Splenic Arterial Nerve Stimulation to Reduce Off-Target Effects

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Solution Overview

Problem

Existing methods of electrical stimulation of the splenic nerves for treating inflammatory disorders can lead to off-target effects such as changes in splenic artery and vein blood flow, systemic arterial blood pressure, and heart rate, necessitating improved stimulation parameters and electrode designs to minimize these effects while maximizing immunesuppressive effects.

Innovation Solution

Optimized electrical stimulation parameters, including frequencies ≤300 Hz for burst patterns or ≤50 Hz for continuous application, combined with specific electrode designs, are used to stimulate the splenic arterial nerve, utilizing neurophysiological characteristics to determine optimal patterns that increase immunesuppressive effects while reducing systemic effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If electrical stimulation parameters are optimized to maximize immunesuppressive effects, then therapeutic efficacy is improved, but off-target effects such as changes in blood flow, blood pressure, and heart rate increase

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidoff-target effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies periodic burst stimulation patterns rather than continuous stimulation. The electrical signal is delivered in bursts of 10-100 pulses at frequencies of 1-100 Hz, with intervals between bursts. This periodic action allows the system to achieve therapeutic immune modulation while minimizing cumulative off-target effects on cardiovascular function, as the stimulation is not continuously applied.

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The patent optimizes multiple electrical parameters including frequency (1-100 Hz), pulse width (10-1000 μs), and burst pattern (10-100 pulses per burst) to achieve the desired therapeutic effect. By carefully adjusting these parameters, the system can stimulate the splenic nerve effectively for immune modulation while staying below thresholds that cause harmful off-target effects on blood flow and blood pressure.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If stimulation frequency is increased to enhance neural activity, then immunesuppressive effects are improved, but systemic effects such as changes in blood pressure and heart rate worsen

Engineering Contradiction:

Improveimmunesuppressive effectsVSAvoidsystemic effects

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent uses periodic burst patterns where stimulation is applied in discrete bursts of 10-100 pulses at frequencies of 1-100 Hz, followed by rest intervals. This allows the system to achieve significant immunesuppressive effects through repeated neural activation while preventing continuous systemic stress responses that would occur with continuous high-frequency stimulation.

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The patent maintains continuous therapeutic action through overlapping burst patterns. By delivering bursts at intervals that ensure immune system modulation continues effectively, while using low enough frequencies within bursts to avoid excessive systemic effects, the system achieves continuous immunesuppression without harmful cumulative systemic responses.

Inventive Principle:

Principle #20Continuity of useful action

3Reliability

If electrical signal amplitude is increased to improve neural stimulation, then therapeutic effect is enhanced, but risk of tissue damage and off-target effects increases

Engineering Contradiction:

Improveneural stimulation effectivenessVSAvoidtissue damage risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent optimizes the electrical signal parameters including pulse width (10-1000 μs), frequency (1-100 Hz), and amplitude to achieve effective neural stimulation of the splenic nerve. By carefully controlling these parameters, the system generates sufficient current to activate immune-modulating neural pathways while remaining below the threshold for causing tissue damage or harmful off-target effects.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The use of periodic burst patterns allows the system to deliver adequate current amplitude for effective neural stimulation during each burst, while the rest intervals between bursts prevent cumulative tissue damage. The periodic nature distributes the total energy delivery over time, achieving therapeutic effectiveness without exceeding safety thresholds.

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

The optimized stimulation parameters and electrode designs effectively stimulate neural activity in the splenic arterial nerve, reducing off-target effects and maintaining therapeutic efficacy for inflammatory disorders.

Implementation Method 1

at least one controller configured to control the operation of the least one electrode to apply an electrical signal to the nerve

Methodology Applied

Scientific EffectElectrical stimulation: Electric Field

Data Source

PatentUS20250235702A1Stimulation of a nerve supplying the spleen

Publication Date: 2025.07.24 GALVANI BIOELECTRONICS LTD

AI summary

Stimulation of neural activity in a nerve supplying the spleen, wherein the nerve is associated with a neurovascular bundle, can modulate pro-and anti-inflammatory molecules levels, thereby reducing inflammation and providing ways of treating inflammatory disorders. The invention provides improved ways of treating inflammatory disorders which minimize off-target effects.