A method for crystallizing d-chiro-inositol

Abstract

The application discloses a crystallization method of D-chiro-inositol, and relates to the technical field of inositol crystallization. A D-chiro-inositol feed liquid is sequentially subjected to cation exchange resin, anion exchange resin and macroporous decoloring resin, a decoloring liquid obtained through the above steps is concentrated to 15-20 Baume through a nanofiltration membrane, then concentrated to 28-34 Baume under the conditions of a temperature of 70-90 DEG C and a vacuum of <-0.09 MPa, the temperature of the concentrated liquid is maintained at 50-60 DEG C, ethanol is added dropwise into the concentrated liquid while stirring, the obtained mixed liquid is subjected to staged temperature reduction, suction filtration, ethanol washing and vacuum drying to obtain D-chiro-inositol products, and the obtained D-chiro-inositol crystal is in a uniform crystal form, has a particle size of 20-40 mesh, and the content of the D-chiro-inositol crystal is greater than 86%, the D-chiro-inositol crystal is good in uniformity, easy to filter and capable of realizing industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of inositol crystallization, in particular to a crystallization method of D-chiro inositol. BACKGROUND

[0002] D-chiro inositol (DCI) is a white powder, easily soluble in water, slightly soluble in organic solvents such as ethanol and methanol, and is one of the nine isomers of inositol with optical activity. It is also a bioactive isomer of vitamin B8, and exists in buckwheat seeds, soybeans and some insects at a relatively high level, mostly in the form of methylated or glycosylated derivatives, and is the biodegradation product of buckwheat sugar alcohol. It has insulin-sensitizing effect and promotes liver fat metabolism function, and can significantly reduce blood sugar content, and has significant therapeutic effect on diabetes. In addition, DCI also has the effects of improving polycystic ovarian syndrome (PCOS), antioxidant, anti-aging, free radical scavenging, etc., and has good utilization value.

[0003] In recent years, with the development of production engineering technology, biotransformation synthesis of D-chiro inositol has become a new development trend. At present, it is mainly researched from two aspects of transforming inositol into chiral inositol by modifying microorganisms and improving the conversion rate. However, there are few studies on the crystallization of subsequent chiral inositol. Chinese patent CN104961628A discloses a method for converting D-pinitol into D-chiro inositol. The method uses D-pinitol, which widely exists in nature, as raw material, and uses acid hydrolysis method to demethylate D-pinitol to convert it into D-chiro inositol, and then removes the acid from the acid solution. Compared with other methods of using chemical synthesis of D-chiro inositol, this method has the advantages of safety, high efficiency and less pollution. Under the optimized experimental conditions, the purity of D-chiro inositol is 94.2%, the purity is low, the temperature of room temperature crystallization is low, the obtained crystal is small, the crystal mesh distribution is not concentrated, and the crystallization time is long, which increases the crystallization period. SUMMARY

[0004] The technical problem to be solved by the present application is to provide a crystallization method of D-chiro inositol, which has the advantages of short crystallization period, high purity of product and good uniformity of crystal mesh.

[0005] To solve the above technical problems, the technical scheme of the present application is as follows:

[0006] A crystallization method of D-chiro inositol, comprising the following steps:

[0007] A: The D-chiro inositol solution is first subjected to cation exchange resin and then subjected to anion exchange resin to obtain a desalted solution;

[0008] B: The desalted solution is decolorized by passing through a macroporous decolorizing resin to obtain a decolorized solution;

[0009] C: The decolorized solution is concentrated to 15-20 Baume by nanofiltration membrane to obtain a nanofiltration concentrated solution;

[0010] D: The nanofiltration concentrated solution is concentrated to 28-34 Baume under the conditions of temperature 70-90℃ and vacuum <-0.09MPa to obtain a concentrated solution;

[0011] E: The concentrated solution is maintained at temperature 50-60℃, and ethanol is added dropwise to the concentrated solution while stirring to obtain a mixed solution;

[0012] F: The mixed solution is cooled to 40-45℃ at a stirring speed of 150-180rpm at a rate of 1-2℃ / h, then cooled to 30-35℃ at a stirring speed of 120-150rpm at a rate of 2-4℃ / h, then cooled to 20-25℃ at a stirring speed of 80-120rpm at a rate of 4-7℃ / h, and finally cooled to 5-10℃ at a stirring speed of 50-80rpm at a rate of 7-10℃ / h, and then filtered, washed with ethanol, and dried under vacuum to obtain the D-chiro-inositol product.

[0013] Preferably, the flow rate of the cation exchange resin and the anion exchange resin in step A is 1-3BV / h.

[0014] Preferably, the mass content of the D-chiro-inositol feed solution in step A is 5-10wt%.

[0015] Preferably, the flow rate of the desalted solution through the macroporous decolorizing resin in step B is 2-6BV / h.

