High-flux and high-strength regenerated cellulose virus-removing filtering membrane as well as membrane casting solution, preparation method and application of high-flux and high-strength regenerated cellulose virus-removing filtering membrane

Abstract

The invention discloses a high-flux and high-strength regenerated cellulose virus-removing filtering membrane and a membrane casting solution, a preparation method and application thereof, the filtering membrane is of a three-dimensional structure comprising a porous liquid inlet surface and a porous liquid outlet surface, and spherical particle polymers are distributed on the porous liquid inlet surface. The preparation method has the advantages that a unique membrane structure is obtained by purely changing the split-phase form of cellulose in the membrane preparation process without cross-linking modification or other modes for modifying the surface of cellulose, so that the mechanical property of the membrane is effectively improved, and the membrane has higher membrane flux and loading capacity.

Description

Technical Field

[0001] This invention relates to the field of membrane separation technology, and in particular to a high-flux, high-strength regenerated cellulose virus-removing filtration membrane, its casting solution, preparation method, and application. Background Technology

[0002] Currently, widely used virus-removing filter membranes include synthetic polymers such as polyethersulfone (PES) and polyvinylidene fluoride (PVDF) and natural polymers such as regenerated cellulose (RC). While these materials possess certain virus-removing properties, they all have some significant drawbacks. For example, although PES has a high water flux, its natural hydrophobicity makes it prone to adsorbing biomolecules such as proteins, leading to a rapid decrease in flux when filtering biological products. This necessitates frequent membrane replacements, increasing production costs and operational complexity. PVDF suffers from similar problems to PES.

[0003] While hydrophilic modification can mitigate flux decline to some extent, the modification process is complex and lacks uniformity. Cellulose possesses naturally high hydrophilicity, giving it a potential advantage in protein filtration with low protein adsorption. However, cellulose itself has low strength and poor pressure resistance. Under high-pressure filtration, the membrane pores undergo drastic shrinkage or even collapse, resulting in a significant decrease in flux and load, severely limiting its application in high-pressure, high-flux filtration scenarios. The excellent natural hydrophilicity of cellulose has thus come to the forefront of public attention.

[0004] Asahi Kasei Medical Systems, Inc. of Japan pioneered the development and launch of the Planova series filters, capable of retaining viruses 20nm and larger. They have also applied for a patent (CN105980038A) for a virus-removing membrane, which contains cellulose and effectively retains porcine parvovirus (LRV4). While cellulose's natural hydrophilicity gives it low protein adsorption capacity, its inherent weakness limits the pressure it can withstand. Excessive filtration pressure can compress or collapse the membrane pores, reducing the final flux and load capacity, and potentially causing virus leakage.

[0005] To address this issue, the Chinese company Kobote applied for a patent (publication number CN116712868A) for a high-mechanical-strength cellulose virus-removing membrane and its preparation process. The disclosed virus-removing membrane includes a microporous membrane support layer and a cellulose layer at least partially permeated within the microporous membrane support layer. The area within the microporous membrane support layer permeated with the cellulose layer is the permeation zone, and the cellulose layer also includes a pre-filtration zone and a separation zone. Utilizing a dual-casting solution approach, two different formulations of casting solutions are sequentially cast onto the microporous support layer, artificially controlling the longitudinal pore size gradient of the cellulose membrane to improve the final membrane's pressure resistance. While this innovative process has made some progress in improving the membrane's pressure resistance, it also has some shortcomings. On the one hand, the preparation process is relatively complex, increasing production difficulty and cost; on the other hand, due to the potential for abrupt pore size changes in the transition zone between cellulose and the microporous membrane, this can, to some extent, lead to unsatisfactory membrane loading.

