ARLINGTON, TX, United States
ARLINGTON, TX, United States

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The present invention relates to a novel stationary phase support for liquid chromatographic chiral separations. The specific combination of the special underlying support material and certain classes of known chiral selectors according to the invention produces far superior chiral (enantiomeric) separations than those obtained on any conventionally known supports. These chiral (enantiomeric) separations are enhanced in terms of significantly higher efficiencies (theoretical plate numbers), higher resolutions (Rs), shorter retention times and either equivalent or slightly higher selectivities than those obtained on conventional supports.


The present invention relates to superficially porous particles (SPPs), also called core-shell, porous shell or fused core particles, which are state-of-the-art support materials used in the production of HPLC columns. Hydrolytically stable, highly selective superficially porous particle (SPP) hydrophilic interaction liquid chromatographic (HILIC) stationary phases having higher efficiencies and shorter retention times than analogous stationary phases on fully porous particles (FPP) is provided.


The present invention relates to a novel stationary phase support for liquid chromatographic chiral separations. The specific combination of the special underlying support material and certain classes of known chiral selectors according to the invention produces far superior chiral (enantiomeric) separations than those obtained on any conventionally known supports. These chiral (enantiomeric) separations are enhanced in terms of significantly higher efficiencies (theoretical plate numbers), higher resolutions (R_(s)), shorter retention times and either equivalent or slightly higher selectivities than those obtained on conventional supports.


The present invention relates to superficially porous particles (SPPs), also called core-shell, porous shell or fused core particles, which are state-of-the-art support materials used in the production of HPLC columns. Hydrolytically stable, highly selective superficially porous particle (SPP) hydrophilic interaction liquid chromatographic (HILIC) stationary phases having higher efficiencies and shorter retention times than analogous stationary phases on fully porous particles (FPP) is provided.


Padivitage N.L.T.,University of Texas at Arlington | Dodbiba E.,University of Texas at Arlington | Breitbach Z.S.,University of Texas at Arlington | Armstrong D.W.,University of Texas at Arlington | Armstrong D.W.,Azyp, Llc
Drug Testing and Analysis | Year: 2014

Recently a novel class of chiral stationary phases (CSPs) based on cyclofructan (CF) has been developed. Cyclofructans are cyclic oligosaccharides that possess a crown ether core and pendent fructofuranose moieties. Herein, we evaluate the applicability of these novel CSPs for the enantiomeric separation of chiral illicit drugs and controlled substances directly without any derivatization. A set of 20 racemic compounds were used to evaluate these columns including 8 primary amines, 5 secondary amines, and 7 tertiary amines. Of the new cyclofructan-based LARIHC columns, 14 enantiomeric separations were obtained including 7 baseline and 7 partial separations. The LARIHC CF6-P column proved to be the most useful in separating illicit drugs and controlled substances accounting for 11 of the 14 optimized separations. The polar organic mode containing small amounts of methanol in acetonitrile was the most useful solvent system for the LARIHC CF6-P CSP. Furthermore, the LARIHC CF7-DMP CSP proved to be valuable for the separation of the tested chiral drugs resulting in four of the optimized enantiomeric separations, whereas the CF6-RN did not yield any optimum separations. The broad selectivity of the LARIHC CF7-DMP CSP is evident as it separated primary, secondary and tertiary amine containing chiral drugs. The compounds that were partially or un-separated using the cyclofructan based columns were screened with a Cyclobond I 2000 RSP column. This CSP provided three baseline and six partial separations. © 2013 John Wiley & Sons, Ltd.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 139.87K | Year: 2011

