Core 2 - Botanical Core

该植物学核心的长期目标是建立一个质量保证计划，以便提供 一种标准化的、质量有保证的中药制剂，用于 肠易激综合征的治疗。为了实现这一目标，本核心建议准备和 为项目2和项目3的合作者进行的动物和临床研究提供标准化的草药提取物， 分别进行了分析。为此目的，将获得的原始材料的标准；制备方法 和表征单个草药和多组分配方的化学特征 将建立提取物的质量控制分析和稳定性监测。这个 建议的具体目标包括对个别生药的质量进行验证和标准化 材料.化学标准化用生物活性化合物或标志性化合物的分离和鉴定 目的；制定复合配方的标准化程序；编制 动物研究提取物和用于临床研究的标准化制剂的GMP生产；以及 监测标准化制剂的稳定性。 这些具体目标将实现如下。优质的天然植物药将从可靠的公司获得 商业来源、其种植/采集来源和记录的相关来源信息；以及 他们的身份是通过肉眼/感官和显微检查确认的 药典标准，并根据需要通过DNA分析进行补充。这些草药的样品将进行测试 用于潜在的农药、有毒金属、微生物和真菌毒素的污染，以确保安全。 成分草药的色谱(高效液相色谱和/或LC-MS)图谱将被建立为指纹图谱， 它们将作为复合草药混合物的参照点以及它们自己的身份。至 协助标准化，生物活性成分将通过生物测定指示的乙醇分级来分离 (90%)从复合式中的草药制备的提取物。主要标志性化合物也将被分离出来 根据需要从辅助性草药中提取。将鉴定生物活性化合物或标志性化合物/阐明其结构 可作为定性(高效液相色谱/液质联用)标准的参考，也可用于 复合配方的定量标准化。将为动物准备适当的提取物 由项目2进行研究。与项目2和项目3合作，确定剂量的配方将是 在GMP条件下制备，用于项目3的临床研究。最后，产品的稳定性将被 从生产之日起到临床研究结束时进行实时监测。

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.