制药与生物制药

复合维生素片剂包含了人体所需的各种矿物质，对于维护我们的健康和机能至关重要。本文介绍一种方法，用来快速、无损的对复合维生素补充剂片上的无机矿物成分进行成像。研究人员使用了 HORIBA XGT-9000 微区X射线荧光分析仪，该仪器能够在短短 20 分钟内揭示出关键无机元素在片剂上的分布情况。即使元素的浓度低至每片数十毫克甚至更少，这种方法依然能够准确地观察到元素的分布情况。

Raman imaging combined with Layers app enables rapid and non-constructive layer analysis for delayed-release formulations.

Raman spectroscopy combined with chemometric modeling enables high-throughput, non-destructive quantification of excipient composition in pharmaceutical powder blends.

Raman microscopy combined with high-throughput acquisition enables rapid, non-destructive drug qualification and chemical characterization of pharmaceutical tablets.

3D confocal Raman microscopy enables non-destructive detection and spatial localization of minor crystalline API forms within pharmaceutical extrudates, supporting comprehensive solid-state characterization.

The use of low molecular weight molecules in the industries of drug discovery and agri-food has become increasingly important over the course of a century of drug research and science development in agriculture and in pharmaceutical field.

This application highlights the development of an oligosaccharide chip (surface functionalization, density of immobilization, spacer arm length) on the same SPRi platform using conductive polymers. These results are highlighted through the example of interactions between HS and SDF-1 α chemokine.

本文展示了粒径相关的拉曼光谱技术（Particle Correlated Raman Spectroscopy, PCRS）作为一种强大手段的优势，它能将粒子特性表征与化学物质鉴定相结合，从而让我们更深入地了解药物在不同药物剂型（喷雾剂、片剂、乳膏剂）中的性能表现。

HORIBA provides the pharmaceutical industry, biotech companies and academic research laboratories with high performance instrumentation based on SPRi technology (Surface Plasmon Resonance imaging). To demonstrate the power of this technology, we carried out an experiment based on an antibody-antigen interaction. Original surface chemistry combined with an electrochemical process allows the rapid coupling of biomolecules to the gold layer (polypyrrole co-polymerisation) on the top of a glass prism.

在药物产品的研究中，颗粒特征（计数、大小和化学特征）和化合物分布（大小和空间）是决定产品质量的关键参数，因为这些属性对最终固体剂型的溶解速率（以及生物利用度）有着巨大的影响。监控这些属性对于原材料、加工过程中的中间产物和最终产品至关重要。在本应用报告内容所对应的实验使用了类似于药品混合物的粉末混合物。本文旨在展示将激光衍射技术和拉曼光谱技术联合应用在颗粒物表征方面的显著优点。

本篇应用文档报道了 TERS 表征沉积在镀金衬底上的磷脂双分子层，该样品可以用作标准样品，检测到脂质成分在纳米尺度上的分布。此外，还引入了纳米材料来模拟纳米颗粒和细胞膜之间的相互作用，帮助更好地研究纳米材料对人类健康的毒性。 TERS 检测磷脂双分子层中纳米颗粒的灵敏度可以低至飞摩尔浓度，空间分辨率低至 7 nm。还开发了一种特定的液体样品池，可以实现在溶液中进行 TERS 测量，应用文档中提供了测试氧化石墨烯样品的结果。

本文中，HORIBA 展示了来自 CPI 的评估工作，证明 A-TEEM™ 技术适用于分析单克隆抗体的六个生产工艺样品。这项研究是将该技术作为生物制药过程分析技术(PAT)解决方案进行应用的第一步。

随着行业向强化和连续处理转型，对能够在无菌且符合 GMP 条件下运行的快速实时分析工具的需求日益增长。A-TEEM™ 技术凭借其高灵敏度、分子选择性和实时数据输出特性满足这些要求，为优化细胞生长和整体生物工艺性能提供可操作的见解。

We introduced a fast and non-destructive imaging method for inorganic minerals on a multivitamin supplement tablet containing various essential minerals to body functions. We used the HORIBA XGT-9000 X-ray Analytical Microscope for the imaging, and we could visualize the distribution of the key inorganic elements on the tablet less than 20 minutes even though the concentration of the elements are tens of mg or less per tablet.

