JPH06296861A - Bradykinin adsorbent - Google Patents

Abstract

PURPOSE:To obtain a bradykinin adsorbent capable of adsorbing bradykinin selectively almost without removing useful substance such as albumin or immunoglobulin to ensure safe external circulation by forming the absorbent out of a non-water soluble porous element with a carbonized surface. CONSTITUTION:The subject bradykinin adsorbent is formed out of a non-water soluble porous element with a carbonized surface, and is generally used by being filled in a container with an inlet/outlet for a body fluid and maintained in it. One example of an adsorption vessel 1 filled with the absorbent is shown in the drawing. A cap 6 with a body fluid inlet 5 is screwed into an opening on one end of a cylinder 2 through a packing 4 in which a filter 3 is spread. Further, a cap 8 with a body fluid introduction outlet 7 is screwed into an opening on the other end of the cylinder 2 through a packing 4' in which a filter 3' is spread, thus forming a container. The bradykinin adsorbent is filled and held in a clearance between the filters 3, 3' to form a bradykinin adsorbent layer 9.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a bradykinin adsorbent that selectively adsorbs bradykinin, which is believed to be closely related to certain anaphylactic symptoms.

[0002]

2. Description of the Related Art In recent years, with the development of medical materials and medical techniques, blood purification therapy for removing waste products and pathogenic substances in blood by extracorporeal circulation has been clinically used. This blood purification by extracorporeal circulation is very useful clinically, but on the other hand, some patients have anaphylactoid symptoms such as hypotension and dizziness, which may be due to elevated bradykinin during or after circulation. Was found as a result of the study by the present inventors. Therefore, a technique for selectively removing bradykinin from blood is desired. However, there is no adsorbent usable for the above purpose.

[0003]

As described above, there has been no adsorbent for anaphylactoid symptoms caused by an increase in bradykinin, and there has been a demand for urgent development. The purpose of the present invention is to provide a safer extracorporeal circulation with albumin,
An object of the present invention is to provide an adsorbent capable of selectively adsorbing and removing bradykinin by removing almost no useful substance such as immunoglobulin.

[0004]

Means for Solving the Problems As a result of intensive studies conducted by the present inventors in view of the above-mentioned object, the use of a water-insoluble porous material having a carbonized surface such as activated carbon results in a surprisingly high rate. Furthermore, they have found that they can selectively adsorb bradykinin, and have completed the present invention. That is, the gist of the invention resides in a bradykinin adsorbent (hereinafter simply referred to as the present adsorbent) characterized by comprising a water-insoluble porous material having a carbonized surface.

The bradykinin targeted by this adsorbent will be described in more detail. It is a basic peptide having a molecular weight of about 1.0 × 10 ³ and is used for smooth muscle contraction, vasodilation, and capillary permeability enhancement. Have an effect. It is also involved in the development of anaphylactic symptoms and other inflammatory effects. Bradykinin production in plasma is due to activated kallikrein acting on the polymeric kininogen to release bradykinin from the polymeric kininogen. The activation of kallikrein is due to the fact that factor XII, which is a blood coagulation factor, is activated by contacting the foreign surface, particularly the negatively charged surface, and the activated factor XII activates kallikrein. That is, it can be said that the increase in bradykinin in plasma occurs due to the contact of factor XII with the foreign surface. In addition, kallikrein enhances bradykinin elevation by positively feeding back and further activating factor XII. Glass, celite, kaolin, collagen and the like have long been known as substances that activate factor XII. In addition, it is known that it is activated by stearic acid, ellagic acid, sulfatide, plasmin, kallikrein and the like. In addition, according to the research conducted by the present inventors, it was found that contact with a surface of a medical material having many negative charges activates factor XII, which causes an increase in bradykin.

Bradykinin produced by activation of factor XII in plasma is inactivated by kininase, which is a bradykinin inactivating enzyme, and thus does not usually cause a serious problem. However, according to the study by the present inventors, it was found that anaphylactoid symptoms such as nausea and hypotension appear when the plasma bradykinin concentration is 4000 pg / ml or more. Therefore, when the bradykinin concentration in plasma is increased due to extracorporeal circulation or the like, it is necessary to maintain the produced bradykinin concentration at 4000 pg / ml or less or remove it. For safer extracorporeal circulation, 3000 pg / ml or less, most preferably 1000
It was to keep below pg / ml or to remove.

