Cyclodextrin-Arteannuin Conjugate for Solubility and Bioavailability

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Solution Overview

Problem

Arteannuinoid compounds have low solubility in water, low bioavailability, and rapid elimination in human and animal models, making it difficult for them to reach therapeutic doses at cancer cell surfaces.

Innovation Solution

A cyclodextrin carrier-based arteannuinoid compound conjugate is formed through an ester bond between the carboxyl group of arteannuinoid compounds and the hydroxyl group of cyclodextrin, enhancing solubility and bioavailability by using sulfonated cyclodextrin and specific arteannuinoid compounds like artesunate, dihydroarteannuin, and arteannuin.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If arteannuinoid compounds are used as antimalarial agents, then therapeutic efficacy is achieved, but solubility in water is low

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidsolubility in water
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

Cyclodextrin serves as an intermediary carrier that forms a conjugate with arteannuinoid compounds. This carrier molecule facilitates the solubility issue by providing hydrophilic interactions while maintaining the therapeutic activity of the arteannuinoid core, thus resolving the contradiction between efficacy and solubility.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite conjugate system combining arteannuinoid compounds with cyclodextrin. This composite structure integrates the therapeutic properties of the arteannuinoid with the solubility-enhancing characteristics of the cyclodextrin carrier, achieving both therapeutic efficacy and improved water solubility simultaneously.

Inventive Principle:
Principle #40Composite materials

2Reliability

If arteannuinoid compounds are administered, then therapeutic effect is achieved, but bioavailability is low

Engineering Contradiction:
Improvetherapeutic effectVSAvoidbioavailability
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

Cyclodextrin acts as a bioavailability-enhancing intermediary that improves the absorption and delivery of arteannuinoid compounds to target sites. The conjugate formation with cyclodextrin facilitates better bioavailability while preserving the therapeutic effect, directly addressing the contradiction between therapeutic effect and bioavailability.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If arteannuinoid compounds are administered, then therapeutic effect is achieved, but elimination is rapid

Engineering Contradiction:
Improvetherapeutic effectVSAvoidduration of action
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

Cyclodextrin serves as a duration-extending intermediary that slows the elimination rate of arteannuinoid compounds. The conjugate structure reduces rapid elimination while maintaining therapeutic effect, thereby extending the duration of action and resolving the contradiction between therapeutic effect and elimination speed.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 cyclodextrin carrier-based arteannuinoid compound conjugate improves bioavailability and therapeutic efficacy, particularly for colorectal cancer cells, with enhanced solubility and targeted delivery, reducing toxic and side effects.

Implementation Method 1

A cyclodextrin carrier-based arteannuinoid compound conjugate is formed through an ester bond between the carboxyl group of arteannuinoid compounds and the hydroxyl group of cyclodextrin

Methodology Applied
Scientific EffectEster bond formation: Chemical Bonding

Data Source

PatentEP2974743B1Cyclodextrin carrier-based arteannuin compound conjugate and preparing method thereof
Publication Date: 2021.03.24 KPC PHARM INC
  • EP2974743B1 patent drawingFigure 1~2
  • EP2974743B1 patent drawingFigure 3
  • EP2974743B1 patent drawing

AI summary

Disclosed are a cyclodextrin carrier-based arteannuin compound conjugate and a preparing method thereof. Molecules of an arteannuin compound are connected by using an ester bond formed between a carboxyl group of the molecules of the arteannuin compound and a hydroxyl group of the cyclodextrin.