摘要
针对葛根素溶解度低、口服生物利用度低下的特点，本文以共沉淀法制备了葛根素磷脂复合物，拟增加其口服吸收。首先对其制备条件进行了优化，并在此基础上较为系统和深入地研究了其物理、化学和生物学特性，对其形成机理进行分析探索。另外，还探索性地采用超临界流体沉淀技术制备了葛根素磷脂复合物，并对四种制备葛根素磷脂复合物的方法进行了理化特性的比较研究。具体内容包括以下5个部分：
一、葛根素的溶解度测定以及磷脂的成分鉴别、含量测定研究
研究结果表明：葛根素属于微溶性药物。采用薄层鉴别的方法以不同极性展开剂展开，确定磷脂中所含的主要成分。以HPLC方法使用C_8柱对磷脂中磷脂酰胆碱(PC)的含量进行了测定，含量为62.6％。
二、葛根素磷脂复合物的共沉淀法制备及其工艺优化
(1) 在优化葛根素磷脂复合物制备条件的系统研究中，首先确定建立了能合理、准确评价葛根素磷脂复合物制备条件的标准即葛根素的结合率，并用其考察反应溶剂、葛根素与磷脂的投料比、反应物浓度、反应时间及反应温度等因素对结合率的影响，采用正交设计试验进行反应条件的优化，经统计分析和验证试验得到以乙醇为溶剂、简单易行的最佳反应条件。
(2) 建立简便准确的紫外分光光度法对葛根素磷脂复合物中葛根素的含量进行测定。
三、共沉淀法制备的葛根素磷脂复合物的理化性质及结构鉴定、形成机理研究
(1) 用扫描电镜(SEM)观察了葛根素磷脂复合物的微观形态，结果表明形成磷脂复合物后，原葛根素晶体的薄片样叠加结构消失，表现为粒子分散更为均匀、表面被类磷脂样物质包裹的结构。X-射线衍射分析结果显示葛根素磷脂复合物表现出无定形特征，葛根素自身的晶体衍射峰完全消失，同时复合物的溶解性能等发生了变化。差热扫描分析(DSC)则显示葛根素的特征吸热峰消失。考察复合物在不同pH值水溶液及不同pH水-正丁醇系统中的表观油／水分配系数，实验结果表明葛根素磷脂复合物改善了葛根素在不同pH值水溶液中的溶解度，在水、0.1mol／L HCI、pH6.8 PBS中分别提高了1.91，1.56和1.84倍，表观油水分配系数也分别提高了1.11，1.25和1.30倍。
(2) 对葛根素磷脂复合物的初步稳定性考察结果表明应在干燥、避光的环境下对复合物进行保存。
(3) 采用红外光谱(IR)、核磁共振光谱(NMR)等对葛根素磷脂复合物进行了结构
In present study, puerarin phospholipids complex (PPC) was prepared by co-precipitation to improve oral absorption of puerarin according to its low solubility and low oral bioavailability. The research focused on the formation mechanism of PPC and its physicochemical and biological characteristics on the basis of optimizing the preparation conditions. The PPC was also prepared by supercritical fluid precipitation (SFP) technique and the physicochemical characteristics of PPC prepared by four different methods were compared. Five main sections were included in this paper:
1、The determination of the solubility of puerarin (Pur) , the component identification and phosphatidylcholine(PC) content determination of phospholipids:
The results showed that Pur is slightly soluble in water. The component in phospholipids is identified by TLC in three developing solution with different polarity. A HPLC method was developed to determine the content of PC in phospholipids by using C_8 column and the content was 62.6%.
2、 The optimization of the reaction conditions and the preparation of PPC by co-precipitation:
(1) New attempts were made to the research of the reaction conditions of PPC, and a reasonable criterion of accurate evaluation was established, by which such actors as solvent, temperature, the ratio of puerarin to phospholipids and the concentration of reactants were examined. The orthographic design was used in the optimization of reaction conditions and the best using absolute ethyl alcohol as solvent with a simple reaction condition was obtained through statistical analysis and proof test.
(2) A UV method was established to determine the content of Pur in PPC accurately and simply.
3、The research on the physicochemical characteristics, the structure confirmation and formation mechanism of PPC prepared by co-precipitation :
(1) The microcosmic form of the PPC was observed by scanning electronic microscope (SEM), the results showed that the cascading flakes structure of the original Pur changed to structure entrapping by phospholipids-like materials with more uniform size. X-ray diffraction showed that the complex exhibited an amorphous characteristic and the crystal diffraction peaks
引文
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