型理论绘制了Stewart平台型六维力传感器的性能图谱,总结了结构参数对传感器各性能指标的影响规律;在此基础上对大型Stewart平台六维力传感器的结构进行了非线性单目标、多目标优化设计,为具有普通球形铰链大型Stewart平台六维力传感器的设计和优化提供了依据。

基于IP QoS技术的网络机器人遥操作研究

针对基于 Internet机器人遥操作中存在的问题 ,结合 Internet网络技术的最新发展 ,借助 IP Qo S技术的特点和优势 ,本文研究并设计了基于集成业务体系结构的网络机器人遥操作系统 .通过分析 IP Qo S技术和机器人遥操作技术相互结合的可行性与合理性 ,表明该系统能够克服目前在 Internet遥操作过程中存在的问题并可在未来支持 IP Qo S技术的 Internet中发挥作用 .本文提出了该系统的设计原型及实现方法 .

基于初等运动的多机器人避碰及死锁预防

该文以一实际应用为背景提出了多移动机器人避碰及死锁预防算法 ,该算法将机器人的运行环境形式化地描述为初等运动集、冲突图、总任务集及机器人作业集 ,利用集合论、图论的有关方法及技术实现了多机器人间的避碰与死锁预防 .当机器人的运行环境改变时 ,只需要对相应的集合描述文件进行修改 ,而不用对程序做任何改动 .算法的另一个特点是利用避碰算法巧妙地完成了死锁预防 .仿真和实际运行证明了该算法高效可靠 .

基于惯性摆的波浪能获取机理与方法研究

随着陆地战略资源日益短缺以及经济的全球化进展，海洋资源的开发利用已成为沿海各国的重要发展战略之一，也成为地球资源保护与开发的关注热点。 海洋资源开发和利用能力对于一个国家的科研、经济实力具有重大的影响及意义。由于海洋资源开发利用和地球环境监测的迫切需求，促进了水下机器人、水下潜器等无人水中移动载体技术的发展。能源供给技术是水中移动载体系统的关键技术，能源技术对海洋人工系统的生存、作业、自主能力提升具有重要意义。目前海洋移动人工系统主要依赖自携带能源形式，针对水中移动载体的能量自补给技术研究还处于探索阶段。 地球表面有70%的面积被海水所覆盖，海水中蕴藏巨大的波浪能。具有环保、再生特色的波浪能开发利用技术长期以来一直受到国内外科研人员的关注。随着海洋战略地位的提升，海洋自主人工系统已成为海洋科学技术的重点发展内容。利用波浪能为海洋人工移动载体进行能量补给，是对于海洋波浪能利用的一种新的方法和思路。这对于提高海洋人工系统的自主生存、续航能力，提高人类在海洋资源与环境的探测、开发利用等方面的技术能力无疑具有重大意义。因而研究面向海洋人工系统的波浪能利用机理和系统实现技术无疑具有广泛的应用前景。 本文针对海洋人工移动载体自主能量获取利用这一重大科学技术需求，依托中国科学院基地创新基金项目“基于惯性摆原理的无源系统研究”，探索基于惯性摆机理的移动载体波浪能自主获取的机理，研究相关设计理论和技术方法。 由于目前尚无基于惯性摆机理的海洋移动载体能量自补给技术的相关研究成果。因而本论文的研究主要从理论分析和实验方法两个方面开展。重点分析了惯性摆的外激励能量获取机理，基于惯性摆的波浪机械能获取理论的可行性；开展了惯性摆载体的水动力学建模，原理样机的仿真，频域下的能量建模和优化，非线性波浪条件模拟，惯性摆载体的能量获取结构优化等研究工作。主要研究工作如下： 1.针对基于惯性摆机理的移动载体随机波能获取研究方案，分析了相关单摆及惯性摆机械能量转换机理，采用动量及动量矩定理，构建了惯性摆载体的六自由度运动学和动力学方程。 2．进行了相关水动力系数获取方法研究，获得了水动力系数数学描述。同时，采用虚拟样机方法进行惯性摆载体能量获取的研究，证明了基于惯性摆的波能自主获取方法的可行性及有效性。 3.针对虚拟样机方法建模的复杂性及容易产生错误等问题，进行了基于BP神经网络方法的惯性摆能量吸收效率的建模研究。并研究了基于该模型的不同波向角及波浪频率、载体外形尺寸、质量等的虚拟样机的波浪能吸收效率问题，为载体机构的改进及设计提供了较好的理论模型和基础。 4.开展了频域下惯性摆能量吸收效率研究。研究了基于频域的单惯性摆载体的动力学建模方法以及载体结构优化方法，提出采用多种群遗传算法进行载体结构的优化设计方法。通过仿真实验证明了相关算法的有效性，为系统的优化设计研究提供了理论基础。 5.以能量吸收效率最大为目标，进行了多种惯性摆形式的能量获取最大化分析研究，提出了包括单摆在内的多种可行的形式，给出了对比研究结果，可根据不同的提取形式而确定采用的惯性摆的形式。 6.采用PM谱对非线性波浪进行了模拟，研究了单惯性摆结构在非线性波浪力下的能量获取情况，仿真结果表明，在非线性条件下获取的惯性摆能量要更多，而其他波向角、频率等优化条件均与线性条件下的研究结果相同。

