JPS63236501A - Hollow yarns for separating and removing virus - Google Patents

Abstract

PURPOSE:To prepare hollow yarns for separating virus without lowering biological activity of protein and without lowering filtering speed by using regenerated cellulose of specific values of average pore diameters, surface void content, minimum average pore diameter, minimum surface void content and wall thickness and having a lamellar structure in the membrane thickness direction. CONSTITUTION:Mixed solution of acetone, ammonia and water is turned into a hollowing agent and a coagulating agent by using spinning stock solution composed of, for instance, cellulose linters dissolved in copper ammonia solution, and spinning hollow yarns while controlling the temperature strictly; after microphase separation is slowly developed from the inner and outer walls toward the inner section, the same is regenerated into cellulose with sulfuric water solution or the like. Thus hollow yarns of 10-100nm pore diameters 0.25 or more inner surface void content, 0.02-0.2mum micro-average pore diameters, 0.05-0.5 micro-inner surface void content and having a lamellar structure of 10 layers or more in the membrane thickness direction and 10mum or more wall thickness are prepared.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a hollow fiber for separating and removing viruses in an aqueous solution, particularly in an aqueous solution containing 1% or more of protein.

Not only bacteria but also viruses must not be found in injectable drug solutions such as plasma fraction preparations. Recently, it has been considered that contamination with inactivated bacteria or viruses is also undesirable. In addition, virus contamination must be avoided as much as possible in genetic engineering or fermentation engineering.

[Conventional technology]

Conventionally, gel filtration, centrifugation, and adsorption separation methods have been proposed on a laboratory scale as methods for removing viruses mixed in aqueous solutions. The gel filtration method cannot completely remove a large amount of viruses and is not at a stage where it can be applied industrially.The centrifugation method is difficult to remove when the diameter of the virus is relatively large and there is a difference between the density of the virus and the density of the aqueous solution. This method can be applied only when the viscosity of the aqueous solution is low, but if this method is to be implemented industrially, there are many problems such as the need to increase the size of the equipment. Although it is possible to remove a small amount of a specific virus using the adsorption separation method, it is difficult to remove a large amount of all viruses when a large number of viruses are mixed, and there is no guarantee of stable removal ability at all times. .

Although ultrafiltration is a promising method for removing all kinds of viruses, it is hardly used industrially. Furthermore, even on a laboratory scale, it is difficult to reduce the virus particles in the filtrate to 1/10' to 1/10'' of the concentration of the filter agent using a porous polymer membrane, considering the pore size distribution of the porous polymer membrane. It was considered possible.Actually, using the water filtration rate method, an aqueous solution containing Escherichia coli phage φ×174 with a particle size of 24 nm was filtered using a polyacrylic acid-based asymmetric membrane with an average pore size of about 2 nm. The virus concentration in the filtrate is 1/1 of the virus concentration in the filter agent.
0' to 1/10' only, 1/10' to l/1"O
It doesn't reach I+.

On the other hand, to increase the virus removal rate, the average pore diameter should be 10 nm.
If it is below, not only will the filtration rate decrease, but the useful protein concentration in the filtrate will be less than 10% of the concentration before filtration.

In particular, when the protein concentration in the aqueous solution before filtration is 1% or more, the filtration rate decreases rapidly, and sometimes a cake layer appears on the membrane surface.

On the other hand, a method for removing viruses from an aqueous solution using a homogeneous symmetrical membrane is disclosed in JP-A-60-142860.

There is a method described in Japanese Unexamined Patent Publication No. 142861/1986.

This method discloses a membrane having an effective thickness of 5 μm or more and a homogeneous membrane structure, particularly a membrane composed of polyolefin. There is no description of any experimental evidence that in the method using this membrane, the virus concentration in the filtrate from a solution with a protein concentration of 1% or more was less than 1/10' of that in the original solution. Furthermore, when an aqueous solution with a protein concentration of 1% is filtered, or when the transmembrane pressure is increased to 200 mmHg or more, the filtration rate decreases over time or the protein concentration in the filtrate decreases significantly, making it impossible to obtain stable filtration characteristics. , it is difficult to utilize this industrially. Furthermore, the biological activity of the obtained filtrate is significantly lower than that before filtration. In other words, methods using asymmetric or homogeneous symmetric porous polymer membranes have the contradictory problems of providing high virus removal rate, high filtration rate, and high protein permeability while not creating a cake layer on the membrane surface. point is not resolved.

