JPS5812656A - Adsorbing material for treating recirculation - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an adsorbent for extracorporeal circulation therapy in which a particulate carrier holds a ligand capable of binding to an adsorbed substance. More specifically, diseases and phenomena related to biological immune function such as fleas, immunoproliferative syndrome, rheumatoid arthritis, systemic lupus erythematosus, allergies, rejection reactions during organ transplants, kidney diseases such as nephritis, hepatitis, etc. The present invention relates to an adsorbent that adsorbs and removes malignant substances from body fluids, such as blood and plasma, which are thought to be closely related to the cause or progression of diseases, such as liver disease.

Conventionally, activated carbon or activated carbon coated with a hydrophilic polymer has been used as an artificial liver for liver diseases, mainly for extracorporeal circulation therapy. However, as mentioned above, in many diseases, various malignant substances that are closely related to the cause or progression of the disease have become known, and there is a need to selectively remove these malignant substances from body fluids. However, activated carbon-based adsorbents have low adsorption and resistance properties, and the current state of the art is unparalleled.

In order to respond to the demand for selective adsorption and removal of malignant substances, the present inventors have conducted extensive research and have developed a special substance that has a biological and/or chemical selective interaction with the adsorbed substance on the carrier. He discovered various adsorbents that hold chemical bonds and filed a patent application. (Special application 1281-1981)
83.128184.56-7152.18923.4
1700) Furthermore, the present inventors conducted detailed research on particulate carriers used in the adsorbent, particularly particulate carriers for extracorporeally circulating oil.

Hitherto, no carrier specifically designed for this purpose is known. Therefore, there was no choice but to repurpose a carrier that is generally known for use in affinity chromatography.

Known carriers include natural polymer roses such as agarose-based carriers, dextran-based carriers, and cellulose-based carriers (Pharmacia, Sweden). However, these natural polymer carriers have the following drawbacks.

(1) There are many operational restrictions due to insufficient mechanical strength. For example, the carrier may be destroyed during preparation of the adsorbent such as activation or immobilization, or the carrier may break or crumble during transportation or use.

(2) Since it is a soft gel, when it is packed into a column and used for extracorporeal circulation, body fluid containing the substance to be removed cannot be passed through at a high flow rate. When a high viscosity, high solute concentration liquid such as a body fluid is flowed at a high flow rate, since it is a soft gel, the filling volume decreases, causing clogging and a decrease in flow rate, which may eventually stop flowing.

(3) Since it is a soft gel and does not have permanent bores, it cannot be easily sterilized, which is an essential requirement for an adsorbent for extracorporeal circulation therapy. For example, in the case of chemical sterilization such as ethylene oxide gas sterilization, the material is sterilized by freeze-drying, but the pores are destroyed by the freeze-drying and will not return to their original state even if they are re-dispersed in an aqueous medium. During freeze-drying, its volume decreases to about half, and even when it is redispersed in an aqueous medium, it only returns to about 80% of its original volume, and its adsorption capacity usually decreases. There is a method of mixing additives to protect the pores during freeze-drying, but to prevent the additives from entering body fluids, thorough cleaning must be performed before use.

Furthermore, heat sterilization such as high-pressure steam sterilization cannot be used because it destroys the pores. Similarly, radiation sterilization cannot be used as it destroys the skeleton and pores.

(4) Furthermore, when natural polymeric carriers are used for extracorporeal circulation therapy, they are said to cause activation of the complement system and coagulation system, resulting in leucovenia, thrombocyte venia, etc., and are therefore undesirable.

The present inventors have completed the present invention as a result of intensive research into a carrier for extracorporeal circulation therapy that overcomes the drawbacks of conventional carriers.

That is, the present invention provides an extracorporeal circulation 5-therapeutic adsorbent comprising a particulate carrier holding a ligand capable of binding to an adsorbed substance, which comprises a hard gel carrier in which the particulate carrier has a specific surface area of at least 5 V. The present invention relates to an adsorbent for extracorporeal circulation therapy.

The hard gel carrier is a crosslinked synthetic polymer having hydroxyl groups,
Average particle size is 25-2500μm1 Water retention capacity is 0.6-6
When the g force and hydroxyl group density are in the range of 5 to 17 meq/9, it becomes a more preferable adsorbent for extracorporeal circulation treatment. Furthermore, the hard gel carrier is a crosslinked synthetic polymer mainly composed of vinyl alcohol units, which is obtained by hydrolyzing a copolymer of a vinyl ester of acyl or carboxylic acid and a vinyl compound having an isocyanurate ring. The adsorbent for extracorporeal circulation therapy is particularly preferred.

