Amorphous Calcium Carbonate Stabilization via Phosphorylated Peptides

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Solution Overview

Problem

Current methods fail to effectively stabilize amorphous calcium carbonate (ACC) for use in pharmaceutical and nutraceutical compositions, as it tends to crystallize into less soluble forms, limiting its bioavailability and stability.

Innovation Solution

Incorporating phosphorylated amino acids or peptides, such as those from crustacean proteins like GAP65, GAP22, and GAP12, which inhibit the crystallization of calcium carbonate, maintaining the amorphous form and enhancing stability when combined with ACC in compositions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If amorphous calcium carbonate is used in compositions, then bioavailability and solubility are improved, but stability deteriorates as it transforms to crystalline polymorphs

Engineering Contradiction:
ImprovestabilityVSAvoidamorphous form stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

Phosphorylated peptides act as intermediary substances that mediate between the amorphous calcium carbonate and its tendency to crystallize. These peptides bind to the ACC surface and prevent direct transformation to crystalline forms, serving as a stabilizing intermediary layer that maintains the desired amorphous state while allowing controlled calcium release.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the chemical parameters of the system by introducing phosphorylated amino acid residues (phospho-serine or phospho-threonine) that alter the surface chemistry and thermodynamic properties of ACC. This parameter change prevents the spontaneous crystallization pathway while maintaining solubility and bioavailability characteristics.

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If crystalline polymorphs of calcium carbonate are formed, then stability is improved, but solubility and bioavailability worsen

Engineering Contradiction:
Improvecrystalline stabilityVSAvoidbioavailability
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

Instead of accepting the natural transformation from amorphous to crystalline form (which improves stability but reduces bioavailability), the invention inverts this process by using phosphorylated peptides to maintain the amorphous state. This inversion allows simultaneous achievement of both high stability and high bioavailability, reversing the conventional trade-off.

Inventive Principle:
Principle #13The other way round (Inversion)

3Stability of the object's composition

If phosphorylated peptides are added to stabilize ACC, then amorphous form stability is improved, but composition complexity worsens

Engineering Contradiction:
Improveamorphous form stabilityVSAvoidcomposition complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The phosphorylated peptides function as disposable stabilizing agents that perform their stabilizing role and can be metabolized or excreted. They are not permanent structural components but temporary functional additives that achieve stabilization without requiring complex long-term structural integration, thus limiting the increase in overall composition complexity.

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

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 use of phosphorylated peptides stabilizes ACC, maintaining its amorphous form for extended periods, improving bioavailability and stability, making it suitable for dietary supplements and therapeutic applications.

Implementation Method 1

Said phosphorylated amino acids and phosphorylated peptides stabilize the amorphous form of said calcium carbonate in the composition of the invention

Methodology Applied
Scientific EffectCrystallization inhibition: Crystallisation

Data Source

PatentUS10328100B2Stable amorphous calcium carbonate comprising synthetic phosphorylated peptides
Publication Date: 2019.06.25 AMORPHICAL LTD
  • US10328100B2 patent drawing
  • US10328100B2 patent drawing
  • US10328100B2 patent drawing

AI summary

Provided are compositions containing amorphous calcium carbonate (ACC), and at least one phosphorylated peptide which stabilizes the amorphous form of said calcium carbonate. Particularly, the peptide can be selected from crustacean proteins, also provided by the invention, namely GAP65, GAP22, GAP21, and GAP12 (also indicated herein as GAP10). The compositions are useful in pharmaceutical and nutraceutical formulations.