Microneedle Coating Composition Stabilizing Vaccine Antigen

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Solution Overview

Problem

Existing microneedle coating compositions fail to stabilize physiologically active substances like proteins due to insufficient stability when certain materials are used as thickeners.

Innovation Solution

A microneedle coating composition comprising Japanese encephalitis vaccine antigen, a basic amino acid, and an acid with a specific mole ratio, where the acid is selected from phosphoric acid, lactic acid, benzoic acid, maleic acid, citric acid, tartaric acid, succinic acid, or ascorbic acid, and the basic amino acid is arginine or lysine, which improves the stability of the antigen.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If thickeners are used in microneedle coating composition, then the coating can be formed, but the stability of physiologically active substances is insufficient

Engineering Contradiction:
Improvestability of physiologically active substancesVSAvoidcoating formation reliability
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The patent changes the chemical parameters of the coating composition by using basic amino acids (arginine, lysine) instead of conventional thickeners, and controlling the mole ratio of acid to basic amino acid within 1/(N+1) to 2, where N is the valence of the acid. This parameter optimization maintains coating formability while significantly improving the stability of physiologically active substances like proteins and peptides.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite coating system combining basic amino acids with acids (organic or inorganic) in specific molar ratios. This composite approach using arginine or lysine combined with acids like citric acid, phosphoric acid, or lactic acid provides both the structural integrity needed for coating formation and the chemical environment necessary for stabilizing biologically active substances.

Inventive Principle:
Principle #40Composite materials

2Quantity of substance

If the mole number of acid for one mole of basic amino acid is 1/(N+1) or less, then the composition can dissolve the basic amino acid, but the content of acid is low and cannot dissolve the basic amino acid

Engineering Contradiction:
Improvesolubility of basic amino acidVSAvoidstability of Japanese encephalitis vaccine antigen
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent precisely controls the mole ratio parameter of acid to basic amino acid within the range of greater than 1/(N+1) and less than 2. This optimized ratio ensures sufficient acid content to dissolve and stabilize the basic amino acid while maintaining the stability of the Japanese encephalitis vaccine antigen, resolving the contradiction between solubility and stability.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If the mole number of acid for one mole of basic amino acid is 2 or more, then the basic amino acid can dissolve, but the concentration of basic amino acid is low and the stability of antigen is reduced

Engineering Contradiction:
Improveconcentration of basic amino acidVSAvoidstability of Japanese encephalitis vaccine antigen
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent optimizes the acid to basic amino acid mole ratio to be greater than 1/(N+1) and less than 2, preventing excessive acid content that would dilute the basic amino acid concentration and reduce antigen stability. This parameter control maintains high concentration of stabilizing agents while preserving antigen integrity.

Inventive Principle:
Principle #35Parameter changes

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 composition effectively stabilizes the Japanese encephalitis vaccine antigen, ensuring its stability and efficacy when administered through the microneedle device, with arginine and lysine hydrochloride enhancing the antigen's stability and concentration.

Implementation Method 1

a microneedle coating composition comprising a Japanese encephalitis vaccine antigen, a basic amino acid, and an acid, wherein the mole number of the acid for one mole of the basic amino acid is larger than 1/(N+1) and less than 2

Methodology Applied
Scientific EffectNeutralization reaction: Chemical Bonding

Data Source

PatentEP2957298B1Microneedle coating composition and microneedle device
Publication Date: 2018.11.28 HISAMITSU PHARM CO INC
  • EP2957298B1 patent drawingFigure 1
  • EP2957298B1 patent drawingFigure 2
  • EP2957298B1 patent drawingFigure 3(a)~3(c)

AI summary

Disclosed is a microneedle coating composition comprising a Japanese encephalitis vaccine antigen, a basic amino acid, and an acid, wherein the mole number of the acid for one mole of the basic amino acid is larger than 1/(N+1) and less than 2, where N represents the valence of the acid.