JP3534361B2 - Leukocyte removal material - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [0001] The present invention relates to leukocytes from leukocyte suspensions.
The present invention relates to a leukocyte removing material for removing spheres. Specifically, blood transfusion
Or leukocytes that are mixed in the blood during extracorporeal circulation
Leukocyte removal to adjust the leukocyte removal blood product
Regarding materials. [0002] In recent years, with the advancement of immunology and transfusion,
Only the components necessary for treatment of various diseases from conventional whole blood transfusions
Ingredients for transfusion are being transfused. Completion
Blood transfusion reduces the burden on patients due to blood transfusion and is effective
It is an excellent blood transfusion therapy that increases fruit and is used for component blood transfusion.
Various blood products: concentrated red blood cells (CRC),
Thick platelets (PC), platelet poor plasma (PPP), etc. are donated
Thus, the whole blood obtained is separated and adjusted by centrifugation.
However, in blood products separated by centrifugation
Contains a lot of white blood cells.
It has become clear that side effects are induced after blood transfusion
It was. Post-transfusion side effects include headache, nausea, chills, and insoluble
Immune disorders due to relatively minor side effects such as bloody fever
For patients with blood transfusions, the transfused white blood cells
Graft-versus-host reaction with lethal effects on skin and internal organs
(GVHR) induction, cytomegalovirus infection, etc.
Infection and alloantigen sensitization by viruses in white blood cells
Serious side effects such as are known. After such a blood transfusion
In order to prevent side effects, white
It is effective to remove blood cells. Headache, nausea, chills, non-hemolytic fever reaction
To prevent any relatively minor side effects,
The number of white blood cells injected into the recipient with blood is reduced to about 100 million or less.
For this purpose in blood products
The remaining rate of leukocytes of 10^-1-10^-2Remove until
There is a need to. GVHR and cytomegalovirus
To prevent serious side effects such as infection and alloantigen sensitization
Although there is still no established theory, the leukocyte residual rate is 10^-Four~
10^-6Expected to prevent by removing until below
Has been. Also, like HIV, both leukocytes and plasma
The virus present in the
It is expected that the frequency of dyeing may be reduced. As a method for removing leukocytes from blood products
Centrifuge method using the specific gravity difference of blood and non-woven fabric etc.
Sponge with various fibrous media and three-dimensional continuous mesh holes
Two types of filter methods using structural materials as filter materials
Although broadly classified, it has good leukocyte removal efficiency and simple operation.
In addition, the filter method is widely used because of the advantages of low cost.
It is often used. The removal of leukocytes by the filter method
Adhesion removal using leukocyte adhesion is the main mechanism
It is considered. In Japanese Patent Laid-Open No. 3-158168, white blood
As the thickness of the sphere removal material increases, the leukocyte removal material passes through.
Disclosed that the excess white blood cell concentration decreases exponentially.
This is because white blood cells come into contact with the surface of the white blood cell removal material
Each suggests that it will stick with a certain probability
And supports the above-mentioned debonding theory. Therefore,
High performance in conventional leukocyte removal filters
Increasing the contact frequency between the sphere and the leukocyte removal material,
For example, when using fiber as a leukocyte removal material, the average
For reducing fiber diameter and increasing packing density
The main considerations have been made. However leukocyte removal
Paying attention to the surface chemical properties of the material, against white blood cells on the material surface
High affinity for higher leukocyte removal ability
It is not enough to consider the rationalization. As an example of study focusing on the surface chemical properties of materials
WO87 / 05812 discloses an optimum amount of base for fibers.
A polymer containing an ionic functional group and a nonionic hydrophilic group
If the platelets pass through by a method such as
Both examples show that the leukocyte removal rate also increases.
And polymers with more basic functional groups
Example, the removal rate of both platelets and leukocytes increases.
Is shown in Cell surface generally has a negative charge
Considering that the polymer with basic functional groups
Therefore, the leukocyte removal rate is increased under normal physiological conditions.
Between the basic functional group with a negative charge and the negative charge on the cell surface
This is thought to be due to the ionic bond force acting on the
The result is considered. Japanese Patent Application Laid-Open No. 1-249063 describes the fiber surface.
