NONWOVEN SUBSTRATE, FIBROUS MATERIAL FOR LIQUID CLARIFICTION, PRODUCTION METHOD FOR SAID MATERIAL, AND CLEANER EQUIPPED WITH SAID MATERIAL

Abstract

Provided are a fiber material for liquid purification, being inexpensive, capable of reducing cleaning, and suppressing the generation of fine particles, and a cleaning device including the same. The present invention relates to a nonwoven fabric base material containing a mixed resin of polyolefin and a styrene-olefin copolymer in a single fiber, which is used as a fiber material for liquid purification for removing a biotoxic substance from liquid, wherein the mass ratio of the polyolefin to the mass of 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 mass of the styrene-olefin copolymer is 5% by mass or more and 50% by mass or less, a fiber material for liquid purification including the nonwoven fabric base material, a method for producing the material, and a cleaning device including the material.

Claims

1. A nonwoven fabric base material comprising a mixed resin of polyolefin and a styrene-olefin copolymer in a single fiber, which is used as a fiber material for liquid purification for removing a biotoxic substance from liquid, wherein a mass ratio of the polyolefin to a mass of the mixed resin is 10% by mass or more and 80% by mass or less, and a mass ratio of all styrene residues to a mass of the styrene-olefin copolymer is 5% by mass or more and 50% by mass or less.

2. The nonwoven fabric base material according to claim 1, 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 nonwoven fabric base material according to claim 1, wherein the styrene-olefin copolymer is at least one copolymer selected from the group consisting of a saturated copolymer obtained by polymerization 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 the unsaturated copolymer.

4. A fiber material for liquid purification, comprising the nonwoven fabric base material according to claim 1, wherein a substituent containing a halogen group is introduced into the styrene-olefin copolymer as a spacer, some of the halogen groups of the spacer is replaced by a ligand that interacts with a biotoxic substance, and a halogen content in the fiber material for liquid purification is more than 0 mol/g and 900 mol/g or less relative to a mass of the fiber material for liquid purification.

5. The fiber material for liquid purification according to claim 4, wherein the halogen content in the fiber material for liquid purification is more than 0 mol/g and 290 mol/g or less relative to the mass of the fiber material for liquid purification.

6. The fiber material for liquid purification according to claim 4, wherein the ligand is derived from an amino acid, oligopeptide, peptide, saccharide, oligopolysaccharide, antibody, lipopolysaccharide, lipid, proteoglycan, protein, aptamer and/or polyelectrolyte that interact with a biotoxic substance, the ligand has one or more nucleophilic substituents, and the ligand is supported on the styrene-olefin copolymer by chemical bonding between the nucleophilic substituent and the spacer.

7. A method for producing the fiber material for liquid purification according to claim 4, the method comprising: a halogenation step of contacting a halogen compound with the nonwoven fabric base material to provide a halogenated nonwoven fabric; and a ligand supporting step of dehalogenating the halogenated nonwoven fabric to allow the ligand to be supported on the styrene-olefin copolymer.

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

9. A cleaning device comprising the fiber material for liquid purification according to claim 4 therein.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0060] FIG. 1 shows a longitudinal sectional view of a cleaning device according to an embodiment of the present invention.

[0061] FIG. 2 shows a difference spectrum of a tryptophan-immobilized fiber.

[0062] FIG. 3 shows a difference spectrum of an arginine-immobilized fiber.

[0063] FIG. 4 shows a difference spectrum of a phenylalanine-immobilized fiber.

[0064] FIG. 5 shows a difference spectrum of a monoethanolamine-immobilized fiber.

[0065] FIG. 6 shows a difference spectrum of an ethylenediamine-immobilized fiber.

[0066] FIG. 7 shows a difference spectrum of a heparin-immobilized fiber.

[0067] FIG. 8 shows a difference spectrum of an azide group-immobilized fiber.

[0068] FIG. 9 shows a difference spectrum of a lactoferrin-heparin-immobilized fiber.

[0069] FIG. 10 shows a XPS measurement result in Experiment 19.

[0070] FIG. 11 shows a XPS measurement result in Experiment 20.

REFERENCE SIGNS LIST

[0071] 1: Container body [0072] 2: Bottom [0073] 3: Pipe [0074] 4: Contact surface [0075] 5: Outlet [0076] 6: Opening [0077] 7: Inlet [0078] 8: Partition plate [0079] 9: Stopper [0080] 10: Through hole [0081] 11: Internal bottom surface [0082] 12: Ligand-immobilized nonwoven fabric [0083] 13: Filter [0084] 100: Cleaning device

DESCRIPTION OF EMBODIMENTS

[0085] Embodiments of the present invention will be described. The embodiments described below do not limit the claimed invention, and not all elements and combinations thereof described in the embodiments are not necessarily essential to the solution of the present invention.

<Nonwoven Fabric Base Material>

[0086] The nonwoven fabric base material according to the embodiment of the present invention is used as a fiber material for liquid purification for adsorbing and recovering biotoxic substances from solutions such as blood, plasma, serum, drugs, cell culture fluid, and water. This nonwoven fabric base material consists of a melt-mixed resin of a polyolefin and a styrene-olefin copolymer, and is in the form of a nonwoven fabric of a blend fiber containing the polyolefin and the styrene-olefin copolymer in a single fiber. The nonwoven fabric base material has, for example, the form of a sheet. There are no particular limitations on the planar area of the nonwoven fabric base material. The thickness of the nonwoven fabric base material is, for example, 20 m or more and 3000 m or less.

[0087] The blend fiber of the polyolefin and styrene-olefin copolymer preferably has an average diameter of 50 nm or more and 500 m or less, more preferably an average diameter of 80 nm or more and 40 m or less, and still more preferably an average diameter of 100 nm or more and 30 m or less. In addition, the blend fiber preferably has an average length of 5 mm or more, more preferably an average length of 10 mm or more, and still more preferably an average length of 20 mm or more. In the present application, the average diameter refers to a value obtained by randomly observing a cross section of the fiber observed in 100 fields of view using a scanning electron microscope, a transmission electron microscope, or a digital microscope, determining the diameter when each cross section is converted into a circle, and averaging the obtained diameters for the 100 fields of view. The average length refers to a value obtained by randomly observing 100 fields of view of the side surface of the fiber using an optical microscope, determining the length of each fiber when each fiber is made into a straight line, and averaging the obtained lengths for the 100 fields of view. The same applies to the average diameter and average length that appear below.

[0088] The styrene-olefin copolymer is a polymer of two or more styrene monomers and two or more olefin monomers, may be any of copolymers such as a block copolymer, a random copolymer, an alternating copolymer, or a graft copolymer, and is preferably a block copolymer. The styrene-olefin copolymer is preferably at least one copolymer selected from the group consisting of a saturated copolymer obtained by polymerization 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 the unsaturated copolymer.

[0089] The polystyrene block constituting the styrene-olefin block copolymer becomes physical crosslinking points at the glass transition temperature or less and exhibits excellent rubber elasticity. The polyolefin block constituting the styrene-olefin block copolymer has fluidity at the glass transition temperature or more and contributes to easy processability. Preferred examples of the styrene-olefin block copolymer include a diblock type having the form of PS-PO and a triblock type having the form of PS-PO-PS. Herein, PS means polystyrene. PO means polyolefin. Examples of the styrene-olefin copolymer include: preferably, hydrogenated styrene-olefin copolymers; among them, more preferably, at least one copolymer selected from the group consisting of a styrene-ethylene/butylene-styrene block copolymer (hereinafter may be abbreviated as SEBS), a styrene-ethylene/propylene-styrene block copolymer (hereinafter may be abbreviated as SEPS), and a styrene-(ethylene-ethylene/propylene)-styrene block copolymer (hereinafter may be abbreviated as SEEPS); and still more preferably, SEBS.

[0090] The mass ratio of polyolefin in the blend 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 still more preferably 308 by mass or more and 50% by mass or less. Melt-spinning of single styrene-olefin copolymer causes many thread breakages, but melt-mixing of polyolefin improves the spinnability.

[0091] The mass ratio of all styrene residues to the mass of the styrene-olefin copolymer is 5% by mass or more and 50% by mass or less, preferably 10% by mass or more and 40% by mass, more preferably 108 by mass or more and 30% by mass or less, and still more preferably 10% by mass or more and 25% by mass or less. If the mass ratio of all styrene residues to the mass of the styrene-olefin copolymer is 5% by mass or more and 50% by mass or less, the number of benzene rings to which halogen groups are introduced is limited, and thus the amount of halogen groups can be suppressed, and the fragility of the nonwoven fabric can be suppressed, thereby further reducing the amount of fine particles generated. Although the amount of halogen groups is reduced, enough ligands can be introduced to adsorb biotoxic substances (in one example, endotoxin), and thus it is possible to reduce the number of ligands required for producing the fiber material for liquid purification, thereby allowing to reduce the cost of the fiber material for liquid purification. Herein, when the ligand-immobilized nonwoven fabric (nonwoven fabric for liquid purification) is made using a nonwoven fabric base material originally created by mixing a polymer containing halogen, halogen is interpreted to mean excluding the halogen in the polymer. In addition to endotoxin, the biotoxic substance includes causative substances of various diseases such as enterotoxin, bilirubin, abnormal cells such as blood cancer cells and white blood cells, immunogenic substances, excess biologically essential elements, proteins, lipids, bile acids, viruses, bacteria and their spores, endocrine disruptors, heavy metals (including iron), and amyloid B, the causative agent of Alzheimer's disease.

<Method for Producing Nonwoven Fabric Base Material>

[0092] The nonwoven fabric base material can be produced by any method as long as it is possible to form a nonwoven base material using a mixed fiber of polyolefin and the styrene-olefin copolymer. More preferred production methods are a melt blown method, a needle punch method, and an electrospinning method. Each of the above production methods will be explained below.

(1) Melt Blown Method

[0093] Polyolefin and a styrene-olefin copolymer are melt-mixed and flowed toward a drum by the force of air through an outlet lined with fine holes. This makes a nonwoven fabric consisting of fibers in which polyolefin and the styrene-olefin copolymer are mixed in a single fiber. Since no binder is used, a nonwoven fabric consisting only of the mixed resin fiber can be obtained.

