JPS6361024B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a carrier used in an adsorbent for body fluid purification. More specifically, the present invention relates to a carrier used in an adsorbent that specifically removes substances harmful to living organisms expressed in body fluids. As is well known, malignant substances such as autoantibodies, immune complexes, protein degradation products, bilirubin, and certain medium molecular weight substances expressed in body fluids are associated with cancer, immunoproliferative syndrome, rheumatoid arthritis, systemic lupus erythematosus, etc. It is believed to be closely related to the causes or progression of diseases and phenomena such as autoimmune diseases, allergies, and rejection reactions during organ transplants, as well as diseases and phenomena such as hepatitis and nephritis. . Therefore, by specifically adsorbing and removing the above-mentioned malignant substances from body fluid components such as blood and plasma, it is possible to prevent the progression of the above-mentioned diseases, alleviate symptoms, and further accelerate healing. was expected. The present inventors have discovered that they can specifically adsorb malignant substances such as autoantibodies and immune complexes with high efficiency, have little nonspecific adsorption, are safe, can be easily sterilized, and can be used in body fluids. As a result of intensive research aimed at providing adsorbents suitable for purification or regeneration, we have developed various types of adsorbents in which the carrier holds a substance with a special chemical structure that selectively interacts with the adsorbed substance. He discovered an adsorbent and filed a patent application (Japanese Patent Application No. 7152, No. 1983, No. 18923, No. 1983).
76776, patent application No. 56-159444). In addition, various studies were conducted regarding the carrier, and it was found that a hard gel with a specific surface area of at least 5 m ² /g is preferable as a carrier, and that a crosslinked synthetic polymer mainly composed of vinyl alcohol units has excellent performance. A patent application was previously filed for this heading (Japanese patent application No. 56-110817, Patent application No. 112919-1983). The present invention was made as a result of a more detailed study on a crosslinked synthetic polymer carrier mainly composed of vinyl alcohol units in connection with the previous invention, and relates to improvements to the above carrier. 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 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) Because it is a soft gel, when it is packed into a column and used for body fluid purification treatment, 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 flows 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 body fluid purification. 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 freeze-drying and cannot be restored 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
Thorough cleaning must be performed before use to prevent additives from entering body fluids. 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 body fluid purification, they are said to activate the complement system and the coagulation system, resulting in leukopenia, thrombocytopenia, etc., and are therefore not very desirable. As a result of intensive research into carriers for body fluid purification that overcome the drawbacks of conventional carriers, the present inventors have found that carriers with a specific surface area of at least 5 m ² /g exhibit good properties, and that they are mainly composed of vinyl alcohol units. It was discovered that cross-linked synthetic polymers with various components had excellent performance, and the earlier invention (Japanese Patent Application No. 56-110817;
56-112919), the present inventors conducted extensive research in order to provide a carrier with even better physical and chemical properties. the result,
After copolymerizing a carboxylic acid vinyl ester and a crosslinkable monomer having a triazine ring structure, the amounts of the carboxylic acid vinyl ester and the crosslinkable monomer in the crosslinked polyvinyl alcohol gel obtained by hydrolysis are adjusted to Products manufactured with a relatively high crosslinking degree of 0.35≦X≦0.8 have excellent mechanical strength, are hard, are difficult to deform, and have little pore destruction due to drying.
We found that it is thermally stable, and furthermore, we confirmed that although the gel itself is hydrophobic, there is little nonspecific adsorption of proteins that are useful to living organisms, such as albumin. , we have completed the present invention. That is, the present invention provides a carrier for use in an adsorbent for body fluid purification, which comprises a carboxylic acid vinyl ester and a crosslinkable monomer (1) having the following triazine ring structure.
or (2)

【formula】

[Formula] (R ₁ , R ₂ , R ₃ are -CH ₂ -CH=CH ₂ , -CH ₂ -C
≡CH or

(same _{or different} groups selected from [Formula] ₎ and _the degree _of crosslinking ^shown by _the following _{formula X 1} : Molecular weight of carboxylic acid vinyl ester M ₂ : Molecular weight of crosslinkable monomer W ₁ : Weight of carboxylic acid vinyl ester used in polymerization W ₂ : Weight of crosslinkable monomer used in polymerization n ₁ : Carboxylic acid Number of ethylenic double bonds in one molecule of vinyl ester n ₂ : After polymerization with the number of ethylenic double bonds in one molecule of crosslinkable monomer in the range of 0.35≦X≦0.80, hydrolysis is performed. This is the obtained adsorbent carrier for body fluid purification. A carrier suitable for the body fluid purification adsorbent of the present invention is obtained by copolymerizing a carboxylic acid vinyl ester and a compound having a triazine ring represented by the following formulas (1) or (2), and transesterifying or transesterifying the copolymer. Although it can be obtained by saponification, triallylisocyanurate is most preferred from the viewpoints of copolymerizability with carboxylic acid vinyl ester, strength of the formed matrix, micropore structure, and chemical stability.

