JP3353945B2 - Coated carrier - Google Patents

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 the adsorbent.

[0002]

2. Description of the Related Art In order to adsorb a substance dissolved in a solution, an adsorbent obtained by insolubilizing a molecule having an affinity for the substance on the surface of a porous carrier is used in fields such as medical and industrial fields and analysis. Widely used in the field of basic research. As the porous carrier, a spherical or bead-shaped porous carrier made of a material such as cellulose, dextran, chitosan, and styrene / divinylbenzene is often used. Particularly in the field of medicine, using an adsorbent having a molecule that selectively binds to a pathogen, that is, a ligand on a porous carrier,
It is used in a treatment method in which a bodily fluid such as blood or plasma of a patient taken out of the body is brought into contact with an adsorbent, and a pathogenic substance in the blood is adsorbed and removed and returned to the patient again, for example, extracorporeal circulation treatment or the like. For example, those obtained by covalently binding dextran sulfate to a bead-shaped porous carrier made of cellulose, those obtained by covalently binding tryptophan to a bead-shaped porous carrier made of polyvinyl alcohol, and the like. These bead-shaped porous carriers have problems such as difficulty in close packing and a large priming volume. For the purpose of solving this problem, a fibrous porous adsorbent is known (JP-A-60-24).
6765). Although the fibrous porous adsorbent disclosed in the present invention has solved the problems of the adsorbent using the above-described bead-shaped carrier, according to the study of the present inventors, it has been found that porous glass fibers and the like The porous carrier of the invention has many non-specific adsorptions of lipids and proteins, and is not suitable for use as a selective or specific adsorbent by immobilizing a ligand on the surface. Furthermore, it is difficult to introduce a functional group into the surface, and the types of functional groups that can be introduced are limited, so there is no versatility, and thus there is a problem as a carrier for stably fixing a ligand. Further, the amount of adsorbed substance per unit volume of adsorbent, that is, the adsorption performance is determined by how much the porous support has a surface area capable of contacting and adsorbing the adsorbed substance. Although the surface area is the sum of the external surface area and the internal surface area of the adsorbent carrier, in the conventional bead-shaped carrier, the pore size is increased for the purpose of increasing the internal surface area, or the number of pores is increased.
Unlike the present invention, the pores obtained from the bead-shaped carrier do not substantially penetrate, and become smaller from the surface to the inside, so that they are blocked by the substance to be adsorbed adsorbed in the pores and contain more substances to be adsorbed. There is a problem that the bodily fluid cannot flow in or the bodily fluid containing the substance to be adsorbed which enters into the inside is limited by diffusion and is limited. Further, if the particle diameter of the bead-shaped carrier is reduced for the purpose of increasing the external surface area, the flow resistance increases, and furthermore, there is a danger that particles may flow out of the column. That is, there is a limit to the increase in the surface area that can be used effectively.

[0003]

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

[0004]

The gist of the present invention is as follows. On the surface of the actual fiber 維状 porous carrier in the adsorbent for made of an organic synthetic polymer material a coated carrier having a polymer coating layer, the pore shape of the middle actual fibrous porous carrier
A coated carrier having a shape of a through hole . less than,
The present invention will be described 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 used in the present invention refers to a large number of pores formed on the surface for insolubilizing a molecule having an affinity for a target substance, that is, a ligand, on the surface to make it an adsorbent. A porous support having pores, the length of which is sufficiently long in the longitudinal direction with respect to the thickness. The surface of a fibrous or fibrous solid fiber membrane-like porous support is coated with a hydrophilic material. Say things. The cross-section of the coated carrier may be any shape such as a circle, an ellipse, a polygon, and a star. Furthermore, there is no hole penetrating substantially in the same shape along the longitudinal direction in the center of the cross section.
At the center of the cross section, a hole penetrating in substantially the same shape along the longitudinal direction is separated from the outside of the hollow fiber by the hollow fiber membrane, for example, which is formed continuously during spinning. Refers to an internal space or the like, and does not refer to anything that is irregularly formed by continuation of pores.

