Isoquercitrin Solubility via L-Arginine and Ascorbate Complexes

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Solution Overview

Problem

Isoquercitrin has low oral absorption due to its relatively low water solubility, requiring high doses for bioavailability, and existing modifications like enzymatically modified isoquercitrin are impractical for human use as they are mixtures of bioactive derivatives, violating FDA guidelines.

Innovation Solution

A water-soluble pharmaceutical composition containing isoquercitrin, L-arginine, and an alkali salt of ascorbic acid, with a specific molar ratio, enhancing bioavailability without the drawbacks of existing modifications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high doses of isoquercitrin are administered to achieve sufficient bioavailability, then absorption is improved, but the dose becomes unusually high compared to typical pharmaceuticals

Engineering Contradiction:
ImprovebioavailabilityVSAvoiddose
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent introduces L-arginine and ascorbic acid alkali salt as intermediary substances that facilitate isoquercitrin absorption. These mediators form complexes with isoquercitrin, improving its water solubility and facilitating transport across the intestinal membrane, thereby achieving better bioavailability at lower doses.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameters of isoquercitrin by combining it with L-arginine and ascorbic acid alkali salt in specific molar ratios (1:1.6-2.6:0.16-1.95). This parameter modification alters the solubility and permeation characteristics of isoquercitrin, enabling improved absorption without requiring unusually high doses.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If enzymatically modified isoquercitrin is used to improve water solubility, then bioavailability is improved, but the composition becomes a mixture of multiple bioactive derivatives that is impractical for human use

Engineering Contradiction:
ImprovebioavailabilityVSAvoidcomposition complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and isolates specific functional components (L-arginine and ascorbic acid alkali salt) that are responsible for improving isoquercitrin solubility and absorption. Instead of using a complex mixture of enzymatically modified derivatives, the patent identifies and combines these key components in a simplified formulation that maintains bioavailability improvement while reducing compositional complexity.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies local quality modification by selectively modifying isoquercitrin through combination with L-arginine and ascorbic acid alkali salt, rather than performing broad enzymatic modification that produces multiple derivatives. This localized approach modifies only the necessary properties (solubility and permeation) while maintaining the integrity of the main isoquercitrin molecule.

Inventive Principle:
Principle #3Local quality

3Ease of manufacture

If isoquercitrin is administered alone, then the formulation is simple, but water solubility is low resulting in poor oral absorption

Engineering Contradiction:
Improveformulation simplicityVSAvoidoral absorption
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent merges isoquercitrin with L-arginine and ascorbic acid alkali salt in a single pharmaceutical composition. This combination creates a synergistic effect where the merged formulation maintains relative simplicity while dramatically improving water solubility and oral absorption through the cooperative action of all three components.

Inventive Principle:
Principle #5Merging (Combining)

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 significantly improves isoquercitrin absorption, achieving higher plasma concentrations and bioavailability, as demonstrated by increased permeation rates and pharmacokinetic profiles compared to isoquercitrin alone, with improved stability and bioavailability metrics.

Implementation Method 1

Enzymatically modified isoquercitrin (EMIQ) with higher water solubility has been developed to improve the bioavailability of isoquercitrin

Methodology Applied
Scientific EffectWater solubility enhancement: Solvation

Implementation Method 2

The composition significantly improves isoquercitrin absorption, achieving higher plasma concentrations and bioavailability, as demonstrated by increased permeation rates and pharmacokinetic profiles

Methodology Applied
Scientific EffectPermeation: Permeation

Data Source

PatentEP3685825B1Isoquercitrin compositions
Publication Date: 2023.11.01 ALPS PHARMA IND CO LTD
  • EP3685825B1 patent drawingFigure 1
  • EP3685825B1 patent drawing

AI summary

A water-soluble pharmaceutical composition containing isoquercitrin, L-arginine, and ascorbic acid or an alkali salt thereof, in which the molar ratio between the isoquercitrin, L-arginine, and the ascorbic acid or alkali salt is 1: 1.6-2.6: 0.16-1.95.