Absorbent

Abstract

To provide a material capable of efficiently absorbing both a negatively charged cytokine and positively charged cytokine.SOLUTION: Provided is an adsorbent composed of a ligand containing cationic functional groups, a ligand containing anionic functional groups, and a hydrophobic polymer substrate, wherein the negative charge measured by a dye adsorption method is 0.01 to 0.10 mmol / g and the positive charge is 0.01 to 0.05 mmol / g.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an adsorbent material. [Background technology]

[0002] It is known that multiple cytokines are involved in inflammatory diseases (Non-Patent Document 1). Cytokines that play a role in inducing inflammation have various isoelectric points, and in blood, negatively charged cytokines that exhibit anionic properties and positively charged cytokines that exhibit cationic properties are mixed.

[0003] As an adsorption material for cytokine adsorption, Patent Document 1 discloses a semipermeable membrane for cytokine adsorption that has high adsorption capacity for both negatively charged cytokines and positively charged cytokines. This semipermeable membrane adsorbs positively charged cytokines by ionic bonds with a sulfonated polyarylene ether copolymer, and further discloses that it also has an adsorption capacity for negatively charged cytokines, although the specific mechanism of action is unclear.

[0004] Patent Document 2 discloses a carrier for blood purification, which is characterized in that it has a first layer containing an anionic polymer and a second layer containing a cationic polymer, and the first layer and the second layer are coated in that order. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2023-13070 A [Patent Document 2] JP 2023-81326 A [Non-patent literature]

[0006] [Non-Patent Document 1] Kany et al., Int. J. Mol. Sci., 2019, 20, 6008 Summary of the Invention [Problem to be solved by the invention]

[0007] Regarding the semipermeable membrane of Patent Document 1, the mechanism of action of adsorption of negatively charged cytokines is unclear, but it is presumed to be hydrophobic interaction. However, since the semipermeable membrane of Patent Document 1 does not have a cationic functional group, it is considered that it does not adsorb negatively charged cytokines by electrostatic interaction. Therefore, even if the cytokine is negatively charged, it is considered that the adsorption ability for highly hydrophilic cytokines is low.

[0008] Although the blood purification carrier of Patent Document 2 is described as having cytokine adsorption ability, an excessive amount of cationic polymer is layered on an anionic polymer, and cytokines are adsorbed by the positive charge that is not completely neutralized, so it is considered that the negative charge derived from the anionic polymer cannot contribute to cytokine adsorption. Furthermore, even when the layering amount is optimized, the negative charge derived from the anionic polymer and the positive charge derived from the cationic polymer are neutralized, so it is considered that positive and negative charges cannot coexist on the carrier surface that adsorbs cytokines.

[0009] Therefore, an object of the present invention is to provide a material capable of adsorbing both positively charged cytokines and negatively charged cytokines with high efficiency. [Means for solving the problem]

[0010] The inventors have conducted intensive research to solve the above-mentioned problems, and as a result have found that an adsorption material consisting of a ligand containing a cationic functional group, a ligand containing an anionic functional group, and a hydrophobic polymer base material, and having a negative charge amount of 0.01 to 0.10 mmol / g and a positive charge amount of 0.01 to 0.05 mmol / g as measured by a dye adsorption method, can adsorb both negatively charged cytokines and positively charged cytokines with high efficiency.

[0011] That is, the present invention provides the following (1) to (7). (1) An adsorption material comprising a ligand containing a cationic functional group, a ligand containing an anionic functional group, and a hydrophobic polymer base material, the material having a negative charge amount of 0.01 to 0.10 mmol / g and a positive charge amount of 0.01 to 0.05 mmol / g as measured by a dye adsorption method. (2) The adsorption material according to (1), wherein the ligand containing the cationic functional group is bound to the hydrophobic polymer substrate, and the ligand containing the anionic functional group is bound to the ligand containing the cationic functional group. (3) The adsorption material according to (1), wherein the ligand containing the anionic functional group is bound to the hydrophobic polymer substrate, and the ligand containing the cationic functional group is bound to the ligand containing the anionic functional group. (4) The adsorption material according to any one of (1) to (3), having a negative charge amount of 0.01 to 0.06 mmol / g and a positive charge amount of 0.01 to 0.03 mmol / g as measured by a dye adsorption method. (5) The adsorptive material according to any one of (1) to (4), wherein the ligand containing a cationic functional group is an ethyleneimine polymer, and the ligand containing an anionic functional group is an anionic polysaccharide. (6) The adsorption material according to any one of (1) to (5), which is for adsorbing cytokines. (7) The adsorption material according to any one of (1) to (6), which is for adsorbing interleukin-6 and / or interleukin-8. Effect of the Invention

