Primary Amine Compounds for Ocular Disorder Treatment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods fail to effectively address elevated levels of all-trans-retinal in ocular tissue, leading to retinal degeneration and associated disorders such as Stargardt disease and macular degeneration, as they either inhibit essential enzymes or cause night blindness.
Innovation Solution
Primary amine compounds that form a Schiff base with all-trans-retinal, reducing its toxicity without inhibiting RPE65 or LRAT enzymatic activity, thereby promoting 11-cis-retinal production and delivered through various administration methods including topical, systemic, and intravitreal routes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If retinylamine is used to inhibit RPE65 enzyme activity, then all-trans-retinal accumulation is reduced, but visual cycle function is compromised causing night blindness
Solution Approach 1:
The patent introduces primary amine compounds as intermediary agents that form reversible Schiff base adducts with all-trans-retinal. These compounds act as mediators that bind the toxic aldehyde without interfering with the natural retinoid cycle enzymes RPE65 and LRAT, thus reducing toxicity while preserving visual cycle function.
Solution Approach 2:
The patent converts the harmful all-trans-retinal aldehyde into a beneficial form by forming reversible Schiff base adducts with primary amine compounds. This transformation reduces the cytotoxic effects of all-trans-retinal while the adducts can be metabolized through alternative pathways, turning a harmful substance into a protective therapeutic agent.
2Use of energy by moving object
If visual pigments are densely packed to increase light absorption, then photoreceptor sensitivity is improved, but all-trans-retinal accumulation increases causing toxicity
Solution Approach 1:
Primary amine compounds serve as intermediary agents that selectively bind excess all-trans-retinal released from densely packed visual pigments. These compounds form reversible Schiff base adducts that prevent toxic accumulation while allowing the visual pigments to maintain their high-density packing for optimal light absorption.
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 reduce the formation of toxic by-products like A2E and retinal dimer, promote 11-cis-retinal production, and prevent retinal degeneration without causing night blindness, thus maintaining photoreceptor health and vision.
Implementation Method 1
Primary amine compounds that form a Schiff base with all-trans-retinal, reducing its toxicity
Data Source
AI summary
A method of treating an ocular disorder in a subject associated with increased all-trans-retinal in an ocular tissue includes administering to the subject a therapeutically effective amount of a primary amine compound of formula (I); and pharmaceutically acceptable salts thereof.