JP3084436B2 - Anti-DNA antibody removal device - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an anti-DN
The present invention relates to a removal device for adsorbing and removing or recovering the A antibody. 2. Description of the Related Art Autoimmune diseases are, as their names suggest, antibodies in which an antibody against a component of the own tissue (hereinafter referred to as autoantibody) appears. In systemic lupus erythematosus (hereinafter, referred to as SLE), which is a typical autoimmune disease, antibodies (hereinafter, referred to as anti-DNA antibodies) against nuclear components of cells, particularly, deoxyribonucleic acid (hereinafter, referred to as DNA) appear in body fluids, It is known to be closely related to the condition.
The mechanism by which the produced autoantibodies are involved in the pathogenesis of the disease is not always clear, but the mechanism by which the autoantibodies themselves damage cells or the autoantibodies bind to antigens to form immune complexes and deposit on tissues A mechanism that causes organizational disability due to this has been proposed. In the case of SLE, the generated anti-DNA antibody forms an immune complex with the DNA derived from the cells also spilled into the blood and deposits on the blood vessel wall, renal glomerulus, etc., causing vasculitis and lupus nephritis, respectively. In fact, in many cases, SLE dies from renal failure. [0003] As described above, various symptoms are caused by the produced anti-DNA antibody or the immune complex of the antibody and DNA.
Control of NA antibodies is very important. Conventionally, steroids, immunosuppressants, immunomodulators, anti-inflammatory agents and the like have been widely used for the treatment of SLE for the purpose of suppressing the production of anti-DNA antibodies. Among them, steroids are most commonly used, and a short-term ultra-high dose steroid therapy called pulse therapy is often performed. However, since steroids are liable to cause side effects even when administered in a small amount, it is obvious that short-term ultra-high dose administration of steroids tends to cause even greater side effects. In addition, these drugs are often used for a long period of time, and in such cases, side effects are more likely to occur, and in some cases, the dose must be gradually increased due to drug resistance. There are many cases where it is impossible to use or does not exert a sufficient effect. In particular,
Although the active phase of SLE is the time when anti-DNA antibody suppression is most necessary, there are many cases where a strong therapy using a drug such as pulse therapy or an immunosuppressant cannot be adopted for the above reasons. On the other hand, as an approach different from these drug therapies, attempts have been made to directly remove anti-DNA antibodies in body fluids by extracorporeal circulation. The simplest method is the so-called plasma exchange therapy in which the plasma of a patient containing an anti-DNA antibody is replaced with the plasma of a healthy person. According to this method, anti-DNA antibodies in blood are significantly reduced, and symptoms have been improved. However, this method requires a large amount of healthy plasma, is not only expensive, but has not been widely used due to the risk of infection such as serum hepatitis during the treatment. [0006] In plasma exchange therapy, all components in plasma are removed and exchanged with healthy plasma. On the other hand, in order to selectively remove anti-DNA antibodies as pathogenic substances, molecular exchange is performed. A plasma separation membrane method has been developed to separate pathogens by size. In this method, plasma is separated by a membrane into a high molecular weight fraction and a low molecular weight fraction, the high molecular weight fraction containing the pathogenic substance is discarded, and the low molecular weight fraction containing albumin, the main protein, is separated. Return to patient, anti-DNA
Antibodies are mainly IgG (immunoglobulin G) having a molecular weight of about 160,000. Since the molecular weight is close to that of albumin (molecular weight of about 60,000), separation between the two is poor, and a large amount of albumin is removed when removing anti-DNA antibodies. In addition, there is a disadvantage that all proteins having a molecular weight equal to or higher than the pathogenic substance are removed. [0007] Therefore, there has been a demand for a means of removing the anti-DNA antibody, which is a pathogenic substance, more selectively so that other useful components in the body fluid are hardly lost. Means for Solving the Problems The inventors of the present invention have conducted intensive studies in view of the above circumstances, and as a result, have found that the anti-DNA antibody can be selectively adsorbed without losing the active ingredient in the body fluid. He found the body and completed the present invention. Accordingly, the present invention is a container having an inlet and an outlet of the fluid, but components contained in the fluid and the fluid can pass, the water-insoluble porous material in molecular weight of 1,000 or more sulfated polysaccharides The present invention relates to a filter through which an adsorbent of an immobilized anti-DNA antibody cannot pass, and a device for removing an anti-DNA antibody comprising an adsorbent of the anti-DNA antibody filled in the container. BEST MODE FOR CARRYING OUT THE INVENTION In the present specification, a body fluid refers to blood, plasma, serum, ascites, lymph fluid, intra-articular fluid and fraction components obtained therefrom, and other liquid components derived from living organisms Say. The water-insoluble porous material used in the present invention preferably has a large continuous pore. That is, the anti-DNA antibody is composed of immunoglobulins such as IgG and IgM (immunoglobulin M) and has a molecular weight of 16 to 9
