PPAR and FXR Agonist Combination for NAFLD Treatment
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Solution Overview
Problem
Current treatments for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are inadequate, with no approved therapies and existing treatments posing risks such as cardiac failure, osteoporosis, and neuropsychiatric disruptions, highlighting the need for effective and safe therapeutic options.
Innovation Solution
A combination product comprising a PPAR agonist, specifically Elafibranor, and a FXR agonist, such as Obeticholic acid or INT-767, is administered to patients, allowing for synergistic effects that reduce the required dosage of each component by up to a factor of 10, thereby enhancing therapeutic benefits while minimizing adverse effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If thiazolidinediones (Rosiglitazone and Pioglitazone) are used to treat NASH, then liver condition improves, but risks of congestive cardiac failure, osteoporosis, and weight gain increase
Solution Approach 1:
The patent combines a PPARα agonist and a PPARγ agonist into a single pharmaceutical composition. This merging of two different PPAR agonists with complementary mechanisms of action allows for synergistic therapeutic effects on NASH while potentially reducing the dosage and adverse effects associated with using either agent alone, particularly the cardiac and osteoporosis risks of PPARγ agonists.
Solution Approach 2:
The invention creates a composite therapeutic agent by formulating a combination of two distinct PPAR agonists (PPARα and PPARγ) into a single pharmaceutical composition. This composite approach leverages the metabolic benefits of PPARα activation (lipid metabolism) alongside the insulin-sensitizing effects of PPARγ activation, achieving broader therapeutic coverage with potentially reduced side effects.
2Reliability
If PPARα agonists and PPARγ agonists are administered separately, then therapeutic effects are achieved, but adverse effects occur
Solution Approach 1:
The patent merges two separate PPAR agonist therapies into a single combined pharmaceutical composition. This allows for synergistic therapeutic effects while enabling dose reduction of individual components, thereby minimizing the adverse effects that occur when each agent is administered at full therapeutic dosage separately.
3Reliability
If higher doses of single agents are used to achieve therapeutic effect, then liver condition improves, but adverse drug effects increase
Solution Approach 1:
By combining two PPAR agonists with different mechanisms of action into a single composition, the patent enables achievement of therapeutic effects at lower doses of each individual agent. The synergistic interaction between PPARα and PPARγ agonists allows for reduced dosing while maintaining or improving therapeutic efficacy, thereby reducing dose-dependent adverse effects.
Solution Approach 2:
The invention changes the dosing parameters by using a combination approach rather than high-dose monotherapy. The synergistic effect of combining PPARα and PPARγ agonists allows for optimization of dosage parameters, achieving therapeutic thresholds with lower individual drug doses and thus reducing adverse effects.
Data Source
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AI summary
The present invention relates to a combination of active ingredients for use in the treatment of diseases.