Polyanionic Cyclodextrin Complexes for Renal Protection

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Solution Overview

Problem

Nephrotoxic drugs cause renal damage through various mechanisms, leading to acute oliguric renal failure, and existing solutions do not adequately address the extent of renal toxicity associated with these drugs.

Innovation Solution

Compositions comprising an anionically substituted oligosaccharide, such as a polyanionic cyclodextrin derivative, are used in conjunction with nephrotoxic drugs to inhibit their nephrotoxic effects, reducing renal damage by forming complexes that minimize toxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If nephrotoxic drugs are administered at high doses to achieve maximum therapeutic efficiency, then the therapeutic effect is improved, but renal toxicity is significantly worsened

Engineering Contradiction:
Improvetherapeutic efficiencyVSAvoidrenal toxicity
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent uses cyclodextrin derivatives as intermediary substances that form inclusion complexes with nephrotoxic drugs. The cyclodextrin molecule acts as a mediator, with its hydrophobic cavity encapsulating the drug molecule, thereby modifying the drug's interaction with renal tissues and reducing nephrotoxicity while preserving therapeutic efficacy.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the chemical parameters of the drug delivery system by using cyclodextrin derivatives with different substitution patterns (e.g., sulfobutyl ether, carboxymethyl groups). These parameter changes in the cyclodextrin structure affect the complexation efficiency and nephroprotective properties, allowing optimization of the therapeutic window.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If conventional nephroprotection methods are used, then some renal protection is achieved, but the extent of nephrotoxicity reduction is insufficient

Engineering Contradiction:
Improvenephrotoxicity reductionVSAvoidadequacy of protection
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent employs composite material systems consisting of cyclodextrin derivatives combined with specific counterions (e.g., sodium, potassium) and co-solvents. This composite approach creates a synergistic effect that enhances nephroprotection beyond what single substances can achieve, providing more reliable renal protection.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The cyclodextrin derivative molecules exhibit local quality differentiation with hydrophilic outer surfaces and hydrophobic inner cavities. This local quality allows selective interaction: the hydrophobic cavity binds the drug while the hydrophilic exterior maintains solubility and reduces renal tubular accumulation, achieving superior nephroprotection.

Inventive Principle:
Principle #3Local quality

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 polyanionic oligosaccharides significantly reduces renal pathology scores and nephrotoxicity in animal models, demonstrating a protective effect against drugs like methotrexate, doxorubicin, and cisplatin, indicating a substantial inhibition of renal damage.

Implementation Method 1

Compositions comprising an anionically substituted oligosaccharide, such as a polyanionic cyclodextrin derivative, are used in conjunction with nephrotoxic drugs to inhibit their nephrotoxic effects, reducing renal damage by forming complexes that minimize toxicity.

Methodology Applied
Scientific EffectComplex formation:

Data Source

PatentEP1954292B1Compositions useful for reducing nephrotoxicity and methods of use thereof
Publication Date: 2014.05.07 VERROW PHARMA
  • EP1954292B1 patent drawingFigure 1
  • EP1954292B1 patent drawingFigure 2
  • EP1954292B1 patent drawingFigure 3

AI summary

The present invention provides compositions and methods to reduce renal damage caused by nephrotoxic drugs. The invention provides compositions comprising an anionically substituted oligosaccharide, a nephrotoxic drug and a pharmaceutically acceptable carrier, where the oligosaccharide is present in an amount effective for substantially inhibiting the nephrotoxic effect of the drug.