CN112778123A - 3-sodium hydroxybutyrate crystal form and preparation method and application thereof - Google Patents
3-sodium hydroxybutyrate crystal form and preparation method and application thereof Download PDFInfo
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- 239000013078 crystal Substances 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 93
- NBPUSGBJDWCHKC-UHFFFAOYSA-M sodium 3-hydroxybutyrate Chemical compound [Na+].CC(O)CC([O-])=O NBPUSGBJDWCHKC-UHFFFAOYSA-M 0.000 claims abstract description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000008367 deionised water Substances 0.000 claims abstract description 17
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 17
- 239000012043 crude product Substances 0.000 claims abstract description 16
- OMSUIQOIVADKIM-UHFFFAOYSA-N ethyl 3-hydroxybutyrate Chemical compound CCOC(=O)CC(C)O OMSUIQOIVADKIM-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000000758 substrate Substances 0.000 claims abstract description 16
- LDLDJEAVRNAEBW-UHFFFAOYSA-N Methyl 3-hydroxybutyrate Chemical compound COC(=O)CC(C)O LDLDJEAVRNAEBW-UHFFFAOYSA-N 0.000 claims abstract description 13
- OHQCTLBHQBPXLU-UHFFFAOYSA-N propan-2-yl 3-hydroxybutanoate Chemical compound CC(C)OC(=O)CC(C)O OHQCTLBHQBPXLU-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000001694 spray drying Methods 0.000 claims abstract description 6
- 238000000967 suction filtration Methods 0.000 claims abstract description 5
- 239000000243 solution Substances 0.000 claims description 39
- 238000002347 injection Methods 0.000 claims description 14
- 239000007924 injection Substances 0.000 claims description 14
- 239000000843 powder Substances 0.000 claims description 6
- 150000002576 ketones Chemical class 0.000 claims description 4
- 238000002441 X-ray diffraction Methods 0.000 claims description 3
- 230000005855 radiation Effects 0.000 claims description 2
- 229910002483 Cu Ka Inorganic materials 0.000 claims 1
- 238000011085 pressure filtration Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 13
- 239000000047 product Substances 0.000 abstract description 13
- 239000003960 organic solvent Substances 0.000 abstract description 11
- 238000002425 crystallisation Methods 0.000 abstract description 10
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- 238000010521 absorption reaction Methods 0.000 abstract description 3
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- 239000007921 spray Substances 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 159000000000 sodium salts Chemical class 0.000 description 7
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 6
- 238000002083 X-ray spectrum Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 4
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- 239000012295 chemical reaction liquid Substances 0.000 description 3
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- 208000024827 Alzheimer disease Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
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- OXUQOKIBNYSTGF-UHFFFAOYSA-L calcium;3-hydroxybutanoate Chemical compound [Ca+2].CC(O)CC([O-])=O.CC(O)CC([O-])=O OXUQOKIBNYSTGF-UHFFFAOYSA-L 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
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- 235000013305 food Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
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- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- ZIMQIJFHENOQDO-UHFFFAOYSA-L magnesium;3-hydroxybutanoate Chemical compound [Mg+2].CC(O)CC([O-])=O.CC(O)CC([O-])=O ZIMQIJFHENOQDO-UHFFFAOYSA-L 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/01—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention is applicable to the technical field of chemistry, and provides a sodium 3-hydroxybutyrate crystal form and a preparation method and application thereof, wherein the preparation method of the sodium 3-hydroxybutyrate crystal form comprises the following steps: dissolving a substrate in deionized water to obtain a substrate solution; wherein the substrate is at least one of methyl 3-hydroxybutyrate, ethyl 3-hydroxybutyrate and isopropyl 3-hydroxybutyrate; dissolving sodium hydroxide in deionized water to obtain a sodium hydroxide solution; adding a sodium hydroxide solution into a substrate solution for reaction, and then performing reduced pressure suction filtration treatment to remove methanol to obtain a crude product; and carrying out spray drying treatment on the crude product to obtain the crystal form of the sodium 3-hydroxybutyrate. The invention only adopts water as a reaction medium, does not need other organic solvents for recrystallization, realizes 2 processes of preparation and crystallization by one-step method, and the prepared sodium 3-hydroxybutyrate product has high crystallinity, stable crystal form and difficult moisture absorption and caking.
