前药技术在肺部吸入药物研发中的应用  

The application of prodrug technology in inhaled medicines

作　　者：陈韡亚 杨飞飞[1] 廖永红[1,2,3] CHEN Wei-ya;YANG Fei-fei;LIAO Yong-hong(Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100193,China;Jiangsu Kanion Parmaceutical Co.,Ltd.,Lianyungang 222001,China;State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process,Lianyungang 222001,China)

机构地区：[1]中国医学科学院、北京协和医学院药用植物研究所,北京100193 [2]江苏康缘药业股份有限公司,江苏连云港222001 [3]中药制药过程新技术国家重点实验室,江苏连云港222001

出　　处：《药学学报》2021年第10期2597-2611,共15页Acta Pharmaceutica Sinica

基　　金：中药制药过程新技术国家重点实验室开放基金资助项目(SKL2020M0201)。

摘　　要：与口服或注射等全身性给药相比,吸入药物直接递送至呼吸道发挥治疗作用,在呼吸系统疾病治疗方面具有明显优势。但现有吸入药物难以满足临床用药需求,且由于缺乏系统的理论和实践经验指导,新型吸入药物的研发面临巨大挑战。通过前体药物技术,针对候选药物的缺陷进行个性化修饰以满足吸入治疗要求,是目前可选择的吸入药物开发途径。本文对近20年来前药技术在吸入递送中的应用进行了综述。这些研究发现:酯化修饰或与大分子化合物偶联的前药技术可以延长药物肺部驻留;甘露糖修饰或酸敏感键连接可以实现肺泡巨噬细胞内释药;个性化修饰的前药可以获得适于吸入递送的理化性质,降低药物毒性。总体而言,前药技术的应用可以满足吸入药物开发的不同需求,为新型吸入药物的研发提供思路。Compared with systemic administration such as oral delivery or injection,inhaled medicines directly locate in the respiratory tract to exert therapeutic effects,offering obvious advantages in the treatment of respiratory diseases.Marketed inhaled medicines are yet difficult to meet the clinical demands,and there are considerable challenges in the discovery and development of novel inhaled medicines due to the lack of experiences-and property-based rules for inhaled compounds.Personalized modification of candidate drugs through prodrug technology to meet the requirements of inhalation therapy is the current alternative approach for inhaled drug development.In this review,we intend to summary the applications of prodrug technology in the research of inhaled medicines over the past 20 years.These studies have shown that esterified prodrugs and macromolecule conjugates could effectively prolong lung retention;mannose modification or acid-sensitive bond connection can achieve targeted drug release in alveolar macrophages;personalized modified prodrugs can obtain suitable physicochemical properties for pulmonary delivery and reduce drug toxicity.In general,the application of prodrug technology can modify the physicochemical and biopharmaceutical properties of drugs and may promote the discovery and development of novel inhaled medicines.

关 键 词：前体药物 吸入治疗 药物设计 生物药剂学 药代动力学 

分 类 号：R943[医药卫生—药剂学]