Virus Storage via Tromethamine-Cyclodextrin Buffer
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Solution Overview
Problem
Existing methods for preserving virus infectivity, such as freezing with cryo-protectants, can damage viruses and are not entirely effective, particularly for intra-tracheal and intra-pulmonary administration due to irritant effects of glycerol and do not completely eliminate freezing damage.
Innovation Solution
A composition comprising infectious viral particles, tromethamine, cyclodextrin, and optional cryoprotectants like glycerol or sucrose, which maintains virus infectivity by using a pH-dependent buffer system that binds and releases viruses from cyclodextrin during storage, allowing for long-term preservation without freezing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If freezing is used to preserve virus infectivity, then virus storage duration is extended, but virus damage increases and infectivity is reduced
Solution Approach 1:
The patent changes the temperature parameter from frozen state to refrigerated state (2°C to 8°C), and modifies the chemical composition by using tromethamine buffer with cyclodextrin instead of traditional glycerol-based cryoprotectants. This parameter change allows the virus to be stored without freezing while maintaining infectivity.
Solution Approach 2:
The patent extracts the freezing step from the storage process entirely. By removing the need for freezing and using only refrigeration with the specialized buffer system, the method eliminates freeze-thaw damage while preserving virus infectivity over extended periods.
2Reliability
If glycerol is used as a cryoprotectant, then freezing damage is reduced, but pulmonary epithelium irritation occurs
Solution Approach 1:
The patent extracts glycerol from the formulation entirely, replacing it with tromethamine buffer and cyclodextrin. This removal eliminates the pulmonary irritation issue while maintaining virus protection capabilities through the alternative buffer system.
Solution Approach 2:
The patent uses tromethamine and cyclodextrin as safer, biocompatible alternatives to glycerol. These substances provide the necessary buffer and protection functions without the harmful side effects, making them suitable for pulmonary administration.
3Duration of action of stationary object
If traditional cryopreservation methods are used, then virus storage is achieved, but freezing damage is not completely eliminated
Solution Approach 1:
The patent changes the storage temperature parameter from frozen to refrigerated conditions, and modifies the chemical environment with tromethamine buffer and cyclodextrin. This creates optimal conditions that prevent freezing damage entirely while maintaining virus stability and infectivity.
Solution Approach 2:
The tromethamine buffer with cyclodextrin acts as an intermediary protective environment that shields the virus from damage during storage. This buffer system provides molecular protection without requiring freezing, eliminating freeze-thaw stress on the viral particles.
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 composition retains at least 70-95% of initial viral particle concentration and infectious titer for extended periods, including up to a year when stored as a non-frozen liquid, effectively addressing the limitations of traditional preservation methods.
Implementation Method 1
tromethamine able to change pH in response to change in temperature
Implementation Method 2
a pH-dependent buffer system that binds and releases viruses from cyclodextrin during storage
Data Source
AI summary
A temperature-responsive virus storage system that allows virus to be stored, such as a non-frozen liquid, and maintain infectivity is described.