胰岛素口服给药的困境与突破  

The dilemma and breakthrough of oral administration of insulin

作　　者：姚晟瑜 樊星砚 江宽 胡杨 魏刚[1,3,4] 甘勇 陆伟跃 YAO Sheng-yu;FAN Xing-yan;JIANG Kuan;HU Yang;WEI Gang;GAN Yong;LU Wei-yue(Key Laboratory of Smart Drug Delivery,Ministry of Education,School of Pharmacy,Fudan University,Shanghai 201203,China;Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;The Institutes of Integrative Medicine of Fudan University,Shanghai 200040,China;Shanghai Engineering Re-search Center of ImmunoTherapeutics,Shanghai 201203,China)

机构地区：[1]复旦大学药学院,教育部智能化递药重点实验室,上海201203 [2]中国科学院上海药物研究所,上海201203 [3]复旦大学中西医结合研究所,上海200040 [4]上海市免疫治疗工程研究中心,上海201203

出　　处：《药学学报》2020年第7期1549-1561,共13页Acta Pharmaceutica Sinica

基　　金：复旦大学-中国科学院上海药物研究所融合基金项目(FUSIMM 20173006);上海市中西医结合学科发展项目(20180101)。

摘　　要：糖尿病以高血糖为特征,源于胰岛素缺乏或抵抗,或两者兼有。胰岛素在糖尿病治疗中占据着不可替代的地位。皮下注射是胰岛素的主要给药途径,但患者依从性差,而且存在诸多不良反应。口服胰岛素更安全、更便捷,始终是人们探寻的"圣杯",但由于胰岛素自身的理化性质与体内的吸收屏障,很难达到理想的生物利用度。故本文综述了阻碍胰岛素口服给药的各种吸收屏障,以及近年来在创新药物制剂和生物材料驱动下,胰岛素口服给药领域开展的各种尝试和取得的研究进展。Diabetes is characterized by hyperglycemia,resulting from insulin deficiency or resistance,or both.Insulin plays an irreplaceable role in the treatment of diabetes.Subcutaneous injection is the main route of insulin administration,but usually leads to poor compliance and many side effects.Oral insulin is safer and more convenient,which has always been the Holy Grail for people to explore.After oral administration,insulin is absorbed into the hepatic portal vein and transported to the liver,which can activate the normal physiological functions and reduce the risk of hypoglycemia,insulin resistance,and improve patient compliance.However,the gastrointestinal tract has multiple absorption barriers such as chemical barrier,enzyme barrier,and permeation barrier.Due to the physical and chemical properties of insulin,it is difficult to achieve desired oral bioavailability.This article reviews the recent attempts and progress in the field of oral administration of insulin driven by innovative drug delivery technologies and biomaterials,including structural modification,enzyme inhibitors,absorption enhancers,various nanoparticles,liposomes,microspheres,and even microorganisms.Some clinical researches on oral insulin are also introduced.

关 键 词：糖尿病 胰岛素 口服给药 生物利用度 给药系统 肠道吸收 

分 类 号：R943[医药卫生—药剂学]