The water-insoluble porous material having a carbonized surface as used in the present invention means a substance which is solid in water, has a contact angle of 20 degrees or more, and whose surface is carbonized like activated carbon. The "contact angle" referred to here is the contact angle of air bubbles on the solid surface in water. This contact angle is measured by directly projecting the shape of a small droplet placed on the solid surface onto the screen, or by measuring the volume, height, radius of the bottom circle, etc. of the droplet. There is a method of calculating as a part of the sphere by calculation, a tilt angle when tilting the solid volume from the vertical position so that the curved portion of the liquid surface contacting the solid becomes a horizontal plane, and a measurement of adhesion tension. In the present invention, the "contact angle" is
W. C. Hamilton. J. Colloid In
terface Sci. ． 40.219-222 (1
972) and J. D. Andrade. J. Poly
m. Sci. Polym. Symp. ． 66.313-
336 (1979) refers to the measured contact angle according to the principle and method. Further, as the sample, a molded product such as a sheet or a film was prepared, the temperature condition of the contact angle was 25 degrees, the measurement was performed 10 times or more, and the average value was used as the value of the contact angle of the material.

As the shape of the water-insoluble porous material having the activated carbon surface, any of spherical shape, granular shape, thread shape, hollow fiber shape, flat membrane shape and the like can be effectively used, but it is spherical or granular depending on the flow rate of the body fluid volume in the body fluid circulation. Is most preferably used. If the average particle size of the spherical or granular particles is less than 10 μm, the body fluid in the body fluid circulation tends to stagnate, which is not preferable. Also, 25
When it exceeds 00 μm, the contact time between the body fluid and the present adsorbent is shortened and the adsorbability is lowered, which is not preferable. Therefore, 1
It is preferably from 0 to 2500 μm, further from 25 μm to 1
The range of 000 μm is preferable, and particularly 50 μm to 600 μm.
The range of m is the most preferable.

The water-insoluble porous material having a carbonized surface is required to be a porous material from the viewpoint that a large adsorption surface for bradykinin can be obtained and a practical adsorption ability can be obtained. The exclusion limit molecular weight based on the protein of the porous body may be at least the molecular weight of bradykinin to be adsorbed. If specifically shown, the range of 2 × 10 ² to 2 × 10 ⁷ is preferable. More preferably, it is 2 × 10 ² to 2 × 10 ⁴ .

Methods for measuring the surface area of the porous body include physical adsorption method, immersion heat method, permeation method, and chemical adsorption method. However, since the pore diameter of the porous body and the surface area for each pore diameter can be obtained, mercury injection is performed. The method is useful (Catalyst Engineering Course-4, “Catalyst Measurement Method” published by The Institute of Catalysts, Jijijinshokan, pages 69-73). According to the study by the present inventors, since bradykinin is a protein having a small molecular weight among blood liquid components, it was found that the pore size on the adsorbent to be adsorbed is greatly different from that of other blood liquid components. . In other words, if the pore size exceeds 5000Å,
Since other blood liquid components easily enter the pores and hinder the entry of bradykinin into the pores, the adsorption performance of the adsorbent is significantly reduced. Therefore, it was found that the adsorbability of bradykinin can be improved by reducing the pore size on the adsorbent. The smaller it is, the higher the adsorption property of the adsorbent to bradykinin becomes, but if it is less than 5 Å, it is difficult to enter into the pores, which is unsuitable as an adsorbent. Therefore, a suitable pore size for a bradykinin adsorbent is 5000Å
It is preferable that the pores are gathered in the range from 5 to 5Å,
More preferably, it is in the range of 2000Å to 20Å,
Most preferably, it is in the range of 50Å to 500Å.

Further, according to the study by the present inventors, if the total surface area per unit adsorbent is less than 10 m ² / ml, the contact area between bradykinin and the adsorbent is small, and the adsorbing ability cannot be sufficiently exhibited, which is not preferable. Therefore, the total surface area is 10
It is preferably m ² / ml or more, more preferably 2
0m ² / ml or more, the most preferable range is 40m ²
/ Ml or more.