【formula】

[Formula] (However, R ₁ , R ₂ and R ₃ are each independently,
CH ₂ =CH−CH ₂ −, CH≡C−CH ₂ − and

[Formula]) A carboxylic acid vinyl ester is a compound having one or more polymerizable carboxylic acid vinyl ester groups, and includes, for example, fatty acid vinyl such as vinyl acetate and vinyl propionate.
Polymerizable monomers such as diethylene glycol, ethyl vinyl ether, etc., which do not affect the properties of the body fluid purifying adsorbent of the present invention, may be added. In the carrier of the present invention, it is preferable to carry out copolymerization by selecting the amounts of carboxylic acid vinyl ester and crosslinkable monomer such that in the following formula (), X satisfies 0.35≦X≦0.8. X=W ₂ /M ₂ ×n ² /W ₁ /M ₁ ×n ₁ +W ₂ /M ₂ ×n ₂ … () (where M ₁ : Molecular weight of carboxylic acid vinyl ester M ₂ : Molecular weight of crosslinkable monomer Molecular weight W ₁ : Weight of carboxylic acid vinyl ester used in polymerization W ₂ : Weight of crosslinkable monomer used in polymerization n ₁ : Number of ethylenic double bonds in one molecule of carboxylic acid vinyl ester n ₂ : Crosslinking If X is smaller than 0.35 (the number of ethylenic double bonds that one molecule of the monomer has), it will become more hydrophilic as an adsorbent carrier and should have better affinity with body fluids, but mechanical This tends to cause the column to lose its hardness, making it susceptible to deformation and clogging when packed in a column and filled with highly viscous body fluids. In addition, the shrinkage rate upon drying increases, making pores more likely to be destroyed. When X is larger than 0.8, the adsorbent becomes a very hydrophobic carrier, which results in poor wettability with body fluids, and also makes it easier to activate the coagulation fibrinolytic system and complement system in the blood, and to inhibit albumin production. It becomes easier to adsorb useful proteins such as these in a non-specific manner. Also,
Since the density of functional groups capable of immobilizing a ligand becomes low, high-density immobilization of a ligand becomes impossible. On the other hand, when X is in the range of 0.35≦X≦0.8,
It has a large amount of hydroxyl group density, that is, a large number of functional groups capable of immobilizing ligands, has appropriate hydrophilicity, has excellent mechanical strength, has little shrinkage during drying, and has no pore destruction. It is difficult to heat, can be sterilized by heat, and has excellent properties as a carrier. As for the shape of the present carrier, any of the shapes such as spherical, granular, filamentous, hollow fiber, and flat membrane shapes can be effectively used.
A spherical or granular shape is particularly preferably used in view of the specific surface area of the carrier (corresponding to the adsorption capacity as an adsorbent) and the flow surface of body fluid during extracorporeal circulation. Therefore, the known suspension polymerization method is particularly effectively used as a method for synthesizing the carrier. The specific surface area is expressed as the surface occupied by nitrogen gas adsorbed per unit weight of dry gel. That is, 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 agarose, which has been 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 it has a soft mesh that is easily crushed, so even when it is packed into a column and used for body fluid purification treatment, it is not possible to flow body fluids at a high flow rate for a long 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. That is, it has permanent pores and has a higher specific surface area than soft gel. The carrier of the present invention exhibits a value of at least 5 m ² /g or more. 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. In order to maintain effective adsorption capacity and to stably flow liquids with high viscosity and high solute concentration, such as body fluids such as blood and plasma, at high flow rates for long periods of time, the average particle diameter (D _W ) of the carrier must be adjusted. 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 time. Therefore, the average particle diameter is preferably 25 to 2500 μm, more preferably 150 to 2500 μm, especially when used for whole blood.
It is 1500μm. The exclusion limit molecular weight (Mlim) of a hard gel carrier used as an adsorbent for body fluid purification may be set by taking into consideration the molecular weight of the substance to be held by the hard gel carrier through chemical bonds and the molecular weight of the target adsorbent. The carrier of the present invention is usually protein Mlim, with a concentration of 10 ³ to 10 ⁸ ,
Polyethylene glycol and dextran Mlim range from 3×10 ² to 3×10 ⁷ . protein
Mlim is a value indicating the lower limit of the molecular weight of molecules that cannot penetrate into the pores of the gel. Mlim can be measured by a known method by packing a gel into a column and using a standard protein with a known molecular weight. The chemical properties of the carrier used in the adsorbent for body fluid purification include (1) a high density of substances (ligands) that exhibit biological and/or chemical interactions with and can bind to the adsorbed substance; (2) The carrier has low nonspecific adsorption to plasma proteins, etc. so that it selectively adsorbs the target substance, (3) Complement system, coagulation, etc. (4) Furthermore, when used as an adsorbent for whole blood, interactions with blood cell components, such as thrombus formation, nonspecific adhesion of blood cell components, and residual Those with characteristics such as less blood etc. are preferable. Therefore, in addition to the physical properties already mentioned, a carrier that satisfies the above chemical properties is more preferably used. The carrier of the present invention satisfies the above characteristics well, but the hydroxyl group density of the carrier is 1 to 15 meq/
A range of g gives preferable results, especially between 2 and
Those in the range of 11 meq/g give more favorable 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 the reaction with the hydroxyl groups or the change in weight of the gel. 1g of dry gel is 1m
The hydroxyl group density when reacting with mol of acetic anhydride is
It is 1meq/g. The carrier of the present invention can be obtained by solution polymerization, suspension polymerization, emulsion polymerization, etc., but suspension polymerization is preferred because the shape of the adsorbent for body fluid purification is preferably spherical or granular. Suspension polymerization, for example, involves stirring a carboxylic acid vinyl ester and a crosslinking monomer in the coexistence of a solvent that dissolves these monomers but is difficult to dissolve in water to form small droplets, and polymerizing them. It is done. By adding an organic solvent that dissolves the monomer but is difficult to dissolve in water to the monomer, permanent pores are formed in the resulting copolymer. Organic solvents that dissolve monomers but are difficult to dissolve in water include aromatic hydrocarbons such as toluene and xylene, aliphatic hydrocarbons such as heptane and octane, ethyl acetate, and acetic acid.
-butyl, ester compounds such as n-hexyl acetate, ethers such as dibutyl ether, methyl isobutyl ketone, n-heptanol, etc. Organic solvent per 100 parts by weight of monomer
It is preferable to use it in a range of 20 to 300 parts by weight. A linear polymer soluble in the monomer mixture may be used in combination with the solvent to control the pore size or pore size distribution of the copolymer. Examples of linear polymers include polyvinyl acetate.
The linear polymer is used in an amount of 10 parts by weight or less per 100 parts by weight of the monomer. By using such a linear polymer in combination with the organic solvent, it becomes easy to obtain a gel with a larger pore size. The initiator used during polymerization may be a normal radical polymerization initiator,
For example, 2,2'-azobisisobutyronitrile, benzoyl peroxide, etc. can be used. The particulate polymer obtained by polymerization is then subjected to transesterification or saponification. The transesterification reaction or the saponification reaction is carried out using an acid or an alkali in water, alcohol, or a mixture thereof as a solvent. The temperature of the reaction is 5
