Buffer-Free Liquid Gonadotropin Formulation for Oxidation Stability
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Solution Overview
Problem
Existing gonadotropin formulations, particularly liquid formulations, are unstable and prone to degradation, especially when containing preservatives, leading to issues such as oxidation and instability over time, which affects their efficacy in treating infertility.
Innovation Solution
A stable liquid gonadotropin formulation comprising arginine and methionine without the addition of a buffer, with specific pH levels between 6.0 and 7.5, which stabilizes gonadotropins like hCG and FSH, ensuring stability for up to 24 months at room temperature.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If liquid gonadotropin formulations contain preservatives to maintain sterility, then microbial stability is improved, but chemical stability deteriorates due to oxidation and degradation
Solution Approach 1:
The patent introduces arginine and methionine as intermediary substances that mediate between the preservative requirements and chemical stability needs. These amino acids act as stabilizing agents that protect gonadotropins from oxidation and degradation while allowing the formulation to maintain preservatives for microbial stability, thus resolving the contradiction between microbial and chemical stability
Solution Approach 2:
The patent changes the chemical parameters of the formulation by adjusting pH to a neutral range (7.0-7.5) and incorporating specific amino acid concentrations (arginine 50-160 mM, methionine 0.05-1.5 mg/ml). These parameter changes create a formulation environment that simultaneously supports both microbial stability through preservative compatibility and chemical stability through oxidation protection
2Stability of the object's composition
If buffers are added to maintain pH stability in gonadotropin formulations, then pH control is improved, but formulation complexity and potential oxidation catalysis increase
Solution Approach 1:
The patent extracts and removes the buffer component from traditional gonadotropin formulations. Instead of adding buffers to control pH, the invention achieves pH stability through a different approach: using arginine and methionine as stabilizing agents that maintain pH within 7.0-7.5 without requiring additional buffer substances, thus reducing formulation complexity while maintaining pH control
Solution Approach 2:
The formulation system becomes self-regulating through the inherent buffer capacity of arginine and methionine themselves, which can accept or donate protons as needed. This self-service mechanism eliminates the need for separate buffer additives, reducing complexity while maintaining pH stability through the amino acids' own chemical properties
3Ease of operation
If gonadotropin formulations are stored at room temperature for extended periods, then ease of storage is improved, but stability deteriorates due to oxidation and degradation
Solution Approach 1:
The patent applies preliminary protective action by incorporating arginine and methionine into the formulation before storage. These amino acids pre-establish oxidation protection and stability mechanisms that remain active throughout storage at room temperature, preventing degradation before it occurs rather than addressing it after stabilization is compromised
Solution Approach 2:
The invention uses inexpensive, simple amino acid compounds (arginine and methionine) as stable, long-lasting protective agents. These small molecules provide sustained oxidation protection throughout the entire storage period without requiring complex systems or expensive additives, making the stability protection both economical and durable
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 formulation maintains high stability and minimizes oxidation, allowing for effective use in treating infertility through methods like ovulation induction and assisted reproductive technologies, with reduced injection-related side effects.
Implementation Method 1
The formulation maintains high stability and minimizes oxidation
Data Source
AI summary
The present invention pertains in general to the field of the stabilization of gonadotropin formulations, in particular liquid formulations of gonadotropins. The stabilization is achieved by a particular combination of excipients, preferably arginine and methionine. In a preferred embodiment, the formulation does not comprise a buffer.