Preparation method and application of (R)-3-hydroxybutyric acid solid based on adsorbent

Abstract

The invention belongs to the technical field of biological medicine, and provides a preparation method and application of (R)-3-hydroxybutyric acid solid based on an adsorbent. The method comprises the following steps: diluting an (R)-3-hydroxybutyric acid solution by using absolute ethyl alcohol to reduce the combination of (R)-3-hydroxybutyric acid and water molecules, then adsorbing and completely dehydrating by using a food-grade silicon dioxide adsorbent, filtering to remove the adsorbent, and drying to remove ethyl alcohol to obtain an (R)-3-hydroxybutyric acid solid. The optical purity of the obtained (R)-3-hydroxybutyric acid solid reaches 95.04%-95.14%, the mass fraction reaches 97.06 wt%-98.05 wt%, the yield reaches 82.1%-90.8%, the (R)-3-hydroxybutyric acid solid can be obtained, the yield is high, and no harmful impurities are generated.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biological medicine, more particularly, to a preparation method of (R)-3-hydroxybutyric acid solid based on adsorbent and application thereof. BACKGROUND

[0002] 3-hydroxybutyric acid (3-HB) is a monomer form of natural polymer poly(R)-3-hydroxybutyric acid (hereinafter referred to as PHB), which exists in pure R configuration in a natural state. As an important ketone body in vivo, 3-hydroxybutyric acid is produced by degradation of long-chain fatty acids in the liver, transported to peripheral tissues through blood, and regulates the function of the body. 3-hydroxybutyric acid has great application value and prospect in the health care, food and pharmaceutical industries, including: accelerating weight loss; stimulating the expression of various health-promoting genes; reducing the incidence of inflammatory complications; improving exercise performance and training efficiency; enhancing metabolic efficiency; providing optimal energy for the heart, reducing the incidence of cardiovascular disease; improving insulin sensitivity; preventing cancer and related diseases caused by glucose metabolism disorders; improving cognitive ability, preventing senile dementia, and prolonging life, etc.

[0003] At present, the preparation of high-content (R)-3-hydroxybutyric acid crystals mainly uses chemical synthesis method (also known as liquid phase oxidation method), which uses 3-hydroxybutyraldehyde and oxygen as main raw materials, cobalt acetate as catalyst, and ethyl acetate as solvent to synthesize (R)-3-hydroxybutyric acid under certain temperature and pressure, involving the main reaction as follows:

[0004] 2CH3CH(OH)CH2CHO+O2→2CH3CH(OH)CH2COOH;

[0005] The side reactions involved are as follows:

[0006] CH3CH(OHCH2CHO→CH3CH=CHCHO+H2O

[0007] 2CH3CH=CHCHO+O2→2CH3CH=CHCOOH

[0008]

[0009] After the above reaction is completed, the relatively low boiling point ethyl acetate and 3-hydroxybutyraldehyde are removed by concentration, but the high boiling point butenoic acid (3-butenoic acid and 2-butenoic acid) produced by the side reaction and the catalyst cobalt acetate are relatively difficult to remove, especially the catalyst cobalt acetate. Moreover, cobalt and cobalt compounds are carcinogens. Therefore, the 3-hydroxybutyric acid crystal directly synthesized by this method has residual by-products and cobalt acetate, which has great safety hazards and is not suitable for application in the field of food or health care products.

[0010] (R)-3-hydroxybutyric acid is another mainstream method for preparing PHB degradation method, mainly has the following three routes: (1) base degradation method: first using strong base hydrolysis PHB to prepare 3-hydroxybutyric acid salt, then using acid neutralization, prepare (R)-3-hydroxybutyric acid. (2) acid catalytic hydrolysis method: using acid catalytic hydrolysis PHB to prepare (R)-3-hydroxybutyric acid. (3) PHB is first alcoholysis to produce 3-hydroxybutyrate, 3-hydroxybutyrate is hydrolyzed to prepare 3-hydroxybutyric acid. The above three methods, although avoid the high content 3-hydroxybutyric acid crystal of the impurities brought by the direct synthesis of chemical method, but the prepared 3-hydroxybutyric acid product is low content (generally the mass fraction of 3-hydroxybutyric acid in the product is less than 50wt%) 3-hydroxybutyric acid aqueous solution, if the above prepared 3-hydroxybutyric acid aqueous solution is directly concentrated, one is that 3-hydroxybutyric acid contains hydroxyl and carboxyl polar group, can be combined with water molecule through hydrogen bond, leading to water molecule difficult to evaporate and remove, in addition, in the later stage of concentration, the viscosity of the system is large, leading to the mass fraction of 3-hydroxybutyric acid difficult to reach more than 80%, still is liquid material;Two is that when the content is concentrated to more than 60%, the probability of condensation dehydration reaction of 3-hydroxybutyric acid increases, forming part of 3-hydroxybutyric acid ester oligomer (byproduct), and the system is further viscous, and the water is more difficult to remove. And in order to prevent deterioration, prolong the shelf life, reduce the volume and facilitate carrying and transportation, generally requires the water content of solid beverage to be less than 5wt%. Therefore, the existing (R)-3-hydroxybutyric acid product is difficult to be applied in solid preparation, which greatly limits the industrial production and application of the product in preparing solid beverage and other solid products.

