Nonwoven fabric substrate, liquid purification fiber material, method for manufacturing the material, and washing device equipped with the material

Abstract

[Problem] To provide a fibrous material for liquid clarification, which is inexpensive and with which it is possible to reduce cleaning and suppress the occurrence of fine particles, and to provide a cleaner equipped with the same.　[Solution] The present invention relates to: a nonwoven substrate that is used in a fibrous material for liquid clarification in order to remove biologically harmful substances from a liquid, and that includes a mixed resin composed of a polyolefin and a styrene-olefin copolymer within each fiber, wherein the ratio of the polyolefin mass to the mixed resin mass is 10 mass% to 80 mass% inclusive, and the ratio of the total styrene residue mass to the styrene-olefin copolymer mass is 5 mass% to 50 mass% inclusive; a fibrous material for liquid clarification using said nonwoven substrate; a production method for said material; and a cleaner equipped with said material.

Description

Cross-reference

[0001] This application claims priority based on Japanese Patent Application No. 2021-123959 filed in Japan on July 29, 2021, and the contents described in said application are incorporated herein by reference. In addition, the contents described in the patents, patent applications and documents cited in the present application are incorporated herein by reference. [Technical Field]

[0002] The present invention relates to a nonwoven fabric substrate, a fiber material for liquid purification using the nonwoven fabric substrate, a method for producing the fiber material for liquid purification, and a cleaner comprising the fiber material for liquid purification. [Background Art]

[0003] For processes of removing and purifying contaminants such as medical devices and drug solutions, and for reducing biological reactions caused by biological infections and biohazardous substances produced thereby, so-called column adsorption devices have been developed, in which a target liquid is refluxed in a device equipped with an adsorption carrier to remove causative substances, and have achieved great results both industrially and clinically. However, including the recent outbreak of COVID-19 infection, and the problems of diffusion and pollution of viruses and biohazardous substances into the environment, the development of new high-functional carriers for purification is desired. For example, in the medical field, apheresis therapy is performed for the prevention and treatment of various immune diseases, sepsis, etc., and the development of adsorption-type blood purifiers incorporating an adsorption carrier with high blood compatibility and high causative substance selectivity is in progress.

[0004] As an example of an adsorbent used in apheresis, Patent Document 1 (JP 2019-136499) discloses an adsorbent as a material for removing activated leukocyte-platelet complexes contained in blood, comprising a water-insoluble carrier containing a ligand and a substrate, wherein the ligand has a structure in which a hydrocarbon group bonded to a carbon atom of a secondary amide is bonded, and the ligand may be substituted with substituents selected from the group consisting of halogen atoms, hydroxyl groups, ketone groups, ether groups, and ester groups. Here, "ligand" refers to a chemical substance or chemical structure that imparts adsorption performance, and "substrate" refers to a material capable of interacting with the ligand.

[0005] Furthermore, Patent Document 2 (WO2019 / 049961 A1) discloses an immunosuppressive protein adsorption material and an adsorption column, which uses a polymer alloy (mixture) of polystyrene and polypropylene to which one or more nitrogen-containing compounds consisting of a polyamine represented by a predetermined formula and an aliphatic amine represented by a predetermined formula are bonded. More specifically, this carrier is a knitted fabric of a sea-island structure fibrous body in which multiple fibers made of polypropylene are surrounded by a polymer alloy of polystyrene and polypropylene, and it is said that physical strength is maintained due to this structure. In fact, in the examples, the number of fine particles in the column was measured after vibrating the column horizontally and vertically for one hour in accordance with the vibration test method for packaged goods and containers (JIS Z 0232), and it was shown that the number was small enough to be used for medical purposes.

[0006] Furthermore, numerous studies have been conducted on knitted fabrics of polymer alloy fibers having the aforementioned sea-island structure, as shown in Patent Document 3-10. For example, Patent Documents 3 (JP-P5-71603) and 4 (JP-A-1-279908) describe its application as a bilirubin adsorbent, Patent Document 5 (JP-A-11-104236) describes the adsorption properties of activated macrophages by sea-island structure fibers immobilized with polymyxin B, Patent Document 6 (JP-P6-22623) describes an endotoxin adsorbent with low heparin adsorption capacity, Patent Documents 7 (JP-A-60-5166) and 8 (JP-A-5-329207) describe the endotoxin removal performance of sea-island structure fibers immobilized with polymyxin, Patent Document 9 (JP-A-60-209525) describes the decomposition properties of endotoxins, and Patent Document 10 (Patent No. 3817808) describes the ability to adsorb enterotoxins in addition to endotoxins, demonstrating the wide range of applications of the fiber as a carrier for adsorbents.

[0007] Furthermore, the polymer material that constitutes this sea-island structure fiber is described in detail, for example, in Patent Document 1, as follows. (The following is a quote): "The material for removing activated leukocyte-activated platelet complexes comprises a water-insoluble carrier containing a ligand and a substrate, and the ligand is..." "As the substrate, for example, a polymer material that repeatedly contains functional groups that have reactivity with carbon cations, such as aromatic rings and hydroxyl groups, in its structure, and may be synthetic polymer materials such as poly(aromatic vinyl compounds) (e.g., polystyrene), polyester (e.g., polyethylene terephthalate, polybutylene terephthalate), polysulfone, polyethersulfone, polyvinyl alcohol, or natural polymer materials such as cellulose, collagen, chitin, chitosan, dextran, or derivatives of the above synthetic polymer materials or above natural polymer materials to which alkyl groups, halogen atoms, halogenated alkyl groups, acetal groups, ether groups, etc. may be attached, for example, if it is a polystyrene derivative, it may be poly-p-chloromethylstyrene, poly-α-methylstyrene, poly-β-methylstyrene, poly-p-tert-butoxystyrene, poly-p-acetoxy Examples include cystyrene and poly-p-(1-ethoxy)styrene. There are no particular restrictions on the composition of these polymer materials; homopolymers, copolymers using multiple types of monomers of the above polymer materials, or physical blends of multiple above polymer materials may be used. In particular, for the material used to remove activated leukocyte-activated platelet complexes, poly(aromatic vinyl compounds) (e.g., polystyrene) or its derivatives, polyester (e.g., polyethylene terephthalate, polybutylene terephthalate) or its derivatives, polysulfone or its derivatives, or polyethersulfone or its derivatives are preferred, and polystyrene or polysulfone or their derivatives, i.e., polystyrene or its derivatives or polysulfone or its derivatives are more preferred. Among these, polystyrene or its derivatives are even more preferred because they have a large number of aromatic rings per unit weight and ligands can be easily introduced. The material used as the base material may also contain a crosslinked structure.While there are no restrictions on the crosslinking structure, materials in which a crosslinking structure is introduced by copolymerizing a difunctional monomer such as divinylbenzene, or materials in which a crosslinking structure is introduced by reacting a crosslinking agent such as an aldehyde with functional groups such as aromatic rings and hydroxyl groups in the material are preferred. Materials in which a crosslinking structure is introduced by reacting a difunctional compound with functional groups such as aromatic rings and hydroxyl groups in the material are more preferred due to their ease of procurement, and it is even more preferable to use formaldehyde as the crosslinking agent. (End of quote)

[0008] Furthermore, Patent Document 11 (JP 2003-511354) discloses an endotoxin adsorbent in which polydispersible oligopeptides are immobilized on porous beads such as Toyo Pearl HW70EC; Patent Document 12 (JP 2012-515577) discloses an endotoxin adsorbent in which porous particles made of polystyrene-divinylbenzene copolymer with a particle size of about 5 μm are hydrophobically coated with polymyxin; Patent Document 13 (JP 4-270965) discloses an LPS (endotoxin) adsorption carrier in which oligopeptides such as polymyxin B are hydrophobically bound to the surface of a film or sheet of polystyrene or other materials, or a cloth (woven or nonwoven) of polyester or polypropylene; and Patent Document 14 (JP 2016-137099) discloses a blood purifier in the form of a flexible container equipped with an aggregate of porous solid threads mainly composed of cellulose, polymethyl methacrylate, etc., aligned in one direction.

[0009] In addition, Patent Document 15 (Patent No. 3533541) states that nonwoven fabrics made of synthetic polymer compounds such as polystyrene, polyalkylstyrene, polyethylene, polypropylene, polyethylene terephthalate, polymethyl methacrylate, and polysulfone, copolymers of monomers of these compounds, block polymers, and blends or alloys of these polymer compounds can be used as cell selection filters. It also states that, in terms of mechanical strength and surface area, the fiber diameter of the effective filter should be between 1 μm and 100 μm. [Prior art documents] [Patent Documents]

[0010] [Patent Document 1] Japanese Patent Publication No. 2019-136499 [Patent Document 2] WO2019 / 049961A1 [Patent Document 3] Tokuhei 5-71603 [Patent Document 4] Japanese Patent Publication No. 1-279908 [Patent Document 5] Japanese Patent Publication No. 11-104236 [Patent Document 6] Tokuhei 6-22623 [Patent Document 7] Japanese Patent Publication No. 60-5166 [Patent Document 8] Japanese Patent Publication No. 5-329207 [Patent Document 9] Japanese Patent Publication No. 60-209525 [Patent Document 10] Patent No. 3817808 [Patent Document 11] Special Publication 2003-511354 [Patent Document 12] Special Publication 2012-515577 [Patent Document 13] Japanese Patent Publication No. 4-270965 [Patent Document 14] Japanese Patent Publication No. 2016-137099 [Patent Document 15] Patent No. 3533541 [Overview of the project] [Problems that the invention aims to solve]

[0011] However, the above-mentioned known adsorbents have problems that need to be addressed.

[0012] Patent Document 1 investigates the desorption of ligands by pH change when immersed in 50°C water for 24 hours, but it does not mention the pH when autoclaving (121°C, 20 minutes), which is important in practical applications. Although Patent Document 2 evaluates durability against vibration during transportation, it does not disclose anything regarding the strength and fragility of the carrier itself, which pose problems in actual manufacturing processes and reaction steps. Patent Documents 3 to 10 disclose various adsorbers using sea-island structure fibers. Regarding the polymer material used as the material for the fibers, (1) "There are no particular restrictions on the composition of these polymer materials, and homopolymers, copolymers obtained by using multiple types of monomers of the above polymer materials, or a plurality of the above polymer materials physically blended may be used" (2) Among these, polystyrene or derivatives thereof are more preferable because they have a large number of aromatic rings per unit weight and allow easy introduction of ligands. (3) A crosslinked structure may be included. These contents are disclosed in the above documents.

