Fiber bundle, its manufacturing method and purification column

Abstract

The present invention addresses the problem of providing a small purification column that has a reduced treated liquid capacity but still achieves low pressure loss and has high adsorptivity. The present invention is a fiber bundle that includes a plurality of porous fibers and satisfies conditions (A)–(E). (A) The porous fibers have a solid shape. (B) The arithmetic average roughness (the dry Ra value) of the surface of the porous fibers when dry is 11–30 nm. (C) The arithmetic average roughness (the wet Ra value) of the surface of the porous fibers when wet is 12–40 nm. (D) The value of the wet Ra value / the dry Ra value is at least 1.05. (E) The linearity of the fiber bundle as represented by (the length of the fiber bundle) / (the length of one porous fiber) is 0.97–1.00.

Description

[Technical field]

[0001] The present invention relates to a fiber bundle used for removing adsorbed substances from a liquid to be treated by adsorption, a method for producing the same, and a purification column. [Background technology]

[0002] Purification columns used to remove adsorbed substances from a liquid to be treated by adsorption are used in a wide range of fields. In particular, in the medical field, they are used in blood purification therapy, in which the liquid to be treated, such as blood, is taken out of the body, and disease-causing substances and the like in the liquid are removed through a purification column, purified, and then returned. The purification column used here is sometimes called a blood purification column. The advantage of these blood purification therapies is that they have fewer side effects compared to treatment methods in which drugs are administered directly into the patient's body. On the other hand, when a large amount of blood is taken out of the body, there is a risk of causing side effects such as a drop in blood pressure and anemia, so it is necessary to minimize the amount of the patient's blood taken out of the body (also called the "amount of blood taken out") as much as possible.

[0003] In order to reduce the amount of blood taken out, it is necessary to reduce the size of the purification column, but simply reducing the size of the column reduces the efficiency of blood purification.

[0004] Therefore, efforts have been made to develop adsorbents and columns that aim to reduce the amount of liquid to be treated while achieving high adsorption performance.

[0005] For example, Patent Document 1 describes an invention regarding a column that uses beads as an adsorbent.

[0006] Patent Document 2 describes a column in which fibers are packed and arranged.

[0007] Patent Document 3 describes that by using solid fibers as the adsorbent and designing and optimizing the column, the residue of the treated liquid (residual blood in the case of blood) can be suppressed and the adsorption performance of the adsorbed substance can be improved.

[0008] Patent Document 4 discloses a blood purification membrane in which the center surface average roughness of the blood contact surface in a wet state is less than a certain value. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] JP 2016-215156 A [Patent Document 2] JP 2009-29722 A [Patent Document 3] JP 2017-185221 A [Patent Document 4] JP 2005-224604 A [Non-patent literature]

[0010] [Non-Patent Document 1] Kazuhiko Ishikiriyama et al.; JOURNAL OF COLLOID AND INTERFACE SCIENCE, 171, 103-111, (1995) [Non-Patent Document 2] Kazuhiko Ishikiriyama et al.; JOURNAL OF COLLOID AND INTERFACE SCIENCE, 173, 419-428, (1995) [Non-Patent Document 3] Abstracts of the 38th Pore Diameter Calorimetry Symposium 38-39 Summary of the Invention [Problem to be solved by the invention]

[0011] When reducing the size of a column, if only the length of the column is reduced, the liquid to be treated will not come into uniform contact with the adsorbent packed in the column, and there is a risk of short-path formation in which the liquid to be treated flows only near the center of the axis. On the other hand, if only the cross-sectional area of ​​the column is reduced, the pressure on the liquid to be treated entering the column will increase, and the pressure on the liquid to be treated leaving the column will decrease. In the process of this pressure loss, particularly when the liquid to be treated is blood, the high pressure stimulates and activates the blood cell components, damaging them and causing hemolysis.

[0012] For this reason, in order to realize a uniform flow of the liquid to be treated within the column and to suppress an increase in pressure loss, it is necessary to reduce both the cross-sectional area and the length of the column.

[0013] However, in the prior art disclosed in Patent Documents 1 to 3, when attempting to prepare a low-capacity purification column for treating a small amount of liquid, there were the following difficulties in obtaining a purification column with excellent adsorption performance while suppressing pressure loss.

[0014] In Patent Document 1, when the adsorbent is in the form of beads, the surface area per unit volume of the adsorbent is minimized due to its spherical shape, and if the bead diameter is reduced or the amount of beads packed is increased in order to increase the surface area per unit volume, the gaps between the beads will become narrower, which may increase the pressure loss.

[0015] In Patent Document 2, beads, hollow fibers, and solid fibers are described as adsorbents, but there is a problem in ensuring the surface area that contributes to adsorption. In addition, it is possible to increase the total surface area that contributes to adsorption by increasing the number of packed fibers by reducing the diameter of the fibers, but in this case, the gaps between the adsorbents become narrower, increasing the flow resistance. The pressure loss increases with the increase in flow resistance. Therefore, there is still a problem in achieving both low pressure loss and high adsorption performance when reducing the size of the column.

[0016] Patent Document 3 describes that it is possible to improve flow properties and reduce pressure loss by suppressing the meandering of the fibers contained in the fiber bundle. However, the pressure loss in the examples is also relatively high, and if the column is downsized as it is, it is thought that it will be difficult to achieve both high adsorption performance and low pressure loss.

[0017] Patent Document 4 relates to a separation membrane, which does not achieve both adsorption and inhibition of hemolysis caused by stimulation of blood cell components.

[0018] Therefore, an object of the present invention is to provide a purification column which is small in size and has a reduced volume of treated liquid in order to reduce the amount of blood taken out, yet which achieves low pressure drop and has high adsorption performance. [Means for solving the problem]

[0019] That is, the present invention provides a fiber bundle containing a plurality of porous fibers that satisfies the following requirements (A) to (E) (fiber bundle (I) of the present invention). (A) The porous fiber has a solid shape. (B) The arithmetic mean roughness (dry Ra value) of the surface of the porous fiber in a dry state is 11 nm or more and 30 nm or less. (C) The arithmetic mean roughness (wet Ra value) of the surface of the porous fiber in a wet state is 12 nm or more and 40 nm or less. (D) The value expressed as wet Ra / dry Ra is 1.05 or more. (E) The linearity of the fiber bundle, expressed as (length of fiber bundle) / (length of one porous fiber), is 0.97 or more and 1.00 or less.

[0020] The present invention also relates to a purification column in which the fiber bundle of the present invention is housed approximately parallel to the longitudinal direction of a cylindrical case, and headers having an inlet port and an outlet port for the liquid to be treated are attached to both ends of the cylindrical case (purification column (I) of the present invention).

[0021] The present invention also relates to a purification column in which a fiber bundle formed by bundling two or more fibers is housed approximately parallel to the longitudinal direction of a cylindrical case, and headers having an inlet port and an outlet port for the liquid to be treated are attached to both ends of the cylindrical case, and which satisfies the following requirements (i) to (v) (purification column (II) of the present invention): (i) In the cross section of the fiber, the diameter of the inscribed circle is Di and the diameter of the circumscribed circle is Do, and the irregularity of the cross section of the fiber, expressed as Do / Di, is 1.3 or more and 8.5 or less. (ii) The filling rate of the fiber in the storage portion is within the range of 40% to 73%. (iii) The inner diameter of the housing is 32 mm or more and 60 mm or less. (iv) The linearity of the fiber, expressed as (the length of the fiber bundle contained in the purification column) / (the length of one fiber contained in the purification column), is 0.97 or more and 1.00 or less. (v) The capacity of the flow path for the liquid to be treated in the storage unit is within the range of 5 mL to 60 mL.

[0022] The present invention also provides a method for producing a fiber bundle, which comprises bundling the fibers under conditions that satisfy the following (a) and (b): (a) The tension when the fiber is wound onto a skein is 0.5 gf / skein or more and 10.0 gf / skein or less. (b) During one rotation of the skein, the traverse movement distance (the distance traveled parallel to the direction perpendicular to the traveling direction of the fiber) is 0.1 mm or more and 30 mm or less. Effect of the Invention

[0023] According to the present invention, it is possible to obtain a purification column that is small in size and has a reduced volume of the liquid to be treated in order to reduce the amount of blood taken out, while realizing low pressure loss and having high adsorption performance. [Brief description of the drawings]

[0024] [Figure 1] FIG. 2 is a side view illustrating one embodiment of a purification column according to the present invention. [Diagram 2]FIG. 2 is a circuit diagram for measuring β2-MG clearance using a purification column according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] The present invention will be described in detail below. In the present invention, the term "not less than" means that the value is the same as or larger than the indicated value, and the term "not more than" means that the value is the same as or smaller than the indicated value. Furthermore, when there is no particular distinction between "fiber bundle (I) of the present invention" and "purification column (II) of the present invention," such as "fiber in the present invention," the term applies to both.

[0026] <Textile> The material constituting the fiber in the present invention is not particularly limited, but polymeric materials are preferably used from the viewpoint of ease of molding and cost, for example, polymethyl methacrylate (hereinafter referred to as PMMA), polyacrylonitrile (hereinafter referred to as PAN), polysulfone, polyethersulfone, polyarylethersulfone, polypropylene, polystyrene, polycarbonate, polylactic acid, polyethylene terephthalate, cellulose, cellulose triacetate, ethylene-vinyl alcohol copolymer, polycaprolactam, etc. are used. In addition, when it is made into a fiber, it is preferable to include a material having a property of being able to adsorb proteins and the like by hydrophobic interaction, for example, PMMA, PAN, etc. When it is made into a fiber, it is preferably used because it has a homogeneous structure, the pore size distribution is easy to control, and relatively sharp material separation is possible. Furthermore, since amorphous polymers do not crystallize in the spinning process and subsequent processes, they have excellent spinnability, continuous productivity, and processing moldability. In particular, PMMA is an amorphous polymer and has high transparency, so that the internal state of the fiber is relatively easy to observe, and it is preferable because it is easy to evaluate the perfusion state of the treated liquid, such as fouling.