Description
Technical Field
The invention belongs to the technical field of chemistry, and particularly relates to a sodium 3-hydroxybutyrate crystal form and a preparation method and application thereof.
Background
Beta-hydroxybutyrate (BHB) is a natural metabolite formed during fat digestion and metabolism, called ketone body, and is an energy-intensive molecule that, as a dietary supplement ingredient, functions primarily to naturally provide energy to the brain, heart and muscles without the involvement of glucose and the intake of low carbohydrates. Sodium 3-hydroxybutyrate, a stable mineral sodium salt donor for BHB, is commonly used in combination with calcium 3-hydroxybutyrate and magnesium 3-hydroxybutyrate to form a dry powder which decomposes to free Beta-hydroxybutyrate and mineral ions for absorption by the human body after ingestion.
3-hydroxy butyric acid and its sodium salt can offer the energy source for most tissues of the body as the main ketone body, have very large application value and prospect in health care products, food and pharmaceutical industry, including: accelerating the weight loss; stimulating the expression of various health-promoting genes; reducing the incidence of inflammatory complications; the exercise performance and the training efficiency are improved; enhancing metabolic efficiency; providing optimal energy for the heart and reducing the incidence of cardiovascular diseases; increase insulin sensitivity; preventing cancer and related diseases caused by glucose metabolism disorder; zeng river cognitive ability, preventing senile dementia, prolonging life, etc.
At present, sodium 3-hydroxybutyrate is mainly prepared by a chemical method, ethyl 3-hydroxybutyrate is adopted as a raw material, and deionized water is adopted as a solvent; reacting ethyl 3-hydroxybutyrate with sodium hydroxide to form salt; then decolorizing with active carbon, and evaporating water to obtain the finished product of the 3-sodium hydroxybutyrate.
In the salification reaction process, only water is used as a solvent, recrystallization operation cannot be realized, and water is required to be evaporated to dryness for recrystallization, so that the steps are complicated, the obtained crystals are blocky, the crystals are required to be ground into powder, the time is spent, dust damage is easily caused, and the prepared product has no crystal form or low crystallinity, is extremely easy to absorb moisture and agglomerate, and is not beneficial to later-stage application or storage. In addition, the conventional process usually uses ethanol as a crystallization solvent, which generates a large amount of ethanol, and causes high additional cost and environmental damage during the recycling and discharging of water. In addition, products such as sodium 3-hydroxybutyrate and the like are mostly used for food additives and the like, and the requirement of organic solvent on solvent residue is strict, so that the process complexity is increased.
Disclosure of Invention
The embodiment of the invention aims to provide a preparation method of a crystal form of sodium 3-hydroxybutyrate, and aims to solve the problems in the background art.
The embodiment of the invention is realized in such a way that the preparation method of the crystal form of the sodium 3-hydroxybutyrate comprises the following steps:
dissolving a substrate in deionized water to obtain a substrate solution; wherein the substrate is at least one of methyl 3-hydroxybutyrate, ethyl 3-hydroxybutyrate and isopropyl 3-hydroxybutyrate;
dissolving sodium hydroxide in deionized water to obtain a sodium hydroxide solution;
adding a sodium hydroxide solution into a substrate solution for reaction, and then performing reduced pressure suction filtration treatment to remove methanol to obtain a crude product;
and carrying out spray drying treatment on the crude product to obtain the crystal form of the sodium 3-hydroxybutyrate.
In a preferable embodiment of the invention, the concentration of the substrate solution is 1-5 g/mL, and the concentration of the sodium hydroxide solution is 0.1-1 g/mL.
