application): The goal of this Phase I/Phase II Fast Track project is to develop an improved St. John's Wort product which can be manufactured in a standardized and reproducible manner. St. John's Wort contains multiple bioactive compounds that have been used in a wide variety of ailments, most notably endogenous depression. The approach involves the use of supercritical fluids and near-critical fluids with and without polar cosolvents such as alcohols (trademarked as SuperFluids). These fluids are gases such as carbon dioxide which when compressed exhibit enhanced thermodynamic properties that can be fine-tuned for rapid and selective extraction of bioactive molecules. In Phase I, optimal conditions for selective SuperFluids extraction of and chromatographic purification of St. John's Wort will be established. In preliminary studies, this was accomplished by following the extraction of bioactive compounds with super critical carbon dioxide with 0 to 20% methanol. The results of Phase I studies will be used to develop a large scale manufacturing process. In a Phase II investigation, the conditions for selective extraction and chromatographic purification of bioactive compounds will be further optimized in terms of mechanical components, enhancement devices and operating parameters. Finally, it is proposed to design, build and test a pilot-scale prototype plant that could operate under cGMP conditions. Paracelsian (Ithaca, NY) will perform serotonin uptake assays on contract.
Among the most widely prescribed antidepressants in the United States are Prozac from Eli Lilly, Zoloft from Pfizer and Paxil from SmithKline Beecham. The worldwide sales of the top selling antidepressants are approximately $4.8 billion. As people experience adverse side-effects from prescription antidepressants, there has been a concomitant rise in the use of St. John's Wort and other herbs as natural anti- depressants. This Phase I/Phase II Fast Track SBIR project should lead to the development of a biologically-enhanced, stable and standardized St. John's Wort product that can be manufactured under cGMP conditions to provide a natural alternative with reduced side effects of Prozac, Pfizer and Paxil, and thus satisfy a burgeoning market demand in the $4.8 billion antidepressant marketplace.
