Injectable Alginic Acid Hydrogel for Contrast and Drug Retention

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Solution Overview

Problem

Existing image contrast agents like indocyanine green suffer from concentration-dependent aggregation, chemical instability, and rapid diffusion, leading to reduced image discrimination and drug persistence issues, while hydrophobic and hydrophilic drugs face challenges in maintaining therapeutic effects at target sites due to rapid absorption and spread.

Innovation Solution

An alginic acid-based injectable hydrogel system using polyvalent ions as an ionic cross-linking agent, combined with a crosslinking rate controller, to form a gel at the target site, allowing image contrast agents and drugs to remain and release slowly without spreading.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If indocyanine green is used as a fluorescent contrast agent, then the lesion can be detected by fluorescence imaging, but the agent spreads rapidly to surrounding tissues reducing image discrimination accuracy

Engineering Contradiction:
Improveimage discrimination accuracyVSAvoiddiffusion rate of contrast agent
Core Design Contradiction:
Measurement precisionVSSpeed

Solution Approach 1:

The patent introduces alginic acid hydrogel as an intermediary carrier that binds to the fluorescent contrast agent. This mediator prevents direct diffusion of the free contrast agent into surrounding tissues while maintaining its fluorescence properties, thereby resolving the contradiction between detection capability and diffusion control.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite material system consisting of alginic acid hydrogel combined with fluorescent contrast agent (indocyanine green or ZW800-1). This composite structure allows the contrast agent to be delivered and retained at the target site without rapid diffusion, improving both image discrimination and localization precision.

Inventive Principle:
Principle #40Composite materials

2Illumination intensity

If indocyanine green is used at high concentration to enhance fluorescence signal, then detection sensitivity improves, but concentration-dependent aggregation reduces fluorescence brightness

Engineering Contradiction:
Improvefluorescence brightnessVSAvoidchemical stability of contrast agent
Core Design Contradiction:
Illumination intensityVSStability of the object's composition

Solution Approach 1:

The patent changes the physical state and local environment of the contrast agent by incorporating it into the alginic acid hydrogel matrix. This parameter change prevents the concentration-dependent aggregation that occurs in free solution, allowing high concentrations to be used without fluorescence quenching, thereby maintaining both brightness and chemical stability.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If drugs are injected locally to maximize therapeutic effect at target site, then treatment efficacy improves, but hydrophobic drugs are not easily soluble and hydrophilic drugs spread quickly reducing duration of action

Engineering Contradiction:
Improvetherapeutic effect at target siteVSAvoidduration of drug at injection site
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent applies local quality by creating a hydrogel formulation with specific physical properties (viscosity, gelation time) that are optimized for local injection. The alginic acid hydrogel provides a local environment that retains both hydrophobic and hydrophilic drugs at the injection site, preventing systemic diffusion while maintaining solubility and therapeutic efficacy.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses composite material formulation by combining alginic acid hydrogel with drugs of different solubility characteristics. This composite system provides a unified delivery platform that solves the solubility and retention problems for both hydrophobic and hydrophilic drugs simultaneously, extending duration of action while maintaining target site efficacy.

Inventive Principle:
Principle #40Composite materials

4Measurement precision

If Indian ink is injected to label lesion for surgical resection, then the region can be visually identified, but the ink spreads around the injected area widening the resection range

Engineering Contradiction:
Improvelesion location accuracyVSAvoidresection area
Core Design Contradiction:
Measurement precisionVSArea of stationary object

Solution Approach 1:

The patent uses alginic acid hydrogel as an intermediary carrier for the contrast agent, replacing direct injection of free-flowing Indian ink. This mediator prevents the ink from spreading beyond the injection site while maintaining sufficient concentration for visual identification, thereby preserving lesion location accuracy and minimizing resection area.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 system enables accurate image labeling and prolonged drug efficacy at the target site by preventing diffusion, enhancing image discrimination and reducing side effects on surrounding tissues.

Implementation Method 1

An alginic acid-based injectable hydrogel system using polyvalent ions as an ionic cross-linking agent

Methodology Applied
Scientific EffectIonic cross-linking: Chemical Bonding

Implementation Method 2

to form a gel at the target site

Methodology Applied
Scientific EffectGel formation: Gel

Implementation Method 3

releasing the drug contained in alginic acid at the target site

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP3878476B1Alginic acid-based injectable hydrogel system
Publication Date: 2025.10.01 NATIONAL CANCER CENTER(JP)
  • EP3878476B1 patent drawingFigure 1~2A
  • EP3878476B1 patent drawingFigure 2B~2C
  • EP3878476B1 patent drawingFigure 3A~3B

AI summary

The present invention provides an alginic acid-based injectable hydrogel system for labeling an accurate position of a disease lesion and effectively delivering a drug to a target region. The formulation of the present invention can make it easy to locally inject a contrast agent and a drug into a target region while controlling the release rate of the contrast agent or the drug, with the formation of the hydrogel in the injected region. Through the advantages, the labeled position can be accurately determined from images, thereby enhancing the precision of surgical operation, with a minimal incision formed therefor. In addition, when used, the alginic acid-based injectable hydrogel system allows the effective local delivery of a drug to a target region while increasing the long-acting effect of the drug.