| With lowering lipid and blood pressure, catharsis, eyesight and other effects, Semen Cassiae is a traditional Chinese medicine commonly used in clinical. In this paper, preparation technology of Semen Cassiae prescription granules, pharmacological activities of granules, changes of composition during preparation process and kinetic mechanism of the extraction process were studied.(1) In this part, the UV-vis spectrophotometric determination method on total anthraquinones of Semen Cassia was established. This method is simple, accurate and reliable. Indicated by the content of total anthraquinones, water extraction, ethanol extraction and microwave-assisted extraction were optimized respectively by orthogonal tests based on their single factor tests. The yields of total anthraquinones by the best extraction technologies of the different solvents extraction methods were compared. Ethanol extraction is the best, the extraction rate is 94.91%, the rate of water extraction is 27.55%. The yields of total anthraquinones by different heating modes in ethanol extraction process were compared. The extraction rate of ethanol extraction by normal heating mode is 94.91%, the rate of microwave-assisted extraction is 79.11%. Ethanol extraction by normal heating mode is choosed as the extraction method in the preparation process of Semen Cassiae prescription granules. The optimum extraction process is as follows:extraction temperature was 80℃, reflux extraction with 8-fold 70% alcohol for 2 times,1.5h every time, the granularity of Semen Cassiae power was 40 mesh sieve.(2) The route of separation and purification of total anthraquinones in Semen Cassiae by macroporous resin was obtained. In this part, from the AB-8, D-101-I, DA-201, DM-130, DM-301, NKA-II and NKA-9 seven macroporous resins, DM-130 was choosed to separate and purify the total anthraquinones of Semen Cassiae. Extract concentration, pH, flow rate, different eluants, eluants of different ethanol concentration and other factors were investigated. The adsorption and desorption crafts of DM-130 macroporous resin were optimized. The appropriate adsorption conditions is:the extract concentration 0.4g/mL, pH 7～8, flow rate 2BV/h, the liquid volume and the resin weight ratio of 10:1; the appropriate desorption conditions is:the 70% ethanol used as eluant and the concentration of NaOH is 0.025 mol/L, and the flow rate is 2BV/h. By DM-130 macroporous resin confirmatory test under the best adsorption and desorption conditions, the total anthraquinones of Semen Cassiae transfer rate can reach nearly 60%, and the process is stable.(3) The technologies of spray drying, vacuum drying and freeze drying was established. The water absorption and water soluble capability of products treated with the three drying methods were investigated. The total, dissociative and conjugated anthraquinones of the three kinds of products were determined. The order of water absorption capability is:freeze drying, vacuum drying and spray drying. The order of soluble capability is:spray drying, freeze drying and vacuum drying. Compared the anthraquinone content of the three kinds of drying products, the total and conjugated anthraquinones content of vacuum drying approach freeze drying, and they are higher than spray drying. The content of dissociative anthraquinone in spray drying product is the highest.(4) The transfer rate changes of total anthraquinones in the preparation process of Semen Cassiae prescription granules were studied. The transfer rates of total anthraquinones during the preparation process of Semen Cassiae prescription granules were:the yield of ethanol extraction was 94.91%, the yield was 68.15% after alcohol precipitation, the yields were 69.19%,62.35% and 59.68% by vacuum, freeze, and spray drying respectively. The stage of alcohol precipitation caused the biggest loss of total anthraquinones, the loss rate was up to nearly 30%. Among the three drying methods, spray drying caused the biggest loss of total anthraquinones, followed by freeze drying, vacuum drying had little impact. The chromatographic fingerprints of original medicine and granules treated with the three drying methods were obtained by RP-HPI-C. According to retention time, data were analysed by fingerprint similarity evaluation software to compare the similarity of the samples. The similarity of original herbs, vacuum-dried and freeze-dried granules was above 0.98, the similarity of spray-dried granules was 0.7046. The results showed that vacuum drying and freeze drying methods have little destruction on the composition of the samples, spray drying method has a certain degree of destructive effect on the samples.(5) The pharmacodynamic of Semen Cassiae prescription granules and its traditional decoction was compared by laxative test and lipid test. In the intestinal propulsion experiments, the three kinds of Semen Cassiae prescription granules can increase the intestinal movement in normal mice, and they have similar effect with the traditional water extraction. The three kinds of granules were used in constipation mice. The results showed that the spray, freeze, vacuum drying granules can be reserved the purgative function, and have a trend of being better than the traditional water extraction group. Among these granules, the purgative effect of freeze drying is best, followed by spray drying and vacuum drying. The three kinds of drying granules were used in hyperlipidemic mice. The results show that all of them have the function of reducing blood lipid, and have a trend of being better than the water extraction group. They can reduce TC, TG and LDL-C, increase HDL-C. Among these granules, the regulating blood lipid effect of freeze drying is best, followed by spray drying and vacuum drying. Considering the lack of freeze drying technology, the characteristics of Semen Cassiae prescription granules and the content of anthraquinones, we choose spray drying in the preparation technology of Semen Cassiae prescription granules, and create its quality standard.(6) According to the non-steady state diffusion process of traditional Chinese medicine extraction, the Fick's second law of diffusion was used to establish the one-component kinetic model(OKM) equation of extracting total anthraquinones and chrysophanol from Semen Cassiae by ethanol. The model can describe the dynamic extraction process of total anthraquinone and chrysophanol from Semen Cassiae. The results showed that the kinetics on the extraction of total anthraquinone and chrysophanol match the first-order rate equation, and the rate-determining step for extraction is the diffusion of total anthraquinone and chrysophanol through particles. The kinetics parameters, such as k(rate constant), Ea (activation energy), y (residual rate of extraction) and t(?)(half life) are obtained from the calculation. Based on two-region mass transfer model, the one-component kinetic model (OKM) equation was optimized and the two-component kinetic model (TKM) equation was developed. The research showed that the regression results of the TKM fit the experimental data well, and the changes of the parameters with temperature have some physical meaning. The TKM can reflect the dynamic mechanism better of the extraction process of total anthraquinone and chrysophanol, which has an important theoretical significance for extracting anthraquinones from Semen Cassiae.This research was conducted under the basic theory of traditional Chinese medicine. It combined analytical chemistry, physical chemistry, Chinese medicinal chemistry, Chinese medicine preparation, pharmacology, statistics and other disciplines to explore the preparation technology, composition changes and kinetic mechanism of the extraction process of the Semen Cassiae prescription granules. It can provide a practical and theoretical basis for prescription granules research. |
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