JP2001198213A - Minute aggregate removing filter medium - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a minute aggregate removing filter medium extremely low in erythrocyte adsorbing capacity and extremely high in minute aggregate removing capability and a method for removing minute aggregate from erythrocyte-containing blood in an extremely efficient manner. SOLUTION: The minute aggregate removing filter medium comprises a fibrous porous base material having a mean fiber diameter of 8 - below 50 μm and containing a nonionic hydrophilic portion and a basic portion on its surface and characterized in that the hydrophilic portion has a hydrophilic basic group positioned on a terminal side from the basic portion. An apparatus including at least an introducing port, a filter containing the filter medium and a lead-out port is used to remove minute aggregate from erythrocyte- containing blood.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a filter material for removing microaggregates from erythrocyte-containing blood such as a concentrated erythrocyte preparation containing microaggregates, and a filter material for removing the microaggregates. The present invention relates to a method for removing microaggregates using the method.

[0002]

2. Description of the Related Art In the field of blood transfusion, a whole blood product obtained by adding an anticoagulant to blood collected from a donor is transfused. The so-called component blood transfusion in which blood components are separated and the blood components are transfused has been generally performed. Component transfusions include erythrocyte transfusions, platelet transfusions, plasma transfusions, etc., depending on the type of blood component required by the recipient.The blood component preparations used for these transfusions include erythrocyte preparations, platelet preparations, and plasma preparations. and so on.

In recent years, so-called leukocyte-removed transfusion, in which a blood product is transfused after removing leukocytes mixed in the blood product, has become widespread. This may include relatively minor side effects such as headache, nausea, chills, and non-hemolytic fever associated with blood transfusions, or severe allergens such as alloantigen sensitization, viral infection, and GVHD after blood transfusion that have a serious effect on the recipient. It has been clarified that such adverse side effects are mainly caused by leukocytes mixed in blood products used for blood transfusion.

In order to prevent relatively minor side effects such as headache, nausea, chills and fever, it is necessary to remove leukocytes from blood products until the residual ratio becomes 10 ^-1 to 10 ^-2 or less. It is said. In addition, it is said that leukocytes should be removed until the residual ratio becomes 10 ^-4 to 10 ^-6 or less in order to prevent allergen sensitization and virus infection, which are serious side effects.

[0005] Methods for removing leukocytes from blood products include:
It is roughly divided into a centrifugal separation method that separates and removes white blood cells using the difference in specific gravity of blood components using a centrifugal separator, and a filter material composed of a fiber material such as a nonwoven fabric or a porous material having continuous pores. There are two types of filter methods to remove leukocytes. A filter method for removing leukocytes by adhesion or adsorption is currently popular because it has advantages such as excellent leukocyte removal ability, simple operation, and low cost.

In general, in a concentrated red blood cell preparation, during centrifugal operation performed during preparation of the preparation and during storage of the preparation, a part of proteins and blood cell components aggregate to form microaggregates. The microaggregates are approximately 200 μm or less in size. When removing leukocytes from a blood product containing such microaggregates, if it is intended to directly treat with a filter material having excellent leukocyte removal ability, the leukocyte removal filter has a small pore diameter, so that the upper layer portion of the filter material is minute. Aggregates can cause clogging, which makes it difficult to process a desired amount of blood product to completion. EP 0155003B
1, WO93 / 03740, JP-A-6-247762 (Asahi Medical), and USP 4,925,572 (Paul Corporation) arrange a coarse filter material for removing aggregates upstream of a leukocyte removal filter material. By doing so, a technical means for avoiding that the leukocyte removal filter material is clogged with microaggregates has been disclosed,
At present, it is generally employed in leukocyte removal filter devices.

However, microaggregates are different from leukocytes,
The size distribution is also wide, and the components are proteins and blood cell components aggregated in various forms, and the surface properties are also various. Therefore, even if a filter material for removing microaggregates as in the prior art is used, the removal of microaggregates is not sufficient.

In recent years, new demands have been made on the market for a leukocyte-removing filter for processing a desired amount of red blood cell-containing blood in a shorter time than before. However, in the technical means for preventing the leukocyte-removing filter material from being clogged with micro-aggregates by arranging a coarse filter material for removing aggregates as described above in the upstream, the filter material is removed by the micro-aggregate removal filter materials. The microaggregates that could not be reached reach the upper part of the leukocyte removal filter material arranged downstream and are captured and accumulated, the processing speed gradually decreases, and the desired amount of red blood cell-containing blood is efficiently filtered to the end. Was sometimes difficult to do. Also,
In particular, when filtering red blood cell-containing blood having many microaggregates due to a long storage period, etc., microaggregates may extremely clog in the upper layer of the leukocyte removal filter material, and a desired amount of red blood cells may be obtained. It may be difficult to filter the contained blood to completion.

As one of technical means capable of coping with such a case, it is conceivable to increase the amount of the microaggregate removal filter material to enhance the ability to remove microaggregates. However, in recent years, in the market, while improving the recovery rate of useful components, it has become unnecessary to recover the useful components remaining in the filter and the circuit with physiological saline or air, thereby saving labor. There is a great demand for a leukocyte removal filter. On the other hand, in particular, blood, which is a raw material of blood products, is often valuable blood provided by blood donation in good faith. Blood that remains in the leukocyte-removing filter and cannot be collected is discarded together with the filter as it is and is wasted. Therefore, it is extremely significant to improve the recovery rate of useful components. The method of increasing the amount of the microaggregate removal filter material as described above increases the volume of the entire leukocyte removal filter device, and increases the amount of blood product remaining in the filter. Is not preferred.

Further, as another technical means for improving the ability to remove microaggregates without increasing the volume of the microaggregate removal filter material, it is conceivable to use a fibrous filter material having a smaller fiber diameter. However, in such a filter material, microaggregates are concentrated and trapped in the upper layer portion of the microaggregate removal filter material, causing clogging, and as a result, it is difficult to process a desired amount of blood to the end. Therefore, it is not suitable for removing microaggregates.

[0011] As described above, it is difficult to provide a microaggregate removal filter material for a leukocyte removal filter that has a high ability to remove microaggregates and can maintain a high blood product processing speed by the conventional technical means. Met.

[0012] In recent years, for the purpose of maintaining high quality of blood products, a system has been studied in which a blood center is used to remove leukocytes from a blood product using a leukocyte removal filter at a blood center and then preserves the blood product. In such cases, white blood cells and platelets, which are considered to be one of the components of the microaggregate, are removed before storing the blood product, so the amount of microaggregate generated during storage of the blood product at the blood center However, the formation of microaggregates during storage is unavoidable. When a blood product stored at a blood center is transfused into a patient at a hospital, side effects may be caused by microaggregates contained in the blood product. Therefore, it is preferable to filter and remove microaggregates contained in blood products at the time of blood transfusion at a hospital. However, since this blood product has been once filtered through a leukocyte removal filter, blood component loss has already occurred, and it is required to minimize the blood component loss in a filter that filters microaggregates. In this case, if a microaggregate removal filter filled with a filter material having a high ability to remove microaggregates is used, the volume of the filter device can be reduced, and the amount of blood remaining in the filter device and cannot be collected can be reduced. Very preferred because it can be minimized.

