Industrial production process of high-batch stability cross-linked povidone

Abstract

This invention discloses an industrial production process for crosslinked polyvinylpyrrolidone with high batch stability, belonging to the field of polymer material synthesis technology. The process first mixes N-vinylpyrrolidone monomer, comonomer, and an oil-soluble initiator, then mixes them with water, nanocellulose, and inorganic salts to form a Pickering suspension. Polymerization is then initiated by stepwise heating. In the second stage, a multifunctional crosslinking agent is dynamically added dropwise to construct a crosslinking network. A high-performance modifier is added in the later stages of polymerization for in-situ graft modification. After the reaction, the product is purified by shearing, centrifugation, and supercritical CO2 fluid extraction and drying to obtain the final product. This invention endows the product with multiple functions through dynamic crosslinking and in-situ modification, and utilizes supercritical CO2 extraction to replace organic solvent washing for green purification. The resulting product has excellent performance and no organic solvent residue. This process overcomes the system fluctuations and mass transfer bottlenecks encountered in the scale-up process of traditional suspension polymerization, exhibiting excellent process repeatability and making it particularly suitable for the large-scale industrial production of crosslinked polyvinylpyrrolidone.

Description

Technical Field

[0001] This invention relates to the field of polymer material synthesis technology, and mainly to an industrial production process, specifically an industrial production process for cross-linked polyvinylpyrrolidone with high batch stability. Background Technology

[0002] Crosslinked polyvinylpyrrolidone (PVPP), as an important crosslinked polymer, has traditionally been widely used in pharmaceutical disintegrants, food clarifying agents, and cosmetic stabilizers due to its excellent water absorption and swelling properties, network stability, and biocompatibility. In recent years, with the in-depth development of materials science, the application boundaries of PVPP are rapidly expanding, demonstrating enormous application potential in emerging fields such as high-end water treatment special adsorption, intelligent separation membranes, non-polar solvent system adsorption, and novel drug delivery systems. These emerging fields place higher demands on PVPP for diverse functions (such as environmental responsiveness, high adsorption capacity, and special surface properties).

[0003] Currently, commercially available crosslinked polyvinylpyrrolidone products are mainly prepared through traditional aqueous solution polymerization or reverse suspension polymerization. However, traditional processes have the following significant drawbacks in actual industrial production: First, poor batch stability is a chronic problem of traditional processes. Traditional processes often use surfactants such as polyvinyl alcohol (PVA) as suspending and dispersing agents, which are easily affected by shear force fluctuations and heating rates during polymerization, leading to droplet coalescence. This results in significant fluctuations in particle size distribution, crosslinking degree, and swelling properties between different batches of products, severely restricting the stability for high-end applications. Secondly, large amounts of organic solvents (toluene, cyclohexane) are often used as dispersion media or post-treatment detergents during polymerization, posing risks of environmental pollution and solvent residue, making it difficult to meet the requirements of green and clean production. Thirdly, traditional modification methods are mostly post-treatment grafting or physical blending, resulting in weak bonding between the modifier and the polymer matrix, easy detachment, and poor functional durability. Furthermore, the crosslinking agents used (such as N,N'-methylenebisacrylamide) have limited functions, forming a brittle network that is difficult to endow the product with special mechanical toughness or intelligent responsiveness. Finally, the entire traditional process is energy-intensive, cumbersome, and difficult to achieve precise control of product performance and high added value.

[0004] To address the aforementioned issues, there is an urgent need to develop a new industrial production process for cross-linked polyvinylpyrrolidone that combines high batch stability, adjustable functionality, and a completely green and environmentally friendly process. Summary of the Invention

[0005] To address the industry pain points of existing technologies, such as poor batch stability, limited functionality, easy detachment of modified cross-linked polyvinylpyrrolidone, and organic solvent residues in traditional post-processing, the present invention aims to provide a green industrial production process for cross-linked polyvinylpyrrolidone with high batch stability and functional modification.

[0006] This invention aims to solve the aforementioned problems through the following technical approaches: First, it employs nanocellulose to construct a Pickering suspension-stabilized system, utilizing its irreversible interfacial anchoring effect to overcome system fluctuations caused by the easy desorption of traditional dispersants, thereby improving the reproducibility and stability between batches in industrial production; second, it combines stepwise initiation with dynamic dropwise addition of multifunctional crosslinking agents to construct a crosslinking network with a designable structure and high toughness; third, it introduces a high-performance modifier in the middle stage of polymerization for in-situ chemical grafting, achieving efficient and robust functionalization of the product; fourth, it uses supercritical CO2 fluid extraction technology to replace traditional organic solvent washing, achieving green purification of the product and efficient protection of the microporous structure after removing inorganic salts and centrifuging dehydration, resulting in a final product free of organic solvent residue. Ultimately, a high-value-added crosslinked polyvinylpyrrolidone product with high batch stability, excellent performance, adjustable function, and purity and safety is obtained.

[0007] To achieve the above objectives, the present invention provides the following technical solution: This invention provides an industrial production process for cross-linked polyvinylpyrrolidone with high batch stability, comprising the following steps: S1. Preparation of pre-emulsion: N-vinylpyrrolidone monomer, functionalized comonomer and oil-soluble initiator are mixed and dissolved to obtain mixed monomer liquid; then the mixed monomer liquid, deionized water, dispersant and inorganic salt are mixed and stirred to form a uniform and stable micro-suspension; S2, Stepwise Initiation and Dynamic Crosslinking Polymerization: The micro-suspension system obtained in step S1 is heated to carry out the first initiation stage polymerization, and then the temperature is increased and a second initiator is added. At the same time, a specific multifunctional crosslinking agent is dynamically added to carry out the second initiation and crosslinking reaction. S3, In-situ grafting modification: When the reaction in step S2 reaches a specific stage, a high-performance modifier is added to the reaction system, and the reaction continues to achieve in-situ grafting modification; S4. Green Post-processing and Product Collection: After cooling the reaction system obtained in step S3, solid particles are obtained by high-speed shearing and centrifugation. Inorganic salts are removed by washing with deionized water, followed by centrifugation and dehydration again. The particles are then pre-vacuum dried to a moisture content of less than 5%. Subsequently, supercritical CO2 fluid extraction technology is used, with anhydrous ethanol as an entrainer, to purify the pre-dried wet solid particles. After drying, the particles are pulverized and sieved to obtain functionalized modified cross-linked polyvinylpyrrolidone powder.

