Electrochemically-Controlled Rapid Chromatographic Separation of Nuisance Compounds from Natural Product Extracts

电化学控制快速色谱分离天然产物提取物中的有害化合物

• 批准号: 10706533
• 负责人: Balaji Sitharaman
• 金额: $ 97.99万
• 依托单位: MILLENNIAL MATERIALS AND DEVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10706533
• 关键词: Advanced Development; Affect; Animals; Aromatic Compounds; Biological Assay; Carbon; Carbon Nanotubes; Chromatography; Deposition; Detection; Development; Diameter; Disease; Electric Conductivity; Electrospray Ionization; Ensure; Excision; Foundations; Fractionation; Gas Chromatography; High Pressure Liquid Chromatography; Hydrophobicity; Interview; Laboratories; Lead; Left; Legal patent; Liquid Chromatography; Mass Spectrum Analysis; Methods; Microspheres; Modernization; Molecular Target; Monitor; Natural Extract; Natural Products; Outcome; Performance; Phase; Plant Extracts; Powder dose form; Preparation; Procedures; Process; Qualifying; Reproducibility; Sampling; Silicon Dioxide; Small Business Innovation Research Grant; Solid; Source; System; Tannic Acid; Techniques; Technology; Temperature; Testing; commercial launch; commercialization; cost; double walled carbon nanotube; drug candidate; drug discovery; falls; graphene; improved; innovation; insight; instrumentation; large scale production; manufacture; manufacturing technology; meter; nanofabrication; nanomaterials; next generation; particle; pi bond; plant metabolites; prototype; rapid detection; rapid technique; scale up; screening; sound; voltage

Abstract Natural products remain a rich source of compounds for drug discovery. However, a significant challenge for high throughput bioassay screening against molecular targets is the isolation of bioactive compound mixture free from interfering nuisance compounds. The well-established ubiquitous nuisance compounds in plant extracts are Tannins - polyphenolic plant metabolites. The solid-phase extraction (SPE) process is now gaining recognition as a method for rapid fractionation of crude plant extracts and employed to remove nuisance compounds as well as purify and concentrate analytes before introducing them into more expensive gas- or liquid- chromatography instrumentation. Our customer discovery interviews found that the challenges with current reverse phase materials in the removal of nuisance compounds during natural product extraction include unsuitable for more than single-use, pH (degrades at basic pH) and temperature (degrades at T > 60°C) restrictions, and suboptimal performance in the removal of nuisance compounds such as tannins. These technical issues affected (increased) the operational costs to manufacture the product and decreased margins. This SBIR Phase II proposal’s overall objective is to finalize an innovative solid phase extraction unit that incorporates electrically-conducting all-carbon spherical microparticles (40 µM diameter), synthesized using multi-walled carbon nanotubes (MWCNTs) as starting material. This material will, under an applied voltage, facilitate selective separation and detection of tannins. During Phase II, two aims will be pursued. Aim 1. Demonstrate that the all-carbon microbead synthesis and solid-phase extraction substrates are scalable. Aim 2. Establish consistent performance across the scaled-up microbead and substrate batches, and demonstrate (a) improved retention of tannins, (b) rapid detection of trapped tannins by electrospray mass spectrometry, and (c) reuse of the cartridge. Expected outcomes include 1) Finalization of the setup and conditions that will enable the large scale manufacturing of all-carbon solid-phase extraction system. 2) Identification of the critical synthesis process parameters (CPP) that affects tannin extraction performance reproducibility and has to be monitored and controlled to ensure the process produces the desired quality without batch variability. 3) Finalization of scientifically sound and appropriate test methods that can eventually be qualified/validated for batch release testing. The scientific outcomes from the Phase II activities will facilitate the commercial launch of this product as well as enable its application for the removal of other nuisance compounds. Upon complete development, NanoPak-C will attract customers seeking next-generation performance capabilities that fall outside the capabilities of current state-of-art for the removal of nuisance compounds during natural product extraction and advance separation of active drug candidates from the purified extracts of natural products.

抽象的 天然产物仍然是药物发现的丰富化合物来源，但这对药物开发来说是一个重大挑战。 针对分子靶标的高通量生物测定筛选是生物活性化合物混合物的分离 不含植物中普遍存在的干扰化合物。 提取物是单宁 - 多酚植物代谢物 固相萃取 (SPE) 工艺现在正在取得进展。 被认为是一种快速分馏粗植物提取物的方法，并用于消除干扰 化合物以及纯化和浓缩分析物，然后将其引入更昂贵的气体或 我们的客户探索访谈发现，液相色谱仪器面临的挑战。 目前的反相材料在天然产物提取过程中去除有害化合物 包括不适合多次使用、pH（在碱性 pH 下降解）和温度（在 T > 时降解） 60°C）限制，并且在去除单宁等有害化合物方面表现不佳。 技术问题影响（增加）了产品制造的运营成本并降低了利润。 该 SBIR 第二阶段提案的总体目标是最终确定一种创新的固相萃取装置，该装置 包含导电全碳球形微粒（直径 40 µM），使用合成 多壁碳纳米管（MWCNT）作为起始材料，在施加电压下，该材料将 促进单宁的选择性分离和检测 在第二阶段，将实现两个目标 1。 证明全碳微珠合成和固相萃取底物具有可扩展性。 2. 在放大的微珠和基质批次中建立一致的性能，并证明 (a) 改善单宁的保留， (b) 通过电喷雾质谱法快速检测捕获的单宁， (c) 滤筒的重复使用。 预期成果包括 1) 最终确定能够实现大规模生产的设置和条件 全碳固相萃取系统的制造2）关键合成工艺的确定。 影响单宁提取性能再现性的参数（CPP）必须进行监测和 进行控制，以确保过程产生所需的质量，且没有批次差异。 3) 最终确定。 科学合理且适当的测试方法最终可以通过批量放行的资格/验证 第二阶段活动的科学成果将促进该产品的商业推出。 并使其能够用于去除其他有害化合物。 完成开发后， NanoPak-C 将吸引寻求超出范围的下一代性能能力的客户 目前最先进的技术在天然产物提取过程中去除有害化合物的能力 从天然产物的纯化提取物中提前分离活性候选药物。