JPH0611334B2 - Extracorporeal circulation therapy β-lower 2 ▼ -Microglobulin adsorbent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention is an extracorporeal circulation treatment for removing β ₂ -microglobulin, which is considered to be a causative agent of the carpal tunnel syndrome in long-term dialysis patients. use beta ₂ - about microglobulin adsorbent.

[Problems to be Solved by Conventional Techniques and Inventions] In recent years, patients called carpal tunnels frequently have a disease that has undergone artificial dialysis for a long period of time. The carpal tunnel group is a disease in which the median nerve is compressed at the carpal tunnel and presents with paralysis of the median nerve. A β-fibrillar protein called an amyloid substance is deposited on the affected area of such a patient, and a precursor protein corresponding to the amyloid substance is present in the blood of the patient, which is a low molecular weight protein consisting of amino acids β
It has been shown to be ₂ -microglobulin.

So to date according to the beta ₂ - microglobulin, although attempts to isolate have been made by using a film to some extent selectively separated according to components of the blood or plasma to its size, beta ₂ - and microglobulin At the same time, since other useful proteins are removed and the amount of β ₂ -microglobulin removed is small, a method capable of removing β ₂ -microglobulin more selectively and efficiently in large amounts is desired. .

Other methods for removing β ₂ -microglobulin have not been attempted so far, but for example, an immunoadsorbent having an anti β ₂ -microglobulin antibody immobilized on a carrier or an affinity for β ₂ -microglobulin is used. A method of adsorbing and removing β ₂ -microglobulin using an adsorbent having Concanavalin A immobilized on a carrier as a compound (hereinafter, referred to as a ligand) is shown. These adsorbents beta ₂ - show high selectivity for microglobulin, anti beta ₂ - microglobulin antibody and concanavalin A
Such ligands are expensive and have drawbacks such as poor storage stability of the adsorbent and difficulty in sterilization, and are not practical as therapeutic adsorbents.

Therefore, the present inventors have solved the above-mentioned drawbacks, adsorbed and removed a large amount of β ₂ -microglobulin, had a large adsorption rate and adsorption amount of β ₂ -microglobulin, and had excellent adsorption selectivity. As a result of earnest studies, the adsorption rate and amount of β ₂ -microglobulin were significantly improved and the adsorption selectivity was also excellent when an adsorbent having a specific partition coefficient was used. It was found that the present invention has been completed.

[Means for Solving the Problems] That is, the present invention is an adsorbent obtained by immobilizing a ligand having an alkyl group having 4 or more carbon atoms on a porous water-insoluble carrier, which has a distribution coefficient for a compound having an average molecular weight of 10,000.
Β ₂ for extracorporeal circulation treatment, which has a partition coefficient of 0.05 or less for a compound of 0.3 or more and an average molecular weight of 100,000
-With regard to microglobulin adsorbents.

Example The β ₂ -microglobulin adsorbent for extracorporeal circulation treatment of the present invention is one in which a ligand having an alkyl group having 4 or more carbon atoms is immobilized on a porous water-insoluble carrier.