[0013] However, there is no idea of selection focusing on the fragility of the fibers themselves, for example, the generation of fine particles that causes problems depending on manufacturing processes, transportation processes, and usage conditions. If anything, it can be said that the approach is to increase strength through crosslinking. In addition, the reason why polystyrene or a derivative thereof is selected as the optimal material is the number of aromatic rings per unit weight, and the underlying idea is based on the large introduction amount of ligands. That is, importance is placed on materials having a structure that allows introduction of as many ligands as possible, and there is no explicit example of limiting the aromatic ring content of the material itself to improve the fragility of the fiber material, for example. Furthermore, sea-island structure fibers require special manufacturing equipment to realize their elaborate structure, and thus have the practical problem of high manufacturing cost.

[0014] In Patent Documents 11 to 14, beads, films, non-woven fabrics, solid threads and the like are disclosed as shapes of base materials or carriers, and various polymer materials are listed as base materials. However, specific studies have not been conducted on the strength, brittleness, sterilization resistance and the like of the base material itself. Although it is described in Example 15 that various polymer materials, copolymers and block copolymers can be used as the base material, only "non-woven fabric made of polystyrene" is used in the examples, and there is no concept of material selection considering, for example, test results regarding fiber brittleness (generation of fine particles) or steam sterilization resistance.

[0015] As described above, research and development of conventional adsorbents have been promoted with emphasis on adsorption performance, particularly selectivity. There remains room for improvement in the processability of the base material itself in manufacturing processes that are important when producing water treatment devices, medical adsorbers and the like, for example, durability, robustness (less generation of fine particles), and further, the sterilization resistance of products that causes problems during use. In addition, there has been a demand for further reduction in manufacturing costs.

[0016] To describe the problem to be solved more specifically, poor sterilization resistance leads to the complication of long-time cleaning before use. Most of the above-mentioned known adsorbents contain a large amount of styrene units, which are reaction sites on the base fiber. For this reason, the introduction amount of chloromethyl compound, which is a reaction intermediate, also increases. As a result, the amount of residual chlorine groups that do not react with active induction compounds such as polymyxin also increases. When a large number of chlorine groups are present, hydrochloric acid is gradually eluted into the storage solution over time due to surface hydrolysis that occurs during long-term storage. In fact, it is known that when commercially available fiber materials for blood purification are subjected to autoclave sterilization in physiological saline, chlorine groups are eliminated and the material exhibits acidity of about pH=2. For clinical use, the material must be washed with a large amount of physiological saline in advance, which results in poor usability for users.

[0017] In addition, increasing the amount of chloromethyl compound introduced leads to the consumption of expensive, immobilized activity-inducing compounds more than necessary. To reduce costs, it might be considered to lower the concentration of the activity-inducing compound and perform the immobilization reaction. However, in activity-inducing compounds that have many free amino groups that act as active sites within the molecule, the amino groups that interact with endotoxins, etc., are consumed in the immobilization reaction. As a result, the number of free amino groups decreases, which is a concern as it may lead to a decrease in interaction with endotoxins, etc. Therefore, it is necessary to use a high concentration of the activity-inducing compound during the immobilization reaction, which leads to an increase in the cost of the final product, the liquid purification fiber material.

[0018] Furthermore, if the base material is brittle, a large number of fine particles will be generated during the reaction process in manufacturing and during the filling process into the final form, requiring large amounts of water and effort to remove them. Polystyrene, in particular, is more brittle than polyolefin, and therefore has a higher risk of the outermost polystyrene layer peeling off when force is applied, making it more prone to generating fine particles. For applications involving biological use, the entry of fine particles into the body is strictly limited as stipulated in the pharmacopoeia, and furthermore, as can be seen from the recent problem of marine microplastics, it is necessary to minimize the risk of fine particles being released into the environment.

[0019] The present invention aims to solve the above problems, namely, to provide a liquid purification fiber material that can reduce the amount of washing required and suppress the generation of fine particles, and a washing device equipped therewith. [Means for solving the problem]

[0020] As a result of diligent research into improving these points, the inventors of the present invention have surprisingly discovered that by using a styrene-based block copolymer, it is possible to provide an inexpensive adsorption substrate that exhibits high adsorption performance despite having a lower styrene residue content per unit weight compared to conventional polystyrene substrates, and that generates significantly fewer fine particles (robust) and is resistant to steam sterilization. This has led to the completion of the present invention. Specifically, the details are as follows. (1) A nonwoven fabric substrate according to one embodiment for achieving the above objective is: A nonwoven fabric base material used in liquid purification fibrous materials for removing bio-harmful substances from liquids, which contains a mixed resin of polyolefin and styrene-olefin copolymer within a single fiber, The mass ratio of polyolefin to the mass in the mixed resin is 10% by mass or more and 80% by mass or less. The mass ratio of total styrene residues to the mass of the styrene-olefin copolymer is 5% by mass or more and 50% by mass or less. (2) In a nonwoven fabric substrate according to another embodiment, preferably the mass ratio of polyolefin to the mass in the mixed resin may be 20% by mass or more and 50% by mass or less. (3) In a nonwoven fabric substrate according to another embodiment, preferably, the styrene-olefin copolymer may be at least one copolymer selected from the group consisting of a saturated copolymer obtained by polymerizing an aromatic vinyl compound with an olefin having one double bond, an unsaturated copolymer of an aromatic vinyl compound with a diene having two conjugated double bonds, and a hydrogenated saturated copolymer obtained by hydrogenating the unsaturated copolymer. (4) A liquid purification fiber material according to one embodiment for achieving the above objective is a liquid purification fiber material using any of the above-described nonwoven fabric base materials, A substituent containing a halogen group is introduced as a spacer in the styrene-olefin copolymer. Some of the halogen groups in the spacer are substituted with ligands that interact with biotoxic substances. The halogen content in the liquid purification fiber material is greater than 0 μmol / g and less than or equal to 900 μmol / g relative to the mass of the liquid purification fiber material. (5) In a liquid purification fiber material according to another embodiment, preferably the halogen content in the liquid purification fiber material may be greater than 0 μmol / g and 290 μmol / g or less relative to the mass of the liquid purification fiber material. (6) In a liquid purification fiber material according to another embodiment, preferably the ligand is derived from amino acids, oligopeptides, peptides, sugars, oligopolysaccharides, antibodies, lipopolysaccharides, lipids, proteoglycans, proteins, aptamers and / or polymer electrolytes that interact with biotoxic substances. It has one or more nucleophilic substituents, The nucleophilic substituent may be supported on the styrene-olefin copolymer by chemical bonding between the nucleophilic substituent and the spacer. (7) A method for manufacturing a liquid purification fiber material according to one embodiment for achieving the above objective is a method for manufacturing any of the liquid purification fiber materials described above, A halogenation step is to bring a halogen compound into contact with the nonwoven fabric substrate to obtain a halogenated nonwoven fabric. A ligand loading step is performed to dehalogenate the halogenated nonwoven fabric and support the ligand on the styrene-olefin copolymer. Includes. (8) In a method for producing a liquid purification fiber material according to another embodiment, the ligand may preferably be a polymyxin. (9) A cleaning device according to one embodiment for achieving the above objective is equipped with any of the above-described liquid purification fiber materials inside. [Effects of the Invention]

[0021] According to the present invention, it is possible to provide a liquid purification fiber material that can reduce the amount of washing required and suppress the generation of fine particles, as well as a washing device equipped therewith, at low cost. [Brief explanation of the drawing]

[0022] [Figure 1] Figure 1 shows a longitudinal cross-sectional view of a washing device according to an embodiment of the present invention. [Figure 2] Figure 2 shows the difference spectrum of tryptophan-immobilized fibers. [Figure 3] Figure 3 shows the difference spectrum of arginine-immobilized fibers. [Figure 4] Figure 4 shows the difference spectrum of phenylalanine-immobilized fibers. [Figure 5] Figure 5 shows the difference spectrum of monoethanolamine-immobilized fibers. [Figure 6] Figure 6 shows the difference spectrum of ethylenediamine-immobilized fibers. [Figure 7] Figure 7 shows the difference spectrum of heparin-immobilized fibers. [Figure 8] Figure 8 shows the difference spectrum of azide group-immobilized fibers. [Figure 9] Figure 9 shows the difference spectrum of lactoferrin-heparin immobilized fibers. [Figure 10] Figure 10 shows the XPS measurement results from Experiment 19. [Figure 11] Figure 11 shows the XPS measurement results from Experiment 20. [Explanation of Symbols]

[0023] 1: Container body 2: Bottom 3: Pipe 4: Contact surface 5: Outlet 6: Aperture 7: Inlet 8: Partition plate 9: Stopper 10: Through hole 11: Internal bottom 12: Ligand-immobilized nonwoven fabric 13: Filter 100: Washer [Modes for carrying out the invention]

[0024] Next, embodiments of the present invention will be described. It should be noted that the embodiments described below are not intended to limit the invention as defined in the claims, and not all of the elements and combinations thereof described in the embodiments are necessarily essential to the solution of the present invention.

[0025] <Nonwoven fabric base material> The nonwoven fabric substrate according to an embodiment of the present invention is used as a liquid purification fiber material for adsorbing and recovering biotoxic substances from solutions such as blood, plasma, serum, drugs, cell culture media, and water. This nonwoven fabric substrate is made of a melt-mixed resin of polyolefin and styrene-olefin copolymer, and the blended fibers containing this polyolefin and styrene-olefin copolymer within a single fiber are formed into a nonwoven fabric. The nonwoven fabric substrate has, for example, the form of a sheet. There are no particular restrictions on the planar area of ​​the nonwoven fabric substrate. The thickness of the nonwoven fabric substrate is, for example, 20 μm to 3000 μm.

[0026] The blended fibers of polyolefin and styrene-olefin copolymer preferably have an average diameter of 50 nm to 500 μm, more preferably an average diameter of 80 nm to 40 μm, and even more preferably an average diameter of 100 nm to 30 μm. Furthermore, the blended fibers preferably have an average length of 5 mm or more, more preferably an average length of 10 mm or more, and even more preferably an average length of 20 mm or more. In this application, "average diameter" refers to the average value obtained by randomly observing 100 fields of view of the fiber cross-section using a scanning electron microscope, transmission electron microscope, or digital microscope, calculating the diameter when each cross-section is converted to a circle, and averaging these 100 diameters. Similarly, "average length" refers to the average value obtained by randomly observing 100 fields of view of the fiber side surface using an optical microscope, calculating the length when each fiber is straightened, and averaging these 100 lengths. The same applies to "average diameter" and "average length" as they appear below.

[0027] A styrene-olefin copolymer is a polymer of two or more styrene monomers and two or more olefin monomers, and may be any type of copolymer, such as a block copolymer, random copolymer, alternating copolymer, or graft copolymer, but is preferably a block copolymer. The styrene-olefin copolymer is preferably at least one copolymer selected from the group consisting of a saturated copolymer obtained by polymerizing an aromatic vinyl compound with an olefin having one double bond, an unsaturated copolymer of an aromatic vinyl compound with a diene having two conjugated double bonds, and a hydrogenated saturated copolymer obtained by hydrogenating an unsaturated copolymer.

