Nonwoven fabric substrate, liquid purifying fiber material, method for manufacturing the material, and purifier provided with the material

Abstract

This invention provides an inexpensive, low-maintenance, and particulate-suppressing fiber material for liquid purification, as well as a cleaner equipped with the same. The invention relates to a nonwoven fabric substrate, a fiber material for liquid purification using the nonwoven fabric substrate, a method for manufacturing the material, and a cleaner equipped with the material. The nonwoven fabric substrate is used in the fiber material for liquid purification, which is used to remove harmful substances from liquids. The nonwoven fabric substrate contains a mixed resin of polyolefin and styrene-olefin copolymer within a single fiber. The mass ratio of polyolefin to the mixed resin is 10% by mass or more and 80% by mass or less, and the mass ratio of all styrene residues to the styrene-olefin copolymer is 5% by mass or more and 50% by mass or less.

Description

[0001] This application is a divisional application of Chinese Patent Application No. 202280052446.1, filed on July 27, 2022, entitled "Non-woven fabric substrate, fiber material for liquid purification, method of manufacturing the material and cleaner equipped with the material".

[0002] Cross-reference This application claims priority based on Japanese Patent Application No. 2021-123959, filed on July 29, 2021, the contents of which are incorporated herein by reference. Furthermore, the contents of other patents, patent applications, and documents cited in this application are incorporated herein by reference. Technical Field

[0003] This invention relates to a nonwoven fabric substrate, a liquid purification fiber material using a nonwoven fabric substrate, a method for manufacturing the liquid purification fiber material, and a cleaner equipped with the liquid purification fiber material. Background Technology

[0004] To mitigate the risks associated with the processes of removing and purifying contaminants from medical devices and pharmaceutical solutions, as well as the biological reactions caused by the resulting harmful substances, columnar adsorption devices have been developed. These devices remove pathogens by refluxing the target liquid within an adsorption carrier, achieving significant success both industrially and clinically. However, recent outbreaks, such as COVID-19, have highlighted the issue of viral and biological contamination spreading into the environment, necessitating the development of new, highly functional adsorption carriers for purification. For instance, while blood purification therapies are implemented in the medical field for the prevention and treatment of various immune diseases and sepsis, the development of adsorption-type blood purifiers with built-in adsorption carriers that offer good blood compatibility and high selectivity for pathogens is still underway.

[0005] Examples of adsorbents used in blood purification include, for instance, Patent Document 1 (Japanese Patent Application Laid-Open No. 2019-136499), which discloses an adsorbent used as a removal material for activated leukocyte-platelet complexes contained in blood. This adsorbent comprises a water-insoluble carrier containing a ligand and a substrate. The ligand has a structure in which a hydrocarbon group, which can be substituted by a substituent selected from the group consisting of halogen atoms, hydroxyl groups, ketone groups, ether groups, and ester groups, is bonded to a carbon atom of a secondary amide. Here, "ligand" refers to a chemical substance or chemical structure used to impart adsorption properties, and "substrate" refers to a material capable of interacting with the ligand.

[0006] Furthermore, Patent Document 2 (WO 2019 / 049961 A1) discloses an immunosuppressive protein adsorbent material and adsorption column, using a polymer alloy (mixture) of polystyrene and polypropylene bonded together with one or more nitrogen-containing compounds, including polyamines and aliphatic amines represented by specific formulas. More specifically, the carrier is a knitted fabric formed from a sea-island structure of fibers, which is formed by multiple fibers formed of polypropylene surrounding the polymer alloy of polystyrene and polypropylene, and is believed to maintain physical strength due to this structure. In practice, in the embodiments, according to the vibration test method for packaged goods and containers (JIS Z 0232), the number of particles inside the column was low after one hour of vibration in both horizontal and vertical directions, indicating suitability for medical use.

[0007] Furthermore, extensive research has been conducted on knitted fabrics made of polymer alloy fibers having the aforementioned island structure, as shown in Patent Documents 3-10. For example, Patent Document 3 (Japanese Patent Application Publication No. 5-71603) and Patent Document 4 (Japanese Patent Application Publication No. 1-279908) demonstrate its application as a bilirubin adsorbent; Patent Document 5 (Japanese Patent Application Publication No. 11-104236) showcases the adsorption properties of island-shaped fibers immobilized with polymyxin B that activate macrophages; Patent Document 6 (Japanese Patent Application Publication No. 6-22623) presents an endotoxin adsorbent material with low heparin adsorption capacity; Patent Document 7 (Japanese Patent Application Publication No. 60-5166) and Patent Document 8 (Japanese Patent Application Publication No. 5-329207) demonstrate the endotoxin removal performance of island-shaped fibers immobilized with polymyxin; Patent Document 9 (Japanese Patent Application Publication No. 60-209525) exhibits endotoxin decomposition properties; and Patent Document 10 (Japanese Patent No. 3817808) imparts adsorption properties for enterotoxins in addition to endotoxins. These patent documents demonstrate the wide applicability of this fiber as an adsorbent material carrier.

[0008] Furthermore, the polymer materials constituting the island-shaped fiber are detailed in Patent Document 1, for example.

[0009] (The following is quoted): "The material for removing the activated leukocyte-activated platelet complex includes a water-insoluble carrier containing a ligand and a substrate, wherein the ligand is..."; "As a substrate, for example, it is a polymeric material containing functional groups such as aromatic rings and hydroxyl groups that are reactive with carbocations in a repeating structure, such as poly(aromatic vinyl compounds) (e.g., polystyrene), polyesters (e.g., polyethylene terephthalate, polybutylene terephthalate), polysulfone, polyethersulfone, polyvinyl alcohol, etc., synthetic polymeric materials, cellulose, collagen, chitin, chitosan, dextran, etc., and further, it can be a derivative of the above-mentioned synthetic polymeric material or the above-mentioned natural polymeric material endowed with alkyl, halogen atoms, haloalkyl, acetal, ether groups, etc., for example, if it is a polystyrene derivative, examples include poly(p-chloromethylstyrene), poly(phenylene terephthalate ... α -Methylstyrene, poly β 1-Methylstyrene, poly(p-tert-butoxystyrene), poly(p-acetoxystyrene), and poly(1-ethoxystyrene). The composition of these polymeric materials is not particularly limited; homopolymers, copolymers using monomers of various of the above-mentioned polymeric materials, or physical blends of various of the above-mentioned polymeric materials can be used. Particularly in materials for removing activated leukocyte-activated platelet complexes, poly(aromatic vinyl compounds) (e.g., polystyrene) or derivatives thereof, polyesters (e.g., polyethylene terephthalate, polybutylene terephthalate) or derivatives thereof, polysulfones or derivatives thereof, or polyethersulfones or derivatives thereof are preferred; more preferably, polystyrene or polysulfones or derivatives thereof, i.e., polystyrene or derivatives thereof or polysulfones or derivatives thereof. Polystyrene or derivatives thereof are further preferred from the perspective of a large number of aromatic rings per unit weight and ease of ligand introduction. Furthermore, the material used in the substrate may contain a cross-linked structure. There are no limitations on the crosslinking structure. For example, materials that have been crosslinked by copolymerizing difunctional monomers such as divinylbenzene, or materials that have been crosslinked by reacting a crosslinking agent such as an aldehyde with functional groups such as aromatic rings and hydroxyl groups in the material, are preferred from the perspective of ease of procurement. Materials that have been crosslinked by reacting a difunctional compound with functional groups such as aromatic rings and hydroxyl groups in the material are even more preferred. Formaldehyde is even more preferred as a crosslinking agent. (End of quote)

[0010] Furthermore, Patent Document 11 (Japanese Patent Application Publication No. 2003-511354) discloses an endotoxin adsorbent material in which oligopeptides exhibiting polydispersity are immobilized on porous microspheres such as ToyoPearl HW70EC; Patent Document 12 (Japanese Patent Application Publication No. 2012-515577) discloses a method of hydrophobically coating particles with a diameter of 5 mm with polymyxin. mEndotoxin adsorbent material is made of porous particles of polystyrene-divinylbenzene copolymer with a diameter of about m; Patent Document 13 (Japanese Patent Application Publication No. 4-270965) discloses an LPS (endotoxin) adsorbent carrier in which oligopeptides such as polymyxin B are hydrophobically bound to the surface of a membrane or sheet of polystyrene, or a cloth (woven or non-woven) of polyester or polypropylene; Patent Document 14 (Japanese Patent Application Publication No. 2016-137099) discloses a blood purifier with a soft container, which contains a porous solid filament mainly composed of cellulose, polymethyl methacrylate, etc., which are aligned in one direction.

[0011] Furthermore, Patent Document 15 (Japanese Patent No. 3533541) describes a nonwoven fabric that can be used as a filter for selecting cells. This nonwoven fabric comprises synthetic polymers 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 polymers. Additionally, it describes that, from the perspective of mechanical strength and surface area, an effective filter has a fiber diameter of 1... m m or more and 100 m Below m.

[0012] Existing technical documents Patent documents Patent Document 1: Japanese Patent Application Publication No. 2019-136499 Patent Document 2: WO2019 / 049961A1 Patent Document 3: Japanese Patent Publication No. 5-71603 Patent Document 4: Japanese Patent Application Publication No. 1-279908 Patent Document 5: Japanese Patent Application Publication No. 11-104236 Patent Document 6: Japanese Patent Publication No. 6-22623 Patent Document 7: Japanese Patent Application Publication No. 60-5166 Patent Document 8: Japanese Patent Application Publication No. 5-329207 Patent Document 9: Japanese Patent Application Publication No. 60-209525 Patent Document 10: Japanese Patent No. 3817808 Patent Document 11: Japanese Patent Publication No. 2003-511354 Patent Document 12: Japanese Patent Application Publication No. 2012-515577 Patent Document 13: Japanese Patent Application Publication No. 4-270965 Patent Document 14: Japanese Patent Application Publication No. 2016-137099 Patent Document 15: Japanese Patent No. 3533541 Summary of the Invention The technical problem that the invention aims to solve However, the aforementioned known adsorption materials have technical problems that need to be solved.

[0013] Patent document 1 investigates the ligand dissociation under 24-hour immersion in water at 50°C by pH change, but does not address the pH after autoclaving (121°C, 20 minutes), which is important in actual use.

[0014] While Patent Document 2 assesses the durability against vibrations during transport, it does not address any issues regarding the strength and fragility of the carrier itself, which are problematic in actual manufacturing and reaction processes.

