JPH0724066A - Selective leucocyte trapper and leucocyte trapping apparatus - Google Patents

Abstract

PURPOSE:To make possible to trap leucocyte efficiently by suppressing the adhesion of blood platelet from the beginning by filling the trapping material within a designated range of density with a designated average particle diameter consisting of fiber or porous polymer with continuous pores having specific polyethyleneglycol chain. CONSTITUTION:The leucocyte trapper is filled at a density of 0.05-0.5g/cm<3> with the trapping material which has an average particle diameter of 1-30mum comprising fiber or porous high polymer with continuous pores having cationic groups and polyethyleneglycol chain in 2-15 repeating units on the surface. This trapper can be used as a trapping material for blood transfusion, and for extracorporeal circulation in leucocyte trapping in blood of an autoimmune disease patient of whole body erythematodes, multiple sclerosis, malignant joint rheumatism, etc., in leucocyte trapping from blood of a lekemia or cancer patient, in leucocyte trapping with a purpose of immune function lowering before transplanting and other than those, it can also be used successfully in leucocyte trapping in postoperative perfusion blood and in dust removal, such as bone fragment, etc., in postoperative blood recovery.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a leukocyte capturing device for selectively capturing leukocytes in blood and a leukocyte capturing device incorporating the leukocyte capturing device. More particularly, the present invention relates to a leukocyte trap and a leukocyte trap that efficiently capture leukocytes from leukocyte suspension containing leukocytes in whole blood, red blood cells, platelet concentrate or extracorporeal circulation.

[0002]

BACKGROUND ART In the field of blood transfusion, serious side effects such as headache, nausea, chills, non-hemolytic fever reaction, alloantigen-sensitized blood transfusion rejection (GVHD), and viral infection occur in the field of blood transfusion. Is known to do. In order to prevent this side effect, leukocytes are trapped in the transfused blood by a leukocyte trap and a device made of a trapping material such as a polyester non-woven fabric or a cotton surface. In addition, for the purpose of treatment of autoimmune diseases such as systemic lupus erythematosus, malignant rheumatoid arthritis, multiple sclerosis, leukemia and cancer, or for the purpose of reducing immune function before transplantation, blood using a leukocyte trap and device such as non-woven The white blood cells inside are captured. In the field of cardiac surgery, for example, attempts have been made to capture leukocytes from blood perfused after coronary artery bypass surgery. This is because the white blood cells are activated at the surgical site,
It releases superoxide (superoxide), and this superoxide damages the surgical site, so that leukocytes are to be captured and removed in advance.

[0003] Conventionally, there is known a leukocyte trap which has a porous polymeric material such as a non-woven fabric or a sponge as a leukocyte trapping material. In particular, JP-A-62-243561 is disclosed for the purpose of capturing a large amount of white blood cells. These leukocyte traps are required to have high leukocyte trapping ability. That is, from the viewpoint of miniaturization of the container size and minimization of the priming volume, the total amount of leukocytes captured per unit volume is large, and the reduction rate of leukocyte concentration at the inlet and outlet of the column (leukocyte capture rate) is high. There must be one configuration requirement included. In order to achieve these, in the leukocyte trap, the packing density of the trapping material in the container has been increased, the amount of trapping material has been increased, and the container shape has been devised. Not a thing. However, at the same time, it is necessary to minimize the adhesion of other blood cell components in blood, particularly platelets, which is a particularly useful component, and selectively capture only the main target white blood cells. Platelets have high adhesiveness, and when the packing density of the capturing material is increased and the amount of the capturing material is increased, the adhesive amount increases like white blood cells, and there is a limit to compatibility of both in the above method. Therefore, it is necessary to develop a more selective leukocyte trap.

Low permeability of platelets As shown in WO / 05812 and Japanese Patent Application Laid-Open No. 1-249063, in the conventional trapping material, charge is imparted to the surface of the trapping material,
Although a leukocyte trap that has been surface-modified to selectively trap leukocytes has been disclosed, it cannot be said that sufficient platelet permeability can be achieved even with this technique.
Further, in JP-A-4-187206, an ethylene glycol chain is grafted on the surface to improve the passage of platelets, but the initial platelet adhesion is large and therefore not practically satisfactory.

Column shape Japanese Patent Laid-Open No. 62-243561 discloses a leukocyte trap for treating a large amount of blood. However, according to the research conducted by the present inventors, the leukocyte trapping ability is not satisfactory. Moreover, the platelet passage rate at the start is not satisfactory.

[0006]

The object of the present invention is to improve the wettability of blood, minimize the eluate from the substrate, and selectively capture only leukocytes, and particularly improve the passage of platelets. Another object of the present invention is to provide a white blood cell capturing device and a white blood cell capturing device. Conventionally, a high leukocyte capture rate has been achieved to some extent by a physical method of increasing the surface area of a capture material, but it is known that platelets, which are more adhesive blood cells, adhere to this. There is. Therefore, a leukocyte trap that is densely packed with this trapping material at a high density has a high leukocyte trapping rate, but at the same time cannot prevent platelet adhesion. On the other hand, in order to suppress the adhesion of platelets and capture only white blood cells at a high rate, it was necessary to chemically modify the capturing material. However, as described above, only by graft-polymerizing or coating a hydrophilic monomer or polymer, the permeability of platelets can be improved to some extent, but the leukocyte capture rate tends to be low. When the packing density of the trapping material was increased to increase the leukocyte trapping rate and the thickness was increased, the container size became larger, and the platelet permeability was reduced accordingly, which became a vicious circle. Therefore, a need has arisen for a leukocyte trap that maintains a high leukocyte capture rate and at the same time has a high platelet passage property.

[0007]

Means for Solving the Problems As a result of intensive studies by the present inventors, they have found that the leukocyte-capturing performance and platelet-passing performance can be exhibited by specifying the chemical properties of the surface of the capturing material. Moreover, in addition to this, it was found that a more excellent leukocyte trap and leukocyte trap can be obtained by specifying the physical structure such as pore size and surface area, and the present invention has been completed. That is, the object is achieved by a leukocyte trap packing density capture material is filled into 0.05 g / cm ³ or more 0.5 g / cm ³ or less of cationic groups and repeating units having a polyethylene glycol chain of from 2 to 15 It was found that this was done and the present invention was reached. Preferably, a part or all of the hydrophobic base material is made hydrophilic with a cationic group and a hydroxyl group and a polyethylene glycol chain having a repeating unit of 2 to 15 to achieve good platelet permeability.

