Cyclosporin A Ophthalmic Solution Using Ternary Polymers

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Solution Overview

Problem

Current ophthalmic formulations of cyclosporin A for treating dry eye and loss of corneal sensitivity face challenges due to its low solubility in aqueous media, leading to instability and poor tolerance upon instillation, with existing solutions often relying on oily emulsions or hydro-alcoholic compositions that cause irritation.

Innovation Solution

A stable aqueous ophthalmic solution is developed using a ternary polymeric system comprising cyclosporin A, a cellulose derivative, and a polyvinyl derivative, along with macrogolglycerol hydroxystearate, which solubilizes the immunosuppressive agent effectively without preservatives, ensuring good tolerance and penetration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If cyclosporin A is formulated in aqueous solution, then tolerability and penetration are improved, but solubility becomes insufficient

Engineering Contradiction:
ImprovetolerabilityVSAvoidsolubility
Core Design Contradiction:
Ease of operationVSQuantity of substance

Solution Approach 1:

The patent introduces a ternary polymeric system (comprising a cellulosic derivative, a polyvinyl derivative, and macrogolglycerol hydroxystearate) as intermediary substances that mediate between cyclosporin A and aqueous media. These polymers form a complex structure that solubilizes the hydrophobic cyclosporin A in water, enabling both high solubility and good tolerability simultaneously.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite formulation by combining three different polymers in a specific ratio within an aqueous solution. This composite polymeric system leverages the complementary properties of each polymer to achieve both high solubility of cyclosporin A and excellent tolerability, resolving the contradiction between these two properties.

Inventive Principle:
Principle #40Composite materials

2Quantity of substance

If cyclosporin A is formulated in oily emulsion, then solubility is improved, but tolerability and penetration deteriorate

Engineering Contradiction:
ImprovesolubilityVSAvoidtolerability
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The patent fundamentally changes the formulation parameter from oily emulsion to aqueous solution by incorporating a ternary polymeric system. This parameter change allows cyclosporin A to maintain high solubility while achieving superior tolerability and penetration, as the aqueous formulation with polymers provides better ocular compatibility than traditional oily emulsions.

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If preservatives are added to the formulation, then stability is improved, but tolerability deteriorates

Engineering Contradiction:
ImprovestabilityVSAvoidirritation
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent employs a preservative-free formulation strategy, utilizing the ternary polymeric system to provide sufficient stability without requiring traditional preservatives. This approach eliminates the harmful effects of preservative-induced irritation while maintaining formulation stability through the inherent properties of the polymer complex.

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

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 solution provides a therapeutically effective concentration of cyclosporin A with improved stability and tolerance, allowing for better penetration into the cornea without irritation, addressing the limitations of existing formulations.

Implementation Method 1

a ternary polymeric system allowing its solubilization in a therapeutically effective quantity and with high stability

Methodology Applied
Scientific EffectSolubilization: Solvation

Implementation Method 2

macrogolglycerol hydroxystearate, which solubilizes the immunosuppressive agent effectively

Methodology Applied
Scientific EffectSurfactant action: Surfactant

Data Source

PatentEP2827840B1Cyclosporin a-based aqueous ophthalmic solution
Publication Date: 2019.08.28 LABORATOIRES THEA SAS
  • EP2827840B1 patent drawingFigure 1A~1B
  • EP2827840B1 patent drawingFigure 2
  • EP2827840B1 patent drawing

AI summary

The present invention relates to an aqueous ophthalmic solution comprising an immunosuppressive agent such as cyclosporin A and at least three polymers. The invention advantageously relates to the combination of a cellulose derivative, a polyvinyl derivative and a macrogolglyercol hydroxystearate.