摘要
目的:考察相对分子质量(Mr)及取代度对寡聚精氨酸壳聚糖(CS-R9)体外透皮吸收作用的影响。方法:分别以低、中、高Mr的壳聚糖(LCS、MCS、HCS)为原料,合成具有相近取代度的LCS-R9、MCS-R9、HCS-R9;以LCS为原料,通过改变CS与R9的摩尔比,合成具有不同取代度的LCS-R9-1、LCS-R9-2、LCS-R9-3;以替硝唑(TNZ)为模型药物,采用Franz扩散池法,考察各种CSR9的体外透皮促进作用。结果:经过FTIR、1H-NMR的图谱分析,可以确定本实验所合成的LCS-R9-1、MCS-R9、HCS-R9、LCSR9-2、LCS-R9-3的取代度分别为2.30,2.17,2.20,8.05,15.87;与空白组、氮酮组、LCS组、R9组、LCS+R9组等对照组相比,LCSR9-1对TNZ有明显的透皮促进作用(P<0.05);当取代度相似,CS的Mr不同时,12 h之内,LCS-R9-1与HCS-R9的促进作用相似,均明显大于MCS-R9(P<0.05);12-24 h,HCS-R9的作用有下降趋势,但与LCS-R9-1比较,差异无统计学意义(P>0.05);当CS的Mr相同,而取代度不同时,21 h内,促进作用随着取代度的增加而增加,之后,则呈相反趋势。结论:Mr及取代度对CS-R9的透皮吸收促进作用有较大影响,值得进一步研究其体内作用规律及相关机制。
Objective： To study the effect of molecular weight and degree of substitution（ DS） of chitosan-poly-arginine（ CS-R9） on transdermal penetration enhancement in vitro. Methods： Low molecular CS,medium molecular CS or high molecular CS was respectively used to synthesize CS-R9 with different molecular weight（ LCS-R9-1,MCS-R9 and HCS-R9）. Low molecular CS was used to synthesize CS-R9 with various degree of substitution by changing the mole ratio between R9 and CS（ LCS-R9-1,LCS-R9-2 and LCS-R9-3）. The in vitro transdermal penetration enhancement of the different CS-R9 on tinidazole（ TNZ） was studied using Franz diffusion cells. Results：According to the results of FTIR and1H-NMR,a series of target CS-R9 were synthesized including LCS-R9-1 with the DS of 2. 30,MCSR9 with the DS of 2. 17,HCS-R9 with the DS of 2. 20,LCS-R9-2 with the DS of 8. 05 and LCS-R9-3 with the DS of 15. 87. Compared with the blank control group,Azone group,LCS group,R9 group and LCS ＋ R9 group,LCS-R9-1 could enhance the in vitro transdermal penetration of TNZ significantly（ P〈0. 05）. When the DS was unchanged,LCS-R9-1 and HCS-R9 showed similar enhancement in the first 12 h,and the effects were both higher than that of MCS-R9（ P〈0. 05）. The enhancement of HCS-R9 was decreased during 12-24 h,while compared with that of LCS-R9-1,the difference was not notable（ P〉0. 05）. When the molecular weight of CS was unchanged,the effect was increased with the rise of DS in the first 21 h,however,after that,the effect was decreased with the rise of DS. Conclusion：Molecular weight and DS both have significant effect on the in vitro transdermal penetration enhancement of CS-R9,and it is valuable to further study the in vivo transdermal penetration enhancement of CS-R9 and underlying mechanisms.
出处
《中国药师》
CAS
2014年第12期1996-2000,共5页
China Pharmacist
关键词
壳聚糖
寡聚精氨酸
相对分子质量
取代度
透皮吸收促进作用
Chitosan
Poly-arginine
Molecular weight
Degree of substitution
Transdermal penetration enhancement