Furthermore, the present inventors have previously used a filter material having a hydrophilic portion and a basic portion independently on its surface, for example, a polymerizable monomer having a dialkylamino group and a polymerizable monomer having a hydroxyl group. Provided a leukocyte removal filter in which a fibrous porous base material is coated with a polymer (WO93 / 03740 and JP-A-6-247762). However, it has been studied to filter a concentrated erythrocyte preparation having a low plasma protein concentration with the filter material. As a result, a phenomenon in which the microaggregate removal rate was reduced was observed. When the filter material having such a phenomenon was observed with an electron microscope, it was observed that a large amount of red blood cells adhered to the surface of the filter material. It is thought that a large amount of red blood cells adhered to the filter material, which caused red blood cells to be adsorbed to the adsorption seats on the surface of the filter material where micro-aggregates should be adsorbed, preventing the micro-aggregates from adsorbing to the filter material surface. Can be In the above-mentioned polymer, it was found that the adhesion of erythrocytes can be suppressed by reducing the content of the dialkylamino group, but in that case, it is difficult to improve the ability to remove microaggregates as expected.

[0014]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems of the prior art. That is, the first object of the present invention is to provide a high-density red blood cell preparation containing microaggregates, in which the microaggregate removal rate is extremely high, the blood product processing speed can be maintained at a high state, and the flow of red blood cell-containing blood is extremely good. It is an object of the present invention to provide a filter material for removing microaggregates from erythrocyte-containing blood. A second object of the present invention is to provide a method for removing microaggregates with extremely high efficiency while suppressing adsorption of red blood cells from erythrocyte-containing blood such as a concentrated erythrocyte preparation containing microaggregates. . Further, a third object of the present invention is to provide a filter for removing microaggregates from blood products, which minimizes loss of blood components in the filter for removing microaggregates.

[0015]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have found that at least the surface of the fibrous porous substrate has a nonionic hydrophilic portion and a base. The present inventors have found that the above-mentioned problems can be solved by using a filter material having a hydrophilic basic group containing a hydrophilic moiety and have reached the present invention. The present invention surprisingly has an effect of suppressing the adsorption of erythrocytes by introducing a hydrophilic basic group having such a structural characteristic into the surface of the filter material, and has an effect on microaggregates. The present inventors have found that the filter material exhibits extremely high affinity, has a high passage rate of red blood cells, which is a useful component, and has extremely low passage resistance.

That is, the present invention provides (1) a filter material for removing microaggregates from erythrocyte-containing blood containing microaggregates, wherein the filter material has an average fiber diameter of 8
a fibrous porous body having a size of at least 50 μm and less than 50 μm, and having at least a hydrophilic basic group containing a nonionic hydrophilic portion and a basic portion on the surface thereof; , Wherein the hydrophilic portion is located on the terminal side of the basic portion, (2) at least one hydrophilic portion is located at the extreme end of the hydrophilic basic group. (1) The filter material for removing microaggregates according to (1), (3) the filter material for removing microaggregates according to (1) or (2), wherein the hydrophilic portion is a hydroxyl group, and (4) the basic portion. The filter material for removing microaggregates according to any one of the above (1) to (3), which is a secondary and / or tertiary amino group, and (5) the above (1), wherein the hydrophilic basic group is a hydroxyalkylamino group. )) Micro-aggregate removal filter material, (6) Any of the above (1) to (5), wherein a monomer containing a hydrophilic basic group and / or a polymer containing a monomer containing a hydrophilic basic group as a component is introduced on the surface of the fibrous porous substrate. (7) The microaggregation according to (6) above, wherein the polymer containing a monomer containing a hydrophilic basic group as a component is a copolymer with a monomer containing no hydrophilic basic group. Material removal filter material. (8) The polymerizable monomer containing a hydrophilic basic group is a (meth) acrylic acid derivative as described in (6) or (7) above.
(9) The density of hydrophilic basic groups per unit surface area of the filter material is 0.1 μe.
The above (1), which is not less than q / m ^{2 and} less than 1000 μeq / m ^2.
A microaggregate removal filter material according to any one of (8) to (8),
(10) The filter material according to any one of (1) to (9), wherein the number of the basic portions with respect to the number of the hydrophilic portions is 0.01 to 0.5 on the surface of the filter material. , (11) at least 1) an inlet, 2) a filter including the microaggregate removal filter material of (1), and 3) a red blood cell containing microaggregates from the inlet using an apparatus including an outlet. A method of removing microaggregates from erythrocyte-containing blood containing microaggregates, comprising injecting blood and collecting the liquid filtered by the filter from an outlet, and (12) a filter material for removing microaggregates A method for removing microaggregates from erythrocyte-containing blood containing microaggregates as described in (11) above, wherein a leukocyte-removing filter material is disposed downstream of the method.

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. The microaggregate removal filter material of the present invention is a porous substrate that forms the physical structure of the filter material, that is, a fibrous porous substrate having an average fiber diameter of 8 μm or more and less than 50 μm, and a surface of the substrate. A filter material having a hydrophilic basic group and a hydrophilic portion located at a terminal side of the hydrophilic basic group from the basic portion. A fibrous porous substrate is suitable as the substrate of the microaggregate removal filter material of the present invention.

The average fiber diameter referred to in the present invention is defined as the diameter of at least 100 fibers selected at random by taking photographs of the fibers constituting the fibrous porous substrate with a scanning electron microscope. , Are values obtained by numerically averaging them. When the average fiber diameter of the fibers constituting the fibrous porous base material is less than 8 μm, the fine agglomerates are concentrated and trapped in the upper layer of the filter material because the pore size and open pore size of the filter material are small. Cause clogging. For this reason, when processing a desired amount of blood, the processing speed is reduced halfway, making it difficult to efficiently process red blood cell-containing blood to the end, which is not suitable for the purpose of the present invention. Further, when the average fiber diameter of the fibers constituting the fibrous porous substrate is 50 μm or more, the surface area of the filter material per unit volume is small, and the frequency of contact of the fine aggregates with the filter material is drastically reduced. For this reason, the amount of adsorption is reduced. For this reason, it is difficult to sufficiently remove microaggregates in the blood containing erythrocytes to be filtered, which is not suitable for the purpose of the present invention. The fibrous porous substrate suitable for the present invention has an average fiber diameter of 8 μm or more and less than 50 μm, preferably an average fiber diameter of 10 μm or more and less than 40 μm, and most preferably an average fiber diameter of 12 μm or more and 35 μm.
Is less than.

