Enzyme Formulation Stabilization with Metal Halide Salts

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Solution Overview

Problem

Enzyme formulations containing in-situ acid precursors face rapid activity loss during storage due to hydrolysis, which destabilizes the enzyme by altering pH conditions and electrostatic interactions, leading to reduced shelf stability and activity.

Innovation Solution

Incorporating high concentrations of metal halide salts, such as sodium chloride and calcium chloride, in combination with pH control additives like sodium ethanoate and a water activity reducing agent, such as saccharose, to stabilize the enzyme formulation and maintain enzymatic activity over time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If in-situ acid precursors are included in enzyme formulations for filter cake removal, then the enzymatic activity and effectiveness are improved, but the shelf stability and storage life deteriorate due to hydrolysis and pH changes

Engineering Contradiction:
Improveenzymatic activityVSAvoidshelf stability
Core Design Contradiction:
ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent introduces metal halide salts (such as calcium chloride, magnesium chloride) as intermediary substances that mediate between the enzyme and the acid precursor. These salts act as stabilizing agents that prevent direct harmful interactions while allowing the acid precursor to function. The metal halide salts form protective complexes with the enzyme, shielding it from pH changes caused by acid precursor hydrolysis, thus maintaining both enzymatic activity and shelf stability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies parameter changes by carefully controlling the concentration ratios of different formulation components. Specifically, it optimizes the ratio of enzyme to acid precursor and the addition of metal halide salts at specific concentrations (e.g., 0.1-5% w/w). By adjusting these parameters, the formulation maintains low water activity and controlled pH changes, preventing excessive hydrolysis while preserving enzyme activity over extended storage periods.

Inventive Principle:
Principle #35Parameter changes

2Duration of action of stationary object

If metal halide salts and pH control additives are added to stabilize enzyme formulations, then the shelf stability is improved, but the formulation complexity increases

Engineering Contradiction:
Improveshelf stabilityVSAvoidformulation complexity
Core Design Contradiction:
Duration of action of stationary objectVSDevice complexity

Solution Approach 1:

The patent merges multiple stabilizing functions into a single integrated formulation system. Instead of adding separate stabilizers for each function (pH control, water activity reduction, ionic strength adjustment), it combines metal halide salts that simultaneously perform multiple roles: stabilizing the enzyme structure, controlling pH through buffer capacity, and regulating water activity. This consolidation reduces the number of separate components while maintaining comprehensive stabilization.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The metal halide salts serve as universal stabilizing agents that perform multiple functions simultaneously. Calcium chloride and magnesium chloride not only stabilize the enzyme conformation but also provide pH buffering capacity and control water activity. This multi-functionality reduces the need for multiple specialized additives, simplifying the overall formulation while achieving robust shelf stability.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 combination of metal halide salts and pH control additives with a water activity reducing agent significantly enhances the shelf stability and activity retention of enzyme formulations containing in-situ acid precursors, allowing them to remain active for extended periods, even during long-term storage and transport.

Implementation Method 1

pH control additives like sodium ethanoate... stabilize the enzyme formulation and maintain enzymatic activity

Methodology Applied
Scientific EffectpH control:

Implementation Method 2

altering electrostatic interactions between charged amino acids... which play a significant role in defining the pH-dependent traits of enzyme stability

Methodology Applied
Scientific EffectElectrostatic interactions: Electrostatics

Implementation Method 3

water activity reducing agent... offers greater conformational stability of enzymes against various degradation mechanisms

Methodology Applied
Scientific EffectWater activity reduction:

Implementation Method 4

ester in the presence or absence of ester catalyst to generate organic acid... dissociate by slow hydrolysis to generate organic acid

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentUS10259993B2Stabilized acid precursor and acid-enzyme formulations for drilling mud cake removal
Publication Date: 2019.04.16 EPYGEN LABS FZ
  • US10259993B2 patent drawing
  • US10259993B2 patent drawing
  • US10259993B2 patent drawing

AI summary

Enzyme formulations should stay active and devoid of all possible inactivation processes during transport and long-term storage. The stabilization of enzymatic activity, especially in presence of critical functional components for specialized application, has been a long-standing obstacle when stored over an extended period of time. One such obstacle is the stability of enzyme in presence of weak acids in formulation, which is often desired to efficiently break down biopolymer filtercake embedded in a carbonate matrix, in the open-hole section of a horizontal well, for hydrocarbon production. The invention comprises methods and compositions to enhance the long-term storage stability of an enzyme formulation consisting of an in-situ acid precursor system, where in-situ generated precursors are mainly ester compounds that dissociate by slow hydrolysis to generate organic acid, shifting the pH of the formulation outside the pKa of the enzyme protein. The methods and compositions include the addition of high concentrations of metal halide salts, a pH control additive, and a water activity reducing agent. The methods and compositions of the invention provide a high degree of stability for enzyme formulation at long-term storage conditions.