Porous fibers, fiber bundle and adsorption column

Abstract

To provide a porous fiber, a fiber bundle, and an adsorption column having a fiber bundle, which have a high mechanical strength and excellent spinnability even when a pore diameter of the fiber is large.SOLUTION: A porous fiber of the present invention contains an amorphous polymer, has an average pore size in a fiber cross section of 100 to 1,000 nm, and exhibits a scattering vector (q) peak derived from a microcrystal of the amorphous polymer in a range of 0.2<q<1.2Å-1 as determined by wide-angle X-ray scattering measurement.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to porous fibers, fiber bundles, and adsorption columns. [Background technology]

[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 discloses porous solid fibers made of crystalline polymers such as polyethylene and polypropylene, and amorphous polymers such as polysulfone, polystyrene, and polymethyl methacrylate, which adsorb components in body fluids. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Publication No. 58-76104 [Patent Document 2] Japanese Patent Application Laid-Open No. 2014-207989 [Patent Document 3] International Publication No. 2017 / 188119 [Patent Document 4] Japanese Patent Application Publication No. 6-296860 Summary of the Invention [Problem to be solved by the invention]

[0007] However, the hollow fiber separation membrane described in Patent Document 1 differs in its design concept from the others in that it utilizes its hollow shape to remove proteins by separation. Furthermore, in order to efficiently adsorb and remove high-molecular-weight proteins, it is necessary to design the pore size to be large. However, the larger the pore size, the lower the fiber density and the lower the mechanical strength. Patent Document 1 does not describe controlling the amorphous polymer-derived microcrystals contained in the fibers to solve the problem of poor spinnability due to a decrease in mechanical strength.

[0008] There is no description of the porous solid fibers described in Patent Documents 2 and 3 being able to efficiently adsorb and remove high-molecular-weight proteins larger than albumin, a medium-molecular-weight protein. Therefore, there is no description of how to solve the problem of poor spinnability caused by large pore sizes.

[0009] Patent Document 4 cites examples of porous solid fibers made from crystalline polymers and amorphous polymers, but does not disclose any control of the microcrystals of amorphous polymers to improve the deterioration of spinnability, which is a concern particularly in amorphous polymers whose fibers have weak mechanical strength.

[0010] Therefore, an object of the present invention is to provide porous fibers, fiber bundles, and adsorption columns having fiber bundles that can efficiently adsorb high-molecular-weight substances to be removed that are larger than albumin, which is the main substance contained in the treated liquid, i.e., substances with molecular weights of tens of thousands or more, or molecular sizes of several nm or more.

[0011] 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. [Means for solving the problem]

[0012] The present invention has the following configurations (1) to (10) for solving the above problems. (1) The fiber contains an amorphous polymer, has an average pore size of 100 to 1000 nm in the cross section, and has a peak of the scattering vector (q) derived from the crystallites of the amorphous polymer obtained by wide-angle X-ray scattering measurement of 0.2 <q<1.2Å -1 Porous fibers present in (2) The peaks of the scattering vectors originating from the microcrystals of the above amorphous polymer are q = 0.29, 0.84, and 1.14 Å. -1 The porous fiber according to (1), which is present in any one of the above. (3) The porous fiber according to (1) or (2), wherein the amorphous polymer contains a syndiotactic isomer and an isotactic isomer, and the peak of the scattering vector (q) is derived from a stereocomplex structure obtained by mixing the syndiotactic isomer and the isotactic isomer. (4) The porous fiber according to any one of (1) to (3), wherein the amorphous polymer is polymethyl methacrylate. (5) The porous fiber according to any one of (1) to (4), wherein the porous fiber is a solid fiber. (6) A fiber bundle having the porous fiber according to any one of (1) to (5). (7) A liquid treatment column having the fiber bundle described in (6). (8) A method for producing a spinning solution by dissolving an amorphous polymer in a solvent to obtain a spinning solution, a discharge step of heating the spinning solution to a gel point or higher and discharging it from a spinneret, and a cooling step of cooling the spinning solution to a gel point or lower in a dry section after discharging it from the spinneret, wherein the spinning solution 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 A method for producing porous fibers having scattering below. (9) The method for producing a porous fiber according to (8), wherein the solvent includes a good solvent and a poor solvent for the amorphous polymer. (10) The method for producing a porous fiber according to (9), wherein the amorphous polymer is a polymer containing a functional group having hydrogen bond donor properties, and the poor solvent is a compound having hydrogen bond acceptor properties. [Effects of the Invention]

[0013] 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. [Brief explanation of the drawings]

[0014] [Figure 1] This is an example of an X-ray scattering spectrum in which a peak derived from microcrystals overlaps with a peak derived from amorphous matter, forming a shoulder peak. [Figure 2] 1 is an example of an ultra-small angle X-ray scattering spectrum of a spinning dope when X-ray scattering is measured. DETAILED DESCRIPTION OF THE INVENTION

[0015] The porous fiber, fiber bundle, and adsorption column of the present invention will be described in detail below.

[0016] The porous fiber of the present invention contains an amorphous polymer, has an average pore size in the fiber cross section of 100 to 1000 nm, and has a peak of a scattering vector (q) derived from microcrystals of the amorphous polymer that is obtained by wide-angle X-ray scattering measurement of 0.2 <q<1.2Å -1 It is characterized by being present in

[0017] "Fiber cross section" refers to a plane perpendicular to the longitudinal direction of the porous fiber of the present invention.