[0011] And the commercially available (R)-3-hydroxybutyric acid is mainly in the form of solid powder of its salt, mainly sodium salt, magnesium salt and calcium salt. This form is simple to prepare and can be widely used in various solid preparations. When the amount of (R)-3-hydroxybutyric acid salt is large, the salt intake is high, which is not conducive to human health.

[0012] Therefore, it is urgent to develop a preparation method of (R)-3-hydroxybutyric acid solid without harmful impurities and with low water content. SUMMARY

[0013] The present application aims to at least solve one of the technical problems existing in the prior art. To this end, the present application provides a preparation method of (R)-3-hydroxybutyric acid solid based on adsorbent and its application. The method provided by the present application can not only prepare (R)-3-hydroxybutyric acid solid, but also has a mass fraction of (R)-3-hydroxybutyric acid of 97.06-98.05wt%, a high yield (which can reach 82.1-90.8%), and does not need to use harmful raw materials (such as catalyst cobalt acetate), and the product does not contain harmful impurities, which is healthy and safe.

[0014] The first aspect of the present application provides a method for preparing a (R)-3-hydroxybutyric acid solid based on an adsorbent.

[0015] Specifically, the method for preparing a (R)-3-hydroxybutyric acid solid based on an adsorbent comprises the following steps:

[0016] (1) Taking a (R)-3-hydroxybutyric acid solution, adding ethanol to dilute it to a solute mass fraction of 15%-35% to obtain a diluted solution;

[0017] (2) Using an adsorbent to adsorb and dehydrate the diluted solution, and then removing the adsorbent to obtain a dehydrated solution;

[0018] (3) Drying the dehydrated solution to obtain the (R)-3-hydroxybutyric acid solid.

[0019] The present application uses a (R)-3-hydroxybutyric acid solution as a raw material, adds ethanol for dilution, reduces the combination of (R)-3-hydroxybutyric acid and water molecules, and then uses a food-grade silicon dioxide adsorbent to completely dehydrate. In the presence of ethanol, it is helpful for the adsorption of water molecules by the adsorbent. The reason may be that water molecules are more easily exposed in the solution system, improving the contact probability of the adsorbent and water molecules. After removing the adsorbent, the ethanol is then removed by drying to obtain a (R)-3-hydroxybutyric acid solid with low water content. In addition, ethanol can be recovered by condensation, and silicon dioxide adsorbent can be recovered by drying and reused, reducing costs. Without using harmful raw materials (such as cobalt acetate catalyst), the (R)-3-hydroxybutyric acid solid product is healthier and safer. The (R)-3-hydroxybutyric acid solid preparation method provided by the present application not only overcomes the problem of low safety of 3-hydroxybutyric acid solid prepared by traditional chemical synthesis method, but also overcomes the problem of difficulty in preparing 3-hydroxybutyric acid solid with low water content by PHB degradation method.

[0020] Preferably, in step (1), the (R)-3-hydroxybutyric acid solution is not chemically synthesized (such as the (R)-3-hydroxybutyric acid solution prepared in Chinese Patent Publication No. CN112961049A, or the food-grade (R)-3-hydroxybutyric acid solution with model number D3HB50 produced by Zhuhai Maidegen Biotechnology Co., Ltd.). Chemical synthesis of (R)-3-hydroxybutyric acid requires the use of toxic raw materials (such as cobalt acetate).

[0021] Preferably, in step (1), the solute mass fraction of the (R)-3-hydroxybutyric acid solution is 40-55wt%.

[0022] Further preferably, in step (1), the solute mass fraction of the (R)-3-hydroxybutyric acid solution is 45-50wt%.