Since it is a macromolecule of 100,000, it is necessary that the anti-DNA antibody can easily enter the porous body in order to adsorb it efficiently. There are various methods for measuring the pore diameter, and the mercury intrusion method is most often used, but it is difficult to apply the method to a hydrophilic porous body. An exclusion limit molecular weight is often used as a measure of the pore diameter in place of this, and a hydrophilic porous body,
It can be applied to any hydrophobic porous body. Exclusion limit molecular weight refers to the molecular weight of molecules that cannot enter (exclude) pores in gel permeation chromatography, as described in a compendium (eg, Hiroyuki Hatano and Toshihiko Hanai, Experimental High Performance Liquid Chromatography, Chemical Doujinshi). The molecular weight of the one with the smallest molecular weight. It is known that the exclusion limit molecular weight varies depending on the target compound. Generally, globular proteins, dextran, polyethylene glycol, and the like have been well examined, and globular proteins which are considered to be most similar to anti-DNA antibodies. It is appropriate to use the value obtained using (including virus). As a result of examination using various water-insoluble porous materials having different exclusion limits, unexpectedly, even those having an exclusion limit molecular weight of about 100,000, which is smaller than the molecular weight of the anti-DNA antibody, exhibit a certain level of adsorption ability, and Larger pore size does not mean higher capacity, but rather lower capacity and anti-DNA
It became clear that proteins other than antibodies were adsorbed, that is, there was an optimum range of pore diameter. In other words, when a water-insoluble porous material having an exclusion limit molecular weight of less than 100,000 is used, the amount of adsorption of the anti-DNA antibody is small and cannot be put to practical use. Even if a water-insoluble porous material having a molecular weight close to the above was used, an adsorbent which was practically usable to some extent was obtained. on the other hand,
As the exclusion limit molecular weight increases, the amount of adsorbed anti-DNA antibody increases, but eventually reaches a plateau. If the exclusion limit molecular weight exceeds 60 million, the surface area is too small, and the amount of adsorption is not only reduced remarkably, but also Anti-DNA
Adsorption of components other than antibodies, that is, non-specific adsorption increases,
The selectivity drops significantly. Therefore, the water-insoluble porous material used in the present invention has a preferred exclusion limit molecular weight of from 100,000 to 60,000,000, and more preferably from 400,000 to 60,000,000, more preferably from the viewpoint of a larger selective adsorption capacity. It is good to be 400,000 or more and 20,000,000 or less. Next, the porous structure of the water-insoluble porous body is preferably total porosity rather than surface porosity, and the pore volume is preferably 20% or more from the viewpoint of a large adsorption capacity. As the shape of the water-insoluble porous body, any shape such as a granular shape, a spherical shape, a fibrous shape, a membrane shape, and a hollow fiber shape can be selected. When a particulate water-insoluble porous material is used, the pressure loss is large when the particle size is less than 1 μm, and when the particle size is more than 5000 μm, the adsorption capacity is small, so that it is 1 μm or more and 5000 μm or less. Is preferred. The water-insoluble porous material used in the present invention may be either organic or inorganic.
Those which have little adsorption of body fluid components other than the antibody A (so-called non-specific adsorption) are preferable. The water-insoluble porous body is preferably hydrophilic rather than hydrophobic since hydrophilicity causes less nonspecific adsorption, and a water-insoluble porous body made of a compound having a hydroxyl group in the molecule is more preferable. Representative examples of the water-insoluble porous material used in the present invention include soft porous materials such as agarose, dextran and polyacrylamide, inorganic porous materials such as porous glass and porous silica gel, polymethyl methacrylate, and the like. Examples include, but are not limited to, porous polymer hardgels made from synthetic polymers such as polyvinyl alcohol and styrene-divinylbenzene copolymer and / or natural polymers such as cellulose. When the adsorbent used in the present invention is used for extracorporeal circulation treatment, it is necessary to flow an anti-viscous fluid such as blood or plasma at a high speed, so that hard water having sufficient mechanical strength which does not cause compaction is obtained. It is preferable to use an insoluble porous body. That is, the hard porous body is, as shown in Reference Examples described later, a water-insoluble porous body is uniformly packed in a cylindrical column, and the relationship between the pressure loss and the flow rate when the aqueous fluid flows is at least 0.3 kg. / Cm ² means a linear relationship. The sulfur used in the present invention has a molecular weight of 1,000 or more.
