JP5748977B2 - Water-insoluble carrier obtained by polymerizing monomers derived from amino acids - Google Patents

Description

  The present invention relates to a method for producing a water-insoluble carrier obtained by polymerizing a monomer derived from an amino acid, which can be used as a medical adsorbent, and adsorption of an immunoglobulin adsorbent and / or an immunoglobulin complex using the same. Related to the vessel.

  Dilated cardiomyopathy (DCM) is a disease in which the contraction of the ventricular muscles becomes extremely poor and the heart expands, and the prognosis is extremely poor compared to hypertrophic cardiomyopathy. In Japan, about 50% of people have survived for 5 years since diagnosis. In the treatment of dilated cardiomyopathy, heart transplantation is desired as a radical treatment method, but the number provided is insufficient with respect to the number of waiting, and symptomatic treatment for heart failure is mainly used. Moreover, although the case where cardiac function and prognosis improve by administration of an angiotensin converting enzyme (ACE) inhibitor and (beta) blocker has been reported, the more effective therapeutic agent and therapeutic method are desired. In recent years, a variety of immunoglobulins and / or immunoglobulin complexes reactive with self have been detected in the blood of DCM patients, and data that triggers the onset of DCM have been reported.

  Also present in blood in rheumatoid arthritis, systemic lupus erythematosus, Guillain-Barre syndrome, idiopathic thrombocytopenic purpura, or other diseases such as glomerulonephritis, organ transplant rejection, tumors, infections, etc. It is becoming apparent that immunoglobulins and / or immunoglobulin complexes that are closely related to the cause or progression of these diseases and phenomena.

  Therefore, it is expected that by adsorbing and removing immunoglobulins and / or immunoglobulin complexes from body fluids such as blood and plasma, the progression of the above diseases can be prevented, the symptoms can be reduced, and further healing can be promoted. There have been attempts to use some adsorption removing materials. For example, a separation medium in which protein A having binding ability to immunoglobulin is immobilized on a matrix is known as an adsorbent having high specificity for immunoglobulin G and its immunoglobulin complex (Patent Document 1). Further, an adsorbent for immunoglobulin and / or immunoglobulin complex in which a hydrophobic compound is immobilized on an insoluble carrier (Patent Document 2) has already been clinically applied in Japan.

  However, the adsorbents that have been tried so far, such as the above protein A adsorbent, are used in contact with body fluids because the ligand protein A is a heterologous protein having a molecular weight of about 42,000 daltons derived from S. aureus. There is a risk of side effects arising from the antigenicity due to elution of protein A, there are problems with stability during sterilization, the sterilization method is limited, storage stability after immobilization, etc. There are drawbacks. In addition, since the ligand protein A is very expensive, it is assumed to be reused, and there are many other disadvantages such as limited use for plasma treatment and concerns about safety. . In addition, the adsorbent for immunoglobulins and / or immunoglobulin complexes described in JP-A-57-122875 has poor blood compatibility because it has a hydrophobic compound immobilized thereon, and whole blood containing blood cell components. Has the disadvantage that it cannot be processed.

  Thus, the adsorbents for adsorbing conventionally known immunoglobulins and / or immunoglobulin complexes still have many problems from the viewpoint of safety, stability, cost, blood compatibility and the like. .

Special table 2000-500649 gazette Japanese Patent Laid-Open No. 9-77790

  An object of the present invention is to provide a water-insoluble carrier that can be used as an adsorbent for immunoglobulins and / or immunoglobulin complexes that does not require a ligand immobilization step, and a method for producing the same. Another object of the present invention is to provide a method for removing immunoglobulins and / or immunoglobulin complexes using the water-insoluble carrier, and an adsorber.

  As a result of intensive studies on the above problems, the present inventor has found that a water-insoluble carrier obtained by polymerizing a monomer derived from an amino acid can efficiently adsorb immunoglobulin and / or immunoglobulin complex, The present invention has been completed.