DESCRIPTION (provided by applicant): The enantiomeric resolution of optical isomers is of great importance in the development of safe chiral pharmaceuticals and the study of chiral biological toxins and carcinogens. For pharmaceutical compounds that are chiral, usually one enantiomer (either the right or left-handed version) is the drug, while the other half causes side effects, different effects, similar effects or in limited cases, no effects. In the case of biological toxins, understanding the chiralityinvolved in their mechanism of action is necessary. This Small Business Innovation Research (SBIR) project will support the development of novel chiral selectors and chiral stationary phases based on the new cyclic oligosaccharide cyclofructan. Cyclofructans, or cycloinulooligosaccharides, are 2-(2-1)-linked cyclic fructofuranose oligomers. In their native forms, they show little enantioselectivity when used as chiral stationary phases. However, initial results indicate that certain derivatives of cyclofructan may make outstanding chiral selectors. This unique enantioselective chromatographic media is likely to be the greatest advancement in the resolution of enantiomers in the past 15 years. These chiral selectors will play a major role as separation mediain pharmaceutical, medicinal, and synthetic organic chemistry. The aim of Phase I of this SBIR is to see if we can develop this technology as broadly effective chiral stationary phases. Specifically, the proper derivatives, their degree of substitution, and the chromatographic support for these chiral selectors will be examined. Phase II of this project will then be used to develop this technology to commercialization level by providing scale up and preparative research and development. As a result of thisproposed 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. Also, we have better means to study their distribution and action in biological experiments and understand the biological actions of chiral toxins. PUBLIC HEALTH RELEVANCE: Pharmaceutical compounds that are chiral (from the Greek word for hand ) can exist as enantiomers (i.e., right and left-handed versions of the same basic compound). For medicines of this sort, usual one enantiomer (either the right or left-handed version) is the drug, while the other half causes side effects, different effects, similar effects or in limited cases, no effects. Since 1992 the Food and Drug Administration has had specific guidelines in place for the development and use of these types of drug products. In our proposed research we introduce a new class of chiral selectors called cyclofructans. We propose to develop synthetically altered cyclofructans that can be used to analyze, separate and purify most classes of chiral pharmaceutical compounds. Furthermore, these chiral selectors will prove useful in the enantiomeric separation of other biologically relevant chiral compounds (i.e. carcinogens). To show this is feasible, we will have to discover the optimal derivatized/bonded cyclofructans for the separation of a wide range of enantiomers. We believe the cyclofructans to be the most important class of chiral selector in at least the last 15 years. As a result of this proposed work, we will have better and less expensive pharmaceutical products that have fewer side effects and can be given in lower doses. Also we have better means to study stereo-selective effectsof chiral biological toxins.


Grant
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.92K | Year: 2011

Agrochemical sales is a vast world market which exceeded $119 billion in sales in 2009 and is expected to grown at a rate of 10.4% in the next 3 to 5 years. China and India are the world's largest users of agrochemicals. This has allowed Asia to dominate the market and account for 43% of sales. The US is the second largest revenue generator, bringing in approximately 20% of global agrochemical sales. Thus it is of great importance to continue to improve the technology used to develop novel US based agrochemicals in order to remain a competitive entity in this market. Furthermore, the production of novel herbicides and pesticides has lead to an increase in the number of chiral agrochemicals. Hence it is becoming more essential that the means to produce enantiomerically pure agrochemicals is improved and expanded. The most important tool that will be used in the development of single-enantiomer agrochemicals are chiral selectors or chiral stationary phases (CSP), which are employed during enantioselective separation processes (i.e. high performance liquid chromatography (HPLC), super-critical fluid chromatography (SFC), and preparative chromatography). Currently, there are no CSPs that can separate all chiral agrochemicals. For this reason, it is critical that novel CSPs are developed as to further aid in the production of more effective and safer novel pesticides and herbicides. The proposed research will result in the production of a novel CSP that can be used to help enantiomerically purify agrochemicals. This purification will allow for safer and more effective herbicides and pesticides. In the public's interest, this research can be applied to nearly all USDA strategic goals. Being able to produce crops more effectively through the use of highly purified chiral agrochemicals will: allow American agriculture to remain internationally strong; allow rural framers to be more productive and successful; afford enhanced protection for crops and further secure our ability to continually meet the hunger needs of Americans; and improve the nation's health and protect our resources through the 50% reduction in environmental contaminants that occurs when racemic chiral agrochemicals are used.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 486.10K | Year: 2016