[0027] In addition, the surface of the fiber may be modified for the purpose of improving the adsorption performance of the adsorbed substance by controlling the ligand or charge state, and controlling the surface properties such as friction and biocompatibility of the membrane by polymers and functional groups. Modification refers to immobilizing a polymer or a low molecular weight compound on the membrane surface. Here, the immobilization state is not particularly limited, and may be chemically bonded or may be physically bonded such as electrostatic interaction or hydrogen bond. The modification method is not particularly limited, but for example, a modified fiber with a hydrophilic polymer immobilized on the surface can be obtained by irradiating the fiber in a state where the fiber is in contact with an aqueous solution containing a polymer. When a purification column is used for applications such as medical equipment, sterilization can also be achieved by irradiating the fiber with radiation.

[0028] In addition, the fiber in the present invention preferably has a porous structure having pores inside the fiber. In addition, the fiber in the fiber bundle (I) of the present invention has a porous structure having pores inside the fiber. By making it a porous structure, the adsorbed substance can be adsorbed not only on the fiber surface but also in the pores inside the fiber, improving the adsorption performance per volume.

[0029] The average pore radius of the fiber is preferably 0.8 nm or more, more preferably 1.5 nm or more, even more preferably 2.0 nm or more, and even more preferably 2.5 nm or more. On the other hand, it is preferably 90 nm or less, more preferably 55 nm or less, even more preferably 30 nm or less, and even more preferably 22 nm or less. When the average pore radius is in the above preferred range, the adsorbed substance is not only adsorbed on the fiber surface, but also diffuses and penetrates into the fiber and is adsorbed in the internal pores, improving the adsorption efficiency.

[0030] The average pore size, pore volume, and pore size distribution of the porous fiber can be determined by measuring the freezing point depression caused by capillary coagulation of water in the pores using a differential scanning calorimeter (DSC) capable of measuring in a wet state. Specifically, the adsorbent is quenched to -55°C, then heated to 5°C at a rate of 0.3°C / min, and the measurements are performed, and the values ​​are calculated from the obtained curve. For details, refer to the description in Non-Patent Document 1. The i-th average pore size, i.e., the average pore radius as referred to in the present invention, is determined from the following formula (2) in Non-Patent Document 3 based on formula (1) in Non-Patent Document 2. Here, the primary average pore size is i=1, and this value is the average pore size.

[0031]

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[0032]

number

[0033] The porous fiber in the present invention preferably has an aperture ratio of the openings on the fiber surface, i.e., a surface aperture ratio of 0.1% or more and 30% or less. The surface aperture ratio in the present invention refers to holes or gaps on the surface of the porous fiber, which does not include pores inside the fiber and is classified as a black part by the following measurement method. By making the surface aperture ratio 0.1% or more, more preferably 0.5% or more, even more preferably 1% or more, and even more preferably 2% or more, a flow path to the inside of the fiber can be secured, and the adsorption performance can be improved. In addition, by making it 30% or less, more preferably 25% or less, even more preferably 20% or less, and even more preferably 15% or less, the smooth surface can suppress collisions between components in the blood and the fiber surface during blood processing, and suppress hemolysis.

[0034] The fibers in the present invention preferably have a homogeneous porous structure in the cross-sectional direction. Since the adsorbed substance diffuses into the porous fibers and is also adsorbed into the pores inside the fibers, the homogeneous porous structure contributes to the adsorption efficiency, including the inside of the fibers.

[0035] Here, the homogeneous porous structure refers to a porous structure in which the ratio of the average pore size in the region near the outer surface of the fiber to the average pore size in the central region of the fiber (average pore size in the region near the outer surface / average pore size in the central region) is 0.50 to 3.00 times, preferably 0.75 to 2.00 times, more preferably 0.85 to 1.50 times.

[0036] Next, a method for determining the homogeneous structure in the present invention will be described. First, the porous fiber is sufficiently wetted and then immersed in liquid nitrogen, and the moisture in the pores is instantly frozen by the liquid nitrogen. Then, the porous fiber is quickly folded, and in a state in which the fiber cross section is exposed, the frozen moisture is removed in a vacuum dryer of 0.1 torr (13.3 Pa) or less to obtain a dried sample. Then, a thin film of platinum (Pt) or platinum-palladium (Pt-Pd) is formed on the fiber surface by sputtering to obtain an observation sample. The cross section of the sample is observed with a scanning electron microscope (for example, S-5500 manufactured by Hitachi High-Technologies Corporation). Here, a radius passing through the center point of the fiber cross section is arbitrarily selected, and concentric circles passing through the points dividing the line segment of this radius into five equal lengths are drawn, and the region including the center point is defined as the central region, and the side closest to the outer periphery is defined as the outer surface vicinity region. The circle equivalent diameters of the holes present in each of the central region and the outer surface vicinity region are obtained, and the average pore diameters in each region are obtained. When calculating the average pore size in each region, 20 areas of 2 μm x 2 μm are arbitrarily selected using a scanning electron microscope (50,000x), and the entire pore is measured in the photograph taken to calculate the average pore size. In measuring the pore size, a transparent sheet is placed over the printed electron microscope image, and the pores are filled in black using a black pen or similar. The transparent sheet is then copied onto a blank sheet of paper to clearly distinguish the pores as black and the non-pores as white, and the pore size is calculated using image analysis software.

[0037] In the fiber bundle (I) of the present invention, it is important that the arithmetic mean roughness (dry Ra) of the fiber surface in the dry state of the porous fiber is 11 nm or more and 30 nm or less (requirement (B)). By making the dry Ra 11 nm or more, preferably 12 nm or more, more preferably 13 nm or more, and even more preferably 14 nm or more, unevenness is present on the fiber surface, the flow in the immediate vicinity of the surface is disturbed, the boundary layer between the fiber surface and the substance in the liquid to be treated is thinned, and the adsorption performance can be improved. In addition, by making the dry Ra 30 nm or less, preferably 28 nm or less, more preferably 26 nm or less, and even more preferably 24 nm or less, when the liquid to be treated is blood, the frequency of contact, collision, and abrasion between blood cells and the fiber surface can be suppressed, and the release of hemoglobin inside red blood cells into the blood due to damage and activation of the blood cells (hemolysis) can be suppressed.

[0038] In the fiber of the present invention, the arithmetic mean roughness (wet Ra) of the fiber surface in a wet state is preferably 12 nm or more and 40 nm or less. In addition, in the fiber bundle (I) of the present invention, it is important that the arithmetic mean roughness (wet Ra) of the porous fiber surface in a wet state is 12 nm or more and 40 nm or less (requirement (C)). By making the wet Ra 12 nm or more, preferably 13 nm or more, more preferably 14 nm or more, and even more preferably 15 nm or more, unevenness is present on the fiber surface, the flow in the immediate vicinity of the surface is disturbed, the boundary layer between the fiber surface and the substance in the liquid to be treated is thinned, and the adsorption performance can be improved. In addition, by making it 40 nm or less, preferably 38 nm or less, more preferably 36 nm or less, and even more preferably 34 nm or less, when the liquid to be treated is blood, the frequency of contact, collision, and abrasion between blood cells and the fiber surface can be suppressed, and the release of hemoglobin inside red blood cells into the blood due to damage and activation of the blood cells (hemolysis) can be suppressed.

[0039] In addition, in the fiber bundle (I) of the present invention, it is important that the value obtained by dividing the wet Ra of the porous fiber by the dry Ra is 1.05 or more (requirement (D)). By making the wet Ra / dry Ra 1.05 or more, the molecular chains on the surface of the porous fiber can be made to swell sufficiently when they come into contact with a liquid. This reduces the amount of adhesion of useful plasma proteins such as immunoglobulins, and can suppress undesirable effects such as a decrease in immune function.

[0040] In the present invention, the fibers are preferably solid or hollow. It is also important that the porous fibers in the fiber bundle (I) of the present invention have a solid shape (requirement (A)). In a straw-shaped hollow fiber having a cavity inside the fiber, when a liquid to be treated is passed through the inside and outside of the fiber, a pressure difference occurs between the inside and outside, and the liquid to be treated is retained due to the pressure difference. When the liquid not to be treated is blood, a phenomenon called residual blood may occur, in which blood adheres and remains inside, but solid fibers can prevent this phenomenon.

[0041] The fiber in the present invention preferably has a non-circular cross-sectional shape. The fiber arranged in the purification column (II) of the present invention has a non-circular cross-sectional shape. By forming the fiber into a non-circular cross-sectional shape, the surface area per volume can be increased, and the adsorption performance as a purification column can be improved. The degree of non-circularity of the non-circular cross-section of the fiber can be expressed by the degree of non-circularity. The degree of non-circularity here is the ratio of the diameters of the inscribed circle and the circumscribed circle when observing the fiber cross section, that is, the value represented by the ratio Do / Di of the diameter Di of the inscribed circle and the diameter Do of the circumscribed circle. When a fiber with a non-circular cross-section is adopted, it is possible that the stimulation to blood cells and the like is greater than that of a circular fiber, so it is preferable to apply the fiber bundle (I) of the present invention.

[0042] Here, the irregular cross section may be a shape that maintains symmetry such as line symmetry or point symmetry, or may be asymmetric. When the irregular cross section is judged to maintain approximately line symmetry or point symmetry, the inscribed circle is the largest circle that is inscribed in the line that defines the outline of the fiber in the fiber cross section, and the circumscribed circle is the circle that is circumscribed in the line that defines the outline of the fiber in the fiber cross section.

[0043] On the other hand, when the irregular cross section is judged to have a shape that does not maintain any line symmetry or point symmetry, the inscribed circle and circumscribed circle are defined as follows: The inscribed circle is a circle that is inscribed in the line defining the fiber outline at least two points, exists only inside the fiber, and has the largest possible radius within the range where the circumference of the inscribed circle and the line defining the fiber outline do not intersect. The circumscribed circle is a circle that is circumscribed in the line defining the fiber outline at least two points, exists only outside the fiber cross section, and has the smallest possible radius within the range where the circumference of the circumscribed circle and the fiber outline do not intersect.

