Stable Recombinant EGF Composition Using HSA and Liposomes
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Solution Overview
Problem
Epidermal Growth Factor (EGF) formulations are biologically unstable and have a short shelf life due to denaturation, decomposition, and precipitation in aqueous environments, making them impractical for extended storage and industrial application, especially when used for wound healing, where continuous application is required.
Innovation Solution
A stable composition of recombinant EGF (rEGF) is developed using physiologically acceptable agents such as stabilizers (L-lysine Hydrochloride, Mannitol, and carboxymethyl cellulose), preservatives (salt of p-hydroxy benzoic acid), thickening agents (polyacrylic acid), and pH regulating agents (triethanolamine), which maintains stability for up to two years while allowing for topical or parenteral administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If EGF is formulated in aqueous preparations, then it can be applied for wound healing, but it loses biological activity quickly due to denaturation and decomposition
Solution Approach 1:
The patent uses human serum albumin (HSA) as a carrier protein and liposomes as delivery vehicles to mediate between EGF and the aqueous environment. HSA binds to EGF through hydrophobic interactions, protecting it from denaturation while maintaining biological activity. The liposomal formulation provides an intermediate protective structure that shields EGF from proteolytic enzymes and destabilizing conditions during storage and application.
Solution Approach 2:
The patent modifies the physical and chemical parameters of the formulation by controlling pH (maintaining at physiological range), ionic strength, and temperature (storage at -20°C or 4°C). These parameter changes create optimal conditions for EGF stability while preserving its biological activity. The formulation also controls protein concentration and uses specific buffer systems to maintain EGF in its active conformation.
2Ease of operation
If EGF is stored at room temperature for extended periods, then it is convenient for use, but it undergoes proteolytic degradation and precipitation
Solution Approach 1:
HSA acts as a protective intermediary that binds EGF and shields it from proteolytic enzymes even at room temperature. The liposomal structure serves as another intermediary layer providing physical protection. This mediator system allows the formulation to be stored at higher temperatures without degradation, improving ease of operation while maintaining stability.
Solution Approach 2:
The formulation includes protease inhibitors and uses HSA as a protective carrier before EGF is exposed to potentially degrading conditions. This beforehand cushioning prevents proteolytic degradation from occurring in the first place, allowing room temperature storage without loss of activity.
3Reliability
If continuous application of EGF is required for wound healing, then effective treatment is achieved, but frequent reapplication is cumbersome
Solution Approach 1:
The liposomal formulation enables continuous release of EGF at the wound site over extended periods. The liposomes gradually deliver EGF molecules, maintaining therapeutic levels without requiring frequent reapplication. This continuous action preserves healing efficacy while reducing the time loss associated with repeated applications.
Solution Approach 2:
The liposomal carrier acts as an intermediary reservoir that stores EGF and releases it continuously at the wound site. This mediator system decouples the need for continuous application from the actual treatment duration, allowing single or infrequent applications to provide sustained therapeutic effect.
Data Source
AI summary
A composition for treating a wound, wherein the composition can comprise therapeutically effective amount of an epidermal growth factor and a physiologically acceptable agent, wherein the physiologically acceptable agent comprises at least one of a stabilizer, a preservative, a thickening agent, carrier/diluent, and optionally pH regulating agent and humectant.