以明胶—黄原胶为壁材复凝聚法制备微囊的研究

【作者】 王伟；

【导师】 李强；

【作者基本信息】 黑龙江大学 ， 有机化学， 2014， 硕士

【摘要】 本论文系统地研究了以明胶（G）和黄原胶（XG）为壁材，模型药物川芎油为芯材，采用复凝聚法制备微囊的工艺。以微囊的包封率、抗氧化能力和释放性能为指标，考察了固化温度、复凝pH和载药量等因素对微囊性质的影响。红外光谱（FTIR）和差示扫描量热分析（DSC）证实了明胶的阳离子氨基和黄原胶的阴离子羧基之间发生静电相互作用，形成了明胶-黄原胶复凝物，电导法得到二者发生复凝聚反应的最佳比例为1:1。建立了高效液相色谱法测定川芎油含量的分析方法。采用星点设计-效应面法对明胶-黄原胶微囊的制备工艺进行优化，以包封率×30%+芯材保留率×70%为评价指标，结合单因素实验结果得出最佳的制备工艺条件：明胶和黄原胶浓度分别为20%和1%，载药量为39.23%，复凝pH为3.2，在36℃下用50mL5%的戊二醛固化1h，50℃下干燥。此工艺下制备的微囊在扫描电镜下观察到呈规则的球形，表面致密无孔洞，微囊之间稍有粘连。激光粒度扫描结果显示微囊的粒度分布较窄，粒径均一，范围为10～20μm，平均粒径为13.16±0.09μm。加速实验显示微囊化的川芎油抗氧化能力明显提高。微囊的平均含量为35.70%，包封率为90.99%。本文对明胶-黄原胶微囊进行了大鼠体内药物动力学研究。实验结果表明，川芎油在大鼠体内的吸收符合二室模型，一级吸收，川芎油微囊的血药浓度比较平稳，Cmax降低，Tmax后移。相对生物利用度研究结果表明，川芎油微囊相对于参比样品的生物利用度为100.03%。川芎油微囊的体外释放与体内吸收有较好的相关性。更多还原

【Abstract】 In this paper, we have investigated the preparation process of microcapsules, basedon complex coacervation of the gelatin (G) and xanthan gum (XG) as wall material,model drug Ligusticum wallichii essential oil (LWO) as core material. With theencapsulation efficiency, antioxidant capacity and the release property as the indicatorsto study the influence of crosslinking temperature, pH and drug loading on the thenature of microcapsules.Infrared spectrum (FTIR) and Differential scanning calorimetry (DSC) analysisconfirmed the existence of gelatin-xanthan gum coacervates, which was formed byelectrostatic interaction between the cationic amino of gelatin and the anionic carboxylof xanthan gum, and conductance method obtained the best proportion for the complexcoacervation is1:1. High Performance Liquid Chromatography (HPLC) was establishedto measure the content of LWO.Central composite design/response surface method (CCD-RSM) was used tooptimize the preparation process of gelatin-xanthan gum microcapsules, encapsulationefficiency×30%+70%retention rate of core material as the effect value, combiningwith the single factor experimental results to conclude the best preparation technologyconditions: the concentration of gelatin and xanthan gum were20%and1%,respectively, drug loading capacity was39.23%, complex coacervation pH was3.0~3.5,50mL,5%glutaraldehyde was crosslinking1h at36℃, and then dryed under50℃.Scanning electron microscopy (SEM) observed that the prepared microcapsules showedthe rules of the spherical, surface density without holes, and there is slightly adhesionbetween the microcapsules. Laser particle size scanning results showed that themicrocapsules have a narrower particle size distribution, and uniform particle size (10~20μm), the average particle size was13.16±0.09μm. Accelerated testing showed thatthe antioxidant capacity of microcapsules have improved significantly. The averagecontent of micro capsule was36.20%, the encapsulation efficiency was90.99%. In this paper, gelatin-xanthan gum microcapsules were used to investigate thepharmacokinetics in vivo of rats. Experimental results showd that the absorption ofLWO in rats was conform to two compartment model, first-order absorption, the plasmaconcentration of LWO microcapsules was stabled, Cmaxreduced, Tmaxshifted rearward.In the relative bioavailability research, the bioavailability of LWO microcapsules was100.03%compared to the reference. There has good correlation between the in vitrorelease and in vivo absorption of LWO microcapsules.更多还原