FGF2 Aptamer Formulation Stability via Mannitol
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Solution Overview
Problem
Current pharmaceutical preparations containing aptamers, such as those for FGF2, face challenges in maintaining the stability and activity of the aptamer over a long term, particularly when stored in formulations like phosphate buffered saline (PBS), leading to multimerization and loss of binding activity.
Innovation Solution
A stable aqueous liquid formulation for FGF2 aptamer preparations is developed, using a solvent free of inorganic salts and incorporating a non-electrolyte osmoregulator like mannitol to maintain the aptamer as a monomer, ensuring stability and activity retention during storage and administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If phosphate buffered saline (PBS) or conventional electrolyte-containing formulations are used, then the preparation resembles existing aptamer products like Macugen, but the aptamer undergoes multimerization and loses binding activity over time
Solution Approach 1:
The invention removes inorganic salts (electrolytes) from the formulation by using water for injections as the solvent. This extraction of the harmful electrolyte component prevents multimerization while maintaining aptamer activity, directly resolving the contradiction between stability and activity.
Solution Approach 2:
The invention changes the formulation parameters by eliminating electrolytes and adjusting osmolarity using non-electrolyte osmoregulators (mannitol 1-10% w/v). This parameter change transforms the chemical environment to prevent multimerization while preserving binding activity.
2Duration of action of stationary object
If the aptamer is stored in aqueous formulation at 4°C, then long-term storage is enabled, but multimerization occurs leading to loss of activity
Solution Approach 1:
By removing electrolytes from the aqueous formulation, the invention eliminates the cause of multimerization that occurs during storage. This allows long-term storage at 4°C while maintaining aptamer activity, resolving the contradiction between storage duration and activity retention.
Solution Approach 2:
The invention introduces non-electrolyte osmoregulators (mannitol) as intermediary substances that maintain osmolarity without causing multimerization. These intermediaries enable long-term stable storage while preserving binding activity.
3Adaptability or versatility
If electrolyte-containing formulations are used to maintain physiological compatibility, then the preparation is suitable for injection, but the aptamer forms multimers and loses function
Solution Approach 1:
The invention extracts electrolytes from the formulation while maintaining injection compatibility through non-electrolyte osmoregulators. This resolves the contradiction by eliminating the harmful electrolyte component while preserving the essential property of injectability.
Solution Approach 2:
The invention changes the osmolarity adjustment strategy from electrolyte-based to non-electrolyte-based (mannitol). This parameter change maintains physiological compatibility for injection while preventing multimerization and preserving aptamer activity.
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 formulation effectively maintains the FGF2 aptamer in a monomeric state for at least 70% after 3 months at 4°C, preserving its binding activity and stability, allowing for long-term storage and effective administration as an aqueous injection.
Implementation Method 1
incorporating a non-electrolyte osmoregulator like mannitol to maintain the aptamer as a monomer
Data Source
AI summary
The present invention provides a preparation formulation capable of stably maintaining the activity of an aptamer, particularly an aptamer for FGF2, for a long term, thereby providing a pharmaceutical preparation containing an aptamer, particularly an FGF2 aptamer, as an active ingredient.