Resuscitation Composition Using Cyclodextrin for Hemorrhagic Shock

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Solution Overview

Problem

Current treatments for hemorrhagic shock, particularly those involving melatonin and D-beta-hydroxybutyrate, face challenges such as the use of dimethyl sulfoxide (DMSO), which has an unknown safety profile in humans and can cause hemolysis, and require complex reconstitution processes, making them unsuitable for immediate use in emergency settings.

Innovation Solution

A resuscitation composition comprising melatonin, D-beta-hydroxybutyrate, hydroxypropyl-beta-cyclodextrin, polyvinylpyrrolidone, and polyethylene glycol, formulated to be easily reconstituted and administered, replacing DMSO with safer components like hydroxypropyl-beta-cyclodextrin and polyvinylpyrrolidone to enhance solubility and stability, allowing for quick administration in emergency situations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If dimethyl sulfoxide (DMSO) is used as a solvent for melatonin and D-beta-hydroxybutyrate, then the solubility and stability of the composition are improved, but the safety profile deteriorates due to unknown human safety and potential hemolysis

Engineering Contradiction:

ImprovestabilityVSAvoidhemolysis

Core Design Contradiction:

Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent removes DMSO from the formulation entirely and replaces it with a combination of hydroxypropyl-beta-cyclodextrin, polyvinylpyrrolidone, and polyethylene glycol. This extraction of the harmful solvent while maintaining the solubility and stability functions through alternative excipients directly resolves the contradiction between composition stability and safety.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces hydroxypropyl-beta-cyclodextrin as an intermediary substance that forms inclusion complexes with melatonin and D-beta-hydroxybutyrate, enabling solubility enhancement without using DMSO. This intermediary approach maintains the beneficial solubility properties while eliminating the harmful effects of DMSO.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Stability of the object's composition

If a complex reconstitution process is used for the resuscitation composition, then the stability and solubility of the active ingredients are improved, but the ease of operation deteriorates making it unsuitable for emergency settings

Engineering Contradiction:

ImprovestabilityVSAvoidease of administration

Core Design Contradiction:

Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent pre-formulates the resuscitation composition in a stable, lyophilized state containing all necessary excipients (hydroxypropyl-beta-cyclodextrin, polyvinylpyrrolidone, polyethylene glycol) that maintain solubility and stability. This preliminary preparation allows the composition to be stored in a stable form and then quickly reconstituted with simple addition of sterile water, eliminating complex reconstitution steps while maintaining stability.

Inventive Principle:

Principle #10Preliminary action

3Ease of operation

If the volume of resuscitation composition is reduced for rapid administration, then the ease of operation is improved, but the quantity of substance deteriorates potentially reducing therapeutic efficacy

Engineering Contradiction:

Improveease of administrationVSAvoidvolume

Core Design Contradiction:

Ease of operationVSQuantity of substance

Solution Approach 1:

The patent concentrates the active ingredients (melatonin and D-beta-hydroxybutyrate) to high concentrations within the formulation, utilizing the solubility-enhancing properties of hydroxypropyl-beta-cyclodextrin and polyvinylpyrrolidone. This parameter change in concentration allows delivery of therapeutically effective doses in small volumes (e.g., 1-10 mL), achieving both rapid administration and adequate substance quantity.

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

The composition effectively increases survival rates in hemorrhagic shock models by providing a stable, easily reconstituted, and safe formulation that avoids adverse effects like hemolysis, improving tissue perfusion and metabolic support during critical blood loss.

Implementation Method 1

replacing DMSO with safer components like hydroxypropyl-beta-cyclodextrin and polyvinylpyrrolidone to enhance solubility

Methodology Applied

Scientific EffectSolubility enhancement: Solvation

Implementation Method 2

D-beta-hydroxybutyrate, formulated to be easily reconstituted and administered, replacing DMSO with safer components

Methodology Applied

Scientific EffectMetabolic support:

Data Source

PatentUS10307398B2Resuscitation composition and methods of making and using

Publication Date: 2019.06.04 REGENTS OF THE UNIVERSITY OF MINNESOTA

AI summary

A resuscitation composition is described herein, as are methods of making and using such a composition.