Hyaluronic Acid Composition Viscosity Control During Sterilization

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Solution Overview

Problem

Hyaluronic acid compositions for injection become more rigid or viscous after sterilization due to heat treatment, which can be counterproductive in applications requiring shallow injections or fine needles, and the addition of common anaesthetics like lidocaine exacerbates this issue.

Innovation Solution

Incorporating a small amount of an ascorbic acid derivative, such as ascorbyl phosphates, ascorbyl sulfates, or ascorbyl glycosides, into the hyaluronic acid composition with a local anesthetic to reduce the viscosity and elastic modulus caused by sterilization, allowing for finer needle use without increasing expulsion force and maintaining the composition's properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If heat treatment sterilization is applied to hyaluronic acid composition, then sterilization is achieved, but the composition becomes more rigid or viscous

Engineering Contradiction:
ImprovesterilizationVSAvoidinjectability
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

An ascorbic acid derivative is added to the hyaluronic acid composition before sterilization to preemptively counteract the viscosity-increasing effect of heat treatment. This preliminary addition ensures that when autoclaving occurs, the derivative is already present to mitigate rigidity changes, maintaining optimal injectability throughout the sterilization process and beyond.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The ascorbic acid derivative acts as an intermediary substance between the heat treatment process and the hyaluronic acid composition. It mediates the interaction by absorbing or neutralizing the harmful thermal effects that would otherwise increase viscosity and rigidity, thereby protecting the composition's injectability while still allowing sterilization to occur.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If local anesthetic is added to hyaluronic acid composition, then pain reduction is achieved, but the composition becomes more viscous after sterilization

Engineering Contradiction:
Improvepain reductionVSAvoidinjectability
Core Design Contradiction:
Object-affected harmful factorsVSEase of operation

Solution Approach 1:

The ascorbic acid derivative serves as an intermediary that counteracts the interaction between the local anesthetic and the heat sterilization process. It mitigates the synergistic effect that would otherwise cause excessive viscosity increase, allowing both the anesthetic's pain-relieving properties and the composition's injectability to coexist.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The ascorbic acid derivative modifies the rheological parameters of the composition, specifically counteracting changes in viscosity and elastic modulus that would result from the combination of local anesthetic and heat sterilization. This parameter adjustment maintains optimal flow characteristics for injection while preserving the anesthetic's functionality.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If ascorbic acid derivative is added to reduce viscosity, then injectability is improved, but the composition stability may be affected

Engineering Contradiction:
ImproveinjectabilityVSAvoidcomposition stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The ascorbic acid derivative is selected and dosed to achieve specific rheological parameter changes that improve injectability while staying within stability-preserving thresholds. By carefully controlling the derivative's concentration and molecular properties, the composition's flow characteristics are optimized without compromising its structural integrity or long-term stability.

Inventive Principle:
Principle #35Parameter changes

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 addition of ascorbic acid derivatives effectively counteracts the viscosity increase caused by sterilization, facilitating the use of finer needles and improving skin morphology, collagen formation, and providing anti-inflammatory and photoprotective benefits without significantly affecting the stability of the hyaluronic acid composition.

Implementation Method 1

addition of a relatively small amount of an ascorbic acid derivative selected from the group consisting of ascorbyl phosphates, ascorbyl sulfates and ascorbyl glycosides to a hyaluronic acid composition comprising a local anesthetic selected from the group consisting of amide and ester type local anesthetics may effectively reduce the 'viscosity increase' of the hyaluronic acid composition caused by the local anesthetic upon sterilization of the composition by autoclave

Methodology Applied
Scientific EffectViscosity reduction effect:

Implementation Method 2

Sterilization is generally performed by heat treatment, such as autoclaving. The heat treatment generally leads to a reduction of the rigidity or viscosity of the hyaluronic acid composition.

Methodology Applied
Scientific EffectHeat treatment sterilization: Heat Treatment

Implementation Method 3

As ascorbic acid and its derivatives can improve the collagen formation, they may enhance skin morphology.

Methodology Applied
Scientific EffectCollagen formation enhancement:

Implementation Method 4

They may also improve epidermal barrier formation, reduce transepidermal water loss, improve wound healing, and thus play an important role in prevention of skin aging and associated dry skin conditions. Ascorbic acid and its derivatives are known for their anti-inflammatory and photoprotective properties

Methodology Applied
Scientific EffectAnti-inflammatory effect:

Data Source

PatentEP2670447B2Hyaluronic acid composition comprising an ascorbic acid derivative
Publication Date: 2024.04.24 Q MED AB
  • EP2670447B2 patent drawingFigure 1~2
  • EP2670447B2 patent drawingFigure 3~4
  • EP2670447B2 patent drawingFigure 5~6

AI summary

The present invention relates toan injectable hyaluronic acid composition comprising a hyaluronic acid; a local anesthetic selected from the group consisting of amide and ester type local anesthetics or a combination thereof; and an ascorbic acid derivativein an amount which prevents or reduces the effect on the viscosity and/or elastic modulus G' of the composition caused by the local anesthetic upon sterilization by heat. The present invention further relates to the medical and non-medical, such as cosmetic, use of such a composition, and to a method of manufacturing such a composition. Figure