JP7340020B2 - BLOOD PROCESSING FILTER AND BLOOD PRODUCT MANUFACTURING METHOD - Google Patents

Description

The present invention relates to blood processing filters and methods for producing blood products.

In the field of blood transfusion, in addition to the so-called whole blood transfusion, in which blood is collected from a donor and transfused with an anticoagulant added, blood components required by the recipient are separated from the whole blood product. , so-called component transfusion, in which the blood components are transfused, has become common practice. Component transfusions include red blood cell transfusions, platelet transfusions, and plasma transfusions, depending on the type of blood component required by the recipient. There is

Recently, so-called leukocyte-removed transfusion, in which leukocytes contained in blood products are removed before transfusion of blood products, has become popular. This includes relatively minor side effects, such as transfusion-associated headache, nausea, chills, and nonhemolytic febrile reactions, as well as severe side effects, such as alloantigen sensitization, viral infections, and post-transfusion GVHD, which severely affect the recipient. This is because it has become clear that serious side effects are caused mainly by leukocytes that are mixed in blood products used for transfusion. In order to prevent relatively minor side effects such as headache, nausea, chills, and fever, it is said that leukocytes in blood preparations should be removed until the residual rate is 10 ^-1 to 10 ^-2 or less. there is In addition, it is said that it is necessary to remove leukocytes until the survival rate is 10 ⁻⁴ to 10 ⁻⁶ or less in order to prevent alloantigen sensitization and viral infection, which are serious side effects.
Further, in recent years, leukocyte removal therapy using extracorporeal blood circulation has been performed for the treatment of diseases such as rheumatoid arthritis and ulcerative colitis, and high clinical effects have been obtained.

At present, methods for removing leukocytes from blood products can be broadly divided into centrifugal methods in which leukocytes are separated and removed by using a centrifugal separator and utilizing differences in the specific gravity of blood components, and methods for separating and removing leukocytes using a centrifugal separator. There are two types of filtering methods in which leukocytes are removed using a filter element composed of a porous structure having pores. The filter method, in which leukocytes are removed by adhesion or adsorption, is currently most popular because it has advantages such as simple operation and low cost.

In recent years, new demands have been raised for leukocyte-removing filters in the medical field. One of the requirements is to make the filter smaller and lighter in order to reduce the disposal cost of the filter. The reason for this is that after filtering blood, filters represent infectious waste and generally have a disposal cost per weight. By downsizing, medical institutions can further reduce unnecessary costs.

In this case, an effective filter design concept is to increase the effective utilization rate of the filtering material used in the filter. This is because a sufficient amount of leukocytes in the blood can be adsorbed even with a small amount of filtering material by improving the effective utilization rate. As a means for this, when the blood flows into the filter, the blood spreads evenly in the filter by uniformly distributing the filtering material in the direction that spreads perpendicularly to the flow (usually in the plane direction of the filter), resulting in an effective result. The method of improving the utilization rate is often used.

As a specific example, in Patent Document 1, a nonwoven fabric, which is a type of filtering material, is used to improve the homogeneity in the plane direction (improve the texture), thereby increasing the leukocyte removal rate of the filtering material. It is disclosed to improve

In addition, Patent Document 2 discloses a technique that achieves both the effect of improving the leukocyte removal rate and shortening the filtration time by appropriately controlling the blood flow speed (permeation coefficient) in the planar direction and the vertical direction of the filter. It is

International Publication No. 2004/050146 International Publication No. 2005/120600

In the filter material of Patent Document 1, in which the fibers of the nonwoven fabric are uniformly distributed, aggregates contained in blood uniformly clog the surface of the nonwoven fabric. was found to be unsuitable for It was also found that since blood with low viscosity passes through the filter immediately, the residence time in the filter is too short, resulting in a low leukocyte removal rate. In other words, there is a problem that it can only filter specific blood that has an appropriate viscosity and does not contain aggregates of a size that induces clogging as much as possible.

Patent Document 2 does not specifically define the anisotropy of the flow in the plane, so it does not even consider how to control the flow in the plane and make effective use of it. There have been cases in which uneven flow occurs in the plane and the filtration performance cannot be sufficiently exhibited. In other words, due to in-plane flow inhomogeneity, low-viscosity blood only passes through some areas of the filter, and the entire filter is not utilized, resulting in poor filtration performance and poor blood flow. There is a problem that the filter design needs to be changed depending on the properties of the filter.

An object of the present invention is to provide a blood processing filter excellent in leukocyte removal rate and filtration time (filtration rate).

As a result of intensive studies, the present inventor found that the above problems can be solved by adjusting the orientation of the fibers of the nonwoven fabric contained in the filter layer that constitutes the filter medium. The present inventors have also found that the above problem can be solved by providing a predetermined space inside the filter layer that constitutes the filter medium.

That is, the present invention is as follows.
[1]
a container having an inlet and an outlet for blood;
a filter medium disposed within the container between the inlet and the outlet;
A blood processing filter comprising:
the filter medium comprises a filter layer,
the filter layer comprises a non-woven fabric,
The fibers of the nonwoven fabric have an orientation degree X in the X-axis plane direction of the filter layer and an orientation degree Y in the Y-axis plane direction orthogonal to the X-axis plane direction,
The maximum value of the ratio of the orientation degree X to the orientation degree Y (orientation degree X/orientation degree Y) is 1.2 or more.
Said blood processing filter.
[2]
The blood processing filter according to [1], wherein the maximum value of orientation degree X/orientation degree Y is 1.4 or more.
[3]
The ratio (Ac /Am) is 1.2 or more, the blood processing filter according to [1] or [2].
[4]
The blood processing filter according to [3], wherein Ac/Am is 1.4 or more.
[5]
The ratio (Am The blood processing filter according to [1] or [2], wherein the filter layer is arranged such that /Ac) is 1.2 or more.
[6]
The blood processing filter according to [5], wherein Am/Ac is 1.4 or more.
[7]
The blood treatment filter according to any one of [1] to [6], wherein the nonwoven fabric is a polyester nonwoven fabric.
[8]
a container having an inlet and an outlet for blood;
a filter medium disposed within the container between the inlet and the outlet;
A blood processing filter comprising:
the filter medium comprises one or more filter layers;
The filter layer has a space with a maximum length of 50 μm or more in the planar direction and a maximum length of 15 μm or more in the thickness direction in a cross section in the thickness direction.
Said blood processing filter.
[9]
The blood processing filter according to [8], wherein the filter layer has a filling factor of 0.09 to 0.26.
[10]
The blood processing filter according to [8] or [9], wherein the difference between the minimum in-plane porosity in the thickness direction and the maximum in-plane porosity in the thickness direction of the filter layer is 0.08 to 0.28.
[11]
The blood processing filter according to [10], wherein the minimum in-plane porosity in the thickness direction is 0.72 to 0.85, and the maximum in-plane porosity in the thickness direction is 0.85 to 1.00.
[12]
The blood processing filter according to any one of [8] to [11], wherein the filter layer has a specific surface area of 0.50 to 1.50 m ² /g.
[13]
The blood processing filter according to any one of [8] to [12], wherein the filter layer has a critical wetting surface tension of 70 to 100 dyn/cm.
[14]
A method for producing a blood product, comprising the step of allowing blood containing leukocytes to pass through the blood processing filter according to any one of [1] to [13].

ADVANTAGE OF THE INVENTION According to this invention, the blood processing filter excellent in the leukocyte removal rate and filtration time (filtration rate) can be provided.

1 is a schematic diagram of a blood processing filter that is an embodiment of the present invention; FIG. 2 is a cross-sectional view of the blood processing filter of FIG. 1; FIG. 1 is a schematic diagram of a blood processing filter that is an embodiment of the present invention; FIG. FIG. 4 is a schematic front view of the plane of the blood processing filter of FIG. 3 ; FIG. 4 is a diagram showing a method for adjusting Ac:Am; FIG. 4 is a diagram showing a method for adjusting Ac:Am; A method for testing leukocyte removal performance is shown. 1 shows a cross section in the thickness direction of the filter layer of Example A1 (a cut surface cut in the thickness direction). 8B is an enlarged view of the cross-section of FIG. 8A; FIG. 2 shows the in-plane porosity in the thickness direction of the filter layer of Example A1. FIG. 10 shows the in-plane porosity in the thickness direction of the filter layer of Example A12. FIG. FIG. 3 shows the in-plane porosity in the thickness direction of the filter layer of Comparative Example A1. FIG. FIG. 10 shows the in-plane porosity in the thickness direction of the filter layer of Comparative Example A2. FIG. An example of the manufacturing method of a nonwoven fabric is shown.

EMBODIMENT OF THE INVENTION Hereinafter, the form (henceforth "this embodiment") for implementing this invention is demonstrated in detail. It should be noted that the present invention is not limited to the following embodiments, and various modifications can be made within the scope of the gist of the present invention.

Hereinafter, unless otherwise specified, the term "blood" includes blood and blood component-containing liquids. Blood component-containing liquids include, for example, blood products. Examples of blood products include whole blood products, red blood cell products, platelet products, plasma products and the like.

<First blood processing filter>
One embodiment of the present invention comprises a container having a blood inlet and an outlet;
a filter medium disposed within the container between the inlet and the outlet;
A blood processing filter comprising:
The filter medium includes a filter layer (hereinafter also referred to as "first filter layer"),
the filter layer comprises a non-woven fabric,
The fibers of the nonwoven fabric have an orientation degree X in the X-axis plane direction of the filter layer and an orientation degree Y in the Y-axis plane direction orthogonal to the X-axis plane direction,
The maximum value of the ratio of the orientation degree X to the orientation degree Y (orientation degree X/orientation degree Y) is 1.2 or more.
It relates to the blood processing filter.
By adjusting the orientation of the fibers of the nonwoven fabric contained in the filter layer, excellent leukocyte removal rate and excellent filtration time (filtration rate) can be exhibited.

FIG. 1 is a schematic diagram of one embodiment of a blood processing filter (leukocyte removal filter), and FIG. 2 is a cross-sectional view taken along line II-II of FIG.
As shown in FIGS. 1 and 2, the blood processing filter 10 has a flat container 1 and a substantially dry filter medium 5 housed therein. A container 1 containing filter media 5 is composed of two elements, an inlet-side container material having an inlet portion 3 and an outlet-side container material having an outlet portion 4 . The space in the flat container 1 is partitioned by the filter medium 5 into a space 7 on the side of the inlet and a space 8 on the side of the outlet.
In this blood processing filter 1, the inlet-side container material and the outlet-side container material are arranged with the filter medium 5 interposed therebetween, and the two container materials hold the filter medium 5 at a grip part provided at a part thereof. A structure is adopted in which the outer edge portion 9 is pinched and gripped.

Further, in one embodiment, the filter medium and the container may be joined by welding or the like so that the filter medium is gripped by the container.

[container]
Examples of materials for the container include hard resins and flexible resins.
Examples of hard resins include phenolic resins, acrylic resins, epoxy resins, formaldehyde resins, urea resins, silicon resins, ABS resins, nylons, polyurethanes, polycarbonates, vinyl chlorides, polyethylenes, polypropylenes, polyesters, and styrene-butadiene copolymers. etc.
The flexible resin preferably has thermal and electrical properties similar to those of the filter layer. Flexible resins include, for example, soft polyvinyl chloride, polyurethane, ethylene-vinyl acetate copolymer, polyolefins such as polyethylene and polypropylene, hydrogenated styrene-butadiene-styrene copolymer, styrene-isoprene-styrene Examples include thermoplastic elastomers such as copolymers or hydrogenated products thereof, and mixtures of thermoplastic elastomers with softeners such as polyolefins and ethylene-ethyl acrylate. Flexible resins, preferably soft polyvinyl chloride, polyurethane, ethylene-vinyl acetate copolymer, polyolefin, and thermoplastic elastomers containing these as main components, more preferably soft polyvinyl chloride and polyolefin .

For example, when the filter medium is flat, the shape of the container can be polygonal such as quadrangular or hexagonal, or flat such as circular or elliptical, depending on the shape (for example, FIG. 1 and FIG. 1). 2). Moreover, when the filter medium is cylindrical, the container is preferably cylindrical as well.

[Filter medium]
(First filter layer)
The filter medium includes one or more first filter layers. When the filter medium includes multiple first filter layers, each of the multiple first filter layers may be the same or different.

Preferably, the first filter layer comprises a nonwoven fabric. The nonwoven fabric is preferably laminated. Materials for the non-woven fabric are not particularly limited, but examples thereof include polyester (eg, polyethylene terephthalate (PET) and polybutylene terephthalate (PBT)), polyamide, polyacrylonitrile, polymethyl methacrylate, polyethylene, and polypropylene. By using such materials, denaturation of blood can be prevented. From the viewpoint of affinity with blood products and wettability with blood, the material of the nonwoven fabric is preferably polyester, more preferably PET or PBT. The nonwoven fabric may be made of only one type of material, or may be made of multiple types of materials.

The nonwoven fabric contained in the first filter layer may have a coat layer on its surface. In addition, in this specification, the nonwoven fabric which does not have a coat layer is also called a "fiber base material." By appropriately selecting the material of the coat layer, the ζ potential of the surface can be easily set to 0 mV or higher.

The coat layer preferably contains, for example, a copolymer having monomer units having a nonionic hydrophilic group and monomer units having a basic nitrogen-containing functional group. By using a copolymer having a basic nitrogen-containing functional group, the surface of the nonwoven fabric can be positively charged by coating treatment, and the affinity with leukocytes can be improved.

Examples of monomer units having a nonionic hydrophilic group include monomer units derived from 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, vinyl alcohol, (meth)acrylamide, N-vinylpyrrolidone, and the like. is mentioned. From the viewpoints of availability, ease of handling during polymerization, performance when blood is shed, etc., the monomer unit having a nonionic hydrophilic group is preferably a monomer derived from 2-hydroxyethyl (meth)acrylate. Units. Monomer units derived from vinyl alcohol are usually produced by hydrolysis after polymerization of vinyl acetate.

Monomer units having a basic nitrogen-containing functional group include, for example, diethylaminoethyl (meth)acrylate, dimethylaminoethyl (meth)acrylate, dimethylaminopropyl (meth)acrylate, 3-dimethylamino-2-hydroxypropyl (meth) (meth)acrylic acid derivatives such as acrylates; styrene derivatives such as p-dimethylaminomethylstyrene and p-diethylaminoethylstyrene; nitrogen-containing aromatic compounds such as 2-vinylpyridine, 4-vinylpyridine and 4-vinylimidazole; vinyl derivatives; and monomer units derived from derivatives obtained by converting the above vinyl compounds into quaternary ammonium salts with alkyl halides or the like. From the viewpoints of availability, ease of handling during polymerization, performance when blood is shed, etc., the monomer unit having a basic nitrogen-containing functional group is preferably diethylaminoethyl (meth)acrylate and dimethylaminoethyl (meth)acrylate. It is a monomer unit derived from (meth)acrylate.

The weight of the coat layer is preferably about 0.1 to 40.0 mg when the total weight of the fiber base material and the coat layer is 1 g. By setting the coating amount within such a range, uniform coating is facilitated, and problems such as clogging of blood cells and uneven flow of blood that deteriorate filtration performance can be avoided. .