Examples of the porous water-insoluble carrier used in the present invention include glass beads, inorganic carriers such as silica gel, crosslinked polyvinyl alcohol, crosslinked polyacrylate, crosslinked polyacrylamide, synthetic polymer compounds such as crosslinked polystyrene, crystalline cellulose, and crosslinked cellulose. , A cross-linked agarose, an organic carrier composed of a polysaccharide such as cross-linked dextrin, further organic-organic obtained by a combination thereof, a composite carrier such as organic-inorganic, and the like as a representative example, among which a hydrophilic carrier is not It is preferable because the specific adsorption is relatively small and the adsorption selectivity of β ₂ -microglobulin is good. Here, the hydrophilic carrier refers to a carrier having a contact angle with water of 60 degrees or less when a compound constituting the carrier is formed into a flat plate. Examples of such carriers include cellulose, cellulose derivatives, polyvinyl alcohol,
Typical examples are carriers made of saponified ethylene-vinyl acetate copolymer, polyacrylamide, polyacrylic acid, polymethacrylic acid, polymethylmethacrylate, polyacrylic acid-grafted polyethylene, polyacrylamide-grafted polyethylene and glass. However, since cellulose and cellulose derivatives have relatively large mechanical strength and are strong, they are less likely to be broken or produce fine powder by an operation such as stirring, and when packed in a column, the body fluid will flow at a high flow rate. Even if it flows, it will become consolidated,
Since it does not clog, it can be flowed at a high flow rate, and its pore structure is not easily changed by high-pressure steam sterilization, etc. It is hydrophilic, and there are many hydroxyl groups that can be used for ligand binding, making it non-specific. It has excellent features such as low adsorption, high strength even if the pore volume is increased, and an adsorption capacity comparable to that of soft gel, and high blood compatibility compared with synthetic polymer compounds. And is one of the most suitable carriers for use in the present invention.

The cellulose is a so-called natural cellulose, for example, defatted cotton fiber, hemp fiber,
Typical examples thereof include pulp obtained by removing lignin and hemicellulose from wood, and purified cellulose obtained by further refining the pulp, but are not limited thereto.

Further, the cellulose derivative, for example, those in which some or all of the hydroxyl groups of cellulose have been esterified or etherified, those in which some of the hydroxyl groups of cellulose have been esterified, and some of which have been etherified, such as from cellulose It is something that has been induced.

Specific examples of those in which a part or all of the hydroxyl groups of the cellulose are esterified include, for example, cellulose acetate, cellulose propionate, cellulose butyrate, nitrocellulose, cellulose sulfate, cellulose phosphate, cellulose acetate butyrate, cellulose nitrate, and cellulose. Examples thereof include dithiocarboxylic acid ester (viscose rayon), but are not limited thereto.

Specific examples of the cellulose in which a part or all of the hydroxyl groups of the cellulose are etherified include, for example, methyl cellulose, ethyl cellulose, benzyl cellulose, triethyl cellulose, cyanethyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, aminoethyl cellulose, oxyethyl cellulose and the like. However, the present invention is not limited to these.

Further, the regenerated cellulose is cellulose obtained by molding cellulose into a cellulose derivative that is easily molded integrally and then regenerating the cellulose by hydrolysis or the like.

Among the cellulosic materials constituting the cellulosic particles, purified cellulose has few impurities, and is preferable from the viewpoint that there are few undissolved substances when dissolved, cellulose acetate, cellulose ester such as cellulose propionate, and the like. Since it dissolves in a solvent, the selection range of various manufacturing conditions at the time of particle production becomes wider, and it becomes easy to adjust the distribution coefficient of particles, the thickness of the skin layer, the size of pores in the internal network structure, etc. It is more preferable from the standpoint that the cellulosic particles can be produced, and can be easily hydrolyzed to form regenerated cellulose particles.

The cellulosic particles are prepared by dissolving a polymer solution in which cellulose, a cellulose derivative or the like is dissolved in, for example, JP-A-62
It can be manufactured by applying the apparatus and method (method combining vibration method and dry-wet coagulation method) described in JP-A-101033.

As the solvent used when preparing the polymer solution,
A solvent for cellulose, for example, copper ammonia solution,
It serves as a solvent for a mixed solution of dimethyl sulfoxide and formamide, an aqueous solution of calcium thiocyanate, and cellulose acetate which is a typical cellulose derivative. Examples thereof include dimethyl sulfoxide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone and acetone.

These solvents include methanol, ethanol, ethylene glycol, propylene glycol, in order to adjust the distribution coefficient and the like by adjusting the thickness of the skin layer of the obtained cellulosic particles and the size of the pores of the internal network structure. Glycerin, water, inorganic salts, polyethylene glycol, polyvinylpyrrolidone, etc. may be added.