Oxidized polysaccharides have multiple sulfate groups in one molecule
A polysaccharide having a molecular weight of 1000 or more . [0022] Representative examples of the sulfated polysaccharide used in the present invention, heparin, dextran sulfate, chondroitin sulfate
Examples include, but are not limited to, acids . [0023] min <br/> molecular weight of 1000 or more sulfated polysaccharides that have been fixed to the adsorbent used in the present invention may be one, or may be two or more. [0024] used in the present invention the adsorbent refers to those water-insoluble porous material molecular weight 1000 or more sulfated polysaccharide is stationary. Sulfuric acid with a molecular weight of 1000 or more
There are various methods for introducing a polysaccharide into an adsorbent.
It may be introduced by a method. The representative introduction method of the anionic functional groups to sell a fixed state of the compound having an anionic functional group molecular weight of 1000 or more polyanionic compound having a or other anionic functional group (1) anionic A method of forming an adsorbent by polymerization using a compound containing a functional group or a functional group which can be easily converted to an anionic functional group as a monomer or a cross-linking agent; (2) forming a compound containing an anionic functional group on a water-insoluble porous material; (3) a method in which a compound having an anionic functional group is fixed to a water-insoluble porous body by directly reacting a compound forming an anionic functional group with the water-insoluble porous body. can give. Representative examples of monomers or cross-linking agents containing an anionic functional group or a functional group which can be easily converted to an anionic functional group used in the method (1) include acrylic acid and its ester, methacrylic acid and its Examples include, but are not limited to, esters and styrene sulfonic acids. The method (2), that is, the method of immobilizing a compound containing an anionic functional group on a water-insoluble porous material includes a method by physical adsorption, a method by ionic bonding, and a method by covalent bonding. Yes, any method may be used, but it is important that the anionic functional group-containing compound is not released during sterilization or during treatment in order to use the adsorbent for therapeutic purposes. The coupling method is preferred. When the compound having an anionic functional group is fixed by a covalent bond, it is preferable that the compound having an anionic functional group has a functional group other than the anionic functional group that can be used for fixing. Representative examples of the functional groups that can be used for immobilization include amino groups, amide groups, carboxyl groups, acid anhydride groups, succinylimide groups, hydroxyl groups, thiol groups, aldehyde groups, halogen groups, epoxy groups, silanol groups, and the like. But are not limited to these. There are a large number of anionic functional group-containing compounds having these functional groups. Taurine, sulfanilic acid, glycine, phosphorylethanolamine and the like which will be described later are examples. Representative examples of the compound containing a sulfate group among the compounds containing an anionic functional group include sulfates of hydroxyl group-containing compounds such as alcohols, saccharides and glycols. Partially sulphated esters of polyhydric alcohols, especially sulphated saccharides, contain both sulphate groups and functional groups required for immobilization, have high biocompatibility and high activity, and are easily sulphated polysaccharides. It is particularly preferable because it can be fixed to a water-insoluble porous body. Next, the compound having an anionic functional group is immobilized on the water-insoluble porous material by the method (3), ie, by reacting the compound forming an anionic functional group with the water-insoluble porous material. A typical example of a method for introducing an anionic functional group is a reaction for introducing a sulfate group into a hydroxyl group-containing porous body. In this case, a sulfate group can be directly introduced by reacting a hydroxyl group-containing water-insoluble porous material with a reagent such as chlorosulfonic acid or concentrated sulfuric acid. The amount of the introduced anionic functional group is preferably from 0.01 μmol to 10 mmol per 1 ml of the adsorbent. If it is less than 0.01 μmol, the adsorbing ability is not sufficient, and if it exceeds 10 mmol, non-specific adsorption becomes too large to make it practically practical. A more preferred anionic functional group introduction amount is 1 μmol or more and 100 μmo.