(2) Needle Punch Method

[0094] The fibers consisting of a mixture of polyolefin and a styrene-olefin copolymer are stacked and made into thin multilayers, which are compressed using a machine equipped with needles to produce a nonwoven fabric. This method is a method of using needles to pull up the fibers and entangle the fibers.

(3) Electrospinning Method

[0095] This method is also referred to as an electrospinning method. The spinning apparatus includes a DC high-voltage power source, a spinneret, and a collector. Polyolefin and the styrene-olefin copolymer are melt-mixed, and the polymer solution is extruded through the spinneret to which a high voltage is applied. Each extruded polymer solution turns into fibers with nano-level fiber diameters, reaches a grounded collector, and becomes a nonwoven fabric.

[0096] The nonwoven fabric base material according to this embodiment can be produced using a production method other than the above, for example, an air-laid method, a spunbond method, or a wet method similar to papermaking.

<Fiber Material for Liquid Purification>

[0097] The fiber material for liquid purification according to this embodiment is obtained by introducing a ligand that interacts with a biotoxic substance into the above-described nonwoven fabric base material. Specifically, the fiber material for liquid purification is obtained by introducing a halogen-containing compound as a linker into the styrene residue of the styrene-olefin copolymer constituting the above-described nonwoven fabric, and further eliminating the halogen on the linker to allow the ligand to be supported. That is, the fiber material for liquid purification is obtained by introducing the halogen group-containing substituent into the styrene-olefin copolymer as a spacer, and replacing some of the halogen groups in the spacer with a ligand that interacts with a biotoxic substance.

[0098] The ligand has, relative to 1 g of dry mass of the fiber material for liquid purification, preferably more than 0 mol and 600 mol or less, more preferably 0.02 mol or more and 290 mol or less, still more preferably 0.02 mol or more and 15 mol or less, particularly more preferably 0.04 mol or more and 12.5 mol or less. The fiber material for liquid purification may contain a halogen because the linker containing a halogen is added to styrene during the production process. The halogen content in the fiber material for liquid purification is, relative to the mass of the fiber material for liquid purification, preferably more than 0 mol/g and 900 mol/g or less, more preferably more than 0 mol/g and 600 mol/g or less, still more preferably more than 0 mol/g and 290 mol/g or less, still more preferably more than 0 mol/g and 200 mol/g or less, still more preferably more than 0 mol/g and 150 mol/g or less, still more preferably more than 0 mol/g and 100 mol/g or less, and particularly more preferably more than 0 mol/g and 50 mol/g or less. Herein, when the ligand-immobilized nonwoven fabric (nonwoven fabric for liquid purification) is produced using a nonwoven fabric base material originally created by mixing a polymer containing halogen, halogen excludes the halogen in the polymer. This lower halogen content compared to conventional products reduces the number of times the user has to clean the product, making it easier to use.

[0099] The ligand that interacts with a biotoxic substance is, for example, derived from an amino acid, an oligopeptide, a peptide, a saccharide, an oligopolysaccharide, a polysaccharide, an antibody, a lipopolysaccharide, a lipid, a proteoglycan, a protein, an aptamer, and/or a polyelectrolyte, but is not limited thereto as long as it has one or more nucleophilic substituents that react with the halogen of the linker. Examples of the nucleophilic substituent include an amino group, an alkoxy group, a thiolate group, and an acetylide group. Exemplary ligands include tryptophan, L(.sup.+)-arginine, phenylalanine, monoethanolamine, ethylenediamine, heparin, an azide group, lactoferrin, and gelatin. The ligand preferably has an amino group capable of adsorbing endotoxin. The ligand is, for example, an antibiotic or a cationic polymer such as polylysine or polyethyleneimine. As the antibiotic, peptide compounds such as polymyxins and histatin are preferable, and among them, low molecular weight peptides are more preferable, and polymyxins are particularly preferable. Polymyxins include polymyxin A, polymyxin B1, polymyxin B2, polymyxin D1, polymyxin E1, and polymyxin E2. In addition, a salt represented by these sulfates and hydrochlorides can be used. As for the ligand, one of the above-described examples may be used singly, or two or more types may be used in combination. The ligand is supported on the styrene-olefin copolymer by chemical bonding between the nucleophilic substituent and the spacer.

<Method for Producing Fiber Material for Liquid Purification>

[0100] The fiber material for liquid purification according to this embodiment can be produced through the following halogenation step and ligand supporting step.

[0101] A method for producing the fiber material for liquid purification according to this embodiment is a method for producing any of the above-described fiber materials for liquid purification, comprising a halogenation step of contacting a halogen-containing compound with a nonwoven fabric base material to provide a halogenated nonwoven fabric, and a ligand supporting step of dehalogenating the halogenated nonwoven fabric to allow the ligand to be supported on the styrene-olefin copolymer. Each step will be explained in more detail below.

(1) Halogenation Step

[0102] In a container, a nonwoven fabric base material, 2-chloro-N-(hydroxymethyl) acetamide, which is an example of a halogen compound, paraformaldehyde, nitrobenzene, and concentrated sulfuric acid are charged and stirred to react the halogen-containing compound with the styrene residue in the styrene-olefin copolymer constituting the nonwoven fabric base material. Then, the nonwoven fabric is removed from the container and cleaned using distilled water and methanol. Thereafter, the nonwoven fabric is dried to obtain a chlorinated nonwoven fabric (an example of a halogenated nonwoven fabric, the same applies hereinafter) in which the halogen-containing compound is immobilized on styrene.

(2) Ligand Supporting Step

[0103] The above-described chlorinated nonwoven fabric and a pH adjusting agent are charged into a solution obtained by mixing the ligand or a salt thereof and distilled water in a container, and the mixture is stirred. Then, the nonwoven fabric is taken out of the container and cleaned with distilled water to remove unreacted ligands and free hydrochloric acid. Subsequent drying provides a ligand-supported nonwoven fabric. Through this step, the chloro group of the chlorinated nonwoven fabric is eliminated and becomes hydrochloric acid, and a ligand is bonded to the position of the chloro group. In this step, binding of a plurality of ligands can also be performed. For example, to immobilize another ligand Y on a nonwoven fabric on which a ligand X has been immobilized, the ligand Y is dissolved in distilled water to prepare a ligand Y aqueous solution, the ligand X-immobilized nonwoven fabric is added thereto, the solution is stirred for a predetermined period of time, and rinsing with distilled water multiple times and then drying, allowing to provide a nonwoven fabric with immobilized ligands X and Y. An example of the ligand X is heparin. An example of the ligand Y is lactoferrin.

<Cleaning Device>

[0104] A cleaning device according to an embodiment of the present invention is a device that includes the above-described fiber material for liquid purification. The cleaning device is, for example, a blood purifier. The fiber material for liquid purification is included inside the blood purifier as a fiber material for blood purification. Both the fiber material for blood purification and the blood purifier are autoclave resistant. Another example of the cleaning device includes a liquid cleaning device for purifying liquid pharmaceuticals or liquid pharmaceutical raw materials. Both the fiber material for liquid purification and the liquid cleaning device are autoclave resistant. Another example of the cleaning device includes a waste liquid cleaning device that prevents the discharge of biotoxic substances into the environment. The fiber material for liquid purification is included inside the waste liquid cleaning device as a fiber material for waste liquid purification. Both the fiber material for waste liquid purification and the waste liquid cleaning device are autoclave resistant.

[0105] FIG. 1 shows a longitudinal sectional view of a cleaning device according to an embodiment of the present invention.

[0106] A cleaning device 100 has, for example, the following structure. A container body 1 of the cleaning device 100 has a pipe 3 passed through a bottom 2 thereof and fixed by welding at a contact surface 4. An outlet 5 is provided at the top of the container body 1. An opening 6 and an inlet 7 are provided at both upper and lower ends of the pipe 3. The opening 6 is sealed by a stopper 9 provided on the partition plate 8. A flow path for guiding liquid is formed inside the pipe 3, and a large number of through holes 10 are provided in the peripheral wall. Between the partition plate 8 and an inner bottom surface 11 of the container body 1, a ligand-immobilized nonwoven fabric 12 is wrapped around the pipe 3 in multiple layers. A filter 13 is provided inside the outlet 5.

[0107] An example of using the cleaning device 100 is as follows. The liquid containing the biotoxic substance flows through the opening 7 through the flow path a1, passes through the flow path a2 inside the pipe, and is discharged from the through hole 10 in the radial direction. The liquid flows in the radial direction a3 through the multiple layers of the ligand-immobilized nonwoven fabric (corresponding to the fiber material for liquid purification) 12, then is purified, and passes through the gap a4 between the outermost layer of the nonwoven fabric 12 and the inner surface of the container body 1, and fine particles are removed by a filter 13. Thereby, the purified liquid is recovered from an outlet 5 (a5).

[0108] According to the above embodiment, it is possible to provide a fiber material for liquid purification, being inexpensive, capable of reducing cleaning, and suppressing the generation of fine particles, and a cleaning device comprising the same. In addition, according to a part of the above embodiment, it is possible to provide a fiber material for liquid purification, having excellent adsorption performance of the biotoxic components, and a cleaning device comprising the same.

EXAMPLES

[0109] Examples of the present invention will be described in detail using polymyxin immobilization as an example. The present invention is not limited to the following examples.

Experiment 1

(1) Production of Nonwoven Fabric

Production Example 1

[0110] There were mixed 60 parts by mass (6 kg) of a styrene-ethylene/butylene-styrene polymer (SEBS, product number MD1648, manufactured by Kraton Corporation) having 20% by mass of styrene residues and 80% by weight of ethylene/butylene residues, and 40 parts by mass (4 kg) of polypropylene (product number MOPLEN HP461X, manufactured by LyondellBasell Industries Holding B. V.), and the melt blown method with the device ALM-MB manufactured by AIKI Riotech Corporation was used to produce a spun and nonwoven fabric (length 3000 mm x width 250 mmthickness 0.3 mm). This nonwoven fabric is referred to as nonwoven fabric A. Measurement of the amount of chlorine in the nonwoven fabric A by combustion ion chromatography found less than 0.001 w/w % (0.2 mol/g).

