Blood processing filter and method for producing blood preparation

Abstract

The object is to provide a blood processing filter having excellent leukocyte removal rate and filtration time (filtration speed). The aforementioned problems can be solved by the following blood filter. A blood processing filter, comprising: a container having an inlet and an outlet for blood, and a filter material arranged between the inlet and the outlet in the aforementioned container, the aforementioned filter material comprising a filter layer, the aforementioned filter layer comprising a non-woven fabric, the fibers of the aforementioned non-woven fabric having an orientation degree X in the X-axis plane direction of the aforementioned filter layer, and an orientation degree Y in the Y-axis plane direction orthogonal to the aforementioned X-axis plane direction, and the maximum value of the ratio of the aforementioned orientation degree X to the aforementioned orientation degree Y (orientation degree X / orientation degree Y) is greater than 1.2.

Description

Technical Field

[0001] The present invention relates to a blood processing filter and a method for producing a blood preparation. Background Art

[0002] In the field of blood transfusion, in addition to so-called whole blood transfusion, which is to transfuse a whole blood preparation obtained by adding an anticoagulant to blood collected from a blood donor, so-called component transfusion, which is to separate the blood components required by the recipient from the whole blood preparation and transfuse the blood components, is generally performed. Component transfusion includes red blood cell transfusion, platelet transfusion, plasma transfusion, etc. depending on the type of blood components required by the recipient, and the blood preparations used in these transfusions include red blood cell preparations, platelet preparations, plasma preparations, etc.

[0003] In addition, so-called leukocyte-depleted transfusion, which removes the leukocytes contained in blood products and then delivers the blood products, has recently become popular. This is because it is known that relatively minor side effects associated with transfusion, such as headache, nausea, chills, and non-hemolytic fever, as well as serious side effects such as alloantigen sensitization, viral infection, and post-transfusion GVHD that have serious effects on the recipient, are mainly caused by leukocytes mixed in the blood products used for transfusion. In order to prevent relatively minor side effects such as headache, nausea, chills, and fever, it is said that the leukocytes in blood products are removed to a residual rate of 10%. -1 ~10 -2 In order to prevent alloantigen sensitization and viral infection, which are serious side effects, it is said that it is necessary to remove white blood cells to a residual rate of 10 -4 ~10 -6 the following.

[0004] In recent years, leukocyte removal therapy using extracorporeal circulation of blood has been used to treat rheumatism, ulcerative colitis, and the like, and has achieved high clinical effects.

[0005] There are two main methods for removing leukocytes from blood products: centrifugal separation using a centrifuge to separate and remove leukocytes by utilizing the specific gravity difference of blood components; and filter method using a filter element including a fiber assembly such as a nonwoven fabric or a porous structure having continuous pores to remove leukocytes. The filter method that removes leukocytes by adhesion or adsorption is the most popular at present because of its advantages such as simple operation and low cost.

[0006] In recent years, new requirements have been put forward for leukocyte removal filters in medical fields. One of the requirements is to further miniaturize and lighten the filters in order to reduce the disposal cost of the filters. The reason is that the filters after filtering blood are equivalent to infectious waste, and the disposal cost is usually incurred according to the unit price per unit weight. By miniaturization, unnecessary costs can be further reduced for medical institutions.

[0007] In this case, the idea of ​​effective filter design is to improve the effective utilization rate of the filter material used in the filter. By improving the effective utilization rate, even a small amount of filter material can adsorb a sufficient amount of white blood cells in the blood. As a means for this, the following method is often used: when blood flows into the filter, the filter material is evenly distributed in the direction extending perpendicularly to the blood flow (usually the plane direction of the filter), so that the blood is evenly extended into the filter, resulting in an improved effective utilization rate.

[0008] As a specific example, Patent Document 1 discloses that the leukocyte removal rate of a filter material is improved by using a nonwoven fabric as a kind of filter material and improving the uniformity in the plane direction (making the texture good).

[0009] Patent Document 2 discloses a technique for achieving both improvement in leukocyte removal efficiency and shortening of filtration time by appropriately controlling the flow rate (permeation coefficient) of blood in the plane direction and vertical direction of a filter.

[0010] Prior art literature

[0011] Patent Literature

[0012] Patent Document 1: International Publication No. 2004 / 050146

[0013] Patent Document 2: International Publication No. 2005 / 120600 Summary of the invention

[0014] Problem that the invention aims to solve

[0015] It was found that when using the filter material of Patent Document 1 in which nonwoven fibers are evenly distributed, the aggregates contained in the blood uniformly clog the surface of the nonwoven fabric, and the risk of blood being discarded due to prolonged filtration time and filtration stop is high, making it unsuitable for filtration. It was also found that blood with low viscosity will pass through the filter immediately, so the residence time in the filter is too short, and the leukocyte removal rate is low. In other words, there is the following problem: only specific blood with appropriate viscosity and as little aggregates as possible that induce clogging can be filtered.

[0016] Patent Document 2 does not specifically define the anisotropy of the flow in the plane, so it does not consider how to control the flow in the plane and make effective use of it. As a result, a biased flow occurs in the plane, and the filtering performance cannot be fully utilized. In other words, due to the uneven flow in the plane, low-viscosity blood only passes through a part of the filter area, and the entire filter is not utilized, so the filtering performance is insufficient, and there is a problem that the filter design needs to be changed due to the properties of the blood.

[0017] An object of the present invention is to provide a blood processing filter having excellent leukocyte removal rate and filtration time (filtration speed).

[0018] Solutions for solving problems

[0019] The inventors etc. have repeatedly studied deeply, and found that, by adjusting the direction of the fiber of the nonwoven fabric contained in the filtration layer constituting the filter material, thus can solve the aforementioned problems.In addition, the inventors etc. have found that, by arranging the space of regulation in the inside of the filtration layer constituting the filter material, also can solve the aforementioned problems.

[0020] That is, the present invention is as follows.

[0021] [1] A blood processing filter comprising:

[0022] a container having an inlet and an outlet for blood, and

[0023] The filter material disposed between the inlet and the outlet in the container,

[0024] The aforementioned filter material comprises a filter layer,

[0025] The aforementioned filter layer comprises nonwoven fabric,

[0026] 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.

[0027] 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.

[0028] [2] The blood processing filter according to [1], wherein the maximum value of the orientation degree X / orientation degree Y is 1.4 or more.

[0029] [3] A blood processing filter according to [1] or [2], wherein the filter layer is arranged in such a manner that a ratio (Ac / Am) of the orientation degree (Ac) of the fibers in a planar direction of the filter layer orthogonal to the filtering direction to the orientation degree (Am) of the fibers in a planar direction of the filter layer parallel to the filtering direction is greater than 1.2.

[0030] [4] The blood processing filter according to [3], wherein Ac / Am is 1.4 or more.

[0031] [5] A blood processing filter according to [1] or [2], wherein the filter layer is arranged in such a manner that a ratio (Am / Ac) of the degree of orientation (Am) of the fibers in a planar direction of the filter layer parallel to the filtering direction to the degree of orientation (Ac) of the fibers in a planar direction of the filter layer orthogonal to the filtering direction is greater than 1.2.

