Porous fiber, fiber bundle, adsorption column, and method for producing pharmaceutical using same

Abstract

The purpose of the present invention is to provide a porous fiber, a fiber bundle, and an adsorption column incorporating the fiber bundle with which it is possible to efficiently adsorb primarily high molecular weight substances to be adsorbed and removed which are larger than albumin. The present invention provides a porous fiber containing an organic polymer. The average pore diameter in a cross section of the fiber is 100-1,000 nm. The average pore diameter in the fiber outer surface is 100-10,000 nm. When the average pore diameter in an intermediate region of the fiber cross-section is denoted as Rm and the average pore diameter near the center is denoted as Ri, Rm / Ri is 0.85-1.15. The porosity of the fiber outer surface is 5-50%.

Description

Porous fiber, fiber bundle, and adsorption column, and method for manufacturing pharmaceuticals using the same

[0001] The present invention relates to a porous fiber, a fiber bundle, an adsorption column, and a method for producing a pharmaceutical product using the same.

[0002] Many adsorbents incorporated into adsorption columns for adsorbing and removing target substances contained in a liquid to be treated are porous in order to increase the surface area that contributes to adsorption. Adsorbents are generally in the form of beads or fibers. Fiber-shaped adsorbents include hollow fibers, solid fibers, and knitted solid fibers. Among these, hollow fibers and solid fibers are advantageous in that they can provide a sufficient flow path for the liquid to be treated when incorporated into an adsorption column.

[0003] For example, Patent Document 1 discloses a porous hollow fiber separation membrane with controlled pore size for the purpose of separating high-molecular-weight proteins such as immune complexes from medium-molecular-weight proteins equal to or smaller than albumin, low-molecular-weight proteins, and water.

[0004] Patent Documents 2 and 3 disclose porous solid fibers that adsorb proteins with lower molecular weights than albumin.

[0005] Patent Document 4 lists crystalline polymers such as polyethylene and polypropylene, and amorphous polymers such as polysulfone, polystyrene, and polymethyl methacrylate, and discloses porous solid fibers having uniform pores near the outer surface and near the center of the fiber.

[0006] Patent Documents 5 and 6 disclose porous hollow fiber separation membranes made of polysulfone in which the pore size and porosity on the inner (outer) surface of the hollow fiber are controlled in order to obtain sufficient mechanical strength and filtration flow rate.

[0007] Japanese Patent Application Laid-Open No. 58-76104 Japanese Patent Application Laid-Open No. 2014-207989 International Publication No. 2017 / 188119 Japanese Patent Application Laid-Open No. 6-296860 Japanese Patent Application Laid-Open No. 7-258915 Japanese Patent Application Laid-Open No. 2004-098027

[0008] However, the hollow fiber separation membrane described in Patent Document 1 is different in that it utilizes its hollow shape to remove the target substances contained in the liquid to be treated by separation.

[0009] Furthermore, in order to efficiently adsorb and remove high-molecular-weight proteins, it is necessary to design the pore size inside the fiber to be large. However, generally, the larger the pore size, the lower the fiber density and the lower the mechanical strength, which tends to deteriorate the spinnability. However, Patent Document 1 does not disclose any solution to the problem of deterioration of spinnability.

[0010] The porous solid fibers described in Patent Documents 2 and 3 do not describe highly efficient adsorption and removal of high-molecular-weight proteins larger than albumin, a medium-molecular-weight protein, and therefore do not describe a solution to the problem of poor spinnability due to large pore sizes.

[0011] The porous solid fibers described in Patent Document 4 are exemplified by crystalline polymers and amorphous polymers, but there is no description of improving the deterioration of spinnability, which is a concern particularly in amorphous polymers whose fibers have weak mechanical strength.Furthermore, there is no description of controlling the porous structure of the fiber surface to improve the deterioration of spinnability.

[0012] The hollow fibers described in Patent Documents 5 and 6, like Patent Document 1, differ in that they utilize their hollow shape to remove substances to be removed from a liquid to be treated by separation. Furthermore, although there are descriptions regarding the pore size and porosity of the inner (outer) surface of the fiber, the pore size in the cross section of the fiber has a porous structure in which the pore size changes continuously from the outer surface to the inner surface, which cannot be said to be an optimal structure from the viewpoint of adsorbing the substances to be removed by the pores.

[0013] Therefore, an object of the present invention is to provide porous fibers, fiber bundles, and adsorption columns having fiber bundles that are capable of highly efficiently adsorbing substances to be adsorbed and removed, mainly high-molecular-weight proteins larger than albumin.

[0014] Another object of the present invention is to provide porous fibers, fiber bundles, and adsorption columns having fiber bundles that have high mechanical strength and excellent spinnability despite the large pore size of the fibers.

[0015] The present invention for solving the above problems is configured as any one of the following (1) to (13): (1) A porous fiber containing an organic polymer, having an average pore size in a fiber cross section of 100 to 1,000 nm, an average pore size on the fiber outer surface of 100 to 10,000 nm, where Rm is the average pore size in the intermediate region of the fiber cross section and Ri is the average pore size near the center, Rm / Ri = 0.85 to 1.15, and the porosity of the fiber outer surface is 5 to 50%. (2) The porous fiber according to (1), wherein the porosity of the fiber outer surface is 5 to 40%. (3) The porous fiber according to (1) or (2), wherein the aspect ratio of the major axis to the minor axis of the pores on the fiber outer surface is 1.5 to 10. (4) The dispersion component of the surface free energy is 5 to 100 mJ / m ２ (5) The porous fiber according to any one of (1) to (3), wherein the organic polymer is an amorphous polymer. (6) The porous fiber according to any one of (1) to (4), wherein the amorphous polymer is an acrylic polymer. (7) The porous fiber according to (5), wherein the amorphous polymer is polymethyl methacrylate. (8) The porous fiber according to any one of (1) to (7), wherein the cross section of the fiber has Region A and Region B separated by a region boundary, Region A has a uniform structure with an average pore size Ap of 100 nm to 1000 nm, and Region B has an average pore size Bp smaller than Ap or is non-porous. (9) The porous fiber according to any one of (1) to (8), wherein the porous fiber is a solid fiber. (10) A fiber bundle comprising the porous fiber according to any one of (1) to (9). (11) An adsorption column comprising the fiber bundle according to (10). (12) The adsorption column according to (11), which is used for blood purification. (13) A method for producing a pharmaceutical product, comprising a purification step, using the adsorption column according to (10) or (11).

[0016] The porous fiber of the present invention has excellent spinnability despite its large pore diameter, and a fiber bundle made of the porous fiber and an adsorption column having the fiber bundle can highly efficiently adsorb high molecular weight proteins and the like contained in the liquid to be treated.

[0017] 4A is a diagram showing an example of a scanning electron microscope image in which virtual region 1 and virtual region 2 are distinguished by brightness difference. It is an enlarged view of the virtual region boundary portion of FIG. 1. It is a schematic diagram showing a pore size line profile in a perpendicular line to a tangent line at an arbitrary point of the virtual region boundary of FIG. 2. It is an example of a change in cross-sectional pore size at the region boundary, and is a schematic diagram (FIG. 4-A) when the cross-sectional pore size changes discontinuously, a schematic diagram (FIG. 4-B) when the cross-sectional pore size changes continuously, and a schematic diagram (FIG. 4-C) when there are locally large and small cross-sectional pore size portions. It is an example of an X-ray scattering spectrum in which a peak derived from microcrystals overlaps with a peak derived from amorphous, forming a shoulder peak. It is an example of an ultra-small angle X-ray scattering spectrum of a spinning dope when X-ray scattering is measured.

[0018] The porous fiber, fiber bundle, and adsorption column of the present invention will be described in detail below.

[0019] The porous fiber of the present invention contains an organic polymer, and is characterized in that the average pore size on the outer surface of the fiber is 100 to 10,000 nm, the average pore size on the cross section of the fiber is 100 to 1,000 nm, and when the average pore size in the intermediate region of the cross section of the fiber is Rm and the average pore size near the center is Ri, Rm / Ri=0.85 to 1.15, and the porosity of the outer surface of the fiber is 5% to 50%.

[0020] The term "fiber cross section" refers to a plane perpendicular to the longitudinal direction of the porous fiber of the present invention.

[0021] The "fiber outer surface" refers to the outer peripheral surface of the porous fiber of the present invention, that is, the outer peripheral portion of the fiber cross section.

[0022] Porous Fiber The fiber shape of the porous fiber of the present invention may be either a hollow fiber having a hollow portion or a solid fiber having no hollow portion. However, a solid fiber is preferred because it has a high fiber volume per unit volume, resulting in excellent adsorption performance, high mechanical strength, and excellent spinnability.

[0023] In the porous fiber of the present invention, the "average pore size on the outer surface of the fiber" and the "average pore size on the cross section of the fiber" may be appropriately controlled depending on the size of the substance to be adsorbed and removed. However, from the viewpoint of preventing clogging of the pores and utilizing the interior of the porous fiber to achieve highly efficient adsorption, the following two designs are preferred.

[0024] That is, it is preferable to design each average pore size to be larger than the size of the substance to be adsorbed and removed. Also, it is preferable to design the average pore size on the outer surface of the fiber to be larger than the average pore size in the cross section of the fiber. These average pore sizes can be controlled by the type and concentration of the spinning dope, the temperature and humidity of the dry section during spinning, the temperature of the coagulation bath, etc., as described below.

[0025] Substances to be adsorbed and removed by the porous fiber of the present invention include, for example, LDL cholesterol, immune complexes, endotoxins, and proteoglycans, which will be described later, and have a weight-average molecular weight of several hundred thousand to several million and a size of about 15 nm to 100 nm.