[0008] Preferably: An industrial production process for cross-linked polyvinylpyrrolidone with high batch stability includes the following steps: S1. Preparation of Pre-emulsion: Mix 150-350g of N-vinylpyrrolidone monomer (NVP), 30-80g of functionalized comonomer (selected from one or more of N-vinylcaprolactam, methacrylic acid, or bio-based itaconic acid) with 0.5-1.2g of oil-soluble initiator azobisisobutyronitrile (AIBN) in a container. Stir at 200-400 rpm for 5-15 minutes at 20-30°C until the AIBN is completely dissolved to obtain a mixed monomer solution. Subsequently, add the above mixed monomer solution, 500-1200g of deionized water, 8-20g of dispersant nanocellulose (CNC), and 200-600g of inorganic salt (selected from sodium sulfate or sodium chloride) sequentially to a reactor equipped with a mechanical stirrer and temperature control device. Start stirring and continue mixing at 300-600 rpm for 15-25 minutes until the entire system forms a uniform, stable, milky white micro-suspension. This step utilizes the salting-out effect of inorganic salts and the picking stabilizing effect of nanocellulose to form oil / water suspension droplets with uniform particle size and stability, laying the foundation for subsequent heterogeneous polymerization.

[0009] S2. Stepwise Initiation and Dynamic Crosslinking Polymerization: The micro-suspension system obtained in step S1 is heated to 65-75°C at a rate of 1-3°C / min and maintained at this temperature for 40-80 minutes. During this stage, the AIBN dissolved and encapsulated inside the monomer droplets initiates the initial polymerization, forming primary polymer particles. Subsequently, the system temperature is raised to 78-82°C, and 0.8-2.0 g of the second initiator, benzoyl peroxide (BPO, which can be pre-dissolved in 5-15 mL of anhydrous ethanol to facilitate dispersion, is added to the system through the feed port. This trace amount of ethanol evaporates and condenses with the system during the subsequent heating and polymerization process, without interfering with the stability of the suspension polymerization system. Simultaneously with the addition of the second initiator, a specific multifunctional crosslinking agent is added dropwise to the reaction system at a constant rate of 0.8-1.5 g / min using a high-precision metering pump. This specific multifunctional crosslinking agent is selected from pentaerythritol triacrylate (PETA), divinyl adipate, or an L-cysteine ​​derivative containing disulfide bonds (SS), with a total addition amount of 15-40 g. The dropwise addition is synchronized with the reaction process and lasts for 60-100 minutes. This step, through stepwise temperature initiation and dynamic dropwise addition of the crosslinking agent, precisely introduces crosslinking points during polymer growth, forming a uniform and structurally designable crosslinked network, endowing the product with special mechanical properties or environmental responsiveness.

[0010] S3. In-situ grafting modification: 40-70 minutes after adding the second initiator in step S2, add 5-15g of pretreated high-performance modifier to the reaction system under continuous stirring at 450-550 rpm. The high-performance modifier is selected from fluorosilanes, hyperbranched polyamides, or polyhedral oligomeric silsesquioxanes (POSS). For fluorosilanes and POSS, the pretreatment method is as follows: mix them with anhydrous ethanol at a ratio of 1g:1mL, add glacial acetic acid to adjust the pH to 4-5, stir at room temperature for 10-20 minutes (the trace amount of anhydrous ethanol introduced during pretreatment acts as a co-solvent, which is easily volatilized at the subsequent reaction temperature, does not affect the stability of the aqueous suspension system, and is eventually completely removed by supercritical CO2 extraction), and then add it to the reaction system at a uniform rate over 1-3 minutes through a constant pressure dropping funnel; for hyperbranched polyamides, they can be added directly without pretreatment and added to the reaction system over 1-3 minutes. After adding the modifier, maintain the reaction temperature at 72-78℃ and continue stirring for 80-150 minutes. This step utilizes the large number of active free radicals present in the late stage of polymerization to enable the high-performance modifier to undergo chemical graft copolymerization with the polymer chain through its active groups, thereby achieving in-situ and efficient functionalization modification of the product and improving its surface properties, thermal stability, or adsorption performance.

[0011] S4. Green Post-processing and Product Collection: After the reaction is complete, the reaction system obtained in step S3 is naturally cooled to 20-30℃. The material in the reactor is transferred to a high-speed shear disperser and sheared at 5000-10000 rpm for 3-8 minutes to break up any possible gel agglomerates. The broken slurry is then transferred to a centrifuge and centrifuged at 3500-4500 rpm for 10-15 minutes to separate solid polymer particles. The solid particles are washed with deionized water to remove residual inorganic salts until the filtrate is free of halide or sulfate ions. The filtrate is then centrifuged again for dehydration. Subsequently, the dehydrated solid particles are pre-vacuum dried at 40-50℃ and a vacuum of 0.06-0.08 MPa for 1-2 hours to remove most of the free water inside the particles, reducing the moisture content to below 5%. The pre-dried wet solid particles were purified using a supercritical CO2 fluid extraction apparatus: the extraction vessel temperature was set at 32-34℃, the pressure at 8-10 MPa, the CO2 flow rate at 15-25 L / h, and anhydrous ethanol was used as the entrainer (flow rate of 5%-10% of the CO2 flow rate). The extraction time was 70-90 minutes. After extraction, the particles were transferred to a vacuum drying oven and dried at 45-55℃ and a vacuum of 0.06-0.08 MPa for 2-3 hours. Finally, the dried particles were pulverized using an air jet mill and passed through a 120-mesh standard sieve. The undersize material was collected to obtain a white to off-white functionalized modified cross-linked polyvinylpyrrolidone powder. This step first removes inorganic salts by washing with water, and then removes a large amount of free water through gentle pre-vacuum drying, avoiding the mass transfer resistance of supercritical fluid penetrating a strongly polar water film. Subsequently, supercritical CO2 fluid extraction was used to replace traditional washing with large amounts of organic solvents. A trace amount of anhydrous ethanol was introduced as a co-soluble entrainer, synergistically enhancing the effect with supercritical CO2 to deeply elute trace amounts of water, polar monomers (NVPs), initiators, and other small molecule impurities remaining deep within the particle pores. Simultaneously, because supercritical fluids do not undergo gas-liquid phase transitions and have virtually no surface tension during extraction and depressurization, they effectively prevent the collapse of the microporous structure caused by capillary forces within the particles during conventional high-temperature drying, thus protecting and endowing the product with a higher specific surface area and more porous and developed pores.

[0012] Preferably, in step S1, the amount of N-vinylpyrrolidone monomer is 260g, the amount of functionalized comonomer bio-based itaconic acid is 45g, the amount of oil-soluble initiator AIBN is 1.1g, the stirring and dissolving temperature is 26℃, the stirring speed is 380 rpm, and the stirring time is 14 minutes.

[0013] Preferably, in step S1, the amount of deionized water is 1100g, the amount of dispersant nanocellulose (CNC) is 18g, the amount of inorganic salt sodium chloride is 550g, the mixing speed is 550 rpm, and the mixing time is 24 minutes.