The mass of the coat layer can be calculated, for example, by the following procedure. The nonwoven fabric (fiber base material) before supporting the coat layer is dried for 1 hour in a dryer set at 60 ° C., then left in a desiccator for 1 hour or more, and then the mass (Ag) is measured. The nonwoven fabric carrying the coat layer is similarly dried in a dryer at 60° C. for 1 hour, left in a desiccator for 1 hour or more, and then weighed (Bg). The mass of the coat layer is calculated by the following formula.
Weight (mg/g) of coat layer with respect to total (1 g) of nonwoven fabric (fiber base material) and coat layer
= (BA) × 1000/B

The method of forming the coating layer on the fiber base material is not particularly limited. For example, the fiber base material is immersed in a coating liquid containing a monomer and/or polymer (copolymer) and, if necessary, a solvent or the like, and then the coating liquid is applied as appropriate. Examples include a method of removing (dip method) and a method of coating by bringing the fiber base material into contact with a roll immersed in the coating liquid (transfer method).

The nonwoven fabric contained in the first filter layer preferably has basic nitrogen-containing functional groups on its peripheral surface portion.
By peripheral surface portion of the nonwoven is meant all portions of the nonwoven that are exposed to the outside world. That is, if the nonwoven fabric has a coat layer, the peripheral surface portion is the surface portion of the coat layer. If the nonwoven does not have a coating layer, the peripheral surface portion means the surface portion of the fibrous substrate.
The peripheral surface portion of the nonwoven may further have nonionic hydrophilic groups.

When basic nitrogen-containing functional groups are present on the peripheral surface portion of the nonwoven fabric, the affinity between the nonwoven fabric and leukocytes in blood increases, and the leukocyte removal performance can be improved.
In addition, when non-ionic hydrophilic groups are present in the peripheral surface portion of the nonwoven fabric, the wettability of the nonwoven fabric surface to blood increases, and the effective filtration area (area actually used for filtration) of the nonwoven fabric increases, resulting in filtration. Both effects of reduction of time and improvement of leukocyte and the like removal performance can be obtained.

As a method for providing a non-ionic hydrophilic group or a basic nitrogen-containing functional group on the peripheral surface portion of the nonwoven fabric, for example, in the case of a non-woven fabric having a coat layer, a non-ionic hydrophilic group or a basic nitrogen-containing functional group is added. A method of coating a non-woven fabric with a coating material containing a monomer and / or polymer containing a non-woven fabric, in the case of a non-woven fabric having no coat layer, a monomer and / or polymer containing a nonionic hydrophilic group or a basic nitrogen-containing functional group A method of spinning using a fiber material containing the fiber, and the like.

The ratio of the amount of basic nitrogen-containing functional groups to the total amount of nonionic hydrophilic groups and basic nitrogen-containing functional groups in the peripheral surface portion of the nonwoven fabric is preferably 0.2 to 50.0 mol percent. , more preferably 0.25 to 10 mol percent, more preferably 1 to 5 mol percent, and most preferably 2 to 4 mol percent. The content of basic nitrogen-containing functional groups and nonionic hydrophilic groups can be measured by analysis using NMR, IR, TOF-SIMS, or the like. By defining the ratio of the basic nitrogen-containing functional group and the nonionic hydrophilic group in this way, while ensuring stable wettability with blood and suppressing unnecessary clogging due to blood components such as platelets, white blood cells etc. can be efficiently removed.

Nonionic hydrophilic groups include, for example, alkyl groups, alkoxy groups, carbonyl groups, aldehyde groups, phenyl groups, amide groups, and hydroxyl groups.
Examples of basic nitrogen-containing functional groups include -NH ₂ , -NHR ¹ , -NR ² R ³ , -N ⁺ R ⁴ R ⁵ R ⁶ (R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ is an alkyl group having 1 to 3 carbon atoms).

(degree of orientation)
The fibers of the nonwoven fabric contained in the first filter layer have an orientation degree X in the X-axis plane direction of the first filter layer and an orientation degree Y in the Y-axis plane direction orthogonal to the X-axis plane direction. , the maximum value of the ratio of the degree of orientation X to the degree of orientation Y (degree of orientation X/degree of orientation Y) is 1.2 or more. Hereinafter, the maximum value of orientation degree X/orientation degree Y is also referred to as "maximum orientation degree ratio".

"Orientation degree" indicates the degree of orientation of fibers in a predetermined direction. For example, a high degree of orientation of fibers in the X-axis direction means that the degree of alignment of fibers parallel to the X-axis direction is high.
"X-axis plane direction" is an arbitrary direction in the plane direction of the first filter layer.
“Y-axis plane direction” is a direction perpendicular to the X-axis in the plane direction of the first filter layer.
A "planar direction" is a direction orthogonal to the thickness direction of the first filter layer.
"Maximum value of orientation degree X/orientation degree Y (maximum orientation degree ratio)" means the largest value among the values of orientation degree X/orientation degree Y in all planar directions of the first filter layer. .

The degree of orientation can be calculated from the orientation index. Like the degree of orientation, the orientation index indicates the degree to which fibers are oriented in a predetermined direction, but the orientation index decreases as the degree of orientation increases. For example, the orientation index of the fibers in the X-axis direction is determined based on the cross-sectional area of the fibers on the plane perpendicular to the X-axis direction. When the fibers are arranged parallel to the X-axis direction, the area of the fibers on the plane orthogonal to the X-axis direction is small. That is, the orientation index in the X-axis direction becomes small.

Assuming that the orientation index in the X-axis plane direction is orientation index X, and the orientation index in the Y-axis plane direction perpendicular to the X-axis plane direction is orientation index Y, the degree of orientation X/the degree of orientation Y is the orientation index Y/ It can be represented by an orientation index X.

The orientation index X and orientation index Y of the nonwoven fabric are determined by X-ray CT and image analysis by the following method. The X-ray CT apparatus and image analysis software used are as follows.
X-ray CT device: Nano3DX high-resolution 3D X-ray microscope manufactured by Rigaku Corporation
Image analysis software: ImageJ

A non-woven fabric sample for X-ray CT measurement is cut into 2.5 mm×2.5 mm in-plane, and the X-ray CT measurement is performed without cutting in the thickness direction and keeping the entire thickness. The measurement conditions are as follows.
Pixel resolution: 0.54 μm/pix
Exposure time: 18 seconds/sheet Number of projections: 1500 sheets/180 degrees X-ray tube voltage: 40 kV
X-ray tube current: 30mA
X-ray target: Cu
Measurement point: The central part of the plane where the influence of the cut surface of the edge of the sample does not appear

The coordinate axes of the nonwoven fabric are set such that the X-axis plane direction is the X-axis, the Y-axis plane direction is the Y-axis, and the thickness direction is the Z-axis. The XY plane corresponds to the in-plane of the nonwoven fabric.
From the tomogram image obtained from the X-ray CT measurement, the image is trimmed with a rectangular parallelepiped of X-axis×Y-axis×Z-axis=500 μm×500 μm×thickness. Let this be a three-dimensional image 1 .
The median filter of the image processing method is applied to the three-dimensional image 1 under the condition of a radius of 2 pix, and then the Otsu method of the image processing method is applied to perform area division. The luminance value of the pixel after the area division is set to 0 for air and 255 for the fibers of the non-woven fabric. An image obtained in this manner is referred to as a three-dimensional image 2 .
Pixels with a luminance value of 255 in the three-dimensional image 2 are subjected to segmentation using an image processing method, and fibers with a pixel count of 10000 pixels or less among continuous fibers with a luminance value of 255 are removed as noise. The image obtained in this way is defined as a three-dimensional image 3 by setting the pixel luminance value to 0 for air and 255 for the fibers of the non-woven fabric.
In this three-dimensional image 3, all the pixels on the XY plane are scanned pixel by pixel in the Z direction perpendicular to the XY plane, and the point where the luminance value changes from 0 to 255 and the point where the luminance value changes from 255 to 0 are detected. The total number is determined by image analysis, and the projected area is defined as _AXY . Similarly, let the total number of the YZ plane scanned in the X direction be the projected area _AYZ , and the total number of the ZX plane scanned in the Y direction be the projected area _AZX . From these projected areas, an orientation index X and an orientation index Y are obtained by the following equations.
Orientation index X= _AYZ /( _AXY + _AYZ + _AZX )
Orientation index Y=A _ZX /(A _XY +A _YZ +A _ZX )

Simply put, the orientation index is obtained by calculating the cross-sectional area (projected area) when observing the nonwoven fabric in that direction, and proportionally distributing it so that the sum of the projected areas in each three-dimensional direction becomes 1. be done. That is, the orientation index in each direction is a number from 0 to 1, and the stronger the orientation in that direction, the smaller the orientation index. In other words, a completely isotropic nonwoven fabric would have orientation indices of 0.33 in the X, Y, and Z directions.

The maximum value of orientation degree X/orientation degree Y (maximum orientation degree ratio) is 1.2 or more, preferably 1.3 to 2.0, more preferably 1.4 to 1.8. When the filter medium includes a plurality of first filter layers, the maximum orientation ratio of the nonwoven fabric contained in at least one first filter layer may be 1.2 or more, but the nonwoven fabric contained in all the first filter layers The maximum orientation ratio is preferably 1.2 or more. By including at least one first filter layer having a nonwoven fabric with a maximum orientation ratio of 1.2 or more, it can be used for high-viscosity blood containing aggregates, low-viscosity blood, or both. Even for intermediate blood, the first filter layer can be effectively used and/or optimized by intentionally guiding the blood flow path in the plane of the first filter layer according to the properties of the blood. A channel can be formed. As a result, blood flowability and leukocyte removal ability can be improved. When the maximum orientation ratio is 2.0 or less, the inductivity of blood in the plane of the first filter layer can be prevented from becoming too strong, so that the flowability and leukocyte removal performance tend to be improved.

In the blood treatment filter according to one embodiment, the degree of orientation (Ac) of the fibers of the nonwoven fabric in the planar direction of the first filter layer, which is perpendicular to the filtration direction, in the planar direction of the first filter layer, which is parallel to the filtration direction It is preferable that the first filter layer is arranged such that the ratio (Ac/Am) to the orientation degree (Am) of the fibers of the nonwoven fabric is 1.2 or more. Ac/Am is more preferably 1.3 to 2.0, still more preferably 1.4 to 1.8.

By "filtration direction" is meant the direction in which blood flows within the blood processing filter, corresponding to the direction from the inlet to the outlet of the container.
"The plane direction of the first filter layer perpendicular to the filtration direction" means, for example, as shown in FIGS. means
"The plane direction of the first filter layer parallel to the filtration direction" means, for example, as shown in FIGS. means

When treating blood from which leukocytes are difficult to remove because of its low viscosity, the flow velocity increases, and when Ac/Am is 1.2 or more, the permeation velocity of the blood into the first filter layer becomes slow, Since the retention time of blood in one filter layer increases, the ability to remove leukocytes can be improved.

In the blood processing filter according to one embodiment, the degree of orientation (Am) of the fibers of the nonwoven fabric in the plane direction of the first filter layer parallel to the filtration direction is It is preferable that the first filter layer is arranged such that the ratio (Am/Ac) to the orientation degree (Ac) of the fibers of the nonwoven fabric is 1.2 or more. Am/Ac is more preferably 1.3 to 2.0, still more preferably 1.4 to 1.8.

When treating blood that has a high viscosity and slows the flow rate and takes a long time to filter, if Am/Ac is 1.2 or more, the permeation rate of blood to the first filter layer increases, and the time to filter is increased. can be shortened.

Ac/Am or Am/Ac can be adjusted accordingly by changing the orientation of the first filter layer. Further, for example, as shown in FIG. 5, by changing the orientation of the nonwoven fabric having a predetermined maximum orientation ratio and cutting the nonwoven fabric at a predetermined rotation angle, the first filter layer having a predetermined Ac/Am or Am/Ac ratio can be obtained. can be created. A line vector can be used to easily confirm the ratio of Ac and Am when the orientation of a nonwoven fabric with a known maximum orientation ratio is arbitrarily changed.

Further, as shown in FIG. 6, by changing the orientation of the nonwoven fabric having the maximum orientation ratio of 1.2 and cutting it, it is possible to satisfy Am≈Ac. In this case, at first glance, it appears to have the same performance as a filter using a nonwoven fabric with a maximum orientation ratio of 1.0, but in reality, the fibers are oriented diagonally in the filter, which induces blood. It is possible to secure a certain retention time in the filter while maintaining the This allows for blood of moderate viscosity and some aggregate content, with normal flow and leukapheresis.
Supplementally, the in-plane permeability coefficient (Ky) of Patent Document 2 is a concept similar to Ac or Am in this specification, but Ky is a composite filter medium characteristic derived from the fluidity of the liquid in the planar direction. and cannot be directly subdivided into numerical values for Ac and Am.

(Filling rate)
The first filter layer preferably has a filling factor of 0.04 to 0.40, more preferably 0.06 to 0.30, even more preferably 0.08 to 0.22. It has a fill factor.

When the filling rate of the first filter layer is 0.40 or less, blood cell clogging tends to be reduced and the processing speed tends to be improved. In addition, when the filling rate is 0.04 or more, the number of times of contact with leukocytes tends to increase and the trapping rate of leukocytes tends to improve, and the mechanical strength of the nonwoven fabric tends to improve.

The packing rate of the first filter layer is measured by the following method. The surface area, thickness, and mass of the first filter layer cut to arbitrary dimensions, and the specific gravity of the fiber material constituting the nonwoven fabric of the first filter layer are measured and calculated by the following formula (10).
Filling rate = [mass (g) of the first filter layer ÷ {area in the plane direction of the first filter layer (cm ² ) × thickness of the first filter layer (cm)}] ÷ constituting the nonwoven fabric of the first filter layer Specific gravity of fiber material (g/cm ³ ) (10)

(formation index)
The first filter layer preferably has a formation index corresponding to a thickness of 0.5 mm of 15 or more and 70 or less. When the formation index is 70 or less, the structure in the thickness direction of the first filter layer is uniform with respect to the filtration surface direction, blood flows evenly through the first filter layer, and the ability to remove leukocytes and the like is improved. Processing speed tends to improve. On the contrary, when the formation index is 15 or more, clogging is less likely to occur due to a decrease in liquid permeation resistance, and the processing speed is improved. The formation index is more preferably 15 or more and 65 or less, still more preferably 15 or more and 60 or less, particularly preferably 15 or more and 50 or less, and most preferably 15 or more and 40 or less.

The formation index is obtained by applying light from below the nonwoven fabric, detecting the transmitted light with a charge-coupled device camera (hereinafter abbreviated as a CCD camera), and measuring the absorbance of the porous body (nonwoven fabric) detected by each pixel of the CCD camera. It is a value obtained by multiplying the coefficient of variation (%) by 10.

The formation index can be measured, for example, with a formation tester FMT-MIII (manufactured by Nomura Shoji Co., Ltd., 2002, S/N: 130). The basic settings of the tester are not changed from the factory shipment, and the total number of pixels of the CCD camera is, for example, about 3400, so that the measurement can be performed. Specifically, the measurement size should be 7 cm × 3 cm (1 pixel size = 0.78 mm × 0.78 mm) so that the total number of pixels is about 3400. The measurement size may be changed so that the number of pixels equals 3400.

Since the formation index is greatly affected by the thickness of the nonwoven fabric, the formation index corresponding to a thickness of 0.5 mm is calculated by the following method.
First, three sheets of nonwoven fabric having a thickness of 0.5 mm or less are prepared, and the formation index and thickness of each sheet are measured. The thickness of the non-woven fabric is the average value when the thickness is measured at arbitrary four points with a measuring pressure of 0.4 N using a constant pressure thickness meter (eg, model FFA-12 manufactured by OZAKI). Next, two of the three measured nonwoven fabrics are stacked so that the thickness is 0.5 mm or more, and the texture index and thickness of the two nonwoven fabrics in the stacked state are measured. After completing the measurement of the formation index for all three combinations, a linear regression equation for the thickness and the formation index is determined, and the formation index corresponding to a thickness of 0.5 mm is obtained from the formula.

