Patent Application
20250032694
The present disclosure relates to an adsorbent material, an adsorbent sheet, a separation membrane, an artificial dialysis machine, and a production method.
The number of patients with renal disease is on an increasing trend year by year, and according to the statistics of the Japanese Society for Dialysis Therapy, the number of chronic dialysis patients has increased by approximately 17% from 2010 to 2020. When the renal function decreases due to renal disease, the disease-causing substances accumulate in the blood, and as a result, uremia, electrolyte imbalance, autoimmune disease, and the like can be caused. In order to treat such various symptoms associated with renal disease, a hemodialysis type renal function substitute or the like that removes a disease-causing substance to the outside of the body is used.
In the adsorbent material described in Non-patent Document 1, the adsorbate is limited to certain materials.
One object of the present disclosure is to provide a novel adsorbent material used for adsorbing a wider range of adsorbates as compared to Non-patent Document 1. Another object of the present disclosure is to provide an adsorbent sheet using such an adsorbent material, a separation membrane, an artificial dialysis machine, and a method for producing such an adsorbent.
The adsorbent material of the present disclosure comprises two-dimensional particles having one or plural layers, wherein the one or plural layers comprise a layer body represented by:
The present disclosure provides a novel adsorbent material used for adsorbing a wider range of adsorbates as compared with Non-patent Document 1. In addition, the present disclosure provides an adsorbent sheet using an adsorbent material used for adsorbing a wider range of adsorbates than in Non-patent Document 1, a separation membrane, an artificial dialysis machine, and a method for producing such an adsorbent material.
The adsorbent material of the present disclosure is used for adsorbing a disease-causing substance, and the adsorbent material includes two-dimensional particles having one or plural layers, wherein the one or plural layers comprise a layer body represented by a composition formula below:
MmXn
The present disclosure provides an adsorbent material capable of adsorbing various adsorbates, and particularly, provides an adsorbent material capable of adsorbing a disease-causing substance. Although the present disclosure should not be construed as being limited to a specific theory, the reason why the adsorbent material of the present disclosure adsorbs various adsorbates is considered as follows.
The two-dimensional particles contained in the adsorbent material of the present disclosure are particles of a layered material also referred to as MXene, and have one or more modifier or terminal T (T is at least one selected from the group consisting of a hydroxyl group, a fluorine atom, a chlorine atom, an oxygen atom, and a hydrogen atom) on the surface of the layer body represented by MmXn. With such a configuration, a charged site presents in the layer included in the two-dimensional particle, and the layer surface of the two-dimensional particle usually is negatively charged. In addition, the end surface of the two-dimensional particle (the peripheral edge of the layer of the two-dimensional particle) is usually positively charged. Therefore, when viewed as the entire two-dimensional particle, the positively charged adsorbate (for example, a cation or the like) tends to be adsorbed between the layers, and the negatively charged adsorbate (for example, an anion or the like) tends to be adsorbed on the end face of the layer.
The inventors of the present disclosure have studied an adsorbates which the two-dimensional particles are capable of adsorbing, and found that the two-dimensional particles adsorb a relatively high molecular weight compound such as a protein in addition to the positively or negatively charged adsorbent.
The two-dimensional particle may be understood as a layered material or layered compound, also denoted “MmXnTs”, wherein s is any number, and conventionally x or z may be used instead of s. Typically, n can be 1, 2, 3, or 4, but is not limited thereto.
In the present disclosure, the layer may be referred to as an MXene layer, and the two-dimensional particle may be referred to as an MXene two-dimensional particle or an MXene particle.
In the above formula of MXene, M is at least one selected from the group consisting of Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, and Mn, and preferably contains at least Ti, and more preferably contains at least one selected from the group consisting of Ti, V, Cr, and Mo, and contains at least Ti.
The ratio of Ti atoms in M may be preferably not less than 50 atom % and not more than 100 atom % or less, more preferably not less than 70 atom % and not more than 100 atom % or less, and still more preferably not less than 90 atom % and not more than 100 atom % or less.
MXenes whose above formula MmXn is expressed as below are known:
Sc2C, Ti2C, Ti2N, Zr2C, Zr2N, Hf2C, Hf2N, V2C, V2N, Nb2C, Ta2C, Cr2C, Cr2N, Mo2C, Mo1.3C, Cr1.3C, (Ti, V)2C, (Ti, Nb)2C, W2C, W1.3C, Mo2N, Nb1.3C, Mo1.3Y0.6C (in the above formula, “1.3” and “0.6” mean about 1.3 (=4/3) and about 0.6 (=⅔), respectively.),
Typically, in the above formula, M may comprise Ti and X may be a carbon atom or a nitrogen atom, preferably M may be Ti and X may be a carbon atom. For example, the MAX phase is Ti3AlC2 and MXene is Ti3C2Ts (in other words, M is Ti, X is C, n is 2, and m is 3).
In the present disclosure, MXene may contain a relatively small amount of A atoms derived from the MAX phase of the precursor, for example, 10 mass % or less with respect to the original A atoms. The remaining amount of A atoms can be preferably 8% by mass or less, and more preferably 6% by mass or less. However, even if the residual amount of A atoms exceeds 10 mass %, there may be no problem depending on the application and use conditions of the two-dimensional particles.
The two-dimensional particles are an aggregate containing MXene particles (hereinafter, simply referred to as “MXene particles”)10a (single-layer MXene particles) of one layer schematically exemplified in
The two-dimensional particle may include one or plural layers. Examples of the MXene particles (multilayer MXene particles) of the plurality of layers include, but are not limited to, the MXene particle 10b of two layers as schematically shown in
Although the present embodiment is not limited, the thickness of each layer contained in the MXene particles (which corresponds to the MXene layers 7a, 7b) can be, for example, not less than 0.8 nm and not more than 5 nm, particularly not less than 0.8 nm and not more than 3 nm (it may vary mainly depending on the number of M atomic layers included in each layer). For individual layered bodies of multilayer MXene particles that may be included, the interlayer distance (Alternatively, the void dimension is indicated by Δd in
In one aspect, the ratio of (the average value of the major diameter of the two-dimensional surfaces of the two-dimensional particles)/(the average value of the thicknesses of the two-dimensional particles) is 1.2 or more, preferably 1.5 or more, and more preferably 2 or more. The average value of the major diameters of the two-dimensional surfaces of the two-dimensional particles and the average value of the thicknesses of the two-dimensional particles may be obtained by a method described later.
In one aspect, in the two-dimensional particles of the present embodiment the multilayer MXene particle that can be contained comprises a two-dimensional particles having a small number of layers obtained through a delamination treatment. The “small number of layers” means that, for example, the number of laminated MXene layers is six or less. In addition, the thickness of the multilayer MXene particle having a small number of layers in the lamination direction is preferably 15 nm or less, and more preferably 10 nm or less. Hereinafter, the “multilayer MXene particles having a small number of layers” may be referred to as “few-layer MXene particles”. The single-layer MXene particles and the few-layer MXene particles may be collectively referred to as “single-layer/few-layer MXene particles”. By containing the single-layer/few-layer MXene particles, the conductivity of the resulting membrane may increase.
