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: 10483473
• 负责人: Balaji Sitharaman
• 金额: $ 51.81万
• 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/10483473
• 关键词: Advanced Development; Affect; Animals; Aromatic Compounds; Biological Assay; Caliber; Carbon; Carbon Nanotubes; Chromatography; Deposition; Detection; Development; Disease; 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 Products; Outcome; Performance; Phase; Plant Extracts; Plants; Powder dose form; Preparation; Procedures; Process; Reproducibility; Sampling; Silicon Dioxide; Small Business Innovation Research Grant; Solid; Source; System; Tannic Acid; Techniques; Technology; Temperature; Testing; commercialization; cost; double walled carbon nanotube; drug candidate; drug discovery; falls; graphene; improved; innovation; insight; instrumentation; nanofabrication; nanomaterials; next generation; pi bond; 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 天然产品仍然是吸毒发现的丰富来源。但是，对于 针对分子靶标的高吞吐量生物测定筛选是生物活性化合物混合物的分离 没有干扰滋扰化合物。植物中完善的无处不在的滋扰化合物 提取物是单宁 - 多酚植物代谢产物。固相提取（SPE）过程现在正在增加 识别作为快速分馏粗植物提取物的方法，并努力消除滋扰 在将它们引入更昂贵的气体或 液相色谱仪器。我们的客户发现采访发现 自然产物提取期间去除滋扰化合物的当前反向相材料 不适合单使用不适合单使用，pH（基本pH下降解）和温度（t>降解> 60°C）限制，以及在去除诸如单宁之类的滋扰化合物中的次优性能。这些 技术问题影响（增加）生产产品并提高利润率的运营成本。 SBIR II期提案的总体目标是最终确定创新的固相提取单元 结合了使用使用的全碳球形微粒（直径为40 µm），合成了使用 多壁碳纳米管（MWCNT）作为起始材料。该材料将在施加的电压下 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。目标1。 证明全碳微粒合成和固相提取底物是可扩展的。目的 2。在缩放的微粒和底物批次上建立一致的性能，并证明 （a）改善单宁的保留率，（b）通过电喷雾质谱法快速检测单宁蛋白， （c）重复使用墨盒。 预期结果包括1）设置和条件的最终确定，这将使大规模大规模 全碳固相提取系统的制造。 2）识别关键合成过程 影响单宁提取性能可重复性的参数（CPP），必须监控，并且必须受到监控和 受控以确保该过程产生所需的质量而无需批处理变异性。 3）最终确定 科学的声音和适当的测试方法，有时可以有资格/验证以释放批处理 测试。第二阶段活动的科学结果将有助于该产品的商业发布 以及启用其去除其他滋扰化合物的应用。完成后， Nanopak-C将吸引寻求下一代性能功能的客户 在天然产物提取过程中除去滋扰化合物的当前最新作品的能力 将活性药物从天然产物的纯化提取物中提前分离。