[0032] [6] The blood processing filter according to [5], wherein Am / Ac is 1.4 or more.

[0033] [7] The blood processing filter according to any one of [1] to [6], wherein the nonwoven fabric is a polyester nonwoven fabric.

[0034] [8] A blood processing filter comprising:

[0035] a container having an inlet and an outlet for blood, and

[0036] The filter material disposed between the inlet and the outlet in the container,

[0037] The aforementioned filter material comprises more than one filter layer.

[0038] The filter layer has, in a cross section in the thickness direction, a space having a maximum length in the planar direction of 50 μm or more and a maximum length in the thickness direction of 15 μm or more.

[0039] [9] The blood processing filter according to [8], wherein the filling rate of the filter layer is 0.09 to 0.26.

[0040]

[10] The blood processing filter according to [8] or [9], wherein the difference between the minimum porosity in a plane in the thickness direction and the maximum porosity in a plane in the thickness direction of the filter layer is 0.08 to 0.28.

[0041]

[11] The blood processing filter according to

[10] , wherein the minimum porosity in the plane in the thickness direction is 0.72 to 0.85, and the maximum porosity in the plane in the thickness direction is 0.85 to 1.00.

[0042]

[12] The blood processing filter according to any one of [8] to

[11] , wherein the specific surface area of ​​the filter layer is 0.50 to 1.50 m 2 / g.

[0043]

[13] The blood processing filter according to any one of [8] to

[12] , wherein the critical wetting surface tension of the filter layer is 70 to 100 dyn / cm.

[0044]

[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] .

[0045] Effects of the Invention

[0046] According to the present invention, a blood processing filter having excellent leukocyte removal rate and filtration time (filtration speed) can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 This is a schematic diagram of a blood processing filter as one embodiment of the present invention.

[0048] Figure 2 for Figure 1 Cross-sectional view of a blood processing filter.

[0049] Figure 3 This is a schematic diagram of a blood processing filter as one embodiment of the present invention.

[0050] Figure 4 To observe from the front Figure 3 Schematic diagram of a plan view of a blood processing filter.

[0051] Figure 5 It is a diagram showing the method of adjusting Ac:Am.

[0052] Figure 6 It is a diagram showing the method of adjusting Ac:Am.

[0053] Figure 7 Test method to indicate leukocyte removal performance.

[0054] Fig. 8A A cross section in the thickness direction of the filtration layer of Example A1 (a cross section obtained by cutting in the thickness direction) is shown.

[0055] Figure 8B for Fig. 8A Enlarged view of the cross section.

[0056] Fig. 9The in-plane porosity in the thickness direction of the filtration layer of Example A1 is shown.

[0057] Fig.10 The in-plane porosity in the thickness direction of the filtration layer of Example A12 is shown.

[0058] Fig.11 The in-plane porosity in the thickness direction of the filtration layer of Comparative Example A1 is shown.

[0059] Fig.12 The in-plane porosity in the thickness direction of the filtration layer of Comparative Example A2 is shown.

[0060] Fig.13 An example of a method for producing a nonwoven fabric is shown. DETAILED DESCRIPTION

[0061] Hereinafter, a mode for implementing the present invention (hereinafter referred to as the present embodiment) will be described in detail. It should be noted that the present invention is not limited to the following embodiment, and can be implemented with various modifications within the scope of the gist thereof.

[0062] Hereinafter, unless otherwise specified, the term "blood" includes blood and liquids containing blood components. Examples of liquids containing blood components include blood products. Examples of blood products include whole blood products, red blood cell products, platelet products, and plasma products.

[0063] <1st blood processing filter>

[0064] One embodiment of the present invention relates to a blood processing filter, comprising:

[0065] a container having an inlet and an outlet for blood, and

[0066] The filter material disposed between the inlet and the outlet in the container,

[0067] The filter material comprises a filter layer (hereinafter also referred to as "the first filter layer").

[0068] The aforementioned filter layer comprises nonwoven fabric,

[0069] 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.

[0070] 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.

[0071] By adjusting the direction of the fibers of the nonwoven fabric contained in the filtration layer, an excellent leukocyte removal rate and an excellent filtration time (filtration speed) can be exhibited.

[0072] Figure 1 A schematic diagram of an embodiment of a blood processing filter (leukocyte removal filter) is shown. Figure 2 for Figure 1 Sectional view along line II-II.

[0073] like Figure 1 and Figure 2 As shown, the blood processing filter 10 has a flat container 1 and a substantially dry filter material 5 contained therein. The container 1 containing the filter material 5 includes two elements: an inlet side container material having an inlet 3 and an outlet side container material having an outlet 4. The space in the flat container 1 is partitioned into a space 7 on the inlet side and a space 8 on the outlet side by the filter material 5.

[0074] In the blood processing filter 1, the inlet-side container material and the outlet-side container material are arranged to sandwich the filter material 5, and the two container materials are structured so that the outer edge 9 of the filter material 5 is sandwiched and held by the holding portions provided in their respective parts.

[0075] In one embodiment, the filter material and the container may be joined by welding or the like, thereby holding the filter material in the container.

[0076] [container]

[0077] Examples of the material of the container include hard resins and flexible resins.

[0078] Examples of the hard resin include phenolic resins, acrylic resins, epoxy resins, formaldehyde resins, urea resins, silicone resins, ABS resins, nylon, polyurethane, polycarbonate, vinyl chloride, polyethylene, polypropylene, polyester, and styrene-butadiene copolymers.

[0079] The flexible resin preferably has thermal and electrical properties similar to those of the filter layer. Examples of the flexible resin include soft polyvinyl chloride, polyurethane, ethylene-vinyl acetate copolymer, polyolefins such as polyethylene and polypropylene, hydrides of styrene-butadiene-styrene copolymer, styrene-isoprene-styrene copolymer or its hydride, and thermoplastic elastomers such as thermoplastic elastomers and polyolefins, and mixtures of softeners such as ethylene-ethyl acrylate. The flexible resin is preferably soft polyvinyl chloride, polyurethane, ethylene-vinyl acetate copolymer, polyolefin, and thermoplastic elastomers containing them as main components, and soft polyvinyl chloride and polyolefin are more preferred.

[0080] Regarding the shape of the container, for example, when the filter material is in the form of a flat plate, it can be formed into a polygonal shape such as a square or hexagon, or a flat shape such as a circle or an ellipse (for example Figure 1 and Figure 2 ). In addition, when the filter medium is cylindrical, the container is also preferably cylindrical.

[0081] [Filter material]

[0082] (1st filter layer)

[0083] The filter medium includes one or more first filter layers. When the filter medium includes a plurality of first filter layers, the plurality of first filter layers may be the same or different.

[0084] The first filter layer preferably includes a nonwoven fabric. The nonwoven fabric is preferably laminated. There is no particular limitation on the material of the nonwoven fabric, and examples thereof include polyester (e.g., polyethylene terephthalate (PET) and polybutylene terephthalate (PBT)), polyamide, polyacrylonitrile, polymethyl methacrylate, polyethylene, polypropylene, etc. By using such a material, denaturation of blood can be prevented. From the viewpoint of affinity with blood preparations and wettability with blood, the material of the nonwoven fabric is preferably polyester, more preferably PET and PBT. The nonwoven fabric may be formed of only one material or of a plurality of materials.

