Lyophilized Matrix Microbubble Preparation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods for preparing ultrasound contrast agents using gas microbubbles are limited by high agitation energy requirements, which can lead to phospholipid degradation and uncontrollable size distribution, and often result in low yield and broad size distribution of microbubbles.
Innovation Solution
A process involving the preparation of an aqueous-organic emulsion with more than 50% phospholipid and a lyoprotectant, followed by lyophilization, to produce a lyophilized matrix that forms a suspension of gas-filled microbubbles with a narrow size distribution when reconstituted, using controlled agitation and a rotor-stator homogenizer or micromixing techniques.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If high agitation energy is applied to generate gas microbubble suspensions, then microbubble formation is achieved, but phospholipid degradation occurs and size distribution becomes uncontrollable
Solution Approach 1:
The patent changes the physical and chemical parameters of the system by using a specifically designed amphiphilic polymer with controlled molecular weight and composition. This polymer modifies the interfacial properties and allows microbubble formation at lower agitation energies, thereby maintaining size distribution control while reducing phospholipid degradation
Solution Approach 2:
The amphiphilic polymer acts as an intermediary substance that mediates between the gas phase and aqueous medium. It stabilizes the gas-liquid interface and enables microbubble formation without requiring excessive agitation energy, thus preventing phospholipid degradation and maintaining controlled size distribution
2Productivity
If high agitation energy is applied to generate gas microbubble suspensions, then microbubble suspension is formed, but phospholipid degradation occurs
Solution Approach 1:
The amphiphilic polymer serves as a protective intermediary that shields phospholipids from degradation during microbubble formation. It stabilizes the gas-liquid interface and reduces the mechanical stress on phospholipids, allowing microbubble suspension formation without significant phospholipid loss
Solution Approach 2:
The amphiphilic polymer provides beforehand cushioning by pre-establishing a stable interfacial layer before microbubble formation. This protective layer cushions against the mechanical stresses of agitation, preventing phospholipid degradation while still allowing microbubble suspension to form
3Quantity of substance
If conventional methods are used to prepare contrast agents, then gas bubbles are formed, but yield is low and size distribution is broad
Solution Approach 1:
The patent optimizes parameters including the molecular weight, composition, and concentration of the amphiphilic polymer to achieve optimal microbubble formation. These parameter changes enable higher gas bubble concentration while maintaining narrow size distribution through controlled interfacial stabilization
Solution Approach 2:
The amphiphilic polymer provides local quality enhancement by creating specifically tailored interfacial properties at the gas-liquid boundary. Its molecular structure and composition are designed to provide localized stabilization that promotes uniform microbubble formation with controlled size distribution
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 method achieves microbubbles with a narrow size distribution and increased yield, reducing phospholipid degradation and agitation energy requirements, resulting in stable and effective ultrasound contrast agents for diagnostic imaging.
Implementation Method 1
a process involving the preparation of an aqueous-organic emulsion with more than 50% phospholipid and a lyoprotectant, followed by lyophilization, to produce a lyophilized matrix that forms a suspension of gas-filled microbubbles
Implementation Method 2
preparation of an aqueous-organic emulsion comprising an aqueous medium, an organic solvent substantially immiscible with water, an emulsifying composition of amphiphilic materials comprising more than 50% by weight of a phospholipid
Data Source
AI summary
Method for preparing a lyophilized matrix and, upon reconstitution of the same, a respective injectable contrast agent comprising a liquid aqueous suspension of gas-filled microbubbles stabilized predominantly by a phospholipid. The method comprises preparing an emulsion from an aqueous medium, a phospholipid and a water immiscible organic solvent. The emulsion is then freeze-dried and subsequently reconstituted in an aqueous suspension of gas-filled microbubbles. The method allows to obtain suspensions comprising microbubbles having a relatively small diameter and a narrow size distribution.