JP2777604B2 - Adsorbent for body fluid treatment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial application field) The present invention is intended to adsorb substances present in body fluids and interacting with anionic groups, for example, low-density lipoproteins, certain viruses and the like. Of the adsorbent.

In recent years, advances in medicine, especially internal medicine, hematology, immunology, and clinical test methods, have revealed the malignant substances in blood that are considered to be closely related to the cause or progression of disease. Among them, a causal link is known to be low-density lipoprotein in familial hypercholesterolemia.

As is well known, an increase in lipids in blood, especially low-density lipoprotein, is considered to be closely related to the cause or progression of arteriosclerosis. As arteriosclerosis progresses, the possibility of serious symptoms of the circulatory system such as myocardial infarction and cerebral infarction becomes extremely high, and mortality is also high. Thus, by selectively adsorbing and removing low-density lipoprotein from body fluid components such as blood and plasma, it was expected to prevent the progression of the disease as described above, reduce symptoms, and further accelerate healing. .

(Prior art) Conventional techniques usable for the above purpose include a method of forming an insoluble complex of heparin and low-density lipoprotein and removing the same by filtration, and separating blood into blood cells and plasma first. Thereafter, a plasma component is passed through a plasma component separation filter, a method of separating and separating low-density lipoprotein which is a high-molecular-weight protein, a method of adsorbing and removing low-density lipoprotein by an agarose gel to which an anti-low-density lipoprotein antibody is bound,
There is a method of adsorbing and removing low-density lipoprotein using an adsorbent in which a sulfated polysaccharide is bound to a water-insoluble gel.

However, in the method, the heparin adsorbent must be used to remove excess heparin added to the plasma, and the apparatus becomes large-scale and the operation becomes complicated. In the method of removing all the proteins, useful biological components are also removed.In this method, low-density lipoprotein can be specifically adsorbed. It is impossible to guarantee sterility, and the antibody is expensive.In the method, it is possible to selectively adsorb low-density lipoprotein, but since whole blood cannot be directly treated with the adsorbent, blood cells and plasma However, there is a drawback in that a device for separating is required, and the operation becomes complicated.

(Problems to be Solved by the Invention) In view of the above-mentioned problems of the prior art, there is provided a low-density lipoprotein adsorbent which can selectively adsorb low-density lipoprotein and can treat whole blood as it is, and which is easy to operate. This is the most important object of the present invention.

(Means for Solving the Problems) The present inventors have conducted intensive studies along the above-mentioned object, and
Using a hollow fiber-like totally porous body as a carrier, by introducing an anionic group derived from a low molecular compound at least in the vicinity of the surface of the structural part of the porous body, there is no coagulation of blood even when directly treating whole blood, Platelet loss was low, and it was found that low-density lipoprotein could be selectively adsorbed.
An anionic group derived from a low-molecular compound is introduced near the surface of the structural part of the hollow fiber-like totally porous body, and an anionic group derived from a chain-like high molecular compound is introduced far away from the structural part. As a result, they have found that the ability to adsorb a low-density lipoprotein can be further improved, and have led to the present invention.

That is, the present invention is a bodily fluid treatment adsorbent characterized by having an anionic group derived from a low molecular weight compound at least in the vicinity of the surface of the structural part of the hollow fiber-like totally porous body, and the present invention Having an anionic group derived from a low molecular weight compound near the surface of the structural part of the hollow fiber-like totally porous body, and having an anionic group derived from a chain high molecular compound far away from the structural part This is an adsorbent for treating body fluid.

Conventionally, when attempting to adsorb a low-density lipoprotein having a very large molecule with an adsorbent, a substance having a long-chain structure, such as heparin or dextran sulfate, is used as a ligand to interact with the low-density lipoprotein. Therefore, it is considered that adsorption is not possible unless the ligand is extended sufficiently far from the surface of the carrier.In fact, when a porous gel is used as the carrier, even if a short molecule is used as the ligand, the low-density lipoprotein can be sufficiently absorbed. It was impossible to adsorb. In contrast, the present inventors have found that, by using a hollow fiber-like totally porous material as a carrier, a sufficient amount of low-density lipoprotein can be adsorbed surprisingly even when a short molecule is used as a ligand. . It is not clear why short molecules can adsorb low-density lipoproteins efficiently, but adsorbents that bind short molecules have the advantage that the antigenicity of the molecules themselves is low and that the binding of ligands during sterilization is difficult to break. This fact is a breakthrough as an adsorbent. Furthermore, if short molecules and long molecules are combined, low specific gravity lipoproteins can be adsorbed by short molecules near the wall surface of the structure of the hollow fiber-like totally porous body and long molecules in the space of micropores. Lipoprotein can be adsorbed with very high efficiency.