使用含醇凝胶（水醇凝胶）消毒双手已成为日常习惯。与此同时，70%浓度的酒精用于伤口消毒的历史更为悠久。然而，为确保消毒效果，这类产品的酒精浓度不得低于规定阈值，且必须受到严格管控。本应用指南阐述了如何利用拉曼光谱技术在质量控制过程中评估酒精浓度。

由于新冠病毒危机，消毒洗手液已经成为我们日常生活的一部分。然而，洗手液中含有的微塑料可能会给环境及人类健康带来风险。HORIBA 可提供微塑料分析和表征所需要的工具：高性能显微拉曼光谱仪、微塑料样品制备附件以及功能强大的颗粒分析技术 ParticleFinder™。本文使用 HORIBA 微塑料解决方案，分析了三种来自不同国家的洗手液样品，并识别出每种洗手液不同微塑料的含量。

X-ray Fluorescence photons can be partially absorbed by the encapsulated material and will not show in the spectrum. The X-ray transmission image provides a complete picture.

Packaging must provide protection, minimize the loss of constituents and should have no physical or chemical interaction which could alter the quality or present a toxicity risk. With its high degree of versatility, the XGT-9000, HORIBA’s new X-ray microscope, is the perfect tool for the pharmaceutical industry as it can be easily applied within industrial settings, as well as R&D.

纳米毒理学需要对纳米材料进行物理化学表征，以研究组织培养物或模型生物体接触异生物的健康影响。 此类物质可以使用拉曼显微镜进行分析，这对于进行生理学、药理学和毒理学评估非常有用。与标准的暗场显微镜相比CytoViva 获得专利的增强暗场 (EDF) 照明非常适合检测复杂环境（如组织）中存在的非常小的外源性物质，然后用高光谱成像（HSI、CytoViva）来根据其光学特性区分组分特征。 将 EDF 和 HSI 添加到 HORIBA Scientific 的共聚焦拉曼显微镜中，可以在一个平台上进行从检测到区分再到化学鉴定的完整分析（无样移动样品）。

We have measured solutions of lysozyme under conditions known to effect its physical state in order to investigate the potential of Raman spectroscopy as a non-invasive and label-free tool to assess protein formulation stability. Results from this study identified specific Raman signature bands in this protein that can be used to identify individual amino acid residues that are reflect structural changes in proteins.

活性分子的多态性表征是制药业的重要信息之一，不仅是在原始粉末上，而且在最终形式上。拉曼光谱仍然是这种应用的合适的解决方案。在本文中，我们介绍了一个使用超低频模块通过拉曼光谱进行多态性表征的例子。

为了控制医药产品的配方，表征其活性成份是至关重要的，特别是在颗粒的形态和化学表征方面。在本应用说明中，我们分析了来自一个仿制药和一个创新药的两种配方，以比较其化合物的大小和形状，并根据LabSpec 6的ParticleFinderTM功能对这两种配方进行化学表征。重点对活性化合物进行了分析。

由于拉曼光谱技术与光学显微镜技术的结合，拉曼高光谱成像已经成为制药领域不可或缺的工具。本文将介绍我们实验室开发的一些拉曼高光谱成像技术的应用，以证明这项技术的重要性。

用于生物反应器的细胞培养基通常是水溶液，提供细胞最佳生长、产品产量和质量所需的基本营养与条件。培养基成分的细微变化都可能显著影响细胞生长速率和产量。因此，对细胞培养基的鉴定与分析对于保持一致性和优化性能至关重要。

本技术说明将动态荧光描述为一种可定量化非荧光物质的分析技术。该技术用于测定溶液中的硫胺素（维生素B1）。在硫胺素转化为荧光硫色素时监测荧光强度的变化，并建立荧光强度增加速率和硫胺素浓度之间的关系。该技术已经被证明具有良好的灵敏度和选择性。

监测培养基的条件对促进再生药物和蛋白质合成等过程中的细胞增殖非常重要。由于培养基介质组份复杂，且荧光成份多样，因此需要荧光激发发射三维矩阵(EEM)来同时全面展现发光信息。本篇报告主要通过测量 EEM 来监测细胞增殖过程中的细胞培养基组份的变化。