Chemical species with acidic functional groups and chemical groups with hydroxyl groups
Using a material whose surface has been modified with a species, white blood from platelet-containing liquids
An apparatus and method for removing blood cells is disclosed. However
However, the purpose of this material is to improve platelet permeability
However, the purpose is not to increase the adhesion probability of leukocytes,
This surface chemical modification improves the adhesion probability of leukocytes.
There is no mention of that. Japanese Patent Laid-Open No. 5-148151 discloses one type on the surface.
Nonwoven fabric, woven fabric or continuous pores having the above acidic functional groups
Made of whole blood or erythrocytes by polymer porous body with
A material for removing leukocytes from an agent is disclosed. However
However, as described in the examples of this specification, this
Leukocyte residual rate by material is 10^-3.2-10^-3.7And
Leukocyte residual rate is 10^-FourAdequate leukocyte removal such as
I have not come out of my ability. Japanese Patent Laid-Open No. 4-272768 discloses a small amount of base material.
A polymer with basic functional groups on at least one surface
First introduced by Zuma air-layer grafting, then sulfonic acid
A polymer having an acidic functional group such as
Utilizing intermolecular attractive force and clonal force for polymers with functional groups
And physically bonded materials are disclosed. However,
As a result of the study by the present inventors, the surface of this material is substantially
Is a high content of acidic functional groups introduced later by physical adhesion
Because it is covered with a child,
Sufficient leukocyte removal ability due to low ionic action
I did not come out.Japanese Patent Laid-Open No. 6-247862.
The white blood cell residual rate is 10 ^-4 Enough to be
A leukocyte removal filter showing leukocyte removal ability is disclosed
However, the filter has a basic functional group and a nonionic surface.
A nonionic hydrophilic group of a basic functional group.
The molar ratio to the specific range of 0.6 to 6 and the salt
Basic functional group is 5 × 10 ^-5 ~ 0.1 meq / m ² Dense
High molecular weight porous material characterized by existing on the surface
A filter material comprising basic functional groups and acidic
Leukocyte removal of the present invention which requires both functional groups as essential requirements
It is different in material and structure. [0009] The present invention is a leukocyte removing ability.
To provide a new leukocyte removal material
The The present invention also provides for blood transfusion and extracorporeal circulation.
Prepare a leukocyte-removed blood product that removes contaminating leukocytes.
A leukocyte-removing material is provided. [0010] The object is to eliminate leukocytes.
The substrate to be removed is a porous element, and the surface portion of the substrate is
White blood cells into which basic and acidic functional groups have been introduced
Achieved by removal material. That is, basic functional groups and acidic
Leukocyte-removing materials that have both functional groups on their surface are much more expensive.
The leukocyte of the present invention
The removal material has been completed. Both basic and acidic functional groups on the surface
Why is the leukocyte removal ability much higher
It is not clear what will happen. In general
Considering that cells have a negative charge under physiological conditions
Leukocytes by introducing a basic functional group with a positive charge
This removal is said to be due to electrostatic interactions.
On the other hand, for acidic functional groups with negative charge under physiological conditions
The electrostatic repulsive force works and the adhesion is likely to be suppressed
However, cells adsorb to the surface of materials with acidic functional groups
Faster adsorption of certain proteins in plasma
However, adhesion of leukocytes is promoted by mediation of this protein
It is said that it will be done. But basic officer
Compared to materials with only functional groups or acidic functional groups on the surface
Compared to materials with both functional groups on the surface, leukocyte removal
High castration, and this high leukocyte removal ability only with the above hypothesis
Seems to be insufficient to explain. Probably in white blood cells
Includes leukocytes with high affinity for basic functional groups and acidic functional groups
There are white blood cells with high affinity, so basic functional groups
White for materials with both surface and acidic functional groups
Adhesion of blood cells to the material surface is accelerated, and white blood is
Interactions between spheres work, such as leukocyte aggregates
Will form and more white blood cells will stick to the material surface
And has a much higher leukocyte removal ability
It is thought that it was. The leukocyte-removing material of the present invention has a surface portion.
