JPH0260660A - Adsorbent for treating body fluid - Google Patents

Abstract

PURPOSE:To allow the selective adsorption of low sp. gr. lipoprotein and the treatment of the whole blood as it is by providing anionic groups near the surfaces of the structural body parts of hollow yarn-shaped fully porous bodies and providing the anionic groups to the part further from the structural body parts as well at need. CONSTITUTION:The body fluid is introduced form a body fluid introducing port 1 and is sent by a body fluid transporting means 2 to an adsorber 3 for treating the body fluid. The body fluid is sent in the adsorber 3 for treating the body fluid to the inside surface of adsorbents 4 for treating the body fluid. The liquid components penetrate gradually from the inside surfaces into the films (porous structural bodies). Part of the liquid components migrate to the outside surfaces of the adsorbents 4 and return again to the inside surfaces of the adsorbents 4 so as to join with the body fluid. The materials to be adsorbed (low sp. lipoprotein, etc.) are adsorbed by the anionic groups fixed to the films of the adsorbents in this process and the body fluid from which the materials to be adsorbed are adsorbed is led out of a body fluid leading out port 5. The anionic groups 8 are provided even to the parts near the surfaces 7 and further 9 from the structural body parts 6 as well at need.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention is used to adsorb substances that exist in body fluids and interact with anionic groups, such as low-density riboproteins and certain viruses. The invention relates to an adsorbent.

In recent years, advances in medicine, particularly in internal medicine, hematology, immunology, and clinical testing methods, have led to the discovery of malignant substances in the blood that are thought to be closely related to the cause or progression of diseases. Among these, the one with a clear causal relationship is low-density riboprotein in familial hypercholesterolemia.

As is well known, an increase in blood lipids, particularly low-density riboproteins, is thought to be closely related to the cause or progression of arteriosclerosis. Myocardial infarction occurs when arteriosclerosis progresses,
The possibility of suffering from serious circulatory system symptoms such as cerebral infarction is extremely high, and the mortality rate is also high. Therefore, it was hoped that by selectively adsorbing and removing low-density riboproteins from body fluid components such as blood and plasma, it would be possible to prevent the progression of the above-mentioned diseases, alleviate symptoms, and even speed up healing. .

(Prior Art) Conventional techniques that can be used for the above purpose include: ■ Forming an insoluble complex between heparin and low-density riboprotein and removing this by filtration; ■ A method in which blood is first separated into blood cells and plasma. After separation, the plasma components are passed through a plasma component separation filter,
A method for separating low-density riboproteins, which are high molecular weight proteins, by filtration; ■ A method for adsorbing and removing low-density riboproteins using agarose gel bound with anti-low-density riboprotein antibodies; ■ Adsorption of sulfate polysaccharide bound to a water-insoluble gel. There is a method of adsorbing and removing low-density riboprotein using the body.

However, in the method (■), a heparin adsorbent must be used to remove excess heparin added to the plasma, making the device large-scale and complicated to operate. As a result of removing all high molecular weight proteins, useful biological components are also removed.
Although method (2) can specifically adsorb low-density riboproteins, it is difficult to sterilize because it uses a protein called an antibody, and it is impossible to guarantee complete sterility.
Antibodies are expensive, and although method (2) can selectively adsorb low-density riboproteins, whole blood cannot be directly treated with an adsorbent, so a device to separate blood cells and plasma is required.
This method has drawbacks such as complicated operations.

(Problems to be Solved by the Invention) In view of the problems of the prior art described above, it is an object of the present invention to provide a low-density riboprotein adsorbent that can selectively adsorb low-density riboproteins, can process whole blood as it is, and is easy to operate. This is the main objective of the present invention.

(Means for Solving the Problems) As a result of intensive research in accordance with the above object, the present inventors used a hollow fiber-like fully porous material as a carrier and added anionic groups at least near the surface of the structure portion of the porous material. We discovered that by introducing this method, there was no blood coagulation even when whole blood was directly processed, there was little loss of platelets, and low-density riboproteins could be selectively adsorbed. The present inventors have discovered that the adsorption ability of low-density riboproteins can be further improved by introducing anionic groups near the surface of the structure and at the same time introducing anionic groups far from the structure, leading to the present invention. .