采用同步荧光激发-发射矩阵(EEMs)和紫外-可见吸收光谱技术研究胰岛素的稳定性和聚集特性。胰岛素是由胰腺分泌的蛋白质激素，是基础代谢过程中不可或缺的物质。市售胰岛素治疗药物主要分为两大类：速效胰岛素和长效胰岛素。某些速效胰岛素与长效胰岛素之间的差异，有时仅在于蛋白质序列中 1-3 个氨基酸残基的不同。

本应用说明重点展示了 Duetta 荧光分光光度计在极低浓度下测量转铁蛋白的高灵敏度。该仪器可同步进行荧光和吸光度测量，为蛋白质分析提供了关键优势。同时，我们将 Duetta 获得的荧光检测结果与专用低容量台式分光光度计的吸光度检测结果进行了对比分析。

二维（2D）荧光激发-发射矩阵（EEM）光谱技术已被运用超过 30 年，用以表征或“指纹识别”生物样本。历史上，数据采集过程缓慢且需大量校正。随着电荷耦合器件（CCD）技术的进步及数据校正方法的改进，二维荧光光谱技术重新引起了研究界的广泛兴趣。

腺相关病毒(AAV)作为递送细胞与基因疗法及疫苗的病毒载体正得到广泛应用。随着生产规模扩大以满足日益增长的需求，我们需要更快获取更多信息。

基于激光衍射的粒度分析仪为营养保健品测量带来了与该技术在制药行业广受欢迎的相同优势：分析速度快、精度极高、配备适用于各类应用的样品处理系统，且测量粒径范围广泛。我们不难发现，粒度表征对营养保健品行业至关重要，因为此类信息不仅影响研发工作，还关乎质量控制。

外泌体是直径 30-150 纳米的细胞外囊泡，广泛存在于原核和真核生物中，并分布于血液、尿液等多种体液中。其内部携带蛋白质、脂质、核酸等生物活性成分，可参与细胞间通讯，调控免疫应答、组织再生等生理过程，但也可能促进癌症转移和神经退行性疾病发展。由于外泌体成分反映母细胞状态，它在疾病诊断方面具有重要潜力。此外，外泌体可作为药物载体，实现靶向递送，尤其是其穿越血脑屏障的能力，为中枢神经系统疾病治疗提供了新途径。干细胞来源的外泌体还具有促进组织修复的功能。

测量的目的是通过拉曼和FT-IR显微光谱法确定未知成分及其在药片中的各自分散情况。

拉曼光谱是制药业中一个强大且广泛使用的分析工具，可以在几秒钟内得到辅料和活性药物成分（API），强大的拉曼光谱库使化学鉴定变得容易。

制药和晶体样品通常需要详细的表征和分析，以优化样品的稳定性、物理特性以及涉及到活性药物的功效。此外，严格的监管和生产程序要求对固体盐形式的候选药物进行精确的表征，以及环境条件可能产生的影响。不同条件下的水合作用和结构对这种全面的表征非常重要。

Full and detailed characterization of pharmaceutical formulations is required before release of new drugs. When exposed to warm and humid weather over time, ingredients may undergo change in their hydration level, thus affecting the properties and/or efficiency of the drug. Raman spectroscopy, combined to a temperature and humidity controller can mimic such harsh conditions and can be used to monitor the properties of the different ingre-dients and track their modifications induced by environmental changes.

通过拉曼光谱和光学显微镜的结合，拉曼高光谱成像已被证明是制药领域不可或缺的工具，特别是在研究药物产品中的活性物质和辅料的分布。

透射拉曼模式相较于传统背散射模式，为材料分析提供了额外灵活性，尤其适用于需要大体积样品平均信息的场景。透射方式测量解决了传统背散射耦合显微镜无法解决的问题。尽管不是新技术，但透射拉曼光谱（TRS）因高功率近红外激光器和专用配件的结合而备受关注。TRS 适用于扩散材料，如制药领域的片剂和胶囊，也适用于其他需要整个样品分析的扩散性和半透明材料。其在生物材料、食品和聚合物等领域均有应用实例，还可成功测量包装内的样品。

拉曼光谱有许多有用的特性，可以在分析药物配方时加以探索和利用：特定的指纹光谱；原位、非接触，最重要的是非破坏性分析；无定形和结晶相的区分；检测晶体的晶格振动；单颗粒表征；快速和强大的原材料分析；自动化和封闭式操作。

