JPH025097B2 - - Google Patents

Description

BACKGROUND OF THE INVENTION [Technical Field] The present invention relates to a novel adsorbent for rheumatoid factors and a method for producing the adsorbent. Plasma exchange is known to be effective in treating rheumatic diseases, but it is difficult to obtain a large amount of fresh frozen plasma necessary for plasma exchange, and there is also a risk of hepatitis infection. Therefore, treatment methods are being developed that selectively remove rheumatoid factors from autologous plasma and reuse the purified autologous plasma. The rheumatoid factor adsorbent of the present invention can be effectively used in such treatment methods. [Prior Art and Problems] Rheumatoid factor adsorbents in which a ligand is immobilized by a conventional method on a water-insoluble carrier made of a hydrophilic cross-linked polymer are already known, but the ligand in the conventional adsorbent has an amino group. It is a chemical compound, and its ability to adsorb rheumatoid factor was not necessarily sufficient. Therefore, the present inventors conducted extensive research to develop an adsorbent with excellent adsorption properties for rheumatoid factors.
The present invention was completed after discovering that an adsorbent formed by immobilizing an aromatic compound having at least one hydroxyl group on a carrier has selective and excellent rheumatoid factor adsorption ability. OBJECTS OF THE INVENTION An object of the present invention is to provide a rheumatoid factor adsorbent that can selectively and highly adsorb rheumatoid factor in plasma of rheumatoid patients. A further object of the present invention is to provide a method for producing the above-mentioned adsorbent. DETAILED DESCRIPTION OF THE INVENTION In order to achieve the above object, the present invention provides rheumatoid factor adsorption by immobilizing an aromatic compound having at least hydroxyl groups as a ligand on a water-insoluble carrier made of a hydrophilic cross-linked polymer by a conventional method. Made of wood. Furthermore, the present invention comprises a method for producing a rheumatoid factor adsorbent, which comprises binding the above-mentioned ligand to the above-mentioned carrier under acidic conditions. Examples of the hydrophilic crosslinked polymer in the present invention include crosslinked agarose, polyvinyl alcohol,
Examples include polyvinyl acetate. These polymers can be obtained by a method known per se, for example, by polymerizing monomers in the presence of a crosslinking agent such as triallylisocyanuric acid. The carrier made of the above polymer is preferably a porous body with a large surface area in order to adsorb and remove pathogenic substances with high efficiency. molecular weight 1 million) or immune complex (molecular weight
600,000 or more), the average pore size is 50~
It is 3000 μm, more preferably in the range of 100 to 500 μm. If the average pore diameter is too small, the amount of the pathogenic substance adsorbed will be small, and if it is too large, the porous material will have lower strength and surface area, which is not practical. The average pore diameter was measured using a mercury intrusion porosimeter. In this method, mercury is injected into a porous body, and the pore volume is determined from the amount of mercury that has entered, and the pore diameter is determined from the pressure required for the intrusion. The average particle size of the particulate carrier is preferably in the range of 0.05 mm to 5 mm from the viewpoint of the flow rate and circulation pressure of body fluids. After classifying the average particle size using a sieve specified in JIS-Z-8801, the intermediate value between the upper limit particle size and the lower limit particle size of each grade is taken as the particle size of each grade, and the average particle size is determined as the weight average. calculate. The ligand used in the present invention is an aromatic compound having at least one hydroxyl group. The hydroxyl group may be bonded directly to the aromatic ring or may be bonded via an alkylene group. A benzene ring is particularly preferred as the aromatic ring. Preferred examples of such compounds include phenol and β-phenethyl alcohol. These ligands are immobilized on the carrier by a method commonly used in the production of adsorbents for Affinitei chromatographs, except that the reaction is carried out under dispensing conditions, that is, at pH 3.0 to 6.5, preferably 4.0 to 5.0. For example, epichlorohydrin is used to bond via an epoxy group. The rheumatoid factor adsorbent of the present invention is used for plasma purification of rheumatoid patients by a method known per se. For example, rheumatoid factors in plasma can be adsorbed and removed by manufacturing an adsorption device by accommodating the adsorbent of the present invention in a container having a fluid outlet and supplying plasma to the adsorption device. Next, the present invention will be explained in more detail with reference to Examples and Comparative Examples. Example 1 A crosslinked polymer resin of vinyl acetate and triallylisocyanuric acid is produced by suspension polymerization, and transesterification is performed using sodium hydroxide to obtain a crosslinked polymer resin of polyvinyl alcohol-triallylisocyanuric acid. This crosslinked polymer resin is reacted with epichlorohydrin in dimethyl sulfoxide under alkaline conditions to obtain an activated resin. This activated resin is reacted with phenol under acidic conditions (PH4.4 0.5M acetic acid/sodium acetate bath) to introduce a benzene ring into the carrier via an ether bond. Excess active groups are capped with trishydroxymethylaminomethane. To the obtained adsorption resin 1, rheumatoid patient plasma salting-out precipitate reusable solution 2 was added and incubated with shaking to examine the reduction in rheumatoid factors. Latex agglutination method was used to measure rheumatoid factor.

