注射用促肝细胞生长素溶媒稳定性和生物活性研究  

Study on stability and bioactivity of hepatocyte growth factor for injection in various solvents

作　　者：林柳青[1] 黄博宁 董宴斌 林宝琴 LIN Liu-qing;HUANG Bo-ning;DONG Yan-bin;LIN Bao-qin(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Guangzhou Guobiao Inspection and Testing Co.,Ltd.,Guangzhou 510530,China)

机构地区：[1]广州中医药大学第一附属医院,广州510405 [2]广州国标检验检测有限公司,广州510530

出　　处：《中国新药杂志》2023年第18期1893-1898,共6页Chinese Journal of New Drugs

摘　　要：目的:通过理化实验和细胞实验研究注射用促肝细胞生长素(hepatocyte growth-promoting factor for injection, HGFI)的溶媒稳定性以及与不同材质输液管的相容性,为其临床使用提供科学依据。方法:理化实验:HGFI分别用不同注射液复溶,于0和24 h经/不经聚氯乙烯(polyvinylchloride, PVC)、热塑性橡胶(thermoplastic elastomer, TPE)、热塑性聚氨酯橡胶(thermoplastic polyurethanes, TPU)输液管取样,测定其pH值、蛋白质、澄清度、可见异物、不溶性微粒、摩尔渗透压浓度、含量和高分子物质。细胞实验:HGFI用5%葡萄糖注射液和0.9%氯化钠注射液复溶,于0与24 h取溶液与完全培养基配制成不同浓度的药液,与大鼠肝细胞(BRL)共孵育48 h, CCK-8法检测细胞活力。结果:理化实验:HGFI用5%葡萄糖注射液、0.9%氯化钠注射液、5%葡萄糖氯化钠注射液复溶,室温(26℃)不避光放置0和24 h,经/不经PVC,TPE,TPU材质输液管取样,其pH值、蛋白质、澄清度、可见异物、不溶性微粒、渗透压摩尔浓度、含量测定、高分子量物质均符合《中华人民共和国药典》2020年版的质量标准。细胞实验:正常对照组与HGFI 0 h比较活性相当,与HGFI 24 h比较,放置24 h的HGFI配制药液能观察到BRL细胞活力显著提高,HGFI配制药液对BRL细胞无不良毒性作用。结论:HGFI用5%葡萄糖注射液、0.9%氯化钠注射液、5%葡萄糖氯化钠注射液复溶在24 h内稳定,与PVC,TPE,TPU输液管的相容性良好且与正常对照组比较仍保持良好的生物活性。Objective:To study the stability of hepatocyte growth-promoting factor for injection(HGFI)and its compatibility with different material infusion sets by physical and chemical testing and cell experiment.Methods:HGFI was dissolved with different solvents.Then the solution was sampled at O h and 24 h with or without infusion tube made of polyvinylchloride(PVC),thermoplastic elastomer(TPE),of thermoplastic polyurethanes(TPU)to determine the pH value,protein,clarity,visible foreign bodies,insoluble particles,osmolarity,content and macromolecular substances.HGFI was dissolved with 5%glucose injection or normal saline for 0 h and 24 h,and then diluted with complete medium and co-incubated with rat liver cells(BRL)for 48 h.The cell viability was detected by CCK-8 method.Results:The pH value,protein,degree of clarification,visible foreign bodies,insoluble particles,osmotic molar concentration,content determination,and macromolecular substances of HGFI dissolved with 5%glucose,normal saline,5%glucose and normal saline and sampled via/not via infusion tube of different materials(PVC,TPE,TPU)at O h and 24 h all met the requirements of 2020 edition of Chinese Pharmacopoeia.Compared with the normal control group,HCFI solutions at O h and 24 h not only had no toxic effects on BRL cells,but also significantly increased the viability of BRL cells.Conclusion:HGFI is stable within 24 h with different solvents and has good compatibility with infusion sets of dfferent materials.Moreover,it keeps wonderful bioactivity within 24 h.

关 键 词：注射用促肝细胞生长素 稳定性 细胞活力 生物活性 

分 类 号：R965[医药卫生—药理学]