Injectable L-Cysteine Composition With Oxygen-Controlled Purity
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Solution Overview
Problem
Existing L-cysteine compositions for parenteral administration suffer from instability and unsafe levels of impurities such as Aluminum, cystine, pyruvic acid, and heavy metals, posing risks to vulnerable patient populations like preterm infants and critically ill adults.
Innovation Solution
Formulations with controlled levels of Aluminum (1.0-250 ppb), cystine (0.001-2.0 wt%), pyruvic acid (0.001-2.0 wt%), and dissolved oxygen (0.1-5 ppm) in a pharmaceutically acceptable carrier, enclosed in a single-use container, to ensure stability and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If L-cysteine compositions are prepared for parenteral administration, then the therapeutic benefit is achieved, but the compositions suffer from instability and unsafe levels of impurities such as Aluminum, cystine, pyruvic acid, and heavy metals
Solution Approach 1:
The patent applies parameter changes by establishing specific concentration ranges for L-cysteine (10-100 mg/mL) and controlling impurity levels (Aluminum: 1.0-250 ppb, cystine: 0.001-2.0 wt%, pyruvic acid: 0.001-2.0 wt%). These parameter specifications transform the unstable, impurity-laden composition into a stable, safe product suitable for prolonged parenteral administration
Solution Approach 2:
The patent utilizes an inert environment by enclosing the composition in a single-use container with controlled headspace oxygen levels (0.5-4.0%) and dissolved oxygen (0.1-5 ppm). This oxygen-controlled inert atmosphere prevents oxidation of L-cysteine to cystine and degradation to pyruvic acid, thereby maintaining stability and minimizing harmful impurities over extended storage periods
2Adaptability or versatility
If L-cysteine is administered to vulnerable patient populations such as preterm infants and critically ill adults, then the nutritional benefit is achieved, but the risk of Aluminum toxicity and other impurity-related adverse effects increases
Solution Approach 1:
The patent applies parameter changes by establishing strict impurity thresholds (Aluminum: 1.0-250 ppb, cystine: 0.001-2.0 wt%, pyruvic acid: 0.001-2.0 wt%) that are specifically designed to be safe for vulnerable populations including preterm infants and critically ill adults. These parameter specifications ensure the composition can be administered for prolonged periods without accumulating toxic levels of impurities
Solution Approach 2:
The patent employs a single-use container system that is discarded after one use. This disposable approach prevents contamination from repeated access, eliminates the risk of post-preparation contamination, and ensures that each administration uses a fresh, sterile composition with guaranteed impurity levels, thereby protecting vulnerable patients from Aluminum toxicity and other adverse effects
3Duration of action of stationary object
If the composition is stored for extended periods, then the availability for prolonged administration is improved, but the stability and purity of the composition deteriorates
Solution Approach 1:
The patent utilizes an inert environment by controlling oxygen levels in the headspace (0.5-4.0%) and dissolved phase (0.1-5 ppm) of the container. This oxygen-controlled atmosphere prevents oxidative degradation of L-cysteine during extended storage, maintaining purity and stability for prolonged periods and enabling availability for prolonged administration
Solution Approach 2:
The patent applies parameter changes by specifying L-cysteine concentration (10-100 mg/mL) and establishing acceptable ranges for impurities (Aluminum: 1.0-250 ppb, cystine: 0.001-2.0 wt%, pyruvic acid: 0.001-2.0 wt%) that remain stable over extended storage. These parameter specifications ensure the composition maintains its therapeutic efficacy and safety profile throughout the intended storage period
Data Source
AI summary
The subject matter described herein is directed to stable L-cysteine compositions for injection, comprising: L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof in an amount from about 10 mg/mL to about 100 mg/mL; Aluminum in an amount from about 1.0 parts per billion (ppb) to about 250 ppb; cystine in an amount from about 0.01 wt % to about 2 wt % relative to L-cysteine; pyruvic acid in an amount from about 0.01 wt % to about 2 wt % relative to L-cysteine; a pharmaceutically acceptable carrier, comprising water; headspace O2 that is less than 1.0%; dissolved oxygen present in the carrier in an amount from about 0.01 parts per million (ppm) to about 1 ppm, wherein the composition is enclosed in a single-use container having a volume of from 10 mL to 100 mL. Also described are compositions for a total parenteral nutrition regimen and methods for their use.