Definition of hydrophilic coating layer The hydrophilic coating layer referred to in the present invention is a hydrophilic coating that substantially covers a solid fiber 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 it is formed into a flat plate determined by a contact angle measurement method is 8
It is preferably 0 ° or less, and when a polymer is exemplified by a monomer as a polymer unit, hydroxystyrene, hydroxymethylstyrene, vinyl alcohol,
-Hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, vinylamine, diethylaminoethylstyrene, diethylaminoethyl methacrylate, methoxytriethylene glycol methacrylate, dimethylaminoethyl (meth) acrylate segmented polyurethane, block copolymer such as segmented polyester, polyethylene oxide Examples thereof include a graft copolymer such as a monomer having a chain and another polymerizable monomer, ethylene-vinyl alcohol, polyester, and polyethylene glycol.

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

Method for Obtaining Coating Layer A method for obtaining a hydrophilic coating layer on a porous support includes immersing the porous support in a solution in which a compound for 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 grafting method using radiation or an electron beam, or a method of sharing via a functional group on the surface of the porous support by a chemical method There is a method of joining. Among them, the method of coating is particularly industrially easy and advantageous. The coating method referred to here may be a method in which a polymerizable compound is also present in a compound forming a coating layer, and crosslinking is performed after coating. The amount of the coating layer thus obtained, that is, the amount of coating, is expressed in terms of the weight of the coating layer per surface area of the coated carrier, 10 ⁻⁵ g /
m ² or more and 1 g / m ² or less. 10 ^-5 coverage
When the amount is less than g / m ² , the hydrophilicity is insufficient, and the effect as a hydrophilic coating layer cannot be obtained. When the amount exceeds 1 g / m ² , the pores of the support are clogged, and as a porous carrier, It is not preferable because it cannot be used. A particularly preferred amount of this coating layer is from 10 ^-4 g / m ^{2 to} 10 ^-1 g / m ² .

Pore size The pore size and pore volume of the coated carrier can be obtained from a mercury pressure curve by a mercury porosimetry. The pores mentioned here are preferably values in a state close to practical use as much as possible, and refer to values in a usage form as an adsorbent. When the shape changes due to the drying process at the time of measurement by the mercury intrusion method, the change in the diameter of the coated carrier is measured, and the surface area is the square of the rate of change in the diameter of the coated carrier, and the pore volume is the cube of the diameter of the coated carrier. It was decided to multiply and correct. That is, when the diameter of the coated carrier is 1 / X times, the surface area is 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 the average pore diameter is less than 0.01 μm, the substance to be adsorbed does not penetrate sufficiently into the interior of the coated carrier, and a sufficient adsorption capacity cannot be obtained. In addition, the danger of being easily deformed due to a decrease in strength is increased, and the total surface area is likely to be small, so that sufficient adsorption capacity cannot be obtained, which is not practically preferable. Preferred average pore size is 0.01 μm or more and 10 μm
m or less. It is preferably at least 0.05 μm, and most preferably at least 0.1 μm. It is more preferably 5 μm or less, and most preferably 2 μm or less.

Pore shape The pores are circular, elliptical, strip-shaped, star-shaped, polygonal, irregular,
Any other shape may be used, such as circular, elliptical,
The strip shape is more preferable in terms of easy entry of the substance to be adsorbed into the inside of the coated carrier. Further, it is very preferable that the through-holes are used regardless of the pore shape, because the ligand can be uniformly insolubilized into the support and the substance to be adsorbed can easily enter the adsorbent.