The carrier used for this purpose has physical properties (1
) Mechanical strength sufficient to withstand adjustment, transportation, use, etc. of the adsorbent such as activation and immobilization;
Hardness and average particle size that allow high solute concentration and high viscosity body fluids such as blood to flow at high flow rates, (3) Chemical sterilization such as ethylene oxide gas sterilization (freeze-drying sterilization), and heat sterilization such as high-pressure steam sterilization. Physical stability of the pores to withstand sterilization is required. The present inventors have investigated various existing carriers and newly synthesized carriers with different physical properties, and have surprisingly found that the hard gel carrier satisfies the above requirements, especially for certain It has been found that carriers with characteristic values give favorable results.

In the present invention, a hard gel refers to a gel whose physical property values maintain a certain value or more when an external force is applied. Specifically, when gel is filled into a container with a diameter of 10 fins and a length of 50 fins and water is passed through it, the volume reduction rate of the gel is 10% or less when the pressure difference between the inlet and outlet of the container is 200 Hg. refers to something that is. Further, when such a gel is freeze-dried, its specific surface area maintains a value of 5 mV9 or more.

The specific surface area is expressed as the surface area occupied by nitrogen gas adsorbed per unit weight of dry gel. −′)
The specific surface area indicates how effectively the substance constituting the gel per unit weight forms a surface in a dry state.

Generally, polymer gels swell in a medium that has an affinity for the gel and shrink when dried. In the case of a soft gel in which the medium-filled bores are maintained only by cross-linked networks during swelling, the networks collapse upon drying, and most of the bores disappear.

In this case, the specific surface area generally shows a low value of 1φ or less because it is a value only for the outside of the particle. Since the agarose conventionally known for use in affinitai chromatography is a soft gel, its bores disappear when it dries. Therefore, it is not easy to desteminate it, and furthermore, it has a soft mesh that is easily crushed, so even when it is packed into a column and used for extracorporeal circulation, body fluids cannot be passed through it at a high flow rate for a long time.

On the other hand, in the case of a hard gel whose bores have a rigid structure and can withstand freeze-drying and heat sterilization, the bores will shrink somewhat when dried, but will maintain most of their swollen state. In other words, it has permanent bores and a specific surface area that is higher than that of a soft gel, at least 5 or more.

The hard gel used as the carrier of the present invention has a specific surface area of at least 50 or more, and generally the larger the value, the better. The upper limit can be used up to 1000 d/9th place.

There are various methods for measuring the specific surface area, but in the present invention, it was determined by the most common BET method using nitrogen gas. In addition, the sample used for specific surface area measurement must be sufficiently dried, but the carrier of the present invention is difficult to dry, so after equilibrating the water-wetted carrier with A7T, the sample should be kept at 60"C or lower. The sample was dried under reduced pressure and used as a sample for measurement.

The water retention capacity (hereinafter referred to as WR) of the hard gel used in the present invention is suitably in the range of 0.5 to 169/9, and most preferably in the range of 1.0 to 5.09A. Give results.

wR is the amount of physiological saline that the gel can contain within the particles when the gel is equilibrated with physiological saline, expressed as a value per dry weight of gel. In other words, WRl is a measure of pitting corrosion within the gel. As wR increases, the weight of the part forming the skeleton per unit volume of the gel in water, that is, the weight of the gel itself 9- and the mechanical strength of the gel in physiological saline and even body fluids decreases relatively. Furthermore, if WR becomes too small, pitting corrosion per unit weight (or unit volume) effective for adsorption will decrease, resulting in a decrease in adsorption capacity. Therefore, it is preferable for the carrier for this purpose that WR be within an appropriate range.

WR9 measures the weight (total) of a sufficiently dried gel in advance, and then centrifuges the gel, which has been sufficiently equilibrated with physiological saline, to remove the physiological saline attached to the gel surface, and then calculates the weight IW. , ) can be determined by the following formula.

■ As mentioned above, it is preferable that the water retention amount of the hard gel carrier used in the adsorbent of the present invention falls within a certain range;
In order to maintain effective adsorption capacity and to stably flow liquids with high viscosity and high solute density, such as blood and plasma, at high flow rates for long periods of time, the average particle diameter of the hard gel carrier (
Dv) is preferably within a certain range.

