Cyclo(-His-Pro) Hydrate Polymorph for Stable Kidney Disease Formulation

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Solution Overview

Problem

Existing anhydrous forms of Cyclo(-His-Pro) are unstable due to physical and chemical instability, leading to the formation of diastereomers and are not suitable for stable therapeutic applications.

Innovation Solution

Development of a stable Cyclo(-His-Pro) hydrate form (Pattern 2) characterized by superior stability, achieved through crystallization using solvents, which can be used alone or in pharmaceutical compositions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If anhydrous form of cyclo (-His-Pro) is used, then it can be synthesized by conventional chemical methods, but it exhibits physical instability at ambient to high humidity conditions and chemical instability leading to diastereomer formation

Engineering Contradiction:

Improvesynthesis by conventional chemical methodsVSAvoidstability

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent applies parameter changes by converting the anhydrous form to a hydrate form, specifically incorporating water molecules into the crystal lattice structure. This changes the physical and chemical parameters of the compound, transforming it from an unstable anhydrous state to a stable hydrate state that resists degradation and diastereomer formation while maintaining synthesizability through conventional methods

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite material system where water molecules are integrated into the crystal lattice of cyclo (-His-Pro) to form a hydrate complex. This composite structure combines the active pharmaceutical ingredient with water in a specific stoichiometric ratio, creating a new material phase that exhibits enhanced stability properties while retaining the therapeutic activity of the original compound

Inventive Principle:

Principle #40Composite materials

2Adaptability or versatility

If Pattern 1 (anhydrous CHP) is used, then it has potential therapeutic applications, but it shows apparent physical instability and potential chemical instability due to water activity

Engineering Contradiction:

Improvetherapeutic applicationsVSAvoidphysical and chemical stability

Core Design Contradiction:

Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent converts the harmful effect of water activity, which causes chemical instability and diastereomer formation in the anhydrous form, into a beneficial feature by deliberately incorporating water into the crystal structure. The hydrate form transforms water from a destabilizing factor into a stabilizing component, where the structured water molecules in the lattice actually protect the compound from degradation and unwanted chemical transformations

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

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 Cyclo(-His-Pro) hydrate form exhibits enhanced stability, maintaining purity and form over extended periods, suitable for various pharmaceutical formulations and therapeutic applications.

Implementation Method 1

a process for isolating Pattern 2 by crystallization using solvents

Methodology Applied

Scientific EffectCrystallization: Crystallisation

Data Source

PatentUS12534496B2Polymorphic forms of Cyclo (-His-Pro) and methods of use to treat kidney disease

Publication Date: 2026.01.27 NOVMETAPHARMA CO LTD

AI summary

The present disclosure relates to synthesis and characterization of novel polymorphic forms of Cyclo (-His-Pro) (“CHP”).