Refining method of high-purity acetone for biological medicine

Abstract

The invention provides a refining method of high-purity acetone for biological medicine, and relates to the field of acetone refining. The refining method of the high-purity acetone for the biological medicine comprises the following steps: raw material pretreatment, primary rectification, secondary rectification, drying and water removal, and multistage membrane separation. According to the refining method of the high-purity acetone for the biological medicine, impurities in industrial-grade acetone (the purity is 99.5 wt%) can be effectively removed through a simple and efficient refining treatment process, the high-purity and low-impurity-content high-purity acetone for the biological medicine is prepared, and the high-purity acetone for the biological medicine can be effectively applied to the fields of electronics, medicine, analysis and the like with high requirements on acetone.

Description

Technical Field

[0001] The present invention relates to the field of acetone refining, and particularly to a method for refining high-purity acetone for biopharmaceuticals. Background Art

[0002] Acetone, as a key organic compound, has a wide range of applications in many fields. There is a carbonyl functional group in the molecular structure of acetone, and this structure endows it with good solubility, enabling it to dissolve a variety of substances; for example, in the chemical industry, it can be used to dissolve materials with different properties such as plastics, rubbers, fibers, and oils, so as to meet subsequent processing, blending, and other requirements. In addition, the high reactivity brought by the carbonyl group in acetone allows acetone to participate in a variety of organic reactions, including addition, condensation, oxidation, and other reactions. In the pharmaceutical field, acetone is widely used in the extraction and synthesis processes of drugs. Many drug components have good solubility in acetone, and acetone can be used to extract active ingredients from natural plants or animal tissues. In the field of drug synthesis, on the one hand, acetone can be used as a reaction solvent to help the reactants mix and dissolve, promoting the progress of the reaction; on the other hand, acetone can be used as a drug intermediate to construct the molecular structure of drugs. For example, when synthesizing certain antibiotics, vitamins, hormones, and other drugs, acetone can participate in the reaction as a starting material or intermediate product, and can also synthesize piperazine drugs and antifungal drugs, etc. When acetone is used as a solvent or reaction medium, it will come into direct contact with drugs, and may even be ingested by patients or directly contacted, so it is necessary to ensure the high purity of acetone and that it does not contain impurities harmful to the human body, such as heavy metals, organic solvents, and other components, to ensure the health and safety of patients.

[0003] However, due to different production processes of acetone, the impurities contained in industrial-grade acetone products are also different. Among them, the main impurities in industrial-grade acetone are water, alcohol substances (such as methanol, ethanol), ketone substances (such as methyl ethyl ketone), and heavy metals, etc. At present, the water content in industrial-grade acetone products is relatively high, and due to the low boiling point of acetone, it is difficult to effectively remove impurities through ordinary distillation, and the impurity content in the prepared high-purity acetone cannot meet the requirements of high-end fields such as electronics, pharmaceuticals, and analysis. The existing methods for refining high-purity acetone mainly include sub-boiling distillation method, oxidation treatment method, isocyanate purification method, etc., but their treatment processes are complex, the treatment efficiency is low, the production energy consumption is high, the comprehensive production cost is high, and there may be potential hazards to the environment and products due to the residue of the purification agent in the refining process.

[0004] Therefore, providing a method for refining high-purity acetone for biopharmaceuticals with high purity and low impurity content has important technical significance and research value. Summary of the Invention

[0005] To solve the technical problems existing in the prior art, the present invention provides a method for refining high-purity acetone for biopharmaceuticals, which can effectively remove impurities in industrial-grade acetone (purity 99.5 wt%) through a simple and efficient refining process, and obtain high-purity acetone for biopharmaceuticals with low impurity content, which can be effectively applied to fields with high requirements for acetone such as electronics, medicine, and analysis.

[0006] To solve the above technical problems, the technical solutions adopted by the present invention are as follows: A method for refining high-purity acetone for biopharmaceuticals, which consists of the following steps: raw material pretreatment, primary distillation, secondary distillation, drying and water removal, and multi-stage membrane separation.

[0007] The method of the raw material pretreatment is to preheat industrial-grade acetone to 50-55°C to obtain the preheated acetone raw material, and continuously feed it into the primary distillation column; The method of the primary distillation is that the primary distillation column continuously receives the preheated acetone raw material, controls the temperature of the material in the kettle of the primary distillation column to be 60-65°C, and the temperature at the top of the column to be 55-56°C, and continuously performs atmospheric distillation; the top condensate of the primary distillation column is taken out as the primary distillation product and continuously fed into the secondary distillation column; The method of the secondary distillation is that the secondary distillation column continuously receives the primary distillation product, controls the temperature of the material in the kettle of the secondary distillation column to be 60-65°C, and the temperature at the top of the column to be 43-48°C, and continuously performs vacuum distillation; the top condensate of the secondary distillation column is taken out as the secondary distillation product; The secondary distillation product is dried and water-removed to obtain dried acetone; then it is subjected to multi-stage membrane separation to obtain high-purity acetone for biopharmaceuticals.

[0008] Preferably, in the raw material pretreatment, the preheating rate of industrial-grade acetone is 5-10°C / min; The feeding rate of the preheated acetone raw material into the primary distillation column is 10-12 L / h.

[0009] Preferably, in the primary distillation, the reflux ratio of the top condensate of the primary distillation is controlled to be 2-4:1.

[0010] Preferably, in the secondary distillation, the feeding rate of the primary distillation product into the secondary distillation column is 6-7 L / h; The vacuum distillation is carried out under the condition of an absolute pressure of 50-80 KPa; The reflux ratio of the top condensate of the secondary distillation is controlled to be 3-4:1.

[0011] Further, the method for drying and water removal is as follows: at a feeding rate of 5 - 10 L / min, the secondary rectification product passes through a drying tower filled with anhydrous magnesium sulfate, anhydrous potassium sulfate, and anhydrous potassium carbonate, and the residence time of the secondary rectification product in the drying tower is controlled to be 10 - 15 min to obtain dried acetone; The weight ratio of the anhydrous magnesium sulfate, anhydrous potassium sulfate, and anhydrous potassium carbonate is 2.5 - 3:1.5 - 2:0.5 - 1.

[0012] Further, the method for multi - stage membrane separation is as follows: at a feeding rate of 4 - 7 L / min, the dried acetone is subjected to primary membrane separation through a modified polyvinylidene fluoride membrane, and then subjected to secondary membrane separation through a polyvinylidene fluoride membrane with a pore size of 0.1 - 0.12 μm to obtain high - purity acetone for biopharmaceuticals; In the primary membrane separation, the temperature of the primary membrane separation is controlled to be 22 - 25°C, and the pressure of the primary membrane separation is 0.05 - 0.1 MPa; in the secondary membrane separation, the temperature of the secondary membrane separation is controlled to be 22 - 25°C, and the pressure of the secondary membrane separation is 0.05 - 0.1 MPa.