[0006] Cellulose is a crystalline polymer containing crystalline and amorphous regions. The amorphous regions deform to varying degrees under pressure. Cellulose molecules primarily maintain structural stability through hydrogen bonding. While hydrogen bonds possess some strength, their bond energy is weaker than strong chemical bonds such as covalent bonds. Under pressure, these hydrogen bonds are easily broken, leading to weakened intermolecular bonding. Once the hydrogen bonds are broken, the cellulose molecular chains become more loosely connected. Therefore, the inherent characteristics of cellulose result in poor pressure resistance. Consequently, many researchers have explored various methods to improve the pressure resistance of cellulose, the most common being cross-linking modification. Different cross-linking agents are grafted onto the active hydroxyl groups on the cellulose surface to obtain cellulose with varying pressure resistance. However, for regenerated cellulose porous membranes, cross-linking affects the pore size to varying degrees; even the smallest degree of cross-linking significantly impacts the pore size and uniformity. Other researchers have also improved the strength and pressure resistance of cellulose by altering the degree of esterification on the cellulose surface. Although this method can effectively improve the strength of cellulose membranes, it mainly reduces the sodium hydroxide hydrolysis time or sodium hydroxide concentration, which not only affects the crystallinity of regenerated cellulose and thus the final pore size of the membrane, but also changes the hydrophilicity of the membrane, causing irreversible adsorption during the filtration of protein solutions and reducing the membrane load.

[0007] Currently, there are two methods for preparing regenerated cellulose porous membranes: cuprammonium cellulose regenerated porous membranes and cellulose ester porous membranes through hydrolysis and regeneration. Both methods can produce virus-removing filtration membranes with a 20nm filter cutoff by adjusting the formulation and membrane fabrication process. The cuprammonium method for regenerating cellulose virus-removing membranes involves dissolving cellulose raw materials such as wood pulp or cotton pulp in a specific cuprammonium ratio, followed by solvent-free regeneration to create a porous membrane. However, due to the special properties of the cuprammonium solution, the diversity of formulations is limited, potentially preventing adjustments to the membrane's structural properties and ultimately altering its performance. Furthermore, the ammonia used has a strong, irritating odor, posing a risk to human health and safety. In comparison, the method using cellulose esters as raw materials and then preparing regenerated cellulose through hydrolysis is more suitable for preparing regenerated cellulose porous membranes with different properties and applications. Summary of the Invention

[0008] The purpose of this invention is to provide a high-flux, high-strength regenerated cellulose virus-removing filtration membrane, its casting solution, preparation method, and application. Without crosslinking modification or other methods of modifying the cellulose surface, the invention simply changes the phase separation form during the membrane preparation process to obtain a unique membrane structure. This not only effectively improves the mechanical properties of the membrane but also has high membrane flux and loading capacity.

[0009] The above-mentioned technical objective of the present invention is achieved through the following technical solution:

[0010] A high-flux, high-strength regenerated cellulose virus-removing filter membrane, wherein the filter membrane has a three-dimensional structure comprising a porous inlet surface and a porous outlet surface, and the porous inlet surface is distributed with spherical polymer particles.

[0011] Preferably, the pore size of the porous inlet surface is 100~5000nm, the pore size of the porous outlet surface is 15~25nm, the average pore size is 15~35nm, the membrane porosity is 40~70%, and the membrane thickness is 30~80μm.

[0012] Preferably, the membrane water flux of the filter membrane is 80~300LMH@30psi, and the pp7 retention result is greater than or equal to 4.

[0013] Preferably, the maximum force of the filter membrane is not less than 6N and the elongation at break is not less than 45%.

[0014] A casting solution for preparing a high-flux, high-strength regenerated cellulose virus-removing filter membrane, wherein the casting solution comprises, by weight percentage: 15-25 wt% cellulose polymer, 40-60 wt% organic solvent, 20-40 wt% pore-forming agent, and 0.2-2.5 wt% polyamine small molecule substance, wherein the organic solvent is a low-boiling-point solvent or a mixed solvent formed by combining a low-boiling-point solvent and a high-boiling-point solvent.

[0015] Preferably, the cellulose polymer is selected from at least one of cellulose diacetate, cellulose triacetate, cellulose propionate, cellulose acetate phthalate, cellulose acetate butyrate, or cellulose acetate propionate.

[0016] Preferably, the low-boiling-point solvent is selected from one or more of acetone, 1,4-dioxane, acetic acid, or formic acid, and the high-boiling-point solvent is selected from one or more of N,N-dimethylformamide, N,N-dimethylacetamide, or N-methylpyrrolidone. The mixing volume ratio of the low-boiling-point solvent to the high-boiling-point solvent in the mixed solvent is 1:1 to 1.5.

[0017] Preferably, the pore-forming agent is selected from one or more of polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, methanol, or ethanol.

