摘要
目的开发一种避免PEP06肽形成凝胶从而消除药物凝胶有害作用的优化方法。方法选用不同溶剂研究溶剂对PEP06肽溶解性的影响;将PEP06肽放入装有氨水和浓盐酸容器内,研究pH对pEP06肽成胶性的影响;改变溶液的浓度,研究浓度对PETO6肽成胶性的影响;通过阳离子交换层析去除PEP06肽中的促成胶物质,解决PEP06的成胶问题。结果溶剂的种类影响PEP06肽的溶解性,在偏碱性的PBS缓冲液(pH=6.45)中药物的溶解性较差,在酸性的2%醋酸(pH=3.01)中溶解较好,溶剂对PEP06肽溶解性的影响可能与pH有关。溶液浓度与成胶性正相关,随着溶液浓度的增加,溶液逐渐地变得黏稠,直至形成凝胶。阳离子交换层析后的PEP06肽不再形成凝胶,推测影响PEP06肽成胶性的因素除了PEP06肽自身结构和上述因素外,溶液中可能还有一种能促进PEP06肽形成凝胶的物质,该物质能通过阳离子交换层析去除。结论确定了溶剂、浓度和pH对PEP06肽成胶性的影响;建立了通过阳离子交换层析解决PEP06肽的黏稠和成胶问题的方法,使得高浓度PEP06肽溶液能够通过微孔滤膜过滤,为大规模生产提供了技术支撑。
Objective To develop an optimized method to avoid the gelation of PEP06 peptide and eliminate the harmful effect of drug gelatinization.Methods Different solvents were used to examine the effect of solvent on the solubility of PEP06 peptide.PEP06 peptide was placed in a corn tainer containing ammonia and concentrated hydrochloric acid to study the effect of pH on the gela-tion of PEP06 peptide.The concentration of solution was changed to study the effect of concentration on the gelation of PEP06 peptide.Cation exchange chromatography was used to remove the gel-forming substance in PEP06 peptide to solve the gelation of PEP06.Results The type of solvent affected the solubility of the PEP06 peptide.The solubility of the PEP06 peptide was poor in alkaline PBS buffer(pH=6.45)and was good in 2%acetic acid(pH=3.01).The effect of solvent on solubility of PEP06 peptide was related to pH.The solution concentration was directly related to the gel-forming property,and the solution gradually became viscous to form a gel as the solution concentration increased.After purification by cation exchange chromatography,PEP06 peptide did not form a gel.It was indicated that,in addition to the structure of PEP06 peptide and the above-mentioned factors,there was a substance in PEP06 peptide solution which promoted the formation of gel and could be removed by cation exchange chromatography.Conclusion The effect of solvent,concentration and pH on the gelation of PEP06 peptide was determined.A method for solving the viscosity and gelation of PEP06 peptide solution was established by cation exchange chromatography.By using the method,the high-concentration PEP06 peptide solution can be filtered through a microporous membrane,which provides technical support for large-scale production.
作者
陈奕冰
郭帅利
董兴丽
刘兴汉
王志国
张丽秋
CHEN Yibing;GUO Shuaili;DONG Xingli;LIU Xinghan;WANG Zhiguo;ZHANG Liqiu(Department of Pharmacology,Harbin Medical University,Harbin,150081,China;Department of Biopharmaceutics,Harbin Medical University,Harbin,150081,China;Department of College of Biochemistry and Molecular Biology,Harbin Medical University,Harbin,150081,China;Experimental Teaching Center,Basic Medical College,Harbin Medical University,Harbin,150081,China)
出处
《医学分子生物学杂志》
CAS
2020年第2期135-141,共7页
Journal of Medical Molecular Biology
基金
黑龙江省卫生计生委科研课题(No.2017-160)。