Lipoplex Production via Ethanol Solvation and Lyophilization

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Solution Overview

Problem

Conventional lipoplex production methods require complex processes involving organic solvents like chloroform or cyclohexane, necessitating large-scale facilities and extensive labor, and are not suitable for efficient production in hospital settings.

Innovation Solution

A method for producing lyophilized lipoplex powders by dissolving dioleylphosphatidylethanolamine, phosphatidylcholine, and a cationic lipid in ethanol, then adding the alcohol solution to RNAi molecules with agitation and lyophilizing, allowing for easy reconstitution in water, eliminating the need for organic solvents and reducing labor-intensive processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional methods using organic solvents like chloroform or cyclohexane are used for lipoplex production, then the lipoplex can be produced with established formulations, but the process requires large-scale facilities for hazardous material handling and extensive labor

Engineering Contradiction:
Improvelipoplex production reliabilityVSAvoidfacility complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and eliminates the hazardous organic solvents (chloroform, cyclohexane) from the lipoplex production process, replacing them with water-soluble surfactants. This removes the need for specialized hazardous material handling facilities while maintaining production reliability through the use of biocompatible excipients

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the chemical parameters of the production system by substituting organic solvents with aqueous surfactant solutions. This parameter change transforms the process from one requiring explosion-proof facilities to one that can be conducted in standard pharmaceutical manufacturing environments

Inventive Principle:
Principle #35Parameter changes

2Reliability

If conventional lipoplex production methods are used, then the lipoplex can be produced with proven formulations, but the process requires extensive labor and complicated procedures

Engineering Contradiction:
Improvelipoplex production reliabilityVSAvoidmanufacturing ease
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent removes the labor-intensive steps of organic solvent handling, phase separation, and extensive purification procedures by using water-soluble surfactants that allow direct aqueous formulation and simplified processing

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the physical-chemical parameters of the formulation system to use aqueous surfactant-based excipients, which fundamentally simplifies the manufacturing process by eliminating complex solvent removal and purification steps while maintaining product reliability

Inventive Principle:
Principle #35Parameter changes

3Productivity

If organic solvents like chloroform or cyclohexane are used in lipoplex production, then the lipoplex can be produced with established methods, but hazardous material handling facilities are required

Engineering Contradiction:
Improvelipoplex production efficiencyVSAvoidhazardous solvent handling requirements
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the potential harm of using solvents by replacing hazardous organic solvents with benign aqueous surfactant solutions. This eliminates the need for hazardous material facilities while maintaining production efficiency through the use of biocompatible, water-soluble excipients that simplify rather than complicate the process

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

4Manufacturing precision

If conventional methods requiring separate preparation of lipid mixture and RNAi solution are used, then the lipoplex can be produced with controlled formulation, but extensive labor is required at hospital prescription departments

Engineering Contradiction:
Improveformulation controlVSAvoidhospital preparation ease
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent merges the separately prepared lipid mixture and RNAi solution into a single integrated aqueous surfactant-based formulation. This combination maintains precise formulation control through standardized excipient concentrations while eliminating the need for separate preparation steps at hospital prescription departments

Inventive Principle:
Principle #5Merging (Combining)

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

This method enables efficient production of lipoplex powders that can be easily reconstituted for topical administration, effectively delivering RNAi molecules to tumor cells, thereby inhibiting tumor growth without the need for hazardous solvent handling or extensive labor in hospital settings.

Implementation Method 1

dissolving dioleylphosphatidylethanolamine (DOPE), phosphatidylcholine, and a cationic lipid in highly biotolerant and non-explosive ethanol

Methodology Applied
Scientific EffectDissolution: Solvation

Implementation Method 2

lyophilizing the solution and removing ethanol therefrom

Methodology Applied
Scientific EffectLyophilization: Freeze Drying

Data Source

PatentEP3213755B1New production method of lipoplex for local administration and antitumor drug using lipoplex
Publication Date: 2020.06.24 DELTA FLY PHARMA
  • EP3213755B1 patent drawingFigure 1
  • EP3213755B1 patent drawingFigure 2
  • EP3213755B1 patent drawingFigure 3

AI summary

An object of this invention is to provide a novel delivery means that enables efficient delivery of an active ingredient to a target cell. Such objective is attained by a lipoplex comprising dioleylphosphatidylethanolamine (DOPE), phosphatidylcholine, a cationic lipid, and an RNAi molecule and an industrial method for producing the same.