Antibubble Encapsulation with Gaseous Mediator

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Solution Overview

Problem

Current encapsulation technologies, such as microbubbles and antibubbles, face challenges in achieving stable 3-phase systems with a gaseous middle phase, particularly in sizes smaller than a millimeter and with a lifetime of at least 10 minutes, due to instability and incomplete release of encapsulated compounds, especially when triggered by ultrasound.

Innovation Solution

A method for producing stable 3-phase systems involves creating a 2-phase system with a volatile organic liquid as the continuous phase, dispersing it in a third phase, and removing the volatile compound through freeze-drying to form a gaseous phase, stabilized by colloidal particles adsorbed on the interfaces, allowing for extended lifetime and controlled release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Volume of moving object

If antibubbles are produced with size smaller than 1 mm, then they are more suitable for practical applications, but their lifetime becomes too short (order of seconds) for practical use

Engineering Contradiction:
Improveantibubble sizeVSAvoidantibubble lifetime
Core Design Contradiction:
Volume of moving objectVSDuration of action of stationary object

Solution Approach 1:

The patent introduces a gaseous intermediate phase between the inner liquid phase and outer liquid phase. This gaseous phase acts as a mediator that provides mechanical support and prevents direct contact between the inner and outer liquid phases, thereby preventing coalescence and extending the lifetime of small antibubbles to at least 10 minutes while maintaining practical sizes below 1 mm

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical state parameter of the middle phase from liquid to gas. This parameter change fundamentally alters the stability characteristics of the antibubble system, allowing small antibubbles to maintain their structure for extended periods by preventing the rapid coalescence that occurs in traditional liquid-based antibubbles

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If microbubbles are used for triggered release of compounds, then release can be triggered using ultrasound, but the amount of active compound that can be loaded is generally low and release is generally incomplete

Engineering Contradiction:
Improvetriggered release capabilityVSAvoidamount of active compound loaded
Core Design Contradiction:
Ease of operationVSQuantity of substance

Solution Approach 1:

The patent employs a nested structure with three phases where the inner liquid phase containing the active compound is embedded within a gaseous phase, which is in turn embedded within an outer liquid phase. This nested configuration provides multiple interfaces and compartments for compound loading, significantly increasing the total loading capacity while maintaining ultrasound-triggered release functionality

Inventive Principle:
Principle #7Nested doll (Nesting)

Solution Approach 2:

The patent creates a composite three-phase system combining liquid, gas, and liquid phases with distinct properties. This composite structure allows optimization of each phase for specific functions: the inner liquid phase for compound containment, the gaseous phase for structural stability and compressibility, and the outer liquid phase for stability and trigger response, achieving both high loading capacity and complete release

Inventive Principle:
Principle #40Composite materials

3Productivity

If high levels of ultrasound are applied to trigger release from microbubbles, then release can be achieved, but side effects may occur in mammals

Engineering Contradiction:
Improverelease efficiencyVSAvoidside effects in mammals
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent creates local quality differences across the three phases, with the gaseous middle phase providing a localized region of high compressibility and elasticity. This allows the antibubble to respond to low levels of ultrasound by compressing and expanding the gaseous phase, which triggers complete release of the encapsulated compound without requiring high ultrasound levels that would cause harmful side effects

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

This approach results in 3-phase systems with a gaseous middle phase that are stable for several hours to days, enabling effective encapsulation and controlled release of compounds, suitable for pharmaceutical and food applications, with antibubbles having a diameter smaller than 1 mm and a lifetime of at least 3 minutes.

Implementation Method 1

stable 3-phase systems... stabilized by adsorption of colloidal particles on an interface that separates two phases of the 3-phase system

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

removing the volatile compound through freeze-drying to form a gaseous phase

Methodology Applied
Scientific EffectFreeze-drying: Freeze Drying

Data Source

PatentEP2885073B1Encapsulation system
Publication Date: 2019.07.10 BETHER ENCAPSULATES BV
  • EP2885073B1 patent drawingFigure 1(a)~1
  • EP2885073B1 patent drawingFigure 2
  • EP2885073B1 patent drawingFigure 3a~3b

AI summary

The invention pertains to an encapsulation system; in particular a 3- phase system comprising an inner, second and outer phase wherein the second phase is gaseous, and wherein the 3-phase system has a lifetime of at least 3 min and the second phase has a diameter of less than 1 mm. An example of such a system is a stable, small antibubble. Also, the invention pertains to methods of making such 3-phase systems, and to use and methods of use thereof. In particular, 3-phase systems according to the invention are stabilized by surface active particles or molecules, such as for instance colloidal particles. The 3-phase systems of the invention can include a variety of other compounds, and can among others be used in pharmaceutical- or food-based applications. In particular, a 3-phase system according to the invention, such as for example an antibubble, may deliver pharmaceutical compounds.