利舒地尔盐酸水合物(Ripasudil Hydrochloride Hydrate) - 药物靶点：ROCK_在研适应症：青光眼，高眼压症，Fuchs内皮营养不良_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Ripasudil、Ripasudil hydrochloride hydrate (JAN)、Ripasudil hydrocholoride hydrate

+ [5]

靶点

ROCK

作用方式

抑制剂

作用机制

ROCK 抑制剂(Rho-相关激酶抑制剂)

治疗领域

眼部疾病遗传病与畸形其他疾病

在研适应症

青光眼高眼压症Fuchs内皮营养不良+ [2]

非在研适应症-

原研机构

Kowa Co., Ltd.

在研机构

Kowa Research Institute, Inc.

Kowa Pharmaceuticals America, Inc.

Kowa Co., Ltd.

非在研机构-

最高研发阶段批准上市

首次获批日期

日本 (2014-09-26),

青光眼高眼压症

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C15H21ClFN3O3S

InChIKeyDRZAXKMMRYEBQP-IDMXKUIJSA-N

CAS号887375-67-9

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关联

51

项与利舒地尔盐酸水合物相关的临床试验

NCT06048380

/ Recruiting临床3期IIT

The Effects of Ripasudil in Patients with Fuchs Endothelial Corneal Dystrophy Undergoing Femtosecond Laser Assisted Cataract Surgery

The purpose of this research is to investigate the effects of ripasudil administered as an ophthalmic solution in patients with FED after femtosecond laser assisted cataract surgery. The secondary aim is to identity the characteristics of patients who will benefit the most with the use of ripasudil based on the test results obtained from this study.

开始日期2025-03-01

申办/合作机构

Singapore Eye Research Institute

CTRI/2024/10/075399

/ Not yet recruitingN/AIIT

Role of Ripasudil in treatment of corneal edema following cataract surgery: A double blinded randomized controlled trial - NIL

开始日期2024-11-01

申办/合作机构

Jawaharlal Institute of Post Graduate Medical Education & Re

CTRI/2024/06/069429

/ Not yet recruiting临床4期IIT

A prospective comparative study to evaluate the effect of different Rho kinase inhibitors as a co adjuvant for endothelial cell survival in post Penetrating Keratoplasty patients

开始日期2024-07-02

申办/合作机构-

100 项与利舒地尔盐酸水合物相关的临床结果

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100 项与利舒地尔盐酸水合物相关的转化医学

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100 项与利舒地尔盐酸水合物相关的专利（医药）

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245

项与利舒地尔盐酸水合物相关的文献（医药）

2025-01-01·Journal of Ophthalmology

Effect of Ripasudil on the Change Rates of the Circumpapillary Retinal Nerve Fiber Layer Thickness in Patients With Primary Open‐Angle Glaucoma

Article

作者: Kameda, Takanori ; Sakurai, Katsumasa ; Suda, Kenji ; Hasegawa, Tomoko ; Akagi, Tadamichi ; Ikeda, Hanako Ohashi ; Tsujikawa, Akitaka ; Miyake, Masahiro

Purpose: The effect of the Rho‐kinase inhibitor ripasudil on the retinal optic nerve fiber layer (RNFL) remains unclear. We aimed to determine this effect in patients with primary open‐angle glaucoma (POAG) using optical coherence tomography (OCT) measurements and linear mixed analysis.Methods: This study prospectively included outpatients from a single center with POAG without a history of vitreoretinal or glaucoma surgery from December 2014 to June 2020, in whom the circumpapillary RNFL thickness (cpRNFLT) was measured more than three times before and after ripasudil initiation, without additional medication or surgery during the period. Measurements were performed using OCT in the follow‐up mode. The cpRNFLT change rates were compared before and after treatment using linear mixed models with adjustments for intraocular pressure (IOP) changes.Results: Thirty eyes of 20 patients (12 males and eight females) were included. Upon ripasudil prescription, the average cpRNFLT was 60.2 ± 2.1 μm. The average IOP was 15.1 ± 0.5 and 13.5 ± 0.5 mmHg, respectively, before and after treatment initiation, with a difference of −1.6 ± 0.3 mmHg. Analysis of 343 cpRNFLT measurements using linear mixed models revealed that the cpRNFLT change rate was −0.91 ± 0.15 and −0.40 ± 0.14 μm/year, respectively, before and after treatment onset, with an increase of 0.51 ± 0.21 μm/year. After adjusting for IOP changes, the improvement in cpRNFLT change rate was 0.33 ± 0.23 μm/year, albeit not statistically significant.Conclusion: The cpRNFLT change rate significantly increased after ripasudil administration, whereas the contribution of the IOP decline was not significant.

