Artemether Injection Stability via Low-Temperature Micronization

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Solution Overview

Problem

Current treatments for leukemia lack effective and non-toxic options with minimal side effects, as existing therapies often result in drug tolerance and significant harm to normal cells.

Innovation Solution

Artemether, combined with a water-soluble cyclodextrin derivative in a specific weight ratio, is formulated into an injection or lyophilized powder for injection, using micronization technology at low temperatures to maintain stability and enhance dissolution, thereby inhibiting leukemia cell growth with minimal toxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If conventional pulverization technique is used to prepare artemether, then the drug can be processed, but local excessive temperatures cause degradation of artemether

Engineering Contradiction:
Improvedrug processingVSAvoidartemether stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent changes the temperature parameter from conventional room temperature pulverization to low temperature (0°C-10°C) pulverization. This parameter change prevents local excessive temperatures that would degrade artemether, while still allowing the drug to be processed into fine particles for injection formulation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces water-soluble cyclodextrin derivatives as intermediary substances that form inclusion complexes with artemether. This mediator protects artemether from degradation during processing and enhances its water solubility, enabling injection formulation without direct exposure to degrading conditions.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If existing leukemia therapies are used, then treatment can be provided, but drug tolerance develops and significant harm is caused to normal cells

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidtoxicity to normal cells
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies the local quality principle by using cyclodextrin derivatives to create a localized delivery system. The inclusion complex provides targeted protection and release of artemether, concentrating the therapeutic effect on leukemia cells while minimizing exposure and damage to normal cells, thereby reducing overall toxicity.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent creates a composite material system consisting of artemether encapsulated within water-soluble cyclodextrin derivatives. This composite structure combines the antitumor properties of artemether with the protective and solubilizing characteristics of cyclodextrins, enabling effective leukemia treatment with reduced side effects and drug tolerance.

Inventive Principle:
Principle #40Composite materials

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

Artemether demonstrates significant inhibition of leukemia cell growth in nude mice models, achieving inhibition ratios of 60-80% with minimal toxicity, comparable to cyclophosphamide, indicating its potential as a new anti-tumor drug.

Implementation Method 1

artemether is added into an aqueous solution of a water-soluble cyclodextrin derivative at 50℃-90℃, stirred to dissolve artemether

Methodology Applied
Scientific EffectInclusion complex formation: Solvation

Implementation Method 2

artemether is pulverized in a low-temperature pulverizer at 0℃-10℃

Methodology Applied
Scientific EffectMechanical pulverization: Abrasion

Implementation Method 3

treated or lyophilized according to a conventional process of an injection to obtain a finished product

Methodology Applied
Scientific EffectFreeze drying: Freeze Drying

Data Source

PatentEP2926812B1Use of artemether in preparation of drug for treating leukemia
Publication Date: 2019.03.06 KPC PHARM INC
  • EP2926812B1 patent drawingFigure 1~2
  • EP2926812B1 patent drawingFigure 3~4
  • EP2926812B1 patent drawingFigure 5~6

AI summary

Disclosed is a use of artemether in the preparation of a drug for treating leukemia. The drug is an artemether injection or lyophilized powder for injection, and is prepared with the artemether and a water soluble cyclodextrin derivative in a weight ratio of 1:30-70.