Self-Preserved Ophthalmic Compositions via Zinc Borate Synergy

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Solution Overview

Problem

Multi-dose pharmaceutical compositions, particularly ophthalmic solutions, face challenges in maintaining sterility without conventional antimicrobial preservatives, as lower concentrations may not ensure sufficient antimicrobial efficacy while higher concentrations can be toxic to the cornea, risking microbial contamination and infections.

Innovation Solution

Incorporating a combination of borate/polyol complexes and zinc ions in specific concentrations to enhance antimicrobial activity, eliminating the need for conventional preservatives and ensuring compliance with USP preservative efficacy requirements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antimicrobial preservatives are used at higher concentrations to ensure sufficient antimicrobial efficacy, then microbial contamination is prevented, but toxicological effects on the cornea increase

Engineering Contradiction:
Improveantimicrobial efficacyVSAvoidtoxicological effects on cornea
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical parameters of the preservative system by using zinc ions in combination with borate/polyol complexes, allowing effective antimicrobial activity at much lower concentrations than conventional preservatives, thus avoiding corneal toxicity while maintaining reliability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite preservative system combining zinc ions with borate/polyol complexes, where the synergistic interaction between components enhances antimicrobial efficacy at low concentrations, resolving the contradiction between effectiveness and safety

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If conventional antimicrobial preservatives are used at lower concentrations to reduce toxicological effects, then corneal safety is improved, but antimicrobial efficacy becomes insufficient

Engineering Contradiction:
Improvetoxicological effects on corneaVSAvoidantimicrobial efficacy
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent changes the chemical parameters by introducing zinc ions that enhance the antimicrobial activity of borate/polyol complexes, enabling sufficient efficacy at low concentrations without compromising safety

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Zinc ions act as an intermediary that amplifies the antimicrobial activity of the borate/polyol complex system, allowing low concentrations to achieve high efficacy through synergistic interaction

Inventive Principle:
Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If multi-dose pharmaceutical compositions are formulated without conventional antimicrobial preservatives to eliminate toxicological risks, then corneal safety is improved, but risk of microbial contamination increases

Engineering Contradiction:
Improvetoxicological effectsVSAvoidprotection against microbial contamination
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent extracts and eliminates conventional antimicrobial preservatives (such as benzalkonium chloride or polyquaternium-1) from the formulation, replacing them with a naturally derived zinc ion and borate/polyol complex system that provides preservation without toxicity

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The composition achieves self-preservation through the inherent antimicrobial activity of zinc ions and borate/polyol complexes, eliminating the need for external conventional preservatives while maintaining protection against microbial contamination

Inventive Principle:
Principle #25Self-service

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 compositions effectively reduce microbial populations by 90% within seven days and 99.9% within fourteen days, maintaining sterility without the use of conventional antimicrobial agents, thus minimizing toxicological risks and preventing ophthalmic infections.

Implementation Method 1

The ability to achieve self-preservation is based on a unique combination of formulation components and criteria... Incorporating a combination of borate/polyol complexes and zinc ions in specific concentrations to enhance antimicrobial activity

Methodology Applied
Scientific EffectSynergistic interaction:

Data Source

PatentEP2066300B2Self-preserved aqueous pharmaceutical compositions
Publication Date: 2019.01.23 NOVARTIS AG

AI summary

The use of a borate/polyol and zinc system to enhance the antimicrobial activity of multi-dose pharmaceutical compositions is described. The compositions do not require a conventional anti-microbial preservative and therefore are referred to as being 'self-preserved'. The compositions possess sufficient antimicrobial activity to satisfy the preservative efficacy requirements of the USP for aqueous ophthalmic compositions.