That is, the present invention relates to the following inventions.
(1) A method of removing blood immunoglobulin and / or immunoglobulin complex by bringing blood into contact with a water-insoluble carrier,
The water-insoluble carrier is comprised by polymerizing a monomer polymer, wherein the at least one or more monomers, immunoglobulin and blood, which is a monomer derived from an amino acid A method for removing the immunoglobulin complex .
(2) The blood according to (1), wherein the polymer is obtained by polymerizing a monomer mixture containing a monomer derived from an amino acid and at least one monomer other than the monomer. Of removing immunoglobulins and / or immunoglobulin complexes .
( 3 ) The immunoglobulin derived from amino acid and / or immunoglobulin according to ( 1) or (2), wherein the monomer derived from an amino acid is a methacrylic acid and an amino acid covalently bonded to each other How to remove the complex .
( 4 ) The immunoglobulin in blood according to (2), wherein the monomer other than the monomer derived from an amino acid is at least one of methacrylic acid, methyl methacrylate, styrene, and vinyl acetate And / or a method for removing an immunoglobulin complex .
( 5 ) The immunoglobulin in blood according to any one of (1) to ( 4 ), wherein the amino acid is at least one selected from tryptophan, phenylalanine, tyrosine, histidine or an analog thereof A method for removing an immunoglobulin complex .
( 6 ) Blood immunoglobulin and / or immunoglobulin complex, which has a liquid inlet and outlet and is filled with a water-insoluble carrier in a container provided with means for preventing the water-insoluble carrier from flowing out of the container. A body adsorber,
The water-insoluble carrier is comprised by polymerizing a monomer polymer, wherein the at least one or more monomers, immunoglobulin and blood, which is a monomer derived from an amino acid Adsorber for immunoglobulin complex .
( 7 ) The blood according to ( 6 ), wherein the polymer is obtained by polymerizing a monomer mixture containing a monomer derived from an amino acid and at least one monomer other than the monomer. An immunoglobulin and / or an immunoglobulin complex adsorber .
( 8 )
The monomer derived from an amino acid, wherein methacrylic acid and an amino acid are covalently bonded to each other , wherein the immunoglobulin and / or immunoglobulin complex in blood according to ( 6) or (7) Adsorber .
( 9 )
( 7 ) The immunoglobulin and / or immunity in blood according to ( 7 ), wherein the monomer other than the monomer derived from an amino acid is at least one of methacrylic acid, methyl methacrylate, styrene, and vinyl acetate. Adsorber for globulin complex .
( 10 )
The immunoglobulin and / or immunoglobulin complex in blood according to any one of ( 6 ) to ( 9 ), wherein the amino acid is at least one selected from tryptophan, phenylalanine, tyrosine, histidine or an analog thereof Body adsorber .

  ADVANTAGE OF THE INVENTION According to this invention, the adsorbent of an immunoglobulin and / or an immunoglobulin complex which does not require a ligand fixation process can be obtained. Since this adsorbent does not require peptides or proteins and further does not require a ligand immobilization step, it can be produced at a very low cost. Therefore, the present invention is a novel material and method that is completely different from existing materials and existing methods, and is expected to contribute deeply to the medical field.

It is a schematic sectional drawing of one Example of the adsorption device packed with the support | carrier in this invention.

  The best mode of the present invention will be described in detail below, but the present invention is not limited to the following description.

  The monomer containing an amino acid in the present invention is specifically a compound in which methacrylic acid and an amino acid are covalently bonded. In terms of carrier synthesis and affinity for immunoglobulins and / or immunoglobulin complexes, methacrylic acid and amino acids can be linkers even though they are directly covalently bonded, such as the carboxylic acid of methacrylic acid and the amino group of the amino acid being linked by an amide bond. Although it may be covalently bonded indirectly, the former is preferred from the viewpoint of monomer production. Furthermore, since the monomer is polymerized, it needs to have a double bond such as methacrylic acid.

