JPH0226988B2 - - Google Patents

Description

BACKGROUND OF THE INVENTION (Technical Field) The present invention relates to a body fluid component separation material that adsorbs and separates specific components from body fluids such as blood, and a body fluid component separation device using the same. (Prior Art and its Problems) In recent years, plasma exchange therapy has been used as a treatment for diseases in which specific components in body fluids cause serious symptoms. This therapy is particularly effective in cases where dialysis of the pathogenic substance is difficult, such as myasthenia gravis, rheumatoid arthritis,
It is applied to autoimmune diseases such as lupus erythematosus, immune-related diseases such as glomerulonephritis, bronchial asthma, and polyneuritis, rejection reactions associated with organ transplants, liver failure, hypertension, cancer diseases, and others. Among these, autoimmune diseases are diseases caused by humoral or cellular immune responses against antigens in one's own cells and tissues, and antibodies against the self formed as a result of this. . However, since plasma exchange therapy indiscriminately removes all plasma components, there is a problem in that useful components of plasma are also lost in addition to pathogenic substances. In addition, many problems have been pointed out, such as a shortage of plasma and plasma preparations as replacement fluids, and complications such as serum hepatitis and allergies. Circulating fluid purification therapy is considered desirable. In this case, it is necessary to sufficiently and selectively remove pathogenic substances from one's own blood to achieve the therapeutic objective and prevent hypoproteinemia. Conventionally, the following adsorbents have been known as purification materials for this purpose. It is being - Porous resins (e.g. "Amberlite XAD-7" manufactured by Ro¨hm & Haas, etc.) - Ion exchangers (e.g. carboxymethylcellulose, diethylaminoethyl agarose, etc.) - Inorganic porous bodies (e.g. porous gallus, ceramics, etc.) - Affinity adsorbent However, porous resins and ion exchangers have low adsorption capacity and low adsorption specificity, so they also adsorb albumin in body fluids.As a result, when applied as a blood purification material in the above therapy, it has a therapeutic effect. There are safety issues, such as not only insufficient osmotic pressure but also edema due to abnormal osmotic pressure characteristic of hypoproteinemia.In addition, inorganic porous materials have relatively good adsorption capacity and adsorption properties. However, it is still insufficient for practical use.In contrast, affinity adsorbents have excellent adsorption capacity and adsorption specificity, and are considered promising as blood purification materials.This type of adsorbent Based on the difference in adsorption action, they are classified into biological affinity adsorbents and physicochemical affinity adsorbents, and their general characteristics and problems are explained as follows.First, biological affinity adsorbents binds to and adsorbs pathogenic substances in the blood through biological interactions such as antigen-antibody binding, complement binding, and Fc binding, and has extremely excellent adsorption specificity.Moreover,
Most of these use bioactive polymers such as DNA, anti-LDL antibodies, and protein A as ligands (substances that have an affinity for the target pathogenic substance), so there is a problem that raw materials are expensive and difficult to secure. In addition, because the stability of the ligand is poor, the manufacturing, sterilization, storage, transportation, and
Difficult to maintain activity during storage. In addition, since the ligand is essentially a physiologically active substance, it must be taken into account that when it comes into contact with blood, it not only exhibits the desired affinity but also exhibits its original physiological action and causes side effects. It won't happen.