在过去的5-10年中，分子固体状态因其在药物生产、稳定性和活性方面的关键作用而受到制药业的重视。同时，在专利保护方面，结晶相的定义已与分子组成同等重要。简单的拉曼测量即可区分不同材料，如立体异构体、多晶形现象及伪多形性（由于水合作用）。拉曼仪器在医药产品鉴定方面的潜力正待开发。

A virus particle consists of several parts including the genetic material (DNA or RNA), a protein coat that protects these genes, and in some cases an envelope of lipids that surrounds the protein coat when they are outside a cell. The size of viruses ranges from a few tens to a few hundreds of nm, which is equal to 1/100 to 1/1000 of the cell (a few to a few tens of μm in size) of any other common living organism.

在食品质量控制、医药和化妆品生产等领域，污染微生物的鉴定是一个重要的公共安全问题。之前的研究表明，将拉曼光谱与化学计量学方法相结合可以鉴定块装样品以及单个细菌和酵母细胞，以便在物种和菌株水平上进行分类。

识别样本中微生物仍然是环境和医学研究中的一项重大挑战。由于许多细菌无法分离和培养，基于培养物的传统分析技术对细菌分析人员来说存在重大缺陷。 拉曼和显微镜在共聚焦拉曼显微镜仪器（如 LabRAM）中的组合允许在无需培养的条件下几分钟内成功分析离散的单个细菌细胞。

The complexity of viral particles remains one of the biggest hurdles in the development process. In this note, the upstream process of analyzing viral preparations is addressed, as well as the use of multi-laser nanoparticle tracking analysis (NTA) as a cost and time efficient method to measure size, count virus particles, and correlate to infectious titer.

Protein aggregation is an important concern when developing and manufacturing biotherapeutics since these subvisible aggregate particles have been associated with the adverse drug reactions. Protein aggregates may provoke adverse events through an unwanted immune response. And, regardless of mechanism of reaction, subvisible particle contamination has been a concern for manufacturers and regulators.

Size matters in vaccine delivery systems. Nanoparticles smaller than 200 nm generally present a greater immunogenic response than micro-particles larger than 1 micron. This rather simple statement is based on the common understanding that particles with sizes resembling the dimensions of viruses are treated like viruses by the body.

The study of protein aggregation encompasses a broad range of interactions and mechanisms. Many studies into this subject area investigate the aggregation of misfolded proteins, which is thought to be responsible for many degenerative diseases. Since aggregation typically leads to a physical change in protein size, particle size analysis has proven to be a useful experimental technique in this field.

The ViewSizer 3000 enables scientists to visualize and quantify the kinetics of protein aggregation in real-time for biologic therapeutics under a variety of stress conditions including agitation, temperature and the addition of contaminants. The case study featured here validates these capabilities for agitation and temperature stress conditions with the 100 mg/mL mAb A.

Protein scientists typically discuss “protein size” or molecular weight, as opposed to using the phrase “particle size”, but particle size analyzers are often used in their studies. There is also interest in the surface charge or valence of proteins, so zeta potential is another measurement used by protein chemists.

Zeta potential is a key physical parameter that describes surface charge on proteins. Although there has been interest in measuring the zeta potential of proteins for many years, the measurements were often difficult due to a variety of reasons including the “cooking” of proteins on the cell electrodes when using light scattering techniques.

Nanoparticles used for drug delivery is an important research field combining the life sciences with nanotechnology. While the strict definition of a nanoparticle is between 1 – 100 nm, we can extend the upper size range in the context of this application up to approximately 500 nm. Laser diffraction provides the advantage of being able to measure larger particles.

Considerable research has been conducted exploring the use of nanoparticles composed of biopolymers as a drug delivery vehicle. Much of the particle size analysis in this field has been done using dynamic light scattering (DLS). However, certain materials will feature larger particles that are outside the upper size range of DLS, but within the capability of laser diffraction.

The particle size distribution of active ingredients and excipients is an important physical characteristic of the materials used to create pharmaceutical products. The size, distribution and shape of the particles can affect bulk properties, product performance, processability, stability and appearance of the end product.

Nutraceuticals are the intersection of nutrition and pharmaceutical and is an umbrella term that can also include functional foods and dietary supplements. Nutraceutical researchers working to improve the bioavailability, biocompatibility, and stability of various formulations measure particle size, particle shape, and zeta potential.