黄芩苷类脂纳米囊的研制

发布时间：2018-06-28 21:51

  本文选题：黄芩苷 + 类脂纳米囊　； 参考：《山东大学》2014年硕士论文

【摘要】：黄芩苷(baicalin,BA)是从唇形科植物黄芩(Scutellaria baicalensis Georgi)干燥根中提取的一种黄酮类化合物。具有抗菌、抗炎、抗氧化、抗病毒、扩张血管、调节免疫系统等药理作用,在恶性肿瘤、传染病、延缓人体衰老等方面的应用前景非常广阔。黄芩苷在药理安全性、成本效益、毒性等方面的优势,促使许多研究人员对其进行了深入研究。 黄芩苷为难溶性药物,在水中溶解度较小,在碱性条件下易溶解,在酸性溶液中易析出,对光不稳定,且口服生物利用度低,限制了其推广使用。为此,药剂研究者在黄芩苷的制剂方面进行了大量的探索和研究。为改善其口服吸收,本文制备黄芩苷类脂纳米囊(baicalin-lipid nanocapsules, BA-LNC),考察了其理化性质,并进行了大鼠口服给药动力学的研究,探索类脂纳米囊作为黄芩苷口服给药载体的可能性及优势。 用相转化法制备类脂纳米囊,以包封率和载药量为指标,通过单纯形网格法对处方因素进行优化,采用响应面法对实验结果进行处理,得到最优处方为：黄芩苷用量为10mmg,卵磷脂的用量为3Omg,NaCl的用量为34mg,油相、表面活性剂、水三种组分总量为1.97g,其中表面活性剂聚乙二醇单硬脂酸酯(SolutolHS15)的质量百分比为38%,油相辛酸/癸酸三甘油酯(MCT)的质量百分比为12%,蒸馏水的质量百分比为50%。实验结果表明制备的黄芩苷类脂纳米囊包封率为92.58%,载药量为1.69%。在透射电镜下BA-LNC呈类球形,分散良好,无粘连,平均粒径为84.2nm,多分散指数为0.201,Zeta电位为-13.2mV。通过透析法考察了BA-LNC在模拟胃、肠液中的体外释药行为,结果表明制剂在人工胃液及人工肠液中均表现出一定的缓释性,且后者相对前者释放较快。 采用Wistar大鼠研究黄芩苷类脂纳米囊制剂的口服药物动力学,结果显示：BA-LNC制剂相对于黄芩苷混悬液(对照组)在AUC0-12、AUC0-∞、MRT0-12、 MRT0-∞等药动学参数上有明显优势,说明BA-LNC制剂可促进药物的吸收,延长黄芩苷在体内的滞留时间,从而提高黄芩苷的口服生物利用度。
[Abstract]:Baicalin (Baicalinba) is a flavonoid extracted from dried roots of Scutellaria baicalensis Georgi. With antibacterial, anti-inflammatory, anti-oxidation, anti-virus, vasodilation, regulating the immune system and other pharmacological effects, in malignant tumors, infectious diseases, delaying human aging and other aspects of the application prospects are very broad. The advantages of baicalin in pharmacological safety, cost-effectiveness and toxicity have prompted many researchers to study it in depth. Baicalin is difficult to dissolve in water, easy to dissolve in alkaline condition, easy to precipitate in acid solution, unstable to light, and low in oral bioavailability, which limits its popularization and application. To this end, pharmaceutical researchers in the preparation of baicalin carried out a lot of exploration and research. In order to improve the oral absorption of baicalin, baicalin nanoparticles (BA-LNC) were prepared, their physical and chemical properties were investigated, and the kinetics of oral administration of baicalin was studied. Lipid-like nanocysts were prepared by phase inversion method. The encapsulation efficiency and drug load were taken as indexes. The prescription factors were optimized by simplex mesh method and the experimental results were processed by response surface method. The optimum formulation was as follows: baicalin was 10mmg, lecithin was 3Omg NaCl, oil phase, surfactant, and so on. The total content of three components of water is 1.97 g. The mass percentage of surfactant polyglycol monostearate (Soluto HS15) is 38. The mass percentage of oil phase octanoic acid / triglyceride decanoate (MCT) is 12 and that of distilled water is 50. The results showed that the encapsulation efficiency of baicalin nanoparticles was 92.58 and the drug load was 1.69. Under transmission electron microscope, BA-LNC was spherical with good dispersion and no adhesion. The average particle size was 84.2 nm, and the polydispersity index was -13.2 MV. The in vitro release behavior of BA-LNC in simulated stomach and intestinal fluid was investigated by dialysis. The results showed that BA-LNC showed a certain sustained release in artificial gastric juice and artificial intestinal fluid, and the latter released more quickly than the former. The oral pharmacokinetics of baicalin lipid nanocysts in Wistar rats was studied. The results showed that compared with baicalin suspension (control group), the oral pharmacokinetics of baicalin was significantly superior to that of baicalin suspension (control group) in the pharmacokinetic parameters such as AUC0-12 AUC0- 鈭，

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