[0085] The nonwoven fabric contained in the first filter layer may have a coating layer on its surface. It should be noted that in this specification, a nonwoven fabric without a coating layer is also referred to as a "fiber substrate". By appropriately selecting the material of the coating layer, the zeta potential of the surface can be easily made to be above 0 mV.

[0086] The coating layer preferably comprises a copolymer, for example, the copolymer comprising a monomer unit having a nonionic hydrophilic group and a monomer unit having a basic nitrogen-containing functional group. By using a copolymer having a basic nitrogen-containing functional group, a positive charge can be imparted to the surface of the nonwoven fabric by coating treatment, and the affinity with leukocytes can be improved.

[0087] 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-vinyl pyrrolidone, and the like. From the viewpoints of ease of availability, ease of handling during polymerization, and performance during blood circulation, the monomer unit having a nonionic hydrophilic group is preferably a monomer unit derived from 2-hydroxyethyl (meth)acrylate. The monomer unit derived from vinyl alcohol is generally produced by hydrolysis after polymerization of vinyl acetate.

[0088] Examples of monomer units having a basic nitrogen-containing functional group include monomer units derived from (meth)acrylic acid derivatives such as diethylaminoethyl (meth)acrylate, dimethylaminoethyl (meth)acrylate, dimethylaminopropyl (meth)acrylate, and 3-dimethylamino-2-hydroxypropyl (meth)acrylate; styrene derivatives such as p-dimethylaminomethylstyrene and p-diethylaminoethylstyrene; vinyl derivatives of nitrogen-containing aromatic compounds such as 2-vinylpyridine, 4-vinylpyridine, and 4-vinylimidazole; and derivatives of the above vinyl compounds formed into quaternary ammonium salts with alkyl halides, etc. From the viewpoints of ease of availability, ease of handling during polymerization, and performance when circulating in blood, monomer units having a basic nitrogen-containing functional group are preferably monomer units derived from diethylaminoethyl (meth)acrylate and dimethylaminoethyl (meth)acrylate.

[0089] When the total mass of the fiber substrate and the coating layer is 1 g, the mass of the coating layer is preferably about 0.1 to 40.0 mg. By setting the coating amount in this range, uniform coating becomes easy, and problems such as clogging of blood cells or deterioration of filtration performance due to biased blood flow can be avoided.

[0090] The mass of the coating layer can be calculated, for example, by the following steps. After the nonwoven fabric (fiber substrate) before the coating layer is loaded is dried in a dryer set at 60°C for 1 hour, the mass (Ag) is measured after the nonwoven fabric is placed in the dryer for more than 1 hour. After the nonwoven fabric loaded with the coating layer is similarly dried in a dryer at 60°C for 1 hour, the mass (Bg) is measured after the nonwoven fabric is placed in the dryer for more than 1 hour. The mass of the coating layer is calculated by the following calculation formula.

[0091] Mass of coating layer relative to the total of nonwoven fabric (fiber substrate) and coating layer (1 g) (mg / g) = (BA) × 1000 / B

[0092] There is no particular limitation on the method for forming a coating layer on a fiber substrate, and examples thereof include a method of immersing the fiber substrate in a coating liquid containing a monomer and / or polymer (copolymer), a solvent as required, and then appropriately removing the coating liquid (immersion method); a method of coating the fiber substrate by bringing a roller immersed in the coating liquid into contact with the fiber substrate (transfer method), etc.

[0093] The nonwoven fabric included in the first filter layer preferably has a basic nitrogen-containing functional group on its peripheral surface.

[0094] The peripheral surface portion of the nonwoven fabric refers to the entire portion of the nonwoven fabric exposed to the outside world. That is, when the nonwoven fabric has a coating layer, the peripheral surface portion is the surface portion of the coating layer. When the nonwoven fabric does not have a coating layer, the peripheral surface portion refers to the surface portion of the fiber substrate.

[0095] The peripheral surface portion of the nonwoven fabric may further have a nonionic hydrophilic group.

[0096] If the basic nitrogen-containing functional group exists on the peripheral surface of the nonwoven fabric, the affinity between the nonwoven fabric and the leukocytes in the blood increases, and the leukocyte removal performance can be improved.

[0097] In addition, if nonionic hydrophilic groups exist on the peripheral surface of the nonwoven fabric, the wettability of the nonwoven fabric surface to blood increases, and the effective filtration area of ​​the nonwoven fabric (the area actually used for filtration) is improved. As a result, two effects are achieved: reduced filtration time and improved removal performance of white blood cells, etc.

[0098] As a method for allowing nonionic hydrophilic groups and basic nitrogen-containing functional groups to exist on the peripheral surface portion of the nonwoven fabric, for example, in the case of a nonwoven fabric having a coating layer, there can be listed a method of coating the nonwoven fabric with a coating material containing a monomer and / or polymer having a nonionic hydrophilic group and a basic nitrogen-containing functional group; in the case of a nonwoven fabric not having a coating layer, there can be listed a method of spinning a fiber material containing a monomer and / or polymer having a nonionic hydrophilic group and a basic nitrogen-containing functional group, etc.

[0099] The ratio of the amount of the basic nitrogen-containing functional group in the peripheral surface portion of the nonwoven fabric to the total amount of the nonionic hydrophilic group and the basic nitrogen-containing functional group is preferably 0.2 to 50.0 mol%, more preferably 0.25 to 10 mol%, further preferably 1 to 5 mol%, and most preferably 2 to 4 mol%. The content of the basic nitrogen-containing functional group and the nonionic hydrophilic group can be measured by analysis using NMR, IR, TOF-SIMS, etc. By thus defining the ratio of the basic nitrogen-containing functional group to the nonionic hydrophilic group, it is possible to ensure stable wettability to blood, suppress unnecessary clogging caused by blood components such as platelets, and effectively remove white blood cells and the like.

[0100] Examples of the nonionic hydrophilic group include an alkyl group, an alkoxy group, a carbonyl group, an aldehyde group, a phenyl group, an amide group, and a hydroxyl group.

[0101] Examples of the basic nitrogen-containing functional group include -NH2, -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 6is an amino group represented by an alkyl group having 1 to 3 carbon atoms.

[0102] (Orientation Degree)

[0103] 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, and 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. Hereinafter, the maximum value of the orientation degree X / orientation degree Y is also referred to as the "maximum orientation ratio".

[0104] The “degree of orientation” indicates the degree to which fibers are oriented in a predetermined direction. For example, a high degree of orientation of fibers in the X-axis direction means that the fibers are arranged in parallel to the X-axis direction to a high degree.

[0105] The “X-axis plane direction” refers to an arbitrary direction in the plane direction of the first filter layer.

[0106] The “Y-axis plane direction” refers to a direction perpendicular to the X-axis in the plane direction of the first filter layer.