Activated carbon generally has a molecular weight of 10
It is a typical example of a water-insoluble porous material having a surface of activated carbon used for adsorption of substances of ⁴ or less, but it is powdery, granular (crushed), spherical, fibrous, cloth-like (woven cloth-like) depending on its manufacturing method. ,
Non-woven fabric), plate-shaped objects, etc. Also, the pore distribution is distributed in the smaller pores, in the larger pores, and in the small and large areas. There are various types such as The activated carbon preferably has a granular shape, and the pore distribution is large in the preferable pore size range. To explain this pore distribution in more detail, it is preferable that the pores having a pore diameter of 20 to 2000Å account for 40% or more of the whole, and most preferably the pores for 50 to 500Å account for 60%.

As a method for producing activated carbon, carbon dioxide,
Activated gas such as air and combustion gas and high temperature (750-10
Generally, a gas activation method in which a catalytic reaction is performed at 50 ° C.) for activation and a chemical activation method using a chemical such as zinc chloride or phosphoric acid are often used. In addition, there are a method of activating charcoal and the like with steam, and a method of forming and activating beads made from petroleum pitch. The activated carbon of the present adsorbent can be produced by such a generally used method. Also, 1
By performing the steam activation method under the condition of exceeding 100 ° C., it is possible to manufacture an adsorbent in which only the outer surfaces of the carbon particles are activated and the inside is not activated. As the adsorbent of the present invention, it is sufficient that the contact site with bradykinin is activated, and the adsorbent obtained by this method can also be used.

The adsorbent of the present invention may be a water-insoluble porous body having a carbonized surface, which is hydrophilic and has a coating layer capable of suppressing the adhesion of platelets in order to improve the affinity with blood. good. According to the study of the present inventors, the coating layer is hardly formed or formed on the inner wall surface of the fine pores, which are considered to contribute most to the adsorption of bradykinin, in the porous portion of the adsorbent of the present invention. However, it becomes an extremely thin layer. Therefore, even after the coating treatment, the adsorbent of the present invention always has an exposed carbonized surface centering on the inner wall surface of the fine pores, and these exposed surfaces exhibit bradykinin adsorbing ability. Moreover, since the micropores having these exposed surfaces have small pores and blood cell components such as platelets cannot enter, there is no problem in blood compatibility even if they are not covered. On the other hand, the inner wall surface of the pores having a relatively large pore size and the surface of other adsorbents are sufficiently covered with the coating, so that invasion and adhesion of platelets can be almost completely prevented. The hydrophilic coating layer has an original purpose of improving blood compatibility, and an index that objectively indicates the degree of blood compatibility is necessary, but it is difficult to stably obtain blood and there is a difference between blood. Therefore, it is difficult to make a common and stable evaluation. Regarding the degree of hydrophilicity, it is preferable that the contact angle at 25 ° C. of air bubbles on the solid surface in sheet form or film form in water is 20 ° or more.

The hydrophilic coating layer is preferably a polymer in order to prevent peeling during use. Specific examples of the hydrophilic coating layer include 2-hydroxyethyl acrylate, 2-hydroxypropyl acrylate, 2-hydroxyethyl methacrylate, and 2-hydroxypropyl. Methacrylate, 2
-Hydroxybutyl methacrylate, N, N-diethylaminoethyl methacrylate, dimethylaminoethyl methacrylate, methoxydiethylene glycol methacrylate, methoxytriethylene glycol methacrylate, glycerol monoacrylate, glycerol monomethacrylate, acrylic acid or methacrylic acid and its derivatives, methoxytriethylene Methoxypolyethylene glycols such as glycols, polyethylene glycols, styrene derivatives such as diethylaminoethylstyrene, hydroxystyrene and hydroxymethylstyrene, vinylamine, monomers having a vinyl group such as vinyl alcohol, (segmented) polyurethane, ( Segmented) Polyester, Mono (2-methacryloyloxyethyl) Head phosphate, mono (2-acryloyloxyethyl) acid phosphate and the like polymers containing any one or more of monomers, block copolymers, graft copolymers and the like. In particular, it is preferable that the polymer has a hydroxyl group. There is no particular limitation on the bonding mode of the hydroxyl group in the copolymer. Further, it is preferable to use a copolymer containing methacrylic acid or 2-dimethylaminoethyl methacrylate for the coating layer of the present adsorbent, since it is difficult to elute in water.
Further, a crosslinkable monomer such as glycidyl methacrylate may coexist and be crosslinked.