Pore size distribution The pore size of the coated carrier of the present invention is broad as in the case of a bead-shaped porous carrier because more uniform pores can be obtained from the fiber surface to the center and can be effectively used for internal adsorption. Attempts to make the pore size distribution and use it effectively inside are not particularly important. It is more preferable that the coated carrier has a sharp pore size distribution because a larger effective surface area can be secured per unit volume of the adsorbent. Therefore, 0.01 μm or more
The volume of the pore size of μm or less is preferably 40% or more of the total pore volume, more preferably 70% or more. Furthermore, the volume of the pore diameter of 0.05 μm or more and 5 μm or less is 4% of the total volume.
More preferably, it is 0% or more. More preferably, it is 70% or more, and most preferably, it has 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 preferably at least 1 m ² / g, more preferably at least 5 m ² / g, even more preferably at least 10 m ² / g. is there. It is obvious that the larger the total surface area is, the higher the adsorption capacity becomes.However, when used as a porous support of an adsorbent for extracorporeal circulation treatment, if the total surface area is too large, substances other than the target substance for adsorption will be removed. The risk of non-specific adsorption also increasing. In particular, when used for blood or body fluid, there are many useful trace proteins that coexist, and it is not preferable that the amount of nonspecific adsorption 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, and Surface Area Pore size and pore distribution can be determined by a mercury intrusion method and a mercury intrusion curve. The surface area can also be determined from the amount of adsorption using a gas such as nitrogen,
(BET method) Since a surface area in comparison with the pore distribution is obtained, it is preferable to determine the surface area by the mercury intrusion method in the same manner as the pore diameter. The specific measurement of the pore size, pore size distribution, and surface area can be performed using a mercury porosimeter (Micromeritics pore size 9320, manufactured by Shimadzu Corporation). The measurement results were obtained using a pore plot system (manufactured by Shimadzu Corporation, 9320).
-PC2 (V1.0)), and the pore size, pore size distribution,
The surface area can be determined. At this time, the pressure range of the 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% or more in terms of the total pore volume per dry weight of the coated carrier.
It is preferably at most 0 ml / g. If the total pore volume is less than 0.1 ml / g, the surface area that works effectively for practical use is reduced, so that sufficient adsorption capacity cannot be obtained. On the other hand, if the total pore volume exceeds 50 ml / g, the strength of the coated carrier is lowered, which is not preferable for use. Further, the more preferable range of the total pore volume of the coated carrier is from 0.5 ml / g to 30 ml / g, more preferably from 1 ml / g to 10 ml / g.

Shape of Carrier The length of the coated carrier in the longitudinal direction is not particularly limited as long as it is substantially longer than the thickness, that is, the diameter, but is preferably 50 mm or more from the viewpoint of handleability. . If the diameter is too small, the coated carrier is easy to cut and the handleability deteriorates.If the diameter is too large, the adsorption capacity is likely to be low because the substance to be adsorbed is unlikely to enter the inside of the coated carrier, so the cross-sectional area is converted to a circle. The diameter at this time 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 is excellent in stability of the support itself, there is no eluate, there is little change in shape between dry and wet states, and ligand is immobilized on the surface of the support. Is preferably an organic synthetic polymer material because it can be easily and efficiently performed by various methods. 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, polymethyl pentene, holisulfone, polyether sulfone, polyacrylate, polyether ester ketone, polytetrafluoroethylene, polyethylene, polypropylene, polyvinyl chloride, polystyrene,
Examples include phenol, epoxy, polyurethane, polyvinyl acetal, viscose, ABS, ethylene vinyl alcohol, rubber urea resin, cellulose, cellulose acetate, polymer methacrylate, and copolymers containing these. Among these, polyolefins such as polyethylene and polypropylene, polysulfone, and polymethyl methacrylate are easy to form into a solid fiber membrane and easy to form preferable pores. Further, a polymer material containing cellulose as a component is more preferable, and a polyolefin polymer material such as polyethylene or polypropylene is most preferable since a rectangular through hole can be obtained.

Manufacturing Method In order to manufacture a solid fibrous membrane-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 diffusion method in which a solvent is added and mixed at the raw material stage and the solvent is diffused and foamed during synthesis, gas mixing method in which a gaseous foaming agent is mechanically mixed and bubbled in a normal state, chemistry using gas generated in the polymerization process Reaction method, dissolution method in which soluble substance is dispersed in polymer material and then eluted, sintering method in which powder is bonded to each other by sintering operation below melting temperature, wet phase inversion method, melt phase separation method, melt spinning and drawing An opening method or the like can be used. Among them, a support having a preferable fiber diameter is easily obtained, and a wet phase inversion method, a melt phase separation method, and a melt spinning and stretching method are preferable.
In particular, since a solid fiber membrane shape can be easily obtained, and there is no problem such as residual solvent because no solvent or other additives are used in the polymer material, the crystalline polymer is melt-spun into a fibrous shape. After molding, the stretch opening method is particularly preferred in which the crystal lamellas are cleaved by cold stretching and the porous structure composed of the stack dramella and microfibrils obtained by expanding the pore diameter by hot stretching is further formed. When the pores have a porous structure consisting of a stack dramella and microfibrils, the flow resistance of the solution into the porous structure is low, and the ligand is fixed uniformly inside the solid fibrous membrane porous support. It is particularly preferable because it can be effectively used as an adsorbent up to the inside.

