【摘要】：人參果為五加科植物人參PanaxginsengC.A.Mey的成熟果實(shí),也是珍貴的中藥材。人參果具有對(duì)多種疾病防治效果和對(duì)人體滋補(bǔ)強(qiáng)壯作用,在我國(guó)藥用歷史悠久。人參果因其富含人參皂苷和具有顯著的生理活性,已引起國(guó)內(nèi)外學(xué)者的廣泛重視和研究。人參果含有多種化學(xué)成分,主要成分是人參皂苷、多糖、生物堿、揮發(fā)油、氨基酸、無(wú)機(jī)元素以及甾醇等。人參果主要有效成分是人參皂苷,眾所周知人參皂苷在人體內(nèi)的口服給藥生物利用度很低,并且人參皂苷在體內(nèi)消除是非常迅速。本文的目的是通過(guò)新的劑型--脂質(zhì)體,來(lái)提高人參果皂苷的生物利用度,采用前體脂質(zhì)體的劑型,來(lái)提高脂質(zhì)體的穩(wěn)定性,并延長(zhǎng)人參皂苷保藏時(shí)間。我們?cè)O(shè)計(jì)實(shí)驗(yàn)將人參果皂苷前體制成脂質(zhì)體制劑。本文以提高人參果皂苷口服生物利用度為目的,以含量最高的人參皂昔Re為含量標(biāo)準(zhǔn),采用生產(chǎn)可行的乙醇注入法和噴霧干燥法制備人參果皂苷前體脂質(zhì)體,通過(guò)單因素試驗(yàn)考察影響脂質(zhì)體粒徑及包封率的影響因素；并通過(guò)響應(yīng)面優(yōu)化方案確定脂質(zhì)體制備的最佳工藝、處方參數(shù),并對(duì)噴霧干燥法制備的人參果皂苷前體脂質(zhì)體的基本理化性質(zhì)以及初步穩(wěn)定性進(jìn)行了研究,對(duì)脂質(zhì)體的粒徑、包封率、初步穩(wěn)定性進(jìn)行考察,結(jié)果表明人參果皂苷前體脂質(zhì)體的平均粒徑236.1nm,且乙醇注入法制備前提脂質(zhì)體工藝簡(jiǎn)單、穩(wěn)定性高、重現(xiàn)性良好,適合大規(guī)模生產(chǎn)。建立了HPLC測(cè)定人參果皂苷脂質(zhì)體藥物含量的方法,采用透析法分離脂質(zhì)體與游離藥物,建立了包封率的測(cè)定方法,建立了人參果皂苷前體脂質(zhì)體的體外釋放檢測(cè)方法。通過(guò)體內(nèi)藥動(dòng)學(xué)及初步的安全性實(shí)驗(yàn)評(píng)價(jià)人參果皂苷前體脂質(zhì)體制劑的優(yōu)勢(shì)。本論文分別以原料藥及振源片作為對(duì)照藥及陽(yáng)性對(duì)照藥物,對(duì)本實(shí)驗(yàn)室研制的人參果皂苷前體脂質(zhì)體制劑,對(duì)大鼠口服灌胃給藥的藥代動(dòng)力學(xué)進(jìn)行了研究。實(shí)驗(yàn)結(jié)果表明,前體脂質(zhì)體組的Auc0→t值為2082.492±408.33 μg · h · mL-1,片劑組的Auc0→t值為1151.38±198.29μg · h · mL-1,原料藥組的Auc0→t值為733.32±113.82μg·h·mL-1,t-檢驗(yàn)分析有顯著性差異(p0.01),相對(duì)生物利用度分別為180.89%及283.91%；Tmax觀察其它藥動(dòng)學(xué)參數(shù)并沒(méi)有明顯差異(P.005)。通過(guò)小鼠初步體內(nèi)安全性評(píng)價(jià),結(jié)果表明該劑型健康無(wú)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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