[0013] Further, the preparation method of the modified polyvinylidene fluoride membrane consists of the following steps: surface pretreatment and composite modification; The method for surface pretreatment is as follows: completely immerse a polyvinylidene fluoride membrane with a pore size of 0.2 - 0.22 μm into a sodium hydroxide solution, heat it to 50 - 55°C, keep it immersed for heat preservation, then take it out and wash it until neutral, and dry it to obtain a pre - modified polyvinylidene fluoride membrane; completely immerse the pre - modified polyvinylidene fluoride membrane into a pretreatment solution, immerse it at room temperature, then take it out and completely immerse it into absolute ethanol, let it stand, then take it out and dry it to obtain a surface - pretreated polyvinylidene fluoride membrane.

[0014] Preferably, in the surface pretreatment, the concentration of the sodium hydroxide solution is 3 - 3.5 mol / L; The volume ratio of the pre - modified polyvinylidene fluoride membrane to the pretreatment solution is 1:3 - 4; The pretreatment solution is prepared by putting tetraethyl orthosilicate into an ethanol solution with a weight 8 - 8.3 times that of tetraethyl orthosilicate, mixing evenly, adjusting the pH to 3.5 - 4, and stirring at room temperature.

[0015] Further, the method for composite modification is as follows: put ferric nitrate nonahydrate into deionized water and disperse it evenly to obtain a first liquid; completely immerse the surface - pretreated polyvinylidene fluoride membrane into the first liquid, immerse it at room temperature, then put a second liquid into the first liquid, react at room temperature under visible - light illumination, then take it out and rinse, and completely immerse it into an ammonium fluoride solution, immerse it at room temperature, then take it out and dry it to obtain a modified polyvinylidene fluoride membrane; The second liquid is an ethanol solution of trimesic acid and cumene hydroperoxide.

[0016] Preferably, in the composite modification, the volume ratio of the surface-pretreated polyvinylidene fluoride membrane to the first liquid is 1:3-4; The mass concentration of ferric nitrate nonahydrate in the first liquid is 14.5-15 wt%; In the second liquid, the mass concentration of trimesic acid is 7-7.3 wt%, the mass concentration of cumene hydroperoxide is 0.08-0.1 wt%, and the volume concentration of the ethanol solution is 50-55%; The molar ratio of ferric nitrate nonahydrate in the first liquid to trimesic acid in the second liquid is 1:0.85-0.9; The concentration of the ammonium fluoride solution is 20-25 mmol / L.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The refining method of high-purity acetone for biopharmaceuticals of the present invention preheats industrial-grade acetone. By increasing the raw material temperature to make it close to the operating temperature in the distillation column of the first rectification, heat consumption is reduced and rectification efficiency is improved; the preheated acetone raw material is fed into the first rectification column for atmospheric rectification. In the first rectification column, the concentration of the low-boiling acetone component in the vapor phase gradually increases, and the high-boiling impurities are enriched in the liquid phase, realizing the first separation of acetone and high-boiling impurities to obtain the first rectification product; then the first rectification product is fed into the second rectification column for vacuum rectification to further improve the purity of the product at the top of the column and obtain the second rectification product; the second rectification product is dried to remove water and subjected to multi-stage membrane separation to obtain high-purity acetone for biopharmaceuticals; it can effectively remove impurities in industrial-grade acetone (purity 99.5 wt%) through a simple and efficient refining process, and prepare high-purity acetone for biopharmaceuticals with low impurity content, which can be effectively applied to fields with high requirements for acetone such as electronics, medicine, and analysis.

[0018] (2) In the high-purity acetone for biopharmaceuticals finally prepared by the refining method of the present invention, the acetone content exceeds 99.998 wt%, the water content is 9-13 ppm, the contents of impurity ketones and alcohols are 69-76 ppb, the content of single metal cations is 90-96 ppt, and the acidity (calculated as acetic acid) is 2 ppm.

[0019] (3) The refining method of high-purity acetone for biopharmaceuticals of the present invention has a simple process method, is easy to control during the refining process, and the continuous and stable operation time exceeds 6 months. Specific Embodiments

[0020] In order to have a clearer understanding of the technical features, objectives, and effects of the present invention, the specific embodiments of the present invention are now described.

[0021] For a clearer understanding of the technical features, objectives, and effects of the present invention, the specific embodiments of the present invention will now be described. It should be noted that the following detailed descriptions are all exemplary and are intended to provide further explanations of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present invention belongs.

[0022] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present invention. As used herein, "first", "second", etc. are used to distinguish similar objects and are not used to describe a specific order or sequence. In addition, it should also be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0023] An embodiment of the present invention provides a method for refining high-purity acetone for biopharmaceuticals, which consists of the following steps: raw material pretreatment, primary rectification, secondary rectification, drying and water removal, and multi-stage membrane separation.

[0024] In the raw material pretreatment, before the industrial-grade acetone undergoes primary rectification, it needs to be preheated to increase the raw material temperature, making it close to the operating temperature in the rectification column of the primary rectification, reducing heat consumption, and improving the rectification efficiency. The specific operation is as follows: The industrial-grade acetone is transported to the preheater through a pipeline. The preheater uses a shell-and-tube heat exchanger, with the tube side for the industrial-grade acetone and the shell side for the heat transfer medium, thermal oil. The temperature of the thermal oil is controlled at 60 - 70°C; open the thermal oil valve of the preheater, control the heating rate at 5 - 10°C / min, preheat the industrial-grade acetone to 50 - 55°C. After the preheating is completed, the preheated acetone raw material is obtained; then open the transfer valve between the preheater and the primary rectification column, and control the preheated acetone raw material to be continuously fed into the primary rectification column at a feeding rate of 10 - 12 L / h through a feeding pump for primary rectification.

[0025] In the raw material pretreatment, the acetone content in the industrial-grade acetone is ≥99.5 wt%, the water content is ≤0.3 wt%, the contents of impurity ketones and alcohols are ≤0.1 wt%, and the acidity (calculated as acetic acid) is ≤0.002 wt%.

[0026] For the primary rectification, with a feed rate of 10 - 12 L / h, the preheated acetone raw material is continuously fed into the middle of the primary rectification column through a feed pump; ensure uniform feed distribution so that acetone can fully contact the rising steam and falling liquid in the column; control the temperature of the material in the kettle of the primary rectification column to be 60 - 65 °C and the temperature at the top of the column to be 55 - 56 °C, and continuously carry out atmospheric rectification; collect the steam phase at the top of the primary rectification column (mainly acetone containing low-boiling impurities), and after introducing it into the top condenser to be condensed into a liquid, control the reflux ratio to be 2 - 4:1. Part of the condensate is refluxed into the primary rectification column, and the other part is taken out as the primary rectification product and fed into the secondary rectification column for secondary rectification.