A material having both a basic functional group and an acidic functional group. salt
The distribution of basic functional groups and acidic functional groups on the material surface is
The bill of materials so that both functional groups can act on cells in the blood
There is no particular limitation as long as it exists on the surface.
May be, but preferably basic functional group and acidic functional group
Is a microphase-separated distribution that is regularly arranged on the surface.
Preferably, basic functional group and acidic functional group are random
Distributed almost uniformly on the material surface
It is preferable that In the present invention, the basic functional group is a primary amino group.
Group, secondary amino group, tertiary amino group, quaternary ammonia
Um group and bases such as pyridyl group and imidazolyl group
Functional group-containing aromatic groups, etc., and these functional groups
As long as it is on the surface of the material. In addition, the above base
Of any form of monomer or polymer having a functional functional group
Used for making the leukocyte removal material of the present invention even in a class
can do. Specific examples of chemical species as monomers
For example, allylamine, diallylamine
Allylamine derivatives such as N, N-dimethylallylamine
Conductor, dimethylaminoethyl (meth) acrylate, di
Ethylaminoethyl (meth) acrylate, dimethyla
Minopropyl (meth) acrylate, 3-dimethylamino
No-2-hydroxypropyl (meth) acrylate, etc.
(Meth) acrylic acid ester derivatives, aminostyrene,
N, N-dimethylaminomethylstyrene, N, N-die
Tylaminostyrene, N, N-dimethylaminomethyls
Styrene, N, N-diethylaminomethylstyrene, etc.
Tylene derivatives, vinyl pyridine, 2-methyl-5-vinyl
Rupyridine, 2-ethyl-5-vinylpyridine, vinyl
Quinoline, vinyl imidazole, vinyl pyrazoline, bi
Aromatic compounds such as nilpyrazine and vinylpyrimidine
Nyl derivatives and the above vinyl compounds
Derivatives etc. made into quaternary ammonium salts by rukill
Can be mentioned. However, because it is used in the present invention
The chemical species having a basic functional group that is
Limited to polymers of monomers and their monomers
It is not a thing. Further, as the acidic functional group in the present invention,
Carboxyl group, phosphoric acid group, sulfonic acid group, phenol
Group, and these functional groups are present on the material surface.
That's fine. In addition, monomers having the above acidic functional group
-Leukocytes of the present invention in any form of polymer species
It can be used to make the removal material. mono
If you give a specific example of the chemical species as
(Meth) acrylic acid, 2-methacryloyloxye
Tyrsuccinic acid, mono (2- (meth) acryloyloxy
Ethyl) acid phosphate, 2-sulfoethyl
(Meth) acrylic acid derivatives such as (meth) acrylate,
Styrene derivatives such as sodium styrenesulfonate, vinyl
Phenol derivatives such as nylphenol, allyl sulfone
Allyl compounds such as sodium acid, acetylene derivatives,
Lioxane derivatives, etc. can be mentioned. But,
Chemical species having acidic functional groups that can be used in the present invention
Consists of the monomers exemplified above and their monomers
It is not limited to polymers. In addition, the basic functional group and the acid group described above
Monomers with both functional groups, such as amino acid derivatives
Such amphoteric species and such monomers
Limers and peptides also produce the leukocyte removal material of the present invention.
Can be used for The leukocyte removing material of the present invention has a salt on its surface.
Both basic functional groups and acidic functional groups are introduced
It is. Basic functional group and acidic functional group in the present invention
Group is a basic functional group possessed by the polymer constituting the substrate itself.
And acidic functional groups, but also basic functional groups
Or base materials that do not have acidic functional groups or both functional groups
Monomers having basic functional groups and acidic functional groups, poly
Such as covalent bonds and polymer coatings.
It may be introduced using any known method. Preferably,
For covalent bonds to prevent the polymer from falling off the substrate surface
More preferably, it is introduced. Basic functional groups and
And both acidic functional groups are covalently introduced to the material surface
As a method, it has a basic functional group and an acidic functional group
Chemical species such as polymerizable monomers or polymers
Method of introducing by raft polymerization, plasma irradiation
Introducing the method by irradiating with electron beam or ultraviolet rays
To introduce, utilizing a chemical reaction with the functional group of the substrate
There are various methods such as a method. The basic functional group on the surface of the material in the present invention
The total chargeable functional group density of acidic and acidic functional groups is dependent on the surface area of the material.