1 or less. There are various methods for removing an anti-DNA antibody from a body fluid using the adsorbent used in the present invention, and any method may be used. A container having an inlet and an outlet for a fluid, a fluid and the fluid Although the components can pass contained, on a water-insoluble porous material molecular weight 1000 or more hardness sulfate
A simple method is to pass a body fluid through a filter through which an adsorbent of an anti-DNA antibody formed by immobilizing a saccharide cannot pass, and a device for removing an anti-DNA antibody comprising the adsorbent of the anti-DNA antibody filled in the container. preferable. FIG. 1 is a schematic sectional view of an embodiment of the anti-DNA antibody removing apparatus of the present invention. In FIG. 1, (1) and (2) are the inlets and outlets of the respective fluids, (3) is the adsorbent of the present invention, (4) and (5) are the fluids and the components contained in the fluids. Is a filter or mesh through which the adsorbent used in the present invention cannot pass, (6) is a column, and (7) is a container. Here, the filter (4) on the fluid inlet side may not be present. Hereinafter, the removing apparatus of the present invention will be described in more detail by way of examples, but the present invention is not limited to only such examples. Reference Example Agarose gel (trade name: Biogel A5m, manufactured by Bio-Rad, particle size: 50 to 100 mesh) and a synthetic polymer were placed on a glass column (inner diameter: 9 mm, column length: 150 mm) equipped with a filter having a pore size of 15 μm at both ends. Gel (trade name: Toyopearl HW65, manufactured by Toyo Soda Kogyo Co., Ltd., particle size: 50 to 100 μm) and porous cellulose gel (trade name: Cellulofine GC-700, manufactured by Chisso Corporation, particle size: 45 to 100 μm) Each was uniformly filled, water was circulated through the column by a peristatic pump, and the relationship between the flow rate and the pressure loss ΔP was determined. The result is shown in FIG. As is clear from the figure, the agarose gel, which is a soft gel, consolidates above a certain flow rate, and the flow rate does not increase even if the pressure is increased, whereas the hard gels such as Toyopearl and Cellulofine increase the pressure. The flow rate increases almost in proportion to. Production Example 1 Cellulose CK-A3, a porous cellulose gel (trade name, manufactured by Chisso Corporation, exclusion limit molecular weight of globular protein of 5)
20 million, particle size 45-105 μm) 20% in 100 ml
NaOH 40 g, heptane 120 g and nonionic surfactant Tween 20 (trade name, Kao Atlas Co., Ltd.)
Was added in 10 drops. After stirring at 40 ° C. for 2 hours, epichlorohydrin (50 g) was added and the mixture was stirred for 2 hours, and the gel was washed with water and filtered to obtain an epoxidized cellulose gel (hereinafter, referred to as epoxidized gel). Comparative Production Example 1 A solution prepared by dissolving 0.17 g of sulfanilic acid in 10 ml of water and adjusting the pH to 9.9 was added to 5 ml of the epoxidized gel obtained in Production Example 1, and the mixture was shaken at room temperature for 24 hours. % Monoethanolamine aqueous solution was added and shaken to seal unreacted epoxy groups to obtain a cellulose gel in which sulfanilic acid was fixed. The amount of anionic functional groups introduced by the immobilized sulfanilic acid was 6.5 μm per ml of the adsorbent.
ol. Comparative Production Example 2 In 5 ml of the epoxidized gel obtained in Production Example 1, 0.1 g of phosphorylethanolamine was dissolved in 10 ml of water to adjust the pH.
Add the solution adjusted to 9.6, shake at 40 ° C. for 4 hours,
A 0.5% aqueous solution of monoethanolamine was added, and the mixture was shaken to seal unreacted epoxy groups to obtain a cellulose gel on which phosphorylethanolamine was fixed. The amount of the anionic functional group introduced by the immobilized phosphorylethanolamine was 4 μmol per 1 ml of the adsorbent. Production Example 1 5 ml of the epoxidized gel obtained in Production Example 1 had a molecular weight of about 500.
0, dextran sulfate sodium 15% sulfur content 4
g and 5 ml of water were added to adjust the pH to 9, and the mixture was adjusted to 16 at 45 ° C.
Shake for hours. After that, the gel was separated by filtration, washed with a 2M aqueous solution of sodium chloride, a 0.5M aqueous solution of saline and water in this order, added with a 0.5% aqueous solution of monoethanolamine and shaken to seal unreacted epoxy groups. Thus, a cellulose gel on which dextran sulfate sodium was fixed was obtained. The amount of anionic functional group introduced by the immobilized dextran sulfate was 10 μmol per 1 ml of the adsorbent. Comparative Production Example 3 To 5 ml of the epoxidized gel obtained in Production Example 1 was added glycine 0.1 g.
