JPH0323182B2 - - Google Patents

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 the body's immune system such as cancer, 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 those associated with liver diseases. 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 growing need to selectively remove these malignant substances from body fluids. However, adsorbents based on activated carbon have low adsorption selectivity and cannot currently meet this demand. 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. We have discovered various adsorbents that are held together by chemical bonds, and have previously applied for a patent. (JP-A-57-122875, JP-A-57-
134164, JP-A-57-156035) Furthermore, the present inventors conducted detailed research on particulate carriers used in the adsorbent, particularly particulate carriers for extracorporeal circulation treatment. 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. As known carriers, natural polymer carriers such as agarose-based carriers, dextran-based carriers, and cellulose-based carriers are known (for example, trade name: Cepharose, 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 adsorbent may be destroyed during the preparation of the adsorbent during activation or immobilization, or the carrier may break during transportation or use.
Kudake occurs. (2) Since it is a soft gel, when it is packed into a column and used for extracorporeal circulation, it is not possible to flow body fluids containing substances to be removed at a high flow rate. When a high viscosity, high solute concentration liquid such as 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 pores, it cannot be easily sterilized, which is an essential requirement for adsorbents for extracorporeal circulation therapy. For example, in the case of ethylene oxide gas sterilization or chemical sterilization, sterilization is performed by freeze-drying, but the pores are destroyed by freeze-drying and do not return to their original state even if they are redispersed in an aqueous medium. During freeze-drying, its volume decreases to about half, and even when redispersed in an aqueous medium, it remains at most 80% of its original volume.
It usually returns only to a certain extent and the adsorption capacity also decreases. Some methods include adding additives to protect the pores during freeze-drying, but to prevent the additives from entering body fluids, they must be thoroughly washed 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 polymer carriers are used for extracorporeal circulation therapy, they are said to activate the complement system and coagulation system, resulting in leucopenia, thrombocytopenia, etc., and are therefore not very desirable. 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 adsorbent for extracorporeal circulation therapy in which a porous particulate carrier holds a ligand capable of binding to an adsorbed substance through a covalent bond, wherein the porous particulate carrier contains a hydrophilic crosslinked organic compound having a hydroxyl group. A carrier made of a synthetic polymer, having a water retention capacity of 0.5 to 6 g/g and a hydroxyl group density of 5 to 17 meq/g, the specific surface area of the carrier being at least 5 m ² /g, and the diameter of the carrier being When filling a container of 10 mm and length 50 mm and passing water through it, the pressure difference between the inlet and outlet of the container is
The present invention relates to an adsorbent for extracorporeal circulation therapy, which is a hard gel carrier with a volume reduction rate of 10% or less at 200 mmHg. In the above adsorbent,
When the average particle diameter of the hard gel carrier is in the range of 25 to 2500 μm, 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, and 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 therapy is particularly preferred. The carrier used for this purpose has physical properties such as (1) adjustment of adsorbent such as activation and immobilization, transportation,
Mechanical strength sufficient to withstand use, etc.; (2) hardness and average particle size that allow high solute concentration and high viscosity body fluids such as plasma and blood to flow at high flow rates when filled into columns;
(3) Physical stability of the pores is required to withstand chemical sterilization (lyophilization sterilization) such as ethylene oxide gas sterilization and heat sterilization such as high-pressure steam sterilization. As a result of studying various existing carriers and newly synthesized carriers with different physical properties, the present inventors found that
Indeed, it has been surprisingly found that hard gel carriers satisfactorily meet the above requirements, and in particular that carriers with certain characteristic values give favorable results. In the present invention, the term "hard gel carrier" refers to one that maintains gel physical property values above a certain value when external force is applied. Specifically, the gel is 10 mm in diameter and 50 mm in length.