Note that the present inventors have disclosed WO99 / 1130.
4 provided a leukocyte removal filter comprising a fibrous porous substrate having at least a hydrophilic basic group containing a nonionic hydrophilic portion and a basic portion on its surface, and the fiber diameter was 0.001. 〜3.0 μm. This fiber diameter is suitable for leukocyte removal, but there is a problem that clogging occurs when used for filtration of blood products containing microaggregates.

As the fibrous porous substrate suitable for the present invention, any of a fiber aggregate composed of long fibers and a fiber aggregate composed of short fibers is suitable. In particular, a fiber aggregate made of long fibers is more preferable because of less outflow foreign matter and low production cost. Preferred forms of the fiber aggregate include a nonwoven fabric, a woven fabric, and a knitted fabric, and a nonwoven fabric is particularly preferred because of its high porosity. As the material of the fiber assembly, any material can be used as long as it can form a nonwoven fabric, woven fabric, or knitted fabric such as polyester, polyolefin, polyamide, polyurethane, polyacrylonitrile, polystyrene, cellulose, or cellulose acetate.

The surface of the microaggregate removal filter material of the present invention has a hydrophilic basic group containing a nonionic hydrophilic part and a basic part.
The hydrophilic part is located at a terminal side of the basic part. Further, on the surface of the filter material of the present invention, as long as it has at least one hydrophilic portion on the terminal side of the hydrophilic basic group, a hydrophilic portion is provided on a portion other than the terminal side of the hydrophilic basic group. Even if it has, it is included in the form of the filter material of the present invention. Here, "having a hydrophilic basic group on the surface of the fibrous porous substrate" means that a monomer or polymer containing a hydrophilic basic group is covalently bonded, ion-bonded, physically adsorbed, embedded, It means that it is introduced so as not to fall off on the surface of the fibrous porous substrate forming the filter material by any known method such as precipitation insolubilization,
Alternatively, it is determined that a fibrous porous substrate that forms a filter material with a polymer material having a hydrophilic basic group is formed, and that the hydrophilic basic group is present on the surface of the fibrous porous substrate. To tell. Either case is included in the form of the microaggregate removal filter material of the present invention.

Furthermore, the term "hydrophilic basic group" as referred to in the present invention refers to the terminal of the chemical structural formula on the surface of the filter material.
A portion at a position longer than a distance (length) from a portion holding a hydrophilic basic group (hereinafter also referred to as a holding portion) to a basic portion. Here, the holding portion refers to a portion where the hydrophilic basic group is in contact with the fibrous porous substrate forming the filter material. Specifically, for example, when a hydrophilic basic group itself, or a monomer or polymer containing a hydrophilic basic group is introduced into the fibrous porous substrate forming the filter material by covalent bond or ionic bond, etc. Is a portion bonded to the fibrous porous substrate as a holding portion. Further, when a polymer having a polymerizable monomer containing a hydrophilic basic group as a constituent component is physically adsorbed by coating or the like on the surface of a fibrous porous base material forming a filter material, The main chain is the holding part. When the filter material is formed of a polymer material having a hydrophilic basic group as a side chain, a portion where the side chain is bonded to the main chain of the polymer material is defined as a holding portion.

That is, the microaggregate removal filter material of the present invention refers to microaggregates, erythrocytes, leukocytes, etc. contained in blood rather than the basic portion when the filter material is brought into contact with blood containing erythrocytes. A filter material having a hydrophilic basic group of a specific structure on the surface, in which at least one hydrophilic portion is arranged at a position where it is more likely to come into contact with blood cells.

Further, in the hydrophilic basic group of the present invention,
More preferably, the hydrophilic moiety is located at the extreme end of the hydrophilic basic group. This is because by disposing the hydrophilic portion at the extreme end of the hydrophilic basic group, the effect of further suppressing the attachment of red blood cells tends to increase.

Examples of the nonionic hydrophilic moiety referred to in the present invention include a hydroxyl group, an amide group, an ether group, a nitro group, a nitroso group, a sulfoxide group, a sulfonyl group, a phosphoryl group, a phospho group, a carboxamide, and a sulfone group. Examples include amide, thioamide, cyano group, cyanate, thiocyanate, and isothiocyanate.
Among these, a hydroxyl group, an amide group, or an ether group, which is particularly chemically stable and highly hydrophilic, is preferable, and a hydroxyl group or a polyethylene oxide chain having a repeating number of ethylene oxide units of 2 to 10 is more preferable. Is most preferred.

The basic moiety in the present invention is a moiety having a positive charge. Since the basic portion has a positive charge, it has the effect of improving the affinity of the microaggregate by electrostatic interaction. Specific examples of the basic moiety that can be used in the present invention include a secondary amino group, a tertiary amino group, and an amino group of a quaternary ammonium group, and a skeleton such as pyrrole, pyrazole, pyrrolidine, or piperidine. And a nitrogen-containing heterocyclic group. Among them, secondary and tertiary amino groups are preferable because they are chemically stable and have high safety as a medical device.

The hydrophilic basic group referred to in the present invention is a functional group having a structure containing the above-described nonionic hydrophilic portion and basic portion, and more specifically, the following formula (1) or ( This refers to a functional group having a structure represented by 2).

Embedded image R ¹ : a structure containing a hydrophilic part R ² : a structure containing a hydrophilic part or an alkyl group,
Structure without a hydrophilic part such as hydrogen

Embedded image R ¹ : a structure containing a hydrophilic portion R ² , R ³ : a structure containing a hydrophilic portion or an alkyl group,
Structure without a hydrophilic part such as hydrogen

Among such hydrophilic basic groups, a monohydroxyalkylamino group, a bis (hydroxyalkyl) amino group, a bis (hydroxyalkyl) amino group in which at least one or more hydroxyl groups are bonded to a positively charged nitrogen atom via a carbon atom. Alternatively, a tris (hydroxyalkyl) amino group is preferable,
Further, the number of carbon atoms in the alkyl moiety in the hydroxyalkylamino group structure is preferably 1 or more and 10 or less, more preferably 1 or more and 5 or less.

The method for introducing the hydrophilic basic group of the present invention to the surface of the porous substrate forming the filter material is not particularly limited, and various known methods can be used. For example, a method of introducing a monomer having a hydrophilic basic group by a grafting method such as radiation grafting or plasma grafting, a method of coating a polymer having a hydrophilic basic group, a method of coating a base having an active group and a hydrophilic base with a hydrophilic base. And a method of reacting a chemical species such as a monomer or polymer having an ionic group.