If the thickness of the two nonwoven fabrics does not reach 0.5 mm, multiple nonwoven fabrics are layered so that the thickness of the layer is 0.5 mm or more, and the formation index is measured. The formation index may be measured by reducing the amount of nonwoven fabric so that it becomes 0.5 mm or less. The formation index is measured for all combinations of nonwoven fabrics with a thickness of 0.5 mm or less, and the regression line formula for the thickness and the formation index is obtained, and the formation at a thickness of 0.5 mm is interpolated from the formula. An index can be obtained.

Conversely, when the thickness of one nonwoven fabric is greater than 0.5 mm, three nonwoven fabrics are prepared, two of the three are stacked, and the formation index and thickness are measured. The formation index is measured for all combinations of nonwoven fabrics, a linear regression equation between the thickness and the formation index is obtained, and the formation index at a thickness of 0.5 mm can be obtained from the expression by extrapolation.

Three or more nonwoven fabrics used for the measurement of the formation index are preferably cut out from the same filter layer. Usually, they are substantially homogeneous nonwoven fabrics, that is, nonwoven fabrics having the same physical properties (material, fiber diameter, bulk density, filling rate, etc.). However, when it is not possible to obtain the required number of nonwoven fabrics of substantially the same quality from the same filter layer, nonwoven fabrics of the same kind of filter layers may be combined for measurement.

(Specific surface area)
The specific surface area of the first filter layer is preferably 0.8 m ² /g or more and 3.2 m ² /g or less. When the specific surface area is 3.2 m ² /g or less, adsorption of useful components such as plasma proteins to the filter element during blood treatment is suppressed, and the recovery rate of useful components tends to be improved. Further, when the specific surface area is 0.8 m ² /g or more, the adsorption amount of leukocytes and the like increases, so the ability to remove leukocytes and the like tends to improve.
The specific surface area of the first filter layer is more preferably 1.0 m ² /g or more and 3.2 m ^{2 /g or less, still more preferably 1.1 m 2 /} g or more and 2.9 m ² /g or less, and particularly preferably 1.0 m 2 /g or more and 3.2 m 2 /g or less. It is 2 m ² /g or more and 2.9 m ² /g or less, most preferably 1.2 m ² /g or more and 2.6 m ² /g or less.

The specific surface area is the surface area of the first filter layer per unit mass, and is a value measured by the BET adsorption method using krypton as the adsorbed gas. Is possible.
It indicates that the larger the specific surface area of the first filter layer, the larger the area capable of adsorbing cells, plasma proteins, etc. when treating blood using a filter layer of the same mass.

(ventilation resistance)
Airflow resistance of the first filter layer is preferably 25 Pa·s·m/g or more and 100 Pa·s·m/g or less, more preferably 30 Pa·s·m/g or more and 90 Pa·s·m/g or less, and still more preferably is 40 Pa·s·m/g or more and 80 Pa·s·m/g or less.
If the ventilation resistance is 25 Pa·s·m/g or more, the number of times of contact with leukocytes tends to increase, making capture of leukocytes easier. When the ventilation resistance is 100 Pa·s·m/g or less, clogging of blood cells tends to decrease and the processing speed tends to improve.

The ventilation resistance of the first filter layer is a value measured as a differential pressure generated when a constant flow rate of air is passed through the first filter layer, and is measured by an air permeability tester (for example, manufactured by Kato Tech KK, KES- The first filter layer was placed on the ventilation holes of F8-AP1), and the pressure loss (Pa·s/m) generated when air was passed through for about 10 seconds at a flow rate of 4 mL/cm ² /sec was measured. , is the value obtained by dividing the obtained pressure loss by the basis weight (g/m ² ) of the first filter layer. However, the cut-out part is changed and the measurement is performed 5 times, and the average value is taken as the ventilation resistance.
High ventilation resistance of the first filter layer means that air is difficult to pass through and the fibers constituting the first filter layer are densely or uniformly entangled. It shows that it has the property that it is difficult to flow. Conversely, the fact that the airflow resistance of the first filter layer is low means that the fibers constituting the first filter layer are coarse or unevenly entangled, and the first filter layer has the property that blood products easily flow. indicates that it has

(Average flow pore diameter)
The first filter layer preferably has an average flow pore size of less than 8.0 μm. If the average flow pore size is less than 8.0 μm, the number of times of contact with leukocytes tends to increase, facilitating capture of leukocytes. When the average flow pore size is 1.0 μm or more, blood cell clogging tends to decrease and the processing speed tends to increase. The average flow pore size is more preferably 1.5 μm or more and 7.5 μm or less, still more preferably 2.5 μm or more and 7.0 μm or less, particularly preferably 3.5 μm or more and 6.5 μm or less, and most preferably 4.5 μm or more6.5 μm. 5 μm or less.

The average flow pore size of the first filter layer can be measured using a perm porometer CFP-1200AEXS (automatic pore size distribution measurement system for porous materials) manufactured by PMI in accordance with ASTM F316-86.

(critical wetting surface tension)
The critical wetting surface tension (CWST) of the first filter layer is preferably 70 dyn/cm or higher, more preferably 75 dyn/cm or higher. The first filter layer having such a critical wetting surface tension ensures stable wettability with blood, thereby allowing efficient removal of leukocytes and the like while allowing platelets in the blood product to pass through. Although the upper limit of CWST is not particularly limited, it may be, for example, 200 dyn/cm, 150 dyn/cm, 100 dyn/cm, or the like.

CWST refers to a value obtained according to the following method. That is, aqueous solutions of sodium hydroxide, calcium chloride, sodium nitrate, acetic acid, or ethanol with different concentrations are prepared so that the surface tension changes by 2 to 4 dyn/cm. The surface tension (dyn/cm) of each aqueous solution is 94-115 for sodium hydroxide aqueous solution, 90-94 for calcium chloride aqueous solution, 75-87 for sodium nitrate aqueous solution, 72.4 for pure water, and 38- for acetic acid aqueous solution. 69 and 22 to 35 are obtained with an aqueous ethanol solution (“Kagaku Binran, Basic Edition II” Revised 2nd Edition, edited by The Chemical Society of Japan, Maruzen, 1975, p. 164). Ten drops of each aqueous solution having a different surface tension of 2 to 4 dyn/cm are placed on the non-woven fabric in descending order of surface tension and allowed to stand for 10 minutes. After standing for 10 minutes, the wet state is defined as 9 out of 10 drops or more absorbed by the nonwoven, and the non-wet state is defined as less than 9 out of 10 drops absorbed. In this way, when the non-woven fabric is sequentially measured from the liquid having the smallest surface tension, the wet state changes to the non-wet state along the way. At this time, the average value of the surface tension value of the liquid observed last in the wet state and the surface tension value of the liquid first observed in the non-wet state is defined as the CWST value of the nonwoven fabric. For example, when wetted with a liquid having a surface tension of 64 dyn/cm and not wetted with a liquid having a surface tension of 66 dyn/cm, the CWST value of the nonwoven fabric is 65 dyn/cm.

(average fiber diameter)
The nonwoven fabric contained in the first filter layer preferably has an average fiber diameter of 0.3 μm to 3.0 μm, more preferably 0.5 μm to 2.5 μm. By setting it in such a range, leukocyte removal performance can be improved while avoiding clogging.

Average fiber diameter refers to the value determined according to the following procedure.
That is, from the nonwoven fabric that actually constitutes the filter layer, or from one or more nonwoven fabrics that are substantially the same as this, a portion that is recognized to be substantially uniform is sampled at several locations, and the sampled nonwoven fabric A photograph of the fiber is taken using a scanning electron microscope to capture its diameter.
Continue taking pictures until a total of 100 diameters have been taken. For the photograph thus obtained, measure the diameter of all the fibers in the photograph. The diameter here means the width of the fiber in the direction perpendicular to the fiber axis. The average fiber diameter is obtained by dividing the sum of all measured fiber diameters by the number of fibers. However, if multiple fibers overlap and the diameter cannot be measured accurately due to the shadow of other fibers, or if multiple fibers melt and become thicker, the diameter will be significantly reduced. If different fibers are mixed, if the photo is out of focus and the fiber boundaries are not clear, etc., these data are not counted.
Also, if the filter layer contains a plurality of non-woven fabrics, if the fiber diameters measured in each non-woven fabric are clearly different, since they are different types of non-woven fabrics, find the interface between the two and Separately re-measure the average fiber diameter of Here, "clearly different average fiber diameters" means a case where a statistically significant difference is observed.

(The bulk density)
The bulk density of the first filter layer is preferably 0.05-0.50 g/cm ³ , more preferably 0.07-0.40 g/cm ³ , still more preferably 0.10-0.30 g / ^cm3 . When the bulk density of the first filter layer is 0.50 g/cm ³ or less, the flow resistance of the first filter layer is reduced, clogging with blood cells is reduced, and the treatment speed tends to be improved. In addition, when the bulk density is 0.05 g/cm ³ or more, the number of times of contact with leukocytes tends to increase, leukocytes and the like tend to be captured more easily, and the mechanical strength of the first filter layer increases. I have something to do.

The "bulk density of the first filter layer" is obtained by cutting out a nonwoven fabric with a size of 2.5 cm × 2.5 cm from a portion that is considered to be homogeneous, and measuring the basis weight (g/m ² ) and thickness (cm) by the method described later. Then divide the basis weight by the thickness. However, the area to be cut out is changed, and the basis weight and thickness are measured three times, and the average value is taken as the bulk density.

The basis weight of the first filter layer is 2.5 cm x 2.5 cm. Sample the non-woven fabric from a place that seems to be homogeneous, measure the weight of the non-woven fabric piece, and convert it to the mass per unit square meter. It is required by In addition, the thickness of the first filter layer is obtained by sampling the nonwoven fabric from a portion of a size of 2.5 cm × 2.5 cm that seems to be homogeneous, and measuring the thickness of the center (one point) with a constant pressure thickness meter. be done. The pressure applied by the constant-pressure thickness gauge is 0.4 N, and the area of the measurement part is 2 cm ² .

(Non-crystallization heat quantity and crystal melting heat quantity)
Blood processing filters are usually sterilized by steam heat treatment before use. At this time, it is considered that the physical structure of the nonwoven fabric contained in the filter layer is greatly changed by the steam heat treatment. Above all, if shrinkage occurs in the planar direction of the non-woven fabric, for example, in a blood processing filter having a structure such as that shown in FIGS. may decline.

From this point of view, the non-crystallized heat quantity of the nonwoven fabric contained in the filter layer before the steam heat treatment is preferably 5 J/g or less, more preferably 3 J/g or less, still more preferably 2 J/g or less, and particularly preferably It is 1 J/g or less. "Amount of heat for uncrystallization" is an index showing the degree of crystallinity of a resin, and the smaller the value, the higher the degree of crystallinity of the resin.

By using a filter layer using a nonwoven fabric that satisfies the amount of heat for non-crystallization, filtration performance and handleability as a blood treatment filter are improved.
For example, in a blood treatment filter in which a filter medium including a filter layer is sandwiched between rigid containers as shown in FIGS. As a result, a firm clamping state between the container gripping portion and the filter medium is maintained, so that the side leak phenomenon can be suppressed and the ability to remove leukocytes and the like can be improved. Note that the side leak phenomenon is a phenomenon in which blood slips through between the holding portion and the filter medium without penetrating the filter medium, and flows from the inlet space to the outlet space.

In the case of a blood treatment filter in which the filter material is sandwiched between flexible containers and the container and the filter material are joined by high-frequency welding, by controlling the amount of uncrystallized heat of the non-woven fabric to a certain level or less, the container and the filter material are joined together. The strength of the part is improved, and the centrifugal resistance of the blood processing filter (when the blood processing filter is subjected to centrifugal processing (when centrifugal force is applied), the joint between the container and the filter medium is less likely to break). do. It is not clear why the strength of the high-frequency welded joint between the container and the filter material is improved by controlling the uncrystallized heat amount of the nonwoven fabric contained in the filter layer to a certain level or less. By increasing the repulsive force of the non-woven fabric, it is possible to suppress excessive melting due to pressure bonding of the non-woven fabric and form a homogeneous joint (without depression holes caused by excessive melting). .

Furthermore, the non-woven fabric contained in the filter layer has a value obtained by subtracting the non-crystallization heat quantity from the crystal melting heat quantity before the steam heat treatment is preferably 50 J/g or more, more preferably 55 J/g or more, and still more preferably. is at least 60 J/g, particularly preferably at least 65 J/g. This "value obtained by subtracting the heat of uncrystallization from the heat of fusion of crystals" is also an index showing the degree of crystallinity of the resin, and the larger this value is, the higher the degree of crystallinity of the resin is. By further increasing the crystallinity, changes in the physical properties (shrinkage, etc.) of the filter layer before and after the steam heat treatment are further suppressed, and the ability to remove leukocytes and the like increases as described above.

The amount of heat for non-crystallization and the amount of heat for crystal melting are values measured by a differential scanning calorimeter method (DSC method) for a nonwoven fabric (fiber base material). The measuring method is explained below.
3 to 4 mg of nonwoven fabric (fiber base material) is separated and set in an aluminum standard container, and the initial temperature rise curve (DSC curve). From this initial temperature rise curve (DSC curve), an exothermic peak and a melting peak (endothermic peak) are detected, and the heat value (J) obtained from each peak area is divided by the mass of the non-woven fabric. /g) and the heat of crystal fusion (J/g) are calculated.
As a measuring device, for example, a TA-60WS system manufactured by Shimadzu Corporation can be used.

(X-ray crystallinity)
In this embodiment, the nonwoven fabric contained in the filter layer preferably has an X-ray crystallinity of 60 or higher, more preferably 63 or higher, and even more preferably 66 or higher before the steam heat treatment. The crystallinity of the nonwoven fabric is further increased, and changes in physical properties (shrinkage, etc.) of the filter layer before and after the steam heat treatment are suppressed, thereby increasing the ability to remove leukocytes and the like as described above.

X-ray crystallinity is measured by an X-ray diffraction method.
The measurement can be performed using an X-ray diffractometer (for example, MiniFlex II (Rigaku, model number 2005H301)) according to the following measurement procedures 1) to 5).
1) A piece of nonwoven fabric (fiber base material) having a size of 3 cm x 3 cm is set on a sample table.
2) Perform measurement under the following conditions.
・Scanning range: 5° to 50°
・Sampling width (width to capture data): 0.02°
・Scan speed: 2.0°/min ・Voltage: 30 kV
・Current: 15mA
3) After the measurement, obtain data in which the peaks of the amorphous part and the crystal part are separated.
4) Obtain the amorphous peak area (Aa) and the total peak area (At) from the data in 3). For example, the data measured in 3) is opened with analysis software (MDI JADE 7), and the "automatic peak separation" function is performed. As a result, the amorphous peak area (Aa) and total peak area (At) are automatically calculated.
5) From the amorphous peak area (Aa) and the total peak area (At), the degree of crystallinity is calculated by the following formula.
Crystallinity (%) = (At-Aa) / At x 100

A nonwoven fabric with a non-crystallization heat quantity of 5 J/g or less, a non-woven fabric with a value obtained by subtracting the non-crystallization heat quantity from the crystal melting heat quantity of 50 J/g or more, and an X-ray crystallinity of 60 or more before the steam heat treatment. The nonwoven fabric can be easily produced by selecting the material and production conditions as described below.