Capturing Material The capturing material in the present invention has a structure in which the substrate is maintained in shape and has an appropriate mechanical strength, and a hydrophilic surface structural material existing on the surface by being bonded to the substrate. Refers to what is doing. Further, the capturing material as referred to in the present invention is in contact with blood and fractionated by size, adhesion, adhesion, or electrostatic, hydrophobic or other chemical, physical, or adsorption by biological interaction, Etc., or by a plurality of these actions, it means a material for separating a part or all of blood components, impurities, contaminants and the like. The effect of the present invention is particularly large and most suitable when used for capturing white blood cells. Specific examples of the shape of the capturing material include woven cloth, non-woven cloth, filter cloth type such as cotton cloth, sponge,
Examples thereof include porous bodies such as porous membranes. Preferable examples include non-woven fabrics and porous bodies because they have a good surface area, but are not limited thereto.

Material of Substrate Examples of the material of the substrate of the present invention include polyesters such as polyethylene terephthalate, polybutylene terephthalate and polyoxyethylene terephthalate, polyacrylonitrile, polyamides such as nylon 6, nylon 6,6, and the like. Aromatic polyamide, polystyrene and its derivatives, polyolefins such as polyethylene, polypropylene and polybutene, polymer compounds obtained by polymerizing methacrylic acid ester derivatives such as methyl methacrylate and ethyl methacrylate, acrylic acid ester derivatives such as methyl acrylate and ethyl acrylate Polymer compounds obtained by polymerizing poly (trifluorochloroethylene), polyvinyl formal, polysulfone, polyurethane, polyvinyl acetal, polycarbonate, etc. Synthetic polymer compounds, including homopolymers, copolymers, block polymers of the monomers of the above polymer compounds and blends and alloys of the above polymer compounds, cellulose and / or derivatives thereof, etc. And the synthetic polymer compounds shown above, and those including alloyed ones. Of the above, the hydrophobic substrate is preferably used because it has low compatibility with the polyethylene glycol chain. The term “hydrophobic” as used herein means that the contact angle with water is 85 ° or more. Examples of specific materials of the hydrophobic substrate include polyethylene, polypropylene, polyolefins such as polybutene, polyvinyl chloride, polyvinyl halides such as polytetrafluoroethylene and polytrifluoroethylene, polystyrene, polymethylstyrene, Synthetic polymer compounds such as polystyrenes such as styrene-butadiene copolymer, polycarbonate, etc., and blends and alloys of homopolymers, copolymers, block copolymers of the above polymer compounds and the above polymer compounds. However, the present invention is not limited to this as long as the contact angle with water is 85 ° or more. Preferably, the moldability of the nonwoven fabric, the fiber diameter of the resulting nonwoven fabric, the pore state formed by the fibers, from the viewpoint that this greatly affects the trapping state of white blood cells, polyethylene, polyolefin such as polypropylene, or polystyrene. Polystyrene such as styrene-butadiene copolymer is preferable. More preferred are polyolefins such as polyethylene and polypropylene because they are less likely to dissolve and are less soluble in liquids such as blood and plasma.

Hydrophilic surface structural material A hydrophilic surface structural material is an amorphous amorphous structural material, which is a structural material that is stably present on the surface by binding to a base material. From the viewpoint of improving the passage of platelets, it is preferable that the repeating unit contains a polyethylene glycol chain of 2 to 15. When ethylene glycol is repeated one time, the slow layer on the surface is short and is easily affected by the base material, so that the platelet permeability is not significantly improved, which is not preferable. When the number of repeating units is 16 or more, it is sufficient in terms of a slow layer on the surface, but it is not preferable because it is difficult to fix to the substrate and the leukocyte-capturing ability is further reduced. Therefore, from the viewpoint of easy fixing to the substrate, the best hydrophilic surface structure material can be obtained when the repeating unit has 2 to 15 polyethylene glycol chains. Further, this hydrophilic surface structure material preferably has a hydroxyl group from the viewpoint that adsorption of proteins in blood can be reduced. Furthermore, when a hydrophobic base material is used, it is preferable that a hydroxyl group is present together with the polyethylene glycol chain because the difference in hydrophilicity with the base material greatly affects platelet permeability. In addition, it is preferable to have a cationic group because an electrostatic action can be obtained because it can selectively capture only leukocytes.

The hydrophilicity of the hydrophilic surface structure material is
When measuring in the state of capture material, the contact angle to water is 8
It means a state of less than 5 °. The functional group that imparts hydrophilicity corresponds to a polyethylene glycol chain having a repeating unit of 2 to 15 and a hydroxyl group. However, the polyethylene glycol chain and the hydroxyl group may be bonded or may be present separately. Examples of the monomer having a polyethylene glycol chain that imparts hydrophilicity include methoxydiethylene glycol methacrylate, methoxytriethylene glycol methacrylate, methoxytetraethylene glycol methacrylate, methoxypentaethylene glycol methacrylate, methoxyhexaethylene glycol methacrylate, methoxyheptaethylene glycol methacrylate. , Methoxyoctaethylene glycol methacrylate, methoxynonaethylene glycol methacrylate, methoxydecaethylene glycol methacrylate,
Methoxyundeca ethylene glycol methacrylate,
Methoxy dodeca ethylene glycol methacrylate, methoxy trideca ethylene glycol methacrylate, methoxy tetradeca ethylene glycol methacrylate,
Terminal methoxy methacrylate such as methoxypentadecaethylene glycol methacrylate, methoxydiethylene glycol acrylate, methoxytriethylene glycol acrylate, methoxytetraethylene glycol acrylate, methoxypentaethylene glycol acrylate, methoxyhexaethylene glycol acrylate, methoxyheptaethylene glycol acrylate, methoxyoctaethylene Glycol acrylate, methoxynonaethylene glycol acrylate, methoxydecaethylene glycol acrylate, methoxyundecaethylene glycol acrylate, methoxydodecaethylene glycol acrylate, methoxytridecaethylene glycol acrylate, methoxytetradecaethylene glycol A terminal methoxyacrylate such as acrylate or methoxypentadecaethylene glycol acrylate, and a methacrylate or acrylate having a terminal hydroxyl group in which hydrogen is bonded instead of a methyl group, and a repeating unit having one or more polymerizable functional groups at the end is 2 Refers to all monomers having polyethylene glycol chains of -15. Further, when directly bound to a carrier, a polyethylene glycol derivative having repeating units 2 to 15 is also included. Examples of the monomer having a hydroxyl group that imparts hydrophilicity include 2-hydroxyethyl methacrylate, 1-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, 1-hydroxyethyl acrylate,
1,2-dihydroxyethyl methacrylate, 2,2-
Examples thereof include, but are not limited to, dihydroxyethyl methacrylate, vinyl alcohol, vinyl acetate and the like. Further, one or more polymerizable functional groups may be present.

