盐酸利舒地尔/酒石酸溴莫尼定(Ripasudil Hydrochloride Hydrate/Brimonidine Tartrate) - 药物靶点：ROCK1 x α2A-AR_在研适应症：青光眼_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Ripasudil hydrochloride hydrate/brimonidine tartrate(Kowa)、K-232、Gla‐Alpha

+ [1]

靶点

ROCK1 x α2A-AR

作用机制

ROCK1抑制剂(Rho相关蛋白激酶-1抑制剂)、α2A-AR激动剂(肾上腺素能受体α-2a激动剂)

治疗领域

眼部疾病

在研适应症

青光眼

非在研适应症-

原研机构

Kowa Co., Ltd.

在研机构

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 (2022-09-26),

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

5

项与盐酸利舒地尔/酒石酸溴莫尼定相关的临床试验

JPRN-JapicCTI-205316 / Completed临床3期

K-232 clinical pharmacology study in healthy adult males

开始日期2020-06-13

申办/合作机构

Kowa Co., Ltd.

JPRN-jRCT2080225220 / Completed临床3期

K-232 clinical pharmacology study in healthy adult males

开始日期2020-06-13

申办/合作机构

Kowa Co., Ltd.

JPRN-jRCT2080225064 / Completed临床3期

K-232 phase 3 comparative study compared to brimonidine ophthalmic solution in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OH)

开始日期2020-03-02

申办/合作机构

Kowa Co., Ltd.

100 项与盐酸利舒地尔/酒石酸溴莫尼定相关的临床结果

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100 项与盐酸利舒地尔/酒石酸溴莫尼定相关的转化医学

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100 项与盐酸利舒地尔/酒石酸溴莫尼定相关的专利（医药）

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5

项与盐酸利舒地尔/酒石酸溴莫尼定相关的文献（医药）

2023-08-01·Advances in therapy

Crossover Randomized Study of Pharmacologic Effects of Ripasudil-Brimonidine Fixed-Dose Combination Versus Ripasudil or Brimonidine.

Article

作者: Tanihara, Hidenobu ; Koizumi, Noriko ; Isobe, Tomoyuki ; Aihara, Makoto ; Kojima, Satoshi ; Suganami, Hideki ; Minami, Hiroomi ; Kanazawa, Mizuho ; Yamamoto, Tetsuya

INTRODUCTION:

Multidrug regimens for glaucoma treatment often result in adherence issues due to inconvenience; these issues may be improved with fixed-dose combination drugs. The ophthalmic solution of ripasudil-brimonidine fixed-dose combination (RBFC; K-232) is the first treatment combining a Rho kinase inhibitor and an α₂-adrenoceptor agonist, and has demonstrated ability to lower intraocular pressure (IOP) and have various effects on conjunctival hyperemia and corneal endothelial cell morphology. This study evaluates the pharmacologic effects of RBFC treatment versus its separate components-ripasudil or brimonidine.

METHODS:

This single-center, prospective, randomized, open-label, blinded endpoint study with 3 × 3 crossover design randomly assigned healthy adult men to three groups (1:1:1) to undergo consecutive 8-day administration phases (with drug-free intervals of at least 5 days). Subjects received twice-daily instillation of RBFC → ripasudil → brimonidine (group A), ripasudil → brimonidine → RBFC (group B), or brimonidine → RBFC → ripasudil (group C). Endpoints included change in IOP, severity of conjunctival hyperemia, corneal endothelial cell morphology, pupil diameter, and pharmacokinetics.

RESULTS:

Eighteen subjects were assigned in total (six to each group). RBFC significantly reduced IOP from baseline at 1 h post-instillation on days 1 and 8 (12.7 vs. 9.1 and 9.0 mmHg, respectively; both P < 0.001), and provided significantly greater IOP reductions than ripasudil or brimonidine at several time points. The most common adverse drug reaction with all three treatments was mild conjunctival hyperemia, which transiently increased in severity with RBFC or ripasudil, peaking at 15 min post-instillation. In post hoc analyses, conjunctival hyperemia scores were lower with RBFC than with ripasudil at several time points. Transient morphologic changes in corneal endothelial cells occurred for up to several hours with RBFC or ripasudil, but not with brimonidine. Pupil diameter did not change with RBFC.