That is, the present invention is an adsorbent for body fluid treatment characterized by having an anionic group at least near the surface of the structure portion of the hollow fiber-like fully porous body; This is an adsorbent for body fluid treatment characterized by having an anionic group near the surface of the structure part and also having anionic groups far from the structure part.

Conventionally, when using adsorbents to adsorb low-density riboproteins, which have very large molecules, substances with long chain structures such as heparin and dextran sulfate that interact with low-density riboproteins were used as ligands. Therefore, it is thought that adsorption cannot occur unless the ligand is extended sufficiently far from the carrier surface.In fact, when using a porous gel as a carrier, even if a short molecule is used as the ligand,
It was not possible to sufficiently adsorb low-density riboproteins. In contrast, the present inventors surprisingly found that by using a hollow fiber-like fully porous material as a carrier, a sufficient amount of low-density riboprotein could be adsorbed even when a short molecule was used as a ligand. . It is not clear why short molecules can adsorb low-density riboproteins efficiently, but
Adsorbents with short molecules bound have the advantage that the molecules themselves have low antigenicity and the ligand bond is difficult to break during sterilization.1. This fact is revolutionary as an adsorbent. Furthermore, if you combine short and long molecules,
Low-density riboproteins can be adsorbed by short molecules near the walls of the structure of the hollow fiber-like fully porous material, and by long molecules in the micropore spaces, making it possible to adsorb low-density riboproteins with extremely high efficiency. Become.

In the present invention, a hollow fiber-like fully porous body has a hollow fiber-like appearance, and the microstructure of the hollow fiber structure portion (hereinafter referred to as a membrane) substantially has a porous structure that communicates from the inner surface to the outer surface of the membrane. Say what you have on the entire top.

The pore size of the membrane can be freely selected depending on the size and shape of the adsorbed substance, but the pore size must be such that the adsorbed substance can freely pass through.
In addition, it is desirable that there be a sufficient surface area with which the adsorbed substance can come into contact. When the average pore diameter is defined as the pore diameter that indicates a pore volume of 172 of the total pore volume on the pore diameter-pore volume integral curve determined by a mercury porosimeter, the average pore diameter of the hollow fiber-like fully porous body used in the present invention is 0.005μm to 3
It is preferably in the μm range, and can be selected depending on the size of the substance to be adsorbed. A more preferable average pore diameter is 0.01 μm
The range is from 0.02 μm to 2 μm, and preferably from 0.02 μm to ltlm. When the pore surface area of the porous structure of the membrane is defined as the value determined from the amount of nitrogen adsorbed using a BET surface area measuring device, the pore surface area of the hollow fiber-like fully porous body used in the present invention is 5%/g. It is preferable that it is more than 10rrf/
It is more preferable that it is 15r+? /g or more is desirable. The inner diameter of the hollow fiber is preferably 30 μm or more, more preferably 50 μm to 5 mm, and desirably 100 μm to 1 mm. The thickness of the hollow fibers is preferably 5 μm or more, more preferably 10 μm to 100 μm, and desirably 20 μm to 500 μm.

As the material for the hollow fibers, any of hydrophilic materials such as cellulose, cellulose derivatives, polyvinyl alcohol, and ethylene-vinyl alcohol copolymers, and hydrophobic materials such as polyethylene, polypropylene, polysulfone, and polytetrafluoroethylene can be used. In the case of hydrophobic materials, since it is difficult to filter aqueous liquids, it is preferable to perform a hydrophilic treatment by coating the surface with a hydrophilic material, making the surface hydrophilic by chemical treatment, making the surface hydrophilic by plasma treatment, or the like. In addition, in order to introduce an anionic group, for example, when a ligand having an anionic group is immobilized, a hydroxyl group, an amino group, a carboxyl group, which can easily immobilize a ligand having an anionic group on the surface of the hollow fiber-like fully porous material, It is preferable that it has a functional group such as a thiol group, but even if it does not have such a functional group, it can be prepared by a method such as plasma treatment or embedding coating with a ligand having an anionic group. Ligands can be immobilized.

