一种烟酰胺单核苷酸的结晶方法

Crystallization method of nicotinamide mononucleotide

文档序号：2572 发布日期：2021-09-17 浏览：61次中文

1. A method for crystallizing nicotinamide mononucleotide,

the method comprises the following steps: concentrating nicotinamide mononucleotide aqueous solution to a concentration of 10-1000g/L, adding anhydrous ethanol for overnight, fully crystallizing, carrying out solid-liquid separation to obtain wet crystals, and drying to obtain the nicotinamide mononucleotide.

2. The method of crystallizing nicotinamide mononucleotide according to claim 1, wherein said crystallization step comprises the step of,

also comprises adding crystal habit modifier before adding anhydrous alcohol overnight.

3. The method of crystallizing nicotinamide mononucleotide according to claim 2, wherein said crystallization step comprises,

the addition amount of the crystal habit modifier is 5-40g corresponding to 1L of nicotinamide mononucleotide aqueous solution.

4. The method of crystallizing nicotinamide mononucleotide according to claim 1, wherein said crystallization step comprises the step of,

corresponding to 1L of nicotinamide mononucleotide in water, the amount of the absolute ethanol added is 1500-2400 g.

5. A method of crystallizing nicotinamide mononucleotide according to any one of claims 1 to 4, characterized in that,

the crystallization time is 8-15h, preferably 9-12 h.

6. The method of crystallizing nicotinamide mononucleotide according to claim 5, characterized in that,

in the crystallization process, the temperature of the solution is controlled to be 5-35 ℃, and preferably 8-23 ℃.

7. A method of crystallizing nicotinamide mononucleotide according to any one of claims 1-6, characterized in that,

controlling the concentration of the concentrated nicotinamide mononucleotide aqueous solution to be 80-200 g/L.

8. A method of crystallizing nicotinamide mononucleotide according to any one of claims 1-7, characterized in that,

the solid-liquid separation is suction filtration;

and/or, the drying is vacuum drying, preferably at 40-65 ℃.

9. Nicotinamide mononucleotide crystallized by the crystallization method of any one of claims 1-8.

10. Nicotinamide mononucleotide according to claim 9, characterized in that,

the dry powder bulk density and the angle of repose of the nicotinamide mononucleotide are 0.25-0.65g/ml and 40-60 degrees respectively.

Background

Nicotinamide Mononucleotide (NMN) is an important substance, has a molecular weight of 334.2192, is one of substances inherent to a human body, and is also rich in some fruits and vegetables; NMN plays an important role in the generation of human body cell energy, is a synthetic intermediate of intracellular NAD (nicotinamide adenine dinucleotide, an important coenzyme for cell energy conversion), plays a key role in the energy metabolism of cells, and has great application value in the field of medicines.

Research shows that NMN acts on mouse to show antisenility effect, and NMN has obvious effect on preventing diabetes, Alzheimer's disease, heart failure and other diseases and improving symptoms. However, in the prior art, the nicotinamide mononucleotide product crystallized by the elution crystallization method has poor fluidity, low density and easy generation of static electricity, and cannot completely meet the requirements of practical application.

In view of this, how to further optimize the crystallization method of nicotinamide mononucleotide based on the prior art, improve the crystallization efficiency, improve the quality of nicotinamide mononucleotide, and reduce the cost thereof is a key technical problem to be solved by those skilled in the art.

Disclosure of Invention

Aiming at the technical problems in the prior art, the invention provides a crystallization method of nicotinamide mononucleotide.

The invention adopts the following technical scheme:

a method of crystallizing nicotinamide mononucleotide comprising:

concentrating nicotinamide mononucleotide aqueous solution to a concentration of 10-1000g/L, adding anhydrous ethanol for overnight, fully crystallizing, carrying out solid-liquid separation to obtain wet crystals, and drying to obtain the nicotinamide mononucleotide.

In the above technical solution, the crystallization method of nicotinamide mononucleotide further comprises:

before adding anhydrous ethanol overnight, adding crystal habit agent.

Further, in the above technical scheme, the addition amount of the crystal habit modifier is 5-40g corresponding to 1L of nicotinamide mononucleotide aqueous solution.

In the above technical scheme, the addition amount of the anhydrous ethanol is 1500-2400g corresponding to 1L of the aqueous solution of nicotinamide mononucleotide.

Still further, in the above technical solution, in the crystallization process of nicotinamide mononucleotide, the crystallization time is 8-15h, preferably 9-12 h.

In a preferred embodiment of the present invention, the temperature of the solution is controlled to be 5-35 deg.C, preferably 8-23 deg.C, during the crystallization of nicotinamide mononucleotide.

Still further, in the above technical means, in the crystallization of nicotinamide mononucleotide, the concentration of concentrated aqueous solution of nicotinamide mononucleotide is controlled to be 80-200 g/L.

Specifically, in the above technical scheme, in the crystallization process of nicotinamide mononucleotide, the solid-liquid separation is suction filtration.

Specifically, in the above technical scheme, in the crystallization process of nicotinamide mononucleotide, the drying is vacuum drying, preferably vacuum drying at 40-65 ℃.

The invention also provides nicotinamide mononucleotide crystallized by the crystallization method.

Specifically, the dry powder bulk density and angle of repose of nicotinamide mononucleotide crystallized by adopting the crystallization method are 0.25-0.65g/ml and 40-60 degrees respectively.

Compared with the prior art, the invention has the beneficial effects that:

the invention provides a concentration-fed-batch alcohol-liquid two-step crystallization method of nicotinamide mononucleotide, and a crystallization habit modifier is added before the dissolution crystallization, so that the obtained nicotinamide mononucleotide has good fluidity, large particle density, difficult generation of static electricity, easy packaging and good practical application prospect.

Detailed Description

The present invention is further described in detail below with reference to specific examples so that those skilled in the art can more clearly understand the present invention.

The following examples are provided only for illustrating the present invention and are not intended to limit the scope of the present invention.

All other embodiments obtained by a person skilled in the art based on the specific embodiments of the present invention without any inventive step are within the scope of the present invention.

In the embodiments of the present invention, all components are commercially available products well known to those skilled in the art unless otherwise specified.

In the examples of the present invention, unless otherwise specified, all technical means used are conventional means well known to those skilled in the art.

In the examples of the present invention, the method for preparing nicotinamide mononucleotide used is as follows:

1. raw materials

2. Process for the preparation of a coating

Adding ribose-1-cyclohexylammonium phosphate salt, nicotinamide, adenosine triphosphate and magnesium chloride hexahydrate into triethanolamine buffer solution, uniformly mixing, adjusting the pH and the temperature of the buffer solution to be 8 and 55 ℃, adding PNPII enzyme and NRK enzyme, carrying out heat preservation and stirring for enzymatic reaction until ribose-1-cyclohexylammonium phosphate salt is completely consumed, adsorbing by HZ-818 type macroporous resin, and crystallizing to obtain nicotinamide mononucleotide.

Example 1