Tryptophan Derivative Crystalline Solvate Salt for Stability

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Pharmaceutical compositions containing amino acid derivatives, such as tryptophan derivatives, face challenges with stability, solubility, and bioavailability, particularly in aqueous solutions, which limits their effectiveness and suitability for pharmaceutical applications due to issues like cyclization and poor crystalline forms.

Innovation Solution

A crystalline solvate salt compound formed with C3-C4 alkyl alcohols, specifically sodium or potassium salts, which enhances purity, solubility, and stability, allowing for effective pharmaceutical compositions suitable for various administration routes, including ocular, oral, and nasal administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Shape

If conventional salt forms (hydrochloride, sulfate, phosphate, etc.) are used, then crystalline structure is achieved, but solubility and stability deteriorate due to amorphous or glassy physical state

Engineering Contradiction:

Improvecrystalline structureVSAvoidstability

Core Design Contradiction:

ShapeVSStability of the object's composition

Solution Approach 1:

The patent changes the counterion parameter from conventional choices (chloride, sulfate, phosphate) to hydroxide, and introduces solvent molecules (ethanol, isopropanol, acetone) into the crystal lattice as solvates. This parameter change results in a crystalline structure that is both stable and highly soluble, overcoming the trade-off between crystallinity and solubility/stability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates composite crystalline structures where the tryptophan derivative, counterion (hydroxide), and solvent molecules coexist in a defined stoichiometric ratio within the crystal lattice. This composite approach allows the material to exhibit both crystalline stability and enhanced solubility through the integrated solvent components

Inventive Principle:

Principle #40Composite materials

2Shape

If hydrochloride salt form is used, then crystalline structure can be obtained, but purity and stability worsen due to waxy or glassy brownish solid formation and non-stoichiometric composition

Engineering Contradiction:

Improvecrystalline structureVSAvoidpurity

Core Design Contradiction:

ShapeVSManufacturing precision

Solution Approach 1:

The patent changes the counterion from chloride to hydroxide, which fundamentally alters the crystal packing and stoichiometry. This parameter change eliminates the waxy/glassy morphology and non-stoichiometric composition issues, yielding a pure crystalline hydroxide salt with defined solvent incorporation

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

Solvent molecules (ethanol, isopropanol, acetone) act as intermediaries in the crystal lattice, mediating between the tryptophan derivative and hydroxide counterion. This intermediary role of the solvent enables stable crystalline formation with improved purity and stoichiometry

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If amino acid derivatives are formulated as aqueous solutions, then bioavailability is improved, but stability deteriorates due to cyclization to diketopiperazine

Engineering Contradiction:

ImprovebioavailabilityVSAvoidstability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the molecular form from free amino acid derivative to crystalline hydroxide salt solvate. This parameter change in chemical state (from neutral to ionic) and physical state (from amorphous to crystalline) simultaneously improves both stability (preventing cyclization) and bioavailability (through enhanced solubility)

Inventive Principle:

Principle #35Parameter changes

4Ease of manufacture

If compound (1) is used in conventional salt forms, then pharmaceutical formulation is achieved, but solubility deteriorates to very low levels in water and organic solvents

Engineering Contradiction:

Improvepharmaceutical formulationVSAvoidsolubility

Core Design Contradiction:

Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent changes the salt form parameter to hydroxide and incorporates solvent molecules in defined ratios, creating a crystalline structure with dramatically enhanced solubility properties while maintaining pharmaceutical formulation compatibility

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite material where solvent molecules are integrated into the crystal lattice structure, resulting in a material that combines the stability of crystalline form with the solubility benefits of solvent incorporation, achieving both manufacturability and high solubility

Inventive Principle:

Principle #40Composite materials

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 crystalline solvate salt form achieves high purity (>99.7%) and increased water solubility, addressing stability concerns and improving bioavailability, making it suitable for treating amyloid-associated diseases with enhanced therapeutic efficacy.

Implementation Method 1

crystalline structure of a solvate salt compound (1), wherein said solvate is a C 3 -C 4 alkyl alcohol thereof

Methodology Applied

Scientific EffectSolvation: Solvation

Data Source

PatentEP4157266B1Crystalline forms of solvates of tryptophan derivatives, compositions comprising them and uses thereof

Publication Date: 2024.07.03 GALIMEDIX THERAPEUTICS INC

AI summary

The invention provides crystalline forms of solvates of tryptophan derivatives of compound (1), compositions comprising them, processes for their preparations and methods of use thereof.