Adenosine A1 Agonist Ophthalmic Composition for Glaucoma

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Solution Overview

Problem

Current glaucoma treatments, such as miotics, carbonic anhydrase inhibitors, and beta-blockers, often come with undesirable side effects, leading to decreased patient compliance and ineffective management of elevated intraocular pressure (IOP) in glaucoma and ocular hypertension.

Innovation Solution

The use of a selective adenosine A1 agonist, specifically ((2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl nitrate, administered topically as an ophthalmic pharmaceutical composition, to reduce IOP in humans with glaucoma or ocular hypertension.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing glaucoma treatments (miotics, carbonic anhydrase inhibitors, beta-blockers) are used to reduce intraocular pressure, then IOP reduction is achieved, but undesirable side effects occur leading to decreased patient compliance

Engineering Contradiction:
ImproveIOP reduction effectivenessVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by switching from conventional glaucoma treatment mechanisms to adenosine A1 receptor agonism. This represents a fundamental change in the pharmacological parameter (receptor target) while maintaining the therapeutic goal of IOP reduction, thereby achieving effectiveness while avoiding the side effects associated with traditional agents

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces adenosine A1 receptor agonists as an intermediary mechanism. Instead of directly affecting aqueous humor production or outflow through conventional pathways, the treatment uses adenosine receptor activation as an intermediate step to achieve IOP reduction, which provides a safer alternative with fewer side effects

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If existing glaucoma treatments are used to control IOP, then pressure reduction is achieved, but patient compliance decreases due to side effects

Engineering Contradiction:
ImproveIOP controlVSAvoidpatient compliance
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent changes the pharmacological parameter from conventional agents to adenosine A1 receptor agonists, which provides effective IOP control while having a more favorable side effect profile, thereby improving patient compliance without sacrificing therapeutic reliability

Inventive Principle:
Principle #35Parameter changes

3Reliability

If conventional glaucoma therapies are administered to reduce IOP, then therapeutic effect is achieved, but treatment safety decreases due to serious side effects

Engineering Contradiction:
Improvetherapeutic effectVSAvoidserious side effects
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses adenosine A1 receptor agonism as an intermediary mechanism that achieves IOP reduction through a different physiological pathway, avoiding the direct toxic effects on pulmonary tissue, ocular structures, and other systems associated with conventional therapies

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent extracts the essential therapeutic function (IOP reduction) from the harmful components of conventional treatments by selecting a different mechanism of action that achieves the same goal without the associated side effects

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentEP2424546B1Method of reducing intraocular pressure in humans
Publication Date: 2015.10.28 INOTECK PHARMA CORP
  • EP2424546B1 patent drawingFigure 1
  • EP2424546B1 patent drawingFigure 2a
  • EP2424546B1 patent drawingFigure 2b

AI summary

Provided herein are compounds of Formula I, compositions comprising an effective amount of a compound of Formula I, and methods for reducing intraocular pressure comprising administering an effective amount of compounds of Formula I to a subject in need thereof.