-55°C is preferable, 10-50°C is more preferable,
Particularly preferred is 15-45°C. Gels obtained by transesterification or saponification can also be post-crosslinked, for example with epichlorohydrin, butanediol diglycidyl ether and the like. Any known method can be used to bind the ligand to the carrier of the present invention, such as covalent bonding, ionic bonding, physical adsorption, embedding, or precipitation insolubilization on the polymer surface. Therefore, it is preferable to use it by immobilizing it and making it insolubilized by covalent bonding. For this purpose, an immobilized enzyme, a known carrier activation method used in affinity chromatography, and a ligand binding method can be used. 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. However, in consideration of chemical stability, thermal stability, etc., it is preferable to use epoxide.
In particular, the epichlorohydrin method is recommended. Also,
If necessary, a molecule (spacer) of arbitrary length may be introduced between the carrier and the ligand. The ligand to be retained on the carrier of the present invention can be freely selected depending on the purpose, and some of them are exemplified below. For the treatment of systemic lupus erythematosus, adenine,
Homopolymers or copolymers of mono-, di-, and trinucleotides such as guanine, cytosine, uracil, and thymine, 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.
DNA 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 adsorption and removal of immune complexes in blood, complement components such as Clq, specific proteins such as protein A, and antibodies against immune complexes such as anti-heavistein constant region 2 phase 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 complement components such as Clq, specific proteins such as protein A, and immune complexes such as anti-heavichein constant region phase 2 antibodies can be used. For the treatment of Hashimoto's disease, thyroglobulin, a microsomal fraction component 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-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-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, protamine, heparin, antigens, antibodies, enzymes, Known substances capable of binding to adsorbed substances such as substrates and coenzymes can be used. Furthermore, the carrier of the present invention can also be used with two or more types of ligands retained therein. Furthermore, two or more types of carriers holding ligands can be used in combination. As described above, the carrier suitable for the adsorbent for body fluid purification of the present invention has sufficient mechanical strength, so it is difficult to prepare the adsorbent through activation, immobilization, transportation, extracorporeal circulation, and especially destruction. There is virtually no possibility of chipping, chipping, or chipping, and a wide range of operating methods and conditions can be selected. In addition, since it is a hard gel, when packed in a column and used for extracorporeal circulation,
Body fluids containing substances to be adsorbed or removed can be stably passed continuously for a long time at a high flow rate. Furthermore, since it is a hard gel and has permanent pores, it can be easily sterilized, which is an essential requirement 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. Furthermore, in addition to the above-mentioned physical properties, it had favorable chemical 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, and because it is highly hydrophilic, there is little nonspecific adsorption to plasma proteins and the like.
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 carrier of the present invention is applicable to general usage 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, allergic diseases such as bronchial asthma, diseases and phenomena related to the body's immune system such as rejection during organ transplantation, psoriasis, and ringworm. It can be effectively used for extracorporeal circulation treatment of skin diseases such as, kidney diseases such as nephritis, and liver diseases such as hepatitis. It can also be effectively used as a carrier for affinity chromatography. Embodiments of the present invention will be explained in more detail with reference to Examples below. Example 1 100 g of vinyl acetate, 64.3 g of triallyl isocyanurate (X = 0.40), 100 g of ethyl acetate, 100 g of heptane, 7.5 g of polyvinyl acetate (degree of polymerization 500) and 3.8 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 400 ml of water in which 1.5% by weight was dissolved into a flask, stir thoroughly, and then heat at 65°C for 18 hours and then at 75°C.
Suspension polymerization was carried out by heating and stirring for 5 hours to obtain a granular copolymer. After washing with water and extraction with acetone, the copolymer was transesterified in a solution consisting of 46.5 g of caustic soda and 2 methanol at 40° C. for 18 hours. The average particle size of the obtained gel was 150 μm, and the hydroxyl group density (qOH) per unit weight determined by the above method.
The molecular weight was 9.0 meq/g, the specific surface area was 60 m ² /g, and the exclusion limit molecular weight by dextran was 6×10 ⁵ . This gel was packed into two columns with an inner diameter of 10 mm and a length of 50 mm, and each column was filled with 0.4 ml of ACD-added healthy human plasma.
12 ml of ACD-added healthy human blood was flowed into the other tube at a flow rate of 0.7 ml/min. No decrease in packing volume, clogging, or decrease in flow rate was observed in either column, and the pressure difference before and after the column was 10 mm for plasma.
It was less than Hg, and blood was in the range of 10 to 20 mmHg. When we examined changes in plasma protein and blood cell components before and after passing through the column, we found that albumin was only slightly adsorbed in plasma, and there was little decrease in complement component _C3 . In other words, there was little non-specific adsorption of useful proteins. In addition, in blood, no significant difference was observed in the concentrations of red blood cells, white blood cells, and platelets before and after passing through the column. That is, almost no adhesion or hemolysis of blood cell components was observed. Next, 10 g (dry weight) of the obtained gel was suspended in 120 ml of dimethyl sulfoxide, and this was mixed with 78.3 ml of epichlorohydrin and 10 ml of 30% sodium hydroxide.
was added, and the activation reaction was carried out at 30°C for 5 hours with shaking and stirring. After the reaction was completed, it was collected with a glass filter, washed with dimethyl sulfoxide, and then washed with water to obtain an activated gel. The epoxy group density of the obtained gel was 1.1 meq/g (the epoxy group density was measured by reacting the gel with sodium thiosulfate in an aqueous solvent, and measuring the amount of sodium hydroxide produced by the reaction with the epoxy group). amount was measured and calculated from this). When this activated gel was compared with the original gel particles and observed under an optical microscope, no damage such as chipping or flaking was observed. Comparative Example 1 Sepharose 4B (manufactured by Pharmacia Huain Chemical Co., Ltd.), an agarose-based carrier commercially available as a water-insoluble carrier for affinity chromatography, was packed in the same column as in Example 1.
Plasma was run under the same conditions as in Example 1. As a result, the volume of Sepharose 4B in the column shrank by about 12%, and the pressure rose to over 20 mmHg. In addition, in order to measure the specific surface area, after replacing the solvent with acetone and drying at 60°C, the gels stuck to each other, contracted, and solidified. Example 2 Various crosslinking degrees X = 0.05, 0.25, 0.35, 0.50 were obtained by changing the charging ratio of vinyl acetate and triallyl isocyanurate using the same manufacturing method as the polymerization method and saponification method shown in Example 1. , 0.80, 0.9
(Among these, gels with X=0.05, 0.25 and 0.9 were used as comparative examples for Example 2). The physical properties of these gels are shown in the table below.

