Derivatized Cyclodextrin Gadolinium Chelation for NSF Reduction

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Solution Overview

Problem

Gadolinium-based contrast agents used in MRI can cause toxicity due to reduced renal excretion, particularly in patients with compromised renal function, leading to conditions like nephrogenic systemic fibrosis (NSF), as they release toxic gadolinium ions if retained in the body for extended periods.

Innovation Solution

Compositions comprising a gadolinium-based contrast agent and a derivatized cyclodextrin, such as sulfobutyl ether or hydroxypropyl cyclodextrin, with a molar ratio greater than 1:1, are used to inhibit or ameliorate the toxic effects by enhancing renal excretion of gadolinium, thereby reducing the risk of NSF.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If gadolinium-based contrast agents are administered to improve MRI image visibility, then diagnostic imaging quality is improved, but toxicity and risk of nephrogenic systemic fibrosis increase in patients with compromised renal function

Engineering Contradiction:

ImproveMRI image visibilityVSAvoidgadolinium toxicity

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a mediator substance (such as a chelating agent or protective compound) that binds to gadolinium ions, preventing their toxic interaction with tissues while allowing the contrast agent to maintain its imaging function. This intermediary substance reduces gadolinium toxicity without compromising MRI image quality.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies chemical parameters of the contrast agent formulation, such as adjusting pH, adding co-administered compounds, or using alternative chelators, to reduce gadolinium ion release and toxicity while preserving the contrast enhancement properties needed for diagnostic imaging.

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If gadolinium-based contrast agents are used to enhance MRI imaging, then diagnostic capability is improved, but renal excretion burden increases leading to gadolinium retention

Engineering Contradiction:

Improveinternal structure visibilityVSAvoidrenal excretion efficiency

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent employs a mediator compound that facilitates the excretion of gadolinium by the kidneys or provides an alternative elimination pathway, reducing retention and improving reliability in patients with compromised renal function while maintaining imaging effectiveness.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent extracts or removes the toxic gadolinium ions from the body more efficiently through enhanced excretion mechanisms, possibly by introducing substances that promote renal clearance or provide alternative elimination routes, thereby reducing retention and associated risks.

Inventive Principle:

Principle #2Taking out (Extraction)

3Ease of operation

If gadolinium-based contrast agents are administered to patients with compromised renal function, then MRI imaging can be performed, but the risk of nephrogenic systemic fibrosis increases

Engineering Contradiction:

ImproveMRI imaging availabilityVSAvoidnephrogenic systemic fibrosis risk

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by administering protective substances or modifying the contrast agent formulation before gadolinium administration to prevent toxic effects, allowing MRI imaging to proceed safely in high-risk patients while preventing NSF development.

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The patent converts the potentially harmful gadolinium ions into a beneficial or neutral form through chelation or chemical modification, allowing the contrast agent to maintain its diagnostic utility while eliminating the risk of nephrogenic systemic fibrosis in patients with compromised renal function.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

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 use of derivatized cyclodextrins in conjunction with gadolinium-based contrast agents significantly enhances the excretion of gadolinium, reducing its toxic accumulation in the body and minimizing the risk of NSF, especially in patients with impaired renal function.

Implementation Method 1

compositions comprising a gadolinium-based contrast agent, a derivatized cyclodextrin, and optionally a pharmaceutically acceptable carrier or diluent

Methodology Applied

Scientific EffectInclusion complex formation: Solvation

Data Source

PatentUS8192721B2Compositions useful for reducing toxicity associated with gadolinium-based contrast agents

Publication Date: 2012.06.05 VERROW PHARMA

AI summary

The invention relates to compositions comprising a gadolinium-based contrast agent and a derivatized cyclodextrin. Further provided are methods for reducing the toxicity associated with gadolinium-based contrast agents.