[0023] Preferably, in step (1), the (R)-3-hydroxybutyric acid solution is heated and concentrated at 45-55℃ to a solute mass fraction of 40-55wt%.

[0024] Further preferably, in step (1), the (R)-3-hydroxybutyric acid solution is heated and concentrated at 50-55℃ to a solute mass fraction of 40-55wt%.

[0025] Preferably, in step (1), ethanol is added to dilute to a solute mass fraction of 20%-30%.

[0026] Preferably, in step (1), the volume fraction of the ethanol is 90-99%.

[0027] Preferably, in step (2), the adsorbent is a silica adsorbent. The silica adsorbent has a fast adsorption speed and does not chemically react with (R)-3-hydroxybutyric acid and is insoluble in (R)-3-hydroxybutyric acid aqueous solution.

[0028] Further preferably, in step (2), the silica adsorbent is a food-grade silica adsorbent and does not contain cobalt chloride.

[0029] Preferably, in step (2), the adsorption dehydration does not cause the adsorbent to discolor.

[0030] Preferably, in step (2), the removal of the adsorbent is by filtration, the filter residue is removed, and the filtrate is taken.

[0031] Preferably, the filtration is suction filtration.

[0032] Preferably, in step (2), after the adsorption dehydration, the adsorbent is washed and dried, and the adsorbent is recovered. The adsorbent can be recovered and reused.

[0033] Preferably, the adsorbent is washed and dried at 100-110℃ to a constant weight, and the adsorbent is recovered.

[0034] Preferably, in step (3), the drying is vacuum drying.

[0035] Preferably, in step (3), the vacuum drying is at a pressure of -0.09--0.1mPa, and / or the vacuum drying is at a temperature of 35-45℃, and / or the vacuum drying is for a time of 5-10h. The low-temperature drying removes ethanol and avoids the formation of oligomers.

[0036] Further preferably, in step (3), the vacuum drying is at a pressure of -0.095--0.1mPa, and / or the vacuum drying is at a temperature of 35-40℃, and / or the vacuum drying is for a time of 8-10h.

[0037] Preferably, in step (3), after drying, the ethanol is condensed and recovered. The ethanol can be recovered and reused.

[0038] Preferably, in step (3), the mass fraction of (R)-3-hydroxybutyric acid in the (R)-3-hydroxybutyric acid solid is 97-99wt%. The (R)-3-hydroxybutyric acid solid prepared by the present application has very low moisture and impurity content, and the mass content of (R)-3-hydroxybutyric acid is as high as 97-99wt%.

[0039] Further preferably, in step (3), the mass fraction of (R)-3-hydroxybutyric acid in the (R)-3-hydroxybutyric acid solid is 97-98.5wt%.

[0040] The second aspect of the present application provides an application of a preparation method of (R)-3-hydroxybutyric acid solid based on an adsorbent.

[0041] The application of a preparation method of (R)-3-hydroxybutyric acid solid based on an adsorbent in the preparation of solid food containing (R)-3-hydroxybutyric acid.

[0042] Compared with the prior art, the present application has the following beneficial effects:

[0043] In the present application, (R)-3-hydroxybutyric acid solution is first diluted with anhydrous ethanol to reduce the combination of (R)-3-hydroxybutyric acid and water molecules, and then a food-grade silica adsorbent is used for adsorption to completely remove water molecules. In the presence of ethanol, water molecules are more easily exposed in the solution system, which improves the contact probability of the adsorbent and water molecules, and helps the adsorption of the adsorbent to water molecules. Then, the adsorbent is removed by filtration, and the ethanol is removed by drying to obtain (R)-3-hydroxybutyric acid solid. The optical purity of the (R)-3-hydroxybutyric acid solid prepared by the present application reaches 95.04-95.14%, the mass fraction reaches 97.06-98.05wt%, and the yield reaches 82.1-90.8%. Not only (R)-3-hydroxybutyric acid solid can be obtained, but also the yield is high and no harmful impurities are generated. DETAILED DESCRIPTION

[0044] In order to make the skilled in the art more clearly understand the technical solutions described in the present application, the following examples are given for illustration. It should be pointed out that the following examples do not constitute a limitation on the scope of protection required by the present application.

[0045] The raw materials, reagents or devices used in the following examples are commercially available or can be obtained by known methods unless otherwise specified.

[0046] The raw materials used in the examples and comparative examples of the present application are as follows:

[0047] (R)-3-hydroxybutyric acid solution: solute mass fraction 40.0 wt%, produced by Zhuhai Maidehuan Biotechnology Co., Ltd., model D3HB50, food grade.

