Rho Kinase Inhibitor and Alpha-1 Blocker Combination for Glaucoma

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Solution Overview

Problem

Current treatments for glaucoma and ocular hypertension, particularly normal tension glaucoma, have limitations in potency and duration of ocular hypotensive effect, necessitating a more effective combination therapy.

Innovation Solution

Combining a Rho kinase inhibitor with an α1 blocker to enhance ocular hypotensive effects and prolong action, using specific compounds like (S)-(-)-1-(4-fluoro-5-isoquinolinesulfonyl)-2-methyl-1,4-homopiperazine and bunazosin, administered together to promote aqueous outflow and lower intraocular pressure.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing single drugs or conventional combinations are used for glaucoma treatment, then the treatment can be administered with standard therapies, but the ocular hypotensive effect is insufficient especially for normal tension glaucoma

Engineering Contradiction:
Improveocular hypotensive effectVSAvoideffectiveness across different glaucoma types
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines a Rho kinase inhibitor and an α1 blocker into a single ophthalmic composition that can be administered together. This merging of two different mechanisms of action (Rho kinase inhibition for trabecular outflow enhancement and α1 blockade for uveoscleral outflow promotion) creates a synergistic effect that achieves potent ocular hypotension in normal tension glaucoma and other glaucoma types where single agents are insufficient.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention creates a composite therapeutic agent by formulating both the Rho kinase inhibitor and α1 blocker in the same ophthalmic preparation. This composite approach allows simultaneous delivery of multiple active ingredients with complementary mechanisms, providing enhanced and sustained intraocular pressure reduction that adapts to various glaucoma pathologies including normal tension glaucoma.

Inventive Principle:
Principle #40Composite materials

2Duration of action of moving object

If existing treatments are used, then the administration process is simple, but the duration of ocular hypotensive action is short

Engineering Contradiction:
Improveduration of ocular hypotensive effectVSAvoidtreatment regimen complexity
Core Design Contradiction:
Duration of action of moving objectVSDevice complexity

Solution Approach 1:

By combining the Rho kinase inhibitor and α1 blocker into a single administered composition, the patent achieves prolonged ocular hypotensive duration through synergistic action while maintaining simple administration. The two agents work together to sustain intraocular pressure reduction longer than either agent alone, eliminating the need for complex multi-dose regimens or multiple separate administrations.

Inventive Principle:
Principle #5Merging (Combining)

3Reliability

If combination therapy with multiple drugs is used, then the ocular hypotensive potency is enhanced, but the treatment complexity increases

Engineering Contradiction:
Improveocular hypotensive potencyVSAvoidadministration convenience
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent merges multiple therapeutic agents (Rho kinase inhibitor and α1 blocker) into a single ophthalmic composition that can be administered as one unified treatment. This approach maintains the enhanced ocular hypotensive potency of combination therapy while simplifying administration to a single step, thereby improving ease of operation and patient compliance without sacrificing therapeutic effectiveness.

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentEP1902731B1Preventive or remedy for glaucoma
Publication Date: 2013.04.10 KOWA CO LTD
  • EP1902731B1 patent drawingFigure 1~2

AI summary

There is provided a preventive for glaucoma or a preventive or a remedy for ocular hypertension, with a potent ocular hypotensive effect and prolonged duration thereof. A preventive or a remedy for glaucoma comprising a Rho kinase inhibitor and an α1 blocker in combination.