[0015] Patent documents 3-10 disclose various adsorbents using island-shaped fibers. Regarding the polymer raw materials used as materials for these fibers, the following information is disclosed: (1) "There are no particular restrictions on the composition of these polymer materials. Homopolymers, copolymers of monomers of various polymer materials, or physical blends of various polymer materials can be used." (2) Among them, from the perspective of having a large number of aromatic rings per unit weight and being easy to introduce ligands, polystyrene or its derivatives are further preferred.

[0016] (3) It may also contain cross-linked structures.

[0017] However, there is currently no approach that addresses the inherent fragility of the fiber itself (such as the generation of problematic particles due to manufacturing processes, transportation processes, and usage conditions). If one had to categorize it, one could say that current methods focus on increasing strength through cross-linking. Furthermore, the reason for choosing polystyrene or its derivatives as the most suitable material is the number of aromatic rings per unit weight; the high amount of ligands incorporated is the basis of the design. That is, materials with structures incorporating as many ligands as possible are important; for example, there are no examples of explicitly limiting the amount of aromatic rings in the material itself to improve fiber fragility. Additionally, regarding island-type fibers, achieving their intricate structures requires specialized manufacturing equipment, thus posing a practical problem of high manufacturing costs.

[0018] Patent documents 11-14 disclose shapes such as beads, films, nonwoven fabrics, and solid filaments as substrates or carriers, and list various polymer materials as substrates. However, they do not conduct specific research on the strength, fragility, and sterilization resistance of the substrates themselves. Example 15 also describes the use of various polymer materials, copolymers, and block copolymers as substrates, but the example only uses "nonwoven fabric containing polystyrene." For example, it does not take into account the test results regarding the fragility of the fibers (the generation of microparticles) or the material selection ideas regarding steam sterilization resistance.

[0019] As mentioned above, previous research and development of adsorbents has focused on adsorption performance, especially selectivity. However, there is room for improvement in aspects such as the processability of the substrate materials themselves in the manufacturing process (e.g., durability, robustness (low particle generation)), and the sterilization resistance of products that become problematic during use. The processability of the substrate materials themselves in the aforementioned manufacturing processes becomes important when manufacturing water treatment devices, medical adsorbers, etc. Furthermore, there is a demand for further reductions in manufacturing costs.

[0020] More specifically, the technical problem to be solved is the inconvenience of prolonged cleaning before use if the sterilization resistance is poor. Most of the aforementioned known adsorbent materials contain a large number of styrene units as reaction sites on the substrate fibers. Therefore, the amount of chloromethyl compounds introduced as reaction intermediates also increases. As a result, the amount of residual chlorine groups that do not react with activity-inducing compounds (such as polymyxin) also increases. If a large number of chlorine groups are present, hydrochloric acid will be released from the storage solution over time due to surface hydrolysis during long-term storage. In fact, if commercially available blood purification fiber materials are autoclaved in physiological saline, the chlorine groups will be released, resulting in an acidic pH of around 2. In clinical use, prior cleaning with large amounts of physiological saline is necessary, which is inconvenient for users.

[0021] Furthermore, increasing the amount of chloromethyl compounds introduced would excessively consume the expensive, immobilized active derivative compounds. To control costs, reducing the concentration of active derivative compounds during the immobilization reaction has been considered. However, in active derivative compounds with multiple free amino groups that act as active sites within the molecules, there are concerns that amino groups interacting with endotoxins might be consumed during the immobilization reaction, resulting in a decrease in the number of free amino groups and thus a reduction in interactions with endotoxins. Therefore, a high concentration of active derivative compounds is required during the immobilization reaction, leading to an increase in the cost of the final liquid purification fiber material.

[0022] Furthermore, if the substrate is fragile, a large number of particles will be generated during the reaction processing and filling to the final form in the manufacturing process. Removing these particles requires a significant amount of water and labor. In particular, polystyrene is more brittle than polyolefins, so the outermost layer of polystyrene is at high risk of peeling off under stress, making it prone to particle generation. In cases of use in living organisms, as specified in pharmacopoeias, the entry of particles into the organism is extremely strictly limited. Moreover, based on recent issues such as marine microplastics, it is necessary to vigorously suppress the risk of particles being released into the environment.

[0023] The purpose of this invention is to solve the above-mentioned technical problems, namely, to provide a cheap, low-cost fiber material for liquid purification that reduces cleaning and suppresses the generation of particulate matter, and a cleaner equipped with the same.

[0024] Technical solutions for solving technical problems The inventors conducted in-depth research on improvements in these aspects and surprisingly discovered that by using styrene-based block copolymers, an adsorption substrate can be provided inexpensively, thus completing the present invention. Compared with conventional substrates using polystyrene, this adsorption substrate exhibits high adsorption performance despite having a lower content of styrene residues per unit weight, and produces very few particles (firmly) and has steam sterilization resistance. Specifically, as described below.

[0025] (1) In one embodiment for achieving the above objective, the nonwoven fabric substrate is, A nonwoven fabric substrate is disclosed as a fiber material for liquid purification, the fiber material being used to remove harmful substances from liquids. The nonwoven fabric substrate comprises a mixed resin of polyolefin and styrene-olefin copolymer within a single fiber. The mass ratio of the polyolefin to the above-mentioned mixed resin is 10% by mass or more and 80% by mass or less. The mass ratio of all styrene residues to the mass of the above-mentioned styrene-olefin copolymer is more than 5% by mass and less than 50% by mass.

[0026] (2) In another embodiment of the nonwoven fabric substrate, the mass ratio of polyolefin to the above-mentioned mixed resin is preferably 20% by mass or more and 50% by mass or less.

[0027] (3) In another embodiment of the nonwoven fabric substrate, it is preferred that the above-mentioned styrene-olefin copolymer may also be at least one copolymer selected from the group consisting of a saturated copolymer formed by polymerizing an aromatic vinyl compound with an olefin having one double bond, an unsaturated copolymer formed by polymerizing an aromatic vinyl compound with a diene having two conjugated double bonds, and a hydrogenated saturated copolymer obtained by hydrogenating the above-mentioned unsaturated copolymer.

[0028] (4) In one embodiment for achieving the above objective, the liquid purification fiber material is a liquid purification fiber material using any of the above-mentioned nonwoven fabric substrates. The above-mentioned styrene-olefin copolymer incorporates substituents containing halogen groups as spacer groups. Some of the halogen groups in the aforementioned spacer groups are replaced by ligands that interact with substances harmful to organisms. The halogen content in the aforementioned fiber material for liquid purification is greater than 0 relative to the mass of the aforementioned fiber material for liquid purification. m mol / g and 900 m Below mol / g.

[0029] (5) In another embodiment of the fiber material for liquid purification, it is preferable that the halogen content in the fiber material for liquid purification is greater than 0 relative to the mass of the fiber material for liquid purification. m mol / g and 290 m Below mol / g.

[0030] (6) In another embodiment of the fibrous material for liquid purification, the above-mentioned ligand is preferred: Derived from amino acids, oligopeptides, peptides, sugars, oligosaccharides, antibodies, lipopolysaccharides, lipids, proteoglycans, proteins, aptamers, and / or high molecular weight electrolytes that interact with harmful substances in organisms. Having more than one nucleophilic substituent, Styrene-olefin copolymers can be supported by chemical bonding of the above-mentioned nucleophilic substituents with the above-mentioned spacer groups.

[0031] (7) A method for manufacturing a liquid purification fiber material according to one embodiment for achieving the above-mentioned objective is a method for manufacturing any of the above-mentioned liquid purification fiber materials, comprising: The halogenation process involves contacting a halogen compound with the aforementioned nonwoven fabric substrate to obtain a halogenated nonwoven fabric; and In the ligand loading process, the halogenated nonwoven fabric is dehalogenated to load the ligand onto the styrene-olefin copolymer.

[0032] (8) In another embodiment of the method for manufacturing a fiber material for liquid purification, it is preferable that the ligand is a polymyxin.

[0033] (9) The cleaner according to one embodiment for achieving the above objective has any of the above-described liquid purification fiber materials inside.

[0034] Invention Effects According to the present invention, a fibrous material for liquid purification that reduces cleaning and suppresses particulate generation, and a cleaner having the same, can be provided at low cost. Attached Figure Description

[0035] Figure 1 A longitudinal cross-sectional view of the cleaner according to an embodiment of the present invention is shown.

[0036] Figure 2 The differential spectrum of tryptophan-immobilized fibers is shown.

[0037] Figure 3 The differential spectrum of arginine-immobilized fibers is shown.

[0038] Figure 4 The differential spectrum of phenylalanine-immobilized fibers is shown.

[0039] Figure 5 The differential spectrum of monoethanolamine-immobilized fibers is shown.

[0040] Figure 6 The differential spectrum of ethylenediamine-immobilized fibers is shown.

[0041] Figure 7 The differential spectrum of heparin-immobilized fibers is shown.

[0042] Figure 8 The differential spectrum of the azide-based immobilized fiber is shown.

[0043] Figure 9 The differential spectrum of lactoferrin-heparin immobilized fibers is shown.

[0044] Figure 10 The XPS measurement results from Experiment 19 are shown.

[0045] Figure 11 The XPS measurement results from Experiment 20 are shown.

[0046] Explanation of reference numerals in the attached figures 1: Container body 2: Bottom 3: Pipe 4: Contact surface 5: Outlet 6: Opening 7: Inlet 8: Divider 9: Stopping component 10: Through hole 11: Inner bottom surface 12: Ligand-immobilized nonwoven fabric 13: Filter 100: Washer Detailed Implementation Next, embodiments of the present invention will be described. It should be noted that the embodiments described below do not limit the invention to the scope of the claims, and that not all of the elements and combinations thereof described in the embodiments are necessarily necessary for the solution of the present invention.

[0047] <Non-woven fabric substrate> The nonwoven fabric substrate according to embodiments of the present invention is a liquid purification fiber material used for adsorbing and recovering harmful substances from biological organisms from solutions (e.g., blood, plasma, serum, pharmaceuticals, cell culture media, water, etc.). This nonwoven fabric substrate comprises a melt-mixed resin of a polyolefin and a styrene-olefin copolymer, and is formed into a nonwoven fabric by incorporating the polyolefin and styrene-olefin copolymer within a single fiber. The nonwoven fabric substrate, for example, has a sheet-like form. There are no particular limitations on the planar area of ​​the nonwoven fabric substrate. The thickness of the nonwoven fabric substrate is, for example, 20 mm. m m or more and 3000 m Below m.