Polymerizable functional group The polymerizable functional group refers to a functional group which can be polymerized alone or by two or more functional groups, and examples thereof include a carbon multiple bond such as vinyl group, acetylene group and diene group. , Epoxy group,
Examples thereof include ring structures such as an oxetane group, but are not limited thereto.

Definition of Cationic Group The term "cationic group" as used in the present invention includes amines and amine derivatives, and includes tertiary and quaternary amino groups.
Either may be used. Preferable examples include those having a pKb of 4.0 or more. Furthermore, since heparin is usually used as an anticoagulant in blood or plasma, it is more desirable that the adsorbent has less heparin adsorption. From this point, a more preferable example is represented by the following equation (a).

[0014]

[Chemical 1]

There is no particular limitation on the substituents R1, R2 and R3, and any substituent can be provided, but some substituent (for example, R1) is connected to the hydrophobic portion by a covalent bond. It is a thing. For example, it may be a hydrocarbon substituent such as hydrogen, a methyl group, an ethyl group, a propyl group, a phenyl group or a benzyl group, or a substituent containing a heteronuclear atom such as methylol or ethylol. Further, it may have a structure in which R1 and R2 (or R3) form a main chain. R2 and R3 may be cyclic with two or more, and examples thereof include pyridine, imidazole, piperidine, pyrrole, and pyrimidine.

An example of the cationic functional group is a monomer name. Allylamine, diallylamine, N, N-dimethylallylamine, N, N-diallylpiperazine, N, N-
Diallylaniline, N, N-diallylmelamine, aminostyrene, N, N-dimethylaminostyrene, N, N-
Diethylaminostyrene, vinylbenzylamine, vinylphenethylamine, N, N-dimethylvinylphenethylamine, N, N-diethylvinylphenethylamine,
N-propylvinylphenethylamine, vinylpyridine, 2-methyl-5-vinylpyridine, 2-ethyl-5
-Vinyl pyridine, 2-vinyl quinoline, 2-vinyl imidazole, 4-vinyl imidazole, vinyl pyrazoline, vinyl pyrazine, 4-vinyl pyrimidine, vinyl amine, vinyl carbazole, ethyleneimine, N-phenylethyleneimine, N, N-diethyl-N. Examples thereof include monomers such as vinylphenethylamine, diethylaminoethyl methacrylate, dimethylaminoethyl methacrylate and diethylaminoethyl styrene, and oligomers and polymers having any of these as a polymerized unit. Further, an ammonium group obtained by quaternizing these may be used. Of these, R2 and R3 are particularly preferably hydrogen (H) or an alkyl chain having 1 to 12 carbon atoms. Further, R2 and R3 are hydrogen (H) or have 1 or more carbon atoms 6
The following alkyl chains are more preferable. Specific examples thereof include diethylaminoethylstyrene, N, N-diethyl-N-vinylphenethylamine, diethylaminoethyl methacrylate, dimethylaminoethyl methacrylate, diethylaminoethyl acrylate, and dimethylaminoethyl acrylate.

Coexisting Functional Group Furthermore, a nonionic functional group may coexist with the above functional group, and examples thereof include dimethylamide, which is a nonionic functional group for the purpose of improving hydrophilicity. Groups, amide groups such as diethylamide group and diisopropylamide group, polyester chains such as aromatic polyester chains such as polyethylene terephthalate chain and polybutylene terephthalate chain and aliphatic polyester chains, polyether chains such as methylene glycol chain and propylene glycol, polycarbonate And nonionic hydrophilic functional groups such as chains, or nonionic functional groups such as alkyl chains, fluorinated alkyl chains, and allyl chains for the purpose of imparting hydrophobicity. Although any of the above functional groups may coexist, it is preferable to have a nonionic hydrophilic functional group as a good capturing material.

As a method for fixing the hydrophilic surface structure material to the substrate, any known method such as covalent bond, ionic bond, grafting method by radiation or plasma, physical adsorption, embedding or precipitation insolubilization on the surface of the substrate is used. You can also Therefore, surface modification (Japanese Unexamined Patent Publication No. 1-249063, Japanese Unexamined Patent Publication No. 502094) is carried out by a known method such as graft polymerization of a high molecular compound or its monomer using radiation or plasma, or covalent bonding. The method is preferably used in the present invention. Among the above methods for fixing the hydrophilic surface structure material,
Radiation grafting is preferred because of its stability in fixation. When the graft ratio obtained from the weight change of the base material by radiation grafting is 30% or more and 200% or less, good platelet permeability is exhibited. When the graft ratio is less than 30%, the amount introduced into the surface is insufficient, the base material is exposed, and it cannot be said that the platelet permeability is sufficient. When the graft ratio is 200% or more, sufficient platelet permeability is exhibited, but the leukocyte capture ratio is lowered, which is not preferable. More preferably, when the graft ratio is 35% or more and 170% or less, a good capturing material is obtained. At this time, when the ratio of the cationic groups is 0.05 to 10% by weight of the total graft chains, a good electrostatic effect can be obtained. When introducing a hydroxyl group, 20
Particularly good platelet permeability is obtained when the amount is ˜50% by weight. The preferred solvent for grafting is not particularly limited, but a solvent that can be immersed in the substrate is a particularly good solvent. Preferable examples include alcohols such as ethanol, methanol, propanol and butanol, and aqueous solutions thereof, hydrocarbons such as hexane and heptane, halogenated alkyls such as chloroform, methylene chloride and dichloroethane, ketones such as acetone, ethyl acetate and butyl acetate. Examples thereof include a solution in which esters such as the above and water and the like are used alone or in a mixture. The graft chain refers to a branched chain branched from the main chain, and is a chain in which a monomer is radiation-grafted or a polymer or a monomer is covalently bonded by another method.

The properties of the trapping material will be described below. The definition of the contact angle of the trapping material, the optimum range of the contact angle The liquid is brought into contact with the surface of the trapping material, and the angle between the liquid and the surface of the trapping material is defined as the contact angle θ. Then, the hydrophilicity of the surface of the capturing material can be represented by the contact angle. As a measuring method, when water droplets are dropped on the surface of the capturing material using water at 25 ° C., the angle formed between the tangent line at the contact point between the droplet and the surrounding gas and the capturing material and the plane of the capturing material is measured, The contact angle is θ. When water is immersed in the capturing material, the contact angle is 0 °. When the θ is 85 ° or more, the hydrophobic substrate exhibits sufficient hydrophobicity. When the surface is made hydrophilic and the difference in contact angle between the base material and the capturing material after surface modification is 85 ° or more, the hydrophilic group has a low affinity for the base material and is exposed to the blood side more, Platelet adhesion is suppressed. On the other hand, when the difference is less than 85 °, sufficient layer separation does not occur, the hydrophilic portion and the hydrophobic portion are mixed, and the adhesion of platelets occurs. There is no particular upper limit to the contact angle of the hydrophobic substrate, but the contact angle is 120 ° because of the ease of surface modification.
The following are preferred. More preferably, the contact angle of the hydrophobic substrate is 85 ° or more and 115 ° or less. In the base material after being hydrophilized, the higher the hydrophilicity, the more the adhesion of other plasma proteins and platelets can be suppressed.
Good platelet passage is exhibited when the angle is between 70 ° and 70 °. The adhesion of platelets can be suppressed more preferably at 0 ° or more and 60 ° or less, and most preferably at 0 ° or more and 55 ° or less.