All known methods such as covalent bonding, ionic bonding, physical adsorption, embedding, and insolubilization by precipitation on the membrane surface can be used to immobilize a ligand having an anionic group on the surface of the hollow fiber-like fully porous material. In view of the elution properties of a ligand having a functional group, it is preferable to immobilize and insolubilize the ligand by covalent bonding. For example, immobilized enzymes, known carrier activation methods used in affinity chromatography, and immobilization methods can be used. Examples of activation methods include cyanogen halide method, periodic acid method, crosslinking reagent method, and epoxide method. The activation method involves modifying the surface of the hollow fiber-like fully porous material to make it highly reactive, and then performing a nucleophilic reaction with active hydrogen such as amino groups, hydroxyl groups, carboxyl groups, thiol groups, etc. of ligands with anionic groups. It is sufficient that it can undergo a substitution and/or addition reaction with the group, and is not limited to the above examples.

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

In the present invention, anionic groups refer to functional groups that exhibit a negative charge in body fluids, such as sulfonic acid groups, sulfuric acid groups, phosphoric acid groups, and carboxyl groups.

Furthermore, in the present invention, the term "near the surface" refers to a space from the surface of the structure part (the material itself) constituting the hollow fiber-like fully porous body up to 200 people, and includes the surface of the structure. This distance corresponds to the diameter of low density riboprotein.

The method of introducing an anionic group near the surface of the structural part of a hollow fiber-like fully porous material is to introduce a low-molecular compound having an anionic group onto the surface of the structural part of the hollow fiber-like fully porous material by covalent bonding or ionic bonding. In the case of a polymeric compound with anionic groups, it can be bonded by coating on the surface of the structural part of the hollow fiber-like fully porous body. Examples include a method of manufacturing using a compound that has

Since low-density riboprotein has cationic amino acid residues on its surface, it electrostatically interacts with anionic groups present on the surface of the hollow fiber-like fully porous structure.
It is attracted by electrostatic attraction.

In addition to low-density riboproteins, proteins, peptides, and viruses that have cationic domains on their surfaces, such as activated complement components C3a, C4a, and C5a, and certain retroviruses can also be adsorbed to the adsorbent of the present invention. be done.

In claim 2 of the present invention, the meaning of having an anionic group even at a distance of the structure part means that the anionic group is present in a space 200 Å or more away from the surface of the structure part constituting the hollow fiber-like fully porous body. It means to have.

A method for introducing an anionic group into a remote part of the structural part of a hollow fiber-like fully porous body is to bond a preferably chain-shaped polymer compound having an anionic group to the surface of the structural part of the hollow fiber-like fully porous body. method, and a method of extending a graft chain having an anionic group from the surface of the structure portion of a hollow fiber-like fully porous body.

The molecular weight of the polymer compound having an anionic group (hereinafter referred to as 1, polyanion) is preferably 600 to 10', and 1
000 to 5×106 is more preferable, and 2000 to 10h is more preferable.

Examples of polyanions include vinyl-based synthetic polyanions such as polyacrylic acid, polymethacrylic acid, polyvinyl sulfonic acid, polyvinyl sulfate, polymaleic acid, polyfumaric acid, and derivatives thereof, and styrene-based synthetic polyanions such as polystyrene sulfonic acid and polystyrene phosphoric acid. Examples of polyanions include polyglutamic acid, polyaspartic acid, etc.; examples of nucleic acid polyanions include polyU, polyA, etc.; examples of synthetic polyanions include polyphosphoric acid ester, polyα-methylstyrene sulfonic acid, Examples include styrene-methacrylic acid copolymer, and polysaccharide polyanions include heparin, dextran sulfate, chondroitin sulfate, alginic acid, pectin, hyaluronic acid, and derivatives thereof. The polyanion referred to in the present invention is not limited to the above-mentioned examples.

By providing anionic groups both near and far from the surface of the hollow fiber-like fully porous body, low-density riboproteins can be adsorbed both on the surface of the hollow fiber-like fully porous body and in the spaces between micropores. As a result, the amount of low-density riboproteins adsorbed per unit volume increases dramatically, making it possible to adsorb low-density lipoproteins with high efficiency.

Further preferable results can be obtained by subjecting the inner surface of the adsorbent for body fluid treatment of the present invention to treatments for inhibiting platelet adhesion and blood coagulation.