10^-Four~ 5 meq / m² It is preferable that
10^-3~ 1 meq / m² It is more preferable that
And 10^-3~ 0.1 meq / m² More preferred to be
That's right. Total charged functional group density is 10^-Fourmeq / m² Less than
Depending on the type of functional group,
It is not preferable because the effect may not be obtained.
5 meq / m² Exceeding a radiation graft
Amount of chemical species introduced when the substrate surface is modified
May overfill the gaps in the material.
It is not preferable. Basic functional group on material surface in the present invention
The density is preferably 0.05 to 20 times the acidic functional group density,
Furthermore, 0.1 to 10 times is preferable, and 0.3 to 5 times is more preferable.
Good. Basic functional group density is 0.05 of acidic functional group density
Electrostatic action on leukocytes by basic functional groups
The effect is lost and the ability to remove leukocytes decreases
Therefore, it is not preferable, and if it exceeds 20 times, the basic functional group
Due to its high density, other blood such as red blood cells as well as white blood cells
Sphere components also adhere to the material surface, and as a result, white blood cells can adhere
The surface of the material to be used is reduced and the leukocyte removal ability is reduced.
This is not preferable. In the present invention, the surface portion means a cell, a material, and
500 angstroms from the interface where the material contacts
Say a range within the depth. Basic functional group density and acidity
The active group density is measured by Auger electron spectroscopy (AES).
Secondary ion mass spectrometry (SIMS), electron probe microscopic part
Analysis method (EPMA), X-ray photoelectron spectroscopy (XPS), running
Using a scanning electron microscope (SEM) and multiple total reflection infrared spectrometer
Surface analysis such as infrared spectrophotometry (ATR-IR)
It can be measured by the method. Also, the material surface
Extract using appropriate methods and load contained in the extracted material
The density of the functional group is determined by the above-mentioned known method or nuclear magnetic resonance spectrum.
Analyze using methods such as Kutor (NMR) and elemental analysis
May be. In addition, the ionically adsorbed color on the charged functional group
Simple measurement by dye adsorption method and titration method
You can also. The charged functional group density (meq /
m² ) Is more specifically determined by the following method
Value. First, the material using any of the above methods
Measure the amount of charged functional groups per unit weight (meq / g)
Determine. Next, the specific surface area per unit weight (m² /
g) is measured by mercury intrusion method, BET method, etc.
Divide the amount of charged functional groups per unit weight of the material with the value.
Chargeable functional group amount per unit surface area of material, that is, charge
The functional functional group density is calculated. Specific surface per unit weight of material
Product (m² / G) when measuring by mercury intrusion method
Silver porosimeter (Shimadzu Corporation, Pore Sizer 9320
Or equivalent device) with a pressure range of 0.1-180 psia
Measure with In the leukocyte removing material of the present invention, basic
In addition to functional groups and acidic functional groups, especially hydrophilic functional groups
It is preferable to introduce into the material surface. Of hydrophilic functional groups
Introducing the material surface makes it easy to get wet when it comes in contact with blood
Effective in preventing blood channeling
It is. Such hydrophilic functional groups include hydroxy
Group, amide group, and ethylene oxide chain.
Specific examples of chemical species having a hydrophilic functional group include 2-hydride
Roxyethyl (meth) acrylate, 2-hydroxypropyl
Lopyl (meth) acrylate, glycerin mono (meth)
(Meth) acrylic acid derivatives such as acrylate and vinyl
Having a hydroxyl group such as alcohol,
A) Amides such as acrylamide and N-vinylpyrrolidone
Having an alkyl group, mono having an ethylene oxide chain
Methoxytriethylene glycol (meth) a
Chlorate, methoxytetraethylene glycol (medium
E) Alkoxypolyethyleneglycol such as acrylate
And (meth) acrylates. Porous material used in the leukocyte removing material of the present invention
A quality element is one that has pores through which blood can pass.
