Lipid Microbubble Lyophilized Composition for Stable Ultrasound Contrast
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Solution Overview
Problem
The existing ultrasound contrast agent, Sonovue, suffers from poor stability of microbubbles after reconstitution, leading to a decrease in volume concentration over time, and inadequate pressure resistance, limiting its application to high-frequency probes and organs like the thyroid and mammary gland.
Innovation Solution
A lyophilized powder composition comprising distearoylphosphatidylcholine (DSPC), 1,2-dipalmitoylphosphatidylglycerol sodium (DPPG-Na), poly(ethylene glycol) 4000 (PEG4000), and palmitic acid, with a specific formulation and activation process, forms microbubbles with high volume concentration, good acoustic response, and improved pressure resistance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If conventional Sonovue microbubble formulation is used, then the contrast agent can be reconstituted and used for ultrasound imaging, but the microbubble stability deteriorates over time with gradual decrease in volume concentration
Solution Approach 1:
The patent modifies the chemical composition parameters of the microbubble shell by incorporating specific lipid ratios (DSPC:DPPG-Na:PEG4000:palmitic acid = 1:1:150-200:0.1-0.3) and activation conditions (37-42°C for 12-24 hours), which changes the physical-chemical properties to enhance microbubble stability and maintain volume concentration over time
Solution Approach 2:
The patent uses a composite lipid shell structure combining multiple components (DSPC, DPPG-Na, PEG4000, and palmitic acid) to create a microbubble membrane with improved mechanical strength and stability, preventing rapid dissolution and maintaining microbubble integrity in the bloodstream
2Reliability
If conventional Sonovue microbubbles are used with high-frequency probes, then the probe can detect signals, but the microbubbles rupture easily under high pressure reducing residence time and contrast effect
Solution Approach 1:
The patent changes the mechanical properties of the microbubble shell by adjusting lipid composition and activation parameters, creating a more robust microbubble structure that can withstand high-pressure environments from high-frequency probes (above 10 MHz) without premature rupture, thereby extending residence time in target organs
Solution Approach 2:
The patent optimizes the spherical geometry and surface tension characteristics of microbubbles through controlled formation and activation, creating a more stable curved structure that resists pressure-induced deformation and rupture under high-frequency ultrasound conditions
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 new composition maintains high stability and volume concentration of microbubbles, enhances acoustic response, and improves pressure resistance, suitable for various organs and probe frequencies, including high-frequency probes.
Implementation Method 1
a lyophilized powder composition for the preparation of a lipid microbubble ultrasonic contrast agent
Implementation Method 2
introducing a physiologically acceptable gas to the vial and sealing the vial
Implementation Method 3
can cause strong scattering of blood after being injected into the peripheral vein, which can significantly enhance the ultrasonic medical detection signal
Implementation Method 4
the particle size of ultrasound contrast agent microbubbles is correlated with the resonance frequency, and the higher the volume concentration of the central particle size within a certain range, the stronger its resonance frequency, i.e., the stronger the reflected acoustic signal
Data Source
AI summary
Provided are a lipid microbubble lyophilized powder composition and a preparation method therefor. The composition comprises 1 part by weight of distearoylphosphatidylcholine, 1 part by weight of sodium 1,2-palmitoylphosphatidylglycerol, 100-240 parts by weight of polyethylene glycol 4000, and 0.1-0.3 parts by weight of palmitic acid. The lyophilized powder composition and a physiologically acceptable gas form a sealed vial. The lyophilized powder composition is used for ultrasonic contrast after reconstitution. By adjusting the proportion of each component of the lipid microbubble lyophilized powder composition and process parameters, the lipid microbubble lyophilized powder composition is made to have the advantages of a narrow particle size distribution of reconstituted microbubbles, high microbubble stability, being less likely to crack, good pressure resistance, etc. During ultrasonic contrast, the composition can achieve stronger image acoustic signals and stay longer at the target part.