[0012] The adsorptive material of the present invention is capable of adsorbing both negatively charged and positively charged cytokines with high efficiency. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] The present invention will be described in detail below.

[0014] The adsorption material of the present invention is an adsorption material consisting of a ligand containing a cationic functional group, a ligand containing an anionic functional group, and a hydrophobic polymer base material, and is characterized in that the amount of negative charge measured by a dye adsorption method is 0.01 to 0.10 mmol / g and the amount of positive charge is 0.01 to 0.05 mmol / g.

[0015] The "hydrophobic polymer substrate" is a substrate made of one or more hydrophobic polymers such as polyolefins (e.g., polyethylene, polypropylene), poly(aromatic vinyl compounds) (e.g., polystyrene), polyesters (e.g., polyethylene terephthalate and polybutylene terephthalate), and polysulfone. Among the hydrophobic polymers, polyolefins or poly(aromatic vinyl compounds) are preferred. The hydrophobic polymer substrate is not limited to a homopolymer made of one type of monomer, but may be a copolymer made of multiple types of monomers of the hydrophobic polymers, or a physically kneaded mixture of multiple hydrophobic polymers.

[0016] The term "ligand" refers to a chemical structure that is bound to a hydrophobic polymer substrate in order to exhibit adsorption performance for a substance to be adsorbed.

[0017] The term "ligand containing a cationic functional group" refers to a chemical structure having an amino group. Examples of the ligand containing a cationic functional group include polymers containing a cationic functional group such as ethyleneimine polymers, N-acetylethylenediamine, N-methyl-2,2'-diaminodiethylamine, and 1,2-bis(2-aminoethoxyethane). When the substance to be adsorbed is a cytokine, a polymer containing a cationic functional group is preferred as the ligand containing a cationic functional group, since a high density of cationic functional groups allows for highly efficient adsorption to the anionic sites of the cytokine.

[0018] The term "polymer containing a cationic functional group" refers to a polymer made of a monomer containing a cationic functional group, and examples thereof include a homopolymer of a monomer containing a cationic functional group and a copolymer made of a plurality of monomers containing a cationic functional group. In addition, as long as the polymer contains one or more monomers containing a cationic functional group, a copolymer with a monomer not containing a cationic functional group also falls under the category of polymer containing a cationic functional group. When the substance to be adsorbed is a cytokine, a high density of cationic functional groups allows for highly efficient adsorption to the anionic sites of the cytokine, and therefore the polymer containing a cationic functional group is preferably a homopolymer of a monomer containing a cationic functional group or a copolymer made of a plurality of monomers containing a cationic functional group.

[0019] "Ethyleneimine polymer" refers to ethyleneimine (CH 2 -CH 2 It is a compound having a repeating structure of —NH), and examples thereof include ethylenediamine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, polyethyleneimine, etc. If the ethyleneimine polymer is branched, it is considered that the mobility of the ligand decreases, so the ethyleneimine polymer is preferably linear.

[0020] The term "ligand containing an anionic functional group" refers to a chemical structure having at least one of a sulfonic acid group, a carboxyl group, and a phosphate group. Examples of the ligand containing an anionic functional group include polymers containing an anionic functional group, such as anionic polysaccharides such as dextran sulfate, heparin, and carboxymethyl dextran. When the substance to be adsorbed is a cytokine, a polymer containing an anionic functional group is preferred as the ligand containing an anionic functional group, since a high density of anionic functional groups allows for highly efficient adsorption to the cationic sites of the cytokine.