When filling a container and passing water 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 mmHg. Furthermore, when such a gel is freeze-dried, its specific surface area is 5 m ² /
Hold a value greater than or equal to g. The specific surface area is expressed as the surface occupied by nitrogen gas adsorbed per unit weight of dry gel. In other words, the specific surface area indicates how effectively the substance constituting the gel per unit weight forms the 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 pores that are filled with the medium during swelling are maintained only by a network of crosslinks, when the gel dries, the network collapses and the pores almost disappear. In this case, the specific surface area is almost limited to the outside of the particle, so it generally shows a low value of 1 m ² /g or less. Since the agarose conventionally known for use in affixine chromatography is a soft gel, its pores disappear when it dries. Therefore, it is not easy to sterilize, and furthermore, it has a soft mesh that is easily crushed, so even when packed in a column and used for extracorporeal circulation, body fluids cannot be passed through it at a high flow rate for a long period of time. On the other hand, in the case of a hard gel that has a firm pore structure and can withstand freeze-drying and heat sterilization, the pores will shrink somewhat when dried, but will maintain most of their swollen state. In other words, it has permanent pores, and its specific surface area is higher than that of soft gel, and is at least 5 m ² /g. The hard gel used as the carrier of the present invention has a specific surface area of at least 5 m ² /g or more, and it is generally preferable that this value is as large as possible. The upper limit can be used up to about 1000m ² /g. 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 dry, but since the carrier of the present invention is difficult to dry, the carrier wet with water is equilibrated with acetone and then dried under reduced pressure at 60°C or less. This was used as a sample for measurement. The water retention capacity (hereinafter referred to as W _R ) of the hard gel used in the present invention is suitably in the range of 0.5 to 6 g/g, and preferably in the range of 1.0 to 5.0 g/g for best results. give. W _R is the amount of saline that the gel can contain within the particles when the gel is equilibrated with saline, expressed as a value per dry weight of gel. In other words, W _R is a measure of the amount of pores in the gel. As W _R 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, and the mechanical strength of the gel in physiological saline and even body fluids decrease relatively. Furthermore, if W _R becomes too small, the amount of pores 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 W _R be within an appropriate range. W _R measures the weight (W ₂ ) 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. The weight (W ₁ ) can be measured and calculated using the following formula. W _R = W ₁ - W ₂ /W ₂ (g/g) As mentioned above, in the hard gel carrier used for the adsorbent of the present invention, it is preferable that the water retention amount falls within a certain range, but the effective adsorption capacity In order to maintain stable flow of fluids with high viscosity and high solute concentration such as blood and plasma for long periods of time at high flow rates,
Furthermore, it is preferable that the average particle diameter (D _W ) of the hard gel carrier is 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 time. Therefore, the average particle diameter is preferably 25 to 2500 μm, more preferably 150 to 1500 μm, especially when used for whole blood.
It is. The exclusion limit molecular weight (Mim) 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 adsorbent.
It is usually in the range of 10 ³ to 10 ⁸ for the protein Mim. Protein Mim is a value indicating the lower limit of the molecular weight of molecules that cannot penetrate into the pores of the gel. M
im can be measured by a known method by filling a gel into a column and using a standard protein of known molecular weight. The chemical properties of the hard gel carrier used in the present invention include (1) a high density of substances (ligands) that exhibit, for example, biological and/or chemical interactions with the adsorbed substance and can bind to it; (2) The carrier has low nonspecific adsorption to plasma proteins, etc. so that it selectively adsorbs the target substance, (3) Complement system, coagulation system (4) Furthermore, when used as an adsorbent for whole blood, there is no interaction with blood cell components, such as thrombus formation, non-specific adhesion of blood cell components, and residual blood. It is preferable that the material has characteristics such as having a small number of problems. Therefore,
In addition to the physical properties already mentioned, a carrier that satisfies the above chemical properties is more preferably used. As a result of extensive 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, those with a hydroxyl group density in the range of 5 to 17 meq/g gave preferable results, and particularly those with a hydroxyl group density in the range of 6 to 15 meq/g gave more preferable results. Generally, crosslinked synthetic polymers are composed of a linear polymer and a crosslinking agent, and hydroxyl groups are expressed in the linear polymer. Therefore, the higher the density of hydroxyl groups, the more hydrophilic it becomes and the less interaction with biological components.
It is preferable because it also improves the retention capacity of the ligand, but if it is too high, the content of the crosslinking agent decreases and the strength of the carrier decreases. 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 reacting with the hydroxyl groups by measuring the change in weight of the gel. 1g of dry gel is 1mmo
The hydroxyl group density when reacting with acetic anhydride is
It is 1meq/g. A hydrophilic crosslinked synthetic polymer having a hydroxyl group can be synthesized by polymerizing a monomer having a hydroxyl group or introducing a hydroxyl group through a chemical reaction of a 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 and a vinyl or allyl crosslinking agent. In this case, the hydrophilic crosslinked synthetic polymers include crosslinked polyvinyl alcohol, crosslinked poly(2-
Hydroxyethyl acrylate, crosslinked poly2
- Crosslinked vinyl polymers such as hydroxyethyl methacrylate can be exemplified. In particular, crosslinked synthetic polymers containing vinyl alcohol units as a main component, such as crosslinked vinyl alcohol, can provide a high hydroxyl group density and give favorable results. Examples of crosslinking agents include allyl compounds such as triallyl isocyanurate and tolylyl 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 pentaerythrite 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, triallylisocyanurate crosslinking of polyvinyl alcohol obtained by copolymerizing a vinyl ester of carboxylic acid and a vinyl compound (allyl compound) having an isocyanurate ring and hydrolyzing the copolymer. The body provides a particularly good support in terms of mechanical strength, hardness, pore stability and chemical properties. Any known method such as covalent bonding, ionic bonding, physical adsorption, embedding, or precipitation insolubilization on the polymer surface can be used to bond the ligand to the hard gel carrier. It is preferable to use it after being fixed and insolubilized 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,
Examples include the halogenated triazine method, the bromoacetyl bromide method, the ethyl chloroformate method, and the 1,1'-carbonyldiimidazole method. 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, adenine,
Homopolymers or copolymers of mono-, di-, and trinucleotides such as guanine, cytosine, uracil, and thymil, and naturally occurring nucleic acids such as DNA and RNA can be used. also present in the blood
Anti-single-stranded for adsorption removal of DNA, RNA, and ENA.