The polymer may be a homopolymer of the above-mentioned polymer monomers, or may be a copolymer of two or more. Further, it may be a copolymer with a polymer unit having a hydroxyl group containing 0.1 to 20% by weight of a polymer unit having a basic functional group. These polymers are not particularly related to the polymerization form such as linear polymers, graft polymers and crosslinked polymers. The molecular weight of the polymer is 1000 in order to prevent peeling due to long-term storage during use or after formation of the coating layer.
The following are not preferred: Further, since the solubility of the polymer in a solvent decreases when the molecular weight is 100,000 or more, the molecular weight of 100,000 or more is not preferable. Therefore, the molecular weight of the polymer is preferably in the range of 1,000 to 100,000, more preferably 1,000 to 50,000.
And particularly preferably 5000 to 5000
The range is 0.

The polymer coating layer may be formed by a grafting method or a precipitation method,
It may be obtained by any method such as a coating method or a covalent bonding method utilizing a functional group on the surface of the porous body. Among them, the coating method is particularly preferable for practical use because the manufacturing operation is easy.

The adsorbent of the present invention is generally used by being filled and held in an easily equipped body with a body fluid outlet. An example of an adsorber (1) filled with the present adsorbent is shown in FIG. A cap (6) having a body fluid introduction port (5) is screwed into one end opening of the cylinder (2) through a packing (4) having a filter (3) stretched inside the cylinder (2). At the other end opening, a bodily fluid introduction / outlet (7) is provided through a packing (4 ') with a filter (3') inside.
Forming a container by screw-fitting a cap (8) having
An adsorbent layer (9) is formed by filling and holding an adsorbent in the gap between the filters (3) and (3 ').

According to the study by the present inventors, the adsorbent layer (9) may be filled with the present adsorbent alone, or may be mixed with another adsorbent or laminated on the body fluid outlet side. Is also good. The capacity of the adsorbent layer (9) is 1 when used for extracorporeal circulation.
About 0 to 500 ml is suitable. When this adsorbent is used to adsorb and remove the increased bradykinin due to extracorporeal circulation, it can be roughly classified into two methods. One is a method applied to plasma that has been separated from whole blood in advance by a centrifugation method or a membrane separation method. As the method for separating plasma, the membrane separation method is preferable in terms of economy and the fact that blood cell components are not mixed. As shown in FIG. 2, the whole blood sent to the plasma separator (13) by the blood pump (14) is divided into a plasma component and a blood cell component. The separated plasma is sent to a medical material (11) other than the adsorbent by a plasma pump (12) to remove pathogenic substances and waste products. Purified plasma is sent to the adsorbent (10), and after removing bradykinin that has risen due to the surface contact of a medical material other than the adsorbent (10), it is returned to the body (15) together with blood cell components. The other one is a blood pump (1
By 4), it is sent to the medical material (11) other than the present adsorbent to remove pathogenic substances and waste products. The purified blood is sent to the adsorbent (10) to remove bradykinin that has risen due to the surface contact of a medical material other than the adsorbent, and then returned to the body. There is almost no difference in bradykinin adsorption capacity between these two methods. Therefore, the method may be selected according to the adsorption ability and removal ability of the medical material other than the present adsorbent. Since it adsorbs bradykinin generated by passing medical materials other than this adsorbent, after passing medical materials other than this adsorbent,
It may be at any position as long as it can be adsorbed and removed by the present adsorbent. However, according to the research conducted by the present inventors, it has been found that it takes a certain amount of time from the contact of the blood with the surface of the foreign substance until the peak of bradykinin is increased and the peak is reached. This time was approximately 5 to 15 minutes, although it varied depending on the material of the medical material. Therefore, there is a time lag of 5 minutes or more between the blood contact with the medical material other than the adsorbent and the blood entering the adsorbent.

Medical materials other than this adsorbent include blood purifiers, adsorbents, leukocyte removal filters using non-woven fabric,
Examples are dialysis membranes and filtered plasma separation membranes. Regarding the passage rate of blood or plasma, since the adsorption capacity of this adsorbent is extremely high, the particle size of this adsorbent can be made coarse, and the packing degree can be lowered, so the shape of the adsorbent layer cannot be determined. It is possible to give a high passing speed regardless of. For that reason,
A large amount of body fluid can be processed. The body fluid may be passed through continuously or intermittently depending on the clinical need or the condition of the equipment. Medical materials other than this adsorbent can be appropriately combined and used irrespective of the shape and the material, according to clinical needs.