In the present invention, the hollow fiber-shaped totally porous body refers to a porous structure in which the appearance is a hollow fiber shape and a fine structure of a hollow fiber structure portion (hereinafter, referred to as a membrane) communicates from the inner surface to the outer surface of the membrane. Say what you have on the whole.

The pore size of the membrane can be freely selected depending on the size and shape of the substance to be adsorbed, but it is preferable that the pore diameter is such that the substance to be adsorbed can freely pass therethrough and that the surface to which the substance to be adsorbed can come into contact is sufficient. When the average pore diameter is defined as a pore diameter indicating a pore volume of 1/2 of the total pore volume on a pore diameter-pore volume integral curve obtained by a mercury porosimeter, the hollow fiber-like total porous body used in the present invention is Average pore size from 0.005μm to 3μ
m is preferable and can be selected according to the size of the substance to be adsorbed. More preferred average pore size is from 0.01 μm to 2 μm.
μm, preferably in the range of 0.02 μm to 1 μm. When the pore surface area of the porous structure of the membrane is defined as a value obtained from the nitrogen adsorption amount using a BET type surface area measuring device, the pore surface area of the hollow fiber-like totally porous body used in the present invention is 5 m ² / g or more. It is more preferably at least 10 m ² / g, more preferably at least 15 m ² / g. The inner diameter of the hollow fiber is preferably 30 μm or more, and from 50 μm
The thickness is more preferably 5 mm, and more preferably 100 μm to 1 mm. The thickness of the hollow fiber is preferably 5 μm or more, more preferably 10 μm to 1 mm, and more preferably 20 μm to 500 μm.

As the material of the hollow fiber, any of cellulose, cellulose derivative, polyvinyl alcohol, a hydrophilic material such as ethylene-vinyl alcohol copolymer, polyethylene, polypropylene, polysulfone, and a hydrophobic material such as polytetrafluoroethylene can be used. In the case of a hydrophobic material, since filtration of an aqueous liquid is difficult, it is preferable to perform a hydrophilic treatment by a method of coating a hydrophilic material, making the surface hydrophilic by a chemical treatment, or making the surface hydrophilic by a plasma treatment. Further, in order to introduce an anionic group, for example, when fixing a ligand having an anionic group, a hydroxyl group, an amino group, a carboxyl group, which can easily fix the ligand having an anionic group on the surface of a hollow fiber-like totally porous material. It is preferable to have a functional group such as a thiol group, but even if it does not have the functional group, it may have an anionic group by a method such as plasma treatment or embedding coating of a ligand having an anionic group. The ligand can be immobilized.

The method of immobilizing a ligand having an anionic group on the surface of a hollow fiber-like totally porous material includes covalent bond, ionic bond, physical adsorption,
Any known method such as embedding and insolubilization of the precipitate on the membrane surface can be used, but immobilization and insolubilization by covalent bonds are preferred in view of the elution of the ligand having an anionic group. For example, usually, immobilized enzymes, known carrier activation methods used in affinity chromatography,
An immobilization method can be used. To illustrate the activation method,
Examples thereof include a cyanogen halide method, a periodic acid method, a crosslinking reagent method, and an epoxide method. The activation method is a nucleophilic reaction in which the surface of a hollow fiber-like totally porous material is modified into a highly reactive state, and the active hydrogen such as an amino group, a hydroxyl group, a carboxyl group, or a thiol group of a ligand having an anionic group is formed. It is only necessary to be able to perform a substitution and / or addition reaction with the group, and it is not limited to the above examples.

Further, the hollow fiber-like totally porous body itself may be made of a material having an anionic group.

In the present invention, the anionic group is a sulfonic acid group,
A functional group that exhibits a negative charge in a body fluid, such as a sulfate group, a phosphate group, and a carboxyl group.

Further, in the present invention, the term “near the surface” refers to 200 ° from the surface of the structural part (material itself) constituting the hollow fiber-shaped totally porous body.
Up to and including the surface of the structure. This distance corresponds to the diameter of the low density lipoprotein.

