Nanoparticle Preparation via Wet Grinding and Anti-coagulation

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Solution Overview

Problem

Conventional methods for preparing nanoparticles face limitations in achieving sizes smaller than micrometers, and often result in particle growth or coagulation during water removal steps, especially when using excessive sodium chloride or organic solvents, which complicates the production of uniform nanoparticles with low water solubility active ingredients.

Innovation Solution

A method involving the uniform mixing of a saccharide as an anti-coagulation agent, biocompatible polymer, and/or surfactant with an active ingredient in the presence of water, followed by drying and grinding using a roll mill to produce nanoparticles with a controlled water content of 0.1 to 15 wt.%, facilitating efficient nanoparticle formation without excessive sodium chloride or organic solvents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Length of moving object

If conventional mechanical processes (crushing, grinding, milling) are used to reduce particle size, then particle size is reduced, but the minimum particle size is limited to about tens of micrometers and cannot achieve nanoscale

Engineering Contradiction:
Improveparticle sizeVSAvoidminimum particle size limitation
Core Design Contradiction:
Length of moving objectVSManufacturing precision

Solution Approach 1:

The invention changes the fundamental parameter of the grinding process by introducing a liquid medium (water or alcohol) to enable wet grinding, transforming the process from dry mechanical grinding to liquid-assisted grinding. This parameter change allows particles to be reduced to nanoscale (0.1-10 µm) by preventing particle aggregation through liquid separation, thereby overcoming the micrometer limitation of conventional dry grinding processes

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention introduces liquid medium (water or alcohol) as an intermediary substance between the grinding media and particles. This intermediary prevents direct particle-to-particle contact and aggregation during grinding, enabling sustained reduction to nanoscale sizes. The liquid medium acts as a separator that maintains particle dispersion while allowing mechanical energy to be applied for size reduction

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If excessive sodium chloride is used as anti-coagulation agent, then particle re-coagulation is prevented, but additional steps for removing sodium chloride are required

Engineering Contradiction:
Improveparticle stabilityVSAvoidprocess complexity
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The invention extracts and eliminates sodium chloride from the formulation by using alternative anti-coagulation agents (carboxymethyl cellulose sodium, hydroxypropyl cellulose, or polyethylene glycol) that are biocompatible and do not require removal steps. This extraction of the problematic substance simplifies the manufacturing process while maintaining particle stability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces permanent sodium chloride additives with biodegradable polymers (carboxymethyl cellulose sodium, hydroxypropyl cellulose) that serve their anti-coagulation function and then naturally degrade, eliminating the need for removal steps. These disposable-like functional agents provide temporary protection during processing and then disappear, simplifying the overall process

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Length of moving object

If wet grinding process is used to produce nanoparticles, then nanoscale particles are achieved, but particle growth or coagulation occurs during water removal steps

Engineering Contradiction:
Improveparticle sizeVSAvoidparticle uniformity
Core Design Contradiction:
Length of moving objectVSStability of the object's composition

Solution Approach 1:

The invention applies preliminary action by adding carboxymethyl cellulose sodium or other anti-coagulation agents to the wet grinding mixture before the water removal step. This preliminary protection ensures particles remain dispersed and prevented from aggregating during subsequent drying. The anti-coagulation agent is pre-positioned to protect particles during the vulnerable water removal phase, maintaining nanoscale uniformity

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention provides beforehand cushioning by incorporating biocompatible polymers (carboxymethyl cellulose sodium, hydroxypropyl cellulose, or polyethylene glycol) that create a protective barrier around particles before water removal. This cushioning effect prevents particle-particle contact and aggregation during drying, preserving the nanoscale size distribution achieved during wet grinding

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

4Ease of manufacture

If dry grinding is used to produce nanoparticles, then processing is simplified, but particles cannot be reduced below micrometer size

Engineering Contradiction:
Improveprocess simplicityVSAvoidparticle size
Core Design Contradiction:
Ease of manufactureVSLength of moving object

Solution Approach 1:

The invention changes the physical state parameter of the grinding environment from dry to wet, introducing liquid medium to enable nanoscale particle formation. This parameter change fundamentally alters the grinding mechanics, allowing particles to be reduced to 0.1-10 µm by preventing aggregation through liquid separation, thereby achieving nanoscale sizes that are impossible with conventional dry grinding processes

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

This method effectively produces nanoparticles with sizes of 5µm or less, overcoming the limitations of traditional dry grinding and avoiding particle growth, and can be applied to active ingredients with low water solubility, ensuring high uniformity and stability of the final nanoparticle powder.

Implementation Method 1

uniformly mixing saccharide as an anti-coagulation agent

Methodology Applied
Scientific EffectAnti-coagulation: Coagulation

Implementation Method 2

drying the mixture to obtain a dried mixture

Methodology Applied
Scientific EffectDrying: Desiccation

Implementation Method 3

grinding the dried mixture with a roll mill

Methodology Applied
Scientific EffectMechanical grinding: Abrasion

Implementation Method 4

biocompatible polymer and/or surfactant

Methodology Applied
Scientific EffectSurfactant action: Surfactant

Data Source

PatentEP2551237B1Method for preparing nano-particles
Publication Date: 2024.09.04 BIO SYNECTICS
  • EP2551237B1 patent drawingFigure 1~2
  • EP2551237B1 patent drawingFigure 3~4
  • EP2551237B1 patent drawingFigure 5~6

AI summary

The present invention relates to a method for preparing nano-particles, and more particularly, to a method for preparing nano-particles containing active materials in a simple and highly efficient manner through a grinding process.