Examples of the polymerizable monomer having a hydrophilic basic group that can be used in the grafting method or the polymer coating method include N-mono (hydroxyalkyl) aminoethyl (meth) acrylate and N, N-bis (hydroxyalkyl). ) Aminoethyl (meth) acrylate,
N-mono (hydroxyalkyl) amino-2-hydroxypropyl (meth) acrylate, N, N-bis (hydroxyalkyl) amino-2-hydroxypropyl (meth) acrylate, N- (methoxypolyoxyethyl)
(Meth) acrylic acid derivatives such as aminoethyl (meth) acrylate, N, N-bis (methoxypolyoxyethyl) aminoethyl (meth) acrylate, styrene derivatives such as N-hydroxyaminostyrene, N- (hydroxyalkyl) amino And vinyl derivatives such as ethylene. In this specification, (meth) acrylate represents acrylate or methacrylate, and (meth) acrylic acid represents acrylic acid or methacrylic acid. Among the monomers exemplified here, for ease of synthesis, and excellent handleability,
A derivative of (meth) acrylic acid is preferable, and a derivative of (meth) acrylic acid having a mono (hydroxyalkyl) amino group or a bis (hydroxyalkyl) amino group is more preferable.

When modifying the surface of the fibrous porous substrate forming the filter material by the grafting method or the polymer coating method, another polymerizable monomer having no hydrophilic basic group may be introduced. . The other polymerizable monomer is not particularly limited, and any polymerizable monomer can be used. However, (meth) acrylic acid typified by hydroxyethyl (meth) acrylate and methyl (meth) acrylate is used because of its excellent handleability. Preferably, it is a derivative.

Further, when coating is carried out using a polymer comprising a polymerizable monomer having a hydrophilic basic group and another polymerizable monomer, the polymer may be a random copolymer, a block copolymer, or an alternating copolymer. For example, random copolymers can be used, but random copolymers are more preferable because of easy polymerization. The type of the polymerizable monomer constituting the above-mentioned copolymer is not particularly limited, but a copolymer composed of two or three types of polymerizable monomers is preferable for reasons such as ease of production. In the case of a copolymer, a copolymer of a polymerizable monomer having a hydrophilic basic group and a monomer having a hydroxyl group is preferable. At this time, the content of the polymerizable monomer having a hydrophilic basic group is preferably at least 5 mol%, more preferably at least 20 mol%.

As another method for introducing a hydrophilic basic group into the surface of the filter material for removing microaggregates of the present invention, a fibrous porous material having an active group such as an epoxy group, a carboxyl group or an acid halide on the surface in advance. A method in which a hydrophilic basic group is introduced by reacting a chemical species having a hydrophilic basic group, such as hydroxyalkylamines represented by diethanolamine, with a substrate. When such active groups do not exist in advance on the surface of the base material, a monomer having an active group, for example, glycidyl (meth) acrylate or (meth) acrylic acid is subjected to a radiation grafting method using γ-ray, electron beam or the like. The method of introducing a polymer having a monomer having an active group as a constituent component into the surface of the fibrous porous substrate or coating the polymer with the polymer may be applied to the surface of the fibrous porous substrate. An active group may be introduced. Among the various methods described above, the grafting method and the polymer coating method are preferable because the operation is relatively simple, and the polymer coating method is particularly preferable because of its excellent productivity.

The density of introduction of hydrophilic basic groups on the surface of the filter material for removing microaggregates of the present invention is 0.1 μeq /
m is preferably ² or more 1000Myueq / m less than ^2. If the introduction density of the hydrophilic basic group is less than 0.1 μeq / m ² , the ability to remove microaggregates tends to decrease, which is not preferable. On the other hand, if it exceeds 1000 μeq / m ² , the cost increases, which is not preferable. More preferably 0.2
μeq / m ² or more 100μeq / m less than ^2, more preferably from 0.5μeq / m ² or more 30 [mu] eq / m ^2.

In the present invention, the introduction density of the hydrophilic basic group on the surface of the filter material is determined by X-ray photoelectron spectroscopy (XPS),
It can be measured by a known method such as Auger electron spectroscopy (AES), secondary ion mass spectrometry (SIMS), and multiple total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Alternatively, the surface of the filter material may be extracted using an appropriate method, and the hydrophilic basic groups contained in the extracted substance may be measured using a known method such as nuclear magnetic resonance spectroscopy (NMR). Further, the introduction density of the hydrophilic basic group may be determined by acid-base titration or dye adsorption method. Among the various methods described above, the dye adsorption method is preferable because the operation is simple. The dye adsorption method is a method in which a dye such as trypan blue having a negative charge is adsorbed to a basic portion in a hydrophilic basic group, and the amount of change in absorbance of the trypan blue solution is used to determine the hydrophilic basicity on the filter material surface. This is a method for quantifying the amount of a group. More specifically, it contains trypan blue, pH
Is prepared as an original solution. Next, an appropriate amount of the original solution was impregnated into the filter material, and the filter material was brought into contact with the filter material at room temperature for 16 hours or more. The supernatant solution after impregnating the filter material with the original solution was measured with 578 nm visible light. The introduction density per unit weight of the filter material or per unit surface area of the filter material is calculated from the difference between the absorbance of the supernatant and the absorbance of the supernatant.

When the density of introduction of the hydrophilic basic group per unit weight of the filter material is calculated by the dye adsorption method or other various methods described above, and this is converted into the density of introduction per unit surface area of the filter material. Can be determined by measuring the surface area per unit weight of the filter material by the mercury intrusion method and dividing the density of introduction of the hydrophilic basic group per unit weight of the filter material by this value. The surface area per unit weight of the filter material by the mercury intrusion method is measured by the following procedure.

First, an appropriate amount is sampled from a portion of the filter material which is considered to be substantially uniform, and its weight (W) is measured. Next, the sampled filter material was set in a mercury porosimeter (Poresizer 9310 PC2A type, Shimadzu Corporation or an equivalent device), the surface area (A) was measured in a pressure range of 0.1 to 400 psia, and the following formula ( The surface area per unit weight of the filter material is determined from I). Surface area per unit weight = A / W (m ² / g) (I) However, sampling was performed from three or more locations of the filter material, and the average value of the values obtained for each sampled location was calculated as the surface area per unit weight of the filter material. And

On the surface of the filter material for removing microaggregates according to the present invention, the number of basic parts with respect to the number of nonionic hydrophilic parts is preferably 0.01 or more and 0.5 or less. The number of basic moieties to hydrophilic moieties is 0.
If it is less than 01, there is a possibility that a sufficient effect of improving the ability to remove microaggregates may not be obtained, which is not preferable. On the other hand, if the number of basic parts exceeds 0.5 relative to the number of hydrophilic parts, the amount of red blood cells adsorbed on the surface of the filter material for removing microaggregates tends to increase, which is not preferable. The number of basic moieties with respect to the number of more preferable hydrophilic moieties is 0.03 or more and 0.5 or less. However, when the nonionic hydrophilic portion is a polyethylene oxide chain, one polyethylene oxide chain is used as one hydrophilic portion regardless of the repeating unit of the ethylene oxide chain, that is, regardless of the length of the polyethylene oxide chain. I will count as.