[0026] From the viewpoint of highly efficient adsorption of the target substances for adsorption and removal, the average pore diameter of the outer surface of the fiber is preferably 100 nm or more, more preferably 200 nm or more, and even more preferably 300 nm or more. On the other hand, from the viewpoint of maintaining the mechanical strength of the fiber, the average pore diameter of the outer surface of the fiber is preferably 10,000 nm or less, more preferably 5,000 nm or less, and even more preferably 1,000 nm or less. Here, if the pores on the outer surface of the fiber are not circular, the average pore diameter of the outer surface of the fiber can be calculated using the equivalent diameter obtained from a circle having the same area as the area enclosed by the outer periphery of the pore.

[0027] Fiber Cross Section Furthermore, from the viewpoint of highly efficient adsorption of the target substances for adsorption and removal, the average pore diameter of the fiber cross section is preferably 100 nm or more, more preferably 125 nm or more, and even more preferably 150 nm or more. On the other hand, from the viewpoint of maintaining the mechanical strength of the fiber, the average pore diameter of the fiber cross section is preferably 1000 nm or less, more preferably 750 nm or less, and even more preferably 500 nm or less. Here, if the pores in the fiber cross section are not circular, the average pore diameter of the fiber cross section can be calculated using the equivalent diameter obtained from a circle having the same area as the area enclosed by the outer periphery of the pore.

[0028] It has been found that, in the present invention, the "average pore size in the fiber cross section" is such that the average pore size Rm in the intermediate region located halfway between the outer surface and the center is approximately the same as the average pore size Ri near the center, which is important for highly efficient adsorption of the substances to be adsorbed and removed.

[0029] In separation membranes that use the principle of filtration, porous fibers in which the pore size in the fiber cross section changes continuously from the outer surface to the interior of the fiber are preferably used to prevent clogging, as described in Patent Document 6. However, when target substances are removed by adsorption, it is preferable that the pore sizes suitable for adsorbing the target substances to be adsorbed and removed are uniformly distributed from the middle region of the fiber to near the center, as this enables highly efficient adsorption. Specifically, the ratio Rm / Ri is preferably 0.85 to 1.15, and more preferably 0.90 to 1.10.

[0030] On the other hand, in the present invention, the "average pore size in the fiber cross section" is preferably set so that the average pore size near the outer surface is larger than the average pore size near the center, thereby providing a porous fiber that can efficiently adsorb substances to be adsorbed and removed, has high mechanical strength, and is excellent in spinnability.

[0031] Specifically, when the average pore size near the outer surface is Ro and the average pore size near the center is Ri, from the viewpoint of ensuring spinnability, the value of Ro / Ri is preferably 1.3 or more, more preferably 1.4 or more, and even more preferably 1.5 or more. On the other hand, from the viewpoint of highly efficient adsorption, the value of Ro / Ri is preferably 4.0 or less, more preferably 3.5 or less, and even more preferably 3.0 or less.

[0032] From the viewpoint of highly efficient adsorption of the target substances for adsorption and removal, Ro is preferably 150 nm or more, more preferably 180 nm or more, and even more preferably 200 nm or more. On the other hand, from the viewpoint of maintaining the mechanical strength of the fiber, Ro is preferably 1000 nm or less, more preferably 800 nm or less, and even more preferably 700 nm or less. Here, when the pores in the cross section of the fiber are not circular, the average pore size in the cross section of the fiber can be calculated using the equivalent diameter determined from a circle having the same area as the area enclosed by the outer periphery of the pore.

[0033] Furthermore, from the viewpoint of highly efficient adsorption of the target substances for adsorption and removal, Ri is preferably 100 nm or more, more preferably 120 nm or more, and even more preferably 140 nm or more. On the other hand, from the viewpoint of maintaining the mechanical strength of the fiber, Ri is preferably 1000 nm or less, more preferably 750 nm or less, and even more preferably 500 nm or less. Here, when the pores in the fiber cross section are not circular, the average pore size in the fiber cross section can be calculated using the equivalent diameter determined from a circle having the same area as the area enclosed by the outer periphery of the pore.

[0034] In porous fibers, the "near the outer surface" refers to the region close to the outer periphery of the porous fiber, and refers to the region corresponding to 10% of the outer periphery when an arbitrary straight line is drawn from the center point of the fiber cross section to the periphery. Here, the center point refers to the center of gravity of the fiber cross section. The average pore size near the outer surface is the pore size of the region through which substances to be adsorbed and removed contained in the treated liquid penetrate from the outer surface of the fiber into the pores, and is therefore an important factor that greatly affects the adsorption efficiency of the substances to be adsorbed and removed.

[0035] However, in the vicinity of the outer surface of the porous fiber of the present invention, a small area of ​​dense layer present on the outermost surface is excluded. The "dense layer" refers to a region in the cross section of the fiber where there are no pores with a pore diameter of 15 nm or more.

[0036] In a porous fiber, the "near-center" refers to a region close to the center of the porous fiber, which corresponds to 10% of the center when a straight line is drawn from the center point to the periphery in the cross section of the fiber. Because the near-center region corresponds to the core of the porous fiber, the average pore size near the center is an important factor that greatly affects the mechanical strength.

[0037] The term "intermediate region" refers to a region located midway between the center and the outer surface of a porous fiber. Specifically, when a straight line is drawn from the center point of the fiber cross section to the outer periphery and the fiber cross section is divided into 10 small regions by dividing the line into 10 equal parts, the "intermediate region" refers to the fifth small region closest to the center point.

[0038] The cross-sectional shape of the porous fiber is not particularly limited, and may be circular or may be an irregular shape other than circular. Even in the case of an irregular shape, the "near the outer surface" is defined as a region corresponding to 10% of the outer periphery when an arbitrary straight line is drawn from the center point of the fiber cross-section to the periphery, the "near the center" is defined as a region corresponding to 10% of the inner periphery when an arbitrary straight line is drawn from the center point of the fiber cross-section to the periphery, and the "middle region" is defined as the fifth small region closest to the center when an arbitrary straight line is drawn from the center point of the fiber cross-section to the periphery and the fiber cross-section is divided into 10 small regions by dividing the line into 10 equal parts. The cross-sectional shape of the fiber can be controlled by the shape of the spinneret from which the spinning dope is discharged.

[0039] When the porous fiber is a hollow fiber, the terms "near the outer surface," "near the center," and "intermediate region" are defined excluding the hollow portion. That is, "near the outer surface" refers to 10% of the fiber cross section on the outer periphery, excluding the hollow portion, when a straight line is drawn from the center of the fiber cross section to the periphery, and "near the center" refers to 10% of the fiber cross section on the inner periphery, excluding the hollow portion. Furthermore, when a straight line is drawn from the center of the fiber cross section to the periphery, the line is divided into 10 equal parts, excluding the hollow portion, to divide the fiber cross section into 10 small regions, and the "intermediate region" refers to the fifth small region closest to the center.

[0040] These average pore sizes can be calculated by image analysis of images of the outer surface of the fiber or the cross section of the fiber observed with a scanning electron microscope or the like, as described in the Examples below.

[0041] The porous fiber of the present invention may contain a third component such as fine particles as a pore-forming agent or adsorbent inside the fiber. However, it is preferable that the porous fiber does not contain the third component, since this may result in a decrease in the mechanical strength of the porous fiber, a decrease in the efficiency of cleaning during spinning, or the third component may leach out from the inside of the porous fiber to the outside.

[0042] In one preferred embodiment, the porous fiber of the present invention has a region A having a uniform structure of 100 nm to 1000 nm and a region B separated by a region boundary, and the average pore size Bp of region B is smaller than the average pore size Ap of region A, or the porous fiber is non-porous. By forming a composite porous fiber having two regions with different pore sizes, it is possible to obtain a fiber with higher mechanical strength than a porous fiber having only region A.

[0043] Here, a method for determining area A, area B, and area boundaries will be described.

[0044] First, at a magnification that allows the entire fiber cross section to be observed, the approximate position of the region boundary between region A and region B is determined. This is called a virtual region boundary 102, and the regions separated by the virtual region boundary are called virtual region 1 (100) and virtual region 2 (101).

[0045] Next, the imaginary region boundaries are enlarged and observed at a magnification that allows the porous structure to be observed, and the exact positions of the boundaries between boundary 1 and region boundary and region boundary / boundary 2 are determined. Then, the cross-sectional pore diameters of region 1 and region 2 are determined, and the one with the larger cross-sectional pore diameter is determined to be region A, and the one with the smaller cross-sectional pore diameter is determined to be region B.

[0046] A specific description will be given below using Figures 1 to 3 as examples. The fiber cross section of a porous fiber is observed using a scanning electron microscope (e.g., S-5500, manufactured by Hitachi High-Technologies Corporation) at a magnification that allows the entire fiber cross section to be observed. In the porous fiber of the present invention, region A preferably has a uniform structure, and region A can be observed with uniform brightness. Furthermore, region B preferably has a smaller cross-sectional pore diameter than region A, and therefore virtual region 1 (100) and virtual region 2 (101) can be distinguished from each other by a virtual region boundary 102 based on brightness differences, as shown in Figure 1. If region A and region B are made of the same material, the difference in cross-sectional pore diameter is small (e.g., approximately 10 nm), and the brightness difference between the regions is small, the contrast and brightness are appropriately adjusted to increase the brightness difference between the regions. The virtual region boundary of the distinguished regions is determined by visual inspection or image processing. When visual inspection is performed, the location where the brightness changes visually is considered to be the virtual region boundary. When processing the image, the two regions are binarized so that the brighter region is white and the darker region is black, and the boundary between them is used as the virtual region boundary. At this time, the judgment is made ignoring unevenness that occurred when preparing the cross section of the porous fiber, brightness and darkness due to scratches, or brightness and darkness due to noise. When processing the image, appropriate image processing such as smoothing or noise removal is performed depending on the situation before binarization.

