中药质量控制技术发展展望

本文从中药产业需求、现代化需求、技术需求、机遇与挑战等方面概括了中药质量控制技术发展的背景;讨论了中药质量控制技术对于提高中药药效和安全性、推动产业发展和推进中药国际化的意义;综述了中药质量控制技术的现状,分析了在过程控制、安全性控制、标准品和对照品制备、指纹图谱技术等方面的不足;提出了中药质量控制技术应重点发展以分离和表征技术为主的中药质量控制关键技术、中药安全性控制技术、中药质量控制标准体系、中药质量控制原创性技术和中药标准品、对照品生产技术,制定技术标准,建立具有中药特色的过程控制和产品质量控制标准。     

高分辨质谱技术在中药分析中的研究进展

中药分析涉及中药物质基础研究、药物代谢、中药质量控制等多个领域,是中药现代化研究的基础。随着现代化分析技术的发展,中药分析研究取得了极大的进展。针对中药成分复杂、代谢过程多样、目标物浓度低等难点,高分辨质谱技术凭借精确质量数、高分辨率及高灵敏度的优点在中药分析中具有显著优势。该文对高分辨质谱技术在中药分析中的应用进行了综述,重点介绍了四极杆飞行时间质谱、静电场轨道阱质谱、傅里叶变换离子回旋共振质谱和离子淌度串联质谱等质谱技术的发展,以及高分辨质谱在中药化学成分鉴定、中药化合物代谢研究、中药植物代谢组学研究以及中药有害化学成分检测中的研究进展。同时,对高分辨质谱在中药分析中的应用进行了展望,以期促进中药现代化发展。     

中药指纹图谱学体系在中药创制中的作用

从整体论、系统论和复杂科学的角度论述了中药指纹图谱学体系的构成背景和核心任务。中药指纹图谱学体系具有体系科学性质,是从系统性和整体性角度研究中药(包括植物药)的物质基础和作用机制以及药代动力学规律和相关制剂技术的崭新学科。该体系以中药指纹图谱信息学为核心和桥梁,包括中药指纹图谱测试学、中药指纹图谱质控学、中药指纹图谱谱效学、中药指纹药物动力学、中药指纹药剂学和中药生物指纹图谱学。该体系的研究需采用复杂科学和体系科学的理论和方法,突破线性思维和还原分析,强调宏观和系统的有机综合,应用数学科学原理和方法来开辟中药创制的新模式。中药指纹图谱学的理论体系和方法是解析中药的主导技术和实现中药现代化的核心力量,该体系理论和技术的成熟及完善可为现代中药创制提供强有力的理论和技术支撑。中药指纹图谱学体系的最终目的是为人类和有益生物研制出疗效显著、安全、可控的现代化中药。     

新书《中药指纹学》简介

<正>国家要求仿制与原研药须杂质谱一致、稳定性一致、体内外溶出规律一致。中药物质基础复杂、多数组分尚未明确,所以中药一致性评价有其特殊性。中药指纹图谱是实现整体鉴别中药真实性、评价质量一致性和产品稳定性的可行模式,可用于中药质量一致性评价。中药指纹学(TCM fingerprintothology)是以现代分析技术、中药学、中药化学、中药药理学、化学计量学和计算机科学等学科为依托,用系统性和整体性的方法研究中药(植物药)的物质基础、作用机     

中国的中药微量元素研究 Ⅲ.微量元素：中药性效量化的物质基础

综述了中药四气、五味以及中药功效与微量元素的量化关系。中国中药微量元素研究结果表明,中药微量元素含量水平是决定中药性味的主要因素之一,也是判定中药功效的重要物质基础。     

“中药质量控制”专栏引言

中药在中国有着几千年的临床使用经验。随着民众对药品有效性和安全性认识的加深,中药质量受到越来越多的重视,中药质量控制也随之成为保障中药产业发展的重要因素之一和中药现代化研究的重要内容之一。由于中药的复杂性、多样性和物质基础研究的局限性,中药质量控制技术的发展成为中药质量控制的关键。     