[0014] Preferably, in step S2, the heating rate of the first initiation stage is 2℃ / min, the reaction temperature is 74℃, and the reaction time is 65 minutes; the reaction temperature of the second initiation stage is 82℃, and the amount of the second initiator BPO is 1.8g, which is dissolved in 14mL of anhydrous ethanol beforehand.

[0015] Preferably, in step S2, the specific multifunctional crosslinking agent is divinyl adipate, the total amount added is 35g, the dropping rate is 1.4 g / min, and the dropping and reaction duration is 95 minutes.

[0016] Preferably, in step S3, the high-performance modifier is polyhedral oligomeric silsesquioxane (POSS), and the amount added is 14g. The pretreatment conditions are as follows: mix with 14mL of anhydrous ethanol, add glacial acetic acid to adjust the pH value to 4.3, stir at room temperature for 16 minutes; after adding the modifier, the reaction temperature is 77℃, and the reaction time is continued for 140 minutes.

[0017] Preferably, in step S4, the high-speed shear disperser operates at a speed of 8500 rpm and a processing time of 7 minutes; the centrifuge operates at a speed of 4300 rpm and a centrifugation time of 14 minutes.

[0018] Preferably, in step S4, the conditions for supercritical CO2 fluid extraction are: extraction vessel temperature 34℃, pressure 9.8MPa, CO2 flow rate 24L / hour, and extraction time 88 minutes; the conditions for vacuum drying are: temperature 54℃, vacuum degree 0.08MPa, and drying time 3 hours.

[0019] Preferably, the main pharmaceutical sources involved in this invention are as follows: N-vinylpyrrolidone (NVP) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; nanocellulose (CNC), N-vinylcaprolactam (NVCL), pentaerythritol triacrylate (PETA), and L-cysteine ​​derivatives containing disulfide bonds (SS) were purchased from Shanghai Maclean Biochemical Technology Co., Ltd.; divinyl adipate was purchased from Nanjing Kelang Technology Co., Ltd.; fluorinated silanes were purchased from Nanjing Nengde New Material Technology Co., Ltd.; polyhedral oligomeric silsesquioxanes (POSS) were purchased from Xi'an Qiyue Biotechnology Co., Ltd.; and hyperbranched polyamides were purchased from Wuhan Hyperbranched Resin Co., Ltd.

[0020] Advantages of this invention This invention uses nanocellulose (CNC) to construct a Pickering suspension stabilization system, which not only significantly improves the stability of the suspension and obtains polymer microspheres with more uniform particle size, but also makes the whole system more green and environmentally friendly, avoiding the biotoxicity and environmental burden that may be caused by synthetic dispersants.

[0021] This invention employs a process that combines stepwise initiation with dynamic dropwise addition of specific multifunctional crosslinking agents (such as PETA, divinyl adipate, and L-cysteine ​​derivatives containing SS bonds). This process can precisely and uniformly introduce crosslinking points during polymer chain growth, thereby constructing a crosslinking network with designable structure and controllable performance. This significantly improves the mechanical strength and swelling properties of the product or endows it with special functions such as redox responsiveness.

[0022] This invention introduces pretreated high-performance modifiers (such as fluorosilanes, hyperbranched polyamides, and POSS) during the later stages of the polymerization reaction, utilizing the abundant active free radicals in the system to achieve in-situ chemical grafting of the modifiers to the polymer chains. This method offers high modification efficiency and strong bonding, significantly improving the surface properties and thermal stability of the product or providing a large number of active adsorption sites, thus achieving efficient and stable functionalization of the product.

[0023] In the post-processing stage of this invention, water washing is used for desalination, followed by supercritical CO2 fluid extraction technology to replace the traditional large-scale washing step with organic solvents. This technology cleverly utilizes trace amounts of anhydrous ethanol as a co-solubilizing entrainer, which synergistically enhances the effect with the supercritical CO2 fluid, successfully breaking down the strong polar water film barrier within the pores of the pre-dried wet particles and forming a locally co-solubilized system. This not only significantly improves the fluid's penetration efficiency and deep elution effect on small molecule impurities such as residual polar monomers (NVPs) and initiators, but also simultaneously achieves the entrainment and removal of some water. Furthermore, because the supercritical fluid does not undergo a gas-liquid phase transition and has virtually no surface tension during extraction and depressurization, it effectively prevents the collapse of the microporous structure caused by capillary forces within the particles during conventional drying, thus protecting and endowing the product with a higher specific surface area and more porous and developed pores. The trace amounts of ethanol, acting as both an entrainer and co-solvent, are deeply removed during subsequent fluid depressurization and gentle vacuum drying, truly achieving zero organic solvent residue in the finished product. The entire process completely avoids the consumption of large amounts of harmful organic solvents, significantly reducing the overall energy consumption and environmental protection costs, which is in line with the development trend of green chemistry and clean production.

[0024] This invention utilizes a combination of technologies, including salting out, Pickering stabilization, dynamic crosslinking, in-situ modification, and green extraction, to form a complete, efficient, and environmentally friendly preparation process. This process offers high flexibility; by selecting different comonomers, crosslinking agents, and modifiers, a series of functional products with varying temperature sensitivity, pH responsiveness, adsorption capacity, mechanical strength, or surface properties can be easily customized, greatly expanding the application areas and market value of crosslinked povidone.

[0025] Furthermore, the process described in this invention has excellent potential for industrial scale-up, and is particularly suitable for large-scale production. Traditional suspension polymerization methods often suffer from uneven shear distribution and poor heat and mass transfer due to changes in reactor geometry during industrial scale-up, leading to severe batch-to-batch fluctuations. This invention fundamentally solves this problem through a combination of technologies: First, the Pickering suspension system constructed using nanocellulose exhibits irreversible interfacial anchoring effects, demonstrating strong tolerance to shear force fluctuations and localized turbulence common in large industrial reactors, ensuring droplet stability after scale-up; second, the stepwise initiation and dynamic addition of crosslinking agents effectively avoid instantaneous gelation and localized bursts of polymerization caused by traditional single-feeding, flattening the exothermic peak and significantly reducing the pressure on heat transfer and temperature control in large industrial reactors; finally, supercritical CO2 fluid extraction replaces traditional large-volume organic solvent washing, eliminating the environmental burden of industrial solvent recovery, and its mass transfer efficiency is not limited by reactor size, facilitating continuous or semi-continuous scale-up operations. In summary, this invention maintains extremely low batch-to-batch performance fluctuations (RSD<2%) during the process of scaling up from small-scale to industrial production, and has extremely high industrial implementation value. Attached Figure Description

[0026] Figure 1 This is a scanning electron microscope (SEM) image of the modified cross-linked polyvinyl ketone product prepared in Example 3 of the present invention.