[0047] After determining the virtual region boundary, the image is enlarged to a magnification at which the pore structure can be observed, and the location where the pore structure changes is determined to be the accurate region boundary. The location where the pore structure changes is determined using the following image processing method. As shown in Figure 2, the pore diameters of pores present on the line profile of a perpendicular line 103 to a tangent at any point on the virtual region boundary 102 are plotted as shown in Figure 3. Here, using image analysis software (e.g., ImageJ), the pores are fitted to a circle, and the diameter of the circle obtained is taken as the pore diameter, and the center of the circle is taken as the position of the pore. As shown in Figure 3, the pore diameter within each region takes a constant value within a range of variation, but changes at a certain position. On the virtual region 1 side, the location where this pore diameter profile changes is taken as the accurate boundary position, i.e., the region 1 boundary 104, and on the virtual region 2 side, the location where a similar change occurs is taken as the region 2 boundary 105, and the region between the region 1 boundary 104 and the region 2 boundary 105 is taken as the region boundary 106.

[0048] The "region boundary" refers to the region separating Region 1 and Region 2. The region boundary may have a discontinuous change in cross-sectional pore size (Fig. 4-A) or a continuous change (Fig. 4-B). Also, there may be localized areas with larger or smaller cross-sectional pore sizes (Fig. 4-C).

[0049] For each region determined by the above method, the region having a larger cross-sectional pore diameter determined by the method described below in "Average pore diameter in fiber cross section" is designated as Region A, and the region having a smaller cross-sectional pore diameter is designated as Region B. Region A and / or Region B may exist in multiple locations on the fiber cross section, and in that case, similar measurements are made for each location.

[0050] The adsorption principle of the target substance to be adsorbed and removed by the porous fiber of the present invention may be any of hydrophobic interaction, electrostatic interaction, hydrogen bonding, etc., or a combination of these principles. Hydrophobic interaction is particularly preferred because it has sufficient force for adsorbing proteins and has little effect on blood cells, etc. These adsorption principles are basically determined by the material of the porous fiber, which will be described later.

[0051] It is also possible to immobilize multiple ligands that specifically interact with the substance to be adsorbed and removed on the outer surface of the porous fiber and within the pores of the porous fiber. However, it is preferable to immobilize only one or two types of ligands on the porous fiber, because it is difficult to simultaneously immobilize multiple ligands on the porous fiber, and even if immobilization is successful, competition between the ligands may reduce the amount of ligand immobilized and the adsorption performance.

[0052] The materials of the outer surface-nearby region and the center-nearby region of the porous fiber of the present invention may be the same or different, but it is preferable that the materials of each region are the same from the viewpoint of preventing peeling and deformation of the porous fiber due to differences in physical or chemical properties caused by the difference in materials.

[0053] From the viewpoint of achieving both blood compatibility and adsorption performance, the porous fiber of the present invention desirably has an appropriate degree of hydrophobicity on the outer surface of the fiber and on the surfaces of the pores inside the fiber. The hydrophobicity can be quantified by the dispersive component of the surface free energy, and specifically, the dispersive component of the surface free energy measured by inverse gas chromatography is 5 to 100 mJ / m２ It is preferable that the concentration is 10 to 80 mJ / m ２ , more preferably 20 to 70 mJ / m ２ As the material for the porous fiber of the present invention, an organic polymer is preferably used from the viewpoints of moldability, cost, etc. Examples of organic polymers include polymethyl methacrylate (hereinafter referred to as "PMMA"), polyacrylonitrile (hereinafter referred to as "PAN"), polyacrylamide, polysulfone, polyethersulfone, polyarylethersulfone, polypropylene, polystyrene, polycarbonate, polylactic acid, polyethylene terephthalate, cellulose, cellulose triacetate, ethylene-vinyl alcohol copolymer, polycaprolactam, polymethylpentene, polyvinylidene fluoride, polyester-based polymer alloys, and derivatives thereof. Among these, PMMA, PAN, polysulfone, polyethersulfone, polyester-based polymer alloys, polystyrene, and cellulose triacetate, which have an appropriate hydrophobic interaction, are preferably used, and PMMA is particularly preferably used.

[0054] Amorphous Polymer The porous fiber of the present invention preferably contains an amorphous polymer, and more preferably contains an amorphous polymer as the main component. Here, "amorphous polymer" refers to a polymer that solidifies when the temperature is lowered from a molten state to solidify, with the molecules remaining irregularly entangled. Here, "containing an amorphous polymer as the main component" means that, of the components constituting the porous fiber, amorphous polymer accounts for 50% by weight or more of the total. Amorphous polymers are particularly excellent in terms of moldability and cost, and have a uniform structure even from a microscopic perspective, which is expected to result in a uniform adsorption reaction on the surface.

[0055] In terms of the physical or chemical properties of the porous fiber, amorphous polymers are easy to handle as materials. Among amorphous polymers, PMMA is particularly preferred because it has moderate hydrophobicity, excellent mechanical strength, and can withstand radiation sterilization when used in medical applications.

[0056] When the porous fiber of the present invention contains an amorphous polymer, the presence of amorphous polymer-derived microcrystals in the porous fiber is preferred in order to obtain a porous fiber with high mechanical strength and excellent spinnability even when the average pore size on the outer surface or cross section of the fiber is controlled to be large. Generally, amorphous polymers are difficult to crystallize, but they can be partially crystallized by physical techniques such as stretching or pressurization, techniques using specific solvents, or techniques for controlling the stereoregularity of the polymer. For example, when a polymer has different optical isomers and they form a complex (hereinafter referred to as a "stereocomplex"), microcrystals may be formed.

[0057] The microcrystals derived from the amorphous polymer in the present invention can be confirmed by analyzing the crystal structure of the porous fiber, as described in the Examples below.

[0058] X-ray scattering measurement is used as a technique for analyzing the crystal structure. Wide-angle X-ray scattering (hereinafter referred to as "WAXS") using a high-intensity synchrotron radiation facility (e.g., SPring-8) is particularly preferred because of its high sensitivity compared to laboratory-level X-ray diffractometers (e.g., Rigaku's SmartLab).

[0059] As a means for determining whether microcrystals are present in the porous fiber, if the microcrystals are known, they can be determined to be present if a peak is observed at the peak position derived from the microcrystals by comparing the X-ray scattering data of the microcrystals with literature that describes the data. If the microcrystals are unknown, it can be determined whether the peak is derived from the microcrystals by performing X-ray structural analysis on the diffraction image obtained by WAXS.

[0060] In order to achieve excellent spinnability despite the large pore size and highly efficient adsorption of high-molecular-weight proteins and the like contained in the liquid to be treated, the porous fiber of the present invention preferably has an inter-crystalline lattice distance (d) of the microcrystals within an optimum range. The scattering vector q and the inter-crystalline lattice distance d have the relationship q = 2π / d.

[0061] To achieve high mechanical strength, the peak of the scattering vector (q) derived from the microcrystals of the amorphous polymer obtained by WAXS X-ray structural analysis is 1.2 Å. －１It is preferable that the distance between the crystal lattices of the amorphous polymer microcrystals is less than 0.05 mm. This means that the intercrystalline distance d of the crystal lattice of the amorphous polymer microcrystals is relatively large compared to the folded crystal structure generally seen in crystalline polymers. In other words, since the polymer has a more complex entangled crystalline structure, it is difficult to form crystals. However, once microcrystals are formed by a method using hydrogen bonding, which will be described later, a stable crystalline structure is formed in which the entanglement of the amorphous polymer molecules is difficult to unravel, and a porous fiber with high mechanical strength can be obtained.

[0062] On the other hand, if the crystal lattice distance is too large, it becomes difficult to form microcrystals. Therefore, in the porous fiber of the present invention, the peak of the scattering vector (q) derived from the microcrystals of the amorphous polymer obtained by X-ray structural analysis by WAXS is 0.2 Å. －１ It is preferable that the amount of HCl is more than 1000 ppm.

[0063] In particular, microcrystals are easily formed and high mechanical strength is obtained, so the peaks derived from the microcrystals of amorphous polymers obtained by WAXS X-ray structural analysis are 0.29, 0.84, and 1.14 Å. －１ It is preferable that a peak is observed in either of the above.

[0064] The amorphous polymer contained in the porous fiber of the present invention is preferably an acrylic polymer. In particular, acrylic polymers such as PMMA, PAN, or polyacrylamide are more preferred because they have excellent blood compatibility and can easily exhibit functions by modifying their end groups. Among them, PMMA is more preferred because, despite being an amorphous polymer, it has different optical isomers, namely, syndiotactic and isotactic isomers, which form a stereocomplex.

[0065] The porosity of the outer surface of the porous fiber of the present invention is preferably 5% or more, more preferably 10% or more, and even more preferably 15% or more, from the viewpoint of highly efficient adsorption of the target substances for adsorption and removal. On the other hand, the porosity of the outer surface of the porous fiber is preferably 50% or less, more preferably 40% or less, and even more preferably 35% or less, because this is expected to have the effect of preventing a decrease in the mechanical strength of the fiber, preventing non-selective adsorption, and preventing fine particles generated inside the pores from escaping to the outside of the fiber.

[0066] Furthermore, the aspect ratio of the major axis (the longest radius of the pore) to the minor axis (the shortest radius of the pore) is important for the pores on the outer surface of the fiber in the present invention. When the major axis is Rl and the minor axis is Rs, the value of Rl / Rs is preferably 1.5 or more, more preferably 2.5 or more, and even more preferably 4.0 or more, in order to efficiently adsorb and remove the target substances for adsorption and removal. On the other hand, from the viewpoint of maintaining the mechanical strength of the fiber, the value of Rl / Rs is preferably 10 or less, more preferably 8 or less, and even more preferably 7 or less.

[0067] The porosity and aspect ratio of the outer surface of the fiber can be calculated by image analysis of an image of the outer surface of the fiber observed with a scanning electron microscope or the like, as described in the Examples below.