[0027] In the primary rectification, the primary rectification column used is a packed rectification column, and the packing used is wire mesh packing; during the primary rectification process, the rising steam phase in the primary rectification column contacts the falling liquid phase on the surface of the packing in a countercurrent manner, and a mass transfer and heat transfer process occurs; the concentration of the low-boiling acetone component in the steam phase in the primary rectification column gradually increases, while the high-boiling impurities are enriched in the liquid phase, realizing the first separation of acetone and high-boiling impurities.

[0028] After the primary rectification, the acetone content in the obtained primary rectification product is ≥99.65 wt%, the water content is ≤0.25 wt%, and the contents of impurity ketones and alcohols are ≤0.08 wt%.

[0029] For the secondary rectification, with a feed rate of 6 - 7 L / h, the primary rectification product is continuously fed into the middle of the secondary rectification column after being pressurized by a transfer pump; control the temperature of the material in the kettle of the secondary rectification column to be 60 - 65 °C and the temperature at the top of the column to be 43 - 48 °C, and continuously carry out secondary rectification under the condition of a pressure of 50 - 80 KPa (absolute pressure); by reducing the pressure, the boiling point of acetone is reduced, reducing the influence of high temperature on the quality of acetone; collect the steam phase at the top of the secondary rectification column, and after introducing it into the top condenser to be condensed into a liquid, control the reflux ratio to be 3 - 4:1. Part of the condensate is refluxed into the primary rectification column, and the other part is taken out as the secondary rectification product; the bottom liquid of the secondary rectification column is high-boiling impurities, which are discharged regularly and properly treated.

[0030] In the secondary rectification, the secondary rectification column used is a packed rectification column, and the packing used is wire mesh packing; during the secondary rectification process, the remaining low-boiling impurities and high-boiling impurities such as alcohols and ketones in the primary rectification product are removed in this step, and at the same time, a very small amount of acidic impurities can be further removed through the adsorption and separation of the packing in the rectification column, further improving the purity of the products at the top and bottom of the column.

[0031] After the secondary rectification, the acetone content in the obtained secondary rectification product is ≥99.75 wt%, the water content is ≤0.15 wt%, and the contents of impurity ketones and alcohols are ≤0.05 wt%.

[0032] For the drying and water removal, with a feeding rate of 5 - 10 L / min, the secondary rectification product passes through a drying tower filled with anhydrous magnesium sulfate, anhydrous potassium sulfate, and anhydrous potassium carbonate, and the residence time of the secondary rectification product in the drying tower is controlled to be 10 - 15 min to remove trace moisture in the secondary rectification product, obtaining dried acetone (with a moisture content ≤ 0.01 wt%).

[0033] In the drying and water removal, the weight ratio of anhydrous magnesium sulfate, anhydrous potassium sulfate, and anhydrous potassium carbonate is 2.5 - 3:1.5 - 2:0.5 - 1, and it is replaced every 4 - 5 months.

[0034] For the multi - stage membrane separation, with a feeding rate of 4 - 7 L / min, the dried acetone is slowly transported by a delivery pump into a primary membrane separation device equipped with a modified polyvinylidene fluoride (PVDF) membrane. The temperature of the primary membrane separation is controlled at 22 - 25°C, and the pressure of the primary membrane separation is 0.05 - 0.1 MPa. After continuous primary membrane separation, it is continuously fed into a secondary membrane separation device equipped with a common polyvinylidene fluoride (PVDF) membrane with a pore size of 0.1 - 0.12 μm. The temperature of the secondary membrane separation is controlled at 22 - 25°C, and the pressure of the secondary membrane separation is 0.05 - 0.1 MPa. After continuous secondary membrane separation, high - purity acetone for biopharmaceuticals is continuously obtained.

[0035] In the multi - stage membrane separation, the modified polyvinylidene fluoride membrane specifically adsorbs trace moisture, ketone impurities, alcohol impurities, heavy metals, etc. in the dried acetone, and at the same time, a polyvinylidene fluoride membrane with a pore size of 0.1 - 0.12 μm is used for secondary membrane separation to produce high - purity acetone for biopharmaceuticals.

[0036] In the high - purity acetone for biopharmaceuticals, the acetone content ≥ 99.99 wt%, the moisture content ≤ 13 ppm, the impurity ketone and alcohol content ≤ 77 ppb, the single metal cation content ≤ 96 ppt, and the acidity (calculated as acetic acid) ≤ 2 ppm.

[0037] In the multi - stage membrane separation, the preparation method of the modified polyvinylidene fluoride (PVDF) membrane consists of the following steps: surface pretreatment, composite modification.

[0038] For the surface pretreatment, a polyvinylidene fluoride (PVDF) membrane with a pore size of 0.2 - 0.22 μm is completely immersed in a sodium hydroxide solution (concentration 3 - 3.5 mol / L) with a volume 2 - 3 times that of the membrane. The temperature is raised to 50 - 55°C, and after soaking for 4 - 5 h with heat preservation, the PVDF membrane is taken out, washed with deionized water until neutral, and dried to obtain a pre-modified PVDF membrane. The pre-modified PVDF membrane is completely immersed in a pretreatment solution with a volume 3 - 4 times that of the membrane. After soaking at room temperature for 10 - 20 min, the PVDF membrane is taken out and completely immersed in absolute ethanol with a volume 5 - 6 times that of the membrane. After standing for 2 - 3 h, the PVDF membrane is taken out and dried to obtain a surface-pretreated PVDF membrane.

[0039] In the surface pretreatment, the pretreatment solution is prepared by adding tetraethyl orthosilicate to an ethanol solution (volume concentration 80 - 85%) with a weight 8 - 8.3 times that of tetraethyl orthosilicate, mixing evenly, and then adjusting the pH to 3.5 - 4 with hydrochloric acid at a concentration of 0.1 - 0.2 mol / L, followed by stirring at room temperature for 10 - 12 h.

[0040] For the composite modification, ferric nitrate nonahydrate is added to deionized water and stirred until dissolved to obtain a first liquid. Then, the surface-pretreated PVDF membrane is immersed in the first liquid with a volume 3 - 4 times that of the membrane. After soaking at room temperature for 20 - 30 min, a second liquid is added to the first liquid. Under visible light illumination conditions, after reacting at room temperature for 10 - 12 h, the PVDF membrane is taken out, rinsed successively with DMF and absolute ethanol, and then completely immersed in an ammonium fluoride solution (concentration 20 - 25 mmol / L) with a volume 2 - 3 times that of the membrane. After soaking at room temperature for 8 - 10 h, the PVDF membrane is taken out and dried to obtain a modified PVDF membrane.

