JPH06296859A - Coated carrier - Google Patents

Abstract

PURPOSE:To provide a coated carrier for an adsorbent which does not have non-singularity adsorption of lipid or protein and fix a large number of ligands easily and stably with a superb compatibility with a body fluid such as blood and an outstanding adsorptive capability. CONSTITUTION:The subject coated carrier consists of a high-molecular coated layer formed on the surface of a solid fibrous film-like porous carrier of an adsorbent made from an organic synthetic high-molecular material.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION Adsorbents are used to adsorb components in solutions, especially body fluids. The present invention relates to a porous carrier useful for this adsorbent.

[0002]

2. Description of the Related Art In order to adsorb a substance dissolved in a solution, an adsorbent in which a molecule having an affinity for the substance is insolubilized on the surface of a porous carrier is used in the fields of medicine, industry, analysis, etc. Widely used in the field of basic research. As the porous carrier, spherical or bead-shaped porous carriers made of materials such as cellulose, dextran, chitosan, and styrene / divinylbenzene are often used. Particularly in the medical field, a molecule that selectively binds to a pathogen, that is, an adsorbent having a ligand in a porous carrier is used,
It is used in a treatment method, for example, an extracorporeal circulation treatment, in which a body fluid such as blood or plasma of a patient taken out of the body is brought into contact with an adsorbent to adsorb and remove a pathogenic substance in blood and then returned to the patient. For example, a bead-like porous carrier made of cellulose and covalently bound dextran sulfate, a bead-like porous carrier made of polyvinyl alcohol and tryptophan covalently bonded thereto, and the like. These bead-shaped porous carriers have problems that it is difficult to pack them closely and the priming volume is large. For the purpose of solving this problem, a fibrous porous adsorbent is known (JP-A-60-24).
6765). The fibrous porous adsorbent shown in the invention solves the problems of the adsorbent using the above bead-shaped carrier, but according to the study of the present inventors, porous glass fiber etc. Since the porous carrier of the present invention has a large amount of nonspecific adsorption of lipids and proteins, it was unsuitable for use as a selective or specific adsorbent by immobilizing a ligand on the surface. Furthermore, since it is difficult to introduce a functional group onto the surface and the types of functional groups that can be introduced are limited, there is no versatility, and there is a problem as a carrier for stably immobilizing a ligand. Also, the amount of adsorbed substance adsorbed per unit volume of adsorbent, that is, the adsorption performance is determined by how much surface area the porous support can contact and adsorb the adsorbed substance. The surface area is the sum of the external surface area and the internal surface area of the adsorbent carrier, but in the conventional bead-shaped carrier, the pore diameter is increased or the number of pores is increased in order to increase the internal surface area.
Unlike the present invention, the pores obtained with the bead-shaped carrier do not substantially penetrate, and become smaller from the surface to the inside, so that the pores are blocked by the adsorbed substance adsorbed in the pores and contain more adsorbed substances. There is a problem that the body fluid cannot flow in, or the body fluid containing the substance to be adsorbed that enters the body is limited due to diffusion. Further, if the particle diameter of the bead-shaped carrier is reduced for the purpose of increasing the external surface area, the liquid resistance becomes large, and further, the particles may flow out of the column, which is dangerous. In other words, there is a limit to the increase in surface area that can be effectively used.

[0003]

The object of the present invention is to achieve non-specific adsorption of lipids and proteins, excellent compatibility with body fluids such as blood, and easy and stable immobilization of many ligands.
It is intended to provide a coated carrier for an adsorbent having excellent adsorption ability.

[0004]

The gist of the present invention is as follows. A coated carrier having a polymer coating layer on the surface of a solid fiber membrane-like porous carrier for an adsorbent made of an organic synthetic polymer material. The present invention will be described below item by item.

Definition of internal surface area: The total surface area of all pores in a porous carrier.