[0018] 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.

[0019] 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.

[0020] 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 pore clogging and utilizing the interior of the porous fiber for highly efficient adsorption, the following two designs are preferred.

[0021] That is, it is preferable to design each average pore size to be larger than the size of the substance to be 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.

[0022] 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 are described below, and have molecular weights of several hundred thousand to several million and sizes of about 15 to 100 nm.

[0023] 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, it 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.

[0024] Furthermore, from the viewpoint of highly efficient adsorption of the target substances for adsorption and removal, the average pore diameter in 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 in 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 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.

[0025] In the "average pore size of the fiber cross section" of the present invention, it is preferable that the average pore size Rm of the intermediate region located between the outer surface and the center of the fiber is approximately the same as the average pore size Ri near the center in order to efficiently adsorb the substances to be adsorbed and removed.

[0026] 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, but when target substances are removed by adsorption, it is preferable that the pore size suitable for adsorbing the target substance be uniformly distributed from the middle region of the fiber to near the center, in order to enable highly efficient adsorption. Specifically, the ratio Rm / Ri is preferably 0.85 to 1.15, and more preferably 0.90 to 1.10.

[0027] On the other hand, in the "average pore size of the fiber cross section" of the present invention, it is preferable 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.

[0028] 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.

[0029] 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, if 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.

[0030] 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, if 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.

[0031] In porous fibers, the "near the outer surface" refers to the region close to the outer periphery of the porous fiber, which corresponds to 10% of the outer periphery when a 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 where 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.

[0032] 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 the area in the cross section of the fiber where there are no pores with a pore size of 15 nm or more.

[0033] In porous fibers, the "near-center" refers to the 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.

[0034] The term "intermediate region" refers to a region located midway between the center of a porous fiber and the outer surface of the fiber. Specifically, when a straight line is drawn from the center point of the fiber cross section to the periphery and the cross section of the fiber 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.

[0035] 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 that discharges the spinning dope.

[0036] When the porous fiber is a hollow fiber, the terms "near the outer surface," "near the center," and "middle 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 "middle region" refers to the fifth small region closest to the center.

[0037] 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.

[0038] 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, but it is preferable that the porous fiber does not contain the third component because doing so may reduce the mechanical strength of the porous fiber, reduce the efficiency of cleaning during spinning, or cause the third component to leach out from the inside of the porous fiber to the outside.

[0039] 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 several 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.

[0040] It is also possible to immobilize multiple ligands that specifically interact with the substance to be adsorbed and removed on the surface 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.

[0041] The materials of the outer surface region and the center region of the porous fiber of the present invention may be the same or different. However, from the viewpoint of preventing peeling and deformation of the porous fiber due to differences in physical or chemical properties caused by differences in materials, it is preferable that the materials of each region are the same. From the viewpoint of achieving both blood compatibility and adsorption performance, it is desirable that the outer surface of the fiber and the surfaces of the pores inside the fiber have an appropriate degree of hydrophobicity. The hydrophobicity can be quantified by the dispersion component of the surface free energy, and specifically, the dispersion component of the surface free energy measured by inverse gas chromatography is 5 to 100 mJ / m 2It is preferable that the concentration is 10 to 80 mJ / m 2 , and more preferably 20 to 70 mJ / m 2 is.

[0042] The material for the porous fiber of the present invention includes amorphous polymers from the viewpoints of moldability, cost, etc.

[0043] Here, "amorphous polymers" are polymers that solidify when the temperature is lowered from a molten state, with the molecules remaining irregularly entangled. Compared to crystalline polymers, amorphous polymers are particularly superior 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. Furthermore, in terms of the physical and chemical properties of porous fibers, amorphous polymers are easy to handle as materials.

[0044] Examples of amorphous polymers include polymethyl methacrylate (hereinafter referred to as "PMMA"), polyacrylonitrile (hereinafter referred to as "PAN"), polyacrylamide, polysulfone, polyethersulfone, polyarylethersulfone, polystyrene, polycarbonate, and derivatives thereof.

[0045] Among these, PMMA, PAN, polysulfone, polyethersulfone, polystyrene, etc., which have an appropriate hydrophobic interaction, are preferably used. Among amorphous polymers, PMMA is particularly preferred because it has an appropriate hydrophobicity, excellent mechanical strength, and can withstand radiation sterilization when used in medical applications.

[0046] The porous fiber of the present invention is more preferably composed mainly of an amorphous polymer. Here, "composed mainly of an amorphous polymer" means that the amorphous polymer accounts for 50% by weight or more of the total components constituting the porous fiber.

[0047] It has been discovered that the presence of microcrystals derived from amorphous polymers in the porous fibers of the present invention is important for obtaining porous fibers 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 partial crystallization can occur using 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 can form.

[0048] 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.

[0049] X-ray scattering is used as a method for analyzing crystal structure. Wide-angle X-ray scattering (hereinafter referred to as "WAXS") using high-intensity synchrotron radiation facilities (e.g., SPring-8) is particularly preferred because of its high sensitivity compared to laboratory-level X-ray diffraction instruments (e.g., Rigaku's SmartLab).

