Ginsenoside C-K Crystal Forms D and H Stability

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Solution Overview

Problem

The existing crystal form of ginsenoside C-K, designated as crystal form G, has limitations in stability and bioavailability, affecting its therapeutic applications due to variations in physicochemical properties such as stability, flowability, and compressibility.

Innovation Solution

Two novel crystal forms, D and H of ginsenoside C-K, are developed, characterized by specific XRPD patterns and cell parameters, with methods involving solvent systems and preparation processes that include dissolution, filtration, and drying to enhance stability, including the formation of a monohydrate for crystal form D and use of specific solvents for crystal form H.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If crystal form G is used, then the existing crystal structure is available, but the stability and bioavailability are limited

Engineering Contradiction:

ImprovestabilityVSAvoidbioavailability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by modifying the crystal structure parameters of ginsenoside C-K through controlled crystallization processes. Different solvent systems (acetonitrile-water, ethanol-water, isopropanol-water) and temperature conditions are used to obtain crystal forms D and H with improved stability and bioavailability compared to crystal form G. The crystallization parameters including solvent composition, temperature, and pH are systematically adjusted to achieve the desired crystal properties.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If different crystal forms are developed, then stability and bioavailability improve, but the complexity of characterization and preparation increases

Engineering Contradiction:

ImprovestabilityVSAvoidcharacterization complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the characterization process into distinct analytical components: XRPD for crystal structure identification, DSC for thermal properties, and 13C NMR for molecular configuration verification. Each crystal form (D and H) is characterized by its specific diffraction pattern with distinctive peak positions, allowing clear differentiation and identification. This segmented approach systematically manages the complexity of characterizing multiple crystal forms.

Inventive Principle:

Principle #1Segmentation

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 new crystal forms demonstrate improved stability and bioavailability, maintaining their structure under elevated temperatures, outperforming the existing crystal form G in thermostability and potentially enhancing the therapeutic efficacy of ginsenoside C-K.

Implementation Method 1

there are diffraction peaks at 2θ values (°) of about 6.39, 12.71, 13.30, 15.79, 16.14, 16.44, 20.03, 20.74 and 24.29 in the XRPD pattern

Methodology Applied

Scientific EffectX-ray diffraction: X-Ray

Implementation Method 2

diffraction peaks at 2θ values (°) of about 6.39, 12.71, 13.30, 15.79, 16.14, 16.44, 20.03, 20.74 and 24.29 in the XRPD pattern

Methodology Applied

Scientific EffectBragg diffraction: Bragg Diffraction

Implementation Method 3

The crystal form D of ginsenoside C-K has an endothermic peak at around 154±5° C. in the DSC pattern

Methodology Applied

Scientific EffectEndothermic reaction: Endothermic Reaction

Data Source

PatentUS9643992B2Two crystal forms of ginsenoside C-K and method for preparing same

Publication Date: 2017.05.09 ZHEJIANG HISUN PHARMA CO LTD

AI summary

Provided are ginsenoside C-K polymorphic forms and a method for preparing same. The ginsenoside C-K polymorphic forms are crystal form D and crystal form H.