[Table] Example 2 The epichlorohydrin activated resin obtained in Example 1 was reacted with β-phenethyl alcohol under acidic conditions (PH4.4 0.5M acetic acid/sodium acetate) to form an ether bond. A benzene ring is introduced into the carrier. Excess active groups are capped with trishydroxymethylaminomethane. To the obtained adsorption resin 1, rheumatoid patient plasma salting-out precipitation reusable solution 2 was added and incubated with shaking to examine the reduction in rheumatoid factors. Latex agglutination method was used to measure rheumatoid factor.

[Table] Comparative Example 1 A carrier made of acrylonitrile/trimellitic acid copolymer was used instead of the carrier in Example 1, and phenol was reacted with it under acidic conditions (PH4.4 0.5M acetic acid/sodium acetate bath). and combined them. To the obtained adsorbent 1, rheumatoid patient plasma salting-out precipitation reusable solution 2 was added and incubated with shaking to examine the reduction in rheumatoid factors. Latex agglutination negative dilution rate Blank 640 Comparative Example 1 640 Comparative Example 2 The epichlorohydrin activated resin obtained in Example 1 was reacted with glycine under alkaline conditions, and the excess active groups were bonded to the carrier via -NH ₂ groups. , capped with trishydroxymethylaminomethane. Reusable rheumatoid patient plasma salting-out precipitation solution 2 was added to the obtained adsorption resin 1, and the mixture was incubated with shaking to examine the reduction in rheumatoid factors. Latex agglutination method was used to measure rheumatoid factor. Latex aggregation negative dilution rate Blank 640 Comparative Example 2 640 From the above example, the adsorbent of the present invention is an adsorbent using a non-hydrophilic polymer as a carrier (Comparative Example 1)
It is clear that the rheumatoid factor adsorption ability is superior to that of the adsorbent using a compound having an amino group as a ligand (Comparative Example 2). Effects of the Invention The rheumatoid factor adsorbent of the present invention is applied to a water-insoluble carrier made of a hydrophilic crosslinked polymer by a conventional method.
It is made by immobilizing an aromatic compound having 2 hydroxyl groups as a ligand, and can selectively and highly adsorb rheumatoid factors in the plasma of rheumatoid patients. Furthermore, the method for producing the rheumatoid factor adsorbent of the present invention comprises immobilizing the above-mentioned ligand on the above-mentioned carrier under acidic conditions, and the rheumatoid factor adsorbent can be easily produced.

Claims (1)

[Claims] 1. A water-insoluble carrier made of a hydrophilic crosslinked polymer,
A rheumatoid factor adsorbent obtained by immobilizing an aromatic compound having at least one hydroxyl group as a ligand by a conventional method. 2. The rheumatoid factor adsorbent according to claim 1, wherein the hydrophilic crosslinked polymer is crosslinked agarose or polyvinyl alcohol. 3. The rheumatoid factor adsorbent according to claim 1 or 2, wherein the ligand is a compound in which at least one hydroxyl group is bonded to an aromatic ring directly or via an alkylene group. 4. The rheumatoid factor adsorbent according to claim 3, wherein the aromatic ring is a benzene ring. 5. The rheumatoid factor adsorbent according to claim 4, wherein the ligand is phenol or phenethyl alcohol. 6 A water-insoluble carrier made of a hydrophilic crosslinked polymer,
1. A method for producing a rheumatoid factor adsorbent, which comprises bonding an aromatic compound having at least one hydroxyl group as a ligand under acidic conditions by a conventional method. 7. The method for producing a rheumatoid factor adsorbent according to claim 6, wherein the acidic condition is PH3.0 to 6.5.