Magnetic Microbubble Composition for Stable Targeted Ultrasound Delivery

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing magnetic microbubble ultrasound contrast agents have poor stability and fail to meet the requirements for in vivo cyclic targeted drug delivery, especially in high flow rate areas, due to insufficient cavitation threshold and stability.

Innovation Solution

A composition for magnetic ultrasound contrast agents is developed, incorporating specific ratios of poloxamer and sodium citrate as surfactants to enhance the stability and cavitation threshold, comprising lipids, surfactants, and magnetic nanoparticles, with a core-shell structure and positive charge modification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If magnetic particles are coated with a hydrophobic substance to enable attachment to gas bubbles, then the magnetic ultrasound contrast agent can be formed, but the magnetic particles aggregate due to hydrophobic interaction

Engineering Contradiction:
Improveattachment capabilityVSAvoidmagnetic particle dispersion
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent introduces a hydrophilic polymer coating as an intermediary layer between the hydrophobic magnetic particles and the aqueous medium. This coating has dual functionality: its hydrophobic segments interact with the magnetic particles while its hydrophilic segments interact with water, preventing aggregation while maintaining attachment capability to gas bubbles.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite structure where magnetic particles are coated with hydrophobic substance and further covered with hydrophilic polymer. This multi-layer composite material combines the magnetic properties of the particles with the dispersibility of the hydrophilic polymer, resolving the contradiction between attachment capability and dispersion stability.

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If the concentration of magnetic particles is increased to enhance ultrasound signal, then the contrast enhancement improves, but the aggregation of magnetic particles increases

Engineering Contradiction:
Improveultrasound signal detectionVSAvoidmagnetic particle dispersion
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The hydrophilic polymer coating acts as a spacer and stabilizer that prevents magnetic particle aggregation even at high concentrations. By providing steric hindrance and hydrophilic interaction with the aqueous medium, it allows higher particle concentrations to be achieved without aggregation, thereby enhancing ultrasound signal while maintaining dispersion.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If a hydrophobic substance is used to coat magnetic particles for gas bubble attachment, then contrast agent formation is enabled, but blood compatibility is reduced

Engineering Contradiction:
Improvecontrast agent formationVSAvoidblood compatibility
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent creates a composite coating structure where the inner layer is hydrophobic (for magnetic particle attachment) and the outer layer is hydrophilic (for blood compatibility). This composite structure allows the contrast agent to maintain its formation capability while the hydrophilic outer layer prevents adverse reactions with blood components.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

Different regions of the coating have different properties: the inner region near the magnetic particle is hydrophobic for strong attachment, while the outer region facing the aqueous environment and blood is hydrophilic for compatibility. This spatial variation in properties resolves the contradiction between contrast agent formation and blood compatibility.

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

The improved stability and cavitation threshold enable targeted drug delivery with enhanced local concentration and response, maintaining stability in high flow rate conditions.

Implementation Method 1

ultrasound contrast agents based on microbubbles that exploit the phenomenon of acoustic cavitation

Methodology Applied
Scientific EffectAcoustic cavitation: Acoustic Cavitation

Implementation Method 2

magnetic microbubble ultrasound contrast agent

Methodology Applied
Scientific EffectMagnetic field interaction: Magnetic Field

Data Source

PatentEP4046659B1Magnetic ultrasound contrast agent composition, magnetic ultrasound contrast agent, and magnetic microbubble ultrasound contrast agent and preparation method therefor
Publication Date: 2026.05.06 NANJING TRANSCEND VIVOSCOPE BIO TECH CO LTD
  • EP4046659B1 patent drawingFigure 1
  • EP4046659B1 patent drawingFigure 2(a)~2(b)

AI summary

The invention relates to the field of biological medicines, and particularly relates to a composition for magnetic ultrasound contrast agent, a magnetic ultrasound contrast agent, a magnetic microbubble ultrasound contrast agent, and a preparation method thereof. The composition for magnetic ultrasound contrast agent includes a lipid, a surfactant and a magnetic nanoparticle; the surfactant consists of a surfactant A and a surfactant B, the surfactant A is in a free state, and the surfactant B is in a bonding state and is modified on the surface of the magnetic nanoparticle; the HLB value of the surfactant A is greater than 8. The magnetic microbubble ultrasound contrast agent obtained from the composition for magnetic ultrasound contrast agent has higher stability and may meet requirements for in vivo cyclic targeted delivery, thereby achieving the local high-concentration targeted delivery of a medication.