SBIR-STTR Award

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 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-(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 media in 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 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 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 effects of chiral biological toxins.

Thesaurus Terms:
Accounting;Adverse Effects;Amines;Area;Biological;Cancer Causing Agents;Carcinogens;Chromatography;Chromatography / Separation Science;Chromatography, High Performance Liquid;Chromatography, High Pressure Liquid;Chromatography, High Speed Liquid;Development;Development And Research;Dose;Drugs;Fda;Food And Drug Administration;Food And Drug Administration (U.S.);Generalized Growth;Greek;Growth;Guidelines;Hplc;Hand;High Pressure Liquid Chromatography;Isomerism;Lc/Ms;Left;Link;Liquid Substance;Marketing;Medication;Medicine;Modification;North America;Oligosaccharides;Oncogens;Optics;Organic Chemistry;Pharmaceutic Preparations;Pharmaceutical Agent;Pharmaceutical Preparations;Pharmaceuticals;Pharmacologic Substance;Pharmacological Substance;Phase;Play;Preparation;Process;Production;R &D;R&D;R01 Mechanism;R01 Program;Rpg;Research;Research Grants;Research Project Grants;Research Projects;Research Projects, R-Series;Resolution;Role;Sbir;Sbirs (R43/44);Sales;Science Of Medicine;Small Business Innovation Research;Small Business Innovation Research Grant;Sorting - Cell Movement;Technology;Testing;Tissue Growth;Toxin;Treatment Side Effects;Usfda;United States Food And Drug Administration;Work;Base;Commercialization;Drug /Agent;Drug/Agent;Enantiomer;Experiment;Experimental Research;Experimental Study;Fluid;High Performance Liquid Chromatography;Improved;Isomer;Liquid;Liquid Chromatography Mass Spectrometry;Molecular Recognition;Novel;Ontogeny;Research And Development;Research Study;Scale Up;Side Effect;Social Role;Sorting;Therapy Adverse Effect;Tool;Treatment Adverse Effect

Clinical science and its translation into preventive and clinical patient care are the primary means by which the nation's health care goals are fulfilled. NIH's broad mission to improve health outcomes for all people can only be achieved if scientific advances are transformed into improvements in public health. As emphasized throughout the NIH Roadmap, there is a critical need to build our nation's research capacity for clinical and translational research so that findings can be more quickly and effectively translated into clinica practice. This Phase II SBIR project will continue the research and development of Research Implementation and Management System (RIMS), the first integrated system of online research tools specifically designed to meet the needs of clinical and translational scientists in the socia and behavioral fields. Through efficient, cost- effective, and tailored research implementation and management tools, RIMS will harness the Internet's power to effectively increase research capacity. RIMS will integrate and streamline all needed research activities from recruitment and retention to human participant protections to data collection and database management. RIMS will be broadly applicable, providing customizable tools that can be easily integrated into a research protocol. Further, RIMS' online tools are built on robust, HIPAA-compliant data security standards. No other product provides a comprehensive suite of integrated research implementation and management tools tailored to the needs of social/behavioral researchers. Phase I feasibility test results with researchers provide strong support for continued development and testing of RIMS. During Phase II, we will build on Phase I feedback to finalize the fully functioning web-based product and conduct a field test examining the degree to which RIMS enhances the quality, efficiency, and cost-effectiveness of clinical and translational research. This Phase II project will accomplish three specific aims: 1) Full product development and usability testing with clinical and translational researchers in the social and behavioral sciences (PIs, Project Coordinators, & Research Staff; n=20 per group); 2) Field testing in collaboration with 12 research teams to examine the impact of RIMS over a 6-month period in cost-effectiveness, time efficiency, recruitment and retention, data quality, and satisfaction; and 3) finalizing the product based on test results and user evaluations. Over the course of 3-C ISD's work with research scientists, it has become clear there is a large unmet need and demand for web-based research management tools, particularly in social and behavioral fields (see letters of support). By making such technologies affordable and broadly applicable, RIMS has the potential to significantly advance the research capacity of clinical and translational research through high quality, time-efficient, and cost-effective research management and implementation tools. As a result, our nation's ability to transform research findings into improved health outcomes can be strengthened and accelerated.