A solution adjusted to pH 9.8 by dissolving 22 g in 10 ml of water was added, shaken at room temperature for 24 hours, added with a 0.5% aqueous solution of monoethanolamine and shaken to seal unreacted epoxy groups. A cellulose gel with glycine immobilized was obtained. The amount of the anionic functional group introduced by the immobilized glycine was 9 μmol / ml of the adsorbent. Comparative Production Example 4 Taurine was added to 5 ml of the epoxidized gel obtained in Production Example 1.
A solution adjusted to pH 9.0 by dissolving 37 g in 10 ml of water was added, and the mixture was shaken at room temperature for 24 hours. A 0.5% aqueous solution of monoethanolamine was added and shaken to seal unreacted epoxy groups. Yielded a cellulose gel with immobilization. The amount of anionic functional group introduced by the immobilized taurine was 5 μmol / ml of the adsorbent. Comparative Production Example 5 10 ml of cellulose CK-A3 was washed with water and filtered by suction.
6 ml of dimethyl sulfoxide, 2N-NaOH
2.6 ml and 1.5 ml of epichlorohydrin were added to give 4
Stirred at 0 ° C. for 2 hours. After the reaction, the gel was separated by filtration and washed with water to obtain a cellulose gel into which an epoxy group was introduced. 6 ml of concentrated aqueous ammonia was added thereto, and
The reaction was carried out at 2 ° C. for 2 hours to obtain an aminated cellulose gel. A solution prepared by dissolving 0.2 g of sodium polyacrylate having a molecular weight of 190,000 to 500,000 in 10 ml of water and adjusting the pH to 4.5 was added to 5 ml of the gel, and 1-ethyl-3- (dimethylaminopropyl) was further added. ) Add 200 mg of carbodiimide while maintaining pH 4.5, and add
Shake for 4 hours. After the reaction, the gel was separated by filtration and washed with water to obtain a cellulose gel into which polyacrylic acid had been introduced. The amount of anionic functional group introduced by the immobilized polyacrylic acid was 14 μmol per 1 ml of the adsorbent. Example 2 A porous cellulose gel was prepared using cellulose CK-A22 (trade name, manufactured by Chisso Corp., molecular weight cutoff of globular protein of 20).
Million, particle size 45-105 μm, crosslinked gel), Cellulofine GCL-2000 (trade name, manufactured by Chisso Corporation), molecular weight cutoff of globular protein of 3,000,000, particle size 45-105
μm, crosslinked gel), Cellulofine GC-700 (trade name, manufactured by Chisso Corp., exclusion limit molecular weight of globular protein 40)
10,000, particle size 45-105 μm), Cellulofine GC-2
00m (trade name, manufactured by Chisso Corporation, molecular weight exclusion limit of globular protein of 120,000, particle size of 45 to 105 μm), Cellulofine GCL-90 (trade name, manufactured by Chisso Corporation, molecular weight of exclusion limit of globular protein 3. (50,000, particle size 45-105 μm)
Except for the change, a cellulose gel in which dextran sodium sulfate was fixed was obtained in the same manner as in Production Example 1 and Example 1. The amounts of anionic functional groups introduced by the immobilized dextran sulfate were 16, 18, 24, 30, and 37 μmol per 1 ml of the adsorbent, respectively. Example 3 Epoxy Activated Sepharose CL-6B (trade name, manufactured by Pharmacia Fine Chemicals, exclusion limit molecular weight of globular protein of 4,000,000, particle size of 45 to 165 μm), which is an epoxidized crosslinked agarose gel, was used. Otherwise, dextran sulfate sodium was immobilized in the same manner as in Example 1. The amount of anionic functional group introduced by the immobilized dextran sulfate was 20 μmol per 1 ml of the adsorbent. Production Example 4 Hydrogel FP-HG which is a hydrophilic porous hard hydrogel containing polymethyl methacrylate as a main component (trade name, manufactured by Mitsubishi Kasei Corporation, exclusion limit molecular weight of spherical protein of 400)
A gel with dextran sulfate fixed thereon was obtained in the same manner as in Production Example 1 and Example Production Example 1 except that the particle size was 120 μm. The amount of anionic functional groups introduced by the immobilized dextran sulfate was 9 μmo per ml of adsorbent.