In the multilayer MXene particle having a small number of layers, the ratio of (the average value of the major diameters of the two-dimensional surfaces of the two-dimensional particles)/(the average value of the thicknesses of the two-dimensional particles) is 1.2 or more, preferably not less than 1.5 and not more than 10, and more preferably not less than 2 and not more than 5. Hereinafter, the “MXene particles having a small number of layers” may be referred to as “few-layer MXene particles”. The single-layer MXene particles and the few-layer MXene particles may be collectively referred to as “single-layer/few-layer MXene particles”. As a result, the membrane formability of the membrane containing the two-dimensional particles can be improved.
Examples of the single-layer/few-layer MXene particles include two-dimensional particles obtained through delamination treatment.
In one aspect, the two-dimensional particles of the present embodiment preferably contains single-layer MXene particles and few-layer MXene particles, that is, single-layer/few-layer MXene particles. In the two-dimensional particles of the present embodiment, the proportion of the single-layer/few-layer MXene particles having a thickness of 15 nm or less is preferably 90 vol % or more, more preferably 95 vol % or more. As a result, the membrane formability of the membrane containing the two-dimensional particles can be improved.
In the two-dimensional particles of the present embodiment, the average value of the major diameters of the two-dimensional surfaces is not less than 0.01 μm and not more than 20 km. Hereinafter, the average value of the major diameters of the two-dimensional surfaces may be referred to as “average flake size”.
The larger the average flake size, the better the orientation of the two-dimensional particles in the material containing the two-dimensional particles. The orientation of the two-dimensional particles can be evaluated by, for example, the conductivity of the material containing the two-dimensional particles.
The average value of the major diameters of the two-dimensional surfaces is preferably 0.02 μm or more, and more preferably 0.05 μm or more. When the delamination treatment of MXene is performed by subjecting MXene to the ultrasonic treatment, most of MXene is reduced in diameter to about several hundred nanometers in terms of major diameter by the ultrasonic treatment, so that the membrane formed of the single-layer MXene delaminated by the ultrasonic treatment is considered to have low orientation of two-dimensional particles.
The average value of the major diameters of the two-dimensional surfaces is 20 km or less, preferably 15 μm or less, and more preferably 10 μm or less from the viewpoint of dispersibility in the dispersion medium.
The major diameter of the two-dimensional surface refers to a major diameter when each MXene particle is approximated to an elliptical shape in an electron microscope micrograph, and the average value of the major diameters of the two-dimensional surfaces refers to a number average of the major diameter of 80 particles or more. As the electron microscope, a scanning electron microscope (SEM) photograph or a transmission electron microscope (TEM) photograph can be used.
The average value of the major diameters of the two-dimensional particles of the present embodiment may be measured by dissolving a material containing the two-dimensional particles in a solvent and dispersing the two-dimensional particles in the solvent. Alternatively, it may be measured from an SEM image of the material.
The average value of the thicknesses of the two-dimensional particles of the present embodiment is preferably not less than 1 nm and not more than 15 nm. The thickness is preferably 10 nm or less, more preferably 7 nm or less, and still more preferably 5 nm or less. On the other hand, considering the thickness of the single-layer MXene particles, the lower limit of the thickness of the two-dimensional particles can be 1 nm.
The average value of the thicknesses of the two-dimensional particles is determined as a number average dimension (for example, a number average of at least 40) based on an atomic force microscope (AFM) photograph or a transmission electron microscope (TEM) photograph.
Hereinafter, a method for producing the two-dimensional particles is described in detail, but the present disclosure is not limited to such an embodiment.
The method for producing a two-dimensional particles comprises:
The method may further comprise:
In one aspect, the etched product and the delaminated product can be used as the two-dimensional particles, and preferably the etched and cleaned product can be used as the two-dimensional particles.
Hereinafter, each step is described in detail.
First, a predetermined precursor is prepared. The predetermined precursor that can be used in the present embodiment is a MAX phase that is a precursor of MXene, and represented by the following formula:
MmAXn
wherein M is at least one metal of Group 3, 4, 5, 6, or 7, and includes at least Ti, X is a carbon atom, a nitrogen atom, or a combination thereof, A is at least one group 12, 13, 14, 15, or 16 element, n is not less than 1 and not more than 4, m is more than n and not more than 5.
The above M, X, n, and m are as described above.
A is at least one Group 12, 13, 14, 15, or 16 element, is usually a Group A element, typically Group IIIA and Group IVA, and more particularly may contain at least one selected from the group consisting of Al, Ga, In, Tl, Si, Ge, Sn, Pb, P, As, S, and Cd, and is preferably Al.
The MAX phase has a crystal structure in which a layer constituted by A atoms is located between two layers represented by MmXn (each X may have a crystal lattice located in an octahedral array of M). When typically m=n+1, but not limited thereto, the MAX phase includes repeating units in which each one layer of X atoms is disposed in between adjacent layers of n+1 layers of M atoms (these are also collectively referred to as an “MmXn layer”), and a layer of A atoms (“A atom layer”) is disposed as a layer next to the (n+1)th layer of M atoms. The A atom layer (and optionally a part of the M atoms) is removed by selectively etching (removing and optionally layer-separating) the A atoms (and optionally a part of the M atoms) from the MAX phase.
The MAX phase can be produced by a known method. For example, a TiC powder, a Ti powder, and an Al powder are mixed in a ball mill, and the resulting mixed powder is fired under an Ar atmosphere to obtain a fired body (block-shaped MAX phase). Thereafter, the fired body obtained is crushed by an end mill to obtain a powdery MAX phase for the next step.
In a step (b), an etching treatment for removing at least a part of the A atoms from MmAXn of the precursor by etching is performed using an etching liquid. As a result, a treated product in which at least a part of the layer composed of A atoms is removed is obtained while maintaining the layer represented by MmXn in the precursor.
The etching liquid may contain an acid such as HF, HCl, HBr, HI, sulfuric acid, phosphoric acid, or nitric acid, and typically, an etching liquid containing an F atom can be used. Examples of the etching liquid include a mixed liquid of LiF and hydrochloric acid; a mixed liquid of hydrofluoric acid and hydrochloric acid; and a mixed liquid containing hydrofluoric acid, and these mixed liquids may further contain phosphoric acid or the like. The etching liquid can be typically an aqueous solution.
As the etching operation using the etching liquid and other conditions, conventionally performed conditions can be adopted.
In a step (c), the treated product obtained by the etching treatment is cleaned to obtain an etched and cleaned product. By performing the cleaning, the acid and the like used in the etching treatment can be sufficiently removed.