[0068] The porous fiber of the present invention may be produced by any of melt spinning, solution spinning, and the like. It is also possible to make the composite fiber obtained by melt spinning porous by post-treatment such as drawing or extraction. However, when the composite fiber is made porous by drawing, the Rl / Rs value of the outer surface of the fiber becomes very large, making it difficult to maintain mechanical strength. Furthermore, when the composite fiber is made porous by extraction, the process tends to be complicated.

[0069] On the other hand, in solution spinning, fibers with the desired porous structure can be obtained by uniformly dissolving the fiber material in a solvent and then removing the solvent. Furthermore, since post-processing to make the fibers porous, as in melt spinning, is not required, productivity is excellent and there is little risk of peeling or breakage. For these reasons, solution spinning is preferred as the method for producing the porous fiber of the present invention.

[0070] In addition, in order to control the surface structure and pore size of porous fibers, a method utilizing phase separation between the organic polymer and the solvent in the spinning dope during solution spinning is preferably used. Techniques utilizing phase separation include thermally induced phase separation and non-solvent induced phase separation, and which method is more suitable depends on the material of the organic polymer and the desired pore size range.

[0071] However, in the present invention, it is preferable to use a thermally induced phase separation method that can be controlled between the stock solution production step, the discharge step, and the cooling step described below, and it is even more preferable to combine a thermally induced phase separation method with a non-solvent induced phase separation method that can be controlled not only in the stock solution production step, the discharge step, and the cooling step, but also in the solidification step described below.

[0072] Hereinafter, methods for producing porous fibers obtained by solution spinning will be described, but the method is not limited to these.

[0073] The porous fiber of the present invention comprises a "stock solution production step of dissolving an organic polymer in a solvent to obtain a spinning dope", followed by a "discharge step of heating the spinning dope to a gel point or higher and discharging it from a spinneret", followed by a "cooling step of cooling the spinning dope to a gel point or lower in a dry section after discharging it from the spinneret", and a "coagulation step of forming a porous fiber in a coagulation bath containing a compound that is incompatible with the organic polymer in the spinning dope", and the spinning dope has a scattering vector (q) of 1 nm in ultra-small angle X-ray scattering measurement at a temperature higher than the gel point. －１ The following scattering can be obtained by the manufacturing method.

[0074] The "process for producing a spinning dope by dissolving an organic polymer in a solvent" refers to a process for obtaining a spinning dope by dissolving a solid organic polymer in a solvent. The dissolving method is not particularly limited, but a method in which the organic polymer and the solvent are placed in a container and heated and stirred until a homogeneous solution is obtained is preferably used. The form of the solid is not particularly limited, but a powder or flake form is preferred to enhance solubility. The spinning dope of the present invention has a gel point from the viewpoint of improving spinnability and controlling pore size.

[0075] The "discharge step of heating the spinning dope to above its gel point and discharging it from the spinneret" refers to a step of heating the spinning dope obtained in the above-mentioned dope production step to above its gel point and discharging it from the spinneret. Heating it to above its gel point increases the fluidity of the spinning dope, resulting in good dischargeability from the spinneret. Here, the gel point refers to the temperature at which the spinning dope, which is in a fluid liquid state at high temperatures, transitions to a non-fluid gel state when cooled. Methods for determining the gel point include visual observation and viscosity measurement, but viscosity measurement is used in the present invention. In the case of viscosity measurement, the temperature at which the viscosity increases rapidly can be determined as the gel point. Methods for measuring viscosity include a rheometer and a falling ball method.

[0076] The "cooling step of cooling the spinning dope to below the gel point in the dry section after being discharged from the spinneret" refers to a step of cooling the spinning dope discharged from the spinneret to below the gel point. This increases the mechanical strength of the porous fiber obtained through the coagulation step described below, improving spinnability, and also enabling control of the pore size by thermally induced phase separation.

[0077] The "coagulation step of forming porous fibers in a coagulation bath containing a compound that is incompatible with the organic polymer in the spinning dope" refers to a step in which the spinning dope (a precursor of the porous fiber containing a solvent) that has been subjected to the above-mentioned discharge step and cooling step is introduced into a coagulation bath, and a material exchange occurs between the solvent used in the dope production step and the compound that is incompatible with the organic polymer contained in the coagulation bath, resulting in the precipitation of the organic polymer, thereby forming porous fibers.

[0078] In the present invention, the porous structure of the fiber cross section and outer surface of the obtained porous fiber can be influenced by controlling the nanodomain structure in the spinning dope, which is derived from phase separation and gelation.

[0079] In the present invention, the spinning dope has a scattering vector (q) of 1 nm in ultra-small angle X-ray scattering measurement at a temperature higher than its gel point. －１ It is preferable to have a scattering vector (q) of 1 nm in ultra-small angle X-ray scattering measurements. －１The presence of scattering below means that a nano-domain structure of several nanometers or more is formed in the spinning dope. That is, the nano-domain structure is already formed in the spinning dope during the extrusion process from the spinneret heated to the gel point or higher, and the nano-domain structure grows and is fixed through the cooling and solidification processes, thereby determining the pore structure of the porous fiber.

[0080] Here, "growth of nano-domain structure" means that the difference in concentration between the polymer-dilute phase and the polymer-rich phase that form the nano-domain structure increases, or that the size of the nano-domain structure increases. Fixation of the nano-domain structure means that the growth of the nano-domain structure stops and settles into a certain state due to the exchange of the solvent in the spinning dope with the solvent in the coagulation bath in the coagulation process. On the other hand, if the nano-domain structure does not exist at temperatures higher than the gel point, the formation of the nano-domain structure begins after the material is cooled to below the gel point in the cooling process. In the spinning dope, the mobility of the organic polymer is relatively reduced below the gel point, so the growth of the nano-domain structure is suppressed, resulting in a fiber with a smaller pore size than the porous fiber of the present invention.

[0081] Using this spinning solution, the "discharge step of heating the spinning solution to above the gel point and discharging it from the spinneret" described below and the "cooling step of cooling the spinning solution to below the gel point in the dry section after being discharged from the spinneret" described below are carried out, whereby a nanodomain structure is grown and fixed, and pores for adsorbing high-molecular-weight proteins with high efficiency are formed.

[0082] The spinning dope of the present invention may be composed only of an organic polymer and a good solvent, but preferably contains a poor solvent for the organic polymer in addition to the organic polymer and the good solvent. Here, a good solvent is a solvent that can dissolve the organic polymer, and a poor solvent is a solvent that does not dissolve the organic polymer even when heated to a high temperature. This is because, rather than achieving a homogeneous state in which the organic polymer and the good solvent are completely compatible with each other, the addition of a poor solvent adjusts the affinity of the organic polymer for the solvent and controls phase separation, i.e., controls the formation of a nanodomain structure.

[0083] As the organic polymer material used in the raw material production step, the organic polymers exemplified above as the material for the porous fiber are suitably used.

[0084] The solvent used in the raw solution production step includes a good solvent for the organic polymer. Although a single type of good solvent or a mixture of multiple types can be used, it is preferable to use only a single type from the viewpoints of cost and resource recovery.

[0085] Specific good solvents, when the organic polymer is PMMA, include, for example, aromatic compounds such as benzene, toluene, and xylene, ketone compounds such as acetone, alcohol compounds such as methanol, ethanol, iso-propanol, and benzyl alcohol, ester compounds such as ethyl acetate and butyl acetate, halogen-containing compounds such as chloroform, dichloromethane, and chlorobenzene, as well as tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, dimethylacetamide, N-methylpyrrolidone, and acetonitrile. Among these, dimethyl sulfoxide (hereinafter referred to as "DMSO") is preferably used because of its generally high solubility and high boiling point.

[0086] The type of poor solvent is not particularly limited, but when the organic polymer is PMMA, preferred examples include water, methanol, ethanol, n-propanol, iso-propanol, 1-butanol, ethylene glycol, propylene glycol, diethylene glycol, 1,3-propanediol, 1,4-butanediol, alcohol compounds such as glycerin and phenols, ether compounds such as diethyl ether, 1,4-dioxane and diglyme, hydrocarbon compounds such as hexane and heptane, amino group-containing compounds such as ethanolamine and formamide, acetic acid, formic acid, mercaptoethanol, and carbon disulfide.

[0087] Furthermore, in the relationship between the organic polymer and the poor solvent, it is important that there is an interaction such as a hydrophobic interaction, an electrostatic interaction, or a hydrogen bond for the purpose of controlling the nano-domain structure, promoting the formation of microcrystals of the organic polymer, and improving spinnability. Although a combination of these principles may be used, a hydrogen bond is more preferable because the strength of the interaction is appropriate.

[0088] Specifically, it is preferable that the organic polymer is a polymer containing a hydrogen bond donor functional group and the poor solvent is a hydrogen bond acceptor compound, or that the organic polymer is a polymer containing a hydrogen bond acceptor functional group and the poor solvent is a hydrogen bond donor compound. By forming hydrogen bonds between the organic polymer and the poor solvent, the orientation of the hydrogen bond-forming functional groups, hydrogen bond donor or acceptor functional groups present in the organic polymer is controlled, thereby controlling the higher-order structure of the organic polymer. This is thought to promote the formation of microcrystals in the organic polymer, thereby increasing the mechanical strength of the porous fiber and improving spinnability. Furthermore, the formation of an interaction with the poor solvent makes it possible to appropriately control the mobility of the organic polymer, thereby controlling the formation of a nanodomain structure.

[0089] From these points of view, the poor solvent is preferably a compound containing a hydrogen bond donor or acceptor functional group.

[0090] The specific compound containing a hydrogen bond donor functional group is not particularly limited, but is preferably water or a compound having a hydroxyl group or an amino group, and more preferably, for example, water, ethylene glycol, propylene glycol, 1,4-butanediol, glycerin, or formamide.

