| BACKGROUND:Depression is a common mental disease which belongs to one of the ten kinds of major diseases. The incidence rate of mental illness is increased along with the development of society. Due to increased economic burden and pressure, the rate of incidence of depression is rising year by year along with the the disturbance to the surrounding environment. The damage of the depression on the people’s life has drawn great attention of world health organization in medical field. "The major project of important new drug discover" is a large science and technology program which is hosted by the Ministry of science and technology of people’s republic of china. It aims to break through the existing domestic technology, meet the people’s needs of basic drugs, and urged the medicine industry development rapidly and safety. To solve the key technology and method in drug discovery by using the science and technology in home and abroad. The new drug research and development is to solve the problems of the safety and quality in the drug use. The drugs with independent intellectual property rights were be obtained through the process of drug discovery, which could enhance the competitiveness of enterprises and make enterprises gain the market share. The special project "innovative drug research and development" in the "The major project of important new drug discover" is aimed at the 10 species of major diseases which serious harm to people’s life and health. Through independent research and development to obtain drugs with independent intellectual property rights, large of market share, higher safety, better effect and more economical. Antidepressant research belongs to this scope.In order to solve the side effect problems of western medicine in the treatment depression, our research group has done much research on the famous formula anti-depression component of Xiaoyaosan. All of this work are supported by the major project and three National Fund under the Ministry of science and technology of china. Fufang Chaigui Fang (FFCGF) is composed after two herbal drugs removed from the formula. This project will further to demonstrate the rationality of prescription and preparation of FFCFG, and also control the quality of Fufang Chaigui Fang.OBJECTIVE:1. In order to extract the maximum effective antidepressant components, reduced dose, improve effect and adapt production line, our research investigate the prescription and process of FFCGF.2. In order to control the quality of FFCGF, we establish the fingerprint of anti depressant components of FFCGF, identify the main chemical substances in the medicinal materials and build the content determination method of index components.3. In order to provide pharmaceutical research information for the development of new drugs, we establish the quality control standards of antidepressant effective components of FFCGF.METHODS:1. Analyzing the correlations of effective components of Xiaoyaosan 1HNMR fingerprints and the antidepressant effect, then clear its main efficacy components in Xiaoyaosan. Demonstrate the rationality of the prescription based on the results of Xiaoyaosan 1HNMR spectrum-effect relationship.2. Optimizing technological based on the extract rate and content of ferulic acid and atractylodes lactone Ⅲ.3. Optimize the parameters of the extract and purification process based on the extract rate and content of ferulic acid and atractylodes lactone Ⅲ.4. Establish HPLC fingerprint of effective components of FFCGF and identify the compounds based on the reference substance and crude materials. Establish the analysis methods of ferulic acid and atractylodes lactone Ⅲ.5. Complete the quality standards of FFCGF.RESULTS:1.Confirm the main anti-depressant compound come from Bupleurum, Angelica and Atractylodes; Select ferulic acid and atractylenolide Ⅲ as quality control index; Demonstrate the compound prescription of FFCGF(Bupleurum, Angelica, Atractylodes, licorice, ginger, mint); 2. The process was determined as follow:FFCGF herbs with 8 times amount of 75% ethanol soaking for 30 minutes, and then extraction 1.5 hour at 2 times; Extract enriched to quantitative, 1 times amount ethyl acetate purified for 2 times.3. There were 8 peaks identified in HPLC spectrum. The similarity of common peaks are above 0.8.4. Established TLC identification of ginger and mint; The content of ferulic acid and atractylenolide III are used for quality control.CONCLUSION:1. Screened out the best prescription composition and the optimal process and provide reliable parameters for industrial production.2. The quality control of antidepressant compounds was studied for further development of pharmaceutical technology, content determination of compound reflect the effective and the fingerprint reflects the consistency of product. |
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