[0048] The blended fibers of polyolefin and styrene-olefin copolymer are preferably 50 nm or more in average diameter and 500 nm. m m or less, more preferably an average diameter of 80 nm or more and 40 m m or less, more preferably an average diameter of 100 nm or more and 30 m Fibers with an average length of 5 mm or less. Furthermore, the blended fibers are preferably fibers with an average length of 5 mm or more, more preferably 10 mm or more, and even more preferably 20 mm or more. In this application, "average diameter" refers to the value obtained by averaging the 100 diameters obtained by randomly observing the cross-sections of the fibers in 100 fields of view using a scanning electron microscope, a transmission electron microscope, or a digital microscope, converting each cross-section into a circle. Similarly, "average length" refers to the value obtained by averaging the 100 lengths obtained by randomly observing the side surfaces of the fibers in 100 fields of view using an optical microscope, calculating the length of each fiber when laid straight. The same applies to "average diameter" and "average length" as used below.

[0049] A styrene-olefin copolymer is a polymer of two or more styrene monomers and two or more olefin monomers. It can be any type of copolymer selected from block copolymers, random copolymers, alternating copolymers, and graft copolymers, with block copolymers being preferred. The styrene-olefin copolymer is preferably at least one copolymer selected from the group consisting of a saturated copolymer of an aromatic vinyl compound and an olefin having one double bond, an unsaturated copolymer of an aromatic vinyl compound and a diene having two conjugated double bonds, and a hydrogenated saturated copolymer obtained by hydrogenating an unsaturated copolymer.

[0050] The polystyrene blocks constituting the styrene-olefin block copolymer become physical crosslinking points below the glass transition temperature, exhibiting excellent rubber elasticity. Furthermore, the polyolefin blocks constituting the styrene-olefin block copolymer possess fluidity above the glass transition temperature, contributing to easy processability. Examples of preferred styrene-olefin block copolymers include diblock copolymers having a PS-PO configuration and triblock copolymers having a PS-PO-PS configuration. Here, "PS" refers to polystyrene, and "PO" refers to polyolefin. Examples of preferred styrene-olefin copolymers include hydrogenated styrene-olefin copolymers, more preferably at least one copolymer selected from the group consisting of styrene-ethylene / butene-styrene block copolymers (hereinafter sometimes simply referred to as "SEBS"), styrene-ethylene / propylene-styrene block copolymers (hereinafter sometimes simply referred to as "SEPS"), and styrene-(ethylene-ethylene / propylene)-styrene block copolymers (hereinafter sometimes simply referred to as "SEEPS"), with SEBS being even more preferred.

[0051] The mass percentage of polyolefin in the blended fiber 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. If styrene-olefin copolymers are melt-spun using their monomers, more filament breakage occurs; however, by melt-blending polyolefins, spinnability can be improved.

[0052] The mass ratio of all styrene residues to 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 or less, 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. If the mass ratio of all styrene residues to the styrene-olefin copolymer is set to 5% by mass or more and 50% by mass or less, the number of benzene rings that are introduced as halogen groups is limited, thus suppressing the amount of halogen groups. Furthermore, by suppressing the brittleness of the nonwoven fabric, the amount of particulate matter generated can be further reduced. In addition, even with a reduced amount of halogen groups, ligands for adsorbing harmful substances (in one example, endotoxins) from organisms can be adequately introduced, thus reducing the amount of ligands required in the manufacture of the liquid purification fiber material, thereby achieving cost reduction of the liquid purification fiber material. Here, "halogen" is interpreted as meaning that the ligand-immobilized nonwoven fabric (liquid purification nonwoven fabric) made by mixing a nonwoven fabric substrate containing a polymer that originally contains halogens does not contain the halogens in that polymer. It should be noted that harmful substances to organisms, in addition to endotoxins, also include enterotoxins, bilirubin, abnormal cells such as cancer cells and white blood cells in the blood, immunogenic substances, excessive essential elements, proteins, lipids, bile acids, viruses, bacteria and their spores, endocrine disruptors, heavy metals (including iron), and substances that are pathogenic to Alzheimer's disease. β Pathogenic substances for various diseases, such as amyloid protein.

[0053] <Manufacturing Method of Nonwoven Fabric Substrate> Nonwoven substrates can be manufactured by any method that allows the blending of polyolefin and styrene-olefin copolymer fibers to form a nonwoven substrate. More preferred manufacturing methods are melt-blowing, needle punching, and electrospinning. The following describes each of these manufacturing methods.

[0054] (1) Meltblown method Polyolefins and styrene-olefin copolymers are melt-blended and flowed through a blower with micropores into a roller using air power. This produces a nonwoven fabric containing fibers incorporating the polyolefin and styrene-olefin copolymer within a single fiber. Since no adhesive is used, a nonwoven fabric composed solely of fibers mixed with the resin can be obtained.

[0055] (2) Acupuncture Nonwoven fabric is produced by thinly overlapping multiple layers of fibers containing a mixture of polyolefins and styrene-olefin copolymers and compressing them using a machine with needles. This method utilizes needles to pull the fibers together, causing them to intertwine.

[0056] (3) Electrospinning This method is also known as electrospinning. The spinning device has a DC high-voltage power supply, a spinning nozzle, and a collector. Polyolefins and styrene-olefin copolymers are melt-mixed, and the polymer solution is extruded from the high-voltage spinning nozzle. The extruded polymer solutions become fibers with nanoscale fiber diameters, which reach the grounded collector to form a nonwoven fabric.

[0057] It should be noted that the nonwoven fabric substrate involved in this embodiment can be manufactured using methods other than those described above, such as air-laid method, spunbond method, wet method similar to papermaking, etc.

[0058] <Fiber Materials for Liquid Purification> The liquid purification fiber material involved in this embodiment is a material in which ligands that interact with substances harmful to living organisms are introduced into the aforementioned nonwoven fabric substrate. Specifically, this liquid purification fiber material is formed by introducing a halogen-containing compound as a linker into the styrene residues of the styrene-olefin copolymer constituting the aforementioned nonwoven fabric, thereby detaching the halogen from the linker and loading the ligand. That is, the liquid purification fiber material is formed by introducing a substituent containing a halogen group as a spacer group into the styrene-olefin copolymer, and replacing a portion of the halogen group with a ligand that interacts with substances harmful to living organisms.

[0059] The ligand is preferably greater than 0 relative to the dry mass of 1g of fiber material for liquid purification. m mol and 600 m Below mol, more preferably 0.02 mol. m mol or more and 290 m Below mol, more preferably 0.02 mol. m mol or more and 15 m Below mol, particularly preferably 0.04 mol. m mol or more and 12.5 m The content is below mol. This fibrous material for liquid purification sometimes contains halogens because a halogen-containing linking group is added to styrene during the manufacturing process. The halogen content in this fibrous material for liquid purification is preferably greater than 0.5% relative to the mass of the fibrous material. m mol / g and 900 m Below mol / g, more preferably greater than 0 m mol / g and 600 m Below mol / g, and more preferably greater than 0 mol / g m mol / g and 290 m Below mol / g, and more preferably greater than 0 mol / g mmol / g and 200 m Below mol / g, and more preferably greater than 0 mol / g m mol / g and 150 m Below mol / g, and more preferably greater than 0 mol / g m mol / g and 100 m Below mol / g, and more preferably greater than 0. m mol / g and 50 m Below mol / g. The term "halogen" here does not include halogens present in ligand-immobilized nonwoven fabrics (nonwoven fabrics for liquid purification) made by mixing polymers that originally contain halogens with a nonwoven fabric substrate. This lower halogen content reduces the frequency of cleaning by the user, resulting in greater ease of use.

[0060] Ligands that interact with harmful substances in organisms can be derived from amino acids, oligopeptides, peptides, sugars, oligosaccharides, polysaccharides, antibodies, lipopolysaccharides, lipids, proteoglycans, proteins, aptamers, and / or high molecular weight electrolytes, provided they have one or more nucleophilic substituents that react with the halogen of the aforementioned linking group. Examples of such nucleophilic substituents include amino, alkoxy, thiol, and ethynyl groups. Examples of ligands include tryptophan, L(... + Arginine, phenylalanine, monoethanolamine, ethylenediamine, heparin, azide, lactoferrin, gelatin. The ligand is preferably an amino group with adsorption capacity for endotoxins. Examples of ligands include antibiotics, polylysine, or polyethyleneimine, which are cationic polymers. As antibiotics, peptide compounds such as polymyxins and histrin 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 their sulfates and hydrochlorides, can also be used. One or more of the ligands described above can be used alone or in combination. The ligand is supported on the styrene-olefin copolymer through chemical bonding between the nucleophilic substituents and the spacer groups described above.

[0061] <Manufacturing Method of Fiber Materials for Liquid Purification> The liquid purification fiber material involved in this embodiment can be manufactured through the following halogenation process and ligand loading process.

[0062] The method for manufacturing the liquid purification fiber material according to this embodiment is a method for manufacturing any of the above-mentioned liquid purification fiber materials, including: a halogenation step, in which a halogen-containing compound is contacted with a nonwoven fabric substrate to obtain a halogenated nonwoven fabric; and a ligand loading step, in which the halogenated nonwoven fabric is dehalogenated to load ligands onto a styrene-olefin copolymer. The following describes each step in more detail.

[0063] (1) Halogenation process A nonwoven fabric substrate, 2-chloro-N-(hydroxymethyl)acetamide (an example of a halogen compound), paraformaldehyde, nitrobenzene, and concentrated sulfuric acid were added to a container and stirred to allow the halogen-containing compound to react with styrene residues in the styrene-olefin copolymer constituting the nonwoven fabric substrate. The nonwoven fabric was then removed from the container and washed with distilled water and methanol. The nonwoven fabric was then dried to obtain a chlorinated nonwoven fabric with the halogen-containing compound immobilized in styrene (an example of a halogenated nonwoven fabric; the same applies below).

[0064] (2) Ligand loading process In a container, a solution obtained by mixing the ligand or its salt with distilled water is added to the aforementioned chlorinated nonwoven fabric and a pH adjuster, and the mixture is stirred. The nonwoven fabric is then removed from the container and washed with distilled water to remove unreacted ligands and free hydrochloric acid. It is then dried to obtain a ligand-loaded nonwoven fabric. Through this process, the chlorine groups of the chlorinated nonwoven fabric are released to form hydrochloric acid, and the ligands are bonded to the chlorine group sites. Multiple ligands can also be bonded in this process. For example, to immobilize other ligands 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-immobilized nonwoven fabric is then added to this solution and stirred for a specified time. After rinsing repeatedly with distilled water and drying, a nonwoven fabric immobilized with ligands X and Y can be obtained. An example of ligand X is heparin. An example of ligand Y is lactoferrin.