If there is no limitation in particular, the thing which has any form is also included
Specifically, natural fiber, glass fiber, knitted fabric, non-woven fabric,
Fibrous media such as woven fabrics, porous membranes, and 3D mesh continuous holes
And sponge-like structure
And sponge-like structures are particularly preferred. Non-woven
The average fiber diameter is 0.
1 to 3.0 μm, preferably 0.5 to 2.0 μm
More preferably, it should be 0.5 to 1.5 μm.
Yes. The average pore diameter is 2 to 20 μm, preferably 2 to 1.
Desirably 5 μm, more preferably 2 to 10 μm
That's right. Fibers with an average fiber diameter of less than 0.1 μm are difficult to manufacture
If the average pore size is less than 2 μm, blood cells
It is not preferable because it is difficult to enter the part. Average fiber diameter is 3.0
When it exceeds μm, and when the average pore diameter exceeds 20 μm,
Amount of material to ensure sufficient surface area for leukocytes to adhere
This is not preferable because it must be increased. Continuous hole
When using a sponge-like structure as a filter material
Preferably has an average pore size of 2-20 μm,
Preferably 2 to 15 μm, more preferably 2 to 10 μm
It is desirable that When the average pore diameter is less than 2 μm
This is not preferable because it is difficult for blood cells to enter the material. Also
Surface area where leukocytes adhere when the average pore size exceeds 20 μm
The amount of material must be increased to ensure sufficient
This is not preferable. The average fiber diameter in the present invention is the following:
The value obtained according to the following procedure. That is, from the base material
Sampling the part that is recognized as qualitatively uniform
Take a picture using a child microscope. When sampling
Thus, the effective filtration cross-sectional area of the fibrous body is 0.5% on one side.
Divide by cm squares and run 6 places
Dumb sampling. For random sampling
For example, after specifying an address for each of the above categories, use a random number table.
You can select the necessary categories by using a method such as Also
3 or more preferably for each section
Take 5 or more photos at a magnification of 2500x. Sump
The central part and the vicinity of each ringed section
A total book of fibers taken in that photo
Take pictures until the number exceeds 100. Where the diameter and
Means the width of the fiber in the direction perpendicular to the fiber axis. Measure
The average of the sum of the diameters of all the fibers divided by the number of fibers
The fiber diameter. However, multiple fibers are overlapping,
If the width cannot be measured behind other fibers,
Multiple fibers are melted, resulting in thick fibers
If there is a mixture of fibers with significantly different diameters
In other cases, these data are deleted. Ma
In addition, the average pore diameter of the base material in the present invention is mercury porosimetry.
(Shimadzu Corporation, Pore Sizer 9320 or equivalent)
Device) and measured in the range of 0.1 to 180 psia.
Measure in the pressure range. As a material for the porous element of the present invention,
Is limited if it is difficult to damage blood cells
Various types can be used, organic polymers, no
Examples include organic polymers and metals. Among them, organic polymers
Is a preferred material because of its excellent workability such as cutting. Yes
Examples of the organic polymer include polyurethane and polyacrylate.
Ronitrile, polyvinyl alcohol, polyvinyl aceta
, Polyester, polyamide, polystyrene, poly
Sulfone, cellulose, cellulose acetate, polyester
Tylene, polypropylene, polyvinyl fluoride, polyfluoride
Vinylidene fluoride, polytrifluorochlorovinyl, fluoride
Vinylidene-tetrafluoroethylene copolymer, polyethylene
-Tersulfone, poly (meth) acrylate, butadiene
-Acrylonitrile copolymer, polyether-poly
Amide block copolymer, ethylene-vinyl alcohol
But are limited to the above examples.
It is not a thing. According to the following examples, leukocyte removal of the present invention
The remaining material will be described in more detail. [0024] Example 1 Basic functional groups were added to a 30% ethanol aqueous solution.
Dimethylaminoethyl methacrylate (hereinafter referred to as DM)
(Abbreviated) 1.3% (% by weight) and methacrylate with acidic functional groups
Luric acid (hereinafter abbreviated as MAA) 0.7% (wt%) in total 2
% (Weight%) and add the monomer solution
Prepared. Average fiber made of polyethylene terephthalate
Immerse a non-woven fabric with a fibril diameter of 1.7 μm in this monomer solution,
Nitrogen bubbling removes dissolved gas in the monomer solution to nitrogen
Sealed after replacement, and radiation graft polymerization with γ rays
went. The gamma ray is 3.6 kGy using cobalt 60 as a radiation source.
