Garcinol-Cyclodextrin Complex for Cardiac Dysfunction

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Solution Overview

Problem

Current chemotherapeutic agents like Doxorubicin and inotropic agents such as Isoproterenol and Digitalis cause cardiotoxicity, leading to cardiac dysfunction, and lifestyle and disease conditions like hypertension and atherosclerosis also result in reduced cardiac function, with existing treatments having significant side effects and toxicity issues.

Innovation Solution

A pharmaceutical molecule of Garcinol chemically complexed with cyclodextrins, with a mole ratio ranging from 1:1 to 1:4.5, is developed to enhance stability and bioavailability, allowing for effective management and treatment of cardiac dysfunction by improving Ca2+ handling in the sarcoplasmic reticulum and reducing oxidative stress.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If Garcinol is administered alone to treat cardiac dysfunction, then therapeutic efficacy is achieved, but toxicity increases

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Cyclodextrin serves as an intermediary carrier that complexes with Garcinol, enabling controlled delivery and reducing direct toxic effects while maintaining therapeutic efficacy. The cyclodextrin-Garcinol complex acts as a mediator between the drug and biological systems.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite material system consisting of Garcinol complexed with cyclodextrin. This composite structure combines the therapeutic properties of Garcinol with the safety and delivery advantages of cyclodextrin, achieving both efficacy and reduced toxicity.

Inventive Principle:
Principle #40Composite materials

2Quantity of substance

If extraction yield of Garcinol is increased, then more active compound is obtained, but purity decreases

Engineering Contradiction:
Improveextraction yieldVSAvoidpurity
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The invention optimizes extraction parameters including solvent composition (petroleum ether:ethyl acetate in 95:5 to 70:30 ratios), temperature, and filtration conditions to achieve the optimal balance between extraction yield and purity, obtaining 80-90% pure Garcinol at high yields.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The extraction process uses excessive solvent amounts and multiple extraction cycles to ensure maximum yield, then achieves purification through controlled precipitation and filtration steps, accepting some loss in final yield to achieve high purity.

Inventive Principle:
Principle #16Partial or excessive action

3Stability of the object's composition

If stable storage of Garcinol is achieved, then shelf life is extended, but bioavailability decreases

Engineering Contradiction:
Improvestorage stabilityVSAvoidbioavailability
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

Cyclodextrin acts as a mediator that forms an inclusion complex with Garcinol, protecting it during storage while maintaining its biological activity. The cyclodextrin cavity shields Garcinol from degradation without preventing its interaction with target enzymes.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the physical state and chemical environment of Garcinol through complexation with cyclodextrin, transforming it from an unstable free compound to a stable complex that maintains bioactivity. The mole ratio optimization (1:1 to 1:4.5) ensures both stability and bioavailability.

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 Garcinol-cyclodextrin complex effectively normalizes cardiac function parameters, reduces oxidative stress, and prevents cardiomyopathy and heart failure induced by chemotherapeutic agents and lifestyle conditions, while minimizing toxicity, thus enhancing the therapeutic index of Garcinol.

Implementation Method 1

a complex of Garcinol and Cyclodextrin, wherein mole ratio of the Garcinol to the Cyclodextrin ranges from 1:1 to 1:4.5

Methodology Applied
Scientific EffectInclusion complexation: Absorption (physical)

Data Source

PatentEP2649035B1A complex of garcinol, cyclodextrin and preparation method thereof
Publication Date: 2020.05.13 INDUS BIOTECH PVT
  • EP2649035B1 patent drawingFigure 1

AI summary

The present disclosure discloses a pharmaceutical molecule of Garcinol chemically complexed with cyclodextrins and the use of the complexed molecule in prevention and management of cardiac dysfunction induced by chemotherapy, drugs and/or other insults to the heart caused by lifestyle and disease conditions. The disclosure also relates to a method of extraction and purification of high yield of 95-99% pure Garcinol from Garcinia species and a method of chemically complexing Garcinol with cyclodextrins to improve its stability and bioavailability.