[0016] Preferably, the nanofiltration membrane in step C has an inlet pressure of 2.5-3.5MPa, an outlet pressure of 2.0-3.0MPa, and a pore size of 100-300nm.

[0017] Preferably, the ratio of the volume of ethanol to the volume of the concentrated solution in step E is 0.5-1.0:1.

[0018] Preferably, the dropwise addition of ethanol in step E takes 0.5-1h.

[0019] Preferably, the stirring speed during the dropwise addition in step E is 150-200rpm.

[0020] Preferably, the drying temperature in step F is 40-60℃, and the vacuum degree is <-0.09MPa.

[0021] Preferably, the purity of the D-chiro-inositol product in step F is >99.6%, and the particle size of the product is >86% between 20-40mesh.

[0022] With the above technical scheme, the application has the following beneficial effects:

[0023] 1. The application has simple process and easy operation, can effectively reduce production running cost, greatly shorten production cycle, and lay a foundation for realizing large-scale industrial production.

[0024] 2. The application obtains large-granular D-chiro-inositol crystal with uniform crystal form, granularity of 20-40 meshes, and >86% by using the method of segmental cooling crystallization, cooperating with different stirring speed and cooling rate, good uniformity, easy to filter, and can realize industrial production.

[0025] 3. The nanofiltration membrane in the application can concentrate the decolorized liquid, save energy consumption of subsequent concentration, remove part of small molecular impurities and salt ions in the feed liquid, and make the purity of D-chiro-inositol product >99.6%, and the product quality is high. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 is a crystallization graph of D-chiro-inositol product in example 1 of the application under 10 times optical microscope;

[0027] Figure 2 is a liquid phase detection graph of D-chiro-inositol product in example 1 of the application. DETAILED DESCRIPTION

[0028] The application will be further described in combination with examples.

[0029] Example 1

[0030] 10L of D-chiro-inositol feed liquid with a concentration of 5%wt is first passed through cation exchange resin (D001) at a flow rate of 1BV / h, and then passed through anion exchange resin (D201) at a flow rate of 1BV / h, to obtain 11L of desalted liquid. The desalted liquid is decolorized by macroporous decolorizing resin (LS109) at a flow rate of 2BV / h, to obtain 12L of decolorized liquid. The decolorized liquid is concentrated by nanofiltration membrane with a pore size of 100nm, the inlet membrane pressure is controlled at 2.5MPa, the outlet membrane pressure is controlled at 2.0MPa, 3.4L of 15 Baume nanofiltration concentrated liquid is obtained. The nanofiltration concentrated liquid is concentrated to 28 Baume under the condition of a temperature of 70℃ and a vacuum of <-0.09MPa, the volume is 1.82L. 0.91L of 95% ethanol is added dropwise into the concentrated liquid, the dropwise adding time is 0.5h. During the dropwise adding process of ethanol, the system temperature is controlled at 50℃, and the stirring speed is controlled at 150rpm.

[0031] The system was cooled to 40°C at a stirring speed of 150 rpm and a rate of 1°C / h, then cooled to 30°C at a stirring speed of 120 rpm and a rate of 2°C / h, then cooled to 20°C at a stirring speed of 80 rpm and a rate of 4°C / h, and finally cooled to 5°C at a stirring speed of 50 rpm and a rate of 7°C / h. The product was filtered, washed with 95% ethanol, and dried at 40°C under vacuum of <-0.09 MPa to obtain 461 g of D-chiro-inositol with a calculated crystallization yield of 92.2%, a crystal size of 86% between 20-40 meshes, and a purity of 99.6% detected by a liquid chromatograph.

[0032] Example 2

[0033] The D-chiro-inositol solution with a concentration of 8% wt was first passed through a cation exchange resin (D001) at a flow rate of 2 BV / h, and then passed through an anion exchange resin (D201) at a flow rate of 2 BV / h to obtain 11 L of a desalted solution. The desalted solution was decolorized by a macroporous decolorizing resin (LS109) at a flow rate of 4 BV / h to obtain 12 L of a decolorized solution. The decolorized solution was concentrated by a nanofiltration membrane with a pore size of 200 nm, with an inlet pressure of 3.0 MPa and an outlet pressure of 2.5 MPa, to obtain 4.5 L of a nanofiltration concentrated solution with an osmolarity of 18. The nanofiltration concentrated solution was concentrated to an osmolarity of 31 with a volume of 2.58 L at a temperature of 80°C under vacuum of <-0.09 MPa. Then, 2 L of 95% ethanol was added dropwise to the concentrated solution at a dropwise adding time of 0.8 h. During the dropwise adding of ethanol, the temperature of the system was controlled at 55°C and the stirring speed was 180 rpm.