(Area shrinkage rate)
In the present embodiment, the area shrinkage of the nonwoven fabric is preferably 10% or less, more preferably 3% or less, particularly preferably 2% or less, and most preferably 1% or less. When the area shrinkage ratio is 10% or less, the uniformity of the pore size is maintained even after the sterilization treatment, fluctuations in the treatment speed can be prevented, and a stable performance balance tends to be exhibited, which is preferable.
In this respect, polybutylene terephthalate has a faster crystallization rate than other polyester fibers, such as polyethylene terephthalate fiber, so it is easy to increase the crystallinity, so severe steam heat treatment such as high temperature and high pressure sterilization is performed. However, shrinkage in the plane direction is difficult to occur (easily to reduce the area shrinkage ratio), and therefore stable leukocyte removal ability and processing speed can be exhibited regardless of the sterilization conditions.

The area shrinkage rate of a nonwoven fabric is obtained by measuring the vertical and horizontal dimensions of a nonwoven fabric (fiber base material) cut into a square of about 20 cm x 20 cm, and then holding the nonwoven fabric at 115 ° C for 240 minutes without fixing it with a pin or the like. It is calculated by the following formula after performing heat treatment and then measuring the vertical and horizontal dimensions again.
Area shrinkage rate (%)
= (Vertical length of nonwoven fabric before heat treatment (cm) x Horizontal length of nonwoven fabric before heat treatment (cm)
- Vertical length of non-woven fabric after heat treatment (cm) × Width length of non-woven fabric after heat treatment (cm))
÷ (Vertical length of nonwoven fabric before heat treatment (cm) x Width length of nonwoven fabric before heat treatment (cm)) x 100

When a blood processing filter is produced by sandwiching and gripping a filter medium between two parts of a container material on the outlet side and the inlet side that constitute a hard container (for example, the cases shown in FIGS. 1 and 2 ), when the filter material contains a plurality of nonwoven fabrics, a nonwoven fabric having a high degree of crystallinity is used as the nonwoven fabric in contact with the outlet side container material (the nonwoven fabric located closest to the outlet side container material). In this way, the grasping portion of the container material on the outlet side after the steam heat treatment clamps the filter material more strongly, and as a result, the blood does not penetrate the filter medium, but passes between the grasp portion and the filter medium, and enters the inlet. It is possible to suppress the phenomenon of direct flow from the inner space to the outlet space (side leak phenomenon), improve the ability to remove leukocytes, etc., and further improve the performance as a blood processing filter.

That is, when a blood processing filter is produced by sandwiching and gripping a filter medium between two parts, ie, an outlet side and an inlet side container material that constitute a hard container, the nonwoven fabric contained in the filter medium includes: The nonwoven fabric that contacts the outlet side container material preferably has the following (1), and more preferably has (2) and/or (3) in addition to (1).
(1) Heat quantity for uncrystallization before steam heat treatment is 5 J/g or less (2) Heat quantity for crystal melting minus heat quantity for uncrystallization before steam heat treatment is 50 J/g or more (3) Steam X-ray crystallinity of 60 or more before heat treatment

In addition, when a blood processing filter is produced by sandwiching and gripping a filter medium between two parts of container materials on the outlet side and the inlet side that constitute a hard container, the crystallinity of all nonwoven fabrics contained in the filter medium If the is high, it is excellent from the viewpoint of the ability to remove leukocytes and the like after steam heat treatment, but the repulsive strength of the filter medium increases, making it difficult to grip or join the filter medium between container materials. From the viewpoint of productivity during production, among the nonwoven fabrics contained in the filter medium, nonwoven fabrics in contact with the inlet side container material and the outlet side container material (or the inlet side container material and the outlet side container material The crystallinity of the nonwoven fabric other than the nonwoven fabric in contact with the nonwoven fabric and a predetermined number of nonwoven fabrics (usually one to several) placed adjacent thereto is rather preferably not too high.
For example, when the filter material held in the hard container includes a second filter layer (described later) and a first filter layer in order from the inlet side, the outlet of the plurality of nonwoven fabrics contained in the first filter layer The nonwoven fabric in contact with the part-side container material (and a predetermined number of nonwoven fabrics arranged adjacent thereto) satisfies at least the above (1), and part or all of the other nonwoven fabrics meet the above (1). From the viewpoint of productivity when manufacturing a blood treatment filter, the pre-steam heat treatment non-woven fabric in contact with the outlet side container material does not satisfy preferred from

[Second filter layer]
The blood processing filter may include additional filter layers in addition to the first filter layer as long as the effects of the present invention are not impaired. For example, the blood processing filter may further include one or more second filter layers between the inlet portion of the container and the first filter layer.

The second filter layer preferably has a structure suitable for removing microaggregates contained in blood. Preferably, the second filter layer comprises a nonwoven fabric. As the material of the nonwoven fabric, for example, the same material as that of the nonwoven fabric contained in the first filter layer can be used.

The average fiber diameter of the nonwoven fabric contained in the second filter layer is preferably 3 μm to 60 μm, more preferably 4 μm to 40 μm, still more preferably 30 μm to 40 μm, from the viewpoint of removing microaggregates in blood. / or between 10 μm and 20 μm.

In the embodiment in which the second filter layer is arranged upstream of the first filter layer, even when aggregates are generated in the blood, the non-woven fabric of the second filter layer on the upstream side (inlet side) with coarser mesh Agglomerates are captured, and aggregates reaching the nonwoven fabric of the first filter layer on the finer-mesh downstream side (outlet part side) are reduced. Therefore, clogging of the first filter layer by aggregates is suppressed.

The bulk density of the second filter layer is preferably 0.05-0.50 g/cm ³ , more preferably 0.10-0.40 g/cm ³ . When the bulk density of the second filter layer is 0.50 g/cm ³ or less, clogging of the nonwoven fabric due to capture of aggregates, leukocytes, etc. is suppressed, and the filtration rate tends to improve. In addition, when the bulk density of the nonwoven fabric is 0.05 g/cm ³ or more, the ability to capture aggregates increases, clogging of the nonwoven fabric in the first filter layer is suppressed, and the filtration rate tends to improve. , the mechanical strength of the nonwoven fabric tends to improve.

[Third filter layer]
The filter material of the blood processing filter may further include one or more third filter layers between the first filter layer and the outlet of the container as long as the effects of the present invention are not impaired.
Also, the filter medium of the blood processing filter further comprises one or more second filter layers between the inlet portion of the container and the first filter layer, and one or more second filter layers between the first filter layer and the outlet portion of the container. may further include a third filter layer of

The configuration of the third filter layer may be appropriately adjusted according to the required performance.

The third filter layer preferably contains known filtration media such as fibrous porous media such as non-woven fabrics, woven fabrics and meshes, or porous bodies having three-dimensional network continuous pores. Examples of these materials include polypropylene, polyethylene, styrene-isobutylene-styrene copolymer, polyurethane, polyester, and the like. It is preferable that the third filter layer contains a nonwoven fabric from the viewpoint of productivity and welding strength of the blood treatment filter. It is particularly preferable that the third filter layer has a plurality of protrusions formed by embossing or the like, because the blood flow becomes more uniform.

The nonwoven fabric contained in the third filter layer preferably has an average fiber diameter of 3 μm to 60 μm, more preferably 4 μm to 40 μm, even more preferably 30 μm to 40 μm and/or 10 μm to 20 μm.

In the case of a blood processing filter having a flat and flexible container, when the third filter layer is arranged, the filter layer is pressed against the outlet side container by the positive pressure on the inlet side generated during filtration. It is also preferable because it prevents the outlet-side container from being in close contact with the filter layer due to the negative pressure on the outlet-side, which prevents blood flow from being obstructed, and also enhances the weldability between the flexible container and the filter layer.

Each nonwoven fabric constituting the filter layer may have its surface modified by known techniques such as coating, chemical treatment, radiation treatment, etc. for the purpose of controlling selective separation of blood cells and hydrophilicity of the surface.

<Method for producing the first blood treatment filter>
The method for producing the nonwoven fabric (fiber base material) is not limited, and it can be produced by either a wet method or a dry method. From the viewpoint of stably obtaining a nonwoven fabric having a suitable maximum orientation ratio, it is particularly preferable to adopt the melt blowing method.

An example of a melt blowing method will be described as a method for producing a nonwoven fabric (fiber base material). In the melt-blowing method, a molten polymer flow melted in an extruder is filtered through a suitable filter, introduced into a molten polymer inlet of a melt-blowing die, and then discharged from an orifice-shaped nozzle. At the same time, the heated gas introduced into the heated air introduction part is led to the heated air ejection slit formed by the melt blow die and the lip, and is ejected from here to thin the ejected molten polymer to form ultrafine fibers. Then, a nonwoven fabric is obtained by laminating the formed ultrafine fibers. Furthermore, if the nonwoven fabric is heat-treated using a heat suction drum, a hot plate, hot water, a hot air heater, or the like, a nonwoven fabric having a desired degree of crystallinity can be obtained.

The method for producing a nonwoven fabric having a maximum orientation ratio of 1.2 or more is not particularly limited. There are ways to speed it up. When the winding speed is increased, the fibers are strongly oriented in the winding direction of the conveyer (longitudinal direction), and the difference in the degree of orientation in the direction perpendicular thereto (width direction) becomes relatively large.

When the above method is used, a nonwoven fabric having a small weight per unit area (basis weight) and a small thickness can be obtained. . Alternatively, if the conveyor is designed to collect the nonwoven fabric in a circulating manner, it is possible to collect a nonwoven fabric with a predetermined basis weight by repeatedly blowing the nonwoven fabric on the conveyor. In this method, when assembling the filter medium, the nonwoven fabric is easy to handle due to its high basis weight, and the number of laminated layers does not need to be excessively increased, thereby improving the production efficiency of the filter medium.

Another possible method is to reduce the amount of polymer ejected from one spinneret per unit time (the amount of polymer ejected from a single hole). When the discharge amount is reduced, the fibers constituting the nonwoven fabric become thin, so the fibers are strongly oriented in the winding direction of the conveyor. However, if the average fiber diameter of the fibers changes, the leukocyte removal rate and the filtration time will be affected by the change, so it is preferable not to change the ejection amount significantly.

It is also effective to use a polymer with a low intrinsic viscosity so that the resin can be stretched thinner. For example, among polyesters, polybutylene terephthalate resin generally has a lower melting point and melt viscosity than polyethylene terephthalate. Cheap. Regarding the selection of resin, the melting point of copolymers and polymers containing impurities such as additives tends to be lower than that of so-called homopolymers, so these resins should be selected appropriately. It is also possible to optimally adjust the melt viscosity.

More specifically, a nonwoven fabric having a maximum orientation ratio of 1.2 or more can be produced by using a PBT resin under the following conditions.
・Collection conveyor speed: 4.0 to 6.0 (m/sec)
・Single hole discharge amount: 0.10 to 0.21 (g/(min・hole))
・Intrinsic viscosity (IV): 0.63 to 0.82 (dL/g)
・Die temperature: 270 to 290 (°C)
・Air pressure: 0.25 to 0.40 (MPa)
In the above case, it is known that the melt viscosity (shear rate 100 (1/sec), 280° C.) is 100 to 500 (Pa·s).
Among these, practically, it is effective to first set the intrinsic viscosity, the single-hole discharge rate, and the die temperature, and then adjust the conveyor speed while confirming the degree of orientation. The reason is that depending on the melt viscosity of the resin, which depends on the intrinsic viscosity and the die temperature, a strong pressure is applied to the die when it is discharged, and the die may break, so the single hole discharge rate must be set low. because it may not be possible. In addition, setting the die temperature to 290° C. or less is preferable in the case of PBT because discoloration of the fiber due to resin decomposition can be suppressed.
However, since the single hole discharge rate is a parameter that is directly linked to the average fiber diameter of the nonwoven fabric, it is necessary to adjust the pressure of the heated air as well in order to obtain a predetermined average fiber diameter when the discharge rate is changed. . For example, when the discharge rate is lowered, the average fiber diameter can be maintained by lowering the pressure of the heating air. In addition, after setting the single hole discharge rate, it is necessary to calculate and set the collection time on the conveyor in order to obtain a predetermined nonwoven fabric weight. That is, since the single-hole discharge amount also affects the production amount of the nonwoven fabric, it is necessary to return to the selection of the resin and the discharge amount again when considering the productivity and quality of the nonwoven fabric.
Finally, although the nozzle-to-conveyor distance does not significantly affect the orientation ratio of the nonwoven, it is important as a means of controlling the thickness of the nonwoven. The thickness can be reduced by adjusting the distance between the nozzle and the conveyor, generally within the range of 3 to 60 cm. In particular, when the average fiber diameter is 1 to 3 μm, the bulk density can be easily adjusted to 0.10 to 0.30 g/cm ³ by adjusting the distance between the nozzle and the conveyor to 3 to 10 cm. be.

<Second blood processing filter>
One embodiment of the present invention comprises a container having a blood inlet and an outlet;
a filter medium disposed within the container between the inlet and the outlet;
A blood processing filter comprising:
The filter medium includes one or more filter layers (hereinafter also referred to as "first filter layer"),
The filter layer has a space with a maximum length of 50 μm or more in the plane direction and a maximum length of 15 μm or more in the thickness direction in a cross section in the thickness direction.
It relates to the blood processing filter.
By having a predetermined space inside the first filter layer, an excellent leukocyte removal rate and an excellent filtration time (filtration rate) can be exhibited.

[container]
The container is as described in <First blood processing filter>.

[Filter medium]
(First filter layer)
The filter medium includes one or more first filter layers. When the filter medium includes multiple first filter layers, each of the multiple first filter layers may be the same or different. Examples of the thickness of the first filter layer include 0.1 mm to 0.8 mm, 0.3 mm to 0.6 mm, and 0.4 to 0.5 mm. Considering the variation in physical properties during spinning, sampling is performed at at least three points in the spinning width direction (for example, one point between the left end and the center, one point near the center, and one point between the center and the right end). By doing so, the average thickness of the first filter layer can be measured. The size of the sample is 2.5 cm×2.5 cm, and the thickness is obtained by measuring the center (one point) with a constant pressure thickness gauge. The pressure applied by the constant-pressure thickness gauge is 0.4 N, and the area of the measurement part is 2 cm ² . If the spinning width direction cannot be specified, the part used as the filter filtration part is sampled and measured.

Preferably, the first filter layer comprises a nonwoven fabric. The nonwoven fabric is as described in <First blood treatment filter>.

The nonwoven fabric contained in the first filter layer may have a coat layer on its surface. The coat layer is as described in <First blood processing filter>.

The nonwoven fabric contained in the first filter layer preferably has basic nitrogen-containing functional groups on its peripheral surface portion. The peripheral surface portion of the nonwoven may further have nonionic hydrophilic groups. The basic nitrogen-containing functional group and the nonionic hydrophilic group are as described in <First blood treatment filter>.

(internal space)
The first filter layer has a space with a maximum length of 50 μm or more in the plane direction and a maximum length of 15 μm or more in the thickness direction in a cross section in the thickness direction (a cut surface cut in the thickness direction) (for example, 8A and 8B). By having a space of such a size, clogging due to blood cells, microaggregates, etc. contained in blood can be avoided, and by increasing the effective filtration area, leukocyte removal performance and filtration time can be improved. can. When the filter medium includes a plurality of first filter layers, at least one first filter layer should have the internal space, but it is preferable that all the first filter layers have the internal space. .

The maximum length of the space in the plane direction is preferably 50 μm to 2000 μm, more preferably 100 μm to 1500 μm, still more preferably 200 μm to 1000 μm.
The maximum length of the space in the thickness direction is preferably 15 μm to 200 μm, more preferably 15 μm to 150 μm, still more preferably 20 μm to 100 μm.
By setting the upper limits of the maximum lengths in the planar direction and the thickness direction as described above, it is possible to suppress uneven blood flow and further increase the effective filtration area. In addition, it is possible to prevent blood from remaining inside the first filter layer, thereby avoiding a decrease in the amount of collected blood.