[0027] Figure 2 This is a scanning electron microscope (SEM) image of the sample prepared in Comparative Example 1 of this invention.

[0028] Figure 3 This is a radar chart comparing the thermal decomposition temperature and water contact angle of the samples in Example 3 and Comparative Examples 4-5 of the present invention. Detailed Implementation

[0029] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that, unless otherwise specified, the following embodiments and features described therein can be combined with each other.

[0030] The following specific examples illustrate the implementation of the present invention. It should be noted that the following embodiments are mainly described based on small-scale laboratory tests, but the process design of the present invention is not limited thereto. Because the Pickering stabilization system used in this invention has high tolerance to shear field fluctuations, and both dynamic dropping and supercritical extraction are unit operations that are easily linearly scaled up, when this process is scaled up to industrial production scale (e.g., 1000L-5000L reactors), those skilled in the art only need to proportionally increase the feed rate and adjust the stirring speed according to the equipment diameter ratio to maintain a similar blade tip linear velocity, while simultaneously converting the supercritical CO2 flow rate proportionally to the material loading. This allows for the reproduction of high batch stability and product performance comparable to the embodiments of the present invention in large industrial reactors.

[0031] Example 1

[0032] S1. Preparation of Pre-emulsion: 180g of N-vinylpyrrolidone monomer, 40g of functionalized comonomer N-vinylcaprolactam, and 0.6g of oil-soluble initiator azobisisobutyronitrile (AIBN) are mixed in a clean container and stirred at 250 rpm for 8 minutes at 22°C until the AIBN is completely dissolved, obtaining a mixed monomer solution. Subsequently, the above mixed monomer solution, 600g of deionized water, 10g of dispersant nanocellulose (CNC), and 250g of inorganic salt sodium chloride are sequentially added to a reactor equipped with a mechanical stirrer and temperature control device. Stirring is started, and mixing is continued at 350 rpm for 18 minutes until the entire system forms a uniform, stable milky white micro-suspension.

[0033] S2. Stepwise Initiation and Dynamic Crosslinking Polymerization: The microsuspension system obtained in step S1 was heated to 68°C at a programmed heating rate of 1.5°C / min and maintained at this temperature for 50 minutes. Subsequently, the system temperature was raised to 79°C, and 1.0 g of the second initiator, benzoyl peroxide (BPO, pre-dissolved in 8 mL of anhydrous ethanol), was added to the system through the feed port. Simultaneously with the addition of the second initiator, 18 g of the specific multifunctional crosslinking agent, pentaerythritol triacrylate (PETA), was added dropwise to the reaction system at a constant rate of 0.9 g / min using a high-precision metering pump. The dropwise addition was synchronized with the reaction process and continued for 70 minutes.

[0034] S3. In-situ grafting modification: 45 minutes after adding the second initiator in step S2, under continuous stirring at 450 rpm, add 6 g of pretreated high-performance modifier polyhedral oligomeric silsesquioxane (POSS, pretreatment method: mix POSS with anhydrous ethanol at a ratio of 1 g: 1 mL, adjust the pH to 4.5 by adding glacial acetic acid dropwise, and stir at room temperature for 12 minutes). After adding the modifier, maintain the reaction temperature at 74℃ and continue stirring for 90 minutes.

[0035] S4. Green Post-processing and Product Collection: After the reaction is complete, the reaction system obtained in step S3 is naturally cooled to 22°C. The material in the reactor is transferred to a high-speed shear disperser and sheared at 6000 rpm for 4 minutes. The crushed slurry is then transferred to a centrifuge and centrifuged at 3800 rpm for 11 minutes to separate solid polymer particles. The solid particles are washed with deionized water to remove residual inorganic salts until the filtrate is free of halide or sulfate ions. The filtrate is then centrifuged again for dehydration. The dehydrated solid particles are pre-dried at 45°C and a vacuum of 0.065 MPa for 1.2 hours to reduce the particle moisture content to below 5%. The pre-dried wet solid particles are purified using a supercritical CO2 fluid extraction device: the extraction vessel temperature is set at 32.5°C, the pressure at 8.5 MPa, the CO2 flow rate at 18 L / h, anhydrous ethanol is used as the entrainer (flow rate of 5% of the CO2 flow rate), and the extraction time is 75 minutes. After extraction, the particles were transferred to a vacuum drying oven and dried at 48°C and a vacuum of 0.065 MPa for 2.2 hours. Finally, the dried particles were pulverized using an air jet mill and passed through a 120-mesh standard sieve. The sieve residue was collected to obtain a white to off-white functionalized cross-linked polyvinylpyrrolidone powder.

[0036] Example 2

[0037] S1. Preparation of Pre-emulsion: 220g of N-vinylpyrrolidone monomer, 60g of functionalized comonomer methacrylic acid, and 0.9g of oil-soluble initiator azobisisobutyronitrile (AIBN) were mixed in a clean container and stirred at 350 rpm for 12 minutes at 28°C until the AIBN was completely dissolved, obtaining a mixed monomer solution. Subsequently, the above mixed monomer solution, 900g of deionized water, 15g of dispersant nanocellulose (CNC), and 450g of inorganic salt sodium sulfate were sequentially added to the reactor. Stirring was started, and the mixture was continuously stirred at 500 rpm for 22 minutes until a uniform and stable milky white micro-suspension was formed.

[0038] S2. Stepwise Initiation and Dynamic Crosslinking Polymerization: The microsuspension system obtained in step S1 was heated to 72°C at a programmed heating rate of 2.5°C / min and maintained at this temperature for 70 minutes. Subsequently, the system temperature was raised to 81°C, and 1.6 g of the second initiator, benzoyl peroxide (BPO, pre-dissolved in 12 mL of anhydrous ethanol), was added to the system through the feed port. Simultaneously with the addition of the second initiator, 30 g of the specific multifunctional crosslinking agent, pentaerythritol triacrylate (PETA), was added dropwise to the reaction system at a constant rate of 1.2 g / min using a high-precision metering pump. The dropwise addition was synchronized with the reaction process and continued for 90 minutes.

[0039] S3. In-situ grafting modification: 60 minutes after adding the second initiator in step S2, under continuous stirring at 500 rpm, 12 g of pretreated high-performance modifier fluorosilane was added uniformly over 3 minutes via a constant-pressure dropping funnel (pretreatment method: fluorosilane and anhydrous ethanol were mixed at a ratio of 1 g: 1 mL, and glacial acetic acid was added dropwise to adjust the pH to 4.8; stirring was carried out at room temperature for 18 minutes). After adding the modifier, the reaction temperature was maintained at 76℃, and the reaction was continued with stirring for 130 minutes.

