【作者】 赵良；

【导师】 梁国刚； 王智民；

【作者基本信息】 中国中医科学院 ， 中药学， 2011， 博士

【摘要】 在中药现代化和国际化的推进进程中,我们遭遇过系列事件的剧痛,最让人难忘的是上世纪90年代以来发生的多起中药重金属超标事件。尽管这些事件多数是出于技术性贸易壁垒的缘故,但却成了国际医药市场用以贬低中药的工具和手段,严重损害了中药的国际声誉。由此,如何解决重金属超标的难题引起了国内学者的研究和关注,其中,采用配位化学原理选择性吸附或萃取中药重金属的技术成为研究的热点和焦点。然而,由于中药有效成分复杂,在考虑剔除中药中有害元素的同时,如何尽可能保留中药的有效成分不损失或少损失成为研究的难点。为了实现选择性剔除中药重金属的目标,我们设计了一些对有害元素有选择性的络合片段结合到一定的材料上,而这个材料必须对有效成分不吸附或少吸附,硅胶恰好具备这个特征,在含水量超过17%后失去其吸附性质仅为载体(而大孔吸附树脂、活性炭等难以满足此要求),其表面的羟基可进行表面修饰。本论文采用硅烷化反应将络合片断以Si-O-Si-C化学键连接到硅胶表面(络合片断的末端为-SH、-NH2及含氮杂环等3类基团),共合成了9种键合硅胶,其中5种为已知结构的键合硅胶,4种为新结构的键合硅胶。采用了漫反射红外、元素分析、N2吸附/解吸附等温曲线测定、X射线衍射等方法对键合硅胶的结构进行了表征。结果表明,络合片断被成功的引入到硅胶的表面,且化学键合过程不会引起硅胶本身微孔结构次序的变化。在pH 1.0、4.0和6.0的缓冲溶液中,测定和比较了9种键合硅胶对11种金属离子的吸附容量。结果发现,γ-巯丙基硅胶(y-mercaptopropyl-modified silica gel, MPS)对Pb2+、Cd2+、Cu2+、Hg2+等4种重金属离子均具有较高的吸附容量,且对Fe2+、Fe3+、Mn2+等有益元素吸附容量小,符合选择性吸附重金属离子的要求。分配系数测定结果进一步显示,MPS对上述4种重金属离子具有很高的选择性。因此,选择MPS作为最佳的重金属离子吸附材料。本文以Pb2+为例,研究了MPS吸附水溶液中Pb2+的吸附规律。吸附速率快,等温吸附曲线符合Langmuir方程,最佳吸附pH为6.0,最大吸附容量为0.523 mmol·g11 (108.4 mg·g-1),使用过的MPS可用0.1 N盐酸进行再生。将MPS应用于脱除金银花药液中的铅离子,采用静态吸附和动态吸附的方式考察铅的脱除率,并以药液含固量、HPLC指纹图谱为指标,比较了脱铅过程中,药液中化学成分的变化情况。静态吸附实验表明,MPS吸附药液中铅离子的速度快,最大铅脱除率达到80%。动态吸附对铅离子的脱除效果优于静态吸附,当金银花药液中铅离子浓度为1.04μg·mL-1,最佳脱铅的工艺参数为：上样量为6 BV的药液,径高比1：10,洗脱速度6 BV.h-1,温度为25℃；脱铅过程中,药液含固量和HPLC图谱均无明显变化。将MPS应用于某“清茶复方”水提液中铅离子的脱除,结果表明,与空白硅胶(SG)比较,MPS能够明显地降低药液中铅的含量,脱除率为74.6%；脱铅过程中,水提液中化学成分变化很小,含固量损失率仅为2.6%,HPLC图谱相似度为0.976。由此判断,MPS脱铅过程中,保留了中药有效成分,选择性地剔除药液中的铅离子,实现了实验设计的目标。为了获得了工艺稳定、质量可控的MPS生产技术,本论文对该材料进行了工艺研究、质量标准研究和稳定性研究。结果表明,MPS的巯基(-SH)键合量可达到600μLmol·g-1(2.0％),稳定性研究表明室温下MPS化学性质比较稳定,表面的巯基不易被氧化。最后,本论文基于MPS吸附金银花中铅离子的规律及化学平衡的研究,并假设动态吸附过程可以转换为多个连续的静态吸附过程和塔板吸附过程,推导出描述动态吸附过程的两个表达式。其一,铅脱除率该式从理论上证明了动态吸附可以实现重金属的完全脱除(当n→∞时,铅脱除x→100%),也反映了各主要工艺种参数之间的关系。其二,WHM=WAbs×Q0/2,该式可用于估算键合硅胶的吸附能力,为确定键合硅胶的用量提供依据。本课题以键合硅胶为吸附材料,用于中药提取液中铅离子的脱除,成功地实现了保留中药有效成分,选择性剔除中药重金属的目标,为键合硅胶材料应用于中药重金属的脱除提供了示范,也为中药重金属脱除技术的开发提供一种思路和方法。更多还原