[0044] The degree of irregularity Do / Di of the cross section of the fiber in the present invention is preferably 1.3 or more and 8.5 or less. In addition, it is important that the degree of irregularity of the cross section of the fiber in the purification column (II) of the present invention is 1.3 or more and 8.5 or less (requirement (i)). By making the degree of irregularity 1.3 or more, preferably 1.5 or more, more preferably 1.8 or more, and even more preferably 2.0 or more, the surface area per volume can be increased, and the ability of the fiber to adsorb the adsorbed substance can be improved. On the other hand, by making it 8.5 or less, preferably 6.5 or less, more preferably 4.0 or less, and even more preferably 3.7 or less, the breaking strength of the fiber can be maintained and bending or cutting of the convex or protruding parts can be prevented. In addition, when the spinning dope is quickly cooled using gas or liquid during spinning into fibers, if the above-mentioned convex or protruding parts are present in excess, the flow of the wind or liquid is hindered. As a result, the cooling inside the fiber is slow, and unevenness tends to occur in the microstructure such as the fiber shape, pores, and surface openings.

[0045] Examples of the cross-sectional shape of a fiber having two protrusions include ellipse, L-shape, V-shape, etc. When there are three protrusions, the shape is Y-shape, T-shape, etc. When there are four protrusions, the shape is cross, etc. When there are five protrusions, the shape is star, etc. When the fiber in the present invention is formed by rapidly cooling the spinning dope using a gas or liquid, the number of protrusions is appropriately selected so that the uneven portions of the fiber are uniformly cooled and structural unevenness is not generated.

[0046] The fiber bundle used in the present invention may contain at least two types of fibers having different cross-sectional shapes. When such an embodiment is adopted, for example, the protrusions and valleys overlap exactly, preventing excessive adhesion between the fibers as occurs in an uneven shape, and providing an advantage of ensuring a flow path for the liquid to be treated.

[0047] The fiber cross section of the fiber used in the present invention preferably has a circle-equivalent diameter of 10 μm or more and 1000 μm or less. The circle-equivalent diameter refers to the diameter when the cross section of the fiber is converted into a circle. By making the circle-equivalent diameter 10 μm or more, more preferably 20 μm or more, even more preferably 30 μm or more, and even more preferably 40 μm or more, the breaking strength of the fiber can be improved, and the fiber is less likely to break during the spinning process, and a fiber with excellent productivity can be obtained. In addition, since the occurrence of fiber breakage and breakage can be suppressed during the manufacturing process, such as the column insertion process after spinning, the handling is also excellent. Furthermore, the volume per surface area is appropriate, and even if the liquid to be treated is passed through for a certain period of time, there is no risk that the adsorption site will be saturated and the adsorption performance will suddenly decrease. In addition, by making the diameter 1000 μm or less, more preferably 800 μm or less, even more preferably 500 μm or less, and even more preferably 300 μm or less, the cooling efficiency of the fiber discharged in the spinning process can be improved, and the shape of the fiber can be easily maintained, making it easier to maintain the irregularity as designed. Maintaining the degree of irregularity is desirable for the development of favorable adsorption performance.

[0048] When the fiber of the present invention is used for medical purposes, it is preferable that the fiber can adsorb pathogenic proteins such as cytokines, β2-microglobulin (β2-MG), low density lipoproteins, very low density lipoproteins, and apolipoproteins. Representative inflammatory cytokines include tumor necrosis factor α (TNFα). TNFα is a protein related to autoimmunity, and its blood concentration increases in rheumatism and the like, causing inflammation, pain, and the like, so it is preferable to remove it from the blood. The TNFα adsorption performance of the fiber of the present invention is preferably 1 μg / cm. 3 More preferably, 15 μg / cm 3 More preferably, 30 μg / cm3 More preferably, 55 μg / cm 3 More preferably, 80 μg / cm 3 That's all.

[0049] On the other hand, it is preferable that the fiber of the present invention has a low adsorption amount for useful proteins such as immunoglobulins and complements. In particular, it is preferable that IgG, which plays a major role in immunity, is not excessively adsorbed. If the amount of IgG adsorbed is too large, it tends to cause a decrease in the immune function of the subject when used as a purification column. Therefore, the IgG adsorption performance of the fiber of the present invention is preferably 13 mg / cm. 3 Less than 9 mg / cm, more preferably 3 More preferably, 6 mg / cm 3 More preferably, 3 mg / cm 3 The following is the result.

[0050] <Fiber bundle> The fiber bundle in the present invention is preferably made of a multifilament consisting of at least a plurality of fibers, at least two or more, as described above. Here, the number of fibers contained in the fiber bundle is appropriately selected based on the shape of the cylindrical case, the packing rate, the fiber diameter, and ease of arrangement. By setting the number within an appropriate range, it is possible to prevent breakage and meandering due to bending and bending of the fibers and contact between the fibers in the manufacturing process after insertion into the cylindrical case. In addition, if the number of fibers is too large, it is not preferable because it becomes difficult to insert the fiber bundle into the cylindrical case and the flow of the liquid to be treated during actual use becomes worse.

[0051] In the case of a multifilament, multiple fibers may be twisted together, but it is preferable not to twist the fibers because the parts where the fibers are in close contact with each other are less likely to come into contact with the liquid to be treated and there is a high possibility that a fiber surface that does not contribute to adsorption will be produced.

[0052] It is important that the fiber bundle used in the present invention has a linearity of 0.97 or more and 1.00 or less, expressed as (length of fiber bundle) / (length of one fiber) (requirements (E), (iv)). By making the linearity of the fiber bundle 0.97 or more, preferably 0.975 or more, more preferably 0.98 or more, and even more preferably 0.99 or more, the situation in which the fibers are arranged in the fiber bundle with an inclination relative to the longitudinal direction of the fiber bundle can be reduced, and pressure loss during columnization and collision of blood cells with the fiber surface can be suppressed, and blood return properties can be improved. The upper limit of the linearity is when the length of the fiber bundle is equal to the length of one fiber, that is, 1.00.

[0053] Here, the "length of the fiber bundle" in the definition of the linearity refers to the length from one end of the fiber bundle to the other end. The "length of the fiber bundle" in the present invention can be obtained by measuring from one end of the fiber bundle to the other end with a vernier caliper at 10 points while uniformly shifting the measurement points in the circumferential direction of the end face of the fiber bundle, and calculating the average value.

[0054] The term "length of one fiber" refers to the length of one fiber measured when one fiber is taken out of a fiber bundle, and is the average value measured for 100 random fibers.

[0055] One issue with purification columns using fiber bundles is adhesion between the fibers, which prevents the treated liquid from properly flowing through the gaps between the fibers, resulting in problems such as short-pass and retention of the treated liquid within the column.

[0056] Up until now, there have been purification columns using fiber bundles, such as artificial kidneys using hollow fiber membranes, but these have been prevented by wrapping spacer fibers around the outer surface of the main fibers in addition to the fibers having the main function, or by imparting crimps to the fibers themselves to prevent adhesion between the main fibers. These methods are suitable for cases where it is necessary to flow the liquid to be treated while retaining it to a certain extent in order to exchange substances by concentration diffusion between the inside and outside of the hollow fiber membrane, which is a function expected of the hollow fiber membrane.

[0057] On the other hand, in a purification column of the type that uses solid fibers and removes adsorbed substances solely by adsorption, as in a preferred embodiment of the present invention, it is more important to ensure an adsorption area of ​​the fibers that can capture the adsorbed substances.

[0058] As described above, the present inventors have intensively investigated a method for preventing adhesion between fibers and ensuring an adsorption area without using spacer fibers, crimping fibers, etc., and have found that it is important to ensure the linearity of each fiber. The importance of this linearity is not merely a theoretical concept, but was discovered for the first time by specifically measuring the length of the fiber bundle and each individual fiber.

[0059] Furthermore, it is expected that the linearity can be maintained more effectively by forming the fibers used in the present invention into a modified cross section.

[0060] As described above, in conventional purification columns, the linearity of each fiber is not taken into consideration, and it can be said that the present invention is a new means of achieving this, which was established by the inventors for the first time. Furthermore, the inventors were the first to discover, through the above-mentioned measurement method, that it is important that the linearity is 0.97 or more and 1.00 or less.

[0061] <Purification column> The fiber bundle in the present invention is used by being accommodated in a column having a cylindrical case with headers attached to both ends. Here, the accommodation section refers to a volume section defined by the inner space of the cylindrical case. A part of the fiber bundle may extend from the end of the accommodation section toward the section defined by the inner space of the header.

[0062] In the purification column of the present invention, the fiber bundle is housed in a cylindrical case in a substantially parallel manner. The term "substantially parallel" means that the fiber bundle is preferably parallel to the longitudinal direction of the cylindrical case, but preferably has a number of fibers with an inclination of 20 degrees or less relative to the longitudinal direction of the cylindrical case of 90% or more of the total. In addition, the fiber bundle may contain some fibers with an inclination of up to 45 degrees at the outer periphery, but it is preferable that the number of fibers with an inclination of more than 20 degrees and 45 degrees or less relative to the longitudinal direction of the cylindrical case is 10% or less of the total. The shape of the fiber in the longitudinal direction when it is incorporated in the column may be a straight shape, a crimped shape, a spiral shape, etc., but a straight shape is preferable. Straight-shaped fibers make it easy to secure a flow path for the liquid to be treated, and therefore it is easy to distribute the liquid to be treated evenly within the column. In addition, the flow path resistance can be suppressed, and even if a solute in the liquid to be treated adheres, a sudden increase in pressure loss can be suppressed.

[0063] The shape of the case constituting the column is preferably a cylinder with both ends open. Therefore, it is preferable that the fiber bundle is housed in a cylindrical case. In particular, a cylinder with a perfectly circular cross section is preferable. This is because the cylindrical case has no corners, which can prevent the liquid to be treated from stagnating at the corners.

[0064] In addition, the cylindrical case is preferably made of plastic, metal, or the like. Among them, plastic is preferably used from the viewpoints of cost, moldability, weight, blood compatibility, and the like. In the case of plastic, for example, a thermoplastic resin excellent in mechanical strength and thermal stability is used. Specific examples of such thermoplastic resins include polycarbonate resins, cellulose resins, polyester resins, polyarylate resins, polyimide resins, ring polysulfone resins, polyethersulfone resins, polyolefin resins, polystyrene resins, polyvinyl alcohol resins, and mixtures thereof. Among these, polypropylene, polystyrene, polycarbonate, and their derivatives are preferable in terms of moldability and radiation resistance required for the cylindrical case. In particular, resins with excellent transparency such as polystyrene and polycarbonate are convenient for ensuring safety, for example, when the liquid to be treated is blood, because the state of the inside can be confirmed during perfusion, and resins with excellent radiation resistance are preferable when radioactive irradiation is performed during sterilization. The resin is processed into a cylindrical case by injection molding using a mold or by cutting the material.