Moreover, since the ligand is a foreign protein, if it is released and eluted from the adsorbent carrier, side effects will occur due to its antigenicity. On the other hand, physicochemical affinity adsorbents bind to pathogenic substances in blood through physical or chemical interactions such as electrostatic bonds and hydrophobic bonds, and adsorb and separate the substances to remove them. As the ligand in this case, synthetic compounds such as polylysine, methylated albumin, tryptophan, and phenylalanine can be used. Therefore, it has the advantage of being able to be manufactured in large quantities, being relatively inexpensive, and having stable activity. In addition, since many of them are generally excellent in safety when they come into contact with blood, they are most promising as purifying materials for use in extracorporeal circulation body fluid purification therapy for treating the above-mentioned diseases. Furthermore, due to its action and price, it is useful not only as a blood purification material for the above-mentioned therapies, but also for the separation and purification of specific components of body fluids such as immunoglobulins, immune complexes, and immune-related soluble factors, or for the testing of these components. Expected uses. Conventionally known adsorbents belonging to this category are as follows. Porous materials having carboxyl groups or sulfonic acid groups on the surface (JP-A-147710, JP-A No. 56-1477-
56038, 57-75141, 57-170263, 57-
197294) Hydrophilic carrier to which hydrophobic amino acids are bound (JP-A No. 57-122875, No. 58-15924, No. 58-
165859, 58-165861) Hydrophilic carrier bound to modified immunoglobulin (lgG)
77625, 57-156035) Porous body to which methylated albumin is bound (JP-A-55-120875, 55-125872) Hydrophilic carrier to which sugar is bound (JP-A-57-120875, 55-125872)
134164, 58-133257) Porous bodies bound with purine bases, pyrimidine bases, or sugar phosphoric acids (Japanese Patent Laid-open No. 1983-134-134164, 58-133257)
192560, 58-61752, 58-98142) However, these conventional physicochemical affinity adsorbents are still not sufficient for the treatment of autoimmune diseases, etc. by extracorporeal circulating fluid purification therapy, and even higher efficiency is needed. There is a need for a purifying material that can remove pathogenic substances with specificity and has less negative effects on body fluids. Purpose of the Invention The present invention has been made in view of the above circumstances, and its purpose is to be able to adsorb and separate specific components contained in body fluids such as blood, lymph fluid, ascites, etc. with high efficiency and high specificity, and to have stable activity. It is an object of the present invention to provide a body fluid component separation material that is easy to sterilize and store, and a body fluid component separation device using the same. The body fluid component separation material which is the first object of the present invention is
Among the acrylic polymers obtained by polymerizing a monomer mixture containing an unsaturated radically polymerizable monomer having an oxirane group and a crosslinkable monomer, the oxirane group content is 0.1 to 10 mmol per 1 g of dry weight.
It is obtained by bonding a heterocyclic compound to oxirane-acrylic beads. At this time, atoms other than the heterocycle of the heterocyclic compound are covalently bonded to one carbon constituting the oxirane group exposed on the surface of the oxirane-acrylic beads, and the oxirane group is ring-closed, and the oxygen atom is It will be covalently bonded to the other carbon atom as a hydroxyl group. A body fluid component separation device, which is the second object of the present invention, can be obtained by filling the above body fluid component separation material into a container having a body fluid inlet and a body fluid outlet that communicate with each other. Add elements such as body fluid circulation pumps as necessary. The present invention can be particularly suitably used in extracorporeal circulation body fluid purification therapy aimed at treating autoimmune diseases and the like. DETAILED DESCRIPTION OF THE INVENTION The body fluid component separation material of the present invention belongs to the physicochemical affinity adsorbent described above. The targeted substance to be adsorbed is protein in body fluids, and a more detailed explanation is as follows. That is, normal immunoglobulins (A, D, E, G, M), various autoantibodies, complexes between immunoglobulins or between immunoglobulins and other substances (especially antibodies), complement, fibrinogen, soluble fibrin, Low-density lipoprotein, cancer cell growth factor, immune-related soluble factor (IRA: lmmuno-regulatory α-globulin)
T-cell growth factor (TCGF)
factor), GSF (Growth soluble factor), SSF
(Suppresor soluble factor), TRF (T-cell
replacing factor), KHF (Killer cell helper)
factor), LSF (Lymphocyte-stimulating factor), LSF (Lymphocyte-stimulating factor)
factor), CIF (Competence-inducing factor),
TDF (Thymocyto-differentiation factor),
Interleukins, etc. Among these, examples of autoantibodies include cell surface antibodies, gastric parietal cell microsomal antibodies, organ-specific (group) antibodies such as adrenal cortical adrenocortical antibodies, antibodies against acetylcholine receptors, red blood cell antibodies, Hirasu smooth muscle antibodies, and autoantibodies. Intermediate type (group) such as urin receptor antibodies, DNA antibodies,
Organ-nonspecific types (group 3) include coagulation factor antibodies, anti-nuclear antibodies, and anti-LGG antibodies. All of these pathogenic protein substances to be separated in the present invention are contained in the globulin fraction of the body fluid protein fractions. The body fluid component separation material of the present invention uses oxirane-acrylic beads as an insoluble carrier, and a heterocyclic compound is bonded to the surface of the insoluble carrier. Therefore, the insoluble carrier, the heterocyclic compound, the bonding method thereof, etc. will be explained respectively. Oxirane-acrylic beads used as insoluble carriers are obtained by copolymerization of glycidyl methacrylate or allyl glycidyl ether, methacrylamide, methylene-bis-methacrylamide. The manufacturing method is Ro¨hm
Pharma) (UK patent no.