The polymer solution thus prepared is jetted into the gas phase as uniform droplets by using a device as described in, for example, JP-A-62-191033, and the flight distance becomes almost spherical or more. After being made to fly, it is made to contact with a coagulant. The cellulosic particles produced in this manner are substantially spherical particles.

The coagulant is composed of a non-solvent for the polymer, but it is preferable that the coagulant has a surface tension such that the coagulant dissolves in the solvent forming the droplet and the droplet naturally wets. Specific examples of such a coagulant include water, a mixed solution of water and the good solvent or non-solvent, and a mixed solution of water and a surfactant.

Generally, when the concentration of the polymer in the polymer solution is high, the proportion of the non-solvent is low, and a coagulating liquid having a strong coagulation force such as water is used, the pores of the skin layer, that is, the distribution coefficient becomes small.

It should be noted that it is convenient that the surface of the adsorbent has a functional group that can be used for the immobilization reaction of the ligand. Representative examples of these functional groups include hydroxyl group, amino group, aldehyde group, carboxyl group, thiol group, silanol group, amide group, epoxy group, halogen group, succinylimide group,
Examples thereof include acid anhydride groups.

By the way, the porous water-insoluble carrier used in the present invention may be either a hard carrier or a soft carrier, but it is sufficient to prevent clogging during filling of the column and passage of the liquid. A hard carrier is more preferable because it requires high mechanical strength. In the case of granular gel, for example, in the case of granular gel, the gel is packed uniformly in a cylindrical column, and the relationship between the pressure loss ΔP and the flow rate when an aqueous fluid is flowed is a linear relationship up to 0.3 kg / cm ^2. Say something.

By the way, the porous water-insoluble carrier used in the present invention has a partition coefficient of 0.3 for the compound having an average molecular weight of 10,000.
Above, the partition coefficient for compounds with an average molecular weight of 100,000
Those of 0.05 or less are used. The average molecular weight 1
Dextran or pullulan is used as the compound having an average molecular weight of 100,000 and the compound having an average molecular weight of 100,000. When the partition coefficient for the compound having an average molecular weight of 10,000 is less than 0.3 or the partition coefficient for the compound having an average molecular weight of 100,000 is more than 0.05, the selectivity of β ₂ -microglobulin decreases, and other factors such as blood Albumin, which is a major protein in the product, is easily adsorbed, which causes a drawback that the adsorbed amount of β ₂ -microglobulin is also reduced.

Further, the porous water-insoluble carrier used in the present invention is a sphere (a concept including not only a substantially spherical sphere, but also an oval-shaped rotator having a minor axis / major axis up to about 0.8).
And has a number average particle size (in the case of an elliptical rotating body, a volume average particle size, that is, it is obtained as the cube root of the value obtained by multiplying the square of the long diameter by the short diameter) in the range of 300 to 600 μm. , 95
% Or more of the particles are preferably within ± 10% of the number average particle diameter. Among the porous water-insoluble carriers satisfying such conditions, cellulose particles having a network structure having a skin layer having a thickness of usually 10 μm or less on the surface and having pores of 0.1 to 10 μm inside are preferable. The porosity of the porous water-insoluble carrier is preferably about 50 to 95%.

Such particles can be applied to both the so-called plasma perfusion method in which only plasma separated by a plasma separation membrane / centrifugal plasma separator is brought into contact with adsorbed particles, and the direct blood perfusion method in which blood is brought into contact with adsorbed particles. Excellent performance even when used. Especially when it is used for the direct blood perfusion method, the number average particle size is
If it is less than 300 μm, pressure loss becomes large when β ₂ -microglobulin is selectively removed from blood, and problems such as hemolysis tend to occur easily. Further, when it exceeds 600 μm, the specific surface area becomes small and the adsorption rate becomes small. Therefore, the amount of β ₂ -microglobulin adsorbed and removed becomes small relative to the circulating amount of blood.