[0021] The term "polymer containing an anionic functional group" refers to a polymer made of a monomer containing an anionic functional group, and examples thereof include a homopolymer of a monomer containing an anionic functional group, and a copolymer made of a plurality of monomers containing an anionic functional group. In addition, if the polymer contains one or more monomers containing an anionic functional group, a copolymer with a monomer not containing an anionic functional group also falls under the category of polymer containing an anionic functional group. When the substance to be adsorbed is a cytokine, a high density of anionic functional groups allows for highly efficient adsorption to the cationic site of the cytokine, and therefore the polymer containing an anionic functional group is preferably a homopolymer of a monomer containing an anionic functional group, or a copolymer made of a plurality of monomers containing an anionic functional group.

[0022] As the mode of binding of the "ligand containing a cationic functional group", the "ligand containing an anionic functional group" and the "hydrophobic polymer substrate", the ligand containing a cationic functional group and the ligand containing an anionic functional group may each be independently bound to the hydrophobic polymer substrate, the ligand containing a cationic functional group may be bound to the hydrophobic polymer substrate, and the ligand containing a cationic functional group may be further bound to the ligand containing a cationic functional group, or the ligand containing an anionic functional group may be bound to the hydrophobic polymer substrate, and the ligand containing a cationic functional group may be further bound to the ligand containing an anionic functional group. From the viewpoint of highly efficient adsorption of the adsorption target substance, if the ligand containing a cationic functional group and the ligand containing an anionic functional group are each independently bound to the hydrophobic polymer substrate, the ligand containing a cationic functional group and the ligand containing an anionic functional group will form an ionic bond, and the adsorption performance for the adsorption target substance will be reduced. Therefore, it is preferable that the ligand containing a cationic / anionic functional group is bound to the hydrophobic polymer substrate, and the ligand containing a cationic / anionic functional group is further bound to the ligand containing a cationic / anionic functional group.

[0023] There are no particular limitations on the manner in which the ligand is bound to the hydrophobic polymer substrate, but from the viewpoint of the difficulty of release from the hydrophobic polymer substrate, it is preferable that the ligand is bound to the surface of the hydrophobic polymer substrate by a covalent bond or an ionic bond.

[0024] "Cytokines" are a group of proteins that are produced by various cells, including immune cells, in response to stimuli such as infection and trauma, and are released outside the cells to act. Examples of cytokines include interferon α, interferon β, interferon γ, interleukin-1 to 15, tumor necrosis factor-α, tumor necrosis factor-β, high mobility group box-1, erythropoietin, and monocyte chemotactic factor. Among cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and high mobility group box-1 are considered to be causative substances of inflammatory diseases.

[0025] A "positively charged cytokine" is a cytokine with an isoelectric point of 7.5 or higher, and examples thereof include IL-8 and interferon β.

[0026] "Negatively charged cytokines" are cytokines with an isoelectric point of 6.5 or less, and examples thereof include IL-6 and interleukin-12.

[0027] The adsorption material according to the present embodiment is preferably for adsorbing proteins, more preferably for adsorbing cytokines, and even more preferably for adsorbing IL-8 and / or IL-6, since IL-8 and IL-6 are major causative substances of inflammatory diseases.

[0028] The term "adsorbent material" refers to a material that can adsorb a substance to be adsorbed in a solution by contacting the solution, thereby reducing the concentration of the substance to be adsorbed in the solution.

[0029] The shape of the adsorbent material is not particularly limited, but a film shape, particle shape, or fiber shape is preferred, and a fiber shape is more preferred. Considering use in blood purification, a fiber shape with a large specific surface area, flexibly deformable, and excellent handleability, particularly an island-in-the-sea fiber shape, is preferred. Furthermore, as shapes obtained by processing the above-mentioned fiber shapes, fiber bundles, knitted fabrics, woven fabrics, and nonwoven fabrics are preferred, knitted fabrics, woven fabrics, and nonwoven fabrics with a large specific surface area and low flow path resistance are more preferred, and knitted fabrics and woven fabrics are even more preferred from the viewpoints of ease of filling with the adsorbent material and uniformity of the flow paths.