[0091] Specific examples of compounds containing a hydrogen bond acceptor functional group include ketone compounds and ester compounds, and acetone, ethyl acetate, and butyl acetate are preferred. The poor solvent may be a combination of any of these compounds containing a hydrogen bond donor functional group and compounds containing a hydrogen bond acceptor functional group.

[0092] The weight ratio of the poor solvent is not particularly limited, but an appropriate weight ratio can sufficiently promote the formation of the nano-domain structure and improve spinnability. The appropriate weight ratio of the poor solvent varies depending on the types of organic polymer, good solvent, and poor solvent, as the interaction and motility vary. For example, when PMMA is used as the organic polymer, DMSO as the good solvent, and water, an alcohol compound, or an amino group-containing compound as the poor solvent, the weight ratio of the poor solvent to the total solvent is preferably 1 wt% or more, more preferably 3 wt% or more, and even more preferably 5 wt% or more. On the other hand, the weight ratio of the poor solvent to the total solvent is preferably 25 wt% or less, more preferably 15 wt% or less, and even more preferably 10 wt% or less.

[0093] The weight ratio of the organic polymer to the entire spinning dope used in the dope production step is not particularly limited, but from the viewpoint of maintaining the mechanical strength of the porous fiber obtained by promoting physical and chemical crosslinking, such as entanglement and gelation of the organic polymers, the weight ratio of the organic polymer to the entire spinning dope is preferably 5% by weight or more, more preferably 7.5% by weight or more, and even more preferably 10% by weight or more. On the other hand, from the viewpoint of improving the dischargeability of the spinning dope and increasing the number of pores in the obtained porous fiber, the weight ratio of the organic polymer to the entire spinning dope is preferably 20% by weight or less, more preferably 18% by weight or less, and even more preferably 15% by weight or less.

[0094] Furthermore, from the viewpoint of maintaining the mechanical strength of the resulting porous fiber by promoting physical and chemical crosslinking, such as entanglement and gelation of organic polymers, the weight-average molecular weight of the organic polymer in the spinning dope used in the dope production step is preferably 10,000 or more, more preferably 50,000 or more, and even more preferably 100,000 or more.

[0095] On the other hand, since the spinning dope becomes highly viscous and therefore difficult to extrude from a spinneret in the extrusion step, the weight-average molecular weight of the organic polymer in the spinning dope used in the dope production step is preferably 10 million or less, more preferably 5 million or less, and even more preferably 3 million or less.

[0096] The temperature in the discharge step is not particularly limited, but from the viewpoint of stably maintaining the nano-domain structure obtained in the dope production step and from the viewpoint of maintaining the concentration of the spinning dope appropriately and stably discharging it from the spinneret, the temperature in the discharge step is preferably heated to a temperature equal to or higher than the gel point of the spinning dope. For example, in the case of a spinning dope containing PMMA and DMSO, the temperature in the discharge step is preferably 70°C or higher, more preferably 80°C or higher, and even more preferably 85°C or higher. On the other hand, in order to avoid decomposition of the components of the spinning dope, the temperature in the discharge step is preferably 150°C or lower, more preferably 130°C or lower, and even more preferably 110°C or lower.

[0097] In the cooling step, it is important that the spinning dope discharged from the spinneret is cooled to below the gel point in order to obtain a porous fiber having a large pore size and excellent mechanical strength. Although the temperature drop rate and cooling time are not particularly limited, natural cooling alone takes a long time to cool the dope to below the gel point, necessitating a slow spinning speed. Therefore, active cooling by blowing cold air, for example, is preferred. In the cooling step, the spinning dope discharged from the spinneret is cooled from the outer fiber surface, and therefore it is particularly important to control the pore size of the outer fiber surface of the porous fiber, the porosity of the outer fiber surface, and the cross-sectional pore size near the outer surface. When blowing cold air, the amount of cold air can be determined as long as it is sufficient to cool the dope to below the gel point and the risk of yarn breakage is reduced.

[0098] In the coagulation step, the spinning dope (a precursor of the porous fiber containing a solvent) that has been cooled undergoes solvent exchange with a compound that is incompatible with the organic polymer contained in the coagulation bath, resulting in precipitation of the organic polymer, thereby obtaining a porous fiber. The compound that is incompatible with the organic polymer is not particularly limited, but examples thereof include water and alcohol compounds.

[0099] The temperature of the coagulation bath is not particularly limited, but in order to stably maintain the porous structure, the temperature of the coagulation bath is preferably 100° C. or lower, more preferably 90° C. or lower, and even more preferably 80° C. or lower. On the other hand, in order to promote solvent exchange, the temperature of the coagulation bath is preferably 10° C. or higher, more preferably 20° C. or higher, and even more preferably 30° C. or higher.

[0100] In addition to the above steps, the method for producing the porous fiber of the present invention may also include a washing step, a heat treatment step, a stretching step, a glycerin bath step, and the like.

[0101] By forming the fiber bundle into a fiber bundle containing the porous fiber of the present invention, it is possible to obtain a fiber bundle that is easy to handle and exhibits high adsorption performance. When forming the fiber bundle, in order to prevent the porous fibers from repelling each other due to static electricity or the like and from losing their cohesion, and to prevent the single fibers from adhering to each other, the fiber bundle may be wrapped in a film, net, mesh, nonwoven fabric, or the like, or a processed yarn such as a covering yarn may be spirally wrapped around one or more fibers.

[0102] The adsorption column of the present invention includes a casing having ports at both ends communicating with the interior, and the fiber bundle of the present invention is housed in the casing. Examples of the shape of the casing include a rectangular or hexagonal tubular or cylindrical casing with both ends open.

[0103] Among these, a cylindrical body, especially a cylindrical body with a perfectly circular cross section in the radial direction, is preferred as the casing. This is because the casing has no corners, which prevents blood from accumulating at the corners. Furthermore, by making both ends of the casing open, the flow of the liquid to be treated is less likely to be disturbed, minimizing pressure loss.

[0104] The casing may be made of plastic, metal, or the like, and from the standpoints of cost, moldability, weight, blood compatibility, and the like, plastic is preferably used as the casing material.

[0105] When plastic is used as the material for the casing, a thermoplastic resin having excellent mechanical strength and thermal stability is preferably used, such as polycarbonate resin, cellulose resin, polyester resin, polyarylate resin, polyimide resin, cyclic polysulfone resin, polyethersulfone resin, polyolefin resin, polystyrene resin, polyvinyl alcohol resin, ABS resin, or a mixture thereof.

[0106] Among these, from the viewpoint of moldability and radiation resistance required for the casing, polypropylene, polystyrene, polycarbonate, ABS resin, or derivatives thereof are preferred as the material for the casing. In particular, resins with excellent transparency, such as polystyrene and polycarbonate, are advantageous in ensuring safety, since the internal state can be observed during perfusion of the liquid to be treated, for example.

[0107] Both ends of the casing are preferably physically sealed, for example, by disposing a mesh or by fixing the ends with a resin or the like and then penetrating the partition wall to provide through-holes that connect the inside and outside of the casing.

[0108] Here, the term "through hole" refers to an opening that penetrates the partition wall in the longitudinal direction of the porous fiber. That is, the through hole is a hole that exists in the partition wall and penetrates through it, and that connects the inside and outside of the casing separated by the partition wall.

[0109] Here, the "partition" refers to a portion at the end of the casing that separates the inside from the outside of the casing, and can be, for example, a resin that fixes the casing and the fibers. When using a resin as the partition, a resin liquid such as polyurethane is injected from both ends of the casing, and this resin liquid is hardened while flowing to the ends of the casing by centrifugal force, and then unnecessary portions are cut off.

[0110] Among the sealing methods, the method of arranging a mesh is preferred because it is easier to process than the method of forming a partition wall and it is easier to uniformly distribute the flow of the liquid to be treated within the column. Furthermore, for the purpose of further improving the dispersibility of the liquid to be treated within the column, a mesh with a large pressure loss, a plate-like member for controlling the flow called a baffle plate or a flow straightener, or the like may be provided in part of the mesh.

[0111] The fiber form when the fiber bundle is incorporated into the casing may be a form in which porous fibers are chopped into small pieces, or a form in which fibers are highly processed into knitted fabrics, woven fabrics, nonwoven fabrics, etc. Among these, a fiber bundle formed by bundling straight fibers is preferred, and it is preferable to insert this fiber bundle parallel to the longitudinal direction of the casing.

[0112] A fiber bundle made of straight porous fibers can easily ensure a flow path for the liquid being treated, making it easier to distribute the liquid evenly within the casing. It also reduces turbulence, which is advantageous in preventing increased pressure loss. Therefore, even when highly viscous blood is used as the liquid being treated, the risk of coagulation within the casing can be minimized.

[0113] The adsorption column of the present invention is capable of highly efficiently adsorbing target substances for adsorption and removal, primarily those with a molecular weight larger than albumin. Applications include filters for various fluids, regardless of whether they are in gas or liquid phase, adsorbents, heat insulators, sound absorbers, shock absorbers, cell culture substrates, and carriers for regenerative medicine. For example, the column is suitable for medical applications, such as the removal of pathogenic proteins from blood, plasma, and body fluids, and for the removal of impurities from raw material solutions of biopharmaceuticals in pharmaceutical purification, particularly in the purification process of biopharmaceuticals.

[0114] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. First, measurement methods and evaluation methods are described below.

[0115] (Method for Determining Peaks Derived from Microcrystals) In an SPring-8, BL03XU, second hatch, a porous fiber was fixed to an auto sample changer and irradiated with X-rays having a beam diameter of approximately 100 μm and a wavelength of 0.1 nm in the direction perpendicular to the fiber axis. The wide-angle X-ray scattering image obtained with the SOPHIAS detector was converted into a one-dimensional image using graph processing software Igor Pro (registered trademark, manufactured by WaveMetrics) so that the horizontal axis represents the scattering vector q and the vertical axis represents the X-ray scattering intensity.