引言

中药在中国有着几千年的临床使用经验。随着民众对药品有效性和安全性认识的加深,中药质量受到越来越多的重视,中药质量控制也随之成为保障中药产业发展的重要因素之一和中药现代化研究的重要内容之一。由于中药的复杂性、多样性和物质基础研究的局限性,中药质量控制技术的发展成为中药质量控制的关键。随着中药物质基础、药理活性研究的深入和现代分离分析技术对复杂体系分析能力的提高,中药质量控制水平有了明显的提高;在认识到中药药效是多靶点、多成分的协同作用特点后,多指标成分定量成为中药含量测定的发展趋势。近年来,着重于从整体上进行质量控制的指纹图谱技术得到了广泛的关注和应用,并已被国外认可,成为建立国际性中药质量标准的技术纽带。各种色谱、光谱技术在指纹图谱中的运用及利用现代分离和检测技术获取海量数据,使人们对于中药的认识达到了一个新的高度。海量数据的化学计量学分析更成为鉴别中药真伪、优劣的科学依据。
中药质量控制是一个不断认识和深入的过程,新问题、新理念和新技术的层出不穷为我们提出了一个又一个的新课题。随着研究的深入,各方面的研究成果将为中药质量控制提供更为丰富的科学依据,中药质量控制技术也必然随着中药整体研究水平的提高而发展,并为中药的现代化和国际化做出巨大贡献。由于色谱技术在中药质量控制中发挥了巨大作用,本刊特别邀请了部分具有突出贡献的色谱专家、学者撰写了相关学术论文,在本期编辑出版了“中药质量控制”专栏。希望通过这些专栏文章所介绍的工作及思想,广集思路,不断创新,为进一步提高中药质量控制的研究水平作出贡献。     

中药组方指纹图谱研究方法和思路

中药组方就是将单味中药按照一定的规律配伍成方,因剂量配伍差异会导致组方理化性质的改变,从而导致组方功效强弱、性质方面发生变化,甚至产生新的化学成分。中药组方鉴别与质量控制一直是困扰中药工作者的一个难题。指纹图谱技术具有宏观、准确、稳定等优点,已被广泛用于中药领域。中药组方指纹图谱是解决中药合理组方配伍的最有效手段,其对中药质量控制已经得到普遍关注和重视。由于指纹图谱具有整体定量功能和特征性鉴别作用,对于成分复杂的中药组方能够全面地定性与定量评价。本文就中药组方指纹图谱的研究意义与目的进行了综述,并详细阐述了组方指纹图谱的研究方法与思路,以此为中药及其组方指纹图谱研究提供参考。     

中药质量评价关键问题与分析方法探讨

该文针对我国目前中药质量评价体系现状,总结了中药质量评价的关键科学问题,并围绕"发现"与"控制"有效成分的中药质量评价方法进行探讨.笔者结合多年中药质量分析研究工作经验,分析了中药"谱-效"关系研究、全时段等基线多波长融合指纹图谱、生物活性测定法3种质量评价与检测方法的研究内容、手段、适用范围等,为丰富、完善中药质量控...     

电化学分析方法在中药质量控制中的研究进展

中药质量控制是保证中药现代化、产业化以及国际化的核心问题。与其它分析方法相比,电化学分析法具有灵敏度高、检测速度快和成本低等优点,是中药质量控制的重要手段,具有广阔的发展前景。本文综述了近年来电化学方法在中药质量控制方面的研究进展,介绍了电化学指纹图谱技术在中药鉴别方面的研究概况,着重归纳了电化学技术在分析中药有效成分和有害物质中的应用,包括黄酮类、生物碱类、醌类、苷类、重金属和农药残留等,并展望了电化学方法在中药质量控制领域的发展前景。     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

衬底上石墨烯制备及改性研究

大面积高质量石墨烯的制备对石墨烯电子特性及石墨烯基纳器件相关研究有重要意义。本文综述了近几年来衬底上制备石墨烯的相关实验以及衬底与石墨烯相互作用研究的重要进展。目前,采用化学气相沉积、外延生长等方法可在衬底表面上制备出较大面积、高质量的石墨烯材料。衬底与石墨烯相互作用和界面间晶格匹配、原子成键及电荷转移等密切相关,其对吸附石墨烯的几何结构、能带结构及电子特性等产生明显影响。实验与理论计算的结合可望加深衬底与石墨烯作用机理的理解,指导衬底上石墨烯制备及改性的进一步研究。     

Acidity,lipophilicity, solubility,absorption, and polar surface area of some ACE inhibitors

Computational chemical methods have been used to correlate the molecular properties of the 10 ACE inhibitors (captopril, enalapril, perindopril, lisinopril, ramipril, trandolapril, quinapril, fosinopril, benazepril, and cilazapril) and some of their active metabolites (enalaprilat, perindoprilat, ramiprilat, trandolaprilat, quinaprilat, fosinoprilat, benazeprilat, and cilazaprilat). The computed pK _a values correlate well with the available experimental values. In the dicarboxylic ACE inhibitors, the carboxyalkyl carboxylate group of the ACE inhibitors studied is more acidic than the C-terminal carboxylate. However, at physiological pH = 7.4 both carboxyl groups of ACE inhibitors are completely ionized and the dicarboxyl-containing ACE inhibitors behave as strong acids. The available experimental partition coefficients of these ACE inhibitors investigated are well reproduced by the neural network-based ALOGPs and the fragment-based KoWWiN methods. All parent drugs (and prodrugs), with the exception of fosinopril, are compounds with low lipophilicity. Calculated pK _a, lipophilicity, solubility, absorption, and polar surface area of the most effective ACE inhibitors for the prevention of myocardial infarction, perindopril and ramipril, were found similar. Therefore, it is probable that the experimentally observed differences in the survival benefits in the first year after acute myocardial infarction in patients 65 years of age or older correlate closely to the physicochemical and pharmacokinetic characteristics of the specific ACE inhibitor that is used.     

