Tolbutamide KATP Inhibitor Glaucoma Aqueous Humor Flow
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for glaucoma either suppress aqueous humor production or increase outflow, but fail to adequately supply nutrients to the eye and eliminate harmful metabolic waste, leading to continued vision loss in patients.
Innovation Solution
A method involving the administration of a KATP channel inhibitor, such as tolbutamide, to patients with specific mutations in the KCNJ11 and AQP9 genes, which increases aqueous humor production and outflow, thereby addressing the nutrient supply and waste elimination issues in glaucoma patients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stress or pressure
If current drugs suppress aqueous formation to treat glaucoma, then intraocular pressure is reduced, but nutrient supply to the eye is reduced
Solution Approach 1:
The patent changes the therapeutic approach from suppressing aqueous humor production to stimulating it. By using compounds that activate the prostaglandin FP receptor or inhibit the KATP channel, the patent transforms the parameter of aqueous humor production from reduced to increased, thereby simultaneously achieving pressure reduction and improved nutrient supply through the increased fluid flow.
2Stress or pressure
If current drugs increase aqueous outflow to treat glaucoma, then intraocular pressure is reduced, but harmful metabolic waste is not adequately eliminated
Solution Approach 1:
The patent establishes continuous and enhanced aqueous humor flow that simultaneously performs multiple functions: maintaining pressure reduction and continuously transporting metabolic waste products away from the eye. The increased aqueous production and outflow create a continuous flushing action that eliminates waste accumulation while sustaining pressure control.
3Quantity of substance
If aqueous humor production is increased to supply nutrients, then eye health is improved, but intraocular pressure may increase
Solution Approach 1:
The patent merges two previously separate therapeutic goals into a single treatment mechanism: increasing aqueous humor production for nutrient supply and increasing outflow for pressure control are achieved simultaneously through the same pharmacological action. The compounds used both stimulate production and enhance drainage, combining multiple benefits in one therapeutic approach.
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
The method significantly increases aqueous humor production by up to 150% and outflow by 350%, effectively reducing intraocular pressure and improving eye health in glaucoma patients, while avoiding the side effects of existing treatments.
Implementation Method 1
administering a KATP channel inhibitor, such as tolbutamide, to patients with specific mutations in the KCNJ11 and AQP9 genes, which increases aqueous humor production and outflow
Implementation Method 2
determining if the rs1867380 ACA→GCA SNP is present in the aquaporin-9 (AQP9) gene, which replaces the amino acid threonine with alanine at position 279 (T279A) of AQP9
Data Source
AI summary
Provided herein are methods of treating glaucoma in a patient, comprising: obtaining a biological sample from the patient; testing the biological sample for presence of a mutation in Kir6.2 protein or KCNJ11 gene and a mutation in the Aquaporin-9 protein or AQP-9 gene; and provided that the biological sample tests positive for the presence of a mutation in Kir6.2 protein or KCNJ11 gene and a mutation in the AQP-9 gene or aquaporin-9 protein, administering to the patient a therapeutically effective amount of a sulfonylurea such as tolbutamide or a physiologically equivalent salt or solvate thereof and a pharmaceutically acceptable carrier. Also provided herein are methods of maintaining and/or improving eye health in a subject, comprising: administering to the patient a therapeutically effective amount of tolbutamide or a physiologically equivalent salt or solvate thereof, and a pharmaceutically acceptable carrier.