Title of the invention: Fiber bundle and its manufacturing method and purification column
Technical field
[0001]
　The present invention relates to a fiber bundle used for removing a substance to be adsorbed in a liquid to be treated by adsorption, a method for producing the same, and a purification column.
Background technology
[0002]
　Purification columns used for removing substances to be adsorbed in a liquid to be treated by adsorption are used in a wide range of fields. In particular, in the medical field, it is used for blood purification therapy in which a liquid to be treated such as blood is taken out of the body, a causative substance or the like in the liquid to be treated is removed by a purification column, purified, and then returned. The purification column used here may also be referred to as a blood purification column. These blood purification therapies have the advantage of having fewer side effects than the treatment method in which the drug is directly administered into the patient's body. On the other hand, if a large amount of blood is taken out of the body, side effects such as a decrease in blood pressure and anemia may occur. Is required to do.
[0003]
　In order to reduce the amount of blood taken out, it is necessary to reduce the column size in the purification column, but simply reducing the column size reduces the efficiency of blood purification.
[0004]
　Therefore, so far, adsorbents / columns have been developed with the intention of suppressing the amount of liquid to be treated and achieving high adsorption performance.
[0005]
　For example, Patent Document 1 describes an invention of a column using beads as an adsorbent.
[0006]
　Patent Document 2 describes a column in which fibers are filled and arranged in the column.
[0007]
　In Patent Document 3, by using a solid fiber as an adsorbent and designing and optimizing a column, residual liquid to be treated (residual blood in the case of blood) is suppressed and the adsorption performance of the adsorbed substance is improved. It is stated that it can be done.
[0008]
　Patent Document 4 discloses a blood purification membrane in which the average roughness of the central surface of the blood contact surface in a wet state is less than a certain value.
prior art literature
Licensed Literature
[0009]
Patent Document 1: Japanese Patent Application Laid-Open No. 2016-215156
Patent Document 2: Japanese Patent Application Laid-Open No. 2009-29722
Patent Document 3: Japanese Patent Application Laid-Open No. 2017-185221
Patent Document 4: Japanese Patent Application Laid-Open No. 2005-224604
non-licensed literature
[0010]
Non-licensed Document 1: Kazuhiko Ishikiriyama et al. ; JOURNAL OF COLLOID AND INTERFACE SCIENCE, 171, 103-111, (1995)
Unlicensed Document 2: Kazuhiko Ishikiriyama et al. ; JOURNAL OF COLLOID AND INTERFACE SCIENCE, 173, 419-428, (1995) Unlicensed
Document 3: The 38th Session of Pore Size Thermometry Symposium Gist Collection 38-39
Outline of the invention
Problems to be solved by the invention
[0011]
　When reducing only the length of the column in order to reduce the size of the column, the liquid to be treated does not evenly contact the adsorbent filled in the column, and a short path is created in which the liquid to be treated flows only near the center of the shaft. It may be more likely to occur. On the other hand, when only the cross-sectional area of ​​the column is reduced, the pressure on the liquid to be treated that enters the column increases, and the pressure on the liquid to be treated that exits the column decreases. In the process of generating this pressure loss, when the liquid to be treated is blood in particular, high pressure stimulates and activates the blood cell component, which may damage the blood cell component and cause hemolysis.
[0012]
　Therefore, in order to realize a uniform flow of the liquid to be treated in the column and 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 shown in Patent Documents 1 to 3, when a low-capacity purification column having a small amount of liquid to be treated is to be produced, it is next to suppress pressure loss and obtain a purification column having excellent adsorption performance. There was a difficulty in that.
[0014]
　In Patent Document 1, when the adsorbent is bead-shaped, the surface area per volume of the adsorbent is minimized because it is spherical, and the bead diameter is reduced or the beads to be filled are reduced in order to increase the surface area per volume. If the amount is increased, the gap between the beads becomes narrower, and the pressure loss may increase.
[0015]
　Patent Document 2 describes beads, hollow fibers, and solid fibers as adsorbents, but there is a problem in securing a surface area that contributes to adsorption. Further, it is possible to increase the total surface area that contributes to adsorption by increasing the number of filled fibers by reducing the diameter of the fiber, but in this case, the gap between the adsorbents becomes narrower, so that the flow path Resistance increases. The pressure loss increases as the flow path resistance increases. Therefore, there is still a problem in achieving both low pressure loss and high adsorption performance in reducing the column size.
[0016]
　Patent Document 3 describes that it is possible to improve the flowability and reduce the 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 miniaturized as it is, it is considered difficult to achieve both high adsorption performance and low pressure loss.
[0017]
　Patent Document 4 relates to a separation membrane, and does not achieve both adsorption and suppression of hemolysis by stimulation of blood cell components.
[0018]
　Therefore, it is an object of the present invention to provide a purification column which realizes low pressure loss and has high adsorption performance while being a small purification column in which the volume of liquid to be treated is reduced in order to reduce the amount of blood taken out. do.
Means to solve problems
[0019]
　That is, the present invention is a fiber bundle containing a plurality of porous fibers that satisfy 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 surface of the porous fiber. The arithmetic mean roughness (wet Ra value) in the 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) (fiber bundle length). ) / (Length of one porous fiber), the linearity of the fiber bundle is 0.97 or more and 1.00 or less.
[0020]
　Further, in the present invention, the fiber bundle of the present invention is housed substantially parallel to the longitudinal direction of the tubular case, and a header having an inlet port and an outlet port for the liquid to be treated is provided at both ends of the tubular case, respectively. It is a purification column attached (purification column (I) of the present invention).
[0021]
　Further, in the present invention, a fiber bundle formed by bundling two or more fibers is housed substantially parallel to the longitudinal direction of the tubular case, and the inlet port and the outlet of the liquid to be treated are accommodated at both ends of the tubular case, respectively. It is a purification column to which a header having a port is attached and satisfies the following requirements (i) to (v) (purification column (II) of the present invention).
(I) Assuming that the diameter of the inscribed circle in the cross section of the fiber is Di and the diameter of the circumscribed circle is Do, the degree of deformation of the cross section of the fiber represented by Do / Di is 1.3 or more and 8.5. The following
(ii) the filling rate of the fiber in the accommodating portion is within the range of 40% or more and 73% or less
(iii) the inner diameter of the accommodating portion is 32 mm or more and 60 mm or less
(iv) (accommodated in the purification column). The linearity of the fibers represented by (the length of the fiber bundle) / (the length of one fiber contained in the purification column) is 0.97 or more and 1.00 or less
(v) the object to be treated in the container. The volume of the liquid flow path is within the range of 5 mL or more and 60 mL or less.
[0022]
　Further, the present invention is a method for producing a fiber bundle, which focuses the fibers under the conditions satisfying the following (a) and (b).
(A) The tension at the time of winding the fiber around the skein is 0.5 gf / piece or more and 10.0 gf / piece or less
. Distance from parallel movement in the vertical direction) is 0.1 mm or more and 30 mm or less.
The invention's effect
[0023]
　According to the present invention, it is possible to obtain a purification column having a low pressure loss and high adsorption performance while being a small purification column having a reduced volume of liquid to be treated in order to reduce the amount of blood taken out.
A brief description of the drawing
[0024]
FIG. 1 is a side view illustrating an embodiment of a purification column according to the present invention.
FIG. 2 is a circuit diagram relating to β2-MG clearance measurement of the purification column according to the present invention.
Embodiment for carrying out the invention
[0025]
　Hereinafter, the present invention will be described in detail.
In the present invention, "greater than or equal to" means the same as or larger than the numerical value shown therein. Further, "less than or equal to" means the same as or smaller than the numerical value shown therein.
Further, when there is no particular distinction between "fiber bundle (I) of the present invention" / "purification column (II) of the present invention" such as "fiber in the present invention", it is common to all of them. It shall be true.
[0026]
　
　The constituent material of the fiber in the present invention is not particularly limited, but a polymer material is preferably used from the viewpoint of ease of molding and cost, and for example, polymethylmethacrylate (hereinafter, PMMA). ), Polyacrylonitrile (hereinafter referred to as PAN), polysulfone, polyethersulfone, polyarylethersulfone, polypropylene, polystyrene, polycarbonate, polylactic acid, polyethylene terephthalate, cellulose, cellulose triacetate, ethylene-vinyl alcohol copolymer, poly. Caprolactam or the like is used. Further, when the fiber is used, it is preferable to contain a material having a property of adsorbing a protein or the like by a hydrophobic interaction, and examples thereof include PMMA and PAN. When used as a fiber, it is preferably used because it has a homogeneous structure, the pore size distribution can be easily controlled, and relatively sharp substance separation is possible. Further, since the amorphous polymer does not crystallize in the spinning step and the post-step, it is excellent in spinnability, continuous productivity and process moldability. In particular, since PMMA is an amorphous polymer and has high transparency, it is relatively easy to observe the internal state of the fiber, so that it is easy to evaluate the perfusion state of the liquid to be treated such as fouling, which is preferable.
[0027]
　In addition, the surface of the fiber is modified for the purpose of controlling the ligand and the charged state to improve the adsorption performance of the substance to be adsorbed, and controlling the surface properties such as the friction and biocompatibility of the membrane by the polymer / functional group. You may. Reforming refers to immobilizing a polymer or small molecule compound on the surface of a membrane. Here, the immobilized state is not particularly limited, and may be chemically bonded or may be a physical bond such as an electrostatic interaction or a hydrogen bond. The modification method is not particularly limited, but for example, by irradiating the fiber with an aqueous solution containing a polymer in contact with the fiber, a modified fiber having a hydrophilic polymer immobilized on the surface can be obtained. .. When a purification column is used for medical equipment, it can be sterilized at the same time by irradiating it with radiation.
