JPS62112562A - Material and apparatus for adsorbing rheumatoid factor - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention (1) Background of the Invention [Technical Field] The present invention relates to a novel rheumatoid factor adsorbent and a rheumatoid factor adsorption device using the adsorbent.

Plasma exchange is known to be effective in treating rheumatic diseases, but it is difficult to administer 1'4 of the fresh frozen plasma required for plasma exchange, and there is also a risk of hepatitis. be.

Therefore, treatment methods are being developed that selectively remove rheumatoid factors from autologous plasma and use the purified autologous plasma for reprinting. The rheumatoid factor adsorbent of the present invention is used in such treatment methods.

[Prior Art and Problems] All conventional rheumatoid factor adsorbents have been used in which a substance 'c1 (ligand) that specifically binds to rheumatoid factor is immobilized on a water-insoluble carrier. Such adsorbents require a step to immobilize the ligand on the 114 body,
Another disadvantage is that the ligand is not necessarily uniformly distributed on the carrier. Furthermore, during use of the adsorbent, there is a risk that a portion of the ligand may be detached and mixed into the patient's body fluid, which can cause a serious situation if the ligand is a harmful substance.

For example, as a rheumatoid factor adsorbent, it is known that human immunoglobulin G (human-1 (JG)) is aggregated with heat or an organic solvent (e.g. dimethyl sulfoxide), and the 'a aggregate is fixed on a carrier. (Artificial organ λ: Volume 11, No. 1
No. 66-69 (1982)]. This adsorbent has the advantages of selectively and highly adsorbing rheumatoid factors, fast adsorption rate, high stability of adsorption activity, and ease of handling. However, on the other hand, since the above-mentioned aggregates are simply 1i of H--1gG physically aggregated by heat or organic solvent treatment, the bonding force between molecules is not as strong as that of the aggregates. There is a risk that the aggregate may peel off from the carrier and elute into the plasma, and if the aggregate elutes into the patient's plasma, it will be in an extremely dangerous situation due to its antigenicity. Therefore, it has been desired to develop an adsorbent for rheumatoid arthritis that does not cause the risk of the ligand peeling off from the 1U body.

■1 Purpose of the invention The present invention selectively and highly adsorbs rheumatoid arthritis prisoners in the plasma of rheumatoid patients, and the ligand is 11
It is an object of the present invention to provide a rheumatoid factor adsorbent that is free from the risk of increasing 52+m.

A further object of the present invention is to provide a rheumatoid factor adsorbent that does not require a step of immobilizing a ligand on a carrier.

A further object of the present invention is to provide a rheumatoid factor adsorption device using the above rheumatoid factor adsorbent.

According to the present invention, there are provided adsorbents and adsorption devices for rheumatoid factors as described in the following items.

(+> flA A rheumatoid factor adsorbent comprising a copolymer of a vinyl compound having an aqueous property, a vinyl compound having an aromatic ring, and a crosslinking agent.

(2) The vinyl compound exhibiting hydrophilicity is vinyl acetate or vinyl alcohol, the vinyl compound having an aromatic ring is styrene, vinyl carbazole, or allyl phenyl ether, and the crosslinking agent is 2. The adsorbent for rhinoceros larvae according to item 1, which is an ethylene crosslinking agent having a triazine ring.

(3) The vinyl compound having hydrophilicity is vinyl acetate, and the vinyl compound having the aromatic ring is 9-
The rheumatoid factor adsorbent according to item 2, wherein the rheumatoid factor is vinyl carbazole and the crosslinking agent is triallyl isocyanurate.
1 material.

(4) A rheumatoid factor adsorbent comprising a container having an inlet and outlet for fluid, and a copolymer of a hydrophilic vinyl compound, an aromatic ring-containing vinyl compound, and a crosslinking agent filled in the container. and a means for preventing the adsorbent from flowing out, which is provided in the container.

(5) The rheumatoid factor adsorption device according to item 4, wherein the device is filled with purified water and sterilized using O-1-crepe.

(6) The apparatus for adsorbing rhinoceros larvae prisoners according to item 4, wherein the outflow prevention means is a filter installed in the container.

■1 Detailed description of the invention In order to achieve the above object, the present invention combines a hydrophilic vinyl compound (hereinafter referred to as hydrophilic vinyl), an aromatic ring-containing vinyl compound, and a crosslinking agent. Made of rheumatoid factor adsorbent made of polymer.

Furthermore, the vinyl compound referred to herein may be any compound having 6==6 groups and causing copolymerization.

Furthermore, the present invention comprises a rheumatoid factor adsorption device in which the above-mentioned adsorbent is housed in a container having a fluid inlet/outlet.