A second object of the present invention is to provide a method for removing microaggregates from erythrocyte-containing blood such as a concentrated erythrocyte preparation containing microaggregates with very high efficiency while removing erythrocytes. To provide. As a result of intensive studies conducted by the present inventors, at least a device having a microaggregate removal filter material of the present invention properly filled in a container having an inlet and an outlet, the erythrocyte-containing blood containing the microaggregate is removed. It has been found that the second problem can be achieved by filtering and collecting the filtered liquid. In addition, the present inventors have also found that this method can achieve the problem of removing microaggregates with little loss of effective blood components such as red blood cells.

The erythrocyte-containing blood to be filtered by the apparatus filled with the microaggregate removal filter material of the present invention includes a concentrated erythrocyte preparation. By filtering such blood containing erythrocytes with a device filled with the filter material for removing microaggregates of the present invention, microaggregates can be efficiently removed. Further, erythrocytes such as a concentrated erythrocyte preparation can be reduced to 1 × 10 6 ^For erythrocyte-containing blood containing at a concentration of ⁹ cells / mL or more, it is possible to give a good result that also suppresses erythrocyte adhesion.

Further, among the erythrocyte preparations, erythrocyte-containing blood having a plasma protein concentration of 25 g / L or less, or even 10 g / L or less, is filtered using a device filled with the microaggregate removal filter material of the present invention. A remarkable effect can be exhibited with respect to the suppression of adhesion.

As described above, the microaggregate removal filter material of the present invention has extremely high affinity for microaggregates,
In addition, since it also has the effect of suppressing red blood cell adhesion, it is possible to achieve high microaggregate removal ability and good blood flow. Furthermore, the combination of the microaggregate removal filter material of the present invention and the leukocyte removal filter allows a desired amount of red blood cell-containing blood to be processed in a shorter time than a conventional leukocyte removal filter device. This is because the use of the microaggregate removal filter material of the present invention prevents clogging of microaggregates in the upper layer of the leukocyte removal filter material, thereby avoiding a reduction in processing speed and increasing the blood product to the end. This is because processing can be performed efficiently at a processing speed. That is, on the downstream side of the filter containing the microaggregate removal filter material of the present invention, a filter in which a filter containing a known leukocyte removal filter material is arranged, is filled in an apparatus including at least an inlet and an outlet,
By injecting erythrocyte-containing blood containing microaggregates from the inlet and collecting the liquid filtered by the filter from the outlet, the blood product can be processed efficiently at a high processing rate to the end.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the scope of the present invention is not limited only to these Examples. In the following Examples or Comparative Examples, the microaggregate removal rate was determined as follows. Measure the concentration of microaggregates of the concentrated erythrocyte preparation before filtration (hereinafter, referred to as pre-filtration solution) and the recovered concentrated erythrocyte preparation (hereinafter, referred to as collection liquid), the volume of the pre-filtration liquid and the volume of the collection liquid. Then, the microaggregate removal rate (%) was determined according to the following equation. Micro-aggregate removal rate (%) = {(micro-aggregate concentration in recovery liquid × recovery liquid volume) / (micro-aggregate concentration in pre-filtration liquid × volume of pre-filtration liquid)} × 100 The volume of the collected liquid was a value obtained by dividing each weight by the specific gravity (1.075) of the blood product. The microaggregate concentrations of the pre-filtration liquid and the recovered liquid were determined by the following operations. A nylon mesh having an opening diameter of 40 μm was cut out into a circular shape having a diameter of 25 mm, and loaded into a filter folder. Blood was slowly filtered through this filter using a syringe. The filtered blood volume was 2 mL for the pre-filtration solution and 20 mL for the recovered solution. After filtration, the nylon mesh was taken out of the filter folder, the number of captured microaggregates was counted by microscopic observation, and the microaggregate concentrations of the pre-filtration solution and the recovered solution were measured.

[0044]

Example 1 N, N-bis (hydroxyethyl) amino
-2-Hydroxypropyl methacrylate (GA)
Adult toluene (purity 99% (GC), manufactured by Wako Pure Chemical Industries, Ltd.) in, added to a glycidyl methacrylate at a concentration of 1 mol / L, further to the solution, consisting of diethanolamine concentration of 1.1 mol / L Then, the mixture was gradually added dropwise so as not to generate heat, and the total amount was adjusted to 500 mL.
Hydroquinone monomethyl ether (M
After adding EHQ) to a concentration of 0.005 mol / L, the mixture was reacted at 60 ° C. for 6 hours. The solution after completion of the reaction is purified by distillation under reduced pressure, fractional extraction, liquid chromatography, and the like, to give N, N-bis (hydroxyethyl) amino-2-hydroxy having a hydroxyethylamino group which is a hydrophilic basic group. Propyl methacrylate (hereinafter referred to as GA) was synthesized.

Synthesis of Coating Polymer Next, the above GA and 2-hydroxyethyl methacrylate (hereinafter, referred to as HEMA) were placed in ethanol (special grade).
Was synthesized by ordinary solution radical polymerization. As the polymerization conditions, the monomer concentration in ethanol was set to 1 mol / L, V-65 (manufactured by Wako Pure Chemical Industries, Ltd.) was added as a polymerization initiator to a concentration of 0.01 mol / L, and 50 ° C under a nitrogen atmosphere. For 4.5 hours. After the completion of the polymerization, the reaction solution was dropped into distilled water to precipitate a polymer, and then freeze-dried. When the GA content in the obtained polymer was measured by acid-base titration, the polymer contained about 5 mol% of a GA component (hereinafter, referred to as “GA content”).
This polymer is called HGA-5).

Preparation of the filter device The device has an inlet and an outlet for blood and has an effective filtration area of 67 m.
A polyester nonwoven fabric having an average fiber diameter of 32.2 μm manufactured by a spun bond method and having a thickness of 1.0 mm is placed on the blood introduction port side in a mx67 mm container, and the average fiber diameter is 13. A 1 μm polyester nonwoven fabric is arranged at a thickness of 0.7 mm, and the packing density is 0.28 g / c.
m ³ . HGA-5 polymer was added to 0.
An ethanol solution dissolved at a concentration of 1% by weight was filled in this container and allowed to stand for 1 minute. Thereafter, excess liquid was blown off with nitrogen gas, and further vacuum-dried at 60 ° C. for 16 hours to produce a filter device. The filter material for removing microaggregates in the prepared filter device had hydrophilic basic groups on its surface at an average introduction density of 1.9 μeq / m ² .