Further, when the proportion of particles within ± 10% of the number average particle diameter is less than 95%, pressure loss becomes large and hemolysis is likely to occur.

If the size of the network of the network inside the porous water-insoluble carrier is less than 0.1 μm, not only the adsorption rate of β ₂ -microglobulin in blood decreases but also the adsorption removal tends to be insufficient. There is. Also, if it exceeds 10 μm, the mechanical strength of the particles becomes insufficient, and the particles are easily deformed or crushed during packing into the column or during transportation, and when such deformation occurs, the pressure is The loss tends to increase, and minute debris tends to be mixed in the blood.

The porous water-insoluble carrier used in the present invention has 4 carbon atoms.
A ligand having more than one alkyl group is immobilized,
Various well-known methods can be used for the immobilization without any special limitation. However, since the adsorbent of the present invention is used for extracorporeal circulation treatment, it is important for safety to suppress the detachment and elution of ligand during sterilization or treatment, and for that purpose, it is immobilized by a covalent bond method. Is most preferred.

The reason why the ligand having an alkyl group having 4 or more carbon atoms is used in the present invention is that the adsorption ability for β ₂ -microglobulin is significantly improved when such a ligand is used. A ligand having an alkyl group with less than 4 carbon atoms has a small hydrophobicity, and thus, a satisfactory β ₂
-The ability to adsorb microglobulin is lost.

The alkyl group may be a linear, branched or cyclic aliphatic hydrocarbon, which may be a saturated hydrocarbon or one having at least one unsaturated bond. Good.

Specific examples of the ligand having an alkyl group having 4 or more carbon atoms include unsaturated hydrocarbons having the above alkyl group, alcohols, amines, thiols, carboxylic acids and their derivatives, halides, aldehydes, hydrazides, Examples include oxirane ring-containing compounds such as assocyanates and glycidyl ethers, halogenated silanes, etc. In addition to these, alkyls bonded to hetero atoms in compounds such as monoalkyl ethers of glycols and monoalkyl ethers of dicarboxylic acids. A compound having a group can be used. It should be noted that these compounds may be used alone, or may be used by mixing arbitrary two or more kinds.

The amount of the ligand provided to the porous water-insoluble carrier is
The amount is preferably 5 to 100 μmol, and particularly 15 to 40 μmol per 1 ml of the porous water-insoluble carrier. If the dose is less than 5 μmol, the adsorbed amount of β ₂ -microglobulin becomes insufficient, and in order to improve the therapeutic effect, the column solution must be increased, and the extracorporeal circulation blood or plasma should be increased accordingly. The amount will also increase, again 100 μm
If it exceeds ol, blood compatibility tends to be poor.

There are various methods of using the adsorbent of the present invention for treatment.
The simplest method is, for example, to extract the patient's blood out of the body, store it in a blood pack, and mix it with the adsorbent of the present invention to remove β ₂ -microglobulin, and then remove the adsorbent through a filter. There are ways to return blood to the patient. This method is preferred because it does not require complicated equipment. Another method is to fill the column with an adsorbent and incorporate it in an extracorporeal circulation circuit to perform adsorption removal online. Treatment methods include a method of directly perfusing whole blood and a method of separating plasma from blood and then passing the plasma through a column. The adsorbent of the present invention can be used in either method, but as described above. Most suitable for online processing.

Next, the adsorbent of the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

Example 1 Cellulofine GC-2 which is a cellulosic porous hard gel
00m (Chisso Co., Ltd., globular protein exclusion limit molecular weight 12
(000) Add water to 170 ml to make the total volume 340 ml, then add 2M
90 ml of sodium hydroxide was added to 40 ° C. To this, 31 ml of epichlorohydrin was added and reacted at 40 ° C. for 2 hours with stirring. After completion of the reaction, it was thoroughly washed with water to obtain an epoxidized gel.

