Vancomycin Solutions Stabilized by N-Acetyl-D-Amino Acids
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Solution Overview
Problem
Existing liquid formulations of Vancomycin hydrochloride and related glycopeptide antibiotics suffer from limited stability, making them impractical for long-term use and storage, and there is a need for solutions that maintain stability under normal conditions for extended periods without refrigeration.
Innovation Solution
Incorporating N-acetyl-D-amino acids, such as N-acetyl-D-Alanine or N-acetyl-Glycine, into aqueous solutions of glycopeptide antibiotics, along with optional amino acids like Lysine, at specific pH ranges (2-7, preferably 4-5.5) and solvent concentrations, stabilizes the antibiotics, allowing for long-term storage and use without refrigeration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid formulations of Vancomycin hydrochloride are prepared for parenteral use, then the antibiotic is readily available for administration, but the stability of the Vancomycin hydrochloride in the aqueous solution is limited
Solution Approach 1:
The patent applies preliminary action by pre-formulating Vancomycin hydrochloride in liquid solutions with stabilizing agents (amino acids, peptides, or proteins) before use. This preliminary stabilization prevents degradation during storage, allowing the medication to be ready for immediate administration without requiring freezing or freeze-drying while maintaining stability for extended periods at controlled temperatures.
2Stability of the object's composition
If Vancomycin is stored as a dry solid or frozen liquid preparation, then stability is maintained, but the complexity of storage and administration increases
Solution Approach 1:
The patent applies parameter changes by modifying the chemical environment of Vancomycin hydrochloride through the addition of stabilizing agents (amino acids, peptides, or proteins) and adjusting pH levels. These parameter changes transform the formulation from an unstable aqueous solution requiring freezing into a stable liquid preparation that can be stored at controlled temperatures (2-8°C or up to 25°C) without degradation, simplifying both storage and administration.
3Stability of the object's composition
If stabilizing agents are added to Vancomycin solutions, then stability is improved, but the composition becomes more complex
Solution Approach 1:
The patent applies the intermediary principle by introducing amino acids, peptides, or proteins as mediating substances that protect Vancomycin hydrochloride from degradation. These intermediaries act as stabilizing agents that interact with the antibiotic to prevent hydrolysis and degradation, while being pharmaceutically acceptable and compatible with the therapeutic application, thus improving stability without significantly complicating the formulation.
Data Source
AI summary
Solutions comprising a glycopeptide antibiotic, for example Vancomycin, and an amino acid or amino acid derivative such as an N-acetyl amino acid are provided. These solutions are stable or stabilized for long-term periods at conditions of normal use and storage, and can be formulated as pharmaceutical solutions for use in subjects. Methods of manufacturing and using these solutions are also provided, as are methods of stabilizing a glycopeptide antibiotic, for example Vancomycin, using amino acids or amino acid derivatives such as N-acetyl amino acids.