Uridine and Pyruvate Mitigate Antibiotic Side Effects

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Solution Overview

Problem

Antibiotics often cause adverse side effects due to interference with cellular and mitochondrial metabolism, leading to energy synthesis issues and cell cycle arrest, particularly in fast-dividing cells, which can result in severe conditions like the Gray Baby Syndrome and bone marrow damage.

Innovation Solution

A pharmaceutical composition comprising a therapeutically effective amount of an antibiotic combined with uridine and pyruvate compounds, which support cellular energy generation and nucleic acid synthesis, thereby mitigating the side effects without interfering with the antibiotic's efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotics are administered to treat bacterial infections, then the antibiotic effectiveness is improved, but adverse side effects worsen due to interference with cellular and mitochondrial metabolism

Engineering Contradiction:

Improveantibiotic effectivenessVSAvoidadverse side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Uridine and pyruvate compounds serve as intermediary substances that mediate between the antibiotic treatment and cellular metabolism. These compounds provide alternative pathways for energy production and nucleic acid synthesis, protecting mitochondrial function while allowing antibiotics to maintain their antibacterial activity. The intermediaries buffer the harmful metabolic interference caused by antibiotics.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the metabolic parameters of the cell by supplementing with uridine and pyruvate. This alters the cellular energy metabolism from relying solely on mitochondrial oxidative phosphorylation (which is inhibited by antibiotics) to utilizing glycolysis and alternative pathways that are supported by the supplemented compounds, thereby reducing side effects while maintaining treatment efficacy.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If antibiotics interfere with mitochondrial protein synthesis, then bacterial protein synthesis is inhibited, but cellular energy synthesis deteriorates due to shifted metabolic pathways

Engineering Contradiction:

Improveprotein synthesis inhibitionVSAvoidenergy synthesis

Core Design Contradiction:

ReliabilityVSUse of energy by moving object

Solution Approach 1:

The supplemented uridine and pyruvate enable the cell to serve itself by providing alternative metabolic substrates. When mitochondrial protein synthesis is inhibited, the cell can still produce energy through glycolysis supported by pyruvate and maintain nucleic acid synthesis through uridine supplementation, allowing self-sustenance despite antibiotic interference with mitochondrial function.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

Uridine and pyruvate act as intermediary substrates that bridge the gap caused by mitochondrial dysfunction. They provide alternative routes for energy production and biomolecule synthesis, mediating the metabolic shift from mitochondrial-dependent pathways to cytosolic pathways that can operate under antibiotic pressure.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If antibiotics cause cell cycle arrest in fast-dividing cells, then bacterial growth is prevented, but mammalian cell proliferation is impaired leading to severe side effects

Engineering Contradiction:

Improvebacterial growth preventionVSAvoidcell proliferation

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The uridine and pyruvate supplementation provides beforehand cushioning for fast-dividing mammalian cells before they encounter antibiotic-induced metabolic stress. By pre-supplementing these compounds, the cells are prepared to maintain their proliferation capacity even when antibiotics interfere with mitochondrial function, preventing cell cycle arrest and severe side effects like bone marrow damage.

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

Data Source

PatentEP3027213B1Compositions for ameliorating and/or preventing adverse side effects in antibiotic therapy

Publication Date: 2017.10.18 MITOGENOMIX

AI summary

The present invention relates to a pharmaceutical composition comprising: (i) a therapeutically effective amount of at least one antibiotic; and (ii) a therapeutically effective amount of both an uridine and pyruvate compound. The formulation is prepared in a suitable dosage form for the delivery of antibiotics and the reduction of the known adverse side-effects of the antibiotics is achieved by the added uridine and pyruvate compounds when administered to a subject. The present invention neutralizes highly efficient these side-effects without interfering with the antibiotic effect of the drugs. By co-administration of antibiotics and uridine and pyruvate compounds, cell's capability to generate energy and synthesize nucleic acids is being supported. Especially side-effects caused by antibiotics that interfere with the cellular and mitochondrial metabolism are effectively removed as secondary actions of the drugs. Also included are methods of reducing or preventing a failure of treatment for an antibiotic-treatable infection in a patient comprising administering the formulation in a suitable way of administration.