Preparation method of D-chiro-inositol

Abstract

The invention discloses a preparation method of D-chiro-inositol, and relates to the technical field of D-chiro-inositol production, and the preparation method comprises the following steps: filtering a D-chiro-inositol conversion liquid through diatomite and an ultrafiltration membrane, carrying out cation exchange resin and anion exchange resin, then carrying out vacuum concentration on the effluent through a nanofiltration membrane until crystals are separated out, and then carrying out cooling crystallization to obtain the D-chiro-inositol. Collecting a filter cake I and a filtrate I, concentrating the filtrate I under vacuum until the solid content is 50-60% w / w, then adding ethanol, heating and filtering, collecting a filter cake II and a filtrate II, cooling the filtrate II to 10-15 DEG C, filtering and collecting a filter cake III and a filtrate III, adding pure water into the filter cake III for dissolving to obtain a dissolving solution, adding water which is 0.5-1 time of the weight of the filter cake and dissolving at 50-80 DEG C, cooling and crystallizing the dissolving solution, and filtering to obtain the product. Cooling to 10-15 DEG C, filtering and collecting a filter cake IV and a filtrate IV, and drying the filter cake IV to obtain the D-chiro-inositol, the process is simple, the cost is low, and the yield is high.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of D-chiro inositol production, and particularly relates to a preparation method of D-chiro inositol. BACKGROUND

[0002] D-chiro inositol (DCI) is one of nine isomers of inositol with optical activity, is a bioactive isomer of vitamin B8, exists in buckwheat seeds, soybeans and some insects at a relatively high level, and exists in the form of methylation or glycosylation derivatives, is a biodegradation product of buckwheat sugar alcohol, has insulin-sensitizing effect and promotes liver fat metabolism function, 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 and the like, and has good utilization value.

[0003] D-chiro inositol can be extracted from plants such as buckwheat, but the content of D-chiro inositol in these plants is not high, resulting in poor utilization rate of resources and high cost of separation and extraction. D-chiro inositol can also be prepared by organic synthesis method, but due to complicated steps, it is difficult to separate by-products, and toxic substances are left, which affects the quality of the product; in addition, a large amount of organic solvents are used, and the environmental friendliness is poor. In addition, D-chiro inositol can be produced by hydrolyzing D-pinitol or spring day mycosin, but the price of raw material D-pinitol or spring day mycosin is expensive, so the economy is poor.

[0004] In recent years, bioconversion synthesis of D-chiro inositol has become a new development trend, and at present, research is mainly carried out from two aspects of converting myo-inositol into chiro inositol by modifying microorganisms and improving conversion rate, but the conversion rate is low, and D-chiro inositol and myo-inositol obtained are difficult to separate, resulting in low purity of D-chiro inositol, and it is difficult to realize industrialized production, therefore, it is urgent to develop a preparation method of D-chiro inositol with simple production process, low cost and high yield. SUMMARY

[0005] The technical problem to be solved by the present application is to provide a preparation method of D-chiro inositol in view of the deficiencies in the prior art, which has simple process, low cost and high yield.

[0006] To solve the above technical problems, the technical scheme of the present application is as follows:

[0007] A preparation method of D-chiro inositol, comprising the following steps:

[0008] A: Take a D-chiro-inositol conversion solution containing 12-15% D-chiro-inositol and 85-88% myo-inositol, add 3-5% diatomaceous earth by volume of the conversion solution, heat to 80-90°C, keep warm for 10-30 minutes, filter, and collect the filtrate;

[0009] B: The filtrate is filtered through an ultrafiltration membrane and the ultrafiltration clear liquid is collected;

[0010] C: The ultrafiltration clear fluid is first passed through a cation exchange resin and then an anion exchange resin, and the effluent is collected. The cation exchange resin is SQD-61 and the anion exchange resin is LS-4539;

[0011] D: The effluent is concentrated through a nanofiltration membrane to a solid content of 12-15% w / w to obtain a nanofiltration concentrate;

[0012] E: The nanofiltration concentrate is concentrated under vacuum <-0.09 MPa and a temperature of 70-90°C until crystals precipitate, then cooled to 15-20°C for crystallization, filtered, and the filter cake I and filtrate I are collected;

