AT1 Blocker and CCR2 Inhibitor Combination for Chronic Kidney Disease
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments targeting the CCR2 pathway and renin-angiotensin system for kidney diseases are not effective in halting the progression of chronic renal failure, and there is a need for a more comprehensive therapeutic approach that addresses the interaction between these pathways.
Innovation Solution
A combination therapy comprising an angiotensin receptor blocker and a chemokine receptor pathway inhibitor, such as irbesartan and propagermanium, to inhibit arrestin recruitment and inositol phosphate production, targeting the chemokine receptor pathway and angiotensin receptor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monotherapy with CCR2 pathway inhibitor or angiotensin receptor blocker is used, then treatment simplicity is maintained, but therapeutic efficacy is insufficient to halt chronic renal failure progression
Solution Approach 1:
The patent combines two different therapeutic agents: a CCR2 pathway inhibitor (such as RS 504393) and an angiotensin receptor blocker (such as irbesartan or losartan) into a single combination therapy formulation. This merging of two mechanisms of action addresses the limitation of monotherapy by simultaneously blocking chemokine-mediated inflammation and renin-angiotensin system activity, thereby achieving superior therapeutic efficacy in halting chronic renal failure progression while maintaining manageable treatment complexity through unified administration.
2Reliability
If combination therapy with multiple mechanisms is used, then therapeutic efficacy is improved, but treatment complexity increases
Solution Approach 1:
The patent merges a CCR2 pathway inhibitor and an angiotensin receptor blocker into a single combination therapy that can be administered together, simplifying the treatment regimen compared to sequential or separate administrations. This unified approach maintains ease of operation by allowing concurrent dosing while achieving improved therapeutic efficacy through synergistic blockade of multiple pathogenic pathways involved in chronic renal failure.
Solution Approach 2:
The combination therapy formulation serves multiple therapeutic functions simultaneously: it blocks chemokine receptor signaling to reduce inflammation and fibrosis while also inhibiting angiotensin II receptor activity to control blood pressure and proteinuria. This multi-functionality in a single treatment regimen improves ease of operation by consolidating multiple therapeutic actions into one administered unit, enhancing patient compliance while achieving comprehensive disease management.
Data Source
Figure 1
Figure 2
Figure 3A~3E
AI summary
The invention relates to pharmaceutical compositions comprising: (a) at least one angiotensin receptor blocker or a pharmaceutically acceptable salt thereof, and (b) at least one chemokine receptor pathway inhibitor or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising: (a) at least one angiotensin receptor blocker or a pharmaceutically acceptable salt thereof; and (b) at least one chemokine receptor pathway inhibitor or a pharmaceutically acceptable salt thereof which inhibits a component of the chemokine receptor pathway other than the chemokine receptor. Oral sustained release pharmaceutical compositions comprising the pharmaceutical composition, as well as injectable sustained release pharmaceutical compositions comprising the pharmaceutical composition are described. The invention further relates to tablets, capsules, injectable suspensions, and compositions for pulmonary or nasal delivery comprising the pharmaceutical composition. Also described are: methods for assessing the efficacy of the pharmaceutical composition; methods for assessing the inhibition or partial inhibition activity of the pharmaceutical composition; methods for the treatment, amelioration or prevention of a condition or disease comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition; and the use of the pharmaceutical composition for the manufacture of a dosage form for the treatment of a disease.