The cleaning can be performed using a cleaning liquid, and typically, can be performed by mixing an etched product and a cleaning liquid. Such a cleaning liquid typically contains water, and pure water is preferable. On the other hand, a small amount of hydrochloric acid or the like may be further contained in addition to pure water. The amount of the cleaning liquid to be mixed with the etched product and the method for mixing the etched product and the cleaning liquid are not particularly limited. For example, as such a mixing method, stirring, centrifugation, and the like are performed in a state where the etched product and the cleaning liquid coexist. Examples of the stirring method include a stirring method using a handshake, an automatic shaker, a share mixer, a pot mill, or the like. The degree of stirring such as the stirring speed and the stirring time may be adjusted according to the amount, concentration, and the like of the etched product target to be treated. The cleaning with the cleaning liquid may be performed once or more, and it is preferable to perform the cleaning in the cleaning plural times. For example, specifically, the cleaning with a cleaning liquid may be performed by sequentially performing step (i) (to the treated product or the remaining precipitate obtained in the following (iii)), adding the cleaning liquid and stirring, step (ii) centrifuging the stirred product, and step (iii) discarding the supernatant liquid after centrifugation, and the steps (i) to (iii) may be repeated within a range of two times or more, for example, 15 times or less.
In a step (d), an intercalation treatment of intercalating a metal cation is performed on the etched and cleaned product using a metal compound containing a metal cation to obtain an intercalated product. As a result, an intercalated product in which the metal cation is intercalated between two adjacent MmXn layers is obtained. Such an intercalation treatment may be performed in a dispersion medium.
The metal cation may be the same as the metal cation contained in the two-dimensional particles, and may contain a Li cation or another metal cation.
However, the metal of the metal cation is different from the M atom. In addition, the metal of the metal cation is different from the A atom contained in the precursor.
Examples of the metal compound include an ionic compound in which the metal cation and the anion are bonded. Examples of the metal compound include a salt of the metal cation including an iodide, a phosphate, sulfide salt including a sulfate, a nitrate, an acetate, and a carboxylate. As the metal cation, a lithium ion is preferable, and as the metal compound, a metal compound containing a lithium ion is preferable, an ionic compound of a lithium ion is more preferable, and one or more of an iodide, a phosphate, and a sulfide salt of a lithium ion is further preferable. When a lithium ion is used as the metal ion, it is considered that water hydrated to the lithium ion has the most negative dielectric constant, and thus it is easy to form a single-layer.
A specific method of the intercalation treatment is not particularly limited, and for example, the etched and cleaned product and the metal compound may be mixed and stirred, or may be left to stand. The examples include stirring at room temperature. Examples of the stirring method include a method using a stirring bar such as a stirrer, a method using a stirring blade, a method using a mixer, a method using a centrifugal device, and the like, and the stirring time can be set according to the production scale of the single-layer/few-layer MXene particles, and can be set, for example, for 12 to 24 hours.
The intercalation treatment may be performed in the presence of a dispersion medium. Examples of the dispersion medium include water; and organic media such as N-methylpyrrolidone, N-methylformamide, N,N-dimethylformamide, methanol, ethanol, dimethylsulfoxide, ethylene glycol, and acetic acid.
The order of mixing the dispersion medium, the etched and cleaned product, and the metal compound is not particularly limited, but In one aspect, the metal compound may be mixed after mixing the dispersion medium and the etched and cleaned product. Typically, the etching liquid after the etching treatment may be used as the dispersion medium.
The intercalation treatment can be typically performed on the etched and cleaned product, but in another aspect, the precursor may be performed simultaneously with the etching treatment. Specifically, such an etching and intercalation treatment includes mixing a precursor, an etching liquid, and a metal compound containing a metal cation to remove at least some A atoms from the precursor, and intercalating the metal cation with the precursor from which the A atoms have been removed to obtain an intercalated product. As a result, at least a part of the A atoms is removed from the precursor (MAX), the MmXn layer in the precursor remains, and an intercalated product in which the metal cation is intercalated between the plurality of adjacent MmXn layers is obtained.
As the etching liquid and the metal compound used in the etching and intercalation treatment, the same etching liquid and metal compound as those used in the step (b) can be used, respectively.
In a step (e), the intercalated product is stirred, and a delamination treatment for delaminating the intercalated product is performed to obtain a delaminated product. By such stirring, a shear stress is applied to the intercalated product, and at least a part between two adjacent MmXn layers can be peeled off, and the MXene particles may become single-layered and few-layered.
Conditions for the delamination treatment are not particularly limited, and the delamination treatment can be performed by a known method. The example of the method of applying a shear stress to the intercalated product include dispersing the intercalated product in a dispersion medium and stirring the dispersion medium. Examples of the stirring method include stirring using a mechanical shaker, a vortex mixer, a homogenizer, ultrasonic treatment, a handshake, an automatic shaker, or the like. The degree of stirring such as the stirring speed and the stirring time may be adjusted according to the amount, concentration, and the like of the product target to be treated. For example, the slurry after the intercalation is centrifuged to discard the supernatant liquid, then pure water is added to the remaining precipitate, and stirring is performed by, for example, a handshake or an automatic shaker to perform layer separation. The removal of the unpeeled substance includes a step of performing centrifugal separation to discard the supernatant, and then cleaning the remaining precipitate with water. For example, (i) pure water is added to the remaining precipitate after discarding the supernatant and stirred, (ii) centrifugation is performed, and (iii) the supernatant liquid is recovered. This operation of (i) to (iii) is repeated one time or more, preferably two times or more and 10 times or less to obtain a supernatant liquid containing single-layer/few-layer MXene particles as a delaminated product. Alternatively, the supernatant liquid may be centrifuged, and the supernatant liquid after centrifugation may be discarded to obtain a clay containing single-layer/few-layer MXene particles as a delaminated product.
The delaminated product may be further cleaned. By such cleaning, at least a part of impurities and the like can be removed. Hereinafter, a treated product obtained by cleaning the delaminated product is also referred to as a delaminated cleaned product, and the delaminated cleaned product is included in the technical scope of the delaminated product.
In one aspect, the cleaning can be performed using a cleaning liquid, and typically, the cleaning can be performed by mixing the delaminated product and the cleaning liquid. In another aspect, the cleaning can be performed by acid-treating the delaminated product and then mixing the acid-treated product with a cleaning liquid. Examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, hydroiodic acid, hydrobromic acid, and hydrofluoric acid; organic acids such as acetic acid, citric acid, oxalic acid, benzoic acid, or sorbic acid, and these may be appropriately used. The concentration of the acid in the acid solution can be appropriately adjusted according to the delaminated product. In addition, the cleaning with a cleaning liquid may be performed by sequentially performing step (i) (to the treated product or the remaining precipitate obtained in the following (iii)), adding the cleaning liquid and stirring, step (ii) centrifuging the stirred product, and step (iii) discarding the supernatant liquid after centrifugation, and the steps (i) to (iii) may be repeated within a range of two times or more, for example, 15 times or less. The stirring can be performed using a handshake, an automatic shaker, a share mixer, a pot mill, or the like. The acid treatment may be performed one or more times, and if necessary, an operation of mixing with a fresh acid solution (acid solution not used for the acid treatment) and stirring may be performed within a range of two or more times, for example, 10 times or less. As the cleaning liquid, the same cleaning liquid as the cleaning liquid in the step (c) can be used. For example, specifically, water may be used as the cleaning liquid, and pure water is preferable. The mixing can be performed by the same method as the mixing method in the step (c), and specific examples thereof include stirring and centrifugation. Examples of the stirring method include a stirring method using a handshake, an automatic shaker, a share mixer, a pot mill, or the like.