[0028]
　Further, the fiber in the present invention preferably has a porous structure having pores inside the fiber. Further, the fiber in the fiber bundle (I) of the present invention has a porous structure having pores inside the fiber. By adopting a porous structure, the substance to be adsorbed can be adsorbed not only on the surface of the fiber but also on the pores inside the fiber, and the adsorption performance per volume is improved.
[0029]
　The average pore radius of the fiber is preferably 0.8 nm or more, more preferably 1.5 nm or more, still more preferably 2.0 nm or more, still more preferably 2.5 nm or more. On the other hand, it is preferably 90 nm or less, more preferably 55 nm or less, still more preferably 30 nm or less, still more preferably 22 nm or less. When the average pore radius is in the above-mentioned preferable range, the substance to be adsorbed is adsorbed on the surface of the fiber, and in addition, it diffuses into the inside of the fiber and is also adsorbed in the pores inside, so that the adsorption efficiency is improved.
[0030]
　For the average pore diameter, pore volume, and pore diameter distribution of fibers having a porous structure, the degree of freezing point drop due to capillary aggregation of water in the pores is determined using a differential scanning calorimeter (DSC) that can measure in a water-containing state. It can be calculated by measuring. Specifically, the adsorbent is rapidly cooled to −55 ° C., then heated to 5 ° C. at 0.3 ° C./min for measurement, and calculated from the obtained curve. For details, refer to the description of Non-Patent Document 1. Further, the i-order average pore diameter, that is, the average pore radius as referred to in the present invention is obtained from the following mathematical formula (2) of Non-Patent Document 3 based on the mathematical formula (1) described in Non-Patent Document 2. Here, the primary average pore diameter is i = 1, and this value is the average pore diameter.
[0031]
[Number 1]

[0032]
[Number 2]

[0033]
　The porous fiber in the present invention preferably has an aperture ratio of an opening on the fiber surface, that is, a surface opening ratio of 0.1% or more and 30% or less. The surface opening referred to in the present invention represents a hole or void on the surface of a porous fiber that does not include pores inside the fiber and is classified as a black part by the following measuring method. By setting the surface aperture ratio to 0.1% or more, more preferably 0.5% or more, further preferably 1% or more, still more preferably 2% or more, a flow path to the inside of the fiber can be secured and the adsorption performance can be improved. improves. Further, by setting the content to 30% or less, more preferably 25% or less, still more preferably 20% or less, still more preferably 15% or less, the smooth surface causes the components in the blood to collide with the fiber surface in the treatment of blood. Can be suppressed and hemolysis can be suppressed.
[0034]
　The fiber in the present invention preferably has a porous structure homogeneous in the cross-sectional direction. The porous fiber diffuses the substance to be adsorbed into the fiber and adsorbs the substance to be adsorbed to the pores inside the fiber. Therefore, having a homogeneous porous structure contributes to the adsorption efficiency including the inside of the fiber. be able to.
[0035]
　Here, the homogeneous porous structure means that the ratio of the average pore diameter in the region near the outer surface of the fiber to the average pore diameter in the central region of the fiber (average pore diameter in the region near the outer surface / average pore diameter in the central region) is 0. . Refers to a porous structure that is 50 times or more and 3.00 times or less. It is preferably 0.75 times or more and 2.00 times or less, and more preferably 0.85 times or more and 1.50 times or less.
[0036]
　Next, the method for determining the homogeneous structure in the present invention will be described. First, the porous fibers are sufficiently moistened and then immersed in liquid nitrogen, and the water in the pores is instantaneously frozen in liquid nitrogen. Then, the porous fiber is quickly folded, and the frozen fiber is removed in a vacuum dryer of 0.1 torr (13.3 Pa) or less in a state where the fiber cross section is exposed to obtain a dried sample. Then, by sputtering, a thin film such as platinum (Pt) or platinum-palladium (Pt-Pd) is formed on the fiber surface and used as 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, a concentric circle is drawn passing through the points that divide the line segment of this radius into five evenly lengths, and the region including the center point is set as the central region. The side close to the outer peripheral portion is defined as the region near the outer surface. The equivalent circle diameters of the holes existing in the central region and the region near the outer surface are obtained, and the average pore diameter in each region is obtained. When calculating the average pore diameter in each region, a scanning electron microscope (50,000 times) was used to arbitrarily select 20 locations in the range of 2 μm × 2 μm, and the photographs taken were measured for those containing the entire pores. The average hole diameter shall be calculated. In the measurement of the hole diameter, a transparent sheet is placed on a printed electron microscope image, and the hole portion is painted black with a black pen or the like. After that, by copying the transparent sheet to a blank sheet, the hole portion is clearly distinguished from black and the non-perforated portion is white, and the hole diameter is obtained by image analysis software.
[0037]
　In the fiber bundle (I) of the present invention, it is important that the arithmetic average 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 setting the dry Ra to 11 nm or more, preferably 12 nm or more, more preferably 13 nm or more, and further preferably 14 nm or more, unevenness is generated on the fiber surface, the flow in the vicinity of the surface pole is disturbed, and the liquid to be treated on the fiber surface. The boundary layer with the substance inside can be thinned to improve the adsorption performance. Further, by setting the thickness to 30 nm or less, preferably 28 nm or less, more preferably 26 nm or less, still more preferably 24 nm or less, the frequency of contact, collision, and rubbing between the blood cells and the fiber surface is suppressed when the liquid to be treated is blood. It is possible to suppress the release of hemoglobin inside erythrocytes into the blood (hemolysis) due to damage and activation of blood cells.
[0038]
　In the fiber of the present invention, the arithmetic average roughness (wet Ra) of the fiber surface in a wet state is preferably 12 nm or more and 40 nm or less. Further, in the fiber bundle (I) of the present invention, it is important that the arithmetic average roughness (wet Ra) of the fiber surface in the wet state of the porous fiber is 12 nm or more and 40 nm or less (requirement (C)). By setting the wet Ra to 12 nm or more, preferably 13 nm or more, more preferably 14 nm or more, and further preferably 15 nm or more, unevenness is generated on the fiber surface, the flow in the vicinity of the surface pole is disturbed, and the liquid to be treated on the fiber surface is treated. The boundary layer with the substance inside can be thinned to improve the adsorption performance. Further, by setting the thickness to 40 nm or less, preferably 38 nm or less, more preferably 36 nm or less, still more preferably 34 nm or less, the frequency of contact, collision, and rubbing between the blood cells and the fiber surface is suppressed when the liquid to be treated is blood. It is possible to suppress the release of hemoglobin inside erythrocytes into the blood (hemolysis) due to damage and activation of blood cells.
[0039]
　Further, 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 dry Ra is 1.05 or more (requirement (D)). By setting wet Ra / dry Ra to 1.05 or more, the molecular chain on the surface of the porous fiber can be sufficiently swelled when it comes into contact with the liquid. Then, the amount of useful plasma protein such as immunoglobulin is reduced, and undesired effects such as a decrease in immune function can be suppressed.
[0040]
　The solid or hollow shape of the fiber in the present invention is preferably a solid fiber. Further, it is important that the shape of the porous fiber in the fiber bundle (I) of the present invention is a solid shape (requirement (A)). In a straw-shaped hollow fiber having a cavity inside the fiber, when the liquid to be treated is passed inside and outside the fiber, a pressure difference is generated between the inside and the outside, and the pressure difference causes the liquid to be treated to stay and the non-treated liquid to stay. In the case of blood, a phenomenon called residual blood may occur inside, and the solid fiber can prevent this phenomenon.
[0041]
　The fiber in the present invention preferably has an irregular cross-sectional shape. Further, the fibers arranged on the purification column (II) of the present invention have an irregular cross-sectional shape. By forming the fiber into an irregular 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 deformation of the deformed cross section of the fiber can be expressed by the degree of deformation. The degree of deformation referred to here is expressed by the ratio of the diameters of the inscribed circle and the circumscribed circle when observing the cross section of the fiber, that is, the ratio Do / Di of the diameter Di of the inscribed circle and the diameter Do of the circumscribed circle. The value. When a fiber having an irregular cross section is adopted, the fiber bundle (I) of the present invention is preferably applied because the irritation to blood cells and the like may be greater than that of a circular fiber.
[0042]
　Here, the deformed cross section may have a shape that maintains symmetry such as line symmetry and point symmetry, or may be asymmetric. When it is judged that the irregular cross section maintains line symmetry and point symmetry, the inscribed circle is the largest circle inscribed in the contour line of the fiber in the fiber cross section, and the circumscribed circle is the fiber cross section. It is a circle circumscribing the line forming the outline of the fiber.
[0043]
　On the other hand, when it is judged that the irregular cross section has a shape that does not maintain line symmetry and point symmetry at all, the inscribed circle and the circumscribed circle are defined as follows. The inscribed circle is inscribed at least at two points with the contour line of the fiber, and exists only inside the fiber, and is the maximum that can be taken as long as the circumference of the inscribed circle and the contour line of the fiber do not intersect. A circle with a radius. The circumscribed circle is a circle that is circumscribed at at least two points on the line indicating the contour of the fiber, exists only outside the cross section of the fiber, and has the minimum radius that can be taken within the range where the circumference of the circumscribed circle and the contour of the fiber do not intersect. And.
[0044]
　The degree of deformation Do / Di of the cross section of the fiber in the present invention is preferably 1.3 or more and 8.5 or less. Further, it is important that the degree of deformation 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 setting the degree of deformation to 1.3 or more, preferably 1.5 or more, more preferably 1.8 or more, and further preferably 2.0 or more, the surface area per volume can be increased and the fibers are adsorbed. The ability to adsorb substances can be improved. On the other hand, by setting it to 8.5 or less, preferably 6.5 or less, more preferably 4.0 or less, and further preferably 3.7 or less, the breaking strength of the fiber is maintained, and the protrusions and protrusions are bent. It is possible to prevent disconnection. Further, when the undiluted spinning solution is rapidly cooled by using a gas or liquid when spinning into fibers, if the protrusions or protrusions are excessively present, the flow of wind or liquid is obstructed. As a result, the inside of the fiber is cooled slowly, so that the microstructure such as the fiber shape, pores, and surface openings tends to be uneven.