[0065] <Washer> The cleaning device according to embodiments of the present invention is a device that internally contains the aforementioned liquid purification fiber material. The cleaning device is, for example, a blood purifier. The liquid purification fiber material is housed inside the blood purifier as a blood purification fiber material. Both the blood purification fiber material and the blood purifier are autoclave resistant. Another example of the cleaning device is a liquid cleaner for purifying liquid pharmaceuticals or liquid pharmaceutical raw materials. Both the liquid purification fiber material and the liquid cleaner are autoclave resistant. Another example of the cleaning device is a waste liquid cleaner for preventing the release of harmful substances from organisms into the environment. The liquid purification fiber material is housed inside the waste liquid cleaner as a waste liquid purification fiber material. Both the waste liquid purification fiber material and the waste liquid cleaner are autoclave resistant.

[0066] Figure 1A longitudinal cross-sectional view of the cleaner according to an embodiment of the present invention is shown.

[0067] The cleaner 100 has, for example, the structure described below. The container body 1 of the cleaner 100 has a tube 3 passing through its bottom 2 and is welded and fixed at the contact surface 4. An outlet 5 is provided at the upper part of the container body 1. Openings 6 and inlets 7 are provided at the upper and lower ends of the tube 3. The openings 6 are sealed by a stop 9 provided on the partition plate 8. A flow path for guiding liquid is formed on the inner side of the tube 3, and multiple through holes 10 are provided on the peripheral wall. Ligand-immobilized nonwoven fabric 12 is wound in multiple layers around the tube 3 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.

[0068] The cleaning device 100 is used as follows. A liquid containing substances harmful to living organisms flows into the flow path a1 from the opening 7, and is radially ejected from the through-hole 10 through the flow path a2 inside the tube. The liquid is purified by flowing radially a3 within a multi-layered ligand-immobilized nonwoven fabric (equivalent to a fibrous material for liquid purification) 12. Particulate matter is removed by the filter 13 through the gap a4 between the outermost layer of the nonwoven fabric 12 and the inner surface of the container body 1. The purified liquid is then recovered from the outlet hole 5 (a5).

[0069] According to the above embodiments, a liquid purification fiber material that reduces cleaning and suppresses particulate generation, and a cleaner equipped with the same, can be provided inexpensively. Furthermore, according to a part of the above embodiments, a liquid purification fiber material with excellent adsorption properties for harmful biological components, and a cleaner equipped with the same, can be provided.

[0070] Example Next, embodiments of the present invention will be described in detail using polymyxin immobilization as an example. It should be noted that the present invention is not limited to the following embodiments.

[0071] Experiment 1 (1) Manufacturing of nonwoven fabrics <Manufacturing Example 1> A 60-part (6 kg) mixture of a styrene-ethylene / butene-styrene polymer (SEBS, Kraton product number MD1648, manufactured by Kraton) containing 20% ​​by weight of styrene residues and 80% by weight of ethylene / butene residues, and a 40-part (4 kg) mixture of polypropylene (MOPLEN HP461X, LyondellBasell Industries) was melt-blown to produce a nonwoven fabric (3000 mm long × 250 mm wide × 0.3 mm thick). This nonwoven fabric was designated "Nonwoven Fabric A". The chlorine content in Nonwoven Fabric A was determined by combustion ion chromatography, and the result was less than 0.001 w / w% (0.2%). m mol / g).

[0072] (2) Chlorination of nonwoven fabrics <Manufacturing Example 2> In a 50 mL polypropylene container, 0.214 g of 2-chloro-N-(hydroxymethyl)acetamide (BLD Pharm, product number BLDP-05742), 0.011 g of paraformaldehyde (Fujifilm and Koichi Chemical, product number 168-20955), 20 mL of nitrobenzene (Fujifilm and Koichi Chemical, product number 143-01706), 1 mL of 95% concentrated sulfuric acid (Fujifilm and Koichi Chemical, product number 192-04696), and 1 g of nonwoven fabric A were added. The mixture was stirred inverted at 24°C for 3 hours. The nonwoven fabric was then removed from the container, washed with distilled water and methanol, and the residual washing solution was removed by drying in a vacuum dryer at 85°C to obtain chlorinated nonwoven fabric A. The chlorine content in the nonwoven fabric was determined by combustion ion chromatography, and the result was 0.151 w / w% (43). m mol / g).

[0073] <Manufacturing Example 3> The concentrated sulfuric acid was increased to 2 ml, and the conditions were otherwise identical to those in Manufacturing Example 2 above. The nonwoven fabric A was then chlorinated to obtain chlorinated nonwoven fabric B. The chlorine content in the nonwoven fabric was determined using combustion ion chromatography, and the result was 0.131 w / w% (37%). m mol / g).

[0074] <Manufacturing Example 4> The concentrated sulfuric acid was increased to 15 ml, and the conditions were otherwise identical to those in Manufacturing Example 3 above. The nonwoven fabric A was chlorinated to obtain chlorinated nonwoven fabric C. The chlorine content in the nonwoven fabric was determined using combustion ion chromatography, and the result was 0.096 w / w% (27). m mol / g).

[0075] <Manufacturing Example 5> In a 50 mL container made of PYREX (registered trademark), 0.214 g of 2-chloro-N-(hydroxymethyl)acetamide (same as in Manufacturing Example 2), 0.011 g of paraformaldehyde (same as in Manufacturing Example 2), 20 mL of nitrobenzene (same as in Manufacturing Example 2), 2 mL of 95% concentrated sulfuric acid (same as in Manufacturing Example 2), and 1 g of nonwoven fabric A were added. The mixture was stirred with a magnetic stirrer at room temperature (24°C) to allow the reaction to proceed. The nonwoven fabric was then removed, washed with distilled water and methanol, and the residual washing solution was dried using a vacuum dryer at 85°C to remove it, yielding chlorinated nonwoven fabric D. The chlorine content in the nonwoven fabric was determined using combustion ion chromatography, and the result was 0.095 w / w% (27). m mol / g).

[0076] <Manufacturing Example 6> In a 50 mL container made of PYREX (registered trademark), 0.214 g of 2-chloro-N-(hydroxymethyl)acetamide (same as in Manufacturing Example 2), 0.011 g of paraformaldehyde (same as in Manufacturing Example 2), 20 mL of nitrobenzene (same as in Manufacturing Example 2), 2 mL of 95% concentrated sulfuric acid (same as in Manufacturing Example 2), and 1 g of nonwoven fabric A were added. The mixture was stirred in a water bath at 24°C using a magnetic stirrer to allow the reaction to proceed. The nonwoven fabric was then removed, washed with distilled water and methanol, and the residual washing solution was dried using a vacuum dryer at 85°C to remove it, yielding chlorinated nonwoven fabric E. The chlorine content in the nonwoven fabric was determined using combustion ion chromatography, and the result was 0.073 w / w% (21). m mol / g).

[0077] <Manufacturing Example 7> The temperature in the water bath was set to 20°C, and all other conditions were the same as in Manufacturing Example 6, to obtain chlorinated nonwoven fabric F. The chlorine content in the nonwoven fabric was determined using combustion ion chromatography, and the result was 0.039 w / w% (11). m mol / g).

[0078] <Manufacturing Example 8> The temperature in the water bath was set to 14°C, and all other conditions were the same as in Manufacturing Example 6, to obtain chlorinated nonwoven fabric G. The chlorine content in the nonwoven fabric was determined using combustion ion chromatography, and the result was 0.019 w / w% (5). m mol / g).

[0079] <Manufacturing Example 9> The water bath temperature was set to 5°C, and all other conditions were the same as in Manufacturing Example 6, to obtain chlorinated nonwoven fabric H. The chlorine content in the nonwoven fabric was determined using combustion ion chromatography, and the result was 0.011 w / w% (3). mmol / g).

[0080] <Manufacturing Example 9A> The water bath temperature was set to 50°C, and all other conditions were the same as in Manufacturing Example 6, to obtain chlorinated nonwoven fabric H'. The chlorine content in the nonwoven fabric was determined using combustion ion chromatography, and the result was 0.52 w / w% (146). m mol / g).

[0081] (3) Polymyxinization of chlorinated nonwoven fabrics <Example 1> 15 mg of polymyxin B sulfate (product number 1-800-364-9897, manufactured by Cayman Chemical Company) was measured into a polypropylene container used in Manufacturing Example 2, and 15 ml of distilled water was added to dissolve it. 1 g of chlorinated nonwoven fabric B and 2 mg of magnesium oxide for pH adjustment (product number 131-00282, manufactured by Fujifilm and Koichi Chemical Co., Ltd.) were added to this reaction solution, and the mixture was stirred inverted for 2 hours at room temperature (25°C) to allow the reaction to proceed. Next, the nonwoven fabric was removed, washed with hydrochloric acid and distilled water, and then dried in a 40°C forced-air dryer for 3 hours to obtain polymyxin-loaded nonwoven fabric A.

[0082] <Example 2> The polymyxin B sulfate was set at 1 mg, and the other conditions were the same as in Example 1, to obtain a nonwoven fabric B loaded with polymyxin.

[0083] <Example 3> Using chlorinated nonwoven fabric G and polymyxin B sulfate at 1 mg, and otherwise under the same conditions as in Example 1, a nonwoven fabric C loaded with polymyxin was obtained.

[0084] <Example 4> Polymyxin B sulfate was set at 0.05 mg, and all other conditions were the same as in Example 1, to obtain a nonwoven fabric D loaded with polymyxin.

[0085] "Feature Evaluation 1" The properties of nonwoven fabrics A, B, C, and D loaded with polymyxin were evaluated. The control material used was Toray Industries, Inc.'s "TORAYMYXIN PMX-20R". Toray Industries, Inc.'s "TORAYMYXIN PMX-20R" does not have a nonwoven fabric structure; it is a woven fabric formed by coating polypropylene with styrene fibers. Therefore, it contains a large amount of chlorine.

[0086] (1) Amount of polymyxin added during the reaction Table 1 shows the amount of polymyxin added during the manufacturing of various polymyxin-loaded nonwoven fabric samples.

[0087] [Table 1] (2) Particle determination Table 2 compares and shows the particle counts generated when polymyxin-loaded nonwoven fabric B and the control material were subjected to two treatments. The test subjects were 0.17 g each of polymyxin-loaded nonwoven fabric B and the control material, cut into 2 cm square pieces. Each sample was placed in a 50 ml vial and rinsed 10 times with 10 ml of physiological saline. This removed the fibrils generated during cutting. Next, after drying, each sample was added to 10 ml of physiological saline and stirred inverted for 2 hours (10 rpm). Alternatively, after drying, each sample was added to 10 ml of physiological saline and ultrasonically cleaned for 20 minutes (40 kHz). The samples treated with both methods were then diluted and used in a particle counter (Beckman Coulter, model: HIAC 9703+. This was also used in subsequent particle determinations).

