Thermally Treated Freeze-Dried Microvesicles for Pressure Stability

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Solution Overview

Problem

Existing methods for manufacturing gas-filled microvesicles, such as those used in contrast-enhanced ultrasound imaging, do not adequately stabilize the microbubbles, leading to insufficient resistance to pressure and persistence in the bloodstream.

Innovation Solution

A method involving the preparation of a freeze-dried composition comprising an amphiphilic material and a freeze-drying protecting component, followed by heating the freeze-dried product at controlled temperatures to enhance stability and resistance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional freeze-drying methods are used to manufacture gas-filled microvesicles, then the manufacturing process is simple and quick, but the microvesicles have insufficient resistance to pressure and persistence in the bloodstream

Engineering Contradiction:
Improveresistance to pressure and persistence in bloodstreamVSAvoidmanufacturing process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by incorporating a heating step immediately after freeze-drying while the product is still in the vial. This thermal treatment is performed before the product is removed from the freeze-dryer, allowing the heat to penetrate the porous structure and modify the stabilizing film properties in advance, thereby improving pressure resistance and bloodstream persistence without adding complex post-processing steps

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies parameter changes by introducing a controlled thermal parameter (heating at 25-40°C for 1-24 hours) after the freeze-drying process. This temperature parameter modification transforms the physical and chemical properties of the stabilizing film, enhancing the microvesicles' mechanical strength and stability without fundamentally changing the manufacturing equipment or process flow

Inventive Principle:
Principle #35Parameter changes

2Reliability

If a heating step is added to improve microvesicle stability, then resistance to pressure and persistence are enhanced, but the manufacturing time and process complexity increase

Engineering Contradiction:
Improvemicrovesicle stability and persistenceVSAvoidmanufacturing time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent applies merging by combining the heating step with the existing freeze-drying process sequence. The thermal treatment is integrated as a continuous operation within the same manufacturing workflow, eliminating the need for separate handling, packaging, and storage steps that would otherwise be required between freeze-drying and final product release, thereby minimizing additional time loss

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 method results in microvesicles with increased resistance to pressure, leading to improved persistence in the bloodstream and enhanced performance in ultrasound imaging and therapeutic applications.

Implementation Method 1

freeze-drying the liquid mixture to remove said solvent and obtain a freeze-dried solid product

Methodology Applied
Scientific EffectFreeze-drying: Freeze Drying

Implementation Method 2

heating the freeze-dried product at controlled temperatures to enhance stability and resistance

Methodology Applied
Scientific EffectHeating: Heating

Data Source

PatentUS12551446B2Freeze-dried product and gas-filled microvesicles suspension
Publication Date: 2026.02.17 BRACCO SUISSE SA

AI summary

A method of manufacturing a suspension of gas-filled microvesicles by reconstituting a freeze-dried product and a suspension obtained according to said method, where the freeze-dried product has been subjected to a thermal treatment.