1329062, German Patent Publication No. 2237316, German Patent Publication No. 2263289). Among these oxirane-acrylic beads, those that are particularly preferably used as the insoluble carrier in the present invention have a crosslinking monomer content of 5% by weight or more and a radically polymerizable monomer having an oxirane group content of 5 to 60% by weight. It was obtained from a monomer mixture. Examples of such particularly preferred oxirane-acrylic beads include those provided by Rohm Pharma under the trade name "Eupergit C". This is imported and sold domestically by Higuchi Shokai. The shape of the oxirane-acrylic beads is spherical so that they do not damage cells and are less likely to break or chip. The average particle diameter used is in the range of 0.05 mm to 5 mm, preferably in the range of 0.1 mm to 0.2 mm, taking into account the flow rate and circulation pressure of body fluids. To determine the average particle size, after classifying using a sieve specified in JIS-Z-8801, for each class, the intermediate value between the upper limit particle size and the lower limit particle size is taken as the particle size of the class, and the weight of these particles is calculated. Calculate the overall average particle size as an average. The oxirane-acrylic beads are preferably porous with a large surface area in order to adsorb and remove pathogenic substances with high efficiency. Furthermore, if the average pore diameter of the porous body is too small, the amount of the pathogenic substance adsorbed will be small, and if it is too large, the strength and surface area of the porous body will decrease, so either case is not practical. From this point of view, the preferred average pore diameter is 100Å~
In the range of 5000 Å, more preferably from 200 Å
It is in the range of 3000 Å. The average pore diameter is preferably measured using a mercury intrusion porosimeter. In this method, mercury is injected into a porous body, and the amount of pores is determined from the amount of mercury that has entered, and the pore diameter is determined from the pressure required for injecting. Oxirane-acrylic beads have oxirane groups on their surface. As described below, this oxirane group has the ability to immobilize a heterocyclic compound on the bead surface. The content of oxirane groups in oxirane-acrylic beads was determined by the thiosulfate method (R.Axen, as quoted by L-
Sundberg and J―Porath in J,
A range of 800 to 1000 μmol/g-dry is desirable when measured by Chromatography, 90 (1974), 89). Next, the heterocyclic compound bonded to the oxirane-acrylic beads will be explained. A heterocyclic compound is an organic compound containing a carbon atom and a heteroatom such as nitrogen, oxygen, or sulfur in the ring, and the heterocycle is often a 5-membered ring or a 6-membered ring. Examples are as follows. Namely, furan and its derivatives, thiifene and its derivatives and dithiolane derivatives, pyrrole and its derivatives, azoles,
Pyridine and its derivatives, quinoline and its related compounds, acridine and its related compounds, pyridine and its related compounds, pyrazine and its related compounds, pyran and pyrone and their related compounds, phenoxazine, phenothiazine, pterin and alloxazine compounds, purine bases, nucleic acids , hemin, chlorophyll, vitamin B ₁₂ , phthalocyanine, alkaloids, fused ring heterocyclic compounds, etc. Among these many heterocyclic compounds, sulfonamides (limited to those having a heterocycle) known as sulfur agents, derivatives thereof, and luminol give preferable results. Among the sulfur drugs, sulfathiazole gives favorable results. The above heterocyclic compound is bonded to the oxirane groups present on the surface of the oxirane-acrylic beads. The bond forming position between the two is between an atom other than the heterocycle of the heterocyclic compound and one carbon atom constituting the oxirane group, and the form thereof is a covalent bond. The formation of this bond involves ring opening of oxirane, and the oxygen atoms forming the oxirane group become hydroxyl groups and bond. FIG. 1 shows the surface of "Eupergit C" to which sulfathiazole was bonded as described above. The part surrounded by the broken line in the figure shows the ring-opened oxirane group, and in this case, the aniline nitrogen of sulfathiazole is bonded to the oxirane carbon as shown in the figure. The above bond-forming reactions involving ring-opening of oxirane groups are relatively easy. In particular, when the heterocyclic compound contains a hydroxyl group, an amino group, a thiol group, or a carbonyl group, it is possible to react in a wide pH range, and bonds can be formed between these nitrogen or oxygen atoms and the oxirane carbon atom. can be caused. Moreover, the reaction in this case takes place at room temperature (21~