[Table] From the table above, when X is smaller than 0.35, the specific surface area becomes smaller due to shrinkage during drying, and
It can be seen that when it is larger than 0.8, the hydroxyl group density becomes very small, and the degree of crosslinking X is 0.35≦X≦
A gel in the range of 0.80 has a large hydroxyl group density and a large specific surface area. These gels were packed into a column with an inner diameter of 10 mm and a length of 50 mm, and the shrinkage rate of the gel volume (column capacity) was measured when the differential pressure between the inlet and outlet of the column was set to 150 mmHg while water was flowing. The results are shown in FIG. From FIG. 1, when the degree of crosslinking X becomes smaller than 0.35, the gel becomes soft and the volume shrinkage rate of the gel (corresponding to the degree to which the column becomes clogged) increases. Next, 2 ml of these gels (column volume) were placed in an Erlenmeyer flask, 6 ml of healthy human plasma was added, and the mixture was shaken at 37°C for 3 hours. Plasma was then separated from the gel and analyzed for albumin and complement _C3 . The evaluation methods are: albumin using bromcresol green; complement _C3 using single, radial,
It was based on the Imiyuno Diffusion Method. The results are shown in Figures 2 and 3, where the vertical axis shows the concentration of plasma after treatment (after correcting for dilution due to water in the adsorbent), and the broken line shows the value of the plasma used in the adsorption experiment. . That is, when the degree of crosslinking X is greater than 0.8,
Adsorption of proteins useful to living organisms such as albumin and complement _C3 increases. From the above results, when the degree of crosslinking It can be seen that there is little non-specific adsorption of proteins useful to living organisms. Example 3 Gel obtained in the same manner as Example 1 (crosslinking degree
= 0.4) was sterilized in an autoclave at 121°C for 20 minutes in a wet state, but the physical properties of the adsorbent hardly changed.