Elemental Characterization of Ciders and Other Low-Percentage Alcoholic Beverages Available on the Polish Market

Seventy-three samples of alcoholic beverages and juices that were purchased on the Polish market and home-made were analyzed for their elemental profiles. The levels of 23 metals were determined by ICP-MS (Ag, Ba, Bi, Cd, Co, Cr, Li, Mn, Ni, Pb, Sr and Tl), ICP-OES (Al, B, Ca, Cu, Fe, K, Mg, Na, Ti and Zn) and CVAAS (Hg) techniques in twenty-five samples of ciders widely available on the Polish market; six samples of home-made ciders; two samples of juices used in the production of these ciders; and forty samples of low-percentage, flavored alcoholic beverages based on beer. The gathered analytical data confirmed that the final elemental fingerprint of a product is affected by the elemental fingerprint of the ingredients used (apple variety) as well as the technology and equipment used by the producer, and in the case of commercial ciders, also the impact of type of the packaging used was proven. These factors are specific to each producer and the influence of the mentioned above parameters was revealed as a result of the performed analysis. Additionally, the inclusion of the home-made ciders in the data set helped us to understand the potential origin of some elements, from the raw materials to the final products. The applied statistical tests revealed (Kruskal–Wallis and ANOVA) the existence of statistically significant differences in the concentration of the following metals: Ag, Al, B, Bi, Co, Cr, Cu, Fe, K, Li, Mg, Na, Ni, Ti and Zn in terms of the type of cider origin (commercial and home-made). In turn, for different packaging (can or bottle) within one brand of commercial cider, the existence of statistically significant differences for Cu, Mn and Na was proved. The concentrations of all determined elements in the commercial cider from the Polish market and home-made cider samples can be considered as nontoxic, because the measured levels of elements indicated in the regulations were lower than the allowable limits. Moreover, the obtained results can be treated as preliminary for the potential authentication of products in order to distinguish the home-made (fake) from the authentic products, especially for premium-class alcoholic beverages.     

An integrated strategy of secondary metabolomics and glycomics to investigate multi-component variations in wine-processing of medicinal herbs and functional foods: A case study on Fructus Corni

Fructus Corni (FC), as a promising Chinese medicinal herb, has aroused considerable interest. Generally, FC needs to be processed according to the limited standard policy in China before clinical application, while the investigations on the specific processing methods (such as wine steaming or high-pressure wine steaming) are unclear. A comprehensive metabolomics strategy based on integrated non-targeted metabolomics and targeted glycomics in this paper was implemented to investigate the influences of the different processing technologies such as steaming, wine steaming, high-pressure steaming, high-pressure wine steaming, wine immersion, and wine stir-frying on FC, respectively. UHPLC-Q-TOF-MS/MS was employed for identifying and distinguishing the secondary metabolites. A total of 85 components were identified in all groups. The results of PCA score plots showed that the crude and processed samples had a complete separation, and wine steamed and high-pressure wine steamed samples could be a category, indicating that the two processed products had a similar quality. Multiple chromatography including HPLC (C₁₈)-PDA, HPLC (NH₂)-ELSD, and HPGPC-ELSD was used for determining the molecular weight distributions, the monosaccharide compositions of polysaccharides, and the contents of free monosaccharides and oligosaccharides. The results indicated that the content and composition of saccharides were different in crude and different processed FC. The polysaccharides were composed of fucose, arabinose, galactose, glucose, galacturonic acid, mannose and rhamnose, and the free monosaccharides were composed of fucose, arabinose, galactose, glucose, mannose, rhamnose and fructose in all FC samples. The PCA score plots of the glycomics indicated that the crude and high-pressure wine steamed FC could be a category, showing that the two groups had similar chemical compositions. Ultimately, the simulation processing experiments indicated that the transformation of morroniside, polysaccharides, oligosaccharides, fructose, and glucose to 5-HMF through the reactions of dehydration and deglycosylation was the potential mechanism of enhancing the effects by processing. Conclusionly, the saccharides should be investigated as thoroughly as the secondary metabolites, and the high-pressure wine steamed FC could be an alternative to wine steamed FC.     