[0018] Preferably, the polyamine small molecule is selected from one or more of ethylenediamine, 1,3-propanediamine, diethylenetriamine, triethylenetetramine, or spermidine.

[0019] A method for preparing a high-throughput, high-strength regenerated cellulose virus-removing filter membrane, using the above-mentioned casting solution.

[0020] A method for preparing a high-flux, high-strength regenerated cellulose virus-removing filter membrane includes the following steps: S1: Add cellulose polymers, solvents, pore-forming agents and polyamine small molecules to a three-necked flask in sequence, then place it in a water bath and stir to dissolve. Once the dissolution is complete, the casting solution is obtained. Remove the solution and let it cool to room temperature for later use. S2: Take the casting liquid cooled to room temperature and cast it in a glass plate. Use a doctor blade to scrape the film. Immediately place the scraped liquid film in a coagulation bath. After the film is solidified, wash the film in pure water to obtain a porous cellulose acetate membrane. S3: Immerse the prepared cellulose acetate membrane in sodium hydroxide solution for hydrolysis. After hydrolysis, wash off the sodium hydroxide on the surface in pure water to obtain a high-flux, high-strength regenerated cellulose virus-removing filter membrane.

[0021] Preferably, in step S1, the dissolution temperature of the water bath is 40~120℃, the stirring speed is 30~300rpm, and the stirring time is 2~30h.

[0022] Preferably, in step S2, the blade gap is 250 μm, the film scraping speed is 0.2~2 m / min, the film scraping temperature is 5~35℃, and the air flow rate is 0~10 m / s.

[0023] Preferably, in step S2, the coagulation bath is a blended solution of small molecule alcohol and water at a mass ratio of 1:3~4, the temperature of the coagulation bath is 15~55℃, the standing time is 2~20min, the pure water washing temperature is 15~55℃, and the washing time is 5~30min.

[0024] Preferably, the small molecule alcohol is selected from methanol, ethanol, or propanol.

[0025] Preferably, in step S3, the concentration of the sodium hydroxide solution is 0.01~1 mol / L, the hydrolysis temperature is 25~90℃, the hydrolysis time is 3~24h, and the temperature of the washing pure water is 25℃.

[0026] Application of a high-flux, high-strength regenerated cellulose virus-removing filter membrane in virus removal.

[0027] Preferably, the virus is present in a biological product, which is an immunoglobulin, a vaccine, or a recombinant protein drug.

[0028] In summary, the present invention has the following beneficial effects: 1. This invention utilizes the high melting point characteristics of cellulose polymers and employs a non-solvent-induced phase inversion method (NIPS), a low-cost, convenient, and effective method for preparing porous cellulose membranes. The basis of NIPS membrane fabrication is liquid-liquid phase separation. Based on the location of liquid-liquid phase separation in the ternary phase diagram, liquid-liquid phase separation can be divided into nucleation growth phase separation and spiral phase separation. Nucleation growth phase separation that does not pass through the critical point can be further divided into two categories based on the position of the casting solution system entering the phase separation region: one category involves the casting solution system entering the metastable region from below the critical point, resulting in polymer-rich phase nucleation and the formation of latex particle structures; the other category involves the casting solution system entering the metastable region from above the critical point, resulting in polymer-depleted phase nucleation and the formation of porous structures. For spiral phase separation that passes through the critical point, since the system composition directly reaches the unsteady phase separation region, the system instantly forms a liquid-liquid phase separation system with interleaved polymer-depleted phase microregions (depleted phase) and polymer-rich phase microregions (rich phase), resulting in a bicontinuous membrane structure. While polymer-rich nucleation produces excellent mechanical properties, it results in a wide pore size distribution and low porosity. Conversely, polymer-poor nucleation produces excellent pore size distribution and porosity, but lower mechanical strength. Therefore, this invention separates the system from the critical point into a metastable state, first forming an interleaved structure of polymer-poor and polymer-rich phases, and then entering a metastable state below the critical point. The main phase separation occurs through polymer-poor nucleation. In this way, the prepared porous membrane possesses both porosity and mechanical strength.

