Fe-tCDTA Contrast Agent Osmolality Reduction

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Solution Overview

Problem

Low-molecular gadolinium-based contrast agents used in MRI examinations are toxic due to incomplete excretion, leading to long-term accumulation in tissues, while existing iron-based contrast agents produce high-salt, high-osmolality products that are unfavorable for intravenous use.

Innovation Solution

A process to produce an Fe-tCDTA contrast agent with reduced osmolality by controlling the pH and using a specific sequence of steps involving the preparation of an aqueous solution of tCDTA and FeO(OH), followed by precipitation and adjustment of pH to minimize salt content and maximize purity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If low-molecular gadolinium-based contrast agents are used for MRI examinations, then imaging quality is improved, but long-term toxicity increases due to incomplete excretion and tissue accumulation

Engineering Contradiction:
Improveimaging qualityVSAvoidlong-term toxicity
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent changes the metal ion parameter from gadolinium to iron in the contrast agent complex, transforming it from a toxic substance with incomplete excretion to a biocompatible substance with complete metabolic pathways. This parameter change resolves the toxicity issue while maintaining the contrast enhancement function for MRI imaging.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If iron-based contrast agents are used to reduce toxicity, then safety is improved, but osmolality increases making them unfavorable for intravenous use

Engineering Contradiction:
ImprovetoxicityVSAvoidsuitability for intravenous injection
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent optimizes the ligand structure (using tcdpa) and complex composition to reduce the osmolality of the iron-based contrast agent. By adjusting these chemical parameters, the agent achieves low osmolality suitable for intravenous injection while maintaining the safety benefits of iron-based compounds.

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If conventional synthesis methods are used for iron-based contrast agents, then production is simplified, but salt content and osmolality increase

Engineering Contradiction:
Improveproduction simplicityVSAvoidsalt content
Core Design Contradiction:
Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent extracts and removes excess salt byproducts from the synthesis reaction through purification steps. By separating the desired contrast agent complex from the salt-containing mother liquor, the method reduces salt content in the final product while maintaining production feasibility.

Inventive Principle:
Principle #2Taking out (Extraction)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The resulting Fe-tCDTA contrast agent has a high degree of purity and low salt content, achieving an osmolality of less than 700 mOsm/kg, making it suitable for intravenous injection in higher dosages and potentially reducing toxicity.

Implementation Method 1

preparing an aqueous solution of tCDTA and FeO(OH)... to produce an Fe-tCDTA contrast agent

Methodology Applied
Scientific EffectComplexation: Chemical Bonding

Implementation Method 2

precipitating the Fe-tCDTA contrast agent from the aqueous solution by adding a water-miscible organic solvent, separating the precipitate

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Data Source

PatentUS11771780B2Method for preparing an Fe-tCDTA contrast agent and product obtainable by the method
Publication Date: 2023.10.03 CHARITE UNIVS MEDIZIN BERLIN

AI summary

A process is provided in which the resulting Fe-tCDTA contrast agent has a reduced osmolality. The process according to the invention comprises the following steps:a) preparing an aqueous solution of tCDTA and FeO(OH), tCDTA and FeO(OH) being present in a molar ratio of from 1:1 to 1:1.4;b) b.1) adjusting a pH of the aqueous solution to between pH 2.5 and pH 4.5 by adding a base, preferably meglumine, and separating the precipitate; orb.2) precipitating the Fe-tCDTA contrast agent from the aqueous solution by adding acetone, separating the precipitate, and preparing an aqueous solution from the precipitate; andc) adjusting a pH of the aqueous solution to between pH 6.5 and pH 8.0 by adding a base, preferably meglumine, and separating the precipitated FeO(OH).