  The amino acid in the present invention is an amino acid having a cyclic structure having affinity for immunoglobulin and / or immunoglobulin complex, and specifically, an amino acid having a cyclic side chain such as tryptophan, phenylalanine, tyrosine, histidine. . The tryptophan derivatives, phenylalanine derivatives, tyrosine derivatives, and histidine derivatives in the present invention refer to hydrophobic amino acid esters such as tryptophan ethyl ester and tryptophan methyl ester, and hydrophobic amino acid derivatives having an indole ring such as tryptoamine and tryptophanol. However, the present invention is not limited to these. These amino acids and derivatives thereof may be L-form, D-form, DL-form, or a mixture thereof. Further, it may be a mixture of two or more. Among these amino acids and derivatives thereof, the first two are natural amino acids and high safety, the second is high affinity for immunoglobulins and / or immunoglobulin complexes, More preferably L-tryptophan is used.

  The monomer containing no amino acid in the present invention is a monomer literally containing no amino acid such as methacrylic acid, methyl methacrylate, styrene, and vinyl acetate, and can be polymerized with the monomer containing the amino acid. It is necessary to have a double bond.

  The water-insoluble carrier in the present invention means a solid at room temperature and normal pressure and water-insoluble. The shape of the water-insoluble carrier in the present invention is not particularly limited, and the size thereof is not particularly limited, such as a spherical shape, a granular shape, a thread shape, a hollow shape, and a flat membrane shape. Since the water-insoluble carrier has a higher performance for immunoglobulins and / or immunoglobulin complexes as the specific surface area is larger, a spherical or granular form is particularly preferably used. The spherical or granular carrier is preferably a carrier having a large number of pores of an appropriate size, that is, a porous structure. A carrier having a porous structure is naturally a carrier having a space (macropore) formed by agglomeration of microspheres when the base polymer matrix forms one spherical particle by agglomeration of microspheres. However, in the case of a carrier having pores formed between agglomerates of nuclei in one microsphere constituting the basic polymer matrix, or a carrier having a three-dimensional structure (polymer network). The case of a carrier having pores (micropores) existing when the polymer is swollen with an affinity organic solvent is also included.

  In view of the adsorptive capacity per unit volume of the adsorbent, the water-insoluble carrier having a porous structure preferably has total porosity rather than surface porosity, and the pore volume and specific surface area are such that the adsorptivity is not impaired. Is preferably large.

  When the water-insoluble carrier is spherical or granular, the average particle size of the carrier is better as the adsorbent of the present invention is treated with whole blood, but the smaller the average particle size is better in terms of adsorption efficiency. As the adsorbent in the present invention, the average particle size of the adsorbent capable of exhibiting whole blood treatment and good adsorption performance is preferably 100 μm or more and 1000 μm or less, and more preferable from the viewpoint that good blood cell permeability and adsorption performance can be exhibited. Is 200 μm or more and 800 μm or less, more preferably 400 μm or more and 600 μm or less.

  The water-insoluble carrier may be cross-linked for the purpose of increasing the strength. Examples of the crosslinking agent include triallyl isocyanurate (TAIC), ethylene glycol dimethacrylate (EGDMA), and glycerin dimethacrylate (GDMA), but the present invention is not limited thereto.

  As the polymerization method of the water-insoluble carrier described in the present invention, suspension polymerization, uniform droplet formation, and the like can be considered, but the present invention is not limited to these. For example, in the case of polymerizing with two or more types of monomers, a method of polymerizing in the presence of two types of monomers at the same time may be used. First, only one type is polymerized and the second type of monomer is polymerized like seed polymerization. The method may be used and is not limited to the polymerization method.

  Examples of the immunoglobulin and / or immunoglobulin complex in the present invention include autoantibodies and / or immune complexes in autoimmune diseases. More specifically, rheumatoid factor, antinuclear antibody, anti-DNA antibody, anti-lymphocyte antibody, anti-erythrocyte antibody, anti-platelet antibody, anti-acetylcholine receptor antibody, serum withdrawal antibody, anti-thyroglobulin antibody, anti-microsomal antibody, anti-colon Autoantibodies such as antibodies, anti-smooth muscle antibodies, anti-epidermal cells, anti-basement membrane antibodies, anti-proteoglycan antibodies, anti-collagen antibodies, anti-gastric factor antibodies, anti-thyroid microsomal antibodies, anti-arterial antibodies, anti-adrenoceptor antibodies And / or immune complexes thereof.

