Viral Particle Stabilization via Amorphous Solid Matrix
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Solution Overview
Problem
Current methods for stabilizing viral particles during storage and transportation, such as refrigeration and freeze-drying, are costly, inconvenient, and can lead to reduced efficacy due to temperature fluctuations and stress-induced denaturation of proteins, especially in developing countries where refrigerated transport may not be available.
Innovation Solution
A method involving an aqueous solution of viral particles with N,N-dimethylglycine or N,N,N-trimethylglycine, methylsulfonylmethane, and sucrose or raffinose, followed by freeze-drying, which forms a stable amorphous solid matrix that protects viral activity against thermal and desiccation stresses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If refrigeration is used for storage and transportation, then viral particle stability is improved, but cost and convenience deteriorate due to expensive refrigerated transportation and storage infrastructure
Solution Approach 1:
The invention changes the storage temperature parameter from refrigerated (2-8°C) to frozen (-20°C or lower), and combines it with freeze-drying to create a stable solid matrix. This parameter change allows viral particles to be stored and transported without expensive refrigeration infrastructure, significantly improving ease of operation while maintaining viral particle stability through the protective amorphous solid matrix formed by sugars and polyols
Solution Approach 2:
The invention uses composite materials consisting of viral particles combined with sugars (sucrose, raffinose, trehalose) and polyols (methylsulfonylmethane, glycerol, ethylene glycol) to form an amorphous solid matrix through freeze-drying. This composite structure provides both the stability needed for long-term storage and the convenience of room temperature storage and transportation, resolving the contradiction between reliability and ease of operation
2Ease of operation
If freeze-drying is used for preservation, then storage convenience is improved, but viral particle stability deteriorates due to stress-induced denaturation of proteins
Solution Approach 1:
The invention applies beforehand cushioning by incorporating sugars and polyols into the viral particle solution before freeze-drying. These compounds form a protective amorphous solid matrix that cushions and protects viral particles from the denaturing stresses of freezing and drying, preventing protein unfolding and maintaining viral particle stability while enabling convenient frozen storage
Solution Approach 2:
The invention optimizes parameters including sugar concentration (10-500 mM), polyol concentration (10-500 mM), pH (6.0-8.0), and freezing temperature (-20°C or lower) to create conditions where the amorphous solid matrix forms effectively during freeze-drying. These parameter changes ensure both viral particle stability and storage convenience are achieved simultaneously
3Loss of time
If conventional stabilizers are used during freeze-drying, then processing time is reduced, but viral particle stability deteriorates due to insufficient protection against denaturation
Solution Approach 1:
The invention uses composite materials combining multiple sugars (sucrose, raffinose, trehalose) and polyols (methylsulfonylmethane, glycerol, ethylene glycol) in specific concentrations. This composite formulation provides superior protection against denaturation during freeze-drying compared to conventional single stabilizers, maintaining viral particle stability while enabling efficient processing with appropriate drying cycles
Solution Approach 2:
The invention optimizes concentration parameters of sugars (10-500 mM) and polyols (10-500 mM) to achieve effective stabilization during freeze-drying. These parameter optimizations ensure adequate protection against denaturation while allowing for practical processing times through controlled drying cycles that remove water without exposing viral particles to prolonged denaturing 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
This approach maintains viral activity and structure during freeze-drying and long-term storage, allowing for stable preservation and extended shelf life without the need for refrigeration, thus facilitating easier transportation and storage.
Implementation Method 1
a method involving an aqueous solution of viral particles with N,N-dimethylglycine or N,N,N-trimethylglycine, methylsulfonylmethane, and sucrose or raffinose, followed by freeze-drying
Implementation Method 2
forms a stable amorphous solid matrix that protects viral activity against thermal and desiccation stresses
Data Source
Figure 1
Figure 2A~2B
Figure 3
AI summary
A method for preserving viral particles comprising: (a) providing an aqueous solution of (i) viral particles, (ii) one or more sugars, and (iii) a compound of formula (I) or a physiologically acceptable salt or ester thereof; and (b) drying the solution to form a composition incorporating said viral particles.