The method of introducing an anionic group derived from a low molecular compound in the vicinity of the surface of the structural portion of the hollow fiber-like totally porous body is a method of introducing a low molecular compound having an anionic group into the surface of the structural part of the hollow fiber-like totally porous body. And a method such as a covalent bond or an ionic bond.

Since the low-density lipoprotein has cationic amino acid residues on its surface, it forms an electrostatic interaction with an anionic group present on the surface of the structure of the hollow fiber-like fully porous material, resulting in electrostatic attraction. Is adsorbed. In addition to low-density lipoproteins, proteins, peptides, and viruses that have a cationic domain on the surface, such as activated complement components C3a and C4
a, C5a, certain retroviruses and the like are also adsorbed by the adsorbent of the present invention.

In claim 2 of the present invention, the meaning of having an anionic group far away from the structural part means that the anionic group is located at a distance of 200 ° or more from the surface of the structural part constituting the hollow fiber-shaped totally porous body. Means to have

The method of introducing an anionic group derived from a chain-like polymer compound to the far side of the structural portion of the hollow-fiber-like totally porous body is a method of introducing a chain-like polymer compound having an anionic group into a structure of the hollow-fiber-like totally porous body. And a method of extending a graft chain having an anionic group from the surface of the structure portion of the hollow fiber-like totally porous body.

Chain of the polymer compound having an anionic group molecular weight (hereinafter, referred to as a polyanion) 10 ⁷ preferably from 600, 10
00 to 5 × 10 ⁶ is more preferable, and 2000 to 10 ⁶ is more preferable.

Examples of the polyanion include polyacrylic acid, polymethacrylic acid, polyvinylsulfonic acid, polyvinylsulfuric acid, polymaleic acid, polyfumaric acid and derivatives thereof as vinyl-based synthetic polyanions, and polystyrenesulfonic acid, polystyrene phosphorus as styrene-based synthetic polyanions. Acids and the like, polyglutamic acid and polyaspartic acid as the peptide-based polyanion, poly-U, poly-A and the like as the nucleic acid-based polyanion, polyphosphate anion as a synthetic polyanion, poly-α-methylstyrenesulfonic acid, Styrene-methacrylic acid copolymer and the like, and polysaccharide-based polyanions include heparin, dextran sulfate, chondroitin sulfate, alginic acid, pectin, hyaluronic acid, and derivatives thereof and the like. It is. The polyanion referred to in the present invention is not limited to the above examples.

By having anionic groups both near and far from the surface of the hollow fiber-like fully porous structure, low density lipoprotein can be adsorbed to both the surface of the hollow fiber-like fully porous structure and the space of the micropores. As a result, the adsorbed amount of the low-density lipoprotein per unit volume is drastically increased, and the low-density lipoprotein can be adsorbed with high efficiency.

Performing a treatment for suppressing platelet adhesion and blood coagulation on the inner surface of the adsorbent for treating body fluid of the present invention gives more preferable results.

The body fluid treatment adsorbent described above is bundled in a large number, and both ends thereof are bonded and fixed, and the end is filled in a container, and the body fluid treatment adsorbent has a structure in which the outside of the container communicates with the body fluid treatment adsorbent inner surface. Used as an adsorber. That is, the body fluid of the patient is introduced into the inner surface of the adsorbent for body fluid treatment of the adsorber for body fluid treatment, and the substance to be adsorbed that has moved from the inner surface of the adsorbent for body fluid treatment to the membrane (hollow structure) is converted into an anion fixed to the membrane. The bodily fluid component that has interacted with the active group and that has been adsorbed and not adsorbed is also used as an adsorber suitable for use in which it is discharged outside the container. In addition, in order to facilitate the movement of the substance to be adsorbed to the membrane, a structure is provided in which the outside of the container communicates with the outer surface of the adsorbent for bodily fluid treatment so that the bodily fluid can be easily moved from the inner surface of the hollow fiber to the outer surface. Structure.

 Hereinafter, the present invention will be described with reference to the drawings.

FIG. 1 is a schematic diagram showing an example of an adsorption device using the adsorbent for treating body fluid of the present invention, and FIG. 2 is a schematic diagram showing another example. FIG. 3 is a schematic diagram showing the state of the presence of an anionic group in the micropores of the adsorbent for treating body fluid of the present invention.