  The simplest method for adsorbing immunoglobulins and / or immunoglobulin complexes using the adsorbent of the present invention is to take out blood and store it in a bag or the like, and mix the adsorbent with it to form a malignant substance. There is a method of obtaining blood from which malignant substances have been removed by separating the adsorbent after adsorbing the adsorbent. This method can also be applied to the production of pharmaceuticals (eg, blood products, vaccines, genetically modified products) or medical materials using blood as a raw material. The next method has a blood inlet and outlet, and there is a method in which the adsorbent is filled in a container equipped with a filter through which blood passes but the adsorbent does not pass, and the blood flows therethrough. Either method can be used, but the latter method is easy to operate, and by incorporating it into an extracorporeal circuit, it is possible to efficiently remove malignant substances from the patient's blood online. In particular, since the adsorbent of the present invention has a very high blood compatibility, blood containing a blood cell component can be directly processed without the need for plasma separation. . In addition, the adsorbent can be used alone in the extracorporeal circuit, but can also be used in combination with other extracorporeal circulation treatment systems. Examples of the combination include an artificial dialysis circuit and the like, and can also be used in combination with dialysis therapy.

  Next, an example of online extracorporeal circulation will be described with reference to FIG. 3 which is a schematic sectional view. In FIG. 3, 1 is a liquid inlet, 2 is a liquid outlet, 3 is an adsorbent according to the present invention, 4 and 5 are filters through which liquid and components contained in the liquid can pass, but 3 adsorbents cannot pass. , 6 is a column, and 7 is an adsorber. However, the adsorber as an extracorporeal circulation is not limited to such a specific example, and the adsorber is provided in a container having an inlet and an outlet for liquid and a device for preventing the adsorbent from flowing out of the container. Any material may be used as long as it is filled with a material.

  Examples of the anti-spill tool include filters such as mesh, non-woven fabric, and cotton plug. The shape, material, and size of the container are not particularly limited, but a cylindrical container is preferable as the shape. Preferred materials for the container are materials having sterilization resistance, and specific examples include silicon-coated glass, polypropylene, vinyl chloride, polycarbonate, polysulfone, and polymethylpentene. The capacity of the container is preferably 50 ml or more and 1500 ml or less, and the diameter is preferably 2 cm or more and 20 cm or less. If the capacity of the container is smaller than 50 ml, the adsorption amount is not sufficient, and if it is larger than 1500 ml, the extracorporeal circulation amount is increased, which is not preferable. If the diameter of the container is smaller than 2 cm, the linear velocity increases, so that the pressure loss increases, which is not preferable. If it is larger than 20 cm, it becomes difficult to handle and the linear velocity becomes small, which is not preferable because there is a risk of solidification. From the viewpoint of having an effective adsorption amount and excellent safety, the volume is 100 ml or more and 800 ml or less, the diameter is more preferably 3 cm or more and 15 cm or less, the volume is 150 ml or more and 400 ml or less, and the diameter is 4 cm or more. 10 cm or less is particularly preferable.

  EXAMPLES Hereinafter, although an Example demonstrates in detail regarding this invention, this invention is not limited only to a following example.

Example 1
45 g of vinyl acetate, 13.95 g of triallylic isocyanurate, 23.85 g of heptane, 51.75 g of ethyl acetate, 4.32 g of polyvinyl acetate (degree of polymerization 400), and a polymerization initiator 2,2′-azobis (2, 4-dimethylvaleronitrile) (V-65) 2.25 g of a homogeneous mixed solution, 0.045 g of polyvinyl alcohol, 0.0099 g of sodium alpha olefin sulfonate, 2.26 g of particulate calcium triphosphate, 0 of sodium nitrite The solution was added to a 2 L separable flask having a flat stirring blade and two baffle plates in which an aqueous phase containing 303.39 mL of water in which 0.0171 g was dissolved was previously charged, and reacted at 65 ° C.