[0045]
　Examples of the fiber cross-sectional shape of the fiber having protrusions include an ellipse, an L-shape, and a V-shape in the case of two fibers. In the case of three, there are Y-shaped, T-shaped, etc. In the case of four, it looks like a cross, and in the case of five, it looks like a star. When the fiber in the present invention is formed by rapidly cooling the undiluted spinning solution with a gas or liquid, the uneven portion of the fiber is uniformly cooled and the number of protrusions is appropriately selected so as not to cause structural unevenness. do.
[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, it is possible to obtain an advantage that, for example, the protrusions and valleys just overlap each other, preventing the fibers from being excessively adhered to each other as in the case of an uneven shape, and securing a flow path for the liquid to be treated.
[0047]
　The diameter of the fiber used in the present invention, which corresponds to a circle in the cross section of the fiber, is preferably 10 μm or more and 1000 μm or less. The circle-equivalent diameter refers to the diameter when the cross-sectional area of ​​the fiber is converted into a circle. By setting the equivalent circle diameter to 10 μm or more, more preferably 20 μm or more, further preferably 30 μm or more, still more preferably 40 μm or more, the breaking strength of the fiber is improved, the fiber is less likely to be cut in the spinning process, and the productivity is improved. Excellent fibers can be obtained. In addition, since it is possible to suppress the occurrence of fiber breakage / breakage in the manufacturing process such as the column insertion process after spinning, it is also excellent in handleability. Further, the volume per surface area is appropriate, and there is no possibility that the adsorption site is saturated and the adsorption performance is drastically deteriorated even if the liquid to be treated is passed for a certain period of time. Further, by setting the thickness to 1000 μm or less, more preferably 800 μm or less, further preferably 500 μm or less, still more preferably 300 μm or less, the cooling efficiency of the fibers discharged in the spinning process is improved, and the shape of the fibers can be easily maintained. It is possible to easily maintain the degree of deformation as designed. Retaining the degree of deformity is desirable for the development of favorable adsorption performance.
[0048]
　When the fiber in the present invention is used for medical purposes, it is preferable that it can adsorb cytokines, β2-microglobulin (β2-MG), low-density lipoprotein, very low-density lipoprotein, apolipoprotein and the like as pathogenic proteins. Typical inflammatory cytokines include tumor necrosis factor α (TNFα). TNFα is a protein related to autoimmunity, and is preferably removed from the blood because its blood concentration increases in rheumatism and the like and causes inflammation, pain and the like. The adsorption performance of TNFα of the fiber in the present invention is preferably 1 μg / cm 3 or more, more preferably 15 μg / cm 3 or more, still more preferably 30 μg / cm 3 or more, still more preferably 55 μg / cm 3 or more, still more preferably 55 μg / cm 3 or more. 80 μg / cm 3 or more.
[0049]
　On the other hand, the fiber in the present invention preferably has a low adsorption amount for useful proteins such as immunoglobulin and complement. In particular, IgG, which plays a major role in immunity, is preferably not excessively adsorbed. If the amount of IgG adsorbed is too large, the subject's immunity tends to decrease when used as a purification column. Therefore, the IgG adsorption performance of the fiber in the present invention is preferably 13 mg / cm 3 or less, more preferably 9 mg / cm 3 or less, still more preferably 6 mg / cm 3 or less, still more preferably 3 mg / cm 3 or less. ..
[0050]
　 The fiber bundle
　in the present invention is preferably a multifilament in which at least a plurality of the above-mentioned fibers and at least two or more fibers are bundled. Here, the number of fibers included in the fiber bundle is appropriately selected from the shape of the tubular case, the filling rate, the fiber diameter, and the ease of arrangement. By setting the range appropriately, it is possible to prevent the fibers from being broken, bent, damaged or meandering due to contact between the fibers in the manufacturing process after being inserted into the tubular case. Further, if the number of fibers is too large, it is not preferable because it becomes difficult to insert the fiber bundle into the tubular case and the flow of the liquid to be treated deteriorates during actual use.
[0051]
　In the multifilament, a plurality of fibers may be twisted together, but by twisting, the portion where the fibers are in close contact with each other is difficult to come into contact with the liquid to be treated, and there is a possibility that a fiber surface that does not contribute to adsorption may occur. Since it is expensive, it is preferable not to twist it.
[0052]
　It is important that the fiber bundle used in the present invention has a linearity expressed by (length of fiber bundle) / (length of one fiber) of 0.97 or more and 1.00 or less (requirement (requirement (requirement)). E), (iv)). By setting the linearity of the fiber bundle to 0.97 or more, preferably 0.975 or more, more preferably 0.98 or more, and further preferably 0.99 or more, the fiber is contained in the fiber bundle in the longitudinal direction of the fiber bundle. On the other hand, the situation where the blood cells are arranged with an inclination can be reduced, the pressure loss at the time of columnarization and the collision of blood cells with the fiber surface can be suppressed, and the blood return property is improved. Further, the upper limit of the linearity ratio is 1.00 when the length of the fiber bundle and the length of one fiber are equal.
[0053]
　Here, the "length of the fiber bundle" in the definition of the linearity ratio refers to the length from one end to the other end of the fiber bundle. The "length of the fiber bundle" in the present invention is measured by using a caliper from one end to the other end of the fiber bundle at 10 points while evenly shifting the measurement points in the circumferential direction of the fiber bundle end face, and the average value is taken. It can be obtained by asking.
[0054]
　Further, the "length of one fiber" is the length of one fiber measured in a state where one fiber is taken out from the fiber bundle, and means an average value measured for any 100 fibers. ..
[0055]
　One of the problems in the purification column using fiber bundles is the adhesion between fibers. When the fibers are in close contact with each other, the liquid to be treated cannot properly flow through the gaps between the fibers, which causes problems such as a short path in the column and retention of the liquid to be treated.
[0056]
　Until now, artificial kidneys using hollow fiber membranes have existed as purification columns using fiber bundles, but these are on the outer surface of fibers mainly composed of spacer fibers in addition to the fibers having the main function. Methods have been taken to prevent the main fibers from adhering to each other by wrapping them, or to prevent the fibers from adhering to each other by applying crimp to the fibers themselves. These methods are suitable when it is necessary to flow the liquid to be treated while retaining it to some extent for substance exchange by concentration diffusion inside and outside the hollow fiber membrane, which is a function expected of the hollow fiber membrane. It can be said that this is the method.
[0057]
　On the other hand, in a purification column of a type that uses solid yarn and removes the substance to be adsorbed exclusively by adsorption as in a preferred embodiment of the present invention, it is more important to secure the adsorption area of ​​the fiber that can catch the substance to be adsorbed. Is.
[0058]
　As described above, as a result of diligent studies by the present inventor of a method for preventing adhesion between fibers and securing an adsorption area without using spacer fibers or a method such as applying crimps to the fibers, a straight line of each fiber is obtained. We found it important to ensure sex. The importance of this linearity is not limited to theoretical thinking, but the importance of this linearity was discovered for the first time by concretely measuring the length of each fiber bundle and one fiber.
[0059]
　Furthermore, maintaining this linearity can be expected to have a greater effect by using the fiber used in the present invention as a modified cross section.
[0060]
　As described above, in the conventional purification column, the linearity of each fiber is not taken into consideration, and it can be said that this is the first new achievement means set by the inventors in the present invention. Furthermore, the fact that it is important that the linearity is 0.97 or more and 1.00 or less is first discovered by the inventors by the above-mentioned measuring method.
[0061]
　
　The fiber bundle in the present invention is housed in a column having headers attached to both ends of a tubular case for use. Here, the accommodating portion refers to a volume portion partitioned by the inner space of the tubular case. The fiber bundle may partially extend from the end of the accommodating portion toward the portion partitioned by the inner space of the header.
[0062]
　In the purification column of the present invention, fiber bundles are housed substantially parallel to the longitudinal direction of the tubular case. The term "substantially parallel" is preferably parallel to the longitudinal direction of the tubular case, but it is preferable that the number of fibers having an inclination of 20 degrees or less with respect to the longitudinal direction of the tubular case is 90% or more of the total number of fibers. Further, fibers having an inclination of up to 45 degrees may be contained in the outer peripheral portion of the fiber bundle to some extent, but the number of fibers having an inclination of more than 20 degrees and 45 degrees or less with respect to the longitudinal direction of the tubular case is 10% of the total number. The following is preferable. As the shape of the fiber in the longitudinal direction when it is incorporated in the column, a straight shape, a crimped shape, a spiral shape, or the like can be considered, but a straight shape is preferable. Since the straight fiber makes it easy to secure a flow path for the liquid to be treated, it is easy to evenly distribute the liquid to be treated in the column. In addition, the flow path resistance can be suppressed, and even when a solute in the liquid to be treated adheres, a rapid increase in pressure loss can be suppressed.
[0063]
　As the shape of the case constituting the column, a tubular body having open ends at both ends is preferable. Therefore, it is preferable that the fiber bundle is housed in a tubular case. In particular, a tubular body having a perfect circular cross section is preferable. This is because the tubular case does not have corners, so that the liquid to be treated can be suppressed from staying at the corners.
[0064]
　Further, it is preferable that the tubular case is 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 having excellent 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, polyether sulfone resins, polyolefin resins, polystyrene resins, and polyvinyls. Examples include alcoholic resins and mixtures thereof. Among these, polypropylene, polystyrene, polycarbonate and derivatives thereof are preferable in terms of moldability and radiation resistance required for a tubular case. In particular, resins with excellent transparency such as polystyrene and polycarbonate are convenient for ensuring safety because the internal state can be confirmed during perfusion, for example, when the liquid to be treated is blood, and resins with excellent radiation resistance are convenient for ensuring safety, and resins with excellent radiation resistance are used during sterility. It is preferable when irradiating with radiation. The resin is processed into a cylindrical case by injection molding with a mold or cutting the material.
