Superficially Porous Silica Based Chiral Stationary Phases for High Efficiency and High Speed Pharmaceutical Analysis and Purification

用于高效、高速药物分析和纯化的表面多孔二氧化硅手性固定相

• 批准号: 9222777
• 负责人: Jauh Tzuoh Lee
• 金额: $ 48.61万
• 依托单位: AZYP, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9222777
• 关键词: Adverse effects; American; Area; Biological; Chromatography; Column Chromatography; Complex; Cyclodextrins; Development; Dose; Ensure; Evaluation; Feasibility Studies; Funding; Future; Greek; Growth; Hand; High Pressure Liquid Chromatography; Left; Marketing; Medicine; Methods; Neck; North America; Optics; Organic Chemistry; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Play; Preclinical Drug Evaluation; Preparation; Procedures; Process; Production; Reproducibility; Research; Resolution; Role; Sales; Scientist; Secure; Silicon Dioxide; Small Business Innovation Research Grant; Solid; Speed; Supercritical Fluid Chromatography; Surface; Technology; Teicoplanin; Testing; Time; Vancomycin; Work; base; chiral molecule; commercialization; enantiomer; improved; innovative technologies; molecular recognition; new technology; novel; particle; prototype; public health relevance; scale up; screening; stability testing; success; tool

 DESCRIPTION (provided by applicant): The separation of enantiomers (i.e., chiral separations) is of great importance in the development of safe chiral pharmaceuticals and the study of other optically active biologically relevant molecules. For pharmaceutical compounds that are chiral, usually one enantiomer (either the right or left-handed version) is the drug, whil the other half causes side effects, different effects, similar effects or in limited cases, no effets. This SBIR project will support the development of superficially porous particle (SPP) based chiral stationary phases (CSPs). SPPs are silica based chromatographic supports that possess a solid, impermeable core which can result in greatly improved column packing materials compared to traditional fully porous particles (FPPs). Our preliminary results demonstrated feasibility (for the first time) of bonding brush-type chiral selectors to SPPs. It was determined that similar chiral selector surface coverage of the porous portion of the SPPs could be obtained when compared to analogous FPP based CSPs, resulting in equivalent enantiomeric selectivity values. Column efficiencies of the SPP based CSPs were greatly improved compared to commercial columns with analogous chiral selectors, while the analysis times were 50-75% shorter. When mobile phase conditions were adjusted to give similar retention times on a commercial FPP column and a new SPP chiral column, resolution values nearly doubled. Further, SPP packed columns can be used at high flow rates without the loss in separation performance typically associated with the current state of the art chiral columns. Because of this, we have demonstrated the use of SPP based CSPs for ultra-fast chiral separations being performed in the seconds' time-scale. The aim of this Phase II SBIR proposal is to develop a number of unique chiral selectors for commercialization which will offer an array of stable, bonded, brush-type SPP based CSPs that can be used in any mode of LC/SFC and can offer broad selectivity/high success rates for enantiomeric separations with greatly reduced analysis times. Specifically, we will develop the production means for these CSPs (i.e., synthesis and packing methods), test their reproducibility, build prototype columns for evaluation by experts in our target market, refine scale-up procedures to prepare for manufacturing, and begin marketing and forming strategic alliances with partners, distributors, and future investors. As a result of tis proposed work, this technology will bring to market a new tool that will allow for the production of better and less expensive pharmaceutical products that have fewer side effects and can be given in lower doses. These CSPs will play a major role as separation media in pharmaceutical, medicinal, and synthetic organic chemistry.

 描述（由适用提供）：对映异构体的分离（即手性分离）在开发安全性手性药物以及对其他光学活性生物学相关分子的研究中至关重要。对于手性的药物化合物，通常一种对映异构体（右手或左手版本）是药物，而另一半则会引起副作用，不同的效果，相似的效果或在有限的情况下，没有expets。该SBIR项目将支持基于超多孔粒子（SPP）的手性固定相（CSP）的发展。 SPP是基于二氧化硅的色谱支持，具有固体，不可渗透的核心，与传统上完全多孔颗粒（FPP）相比，可以大大改善柱状堆积材料。我们的初步结果表明（这是首次）将刷型手性选择器与SPPS结合的可行性。可以确定，与基于类似FPP的CSP相比，可以获得SPP的多孔部分的类似手性选择器表面覆盖率，从而导致等效的对映体选择性值。与具有类似手性选择器的商业柱相比，基于SPP的CSP的柱效率大大提高，而分析时间短50-75％。当调整流动相条件以在商业FPP色谱柱和新的SPP手性柱上给出相似的保留时间时，分辨率值几乎翻了一番。此外，SPP填充的柱可在高流量下使用，而不会与直率的手性柱的当前状态相关的分离性能损失。因此，我们已经证明了基于SPP的CSP在秒的时间尺度内进行超快速性手性分离。该II阶段SBIR提案的目的是开发许多用于商业化的独特手性选择器，这些选择器将提供一系列稳定的，粘合的，刷子型SPP的CSP，可在任何LC/SFC的任何方式中使用，并可以为映体分离提供广泛的选择性/高成功率，并具有很大的降低分析时间。具体来说，我们将开发这些CSP（即合成和包装方法）的生产手段，测试其可重复性，构建原型列，以评估我们的目标市场的专家，完善制造计划，以准备制造制造业，并开始与合作伙伴，分销商，分销商，未来投资者和未来的投资者进行营销和建立战略联盟。由于提出的工作，这项技术将为销售一种新工具，该工具将允许生产更便宜，更便宜的药品，这些产品具有更少的副作用，并且可以以较低的剂量给出。这些CSP将在药物，医学和合成有机化学中作为分离培养基起主要作用。