[0065] The inner diameter of the storage section in the purification column of the present invention is preferably 32 mm or more and 60 mm or less. In addition, it is important that the inner diameter of the storage section in the purification column (II) of the present invention is 32 mm or more and 60 mm or less (requirement (iii)). By making the inner diameter of the storage section 32 mm or more, more preferably 34 mm or more, even more preferably 36 mm or more, and even more preferably 38 mm or more, the flow rate per area of ​​the liquid to be treated is reduced, and an excessive increase in pressure loss and the associated hemolysis can be suppressed. In addition, the cylindrical case part can be easily held by the holder during actual use, and it is possible to prevent the cylindrical case part from falling due to insufficient holding, breaking, or cracking. In addition, by making it 60 mm or less, more preferably 58 mm or less, even more preferably 56 mm or less, even more preferably 55 mm or less, and even more preferably 54 mm or less, it is possible to prevent the flow of the liquid to be treated from reaching the outer periphery and the generation of fibers that are not effectively used.

[0066] The length of the storage section in the purification column is preferably 100 mm or more and 1000 mm or less. Here, the length of the storage section refers to the axial length of the cylindrical case before the header is attached. By making it 100 mm or more, more preferably 120 mm or more, even more preferably 140 mm or more, even more preferably 150 mm or more, even more preferably 160 mm or more, the handling property can be improved, the insertion property of the fiber into the column can be improved, and the handling property during the preparation of the column can be improved. On the other hand, by making it 1000 mm or less, more preferably 800 mm or less, even more preferably 600 mm or less, even more preferably 500 mm or less, even more preferably 400 mm or less, the handling property during actual use as a purification column can be made easy.

[0067] In the purification column of the present invention, the length of the fiber bundle / the inner diameter of the storage section (L / D) is preferably 0.5 or more and 2.5 or less. By making it 0.5 or more, more preferably 0.6 or more, even more preferably 0.7 or more, and even more preferably 0.8 or more, it is possible to suppress short-passing at the outer periphery and to improve the ease of handling. On the other hand, by making it 2.5 or less, more preferably 2.0 or less, even more preferably 1.7 or less, and even more preferably 1.4 or less, it is possible to suppress an excessive increase in pressure loss, hemolysis, and increased irritation to blood cells.

[0068] In the purification column of the present invention, the fiber packing rate of the storage section is preferably 40% or more and 73% or less. In the purification column (II) of the present invention, the fiber packing rate of the storage section is 40% or more and 73% or less (requirement (ii)). By setting the packing rate to 40% or more, more preferably 45% or more, even more preferably 50% or more, and even more preferably 55% or more, the fibers in the cylindrical case are less likely to be biased, and it is possible to prevent unevenness in the flow of the liquid to be treated in the purification column. In addition, by setting the packing rate to 73% or less, more preferably 71% or less, even more preferably 70% or less, even more preferably 69% or less, and even more preferably 67% or less, it is possible to improve the insertability into the cylindrical case.

[0069] The filling rate is the capacity of the storage section (Vc) divided by the fiber volume in the storage section (Vf). The capacity of the storage section is the volume of the hollow part of the cylindrical case calculated from the cross-sectional area and length of the storage section. The fiber volume in the storage section is calculated from the fiber cross-sectional area, the length of the storage section, and the number of fibers. Specifically, it is expressed by the following formula. Vc = Cross-sectional area of ​​the housing part × Length of the housing part Vf = fiber cross-sectional area × storage section length × number of fibers Filling rate=Vf / Vc×100(%)…(Formula).

[0070] The cross-sectional area of ​​the housing is the cross-sectional area at the center of the cylindrical case when the cylindrical case has a tapered structure in which the diameter increases toward both ends. Also, when spacer fibers are used to prevent the fibers from sticking together inside the cylindrical case, Vf includes the volume of the spacer fibers.

[0071] In the purification column of the present invention, the capacity of the flow path for the liquid to be treated in the storage section is preferably 5 mL or more and 60 mL or less. Also, in the purification column (II) of the present invention, the capacity of the flow path for the liquid to be treated in the storage section is 5 mL or more and 60 mL or less (requirement (v)). The capacity of the flow path for the liquid to be treated in the storage section refers to the part of the storage section of the purification column minus the fiber volume, and is expressed as follows: Volume of the flow path for the liquid to be treated in the storage section (mL) = Vc - Vf The fiber volume can be calculated by multiplying the total cross-sectional area of ​​the fibers calculated according to the above-mentioned method for measuring the fiber diameter by the length of the fiber bundle placed in the storage section.

[0072] By setting the volume of the flow path for the liquid to be treated in the storage unit to 5 mL or more, more preferably 10 mL or more, even more preferably 15 mL or more, and even more preferably 20 mL or more, it is possible to efficiently remove the adsorbed substances in a given time. On the other hand, by setting the volume to 60 mL or less, more preferably 55 mL or less, even more preferably 50 mL or less, even more preferably 45 mL or less, and even more preferably 40 mL or less, it is possible to obtain a purification column that does not take out a large amount of blood from the body and has a low risk of causing hypotension and anemia.

[0073] In the present invention, the flow path capacity of the entire purification column including the storage section for the liquid to be treated is preferably 10 mL or more and 70 mL or less. By making it 10 mL or more, more preferably 15 mL or more, even more preferably 20 mL or more, and even more preferably 25 mL or more, the distance and space from the inlet port for the liquid to be treated to the storage section can be secured, the liquid to be treated can be prevented from flowing linearly, and the liquid can be diffused and passed uniformly within the header. On the other hand, by making it 70 mL or less, more preferably 60 mL or less, even more preferably 50 mL or less, and even more preferably 40 mL or less, the amount of blood taken out can be reduced.

[0074] In the purification column of the present invention, the equivalent circle diameter of the flow path for the liquid to be treated is preferably 20 μm or more and 100 μm or less. By making it 20 μm or more, more preferably 25 μm or more, even more preferably 30 μm or more, and even more preferably 35 μm or more, the flow path for the liquid to be treated can be secured and an increase in pressure loss during liquid passage can be suppressed. On the other hand, by making it 100 μm or less, more preferably 90 μm or less, even more preferably 80 μm or less, and even more preferably 70 μm or less, it is possible to prevent the flow of the liquid to be treated from being biased toward a specific flow path and not being distributed throughout the entire column, and to efficiently contact the surface of the porous fiber with the liquid to be treated.

[0075] Here, the circle-equivalent diameter of the flow path for the treated liquid can be calculated using the portion of the cross-sectional area occupied by the treated liquid and the wetted perimeter. The wetted perimeter refers to the perimeter of the liquid in contact with the solid wall in the flow path. Equivalent circular diameter of the flow path of the liquid to be treated (μm) = 4 × the amount of liquid to be treated in the cross-sectional area (cm 2 ) / Immersion length (cm)×10000 The amount of liquid to be treated in the cross-sectional area (cm 2 ) = column cross-sectional area - total cross-sectional area of ​​fibers Wetted perimeter (cm) = case inner diameter x π + outer circumference of fiber x number of fibers...(formula).

[0076] Fig. 1 shows a side view illustrating one embodiment of a purification column according to the present invention. In this embodiment, the purification column 1 is provided with a fiber bundle as an adsorbent 5 within a column partitioned by at least a header 2, a distribution plate 3, and a cylindrical case 4. The header 2 is provided with ports that serve as an inlet and an outlet for the liquid to be treated. In Fig. 1, caps are provided to seal the ports.

[0077] The purification column of the present invention has a wide variety of applications, and can be mainly used for separating adsorbed substances from various liquids and gases. In particular, in medical applications, it is preferably used for removing pathogenic proteins, bacteria, viruses, endotoxins, sugar chains, autoantibodies, immune complexes, free light chains, potassium, bilirubin, bile acids, creatinine, phosphorus compounds, drugs, and the like from blood, plasma, and body fluids. Examples of pathogenic proteins include cytokines, β2-microglobulin (β2-MG), low-density lipoproteins, very low-density lipoproteins, and apolipoproteins. In addition, when used in water treatment applications, it is preferably used for removing humic substances, metal corrosion products, and the like.

[0078] In the purification column of the present invention, the pressure loss when bovine blood is passed through the column at a flow rate of 200 mL / min for 1 hour is preferably 1 kPa or more and 20 kPa or less. By setting the pressure to 1 kPa or more, more preferably 1.5 kPa or more, even more preferably 2 kPa or more, and even more preferably 2.5 kPa or more, proteins can easily move inside the porous fibers, improving the adsorption performance. In addition, by setting the pressure to 20 kPa or less, more preferably 10 kPa or less, even more preferably 9 kPa or less, even more preferably 8 kPa or less, and even more preferably 7 kPa or less, it is possible to prevent the shear stress applied to blood cells from increasing and causing hemolysis. The pressure loss can be controlled by adjusting the packing rate of the fibers in the column, the inner diameter of the cylindrical case, the fiber diameter, the number of fibers, etc. A detailed method for measuring the pressure loss will be described later, but it is calculated using the following formula. Pressure loss = inlet pressure of circuit including column - outlet pressure of circuit including column - (inlet pressure of circuit only - outlet pressure of circuit only)... (formula).

[0079] In the purification column of the present invention, the increase in hemolysis rate when bovine blood is passed through the column at a flow rate of 400 mL / min for 4 hours is preferably 1.0 or less. By making the increase in hemolysis rate 1.0 or less, more preferably 0.9 or less, even more preferably 0.8 or less, even more preferably 0.7 or less, and even more preferably 0.6 or less, the risk of hemolysis occurring when blood is removed from a patient can be reduced. The increase in hemolysis rate is expressed by the following formula. Increase in hemolysis rate = hemolysis rate of bovine blood after circulation - hemolysis rate of bovine blood before circulation The detailed method for measuring the hemolysis rate will be described later. The hemolysis rate is calculated by measuring the hemoglobin (Hb) concentration using a measurement kit or the like and using the following formula. Hemolysis rate (%) = hemoglobin concentration in plasma (mg / dL) / total hemoglobin concentration (mg / dL) × 100... (formula).