[0028] The polystyrene blocks constituting the styrene-olefin block copolymer act as physical crosslinking points below the glass transition temperature, exhibiting excellent rubber elasticity. Furthermore, the polyolefin blocks constituting the styrene-olefin block copolymer have fluidity above the glass transition temperature, contributing to easy processability. Suitable examples of styrene-olefin block copolymers include diblock types having the form of PS-PO and triblock types having the form of PS-PO-PS. Here, "PS" means polystyrene, and "PO" means polyolefin. Preferably, the styrene-olefin copolymer is a hydrogenated styrene-olefin copolymer, more preferably at least one copolymer selected from the group consisting of styrene-ethylene / butylene-styrene block copolymer (hereinafter sometimes abbreviated as "SEBS"), styrene-ethylene / propylene-styrene block copolymer (hereinafter sometimes abbreviated as "SEPS"), and styrene-(ethylene-ethylene / propylene)-styrene block copolymer (hereinafter sometimes abbreviated as "SEEPS"), and even more preferably SEBS.

[0029] The mass ratio of polyolefin in the blended fibers is 10% by mass or more and 80% by mass or less, preferably 20% by mass or more and 50% by mass or less, more preferably 25% by mass or more and 50% by mass or less, and even more preferably 30% by mass or more and 50% by mass or less. Styrene-olefin copolymers tend to break easily when melt-spun on their own, but the spinnability is improved by melt-mixing them with polyolefin.

[0030] The mass ratio of total styrene residues to the mass of the styrene-olefin copolymer is 5% by mass or more and 50% by mass or less, preferably 10% by mass or more and 40% by mass, more preferably 10% by mass or more and 30% by mass or less, and even more preferably 10% by mass or more and 25% by mass or less. Setting the mass ratio of total styrene residues to the mass of the styrene-olefin copolymer to 5% by mass or more and 50% by mass or less limits the number of benzene rings that are the groups to which halogen groups are introduced, thereby suppressing the amount of halogen groups and further reducing the amount of fine particles generated by suppressing the brittleness of the nonwoven fabric. Furthermore, even if the amount of halogen groups is reduced, sufficient ligands for adsorbing biotoxic substances (endotoxins, for example) can be introduced, so the amount of ligands required for the manufacture of fiber materials for liquid purification can be reduced, thereby reducing the cost of fiber materials for liquid purification. Here, "halogen" is interpreted as meaning the removal of halogens from the polymer when a ligand-immobilized nonwoven fabric (nonwoven fabric for liquid purification) is made using a nonwoven fabric base material that was originally made by mixing a polymer containing halogens. In addition to endotoxins, biologically harmful substances also include enterotoxins, bilirubin, abnormal cells such as cancer cells and white blood cells in the blood, immunogenic substances, excess essential elements, proteins, lipids, bile acids, viruses, bacteria and their spores, endocrine disruptors, heavy metals (including iron), and substances that cause various diseases, such as amyloid-beta, which is the causative agent of Alzheimer's disease.

[0031] <Method for manufacturing nonwoven fabric substrates> Nonwoven fabric substrates can be manufactured by any method that allows polyolefins and styrene-olefin copolymer mixed fibers to form a nonwoven substrate. More preferred manufacturing methods are the meltblown method, the needle punch method, and the electrospinning method. Each of these manufacturing methods will be described below.

[0032] (1) Meltblown process Polyolefin and styrene-olefin copolymer are melted and mixed, then flowed towards a drum using air pressure from a nozzle with a series of fine pores. As a result, a nonwoven fabric is produced consisting of fibers in which polyolefin and styrene-olefin copolymer are mixed within a single fiber. Since no binder is used, a nonwoven fabric consisting solely of fibers of the mixed resin is obtained.

[0033] (2) Needle punching method Nonwoven fabric is manufactured by layering thin, multiple layers of fibers made from a mixture of polyolefin and styrene-olefin copolymer, and then compressing them with a machine equipped with needles. This method involves using the needles to pull up the fibers and entangle them with each other.

[0034] (3) Electrospinning This method is also called electrospinning. The spinning apparatus is equipped with a DC high-voltage power supply, a spinneret, and a collector. Polyolefins and styrene-olefin copolymers are melt-mixed, and the resulting polymer solution is extruded through a spinneret to which a high voltage is applied. Each extruded polymer solution becomes a fiber with a nanometer diameter, which reaches a grounded collector and forms a nonwoven fabric.

[0035] Furthermore, the nonwoven fabric substrate according to this embodiment can be manufactured using methods other than those described above, such as the airlaid method, the spunbond method, or a wet method similar to papermaking.

[0036] <Fiber materials for liquid purification> The liquid purification fiber material according to this embodiment is obtained by introducing a ligand that interacts with biotoxic substances into the aforementioned nonwoven fabric substrate. Specifically, in this liquid purification fiber material, a halogen-containing compound is introduced as a linker to the styrene residues of the styrene-olefin copolymer constituting the aforementioned nonwoven fabric, and the halogen on the linker is further removed to support the ligand. In other words, in the liquid purification fiber material, substituents containing halogen groups are introduced as spacers into the styrene-olefin copolymer, and some of the halogen groups of these spacers are replaced with ligands that interact with biotoxic substances.

[0037] The ligand is preferably more than 0 μmol and 600 μmol or less, more preferably 0.02 μmol to 290 μmol, even more preferably 0.02 μmol to 15 μmol, and particularly more preferably 0.04 μmol to 12.5 μmol per gram of dry mass of the liquid purification fiber material. The liquid purification fiber material may contain halogens because a halogen-containing linker is added to styrene during the manufacturing process. The halogen content in the liquid purification fiber material is preferably more than 0 μmol / g and 900 μmol / g or less, more preferably more than 0 μmol / g and 600 μmol / g or less, even more preferably more than 0 μmol / g and 290 μmol / g or less, even more preferably more than 0 μmol / g and 200 μmol / g or less, even more preferably more than 0 μmol / g and 150 μmol / g or less, even more preferably more than 0 μmol / g and 100 μmol / g or less, and particularly more preferably more than 0 μmol / g and 50 μmol / g or less, relative to the mass of the liquid purification fiber material. In this context, "halogen" refers to the absence of halogens in polymers when a ligand-immobilized nonwoven fabric (nonwoven fabric for liquid purification) is manufactured using a nonwoven fabric substrate that originally contains halogens. This lower halogen content compared to conventional products reduces the number of times users need to wash the product, resulting in easier use.

[0038] Ligands that interact with biotoxic substances are, for example, derived from amino acids, oligopeptides, peptides, sugars, oligopolysaccharides, polysaccharides, antibodies, lipopolysaccharides, lipids, proteoglycans, proteins, aptamers and / or polymer electrolytes, but are not limited to those that have one or more nucleophilic substituents that react with the halogen of the linker. Examples of such nucleophilic substituents include amino groups, alkoxy groups, thiolate groups and acetylide groups. Exemplary ligands include tryptophan, L( + Examples of ligands include arginine, phenylalanine, monoethanolamine, ethylenediamine, heparin, azide groups, lactoferrin, and gelatin. Ligands are preferably those having an amino group that has adsorption capacity for endotoxins. Ligands are, for example, antibiotics or cationic polymers such as polylysine or polyethyleneimine. As antibiotics, peptide compounds such as polymyxins and histatines are preferred, with low molecular weight peptides being more preferred, and polymyxins being particularly preferred. Examples of polymyxins include polymyxin A, polymyxin B1, polymyxin B2, polymyxin D1, polymyxin E1, and polymyxin E2. Salts such as sulfates and hydrochlorides of these can also be used. Ligands may be used individually or in combination of two or more of the above examples. Ligands are supported on a styrene-olefin copolymer by chemical bonding between the nucleophilic substituent and a spacer.

[0039] <Method for manufacturing fiber materials for liquid purification> The liquid purification fiber material according to this embodiment can be manufactured through the following halogenation step and ligand loading step.

[0040] The method for producing a liquid purification fiber material according to this embodiment is a method for producing any of the liquid purification fiber materials described above, and includes a halogenation step of contacting a nonwoven fabric substrate with a halogen-containing compound to obtain a halogenated nonwoven fabric, and a ligand-supporting step of dehalogenating the halogenated nonwoven fabric and supporting a ligand on a styrene-olefin copolymer. Each step will be described in more detail below.

[0041] (1) Halogenation process A container is filled with a nonwoven fabric substrate, 2-chloro-N-(hydroxymethyl)acetamide (an example of a halogen compound), paraformaldehyde, nitrobenzene, and concentrated sulfuric acid. The mixture is stirred to react the halogen-containing compounds with the styrene residues in the styrene-olefin copolymer that constitutes the nonwoven fabric substrate. Next, the nonwoven fabric is removed from the container and washed with distilled water and methanol. After that, the nonwoven fabric is dried to obtain a chlorinated nonwoven fabric (an example of a halogenated nonwoven fabric; the same applies hereinafter) in which the halogen-containing compound is immobilized on the styrene.

[0042] (2) Ligand loading process In a container, the chlorinated nonwoven fabric and a pH adjuster are added to a solution obtained by mixing the ligand or a salt thereof with distilled water and then stirred. Next, the nonwoven fabric is removed from the container and washed with distilled water to remove unreacted ligand and free hydrochloric acid. After that, it is dried to obtain a ligand-supported nonwoven fabric. In this process, the chloro groups of the chlorinated nonwoven fabric are removed to become hydrochloric acid, and the ligand binds to the chloro group sites. Multiple types of ligands can also be attached in this process. For example, to immobilize another ligand Y on a nonwoven fabric immobilized with ligand X, ligand Y is dissolved in distilled water to prepare an aqueous solution of ligand Y, the ligand X-immobilized nonwoven fabric is placed in it and stirred for a predetermined time, rinsed several times with distilled water, and then dried to obtain a nonwoven fabric immobilized with ligand X and ligand Y. An example of ligand X is heparin. An example of ligand Y is lactoferrin.

[0043] <Washing device> A cleaning device according to an embodiment of the present invention is a device that incorporates the aforementioned liquid purification fiber material inside. The cleaning device is, for example, a blood purifier. The liquid purification fiber material is provided inside the blood purifier as a blood purification fiber material. Both the blood purification fiber material and the blood purifier are autoclavable. Another example of a cleaning device is a liquid cleaning device for purifying liquid pharmaceuticals or liquid pharmaceutical raw materials. Both the liquid purification fiber material and the liquid cleaning device are autoclavable. Yet another example of a cleaning device is a waste liquid cleaning device for preventing the discharge of biotoxic substances into the environment. The liquid purification fiber material is provided inside the waste liquid cleaning device as a waste liquid purification fiber material. Both the waste liquid purification fiber material and the waste liquid cleaning device are autoclavable.

[0044] Figure 1 shows a longitudinal cross-sectional view of a washing device according to an embodiment of the present invention.

