Propofol Emulsion Preservative System for Microbial Control

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Solution Overview

Problem

Current Propofol emulsion compositions for intravenous administration face challenges with microbial growth due to the presence of vegetable oils and phospholipids, leading to potential nosocomial infections, and existing preservatives either cause instability or toxicity at higher concentrations.

Innovation Solution

A stable Propofol oil-in-water emulsion composition incorporating triglyceride oils, purified and/or modified natural phosphatides, tonicity modifying agents, and a preservative system comprising monoglyceryl ester of lauric acid (Monolaurin) along with capric acid and/or its salts or edetate, which effectively prevents microbial growth without causing instability or toxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If vegetable oils and phospholipids are used to formulate Propofol emulsion, then the emulsion achieves rapid onset anesthesia and short recovery time, but the emulsion becomes highly prone to microbial growth

Engineering Contradiction:
Improveonset speedVSAvoidmicrobial growth
Core Design Contradiction:
SpeedVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a preservative system comprising monoglyceryl ester of lauric acid (Monolaurin) combined with capric acid and/or its salts or edetate as an intermediary substance that mediates between the Propofol emulsion formulation and microbial contamination. This preservative system effectively inhibits microbial growth while maintaining the emulsion's stability and pharmacological properties, resolving the contradiction between rapid onset anesthesia and susceptibility to microbial growth.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If preservatives are added to prevent microbial growth, then antimicrobial activity is improved, but emulsion stability deteriorates

Engineering Contradiction:
Improvemicrobial growthVSAvoidemulsion stability
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent optimizes the concentration parameters of the preservative system, using monoglyceryl ester of lauric acid at specific concentrations combined with capric acid and/or its salts or edetate. By carefully controlling the parameter ranges of these preservatives, the formulation achieves sufficient antimicrobial activity while maintaining emulsion stability, avoiding the deterioration of composition stability that occurs with higher preservative concentrations.

Inventive Principle:
Principle #35Parameter changes

3Object-affected harmful factors

If higher concentrations of preservatives are used to ensure antimicrobial efficacy, then microbial growth prevention is improved, but toxicity increases

Engineering Contradiction:
Improvemicrobial growthVSAvoidtoxicity
Core Design Contradiction:
Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The patent employs a composite preservative system comprising monoglyceryl ester of lauric acid combined with capric acid and/or its salts or edetate. This composite approach allows the achievement of effective antimicrobial activity at lower individual concentrations compared to single preservative agents. The synergistic interaction between these components provides sufficient microbial growth prevention while minimizing toxicity, as each component contributes to the overall preservative efficacy at reduced doses.

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 composition effectively prevents a no more than 10-fold increase in microbial growth of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Candida albicans for at least 24 hours, ensuring stability and safety for intravenous administration.

Implementation Method 1

a preservative system which overcomes the drawbacks of prior art compositions... effectively prevents a no more than 10-fold increase in microbial growth

Methodology Applied
Scientific EffectAntimicrobial action: Preservative

Data Source

PatentUS8759404B2Intravenous propofol emulsion compositions having preservative efficacy
Publication Date: 2014.06.24 BHARAT SERUMS & VACCINES

AI summary

The invention discloses a stable intravenous Propofol oil-in-water emulsion composition having mixed preservatives of low toxicity that is capable of withstanding accidental contamination of bacteria and fungi. The preservative system employed comprising of monoglyceryl ester of lauric acid (Monolaurin) and a member selected from (a) capric acid and/or its soluble alkaline salts or its monoglyceryl ester (Monocaprin); (b) edetate; and (c) capric acid and/or its soluble alkaline salts or its monoglyceryl ester (Monocaprin) and edetate.