To 10 ml of this epoxidized gel, 10 mg of n-hexylamine was added as a gand, and the mixture was allowed to stand in a 50% (v / v) ethanol aqueous solution at room temperature for 4 days. After completion of the reaction, the gel was thoroughly washed with water to obtain an n-hexylamine-immobilized gel.

The number average particle size of the particles contained in the obtained n-hexylamine-immobilized gel was measured by the following method, and was 539 μm.
At m, 98% of the particles were within number average particle size ± 10%.

Next, when the amount of n-hexylamine (the amount of ligand) applied to the obtained n-hexylamine-immobilized gel was measured by the following method, the sedimentation volume was 17.7 μmol per 1 ml.

The obtained n-hexylamine-immobilized gel was filtered through a glass filter to obtain an adsorbent. When the partition coefficient of the obtained adsorbent was measured by the following method, dextran T-10 (manufactured by Pharmacia, trade name, average molecular weight: 10,0
00) with 0.35 or Dextran T-11
0 (Pharmacia, trade name, average molecular weight: 110,000)
It was 0.02 when using.

The concentration of β ₂ -microglobulin 65 μg in 0.5 ml of this adsorbent
2 ml of dialyzed patient serum of 1 ml / ml was added and incubated at 37 ° C. for 2 hours. The concentrations of β ₂ -microglobulin and albumin in the supernatant were measured, and β ₂ − per 1 ml of the adsorbent was measured.
The amounts of adsorbed microglobulin and albumin were determined to be 143 μg / ml · gel and 0.4 mg / ml · gel, respectively.

This gel was packed in a column with a diameter of 31 mm and a length of 90 mm, and extracorporeal circulation was performed for 4 hours by the direct blood perfusion method in dogs. The column pressure loss was 48 at a blood flow rate of 50 ml / min.
It was ~ 53 mmHg. (Number Average Particle Size and Particle Size Distribution) An optical microscope image of several hundred particles (about 500 to 1000 particles) is processed and obtained using an image processing device (Luzex II manufactured by Nireco Co., Ltd.).

(Rigant endowment amount) The bound amine is ion-exchanged with HCl and back-titrated with NaOH.

(Partition coefficient (Kav)) Gel chromatography was performed using aqueous solutions of dextran and pullulan of various molecular weights, and the elution curve was calculated to obtain the formula: (In the formula, Vo is the amount of eluent corresponding to the peak position of the elution curve of dextran having a molecular weight of 2,000,000, Vt is the column volume,
Ve is the amount of eluate corresponding to the peak position of the sample elution curve)
Ask from.

If dextran or pruten having the desired molecular weight cannot be obtained when the partition coefficient for the desired molecular weight is obtained, interpolation or other method is used from the partition coefficient obtained using the one having the preceding and following molecular weights. Ask.

Example 2 A cetylamine-immobilized gel was obtained in the same manner as in Example 1, except that cetylamine was used instead of n-hexylamine as the ligand.

The obtained gel was filtered in the same manner as in Example 1 to form an adsorbent (ligand endowment: 24.2 μmol / ml · gel), and the partition coefficient was measured to find that it was 0.45 for dextran T-10. , And was less than 0.05 for Dextran T-110.

Next, when the adsorption amounts of β ₂ -microglobulin and albumin were measured in the same manner as in Example 1, it was 25
8 μg / ml gel and 4 mg / ml gel.

Comparative Example 1 The same as in Example 1 except that a cellulose-based porous gel (a gel having a number average particle size of 540 μm and a ratio of particles contained within ± 10% of 70%) was used as the cellulose-based porous gel. And adsorbent (giving amount of ligand: 34.6 μmol
/ Ml · gel) was obtained.

The partition coefficient of the adsorbent obtained was measured to be 0.82 for dextran T-10 and dextran T-.
When using 110, it was 0.78.