[0045] The washing device 100 has, for example, the following structure. The container body 1 of the washing device 100 has a pipe 3 passing through its bottom 2 and welded and fixed at the contact surface 4. An outlet 5 is provided at the top of the container body 1. Openings 6 and inlets 7 are provided at both the top and bottom ends of the pipe 3. The openings 6 are sealed by stoppers 9 provided on the partition plate 8. A flow path for guiding liquid is formed on the inside of the pipe 3, and numerous through holes 10 are provided on its peripheral wall. Ligand-immobilized nonwoven fabric 12 is wrapped around the pipe 3 in multiple layers between the partition plate 8 and the inner bottom surface 11 of the container body 1. A filter 13 is provided inside the outlet 5.

[0046] An example of using the cleaning device 100 is as follows: A liquid containing biologically harmful substances flows in through the opening 7 via the flow path a1, passes through the flow path a2 inside the pipe, and is discharged radially from the through-hole 10. The liquid flows radially a3 through the multi-layer ligand-immobilized nonwoven fabric (corresponding to a liquid purification fiber material) 12, is purified, passes through the gap a4 between the outermost layer of the nonwoven fabric 12 and the inner surface of the container body 1, and fine particles are removed by the filter 13. In this way, the purified liquid is recovered from the outlet hole 5 (a5).

[0047] According to the above embodiment, it is possible to provide a liquid purification fiber material and a cleaning device equipped therewith that can reduce the amount of washing required and suppress the generation of fine particles at a low cost. Furthermore, according to a part of the above embodiment, it is possible to provide a liquid purification fiber material and a cleaning device equipped therewith that also have excellent adsorption performance for biologically harmful components. [Examples]

[0048] Next, embodiments of the present invention will be described in detail, using polymyxin immobilization as an example. However, the present invention is not limited to the following embodiments.

[0049] "Experiment 1" (1) Manufacturing of nonwoven fabrics <Manufacturing Example 1> Sixty parts by mass (6 kg) of styrene-ethylene / butylene-styrene polymer (SEBS, Kraton Corporation, product code MD1648), containing 20% ​​by mass of styrene residues and 80% by mass of ethylene / butylene residues, was mixed with 40 parts by mass (4 kg) of polypropylene (LyondellBasell Industries, product code MOPLEN HP461X). Using an AIKI Riotec ALM-MB instrument, the mixture was spun and a nonwoven fabric (3000 mm long x 250 mm wide x 0.3 mm thick) was produced by the melt-blown method. This nonwoven fabric is referred to as "Nonwoven Fabric A". The chlorine content in Nonwoven Fabric A was measured by combustion ion chromatography and found to be less than 0.001 w / w% (0.2 μmol / g).

[0050] (2) Chlorination of nonwoven fabrics <Manufacturing Example 2> In a polypropylene container (50 mL), 0.214 g of 2-chloro-N-(hydroxymethyl)acetamide (BLDP-05742, manufactured by BLD Pharm), 0.011 g of paraformaldehyde (product code 168-20955, manufactured by Fujifilm Wako Pure Chemical Industries), 20 ml of nitrobenzene (product code 143-01706, manufactured by Fujifilm Wako Pure Chemical Industries), 1 ml of 95% concentrated sulfuric acid (product code 192-04696, manufactured by Fujifilm Wako Pure Chemical Industries), and 1 g of nonwoven fabric A were placed and the mixture was stirred by inversion at room temperature of 24°C for 3 hours. Next, the nonwoven fabric was removed from the container, washed with distilled water and methanol, and then the remaining washing solution was dried off in a vacuum dryer at 85°C to obtain chlorinated nonwoven fabric A. When the amount of chlorine in the nonwoven fabric was measured by combustion ion chromatography, the chlorine content was found to be 0.151 w / w% (43 μmol / g). <Manufacturing Example 3> Nonwoven fabric A was chlorinated under the same conditions as in Production Example 2, except that the amount of concentrated sulfuric acid was increased to 2 ml, to obtain chlorinated nonwoven fabric B. The amount of chlorine in the nonwoven fabric was measured by combustion ion chromatography, and the amount of chlorine was found to be 0.131 w / w% (37 μmol / g). <Manufacturing Example 4> Nonwoven fabric A was chlorinated under the same conditions as in Production Example 3, except that the amount of concentrated sulfuric acid was increased to 15 ml, to obtain chlorinated nonwoven fabric C. The amount of chlorine in the nonwoven fabric was measured by combustion ion chromatography, and the amount of chlorine was found to be 0.096 w / w% (27 μmol / g). <Manufacturing Example 5> In a Pyrex® container (50 mL), 0.214 g of 2-chloro-N-(hydroxymethyl)acetamide (same as in Production Example 2), 0.011 g of paraformaldehyde (same as in Production Example 2), 20 ml of nitrobenzene (same as in Production Example 2), 2 mL of 95% concentrated sulfuric acid (same as in Production Example 2), and 1 g of nonwoven fabric A were placed and stirred at room temperature of 24 °C using a magnetic stirrer. Next, the nonwoven fabric was removed, washed with distilled water and methanol, and then the remaining washing solution was dried off in a vacuum dryer at 85 °C to obtain chlorinated nonwoven fabric D. The amount of chlorine in the nonwoven fabric was measured by combustion ion chromatography and found to be 0.095 w / w% (27 μmol / g). <Manufacturing Example 6> In a Pyrex® container (50 mL), 0.214 g of 2-chloro-N-(hydroxymethyl)acetamide (same as in Production Example 2), 0.011 g of paraformaldehyde (same as in Production Example 2), 20 ml of nitrobenzene (same as in Production Example 2), 2 ml of 95% concentrated sulfuric acid (same as in Production Example 2), and 1 g of nonwoven fabric A were placed and stirred in a 24°C water bath using a magnetic stirrer. Next, the nonwoven fabric was removed, washed with distilled water and methanol, and then the remaining washing solution was dried off in a vacuum dryer at 85°C to obtain chlorinated nonwoven fabric E. The amount of chlorine in the nonwoven fabric was measured by combustion ion chromatography and found to be 0.073 w / w% (21 μmol / g). <Manufacturing Example 7> Chlorinated nonwoven fabric F was obtained under the same conditions as in Production Example 6, except that the temperature in the water bath was set to 20°C. The amount of chlorine in the nonwoven fabric was measured by combustion ion chromatography, and the amount of chlorine was found to be 0.039 w / w% (11 μmol / g). <Manufacturing Example 8> Chlorinated nonwoven fabric G was obtained under the same conditions as in Production Example 6, except that the temperature in the water bath was set to 14°C. The amount of chlorine in the nonwoven fabric was measured by combustion ion chromatography, and the amount of chlorine was found to be 0.019 w / w% (5 μmol / g). <Manufacturing Example 9> Chlorinated nonwoven fabric H was obtained under the same conditions as in Production Example 6, except that the temperature in the water bath was set to 5°C. The amount of chlorine in the nonwoven fabric was measured by combustion ion chromatography, and the amount of chlorine was found to be 0.011 w / w% (3 μmol / g). <Production example 9A> Chlorinated nonwoven fabric H' was obtained under the same conditions as in Production Example 6, except that the temperature in the water bath was set to 50°C. The amount of chlorine in the nonwoven fabric was measured by combustion ion chromatography, and the amount of chlorine was found to be 0.52 w / w% (146 μmol / g).

[0051] (3) Polymyxination of chlorinated nonwoven fabrics <Example 1> In the polypropylene container used in Production Example 2, 15 mg of polymyxin B sulfate (CAYMAN CHEMICAL COMPANY, product code 1-800-364-9897) was weighed out and dissolved in 15 ml of distilled water. To this reaction solution, 1 g of chlorinated nonwoven fabric B and 2 mg of pH-adjusting magnesium oxide (FUJIFILM Wako Pure Chemical Industries, product code 131-00282) were added and the mixture was stirred by inversion at room temperature of 25°C for 2 hours to allow the reaction to proceed. Next, the nonwoven fabric was removed, washed with hydrochloric acid and distilled water, and then dried in a forced-air dryer at 40°C for 3 hours to obtain polymyxin-supported nonwoven fabric A. <Example 2> Polymyxin-supported nonwoven fabric B was obtained under the same conditions as in Example 1, except that the amount of polymyxin B sulfate was 1 mg. <Example 3> Using chlorinated nonwoven fabric G, polymyxin-supported nonwoven fabric C was obtained under the same conditions as in Example 1, except that 1 mg of polymyxin B sulfate was added. <Example 4> Polymyxin-supported nonwoven fabric D was obtained under the same conditions as in Example 1, except that the amount of polymyxin B sulfate was 0.05 mg.

[0052] "Characteristic Evaluation 1" The various properties of polymyxin-supported nonwoven fabrics A, B, C, and D were evaluated. Toray Industries, Inc.'s "Toremyxin PMX-20R" was used as a comparative material. Toray Industries, Inc.'s "Toremyxin PMX-20R" does not have a nonwoven fabric structure; instead, it consists of woven fibers with styrene coated on the surface of polypropylene. Therefore, it contains a high amount of chlorine.

[0053] (1) Amount of polymyxin added during the reaction Table 1 shows the amount of polymyxin added during the production of various polymyxin-supported nonwoven fabric samples.

[0054] [Table 1]

[0055] (2) Fine particle measurement Table 2 compares the number of particulate matter generated when polymyxin-supported nonwoven fabric B and a comparison material were subjected to two different treatments. The samples measured were 0.17 g each of polymyxin-supported nonwoven fabric B and the comparison material, cut into 2 cm squares. Each sample was placed in a 50 ml vial and washed by rinsing 10 times with 10 ml of physiological saline. This removed the fibrils generated during cutting. Next, after drying each sample, 10 ml of physiological saline was added and the samples were inverted and stirred in a rotator for 2 hours (rotation speed: 10 rpm). Alternatively, after drying each sample, 10 ml of physiological saline was added and ultrasonic cleaning (frequency: 40 kHz) was performed for 20 minutes. The samples treated by these two methods were then diluted and subjected to a particle counter (Beckman Coulter, model: HIAC 9703+; the same was used for subsequent particle measurements).

[0056] [Table 2]

[0057] As is clear from Table 2, in both treatment cases, Sample B generated fewer fine particles compared to the comparison material.

[0058] (3) Chlorine content Table 3 compares the chlorine content of various samples A, B, C, D, and a comparison material. Chlorine content was measured by combustion ion chromatography. Specifically, samples were combusted and aspirated using a combustion / suction system (model SQ-10) manufactured by Yanako Instruments Development Laboratory, and then separated and analyzed using an ion chromatography system (model ICA2000) and column (TSK-gel Super IC-Anion HS) manufactured by Toa DKK Corporation. The same procedure was followed for subsequent chlorine content measurements.

