Liquid Gonadotropin Formulation Without Buffer 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, effectively stabilizing 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 specific range (6.0-7.5) 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 and chemical stability, eliminating the need to choose one over the other
2Stability of the object's composition
If buffer solutions are added to maintain pH stability, then pH control is improved, but formulation complexity and potential side effects increase
Solution Approach 1:
The patent extracts and eliminates 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 in specific concentrations combined with controlled pH adjustment during formulation, thereby reducing formulation complexity while maintaining pH stability
Solution Approach 2:
The patent replaces complex buffer systems with simpler, more economical stabilizing agents. Arginine and methionine serve as cost-effective alternatives to traditional buffers, providing sufficient stabilization without the complexity of multiple buffer components, making the formulation more simple and potentially reducing injection-related side effects
3Duration of action of stationary object
If formulation is designed for long-term storage stability, then shelf life is improved, but activity and efficacy may be compromised due to degradation
Solution Approach 1:
The patent applies preliminary protective actions by incorporating arginine and methionine into the formulation at the time of manufacture. These stabilizing amino acids are pre-positioned to prevent oxidation and degradation pathways from occurring during storage, thereby preserving biological activity throughout the extended shelf life period without requiring additional interventions
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 the stability and activity of gonadotropins, reducing oxidation and ensuring effective treatment of infertility through improved shelf life and reduced injection-related side effects.
Implementation Method 1
The formulation maintains the stability and activity of gonadotropins, reducing 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.