- The smaller the average particle diameter, the higher the adsorption capacity, which is preferable, but if it is too small, body fluids cannot be stably distributed at a high flow rate for a long period of time. Therefore, the average particle size is 25-25
00 μm is preferable, and especially when used for whole blood, it is more preferably 150 to 1500 μm.

The exclusion limit molecular weight (Mtim) of a hard gel carrier used as an adsorbent for extracorporeal circulation therapy may be set by taking into consideration the molecular weight of the substance to be held by the hard gel carrier through chemical bonding and the molecular weight of the target adsorbed substance. Normal protein ML1m is 1
It ranges from 0" to 10".

Protein 'baitim' is a value indicating the lower limit of the molecular weight of molecules that cannot penetrate into the bores of the gel. MLim can be measured by a known method by filling a gel into a column and using a standard protein with a known molecular weight.

The chemical properties of the hard gel carrier used in the present invention include (
1) The density of functional groups is high so that substances (ligands) that can exhibit biological and/or chemical interactions with the adsorbed substance and can bind to it can be chemically bonded at a high density; (2) ) The carrier has little non-specific adsorption to plasma proteins, etc. so that it selectively adsorbs the target substance, (3) It has little reaction with biological components such as activation of the complement system and coagulation system, ( 4) Furthermore, when used as an adsorbent for whole blood, it is preferable to have properties such as interaction with blood cell components, ie, low thrombus formation, non-specific adhesion of blood cell components, residual blood, etc. Therefore, a carrier that satisfies the above chemical properties in addition to the physical properties already described is more preferably used.

As a result of intensive research, the present inventors have discovered that a hard gel carrier made of a crosslinked synthetic polymer having hydroxyl groups exhibits the above characteristics well. Furthermore, the hydroxyl group density is 5 to 1
Those in the range of 7 meq/9 gave preferable results, and especially those in the range of 6 to 15 m@q/9 gave more preferable results.

Generally, crosslinked synthetic polymers are composed of a linear polymer and a crosslinking agent, and are expressed in a hydroxyl base linear polymer. Therefore, a higher density of hydroxyl groups is preferable because it increases hydrophilicity, reduces interaction with biological components, and improves ligand retention capacity, but if it is too high, the crosslinking agent content decreases and the strength of the carrier decreases. descend. Furthermore, if the density of hydroxyl groups is too low, non-specific adsorption will occur, which is not preferable.

The density of hydroxyl groups can be determined by reacting the gel with acetic anhydride in a pyridine solvent and measuring the amount of acetic anhydride consumed by the reaction with the hydroxyl groups or the change in weight of the gel. The hydroxyl group density when the dried gel 19 reacts with 1 mmoL of acetic anhydride is 1 meq/9.

A hydrophilic crosslinked synthetic polymer having a hydroxyl group can be synthesized by polymerizing a heptadmer having a hydroxyl group or introducing a hydroxyl group through a chemical reaction of the polymer. It is also possible to synthesize both in combination. As the polymerization method, a radical polymerization method can be used. The crosslinking agent is preferably introduced by copolymerization during polymerization. In addition, introduction through a chemical reaction of polymers (between polymers, between polymers and a crosslinking agent) may be used in combination.

- For example, it can be made by copolymerizing a vinyl monomer with a vinyl or allyl crosslinking agent. Examples of the hydrophilic crosslinked synthetic polymer in this case include crosslinked vinyl polymers such as crosslinked polyvinyl alcohol, crosslinked poly2-hydroxyethyl acrylate, and crosslinked poly2-hydroxyethyl methacrylate. A crosslinked synthetic polymer containing vinyl alcohol units as a main component in the amount of 2-crosslinked vinyl alcohol can provide a high hydroxyl group density and give preferable results.

Examples of crosslinking agents include allyl compounds such as triallyl isocyanurate and triallyl cyanurate, di(meth)acrylates such as ethylene glycol dimethacrylate and diethylene glycol dimethacrylate, butanediol divinyl ether, diethylene glycol divinyl ether, and tetravinyl. Polyvinyl ethers such as glyoxal, polyallyl ethers such as diarylidene pentaerythritol and tetraallyloxyethane, and glycidyl acrylates such as glycidyl methacrylate can be used. In particular, triallylisocyanurate units are preferred from the viewpoints of mechanical strength, hardness, micropore structure, and chemical properties.