The adsorbents for body fluid treatment described above are concentrated in large numbers,
The material with both ends adhesively fixed is filled in a container, and is used as a body fluid treatment adsorbent having a structure in which the outside of the container and the inner surface of the body fluid treatment adsorbent are in communication. In other words, the patient's body fluid was introduced into the inner surface of the body fluid processing adsorbent of the body fluid processing adsorbent, and the adsorbed substance that moved from the inner surface of the body fluid processing adsorbent to the membrane (hollow system structure part) was fixed on the membrane. It interacts with anionic groups and is adsorbed, and the unadsorbed body fluid components are also used as an adsorbent suitable for use in being led out of the container.

In addition, in order to make it easier for adsorbed substances to move to the membrane, a structure is provided in which the outside of the container communicates with the outer surface of the adsorbent for body fluid treatment, making it easier for body fluids to move from the inner surface of the hollow fiber to the outer surface. structure.

Hereinafter, the present invention will be explained using 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, and FIG. 2 is a schematic diagram showing another example. FIG. 3 is a schematic diagram showing the presence of anionic groups in the micropores of the adsorbent for body fluid treatment of the present invention.

In FIG. 1, body fluid is introduced from a body fluid inlet 1 and sent to a body fluid treatment adsorption device 3 by a body fluid transport means 2. In the absorber 3 for body fluid treatment, the body fluid is sent to the inner surface of the absorbent material 4 for body fluid treatment, and the liquid component permeates into the membrane (porous structure) from the inner surface, and some of the liquid components are used for body fluid treatment. It migrates to the outer surface of the adsorbent 4, returns to the inner surface of the adsorbent 4 for body fluid treatment, and merges with the body fluid. In this process, the adsorbed substance (low-density lipoprotein, etc.) is adsorbed to the anionic group fixed to the membrane of the adsorbent for body fluid treatment, and the body fluid with the adsorbed substance adsorbed is led out from the body fluid outlet 5. Ru.

Figure 3 schematically shows the presence of anionic groups in the micropores of the adsorbent for body fluid treatment. The structure shown in FIG. 3 has anionic groups 8 near the surface 7 and also in the far region 9 of the structure portion 6. When the substance to be adsorbed (low-density lipoprotein, etc.) passes through the micropores, it interacts with the anionic groups within the micropores and is adsorbed.

FIG. 2 is a schematic cross-sectional view showing another example of an adsorption device using the adsorbent for body fluid treatment of the present invention.
The body fluid transport means 2 sends the body fluid to the adsorption device 3 for body fluid treatment. In the adsorbent 3 for body fluid treatment, body fluid is sent to the inner surface of the adsorbent 4 for body fluid treatment, and liquid components are sent from the inner surface through the membrane to the outer surface of the adsorbent 4 for body fluid treatment. During this process, the substance to be adsorbed (low-density lipoprotein, etc.) interacts with anionic groups in the membrane and is adsorbed. The liquid component from which the adsorbed substance has been adsorbed and removed is sent in the direction of the body fluid outlet 5 by the liquid component transport means 10, merges with the body fluid, and then is led out from the body fluid outlet 5.

The adsorbent for body fluid treatment of the present invention has been described above, and the present invention will be explained in more detail below with reference to Examples.

(Example) Example 1 As a hollow fiber-like fully porous body, poly2-hydroxyethyl methacrylate (polyHEMA) was added to polyethylene hollow fibers.
) was coated and thermally crosslinked. Polyethylene hollow fiber has an inner diameter of 340 μm, an outer diameter of 440 μm, and a film thickness of 50 μm.
m, an average pore diameter of 0.3 μm, and a surface area of 21 rrr/g. PolyHEMA was prepared by adding 100 g of 2-hydroxyethyl methacrylate, 640 g of ethanol, and 0.4 g of abbisisobutyronitrile, and then heating at 57°C for 7 hours.
The polymer was polymerized with stirring for 5 hours, precipitated in water, and purified. PolyH for polyethylene hollow fibers
For the EMA coating, polyethylene hollow fibers were immersed in a 2% by weight ethanol solution of polyHEMA, left at 40°C for 10 minutes, taken out, and dried at 50°C for 1 hour.

The obtained hollow fibers were bundled, and both ends were fixed with silicone adhesive to form a bundle of 50 hollow fibers with an effective length of 15 cm. Both ends were fixed to prevent the hollow fibers from shrinking and heated at 120°C for 3.
Heat crosslinked for a time.

