Peptide Composition for Cartilage Formation via COX-2 Activation

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Solution Overview

Problem

Current treatments for bone defects and osteoarthritis lack effective methods for promoting bone and cartilage regeneration, with existing therapies primarily focusing on pain management and temporary repair, while there is a need for therapies that can stimulate specific bone growth without ectopic ossification and promote cartilage repair.

Innovation Solution

A peptide compound with a specific amino acid sequence motif, such as DLXXXNDXXPFXXXXQXF, is used in combination with a pharmaceutically acceptable carrier for controlled release, stimulating growth of hard tissues like bone and cartilage, and activating COX-2 for cartilage formation, as demonstrated in goat models.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If BMP molecules are used to stimulate new bone formation, then bone formation activity is improved, but ectopic ossification occurs in soft tissues

Engineering Contradiction:
Improvebone formation activityVSAvoidectopic ossification
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and utilizes only the N-terminal fragment (residues 1-50) of the BMP-2 molecule, which contains the essential bone-forming activity while removing the C-terminal region responsible for non-selective bone formation and ectopic ossification. This fragmented approach preserves therapeutic benefit while eliminating harmful side effects.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The BMP-2(1-50) fragment exhibits localized and selective bone formation activity specifically at the implant site when combined with a biodegradable carrier, rather than causing widespread ectopic ossification. The carrier material confines the biological activity to the intended location, providing spatial control over the therapeutic effect.

Inventive Principle:
Principle #3Local quality

2Productivity

If BMP molecules are administered systemically, then bone formation is stimulated, but selectivity to bone tissue is lost

Engineering Contradiction:
Improvebone formation stimulationVSAvoidtissue selectivity
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

A biodegradable carrier material serves as an intermediary between the BMP-2(1-50) fragment and the target bone tissue. The carrier provides controlled local delivery, ensuring the peptide reaches and acts specifically on bone tissue at the implant site while preventing systemic distribution and maintaining high tissue selectivity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If carrier material is used for localized BMP delivery, then ectopic ossification is prevented, but device complexity increases

Engineering Contradiction:
Improveectopic ossification preventionVSAvoidcarrier material requirement
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The invention changes the molecular parameters of the BMP molecule by using a truncated fragment (1-50 residues) instead of the full-length protein. This parameter change allows the peptide to maintain bone-forming activity while requiring simpler carrier materials, as the smaller fragment has reduced potential for off-target effects and can be delivered through less complex delivery systems.

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 peptide compound effectively promotes cartilage and bone formation, showing dose-dependent regeneration in osteoarthritis models, potentially offering a more sustainable repair solution beyond current pain management approaches.

Implementation Method 1

AC-100 has also shown bone formation activities in vivo... demonstrated to stimulate proliferation, differentiation, and mineralization of human osteoblastic cells

Methodology Applied
Scientific EffectCell proliferation:

Implementation Method 2

stimulate proliferation, differentiation, and mineralization of human osteoblastic cells

Methodology Applied
Scientific EffectCell differentiation:

Implementation Method 3

stimulate proliferation, differentiation, and mineralization of human osteoblastic cells

Methodology Applied
Scientific EffectMineralization:

Implementation Method 4

activating COX-2 for cartilage formation

Methodology Applied
Scientific EffectEnzyme activation: Enzyme

Implementation Method 5

promote cartilage repair... effectively promotes cartilage and bone formation, showing dose-dependent regeneration in osteoarthritis models

Methodology Applied
Scientific EffectCartilage regeneration:

Implementation Method 6

A peptide compound with a specific amino acid sequence motif, such as DLXXXNDXXPFXXXXQXF, is used in combination with a pharmaceutically acceptable carrier for controlled release

Methodology Applied
Scientific EffectControlled release:

Data Source

PatentEP2117578B1A peptide composition and a method of promoting cartilage formation
Publication Date: 2015.04.22 ORTHOTROPHIX INC
  • EP2117578B1 patent drawingFigure 1
  • EP2117578B1 patent drawingFigure 2
  • EP2117578B1 patent drawingFigure 3

AI summary

The present invention is a peptide compound which stimulates the formation of hard tissues such as bone and cartilage. The invention is also related to a method to treat a defect in hard tissues such as bone and cartilage using the peptide. The method of the present invention may be used to treat or prevent the defects in bones and cartilages which are caused by rheumatoid arthritis or osteoarthritis which involves the regeneration of new bone or cartilage in or around the defects.