[0013] F: Filtrate I is concentrated under vacuum <-0.09 MPa and a temperature of 70-90°C to a solid content of 50-60% w / w, followed by addition of ethanol, heating to 60-70°C, and filtering to collect filter cake II and filtrate II;

[0014] G: Cool the filtrate II to 10-15°C, and collect the filter cake III and filtrate III by filtration;

[0015] H: Add pure water to the filter cake III to dissolve it to obtain a solution. The amount of water added is 0.5-1 times the weight of the filter cake. The dissolution temperature is 50-80℃;

[0016] I: The dissolved solution is cooled to 10-15°C for crystallization, and the filter cake IV and filtrate IV are collected by filtration. The filter cake IV is dried to obtain D-chiro-inositol.

[0017] Preferably, the molecular weight cut-off of the ultrafiltration membrane in step B is 2500-5000 Da.

[0018] Preferably, the feed flow rate of the cation exchange resin and the anion exchange resin in step C is 1-2 BV / h;

[0019] Before use, the cation exchange resin is regenerated with a 4-5% wt hydrochloric acid solution, and the anion exchange resin is regenerated with a 4-5% wt sodium hydroxide solution.

[0020] Preferably, the molecular weight cut-off of the nanofiltration membrane in step D is 200-250 Da, and the membrane inlet pressure of the nanofiltration membrane is 3-3.5 MPa.

[0021] Preferably, the filter cake I in step E is myo-inositol, which is recovered and reconverted.

[0022] Preferably, the amount of ethanol added in step F is 0.8-1.5 times the volume of the concentrated solution, and the filter cake II is myo-inositol and a small amount of D-chiro-inositol, which are recovered and re-converted.

[0023] Preferably, the filtrate III in step G is distilled to recover ethanol.

[0024] Preferably, 1-3% by volume of activated carbon is added to the solution in step I for decolorization for 20-40 minutes, filtered, the decolorized solution is collected, and then the decolorized solution is cooled and crystallized.

[0025] Preferably, the solution in step I is cooled to 10-15°C at a rate of 5-10°C / h.

[0026] Preferably, the filtrate IV in step I is applied to the filtrate I and then concentrated.

[0027] Due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0028] 1. Use diatomaceous earth adsorption combined with ultrafiltration membrane to quickly remove large molecular impurities (such as proteins and colloids), reduce subsequent resin contamination, and shorten process time.

[0029] 2. The cation resin and anion resin are regenerated with hydrochloric acid and sodium hydroxide respectively to remove charged impurities (such as inorganic salts and organic acids) in a targeted manner, avoiding the complex operation of traditional multi-stage purification.

[0030] 3. Through differential solubility (myo-inositol has low solubility in ethanol) and staged concentration crystallization (filtrate I → filter cake III), efficient separation of D-chiro-inositol and myo-inositol is achieved, avoiding the tedious operation of repeated recrystallization.

[0031] 4. Nanofiltration membrane pre-concentration at 3-3.5MPa significantly reduces the energy consumption of subsequent vacuum concentration, and ethanol recovery (filtrate III distillation) reduces solvent costs.

[0032] 5. Filter cakes I and II (containing myo-inositol) can be re-entered into the conversion process to improve raw material utilization. Filtrate IV can be applied to filtrate I to reduce the loss of D-chiro-inositol.

[0033] 6. Nanofiltration concentration is controlled at 12-15% solid content to avoid over-concentration leading to co-crystallization and ensure that myo-inositol is preferentially precipitated (filter cake I). After filtrate I is concentrated to 50-60% w / w solid content, ethanol is added to selectively precipitate myo-inositol (filter cake II), retaining D-chiro-inositol in filtrate II and increasing the yield by 10-15%.

[0034] 7. The D-chiro-inositol precipitates with purity >99% after cooling the filtrate II, and the mother liquor (filtrate IV) is reused to further reduce the loss, so that the total yield can reach more than 85% (about 70% in the traditional process). BRIEF DESCRIPTION OF DRAWINGS

[0035] Figure 1 is a chromatogram of D-chiro-inositol in Example 1 of the present application;

[0036] Figure 2 is a crystal graph of D-chiro-inositol in Example 1 of the present application under 10 times optical microscope. DETAILED DESCRIPTION

[0037] The present application is further described below in conjunction with examples.