[0030] The "amount of negative charge measured by the dye adsorption method" is the amount of negative charge measured using toluidine blue O, a dye capable of binding 1:1 with an anionic functional group. The adsorption material is impregnated with a toluidine blue O solution, the toluidine blue O concentration in the solution is measured before and after the impregnation, and the amount of negative charge of the adsorption material is calculated based on the amount of toluidine blue O reduced calculated from the toluidine blue O concentration before and after the impregnation. When toluidine blue O is adsorbed to a hydrophobic polymer substrate, the amount of negative charge of the hydrophobic polymer substrate is calculated by subtracting the amount of negative charge of the hydrophobic polymer substrate to which the ligand is bound from the amount of negative charge of the hydrophobic polymer substrate.

[0031] The "positive charge amount measured by the dye adsorption method" is the positive charge amount measured using Acid Orange 7, a dye capable of binding 1:1 with cationic functional groups. The adsorption material is impregnated with an Acid Orange 7 solution, the concentration of Acid Orange 7 in the solution before and after the impregnation is measured, and the positive charge amount of the adsorption material is calculated based on the amount of decrease in Acid Orange 7 calculated from the concentration of Acid Orange 7 before and after the impregnation. When Acid Orange 7 is adsorbed to a hydrophobic polymer substrate, the positive charge amount of the adsorption material is calculated by subtracting the positive charge amount of the hydrophobic polymer substrate from the positive charge amount of the hydrophobic polymer substrate to which the ligand is bound.

[0032] The amount of negative charge and the amount of positive charge measured by the dye adsorption method generally reflect the amount of anionic functional groups and the amount of cationic functional groups contained in the ligand. On the other hand, when the anionic functional groups and the cationic functional groups contained in the ligand are neutralized by ionic bonds, it is considered that the dye is difficult to adsorb to the functional groups neutralized by ionic bonds. Furthermore, cytokines, like dyes, are considered to be difficult to bind to functional groups neutralized by ionic bonds, so although the detailed mechanism is unknown, the amount of negative charge and the amount of positive charge calculated by the dye adsorption method are considered to reflect the cytokine adsorption performance.

[0033] From the viewpoint of highly efficient adsorption of the adsorption target substance, the amount of negative charge of the adsorption material measured by the dye adsorption method is preferably 0.01 to 0.10 mmol / g and the amount of positive charge is preferably 0.01 to 0.05 mmol / g, and more preferably 0.01 to 0.06 mmol / g and 0.01 to 0.05 mmol / g. When the adsorption target substance is a cytokine, although the detailed mechanism is unknown, it is considered that if the adsorption material has both negative and positive charges, it can bind to both the anionic and cationic sites of the cytokine, and highly efficient cytokine adsorption can be achieved.

[0034] The cytokine adsorption performance of the adsorbent material can be measured, for example, by impregnating the adsorbent material with fetal bovine serum (FBS) in which cytokines are dissolved, measuring the cytokine concentration in the FBS before and after impregnation, and calculating the cytokine removal rate from the cytokine concentrations before and after impregnation. The temperature during impregnation is not particularly limited as long as it is within the range in which the cytokines are physiologically active, and is, for example, 34°C to 44°C.

[0035] The concentration of a cytokine can be measured, for example, by reacting a cytokine detection reagent with a liquid containing the cytokine and measuring the amount of the cytokine bound to the reagent, using an enzyme-linked immunosorbent assay (ELISA).

[0036] The present invention is also characterized by providing a blood purifier comprising the above-mentioned adsorption material.

[0037] A "blood purifier" refers to a product that contains at least a portion of a medical material with the purpose of circulating blood outside the body and removing waste products and harmful substances from the blood. Examples of such a product include an artificial kidney module and an extracorporeal circulation column.