Irradiated. After γ-irradiation, the nonwoven fabric is washed with methanol at room temperature.
The plate was washed for 2 hours and further washed with warm water at 40 ° C. for 2 hours. Dry
Drying was performed overnight with 40 ° C. warm air. Total chargeability of this nonwoven fabric
Functional group density is 0.072 meq / m² And basic officer
The active group was 0.53 times the acidic functional group. In this way
Filled with non-woven fabric with basic functional groups and acidic functional groups
Filling density 0.18 g / cm^Three , So that the thickness is 1.8 mm
In a container with an effective filtration cross-sectional area of 57 mm x 57 mm
And created a filter. Add 450 ml CPD to 450 ml blood
Within 8 hours after blood collection from 513 ml whole blood prepared
Remove 243 ml of platelet-rich plasma by centrifugation
Manufactured and stored at 4-5 ° C. for 10 days (hemato
Crit 65%) at room temperature until 22-25 ° C.
Average fiber produced by the spunbond method after placing
Non-woven fabric with diameters of 32 μm and 13 μm, average packing density
0.28 g / cm^Three The thickness is 3.5mm.
Created by filling a container with an effective filtration cross-section of 67 mm x 67 mm
To remove micro-aggregates
Then, transfer about 60 ml of the red blood cell preparation to a new blood bag.
And filtered with the above filter. To start filtration
Or filter the red blood cells through the blood circuit
After connecting to the blood bag, hold the blood bag
The pressure was applied and the blood was forced to fill the filter.
After the blood fills the filter, turn the perista pump
Keep flowing at a constant flow rate of 2 ml / min.
When the blood has run out, stop filtering and
Filter the collection bag connected to the flow through the blood circuit
Cut the entire circuit 30-40cm downstream of the blood outlet
The red blood cell preparation in the circuit and collection bag
It was. Unfiltered red blood cell preparation (hereinafter referred to as pre-filter solution)
U) and the volume of collected liquid and white blood cell concentration are measured and the following formula (1)
The leukocyte residual rate was determined according to Leukocyte residual rate = [white blood cell count (recovered solution) × recovered solution volume] / [white blood cell concentration (pre-filtration solution) ) X Liquid volume before filtration] (1) The volume of the pre-filtration solution and the recovered solution is the specific gravity of each weight.
The value was divided by 1.075. In addition, leukocyte concentration in the pre-filtration solution
The measurement of the degree is a diluted solution 10 times with Turku's solution.
Injection into a Barker-Turku hemocytometer and light microscope
To count the white blood cells present in the 4 large sections
Measured. In addition, the measurement of leukocyte concentration in the collected liquid is as follows.
According to the extremely sensitive method shown. A bag containing the recovered liquid
5% Ficoll 400DL EBSS solution
(Referred to as Ficoll solution)
In addition, the collection bag is fixed on the plasma separation stand.
And left to stand for 40 minutes. After standing, remove the sedimented red blood cell layer
Gently collect the supernatant and avoid again
The same operation was repeated. By two operations
The collected supernatant is Corning 25350 centrifuge tube
Dispense into 840 xg, centrifuge for 15 minutes, suck up the sediment
Discard the supernatant with an aspirator.
It was. Each centrifuge tube contains 200 ml of hemolyzed blood (1.145).
% Ammonium oxalate (saline solution)
Mix and discard supernatant with aspirator in the same way as described above
did. Collect the precipitate in a 15 ml centrifuge tube and dissolve.
Add blood to bring the total volume to 15 ml, then bring to room temperature for 10 minutes
Allow to stand, centrifuge at 468 × g for 10 minutes, including sediment.
5 ml remained and the supernatant was discarded. Thoroughly contain the liquid containing the investigation
After stirring to make a single cell suspension, fluorescent staining solution (69.
