糖酯的分离制备及其对磷脂型纳米体系稳定性的影响

发布时间：2018-01-27 02:37

  本文关键词： 糖酯 醇质体 脂质体 稳定性 高速逆流色谱　出处：《浙江工商大学》2015年硕士论文　论文类型：学位论文

【摘要】：随着纳米技术和药物控释系统的发展,磷脂型纳米载药体系成为近年来研究的热点。但该体系容易发生聚沉、氧化分解、药物泄漏等,其稳定性差一直是发展中亟待解决的问题。目前,应用于磷脂型纳米体系的稳定剂主要有吐温、聚乙二醇等系列,效果一般。糖酯类化合物作为绿色、安全的两亲性非离子型表面活性剂,已广泛应用于食品、化妆品和医药领域中。研究表明,糖酯还能影响药物的溶解、吸收和渗透性能,大大提高药物生物利用度。另外,某些糖酯类化合物本身具有保湿滋润、消炎抗氧化等药理学功效。 本文采用高速逆流色谱(HSCCC-D15000)和柱色谱联用法成功地从南瓜粉提取物中分离制备了二半乳糖酯、三半乳糖酯和四半乳糖酯；通过进行两次高速逆流色谱(HSCCC-D1200)分别将商品蔗糖酯SE-13分离纯化为蔗糖单酯、蔗糖二酯和蔗糖多酯。采用薄膜超声法制备了醇质体和脂质体,将分离制备的糖酯类化合物作为稳定剂加入醇质体和脂质体这两种典型的磷脂型纳米体系中,通过直接观察法和透射电镜(TEM)法观察其宏、微观形态,马尔文粒度电位仪测定其粒径、多分散系数(PDI)和Zeta电位,高效液相色谱(HPLC)法测定其药物包封率,以及在4℃下贮存1、3、6个月后观察和测定各参数的变化,研究不同糖基数的半乳糖酯和不同酯化程度的蔗糖酯对磷脂型纳米体系稳定性的影响。结果表明：(1)蔗糖酯和半乳糖酯都能一定程度地提高醇质体的稳定性。另外,其稳定性随着蔗糖酯酯化程度的增加以及半乳糖酯糖基数目的增加而提高。综合比较分析,蔗糖多酯提高醇质体稳定性的效果比半乳糖酯好。所制备的蔗糖多酯-醇质体粒径为62.0±4.3nm,Zeta电位为-72.3±4.5mV,在贮存6个月后体系依然澄清透明,各参数变化不大。(2)蔗糖酯同样能够提高脂质体的稳定性,其中蔗糖多酯提高脂质体的稳定性效果优于其他蔗糖酯。所制备的蔗糖多酯-脂质体粒径为84.0±4.2nm,Zeta电位为-52.4±3.4mV,在贮存6个月后体系依然澄清透明,各参数变化不大。 综上所述,糖酯是一种极具潜力的磷脂型纳米体系稳定剂。
[Abstract]:With the development of nanotechnology and drug controlled release system, phospholipid nano-drug delivery system has become a hot topic in recent years. However, the system is prone to coalescence, oxidative decomposition, drug leakage and so on. At present, the stabilizers used in phospholipid nanosystems are mainly Tween, polyethylene glycol and other series, the effect is general. Sugar and ester compounds as green. Safe amphiphilic Nonionic surfactants have been widely used in the fields of food, cosmetics and medicine. Studies have shown that carbohydrates can also affect the dissolution, absorption and permeability of drugs. In addition, some sugar and ester compounds themselves have moisturizing, anti-inflammatory, anti-oxidation and other pharmacological effects. In this paper, high speed countercurrent chromatography (HSCCC-D15000) and column chromatography were used to separate and prepare digalactyl ester, trigalactose ester and tetragalactose ester from pumpkin powder extract. The commercial sucrose ester (SE-13) was separated and purified to sucrose monoester by two high speed countercurrent chromatography (HSCCC-D1200). Sucrose diesters and sucrose polyesters were prepared by thin-film ultrasonic method. The glycosylates and liposomes were added to the two typical phospholipid nanosystems as stabilizers. The macroscopical and microscopic morphology were observed by means of direct observation and transmission electron microscopy (TEM). The particle size, polydispersity coefficient (PDI) and Zeta potential were measured by Ma Erwen particle size potentiometer. High performance liquid chromatography (HPLC) HPLC method was used to determine the drug encapsulation efficiency, and the changes of the parameters were observed and determined after storage at 4 鈩，

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