As another preferable scheme of the embodiment of the invention, the concentration of the substrate solution is 2-3 g/mL, and the concentration of the sodium hydroxide solution is 0.5-0.6 g/mL
Specifically, the amount of sodium hydroxide is directly related to the content of the final product, and in order to prevent the sodium hydroxide from being excessive, the methyl 3-hydroxybutyrate can be selectively slightly excessive during feeding.
In another preferable scheme of the embodiment of the invention, in the step, the reaction temperature is 5-25 ℃.
In another preferable scheme of the embodiment of the invention, in the step, the temperature of the reduced pressure suction filtration treatment is 45-55 ℃. Methanol is generated in the reaction process of the invention, and in order to ensure the safety of spraying, the methanol in the reaction system needs to be removed in the step.
As another preferable scheme of the embodiment of the invention, in the step, the inlet air temperature of the spray drying treatment is 120-200 ℃, the sample injection speed is 500-1000 mL/L, and the sample injection pressure is 0.2-0.4 Mpa.
Specifically, the spray drying process may be performed by a bench spray dryer with equipment model YC-500.
The embodiment of the invention also aims to provide a crystal form of sodium 3-hydroxybutyrate prepared by the preparation method.
As another preferable mode of the embodiment of the present invention, the crystal form of sodium 3-hydroxybutyrate has a distinct characteristic diffraction peak at least at 2 θ =6.1 ± 0.2 °, 7.1 ± 0.2 °, 11.4 ± 0.2 °, 11.9 ± 0.2 °, 17.3 ± 0.2 °, 18.7 ± 0.2 °, 20.1 ± 0.2 °, 20.5 ± 0.2 °, 22 ± 0.2 °, 22.3 ± 0.2 °, 23.0 ± 0.2 °, 26 ± 0.2 °, 27.5 ± 0.2 °, 29.3 ± 0.2 °, 29.9 ± 0.2 °, and 30.4 ± 0.2 ° in the 2 θ angle of the X-ray spectrum measured by using Cu — ka radiation.
Specifically, the X-ray spectrum can be tested by a german brueck D8 ADVANCE DAVINCI-ray diffractometer; specifically, a sample of the milled, homogenized sodium 3-hydroxybutyrate powder was laid flat on a ground glass sheet and then compacted with a glass sheet for testing. The instrument setting parameters are as follows: cu target, K α light source (wavelength λ = l.540596 a rays), scanning range 4-50 ° (10 °/min), tube current 30Ma, tube voltage (40 kV) measurement.
As another preferred scheme of the embodiment of the invention, the crystal form of the sodium 3-hydroxybutyrate is loose round spherical powder.
Another object of an embodiment of the present invention is to provide an application of the above crystal form of sodium 3-hydroxybutyrate in the preparation of ketone body donors.
According to the preparation method of the sodium 3-hydroxybutyrate crystal form provided by the embodiment of the invention, only water is used as a reaction medium, other organic solvents are not needed for recrystallization, 2 processes of preparation and crystallization are completed by a one-step method, all solvents can be recycled in the preparation process, the cost is reduced, the process operation is simple and environment-friendly, the product purity is over 99%, the product yield is over 95%, and the preparation method is suitable for amplification production. The sodium 3-hydroxybutyrate product prepared by the preparation method has high crystallinity, stable crystal form and difficult moisture absorption and agglomeration. In addition, although ethanol is produced in the above production method, the produced ethanol is distilled off and is clean.
Drawings
FIG. 1 is an X-ray diffraction pattern of sodium 3-hydroxybutyrate prepared as in example 1.
FIG. 2 is a graph showing the comparison of the X-ray diffraction between sodium 3-hydroxybutyrate prepared in example 1 and sodium 3-hydroxybutyrate obtained by crystallization from an organic solvent.