Definition of coated carrier The coated carrier as referred to in the present invention means a large number of pores opened on the surface for making an adsorbent by insolubilizing a molecule having an affinity for a target substance, that is, a ligand. A porous carrier having pores, the length of which in the longitudinal direction is sufficiently long with respect to the thickness, and the surface of a thread-like or fibrous solid fiber membrane porous support is coated with a hydrophilic material. Say something. The coated carrier may have a cross section of any shape such as a circle, an ellipse, a polygon, and a star. Furthermore, the central portion of the cross section does not have a hole penetrating in a substantially same shape along the longitudinal direction.
The hole penetrating in the central part of the cross section along the longitudinal direction with substantially the same shape is separated by the membrane from the outside of the hollow fiber, which the hollow fiber membrane has, for example, is continuously formed during spinning. Refers to the internal space, etc., and does not refer to those formed irregularly by the continuity of pores.

Definition of hydrophilic coating layer The hydrophilic coating layer as used in the present invention is a hydrophilic coating layer that substantially covers the solid fibrous membrane-like porous support in order to improve the affinity with an aqueous solution or blood. It is a polymer, and the contact angle of water droplets on the surface when formed into a flat plate, which is determined by the contact angle measurement method, is 8
It is preferably 0 degree or less, and when the polymer is exemplified by the name as a monomer of the polymer unit, hydroxystyrene, hydroxymethylstyrene, vinyl alcohol, 2
-Hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, vinylamine, diethylaminoethylstyrene, diethylaminoethyl methacrylate, methoxytriethylene glycol methacrylate, dimethylaminoethyl (meth) acrylate segmented polyurethane, segmented polyester and other block copolymers, polyethylene oxide Examples include graft copolymers such as chain-containing monomers and other polymerized monomers, ethylene-vinyl alcohol, polyesters, polyethylene glycols, and the like.

It is particularly preferred that the polymer has a hydroxyl group. There is no particular limitation on the bonding mode of the hydroxyl group in the polymer. Among these polymers, ethylene-vinyl alcohol, polyethylene glycol, methoxytriethylene glycol methacrylate is preferable in terms of hydrophilic effect, particularly ethylene-vinyl alcohol is easy to introduce an active group when introducing a basic functional group,
In addition, the hydrophilicity is less likely to decrease due to peeling when the basic functional group is introduced, which is more preferable. The hydrophilic coating layer may be a homopolymer of the above polymer units, or may be a copolymer of two or more polymers, and may be a polymer such as a linear polymer, a graft polymer or a crosslinked polymer. Has nothing to do with.

Method for Obtaining Coating Layer A method for obtaining a hydrophilic coating layer on a porous support is to immerse the porous support in a liquid in which the compound forming the coating layer is dissolved,
Alternatively, a method of coating by spraying the liquid, a method of covalently bonding to the surface of the porous support by a graft method using radiation or an electron beam, or a method of chemical sharing through a functional group on the surface of the porous support There are ways to combine them. Among them, the coating method is industrially easy and advantageous. The coating method referred to here may be a method in which a polymerizable compound is also allowed to coexist in the compound forming the coating layer and crosslinking is performed after coating. The amount of the coating layer thus obtained, that is, the coating amount, is expressed by the weight of the coating layer per the surface area of the coated carrier, and is 10 ⁻⁵ g /
It is at least m ² and at most 1 g / m ² . The coating amount is 10 ^-5
If it is less than g / m ² , hydrophilicity is insufficient and the effect as a hydrophilic coating layer cannot be obtained. If the coating amount is more than 1 g / m ² , the pores of the support are clogged to give a porous carrier. It is not preferable because it cannot be used. A particularly preferred amount of this coating layer is 10 ^-4 g / m ² or more and 10 ^-1 g / m ² or less.

Pore size The pore size and pore volume of the coated carrier can be obtained from the mercury pressure curve by the mercury intrusion method. It is preferable that the pores referred to here have a value in a state as close to practical use as possible, and a value when used as an adsorbent. Also, if the shape changes due to the drying process during the measurement with the mercury porosimetry, the change in the diameter of the coated carrier is measured, and the surface area is the square of the change rate of the diameter of the coated carrier, and the pore volume is the cube of the diameter of the coated carrier. It was decided to double the correction. That is, when the diameter of the coated carrier becomes 1 / X times, the surface area becomes 1 / X ²
And the pore volume is 1 / X ³ times. The average pore size of the coated carrier is determined by dividing the total pore volume by the total pore surface area, assuming that the pores are cylindrical. Any average pore diameter can be used, but if it is less than 0.01 μm, the substance to be adsorbed does not sufficiently penetrate into the inside of the coated carrier, and a sufficient adsorption ability cannot be obtained, and if it exceeds 10 μm. However, the risk that the strength is lowered and the material is likely to be deformed is increased, and the total surface area is probably small so that a sufficient adsorption capacity cannot be obtained, which is not preferable in practical use. Preferable average pore diameter is 0.01 μm or more and 10 μm
m or less. The thickness is preferably 0.05 μm or more, and most preferably 0.1 μm or more. It is more preferably 5 μm or less, and most preferably 2 μm or less.