[0050] To determine whether microcrystals are present in porous fibers, if they are known microcrystals, their presence can be determined by comparing them with literature that lists the X-ray scattering data for those microcrystals and finding peaks at the peak positions of those originating from microcrystals.If the microcrystals are unknown, X-ray structural analysis can be performed on the diffraction pattern obtained by WAXS to determine whether the peaks are originating from microcrystals.

[0051] In the present invention, in order to achieve excellent spinnability despite the large pore size and highly efficient adsorption of high-molecular-weight proteins and other substances contained in the treated liquid, it is important that the inter-crystalline lattice distance (d) of the microcrystals be within an optimal range. The scattering vector q and the inter-crystalline lattice distance d have the relationship q = 2π / d.

[0052] 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 important that the distance between the crystal lattices of amorphous polymers is less than 0.05 mm. This means that the intercrystalline distance d between the crystal lattices of amorphous polymers is relatively large compared to the folded crystal structure commonly seen in crystalline polymers. In other words, because the polymers have a more complex crystalline structure, it is difficult to form crystals. However, once microcrystals are formed using methods such as hydrogen bonding (described below), the entanglement between the amorphous polymers becomes a stable crystalline structure that is difficult to unravel, resulting in porous fibers with high mechanical strength.

[0053] On the other hand, if the crystal lattice distance is too large, it becomes difficult to form microcrystals. Therefore, the porous fiber of the present invention has a scattering vector (q) peak of 0.2 Å derived from the microcrystals of the amorphous polymer obtained by WAXS X-ray structural analysis. -1 There are more than

[0054] In particular, microcrystals are easily formed, resulting in high mechanical strength. Therefore, 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.

[0055] 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 the end groups. Among them, PMMA is particularly preferred because, despite being an amorphous polymer, it has different optical isomers, namely, syndiotactic and isotactic isomers, which form a stereocomplex.

[0056] 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.

[0057] Furthermore, the pores on the outer surface of the fiber of the present invention preferably have an aspect ratio of the major axis (the longest radius of the pore) to the minor axis (the shortest radius of the pore) within a certain range. 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 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.

[0058] The porosity and aspect ratio of the outer surface 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.

[0059] Solution spinning is preferably used as a method for producing the porous fiber of the present invention. While it is possible to make composite fibers obtained by melt spinning porous by post-treatment such as drawing or extraction, when attempting to obtain porous fibers containing amorphous polymers as in the present invention and having an average cross-sectional pore size of 100 nm or more, the risk of breakage or delamination is high, making stable spinning difficult. On the other hand, solution spinning allows fibers with the desired porous structure to be obtained by uniformly dissolving the fiber material in a solvent and then removing the solvent. Furthermore, since post-treatment for making the fibers porous, as in melt spinning, is not required, productivity is excellent and there is very little risk of delamination or breakage. For these reasons, solution spinning is used as a method for producing the porous fiber of the present invention.

[0060] In addition, in order to control the surface structure and pore size of porous fibers, a method utilizing phase separation between the amorphous 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 amorphous polymer and the desired pore size range.

[0061] 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.

[0062] The method for producing porous fibers obtained by solution spinning will be described below.

[0063] The porous fiber of the present invention comprises a "stock solution production step of dissolving an amorphous polymer in a solvent to obtain a spinning dope", followed by a "discharge step of heating the spinning dope to above its gel point and discharging it from a spinneret", followed by a "cooling step of cooling the spinning dope to below its gel point 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 amorphous 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 its gel point. -1 The following scattering can be obtained by the manufacturing method.

[0064] The "process for producing a spinning dope by dissolving an amorphous polymer in a solvent" refers to a process for obtaining a spinning dope by dissolving a solid amorphous polymer in a solvent. The dissolving method is not particularly limited, but a method in which the amorphous 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.

[0065] 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 process 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.

[0066] 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.

[0067] The "coagulation process for forming porous fibers in a coagulation bath containing a compound that is incompatible with the amorphous polymer in the spinning dope" refers to a process in which the spinning dope (a precursor of porous solid fibers containing a solvent) that has undergone the above-mentioned discharge and cooling processes is introduced into a coagulation bath, where a material exchange occurs between the solvent used in the dope production process and the compound that is incompatible with the amorphous polymer contained in the coagulation bath, causing the amorphous polymer to precipitate, thereby forming porous fibers.

[0068] In the spinning dope of the present invention, the porous structure of the fiber cross section and the outer surface of the obtained porous fiber can be influenced by controlling the nanodomain structure in the spinning dope that is derived from phase separation and gelation.

[0069] 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 In ultra-small angle X-ray scattering measurements, the scattering vector (q) is 1 nm. -1The presence of scattering below this level means that nano-domain structures of several nanometers or more have been formed in the spinning dope. That is, the nano-domain structures have already been formed in the spinning dope during the extrusion process from the spinneret heated to the gel point or higher, and the nano-domain structures grow and become fixed through the cooling and solidification processes, thereby determining the pore structure of the porous fiber.

[0070] 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 amorphous 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.

[0071] 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.

[0072] The spinning dope of the present invention may be composed only of an amorphous polymer and a good solvent, but preferably contains a poor solvent for the amorphous polymer in addition to the amorphous polymer and good solvent. Here, a good solvent is a solvent that can dissolve the amorphous polymer uniformly, and a poor solvent is a solvent that does not dissolve the amorphous polymer uniformly even when heated to a high temperature. This is because, rather than achieving a homogeneous state in which the amorphous polymer and the good solvent are completely compatible with each other, the addition of a poor solvent adjusts the affinity of the amorphous polymer for the solvent and controls phase separation, i.e., controls the formation and growth of nanodomain structures.

