Automated technology for purification of active ingredients in natural products

天然产物中活性成分纯化的自动化技术

• 批准号: 8016664
• 负责人: Guido F Pauli
• 金额: $ 38.1万
• 依托单位: WRIGHTWOOD TECHNOLOGIES INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8016664
• 关键词: Area; Automation; Biochemical; Biological Factors; Botanicals; Characteristics; Chemicals; Complex; Consumption; Data; Data Analyses; Data Storage and Retrieval; Development; Disease; Environment; Feedback; Future; Goals; Information Systems; Knowledge; Liquid substance; Location; Measurement; Measures; Minor; Modeling; Monitor; Nature; Partition Coefficient; Performance; Phase; Positioning Attribute; Process; Property; Recovery; Research; Research Personnel; Research Proposals; Running; Sampling; Small Business Innovation Research Grant; Solid; Solvents; System; Techniques; Technology; Time; Training; Tuberculosis; United States National Institutes of Health; base; chemical property; combat; countercurrent chromatography; data acquisition; dietary supplements; empowered; experience; fight against; human disease; instrument; journal article; meter; multidisciplinary; prevent; prototype; public health relevance; sensor; success; tool; virtual

DESCRIPTION (provided by applicant): The analysis of complex natural mixtures presents a significant scientific challenge in biomedical studies involving natural products and other complex biogenic samples, particularly when the need for isolation of minor constituents arises. Countercurrent chromatography (CCC) offers high loading capacity, complete sample recovery, and high purity fractions. It makes use of a gentle liquid stationary phase that prevents degradation of labile samples, and is already a valuable tool in natural products research. CCC separations consume relatively little solvent and don't require the use of expensive solid supports, making them highly economical, both environmentally and fiscally. The frugal use of consumables makes CCC much more "green" than other competing technologies. Determination of partition coefficients (K-values) is a unique analytical capability offered by CCC. However, accurate measurement of analyte partition coefficients with modern CCC instruments requires that sample loading be constrained far below system capacity. With current technology, the unique practical advantages of CCC are essentially lost when the conditions are optimized to determine K- values. In addition, successful use of CCC currently requires specialized training and considerable operator time. Automation, as it has for many other technologies, could effectively mitigate both the academic burden of assimilating decades of key information spread over hundreds of journal articles, and the practical burden of operating a complex multi-component system. Challenges imposed by the dynamic nature of the liquid CCC column had prevented the development of automated CCC until the SBC achieved a breakthrough proof of concept during Phase I of this SBIR project. The long-term objective of this project, and the ultimately marketable product, will be a fully functional automated CCC controller that will provide the separation power of CCC to minimally trained users, as well as enhance current capabilities and provide new functionality to experienced users. Automated CCC will provide a significant contribution to the goals of the National Institutes of Health (NIH), empowering biomedical researchers in their quest to analyze complex bioactive samples and alleviate human disease. The success of this project will be demonstrated by its application to the purification and study of bioactive natural products present in commonly consumed botanical products, one of which has shown promise in the fight against tuberculosis. PUBLIC HEALTH RELEVANCE: The analysis of highly complex chemical mixtures presents a significant scientific challenge, particularly in biomedical studies involving natural products and other complex biogenic samples. Countercurrent chromatography (CCC) is a technique, originally developed at NIH, which is able to solve many challenges in this area. This SBIR research proposal provides the key piece of technology required to bring the immense potential of CCC's analytical capabilities to realization, empowering biomedical researchers with a much-needed new tool in the arsenal to combat disease through biochemical discovery.

描述（由申请人提供）：复杂自然混合物的分析在涉及天然产物和其他复杂生物样品的生物医学研究中提出了重大的科学挑战，尤其是在需要隔离次要成分时。逆流色谱法（CCC）具有高负载能力，完整的样品回收和高纯度分数。它利用了防止不稳定样品降解的温和液体固定相，并且已经是天然产品研究中的宝贵工具。 CCC分离消耗的溶剂相对较少，并且不需要使用昂贵的固体支撑，这使得它们在环境和财政上都非常经济。节俭使用消耗品使CCC比其他竞争技术更“绿色”。分区系数的确定（K值）是CCC提供的独特分析能力。但是，使用现代CCC仪器对分析物分区系数进行准确测量要求将样品加载远低于系统容量。借助当前技术，当对条件进行优化以确定K值时，CCC的独特实用优势本质上会丢失。此外，当前成功使用CCC需要专门的培训和大量的操作员时间。与许多其他技术一样，自动化可以有效地减轻数十年的关键信息的学术负担，分布在数百篇期刊文章中，以及操作复杂的多组分系统的实际负担。液体CCC色谱柱的动态性质所面临的挑战阻止了自动化CCC的发展，直到SBC在该SBIR项目的I期中获得了突破性的概念证明。该项目的长期目标以及最终可销售的产品将是功能齐全的自动化CCC控制器，它将为CCC的分离能力提供给最小培训的用户，并增强当前功能并为有经验的用户提供新的功能。自动化的CCC将为美国国立卫生研究院（NIH）的目标做出重大贡献，赋予生物医学研究人员的能力，以寻求分析复杂的生物活性样本并减轻人类疾病。该项目的成功将通过其应用于普遍消耗的植物产品中存在的生物活性天然产品的纯化和研究，其中一种在与结核病作斗争中表现出了希望。 公共卫生相关性：对高度复杂化学混合物的分析提出了重大的科学挑战，尤其是在涉及天然产物和其他复杂生物样品的生物医学研究中。逆流色谱法（CCC）是一种最初在NIH开发的技术，该技术能够解决该领域的许多挑战。这项SBIR研究建议提供了将CCC分析能力的巨大潜力带入实现所需的关键技术，从而通过生物化学发现赋予了急需的新工具，从而使生物医学研究人员具有急需的新工具来对抗疾病。

项目成果

Real-Time Volumetric Phase Monitoring: Advancing Chemical Analysis by Countercurrent Separation.

• DOI: 10.1021/acs.analchem.5b01613
• 发表时间: 2015-07-21
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Pauli GF;Pro SM;Chadwick LR;Burdick T;Pro L;Friedl W;Novak N;Maltby J;Qiu F;Friesen JB
• 通讯作者: Friesen JB