Self-Assembling Drug Formulations with Tunable Permeability and Biodegradability

This review focuses on key topics in the field of drug delivery related to the design of nanocarriers answering the biomedicine criteria, including biocompatibility, biodegradability, low toxicity, and the ability to overcome biological barriers. For these reasons, much attention is paid to the amphiphile-based carriers composed of natural building blocks, lipids, and their structural analogues and synthetic surfactants that are capable of self-assembly with the formation of a variety of supramolecular aggregates. The latter are dynamic structures that can be used as nanocontainers for hydrophobic drugs to increase their solubility and bioavailability. In this section, biodegradable cationic surfactants bearing cleavable fragments are discussed, with ester- and carbamate-containing analogs, as well as amino acid derivatives received special attention. Drug delivery through the biological barriers is a challenging task, which is highlighted by the example of transdermal method of drug administration. In this paper, nonionic surfactants are primarily discussed, including their application for the fabrication of nanocarriers, their surfactant-skin interactions, the mechanisms of modulating their permeability, and the factors controlling drug encapsulation, release, and targeted delivery. Different types of nanocarriers are covered, including niosomes, transfersomes, invasomes and chitosomes, with their morphological specificity, beneficial characteristics and limitations discussed.     

Diffusion of symmetrical and spherical solutes in protic,aprotic, and hydrocarbon solvents

The diffusion coefficients of a series of symmetrical tetraalkyltins (tetramethyltin, tetraethyltin, tetrapropyltin, tetrabutyltin, tetradodecyltin) of the gases argon, krypton, xenon, methane, and tetramethylmethane and of carbon tetrachloride and tetraethylmethane in hexane, decane, and tetradecane at 25°C have been determined using the Taylor dispersion technique. Diffusion coefficients for the gases in acetone, 2-propanol, 1-butanol, and 1-octanol were also determined. Deviations from the predictions of Stokes' law were found to be large, and the magnitude of the deviation can be directly related to solute size. The predictions of the Hubbard-Onsager equation were tested using the diffusion data.     

MISCIBILITY AND MORPHOLOGY OF THIN FILMS OF BLENDS OF POLYSTYRENE WITH BROMINATED POLYSTYRENES： EFFECTS OF VARYING THE MOLECULAR WEIGHT, BROMINATION DEGREE AND ANNEALING

Thin films of incompatible polymer blends can form a variety of structures during preparation and subsequent annealing process. For the polymer blend system consisting of polystyrene and poIy(styrene-co-p-bromo-styrene), i.e., PS/PBrxS, its compatibility could be adjusted by varying the degree of bromination and the molecular weight of both components comprised, in this paper, surface chemical compositions of the cast and the annealing films were investigated by X-ray photoelectron spectroscopy (XPS) and contact angle measurement; meanwhile, surface topographical changes are followed by atomic force microscopy (AFM). In addition, substantial attention was paid to the effect of annealing on the morphologic variations induced by phase separation and/or dewetting of the thin film. Moreover, the influences of the molecular weight, Aw, as well as the brominated degree, x%, on the sample surface are explored systematically, and the corresponding observations are explained in virtue of the Flory-Huggins theory, along with the dewetting of the polymer thin film.     

多极性基有机添加物对非离子表面活性剂溶液雾点的影响

测定了甲酸、乙酸、草酸、甲醇、乙醇、丙醇、乙二醇、丙三醇和葡萄糖对非离子表面活性剂Triton X-100和Triton X-114水溶液雾点的影响。低级脂肪酸和醇能使雾点升高, 升高的程度随酸或醇的碳氢链的增长而增加。但若在增加分子碳氢链长或碳氢部分的同时引入更多的羧基或羟基, 则雾点升高的效应将受到抑制。当极性基数目较多时, 可导致雾点显著下降。     

Multi-Elemental Analysis as a Tool to Ascertain the Safety and the Origin of Beehive Products: Development,Validation, and Application of an ICP-MS Method on Four Unifloral Honeys Produced in Sardinia,Italy

Despite unifloral honeys from Sardinia, Italy, being appreciated worldwide for their peculiar organoleptic features, their elemental signature has only partly been investigated. Hence, the principal aim of this study was to measure the concentration of trace and toxic elements (i.e., Ag, As, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Li, Mn, Mo, Ni, Pb, Sb, Sn, Sr, Te, Tl, V, and Zn) in four unifloral honeys produced in Sardinia. For this purpose, an original ICP-MS method was developed, fully validated, and applied on unifloral honeys from asphodel, eucalyptus, strawberry tree, and thistle. Particular attention was paid to the method’s development: factorial design was applied for the optimization of the acid microwave digestion, whereas the instrumental parameters were tuned to minimize the polyatomic interferences. Most of the analytes’ concentration ranged between the relevant LoDs and few mg kg⁻¹, while toxic elements were present in negligible amounts. The elemental signatures of asphodel and thistle honeys were measured for the first time, whereas those of eucalyptus and strawberry tree honeys suggested a geographical differentiation if compared with the literature. Chemometric analysis allowed for the botanical discrimination of honeys through their elemental signature, whereas linear discriminant analysis provided an accuracy level of 87.1%.