Pore shape The pores are circular, elliptical, rectangular, star-shaped, polygonal, amorphous,
It may have any other shape, but it may be circular, oval,
The strip shape is more preferable in terms of the ease with which the substance to be adsorbed enters the inside of the coated carrier. Further, it is highly preferable that the pores are through-holes regardless of the shape of the pores, because the ligand can be uniformly insolubilized even inside the support, and the substance to be adsorbed can easily enter the inside of the adsorbent.

Pore size distribution With the coated carrier of the present invention, more uniform pores can be obtained from the fiber surface to the central portion, and the pores can be effectively used for adsorption to the inside. An attempt to make a pore size distribution and effectively utilize the inside is not particularly important. For the coated carrier, a sharp pore size distribution is more preferable because a larger effective surface area can be secured per unit volume of the adsorbent. Therefore, 0.01 μm or more 10
The volume of pores having a diameter of μm or less is preferably 40% or more of the total pore volume, and more preferably 70% or more. Furthermore, the volume of pores with a diameter of 0.05 μm or more and 5 μm or less is 4
It is more preferably 0% or more. It is more preferably 70% or more, and most preferably a very sharp distribution of 80%.

Total Surface Area The total surface area based on the dry weight of the coated carrier of the present invention is particularly preferably 1 m ² / g or more, more preferably 5 m ² / g or more, further preferably 10 m ² / g or more. is there. Obviously, the larger the total surface area, the higher the adsorption capacity, but when used as a porous support for an adsorbent for extracorporeal circulation treatment, if the total surface area becomes too large, substances other than the adsorption target substance The risk of non-specific adsorption also increases. Particularly when used for blood or body fluid, many useful trace proteins coexist, and it is not preferable that the nonspecific adsorption amount of these proteins increases. Therefore 50
Is preferably 0 m ² / g or less, and more preferably not more than 300 meters ² / g, most preferably 150 meters ²
/ G or less.

Method for Measuring Pore Size, Pore Size Distribution, Surface Area The pore size and pore size can be determined by the mercury intrusion method and the mercury intrusion curve. The surface area can also be calculated from the amount of adsorption using a gas such as nitrogen,
(BET method) Since the surface area can be obtained in comparison with the pore size distribution, it is preferable to determine it by the mercury intrusion method like the pore size. The specific pore diameter, pore diameter distribution, and surface area can be measured using a mercury porosimeter (manufactured by Shimadzu Corporation, Micromeritics Pore Size 9320). Pore Plot System (Shimadzu Corporation, 9320)
-PC2 (V1.0)) to analyze the pore size, pore size distribution,
The surface area can be determined. At this time, the pressure range of mercury was 1 to 30,000 psia.

Pore Volume The total pore volume of the coated carrier is 0.1 ml / g or more and 5 when expressed as the total amount of the pore volume per dry weight of the coated carrier.
It is preferably 0 ml / g or less. If the total pore volume is less than 0.1 ml / g, the surface area that works effectively in practice will be small, and sufficient adsorption capacity cannot be obtained. If the total pore volume exceeds 50 ml / g, the strength of the coated carrier becomes low, which is not preferable in use. A more preferable range of the total pore volume of the coated carrier is 0.5 ml / g or more and 30 ml / g or less, and more preferably 1 ml / g or more and 10 ml / g or less.

Shape of Carrier The length in the longitudinal direction of the coated carrier is not particularly limited as long as it is substantially longer than the thickness, that is, the diameter, but it is preferably 50 mm or more from the viewpoint of handleability. . If the diameter is too thin, the coated carrier will be easily cut and the handling will be poor, and if it is too thick, the adsorption ability will probably be low because the substance to be adsorbed will probably not be able to easily penetrate into the coated carrier. The resulting diameter is preferably 1 μm or more and 10 mm or less, more preferably 10 μm or more and 1 mm or less. Particularly preferably, it is 50 μm or more and 300 μm or less.