FIG. 3 is a SEM photograph of sodium 3-hydroxybutyrate prepared in example 1 compared with a conventional sodium 3-hydroxybutyrate prepared by crystallization from an organic solvent. In FIG. 3, a and b represent sodium 3-hydroxybutyrate prepared in example 1; c. d is sodium 3-hydroxybutyrate obtained by crystallization with an organic solvent.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
This example provides a method for preparing a sodium 3-hydroxybutyrate product comprising the steps of:
s1, dissolving 500g of methyl 3-hydroxybutyrate in 200mL of deionized water to obtain a methyl 3-hydroxybutyrate solution.
S2, dissolving 170g of sodium hydroxide in 300mL of deionized water, and naturally cooling to room temperature to obtain a sodium hydroxide solution.
S3, adding all the sodium hydroxide solution into the methyl 3-hydroxybutyrate solution for reaction, stirring at the speed of 400rpm for 3.5h, controlling the reaction temperature to be 20 ℃, after the GC detection reaction is finished, placing the reaction solution at the temperature of 50 ℃ for decompression and suction filtration treatment to remove methanol, and obtaining a crude product.
S4, the crude product is sprayed and dried by a market YC-500 desk spray dryer to obtain the sodium 3-hydroxybutyrate. Wherein the parameters of the spray dryer are set as follows: the air inlet temperature is 160 ℃, the sample injection speed is 800mL/L, and the sample injection pressure is 0.3 Mpa.
Example 2
This example provides a method for preparing a sodium 3-hydroxybutyrate product comprising the steps of:
s1, dissolving 400g of ethyl 3-hydroxybutyrate in 200mL of deionized water to obtain a solution of ethyl 3-hydroxybutyrate.
S2, dissolving 150g of sodium hydroxide in 300mL of deionized water, and naturally cooling to room temperature to obtain a sodium hydroxide solution.
S3, adding all the sodium hydroxide solution into the ethyl 3-hydroxybutyrate solution for reaction, stirring at the speed of 400rpm for 3 hours, controlling the reaction temperature to be 5 ℃, after GC detection reaction is finished, placing the reaction liquid at the temperature of 45 ℃ for vacuum filtration treatment to remove methanol, and obtaining a crude product.
S4, the crude product is sprayed and dried by a market YC-500 desk spray dryer to obtain the sodium 3-hydroxybutyrate. Wherein the parameters of the spray dryer are set as follows: the air inlet temperature is 120 ℃, the sample injection speed is 500mL/L, and the sample injection pressure is 0.2 Mpa.
Example 3
This example provides a method for preparing a sodium 3-hydroxybutyrate product comprising the steps of:
s1, 600g of isopropyl 3-hydroxybutyrate is dissolved in 200mL of deionized water to obtain a solution of isopropyl 3-hydroxybutyrate.
S2, dissolving 180g of sodium hydroxide in 300mL of deionized water, and naturally cooling to room temperature to obtain a sodium hydroxide solution.
S3, adding all the sodium hydroxide solution into the isopropyl 3-hydroxybutyrate solution for reaction, stirring at the speed of 400rpm for 4 hours, controlling the reaction temperature to be 25 ℃, after the GC detection reaction is finished, placing the reaction solution at the temperature of 55 ℃ for vacuum filtration treatment to remove methanol, and obtaining a crude product.
S4, the crude product is sprayed and dried by a market YC-500 desk spray dryer to obtain the sodium 3-hydroxybutyrate. Wherein the parameters of the spray dryer are set as follows: the air inlet temperature is 200 ℃, the sample injection speed is 1000mL/L, and the sample injection pressure is 0.4 Mpa.
Example 4
This example provides a method for preparing a sodium 3-hydroxybutyrate product comprising the steps of:
s1, dissolving 550g of methyl 3-hydroxybutyrate in 200mL of deionized water to obtain a methyl 3-hydroxybutyrate solution.
S2, 160g of sodium hydroxide is dissolved in 300mL of deionized water and naturally cooled to room temperature to obtain a sodium hydroxide solution.