[0107] The “planar direction” refers to a direction perpendicular to the thickness direction of the first filter layer.

[0108] The “maximum value of the orientation degree X / orientation degree Y (maximum orientation ratio)” refers to the maximum value among the values ​​of the orientation degree X / orientation degree Y in all the planar directions of the first filter layer.

[0109] The orientation degree can be calculated by the orientation index. The orientation index refers to the degree of orientation of the fiber in a specified direction in the same way as the orientation degree, but the greater the orientation degree, the smaller the orientation index. For example, the orientation index of the fiber in the X-axis direction is determined based on the cross-sectional area of ​​the fiber on a plane orthogonal to the X-axis direction. When the fibers are arranged in a manner parallel to the X-axis direction, the area of ​​the fiber on the plane orthogonal to the X-axis direction decreases. In other words, the orientation index in the X-axis direction decreases.

[0110] If the orientation index in the X-axis plane direction is set as orientation index X and the orientation index in the Y-axis plane direction orthogonal to the X-axis plane direction is set as orientation index Y, then orientation degree X / orientation degree Y can be expressed as orientation index Y / orientation index X.

[0111] The orientation index X and orientation index Y of the nonwoven fabric were obtained by X-ray CT and image analysis using the following method. The X-ray CT device and image analysis software used are as follows.

[0112] X-ray CT device: Rigaku Corporation's high-resolution 3D X-ray microscope nano3DX

[0113] Image analysis software: ImageJ

[0114] The nonwoven fabric sample for X-ray CT measurement was cut into 2.5 mm×2.5 mm in the plane, and X-ray CT measurement was performed on the total thickness without cutting in the thickness direction. The measurement conditions were as follows.

[0115] Image resolution: 0.54μm / pix

[0116] Exposure time: 18 seconds / frame

[0117] Number of projections: 1500 / 180 degrees

[0118] X-ray tube voltage: 40kV

[0119] X-ray tube current: 30mA

[0120] X-ray target: Cu

[0121] Measurement location: The center of the unaffected surface of the cut surface at the end of the specimen

[0122] 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 inside of the nonwoven fabric.

[0123] The tomographic X-ray image obtained by X-ray CT measurement was trimmed into a rectangular parallelepiped of X axis×Y axis×Z axis=500 μm×500 μm×total thickness, and this was used as a three-dimensional image 1 .

[0124] The three-dimensional image 1 is subjected to a median filter of an image processing method under the condition of a radius of 2pix, and then the Otsu method of the image processing method is applied to perform region segmentation. The brightness value of the pixels after region segmentation is set such that air is 0 and the fiber of the nonwoven fabric is 255. The image thus obtained is the three-dimensional image 2.

[0125] The pixels of the brightness value 255 of the three-dimensional image 2 are segmented by an image processing method, and the fibers with a number of pixels of 10,000 pix or less among the fibers with a brightness value of 255 connected as one are removed as noise. The brightness value of the pixels is set so that air is 0 and the fibers of the nonwoven fabric are 255, and the image obtained in this way is used as the three-dimensional image 3.

[0126] In the three-dimensional image 3, for all pixels on the XY plane, one pixel is scanned at a time in the Z direction perpendicular to the XY plane, and the total number of points where the brightness value changes from 0 to 255 and the total number of points where the brightness value changes from 255 to 0 are obtained by image analysis, which is used as the projection area A.XY Similarly, the total number of scans in the X direction on the YZ plane is taken as the projection area A YZ , the total number of scans on the ZX surface in the Y direction is taken as the projection area A ZX The orientation index X and orientation index Y are calculated from these projected areas by the following formula.

[0127] Orientation index X = A YZ / (A XY +A YZ +A ZX )

[0128] Orientation index Y = A ZX / (A XY +A YZ +A ZX )

[0129] In short, the orientation index is obtained by calculating the cross-sectional area (projected area) when observing the nonwoven fabric in that direction, and then proportionally allocating it so that the sum of the projected areas in each three-dimensional direction becomes 1. In other words, the orientation index in each direction is a number from 0 to 1, and the stronger the orientation in that direction, the smaller the value of the orientation index. In other words, if the nonwoven fabric is completely isotropic, the orientation index in the X, Y, and Z directions are all 0.33.

[0130] The maximum value of the orientation degree X / orientation degree Y (maximum orientation ratio) is 1.2 or more, preferably 1.3 to 2.0, and more preferably 1.4 to 1.8. When the filter material includes multiple layers of the first filter layer, it is sufficient that the maximum orientation ratio of the nonwoven fabric contained in at least one layer of the first filter layer is 1.2 or more, but it is preferred that the maximum orientation ratio of the nonwoven fabric contained in all the first filter layers is 1.2 or more. By including at least one first filter layer of nonwoven fabric having a maximum orientation ratio of 1.2 or more, for high-viscosity blood containing aggregates, low-viscosity blood, or blood with an intermediate viscosity, the flow path of the blood within the surface of the first filter layer can be intentionally induced according to the properties of the blood, and the first filter layer can be effectively utilized and / or the optimal flow path can be formed. In this way, the fluidity of the blood and the leukocyte removal ability can be improved. If the maximum orientation ratio is 2.0 or less, the inductivity of the blood within the surface of the first filter layer can be suppressed from being too strong, so there is a tendency to improve the fluidity and leukocyte removal performance.

[0131] In the blood processing filter of one embodiment, the first filter layer is preferably arranged such that the ratio (Ac / Am) of the orientation degree (Ac) of the fibers of the nonwoven fabric in the planar direction of the first filter layer orthogonal to the filtering direction to the orientation degree (Am) of the fibers of the nonwoven fabric in the planar direction of the first filter layer parallel to the filtering direction is 1.2 or more. Ac / Am is more preferably 1.3 to 2.0, and further preferably 1.4 to 1.8.

[0132] The “filtration direction” refers to the direction of blood flow in the blood processing filter, and corresponds to the direction from the inlet to the outlet of the container.

[0133] The "direction of the plane of the first filtration layer orthogonal to the filtration direction" refers to, for example, Figure 3 and 4 As shown, when the plane of the first filter layer 11 is viewed from the front, a direction 13 is perpendicular to the filtering direction 12.

[0134] The "planar direction of the first filtration layer parallel to the filtration direction" refers to, for example, Figure 3 and 4 As shown, when the plane of the first filter layer 11 is viewed from the front, a direction 14 is parallel to the filtering direction 12.

[0135] When treating blood from which leukocytes are difficult to remove due to its low viscosity and high flow rate, if Ac / Am is 1.2 or more, the blood infiltrates the first filter layer slowly, and the residence time of the blood in the first filter layer is prolonged, thereby improving the leukocyte removal capability.

[0136] In the blood processing filter of one embodiment, the first filter layer is preferably arranged such that the ratio (Am / Ac) of the orientation degree (Am) of the fibers of the nonwoven fabric in the planar direction of the first filter layer parallel to the filtering direction to the orientation degree (Ac) of the fibers of the nonwoven fabric in the planar direction of the first filter layer orthogonal to the filtering direction is 1.2 or more. Am / Ac is more preferably 1.3 to 2.0, and further preferably 1.4 to 1.8.