CONCLUSION:

RBFC significantly reduced IOP compared with each agent alone. A combination of each agent's pharmacologic profile was observed in that of RBFC.

TRIAL REGISTRATION:

Japan Registry of Clinical Trials; Registration No. jRCT2080225220.

2023-04-01·American journal of ophthalmology

Ripasudil–Brimonidine Fixed-Dose Combination vs Ripasudil or Brimonidine: Two Phase 3 Randomized Clinical Trials

Article

作者: Tanihara, Hidenobu ; Nojima, Toshiaki ; Aihara, Makoto ; Kawakita, Koji ; Suganami, Hideki ; Kojima, Satoshi ; Kanazawa, Mizuho ; Yamamoto, Tetsuya

PURPOSE:

To confirm the superiority of the intraocular pressure (IOP)-lowering effect of the ripasudil-brimonidine fixed-dose combination (RBFC, K-232) to ripasudil 0.4% or brimonidine 0.1% ophthalmic solution.

DESIGN:

Two prospective multicenter, randomized, double- or single-masked, active-controlled, phase 3 trials.

METHODS:

Patients with primary open-angle glaucoma or ocular hypertension whose IOP level was ≥18 mm Hg during treatment with ripasudil or brimonidine alone were randomized to 2 groups (RBFC and ripasudil) in a 1:1 ratio in the ripasudil-controlled trial and to 3 groups (RBFC, brimonidine, and ripasudil-brimonidine combination) in a 2:2:1 ratio in the brimonidine-controlled trial. The allocated study drugs were instilled twice daily for 8 weeks. The primary efficacy endpoint was the change in IOP 2 hours after instillation (11 AM) from the baseline to weeks 4, 6, and 8.

RESULTS:

There were 206 patients randomized in the ripasudil-controlled trial. Changes in IOP were -2.6 and -1.2 mm Hg in the RBFC and ripasudil groups, respectively, with a difference of -1.4 mm Hg (95% CI = -1.8 to -1.0 mm Hg; P < .001). There were 282 randomized patients in the brimonidine-controlled trial. Changes in IOP were -3.4 and -1.5 mm Hg in the RBFC and brimonidine groups, respectively, with a difference of -1.8 mm Hg (95% CI = -2.3 to -1.4 mm Hg; P < .001). The most frequent adverse event was conjunctival hyperemia.

CONCLUSIONS:

The IOP-lowering effect of RBFC was superior to that of ripasudil or brimonidine.

2008-08-01·Journal of applied microbiology3区 · 生物学

Isolation and partial characterization of a bacteriocin produced byPediococcus pentosaceusK23-2 isolated from Kimchi

3区 · 生物学

Article

作者: S.K. Han ; M.S. Shin ; K.S. Kim ; J.S. Ryu ; W.K. Lee

AIMS:

Screening and partial characterization of a bacteriocin produced by Pediococcus pentosaceus K23-2 isolated from Kimchi, a traditional Korean fermented vegetable.

METHODS AND RESULTS:

A total of 1000 lactic acid bacteria were isolated from various Kimchi samples and screened for the production of bacteriocin. Pediocin K23-2, a bacteriocin produced by the Pediococcus pentosaceus K23-2 strain, showed strong inhibitory activity against Listeria monocytogenes. The bacteriocin activity remained unchanged after 15 min of heat treatment at 121 degrees C or exposure to organic solvents; however, it diminished after treatment with proteolytic enzymes. The bacteriocin was maximally produced at 37 degrees C, when the pH of the culture broth was maintained at 5.0 during the fermentation, although the optimum pH for growth was 7.0. The molecular weight of the bacteriocin was about 5 kDa according to a tricine SDS-PAGE analysis.

CONCLUSIONS:

Pediococcus pentosaceus K23-2 isolated from Kimchi produces a bacteriocin, which shares similar characteristics to the Class IIa bacteriocins. The bacteriocin is heat stable and shows wide antimicrobial activity against Gram-positive bacteria, especially L. monocytogenes.

SIGNIFICANCE AND IMPACT OF THE STUDY:

Pediocin K23-2 and pediocin K23-2-producing P. pentosaceus K23-2 could potentially be used in the food and feed industries as natural biopreservatives, and for probiotic application to humans or livestock.

100 项与盐酸利舒地尔/酒石酸溴莫尼定相关的药物交易

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