药物与眼黑色素结合的体内外研究方法及意义  

In vitro-in vivo Research Methods and Significance of Binding of Drugs with Melanin

作　　者：王若男 钱仪敏 阮斌 宋硕 李华 WANG Ruonan;QIAN Yimin;RUAN Bin;SONG Shuo;LI Hua(National Shanghai Center for New Drug Safety Evaluation&Research,China State Institute of Pharmaceutical Industry,Shanghai InnoStar Biotech Co.,Ltd.,Shanghai 201203)

机构地区：[1]中国医药工业研究总院国家上海新药安全评价研究中心,上海益诺思生物技术股份有限公司,上海201203

出　　处：《中国医药工业杂志》2020年第9期1099-1106,共8页Chinese Journal of Pharmaceuticals

基　　金：国家“重大新药创制”科技重大专项(2018ZX09201017-008)。

摘　　要：黑色素是在黑色素小体中合成的一类聚合物。研究显示碱性、亲脂性的芳香族化合物理论上都能够与黑色素发生结合,导致其在含有黑色素的组织中发生积聚,影响药物在体内的药动学和药效学,并可能导致潜在的毒性。然而,在药物递送领域中却也可以利用药物与黑色素的亲和性,增加眼底疾病治疗药物的靶向性。目前常用的药物-黑色素结合能力的研究方法包括体外、体内和计算机预测模型,但尚无基于清楚的结合机制的研究方法。本文对近年来有关药物-黑色素结合能力的体外和体内的研究方法进行详细阐述,并比较了二者的适用性和科学性,以期能够为眼科药物非临床研究提供有效的参考。Melanin is a kind of polymers synthesized in melanosomes.Studies have shown that basic and lipophilic aromatic compounds can theoretically bind with melanin,causing accumulation of drugs in tissues containing melanin,changing their local pharmacokinetic and pharmacodynamic profiles to introduce potential toxicity.However,in the field of drug delivery,the melanin binding can be used to increase the targeting of drugs for ocular fundus diseases.The current research methods for drugs binding with melanin include in vitro,in vivo,and in silico modeling,but there are no research methods based on mechanistic understanding of melanin binding with drugs.Herein the in vitro and in vivo research methods of melanin binding in recent years,the applicability and scientificity are summerized in order to provide effective references for non-clinical research of ophthalmic drugs.

关 键 词：黑色素 药物-黑色素结合 眼毒性 

分 类 号：R965[医药卫生—药理学] R914[医药卫生—药学]