[Problem that the invention seeks to solve]

If the average pore diameter of the porous polymer membrane is reduced, the virus inhibition rate will increase, but the filtration rate will decrease and the protein concentration in the filtrate will decrease. If the average pore diameter becomes large, the virus inhibition rate will be less than 99%, and the film will not be able to function as a virus removal membrane.

Viruses in an aqueous solution can be separated and removed in a short period of time without causing denaturation of proteins in the aqueous solution or a decrease in the biological activity of plasma or plasma fraction preparations. A first object of the present invention is to provide a porous hollow fiber with high velocity. Furthermore, the biological activity of the protein present in the filtrate is not lower than that in the stock solution, and the permeation rate of protein into the filtrate is 75%.
A second object of the present invention is to provide a polymeric porous hollow fiber having a polypropylene content of at least %.

[Means for solving problems]

The present invention is made of regenerated cellulose, has an average pore diameter of 10 to 100 rv+ by water filtration rate method, and has an in-plane porosity (Pre).
is 0.25 or more, and the minimum average pore diameter is 0.02 to 0.2 μm
, has a minimal in-plane porosity (Pre') of 0.05 to 0.5, has a layered structure with 10 or more layers in the film thickness direction, and has a hollow fiber wall thickness (T, in μm). ) is 10μ
The present invention relates to a porous hollow fiber for virus separation and removal, characterized in that the porous hollow fiber has a diameter of at least m.

In the present invention, it is extremely important to use regenerated cellulose as the material for the hollow fibers. Porous hollow fibers made from regenerated cellulose have clearly visible pores when the inner and outer wall surfaces are observed using a scanning electron microscope.
It means a hollow fiber in which the abundance ratio (area ratio) of pores is 5% or more, and 90% or more of the material is composed of cellulose molecules. Regenerated cellulose has extremely low protein adsorption in an aqueous protein solution or in physiological saline. Comparing the same membrane surface area, the amount of protein adsorbed is 17% compared to conventionally known products such as polyolefins and cellulose esters.
3 or less. Moreover, the desorption of protein after adsorption is extremely rapid; for example, when the hollow fiber of the present invention on which protein has been adsorbed is immersed in physiological saline, the protein is immediately desorbed.

Among regenerated cellulose, cuprammonium regenerated cellulose is most desirable. Here, the copper ammonium regenerated cellulose (abbreviated as copper ammonium cellulose) means cellulose obtained by regenerating cellulose from a copper ammonium solution.

Ammonium ammonium cellulose adsorbs proteins in aqueous solutions significantly less than other polymeric materials. The smallest among regenerated cellulose. Therefore, the formation of a cake layer on the surface of the hollow fibers due to adsorption can be almost completely prevented with ammonium ammonium cellulose, and it is also possible to suppress the decrease in the filtration rate of the hollow fibers over time.

The porous hollow fibers of the present invention have little effect in removing viruses from an aqueous solution by utilizing adsorption action. In addition, antigen is generally filtered out in the filtrate.

Although it is a regenerated cellulose, ammonium ammonium cellulose porous hollow fibers have excellent mechanical properties. It also has high parentage,
Suitable for filtration of aqueous solutions.

There are various methods for producing regenerated cellulose, such as the viscose method, the saponification method of cellulose esters, and the copper ammonia method, but due to the differences in the production methods, the physical and chemical properties of each method are different from that of regenerated cellulose. -This is not something to be discussed legally.

In the copper ammonium method, the acid treatment essential for regeneration causes the generation of fine pores and a unique aggregated structure of molecular chains due to the removal of copper. It shows peculiar behavior in sex.

The viscosity average molecular weight of regenerated cellulose is 10 x 10'
The above is preferable. As the viscosity average molecular weight decreases, the amount of components dissolved into the solution or decomposed products eluted from the hollow fibers increases. Furthermore, as the molecular weight decreases, mechanical properties also decrease, which is undesirable.

Since the present invention is mainly used in the biochemical industry and the pharmaceutical industry, it is not preferable that substances other than the target substance be dissolved or dispersed in the obtained filtrate.