[0116] The camera length is approximately 50 mm to 90 mm, and can be arbitrarily determined within a range that allows for observation of scattering originating from the target microcrystals. After one-dimensionalization, appropriate background removal was performed to ensure that only scattering originating from the porous fiber was observed. Specifically, background removal was performed by air scattering when there was nothing in the light path other than the porous fiber, and by scattering from the empty cell when the porous fiber was placed in a cell made of water or film to prevent drying, etc.

[0117] Furthermore, if the porous fiber contains a third component, such as fine particles other than organic polymers, the background from the scattering from the third component is also appropriately removed. The peaks in the scattering spectrum from which the background has been removed are assigned by literature or X-ray structural analysis, and if even one peak is assigned to a microcrystal, it is determined that microcrystals are present.

[0118] For example, the scattering vector of the amorphous peak of PMMA is q = 0.95 Å. －１ In the case of PMMA stereocomplex microcrystals, the stereocomplex peaks are q = 0.29, 0.84, and 1.14 Å. －１ It is known that there is a peak at (Macromolecules, 2021, 54, 2001-2010).

[0119] Therefore, q = 0.29, 0.84, 1.14 Å －１ Around (±0.05 Å －１ It is determined that microcrystals have been observed if there is at least one peak within the error range of 100. Furthermore, as shown in Figure 5, when a peak derived from microcrystals overlaps with a peak 110 derived from amorphous crystals, forming a shoulder peak 109 derived from microcrystals, it is also determined that microcrystals have been observed. In this case, peak separation is performed by fitting, and if a peak remains near the position of the peak derived from microcrystals in the residual after fitting the peak derived from amorphous crystals (i.e., it is convex upward), it can be determined that microcrystals are present.

[0120] For example, for PMMA stereocomplex crystallites, q = 0.95 Å －１ The residuals after fitting with the peak positions as －１ If at least one peak remains in the vicinity (is convex upward), it is determined that stereocomplex microcrystals are present.

[0121] Conversely, if the residual after fitting the amorphous peak does not show a peak at the position of the microcrystalline peak (it is not convex upward), it is determined that no microcrystalline exists. For example, for PMMA stereocomplex microcrystals, q = 0.95 Å －１The residuals after fitting with the peak positions as －１ When no peak remained at any position in the vicinity (no upward convexity), it was determined that no microcrystals were present.

[0122] When it is determined that a peak derived from microcrystals is present, the exact peak position of the peak derived from microcrystals is determined by fitting. For example, 0.84 Å －１ If there is a peak near q = 0.84 Å －１ The peak position is determined by fitting the peak position to the peak derived from other microcrystals (for example, q = 1.14 Å). －１ ) and amorphous origin q = 0.95 Å －１ When a peak also exists in the vicinity and forms a shoulder peak, the exact peak position of the peak derived from the microcrystals was determined by peak separation by fitting the multiple peaks present. The function used for fitting was a Gaussian function, and the fitting range was appropriately determined according to the width of the observed peak. In addition, background correction during fitting was performed using a linear function. The peak position was determined by q = ±0.05 Å. －１ If a peak was found within the error range, it was determined to be the peak in question.

[0123] (Average pore diameter near the outer surface of the fiber cross section) A sufficiently wetted porous fiber was placed in a container filled with water and frozen with liquid nitrogen to obtain a block with the porous fiber embedded in it. The block was sliced ​​to a thickness of 200 nm at a temperature of −65°C using an ultramicrotome equipped with a cryosystem to obtain a section in which the radial cross section of the porous fiber was exposed.

[0124] The obtained sections were freeze-dried in a vacuum dryer at 0.1 torr or less to sublimate the water, yielding dried samples. After that, a thin film of platinum-palladium (Pt-Pd) was formed on the sample surface by sputtering, and the sample was used for observation.

[0125] The fiber cross section of the sample was observed with a scanning electron microscope (S-5500 manufactured by Hitachi High-Technologies Corporation), and when an arbitrary straight line was drawn from the center point of the fiber cross section to the periphery, a region corresponding to 10% of the outer periphery was observed and imaged at a magnification (10,000 to 20,000 times) at which the pores could be sufficiently observed, excluding the small amount of dense layer present on the outermost surface.

[0126] After imaging, image analysis software (ImageJ) was used to perform binarization so that the pore portions were black and the structure portions were white, and the total area of ​​the pores was determined. If it was difficult to perform binarization of the pore and structure portions due to the contrast difference in the electron microscope image, a transparent sheet was placed on top of the printout and the pore portions were filled in black using a black pen or the like. Then, using an image obtained by copying the transparent sheet onto white paper, binarization was performed so that the pore portions were black and the structure portions were white.

[0127] It should be noted that black portions with five or fewer consecutive pixels were treated as white portions, which are structures, because it was impossible to distinguish between noise and pores. The equivalent circle diameter, which is the diameter of a circle having the same area, was calculated from the area of ​​each pore, and the obtained equivalent circle diameters were arranged in descending order. The areas of the pores were added up in descending order of the equivalent circle diameter, and the equivalent circle diameter of the pore when the sum exceeded half of the total area of ​​all the pores was taken as the cross-sectional pore diameter.

[0128] The cross-sectional pore diameters were calculated in the same manner at three arbitrary locations in the region near the outer surface, and the average value was used as the average pore diameter near the outer surface of the fiber cross section. The average pore diameter was rounded to one decimal place.

[0129] (Average pore diameter near the center of the fiber cross section) The same procedure as in the above-mentioned "average pore diameter near the outer surface of the fiber cross section" was performed, except that the area to be observed and photographed was near the center of the porous fiber, and the average pore diameter near the center of the fiber cross section was calculated.

[0130] (Average pore size in the middle region of the fiber cross section) The same procedure as in the above-mentioned "average pore size near the outer surface of the fiber cross section" was performed, except that the region to be observed and photographed was the middle region of the porous fiber, and the average pore size in the middle region of the fiber cross section was calculated.

[0131] (Average pore size of fiber cross section) A line is drawn from the center point of the fiber cross section to the periphery, and the line is divided into 10 equal parts to divide the fiber cross section into 10 small regions. The average pore size of each small region is calculated in order from the closest to the center point. １ ~R １０ , the area of ​​each small region is S １ ~S １０ When this is the case, the average pore size of the fiber cross section is expressed by the following formula (1).

[0132]

[0133] Average pore diameter R of each small area ｊ is calculated in the same manner as in the above-mentioned "average pore diameter near the outer surface of the fiber cross section," except that the areas to be observed and photographed are each small area.

[0134] (Opening rate of the outer surface of the fiber) A sufficiently wetted porous fiber was frozen in liquid nitrogen and freeze-dried in a vacuum dryer at 0.1 torr or less for 24 hours to sublimate the water, thereby obtaining a dried sample. A thin film of platinum-palladium (Pt-Pd) was then formed on the sample surface by sputtering, and a surface observation sample was prepared.

[0135] The fiber surface of the surface observation sample was observed using a scanning electron microscope (S-5500 manufactured by Hitachi High-Technologies Corporation), and an arbitrary position on the fiber surface was imaged. The magnification was set to a value (5,000 to 10,000 times) at which pores could be clearly seen. After imaging, the pores contained in each image were measured, and the total area of ​​all pores was calculated.

[0136] The total area of ​​all pores was determined by binarizing the electron microscope image using the image analysis software "ImageJ" so that the pores were black and the non-pores were white. The obtained image was analyzed and the total area of ​​all pores was calculated. If it was difficult to binarize the pore and non-pore portions due to the contrast difference in the electron microscope image, a transparent sheet was placed on top of the printout and the pores were filled in black using a black pen or the like. Then, an image of the transparent sheet copied onto white paper was used, and binarization was performed so that the pores were black and the non-pores were white, and analysis was performed.

[0137] The pore area of ​​the outer surface of the fiber was calculated from the total area of ​​all the obtained pores and the area of ​​the entire image using the following formula (2). This measurement was performed at nine locations spaced 1 cm or more apart in the longitudinal direction of the fiber, and the values ​​were averaged and rounded to one decimal place.

[0138] Open area of ​​the outer surface of the fiber (%) = total area of ​​all pores (μm ２ ) / total image area (μm ２ ) × 100 Equation (2) (Average pore diameter on the outer surface of the fiber) Using the binarized image obtained in the above-mentioned "Open area ratio on the outer surface of the fiber," the circle-equivalent diameter was calculated from the area of ​​each pore, the circle-equivalent diameters were arranged in descending order, and the areas of the pores were added up in descending order of the circle-equivalent diameter. When the sum exceeded half of the total area of ​​all the pores, the circle-equivalent diameter of the pore was defined as the surface pore diameter.

[0139] The equivalent circle diameters were calculated in the same manner using nine or more images spaced 1 cm or more apart in the longitudinal direction of the fiber, and the average value was used as the average pore diameter on the outer surface of the fiber. The average pore diameter on the outer surface of the fiber was rounded to one decimal place.

[0140] (Aspect ratio of the major axis to the minor axis of pores on the outer surface of the fiber) Using the binarized images obtained in the above "Open area ratio of the outer surface of the fiber," 15 or more pores per image were fitted with ellipses to calculate the major axis / minor axis ratio. Similar measurements were performed on 9 or more images spaced 1 cm or more apart in the longitudinal direction of the fiber, and the values ​​were averaged to calculate the aspect ratio of the major axis to the minor axis of pores on the outer surface of the fiber.

[0141] (Viscosity of spinning dope) The viscosity is measured in a constant temperature bath set at a high temperature according to JIS Z 8803 (2011 edition) by the falling ball method. Specifically, a viscosity tube with an inner diameter of 40 mm is filled with the spinning dope, a steel ball with a diameter of 2 mm (made of SUS316) is dropped into the dope, and the time required for the steel ball to fall 200 mm is measured. The temperature during measurement is 110°C.

