Poly-gamma-glutamic acid and ICG complex for sentinel lymph node detection

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Solution Overview

Problem

Conventional methods for detecting sentinel lymph nodes using radiopharmaceuticals face challenges such as radiation exposure and contamination, and existing optical imaging probes like Indocyanine Green (ICG) have issues with short retention time in sentinel lymph nodes and high migration to other lymph nodes, making it difficult to accurately distinguish during surgical operations.

Innovation Solution

A complex of poly-gamma-glutamic acid (γ-PGA) and Indocyanine Green (ICG) is developed, which forms a stable near-infrared fluorescent probe that remains in sentinel lymph nodes for an extended period with reduced migration to other lymph nodes, enhancing detection accuracy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If Indocyanine Green (ICG) is used as an optical imaging probe, then the detection can be performed without radiation exposure, but the retention time in sentinel lymph nodes is short and migration to other lymph nodes is high

Engineering Contradiction:

Improveradiation exposureVSAvoidretention time in sentinel lymph node

Core Design Contradiction:

Object-affected harmful factorsVSDuration of action of moving object

Solution Approach 1:

The patent combines ICG with poly-gamma-glutamic acid to form a composite probe. The polymer conjugate increases the molecular size and decreases renal clearance, thereby extending retention time in lymph nodes while maintaining the fluorescent properties of ICG for radiation-free detection.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent modifies the molecular weight and clearance characteristics of ICG by conjugating it with poly-gamma-glutamic acid. This parameter change (increased molecular size) alters the pharmacokinetics to reduce renal excretion and extend retention time in the sentinel lymph node.

Inventive Principle:

Principle #35Parameter changes

2Object-affected harmful factors

If Indocyanine Green (ICG) is used for sentinel lymph node detection, then the procedure is radiation-free, but the signal intensity decreases over time due to rapid clearance

Engineering Contradiction:

Improveradiation exposureVSAvoidsignal intensity duration

Core Design Contradiction:

Object-affected harmful factorsVSDuration of action of stationary object

Solution Approach 1:

The poly-gamma-glutamic acid/ICG composite probe maintains signal intensity over time by reducing the rate of clearance. The polymer conjugate slows down renal excretion, allowing the fluorescent signal to persist longer in the sentinel lymph node for extended observation periods.

Inventive Principle:

Principle #40Composite materials

3Measurement precision

If conventional radiopharmaceutical methods are used, then detection accuracy is high, but contamination of analyzer and analysis room occurs

Engineering Contradiction:

Improvedetection accuracyVSAvoidcontamination

Core Design Contradiction:

Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent replaces radiopharmaceutical methods with optical imaging using fluorescent probes. This substitution eliminates radioactive contamination of analyzers and analysis rooms while maintaining detection accuracy through fluorescent signal visualization of the sentinel lymph node.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

4Measurement precision

If radiopharmaceuticals are used for sentinel lymph node detection, then the method is established and accurate, but disposal of radioactive samples becomes problematic

Engineering Contradiction:

Improvedetection accuracyVSAvoidradioactive waste disposal

Core Design Contradiction:

Measurement precisionVSLoss of substance

Solution Approach 1:

The patent replaces radioactive tracers with non-radioactive fluorescent probes. This eliminates the entire waste disposal problem associated with radioactive materials, as the fluorescent probe can be disposed of as常规 chemical waste after the surgical procedure.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 γ-PGA/ICG complex maintains fluorescence intensity over time and provides strong, sustained signals in sentinel lymph nodes, allowing for effective and accurate detection without radiation exposure, improving surgical precision.

Implementation Method 1

Indocyanine Green (ICG) is a typical biocompatible optical imaging probe showing fluorescent characteristics in a near-infrared region (700-1300 nm)

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS9623121B2Optical-imaging probe for detecting sentinel lymph nodes which contains a composite of poly-gamma-glutamic acid and an optical-imaging dye

Publication Date: 2017.04.18 BIOLEADERS CORP

AI summary

The present invention relates to an optical imaging probe for detecting a sentinel lymph node, which contains a complex of poly-gamma-glutamic acid and an optical imaging dye, and more particularly to an optical imaging probe for detecting a sentinel lymph node, which contains a poly-gamma-glutamic acid/optical imaging dye complex that, when injected subcutaneously in vivo, remains in the sentinel lymph node for a relatively long period of time and has a low tendency to migrate to other lymph nodes. The present invention provides a poly-gamma-glutamic acid/fluorescent dye complex, which contains no radiopharmaceutical and is harmless to the human body. The use of the poly-gamma-glutamic acid/fluorescent dye complex makes it possible to accurately detect the position of a sentinel lymph node in real time without concerns about radioactive contamination.