The amount of dissolved matter from such copper ammonium cellulose is NaOH
There is a positive correlation with the amount dissolved in an aqueous solution. As a hollow fiber for virus removal, use 0.1 N N at 40℃ for 48 hours.
When immersed in an aOH aqueous solution, it is desirable that the dissolved components be 0.1% or less. In order to produce hollow fibers that satisfy this condition, regenerated cellulose using the copper ammonia method is produced using a raw material made of high-purity cellulose, or after the hollow fibers are produced, they are washed with a 0.1 N NaOH aqueous solution for at least 72 hours. Just process it. It is more preferable to use a high-purity cellulose raw material because the above-mentioned dissolved components are significantly reduced. Here, high-purity cellulose raw material has an α-cellulose content of 95%.
It refers to cotton linters, wood bulbs, etc. with a degree of polymerization of 700 or more in weight percent or more. It is preferable to always use purified water to prevent decomposition and oxidation of these raw materials during bleaching and washing steps, and to avoid contamination with impurities.

The combination of defined membrane structure and defined pore properties is particularly important for increasing the virus inhibition rate. That is, the average pore diameter according to the water filtration rate method is 10 to 10,001
I, the in-plane porosity (Pre) is 0.25 or more, the hollow fiber has a layered structure with 10 or more layers in the wall thickness direction, and the minimum average pore diameter is 0.02 to 0.2 μ- The minimum in-plane porosity (Pre') is 0.05 to 0.5. Here, hollow fibers with a layered structure in the wall thickness direction are: ■ have a homogeneous structure in a plane parallel to the outer or inner wall surface, ■ have a certain pore size distribution and average pore size, Pre defined in each layer, and ■
For surfaces with different distances from the membrane surface, the pore size distribution, average pore size, and Pr.

Both change depending on the distance from the membrane surface, and (1) means that it has a homogeneous structure in both directions parallel to the membrane surface. A homogeneous structure is a structure in which the pores are arranged randomly, and when the average pore diameter is measured at any two locations using an electron microscope, the average pore diameter of the third order calculated by equation (2) below, This means that the difference in the values of the two values agrees within 20% as a relative value.

In addition, the structure of the cross section perpendicular to the membrane surface has a diameter of 0.1 to 2 μm.
(the particle diameter is assumed to be 2S). The number of layers referred to in the present invention is T/4 where the wall thickness is T.
It is defined by S. In addition, the minimum average pore diameter means the minimum value of the distance dependence of 2r'+ in the film thickness direction, and the minimum in-plane porosity Pre' means the minimum value of the distance dependence of Pre in the film thickness direction. means.

As the average pore size increases, the filtration rate increases. Therefore, the larger the average pore diameter, the more desirable it is in terms of workability. However, as the average pore size increases, the virus concentration in the filtrate increases, becoming 1/1 of the virus concentration in the stock solution.
It is impossible to make it less than 0'. These general trends are also observed in the present invention. However, the hollow fiber of the present invention has extremely high virus removal efficiency. This removal efficiency decreases rapidly when the number of layers is less than 10. Number of layers is 1
If the layer is 0 or more, for example, even if the minimum average pore diameter is 1.1 times or more the diameter of the virus to be removed, the virus concentration in the filtrate will be 1/10' or less of that in the stock solution.

The larger the number of layers, the larger the average pore diameter and minimum average pore diameter determined by the water filtration rate method, and the above virus removal ability is maintained. However, if the minimum average pore diameter exceeds four times the diameter of the virus to be removed, the above virus removal ability cannot be achieved even if the number of layers is 100. As the number of layers increases, the filtration rate decreases, so the number of layers cannot be increased significantly. When a specific virus to be separated is identified, it is preferable to perform filtration with a minimum average pore size of 4 times or less the virus diameter. Furthermore, in order to further increase the virus removal ability under certain conditions with respect to the number of layers and the ratio of the virus diameter to the minimum average pore diameter, the minimum average pore diameter must be 0.2 μm or less and Pre' must be 0.5 or less. It is. In order to maintain a high filtration rate, the average pore diameter in the water filtration rate method should be Lone or more.
Minimum average pore diameter is 20 nm or more and Pre” is 0.05
It is necessary that it is above.

Generally, as Pre' increases, virus removal ability decreases. Therefore, it is preferable to select an appropriate combination of Pre' and T. For example, the minimum in-plane porosity Pre and T
Pre'/T is preferably 0.002 or more and 0.02 or less. It was believed that the thinner the wall thickness T is in conventional asymmetric membranes, the better.
0'' or less requires a T of 10 µm or more. Also, in relation to mechanical properties, the larger the T, the better. However, if the T is thicker (the amount of protein adsorbed will increase). , or the filtration rate is reduced.