  Two hours later, a solution obtained by dissolving 18.0 g of methacryloyl L-tryptophan in acetone was added little by little to the reaction solution in the separable flask and further reacted at 65 ° C. for 3 hours.

  Next, hydrochloric acid was added to the contents of the separable flask to adjust the pH to 2 or less to dissolve the tribasic calcium phosphate, and then washed well with water. After confirming that the pH of the cleaning liquid was close to neutral, water was replaced with acetone, and the polymer was thoroughly washed with acetone. Next, acetone was replaced with water, and then an amount of sodium hydroxide (NaOH) of the following formula was added as an aqueous solution so as to be excessive with respect to the vinyl acetate unit.

NaOH (solid weight) = particle dry weight / 86.09 × 40 × 1.5
The amount of water was adjusted so that the NaOH concentration relative to water was 4% by weight. This was saponified with stirring at a reaction temperature of 40 ° C. for 6 hours. Then, it washed with water until pH of the washing | cleaning liquid became neutrality, and also wash | cleaned fully with 80 degreeC warm water. Next, autoclave treatment at 121 ° C. for 20 minutes was performed to obtain clean crosslinked polymer particles. When the amount of immobilized tryptophan was measured by non-aqueous titration, it was 47.5 μmol per mL of swelling volume.

(Example 2)
A homogeneous mixed solution composed of 50 g of vinyl acetate, 15.50 g of triallyl isocyanurate, 26.50 g of heptane, 57.50 g of ethyl acetate, 4.80 g of polyvinyl acetate (degree of polymerization 400), and 2.50 g of V-65 A flat plate in which an aqueous phase containing 337.10 mL of water in which 0.050 g of polyvinyl alcohol, 0.0110 g of sodium alpha olefin sulfonate, 2.51 g of fine particulate calcium phosphate, and 0.0190 g of sodium nitrite are dissolved is prepared in advance. Was added to a 2 L separable flask having a stirrer blade and two baffle plates, and reacted at 65 ° C.

  Two hours later, a solution of 20.0 g of methacryloyl L-tryptophan, 10.0 g of triallylic isocyanurate, and 2.5 g of V-65 in acetone was added little by little to the reaction solution in the separable flask, The reaction was further carried out at 65 ° C. for 3 hours.

  Next, post-treatment similar to that in Example 1 was performed to obtain clean crosslinked polymer particles. When the amount of immobilized tryptophan was measured by nonaqueous titration, it was 36.8 μmol per mL of swelling volume.

(Example 3)
A homogeneous mixed solution composed of 45 g of vinyl acetate, 22.50 g of triallyl isocyanurate, 26.10 g of heptane, 58.50 g of ethyl acetate, 2.88 g of polyvinyl acetate (degree of polymerization 400), and 2.25 g of V-65 , A flat plate in which an aqueous phase containing 338.04 mL of water in which 0.050 g of polyvinyl alcohol, 0.0108 g of sodium alpha olefin sulfonate, 2.52 g of particulate tribasic calcium phosphate, and 0.0189 g of sodium nitrite are dissolved is prepared in advance. Was added to a 2 L separable flask having a stirrer blade and two baffle plates, and reacted at 65 ° C.

  After 2 hours, a solution prepared by dissolving 18.0 g of methacryloyl L-tryptophan and 2.25 g of V-65 in acetone was added little by little to the reaction solution in the separable flask, and further reacted at 65 ° C. for 3 hours. .

  Next, post-treatment similar to that in Example 1 was performed to obtain clean crosslinked polymer particles. When the amount of immobilized tryptophan was measured by nonaqueous titration, it was 54.0 μmol per mL of swelling volume.