(2) Chlorination of Nonwoven Fabric

Production Example 2

[0111] In a polypropylene container (50 mL), 0.214 g of 2-chloro-N-(hydroxymethyl) acetamide (product number BLDP-05742, manufactured by BLD Pharm), 0.011 g of paraformaldehyde (product number 168-20955, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 20 ml of nitrobenzene (product number 143-01706, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 1 ml of 95% concentrated sulfuric acid (product number 192-04696, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and 1 g of a nonwoven fabric A were charged, and the mixture was inversely stirred for 3 hours at room temperature of 24 C. Then, the nonwoven fabric was taken out from the container, cleaned with distilled water and methanol, and then the remaining cleaning liquid was removed by drying in a vacuum dryer at 85 C. to provide a chlorinated nonwoven fabric A. Measurement of the amount of chlorine in the nonwoven fabric by combustion ion chromatography found that the amount of chlorine was 0.151 w/w % (43 mol/g).

Production Example 3

[0112] The nonwoven fabric A was chlorinated to provide a chlorinated nonwoven fabric B under the same conditions as in Production Example 2 except that the amount of concentrated sulfuric acid was increased to 2 ml. Measurement of the amount of chlorine in the nonwoven fabric by combustion ion chromatography found that the amount of chlorine was 0.131 w/w % (37 mol/g).

Production Example 4

[0113] The nonwoven fabric A was chlorinated to provide a chlorinated nonwoven fabric C under the same conditions as in Production Example 3 except that the amount of concentrated sulfuric acid was increased to 15 ml. Measurement of the amount of chlorine in the nonwoven fabric by combustion ion chromatography found that the amount of chlorine was 0.096 w/w % (27 mol/g).

Production Example 5

[0114] In a Pyrex (R) container (50 mL), there were charged 0.214 g of 2-chloro-N-(hydroxymethyl) acetamide (same as Production Example 2), 0.011 g of paraformaldehyde (same as Production Example 2), 20 ml of nitrobenzene (same as Production Example 2), 2 mL of 95% concentrated sulfuric acid (same as Production Example 2), and 1 g of the nonwoven fabric A, and the mixture was stirred using a magnetic stirrer and reacted at room temperature of 24 C. Then, the nonwoven fabric was taken out, cleaned with distilled water and methanol, and the remaining cleaning liquid was removed by drying in a vacuum dryer at 85 C. to provide a chlorinated nonwoven fabric D. Measurement of the amount of chlorine in the nonwoven fabric by combustion ion chromatography found that the amount of chlorine was 0.095 w/w % (27 mol/g).

Production Example 6

[0115] In a Pyrex (R) container (50 mL), there were charged 0.214 g of 2-chloro-N-(hydroxymethyl) acetamide (same as Production Example 2), 0.011 g of paraformaldehyde (same as Production Example 2), 20 ml of nitrobenzene (same as Production Example 2), 2 ml of 95% concentrated sulfuric acid (same as Production Example 2), and 1 g of the nonwoven fabric A, and the mixture was stirred and reacted using a magnetic stirrer in a water bath at 24 C. Then, the nonwoven fabric was taken out, cleaned with distilled water and methanol, and then the remaining cleaning liquid was removed by drying in a vacuum dryer at 85 C. to provide a chlorinated nonwoven fabric E. Measurement of the amount of chlorine in the nonwoven fabric by combustion ion chromatography found that the amount of chlorine was 0.073 w/w& (21 mol/g).

Production Example 7

[0116] A chlorinated nonwoven fabric F was obtained under the same conditions as Production Example 6 except that the temperature in the water bath was set at 20 C. Measurement of the amount of chlorine in the nonwoven fabric by combustion ion chromatography found that the amount of chlorine was 0.039 w/w % (11 mol/g).

Production Example 8

[0117] A chlorinated nonwoven fabric G was obtained under the same conditions as Production Example 6 except that the temperature in the water bath was set at 14 C. Measurement of the amount of chlorine in the nonwoven fabric by combustion ion chromatography found that the amount of chlorine was 0.019 w/w % (5 mol/g).

Production Example 9

[0118] A chlorinated nonwoven fabric H was obtained under the same conditions as Production Example 6 except that the temperature in the water bath was set at 5 C. Measurement of the amount of chlorine in the nonwoven fabric by combustion ion chromatography found that the amount of chlorine was 0.011 w/w % (3 mol/g).

Production Example 9A

[0119] A chlorinated nonwoven fabric H was obtained under the same conditions as Production Example 6 except that the temperature in the water bath was set at 50 C. Measurement of the amount of chlorine in the nonwoven fabric by combustion ion chromatography found that the amount of chlorine was 0.52 w/w % (146 mol/g).

(3) Polymyxinization of Chlorinated Nonwoven Fabric

Example 1

[0120] In the polypropylene container used in Production Example 2, there was weighed 15 mg of polymyxin B sulfate (product number 1-800-364-9897, manufactured by Cayman Chemical Company), to which 15 ml of distilled water was added, and was dissolved. To the reaction solution, 1 g of the chlorinated nonwoven fabric B and 2 mg of magnesium oxide for pH adjustment (product number 131-00282, manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.) were charged, and the mixture was inversely stirred at room temperature of 25 C. for 2 hours to be reacted. Then, the nonwoven fabric was taken out, cleaned with hydrochloric acid and distilled water, and then dried in a blow dryer at 40 C. for 3 hours to provide a polymyxin-supported nonwoven fabric A.

Example 2

[0121] A polymyxin-supported nonwoven fabric B was obtained under the same conditions as in Example 1 except that the amount of polymyxin B sulfate was set to 1 mg.

Example 3

[0122] A polymyxin-supported nonwoven fabric C was obtained under the same conditions as in Example 1 except that the chlorinated nonwoven fabric G was used and the amount of polymyxin B sulfate was set to 1 mg.

Example 4

[0123] A polymyxin-supported nonwoven fabric D was obtained under the same conditions as in Example 1 except that the amount of polymyxin B sulfate was set to 0.05 mg.

Property Evaluation 1

[0124] Various properties of polymyxin-supported nonwoven fabrics A, B, C, and D were evaluated. As a comparative material, Toremixin PMX-20R manufactured by Toray Industries, Inc. was used. Toremixin PMX-20R by Toray Industries, Inc. does not have a non-woven fabric structure, is made of polypropylene coated with styrene in the form of a knitted fiber. For this reason, a lot of chlorine was contained.

(1) Amount of Polymyxin Added During Reaction

[0125] Table 1 shows the amount of polymyxin added when producing various polymyxin-supported nonwoven fabric samples.

TABLE-US-00001 TABLE 1 Sample A B C D Amount of polymyxin added 15 1 1 0.05 during reaction (mg/g-fiber)

(2) Fine Particle Measurement

[0126] Table 2 shows a comparison of the number of fine particles generated when the polymyxin-supported nonwoven fabric B and the comparative material were subjected to two types of treatments. The objects to be measured were 0.17 g of each of the polymyxin-supported nonwoven fabric B and the comparative material cut into 2 cm squares. Each sample was placed in a 50 ml vial and these were cleaned by rinsing them 10 times with 10 ml of physiological saline. As a result, fibrils generated during cutting were removed. Then, after drying each sample, 10 ml of physiological saline was added, and the mixture was inversely stirred for 2 hours using a rotator (rotation speed: 10 rpm). As another method, after drying each sample, 10 ml of physiological saline was added and ultrasonic cleaning (frequency: 40 kHz) was performed for 20 minutes. The samples treated by these two methods were then diluted and subjected to a particle counter (model number: HIAC 9703+, manufactured by Beckman Coulter, Inc. The same applies to subsequent fine particle measurements).

TABLE-US-00002 TABLE 2 Particle Stirring by rotator Ultrasonic cleaning treatment size Comparative Comparative (m) material B material B 1.2-1.5 211298 2149 1569357 9028 1.5-2.sup. 141616 3106 1033976 6235 2-3 49353 1200 345098 2157 3-5 72447 1679 508808 4502 5-10 47628 416 297329 2141 10-15 7878 55 51949 55 15-20 843 0 6757 0 20-25 874 39 580 63 25-30 0 8 580 0 30-35 0 0 0 0 35-40 0 0 0 71 40-45 0 0 0 0 45-50 0 0 294 0 50-100 0 0 0 24 100-150 0 0 0 0

[0127] As is clear from Table 2, in both cases of the two types of treatments, it was found that the sample B generated fewer fine particles than the comparative material.

(3) Chlorine Amount

[0128] Table 3 shows a comparison of the chlorine amounts of various samples A, B, C, D and the comparative material. The amount of chlorine was measured by combustion ion chromatography. Specifically, the sample was burned and sucked using a combustion-suction system (model number SQ-10) manufactured by Yanaco LID Co., Ltd., and separation and analysis were performed using an ion chromatography system (model number ICA2000) manufactured by DKK-TOA Corporation and a column (TSK-gel Super IC-Anion HS). The same applies to subsequent measurements of the amount of chlorine.

TABLE-US-00003 TABLE 3 Sample Comparative A B C D material Chlorine amount 0.1310 0.1310 0.0185 0.1310 8.62 before supporting of polymyxin (w/w %) Chlorine amount 0.1111 0.1033 0.0056 0.0883 8.62 after supporting of polymyxin and autoclaving (w/w %) Chlorine amount 37 37 5 37 2431 before supporting of polymyxin (mol/g) Chlorine amount 31 29 2 25 2431 after supporting of polymyxin and autoclaving (mol/g)

[0129] As is clear from Table 3, it was found that all of the samples A, B, C, and D contained less chlorine than the comparative material.