[0038] Example 1

[0039] 1. Take 50 L of D-chiro-inositol conversion solution, wherein the D-chiro-inositol accounts for 12% in the conversion solution, and myo-inositol accounts for 88%;

[0040] 2. Add 3% of the volume of diatomite to the conversion solution, heat to 80°C, and keep for 10 min, then filter to collect 49 L of filtrate, and the filter cake is treated in an environmentally friendly manner;

[0041] 3. Filter the filtrate through an ultrafiltration membrane, and collect 50 L of ultrafiltration clear solution, wherein the ultrafiltration membrane is selected to be 2500 Da;

[0042] 4. First pass the ultrafiltration clear solution through a cation exchange resin at a feed flow rate of 1 BV / h, and then pass it through an anion exchange resin at a feed flow rate of 1 BV / h, and collect 61 L of effluent, wherein the cation exchange resin is selected to be SQD-61, the anion exchange resin is selected to be LS-4539, the cation exchange resin is regenerated with 4% wt concentration of hydrochloric acid before use, and the anion exchange resin is regenerated with 4% wt concentration of sodium hydroxide;

[0043] 5. Concentrate the column effluent through a nanofiltration membrane to a solid content of 12% w / w, collect 40 L of nanofiltration concentrated solution, and select the nanofiltration membrane to be 200 Da, and control the membrane inlet pressure to be 3 MPa;

[0044] 6. Concentrate the nanofiltration concentrated solution under the conditions of vacuum < -0.09 MPa and temperature 70°C, and after crystallization, reduce the temperature to 15°C, filter, and collect 2580 g of filter cake I and 11 L of filtrate I, wherein the filter cake I is myo-inositol, which can be recycled for re-conversion;

[0045] 7. Filtrate I was concentrated under vacuum conditions of <-0.09 MPa and a temperature of 70°C to a solid content of 50% w / w. Ethanol (0.8 times the volume of the concentrate) was then added, and the mixture was heated to 60°C and filtered. 1420 g of filter cake II and 6 L of filtrate II were collected. Filter cake II consisted of myo-inositol and a small amount of D-chiro-inositol, which could be recovered for further conversion.

[0046] 8. Filtrate II was cooled to 10°C, and 680 g of filter cake III and 5.5 L of filtrate III were collected by filtration. 2.5 L of ethanol was recovered from filtrate III by distillation, with a recovery rate of 98.2%.

[0047] 9. Dissolve filter cake III in pure water at a rate of 0.5 times the weight of the filter cake at a temperature of 50°C to obtain 0.9 L of solution.

[0048] 10. Add 1% by volume activated carbon to the solution for decolorization for 20 minutes, filter, and collect 0.9 L of decolorized solution;

[0049] 11. The decolorized solution was cooled and crystallized at a rate of 5°C / h to 10°C. Filter cake IV (530 g) and filtrate IV (0.52 L) were collected. D-chiro-inositol was obtained by drying filter cake IV with a yield of 88.3% and a purity of 99.6%. Filtrate IV was applied to filtrate I and concentrated.

[0050] Example 2

[0051] 1. Take 50L of D-chiro-inositol conversion solution, in which D-chiro-inositol accounts for 13% and myo-inositol accounts for 87%;

[0052] 2. Add 4% of the volume of the feed solution to diatomaceous earth into the conversion solution, raise the temperature to 85°C, keep warm for 20 minutes, filter, collect 50L of the filtrate, and dispose of the filter cake in an environmentally friendly manner;

[0053] 3. The filtrate was filtered through an ultrafiltration membrane, and 51 L of ultrafiltration supernatant was collected. The ultrafiltration membrane was selected to be 4000 Da;

[0054] 4. The ultrafiltrate was first passed through a cation exchange resin at a feed rate of 1.5 BV / h, and then passed through an anion exchange resin at a feed rate of 1.5 BV / h. 61 L of effluent was collected. The cation exchange resin was SQD-61 and the anion exchange resin was LS-4539. The cation exchange resin was regenerated with 5% wt hydrochloric acid before use, and the anion exchange resin was regenerated with 5% wt sodium hydroxide.

