Thermoreversible Adjuvant Emulsion via Phase Inversion
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing vaccine formulations require high-energy shear technologies for adjuvant emulsion production, which are complex, costly, and may lead to thermal denaturation of components, while also being less effective in inducing immune responses and requiring higher antigen doses.
Innovation Solution
A thermoreversible oil-in-water adjuvant emulsion is developed using a phase inversion temperature process, comprising squalene, polyoxyethylene alkyl ether hydrophilic nonionic surfactant, and hydrophobic nonionic surfactants, allowing for the production of monodisperse droplets <200 nm in size, enhancing stability and immune response with reduced antigen doses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If high-pressure homogenizer (microfluidizer) is used to produce adjuvant emulsion, then oil droplet size can be reduced to 100-1000 nm range, but the process requires high mechanical energy and complex shear technology
Solution Approach 1:
The patent applies phase inversion temperature (PIT) process where the emulsion system transitions between oil-in-water and water-in-oil phases by controlling temperature. This phase transition mechanism naturally generates fine emulsion droplets without requiring high-shear mechanical devices, thus resolving the contradiction between achieving small droplet size and avoiding complex equipment
Solution Approach 2:
The patent replaces the mechanical high-shear homogenization system with a thermal phase inversion system. Instead of using mechanical energy to create and maintain small droplets, the invention uses temperature-controlled phase transitions to achieve the same emulsification effect, eliminating the need for complex shear technology equipment
2Volume of moving object
If high mechanical energy is applied to reduce oil droplet size, then emulsion can be obtained with mean droplet size around 170-500 nm, but thermal denaturation of components may occur
Solution Approach 1:
The PIT process utilizes controlled phase transitions at moderate temperatures to achieve emulsification. The system passes through an inverted micellar phase during temperature cycling, which naturally produces fine droplets without requiring the high mechanical energy that causes thermal denaturation
Solution Approach 2:
By substituting mechanical energy input with thermal phase transition control, the invention avoids the high-shear conditions that generate excessive heat and mechanical stress on sensitive vaccine components, thereby preventing thermal denaturation while still achieving small droplet sizes
3Reliability
If conventional adjuvant formulations are used, then vaccine production is established, but immune response is insufficient and higher antigen doses are required
Solution Approach 1:
The phase inversion process creates a unique emulsion structure with narrow droplet size distribution and optimized interfacial properties. This structured emulsion enhances antigen delivery and immune cell uptake efficiency, allowing for reduced antigen doses while maintaining or improving immune response, thus resolving the contradiction between production reliability and antigen quantity requirements
4Ease of manufacture
If high-shear emulsion process is used, then adjuvant formulation can be produced, but the process is costly and less effective in inducing immune responses
Solution Approach 1:
The patent employs phase inversion temperature methodology that can be implemented using simple heating and cooling equipment rather than expensive high-shear homogenizers. This approach maintains ease of manufacture while producing superior emulsion quality that enhances immune response efficiency, effectively resolving the contradiction between manufacturing simplicity and immunogenicity
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 process simplifies vaccine production, increases immune response efficacy, reduces antigen doses, and maintains stability during lyophilization, making it suitable for various vaccine antigens like flu and cytomegalovirus, while ensuring safety and cost-effectiveness.
Implementation Method 1
the emulsion is obtained by means of a phase inversion temperature process
Implementation Method 2
wherein the emulsion is thermoreversible
Data Source
AI summary
The invention relates to an oil-in-water adjuvant emulsion which comprises at least:squalene,an aqueous solvent,a polyoxyethylene alkyl ether nonionic surfactant,a hydrophobic nonionic surfactant,which emulsion is thermoreversible, and wherein 90% of the population by volume of the oil drops has a size less than 200 nm.The invention also relates to a process for preparing an immunogenic composition according to which at least one vaccine antigen is mixed with an oil-in-water emulsion, wherein the oil-in-water emulsion is obtained by means of a temperature-variation phase-inversion process.