The internal space of the first filter layer can be measured by the following method. The size of the internal space of the first filter layer does not substantially change between the state in which the first filter layer is stored in the blood processing filter and the state in which the first filter layer is removed from the blood processing filter.
From one first filter layer, a portion having average physical properties (breathing resistance, density, etc.) of the filter layer is sampled. Specifically, considering the variation in physical properties during spinning, at least three locations in the spinning width direction (for example, one location from the left end to the center, one location near the center, and one location from the center to the right end) point), and measure the internal space of the cross section in the thickness direction of the sample. If the spinning width direction cannot be specified, a sample is taken from the part used as the filter filtration part.
The length of the internal space is determined using SEM (ProX) pore size analysis software (PHENOM POROMETRIC) manufactured by Phenom World. The vacancy detection conditions are initial setting conditions of the software described below. However, if detection is insufficient, such as when holes overlap, the hole detection conditions (Min Contrast, Merge Shared borders, Conductance, Min Detection, etc.) may be appropriately adjusted.

The specific measurement method for the internal space is as follows.
(1) A sample of the first filter layer to be photographed has a size of about 10 mm×about 3 mm, and a 10 mm side is used for cross-sectional observation. Three samples with a size of about 10 mm×about 3 mm are used for measurement.
At this time, the first filter layer is cut so as not to crush the cross section of the sample. Since it is necessary to observe while maintaining the three-dimensional structure of the first filter layer, a solution that wets the first filter layer (e.g., water or 20% ethanol water. If the hydrophilicity is low, it is preferable to use ethanol water.) ), then immersed in liquid nitrogen, and the fully frozen first filter layer is broken.
If the fibers do not break when folded (for example, when the fibers are bent without being cut or when the first filter layer is too small to fold or split), a fixing resin (epoxy resin etc.) is poured between the fibers and solidified, then the cross section is polished and observed.
(2) The photographing magnification is such that the entire thickness of the first filter layer can be observed (preferably 100 times). The magnification can be optimized according to the thickness of the first filter layer and the size of the internal space.
(3) Three cross-sectional images are taken for each sample. Using the pore size analysis software (PHENOM POROMETRIC), the pore size in the plane direction and the pore size in the thickness direction are determined for the cross-sectional image. Let the average value of the maximum spatial length of 9 points of each cross-sectional photographed image be the maximum spatial length.

The initial setting values of the pore size analysis software (PHENOM POROMETRIC) are as follows.
Min shared borders: 0.3
Exclude edge particles: not selected Conductance: 0.3
Min detection size: 2.5
Foreground kernel size: 15
Segment anisotropic diffuse conductance: 10
Segment anisotropic diffuse iterations: 5
Segment gradient function type: normal
Segmenter WS lower threshold: 0.001
Merging min size ratio: 2
Merging kernel size: 3

(Porosity)
The in-plane porosity of the first filter layer preferably varies in the thickness direction. The in-plane porosity means the ratio of voids existing in a plane corresponding to a predetermined position in the thickness direction. A high in-plane porosity means a low in-plane fiber density. Specifically, when the in-plane porosity is 1, it means that there are no fibers in the plane. The fluctuation of the in-plane porosity is, for example, the ratio of the voids existing in the plane corresponding to the first position in the thickness direction and the ratio of the voids existing in the plane corresponding to the second position in the thickness direction. is different.

For example, FIG. 9 shows the in-plane porosity in the thickness direction of the nonwoven fabric of Example A1. "Position" in FIG. 9 represents a predetermined position in the thickness direction (distance from the surface of the first filter layer), and "porosity" is the porosity present in the plane corresponding to the predetermined position in the thickness direction. represents FIG. 9 shows that the in-plane porosity varies in the thickness direction. On the other hand, FIG. 11 shows the in-plane porosity in the thickness direction of the nonwoven fabric of Comparative Example A1, and the variation in the in-plane porosity is small. By varying the in-plane porosity in the thickness direction, clogging can be avoided not only in the internal space contained in the first filter layer but also in the first filter layer as a whole.

The smallest in-plane porosity in the thickness direction excluding the portions up to 80 μm from both ends is referred to as the “minimum in-plane porosity”, and the largest in-plane porosity is referred to as the “maximum in-plane porosity”. The difference between the minimum in-plane porosity and the maximum in-plane porosity is preferably 0.08 to 0.28, more preferably 0.10 to 0.20. By setting it to such a range, it is possible to exhibit excellent leukocyte removal performance while avoiding clogging. In addition, the reason why the portion up to 80 μm from both ends in the thickness direction is excluded is that the porosity of the portion cannot be stably measured due to the influence of fluffing of fibers in the vicinity of the surface of the first filter layer.

The in-plane minimum porosity and the in-plane maximum porosity may be appropriately changed according to the blood to be treated. For example, when processing highly viscous blood, a higher porosity may be used to avoid clogging. On the other hand, when treating blood with low viscosity and a large number of white blood cells, the porosity should be lowered in order to improve the white blood cell removal performance. Although not particularly limited, the in-plane minimum porosity is preferably 0.72 to 0.85, more preferably 0.75 to 0.83. The in-plane maximum porosity is preferably 0.85 to 1.00, more preferably 0.87 to 0.95.

The in-plane porosity in the thickness direction of the first filter layer can be measured by the following method.
From one first filter layer, at least three locations in the spinning width direction (for example, one location from the left end to the center, one location from the center, and the center to the right end) ) and the porosity of the sample is calculated by X-ray CT measurement. When the spinning width direction cannot be specified, sampling is performed at three points from the portion used as the filtering portion. The X-ray CT apparatus and image analysis software used are as follows.
X-ray CT device Rigaku Co., Ltd. High-resolution 3D X-ray microscope nano3DX
Image analysis software ImageJ
A sample for X-ray CT measurement is cut into 2.5 mm×2.5 mm in-plane, and the X-ray CT measurement is performed while keeping the entire thickness. However, the measured thickness shall be 0.1 mm or more.
The measurement conditions are as follows.
Pixel resolution 0.54 μm/pix
Exposure time 18 seconds/sheet Number of projections 1500 sheets/180 degrees X-ray tube voltage 40 kV
X-ray tube current 30mA
X-ray target Cu
The thickness direction of the nonwoven fabric is defined as the Z axis, an arbitrary direction perpendicular to the Z axis as the X axis, and a direction perpendicular to the X and Z axes as the Y axis. The XY plane corresponds to the in-plane of the nonwoven fabric. For the X-ray measurement point in the sample, select the central portion in the plane where the cut surface at the edge of the sample does not affect the measurement.
From the tomogram image obtained from the X-ray CT measurement, the image is trimmed with a rectangular parallelepiped of X axis×Y axis×Z axis=500 μm×500 μm×thickness. Let this be a three-dimensional image 1 .
The median filter of the image processing method is applied to the three-dimensional image 1 under the condition of a radius of 2 pix, and then the Otsu method of the image processing method is applied to perform area division. The luminance value of the pixel is set to 0 for air and 255 for non-woven fiber. An image obtained in this manner is referred to as a three-dimensional image 2 .
Pixels with a luminance value of 255 in the three-dimensional image 2 were subjected to segmentation using an image processing method, and fibers with a pixel number of 10000 pixels or less among continuous fibers with a luminance value of 255 were removed as noise. The image obtained in this way is defined as a three-dimensional image 3 by setting the pixel luminance value to 0 for the air and 255 for the fiber of the non-woven fabric.
In this three-dimensional image 3, the two-dimensional porosity at each location of 1 pix along the Z-axis, which is the thickness direction, is obtained by the following equation.
Porosity=number of air (brightness value 0) pixels on the XY plane with a thickness of 1 pix/total number of pixels on the XY plane with a thickness of 1 pix This porosity is obtained for all pixels in the Z-axis direction (all in the thickness direction).
For at least one of the three samples, the minimum in-plane porosity, the maximum in-plane porosity, and the difference between them are preferably within the above numerical ranges.

(Filling rate)
The first filter layer preferably has a fill factor of 0.09 to 0.26, more preferably 0.12 to 0.19. When the filling rate of the first filter layer is 0.26 or less, clogging with blood cells and microaggregates is reduced, and the processing speed tends to be improved. In addition, since the filling rate of the first filter layer is 0.09 or more, the number of times of contact with leukocytes tends to increase and the capture rate of leukocytes tends to improve, and the mechanical strength of the filter medium is improved. tend to

The packing rate of the first filter layer is measured by the following method. The area, thickness, and mass of the cut first filter layer in the plane direction, and the specific gravity of the fibrous material constituting the nonwoven fabric of the first filter layer are measured and calculated by the following formula (10). The basis weight is determined by sampling a piece of nonwoven fabric of 2.5 cm x 2.5 cm from a portion that seems to be homogeneous, measuring the weight of the piece of nonwoven fabric, and converting it into mass per square meter. In addition, the thickness of the first filter layer is obtained by sampling the nonwoven fabric from a portion of a size of 2.5 cm × 2.5 cm that seems to be homogeneous, and measuring the thickness of the center (one point) with a constant pressure thickness meter. be done. The pressure applied by the constant-pressure thickness gauge is 0.4 N, and the area of the measurement part is 2 cm ² .
Filling rate = [mass (g) of the first filter layer ÷ {area in the plane direction of the first filter layer (cm ² ) × thickness of the first filter layer (cm)}] ÷ constituting the nonwoven fabric of the first filter layer Specific gravity of fiber material (g/cm ³ ) (10)

(formation index)
The formation index of the first filter layer is as described in <First blood processing filter>.

(Specific surface area)
The specific surface area of the first filter layer is preferably 0.50 m ² /g or more and 1.50 m ² /g or less. When the specific surface area is 1.50 m ² /g or less, adsorption of useful components such as plasma proteins to the filter layer during blood treatment is suppressed, and the recovery rate of useful components tends to be improved. Further, when the specific surface area is 0.50 m ² /g or more, the adsorption amount of leukocytes and the like increases, so the ability to remove leukocytes and the like tends to improve. The specific surface area of the first filter layer is more preferably 0.70 m ² /g or more and 1.45 m ² /g or less, still more preferably 1.10 m ² /g or more and 1.40 m ² /g or less.

The measurement of the specific surface area is as described in <First blood processing filter>.

(ventilation resistance)
The ventilation resistance of the first filter layer is as described in <First blood processing filter>.

(Average flow pore diameter)
The first filter layer preferably has an average flow pore size of less than 8.0 μm. If the average flow pore size is less than 8.0 μm, the number of times of contact with leukocytes tends to increase, facilitating capture of leukocytes. When the average flow pore size is 1.0 μm or more, blood cell clogging tends to decrease and the processing speed tends to increase. The average flow pore size is more preferably 1.5 μm or more and 7.5 μm or less, still more preferably 2.5 μm or more and 7.0 μm or less, and most preferably 3.5 μm or more and 6.0 μm or less.

The measurement of the average flow pore size is as described in <First blood processing filter>.

(critical wetting surface tension)
The critical wetting surface tension (CWST) of the first filter layer is preferably 70 dyn/cm or higher, more preferably 85 dyn/cm or higher, and even more preferably 95 dyn/cm or higher. The first filter layer having such a critical wetting surface tension ensures stable wettability with blood, thereby allowing efficient removal of leukocytes and the like while allowing platelets in the blood product to pass through. Although the upper limit of CWST is not particularly limited, it may be, for example, 200 dyn/cm, 150 dyn/cm, 100 dyn/cm, or the like.

The measurement of CWST is as described in <First blood processing filter>.

(average fiber diameter)
The average fiber diameter of the nonwoven fabric contained in the first filter layer is as described in <First blood treatment filter>.

[Second filter layer]
In addition to the first filter layer, the filter material of the blood processing filter may include additional filter layers as long as the effects of the present invention are not impaired. For example, the filter medium may further include one or more second filter layers between the inlet portion of the container and the first filter layer.

The second filter layer is as described in <First blood processing filter>. The filling rate of the second filter layer is preferably 0.04 to 0.36, more preferably 0.07 to 0.29. When the filling rate of the second filter layer is 0.36 or less, the clogging of the nonwoven fabric due to the capture of aggregates is suppressed, and the filtration rate tends to improve. On the contrary, when it is 0.04 or more, the ability to capture aggregates increases, clogging of the first filter layer is suppressed, the filtration rate tends to improve, and the mechanical strength of the nonwoven fabric improves. There is a tendency.

[Third filter layer]
The filter material of the blood processing filter may further include one or more third filter layers between the first filter layer and the outlet of the container as long as the effects of the present invention are not impaired. Also, the filter media of the blood processing filter further comprises one or more second filter layers between the inlet portion of the container and the first filter layer, and one or more second filter layers between the first filter layer and the outlet portion of the container. may further include a third filter layer of

The third filter layer is as described in <First blood processing filter>.

<Method for Manufacturing Second Blood Processing Filter>
The method for producing the nonwoven fabric (fiber base material) is not limited, and it can be produced by either a wet method or a dry method. When forming a desired space inside the first filter layer, it is preferable to employ a melt blowing method.

An example of a melt blowing method will be described as a method for producing a nonwoven fabric (fiber base material). In the melt-blowing method, a molten polymer flow melted in an extruder is filtered through a suitable filter, introduced into a molten polymer inlet of a melt-blowing die, and then discharged from an orifice-shaped nozzle. At the same time, the heated air introduced into the heated air introduction part is led to the heated gas ejection slit formed by the melt blow die and the lip, and is ejected from here to thin the ejected molten polymer to form ultrafine fibers. Then, the formed ultrafine fibers are laminated on a collecting conveyor or a collecting drum to obtain a nonwoven fabric. Further, if the nonwoven fabric is heat-treated using a heat suction drum, a hot plate, hot water, a hot air heater, high-pressure steam sterilization, or the like, a nonwoven fabric having a small shrinkage rate and a stable shape can be obtained.

When collection is performed using a rotating conveyor, it is possible to spin the laminated nonwoven fabric by spraying and stacking the fibers on the rotating conveyor. When collection is performed using a take-up belt conveyor, it is possible to spin a laminated nonwoven fabric by arranging multiple rows of spinnerets in the longitudinal direction without using a rotary system. Here, a predetermined space can be formed inside the filter layer by performing appropriate cooling until the fibers discharged from the spinneret and the newly discharged fibers overlapping the fibers are laminated. . As a cooling method, for example, there is a method of extending the time until the fiber layer is laminated on the fiber layer to naturally cool the fiber layer. On the other hand, if the conveyor has a suction function, the fibers can be stably collected and a cooling effect can be obtained by ventilating the fibers. If the cooling is excessive, the fibers are not fused at all and the fiber layer is peeled off, making it impossible to form a single nonwoven fabric. will come to

The internal space of the filter layer can be adjusted by appropriately adjusting the number of rotations of the collection conveyor, the length of the melt blow die, the spinning width, the distance (DCD) between the melt blow die and the collection drum, and the like.

Desirable spinning conditions for the nonwoven fabrics described herein include the following conditions.
・Melt blow die spinneret number: 5 to 30 (hole/cm)
・Collection conveyor rotation speed: 100 to 400 (m/min)
・Discharge movement speed: 0.06 to 0.10m/s
・Single hole discharge rate: 0.12 to 0.20 (g/(min・hole))
・Amount of heating air: 100 to 400 (Nm ³ /hr)
・DCD: 50 to 1000 (mm)
Among these, the most important conditions are the conveyor rotation speed and the discharge movement speed.

The means for laminating the nonwoven fabric while rotating the collection conveyor in the longitudinal direction of the nonwoven fabric can reduce the amount of nonwoven fabric applied per unit time and unit area, and relatively increase the internal space of the filter layer. Therefore, it is valid. In particular, increasing the rotation speed has the effect of improving the homogeneity of the nonwoven fabric and increasing the internal space of the filter layer.