Definition of Average Pore Diameter and Total Surface Area of Capture Material The average pore diameter in the present invention means the diameter of each of the pores dispersed in the entire cross section when the capture material is cut in the direction perpendicular to the blood flow direction. When the relationship between the diameter and the number of pores is measured and investigated, it represents the diameter converted into the circle of the most numerous pores. That is, the pores dispersed on any cut surface of the trapping material have various shapes and have various diameters, but each pore is converted into a circle having the same area as the cross-sectional area of the pore, and its diameter is Is plotted on the abscissa and the number of pores is plotted on the ordinate, and a graph is generally drawn to approximate a normal distribution. The diameter corresponding to the peak of the curve is the average pore diameter in the present invention. That is, the average pore diameter is the average diameter of the pores dispersed on each cut surface, and the average pore diameter on any cut surface must be within the range of 1 to 30 μm. Further, the blood upstream side and the downstream side refer to a portion of 0.5 mm or less from the surface of the capturing material in the thickness direction of the capturing material, and the average pore size of the capturing material on the upstream side and downstream side of the blood is measured by a scanning electron microscope. The surface of the capturing material is photographed by, and the diameter of the fine pores dispersed on the photographed surface is randomly measured by 1000 or more to obtain. Further, when it is difficult to measure the diameter of the pores when obtaining the average pore diameter of the capturing material, it is 0.
A sample with a certain thickness cut as perpendicular as possible to the blood flow direction at a portion of 5 mm or less is measured by the mercury porosimetry (Shimadzu Corporation, Poisizer 9320), and the vertical axis indicates the number of pores, and the horizontal axis indicates Take a graph of the pore size and draw the point corresponding to the peak as the average pore size. Further, the surface area in the present invention is a value obtained by multiplying the specific surface area (m ² / g) measured by the mercury penetration method by the bulk density (g / cm ³ or g / ml) of the trapping material, and the actual trapping material device. It is measured in a state similar to or close to that when the inside is filled with a porous body. In addition, the measurement by the mercury intrusion method is a value measured in a pressure range of 1 to 2650 psia.

Average Pore Size of Capture Material The present invention will be described in detail below based on embodiments. The average pore size on the downstream side of blood is 1 to 30 μm, more preferably 2 to
The thickness is preferably 25 μm, most preferably 3 to 20 μm. That is, if the average pore size is less than 1 μm, the pores are too narrow, resulting in an increase in pressure loss, and if the average pore size is greater than 30 μm, the leukocyte trapping ability decreases.

Surface Area of Capture Material The total surface area of the capture material on the downstream side of the blood of the present invention is 0.35.
˜5.70 m ² / ml, more preferably 0.50-5.
70 m ² / ml, most preferably 0.70 to 5.70 m
² / ml, and the surface area of the pores of 1 to 10 μm is preferably 50% or more, more preferably 55% or more, and most preferably 60% or more of the total surface area of the capturing material on the blood downstream side. , The surface area of the pores of 1 to 30 μm is preferably 60% or more, more preferably 65% or more, and most preferably 70% or more of the total surface area of the capturing material on the blood downstream side. Has a surface area of 38
% Or less, more preferably 30% or less, most preferably 2
It is preferably 8% or less. 4. If the total surface area of the capturing material on the downstream side of blood is less than 0.35 m ² / ml, the surface area to which leukocytes adhere will be small, resulting in leukocyte leakage.
If it exceeds 70 m ² / ml, the time required for blood treatment becomes long, and not only white blood cells but also red blood cells and platelets are likely to be trapped, resulting in increased pressure loss due to clogging, which is not suitable. Further, if the surface area of the pores of 1 to 10 μm and 1 to 30 μm of the capturing material on the blood downstream side is less than 50% and 60% of the total surface area of the capturing material on the blood downstream side, respectively, lymphocyte leakage or eye leakage will occur. Not suitable because it induces clogging. Further, since pores of less than 1 μm are pores through which blood cells do not easily pass, if the surface area of pores of less than 1 μm exceeds 38%, the recovery amount of red blood cells and platelets will be reduced, which is not suitable.

Total pore volume of trapping material The pore volume in the present invention refers to the ratio of the volume of pores per volume of the trapping material, and, like the above average pores, the thickness of the trapping material from the surface of the trapping material. A specimen with a certain thickness cut as perpendicular as possible to the blood flow direction at a portion of 0.5 mm or less with respect to the direction is measured by the mercury porosimetry (Shimadzu Corporation, Poisizer 9320), and the number of pores is plotted on the vertical axis. It is a value obtained from the number of pores and the pore diameter by drawing a graph with the pore diameter on the horizontal axis. The total pore volume of the trapping material of the present invention has an upper limit of 0.95 m in order to have some mechanical strength.
It is preferably 1 / ml or less. Further, from the viewpoint of leukocyte-capturing performance, there are many pores having a preferable pore size, and it is effective that the contact area is larger. Therefore, the lower limit is 0.4 ml / ml. ml or more is good, preferably 0.45 ml / ml or more, more preferably 0.50 ml
/ Ml or more.

Partial Pore Diameter of Capture Material When a study was conducted to develop a high-performance capture material, the average pore diameter and the total pore volume in the above-specified ranges and the pore diameter of 1 were obtained.
The volume of the pore portion having a pore size of ˜30 μm needs to be 75% or more of the total pore volume, and preferably, the volume of the pore portion having a pore diameter of 1 to 30 μm has a volume of 85% or more of the total pore volume. In order to reduce clogging and to have a high leukocyte-capturing ability with a leukocyte residual rate of 10 ⁻⁴ or less, the average pore diameter and the total pore volume in the above-mentioned specific ranges and the volume of the pore portion having a pore diameter of 1 to 30 μm are obtained. It has been found that a value of 70% or more of the total pore volume leads to good results.