If necessary, copolymerized comonomers such as vinyl esters and vinyl ethers may also be used.

In the case of vinyl copolymers, triallyl of polyvinyl alcohol obtained by copolymerizing a vinyl ester of carboxylic acid and a vinyl compound (allyl compound) having an isocyanurate ring, and cross-degrading the copolymer. Isocyanurate crosslinkers provide particularly good supports in terms of mechanical strength, hardness, pore stability and chemical properties.

Methods for attaching the ligand to the rigid gel support include covalent bonding,
Any known method such as ionic bonding, physical adsorption, embedding, or precipitation and insolubilization on the surface of a polymer can be used, but in view of the elution properties of the bound substance, it is preferable to fix and insolubilize by covalent bonding. Therefore, it is possible to use commonly known methods for activating immobilized enzymes, carriers used in affinity chromatography, and binding methods for ligands.

Examples of activation methods include cyanogen halide method, epichlorohydrin method, bisepoxide method, cyanogen halide method, bromoacetyl bromide method, ethyl chloroformate method, 1,1'-carbonyldiimidazole method, etc. can. The activation method of the present invention is not limited to the above examples as long as it can perform a substitution and/or addition reaction with a nucleophilic reactive group having active hydrogen such as an amino group, a hydroxyl group, a carboxyl group, or a thiol group of the ligand. .

In the present invention, the ligands to be retained on the hard gel carrier will be exemplified.

For the treatment of systemic lupus erythematosus, homopolymers of mono-, di-, and trinucleotides such as adenine, guanine, cytosine, uracil, and thymine, or fuvolimer, and naturally occurring DNA5RNA for adsorption and removal of anti-nuclear antibodies and anti-DNA antibodies. Nucleic acids such as can be used. Also, for adsorption and removal of DNA, RNA, and ENA present in the blood.
Anti-nucleic acid antibodies such as anti-single-stranded DNA antibodies, anti-double-stranded DNA antibodies, anti-RNA antibodies, and anti-ENA antibodies, and basic compounds such as methylated albumin actinomycin D can be used. Furthermore, for the adsorption and removal of immune complexes in the blood, C1
Antibodies against immune complexes such as complement components such as q, specific proteins such as protein A, and anti-heavy chain constant region second phase antibodies can be used.

For the treatment of rheumatoid arthritis and malignant rheumatoid arthritis,
Modified γ-globulins modified by chemical modification (coagulation) methods such as urea, guanidine hydrochloride, mercaptoethanol, surfactants, organic solvents, etc., physical modification (coagulation) methods such as heat, ultrasound, gas bubbling, etc. Antigen-like substances against rheumatoid factor, such as immunoglobulin, aggregated T-globulin, aggregated immunoglobulin, Fc region of immunoglobulin, heavy chain constant phase 2 of immunoglobulin, and modified products thereof by the above-mentioned modification method, and anti-rheumatoid factor. It can be done using antibodies.

In addition, for the removal of immune complexes from rheumatism, antibodies against immune complexes such as complement components such as C1q, specific proteins such as protein A, and anti-heavy chain constant region second phase antibodies can be used.

Microsomal fractions of volvulus, thyroglobulin, and thyroid gland can be used for the treatment of Hashimoto's disease.

For the treatment of myasthenia gravis, neuromuscular acetylcholine receptor fraction components can be used.

Glomerular basement membrane components for the treatment of glomerulonephritis, platelet membrane components and platelet granule fraction components for the treatment of idiopathic thrombocytopenic purpura, and transcortisin and anti-cortiscin antibodies for the treatment of Cushing syndrome. Can be used.

For the prevention and treatment of hepatitis, antibodies against surface antigens of viruses such as hepatitis A virus and hepatitis B virus can be used.

Anti-angiotensin 1 antibodies can be used to treat hypertension, and heparin and anti-riboprotein antibodies can be used to treat hyperlipidemia.

For treatment of immune diseases based on lymphocyte abnormalities, anti-lymphocyte antibodies such as anti-B cell antibodies, anti-pressor T antibodies, and anti-lymphocyte antibodies can be used.

Protein A1 anti-immunoglobulin antibodies can be used to treat cancer such as breast cancer.

Ligands that can be used in the present invention are not limited to the above examples, but include lectins such as congnitinin, concanavalin A, and phytohemaagglutinin, nucleic acids,
amino acids, lipids, protamine, heparin, antigens, antibodies,
Known substances capable of binding to the a-layer covering substance, such as enzymes, substrates, and coenzymes, can be used.

