Thermoreversible Immuno-adjuvant Emulsion via Phase Inversion
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Solution Overview
Problem
Existing influenza vaccines require complex and energy-intensive processes to produce stable adjuvant emulsions, which are not reproducible and scalable for large-scale production, and often require high doses of antigens while posing safety concerns.
Innovation Solution
A phase inversion process using squalene, polyoxyethylene alkyl ether, and hydrophobic nonionic surfactants to create a monodisperse oil-in-water emulsion with droplets less than 160 nm, allowing for a simpler, low-energy production method that is safe and scalable, and capable of reducing antigen doses while maintaining immune response effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If high pressure homogenizer (microfluidizer) is used to obtain small oil droplet size, then droplet size is reduced to 100-1000 nm, but the process requires high mechanical energies and complex shearing technology
Solution Approach 1:
The patent employs phase inversion temperature (PIT) methodology where the emulsion system undergoes phase transition at a specific temperature. By heating the mixture to the PIT and then cooling it, the system naturally inverts from water-in-oil to oil-in-water emulsion, producing monodisperse droplets of 100-1000 nm without requiring high-pressure homogenization or complex mechanical shearing devices.
2Stability of the object's composition
If complex high energy process is used to produce stable emulsion, then emulsion stability is improved, but manufacturing complexity and energy consumption increase
Solution Approach 1:
The patent utilizes phase inversion temperature (PIT) methodology where the emulsion system undergoes phase transition at a specific temperature. By heating the mixture to the PIT and then cooling it, the system naturally inverts from water-in-oil to oil-in-water emulsion, producing monodisperse droplets of 100-1000 nm without requiring high-pressure homogenization or complex mechanical shearing devices.
Solution Approach 2:
The patent systematically optimizes formulation parameters including surfactant ratios (HLB values), oil phase composition (squalene content), and temperature parameters to achieve phase inversion at a controlled temperature. This parameter optimization enables reproducible production of stable monodisperse emulsions through simple heating and cooling cycles.
3Reliability
If conventional adjuvant emulsion is used, then immune response is enhanced, but antigen dose must be high which raises safety concerns
Solution Approach 1:
The patent replaces the mechanical energy input system (high-pressure homogenizers) with a thermal energy system (heating and cooling cycles). This substitution enables the production of stable monodisperse emulsions that effectively adjuvant vaccines while using lower antigen doses, as the uniform droplet distribution and appropriate size range enhance antigen presentation to the immune system.
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 results in a stable, reproducible, and safe adjuvant emulsion that effectively enhances immune response with reduced antigen doses, suitable for large-scale production and storage, particularly beneficial for influenza vaccines.
Implementation Method 1
a polyoxyethylene alkyl ether, whose hydrophilic/lipophilic balance is greater than or equal to 10, a hydrophobic nonionic surfactant, whose hydrophilic/lipophilic balance is less than or equal to 9
Implementation Method 2
an oil-in-water adjuvant emulsion obtained by a phase inversion process by variation of the temperature
Data Source
AI summary
The invention relates to an oil-in-water adjuvant emulsion comprising at least: • squalene, • an aqueous solvent, • a nonionic surfactant which is a polyoxyethylene alkyl ether, • a hydrophobic, thermoreversible nonionic surfactant, in which 90% of the volume population of oil droplets has a size less than 200 nm. The invention also relates to a method for preparing an immunogenic composition in which at least one vaccine antigen is mixed with an oil-in-water emulsion, characterized in that the oil-in-water emulsion is obtained by a phase inversion process by temperature variation.