(4) Change in pH after Autoclaving

[0130] The sample B and comparative material of each 100 mg were cleaned with ion-exchanged water, then dried, and subjected to sterilization treatment (121 C., 20 min) in an autoclave (model number: HV-85IILV, manufactured by Hirayama Manufacturing Corporation. The same applies to subsequent autoclaves) in 10 ml of physiological saline. As a result of examining the change in pH of the physiological saline before and after sterilization, the pH of the physiological saline of the sample B changed from 7.2 to 6.9. The pH of the physiological saline of the comparative material changed from 7.2 to 3.7. The pH measuring device used was model number HI 2020-01, manufactured by Hanna Instruments, Inc. The same applies to subsequent pH measurements. From this result, it is considered that in the sample D, the pH change of the physiological saline was smaller and the amount of dechlorination was smaller than that of the comparative material. This result showed that the sample B has the possibility of significantly simplifying the rinsing step before use as compared with the comparative material.

(5) Adsorption Capacity of Endotoxin in Water

[0131] Table 4 shows the result of adsorption treatment of endotoxin (100 EU/ml20 ml) in water using 25 mg of various samples. The endotoxin adsorption capacity was measured by turbidimetric time analysis. For analysis, Limulus ES-2 Single Test Wako, manufactured by Fuji Film Wako Pure Chemical Industries, Ltd., was used as a reagent, and for measurement, Toxinometer ET-7000, manufactured by Fuji Film Wako Pure Chemical Industries, Ltd., was used. A similar method was used in subsequent examinations of adsorption capacity for endotoxin or other biotoxic substances. The removal rate (%) in the table is a value obtained by multiplying (blank concentrationmeasured concentration)/blank concentration by 100.

TABLE-US-00004 TABLE 4 Sample A B C D Comparative material Removal rate after 93 93 98 90 73 2 hours (%) Removal rate after 99 99 99 99 89 4 hours (%)

[0132] Each of the samples A, B, C, and D also showed a higher removal rate than the comparative material in the 2-hour adsorption test and the 4-hour adsorption test.

(6) Adsorption Capacity for Endotoxin in Human Serum

[0133] Table 5 shows the result of adsorption treatment of endotoxin (100 EU/ml3 ml) in human serum using 15 mg of various samples. The removal rate (%) in the table is a value obtained by multiplying (blank concentrationmeasured concentration)/blank concentration by 100.

TABLE-US-00005 TABLE 5 Sample A B C D Comparative material Removal rate after 59 57 58 57 28 20 minutes (%) Removal rate after 69 65 80 68 44 60 minutes (%)

[0134] Each of the samples A, B, C, and D also showed a higher removal rate than the comparative material in a 20-minute adsorption test and a 60-minute adsorption test.

Experiment 2

(1) Production of Nonwoven Fabric

Production Example 10

[0135] A styrene-ethylene/butylene-styrene polymer (SEBS, product number G1657, manufactured by Kraton Corporation) of 60 parts by mass (6 kg) having 10% by weight of styrene residues and 90% by weight of ethylene/butylene residues, and 40 parts by mass (4 kg) of polypropylene (product number PWH02N, manufactured by Sun Allomer Ltd.) were mixed, and the melt blown method with the device ALM-MB manufactured by AIKI Riotech Corporation was used to produce a spun and nonwoven fabric (length 3000 mm x width 250 mmthickness 0.3 mm). This nonwoven fabric is referred to as nonwoven fabric I. Measurement of the amount of chlorine in the nonwoven fabric I by combustion ion chromatography found less than 0.2 mol/g.

(2) Chlorination of nonwoven fabric

Production Example 11

[0136] In a polypropylene container (50 mL), 0.214 g of 2-chloro-N-(hydroxymethyl) acetamide (product number BLDP-05742, manufactured by BLD Pharm), 0.068 g of paraformaldehyde (product number 168-20955, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 20 mL of nitrobenzene (product number 143-01706, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 2 mL of 95% concentrated sulfuric acid (product number 192-04696, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and 1 g of the nonwoven fabric I were charged, and the mixture was inversely stirred for 3 hours at room temperature of 25 C. Then, the nonwoven fabric was taken out from the container, cleaned with distilled water and methanol, and then dried in a blow dryer at 40 C. for 3 hours to provide a chlorinated nonwoven fabric I.

(3) Polymyxinization of Chlorinated Nonwoven Fabric

Example 5

[0137] In a polypropylene container (50 mL), there was weighed 15 mg of polymyxin B sulfate (product number 1-800-364-9897, manufactured by Cayman Chemical Company), to which 15 mL of distilled water was added, and was dissolved. To the reaction solution, 1 g of the chlorinated nonwoven fabric I and 2 mg of magnesium oxide for pH adjustment (product number 131-00282, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were added, and the mixture was inversely stirred for 2 hours at room temperature of 25 C. to be reacted. Then, the nonwoven fabric was taken out, cleaned with hydrochloric acid and distilled water, and then dried in a blow dryer at 40 C. for 3 hours to provide a polymyxin-supported nonwoven fabric I.

Experiment 3

(1) Production of Nonwoven Fabric

Production Example 12

[0138] A styrene-ethylene/butylene-styrene polymer (SEBS, product number MD1648, manufactured by Kraton Corporation) of 60 parts by mass (6 kg) having 20% by weight of styrene residues and 80% by weight of ethylene/butylene residues and 40 parts by mass (4 kg) of polypropylene (product number PWH02N, manufactured by Sun Allomer Ltd.) were mixed, and the melt blown method with the device ALM-MB manufactured by AIKI Riotech Corporation was used to produce a spun and nonwoven fabric (length 3000 mmwidth 250 mmthickness 0.3 mm). This nonwoven fabric is referred to as nonwoven fabric J. Measurement of the amount of chlorine in the nonwoven fabric J by combustion ion chromatography found less than 0.2 mol/g.

(2) Chlorination of Nonwoven Fabric

Production Example 13

[0139] Chlorination was performed under the same conditions as in Production Example 11 except that 1 g of the nonwoven fabric J was added in place of 1 g of the nonwoven fabric I to provide a chlorinated nonwoven fabric J.

(3) Polymyxinization of Chlorinated Nonwoven Fabric

Example 6

[0140] Polymyxinization was performed under the same conditions as in Example 5 except that 1 g of the chlorinated nonwoven fabric J was used in place of 1 g of the chlorinated nonwoven fabric I to provide a polymyxin-supported nonwoven fabric J.

Experiment 4

(1) Production of Nonwoven Fabric

Production Example 14

[0141] A styrene-ethylene/propylene-styrene polymer (SEPS, product number Septon 2002, manufactured by Kuraray Co., Ltd.) of 60 parts by mass (6 kg) having 30% by weight of styrene residues and 70% by weight of ethylene/propylene residues and 40 parts by mass (4 kg) of polypropylene (product number PWH02N, manufactured by Sun Allomer Ltd.) were mixed, and the melt blown method with the device ALM-MB manufactured by AIKI Riotech Corporation was used to produce a spun and nonwoven fabric (length 3000 mmwidth 250 mmthickness 0.3 mm). This nonwoven fabric is referred to as nonwoven fabric K. Measurement of the amount of chlorine in the nonwoven fabric K by combustion ion chromatography found less than 0.2 mol/g.

(2) Chlorination of Nonwoven Fabric

Production Example 15

[0142] Chlorination was performed under the same conditions as in Production Example 11 except that 1 g of the nonwoven fabric K was added in place of 1 g of the nonwoven fabric I to provide a chlorinated nonwoven fabric K.

(3) Polymyxinization of Chlorinated Nonwoven Fabric

Example 7

[0143] Polymyxinization was performed under the same conditions as in Example 5 except that 1 g of the chlorinated nonwoven fabric K was used in place of 1 g of the chlorinated nonwoven fabric I to provide a polymyxin-supported nonwoven fabric K.

Experiment 5

(1) Production of Nonwoven Fabric

Production Example 16

[0144] A styrene-ethylene/butylene-styrene polymer (SEBS, product number Tuftec H1517, manufactured by Asahi Kasei Corporation) of 60 parts by mass (6 kg) having 43% by weight of styrene residues and 57% by weight of ethylene/butylene residues and 40 parts by mass (4 kg) of polypropylene (product number PWH02N, manufactured by Sun Allomer Ltd.) were mixed, and the melt blown method with the device ALM-MB manufactured by AIKI Riotech Corporation was used to produce a spun and nonwoven fabric (length 3000 mmwidth 250 mmthickness 0.3 mm). This nonwoven fabric is referred to as nonwoven fabric L. Measurement of the amount of chlorine in the nonwoven fabric L by combustion ion chromatography found less than 0.2 mol/g.

(2) Chlorination of Nonwoven Fabric

Production Example 17

[0145] Chlorination was performed under the same conditions as in Production Example 11 except that 1 g of the nonwoven fabric L was added in place of 1 g of the nonwoven fabric I to provide a chlorinated nonwoven fabric L.

(3) Polymyxinization of Chlorinated Nonwoven Fabric

Example 8

[0146] Polymyxinization was performed under the same conditions as in Example 5 except that 1 g of the chlorinated nonwoven fabric L was used in place of 1 g of the chlorinated nonwoven fabric I to provide a polymyxin-supported nonwoven fabric L.

Property Evaluation 2

[0147] Various properties of the polymyxin-supported nonwoven fabrics I, J, K, and L were evaluated. As a comparative material, Toremixin PMX-20R manufactured by Toray Industries, Inc. was used. In the property evaluation 2, conditions not described in particular are the same conditions as the property evaluation 1.

(1) Fine Particle Measurement

[0148] Tables 6 and 7 show a comparison of the number of fine particles generated when two types of treatments were applied to the polymyxin-supported nonwoven fabrics I, J, K, and L and the comparative material. The objects to be measured were four types of polymyxin-supported nonwoven fabrics cut into 2 cm squares and one type of comparative material. Each sample was placed in a 50 mL vial and cleaned by rinsing them 10 times with 10 mL of physiological saline. As a result, fibrils generated during cutting were removed. Then, after drying each sample, 10 mL of physiological saline was added, and the mixture was inversely stirred for 2 hours using a rotator (rotation speed: 10 rpm). As another method, after drying each sample, 10 mL of physiological saline was added and ultrasonic cleaning (frequency: 40 kHz) was performed for 20 minutes. The samples treated with these two methods were then diluted and submitted to a particle counter. Table 6 shows the result of the sample that was inversely stirred with a rotator, and Table 7 shows the result of the sample that was ultrasonically cleaned. As is clear from Tables 6 and 7, in both cases of the two types of treatments, each sample of Examples 5 to 8 was found to generate fewer fine particles than the comparative material.

