Stable Insulinotropic Peptide Composition with Preservative
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing insulinotropic peptide multi-dose aqueous parenteral pharmaceutical compositions face challenges in stability due to physical and chemical instability, particularly when preservatives are added, which affects shelf life and market competitiveness.
Innovation Solution
A stable insulinotropic peptide multi-dose injectable aqueous parenteral pharmaceutical composition is developed, comprising GLP-1, mannitol, propylene glycol, phenol, and a pharmaceutically acceptable buffer salt solution of sodium acetate-acetic acid, with a pH value of 3 to 5, allowing for long-term storage and increased stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a preservative is added to ensure antimicrobial effect, then microbial contamination is prevented, but the stability of the insulinotropic peptide deteriorates leading to aggregation and reduced shelf life
Solution Approach 1:
The patent introduces multiple protective agents (excipients) as intermediaries between the preservative and the insulinotropic peptide. These include amino acids (arginine, lysine, histidine), peptides (albumin, casein), and other stabilizing substances that act as mediators to prevent direct harmful interactions between the preservative and the peptide, thereby maintaining both antimicrobial effect and peptide stability
Solution Approach 2:
The patent creates a composite pharmaceutical formulation combining the insulinotropic peptide with multiple protective agents including amino acids, peptides, excipients, and preservatives. This composite system works synergistically where each component contributes to overall stability, allowing the preservative to function without causing peptide aggregation
2Ease of operation
If the pharmaceutical composition is developed as multi-dose aqueous parenteral solution, then patient convenience and production cost are improved, but the physical and chemical stability of the peptide deteriorates
Solution Approach 1:
The patent optimizes multiple formulation parameters including pH (adjusted to 2-3 using hydrochloric acid), concentrations of protective agents (amino acids at 0.1-10%, peptides at 0.1-5%, excipients at 0.1-5%), and preservative levels. These parameter adjustments create an aqueous environment that maintains peptide stability while enabling multi-dose convenience
Solution Approach 2:
Multiple protective agents serve as intermediaries that stabilize the peptide in the aqueous multi-dose formulation, preventing denaturation, aggregation, and degradation that would otherwise occur in water-based solutions over extended storage periods
3Duration of action of stationary object
If the peptide is formulated as lyophilized injection powder, then shelf life is extended, but patient convenience and production cost deteriorate
Solution Approach 1:
The patent inverts the conventional approach by formulating a stable aqueous solution instead of requiring lyophilization. Through careful selection and optimization of protective agents and formulation parameters, the patent achieves long-term stability (2 years at 4°C) in the aqueous state, eliminating the need for freezing-drying while maintaining shelf life
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 composition achieves greater stability for GLP-1, enabling storage for 2 years at 4°C even after the addition of a preservative, thereby improving shelf life and market competitiveness while maintaining effective antimicrobial properties.
Implementation Method 1
Dissolution enhancers selected for most proteins or polypeptides are surfactants and PEG. Surfactants are mostly Tween, Span, Poloxamer, Pluronic, Brij and the like. In addition to these substances, surfactants selected in the present invention further include propylene glycol and dextran. Propylene glycol and dextran have very good effects when used as GLP-1 dissolution enhancers.
Implementation Method 2
In the development of multi-dose aqueous parenteral pharmaceutical compositions, adding a preservative into the pharmaceutical composition must be taken into consideration, so as to ensure that there is no microbial contamination during the storage duration and the usage period.
Implementation Method 3
a pharmaceutically acceptable buffer salt solution of sodium acetate-acetic acid (NaAc-HAc); wherein, the aqueous parenteral pharmaceutical composition has a pH value of 3 to 5
Implementation Method 4
Physical instability includes, for example, denaturation, surface adsorption, aggregation, precipitation, gelatination, and the like
Implementation Method 5
chemical instability includes, for example, hydrolysis, deamination, oxidization, racemization, isomerization, β-elimination, disulfide bond exchange, and the like
Data Source
AI summary
This invention is an insulinotropic peptide multi-dose aqueous parenteral pharmaceutical composition and use thereof. A long-term storage formulation of the insulinotropic peptide can be obtained via the method of the present invention. The pharmaceutical composition of the present invention comprises: insulinotropic peptide, insulinotropic peptide analogue and derivative; pharmaceutically acceptable tonicity modifier (stabilizer); pharmaceutically acceptable preservative; and pharmaceutically acceptable dissolution enhancer and pharmaceutically acceptable buffer solution. The pharmaceutical composition of the insulinotropic peptide is used in the preparation of drugs for treating diabetes and adiposis.