Glassy Matrix Stabilizing Composition for Biological Materials
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Solution Overview
Problem
Current methods for preserving biological materials, such as freeze-drying, often result in damage due to ice crystal formation and high drying temperatures, leading to instability and loss of activity, especially at high temperatures and humid environments, and existing cryoprotectants like trehalose have limitations in penetrating cells and providing long-term storage stability.
Innovation Solution
A composition of carbohydrates (di-, oligo-, and polysaccharides) and glass-enhancing compounds like citric acid, combined with proteins or protein hydrolysates, is used to create a stable glassy structure during drying, which protects biological materials by embedding them in a glassy matrix, preventing denaturation and maintaining activity under harsh conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If freeze-drying is used to preserve biological materials, then the materials can be stored in a dry state, but ice crystal formation during freezing causes damage and loss of activity
Solution Approach 1:
The patent applies preliminary freezing at controlled rates to form a glassy matrix structure before final drying. This preliminary action creates a protective amorphous structure that prevents ice crystal formation during subsequent storage, thereby protecting biological materials from ice crystal damage while maintaining storage stability
Solution Approach 2:
The patent changes the physical state parameters by controlling freezing and drying conditions to form a glassy (amorphous) state rather than crystalline ice. By adjusting temperature and humidity parameters during processing, the material transitions to a glassy matrix that protects biological components without forming damaging ice crystals
2Object-affected harmful factors
If high concentrations of trehalose are used as cryoprotectant, then protection during freezing is enhanced, but penetration into cells is inadequate and storage stability at high temperatures is not achieved
Solution Approach 1:
The patent uses a composite formulation combining multiple sugars (including trehalose, sucrose, and other carbohydrates) with proteins or protein hydrolysates. This composite material provides both freezing protection through the sugar glass matrix and enhanced high-temperature storage stability through the protein components, overcoming the limitations of trehalose alone
Solution Approach 2:
The patent creates different functional zones within the formulation: the sugar components provide freezing protection and glassy matrix formation, while the protein components specifically address high-temperature stability. This local differentiation of protective functions allows the formulation to address multiple storage challenges simultaneously
3Ease of manufacture
If ambient air-drying or vacuum-drying at ambient temperatures is used, then drying is simpler, but high drying temperatures cause significant damage to bioactive materials
Solution Approach 1:
The patent utilizes phase transition from frozen to dried state through controlled sublimation and evaporation. By freezing the formulation first and then removing water in a controlled manner, the process avoids high-temperature damage while maintaining simplicity, as the material is already in a frozen state that protects bioactives during water removal
4Reliability
If water is present in the environment during storage, then the glassy matrix becomes plasticized and transitions to rubbery or plastic state, but this reduces physical stability and increases chemical reactivity
Solution Approach 1:
The patent uses the glassy matrix formed by sugars and proteins as an intermediary barrier between the biological materials and the external environment. This glassy state acts as a protective medium that prevents direct interaction between water and the bioactives, maintaining both physical and chemical stability even when exposed to humid environments
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 method provides a cost-effective and scalable way to preserve sensitive bioactive materials, maintaining significant activity and stability over extended periods at elevated temperatures and varying humidity, avoiding the limitations of traditional cryoprotectants and drying methods.
Implementation Method 1
A composition of carbohydrates (di-, oligo-, and polysaccharides) and glass-enhancing compounds like citric acid, combined with proteins or protein hydrolysates, is used to create a stable glassy structure during drying, which protects biological materials by embedding them in a glassy matrix
Implementation Method 2
freeze-drying has traditionally been the most common method
Implementation Method 3
Freeze-drying combines the stresses due to both freezing and drying
Data Source
AI summary
The present invention includes compositions and drying methods for preserving sensitive bioactive materials, such as peptides, proteins, hormones, nucleic acids, antibodies, drugs vaccines, yeast, bacteria (probiotic or otherwise), viruses and/or cell suspensions, in storage. The compositions include a carbohydrates component and a glass enhancer component, wherein the carbohydrate component includes a mixture of di-, oligo- and polysaccharides and the glass enhancer includes ions of organic acid and protein hydrolysates. The composition is prepared by dispersing all the solid components in a solution and then snap-frozen to form small beads, strings or droplets. The preferred drying method of the frozen beads, strings or droplets is initiated by a short purging and structure stabilizing step of the frozen particles under a vacuum pressure of less than <2000 mTORR followed by a primary drying step under vacuum pressure of more than >2000 mTORR and at a desired temperature. During the secondary and final drying step of the material a full vacuum pressure and elevated temperature are applied, to achieve a final desirable water activity of the dry material.