微针贴片的环氧乙烷熏蒸灭菌方法探讨  

Discussion on Sterilization Method for Phase Transition Microneedle Patches

作　　者：张寒莹 董晓陶 陈吉丽 吴飞[1] 金拓[1] ZHANG Hanying;DONG Xiaotao;CHEN Jili;WU Fei;JIN Tuo(School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240)

机构地区：[1]上海交通大学药学院,上海200240

出　　处：《中国医药工业杂志》2018年第12期1690-1694,共5页Chinese Journal of Pharmaceuticals

摘　　要：微针透皮贴片是目前最有可能实现生物大分子药物高效、精准非注射给药的新型制剂。微针贴片虽然只穿透表皮层,在真皮层释药,并不完全刺透皮肤,不造成皮肤撕裂,但在药审中仍作为注射剂处理,建立其灭菌方法成为必须。本研究采用的相转化微针是利用冷冻微晶交联机制制备的,以微晶域作为交联点的针体基质使细菌或病毒等颗粒难以释出,无水的保存条件也使微生物难以生长。蛋白药物构象易变,难以耐受常用的蒸汽或干热灭菌,因此针对这一难题,本研究设计并探讨了采用较低温度下环氧乙烷熏蒸法对蛋白药微针贴片灭菌的可行性。赖脯胰岛素微针贴片在温度50℃、压力-30.3 kPa,相对湿度57.5%的条件下灭菌2 h,通过检测灭菌前后微针贴片中的赖脯胰岛素含量,并将灭菌后的微针贴片接种于培养基中观察14 d以验证灭菌效果。结果显示灭菌前后微针中的赖脯胰岛素含量无明显差别,符合含量均匀度要求,且培养基中无菌长出,初步建立了微针透皮贴片的灭菌方法。Microneedle transdermal patches represent the most promising dosage form for efficient and accurate non-injecting administration of biological medicine to date.Although microneedles only penetrate the epidermis and release drugs at the dermis layer without invading the body and causing skin injury,it is still regarded as injections in administrative approval.Developing a feasible sterilization method is therefore of great importance.Phase transition microneedle is formed of mixed hydrophilic polymers with polyvinyl alcohol (PVA)as the majority.After insertion into skin,the patch would absorb body fluid and convert to swollen hydrogel state enabling pre-loaded drug to be released from matrix of microneedles.Since bacteria and viral particles are several orders of magnitude larger than proteins in diameter and cannot be released from the network of the swollen matrix of microneedles,sterilization could be achieved more easily.To address the inability of sterilizing protein drugs by steaming and heating,the present study was aimed to investigate the feasibility of incubating microneedle patches in ethylene oxide atmosphere at relative mild temperature.The insulin lispro microneedle patches were treated in an ethylene oxide vapor of-30.3kPa at 50°C,with relative humidity of 57.5%,for 2h,followed by measurement of insulin lispro content changes by HPLC.There was no significant difference between sterile microneedles and non-sterile microneedles,meaning ethylene oxide would not have influence on drug content in microneedles.The treated microneedle patches were inoculated to culture medium for 14d to examine the efficiency of the sterilization,and found no bacterium growth,suggesting the feasibility of the ethylene oxide steaming sterilization.

关 键 词：微针 贴片 灭菌 环氧乙烷 赖脯胰岛素 

分 类 号：R944.9[医药卫生—药剂学]