TABLE-US-00006 TABLE 6 Example Example Example Example 5 6 7 8 Comparative Particle size Blank (I) (J) (K) (L) material 1.2 m or more 2376 1459 2337 13224 918 211298 and 1.5 m or less 1.5 m or more 306 494 2216 4494 94 141616 and 2 m or less 2 m or more 376 353 776 4682 24 49353 and 3 m or less 3 m or more 188 71 1086 2400 71 72447 and 5 m or less 5 m or more 47 118 365 612 0 47628 and 10 m or less 10 m or more 0 0 59 47 0 7878 and 15 m or less 15 m or more 0 0 4 24 0 843 and 20 m or less 20 m or more 0 0 24 0 0 874 and 25 m or less 25 m or more 0 0 8 24 0 0 and 30 m or less 30 m or more 0 0 0 0 0 0 and 35 m or less 35 m or more 0 0 0 0 0 0 and 40 m or less 40 m or more 0 0 0 0 0 0 and 45 m or less 45 m or more 0 0 0 0 0 0 and 50 m or less 50 m or more 0 0 4 0 0 0 and 100 m or less 100 m or more 47 0 0 0 0 0 and 150 m or less

TABLE-US-00007 TABLE 7 Example Example Example Example 5 6 7 8 Comparative Particle size Blank (I) (J) (K) (L) material 1.2 m or more 2635 6682 13788 452847 6565 1569357 and 1.5 m or less 1.5 m or more 565 2212 9906 123624 2447 1033976 and 2 m or less 2 m or more 376 1741 3529 129271 2565 345098 and 3 m or less 3 m or more 141 1106 6282 39341 1129 508808 and 5 m or less 5 m or more 24 282 2753 4424 212 297329 and 10 m or less 10 m or more 71 47 165 612 47 51949 and 15 m or less 15 m or more 0 24 0 94 71 6757 and 20 m or less 20 m or more 0 0 71 0 0 580 and 25 m or less 25 m or more 0 0 0 0 0 580 and 30 m or less 30 m or more 0 0 0 0 0 0 and 35 m or less 35 m or more 0 0 71 0 0 0 and 40 m or less 40 m or more 0 0 0 0 0 0 and 45 m or less 45 m or more 0 0 0 0 0 294 and 50 m or less 50 m or more 0 0 24 0 0 0 and 100 m or less 100 m or more 0 0 0 0 0 0 and 150 m or less

(2) Amount of Chlorine

[0149] Table 8 shows a comparison of the chlorine amounts of the polymyxin-supported nonwoven fabrics I, J, K, and L and the comparative material after autoclaving. The amount of chlorine was measured by combustion ion chromatography. As is clear from Table 8, each sample of Examples 5 to 8 was found to contain a smaller amount of chlorine than the comparative material.

TABLE-US-00008 TABLE 8 Exam- Exam- Exam- Exam- ple 5 ple 6 ple 7 ple 8 Comparative (I) (J) (K) (L) material Chlorine content 40 27 508 229 2431 [mol/g]
(3) Change in pH after Autoclaving

[0150] Table 9 shows the pH changes in physiological saline before and after the polymyxin-supported nonwoven fabrics I, J, and L and the comparative material were subjected to autoclave sterilization treatment in physiological saline. Each 100 mg of the polymyxin-supported nonwoven fabrics and the comparative material were cleaned with ion-exchanged water, dried, and then subjected to autoclave sterilization treatment (121 C., 20 min) in 10 mL of physiological saline. The physiological saline before and after sterilization was subjected to a pH meter. These results showed that the sample of each example had the possibility of greatly simplifying the rinsing step before use as compared with the comparative material.

TABLE-US-00009 TABLE 9 Example 5 Example 6 Example 8 Comparative (I) (J) (L) material Before autoclaving 7.2 7.2 7.2 7.2 After autoclaving 6.1 6.9 4.8 3.7

(4) Adsorption Capacity of Endotoxin in Water

[0151] Table 10 shows the result of adsorption treatment of endotoxin in water (100 EU/mL20 mL) on each 25 mg of polymyxin-supported nonwoven fabrics I, J, K and comparative material after autoclaving. The adsorption (%) in the table is a value obtained by multiplying (blank concentrationmeasured concentration)/blank concentration by 100. Adsorption may also be referred to as removal rate. As is clear from Table 10, the sample of each example was found to have higher adsorption capacity than the comparative material.

TABLE-US-00010 TABLE 10 Example 5 Example 6 Example 7 Comparative (I) (J) (K) material Adsorption of 99% 99% 79% 73% endotoxin in water

(5) Adsorption Capacity for Endotoxin in Human Serum

[0152] Table 11 shows the result of adsorption treatment of endotoxin in serum (100 EU/mL3 mL) on each 15 mg of the polymyxin-supported nonwoven fabric J and the comparative material after autoclaving. The adsorption (%) in the table is a value obtained by multiplying (blank concentrationmeasured concentration)/blank concentration by 100. Adsorption may also be referred to as removal rate. As is clear from Table 11, the sample of each example was found to have higher adsorption capacity than the comparative material.

TABLE-US-00011 TABLE 11 Example 6 Comparative (J) material Adsorption of endotoxin 58% 28%

Experiment 6

(1) Production of Nonwoven Fabric

Production Example 18

[0153] A styrene-ethylene/butylene-styrene polymer (SEBS, product number G1657, manufactured by Kraton Corporation) of 20 parts by mass (2 kg) having 10% by weight of styrene residues and 90% by weight of ethylene/butylene residues and 80 parts by mass (8 kg) of polypropylene (product number PWH02N, manufactured by Sun Allomer Ltd.) were mixed, and the melt blown method with the device ALM-MB manufactured by AIKI Riotech Corporation was used to produce a spun and nonwoven fabric (length 3000 mmwidth 250 mmthickness 0.3 mm). This nonwoven fabric is referred to as nonwoven fabric M. Measurement of the amount of chlorine in the nonwoven fabric M by combustion ion chromatography found less than 0.2 mol/g.

(2) Chlorination of Nonwoven Fabric

Production Example 19

[0154] In a polypropylene container (50 mL), 0.214 g of 2-chloro-N-(hydroxymethyl) acetamide (product number BLDP-05742, manufactured by BLD Pharm), 0.068 g of paraformaldehyde (product number 168-20955, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 20 mL of nitrobenzene (product number 143-01706, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 2 mL of 95% concentrated sulfuric acid (product number 192-04696, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and 1 g of the nonwoven fabric M were charged, and the mixture was inversely stirred for 3 hours at room temperature of 25 C. Then, the nonwoven fabric was taken out from the container, cleaned with distilled water and methanol, and then dried in a blow dryer at 40 C. for 3 hours to provide a chlorinated nonwoven fabric M.

(3) Polymyxinization of Chlorinated Nonwoven Fabric

Example 9

[0155] In a polypropylene container (50 mL), there was weighed 15 mg of polymyxin B sulfate (product number 1-800-364-9897, manufactured by Cayman Chemical Company), to which 15 mL of distilled water was added, and was dissolved. To the reaction solution, 1 g of the chlorinated nonwoven fabric M and 2 mg of magnesium oxide for pH adjustment (product number 131-00282, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were charged, and the mixture was inversely stirred for 2 hours at room temperature of 25 C. to be reacted. Then, the nonwoven fabric was taken out, cleaned with hydrochloric acid and distilled water, and then dried in a blow dryer at 40 C. for 3 hours to provide a polymyxin-supported nonwoven fabric M.

Experiment 7

(1) Production of Nonwoven Fabric

Production Example 20

[0156] A styrene-ethylene/butylene-styrene polymer (SEBS, product number MD1648, manufactured by Kraton Corporation) of 20 parts by mass (2 kg) having 20% by weight of styrene residues and 80% by weight of ethylene/butylene residues and 80 parts by mass (8 kg) of polypropylene (product number PWH02N, manufactured by Sun Allomer Ltd.) were mixed, and the melt blown method with the device ALM-MB manufactured by AIKI Riotech Corporation was used to produce a spun and nonwoven fabric (length 3000 mmwidth 250 mmthickness 0.3 mm). This nonwoven fabric is referred to as nonwoven fabric N. Measurement of the amount of chlorine in the nonwoven fabric N by combustion ion chromatography found less than 0.2 mol/g.

(2) Chlorination of Nonwoven Fabric

Production Example 21

[0157] Chlorination was performed under the same conditions as in Production Example 19 except that 1 g of the nonwoven fabric N was added in place of 1 g of the nonwoven fabric M to provide a chlorinated nonwoven fabric N.

(3) Polymyxinization of Chlorinated Nonwoven Fabric

Example 10

[0158] Polymyxinization was performed under the same conditions as in Example 9 except that 1 g of the chlorinated nonwoven fabric N was used in place of 1 g of the chlorinated nonwoven fabric M to provide a polymyxin-supported nonwoven fabric N.

Experiment 8

(1) Production of Nonwoven Fabric

Production Example 22

[0159] A styrene-ethylene/butylene-styrene polymer (SEBS, product number MD1648, manufactured by Kraton Corporation) of 90 parts by mass (9 kg) having 20% by weight of styrene residues and 80% by weight of ethylene/butylene residues and 10 parts by mass (1 kg) of polypropylene (product number PWH02N, manufactured by Sun Allomer Ltd.) were mixed, and the melt blown method with the device ALM-MB manufactured by AIKI Riotech Corporation was used to produce a spun and nonwoven fabric (length 3000 mmwidth 250 mmthickness 0.3 mm). This nonwoven fabric is referred to as nonwoven fabric O. Measurement of the amount of chlorine in the nonwoven fabric O by combustion ion chromatography found less than 0.2 mol/g.

(2) Chlorination of Nonwoven Fabric

Production Example 23

[0160] Chlorination was performed under the same conditions as in Production Example 19 except that 1 g of the nonwoven fabric O was added in place of 1 g of the nonwoven fabric M to provide a chlorinated nonwoven fabric O.