[0048] Ethanol: food grade 95% ethanol, ethanol volume fraction 95%.

[0049] Example 1

[0050] A method for preparing (R)-3-hydroxybutyric acid solid based on adsorbent, comprising the following steps:

[0051] (1) Take 100 g of (R)-3-hydroxybutyric acid solution, add 33.3 g of food grade 95% ethanol, and dilute to a solute mass fraction of 30.0 wt%.

[0052] (2) Add 50 g of food grade silica adsorbent, stir and adsorb for 15 minutes, filter using 2000 mesh filter cloth, take the filtrate, and continue to use the same method as above to adsorb twice using new food grade silica adsorbent. If the sample test still has moisture, continue to adsorb until the adsorption test using silica adsorbent containing cobalt dichloride does not change color (moisture content ≤2.0 wt%). After adsorption is complete, the adsorbent is washed twice with purified water at 60°C (adsorbent and water weight ratio 1:1), filtered, and the washing liquid is collected and concentrated to (R)-3-hydroxybutyric acid content of 40.0-45.0 wt% (for the next adsorption). The washed adsorbent is dried at 105°C to constant weight and can be reused subsequently.

[0053] (3) The filtrate is concentrated under vacuum at 40°C and -0.1 mPa using a rotary evaporator to obtain (R)-3-hydroxybutyric acid solid crude product without overflow, and ethanol is recovered by condensation, about 30 g. Then, vacuum dry for 8 h to obtain 33.5 g of (R)-3-hydroxybutyric acid solid.

[0054] Example 2

[0055] A method for preparing (R)-3-hydroxybutyric acid solid based on adsorbent, comprising the following steps:

[0056] (1) Take 100 g of (R)-3-hydroxybutyric acid solution, concentrate to a solute mass fraction of 50.0 wt%, add 53.3 g of food grade 95% ethanol, and dilute to a solute mass fraction of 30.0 wt%.

[0057] (2) Add 50 g of food grade silica adsorbent, stir for 15 minutes, and filter using 2000 mesh filter cloth. Repeat the adsorption for the filtrate once. If the sample test still has moisture, continue to adsorb. Use silica adsorbent containing cobalt dichloride to adsorb test until no color change. The adsorbent is cleaned and recovered, and then dried at 105°C to constant weight, and can be reused subsequently.

[0058] (3) Use a rotary evaporator to concentrate under vacuum at 40°C and -0.1 mPa until no distillate is obtained, to obtain a solid crude (R)-3-hydroxybutyric acid, and condense and recover ethanol, about 50 g. Then, vacuum dry for 8 h to obtain 37.1 g of solid (R)-3-hydroxybutyric acid.

[0059] (4) Collect the adsorption of step (2), and add purified water at 60°C for cleaning twice at a weight ratio of 1:1, filter, collect the cleaning liquid, and concentrate to a (R)-3-hydroxybutyric acid content of 40.0-45.0 wt% (for the next adsorption).

[0060] Example 3

[0061] A method for preparing a solid (R)-3-hydroxybutyric acid based on an adsorbent, comprising the following steps:

[0062] (1) Take 100 g of (R)-3-hydroxybutyric acid solution, concentrate to a solute mass fraction of 50.0 wt%, add 120 g of food grade 95% ethanol, and dilute to a solute mass fraction of 20.0 wt%.

[0063] (2) Add 50 g of food grade silica adsorbent, stir for 15 minutes, and filter using 2000 mesh filter cloth. Repeat the adsorption for the filtrate once. If the sample test still has moisture, continue to adsorb. Use silica adsorbent containing cobalt dichloride to adsorb test until no color change. The adsorbent is cleaned and recovered, and then dried at 105°C to constant weight, and can be reused subsequently.

[0064] (3) Use a rotary evaporator to concentrate under vacuum at 40°C and -0.1 mPa until no distillate is obtained, to obtain a solid crude (R)-3-hydroxybutyric acid, and condense and recover ethanol, about 114 g. Then, vacuum dry for 8 h to obtain 36.8 g of solid (R)-3-hydroxybutyric acid.

[0065] (4) Collect the adsorption of step (16), and add purified water at 60°C for cleaning twice at a weight ratio of 1:1, filter, collect the cleaning liquid, and concentrate to a (R)-3-hydroxybutyric acid content of 40.0-45.0 wt% (for the next adsorption).