[0080] The target of adsorption and removal by the purification column of the present invention is β2-MG, which is a causative protein of dialysis amyloidosis, a complication of dialysis. The purification column of the present invention preferably has a β2-MG clearance of 35 mL / min or more and 120 mL / min or less when bovine blood is passed through it at a flow rate of 200 mL / min for 1 hour. By setting the flow rate to 35 mL / min or more, more preferably 40 mL / min or more, even more preferably 50 mL / min or more, and even more preferably 60 mL / min or more, a column having sufficient β2-MG adsorption capacity to obtain excellent therapeutic effects can be prepared. On the other hand, by setting the flow rate to 120 mL / min or less, adhesion of other useful substances in the blood can be suppressed. A detailed method for measuring the adsorption performance of β2-MG will be described later, but it is calculated by measuring the β2-MG concentration before and after passing the liquid through the purification column.

[0081] Fig. 2 shows an example of a circuit diagram for measuring β2-MG clearance in a purification column according to the present invention. In this circuit 6, a pump 7 for circulating the liquid to be treated and a purification column 1 are connected to a tube called a blood circuit. As the liquid to be treated, bovine blood 8 for circulation and bovine blood 9 for clearance are provided, and these are immersed in a hot water bath 10 to keep the temperature constant. A waste beaker 11 is also provided to store the bovine blood for clearance after passing through the purification column.

[0082] The purification column of the present invention preferably has a clearance / storage capacity of 1.0 or more, which is the value obtained by dividing the β2-MG clearance when bovine blood is passed through the purification column at a flow rate of 200 mL / min for 1 hour by the volume of the flow path for the liquid to be treated. Since the clearance / storage capacity represents the adsorption performance per amount of blood taken out, the higher the value, the more the therapeutic effect can be achieved while suppressing the occurrence of anemia during use.

[0083] <Manufacture of fiber bundle and purification column> In the production of the fiber of the present invention, the viscosity of the spinning dope is preferably 10 poise (1 Pa·sec) or more and 100,000 poise (10,000 Pa·sec) or less. By making it 10 poise (1 Pa·sec) or more, more preferably 90 poise (9 Pa·sec) or more, even more preferably 400 poise (40 Pa·sec) or more, and even more preferably 800 poise (80 Pa·sec) or more, the fluidity of the dope becomes appropriate and it becomes easy to maintain the desired shape. On the other hand, by making it 100,000 poise (10,000 Pa·sec) or less, more preferably 50,000 poise (5,000 Pa·sec) or less, the pressure loss during the dope discharge does not increase, the discharge stability is maintained, and the dope becomes easy to mix.

[0084] The viscosity is measured by the falling ball method in a thermostatic chamber set at the spinning temperature in accordance with JIS Z 8803:2011. Specifically, a viscosity tube with an inner diameter of 40 mm is filled with the spinning solution, a steel ball with a diameter of 2 mm (made of SUS316) is dropped into the solution, and the time required for the ball to fall 50 mm is measured. The temperature during measurement is 92°C.

[0085] A spinning dope is prepared by dissolving a polymer in a solvent within the above range. At this time, the lower the dope polymer concentration (the concentration of the substances in the dope excluding the solvent) is, the larger the pore size of the fiber can be, so by appropriately setting the dope polymer concentration, it is possible to control the pore size and pore volume. From this viewpoint, the dope polymer concentration in the present invention is preferably 30% by mass or less, more preferably 27% by mass or less, and even more preferably 24% by mass or less.

[0086] In addition, the pore size and pore volume can be controlled by using a polymer having a negatively charged group. When using a polymer having, for example, methacrylic acid or p-styrenesulfonic acid as a negatively charged group, the proportion of the polymer having methacrylic acid or p-styrenesulfonic acid in the total polymer is preferably 10 mol % or less.

[0087] In order to produce a fiber having a non-circular cross section as the fiber of the present invention, it is advisable to control the shape of the outlet of the spinneret in addition to the spinning dope composition and the dry section. For example, it is preferable to configure the spinneret with a center circle, a slit, and a circle at the tip of the slit, and to appropriately design the center circle diameter, slit section width, slit section length, and tip circle diameter. When the spinneret is of such a preferred shape, the cross-sectional area of ​​the outlet of the spinneret is appropriate, so that the draft in the dry section does not become too large, and unevenness in the fiber diameter and irregularity, which is called draw resonance, is unlikely to occur, and spinning is easy.

[0088] The spinning method for obtaining the fiber in the present invention may be either melt spinning or solution spinning. In solution spinning, a spinneret is used to pass the stock solution through a dry air section for a certain distance, and then the solution is discharged into a coagulation bath consisting of a poor solvent such as water or a non-solvent to obtain the fiber.

[0089] The production of porous fibers having a porous structure is not limited to the manufacturing method of thermally induced phase separation or non-solvent induced phase separation, but non-solvent induced phase separation is preferable because the solvent is rapidly removed during immersion in a coagulation bath, making it relatively easy to obtain a porous shape. In addition, the conditions of the dry and wet parts may be any of dry, wet, and dry and wet, but the dry and wet type is particularly preferable because the porous structure of the fiber surface can be precisely controlled depending on the dry and wet part conditions. In addition, although the detailed mechanism is unclear, it is possible to control the unevenness and surface roughness of the porous fiber surface by adjusting the cold air temperature and dew point. For example, by increasing the cold air speed to increase the cooling efficiency, the surface opening rate of the fiber and the pore size near the outer periphery of the fiber can be increased.

[0090] The draft ratio during discharge is preferably 1.5 or more and 30 or less. The draft ratio is a parameter defined as the ratio of the fiber take-up speed to the speed at which the spinning dope leaves the spinneret. By setting the draft ratio to 1.5 or more, more preferably 3 or more and 30 or less, the fiber can be stretched under an appropriate tension, and it is possible to prevent the fiber from being blown by cold air or outside air to some extent. In addition, under spinning conditions in which a dry section exists, the pores of the fiber are stretched to become elliptical, so that the surface area per space is smaller than that of spherical pores. This makes it possible to obtain a fiber that has both a high separation amount and sharp separation ability.

[0091] In solution spinning, the spinning solution discharged from the spinneret is coagulated in a coagulation bath. The coagulation bath generally consists of a coagulant such as water or alcohol, or a mixture with the solvent that constitutes the spinning solution. Water is generally chosen from the viewpoints of ease of wastewater treatment, safety for living organisms during production, and risk of ignition and leakage. In addition, the pore size can be changed by controlling the temperature of the coagulation bath. Since the pore size is affected by the temperature during phase separation and the environment around the polymer, the temperature of the coagulation bath is also appropriately selected. In general, the pore size can be increased by increasing the coagulation bath temperature. Although the exact mechanism is not clear, it is thought that this is because the desolvation from the solution and the coagulation shrinkage compete with each other, and the desolvation is faster in a high-temperature bath, and the fiber is coagulated and fixed before the inside of the fiber shrinks. For example, when the fiber contains PMMA, the coagulation bath temperature is preferably 90°C or less, more preferably 75°C or less, and particularly preferably 65°C or less. When the upper limit of the coagulation bath temperature is within the above-mentioned preferred range, the pore size does not become too large, so that the pore specific surface area does not decrease, the strength and elongation do not decrease, and non-specific adsorption does not increase. The lower limit of the coagulation bath temperature is preferably 5°C or higher, and more preferably 20°C or higher. When the lower limit of the coagulation bath temperature is within the above-mentioned preferred range, the pore size does not become too small, and the adsorbed substance is easily diffused inside the pores.

[0092] Next, the fibers are washed to remove the solvent adhering to the coagulated fibers. The means for washing the fibers is not particularly limited, but a method of passing the fibers through a multi-stage water bath (called a water washing bath) is preferably used. The temperature of the water in the water washing bath may be insufficient in washing effect if the washing temperature is too low, and may not be usable as a washing liquid if the washing temperature is too high. In addition, it is preferable to determine the temperature according to the properties of the polymer constituting the fibers. Taking into consideration washing efficiency, for example, in the case of a fiber containing PMMA, the temperature is preferably 30°C or higher and 50°C or lower. Here, the time for immersion in the water washing bath is also appropriately selected depending on the fiber diameter and spinning speed. If the washing process is insufficient and there is a large amount of remaining solvent, the fiber structure may be altered and handling after winding may become difficult, so it is preferable to wash thoroughly. In addition, if it is necessary to impart a certain amount of pore-forming agent or modifier to the fiber, excessive washing is not preferable.

[0093] In addition, in order to maintain the pore size after the water washing bath, a process of adding a moisturizing component to the fiber may be performed. The moisturizing component here refers to a component capable of maintaining the moisture of the fiber or a component capable of preventing the moisture of the fiber from decreasing in the air. Representative examples of moisturizing components include glycerin and its aqueous solution.

[0094] After washing with water and adding a moisturizing component, the fiber may be passed through a bath filled with a heated aqueous solution of the moisturizing component (called a heat treatment bath) in order to improve the dimensional stability of the highly shrinkable fiber. The heat treatment bath is filled with a heated aqueous solution of the moisturizing component, and the fiber is subjected to thermal action and shrinks when it passes through this heat treatment bath, making it difficult to shrink in subsequent processes, and stabilizing the fiber structure. If the fiber structure is not stabilized, the fiber will shrink anisotropically between the time of manufacture and actual use, resulting in a different arrangement from that at the time of manufacture, causing flow unevenness and a decrease in adsorption performance, which is not preferable. The heat treatment temperature at this time varies depending on the fiber material, but is preferably set to 50°C or higher, more preferably 80°C or higher, even more preferably 95°C or higher, and even more preferably 97°C or higher in the case of fibers containing PMMA.

[0095] It is preferable that the fiber is then introduced into the winding section via a tension control mechanism such as a dancer roll so that the fiber can be smoothly wound while maintaining a constant tension. The tension control mechanism is not limited to a dancer roll, and may be any mechanism that varies or relieves the tension applied to the fiber, such as two or more drive rolls or a roll with projections and recesses in the circumferential direction.

