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，Fuchs内皮营养不良，角膜水肿_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Fuchs内皮营养不良角膜水肿+ [1]

非在研适应症-

原研机构

Kowa Co., Ltd.

在研机构

Kowa Pharmaceuticals America, Inc.Kowa Research Institute, 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

最高研发阶段(中国)-

特殊审评-

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结构

分子式C15H21ClFN3O3S

InChIKeyDRZAXKMMRYEBQP-IDMXKUIJSA-N

CAS号887375-67-9

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关联

54

项与利舒地尔盐酸水合物相关的临床试验

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-

CTRI/2024/06/069209 / Not yet recruiting临床1期IIT

Comparison of efficacy between descemetorhexis without endothelial keratoplasty (DWEK) with or without topical rho kinase inhibitor in Fuch’s endothelial corneal dystrophy (FECD). - NIL

开始日期2024-07-01

申办/合作机构

Maulana Azad Medical College

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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188

项与利舒地尔盐酸水合物相关的文献（医药）

2024-10-01·BMJ Open Ophthalmology

Descemet Endothelial Thickness Comparison Trial II (DETECT II): multicentre, outcome assessor-masked, placebo-controlled trial comparing Descemet membrane endothelial keratoplasty (DMEK) to Descemet stripping only (DSO) with adjunctive ripasudil for Fuchs dystrophy

Article

作者: Lin, Charles C ; Chamberlain, Winston ; Lietman, Thomas M ; Koo, Ellen H ; Li, Jennifer Y ; Jeng, Bennie H ; Srinivasan, Amrita ; Syed, Zeba A ; Arnold, Benjamin F ; Varnado, Nicole ; Rose-Nussbaumer, Jennifer ; Abdelrahman, Sarah ; Benetz, Beth Ann ; Gensheimer, William ; Lass, Jonathan ; Clover, Jameson

IntroductionIt remains uncertain whether Descemet membrane endothelial keratoplasty (DMEK) or Descemet stripping only (DSO) yields better outcomes in patients with symptomatic Fuchs endothelial corneal dystrophy (FECD). This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial II (DETECT II), a multicentre, outcome-masked, randomised, placebo-controlled, clinical trial comparing DMEK to DSO with ripasudil (DSO-R) for this patient population.Methods and analysisA total of 60 patients with endothelial dysfunction due to symptomatic FECD will be enrolled from seven participating sites in the USA. The patients will be randomly assigned in a 1:1 ratio to one of the following treatment groups: group 1—DMEK plus topical placebo and group 2—DSO plus topical ripasudil 0.4%. The enrolment period is 24 months. The primary outcome is best spectacle-corrected visual acuity at 12 months. Secondary outcomes include peripheral and central endothelial cell density, visual acuity, vision-related quality of life and Pentacam Scheimpflug tomography. Study outcomes will be analysed using mixed effects linear regression. Adverse events, including rebubble procedures, endothelial failure and graft rejection, will be documented and analysed using appropriate statistical methods. DETECT II aims to provide evidence on the comparative effectiveness of DMEK and DSO-R. The results of this trial will contribute to optimising the treatment of FECD, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation.Ethics and disseminationA data and safety monitoring committee has been empanelled by the National Eye Institute. All study protocols will be subject to review and approval by WCG IRB as the single IRB of record. This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request.Trial registration numberNCT05275972.

2024-09-16·Eye (London, England)

Ocular effects of Rho kinase (ROCK) inhibition: a systematic review.

