Development of Research Grade Goldenseal Phase II

Products produced from Hydrastis canadensis L. commonly known as goldenseal are among the top 20 herbal supplements sold in the U.S. and the sixth most used botanical in children. However, there has never been a controlled clinical study to evaluate its safety and effectiveness for any indication primarily due to the lack of a well characterized, standardized product. This lack of data not only presents a challenge to public health but also impedes economic development of the plant as a viable crop option for growers as well as environmental efforts to conserve the plant through cultivation. The goal of this project is to develop a series of research grade products from Hydrastis suitable for use in NIH funded pre-clinical and clinical studies. Phase I demonstrated the feasibility of using biological activity as a complementary marker for product standardization purposes and determined the optimal combination of plant parts which result in the maximum amount of activity with minimal adverse effects. In PhaseII, OrganiPharm, LLC will collaborate with a highly skilled and complementary team of scientists to build on these initial efforts by developing a prototype batch of research grade Hydrastis products that have been standardized to produce repeatable bioactivity and sufficiently characterized so as to meet FDA requirements for a botanical product Investigational New Drug application. The standardization method is innovative and based on the theory that berberine, reported to be the primary active compound inHydrastis, is in its least active, most toxic form when isolated from the whole plant matrix and that other compounds in the plant work synergistically to increase activity and reduce toxicity. Therefore less berberine is needed in the whole plant productto achieve a comparable level of bioactivity allowing product activity to be indexed to that of reference standard, i.e. 0.5, 1.0, 1.5 times the standard. Phase II will 1) Validate that starting material from disparate sources is similar in chemical composition and bioactivity to the material used in Phase I, 2) Establish a prototype batch of research grade USDA National Organic Program certified Hydrastis in each of four formulations, a) powder, b) tincture, c) solid extract, and d) powdered root extractplus a placebo for each, 3) Chemically characterize the batches in detail and conduct stability testing, 4) Establish a Drug Master File (DMF) for each of the Hydrastis formulations to be available for reference by researchers developing study protocols requiring a Botanical Product Investigational New Drug application. This project will have a significant impact on the herbal supplement industry by offering a model for increasing the reliability of Hydrastis products through biological standardization. Theproject will have a significant impact on public health in this country by facilitating the development of safety and efficacy data for a widely used botanical product that would otherwise been impossible to achieve.