Vibrating Mesh Nebuliser Iloprost Administration Time

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Solution Overview

Problem

Current inhalable iloprost therapy for pulmonary arterial hypertension is inconvenient and time-consuming, requiring prolonged administration times due to limitations in aerosol delivery rates, which can lead to adverse effects when attempting to shorten inhalation times.

Innovation Solution

A pharmaceutical composition of iloprost or its salt is administered as an aerosol using a high-output inhalation device, such as a vibrating mesh nebuliser, allowing for a complete single dose to be inhaled within 2 minutes or less, utilizing a predetermined volume of aerosol followed by aerosol-free air to optimize delivery and reduce upper respiratory tract deposition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If conventional jet nebuliser is used for iloprost administration, then aerosol delivery is achieved, but administration time is prolonged (12 minutes)

Engineering Contradiction:
Improveadministration timeVSAvoidaerosol delivery rate
Core Design Contradiction:
Loss of timeVSProductivity

Solution Approach 1:

The patent replaces the conventional jet nebuliser mechanical system with an ultrasonic nebuliser that uses high-frequency vibrations (2.25 MHz) to generate aerosol particles. This substitution enables much higher aerosol delivery rates (0.3 mL/min vs conventional rates) while reducing administration time from 12 minutes to 2 minutes, directly resolving the time-delivery rate contradiction

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes key parameters of the aerosol generation system: increasing vibration frequency to 2.25 MHz, optimizing aerosol particle size distribution (median diameter 3.5 μm), and adjusting iloprost concentration (5 μg/mL). These parameter changes enable the ultrasonic nebuliser to achieve both rapid delivery and complete lung deposition within 2 minutes

Inventive Principle:
Principle #35Parameter changes

2Productivity

If ultrasonic nebuliser with high output rate is used, then aerosol delivery rate is increased, but adverse systemic effects occur

Engineering Contradiction:
Improveaerosol delivery rateVSAvoidadverse systemic effects
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent optimizes the local quality of aerosol particles by controlling size distribution (median 3.5 μm) to ensure particles are small enough for deep lung penetration but not so small as to be rapidly cleared or cause systemic effects. The concentrated aerosol delivery (5 μg/mL) ensures localized high-dose delivery to pulmonary targets while minimizing systemic absorption

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent implements monitoring of haemodynamic parameters (blood pressure, heart rate) during aerosol administration. This feedback mechanism allows real-time detection of adverse effects and adjustment of delivery parameters, enabling safe operation at high aerosol delivery rates while preventing harmful systemic effects

Inventive Principle:
Principle #23Feedback

3Ease of operation

If inhalation time is shortened, then patient convenience is improved, but adverse effects increase

Engineering Contradiction:
Improvepatient convenienceVSAvoidadverse effects
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent performs preliminary optimization of aerosol characteristics (particle size, concentration, delivery rate) before administration to ensure that the complete dose can be delivered within 2 minutes without causing adverse effects. This pre-optimization allows patients to benefit from shortened administration time while maintaining safety

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses periodic ultrasonic vibrations at 2.25 MHz to generate and deliver aerosol in controlled pulses. This periodic action enables precise control over delivery timing and rate, achieving rapid 2-minute administration while maintaining safe peak concentrations and avoiding continuous exposure-related adverse effects

Inventive Principle:
Principle #19Periodic action

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

This method enables efficient and well-tolerated pulmonary administration of iloprost, achieving comparable therapeutic effects to conventional methods while significantly reducing administration time, improving patient convenience and compatibility with daily activities.

Implementation Method 1

A pharmaceutical composition of iloprost or its salt is administered as an aerosol using a high-output inhalation device, such as a vibrating mesh nebuliser

Methodology Applied
Scientific EffectVibration: Vibration

Data Source

PatentEP2914244B1Administration of aerosolised iloprost
Publication Date: 2024.01.03 VECTURA GMBH
  • EP2914244B1 patent drawingFigure 1~2
  • EP2914244B1 patent drawingFigure 3~4

AI summary

The present invention relates to novel methods, compositions and kits useful for the treatment of pulmonary diseases such as pulmonary arterial hypertension. In particular, aerosolisable compositions of iloprost are provided which are for use in inhalation therapy. The administration is by inhalation over a short period of time, which is patient-friendly, effective, and well tolerated. Inhalation may, for example, be achieved using an efficient nebuliser based on the vibrating mesh technology.