Quinone-Based Nitric Oxide Donors for Glaucoma

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Solution Overview

Problem

Current treatments for glaucoma and ocular hypertension often come with significant side effects and develop nitrate tolerance, while existing nitric oxide donors have limitations in efficacy and tolerance issues, necessitating the development of more effective therapeutic agents.

Innovation Solution

The development of nitric oxide donor compounds of a specific formula that provide sustained activity with reduced tolerance and additional anti-inflammatory and antioxidant properties to regulate intraocular pressure and promote aqueous humor outflow.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stress or pressure

If conventional glaucoma drugs (beta-blockers, alpha-agonists, cholinergic agents, carbonic anhydrase inhibitors, prostaglandin analogs) are used to lower intraocular pressure, then intraocular pressure is reduced, but serious side effects occur

Engineering Contradiction:

Improveintraocular pressureVSAvoidside effects

Core Design Contradiction:

Stress or pressureVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical structure parameters by introducing a quinone moiety combined with nitrate or nitrite ester groups, creating compounds with improved pharmacological properties. This structural modification allows the drug to achieve therapeutic effects while reducing adverse reactions compared to conventional glaucoma medications.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention combines two functional moieties (quinone and nitrate/nitrite ester) into a single composite molecular structure. This composite approach integrates the benefits of both components: quinone provides antioxidant and anti-inflammatory activity, while the nitrate/nitrite ester provides nitric oxide donor capability for vasodilation and aqueous humor outflow enhancement.

Inventive Principle:

Principle #40Composite materials

2Stress or pressure

If nitric oxide donor compounds are used to treat glaucoma, then intraocular pressure is lowered, but nitrate tolerance develops reducing long-term efficacy

Engineering Contradiction:

Improveintraocular pressureVSAvoidduration of therapeutic effect

Core Design Contradiction:

Stress or pressureVSDuration of action of stationary object

Solution Approach 1:

The patent modifies the chemical parameters by combining nitrate/nitrite ester groups with quinone moieties, creating compounds that release nitric oxide more sustainably. This structural change alters the pharmacokinetic profile, reducing the development of tolerance and maintaining therapeutic efficacy over longer treatment periods.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The quinone-based nitric oxide donors provide continuous and sustained release of nitric oxide, ensuring prolonged therapeutic action. The molecular design enables sustained activity that prevents the tolerance development seen with conventional nitrate donors, maintaining effective intraocular pressure control over time.

Inventive Principle:

Principle #20Continuity of useful action

3Reliability

If existing nitric oxide donors are used, then some therapeutic effect is achieved, but efficacy is limited and tolerance issues occur

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidtolerance to treatment

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent creates composite molecules combining quinone and nitrate/nitrite ester moieties, producing compounds with enhanced and multifaceted therapeutic effects. This composite structure provides improved reliability through multiple mechanisms of action (nitric oxide donation, antioxidant activity, anti-inflammatory effects) while reducing adaptability issues like tolerance development.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The quinone-based nitric oxide donors exhibit multiple functions: they act as nitric oxide donors for vasodilation, antioxidants for oxidative stress reduction, and anti-inflammatory agents. This multi-functionality enhances therapeutic reliability for treating glaucoma while reducing the development of treatment tolerance through diverse pharmacological actions.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

These compounds effectively lower intraocular pressure with reduced tolerance issues, offering synergistic benefits in regulating aqueous humor outflow and providing antioxidant protection, thus addressing the limitations of existing treatments.

Implementation Method 1

nitric oxide donor compounds of formula (I) and their use in the treatment and/or prophylaxis of glaucoma and ocular hypertension

Methodology Applied

Scientific EffectNitric oxide donation:

Implementation Method 2

additional beneficial anti-inflammatory and antioxidant properties that work synergistically with the delivery of nitric oxide

Methodology Applied

Scientific EffectAntioxidant activity: Oxidation

Data Source

PatentEP2986288B1Quinone based nitric oxide donating compounds for ophthalmic use

Publication Date: 2017.04.12 NICOX SCI IRELAND

AI summary

The present invention relates to nitric oxide donor compounds having a quinone based structure of formula (I), wherein R1 to R6, n, m and p are as defined in claim 1, compositions thereof and said compounds for use in the treatment and/or prophylaxis of glaucoma and ocular hypertension.