[0137] When treating blood whose flow rate is slow due to high viscosity and whose filtration time is long, if Am / Ac is 1.2 or more, the blood can penetrate the first filter layer faster and the filtration time can be shortened.

[0138] Ac / Am or Am / Ac can be appropriately adjusted by changing the direction of the first filter layer. Figure 5As shown in FIG. 1 , by changing the direction of the nonwoven fabric having a predetermined maximum orientation ratio and cutting the nonwoven fabric at a predetermined rotation angle, a first filtration layer having a predetermined Ac / Am or Am / Ac can be prepared. By arbitrarily changing the direction of the nonwoven fabric having a known maximum orientation ratio, it is possible to easily confirm how the ratio of Ac to Am changes using line vectors.

[0139] In addition, if Figure 6 As shown in FIG. 1 , Am≒Ac can also be formed by changing the direction of cutting a nonwoven fabric having a maximum orientation ratio of 1.2. In this case, at first glance, it is observed that the filter has the same performance as that of a nonwoven fabric having a maximum orientation ratio of 1.0, but in fact, by orienting the fibers obliquely in the filter, it is possible to guide the blood while ensuring a certain residence time in the filter. This can cope with blood with a medium viscosity, a slight amount of aggregates, flow, and a standard leukocyte removal capacity.

[0140] As a further supplement, the in-plane permeation coefficient (Ky) of Patent Document 2 is a concept similar to Ac or Am in this specification, but Ky is a diverse filter material characteristic derived from the fluidity of the liquid in the planar direction and cannot be directly subdivided into numerical values ​​of Ac and Am.

[0141] (Filling rate)

[0142] The first filtration layer preferably has a filling rate of 0.04 to 0.40, more preferably has a filling rate of 0.06 to 0.30, and further preferably has a filling rate of 0.08 to 0.22.

[0143] When the filling rate of the first filter layer is 0.40 or less, the clogging of blood cells is reduced, and there is a tendency to improve the processing speed. In addition, when the filling rate is 0.04 or more, there is a tendency to increase the number of contacts with leukocytes and the like, and the capture rate of leukocytes and the like is improved, and there is also a tendency to improve the mechanical strength of the nonwoven fabric.

[0144] The filling rate of the first filter layer is measured by the following method: the planar area, thickness, mass of the first filter layer cut into any size, and the specific gravity of the nonwoven fabric fiber material constituting the first filter layer are measured and calculated by the following formula (10).

[0145] Filling rate = [mass of the first filter layer (g) ÷ {area of ​​the first filter layer in the plane direction (cm 2 ) × thickness of the first filter layer (cm) ÷ specific gravity of the fiber material of the nonwoven fabric constituting the first filter layer (g / cm 3 ) (10)

[0147] (Texture Index)

[0148] The texture index of the first filter layer corresponding to a thickness of 0.5 mm is preferably 15 or more and 70 or less. If the texture index is 70 or less, the structure of the first filter layer in the thickness direction is uniform relative to the filter surface direction, and blood flows uniformly through the first filter layer, and there is a tendency to improve the removal ability of white blood cells and the like or improve the processing speed. On the contrary, if the texture index is 15 or more, clogging is less likely to occur due to the reduction of the flow resistance, and the processing speed is improved. The texture index is more preferably 15 or more and 65 or less, further 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.

[0149] The texture index refers to the value obtained by multiplying the coefficient of variation (%) of the absorbance of the porous body (nonwoven fabric) detected by each pixel of the CCD camera by 10, by irradiating light from the bottom of the nonwoven fabric and detecting the transmitted light with a charge coupled device camera (hereinafter referred to as a CCD camera).

[0150] The texture index can be measured, for example, using a formation tester FMT-MIII (manufactured by Nomura Corporation in 2002, S / N: 130). The basic settings of the tester have not been changed since the factory was put on the market, and the total number of pixels of the CCD camera can be measured, for example, at about 3400. Specifically, the measurement size can be set to 7 cm × 3 cm (1 pixel size = 0.78 mm × 0.78 mm) for measurement, so that the total number of pixels is about 3400, but the measurement size can be changed according to the shape of the sample so that the total number of pixels is equal to 3400.

[0151] It should be noted that the texture index is greatly affected by the thickness of the nonwoven fabric, and therefore the texture index corresponding to a thickness of 0.5 mm was calculated by the following method.

[0152] First, prepare three nonwoven fabrics with a thickness of less than 0.5 mm, and measure the texture index and thickness of each. For the thickness of the nonwoven fabric, use a constant pressure thickness gauge (e.g., OZAKI, model FFA-12) to measure the thickness of any four points at a measuring pressure of 0.4 N, and take the average value at this time as the thickness of the nonwoven fabric. Next, overlap two of the three nonwoven fabrics measured in a manner such that the thickness is more than 0.5 mm, and measure the texture index and thickness of the two overlapping nonwoven fabrics. After completing the measurement of the texture index of all three combinations, find the regression line formula of the thickness and the texture index, and use this formula to find the texture index equivalent to a thickness of 0.5 mm.

[0153] When the thickness of two nonwoven fabrics does not reach 0.5 mm, the texture index can be measured by overlapping multiple nonwoven fabrics so that the thickness after overlapping is 0.5 mm or more, and then the texture index can be measured by reducing the nonwoven fabrics so that the thickness after overlapping is less than 0.5 mm. For the combination of all nonwoven fabrics with a thickness of less than 0.5 mm after overlapping, the texture index can be measured, and the regression line formula of thickness and texture index can be obtained, and the texture index of 0.5 mm thickness can be obtained by interpolation from the formula.

[0154] On the other hand, when the thickness of a nonwoven fabric is greater than 0.5 mm, three nonwoven fabrics are prepared, and two of the three are overlapped to measure the texture index and thickness. The texture index of all nonwoven fabric combinations can be measured, and a regression line formula of thickness and texture index can be obtained, and the texture index of a thickness of 0.5 mm can be obtained by extrapolation from the formula.

[0155] The three or more nonwoven fabrics used in the measurement of the texture index are preferably cut from the same filter layer. Usually, they are substantially homogeneous nonwoven fabrics, that is, nonwoven fabrics with the same physical properties (material, fiber diameter, bulk density, filling rate, etc.). However, if the required number of substantially homogeneous nonwoven fabrics cannot be obtained from the same filter layer, nonwoven fabrics of the same type of filter layer may be combined for measurement.

[0156] (Specific surface area)

[0157] The specific surface area of ​​the first filtration layer is preferably 0.8 m 2 / g or more and 3.2m 2 / g or less. If the specific surface area is 3.2m 2 / g or less, the adsorption of useful components such as plasma proteins in blood processing to the filter element is suppressed, and there is a tendency to improve the recovery rate of useful components. 2 / g or more, the adsorption amount of leukocytes and the like increases, so there is a tendency for the removal ability of leukocytes and the like to improve.