Public Health Relevance:
NIH's mission to improve health outcomes for all people emphasizes the need to accelerate and strengthen clinical and translational research. Technology can play a vital role in achieving this goal through web-based tools for researchers that allow them to conduct, disseminate, and translate their research more efficiently and with higher quality. Currently, comprehensive web-based tools are rarely used in the service of clinical or translational research in the social and behavioral sciences. Social and behavioral research plays a critical role in advancing the understanding and prevention of public health problems, both at the individual level (e.g., drug and alcohol abuse) and at the systems level (e.g., health economics, delivery systems). The treatment and prevention of diabetes, obesity, drug abuse, violence, and myriad other public health concerns depend on good research that is conducted cost-effectively and translated efficiently. The proposed Research Implementation Management System (RIMS) will offer a suite of online research tools to streamline the various activities needed to conduct clinical and translational research in the social and behavioral sciences, including recruitment, retention, human participant protections, measure construction, data collection, and database management. This product will be developed and tested in response to the needs of clinical and translational researchers across a broad array of social and behavioral fields. The underlying web-based technology infrastructure of RIMS will be broadly applicable, providing customizable tools that can be easily integrated into a research protocol. RIMS will bridge geographic barriers by giving researchers with fewer institutional supports for research equal access to affordable, flexible technology. In effect, this SBIR will be able to support the research of scientists across multiple NIH Institutes, with particular relevanc for the National Institute for Mental Health (NIMH), National Institute on Drug Abuse (NIDA), National Institute on Aging (NIA), and the National Institute of Child Health and Human Development (NICHD). Bringing the RIMS product to market would broadly support NIH's mission to improve public health outcomes through strengthening capacity of clinical and translational science.

Public Health Relevance Statement:
NIH's mission to improve health outcomes for all people emphasizes the need to accelerate and strengthen clinical and translational research. Technology can play a vital role in achieving this goal through web-based tools for researchers that allow them to conduct, disseminate, and translate their research more efficiently and with higher quality. Currently, comprehensive web-based tools are rarely used in the service of clinical or translational research in the social and behavioral sciences. Social and behavioral research plays a critical role in advancing the understanding and prevention of public health problems, both at the individual level (e.g., drug and alcohol abuse) and at the systems level (e.g., health economics, delivery systems). The treatment and prevention of diabetes, obesity, drug abuse, violence, and myriad other public health concerns depend on good research that is conducted cost-effectively and translated efficiently. The proposed Research Implementation Management System (RIMS) will offer a suite of online research tools to streamline the various activities needed to conduct clinical and translational research in the social and behavioral sciences, including recruitment, retention, human participant protections, measure construction, data collection, and database management. This product will be developed and tested in response to the needs of clinical and translational researchers across a broad array of social and behavioral fields. The underlying web-based technology infrastructure of RIMS will be broadly applicable, providing customizable tools that can be easily integrated into a research protocol. RIMS will bridge geographic barriers by giving researchers with fewer institutional supports for research equal access to affordable, flexible technology. In effect, this SBIR will be able to support the research of scientists across multiple NIH Institutes, with particular relevanc for the National Institute for Mental Health (NIMH), National Institute on Drug Abuse (NIDA), National Institute on Aging (NIA), and the National Institute of Child Health and Human Development (NICHD). Bringing the RIMS product to market would broadly support NIH's mission to improve public health outcomes through strengthening capacity of clinical and translational science.

Project Terms:
Address; Alcohol abuse; Area; base; Behavioral; Behavioral Research; behavioral/social science; Child; Child health care; Clinical; Clinical Data; clinical practice; Clinical Research; Clinical Sciences; Collaborations; commercial application; commercialization; Computer software; cost; cost effective; cost effectiveness; Data Base Management; Data Collection; data management; Data Quality; Data Security; design; Development; Diabetes prevention; Drug abuse; effectiveness research; Ensure; Evaluation; experience; Feedback; flexibility; Foundations; Goals; Health; health economics; Health Insurance Portability and Accountability Act; Healthcare; Human; Human Development; implementation research; improved; Individual; innovation; Institutes; Institutional Review Boards; Internet; Letters; Marketing; Measurement; Measures; meetings; Methodology; Methods; Mission; Modification; National Institute of Drug Abuse; National Institute of Mental Health (U.S.); National Institute on Aging; Obesity; Online Systems; Outcome; Participant; Patient Care; Peer Review; Phase; Play; Prevention; Preventive; Principal Investigator; product development; programs; Protocols documentation; public health medicine (field); Publications; Randomized; Recording of previous events; Recruitment Activity; Reporting; Research; Research Activity; research and development; Research Infrastructure; Research Personnel; Research Support; response; Role; satisfaction; Scientific Advances and Accomplishments; Scientist; Services; Small Business Innovation Research Grant; social; success; symposium; System; Technology; Test Result; Testing; Time; tool; Translating; Translational Research; Translations; United States National Institutes of Health; usability; Violence; Work