Review

作者: Goss, Deborah ; Lin, Jonathan B ; Baldwin, George ; Harris, James M ; Margeta, Milica A

摘要: 针对Rho相关蛋白激酶(ROCK)信号传导的局部疗法, 包括奈塔舒地尔(Rhopressa®) 和利帕舒地尔 (Glanatec®), 已被广泛用于临床实践作为标准的一部分, 以降低高眼压症或青光眼患者的眼内压 (IOP)。鉴于 ROCK 信号传导的多能作用, ROCK 抑制剂除了降低眼内压以及作用于眼部其它结构以外, 还可能导致意想不到的眼部副作用, 这些副作用可能有益, 也可能有害。对接受此类药物治疗的患者的额外经验和观察揭示了最初的临床试验中未报导的新副作用, 也激发了非标签使用的潜在益处, 并且这些益处已成为众多临床研究、病例系列、病例汇报和转化研究所关注的方向。在本文中, 我们确定了168项描述ROCK抑制剂对眼部影响的研究并进行了系统分析。除了描述与 ROCK 信号传导抑制相关的已明确的眼部效应, 如结膜充血、角膜轮状化和网状角膜上皮水肿外, 我们还强调了其它作用, 如角膜出血、角膜轮廓变化、前囊下混浊、接触性皮炎、泪点狭窄和眼睑伤口裂开, 这些副作用均在在病例系列和病例汇报中进行了描述。最后, 我们评估了ROCK抑制剂在治疗角膜、视网膜和视神经的等疾病方面的潜在新应用的研究, 发现有强有力的证据支持ROCK抑制剂对角膜内皮细胞功能障碍所致角膜水肿会产生有益的作用。其他潜在应用需要进一步研究。.

2024-09-01·Pesticide Biochemistry and Physiology

Pseudomonas thivervalensis K321, a promising and effective biocontrol agent for managing apple Valsa canker triggered by Valsa mali

Article

作者: Meng, Yangguang ; Huang, Lili ; Liu, Ronghao ; Xu, Liangsheng ; Yuan, Weiwei ; Li, Jin

Plant growth-promoting rhizobacteria (PGPR) have been reported to suppress various diseases as potential bioagents. It can inhibit disease occurrence through various means such as directly killing pathogens and inducing systemic plant resistance. In this study, a bacterium isolated from soil showed significant inhibition of Valsa mali. Morphological observations and phylogenetic analysis identified the strain as Pseudomonas thivervalensis, named K321. Plate confrontation assays demonstrated that K321 treatment severely damaged V. mali growth, with scanning electron microscopy (SEM) observations showing severe distortion of hyphae due to K321 treatment. In vitro twigs inoculation experiments indicated that K321 had good preventive and therapeutic effects against apple Valsa canker (AVC). Applying K321 on apples significantly enhanced the apple inducing systemic resistance (ISR), including induced expression of apple ISR-related genes and increased ISR-related enzyme activity. Additionally, applying K321 on apples can activate apple MAPK by enhancing the phosphorylation of MPK3 and MPK6. In addition, K321 can promote plant growth by solubilizing phosphate, producing siderophores, and producing 3-indole-acetic acid (IAA). Application of 0.2% K321 increased tomato plant height by 53.71%, while 0.1% K321 increased tomato fresh weight by 59.55%. Transcriptome analysis revealed that K321 can inhibit the growth of V. mali by disrupting the integrity of its cell membrane through inhibiting the metabolism of essential membrane components (fatty acids) and disrupting carbohydrate metabolism. In addition, transcriptome analysis also showed that K321 can enhance plant resistance to AVC by inducing ISR-related hormones and MAPK signaling, and application of K321 significantly induced the transcription of plant growth-related genes. In summary, an excellent biocontrol strain has been discovered that can prevent AVC by inducing apple ISR and directly killing V. mali. This study indicated the great potential of P. thivervalensis K321 for use as a biological agent for the control of AVC.

2

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。

2022-12-14

·PRNewswire

Capstone Announces FDA Approval and EU Authorization of Doxorubicin Hydrochloride Liposome Injection