[0096] In the method for producing a fiber bundle of the present invention, it is important that the tension during winding is 0.5 g / fiber or more and 10.0 g / fiber or less (requirement (a)). By setting the tension to 0.5 g / fiber or more, more preferably 0.9 g / fiber or more, even more preferably 1.0 g / fiber or more, even more preferably 1.3 g / fiber or more, even more preferably 1.5 g / fiber or more, and even more preferably 1.7 g / fiber or more, it is possible to prevent the fibers from swelling and meandering during winding. In addition, by setting the tension to 10.0 g / fiber or less, more preferably 8.0 g / fiber or less, even more preferably 5.0 g / fiber or less, and even more preferably 3.0 g / fiber or less, it is possible to prevent brittle fracture of the fibers contained in the fiber bundle. When the fibers are plastically deformed, they do not return to their original length even after being released from the tension, so for fibers with a small elastic deformation region, it is preferable to keep the tension applied within the above range. In addition, by winding the fibers together in an appropriate number, it is possible to align the fibers (multiple fibers are called a tow) and prevent deformation. In this way, the tension is distributed among a plurality of fibers, and the force is not concentrated on a single fiber, so that the above-mentioned preferable effect can be stably obtained. In the purification column of the present invention, the linearity of the fibers in the fiber bundle cannot be improved in the process after winding, so the application of tension before winding is extremely important.

[0097] A reel is used for winding because it can prevent the fibers from meandering. The reel used can have various shapes, but a polygonal shape is preferable.

[0098] Before the fibers are wound onto the skein, they are reciprocated at a predetermined speed in a direction perpendicular to the skein axis via a traverse mechanism, and the fiber bundle is wound evenly without unevenness. In this case, as long as the method is capable of winding the fiber bundle evenly without unevenness, the fibers may be moved relative to the skein by a guide or roller in the traverse mechanism, or the skein itself may be moved in parallel.

[0099] In the fiber bundle manufacturing method of the present invention, it is important that the traverse movement distance (the distance traveled parallel to the direction perpendicular to the traveling direction of the fibers) is 0.1 mm or more and 30 mm or less during one rotation of the skein (requirement (b)). By making the distance 0.1 mm or more, more preferably 0.5 mm or more, even more preferably 1.0 mm or more, and even more preferably 1.3 mm or more, it is possible to prevent the arrangement of the fibers in the fiber bundle from becoming unevenly dense, and to obtain a fiber bundle having a shape close to a perfect circle. In addition, by making the distance 30 mm or less, more preferably 25.0 mm or less, even more preferably 20.0 mm or less, even more preferably 15.0 mm or less, and even more preferably 10.0 mm or less, it is possible to reduce the force applied to the fibers when the traverse movement direction is changed, and to reduce the breakage, damage, and derailment of the fibers from the traverse roller, and further to prevent the fibers from meandering in the fiber bundle and complicating the flow path of the liquid to be treated.

[0100] In addition, when multiple fibers are wound together, it is preferable to set the traverse movement distance so that the tows are not piled up after one rotation and are in contact with each other side by side without any gaps. The traverse movement distance when the skein rotates once may be a constant value within the above range or may be changed during winding.

[0101] In addition, it is preferable to change the traverse stroke during winding so that it matches the final fiber bundle shape. The traverse stroke is the maximum distance that the traverse roller moves in a direction perpendicular to the skein axis, and the fibers repeat reciprocating motion within the stroke via the traverse mechanism. When concentrating the fiber bundle to be used in the purification column of the present invention, it is preferable that the average value of the traverse stroke satisfies the relationship of middle stage>end stage=initial stage in the initial, middle stage, and final stages of winding involving traverse (requirement (c)). Here, "=" means equal at the level of 1 mm, and the relationship of large and small means that there is a difference of 1 mm or more. By making the relationship as described above, it is possible to obtain a fiber bundle having a shape whose cross section is close to a perfect circle by making it small in the initial stage, large in the middle stage that forms the center of the fiber bundle, and small again in the final stage and equal to the initial stage.

[0102] In addition, although the program may be set up to change the traverse continuously during winding, it has been found that it is preferable to change the traverse stroke discontinuously after careful consideration. Specifically, it is preferable to change the traverse stroke by any one of 4, 6, 8, 10, and 12 (requirement (d)). As described above, in order to maximize the traverse stroke in the middle stage of winding the fiber, it is necessary to change the traverse stroke an even number of times. Here, the initial stage of the traverse is the period until the (number of traverse stroke changes / 2-1)th change is made, the middle stage is the period from the (number of traverse stroke changes / 2-1)th change to the (number of traverse stroke changes / 2+1)th change, and the final stage is the period after the (number of traverse stroke changes / 2+1)th change is completed. By changing the traverse stroke stepwise, it is possible to suppress the tow from slipping at the point where the traverse movement direction is switched (which constitutes the outer periphery when the fiber bundle is formed), and the fiber from meandering in the obtained fiber bundle.

[0103] The number of changes in the traverse stroke is preferably 4 to 12 times. By changing the number of times to 4 or more, the cross section of the obtained fiber bundle can be made to have a shape close to a perfect circle. Also, by changing the number of times to 12 or less, in addition to the above-mentioned effect of suppressing slippage and meandering, it can be implemented with a simple program, and it can be manufactured relatively easily.

[0104] After this, the fiber bundle is cut out from the reel and inserted into a cylindrical case. As a method for fixing the fiber bundle end in the cylindrical case, there is a method of arranging a mesh, or a method of fixing with resin to communicate the partition wall and providing a hole penetrating the inside and outside of the cylindrical case. Here, the through hole refers to an opening that communicates in the longitudinal direction of the fiber in the partition wall. To form the through hole, a method of inserting a small pin-shaped tube into the end surface of the fiber bundle and then pouring resin near the end surface to perform potting can be mentioned. After the resin has solidified, both ends are cut with a cutter or the like to remove the part of the fiber blocked by the resin, and the pin-shaped tube is removed, and the opening of the through hole is formed at the end of the pot layer. However, compared to the case where a distribution plate is used as described later, in addition to the process being complicated, there is a risk that the liquid to be treated will generally stagnate or turbulent, making it difficult to control the flow into the purification column. On the other hand, the method of arranging a mesh is more preferable because the process is easier than the method of forming partition walls, and the liquid is highly dispersible in the purification column.

[0105] In order to further increase the dispersibility of the liquid to be treated in the purification column, a plate for controlling the flow, such as a distribution plate, may be added. The distribution plate has a structure in which a convex portion is inserted into the fiber bundle, or a structure in which an opening portion is partitioned in the flow direction. In the purification column according to the present invention, it is preferable that a distribution plate is arranged on at least one end face side, and has a plurality of opening portions through which the liquid to be treated can communicate, a support, and a convex portion extending from the support to the fiber side, and at least a part of the convex portion is inserted into the fiber bundle. By appropriately adjusting the insertion angle, depth, opening area, and partition shape of the convex portion, the flow resistance in the flow direction can be controlled so as to incline from a place where it is originally easy to flow to a place where it is difficult to flow. As a result, the flow of the liquid to be treated can be made uniform, and retention can be suppressed.

[0106] As described above, a purification column can be obtained by attaching a header and a mesh to both ends of the cylindrical case. EXAMPLES

[0107] An embodiment of the present invention is illustrated in the following examples.

[0108] [Measurement method] (1) Surface open area of ​​the fiber The fibers to be evaluated were fixed on the substrate with double-sided tape. Morphological observation was performed in a wet state using an atomic force microscope SPI3800 (Seiko Instruments). The observation mode was DMF mode, and the observation field was 3 μm × 3 μm, with a total of 10 fields of view measured. The pixel setting for observation was 512 × 512 pixels or more. The obtained AFM images were analyzed using software attached to the Seiko Instruments AFM. The images were binarized using "Automatic threshold selection method based on discrimination and least squares criteria" (Nobuyuki Otsu, Journal of the Institute of Electronics and Communication Engineers, 63, pp. 349-356 (1980)) to extract information on the unevenness of the film surface. After binarization, the area ratio of the black parts of the binarized components was calculated as the surface opening rate by image analysis.

[0109] (2) Dry Ra value After thoroughly wetting the fiber, it was immersed in liquid nitrogen, and the water in the pores was instantly frozen with liquid nitrogen. The frozen water was then removed in a vacuum dryer at 0.1 torr (13.3 Pa) or less to obtain a dry sample. The dry sample was cut to about 5 mm and fixed to a silicon wafer with double-sided tape. The morphology was observed in a dry state using a scanning probe microscope (Bruker NanoScope V Dimension Icon). The surface opening was excluded from the contact surface measurement. The observation mode was peak force tapping, the cantilever was a SiN cantilever, and the observation field was 3 μm x 3 μm. The probe was scanned near the apex of the fixed porous fiber so that it was almost perpendicular to the longitudinal direction of the fiber. Three fibers were randomly selected for each measurement target, and one location was observed for each fiber. The dry Ra value of the fiber was calculated by the arithmetic average of each measurement value.

[0110] (3) Wet Ra value The fibers were cut to about 5 mm and fixed to a silicon wafer with double-sided tape. The morphology was observed in a wet state using a scanning probe microscope (Bruker NanoScope V Dimension FastScan Bio). Three fibers were randomly selected for each measurement target, and one spot was observed for each fiber. The wet Ra value of the fiber was calculated by the arithmetic average of each measurement value.

[0111] (4) Degree of irregularity Both ends of the fiber to be measured are 0.1 g / mm 2 The fiber was fixed with tension of 0.01 mm and cut at random positions. The cut surface was magnified and photographed with an optical microscope (DIGITAL MICROSCOPE DG-2, Scalar Corporation). When taking the photograph, a scale was also photographed at the same magnification. After the image was digitized, the diameter Do of the circumscribed circle and the diameter Di of the inscribed circle of the cross section of the fiber were measured using image analysis software ("Micro Measure" ver.1.04, Scalar Corporation). The irregularity of each fiber was then calculated using the following formula. Anomalousness = Do / Di This measurement was carried out at 30 locations, the values ​​were averaged, and the average value was rounded off to two decimal places to obtain the irregularity degree.