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 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 secondsandapos 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 PUBLIC HEALTH RELEVANCE Pharmaceutical compounds that are chiral from the Greek word for andquot handandquot can exist as enantiomers i e right and left handed versions of the same basic compound and for medicines of this sort usually one enantiomer either the right or left handed version is the drug while the other half causes side effects different effects similar effects r in limited cases no effects In our proposed research we introduce a new technology for the analysis and purification of chiral drugs which utilizes specialized packing materials called superficially porous particle based chiral stationary phases which in our feasibility studies proved to offer the ability to reduce chiral drug analysis times from tens of minutes to tens of seconds by greatly increasing the efficiency of the analysis and improving the ability to rapidly separate and purify most classes of chiral pharmaceutical compounds as well as other biologically relevant chiral molecules As a result of this proposed work Americans will have better and less expensive pharmaceutical products that have fewer side effects and can be given in lower doses and scientists will have better means to study stereo selective effects of chiral biological molecules


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 149.80K | Year: 2014

DESCRIPTION (provided by applicant): The effective separation and analysis of pharmaceutical compounds and their metabolites is essential to researchers that develop new, more effective, safer, and economical medicines. Novel types of biologically deriveddrug compounds (biologics) are becoming more important and prevalent as they match and sometimes exceed the importance of traditional small synthetic molecules. However, long-established high performance liquid chromatographic (HPLC) techniques often do not provide a means to effectively separate these biologics, which are typically highly polar molecules. Recently, hydrophilic interaction liquid chromatography (HILIC) has emerged as the analytical technique of choice to analyze highly polar drugs. HILIC isperhaps the fastest growing HPLC technique, but the commercially available stationary phases may not always be able to perform all the desired/needed separations. The aim of this Phase I Small Business Innovation Research (SBIR) project is to show fe


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 980.85K | Year: 2012

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 chiral biological toxins and carcinogens. For pharmaceutical compounds that are chiral, usually one enantiomer (either the right or left-handed version) is the drug, while the other half causes side effects, different effects, similar effects or in limited cases, no effects. In the cas of biological toxins, understanding the chirality involved in their mechanism of action is necessary. This Small Business Innovation Research (SBIR) project will support the development of novel chiral selectors and chiral stationary phases based on the new cyclic oligosaccharide cyclofructan. Cyclofructans, or cycloinulooligosaccharides, are -(2-1)-linked cyclic fructofuranose oligomers. In their native forms, they show little enantioselectivity when used as chiral stationary phases. However, Phase I results indicate that certain derivatives ofcyclofructan make outstanding chiral selectors. This unique enantioselective chromatographic media is likely to be the greatest advancement in the resolution of enantiomers in the past 15 years. These chiral selectors will play a major role as separation media in pharmaceutical, medicinal, and synthetic organic chemistry. The aim of the Phase II proposal of this SBIR is to further develop these broadly effective chiral stationary phases and to bring them to the commercialization level. Specifically, we willdevelop the production means for these chiral stationary phases (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 this 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. Also, we have better means to study their distribution and action in biological experiments and understand the biological actions of chiral toxins. PUBLIC HEALTHRELEVANCE: Pharmaceutical compounds that are chiral (from the Greek word for hand ) can exist as enantiomers (i.e., right and left-handed versions of the same basic compound). For medicines of this sort, usually one enantiomer (either the right or left-handed version) is the drug, while the other half causes side effects, different effects, similar effects r in limited cases, no effects. Since 1992 the Food and Drug Administration (FDA) has had specific guidelines in place for the development and use ofthese types of drug products. In our proposed research we introduce a new class of chiral selectors called cyclofructans. During our Phase I research, we proved the feasibility of synthetically altering cyclofructans so they can be used to analyze, separate and purify most classes of chiral pharmaceutical compounds. Furthermore, these chiral selectors will prove useful in the enantiomeric separation of other biologically relevant chiral compounds. We believe that cyclofructans are the most important class of chiral selectors to be discovered in at least the last 15 years. As a result of this proposed work, Americans will have better and less expensive pharmaceutical products that have fewer side effects and can be given in lower doses. Also we have better means to study stereoselective effects of chiral biological molecules including toxins.

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