Moreover, the means for discharging fibers from the spinneret in the width direction at different times instead of simultaneously discharging the fibers from the spinnerets in the width direction is effective because the internal space in the plane direction can be increased. The principle is that when the ejection area reciprocates, by providing a time interval between the previous ejection and the subsequent ejection, the cooling of the previous fiber layer progresses during that time, making it difficult to fuse with the subsequent fiber layer. As a result, the internal space in the planar direction can be increased. The effect is even greater if the time interval is large.

In addition, by reducing the discharge movement speed, the previous fiber layer is cooled, so that the internal space in the planar direction can be increased. Here, the discharge moving speed means the moving speed of the discharged spinneret region in the width direction per unit time, which is calculated by the following formula.
<Formula>
Discharge movement speed = Width length of collection conveyor (m) / (switching time (s) x number of spinnerets in width direction)
For example, in FIG. 13, it is assumed that the collection conveyor has a width of 1.6 m and eight spinnerets with a width of 20 cm are installed. In this case, when spinning is continuously performed while switching every 2.5 seconds from the right end spinneret 1 to the left end spinneret 8 in FIG. ×8)=0.08 m/s. This ejection movement speed indicates the net speed at which the ejection area spreads in the width direction.
If you want to obtain the same effect more easily than performing discharge with a time difference in the width direction, instead, the melt blow die itself is reciprocated in the width direction with respect to the conveyor, or the conveyor is moved in the width direction with respect to the die. A similar effect can be obtained by reciprocating.

The number of die spinnerets per unit length is an effective parameter in terms of improving the homogeneity of the nonwoven fabric in the planar direction and controlling the size of the internal space within a suitable range. In addition, the single-hole discharge rate and DCD can control the amount of nonwoven fabric applied per unit time and the thickness of the nonwoven fabric, respectively, and are effective in relatively controlling the internal space. In particular, when the single-hole discharge rate is reduced, the cooling of the fiber layer is promoted, and the internal space can be relatively enlarged. However, if it is too small, the resin becomes too thin and scatters without being collected on the conveyer (fly) phenomenon occurs, so it is desirable to adjust it within a certain range.
The amount of heated air can be adjusted to the average fiber diameter of the nonwoven fabric, and it is effective to increase the amount of air to obtain a constant leukocyte removal ability. However, if the temperature is too high, the fibers become too thin and scatter (fly) without being collected on the conveyer.

<Leukocyte removal method>
The leukocyte removal method includes, for example, the step of passing the leukocyte-containing fluid through a blood processing filter to remove leukocytes from the leukocyte-containing fluid.

Here, the leukocyte-containing fluid is a general term for body fluids and synthetic blood containing leukocytes. Consisting of whole blood and single or multiple types of blood components prepared from whole blood, such as plasma (PPP), platelet-rich plasma (PRP), plasma, frozen plasma, platelet concentrate and buffy coat (BC) It refers to liquids, solutions to which anticoagulants or preservatives are added, whole blood products, red blood cell products, platelet products, plasma products, and the like.
Further, a liquid obtained by treating the above liquid by the method of the present embodiment is referred to as a liquid from which leukocytes have been removed.

An embodiment of the method for removing leukocytes by the leukocyte removal method and preparing each blood product will be described below.

(Preparation of leukocyte-removed whole blood preparation)
Collected whole blood was added with Citrate Phosphate Dextrose (CPD), Citrate Phosphate Dextrose Adenine-1 (CPDA-1), Citrate Phosphate-2-Dextrose (CP2D), Acid Citrate Dextrose Formula-A ( ACD-A), Acid Citrate Dextrose Formula-B (ACD-B), a preservative solution such as heparin, a whole blood preparation added with an anticoagulant, etc. is prepared, and then leukocytes are removed from the whole blood preparation using the blood processing filter of the present embodiment. A leukocyte-removed whole blood preparation can be obtained thereby.

In the preparation of leukocyte-removed whole blood preparations, in the case of pre-storage leukocyte removal, whole blood is preferably stored at room temperature or under refrigeration within 72 hours after collection, more preferably within 24 hours, and particularly preferably within 12 hours. A leukocyte-depleted whole blood product can be obtained by removing leukocytes using a blood processing filter at room temperature or under refrigeration within 8 hours, most preferably within 8 hours. In the case of post-storage leukocyte depletion, leukocyte-removed whole blood preparations are prepared by removing leukocytes from whole blood stored at room temperature, under refrigeration or freezing, preferably within 24 hours before use using a blood processing filter. Obtainable.

(Preparation of leukocyte-removed red blood cell preparation)
CPD, CPDA-1, CP2D, ACD-A, ACD-B, preservatives such as heparin, and an anticoagulant are added to the collected whole blood. A method for separating each blood component is to remove leukocytes from whole blood and then perform centrifugation, or to remove leukocytes from red blood cells or red blood cells and BC after centrifuging whole blood.

When centrifugation is performed after removing leukocytes from whole blood, the leukocyte-removed red blood cell preparation can be obtained by centrifuging the leukocyte-removed whole blood.

When whole blood is centrifuged before leukocyte removal, there are two types of centrifugation conditions: weak centrifugation conditions for separating red blood cells and PRP, and strong centrifugation conditions for separating red blood cells, BC and PPP. If necessary, erythrocytes separated from whole blood or BC-containing erythrocytes are added with a storage solution such as SAGM, AS-1, AS-3, AS-5, MAP, etc., and then erythrocytes are removed using a leukocyte removal filter. A leukocyte-depleted red blood cell preparation can be obtained by removing leukocytes from the.

In the preparation of leukocyte-removed red blood cell preparations, whole blood that has been stored preferably at room temperature or under refrigeration is collected within 72 hours, more preferably within 48 hours, particularly preferably within 24 hours, and most preferably within 12 hours. Centrifugation can be performed.

In the case of pre-storage leukocyte depletion, preferably within 120 hours, more preferably within 72 hours, particularly preferably within 24 hours, most preferably within 12 hours after blood collection from red blood cell preparations stored at room temperature or under refrigeration. A leukocyte-depleted red blood cell preparation can be obtained by removing leukocytes using a blood processing filter under cold or refrigerated conditions. In the case of post-storage leukocyte depletion, the leukocyte-removed red blood cell preparation is preferably obtained by removing leukocytes from the red blood cell preparation stored at room temperature, under refrigeration or freezing, using a blood treatment filter within 24 hours before use. can be done.

(Preparation of leukocyte-removed platelet preparation)
CPD, CPDA-1, CP2D, ACD-A, ACD-B, preservatives such as heparin, and an anticoagulant are added to the collected whole blood.

As a method for separating each blood component, leukocytes are removed from whole blood and then centrifuged, and leukocytes are removed from PRP or platelets after whole blood is centrifuged.

When centrifugation is performed after removing leukocytes from whole blood, the leukocyte-free platelet preparation can be obtained by centrifuging the leukocyte-free whole blood.

When whole blood is centrifuged before leukocyte removal, there are two types of centrifugation conditions: weak centrifugation conditions for separating red blood cells and PRP, and strong centrifugation conditions for separating red blood cells, BC and PPP. In the case of weak centrifugation conditions, after removing leukocytes from PRP separated from whole blood with a blood processing filter and then centrifuging to obtain a leukocyte-removed platelet preparation, or after centrifuging PRP to obtain platelets and PPP, A leukocyte-free platelet preparation can be obtained by removing leukocytes with a blood processing filter. In the case of strong centrifugation conditions, one unit or several to ten-odd units of BC separated from whole blood is pooled, and if necessary, a storage solution, plasma, or the like is added and centrifuged to obtain platelets. A leukocyte-removed platelet preparation can be obtained by removing leukocytes from the obtained platelets with a blood processing filter.

In the preparation of a leukocyte-removed platelet preparation, whole blood that has been stored at room temperature is preferably centrifuged within 24 hours, more preferably within 12 hours, and particularly preferably within 8 hours after collection. In the case of pre-storage leukocyte removal, the platelet preparation stored at room temperature is preferably removed at room temperature within 120 hours, more preferably within 72 hours, particularly preferably within 24 hours, and most preferably within 12 hours after blood collection. A leukocyte-depleted platelet preparation can be obtained by removing leukocytes using a blood processing filter. In the case of post-storage leukocyte depletion, the leukocyte-removed platelet preparation is preferably obtained by removing leukocytes from the platelet preparation stored at room temperature, under refrigeration or freezing using a blood processing filter within 24 hours before use. can be done.

(Preparation of leukocyte-removed plasma preparation)
CPD, CPDA-1, CP2D, ACD-A, ACD-B, preservatives such as heparin, and an anticoagulant are added to the collected whole blood.

As a method for separating each blood component, leukocytes are removed from whole blood and then centrifuged, and leukocytes are removed from PPP or PRP after whole blood is centrifuged.

When centrifugation is performed after removing leukocytes from whole blood, the leukocyte-free plasma product can be obtained by centrifuging the leukocyte-free whole blood.

When whole blood is centrifuged before leukocyte removal, there are two types of centrifugation conditions: weak centrifugation conditions for separating red blood cells and PRP, and strong centrifugation conditions for separating red blood cells, BC and PPP. In the case of weak centrifugation conditions, leukocytes are removed from PRP with a blood processing filter and then centrifuged to obtain a leukocyte-removed plasma preparation, or PPP and platelets are centrifuged from PRP and then leukocytes are removed with a blood processing filter. A leukocyte-depleted plasma preparation can be obtained by In the case of strong centrifugation conditions, a leukocyte-free plasma product can be obtained by removing leukocytes from PPP with a blood processing filter.

In the preparation of leukocyte-removed plasma preparations, whole blood that has been stored preferably at room temperature or under refrigeration is collected within 72 hours, more preferably within 48 hours, particularly preferably within 24 hours, and most preferably within 12 hours. Centrifugation can be performed. Preferably within 120 hours, more preferably within 72 hours, particularly preferably within 24 hours, most preferably within 12 hours from the blood plasma preparation stored at room temperature or under refrigeration, blood at room temperature or under refrigeration A leukocyte-depleted plasma product can be obtained by removing leukocytes using a processing filter. In the case of post-storage leukocyte depletion, the leukocyte-removed plasma product is preferably obtained by removing leukocytes from the plasma product stored at room temperature, under refrigeration, or under freezing using a blood treatment filter within 24 hours before use. can be done.

As a form from blood collection to preparation of leukocyte-removed blood products, blood is collected with a blood collection needle connected to a container for whole blood, and a container containing whole blood or blood components after centrifugation is connected to a blood processing filter. Blood obtained by leukocyte removal, or blood obtained by at least a circuit in which a blood collection needle, a blood container, and a blood processing filter are aseptically connected, and subjected to leukocyte removal before or after centrifugation, or obtained by an automatic blood collection device Leukocyte removal may be performed in any form, such as connecting a blood processing filter to a container containing components or performing leukocyte removal with a blood processing filter pre-connected, but the present embodiment is not limited to these forms. do not have. In addition, after centrifuging the whole blood into each component with an automatic blood component collection device, adding a preservation solution as necessary, it is immediately transferred to a blood processing filter. A leukocyte-depleted red blood cell product or a leukocyte-depleted platelet product or a leukocyte-depleted plasma product may be obtained by removing leukocytes through any of

In this embodiment, leukocyte removal is performed by causing leukocyte-containing blood to flow from a container containing a leukocyte-containing liquid placed at a position higher than the blood processing filter to the blood processing filter via a tube due to a drop. Alternatively, the leukocyte-containing blood may be flowed by pressurizing the inlet side of the blood processing filter and/or decompressing it from the outlet side of the blood processing filter using means such as a pump.

EXAMPLES The present invention will be described below based on Examples, but the present invention is not limited to these. The performance of blood processing filters was measured by the following method.

(Evaluation of leukocyte removal ability/Evaluation of filtration time)
As the blood used for the evaluation, whole blood obtained by adding 56 mL of a CPD solution, which is an anticoagulant, to 400 mL of blood immediately after blood collection, mixing the mixture, and allowing the mixture to stand for 2 hours was used. Hereinafter, the blood prepared for this blood evaluation is referred to as unfiltered blood.
However, in the blood transfusion market, there are cases where blood stored at room temperature and blood stored in cold storage are used, so this time both cases were evaluated.

The blood bag filled with pre-filtered blood and the inlet of the blood treatment filter after steam heating were connected with a 40 cm vinyl chloride tube having an inner diameter of 3 mm and an outer diameter of 4.2 mm. Furthermore, the outlet of the blood processing filter and the collecting blood bag were connected with an 85 cm vinyl chloride tube having an inner diameter of 3 mm and an outer diameter of 4.2 mm. After that, the unfiltered blood is poured into the blood processing filter at a drop of 140 cm from the top of the blood bag filled with unfiltered blood, and the filtration time until the amount of blood flowing into the collection blood bag reaches 0.2 g/min. Measured.

Further, 3 mL of blood (hereinafter referred to as filtered blood) was collected from the collection blood bag. Leukocyte removal ability was evaluated by determining the number of residual leukocytes. The remaining leukocyte count was calculated according to the following formula by measuring the leukocyte count of blood after filtration using a flow cytometry method (device: FACSCanto manufactured by BECTON DICKINSON). The white blood cell count was measured by sampling 100 μL of each blood and using a Leucocount kit containing beads (Nippon Becton Dickinson Co., Ltd.).
Remaining white blood cell count = log [white blood cell concentration (cells/µL) (blood after filtration)] x blood volume (mL)

When carried out under the conditions of the above-mentioned filter shape (14 nonwoven fabrics, effective filtration area of 45 cm ² ), the number of residual white blood cells is less than 1×10 ⁶ in either blood stored at room temperature or refrigerated blood, and 45 If the completion of filtration can be achieved within minutes, it can be said to be a practically desirable leukocyte removal filter element. It is preferably within 40 minutes, more preferably within 35 minutes, even more preferably within 30 minutes. If the filtration time is short, more blood can be filtered per unit time in the limited space of the blood center, leading to improved work efficiency. In addition, if the filtration time is long, quality defects such as unexpected hemolysis may occur, leading to product disposal.
Serious side effects can be prevented when the residual white blood cell count is less than 1×10 ⁶ per bag (less than 6 Log/Bag). The fact that either blood stored at room temperature or blood stored refrigerated does not have to meet all requirements with one filter is not necessary, and if an appropriate filter is provided according to the usage environment, there is no practical problem. It is from. It is preferably 5.8 Log/Bag or less, more preferably 5.5 Log/Bag or less, still more preferably 5.3 Log or less. Since blood has large individual differences, it is known that the residual leukocyte count (logarithm) exhibits a normal distribution even with the same filter type, and the standard deviation is about 0.20 log. That is, if it is 5.8 Log or less, a 1σ variation (65%) can be considered to produce a safer blood product, 5.5 Log or less is 2σ, and 5.3 Log or less is 3σ variation. can be considered. In other words, with 5.3 Log, it is possible to prepare preparations considering a high blood compatibility rate of 99.7%, and it is possible to dramatically reduce the risk of transfusion side effects caused by the residual white blood cell count.

[Example 1]
(Preparation of filter layer)
A nonwoven fabric (fiber base material) was formed by spinning polybutylene terephthalate (PBT) by a meltblowing method. Here, the intrinsic viscosity of the PBT resin is 0.82 (dL/g), the single hole discharge amount is 0.21 (g/(min.hole)), and the pressure of the heated air during discharge is 0.30 (MPa). , the collecting conveyor speed was 4.1 (m/sec). The collection conveyor was circulated for 8.0 minutes to form a nonwoven on the conveyor. The die temperature during spinning was 280° C., and the distance between the nozzle and the collection conveyor was 6 cm.