【Abstract】 In the process of modernization and internationalization of traditional Chinese medicine (TCM), we have experienced a series of misrable events, in particular, many events of heavy metals excess in TCM happened since the 1990s are impressive. Although most of these events are out of technical barriers, they indeed lead to the downgrade of TCM in international medicine market, thus affecting international reputation. Therefore, how to solve the problem of heavy metals excess triggers wide attention and research by demostic scholars, wherein the technique for selectively absorbing or extracting TCM heavey metals by using coordination chemistry principle is one of the hot spots. Since TCM effective components are complicated, we must remove the harmful elements in TCM while keeping effective components not lost or lost less. To reach this goal, chelated fragment selective for harmful elements is bonded to a certain material, and this material does not absorb effective components or absorb less. Silica gel, having this property, loses its absorption capability after water content exceeds 17%, acts as carrier only (while macroporous organic resin, active carbon and etc. can’t meet this requirement), and hydroxyl group on the silica surface can be modified.Chelated fragment is bonded on the surface of silica gel via chemical bond Si-O-Si-C by silanization reaction (the end of the chelated fragment includes-SH、-NH2 and nitro-containing heterocycle), and nine modified silica gels are synthesized, wherein five silica gels have known structures and others have new structures. The structures of the modified silica gels are characterized by FT-IR spectroscopy, elemental analysis, N2 adsorption/desorption measurement, and X-ray diffraction. The results show that chelated fragment is successfully introduced to the surface of silica gel, and the chemical bonding cause no obvious change of microcellular structure order of silica gel carrier.The adsorption capacities of the nine modified silica gels toward eleven metal ions are measured in buffering solution with pH 1.0,4.0 and 6.0 using batch equilibrium adsorption experiments. Results show that y-mercaptopropyl-modified silica gel (MPS) has high adsorption capacities toward heavy metals Pb2+, Cd2+, Cu2+, Hg2+ and low ones for beneficial elements Fe2+, Fe3+, Mn2+, meaning MPS is capable of selectively absorbing heavy metal ions. Partition ratio tests further show that MPS has preferable selectivity for the above four heavy metals, making it possible to use MPS as optimal adsorption material for heavy metal ions. Taking Pb2+ for example, the adsorption rate is fast and the adsorption isotherms fits to Langmuir equation, the optimal adsorption pH value is 6.0, the maximum adsorption capacity is 0.523 mmol·g-1 (108.4 mg·g-1), and the spent MPS can be regenerated using 0.1 N HC1. y-Mercaptopropyl-modified silica gel (MPS) is applied to remove plumbum ion from the extract of Lonicera japonica Flos. The static and dynamic adsorptions were used to investigate the removal efficiency of plumbum ion. The solid content and HPLC profiles of the extract were determined to evaluate the process changes. The static adsorption experiments show that MPS has fast adsorption rate and more than 80% removal efficiency toward plumbum ion. The dynamic adsorption has better plumbum ion removal effect than the static adsorption, when the concentration of plumbum ion in the extract of Lonicera japonica Flos is 1.04μg-mL-1, the optimum parameters were as follows:6 BV of sample volume, the optimum parameters were as follows:6 times of raw materials,10 times of height to diameter, and 6 BV·h-1 of flow velocity, at the temperature of 25℃. During the removal process, obvious changes of solid content and HPLC profiles were not observed. MPS can also be used for removing plumbum ion from extract of Qingcha compound. The results show that MPS can effectively remove plumbum, with the removal efficiency of 74.6%, compared with unmodified silica gel (SG). During the removal process, there were no obvious change of solid content (only 2.6% loss) and comparability of HPLC profiles (similarity is 0.976). Therefore, MPS can selevtively remove plumbum in TCM solution with the effective components being reserved, thus realizing the objective of the expriments.In order to get stable production process and controllable quality, the process optimization, quality standard and stability of MPS were studied. The result shows that the thiol group (-SH) content of MPS can reach 600μmol·g-1(2.0%). Stable production research test shows that MPS is stable under room temperature, and-SH on the surface is hard to be oxidized.Finally, based on the adsorption regularity of MPS for removing plumbum ion in Lonicera japonica Flos, and the assumption that the dynamic adsorption process can be converted into successive static adsorption process and plate adsorption process, expressions for dynamic adsorption process are deduced. Firstly, plumbum removal efficiency which not only proves that dynamic adsorption can remove heavy metal completely in theory (x goes to 100% while n is infinite), but also reflects the relations between main process parameters. Secondly, WHM=WAbs×Q0/2, which is used for evaluating the adsorption ability of modified silica gel, and provides foundation for dosage of modified silica gel.In this paper, modified silica gel is used as the adsorbent, for removing plumbum ion in extract of TCM. Effective components are reserved, and heavy metals are selectively removed. Hence, this paper provides an example of applying modified silica gel to TCM heavy metal removal, and also a novel method for developing TCM heavy metal removal technique.更多还原