[0065]
　The inner diameter of the accommodating portion in the purification column of the present invention is preferably 32 mm or more and 60 mm or less. Further, it is important that the inner diameter of the accommodating portion in the purification column (II) of the present invention is 32 mm or more and 60 mm or less (requirement (iii)). By setting the inner diameter of the accommodating portion to 32 mm or more, more preferably 34 mm or more, further preferably 36 mm or more, still more preferably 38 mm or more, the flow rate per area of ​​the liquid to be treated is reduced, and the pressure loss is excessively increased or the pressure loss is excessively increased. The accompanying hemolysis can be suppressed. In addition, the tubular case can be easily gripped by the holder during actual use, and it can be dropped due to insufficient grip to prevent the tubular case from breaking or cracking. can. Further, by setting the thickness to 60 mm or less, more preferably 58 mm or less, further preferably 56 mm or less, still more preferably 55 mm or less, still more preferably 54 mm or less, the flow of the liquid to be treated does not spread to the outer peripheral portion and the fiber is not effectively used. It can be prevented from occurring.
[0066]
　The length of the accommodating portion in the purification column is preferably 100 mm or more and 1000 mm or less. Here, the accommodating portion length is the axial length of the tubular case before the header is attached. By setting the thickness to 100 mm or more, more preferably 120 mm or more, further preferably 140 mm or more, further preferably 150 mm or more, still more preferably 160 mm or more, the handleability is improved and the insertability of the fiber into the column is improved. The handleability at the time of column production can also be good. On the other hand, by setting the thickness to 1000 mm or less, more preferably 800 mm or less, further preferably 600 mm or less, further preferably 500 mm or less, still more preferably 400 mm or less, it is possible to facilitate handling when actually used as a purification column. can.
[0067]
　In the purification column of the present invention, the length of the fiber bundle / the inner diameter (L / D) of the accommodating portion is preferably 0.5 or more and 2.5 or less. By setting the content to 0.5 or more, more preferably 0.6 or more, still more preferably 0.7 or more, still more preferably 0.8 or more, a short path in the outer peripheral portion can be suppressed and the handleability is excellent. .. On the other hand, when it is 2.5 or less, more preferably 2.0 or less, further preferably 1.7 or less, still more preferably 1.4 or less, the pressure loss is excessively increased, hemolysis, and blood cell irritation are deteriorated. Can be suppressed.
[0068]
　In the purification column of the present invention, the filling rate of the fibers in the accommodating portion is preferably 40% or more and 73% or less. Further, in the purification column (II) of the present invention, the filling rate of the fibers in the accommodating portion is 40% or more and 73% or less (requirement (ii)). By setting the filling rate to 40% or more, more preferably 45% or more, further preferably 50% or more, still more preferably 55% or more, the fibers in the tubular case are less likely to be biased, and the liquid to be treated in the purification column is not easily biased. It is possible to prevent uneven flow. Further, by setting it to 73% or less, more preferably 71% or less, further preferably 70% or less, further preferably 69% or less, still more preferably 67% or less, the insertability into the tubular case is good. can do.
[0069]
　The filling factor is the capacity of the accommodating portion (Vc) / the volume of fibers in the accommodating portion (Vf). The capacity of the accommodating portion is the volume of the inner empty portion of the tubular case calculated from the cross-sectional area of ​​the accommodating portion and the length of the accommodating portion. The fiber volume in the accommodating portion is calculated from the fiber cross-sectional area, the accommodating portion length and the number of fibers. Specifically, it is expressed by the following formula.
Vc = cross-sectional area of ​​accommodating portion × length of accommodating portion
Vf = cross-sectional area of ​​fibers × length of accommodating portion × number of fibers
Filling rate = Vf / Vc × 100 (%)… (formula).
[0070]
　The cross-sectional area of ​​the accommodating portion shall be the cross-sectional area at the center of the tubular case if the tubular case has a tapered structure that expands in diameter as it approaches both ends. Further, regarding Vf, when a spacer fiber or the like for preventing the fibers from adhering to each other is used in the tubular case, the volume of the spacer fiber is also included.
[0071]
　In the purification column of the present invention, the volume of the flow path of the liquid to be treated in the accommodating portion is preferably 5 mL or more and 60 mL or less. Further, in the purification column (II) of the present invention, the capacity of the flow path of the liquid to be treated in the accommodating portion is 5 mL or more and 60 mL or less (requirement (v)). The capacity of the flow path of the liquid to be treated in the accommodating portion refers to the portion of the accommodating portion of the purification column minus the fiber volume, and is expressed as follows.
The volume (mL) = Vc-Vf fiber volume of the flow path of the liquid to be treated in
the accommodating portion is the length of the fiber bundle arranged in the accommodating portion in the total cross-sectional area of ​​the fibers calculated according to the above-mentioned method for measuring the fiber diameter. It can be calculated by multiplying by.
[0072]
　By setting the volume of the flow path of the liquid to be treated in the accommodating portion to 5 mL or more, more preferably 10 mL or more, further preferably 15 mL or more, still more preferably 20 mL or more, the substance to be adsorbed can be efficiently removed in a predetermined time. Can be done. On the other hand, if it is 60 mL or less, more preferably 55 mL or less, further preferably 50 mL or less, further preferably 45 mL or less, still more preferably 40 mL or less, there is a risk of causing a decrease in blood pressure / anemia without taking a large amount of blood out of the body. A low purification column can be obtained.
[0073]
　Further, in the present invention, the volume of the flow path of the liquid to be treated in the entire purification column including the accommodating portion is preferably 10 mL or more and 70 mL or less. By setting the amount to 10 mL or more, more preferably 15 mL or more, further preferably 20 mL or more, still more preferably 25 mL or more, the distance and space from the inlet port of the liquid to be treated to the accommodating portion are secured, and the liquid to be treated linearly. It can be prevented from flowing and can be evenly diffused and passed through the header. On the other hand, the amount of blood taken out can be reduced by using 70 mL or less, more preferably 60 mL or less, still more preferably 50 mL or less, still more preferably 40 mL or less.
[0074]
　In the purification column of the present invention, it is preferable that the circular equivalent diameter of the flow path of the liquid to be treated is 20 μm or more and 100 μm or less. By setting the thickness to 20 μm or more, more preferably 25 μm or more, further preferably 30 μm or more, still more preferably 35 μm or more, it is possible to secure a flow path of the liquid to be treated and suppress an increase in pressure loss during liquid passage. On the other hand, by setting it to 100 μm or less, more preferably 90 μm or less, further preferably 80 μm or less, still more preferably 70 μm or less, it is possible to prevent the flow of the liquid to be treated from being biased to a specific flow path and not spreading over the entire column, and it is porous. The fiber surface and the liquid to be treated can be efficiently brought into contact with each other.
[0075]
　Here, the circle-equivalent diameter of the flow path of the liquid to be treated can be calculated by using the occupied portion of the liquid to be treated and the immersion side length in the cross-sectional area. The immersion side length refers to the length of the circumference in which the liquid to be treated is in contact with the solid wall in the flow path.
Circular equivalent diameter (μm) of the flow path of the liquid to be treated = 4 × Occupied liquid to be treated in cross-sectional area (cm 2 ) / Immersion side length (cm) × Occupied liquid to be treated in 10000 cross-
sectional area (cm 2 ) = Column cross-sectional area-total cross-sectional area of ​​fibers
Immersion side length (cm) = case inner diameter x π + outer peripheral length of fibers x number of fibers ... (Equation).
[0076]
　FIG. 1 shows a side view illustrating an embodiment of the purification column according to the present invention. In this embodiment, the purification column 1 is provided with a fiber bundle as an adsorbent 5 in a column partitioned by at least a header 2, a distribution plate 3, and a tubular case 4. The header 2 is provided with a port that serves as an inlet and an outlet for the liquid to be treated. In FIG. 1, a cap for sealing the port portion is provided.
[0077]
　The purification column of the present invention has a wide variety of uses, and can be mainly used for separating substances to be adsorbed from various liquids and gases. Especially in medical applications, pathogenic proteins, bacteria, viruses, endotoxins, sugar chains, autoantibodies, immune complexes, free light chains, potassium, bilirubin, bile acids, creatinine, phosphorus compounds, drugs, etc. from blood, plasma, and body fluids. It is suitably used for removing blood plasma. Pathogenic proteins include cytokines, β2-microglobulin (β2-MG), low-density lipoprotein, very low-density lipoprotein, apolipoprotein and the like. In addition, when used for water treatment, it is suitably used for removing humic acid, metal corrosive substances, and the like.
[0078]
　In the purification column of the present invention, it is preferable that the pressure loss when bovine blood is flowed at a flow rate of 200 mL / min for 1 hour is 1 kPa or more and 20 kPa or less. By setting the content to 1 kPa or more, more preferably 1.5 kPa or more, still more preferably 2 kPa or more, still more preferably 2.5 kPa or more, proteins are easily transferred to the inside of the porous fiber and the adsorption performance is improved. Further, by setting the content to 20 kPa or less, more preferably 10 kPa or less, further preferably 9 kPa or less, still more preferably 8 kPa or less, still more preferably 7 kPa or less, the shear stress applied to the blood cells is prevented from increasing and causing hemolysis. Can be done. The pressure loss can be controlled by adjusting the filling rate of fibers in the column, the inner diameter of the tubular case, the fiber diameter, the number of fibers, and the like. The detailed measurement method of the pressure loss will be described later, but it is calculated using the following formula.
Pressure loss = inlet pressure of circuit with column-outlet pressure of circuit with column- (inlet pressure of circuit only-outlet pressure of circuit only) ... (Equation).