[0158] The specific surface area of ​​the first filtration layer is more preferably 1.0 m 2 / g or more and 3.2m 2 / g or less, more preferably 1.1m 2 / g or more and 2.9m 2 / g or less, particularly preferably 1.2m 2 / g or more and 2.9m 2 / g or less, most preferably 1.2m 2 / g or more and 2.6m 2 / g or less.

[0159] The specific surface area refers to the surface area of ​​the first filter layer per unit mass and is a value measured by a BET adsorption method using krypton as the adsorption gas. For example, it can be measured using a Tri-Star 3000 device manufactured by Micromeritics.

[0160] The larger the specific surface area of ​​the first filter layer, the larger the area that can adsorb cells, plasma proteins, etc. when the filter layer of the same mass is used to process blood.

[0161] (Breathable resistance)

[0162] The air permeability resistance of the first filter layer is preferably 25 Pa·s·m / g to 100 Pa·s·m / g, more preferably 30 Pa·s·m / g to 90 Pa·s·m / g, and further preferably 40 Pa·s·m / g to 80 Pa·s·m / g.

[0163] When the air resistance is 25 Pa·s·m / g or more, the number of contacts with leukocytes etc. increases, and it tends to be easier to capture leukocytes etc. When the air resistance is 100 Pa·s·m / g or less, the clogging of blood cells decreases, and the processing speed tends to improve.

[0164] The air permeability resistance of the first filter layer is a value measured as a differential pressure generated when a fixed flow rate of air is passed through the first filter layer. The value is as follows: The first filter layer is placed on the air permeability hole of an air permeability tester (e.g., KES-F8-AP1 manufactured by Katotech KK) and the air is measured at a flow rate of 4 mL / cm 2 / second flow rate when the air is allowed to flow for about 10 seconds (Pa·s / m), the pressure loss is divided by the unit area weight of the first filter layer (g / m 2 ) and the value obtained. The cut-out position was changed and the measurement was performed 5 times, and the average value was taken as the air permeability resistance.

[0165] A high air permeability resistance of the first filter layer means that air does not easily pass through, and the fibers constituting the first filter layer are tightly or evenly wound, indicating that the first filter layer has a property that the blood preparation does not easily flow through. Conversely, a low air permeability resistance of the first filter layer means that the fibers constituting the first filter layer are coarse or unevenly wound, indicating that the first filter layer has a property that the blood preparation easily flows through.

[0166] (Average flow pore size)

[0167] The mean flow pore size of the first filter layer is preferably less than 8.0 μm. If the mean flow pore size is less than 8.0 μm, the number of contacts with leukocytes and the like increases, and the capture of leukocytes and the like becomes easier. When the mean flow pore size is greater than 1.0 μm, the clogging of blood cells decreases, and there is a tendency for the processing speed to increase. The mean flow pore size is more preferably greater than 1.5 μm and less than 7.5 μm, further preferably greater than 2.5 μm and less than 7.0 μm, particularly preferably greater than 3.5 μm and less than 6.5 μm, and most preferably greater than 4.5 μm and less than 6.5 μm.

[0168] The mean flow pore size of the first filtration layer can be measured in accordance with ASTM F316-86 using Perm-Porometer CFP-1200AEXS (automatic pore size distribution measurement system for porous materials) manufactured by PMI.

[0169] (Critical Wetting Surface Tension)

[0170] The critical wetting surface tension (CWST) of the first filter layer is preferably 70 dyn / cm or more, more preferably 75 dyn / cm or more. In the first filter layer with such a critical wetting surface tension, stable wettability to blood is ensured, so that platelets in a blood product can pass through while effectively removing white blood cells and the like. There is no particular upper limit to the CWST, and for example, it may be 200 dyn / cm, 150 dyn / cm, 100 dyn / cm, etc.

[0171] CWST refers to the value obtained by the following method. That is, aqueous solutions with different concentrations of sodium hydroxide, calcium chloride, sodium nitrate, acetic acid or ethanol are prepared in a manner that the surface tension changes every 2 to 4 dyn / cm. For the surface tension (dyn / cm) of each aqueous solution, 94 to 115 are obtained in the sodium hydroxide aqueous solution, 90 to 94 in the calcium chloride aqueous solution, 75 to 87 in the sodium nitrate aqueous solution, 72.4 in pure water, 38 to 69 in the acetic acid aqueous solution, and 22 to 35 in the ethanol aqueous solution ("Chemical Handbook Basic Edition II" Revised 2nd Edition, edited by the Chemical Society of Japan, Maruzen, 1975, page 164). The aqueous solutions with different surface tensions of 2 to 4 dyn / cm obtained in this way are placed on the non-woven fabric in order from the aqueous solution with the lowest surface tension, 10 drops each, and left for 10 minutes. After leaving for 10 minutes, the state in which 9 or more of the 10 drops are absorbed by the non-woven fabric is defined as wet, and the state in which less than 9 of the 10 drops are absorbed is defined as non-wet. If the nonwoven fabric is measured sequentially from the liquid with the smallest surface tension, the nonwoven fabric changes from the wet state to the non-wet state. At this time, the average value of the surface tension of the liquid in which the wet state is observed last and the surface tension of the liquid in which the non-wet state is observed first is defined as the CWST value of the nonwoven fabric. For example, when the nonwoven fabric is wetted by a liquid with a surface tension of 64 dyn / cm and is non-wetted by a liquid with a surface tension of 66 dyn / cm, the CWST value of the nonwoven fabric is 65 dyn / cm.

[0172] (Average fiber diameter)

[0173] The average fiber diameter of the nonwoven fabric contained in the first filter layer is preferably 0.3 μm to 3.0 μm, more preferably 0.5 μm to 2.5 μm. By being within this range, clogging can be avoided while improving the leukocyte removal performance.

[0174] The average fiber diameter refers to a value obtained according to the following procedure.

[0175] Specifically, portions considered to be substantially uniform are sampled from several locations of the nonwoven fabric actually constituting the filter layer or one or more nonwoven fabrics substantially homogeneous therewith, and photographs of fibers in the sampled nonwoven fabric are taken using a scanning electron microscope so that their diameters can be revealed.

[0176] Continue to take photos until a total of 100 diameters are taken. For the photos obtained in this way, measure the diameters of all the fibers shown. Here, the diameter refers to the width of the fiber at right angles to the fiber axis. The value obtained by dividing the sum of the diameters of all the measured fibers by the number of fibers is the average fiber diameter. However, the following data are not included: if multiple fibers overlap and their diameters cannot be accurately measured due to the shadows of other fibers, if multiple fibers melt and become coarse fibers, if fibers with significantly different diameters are mixed, if the focus of the photo is deviated and the boundaries of the fibers are unclear, etc.

[0177] In addition, when the filter layer includes multiple nonwoven fabrics, if the fiber diameters measured in each nonwoven fabric are significantly different, they are different types of nonwoven fabrics, so the boundary surface between the two is found and the average fiber diameters of the two are re-measured. Here, "average fiber diameters are significantly different" means that there is a statistically significant difference.