The adsorbent of the present invention is made of a copolymer of hydrophilic vinyl, a vinyl compound having an aromatic ring, and a crosslinking agent. Examples of the hydrophilic vinyl include vinyl acetate, vinyl alcohol, etc., and vinyl compounds having an aromatic ring. Examples include styrene, vinyl carbazole, allyl phenyl ether, 1-
Vinylnaphthalene, 2-vinylnaphthalene, etc. are preferred. The crosslinking agent is preferably an ethylene crosslinking agent having a triazine ring, such as triallyl isocyanurate or triallyl cyanurate. These vinyl compounds are subjected to a polymerization reaction. For example, an organic solvent solution in which a hydrophilic vinyl, a crosslinking agent, and a vinyl compound having an aromatic ring are dissolved in an appropriate organic solution (for example, ethyl acetate) is mixed with an aqueous solution in which polyvinyl alcohol or the like is added as a dispersant. The suspension was heated at 60 to 80°C for 12 to 10 minutes.
Allow to react for 18 hours. Since the polymer thus obtained is in the form of particles, it can be used as an adsorbent as it is without further molding. In this case, for the purpose of the present invention, the diameter of the particles is preferably 50 to 3000 .mu.m, particularly 100 to 500 .mu.m. In addition, rheumatoid factor has a molecular Q of 1/150,000 (I
Since the polymer consists of 1 gH with a molecular weight of 1 million, the adsorption limit of the polymer is 1i1,150,000 to 1,000,000, especially 100,000.
10,000 to 3,000,000 is preferable.

In the copolymer of the present invention, the hydrophilic vinyl component is a carrier,
The vinyl component with an aromatic ring plays the role of a beam gunt.

Further, it is preferable that the hydrophilic vinyl component is greater than the aromatic ring-containing vinyl component.

The copolymer thus formed has hydrophilic properties and island-like hydrophobic groups, which is a favorable state for the adsorption of rheumatoid factors. The adsorbent of the present invention can be in the form of particles, fibers,
It can be used in any known shape such as a hollow system shape or a membrane shape, but
Particulate carriers are particularly preferably used from the viewpoint of permeability to blood and plasma, ease of handling during preparation of the adsorbent, and the like. Further, it is preferably particulate and porous.

A method for manufacturing a porous body is J (by mixing a pore-forming substance that will be extracted later to form a porous portion during molding of the polymer, and then washing with a good medium for the pore-forming substance, A porous body can be obtained.As the gap-forming substance, polymers such as polyvinyl acetate can be used.The pores formed have a pore size of 300 to 300 pores.
Preferably 0 through holes, 1+L. More preferably, the pore size is 400 to 1000 pores.

Next, the apparatus of the present invention will be explained with reference to the accompanying drawings.

FIG. 1 is a sectional view showing an example of the device of the present invention.

This device consists of a container 1 having an inlet 4 and an outlet 5 at both ends, an adsorbent 2 housed inside the container, and filters 3 and 3' installed at the inlet 4 and outlet 5 to prevent the adsorbent 2 from flowing out. It is being The filter 3.3' not only prevents the adsorbent from flowing out, but also prevents its fragments from entering the body fluid and flowing into the body. The body fluid is introduced through the body fluid inlet 4J: and the adsorbent 2r:! l! After being X-treated, the body fluid is extracted from the body fluid extraction mortar 5. The adsorbent is retained in the container by a filter 3.3'.

For convenience of use, the adsorption device of the present invention is preferably filled with purified water such as distilled water or physiological saline and sterilized using A-tocrepe to produce a product.

FIG. 2 is a schematic diagram 71'l showing an example of blood purification treatment using the adsorption device of the present invention. Blood is introduced through the blood inlet 61 and passes through the pump 7 to form a plasma fraction 11iI.
1 device 8, where it is separated into blood cells and plasma. The separated plasma is supplied to the adsorption volume 2S1 through the pump 7', and after being adsorbed, it is mixed with blood cells in a plasma/blood cell mixing device and is discharged from the blood outlet 10.

When the device of the present invention is used for extracorporeal circulation, there are two methods as follows: One method is to separate blood taken from the body into plasma components and blood cell components using a centrifugal W separator or a membrane or hollow fiber plasma separator, and then pass the plasma components through the device. One method is to return the blood to the body together with blood cell components after purification, and the other method is to directly pass the blood taken out from the body through a similar device and purify it.

The method for passing body fluids may be continuous or intermittent depending on clinical needs or the installation status of the equipment.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 6.4 g of triallylisocyanurate purified by distillation, 10 g of vinyl acetate and 1.6 g of 9-vinylcarbazole
was dissolved in 40 tJ of ethyl acetate, and to this was added 0.75 g of polyvinyl acetate and 0.0 g of α,α'-azobisbuguronitrile.
．． 36 tJ and a polyvinyl alcohol saponification degree of 88% and a polymerization degree of 1700)
Suspension polymerization was carried out using 4° of an aqueous phase consisting of 0.4 g dissolved therein. The decoupling reaction was carried out by reacting at 65°C for 12 hours, then raising the system internal temperature to 75°C, and continuing the reaction for an additional 2 hours.