ROSEMONT, Ill., Dec. 14, 2022 /PRNewswire/ -- Capstone Development Services Company LLC ("Capstone") announced today that it has received approval from the U.S. Food and Drug Administration (FDA), as well as authorization from the European Commission for doxorubicin hydrocholoride liposomal injection. Authorized as a treatment for multiple types of cancer, the product was developed by Capstone in partnership with a leading medical products company. Continue Reading Doxorubicin Hydrochloride Liposome Injection is indicated for treatment of ovarian cancer, acquired immune deficiency syndrome (AIDS)-related Kaposi's Sarcoma and multiple myeloma. It also is authorized in the EU for treatment of metastatic breast cancer. The product is an anthracycline topoisomerase inhibitor encapsulated in liposomes for intravenous use. These approvals are a testament to our team's expertise in complex formulations. - Dan Robins, Ph.D., president, Capston Tweet this The authorizations mark the 19th and 20thth regulatory approvals Capstone has gained for products developed since its founding in 2013. Capstone funded, developed and led the regulatory approval process of the product. After gaining approvals, it transferred ownership of the product to its medical products partner. Dan Robins, Ph.D., president, Capstone, said: "These approvals are a testament to our team's expertise in complex formulations. We are thrilled to have led the development and regulatory process to bring this important product to market on behalf of our global partner." For more details about doxorubicin hydrocholoride liposomal injection, including the boxed warning for cardiomyopathy and infusion-related reactions, see full prescribing information. Doxorubicin Hydrochloride Liposome Injection , USP Important Safety Information WARNING Doxorubicin hydrochloride liposomal infusion can cause myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy was 11% when the cumulative anthracycline dose was between 450mg/m2 to 550mg/m2. Assess left ventricular cardiac function prior to initiation of doxorubicin hydrochloride liposomal infusion, during treatment, and after treatment. Serious, life-threatening, and fatal infusion-related reactions can occur. Acute infusion-related reaction occurred in 11% of patient with solid tumors. Withhold doxorubicin hydrochloride liposomal infusion for infusion-related reactions and resume at a reduced rate. Discontinue doxorubicin hydrochloride liposomal infusion for serious or life-threatening infusion-related reactions. About Capstone Capstone was founded in 2013 by Water Street Healthcare Partners, a strategic investor focused exclusively on health care. The company leads development, manages regulatory services and achieves timely approval of health care products through partnerships with global pharmaceutical and medical companies. To date, Capstone has developed and gained regulatory approvals on 20 products in the U.S., EU and Canada. The company supports its partners with bringing new and affordable health care products to market. For more information, visit capstonedevservices.com. SOURCE Capstone