Specific surface area of capturing material The specific surface area is determined by taking mechanical strength and leukocyte capturing performance into consideration.
Good when it is 0.5 to 15 m ² / g, preferably 1 to
15 m ² / g, when more preferably the 2 to 15 m ² / g,
Sufficient leukocyte capture performance.

Average fiber diameter of capture material, coefficient of variation of fiber diameter When a fibrous capture material such as a non-woven fabric is used, since the fiber diameter contributes to the pore diameter and the pore distribution, it is also important to show the effective average fiber diameter. Is. In the measurement of the average fiber diameter of the present invention, the surface of the fibrous trapping material is photographed by a scanning electron microscope, and the diameter of the yarn dispersed on the photographed surface is randomly determined to be 1
It is determined by measuring 00 or more pieces. The fiber diameter of the capturing material effective in mechanical strength and leukocyte capturing performance is 0.3 μm or more and 10 μm or less, and the leukocyte capturing performance is improved as the thread diameter is smaller. Therefore, 0.3 μm or more and 5 μm or less is more preferable. Is 0.3 μm or more and 3 μ or less. Furthermore, the distribution of the fluctuation of the fiber diameter from the average fiber diameter is preferably narrow, and the vertical fluctuation needs to be within 20 to 60%. The vertical variation is preferably within 20 to 50%, more preferably within 20 to 45% to provide a uniform capturing material.

Substrate Production Method Further, the substrate used as the capturing material of the present invention may be produced by a known method. Specifically, as the production of the porous body, a normal pressure foaming method or a pressure foaming method is used. , Foaming decomposition method such as extrusion foaming method, injection foaming method, solvent vaporization method, gas mixing method, chemical reaction method, elution method, sintering method, etc., secondary such as hot press compression, swelling with an appropriate liquid, etc. Those processed and controlled to have the pore size distribution defined in the present invention are preferable. or,
Examples of the method for producing the fibrous medium include methods such as melt blow method and flash spinning. Further, the produced fiber is subjected to secondary processing such as press compression, heat shrinkage, treatment with an appropriate liquid, and the pore diameter defined in the present invention. Those controlled to have a distribution are preferable.

Leukocyte capturing device The present invention relates to a leukocyte capturing device in which a container is filled with the above-mentioned capturing material. Container shape of leukocyte capture device The container shape is not particularly limited as long as it is a container having an inlet and an outlet for blood, but, for example, a container that can be filled with a capture material in a laminated form, a cylindrical shape, a triangular shape A columnar container such as a columnar, square columnar, hexagonal columnar, octagonal columnar, etc., further, a container in which a capturing material can be wound in a cylindrical shape and filled, or a blood flow enters from the outer periphery of the cylinder to the inner side, And a container characterized in that they collect at the outlet of the blood and have a good shape. Further, a container or the like having a shape such that its cross-sectional area such as a cone shape becomes smaller as it goes from the inlet to the outlet is used. At this time, the ratio of the cross-sectional area of the container to the length (cross-sectional area / length, S / D) of 10 cm or more and 500 cm or less is a good S / D. When processing a large amount of blood for extracorporeal circulation or for rapid rapid blood transfusion, in order to keep the pressure loss small, the thickness cannot be increased, and it is inevitably a large cross-sectional area. In order to make it a white blood cell trap, the capturing material is wrapped in a cylindrical shape and its both end surfaces are sealed, and the blood inlet of the container is on the outer surface of the cylindrical capturing material and the inner surface of the cylindrical capturing material. It is particularly preferable to use a shape in which the blood outlets of the containers communicate with each other, and the blood inlet and outlet are separated by a trapping material that is cylindrically wound.

Packing Density of Leukocyte Capture Device The packing density means the weight per certain volume when the container is filled with the capturing material, and the packing density of the container is 0.
It is desirable to fill it with 05 or more and 0.5 g / cm ³ or less to form a leukocyte trap. Further, in order to prevent clogging, increase in pressure loss, and smooth flow, the preferable packing density is 0.1 or more and 0.4 g / cm ³ or less, and the more preferable packing density is 0.1 or more and 0.3 g or less. / Cm ³ or less.

The cross-sectional area and thickness of the leukocyte-capturing device The cross-sectional area of the leukocyte-capturing device may be any size, but it is 0.5 c because of its ease of manufacture and blood throughput.
The size is preferably m ² or more and 300 cm ² or less, more preferably 250 cm ² or less, and further preferably 200 cm ² or less from the viewpoint of miniaturization and operability. In the case of a structure wound in a cylindrical shape, the area of the outermost circumference is the cross-sectional area. Although the total thickness of the capturing material depends on its shape, the thickness of the entire capturing material is preferably 0.1 mm or more and 50 mm or less as a practical range. Considering the priming property, the thickness is preferably 0.1 mm or more and 45 mm or less, and more preferably 0.1 mm or more and 40 mm or less.

Cascade of Leukocyte Capture Device The leukocyte capture device of the present invention is a leukocyte capture device in which a container having an average pore size of 1 to 30 μm is partially or wholly filled in a container having an inlet and an outlet for blood. Then, the average pore size of the capturing material decreases substantially continuously or stepwise from the blood inlet to the outlet, and the total surface area of the blood capturing downstream is 0.35 to 5.70 m ² / ml. Yes, one of these
The white blood cell selective trap can be characterized in that the surface areas of the pore portions of 10 μm and 1 to 30 μm are 50% or more and 60% or more, respectively. The continuous or stepwise reduction of the average pore diameter in the present invention means that when one capture material is cut in the blood flow direction, the pore diameter of the capture material gradually decreases from the upstream side to the downstream side of blood. This is called a continuous reduction, and a case where several trapping materials having a substantially uniform average pore diameter are stacked in the order of the average pore diameter and filled in a container is called a stepwise reduction. Therefore, in the leukocyte trap of the present invention, a leukocyte trap in which the average pore diameter of the trapping material near the inlet is 5 to 30 μm and the average pore diameter of the trapping material near the outlet is 2 to 25 μm is also preferably used. To be When it is 3 μm or less on the inlet side, clogging by blood is seen, which is not preferable, and when it is 30 μm or more, leukocytes are leaked due to large pores. For higher performance, the average pore diameter on the inlet side is preferably 8 to 25 μm, and the average pore diameter of the capturing material near the outlet is preferably 3 to 20 μm. Particularly when the capturing material is a fiber such as a non-woven fabric, the average fiber diameter thereof is 1.5 μm to 3.5 μm on the inlet side and 0.3 μm to about the outlet.
A leukocyte trap can be made by using a trapping material of 2.5 μm, and more preferably, the average fiber diameter thereof is 1.5 μm to 2.5 μm at the inlet side and 0.5 μm to near the outlet.
A white blood cell trap having a thickness of 2.0 μm and a pre-capture material having an average fiber diameter of 1 mm to 5 μm on the most inlet side is preferably used as the pre-capture material.