Next, epoxy groups were introduced into the hollow fiber-like fully porous body.

The method was as follows: First, 80 ml of dimethyl sulfoxide, 40% by weight of sodium hydroxide, 30 ml of epibromohydrin BOd,
A mixed solution of g was prepared and flowed inside the hollow fibers of the hollow fiber-like fully porous body at a flow rate of 2.4 min/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. The reaction was continued in this state for 5 hours, and then washed with acetone and water.

After this, taurine was immobilized on the hollow fiber-like fully porous body into which epoxy groups were introduced. The method is to first add 0.1g of taurine to 0.
．． 1M sodium carbonate buffer (pH 9,8) 100
After dissolving in d, 2.4% /
It was flowed at a flow rate of min.

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.

The mixture was allowed to react in this state for 16 hours, and then washed with water to obtain an adsorbent for body fluid purification on which taurine was fixed.

According to the manufacturing method of this adsorbent, the position where the anionic group (sulfonic acid group of taurine) exists is in the vicinity of the structure part of the hollow fiber-like fully porous material (200 minutes from the surface of the structure part).
within one person). The amount of taurine fixed was 60 μequivalent per ml of the volume of the porous portion of the hollow fiber-like fully porous body.

After drying the adsorbent for body fluid treatment obtained as described above, both ends are fixed with urethane adsorbent in a tubular container,
After cutting both ends, a nozzle was formed, and an adsorption device for body fluid treatment as shown in FIG. 4 was manufactured. The effective length of the adsorbent for body fluid treatment was 7.5 cm, and the number of adsorbents was 50. In Figure 4, is 11 the body? fi is an inlet side nozzle, 12 is a blood outlet side nozzle, 4 is an adsorbent for body fluid treatment, and 13 is a nozzle for extracting liquid components.

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

Heparinized whole blood from a patient with familial hypercholesterolemia was introduced through body fluid outlet l, and pump 2 was used to
It was sent to the adsorption device 3 for body fluid treatment within minutes.

Plasma, which is a liquid component, is filtered using the adsorbent material 4 for body fluid treatment, and the plasma is sent toward the body fluid outlet using the pump 10, where it is combined with blood rich in blood cells derived from the body fluid treatment adsorption device 3, and the blood plasma is extracted from the body fluid. It was taken out from outlet 5. The flow rate of pump 10 was set to 115 times the flow rate of pump 2, and in this state, 67 whole blood was recirculated for 30 minutes.

No blood coagulation or hemolysis was observed during circulation, and stable circulation was achieved. Total cholesterol in blood (plasma) before and after treatment was measured by an enzymatic method. In the blood of patients with familial hypercholesterolemia, most of the cholesterol is derived from low-density riboproteins.

As a result, the total cholesterol was 510 μ/d before treatment, but it decreased to 190 μ/d after treatment.

Comparative Example 1 Taurine was immobilized using CNBr-activated Sepharose 4B [Pharmacia Japan Co., Ltd.], which is an agarose-based fully porous spherical gel, instead of using a hollow fiber-like fully porous material. Taurine was immobilized on CNBr-activated Sepharose 4B in accordance with the usual method recommended by Pharmacia. The amount of taurine fixed was 50 μeq/-(wet volume).

Comparative Example 1 Taurine-immobilized Sepharose 4B with the same volume of porous structure part as the volume of the porous structure part of the absorber for body fluid treatment of Example 1 was added to the same blood 6d used in Example 1. , and incubated for 30 minutes with shaking. As a result, the total cholesterol before treatment was 510
■/d1 tare, but after processing 450■/di
It didn't go down much.

Example 2 The same hollow fiber-like fully porous material as in Example 1 was used, and the method of introducing epoxy groups into the hollow fiber-like fully porous material was also carried out.
The same procedure as in Example 1 was carried out.