[0041] In the composite modification, the mass concentration of ferric nitrate nonahydrate in the first liquid is 14.5 - 15 wt%.

[0042] The second liquid is prepared by dispersing trimesic acid and cumene hydroperoxide in an ethanol solution (volume concentration 50 - 55%) evenly. The mass concentration of trimesic acid in the second liquid is 7 - 7.3 wt%, and the mass concentration of cumene hydroperoxide in the second liquid is 0.08 - 0.1 wt%.

[0043] The molar ratio of ferric nitrate nonahydrate in the first liquid to trimesic acid in the second liquid is 1:0.85 - 0.9.

[0044] The following further illustrates the present invention in conjunction with some specific embodiments.

[0045] Example 1 This embodiment provides a method for refining high-purity acetone for biopharmaceuticals. The starting material, industrial-grade acetone, has an acetone content of 99.51 wt%, a water content of 0.29 wt%, an impurity ketone and alcohol content of 0.10 wt%, and an acidity (calculated as acetic acid) of 0.002 wt%.

[0046] The specific operation steps are as follows: 1. Raw material pretreatment Industrial-grade acetone is transported through a pipeline to a preheater. The preheater uses a shell-and-tube heat exchanger, with the tube side for industrial-grade acetone and the shell side for the heat transfer medium, thermal oil. The temperature of the thermal oil is controlled at 60°C. Open the thermal oil valve of the preheater, control the heating rate at 5°C / min, preheat the industrial-grade acetone to 50°C. After preheating, the preheated acetone raw material is obtained. Then open the transfer valve between the preheater and the primary distillation column, and control the preheated acetone raw material to be continuously fed into the primary distillation column at a feeding rate of 10 L / h through a feed pump for primary distillation.

[0047] 2. Primary distillation At a feeding rate of 10 L / h, the preheated acetone raw material is continuously fed into the middle of the primary distillation column through a feed pump. Control the temperature of the material in the kettle of the primary distillation column at 60°C and the temperature at the top of the column at 55°C, and continuously carry out atmospheric distillation. Collect the vapor phase at the top of the primary distillation column and introduce it into the top condenser to be condensed into a liquid. Then control the reflux ratio at 2:1. Part of the condensate is refluxed into the primary distillation column, and the other part is taken out as the primary distillation product and fed into the secondary distillation column for secondary distillation.

[0048] Among them, the primary distillation column used is a packed distillation column, and the packing used is wire mesh packing.

[0049] After detection, the acetone content in the primary distillation product is 99.67 wt%, the water content is 0.24 wt%, and the impurity ketone and alcohol content is 0.07 wt%.

[0050] 3. Secondary distillation At a feeding rate of 6 L / h, the primary distillation product is continuously fed into the middle of the secondary distillation column after being pressurized by a transfer pump. Control the temperature of the material in the kettle of the secondary distillation column at 60°C and the temperature at the top of the column at 43°C, and continuously carry out secondary distillation under the condition of a pressure of 50 KPa (absolute pressure). Collect the vapor phase at the top of the secondary distillation column and introduce it into the top condenser to be condensed into a liquid. Then control the reflux ratio at 3:1. Part of the condensate is refluxed into the secondary distillation column, and the other part is taken out as the secondary distillation product. The bottom liquid of the secondary distillation column is high-boiling impurities, which are discharged regularly and properly treated.

[0051] Among them, the secondary distillation column used is a packed distillation column, and the packing used is wire mesh packing; After detection, the acetone content in the secondary rectification product is 99.79 wt%, the water content is 0.14 wt%, and the contents of impurity ketones and alcohols are 0.05 wt%.

[0052] 4. Drying for water removal At a feeding rate of 5 L / min, the secondary rectification product passes through a drying tower filled with anhydrous magnesium sulfate, anhydrous potassium sulfate, and anhydrous potassium carbonate. The residence time of the secondary rectification product in the drying tower is controlled to be 15 min, and dried acetone (with a water content of 0.009 wt%) is obtained.

[0053] Among them, the weight ratio of anhydrous magnesium sulfate, anhydrous potassium sulfate, and anhydrous potassium carbonate is 2.5:1.5:0.5, and they are replaced every 4 - 5 months.

[0054] 5. Multi - stage membrane separation At a feeding rate of 4 L / min, the dried acetone is slowly transported by a transfer pump into a primary membrane separation device equipped with a modified polyvinylidene fluoride (PVDF) membrane. The temperature of the primary membrane separation is controlled at 22°C, and the pressure of the primary membrane separation is 0.05 MPa. After continuous primary membrane separation, it is continuously fed into a secondary membrane separation device equipped with a common polyvinylidene fluoride (PVDF) membrane with a pore size of 0.1 μm. The temperature of the secondary membrane separation is controlled at 22°C, and the pressure of the secondary membrane separation is 0.05 MPa. After continuous secondary membrane separation, high - purity acetone for biopharmaceuticals is continuously obtained.

[0055] After detection, in the high - purity acetone for biopharmaceuticals, the acetone content exceeds 99.998 wt%, the water content is 13 ppm, the contents of impurity ketones and alcohols are 76 ppb, the content of single metal cations is 96 ppt, and the acidity (calculated as acetic acid) is 2 ppm. Further, the refining method of the high - purity acetone for biopharmaceuticals in this example has a continuous and stable operation time of more than 6 months.

[0056] Among them, the preparation method of the modified polyvinylidene fluoride (PVDF) membrane consists of the following steps: surface pretreatment, composite modification.

[0057] (1) Surface pretreatment Completely immerse a polyvinylidene fluoride (PVDF) membrane with a pore size of 0.2 μm into 2 - fold volume of sodium hydroxide solution (concentration 3 mol / L), heat it to 50°C, keep it immersed for 4 h, then take out the polyvinylidene fluoride membrane, wash it with deionized water until neutral, and dry it to obtain a pre - modified polyvinylidene fluoride membrane; completely immerse the pre - modified polyvinylidene fluoride membrane into 3 - fold volume of a pretreatment solution, immerse it at room temperature for 10 min, then take out the polyvinylidene fluoride membrane and completely immerse it into 5 - fold volume of absolute ethanol, let it stand for 2 h, then take out the polyvinylidene fluoride membrane and dry it to obtain a surface - pretreated polyvinylidene fluoride membrane.