Filtration of erythrocyte-containing solution A 400 mL blood solution was used as an anticoagulant in a 56 mL CPD solution (composition: sodium citrate 26.3 g / L, citric acid 3.27 g / L, glucose 23.20 g / L, diphosphate). After centrifuging 456 mL of whole blood prepared by adding sodium hydrogen dihydrate (2.51 g / L), plasma and buffy coat were removed, and 95 mL of M was used as a red blood cell preservation solution.
AP solution (composition: sodium citrate 1.50 g / L, citric acid 0.20 g / L, glucose 7.21 g / L, sodium dihydrogen phosphate dihydrate 0.94 g / L, sodium chloride 4.97 g / L) L, 0.14 g / L of adenine, 14.57 g / L of mannitol) to prepare a concentrated erythrocyte preparation (haematocrit is about 63 to 64%, plasma protein concentration is about 0.9 to 1.2 g / L), Stored at 4 ° C. for 20 days. 325 g of the concentrated erythrocyte preparation was allowed to stand at room temperature of 24 ° C., and was filtered at a height of 0.3 m using a filter coated with HGA-5. After the filter was filled with blood and filtration was started, filtration was performed until no blood remained in the blood bag, and the filtered blood was collected. The filtration time at this time was from when the blood began to flow out of the outlet of the filter to when the blood in the blood bag was exhausted. As a result, the microaggregate removal rate was 69%.
Further, when the filter material after blood filtration was observed with an electron microscope, there was no adsorption of red blood cells to the filter material and no clogging of the filter.

[0048]

Example 2 By the same synthesis method as in Example 1, GA
A polymer containing about 25 mol% of a component (hereinafter referred to as HGA)
-25), and the same operation as in Example 1 was carried out except that the filter was coated in the same manner as in Example 1. The average introduction density of the hydrophilic basic groups on the surface of the filter material was 7.5 μeq / m ² , and the microaggregate removal rate was 87%. As in Example 1, there was no adsorption of red blood cells to the filter material, and no clogging of the filter.

[0049]

Example 3 By the same synthesis method as in Example 1, GA
(Hereinafter referred to as HGA)
-40), and the same operation as in Example 1 was carried out except that the filter was coated in the same manner as in Example 1. The average introduction density of the hydrophilic basic groups on the filter material surface was 10.5 μeq / m ² , and the removal rate of microaggregates was 98%. As in Example 1, there was no adsorption of red blood cells to the filter material, and no clogging of the filter.

[0050]

Example 4 By the same synthesis method as in Example 1, GA
A polymer containing about 70 mol% of a component (hereinafter, HGA
-70), and the same operation as in Example 1 was carried out except that the filter was coated in the same manner as in Example 1. The average introduction density of the hydrophilic basic groups on the surface of the filter material was 15.7 μeq / m ² , and the microaggregate removal rate was 97%. As in Example 1, there was no adsorption of red blood cells to the filter material, and no clogging of the filter.

[0051]

Comparative Example 1 By the same polymerization method as in Example 1, N,
N-diethylaminoethyl methacrylate (hereinafter referred to as DE
) And a polymer consisting of HEMA was synthesized. The DE content in the obtained polymer was about 5 mol% (hereinafter, this polymer is referred to as HDE-5), and the same as in Example 1 except that this polymer was coated on a filter in the same manner as in Example 1. The operation was performed. The average introduction density of basic groups (diethylamino groups) on the filter material surface was 1.6 μeq / m ² , and the microaggregate removal rate was 43 μg / m ^2.
%Met. Adsorption of red blood cells to the filter material is low,
There was no filter clogging, but the microaggregate removal rate was low.

[0052]

Comparative Example 2 The same polymerization method as in Comparative Example 1 was used to obtain DE.
(Hereinafter referred to as HDE-25) was obtained, and the same operation as in Example 1 was performed except that the filter was coated in the same manner as in Example 1. The average introduction density of the basic group on the filter material surface was 8.2 μeq / m ² , and the microaggregate removal rate was 46%. After the filter material after blood filtration was washed with physiological saline, it was fixed with 0.2% glutaraldehyde and further freeze-dried. When the filter material after the blood filtration, which had been subjected to such pretreatment, was observed with a scanning electron microscope, it was observed that red blood cells were adsorbed remarkably. Also, the filter was found to be moderately clogged.

[0053]

Comparative Example 3 The same polymerization method as in Comparative Example 1 was used to obtain DE.
(Hereinafter referred to as HDE-40), and the same operation as in Example 1 was performed, except that the polymer was coated on the filter in the same manner as in Example 1. The average introduction density of the basic group on the filter material surface was 12.7 μeq / m ² , and the microaggregate removal rate was 41%. In addition, it was observed that red blood cells were remarkably adsorbed on the filter material after blood filtration.
The clogging of the filter was remarkable.

[0054]

COMPARATIVE EXAMPLE 4 By the same polymerization method as in Example 1, N,
N-diethylaminomethyl methacrylate (hereinafter referred to as DM
) And a polymer consisting of HEMA was synthesized. The DM content in the obtained polymer was about 3 mol% (hereinafter, this polymer is referred to as HDM-3), and the same as in Example 1 except that this polymer was coated on a filter in the same manner as in Example 1. The operation was performed. The average introduction density of basic groups (dimethylamino groups) on the surface of the filter material was 1.1 μeq / m ² , and the microaggregate removal rate was 40%.
%Met. Adsorption of red blood cells to the filter material is low,
There was no filter clogging, but the microaggregate removal rate was low.

[0055]

Comparative Example 5 DM was prepared by the same polymerization method as in Comparative Example 1.
(Hereinafter, this polymer is referred to as HDM-30), and the same operation as in Example 1 was carried out except that the filter was coated in the same manner as in Example 1. The average introduction density of the basic group on the surface of the filter material was 8.9 μeq / m ² , and the microaggregate removal rate was 52%. After the filter material after blood filtration was washed with physiological saline, it was fixed with 0.2% glutaraldehyde and further freeze-dried. When the filter material after the blood filtration, which had been subjected to such pretreatment, was observed with a scanning electron microscope, it was observed that red blood cells were adsorbed remarkably. Also, the filter was moderately clogged.

[0056]

Comparative Example 6 By the same polymerization method as in Example 1, N,
A polymer composed of N-diethylamino-2-hydroxypropyl methacrylate (hereinafter, referred to as DP) and HEMA was synthesized. The DP content in the obtained polymer is about 4
0 mol% (hereinafter, this polymer is referred to as HDP-40
The operation was performed in the same manner as in Example 1 except that this polymer was coated in the same manner as in Example 1. A hydrophilic basic group having no hydrophilic portion at the terminal was introduced into the surface of the filter material at an average introduction density of 11.7 μeq / m ² . The microaggregate removal rate was 51%. When the filter material after filtering the blood was observed with a scanning electron microscope, it was observed that red blood cells were adsorbed remarkably, and the filter was moderately clogged.

[0057]

Example 5 N-methyl-N-hydroxyethylamino
-2-hydroxypropyl methacrylate (GM)
In the same manner as in the synthesis of GA in Example 1, glycidyl methacrylate and N-methyl-N-hydroxyethylamine were converted to N-methyl-N-hydroxyethylamino-2-hydroxypropyl methacrylate (hereinafter referred to as GM).
Was synthesized).

Synthesis of Coating Polymer A polymer comprising GM and HEMA was synthesized by the same polymerization method as in Example 1. G in the obtained polymer
The M content was about 25 mol% (hereinafter, this polymer is referred to as HGMA-25).