(3) Polymyxinization of Chlorinated Nonwoven Fabric

Example 11

[0161] Polymyxinization was performed under the same conditions as in Example 9 except that 1 g of the chlorinated nonwoven fabric O was used in place of 1 g of the chlorinated nonwoven fabric M to provide a polymyxin-supported nonwoven fabric O.

Experiment 9

(1) Production of Nonwoven Fabric

Production Example 24

[0162] A styrene-ethylene/butylene-styrene polymer (SEBS, product number MD1648, manufactured by Kraton Corporation) of 95 parts by mass (9.5 kg) having 20% by weight of styrene residues and 80% by weight of ethylene/butylene residues and 5 parts by mass (0.5 kg) of polypropylene (product number PWH02N, manufactured by Sun Allomer Ltd.) were mixed, and the melt-blown method with the device ALM-MB manufactured by AIKI Riotech Corporation was used to produce a spun and nonwoven fabric (length 3000 mmwidth 250 mmthickness 0.3 mm). This nonwoven fabric is referred to as nonwoven fabric P. Measurement of the amount of chlorine in the nonwoven fabric P by combustion ion chromatography found less than 0.2 mol/g.

(2) Chlorination of Nonwoven Fabric

Production Example 25

[0163] Chlorination was performed under the same conditions as in Production Example 19 except that 1 g of the nonwoven fabric P was added in place of 1 g of the nonwoven fabric M to provide a chlorinated nonwoven fabric P.

(3) Polymyxinization of Chlorinated Nonwoven Fabric

Comparative Example 1

[0164] Polymyxinization was performed under the same conditions as in Example 9 except that 1 g of the chlorinated nonwoven fabric P was used in place of 1 g of the chlorinated nonwoven fabric M to provide a polymyxin-supported nonwoven fabric P. The polymyxin-supported nonwoven fabric P had strong adhesion between the nonwoven fabrics and failed to be rolled up into a blood purification column, and failed to be used for the property evaluation.

Experiment 10

(1) Chlorination of Nonwoven Fabric

[0165] In a polypropylene container, 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 charged, 22.6 g of a nonwoven fabric consisting of styrene-olefin copolymer (product number MD1648 manufactured by Kraton Corporation:PP=9:1) was added, and the reaction was performed in shaking incubator at 25 C. and 160 rpm for 3 hours with stirring. Thereafter, cleaning was performed three times with 200 ml of distilled water and 6 times with 600 ml of methanol to remove residual nitrobenzene, and then cleaned three times with 500 ml of distilled water. Thereafter, drying was performed for 2 hours at 40 C. in a constant temperature blow dryer to provide a chlorinated nonwoven fabric Q into which chlorine groups were introduced.

Example 12

(2) Tryptophanization of Chlorinated Nonwoven Fabric

[0166] An attempt was made to immobilize L-tryptophan (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.) on the chlorinated nonwoven fabric Q in the following manner. In a polypropylene container, 45 ml of 1 wt % tryptophan aqueous solution was charged, 300 mg of the chlorinated nonwoven fabric Q and 6 mg of magnesium oxide for pH adjustment were charged, and the mixture was inversely stirred for 2 hours at room temperature of 25 C. to be reacted. Then, the nonwoven fabric was taken out, cleaned with hydrochloric acid and distilled water, and then dried in a blow dryer at 40 C. for 3 hours to provide a tryptophan-introduced nonwoven fabric. As shown in FIG. 2, the introduction of tryptophan was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the tryptophan-introduced fiber using ATR-FT-IR (Nicolet FT-IR of Thermo Fisher Scientific Inc.) with tryptophan spectrum on database.

Experiment 11

Example 13

L-Arginination of Chlorinated Nonwoven Fabric

[0167] An attempt was made to immobilize L(.sup.+)-arginine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) on the chlorinated nonwoven fabric Q in the following manner. In a polypropylene container, 45 ml of a 1 wt % arginine aqueous solution was charged, 300 mg of the chlorinated nonwoven fabric Q and 6 mg of magnesium oxide for pH adjustment were charged, and the mixture was inversely stirred at room temperature of 25 C. at around pH 9.4 for 2 hours to be reacted. Then, the nonwoven fabric was taken out, cleaned with hydrochloric acid and distilled water, and then dried in a blow dryer at 40 C. for 3 hours to provide an arginine-introduced nonwoven fabric. As shown in Table 12, measurement with SEM-EDS (model number: Miniscope TM3000, manufactured by Hitachi High-Technologies Corporation) on this nonwoven fabric confirmed introduction of N derived from arginine. Further, as shown in FIG. 3, the introduction of arginine was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the arginine-introduced fiber using ATR-FT-IR (Nicolet FT-IR of Thermo Fisher Scientific Inc.) with the arginine spectrum on database.

TABLE-US-00012 TABLE 12 Spectrum: Point Element AN Series Net unn. C norm. C Atom. C [wt. %] [wt. %] [at. %] Carbon 6 K-series 23516 74.02 74.02 77.62 Nitrogen 7 K-series 652 17.20 17.20 15.47 Oxygen 8 K-series 577 8.79 8.79 6.92 Chlorine 17 K-series 0 0.00 0.00 0.00 Total: 100.00 100.00 100.00

Experiment 12

Example 14

Phenylalanization of Chlorinated Nonwoven Fabric

[0168] An attempt was made to immobilize phenylalanine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) on the chlorinated nonwoven fabric Q in the following manner. In a polypropylene container, 25 ml of a 1 wt % phenylalanine aqueous solution was charged, 1 g of the chlorinated nonwoven fabric Q and 4 mg of magnesium oxide for pH adjustment were charged, and the mixture was inversely stirred at 160 rpm for 48 hours at 45 C. to be reacted. Then, the nonwoven fabric was taken out and cleaned three times with 30 ml of 0.1N hydrochloric acid and three times with 50 ml of distilled water, and then cleaned three times with 30 ml of 0.018% Triton solution. In addition, suction filtration cleaning using 200 ml of 0.018% Triton solution and suction filtration cleaning using 200 ml distilled water were performed, and drying was performed for 2 hours in a blow dryer at 40 C. to provide a phenylalanine-introduced nonwoven fabric. As shown in FIG. 4, the introduction of phenylalanine was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the phenylalanine-introduced fiber using ATR-FT-IR (Nicolet FT-IR of Thermo Fisher Scientific Inc.) with the phenylalanine spectrum on database.

Experiment 13

Example 15

Monoethanol Amination of Chlorinated Nonwoven Fabric

[0169] An attempt was made to immobilize monoethanolamine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) on the chlorinated nonwoven fabric Q in the following manner. This corresponds to the introduction of OH groups into the chlorinated nonwoven fabric. In a polypropylene container, 25 ml of a 1 wt % monoethanolamine aqueous solution was charged, 1 g of the chlorinated nonwoven fabric Q and 4 mg of magnesium oxide for pH adjustment were charged, and the mixture was inversely stirred at 160 rpm for 48 hours at 45 C. to be reacted. Then, the nonwoven fabric was taken out and cleaned three times with 30 ml of 0.1N hydrochloric acid and three times with 50 ml of distilled water, and then cleaned three times with 30 ml of 0.018% Triton solution. In addition, suction filtration cleaning using 200 ml of 0.018% Triton solution and suction filtration cleaning using 200 ml distilled water were performed, and drying was performed in a blow dryer at 40 C. for 2 hours to provide an OH group-introduced nonwoven fabric. As shown in FIG. 5, the introduction of OH groups was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the monoethanolamine-introduced fiber using ATR-FT-IR (Nicolet FT-IR of Thermo Fisher Scientific Inc.) with the monoethanolamine spectrum on database.

Experiment 14

Example 16

Ethylenediamination of Chlorinated Nonwoven Fabric

[0170] An attempt was made to immobilize ethylenediamine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) on the chlorinated nonwoven fabric Q in the following manner. This corresponds to the introduction of amino groups into the chlorinated nonwoven fabric. In a polypropylene container, 25 ml of a 1 wt % ethylenediamine aqueous solution was charged, 1 g of the chlorinated nonwoven fabric Q and 4 mg of magnesium oxide for pH adjustment were charged, and the mixture was inversely stirred at 160 rpm for 48 hours at 45 C. to be reacted. Then, the nonwoven fabric was taken out and cleaned three times with 30 ml of 0.1N hydrochloric acid and three times with 50 ml of distilled water, and then cleaned three times with 30 ml of 0.018% Triton solution. In addition, suction filtration cleaning using 200 ml of 0.018% Triton solution and suction filtration cleaning using 200 ml distilled water were performed, and drying was performed in a blow dryer at 40 C. for 2 hours to provide an amino group-introduced nonwoven fabric. As shown in FIG. 6, the introduction of amino groups was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the chlorinated fiber from the IR spectrum obtained from the ethylenediamine-introduced fiber using ATR-FT-IR (Nicolet FT-IR of Thermo Fisher Scientific Inc.) with the ethylenediamine on the database.

Experiment 15

Example 17

Heparinization of Chlorinated Nonwoven Fabric Using Ethylenediaminated Fiber

[0171] An attempt was made to immobilize heparin on the amino group-introduced nonwoven fabric obtained in Example 16 of Experiment 14 in the following manner. In a 15 ml polypropylene container, 10 mg of heparin treated with sodium periodate (dialdehyde heparin) was charged, and 10 ml of an aqueous hydrochloric acid solution with pH=4 was added to make a 0.1 wt& solution (approximately 200 units/ml). To this solution, 100 mg of the amino group-introduced nonwoven fabric obtained in Example 16 was charged. After reaction at 25 C. for 24 hours at around pH=4 (vortexing at 100 rpm), the mixture was thoroughly cleaned with distilled water and dried for 3 hours in a blow dryer at 40 C. to provide a heparin-immobilized nonwoven fabric. As shown in FIG. 7, the introduction of heparin was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the untreated fiber from the IR spectrum obtained from the heparin-introduced fiber using ATR-FT-IR (Nicolet FT-IR of Thermo Fisher Scientific Inc.) with the FT-IR spectrum of aldehyde heparin.