[0040] S4. Green Post-processing and Product Collection: After the reaction, the system was cooled to 28°C and subjected to high-speed shearing (9000 rpm, 6 minutes) and centrifugation (4200 rpm, 13 minutes) to obtain wet granules. The wet granules were washed with deionized water to remove residual inorganic salts until the filtrate was free of halide or sulfate ions. The filtrate was then centrifuged again for dehydration. The dehydrated solid granules were pre-dried at 48°C and a vacuum of 0.075 MPa for 1.5 hours to reduce the moisture content to below 5%. Purification was performed using supercritical CO2 extraction (33.5°C, 9.2 MPa, 22 L / h, with anhydrous ethanol as the entrainer at 7% of the CO2 flow rate, 85 minutes). The purified product was then vacuum dried (52°C, 0.075 MPa, 2.8 hours), air-jet pulverized, and passed through a 120-mesh sieve to obtain a white powder product.

[0041] Example 3

[0042] S1. Preparation of Pre-emulsion: 260g of N-vinylpyrrolidone monomer, 45g of functionalized comonomer bio-based itaconic acid, and 1.1g of oil-soluble initiator azobisisobutyronitrile (AIBN) were mixed in a clean container and stirred at 380 rpm for 14 minutes at 26°C until the AIBN was completely dissolved, obtaining a mixed monomer solution. Subsequently, the above mixed monomer solution, 1100g of deionized water, 18g of dispersant nanocellulose (CNC), and 550g of inorganic salt sodium chloride were sequentially added to the reactor. Stirring was started, and the mixture was continuously stirred at 550 rpm for 24 minutes until a uniform and stable milky white micro-suspension was formed.

[0043] S2. Stepwise Initiation and Dynamic Crosslinking Polymerization: The microsuspension system obtained in step S1 was heated to 74°C at a programmed heating rate of 2°C / min and maintained at this temperature for 65 minutes. Subsequently, the system temperature was raised to 82°C, and 1.8 g of the second initiator, benzoyl peroxide (BPO, pre-dissolved in 14 mL of anhydrous ethanol), was added to the system through the feed port. Simultaneously with the addition of the second initiator, 35 g of the specific multifunctional crosslinking agent, diethylene adipate, was added dropwise to the reaction system at a constant rate of 1.4 g / min using a high-precision metering pump. The dropwise addition was synchronized with the reaction process and continued for 95 minutes.

[0044] S3. In-situ grafting modification: 55 minutes after adding the second initiator in step S2, 14g of pretreated high-performance modifier polyhedral oligomeric silsesquioxane (POSS, pretreatment method: mix POSS with anhydrous ethanol at a ratio of 1g:1mL, adjust the pH to 4.3 by adding glacial acetic acid dropwise, and stir at room temperature for 16 minutes under continuous stirring at 550 rpm. After adding the modifier, maintain the reaction temperature at 77℃ and continue stirring for 140 minutes.

[0045] S4. Green Post-processing and Product Collection: After the reaction, the system was cooled to 26°C and subjected to high-speed shearing (8500 rpm, 7 minutes) and centrifugation (4300 rpm, 14 minutes) to obtain wet granules. The wet granules were washed with deionized water to remove residual inorganic salts until the filtrate was free of halide or sulfate ions. The filtrate was then centrifuged again for dehydration. The dehydrated solid granules were pre-dried at 48°C and a vacuum of 0.07 MPa for 1.5 hours to reduce the moisture content to below 5%. Purification was performed using supercritical CO2 extraction (34°C, 9.8 MPa, 24 L / h, with anhydrous ethanol as the entrainer at 9% of the CO2 flow rate, 88 minutes). The purified product was then vacuum dried (54°C, 0.08 MPa, 3 hours), air-jet milled, and passed through a 120-mesh sieve to obtain a white powder product.

[0046] Example 4

[0047] S1. Preparation of Pre-emulsion: 300g of N-vinylpyrrolidone monomer, 70g of functionalized comonomer N-vinylcaprolactam, and 1.0g of oil-soluble initiator azobisisobutyronitrile (AIBN) were mixed in a clean container and stirred at 320 rpm for 13 minutes at 29°C until the AIBN was completely dissolved, obtaining a mixed monomer solution. Subsequently, the above mixed monomer solution, 1000g of deionized water, 16g of dispersant nanocellulose (CNC), and 500g of inorganic salt sodium sulfate were sequentially added to the reactor. Stirring was started, and the mixture was continuously stirred at 480 rpm for 21 minutes until a uniform and stable milky white micro-suspension was formed.

[0048] S2. Stepwise Initiation and Dynamic Crosslinking Polymerization: The microsuspension system obtained in step S1 was heated to 71°C at a programmed heating rate of 1.8°C / min and maintained at this temperature for 55 minutes. Subsequently, the system temperature was raised to 80°C, and 1.4 g of the second initiator, benzoyl peroxide (BPO, pre-dissolved in 11 mL of anhydrous ethanol), was added to the system through the feed port. Simultaneously with the addition of the second initiator, 25 g of a specific multifunctional crosslinking agent, an L-cysteine ​​derivative containing disulfide bonds (SS), was added dropwise to the reaction system at a constant rate of 1.1 g / min using a high-precision metering pump. The dropwise addition was synchronized with the reaction process and continued for 85 minutes.

[0049] S3. In-situ grafting modification: 48 minutes after adding the second initiator in step S2, 10g of high-performance modifier hyperbranched polyamide is added to the reaction system within 3 minutes under continuous stirring at 450 rpm. After adding the modifier, the reaction temperature is maintained at 75℃, and the reaction is continued to be stirred for 120 minutes.

[0050] S4. Green Post-processing and Product Collection: After the reaction is complete, the reaction system obtained in step S3 is naturally cooled to 24°C. The material in the reactor is transferred to a high-speed shear disperser and sheared at 7000 rpm for 5 minutes. The crushed slurry is then transferred to a centrifuge and centrifuged at 4000 rpm for 12 minutes to separate solid polymer particles. The solid particles are washed with deionized water to remove residual inorganic salts until the filtrate is free of halide or sulfate ions. The filtrate is then centrifuged again for dehydration. The dehydrated solid particles are pre-dried at 45°C and a vacuum of 0.07 MPa for 1.8 hours to reduce the particle moisture content to below 5%. The pre-dried wet solid particles are purified using a supercritical CO2 fluid extraction device: the extraction vessel temperature is set to 33°C, the pressure to 9 MPa, the CO2 flow rate to 20 L / h, and anhydrous ethanol is used as the entrainer (flow rate of 10% of the CO2 flow rate). The extraction time is 80 minutes. After extraction, the particles were transferred to a vacuum drying oven and dried at 50°C and a vacuum of 0.07 MPa for 2.5 hours. Finally, the dried particles were pulverized using an air jet mill and passed through a 120-mesh standard sieve. The sieve residue was collected to obtain a white to off-white functionalized cross-linked polyvinylpyrrolidone powder.