Support Material The material used for the support of the coated carrier has excellent stability of the support itself, no eluate, little change in shape between dry and wet states, and ligand immobilization on the surface of the support. Since it can be easily and efficiently carried out by various methods, organic synthetic polymer materials are preferable. Specific examples of the organic synthetic polymer material include nylon resins such as nylon 6 and nylon 66, polyacetal resins, polycarbonate resins, modified polyphenylene oxide resins, polybutylene terephthalate,
Polyethylene terephthalate, polyphenylene sulfide, diallyl phthalate, polyimide, polyamide imide, polymethylpentene, hollisulphone, polyether sulfone, polyacrylate, polyether ester ketone, polytetrafluoroethylene, polyethylene, polypropylene, polyvinyl chloride, polystyrene,
Examples thereof include any one of phenol, epoxy, polyurethane, polyvinyl acetal, viscose, ABS, ethylene vinyl alcohol, rubber urea resin, cellulose, cellulose acetate, and polymethacrylate, or a copolymer containing them. Among them, polyolefins such as polyethylene and polypropylene, polysulfone, and polymethylmetaacrylate are easy to form into a solid fiber membrane and easy to form preferable pores, and also from the viewpoint of flexibility. Further, a polymer material containing cellulose as a component is more preferable, and a polyolefin polymer material such as polyethylene or polypropylene is particularly preferable because a strip-shaped through hole can be obtained.

Manufacturing Method For manufacturing the solid fibrous film-like porous support, a foaming agent decomposition method using an organic or inorganic foaming agent that decomposes at a specific temperature to generate nitrogen gas, carbon dioxide gas, etc. Solvent vaporization method, in which a solvent is added and mixed at the raw material stage, and the solvent is vaporized and foamed during synthesis, gas mixing method in which a gaseous foaming agent is mechanically mixed and foamed in the normal state, and chemistry that uses gas generated in the polymerization process Reaction method, elution method in which soluble substance is dissolved in polymer material and then eluted, sintering method in which powder particles are bonded to each other by a sintering action below melting temperature, wet phase conversion method, melt phase separation method, melt spinning drawing An opening method or the like can be used. Among them, the wet phase conversion method, the melt phase separation method, and the melt spinning draw opening method are preferable because a support having a preferable fiber diameter is easily obtained.
In particular, it is easy to obtain a solid fiber film shape, and since no solvent or other additives are used in the polymer material, there is no problem of residual solvent, etc. A stretch-opening method is particularly preferred in which after forming, the crystal lamellae are split by cold stretching and the pore size is further expanded by hot stretching to form a porous structure composed of stacked lamellae and microfibrils. When the pores have a porous structure composed of stacked lamellae and microfibrils, the flow resistance of the solution into the porous structure is low, so that the immobilization of the ligand inside the solid fiber membrane porous support is uniform to the inside. It is particularly preferable because it can be used as an adsorbent and can be effectively used as an adsorbent even inside.

Kind of Ligand The coated carrier can be used by insolubilizing a substance having an affinity for the target substance to be adsorbed, that is, the ligand, on the surface of the coated carrier or through the coating layer. As the ligand, a known synthetic compound having an affinity for the adsorption target substance or a natural substance can be used. For example, anti-low density lipoprotein antibody, tryptophan, acetylcholine receptor-derived polypeptide, phenylalanine, Torpedo-derived polypeptide, blood group (A type, B type) antigen, protein A, trimethylammonium group, dimethylammonium group, aspartame,
Examples thereof include polymyxin B, anti-immunoglobulin antibody, anti-leukocyte differentiation antigen antibody such as anti-CD8 antibody and anti-CD4 antibody, anti-cytokine antibody such as anti-cancer necrosis factor antibody, anti-endotoxin antibody, single-stranded or double-stranded DNA and the like. Further, of these, two or more kinds of ligands may be insolubilized. The molecular weight of these ligands may be any molecular weight, but from the practical point of view, 1,000,000 or less is easily available.