The wall thickness was set at 100 μm because it can fully function as a layered structure and because it is easy to manufacture a layered structure.
It is preferable that it is below.

The features of the present invention, that is, high virus inhibition rate, high filtration rate, high protein concentration in the filtrate, and little change in filtration characteristics over time, are better exhibited by providing a specific porous membrane shape. That is, the present invention has a hollow fiber shape having a circular cross section with an inner diameter of 200 to 800 μm, and a wall thickness T (expressed in μm) of 20 μm to 100 μm.
Preferably, it is designed to have a continuous penetration in μm and a length of 5 to 50 c+++. These specified shapes can prevent denaturation of coexisting proteins during ultrafiltration of viruses. This is probably because there is a correlation between the denaturation of proteins and the rate of friction applied to the solution before filtration, the smoothness of the flow (streamline) of the solution, and the local rate of friction when passing through the pores. It will be done. Proteins are also present in the virus-containing solution, so the viscosity of the solution increases with filtration time. Increase the length of the hollow fiber,
Furthermore, as the inner diameter becomes smaller, it is necessary to increase the pressure applied to the hollow fibers. Increasing the inner diameter will reduce protein denaturation, but the loadable pressure will rapidly decrease, the amount of solution remaining inside the hollow fiber will increase, and the size of the filtration device with the same effective area will increase. Therefore, it is preferable to design the inner diameter to 200 to 800 μm. The length of the hollow fiber should be varied depending on the inner diameter, but for the above inner diameter range, an effective length of 5 to 50 am is suitable.

Under conditions of specified inner diameter and film thickness, as Pre' increases, the mechanical properties of the hollow fiber decrease. In order to increase the ultrafiltration rate and maintain a high virus inhibition ability, Pre
The optimum range of ' is preferably 0.15 or more and 0.45 or less. Under these conditions, it is desirable to design the mechanical properties of the hollow fibers within a range that is sufficiently practical even under water.

Furthermore, in ammonium-produced cellulose, if the degree of orientation of the cellulose molecular chains is low, dimensional changes occur in water, which is undesirable. In order to simultaneously satisfy these preferable requirements, the degree of orientation of cellulose molecular chains must be 60% or more, and the viscosity average molecular weight must be 10%.
If it's more than 10,000, you can almost reach your goal.

In the process of spinning hollow fibers using a cuprate-ammonia solution with a cellulose concentration of 3 to 10% by weight as a spinning stock solution, microphase separation occurs slowly from the inner and outer wall surfaces toward the inside, and simultaneously within the same plane. It is made by proceeding. The winding speed is set so that the hollow fibers are immersed in the coagulation solution for one minute or more.

At this time, it is necessary to strictly control the temperature of the stock solution, hollow agent, and coagulant. Hollow fibers having the same structure as the present invention can also be obtained when only the inner and outer wall surfaces are made of natural cellulose biosynthesized using acetic acid bacteria or the like. Here, microphase separation means a state in which a concentrated layer or a dilute phase of polymers is dispersed and stabilized as particles with a diameter of 0.02 to several μm in a solution. The occurrence of microphase separation can be confirmed by direct visual observation of the devitrification phenomenon of the fibers during the spinning process, or by electron microscopic observation of the fibers after spinning, based on the presence of particles with a diameter of 0.02 to several μm.

In order to remove hepatitis B virus in plasma, for example, the average pore diameter measured by the water filtration rate method is 20 to 40,171) and the in-plane porosity is 0.20 to 0.50. Minimum average pore diameter is 0.
Copper ammonium regenerated cellulose having a thickness of 0.4 to 0.10 μm, a film thickness of 20 μm, and 10 or more layers in the wall thickness direction may be used.

Prior to a detailed explanation of the present invention, the definitions and measurement methods of each technical term (physical property value) used in this specification are shown below.