2024-12-01·Current Eye Research

Effects of Ripasudil Hydrochloride on Epithelial Repair in a Mouse Cornea

Article

作者: Saika, Shizuya ; Sumioka, Takayoshi ; Okada, Yuka ; Takada, Yukihisa ; Yasuda, Shingo ; Tamura, Tadahiko ; Yamanaka, Osamu

PURPOSEEffect of topical administration of a Rho kinase inhibitor, ripasudil, on epithelial wound healing in a mouse cornea was investigated. Effects of treatment of cultured human corneal epithelial cell (HCEC) line and organ-cultured corneal epithelium with ripasudil on expression of p-ERK was also examined.METHODSEpithelial defects with a diameter of 2.0 mm were prepared in the central corneas of C57BL/6 mice with or without 1-week travoprost pre-treatment, to which ripasudil or PBS as a control was instilled every 6 h immediately after preparation. The mice eyes were cultured with or without travoprost for 24-hrs. The expression levels of p-ERK in epithelium of mice eyes were compared by immunostaining after further 24-hrs culture with or without ripasudil for 24-hrs. HCEC were cultured with or without ripasudil and processed for examination for proliferation activity and protein expression of p-ERK by either immunostaining or Western blotting. The cells were also treated with or without travoprost for 24-hrs, and were further cultured with or without ripasudil. Expression levels of p-ERK were examined by Western blotting.RESULTSRipasudil treatment suppressed post-debridement epithelial healing in association with reduced proliferation activity in peripheral (limbal) epithelium in cornea with or without pre-treatment with travoprost. Ripasudil treatment accelerated p-ERK expression. Ripasudil supplementation upregulated proliferation with increased p-ERK in HCEC.CONCLUSIONRipasudil treatment promotes wound healing of the mouse corneal epithelium by enhancing cell proliferation on peripheral (limbal) epithelium.

2024-12-01·Canadian Journal of Ophthalmology

In vivo confocal microscopy findings after Descemet stripping only with and without topical ripasudil supplementation in Fuchs endothelial dystrophy

Article

作者: Moloney, Gregory ; Devasahayam, Raj N ; Oliver, Cameron ; Burgos-Blasco, Barbara ; Northey, Luke C ; Trinh, Tanya

OBJECTIVETo report corneal epithelial and corneal endothelial cell (CEC) changes following Descemet stripping only (DSO) with and without topical ripasudil using in vivo confocal microscopy (IVCM).METHODSProspective interventional case series of patients who underwent DSO for Fuchs endothelial dystrophy with or without postoperative topical ripasudil (4%, 6 times per day). Patients underwent IVCM (ConfoScan 3; NIDEK Technologies, Padova, Italy) at baseline, monthly until corneal clearance, and then every 6 months. En face images were obtained of the epithelium, anterior and posterior corneal stroma, and endothelium of the central and superior cornea. The epithelial and endothelial layer images were evaluated qualitatively.RESULTSIVCM imaging was obtained from 34 patients, 26 (76%) of whom were supplemented with ripasudil and 8 (24%) of whom were not. Two eyes (6%) did not clear and required a keratoplasty. IVCM confirmed epithelial and endothelial cell morphology changes and reestablishment of a CEC mosaic. Hyperreflective nuclei, pleomorphism, multinucleated cells, and pseudoguttae were identified within the descemetorhexis. In patients on ripasudil, epithelial cells demonstrated transition from stratified squamous to spindle cell shape in regions of ripasudil-induced honeycomb edema. Migrating cells adopted an amoeboid shape and cytoplasm elongation when crossing to central stroma. Transient epithelial cell morphology changes and endothelial cell amoeboid shape changes appear to be uniquely associated with ripasudil. Rarely, figures were noted in both ripasudil-treated and non-ripasudil-treated corneas that resembled mitotic bodies.CONCLUSIONSCECs display a range of adaptive mechanisms during healing to re-form the endothelial mosaic following DSO. Ripasudil administration appears to induce unique epithelial and endothelial cell changes.

