Ophthalmic Photo-Crosslinking with EDDS Enhancer
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Solution Overview
Problem
Current corneal crosslinking treatments are limited by rapid oxygen depletion, which restricts the rate and speed of crosslinking reactions, and can cause toxic side effects due to UV-A light exposure.
Innovation Solution
The introduction of a secondary amine enhancer, such as ethylenediamine-N,N'-disuccinic acid (EDDS), into an aqueous solution containing a photosensitizer like riboflavin sodium phosphate, increases the rate and efficiency of collagen crosslinking reactions, both in oxygenated and hypoxic conditions, thereby enhancing the treatment efficacy while reducing toxic side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If UV-A light is used to activate photosensitizer for corneal crosslinking, then crosslinking reaction is initiated, but oxygen depletion occurs rapidly limiting reaction rate and speed
Solution Approach 1:
The patent introduces a secondary amine compound as an intermediary substance that mediates between the photosensitizer and collagen. This amine compound donates electrons to the excited photosensitizer, enabling crosslinking reactions to proceed without direct oxygen involvement, thus resolving the oxygen depletion limitation while maintaining high reaction productivity
Solution Approach 2:
The patent changes the chemical parameters of the photosensitizing system by adding a secondary amine compound. This parameter change shifts the photochemical mechanism from an oxygen-dependent pathway to an amine-mediated pathway, allowing the crosslinking reaction to proceed at high rates independent of oxygen concentration
2Productivity
If UV-A light irradiation is applied to activate photosensitizer, then crosslinking reaction proceeds, but toxic side effects are caused
Solution Approach 1:
The patent converts the potentially harmful effect of UV-A light activation into a beneficial process by introducing a secondary amine compound that acts as an electron donor. This amine compound enables the photosensitizer to activate crosslinking reactions through a different mechanism that avoids the toxic side effects associated with direct UV-A activation, while maintaining high reaction speed
Solution Approach 2:
The secondary amine compound serves as a protective intermediary that allows UV-A activation to occur without direct harmful effects on the cornea. The amine compound absorbs and distributes the photoenergy, enabling crosslinking to proceed through a safer chemical pathway that eliminates toxic side effects while preserving productivity
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 use of EDDS as an enhancer significantly increases the rate and speed of collagen crosslinking, making the treatment more efficient and reducing the dependency on oxygen, thus improving surgical outcomes and minimizing toxic effects.
Implementation Method 1
When an electron of a photosensitising molecule with a singlet ground state is excited by absorption of UV radiation to a higher energy level
Implementation Method 2
The main photochemical reactions based on flavins as photosensitizer involve intramolecular and intermolecular photoreduction, photoaddition and photodealkylation
Implementation Method 3
the excited photosensitiser can collide with another molecule (quencher) to transfer energy in a second type of non-radiative process (quenching)
Implementation Method 4
The enhancer, in particular secondary amine, such as EDDS, added to a solution containing a photosensitizer... increases the rate and the kinetics of the photo-induced reductive radical generation
Data Source
Figure 1
AI summary
The present application relates to an aqueous solution comprising: at least one photosensitizer, at least one enhancer increasing the photosensitizing activity of a photosensitizer, and at least a viscous agent controlling the viscosity of the aqueous solution; wherein the at least one photosensitizer is contained in a concentration between 0.01 and 0.5% w/v, wherein the at least one enhancer is an electron donor and is contained in a concentration between 0.01 and 0.5% w/v, and wherein the aqueous solution has a viscosity of between 3 and 10,000 mPa s.