[0073] Examples of amorphous polymer materials used in the raw material solution production process include PMMA, PAN, polyacrylamide, polysulfone, polyethersulfone, polyarylethersulfone, polystyrene, polycarbonate, and derivatives thereof. Among these, PMMA, PAN, polysulfone, polyethersulfone, and polystyrene, which have appropriate hydrophobic interactions, are preferably used, and PMMA is particularly preferably used.

[0074] The solvent used in the raw solution production step includes a good solvent for the amorphous polymer. Although one type of good solvent or a mixture of multiple types can be used, it is preferable to use only one type from the viewpoints of cost and resource recovery.

[0075] 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, ester compounds such as ethyl acetate and butyl acetate, halogen-containing compounds such as chloroform, dichloromethane, and chlorobenzene, 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.

[0076] The type of poor solvent is not particularly limited, but when the organic polymer is PMMA, preferred poor solvents include water, alcohol compounds such as methanol, ethanol, n-propanol, iso-propanol, 1-butanol, ethylene glycol, propylene glycol, diethylene glycol, 1,3-propanediol, 1,4-butanediol, 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.

[0077] Furthermore, in the relationship between an amorphous polymer and a poor solvent, it is important that there be interactions such as hydrophobic interactions, electrostatic interactions, and hydrogen bonds for the purposes of controlling the formation of nano-domain structures, promoting the formation of microcrystals of the amorphous polymer, and improving spinnability. Although a combination of these principles may be used, hydrogen bonds are more preferred because the strength of the interactions is appropriate.

[0078] Specifically, it is preferable that the amorphous polymer is a polymer containing a hydrogen bond donor functional group and the poor solvent is a hydrogen bond acceptor compound, or that the amorphous polymer is a polymer containing a hydrogen bond acceptor functional group and the poor solvent is a hydrogen bond donor compound. By forming a hydrogen bond between the amorphous polymer and the poor solvent, the orientation of the hydrogen bond-forming functional group present in the amorphous polymer, i.e., the hydrogen bond donor or acceptor functional group, can be controlled, thereby controlling the higher-order structure of the amorphous polymer.

[0079] This is thought to promote the formation of amorphous polymer microcrystals, thereby increasing the mechanical strength of the porous fiber and improving spinnability. Furthermore, the formation of interactions with the poor solvent allows for the appropriate control of the mobility of the amorphous polymer, thereby controlling the formation and growth of nanodomain structures.

[0080] From these points of view, the poor solvent is preferably a compound containing a hydrogen bond donor or acceptor functional group.

[0081] Specific compounds containing a hydrogen bond donor functional group are not particularly limited, but are preferably water or compounds having a hydroxyl group or an amino group, and more preferably water, ethylene glycol, propylene glycol, 1,4-butanediol, glycerin, or formamide.

[0082] 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.

[0083] 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 type of amorphous polymer, good solvent, and poor solvent, as the interaction and motility vary. For example, when PMMA is used as the amorphous 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.

[0084] The weight ratio of the amorphous 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 resulting porous fiber by promoting physical and chemical crosslinking, such as entanglement and gelation of the amorphous polymers, the weight ratio of the amorphous 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 resulting porous fiber, the weight ratio is preferably 20% by weight or less, more preferably 18% by weight or less, and even more preferably 15% by weight or less.

[0085] 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 amorphous polymers, the weight-average molecular weight of the amorphous 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.

[0086] 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 amorphous 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.

[0087] The temperature in the extrusion 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 extruding it from the spinneret, the temperature in the extrusion step is preferably heated to or above the gel point of the spinning dope. For example, in the case of a spinning dope containing PMMA and DMSO, the temperature in the extrusion 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, to avoid decomposition of the components of the spinning dope, the temperature in the extrusion step is preferably 150°C or lower, more preferably 130°C or lower, and even more preferably 110°C or lower.

[0088] 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.

[0089] In the coagulation step, the spinning dope (a precursor of the porous solid fiber containing a solvent) that has been cooled undergoes solvent exchange with a compound that is incompatible with the amorphous polymer contained in the coagulation bath, resulting in the precipitation of the amorphous polymer, thereby obtaining a porous fiber. The compound that is incompatible with the amorphous polymer is not particularly limited, but examples thereof include water and alcohol compounds.

[0090] 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 less, more preferably 90° C. or less, and even more preferably 80° C. or less. On the other hand, in order to promote solvent exchange, the temperature of the coagulation bath is preferably 10° C. or more, more preferably 20° C. or more, and even more preferably 30° C. or more.

[0091] 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.

[0092] 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.

[0093] The present invention relates to an adsorption column in which the fiber bundle of the present invention is incorporated into a casing having ports at both ends that communicate with the interior. The shape of the casing can be, for example, a rectangular or hexagonal tubular or cylindrical body with both ends open.

[0094] Among these, a cylindrical body, especially one with a perfectly circular cross section in the radial direction, is preferred. 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.

[0095] 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.

[0096] When plastic is used as the casing material, 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.

[0097] 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, for example, because the internal state can be observed during perfusion of the liquid to be treated.