Kinds of Ligands The coated carrier can be used after insolubilizing a substance having an affinity for the target substance to be adsorbed, that is, a ligand, on the surface of the coated carrier or via a coating layer. As the ligand, a known synthetic compound having an affinity for the target substance for adsorption or a natural substance can be used. For example, anti-low-density lipoprotein antibodies, tryptophan, polypeptides derived from acetylcholine receptor, phenylalanine, polypeptides derived from caviar rays, blood group (type A, type B) antigens, protein A, trimethyl ammonium group, dimethyl ammonium group, aspartame,
Examples 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- or double-stranded DNA, and the like. Further, two or more of these ligands may be insolubilized. The molecular weight of these ligands may be any molecular weight, but from the viewpoint of practicality, 1,000,000 or less is easy to use.

Ligand immobilization method The method of insolubilizing the ligand in the coated carrier includes a method in which the ligand and the hydrophilic coating layer coexist on the surface of the porous support, and a method in which the ligand is formed on the surface of the previously formed coated carrier via the coating layer. And the like. For example, a method of coating by dipping the coated carrier in a liquid in which a ligand is dissolved or spraying the liquid, a method of covalent bonding by a chemical or grafting method using radiation or an electron beam, or a chemical method There is a method of covalently bonding via a functional group. Among these, it is preferable to covalently bind the ligand, such as a grafting method or a covalent bonding method via a functional group, because there is no danger of elution of the ligand during use.
Among these, according to the study of the present inventors, it is most preferable that the ligand is covalently bonded to the surface of the coating layer because the adsorption ability is high and the production is easy.

Carrier activating method One example of a method for obtaining a functional group on the coated carrier is a cyanogen halide method, epichlorohydrin method, epibromohydrin method, bisepoxide method, bromoacetyl bromide method, tresyl chloride method, 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. Among them, an epoxy group derived by an epichlorohydrin method, an epibromohydrin method, or the like is particularly preferable because of stability during heat sterilization.

The amount of immobilized ligand is not particularly limited. However, if the amount is too small, the adsorption capacity is low, and if the amount is too large, there is a risk that the ligand will be released during use. It is preferably from 1 ng / ml to 100 mg / ml per contained volume. Furthermore, a more preferable range is 1 μg / ml or more and 100 μg / ml or less.

Uses The coated carrier is used for the adsorption of dissolved substances in water or organic solvents, and is particularly suitable as a support for adsorbents such as proteins, sugars, nucleic acids, hormones, lipids and cytokines in body fluids such as blood. . Most preferably, it can be used as a carrier of a selective or specific adsorbent for treatment of extracorporeal circulation in clinical practice. Examples of the use of selective or specific adsorption for the treatment of extracorporeal circulation in the clinic include bile acids, amyloid precursor protein A, cancer necrosis factor, bilirubin, bilirubin-conjugated albumin, endotoxin, anti-cardiolipin antibodies, anti-acetylcholine receptor antibodies, low-density and / or Or autoantibodies such as very low density lipoprotein, sulfatide adhesion protein, activated complement component, amyloid protein A, immune complex, anti-blood group antibody, anti-platelet antibody, anti-DNA antibody and rheumatoid factor, and / or
Or immune B cells that produce the autoantibodies, T-cells, immunoglobulin L chain, blood coagulation factor VIII, blood coagulation factor IX, beta ₂ microglobulin, and the like.

Method of Use The adsorbent obtained by insolubilizing the ligand in the coated carrier can be used as a column as it is, cut into short pieces, or made into a cotton-like form, filled in a container, and used as a column. Alternatively, the adsorbent processed into a woven or nonwoven fabric can be used as a column by, for example, stacking the woven or nonwoven fabric into a flat plate or winding into a cylindrical shape and filling the container. Alternatively, a part of the adsorbent obtained by insolubilizing the ligand in the coated carrier may be used by fixing it to a container with an adhesive or the like. Further, two or more kinds of adsorbents may coexist in layers or randomly. The container may have an inlet and an outlet for the solution to be subjected to the adsorption treatment, 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 internal volume of the container is preferably 20% or more and 90% or less, and more preferably 40% or more and 80% or less in a more preferable range. In actual use, blood may be directly perfused, or plasma obtained by centrifugation or membrane separation in advance 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, the fibers are bundled, and both ends of the bundle are kept in a bundle shape using urethane or silicone adhesive, and are 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 a container structure.