[0058] Among them, the pretreatment liquid is prepared by putting tetraethyl orthosilicate into an ethanol solution (volume concentration of 80%) with a weight 8 times that of tetraethyl orthosilicate, mixing evenly, and then adjusting the pH to 3.5 with hydrochloric acid with a concentration of 0.1 mol / L, and stirring at room temperature for 10 h.

[0059] (2) Composite modification Put ferric nitrate nonahydrate into deionized water, stir and dissolve to obtain the first liquid; then immerse the surface-pretreated polyvinylidene fluoride membrane into 3 times the volume of the first liquid, immerse at room temperature for 20 min, then put the second liquid into the first liquid, under visible light illumination conditions, react at room temperature for 10 h, take out the polyvinylidene fluoride membrane, rinse it successively with DMF and absolute ethanol, and then completely immerse it into 2 times the volume of ammonium fluoride solution (concentration 20 mmol / L), immerse at room temperature for 8 h, take out the polyvinylidene fluoride membrane, and dry it to obtain the modified polyvinylidene fluoride (PVDF) membrane.

[0060] Among them, the mass concentration of ferric nitrate nonahydrate in the first liquid is 14.5 wt%.

[0061] The second liquid is prepared by dispersing trimesic acid and cumene hydroperoxide into an ethanol solution (volume concentration 50%) evenly; the mass concentration of trimesic acid in the second liquid is 7 wt%, and the mass concentration of cumene hydroperoxide is 0.08 wt%.

[0062] The molar ratio of ferric nitrate nonahydrate in the first liquid to trimesic acid in the second liquid is 1:0.85.

[0063] Example 2 This example provides a refining method for high-purity acetone for biopharmaceuticals. The starting material, industrial-grade acetone, contains 99.51 wt% acetone, 0.29 wt% water, 0.10 wt% impurity ketones and alcohols, and the acidity (calculated as acetic acid) is 0.002 wt%.

[0064] The specific operation steps are as follows: 1. Raw material pretreatment Industrial-grade acetone is transported to the preheater through a pipeline. The preheater uses a shell-and-tube heat exchanger, with the tube side for industrial-grade acetone and the shell side for heat transfer medium thermal oil. The temperature of the heat transfer medium thermal oil is controlled at 65 °C; open the heat transfer medium valve of the preheater, control the heating rate at 8 °C / min, preheat the industrial-grade acetone to 52 °C, and after the preheating is completed, obtain the preheated acetone raw material; then open the transfer valve between the preheater and the primary distillation column, and control the preheated acetone raw material to be continuously fed into the primary distillation column at a feeding rate of 11 L / h through a feed pump for primary distillation.

[0065] 2. Primary distillation At a feed rate of 11 L / h, the preheated acetone raw material is continuously fed into the middle of the primary distillation column by a feed pump; the temperature of the material in the kettle of the primary distillation column is controlled at 62 °C, and the temperature at the top of the column is 55.5 °C. Atmospheric distillation is carried out continuously; the vapor phase at the top of the primary distillation column is collected and introduced into the top condenser to be condensed into a liquid. Then, the reflux ratio is controlled at 3:1. Part of the condensate is refluxed into the primary distillation column, and the other part is taken out as the primary distillation product and fed into the secondary distillation column for secondary distillation.

[0066] Among them, the primary distillation column used is a packed distillation column, and the packing used is wire mesh packing.

[0067] After detection, the acetone content in the primary distillation product is 99.71 wt%, the water content is 0.21 wt%, and the contents of impurity ketones and alcohols are 0.06 wt%.

[0068] 3. Secondary distillation At a feed rate of 6.5 L / h, the primary distillation product is continuously fed into the middle of the secondary distillation column after being pressurized by a transfer pump; the temperature of the material in the kettle of the secondary distillation column is controlled at 62 °C, and the temperature at the top of the column is 45 °C. Secondary distillation is carried out continuously under the condition of a pressure of 70 KPa (absolute pressure); the vapor phase at the top of the secondary distillation column is collected and introduced into the top condenser to be condensed into a liquid. Then, the reflux ratio is controlled at 3.2:1. Part of the condensate is refluxed into the primary distillation column, and the other part is taken out as the secondary distillation product; the bottom liquid of the secondary distillation column is high-boiling impurities, which are discharged regularly and properly treated.

[0069] Among them, the secondary distillation column used is a packed distillation column, and the packing used is wire mesh packing; After detection, the acetone content in the secondary distillation product is 99.82 wt%, the water content is 0.12 wt%, and the contents of impurity ketones and alcohols are 0.05 wt%.

[0070] 4. Drying and water removal At a feed rate of 8 L / min, the secondary distillation product passes through a drying tower filled with anhydrous magnesium sulfate, anhydrous potassium sulfate, and anhydrous potassium carbonate. The residence time of the secondary distillation product in the drying tower is controlled at 12 min to obtain dried acetone (water content is 0.008 wt%).

[0071] Among them, the weight ratio of anhydrous magnesium sulfate, anhydrous potassium sulfate, and anhydrous potassium carbonate is 2.8:1.7:0.8, and they are replaced every 4 - 5 months.

[0072] 5. Multi-stage membrane separation At a feeding rate of 6 L / min, the dried acetone is slowly transported by a transfer pump into a primary membrane separation device equipped with a modified polyvinylidene fluoride (PVDF) membrane. The temperature of the primary membrane separation is controlled at 24 °C, and the pressure of the primary membrane separation is 0.08 MPa. After continuous primary membrane separation, it is continuously fed into a secondary membrane separation device equipped with a common polyvinylidene fluoride (PVDF) membrane with a pore size of 0.1 μm. The temperature of the secondary membrane separation is controlled at 24 °C, and the pressure of the secondary membrane separation is 0.08 MPa. After continuous secondary membrane separation, high-purity acetone for biopharmaceuticals is continuously obtained.

[0073] After detection, in the high-purity acetone for biopharmaceuticals, the acetone content exceeds 99.998 wt%, the water content is 9 ppm, the contents of impurity ketones and alcohols are 69 ppb, the content of single metal cations is 90 ppt, and the acidity (calculated as acetic acid) is 2 ppm. Further, the refining method of the high-purity acetone for biopharmaceuticals in this example has a continuous and stable operation time of more than 6 months.

[0074] Among them, the preparation method of the modified polyvinylidene fluoride (PVDF) membrane consists of the following steps: surface pretreatment and composite modification.