[0098] 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.

[0099] 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.

[0100] 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.

[0101] 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.

[0102] 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.

[0103] 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.

[0104] 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. [Example]

[0105] 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. (Method for determining peaks derived from microcrystals) The porous fiber was fixed to an automatic sample changer at BL03XU, No. 2 Hutch, SPring-8, and irradiated perpendicularly to the fiber axis with X-rays with a beam diameter of approximately 100 μm and a wavelength of 0.1 nm. 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, WaveMetrics) with the horizontal axis representing the scattering vector q and the vertical axis representing the X-ray scattering intensity.

[0106] The camera length is approximately 50 to 90 mm, and can be arbitrarily determined within a range that allows for observation of scattering from the target microcrystals. After one-dimensionalization, appropriate background subtraction was performed to ensure that only scattering from the porous fiber was observed. Specifically, if there was nothing in the optical path other than the porous fiber, background was subtracted by air scattering; if the porous fiber was placed in a cell made of water or film to prevent drying, background was subtracted by scattering from the empty cell.

[0107] Furthermore, if the porous fiber contains a third component, such as fine particles other than amorphous polymers, the scattering from the third component is also subjected to appropriate background subtraction. The peaks in the scattering spectrum from which the background has been subtracted are assigned using literature and X-ray structural analysis, and if even one peak is assigned to a microcrystal, it is determined that microcrystals are present.

[0108] For example, the scattering vector of the amorphous peak of PMMA is q = 0.95 Å -1 In the case of PMMA stereocomplex crystallites, the stereocomplex peaks are q = 0.29, 0.84, and 1.14 Å. -1 It is known that there is a peak in (Macromolecules, 2021, 54, 2001-2010).

[0109] Therefore, q = 0.29, 0.84, 1.14 Å -1 Near (±0.05Å -1 If there is at least one peak within the error range of 101, it is determined that microcrystals are present. Also, as shown in Figure 1, if a peak derived from microcrystals overlaps with a peak derived from amorphous crystals 101, forming a shoulder peak 100, it is determined that microcrystals are present. 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.

[0110] For example, for PMMA stereocomplex crystallites, q = 0.95 Å -1 The residuals after fitting with the peak position as q = 0.29, 0.84, 1.14 Å -1 If at least one peak remains in the vicinity (is convex upward), it is determined that stereocomplex crystallites are present.

[0111] Conversely, if the residuals after fitting the amorphous peaks do not show any peaks at the positions of the microcrystalline peaks (they are not convex upwards), it is determined that no microcrystalline exists. For example, for PMMA stereocomplex microcrystals, q = 0.95 Å -1 The residuals after fitting with the peak position as q = 0.29, 0.84, 1.14 Å -1 When no peak remained at any position in the vicinity (no upward convexity), it was determined that no microcrystals were present.

[0112] 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=0.84Å -1 The peak position is determined by fitting the peak position to the peak of the other microcrystals (e.g., q = 1.14 Å). -1 ) and amorphous origin q=0.95Å -1When there were other peaks nearby, forming shoulder peaks, the exact peak position of the peak derived from the microcrystals was determined by peak separation using fitting for 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.

[0113] The peak position is q = ±0.05 Å. -1 If a peak was found within the error range, it was determined to be the peak in question.

[0114] (average pore size near the outer surface of the fiber cross section) The porous fiber was then placed in a water-filled container and frozen in liquid nitrogen to obtain a block with the porous fiber embedded in it. The block was then sliced ​​at −65°C and 200 nm thick using an ultramicrotome equipped with a cryosystem to obtain sections exposing the radial cross-section of the porous fiber.

[0115] 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.

[0116] The fiber cross section of the sample was observed under a scanning electron microscope (S-5500 manufactured by Hitachi High-Technologies Corporation), and when an arbitrary 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) that allowed sufficient observation of the pores, excluding the small dense layer region present on the outermost surface.

[0117] After imaging, the image was binarized using image analysis software (ImageJ) so that the pores were black and the structure was white, and the total area of ​​the pores was calculated. If it was difficult to binarize the pore and structure parts 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 similar. Then, the transparent sheet was copied onto white paper, and the image was binarized so that the pores were black and the structure was white.

[0118] Black areas with five or fewer consecutive pixels were treated as white areas, which are structures, because it was impossible to distinguish between noise and pores. The equivalent circle diameter, which is the diameter of a circle with the same area, was calculated from the area of ​​each pore, and the resulting equivalent circle diameters were sorted in descending order. The areas of the pores were added up, starting with the pore with the largest 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.

[0119] The cross-sectional pore diameters were calculated in the same manner at three random locations within the region near the outer surface, and the average was taken as the average pore diameter near the outer surface of the fiber cross section. The average pore diameter was rounded to one decimal place.

[0120] (average pore size near the center of the fiber cross section) The same procedure was performed as in the above-mentioned "average pore diameter near the outer surface of the fiber cross section," 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.

[0121] (average pore size in the middle region of the fiber cross section) The same procedure was performed as in the above-mentioned "average pore diameter near the outer surface of the fiber cross section," except that the region observed and photographed was the middle region of the porous fiber, and the average pore diameter in the middle region of the fiber cross section was calculated.