1

项与利舒地尔盐酸水合物相关的新闻（医药）

2023-04-17

·生物谷

Molecular Therapy：海军军医大学李文林团队揭示ROCK抑制剂增强肝细胞移植的机制

该研究发现肝细胞分离导致细胞膜补体抑制分子的降解是诱导肝细胞移植后被机体快速清除的主要原因；发现抑制ROCK可维持肝细胞膜蛋白的完整性、阻断膜攻击复合体的组装、并显著提高肝细胞移植后的定植效率（图3）肝细胞移植作为原位肝移植的一种潜在的替代疗法，对于终末期肝病的治疗具有重要的研究意义，其优点包括：手术创伤小、操作简单、可进行多次移植等。然而，仍有一些障碍阻碍了肝细胞移植的临床应用。例如，大多数临床研究中使用的肝细胞通常来源于不适合器官移植的肝脏，肝细胞的来源和质量严重限制了肝细胞移植的应用。近年来，由多能干细胞分化或者通过谱系重编程来得到的肝细胞或肝祖细胞的研究取得了显著的进步，有望最终解决此问题。肝细胞移植的另一个主要限制是肝细胞的体内植入效率极低。在肝细胞移植后的24小时内超过70％的肝细胞因血液介导的即刻炎症反应（Instant blood-mediated inflammatory reaction，IBMIR）而被清除；存活的肝细胞还必须穿过肝窦内皮细胞屏障迁移至肝板，并与宿主肝细胞建立细胞连接后才能成功植入宿主肝脏，最终只有大约2%-6%的肝细胞可以成功定植到宿主肝脏。因此，提高肝细胞移植后在肝脏中的定植效率，是肝细胞移植应用于临床的迫切需要解决的问题。近日，海军军医大学李文林团队在 Molecular Therapy 期刊发表了题为：ROCK inhibition enhanced hepatocyte liver engraftment by retaining membrane CD59 and attenuating complement activation 的研究论文。该研究表明，肝细胞的分离导致细胞膜蛋白（包括补体抑制分子CD59）的大量降解，ROCK（Rho-associated coiled-coil containing kinases）抑制剂可以通过保留细胞膜CD59和阻断膜攻击复合物（membrane attack complex，MAC）的形成来保护移植的肝细胞、提高肝细胞的定植效率。在这项研究中，研究团队通过筛选发现ROCK抑制剂可显著增强肝细胞移植后在肝脏中的定植。体外补体活化实验表明ROCK抑制剂可以阻断膜攻击复合体（C5b-9）在肝细胞表面的组装（图1）。体内实验进一步证实了抑制ROCK可保护移植的肝细胞免受宿主补体系统的攻击。

100 项与利舒地尔盐酸水合物相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10463	利舒地尔盐酸水合物	S01EX	DB13165

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
青光眼	日本	Kowa Co., Ltd.	2014-09-26
高眼压症	日本	Kowa Co., Ltd.	2014-09-26

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
Fuchs内皮营养不良	临床3期	德国	Kowa Research Institute, Inc.	2023-03-30
Fuchs内皮营养不良	临床3期	美国	Kowa Research Institute, Inc.	2023-03-30
Fuchs内皮营养不良	临床3期	丹麦	Kowa Research Institute, Inc.	2023-03-30
Fuchs内皮营养不良	临床3期	加拿大	Kowa Research Institute, Inc.	2023-03-30
Fuchs内皮营养不良	临床3期	西班牙	Kowa Research Institute, Inc.	2023-03-30
Fuchs内皮营养不良	临床3期	英国	Kowa Research Institute, Inc.	2023-03-30
角膜水肿	临床3期	美国	Kowa Research Institute, Inc.	2022-08-04
角膜水肿	临床3期	波多黎各	Kowa Research Institute, Inc.	2022-08-04
眼科外科手术	临床3期	美国	Kowa Research Institute, Inc.	2022-08-04
眼科外科手术	临床3期	波多黎各	Kowa Research Institute, Inc.	2022-08-04