[0029] 2. This invention first increases the content of cellulose polymers in the solution to avoid phase separation caused by low solids content, which would result in the final phase separation occurring through the nucleation of a lean polymer phase. To ensure this phase separation, the organic solvent used is a low-boiling-point solvent or a mixture of high-boiling-point and low-boiling-point solvents. This aims to ensure that the casting solution undergoes phase separation through the nucleation of a rich polymer phase. Furthermore, polyamine small molecules are added to the casting solution of this invention to artificially create a large amount of lean polymers, allowing for film formation in the early stages of film formation through alternating rich and lean phases, followed by film formation through the nucleation of lean polymers in the later stages. More importantly, these amine small molecules are highly reactive amines, which, upon addition to the casting solution, can rapidly form hydrogen bonds with the hydroxyl groups on the surface of the cellulose polymers, causing a dramatic coiling of the cellulose polymer molecular weight. This results in the formation of a large number of spherical particles in the casting solution during subsequent phase separation, followed by the formation of a porous membrane with a large amount of linear polymers. Therefore, these particulate polymers can be clearly observed on the inlet surface in the electron microscope image. These particulate polymers provide excellent porosity for the overall membrane. Unlike single-phase depleted membrane formation, the regenerated cellulose virus-removing filter membrane prepared in this invention undergoes phase separation of both depleted and enriched phases simultaneously. As a result, a large number of cellulose polymer molecular chains form a "network," which provides a good mechanical strength basis for the final regenerated cellulose virus-removing filter membrane. Attached Figure Description

[0030] Figure 1 This is a cross-sectional electron microscope image of the high-throughput, high-strength regenerated cellulose virus-removing filter membrane prepared in Example 1 of the present invention.

[0031] Figure 2 This is an electron microscope image of the inlet surface of the high-throughput, high-strength regenerated cellulose virus-removing filter membrane prepared in Example 1 of this invention.

[0032] Figure 3 This is an electron microscope image of the inlet surface of the high-throughput, high-strength regenerated cellulose virus-removing filter membrane prepared in Comparative Example 1 of this invention.

[0033] Figure 4 This is a schematic diagram of the SEM structure of the high-throughput, high-strength regenerated cellulose virus-removing filter membrane prepared in Example 1 of the present invention. Detailed Implementation

[0034] The specific embodiments of the present invention will be further described below with reference to the accompanying drawings. These embodiments do not constitute a limitation on the present invention.

[0035] Example 1 Add 20g cellulose diacetate, 55g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 70μm.

[0036] Example 2 Add 20g cellulose diacetate, 55g acetone, 23.5g polyethylene glycol 200, and 1.5g 1,3-propanediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 66μm.

[0037] Example 3 Add 20g cellulose diacetate, 55g acetone, 24.5g polyethylene glycol 200, and 0.5g diethylenetriamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 69μm.

[0038] Example 4 Add 20g cellulose diacetate, 55g acetone, 24.8g polyethylene glycol 200, and 0.2g triethylenetetramine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 68μm.

[0039] Example 5 Add 20g cellulose diacetate, 55g acetone, 23g polyethylene glycol 200, and 2g spermidine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 67μm.

[0040] Example 6 Add 20g cellulose diacetate, 55g dioxane, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 63μm.

[0041] Example 7 Add 20g cellulose diacetate, 55g acetic acid, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 58μm.

[0042] Example 8 Add 20g cellulose diacetate, 25g acetone, 30g DMAc, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 55μm.

[0043] Example 9 Add 20g cellulose diacetate, 25g acetone, 30g NMP, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 61μm.

[0044] Example 10 Add 20g cellulose diacetate, 55g acetone, 24g polyvinylpyrrolidone K10, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 72μm.

[0045] Example 11 Add 20g cellulose diacetate, 55g acetone, 24g ethanol, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 56μm.

[0046] Example 12 Add 20g cellulose triacetate, 55g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 65μm.

[0047] Example 13 Add 20g cellulose propionate, 55g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 66μm.

[0048] Example 14 Add 20g of cellulose acetate butyrate, 55g of acetone, 24g of polyethylene glycol 200, and 1g of ethylenediamine to a three-necked flask. Stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and then store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 68μm.

[0049] Example 15 Add 20g cellulose diacetate, 55g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 30% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 63μm.

[0050] Example 16 Add 20g cellulose diacetate, 55g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 70% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 70μm.

[0051] Example 17 Add 20g cellulose diacetate, 55g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% methanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 62μm.

