SGLT2 Inhibitors Sustaining Beta-Hydroxybutyrate Levels

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Solution Overview

Problem

Current treatments for aortic aneurysms and dissections are ineffective in preventing disease progression, and existing methods to elevate beta-hydroxybutyrate (BHB) levels do not sustain therapeutic concentrations for extended periods.

Innovation Solution

The use of SGLT2 inhibitors alone or in combination with exogenous ketones, specifically beta-hydroxybutyrate (BHB), to achieve sustained therapeutic levels of BHB, which has anti-inflammatory and epigenetic effects beneficial for treating aortic aneurysms and other conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If existing methods to elevate BHB levels are used, then BHB concentration increases, but the elevation is not sustained for extended periods

Engineering Contradiction:
Improveduration of therapeutic BHB elevationVSAvoidconsistency of therapeutic BHB levels
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The patent employs SGLT2 inhibitors as intermediary compounds that indirectly elevate and sustain BHB levels. Rather than administering BHB directly (which has short half-life), the SGLT2 inhibitor acts as a mediator that blocks BHB reabsorption in the kidneys, creating sustained endogenous production and circulation of BHB throughout the day.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The body's own metabolic system is harnessed to maintain therapeutic BHB levels. By inhibiting the SGLT2 transporter, the body naturally produces and circulates BHB without requiring external supplementation. The system uses the body's existing ketone production mechanisms, redirected to maintain elevated circulating levels through renal excretion blockade.

Inventive Principle:
Principle #25Self-service

2Duration of action of moving object

If SGLT2 inhibitors are used to sustain BHB levels, then therapeutic duration is extended, but the mechanism involves renal excretion which may have side effects

Engineering Contradiction:
Improveduration of therapeutic BHB elevationVSAvoidrenal side effects
Core Design Contradiction:
Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent leverages the dose-dependent effects of SGLT2 inhibitors to achieve therapeutic BHB elevation while minimizing side effects. By optimizing the dosage to achieve moderate BHB levels (0.5-3.0 mM) rather than extreme ketosis, the treatment sustains therapeutic benefits while reducing the likelihood of renal and other adverse effects associated with higher doses.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If high doses of BHB are administered to achieve therapeutic levels, then efficacy increases, but compliance and safety decrease

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidpatient compliance
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent utilizes a once-daily oral medication (SGLT2 inhibitor) that provides sustained BHB elevation without requiring patients to administer multiple doses or undergo complex regimens. The single daily dose is convenient, affordable, and maintains therapeutic levels throughout the day, significantly improving compliance compared to requiring multiple BHB supplements or dietary restrictions.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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

Sustained elevation of BHB levels using SGLT2 inhibitors and exogenous ketones effectively reduces inflammation, promotes vascular health, and provides therapeutic benefits for aortic aneurysms, heart failure, and other conditions.

Implementation Method 1

The use of SGLT2 inhibitors alone or in combination with exogenous ketones, specifically beta-hydroxybutyrate (BHB), to achieve sustained therapeutic levels of BHB

Methodology Applied
Scientific EffectSGLT2 inhibition:

Implementation Method 2

The use of SGLT2 inhibitors alone or in combination with exogenous ketones, specifically beta-hydroxybutyrate (BHB), to achieve sustained therapeutic levels of BHB

Methodology Applied
Scientific EffectAbsorption: Absorption (physical)

Implementation Method 3

which has anti-inflammatory and epigenetic effects beneficial for treating aortic aneurysms and other conditions

Methodology Applied
Scientific EffectAnti-inflammatory signaling:

Implementation Method 4

which has anti-inflammatory and epigenetic effects beneficial for treating aortic aneurysms and other conditions

Methodology Applied
Scientific EffectEpigenetic modulation:

Data Source

PatentEP4566598A1Compositions providing SGLT2i and BHB activity and methods of use to treat human disease
Publication Date: 2025.06.11 ZOSALA PHARMA INC
  • EP4566598A1 patent drawingFigure 1
  • EP4566598A1 patent drawingFigure 2
  • EP4566598A1 patent drawingFigure 3

AI summary

Compositions of compounds with SGLT2i activity in combination with compounds having BHB activity. These can be used in methods of treatment for a variety of human diseases such as cognitive deficits, Alzheimer's, kidney disease, heart failure and aortic aneurysms and dissection. The methods allow therapeutic levels of both SGLT2i and BHB activity to be achieved and maintained for as many hours per day as deemed optimal for the patient in need of therapy.