Example 4
A homogeneous mixed solution composed of 45 g of vinyl acetate, 22.50 g of triallyl isocyanurate, 26.10 g of heptane, 58.50 g of ethyl acetate, 2.88 g of polyvinyl acetate (degree of polymerization 400), and 2.25 g of V-65 , A flat plate in which an aqueous phase containing 338.04 mL of water in which 0.050 g of polyvinyl alcohol, 0.0108 g of sodium alpha olefin sulfonate, 2.52 g of particulate tribasic calcium phosphate, and 0.0189 g of sodium nitrite are dissolved is prepared in advance. Was added to a 2 L separable flask having a stirrer blade and two baffle plates, and reacted at 65 ° C.

  Two hours later, a solution prepared by dissolving 18.0 g of methacryloyl L-tryptophan, 4.50 g of triallylic isocyanurate, and 2.25 g of V-65 in acetone was added little by little to the reaction solution in the separable flask, The reaction was further carried out at 65 ° C. for 3 hours.

  Next, post-treatment similar to that in Example 1 was performed to obtain clean crosslinked polymer particles. When the amount of immobilized tryptophan was measured by nonaqueous titration, it was 50.5 μmol per mL of swelling volume.

(Example 5)
A homogeneous mixed solution composed of 50 g of vinyl acetate, 15.50 g of triallyl isocyanurate, 26.50 g of heptane, 57.50 g of ethyl acetate, 4.80 g of polyvinyl acetate (degree of polymerization 400), and 2.50 g of V-65 A flat plate in which an aqueous phase containing 337.10 mL of water in which 0.050 g of polyvinyl alcohol, 0.0110 g of sodium alpha olefin sulfonate, 2.51 g of fine particulate calcium phosphate, and 0.0190 g of sodium nitrite are dissolved is prepared in advance. Was added to a 2 L separable flask having a stirrer blade and two baffle plates, and reacted at 65 ° C.

  Two hours later, a solution of 20.0 g of methacryloyl L-tryptophan and 5.0 g of ethylene glycol dimethacrylate in acetone was added little by little to the reaction solution in the separable flask, and further reacted at 65 ° C. for 3 hours. It was.

  Next, post-treatment similar to that in Example 1 was performed to obtain clean crosslinked polymer particles. When the amount of immobilized tryptophan was measured by nonaqueous titration, it was 53.3 μmol per mL of swelling volume.

(Example 6)
A homogeneous mixed solution composed of 45 g of vinyl acetate, 13.95 g of triallylic isocyanurate, 23.85 g of heptane, 51.75 g of ethyl acetate, 4.32 g of polyvinyl acetate (degree of polymerization 400), and 2.25 g of V-65 A flat plate preliminarily charged with an aqueous phase containing 303.39 mL of water in which 0.045 g of polyvinyl alcohol, 0.0099 g of sodium alpha olefin sulfonate, 2.26 g of finely divided calcium triphosphate and 0.0171 g of sodium nitrite are dissolved Was added to a 2 L separable flask having a stirrer blade and two baffle plates, and reacted at 65 ° C.

  Two hours later, a solution obtained by dissolving 18.0 g of methacryloyl L-tryptophan in acetone was added little by little to the reaction solution in the separable flask and further reacted at 65 ° C.

  After 2 hours, the number of stirring was increased, and uniform consisting of 16.2 g vinyl acetate, 5.1 g heptane, 9.77 g ethyl acetate, 1.55 g polyvinyl acetate (degree of polymerization 400) and 0.81 g V-65. The mixed solution was added little by little to the reaction solution in the separable flask and further reacted at 65 ° C. for 4 hours.

  Next, post-treatment similar to that in Example 1 was performed to obtain clean crosslinked polymer particles. When the amount of immobilized tryptophan was measured by nonaqueous titration, it was 38.5 μmol per mL of swelling volume.