Pre-Capturing Material for Leukocyte Capture Device The leukocyte capture device of the present invention, when handling blood products,
To prevent clogging due to micro-aggregates, etc., the average pore diameter of the pre-capture material is 100-400μ.
m pre-capture material can be used. The structure of the pre-capturing material may be any form similar to that of the capturing material such as a fiber or a porous body, and the average pore diameter is 100 to 4
It is preferable that the average fiber diameter is 00 μm or 5 μm to 1 mm.

Sterilization Method for Leukocyte Capture Device Any known method may be used. However, for example, autoclave heat sterilization, ethylene oxide gas (EOG) sterilization, γ-ray sterilization, Radiation sterilization such as electron beam sterilization and UV irradiation can be performed.

Anticoagulant at the time of leukocyte capture The capture material of the present invention is not particularly limited as to the anticoagulant which can be used, but examples thereof include ACD-A, CPD, ethylenediaminetetraacetate (EDTA), heparin and mesylic acid. Nafamostat etc. are mentioned.

Shape of Use of Leukocyte Capture Device Before and / or after the leukocyte capture device of the present invention, a blood reservoir such as a blood outlet, a blood collection port, a blood bag, a blood circuit, a chamber, a drip chamber, a drip chamber with a mesh, and the like, For extracorporeal circulation with any or more of clamps, clamps such as roller clamps, needles, blood pump tubes, anticoagulant introduction parts such as heparin tubes, column pressure measurement tubes, pressure measurement parts such as pressure gauges, etc. A circuit or a circuit for blood transfusion can be used. Furthermore, as a means for feeding blood, a pump such as a blood pump, a liquid feeding pump, a suction pump and a peristaltic pump can be incorporated and used in the middle of the circuit. Further, it is possible to favorably use even a drop due to the own weight of blood. As the drug solution and other solutions, known ACD-A, ACD-B, ACD-C, CPD, heparin, anticoagulant such as nafamostat mesylate, cell preservation solution such as erythrocyte preservation solution, glucose solution, lactated Ringer's,
Examples thereof include, but are not limited to, blood component adjusting solutions such as various electrolyte solutions such as physiological saline. Preferably, a leukocyte capturing device including at least a blood inlet / outlet, a blood pump, and a blood reservoir, and including a leukocyte capturing device is favorably used in terms of workability at the time of capturing air into the column and capturing during leukocyte capturing. . During the extracorporeal circulation, it is particularly preferable to have at least a pressure measuring means such as a blood pump or a pressure gauge in order to process a large amount of blood or capture leukocytes at a fixed flow rate.

Use of leukocyte trap and leukocyte trap The leukocyte trap and leukocyte trap of the present invention are used as a trapping material for blood transfusion and blood of an autoimmune disease such as systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. Used for extracorporeal circulation such as leukocyte capture, leukemia, leukocyte capture from blood of cancer patients, leukocyte capture for the purpose of pre-transplant immune function deterioration, and capture of leukocytes from postoperative perfused blood in cardiac surgery, It is preferably used for removing dust such as bone debris during post-operative blood recovery and for preventing inflow of adsorbent debris into the body by extracorporeal circulation.

Leukocyte removal method The present invention also discloses a leukocyte capture method using the above-mentioned capture material, leukocyte capture device and leukocyte capture device. Leukocyte capture conditions The present invention is a capture method in which blood is flown at a flow rate of 1 to 100 ml / min using the above-described capture device and leukocyte capture device, and the linear velocity at this time is 0.05 to 15 cm / min. From a practical point of view, the slower the flow rate, the higher the leukocyte-capturing ability, but the processing time becomes longer. Therefore, the flow rate is more preferably 1 to 80 ml.
When the linear velocity is 0.1 to 10 ml / min, the leukocyte-capturing ability is high. In addition, as a method for passing blood, it may be continuously passed or intermittently passed depending on the necessity of use or the equipment condition of equipment.
At this time, when the blood stays in the leukocyte trap for a long time, the leukocyte trapping ability is enhanced, but at the same time, useful plasma protein adsorption is observed. Therefore, the present invention is preferably used when the residence time of blood in the leukocyte trap is 10 seconds or more. The time is more preferably 1 minute or more, and further preferably 10 minutes or more. Further, if blood stays in the white blood cell trap for a long time, there is a risk of causing nonspecific adsorption of blood components and blood coagulation.
It is preferably not more than minutes.

Temperature Conditions Adhesion of blood cells is greatly affected by the temperature of blood at the time of capturing leukocytes. When the temperature becomes high, the blood becomes denatured, or the leukocyte has a high deforming power and a low capturing power. On the other hand, if the temperature is too low, the viscosity increases, the flow becomes smooth and disappears, and the pressure loss increases. Therefore, it is preferable that leukocytes are easily captured when the temperature is low, preferably 4 ° C or higher and 40 ° C or lower, and more preferably 37 ° C or lower, most preferably 25 ° C or lower, and good leukocyte capture can be performed. As a temperature control method, the white blood cell trap may be cooled, or it may be cooled before introducing blood into the white blood cell trap, and in any case, it is preferable that the temperature is controlled during the white blood cell trap.

Leukocyte Capture Method In the leukocyte capture method of the present invention, leukocytes are captured from blood products, fresh whole blood, fresh PC, preserved blood and the like using the leukocyte trap or the leukocyte trap. Examples of blood products include citric acid anticoagulants (ACD-A, CP
D) added erythrocyte concentrate (CRC), or platelet concentrate (PC) and MAP or SAGM as erythrocyte preservation solution
Alternatively, a CRC added with ADSOL or the like can be used.

[0040]

EXAMPLES Next, the present invention will be described in detail with reference to specific examples.

