Ophthalmic Emulsion Stability via C16-Quaternary Ammonium Segmentation

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Solution Overview

Problem

Existing ophthalmic emulsions containing quaternary ammonium compounds face challenges in achieving stability and reducing toxicity, particularly when using long chain alkyl groups which can result in poor bactericidal activity and undesirable preservative effects.

Innovation Solution

A cationic oil-in-water emulsion comprising a reduced amount of C16-alkyl quaternary ammonium halides, such as C16-alkylbenzyl ammonium halides, which provides enhanced stability and reduced toxicity by preferentially localizing at the oil/water interface, maintaining a positive zeta potential and minimizing presence in the aqueous phase.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If long chain quaternary ammonium compounds (C14-C18) are used as cationic agents in emulsions, then the cationic power and emulsion stability are enhanced, but the bactericidal activity is reduced

Engineering Contradiction:

Improveemulsion stabilityVSAvoidpoor bactericidal activity

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent segments the quaternary ammonium compound population by using a mixture of different alkyl chain lengths (C12, C14, C16, C18) rather than a single long chain compound. This segmentation allows different components to perform different functions: shorter chains (C12-C14) provide bactericidal activity while longer chains (C16-C18) provide cationic power and stability, thus resolving the contradiction between stability and bactericidal activity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent changes the parameter of alkyl chain length distribution by specifying a particular mixture composition (60-70% C12, 30-40% C14, <5% C16, <5% C18). This parameter change optimizes the balance between cationic power and bactericidal activity, achieving both emulsion stability and adequate preservative effect simultaneously

Inventive Principle:

Principle #35Parameter changes

2Reliability

If quaternary ammonium compounds are used as preservative agents in emulsions, then preservative efficacy is achieved, but toxicity to ocular tissues increases

Engineering Contradiction:

Improvepreservative efficacyVSAvoidocular toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the concentration parameter of quaternary ammonium compounds by specifying a reduced content range (0.001% to 0.1% w/w, preferably 0.005% to 0.05%). This parameter reduction maintains adequate preservative efficacy while significantly reducing ocular toxicity compared to conventional higher concentrations

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses a composite mixture of quaternary ammonium compounds with different alkyl chain lengths rather than a single compound. This composite approach provides synergistic effects where the mixture achieves better preservative efficacy at lower total concentrations, thereby reducing toxicity while maintaining protection

Inventive Principle:

Principle #40Composite materials

3Adaptability or versatility

If mixtures of benzalkonium chlorides with various alkyl chain lengths are used, then both preservative and cationic agent functions are achieved, but emulsion stability is reduced

Engineering Contradiction:

Improvedual function (preservative and cationic agent)VSAvoidemulsion stability

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent optimizes the parameter of alkyl chain length distribution by specifying precise ranges (60-70% C12, 30-40% C14, <5% C16, <5% C18). This optimized distribution ensures adequate cationic power for stability while maintaining preservative efficacy, resolving the stability issue that plagues conventional mixtures

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20230181738A1Oil-in-water emulsions comprising cetalkonium chloride and methods of making and using the same

Publication Date: 2023.06.15 SANTEN SAS

AI summary

Compositions containing quaternary compounds in which the nitrogen atom is substituted by at least one alkyl group having at least 12 carbon atoms, and the composition includes at least 20% in weight by weight of the total composition, of ammonium halides in which the nitrogen atom is substituted by at least one alkyl group having at least 14 carbon atoms and more than 5%, preferably more than 7% in weight by weight of the total composition, of ammonium halides in which the nitrogen atom is substituted by at least one alkyl group having at least 16 carbon atoms. Also, ophthalmic oil-in-water emulsions containing such compositions, the ophthalmic emulsions being useful for eye care or for the treatment of eye conditions.