5种壳聚糖/卡波姆复合水凝胶的质量鉴定及经皮渗透效果
|
摘要
以食用菌壳聚糖、虾蟹壳聚糖、羧化壳聚糖为原料,卡波姆为辅料,通过两种制备方法研制5种壳聚糖/卡波姆聚电解质复合水凝胶,并对复合水凝胶进行定性鉴别及外观特征、粒度、黏度、溶胀度、稳定性、酸碱度、铅离子含量的鉴定;采用茜素红法、锌试剂法测定壳聚糖经皮累积渗透量.结果表明:5种壳聚糖/卡波姆复合水凝胶的粒径均小于180μm,黏度大于10~5 mPa·s,具有较高的耐热耐寒性,pH呈中性或微酸性,铅离子含量小于10μg·g~(-1),符合《中国药典》的要求,适合人体皮肤使用;除采用直接混合型制备的1%虾蟹壳聚糖/卡波姆复合水凝胶涂抹有颗粒感外,其他4种均具有稠度适宜、细腻有光泽、易于涂抹、有清凉感、稳定性好、黏滞性好、使用安全等优点;食用菌壳聚糖与卡波姆的交联性好于其他4种水凝胶.经皮渗透试验结果表明,茜素红法、锌试剂法均适用于复合水凝胶中壳聚糖含量的测定,0.45μm聚合膜、Strat-M~(TM)皮肤专用膜具有较高的壳聚糖累积渗透量,并随着透皮时间的增加,累积渗透量增大;0.45μm聚合膜可以替代Strat-M~(TM)皮肤专用膜成为壳聚糖透皮给药检测模型.
Five kinds of chitosan/carbomer complex hydrogel were manufactured by 2 methods using edible fungi chitosan, shrimp and crab shell chitosan and carboxylation chitosan as raw materials, and qualities including qualitative identification, appearance characteristics, grain size, viscosity, swelling capacity, stability, pH value and lead ion content were identified refering to the general requirements of gels in Chinese Pharmacopoeia(2015 edition). The cumulative permeability of chitosan was determined using alizarin red and zinc reagent methods. Quality identification results showed that particle sizes of 5 kinds of complex hydrogels were less than 180 microns. The viscosity was greater than 10~5 mPa·s, with relatively high heat and chill resistance. The pH was neutral or slightly acidic. Lead contents were less than 10 μg·g~(-1), which was consistent with the requirement of Chinese Pharmacopoeia and suitable for human body skin. Except hydrogel made by direct mixing method had granular sensation, all other 4 hydrogels were easy to apply, with cool, consistent, lustrous feeling and satisfactory stability and viscosity. Crosslinkage between edible fungi chitosan and carbomer complex hydrogel was the best among them. Percutaneous osmosis experiments showed that alizarin red method and zinc reagent method were applicable methods for determining chitosan content in complex hydrogels. 0.45 μm polymer membrane and Strat-M~(TM) membrane had high cumulative permeability of chitosan, and the cumulative permeability increased along time. 0.45 μm polymer membrane could replace Strat-M~(TM) membrane as a chitosan transdermal drug delivery test model.
Five kinds of chitosan/carbomer complex hydrogel were manufactured by 2 methods using edible fungi chitosan, shrimp and crab shell chitosan and carboxylation chitosan as raw materials, and qualities including qualitative identification, appearance characteristics, grain size, viscosity, swelling capacity, stability, pH value and lead ion content were identified refering to the general requirements of gels in Chinese Pharmacopoeia(2015 edition). The cumulative permeability of chitosan was determined using alizarin red and zinc reagent methods. Quality identification results showed that particle sizes of 5 kinds of complex hydrogels were less than 180 microns. The viscosity was greater than 10~5 mPa·s, with relatively high heat and chill resistance. The pH was neutral or slightly acidic. Lead contents were less than 10 μg·g~(-1), which was consistent with the requirement of Chinese Pharmacopoeia and suitable for human body skin. Except hydrogel made by direct mixing method had granular sensation, all other 4 hydrogels were easy to apply, with cool, consistent, lustrous feeling and satisfactory stability and viscosity. Crosslinkage between edible fungi chitosan and carbomer complex hydrogel was the best among them. Percutaneous osmosis experiments showed that alizarin red method and zinc reagent method were applicable methods for determining chitosan content in complex hydrogels. 0.45 μm polymer membrane and Strat-M~(TM) membrane had high cumulative permeability of chitosan, and the cumulative permeability increased along time. 0.45 μm polymer membrane could replace Strat-M~(TM) membrane as a chitosan transdermal drug delivery test model.
引文
[1] 姜山,史源,朱启忠.壳聚糖文献分析[J].大学化学,2011,26(4):45-48.
[2] 俞清.药用级卡波姆树脂的合成研究[J].化工时刊,2017(12):19-21.
[3] 庄远红,刘静娜,黄家福,等.食用菌壳聚糖—卡波姆复合凝胶的稳定性及其抑菌效果[J].浙江大学学报(农业与生命科学版),2015,41(2):147-152.
[4] 庄远红,林娇芬,潘裕添.羧化壳聚糖—卡波姆复合凝胶的制备及抑菌性研究[J].福建农林大学学报(自然科学版),2015,44(4):408-413.