l. Example 5 Comparison In 2 g of aminated cellulose gel obtained in the same manner as in Production Example 5 , 4 g of dextran sodium sulfate having a molecular weight of 5,000 and a sulfur content of 15% was dissolved in 8 ml of 0.1 M phosphate buffer (pH 8.0). The solution was added and shaken at room temperature for 16 hours. After the reaction, 20 mg of NaCNBH ₃ was added, and the mixture was stirred at room temperature for 30 minutes. After heating at 40 ° C. for 4 hours, the gel was separated by filtration and washed with water to obtain a cellulose gel in which dextran sulfate was fixed. The amount of anionic functional groups introduced by the immobilized dextran sulfate was 18 μmol / ml of adsorbent.
l. Experimental Example 1 Each of the adsorbents obtained in Examples 1 and 5 and Comparative Examples 1 to 5 was mixed with 1 ml of a polypropylene mini column (inner diameter:
7 mm), washed with physiological saline, passed through 0.1 ml of serum containing anti-dsDNA antibody diluted 10-fold with physiological saline, and further 5 ml of 0.15 M Tris-HCl buffer, After washing at pH 7.6, the antibody titer of the surviving fraction was measured by the enzyme-linked immunosorbent assay (ELISA). The anti-dsDNA antibody titer is determined by dropping a diluted sample onto a plate to which DNA is attached, performing an antigen-antibody reaction, dropping a peroxidase-labeled anti-human immunoglobulin antibody, and measuring the enzyme color reaction by SLT-210 (trade name, Lab Science) (Manufactured by K.K.). Table 1 shows the names of compounds having an anionic functional group immobilized on each adsorbent and the relative antibody titer in percentage of the antibody titer in the slip-through fraction relative to the antibody titer of the original serum of each adsorbent. The anti-dsDNA antibody binding activity in Table 1 or La Defense dextran adsorbent sodium sulfate is fixed it can be seen that excellent especially. Experimental Example 2 The relative antibody titer was determined in the same manner as in Experimental Example 1 except that the adsorbents obtained in Production Examples 1 to 4 were used. Table 2 shows the names of various water-insoluble porous bodies using the results. As can be seen from Table 2, cellulose GC-200m having an exclusion limit molecular weight smaller than the molecular weight of the anti-DNA antibody of about 160,000.
Also, it can be seen that the anti-dsDNA antibody binding ability of cellulose GCL-90 is slightly lower. Experimental Example 3 The same procedure as in Experimental Example 1 was carried out except that the adsorbents obtained in Examples 1 and 5 and Comparative Examples 1 to 5 were used, and serum from an SLE patient having a high anti-ssDNA antibody titer was used. The relative antis
The sDNA antibody titer was determined. The results are shown in Table 3 together with the names of the anionic functional group-containing compounds fixed on each adsorbent. Table 3 shows that the adsorbent on which dextran sulfate sodium was immobilized had excellent anti-ssDNA antibody binding ability. [Table 1] [Table 2] [Table 3] The removal apparatus of the present invention has the effect of selectively removing anti-DNA antibodies from body fluids.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic cross-sectional view of one embodiment of the anti-DNA antibody removing device of the present invention. FIG. 2 is a graph showing the results of examining the relationship between flow rate and pressure loss using three types of gels. [Description of Signs] 1 Inlet 2 Outlet 3 Adsorbent 4, 5 Filter 7 Container

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-54-15379 (JP, A) JP-A-58-61752 (JP, A) JP-A-59-186558 (JP, A) JP-A-62 191041 (JP, A) (58) Field surveyed (Int. Cl. ⁷ , DB name) A61M 1/36 543 B01D 15/08 B01J 20/26 G01N 33/564 A61K 39/395

Claims (1)

(57) Claims: container having an inlet and an outlet of the first fluid, but components contained in the fluid and the fluid can pass, the water-insoluble porous material in molecular weight of 1,000 or more sulfated polysaccharides A filter through which the adsorbent of the anti-DNA antibody in which is immobilized cannot pass;
And a device for removing an anti-DNA antibody comprising an anti-DNA antibody adsorbent filled in the container. 2. Exclusion limit molecular weight of globular protein in water-insoluble porous material
400,000 over 60 million less der Ru patent remover ranging first claim of claim. 3. The removal device according to claim 1, wherein the water-insoluble porous body is made of a compound having a hydroxyl group.