[0112] (5) Equivalent circle diameter Both ends of the fiber to be measured are measured with a pressure of 0.01 to 0.10 g / mm 2 The fiber was fixed and cut under tension. The cut surface was magnified and photographed with an optical microscope. A scale was also photographed at the same magnification. The image was digitized, and then the outer periphery of the cross section of the fiber was plotted using image analysis software (Scala Corporation "Micro Measure" ver.1.04), and the points were connected in the software to calculate the cross-sectional area S, and the circle equivalent diameter of each opening was calculated using the following formula. Equivalent circular diameter of fiber cross section = 2 × (S / 2π) The average of the 30 measured values ​​was calculated and rounded to the first decimal place.

[0113] (6) Length of a single fiber One end of a fiber is fixed with tape or the like and hung vertically, and the other end is attached to a 2 ) was attached with a 10 g weight, and the total length when the fiber became straight was immediately measured. This measurement was performed on 100 randomly selected fibers, and the average value was calculated. For example, if the length of one fiber actually used in measurement 1 is obtained as a value 1 mm or more shorter than the "fiber bundle length" which is the average value of 10 arbitrary points, this fiber is considered to have been cut in the fiber bundle, or the fiber end was damaged and shortened after the manufacturing process, so the data is not included in the population of 100 fibers, and another fiber sample is selected and used for measurement.

[0114] (7) Adsorption performance of TNFα and IgG Commercially available human recombinant TNFα (manufactured by R&D) was added to commercially available human serum (manufactured by Cosmo Bio) to a concentration of 1 μg / mL to prepare TNFα-added human serum. 6 mL of the TNFα-added human serum was placed in a 15 mL centrifuge tube (manufactured by Greiner), and the fibers were placed in the tube at a distance of 0.0142 cm. 3 The mixture was then shaken side to side at a shaking speed of 30±1 strokes per minute for 4 hours at 37°C. Serum was collected before and after shaking, and the TNFα and IgG concentrations were quantified using ELISA and immunoturbidimetry, respectively. The adsorption performance of each was calculated using the following formula. Adsorption performance of TNFα (μg / cm 3 )=(C1-C2)×6 / 0.0142 IgG adsorption capacity (mg / cm 3 )=(C3-C4)×6 / 0.0142 Here, C1: TNFα concentration before shaking (μg / mL) C2: TNFα concentration after shaking (μg / mL) C3: IgG concentration before shaking (mg / mL) C4: IgG concentration after shaking (mg / mL).

[0115] (8) β2-MG clearance in purification columns The bovine blood containing disodium ethylenediaminetetraacetate was adjusted to a hematocrit of 30±3% and a total protein content of 6.5±0.5g / dL. The bovine blood was used within 5 days of collection. 1.2L of the bovine blood was divided into two parts: one for circulation and the other for clearance measurement. The β2-MG concentration was then adjusted to 1mg / L and mixed with the bovine blood for clearance measurement. The blood circuit and pump were set so that bovine blood could circulate, and a purification column was connected. The blood circuit inlet was placed in a circulation beaker containing 1.2 L (37 ° C) of bovine blood prepared as described above, the flow rate was set to 200 mL / min, the pump was started, the bovine blood discharged from the blood circuit outlet was discarded for 90 seconds, and the blood circuit outlet was immediately inserted into the circulation beaker to circulate. After circulation for 1 hour, the pump was stopped. Next, the blood circuit inlet was placed in the bovine blood for clearance measurement prepared as described above, and the blood circuit outlet was placed in a disposal beaker. The flow rate was set to 200 mL / min, and 4 minutes after the start of the pump, 10 mL was collected from the bovine blood for clearance measurement (37 ° C) and used as Bi liquid. 4 minutes and 50 seconds after the start, 10 mL of the sample flowing from the blood circuit outlet was collected and used as Bo liquid. Then, Bi liquid and Bo liquid were centrifuged, and the supernatant bovine plasma was collected. These samples were stored in a freezer at -20°C or below. The clearance was calculated from the β2-MG concentration in each solution using the following formula. CL(mL / min)=QB×(CBi-CBo) / CBi×(100-Ht) / 100…(I) Here, CL: β2-MG clearance (mL / min) QB: Pump flow rate (mL / min) CBi: β2-MG concentration in Bi solution (μg / L) CBo: β2-MG concentration in Bo solution (μg / L) Ht: hematocrit value (%) of bovine blood used for clearance measurement.

[0116] (9) Pressure loss In the above (8) β2-MG clearance measurement, the pressure difference between the inlet (Bi) and outlet (Bo) was measured 4 minutes after passing bovine blood for clearance measurement. Furthermore, the pressure difference between Bi and Bo was measured under the same conditions for the circuit only, without connecting the purification column. The pressure loss was calculated using the following formula. Pressure loss = Bi when column is connected - Bo when column is connected - (Bi when only circuit is connected - Bo when only circuit is connected) ... (formula).

[0117] (10) Hemolysis rate Bovine blood prepared in the same manner as in (8) above and a blood circuit set up in the same manner were used. At the start of circulation, 5 mL of bovine blood was collected. Then, 1 L of bovine blood was circulated at a flow rate of 400 mL / min for 4 hours. After 4 hours of circulation, 3 mL of circulating fluid was collected. 3 mL of the bovine blood at the start of circulation and the bovine blood after 4 hours of circulation were centrifuged, and the supernatant was collected. The hemoglobin concentration of the obtained plasma was quantified using a measurement kit (Hemoglobin B-Test Wako, Fujifilm Wako Pure Chemical Industries, Ltd.). The total hemoglobin concentration of the bovine blood collected at the start was also measured using the same measurement kit, and the hemolysis rate was calculated from the following formula. Hemolysis rate (%) = hemoglobin concentration in plasma (mg / dL) / total hemoglobin concentration (mg / dL) × 100 Furthermore, the increase in hemolysis rate was calculated using the following formula. Increase in hemolysis rate = hemolysis rate of bovine blood after circulation - hemolysis rate of bovine blood before circulation... (formula).

[0118] [Example 1] (Preparation of PMMA fiber bundles) 31.7 parts by mass of syndiotactic PMMA (hereinafter, syn-PMMA) with a mass average molecular weight of 400,000, 31.7 parts by mass of syn-PMMA with a mass average molecular weight of 1.4 million, 16.7 parts by mass of isotactic PMMA (hereinafter, iso-PMMA) with a mass average molecular weight of 500,000, 20 parts by mass of PMMA copolymer with a molecular weight of 300,000 containing 1.5 mol% sodium parastyrene sulfonate were mixed with 376 parts by mass of dimethyl sulfoxide and stirred at 110 ° C for 8 hours to prepare a spinning dope. The viscosity of the obtained spinning dope at 92 ° C was 1,880 poise (188 Pa s). The obtained spinning dope was discharged from two types of spinnerets with different irregularly shaped discharge holes at a speed of 1.1 g / min, and after running 380 mm in the dry section, it was introduced into a coagulation bath and passed through the bath. The temperature of the atmosphere in the dry section was 15°C, and cold air with a dew point of 12°C was applied perpendicularly to the fibers. Water was used in the coagulation bath, and the water temperature (coagulation bath temperature) was 42.5°C. After washing each fiber with water, it was introduced into a bath of an aqueous solution containing 70% by mass of glycerin as a moisturizing agent, and then passed through a heat treatment bath at a temperature of 84°C to relieve residual stress, after which excess glycerin was removed with a scraper and the fiber was wound up at 45 m / min on a skein. The tension during winding and the traverse movement distance per revolution were performed under the conditions shown in Table 1. The number of traverse stroke changes was set to 6 times. In this way, a fiber bundle containing 136,000 fibers and including porous fibers having two types of irregular cross-sectional shapes was obtained.

[0119] The average pore radius of the porous fibers was within the range of 2.5 to 22 nm, the average pore diameter in the region near the outer surface / the average pore diameter in the central region was within the range of 0.85 to 1.50, and the aperture ratio of the openings on the fiber surface was within the range of 2 to 15%.

[0120] (Preparation of purification column) A purification column was made using the obtained fiber bundle. The fiber bundle was inserted into a cylindrical case with a length of 42 mm and an inner diameter of 52 mm, and the excess was cut off except for a part of the fiber bundle that protruded from the cylindrical case, and the fiber bundle was stored in the cylindrical case approximately parallel to the longitudinal direction. A distribution plate and a mesh header were attached to both ends of the cylindrical case to form a column. The distribution plate used had a double annular convex portion and was shaped so that it was equally distributed into nine sections in a circumferential shape. The area ratio of the flow path cross section excluding the support pillars of the distribution plate was approximately 60%. After columnization, the glycerin remaining in the porous fiber was washed with water, and the column was filled with water, and then sterilized by irradiating with 25 kGy of gamma rays.

[0121] [Example 2] A purification column was prepared in the same manner as in Example 1, except that the discharge rate of the spinning dope was changed to 1.2 g / min to set the equivalent circle diameter of the fiber to 117 μm. The average pore radius of the porous fiber was within a range of 2.5 to 22 nm, the average pore diameter in the region near the outer surface / the average pore diameter in the central region was within a range of 0.85 to 1.50, and the aperture ratio of the openings on the fiber surface was within a range of 2 to 15%. The results of the various measurements are shown in Table 1.

[0122] [Example 3] A purification column was produced in the same manner as in Example 1, except that the discharge rate of the spinning dope was changed to 1.0 g / min, the equivalent circle diameter of the fiber was 110 μm, the number of fibers in the fiber bundle was 83,000, the length of the storage section of the cylindrical case was 55 mm, and the inner diameter of the storage section was 41 mm. The average pore radius of the porous fiber was within a range of 2.5 to 22 nm, the average pore diameter in the region near the outer surface / the average pore diameter in the central region was within a range of 0.85 to 1.50, and the aperture ratio of the openings on the fiber surface was within a range of 2 to 15%. Table 1 shows the results of various measurements.

[0123] [Example 4] A purification column was produced in the same manner as in Example 1, except that the tension during winding was changed to 1.8 gf / piece, and the traverse movement distance per rotation of the skein was changed to 1.3 mm. The average pore radius of the porous fiber was within a range of 2.5 to 22 nm, the average pore diameter in the region near the outer surface / the average pore diameter in the central region was within a range of 0.85 to 1.50, and the aperture ratio of the openings on the fiber surface was within a range of 2 to 15%. The results of various measurements are shown in Table 1.