In FIG. 1, a bodily fluid is introduced from a bodily fluid inlet 1,
The body fluid is transferred to the body fluid treatment adsorber 3 by the body fluid transporting means 2.
In the bodily fluid treatment adsorber 3, the bodily fluid is sent to the inner surface of the bodily fluid treatment adsorbent 4, and the liquid component permeates from the inner surface into the inside of the membrane (porous structure). It moves to the outer surface of the adsorbent 4, and again the adsorbent 4 for body fluid treatment.
Returns to the inner surface and joins the body fluid. In this process, the substance to be adsorbed (such as low-density lipoprotein) is adsorbed to the anionic group fixed to the membrane of the adsorbent for treating body fluid, and the body fluid having the substance to be adsorbed is led out from the body fluid outlet 5. You.

FIG. 3 schematically shows the presence of anionic groups in the micropores of the body fluid treatment adsorbent. FIG. 3A shows the vicinity of the surface 7 of the structural portion 6 of the hollow fiber-like fully porous body. 3 has an anionic group 8 derived from a low molecular compound in the vicinity of the surface 7 and has a chain-like structure at a distant position 9 of the structural portion 6. Having an anionic group 8 derived from the high molecular compound described above. The substance to be adsorbed (such as a low-density lipoprotein) interacts with the anionic group in the micropore when passing through the micropore, and is adsorbed.

FIG. 2 is a schematic cross-sectional view showing another example of an adsorption device using the adsorbent for treating a body fluid of the present invention, wherein a bodily fluid is introduced from a body fluid introduction port 1 and is adsorbed by the body fluid transport means 2. Sent to 3. In the body fluid treatment adsorber 3, the body fluid is sent to the inner surface of the body fluid treatment adsorbent 4, and the liquid component is sent from the inner surface to the outer surface of the body fluid treatment adsorbent 4 through the membrane. In this process, the substance to be adsorbed (such as a low-density lipoprotein) interacts with the anionic group in the membrane and is adsorbed. The liquid component from which the substance to be adsorbed has been adsorbed and removed is sent by the liquid component transport means 10 in the direction of the bodily fluid outlet 5, merges with the bodily fluid, and is then led out of the bodily fluid outlet 5.

The body fluid treatment adsorbent of the present invention has been described above. Hereinafter, the present invention will be described more specifically by way of examples.

(Example) Example 1 Poly-2-hydroxyethyl methacrylate (poly-HEMA) was used as a hollow fiber-shaped totally porous body in a polyethylene hollow fiber.
And thermally crosslinked. The polyethylene hollow fiber having an inner diameter of 340 μm, an outer diameter of 440 μm, a film thickness of 50 μm, an average pore diameter of 0.3 μm, and a surface area of 21 m ² / g was used. Poly HEMA is 2-hydroxyethyl methacrylate 100 g ethanol 64
After adding 0 g and adding 0.4 g of azobisisobutyronitrile, the mixture was polymerized with stirring at 57 ° C. for 7.5 hours, precipitated in water, and purified. Polyethylene hollow fibers are coated with poly-HEMA by dipping polyethylene hollow fibers in a 2% by weight ethanol solution of poly-HEMA,
After leaving for a minute, it was taken out and dried at 50 ° C. for 1 hour. The obtained hollow fibers are bundled, and both ends are fixed with a silicone adhesive,
The bundle was made into a bundle of 50 hollow fibers having an effective length of 15 cm, and both ends were thermally crosslinked at 120 ° C. for 3 hours while the hollow fibers were fixed so as not to shrink.

Next, an epoxy group was introduced into the above-mentioned hollow fiber-shaped totally porous body. First, a mixed solution of 80 ml of dimethyl sulfoxide, 80 ml of epibromohydrin and 30 g of 40% by weight of sodium hydroxide was prepared, and 2.4 m of hollow fiber-like all-porous material was placed inside the hollow fiber.
The flow was at a flow rate of l / min. The temperature of the mixed solution was 30 ° C., and the flow rate of the filtrate coming out of the hollow fiber was not controlled. In this state, the reaction was carried out for 5 hours, and then, washed with acetone and water.