It is also possible to use a hard gel carrier holding two or more types of ligands. Furthermore, two or more types of carriers holding ligands can be used in combination.

As described above, the adsorbent for extracorporeal circulation treatment of the present invention has sufficient mechanical strength, so it does not cause destruction, chipping, etc. during the preparation and transportation of the adsorbent such as activation and immobilization, especially when used in extracorporeal circulation. There is virtually no formation of mold, and a wide range of operating methods and conditions can be selected. In addition, since it is a hard gel, when it is packed into a column and used for extracorporeal circulation, body fluids containing substances to be adsorbed and removed can be stably passed continuously at a high flow rate for a long period of time. Furthermore, since it is a hard gel and has permanent bores, it can be easily sterilized, which is an essential requirement for an adsorbent for extracorporeal circulation therapy. For example, chemical sterilization such as ethylene oxide gas sterilization by freeze-drying the adsorbent can also be carried out without impairing the adsorption capacity of the adsorbent. It has the advantage of being able to be implemented while maintaining high levels of ability without sacrificing ability.

Furthermore, the particulate hard gel carrier made of a hydrophilic crosslinked synthetic polymer having hydroxyl groups had favorable chemical properties in addition to the above-mentioned physical properties, and exhibited the following effects.

Because it has a high hydroxyl group density, it is possible to chemically bond ligands at a high density, resulting in a high adsorption capacity for the target substance.
Because it is highly hydrophilic, there is little non-specific adsorption to plasma proteins, etc. In addition, there is little reaction with biological components such as activation of the complement system and coagulation system, and furthermore, when used as an adsorbent for whole blood, there is no interaction with blood cell components, such as thrombus formation and non-specific adhesion of blood cell components. , there is little residual blood, etc., and it can be used suitably.

The adsorbent of the present invention can be applied to general uses for purifying and regenerating body fluids such as autologous plasma and autologous blood, and can be used to treat collagen diseases such as cancer, immunoproliferative syndrome, rheumatoid arthritis, systemic lupus erythematosus, and severe Effectively used for extracorporeal circulation treatment of autoimmune diseases such as myasthenia, allergies, diseases and phenomena related to the body's immune function such as rejection reactions during organ transplants, kidney diseases such as nephritis, liver diseases such as hepatitis, etc. can.

Embodiments of the present invention will be explained in more detail with reference to Examples below.

Example 1 100 g of vinyl acetate, ) realyl isocyanurate) 2
4.19 (X=0.20), ethyl acetate 124,
Heptane 124g, polyvinyl acetate (polymerization degree 5oo) 3
, 1g and 2,2'-azobisisobutyronitrile 3
．． A homogeneous mixture consisting of 1g and 1g of polyvinyl alcohol
% by weight, 0.05% by weight of sodium dihydrogen phosphate 21-dihydrate and dihydrogen phosphate (IJ)
400% of water in which 165% by weight of um-dihydrate was dissolved was placed in a flask, stirred thoroughly, and heated to 18% by weight at 56.5°C.
Suspension polymerization was carried out by heating and stirring at 75° C. for 5 hours to obtain a granular copolymer. After filtering, washing with water, and then extracting with acetone, 46.59% of caustic soda and 2% of methanol were added.
The transesterification reaction of the copolymer was carried out at 40''C for 18 hours in a solution consisting of t.

The average particle size of the obtained particles was 150 μm.

When the hydroxyl group density (qOH) was determined using the above method, it was 13m.
It was eq/9. The water retention capacity of the gel was 4.4979 dry gel, and the specific surface area was 10 T11'/9. Furthermore, the exclusion limit molecular weight of the gel was measured using a phosphate buffered saline solution of a standard globular protein, and was found to be approximately 1.8 million.

Next, gel 5 was transesterified and thoroughly washed with water.
Suspend 0 cc in 200 sd of water, add 3 g of cyanogen bromide, and stir using a propeller stirring blade. The pH was maintained at 10 to 11 using a 2N aqueous sodium hydroxide solution, and the reaction was carried out for 8 minutes. After the reaction was completed, it was immediately filtered through a glass filter, and then washed with 2 tons of water to obtain an activated gel.

Furthermore, the activated gel 5- is washed with 0.1 M sodium bicarbonate 50-. Protein A30W as a ligand
19 is dissolved in 0.1 M sodium bicarbonate, the pH is adjusted to 9.5 using an aqueous solution of caustic soda, and the mixture is added to the activated gel. This was then shaken at 25"C for 16 hours.
Filter using a glass filter.

