Catheter Locking Formulation Using Ethanol and Trimethoprim

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Solution Overview

Problem

Current catheter locking solutions fail to effectively prevent catheter occlusion and infections in central venous catheters due to issues with blood coagulation, microbial biofilm formation, and stability, leading to increased risk of infections and mortality.

Innovation Solution

A new catheter locking formulation comprising trimethoprim, EDTA calcium disodium, ethanol, propylene glycol, glycerin, and phosphate buffered saline, designed to provide fast antimicrobial activity, prevent blood coagulation, and maintain stability over a wide temperature range, while being physiologically compatible and effective against both planktonic and biofilm forms of bacteria and fungi.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If citrate and taurolidine are used in lock solution to prevent blood clotting, then anticoagulation activity is improved, but physical stability deteriorates due to precipitation at small temperature changes

Engineering Contradiction:
Improveanticoagulation activityVSAvoidphysical stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical composition parameters by replacing citrate and taurolidine with a new formulation containing 40-70% ethanol, 5-20% propylene glycol, 5-15% glycerin, and 0.5-2% trimethoprim. This parameter change resolves the contradiction by achieving anticoagulation through a different mechanism (ethanol-induced protein denaturation and membrane disruption) while maintaining physical stability across temperature ranges.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite lock solution formulation combining multiple substances (ethanol, propylene glycol, glycerin, trimethoprim, phosphate buffer) that work synergistically. The composite nature allows the solution to maintain both anticoagulation activity and physical stability, as each component contributes different properties that compensate for individual limitations.

Inventive Principle:
Principle #40Composite materials

2Reliability

If 70% ethanol is used as CLS to provide antimicrobial and anticoagulation activity, then antimicrobial efficacy is improved, but ease of operation deteriorates due to low density and viscosity

Engineering Contradiction:
Improveantimicrobial efficacyVSAvoidease of installation and maintenance
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent adjusts the ethanol concentration from 70% to 40-70% and adds co-solvents (propylene glycol and glycerin) to modify the physical parameters of the solution. This increases density and viscosity to appropriate levels for catheter locking while retaining sufficient antimicrobial efficacy through the combined action of ethanol and trimethoprim.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent formulates a composite solution where ethanol provides antimicrobial activity, while propylene glycol and glycerin contribute to improved density and viscosity. This composite approach allows the solution to meet both efficacy requirements and operational requirements simultaneously.

Inventive Principle:
Principle #40Composite materials

3Reliability

If antibiotics are used at high concentrations to eradicate biofilm, then antimicrobial activity is improved, but physical stability deteriorates due to saturation and precipitation

Engineering Contradiction:
Improveantimicrobial activityVSAvoidphysical stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent uses trimethoprim at a low concentration (0.5-2%) combined with ethanol (40-70%) to achieve biofilm eradication. This low antibiotic concentration avoids saturation and precipitation issues while the ethanol enhances penetration and antimicrobial efficacy, resolving the contradiction between activity and stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses ethanol as an intermediary substance that enhances the effectiveness of low-concentration trimethoprim. The ethanol facilitates penetration into biofilm structures and works synergistically with trimethoprim, allowing effective biofilm eradication at antibiotic concentrations that do not cause precipitation.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Reliability

If multiple substances are combined in CLS to address both occlusion and infections, then comprehensive protection is improved, but device complexity increases

Engineering Contradiction:
Improvecomprehensive protectionVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent creates a multi-functional lock solution where a single formulation addresses multiple problems: ethanol and trimethoprim provide antimicrobial activity against bacteria and fungi, while ethanol, propylene glycol, and glycerin collectively provide anticoagulation. This universal formulation eliminates the need for separate agents for different functions, reducing overall system complexity despite the presence of multiple components.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 formulation effectively prevents blood coagulation, eradicates microbial biofilms, and maintains stability, reducing the risk of catheter occlusion and infections, thereby improving patient safety and reducing healthcare costs.

Implementation Method 1

The composition comprises from about 40% to about 70% by volume ethanol, from about 5% to about 20% by weight propylene glycol, from about 5% to about 15% by weight glycerin, from about 0.5% to about 2% by weight trimethoprim

Methodology Applied
Scientific EffectAntimicrobial activity:

Implementation Method 2

The composition comprises from about 0.1% to about 5% by weight EDTA calcium disodium

Methodology Applied
Scientific EffectChelation:

Data Source

PatentEP3049123B1Catheter locking formulation and method to prepare same
Publication Date: 2020.05.13 APPELT KRZYSZTOF
  • EP3049123B1 patent drawingFigure 1A
  • EP3049123B1 patent drawingFigure 1B
  • EP3049123B1 patent drawingFigure 2

AI summary

A method to prepare a catheter locking formulation, comprising in a first step, dissolving trimethoprim in propylene glycol at a temperature greater than room temperature, and in a final step, adding absolute ethanol at about room temperature to a solution of trimethoprim, propylene glycol, EDTA Calcium Disodium Hydrate, phosphate buffered saline, and glycerin.