The screening of a complex mixture of analytes is not always successful in sensitive screens for specific activities. Often, specific activities are masked by interfering compounds or false positives are given by ubiquitous compounds that interact with all screens. This problem can be resolved by purification of the analytes. Such an approach is not only cost-prohibitive but will also result in biasing the isolation of analytes tha occur in higher concentrations. Conventional organic solvents are not always ideal for biomass extractions. These solvents can be difficult to remove from the compounds potentially exhibiting bioactivity and, thus can mask bioactivity in an assay. In order to enhance the drug and dietary supplement discovery process, we have developed and patented processes for the polarity-guided fractionation of plants and microbes (Castor et al., 1998, 2003) using supercritical fluid solvents. The overall goal of this research project is to develop a commercial, user-friendly SuperFluidsTM CXF fractionator that can be utilized by researchers at universities and pharmaceutical companies to facilitate the drug discovery and nutraceutical product development process. The primary Phase I object is to design a parallel processing CXF fractionator, and to construct and test a single unit CXF prototype that can process samples in accordance to a pre-defined sequentially increasing-polarity protocol. The unit will have the capability to rapidly produce partially purified natural product molecules from terrestrial plants and marine microorganisms, for example, 6 varying polarity fractions in about 1 hour. In Phase I, we plan to design SuperFluidsTM CXF prototypes, construct key components of the prototypes, and test these components. In Phase II, we plan to complete the hardware and software design of the SuperFluidsTM fractionation unit, assemble single and parallel processing Alpha-site units, test the units at a Beta-site, and redesign and reconstruct as necessary to eliminate bugs and increase user-friendliness. In Phase III, OEM companies will manufacture commercial units. In Phase III, we plan to sell SFS fractionation units, which will include license to utilize the SFS-CXF technologies and equipment, to researchers and product developers at universities as well as nutraceutical, food, pharmaceutical and biotechnology companies.

Public Health Relevance

Per NCCAM, NIH's RFA-AT-14-001, Methods Development in Natural Products Chemistry (SBIR)(R43): Natural products are essential sources of medicines. The World Health Organization estimates that ~80% of the world's population relies on traditional medicines made from natural products. The modern pharmaceutical industry is also dependent on plant-based medicines, with as much as 50% of all drugs based on natural products or derived from a natural product origin. Clearly, plants and other natural products offer excellent sources of health- promoting medicines. Thus it is extremely important that our capacity is enhanced to further examine these traditional modalities and achieve a solid scientific understanding of their potential health benefits. Nonetheless, substantial problems exist in identifying and understanding natural products and their bioactivity. While the potential for natural products in health and wellbeing is clear, the challenges that hamper the full utilization of these resources are many, with the greatest hurdle simply being the enormous amount of time and effort required for structure identification and characterization of the mechanisms by which natural products exert their pharmacological activity. Improvements in collection, bioassay, isolation, purification, de-replication, yield and supply of natural products are possible. While advances have been made to help overcome these hurdles, there exist many new untapped technological resources that may improve natural products research methodologies. The overall goals of the proposed R&D program are to design and develop equipment for the rapid and selective polarity-guided fractionation of secondary metabolites and other bioactive constituents from plants and microbes in a cost-effective manner. This process has been demonstrated to be unique in increasing the recovery and diversity of bioactive secondary metabolites, reducing interference from nuisance compounds and minimizing background noise in sensitive enzymatic and molecular-based screens. Such equipment will also have utility in the rapid generation of natural product libraries for the discovery of human and animal therapeutics, the isolation of bioactive compounds from plants and microbes, and the potential establishment of manufacturing protocols.

National Institute of Health (NIH)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZAT1)
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Williamson, John S
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Aphios Corporation
United States
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