Pigment-Coupled Mannosyl Serum Albumin Complex for Lymph Node Probing

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Solution Overview

Problem

Current methods for detecting lymph nodes during cancer surgery, such as using staining reagents or radioactive colloids, face challenges with visibility and accuracy due to short retention times and large particle sizes, which hinder direct visual detection and require additional imaging devices.

Innovation Solution

A pigment-coupled mannosyl serum albumin complex, where mannosyl groups bind to lymph node macrophages, combined with pigments like brilliant blue R, naphthol blue black, or Evans blue, and optionally a radioisotope, allowing for prolonged visibility and accurate detection of lymph nodes both visually and via gamma ray imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Illumination intensity

If staining reagents (albumin-conjugated pigment) are used to detect lymph nodes, then the lymph node can be dyed and detected, but the pigment does not stay in the lymph node for a long time and is not visible deep inside the tissue

Engineering Contradiction:
Improvevisibility of lymph nodeVSAvoidretention time of pigment in lymph node
Core Design Contradiction:
Illumination intensityVSDuration of action of moving object

Solution Approach 1:

The patent combines multiple detection modalities into a single composite agent: a radiopharmaceutical core (Tc-99m-labeled) provides gamma ray detectability, while coupled pigments (Evans blue, patent blue, or brilliant blue) provide visual coloration. This composite structure allows simultaneous gamma imaging and direct visual observation, resolving the contradiction between visibility and retention time by adding complementary detection mechanisms rather than relying on pigment retention alone

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If radioactive colloids are used to accumulate in the outpost lymph node, then high detection efficiency is achieved, but the colloid particles are too big in size and cannot move to the lymph node after injection

Engineering Contradiction:
Improvedetection accuracy of lymph node locationVSAvoidparticle size
Core Design Contradiction:
Measurement precisionVSLength of moving object

Solution Approach 1:

The patent segments the detection function into two independent components: a small radiopharmaceutical core (Tc-99m-labeled compound) that can easily migrate to the lymph node due to its small size, and a separate pigment component that provides visual detection. This segmentation allows the active core to reach the target efficiently while the pigment provides the necessary visual signal, resolving the contradiction between particle size and detection accuracy

Inventive Principle:
Principle #1Segmentation

3Adaptability or versatility

If Tc-99m-MSA labeled with indocyanine green is used for lymph node detection, then both gamma ray detection and near-infrared fluorescence imaging are achieved, but a special device is required and direct visual observation is not possible

Engineering Contradiction:
Improvedetection methods availableVSAvoidimaging equipment required
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies local quality by selecting pigments with specific spectral properties - visible light-absorbing pigments (Evans blue, patent blue, brilliant blue) that can be directly observed by the human eye in the visible spectrum. This localized optimization for visible light detection eliminates the need for complex near-infrared imaging devices while maintaining gamma ray detection capabilities through the Tc-99m label, resolving the contradiction between detection versatility and device complexity

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 complex enables prolonged retention and visualization of lymph nodes with the naked eye, enhancing surgical precision and detection rates while allowing for concurrent gamma ray imaging, facilitating direct surgical observation without the need for additional imaging devices.

Implementation Method 1

mannosyl groups bind to lymph node macrophages

Methodology Applied
Scientific EffectMannose receptor binding: Adsorption

Implementation Method 2

pigment-coupled mannosyl serum albumin complex... allows for prolonged visibility and accurate detection of lymph nodes both visually

Methodology Applied
Scientific EffectPigment absorption and reflection: Absorption (EM radiation)

Implementation Method 3

optionally a radioisotope, allowing for prolonged visibility and accurate detection of lymph nodes both visually and via gamma ray imaging

Methodology Applied
Scientific EffectGamma ray emission: Radioactive Decay

Data Source

PatentEP3597224B1Pigment-coupled mannosyl serum albumin complex and lymph node-probing composition comprising same
Publication Date: 2022.01.12 SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION
  • EP3597224B1 patent drawingFigure 1
  • EP3597224B1 patent drawingFigure 2
  • EP3597224B1 patent drawingFigure 3

AI summary

The present invention relates to a pigment-coupled mannosyl serum albumin complex and a lymph node-probing composition comprising the same. More particularly, when administered to mice, a pigment-coupled mannosyl serum albumin complex can be observed with the naked eye to exist in a condense state for a long period of time in the inguinal lymph node. Thus, the complex and a composition comprising the same can be useful for probing lymph nodes.