[0079]
　In the purification column of the present invention, the increase in hemolysis rate when bovine blood is flowed at a flow rate of 400 mL / min for 4 hours is preferably 1.0 or less. By 1.0 or less, more preferably 0.9 or less, still more preferably 0.8 or less, still more preferably 0.7 or less, still more preferably 0.6 or less, hemolysis occurs when blood is taken out from the patient. Can be reduced. The increase in hemolysis rate is expressed by the following formula.
Increased hemolysis rate = hemolysis rate of bovine blood after circulation-hemolysis rate of bovine blood before circulation
The detailed measurement method of hemolysis rate will be described later, but the hemoglobin (Hb) concentration is measured using a measurement kit or the like. , Calculate using the following formula.
Hemolysis rate (%) = plasma hemoglobin concentration (mg / dL) / total hemoglobin concentration (mg / dL) × 100… (formula).
[0080]
　Targets for adsorption and removal of the purification column of the present invention include β2-MG, which is a causative protein of dialysis amyloidosis, which is a dialysis complication. 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 flowed at a flow rate of 200 mL / min for 1 hour. By setting it to 35 mL / min or more, more preferably 40 mL / min or more, further preferably 50 mL / min or more, still more preferably 60 mL / min or more, it has sufficient β2-MG adsorption ability to obtain an excellent therapeutic effect. The column can be produced. On the other hand, when the content is 120 mL / min or less, the adhesion of other useful substances in blood can be suppressed. The detailed measurement method of 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 relating to β2-MG clearance measurement of the purification column according to the present invention. In this circuit 6, a pump 7 for circulating a 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 for keeping the temperature constant. A disposal beaker 11 for storing bovine blood for clearance after passing the purification column liquid is also provided.
[0082]
　The purification column of the present invention has a clearance / storage capacity, which is a value obtained by dividing the β2-MG clearance when bovine blood is flowed at a flow rate of 200 mL / min for 1 hour by the volume of the flow path of the liquid to be treated in the purification column. It is also preferable that it is 1.0 or more. Since the clearance / storage capacity represents the adsorption performance per amount of blood taken out, the higher the value, the higher the therapeutic effect can be exhibited while suppressing the occurrence of anemia during use.
[0083]
　
　In the production of the fiber in the present invention, the viscosity of the spinning stock solution is preferably 10 poise (1 Pa · sec) or more and 100,000 poise (10,000 Pa · sec) or less. The fluidity of the undiluted solution can be increased by setting the fluidity to 10 poise (1 Pa · sec) or more, more preferably 90 poise (9 Pa · sec) or more, further preferably 400 poise (40 Pa · sec) or more, still more preferably 800 poise (80 Pa · sec) or more. It becomes easy to maintain the desired shape in an appropriate manner. On the other hand, by setting the pressure to 100,000 pose (10,000 Pa · sec) or less, more preferably 50,000 pose (5,000 Pa · sec) or less, the pressure loss at the time of discharging the undiluted solution does not increase, and the stability of discharge is maintained. In addition, the undiluted solution can be easily mixed.
[0084]
　The viscosity is measured by the falling ball method in a constant temperature bath set to the spinning temperature according to JIS Z 8803: 2011. Specifically, it is obtained by filling a viscosity tube having an inner diameter of 40 mm with a spinning stock solution, dropping a steel ball having a diameter of 2 mm (material is SUS316) into the stock solution, and measuring the time required for dropping 50 mm. The temperature at the time of measurement is 92 ° C.
[0085]
　In the above range, a spinning stock solution in which a polymer is dissolved in a solvent is prepared. At this time, the lower the concentration of the undiluted polymer (concentration of the substance excluding the solvent in the undiluted solution), the larger the pore diameter of the fiber. It is possible to control. From this point of view, the undiluted polymer concentration in the present invention is preferably 30% by mass or less, more preferably 27% by mass or less, still more preferably 24% by mass or less.
[0086]
　In addition, the pore diameter and the amount of pores can be controlled by using a polymer having a negatively charged group. When, for example, a polymer having methacrylic sulfonic acid parastyrene sulfonic acid is used as the negative charging group, the proportion of the polymer having methacrylic sulfonic acid parastyrene sulfonic acid present in all the polymers is preferably 10 mol% or less.
[0087]
　In order to produce a fiber having a modified cross-sectional shape as the fiber in the present invention, it is preferable to control the shape of the discharge port of the spinneret in addition to the composition of the undiluted spinning solution and the device in the drywall section. For example, it is preferable that the mouthpiece is composed of a center circle, a slit, and a circle at the tip of the slit, and the diameter of the center circle, the width of the slit portion, the length of the slit portion, and the diameter of the tip circle are appropriately designed. With a mouthpiece having such a preferable shape, the cross-sectional area of ​​the mouthpiece discharge port is appropriate, so that the draft in the dry type portion does not become too large, and the fiber diameter and irregular shape, which are called draw resonance, are less likely to occur. , Easy to spin.
[0088]
　As the spinning method for obtaining the fiber in the present invention, either melt spinning or solution spinning may be used. In solution spinning, fibers are obtained by passing the undiluted solution through a dry air portion for a certain distance using a mouthpiece and then discharging it into a coagulation bath composed of a poor solvent such as water or a non-solvent.
[0089]
　The production of porous fibers having a porous structure is not limited to the production methods of heat-induced phase separation and non-solvent-induced phase separation, but in non-solvent-induced phase separation, the solvent is rapidly removed during coagulation bath immersion. , It is preferable because it is relatively easy to obtain a porous shape. Further, the dry / wet portion may be any of a dry type, a wet type, and a dry / wet portion, but the dry / wet portion is particularly preferable because the porous structure of the fiber surface can be precisely controlled by the dry / wet portion condition. Although the detailed mechanism is not clear, it is possible to control the degree of unevenness and surface roughness of the surface of the porous fiber by adjusting the cold air temperature and the dew point. For example, by increasing the cooling air speed to increase the cooling efficiency, the surface aperture ratio of the fiber and the pore diameter in the vicinity of the outer peripheral portion of the fiber can be increased.
[0090]
　The draft ratio at the time of ejection 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 rate to the rate at which the undiluted spinning solution exits the spinneret. By setting the draft ratio to 1.5 or more, more preferably 3 or more, or 30 or less, it can be stretched under an appropriate tension, and it can be prevented to some extent from being fanned by cold air or outside air. Further, under the spinning condition in which the drywall portion is present, the pores of the fiber are stretched to form an elliptical shape, so that the surface area per space is smaller than that of the spherical pores. As a result, it is possible to obtain a fiber having both a separation amount and sharpness of separability.
[0091]
　In solution spinning, the undiluted spinning solution discharged from the mouthpiece is coagulated in a coagulation bath. The coagulation bath generally consists of a coagulant such as water or alcohol, or a mixture with a solvent constituting the spinning stock solution. Water is generally selected from the viewpoints of ease of wastewater treatment, safety in the living body at the time of manufacture, and risk of ignition / leakage. Further, the pore diameter can be changed by controlling the temperature of the coagulation bath. Since the pore diameter is affected by the temperature at the time of phase separation and the environment around the polymer, the temperature of the coagulation bath is also appropriately selected. Generally, the pore diameter can be increased by increasing the coagulation bath temperature. Although this mechanism is not exactly clear, it is thought that due to the competitive reaction between desolvation from the undiluted solution and coagulation shrinkage, desolvation is rapid in a high-temperature bath, and the inside of the fiber is solidified and fixed before shrinking. Be done. For example, when the fiber contains PMMA, the coagulation bath temperature is preferably 90 ° C. or lower, more preferably 75 ° C. or lower, and particularly preferably 65 ° C. or lower. When the upper limit of the coagulation bath temperature is in the above-mentioned preferable range, the pore diameter does not become excessive, so that the pore specific surface area does not decrease, the strong elongation does not decrease, and the non-specific adsorption does not increase. The lower limit of the coagulation bath temperature is preferably 5 ° C. or higher, more preferably 20 ° C. or higher. When the lower limit of the coagulation bath temperature is in the above-mentioned preferable range, the pore diameter does not shrink too much, and the substance to be adsorbed tends to diffuse into the pores.
[0092]
　The fibers are then washed to remove any solvent adhering to the solidified fibers. The means for washing the fibers is not particularly limited, but a method in which the fibers are passed through a bath filled with water (referred to as a water washing bath) is preferably used. As for the temperature of water in the washing bath, if the washing temperature is too low, the washing effect may be insufficient, and if the washing temperature is too high, water may not be used as a washing liquid. Further, it is preferably determined according to the properties of the polymer constituting the fiber. Considering the cleaning efficiency, for example, in the case of a fiber containing PMMA, it is preferably 30 ° C. or higher and 50 ° C. or lower. Here, the time of immersion in the washing bath is also appropriately selected depending on the fiber diameter and the spinning speed. If the cleaning step is insufficient and the residual amount of the solvent is large, the fiber structure may be deteriorated and the handling after winding may be deteriorated. Therefore, sufficient cleaning is preferable. Further, when it is necessary to apply a pore-forming agent or a modifier to the fiber to some extent, excessive cleaning is not preferable.
[0093]
　Further, in order to maintain the pore diameter of the pores after washing with water, a step of imparting a moisturizing component to the fibers may be added. The moisturizing component referred to here is a component capable of maintaining the humidity of the fiber or a component capable of preventing a decrease in the humidity of the fiber in the air. Typical examples of moisturizing ingredients include glycerin and its aqueous solution.