[0025]

Industrial Applicability The coated carrier of the present invention uses a solid fiber membrane which has no nonspecific adsorption of lipids and proteins, has excellent compatibility with body fluids such as blood, and has a porous body having uniform through holes. The bodily fluid containing the substance to be adsorbed can freely enter and exit the pores, and the internal pore area can be effectively used. At the same time, the operation can be performed without liquid permeation resistance, and at the same time, many ligands can be easily and stably immobilized.

【Example】

[0026]

Example 1 High density polyethylene (density 0.968, M
I value 5.5, trade name Hyzex 2208J), using a circular spinner having a spinner diameter of 10 mm, spinning temperature 150 ° C., polyethylene discharge 8 g / min, spinning distance 5 m, spinning cooling temperature 25 ° C., winding tension 3 gf , Winding speed 260m /
Minutes, melt spinning. The draft ratio at this time is 7,000
Met. After spinning, annealing was performed 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 stretching ratio at this time was about 1.3 times. Next, at three successive temperatures of 108 ° C., 119 ° C. and 122 ° C., the respective roller speeds are 6 m / min and 7.8.
The film was stretched and opened by hot stretching at a stretching speed of 8.7 m / min at 8.7 m / min to obtain a porous support made of polyethylene having a solid fiber membrane-like porous structure. The total stretching 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 an ethylene / vinyl alcohol copolymer having an ethylene content of 30 mol% to an aqueous ethanol solution for 1.0%.
It was immersed in a solution in which the weight percentage was dissolved to obtain a coated carrier having a hydrophilic coating layer of an ethylene / vinyl alcohol copolymer. The coated carrier has an average pore size of 0.42 μm by a mercury intrusion method, a total pore volume of 4.4 ml / g, a porosity of 80.0%, and a total surface area of 2
The volume of pores having a diameter of 9.1 m ² / g and a pore size of 0.01 μm or more and 10 μm or less was 93% of the total pore volume. Next, the coated carrier (cut to a length of 10 cm, 800 pieces) is mixed with 40 ml of a mixture of 5 volumes of dimethyl sulfoxide, 4 volumes of epichlorohydrin, and 1 volume of 10 N aqueous sodium hydroxide solution.
The mixture was reacted at 2 ° C. for 2 hours to introduce an epoxy group. Phenylalanine was reacted with the coated carrier having the epoxy group introduced therein in a 0.1N aqueous sodium hydroxide solution to obtain a phenylalanine-fixed adsorbent. The fixed amount of phenylalanine was 71 μ equivalent per 1 ml of the adsorbent. The phenylalanine-fixed adsorbent has an average pore size of 0.22 μm by mercury intrusion method,
Total pore volume 3.9 ml / g, total surface area 66.1 m ² /
g, the amount of the coating layer determined from the weight change before and after the immersion treatment was 3.0 × 10 ⁻³ g / m ² . The non-specific adsorption was measured using a 10 cm long phenylalanine-fixed adsorbent 200
Immerse the book in 6 ml of rheumatic patient plasma and shake
The reaction was performed at 7 ° C. for 2 hours. Rheumatoid factor is R
It was measured by the A test method. The rate of decrease in 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,
The respective adsorption rates of fibrinogen, calcium ion and chloride ion are 50.0%, 2.6%, 9.1%,
4.2%, 1.7%, 8.8%, 0.3%, and 0%, exhibit high adsorption to rheumatoid factor as an adsorption target substance, and are nonspecific for other plasma components No adsorption was seen.