DAN antibody, anti-double-stranded DNA antibody, anti-RNA antibody,
Anti-nucleic acid antibodies such as 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, complement components such as C1q, specific proteins such as protein A, anti-heavichain constant region 2
Antibodies to the immune complex, such as complementary antibodies, can be used. For the treatment of rheumatoid arthritis and malignant rheumatoid arthritis, chemical denaturation (coagulation) methods such as urea, guanidine hydrochloride, mercaptoethanol, surfactants, and organic solvents, physical denaturation (coagulation) methods such as heat, ultrasound, and gas bubbling are used. ) Modified γ modified by method
-Globulin, modified immunoglobulin, aggregated γ-
Antigen-like substances against rheumatoid factors such as globulin, aggregated immunoglobulin, Fc region of immunoglobulin, heavy chain constant region 2 of immunoglobulin, and modified products thereof by the above-mentioned modification method, and anti-rheumatoid factor antibodies can be used. . In addition, for the removal of rheumatoid immune complexes,
Antibodies against immune complexes such as complement components such as C1q, specific proteins such as protein A, and anti-heavichein constant region 2 phase antibodies can be used. For the treatment of Hashimoto's disease, thyglobulin, a microsomal fraction of thyroid gland, can be used. For the treatment of myasthenia gravis, neuromuscular acetylcholine receptor fraction components can be used. Glomerular basement membrane components are used to treat glomerulonephritis, platelet membrane components and platelet granule fraction components are used to treat idiopathic thrombocytopenic purpura, and transcortisone and anticortisone antibodies are used to treat Cushing syndrome. be able to. For the prevention and treatment of hepatitis, hepatitis A virus,
Antibodies against viral surface antigens such as hepatitis B virus can be used. Anti-angiotensin antibodies can be used to treat hypertension, and heparin and anti-lipoprotein antibodies can be used to treat hyperlipidemia. For the treatment of immune diseases based on lymphocyte abnormalities, anti-lymphocyte antibodies such as anti-B cell antibodies, anti-suppressor T antibodies, and anti-helper T antibodies can be used. Protein A and 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, promitan, heparin, antigens, antibodies, enzymes, Known substances that can bind to adsorbed substances such as 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 pores, it can be easily sterilized, which is an essential condition for an adsorbent for extracorporeal circulation therapy. For example, lyophilization of the adsorbent and chemical sterilization such as ethylene oxide gas sterilization can also be carried out without impairing the adsorption capacity of the adsorbent. The present invention has the advantage that the above-mentioned effects can be achieved without sacrificing the adsorption ability, which is a basic characteristic of the adsorbent, while maintaining high 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. Since it has a high hydroxyl group density, it can chemically bond ligands at a high density and obtain a high adsorption capacity for target substances, and because it is highly hydrophilic, there is little nonspecific adsorption to plasma proteins and the like. Also, the complement system,
There is little reaction with biological components such as activation of coagulated forms,
Furthermore, when used as an adsorbent for whole blood, there is little interaction with blood cell components, ie, thrombus formation, non-specific adhesion of blood cell components, residual blood, etc., and it can be suitably used. 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 is applicable to cancer, immunoproliferative syndrome, rheumatoid arthritis,
Collagen diseases such as systemic lupus erythematosus, autoimmune diseases such as myasthenia gravis, allergies, diseases and phenomena related to the body's immune function such as rejection during organ transplants, kidney diseases such as nephritis, and liver diseases such as hepatitis. It can be effectively used for extracorporeal circulation treatment such as. Embodiments of the present invention will be explained in more detail with reference to Examples below. Example 1 100 g of vinyl acetate, 24.1 g of triallylisocyanurate (X = 0.20), 124 g of ethyl acetate, 124 g of heptane, 3.1 g of polyvinyl acetate (degree of polymerization 500) and 3.1 g of 2,2'-azobisisobutyronitrile
A homogeneous mixed liquid consisting of polyvinyl alcohol 1
wt%, sodium dihydrogen phosphate dihydrate 0.05 wt% and disodium hydrogen phosphate dodecahydrate
Add 400ml of water in which 1.5% by weight was dissolved into a flask, stir thoroughly, and then heat at 56.5℃ for 18 hours.