[0088] [Table 2] As shown in Table 2, under either treatment, sample B produced less particulate matter compared to the control material.

[0089] (3) Chlorine content Table 3 compares and shows the chlorine content of various samples A, B, C, D, and the control material. Chlorine content was determined by combustion ion chromatography. Specifically, the samples were combusted and attracted using a combustion-attraction system (model SQ-10) manufactured by Yanaco Machinery Development Institute, and separation and analysis were performed using an ion chromatography system (model ICA2000) and column (TSK-gel SuperIC-Anion HS) manufactured by Toa DKK Corporation. The same method was used in subsequent chlorine content determinations.

[0090] [Table 3] As shown in Table 3, samples A, B, C, and D all contain less chlorine than the comparative materials.

[0091] (4) pH changes after autoclaving 100 mg each of Sample B and the control material were washed with deionized water, dried, and then sterilized in 10 ml of physiological saline using an autoclave (Hiraya Seisakusho, model: HV-85IILV; the same applies to the following autoclaves). The pH change of the physiological saline before and after sterilization was investigated. The results showed that the pH of Sample B's physiological saline changed from 7.2 to 6.9, while the pH of the control material's physiological saline changed from 7.2 to 3.7. A HannaInstruments HI 2020-01 pH meter was used. This was also used in subsequent pH measurements. Based on these results, it is considered that, in the case of Sample B, compared to the control material, the physiological saline showed less pH change and less dechlorination. These results indicate that Sample B, compared to the control material, may significantly simplify the pre-use rinsing process.

[0092] (5) Adsorption capacity of endotoxins in water Table 4 shows the results of adsorption treatment of endotoxins (100 EU / ml × 20 ml) in water using 25 mg of various samples. The adsorption capacity of endotoxins was determined by turbidimetric time analysis. The reagents used in the analysis were the Limulus ES-2 Single Test Wako (manufactured by Fujifilm and Kochinosun Pharma Co., Ltd.), and the assay was performed using the Toxinometer ET-7000 (manufactured by Fujifilm and Kochinosun Pharma Co., Ltd.). The same method was used to investigate the adsorption capacity of endotoxins or other biologically harmful substances in subsequent studies. The removal rate (%) in the table is the value obtained by multiplying (blank concentration - measured concentration) / blank concentration by 100.

[0093] [Table 4] Through 2-hour and 4-hour adsorption tests, samples A, B, C, and D all showed higher removal rates than the control material.

[0094] (6) Adsorption capacity of endotoxins in human serum Table 5 shows the results of adsorption treatment of endotoxins (100 EU / ml × 3 ml) in human serum using 15 mg of various samples. The removal rate (%) in the table is the value obtained by multiplying (blank concentration - measured concentration) / blank concentration by 100.

[0095] [Table 5] Through 20-minute and 60-minute adsorption tests, samples A, B, C, and D all showed higher removal rates than the control material.

[0096] Experiment 2 (1) Manufacturing of nonwoven fabrics <Manufacturing Example 10> A 60-part (6 kg) mixture of a styrene-ethylene / butene-styrene polymer (SEBS, manufactured by Kraton, product number G1657) containing 10 wt% styrene residues and 90 wt% ethylene / butene residues, and a 40-part (4 kg) mixture of polypropylene (PWH02N, manufactured by Sun Allomer) was melt-blown to produce spun fibers and a nonwoven fabric (3000 mm long × 250 mm wide × 0.3 mm thick). This nonwoven fabric was designated "Nonwoven Fabric I". The chlorine content in Nonwoven Fabric I was determined using combustion ion chromatography, and the result was less than 0.2%. m mol / g.

[0097] (2) Chlorination of nonwoven fabrics <Manufacturing Example 11> In a 50 mL polypropylene container, add 0.214 g of 2-chloro-N-(hydroxymethyl)acetamide (BLD Pharm, product number BLDP-05742), 0.068 g of paraformaldehyde (Fujifilm and Koichi Pure Chemicals, product number 168-20955), 20 mL of nitrobenzene (Fujifilm and Koichi Pure Chemicals, product number 143-01706), 2 mL of 95% concentrated sulfuric acid (Fujifilm and Koichi Pure Chemicals, product number 192-04696), and 1 g of nonwoven fabric I. Stir the mixture inverted for 3 hours at 25°C. Then, remove the nonwoven fabric from the container, wash it with distilled water and methanol, and dry it in a 40°C forced-air dryer for 3 hours to obtain chlorinated nonwoven fabric I.

[0098] (3) Polymyxinization of chlorinated nonwoven fabrics <Example 5> 15 mg of polymyxin B sulfate (CAYMAN CHEMICAL COMPANY, product number 1-800-364-9897) was measured into a 50 mL polypropylene container and dissolved in 15 mL of distilled water. 1 g of chlorinated nonwoven fabric I and 2 mg of magnesium oxide for pH adjustment (Fujifilm and Koichi Chemical Co., Ltd., product number 131-00282) were added to this reaction solution, and the mixture was stirred inverted for 2 hours at 25°C to allow the reaction to proceed. The nonwoven fabric was then removed, washed with hydrochloric acid and distilled water, and dried in a 40°C forced-air dryer for 3 hours to obtain polymyxin-loaded nonwoven fabric I.

[0099] Experiment 3 (1) Manufacturing of nonwoven fabrics <Manufacturing Example 12> A 60-part (6 kg) mixture of a styrene-ethylene / butene-styrene polymer (SEBS, manufactured by Kraton, product number MD1648) containing 20 wt% styrene residues and 80 wt% ethylene / butene residues, and a 40-part (4 kg) mixture of polypropylene (PWH02N, manufactured by SunAllomer) was melt-blown to produce spun yarns and a nonwoven fabric (3000 mm long × 250 mm wide × 0.3 mm thick). This nonwoven fabric was designated "Nonwoven Fabric J". The chlorine content in Nonwoven Fabric J was determined using combustion ion chromatography, and the result was less than 0.2%. m mol / g.

[0100] (2) Chlorination of nonwoven fabrics <Manufacturing Example 13> 1g of nonwoven fabric J was added to replace 1g of nonwoven fabric I. Otherwise, chlorination was carried out under the same conditions as in manufacturing example 11 to obtain chlorinated nonwoven fabric J.

[0101] (3) Polymyxinization of chlorinated nonwoven fabrics <Example 6> 1g of chlorinated nonwoven fabric J was used instead of 1g of chlorinated nonwoven fabric I. Otherwise, polymyxinization was performed under the same conditions as in Example 5 to obtain nonwoven fabric J loaded with polymyxin.

[0102] Experiment 4 (1) Manufacturing of nonwoven fabrics <Manufacturing Example 14> A 60-part (6 kg) mixture of a styrene-ethylene / propylene-styrene polymer (SEPS, manufactured by Kuraray Co., Ltd., product number SEPTON 2002) containing 30 wt% styrene residues and 70 wt% ethylene / propylene residues, and a 40-part (4 kg) mixture of polypropylene (manufactured by Sun Allomer Co., Ltd., product number PWH02N), was melt-blown to produce spun yarns and a nonwoven fabric (3000 mm long × 250 mm wide × 0.3 mm thick) using the ALM-MB equipment manufactured by AIKI RIOTECH Co., Ltd. This nonwoven fabric was designated "Nonwoven Fabric K". The chlorine content in Nonwoven Fabric K was determined using combustion ion chromatography, and the result was less than 0.2%. m mol / g.

[0103] (2) Chlorination of nonwoven fabrics <Manufacturing Example 15> 1g of nonwoven fabric K was added to replace 1g of nonwoven fabric I. Otherwise, chlorination was carried out under the same conditions as in manufacturing example 11 to obtain chlorinated nonwoven fabric K.

[0104] (3) Polymyxinization of chlorinated nonwoven fabrics <Example 7> 1g of chlorinated nonwoven fabric K was used instead of 1g of chlorinated nonwoven fabric I. Otherwise, polymyxinization was performed under the same conditions as in Example 5 to obtain polymyxin-loaded nonwoven fabric K.

[0105] Experiment 5 (1) Manufacturing of nonwoven fabrics <Manufacturing Example 16> 60 parts by weight (6 kg) of a styrene-ethylene / butene-styrene polymer (referred to as SEBS, manufactured by Asahi Kasei Corporation, product number Tuftec H1517, 43 wt% styrene residues and 57 wt% ethylene / butene residues) and 40 parts by weight (4 kg) of polypropylene (manufactured by Sun Allomer Corporation, product number PWH02N) were mixed and spun into a nonwoven fabric (3000 mm long × 250 mm wide × 0.3 mm thick) using an ALM-MB equipment manufactured by AIKI RIOTECH via melt-blowing. This nonwoven fabric was designated "Nonwoven Fabric L". The chlorine content in Nonwoven Fabric L was determined using combustion ion chromatography, and the result was less than 0.2%. m mol / g.

[0106] (2) Chlorination of nonwoven fabrics <Manufacturing Example 17> 1g of nonwoven fabric L was added to replace 1g of nonwoven fabric I. Otherwise, chlorination was carried out under the same conditions as in manufacturing example 11 to obtain chlorinated nonwoven fabric L.

[0107] (3) Polymyxinization of chlorinated nonwoven fabrics <Example 8> 1g of chlorinated nonwoven fabric L was used instead of 1g of chlorinated nonwoven fabric I. Otherwise, polymyxinization was performed under the same conditions as in Example 5 to obtain polymyxin-loaded nonwoven fabric L.

[0108] "Characteristic Evaluation 2" Various properties of nonwoven fabrics I, J, K, and L loaded with polymyxin were evaluated. The control material used was Toray Industries, Inc.'s "TORAYMYXIN PMX-20R". In property evaluation 2, conditions not specifically mentioned were the same as those in property evaluation 1.

[0109] (1) Particle determination Tables 6 and 7 compare and show the particle counts generated when two treatments were applied to polymyxin-loaded nonwoven fabrics I, J, K, and L, and a control material. The subjects of the test were four types of polymyxin-loaded nonwoven fabrics cut into 2 cm squares and one comparative material. Each sample was placed in a 50 mL vial and rinsed 10 times with 10 mL of physiological saline. This removed the fibrils generated during cutting. Next, each sample was dried, and 10 mL of physiological saline was added, followed by inverted stirring with a vortex mixer for 2 hours (10 rpm). Alternatively, as another method, each sample was dried, and 10 mL of physiological saline was added, followed by ultrasonic cleaning for 20 minutes (40 kHz). The samples treated with both methods were then diluted and used in a particle counter. The results for the samples inverted with a vortex mixer are shown in Table 6, and the results for the ultrasonically cleaned samples are shown in Table 7. As shown in Tables 6 and 7, under either of the two treatments, the samples of Examples 5-8 produced less particulate matter compared to the comparative materials.

