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（由申请人提供）：对映异构体的分离（即，手性分离）在开发安全的手性药物和研究其它光学活性生物相关分子中具有重要意义。对于手性的药物化合物，通常一种对映体（右手或左手形式）是药物，而另一半会引起副作用，不同的效果，相似的效果或在有限的情况下，没有效果。该SBIR项目将支持基于表面多孔颗粒（SPP）的手性固定相（CSP）的开发。SPP是基于二氧化硅的色谱支持物，其具有固体、不可渗透的核心，与传统的全多孔颗粒（FPP）相比，这可以导致大大改进的柱填充材料。我们的初步研究结果证明了刷型手性选择剂键合到SPP的可行性（第一次）。经测定，当与类似的基于FPP的CSP相比时，可以获得SPP的多孔部分的类似手性选择剂表面覆盖率，从而产生等效的对映体选择性值。与具有类似手性选择剂的商业柱相比，基于SPP的CSP的柱效率大大提高，同时分析时间缩短50-75%。当调整移动的相条件以在商业FPP柱和新SPP手性柱上得到相似的保留时间时，分离度值几乎增加了一倍。此外，SPP填充柱可以在高流速下使用，而不会损失通常与现有技术手性柱相关的分离性能。正因为如此，我们已经证明了使用SPP为基础的CSP的超快速手性分离正在进行秒的时间尺度。该第二阶段SBIR提案的目的是开发许多独特的手性选择剂用于商业化，其将提供一系列稳定的、键合的、刷型SPP基CSP，其可用于LC/SFC的任何模式，并且可提供对映体分离的广泛选择性/高成功率，同时大大减少分析时间。具体而言，我们将开发这些CSP的生产方法（即，合成和包装方法），测试其重现性，建立原型柱供我们目标市场的专家评估，完善放大程序为生产做准备，并开始营销和与合作伙伴、分销商和未来投资者形成战略联盟。作为这项工作的结果，这项技术将为市场带来一种新的工具，可以生产更好、更便宜的药品，副作用更少，剂量更低。这些CSP将在制药、医药和合成有机化学中作为分离介质发挥重要作用。