The obtained fiber base material was coated with a hydrophilic polymer by the following method to obtain a nonwoven fabric having a coat layer (first filter layer). The hydrophilic polymer used contained no carboxyl groups, and the nonwoven fabric after coating had a carboxyl group equivalent of 122 μeq/g, the same as that of the fiber substrate.
A copolymer of 2-hydroxyethyl methacrylate (hereinafter abbreviated as HEMA) and diethylaminoethyl methacrylate (hereinafter abbreviated as DEAMA) was synthesized by conventional solution radical polymerization. A polymerization reaction was carried out at a monomer concentration of 1 mol/L in ethanol in the presence of 1/200 mol of azoisobutyronitrile (AIBN) as an initiator at 60° C. for 8 hours. A fibrous base material was immersed in an ethanol solution of the produced hydrophilic polymer. The fiber base material taken out of the polymer solution was squeezed to remove excess polymer solution absorbed, and the polymer solution was dried while blowing dry air to form a coating layer covering the surface of the fiber base material. .
The ratio of the amount of the basic nitrogen-containing functional group to the total amount of the nonionic group and the basic nitrogen-containing functional group in the peripheral surface portion (surface portion of the coat layer) of the obtained first filter layer is 3. 0 mol percent, and the mass of the coat layer in 1 g of the first filter layer was 1.5 mg/g (fiber base material + coat layer).
Various physical properties of the first filter layer are shown in Table 1.

(Preparation of blood processing filter)
14 sheets of the first filter layer are cut so that Am: Ac is 1.2: 1 (so that the direction of high orientation matches Am), and this is a soft filter with an effective filtration area of 45 cm ² A container was filled and ultrasonically welded to prepare a blood processing filter.
This blood treatment filter was subjected to steam heat treatment at 115° C. for 59 minutes and then vacuum dried at 40° C. for 15 hours or longer. The performance of the blood processing filter is shown in Table 1.

[Examples 2 to 10]
A nonwoven fabric (fiber base material) was prepared in the same manner as in Example 1 except that the intrinsic viscosity of the PBT resin, the single hole discharge amount, the speed of the collection conveyor, and the circulation time of the collection conveyor were changed as shown in Table 1. did.
Coating was performed in the same manner as in Example 1 to obtain a first filter layer. Various physical properties of the first filter layer are shown in Table 1.
As shown in Table 1, a blood processing filter was produced in the same manner as in Example 1, with the direction of the high degree of orientation coinciding with Am. The performance of the blood processing filter is shown in Table 1.

[Examples 11 to 20]
Examples 11-20 correspond to Examples 1-10, respectively. In Examples 11-20, the orientation of the first filter layer of Examples 1-10 was changed so that the direction of high degree of orientation coincided with Ac, as shown in Table 2. A blood processing filter was prepared in the same manner as in 10. The performance of the blood processing filter is shown in Table 2.
[Examples 21 to 30]
Examples 21-30 correspond to Examples 1-10, respectively. Examples 21-30 are blood treatment filters similar to Examples 1-10, except that the orientation of the first filter layer of Examples 1-10 is changed so that the Am:Ac ratio is 1:1. It was created. The performance of the blood processing filter is shown in Table 3. In Examples 21 to 30, blood having a higher viscosity and containing a relatively large amount of aggregates than the blood stored at room temperature used in Examples 1 to 20 was used.

[Comparative Example 1]
The intrinsic viscosity of the PBT resin is 0.85 (dL / g), the single hole discharge amount is 0.23 (g / (min.hole)), the pressure of the heated air during discharge is 0.32 (MPa), the collection A nonwoven fabric (fiber base material) was produced in the same manner as in Example 1, except that the conveyor speed was changed to 3.5 (m/sec) and the collection conveyor circulation time was changed to 7.3 minutes.
Coating was performed in the same manner as in Example 1 to obtain a filter layer. Various physical properties of the filter layer are shown in Table 4.
As shown in Table 4, a blood processing filter was produced in the same manner as in Example 1, with the direction of the high degree of orientation coinciding with Am. The performance of the blood processing filter is shown in Table 4.

[Comparative Example 2]
A blood processing filter was prepared in the same manner as in Comparative Example 1, except that the direction of the filter layer of Comparative Example 1 was changed so that the direction of the high degree of orientation coincided with Ac as shown in Table 4. The performance of the blood processing filter is shown in Table 4.

[Comparative Example 3]
The intrinsic viscosity of the PBT resin is 0.88 (dL / g), the single hole discharge amount is 0.25 (g / (min.hole)), the pressure of the heated air during discharge is 0.35 (MPa), the collection A nonwoven fabric (fiber base material) was produced in the same manner as in Example 1, except that the conveyor speed was changed to 3.2 (m/sec) and the collection conveyor circulation time was changed to 6.7 minutes.
Coating was performed in the same manner as in Example 1 to obtain a filter layer. Various physical properties of the filter layer are shown in Table 4. The degree of orientation of the nonwoven fabric of the filter layer of Comparative Example 3 was completely isotropic.
A blood treatment filter was prepared in the same manner as in Example 1. The performance of the blood processing filter is shown in Table 4.

[Comparative Example 4]
A blood treatment filter was prepared in the same manner as in Comparative Example 1, except that the direction of the filter layer of Comparative Example 1 was changed so that the Am:Ac ratio was 1:1. The performance of the blood processing filter is shown in Table 4. In Comparative Example 4, blood having a higher viscosity than the blood used in Comparative Example 1 and stored at room temperature and containing a relatively large amount of aggregates was used.

[Comparative Example 5]
The performance of the blood processing filter of Comparative Example 3 was evaluated using blood that was more viscous than the room temperature stored blood used in Comparative Example 3 and contained relatively more aggregates. The results are shown in Table 4.

From the results of Examples 1 to 30 and Comparative Examples 1 to 5, the maximum orientation ratio of the nonwoven fabric was set to 1.2 or more, and the ratio of Am and Ac was appropriately adjusted according to the properties of blood. Better filtration times or white blood cell counts can be achieved compared to using the comparative nonwoven fabric, which is more isotropic.

In particular, from the results of Examples 21 to 30, the nonwoven fabric having a maximum orientation ratio of 1.2 or more can filter highly viscous blood in a short time even if Am:Ac is 1:1, and residual leukocytes It has been found that the number can be reduced. This suggests that when the orientation ratio of the nonwoven fabric is high, blood flow channels are formed, and even blood with high viscosity maintains a steady flow rate without causing clogging, and as a result, the filtration time is shortened. . In addition, by preventing clogging of the flow path, the effective utilization of the filter medium is improved, and the number of residual white blood cells, which is originally in a trade-off relationship, is also improved compared to Comparative Example 4 (existing product). Indicated.

Furthermore, in Examples 2 to 9, the residual leukocyte count was 5.5 log or less and the filtration time was 40 minutes or less in cold hemofiltration, and the improvement of the preparation quality and the workability accompanying the improvement of the leukocyte removal ability were observed. . In particular, in Examples 2 to 6, the residual leukocyte count was 5.3 log or less, and the leukocyte removal ability was further improved.

Furthermore, in Examples 12 to 19, the number of residual leukocytes in room temperature hemofiltration was 5.8 log or less, and the filtration time was 40 minutes or less, and improvement in preparation quality and workability accompanied by improvement in leukocyte removal ability was observed. . In particular, in Examples 12 to 16, the filtration time was 35 minutes or less, and the working efficiency was further improved.

Furthermore, in Examples 22 to 29, the residual leukocyte count was 5.5 log or less, and the filtration time was 40 minutes or less, indicating an improvement in formulation quality and workability associated with an improvement in leukocyte removal ability. In addition, in Examples 22 to 27, the filtration time was 30 minutes or less, further improving the working efficiency. Particularly, in Examples 22 to 25, the residual leukocyte count was 5.3 log or less, and the leukocyte removing ability was further improved.

From the above results, the nonwoven fabric with a maximum orientation ratio of 1.28 to 2.0 has improved filtration performance, and the nonwoven fabric with a maximum orientation ratio of 1.28 to 1.42 has further improved performance. Ta.

Next, using an existing leukocyte-removing filter or a filter layer prepared based on the manufacturing method described in a known document, we decided to compare performance by whole blood filtration.

[Example 31]
(Preparation of blood treatment filter)
The 14 sheets of the first filter layer used in Example 1 were cut into 3 cm squares so that the ratio of Am:Ac was 1.2:1 (the direction of the high degree of orientation coincided with Am). was filled into a flexible container having an effective filtration area of 9 cm ² and ultrasonically welded to prepare a blood processing filter. This is because known filters have various sizes, and in order to carry out tests with the same size, only small filters can be used for relative evaluation.
This blood treatment filter was subjected to steam heat treatment at 115° C. for 59 minutes and then vacuum dried at 40° C. for 15 hours or longer. The performance of the blood processing filter is shown in Table 5.

(Evaluation of leukocyte removal ability/Evaluation of filtration time)
As the blood used for the evaluation, whole blood obtained by adding 11.2 mL of a CPD solution, which is an anticoagulant, to 80 mL of blood immediately after blood collection, mixing the mixture, and allowing it to stand for 2 hours was used. Hereinafter, the blood prepared for this blood evaluation is referred to as unfiltered blood.
However, in the blood transfusion market, there are cases where blood stored at room temperature and blood stored in cold storage are used, so this time both cases were evaluated.

The blood bag filled with pre-filtered blood and the inlet of the blood treatment filter after steam heating were connected with a 40 cm vinyl chloride tube having an inner diameter of 3 mm and an outer diameter of 4.2 mm. Furthermore, the outlet of the blood processing filter and the collecting blood bag were connected with an 85 cm vinyl chloride tube having an inner diameter of 3 mm and an outer diameter of 4.2 mm. After that, the unfiltered blood is poured into the blood processing filter at a drop of 140 cm from the top of the blood bag filled with unfiltered blood, and the filtration time until the amount of blood flowing into the collection blood bag reaches 0.2 g/min. Measured.

Further, 3 mL of blood (hereinafter referred to as filtered blood) was collected from the collection blood bag. Leukocyte removal ability was evaluated by determining the number of residual leukocytes. The method for measuring the residual white blood cell count is as described above.

When carried out under the conditions of the filter shape (14 non-woven fabrics, effective filtration area of 9 cm ² ), the residual leukocyte count is less than 5.3 Log/Bag in either room-temperature-stored blood or refrigerated-stored blood, and 45 If the completion of filtration can be achieved within minutes, it can be said to be a practically desirable leukocyte removal filter element.
The residual white blood cell count is preferably 5.12 Log/Bag or less, more preferably 4.95 Log/Bag or less, still more preferably 4.77 Log/Bag or less. The filtration time is preferably 40 minutes or less, more preferably 35 minutes or less, still more preferably 30 minutes or less.
This filtration time value is the same as for the normal filter size described in Examples 1-30. This is because the effective filtration area is 1/5 that of a normal filter, and the amount of filtered blood is also 1/5, so the amount of blood flowing through the filter medium per unit area is the same in both cases. Therefore, the filtration time can be defined in the same time as in the case of ordinary filters.
However, since the residual white blood cell count is 1/5 of the blood volume, the standard is less than 0.2×10 ⁶ per bag (less than 5.3 Log/Bag), and the standard deviation is about 0.18 Log. , the preferred performance values change. Table 5 shows the performance test results of the small blood processing filter.

[Comparative Examples 6 and 7]
Haemonetics eWBF3J was disassembled, and a relatively fine filter layer with an average fiber diameter of 1.6 to 1.8 μm was collected. However, since the basis weight of the nonwoven fabric was 88 g/m ² , 15 nonwoven fabrics were laminated and used in order to equalize the weight of the nonwoven fabrics used for the filter.
Since the maximum orientation ratio was 1.65, the films were laminated on filters so that Am:Ac = 1.65:1 and 1:1.65, and evaluated respectively. Table 5 shows the test results.

[Comparative Examples 8 and 9]
RZ-2000F manufactured by Asahi Kasei Medical Co., Ltd. was dismantled, and a fine filter layer with an average fiber diameter of 1.3 μm was collected. However, since the basis weight of the nonwoven fabric was 40 g/m ² , 32 nonwoven fabrics were laminated and used.
Since the maximum orientation ratio was 1.13, they were laminated on filters so that Am:Ac = 1.13:1 and 1:1.13, and evaluated respectively. Table 5 shows the test results.

[Comparative Examples 10 to 13]
The leukocyte removal filter included in the Compoflow system manufactured by Fresenius Kabi was dismantled, and two types of filter layers with a small average fiber diameter and different bulk densities were collected. Hemofiltration with a small filter was performed in the method. However, since the fabric weights of the nonwoven fabrics were 55 g/m ² and 53 g/m ² , respectively, 23 and 24 nonwoven fabrics were laminated and used. Table 5 shows the test results. Nonwoven fabrics with a basis weight of 55 g/m ² are described in Comparative Examples 10 and 11, and nonwoven fabrics with a basis weight of 53 g/m ² are described in Comparative Examples 12 and 13.

[Comparative Examples 14 and 15]
A nonwoven fabric described in Example 60 of PCT International Publication H10-508343 was produced. However, as manufacturing conditions not described in this example, the resin viscosity is 0.82 g / dL, the distance between the centers of each nozzle is 0.1 cm, the nozzles are arranged in one row with 200 nozzles, and the inclination angle of the nozzles is 0 degrees. As a result, a nonwoven fabric having the physical properties described in Examples was obtained, and blood filtration using a small filter was performed in the same manner as in Example 31 of the present application. Since the fabric weight of the nonwoven fabric is 54 g/m ² , 24 nonwoven fabrics were laminated and used. Table 5 shows the test results.

[Comparative Examples 16 and 17]
Using the PBT nonwoven fabric described in Example 1 of International Publication No. 2018/034213, blood filtration with a small filter was performed in the same manner as in Example 31 of the present application. Since the fabric weight of the nonwoven fabric is 22 g/m ² , 59 nonwoven fabrics were laminated and used. Table 5 shows the test results.

Next, using an erythrocyte preparation, which has a higher viscosity than whole blood and whose filtration time can be detected more accurately, the effect of forming an internal space in the nonwoven fabric was confirmed in the following tests.

(Leukocyte removal performance of blood processing filter)
As a blood product, 300 g of erythrocyte preparation prepared according to the European standard (the Guide to the Preparation, Use and Quality Assurance of Blood Components 19th edition (2017)) was used, and this was used with a free fall of 110 cm in Examples and Comparative Examples. was filtered and collected using a blood processing filter of No. 1 to obtain a post-filtration blood product. Here, the drop is from the bottom of the pre-filtration bag containing the red blood cell product to the bottom of the post-filtration collection bag of the red blood cell product (the top plate of the balance in the example of FIG. 7).
Then, the residual leukocyte count was calculated according to the following formula.
Remaining leukocyte count = log [(leukocyte concentration in post-filtration blood product) x (post-filtration blood recovery volume)]
The leukocyte concentration in the blood preparation before and after filtration was measured using a leukocyte count measurement kit "LeucoCOUNT" manufactured by Becton Deckinson (BD) and a flow cytometer FACS Canto II manufactured by BD.

[Evaluation Criteria for Remaining White Blood Cell Count]
◎: Less than 5.0 ○: 5.0 or more and less than 5.5 ×: 5.5 or more Serious side effects can be prevented when the residual white blood cell count is less than 1×10 ⁶ per bag (less than 6 log/bag). The possible points are the same as whole blood. However, in addition to individual differences in the original whole blood, red blood cell preparations are known to have large differences due to blood properties due to variations in the preparation of red blood cell preparations. The normal distribution has a standard deviation of about 0.30 Log. In other words, if it is less than 5.0 Log, it is possible to prepare a preparation considering a high blood compatibility rate of 99.7% or more, and it is possible to dramatically reduce the risk of transfusion side effects caused by the residual white blood cell count. It becomes possible. On the other hand, if it is less than 5.5 Log, the matching rate is 90%, so it can be used practically.