The intermediate and the target product in the production method described above, for example, the intercalated product and the delaminated product may be dried by suction filtration, heat drying, freeze drying, vacuum drying, or the like.
The proportion of the two-dimensional particles in the membrane of the present disclosure may be preferably not less than 20 vol % and not more than 100 vol %, more preferably not less than 50 vol % and not more than 100 vol %, still more preferably not less than 70 vol % and not more than 100 vol %, still more preferably not less than 90 vol % and not more than 100 vol %, and still more preferably not less than 95 vol % and not more than 100 vol %.
The adsorbent material of the present disclosure may further contain one or more materials selected from a ceramics, a metal, and a resin in addition to the two-dimensional particles. For example, when the adsorbent material in the present embodiment contains a material such as a ceramics, a metal, or a resin, the adsorption can be readily performed with stability.
Examples of the ceramics include metal oxides such as silica, alumina, zirconia, titania, magnesia, cerium oxide, zinc oxide, barium titanate-based, hexaferrite, and mullite, and non-oxide ceramics such as silicon nitride, titanium nitride, aluminum nitride, silicon carbide, titanium carbide, tungsten carbide, boron carbide, and titanium boride.
Examples of the metal include metals of Groups 2 to 13 such as iron, titanium, magnesium, and aluminum; and an alloy based on the Group 2 to Group 13 metals.
The resin may be either a natural resin or a synthetic resin, and examples thereof include a hydrophilic resin and a hydrophobic resin. Such a hydrophilic resin may include a hydrophilic resin obtained by blending a hydrophilic auxiliary agent such as a surfactant into a hydrophobic resin to exhibit hydrophilicity, and a hydrophobic resin partially modified with a hydrophilic group.
Examples of the hydrophilic resin include a resin having a polar group (for example, a hydroxyl group, a substituted or unsubstituted amino group, a carboxyl group, a sulfonic acid group, a carbonyl group, an ester bond, an amide bond, or the like), and specific examples thereof include cellulose-based resins such as cellulose, cellulose acetate, and regenerated cellulose; polysulfone-based resins such as polysulfone and polyethersulfone; hydrophilic polyurethane; polyvinyl alcohol and copolymer thereof, sodium alginate; an acrylic resin; substituted or unsubstituted polyacrylamide; acrylonitrile; polyaniline sulfonic acid; and a polyamide resin such as nylon.
In one aspect, the hydrophilic resin is preferably a resin having a group capable of forming a hydrogen bond with a modifier or terminal T of the layer as the polar group. Examples of such a group include a carboxyl group, a sulfonic acid group, a carbonyl group, and an amide bond. Examples of the resin having these groups include water-soluble polyurethane, polyvinyl alcohol, sodium alginate, an acrylic acid-based water-soluble polymer, polyacrylamide, polyaniline sulfonic acid, and nylon, and among them, water-soluble polyurethane, polyvinyl alcohol, and sodium alginate are preferable, and water-soluble polyurethane is more preferable.
In another aspect, as the hydrophilic resin, an acrylic resin; polyacrylonitrile; cellulose-based resin; polysulfone-based resin; polyvinyl alcohol and copolymers thereof are preferable, polymethyl methacrylate, polyacrylonitrile, cellulose, cellulose acetate, polysulfone, polyvinyl alcohol, and copolymers of polyvinyl alcohol and polyethylene are more preferable, polysulfone, polymethyl methacrylate, and cellulose acetate are still more preferable, and polysulfone and polymethyl methacrylate are still more preferable. These resins can be used for dialysis, hemofiltration, and the like, and are suitable when the adsorbent material of the present disclosure is applied to a dialysis machine.
Examples of the hydrophobic resin include a resin not containing the polar group.
The adsorbent material of the present disclosure can be produced using the two-dimensional particles. The two-dimensional particle may be used as it is as the adsorbent material of the present disclosure, or the two-dimensional particles and one or more materials selected from a ceramics, a metal, and a resin to be used as necessary may be mixed and molded into a predetermined shape to form the adsorbent material.
In one aspect, when the adsorbent material contains a resin, the adsorbent material can be produced by mixing the two-dimensional particles and the resin to form a mixture and molding the mixture.
The mixing of the two-dimensional particles and the resin may be performed in the absence of a solvent or in the presence of a dispersion medium. Such a dispersion medium is typically water, and in some cases, other liquid substances may be contained in a relatively small amount (For example, 30% by mass or less, preferably 20% by mass or less based on the whole mass) in addition to water.
The two-dimensional particles and the resin can be stirred using a dispersing device such as a homogenizer, a propeller stirrer, a thin membrane swirling stirrer, a planetary mixer, a mechanical shaker, or a vortex mixer.
The molding method is not particularly limited, and for example, the mixture of the two-dimensional particles and the resin may be molded as it is into a predetermined shape, and the two-dimensional particles, the resin, and the dispersion medium may be mixed to obtain a mixture, such a mixture may be applied to a base material (for example, a substrate) to obtain a precursor membrane containing the dispersion medium, and at least a part of the dispersion medium contained in the precursor membrane may be removed by drying such a precursor membrane to form a membrane. Examples of the application method include a method of performing spray applying using a nozzle such as a one-fluid nozzle, a two-fluid nozzle, or an air brush, a method such as slit coating using a table coater, a comma coater, or a bar coater, screen printing, or metal mask printing, and an application method by spin coating, immersion, or dropping.
The application and drying may be repeated a plurality of times as necessary until a membrane having a desired thickness is obtained. The drying may be performed at a temperature of 400° C. or less using, for example, a normal pressure oven or a vacuum oven.
In another aspect, when the adsorbent material contains a ceramics or a metal, the adsorbent material can be produced by mixing the two-dimensional particles with, for example, a particulate ceramics or a metal and heating the mixture at a low temperature at which the composition of the two-dimensional particles can be maintained.
The adsorbent material is used for adsorbing a disease-causing substance, and can be used, for example, for adsorbing and removing or reducing the disease-causing substance in blood. The fact that the adsorbent material can adsorb the disease-causing substance can be confirmed, for example, in an adsorption test using human plasma.
The disease-causing substance preferably includes a protein. Examples of such a protein include uremic proteins (specifically, a medium-molecular-type uremic substance) such as parathyroid hormone, β2-microglobulin, and tumor necrosis factor (TNF)-α; cytokines (in one aspect, an inflammatory cytokine such as interleukin 18) such as interleukins, interferons, chemokines, hematopoietic factors, cell growth factors, and tumor necrosis factors; and other proteins such as albumin and M protein. The uremic protein (specifically, a medium-molecular-type uremic substance) corresponds to a uremic substance, and is expected to have a preventive effect on uremia by adsorbing the uremic substance. The inflammatory cytokine can cause various inflammatory symptoms in vivo, and an effect of preventing inflammation is expected by adsorbing them.