The reaction is completed in 16 to 72 hours at 25°C), but the reaction rate can be further accelerated by using a catalyst such as boron trifluoride etherate, sodium phenol, triethylamine, or pyridine. Next, the body fluid component separating material of the present invention obtained as described above will be explained. One of its characteristics is that the oxirane-acrylic beads used as an insoluble carrier and the heterocyclic compound used as a ligand are firmly bonded via a covalent bond as described above. In addition to covalent bonding, other methods for immobilizing a ligand on the surface of an insoluble carrier include ionic bonding, physical adsorption, embedding, and insolubilization by precipitation on the carrier surface. The ligand is easily detached from body fluids and lacks stability. For this reason, when used in extracorporeal circulation body fluid purification therapy, for example, serious problems arise such as the ligand getting mixed into the blood and causing side effects. On the other hand, in the body fluid component separating material of the present invention, such a problem does not occur because the ligand is firmly bound to the insoluble carrier and is stable as described above. The most significant feature of the body fluid component separation material according to the present invention is that it has a highly efficient and highly specific adsorption capacity for the separation material mentioned above, as shown in the results of the examples described below. It is in. This characteristic was obtained not only by the contribution of the heterocyclic compound used as the ligand but also by the combination of the contribution by the oxirane-acrylic beads used as the carrier. In general, adsorbents composed only of hydrophobic compounds, i.e. adsorbents with strong hydrophobic binding, have many useful proteins other than those to be removed, such as albumin fractions in body fluids, so they can selectively remove pathogenic substances. Not suitable for On the other hand, adsorbents made of hydrophilic compounds with strong hydrogen bonds or compounds with many charged groups with strong electrostatic bonds cannot adsorb pathogenic substances because the amount of protein attached is extremely low. Therefore, in order to separate pathogenic substances in body fluids, an adsorbent that has an appropriate combination of various interaction forces is suitable. If the body fluid component separation material of the present invention is examined from this point of view, it will be as follows. First, the heteroatom (first
In the illustrated example, the nitrogen atom and sulfur atom of the thiazole ring have a lone pair of electrons in the outermost orbital, which acts as a proton acceptor, and a heterocycle with few dissociable groups exhibits hydrophobicity. Among the heterocyclic compounds, the sulfonamide moiety of the sulfur agent and the carbonyl group and imino group of luminol have hydrogen bonding properties. On the other hand, acrylic beads bonded with a heterocyclic compound have a methyl group exhibiting hydrophobicity and an acid amide group exhibiting hydrogen bonding properties on the surface of the polymeric carbon chain. Furthermore, the hydroxyl group formed by ring opening of the oxirane group exhibits hydrophilicity. Due to these elements, the separation material of the present invention causes a combination of hydrophobic bonds, electrostatic bonds, and hydrogen bonds to interact with the amino acid residues of the pathogenic substance, and the heterocyclic compound moiety It is interpreted that favorable results were obtained because the molecule of the disease-causing substance was appropriately embedded in the molecules. Next, the body fluid component separation device of the present invention will be explained. As described above, the separation device of the present invention has the body fluid component separating material filled and held in a container having a body fluid inlet and an outlet. Container materials include glass, stainless steel, polyethylene,
Although polypropylene, polycarbonate, polystyrene, polymethyl methacrylate, etc. can be used, polypropylene, polycarbonate, etc., which can be autoclaved and are easy to handle, are particularly preferred. Further, it is preferable that a filter is provided between the entrance and exit portion of the container body and the separation material layer, which has a mesh that allows body fluid to pass through but prevents the separation material from passing through.