[0122] (average pore size of fiber cross section) A 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 average pore diameters of the small regions are designated R1 to R2 in order of proximity to the center point. 10 , the area of ​​each small region is S1 to S10 When this is the case, the average pore size of the fiber cross section is expressed by the following formula (1).

[0123]

number

[0124] The average pore size Rj of each small region is calculated in the same manner as in the above-mentioned "average pore size near the outer surface of the fiber cross section," except that the region to be observed and photographed is each small region.

[0125] (Opening rate of outer surface of fiber) The porous fiber was thoroughly wetted and frozen in liquid nitrogen, then freeze-dried in a vacuum dryer at 0.1 torr or less for 24 hours to sublimate the water, yielding a dried sample. A thin film of platinum-palladium (Pt-Pd) was then formed on the sample surface by sputtering, providing a surface observation sample.

[0126] The fiber surface of the surface observation sample was observed using a scanning electron microscope (S-5500, manufactured by Hitachi High-Technologies Corporation), and images were taken at any position on the fiber surface. The magnification was set to 5,000 to 10,000 times, so that pores could be clearly seen. After capturing the images, the pores contained in each image were measured, and the total area of ​​all pores was calculated. If no pores were observed in five images spaced at least 1 cm apart in the longitudinal direction of the fiber at 10,000 times magnification, it was determined that there were no pores on the outer surface of the fiber.

[0127] The total area of ​​all pores was calculated by binarizing the electron microscope image using the image analysis software "ImageJ" so that pores were black and non-pores were white. The resulting image was analyzed to calculate the total area of ​​all pores. When it was difficult to binarize the pore and non-pore areas due to contrast differences in the electron microscope image, a transparent sheet was placed over the printout and the pores were filled in black using a black pen or similar. The transparent sheet was then copied onto white paper, and the image was binarized so that pores were black and non-pores were white, and then analyzed.

[0128] The porosity 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 at least 1 cm apart in the longitudinal direction of the fiber, and the values ​​were averaged and rounded to one decimal place.

[0129] 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 size on the outer surface of the fiber) Using the binarized image obtained in the above-mentioned "Opening ratio of the outer surface of the fiber," the equivalent circle diameter was calculated from the area of ​​each pore. The equivalent circle diameters were then arranged in descending order, and the areas of the pores were added up, starting with the pore with the largest equivalent circle diameter. When the sum exceeded half of the total area of ​​all the pores, the equivalent circle diameter of the pore was defined as the surface pore diameter.

[0130] The equivalent circle diameters were calculated in the same manner using nine or more images spaced at least 1 cm apart in the longitudinal direction of the fiber, and the average was used as the average pore diameter on the outer surface of the fiber. Note that the average pore diameter on the outer surface of the fiber was rounded to one decimal place.

[0131] (Aspect ratio of the long and short diameters of the pores on the outer surface of the fiber) Using the binarized images obtained in the "Opening ratio of the outer surface of the fiber" section above, 15 or more pores per image were fitted with ellipses to calculate the ratio of their major axis to their minor axis. Similar measurements were performed on nine or more images spaced at intervals of 1 cm or more along the fiber length, and the values ​​were averaged to calculate the aspect ratio of the major axis to the minor axis of the pores on the outer surface of the fiber.

[0132] (Viscosity of spinning dope) Viscosity is measured in a constant temperature bath set at a high temperature using the falling ball method in accordance with JIS Z 8803 (2011 edition). Specifically, a viscosity tube with an inner diameter of 40 mm is filled with the spinning solution, a steel ball (made of SUS316) with a diameter of 2 mm is dropped into the solution, and the time required for the steel ball to fall 200 mm is measured. The temperature during measurement is 110°C.

[0133] (Gel point of spinning dope) The gel point of the spinning dope was determined as the temperature at which the viscosity suddenly increased while the viscosity measurement temperature was lowered in 5°C intervals from 110°C in the above "Viscosity of the spinning dope." Specifically, the gel point was determined as the temperature at which the viscosity reached 10 times or more the viscosity at 110°C.

[0134] (Ultra-small angle X-ray scattering of spinning dope) A through-hole was drilled in a 0.5 mm thick silicone rubber sheet, and the spinning dope was sealed in a measurement cell covered on both sides with Kapton film. The measurement cell containing the spinning dope was fixed to a cooling and heating stage (Linkam Co., Ltd.) in the second hatch of SPring-8, BL03XU.

[0135] After heating the measurement cell to 110°C, the temperature was decreased at a rate of 5°C / min, and 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.

[0136] The ultra-small angle X-ray scattering image obtained with the PILATUS detector was converted into one dimension using the 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.

[0137] For a reference sample in which only the solvent of the spinning solution was enclosed in the measurement cell, ultra-small angle X-ray scattering was measured under the same conditions, and background processing was performed. The scattering spectrum after background processing was measured at q = 1 nm -1 In the following region, X-ray scattering was determined to be observed if there was a region where the scattering intensity increased as q decreased, as shown in Figure 2.

[0138] (Spinnability) The judgment was as follows: ◯: When the porous fiber was wound at a spinning speed of 5 m / min, 150 m could be wound without thread breakage. △: When 150 m of porous fiber was wound at a spinning speed of 5 m / min, the fiber broke 1 to 3 times. ×: When 150 m of porous fiber was wound at a spinning speed of 5 m / min, the fiber broke four or more times.