[0059] [Table 3]

[0060] As is clear from Table 3, all of samples A, B, C, and D were found to contain less chlorine than the comparison material.

[0061] (4) Change in pH after autoclaving 100 mg each of sample B and the comparison material were washed with deionized water, dried, and then sterilized in 10 ml of physiological saline using an autoclave (Hirayama Seisakusho, model: HV-85IILV; the same autoclave was used for subsequent measurements) at 121°C for 20 min. The change in pH of the physiological saline before and after sterilization was examined. The physiological saline of sample B changed from pH 7.2 to 6.9. The physiological saline of the comparison material changed from pH 7.2 to 3.7. A pH meter (Hanna Instruments, model: HI 2020-01) was used for subsequent pH measurements. From these results, it is considered that in the case of sample D, the pH change of the physiological saline was smaller and the amount of chlorine removed was less compared to the comparison material. This result suggests that sample B has the potential to significantly simplify the pre-use rinsing process compared to the comparison material.

[0062] (5) Adsorption capacity of endotoxins in water Table 4 shows the results of adsorption treatment of various samples (25 mg each) with endotoxin (100 EU / ml × 20 ml) in water. The adsorption capacity of endotoxin was measured by turbidimetric time analysis. Limulus ES-2 Single Test Wako, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., was used as the reagent for the analysis, and a Toxinometer ET-7000, also manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., was used for the measurement. The same method was used when investigating the adsorption capacity of endotoxin or other biologically harmful substances thereafter. The removal rate (%) in the table is calculated by multiplying (blank concentration - measured concentration) / blank concentration by 100.

[0063] [Table 4]

[0064] All samples A, B, C, and D showed a higher removal rate than the control material in both 2-hour and 4-hour adsorption tests.

[0065] (6) Adsorption capacity of endotoxins in human serum Table 5 shows the results of adsorption treatment of endotoxin (100 EU / ml × 3 ml) from human serum using 15 mg of various samples. The removal rate (%) in the table is calculated by multiplying (blank concentration - measured concentration) / blank concentration by 100.

[0066] [Table 5]

[0067] Each sample (A, B, C, and D) showed a higher removal rate than the comparison material in both 20-minute and 60-minute adsorption tests.

[0068] "Experiment 2" (1) Manufacturing of nonwoven fabrics <Manufacturing Example 10> Sixty parts by mass (6 kg) of styrene-ethylene / butylene-styrene polymer (SEBS, Kraton Corporation, product code G1657), containing 10% by weight of styrene residues and 90% by weight of ethylene / butylene residues, was mixed with 40 parts by mass (4 kg) of polypropylene (Sun Allomer Corporation, product code PWH02N). Using an AIKI Riotec ALM-MB instrument, the mixture was spun and a nonwoven fabric (3000 mm long x 250 mm wide x 0.3 mm thick) was produced by the melt-blown method. This nonwoven fabric is referred to as "Nonwoven Fabric I". The chlorine content in Nonwoven Fabric I was measured by combustion ion chromatography and found to be less than 0.2 μmol / g.

[0069] (2) Chlorination of nonwoven fabrics <Manufacturing Example 11> In a polypropylene container (50 mL), 0.214 g of 2-chloro-N-(hydroxymethyl)acetamide (BLDP-05742, manufactured by BLD Pharm), 0.068 g of paraformaldehyde (product code 168-20955, manufactured by Fujifilm Wako Pure Chemical Industries), 20 mL of nitrobenzene (product code 143-01706, manufactured by Fujifilm Wako Pure Chemical Industries), 2 mL of 95% concentrated sulfuric acid (product code 192-04696, manufactured by Fujifilm Wako Pure Chemical Industries), and 1 g of nonwoven fabric I were placed, and the mixture was stirred by inversion at room temperature of 25°C for 3 hours. Next, the nonwoven fabric was removed from the container, washed with distilled water and methanol, and then dried in a forced-air dryer at 40°C for 3 hours to obtain chlorinated nonwoven fabric I.

[0070] (3) Polymyxination of chlorinated nonwoven fabrics <Example 5> 15 mg of polymyxin B sulfate (CAYMAN CHEMICAL COMPANY, product code 1-800-364-9897) was weighed into a polypropylene container (50 mL) and dissolved in 15 mL of distilled water. 1 g of chlorinated nonwoven fabric I and 2 mg of pH-adjusting magnesium oxide (FUJIFILM Wako Pure Chemical Industries, product code 131-00282) were added to the reaction solution and the mixture was stirred by inversion at room temperature (25°C) for 2 hours. Next, the nonwoven fabric was removed, washed with hydrochloric acid and distilled water, and then dried in a forced-air dryer at 40°C for 3 hours to obtain polymyxin-supported nonwoven fabric I.

[0071] "Experiment 3" (1) Manufacturing of nonwoven fabrics <Manufacturing Example 12> Sixty parts by mass (6 kg) of styrene-ethylene / butylene-styrene polymer (SEBS, Kraton Corporation, product code MD1648), containing 20% ​​by weight of styrene residues and 80% by weight of ethylene / butylene residues, was mixed with 40 parts by mass (4 kg) of polypropylene (Sun Allomer Corporation, product code PWH02N). Using an AIKI Riotec ALM-MB instrument, the mixture was spun and a nonwoven fabric (3000 mm long x 250 mm wide x 0.3 mm thick) was produced by the melt-blown method. This nonwoven fabric is referred to as "Nonwoven Fabric J". The chlorine content in Nonwoven Fabric J was measured by combustion ion chromatography and found to be less than 0.2 μmol / g.

[0072] (2) Chlorination of nonwoven fabrics <Manufacturing Example 13> Chlorination was carried out under the same conditions as in Production Example 11, except that 1 g of nonwoven fabric J was substituted for 1 g of nonwoven fabric I, to obtain chlorinated nonwoven fabric J.

[0073] (3) Polymyxination of chlorinated nonwoven fabrics <Example 6> Polymyxination was performed under the same conditions as in Example 5, except that 1 g of chlorinated nonwoven fabric J was used instead of 1 g of chlorinated nonwoven fabric I, to obtain polymyxin-supported nonwoven fabric J.

[0074] "Experiment 4" (1) Manufacturing of nonwoven fabrics <Manufacturing Example 14> 60 parts by mass (6 kg) of styrene-ethylene / propylene-styrene polymer (SEPS, product code Septon 2002, manufactured by Kuraray Co., Ltd.), containing 30% by weight of styrene residues and 70% by weight of ethylene / propylene residues, was mixed with 40 parts by mass (4 kg) of polypropylene (product code PWH02N, manufactured by Sun Allomer). Using an ALM-MB instrument manufactured by AIKI Riotec, the mixture was spun and a nonwoven fabric (3000 mm long x 250 mm wide x 0.3 mm thick) was produced by the melt-blown method. This nonwoven fabric is referred to as "Nonwoven Fabric K". The amount of chlorine in Nonwoven Fabric K was measured by combustion ion chromatography and found to be less than 0.2 μmol / g.

[0075] (2) Chlorination of nonwoven fabrics <Manufacturing Example 15> Chlorination was carried out under the same conditions as in Production Example 11, except that 1 g of nonwoven fabric K was added instead of 1 g of nonwoven fabric I, to obtain chlorinated nonwoven fabric K.

[0076] (3) Polymyxination of chlorinated nonwoven fabrics <Example 7> Polymyxination was performed under the same conditions as in Example 5, except that 1 g of chlorinated nonwoven fabric K was used instead of 1 g of chlorinated nonwoven fabric I, to obtain polymyxin-supported nonwoven fabric K.

[0077] "Experiment 5" (1) Manufacturing of nonwoven fabrics <Manufacturing Example 16> Sixty parts by mass (6 kg) of styrene-ethylene / butylene-styrene polymer (SEBS, product code ToughTec H1517, manufactured by Asahi Kasei Corporation), containing 43% by weight of styrene residues and 57% by weight of ethylene / butylene residues, was mixed with 40 parts by mass (4 kg) of polypropylene (product code PWH02N, manufactured by Sun Allomer). Using an ALM-MB instrument manufactured by AIKI Riotec, the mixture was spun and a nonwoven fabric (3000 mm long x 250 mm wide x 0.3 mm thick) was produced by the melt-blown method. This nonwoven fabric is referred to as "Nonwoven Fabric L". The amount of chlorine in Nonwoven Fabric L was measured by combustion ion chromatography and found to be less than 0.2 μmol / g.

[0078] (2) Chlorination of nonwoven fabrics <Manufacturing Example 17> Chlorination was carried out under the same conditions as in Production Example 11, except that 1 g of nonwoven fabric L was substituted for 1 g of nonwoven fabric I, to obtain chlorinated nonwoven fabric L.

[0079] (3) Polymyxination of chlorinated nonwoven fabrics <Example 8> Polymyxination was performed under the same conditions as in Example 5, except that 1 g of chlorinated nonwoven fabric L was used instead of 1 g of chlorinated nonwoven fabric I, to obtain polymyxin-supported nonwoven fabric L.

[0080] "Characteristic Evaluation 2" The various properties of polymyxin-supported nonwoven fabrics I, J, K, and L were evaluated. Toray Industries, Inc.'s "Toremyxin PMX-20R" was used as a comparative material. In property evaluation 2, conditions not specifically mentioned are the same as in property evaluation 1.

[0081] (1) Fine particle measurement Tables 6 and 7 show a comparison of the number of fine particles generated when polymyxin-supported nonwoven fabrics I, J, K, and L and a comparison material were subjected to two different treatments. The samples measured were the four polymyxin-supported nonwoven fabrics and one comparison material, each cut into 2 cm squares. Each sample was placed in a 50 mL vial and washed by rinsing 10 times with 10 mL of physiological saline. This removed the fibrils generated during cutting. Next, after drying each sample, 10 mL of physiological saline was added and the samples were inverted and stirred in a rotator for 2 hours (rotation speed: 10 rpm). Alternatively, after drying each sample, 10 mL of physiological saline was added and ultrasonic cleaning (frequency: 40 kHz) was performed for 20 minutes. The samples treated by these two methods were then diluted and subjected to a particle counter. The results for the samples inverted and stirred in a rotator are shown in Table 6, and the results for the samples ultrasonically cleaned are shown in Table 7. As is clear from Tables 6 and 7, in both treatment cases, each sample from Examples 5 to 8 generated less fine particles compared to the comparative material.

[0082] [Table 6]

[0083] [Table 7]

[0084] (2) Chlorine content Table 8 compares the chlorine content of polymyxin-supported nonwoven fabrics I, J, K, and L, and the comparative material after autoclaving. The chlorine content was measured by combustion ion chromatography. As is clear from Table 8, each sample from Examples 5 to 8 was found to contain a lower chlorine content than the comparative material.