Next, the adsorption amounts of β ₂ -microglobulin and albumin were measured in the same manner as in Example 1.
It was μg / ml · gel and 12 mg / ml · gel, and it was confirmed that a large amount of albumin was adsorbed.

Comparative Example 2 A cellulosic porous gel having an average particle diameter of 350 μm and a standard deviation of particle diameter of 100 μm was manufactured as a prototype. Using this gel, an n-hexylamine-immobilized gel (ligand endowment: 31.8 μmol / ml gel) was obtained in the same manner as in Example 1. The partition coefficient of this gel was examined in the same manner as in Example 1. As a result, when using Dextran T-10, 0.45, T-
When using 110, it was less than 0.08.

When the amounts of β ₂ -microglobulin and albumin adsorbed by the dialysis patient plasma were determined in the same manner as in Example 1, they were 112 μg / ml · gel and 30 mg / ml · gel, respectively. The adsorption amount of albumin was 6 g or more in a column of 200 ml or more, and the selectivity was remarkably poor. Using this gel, a hexylamine-immobilized gel was obtained in the same manner as in Example 1.
The same extracorporeal circulation experiment of the dog as in Example 3 was performed on this gel.

After the start of extracorporeal circulation, the pressure loss rapidly increased and hemolysis occurred, which made it impossible to continue for more than 30 minutes.

Example 3 Cellulose diacetate was added at a weight ratio of dimethyl sulfoxide / propylene glycol of 4 / so that the concentration thereof was 12.5% by weight.
It was dissolved in a mixed solution of 6.

5 cm in front of the nozzle 5 mm wide with a 2 cm gap.
A parallel plate electrode having a size of m and a length of 25 cm in the droplet advancing direction was installed, and a DC voltage of 800 V was applied between the electrode and the nozzle. From the orifice with a diameter of 250 μm provided in this nozzle, the solution held at 145 ° C. was discharged at a linear velocity of 7.8 m / sec while vibrating at 3850 Hz to form uniform droplets of the solution, and the air was blown in the air. After flying about 3m, 23
Particles of cellulose diacetate were obtained by infiltrating into 10% methanol aqueous solution at ℃ to coagulate.

The obtained cellulose diacetate particles were put into a 0.6% caustic soda aqueous solution at 50 ° C., stirred for 2 hours, collected, and then neutralized and washed with water to obtain regenerated cellulose particles.

When the number average particle size of the obtained regenerated cellulose particles was measured by the following method, it was 430 μm, and all the particles were within the average particle size ± 5%.

After replacing the liquid in the obtained regenerated cellulose particles with ethanol, the carbon dioxide gas was dried at the critical point, and gold was vapor deposited and then observed with a scanning electron microscope.
There was a skin layer of 2 μm, and the porous network structure had a pore size of about 0.2 to 2 μm.

The partition coefficients of the particles for Dextran T-10 and T-110 were measured by the following method and were 0.67 and 0, respectively.

The regenerated cellulose particles were packed in a column having an inner diameter of 14 mm and a length of 7 cm, and fresh blood of cattle to which heparin was added at 30 units / ml was kept warm at 37 ° C., and the flow rate was gradually increased to measure the pressure loss. However, the pressure loss increased almost linearly as the linear velocity increased, but it was 50 mmH even at 8 cm / min.
With g, this value did not change even after continuous operation for 1 hour, and direct blood perfusion was possible (note that pressure loss
It was judged that blood perfusion was possible for those with 100 mmHg or less).

Next, in the same manner as in Example 1, the regenerated cellulose particles were added.
The amount of β ₂ -microglobulin and albumin adsorbed was determined by immobilizing n-hexylamine.
2 μg / ml gel and 4 mg / ml gel.

When this gel was packed in a column having a diameter of 31 mm and a length of 90 mm and extracorporeal circulation was carried out for 4 hours by the direct blood perfusion method of the dog, the pressure loss was 62 mmHg at a blood flow rate of 50 ml / min.

