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中药有效成分提取及药物微囊化研究
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摘要
中药的优质提取物一直是中药研究的热点。本文研究了一些提取中药优质成分的方法,并对提取的有效成分进行初步活性研究,此外,还对中药的有效成分开展了微囊化研究,并以其他药物的微囊化进行对照。
     本文研究了羊蹄有效成分的甲醇提取法,并对采用该法提取的蒽醌类物质进行分离纯化,所得的三种蒽醌类物质,经浓缩后,通过TLC、红外光谱、高效液相检测,对比相应标准品,确认三种物质分别为:大黄素,大黄酚和大黄素甲醚。在此基础上,设计了抑菌实验,菌种选用白色念珠菌和酿酒酵母菌,结果发现该蒽醌类物质对供试菌种有明显的抑菌活力。
     在黄芪和五味子多糖的提取研究中,采用醇碱提取法。通过单因素实验确定最佳提取工艺。以水提取法和碱提取法做对比,证实该法的提取率明显高于另两种方法。提取的多糖经活性实验证明,具有清除羟自由基和氧自由基的活性。抑菌实验证明,该法提取的五味子多糖具有抑菌活性。在此基础上,开展了溶剂对黄芪细胞壁组织影响的研究。通过各种检测实验,证明了醇碱溶液通过破坏细胞壁组织,提高提取率的作用机理。
     中药的有效成分对人体的作用,有些会对胃产生刺激,而有些会在胃酸的作用下失活,还有些需经缓释方能到最佳效果。为此,本文对中药的有效成分进行了微囊化研究,以可降解的聚乳酸为囊材,市售人参皂甙Rg3纯品为包埋对象开展实验,同时以红霉素的明胶微囊化研究验证微囊制备工艺。以阿拉伯胶作为修饰剂,设计正交实验,通过溶剂蒸发法,制备人参皂甙Rg3的聚乳酸微囊,平均粒径为40μm,包埋率及收率均高。体外实验显示呈梯度释放,具有缓释效果。以生物可降解明胶为载体,采用乳化交联法制备红霉素的明胶微囊,平均粒径为15.17μm,载药量和包封率均理想。体外实验也显示了良好的缓释效果。
In this thesis, the traditional Chinese medicine was the main study object. The optimum methods to extract the high quality components were developed. The activity of the effective components extracted from the traditional Chinese medicine was studied. In addition, experiment studies on the microencapsulation of two drugs were carried out.
     We utilized methanol to extract the effective components of Rumex japonicus, which was a new method based on traditional solution separation. Most anthraquinone and its derivatives could be extracted with this method. We continued to isolate and purify the extraction with TLC separation and silica gel chromatography. Comparing the results, the latter is better. We isolated three types of anthraquinone derivatives. The infrared spectrum analysis of the three concentrated compounds identified their corresponding absorbance. HPLC revealed three types of anthraquinone derivatives: emodin, chrysophanol, and physcion. To detect bacteriostasis activity of the anthraquinone components, we designed bacteriostatic experiment. Candida Aibicans and accharomyces cerevisiae were selected as the target. The two anthraquinone derivatives extracted were detected. The minimum inhibition concentratin(mic) were calculated. This could prove that the anthraquinone and its derivatives from the Rumex had antibacterial activity.
     In this research,we studied the ethanol-alkali extraction method to of astragalus polysaccharides and Schisandra chinensis Baill. The optimum extraction technology was identified by single factor investigation. The extraction rate of ethanol-alkali extraction method is much higher than water extraction and alkali extraction method. According to vitro bioactivity experiment, the polysaccharides extracted by ethanol-alkali solvent had an strong inhibition effect on superoxide radical and hydroxyl radical. And the polysaccharides from Schisandra chinensis Baill had inhibition effect on some test bacteria according to inhibition experiment on vivo bacteria. Meanwhile, the effect of different solvents on the extraction of effective components from the cell wall tissues was studied by the histochemical methods, such as the bare-handed section, swelling ratio, paraffin section, IR spectrum and cell wall component analysis. The results showed that the ethanol-alkali solvent could increase the swelling ratio as well as the swelling speed. The effective components of cell tissues extracted by ethanol-alkali solvent becomes loose shown by the paraffin section. According to the IR spectrum analysis and the results of cell wall tissue component analysis, it was found that the ethanol-alkali solvent could decrease the contents of pectin and hemicellulose in the cell wall to make the wall broken, and therefore the effective components can be extracted easily by the solvent and the extraction rate was increased.
     Ginsenoside is the main drug effective composition and the substance basis of physiological activity on ginseng. In this research, Polylactic acid (PLA) microspheres were prepared by conventional solvent evaporation method and alabum was also first used as a modifier. The preparation method of PLA microspheres was selected by orthogonal designing experiments. The result shows that the microspheres we prepared have relatively uniform diameter, the optimum even diameters is about 2.0-3.0um, and the surface of the microspheres is smooth. We encapsulate gineenoside Rg3 using a biodegradable polylactide(PLA) microsphere. This process was studied by emulsion solvent evaporation method for enhancing solubility and stability of ginsenoside Rg3. The mean diameters of the prepared PLA microspheres containing Rg3 were 40μm. The rate of retention and the recovery rate were all high. Ginsenoside Rg3 release from microspheres was studied by HPLC and detected by UV. It was found that the drug release curve fitted with Model Heller-Baker best. Furthermore,gelatin microspheres were repared by using emulsion chemical-crossline technique. The mean diameters of the gelatin microspheres were 13.72μm.We encapsulated erythromycin using this gelatin microspheres. The mean diameters of this gelatin microspheres containing erythromycin were 15.17μm.The drug loading ratio and encapsulation efficiency were satisfied. The erythromycin-loaded gelatin microspheres showed good release profiles with a nearly constant release in vitro degradation studies.
引文
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