In the present disclosure, “uremic” means that the concentration in blood increases as the function of the kidney decreases, and can cause various symptoms associated with a renal disease such as an acute kidney disorder (including acute renal failure) and a chronic kidney disease (chronic renal failure, including end-stage renal failure), particularly various symptoms associated with a renal disorder.
In addition, by adsorbing an inflammatory substance as a disease-causing substance, the effect of preventing various symptoms associated with an inflammatory disease is expected. Various symptoms associated with an inflammatory disease include vascular dementia, inflammatory bowel disease, hepatitis, and myocarditis.
The disease-causing substance preferably contains an electrolyte (ionic substance). That is, the adsorbent material can also be used for adsorbing an electrolyte. Examples of such an electrolyte include a cation and an anion. Examples of such a cation include cations that can be excreted in the kidneys, and specifically include Na+, K+, Mg2+, and Ca2+. In the present disclosure, the anion includes an anion that can be excreted in the kidney, and specifically includes an anion containing P (for example, PO43−).
When the renal function decreases, the concentration of the electrolyte (in particular, an electrolyte which can be excreted in the kidney.) in the blood may increase, which may cause electrolyte imbalance such as hypernatremia, hyperkalemia, hypomagnesemia, and hyperphosphatemia. By adsorbing these electrolytes by the amount of the adsorbent material, the effect of preventing electrolyte imbalance is expected.
The disease-causing substance preferably further includes a protein-bound uremic substance such as creatinine, homocysteine, indoxyl sulfate, or p-cresyl sulfate; and a carcinogen. That is, the adsorbent can also be used for adsorbing a protein-bound uremic substance and a carcinogen. Therefore, by using the adsorbent material containing the two-dimensional particles as a separation membrane in a dialysis machine, the effect of treating and preventing the various diseases is expected.
The adsorbate of the present disclosure is expected to prevent or treat various symptoms associated with a renal disease such as an acute kidney disorder (including acute renal failure) and a chronic kidney disease (chronic renal failure, including end-stage renal failure), various symptoms associated with an inflammatory disease, particularly various symptoms associated with a renal disorder and/or an inflammatory disease, by being capable of adsorbing the adsorbent material. Specifically, It is expected to prevent or treat inflammatory diseases such as uremia; electrolyte imbalance such as hypernatremia, hyperkalemia, hypermagnesemia and hyperphosphatemia; autoimmune diseases; infectious diseases; inflammatory diseases; endocrine and metabolic diseases; circulatory disorders; blood diseases; gastrointestinal diseases; neuropathy; malignant tumors; drug intoxication; vascular dementia, inflammatory bowel disease, hepatitis, and myocarditis.
An adsorption method including adsorbing the disease-causing substance using the adsorbent material is also included in the technical scope of the present disclosure. Such an adsorption method preferably includes adsorbing a protein as a disease-causing substance using the adsorbent material. The adsorption method may further include adsorbing an electrolyte as a disease-causing substance. That is, the adsorption method may include adsorbing the protein and the electrolyte as the disease-causing substance using the adsorbent material. Such an adsorption method may further include adsorbing another adsorbate using the adsorbent material. In one aspect, the adsorption of the disease-causing substance can be performed by contacting the liquid containing an adsorbate such as a protein or an electrolyte as the disease-causing substance with the adsorbent material. The liquid containing such an adsorbate may contain substances other than the protein and the electrolyte as the disease-causing substances. Specific examples of the liquid containing the adsorbate include blood and a dialysate.
The adsorbent sheet in the present embodiment includes the adsorbent material. By containing the adsorbent material, such an adsorbent sheet can adsorb various adsorbates, particularly the disease-causing substance, and the adsorbent material can be physically fixed, so that adsorption performance can be stably exhibited.
The adsorbent sheet in the present embodiment may be made of the adsorbent material, and may further contain one or more materials selected from the ceramics, the metal, and the resin in addition to the adsorbent material. As the ceramics, the metal, and the resin, the same materials as the ceramic, the metal, and the resin that can be contained in the adsorbent material can be used, respectively.
When the adsorbent sheet in the present embodiment further contains one or more materials selected from the ceramics, the metal, and the resin, the adsorbent sheet may include a member in which the adsorbent material and the material are uniformly mixed, or may include a member containing the adsorbent material and a member containing the material, respectively.
In one aspect, the adsorbent sheet in the present embodiment includes a base material containing one selected from the above ceramics, a metal, and a resin; and a membrane containing the adsorbent material and disposed on the base material. The membrane containing such an adsorbent material may cover at least a part of the surface of the base material and may cover the entire surface of the base material.
The adsorbent sheet can be produced by forming a membrane containing an adsorbent material on a surface of the base material. The method for producing a membrane containing the adsorbent material is not particularly limited, and may include, for example, mixing the two-dimensional particles, a dispersion medium, and if necessary, two-dimensional particles to obtain a mixture, applying the mixture onto the base material to obtain a precursor membrane containing a dispersion medium, and drying the precursor membrane to remove at least a part of the dispersion medium contained in the precursor membrane to form a membrane. As a method of applying the mixture to the base material, for example, commonly used application methods such as immersion, brush, roller, roll coater, air spray, airless spray, curtain flow coater, roller curtain coater, die coater, and electrostatic coating can be used. The thickness of the adsorbent sheet and the thickness of the substrate can be appropriately set according to the application.
The separation membrane in the present embodiment contains the adsorbent material. By containing the adsorbent material, such a separation membrane can adsorb various adsorbates, particularly the disease-causing substance, and the adsorbent material can be physically fixed, so that adsorption performance can be stably exhibited. The separation membrane in the present embodiment is particularly suitable for a separation membrane for artificial dialysis used for the hemodialysis or the like.
The separation membrane may be made of the adsorbent material, and may further contain one or more materials selected from the ceramics, the metal, and the resin in addition to the adsorbent material. In one aspect, it may include a base material and a base material containing one selected from the ceramics, the metal, and the resin; and a membrane containing the adsorbent material and disposed on the base material. The membrane containing such an adsorbent material may cover at least a part of the surface of the base material and may cover the entire surface of the base material. The shape of the base material is not particularly limited, and may be a film shape, a sheet shape, a plate shape, a porous shape, a hollow fiber shape, a bead shape, or the like.
As the ceramics, the metal, and the resin, the same materials as the ceramic, the metal, and the resin that can be contained in the adsorbent material can be used, respectively. Among them, cellulose-based and synthetic polymer-based materials used for hemodialysis and the like are preferable, and specifically, polymethyl methacrylate, polyacrylonitrile, cellulose, cellulose acetate, polysulfone, polyvinyl alcohol, vinyl alcohol copolymers such as copolymers of polyvinyl alcohol and ethylene, and the like can be preferably used, polysulfone, polymethyl methacrylate, and cellulose acetate are more preferably used, and polysulfone and polymethyl methacrylate are still more preferably used. The form of the separation membrane for artificial dialysis is not particularly limited, and examples thereof include a porous type, a hollow fiber type, and a flat membrane layered type.