Experiment 16

Example 18

Azidization of Chlorinated Nonwoven Fabric

[0172] An attempt was made to immobilize azide groups on the chlorinated nonwoven fabric Q in the following manner. In a 15 ml polypropylene container, 100 mg of sodium azide was charged, and then 10 ml of distilled water was added to make a 1 wt & aqueous solution. The chlorinated nonwoven fabric Q was charged to this solution. After reaction at around pH=8 at 25 C. for 24 hours (vortexing at 100 rpm), the mixture was thoroughly cleaned with distilled water and dried for 3 hours in a blow dryer at 40 C. to provide an azidized nonwoven fabric. As shown in FIG. 8, the introduction of the azide group was confirmed by comparing the ATR-FT-IR measurement result of the obtained nonwoven fabric in the same manner as in Experiment 14 with the spectrum of sodium azide on the database.

Experiment 17

Example 19

Lactoferrinization with Heparinized Fiber of Chlorinated Nonwoven Fabric

[0173] A functional protein that interacts with heparin was immobilized on a nonwoven fabric via immobilized heparin to develop a functional adsorbent. The heparin-immobilized nonwoven fabric synthesized in Example 17 of Experiment 15 not only has improved blood compatibility, but also interacts with many functional molecules, and can be used as a base for a highly functional fiber. Heparin is known to have a strong interaction with lactoferrin. This immobilizes lactoferrin, whereby LPS trap, virus trap, electrostatic interaction with LDL, and the like are expected.

[0174] First, 100 mg of lactoferrin (derived from milk, Biochemical grade 129-04121, manufactured by Fujifilm Corporation) was dissolved in 10 ml of distilled water to prepare a 0.1 wt % lactoferrin aqueous solution (pale red color). Then, to this lactoferrin aqueous solution, 10 mg of the heparin-immobilized nonwoven fabric obtained in Example 17 was charged and immersed at room temperature for 4 hours while stirring at a speed of 40 rpm. After rinsing vigorously with 20 ml of distilled water five times using vortexing at 300 rpm, drying was performed at room temperature to provide a lactoferrin-heparin immobilized nonwoven fabric. As shown in FIG. 9, the introduction of lactoferrin was confirmed by comparing the difference spectrum obtained by subtracting the IR spectrum obtained from the heparin-introduced fiber from the IR spectrum obtained from the lactoferrin-introduced fiber using ATR-FT-IR (Nicolet FT-IR of Thermo Fisher Scientific Inc.) with the lactoferrin FT-IR spectrum.

Experiment 18

Example 20

[0175] Alkali treatment gelatinization of chlorinated nonwoven fabric

[0176] An alkali-treated gelatin was immobilized on the chlorinated nonwoven fabric Q in the following manner. As the gelatin, an alkali-treated beef bone gelatin (LET-N230) manufactured by Nitta Gelatin Inc. was used. In a polypropylene container, 15 ml of a 1.6 wt % alkali-treated gelatin aqueous solution was charged, 100 mg of the chlorinated nonwoven fabric Q and 2 mg of magnesium oxide for pH adjustment were charged, and the mixture was inversely stirred at around pH=9.4 at room temperature of 25 C. for 2 hours to be reacted. Then, the nonwoven fabric was taken out, cleaned with hydrochloric acid and distilled water, and then dried in a blow dryer at 40 C. for 3 hours to provide an alkali-treated gelatin-introduced nonwoven fabric. As shown in Table 13, SEM-EDS (model number: Miniscope TM3000, manufactured by Hitachi High-Technologies Corporation) measurement of this nonwoven fabric confirmed the introduction of N derived from gelatin. As shown in FIG. 10, measurement of changes in the concentration of nitrogen derived from gelatin on the outermost surface using XPS (model number: JPS-9010MC, manufactured by JEOL Ltd.) confirmed the introduction of nitrogen at the outermost surface.

TABLE-US-00013 TABLE 13 Spectrum: Point Element AN Series Net unn. C norm. C Atom. C [wt. %] [wt. %] [at. %] Carbon 6 K-series 522447 84.75 84.75 87.32 Nitrogen 7 K-series 5295 8.49 8.49 7.50 Oxygen 8 K-series 8276 6.64 6.64 5.13 Chlorine 17 K-series 2183 0.12 0.12 0.04 Total: 100.00 100.00 100.00

Experiment 19

Example 21

Acid Treatment Gelatinization of Chlorinated Nonwoven Fabric

[0177] An acid-treated gelatin was immobilized on the chlorinated nonwoven fabric Q in the following manner. As the gelatin, an acid-treated pork skin gelatin (LET-NP250) manufactured by Nitta Gelatin Inc. was used. In a polypropylene container, 15 ml of a 1.6 wt % acid-treated gelatin aqueous solution was charged, and 100 mg of the chlorinated nonwoven fabric Q and 2 mg of magnesium oxide for pH adjustment were charged. The mixture was inversely stirred at around pH=9.4 for 2 hours at room temperature of 25 C. to be reacted. Then, the nonwoven fabric was taken out, cleaned with hydrochloric acid and distilled water, and then dried in a blow dryer at 40 C. for 3 hours to provide an acid-treated gelatin-introduced nonwoven fabric. As shown in Table 14, SEM-EDS (model number: Miniscope TM3000, manufactured by Hitachi High-Technologies Corporation) measurement of this nonwoven fabric confirmed the introduction of N derived from gelatin. As shown in FIG. 11, measurement of changes in the concentration of nitrogen derived from gelatin on the outermost surface using XPS (model number: JPS-9010MC, manufactured by JEOL Ltd.) confirmed the introduction of nitrogen at the outermost surface.

TABLE-US-00014 TABLE 14 Spectrum: Point Element AN Series Net unn. C norm. C Atom. C [wt. %] [wt. %] [at. %] Carbon 6 K-series 192072 85.99 85.99 88.32 Nitrogen 7 K-series 1949 8.78 8.78 7.73 Oxygen 8 K-series 2223 5.03 5.03 3.87 Chlorine 17 K-series 1309 0.20 0.20 0.07 Total: 100.00 100.00 100.00

Property Evaluation 3

[0178] The properties of the various ligand-supported nonwoven fabrics of Examples 9 to 21 were evaluated. As a comparative material, Toremixin PMX-20R manufactured by Toray Industries, Inc. was used. In the property evaluation 3, conditions not described in particular are the same conditions as the property evaluation 1.

(1) Fine Particle Measurement

[0179] Tables 15 and 16 show a comparison of the number of fine particles generated when two types of treatments were applied to various ligand-supported nonwoven fabrics and the comparative material. The treatment of the measurement object and the measurement method were the same as in the property evaluation 2. Table 15 shows the result of the sample that was inversely stirred with a rotator, and Table 16 shows the result of the sample that was ultrasonically cleaned. As is clear from Tables 15 and 16, in both cases of the two types of treatments, it was found that the sample of each example produced fewer fine particles than the comparative material.

TABLE-US-00015 TABLE 15 Example Example Example Example. Example Example Comparative Particle size 9 10 12 14 15 16 material 1.2 m or more 2471 3153 193 67 0 20 211298 and 1.5 m or less 1.5 m or more 847 847 60 10 1.3 23 141616 and 2 m or less 2 m or more 847 706 143 0 77 37 49353 and 3 m or less 3 m or more 1318 424 100 0 13 33 72447 and 5 m or less 5 m or more 776 212 60 0 7 0 47628 and 10 m or less 10 m or more 306 47 30 20 3 0 7878 and 15 m or less 15 m or more 212 24 13 3 0 6 843 and 20 m or less 20 m or more 0 0 13 0 3 10 874 and 25 m or less 25 m or more 0 0 0 0 3 0 0 and 30 m or less 30 m or more 24 24 0 0 0 0 0 and 35 m or less 35 m or more 0 0 3 0 0 3 0 and 40 m or less 40 m or more 0 0 0 0 0 0 0 and 45 m or less 45 m or more 0 0 7 0 0 10 0 and 50 m or less 50 m or more 0 0 0 0 0 0 0 and 100 m or less 100 m or more 0 24 0 0 0 3 0 and 150 m or less

TABLE-US-00016 TABLE 16 Example Example Example Example Example Example Comparative Particle size 9 10 12 34 15 16 material 1.2 m.or more 13647 19553 1400 2967 3433 2473 1569357 and 1.5 m or less 1.5 m or more 4165 6776 417 997 1037 613 1033976 and 2 m or less 2 m or more 5365 9624 143 1153 1203 660 345098 and 3 m or less 3 m or more 1576 8729 353 407 753 507 508808 and 5 m or less 5 m or more 212 5459 213 257 267 220 297329 and 10 m or less 10 m or more 94 918 157 53 37 57 51949 and 15 m or less 15 m or more 47 282 50 57 33 40 6757 and 20 m or less 20 m or more 0 24 37 23 7 13 580 and 25 m or less 25 m or more 0 47 10 7 3 7 580 and 30 m or less 30 m or more 0 0 10 0 0 6 0 and 35 m or less 35 m or more 0 0 3 0 0 3 0 and 40 m or less 40 m or more 0 0 3 3 0 0 0 and 45 m or less 45 m or more 24 0 0 10 0 13 294 and 50 m or less 50 m or more 0 0 0 3 0 3 0 and 100 m or less 100 m or more 0 0 0 0 0 0 0 and 150 m or less

(2) Amount of Chlorine

[0180] Table 17 shows a comparison of the chlorine amounts of the polymyxin-supported nonwoven fabrics M, N, O and the comparative material after autoclaving. The amount of chlorine was measured by combustion ion chromatography. As is clear from Table 17, each sample of Examples 9 to 11 was found to contain a smaller amount of chlorine than the comparative material.

TABLE-US-00017 TABLE 17 Example 9 Example 10 Example 11 Comparative (M) (N) (O) material Chlorine content 2 4 876 2431 [mol/g]
(3) Change in pH after Autoclaving

[0181] Table 18 shows the pH changes in physiological saline before and after sterilizing various ligand-supported nonwoven fabrics and the comparative material by autoclaving in physiological saline. The treatment of the measurement object and the measurement conditions were the same as in the property evaluation 2. From this result, the sample of each example had smaller pH changes than the comparative materials. Therefore, the sample of each example showed the possibility of greatly simplifying the rinsing step before use.