[0051] Comparative Example 1: Except for step S1, in which 18g of nanocellulose (CNC) was replaced with an equal mass of polyvinyl alcohol (PVA-1788), all other conditions were exactly the same as in Example 3.

[0052] Comparative Example 2: Except for step S1, where CNC is not added, all other conditions are exactly the same as in Example 3.

[0053] Comparative Example 3: Except for step S2, in which 35g of divinyl adipate was replaced with an equimolar amount of N,N'-methylenebisacrylamide (MBA), all other conditions were exactly the same as in Example 3.

[0054] Comparative Example 4: Except for canceling the in-situ grafting modification in step S3 and adding a step of physical blending with 14g POSS for 30 minutes in the post-processing of step S4, the other conditions are exactly the same as those in Example 3.

[0055] Comparative Example 5: Except for the omission of in-situ grafting modification in step S3, the other conditions are exactly the same as in Example 3.

[0056] Comparative Example 6: Except for step S4, where after washing with water to remove salt and centrifugation to pre-dry, the supercritical CO2 fluid extraction purification was replaced with anhydrous ethanol washing purification (specifically: soaking and stirring in 250 mL of anhydrous ethanol for 30 minutes, filtering, and repeating the washing 3 times), after washing, dehydration and drying were carried out under the same vacuum drying conditions (54°C, 0.08 MPa, 3 hours) as in Example 3. All other conditions were exactly the same as in Example 3.

[0057] Comparative Example 7: Except for the absence of inorganic salt sodium chloride in step S1, the other conditions were exactly the same as in Example 3.

[0058] Comparative Example 8: Except for the absence of anhydrous ethanol entrainer during supercritical CO2 fluid extraction in step S4, the other conditions were exactly the same as in Example 3.

[0059] Test methods and standards 1. Particle size distribution and uniformity Test methods and equipment: A laser particle size analyzer (Malvin Mastersizer 3000) was used to measure the volumetric particle size distribution of the sample in the dispersion medium based on the principle of laser diffraction. Characteristic particle size D was recorded. 10 D 50 D 90 And calculate the span value [(D 90 -D 10 ) / D 50 The span value is used to characterize the width of the distribution; the smaller the span value, the narrower and more uniform the distribution.

[0060] Reference standard: ISO 13320:2020 "Particle size analysis - Laser diffraction method".

[0061] 2. Swelling performance test Test method: Weigh 1.0 g of dried sample (W0) and place it in 150 mL of deionized water. Under completely unconstrained conditions, allow it to swell to equilibrium at 25 °C for approximately 24 hours. Transfer the swollen gel to a 120-mesh standard sieve and allow it to drain naturally for 5 minutes (without applying any external force, squeezing, or suction). Weigh the swollen gel (W1). The swelling ratio (Q) is calculated using the formula Q = (W1 - W0) / W0.

[0062] Reference standard: The method principle is based on the relevant description of the dissolution and release determination method in the General Chapter of Part IV of the 2020 edition of the Pharmacopoeia of the People's Republic of China.

[0063] 3. Wet mechanical strength test Test methods and equipment: A texture analyzer (Stable Micro Systems TA.XT Plus) was used. The swollen, equilibrium-bound gel was formed into standard-sized cylinders, placed on the test platform, and subjected to uniaxial compression at a constant rate until the gel broke. The maximum force (F) experienced at the moment of breakage was recorded. max ), which serves as a characterization of mechanical strength.

[0064] Reference standard: ASTM F2900-11, "Guideline for Characterization of Hydrogels in Regenerative Medicine".

[0065] 4. Thermal stability analysis Test methods and equipment: A thermogravimetric analyzer was used. Under an inert gas (nitrogen) atmosphere, 5 mg of sample was heated at a constant heating rate (10°C / min), and the change in sample mass with temperature was recorded in real time to obtain the thermogravimetric (TG) curve. The temperature at which 5% weight loss occurred (T) was then recorded. d5% ) and the temperature corresponding to the maximum thermal decomposition rate (T) max ).

[0066] Reference standard: ASTM E1131-08 (2014) "Standard test method for compositional analysis by pyrolysis gravimetric analysis".

[0067] 5. Surface hydrophobicity test Test methods and equipment: A contact angle measuring instrument (Dataphysics OCA20) was used. The sample powder was pressed into a smooth, flat sheet, and a small drop of deionized water was dropped onto its surface. The droplet image was captured by a high-speed camera, and the static contact angle was calculated by fitting the Young-Laplace equation.

[0068] Reference standard: ISO 19403-3:2017 "Wetting properties of paints and varnishes - Part 3: Determination of surface tension of liquids by the pendant drop method" (measurement principle and instrumentation are universal).

[0069] 6. Determination of NVP Residue Test methods and equipment: Gas chromatography-mass spectrometry (GC-MS) was used. An appropriate amount of sample was accurately weighed and placed in a stoppered conical flask. An appropriate amount of methanol was added, and the sample was extracted by sonication at 25℃ for 30 minutes. After cooling to room temperature, the sample was filtered through a 0.22 μm organic filter membrane, and the filtrate was injected for analysis. Quantitative analysis was performed using either the external standard method or the internal standard method.

[0070] Reference standard: Refer to the "Determination of Residual Solvents" in General Chapter 0861 of Part IV of the 2025 edition of the Pharmacopoeia of the People's Republic of China.

[0071] 7. Determination of Ethanol Residue Headspace gas chromatography (HS-GC) was used, following the method for residual solvent determination in General Chapter 0861 of the 2025 edition of the Chinese Pharmacopoeia. Chromatographic conditions: DB-624 capillary column, nitrogen as carrier gas, flow rate 1.0 mL / min; injection port temperature 200℃; detector (FID) temperature 250℃; injection volume 1.0 mL, split ratio 10:1. Column temperature program: initial temperature 40℃, held for 5 min, then increased to 200℃ at 10℃ / min and held for 3 min. Headspace injection conditions: equilibration temperature 80℃, equilibration time 30 min.

[0072] 8. Tap density determination Test method: 30g of dry sample powder is placed into a clean graduated cylinder. The graduated cylinder is fixed on a tapped density meter, and the amplitude is set to 3mm and the frequency to 250 times / minute. The volume V1 is recorded after 500 vibrations, and then the volume V2 is recorded after another 750 vibrations. If V1 - V2 < 2 mL, V2 is recorded as the final volume; otherwise, vibration continues until the volume is constant. The tapped density is calculated as 30.00 / V2.

