Crystalline Fosfomycin Amino Acid Salts for Low-Sodium Injection
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Solution Overview
Problem
Existing fosfomycin compositions, particularly disodium salt, pose risks for patients with cardiovascular and renal issues due to high sodium content and low solubility, limiting their use in certain patient groups and affecting bioavailability.
Innovation Solution
Development of crystalline amino acid salts of fosfomycin, specifically lysine and histidine salts, which are more suitable for parenteral administration, offering improved solubility and reduced sodium intake.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If disodium fosfomycin salt is used for parenteral administration, then fosfomycin can be effectively administered, but high sodium load causes electrolyte imbalances and is contraindicated in patients with cardiovascular and renal pathologies
Solution Approach 1:
The patent changes the cation parameter of the fosfomycin salt from sodium to amino acids (lysine, histidine, arginine). This substitution fundamentally alters the electrolyte profile while maintaining fosfomycin's therapeutic effectiveness, directly resolving the contradiction between effective administration and harmful sodium load
Solution Approach 2:
Amino acids serve as intermediary substances that replace sodium as the counterion for fosfomycin. These intermediaries provide the necessary salt form for parenteral administration without introducing harmful electrolyte effects, enabling effective drug delivery while avoiding the original harmful factor
2Object-affected harmful factors
If calcium fosfomycin salt is used, then sodium load is reduced, but low solubility results in low bioavailability
Solution Approach 1:
The patent changes the cation parameter from calcium to specific amino acids (lysine, histidine, arginine), which fundamentally alters the solubility characteristics. These amino acid salts exhibit optimal solubility parameters for parenteral administration while maintaining low sodium load, simultaneously resolving both the harmful factor reduction and bioavailability requirements
3Ease of operation
If fosfomycin is formulated as disodium salt for intravenous use, then it can be administered parenterally, but high sodium content limits use in elderly and patients with cardiovascular or renal diseases
Solution Approach 1:
The patent changes the electrolyte parameter by substituting sodium ions with amino acid cations. This parameter change maintains the parenteral administration capability while expanding adaptability to include elderly patients and those with cardiovascular or renal diseases who cannot tolerate high sodium loads
Solution Approach 2:
The amino acid salts of fosfomycin provide multi-functionality by serving as both the therapeutic agent and the electrolyte source. The amino acids themselves have physiological benefits and do not produce harmful electrolyte effects, making the formulation universally suitable across different patient populations including those with cardiovascular and renal pathologies
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 crystalline lysine and histidine salts provide enhanced solubility and bioavailability, making them suitable for patients with cardiovascular and renal issues, and demonstrate higher concentration in urine compared to disodium salt.
Implementation Method 1
The crystalline lysine and histidine salts of the present invention show physicochemical properties (solubility, ions uptake, pH) which are more adequate for parenteral administration
Data Source
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AI summary
It refers to pharmaceutical or veterinary composition which comprises a therapeutically effective amount of a crystalline form of an amino acid salt of fosfomycin, together with one or more pharmaceutically or veterinary acceptable excipients, wherein the amino acid is lysine or histidine. It also refers to processes for the preparation of such crystalline forms and to the use of the same in injectable preparations for parenteral administration.