Method for immobilizing a ligand The method for insolubilizing a ligand in a coated carrier includes a method in which a ligand and a hydrophilic coating layer are allowed to coexist on the surface of a porous support, or a ligand formed on a surface of a previously formed coated carrier via a coating layer. There is a method of insolubilizing. For example, by coating the coated carrier in a liquid in which the ligand is dissolved, or by spraying the liquid, a method of covalently bonding by a chemical method or a grafting method using radiation or an electron beam, or a chemical method. There are methods such as a covalent bond via a functional group. Among these, it is preferable to use a graft method or a covalent bond method via a functional group to covalently bond the ligand, because there is no risk of ligand elution during use.
Among these, according to the research conducted by the present inventors, it is most preferable to covalently bond a ligand to the surface of the coating layer because the adsorption ability is high and the production is easy.

Carrier Activation Method As an example of a method for obtaining a functional group on the coated carrier, a cyanogen halide method, an epichlorohydrin method, an epibromhydrin method, a bisepoxide method, a bromoacetyl bromide method, a tresyl chloride method, a bromoacetamide method. The law is known. Specific examples include an amino group, a carboxyl group, a hydroxyl group, a thiol group, an acid anhydride group, a succinylimide group, a chlorine group, an aldehyde group, an amide group, an epoxy group and a tresyl group. Of these, epoxy groups derived from the epichlorohydrin method and the epibromhydrin method are particularly preferable because of their stability during heat sterilization.

Ligand-immobilized amount The amount of the ligand to be introduced is not particularly specified, but if it is too small, the adsorption capacity is low, and if it is too large, there is a risk of liberation of the ligand at the time of use. It is preferable that the volume is 1 ng / ml or more and 100 mg / ml or less. Further, a more preferable range is 1 μg / ml or more and 100 μg / ml or less.

Uses The coated carrier is used for adsorbing a dissolved substance in water or an organic solvent, and is particularly suitable as a support for an adsorbent for proteins, sugars, nucleic acids, hormones, lipids, cytokines and the like in body fluids such as blood. . Most preferably, it can be used as a carrier of a selective or specific adsorbent for clinical extracorporeal circulation treatment. Clinically, the use of selective or specific adsorption for extracorporeal circulation treatment includes bile acid, amyloid precursor protein A, cancer necrosis factor, bilirubin, bilirubin-conjugated albumin, endotoxin, anti-cardiolipin antibody, anti-acetylcholine receptor antibody, low density and / or Or very low density lipoprotein, sulfatide-adhesive protein, activated complement component, amyloid protein A, immune complex, anti-blood group antibody, anti-platelet antibody, auto-antibody such as anti-DNA antibody and rheumatoid factor, and / or
Alternatively, there may be mentioned immune B cells, T cells, immunoglobulin L chains, blood coagulation factor VIII, blood coagulation factor IX, β ₂ microglobulin, etc. which produce the autoantibody.

Method of Use The adsorbent obtained by insolubilizing the ligand on the coated carrier can be used as it is, or cut into short pieces, or made into cotton and packed in a container to be used as a column. Alternatively, the adsorbent that has been processed into a woven or non-woven fabric can be used as a column by, for example, stacking the woven or non-woven fabric into a flat plate or rolling it into a cylinder and filling the container. Alternatively, a part of the adsorbent obtained by insolubilizing the ligand in the coated carrier can be fixed to the container with an adhesive or the like before use. Further, two or more kinds of adsorbents may coexist in layers or randomly. The container may have an inflow port and an outflow port for the solution to be adsorbed, and may have a structure in which the adsorbent does not substantially flow out. At this time, the ratio of the adsorbent volume to the total inner volume of the container is preferably 20% or more and 90% or less, and 40% or more and 80% or less is particularly excellent when the more preferable range is taken into consideration. In actual use, blood may be directly perfused, or plasma obtained by previously separating by a centrifugation method or a membrane method may be perfused. At this time, blood or plasma may be continuously perfused or intermittently perfused. In particular, the adsorbent obtained by insolubilizing the ligand in the coated carrier of the present invention is a fiber bundle, and both ends of the bundle are kept in a bundle shape using urethane or silicone adhesive, and fixed to the container. In this case, it has excellent platelet permeability and can be preferably used for the purpose of directly perfusing blood. At this time, the bundle may be fixed to the container by the adhesive, or may be fixed by a physical method using the container structure.