In order to introduce anionic groups, dextran sulfate with a molecular weight of N50,000 and taurine were reacted with the hollow fiber-like fully porous material after the introduction of epoxy groups. The method of introduction is as follows: First, prepare a 0.1% by weight aqueous dextran sulfuric acid solution whose pH is adjusted to 13 with sodium hydroxide, bring this to a temperature of 50°C, and raise the temperature to 0.1% by weight.
The mixture was flowed inside the hollow fibers of the hollow fiber-like fully porous body after the introduction of epoxy groups at a flow rate of 24% per 1 hour, and circulated for 1 hour. At this time, the flow rate of the filtrate was not adjusted. Next, the hollow fiber-like fully porous material was washed with water, and then 0.1 g of taurine was added to the
A solution dissolved in sodium carbonate buffer (pH 9, 8) was prepared, poured into the inside of the hollow fibers of the hollow fiber-like fully porous body, and circulated for 15 hours.

The temperature of the taurine solution at this time was 50°C, and the flow rate of the filtrate was not controlled. Thereafter, it was washed with water and dried to obtain an adsorbent for body fluid treatment. According to the above manufacturing method, anionic groups mainly derived from taurine exist in the vicinity of the structural part of the hollow fiber-like fully porous material, and anionic groups derived from dextran sulfate exist far from the structural part. .

The adsorbent for body fluid treatment obtained by the method described above was used as an adsorbent in the same manner as in Example 1, and an adsorption experiment was conducted in the same manner as in Example 1. As a result, the cholesterol concentration before treatment was 51
0■/d1, but after treatment it was 90■/d1
It was down to .

Example 3 The same polyethylene hollow fibers as in Example 1 coated with a copolymer of ethylene and acrylic acid were used as an adsorbent for body fluid purification. The ethylene-acrylic acid copolymer was polymerized using azobisisobutyronitrile as an initiator, and this was coated on polyethylene at a concentration of 2%, and after drying, it was used as an adsorbent for body fluid purification. Acrylic acid 7mer
The molar ratio of azobisisobutyronitrile and ethylene monomer was set to 3 nia, and the molar ratio of azobisisobutyronitrile to the monomer was set to 1/200.

According to the above manufacturing method, the anionic group exists near the structural part of the hollow fiber-like fully porous body.

The adsorbent for body fluid treatment obtained by the method described above was used as an adsorbent in the same manner as in Example 1, and an adsorption experiment was conducted in the same manner as in Example 1. As a result, the cholesterol concentration before treatment was 51
0■/d, but after treatment it was 240■/d1
It was down to .

(Effects of the Invention) As described above, by using the adsorbent for treating body fluids of the present invention, substances that interact with anionic groups from body fluids can be adsorbed with low antigenicity and are easy to sterilize. We were able to create a stable adsorbent. Furthermore, as a result of having a very high adsorption capacity as an adsorbent, it has become possible to efficiently adsorb the adsorbed substance with a small priming volume.

The adsorbent for body fluid treatment of the present invention is particularly suitable for malignant substances that are expressed in body fluids and are thought to be closely related to the cause or progression of diseases, such as low-density lipoproteins, anaphylatoxins, and retroviruses. It is particularly useful for adsorption and removal of substances that interact with anionic groups.

[Brief explanation of the drawing]

FIG. 1 is a schematic diagram showing an example of an adsorption device using the adsorbent for treating body fluids of the present invention, FIG. 2 is a schematic diagram showing another example of an adsorption device using the adsorbent for treating body fluids of the present invention, and FIG. Figures A and 3 are schematic diagrams showing the presence of anionic groups in the micropores of the adsorbent for treating body fluids of the present invention, and Figure 4 shows an example of an adsorption device using the adsorbent for treating body fluids of the present invention. It is a schematic diagram. l ・ 2 ・ 3 ・ 4 ・ 5 ・ 6 ・ 7 ・ 8 ・ 9 ・ 10 ・ 11 ・ 12 ・ 13 Body fluid inlet Body fluid transport means (pump) Adsorbent for body fluid treatment Adsorbent material for body fluid treatment Body fluid outlet Hollow filament Fully porous body structure part Surface of the structure part Anionic group Distance liquid component transport means (pump) of the structure part Body fluid inlet side nozzle Body fluid outlet side nozzle Liquid component outlet nozzle Figure 1 Figure 3 Figure 2 figure

Claims (2)

[Claims] (1) An adsorbent for body fluid treatment characterized by having an anionic group at least near the surface of the structure portion of a hollow fiber-like fully porous body. (2) An adsorbent for body fluid treatment characterized by having an anionic group near the surface of the structure part of a hollow fiber-like fully porous body and also having anionic groups far from the structure part.