[0066] Example 4

[0067] A method for preparing a solid of (R)-3-hydroxybutyric acid based on an adsorbent, comprising the following steps:

[0068] (1) Take 100 g of a solution of (R)-3-hydroxybutyric acid, concentrate to a solute mass fraction of 50.0 wt%, add 120 g of recycled ethanol, and dilute to a solute mass fraction of 20.0 wt%.

[0069] (2) Add 50 g of recycled silica adsorbent, stir for 15 minutes, and filter using 2000 mesh filter cloth. Repeat the adsorption once for the filtrate. If the sample test still has moisture, continue to adsorb. Use silica adsorbent containing cobalt dichloride for adsorption test until no color change. The adsorbent is cleaned and recovered, and then dried at 105°C to constant weight for subsequent reuse.

[0070] (3) Use a rotary evaporator to vacuum concentrate at 40°C and -0.1 mPa without overflow to obtain a crude solid of (R)-3-hydroxybutyric acid, and condense and recover ethanol, about 112 g. Then, vacuum dry for 8 h to obtain 37.2 g of (R)-3-hydroxybutyric acid solid.

[0071] (4) Collect the adsorption of step (22), and add purified water at 60°C for cleaning 2 times according to a weight ratio of 1:1, filter, collect the cleaning liquid, and concentrate to a (R)-3-hydroxybutyric acid content of 40.0-45.0 wt% (for the next adsorption).

[0072] Comparative Example 1

[0073] A method for preparing a solid of (R)-3-hydroxybutyric acid based on an adsorbent, comprising the following steps:

[0074] (1) Take 100 g of a solution of (R)-3-hydroxybutyric acid, add 30 g of food-grade 95% ethanol, and dilute to a solute mass fraction of 10.0 wt%.

[0075] (2) Add 50 g of food-grade silica adsorbent, stir for 15 minutes, and filter using 2000 mesh filter cloth. Repeat the adsorption twice for the filtrate. If the sample test still has moisture, continue to adsorb. Use silica adsorbent containing cobalt dichloride for adsorption test until no color change. The total adsorption is repeated 4 times. The adsorbent is cleaned and recovered, and then dried at 105°C to constant weight for subsequent reuse.

[0076] (3) Use a rotary evaporator to vacuum concentrate at 40°C and -0.1 mPa without overflow to obtain a crude solid of (R)-3-hydroxybutyric acid, and condense and recover ethanol, about 26 g. Then, vacuum dry for 8 h to obtain 20.5 g of (R)-3-hydroxybutyric acid solid.

[0077] (4) Collect the adsorption of step (2) and wash twice with purified water at 60 °C at a weight ratio of 1 : 1, filter, collect the washings and concentrate to a (R)-3-hydroxybutyric acid content of 40.0-45.0 wt% (for the next adsorption).

[0078] Comparative Example 2

[0079] A method for preparing a (R)-3-hydroxybutyric acid solid based on an adsorbent, comprising the following steps:

[0080] (1) Take 100 g of a (R)-3-hydroxybutyric acid solution, concentrate to a solute mass fraction of 50 wt%, add 20 g of food-grade 95% ethanol, and dilute to a solute mass fraction of 40.0 wt%.

[0081] (2) Add 50 g of food-grade silica adsorbent, stir for 15 minutes, and filter using 2000 mesh filter cloth. Continue to repeat the adsorption of the filtrate twice. If the sample test still has moisture, continue to adsorb. Use silica adsorbent containing cobalt dichloride for adsorption test until no color change. A total of 4 times of repeated adsorption. The adsorbent is washed and recovered, and then dried at 105 °C until the weight is constant, and can be reused subsequently.

[0082] (3) Use a rotary evaporator to concentrate under vacuum at 40 °C and -0.1 mPa without overflow to obtain a (R)-3-hydroxybutyric acid solid crude product, and condense and recover ethanol, about 17 g. Then, vacuum dry for 8 h to obtain 21.6 g of (R)-3-hydroxybutyric acid solid.

[0083] (4) Collect the adsorption of step (2) and wash twice with purified water at 60 °C at a weight ratio of 1 : 1, filter, collect the washings and concentrate to a (R)-3-hydroxybutyric acid content of 40.0-45.0 wt% (for the next adsorption).

[0084] Comparative Example 3

[0085] A method for preparing a (R)-3-hydroxybutyric acid solid based on an adsorbent, comprising the following steps:

[0086] (1) Take 100 g of a (R)-3-hydroxybutyric acid solution and place it in a 500 mL beaker.