EXAMPLE 1 By radiation grafting, 15% by weight of methoxytriethylene glycol methacrylate and 0.
A polypropylene non-woven fabric (fiber diameter 1.7 μm, basis weight 60 g / m ² , thickness 0.23 mm, contact angle 92 °) was immersed in an ethanol solution containing 5% by weight of N, N-dimethylaminoethyl methacrylate. Then, nitrogen bubbling was performed to replace the dissolved oxygen in the polymerization solvent. To this
The wire was irradiated with 25 kGy for graft polymerization. After the polymerization, the polymer was washed with a sufficient amount of ethanol solution to remove excess oligomer. After the vacuum drying, the contact angle of the capturing material with water was measured, and it was set to 0 ° because the water was immediately immersed. At this time, the difference in contact angle before and after hydrophilization was 92 °. The graft ratio calculated from the weight change before and after grafting was 93%. Average pore size is 12.3 μm, total pore volume is 0.86 ml / ml, total pore area is 0.88 m
² / ml, the pore volume with a pore size of 1 to 30 μm is 96
%Met. A container having an inlet and an outlet (thickness 1 cm, cross-sectional area 1.5 × 1.5 cm) was filled with this capturing material, and the thickness of the capturing material was 3.0 mm. The packing density at this time is 0.2
It was 6 g / cm ³ . Using this column, a white blood cell capture test was carried out with fresh bovine blood (anticoagulant ACD-A). When the time when the filling liquid in the column was replaced with blood was the start time, the white blood cells at the start time Capture rate is 99.99%
The platelet passage rate at this time was 58%. The eluate test was conducted in accordance with the adsorption blood purifier quality standard, using sample 1.5.
g was eluted with 150 ml of water for injection at 121 ° C. for 20 minutes by a high-pressure steam sterilizer, and the obtained eluate was analyzed. As for items, the ultraviolet absorption spectrum and the evaporation residue were attached. The ultraviolet absorption spectrum of the scavenger was as low as 0.025 and the evaporation residue was 0.2 mg.

[0041]

Example 2 By the radiation grafting method, 15% by weight of methoxytriethylene glycol methacrylate, 10% by weight of 2-hydroxyethyl methacrylate and 0.5
A polypropylene non-woven fabric (fiber diameter 1.7 μm, basis weight 60 g / m ² , thickness 0.23 mm, contact angle 92 °) was dipped in an ethanol solution containing wt% N, N-dimethylaminoethyl methacrylate. Nitrogen bubbling was performed to replace the dissolved oxygen in the polymerization solvent. To this
The wire was irradiated with 25 kGy for graft polymerization. After the polymerization, the polymer was washed with a sufficient amount of ethanol solution to remove excess oligomer. After the vacuum drying, the contact angle of the capturing material with water was measured, and it was set to 0 ° because the water was immediately immersed. At this time, the difference in contact angle before and after hydrophilization was 92 °. The graft ratio determined from the weight change before and after grafting was 158%. In addition, CWST82dy of capture material
ne / cm, average pore diameter 9.4 μm, total pore volume,
0.81 ml / ml, total pore area 0.91 m ² / m
1, and the volume of pores having a pore size of 1 to 30 μm was 98% of the whole. The thickness of the trapping material is 3.0 mm and the cross-sectional area is 49 x
It was filled in a container with an inlet and an outlet of 49 mm. The packing density at this time was 0.26 g / cm ³ . When a white blood cell capture test was carried out with fresh bovine blood (the anticoagulant heparin), the white blood cell capture rate at the start was 99.99% when the time when the filling liquid in the column was replaced with blood was the start time.
The platelet passage rate at this time was 61%. The eluate test was carried out in the same manner as in Example 1, and the ultraviolet absorption spectrum of the above-mentioned trapping material had an absorbance of 0.021 and an evaporation residue of 0.
It was a very low value of 2 mg.

[0042]

Example 3 12.5% by weight by the radiation grafting method
Methoxytriethylene glycol methacrylate, 7
A polypropylene non-woven fabric (fiber diameter: 1.7 μm, basis weight: 60 g / m ² , thickness: 0.1%) was added to an ethanol solution containing 0.5% by weight of hydroxyethyl methacrylate and 0.5% by weight of N, N-dimethylaminoethyl methacrylate.
23 mm, contact angle 95 °) was immersed and nitrogen bubbling was performed to replace the dissolved oxygen in the polymerization solvent. This was irradiated with γ-rays at 25 kGy for graft polymerization. After the polymerization, the polymer was washed with a sufficient amount of ethanol solution to remove excess oligomer. After the vacuum drying, the contact angle of the capturing material with water was measured, and it was set to 0 ° because the water was immediately immersed. At this time, the difference in contact angle before and after hydrophilization was 95 °. The graft ratio obtained from the weight change before and after grafting was 127%. The trapping material had a thickness of 3.0 mm and was filled in a container having an inlet and an outlet with a cross-sectional area of 49 × 49 mm. The packing density at this time was 0.26 g / cm ³ . When a white blood cell capture test was carried out with fresh bovine blood (the anticoagulant heparin), the white blood cell capture rate at the start was 99.99% when the time when the filling liquid in the column was replaced with blood was the start time. The platelet passage rate at this time was 58%.

[0043]

COMPARATIVE EXAMPLE 1 Polyethylene terephthalate was prepared by the radiation grafting method as in Example 1 in an ethanol solution containing 15% by weight of methoxytriethylene glycol methacrylate and 0.5% by weight of N, N-dimethylaminoethyl methacrylate. Non-woven fabric (fiber diameter 1.7μ
m, basis weight 60 g / m ² , thickness 0.23 mm, contact angle 7
1 °) was immersed and nitrogen bubbling was performed to replace the dissolved oxygen in the polymerization solvent. Irradiate this with 25 kGy of γ-rays,
Graft-polymerized. After the polymerization, the polymer was washed with a sufficient amount of ethanol solution to remove excess oligomer. After vacuum drying, the contact angle of this capturing material with water was measured,
Since water was immediately immersed, the angle was set to 0 °. At this time, the difference in contact angle before and after hydrophilization was 71 °. Further, the graft ratio obtained from the change in weight before and after grafting was 95%.
The thickness of this trapping material was 3.0 m as in Example 1.
m, and filled in a container having an inlet and an outlet (thickness 1 cm, cross-sectional area 1.5 × 1.5 cm). The packing density at this time was 0.26 g / cm ³ . Fresh cow blood (anticoagulant AC
When the white blood cell capture test was performed in D-A), the time when the filling liquid in the column was replaced with blood was the start time,
The white blood cell capture rate at the start was 99.97%, and the platelet passage rate at this time was 35%. The eluate test was carried out in the same manner as in Example 1, and the ultraviolet absorption spectrum absorbance of the above capturing material was 0.080, and the evaporation residue was 0.8 mg.