[0094]
　After washing with water and adding the moisturizing component, it is possible to pass the process of a bath (called a heat treatment bath) filled with a heated aqueous solution of the moisturizing component in order to improve the dimensional stability of the highly shrinkable fiber. The heat treatment bath is filled with an aqueous solution of a heated moisturizing component, and when the fibers pass through this heat treatment bath, they are subjected to thermal action and shrink, and the fibers are less likely to shrink in the subsequent steps, forming a fiber structure. It can be stabilized. If the fiber structure is not stabilized, the fibers cause anisotropic shrinkage between the time of manufacture and the actual use, and the arrangement is different from that at the time of manufacture, resulting in uneven flow and adsorption performance. It is not preferable because the decrease in the amount of fiber is observed. The heat treatment temperature at this time varies depending on the fiber material, but in the case of fibers containing PMMA, it is preferably set to 50 ° C. or higher, more preferably 80 ° C. or higher, still more preferably 95 ° C. or higher, still more preferably 97 ° C. or higher. Acrylic.
[0095]
　After that, it is preferable that the fibers are introduced into the winding portion via a tension control mechanism such as a dancer roll, so that the fibers are smoothly wound while maintaining a constant tension. The tension control mechanism is not limited to the dancer roll, and may be any mechanism such as two or more drive rolls, a roll having irregularities in the circumferential direction, or the like, which fluctuates / relaxes the tension applied to the fibers.
[0096]
　In the method for producing a fiber bundle of the present invention, it is important that the tension at the time of winding is 0.5 g / piece or more and 10.0 g / piece or less (requirement (a)). 0.5 g / piece or more, more preferably 0.9 g / piece or more, still more preferably 1.0 g / piece or more, still more preferably 1.3 g / piece or more, still more preferably 1.5 g / piece or more, still more preferably. By setting the number to 1.7 / piece or more, it is possible to prevent the fibers from swelling and meandering during winding. Further, the amount of the fiber contained in the fiber bundle is set to 10.0 g / piece or less, more preferably 8.0 g / piece or less, further preferably 5.0 g / piece or less, still more preferably 3.0 g / piece or less. Brittle fracture can be prevented. When the fiber is plastically deformed, it does not return to its original length even after being released from tension. Therefore, it is preferable to keep the tension applied within the above range for the fiber having a small elastic deformation region. In addition, by winding the fibers together in an appropriate number, it is possible to prevent deformation while aligning the fibers (a plurality of fibers are called tow). By doing so, by dispersing the tension in a plurality of fibers, the preferable effect in the above range can be stably obtained without concentrating the force on one fiber. In the purification column of the present invention, since the linearity of the fibers in the fiber bundle cannot be enhanced in the step after winding, it is extremely important to apply tension before winding.
[0097]
　For winding, a skein (reel) is used because the meandering of the fibers can be suppressed. As the skein to be used, various shapes can be adopted, but a polygonal shape is preferable.
[0098]
　Before the fibers are wound around the skein, they reciprocate at a predetermined speed in the direction perpendicular to the skein axis via the traverse mechanism, and the fiber bundles are wound evenly without unevenness. Here, if the method is to wind the fiber bundle uniformly without unevenness, the fibers may be moved with respect to the skein by a guide or a roller in the traverse mechanism, or the skein itself may be translated.
[0099]
　In the method for producing a fiber bundle of the present invention, it is important that the traverse movement distance (distance of translation in the vertical direction from the traveling direction of the fiber) is 0.1 mm or more and 30 mm or less in the time for one rotation of the skein. There is (requirement (b)). By setting the thickness to 0.1 mm or more, more preferably 0.5 mm or more, still more preferably 1.0 mm or more, still more preferably 1.3 mm or more, it is possible to prevent the arrangement of fibers in the fiber bundle from becoming coarse and dense, and to make a perfect circle. It is possible to obtain a fiber bundle having a shape close to that of. Further, by setting the thickness to 30 mm or less, more preferably 25.0 mm or less, further preferably 20.0 mm or less, still more preferably 15.0 mm or less, still more preferably 10.0 mm or less, the fiber when the movement direction of the traverse is switched. It is possible to reduce the force applied to the fiber, reduce fiber breakage, breakage, and derailment from the traverse roller, and further prevent the fiber from meandering in the fiber bundle and complicating the flow path of the liquid to be treated.
[0100]
　Further, when a plurality of fibers are wound together, it is preferable to set the traverse movement distance so that the tows do not stack after one rotation and are in contact with each other sideways without any gap. The traverse movement distance when the skein makes one round rotation may be a constant value as long as it is within the above range, or may be changed during winding.
[0101]
　Further, it is preferable to change the traverse stroke during winding so as to match the final fiber bundle shape. The traverse stroke is the maximum distance that the traverse roller moves in the direction perpendicular to the skein axis, and the fibers repeat reciprocating motion within the stroke via the traverse mechanism. When focusing the fiber bundles 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 early stage, middle stage, and final stage of winding with traverse ( Requirement (c)). Here, "=" means that they are equal at the level of 1 mm, and the relationship between large and small means that there is a difference of 1 mm or more. By making it large in the middle stage forming the central portion of the above, small again in the final stage, and equal to the initial stage, a fiber bundle having a cross-sectional shape close to a perfect circle can be obtained.
[0102]
　In addition, a program may be set up to continuously change the traverse during winding, but as a result of diligent studies, it was found that it is preferable to change the traverse stroke discontinuously. Specifically, it is preferable that the number of traverse stroke changes is 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 traverse is the period until the (traverse stroke change count / 2-1) th change is made, and the middle term is the period from the (traverse stroke change count / 2-1) th change (traverse stroke change). The number of times / 2 + 1) is the period until the third change is made, 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 step by step, the toe slips at the point where the movement direction of the traverse changes (when it is made into a fiber bundle, it constitutes the outer peripheral part thereof), and the fibers meander in the obtained fiber bundle. Can be suppressed.
[0103]
　The number of traverse stroke changes is preferably 4 or more and 12 or less. By setting the number of times to 4 or more, the cross section of the obtained fiber bundle can be made into a shape close to a perfect circle. Further, by setting the number of times to 12 or less, in addition to the above-mentioned slip / meandering suppressing effect, it can be carried out by a simple program and can be manufactured relatively easily.
[0104]
　After this, the fiber bundle is cut out from the skein and inserted into the tubular case. As a method of fixing the fiber bundle end portion in the tubular case, there is also a method of arranging a mesh and a method of fixing with a resin to communicate the partition wall and providing a hole penetrating the inside and outside of the tubular case. Here, the through hole is an opening that communicates with the fiber of the partition wall portion in the longitudinal direction. In order to form a through hole, a method of inserting a small pin-shaped cylinder into the end face of the fiber bundle and then pouring the resin near the end face to perform potting can be mentioned. After the resin has solidified, both ends are cut with a cutter or the like to remove the portion where the fiber is blocked by the resin, and if the pin-shaped cylinder is removed, an opening of a through hole is formed at the end of the pot layer. Will be done. However, compared to the case of using the distribution plate described later, in addition to complicating the process, retention of the liquid to be treated and turbulent flow generally occur, making it difficult to control the flowability into the purification column. There is a risk. On the other hand, the method of arranging the mesh is more preferable because the process is easier than the method of forming the partition wall and the dispersibility of the liquid in the purification column is high.
[0105]
　Further, for the purpose of further enhancing 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 provided. The distribution plate has a structure in which a convex portion is inserted into the fiber bundle and an opening structure in which the protrusion is partitioned with respect to the flow direction. In the purification column according to the present invention, a distribution plate is arranged at least on one end surface side, and has a plurality of openings through which the liquid to be treated can communicate, a support, and a convex portion extending from the support to the fiber side. However, it is preferable that 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, it is possible to control the flow path resistance with respect to the flow direction so as to apply an inclination from the originally easy-flowing portion to the difficult-flowing portion. As a result, the flow of the liquid to be treated can be made uniform and the 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.
Example
[0107]
　An example of the embodiment of the present invention is shown in the following examples.
[0108]
　[Measurement method]
　(1) Surface aperture ratio
　of fiber The fiber to be evaluated was fixed on a substrate with double-sided tape. The morphology was observed in a wet state with an atomic force microscope SPI3800 (manufactured by Seiko Instruments). The observation mode was DMF mode, the observation field of view was 3 μm × 3 μm, and all 10 fields of view were measured. The pixel setting for observation was performed at 512 × 512 pixels or more. The obtained AFM image was analyzed using software attached to AFM manufactured by Seiko Instruments. The image is binarized according to "Automatic threshold selection method based on discrimination and minimum squared criteria" (Nobuyuki Otsu, IEICE Journal, 63, p349-356 (1980)), and the unevenness of the film surface is uneven. Information was extracted. After binarization, the area ratio of the black part of the binarized component was calculated as the surface aperture ratio by image analysis.
[0109]
　(2) The dry Ra value
　fiber was sufficiently moistened and then immersed in liquid nitrogen, and the water in the pores was instantaneously frozen in liquid nitrogen. Then, the water frozen in a vacuum dryer of 0.1 torr (13.3 Pa) or less was removed to obtain a dried sample. The dried 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 with a scanning probe microscope (NanoScope V Dimension Icon manufactured by Bruker). In the measurement of the contact surface, the measurement was performed excluding the surface opening. The observation mode was peak for tapping, the cantilever was SiN cantilever, and the observation field of view was 3 μm × 3 μm. The probe was scanned so that the vicinity of the apex of the fixed porous fiber was substantially perpendicular to the longitudinal direction of the fiber. Three fibers were arbitrarily selected for one measurement target fiber, and one place was observed for each fiber. The dry Ra value of the fiber was calculated by the arithmetic mean of each measured value.
[0110]
　(3) Wet Ra value
　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 with a scanning probe microscope (NanoScope V Dimension FastScan Bio manufactured by Bruker). Three fibers were arbitrarily selected for one measurement target fiber, and one place was observed for each fiber. The wet Ra value of the fiber was calculated by the arithmetic mean of each measured value.