Filtration of blood containing red blood cells The same operation as in Example 1 was carried out except that the polymer was coated on a filter in the same manner as in Example 1.
Hydrophilic basic groups (N-methyl-N
-Hydroxyethylamino group) has an average introduction density of 7.5.
μeq / m ² , and the microaggregate removal rate was 85%. As in Example 1, there was no adsorption of red blood cells to the filter material, and no clogging of the filter.

[0060]

Example 6 By the same polymerization method as in Example 1, GA
And a polymer consisting of HEMA and methyl methacrylate (hereinafter referred to as MMA) was synthesized. According to acid-base titration, nuclear magnetic resonance spectrum (NMR) and elemental analysis, the obtained polymer was found to have about 20 mol% GA, HEMA and M
Each of the polymers contained about 40 mol% of MA (hereinafter, this polymer is referred to as HMGA-20). The same operation as in Example 1 was performed except that the polymer was coated on a filter in the same manner as in Example 1. The average introduction density of hydrophilic basic groups on the filter material surface is 6.7 μeq /
m ² , and the microaggregate removal rate was 86%. As in Example 1, there was no adsorption of red blood cells to the filter material,
There was no clogging of the filter.

[0061]

Example 7 Having an ethylene oxide chain and an amino group
Synthesis of polymerizable monomer (EA) Trioxyethyl monomethyl ether was added at 0.1 mol /
Thionyl chloride was gradually added to the pyridine solution adjusted to have a concentration of L while cooling so as to have a concentration of 0.13 mol / L, followed by stirring at room temperature for about 1 hour. After cooling, water and diluted sulfuric acid were added to decompose excess thionyl chloride, and the reaction product was extracted with chloroform. The extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and then distilled under reduced pressure to synthesize a compound having a terminal hydroxyl group chlorinated. N-methylallylamine (0.1mo
l) was dissolved in 50 mL of absolute ethanol, and after cooling, the chlorinated compound (0.1 mol) was added, and 3
By stirring for 0 minutes, a polymerizable monomer (hereinafter referred to as EA) having an ethylene oxide chain as a hydrophilic portion and an amino group as a basic portion was synthesized.

Synthesis of Coating Polymer A polymer comprising EA and HEMA was synthesized by the same polymerization method as in Example 1. EA in the obtained polymer
The content was about 25 mol% (hereinafter, this polymer is referred to as HEA-25).

Filtration of Red Blood Cell-Containing Blood The same operation as in Example 1 was carried out except that this polymer was coated on a filter in the same manner as in Example 1.
The average introduction density of hydrophilic basic groups on the surface of the filter material was 6.5 μeq / m ² , and the removal rate of microaggregates was 83%.
Met. As in Example 1, there was no adsorption of red blood cells to the filter material, and the filter was not clogged.

[0064]

Example 8 A polyester nonwoven fabric (5 g) having an average fiber diameter of 13.1 μm was immersed in 6 mL of a 10% aqueous solution of tertiary butyl alcohol containing methacrylic acid (300 mL). By irradiating this sample solution with γ-rays of about 1 kGy, methacrylic acid was graft-polymerized on the surface of the nonwoven fabric.
The nonwoven fabric irradiated with γ-rays was washed by shaking at room temperature with methanol for 10 minutes, and further washed by shaking with warm water at 40 ° C. for 2 hours. After vacuum drying at 40 ° C. for 16 hours, the nonwoven fabric obtained by graft polymerization was immersed in a chloroform solution containing triethanolamine at a concentration of 0.02 mol / L, sulfuric acid was added, and the mixture was heated under reflux for 6 hours. By such an operation, esterification is caused by the carboxyl group on the surface of the nonwoven fabric and the hydroxyl group of triethanolamine, and a fine aggregate removal filter material having a hydrophilic basic group (bis (hydroxyethyl) amino group) on the surface is obtained. Produced. The density of introduction of hydrophilic basic groups on the filter material surface is 6.6.
μeq / m ² . The obtained filter material was placed in a container having an effective filtration area of 67 mm × 67 mm and a thickness of 3.0 mm.
A filter device packed so as to have a packing density of 0.27 g / cm ^{3 in} mm was prepared. When the concentrated red blood cell preparation was filtered using this filter device in the same manner as in Example 1, the microaggregate removal rate was 94%. As in Example 1, there was no adsorption of red blood cells to the filter material, and no clogging of the filter.

[0065]

Comparative Example 7 A polyester nonwoven fabric having an average fiber diameter of 1.8 μm was placed in a container having a blood inlet and outlet and an effective filtration area of 67 mm × 67 mm and a packing density of about 0.2 mm.
3 g / cm ³ and a thickness of 2.1 mm were filled.
HGA-25 polymer was coated on the filter in the same manner as in Example 1. This filter material is WO9
9/11304, which is a leukocyte removal filter material having extremely excellent leukocyte removal ability. Using this apparatus, the operation of the concentrated erythrocyte preparation was filtered in the same manner as in Example 1. The average introduction density of hydrophilic basic groups on the surface of the filter material was 7.7 μeq / m ² . As soon as the concentrated erythrocyte preparation began to be filtered, the flow rate decreased and blood stopped flowing. When the uppermost layer of the polyester nonwoven fabric was observed with a scanning electron microscope by performing the same operation as in Comparative Example 2, adsorption of red blood cells was not observed, but microaggregates were captured and clogged. Was observed.

[0066]

Comparative Example 8 A polyester nonwoven fabric having an average fiber diameter of 58.4 μm was packed into a container having a blood inlet and outlet and an effective filtration cross-sectional area of 67 mm × 67 mm and a packing density of about 0.3 mm.
The filling was performed so as to have a thickness of 28 g / cm ³ and a thickness of 2.0 mm. The filter was coated with the HGA-25 polymer in the same manner as in Example 1, and the operation was performed in the same manner as in Example 1 to filter the concentrated red blood cell preparation. The average introduction density of hydrophilic basic groups on the surface of the filter material was 7.3 μeq / m ² . The microaggregate removal rate was 43%. There was no red blood cell adsorption to the filter material and no clogging of the filter, but the microaggregate removal rate was low.

Table 1 summarizes the results of Examples 1 to 8 and Comparative Examples 1 to 8 described above.

[Table 1]

From the above results, it was found that the microaggregates of Examples 1 to 8 of the present invention having a hydrophilic basic group containing a nonionic hydrophilic portion and a basic portion on at least the surface of the fibrous porous substrate. In the substance removal filter, the microaggregate removal rate was excellent, and there was no red blood cell adhesion and clogging, whereas Comparative Examples 1 to 2 having a nonionic hydrophilic group and a basic group independently.
It was found that the filter of No. 5 had a low microaggregate removal rate and caused red blood cell adhesion or clogging. In Comparative Example 6, which has a nonionic hydrophilic basic group but does not have a hydrophilic portion at the end, it was found that the microaggregate removal rate was low, erythrocyte adhesion was remarkable, and clogging occurred. Was. Further, the fiber diameter of the fibrous porous substrate of the present invention even if it has a hydrophilic basic group containing a nonionic hydrophilic portion and a basic portion on at least the surface of the fibrous porous substrate. It was found that the filters of Comparative Examples 7 and 8, which were out of the range, had problems such as clogging and a low microaggregate removal rate.