[0075] (1) Surface pretreatment The polyvinylidene fluoride (PVDF) membrane with a pore size of 0.2 μm is completely immersed in a sodium hydroxide solution (concentration 3.2 mol / L) with a volume 2.5 times that of the membrane. The temperature is raised to 52 °C, and after holding for 4.5 h, the polyvinylidene fluoride membrane is taken out, washed with deionized water until neutral, and dried to obtain a pre-modified polyvinylidene fluoride membrane; the pre-modified polyvinylidene fluoride membrane is completely immersed in a pretreatment solution with a volume 3.5 times that of the membrane. After immersion at room temperature for 15 min, the polyvinylidene fluoride membrane is taken out and completely immersed in absolute ethanol with a volume 5.5 times that of the membrane. After standing for 2.5 h, the polyvinylidene fluoride membrane is taken out and dried to obtain a surface-pretreated polyvinylidene fluoride membrane.

[0076] Among them, the pretreatment solution is prepared by putting tetraethyl orthosilicate into an ethanol solution (volume concentration 83%) with a weight 8.2 times that of tetraethyl orthosilicate, mixing evenly, and then adjusting the pH to 3.7 with hydrochloric acid with a concentration of 0.15 mol / L and stirring at room temperature for 11 h.

[0077] (2) Composite modification Iron(III) nitrate nonahydrate was added to deionized water and stirred until dissolved to obtain a first liquid. Then, the surface-pretreated polyvinylidene fluoride membrane was immersed in 3.5 times the volume of the first liquid. After immersion at room temperature for 25 min, a second liquid was added to the first liquid. Under visible light illumination conditions, after reacting at room temperature for 11 h, the polyvinylidene fluoride membrane was taken out, rinsed successively with DMF and absolute ethanol, and then completely immersed in 2.5 volumes of ammonium fluoride solution (concentration 22 mmol / L). After immersion at room temperature for 9 h, the polyvinylidene fluoride membrane was taken out and dried to obtain a modified polyvinylidene fluoride (PVDF) membrane.

[0078] Among them, the mass concentration of iron(III) nitrate nonahydrate in the first liquid was 14.8 wt%.

[0079] The second liquid was prepared by uniformly dispersing trimesic acid and cumene hydroperoxide in an ethanol solution (volume concentration 52%); the mass concentration of trimesic acid in the second liquid was 7.2 wt%, and the mass concentration of cumene hydroperoxide was 0.09 wt%.

[0080] The molar ratio of iron(III) nitrate nonahydrate in the first liquid to trimesic acid in the second liquid was 1:0.87.

[0081] Example 3 This example provides a method for refining high-purity acetone for biomedical use. The starting material, industrial-grade acetone, contained 99.51 wt% acetone, 0.29 wt% water, 0.10 wt% impurity ketones and alcohols, and 0.002 wt% acidity (calculated as acetic acid).

[0082] The specific operation steps are as follows: 1. Raw material pretreatment Industrial-grade acetone was transported through a pipeline to a preheater. The preheater used a shell-and-tube heat exchanger, with the tube side for industrial-grade acetone and the shell side for heat transfer medium thermal oil. The temperature of the heat transfer medium thermal oil was controlled at 70 °C; the heat medium valve of the preheater was opened, and the heating rate was controlled at 10 °C / min to preheat the industrial-grade acetone to 55 °C. After preheating, the preheated acetone raw material was obtained; then, the transfer valve between the preheater and the primary distillation column was opened, and the preheated acetone raw material was continuously fed into the primary distillation column at a feed rate of 12 L / h through a feed pump for primary distillation.

[0083] 2. Primary distillation At a feed rate of 12 L / h, the preheated acetone raw material is continuously fed into the middle of the primary distillation column by a feed pump; the temperature of the material in the kettle of the primary distillation column is controlled at 65 °C, and the temperature at the top of the column is 56 °C, and atmospheric distillation is continuously carried out; the vapor phase at the top of the primary distillation column is collected and introduced into the top condenser to be condensed into a liquid, and then the reflux ratio is controlled at 4:1. Part of the condensate is refluxed into the primary distillation column, and the other part is taken out as the primary distillation product and fed into the secondary distillation column for secondary distillation.

[0084] Among them, the primary distillation column used is a packed distillation column, and the packing used is wire mesh packing.

[0085] After detection, the acetone content in the primary distillation product is 99.69 wt%, the water content is 0.23 wt%, and the contents of impurity ketones and alcohols are 0.06 wt%.

[0086] 3. Secondary distillation At a feed rate of 7 L / h, the primary distillation product is continuously fed into the middle of the secondary distillation column after being pressurized by a transfer pump; the temperature of the material in the kettle of the secondary distillation column is controlled at 65 °C, and the temperature at the top of the column is 48 °C, and secondary distillation is continuously carried out under the condition of a pressure of 80 KPa (absolute pressure); the vapor phase at the top of the secondary distillation column is collected and introduced into the top condenser to be condensed into a liquid, and then the reflux ratio is controlled at 4:1. Part of the condensate is refluxed into the primary distillation column, and the other part is taken out as the secondary distillation product; the bottom liquid of the secondary distillation column is high-boiling impurities, which are discharged regularly and properly treated.

[0087] Among them, the secondary distillation column used is a packed distillation column, and the packing used is wire mesh packing; After detection, the acetone content in the secondary distillation product is 99.81 wt%, the water content is 0.13 wt%, and the contents of impurity ketones and alcohols are 0.05 wt%.

[0088] 4. Drying and water removal At a feed rate of 10 L / min, the secondary distillation product passes through a drying tower filled with anhydrous magnesium sulfate, anhydrous potassium sulfate, and anhydrous potassium carbonate, and the residence time of the secondary distillation product in the drying tower is controlled at 10 min to obtain dried acetone (water content is 0.008 wt%).

[0089] Among them, the weight ratio of anhydrous magnesium sulfate, anhydrous potassium sulfate, and anhydrous potassium carbonate is 3:2:1, and they are replaced every 4 - 5 months.

[0090] 5. Multi-stage membrane separation At a feed rate of 7 L / min, the dried acetone is slowly transported by a transfer pump into a primary membrane separation device equipped with a modified polyvinylidene fluoride (PVDF) membrane. The temperature of the primary membrane separation is controlled at 25 °C and the pressure is 0.1 MPa. After continuous primary membrane separation, it is continuously fed into a secondary membrane separation device equipped with a common polyvinylidene fluoride (PVDF) membrane with a pore size of 0.1 μm. The temperature of the secondary membrane separation is controlled at 25 °C and the pressure is 0.1 MPa. After continuous secondary membrane separation, high-purity acetone for biopharmaceuticals is continuously obtained.

[0091] After testing, in the high-purity acetone for biopharmaceuticals, the acetone content exceeds 99.998 wt%, the water content is 10 ppm, the contents of impurity ketones and alcohols are 70 ppb, the content of single metal cations is 92 ppt, and the acidity (calculated as acetic acid) is 2 ppm. Further, the refining method of the high-purity acetone for biopharmaceuticals in this example has a continuous and stable operation time of more than 6 months.