[0044]

COMPARATIVE EXAMPLE 2 By the radiation grafting method as in Example 1, a non-woven fabric of polybutylene terephthalate (fiber) was added to an ethanol solution containing 15% by weight of methoxytriethylene glycol methacrylate and 5% by weight of 2-hydroxyethyl methacrylate. Diameter 1.7 μm, basis weight 6
0 g / m ² , thickness 0.23 mm, contact angle 70 °) was immersed and nitrogen bubbling was performed to replace the dissolved oxygen in the polymerization solvent. This was irradiated with γ-rays at 25 kGy for graft polymerization. After the polymerization, the polymer was washed with a sufficient amount of ethanol solution to remove excess oligomer. After the vacuum drying, the contact angle of the capturing material with water was measured, and it was set to 0 ° because the water was immediately immersed. The difference in contact angle before and after hydrophilization at this time was 70 °. Further, the graft ratio calculated from the weight change before and after the graft was 97%. This trapping material has a thickness of 1.5 mm as in the case of Example 1, and a container having an inlet and an outlet (thickness 1 cm, cross-sectional area 1.5 × 1.5 c).
m). The packing density at this time is 0.13 g / cm
^{Was 3} . This trapping material was filled in a container having an inlet and an outlet similar to those in Example 1, and fresh cow blood (anticoagulant ACD-A) was used.
When a white blood cell capture test was carried out, the white blood cell capture rate at the start was 99.31%, and the platelet passage rate at this time was , 39%. The eluate test was carried out in the same manner as in Example 1, and the ultraviolet absorption spectrum of the above capturing material was that the absorbance was 0.088 and the evaporation residue was 0.83 mg.

[0045]

[Example 4] A polypropylene non-woven fabric (a non-woven fabric made of polypropylene was added to an ethanol solution containing 7.5% by weight of methoxytriethylene glycol methacrylate and 0.5% by weight of N, N-dimethylaminoethyl methacrylate by a radiation graft method. Fiber diameter 2.5 μm, basis weight 60 g / m ² ,
A thickness of 0.24 mm and a contact angle of 92 °) was immersed, and nitrogen bubbling was performed to replace the dissolved oxygen in the polymerization solvent. This was irradiated with γ-rays at 25 kGy for graft polymerization. After the polymerization, the polymer was washed with a sufficient amount of ethanol solution to remove excess oligomer. After vacuum drying, the contact angle of this trapping material with water was measured, and as the water was immediately immersed,
It was set to 0 °. At this time, the difference in contact angle before and after hydrophilization is 92
It was °. The graft ratio calculated from the weight change before and after grafting was 93%. Average pore size is 15.3 μm,
The total pore volume is 0.88 ml / ml and the total pore area is 0.
The pore volume of 76 m ² / ml and the pore size of 1 to 30 μm was 95% of the whole. The container having an inlet and an outlet (thickness 1 cm, cross-sectional area 49 × 49 mm) was filled with this trapping material, and the trapping material had a thickness of 3.0 mm. C using this column
A leukocyte capture test was performed on RC blood (anticoagulant CPD) at a flow rate of 1 ml / min using a peristaltic pump.
When the start time was the time when the column filling liquid was replaced with blood, the white blood cell capture rate at the start was 99.999%, and the platelet passage rate at this time was 55%.

[0046]

Comparative Example 3 A non-woven fabric made of polybutylene terephthalate was placed in an ethanol solution containing 7.5% by weight of methoxytriethylene glycol methacrylate and 0.5% by weight of N, N-dimethylaminoethyl methacrylate by a radiation grafting method. (Fiber diameter 2.5 μm, basis weight 6
0 g / m ² , thickness 0.24 mm, contact angle 71 °) was immersed and nitrogen bubbling was performed to replace the dissolved oxygen in the polymerization solvent. This was irradiated with γ-rays at 25 kGy for graft polymerization. After the polymerization, the polymer was washed with a sufficient amount of ethanol solution to remove excess oligomer. After the vacuum drying, the contact angle of the capturing material with water was measured, and it was set to 0 ° because the water was immediately immersed. At this time, the difference in contact angle before and after hydrophilization was 71 °. The graft ratio determined from the change in weight before and after grafting was 88%. Average pore size is 1
The total pore volume was 7.3 μm, the total pore volume was 0.81 ml / ml, the total pore area was 0.59 m ² / ml, and the pore volume with a pore size of 1 to 30 μm was 70% of the whole. A container with an inlet and an outlet (thickness 1 cm, cross-sectional area 49 x 49 m
m) and the thickness of the capturing material was set to 3.0 mm. Using this column, a white blood cell capture test was performed on CRC blood (anticoagulant CPD) at a flow rate of 1 ml / min using a peristaltic pump, and the time when the filling liquid in the column was replaced with blood was taken as the start time. , The white blood cell capture rate at the start was 99.
98%, and the platelet passage rate at this time was 39%.

[0047]

Example 5 A nonwoven fabric manufactured by the same method as in Example 2 in which a blood pump and a drip chamber were incorporated in a blood circuit had an average fiber diameter of 1.7 μm and an average pore size of 9.4 μm.
m, the total pore volume was 0.81 ml / ml, the total pore area was 0.91 m ² / ml, and the pore volume with a pore size of 1 to 30 μm was 98% of the whole. This non-woven fabric is 15 cm x 240
Cut into a size of cm, wrap it in a cylinder, fill a cylindrical container with a diameter (inner diameter) of 5 cm x 15 cm, close both upper and lower ends with polyurethane, and make sure the blood flow from outside to inside. A leukocyte capturing device was prepared in which a blood outlet channel was formed in the central portion on the downstream side. The filling density at this time was 0.135 g / cm ^3, which was connected to a blood circuit incorporating a blood pump and a drip chamber, and 4 l of blood using ACD-A as an anticoagulant similar to that of Example 1 was put into a blood pool. The flow rate was 50 ml / min to capture leukocytes. As a result, the white blood cell capture rate was 99.99%, and the platelet passage rate at the start at this time was 61%.

[0048]

By using the white blood cell trap and the white blood cell trap of the present invention, the adhesion of platelets can be suppressed from the start and the white blood cells can be trapped efficiently. Particularly in the field of blood transfusion, it is possible to minimize the loss of platelets from concentrated platelets and to selectively capture leukocytes. In addition, in the extracorporeal circulation, the loss of platelets required in the body can be prevented and leukocytes can be captured.

Claims (2)

[Claims] 1. A cationic group and a repeating unit 2 on the surface.
.About.15 fibers having polyethylene glycol chains or polymeric porous bodies having continuous pores, having an average pore diameter of 1 to
A leukocyte trap that traps leukocytes from a liquid in which leukocytes are suspended, characterized in that a trapping material having a packing density of 0.05 μm / cm ³ or more and 0.5 g / cm ³ or less is incorporated. 2. A cationic group and repeating units 2 to 15
The capturing material in which the hydrophilic surface structure material having a hydrophilic part having a polyethylene glycol chain and a hydrocarbon-based hydrophobic part is bonded to a hydrophobic base material whose main component is a hydrocarbon at the hydrophobic part is A white blood cell trap characterized by being built-in.