[0052] Example 18 Add 20g cellulose diacetate, 55g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and then store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 50℃, 0.01mol / L NaOH aqueous solution for 36 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 68μm.

[0053] Example 19 Add 20g cellulose diacetate, 55g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 60℃, 0.5mol / L NaOH aqueous solution for 10 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 69μm.

[0054] Example 20 Add 20g cellulose diacetate, 55g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in an 80℃, 1mol / L NaOH aqueous solution for 3 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 62μm.

[0055] Comparative Example 1 Add 20g of cellulose diacetate, 55g of acetone, and 25g of polyethylene glycol 200 to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and then store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 48μm.

[0056] Comparative Example 2 Add 25g of cellulose diacetate, 50g of acetone, and 25g of polyethylene glycol 200 to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 55μm.

[0057] Comparative Example 3 Add 15g cellulose diacetate, 60g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 54μm.

[0058] Comparative Example 4 Add 30g of cellulose diacetate, 45g of acetone, and 25g of polyethylene glycol 200 to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 61μm.

[0059] Comparative Example 5 Add 20g cellulose diacetate, 55g DMF, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 43μm.

[0060] Comparative Example 6 Add 30g cellulose diacetate, 45g DMF, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 48μm.

[0061] Comparative Example 7 Add 20g cellulose diacetate, 55g acetone, 20g polyethylene glycol 200, and 5g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 62μm.

[0062] Comparative Example 8 Add 20g cellulose diacetate, 55g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. After coating, allow the film to stand in air for 30 seconds, then immerse it in a 25℃, 50% ethanol aqueous solution to solidify for 5 minutes. After film formation, immerse the film in 25℃ pure water for 5 minutes and store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 66μm.

[0063] Comparative Example 9 Add 20g cellulose diacetate, 55g acetone, 24g polyethylene glycol 200, and 1g ethylenediamine to a three-necked flask and stir in a 50℃ water bath for 8 hours until the casting solution becomes a homogeneous and transparent solution. Remove the flask and allow it to cool to room temperature to remove bubbles. Cast the cooled casting solution onto a glass plate and use a 250μm gap doctor blade at a speed of 1m / min to uniformly coat the film. Immediately after coating, immerse the film in a 25℃ pure aqueous solution for 5 minutes to solidify. After film formation, immerse the film in 25℃ pure water for 5 minutes and then store it in pure water for later use. Hydrolyze the prepared cellulose acetate membrane in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. Then, wash the membrane in 25℃ pure water to remove the surface alkali. The final membrane thickness is approximately 59μm.

[0064] Comparative Example 10 20g of cellulose diacetate, 55g of acetone, 24g of polyethylene glycol 200, and 1g of ethylenediamine were added to a three-necked flask and stirred in a 50℃ water bath for 8 hours until the casting solution became a homogeneous and transparent solution. The solution was then removed and allowed to cool at room temperature to remove bubbles. The cooled casting solution was cast onto a glass plate and uniformly scraped using a 250μm gap doctor blade at a speed of 1m / min. After scraping, the film was immediately immersed in a 25℃, 99.9% ethanol solution to solidify for 5 minutes. After film formation, the film was immersed in 25℃ pure water for 5 minutes and then stored in pure water for later use. The prepared cellulose acetate membrane was hydrolyzed in a 30℃, 0.05mol / L NaOH aqueous solution for 24 hours to obtain a regenerated cellulose porous membrane. The membrane was then washed in 25℃ pure water to remove the surface alkali. However, this comparative example ultimately failed to form a complete membrane.

[0065] Performance testing The regenerated cellulose virus-removing filter membranes in Examples 1-20 and Comparative Examples 1-10 were tested.

[0066] Average pore size test: The test was conducted using a Bestar (BSD-PB-PBL) pore size distribution tester. The filter membrane was cut to the required size for the equipment. Water was gradually displaced from the initially wet membrane using ethanol of varying concentrations. Then, it was wetted with a low surface tension (15.6 mN / m) solvent (provided by the equipment supplier), placed in the test tank, and finally dried. The wet line yields the average pore size and the initial pore size at which bubbles begin to emerge.

