Liposome Production Apparatus Temperature Control

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Solution Overview

Problem

Conventional methods for producing liposomes face challenges in achieving uniform diameters, leading to low utility value and increased manufacturing costs due to non-uniform particle-size distribution and reduced yield.

Innovation Solution

A liposome-producing apparatus and method involving heating a mixture of lipids, water, and a water-miscible organic solvent to a temperature between 62° C. to 80° C., maintaining it at 40° C. or higher for a predetermined period, and then cooling it to form liposomes with uniform diameters.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If water is added to a solution of lipid in t-butanol while maintaining the temperature, then the lipid solution is diluted and t-butanol is diluted, but the amount of lipid dissolved decreases resulting in lipid separation and non-uniform reaction progression

Engineering Contradiction:
Improveease of liposome productionVSAvoiduniformity of liposome diameter
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by controlling temperature as a critical parameter during the liposome formation process. Specifically, the mixture is heated to 62-80°C to dissolve lipids, then cooled to 40°C or higher but lower than the heating temperature to form liposomes. This temperature parameter control ensures uniform lipid dissolution and prevents lipid separation during water addition, thereby achieving uniform liposome diameters while maintaining ease of production

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies preliminary action by pre-dissolving lipids in the aqueous solution containing water-miscible organic solvent at elevated temperature (62-80°C) before adding water. This preliminary dissolution step ensures complete lipid solubility and uniform distribution before the actual liposome formation process begins, preventing lipid separation and ensuring uniform reaction progression throughout the process

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If an appropriate pore size filter is used to narrow the particle-size distribution, then the particle-size distribution can be narrowed, but the yield of liposomes with specific desired particle-size distribution is reduced

Engineering Contradiction:
Improveuniformity of liposome diameterVSAvoidyield of liposomes
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent applies parameter changes by optimizing the temperature parameters during liposome formation to directly control particle-size distribution. By maintaining the temperature at 40°C or higher but lower than the heating temperature during the formation process, the patent achieves uniform liposome diameters without requiring post-formation filtration, thereby maintaining high yield while achieving the desired particle-size uniformity

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If the area to be sterilized is extended to subject liposomes to filtration process, then the particle-size distribution can be controlled, but the manufacturing cost increases

Engineering Contradiction:
Improveparticle-size distribution controlVSAvoidmanufacturing cost
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent applies parameter changes by controlling temperature during the liposome formation process to inherently achieve uniform particle-size distribution, eliminating the need for extended sterilization filtration processes. This approach reduces the manufacturing area requiring sterilization and thereby lowers manufacturing costs while maintaining precise particle-size control

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 approach allows for the easy production of liposomes with uniform diameters, improving their utility value and reducing manufacturing costs by maintaining consistent lipid concentration and reaction conditions.

Implementation Method 1

heating a mixture containing one or more lipids, water, and a water-miscible organic solvent to a temperature in a range of 62° C. to 80° C.

Methodology Applied
Scientific EffectHeating: Heating

Implementation Method 2

a first cooling zone being located in the downstream side of the dissolving zone in the solution sending direction for cooling the solution from the dissolving zone to a temperature that is lower than the temperature of the dissolving zone and that allows formation of liposomes

Methodology Applied
Scientific EffectCooling: Cooling

Data Source

PatentUS8951450B2Apparatus and method for production of liposomes
Publication Date: 2015.02.10 TORAY ENG CO LTD
  • US8951450B2 patent drawing
  • US8951450B2 patent drawing
  • US8951450B2 patent drawing

AI summary

Disclosed are: an apparatus which enables the easy production of liposomes having uniform particle diameters; and others. Specifically disclosed is a liposome production apparatus comprising: a microtube having a flow path through which a lipid-dissolved solution comprising at least one lipid, water and a water-miscible organic solvent can pass; a housing section in which the microtube is accommodated; and a cooling means for cooling the dissolved solution contained in the microtube in the housing section to a temperature at which liposomes can be produced. The apparatus enables the production of liposomes having uniform particle diameters.