After the reaction was completed, we checked the remaining amount of the added raw material by TLC and U■ specific absorption, but no raw material was detected, and only a small amount of raw material was detected.
It was assumed that 100% reaction had progressed.

The generated gel was thoroughly washed with water J3 and aretone, and the above polyvinyl acetate was extracted to obtain a porous gel. The carbazole group introduced into the gel is :)00μrQoM/
g resin.

The average particle size of the produced polymer was 150 μm.

The thus obtained polymer was examined for rheumatoid factor adsorption ability, albumin and γ-globulin adsorption ability.

Rheumatoid factor adsorption capacity was determined by adding rheumatoid patient plasma salting-out reusable solution 3i to Polymer Gel 300 and incubating it with shaking at 37°C for 2 hours. It was determined by measuring according to the method (method). 'Albumin and T-globulin adsorption ability was determined by adding 3 d of 10 TrLM phosphate buffer (11117,3) containing 11 Fl/rd each of human albumin and γ-globulin to Gel 3001 Fl, and incubating with shaking at 37°C for 2 hours. After that, the decrease in albumin and γ-globulin peaks was examined by high performance liquid chromatography, and the adsorption rate was calculated. The results are shown in Table 1.

Example 2 Triallyl isocyanurate purified by distillation 7.22 (
j, vinyl acetate 10, allyl phenyl ether 1.3
0! ? , α, α'-Azobisisobutyronitrile 0.
38g, polyvinyl acetate 0.75g and ethyl acetate 20g
, dissolved in 15 g of heptane. Water 35rd containing 1W% of polyvinyl alcohol in this organic phase.

was added, and suspension polymerization was carried out at 70°C for 20 hours. At this point, the reaction solution was subjected to gastomatography, but no residual monomer was observed. Note that the average particle size of the gel produced was 80 μIn. The generated gel was thoroughly washed with water and aretone to obtain a porous gel. Rheumatoid factor adsorption capacity, albumin, γ of the obtained polymer
- Globulin adsorption capacity was measured using the same method as in Example 1. The results are shown in Table 1.

Table 1 Latex aggregation Albumin T-globulin negative dilution rate Adsorption rate (%) Adsorption rate (%) Example 1
320. 20 Example 2 320 Q
Q blank 640 -
- From Table 1, it is clear that the adsorbent of the present invention contains albumin and γ.
- It is clear that it absorbs almost no globulin and specifically adsorbs rheumatoid factor.

■1 Effect of the invention The rheumatoid factor adsorbent of the present invention is a copolymer of a vinyl compound that determines hydrophilicity, a vinyl compound having an aromatic ring, and a crosslinking agent. Contains a vinyl compound having an aromatic ring as a component of the hand bond. Therefore, in the above copolymer, the carrier and the ligand are integrated, and unlike conventional adsorbents, there is no need for a step of fixing the ligand to the carrier. Furthermore, since the ligand of the present invention is a constituent component of a polymer, there is no risk of it peeling off during use.

Furthermore, since the adsorbent of the present invention selectively adsorbs rheumatoid factors, it can be safely used in the treatment of rheumatism.

Furthermore, according to the device of the present invention, rheumatoid factors can be easily removed.

[Brief explanation of drawings]

FIG. 1 is a sectional view of an example of the adsorption device of the present invention. FIG. 2 is a schematic diagram showing an example of blood purification treatment using the adsorption device of the present invention. 1... Container 2... Adsorbent 3.3'
... Filter 4 ... Inlet 5 ... Outlet 6 ... Blood introduction lower, 7' ... Pump 8 ... Plasma separation device 9 ... Blood cell mixing device 10 ... Blood introduction Exit patent applicant Teru Shichi Co., Ltd. Figure 1 Figure 2

Claims (6)

[Claims] (1) A rheumatoid factor adsorbent comprising a copolymer of a hydrophilic vinyl compound, an aromatic ring-containing vinyl compound, and a crosslinking agent. (2) The hydrophilic vinyl compound is vinyl acetate or vinyl alcohol, the aromatic ring-containing vinyl compound is styrene, vinyl carbazole, or allyl phenyl ether, and the crosslinking agent is ethylene having a triazine ring. The rheumatoid factor adsorbent according to claim 1, which is a crosslinking agent. (3) Claim 2, wherein the hydrophilic vinyl compound is vinyl acetate, the aromatic ring-containing vinyl compound is 9-vinylcarbazole, and the crosslinking agent is triallylisocyanurate. rheumatoid factor adsorbent. (4) a container having a fluid inlet/outlet, and a rheumatoid factor adsorbent filled in the container and made of a copolymer of a vinyl compound having hydrophilic properties, a vinyl compound having an aromatic ring, and a crosslinking agent; A rheumatoid factor adsorption device comprising: means for preventing outflow of the adsorbent provided in the container. (5) The rheumatoid factor adsorption device according to claim 4, wherein the device is filled with purified water and sterilized in an autoclave. (6) The rheumatoid factor adsorption device according to claim 1, wherein the outflow prevention means is a filter provided in the container.