Multi-Phase Liquid Composition for Drug Permeability Measurement

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Solution Overview

Problem

Current methods for measuring drug permeability through cell membranes, such as Caco-2 Assay and PAMPA, are either costly and time-consuming or lack accuracy, particularly in the early stages of drug development, and do not effectively replicate the characteristics of actual cell membranes.

Innovation Solution

A multi-phase liquid composition with a lipid bilayer similar to actual cell membranes, comprising a first aqueous phase, a second aqueous phase, and an organic phase, where the lipid bilayer is formed between the two aqueous phases, allowing for the measurement of drug transport using UV spectroscopy or concentration confirmation, and a device and method for measuring drug permeability using this composition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If Caco-2 Assay using actual cells is employed to measure drug permeability, then measurement accuracy and reliability are improved, but time consumption and cost increase significantly

Engineering Contradiction:
Improvedrug permeability measurement accuracyVSAvoidtime required for cell culture
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent creates artificial lipid bilayer membranes that copy the essential structure and function of actual cell membranes. By using simplified lipid bilayer models instead of complex living cells, the system reproduces the key permeability characteristics needed for drug assessment while eliminating the time-consuming cell culture process. The lipid bilayer is formed by dissolving lipids in an organic solvent and allowing them to self-assemble at the interface between aqueous phases, creating a functional analog of cell membranes.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent employs disposable artificial lipid bilayer membranes that can be quickly prepared and discarded after use. These short-lived but functional membrane models replace expensive, long-term cell cultures. The lipid bilayer system requires minimal preparation time and can be rapidly deployed for permeability measurements, making it economically advantageous for early-stage drug screening where numerous candidates need rapid evaluation.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Productivity

If PAMPA using artificial cell membranes is used for rapid drug candidate selection, then time and cost are reduced, but measurement accuracy and cell membrane characteristic replication are compromised

Engineering Contradiction:
Improvespeed of drug candidate screeningVSAvoidcell membrane permeability measurement accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent optimizes the lipid composition and physical parameters of the artificial membrane to better match actual cell membrane properties. By carefully selecting lipid types, concentrations, and organic solvents, the system adjusts membrane thickness, fluidity, and permeability characteristics to more closely resemble biological membranes. This parameter optimization enables PAMPA to maintain high screening speed while significantly improving measurement accuracy and biological relevance.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite lipid formulations combining multiple lipid types to create artificial membranes with enhanced biological fidelity. The composite material approach allows incorporation of different phospholipids, cholesterol, and other membrane components that work together to replicate the complex structure and function of cell membranes. This composite strategy improves permeability measurement accuracy while maintaining the rapid screening capabilities of artificial membrane systems.

Inventive Principle:
Principle #40Composite materials

3Ease of manufacture

If artificial cell membranes are used instead of actual cells, then cost and time requirements are reduced, but the ability to reflect passive and active transport effects is diminished

Engineering Contradiction:
Improvecost and time efficiencyVSAvoidreflection of transport effects
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent extracts and isolates the essential passive transport function from complex cell systems. By removing the biological complexity of living cells and retaining only the lipid bilayer structure responsible for passive diffusion, the system achieves cost and time efficiency while maintaining reliable measurement of passive transport effects. The artificial membrane selectively captures the permeability function needed for early-stage drug screening without the confounding variables of active transport mechanisms.

Inventive Principle:
Principle #2Taking out (Extraction)

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 multi-phase liquid composition enables more accurate and efficient measurement of drug transport and permeability, mimicking actual cell membranes, thereby facilitating earlier and more precise drug development by reducing time and costs.

Implementation Method 1

a lipid bilayer existing between the first aqueous phase and the second aqueous phase

Methodology Applied
Scientific EffectLipid bilayer formation: Self-Assembly

Implementation Method 2

an organic phase making contact with a part or all of at least one of the first aqueous phase and the second aqueous phase

Methodology Applied
Scientific EffectDissolution: Solvation

Implementation Method 3

can more easily and accurately measure the transport of drugs and the transport speed thereof through various methods such as UV spectroscopy or concentration confirmation

Methodology Applied
Scientific EffectUV spectroscopy: Absorption Spectroscopy

Data Source

PatentUS11293911B2Multi-phase liquid composition, device for measuring permeability of drugs, and method for measuring permeability of drugs
Publication Date: 2022.04.05 KOREA ADVANCED INST OF SCI & TECH
  • US11293911B2 patent drawing
  • US11293911B2 patent drawing
  • US11293911B2 patent drawing

AI summary

The present invention relates to a multi-phase liquid composition including: a first aqueous phase; a second aqueous phase; a lipid bilayer; and an organic phase, a device for measuring the permeability of drugs including the multi-phase liquid composition, and a method for measuring the permeability of drugs.