[0021]

INDUSTRIAL APPLICABILITY The bradykinin adsorbent of the present invention efficiently and selectively adsorbs and removes bradykinin in body fluids in which bradykinin has increased due to extracorporeal circulation, and effectively suppresses anaphylactoid symptoms. INDUSTRIAL APPLICABILITY The present invention is applicable to general applications for purifying and regenerating body fluids such as blood and plasma. In addition, the adsorbent of the present invention can be used not only as a therapeutic device filled in a container but also as an affinity adsorbent for separating and purifying bradykinin.

[0022]

Example 1 Petroleum pitch-based spherical activated carbon (MZ-AZ, manufactured by Kureha Chemical Industry) was used as a "water-insoluble porous body having a carbonized surface". The physical properties of the activated carbon used are 980 m in total surface area.
^{2. The} average pore size was 50Å and the particle size was 200 μm. Using this "activated carbon" as an adsorbent, the following adsorption experiment was conducted. Purified bradykinin (manufactured by Backchem Co., bradykinin) was added to 5 ml of a solution prepared by using physiological saline to adjust the bradykinin concentration to 40,000 pg / ml, and 0.1 ml of "activated carbon" was added, and the mixture was shaken at 37 ° C for 2 hours. .
After that, "activated carbon" is precipitated, and only the supernatant is commercially available EI.
The residual bradykinin concentration was determined using an A kit (Dainippon Pharmaceutical Co., Ltd. Merkit A bradykinin). As a result of the adsorption experiment, the concentration of the original solution was 40,000 pg / ml, whereas the concentration after the adsorption was below the measurement detection limit (1,000 pg / ml or less). That is, 97.% of bradykinin in the test solution.
5% could be adsorbed.

[0023]

Example 2 The same experiment as in Example 1 was carried out using the activated carbon used in Example 1 which was coated with polyhydroxyethyl methacrylate to give a hydrophilic coating on the surface of activated carbon. For polyhydroxyethyl methacrylate, 60 g of hydroxyethyl methacrylate and 387 g of ethanol were placed in a flask, the temperature was adjusted to 57 ° C., and then 0.24 g of azobisisobutyronitrile was added to obtain 7.5
Polymerization was carried out with stirring for an hour. The coating of the polymer on the activated carbon was carried out by immersing the activated carbon in a 1 wt% ethanol solution of the polymer for 15 minutes, collecting the activated carbon, and drying with hot air. An adsorption experiment was conducted using this polymer-coated activated carbon. The result of the adsorption experiment is the original solution concentration of 40,000p.
With respect to g / ml, the concentration after adsorption was below the detection limit of measurement (1000 pg / ml or less). That is, 97.5% of bradykinin in the test solution could be adsorbed.

[0024]

Example 3 Purified bradykinin (manufactured by Backchem Co., bradykinin) was added to physiological saline at a bradykinin concentration of 40.
A preparation liquid was prepared at a concentration of 000 pg / ml. Polymer-coated activated carbon used in Example 2 1 m
After packing 1 in a mini-column, 5 ml of physiological saline was flowed at a flow rate of 0.06 ml / min to perform priming in the same manner as in practical use. A mini column packed with primed polymer coated activated carbon at a flow rate of 0.06 ml / min,
The test liquid prepared previously was poured. Mini column effluent 8 ml
Was collected and the bradykinin concentration was measured. As a result of the experiment, the concentration after adsorption was below the detection limit of measurement (1000 pg / ml or less) with respect to the original solution concentration of 40,000 pg / ml. That is, 97.5% of bradykinin in the test solution could be adsorbed.

[Brief description of drawings]

FIG. 1 is a schematic sectional view showing an example of the form of an adsorber using the bradykinin adsorbent of the present invention.

FIG. 2 is an explanatory view showing one embodiment for adsorbing bradykinin in plasma using the bradykinin adsorbent of the present invention.

FIG. 3 is an explanatory view showing one embodiment for adsorbing bradykinin in whole blood using the bradykinin adsorbent of the present invention.