[0124] [Comparative Example 1] Except for changing the number of fibers in the fiber bundle to 80,000, a purification column was produced in the same manner as in Example 1. Various measurement results are shown in Table 1.

[0125] [Comparative Example 2] Except for changing the number of fibers in the fiber bundle to 165,000, a purification column was produced in the same manner as in Example 1. Various measurement results are shown in Table 1.

[0126] [Comparative Example 3] A purification column was prepared in the same manner as in Example 1, except that the number of fibers in the fiber bundle was changed to 45,000, the length of the storage section of the cylindrical case was changed to 80 mm, and the inner diameter of the storage section was changed to 30 mm. Various measurement results are shown in Table 1.

[0127] [Comparative Example 4] A purification column was produced in the same manner as in Example 1, except that the number of fibers in the fiber bundle was changed to 240,000, the length of the storage section of the cylindrical case was changed to 25 mm, and the inner diameter of the storage section was changed to 70 mm. Various measurement results are shown in Table 1.

[0128] [Comparative Example 5] A purification column was prepared in the same manner as in Example 1, except that a fiber bundle that was wound around a skein without applying tension was used. Various measurement results are shown in Table 1.

[0129] [Comparative Example 6] A purification column was prepared in the same manner as in Example 1, except that a fiber bundle that was wound around a skein without using a traverse mechanism was used. Various measurement results are shown in Table 1.

[0130] [Comparative Example 7] In the preparation of the fiber bundle, 16 parts by mass of polysulfone (Udel Polysulfone (registered trademark) P-3500 manufactured by Solvay) was mixed with 84 parts by mass of N,N-dimethylacetamide (DMAc) and stirred at 60°C for 8 hours to prepare a spinning dope. The obtained spinning dope was discharged from a cylindrical nozzle, run through a dry section for 350 mm, and then introduced into a coagulation bath and passed through the bath. As the atmosphere in the dry section, cold air with a temperature of 30°C and a humidity of 80% was applied perpendicularly to the porous fiber. Water was used in the coagulation bath, and the water temperature (coagulation bath temperature) was 40.0°C. After washing with water, each porous fiber was wound up at 30 m / min by a skein. Various measurement results are shown in Table 1.

[0131] [Comparative Example 8] A purification column was prepared in the same manner as in Example 1, except that the temperature of the atmosphere in the dry section in the spinning was set to 1° C. and the dew point of the cold air was set to −20° C. Various measurement results are shown in Table 1.

[0132] [Comparative Example 9] A purification column was prepared in the same manner as in Example 1, except that the temperature of the atmosphere in the dry section in the spinning was 25° C. and the dew point of the cold air was 20° C. The results of various measurements are shown in Table 1.

[0133] [Table 1]

[0134] Comparing Example and Comparative Example 1, it can be seen that the adsorption performance of β2-microglobulin significantly decreases with a decrease in the packing rate. This is because the amount of fiber is small, and the treated liquid flows between the fibers, making it difficult for the treated liquid to come into sufficient contact with the fibers. Comparing Example 1 and Comparative Example 2, it can be seen that the pressure loss increases with an increase in the packing rate, and the hemolysis rate increases further. It is presumed that when the pressure loss is large, the shear stress applied to the blood cells increases, causing hemolysis.

[0135] A comparison of Example 1 with Comparative Examples 3 and 4 shows that, with the fiber packing rate at the same level, when the inner diameter of the storage section is small, the pressure loss increases, and when it is large, the adsorption performance decreases. This is presumably because when the inner diameter of the storage section is small, the flow rate per cross-sectional area increases, and when the inner diameter of the storage section is large, the liquid to be treated does not flow to the outer periphery, resulting in the generation of fibers that do not contribute to the adsorption performance.

[0136] In comparison between Example 1 and Comparative Examples 5 and 6, when the manufacturing method such as the winding conditions was changed, the fiber bundle meandered and the linearity decreased. When the linearity was less than 0.97, the pressure loss increased, and the hemolysis rate further increased. When the pressure loss was large, the shear stress applied to the blood cells increased. Furthermore, it is presumed that the hemolysis was caused as a result of the increased opportunities for contact, collision, and abrasion between the blood cells and the fibers.

[0137] Comparing Example 1 with Comparative Example 7, it is found that when the value expressed by wet Ra / dry Ra is outside the patent range, that is, less than 1.05, the amount of IgG adsorbed increases. This is presumably due to the polymer chains on the fiber surface not being sufficiently swollen.

[0138] In comparison between Example 1 and Comparative Example 8, when the dry Ra value and the wet Ra value are small, the adsorption performance of TNFα is significantly decreased. Furthermore, the adsorption performance of β2-microglobulin is also decreased in the purification column manufactured using this fiber bundle. This is presumably because, when the fiber surface is smooth, the flow of the treated liquid near the surface becomes straight, and a boundary layer is generated.

[0139] In comparison between Example 1 and Comparative Example 9, when the dry Ra value and the wet Ra value are large, the amount of IgG adsorbed increases. Furthermore, it is found that the purification column manufactured using this fiber bundle has an increased hemolysis rate. This is presumably because blood cells have more opportunities to come into contact with, collide with, and be rubbed against the unevenness of the fiber surface, causing hemolysis. [Explanation of symbols]

[0140] 1 Purification column 2. Header 3 Distribution plate 4 Cylindrical case 5 Adsorbent 6 β2-MG clearance measurement circuit 7. Pump 8. Circulating Bovine Blood 9. Bovine Blood for Clearance 10 Hot water bath 11 Waste beaker

Claims

1. A fiber bundle comprising a plurality of porous fibers, which satisfies the following requirements (A) to (E). (A) The porous fiber has a solid shape. (B) The arithmetic mean roughness (dry Ra value) of the surface of the porous fiber in a dry state is 11 nm or more and 30 nm or less. (C) The arithmetic mean roughness (wet Ra value) of the surface of the porous fiber in a wet state is 12 nm or more and 40 nm or less. (D) The value represented by wet Ra / dry Ra is 1.05 or more. (E) The linearity of the fiber bundle, expressed as (length of fiber bundle) / (length of one porous fiber), is 0.97 to 1.

00.

2. 2. The fiber bundle according to claim 1, wherein the degree of irregularity of the cross section of the porous fiber, expressed as Do / Di, is 1.3 or more and 8.5 or less, where Di is the diameter of the inscribed circle and Do is the diameter of the circumscribed circle in the cross section of the porous fiber.

3. The fiber bundle according to claim 1 or 2, wherein the average pore radius of the porous fibers is 0.8 nm or more and 90 nm or less.

4. The fiber bundle according to any one of claims 1 to 3, wherein the porous fibers have a uniform porous structure in the cross-sectional direction.

5. The fiber bundle according to any one of claims 1 to 4, wherein the surface opening ratio of the porous fibers is 0.1% or more and 30% or less.

6. The fiber bundle according to any one of claims 1 to 5, wherein the cross-sectional circle equivalent diameter of the porous fiber is 10 µm or more and 1000 µm or less.

7. The amount of IgG adsorbed by the porous fiber was 13 mg / cm ３ The fiber bundle according to any one of claims 1 to 6, wherein:

8. The adsorption capacity of the porous fiber for tumor necrosis factor alpha (TNFα) was 15 μg / cm ３ The fiber bundle according to any one of claims 1 to 7.

9. A purification column comprising: a fiber bundle according to any one of claims 1 to 8 housed in a cylindrical case so as to be approximately parallel to the longitudinal direction of the cylindrical case; and headers each having an inlet port and an outlet port for a liquid to be treated attached to both ends of the cylindrical case.

10. A purification column comprising a fiber bundle formed by bundling two or more fibers and housed in a cylindrical case so as to be approximately parallel to the longitudinal direction, and headers each having an inlet port and an outlet port for a liquid to be treated attached to both ends of the cylindrical case, and which satisfies the following requirements (i) to (v): (i) In the cross section of the fiber, the diameter of the inscribed circle is Di and the diameter of the circumscribed circle is Do, and the irregularity of the cross section of the fiber, expressed as Do / Di, is 1.3 or more and 8.5 or less. (ii) The filling rate of the fiber in the storage portion is 40% or more and 73% or less. (iii) The inner diameter of the housing is 32 mm or more and 60 mm or less. (iv) The linearity of the fiber, expressed as (the length of the fiber bundle contained in the purification column) / (the length of one fiber contained in the purification column), is 0.97 or more and 1.00 or less. (v) The capacity of the flow path for the liquid to be treated in the storage section is 5 mL or more and 60 mL or less.

11. 11. The purification column according to claim 10, wherein the pressure loss when bovine blood is passed through the column at a flow rate of 200 mL / min for 1 hour is 1 kPa or more and 20 kPa or less.

12. 12. The purification column according to claim 10 or 11, wherein the increase in hemolysis rate, expressed by the following formula, when bovine blood is passed through the column at a flow rate of 400 mL / min for 4 hours is 1.0 or less. Increase in hemolysis rate = hemolysis rate of bovine blood after circulation - hemolysis rate of bovine blood before circulation

13. The purification column according to any one of claims 10 to 12, wherein the β2-microglobulin (β2-MG) clearance when bovine blood is passed through the column at a flow rate of 200 mL / min for 1 hour is 35 mL / min or more and 120 mL / min or less.

14. A method for producing a fiber bundle as described in any one of claims 1 to 8, comprising bundling the fibers under conditions that satisfy the following (a) and (b): (a) The tension when the fiber is wound onto a skein is 0.5 gf / skein or more and 10.0 gf / skein or less. (b) the traverse movement distance (the distance traveled parallel to the direction perpendicular to the traveling direction of the fiber) during one rotation of the skein is 0.1 mm or more and 30 mm or less;

15. The method for producing a fiber bundle according to claim 14 , further comprising bundling the fibers under conditions that satisfy the following (c) and (d): (c) The average value of the traverse stroke (the maximum distance that the traverse roller moves in the axial direction of the skein) during winding of the fiber onto the skein satisfies the relationship of middle stage>final stage=initial stage in the initial, middle, and final stages of winding involving traverse. (d) the number of changes in the traverse stroke is any one of 4, 6, 8, 10, and 12;

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