NMNH Disodium Monohydrate Crystal Form for Stable Storage
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Solution Overview
Problem
Current methods for producing reduced nicotinamide mononucleotide disodium monohydrate (NMNH) result in amorphous solids with poor stability, moisture absorption, and degradation, making them unsuitable for long-term storage and transportation.
Innovation Solution
Development of a crystalline form I of NMNH with specific X-ray powder diffraction peaks and improved thermal stability, achieved through controlled crystallization using ammonia water, thiourea dioxide, and sodium hydroxide, followed by purification and seeding.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If freeze-drying aqueous solutions is used to obtain NMNH products, then the production process is simple, but the products are amorphous solids with poor stability, moisture absorption, and degradation
Solution Approach 1:
The patent changes the physical state parameters of NMNH from amorphous to crystalline form through controlled crystallization process. By adjusting temperature, solvent composition, and crystallization conditions, the patent transforms the unstable amorphous freeze-dried solids into stable crystalline structures with defined X-ray diffraction patterns, thereby improving product stability while maintaining manufacturability
Solution Approach 2:
The patent utilizes phase transition from amorphous solid to crystalline solid through controlled crystallization. The process involves dissolving NMNH in water, adjusting pH and temperature, and allowing controlled crystallization to occur, transforming the material from an amorphous state (prone to degradation) to a crystalline state (stable and suitable for storage)
2Adaptability or versatility
If crystalline forms A, B, and C with variable water content are used, then the production flexibility is improved, but the storage stability deteriorates due to adsorbed water
Solution Approach 1:
The patent precisely controls the water content parameter by specifying 'monohydrate' form with fixed stoichiometric water molecules in the crystal structure. This is achieved through controlled crystallization conditions that ensure consistent formation of the monohydrate phase, eliminating the variable water content problem of prior art while maintaining production flexibility
Solution Approach 2:
The patent creates a well-defined composite crystalline structure where NMNH molecules are systematically combined with a specific amount of water (monohydrate) in a fixed stoichiometric ratio. This structured composite approach, verified by X-ray diffraction and thermogravimetric analysis, ensures consistent composition and improved storage stability compared to variable water content forms
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 form I exhibits enhanced hygroscopic resistance and stability, facilitating convenient storage and transportation, and is suitable for large-scale production with reduced production costs.
Implementation Method 1
which exhibits X-ray powder diffraction peaks at 2θ angles of 10.502°±0.2°, 12.721°±0.2°, 20.036°±0.2°, and 21.633°±0.2° using CuKα radiation
Implementation Method 2
achieved through controlled crystallization using ammonia water, thiourea dioxide, and sodium hydroxide, followed by purification and seeding
Data Source
AI summary
The invention relates to a crystalline form I of the reduced nicotinamide mononucleotide disodium monohydrate (NMNH) as shown in formula I, and its preparation method. The crystalline form I exhibits X-ray powder diffraction peaks at 2θ angles of 10.502°±0.2°, 12.721°±0.2°, 20.036°±0.2°, and 21.633°±0.2° using CuKα radiation. This crystalline form I has advantages such as good stability, low hygroscopicity, ease of storage, and a simple preparation method, making it suitable for large-scale production.