The artificial dialysis machine according to the present embodiment includes the adsorbent material. By containing the adsorbent material, such an artificial dialysis machine can adsorb various adsorbates, particularly a disease-causing substance, and can be used for adsorption and removal of various waste products in hemodialysis, hemofiltration, hemodiafiltration, peritoneal dialysis, and the like. In other words, the adsorbent material of the present embodiment can be used in an artificial dialysis machine for performing the hemodialysis, hemofiltration, hemodiafiltration, peritoneal dialysis, and the like.
The artificial dialysis machine is classified into, for example, a hemodialysis machine and a peritoneal dialysis machine, and the hemodialysis machine is divided into a one-pass type (single-pass type) and a circulation type. Further, the circulation type includes by REDY systems (recirculating dialysate systems) and other systems. The artificial dialysis machine is also classified according to a method of removing urea without coming into contact with blood by a cross flow of blood and a dialysate from a patient and a method of directly filtering blood. In addition, a one-pass type peritoneal dialysis machine is mainly used. The adsorbent material of the present embodiment can be used for both of the hemodialysis and the peritoneal dialysis, and can be used as an adsorption membrane, a separation membrane, an adsorbent material cartridge, or the like in an artificial dialysis machine such as a hemodialysis machine or a peritoneal dialysis machine. For example, when used in a REDY system (recirculating dialysate system), the adsorbent material of the present embodiment may be used in the adsorbent material cartridge.
In the hemodialysis machine 40A of
The separation membrane 45A may be cladded with a resin or the like and disposed in the form of a column. In the column, a filter may be disposed on each of the blood inflow side and the blood outflow side of the column so that blood is distributed in the separation membrane 45A.
In the hemodialysis machine 40A of
The present disclosure is described more specifically with reference to the following Examples, but the present disclosure is not limited thereto.
In Examples 1 and 2, (1) preparation of the precursor (MAX), (2) etching of the precursor, and (3) cleaning and drying described in detail below were sequentially performed to prepare two-dimensional particles.
TiC powder, Ti powder, and Al powder (all manufactured by Kojundo Chemical Laboratory Co., Ltd.) were placed in a ball mill containing zirconia balls at a molar ratio of 2:1:1 and mixed for 24 hours. The resulting mixed powder was fired at 1,350° C. for 2 hours under an Ar atmosphere. The fired body (block) thus obtained was crushed with an end mill to a maximum size of 40 μm or less. In this way, Ti3AlC2 particles were obtained as a precursor (MAX).
Using the Ti3AlC2 particles (powder) prepared by the above method, etching was performed under the following etching conditions to obtain a solid-liquid mixture (slurry) containing a solid component derived from the Ti3AlC2 powder.
The slurry was divided into two portions, each of which was inserted into two 50 mL centrifuge tubes, centrifuged under the condition of 3,500 G using a centrifuge, and then the supernatant liquid was discarded. An operation of adding 40 mL of pure water to each centrifuge tube, centrifuging again at 3,500 G, and separating and removing the supernatant liquid was repeated 11 times. After final centrifugation, the supernatant liquid was discarded to obtain a Ti3C2Ts-water medium clay. The obtained clay was dried by freeze drying to obtain a dried powder of two-dimensional particles.
In Example 2, (1) the precursor (MAX) was prepared in the same manner as in Example 1, then the following step (2) was performed, and (3) cleaning and drying were performed in the same manner as in Example 1 to prepare two-dimensional particles.
In Example 3, (1) the precursor (MAX) was prepared in the same manner as in Example 1, then the following step (2) was performed, and (3) cleaning and drying were performed in the same manner as in Example 1 to prepare two-dimensional particles.
In Example 4, (1) the precursor (MAX) was prepared in the same manner as in Example 1, then the following step (2) was performed, and (3) cleaning and drying were performed in the same manner as in Example 1 to prepare two-dimensional particles.
In Example 5, (1) preparation of the precursor (MAX), (2) etching of the precursor, and (3) cleaning and drying described in detail below were sequentially performed to prepare two-dimensional particles.
Into a ball mill containing a zirconia ball, 73 g of Ti powder, 47.2 g of TiN powder, 20.6 g of Al powder, and 9.2 g of C powder (all manufactured by Kojundo Chemical Laboratory Co., Ltd.) were charged, and mixed for 24 hours. The resulting mixed powder was fired at 1,400° C. for 2 hours under an Ar atmosphere. The fired body (block) thus obtained was crushed with an end mill to a maximum size of 40 μm or less. In this way, Ti3AlCN particles were obtained as a precursor (MAX).
Using the Ti3AlCN particles (powder) prepared by the above method, etching was performed under the following etching conditions to obtain a solid-liquid mixture (slurry) containing a solid component derived from the Ti3AlCN powder.
The slurry was divided into two portions, each of which was inserted into two 50 mL centrifuge tubes, centrifuged under the condition of 3,500 G using a centrifuge, and then the supernatant liquid was discarded. An operation of adding 40 mL of pure water to each centrifuge tube, centrifuging again at 3,500 G, and separating and removing the supernatant liquid was repeated 11 times. After final centrifugation, the supernatant liquid was discarded to obtain a Ti3CNTs-water medium clay. The obtained clay was dried by freeze drying to obtain a dried powder of two-dimensional particles.
In Example 6, (1) preparation of the precursor (MAX), (2) etching of the precursor, and (3) cleaning and drying described in detail below were sequentially performed to prepare two-dimensional particles.
Into a ball mill containing zirconia balls, 21.5 g of the V powder, 6.3 g of the Al powder, and 2.3 g of the C powder (all manufactured by Kojundo Chemical Laboratory Co., Ltd.) were charged, and mixed for 24 hours. The resulting mixed powder was fired at 1,550° C. for 2 hours under an Ar atmosphere. The fired body (block) thus obtained was crushed with a jaw crusher to a maximum dimension of 45 μm or less. In this way, V2AlC particles were obtained as a precursor (MAX).
Using the V2AlC particles (powder) prepared by the above method, etching was performed under the following etching conditions to obtain a solid-liquid mixture (slurry) containing a solid component derived from the V2AlC powder.
The slurry was divided into two portions, each of which was inserted into two 50 mL centrifuge tubes, centrifuged under the condition of 3,500 G using a centrifuge, and then the supernatant liquid was discarded. An operation of adding 40 mL of pure water to each centrifuge tube, centrifuging again at 3,500 G, and separating and removing the supernatant liquid was repeated 11 times. After final centrifugation, the supernatant liquid was discarded to obtain a V2CTs-water medium clay. The obtained clay was dried by freeze drying to obtain a dried powder of two-dimensional particles.
In Example 7, (1) preparation of the precursor (MAX), (2) etching of the precursor, and (3) cleaning and drying described in detail below were sequentially performed to prepare two-dimensional particles.
In a ball mill containing zirconia balls, 105.4 g of Ti powder, 32.7 g of Al powder, and 11.9 g of C powder (all manufactured by Kojundo Chemical Laboratory Co., Ltd.) were charged, and mixed for 24 hours. The resulting mixed powder was fired at 1,550° C. for 2 hours under an Ar atmosphere. The fired body (block) thus obtained was crushed with an end mill to a maximum size of 40 μm or less. In this way, Ti2AlC particles were obtained as a precursor (MAX).
