摘要
目的筛选交联反应条件，制备强抗酶降解的注射用交联透明质酸钠（HA）凝胶（HA-凝胶），并建立其体外抗酶降解性的测定方法。方法用1，4-丁二醇二缩水甘油醚（BDDE）交联HA制备HA-凝胶，对其体外抗酶降解性的测定方法进行确证；采用正交试验考察6个因素对交联反应的影响，选择最佳反应条件。结果透明质酸酶（HAas）对HA-凝胶体外抗酶降解性测定方法无干扰，HAas在100～500U／mL与产物显色后的吸光度呈线性关系（r=0．9988）。正交试验极差分析和方差分析显示HA的起始反应浓度、BDDE与HA的比例对交联反应具有显著性影响，在氢氧化钠浓度1％、HA平均相对分子质量1．2×10^6反应温度50℃、BDDE与HA的比例为1：10（g／g）、反应时间4h和HA浓度为15％的反应条件下，可得到抗酶降解性最好的HA-凝胶。结论选择适宜反应条件可以制备得到体外抗酶降解性强的HA-凝胶，为进一步开发注射美容和整形产品奠定了基础。
Purpose To screen the optimal conditions of cross-linking reaction, to prepare injectable linked sodium hyaluronate gel （HA-gel）with hight resistance to hyaluronidase （HAas）degradation, and to research on the determination of resistance to HAas in vitro. Methods The HA-gel was prepared using 1,4-butanediol diglycidyl ether（BDDE）, and its resistance to HAas in vitro was determined. The optimal reaction conditions were define by orthogonal test of six factors. Results HAas had no interference in determination of resistance to HAas in vitro. A linear relationship between the concentration of HAas （100 - 500 U/mL）and the absorbance of colored product was shown （ r = 0. 998 8）. The result of orthogonal test by range analysis and variance analysis showed that the initial concentration of HA and the ratio of HA to cross-linking agent were significant factors. The optimal conditions of the parameters were 1% NaOH, 50℃ ,4 h, 10% BDDE/HA and HA with average relative molecular mass of 1.2×10^6 and concentration of 15%. Conclusion The HA-gel excellent resistance to enzymatic degradation can be prepared under optimal reaction conditions, which establishes foundation to develop injectable cosmetic products.
出处
《中国生化药物杂志》
CAS
CSCD
2008年第4期262-265,共4页
Chinese Journal of Biochemical Pharmaceutics
关键词
交联透明质酸钠
正交试验
酶降解
cross-linked sodium hyaluronate
orthogonal test
enzymatic degradation
