Renal Denervation via Local pH Modulation

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Solution Overview

Problem

Current methods fail to effectively modulate local tissue physiology to enhance drug uptake and therapeutic efficacy in targeted tissues, particularly for treating conditions like hypertension and heart failure, by altering pH and osmolarity around nerves.

Innovation Solution

A pharmaceutical preparation comprising guanethidine monosulfate or hemisulfate, delivered in a liquid, gel, or semisolid form, is administered to modulate local tissue pH and osmolarity, using ethanol and alkaline buffers to create a therapeutic environment that enhances cellular uptake and efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional drug delivery methods are used, then drug administration is simple, but cellular uptake and therapeutic efficacy are insufficient

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoiddelivery system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes the pH parameter of the delivery vehicle to alkaline conditions (pH 8-11), which alters membrane permeability and polarization of the pharmaceutical agent, thereby enhancing cellular uptake and therapeutic efficacy without requiring complex delivery devices

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a localized alkaline environment at the target tissue site using pH-modulating compositions, which selectively enhances drug uptake in the intended region while maintaining normal physiological conditions elsewhere in the body

Inventive Principle:
Principle #3Local quality

2Quantity of substance

If pH-modulating compositions are administered, then cellular uptake is enhanced, but tissue physiology is altered

Engineering Contradiction:
Improvedrug uptakeVSAvoidtissue physiology
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent applies pH-modulating compositions before administering the pharmaceutical agent, preparing the target tissue by altering its pH and osmolarity to facilitate enhanced drug uptake, then allowing the tissue to return to normal physiology afterward

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses pH-modulating compositions as intermediary agents that temporarily alter tissue conditions to enable enhanced drug delivery, after which the intermediary is removed or metabolized and tissue physiology returns to normal

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

This approach enables more effective denervation of renal nerves, reducing blood pressure, improving heart failure symptoms, and treating insulin resistance and sleep apnea by optimizing drug delivery and tissue interaction.

Implementation Method 1

the preparation modulates local tonicity or osmolarity of the tissue to achieve enhanced cellular uptake of the pharmaceutical agent by said tissue

Methodology Applied
Scientific EffectOsmosis: Osmosis

Implementation Method 2

the preparation modulates local tonicity or osmolarity of the tissue... wherein the liquid, gel, or semisolid comprises ethanol and the pharmaceutical agent comprises guanethidine monosulfate

Methodology Applied
Scientific EffectBuffering:

Data Source

PatentEP3556749B1Localized modulation of tissues and cells to enhance therapeutic effects including renal denervation
Publication Date: 2023.10.04 MERCATOR MEDSYSTEMS INC
  • EP3556749B1 patent drawingFigure 1A~1C
  • EP3556749B1 patent drawingFigure 2A~2B
  • EP3556749B1 patent drawingFigure 3

AI summary

Pharmaceutical preparations, compositions, systems, and devices including medical devices and diagnostic or therapeutic agents, and methods to treat disease by modification of local tissue environment to modulate the therapeutic index of locally or systemically delivered therapeutic or diagnostic agents. Improved ability to reduce sysmpathetic nerve activity in the adventitia and perivascular tissues around arteries and veins in the body. Modulation of the local tissue environment around an artery to enable more effective denervation with or without a therapeutic agent. Modulation may include adjustment of the pH of the tissue.