[0055] 5. The column liquid was concentrated through a nanofiltration membrane to a solid content of 13% w / w, and 38 L of nanofiltration concentrate was collected. The nanofiltration membrane was selected to be 250 Da, and the membrane inlet pressure was controlled at 3.2 MPa;

[0056] 6. The nanofiltration concentrate was concentrated under vacuum <-0.09 MPa and a temperature of 80°C until crystals precipitated, then cooled to 18°C ​​for crystallization, filtered, and 2635 g of filter cake I and 10.5 L of filtrate I were collected. Filter cake I was myo-inositol, which could be recovered for further conversion.

[0057] 7. Filtrate I was concentrated under vacuum conditions of <-0.09 MPa and a temperature of 80°C to a solid content of 55% w / w. Ethanol (one volume times the volume of the concentrate) was then added, and the mixture was heated to 65°C and filtered. 1450 g of filter cake II and 7 L of filtrate II were collected. Filter cake II consisted of myo-inositol and a small amount of D-chiro-inositol, which could be recovered for further conversion.

[0058] 8. Filtrate II was cooled to 12°C, and 650 g of filter cake III and 6.4 L of filtrate III were collected by filtration. 3.5 L of ethanol was recovered from filtrate III by distillation, with a recovery rate of 98.1%;

[0059] 9. Dissolve filter cake III in pure water at a rate of 0.8 times the weight of the filter cake at a temperature of 70°C to obtain 1.1 L of solution.

[0060] 10. Add 2% by volume activated carbon to the solution for decolorization for 30 minutes, filter, and collect 1.1 L of decolorized solution;

[0061] 11. The decolorized solution was cooled and crystallized at a rate of 7°C / h to 12°C. Filter cake IV (570 g) and filtrate IV (0.63 L) were collected. D-chiro-inositol was obtained by drying filter cake IV with a yield of 87.7% and a purity of 99.5%. Filtrate IV was applied to filtrate I and concentrated.

[0062] Example 3

[0063] 1. Take 50L of D-chiro-inositol conversion solution, in which D-chiro-inositol accounts for 15% and myo-inositol accounts for 85%;

[0064] 2. Add diatomaceous earth (5% of the volume of the feed solution) to the conversion solution, raise the temperature to 90°C, keep warm for 30 minutes, filter, collect 48L of filtrate, and dispose of the filter cake in an environmentally friendly manner;

[0065] 3. The filtrate was filtered through an ultrafiltration membrane and 50 L of ultrafiltration clear liquid was collected. The ultrafiltration membrane was selected to be 5000 Da.

[0066] 4. The ultrafiltrate was first passed through a cation exchange resin at a feed rate of 2 BV / h, and then passed through an anion exchange resin at a feed rate of 2 BV / h. 60 L of effluent was collected. The cation exchange resin was SQD-61 and the anion exchange resin was LS-4539. The cation exchange resin was regenerated with 5% wt hydrochloric acid before use, and the anion exchange resin was regenerated with 5% wt sodium hydroxide.

[0067] 5. The filtrate is concentrated by nanofiltration membrane, the concentration is 15% w / w, the nanofiltration concentrated solution is 33L, the nanofiltration membrane is 250Da, the pressure is 3.5MPa;

[0068] 6. The nanofiltration concentrated solution is concentrated under the condition of vacuum <-0.09Mpa and temperature 90℃, the concentration is until crystal is precipitated, then the temperature is decreased to 20℃, the filter cake I is 2600g and the filtrate I is 10.8L, the filter cake I is myo-inositol, which can be recycled for re-conversion;

[0069] 7. The filtrate I is concentrated under the condition of vacuum <-0.09Mpa and temperature 90℃, the concentration is 60% w / w, then 1.5 times volume of ethanol is added, the temperature is heated to 70℃, the filter cake II is 1550g and the filtrate II is 9L, the filter cake II is myo-inositol and a small amount of D-chiro-inositol, which can be recycled for re-conversion;

[0070] 8. The filtrate II is cooled to 15℃, the filter cake III is 750g and the filtrate III is 8.4L, the filtrate III is distilled to recover 4.5L of ethanol, the recovery rate is 98.0%;

[0071] 9. The filter cake III is dissolved in pure water, the amount of water is 1 times the weight of the filter cake, the temperature is 80℃, the dissolved solution is 1.3L;

[0072] 10. The dissolved solution is decolorized by adding 3% volume of activated carbon for 40min, the decolorized solution is 1.3L;

[0073] 11. The decolorized solution is cooled to crystallize, the temperature is decreased to 15℃ at the rate of 10℃ / h, the filter cake IV is 648g and the filtrate IV is 0.6L, the filter cake IV is dried to be D-chiro-inositol, the yield is 86.4%, the purity is 99.4%, and the filtrate IV is used for the filtrate I for re-concentration.