[0067] Average surface pore size: The front, back and side of the membrane are scanned and photographed using a scanning electron microscope. The average value is calculated by measuring the images using computer software (such as Matlab, NIS-Elements, Nano Measurer 1.2, etc.) or manually.

[0068] Water flux: Tested using a Millipore 25mm stainless steel replaceable membrane filter, with an effective filtration area of ​​4.1cm². 2 The filtration test was conducted using ultrapure water at a temperature of 25°C and a pressure of 30 psi.

[0069] Protein loading: The loading test was still conducted using a Millipore Virusmax testing device with a 25mm stainless steel replaceable membrane filter. The effective filtration area was 4.1cm². 2 The target protein solution was tested at a temperature of 25°C and a pressure of 30 psi.

[0070] Virus Retention Test: Using polyclonal antibody IgG as the antibody solution, 5% MVM mouse parvovirus was added to the resulting antibody solution, and the mixture was thoroughly stirred to obtain an antibody solution containing the virus. The test was performed using a Millipore Virusmax test device with a 25mm stainless steel membrane filter. The calculation formula is as follows: LRV = log10(C0 / C F ).

[0071] Where: C0 represents the infection titer of the stock solution containing antibodies against the virus, C F This indicates the infection titer in the filtrate after using a high-strength cellulose virus-removing filter membrane.

[0072] Tensile testing: The moistened regenerated cellulose membrane was cut into dumbbell-shaped strips (4 mm wide, 20 mm gauge length) using a CMT6104 universal testing machine from Metersbonwe Industrial Systems, Inc., USA. The strips were then tested using the universal testing machine at a speed of 1 mm·min⁻¹. -1 Tensile tests were conducted at a certain speed.

[0073] The specific test data are shown in Tables 1 and 2 below.

[0074] Table 1 Structural data and mechanical properties of regenerated cellulose filter membranes

[0075] From Table 1, the average pore size at the inlet and outlet of Examples 1-20 clearly shows that the membrane as a whole still exhibits a certain degree of asymmetry. This is further supported by the electron microscope images obtained. Figure 1 It can be observed that a macroporous structure of a certain thickness exists at the liquid inlet surface. This macroporous structure has a good pre-filtration effect, effectively filtering out large aggregates in the protein solution, thereby reducing the final flux decline. By comparing Examples 1-5 with the comparative example, it is very clear that amine small molecules can be used to prepare 20nm porous membranes. This is because these substances form a relatively stable hydrogen bond structure with cellulose polymers, resulting in a slower pore-forming rate during phase separation and the uniform formation of small pores. Furthermore, compared with Comparative Example 1, Examples 1-5 exhibit significantly superior mechanical properties. This is because the membranes primarily utilize a phase-rich formation method during the later phase separation process, forming a large number of entangled networks between the membranes, similar to a certain degree of physical cross-linking. Numerous spherical particles then combine with a large number of linear polymers to form a porous membrane, such as... Figure 2 As shown, this not only provides the porous membrane with excellent mechanical properties but also excellent pressure resistance. Simply adding amine molecules to the formulation also fails to successfully prepare a porous membrane capable of retaining 20nm viruses. Data from Comparative Examples 3 and 5 show that besides amine molecules being a key factor in preparing virus-removing filtration membranes, the solvent and cellulose polymer are also crucial factors. This is because using a single high-boiling-point solvent results in insufficient solvent evaporation during film formation, ultimately leading to a less compact overall membrane structure and excessively high porosity. Furthermore, the low solid content of the cellulose polymer results in phase separation in both the early and late stages of membrane formation, primarily through depleted phase nucleation, also contributing to a looser final membrane structure and higher overall porosity, making it unable to retain 20nm viruses. Figure 3 As shown. It is noteworthy that the experiments in Comparative Example 10 failed to form a film. This is because when pure ethanol was used as the coagulation bath, the overall surface tension was low. When the liquid film containing small amine molecules was immersed in a substance with low surface tension, it was not easy for phase separation to occur, so a film could not be formed in the end.