[Brief explanation of drawings]

FIG. 1 is a graph showing the measurement results of gel volume shrinkage in Example 2, FIG. 2 is a graph showing the results of Albun analysis in the adsorption experiment of Example 2,
FIG. 3 is a graph showing the results of analysis of complement _C3 .

Claims (1)

[Scope of Claims] 1. A carrier used in an adsorbent for body fluid purification, which comprises a carboxylic acid vinyl ester and a crosslinkable monomer (1) or (2) having the following triazine ring structure [Formula] [Formula] ( R ₁ , R ₂ , R ₃ are −CH ₂ −CH=CH ₂ , −CH ₂ −C
_≡CH or _the same or different groups selected from [Formula] ₎ and _{the degree} of crosslinking _shown by _the following _formula X n ₂ M ₁ : Molecular weight of carboxylic acid vinyl ester M ₂ : Molecular weight of crosslinkable monomer W ₁ : Weight of carboxylic acid vinyl ester used in polymerization W ₂ : Weight of crosslinkable monomer used in polymerization n ₁ : Number of ethylenic double bonds in one molecule of carboxylic acid vinyl ester n ₂ : After polymerization with the number of ethylenic double bonds in one molecule of crosslinkable monomer in the range of 0.35≦X≦0.80, hydration Adsorbent carrier for body fluid purification obtained by decomposition.