| ObjectiveModern pharmacological studies confirmed that Danshen Decoction can dilate coronary artery and surrounding blood vessels and increase the blood flow of coronary artery, which may cause lower blood pressure. When the heart function insufficiency, it can improve the myocardial contraction force, promote the collateral circulation and the redistribution of blood flow in the body, while reducing plasma viscosity in patients with coronary heart disease, accelerating erythrocyte electrophoresis rate, improving red blood cell volume and microcirculation.Thus it have a good therapeutic effect for the blood of patients with coronary heart disease, with the tendency of"sticky, polyethylene and stagnation", considerable potential for development.For making the Danshen Decoction formula develop into a new formulations of safety, effectiveness and easy to use, this subject selection it as the research object, by adopting the combination of chemical and pharmacological train ideas, make the extraction index as the breakthrough point, using new technology of Supercritical Fulid Extraction (SFE-CO2) and Uniform Experimental Design method to optimize the processes, while using Isoprenaline(ISO) to induce acute myocardial ischemia in mice model for extracting method for preliminary screening, at the same time, the preparation into a proprietary Chinese medicine prescriptions,micro pill preparation. Under the systematic studies of Danshen Decoction formula, it can provide a certain amount of experimental research for the development of safe, effective and easy to use in the treatment of coronary heart disease.MethodsOn the basis of preliminary laboratory research, systematic summary and relevant literature, this subject adopts the the traditional and supercritical fluid extraction methods to extract formula, HPLC, GC and other methods are applied to determine the content of the index components, using uniform experimental design to optimum the extraction methods, adapting isoprenaline induced acute myocardial ischemia in mice model to test electrocardiogram (ECG) ST-segment elevation values, serum CK and LDH activity as indexes for each extraction method's samples preliminary comparative study to determine the best extraction method. Study on the making and molding process for the micro pill preparation and set up the pharmacodynamic verification for the micro pellet of Danshen Decoction.Results1. The water soluble ingredients danshensu, protocatechuic aldehyde and Sal B are instable, degradation of the salvianolic acid B accorded with the first-order kinetics equation, and the Arrhenius equation is 1gK=-2485/T+5.606.2. Determinating the extraction methods by Uniform Experiment Design methods, as fllows. ?The optimum extraction process of boiling method is 12 times the amount of water, extracted 2 times and 1.5h per times;?The optimum extraction process of the supercritical extraction combined with the dregs of boiling water is extraction pressure is 30Mpa, extraction temperature is 45?,and 2.5h per time, the method of dregs is 10 times the amount of water,2 times, and 0.5h per time;?The optimum extraction process of the supercritical extraction combined with ethanol extraction is extraction pressure 30Mpa, extraction temperature is 45?,and 2.5h per time, the method of dregs alcohol extraction processis 95% ethanol,10 times the amount of ethanol,2 times and 0.5h per time.3. The samples of different extraction methods for each treatment group isoproterenol-induced myocardial ischemia in mice have varying degrees of protection,which can reduce the value of ECG's ST-segment elevation, lower the serum CK and LDH activity.4. This studies make the micro pellet of Danshen Decoction and molding process to determine the pellet preparation simple and feasible method for preparing a composition in which the prescription as fllows, total extract (supercritical extracting+dry cream powder of dregs alcohol extracting):MCC Lactose:6% HPMC=1:2:1:2.5 (ie,drug loading of 25%), the total amount of material is 88.24g. Molding processis extrusion speed of 20Hz, rounded speed of 10Hz, spheronization time 7min.5. Established the fingerprint of micro pellet of Danshen Decoction by HPLC and GC-MS and compared with the original extract, its characteristic peak is similar.6. The micro pellet of Danshen Decoction can reduce the myocardial ischemia mice S-T segment elevation, serum CK and LDH activity at a certain extention.ConclusionThis studies using the modern new technology and new methods, the combination of chemical and pharmacological research ideas and research methods of micro pill preparations of Chinese medicine Danshen dection preliminary pharmaco dynamics index component extraction method, prescriptions and micro pill preparation for preliminary discussion and research, through above experimental research, we can draw the following conclusions:1. Preliminary research findings water-soluble ingredients Dan phenolic acid B is not stable, and the degradation accorded with the first-order kinetics equation, so we should pay attention to the heating temperature and heating time;2. The combination of chemical and pharmacological research indicate that the optimum extraction process of formula is the supercritical extraction combined with ethanol extraction.3. Comparing the micro pellet of Danshen Decoction HPLC and GC-MS fingerprint in extracts and original alignment, which can conclude:the method of extrusion by rolling to product the micro pellet of Danshen Decoction, it can retains the original extract the characteristic composition, micro pill preparation technology is simple and feasible.4. The micro pill preparation has a certain protective effect on myocardial ischemia mice... |
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