Separation and preparation method of scyllo-inositol

Abstract

The invention discloses a separation and preparation method of scyllo-inositol, and relates to the technical field of scyllo-inositol production, a conversion liquid containing scyllo-inositol is heated and inactivated, the pH value is adjusted, the conversion liquid enters a ceramic membrane, an ultrafiltration membrane, a cation exchange resin column, a macroporous decolorizing resin column and an anion exchange resin column respectively, the obtained desalted liquid is concentrated until the solid content of the feed liquid is 20-30% w / w, and the concentrated liquid is dried to obtain the scyllo-inositol. And then cooling and adding pure scyllo-inositol as a seed crystal, cooling to 35-40 DEG C at the speed of 0.1-0.5 DEG C / h, and filtering to obtain a crude scyllo-inositol product. In the whole process, scyllo-inositol-boric acid composite salt is not formed, acidolysis of the composite salt is not needed subsequently, the process is shortened, meanwhile, the yield is increased, the production cost and the equipment cost are saved, boric acid residues do not exist in a finished product, the finished product is safer and easier to accept by consumers, the preparation process is safer, and the method is more friendly to personnel health and the ecological environment. Boron-containing mother liquor does not need to be treated, and the input amount of environment-friendly facilities is smaller.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of scyllitol production, and particularly relates to a separation and preparation method of scyllitol. BACKGROUND

[0002] Inositol is a cyclohexanol compound widely existing in organisms. One of its isomers, L-chiro-inositol, has shown important application value in the fields of medicine and health products in recent years.

[0003] At present, the industrial production of scyllitol mainly depends on extraction from plants or chemical conversion from myo-inositol which is cheap. However, whether by extraction or by conversion, the obtained product is a mixture of scyllitol and a large amount of other isomers such as myo-inositol. Because the physicochemical properties of scyllitol and myo-inositol are very similar, efficient and high-purity separation of scyllitol from the mixture has always been a major technical challenge in this field.

[0004] The traditional separation and purification process generally uses boric acid complexation. This method takes advantage of the fact that scyllitol can form stable complex crystals with boric acid, while myo-inositol has weaker complexing ability. Although this method has been applied for a certain period of time, its inherent serious defects have limited the development of the industry:

[0005] 1. Poor safety: Boric acid is a compound that is toxic and harmful to the human body, and has reproductive and developmental toxicity. The use of boric acid may cause the risk of boric acid residues in the final product, causing consumers to worry about the safety of the product, and it is difficult to meet the increasingly strict food and drug regulations.

[0006] 2. Complex process, high cost: The process is long and needs to go through complexation, acidolysis, and boron removal, which not only leads to long production cycle and high energy consumption, but also increases equipment investment and factory floor area. At the same time, the long process flow also causes loss of target product yield.

[0007] 3. Serious environmental pollution: A large amount of boric acid-containing waste acid mother liquor is generated during production, which is difficult to treat and needs expensive special environmental protection facilities for neutralization and degradation, otherwise it will cause persistent pollution to the environment, and the environmental protection pressure of enterprises is huge.

[0008] In addition, the traditional purification method (such as single activated carbon decolorization) has limited ability to remove pigments and small molecule impurities in the feed liquid that affect crystallization, resulting in low crystallization efficiency, low product purity, poor crystal morphology, and difficulty in meeting the needs of high-end markets.

[0009] Therefore, developing a green and safe, simple process, high yield and low cost of separation and preparation technology of scyllitol has become a problem to be solved for those skilled in the art. SUMMARY

[0010] The technical problem solved by the present application is to provide a separation and preparation method of scyllitol, which is simple in process, high in product yield, low in cost and friendly to the environment.

[0011] To solve the above technical problems, the technical scheme of the present application is:

[0012] A separation and preparation method of scyllitol, comprising the following steps:

[0013] A: The conversion solution containing scyllitol is inactivated by heating, then glacial acetic acid is added to adjust the pH to 3-5, ceramic membrane filtration is carried out, and the ceramic membrane clear liquid is collected;

[0014] B: The ceramic membrane clear liquid is subjected to ultrafiltration membrane filtration, and the ultrafiltration membrane clear liquid is collected;

[0015] C: The ultrafiltration membrane clear liquid is subjected to cation exchange resin column, the effluent is adjusted to pH 2-3, then subjected to macroporous decolorizing resin column, and the decolorizing liquid I is collected, then the decolorizing liquid I is subjected to anion exchange resin column to obtain a desalted liquid;

[0016] D: The desalted liquid is concentrated to a solid content of 20-30% w / w under the conditions of 50-70℃ and vacuum < -0.09MPa to obtain a concentrated liquid;

[0017] E: The concentrated liquid is cooled to 45℃, then scyllitol pure product is added as a crystal seed, then cooled to 35-40℃ at a speed of 0.1-0.5℃ / h, filtered, and the filter cake and the crude crystallization mother liquor are collected, and the filter cake is washed with pure water to obtain a scyllitol crude product.

[0018] Preferably, the inactivation temperature in step A is 70-90℃, and after inactivation, flocculation is carried out for 30min, then cooled to 30℃, glacial acetic acid is added to adjust the pH, then 50-100ppm of polyaspartic acid salt is added, and then ceramic membrane filtration is carried out.

[0019] Preferably, the filter pore size of the ceramic membrane is 20-50nm, and the molecular weight cut-off of the ultrafiltration membrane is 800-1000Da.

[0020] Preferably, the ultrafiltration membrane clear liquid in step C is subjected to nanofiltration membrane to obtain a nanofiltration membrane clear liquid, and the nanofiltration membrane has a molecular weight cut-off of 200-300Da.

[0021] The feeding speed of the cation exchange resin column, the macroporous decolorizing resin column and the anion exchange resin column is 1-2BV / h.

[0022] Preferably, the crude crystallization mother liquor in step E is recycled to the conversion solution containing scyllite to perform step A again.

[0023] The amount of scyllite pure product added as seed crystal is 0.1-0.5% w / v of the volume of the concentrated solution.

[0024] Preferably, the scyllite crude product is dissolved in pure water, activated carbon is added after complete dissolution for decolorization, and a ternary mixed solvent of ethanol-water-ethyl acetate or ethanol-water-acetone is added to the decolorized solution II obtained after filtration, and the crystal is grown and then crystallized by cooling, filtered to obtain a refined mother liquor and a filter cake, and the filter cake is dried to obtain the scyllite product.

[0025] Preferably, the scyllite crude product is dissolved in pure water at 70-80°C, the amount of dissolution is 3-5% w / v, the amount of activated carbon added is 2-5% w / w of the weight of the scyllite crude product, and the decolorization time is 20-40 min.

[0026] Preferably, the amount of the ternary mixed solvent added is 0.5-1 times the volume of the decolorized solution II, and the volume ratio of water, ethanol and ethyl acetate / acetone in the ternary mixed solvent is 60-70: 15-25: 15-25.

[0027] Preferably, the crystal growth temperature is 40-60°C, the crystal growth time is 0.5-1 h, and the temperature is lowered to 5-15°C after crystal growth.

[0028] Preferably, the refined mother liquor is recycled for the dissolution of the scyllite crude product.

[0029] Due to the adoption of the above technical solutions, the application has the following beneficial effects:

[0030] 1. The ice acetic acid adjusts the pH to make the protein denatured and flocculated, and then the coagulant aid polyaspartate is added to form larger and denser flocs through "bridging" effect, which greatly reduces the pollution load of the subsequent ceramic membrane, not only reducing the blockage, but also significantly improving the membrane flux and cleaning cycle, thereby improving the efficiency and reducing the long-term operation cost.

[0031] 2. The nanofiltration membrane can effectively remove part of the monovalent salt (such as NaCl) and almost all divalent salt in the feed solution, while retaining scyllite, which can significantly reduce the load of the subsequent ion exchange resin, prolong the service life of the resin, reduce the regeneration frequency and wastewater production.

[0032] 3. Gradient cooling and controlled addition of seed crystals can effectively inhibit burst nucleation, promote uniform and slow crystal growth, and form crystals with larger particles and more uniform particle size. Such crystals are less likely to wrap the mother liquor during filtration, and the elution effect is better, which improves the purity and yield of the crude product. At the same time, the slower cooling rate allows more time for scyllite to remain in the mother liquor, improving the separation efficiency.

[0033] 4. The ternary mixed solvent can more finely adjust the solubility and supersaturation of scyllitol, obtain more excellent crystal morphology and purity than single solvent, and make the product crystal more beautiful and higher in purity.

[0034] 5. The concentrated solution is rapidly cooled to near the saturation point (45℃), then cooled to the target temperature (35-40℃) at a very slow rate (0.1-0.5℃ / h). When near the saturation point, add finely ground scyllitol pure product as a crystal seed, filter, collect the filter cake, and rinse the filter cake with a small amount of pure water to remove the inositol solution remaining on the crystal, and the filter cake is the scyllitol crude product. The separation process is achieved by the difference in solubility of scyllitol and muscle inositol, so that the separation effect is achieved. At this temperature, the solubility of scyllitol is about 1%, and the solubility of muscle inositol is about 25%, so the solubility difference between the two components is large, thereby achieving the separation effect. The crude crystallization mother liquor can be returned to the previous conversion liquid storage tank, realizing the recycling of muscle inositol.

[0035] 6. The separation and preparation process of the present application does not use borate which is more harmful, shortens the preparation process, does not form scyllitol-borate complex salt in the intermediate process, and does not need to acidify the complex salt later, thereby shortening the process, increasing the yield, saving the production cost and equipment cost, and not having borate residue in the finished product, which is safer and more easily accepted by consumers, and is safer in the preparation process, more friendly to personnel health and ecological environment, does not need to handle boron-containing mother liquor, and needs less environmental protection facilities. BRIEF DESCRIPTION OF DRAWINGS

[0036] Figure 1 is the liquid chromatogram of the scyllitol product in Example 1 of the present application. DETAILED DESCRIPTION

[0037] The present application will be further described below in combination with examples.

[0038] Example 1

[0039] A separation and preparation method of scyllitol, comprising the following steps:

[0040] A: 50L of conversion liquid containing scyllitol (18g / L) is warmed to 70℃ for inactivation, cooled to 30℃ after flocculation for 30min, then pH is adjusted to 3 by adding glacial acetic acid, and 50ppm of polyaspartic acid salt is added, followed by filtration through a ceramic membrane with a pore size of 20nm, and 50L of ceramic membrane clear liquid is collected;

[0041] B: The ceramic membrane clear liquid is filtered through an ultrafiltration membrane with a molecular weight cut-off of 800Da, and 52L of ultrafiltration membrane clear liquid is collected;

[0042] C: The ultrafiltration membrane permeate enters a nanofiltration membrane with a molecular weight cut-off of 200 Da, and the obtained nanofiltration membrane concentrate enters a cation exchange resin column at a flow rate of 1 BV / h, the effluent is adjusted to pH 2, and then enters a macroporous decolorizing resin column at a flow rate of 1 BV / h, and the decolorized liquid I is collected, and the decolorized liquid I enters an anion exchange resin column at a flow rate of 1 BV / h, to obtain a desalted liquid 32 L;

[0043] D: The desalted liquid is concentrated to a solid content of 20% w / w at 50°C under vacuum < -0.09 MPa, to obtain a concentrated liquid 12 L;

[0044] E: The concentrated liquid is cooled to 45°C, then 0.1% w / v of pure scyllitol is added as a crystal seed, and then cooled to 35°C at a rate of 0.1°C / h, filtered, and the filter cake and crude crystallization mother liquor 11 L are collected, and the filter cake is rinsed with pure water, to obtain a crude scyllitol 900 g.

[0045] F: The crude scyllitol is dissolved in pure water at 70°C, and the dissolution amount is 3% w / v, after complete dissolution, 2% w / w of activated carbon based on the weight of the crude scyllitol is added for decolorization for 20 min, and after filtration, a decolorized liquid II 30 L is obtained, and the decolorized liquid II is added with a ternary mixed solvent of ethanol-water-ethyl acetate, and after crystallization at 40°C for 0.5 h, the temperature is lowered to 5°C, filtered, to obtain a refined mother liquor 45 L and a filter cake, and the filter cake is dried to obtain a scyllitol product 813 g, with a yield of 90.3% and a purity of 99.8%.

[0046] The addition amount of the ternary mixed solvent is 0.5 times the volume of the decolorized liquid II, and the volume ratio of water, ethanol and ethyl acetate in the ternary mixed solvent is 60:15:15.

[0047] Example 2

[0048] A method for separating and preparing scyllitol, comprising the following steps:

[0049] A: The transformation liquid containing scyllitol (17 g / L) 50 L is warmed to 80°C for inactivation, and after flocculation for 30 min, the temperature is lowered to 30°C, then glacial acetic acid is added to adjust the pH to 4, and 70 ppm of polyaspartic acid salt is further added, and then filtered through a ceramic membrane with a pore size of 30 nm, and the ceramic membrane permeate 50 L is collected;

[0050] B: The ceramic membrane permeate is filtered through an ultrafiltration membrane with a molecular weight cut-off of 900 Da, and the ultrafiltration membrane permeate 51 L is collected;

[0051] C: The ultrafiltration membrane permeate is introduced into a nanofiltration membrane with a molecular weight cut-off of 250 Da, and the obtained nanofiltration membrane concentrate is introduced into a cation exchange resin column at a flow rate of 1.5 BV / h, the effluent is adjusted to pH 3, and then introduced into a macroporous decolorizing resin column at a flow rate of 1.5 BV / h, and the decolorized liquid I is collected; the decolorized liquid I is introduced into an anion exchange resin column at a flow rate of 1.5 BV / h, and the desalted liquid 30 L is obtained;

[0052] D: The desalted liquid is concentrated to a solid content of 25% w / w at 60°C under vacuum of <-0.09 MPa, and the concentrated liquid 10 L is obtained;

[0053] E: The concentrated liquid is cooled to 45°C, and then 0.3% w / v of pure scyllitol is added as a crystal seed, and then cooled to 38°C at a rate of 0.3°C / h, filtered, and the filter cake and the crude crystallization mother liquor 9 L are collected; the filter cake is rinsed with pure water, and the crude scyllitol 850 g is obtained.

[0054] F: The crude scyllitol is dissolved in pure water at 76°C, and the dissolution amount is 4% w / v; after complete dissolution, 4% w / w of activated carbon based on the weight of the crude scyllitol is added for decolorization for 30 min, and the decolorized liquid II 21 L is obtained after filtration; the ternary mixed solvent of ethanol-water-acetone is added to the decolorized liquid II, and the crystal is grown at 50°C for 0.8 h, and then cooled to 10°C; filtered to obtain the refined mother liquor 38 L and the filter cake, which is dried to obtain the finished scyllitol product 762 g, with a yield of 89.6% and a purity of 99.6%.

[0055] The addition amount of the ternary mixed solvent is 0.8 times the volume of the decolorized liquid II, and the volume ratio of water, ethanol and acetone in the ternary mixed solvent is 65:20:20.

[0056] Example 3

[0057] A method for separating and preparing scyllitol, comprising the following steps:

[0058] A: The transformation liquid containing scyllitol (16 g / L) 50 L is warmed to 90°C for inactivation, cooled to 30°C after flocculation for 30 min, and then adjusted to pH 5 by adding glacial acetic acid; 100 ppm of polyaspartic acid salt is further added, and then filtered through a ceramic membrane with a pore size of 50 nm, and the ceramic membrane permeate 50 L is collected;

[0059] B: The ceramic membrane permeate is filtered through an ultrafiltration membrane with a molecular weight cut-off of 1000 Da, and the ultrafiltration membrane permeate 52 L is collected;

[0060] C: The ultrafiltration membrane permeate enters a nanofiltration membrane with a molecular weight cut-off of 300 Da, and the obtained nanofiltration membrane concentrate enters a cation exchange resin column at a flow rate of 2 BV / h, the effluent is adjusted to pH 3, and then enters a macroporous decolorizing resin column at a flow rate of 2 BV / h, and the decolorized liquid I is collected, and the decolorized liquid I enters an anion exchange resin column at a flow rate of 2 BV / h, to obtain a desalted liquid 31 L;

[0061] D: The desalted liquid is concentrated to a solid content of 30% w / w at 70°C under vacuum < -0.09 MPa, to obtain a concentrated liquid 8.5 L;

[0062] E: The concentrated liquid is cooled to 45°C, then 0.5% w / v of pure scyllitol is added as a crystal seed, and then cooled to 40°C at a rate of 0.5°C / h, filtered, and the filter cake and crude crystallization mother liquor 7 L are collected, and the filter cake is rinsed with pure water, to obtain a crude scyllitol 800 g.

[0063] F: The crude scyllitol is dissolved in pure water at 80°C, and the dissolution amount is 5% w / v, after complete dissolution, 5% w / w of activated carbon based on the weight of the crude scyllitol is added for decolorization for 40 min, and after filtration, a decolorized liquid II 16 L is obtained, and the decolorized liquid II is added with a ternary mixed solvent of ethanol-water-ethyl acetate, and after crystallization at 60°C for 1 h, the temperature is lowered to 15°C, filtered, to obtain a refined mother liquor 32 L and a filter cake, and the filter cake is dried to obtain a finished scyllitol product 706 g, with a yield of 88.3% and a purity of 99.7%.

[0064] The addition amount of the ternary mixed solvent is 1 times the volume of the decolorized liquid II, and the volume ratio of water, ethanol and ethyl acetate in the ternary mixed solvent is 70:25:25.

[0065] Example 4

[0066] A method for separating and preparing scyllitol, comprising the following steps:

[0067] A: The transformation liquid containing scyllitol (15 g / L) 50 L is warmed to 85°C for inactivation, and after flocculation for 30 min, the temperature is lowered to 30°C, then glacial acetic acid is added to adjust the pH to 4, and 100 ppm of polyaspartic acid salt is further added, and then filtered through a ceramic membrane with a pore size of 50 nm, and the ceramic membrane permeate 50 L is collected;

[0068] B: The ceramic membrane permeate is filtered through an ultrafiltration membrane with a molecular weight cut-off of 1000 Da, and the ultrafiltration membrane permeate 53 L is collected;

[0069] C: The superfiltration membrane supernatant enters a nanofiltration membrane with a molecular weight cutoff of 250 Da. The resulting nanofiltration membrane concentrate enters a cation exchange resin column at a flow rate of 1.5 BV / h. The effluent is adjusted to pH 3 and then enters a macroporous decolorizing resin column at a flow rate of 2 BV / h. Decolorized solution I is collected and then enters an anion exchange resin column at a flow rate of 1.5 BV / h to obtain 34 L of desalination solution.

[0070] D: The desalination solution was concentrated at 65℃ and under vacuum < -0.09MPa until the solid content of the feed solution was 28% w / w, yielding 9L of concentrate;

[0071] E: Cool the concentrate to 45°C, then add 0.4% w / v of pure squalene as seed crystals, and then cool to 38°C at a rate of 0.3°C / h. Filter, collect the filter cake and 8L of crude crystallization mother liquor. Rinse the filter cake with pure water to obtain 750g of crude squalene.

[0072] F: Crude squalene was dissolved in pure water at 78°C with a dissolution rate of 4% w / v. After complete dissolution, activated carbon at 5% w / w of the crude squalene weight was added for decolorization for 40 min. After filtration, 19 L of decolorized solution II was obtained. A ternary mixed solvent of ethanol-water-ethyl acetate was added to decolorized solution II. Crystallization was carried out at 60°C for 1 h, and then cooled to 5°C for crystallization. After filtration, 34 L of purified mother liquor and filter cake were obtained. The filter cake was dried to obtain 650 g of squalene product, with a yield of 86.7% and a purity of 99.6%.

[0073] The amount of the ternary mixed solvent added accounts for 0.8 times the volume of decolorizing solution II, and the volume ratio of water, ethanol and acetone in the ternary mixed solvent is 65:25:15.

[0074] It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A method for separating and preparing squalene, characterized in that... Includes the following steps: A: The conversion solution containing squalene is heated to inactivate it, then glacial acetic acid is added to adjust the pH to 3-5, and after filtration through a ceramic membrane, the clear liquid from the ceramic membrane is collected. B: Pass the supernatant through the ceramic membrane through the ultrafiltration membrane and collect the supernatant from the ultrafiltration membrane; C: The superfiltration membrane supernatant enters the cation exchange resin column, the effluent pH is adjusted to 2-3, and then it enters the macroporous decolorizing resin column. Decolorized solution I is collected, and decolorized solution I then enters the anion exchange resin column to obtain the desalination solution. D: The desalination solution is concentrated at 50-70℃ and under vacuum <-0.09MPa until the solid content of the liquid is 20-30% w / w to obtain the concentrate; E: Cool the concentrate to 45°C, then add pure squalene as seed crystals, and then cool to 35-40°C at a rate of 0.1-0.5°C / h. Filter, collect the filter cake and crude crystallization mother liquor, and wash the filter cake with pure water to obtain crude squalene.

2. The method for separating and preparing squalene as described in claim 1, characterized in that: The inactivation temperature in step A is 70-90℃. After inactivation, flocculation is performed for 30 minutes. Then, the temperature is lowered to 30℃, glacial acetic acid is added to adjust the pH, and 50-100 ppm of polyaspartic acid salt is added. Then, the mixture is filtered through a ceramic membrane.

3. The method for separating and preparing squalene as described in claim 1, characterized in that: The ceramic membrane has a filtration pore size of 20-50 nm, and the ultrafiltration membrane has a molecular weight cutoff of 800-1000 Da.

4. The method for separating and preparing squalene as described in claim 1, characterized in that: The ultrafiltration membrane supernatant from step C enters the nanofiltration membrane, and the resulting nanofiltration membrane supernatant enters the cation exchange resin column, wherein the molecular weight cutoff of the nanofiltration membrane is 200-300 Da; The feed rates for the cation exchange resin column, macroporous decolorizing resin column, and anion exchange resin column are all 1-2 BV / h.

5. The method for separating and preparing squalene as described in claim 1, characterized in that: The crude crystallization mother liquor from step E is returned to the conversion solution containing squalene and the operation of step A is repeated. The amount of pure squalene added as seed crystals is 0.1-0.5% w / v of the volume of the concentrate.

6. The method for separating and preparing squalene as described in claim 1, characterized in that: Crude squalene is dissolved in pure water. After complete dissolution, activated carbon is added for decolorization. The resulting decolorized solution II is then added to a ternary mixed solvent of ethanol-water-ethyl acetate or ethanol-water-acetone. After crystal growth, the solution is cooled and crystallized. The solution is then filtered to obtain a purified mother liquor and a filter cake. The filter cake is dried to obtain the finished squalene product.

7. The method for separating and preparing squalene as described in claim 6, characterized in that: Crude squalene is dissolved in pure water at 70-80℃, with a dissolution rate of 3-5% w / v. The amount of activated carbon added is 2-5% w / w of the weight of crude squalene, and the decolorization time is 20-40 min.

8. The method for separating and preparing squalene as described in claim 6, characterized in that: The amount of the ternary mixed solvent added is 0.5-1 times the volume of decolorizing solution II. The volume ratio of water, ethanol and ethyl acetate / acetone in the ternary mixed solvent is 60-70:15-25:15-25.

9. The method for separating and preparing squalene as described in claim 6, characterized in that: The crystal growth temperature is 40-60℃, the crystal growth time is 0.5-1h, and the temperature is lowered to 5-15℃ after crystal growth.

10. The method for separating and preparing squalene as described in claim 6, characterized in that: The refined mother liquor is recycled for dissolving crude squalene.

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