(test)
Each carrier obtained in Examples 1 to 6 was swelled to collect 0.5 mL, added with 3.3 mL of plasma anticoagulated with citric acid, and shaken at 37 ° C. for 2 hours. Similarly, the concentration of immunoglobulin G in the plasma not shaken with the carrier and similarly shaken at 37 ° C. for 2 hours and the plasma after contact with the carrier were measured. Table 1 shows the results of the immunoglobulin G concentration not in contact with the carrier under the same conditions as the immunoglobulin G concentration in the plasma contacted with each carrier.

1. 1. Liquid inlet 2. Liquid outlet Carrier 4,5. 5. Filter that can pass liquid and components contained in liquid but cannot pass carrier. Column 7. Adsorber

Claims (12)

The water-insoluble carrier is brought into contact with blood to a method for removing immunoglobulins and / or immunoglobulin complexes in the blood,
The water-insoluble carrier is composed of a polymer obtained by polymerizing monomers,
At least one of the monomers is a monomer (1) in which a carboxylic acid of methacrylic acid and an amino group of an amino acid are directly amide-bonded, and immunoglobulin and / or immunoglobulin complex in blood How to remove the body. Monomer containing at least one or more monomers (1) in which the polymer has a amide bond between the carboxylic acid of methacrylic acid and the amino group of the amino acid, and the monomer (2) other than the monomer (1). The method for removing immunoglobulins and / or immunoglobulin complexes in blood according to claim 1, wherein the body mixture is polymerized. 3. The polymer according to claim 2, wherein the polymer is obtained by first polymerizing a monomer (2) other than the monomer (1) and then polymerizing the monomer (1). A method for removing immunoglobulins and / or immunoglobulin complexes in blood. The method for removing immunoglobulins and / or immunoglobulin complexes in blood according to claim 2 or 3 , wherein the polymer is obtained by polymerizing vinyl acetate as at least the monomer (2) and then saponifying the polymer . The method for removing immunoglobulins and / or immunoglobulin complexes in blood according to any one of claims 1 to 4, wherein the polymer is crosslinked with triallyl isocyanurate, ethylene glycol dimethacrylate or glycerin dimethacrylate. . Amino acids tryptophan, phenylalanine, tyrosine, histidine or immunoglobulin and / or immunoglobulin complexes in the blood according to claim 1, wherein the 5 that is at least one selected from analogues thereof Removal method. Adsorption of immunoglobulins and / or immunoglobulin complexes in blood, which has a liquid inlet and outlet and is filled with a water-insoluble carrier in a container provided with means for preventing the water-insoluble carrier from flowing out of the container A vessel,
The water-insoluble carrier is composed of a polymer obtained by polymerizing monomers,
At least one of the monomers is a monomer (1) in which a carboxylic acid of methacrylic acid and an amino group of an amino acid are directly amide-bonded, and immunoglobulin and / or immunoglobulin complex in blood Body adsorber. Monomer containing at least one or more monomers (1) in which the polymer has a amide bond between the carboxylic acid of methacrylic acid and the amino group of the amino acid, and the monomer (2) other than the monomer (1). The adsorber for immunoglobulins and / or immunoglobulin complexes in blood according to claim 7 , wherein the body mixture is polymerized. 9. The polymer according to claim 8, wherein the polymer is obtained by first polymerizing a monomer (2) other than the monomer (1) and then polymerizing the monomer (1). Adsorber for immunoglobulins and / or immunoglobulin complexes in the blood. The adsorber for immunoglobulins and / or immunoglobulin complexes in blood according to claim 8 or 9, wherein the polymer is obtained by polymerizing vinyl acetate as at least the monomer (2) and then saponifying the polymer . The adsorber for immunoglobulins and / or immunoglobulin complexes in blood according to any one of claims 7 to 10, wherein the polymer is crosslinked with triallyl isocyanurate, ethylene glycol dimethacrylate or glycerin dimethacrylate. . The amino acid is at least one selected from tryptophan, phenylalanine, tyrosine, histidine or an analog thereof, and the immunoglobulin and / or immunoglobulin complex in blood according to any one of claims 7 to 11 Adsorber.

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