After embedding the hollow fibers with extremely small average pore diameter and extremely small in-plane porosity in acrylic resin, an ultra microtome (Ultra Dome Ul manufactured by LKB (Sweden)) was used.
Using a glass knife attached to a Tra Come [8800 model], ultrathin pieces with a thickness of about 1 μm are cut out at various positions from the inner wall surface to the outer wall surface of the hollow fiber parallel to the fiber axis direction. An electron micrograph of the sample section is taken. Each sample section is at a different distance from the inner wall. The number of holes whose hole radius is r-wrtdr per 1 ctA of the section of interest is expressed as N (r) dr. The average pore radius T3 and in-plane porosity Pre are each +21.
(Given by equation 31.

r3 and Pre are measured as a function of distance from the inner wall surface, and their minimum values are defined as r*' and Pre'.

2rz'' is the minimum average pore diameter, and Pre'' corresponds to the minimum in-plane porosity.

A porous hollow fiber module made of regenerated cellulose with an average pore diameter was prepared using the water filtration rate method, and the water filtration rate Q (d/
The average pore diameter was calculated by substituting the measured value (minute) into equation 4).

d: Wall thickness (μm), ΔP: Wall pressure difference (mmtlg)
+A: Effective filtration area of module (m) Pre: Porosity (-) μ: Viscosity of water (centipoise) Pre is the apparent density when swollen with water, ρaW, and the density of cellulose solid is 1.56 g/-. Expenditures were calculated using equation (5).

Pr p = (1-p aw/ 1.56) (
5) Virus concentration E. coli phage φX174 (IFO20009, host E. coli IF013898. Virus diameter 25 nm) and E. coli phage T 4 (IFO20004, host E. coli IF013168. Virus diameter 85 nm) were infected on a soft agar medium for 12 to 24 days. time 3
Cultured at 7°C. Soft agar 20- to E. coli culture medium 5-
The mixture was collected, and after adding 0.1 ml of chloroform, the mixture was kept at 37° C. for 15 minutes, and centrifuged at IIIOORPM for 10 minutes to obtain a supernatant.

This supernatant liquid was filtered through a millibore filter (Millex GV).
) was aseptically filtered. The obtained filtrate was used as a virus stock solution. Virus concentrations in the virus stock solution and filtrate were determined by plaque formation. If the titers of the stock solution and filtrate are No and N, respectively, the virus inhibition coefficient Φ is (
6) Defined by Eq.

φ=l! og No./N (61 Degree of orientation of molecular chains) Rigaku Denki's xvA generator Rυ-200PL, Goniometer 5G-9R, and scintillation counter are used.

CaKα rays (wavelength: 0.1542 nm) generated at a tube voltage of 30 kV and a tube current of 80 mA were made monochromatic with a nickel filter, and X'+fA was used as the incident X-ray. Hollow fibers are bundled to a diameter of approximately 2N and the diffraction angle 2θ = 20.2 degrees ((101)
The azimuthal dependence of the X-ray intensity (reflection from surfaces) was measured by a symmetrical transmission method (scanning speed 4°/min, chart speed 10+nm/min, collimator diameter 2 mmφ). The average value of the X-ray intensity at the azimuth angle ±90' (corresponding to the meridian) is taken as the baseline, and the peak value of the X-ray diffraction intensity is 17
The angular width (half width) H (in degrees) indicating the value of 2 is measured on the chart. The degree of orientation of the molecular chain is given by 8O-H x 100 (%).

〔Effect of the invention〕

The hollow fibers of the present invention make it possible to reduce the concentration of viruses dispersed in an aqueous solution to 1/10' or less of the concentration of the original solution. At this time, the antigen concentration is 5% of that of the filter agent.
That's all. Furthermore, even when proteins coexist, the total protein concentration in the filtrate is maintained at 80% or more of that in the stock solution, and the biological activity of the protein hardly decreases. Furthermore, the filtration rate is higher than that of a known porous membrane with an average pore diameter of 4 and the same membrane thickness. Of course, with known porous membranes, the virus concentration in the filtrate is 1/10' or more of that in the stock solution, and the filtration rate decreases significantly over time. Furthermore, since the hollow fibers of the present invention have a small adsorption amount of proteins in aqueous solutions (particularly in physiological saline or plasma), the reduction in filtration rate when removing viruses from aqueous solutions containing proteins is significantly small. .