Using the Ti2AlC particles (powder) prepared by the above method, etching was performed under the following etching conditions to obtain a solid-liquid mixture (slurry) containing a solid component derived from the Ti2AlC powder.
The slurry was divided into two portions, each of which was inserted into two 50 mL centrifuge tubes, centrifuged under the condition of 3,500 G using a centrifuge, and then the supernatant liquid was discarded. An operation of adding 40 mL of pure water to each centrifuge tube, centrifuging again at 3,500 G, and separating and removing the supernatant liquid was repeated 11 times. After final centrifugation, the supernatant liquid was discarded to obtain a Ti2CTs-water medium clay. The obtained clay was dried by freeze drying to obtain a dried powder of two-dimensional particles.
In Example 8, (1) preparation of the precursor (MAX), (2) etching of the precursor, and (3) cleaning and drying described in detail below were sequentially performed to prepare two-dimensional particles.
TiC powder, Ti powder, and Al powder (all manufactured by Kojundo Chemical Laboratory Co., Ltd.) were placed in a ball mill containing zirconia balls at a molar ratio of 2:1:1 and mixed for 24 hours. The obtained mixed powder was calcined in an Ar atmosphere at 1350° C. for 2 hours. The fired body (block) thus obtained was crushed with an end mill to a maximum size of 40 μm or less. As a result, Ti3AlC2 particles were obtained as MAX particles.
Using the Ti3AlC2 particles (powder) prepared by the above method, etching was performed under the following etching conditions to obtain a solid-liquid mixture (slurry) containing a solid component derived from the Ti3AlC2 powder.
The slurry was divided into two portions, each of which was inserted into two 50 mL centrifuge tubes, centrifuged under the condition of 3500 G using a centrifuge, and then the supernatant liquid was discarded. An operation of adding 40 mL of pure water to the remaining precipitate in each centrifuge tube, centrifuging again at 3500 G, and separating and removing the supernatant liquid was repeated 11 times. After final centrifugation, the supernatant liquid was discarded to obtain a Ti3C2Tx-water medium clay. The obtained clay was dried by freeze drying to obtain a dried powder of two-dimensional particles.
In Example 9, (1) preparation of the precursor (MAX), (2) etching of the precursor, and (3) cleaning and drying described in detail below were sequentially performed to prepare two-dimensional particles.
TiC powder, Ti powder, and Al powder (all manufactured by Kojundo Chemical Laboratory Co., Ltd.) were placed in a ball mill containing zirconia balls at a molar ratio of 2:1:1 and mixed for 24 hours. The obtained mixed powder was calcined in an Ar atmosphere at 1350° C. for 2 hours. The fired body (block) thus obtained was crushed with an end mill to a maximum size of 40 μm or less. As a result, Ti3AlC2 particles were obtained as MAX particles.
Using the Ti3AlC2 particles (powder) prepared by the above method, etching was performed under the following etching conditions to obtain a solid-liquid mixture (slurry) containing a solid component derived from the Ti3AlC2 powder.
The slurry was divided into two portions, each of which was inserted into two 50 mL centrifuge tubes, centrifuged under the condition of 3500 G using a centrifuge, and then the supernatant liquid was discarded. An operation of adding 40 mL of pure water to the remaining precipitate in each centrifuge tube, centrifuging again at 3500 G, and separating and removing the supernatant liquid was repeated 11 times. After final centrifugation, the supernatant liquid was discarded to obtain a Ti3C2Tx-water medium clay. The obtained clay was dried by freeze drying to obtain a dried powder of two-dimensional particles.
In Example 10, (1) preparation of a precursor (MAX), (2) etching of the precursor, (3) cleaning, (4) Li intercalation, (5) delamination, (6) modification with an amino group, and drying described in detail below were sequentially performed to prepare two-dimensional particles.
TiC powder, Ti powder, and Al powder (all manufactured by Kojundo Chemical Laboratory Co., Ltd.) were placed in a ball mill containing zirconia balls at a molar ratio of 2:1:1 and mixed for 24 hours. The obtained mixed powder was calcined in an Ar atmosphere at 1350° C. for 2 hours. The fired body (block) thus obtained was crushed with an end mill to a maximum size of 40 μm or less. As a result, Ti3AlC2 particles were obtained as MAX particles.
Using the Ti3AlC2 particles (powder) prepared by the above method, etching was performed under the following etching conditions to obtain a solid-liquid mixture (slurry) containing a solid component derived from the Ti3AlC2 powder.
The slurry was divided into two portions, each of which was inserted into two 50 mL centrifuge tubes, centrifuged under the condition of 3500 G using a centrifuge, and then the supernatant liquid was discarded. An operation of adding 40 mL of pure water to the remaining precipitate in each centrifuge tube, centrifuging again at 3500 G, and separating and removing the supernatant liquid was repeated 11 times. After final centrifugation, the supernatant liquid was discarded to obtain a Ti3C2Tx-water medium clay.
The Ti3C2Tx-water medium clay prepared by the above method was stirred at not less than 20° C. and not more than 25° C. for 12 hours using LiCl as a Li-containing compound to perform Li intercalation according to the following conditions.
(i) To the Ti3C2Tx-water medium clay, 40 mL of pure water was added, then the mixture was stirred with a shaker for 15 minutes, (ii) the mixture was centrifuged at 3500 G, and (iii) the supernatant liquid was recovered as a single-layer MXene-containing liquid. The operations (i) to (iii) were repeated four times in total to obtain a single-layer MXene-containing supernatant liquid. Further, this supernatant liquid was centrifuged under the conditions of 4,300 G and 2 hours using a centrifuge, and then the supernatant liquid was discarded to obtain a single-layer/few-layer MXene-containing clay as a single-layer/few-layer MXene-containing sample.
(6) Modification with Amino Group and Drying
To 0.34 g of single-layer/few-layer MXene-containing clay, 20 mg of 6-aminohexyl phosphate hydrochloride and 5 mL of pure water were added, and the mixture was stirred at room temperature at a stirrer rotation speed of 800 rpm for 2 hours. The obtained slurry was centrifuged at a rotation speed of 8,000 rpm for 8 minutes, and the supernatant liquid was discarded. Pure water having the same volume as the discarded supernatant liquid was added, and centrifuged at a rotation speed of 8,000 rpm for 8 minutes. Discard of the supernatant liquid, addition of pure water having the same volume as that of the discarded supernatant liquid, and centrifugation at a rotation speed of 8,000 rpm for 8 minutes were repeated once. Subsequently, the supernatant liquid was discarded, and ethanol having the same volume as that of the discarded supernatant liquid was added and dispersed, and then naturally dried to obtain Ti3C2 particles (powder) modified with an amino group.
The spherical adsorption charcoal (“KREMEZIN Tablets 500 mg”, manufactured by KUREHA CORPORATION) was powdered using a mortar and subjected to adsorption evaluation.
An adsorption type blood purifier (“Lixelle”, manufactured by KANEKA CORPORATION) was disassembled, and the extracted adsorbing body was subjected to adsorption evaluation.
