3',5'-cyclic diguanylic acid free acid crystallization

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Conventional methods for obtaining 3',5'-cyclic diguanylic acid crystals are unsuitable for large-scale production in a short time and raise safety concerns due to the inclusion of metal salts, while methods for free acid crystals are unknown, limiting their pharmaceutical applications.

Innovation Solution

A method involving the addition of acid to an aqueous solution of 3',5'-cyclic diguanylic acid to lower the pH to 1 to 3, allowing for the crystallization of free acid crystals without metal salts, which are stable and easy to handle.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If the vapor diffusion method is used to obtain 3’,5’-cyclic diguanylic acid crystals, then the crystals can be obtained with good quality, but the production efficiency is low and large amount of crystals cannot be obtained in a short period of time

Engineering Contradiction:
Improvecrystal qualityVSAvoidproduction efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The invention changes the crystallization parameters from vapor diffusion to acidification method. By lowering the pH to 1-3 through acid addition, the invention achieves rapid crystallization while maintaining crystal quality, thereby resolving the contradiction between manufacturing precision and productivity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention utilizes phase transition of 3’,5’-cyclic diguanylic acid from dissolved state to crystalline state through pH-induced precipitation. This phase transition approach enables rapid crystal formation compared to the slow vapor diffusion process, improving productivity while maintaining crystal quality

Inventive Principle:
Principle #36Phase transitions

2Ease of manufacture

If co-crystals with metal salts (cobalt or magnesium) are used, then the crystals can be obtained easily, but safety problems arise when intended for pharmaceutical raw material applications

Engineering Contradiction:
Improvecrystal obtainabilityVSAvoidsafety concerns
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and eliminates the harmful metal salt components from the crystal structure. By using acidification to precipitate free acid crystals instead of co-crystals, the invention removes cobalt and magnesium salts while maintaining crystal formation, thereby resolving the safety concerns for pharmaceutical applications

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the use of expensive and potentially harmful metal salts with simple acid additives. This substitution uses inexpensive acids (hydrochloric acid, sulfuric acid, or nitric acid) to achieve crystal precipitation without introducing harmful metal ions, resolving the safety issue while maintaining ease of manufacture

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 method enables the production of stable, metal-ion-free 3',5'-cyclic diguanylic acid crystals with high purity and stability, suitable for pharmaceutical applications, and characterized by specific diffraction angles and thermal properties.

Implementation Method 1

adding acid to an aqueous solution of 3’,5’-cyclic diguanylic acid so as to lower pH to 1 to 3

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Implementation Method 2

preparation is possible by adding acid to an aqueous solution of 3’,5’-cyclic diguanylic acid so as to lower pH to 1 to 3

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Data Source

PatentEP3121188B1Crystalline 3',5'-cyclic diguanylic acid
Publication Date: 2021.12.29 YAMASA SHOYU CO LTD
  • EP3121188B1 patent drawingFigure 1~2
  • EP3121188B1 patent drawingFigure 3~4
  • EP3121188B1 patent drawingFigure 5~6

AI summary

A crystal of free acid of 3',5'-cyclic diguanylic acid containing no metal salt with cobalt, magnesium or the like is provided. A method is sought for obtaining said crystal in a large amount and with ease. By a manufacturing method comprising a step of adding acid to an aqueous solution of 3',5'-cyclic diguanylic acid so as to lower pH to 1 to 3, crystals of 3',5'-cyclic diguanylic acid can be obtained in a large amount with ease. Said crystals are free acid crystals which do not contain a metal salt with cobalt, magnesium or the like.