Injectable Collagen Suspensions for Dense Matrix Formation

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Solution Overview

Problem

Current methods for preparing collagen-based tissue substitutes often result in matrices that are not very concentrated, denatured, crosslinked, or contaminated with organic solvents and chemical reagents, posing toxicity and stability issues.

Innovation Solution

Development of injectable collagen suspensions comprising undenatured, non-crosslinked, and non-denatured collagen particles with a high concentration, free from contaminants, which can form dense, stable matrices upon injection, using a process involving acid-soluble collagen solutions and controlled drying techniques.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If acid-soluble collagen is aerosol-dried at high temperatures (120°C) to obtain concentrated particles, then collagen concentration is improved, but the collagen triple helices are denatured

Engineering Contradiction:
Improvecollagen concentrationVSAvoidcollagen triple helix structure
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the drying temperature parameter from conventional high temperatures (120°C) to low temperatures (below 40°C, preferably 20-30°C). This parameter change allows the collagen particles to be dried without denaturing the triple helix structure, while still achieving concentrated particles suitable for injection.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses a disposable syringe with a fine needle for the injection process, eliminating the need for complex, reusable injection devices. The syringe is designed for single-use, which simplifies the system and reduces contamination risks while delivering the collagen suspension effectively.

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

2Quantity of substance

If organic solvents (ethanol, acetone, diethyl ether) are used to precipitate collagen particles, then collagen concentration is improved, but toxicity problems arise during injection

Engineering Contradiction:
Improvecollagen concentrationVSAvoidtoxicity
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes the harmful organic solvents from the collagen preparation process. Instead of using organic solvents for precipitation, the invention employs an aqueous buffer system (phosphate-buffered saline) to achieve collagen particle formation, thereby eliminating toxicity while maintaining concentration.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces an aqueous buffer system (phosphate-buffered saline) as an intermediary medium to replace organic solvents. This intermediary allows for collagen particle precipitation and stabilization without the toxic effects of organic compounds, making the formulation safe for injection.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If collagen is injected at high concentration to form dense matrices, then matrix density is improved, but injectability becomes difficult

Engineering Contradiction:
Improvecollagen concentrationVSAvoidinjectability
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The patent segments the collagen into microparticles (0.1-10 μm) rather than using bulk collagen. This segmentation allows the material to be injected through fine needles (27-30 gauge) while maintaining high concentration, as the particles can pass through the needle lumen without causing excessive resistance or tissue damage.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes the particle size parameter to within the range of 0.1-10 μm, which optimizes both injectability and matrix density. This parameter adjustment allows the collagen suspension to flow through fine needles while forming dense matrices upon injection, resolving the contradiction between concentration and ease of injection.

Inventive Principle:
Principle #35Parameter changes

4Stability of the object's composition

If collagen matrices are formed without crosslinking to maintain native structure, then collagen integrity is improved, but stability against collagenases deteriorates

Engineering Contradiction:
Improvecollagen triple helix integrityVSAvoidresistance to collagenases
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The patent applies preliminary physical stabilization through controlled cooling and buffering during the injection process. The low-temperature drying and aqueous buffer formulation create a physically stable particle structure that resists enzymatic degradation without requiring chemical crosslinking, thereby maintaining integrity while improving stability.

Inventive Principle:
Principle #10Preliminary action

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 resulting collagen suspensions can be easily injected through fine needles, form stable dense matrices, and are resistant to collagenases, maintaining the integrity of collagen triple helices, thus providing a safe and effective tissue substitute.

Implementation Method 1

The invention relates to an injectable suspension consisting of a pulverulent composition consisting of solid spherical or spheroid particles consisting of more than 90% by mass of undenatured and non-crosslinked collagen

Methodology Applied
Scientific EffectAtomization:

Implementation Method 2

using a process involving acid-soluble collagen solutions and controlled drying techniques

Methodology Applied
Scientific EffectControlled drying: Evaporation

Implementation Method 3

the resulting collagen suspensions can be easily injected through fine needles, form stable dense matrices

Methodology Applied
Scientific EffectAggregation: Coagulation

Data Source

PatentEP3270882B1Injectable collagen suspensions, the preparation method thereof, and the uses thereof, particularly for forming dense collagen matrices
Publication Date: 2023.06.07 CENT NAT DE LA RECH SCI (C N R S)
  • EP3270882B1 patent drawingFigure 1~2
  • EP3270882B1 patent drawingFigure 3~4
  • EP3270882B1 patent drawingFigure 5~6

AI summary

The present invention relates to the preparation of injectable collagen suspensions, to the method for preparing said suspensions, and to the uses thereof, particularly for forming dense collagen matrices.