Micronized 2,4,6-triiodophenol for Stable Plasma Concentration

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Solution Overview

Problem

2,4-disubstituted phenol derivatives used for treating leukotriene-mediated diseases face pharmacokinetic and therapeutic challenges due to difficulty in maintaining a stable concentration range during multiple administration regimes, leading to inadequate therapeutic index and tolerability issues.

Innovation Solution

A micronized composition of 2,4,6-triiodophenol with particle sizes below 20 microns and low water content, optimized for improved pharmacokinetic properties and efficacy, is developed for treating leukotriene-mediated diseases such as pulmonary fibrosis and arthritis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If non-micronized 2,4,6-triiodophenol is administered in multiple doses, then the compound accumulates in the body, but the plasma concentration cannot be maintained within a desired therapeutic range

Engineering Contradiction:
Improvecompound accumulationVSAvoidplasma concentration stability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent applies micronization to change the physical parameter of particle size of 2,4,6-triiodophenol from non-micronized form to micronized form with particle size below 20 microns. This parameter change improves dissolution rate and bioavailability, enabling better control of plasma concentration within the therapeutic range while maintaining appropriate accumulation levels during multiple dose administration

Inventive Principle:
Principle #35Parameter changes

2Reliability

If derivatives of 2,4-disubstituted phenols are used as inhibitors, then therapeutic activity against leukotriene-mediated diseases is achieved, but pharmacokinetic and tolerability drawbacks occur

Engineering Contradiction:
Improvetherapeutic activityVSAvoidpharmacokinetic and tolerability drawbacks
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the physical parameter of the compound from non-micronized to micronized form with particle size below 20 microns. This parameter change improves dissolution rate and bioavailability, leading to more predictable pharmacokinetics and reduced tolerability issues while preserving the therapeutic activity as iNOS inhibitor and L-selectin adhesion molecule inhibitor

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP2174654B1Micronized composition of 2,4,6-triiodophenol
Publication Date: 2012.08.22 IND FARM CANTABRIA
  • EP2174654B1 patent drawingFigure 1~2
  • EP2174654B1 patent drawingFigure 3~4
  • EP2174654B1 patent drawingFigure 5~6

AI summary

A composition comprising a 2,4-disubstituted phenol derivative in its micronized form and its use in the treatment of leukotriene-mediated diseases, gastrointestinal-inflammatory diseases or pulmonar fibrosis. More particularly, the present invention refers to use of 2,4,6-triiodophenol for the treatment of pulmonary fibrosis and arthritis.