[0111]
　(4) Degree of Deformity Both ends of the fiber to be measured were fixed with a tension of
　0.1 g / mm 2 applied, and cut at random positions. The cut surface was magnified and photographed with an optical microscope (DIGITAL MICROSCOPE DG-2 manufactured by SCARA Co., Ltd.). At the time of shooting, the scale was also shot at the same magnification. After digitizing the image, the diameter Do of the circumscribed circle and the diameter Di of the inscribed circle in the cross section of the fiber were measured using image analysis software (SCARA "Micro Machine" ver. 1.04). Then, the degree of deformation of each fiber was calculated by the following equation.
Degree of variant = Do / Di
This measurement was performed at 30 points, the values ​​were averaged, and the value rounded to the third decimal place was taken as the degree of variant.
[0112]
　(5) Circle-equivalent diameter Both ends of the fiber to be measured were fixed and cut under a tension of
　0.01 to 0.10 g / mm 2 . The cut surface was magnified with an optical microscope and photographed. At that time, the scale was also photographed at the same magnification. After digitizing the image, image analysis software (SCARA Co., Ltd. "Micro Measure" ver. 1.04) is used to plot the outer peripheral portion of the cross section of the fiber, connect those points on the software, and cross-sectional area. S was calculated, and the circle-equivalent diameter of each opening was calculated by the following formula.
The diameter equivalent to the circle in the cross section of the fiber = 2 × (S / 2π)
The average of the measured values ​​at 30 points was calculated and rounded off to the first decimal place.
[0113]
　(6) Length
　of one fiber One end of one fiber is fixed with tape or the like and lowered vertically, and a weight of 10 g per fiber cross-sectional area (mm 2 ) is given to the other end to make the fiber linear. The total length at the time of becoming was measured promptly. This measurement was performed on 100 arbitrarily selected fibers, and the average value was calculated. For example, when the length of one fiber actually used in the measurement of 1 is obtained as a value 1 mm or more shorter than the "length of the fiber bundle" which is the average value of any 10 points, the fiber 1 is used. Since the book is considered to have been cut in the fiber bundle or the fiber end was damaged and shortened after the manufacturing process, the data is not included in the population of 100 fibers and is different. Fiber samples are sorted and used for measurement.
[0114]
　(7) Adsorption performance of TNFα and IgG To a
　commercially available human serum (manufactured by Cosmobio), a commercially available human recombinant TNFα (manufactured by R & D) was added 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 Gleiner), 0.0142 cm 3 of fiber was added thereto, and the mixture was shaken left and right at 37 ° C. for 4 hours at a shaking rate of 30 ± 1 reciprocating / min. .. Serum before and after shaking was collected, and the concentration of TNFα was quantified by the ELISA method and the concentration of IgG was quantified by the immunoturbidimetric method. Each adsorption performance was calculated from the following formula.
Adsorption performance of TNFα (μg / cm 3 ) = (C1-C2) × 6 / 0.0142
Adsorption performance of IgG (mg / cm 3 ) = (C3-C4) × 6 / 0.0142
Here,
C1: TNFα Pre-shake concentration (μg / mL)
C2: TNFα post-shake concentration (μg / mL)
C3: IgG pre-shake concentration (mg / mL)
C4: IgG post-shake concentration (mg / mL).
[0115]
　(8) β2-MG clearance of the purification column The
　bovine blood to which disodium ethylenediaminetetraacetate was added was adjusted so that the hematocrit was 30 ± 3% and the total protein amount was 6.5 ± 0.5 g / dL. Bovine blood within 5 days after blood collection was used. For such bovine blood, 1.2 L thereof was divided for circulation and 1.2 L for clearance measurement. Next, it was added to bovine blood for clearance measurement so that the β2-MG concentration became 1 mg / L, and the mixture was stirred.
A blood circuit and a pump were set so that bovine blood could circulate, and a purification column was connected. The blood circuit inlet is placed in a circulation beaker containing 1.2 L (37 ° C) of bovine blood adjusted as described above, the pump is started with a flow rate of 200 mL / min, and the bovine blood discharged from the blood circuit outlet. Was discarded for 90 seconds, and the blood circuit outlet was immediately inserted into a circulation beaker to put it in a circulating state. After circulating for 1 hour, the pump was stopped. Next, the blood circuit inlet was placed in the bovine blood for clearance measurement adjusted above, and the blood circuit outlet was placed in a waste beaker. The flow rate was set to 200 mL / min, and 10 mL was collected from bovine blood (37 ° C.) for clearance measurement 4 minutes after the pump was started, and used as a Bi solution. After 4 minutes and 50 seconds had passed from the start, 10 mL of the sample flowing from the blood circuit outlet was collected and used as Bo solution. Then, the Bi solution and the Bo solution were centrifuged, and bovine plasma in the supernatant portion was collected. These samples were stored in a freezer below −20 ° C.
The clearance was calculated from the β2-MG concentration of each liquid 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 for clearance measurement.
[0116]
　(9) Pressure loss
　In the β2-MG clearance measurement of (8) above, the pressure difference between the inlet (Bi) and the outlet (Bo) 4 minutes after passing bovine blood for clearance measurement was measured. Further, the pressure difference between Bi and Bo was measured under the same conditions only for the circuit without connecting the purification column. The pressure loss was calculated by the following formula.
Pressure loss = Bi when column is connected-Bo when column is connected- (Bi when circuit only is connected-Bo when circuit only is connected) ... (Equation).
[0117]
　(10) Hemolysis rate
　Bovine blood prepared in the same manner as in (8) above and a blood circuit set 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 bovine blood at the start of circulation and bovine blood 4 hours after 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, manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.). Using the same measurement kit, the total hemoglobin concentration of bovine blood collected at the start was also measured, and the hemolysis rate was calculated from the following formula.
Hemolysis rate (%) = plasma hemoglobin concentration (mg / dL) / total hemoglobin concentration (mg / dL) × 100
Further, the increase in hemolysis rate was calculated using the following formula.
Increased hemolysis rate = hemolysis rate of bovine blood after circulation-hemolysis rate of bovine blood before circulation ... (Equation).
[0118]
　[Example 1]
　(Preparation of fiber bundle of PMMA)
　Syndiotactic PMMA (hereinafter, syn-PMMA) having a mass average molecular weight of 400,000 is 31.7 parts by mass, and syn-PMMA having a mass average molecular weight of 1.4 million is 31. 2.0 parts by mass, 16.7 parts by mass of isotactic PMMA (hereinafter, iso-PMMA) having a mass average molecular weight of 500,000, and a PMMA copolymer 20 having a molecular weight of 300,000 containing 1.5 mol% of sodium parastyrene sulfonic acid. A mass portion was mixed with 376 parts by mass of dimethyl sulfoxide and stirred at 110 ° C. for 8 hours to prepare a spinning stock solution. The viscosity of the obtained spinning stock solution at 92 ° C. was 1,880 poise (188 Pa · s). The obtained undiluted spinning solution is discharged from two types of caps having differently shaped discharge holes at a speed of 1.1 g / min, and after running the drywall part by 380 mm, it is guided to a coagulation bath and passed through the bath. rice field. The temperature of the atmosphere of the drywall was 15 ° C., and cold air having a dew point of 12 ° C. was applied perpendicularly to the fibers. Water was used for the coagulation bath, and the water temperature (coagulation bath temperature) was 42.5 ° C. After washing each fiber with water, it is guided to a bathtub consisting of an aqueous solution containing 70% by mass of glycerin as a moisturizer, and then passed through a heat treatment bath having a temperature of 84 ° C. to relieve residual stress, and then excess glycerin is scraped. It was removed with a skein and wound at 45 m / min with a skein. The tension at the time of winding and the traverse movement distance per lap were carried out under the conditions shown in Table 1. The number of traverse stroke changes was set to 6. In this way, a fiber bundle having 136,000 fibers including porous fibers having two kinds of irregular cross-sectional shapes was obtained.
[0119]
　In the porous fiber, the average pore radius is in 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 is in the range of 0.85 to 1.50, and the opening of the fiber surface. The aperture ratio was in the range of 2 to 15%.
[0120]
　(Preparation of purification column)
　A purification column was prepared using the obtained fiber bundle. The fiber bundle is inserted into a tubular case having a housing portion length of 42 mm and an inner diameter of the housing portion of 52 mm, and the excess is cut while leaving a part of the fiber bundle protruding from the tubular case, in the longitudinal direction of the tubular case. Contained almost in parallel. Furthermore, distribution plates and mesh headers were attached to both ends of the tubular case to form columns. The distribution plate was provided with a convex portion of a double annulus and had a shape of being evenly distributed in 9 sections in a circumferential shape. The area ratio of the cross section of the flow path excluding the columns of the distribution plate was about 60%. The glycerin remaining on the porous fibers after column formation was washed with water, the inside of the column was filled with water, and then sterilized by irradiating with γ-rays of 25 kGy.
[0121]
　[Example 2]
　A purification column was produced in the same manner as in Example 1 except that the discharge rate of the undiluted spinning solution was changed to 1.2 g / min to make the diameter equivalent to the circle of the fiber 117 μm. In the porous fiber, the average pore radius is in 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 is in the range of 0.85 to 1.50, and the opening of the fiber surface. The aperture ratio was in the range of 2 to 15%. Table 1 shows the results of various measurements.
[0122]
　[Example 3]
　By changing the discharge rate of the undiluted spinning solution to 1.0 g / min, the diameter equivalent to a circle of fibers is 110 μm, the number of fibers in the fiber bundle is 83,000, and the length of the accommodation portion of the tubular case is 55 mm. A purification column was produced in the same manner as in Example 1 except that the inner diameter of the accommodating portion was changed to 41 mm. In the porous fiber, the average pore radius is in 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 is in the range of 0.85 to 1.50, and the opening of the fiber surface. The aperture ratio was in the 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 at the time of winding was changed to 1.8 gf / piece and the traverse movement distance per rotation of the skein was changed to 1.3 mm. In the porous fiber, the average pore radius is in 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 is in the range of 0.85 to 1.50, and the opening of the fiber surface. The aperture ratio was in the range of 2 to 15%. Table 1 shows the results of various measurements.
