A novel fixed-combination timolol-netarsudillatanoprost ophthalmic solution for the treatment of glaucoma and ocular hypertension  

作　　者：Tao Wang Yunran Zhang Meiling Chi Chen Zhao Linlin Cao Chutong Tian K.Kamei Ying Zheng Qikun Jiang 

机构地区：[1]Department of Pharmaceutics,Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Changzhou pharmaceutical factory co.LTD,Jiangsu 213000,China [3]Department of Pharmaceutics,The Second Hospital of Dalian Medical University,Dalian 116023,China [4]State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macao,Macao,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2022年第6期938-948,共11页亚洲药物制剂科学（英文）

基　　金：financially supported by the Liao Ning Revitalization Talents Program(XLYC1902061)。

摘　　要：Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration,poor efficacy and side effects.Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic solution(FC-TNL)has the ability to treat glaucoma by lowering the intraocular pressure(IOP)with great efficacy and improving patient compliance.However,the commercialized netarsudil dimesylate precipitated when the p H of the solution was above 5.4,or when maleic acid,the salt of commercial timolol maleate,was mixed with netarsudil dimesylate.Consequently,the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in p H 4.8–5.2 solution by synthesizing timolol mesylate.Next,the morphology of timolol mesylate was observed by scanning electron microscopy,differential scanning calorimetry,thermogravimetric analysis,and powder X-ray diffraction.The prepared FC-TNL showed good stability during refrigeration storage.Additionally,FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study.Importantly,oncedaily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells.The FC-TNL was stable,safe and effective,being a promising glaucoma therapeutic.

关 键 词：GLAUCOMA Intraocular pressure Homologous salt engineering strategy Timolol mesylate Fixed-combination timolol-netarsudil-latanoprost ophthalmic solution 

分 类 号：R775[医药卫生—眼科]