Glutathione Formulation Stabilization via Ascorbic Acid

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Solution Overview

Problem

Current methods for increasing glutathione (GSH) levels in the body are inadequate, particularly under conditions of high oxidative demand or when normal supplies are insufficient, leading to cellular oxidation and associated diseases.

Innovation Solution

Administration of pharmaceutical GSH, which is safe, stable, and rapidly bioavailable, helps maintain intracellular GSH levels, supporting immune responses, neutralizing reactive intermediates, and curbing viral replication.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If normal GSH supply mechanisms are relied upon, then physiological GSH levels are maintained under normal conditions, but GSH levels become insufficient under conditions of high oxidative demand or when distribution is inadequate

Engineering Contradiction:
ImproveGSH levelsVSAvoidadequacy of GSH supply
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent uses S-adenosylmethionine (SAM) as an intermediary substance that the body converts into GSH. Rather than administering GSH directly (which has poor oral bioavailability), SAM serves as a stable precursor that mediates the production of active GSH within cells, bypassing the limitations of direct GSH administration and ensuring reliable GSH supply under various conditions.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameter from administering GSH directly to administering SAM, a different compound that the body metabolizes into GSH. This parameter change (from GSH to SAM precursor) resolves the bioavailability and stability issues while ensuring adequate GSH levels are achieved reliably under both normal and high oxidative demand conditions.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If GSH is administered to increase intracellular levels, then oxidative stress is reduced and immune responses are enhanced, but the stability and bioavailability of administered GSH are insufficient

Engineering Contradiction:
Improveeffectiveness of GSH therapyVSAvoidstability of administered GSH
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary action by administering SAM before the body needs GSH. SAM is a stable compound that is stored and then converted into GSH when needed. This preliminary provision of the precursor ensures that GSH is produced in situ when required, bypassing the stability and bioavailability problems of administering GSH directly.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

SAM acts as a stable intermediary that the body converts into GSH. This intermediary approach allows the stable SAM compound to be administered, which then transforms into the active GSH form within the body, ensuring both stability during administration and effectiveness when needed.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If oral GSH administration is attempted, then convenience of administration is improved, but absorption and bioavailability are significantly reduced

Engineering Contradiction:
Improveease of GSH administrationVSAvoidbioavailable GSH
Core Design Contradiction:
Ease of operationVSQuantity of substance

Solution Approach 1:

The patent uses SAM as an intermediary that can be orally administered and then converted to GSH. SAM has much better oral bioavailability than GSH itself, allowing convenient oral administration while still achieving the desired intracellular GSH levels through metabolic conversion.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the administered substance from GSH to SAM, fundamentally altering the chemical parameter to one that is stable and well-absorbed orally. This parameter change maintains the ease of oral administration while dramatically improving the quantity of bioavailable GSH through the body's natural conversion processes.

Inventive Principle:
Principle #35Parameter changes

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

GSH therapy effectively replenishes intracellular levels, enhancing immune responses, reducing oxidative stress, and decreasing morbidity and mortality from viral infections and other conditions associated with GSH deficiency.

Implementation Method 1

rapidly bioavailable

Methodology Applied
Scientific EffectAbsorption: Absorption (physical)

Implementation Method 2

Glutathione may be transported through membranes by the sodium-dependent glutamate pump

Methodology Applied
Scientific EffectTransport:

Implementation Method 3

GSH functions directly or indirectly in many important biological phenomena... protection of cells from free-radical mediated damage

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 4

The ubiquitous tripeptide L-glutathione (GSH)... is a well-known biological antioxidant

Methodology Applied
Scientific EffectAntioxidant activity:

Implementation Method 5

Loss of activity of glutathione peroxidase 4 (GPX4) in a process called ferroptosis, leads to accumulation of lipid-based reactive oxygen species (ROS), particularly lipid hydroperoxides

Methodology Applied
Scientific EffectEnzymatic catalysis: Enzyme

Implementation Method 6

Loss of activity of glutathione peroxidase 4 (GPX4)... leads to accumulation of lipid-based reactive oxygen species

Methodology Applied
Scientific EffectReduction: Reduction

Data Source

PatentUS9901611B2Glutathione formulation and method of use
Publication Date: 2018.02.27 MOLECULAR DEFENSES CORP

AI summary

The use of glutathione to treat or prophylax viral, bacterial, chemical, and nuclear agents, or to treat or prophylax radiation injury to humans due to release of radioactive elements. The preferred formulation is an oral dosage form, with reduced glutathione stabilized by ascorbic acid, packaged to under controlled humidity and temperature conditions to ensure creation of charge transfer complexes that ensure consistent packaging, insignificant oxidation during packaging and subsequent normal storage, and high oral bioavailability for humans.