高阶广义屏波动方程叠前深度偏移

Attaining sufficient accuracy and efficiency of generalized screen propagator and improving the quality of input gathers are often problems　of wave equation presack depth migration,　in this paper,a high order formula of generalized screen propagator　for one-way wave equation is proposed by using the asymptotic expansion of single-square-root operator. Based on the formula，a new generalized screen propagator is developed ,which is composed of split-step Fourier propagator and high order correction terms，the new generalized screen propagator not only improving calculation precision without sharply increasing the quantity of computation，facilitates the suitability of generalized screen propagator to the media with strong lateral velocity variation.　As wave-equation prestack depth migration is sensitive to the quality of input gathers, which greatly affect the output，and the available seismic data processing system has inability to obtain traveltimes corresponding to the multiple arrivals, to estimate of great residual statics， to merge seismic datum from different projects and to design inverse Q filter, we establish　difference equations with an embodiment of Huygens’s principle for obtaining traveltimes corresponding to the multiple arrivals,bring forward a time variable matching filter for seismic datum merging by using the fast algorithm called Mallat tree for wavelet transformations， put forward a method for estimation of residual statics by applying the optimum model parameters estimated by iterative inversion with three organized algorithm,i.e,the CMP intertrace cross-correlation algorithm,the Laplacian image edge extraction algorithm,and the DFP algorithm, and present phase-shift inverse Q filter based on Futterman’s amplitude and phase-velocity dispersion formula and wave field extrapolation theory. All of their numerical and real data calculating results shows that our theory and method are practical and efficient. Key words: prestack depth migration, generalized screen propagator, residual statics，inverse Q filter ,traveltime，3D seismic datum mergence

胜利勘探数据中心及勘探辅助决策系统研究

In the paper through extensive study and design, the technical plan for establishing the exploration database center is made to combine imported and self developed techniques. By research and repeated experiment a modern database center has been set up with its hardware and network having advanced performance, its system well configured, its data store and management complete, and its data support being fast and direct. Through study on the theory, method and model of decision an exploration decision assistant schema is designed with one decision plan of well location decision support system being evaluated and put into action. 1. Study on the establishment of Shengli exploration database center Research is made on the hardware configuration of the database center including its workstations and all connected hardware and system. The hardware of the database center is formed by connecting workstations, microcomputer workstations, disk arrays, and those equipments used for seismic processing and interpretation. Research on the data store and management includes the analysis of the contents to be managed, data flow, data standard, data QC, data backup and restore policy, optimization of database system. A reasonable data management regulation and workflow is made and the scientific exploration data management system is created. Data load is done by working out a schedule firstly and at last 200 more projects of seismic surveys has been loaded amount to 25TB. 2. Exploration work support system and its application Seismic data processing system support has the following features, automatic extraction of seismic attributes, GIS navigation, data order, extraction of any sized data cube, pseudo huge capacity disk array, standard output exchange format etc. The prestack data can be accessed by the processing system or data can be transferred to other processing system through standard exchange format. For supporting seismic interpretation system the following features exist such as auto scan and store of interpretation result, internal data quality control etc. the interpretation system is connected directly with database center to get real time support of seismic data, formation data and well data. Comprehensive geological study support is done through intranet with the ability to query or display data graphically on the navigation system under some geological constraints. Production management support system is mainly used to collect, analyze and display production data with its core technology on the controlled data collection and creation of multiple standard forms. 3. exploration decision support system design By classification of workflow and data flow of all the exploration stages and study on decision theory and method, target of each decision step, decision model and requirement, three concept models has been formed for the Shengli exploration decision support system including the exploration distribution support system, the well location support system and production management support system. the well location decision support system has passed evaluation and been put into action. 4. Technical advance Hardware and software match with high performance for the database center. By combining parallel computer system, database server, huge capacity ATL, disk array, network and firewall together to create the first exploration database center in China with reasonable configuration, high performance and able to manage the whole data sets of exploration. Huge exploration data management technology is formed where exploration data standards and management regulations are made to guarantee data quality, safety and security. Multifunction query and support system for comprehensive exploration information support. It includes support system for geological study, seismic processing and interpretation and production management. In the system a lot of new database and computer technology have been used to provide real time information support for exploration work. Finally is the design of Shengli exploration decision support system. 5. Application and benefit Data storage has reached the amount of 25TB with thousand of users in Shengli oil field to access data to improve work efficiency multiple times. The technology has also been applied by many other units of SINOPEC. Its application of providing data to a project named Exploration achievements and Evaluation of Favorable Targets in Hekou Area shortened the data preparation period from 30 days to 2 days, enriching data abundance 15 percent and getting information support from the database center perfectly. Its application to provide former processed result for a project named Pre-stack depth migration in Guxi fracture zone reduced the amount of repeated process and shortened work period of one month and improved processing precision and quality, saving capital investment of data processing of 30 million yuan. It application by providing project database automatically in project named Geological and seismic study of southern slope zone of Dongying Sag shortened data preparation time so that researchers have more time to do research, thus to improve interpretation precision and quality.