Eye Pharmaceutical Formulation for UV-Free Collagen Cross-Linking
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Solution Overview
Problem
Current treatments for collagenic eye disorders, such as keratoconus, involve UV radiation that can cause damage to corneal endothelium and stromal cells, require delicate surgical techniques, and have pH stability issues, necessitating improved approaches for collagen cross-linking.
Innovation Solution
A pharmaceutical composition comprising an aqueous vehicle with a water-soluble cross-linker and a buffer to maintain pH between 6.0 to 8.5, which allows for collagen cross-linking without UV radiation, ensuring stability and safety for eye administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If UV radiation is used for corneal cross-linking, then collagen cross-linking is achieved, but damage to corneal endothelium and stromal cells occurs
Solution Approach 1:
The patent replaces the photochemical cross-linking mechanism (UV radiation + riboflavin) with a chemical cross-linking mechanism using water-soluble carbodiimide crosslinkers. This substitution eliminates the need for UV radiation while achieving effective collagen cross-linking, thereby resolving the contradiction between achieving cross-linking strength and avoiding cellular damage from UV exposure
Solution Approach 2:
The patent changes the chemical parameters of the cross-linking process by using carbodiimide-based crosslinkers (such as EDC or GS) that operate under physiological pH conditions without requiring UV activation. This parameter change allows cross-linking to proceed without the harmful UV radiation, maintaining collagen strength while protecting corneal cells
2Strength
If epithelium removal is performed to enhance riboflavin penetration, then cross-linking effectiveness is improved, but surgical complexity and infection risk increase
Solution Approach 1:
The patent substitutes the riboflavin-mediated photochemical cross-linking system with a direct chemical cross-linking system using water-soluble carbodiimides. This substitution allows the crosslinker to penetrate the intact epithelium and act on collagen without requiring epithelial removal, thereby simplifying the surgical procedure while maintaining cross-linking effectiveness
Solution Approach 2:
The patent uses water-soluble carbodiimide crosslinkers as intermediaries that can traverse the epithelial barrier and directly interact with collagen molecules. These crosslinkers serve as effective mediators that do not require epithelial removal for penetration, thus reducing surgical complexity and infection risk while achieving the desired cross-linking effect
3Strength
If disulfosuccinimidyl suberate is used for cross-linking, then collagen cross-linking is achieved, but pH stability deteriorates
Solution Approach 1:
The patent modifies the chemical structure of the carbodiimide crosslinker by adding water-soluble groups (such as sulfosuccinimidyl groups) to enhance aqueous solubility and improve pH stability. This structural parameter change allows the crosslinker to maintain stable pH levels in aqueous environments while effectively cross-linking collagen, resolving the contradiction between cross-linking capability and pH stability
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 composition effectively cross-links collagen, maintaining structural integrity of the eye, reducing the risk of damage and discomfort, and providing a viable alternative to existing methods.
Implementation Method 1
a water soluble cross-linker dissolved in the aqueous vehicle, wherein the water soluble cross-linker is a compound of Formula (I)... cross-links collagen
Implementation Method 2
the composition further comprises a buffer to maintain the pH within a range of 6.0 to 8.5 for at least 15 minutes
Data Source
AI summary
The present invention relates to novel pharmaceutical formulations. More specifically, the present invention relates to novel pharmaceutical formulations that are suitable for administration to the eye. The present invention also relates to the use of these formulations for the treatment of collagenic eye disorder such as, for example, the treatment of keratoconus.