[0085] [Table 8]

[0086] (3) Change in pH after autoclaving Table 9 shows the pH change of physiological saline before and after autoclaving polymyxin-supported nonwoven fabrics I, J, and L, and the comparative material. 100 mg each of the polymyxin-supported nonwoven fabrics and the comparative material were washed with deionized water, dried, and then autoclaved in 10 mL of physiological saline (121°C, 20 min). The physiological saline before and after sterilization was measured using a pH meter. These results suggest that the samples from each example may allow for a significantly simpler pre-use rinsing process compared to the comparative material.

[0087] [Table 9]

[0088] (4) Adsorption capacity of endotoxins in water Table 10 shows the results of adsorption treatment of 25 mg each of polymyxin-supported nonwoven fabrics I, J, K, and the comparative material with endotoxin in water (100 EU / mL × 20 mL) after autoclaving. The adsorption rate (%) in the table is calculated by multiplying (blank concentration - measured concentration) / blank concentration by 100. "Adsorption rate" can also be referred to as "removal rate". As is clear from Table 10, the samples from each example were found to have higher adsorption capacity compared to the comparative material.

[0089] [Table 10]

[0090] (5) Adsorption capacity of endotoxins in human serum Table 11 shows the results of adsorption treatment of endotoxin (100 EU / mL × 3 mL) from serum onto 15 mg each of polymyxin-supported nonwoven fabric J and the comparative material after autoclaving. The adsorption rate (%) in the table is calculated by multiplying (blank concentration - measured concentration) / blank concentration by 100. "Adsorption rate" can also be referred to as "removal rate". As is clear from Table 11, the samples from each example were found to have higher adsorption capacity compared to the comparative material.

[0091] [Table 11]

[0092] "Experiment 6" (1) Manufacturing of nonwoven fabrics <Manufacturing Example 18> 20 parts by mass (2 kg) of styrene-ethylene / butylene-styrene polymer (SEBS, Kraton Corporation, product code G1657), containing 10% by weight of styrene residues and 90% by weight of ethylene / butylene residues, was mixed with 80 parts by mass (8 kg) of polypropylene (Sun Allomer Corporation, product code PWH02N). Using an AIKI Riotec ALM-MB instrument, the mixture was spun and a nonwoven fabric (3000 mm long x 250 mm wide x 0.3 mm thick) was produced by the melt-blown method. This nonwoven fabric is referred to as "Nonwoven Fabric M". The chlorine content in Nonwoven Fabric M was measured by combustion ion chromatography and found to be less than 0.2 μmol / g.

[0093] (2) Chlorination of nonwoven fabrics <Manufacturing Example 19> In a 50 mL polypropylene container, 0.214 g of 2-chloro-N-(hydroxymethyl)acetamide (BLDP-05742, manufactured by BLD Pharm), 0.068 g of paraformaldehyde (product code 168-20955, manufactured by Fujifilm Wako Pure Chemical Industries), 20 mL of nitrobenzene (product code 143-01706, manufactured by Fujifilm Wako Pure Chemical Industries), 2 mL of 95% concentrated sulfuric acid (product code 192-04696, manufactured by Fujifilm Wako Pure Chemical Industries), and 1 g of nonwoven fabric M were placed, and the mixture was stirred by inversion at room temperature of 25°C for 3 hours. Next, the nonwoven fabric was removed from the container, washed with distilled water and methanol, and then dried in a forced-air dryer at 40°C for 3 hours to obtain chlorinated nonwoven fabric M.

[0094] (3) Polymyxination of chlorinated nonwoven fabrics <Example 9> 15 mg of polymyxin B sulfate (CAYMAN CHEMICAL COMPANY, product code 1-800-364-9897) was weighed into a polypropylene container (50 mL) and dissolved in 15 mL of distilled water. 1 g of chlorinated nonwoven fabric M and 2 mg of pH-adjusting magnesium oxide (FUJIFILM Wako Pure Chemical Industries, product code 131-00282) were added to the reaction solution and the mixture was stirred by inversion at room temperature (25°C) for 2 hours. Next, the nonwoven fabric was removed, washed with hydrochloric acid and distilled water, and then dried in a forced-air dryer at 40°C for 3 hours to obtain polymyxin-supported nonwoven fabric M.

[0095] "Experiment 7" (1) Manufacturing of nonwoven fabrics <Manufacturing Example 20> 20 parts by mass (2 kg) of styrene-ethylene / butylene-styrene polymer (SEBS, Kraton Corporation, product code MD1648), containing 20% ​​by weight of styrene residues and 80% by weight of ethylene / butylene residues, was mixed with 80 parts by mass (8 kg) of polypropylene (Sun Allomer Corporation, product code PWH02N). Using an AIKI Riotec ALM-MB instrument, the mixture was spun and a nonwoven fabric (3000 mm long x 250 mm wide x 0.3 mm thick) was produced by the melt-blown method. This nonwoven fabric is referred to as "Nonwoven Fabric N". The chlorine content in Nonwoven Fabric N was measured by combustion ion chromatography and found to be less than 0.2 μmol / g.

[0096] (2) Chlorination of nonwoven fabrics <Manufacturing Example 21> Chlorination was performed under the same conditions as in Production Example 19, except that 1 g of nonwoven fabric N was substituted for 1 g of nonwoven fabric M, to obtain chlorinated nonwoven fabric N.

[0097] (3) Polymyxination of chlorinated nonwoven fabrics <Example 10> Polymyxination was performed under the same conditions as in Example 9, except that 1 g of chlorinated nonwoven fabric N was used instead of 1 g of chlorinated nonwoven fabric M, to obtain polymyxin-supported nonwoven fabric N.

[0098] "Experiment 8" (1) Manufacturing of nonwoven fabrics <Manufacturing Example 22> 90 parts by mass (9 kg) of styrene-ethylene / butylene-styrene polymer (SEBS, Kraton Corporation, product code MD1648), containing 20% ​​by weight of styrene residues and 80% by weight of ethylene / butylene residues, was mixed with 10 parts by mass (1 kg) of polypropylene (Sun Allomer Corporation, product code PWH02N). Using an AIKI Riotec ALM-MB instrument, the mixture was spun and a nonwoven fabric (3000 mm long x 250 mm wide x 0.3 mm thick) was produced by the melt-blown method. This nonwoven fabric is referred to as "Nonwoven Fabric O". The chlorine content in Nonwoven Fabric O was measured by combustion ion chromatography and found to be less than 0.2 μmol / g.

[0099] (2) Chlorination of nonwoven fabrics <Manufacturing Example 23> Chlorination was carried out under the same conditions as in Production Example 19, except that 1 g of nonwoven fabric O was substituted for 1 g of nonwoven fabric M, to obtain chlorinated nonwoven fabric O.

[0100] (3) Polymyxination of chlorinated nonwoven fabrics <Example 11> Polymyxination was performed under the same conditions as in Example 9, except that 1 g of chlorinated nonwoven fabric O was used instead of 1 g of chlorinated nonwoven fabric M, to obtain polymyxin-supported nonwoven fabric O.

[0101] "Experiment 9" (1) Manufacturing of nonwoven fabrics <Manufacturing Example 24> 95 parts by mass (9.5 kg) of styrene-ethylene / butylene-styrene polymer (SEBS, Kraton Corporation, product code MD1648), containing 20% ​​by weight of styrene residues and 80% by weight of ethylene / butylene residues, was mixed with 5 parts by mass (0.5 kg) of polypropylene (Sun Allomer Corporation, product code PWH02N). Using an AIKI Riotec ALM-MB instrument, the mixture was spun and a nonwoven fabric (3000 mm long x 250 mm wide x 0.3 mm thick) was produced by the melt-blown method. This nonwoven fabric is referred to as "Nonwoven Fabric P". The chlorine content in Nonwoven Fabric P was measured by combustion ion chromatography and found to be less than 0.2 μmol / g. (2) Chlorination of nonwoven fabrics <Manufacturing Example 25> Chlorination was carried out under the same conditions as in Production Example 19, except that 1 g of nonwoven fabric P was substituted for 1 g of nonwoven fabric M, to obtain chlorinated nonwoven fabric P.

[0102] (3) Polymyxination of chlorinated nonwoven fabrics <Comparative Example 1> Polymyxination was performed under the same conditions as in Example 9, except that 1 g of chlorinated nonwoven fabric P was used instead of 1 g of chlorinated nonwoven fabric M, to obtain polymyxin-supported nonwoven fabric P. The polymyxin-supported nonwoven fabric P had strong adhesive properties between the nonwoven fabrics and could not be wound onto a blood purification column, so it could not be used for characterization.

[0103] "Experiment 10" (1) Chlorination of nonwoven fabrics In a polypropylene container, 4.84 g of the halogen compound 2-chloro-N-(hydroxymethyl)acetamide, 1.54 g of paraformaldehyde, 339 ml of nitrobenzene, and 45.2 ml of sulfuric acid were placed. 22.6 g of nonwoven fabric made of styrene-olefin copolymer (Kraton's product number MD1648: PP=9:1) was added, and the reaction was carried out in a 25°C shaking incubator at 160 rpm for 3 hours with stirring. After that, the mixture was washed three times with 200 ml of distilled water and six times with 600 ml of methanol to remove residual nitrobenzene, and then washed three more times with 500 ml of distilled water. Finally, it was dried in a constant temperature forced-air dryer at 40°C for 2 hours to obtain chlorinated nonwoven fabric Q with introduced chlorine groups.

[0104] <Example 12> (2) Tryptophanization of chlorinated nonwoven fabrics We attempted to immobilize L-tryptophan (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) on chlorinated nonwoven fabric Q using the following procedure. 45 ml of a 1 wt% tryptophan aqueous solution was placed in a polypropylene container, 300 mg of chlorinated nonwoven fabric Q and 6 mg of magnesium oxide for pH adjustment were added, and the mixture was stirred by inversion at room temperature (25°C) for 2 hours to allow the reaction to proceed. Next, the nonwoven fabric was removed, washed with hydrochloric acid and distilled water, and then dried in a forced-air dryer at 40°C for 3 hours to obtain tryptophan-introduced nonwoven fabric. The introduction of tryptophan was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the tryptophan-introduced fiber using an ATR-FT-IR (Nicolet FT-IR Thermofisher Scientific) with the tryptophan spectrum in a database, as shown in Figure 2.

[0105] "Experiment 11" <Example 13> L-arginine treatment of chlorinated nonwoven fabrics For the chlorinated nonwoven fabric Q, L( +We attempted to immobilize )-arginine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.). 45 ml of a 1 wt% arginine aqueous solution was placed in a polypropylene container, and 300 mg of chlorinated nonwoven fabric Q and 6 mg of magnesium oxide for pH adjustment were added. The mixture was stirred by inversion at around pH 9.4 at room temperature of 25°C for 2 hours to allow the reaction to proceed. Next, the nonwoven fabric was removed, washed with hydrochloric acid and distilled water, and then dried in a forced-air dryer at 40°C for 3 hours to obtain an arginine-introduced nonwoven fabric. SEM-EDS (manufactured by Hitachi High-Technologies Corporation, model number: Miniscope TM3000) measurements were performed on this nonwoven fabric, and as shown in Table 12, the introduction of N derived from arginine was confirmed. Furthermore, as shown in Figure 3, the introduction of arginine was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from chlorinated fibers from the IR spectrum obtained from arginine-introduced fibers using an ATR-FT-IR (Nicolet FT-IR Thermofisher Scientific) with the arginine spectrum in the database.