[0092] Among them, the preparation method of the modified polyvinylidene fluoride (PVDF) membrane consists of the following steps: surface pretreatment and composite modification.

[0093] (1) Surface pretreatment The polyvinylidene fluoride (PVDF) membrane with a pore size of 0.2 μm is completely immersed in a sodium hydroxide solution (concentration 3.5 mol / L) with 3 times the volume, heated to 55 °C, and kept immersed for 5 h. Then, the polyvinylidene fluoride membrane is taken out, washed with deionized water until neutral, and dried to obtain a pre-modified polyvinylidene fluoride membrane. The pre-modified polyvinylidene fluoride membrane is completely immersed in a pretreatment solution with 4 times the volume. After immersing at room temperature for 20 min, the polyvinylidene fluoride membrane is taken out and completely immersed in anhydrous ethanol with 6 times the volume. After standing for 3 h, the polyvinylidene fluoride membrane is taken out and dried to obtain a surface-pretreated polyvinylidene fluoride membrane.

[0094] Among them, the pretreatment solution is prepared by putting tetraethyl orthosilicate into an ethanol solution (volume concentration 85%) with 8.3 times the weight, mixing evenly, and then adjusting the pH to 4 with hydrochloric acid with a concentration of 0.2 mol / L and stirring at room temperature for 12 h.

[0095] (2) Composite modification Ferric nitrate nonahydrate is put into deionized water and stirred to dissolve to obtain a first liquid. Then, the surface-pretreated polyvinylidene fluoride membrane is immersed in the first liquid with 4 times the volume. After immersing at room temperature for 30 min, a second liquid is added to the first liquid. Under visible light illumination conditions, after reacting at room temperature for 12 h, the polyvinylidene fluoride membrane is taken out, rinsed successively with DMF and anhydrous ethanol, and then completely immersed in a ammonium fluoride solution (concentration 25 mmol / L) with 3 volumes. After immersing at room temperature for 10 h, the polyvinylidene fluoride membrane is taken out and dried to prepare a modified polyvinylidene fluoride (PVDF) membrane.

[0096] Among them, the mass concentration of iron(III) nitrate nonahydrate in the first liquid is 15 wt%.

[0097] The second liquid is prepared by uniformly dispersing trimesic acid and cumene hydroperoxide into an ethanol solution (volume concentration 55%); the mass concentration of trimesic acid in the second liquid is 7.3 wt%, and the mass concentration of cumene hydroperoxide is 0.1 wt%.

[0098] The molar ratio of iron(III) nitrate nonahydrate in the first liquid to trimesic acid in the second liquid is 1:0.9.

[0099] It can be seen that for the purification method of high-purity acetone for biopharmaceuticals in Examples 1-3, the industrial-grade acetone is preheated. By increasing the raw material temperature to make it close to the operating temperature in the distillation column of the first distillation, heat consumption is reduced and the distillation efficiency is improved; the preheated acetone raw material is fed into the first distillation column for atmospheric distillation. The concentration of the low-boiling acetone component in the vapor phase in the first distillation column gradually increases, while the high-boiling impurities are enriched in the liquid phase, realizing the first separation of acetone and high-boiling impurities to obtain the first distillation product; then the first distillation product is fed into the second distillation column for vacuum distillation to further improve the purity of the product at the top of the column to obtain the second distillation product; after the second distillation product is dried in a drying column filled with a desiccant, it is subjected to primary membrane separation treatment using a modified polyvinylidene fluoride membrane and then secondary membrane separation treatment using a polyvinylidene fluoride membrane; among them, in the preparation of the modified polyvinylidene fluoride membrane used in the primary membrane separation treatment, in the surface pretreatment step, the polyvinylidene fluoride membrane is first surface-premodified with a sodium hydroxide solution, and then the premodified polyvinylidene fluoride membrane is put into a pretreatment solution (i.e., silica sol) to in-situ composite silica aerogel on the surface of the polyvinylidene fluoride membrane to obtain a surface-pretreated polyvinylidene fluoride membrane; then in the composite modification step, the surface-pretreated polyvinylidene fluoride membrane is impregnated into the first liquid, combined with the second liquid, and through the porous active sites of the silica aerogel, further composite iron-based metal-organic framework materials in an in-situ composite manner to obtain a modified polyvinylidene fluoride membrane. During the primary membrane separation process, through the coordination and adsorption of the silica aerogel and iron-based metal framework materials composite on the surface of the modified polyvinylidene fluoride membrane for impurities (such as heavy metals, ketone impurities, aldehyde impurities, moisture, etc.) in acetone, trace impurities in the dried acetone are specifically adsorbed, and at the same time, combined with the polyvinylidene fluoride membrane for secondary membrane separation, high-purity acetone for biopharmaceuticals is prepared.

[0100] Comparative Example 1 The technical solution of Example 2 is adopted, with the difference that in the preparation of the modified polyvinylidene fluoride (PVDF) membrane, the surface pretreatment step is omitted, and the polyvinylidene fluoride (PVDF) membrane with a pore size of 0.2 μm is directly used for the subsequent composite modification step.

[0101] For the acetone after drying in Comparative Example 1, after multi-stage membrane separation, the acetone content in the finally obtained acetone product is 99.989 wt%, the water content is 31 ppm, the contents of impurity ketones and alcohols are 195 ppb, the content of single metal cations is 207 ppt, and the acidity (calculated as acetic acid) is 5 ppm.

[0102] It can be seen that after omitting the surface pretreatment step in Comparative Example 1 and directly performing composite modification on the polyvinylidene fluoride membrane with the iron-based metal-organic framework material, its composite performance decreases; in the first-stage membrane separation treatment, the targeted separation performance for trace water, ketone impurities, aldehyde impurities, and heavy metal impurities in acetone decreases; specifically, the contents of various impurities in the finally obtained acetone product all increase to a certain extent.

[0103] Comparative Example 2 The technical solution of Example 2 is adopted, with the difference that in the preparation of the modified polyvinylidene fluoride (PVDF) membrane, the composite modification step is omitted, and the polyvinylidene fluoride membrane obtained in the surface pretreatment step is used in the first-stage membrane separation.

[0104] For the acetone after drying in Comparative Example 2, after multi-stage membrane separation, the acetone content in the finally obtained acetone product is 99.948 wt%, the water content is 71 ppm, the contents of impurity ketones and alcohols are 397 ppm, the content of single metal cations is 624 ppt, and the acidity (calculated as acetic acid) is 8 ppm.