A medicinal charcoal (manufactured by Nichi-Iko Pharmaceutical Co., Ltd.) was subjected to adsorption evaluation.
Human plasma collected from a healthy subject, two-dimensional particles of Example, and spherical adsorption charcoal, adsorption type blood purifier, or medicinal charcoal of Comparative Example (hereinafter, these are collectively referred to as “adsorbent material”) were weighed in a 50 mL centrifuge tube, and shaken and stirred for 60 minutes using a constant temperature shaker (TAITEC BR-33FL) set at 37° C. Thereafter, several mL of the mixed solution was sampled, the adsorbent material was separated with a syringe filter (Millex diameter for Merck Millipore sterilization: 33 mm, hole diameter: 0.45 μm) having a hole diameter of 0.45 μm, and then component analysis was performed. In Examples 1 to 4 and Comparative Example 1 to 3, the human plasma amount was 10 mL and the adsorbent material amount was 0.6 g, in Example 5 to 8 and Example 10, the human plasma amount was 4 mL and the adsorbent material amount was 0.2 g, and in Example 9, the human plasma amount was 4 mL and the adsorbent material amount was 0.2 g.
In Examples 1 to 4 and Comparative Examples 1 to 3, component analysis was performed for Na, P, K, Urea, Creatinine, Homocysteine, Folic acid, Parathyroid hormone (Prathyroid hormone), β2-microglobulin (β2-microgloblin), Interleukin-18, Trypsin, TNF-α (Tumor necrosis factor-α), α-amylase, and Albumin.
In Examples 5 to 10, component analysis was performed for Albumin, Chlor (Cl), serum urea nitrogen (BUN), α-amylase (AMY), lipase, Na, K, inorganic phosphorus (IP), and β2-microglobulin.
The measurement of Na, K and Cl was performed by an electrode method; the measurement of P, inorganic phosphorus, α-amylase, lipase, and creatinine was performed by an enzymatic method; the measurement of urea and serum urea nitrogen was performed by a urease/GLDH/UV method; the measurement of homocysteine was performed by HPLC method; the measurement of folic acid was performed by the CLIA method; the measurement of parathyroid hormone was performed by the ECLIA method; the measurement of β2-microglobulin was performed by a latex agglutination method; the measurement of interleukin-18, trypsin, and TNF-α was performed by an EIA method; the measurement of albumin was performed by a colorimetric method (BGC method).
Note that the same treatment was also performed on the sample containing no adsorbent material and containing only human plasma in the centrifuge tube, and the sample was used as a baseline of component concentration. The concentration of the component A contained in the human plasma after the adsorption test was performed was defined as CA1, and the concentration of the component A at the baseline was defined as CA0, and the adsorption removal rate was calculated based on the following formula. When the adsorption removal rate was less than 0% by mass, the adsorption removal rate was set to 0% by mass.
The results are shown in Tables 1 and 2.
It was confirmed that the adsorbent materials of Examples 1 to 4 adsorb, as disease-causing substances, middle molecular type uremic substances such as parathyroid hormone, β2-microglobulin, and tumor necrosis factor (TNF)-α; inflammatory cytokines such as interleukin-18; and proteins such as albumin, and further exhibit the ability to adsorb electrolytes such as Na+, K+, and P; the protein-bound uremic substances such as creatinine and homocysteine. Therefore, the adsorbent material containing the two-dimensional particles can adsorb various adsorbates, and application to an adsorbent sheet, a separation membrane, and an artificial dialysis machine using such an adsorbent material is expected.
In addition, it was confirmed that the two-dimensional particles of Examples 5 to 10 exhibited an action of adsorbing a disease-causing substance, particularly an electrolyte (ionic substance), a uremic substance, and other proteins. Therefore, the adsorbent material containing the two-dimensional particles can adsorb various adsorbates, and application to an adsorbent sheet, a separation membrane, and an artificial dialysis machine using such an adsorbent material is expected.
In Comparative Examples 1 to 3, predetermined two-dimensional particles were not contained, and as a result of the adsorption test, it was confirmed that the adsorbate was limited. In particular, it was not confirmed that any of the adsorbent materials of Comparative Examples 1 to 3 adsorbed an electrolyte such as Na+, K+, or P.
The present disclosure comprises the following:
[1] An adsorbent material used for adsorbing a disease-causing substance, the adsorbent material comprising two-dimensional particles having one or plural layers, the one or plural layers comprising a layer body represented by:
MmXn
wherein M is at least one metal of Group 3, 4, 5, 6, or 7, X is a carbon atom, a nitrogen atom, or a combination thereof, n is not less than 1 and not more than 4, m is more than n but not more than 5, and a modifier or terminal T exists on a surface of the layer body, wherein T is at least one selected from a hydroxyl group, a fluorine atom, a chlorine atom, an oxygen atom, and a hydrogen atom.
[2] The adsorbent material according to [1], wherein the disease-causing substance contains a protein.
[3] The adsorbent material according to [1] or [2], wherein the disease-causing substance contains a uremic substance having a molecular weight of 100 or more.
[4] The adsorbent material of [3], wherein the uremic substance comprises β2-microglobulin.
[5] The adsorbent material according to any one of [1] to [4], wherein the disease-causing substance contains a cytokine.
[6] The adsorbent material according to [5], wherein the cytokine comprises at least one selected from interleukins, interferons, a chemokine, a hematopoietic factor, a cell growth factor, and a tumor necrosis factor.
[7] The adsorbent material according to any one of [1] to [6], wherein the disease-causing substance contains an electrolyte.
[8] The adsorbent material according to [7], wherein the electrolyte contains at least one selected from Na+, K+, Mg2+, Ca2+, and PO43−.
[9] An adsorbent sheet comprising the adsorbent material according to any one of [1] to [8].
[10] A separation membrane comprising the adsorbent material according to any one of [1] to [8].
[11] An artificial dialysis machine comprising the adsorbent material according to any one of [1] to [8].
[12] A method for producing an adsorbent material used for adsorption of a disease-causing substance, the method comprising:
MmAXn
| Number | Date | Country | Kind |
|---|---|---|---|
| 2022-070348 | Apr 2022 | JP | national |
| 2022-112701 | Jul 2022 | JP | national |
| 2022-163375 | Oct 2022 | JP | national |
The present application is a continuation of International application No. PCT/JP2023/015824, filed Apr. 20, 2023, which claims priority to Japanese Patent Application No. 2022-070348, filed Apr. 21, 2022, Japanese Patent Application No. 2022-112701, filed Jul. 13, 2022, International application No. PCT/JP2022/037909, filed Oct. 11, 2022, and Japanese Patent Application No. 2022-163375, filed Oct. 11, 2022; and is a continuation of International application No. PCT/JP2022/037909, filed Oct. 11, 2022, which claims priority to Japanese Patent Application No. 2022-070348, filed Apr. 21, 2022; the entire contents of each of which are incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/JP2023/015824 | Apr 2023 | WO |
| Child | 18915818 | US | |
| Parent | PCT/JP2022/037909 | Oct 2022 | WO |
| Child | 18915818 | US |