Also, the loss of blood cell components was small, and the numbers of white blood cells, red blood cells, and platelets in the blood at the inlet and outlet of the column were compared 2.5 hours after the start of extracorporeal circulation.Each blood cell component at the outlet was 101% of the inlet and 100% at the inlet, respectively. %, 94%, and there was no adherence or loss of blood cell components.

(Selectivity) Lysozyme and albumin were dissolved in 0.025M phosphate buffer adjusted to pH 7.4 to a concentration of 3 mg / ml and 7.3 mg / ml, respectively. Then, a cellulosic particle to which a plasma protein-adsorbing ligand is immobilized is added so that the ratio becomes 1 volume, and the mixture is shaken at 37 ° C for 2 hours, and then the concentration of the supernatant is measured to determine the adsorption rate for each. Ask for.

Example 4 89% of particles having a number average particle diameter of 450 μm have a number average particle diameter of ± 10.
An n-hexylamine-immobilized gel was obtained in the same manner as in Example 1 by using commercially available regenerated cellulose particles within the range of 100% (ligand endowment: 38 μmol / ml gel). When this gel was subjected to an adsorption experiment on dialysis patient serum (β ₂ -microglobulin concentration 65 μg / ml) in the same manner as in Example 1, the adsorbent 1 was obtained.
Adsorption amount of β ₂ -microglobulin per ml is 135 μg
/ Ml gel.

However, when the extracorporeal circulation of the dog was performed in the same manner as in Example 1, the blood flow rate was 15 ml / min and the pressure loss exceeded 100 mHg, so the experiment was stopped.

Example 5 The number average particle size was 270 μm and 100% of the particles were ± 5 of the number average particle size in the same manner as in Example 1 except that the conditions for forming uniform droplets were changed.
% Regenerated cellulose particles were obtained. Using these particles, a cetylamine-immobilized gel was obtained in the same manner as in Example 2 (ligand endowment: 31 μmol / ml · gel). When this gel was subjected to an adsorption experiment with dialysis patient serum (β ₂ -microglobulin concentration of 65 μg / ml) in the same manner as in Example 1, the amount of β ₂ -microglobulin adsorbed per 1 ml of the adsorbent was 25.
It was 1 μg / ml · gel, and the adsorption capacity was comparable to that of Example 1. Using these particles, the pressure loss was examined in the extracorporeal circulation of the dog in the same manner as in Example 1. It was 100 mmHg at 35 ml / min.
Exceeded.

Comparative Example 3 n-Hexylamine was immobilized on commercially available regenerated cellulose particles having a partition coefficient of 0.3 for dextran having a molecular weight of 110,000 in the same manner as in Example 1 (the amount of ligand imparted: 1
The adsorption rate of β ₂ -microglobulin and albumin was measured to be 64% each.
And 26%, and recognized that a large amount of albumin was adsorbed.

EFFECTS OF THE INVENTION Since the adsorbent of the present invention has a specific partition coefficient, the pressure loss when adsorbing and removing β ₂ -microglobulin from blood, particularly by direct blood perfusion method, becomes small, and problems such as hemolysis occur. Is less likely to occur, and the selectivity is also improved,
This has the effect of increasing the amount of adsorption.

Claims (2)

[Claims] 1. An adsorbent comprising a porous water-insoluble carrier and a ligand having an alkyl group having 4 or more carbon atoms fixed thereon, which has a partition coefficient of 0.3 for a compound having an average molecular weight of 10,000.
The β ₂ -microglobulin adsorbent for extracorporeal circulation treatment, which has a partition coefficient of 0.05 or less for a compound having an average molecular weight of 100,000. 2. 95% or more of the particles of the porous water-insoluble carrier are within ± 10% of the number average particle diameter, and the number average particle diameter is 300 to 6
The β ₂ -microglobulin adsorbent according to claim 1, which has a diameter of 00 μm.