[Explanation of symbols]

 1 Adsorber 2 Cylinder 3, 3'Filter 4, 4'Packing 5 Body fluid inlet 6 Cap 7 Body fluid inlet 8 Cap 9 Bradykinin adsorbent layer 10 Bradykinin adsorbent 11 Medical materials other than bradykinin adsorbent 12 Plasma pump 13 Plasma separation Vessel 14 blood pump 15 blood / plasma mixing unit

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[Procedure amendment]

[Submission date] May 27, 1993

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0011

[Correction method] Change

[Correction content]

Further, according to the studies by the present inventors, if the surface area per unit adsorbent is less than 10 m ² / g , the contact area between bradykinin and the adsorbent is small, and the adsorbing ability cannot be sufficiently exhibited, which is not preferable. Therefore, the total surface area is 10 m ^2.
/ G or more, more preferably 20 m ²
/ G or more, and the most preferable range is 40 m ² / g or more.

[Procedure Amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0018

[Correction method] Change

[Correction content]

The present adsorbent is a container having a body fluid outlet port.
It is generally used after being filled and held in the. Main suck
The adsorbent can be used satisfactorily either alone or mixed with other adsorbents.
In addition, the adsorbent and other adsorbents fill the lower layer side where blood flows.
You may fill it. Also, if filled alone, simply
May be used alone to adsorb bradykinin in
And absorb the bradykinin produced by other blood processors.
It can also be used downstream of other blood treatment devices for dressing.
Can . To give a concrete example of a blood processor,
Dialysis machine, blood component separation device, plasma component separation device, body fluid composition
Minute adsorber, leukopheresis, postoperative perfusion in cardiac surgery
A leukocyte remover from blood, a bone debris, etc.
Filler filter, a filter to prevent adsorbent debris from entering the body
However, it is not limited to this.
Not a blood processor that raises bradykinin
It can be used favorably . Adsorber filled with this adsorbent
Specific examples of how to use (hereinafter referred to as adsorber)
And the blood collection tube, chamber,
Lamp, roller clamp, drip chamber, blood
Pump tube, etc. Any one or more
Use an extracorporeal circuit or blood transfusion circuit
You can also The equipment installed in the circuit is limited to the above.
It is not fixed . In addition, blood processing is performed in the middle of the circuit.
Blood pump or liquid transfer pump or suction pump or
It is also possible to use by incorporating a pump such as a peristaltic pump.
Wear. Also, be sure to use it well even if the drop due to the dead weight of blood is used.
You can An example of an adsorber (1) filled with the present adsorbent is shown in FIG. A cap (6) having a body fluid introduction port (5) is screwed into one end opening of the cylinder (2) through a packing (4) having a filter (3) stretched inside the cylinder (2). At the other end opening, a bodily fluid introduction / outlet (7) is provided through a packing (4 ') with a filter (3') inside.
Forming a container by screw-fitting a cap (8) having
An adsorbent layer (9) is formed by filling and holding an adsorbent in the gap between the filters (3) and (3 ').

[Procedure 3]

[Document name to be amended] Statement

[Name of item to be corrected] 0022

[Correction method] Change

[Correction content]

[0022]

Example 1 Petroleum pitch-based spherical activated carbon (MZ-AZ, manufactured by Kureha Chemical Industry) was used as a "water-insoluble porous body having a carbonized surface". The physical properties of the activated carbon used have a surface area of 980 m ^2.
/ G , average pore size 50Å, and particle size 200 μm. Using this "activated carbon" as an adsorbent, the following adsorption experiment was conducted. Purified bradykinin (manufactured by Backchem Co., bradykinin) was added to 5 ml of a solution prepared by using physiological saline to adjust the bradykinin concentration to 40,000 pg / ml, and 0.1 ml of "activated carbon" was added, and the mixture was shaken at 37 ° C for 2 hours. .
After that, "activated carbon" is precipitated, and only the supernatant is commercially available EI.
The residual bradykinin concentration was determined using an A kit (Dainippon Pharmaceutical Co., Ltd. Merkit A bradykinin). As a result of the adsorption experiment, the concentration of the original solution was 40,000 pg / ml, whereas the concentration after the adsorption was below the measurement detection limit (1,000 pg / ml or less). That is, 97.% of bradykinin in the test solution.
5% could be adsorbed.

Claims (1)

[Claims] 1. A bradykinin adsorbent comprising a water-insoluble porous material having a carbonized surface.