Thereafter, taurine was fixed to the hollow fiber-like totally porous body into which the epoxy group was introduced. First, 0.1 g of taurine 0.1M
After dissolving in 100 ml of a sodium carbonate buffer (pH 9.8), the solution was flowed at a flow rate of 2.4 ml / min inside the hollow fiber-like totally porous body. The temperature of the taurine solution was 50 ° C., and the flow rate of the filtrate coming out of the hollow fiber was not controlled. In this state
The mixture was reacted for 16 hours, and then washed with water to obtain an adsorbent for purifying body fluid to which taurine was fixed. According to the method for producing the adsorbent, the position where the anionic group (sulfonic acid group of taurine) exists is in the vicinity of the structural part of the hollow fiber-like fully porous body (within 200 mm from the surface of the structural part). . The fixed amount of taurine is 1 ml in the volume of the porous part of the hollow fiber-like porous body.
It was equivalent to 60 μ per unit.

After drying the bodily fluid treatment adsorbent obtained as described above, both ends are fixed with a urethane adsorbent in a tubular container, and after cutting both ends, a nozzle is formed, and a bodily fluid as shown in FIG. 4 is formed. A treatment adsorber was manufactured. The effective length of the bodily fluid treatment adsorbent was 7.5 cm, and the number was 50. In FIG. 4, 11 is a body fluid inlet side nozzle, 12 is a blood outlet side nozzle, 4 is a body fluid treatment adsorbent, and 13 is a liquid component leading nozzle.

Using the body fluid treatment adsorber shown in FIG. 4, the body fluid treatment adsorption device shown in FIG. 2 was assembled, and the following adsorption experiment was conducted.

Heparinized whole blood from a patient with familial hypercholesterolemia was introduced through the body fluid outlet 1 and sent to the body fluid treatment adsorber 3 by the pump 2 at 0.5 ml / min. Plasma, which is a liquid component, is filtered by the adsorbent 4 for body fluid treatment, and the plasma is sent to the body fluid outlet by the pump 10 to be combined with blood rich in blood cells derived from the adsorber 3 for body fluid treatment. Removed from Exit 5. Pump 10 flow rate is 1/5 of pump 2 flow rate
In this state, 6 ml of whole blood was recirculated for 30 minutes.

During the circulation, no coagulation or hemolysis was observed, and stable circulation was performed. Total cholesterol in blood (plasma) before and after treatment was measured by an enzyme method. In the blood of patients with familial hypercholesterolemia, cholesterol is mostly derived from low density lipoproteins.

As a result, the total cholesterol was 510 mg / dl before the treatment, but decreased to 190 mg / dl after the treatment.

Comparative Example 1 Taurine was immobilized using CNBr-activated Sepharose 4B (Pharmacia Japan Co., Ltd.), which is an agarose-based totally porous spherical gel, instead of using a hollow fiber-like totally porous body. The method of immobilizing taurine on CNBr-activated Cephalol 4B followed the usual method recommended by Pharmacia. The fixed amount of taurine was 50 μeq / ml (wet volume).

Comparative Example 1 Taurine-immobilized Sepharose 4B having the same porous structure partial volume as the porous structure portion of the bodily fluid treatment adsorber of Example 1 was added to 6 ml of the same blood used in Example 1. And incubated for 30 minutes with shaking. As a result, the total cholesterol was 510 mg / dl before the treatment, but was not so reduced to 450 mg / dl after the treatment.

Example 2 As the hollow fiber-like totally porous body, the same one as in Example 1 was used, and the method of introducing an epoxy group into the hollow fiber-like totally porous body was performed in the same manner as in Example 1.

In order to introduce an anionic group, dextran sulfate having a molecular weight of 50,000 and taurine were reacted with the hollow fiber-like totally porous body after the introduction of the epoxy group. First, a 0.1% by weight aqueous solution of dextranic acid adjusted to pH 13 with sodium hydroxide was prepared, brought to a temperature of 50 ° C, and flowed at a flow rate of 0.24 ml / min. It was allowed to flow inside the hollow fibers of the body and circulated for 1 hour. At this time, the flow rate of the filtrate was not adjusted. Next, the hollow fiber-like totally porous body was washed with water, and then, a solution prepared by dissolving 0.1 g of taurine in a 0.1 M sodium carbonate buffer (pH 9.8) was prepared. And circulated for 15 hours. At this time, the temperature of the taurine solution was 50 ° C., and the flow rate of the filtrate was not controlled. Thereafter, the resultant was washed with water and dried to obtain an adsorbent for treating body fluid. According to the above production method, an anionic group mainly derived from taurine is present in the vicinity of the structural part of the hollow fiber-like totally porous body, and an anionic group derived from dextran sulfate is present in a distance of the structural part. .