[0139] (dispersion component of surface free energy) The freeze-dried porous fiber was packed into a glass column, and the dispersive component of the surface free energy was measured and calculated using a surface free energy analyzer (iGC-SEA) manufactured by Japan Science Core Co., Ltd., following the method described in "Inverse gas chromatography applications: A review" Adv. Colloid Interface Sci., 212, 21-44 (2014). Specifically, linear alkanes with 6 to 9 carbon atoms were used as the test solvent, and the retention volume was calculated from the resulting chromatogram. The dispersive component of the surface free energy was calculated from the retention volume of each alkane. (Adsorption performance of porous fibers) The porous fiber is 0.01 to 0.10 g / mm 2 The porous fiber was fixed under tension and cut to obtain a section exposing the radial cross section of the porous fiber. The cut surface was magnified and photographed with an optical microscope, and the perimeter P (cm) was calculated by tracing the outer periphery of the fiber cross section using image analysis software.

[0140] Two hundred porous fibers were cut into 5.5 cm lengths in the longitudinal direction of the fiber and then chopped into small pieces to prepare samples for the adsorption test. The total surface area S (cm 2 ) was calculated using the following formula (3-1):

[0141] S(cm 2 )=P(cm)×5.5(cm)×200...Equation (3-1) The 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. Using a seesaw shaker (TAITEC Wave-SI) set to 38 and the maximum angle (one cycle per 1.7 seconds), the sample was shaken and stirred at 37°C for 4 hours. 1 mL of human plasma was sampled before contact with the porous fiber and after stirring.

[0142] LDL cholesterol was measured by the direct method. 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 amount of adsorption per fiber surface area was calculated using the following formula (3-2).

[0143] 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.

[0144] [Example 1] The spinning solution was prepared by mixing 200 parts by weight of syn-PMMA (weight-average molecular weight: 1.4 million), 40 parts by weight of iso-PMMA (weight-average molecular weight: 500,000), 1560 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 resulting spinning solution was 90°C, and the viscosity at 110°C was 175.5 Pa·s.

[0145] 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, 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% 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 1.

[0146] [Example 2] The spinning solution was prepared by mixing 200 parts by weight of syn-PMMA (weight-average molecular weight: 1.4 million), 40 parts by weight of iso-PMMA (weight-average molecular weight: 500,000), 1627 parts by weight of DMSO, and 88 parts by weight of 1,4-butanediol to achieve a PMMA concentration of 12% by weight. The resulting spinning solution had a gel point of 75°C and a viscosity of 201.0 Pa·s at 110°C.

[0147] The spinning dope was discharged into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The speed of the cold air during free-running was 30 m / s. 3 The fiber was cooled at 100°C / 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% 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 2.

[0148] [Example 3] The spinning solution was prepared by mixing 200 parts by weight of syn-PMMA (weight-average molecular weight: 1.4 million), 40 parts by weight of iso-PMMA (weight-average molecular weight: 500,000), 1627 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 resulting spinning solution was 75°C, and the viscosity at 110°C was 242.0 Pa·s.

[0149] The spinning dope was discharged into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The speed of the cold air during free-running was 30 m / s. 3 The fiber was cooled at 100°C / 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% 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 3.

[0150] [Example 4] The spinning solution was prepared by mixing 117 parts by weight of syn-PMMA (weight-average molecular weight: 1.4 million), 23 parts by weight of iso-PMMA (weight-average molecular weight: 500,000), 1,418 parts by weight of DMSO, and 43 parts by weight of water to a PMMA concentration of 8.8% by weight, and stirring at 110°C for 8 hours. The gel point of the resulting spinning solution was 60°C, and the viscosity at 110°C was 63.7 Pa·s.

[0151] The spinning dope was discharged into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The speed of the cold air during free-running was 30 m / s. 3 The fiber was cooled at 100°C / 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% 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.

[0152] [Example 5] The spinning solution was prepared by mixing 200 parts by weight of syn-PMMA (weight-average molecular weight: 1.4 million), 40 parts by weight of iso-PMMA (weight-average molecular weight: 500,000), 1627 parts by weight of DMSO, and 88 parts by weight of glycerin to a PMMA concentration of 12% by weight, and stirring at 110°C for 8 hours. The gel point of the resulting spinning solution was 75°C, and the viscosity at 110°C was 230.0 Pa s.

[0153] 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 50cm. The cold air velocity during free-running was 36m / s. 3 The fiber was cooled at 100°C / 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% 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 5.

[0154] [Example 6] The spinning solution was prepared by mixing 178 parts by weight of syn-PMMA (weight-average molecular weight: 1.4 million), 36 parts by weight of iso-PMMA (weight-average molecular weight: 0.5 million), 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 resulting spinning solution was 60°C, and the viscosity at 110°C was 25.9 Pa·s.

[0155] 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, 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% 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 3 m / min to obtain porous fiber 6.

[0156] [Example 7] The spinning solution was prepared by mixing 287 parts by weight of syn-PMMA (weight-average molecular weight: 1.4 million), 57 parts by weight of iso-PMMA (weight-average molecular weight: 0.5 million), 2947 parts by weight of DMSO, and 155 parts by weight of glycerin, so that the PMMA concentration was 10% by weight. The gel point of the resulting spinning solution was 65°C, and the viscosity at 110°C was 30.3 Pa·s.

