FXR Agonist Combination Therapy for Severe Hyperlipidemia
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Solution Overview
Problem
Existing treatments for elevated lipid levels in the blood, such as cholesterol and triglycerides, are often inadequate, particularly in severe cases, and can have adverse side effects, necessitating a more effective and safer combination therapy.
Innovation Solution
A pharmaceutical composition comprising an FXR agonist in combination with PPAR-alpha, PPAR-delta, or PPAR-alpha and delta dual agonists, or fibrates, or statins, optionally with pharmaceutically acceptable carriers, to synergistically lower lipid levels and reduce liver enzyme activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a fibric acid derivative is used alone to treat hyperlipidemia, then the treatment is simple, but the effectiveness is inadequate in severe cases
Solution Approach 1:
The patent combines a fibric acid derivative with another lipid-lowering agent (statin, ezetimibe, or bile acid sequestrant) into a single pharmaceutical composition. This merging of multiple therapeutic agents addresses the inadequacy of monotherapy in severe hyperlipidemia cases while maintaining treatment simplicity through combined formulation.
2Object-affected harmful factors
If the dose of fibric acid derivative is reduced to improve side effect profile, then the side effects are reduced, but the effectiveness in controlling severe hyperlipidemia is insufficient
Solution Approach 1:
The patent combines a lower dose of fibric acid derivative with another lipid-lowering agent to achieve the therapeutic effect of a higher fibric acid derivative dose while reducing its side effects. The synergistic combination allows each agent to work at optimal doses, addressing both effectiveness and side effect concerns.
Solution Approach 2:
The second lipid-lowering agent acts as an intermediary that compensates for the reduced efficacy of the lower-dose fibric acid derivative. This mediator enables the system to achieve the desired therapeutic outcome without relying on high doses of the fibric acid derivative, thereby reducing its harmful side effects.
3Reliability
If multiple lipid-lowering agents are combined to improve effectiveness, then the potency is enhanced, but the side effect profile may worsen
Solution Approach 1:
The patent carefully controls the dosages of each lipid-lowering agent in the combination, using specific dose ranges that have been optimized to maximize efficacy while minimizing side effects. This parameter optimization ensures that the combined potency is enhanced without proportionally increasing the side effect profile.
Data Source
AI summary
The present invention relates to a pharmaceutical composition comprising a combination of an FXR agonist and at least one lipid lowering agent (e.g., PPAR-alpha agonist, PPAR-delta agonist, PPAR-alpha and delta dual agonist, and/or statin). Also disclosed is use of the combination for the treatment or prevention of a FXR mediated disease or condition, such as primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), portal hypertension, bile acid diarrhea, NAFLD (nonalcoholic fatty liver disease), NASH (non-alcohol-induced steatohepatitis), and other chronic liver diseases. The combination of the present invention is useful for the treatment or prevention of conditions related to elevated lipid and liver enzyme levels. The present invention also relates to packs or kits including the pharmaceutical combination.