The filter may be made of any material as long as it is physiologically inert and has high strength, but polyester and polyamide are particularly preferably used. FIG. 2 is a sectional view showing an embodiment of the body fluid component separation device according to the present invention. The body fluid is introduced through the inlet 4 and adsorbed by the body fluid component separating material 2, and then led out through the outlet 5. The separation material is held within the column by filters 3, 3'. When applying the device of the present invention to extracorporeal circulation body fluid purification therapy, there are two methods. The first is
This is a method in which blood taken from the body is separated into plasma components and blood cell components, only the plasma component is purified using the separation device, and then returned to the body together with the blood cell components. In this case, a centrifuge or a membrane or hollow fiber plasma separator is used for blood cell/plasma separation. The second method is to purify blood taken from the body by passing it directly through the device. Among these methods, an example applied to the former method is shown in FIG. In this case, blood is introduced from the blood inlet 6 and supplied to the plasma separation device 8 through the pump 7, where it is separated into blood cells and plasma. The separated plasma is supplied to the body fluid component separation device 1 according to the present invention through the pump 7', and after being adsorbed, the plasma/plasma/
The blood cells are mixed with the blood cell mixer 9 and then sent to the blood outlet port 1.
Derived from 0. Note that the method for circulating body fluids may be carried out continuously or intermittently depending on clinical needs and equipment conditions. Hereinafter, it will be explained in more detail according to Examples. Example 1 First, carbonate buffer (PH
10) and dimethylformamide (volume ratio 2:3), sulfathiazole was dissolved at a concentration of 0.1 mol/ml. Oxirane-acrylic beads (“Eupergit C” manufactured by Ro¨hm Pharma) were added to the solution; the ratio of crosslinking monomer was 30%.
% by weight) at a rate of 0.1 to 0.2 g/ml, and after degassing, tri-n-butylamine and 1.0 ml of pyridine were added as catalysts. This was heated in a water bath at 80° C. for 1 hour, and then stirred overnight at room temperature using a Blood Mixer (Model BM-101, manufactured by Kayagaki Irika Kogyo). Next, in order to remove unreacted oxirane groups, 100 ml of an ethanolamine solution with a concentration of 1 mol/(PH8) was added, and the mixture was stirred overnight.
Thereafter, it was washed successively with distilled water, an acetic acid buffer solution containing 0.5 mol of sodium chloride at a concentration of 0.02 mol/(PH4), and a carbonate buffer solution at a concentration of 0.2 mol/(PH10). It is presumed that in the thus obtained adsorbent beads, the aniline nitrogen of sulfathiazole was bonded to the oxirane group of "Euperchyd C" by ring-opening, as shown in FIG. 3 g of the adsorbent beads obtained above were weighed into a glass test tube ("Larbo" manufactured by Terumo Corporation) and subjected to the following adsorption experiment. For adsorption experiments, first add 3 ml of phosphate buffer solution (PBS) containing 137 mmol of sodium chloride and 2.6 mmol of potassium chloride at a concentration of 8 mmol (PH7.2) to the test tube containing the above-mentioned adsorbent, and use an aspirator (manufactured by Tokyo Rikakiki). "A-2S") was degassed. Next, bovine plasma 3 was supplemented with 6 IU/ml of heparin as an anticoagulant and 50 μl/ml of ACD-A solution.
ml was added, and adsorption treatment was carried out by incubating for 90 minutes in a hot air circulation constant temperature bath at 37° C. while stirring using a blood mixer. Thereafter, the adsorbed amounts of albumin (Alb.), globulin (Glob.), and immunoglobulin G (IgG) were measured by the following method. That is, the contents of the test tube were transferred using 1 ml of PBS into a minicolumn prepared using a disposable syringe manufactured by Terumo Corporation with a capacity of 5 ml, and the column was washed with 5 ml of PBS and the effluent was collected. . After measuring the volume of the effluent, the amount of Alb. and total protein (Prot.) contained in it was determined.