[0178] (Bulk density)

[0179] The bulk density of the first filtration layer is preferably 0.05 to 0.50 g / cm 3 , more preferably 0.07 to 0.40 g / cm 3 , more preferably 0.10 to 0.30 g / cm 3 If the bulk density of the first filter layer is 0.50 g / cm 3 Below, the flow resistance of the first filter layer decreases and the clogging of blood cells decreases, and there is a tendency for the processing speed to improve. In addition, if the bulk density is 0.05 g / cm 3 If the above-mentioned amount is exceeded, the number of contacts with leukocytes and the like tends to increase, thereby facilitating the capture of leukocytes and the like, and there is a possibility that the mechanical strength of the first filter layer increases.

[0180] The “bulk density of the first filtration layer” was determined as follows: a nonwoven fabric was cut out of a portion considered to be uniform in size of 2.5 cm×2.5 cm, and the weight per unit area (g / m 2 ) and thickness (cm), and the weight per unit area was divided by the thickness to obtain the bulk density. The weight per unit area and the thickness were measured three times with different cutout locations, and the average value was taken as the bulk density.

[0181] The weight per unit area of ​​the first filter layer is calculated as follows: a sample of nonwoven fabric is taken from a portion that is considered to be uniform and has a size of 2.5 cm × 2.5 cm, the weight of the nonwoven fabric sheet is measured, and the weight is converted into a mass per square meter. In addition, the thickness of the first filter layer is calculated as follows: a sample of nonwoven fabric is taken from a portion that is considered to be uniform and has a size of 2.5 cm × 2.5 cm, and the thickness of the center (one point) is measured using a constant pressure thickness gauge. The pressure of the constant pressure thickness gauge load is set to 0.4 N, and the area of ​​the measurement portion is set to 2 cm 2 .

[0182] (Non-crystallization heat and crystallization melting heat)

[0183] Blood processing filters are usually sterilized by steam heating before use. It is believed that the physical structure of the nonwoven fabric included in the filter layer undergoes significant changes due to the steam heating. If the nonwoven fabric shrinks in the plane direction, for example Figure 1 and Figure 2 In a blood processing filter having such a structure, the structure of the holding portion becomes unstable, and there is a possibility that the removal capability of the blood processing filter for white blood cells and the like and the handling properties thereof will be reduced.

[0184] From this viewpoint, the heat of non-crystallization of the nonwoven fabric contained in the filter layer before steam heating treatment is preferably 5 J / g or less, more preferably 3 J / g or less, further preferably 2 J / g or less, and particularly preferably 1 J / g or less. "Heat of non-crystallization" is an index indicating the crystallinity of the resin, and the smaller the value, the higher the crystallinity of the resin.

[0185] By using a filter layer using a nonwoven fabric that satisfies the above-mentioned non-crystallization heat, the filtering performance and handling properties of the blood processing filter are improved.

[0186] For example, Figure 1 and Figure 2 In the blood treatment filter formed by clamping and holding the filter material including the filter layer with a hard container, even after steam heating treatment, the repulsion strength of the filter material to the container holding portion is increased, and the clamping between the container holding portion and the filter material is maintained in a firm state, so that the side leakage phenomenon can be suppressed and the removal capacity of white blood cells, etc. can be improved. It should be noted that the side leakage phenomenon refers to the phenomenon that blood does not penetrate the filter material but leaks between the holding portion and the filter material, thereby flowing from the inlet space to the outlet space.

[0187] In addition, in the case of a blood treatment filter formed by clamping a filter material with a flexible container and joining the container and the filter material by high-frequency welding, by controlling the non-crystallization heat of the non-woven fabric to be below a fixed value, the strength of the joint between the container and the filter material is improved, and the centrifugal resistance of the blood treatment filter (the difficulty of breaking the joint between the container and the filter material when the blood treatment filter is centrifuged (when a centrifugal force is applied)) is improved. The reason why the strength of the high-frequency welding joint between the container and the filter material is improved if the non-crystallization heat of the non-woven fabric contained in the filter layer is controlled to be below a fixed value is not yet clear, but it is believed that if the crystallinity increases, the repulsive force of the non-woven fabric increases during high-frequency welding, thereby suppressing excessive melting caused by the crimping of the non-woven fabric, and forming a uniform joint (without sinkholes, etc. caused by excessive melting).

[0188] Furthermore, the value obtained by subtracting the non-crystallization heat from the crystallization heat of the non-woven fabric contained in the filter layer before the steam heating treatment is preferably 50 J / g or more, more preferably 55 J / g or more, further preferably 60 J / g or more, and particularly preferably 65 J / g or more. This "value obtained by subtracting the non-crystallization heat from the crystallization heat" is also an indicator of the crystallinity of the resin, and the larger the value, the higher the crystallinity of the resin. By further increasing the crystallinity, the changes in the physical properties of the filter layer before and after the steam heating treatment (shrinkage, etc.) are further suppressed, and the removal ability of white blood cells, etc., as described above, is improved.

[0189] The heat of non-crystallization and the heat of crystallization fusion are values ​​measured by a differential scanning calorimeter method (DSC method) for a nonwoven fabric (fiber substrate). The measurement method is described below.

[0190] 3-4 mg of nonwoven fabric (fiber substrate) was separated and installed in an aluminum standard container, and the initial temperature rise curve (DSC curve) was measured at an initial temperature of 35°C, a temperature rise rate of 10°C / min, and a nitrogen flow of 50 mL / min. The exothermic peak and the melting peak (endothermic peak) were detected from the initial temperature rise curve (DSC curve), and the calorific value (J) obtained from each peak area was divided by the nonwoven fabric mass to calculate the non-crystallization heat (J / g) and the crystal melting heat (J / g).

[0191] As a measuring apparatus, for example, TA-60WS system manufactured by Shimadzu Corporation can be used.

[0192] (X-ray crystallinity)

[0193] In this embodiment, the X-ray crystallinity of the nonwoven fabric included in the filter layer before the steam heating treatment is preferably 60 or more, more preferably 63 or more, and further preferably 66 or more. The crystallinity of the nonwoven fabric is further increased, and the change (shrinkage, etc.) of the physical properties of the filter layer before and after the steam heating treatment is suppressed, thereby improving the ability to remove white blood cells and the like as described above.

[0194] X-ray crystallinity is determined by X-ray diffraction.

[0195] The measurement can be performed using an X-ray diffraction apparatus (for example, MiniFlexII (Rigaku Corporation, model 2005H301)) in the following measurement procedures 1) to 5).

[0196] 1) A piece of nonwoven fabric (fiber base material) with a size of 3 cm×3 cm is mounted on the sample stand.

[0197] 2) The measurement was carried out under the following conditions.

[0198] Scanning range: 5°~50°

[0199] Sampling width (width of collected data): 0.02°

[0200] Scanning speed: 2.0° / min

[0201] Voltage: 30kV

[0202] Current: 15mA

[0203] 3) After the measurement, data showing the peaks of the amorphous part and the crystalline part separated are obtained.

[0204] 4) Based on the data in 3), the amorphous peak area (Aa) and the total peak area (At) are calculated. For example, the data measured in 3) are opened using analytical software (MDI JADE 7) and the "automatic peak separation" function is implemented. As a result, the amorphous peak area (Aa) and the total peak area (At) are automatically calculated.