[0073] 9. Specific surface area determination Test methods and equipment: A fully automated specific surface area and porosity analyzer was used. The adsorption-desorption isotherm of nitrogen on the sample was measured at liquid nitrogen temperature, and the specific surface area of ​​the sample was calculated using the Brunauer-Emmett-Teller (BET) equation.

[0074] Reference standard: ISO 9277:2010 "Determination of specific surface area of ​​particles by gas adsorption method (BET method)".

[0075] Performance test results and analysis Table 1: Effects of different dispersion systems on product particle size and morphology (sampled within the same batch, n=3)

[0076] Table 1 shows that the median particle size (D) of the sample (Example 3) constructed using the nanocellulose (CNC) system described in this invention to create a Pickering stable system is... 50 With a particle size of only 40.5 μm and a narrow particle size distribution span of 1.08, its performance is significantly better than that of Comparative Example 1 sample (D) using a traditional PVA dispersant. 50 The sample with a diameter of 61.5 μm and a span of 1.48 μm, and the comparative sample 2 without a dispersant (D) 50 The diameter is 92.7 μm and the span is 2.27. SEM morphology comparison shows that: Figure 1 (Example 3) demonstrated excellent sphericity, with smooth microsphere surfaces and uniform particle size, showing no obvious adhesion or aggregation; while Figure 2 (Comparative Example 1) shows irregular particle shapes with a distinctly wide distribution (coexistence of large particles and small fragments). This observation further confirms that CNC can form a robust interfacial particle film at the oil / water interface, providing a strong steric hindrance effect, thereby effectively stabilizing micro-suspended droplets and inhibiting monomer droplet aggregation throughout the polymerization process. This results in the final product exhibiting superior characteristics in terms of smaller particle size, more uniform distribution, and higher sphericity.

[0077] Table 2: Effects of different crosslinking agents on the swelling properties and mechanical strength of the product (sampled within the same batch, n=3)

[0078] As shown in Table 2, the sample prepared in Comparative Example 3 (using a traditional short-chain MBA crosslinking agent) exhibits a high wet gel breaking force (2.80 N) and strong rigidity, but its swelling ratio (5.5 g / g) is much lower than that of Example 3 (18.2 g / g). This is because the network space formed by the traditional short-chain crosslinking agent is dense and rigid, severely restricting the free movement of molecular chains. In contrast, the diethylene adipate used in Example 3 of this invention, with its introduced long-chain aliphatic structure, endows the network with excellent flexibility and extensibility, resulting in a several-fold increase in swelling ratio. Although its wet breaking force (1.46 N) is lower than that of the rigid network, in practical applications, its high deformation capacity allows it to effectively dissipate internal stress during the swelling process through the stretching and slippage of the long chains, avoiding structural brittle fracture that occurs under forced stretching due to high crosslinking brittleness as in Comparative Example 3, thus achieving a synergistic balance between high swelling performance and moderate mechanical toughness.

[0079] Table 3: Effects of different modification methods on the thermal stability and surface properties of the product (sampled within the same batch, n=3)

[0080] Table 3 clearly shows that physical blending of POSS only in the later stages of polymerization (Comparative Example 4) has extremely limited effect on improving the thermal stability and hydrophobicity of the product (T). d5% 285°C, contact angle 83°), compared to the unmodified sample of Comparative Example 5 (T d5% The difference in thermal stability (T278°C, contact angle 62°) was not significant. However, the sample from Example 3, which used the method of "in-situ addition of POSS during the middle stage of polymerization" of this invention, showed little difference. d5% The performance of POSS (at 348°C) and hydrophobicity (contact angle 115°) was significantly and fundamentally improved. This proves that only by utilizing the active free radicals in the later stages of the polymerization reaction to chemically copolymerize and graft the active groups of POSS with the growing polymer chains can the inorganic rigid cage structure and hydrophobic properties of POSS be firmly integrated into the polymer network, thereby achieving a qualitative change in performance.

[0081] Table 4: Effects of different post-processing methods on product purity and physical structure (samples taken from the same batch, n=3)

[0082] Comparing the results of the two post-processing methods, the supercritical CO2 extraction technology of this invention demonstrates comprehensive advantages. The sample using this technology (Example 3) showed harmful monomer residues below the detection limit (<10 ppm), and the residual ethanol as an entrainer was undetectable, truly achieving green and residue-free processing. In contrast, the sample washed with conventional ethanol (Comparative Example 6) not only had NVP monomer residues as high as 102 ppm, but also, due to its well-developed porous network generating a strong capillary encapsulation effect during conventional drying, the residual ethanol content was as high as 2150 ppm. Furthermore, the sample prepared in Example 3 had a lower tap density (0.27 vs. 0.41 g / mL) and a higher specific surface area (16.2 vs. 8.7 m²). 2 / g). This indicates that supercritical CO2 fluid can not only more efficiently penetrate and elute small molecule impurities, but also, due to the absence of surface tension in the process, it does not damage the microporous structure inside the particles during drying, thus yielding a purer, more fluffy product with more developed pores. This technology synergistically achieves three major goals: deep purification, structural protection, and zero organic solvent residue in the product, representing a key process innovation of this invention.

[0083] Table 5: Results of the verification experiment on the synergistic effect (sampled within the same batch, n=3)

[0084] As shown in Table 5, when only nanocellulose (Comparative Example 7) is used, the particle size distribution of the product increases dramatically to 1.85. This indicates that the interfacial steric hindrance effect of nanocellulose alone is insufficient to maintain the absolute stability of the droplets. In this system, the introduction of inorganic salts is not a simple media adjustment, but rather a significant reduction in the solubility of the monomer in the aqueous phase through the salting-out effect, promoting the formation of denser primary droplets; this has a deep mechanistic synergy with the anchoring effect of nanocellulose at the interface. The significant deterioration of the particle size distribution in Comparative Example 7 confirms the interdependence and irreplaceability of the two in heterogeneous polymerization. Comparing Example 3 and Comparative Example 8, it can be seen that when there is no anhydrous ethanol entrainer, the residual amount of NVP monomer rebounds sharply from below the detection limit (<10 ppm) to 85 ppm. This result reveals the non-solventizing effect of trace amounts of ethanol here: because a highly polar microscopic water film still exists in the pores of the particles after pre-drying, it hinders the elution of polar NVP by non-polar supercritical CO2. The introduction of ethanol creates an excellent synergistic effect with supercritical CO2. This demonstrates that ethanol entrainers play an irreplaceable role in deep purification processes.

