BPA Pharmaceutical Composition Stabilization via 2-Hydroxy Amine Complexation
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Solution Overview
Problem
Boronophenylalanine (BPA) has poor aqueous solubility at physiological pH, leading to large volume injections and poor stability of BPA fructose complexes, which limits their practical application in boron neutron capture therapy (BNCT).
Innovation Solution
A pharmaceutical composition comprising BPA or its pharmaceutically acceptable salt and a 2-hydroxy amine compound (2HA), such as those represented by formulas I and II, which enhances the aqueous solubility of BPA and stabilizes it at physiological pH, allowing for a dry powder formulation that can be easily reconstituted to a high-concentration aqueous solution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If BPA is solubilized with strong acid or strong base to improve aqueous solubility, then solubility is improved, but stability and safety are compromised
Solution Approach 1:
The patent introduces amino acids as intermediary substances that form soluble complexes with BPA at physiological pH. These amino acids act as mediators between BPA and water, enabling solubility without requiring extreme pH conditions. The amino acid-BPA complex serves as an intermediate form that is both soluble and stable, resolving the contradiction between solubility improvement and stability maintenance.
2Quantity of substance
If BPA fructose complex is used to improve solubility, then some solubility enhancement is achieved, but the solution volume becomes excessively large requiring long infusion time
Solution Approach 1:
The patent changes the chemical parameters of the solubilizing agent from saccharides to amino acids, which have different molecular weights and complexation properties. This parameter change results in a more compact complex structure that achieves the same solubility enhancement with a smaller solution volume, thereby reducing infusion time while maintaining BPA solubility.
3Volume of moving object
If BPA fructose complex is freeze-dried to reduce storage volume, then storage convenience is improved, but dissolution rate becomes extremely low
Solution Approach 1:
The patent creates a composite material system consisting of BPA complexed with amino acids. This composite has different physical and chemical properties compared to the BPA-fructose complex, including better preservation of dissolution characteristics after freeze-drying. The amino acid-BPA composite structure maintains porosity and surface area properties that facilitate rapid dissolution even in freeze-dried form, resolving the contradiction between reduced storage volume and maintained dissolution rate.
4Quantity of substance
If BPA fructose complex is used, then initial solubility is improved, but shelf life is only a few days due to poor stability
Solution Approach 1:
The patent effectively replaces the unstable BPA-fructose complex with a more stable BPA-amino acid complex. The amino acids, being naturally occurring and biocompatible, provide a more stable complexation environment that extends shelf life significantly. This substitution transforms a short-lived formulation into a long-term stable formulation suitable for extended storage and clinical use.
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 achieves high concentration aqueous solutions of BPA, reducing infusion volume and time, and provides improved stability and ease of administration, making it suitable for BNCT.
Implementation Method 1
A pharmaceutical composition is disclosed. The pharmaceutical composition may comprise boronophenylalanine (BPA) or a pharmaceutically acceptable salt thereof and a 2-hydroxy amine compound (2HA) or a pharmaceutically acceptable salt thereof
Data Source
AI summary
A pharmaceutical composition is disclosed. The pharmaceutical composition may comprise boronophenylalanine (BPA) or a pharmaceutically acceptable salt thereof and a 2-hydroxy amine compound (2HA) or a pharmaceutically acceptable salt thereof.