[5] 祁智,郭敏,向一.双氯芬酸钾壳聚糖凝胶剂的制备与质量控制[J].医药导报,2007,26(1):62-64.
[6] 党云洁,王国杰,杜宇坤,等.斑蝥素胃黏附缓释片的制备与体内外评价[J].中国实验方剂学杂志,2016(21):1-5.
[7] 罗世英,陈华萍.透皮吸收常用的几种实验动物[J].中国药业,2004,13(4):74-75.
[8] 国家药典委员会.中华人民共和国药典(三部)[M].2015年版.北京:中国医药科技出版社,2015.
[9] 孙立苹,杜予民,陈凌云,等.羧甲基壳聚糖水凝胶制备及其在药物控释中的应用[J].高分子学报,2004,4(2):191-195.
[10] 高贵珍,丁黎华,焦庆才,等.锌试剂分光光度法测定壳聚糖含量[J].分析化学,2003,31(12):1 479-1 481.
[11] 高贵珍,焦庆才,陈雷,等.以分光光度法测定复方样品中的壳聚糖含量[J].食品与发酵工业,2003,29(5):49-52.
[12] 邢建国,赵媛,王新春,等.不同基质对复方卡力孜然凝胶剂主要活性成分体外透皮吸收的影响[J].中成药,2011,33(10):1 718-1 721.
[13] 苏杰,张钧寿,吴葆金,等.卡波姆——新型药物辅料[J].中国药学杂志,2000,35(9):579-581.
[14] 孟勇涛,饶丽平.卡波姆在凝胶制剂中使用的问题探讨[J].齐鲁药事,2010,29(12):708-709.
[15] 张晓乐,赵蕊,钱娓.卡波姆基质口腔溃疡乳化型凝胶的研制[J].中国药学杂志,1995,30(7):417-418.
[16] 张志红,高鹏.1%盐酸麻黄素凝胶剂的制备及质量控制[J].天津药学,2001,13(3):45-46.
[17] MONTEMBAULT A, VITON C, DOMAR A. Rheometric study of gelation of chitosan in a hydroalcoholic medium biomaterials [J]. Biomaterials, 2005,26(14):1 633-1 643.
[18] 李选.胶原/壳聚糖复合抗菌敷料膜的制备与表征[D].上海:东华大学, 2017.
[2] 俞清.药用级卡波姆树脂的合成研究[J].化工时刊,2017(12):19-21.
[3] 庄远红,刘静娜,黄家福,等.食用菌壳聚糖—卡波姆复合凝胶的稳定性及其抑菌效果[J].浙江大学学报(农业与生命科学版),2015,41(2):147-152.
[4] 庄远红,林娇芬,潘裕添.羧化壳聚糖—卡波姆复合凝胶的制备及抑菌性研究[J].福建农林大学学报(自然科学版),2015,44(4):408-413.
[5] 祁智,郭敏,向一.双氯芬酸钾壳聚糖凝胶剂的制备与质量控制[J].医药导报,2007,26(1):62-64.
[6] 党云洁,王国杰,杜宇坤,等.斑蝥素胃黏附缓释片的制备与体内外评价[J].中国实验方剂学杂志,2016(21):1-5.
[7] 罗世英,陈华萍.透皮吸收常用的几种实验动物[J].中国药业,2004,13(4):74-75.
[8] 国家药典委员会.中华人民共和国药典(三部)[M].2015年版.北京:中国医药科技出版社,2015.
[9] 孙立苹,杜予民,陈凌云,等.羧甲基壳聚糖水凝胶制备及其在药物控释中的应用[J].高分子学报,2004,4(2):191-195.
[10] 高贵珍,丁黎华,焦庆才,等.锌试剂分光光度法测定壳聚糖含量[J].分析化学,2003,31(12):1 479-1 481.
[11] 高贵珍,焦庆才,陈雷,等.以分光光度法测定复方样品中的壳聚糖含量[J].食品与发酵工业,2003,29(5):49-52.
[12] 邢建国,赵媛,王新春,等.不同基质对复方卡力孜然凝胶剂主要活性成分体外透皮吸收的影响[J].中成药,2011,33(10):1 718-1 721.
[13] 苏杰,张钧寿,吴葆金,等.卡波姆——新型药物辅料[J].中国药学杂志,2000,35(9):579-581.
[14] 孟勇涛,饶丽平.卡波姆在凝胶制剂中使用的问题探讨[J].齐鲁药事,2010,29(12):708-709.
[15] 张晓乐,赵蕊,钱娓.卡波姆基质口腔溃疡乳化型凝胶的研制[J].中国药学杂志,1995,30(7):417-418.
[16] 张志红,高鹏.1%盐酸麻黄素凝胶剂的制备及质量控制[J].天津药学,2001,13(3):45-46.
[17] MONTEMBAULT A, VITON C, DOMAR A. Rheometric study of gelation of chitosan in a hydroalcoholic medium biomaterials [J]. Biomaterials, 2005,26(14):1 633-1 643.
[18] 李选.胶原/壳聚糖复合抗菌敷料膜的制备与表征[D].上海:东华大学, 2017.