Examples and Comparative Examples Cellulose link (α-cellulose content 196% or more 1 average molecule ffi 2.6×10′) was dissolved in a copper ammonia solution prepared by a known method at various concentrations of 4 to 10% by weight, Filtration and defoaming were performed to obtain a spinning stock solution. While controlling this stock solution at a constant temperature of 25.0°C ± 0.1°C, a 1.9° C.
Discharged at ml/min. On the other hand, acetone 44 as a hollow agent
A mixed solution of 0.60% by weight of ammonia and 55.40% by weight of water at 22.0°C ± 0.1°C was added to the central spinning outlet (
It was discharged in the falling direction at 2.2 d/min from the outside diameter of 0.6 mmφ). The discharged liquid was a mixed solution (25% by weight) of 44% by weight of acetone, 0.58% by weight of ammonia, and 55.42% by weight of water.
, 0°C ± 0.1°C) and wound up at a speed of 3 to 6 m/min. The transparent blue fibers immediately after discharge gradually became white as the spinning process progressed, and it was observed with the naked eye that microphase separation was occurring. After that, coagulation progresses, and in the winding process, it becomes a blue-white hollow fiber in the form of a fiber. This hollow fiber is immersed in a fixed length in acetone/water (50150 weight ratio) at 20''C for 1 hour.

After that, it is regenerated into cellulose with a 2% by weight sulfuric acid aqueous solution,
It was then washed with water. The water-washed hollow fibers were immersed in an acetone solution, and after the solvent was replaced with water and acetone, the acetone inside the hollow fibers was removed by air drying while being stretched by about 10%.

Table 1 shows the structural properties of the hollow fibers obtained.

(Left below) Table 1: Cellulose) Purchasing properties of porous hollow W obtained by varying the seismic intensity 500 of each of these hollow fibers,
It was bundled to a length of 1 Q cm and molded into a cylindrical module. The module is steam sterilized before filtration use and then PB
The inside of the hollow fiber was washed with S. A stock solution containing a virus was injected into the hollow fiber, and the stock solution was filtered under a constant pressure of 200 mmHg in an almost stationary state. φ× as a virus
174, Samples A, B, C, and D correspond to Examples, and Samples E and F correspond to Comparative Examples. When T4 is used as the virus, samples C, D, E,
Case F is an example and is sample A.

B corresponds to a comparative example. The inhibition coefficient Φ and filtration rate calculated from the virus concentration in the obtained filtrate are summarized,
Table 2 shows Examples, and Table 3 shows Comparative Examples.

Table 2 Example A φX174 6.6 >8.8B
φX174 17.0 >8. O.C.
φX 174 45.0 6. OD,
φX 174 89.0 4. OCT4
42.0 >8.0D T4
83.0 >8.0E T4
149 7.0F T4 27
2 6.0 Table 3 Comparative Example E φX174 170 2.5F
φX174 300 1. OA
T4 4.6 >8. OB
T4 13.9 > 8.0 In the combination of sample E/φ×174 and sample F/φ×174 of the comparative example, Φ is 4 or less, and in the comparative example sample A/T4 and sample B/T4, the filtration rate is Example sample F/T4
It is 1720 or less in the case of the combination.

Claims (4)

[Claims] (1) Made of regenerated cellulose, with an average pore diameter of 10 to 100 nm by water filtration rate method, and an in-plane porosity (Pre) of 0.
．． 25 or more, a minimum average pore diameter of 0.02 to 0.2 μm, a minimum in-plane porosity (Pre') of 0.05 to 0.5, and a layered structure having 10 or more layers in the wall thickness direction. A porous hollow fiber for separating and removing viruses, characterized in that the wall thickness (T, expressed in μm) of the hollow fiber is 10 μm or more. (2) Made of cellulose regenerated by copper ammonia method, Pre
The relationship of equation (1) holds between ' and T, and 0.002≦
Pre′/T≦0.02 (1) and when the hollow fiber was immersed in a 0.1N NaOH aqueous solution at 40°C for 48 hours,
The porous hollow fiber for virus separation and removal according to claim 1, wherein the dissolved component from the hollow fiber is 0.1% or less. (3) Minimum in-plane porosity is 0.15 or more and 0.45 or less, and the degree of orientation of cellulose molecular chains constituting the hollow fiber is 6
0% or more, and the viscosity average molecular weight of cellulose molecules is 10×10^4 or more. The porous hollow fiber for separating and removing viruses according to claim 1 or 2. (4) Made of cellulose regenerated by the cuprammonium method, the average pore size is 20 to 40 μm, Pre is 0.20 to 0.50, the minimum average pore size is 0.04 to 0.10 μm, and the film thickness is 20 μm or more. A porous hollow fiber for separating and removing hepatitis B virus according to claim 3.