[0142] (Gelation point of spinning dope) The gelation point of the spinning dope was determined as the temperature at which the viscosity suddenly increased when the viscosity measurement temperature was decreased in 5° C. intervals from 110° C. in the above-mentioned "Viscosity of spinning dope." Specifically, the gelation point was determined as the temperature at which the viscosity reached 10 times or more the viscosity at 110° C.

[0143] (Ultra-small angle X-ray scattering of spinning dope) A through-hole was drilled in a silicone rubber sheet having a thickness of 0.5 mm, and the spinning dope was sealed in a measurement cell covered on both sides with Kapton films. The measurement cell containing the spinning dope was fixed to a cooling and heating stage (Linkam Co., Ltd.) in an SPring-8 BL03XU second hatch.

[0144] The measurement cell was heated to 110°C, and then cooled at a rate of 5°C / min. The cell was irradiated 20 times with X-rays having a beam diameter of approximately 100 µm and a wavelength of 0.2 nm at 1-minute intervals. The camera length was 7.82 m, the integration time was 10 s, and the attenuator was Al25 nm.

[0145] The ultra-small angle X-ray scattering image obtained with the PILATUS detector was converted into a one-dimensional image using graph processing software Igor Pro (registered trademark, manufactured by WaveMetrics), and a double logarithmic graph was created with the horizontal axis representing the scattering vector q and the vertical axis representing the scattering intensity.

[0146] For a reference in which only the solvent of the spinning dope was sealed in the measurement cell, ultra-small angle X-ray scattering was measured under the same conditions, and background processing was performed. －１ In the following regions, it was determined that X-ray scattering was observed when there was a region where the scattering intensity increased as q decreased, as shown in FIG.

[0147] (Spinnability) The spinnability was evaluated as follows: ◯: When the porous fiber was wound at a spinning speed of 5 m / min, 150 m of the fiber could be wound without thread breakage. △: When the porous fiber was wound at a spinning speed of 5 m / min, 1 to 3 thread breakages occurred in 150 m of the fiber. ×: When the porous fiber was wound at a spinning speed of 5 m / min, 4 or more thread breakages occurred in 150 m of the fiber.

[0148] (Dispersion component of surface free energy) The freeze-dried porous fiber was packed into a glass column, and the dispersion component of the surface free energy was measured and calculated using a surface free energy measurement device iGC-SEA manufactured by Japan Science Core Co., Ltd., with reference to the method described in "Inverse gas chromatography applications: A review" Adv. Colloid Interface Sci., 212, 21-44 (2014). Specifically, a linear alkane having 6 to 9 carbon atoms was used as the test solvent, and the retention volume was calculated from the obtained chromatogram. The dispersion component of the surface free energy was calculated from the retention volume of various alkanes.

[0149] (Adsorption performance of porous fiber) The porous fiber is adsorbed at 0.01 to 0.10 g / mm ２ The porous fiber was fixed and cut under tension, thereby obtaining a section in which the radial cross section of the porous fiber was exposed. The cut section was photographed under magnification using an optical microscope, and the perimeter P (cm) of the fiber cross section was calculated by tracing the outer periphery using image analysis software.

[0150] 200 pieces of porous fiber were cut into a length of 5.5 cm in the longitudinal direction of the fiber and then chopped into small pieces to prepare samples for adsorption tests. The total surface area S (cm ２ ) was calculated using the following formula (3-1):

[0151] S (cm ２ ) = P (cm) × 5.5 (cm) × 200 ... Equation (3-1) An adsorption test sample having the above total surface area was placed in a 5 mL container, and 2.6 mL of commercially available human plasma was added thereto. Using a seesaw shaker (TAITEC Wave-SI) set to 38 on the scale and at the maximum angle (one reciprocation every 1.7 seconds), the sample was shaken and stirred at 37°C for 4 hours. 1 mL of the human plasma was sampled before contact with the porous fiber and after stirring was completed.

[0152] LDL cholesterol was measured by the direct method, and the LDL cholesterol concentration C1 (mg / ml) in human plasma before contact with the porous fiber and the LDL cholesterol concentration C2 (mg / ml) after stirring were determined, and the adsorption amount per fiber surface area was calculated using the following formula (3-2).

[0153] The amount of LDL cholesterol adsorbed per fiber surface area (mg / cm ２ )=(C1-C2)(mg / ml)×2.6(mL) / S(cm ２ ) Equation (3-2) Each adsorption amount was measured three times and averaged, and the average was rounded to two decimal places.

[0154] [Example 1] A spinning dope was prepared by mixing 200 parts by weight of syn-PMMA having a weight-average molecular weight of 1,400,000, 40 parts by weight of iso-PMMA having a weight-average molecular weight of 500,000, 1,560 parts by weight of DMSO, and 170 parts by weight of formamide so that the PMMA concentration was 12% by weight. The gel point of the obtained spinning dope was 90°C, and the viscosity at 110°C was 175.5 Pa s.

[0155] The spinning dope was extruded into the air using a circular nozzle. The nozzle temperature was 95°C. The dry length, i.e., the length of the free-running section, was 50 cm. The cold air velocity during free-running was 30 m / s. ３ The fiber was cooled at 1000 W / h. Thereafter, the fiber was introduced into a coagulation bath consisting of water at 60° C. The obtained porous fiber was washed with water in a 40° C. water bath, and then introduced into a bath containing a 70 wt % aqueous glycerin solution for moisture retention. The porous fiber was passed through a heat treatment bath at 85° C. to remove excess glycerin, and then wound up at 20 m / min to obtain porous fiber 1.

[0156] [Example 2] A spinning dope was prepared by mixing 200 parts by weight of syn-PMMA having a weight-average molecular weight of 1,400,000, 40 parts by weight of iso-PMMA having a weight-average molecular weight of 500,000, 1,627 parts by weight of DMSO, and 88 parts by weight of 1,4-butanediol so that the PMMA concentration was 12% by weight. The gel point of the obtained spinning dope was 75°C, and the viscosity at 110°C was 201.0 Pa s.

[0157] The spinning dope was extruded into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The cold air velocity during free-running was 30 m / s. ３The fiber was cooled at 100° C. / h. Thereafter, the fiber was introduced into a coagulation bath consisting of water at 60° C. The obtained porous fiber was washed with water in a 40° C. water bath, and then introduced into a bath containing a 70 wt % aqueous glycerin solution to keep the fiber moist. The porous fiber was then passed through a heat treatment bath at 85° C. to remove excess glycerin, and then wound up at 20 m / min to obtain porous fiber 2.

[0158] [Example 3] A spinning dope was prepared by mixing 200 parts by weight of syn-PMMA having a weight-average molecular weight of 1,400,000, 40 parts by weight of iso-PMMA having a weight-average molecular weight of 500,000, 1,627 parts by weight of DMSO, and 88 parts by weight of propylene glycol so that the PMMA concentration was 12% by weight. The gel point of the obtained spinning dope was 75°C, and the viscosity at 110°C was 242.0 Pa s.

[0159] The spinning dope was extruded into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The cold air velocity during free-running was 30 m / s. ３ The fiber was cooled at 100° C. / h. Thereafter, the fiber was introduced into a coagulation bath consisting of water at 60° C. The obtained porous fiber was washed with water in a 40° C. water bath, and then introduced into a bath containing a 70 wt % aqueous glycerin solution for moisture retention. The porous fiber was passed through a heat treatment bath at 85° C. to remove excess glycerin, and then wound up at 20 m / min to obtain porous fiber 3.

[0160] [Example 4] A spinning dope was prepared by mixing 200 parts by weight of syn-PMMA having a weight-average molecular weight of 1,400,000, 40 parts by weight of iso-PMMA having a weight-average molecular weight of 500,000, 1,627 parts by weight of DMSO, and 88 parts by weight of glycerin so that the PMMA concentration was 12% by weight. The gel point of the obtained spinning dope was 75°C, and the viscosity at 110°C was 230.0 Pa s.

[0161] The spinning dope was extruded into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The cold air velocity during free-running was 33 m / s. ３ The fiber was cooled at 100° C. / h, and then introduced into a coagulation bath of water at 70° C. The resulting porous fiber was washed in a water bath at 40° C., then introduced into a bath containing a 70 wt % aqueous glycerin solution to keep it moist, passed through a heat treatment bath at 85° C. to remove excess glycerin, and then wound up at 20 m / min to obtain porous fiber 4.

[0162] [Example 5] Cool air speed: 36 m ３ The same procedure as in Example 4 was carried out except that the time for coagulation was 1000 kJ / h and the coagulation bath temperature was 60°C, thereby obtaining porous fiber 5.

[0163] [Example 6] A spinning dope was prepared by mixing 178 parts by weight of syn-PMMA having a weight-average molecular weight of 1.4 million, 36 parts by weight of iso-PMMA having a weight-average molecular weight of 500,000, 2362 parts by weight of DMSO, and 184 parts by weight of glycerin so that the PMMA concentration was 7.8% by weight. The gel point of the obtained spinning dope was 60°C, and the viscosity at 110°C was 25.9 Pa s.

[0164] The spinning solution was discharged into the air using a syringe pump. The syringe temperature was 90°C. The length of the free-running section was 70 cm. The cold air velocity during free-running was 30 m / s. ３ The fiber was cooled at 1000 W / h, and then introduced into a coagulation bath of water at 60° C. The resulting porous fiber was washed in a water bath at 40° C., and then introduced into a bath containing a 70 wt % aqueous glycerin solution to keep it moist. The fiber was then passed through a heat treatment bath at 85° C. to remove excess glycerin, and then wound up at 3 m / min to obtain porous fiber 6.