[0076] Table 2 Performance test results of regenerated cellulose filter membrane

[0077] Table 2 shows the water flux, virus rejection, protein load at different concentrations, and different filtration pressures for the different examples and comparative examples. The regenerated cellulose virus-removing filter membranes of Examples 1-20 exhibit high water flux and virus rejection capabilities. Compared to the comparative examples, this demonstrates that even with high cellulose polymer solid content and the presence of small molecule amines, using low-boiling-point solvents or a combination of low- and high-boiling-point solvents can produce excellent virus-removing filter membranes with high water flux, virus rejection, and protein load. The protein load test results at different loads indicate that this virus-removing membrane is not suitable for filtering protein solutions with concentrations exceeding 30 g / L, as the load drops sharply. However, after increasing the filtration pressure, Examples 1-20 showed varying degrees of increase in load after filtering a 50 g / L protein solution, while the membranes of Comparative Examples 1-6 showed varying degrees of damage. This is because the porous membranes prepared in these six experiments lacked high pressure resistance; increasing the filtration pressure caused severe pore collapse, leading to irreversible damage. It is worth noting that Comparative Example 8 also has a very high virus retention capacity. This is because when the liquid membrane is subjected to air phase separation for a certain period of time, most of the solvent evaporates, and the cellulose polymer chains in it undergo violent entanglement, resulting in a smaller overall pore size of the membrane, which enables it to retain viruses. However, pore size testing shows that the overall pore size of the membrane is close to the size of proteins, which results in its low protein load performance.

[0078] The above results demonstrate that the solution of the present invention is significantly superior to the prior art in terms of throughput, virus retention, and mechanical strength.

[0079] This invention avoids phase separation due to low solids content and the nucleation of the depleted polymer phase by first increasing the content of cellulose polymers in the solution. To ensure this phase separation, the organic solvent used is a low-boiling-point solvent or a mixture of high-boiling-point and low-boiling-point solvents. This aims to ensure that the casting solution undergoes phase separation by the nucleation of the rich-phase polymer. Furthermore, polyamine small molecules are added to the casting solution of this invention to artificially create a large amount of depleted polymers, allowing for film formation in the early stages of film formation through alternating rich and depleted phases, followed by film formation by the nucleation of the depleted polymers in the later stages. More importantly, these amine small molecules are highly reactive amines, which, upon addition to the casting solution, can rapidly form hydrogen bonds with the hydroxyl groups on the surface of the cellulose polymers, causing a dramatic coiling of the cellulose polymer's molecular weight. This results in the formation of a large number of spherical particles in the casting solution during subsequent phase separation, followed by the formation of a porous membrane with a large amount of linear polymers. Figure 4 As shown. Therefore, in Figure 2These particulate polymers can be clearly observed in the electron microscope images of the inlet surface. These particulate polymers provide excellent porosity for the membrane as a whole. Unlike membranes formed by a single depleted phase, the regenerated cellulose virus-removing filter membrane prepared in this invention undergoes phase separation of both depleted and enriched phases simultaneously. Therefore, a large number of cellulose polymer molecular chains form a "network," which provides a good mechanical strength basis for the final regenerated cellulose virus-removing filter membrane.

[0080] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art can make various modifications or equivalent substitutions to the present invention within the scope of its essence and protection. Such modifications or equivalent substitutions should also be considered to fall within the protection scope of the present invention.

Claims

1. A high-flux, high-strength regenerated cellulose virus-removing filter membrane, characterized in that, The filter membrane has a three-dimensional structure comprising a porous inlet surface and a porous outlet surface, wherein spherical polymer particles are distributed on the porous inlet surface.

2. The high-flux, high-strength regenerated cellulose virus-removing filter membrane according to claim 1, characterized in that, The pore size of the porous inlet surface is 100~5000nm, the pore size of the porous outlet surface is 15~25nm, the average pore size is 15~35nm, the membrane porosity is 40~70%, and the membrane thickness is 30~80μm.

3. The high-flux, high-strength regenerated cellulose virus-removing filter membrane according to claim 1, characterized in that, The membrane water flux of the filter membrane is 60~300LMH@30psi, and the pp7 retention result is greater than or equal to 4.

4. The high-flux, high-strength regenerated cellulose virus-removing filter membrane according to claim 1, characterized in that, The maximum force of the filter membrane is not less than 6N, and the elongation at break is not less than 45%.