[0085] Batch stability verification To verify the repeatability and batch-to-batch stability of the process described in this invention, five batches of product were prepared independently and in parallel based on the process conditions and parameters of Example 3. Batch 1 was the first verification experiment used to establish optimal parameters (i.e., Example 3), and its data are directly cited. Batches 2 to 5 were blind samples prepared in subsequent parallel runs. Three samples were randomly selected from each of batches 2 to 5 for testing, and the average of the test results was used as the final representative data for that batch. The test results of the key performance indicators for the five batches are shown in Table 6.

[0086] Table 6: Batch stability test results of the process in Example 3.

[0087]

[0088] As shown in Table 6, the test results of the key performance indicators (particle size, swelling rate, and mechanical strength) of the five batches of products prepared according to the process of this invention are very similar, with relative standard deviations (RSD) all less than 2%. This indicates that the production process provided by this invention has excellent repeatability and reliability, and can ensure high batch-to-batch stability of product performance, thus achieving the invention's objective of high batch stability.

[0089] The above-described embodiments are merely illustrative of specific implementations of the present invention, and while the descriptions are detailed, they should not be construed as limiting the scope of protection of the present invention. It should be noted that for those skilled in the art, any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention should be considered equivalent substitutions and are included within the scope of protection of the present invention.

Claims

1. An industrial production process for cross-linked polyvinylpyrrolidone with high batch stability, characterized in that, Includes the following steps: S1. Preparation of pre-emulsion: N-vinylpyrrolidone monomer, functionalized comonomer and oil-soluble initiator are mixed and dissolved to obtain mixed monomer liquid; then the mixed monomer liquid, deionized water, dispersant and inorganic salt are mixed and stirred to form a uniform and stable micro-suspension; S2, Stepwise Initiation and Dynamic Crosslinking Polymerization: The micro-suspension system obtained in step S1 is heated to carry out the first initiation stage polymerization, and then the temperature is increased and a second initiator is added. At the same time, a specific multifunctional crosslinking agent is dynamically added to carry out the second initiation and crosslinking reaction. S3, In-situ grafting modification: When the reaction in step S2 reaches a specific stage, a high-performance modifier is added to the reaction system, and the reaction continues to achieve in-situ grafting modification; S4. Green post-processing and product collection: After cooling the reaction system obtained in step S3, solid particles are obtained by high-speed shearing and centrifugation. The solid particles are washed with deionized water to remove inorganic salts. After centrifugation and dehydration again, they are pre-vacuum dried to a moisture content of less than 5%. Then, supercritical CO2 fluid extraction technology is used, and anhydrous ethanol is used as an entrainer to purify the pre-dried wet solid particles. After drying, they are crushed and sieved to obtain functionalized modified cross-linked polyvinylpyrrolidone powder.

2. The industrial production process for high batch stability crosslinked polyvinylpyrrolidone according to claim 1, characterized in that, The preparation of the pre-emulsion in step S1 is as follows: 150-350 g of N-vinylpyrrolidone monomer, 30-80 g of functionalized comonomer and 0.5-1.2 g of oil-soluble initiator azobisisobutyronitrile are mixed and dissolved to obtain a mixed monomer solution; then the mixed monomer solution, 500-1200 g of deionized water, 8-20 g of dispersant and 200-600 g of inorganic salt are mixed and stirred at 300-600 r / min for 15-25 minutes to form a uniform and stable micro-suspension.

3. The industrial production process for high batch stability cross-linked polyvinylpyrrolidone according to claim 2, characterized in that, The functionalized comonomer in step S1 is selected from one or more of N-vinylcaprolactam, methacrylic acid, and bio-based itaconic acid; the dispersant is nanocellulose; and the inorganic salt is selected from sodium sulfate or sodium chloride.

4. The industrial production process for high batch stability crosslinked polyvinylpyrrolidone according to claim 2, characterized in that, The stepwise initiation and dynamic crosslinking polymerization in step S2 are as follows: the micro-suspension obtained in step S1 is heated to 65-75℃ at a rate of 1-3℃ / min, and the reaction is carried out for 40-80 minutes to complete the first initiation stage; then the temperature is raised to 78-82℃, 0.8-2.0 g of the second initiator benzoyl peroxide is added, and 15-40 g of multifunctional crosslinking agent is added dropwise at a constant rate of 0.8-1.5 g / min, and the dropwise addition is carried out simultaneously with the reaction for 60-100 minutes.

5. The industrial production process for high batch stability crosslinked polyvinylpyrrolidone according to claim 4, characterized in that, The specific multifunctional crosslinking agent in step S2 is selected from one of pentaerythritol triacrylate, divinyl adipate, and L-cysteine ​​derivatives containing disulfide bonds.

6. The industrial production process for high batch stability crosslinked polyvinylpyrrolidone according to claim 4, characterized in that, The in-situ grafting modification in step S3 is as follows: within 40-70 minutes after adding the second initiator in step S2, add 5-15 g of high-performance modifier to the reaction system and continue the reaction at 72-78℃ for 80-150 minutes.

7. The industrial production process for high batch stability crosslinked polyvinylpyrrolidone according to claim 6, characterized in that, The high-performance modifier in step S3 is selected from one of fluorinated silanes, hyperbranched polyamides, and polyhedral oligomeric silsesquioxanes. When the high-performance modifier is a fluorinated silane or a polyhedral oligomeric silsesquioxane, it needs to be pretreated by mixing it with anhydrous ethanol and adjusting the pH value with acid.

8. The industrial production process for high batch stability cross-linked polyvinylpyrrolidone according to claim 6, characterized in that, The green post-processing and product collection in step S4 are as follows: the reaction system is cooled to 20-30℃, and solid particles are obtained by high-speed shearing at 5000-10000r / min for 3-8 minutes and centrifugation at 3500-4500r / min for 10-15 minutes; the solid particles are washed with deionized water until the filtrate is free of halide or sulfate ions, and then centrifuged again for dehydration; the dehydrated solid particles are pre-vacuum dried at 40-50℃ and vacuum degree of 0.06-0.08MPa for 1-2 hours to reduce the water content to below 5%; supercritical CO2 fluid extraction is used for purification, with anhydrous ethanol as the entrainer at a flow rate of 5%-10% of the CO2 flow rate, and the extraction conditions are: temperature 32-34℃, pressure 8-10MPa, CO2 flow rate 15-25L / hour, and time 70-90 minutes; after drying, the particles are pulverized and passed through a 120-mesh sieve to obtain functionalized modified cross-linked polyvinylpyrrolidone powder.

9. The industrial production process of high batch stability crosslinked polyvinylpyrrolidone according to claim 8, characterized in that, In step S4, the particles after supercritical CO2 fluid extraction are dried under vacuum.

10. A functionalized modified cross-linked polyvinylpyrrolidone prepared by the industrial production process described in any one of claims 1-9.

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