Fumaric Acid Ester Combination to Reduce MS Treatment Side Effects
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Solution Overview
Problem
Fumaric acid esters, used in treating multiple sclerosis and psoriasis, have significant adverse side effects and limited efficacy, necessitating a formulation that enhances therapeutic efficacy while reducing dosage and side effects.
Innovation Solution
A pharmaceutical combination of 5-amino-2,3-dihydro-1,4-phthalazinedione or its pharmaceutically acceptable salts with fumaric acid esters, demonstrating a supraadditive effect in reducing pro-inflammatory cytokine release and immunobiomarkers, thereby potentially lowering the required dosage and mitigating side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If fumaric acid esters are used to treat multiple sclerosis and psoriasis, then therapeutic efficacy is achieved, but adverse side effects increase and efficacy is limited
Solution Approach 1:
The patent combines 5-amino-2,3-dihydro-1,4-phthalazinedione with fumaric acid esters in a fixed-ratio pharmaceutical composition. This merging of two active substances with different mechanisms of action (5-amino-2,3-dihydro-1,4-phthalazinedione as an immunomodulator and fumaric acid ester as an anti-inflammatory agent) creates a synergistic effect that enhances therapeutic efficacy while allowing for reduced dosages of each component, thereby reducing adverse side effects.
2Reliability
If fumaric acid esters are used at higher dosages to improve efficacy, then therapeutic effect increases, but adverse side effects worsen
Solution Approach 1:
The patent changes the dosage parameters by establishing a fixed ratio between 5-amino-2,3-dihydro-1,4-phthalazinedione and fumaric acid ester (specifically dimethyl fumarate). This parameter change allows for optimized dosing where the combined effect achieves superior therapeutic results at lower individual dosages compared to monotherapy, thereby reducing the dosage-related adverse side effects while maintaining or enhancing efficacy.
3Ease of operation
If monotherapy with fumaric acid esters is used, then treatment simplicity is maintained, but efficacy is limited and side effects are significant
Solution Approach 1:
The patent merges two active substances into a single fixed-ratio pharmaceutical composition, maintaining ease of administration (once-daily dosing) while significantly enhancing efficacy through synergistic action. The combination allows for reduced dosages of each component, thereby reducing side effects, while the unified formulation preserves treatment simplicity.
4Reliability
If fumaric acid esters are used, then immunomodulating and neuroprotective effects are achieved, but gastrointestinal problems and other adverse reactions occur
Solution Approach 1:
The patent changes the dosage parameters by establishing a fixed ratio between the two active substances. This optimization allows for reduced dosages of fumaric acid ester, thereby reducing gastrointestinal side effects, while the synergistic combination maintains or enhances the immunomodulating and neuroprotective effects.
Solution Approach 2:
The 5-amino-2,3-dihydro-1,4-phthalazinedione acts as an intermediary substance that enhances the therapeutic effect of fumaric acid ester, allowing for lower dosages of the latter. This intermediary substance contributes to the overall immunomodulating and neuroprotective effects while reducing the dosage-related gastrointestinal side effects of fumaric acid ester.
Data Source
AI summary
The present application relates to a combination of 5-amino-2,3-dihydro-1,4-phthalazinedione or one of its pharmaceutically acceptable salts and at least one fumaric acid ester or a pharmaceutically acceptable salt thereof. In particular, the invention relates to the use of 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt in said pharmaceutical combination. Pharmaceutical compositions and advantageous formulation techniques are disclosed.