[0038] The present invention also provides a purification material for a biological agent, comprising the above-mentioned adsorbent material. EXAMPLES

[0039] The adsorption material of the present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0040] (Preparation of Fiber A) Using a spinneret with an extrusion hole designed to produce a fiber cross section with 256 island components in the sea component, polystyrene was used for the sea component and polypropylene for the island components. Melt spinning was performed so that the extrusion ratio of the sea component and the island components was 50:50 by volume, to obtain Fiber A, which was a bundle of 36 sea-island composite fibers, each with a fineness of 3dex (the total fineness of Fiber A was 108dex).

[0041] (Production of knitted fabric A) Fiber A was used for knitting using a cylindrical knitting machine (boiler diameter: 7 inches, number of needles: 480, needle density: 8.6 / cm) to obtain knitted fabric A.

[0042] (Preparation of adsorption material A) A reaction solution was prepared by mixing, stirring, and dissolving 46 wt% nitrobenzene, 46 wt% sulfuric acid, 1 wt% paraformaldehyde, and 7 wt% N-methylol-α-chloroacetamide at 10°C or less. 1.0 g of knitted fabric A was immersed in 40 mL of the reaction solution cooled to 5°C, and reacted for 2 hours while maintaining the temperature of the reaction solution at 5°C. Thereafter, knitted fabric A was removed from the reaction solution and immersed and washed in 40 mL of nitrobenzene. Next, knitted fabric A was removed and immersed and washed in methanol to obtain adsorbent material A.

[0043] (Preparation of adsorption material B) Diethylenetriamine and triethylamine were dissolved in 500 mL of DMSO to give a concentration of 20 mM and 200 mM, respectively, and 10 g of adsorbent A was immersed in the solution and reacted for 3 hours at 40° C. Then, adsorbent A after the reaction was removed from the reaction solution and immersed and washed in 500 mL of DMSO, then in 500 mL of methanol, and further in 500 mL of distilled water to obtain adsorbent B.

[0044] (Preparation of adsorption material C) Adsorbent material C was obtained by carrying out the same procedure as for producing adsorbent material B, except that 20 mM diethylenetriamine was replaced with 6 mM tetraethylenepentamine.

[0045] (Preparation of Adsorbent Material D) Adsorbent material D was obtained by carrying out the same procedure as for producing adsorbent material B, except that 20 mM diethylenetriamine was replaced with 12 mM tetraethylenepentamine.

[0046] (Preparation of adsorption material E) Adsorbent material E was obtained by carrying out the same procedure as for producing adsorbent material B, except that 20 mM diethylenetriamine was replaced with 20 mM tetraethylenepentamine.

[0047] (Preparation of adsorption material F) Adsorbent material F was obtained by carrying out the same procedure as for producing adsorbent material B, except that 20 mM diethylenetriamine was replaced with 5 mM polyethyleneimine having a molecular weight of 600.

[0048] (Preparation of adsorption material G) 1 g of adsorbent B was immersed in a reaction solution in which dextran sulfate sodium with a molecular weight of 5000 was dissolved in 20 mL of distilled water to a concentration of 1 wt%, and irradiated with γ-rays of 25 kGy. Then, adsorbent B was taken out of the dextran sulfate sodium solution and washed with distilled water to obtain adsorbent G.

[0049] (Preparation of adsorption material H) Adsorbent material H was obtained by carrying out the same operations as those for producing adsorbent material G, except that adsorbent material B was changed to adsorbent material D.

[0050] (Preparation of Adsorbent Material I) Adsorbent material I was obtained by carrying out the same operations as those for producing adsorbent material G, except that adsorbent material B was changed to adsorbent material E.

[0051] (Preparation of adsorption material J) Adsorbent material J was obtained by carrying out the same operations as for the preparation of adsorbent material I, except that the concentration of dextran sodium sulfate was changed from 1 wt % to 0.1 wt %.

[0052] (Preparation of adsorption material K) Adsorbent material K was obtained by carrying out the same operations as those for producing adsorbent material G, except that adsorbent material B was changed to adsorbent material F.