[0106] [Table 12]

[0107] "Experiment 12" <Example 14> Phenylalanination of chlorinated nonwoven fabrics The following procedure was used to attempt to immobilize phenylalanine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) on chlorinated nonwoven fabric Q. 25 ml of a 1 wt% aqueous solution of phenylalanine was placed in a polypropylene container, 1 g of chlorinated nonwoven fabric Q and 4 mg of magnesium oxide for pH adjustment were added, and the mixture was stirred by inversion at 160 rpm at 45°C for 48 hours to allow the reaction to proceed. Next, the nonwoven fabric was removed and washed three times with 30 ml of 0.1 N hydrochloric acid and three times with 50 ml of distilled water. Then, it was washed three times with 30 ml of 0.018% Triton solution, followed by suction filtration washing with 200 ml of 0.018% Triton solution and 200 ml of distilled water. Finally, it was dried in a forced-air dryer at 40°C for 2 hours to obtain the phenylalanine-immobilized nonwoven fabric. The introduction of phenylalanine was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from chlorinated fibers from the IR spectrum obtained from phenylalanine-introduced fibers using an ATR-FT-IR (Nicolet FT-IR Thermofisher Scientific) instrument, as shown in Figure 4, with the phenylalanine spectrum in a database.

[0108] "Experiment 13" <Example 15> Monoethanolamine treatment of chlorinated nonwoven fabrics The following procedure was used to attempt to immobilize monoethanolamine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) on chlorinated nonwoven fabric Q. This corresponds to the introduction of OH groups into the chlorinated nonwoven fabric. 25 ml of a 1 wt% aqueous solution of monoethanolamine was placed in a polypropylene container, 1 g of chlorinated nonwoven fabric Q and 4 mg of magnesium oxide for pH adjustment were added, and the mixture was stirred by inversion at 160 rpm at 45°C for 48 hours to allow the reaction to proceed. Next, the nonwoven fabric was removed and washed three times with 30 ml of 0.1 N hydrochloric acid and three times with 50 ml of distilled water. Then, it was washed three times with 30 ml of 0.018% Triton solution, followed by suction filtration washing with 200 ml of 0.018% Triton solution and 200 ml of distilled water. Finally, it was dried in a forced-air dryer at 40°C for 2 hours to obtain a nonwoven fabric with introduced OH groups. The introduction of the OH group was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the monoethanolamine-introduced fiber using an ATR-FT-IR (Nicolet FT-IR, Thermofisher Scientific) instrument, as shown in Figure 5, with the monoethanolamine spectrum in the database.

[0109] "Experiment 14" <Example 16> Ethylenediamine treatment of chlorinated nonwoven fabrics We attempted to immobilize ethylenediamine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) on chlorinated nonwoven fabric Q using the following procedure. This corresponds to the introduction of amino groups into chlorinated nonwoven fabric. 25 ml of 1 wt% ethylenediamine aqueous solution was placed in a polypropylene container, 1 g of chlorinated nonwoven fabric Q and 4 mg of magnesium oxide for pH adjustment were added, and the mixture was stirred by inversion at 160 rpm at 45°C for 48 hours to allow the reaction to proceed. Next, the nonwoven fabric was removed and washed three times with 30 ml of 0.1 N hydrochloric acid and three times with 50 ml of distilled water. Then, it was washed three times with 30 ml of 0.018% Triton solution, followed by suction filtration washing with 200 ml of 0.018% Triton solution and 200 ml of distilled water. Finally, it was dried in a forced-air dryer at 40°C for 2 hours to obtain an amino group-introduced nonwoven fabric. The introduction of amino groups was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from chlorinated fibers from the IR spectrum obtained from ethylenediamine-introduced fibers using an ATR-FT-IR (Nicolet FT-IR Thermofisher Scientific) as shown in Figure 6, with ethylenediamine in a database.

[0110] "Experiment 15" <Example 17> Heparinization of chlorinated nonwoven fabrics using ethylenediamine-modified fibers Heparin immobilization was attempted on the amino group-introduced nonwoven fabric obtained in Example 16 of Experiment 14, using the following procedure. 10 mg of heparin (dialdehyde heparin) treated with sodium periodate was placed in a 15 ml polypropylene container, and 10 ml of pH=4 hydrochloric acid aqueous solution was added to make a 0.1 wt% solution (approximately 200 units / ml). 100 mg of the amino group-introduced nonwoven fabric obtained in Example 16 was added to this solution. After a reaction at around pH=4 at 25°C for 24 hours (vortexing at 100 rpm), the mixture was thoroughly washed with distilled water and then dried for 3 hours in a forced-air dryer at 40°C to obtain heparin-immobilized nonwoven fabric. Regarding the introduction of heparin, as shown in Figure 7, the difference spectrum obtained by subtracting the IR spectrum obtained from the untreated fiber from the IR spectrum obtained from the heparin-introduced fiber using an ATR-FT-IR (Nicolet FT-IR Thermofisher Scientific) was compared with the FT-IR spectrum of aldehyde heparin.

[0111] "Experiment 16" <Example 18> Azidization of chlorinated nonwoven fabrics The azide group was immobilized on chlorinated nonwoven fabric Q using the following procedure. 100 mg of sodium azide was placed in a 15 ml polypropylene container, and 10 ml of distilled water was added to make a 1 wt% aqueous solution. Chlorinated nonwoven fabric Q was then placed in this solution. After a reaction at approximately pH 8 at 25°C for 24 hours (vortexing at 100 rpm), the fabric was thoroughly washed with distilled water and then dried for 3 hours in a forced-air dryer at 40°C to obtain the azide-immobilized nonwoven fabric. Regarding the introduction of the azide group, as shown in Figure 8, the obtained nonwoven fabric was subjected to ATR-FT-IR measurement in the same manner as in Experiment 14, and the introduction of the azide group was confirmed by comparing it with the spectrum of sodium azide in the database.

[0112] "Experiment 17" <Example 19> Lactoferrinization using heparinized fibers of chlorinated nonwoven fabrics Functional adsorbents were developed by immobilizing functional proteins that interact with heparin onto nonwoven fabrics via immobilized heparin. The heparin-immobilized nonwoven fabric synthesized in Example 17 of Experiment 15 not only improves blood compatibility but also interacts with many functional molecules, making it possible to use it as a base for enhancing the functionality of fibers. Heparin is known to have a strong interaction with lactoferrin. Therefore, by immobilizing lactoferrin, it is expected that it will create LPS traps, virus traps, and electrostatic interactions with LDL.

[0113] First, 100 mg of lactoferrin (derived from milk, manufactured by Fujifilm, for biochemistry, 129-04121) was dissolved in 10 ml of distilled water to prepare a 0.1 wt% lactoferrin aqueous solution (pale red). Next, 10 mg of the heparin-immobilized nonwoven fabric obtained in Example 17 was added to this lactoferrin aqueous solution, and after immersion at room temperature for 4 hours while stirring at a speed of 40 rpm, it was vigorously rinsed five times with 20 ml of distilled water at a vortex speed of approximately 300 rpm, and then dried at room temperature to obtain a lactoferrin-heparin-immobilized nonwoven fabric. Regarding the introduction of lactoferrin, as shown in Figure 9, the difference spectrum obtained by subtracting the IR spectrum obtained from the heparin-immobilized fiber from the IR spectrum obtained from the lactoferrin-immobilized fiber using an ATR-FT-IR (Nicolet FT-IR Thermofisher Scientific) was compared with the lactoferrin FT-IR spectrum.

[0114] "Experiment 18" <Example 20> Alkaline treatment and gelatinization of chlorinated nonwoven fabrics Alkali-treated gelatin was immobilized onto chlorinated nonwoven fabric Q in the following manner. Alkali-treated bovine bone gelatin (LET-N230) manufactured by Nitta Gelatin Co., Ltd. was used as the gelatin. 15 ml of an aqueous solution of 1.6 wt% alkali-treated gelatin was placed in a polypropylene container, 100 mg of chlorinated nonwoven fabric Q and 2 mg of magnesium oxide for pH adjustment were added, and the mixture was stirred by inversion at room temperature of 25°C at a pH of approximately 9.4 for 2 hours. Next, the nonwoven fabric was removed, washed with hydrochloric acid and distilled water, and then dried in a forced-air dryer at 40°C for 3 hours to obtain an alkali-treated gelatin-immobilized nonwoven fabric. SEM-EDS (Hitachi High-Technologies Corporation, model number: Miniscope TM3000) measurement of this nonwoven fabric confirmed the introduction of nitrogen derived from gelatin, as shown in Table 13. Furthermore, as shown in Figure 10, the introduction of nitrogen at the outermost surface was confirmed by measuring the change in nitrogen concentration derived from gelatin at the outermost surface using XPS (manufactured by JEOL Ltd., model number: JPS-9010MC).

[0115] [Table 13]

[0116] "Experiment 19" <Example 21> Acid treatment and gelatinization of chlorinated nonwoven fabrics Acid-treated gelatin was immobilized onto chlorinated nonwoven fabric Q in the following manner. Nitta Gelatin Co., Ltd.'s acid-treated pigskin gelatin (LET-NP250) was used. 15 ml of a 1.6 wt% acid-treated gelatin aqueous solution was placed in a polypropylene container, and 100 mg of chlorinated nonwoven fabric Q and 2 mg of magnesium oxide for pH adjustment were added. The mixture was then stirred by inversion at approximately pH 9.4 at room temperature (25°C) for 2 hours. Next, the nonwoven fabric was removed, washed with hydrochloric acid and distilled water, and then dried in a forced-air dryer at 40°C for 3 hours to obtain an acid-treated gelatin-immobilized nonwoven fabric. SEM-EDS (Hitachi High-Technologies Corporation, model: Miniscope TM3000) measurements of this nonwoven fabric confirmed the introduction of nitrogen derived from gelatin, as shown in Table 14. Furthermore, as shown in Figure 11, the introduction of nitrogen at the outermost surface was confirmed by measuring the change in nitrogen concentration derived from gelatin at the outermost surface using XPS (manufactured by JEOL Ltd., model number: JPS-9010MC).