[0105] It can be seen that after omitting the composite modification step in Comparative Example 2 and using only the polyvinylidene fluoride membrane surface-composited with silica aerogel for the first-stage membrane separation, it is impossible to perform targeted separation on trace water, ketone impurities, aldehyde impurities, and heavy metal impurities in acetone; specifically, the contents of various impurities in the finally obtained acetone product all increase significantly.

[0106] Unless otherwise specified, the percentages used in the present invention are all mass percentages.

[0107] Finally, it should be noted that the above are only the preferred embodiments of the present invention and are not used to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, for those skilled in the art, they can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements on some of the technical features. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for refining high-purity acetone for biomedicine, characterized in that: The process consists of the following steps: raw material pretreatment, primary distillation, secondary distillation, drying and water removal, and multi-stage membrane separation; The method for pretreating the raw material is to preheat industrial-grade acetone to 50-55° C., obtain the preheated acetone raw material, and continuously feed the preheated acetone raw material to a primary distillation tower; The primary distillation method is as follows: the primary distillation tower continuously receives the preheated acetone raw material, controls the material temperature in the kettle of the primary distillation tower to be 60-65° C., and the tower top temperature to be 55-56° C., and continuously performs atmospheric distillation; extracts the tower top condensate of the primary distillation tower as the primary distillation product, and continuously feeds it to the secondary distillation tower; The secondary distillation method comprises the following steps: the secondary distillation tower continuously receives the primary distillation product, controls the material temperature in the kettle of the secondary distillation tower to be 60-65° C., controls the tower top temperature to be 43-48° C., and continuously performs vacuum distillation; and extracts the tower top condensate of the secondary distillation tower as the secondary distillation product; The secondary distillation product is dried to remove water to obtain dried acetone; then it is separated by multi-stage membranes to obtain high-purity acetone for biomedicine.

2. The method for refining high-purity acetone for biomedicine according to claim 1, characterized in that: In the raw material pretreatment, the preheating rate of industrial grade acetone is 5-10°C / min; The feed rate of the preheated acetone raw material to the primary distillation tower is 10-12 L / h.

3. The method for refining high-purity acetone for biomedicine according to claim 1, characterized in that: In the primary distillation, the reflux ratio of the top condensate of the primary distillation is controlled to be 2-4:

1.

4. The method for refining high-purity acetone for biomedicine according to claim 1, characterized in that: In the secondary distillation, the feed rate of the primary distillation product to the secondary distillation tower is 6-7 L / h; Vacuum distillation is carried out under the condition of absolute pressure of 50-80KPa; The reflux ratio of the top condensate of the secondary distillation is controlled to be 3-4:

1.

5. The method for refining high-purity acetone for biomedicine according to claim 1, characterized in that: The drying and dehydration method comprises: passing the secondary distillation product through a drying tower filled with anhydrous magnesium sulfate, anhydrous potassium sulfate and anhydrous potassium carbonate at a feed rate of 5-10 L / min, controlling the residence time of the secondary distillation product in the drying tower to be 10-15 min, and obtaining dried acetone; The weight ratio of the anhydrous magnesium sulfate, anhydrous potassium sulfate and anhydrous potassium carbonate is 2.5-3:1.5-2:0.5-1.

6. The method for refining high-purity acetone for biomedicine according to claim 1, characterized in that: The multi-stage membrane separation method is as follows: at a feed rate of 4-7 L / min, the dried acetone is subjected to primary membrane separation through a modified polyvinylidene fluoride membrane, and then subjected to secondary membrane separation through a polyvinylidene fluoride membrane with a pore size of 0.1-0.12 μm, to obtain high-purity acetone for biomedicine; In the primary membrane separation, the primary membrane separation temperature is controlled at 22-25° C., and the primary membrane separation pressure is controlled at 0.05-0.1 MPa; in the secondary membrane separation, the secondary membrane separation temperature is controlled at 22-25° C., and the secondary membrane separation pressure is controlled at 0.05-0.1 MPa.

7. The method for refining high-purity acetone for biomedicine according to claim 1, characterized in that: The preparation method of the modified polyvinylidene fluoride film comprises the following steps: surface pretreatment and composite modification; The surface pretreatment method comprises the following steps: completely immersing a polyvinylidene fluoride membrane with a pore size of 0.2-0.22 μm in a sodium hydroxide solution, heating the membrane to 50-55° C., keeping the membrane warm, taking the membrane out and washing the membrane to neutrality, and drying the membrane to obtain a pre-modified polyvinylidene fluoride membrane; completely immersing the pre-modified polyvinylidene fluoride membrane in a pretreatment solution, immersing the membrane at room temperature, taking the membrane out and completely immersing the membrane in anhydrous ethanol, standing the membrane, taking the membrane out and drying the membrane to obtain a surface pre-treated polyvinylidene fluoride membrane.

8. The method for refining high-purity acetone for biomedicine according to claim 7, characterized in that: In the surface pretreatment, the concentration of the sodium hydroxide solution is 3-3.5 mol / L; The volume ratio of the pre-modified polyvinylidene fluoride membrane to the pre-treatment liquid is 1:3-4; The pretreatment liquid is prepared by adding tetraethyl orthosilicate into 8-8.3 times the weight of ethanol solution, mixing the mixture evenly, adjusting the pH to 3.5-4, and stirring the mixture at room temperature.

9. The method for refining high-purity acetone for biomedicine according to claim 7, characterized in that: The composite modification method comprises the following steps: adding ferric nitrate nonahydrate into deionized water and dispersing it uniformly to obtain a first liquid; completely immersing the surface pretreated polyvinylidene fluoride membrane into the first liquid, immersing it at room temperature, adding a second liquid into the first liquid, reacting it at room temperature under visible light illumination, taking it out and rinsing it, completely immersing it into an ammonium fluoride solution, immersing it at room temperature, taking it out and drying it, and obtaining a modified polyvinylidene fluoride membrane; The second liquid is an ethanol solution of trimesic acid and cumene hydroperoxide.

10. The method for refining high-purity acetone for biomedicine according to claim 9, characterized in that: In the composite modification, the volume ratio of the surface pretreated polyvinylidene fluoride membrane to the first liquid is 1:3-4; The mass concentration of ferric nitrate nonahydrate in the first liquid is 14.5-15wt%; In the second liquid, the mass concentration of trimesic acid is 7-7.3wt%, the mass concentration of cumene hydroperoxide is 0.08-0.1wt%, and the volume concentration of the ethanol solution is 50-55%; The molar ratio of the ferric nitrate nonahydrate in the first liquid to the trimesic acid in the second liquid is 1:0.85-0.9; The concentration of the ammonium fluoride solution is 20-25 mmol / L.