[0053] (Preparation of adsorbent material L) 1.0 g of adsorbent E was immersed in a reaction solution in which sodium carboxymethyl dextran with a molecular weight of 5000 was dissolved in 20 mL of distilled water to a concentration of 1 wt%, and 1.4 g of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride n-hydrate was added and reacted by stirring for 24 hours at 30° C. Thereafter, the adsorbent E after the reaction was removed from the reaction solution, and 50 mL of a 6 M aqueous sodium hydroxide solution was added to 1.0 g of the adsorbent E after the reaction, and the mixture was stirred at 25° C. for 30 minutes, followed by immersion washing in distilled water to obtain adsorbent L.

[0054] (Preparation of Adsorption Material M) 10 g of adsorbent material A was placed in 100 mL of 6 M hydrochloric acid and hydrolyzed at 120° C. for 24 hours. Next, adsorbent material A was removed from the hydrolyzed solution and immersed and washed in distilled water. After that, adsorbent material A after hydrolysis was placed in a reaction solution in which sodium dextran sulfate with a molecular weight of 5000 was dissolved in 20 mL of distilled water to a concentration of 1 wt%, and irradiated with γ-rays of 25 kGy. Then, adsorbent material A was removed from the reaction solution and immersed and washed in distilled water to obtain adsorbent material M.

[0055] (Preparation of adsorbent material N) 10 g of adsorbent material C was immersed in a reaction solution prepared by dissolving 2-mercaptoethanesulfonic acid and sodium hydroxide in 500 mL of distilled water to a concentration of 20 mM and 10 mM, respectively, and reacted for 3 hours at 40° C. After that, the adsorbent material C after the reaction was removed from the reaction solution and immersed and washed in 500 mL of distilled water to obtain adsorbent material N.

[0056] (Measurement of negative charge) 1 mL of 0.1 mol / L phosphate buffer prepared so that the concentration of toluidine blue O was 25 μg / mL was added to 2 mg of the adsorption material, and the mixture was mixed by rotating with a rotator at 25 ° C. for 1 hour. The concentration of toluidine blue O was measured before and after impregnation, and the negative charge amount was calculated from the amount of toluidine blue O reduced before and after impregnation. The concentration of toluidine blue O was obtained by measuring the absorbance of the toluidine blue O solution at a wavelength of 630 nm using a microplate reader Spectra Max M5 (Molecular Devices). The negative charge amount was calculated from the obtained concentration of toluidine blue O using the following formula (1), and the value rounded off to the fourth decimal place was used. Amount of negative charge (mmol / g) = {Concentration of toluidine blue O before impregnation (mmol / L) - Concentration of toluidine blue O after impregnation (mmol / L)} × Amount of solution (L) / Weight of adsorbent material (g) ··· Equation (1)

[0057] (Measurement of positive charge) 1 mL of 0.1 mol / L phosphate buffer prepared so that the concentration of Acid Orange 7 was 25 μg / mL was added to 2 mg of the adsorption material, and the mixture was mixed by rotating with a rotator at 25 ° C for 1 hour. The concentration of Acid Orange 7 was measured before and after impregnation, and the amount of positive charge was calculated from the amount of Acid Orange 7 decreased before and after impregnation. The concentration of Acid Orange 7 was obtained by measuring the absorbance of the Acid Orange 7 solution at a wavelength of 482 nm using a microplate reader Spectra Max M5 (Molecular Devices). The amount of positive charge was calculated from the obtained concentration of Acid Orange 7 using the following formula (2), and the value rounded off to the fourth decimal place was used. Amount of positive charge (mmol / g) = {Concentration of Acid Orange 7 before impregnation (mmol / L) - Concentration of Acid Orange 7 after impregnation (mmol / L)} × Amount of solution (L) / Weight of adsorbent material (g) ··· Equation (2)

[0058] (Measurement of IL-8 adsorption rate) 4 mg of the adsorbent material was placed in a polypropylene container. 5 mL of FBS prepared so that the IL-8 concentration was 2000 pg / mL was added to this container. After mixing by inversion for 24 hours in a 37°C incubator, the IL-8 concentration in the FBS was measured by ELISA. A Human CXCL8 / IL-8 Quantikine ELISA Kit (R&D System) was used for the measurement. The IL-8 adsorption rate was calculated from the IL-8 concentrations before and after mixing by inversion using the following formula (3), and the value was rounded off to the nearest whole number. IL-8 adsorption rate (%) = {IL-8 concentration before mixing (pg / mL) - IL-8 concentration after mixing (pg / mL)} / IL-8 concentration before mixing (pg / mL) × 100 Equation (3)

