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）：对映体的分离（即手性分离）对于安全手性药物的开发和其他光学活性生物学相关分子的研究非常重要。对于手性药物化合物，通常是一种对映体（右手或左手版本）是药物，而另一半会产生副作用、不同的效果、类似的效果或在有限的情况下，没有效果。该 SBIR 项目将支持开发。基于表面多孔颗粒 (SPP) 的手性固定相 (CSP) 是基于二氧化硅的色谱载体，具有固体、不渗透的核心，与传统的全多孔颗粒 (FPP) 相比，可以大大改进柱填充材料。证明了将刷型手性选择器键合到 SPP 的可行性。确定了当 SPP 的多孔部分可以获得类似的手性选择器表面覆盖度时。与类似的基于 FPP 的 CSP 相比，与具有类似手性选择器的商业色谱柱相比，基于 SPP 的 CSP 的柱效大大提高，而当调整流动相条件时，分析时间缩短了 50-75%。为了在商业 FPP 色谱柱和新型 SPP 手性色谱柱上提供相似的保留时间，分辨率值几乎翻倍。此外，SPP 填充柱可以在高流速下使用，而不会损失通常相关的分离性能。因此，我们已经演示了使用基于 SPP 的 CSP 在秒级时间范围内进行超快速手性分离。第二阶段 SBIR 提案的目的是开发。一系列用于商业化的独特手性选择器，将提供一系列稳定、键合、刷式 SPP 的 CSP，可用于任何 LC/SFC 模式，并可为对映体提供广泛的选择性/高成功率具体来说，我们将开发这些 CSP 的生产方法（即合成和装填方法），测试其再现性，构建原型柱以供目标市场的专家评估，扩大精炼程序以准备生产，并开始营销和推广。与合作伙伴、分销商和未来投资者形成战略联盟，这项技术将为市场带来一种新工具，可以生产更好、更便宜、副作用更少的药品。这些 CSP 将在制药、医学和有机合成化学中作为分离介质发挥重要作用。