[0069]

Example 9 A nonwoven fabric made of polyester having an average fiber diameter of 32.2 μm and having an average fiber diameter of 32.2 μm was prepared by a spunbond method in a container having an inlet and an outlet for blood and having an effective filtration area of 67 mm × 67 mm. A polyester nonwoven fabric having an average fiber diameter of 13.1 μm was disposed at a thickness of 0.7 mm in the lower layer, and the lower layer was filled at a thickness of 1.0 mm, and the packing density was 0.28 g / cm ³ . . HGA-2
Five polymers were coated on the filter in the same manner as in Example 1. A filter material was taken out of the above filter, and was placed in a container having an inlet and an outlet for blood and having an effective filtration cross-sectional area of 67 mm x 67 mm. 28 g / cm ^3, and the lower layer was filled with a polyester nonwoven fabric having an average fiber diameter of 1.7 μm so as to have a thickness of 4.0 mm and a packing density of 0.23 g / cm ³ . .
A concentrated erythrocyte preparation was prepared in the same manner as in Example 1 and stored at 4 ° C. for 16 days. 325 g of this concentrated red blood cell preparation
Was allowed to reach a room temperature of 25 ° C., and filtered at a drop of 1.0 m using the above filter. After the filter was filled with blood and filtration was started, filtration was performed until no blood remained in the blood bag, and the filtered blood was collected. The filtration time at this time was from the time when blood began to flow out of the outlet of the filter to the time when the collected liquid amount reached 250 g. The time required to filter blood from 0 g to 50 g (t (1))
And the time required to filter the blood from 200 g to 250 g (t (2)) was measured, and the flow rate maintenance rate was measured from the following equation. Flow rate maintenance rate (%) = {t (1) / t (2)} × 10
The time required for zero filtration was 10.8 minutes, and the flow rate maintenance rate was 91%.
Met. When the uppermost layer of the nonwoven fabric made of polyester having an average fiber diameter of 1.7 μm among the filter materials after blood filtration was observed using a scanning electron microscope in the same operation as in Comparative Example 2, almost no microaggregates were found. Not observed.

[0070]

[Comparative Example 9] In the same manner as in Example 9, HD was added to the filter.
The operation was performed in the same manner as in Example 9 except that the filter material was taken out and used after coating with E-5. The average introduction density of hydrophilic basic groups on the filter material surface is 1.7 μe
q / m ² . The time required for filtration was 14.8 minutes, and the flow rate maintenance rate was 68%. When the uppermost layer of the nonwoven fabric made of polyester having an average fiber diameter of 1.7 μm among the filter materials after blood filtration was observed with a scanning electron microscope in the same operation as in Comparative Example 2, microaggregates were captured. The situation was observed. It is presumed that the uppermost layer of the polyester nonwoven fabric having an average fiber diameter of 1.7 μm was clogged with microaggregates, resulting in an increase in filtration time and a decrease in flow rate retention.

According to the comparison between Example 9 and Comparative Example 8, the fibrous porous base material of the present invention having a hydrophilic basic group containing a nonionic hydrophilic portion and a basic portion on at least the surface of the fibrous porous substrate. When a microaggregate removal filter was used (Example 9), the flow rate could be maintained during hemofiltration.
Comparative Example 9 having a nonionic hydrophilic group and a basic group independently
It was found that in the filter of No. 1, the filtration time was prolonged and the flow rate maintenance rate was lowered due to clogging.

[0072]

As described above, according to the present invention, a hydrophilic basic material containing a nonionic hydrophilic portion and a basic portion on at least the surface of a fibrous porous substrate having an average fiber diameter of 8 μm or more and less than 50 μm. By using a filter material having a group, the microaggregate removal rate is extremely high, the blood product processing speed can be maintained at a high state, the adsorption of red blood cells to the filter is suppressed, and the loss of blood components in the filter is reduced. The effect that it can be reduced as much as possible was achieved.

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C077 AA11 BB02 CC06 KK10 KK13 MM07 MM08 NN01 NN02 PP02 PP07 4D019 AA03 BA12 BA13 BA20 BB02 BB03 BC13 BD01 DA02 DA03

Claims (12)

[Claims] 1. A filter material for removing microaggregates from erythrocyte-containing blood containing microaggregates, said filter material comprising a fibrous porous body having an average fiber diameter of 8 μm or more and less than 50 μm as a base material. Has a hydrophilic basic group including a nonionic hydrophilic portion and a basic portion on at least the surface thereof, and in the hydrophilic basic group, the hydrophilic portion is closer to the terminal than the basic portion. A micro-aggregate removal filter material, characterized in that it is located in 2. The filter material for removing microaggregates according to claim 1, wherein at least one hydrophilic portion is located at the extreme end of the hydrophilic basic group. 3. The filter material for removing microaggregates according to claim 1, wherein the hydrophilic portion is a hydroxyl group. 4. The filter material for removing microaggregates according to claim 1, wherein the basic moiety is a secondary and / or tertiary amino group. 5. The filter material according to claim 1, wherein the hydrophilic basic group is a hydroxyalkylamino group. 6. The fibrous porous substrate according to claim 1, wherein a monomer containing a hydrophilic basic group and / or a polymer containing a monomer containing a hydrophilic basic group as a component is introduced into the surface of the fibrous porous substrate. The microaggregate removal filter material according to any one of the above. 7. The filter material for removing microaggregates according to claim 6, wherein the polymer containing a monomer containing a hydrophilic basic group as a component is a copolymer with a monomer containing no hydrophilic basic group. 8. The filter material for removing microaggregates according to claim 6, wherein the polymerizable monomer containing a hydrophilic basic group is a (meth) acrylic acid derivative. 9. The density of the hydrophilic basic group per unit surface area of the filter material is 0.1 μeq / m ² or more and 1000 μm.
microaggregates removing filter material according to any one of claims 1 to 8 is less than eq / m ^2. 10. The number of basic parts with respect to the number of hydrophilic parts on the surface of the filter material is 0.01 to 0.5.
The microaggregate removal filter material according to any one of claims 1 to 9, which is: 11. An erythrocyte containing microaggregates from an inlet using at least 1) an inlet, 2) a filter including the filter material for removing microaggregates according to claim 1, and 3) an outlet. A method for removing microaggregates from blood containing erythrocytes containing microaggregates, comprising injecting blood containing blood and collecting the liquid filtered by the filter from an outlet. 12. The method for removing microaggregates from microaggregate-containing red blood cell-containing blood according to claim 11, wherein a leukocyte removal filter material is disposed downstream of the microaggregate removal filter material.