[0087] (2) Add 50 g of food-grade silica adsorbent, stir for 15 minutes, and filter using 2000 mesh filter cloth. Continue to repeat the adsorption of the filtrate 4 times. If the sample test still has moisture, continue to adsorb. Use silica adsorbent containing cobalt dichloride for adsorption test until no color change.

[0088] (3) Using a rotary evaporator, vacuum concentration was carried out at 40℃, -0.1 mPa, without dripping, and drying was continued for 8h, but no solid was precipitated, and the sample was still in a liquid state. Then, the drying temperature was increased to 60℃, and after drying for 2h, no water was evaporated, and no solid was precipitated, and the sample was a viscous liquid.

[0089] Product effect test

[0090] The optical purity and content of (R)-3-hydroxybutyric acid prepared in each of the above examples and comparative examples were detected, and the detection results are shown in Table 1.

[0091] Table 1 Optical purity and content (mass fraction) of (R)-3-hydroxybutyric acid of each example and comparative example

[0092]

[0093] From the above table, it can be seen that the optical purity of the product (R)-3-hydroxybutyric acid solid prepared in Examples 1-4 reaches 95.04-95.14%, the mass fraction reaches 97.06-98.05wt%, the yield reaches 82.1-90.8%, and no 3-hydroxybutyric acid ester oligomer is detected.

[0094] Compared with Example 1, the yield of (R)-3-hydroxybutyric acid solid in Comparative Example 1 decreased significantly, mainly because too much ethanol was used, the concentration of (R)-3-hydroxybutyric acid after dilution was too low, the adsorption efficiency of the adsorbent was lower, and the number of adsorption times needed to be increased, which caused the loss of (R)-3-hydroxybutyric acid in this process.

[0095] Compared with Example 1, the yield of (R)-3-hydroxybutyric acid solid in Comparative Example 2 decreased significantly, mainly because the amount of ethanol used was too small, the concentration of (R)-3-hydroxybutyric acid after dilution was too high, and (R)-3-hydroxybutyric acid could not be combined with water molecules well, resulting in too many adsorption times, which caused the loss of (R)-3-hydroxybutyric acid in this process.

[0096] Compared with Example 1, although Comparative Example 3 used an adsorbent to adsorb and dehydrate to no discoloration was detected by the adsorbent, but because no ethanol was added for dilution, solid (R)-3-hydroxybutyric acid could not be obtained subsequently, and the possible reason was that part of the water and (R)-3-hydroxybutyric acid had been combined by hydrogen bond, and the adsorbent could not adsorb the water completely, resulting in that even after vacuum drying, the water content could not be reduced well, and solid (R)-3-hydroxybutyric acid could not be obtained.

Claims

1. A process for the preparation of a solid of (R)-3-hydroxybutyric acid based on an adsorbent, characterized in that, The method comprises the following steps: (1) taking (R)-3-hydroxybutyric acid solution, adding ethanol to dilute to a solute mass fraction of 15%-35% to obtain a diluted solution; (2) using an adsorbent to adsorb and dehydrate the diluted solution, and then removing the adsorbent to obtain a dehydrated solution; (3) drying the dehydrated solution to obtain (R)-3-hydroxybutyric acid solid.

2. The production method according to claim 1, characterized by, In step (1), the solute mass fraction of the (R)-3-hydroxybutyric acid solution is 40-55wt%.

3. The production method according to claim 2, characterized by, In step (1), the (R)-3-hydroxybutyric acid solution is first heated and concentrated at 45-55℃ to a solute mass fraction of 40-55wt%.

4. The method of claim 1, wherein, In step (1), ethanol is added to dilute to a solute mass fraction of 20%-30%.

5. The preparation method according to claim 1, characterized in that, In step (1), the volume fraction of the ethanol is 90-99%.

6. The method of claim 1, wherein, In step (2), the adsorbent is a silica adsorbent.

7. The preparation method according to claim 1, characterized in that, In step (3), the drying is vacuum drying.

8. The method of claim 7, wherein, In step (3), the pressure of the vacuum drying is -0.09--0.1mPa, and / or the temperature of the vacuum drying is 35-45℃, and / or the time of the vacuum drying is 5-10h.

9. The method of claim 1, wherein, In step (3), after the drying, ethanol is condensed and recovered.

10. Use of the adsorption-based (R)-3-hydroxybutyric acid solid preparation method of claims 1-9 in the preparation of (R)-3-hydroxybutyric acid-containing solid food.

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