9mg / 1 acridine orange solution)
Was stirred. Use this solution for improved Neubauer blood cell count
Injected into 6 plates, large section 10 using epi-illumination fluorescence microscope
White blood cells present in 8 compartments were counted. This county
The leukocyte concentration in the collected solution is calculated from the measured value according to the following formula (2).
I put it out. White blood cell concentration (recovered solution) =Count value x (1/108) x 10 ⁴ × (1 / 0.55 (2) The underlined part is finally 0.
The leukocyte concentration (cells / ml) in the liquid concentrated to 5 ml.
This is divided by 0.55 to calculate the leukocyte concentration.
Dividing by 0.55 means that leukocytes are removed using Ficoll solution.
This is because the recovery rate at the time of recovery is 55%. This
As a result, the leukocyte residual rate was 10^-4.3Met. [0028] [Comparative Example 1] DM in a 30% aqueous ethanol solution with 2% DM
%) And prepare a monomer solution
It was. The same non-woven fabric as in Example 1 is immersed in this monomer solution,
Γ-ray graft polymerization, washing and drying were performed in the same manner.
The basic functional group density of the obtained nonwoven fabric is 0.051 meq.
/ M² Met. As a result of measuring the density of acidic functional groups, detection
It was below the limit. Treating blood with the same operation as in Example 1
As a result, the residual leukocyte rate was 10^-3.2Met. [0029] [Comparative Example 2] 2% MAA in 30% ethanol aqueous solution
Add the monomer solution to a concentration of (% by weight).
Made. The same nonwoven fabric as in Example 1 is immersed in this monomer solution.
In the same way, γ-ray graft polymerization, washing and drying are performed.
It was. The density of the acidic functional group of the obtained nonwoven fabric is 0.093 me.
q / m² Met. As a result of measuring the base functional group density,
It was below the limit. Blood was treated in the same manner as in Example 1.
As a result, the leukocyte residual rate was 10^-3.0Met. [0030] Example 2 2-hydroxy in 30% ethanol aqueous solution
Ethyl methacrylate (hereinafter abbreviated as HEMA) 1% (heavy
%), DM 1.3% (weight%), and MAA 0.7% (weight)
%) To a total concentration of 3% (weight%)
A monomer solution was prepared. Example 1 was added to this monomer solution.
Immerse the same nonwoven fabric with γ-ray graft polymerization in the same operation,
Washing and drying were performed. Total chargeable functional groups of the resulting nonwoven fabric
Density is 0.059 meq / m² And the basic functional group is
It was 0.55 times the acidic functional group. The same operation as in Example 1
When blood was processed with the product, the residual leukocyte rate was 10^-4.6so
there were. [0031] Example 3 3-Dimethylaqua in 30% ethanol aqueous solution
Mino-2-hydroxypropyl methacrylate (hereinafter D
Abbreviated as MHP) and 2-sulfoethyl methacrylate (hereinafter referred to as MHP).
1% (weight%) of each 2% (weight)
%) To prepare a polymerization solution. This
The same nonwoven fabric as in Example 1 was immersed in the polymerization solution of
Then, γ-ray graft polymerization, washing and drying were performed. Obtained
The total charged functional group density of the woven fabric is 0.053 meq / m.² so
Yes, the basic functional group was 1.1 times the acidic functional group.
When blood was treated in the same manner as in Example 1, leukocytes
Survival rate is 10^-4.5Met. [0032] The leukocyte removing material of the present invention is porous.
A wide range of materials for introducing charged functional groups
Can be used at low cost and with excellent stability
The And as shown in the examples, compared to conventional materials
Excellent leukocyte removal ability.

Continued from front page (58) Fields surveyed (Int.Cl. ⁷ , DB name) A61K 35/14 A61M 1/34 A61M 1/36 B01J 20/26

Claims (1)

(57) Claims 1. A base material for removing leukocytes is a porous element, and a basic functional group and an acidic functional group are introduced into a surface portion of the base material, Surface basic functional groups and acidic agents
The total chargeable functional group density of the active group is 10 per surface area of the material.
^{-4 to 5} meq / m ² and the basic surface of the substrate surface
A leukocyte-removing material characterized in that the functional group density is 0.05 to 20 times the acidic functional group density .