The obtained adsorbent was mixed with 0.1M sodium bicarbonate solution and acetate buffer (P)I4. Washed alternately with O'l.

When the adsorbent was compared with the original gel particles and observed under an optical microscope, no breakage such as chipping or flaking was observed.

This adsorbent was packed into a 4-column (L/D = 5), and human plasma was 0.2 m4/&+ and human whole blood (heparin added 1200 U/100-blood) was 0.5 f4/.
The solution was passed for 1 hour each using a single pass method. In all cases, no decrease in packing volume, clogging, or decrease in flow rate was observed, and the change in the pressure gauge in front of the column was 10 to 20 ssHg.

When we examined changes in plasma proteins and blood cell components before and after fluid passage, we found that albumin in plasma had only a slight change, and complements such as C3 and C4 had little decrease. about 30
% adsorbed. In whole blood, the column was only pale red in color, and there was very little residual blood. When the surface of the adsorbent was observed using an optical microscope, there were few red and white blood clots. In addition, when the number of blood cells on the column passing surface was counted, there was a relatively small decrease in red blood cells, platelets, and white blood cells.

Example 2 Using the polymerization method and saponification method shown in Example 1, a gel with the physical properties shown in the table below was obtained. After the gel was activated and fixed in the same manner as in Example 1, When the adsorbent was compared with each of the original gel particles and observed under an optical microscope, no damage such as chipping or flaking was observed.

In addition, when human plasma and human whole blood (heparin-added 1200U/100 + wj blood) were passed through in the same manner as in Example 1, there was almost no decrease in filling volume, clogging, or decrease in flow rate for any of the adsorbents. When we investigated changes in plasma proteins, we found that the decrease in complements such as albumin and C4 was minimal. Adsorption of globulin by immobilized protein A was observed in all cases,
Approximately 1525- ~50% reduction.

Even in experiments using whole blood, there were relatively few residual blood, thrombus formation, and blood cell count changes.

Example 3 Vinyl acetate 1009, triallyl isocyanurate 32
．． 29 (X=0.25), ethyl acetate 1009, n
- A homogeneous mixture of 100 g of heptatool, 6.6 g of polyvinyl acetate and 3.3 g of 2,2'-azobisisobutyronitrile was subjected to suspension polymerization in the same manner as in Example 1, and the resulting particles were transesterified. A reaction was carried out. The physical properties of the obtained gel are as follows: average particle size: 100 μm 1qOH = 12meq/9
, WR=3.49/9 and specific surface area is 20t
It was l/9.

The exclusion limit molecular weight was measured in the same manner as in Example 1 and was approximately 2.
It was 0,000,000. Activation was performed in the same manner as in Example 1, and protamine was used instead of protein A for immobilization. The rest is the same as in Example 1. Wet adsorbent at 121”Cl
When sterilized in an autoclave for 20 minutes, almost no volume reduction of the adsorbent was observed. When human plasma was passed through two types of adsorbents, sterilized and unsterilized, in the same manner as in Example 1, the decrease in complements such as albumin, Cq, and C4 was minimal.
The adsorption of was measured by simple immunodiffusion method and was found to be significant in both cases, with a decrease of about 35%.

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Claims (1)

[Claims] 1. An adsorbent for extracorporeal circulation therapy in which a particulate carrier holds a ligand capable of binding to an adsorbed substance, which comprises a hard gel carrier in which the specific surface area of the core particulate carrier is at least 5. An adsorbent for extracorporeal circulation therapy. 2. The hard gel carrier is a crosslinked synthetic polymer having hydroxyl groups, and the average particle size is 25 to 2500 μm1, and the water retention capacity is 0.5
The adsorbent for extracorporeal circulation treatment according to claim 1, having a hydroxyl group density of 5 to 17 meq/9. 3. The adsorbent for extracorporeal circulation treatment according to claim 1 or 2, wherein the hard gel carrier is a crosslinked synthetic polymer whose main constituent is vinyl alcohol units. 4. Any one of claims 1 to 3, wherein the hard gel carrier is a crosslinked synthetic polymer obtained by hydrolyzing a copolymer of a vinyl compound of carboxylic acid and a vinyl compound having an isocyanurate ring. The adsorbent for extracorporeal circulation treatment described in .