Timolol

引用本文 张 涛, 黄 聪, 刘会文, 等．近视防控用阿托品眼用制剂的研究进展[J]．中国医药工业杂志, 2024, 55(12): 1603-1611．DOI：10.16522/j.cnki.cjph.2024.12.001 Research Progress of Atropine Ophthalmic Formulations for Myopia Prevention and Control 近视防控用阿托品眼用制剂的研究进展 张 涛1,2，黄 聪2，刘会文2，陆伟跃1* (1. 复旦大学药学院，上海 201203；2. 拨康视云生物医药科技( 广州) 有限公司，广东广州 510663) 摘要 低浓度阿托品滴眼剂作为延缓青少年近视的眼用制剂，临床疗效已得到广泛认可，但已上市的硫酸阿托品水溶液型滴眼剂存在因pH 值低而导致的眼刺激性、制剂稳定性差和患者依从性差等问题。该文对目前在研和在售的硫酸阿托品眼用制剂的处方和制备工艺进行了文献调研和总结，分析了各种改善硫酸阿托品眼用制剂稳定性和依从性的技术方案特点和优劣势，以期为阿托品眼用制剂的优化提供一定的参考。 关键词 阿托品；近视；眼用制剂；滴眼剂；研究进展 文章节选 1 全球青少年近视防控的非手术方法概述 近视是全球性的公共健康问题。过去20 年，近视的发病率逐年增长，并且出现了低龄化趋势，亚洲地区近视儿童的增加尤为迅速。确切的近视发病机制尚不清楚，而目前的临床研究及流行病学调查结果提示，遗传、环境、学习压力以及对于电子产品的依赖等因素在近视发病及进展过程中起重要作用。 可用于防控青少年近视的非手术方法有如下几种。①行为干预：主要是增加户外活动和减少近距离用眼等，对预防近视的发生和减缓假性近视向近视的转换效果明显，可延缓近视进展。②框架眼镜：是矫正青少年近视的首选方式，可避免视疲劳，但普通框架眼镜不可控制近视程度的增长，对于高度近视以及散光、屈光参差近视患者的矫正效果并不理想，使用不当反而会使近视程度加深。③角膜塑形用硬性透气接触镜(orthokeratology lens，即OK 镜)：为Ⅲ类医疗器械，通过角膜塑形术进行视力矫正，可延缓青少年近视的发展，但个体差异使得配镜及护理费用较高，治疗效果还会随时间延长而减弱，且配戴过程存在适配不良、角膜上皮受损或感染的风险。另外，OK 镜佩戴者中，有色素环形成和角膜神经类型( 纤维线)改变等不良反应的报道。④多焦点软性角膜接触镜：验光、配镜比OK 镜简单，近视控制效果相似，但镜片设计差异较大，不同设计对镜片的偏位、矫正效果以及视功能恢复的影响不同，如果验配和使用不当，会引起眩光、光晕、视力模糊、视野扭曲、复视、头晕或微生物感染等并发症，影响佩戴者的生活质量和满意度。⑤口服药物：近视治疗药物的临床试验申请较少，目前有7-甲基黄嘌呤和核黄素等用于口服治疗近视的报道，但作用机制尚不明确。⑥滴眼剂：目前在研的控制近视程度增长的滴眼剂产品有阿托品、托吡卡胺、噻吗洛尔、哌仑西平和噻托溴铵滴眼剂等。其中， 低浓度阿托品滴眼剂的多项临床试验结果已证明，该药品可有效延缓青少年的近视。从2019 年开始，国家卫生健康委员会在《儿童青少年近视防控适宜技术指南》中明确，低浓度阿托品滴眼剂可有效延缓青少年近视进展。另外，低浓度阿托品滴眼剂也被欧洲眼科学会与国际近视合作机构、考克兰循证医学数据库推荐为效果仅次于行为干预、优于OK 镜和软性角膜接触镜的青少年近视控制方式。2024 年3 月5 日，沈阳兴齐眼药股份有限公司的0.01％硫酸阿托品滴眼液经NMPA批注上市。 扫描二维码阅读原文/登录官网查看 了解更多文章信息 作者简介 ：  张 涛(1983—)，男，博士研究生，专业方向 ：生物与医药。 通信作者 ：  陆伟跃(1960—)，男，教授，从事药物靶向策略及递药系统研究。 E-mail：wylu@shmu.edu.cn 关于转载：原创内容未经允许，不得转载 END 欢迎订阅 《中国医药工业杂志》 《中国医药工业杂志》是我国医药工业领域中办刊历史最长的医药期刊，是由上海医药工业研究院主管，上海医药工业研究院、中国药学会和中国化学制药工业协会主办的全国性综合医药学术刊物，国内外公开发行。自1970年11月创刊以来，《中国医药工业杂志》 始终以报道我国医药工业和科研中的成果和经验为宗旨，刊载了大量反映中国医药工业发展水平的论文和论著，积累了丰富的第一手原始资料；同时密切关注国际上制药技术的发展新动向，刊登有指导意义的综述和专论。期刊订阅详情请登录《中国医药工业杂志》官网（http://www.cjph.com.cn）了解。 《中国医药工业杂志》编辑部

MISSOULA, Mont.--( BUSINESS WIRE )--OSRX, Inc. today expressed its profound disappointment with the recent jury verdict in the case of ImprimisRx, LLC v. OSRX, Inc. The company believes the decision to be unjust and not based on the facts presented during the trial. Despite this setback, OSRX remains resolute in its commitment to challenge this outcome and address the significant issues that persist. “ Leading up to the trial, OSRX won summary judgment on ImprimisRx’s false advertising claims, and ImprimisRx abandoned its copyright claim,” said Dylan Liddiard of Wilson Sonsini Goodrich & Rosati, who defended OSRX. “ The Court did not enter final judgment based on the jury verdict, as there remain significant legal and equitable issues for the Court to decide, including laches, unclean hands, fraud on the USPTO, and the sufficiency of evidence regarding damages. We look forward to having an opportunity for the trial judge to decide these significant issues in December. This is far from over.” The case, brought by ImprimisRx, a wholly owned subsidiary of Harrow (Nasdaq: HROW), was tried in the United States District Court for the Southern District of California. The jury found OSRX, Inc. and its related party, Ocular Science, Inc., guilty of willful trademark infringement and unfair competition, awarding $34.9 million in damages. OSRX, Inc. contends that ImprimisRx relied on several false premises during the trial, some of which include: “Pred," "moxi," “dex” and "brom" are not generically used abbreviations within ophthalmology for prednisolone, moxifloxacin, dexamethasone and bromfenac and were not being used prior to ImprimisRx’ trademark filings. The trademarks “Dex-Moxi” and “Pred-Moxi” are not descriptive of the active ingredients in each medication. OSRX’s intermittent use of the abbreviations to accurately describe the ingredients in its own medications caused “significant confusion” among prescribers in the industry. 