[0074] It should be understood that the embodiments are only used for illustrating the present application but not for limiting the scope of the present application. Furthermore, it should be understood that after reading the content of the present application, those skilled in the art can make various modifications or changes 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 method for preparing D-chiro-inositol, characterized in that The following steps are involved: A: Take a D-chiro-inositol conversion solution containing 12-15% D-chiro-inositol and 85-88% myo-inositol, add 3-5% diatomaceous earth by volume of the conversion solution, heat to 80-90°C, keep warm for 10-30 minutes, filter, and collect the filtrate; B: The filtrate is filtered through an ultrafiltration membrane and the ultrafiltration clear liquid is collected; C: The ultrafiltration clear fluid first passes through a cation exchange resin, then an anion exchange resin, and the effluent is collected; D: The effluent is concentrated through a nanofiltration membrane to a solid content of 12-15% w / w to obtain a nanofiltration concentrate; E: The nanofiltration concentrate is concentrated under vacuum <-0.09 MPa and a temperature of 70-90°C until crystals precipitate, then cooled to 15-20°C for crystallization, filtered, and the filter cake I and filtrate I are collected; F: Filtrate I is concentrated under vacuum <-0.09 MPa and a temperature of 70-90°C to a solid content of 50-60% w / w, followed by addition of ethanol, heating to 60-70°C, and filtering to collect filter cake II and filtrate II; G: Cool the filtrate II to 10-15°C, and collect the filter cake III and filtrate III by filtration; H: Add pure water to the filter cake III to dissolve it to obtain a solution. The amount of water added is 0.5-1 times the weight of the filter cake. The dissolution temperature is 50-80℃; I: The dissolved solution is cooled to 10-15°C for crystallization, and the filter cake IV and filtrate IV are collected by filtration. The filter cake IV is dried to obtain D-chiro-inositol.

2. A method for preparing D-chiro-inositol as claimed in claim 1, wherein: The molecular weight cut-off of the ultrafiltration membrane in step B is 2500-5000Da.

3. A method for preparing D-chiro-inositol as claimed in claim 1, wherein: In step C, the feed flow rate of the cation exchange resin and the anion exchange resin is 1-2 BV / h; Before use, the cation exchange resin is regenerated with a hydrochloric acid solution with a concentration of 4-5% wt, and the anion exchange resin is regenerated with a sodium hydroxide solution with a concentration of 4-5% wt.

4. A method for preparing D-chiro-inositol as claimed in claim 1, characterized in that: The molecular weight cut-off of the nanofiltration membrane in step D is 200-250 Da, and the membrane inlet pressure of the nanofiltration membrane is 3-3.5 MPa.

5. A method for preparing D-chiro-inositol as claimed in claim 1, characterized in that: The filter cake I in step E is myo-inositol, which is recovered and reconverted.

6. A method for preparing D-chiro-inositol as claimed in claim 1, characterized in that: In step F, the amount of ethanol added is 0.8-1.5 times the volume of the concentrated solution, and the filter cake II is myo-inositol and a small amount of D-chiro-inositol, which are recovered and re-converted.

7. A method for preparing D-chiro-inositol as claimed in claim 1, characterized in that: The filtrate III in step G is distilled to recover ethanol.

8. A method for preparing D-chiro-inositol as claimed in claim 1, characterized in that: Add 1-3% by volume of activated carbon to the solution in step I for decolorization for 20-40 minutes, filter, collect the decolorized solution, and then cool the decolorized solution for crystallization.

9. A method for preparing D-chiro-inositol as claimed in claim 1, characterized in that: The dissolved solution in step I is cooled to 10-15°C at a rate of 5-10°C / h.

10. The method for preparing D-chiro-inositol according to claim 1, wherein: The filtrate IV in step I is applied to the filtrate I and then concentrated.

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