[0027]

Example 2 High density polyethylene (density 0.968, M
I value 5.5, trade name HIZEXX 2208J) using a circular spinner having a spinner diameter of 35 mm, spinning temperature 150 ° C., polyethylene discharge amount 16 g / min, spinning distance 5 m, spinning cooling temperature 24 ° C., winding tension 10 gf , Winding speed 400
m / min. The draft ratio at this time is 24,
000. After spinning, annealing was performed at 115 ° C. for 2 hours. At room temperature (24 ° C), the obtained polyethylene yarn is
Primary roller speed 3.75 m / min, secondary roller speed 5
Cold stretching was performed at m / min. The cold stretching ratio at this time was about 1.3 times. Then continuously 108 ° C, 119 ° C, 122 ° C
Roller speed of 15m /
, 19.5 m / min and 21.8 m / min, and stretched and opened to obtain a polyethylene porous support having a solid fiber membrane-like porous structure. The total stretching 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 in which polyhydroxyethyl methacrylate (molecular weight: about 50,000) was dissolved at 1.0% by weight in an aqueous methanol solution to obtain a coated carrier having a polyhydroxyethyl methacrylate hydrophilic coating layer. . 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 (length: 10 cm, 100 pieces) is immersed in a solution of diethylamine dissolved in a 10% aqueous ethanol solution to a concentration of 30%,
Irradiated with 25 kGy of gamma rays. After the irradiation, the resultant was sufficiently 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 a mercury intrusion method. The pore volume was 88% of the total pore volume. Example 1
Non-specific adsorption was measured using plasma of a patient with hepatic failure in the same manner as described above. Total bilirubin, albumin, Ig
G, transferrin, total cholesterol, fibrinogen, calcium ion, and chloride ion adsorption rates were 62.4%, 3.1%, 3.3%, 5.5%, respectively.
0.3%, 4.7%, 0.1%, and 06%, showing high adsorptivity to total bilirubin as the target substance for adsorption,
In addition, nonspecific adsorption of other plasma components was not observed.

[0028]

Example 3 700 adsorbents of Example 1 (filling rate 35
%) Was inserted into a cylindrical container made of polycarbonate having an inner diameter of 8 mm and a length of 10 cm, in which the adsorbents were arranged in the longitudinal direction of the container, and both ends of the adsorbent were adhered and fixed together with the container with urethane. At this time, both ends of the container were sealed with urethane. The container had a separate entrance and exit on the side. The entrance and the exit were not blocked by urethane at both ends, and were provided at positions farthest from each other. An adsorber was obtained as described above. Next, direct perfusion of blood was evaluated using the obtained adsorber. Blood from a healthy subject was collected in the presence of ACD-A1 / 9 volume as an anticoagulant. 40 ml of this blood was placed in the adsorber for 1.
Perfusion was performed at 2 ml / min, and the platelet count in the adsorber effluent was measured. The platelet reduction rate was extremely small at 9.7%, indicating excellent platelet permeability.

──────────────────────────────────────────────────続 き Continued on front page (58) Field surveyed (Int.Cl. ⁷ , DB name) B01J 20/00-20/34

Claims (9)

(57) [Claims] It is to 1. A surface of the actual fiber 維状 porous carrier in the adsorbent for made of an organic synthetic polymer material having a polymer coating layer
A coated carrier, wherein the pore shape of the solid fibrous porous carrier is
A coated carrier characterized by being a through hole . 2. The coated carrier according to claim 1, wherein the polymer coating layer is a hydrophilic synthetic compound having a hydroxyl group. 3. The amount of the polymer coating layer is 10 ⁻⁵ g / m ^2.
The coated carrier according to claim ^2, which is not less than 1 g / m2. 4. The coated carrier according to claim 1, wherein the ligand substance is insolubilized by covalently bonding to the hydrophilic coating layer. 5. The coated carrier according to claim 1, which is for an adsorbent made of an organic synthetic polymer material and has fine pores having an average pore size of 0.01 μm or more and 10 μm or less. 6. The total surface area is 1 m ² / g or more and 500 m ^2.
2 / g or less. 7. The coated carrier according to claim 1, wherein the volume of pores having a pore size 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, comprising a polyolefin. 9. Pore shape made of organic synthetic polymer material
Hydroxy is added to the surface of the solid fibrous porous carrier that is a through hole.
A hydrophilic polymer coating layer having a sil group;
Coating in which the ligand substance is covalently insolubilized in the covering layer
The carrier is filled into the container in the form of a fiber bundle and is fixed to the container.
An adsorption column for extracorporeal circulation treatment, characterized in that it is used.