[0110] [Table 6] [Table 7] (2) Chlorine content Table 8 compares and shows the chlorine content of nonwoven fabrics I, J, K, L, and the control material after autoclaving and carrying polymyxin. The chlorine content was determined by combustion ion chromatography. As shown in Table 8, the samples in Examples 5–8 contained less chlorine than the control material.

[0111] [Table 8] (3) pH changes after autoclaving Table 9 shows the pH changes of the saline solution before and after autoclaving of polymyxin-loaded nonwoven fabrics I, J, L, and the control material in physiological saline. 100 mg each of the polymyxin-loaded nonwoven fabrics and the control material were washed with deionized water, dried, and then autoclaved in 10 mL of physiological saline (121°C, 20 min). The physiological saline solutions before and after sterilization were used to test a pH meter. Based on these results, the samples of each embodiment, compared to the control material, demonstrate the potential for significantly simplifying the pre-use rinsing process.

[0112] [Table 9] (4) Adsorption capacity of endotoxins in water Table 10 shows the adsorption results of endotoxin (100 EU / mL × 20 mL) in water by 25 mg each of nonwoven fabrics I, J, K, and the control material after autoclaving and loading polymyxin. The adsorption rate (%) in the table is obtained by multiplying (blank concentration - measured concentration) / blank concentration by 100. "Adsorption rate" can also be referred to as "removal rate". As can be seen from Table 10, the samples of each embodiment have a higher adsorption capacity than the control material.

[0113] [Table 10] (5) Adsorption capacity of endotoxins in human serum Table 11 shows the adsorption results of 15 mg each of autoclaved nonwoven fabric J loaded with polymyxin and control material on endotoxin (100 EU / mL × 3 mL) in serum. The adsorption rate (%) in the table is obtained by multiplying (blank concentration - measured concentration) / blank concentration by 100. "Adsorption rate" can also be referred to as "removal rate". As shown in Table 11, the samples of each embodiment have a higher adsorption capacity than the control material.

[0114] [Table 11] Experiment 6 (1) Manufacturing of nonwoven fabrics <Manufacturing Example 18> 20 parts by weight (2 kg) of a styrene-ethylene / butene-styrene polymer (SEBS, manufactured by Kraton, product number G1657) containing 10% by weight of styrene residues and 90% by weight of ethylene / butene residues, and 80 parts by weight (8 kg) of polypropylene (PWH02N, manufactured by Sun Allomer) were mixed and spun into a nonwoven fabric (3000 mm long × 250 mm wide × 0.3 mm thick) using the ALM-MB equipment manufactured by AIKI RIOTECH via melt-blowing. This nonwoven fabric was designated "Nonwoven Fabric M". The chlorine content in Nonwoven Fabric M was determined using combustion ion chromatography, and the result was less than 0.2%. m mol / g.

[0115] (2) Chlorination of nonwoven fabrics <Manufacturing Example 19> In a 50 mL polypropylene container, add 0.214 g of 2-chloro-N-(hydroxymethyl)acetamide (BLD Pharm, product number BLDP-05742), 0.068 g of paraformaldehyde (Fujifilm and Koichi Pure Chemicals, product number 168-20955), 20 mL of nitrobenzene (Fujifilm and Koichi Pure Chemicals, product number 143-01706), 2 mL of 95% concentrated sulfuric acid (Fujifilm and Koichi Pure Chemicals, product number 192-04696), and 1 g of nonwoven fabric M. Stir the mixture inverted for 3 hours at 25°C. Then, remove the nonwoven fabric from the container, wash it with distilled water and methanol, and dry it in a 40°C forced-air dryer for 3 hours to obtain chlorinated nonwoven fabric M.

[0116] (3) Polymyxinization of chlorinated nonwoven fabrics <Example 9> 15 mg of polymyxin B sulfate (CAYMAN CHEMICAL COMPANY, product number 1-800-364-9897) was measured into a 50 mL polypropylene container and dissolved in 15 mL of distilled water. 1 g of chlorinated nonwoven fabric M and 2 mg of magnesium oxide for pH adjustment (Fujifilm and Koichi Chemical Co., Ltd., product number 131-00282) were added to this reaction solution, and the mixture was stirred inverted for 2 hours at 25°C to allow the reaction to proceed. The nonwoven fabric was then removed, washed with hydrochloric acid and distilled water, and dried in a 40°C forced-air dryer for 3 hours to obtain polymyxin-loaded nonwoven fabric M.

[0117] Experiment 7 (1) Manufacturing of nonwoven fabrics <Manufacturing Example 20> 20 parts by weight (2 kg) of a styrene-ethylene / butene-styrene polymer (SEBS, manufactured by Kraton, product number MD1648, 20 wt% styrene residues and ethylene / butene residues) and 80 parts by weight (8 kg) of polypropylene (PWH02N, manufactured by SunAllomer) were mixed and spun into a nonwoven fabric (3000 mm long × 250 mm wide × 0.3 mm thick) using an ALM-MB apparatus manufactured by AIKI RIOTECH via meltblowing. This nonwoven fabric was designated "Nonwoven Fabric N". The chlorine content in Nonwoven Fabric N was determined using combustion ion chromatography, and the result was less than 0.2%. m mol / g.

[0118] (2) Chlorination of nonwoven fabrics <Manufacturing Example 21> 1g of nonwoven fabric N was added in place of 1g of nonwoven fabric M, and chlorination was carried out under the same conditions as in manufacturing example 19 to obtain chlorinated nonwoven fabric N.

[0119] (3) Polymyxinization of chlorinated nonwoven fabrics <Example 10> 1g of chlorinated nonwoven fabric N was used instead of 1g of chlorinated nonwoven fabric M. Otherwise, polymyxinization was performed under the same conditions as in Example 9 to obtain nonwoven fabric N loaded with polymyxin.

[0120] Experiment 8 (1) Manufacturing of nonwoven fabrics <Manufacturing Example 22> 90 parts by weight (9 kg) of a styrene-ethylene / butene-styrene polymer (designated SEBS, product number MD1648, manufactured by Kraton, with 20% by weight of styrene residues and 80% by weight of ethylene / butene residues) and 10 parts by weight (1 kg) of polypropylene (product number PWH02N, manufactured by SunAllomer) were mixed and spun into a nonwoven fabric (3000 mm in length × 250 mm in width × 0.3 mm in thickness) using an ALM-MB apparatus manufactured by AIKI RIOTECH via melt-blowing. This nonwoven fabric was designated "Nonwoven Fabric O". The chlorine content in Nonwoven Fabric O was determined using combustion ion chromatography, and the result was less than 0.2%. m mol / g.

[0121] (2) Chlorination of nonwoven fabrics <Manufacturing Example 23> 1g of nonwoven fabric O was added to replace 1g of nonwoven fabric M, and chlorination was carried out under the same conditions as in manufacturing example 19 to obtain chlorinated nonwoven fabric O.

[0122] (3) Polymyxinization of chlorinated nonwoven fabrics <Example 11> 1g of chlorinated nonwoven fabric O was used instead of 1g of chlorinated nonwoven fabric M. Otherwise, polymyxinization was performed under the same conditions as in Example 9 to obtain nonwoven fabric O loaded with polymyxin.

[0123] Experiment 9 (1) Manufacturing of nonwoven fabrics <Manufacturing Example 24> 95 parts by weight (9.5 kg) of a styrene-ethylene / butene-styrene polymer (SEBS, Kraton product number MD1648, manufactured by Kraton) containing 20% ​​by weight of styrene residues and 80% by weight of ethylene / butene residues, and 5 parts by weight (0.5 kg) of polypropylene (SunAllomer product number PWH02N), were mixed and spun into a nonwoven fabric (3000 mm long × 250 mm wide × 0.3 mm thick) using an ALM-MB equipment manufactured by AIKI RIOTECH via meltblowing. This nonwoven fabric was designated "Nonwoven Fabric P". The chlorine content in Nonwoven Fabric P was determined using combustion ion chromatography, and the result was less than 0.2%. m mol / g.

[0124] (2) Chlorination of nonwoven fabrics <Manufacturing Example 25> 1g of nonwoven fabric P was added in place of 1g of nonwoven fabric M, and chlorination was carried out under the same conditions as in manufacturing example 19 to obtain chlorinated nonwoven fabric P.

[0125] (3) Polymyxinization of chlorinated nonwoven fabrics <Comparative Example 1> 1g of chlorinated nonwoven fabric P was used instead of 1g of chlorinated nonwoven fabric M. Otherwise, polymyxinization was performed under the same conditions as in Example 9 to obtain polymyxin-loaded nonwoven fabric P. The nonwoven fabrics loaded with polymyxin P have strong adhesion to each other and cannot be rolled into a blood purification column, thus they cannot be used for property evaluation.

[0126] Experiment 10 (1) Chlorination of nonwoven fabrics 4.84 g of 2-chloro-N-(hydroxymethyl)acetamide (a halogen compound), 1.54 g of paraformaldehyde, 339 ml of nitrobenzene, and 45.2 ml of sulfuric acid were added to a polypropylene container. 22.6 g of a nonwoven fabric containing a styrene-olefin copolymer (Kraton product number MD1648:PP = 9:1) was then added. The mixture was stirred at 160 rpm for 3 hours at 25°C in a shaking incubator to allow the reaction to proceed. The fabric was then washed three times with 200 ml of distilled water and six times with 600 ml of methanol to remove residual nitrobenzene. Finally, it was washed three more times with 500 ml of distilled water. The final product was dried at 40°C for 2 hours using a constant-temperature forced-air dryer to obtain the chlorinated nonwoven fabric Q, which incorporates chlorine groups.

[0127] <Example 12> (2) Tryptophanization of chlorinated nonwoven fabrics For chlorinated nonwoven fabric Q, the immobilization of L-tryptophan (manufactured by Fujifilm and Kojun Pharmaceutical Co., Ltd.) was attempted according to the following procedure. 45 ml of a 1 wt% aqueous solution of tryptophan was added to a polypropylene container, along with 300 mg of chlorinated nonwoven fabric Q and 6 mg of magnesium oxide for pH adjustment. The mixture was stirred inverted 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 40°C forced-air dryer for 3 hours to obtain the nonwoven fabric infused with tryptophan. Figure 2 As shown, the introduction of tryptophan was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the fiber with introduced tryptophan using an ATR-FT-IR (manufactured by Nicolet FT-IR Thermofisher Scientific) with the tryptophan spectrum in the database.

