Core 2 - Botanical Core

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The long term objective of this Botanical Core is to establish a quality assurance program in order to provide a standardized, quality assured herbal preparation of a traditional Chinese medicine formula to be used in the treatment of irritable bowel syndrome (IBS). To achieve this objective, this Core proposes to prepare and provide standardized herbal extracts for animal and clinical studies by collaborators in Projects 2 and 3, respectively. Toward this end, standards for the source materials to be acquired; the methods of preparation and characterization of the chemical profiles of the individual herbs and the multi-component formula extracts; as well as quality control analysis and stability monitoring of the extracts will be established. The specific aims proposed include validation and standardization of the quality of individual crude plant drug materials; the isolation and identification of bioactive or marker compounds for chemical standardization purposes; the development of standardization procedures for the composite formula; the preparation of extracts for animal studies and the GMP production of a standardized preparation for clinical studies; and the monitoring of the stability of the standardized preparation. These specific aims will be achieved as follows. Quality crude botanicals will be acquired from reliable commercial sources, their cultivation/collection origins and relevant sourcing information documented, and their identities authenticated by macroscopic/organoleptic and microscopic examinations with reference to pharmacopoeial standards, and augmented by DNA analysis as needed. Samples of the herbs will be tested for potential contamination with pesticides, toxic metals, microorganisms and mycotoxins to insure safety. Chromatographic (HPLC and/or LC-MS) profiles for the component herbs will be established as fingerprint, which will serve as reference points for the composite herbal mixture as well as for their own identities. To assist in standardization, bioactive constituents will be isolated by bioassay-directed fractionation of EtOH (90%) extracts prepared from herbs in the composite formula. Major marker compounds will also be isolated from adjunctive herbs as needed. The bioactive or marker compounds will be identified/structures elucidated and be employed as references in the qualitative (HPLC/LC-MS) standardization, as well as in the quantitative standardization of the composite formula. Appropriate extracts will be prepared for animal studies by Project 2. In collaboration with Projects 2 and 3, a formulation with a defined dose will be prepared under GMP condition for clinical studies by Project 3. Finally, the stability of the product will be monitored in real time from day of manufacture to the conclusion of the clinical study period.