[0124]
　[Comparative Example 1]
　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 80,000. Table 1 shows the results of various measurements.
[0125]
　[Comparative Example 2]
　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 165,000. Table 1 shows the results of various measurements.
[0126]
　[Comparative Example 3]
　The same as in Example 1 except that the number of fibers in the fiber bundle was changed to 45,000, the length of the accommodating portion of the tubular case was changed to 80 mm, and the inner diameter of the accommodating portion was changed to 30 mm. A purification column was prepared. Table 1 shows the results of various measurements.
[0127]
　[Comparative Example 4]
　Purification 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 accommodating portion of the tubular case was changed to 25 mm, and the inner diameter of the accommodating portion was changed to 70 mm. A column was made. Table 1 shows the results of various measurements.
[0128]
　[Comparative Example 5]
　A purification column was produced in the same manner as in Example 1 except that a fiber bundle wound without applying tension when winding with a skein was used. Table 1 shows the results of various measurements.
[0129]
　[Comparative Example 6]
　A purification column was produced in the same manner as in Example 1 except that the fiber bundle wound up without using the traverse mechanism was used when winding up with a skein. Table 1 shows the results of various measurements.
[0130]
　[Comparative Example 7]
　In the preparation of the fiber bundle, 16 parts by mass of polysulfone (Udelpolysulfone (registered trademark) P-3500 manufactured by Solvay) is mixed with 84 parts by mass of N, N-dimethylacetamide (DMAc) at 60 ° C. The undiluted spinning solution was prepared by stirring for 8 hours. The obtained undiluted spinning solution was discharged from a base having a cylindrical shape, and after running the drywall portion by 350 mm, it was guided to a coagulation bath and passed through the bath. As the atmosphere of the drywall, cold air having a temperature of 30 ° C. and a humidity of 80% was blown perpendicularly to the porous fibers. Water was used for the coagulation bath, and the water temperature (coagulation bath temperature) was 40.0 ° C. After washing each porous fiber with water, it was wound up at 30 m / min with a skein. Table 1 shows the results of various measurements.
[0131]
　[Comparative Example 8]
　A purification column was produced in the same manner as in Example 1 except that the temperature of the atmosphere of the drywall in spinning was 1 ° C. and the dew point of cold air was −20 ° C. Table 1 shows the results of various measurements.
[0132]
　[Comparative Example 9]
　A purification column was produced in the same manner as in Example 1 except that the temperature of the atmosphere of the drywall in spinning was 25 ° C. and the dew point of cold air was 20 ° C. Table 1 shows the results of various measurements.
[0133]
[Table 1]

[0134]
　Comparing Example 1 with Comparative Example 1, it can be seen that the adsorption performance of β2-microglobulin significantly decreases as the filling rate decreases. This is because the amount of fibers is small, the liquid to be treated flows between the fibers, and the liquid to be treated is difficult to sufficiently contact with the fibers. In the comparison between Example 1 and Comparative Example 2, it can be seen that the pressure loss increases and the hemolysis rate further increases as the filling rate increases. It is speculated that when the pressure loss is large, the shear stress applied to the blood cells increases, causing hemolysis.
[0135]
　In the comparison between Example 1 and Comparative Examples 3 and 4, it can be seen that the pressure loss increases when the inner diameter of the accommodating portion is small and the adsorption performance decreases when the inner diameter of the accommodating portion is large, while the fiber filling rate is set to the same level. .. This is because when the inner diameter of the accommodating portion is small, the flow rate per cross-sectional area increases, and when the inner diameter of the accommodating portion is large, the liquid to be treated does not flow to the outer peripheral portion, and fibers that do not contribute to the adsorption performance are generated. I'm guessing it's because.
[0136]
　In the comparison between Example 1 and Comparative Examples 5 and 6, when the manufacturing method such as winding conditions is changed, the fiber bundle meanders and the linearity decreases. It can be seen that when it is less than 0.97, the pressure loss increases and the hemolysis rate further increases. When the pressure loss is large, the shear stress applied to the blood cells increases. Furthermore, it is speculated that hemolysis was caused as a result of increased opportunities for contact, collision, and scraping of blood cells and fibers.
[0137]
　In the comparison between Example 1 and Comparative Example 7, it can be seen that when the value represented by wet Ra / dry Ra is out of the claims and less than 1.05, the amount of IgG adsorbed increases. It is speculated that this is because the polymer chains on the fiber surface are not sufficiently swollen.
[0138]
　In the 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 lowered. Furthermore, the adsorption performance of β2-microglobulin also deteriorates in the purification column produced using this fiber bundle. It is presumed that this is because when the fiber surface is smooth, the liquid to be treated near the surface becomes a straight line and a boundary layer is formed.
[0139]
　In the 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 can be seen that the purification column produced using this fiber bundle has an increased hemolysis rate. It is presumed that this is because the blood cells have increased the chances of contact, collision, and scraping with the unevenness of the fiber surface, and hemolysis has occurred.
Code description
[0140]
　1 Purification column
　2 Header
　3 Distribution plate
　4 Cylindrical case
　5 Adsorbent
　6 β2-MG clearance measurement circuit
　7 Pump
　8 Circulation bovine blood
　9 Clearance bovine blood
10 Hot water bath
11 Disposal beaker
The scope of the claims
[Request item 1]
A fiber bundle containing a plurality of porous fibers that satisfy 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 surface of the porous fiber. The arithmetic mean roughness (wet Ra value) in the 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) (fiber bundle length). ) / (Length of one porous fiber), the linearity of the fiber bundle is 0.97 or more and 1.00 or less.
[Request item 2]
　When the diameter of the inscribed circle is Di and the diameter of the circumscribed circle is Do in the cross section of the porous fiber, the degree of deformation of the cross section of the porous fiber represented by Do / Di is 1.3 or more. The fiber bundle according to claim 1, which is 5 or less.
[Request Item 3]
　The fiber bundle according to claim 1 or 2, wherein the average pore radius of the porous fiber is 0.8 nm or more and 90 nm or less.
[Request Item 4]
　The fiber bundle according to any one of claims 1 to 3, wherein the porous fiber has a homogeneous porous structure in the cross-sectional direction.
[Request Item 5]
　The fiber bundle according to any one of claims 1 to 4, wherein the surface opening ratio of the porous fiber is 0.1% or more and 30% or less.
[Request Item 6]
　The fiber bundle according to any one of claims 1 to 5, wherein the diameter corresponding to a circle in the cross section of the porous fiber is 10 μm or more and 1000 μm or less.
[Request Item 7]
The fiber bundle according to any one of claims 1 to 6, 　wherein the amount of IgG adsorbed on the porous fiber is 13 mg / cm 3 or less.
[Request Item 8]
The fiber bundle according to any one of claims 1 to 7, 　wherein the amount of the tumor necrosis factor α (TNFα) adsorbed on the porous fiber is 15 μg / cm 3 or more.
[Request Item 9]
　The fiber bundle according to any one of claims 1 to 8 is housed substantially parallel to the longitudinal direction of the tubular case, and an inlet port and an outlet port for the liquid to be treated are provided at both ends of the tubular case, respectively. Purification column with a header attached.
[Request Item 10]
　A fiber bundle formed by bundling two or more fibers is housed substantially parallel to the longitudinal direction of the tubular case, and a header having an inlet port and an outlet port for the liquid to be treated is provided at both ends of the tubular case, respectively. A purification column that is attached and meets the following requirements (i) to (v).
(I) Assuming that the diameter of the inscribed circle in the cross section of the fiber is Di and the diameter of the circumscribed circle is Do, the degree of deformation of the cross section of the fiber represented by Do / Di is 1.3 or more and 8.5. The following
(ii) the filling rate of the fiber in the accommodating portion is 40% or more and 73% or less
(iii) the inner diameter of the accommodating portion is 32 mm or more and 60 mm or less
(iv) (fiber bundle accommodated in the purification column). The linearity of the fibers represented by) / (the length of one fiber housed in the purification column) is 0.97 or more and 1.00 or less
(v) The flow of the liquid to be treated in the house. The capacity of the road is 5 mL or more and 60 mL or less.
[Request Item 11]
　The purification column according to claim 10, wherein the pressure loss when bovine blood is flowed at a flow rate of 200 mL / min for 1 hour is 1 kPa or more and 20 kPa or less.
[Request Item 12]
　The purification column according to claim 10 or 11, wherein the increase in hemolysis rate represented by the following formula is 1.0 or less when bovine blood is flowed at a flow rate of 400 mL / min for 4 hours.
　Increased hemolysis rate = hemolysis rate of bovine blood after circulation-hemolysis rate of bovine blood before circulation
[Request Item 13]
　The purification column according to any one of claims 10 to 12, wherein the β2-microglobulin (β2-MG) clearance when bovine blood is flowed at a flow rate of 200 mL / min for 1 hour is 35 mL / min or more and 120 mL / min or less. ..
[Request Item 14]
　A method for producing a fiber bundle, which focuses the fibers under the conditions satisfying the following (a) and (b).
(A) The tension at the time of winding the fiber around the skein is 0.5 gf / piece or more and 10.0 gf / piece or less
. Distance from parallel movement in the vertical direction) is 0.1 mm or more and 30 mm or less.
[Request Item 15]
　The method for producing a purification column according to claim 14, further focusing the fibers under the conditions satisfying the following (c) and (d).
(C) The average value of the traverse stroke (maximum distance that the traverse roller moves in the axial direction of the skein) at the time of winding the fiber to the skein is the middle stage in the early, middle and final stages of winding with traverse> It satisfies the relation of final stage = initial stage
(d) The number of changes of the traverse stroke is any one of 4, 6, 8, 10, and 12.