Propofol Ketamine Emulsion Stability and Pain Reduction

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Solution Overview

Problem

Current formulations of Propofol and Ketamine combinations for procedural sedation and analgesia lack stability and compatibility data, leading to potential adverse effects and pain during administration, with existing emulsions being cloudy and not fully addressing impurity profiles.

Innovation Solution

A stable injectable emulsion of Propofol and Ketamine is developed, using a combination of Propofol, Ketamine, a chelating agent (disodium EDTA), a solubilizer (glycerol), and a pH adjuster (sodium hydroxide) in water, with purified lecithin as an emulsifier, to create a clear, stable, and pain-reducing formulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If Propofol and Ketamine are combined in existing emulsion formulations, then sedation efficacy is improved, but stability and compatibility are compromised leading to cloudiness and potential adverse effects

Engineering Contradiction:
Improvesedation efficacyVSAvoidemulsion stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent optimizes the concentration parameters of emulsifiers (lecithin 1.2-2.4%, soybean oil 10-20%), chelating agents (EDTA 0.1-0.5%), and pH adjusters (sodium hydroxide to maintain pH 7.0-8.5) to achieve both stability and efficacy. By carefully controlling these parameters, the formulation maintains clarity and stability while providing effective sedation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite emulsion system combining multiple components: Propofol (0.5-2.0%), Ketamine (5-20%), lecithin as emulsifier, soybean oil as co-emulsifier, EDTA as chelating agent, and sodium hydroxide as pH adjuster. This composite formulation synergistically addresses stability, compatibility, and therapeutic efficacy simultaneously.

Inventive Principle:
Principle #40Composite materials

2Reliability

If Propofol is administered alone, then sedation is achieved, but injection pain and adverse effects increase

Engineering Contradiction:
Improvesedation efficacyVSAvoidinjection pain
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent merges Propofol with Ketamine in a single emulsion formulation. Ketamine (5-20%) provides analgesic and anti-nociceptive properties that counteract the injection pain caused by Propofol, while both agents work synergistically to enhance sedation efficacy and reduce adverse effects.

Inventive Principle:
Principle #5Merging (Combining)

3Quantity of substance

If conventional emulsion formulations are used, then Propofol delivery is achieved, but cloudiness and impurity accumulation occur

Engineering Contradiction:
ImprovePropofol deliveryVSAvoidemulsion clarity
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent introduces EDTA (0.1-0.5%) as a chelating agent intermediary that binds metal ions which could catalyze oxidation of Propofol. This prevents formation of quinone impurities and maintains emulsion clarity. Sodium hydroxide is used as another intermediary to precisely control pH at 7.0-8.5, optimizing both stability and Propofol delivery.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 emulsion provides therapeutic stability and reduces injection pain, minimizing adverse cardio-respiratory effects and psychic disturbances, while maintaining sedation efficacy with reduced doses, resulting in a safer and more effective anesthetic combination.

Implementation Method 1

stable injectable emulsion of Propofol and Ketamine in combination... with purified lecithin as an emulsifier

Methodology Applied
Scientific EffectEmulsion: Emulsion

Implementation Method 2

purified lecithin as an emulsifier

Methodology Applied
Scientific EffectSurfactant: Surfactant

Implementation Method 3

Chelating agent... disodium EDTA

Methodology Applied
Scientific EffectChelation:

Implementation Method 4

pH adjuster with water as principle solvent... sodium hydroxide to adjust the pH

Methodology Applied
Scientific EffectpH adjustment:

Implementation Method 5

solubilizer (glycerol)... 2.25% glycerol as a tonicity-adjusting agent

Methodology Applied
Scientific EffectSolubilization: Solvation

Data Source

PatentUS10821087B2Stabilized injectable emulsion of Propofol and Ketamine
Publication Date: 2020.11.03 NEON LAB

AI summary

Disclosed herein is stable injectable emulsion of Propofol and Ketamine in combination; a base to adjust the pH and purified Lecithin.