[0128] Experiment 11 <Example 13> L-arginination of chlorinated nonwoven fabrics For chlorinated nonwoven fabric Q, try L( ) according to the following guidelines. + Immobilization of arginine (manufactured by Fujifilm and Koichi Chemical Co., Ltd.). 45 ml of a 1 wt% aqueous solution of arginine was added to a polypropylene container, along with 300 mg of chlorinated nonwoven fabric Q and 6 mg of magnesium oxide for pH adjustment. The mixture was stirred inverted for 2 hours at room temperature (25°C) with the pH around 9.4. The nonwoven fabric was then removed, washed with hydrochloric acid and distilled water, and dried in a 40°C forced-air dryer for 3 hours to obtain the arginine-infused nonwoven fabric. The nonwoven fabric was analyzed using SEM-EDS (manufactured by Hitachi High-Technologies, model: Miniscope TM3000), and the results are shown in Table 12, confirming the introduction of nitrogen from arginine. Furthermore, as... Figure 3 As shown, the introduction of arginine was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the fiber with introduced arginine using an ATR-FT-IR (manufactured by Nicolet FT-IR Thermofisher Scientific) with the arginine spectrum in the database.

[0129] [Table 12] Experiment 12 <Example 14> Phenylalanineation of chlorinated nonwoven fabrics For chlorinated nonwoven fabric Q, the immobilization of phenylalanine (manufactured by Fujifilm and Koichi Chemical Co., Ltd.) was attempted according to the following procedure. 25 ml of a 1 wt% aqueous solution of phenylalanine was added to a polypropylene container, along with 1 g of chlorinated nonwoven fabric Q and 4 mg of magnesium oxide for pH adjustment. The mixture was stirred inverted 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 0.1N hydrochloric acid and three times with 50 ml of distilled water. It was then further washed three times with 30 ml of 0.018% Triton solution. Additionally, it underwent filtration washing with 200 ml of 0.018% Triton solution and filtration washing with 200 ml of distilled water. Finally, it was dried in a 40°C forced-air dryer for 2 hours to obtain the nonwoven fabric infused with phenylalanine. Figure 4 As shown, the introduction of phenylalanine was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the fiber infused with phenylalanine with the phenylalanine difference spectrum using an ATR-FT-IR (manufactured by Nicolet FT-IR Thermofisher Scientific) with the phenylalanine spectrum in the database.

[0130] Experiment 13 <Example 15> Monoethanolamine of chlorinated nonwoven fabrics For chlorinated nonwoven fabric Q, immobilization with monoethanolamine (manufactured by Fujifilm and Koichi Chemical Co., Ltd.) was attempted according to the following procedure. This is equivalent to introducing OH groups into the chlorinated nonwoven fabric. 25 ml of a 1 wt% aqueous solution of monoethanolamine was added to a polypropylene container, along with 1 g of chlorinated nonwoven fabric Q and 4 mg of magnesium oxide for pH adjustment. The mixture was stirred inverted 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 0.1N hydrochloric acid, three times with 50 ml of distilled water, and then further washed three times with 30 ml of 0.018% Triton solution. Additionally, a filtration wash was performed using 200 ml of 0.018% Triton solution and then a filtration wash using 200 ml of distilled water. Finally, the fabric was dried in a 40°C forced-air dryer for 2 hours to obtain the nonwoven fabric with introduced OH groups. Figure 5 As shown, the introduction of OH groups was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the fiber with introduced monoethanolamine using an ATR-FT-IR (manufactured by Nicolet FT-IR Thermofisher Scientific) with the monoethanolamine spectrum in the database.

[0131] Experiment 14 <Example 16> Ethylening of chlorinated nonwoven fabrics For chlorinated nonwoven fabric Q, immobilization with ethylenediamine (manufactured by Fujifilm and Koichi Chemical Co., Ltd.) was attempted according to the following procedure. This is equivalent to introducing an amino group into the chlorinated nonwoven fabric. 25 ml of a 1 wt% ethylenediamine aqueous solution was added to a polypropylene container, along with 1 g of chlorinated nonwoven fabric Q and 4 mg of magnesium oxide for pH adjustment. The mixture was stirred inverted 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 0.1N hydrochloric acid, three times with 50 ml of distilled water, and then further washed three times with 30 ml of 0.018% Triton solution. Additionally, it underwent filtration washing with 200 ml of 0.018% Triton solution and filtration washing with 200 ml of distilled water, followed by drying in a 40°C forced-air dryer for 2 hours to obtain the amino-introduced nonwoven fabric. Figure 6 As shown, the introduction of amino groups was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the fiber with introduced ethylenediamine using an ATR-FT-IR (manufactured by Nicolet FT-IR Thermofisher Scientific) with ethylenediamine in a database.

[0132] Experiment 15 <Example 17> Heparinization of ethylenediamined fibers using chlorinated nonwoven fabric For the amino-introduced nonwoven fabric obtained in Example 16 of Experiment 14, heparin immobilization was attempted according to the following procedure. 10 mg of heparin treated with sodium periodate (heparin dialdehyde) was added to a 15 ml polypropylene container, followed by 10 ml of hydrochloric acid aqueous solution at pH 4, to prepare a 0.1 wt% solution (approximately 200 units / ml). 100 mg of the amino-introduced nonwoven fabric obtained in Example 16 was added to this solution. After reacting at approximately pH 4 at 25°C for 24 hours (vortexed at 100 rpm), the fabric was thoroughly washed with distilled water and dried in a 40°C forced-air dryer for 3 hours to obtain the heparin-immobilized nonwoven fabric. Figure 7 As shown, the introduction of heparin was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum of untreated fiber from the IR spectrum of fiber with that of heparin-introduced fiber using an ATR-FT-IR (manufactured by Nicolet FT-IR Thermofisher Scientific) with the FT-IR spectrum of heparin-aldinated fiber.

[0133] Experiment 16 <Example 18> Azide treatment of chlorinated nonwoven fabrics For chlorinated nonwoven fabric Q, attempt to immobilize the azide groups using the following method: Add 100 mg of sodium azide to a 15 ml polypropylene container, then add 10 ml of distilled water to prepare a 1 wt% aqueous solution. Add the chlorinated nonwoven fabric Q to this solution. After reacting at approximately pH 8 at 25°C for 24 hours (vortexing at 100 rpm), thoroughly wash with distilled water, and dry in a 40°C forced-air dryer for 3 hours to obtain the azide-treated nonwoven fabric. Figure 8 As shown, regarding the introduction of azide groups, the obtained nonwoven fabric was subjected to ATR-FT-IR measurements in the same manner as in Experiment 14, and the introduction of azide groups was confirmed by comparing the spectra of sodium azide in the database.

[0134] Experiment 17 <Example 19> Lactoferrinization of heparinized fibers using chlorinated nonwoven fabric Functional adsorbents were developed by immobilizing heparin-interacting functional proteins onto nonwoven fabrics. The heparin-immobilized nonwoven fabric synthesized in Example 17 of Experiment 15 not only improved blood compatibility but also interacted with many functional molecules, making it a viable basis for highly functionalized fibers. Heparin is known to have a strong interaction with lactoferrin. Therefore, by immobilizing lactoferrin, interactions with LPS traps, viral traps, electrostatic interactions with LDL, etc., can be expected.

[0135] First, 100 mg of lactoferrin (derived from milk, manufactured by Fujifilm, Biochemical Use 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. After soaking at room temperature for 4 hours while stirring at 40 rpm, the mixture was vigorously rinsed 5 times with 20 ml of distilled water at approximately 300 rpm, and then dried at room temperature to obtain the lactoferrin-heparin-immobilized nonwoven fabric. Figure 9 As shown, the introduction of lactoferrin was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum of the fiber containing heparin from the IR spectrum of the fiber containing lactoferrin using an ATR-FT-IR (manufactured by NicoletFT-IR Thermofisher Scientific) with the FT-IR spectrum of lactoferrin.

[0136] Experiment 18 <Example 20> Alkali-treated gelatinization of chlorinated nonwoven fabric For the chlorinated nonwoven fabric Q, alkali-treated gelatin was immobilized according to the following procedure. Alkali-treated bovine bone gelatin (LET-N230) manufactured by Nitta Gelatin Co., Ltd. was used. 15 ml of a 1.6 wt% aqueous solution of alkali-treated gelatin was added to a polypropylene container, along with 100 mg of chlorinated nonwoven fabric Q and 2 mg of magnesium oxide for pH adjustment. The mixture was stirred inverted for 2 hours at room temperature (25°C) with the pH around 9.4 to allow the reaction to proceed. The nonwoven fabric was then removed, washed with hydrochloric acid and distilled water, and dried in a 40°C forced-air dryer for 3 hours to obtain the nonwoven fabric infused with alkali-treated gelatin. SEM-EDS analysis (Made by Hitachi High-Technologies, model: Miniscope TM3000) was performed on this nonwoven fabric, and the results are shown in Table 13, confirming the introduction of nitrogen from the gelatin. Additionally, as... Figure 10 As shown, the change in nitrogen concentration from gelatin on the outermost surface was measured using XPS (manufactured by Nippon Electron Ltd., model: JPS-9010MC), thus confirming the introduction of nitrogen on the outermost surface.

[0137] [Table 13] Experiment 19 <Example 21> Acid-processed gelatinization of chlorinated nonwoven fabrics For the chlorinated nonwoven fabric Q, acid-treated gelatin immobilization was performed according to the following procedure. The gelatin used was acid-treated pigskin gelatin (LET-NP250) manufactured by Nitta Gelatin Co., Ltd. 15 ml of a 1.6 wt% aqueous solution of the acid-treated gelatin was added to a polypropylene container, along with 100 mg of chlorinated nonwoven fabric Q and 2 mg of magnesium oxide for pH adjustment. The mixture was stirred inverted for 2 hours at room temperature (25°C) with the pH around 9.4 to allow the reaction to proceed. The nonwoven fabric was then removed, washed with hydrochloric acid and distilled water, and dried in a 40°C forced-air dryer for 3 hours to obtain the nonwoven fabric infused with the acid-treated gelatin. SEM-EDS (Made by Hitachi High-Technologies, model: Miniscope TM3000) analysis of the nonwoven fabric was performed, and the results are shown in Table 14, confirming the introduction of nitrogen from the gelatin. Additionally, as... Figure 11 As shown, the change in nitrogen concentration from gelatin on the outermost surface was measured using XPS (manufactured by Nippon Electron Ltd., model: JPS-9010MC), thereby confirming the introduction of nitrogen on the outermost surface.