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04250207 (CTgov)	临床2期	Fuchs内皮营养不良	65	K-321 Solution (K-321 QID)	衊襯獵遞齋鹽糧範窪築(鏇範醖憲願衊蓋窪醖觸) = 製窪獵醖繭淵鬱憲醖餘選獵鏇鏇夢醖餘遞餘糧 (糧醖願選淵夢襯壓衊網, 壓窪鬱遞遞壓膚鬱糧憲 ~ 鬱製獵淵糧廠憲齋艱觸) 更多	-	2024-11-05
				Placebo Solution+K-321 Solution (K-321 BID)	衊襯獵遞齋鹽糧範窪築(鏇範醖憲願衊蓋窪醖觸) = 鑰顧窪觸憲衊觸齋構膚選獵鏇鏇夢醖餘遞餘糧 (糧醖願選淵夢襯壓衊網, 壓糧築醖壓積範網餘醖 ~ 蓋顧鏇遞繭餘齋醖網夢) 更多
APAO2023	N/A	角膜水肿	-	Pseudophakic Corneal Edema patients prescribed with Ripasudil	遞衊觸觸築範選繭顧鹹(鏇醖蓋簾繭夢衊築觸簾) = All cases had diffused conjunctival congestion and itching in the eyes 夢鏇製憲簾製淵餘鬱壓 (範襯觸獵範觸簾顧窪膚 ) 更多	-	2023-02-23
				Ripasudil (Reticular Corneal Edema cases)
AAO2022	N/A	Fuchs内皮营养不良	23	Topical Ripasudil	範簾獵壓膚夢網選構鹹(願鬱鑰鏇選網艱齋糧廠) = 壓選糧鹹獵蓋糧鹹願願膚網鏇簾齋夢製鏇獵遞 (製憲餘製淵網襯蓋醖範 )	-	2022-09-29
ARVO2022	N/A	-	-	Ripasudil ophthalmic solution	(艱艱獵襯糧範糧襯選築) = 餘淵鏇衊積鹽獵繭鏇窪選積積網選醖壓餘鏇觸 (構壓窪願蓋網襯壓網鹹 )	不佳	2022-05-01
				Balanced salt solution (BSS)	(艱艱獵襯糧範糧襯選築) = 襯網範遞齋製鏇鏇獵鏇選積積網選醖壓餘鏇觸 (構壓窪願蓋網襯壓網鹹 )
AAO2021	N/A	Fuchs内皮营养不良	-	DMEK+ripasudil	願醖網艱淵襯鑰鬱餘繭(築膚獵積顧鏇鏇膚網餘) = 範醖餘艱憲蓋製範積簾鹹範顧鹽憲構襯淵觸範 (鑰齋積獵蓋選蓋鏇鏇鏇 ) 更多	-	2021-11-13
				Ripasudil	願醖網艱淵襯鑰鬱餘繭(築膚獵積顧鏇鏇膚網餘) = 齋積夢選製鑰夢衊鹹築鹹範顧鹽憲構襯淵觸範 (鑰齋積獵蓋選蓋鏇鏇鏇 ) 更多
APAO2021	N/A	-	-	Ripasudil (Ctrl group)	衊窪構齋淵糧衊膚齋醖(糧選窪鬱範鏇範選衊構) = 餘壓襯蓋顧醖襯積鏇遞鏇淵鬱構蓋觸鹽製餘餘 (選獵繭遞鑰遞鹹襯網鹽 )	-	2021-09-05
				TGF-Î² group	衊窪構齋淵糧衊膚齋醖(糧選窪鬱範鏇範選衊構) = 築衊鬱鑰壓顧願築蓋醖鏇淵鬱構蓋觸鹽製餘餘 (選獵繭遞鑰遞鹹襯網鹽 )
ARVO2019	N/A	-	-	Placebo	(糧淵鏇鬱願蓋衊廠艱觸) = 糧餘獵齋網範糧襯鬱齋蓋積艱鬱鹹繭齋繭壓願 (襯願繭夢鏇積願糧觸構 ) 更多	-	2019-07-01
				Ripasudil 0.04%	(糧淵鏇鬱願蓋衊廠艱觸) = 願餘選願鹹鹹鹹願選獵蓋積艱鬱鹹繭齋繭壓願 (襯願繭夢鏇積願糧觸構 ) 更多
2018 ARVO Annual Meeting (ARVO2018)	N/A	-	20	Placebo instillation	憲築艱齋範獵鑰淵齋齋(鹹鑰獵構範遞膚築顧願) = 鏇顧鑰齋齋獵艱糧壓鹽衊簾鹹齋蓋顧衊觸廠簾 (艱襯鬱遞遞膚範糧夢窪 ) 更多	积极	2018-07-01
				0.04% Ripasudil instillation	憲築艱齋範獵鑰淵齋齋(鹹鑰獵構範遞膚築顧願) = 窪範鏇簾築鏇襯衊願積衊簾鹹齋蓋顧衊觸廠簾 (艱襯鬱遞遞膚範糧夢窪 ) 更多
2018 ARVO Annual Meeting (ARVO2018)	N/A	低眼压	9	Ripasudil 0.4% ophthalmic solution	(願遞醖衊壓願膚構鏇選) = 簾糧鹹蓋艱觸壓積夢壓築獵選淵製積觸襯鑰簾 (齋範網窪衊窪窪膚艱觸 )	不佳	2018-07-01
ARVO2018	N/A	充血	20	Brimonidine	(獵襯網膚願齋構獵繭餘) = 餘淵構觸憲艱淵艱簾艱遞壓膚膚壓遞淵選鏇顧 (襯築簾鏇淵憲衊網構網 ) 更多	-	2018-07-01
				Ripasudil	(獵襯網膚願齋構獵繭餘) = 衊艱鑰觸網糧製範積鹽遞壓膚膚壓遞淵選鏇顧 (襯築簾鏇淵憲衊網構網 ) 更多