5. A casting solution for preparing a high-flux, high-strength regenerated cellulose virus-removing filtration membrane as described in any one of claims 1 to 4, characterized in that, The casting solution comprises, by weight percentage: 15-25 wt% cellulose polymer, 40-60 wt% organic solvent, 20-40 wt% pore-forming agent, and 0.2-2.5 wt% polyamine small molecule substance, wherein the organic solvent is a low-boiling-point solvent or a mixed solvent formed by combining a low-boiling-point solvent and a high-boiling-point solvent.

6. The casting solution according to claim 5, characterized in that, The cellulose polymer is selected from at least one of cellulose diacetate, cellulose triacetate, cellulose propionate, cellulose acetate phthalate, cellulose acetate butyrate, or cellulose acetate propionate.

7. The casting solution according to claim 5, characterized in that, The low-boiling-point solvent is selected from one or more of acetone, 1,4-dioxane, acetic acid, or formic acid, and the high-boiling-point solvent is selected from one or more of N,N-dimethylformamide, N,N-dimethylacetamide, or N-methylpyrrolidone. The mixing volume ratio of the low-boiling-point solvent to the high-boiling-point solvent in the mixed solvent is 1:1 to 1.

5.

8. The casting solution according to claim 5, characterized in that, The pore-forming agent is selected from one or more of polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, methanol, or ethanol.

9. The casting solution according to claim 5, characterized in that, The polyamine small molecule is selected from one or more of ethylenediamine, 1,3-propanediamine, diethylenetriamine, triethylenetetramine, or spermidine.

10. A method for preparing a high-flux, high-strength regenerated cellulose virus-removing filter membrane, characterized in that, The casting solution described in any one of claims 5 to 9 is used for preparation.

11. The method for preparing a high-flux, high-strength regenerated cellulose virus-removing filter membrane according to claim 10, characterized in that, Includes the following steps: S1: Add cellulose polymers, solvents, pore-forming agents and polyamine small molecules to a three-necked flask in sequence, then place it in a water bath and stir to dissolve. Once the dissolution is complete, the casting solution is obtained. Remove the solution and let it cool to room temperature for later use. S2: Take the casting liquid cooled to room temperature and cast it in a glass plate. Use a doctor blade to scrape the film. Immediately place the scraped liquid film in a coagulation bath. After the film is solidified, wash the film in pure water to obtain a porous cellulose acetate membrane. S3: Immerse the prepared cellulose acetate membrane in sodium hydroxide solution for hydrolysis. After hydrolysis, wash off the sodium hydroxide on the surface in pure water to obtain a high-flux, high-strength regenerated cellulose virus-removing filter membrane.

12. The method for preparing a high-flux, high-strength regenerated cellulose virus-removing filter membrane according to claim 11, characterized in that, In step S1, the dissolution temperature of the water bath is 40~120℃, the stirring speed is 30~300rpm, and the stirring time is 2~30h.

13. The method for preparing a high-flux, high-strength regenerated cellulose virus-removing filter membrane according to claim 11, characterized in that, In step S2, the blade gap is 250 μm, the film scraping speed is 0.2~2 m / min, the film scraping temperature is 5~35℃, and the air flow rate is 0~10 m / s.

14. The method for preparing a high-flux, high-strength regenerated cellulose virus-removing filter membrane according to claim 11, characterized in that, In step S2, the coagulation bath is a blended solution of small molecule alcohols and water at a mass ratio of 1:3 to 4. The temperature of the coagulation bath is 15 to 55°C, and the holding time is 2 to 20 minutes. The pure water washing temperature is 15 to 55°C, and the washing time is 5 to 30 minutes.

15. The method for preparing a high-flux, high-strength regenerated cellulose virus-removing filter membrane according to claim 14, characterized in that, The small molecule alcohols are selected from one of methanol, ethanol, or propanol.

16. The method for preparing a high-flux, high-strength regenerated cellulose virus-removing filter membrane according to claim 11, characterized in that, In step S3, the concentration of the sodium hydroxide solution is 0.01~1 mol / L, the hydrolysis temperature is 25~90℃, the hydrolysis time is 3~24h, and the temperature of the pure water used for washing is 25℃.

17. The application of a high-throughput, high-strength regenerated cellulose virus-removing filter membrane as described in any one of claims 1 to 4 in virus removal.

18. The application according to claim 17, characterized in that, The virus is present in biological products, which are immunoglobulins, vaccines, or recombinant protein drugs.

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