They were measured using the bromcresol green (BCG) method and the Biuret method, respectively. Also, the Glob. amount is the Prot. amount
It was calculated as the difference from the amount of Alb. That is, for convenience, fibrinogen was also included in Glob. in the calculation. Separately, perform the same operation as above without using an adsorbent, and calculate the amount of adsorption by subtracting the amounts of Alb. and Glob. obtained for the effluent in that case from the respective values above. The respective adsorption rates were calculated by dividing the above values by these values. In addition, the amount of IgG in the effluent was measured by single radial immunodiffusion (SRID), and the same procedure as above was carried out.
The adsorption amount and adsorption rate of IgG were determined. The results of the above adsorption experiment are shown in Table 1. Example 2 An adsorbent was prepared in the same manner as in Example 1 except that a luminol solution with a concentration of 0.1 mmol/m was used instead of the sulfathiazole solution used in Example 1. An adsorption experiment similar to that in Example 1 was conducted using the obtained adsorbent. The results are shown in Table 1. Example 3 Instead of "Eupergit C" used in Example 1 (30% by weight of crosslinking monomer), the proportion of crosslinking monomer (N,N'-methylene-bis-acrylamide) was 5% by weight. Oxirane-acrylic beads polymerized from a monomer mixture were used. An adsorbent was prepared in the same manner as in Example 1 except for this. Table 1 shows the results of an adsorption experiment similar to that in Example 1 using 1 g of the obtained adsorbent. Example 4 The same procedure as in Example 3 was carried out except that luminol was used in place of sulfathiazole. Table 1 shows the results of the same adsorption test as in Example 1 using the obtained adsorbent. Comparative Example 1 An adsorbent was prepared in the same manner as in Example 1 except that a phenylalanine solution with a concentration of 0.1 mmol/mole was used in place of the sulfathiazole solution used in Example 1. An adsorption experiment similar to that in Example 1 was conducted using the obtained adsorbent. The results are shown in Table 1. Comparative Examples 2 to 4 In these comparative examples, N-hydroxysuccinimide active ester-agarose beads (“Affi-Gel-10” manufactured by Bio-Rad) were used instead of the oxirane-acrylic beads used in Example 1. Using. Further, in Comparative Example 2, as in Example 1, a sulfathiazole solution with a concentration of 0.1 mmol/m was used, and an adsorbent was prepared in the same manner as in Example 1 except for that. In Comparative Example 3, an adsorbent was prepared in exactly the same manner as in Example 1, except that a luminol solution with a concentration of 0.1 mmol/m was used instead of the sulfathiazole solution used in Example 1. In Comparative Example 4, an adsorbent was prepared in exactly the same manner as in Example 1, except that a phenylalanine solution with a concentration of 0.1 mmol/m was used instead of the sulfathiazole solution used in Example 1. Table 1 shows the results of adsorption experiments similar to those in Example 1 using the respective adsorbents obtained in Comparative Examples 2 to 4 above. Comparative Examples 5 to 8 In these comparative examples, oxirane-polystyrene beads (“EX-438” manufactured by Mitsubishi Kasei Corporation) were used instead of the oxirane-acrylic beads used in Example 1.
was used. Further, as the heterocyclic compound, sulfathiazole was used in Comparative Example 5, sulfamethiazole was used in Comparative Example 6, sulfasomezole was used in Comparative Example 7, and luminol was used in Comparative Example 8. Other than that, the same procedure as in Example 1 was carried out. Table 1 shows the results of adsorption experiments on the obtained adsorbent. Comparative Example 9 Polyacrylamide beads produced by copolymerization of acrylamide and N,N′-methylene-bis-acrylamide (“Bio-Rad”)
―Gel P-300''; Particle size when swollen: 100-200 mesh;
A molecular weight fractionation range of 60,000 to 400,000, 30 ml/g-dry) was used as an insoluble carrier. The amide group of the side chain of the polyacrylamide beads was converted into a carboxyl group by deamidation with a carbon salt, and then the following heterocyclic compound was bonded to this carboxyl group by dehydration condensation. At that time, 1-cyclohexyl-3-(2-
Morpholinoethyl) carbodiimide p-toluenesulfonate was used as the dehydration condensation agent. Sulfathiazole (Comparative Example 9) Luminol (Comparative Example 10) Phenylalanine (Comparative Example 11) Regarding the adsorbents obtained above, Example 1
The same adsorption experiment was conducted as in the case of , and the results shown in Table 1 were obtained.