The adsorbent for body fluid treatment obtained by the above method was used as an adsorber in the same manner as in Example 1, and an adsorption experiment was performed in the same manner as in Example 1. As a result, the cholesterol concentration before treatment was 51
It was 0 mg / dl, but decreased to 90 mg / dl after treatment.

Example 3 A body fluid treatment adsorber was manufactured in the same manner as in Example 1.

Using an autoclave sterilizer, the body fluid treatment device was
The solution was sterilized by wet heat at 1 ° C. for 20 minutes.

An adsorption experiment was performed in the same manner as in Example 1 using the adsorber for treating body fluid after wet heat sterilization. As a result, the cholesterol concentration before the treatment was 480 mg / dl,
It had dropped to 0 mg / dl.

For comparison, the same hollow fiber-like porous body as that of Example 1 was used, and a method of introducing an epoxy group into the hollow fiber-like porous body was also performed in the same manner as in Example 1.

Heparin was fixed to a hollow fiber-like porous body into which an epoxy group had been introduced in the same manner as in Example 1 except that heparin sodium (Sigma, molecular weight: 5,000 to 20,000) was used instead of taurine. The fixed amount of heparin is
The amount was 7.2 mg per 1 ml of the volume of the porous portion of the hollow fiber-like totally porous body.

The adsorbent for body fluid treatment obtained as described above was assembled into a body fluid treatment adsorber in the same manner as in Example 1.

 The body fluid treatment device was subjected to wet heat sterilization under the same conditions as described above.

When an adsorption experiment was carried out in the same manner as in Example 1 using an adsorber for treating body fluid after wet heat sterilization, the cholesterol concentration before the treatment was 480 mg / dl, whereas after the treatment, the cholesterol concentration was 360 mg / dl.
And did not drop much. It is considered that part of the heparin was removed from the hollow fiber-like totally porous body by the wet heat sterilization treatment.

(Effects of the Invention) As described above, by using the adsorbent for treating body fluid of the present invention, when adsorbing a substance that interacts with an anionic group from a body fluid, it has low antigenicity and sterilization. A stable adsorbent was obtained. Further, as a result of the extremely high adsorption capacity as an adsorbent, the substance to be adsorbed can be adsorbed efficiently with a small priming volume.

The adsorbent for treating body fluids of the present invention is a malignant substance that is expressed in body fluids and is considered to be closely related to the cause or progression of disease, particularly, low-density lipoprotein, anaphylatoxin, retrovirus, etc. It is particularly useful for the adsorption and removal of substances that interact with anionic groups.

[Brief description of the drawings]

FIG. 1 is a schematic diagram showing an example of an adsorption device using the adsorbent for body fluid treatment of the present invention, FIG. 2 is a schematic diagram showing another example of an adsorption device using the adsorbent for body fluid treatment of the present invention, and FIG. 3 and 4 are schematic diagrams showing the presence of anionic groups in the micropores of the body fluid treating adsorbent of the present invention, and FIG. 4 shows an example of an adsorber using the body fluid treating adsorbent of the present invention. It is a schematic diagram. DESCRIPTION OF SYMBOLS 1 ... Body fluid inlet 2 ... Body fluid transport means (pump) 3 ... Body fluid treatment adsorber 4 ... Body fluid treatment adsorbent 5 ... Body fluid outlet 6 ... Structure part of hollow fiber-like totally porous body 7 ... Surface of the structure part 8 ... Anionic group 9 ... Distant of the structure part 10 ... Liquid component transport means (pump) 11 ... Body fluid inlet side nozzle 12 ... Body fluid outlet side nozzle 13 ... Nozzle for deriving liquid components

Claims (2)

(57) [Claims] 1. An adsorbent for treating body fluid, comprising an anionic group derived from a low molecular weight compound at least in the vicinity of the surface of a structural portion of a hollow fiber-like totally porous body. 2. An anionic group having an anionic group derived from a low molecular weight compound near the surface of a structural portion of a hollow fiber-like totally porous material, and an anionic group derived from a chain high molecular compound far from the structural portion. An adsorbent for treating body fluid, comprising a group.