[0138] [Table 14] "Feature Evaluation 3" The properties of the various ligand-loaded nonwoven fabrics in Examples 9-21 were evaluated. The control material used was Toray Industries, Inc.'s "TORAYMYXIN PMX-20R". In property evaluation 3, the conditions not specifically mentioned were the same as those in property evaluation 1.

[0139] (1) Particle determination Tables 15 and 16 compare and show the number of particles generated when two treatments were applied to various ligand-loaded nonwoven fabrics and comparative materials. The treatment and measurement methods for the test objects were the same as in Characteristic Evaluation 2. The results for samples stirred by inverting with a vortex mixer are shown in Table 15, and the results for samples ultrasonically cleaned are shown in Table 16. As can be seen from Tables 15 and 16, in either treatment case, the samples of each embodiment generated fewer particles compared to the control material.

[0140] [Table 15] [Table 16] (2) Chlorine content Table 17 compares and shows the chlorine content (M, N, O) of the polymyxin-loaded nonwoven fabric after autoclaving and that of the comparative material. The chlorine content was determined by combustion ion chromatography. As shown in Table 17, the samples of Examples 9–11 contained less chlorine than the comparative material.

[0141] [Table 17] (3) pH changes after autoclaving Table 18 shows the pH changes of physiological saline before and after autoclaving various ligand-loaded nonwoven fabrics and control materials in physiological saline. The treatment and measurement conditions for the test objects were the same as those in Characteristic Evaluation 2. According to the results, the pH changes of the samples in each embodiment were small compared to the control materials. Therefore, the samples in each embodiment show the potential to significantly simplify the rinsing process before use.

[0142] [Table 18] (4) Adsorption capacity of endotoxins in water Table 19 shows the adsorption results after 2 hours of adsorption treatment, in which 5 mg of various ligand-loaded nonwoven fabrics and control materials, after autoclaving, were immersed in 4 ml of ion-exchanged water with an endotoxin concentration of 100 EU / mL, and stirred at 37°C and 10 rpm. The adsorption rate (%) in the table is obtained by multiplying (blank concentration - measured concentration) / blank concentration by 100.

[0143] [Table 19] In nonwoven fabrics incorporating amino acids as ligands, the adsorption mechanism of endotoxins was well observed. In nonwoven fabrics immobilized with tryptophan, which became hydrophobic and amino groups, a high endotoxin adsorption rate of approximately 60% was observed. This result is presumably because endotoxin adsorption is not solely caused by charge, but is related to multiple factors from the structure and chemical composition of the ligands, particularly the distance between the charged and hydrophobic regions, which significantly influences the strength of the interaction. It is known that nonwoven fabrics using low-molecular-weight compounds such as ethylenediamine and monoethanolamine as raw materials, converted into amino and OH groups, can also adsorb endotoxins with high efficiencies of 97% and 98%, respectively. This is believed to be because the introduced ligands are extremely small molecules; therefore, the hydrophobicity of the substrate fiber developed in this invention is close to the charge generated by the introduced ligands, thus enabling more efficient removal. It can be inexpensively applied to filters for removing harmful substances from water.

[0144] It is also possible to introduce ligands for polysaccharides and glycoproteins. An example was comparing the endotoxin removal capabilities of heparin-immobilized nonwoven fabric and nonwoven fabric infused with lactoferrin, which is known to have a strong interaction with heparin. Heparin has strong anticoagulant activity and offers significant advantages in removing harmful substances from the blood by improving blood compatibility. However, due to its negative charge, it electrostatically repels the negative charge of endotoxin, resulting in a removal rate of only 18%. On the other hand, lactoferrin is known to have a strong interaction with LPS. It is immobilized through this strong interaction with heparin and carries a positive charge under physiological conditions. In nonwoven fabrics immobilized with lactoferrin, a high efficiency of 91% endotoxin removal was confirmed. Therefore, a nonwoven fabric can be obtained that, while maintaining heparin-based blood compatibility, can remove endotoxins and lipids from the blood through a strong interaction with lactoferrin bound to free iron in the blood.

[0145] Regarding gelatin, known as a protein and exhibiting interactions with cell adhesion scaffolds, MMPs, etc., endotoxin adsorption experiments were conducted on nonwoven fabrics using gelatin manufactured through two different treatments as immobilized ligands. In the alkali-treated gelatin-immobilized nonwoven fabric, the isoelectric point of the immobilized alkali-treated bovine bone gelatin was approximately around pH 5, carrying a negative charge in the neutral region of pH 7.4. Therefore, in the adsorption experiment in negatively charged LPS water, a removal rate of approximately 38.5% was observed after 2 hours, which is the result of removing a certain amount of LPS due to the influence of hydrophobic interactions, etc. It is believed that effective adsorption of positively charged LDL, etc., is observed around pH 7.4. On the other hand, in the nonwoven fabric immobilized with acid-treated gelatin, the isoelectric point of the immobilized porcine skin acid-treated gelatin was close to that of the raw collagen, approximately around pH 8-9, carrying a positive charge in the neutral region of pH 7.4. Therefore, in the adsorption experiment of negatively charged LPS in water, a removal rate of approximately 98% was observed after 2 hours, confirming its effectiveness. Overall, the ligands with both positive charge and hydrophobic moieties, used for LPS adsorption, exhibited high removal efficiency.

[0146] (5) Adsorption capacity of proteins, lipids and iron in normal serum The following eight types of nonwoven fabrics were used to provide ligand-loaded nonwoven fabrics for testing.

[0147] Polymyxin-immobilized nonwoven fabric (Example 2) PMx 10.4mg Tryptophan-immobilized nonwoven fabric (Example 12) TPF 10.3mg Arginine-immobilized nonwoven fabric (Example 13) ALG 10.6mg Phenylalanine immobilized nonwoven fabric (Example 14) PHA 10.1mg Ethylenediamine immobilized nonwoven fabric (Example 16) EDA 9.8mg Heparin-immobilized nonwoven fabric (Example 17) HEP 9.9mg Heparin-lactoferrin immobilized nonwoven fabric (Example 19) HEP-LF 10.2mg Acid-treated gelatin-immobilized nonwoven fabric (Example 21) ATG 10.7mg Beforehand, approximately 10 mg of finely chopped sample was added to each 5 ml glass tube, and primed thoroughly with heparinized saline. Just before the experiment, the priming solution was removed using a pipette, and 2 ml of porcine serum was added at 37°C. Specifically, calcium chloride was added to the blood to activate the coagulation system, and after 30 minutes, the blood was centrifuged at 1200G to collect the serum. At this time, 0.5 ml of untreated serum was collected in a control tube as the control serum for the test. Then, 2 ml of serum was allocated to each of the eight sample tubes, and the adsorption experiment was performed using a 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 as the serum test sample. The test items were total protein, albumin, iron, total cholesterol, free cholesterol, ester cholesterol, triglycerides, LDL, and HDL. The test results are shown in Table 20. Adsorption experiments confirmed the adsorption of lipids such as total cholesterol, free cholesterol, ester cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in nonwoven fabrics using heparin-lactoferrin, tryptophan, and acid-treated gelatin as ligands.

[0148] [Table 20] (6) Adsorption capacity of bilirubin and bile acids in normal serum In the experiment, eight types of nonwoven fabrics were used to investigate the adsorption capacity of proteins, lipids, and iron in the normal serum described in (5). Additionally, the control serum and serum test samples were prepared under the same conditions as those used for the adsorption capacity of proteins, lipids, and iron in the normal serum described in (5). The tests included total bilirubin, direct bilirubin, indirect bilirubin, and total bile acids. The results are shown in Table 21.

[0149] As shown in Table 21, approximately 8% removal capacity was confirmed in positively charged and hydrophobic tryptophan, lactoferrin, and acid-treated gelatin. Bilirubin, a negatively charged molecule, was used in nonwoven fabrics with arginine, the most basic amino acid ligand, as an adsorbent. It was confirmed that this fabric could adsorb 33% of total bilirubin and approximately 100% of indirect bilirubin, demonstrating its potential as a useful adsorbent.

[0150] [Table 21] Industrial availability This invention can be applied to blood purification, purification of pharmaceuticals and their raw material liquids, waste liquid treatment, etc.

Claims

1. A fiber material for liquid purification, wherein, The fiber material used for liquid purification uses a non-woven fabric substrate. The fiber material used for liquid purification is used to remove harmful substances from liquids. The nonwoven fabric substrate contains a mixture of polyolefin and styrene-olefin copolymer resins within a single fiber. The mass ratio of the polyolefin to the mixed resin is 10% by mass or more and 80% by mass or less. The total mass ratio of styrene residues to the styrene-olefin copolymer is more than 5% by mass and less than 50% by mass. The styrene-olefin copolymer contains substituents comprising halogen groups as spacer groups. A portion of the halogen groups of the spacer group are replaced by ligands that interact with substances harmful to organisms. The halogen content in the fiber material for liquid purification is greater than 0% relative to the mass of the fiber material. μ mol / g and 900 μ Below mol / g, The ligands are tryptophan and L-aminobutyric acid, which interact with harmful substances in organisms. + Arginine, phenylalanine, monoethanolamine, ethylenediamine, heparin, azide, lactoferrin, gelatin, or polymyxins. The ligand has one or more nucleophilic substituents. The ligand is supported on the styrene-olefin copolymer through chemical bonding of the nucleophilic substituent to the spacer group.

2. The fiber material for liquid purification according to claim 1, wherein, The mass ratio of the polyolefin to the mass of the mixed resin is 20% by mass or more and 50% by mass or less.

3. The fiber material for liquid purification according to claim 1, wherein, The polyolefin is present in a mass ratio of 80% to the mass of the mixed resin, and the ligand is a polymyxin.

4. The fiber material for liquid purification according to any one of claims 1 to 3, wherein, The styrene-olefin copolymer is at least one copolymer selected from the group consisting of a saturated copolymer formed by polymerizing an aromatic vinyl compound with an olefin having one double bond, an unsaturated copolymer formed by polymerizing an aromatic vinyl compound with a diene having two conjugated double bonds, and a hydrogenated saturated copolymer obtained by hydrogenating the unsaturated copolymer.

5. The fiber material for liquid purification according to any one of claims 1 to 3, wherein, The halogen content in the fiber material for liquid purification is greater than 0% relative to the mass of the fiber material. μ mol / g and 290 μ Below mol / g.

6. The fiber material for liquid purification according to any one of claims 1 to 3, wherein, The fiber material for liquid purification incorporates at least two of the aforementioned ligands.

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