摘要
肽类药物因其高特异性、高效性及低毒性的特点,对多种疾病的治疗具有显著优势。目前已有80余种肽类药物进入市场, 2019年全球销售额超500亿美元。然而,肽类药物通常分子质量较大、亲水性较强,消化道稳定性差,加之诸多生理屏障,导致其口服生物利用度极低,大多只能通过注射给药。但相较于患者依从性强的口服制剂,注射剂使用不便,注射后易出现不良反应,故而近年大量研究集中于提高肽类药物的口服生物利用度,部分递送技术如Eligen、Axcess等已成功应用于治疗性肽的口服制剂,并推动相关口服制剂实现上市及临床使用。本综述围绕肽类药物的口服递送,总结归纳近年来最新研究进展以及相关专利技术应用,促进口服肽类制剂的研发和临床转化。
Peptide drugs exhibit an irreplaceable role in clinics due to their high specificity, efficiency and low toxicity. At present, more than 80 peptide drugs have been approved for marketing with global sales exceeding $50 billion in 2019. However, with large molecular weights, high hydrophilicity and instability in digestive tract, oral peptide drugs encounter substantial physiological barriers leading to low oral bioavailability. Therefore, peptide drugs are mostly administered by parenteral routes. Although parenteral delivery of peptide drugs achieves high bioavailability, this is associated with inconvenience and discomfort, even causing severe side effects compared with the oral route possessing a high degree of patient compliance. Therefore, numerous studies concentrate on novel strategies to improve the oral bioavailability of peptide drugs. Some delivery technologies such as Eligenand Axcesshave been successfully applied to the oral dosage form of therapeutic peptides and have accelerated relevant oral formulations for Food and Drug Administration(FDA) approval and clinical treatment. In this review,we focus on the oral peptide delivery, mainly summarizing the progress of recent strategies used to overcome oral barriers and the commercialization applications of related patents, which could facilitate the research and development(R&D) of clinical applications of oral delivery techniques for peptide drugs.
作者
李琪
陈宏达
周天华
刘祥瑞
LI Qi;CHEN Hong-da;ZHOU Tian-hua;LIU Xiang-rui(School of Basic Medical Sciences,Zhejiang University,Hangzhou 310058,China)
出处
《药学学报》
CAS
CSCD
北大核心
2022年第7期2012-2023,共12页
Acta Pharmaceutica Sinica
基金
中国营养学会-中食营科低聚肽营养研究基金资助项目(CNS-FF2019A22)。
关键词
肽类药物
口服制剂
胃肠道吸收
渗透增强剂
专利药物
药物递送系统
peptide drug
oral drug administration
gastrointestinal absorption
permeation enhancer
patent medicine
drug delivery system
作者简介
通讯作者: 刘祥瑞,Tel:15967155397,E-mail:xiangrui@zju.edu.cn。