[0117] [Table 14]

[0118] "Characteristic Evaluation 3" The properties of various ligand-supported nonwoven fabrics from Examples 9 to 21 were evaluated. Toray Industries, Inc.'s "Toremixin PMX-20R" was used as a comparative material. In Characteristic Evaluation 3, the conditions were the same as in Characteristic Evaluation 1 unless otherwise specified.

[0119] (1) Fine particle measurement Tables 15 and 16 show a comparison of the number of fine particles generated when various ligand-supported nonwoven fabrics and a comparison material were subjected to two types of treatment. The treatment and measurement methods of the measured materials were the same as in Characterization 2. The results for samples that were inverted and stirred in a rotator are shown in Table 15, and the results for samples that were ultrasonically cleaned are shown in Table 16. As is clear from Tables 15 and 16, in both treatment cases, the samples of each example were found to generate less fine particles compared to the comparison material.

[0120] [Table 15]

[0121] [Table 16] (2) Chlorine content Table 17 shows a comparison of the chlorine content of polymyxin-supported nonwoven fabrics M, N, O and the comparison material after autoclaving. The chlorine content was measured by combustion ion chromatography. As is clear from Table 17, each sample from Examples 9 to 11 was found to contain a lower chlorine content than the comparison material.

[0122] [Table 17]

[0123] (3) Change in pH after autoclaving Table 18 shows the pH change of physiological saline before and after autoclaving various ligand-supported nonwoven fabrics and a comparative material in physiological saline. The treatment and measurement conditions of the measured materials were the same as in Characterization 2. From these results, the pH change of the samples in each example was smaller compared to the comparative material. Therefore, it was suggested that the rinsing process before use could be significantly simplified for the samples in each example.

[0124] [Table 18]

[0125] (4) Adsorption capacity of endotoxins in water Table 19 shows the results of an adsorption treatment in which 5 mg each of various ligand-supported nonwoven fabrics and comparative materials, after autoclaving, were immersed in 4 ml of deionized water prepared to an endotoxin concentration of 100 EU / mL, and the amount of adsorption was measured after 2 hours while stirring at 37°C and 10 rpm. The adsorption rate (%) in the table is the value obtained by multiplying (blank concentration - measured concentration) / blank concentration by 100.

[0126] [Table 19]

[0127] Nonwoven fabrics into which amino acids were introduced as ligands showed a clear indication of the endotoxin adsorption mechanism. Nonwoven fabrics immobilized with tryptophan, which has both a hydrophobic portion and an amino group after immobilization, showed a relatively high endotoxin adsorption rate of approximately 60%. Considering these results, it is presumed that endotoxin adsorption does not occur solely due to charging, but involves multiple factors derived from the structure and chemical composition of the ligand, with factors such as the distance between the charged portion and the hydrophobic portion having a significant impact on the strength of the interaction. It was also found that nonwoven fabrics made from low-molecular-weight compounds such as ethylenediamine and monoethanolamine, converted into amino groups and OH groups, could adsorb endotoxin with high efficiency of 97% and 98%, respectively. This is thought to be because, since the introduced ligand is an extremely small molecule, the hydrophobicity of the base fiber developed in this invention and the charge of the introduced ligand are in close proximity, enabling more efficient removal. This makes it possible to apply this to filters that remove bio-harmful substances from water at low cost.

[0128] It is also possible to introduce ligands such as polysaccharides and glycoproteins. As an example, the endotoxin removal ability of heparin-immobilized nonwoven fabric and nonwoven fabric immobilized with lactoferrin, which is known to have a strong interaction with heparin, was compared. Heparin has strong anticoagulant activity and offers a significant advantage in removing harmful substances from the blood by increasing blood compatibility. However, it has a negative charge and causes electrostatic repulsion with the negative charge of endotoxins, resulting in only a small removal rate of 18%. On the other hand, nonwoven fabric immobilized with lactoferrin, which is known to have a strong interaction with LPS and is immobilized by a strong interaction with heparin and is known to be positively charged under physiological conditions, was confirmed to remove endotoxins with a high efficiency of 91%. This suggests that a nonwoven fabric can be created that maintains heparin-based blood compatibility while removing endotoxins and lipids from the blood through the strong interaction of lactoferrin bound to free iron in the blood.

[0129] Regarding gelatin, a protein known for its interactions with cell adhesion scaffolds and MMPs, endotoxin adsorption experiments were conducted on nonwoven fabrics immobilized with gelatin produced by two different processing methods. In the case of nonwoven fabric immobilized with alkali-treated gelatin, the isoelectric point of the immobilized alkali-treated bovine bone gelatin is approximately around pH=5, and it becomes negatively charged in the neutral region of pH=7.4. Therefore, in an adsorption experiment of negatively charged LPS in water, the removal rate was only about 38.5% after 2 hours, but some LPS was removed due to the effects of hydrophobic interactions, etc. It is thought that it may be effective in adsorbing positively charged LDL, etc., around pH=7.4. On the other hand, in the case of nonwoven fabric immobilized with acid-treated gelatin, the isoelectric point of the immobilized porcine dentric acid-treated gelatin is approximately around pH=8~9, close to the raw material collagen, and it becomes positively charged in the neutral region of pH=7.4. Therefore, in adsorption experiments of negatively charged LPS in water, the effectiveness was confirmed, showing a removal rate of approximately 98% after 2 hours. Overall, ligands with a positive charge and a hydrophobic portion showed high removal efficiency as ligands for adsorbing LPS.

[0130] (5) Adsorption capacity of proteins, lipids, and iron in normal serum The ligand-supported nonwoven fabrics used in the test were the following eight types of nonwoven fabrics. Polymyxin-immobilized nonwoven fabric (Example 2) PMx 10.4 mg Tryptophan-immobilized nonwoven fabric (Example 12) TPF 10.3 mg Arginine-immobilized nonwoven fabric (Example 13) ALG 10.6 mg Phenylalanine-immobilized nonwoven fabric (Example 14) PHA 10.1 mg Aminoethyl-immobilized nonwoven fabric (Example 16) EDA 9.8 mg Heparin-immobilized nonwoven fabric (Example 17) HEP 9.9 mg Heparin-lactoferrin immobilized nonwoven fabric (Example 19) HEP-LF 10.2 mg Acid-treated gelatin-immobilized nonwoven fabric (Example 21) ATG 10.7 mg

[0131] Approximately 10 mg of each finely chopped sample was added to a 5 ml glass tube and primed with heparinized saline to thoroughly wet the tubes. Immediately before the experiment, the priming solution was removed using a pipette, and 2 ml of porcine serum was added at 37°C. Specifically, the serum was collected by adding calcium chloride to blood to activate the coagulation system, centrifuging at 1200 G after 30 minutes, and then collecting the serum. At this point, 0.5 ml of untreated serum was collected in a control tube to be used as the control serum for the test. Subsequently, 2 ml of serum was dispensed into test tubes for the eight types of samples mentioned above, and the adsorption experiment was performed using a shaking shaker (Bio-Rad) heated to 37°C at a shaking speed of 350 rpm. Sampling was performed 2 hours after the start of the adsorption experiment to obtain the serum test samples. The test items were total protein, albumin, iron, total cholesterol, free cholesterol, esterified cholesterol, triglycerides, LDL, and HDL. The test results are shown in Table 20. Adsorption experiments showed that nonwoven fabrics using heparin-lactoferrin, tryptophan, and acid-treated gelatin as ligands adsorbed lipids such as total cholesterol, free cholesterol, esterified cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol.

[0132] [Table 20]

[0133] (6) Adsorption capacity of bilirubin and bile acids in normal serum The tests used the same eight nonwoven fabrics as those used to examine the protein, lipid, and iron adsorption capacity of normal serum in (5) above. The control serum and serum test samples were also prepared under the same conditions as those used for the protein, lipid, and iron adsorption capacity of normal serum in (5) above. The test items included total bilirubin, direct bilirubin, indirect bilirubin, and total bile acid levels. The test results are shown in Table 21.

[0134] Bilirubin is released into the bloodstream when severe liver damage occurs and is a causative agent of hepatic coma; removal therapy using ion exchange resins and activated bilirubin is performed. As shown in Table 21, it was confirmed that tryptophan, lactoferrin, and acid-treated gelatin, which have positive charge and hydrophobicity, can remove approximately 8% of bilirubin. Bilirubin is a negatively charged molecule, and it was confirmed that a nonwoven fabric into which arginine ligand, the most basic amino acid, has been introduced has the ability to adsorb 33% of total bilirubin and almost 100% of indirect bilirubin, indicating that it can be a useful adsorbent.

[0135] [Table 21] [Industrial applicability]

[0136] This invention can be used for blood purification, the purification of pharmaceuticals and their raw material liquids, and wastewater treatment.

Claims

1. A nonwoven fabric base material used in liquid purification fiber materials for removing bio-harmful substances from liquids, which contains a mixed resin of polypropylene and styrene-olefin copolymer within a single fiber, The mass ratio of polypropylene to the total mass in the mixed resin is 10% by mass or more and 80% by mass or less. A nonwoven fabric substrate characterized in that the mass ratio of total styrene residues to the mass of the styrene-olefin copolymer is 5% by mass or more and 50% by mass or less.

2. The nonwoven fabric base material according to claim 1, characterized in that the mass ratio of polypropylene to the mass in the mixed resin is 20% by mass or more and 50% by mass or less.

3. A fibrous material for liquid purification using a nonwoven fabric base material according to claim 1 or 2, A substituent containing a halogen group is introduced as a spacer in the styrene-olefin copolymer. Some of the halogen groups in the spacer are substituted with ligands that interact with biotoxic substances. A liquid purification fiber material characterized in that the halogen content in the liquid purification fiber material is greater than 0 μmol / g and less than or equal to 900 μmol / g relative to the mass of the liquid purification fiber material.

4. The liquid purification fiber material according to claim 3, characterized in that the halogen content in the liquid purification fiber material is greater than 0 μmol / g and 290 μmol / g or less relative to the mass of the liquid purification fiber material.

5. The ligand is derived from amino acids, oligopeptides, peptides, sugars, oligopolysaccharides, antibodies, lipopolysaccharides, lipids, proteoglycans, proteins, aptamers, and / or polymer electrolytes that interact with biotoxic substances. It has one or more nucleophilic substituents, The liquid purification fiber material according to claim 3, characterized in that it is supported on a styrene-olefin copolymer by chemical bonding between the nucleophilic substituent and the spacer.

6. A method for producing a liquid purification fiber material according to claim 3, A halogenation step is to bring a halogen compound into contact with the nonwoven fabric substrate to obtain a halogenated nonwoven fabric. A ligand loading step is performed by dehalogenating the halogenated nonwoven fabric and supporting the ligand on the styrene-olefin copolymer. A method for producing a fibrous material for liquid purification that includes [the specified material].

7. The method for producing a fiber material for liquid purification according to claim 6, wherein the ligand is a polymyxin.

8. A cleaning device comprising the liquid purification fiber material described in claim 3 inside.

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