[0165] [Example 7] Winding speed: 10 m ３ The same procedure as in Example 5 was carried out except that the time was changed to / h, and porous fiber 7 was obtained.

[0166] [Example 8] Winding speed: 3 m ３ The same procedure as in Example 5 was carried out except that the time was changed to / h, and porous fiber 8 was obtained.

[0167] [Example 9] A spinning dope a for forming region A was prepared by mixing 40.9 parts by mass of syn-PMMA having a weight average molecular weight of 1,400,000, 6.8 parts by mass of iso-PMMA having a weight average molecular weight of 500,000, and 428 parts by mass of dimethyl sulfoxide (hereinafter referred to as "DMSO") so that the PMMA concentration was 10% by mass, and stirring the mixture at 110°C for 8 hours. The viscosity of the obtained spinning dope at 110°C was 190 poise.

[0168] Similarly, as the spinning solution b for forming region B, so that the PMMA concentration is 15% by mass, 31.7 parts by mass of syn-PMMA having a weight average molecular weight of 400,000, 31.7 parts by mass of syn-PMMA having a weight average molecular weight of 1.4 million, 16.7 parts by mass of iso-PMMA having a weight average molecular weight of 500,000, 20 parts by mass of PMMA copolymer having a molecular weight of 300,000 containing 1.5 mol% of sodium parastyrenesulfonate having a sulfo group exhibiting a negative charge, 376 parts by mass of DMSO were mixed, and stirred at 110 ° C. for 8 hours to prepare a stock solution. The viscosity of the obtained spinning solution at 110 ° C. was 102 poise.

[0169] Using a concentric sheath-core spinneret, spinning dope a and spinning dope b were simultaneously extruded into the air at a rate of 1.0 cc / min, with the dope a forming the sheath and the dope b forming the core. The spinneret temperature was 99°C. The length of the free-running section was 55 cm, and the free-running time was 0.72 seconds. The fiber was cooled with a cold air speed of 7.5 m / sec during free-running. The fiber was then introduced into a coagulation bath containing a 20% by mass DMSO aqueous solution at 60°C. The resulting composite porous fiber was washed with water in a 40°C water bath, then introduced into a bath containing a 70% by mass glycerin aqueous solution for moisture retention, passed through a heat treatment bath at 85°C to remove excess glycerin, and wound up at 20 m / min to obtain porous fiber 9.

[0170] [Comparative Example 1] A spinning dope was prepared by mixing 171 parts by weight of syn-PMMA having a weight-average molecular weight of 1.4 million, 34 parts by weight of iso-PMMA having a weight-average molecular weight of 500,000, 2159 parts by weight of DMSO, and 263 parts by weight of glycerin so that the PMMA concentration was 7.8% by weight. The gel point of the obtained spinning dope was 65°C, and the viscosity at 110°C was 107.7 Pa s.

[0171] The spinning solution was discharged into the air using a syringe pump. The syringe temperature was 90°C. The length of the free-running section was 70 cm. The cold air velocity during free-running was 30 m / s. ３ The fiber was cooled at 100°C / h. Thereafter, the fiber was introduced into a coagulation bath consisting of water at 60°C. The obtained porous fiber was washed with water in a 40°C water bath, and then introduced into a bath containing a 70 wt% aqueous glycerin solution to keep it moist. After passing through a heat treatment bath at 85°C to remove excess glycerin, the fiber was wound up at 3 m / min to obtain porous fiber 9. Frequent yarn breakage occurred, and the spinnability was poor.

[0172] [Comparative Example 2] A spinning dope was prepared by mixing 290 parts by weight of syn-PMMA having a weight-average molecular weight of 1.4 million, 58 parts by weight of iso-PMMA having a weight-average molecular weight of 500,000, and 2,554 parts by weight of DMSO so that the PMMA concentration was 12% by weight. The gel point of the obtained spinning dope was 65°C, and the viscosity at 110°C was 154.6 Pa s.

[0173] The spinning dope was extruded into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The cold air velocity during free-running was 30 m / s. ３ The fiber was cooled at 100° C. / h, and then introduced into a coagulation bath of water at 60° C. The resulting porous fiber was washed in a water bath at 40° C., then introduced into a bath containing a 70 wt % aqueous glycerin solution to keep it moist, and passed through a heat treatment bath at 85° C. to remove excess glycerin. The fiber was then wound up at 20 m / min, and a porous fiber 10 was obtained.

[0174] [Comparative Example 3] A spinning dope was prepared by mixing 31.7 parts by weight of syn-PMMA having a weight average molecular weight of 400,000, 31.7 parts by weight of syn-PMMA having a weight average molecular weight of 1,400,000, 16.7 parts by weight of iso-PMMA having a weight average molecular weight of 500,000, 20 parts by weight of PMMA copolymer having a molecular weight of 300,000 containing 1.5 mol% of sodium parastyrenesulfonate having a sulfo group exhibiting a negative charge, and 376 parts by weight of DMSO, so that the PMMA concentration was 21% by weight. The gel point of the obtained spinning dope was 70 ° C., and the viscosity at 110 ° C. was 423.0 Pa s.

[0175] The spinning dope was extruded into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The cold air velocity during free-running was 30 m / s. ３ The fiber was cooled at 1000 W / h. Thereafter, the fiber was introduced into a coagulation bath consisting of water at 40° C. The obtained porous fiber was washed with water in a 40° C. water bath, and then introduced into a bath containing a 70 wt % aqueous glycerin solution for moisture retention. The porous fiber was passed through a heat treatment bath at 85° C. to remove excess glycerin, and then wound up at 20 m / min to obtain porous fiber 11.

[0176] [Comparative Example 4] Cool air speed: 42 m ３The same procedure as in Example 5 was carried out except that the time was changed to / h, and porous fiber 12 was obtained.

[0177] [Comparative Example 5] A spinning dope was prepared by mixing 168 parts by weight of syn-PMMA having a weight-average molecular weight of 1,400,000, 34 parts by weight of iso-PMMA having a weight-average molecular weight of 500,000, 2,167 parts by weight of DMSO, and 329 parts by weight of formamide so that the PMMA concentration was 7.5% by weight. The viscosity of the obtained spinning dope at 110°C was too high to measure.

[0178] The spinning solution was discharged into the air using a syringe pump. The syringe temperature was 90°C. The length of the free-running section was 70 cm. The cold air velocity during free-running was 30 m / s. ３ The fiber was cooled at 0.3 m / min. / h. Thereafter, it was introduced into a coagulation bath consisting of water at 60°C. The obtained porous fiber was washed with water in a 40°C water bath, then introduced into a bath containing a 70 wt% glycerin aqueous solution for moisture retention, passed through a heat treatment bath at 85°C to remove excess glycerin, and then wound up at 3 m / min to obtain porous fiber 13. Many yarn breaks occurred and the spinnability was poor. [Comparative Example 6] The length of the free running section was 0.3 cm, and the amount of cold air was 0 m ３ The same procedure as in Example 5 was carried out except that the time was changed to / h, and porous fiber 14 was obtained.

[0179] The spinning conditions obtained in Examples 1 to 9 are shown in Table 1, and the spinning conditions in Comparative Examples 1 to 6 are shown in Table 2. The evaluation results of Examples 1 to 9 are shown in Table 3, and the evaluation results of Comparative Examples 1 to 6 are shown in Table 4.

[0180]

[0181]

[0182]

[0183]

[0184] The porous fiber of the present invention can be used as a filter for various fluids, regardless of whether they are in a gas or liquid phase, as an adsorbent, a heat insulator, a sound absorber, an impact buffer, a cell culture substrate, a carrier for regenerative medicine, etc. In particular, it is suitable for use in medical applications, such as the removal of pathogenic proteins from blood, plasma, and body fluids, and for the removal of impurities from solutions of raw materials for biopharmaceuticals, in the production of biopharmaceuticals.

[0185] 100 ... Virtual region 1 101 ... Virtual region 2 102 ... Virtual region boundary 103 ... Perpendicular to the tangent at any point of the virtual region boundary 104 ... Boundary of region 1 105 ... Boundary of region 2 106 ... Region boundary 107 ... Region 1 108 ... Region 2 109 ... Shoulder peak derived from microcrystals 110 ... Peak derived from amorphous

Claims

1. A porous fiber comprising an organic polymer, the average pore size in the fiber cross section is 100-1,000 nm, the average pore size on the outer surface of the fiber is 100-10,000 nm, and when the average pore size in the middle region of the fiber cross section is Rm and the average pore size near the center is Ri, Rm / Ri = 0.85-1.15, and the porosity of the outer surface of the fiber is 5-50%.

2. The porous fiber according to claim 1, wherein the porosity of the outer surface of the fiber is 5 to 40%.

3. The porous fiber according to claim 1, wherein the aspect ratio of the major axis to the minor axis of the pores on the outer surface of the fiber is 1.5 to 10.

4. The dispersion component of the surface free energy is 5 to 100 mJ / m ２ 2. The porous fiber according to claim 1, wherein 5. The porous fiber according to claim 1, wherein the organic polymer is an amorphous polymer.

6. The porous fiber according to claim 5, wherein the amorphous polymer is an acrylic polymer.

7. The porous fiber according to claim 5, wherein said amorphous polymer is polymethyl methacrylate.

8. The porous fiber according to claim 1, wherein the cross section of the fiber has Region A and Region B separated by a region boundary, Region A has a uniform structure with an average pore size Ap of 100 to 1000 nm, and Region B has an average pore size Bp smaller than Ap or is non-porous.

9. The porous fiber of claim 1, wherein said porous fiber is a solid fiber.

10. A fiber bundle comprising the porous fiber of claim 1.

11. An adsorption column comprising the fiber bundle of claim 10.

12. The adsorption column according to claim 11, which is used for blood purification.

13. A method for producing a pharmaceutical product, comprising a purification step using the adsorption column according to claim 10.

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