[0059] (Measurement of IL-6 adsorption rate) 40 mg of the adsorbent material was placed in a polypropylene container. 5 mL of FBS, which had been prepared so that the IL-6 concentration was 2000 pg / mL, was added to this container. After mixing by inversion for 24 hours in a 37°C incubator, the IL-6 concentration in the FBS was measured by ELISA. A Human IL-6 Quantikine ELISA Kit (R&D Systems) was used for the measurement. The IL-6 adsorption rate was calculated from the IL-6 concentrations before and after mixing by inversion using the following formula (4), and the value was rounded off to the nearest whole number. IL-6 adsorption rate (%) = {IL-6 concentration before mixing (pg / mL) - IL-6 concentration after mixing (pg / mL)} / IL-6 concentration before mixing (pg / mL) × 100 ··· Equation (4)

[0060] (Examples 1 to 6) The amount of negative charge, the amount of positive charge, the IL-8 adsorption rate, and the IL-6 adsorption rate were measured for the adsorption materials G to L. The results are shown in Table 1.

[0061] (Comparative Examples 1 to 4) The amount of negative charge, the amount of positive charge, the IL-8 adsorption rate, and the IL-6 adsorption rate were measured for the adsorptive materials A, E, M, and N. The results are shown in Table 1.

[0062] [Table 1]

[0063] The results of Examples 1 to 6 in Table 1 reveal that an adsorption material having a negative charge amount of 0.01 to 0.10 mmol / g and a positive charge amount of 0.01 to 0.05 mmol / g can highly efficiently adsorb both IL-8, a negatively charged cytokine, and IL-6, a positively charged cytokine.

[0064] From the results of Comparative Example 3 in Table 1, it was revealed that the adsorption rate of IL-8, which is a positively charged cytokine, was low in the adsorption material in which the negative charge amount was 0.01 to 0.10 mmol / g, as in Examples 1 to 6, but the positive charge amount was not 0.01 to 0.05 mmol / g. In other words, it was revealed that by having a certain amount of positive charge as well as a certain amount of negative charge, the positively charged cytokine can also be adsorbed with high efficiency. [Industrial Applicability]

[0065] The adsorption material of the present invention can be suitably used for adsorbing cytokines, and can be utilized as an adsorption material to be filled in a blood purifier for treating inflammatory diseases, or as a purification material for biological preparations.

Claims

1. The present invention comprises a ligand including a cationic functional group, a ligand including an anionic functional group, and a hydrophobic polymer substrate, The negative charge amount measured by a dye adsorption method is 0.01 to 0.10 mmol / g, and the positive charge amount is 0.01 to 0.05 mmol / g. Adsorption material.

2. 2. The adsorptive material of claim 1, wherein the ligand containing a cationic functional group is bound to the hydrophobic polymeric substrate and the ligand containing an anionic functional group is bound to the ligand containing a cationic functional group.

3. 2. The adsorptive material of claim 1, wherein the ligand containing an anionic functional group is bound to the hydrophobic polymeric substrate and the ligand containing a cationic functional group is bound to the ligand containing an anionic functional group.

4. The adsorptive material according to any one of claims 1 to 3, wherein the amount of negative charge measured by a dye adsorption method is 0.01 to 0.06 mmol / g and the amount of positive charge measured by a dye adsorption method is 0.01 to 0.03 mmol / g.

5. The adsorptive material according to any one of claims 1 to 4, wherein the ligand containing a cationic functional group is an ethyleneimine polymer, and the ligand containing an anionic functional group is an anionic polysaccharide.

6. The adsorptive material according to any one of claims 1 to 5, which is for adsorbing cytokines.

7. The adsorptive material according to any one of claims 1 to 6, which is for adsorbing interleukin-6 and / or interleukin-8.

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