TABLE-US-00018 TABLE 18 Before autoclaving After autoclaving Example 9 7.2 6.6 Example 10 7.2 6.7 Example 11 7.2 4.5 Example 12 7.2 4.9 Example 13 7.2 7.7 Example 14 7.2 4.0 Example 15 7.2 5.6 Example 16 7.2 8.1 Example 20 7.4 7.3 Example 21 7.4 7.2 Comparative 7.2 3.7 material

(4) Adsorption Capacity of Endotoxin in Water

[0182] Table 19 shows the result of measuring the amount of adsorption after 2 hours for the adsorption treatment in which each 5 mg of various ligand-supported nonwoven fabrics and the comparative material after autoclaving were immersed in 4 ml of ion-exchanged water adjusted to an endotoxin concentration of 100 EU/mL, while stirring at 37 C. and 10 rpm. The adsorption (%) in the table is a value obtained by multiplying (blank concentrationmeasured concentration)/blank concentration by 100.

TABLE-US-00019 TABLE 19 Adsorption after 2 hours Ligand (%) Example 9 Polymyxin 61 Example 10 Polymyxin 99 Example 11 Polymyxin 99 Example 12 Tryptophan 60 Example 15 Monoethanolamine 98 Example 16 Ethylenediamine 97 Example 17 Heparin 18 Example 19 Heparin-lactoferrin 91 Example 20 Alkali-treated gelatin 39 Example 21 Acid-treated gelatin 98 Comparative 73 material

[0183] In the nonwoven fabric into which amino acids had been introduced as ligands, the endotoxin adsorption mechanism was clearly observed. The nonwoven fabric on which tryptophan was immobilized, which had hydrophobic moieties and amino groups after immobilization, showed a relatively high endotoxin adsorption of about 60%. Considering this result, it has been estimated that endotoxin adsorption does not occur only due to charge, but multiple factors originating from the structure and chemical composition of the ligand are involved, particularly factors such as the charge portion, hydrophobic portion, and distance have a large influence on the strength of the interaction. It has been found that endotoxin can be adsorbed with high efficiency of 97% and 98% even in the nonwoven fabric made from low-molecular-weight compounds such as ethylenediamine and monoethanolamine that have been converted into amino groups and OH groups. This is because the introduced ligand is an extremely small molecule, and the hydrophobicity of the base fiber developed in the present invention and the charge caused by the introduced ligand are close to each other, thereby allowing the more efficient removal. This can be applied to the filter that inexpensively removes biotoxic substances from water.

[0184] It is also possible to introduce polysaccharide and glycoprotein ligands. As an example, the endotoxin removal capacity was compared between a heparin-immobilized nonwoven fabric and a nonwoven fabric introducing lactoferrin, which is known to have a strong interaction with heparin. Heparin has strong anticoagulant activity and has the great advantage of increased blood compatibility when removing biotoxic substances from the blood, but has a negative charge to induce electrostatic repulsion against negative charge of endotoxin, and thus the removal amount was as small as 18%. On the other hand, for the nonwoven fabric immobilized with lactoferrin, which is known to have a strong interaction with LPS, to immobilize heparin by a strong interaction, and to be positively charged under physiological conditions, it was confirmed that endotoxin was removed with a high efficiency of 91%. This can be a nonwoven fabric that can remove endotoxins, lipids, and the like from the blood due to the strong interaction of lactoferrin combined with free iron in the blood while maintaining heparin-based blood compatibility.

[0185] Regarding gelatin, which is a protein and is known to interact with cell adhesion scaffolds and MMP, endotoxin adsorption experiments were performed on nonwoven fabrics using gelatin produced by two different treatments as immobilized ligands. In the alkali-treated gelatin-immobilized nonwoven fabric, the isoelectric point of the immobilized alkali-treated beef bone gelatin was found approximately around pH=5, and was negatively charged in the neutral region of pH=7.4. Therefore, in an adsorption experiment of negatively charged LPS in water, the removal rate was only about 38.5% after 2 hours, resulting in a certain amount of LPS removed due to the influence of hydrophobic interactions. Around pH=7.4, positively charged LDL and the like are considered to be effectively adsorbed. On the other hand, in the nonwoven fabric with acid-treated gelatin immobilized, the isoelectric point of the immobilized pork skin acid-treated gelatin was found at approximately around pH=8 to 9, which is close to that of the raw material collagen, and was positively charged in the neutral region of pH=7.4. Therefore, in an adsorption experiment of negatively charged LPS in water, the removal rate was approximately 98% after 2 hours, confirming the effectiveness. Overall, as the ligand for adsorbing LPS, the ligand with positive charges and hydrophobic moieties showed a high removal rate.

(5) Adsorption Capacity for Proteins, Lipids, and Iron in Normal Serum

[0186] The following eight types of nonwoven fabrics were used as the ligand-supported nonwoven fabrics used in the test. [0187] Polymyxin-immobilized nonwoven fabric (Example 2) PMx 10.4 mg [0188] Tryptophan-immobilized nonwoven fabric (Example 12) TPF 10.3 mg [0189] Arginine-immobilized nonwoven fabric (Example 13) ALG 10.6 mg [0190] Phenylalanine-immobilized nonwoven fabric (Example 14) PHA 10.1 mg [0191] Ethylenediamine immobilized nonwoven fabric (Example 16) EDA 9.8 mg [0192] Heparin-immobilized nonwoven fabric (Example 17) HEP 9.9 mg [0193] Heparin-lactoferrin immobilized nonwoven fabric (Example 19) HEP-LF 10.2 mg [0194] Acid-treated gelatin-immobilized nonwoven fabric (Example 21) ATG 10.7 mg

[0195] Approximately 10 mg of each sample was cut into small pieces and added to a 5 ml glass tube previously, and the tube was primed with heparin saline and thoroughly wetted. Immediately before the experiment, the priming solution was removed using a pipette, and 2 ml of pig serum was added thereto at 37 C. Specifically, calcium chloride was added to the blood to activate the coagulation system, and 30 minutes later, the blood was centrifuged at 1200 G to collect the serum. At this point, 0.5 ml of untreated serum was collected into a control tube and used as a control serum for the test. Thereafter, 2 ml of serum was dispensed into test tubes for each of the 8 types of samples described above, and an adsorption experiment was performed at a shaking speed of 350 rpm using a shaker (manufactured by Bio-Rad Laboratories, Inc.) heated to 37 C. Sampling was performed 2 hours after the start of the adsorption experiment to obtain a serum test sample. The test items were total protein level, albumin level, iron level, total cholesterol level, free cholesterol level, ester cholesterol level, triglyceride level, LDL level, and HDL level. The test result is shown in Table 20. Adsorption experiments showed that lipids were adsorbed on nonwoven fabrics with heparin-lactoferrin, tryptophan, and acid-treated gelatin as ligands for total cholesterol value, free cholesterol value, ester cholesterol value, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol value, and the like.

TABLE-US-00020 TABLE 20 Data of adsorption of protein, lipid, and iron for normal pig serum Adsorption amount(%) TP % ALB % Fe % T-CHO % F-CHO % E-CHO TG % LDL-C % HDL-C % Tryptophan 4.6 9.1 5.4 5.1 7.1 4.7 7.7 6.7 6.7 Phenylalanine 3.1 6.1 2.7 2.6 0 3.1 3.8 4.4 3.3 Arginine 3.1 3 4.5 5.1 0 6.3 3.8 4.4 3.3 Heparin 4.6 3 3.6 3.8 0 4.7 3.8 4.4 3.3 Heparin-lactoferrin 6.2 6.1 5.4 9 7.1 9.4 7.7 8.9 6.7 Polymyxin 3.1 3 3.6 5.1 0 6.3 7.7 6.7 6.7 Ethylenediamine 4.6 6.1 4.5 6.4 0 7.8 7.7 8.9 6.7 Acid-treated gelatin 6.2 6.1 4.5 7.7 7.1 7.8 3.8 6.7 6.7 TP: Total amount of protein ALB: Albumin amount Fe: Iron T-CHO: Total cholesterol F-CHO: Free cholesterol E-CHO: Ester cholesterol TG: Neutral fat triglyceride LDL-C: Low density lipoprotein cholesterol HDL-C: High density lipoprotein cholesterol

(6) Adsorption Capacity for Bilirubin and Bile Acid in Normal Serum

[0196] Eight types of nonwoven fabrics used for examining (5) Adsorption capacity for proteins, lipids, and iron in normal serum were used in the test. In addition, control serum and serum test samples were produced under the same conditions as (5) Adsorption capacity of proteins, lipids, and iron in normal serum. Test items were total bilirubin level, direct bilirubin level, indirect bilirubin level, and total bile acid level. The test result is shown in Table 21.

[0197] As shown in Table 21, it was confirmed that tryptophan, lactoferrin, and acid-treated gelatin, which are positively charged and hydrophobic, have a removal capacity of about 8%. Bilirubin is a molecule with a negative charge, and the nonwoven fabric introduced with the arginine ligand, which is the most basic amino acid, was confirmed to have the capacity of adsorbing 33% of total bilirubin and almost 100% of indirect bilirubin, indicating that the fabric may be a useful adsorbent.

TABLE-US-00021 TABLE 21 Adsorption of bilirubin and bile acid (Comparison of control blood and increase/decrease value) Ligand T-BIL (%) D-BIL (%) I-BIL (%) TBA (%) Tryptophan 0 50 25 8 Phenylalanine 17 100 75 4 Arginine 33 100 100 4 Heparin 17 50 0 4 Heparin-lactoferrin 17 100 25 8 Polymyxin 0 100 50 4 Ethylenediamine 17 50 0 4 Acid-treated gelatin 0 100 50 8 T-BIL: Total bilirubin D-BIL: Direct bilirubin I-BIL: Indirect bilirubin TBL: Total bile acid

INDUSTRIAL APPLICABILITY

[0198] The present invention can be used for blood purification, purification of pharmaceuticals and raw material liquids thereof, waste liquid treatment, and the like.