Sustained-Release CCR2 Antagonist Formulations for Inflammation

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Solution Overview

Problem

Current treatments for inflammatory and immunoregulatory disorders related to chemokine activity, such as rheumatoid arthritis and obesity, face challenges due to the rapid elimination of chemokine receptor antagonists, requiring frequent administration and limited sustained release options.

Innovation Solution

Development of compounds and pharmaceutical compositions that modulate chemokine receptor activity, particularly CCR2, using specific chemical structures to inhibit chemokine binding and function, thereby treating conditions like rheumatoid arthritis, obesity, and other inflammatory diseases with improved pharmacokinetic properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If chemokine receptor antagonists are used to treat inflammatory disorders, then therapeutic efficacy is improved, but rapid elimination requires frequent administration

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidduration of action

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent applies preliminary action by developing sustained-release formulations and prodrugs that pre-load the drug delivery system with active compounds. These formulations are designed to release the chemokine receptor antagonists gradually over extended periods, eliminating the need for frequent administration while maintaining therapeutic efficacy throughout the duration.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent employs parameter changes by modifying the pharmacokinetic properties of the antagonists through formulation science. By changing the release rate parameter from immediate to sustained release, and by modifying molecular structure parameters in prodrug designs, the duration of action is extended while preserving the therapeutic efficacy of the original compounds.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If chemokine receptor antagonists are administered frequently to maintain therapeutic levels, then therapeutic efficacy is maintained, but patient compliance and treatment convenience deteriorate

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidadministration frequency

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent implements continuity of useful action through sustained-release formulations that provide continuous drug delivery over extended periods. This eliminates the interruptions and repeated administrations required by conventional formulations, thereby maintaining constant therapeutic levels while significantly improving patient convenience and compliance.

Inventive Principle:

Principle #20Continuity of useful action

3Device complexity

If limited sustained release options are used, then formulation complexity is reduced, but therapeutic duration and sustained efficacy are limited

Engineering Contradiction:

Improveformulation complexityVSAvoidsustained release duration

Core Design Contradiction:

Device complexityVSDuration of action of moving object

Solution Approach 1:

The patent uses intermediary approaches by employing prodrugs as intermediate forms that are converted to active antagonists in vivo. These prodrug intermediaries provide sustained release capabilities without requiring complex delivery devices or formulation systems, thereby extending therapeutic duration while keeping the overall system relatively simple.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS10899765B2Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation

Publication Date: 2021.01.26 CHEMOCENTRYX INC

AI summary

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists.