Preparation method of glucurolactone

Abstract

The invention discloses a glucurolactone preparation method, and relates to the technical field of pharmacy, the glucurolactone preparation method comprises the following steps: taking an inositol solution, adding into whole cells containing inositol oxidase, transforming, adjusting the pH value to 7.0-8.0, filtering the obtained transformation liquid through a ceramic membrane and an ultrafiltration membrane, desalting through cation exchange resin, concentrating the desalted liquid through a nanofiltration membrane, and drying to obtain glucurolactone. The nanofiltration membrane concentrated solution is concentrated in a concentrator under the vacuum lower than-0.09 Mpa, the temperature of a liquid phase in the concentrator is controlled to be 50-60 DEG C, after concentration is finished, the stirring rotating speed is controlled to be 50-200 rpm, the temperature of the liquid phase is increased to 70-80 DEG C, then a decolorizing agent is added for decolorizing for 20-40 min, a decolorizing solution is collected, cooled to 10-20 DEG C, filtered and washed with cold water at the temperature of 2-4 DEG C, and glucurolactone crystals are obtained. Glacial acetic acid or other catalysts are not added in the esterification process, so that the process is simplified, the production cost is greatly reduced, and the production period is shortened.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceuticals, and in particular to a method for preparing glucuronolactone. Background Art

[0002] The full name of glucuronolactone in Chinese is glucuronolactone, commonly known as liver taylor, with the molecular formula of C6H8O6, and its chemical composition is: D(+)-furanoglucuronic acid γ-lactone, English name: [D(+)-Glucofuranurono-6,3-lactone]. As a liver detoxifier and immune function regulator, glucuronolactone is a conventional liver protection medicine; glucuronolactone and its subsequent products are also the main additives of functional beverages and foods, weight loss drugs, cosmetics, etc., which have the effects of replenishing physical energy, improving hypoxia, nourishing skin, and delaying aging.

[0003] The main method for industrial production of glucuron-lactone at present is the nitric acid oxidation method starting from starch. The process is as follows: starch is added to nitric acid with a content of about 80% (V / V) to oxidize to obtain oxidized starch, the starch oxidation solution is heated and pressurized under acidic conditions to hydrolyze to obtain the hydrolyzate of oxidized starch, the hydrolyzate is concentrated under reduced pressure to a Baume degree of 44-49, acetic acid is added for esterification, the esterification mixture is cooled to 30-45°C and allowed to stand for 16-20h, then concentrated under reduced pressure to a Baume degree of 40-45, and gradually cooled to -4 to -8°C. The total cooling and crystallization time is generally 70-80h, and the crystals are filtered by high-speed centrifugation to obtain a crude glucuron-lactone product with a purity of 80-90%. The yield of glucuron lactone obtained by this process is low, and its yield is only about 14%; acetic acid is added in the production process of glucuron lactone, and acetic acid is easy to corrode equipment, and the equipment control requirements are strict. The energy consumption in the production process is large and it is difficult to recover acetic acid; and the crude product extraction process has large losses, the production cost is high, it is difficult to meet the needs of the market, and it is also highly polluting to the environment. Summary of the invention

[0004] The technical problem to be solved by the present invention is: in view of the deficiencies in the prior art, a method for preparing glucuron lactone is provided, which has high glucuron lactone yield and low production cost.

[0005] In order to solve the above technical problems, the technical solution of the present invention is:

[0006] A method for preparing glucuronolactone comprises the following steps:

[0007] A: Take the inositol solution and add the whole cells containing inositol oxidase for transformation. During the transformation process, add ammonia water to adjust the pH to 7.0-8.0 to obtain the transformation solution;

[0008] B: The conversion liquid is filtered through a ceramic membrane, and the ceramic membrane clear liquid is collected;

[0009] C: The ceramic membrane clear liquid is filtered through an ultrafiltration membrane to collect the ultrafiltration membrane clear liquid;

[0010] D: The ultrafiltration membrane clear liquid enters the cation exchange resin for desalination, and the desalted liquid is collected;

[0011] E: The desalted liquid is concentrated by nanofiltration membrane to obtain nanofiltration membrane concentrate;

[0012] F: The nanofiltration membrane concentrate is concentrated in a concentrator under vacuum <-0.09Mpa, and the liquid temperature in the concentrator is controlled to be 50-60°C. After the concentration is completed, the stirring speed is controlled to 50-200rpm and the liquid temperature is raised to 70-80°C, and then a decolorizing agent is added to decolorize for 20-40 minutes. The decolorized liquid is collected, cooled to 10-20°C, filtered, and washed with 2-4°C cold water to obtain glucuron-lactone crystals.

[0013] Preferably, the concentration of the inositol solution in step A is 10-150 g / L, and the whole cells containing inositol oxidase are system OD 600 =10-50, conversion time is 2-6h.

[0014] Preferably, the pore size of the ceramic membrane in step B is 50-100 nm.

[0015] Preferably, the pore size of the ultrafiltration membrane in step C is 1000-10000Da.

[0016] Preferably, the flow rate of the ultrafiltration membrane clear liquid into the column in step D is 1-2 BV / h.

[0017] Preferably, in step E, the desalted liquid is concentrated to a solid content of 15-20% w / w by a nanofiltration membrane, and the pore size of the nanofiltration membrane is 150-200 Da.

[0018] Preferably, in step F, the nanofiltration membrane concentrate is concentrated in a concentrator to a solid content of 50-70% w / w.

[0019] Preferably, after the concentration in step F is completed, the material is kept at 70-80° C. for 1-2 hours.

[0020] Preferably, in step F, the decolorizing agents are activated carbon and diatomaceous earth, wherein the amount of activated carbon added is 2-3% of the volume of the feed liquid, and the amount of diatomaceous earth added is 1-2% of the volume of the feed liquid.

[0021] Preferably, the cooling rate of the decolorizing solution in step F is 1-5°C / h.

[0022] Due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0023] 1. Compared with the prior art, glacial acetic acid or other catalysts are not added during the esterification process, glucuronic acid is esterified to generate glucuronolactone by high temperature, and no concentration and dehydration are required after esterification. Glucuronolactone crystals can be obtained by cooling and crystallizing, which simplifies the process, greatly reduces the production cost, and shortens the production cycle.

[0024] 2. Since no other catalysts and dehydrating agents are added during the esterification process, the finished product can be obtained directly without the need to recycle glacial acetic acid or other catalysts, thus saving production costs, being more conducive to environmentally friendly production, and being environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is the liquid chromatogram of glucuronolactone in Example 1 of the present invention. DETAILED DESCRIPTION

[0026] The present invention will be further described below in conjunction with the embodiments.

[0027] Example 1

[0028] A method for preparing glucuronolactone comprises the following steps:

[0029] A: Take 100L of 10g / L inositol solution and add whole cells containing inositol oxidase for transformation for 2h. During the transformation, add ammonia water to adjust the pH to 7.0 to obtain 104L of transformation solution, of which whole cells containing inositol oxidase are the system OD 600 =10;

[0030] B: The conversion liquid is filtered through a ceramic membrane, and 100L of the ceramic membrane clear liquid is collected. The pore size of the ceramic membrane is 50nm, and the ceramic membrane concentrated liquid is treated for environmentally friendly sewage discharge;

[0031] C: The ceramic membrane clear liquid is filtered through an ultrafiltration membrane to collect 95L of ultrafiltration membrane clear liquid, the pore size of the ultrafiltration membrane is 1000Da, and the ultrafiltration membrane concentrate is treated for environmentally friendly sewage discharge;

[0032] D: The ultrafiltration membrane clear liquid enters the cation exchange resin for desalination, and 95L of desalted liquid is collected. The flow rate of the ultrafiltration membrane clear liquid into the column is 1BV / h;

[0033] E: The desalted liquid was concentrated to a solid content of 15% w / w through a nanofiltration membrane to obtain 6.7 L of nanofiltration membrane concentrate. The pore size of the nanofiltration membrane was 150 Da.

[0034] F: The nanofiltration membrane concentrate was concentrated in a concentrator under vacuum <-0.09Mpa, the liquid temperature in the concentrator was controlled at 50°C, and concentrated to a solid content of 50% w / w. After the concentration was completed, the stirring speed was controlled to 50rpm and the liquid temperature was raised to 70°C and kept warm for 1h. Then, a decolorizing agent was added to decolorize for 20min, 1.7L of the decolorized liquid was collected, cooled to 10°C at a rate of 1°C / h, filtered, and washed with 2°C cold water to obtain 810g of glucuron-lactone crystals with a content of 99.3% and a total yield of 82.8%.

[0035] Example 2

[0036] A method for preparing glucuronolactone comprises the following steps:

[0037] A: Take 100L of 70g / L inositol solution and add whole cells containing inositol oxidase for transformation for 4h. During the transformation, add ammonia water to adjust the pH to 7.0 to obtain 113L of transformation solution, of which whole cells containing inositol oxidase are the system OD 600 =30;

[0038] B: The conversion liquid is filtered through a ceramic membrane, and 109L of the ceramic membrane clear liquid is collected. The pore size of the ceramic membrane is 70nm, and the ceramic membrane concentrated liquid is treated for environmentally friendly sewage discharge;

[0039] C: The ceramic membrane clear liquid is filtered through an ultrafiltration membrane to collect 103L of ultrafiltration membrane clear liquid, the pore size of the ultrafiltration membrane is 5000Da, and the ultrafiltration membrane concentrate is treated for environmentally friendly sewage discharge;

[0040] D: The ultrafiltration membrane clear liquid enters the cation exchange resin for desalination, and 103L of desalted liquid is collected. The flow rate of the ultrafiltration membrane clear liquid into the column is 1.5BV / h;

[0041] E: The desalted liquid was concentrated to a solid content of 18% w / w through a nanofiltration membrane to obtain 38 L of nanofiltration membrane concentrate. The pore size of the nanofiltration membrane was 150 Da.

[0042] F: The nanofiltration membrane concentrate was concentrated in a concentrator under vacuum <-0.09Mpa, the liquid temperature in the concentrator was controlled at 55°C, and concentrated to a solid content of 55% w / w. After the concentration was completed, the stirring speed was controlled to 80rpm and the liquid temperature was raised to 75°C and kept warm for 1.5h. Then, a decolorizing agent was added to decolorize for 30min, 11L of the decolorized liquid was collected, cooled to 15°C at a rate of 3°C / h, filtered, and washed with 3°C cold water to obtain 5800g of glucuron-lactone crystals with a content of 99.5% and a total yield of 84.7%.

[0043] Example 3

[0044] A method for preparing glucuronolactone comprises the following steps:

[0045] A: Take 100L of 100g / L inositol solution and add whole cells containing inositol oxidase for transformation for 5h. During the transformation, add ammonia water to adjust the pH to 8.0 to obtain 121L of transformation solution, of which whole cells containing inositol oxidase are the system OD 600 =40;

[0046] B: The conversion liquid is filtered through a ceramic membrane, and 116L of the ceramic membrane clear liquid is collected. The pore size of the ceramic membrane is 80nm, and the ceramic membrane concentrated liquid is treated for environmentally friendly sewage discharge;

[0047] C: The ceramic membrane clear liquid is filtered through an ultrafiltration membrane to collect 109L of ultrafiltration membrane clear liquid, the pore size of the ultrafiltration membrane is 8000Da, and the ultrafiltration membrane concentrate is treated for environmentally friendly sewage discharge;

[0048] D: The ultrafiltration membrane clear liquid enters the cation exchange resin for desalination, and 109L of desalted liquid is collected. The flow rate of the ultrafiltration membrane clear liquid into the column is 2BV / h;

[0049] E: The desalted liquid was concentrated to a solid content of 19% w / w through a nanofiltration membrane to obtain 52 L of nanofiltration membrane concentrate. The pore size of the nanofiltration membrane was 200 Da.

[0050] F: The nanofiltration membrane concentrate was concentrated in a concentrator under vacuum <-0.09Mpa, the liquid temperature in the concentrator was controlled at 58°C, and concentrated to a solid content of 65% w / w. After the concentration was completed, the stirring speed was controlled at 150rpm and the liquid temperature was raised to 78°C and kept warm for 2h. Then, a decolorizing agent was added to decolorize for 35min, 14L of the decolorized liquid was collected, cooled to 18°C ​​at a rate of 4°C / h, filtered, and washed with 3°C cold water to obtain 8300g of glucuron-lactone crystals with a content of 99.3% and a total yield of 84.9%.

[0051] Example 4

[0052] A method for preparing glucuronolactone comprises the following steps:

[0053] A: Take 100L of 150g / L inositol solution and add whole cells containing inositol oxidase for transformation for 6h. During the transformation, add ammonia water to adjust the pH to 8.0 to obtain 129L of transformation solution, of which whole cells containing inositol oxidase are the system OD 600 =50;

[0054] B: The conversion liquid was filtered through a ceramic membrane, and 126L of the ceramic membrane clear liquid was collected. The pore size of the ceramic membrane was 100nm, and the ceramic membrane concentrated liquid was treated for environmentally friendly sewage discharge;

[0055] C: The ceramic membrane clear liquid is filtered through an ultrafiltration membrane to collect 121L of ultrafiltration membrane clear liquid, the pore size of the ultrafiltration membrane is 10000Da, and the ultrafiltration membrane concentrate is treated for environmentally friendly sewage discharge;

[0056] D: The ultrafiltration membrane clear liquid enters the cation exchange resin for desalination, and 121L of desalted liquid is collected. The flow rate of the ultrafiltration membrane clear liquid into the column is 2BV / h;

[0057] E: The desalted liquid is concentrated to a solid content of 20% w / w through a nanofiltration membrane to obtain 75 L of nanofiltration membrane concentrate. The pore size of the nanofiltration membrane is 200 Da.

[0058] F: The nanofiltration membrane concentrate was concentrated in a concentrator under vacuum <-0.09Mpa, and the liquid temperature in the concentrator was controlled at 60°C. The concentrate was concentrated to a solid content of 70% w / w. After the concentration was completed, the stirring speed was controlled at 200rpm and the liquid temperature was raised to 80°C and kept warm for 2h. Then, a decolorizing agent was added to decolorize for 40min. 18L of the decolorized liquid was collected, cooled to 20°C at a rate of 5°C / h, filtered, and washed with cold water at 4°C to obtain 12100g of glucuron-lactone crystals with a content of 99.4% and a total yield of 82.5%.

[0059] It should be understood that these embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope limited by the appended claims of the application.

Claims

1. A method for preparing glucuronolactone, characterized in that The following steps are involved: A: Take the inositol solution and add the whole cells containing inositol oxidase for transformation. During the transformation process, add ammonia water to adjust the pH to 7.0-8.0 to obtain the transformation solution; B: The conversion liquid is filtered through a ceramic membrane, and the ceramic membrane clear liquid is collected; C: The ceramic membrane clear liquid is filtered through an ultrafiltration membrane to collect the ultrafiltration membrane clear liquid; D: The ultrafiltration membrane clear liquid enters the cation exchange resin for desalination, and the desalted liquid is collected; E: The desalted liquid is concentrated by nanofiltration membrane to obtain nanofiltration membrane concentrate; F: The nanofiltration membrane concentrate is concentrated in a concentrator under vacuum <-0.09Mpa, and the liquid temperature in the concentrator is controlled to be 50-60°C. After the concentration is completed, the stirring speed is controlled to 50-200rpm and the liquid temperature is raised to 70-80°C, and then a decolorizing agent is added to decolorize for 20-40 minutes. The decolorized liquid is collected, cooled to 10-20°C, filtered, and washed with 2-4°C cold water to obtain glucuron-lactone crystals.

2. A method for preparing glucuronolactone according to claim 1, characterized in that: The concentration of the inositol solution in step A is 10-150 g / L, and the whole cells containing inositol oxidase are the system OD 600 =10-50, conversion time is 2-6h.

3. A method for preparing glucuronolactone according to claim 1, characterized in that: The pore size of the ceramic membrane in step B is 50-100 nm.

4. A method for preparing glucuronolactone according to claim 1, characterized in that: The pore size of the ultrafiltration membrane in step C is 1000-10000Da.

5. A method for preparing glucuronolactone according to claim 1, characterized in that: The column flow rate of the ultrafiltration membrane clear liquid in step D is 1-2 BV / h.

6. A method for preparing glucuronolactone according to claim 1, characterized in that: In step E, the desalted liquid is concentrated to a solid content of 15-20% w / w by a nanofiltration membrane, and the pore size of the nanofiltration membrane is 150-200 Da.

7. A method for preparing glucuronolactone according to claim 1, characterized in that: In step F, the nanofiltration membrane concentrate is concentrated in a concentrator to a solid content of 50-70% w / w.

8. A method for preparing glucuronolactone according to claim 1, characterized in that: After the concentration in step F is completed, the material is kept at 70-80°C for 1-2 hours.

9. A method for preparing glucuronolactone according to claim 1, characterized in that: In step F, the decolorizing agents are activated carbon and diatomaceous earth, wherein the amount of activated carbon added is 2-3% of the volume of the feed liquid, and the amount of diatomaceous earth added is 1-2% of the volume of the feed liquid.

10. The method for preparing glucuronolactone according to claim 1, characterized in that: The cooling rate of the decolorizing solution in step F is 1-5°C / h.

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