Polysaccharide Ether Micelles for Thermal Stable Ophthalmic Viscosupplementation

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Solution Overview

Problem

Current ophthalmological viscoelastic devices, particularly those based on hyaluronic acid and hydroxypropyl methylcellulose, face challenges such as high production costs, thermal sensitivity, and viscosity loss during steam sterilization, limiting their accessibility and effectiveness in medical applications.

Innovation Solution

Development of water-soluble polysaccharide ethers with mesogenic side groups, such as cholesteryl derivatives, which form star-shaped fringe micelles in aqueous solutions, achieving high zero-shear viscosities and pseudo-plasticity similar to hyaluronic acid without temperature sensitivity, allowing for stable and injectable viscoelastic preparations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If hyaluronic acid is used as base polymer for ophthalmological viscoelastic devices, then good flow properties and tissue protection are achieved, but production costs are high and there is risk of BSE/TSE transmission

Engineering Contradiction:
Improveflow propertiesVSAvoidproduction cost and transmission risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces expensive animal-derived hyaluronic acid with synthetic polysaccharide ethers that can be produced more economically from plant-based cellulose sources, eliminating the need for costly animal tissue extraction while maintaining the required viscoelastic properties for ophthalmological applications

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention creates composite structures by combining polysaccharide ether backbones with mesogenic side groups to form hybrid molecules that exhibit both the desired rheological properties of hyaluronic acid and the thermal stability of synthetic polymers, achieving a material that combines benefits of natural and synthetic systems

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If fermentation-produced hyaluronic acid is used, then BSE/TSE risk is reduced, but molecular weight and zero-shear viscosity are lower

Engineering Contradiction:
ImproveBSE/TSE riskVSAvoidmolecular weight
Core Design Contradiction:
Object-affected harmful factorsVSQuantity of substance

Solution Approach 1:

The patent systematically varies parameters including degree of substitution, molecular weight of base polysaccharide, and mesogenic group composition to optimize the balance between safety (eliminating animal sources) and performance (achieving high molecular weight and viscosity), producing a range of tailored viscoelastic materials

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If bacterial hyaluronic acid is used, then production is more accessible, but aqueous solutions are thermally sensitive and viscosity is lost during steam sterilization

Engineering Contradiction:
Improveproduction accessibilityVSAvoidthermal stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent substitutes the thermally sensitive natural hyaluronic acid polymer structure with a synthetic polysaccharide ether framework that possesses inherent thermal stability, allowing the material to withstand autoclaving and other sterilization processes without degradation, while maintaining the desired viscoelastic flow properties

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention introduces mesogenic side groups at specific positions on the polysaccharide ether backbone to create localized regions of enhanced thermal stability and structured aggregation, while the bulk polymer structure maintains the flexible, shear-thinning characteristics necessary for ophthalmological application

Inventive Principle:
Principle #3Local quality

4Quantity of substance

If high concentrations of HPMC are used to attain high zero-shear viscosities, then viscosity is improved, but compatible osmolalities cannot be maintained

Engineering Contradiction:
Improvezero-shear viscosityVSAvoidosmolality
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent designs composite polysaccharide ether molecules with mesogenic side groups that self-assemble into structured aggregates in aqueous solution, creating high viscosity through supramolecular organization rather than relying on high polymer concentration, thereby maintaining physiological osmolality and biocompatibility

Inventive Principle:
Principle #40Composite materials

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 modified polysaccharide ethers provide stable, injectable viscoelastic solutions with enhanced rheological properties, maintaining viscosity under shear forces and during steam sterilization, addressing the limitations of existing products and enabling cost-effective, thermally stable viscoelastic preparations for medical use.

Implementation Method 1

which form star-shaped fringe micelles in aqueous solutions

Methodology Applied
Scientific EffectMicelle formation: Microemulsion

Implementation Method 2

achieving high zero-shear viscosities and pseudo-plasticity similar to hyaluronic acid

Methodology Applied
Scientific EffectPseudo-plasticity: Non-Newtonian Fluids

Implementation Method 3

maintaining viscosity under shear forces and during steam sterilization

Methodology Applied
Scientific EffectViscoelasticity: Viscoelasticity

Implementation Method 4

allowing for stable and injectable viscoelastic preparations

Methodology Applied
Scientific EffectThermal stability: Thermal Insulation

Data Source

PatentUS9045565B2Water-soluble polysaccharide ethers and their use
Publication Date: 2015.06.02 PHARMPUR

AI summary

The invention relates to modified polysaccharide ethers having a weight-averaged molecular weight of 40,000 to 500,000 g/mole, zero shear viscosity of more than 10 Pa·s, and pseudo-plasticity of more than 20. These modified polysaccharide ethers are obtainable by reacting cellulose-based polysaccharide ether(s) with at least one mesogenic modification agent or modified polysaccharide ethers, obtainable by reacting polysaccharide ether(s) selected from hydroxypropylmethyl cellulose (HPMC), hydroxyethylmethyl cellulose (HEMC), methyl cellulose, and cellulose ethers with methyl and/or ethyl and/or propyl groups and mixtures thereof, with at least one mesogenic modification agent. These substances can be used to produce gel-like to stable aqueous preparations having viscoelastic flow properties, which are suited for use in the human body, particularly within the scope of ophthalmologic procedures.