【作者】 黄思玲；

【导师】 凌沛学； 娄红祥；

【作者基本信息】 山东大学 ， 药物化学， 2006， 硕士

【摘要】 为了提高透明质酸(hyaluronic acid，HA)的口服生物利用度，更好的发挥其美容保健的功效，以蛋黄卵磷脂(phospholipid，PL)作为吸收促进剂，制备了HA-PL复合物。在考察了制备方法、HA的相对分子质量(M_r)、超声破碎时间、反应时间、HA与PL的配比(w／w)以及HA的浓度等影响因素后，确立了简便易行的制备工艺。即首先利用薄膜分散超声破碎法制备PL水分散液，然后与HA的水溶液混合，恒定温度搅拌一定时间得到复合物。其中HA的M为99.2x10~4，HA的浓度为6mg／mL，HA与PL的配比为1：3(w／w)，冰浴超声时间为10min，37℃下保温时间为6h。 HA-PL复合物与HA在理化性质上存在明显的不同。(1)微观形态：通过透射电镜和原子力显微镜观察，发现HA-PL复合物乳液中PL囊泡出现团聚，聚集在HA的周围，说明两者因产生了一定的作用力而结合在一起。(2)热化学性质：差示扫描量热检测结果显示，复合物中PL的相变吸热峰和氧化分解的放热峰均消失，而HA自身的性质没有明显变化，说明HA对PL具有保护作用，使PL对温度的敏感性降低。(3)红外吸收：红外光谱检测结果表明，HA与PL形成了复合物，其相互作用产生在HA的羧基或酰胺基与PL的极性头部基团之间，属于疏水作用和离子键作用。 在研究HA-PL复合物的口服吸收之前，我们研究了不同M_r和不同剂量的HA生理盐水溶液在大鼠体内的口服吸收情况，并研究了组成HA的两种单糖的口服吸收情况。结果表明，HA口服后的吸收效果与M_r和剂量相关，HA的M_r接近100x10~4，剂量为20mg／kg体重时吸收效果较好。HA口服后可以以单糖和非单糖的形式吸收。单糖口服后在大鼠体内可以合成HA，也证实了外源性HA更多还原

【Abstract】 In order to improve the oral bioavailability of hyaluronic acid (HA) and educe its functions of aesthetic and health care, a complex of HA-PL was prepared with egg lecithin (PL) as absorption enhancer. The preparation technology was established after studying preparative methods, relative molecular mass (Mr) of HA, sonication time, reaction time, the proportion of HA and PL, HA concentration, and so on. The suspension of PL was prepared by the method of film dispersion and sonication firstly. Then the suspension of PL was mixed with HA solution and the complex was obtained after stirring under a constant temperature for a definite time. The preparation technology was as follows: the Mr of HA of 99.2×10~4, the concentration of HA of 6 mg/ml, HA : PL 1:3 (w/w), the time of sonication of 10 min and the incubation time of 6 h under 37℃.The differences between physico-chemical properties of complex and that of HA were obvious. (1) Microscopical appearances: It was found that the vesicles of PL gathered together around HA by transmission electron microscope and atomic force microscope. This phenomenon illustrated that PL combined with HA by some acting force. (2) Thermochemical properties: The results of differential scanning calorimetry demonstrated that the endothermic peak by phase transition and the exothermic peak by oxygenolysis of PL in the complex were both disappeared. But the thermochemical property of HA had no obvious changes. It revealed that HA could protect PL and make the sensibility of PL to temperature lower. (3) Infrared absorption: The results更多还原