S3, adding all the sodium hydroxide solution into the methyl 3-hydroxybutyrate solution for reaction, stirring at 300rpm for 3h, controlling the reaction temperature to be 10 ℃, after GC detection reaction is finished, placing the reaction liquid at 52 ℃ for vacuum filtration treatment to remove methanol, and obtaining a crude product.
S4, the crude product is sprayed and dried by a market YC-500 desk spray dryer to obtain the sodium 3-hydroxybutyrate. Wherein the parameters of the spray dryer are set as follows: the air inlet temperature is 150 ℃, the sample injection speed is 700mL/L, and the sample injection pressure is 0.3 Mpa.
Example 5
This example provides a method for preparing a sodium 3-hydroxybutyrate product comprising the steps of:
s1, 580g of methyl 3-hydroxybutyrate is dissolved in 200mL of deionized water to obtain a methyl 3-hydroxybutyrate solution.
S2, dissolving 165g of sodium hydroxide in 300mL of deionized water, and naturally cooling to room temperature to obtain a sodium hydroxide solution.
S3, adding all the sodium hydroxide solution into the methyl 3-hydroxybutyrate solution for reaction, stirring at 500rpm for 4h, controlling the reaction temperature to be 15 ℃, after GC detection reaction is finished, placing the reaction liquid at 50 ℃ for vacuum filtration treatment to remove methanol, and obtaining a crude product.
S4, the crude product is sprayed and dried by a market YC-500 desk spray dryer to obtain the sodium 3-hydroxybutyrate. Wherein the parameters of the spray dryer are set as follows: the air inlet temperature is 180 ℃, the sample injection speed is 800mL/L, and the sample injection pressure is 0.3 Mpa.
Experimental example:
firstly, respectively carrying out X-ray spectrum analysis on the sodium 3-hydroxybutyrate (marked as sodium salt for spraying) prepared in the example 1 and the sodium 3-hydroxybutyrate (marked as sodium salt for crystallization) obtained by crystallizing the sodium 3-hydroxybutyrate by using an organic solvent in the prior art by a German Bruker D8 ADVANCE DAVINCI-ray diffractometer; specifically, a sample of the milled, homogenized sodium 3-hydroxybutyrate powder was laid flat on a ground glass sheet and then compacted with a glass sheet for testing. The instrument setting parameters are as follows: cu target, K α light source (wavelength λ = l.540596 a rays), scanning range 4-50 ° (10 °/min), tube current 30Ma, tube voltage (40 kV) measurement.
An X-ray spectrum of the sodium 3-hydroxybutyrate (marked as spray sodium salt) prepared in example 1 is shown in figure 1, and the 2 theta angle of the sodium 3-hydroxybutyrate prepared in example 1 is 2 theta =6.1 degrees, 7.1 degrees, 11.4 degrees, 11.9 degrees, 17.3 degrees, 18.7 degrees, 20.1 degrees, 20.5 degrees, 22 degrees, 22.3 degrees, 23.0 degrees, 26 degrees, 27.5 degrees, 29.3 degrees, 29.9 degrees and 30.4 degrees, and has obvious characteristic diffraction peaks; an X-ray spectrum of sodium 3-hydroxybutyrate (marked as crystalline sodium salt) obtained by crystallizing with an organic solvent in the prior art is shown in figure 2, and the 2 theta angle of the sodium 3-hydroxybutyrate (marked as crystalline sodium salt) is 6.1 degrees, 7.1 degrees, 8.8 degrees, 9.6 degrees, 11.4 degrees, 14.3 degrees, 16.9 degrees, 18.3 degrees, 19.3 degrees, 20.1 degrees, 20.9 degrees, 23.0 degrees, 26.8 degrees, 27.8 degrees, 29.9 degrees, 33.8 degrees and 37.4 degrees, and obvious characteristic peaks appear. As can be seen from figures 1-2, the sodium 3-hydroxybutyrate prepared by the embodiment of the invention has higher diffraction peak intensity, better crystallization degree and more ordered growth of corresponding crystal faces.
