人参果皂苷前体脂质体的研制

发布时间：2019-05-28 23:00

【摘要】：人参果为五加科植物人参PanaxginsengC.A.Mey的成熟果实,也是珍贵的中药材。人参果具有对多种疾病防治效果和对人体滋补强壮作用,在我国药用历史悠久。人参果因其富含人参皂苷和具有显著的生理活性,已引起国内外学者的广泛重视和研究。人参果含有多种化学成分,主要成分是人参皂苷、多糖、生物碱、挥发油、氨基酸、无机元素以及甾醇等。人参果主要有效成分是人参皂苷,众所周知人参皂苷在人体内的口服给药生物利用度很低,并且人参皂苷在体内消除是非常迅速。本文的目的是通过新的剂型--脂质体,来提高人参果皂苷的生物利用度,采用前体脂质体的剂型,来提高脂质体的稳定性,并延长人参皂苷保藏时间。我们设计实验将人参果皂苷前体制成脂质体制剂。本文以提高人参果皂苷口服生物利用度为目的,以含量最高的人参皂昔Re为含量标准,采用生产可行的乙醇注入法和喷雾干燥法制备人参果皂苷前体脂质体,通过单因素试验考察影响脂质体粒径及包封率的影响因素；并通过响应面优化方案确定脂质体制备的最佳工艺、处方参数,并对喷雾干燥法制备的人参果皂苷前体脂质体的基本理化性质以及初步稳定性进行了研究,对脂质体的粒径、包封率、初步稳定性进行考察,结果表明人参果皂苷前体脂质体的平均粒径236.1nm,且乙醇注入法制备前提脂质体工艺简单、稳定性高、重现性良好,适合大规模生产。建立了HPLC测定人参果皂苷脂质体药物含量的方法,采用透析法分离脂质体与游离药物,建立了包封率的测定方法,建立了人参果皂苷前体脂质体的体外释放检测方法。通过体内药动学及初步的安全性实验评价人参果皂苷前体脂质体制剂的优势。本论文分别以原料药及振源片作为对照药及阳性对照药物,对本实验室研制的人参果皂苷前体脂质体制剂,对大鼠口服灌胃给药的药代动力学进行了研究。实验结果表明,前体脂质体组的Auc0→t值为2082.492±408.33 μg · h · mL-1,片剂组的Auc0→t值为1151.38±198.29μg · h · mL-1,原料药组的Auc0→t值为733.32±113.82μg·h·mL-1,t-检验分析有显著性差异(p0.01),相对生物利用度分别为180.89%及283.91%；Tmax观察其它药动学参数并没有明显差异(P.005)。通过小鼠初步体内安全性评价,结果表明该剂型健康无毒。
[Abstract]:Panax quinquefolium fruit is the mature fruit of Panax ginseng PanaxginsengC.A.Mey, and it is also a precious Chinese medicinal material. Ginseng fruit has a long medicinal history in China because of its preventive and therapeutic effects on many kinds of diseases and its nourishing and strengthening effect on human body. The fruit of Panax quinquefolium has attracted extensive attention and research by scholars at home and abroad because of its rich in ginsenosides and its remarkable physiological activity. Ginseng fruit contains a variety of chemical components, the main components are ginsenosides, polysaccharides, alkaloids, volatile oil, amino acids, inorganic elements and sterols and so on. The main active component of Panax quinquefolium is Panax quinquefolium. It is well known that the bioavailability of Panax quinquefolium in human oral administration is very low, and the elimination of Panax ginseng saponins in vivo is very rapid. The purpose of this paper is to improve the bioavailability of ginsenosides through a new dosage form, liposomes, and to improve the stability of liposomes and prolong the storage time of ginsenosides by using the dosage form of proliposomes. We designed the preparation of liposomes by the pre-system of ginseng fruit soap glycosides. In order to improve the oral bioavailability of ginseng fruit soap glycosides and the highest content of ginseng soap shake Re as the content standard, the preparation of ginseng fruit soap glycosides proliposomes was prepared by ethanol injection method and spray drying method in order to improve the oral bioavailability of ginseng fruit soap glycosides. The factors affecting the particle size and entrapment efficiency of liposomes were investigated by single factor test. The optimum preparation process and prescription parameters of lipid system were determined by response surface optimization scheme, and the basic physical and chemical properties and preliminary stability of ginseng fruit soap glycoside proliposomes prepared by spray drying were studied, and the particle size of liposomes was studied. The encapsulation efficiency and preliminary stability were investigated. The results showed that the average particle size of panaxanthin proliposomes was 236.1 nm, and the preparation of liposomes by ethanol injection method was simple, stable and reproducible, so it was suitable for large-scale production. A HPLC method for the determination of panaxanthin liposomes was established. The liposomes and free drugs were separated by dialysis. The method for the determination of entrapment efficiency was established, and the in vitro release detection method of panaxanthin proliposomes was established. The advantages of panaxanthin precursor liposomes were evaluated by pharmacokinetics and preliminary safety experiments in vivo. In this paper, using raw materials and Zhenyuan tablets as control drugs and positive control drugs, the pharmacokinetics of panaxanthin precursor liposomes developed in our laboratory was studied. The results showed that the Auc0 鈮，

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