(filtration time)
In the above "(Leukocyte removal performance of blood processing filter)", the time (minutes) required from the start of flowing red blood cell products through the blood processing filter until the mass of the collection bag of red blood cell products after filtration stops increasing is defined as the filtration time (minutes). ). The stop of the increase in the mass of the collection bag refers to the time when the mass of the collection bag is measured every minute from the start of filtration and the change in the mass of the collection bag is 0.1 g/min or less. The final 1 minute, which was determined as the end of the mass increase, was included in the calculation of the filtration time.
[Evaluation criteria]
◎: Less than 20 minutes ○: 20 minutes or more and less than 26 minutes ×: 26 minutes or more Should be less than 26 minutes. Furthermore, it is more preferably less than 20 minutes.

(Blood loss rate)
The collection was terminated when the change in the weight of the collection bag for 1 minute was 0.1 g or less, and the value on the balance at the end of the collection was defined as the amount of collected blood. Also, the blood loss rate was obtained from the following formula.
Blood loss rate (%) = 100 (%) × ((pre-filtration blood volume (g) - blood recovery volume (g)) / pre-filtration blood volume (g)
[Evaluation criteria]
◎: less than 8.0% ○: 8.0% or more and less than 9.2% ×: 9.2% or more Since there are individual differences, the amount of blood collected must be calculated in terms of the loss rate. Based on the results of the existing leukocyte removal filter (Asahi Kasei Medical R-S11 red blood cell product filter), the blood loss rate should be less than 9.2% in practice. Furthermore, it is more preferably less than 8.0%. By doing so, the loss of useful blood can be reduced. As a result, the number of preparation bags to be administered to the same patient at the time of blood transfusion can be reduced, leading to cost reduction and work efficiency at medical institutions.

[Example A1]
(Preparation of filter layer)
Polybutylene terephthalate (PBT) was spun by a meltblowing method to form a nonwoven fabric (fiber base material). A rotating conveyor type device was used for collection. Ten melt blow dies having a spinneret number of 10 holes/cm and a die length (0.20 m) one-tenth the collection width (2 m) of the collection conveyor were arranged. A method of spinning with a time lag from the end in the width direction was adopted. The single-hole discharge amount was 0.17 (g/(min.hole)), the collection conveyor rotation speed was 220 m/min, the switching time for each spinneret was 4.1 seconds, and the discharge movement speed was 0.07 m/second. and Further, the distance (DCD) between the melt blow die and the collection conveyor was adjusted to 50 mm. The die temperature during spinning was set at 280°C.

The obtained nonwoven fabric was coated with a hydrophilic polymer by the following method to obtain a nonwoven fabric having a coat layer (first filter layer). After immersing the nonwoven fabric in an ethanol solution of a hydrophilic polymer (concentration: 1.5 g/L), the nonwoven fabric taken out of the polymer solution was squeezed to remove the excess polymer solution that was absorbed, while sending dry air. The polymer solution was dried to form a coat layer covering the outer peripheral surface of the nonwoven fabric.
The ratio of the amount of the basic nitrogen-containing functional group to the total amount of the nonionic group and the basic nitrogen-containing functional group in the peripheral surface portion (surface portion of the coat layer) of the obtained first filter layer is 3. 0 mol percent, and the mass of the coat layer in 1 g of the first filter layer was 3 mg/g (fiber base material + coat layer).
Various physical properties of the first filter layer are shown in Table 6. FIG. 9 shows the variation of the in-plane porosity in the thickness direction of the first filter layer.

(Preparation of blood treatment filter)
As the second filter layer and the third filter layer, polyethylene terephthalate (hereinafter referred to as "PET") having a basis weight of 30 (g/m ² ) and airflow resistance per unit basis weight of 0.03 (kPa·s·m/g) abbreviated) was used.
Four second filter layers, 16 first filter layers, and four third filter layers were laminated in order from upstream to downstream of the blood flow. This laminate is sandwiched between two flexible vinyl chloride resin sheets having a port serving as an inlet or outlet for blood, and a high-frequency welding machine is used to weld the filter material and the peripheral edge of the flexible sheet. , were integrated to produce a blood processing filter with an effective filtration area of 43 cm ² . The blood treatment filter was subjected to autoclave sterilization at 115° C. for 59 minutes, and then tested for various performances. Table 6 shows the results.

[Example A2]
Example A1 except that the spinning width was changed to 1.6 m, eight spinnerets were arranged in the width direction, and the discharge movement speed was changed to 0.08 to 0.09 m/sec by adjusting the spinneret switching time. A first filter layer and a blood treatment filter were prepared in the same manner as above. Table 6 shows the physical properties of the first filter layer and the performance of the blood processing filter.

[Example A3]
Example A1 except that the spinning width was changed to 1.8 m, nine spinnerets were arranged in the width direction, and the discharge movement speed was changed to 0.07 to 0.08 m/sec by adjusting the spinneret switching time. A first filter layer and a blood treatment filter were prepared in the same manner as above. Table 6 shows the physical properties of the first filter layer and the performance of the blood processing filter.

[Example A4]
In the same manner as in Example A1, except that the spinning head switching time was adjusted to change the discharge moving speed to 0.06 to 0.07 m / sec, and a residence time of 15 seconds was provided when the discharge area turned back. A filter layer and blood processing filter were made. Table 6 shows the physical properties of the first filter layer and the performance of the blood processing filter.

[Example A5]
Adjust the spinneret switching time to change the discharge movement speed to 0.09m/sec, change the collection conveyor rotation speed to 225-230m/min, change the melt blow die length to 0.40m, and change the spinneret in the width direction. A first filter layer and a blood processing filter were prepared in the same manner as in Example A1, except that five units were arranged. Table 6 shows the physical properties of the first filter layer and the performance of the blood processing filter.

[Examples A6 to A8]
The collection conveyor rotation speed was changed to 223 to 228 m / min in Example A6, changed to 220 to 225 m / min in Example A7, and changed to 215 to 220 m / min in Example A8. A first filter layer and a blood processing filter were similarly prepared. Table 6 shows the physical properties of the first filter layer and the performance of the blood processing filter.

[Example A9]
Example A1, except that the spinneret switching time was adjusted to change the discharge movement speed to 0.08 to 0.09 m/sec, the melt blow die length was changed to 0.40 m, and five spinnerets were arranged in the width direction. A first filter layer and a blood treatment filter were prepared in the same manner as above. Table 6 shows the physical properties of the first filter layer and the performance of the blood processing filter.

[Example A10]
The first filter layer and the blood treatment filter were formed in the same manner as in Example A1, except that the spinneret switching time was adjusted to change the discharge movement speed to 0.07 to 0.08 m/sec and the DCD to 48 to 50 mm. Created. Table 6 shows the physical properties of the first filter layer and the performance of the blood processing filter.

[Example A11]
The first filter layer and the blood treatment filter were formed in the same manner as in Example A1, except that the spinneret switching time was adjusted to change the discharge movement speed to 0.06 to 0.07 m/sec and the DCD to 46 to 48 mm. Created. Table 6 shows the physical properties of the first filter layer and the performance of the blood processing filter.

[Example A12]
A first filter layer and a blood treatment filter were prepared in the same manner as in Example A1, except that the rotation speed of the collecting conveyor was changed to 220-225 m/min and the DCD was changed to 58-60 mm. Table 6 shows the physical properties of the first filter layer and the performance of the blood processing filter. FIG. 10 shows the variation of the in-plane porosity in the thickness direction of the first filter layer.
[Example A13]
Adjust the spinneret switching time to change the discharge moving speed to 0.06 to 0.07 m / sec, change the collecting conveyor rotation speed to 220 to 225 m / min, change the DCD to 55 to 60 mm, and change the melt blow die length. A first filter layer and a blood treatment filter were prepared in the same manner as in Example A1, except that the length was changed to 0.153 m and 13 spinnerets were arranged in the width direction. Table 6 shows the physical properties of the first filter layer and the performance of the blood processing filter.

[Example A14]
Adjust the spinning head switching time to change the discharge moving speed to 0.06 to 0.07 m / sec, change the collecting conveyor rotation speed to 225 to 230 m / min, change the DCD to 60 to 65 mm, and change the melt blow die length. A first filter layer and a blood treatment filter were prepared in the same manner as in Example A1, except that the length was changed to 0.153 m and 13 spinnerets were arranged in the width direction. Table 6 shows the physical properties of the first filter layer and the performance of the blood processing filter.

[Examples A15 and A16]
The spinning head switching time was adjusted to change the discharge moving speed to 0.06 to 0.07 m/sec, and the collection conveyor rotation speed was changed to 225 to 228 m/min in Example A15, and 220 to 225 m in Example A16. A first filter layer and a blood treatment filter were prepared in the same manner as in Example A1, except that the flow rate was changed to /min. Table 7 shows the physical properties of the first filter layer and the performance of the blood treatment filter.

[Example A17]
A first filter layer and a blood treatment filter were prepared in the same manner as in Example A1, except that the spinneret switching time was adjusted to change the discharge movement speed to 0.06 to 0.07 m/sec. Table 7 shows the physical properties of the first filter layer and the performance of the blood treatment filter.

[Examples A18 and A19]
The DCD was changed from 55 to 60 mm in Example A18 and from 40 to 45 mm in Example A19, and the single hole discharge rate was changed from 0.28 g/min/hole in Example A18 to 0 in Example A19. A first filter layer and a blood processing filter were prepared in the same manner as in Example A1 except that the flow rate was changed to .18 g/min/hole. Table 7 shows the physical properties of the first filter layer and the performance of the blood treatment filter.

[Examples A20 to A22]
The procedure was carried out except that the concentration of the hydrophilic polymer solution in the coating was changed to 0.3 g/L for Example A20, 1.0 g/L for Example A21, and 5.0 g/L for Example A22. A first filter layer and a blood treatment filter were prepared as in Example A1. Table 7 shows the physical properties of the first filter layer and the performance of the blood treatment filter.

[Examples A23 and A24]
A first filter layer and a blood treatment filter were prepared in the same manner as in Example A1 except that the DCD was changed from 55 to 60 mm in Example A23 and from 45 to 50 mm in Example A24. The nonwoven fabric (fiber base material) was pressed with a weak pressure in Example A23, and was pressed with a strong pressure in Example A24 to adjust the filling rate. Table 7 shows the physical properties of the first filter layer and the performance of the blood treatment filter.

[Comparative Example A1]
A first filter layer and a blood treatment filter were prepared in the same manner as in Example A1, except that the length of the meltblowing die was changed to 0.3 m, the spinning width was changed to 0.3 m, and discharge was not performed with a time lag. Table 7 shows the physical properties of the first filter layer and the performance of the blood treatment filter. FIG. 11 shows the variation of the in-plane porosity in the thickness direction of the first filter layer.

[Comparative Example A2]
A first filter layer and a blood treatment filter were prepared in the same manner as in Comparative Example A1, except that the single hole discharge rate was changed to 0.24 g/min/hole. Table 7 shows the physical properties of the first filter layer and the performance of the blood treatment filter. FIG. 12 shows the variation of the in-plane porosity in the thickness direction of the first filter layer.

[Comparative Example A3]
A first filter layer and a blood treatment filter were prepared in the same manner as in Comparative Example A1, except that the discharge rate per hole was changed to 0.23 g/min/hole and the DCD was changed to 45-50 mm. Table 7 shows the physical properties of the first filter layer and the performance of the blood treatment filter.

[Comparative Example A4]
A non-rotating belt conveyor net was used as a collecting device, and spinning was performed while sucking the yarn under the net. PET resin is used, the single hole discharge rate is adjusted to 0.08 g/min/hole, DCD is adjusted to 50 mm, the melt blow die length is 0.3 m, the spinning width is 0.3 m, and the belt conveyor movement speed is 0.05 m/ Seconds, a nonwoven fabric was formed by a method in which ejection was not performed with a time difference. The obtained nonwoven fabric was coated with a hydrophilic polymer in the same manner as in Example A1 to prepare a first filter layer. Various physical properties of the first filter layer are shown in Table 7.
Using the obtained first filter layer, a blood processing filter was produced in the same manner as in Example A1. Various performances of the blood processing filter are shown in Table 7.

By making a filter using a non-woven fabric whose maximum orientation ratio is controlled to a certain level or more, or by using a filter layer with a predetermined space inside, the blood filtration time is shortened and the number of residual white blood cells is also reduced. You can get the effect you can. This is considered to have industrial applicability because it improves the quality of blood in the transfusion market, shortens the time required for formulation preparation at the manufacturing site, and improves productivity.

DESCRIPTION OF SYMBOLS 1... Container, 3... Inlet part, 4... Outlet part, 5... Filter material, 7... Inlet part side space, 8... Outlet part side space, 9... Outer edge part of filter material, 10... Blood processing filter, 11... First filter Layer 12... Filtration direction 13... Planar direction perpendicular to the filtration direction 14... Planar direction parallel to the filtration direction 15... Blood flow (inlet part) 16... Blood flow (outlet part) 17... Planar direction Maximum length, 18 ... Maximum length in the thickness direction

Claims (14)

a container having an inlet and an outlet for blood;
a filter medium disposed within the container between the inlet and the outlet;
A blood processing filter comprising:
the filter medium comprises a filter layer,
the filter layer comprises a non-woven fabric,
The fibers of the nonwoven fabric have an orientation degree X in the X-axis plane direction of the filter layer and an orientation degree Y in the Y-axis plane direction orthogonal to the X-axis plane direction,
The maximum value of the ratio of the orientation degree X to the orientation degree Y (orientation degree X/orientation degree Y) is 1.2 or more.
Said blood processing filter. 2. The blood processing filter according to claim 1, wherein the maximum value of orientation degree X/orientation degree Y is 1.4 or more. The ratio (Ac /Am) is 1.2 or more, the blood processing filter according to claim 1 or 2, wherein the filter layer is arranged. 4. The blood processing filter according to claim 3, wherein Ac/Am is 1.4 or more. The ratio ( Am 3. The blood processing filter according to claim 1 or 2, wherein the filter layer is arranged such that /Ac) is 1.2 or more. 6. The blood processing filter according to claim 5, wherein Am/Ac is 1.4 or more. The blood processing filter according to any one of claims 1 to 6, wherein said nonwoven fabric is a polyester nonwoven fabric. a container having an inlet and an outlet for blood;
a filter medium disposed within the container between the inlet and the outlet;
A blood processing filter comprising:
the filter medium comprises one or more filter layers;
The filter layer has a space with a maximum planar length of 50 μm or more and a maximum thickness of 15 μm or more and 150 μm or less in a cross section in the thickness direction.
Said blood processing filter. The blood processing filter according to claim 8, wherein the filter layer has a filling factor of 0.09 to 0.26. 10. The blood processing filter according to claim 8, wherein the difference between the minimum in-plane porosity in the thickness direction and the maximum in-plane porosity in the thickness direction of the filter layer is 0.08 to 0.28. 11. The blood processing filter according to claim 10, wherein the minimum in-plane porosity in the thickness direction is 0.72 to 0.85, and the maximum in-plane porosity in the thickness direction is 0.85 to 1.00. A blood processing filter according to any one of claims 8 to 11, wherein the filter layer has a specific surface area of 0.50 to 1.50 m ² /g. A blood processing filter according to any one of claims 8 to 12, wherein said filter layer has a critical wetting surface tension of 70 to 100 dyn/cm. A method for producing a blood product, comprising the step of passing blood containing leukocytes through the blood processing filter according to any one of claims 1 to 13.