Suspension polymerization was carried out by heating and stirring at 75°C for 5 hours.
A granular copolymer was obtained. After washing with water and then extracting with acetone, add 46.5 g of caustic soda and 2 methanol.
The transesterification reaction of the copolymer was carried out at 40°C for 18 hours in a solution consisting of: 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 13meq/g. Also, the water retention capacity of the gel is 4.4
g/g dry gel, and the specific surface area was 10 m ² /g. 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, 50 c.c. of the gel that has been transesterified and thoroughly washed with water is suspended in 200 ml of water, 3 g of cyanogen bromide is added, and the suspension is stirred using a propeller stirring blade. Adjust the pH to 10 using 2N sodium hydroxide solution
11 and allowed to react for 8 minutes. After the reaction was completed, it was immediately filtered through a glass filter and then washed with 2 portions of water to obtain an activated gel. Further, 5 ml of activated gel is washed with 50 ml of 0.1M sodium bicarbonate. Protein as a ligand
Dissolve 50 mg of A in 0.1 M sodium bicarbonate, adjust the pH to 9.5 using aqueous caustic soda solution, and add to the activated gel. This is then shaken for 16 hours at 25°C and filtered through a glass filter. The obtained adsorbent was washed alternately with 0.1M sodium hydrogen carbonate solution and acetic acid buffer (PH4.0). 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 ml column (L/D = 5), and human plasma was added at 0.2 ml/mm and human whole blood (heparin added 1200 U/100 ml blood) was added at 0.5 ml/mm using a single pass method. The solution was passed for an hour. 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 mmHg. When we examined changes in plasma proteins and blood cell components before and after fluid passage, we found that albumin in plasma showed only slight changes, and complements such as C ₃ and C ₄ decreased little; however, the interaction between protein A and globulin Approximately 30% of globulin was absorbed by the action. With 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 under an optical microscope, there were few red thrombi and white thrombi. Furthermore, when the number of blood cells in the blood passing through the column 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 having the physical properties shown in the table below was obtained.

[Table] After activating and fixing the gel in the same manner as in Example 1, the adsorbent was compared with the original gel particles and observed under an optical microscope. No destruction was seen. In addition, when human plasma and human whole blood (heparin-added 1200 U/100 ml 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 changes in plasma proteins were examined, decreases in complements such as albumin, C ₃ and C ₄ were all minimal. The adsorption of globulin by immobilized protein A is remarkable in all cases, with approximately 15 to 50
%Diminished. Even in experiments using whole blood, there were relatively few residual blood, thrombus formation, changes in blood cell counts, etc. Example 3 A homogeneous solution consisting of 100 g of vinyl acetate, 32.2 g of triallylisocyanurate (X = 0.25), 100 g of ethyl acetate, 100 g of n-heptanol, 6.6 g of polyvinyl acetate and 3.3 g of 2,2'-azobisisobutyronitrile The mixed solution was subjected to suspension polymerization in the same manner as in Example 1,
The obtained particles were subjected to a transesterification reaction.
The physical properties of the obtained gel are: average particle size 100μm, qOH=
12meq/g, W _R = 3.4g/g and specific surface area is 20
m ² /g. The exclusion limit molecular weight was measured in the same manner as in Example 1 and was found to be approximately 2 million. Activation was performed in the same manner as in Example 1, using protamine instead of immobilized protein A. The rest is the same as in Example 1. When the wet adsorbent was sterilized in an autoclave at 121°C for 20 minutes, almost no volume reduction was observed. Regarding the two types of adsorbents: sterile and non-sterile,
When human plasma was passed in the same manner as in Example 1, there was only a slight decrease in complements such as albumin, C ₃ and C ₄ , and the adsorption of immunoglobulin M by fixed protamine was confirmed by simple immunodiffusion When measured at

Claims (1)

[Scope of Claims] 1. An adsorbent for extracorporeal circulation therapy in which a porous particulate carrier covalently holds a ligand capable of binding to an adsorbed substance, wherein the porous particulate carrier has a hydrophilic cross-linking having a hydroxyl group. Made of organic synthetic polymer,
Water retention capacity is 0.5~6g/g, hydroxyl group density is 5~
When the carrier is in the range of 17 meq/g, the specific surface area of the carrier is at least 5 m ² /g, and the carrier is filled in a container with a diameter of 10 mm and a length of 50 mm and water is passed through the container, the inlet and outlet of the container are An adsorbent for extracorporeal circulation therapy, characterized in that it is a hard gel carrier with a volume reduction rate of 10% or less under a pressure difference of 200 mmHg. 2. The adsorbent for extracorporeal circulation treatment according to claim 1, wherein the hard gel carrier is a crosslinked synthetic polymer whose main constituent is vinyl alcohol units.