[0157] The spinning dope was discharged into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The speed of the cold air during free-running was 30 m / s. 3 The fiber was cooled at 100°C / h. Thereafter, it was introduced into a coagulation bath consisting of water at 72°C. The obtained porous fiber was washed with water in a 40°C water bath, 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 7.

[0158] [Example 8] The same procedure as in Example 5 was carried out except that the cold air flow rate was 24 m3 / h and the coagulation bath temperature was 75°C, to obtain porous fiber 8.

[0159] [Comparative Example 1] The spinning solution was prepared by mixing 290 parts by weight of syn-PMMA (weight-average molecular weight: 1.4 million), 58 parts by weight of iso-PMMA (weight-average molecular weight: 0.5 million), and 2554 parts by weight of DMSO, so that the PMMA concentration was 12% by weight. The gel point of the resulting spinning solution was 65°C, and the viscosity at 110°C was 154.6 Pa·s.

[0160] The spinning dope was discharged into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The speed of the cold air during free-running was 30 m / s. 3 The fiber was cooled at 100°C / 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% 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 9.

[0161] Comparative Example 2 The spinning solution was prepared by mixing 167 parts by weight of syn-PMMA (weight-average molecular weight: 1.4 million), 33 parts by weight of iso-PMMA (weight-average molecular weight: 500,000), and 1,800 parts by weight of DMSO, so that the PMMA concentration was 10% by weight. The gel point of the resulting spinning solution was 60°C, and the viscosity at 110°C was 24.0 Pa·s.

[0162] The spinning dope was discharged into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The speed of the cold air 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 72°C. The obtained porous fiber was washed with water in a 40°C water bath, 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 10.

[0163] Comparative Example 3 The spinning solution was prepared by mixing 200 parts by weight of syn-PMMA (weight-average molecular weight: 1.4 million), 40 parts by weight of iso-PMMA (weight-average molecular weight: 500,000), 1627 parts by weight of DMSO, and 88 parts by weight of N-methyl-2-pyrrolidone, so that the PMMA concentration was 12% by weight. The gel point of the resulting spinning solution was 65°C, and the viscosity at 110°C was 121.9 Pa·s.

[0164] The spinning dope was discharged into the air using a circular nozzle. The nozzle temperature was 95°C. The length of the free-running section was 50 cm. The speed of the cold air 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 to keep it moist. After passing through a heat treatment bath at 85°C to remove excess glycerin, the fiber was taken up at 20 m / min to obtain porous fiber 11.

[0165] Comparative Example 4 The length of the free-running section is 0.3 cm, and the amount of cold air is 0 m. 3 The same procedure as in Example 5 was carried out except that the heating time was changed to / h, and porous fiber 12 was obtained.

[0166] The spinning conditions obtained in Examples 1 to 8 are shown in Table 1, and the spinning conditions obtained in Comparative Examples 1 to 4 are shown in Table 2. The evaluation results of Examples 1 to 8 are shown in Table 3, and the evaluation results of Comparative Examples 1 to 4 are shown in Table 4.

[0167] [Table 1]

[0168] [Table 2]

[0169] [Table 3]

[0170] [Table 4] [Industrial Applicability]

[0171] 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, an adsorbent, a heat insulator, a sound absorber, an impact buffer, a substrate for cell culture, a carrier for regenerative medicine, etc. In particular, in medical applications, it is suitably used for removing pathogenic proteins and the like from blood, plasma, and body fluids. [Explanation of symbols]

[0172] 100: Shoulder peak due to microcrystals, 101: Peak due to amorphous

Claims

1. Contains an amorphous polymer, The average pore size of the fiber cross section is 100 to 1000 nm; The peak of the scattering vector (q) derived from the microcrystals of the amorphous polymer obtained by wide-angle X-ray scattering measurement is in the range of 0.2<q<1.2Å. －１ Porous fibers present in

2. The peaks of the scattering vectors originating from the microcrystals of the amorphous polymer are q=0.29, 0.84, and 1.14 Å. －１ 2. The porous fiber according to claim 1, wherein the porous fiber is present in any one of the following:

3. 3. The porous fiber according to claim 1, wherein the amorphous polymer contains a syndiotactic isomer and an isotactic isomer, and the peak of the scattering vector (q) is derived from a stereocomplex structure obtained by mixing the syndiotactic isomer and the isotactic isomer.

4. The porous fiber according to any one of claims 1 to 3, wherein the amorphous polymer is polymethyl methacrylate.

5. The porous fiber according to any one of claims 1 to 4, wherein the porous fiber is a solid fiber.

6. A fiber bundle comprising the porous fiber according to any one of claims 1 to 5.

7. A liquid treatment column comprising the fiber bundle of claim 6.

8. a dope production step of dissolving an amorphous polymer in a solvent to obtain a spinning dope; a discharge step of heating the spinning dope to a gel point or higher and discharging it from a spinneret; a cooling step of cooling the spinning dope to a gel point or lower in a dry section after being discharged from a spinneret, 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 A method for producing porous fibers having scattering below.

9. The method for producing a porous fiber according to claim 8 , wherein the solvent includes a good solvent and a poor solvent for the amorphous polymer.

10. 10. The method for producing a porous fiber according to claim 9, wherein the amorphous polymer is a polymer containing a functional group with hydrogen bond donor properties, and the poor solvent is a compound with hydrogen bond acceptor properties.

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