[0034] The system was cooled to 43°C at a stirring speed of 180 rpm and a rate of 1.5°C / h, then cooled to 32°C at a stirring speed of 135 rpm and a rate of 3°C / h, then cooled to 23°C at a stirring speed of 100 rpm and a rate of 5°C / h, and finally cooled to 8°C at a stirring speed of 65 rpm and a rate of 8°C / h. The product was filtered, washed with 95% ethanol, and dried at 50°C under vacuum of <-0.09 MPa to obtain 752 g of D-chiro-inositol with a crystallization yield of 94.0%, a crystal size of 91% between 20-40 meshes, and a purity of 99.8% detected by a liquid chromatograph.

[0035] Example 3

[0036] Take 10% wt D-chiro-inositol solution 10L, first through cation exchange resin (D001), flow rate 3BV / h, then through anion exchange resin (D201), flow rate 3BV / h, to get desalted solution 11.5L, the desalted solution through macroporous decolorizing resin (LS109) decolorization, flow rate 6BV / h, to get decolorized solution 13L, the decolorized solution through 300nm nanofiltration membrane concentration, control the membrane pressure 3.5MPa, membrane pressure 3.0MPa, to get 20Bome nanofiltration concentrated solution 5.1L, nanofiltration concentrated solution in the temperature 90℃, vacuum <-0.09MPa conditions concentrated to 34Bome, volume 2.95L, to the concentrated solution drop 95% ethanol 2.95L, drop time 1h, drop ethanol process, control the system temperature 60℃, stirring speed 200rpm;

[0037] The system in stirring speed 200rpm, 2℃ / h rate cooling to 45℃, then in stirring speed 150rpm, 4℃ / h rate cooling to 35℃, then in stirring speed 120rpm, 7℃ / h rate cooling to 25℃, finally in stirring speed 80rpm, 10℃ / h rate cooling to 10℃, suction filtration, 95% ethanol washing, in 60℃, vacuum <-0.09MPa conditions drying to get D-chiro-inositol 932g, the calculated crystallization yield 93.4%, crystal size 90% between 20-40 mesh, through liquid chromatograph detection purity 99.6%.

[0038] It should be understood that the embodiments are only used to illustrate but not to limit the scope of the present application. Furthermore, it should be understood that after reading the content taught by the present application, those skilled in the art can make various alterations or modifications to the present application, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Claims

1. A crystallization method for D-chiro-inositol, characterized in that The following steps are involved: A: D-chiro-inositol feed solution is first passed through a cation exchange resin and then through an anion exchange resin to obtain a desalted solution, wherein the mass content of the D-chiro-inositol feed solution is 5-10%wt; B: The desalted liquid is decolorized by passing through a macroporous decolorizing resin to obtain a decolorized liquid; C: The decolorized liquid is concentrated to 15-20 Baume by nanofiltration membrane to obtain nanofiltration concentrate; D: The nanofiltration concentrate is concentrated to 28-34 baume at a temperature of 70-90°C and a vacuum of less than -0.09 MPa to obtain a concentrate; E: Maintain the concentrated solution temperature at 50-60°C and add ethanol dropwise to the concentrated solution while stirring to obtain a mixed solution; F: The mixed solution is cooled to 40-45°C at a rate of 1-2°C / h at a stirring speed of 150-180 rpm, then cooled to 30-35°C at a rate of 2-4°C / h at a stirring speed of 120-150 rpm, then cooled to 20-25°C at a rate of 4-7°C / h at a stirring speed of 80-120 rpm, and finally cooled to 5-10°C at a rate of 7-10°C / h at a stirring speed of 50-80 rpm. The mixture is filtered, washed with ethanol, and vacuum dried to obtain the finished D-chiro-inositol with a purity of >99.6% and a particle size of >86% between 20 and 40 mesh.

2. A method for crystallizing D-chiro-inositol according to claim 1, wherein: In step A, the column flow rates of the cation exchange resin and the anion exchange resin are both 1 to 3 BV / h.

3. A method for crystallizing D-chiro-inositol according to claim 1, wherein: In step B, the flow rate of the desalted liquid through the macroporous decolorizing resin is 2 to 6 BV / h.

4. A method for crystallizing D-chiro-inositol according to claim 1, wherein: In step C, the inlet pressure of the nanofiltration membrane is 2.5-3.5 MPa, the outlet pressure is 2.0-3.0 MPa, and the pore size of the nanofiltration membrane is 100-300 nm.

5. A method for crystallizing D-chiro-inositol as claimed in claim 1, wherein: In step E, the ratio of the added volume of ethanol to the volume of the concentrated solution is 0.5 to 1.0:

1.

6. A method for crystallizing D-chiro-inositol as claimed in claim 1, characterized in that: The dropwise addition time of ethanol in step E is 0.5 to 1 h.

7. A method for crystallizing D-chiro-inositol as claimed in claim 1, characterized in that: The stirring speed during the dropwise addition in step E is 150-200 rpm.

8. A method for crystallizing D-chiro-inositol as claimed in claim 1, characterized in that: In step F, the drying temperature is 40-60° C. and the vacuum degree is less than -0.09 MPa.

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