[0025]

The coated carrier of the present invention does not have non-specific adsorption of lipids and proteins, is excellent in compatibility with body fluids such as blood, and uses a solid fiber membrane having a uniform through hole in a porous body. The body fluid containing the substance to be adsorbed into and out of the pores can freely flow in and out, the internal pore area can be effectively utilized, and at the same time, it can be operated without resistance to permeation, and at the same time, many ligands can be immobilized easily and stably.

【Example】

[0026]

Example 1 High-density polyethylene (density 0.968, M
I value of 5.5, brand name Hi-Zex 2208J) using a circular spinneret with a spinneret diameter of 10 mm, spinning temperature of 150 ° C., polyethylene discharge rate of 8 g / min, spinning distance of 5 m, spinning cooling temperature of 25 ° C., winding tension of 3 gf. , Winding speed 260m /
And melt-spun. The draft ratio at this time is 7,000
Met. After spinning, it was annealed at 115 ° C. for 2 hours.
The obtained polyethylene yarn was cold-drawn at room temperature (24 ° C.) at a primary roller speed of 1.5 m / min and a secondary roller speed of 2 m / min. The cold draw ratio at this time was about 1.3 times. Next, at three consecutive temperatures of 108 ° C., 119 ° C. and 122 ° C., roller speeds of 6 m / min and 7.8, respectively.
A polyethylene porous support having a solid fiber membrane-like porous structure was obtained by hot drawing at a drawing speed of m / min and 8.7 m / min for drawing and opening. The total draw ratio of the porous support is 5.8 times,
The yarn diameter was 162 μm and the winding length was 15 km. This porous support was prepared by adding 1.0% of an ethylene / vinyl alcohol copolymer having an ethylene content of 30 mol% to an aqueous ethanol solution.
The coated carrier having a hydrophilic coating layer of an ethylene / vinyl alcohol copolymer was obtained by immersing in a liquid having a weight% dissolved therein. The coated carrier has an average pore size of 0.42 μm, a total pore volume of 4.4 ml / g, a porosity of 80.0%, and a total surface area of 2 according to the mercury intrusion method.
The volume of pores having a pore size of 9.1 m ² / g and a pore diameter of 0.01 μm or more and 10 μm or less was 93% of the total pore volume. Then, the coated carrier (cut to a length of 10 cm, 800 pieces) was added to 40 ml of a mixed solution of 5 volumes of dimethyl sulfoxide, 4 volumes of epichlorohydrin and 1 volume of 10N sodium hydroxide aqueous solution in 40 ml.
The reaction was performed at 2 ° C. for 2 hours to introduce an epoxy group. Phenylalanine was reacted with a coated carrier having an epoxy group introduced therein in a 0.1N sodium hydroxide aqueous solution to obtain a phenylalanine-immobilized adsorbent. The fixed amount of phenylalanine was 71 μeq / ml of the adsorbent. The phenylalanine fixed adsorbent has an average pore diameter of 0.22 μm measured by mercury porosimetry.
Total pore volume 3.9 ml / g, total surface area 66.1 m ² /
The amount of the coating layer was 3.0 × 10 ⁻³ g / m ^{2 as} determined from the change in weight before and after the immersion treatment. Nonspecific adsorption is measured by a phenylalanine fixed adsorbent 200 having a length of 10 cm.
Soak the book in 6 ml of rheumatism patient's plasma and shake for 3
The reaction was carried out at 7 ° C. for 2 hours. Rheumatoid factor is R
It was measured by the A test method. The reduction rate of the total amount of each plasma component before and after the reaction was determined as the adsorption rate. Rheumatoid factor, albumin, IgG, transferrin, total cholesterol,
Fibrinogen, calcium ion, chlorine ion adsorption rate of 50.0%, 2.6%, 9.1%,
4.2%, 1.7%, 8.8%, 0.3%, 0%, showing high adsorbability for rheumatoid factor, which is the target substance for adsorption, and non-specificity of other plasma components. No adsorption was seen.