100 percent of OSRX’s sales were wrongfully gained through said confusion. ImprimisRx is entitled to 100 percent of all OSRX sales. OSRX is not entitled to “fair use” of these abbreviations to describe the ingredients in its medications. ImprimisRx was being truthful in its USPTO trademark applications when it said things like the abbreviation “TIM” could be mistaken by prescribers to mean “Traditional Indian Medicine” rather than Timolol, one of the most widely prescribed glaucoma medications in ophthalmology. OSRX was repeatedly asked to stop using the trademarks for many years, despite not a single cease-and-desist letter or email being produced to support that claim. OSRX, Inc. asserts that these claims are patently false and widely recognized as such within the industry, pointing to the fact that Imprimis was unable to produce or name a single prescriber lost due to “customer confusion” and had no documented evidence of said confusion. Furthermore, the jury was barred from hearing evidence related to ImprimisRx’s checkered safety and compliance record – ranging from FDA warning letters and product safety recalls to severe adverse events and even a patient fatality – as a feasible explanation for why it has lost market share to OSRX. In addition, the jury disregarded a genericism survey conducted by a leading national expert that found nearly 70% of ophthalmologists and optometrists who prescribe compounded medications believe all of the trademarks at issue, including pred-moxi-brom, to be generic terms, which are not protectable under U.S. trademark law. This has been OSRX's position on the matter for nearly a decade. " Sadly, this is nothing more than a billion-dollar Big Pharma company using anticompetitive tactics to try and choke out a much smaller competitor so they are free to drive up the costs of medication and monopolize the compounded ophthalmic space," said Anthony Sampietro, Founder and CEO of OSRX. " Rather than competing with us on the playing field and allowing for consumer choice, they opted to exploit the jury process. We will not be bullied or acquiesce to these unethical tactics because if we do, it's the thousands of OSRX prescribers and patients across the country who have to pay the price. I founded this company to put patients ahead of profits, and I will continue to stand my ground on that issue.” OSRX, Inc. is committed to defending its position and ensuring that its innovative contributions to the eyecare pharmaceutical market are recognized and protected. The company will explore all available legal avenues to overturn this verdict and continue its mission to provide high-quality, affordable eyecare solutions. Case No. 3:21-cv-01305-BAS-DDL . About OSRX: OSRX is an FDA-registered 503B outsourcing facility committed to transforming ophthalmic care through quality compounded solutions. The Missoula, MT-based company is on a mission to redefine the landscape of the corrective eye care market with a focus on simplicity, affordability and patient-centric care. Trusted by more than 5,500 prescribers across the U.S., OSRX is providing A New View of Medicine®. Learn more at www.osrxpharmaceuticals.com .