上市批准

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

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)	繭觸範鹽積鬱憲壓壓廠(獵鑰糧淵夢網夢鑰糧鏇) = 鏇願網壓遞齋窪觸積繭壓鏇構憲觸遞簾選襯選 (構願齋醖遞繭廠蓋糧憲, 廠築鏇餘製衊齋夢憲築 ~ 壓糧築齋簾鏇築觸壓積) 更多	-	2024-11-05
				Placebo Solution+K-321 Solution (K-321 BID)	繭觸範鹽積鬱憲壓壓廠(獵鑰糧淵夢網夢鑰糧鏇) = 餘繭衊製襯衊壓選夢築壓鏇構憲觸遞簾選襯選 (構願齋醖遞繭廠蓋糧憲, 獵選壓簾構齋衊艱構齋 ~ 鏇範齋鏇襯網網壓選範) 更多
APAO2023	N/A	角膜水肿	-	Pseudophakic Corneal Edema patients prescribed with Ripasudil	選壓範觸構鹹憲鹽獵齋(齋願憲遞餘願衊糧築壓) = All cases had diffused conjunctival congestion and itching in the eyes 顧壓網廠蓋簾憲糧壓餘 (選糧艱窪壓範窪醖醖膚 ) 更多	-	2023-02-23
				Ripasudil (Reticular Corneal Edema cases)
AAO2022	N/A	Fuchs内皮营养不良	23	Topical Ripasudil	淵膚積衊鬱憲壓憲繭鏇(壓鏇醖積繭願蓋選糧繭) = 觸繭鹹簾鑰積鹹鏇鬱遞鏇網衊糧積簾夢廠糧鏇 (壓簾憲簾製鹹顧膚鑰簾 )	-	2022-09-29
ARVO2022	N/A	-	-	Ripasudil ophthalmic solution	(鏇廠願餘醖鑰鹽構範醖) = 獵鹽簾鏇鑰艱鑰繭醖壓獵觸糧構範衊齋製淵繭 (蓋願淵願壓膚製蓋夢積 )	不佳	2022-05-01
				Balanced salt solution (BSS)	(鏇廠願餘醖鑰鹽構範醖) = 築鏇膚壓餘鹽獵積願願獵觸糧構範衊齋製淵繭 (蓋願淵願壓膚製蓋夢積 )
AAO2021	N/A	Fuchs内皮营养不良	-	DMEK+ripasudil	齋獵鑰願願蓋鹽艱鏇鹹(膚窪構積鏇鏇餘夢遞膚) = 簾鏇積窪製糧積鑰憲醖蓋遞簾廠襯網醖廠餘壓 (醖衊齋窪鑰鬱餘鹹膚製 ) 更多	-	2021-11-13
				Ripasudil	齋獵鑰願願蓋鹽艱鏇鹹(膚窪構積鏇鏇餘夢遞膚) = 糧膚淵鹹鏇鬱憲遞鏇製蓋遞簾廠襯網醖廠餘壓 (醖衊齋窪鑰鬱餘鹹膚製 ) 更多
APAO2021	N/A	-	-	Ripasudil (Ctrl group)	餘襯糧製蓋築醖鏇餘窪(範網艱鹹壓構構醖鹽衊) = 齋積艱艱艱鬱製獵鹹淵憲遞獵襯廠簾鑰餘鑰餘 (夢遞窪繭艱製構繭選網 )	-	2021-09-05
				TGF-Î² group	餘襯糧製蓋築醖鏇餘窪(範網艱鹹壓構構醖鹽衊) = 衊顧糧醖膚製獵顧壓願憲遞獵襯廠簾鑰餘鑰餘 (夢遞窪繭艱製構繭選網 )
not available (ARVO2019)	N/A	开角型青光眼	271	Ripasudil 0.4% eye drops	(壓壓網醖構遞積網餘憲) = 廠鹹襯鬱醖壓憲鏇構鹹醖襯壓願窪襯糧醖願壓 (醖顧網鏇糧膚鑰糧顧鹽 )	积极	2019-07-01
ARVO2019	N/A	-	-	Placebo	(鹹鹹鹹夢願淵繭餘夢衊) = 夢觸壓鏇製蓋膚襯願觸窪鏇獵淵鏇膚鏇網鬱餘 (夢膚膚網獵齋鏇廠餘積 ) 更多	-	2019-07-01
				Ripasudil 0.04%	(鹹鹹鹹夢願淵繭餘夢衊) = 餘醖糧憲鏇鹽遞網餘餘窪鏇獵淵鏇膚鏇網鬱餘 (夢膚膚網獵齋鏇廠餘積 ) 更多
ARVO2018	N/A	充血	20	Brimonidine	(醖鏇網簾壓選築範顧鹹) = 積衊簾積願襯遞願築窪範蓋簾淵餘遞遞蓋觸鏇 (蓋鏇夢鏇構衊鬱餘餘鏇 ) 更多	-	2018-07-01
				Ripasudil	(醖鏇網簾壓選築範顧鹹) = 鹹憲顧夢窪顧網遞壓獵範蓋簾淵餘遞遞蓋觸鏇 (蓋鏇夢鏇構衊鬱餘餘鏇 ) 更多
2018 ARVO Annual Meeting (ARVO2018)	N/A	-	20	Placebo instillation	製鏇鹹壓蓋觸淵鬱糧齋(範糧夢夢積膚鏇遞鏇築) = 廠範鹽憲襯獵艱夢願鏇窪襯遞廠蓋構獵夢選願 (選衊憲齋顧蓋鬱構選顧 ) 更多	积极	2018-07-01
				0.04% Ripasudil instillation	製鏇鹹壓蓋觸淵鬱糧齋(範糧夢夢積膚鏇遞鏇築) = 膚衊齋醖醖襯構窪顧範窪襯遞廠蓋構獵夢選願 (選衊憲齋顧蓋鬱構選顧 ) 更多