Cysteine Injection Formulation Low Aluminum
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Solution Overview
Problem
Cysteine solutions used in neonatal total parenteral nutrition have low stability and high aluminum content, leading to oxidation to cystine and potential toxicity, necessitating improved formulations with reduced aluminum levels and extended stability.
Innovation Solution
Development of cysteine compositions with less than 400 μg/L aluminum, characterized by low pH and low dissolved oxygen content, devoid of visible particulate matter, and prepared using acidified water and nitrogen atmosphere to minimize oxidation, ensuring stability and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If cysteine is formulated in solution at typical pH levels (5-7), then the solution is stable for storage, but cysteine oxidizes to form cystine which has lower solubility and precipitates
Solution Approach 1:
The patent applies parameter changes by adjusting the pH of the cysteine solution to a low range (pH 1.0-2.5), which fundamentally alters the chemical environment to prevent oxidation. This pH modification suppresses the formation of cystine by maintaining cysteine in a reduced state, thereby resolving the contradiction between solution stability and prevention of harmful precipitation.
Solution Approach 2:
The patent employs an inert atmosphere by filling the solution container with nitrogen gas, creating an oxygen-free environment. This prevents oxidative conversion of cysteine to cystine by eliminating the oxidizing agent (oxygen), thus maintaining solution stability without cystine formation.
2Quantity of substance
If conventional cysteine preparations are used, then cysteine is available for parenteral nutrition, but aluminum content reaches up to 5000 μg/L which may exceed the total daily aluminum limit
Solution Approach 1:
The patent applies the extraction principle by removing aluminum from the cysteine solution through careful formulation and manufacturing processes. The solution is prepared to contain less than 400 μg/L aluminum, effectively extracting or eliminating the harmful aluminum contaminant while preserving the therapeutic cysteine component.
Solution Approach 2:
The patent changes the aluminum concentration parameter from conventional levels (up to 5000 μg/L) to a controlled low level (less than 400 μg/L). This parameter modification ensures that cysteine remains available for parenteral nutrition while aluminum toxicity risk is eliminated.
3Duration of action of stationary object
If cysteine is stored in solution for extended periods, then convenience of use is improved, but oxidation to cystine occurs reducing solubility and creating particulate matter
Solution Approach 1:
The patent modifies the pH parameter to a low range (1.0-2.5) and controls dissolved oxygen content, creating a stable chemical environment that prevents oxidation during extended storage. This allows the solution to maintain clarity and stability for long-term storage without forming cystine precipitates.
Solution Approach 2:
The patent uses nitrogen atmosphere to displace oxygen in the storage container, creating an inert environment that prevents oxidative degradation. This enables extended storage duration while maintaining solution reliability and preventing particulate formation.
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 cysteine compositions maintain stability and low aluminum levels over time, preventing cystine formation and reducing the risk of aluminum toxicity, making them suitable for extended storage and safe administration in parenteral nutrition.
Implementation Method 1
the stability of cysteine is low in solution, e.g., it can oxidize to form cystine, a disulfide dimer
Implementation Method 2
prepared using acidified water and nitrogen atmosphere to minimize oxidation
Data Source
AI summary
Cysteine compositions comprising less than about 400 μg/L of aluminum. For example, solutions of cysteine comprising a pharmaceutically acceptable solvent, cysteine, and less than about 145 μg/L of aluminum, wherein the solution is devoid of visible particulate matter. Cysteine compositions described herein may be suitable for injection. For example, disclosed cysteine solutions may be provided intravenously to meet amino acid nutritional requirement in individuals receiving total parenteral nutrition. Also provided are processes for preparing cysteine compositions, and methods for providing cysteine to individuals in need thereof.