【table】

[Table] Specific Effects of the Invention As is clear from the adsorption experiment results in the above Examples and Comparative Examples, the body fluid component separation material of the present invention can absorb pathogenic substances such as immunoglobulin, immune complexes, and immune-related soluble factors. It is possible to adsorb and remove proteins efficiently and with high selectivity. Furthermore, since the ligand is a low-molecular synthetic organic compound, sterilization can be performed easily and reliably. Furthermore, its constituent components, oxirane-acrylic beads and heterocyclic compounds, have low toxicity and are highly safe. That is, the LD ₅₀ value of oxirane-acrylic beads is
15 g/Kg, and among heterocyclic compounds, the LD ₅₀ value of sulfazole is 990 mg/Kg intravenously in mice. Due to these characteristics, the body fluid component separation material of the present invention is extremely suitable for adsorbing and removing pathogenic substances in body fluids and purifying body fluids, and is suitable for the treatment of autoimmune diseases, immune-related diseases, etc. by extracorporeal circulation body fluid purification therapy. effective. Furthermore, it can be effectively used not only for the above-mentioned therapeutic purposes, but also for the separation and purification of proteins such as immunoglobulins, immune complexes, and immune-related soluble factors, or for the testing of these substances. On the other hand, since the body fluid component separation device of the present invention has a simple structure, it can be used to easily separate and purify pathogenic substances using the body fluid component separation material, or to treat various diseases by purifying body fluids. Can be done.

[Brief explanation of drawings]

FIG. 1 is an explanatory diagram showing a state in which sulfathiazole is bonded to the surface of oxirane-acrylic beads, FIG. 2 is a cross-sectional view showing an embodiment of the body fluid component separation device according to the present invention, and FIG. This is a flowchart showing an example of extracorporeal circulation body fluid purification therapy using. 1... Body fluid component separation device, 2... Body fluid component separation material,
3, 3'... Filter, 4... Body fluid inlet, 5... Body fluid outlet, 6... Blood inlet, 7, 7'... Pump,
8...Plasma separation device, 9...Plasma/blood cell mixing device, 1
0...Blood outlet.

Claims (1)

[Scope of Claims] 1. Among acrylic polymers obtained by polymerizing a monomer mixture containing an unsaturated radically polymerizable monomer having an oxirane group and a crosslinkable monomer,
Oxirane group content is 0.1 to 1 g dry weight
A body fluid component separation material in which a heterocyclic compound is bonded to 10 mmol of oxirane-acrylic beads, wherein atoms other than the heterocycle of the heterocyclic compound constitute oxirane groups exposed on the surface of the oxirane-acrylic beads. A body fluid component separating material characterized in that the oxirane group is bonded to one carbon atom, and the oxirane group is ring-opened so that its oxygen atom is bonded to the other carbon atom as a hydroxyl group. 2. The body fluid component separating material according to claim 1, wherein the unsaturated radically polymerizable monomer having an oxirane group is 5 to 60% by weight, and the crosslinking monomer is 5% by weight or more. 3. The body fluid component separating material according to claim 1 or 2, wherein the heterocyclic compound is selected from the group consisting of sulfur drugs or derivatives thereof, and luminol. 4 Among acrylic polymers obtained by polymerizing a monomer mixture containing an unsaturated radically polymerizable monomer having an oxirane group and a crosslinkable monomer,
Oxirane group content is 0.1 to 1 g dry weight
A body fluid component separation material in which a heterocyclic compound is bonded to 10 mmol of oxirane-acrylic beads, wherein atoms other than the heterocycle of the heterocyclic compound constitute oxirane groups exposed on the surface of the oxirane-acrylic beads. A body fluid component separation material in which the oxirane group is ring-opened and its oxygen atom is bonded to the other carbon atom as a hydroxyl group is placed in a container having a liquid inlet and a liquid outlet. A body fluid component separation device characterized by being housed.