[0027]

Example 2 High-density polyethylene (density 0.968, M
I value 5.5, trade name Hi-Zex 2208J) using a circular spinneret with a spinneret diameter of 35 mm, spinning temperature 150 ° C., polyethylene discharge rate 16 g / min, spinning distance 5 m, spinning cooling temperature 24 ° C., winding tension 10 gf , Winding speed 400
Melt spinning was performed at m / min. The draft ratio at this time is 24,
It was 000. After spinning, it was annealed at 115 ° C. for 2 hours. The obtained polyethylene yarn at room temperature (24 ° C),
Primary roller speed 3.75 m / min, secondary roller speed 5
Cold drawing was performed at m / min. The cold draw ratio at this time was about 1.3 times. Next 108 ° C, 119 ° C, 122 ° C continuously
Roller speed of 15m /
Min., 19.5 m / min, and 21.8 m / min, and drawn at a drawing speed to draw holes to obtain a polyethylene porous support having a solid fiber membrane-like porous structure. The total draw ratio of the porous support was 5.8 times, the yarn diameter was 176 μm, and the winding length was 15 km. This porous support was immersed in a solution of polyhydroxyethyl methacrylate (molecular weight: about 50,000) dissolved in 1.0% by weight of an aqueous methanol solution to obtain a coated carrier having a hydrophilic coating layer of polyhydroxyethyl methacrylate. . The amount of the coating layer determined from the weight change before and after the immersion treatment was 1.8 × 10 ⁻³ g / m ² . The coated carrier (10 cm in length, 100 pieces) was immersed in a solution of diethylamine dissolved in a 10% aqueous ethanol solution at a concentration of 30%,
Irradiation with γ-rays was carried out at 25 kGy. After the irradiation, it was thoroughly washed to obtain an adsorbent having a diethylammonium group on the surface. The porous support has an average pore size of 0.17 μm, a total pore volume of 3.3 ml / g, a porosity of 77.0%, a total surface area of 49.1 m ² / g, a pore size of 0.01 μm or more and 10 μm or less, as determined by mercury porosimetry. The pore volume was 88% of the total pore volume. Example 1
Non-specific adsorption was measured using plasma of liver failure patient in the same manner as in Example 1. Total bilirubin, albumin, Ig
Adsorption rates of G, transferrin, total cholesterol, fibrinogen, calcium ion, and chloride ion are 62.4%, 3.1%, 3.3%, 5.5%, respectively.
0.3%, 4.7%, 0.1% and 06%, showing high adsorbability for total bilirubin, which is the target substance to be adsorbed,
Moreover, non-specific adsorption of other plasma components was not observed.

[0028]

Example 3 700 adsorbents of Example 1 (filling rate 35
%) Was adsorbed side by side in a cylindrical container made of polycarbonate having an inner diameter of 8 mm and a length of 10 cm in the length direction of the container, and both ends of the adsorbent were bonded and fixed together with the container by urethane. At this time, both ends of the container were sealed with urethane. The container had a side entrance and an exit. The entrance and exit were not blocked by urethane on both ends, and were located farthest from each other. The adsorber was obtained as described above. Then, the obtained adsorber was used to evaluate the direct perfusion of blood. Normal human blood was collected in the presence of ACD-A1 / 9 as an anticoagulant. 40 ml of this blood was transferred to the adsorber.
When perfusion was performed at 2 ml / min and the number of platelets in the effluent of the adsorber was measured, the reduction rate of platelets was 9.7%, which was extremely low, indicating excellent platelet passage properties.

Claims (8)

[Claims] 1. A coated carrier having a polymer coating layer on the surface of a solid fibrous film-like porous carrier for an adsorbent made of an organic synthetic polymer material. 2. The coated carrier according to claim 1, wherein the polymer coating layer is a hydrophilic synthetic compound having a hydroxyl group. 3. The coated carrier according to claim ^{2, wherein} the amount of the polymer coating layer is 10 ⁻⁵ g / m ² or more and 1 g / m ² or less. 4. The coated carrier according to claim 1, wherein the ligand substance is insolubilized by covalently bonding with the hydrophilic coating layer. 5. The coated carrier according to claim 1, which is for an adsorbent made of an organic synthetic polymer material having pores having an average pore diameter of 0.01 μm or more and 10 μm or less. 6. The total surface area is 1m ² / g or more 500m ² /
The coated carrier according to claim 1, which is not more than g. 7. The coated carrier according to claim 1, wherein the volume of pores having a pore diameter of 0.01 μm or more and 10 μm or less is 40% or more of the total pore volume. 8. The coated carrier according to claim 1, which comprises a polyolefin.