Second, SEM analysis of the sodium 3-hydroxybutyrate prepared in example 1 and the sodium 3-hydroxybutyrate crystallized by an organic solvent according to the prior art is performed, and the analysis results are shown in FIG. 3, wherein in FIG. 3, a and b are the sodium 3-hydroxybutyrate prepared in example 1; c. d is sodium 3-hydroxybutyrate obtained by crystallization with an organic solvent. As can be seen from fig. 3, the single crystal of sodium 3-hydroxybutyrate obtained by crystallization with an organic solvent is in the shape of a strip, and a plurality of crystals are easily aggregated; the shape of the sodium 3-hydroxybutyrate prepared by the embodiment of the invention is spherical, and the particles are relatively uniformly dispersed.
Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.
Claims (10)
1. A preparation method of a sodium 3-hydroxybutyrate crystal form is characterized by comprising the following steps:
dissolving a substrate in deionized water to obtain a substrate solution; wherein the substrate is at least one of methyl 3-hydroxybutyrate, ethyl 3-hydroxybutyrate and isopropyl 3-hydroxybutyrate;
dissolving sodium hydroxide in deionized water to obtain a sodium hydroxide solution;
adding a sodium hydroxide solution into a substrate solution for reaction, and then performing reduced pressure suction filtration treatment to remove methanol to obtain a crude product;
and carrying out spray drying treatment on the crude product to obtain the crystal form of the sodium 3-hydroxybutyrate.
2. The preparation method of the sodium 3-hydroxybutyrate crystal form according to claim 1, wherein the concentration of the substrate solution is 1-5 g/mL, and the concentration of the sodium hydroxide solution is 0.1-1 g/mL.
3. The preparation method of the sodium 3-hydroxybutyrate crystal form according to claim 1, wherein the concentration of the substrate solution is 2-3 g/mL, and the concentration of the sodium hydroxide solution is 0.5-0.6 g/mL.
4. The preparation method of the sodium 3-hydroxybutyrate crystal form according to claim 1, wherein the reaction temperature in the step is 5-25 ℃.
5. The preparation method of the sodium 3-hydroxybutyrate crystal form according to claim 1, wherein the temperature of the reduced pressure filtration treatment is 45-55 ℃.
6. The preparation method of the sodium 3-hydroxybutyrate crystal form according to claim 1, wherein in the step, the air inlet temperature of spray drying treatment is 120-200 ℃, the sample injection speed is 500-1000 mL/L, and the sample injection pressure is 0.2-0.4 MPa.
7. A crystalline form of sodium 3-hydroxybutyrate prepared by the preparation method of any one of claims 1-6.
8. A crystalline form of sodium 3-hydroxybutyrate of claim 7 with an X-ray pattern having distinct characteristic diffraction peaks at least one of 2 θ =6.1 ± 0.2 °, 7.1 ± 0.2 °, 11.4 ± 0.2 °, 11.9 ± 0.2 °, 17.3 ± 0.2 °, 18.7 ± 0.2 °, 20.1 ± 0.2 °, 20.5 ± 0.2 °, 22 ± 0.2 °, 22.3 ± 0.2 °, 23.0 ± 0.2 °, 26 ± 0.2 °, 27.5 ± 0.2 °, 29.3 ± 0.2 °, 29.9 ± 0.2 °, 30.4 ± 0.2 ° using Cu-Ka radiation.
9. The crystalline form of sodium 3-hydroxybutyrate of claim 7 as a loosely spherical powder.
10. Use of the crystalline form of sodium 3-hydroxybutyrate of claim 7 or 8 or 9 in the preparation of a ketone body donor.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114573444A (en) * | 2022-03-19 | 2022-06-03 | 宁波酶赛生物工程有限公司 | Preparation process of 3-hydroxysuccinic acid sodium salt and potassium salt |
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| WO2025056246A1 (en) * | 2023-09-11 | 2025-03-20 | Societe Des Produits Nestle S.A. | Polymorphs and compositions comprising same |
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