[0205] 5) The crystallinity was calculated from the amorphous peak area (Aa) and the total peak area (At) by the following formula.

[0206] Crystallinity (%) = (At-Aa) / At×100

[0207] A nonwoven fabric having an uncrystallization heat of less than 5 J / g before steam heating treatment, a nonwoven fabric having a value of 50 J / g or more obtained by subtracting the uncrystallization heat from the crystal melting heat, and a nonwoven fabric having an X-ray crystallinity of 60 or more can be easily manufactured, for example, by selecting their materials and manufacturing conditions as described below.

[0208] (Area shrinkage)

[0209] In this 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. If the area shrinkage is 10% or less, the uniformity of the pore size is maintained even after sterilization, the variation of the processing speed can be prevented, and there is a tendency to achieve a stable performance balance, so it is preferred.

[0210] In this regard, polybutylene terephthalate has a faster crystallization rate than other polyester fibers, such as polyethylene terephthalate fibers, and its crystallinity is easy to increase. Therefore, even if harsh steam heating treatments such as high-temperature and high-pressure sterilization are performed, it is not easy to shrink in the planar direction (the area shrinkage rate is easy to reduce). Therefore, it can exert a stable removal ability and processing speed of white blood cells, etc. without relying on sterilization conditions.

[0211] The area shrinkage rate of nonwoven fabric refers to the value calculated by the following formula after accurately measuring the longitudinal and transverse dimensions of a nonwoven fabric (fiber substrate) cut into a square of approximately 20 cm × 20 cm, heat treating the nonwoven fabric at 115°C for 240 minutes without fixing the nonwoven fabric with needles, and then measuring the longitudinal and transverse dimensions again.

[0212] Area shrinkage (%) = (longitudinal length of nonwoven fabric before heat treatment (cm) × horizontal length of nonwoven fabric before heat treatment (cm) - longitudinal length of nonwoven fabric after heat treatment (cm) × horizontal length of nonwoven fabric after heat treatment (cm)) ÷ (longitudinal length of nonwoven fabric before heat treatment (cm) × horizontal length of nonwoven fabric before heat treatment (cm)) × 100

[0213] In the case of manufacturing a blood processing filter by sandwiching and holding the filter material between two parts, namely, the container material constituting the outlet side and the inlet side of the hard container (for example Figure 1 and Figure 2 In the case shown in the figure, when the filter material includes multiple non-woven fabrics, if a non-woven fabric with high crystallinity is used as the non-woven fabric in contact with the outlet side container material (the non-woven fabric arranged at the position closest to the outlet side container material), the holding portion of the outlet side container material after the steam heating treatment can clamp the filter material more strongly, thereby suppressing the phenomenon that blood does not penetrate the filter material and leaks between the holding portion and the filter material, thereby directly flowing from the inlet space to the outlet space (side leakage phenomenon), and the removal ability of white blood cells, etc. is improved, which can further improve the performance as a blood processing filter.

[0214] That is, when a blood processing filter is produced by clamping and holding the filter material between two parts, namely, container materials on the outlet side and the inlet side of a rigid container, the non-woven fabric contained in the filter material that is in contact with the aforementioned container material on the outlet side preferably has the following (1), and more preferably also has (2) and / or (3) in addition to (1).

[0215] (1) The heat of non-crystallization before steam heating is 5 J / g or less

[0216] (2) The value obtained by subtracting the heat of non-crystallization from the heat of melting of the crystal before steam heating treatment is 50 J / g or more

[0217] (3) The X-ray crystallinity before steam heating treatment is 60 or more

[0218] In addition, when a blood treatment filter is manufactured by clamping and holding the filter material with two parts, namely, container materials on the outlet side and the inlet side of a rigid container, if the crystallinity of all non-woven fabrics contained in the filter material is high, it is excellent from the viewpoint of the ability to remove white blood cells and the like after steam heating treatment. However, since the repulsion strength of the filter material is increased, the ease of clamping, holding or joining the filter material with the container material is poor. Therefore, from the viewpoint of productivity during the manufacture of the blood treatment filter, the crystallinity of the non-woven fabrics contained in the filter material other than the non-woven fabrics in contact with the inlet side container material and the outlet side container material (or, the non-woven fabrics in contact with the inlet side container material and the outlet side container material and a specified number of non-woven fabrics (usually one to several sheets) arranged adjacent to them) is preferably not too high.

[0219] For example, in a case where the filter material held in a rigid container includes a second filter layer (described later) and a first filter layer in sequence from the inlet side, from the viewpoint of productivity during the manufacture of the blood processing filter, it is preferred that, among the multiple nonwoven fabrics included in the first filter layer, the nonwoven fabric in contact with the aforementioned container material on the outlet side (as well as a specified number of nonwoven fabrics arranged adjacent thereto) at least satisfies the above-mentioned (1), and a part or all of the other nonwoven fabrics do not satisfy the above-mentioned (1), or even if they do, have a larger heat of non-crystallization before steam heating treatment than the nonwoven fabric in contact with the container material on the outlet side.

[0220] [2nd filter layer]

[0221] The blood processing filter may include a further filter layer in addition to the first filter layer within a range not impairing the effects of the present invention. For example, the blood processing filter may include one or more second filter layers between the inlet of the container and the first filter layer.

[0222] The second filter layer preferably has a structure suitable for removing micro aggregates contained in blood. The second filter layer preferably includes a nonwoven fabric. As the material of the nonwoven fabric, for example, the same material as the nonwoven fabric contained in the first filter layer can be cited.

[0223] 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, further preferably 30 μm to 40 μm and / or 10 μm to 20 μm from the viewpoint of removing fine aggregates in blood.

[0224] In the method of arranging the second filter layer upstream of the first filter layer, even if aggregates are generated in the blood, the aggregates are captured by the nonwoven fabric of the second filter layer on the upstream side (inlet side) with a coarse mesh, and the amount of aggregates reaching the nonwoven fabric of the first filter layer on the downstream side (outlet side) with a fine mesh is reduced. Therefore, clogging of the first filter layer due to aggregates is suppressed.

[0225] The bulk density of the second filtration layer is preferably 0.05 to 0.50 g / cm 3 , more preferably 0.10 to 0.40 g / cm 3 If the bulk density of the second filter layer is 0.50 g / cm 3 The following is because the clogging of the nonwoven fabric caused by the capture of aggregates, leukocytes, etc. is suppressed, and there is a tendency for the filtration rate to improve. In addition, if the bulk density of the nonwoven fabric is 0.05 g / cm 3 As described above, the ability to capture aggregates increases, clogging of the nonwoven fabric of the first filtration layer is suppressed, the filtration rate tends to be improved, and the mechanical strength of the nonwoven fabric tends to be improved.

[0226] [Third filter layer]

[0227] The filter medium of the blood processing filter may further include one or more third filter layers between the first filter layer and the outlet portion of the container within a range not impairing the effects of the present invention.

[0228] Furthermore, the filter medium of the blood processing filter may further include one or more second filter layers between the inlet of the container and the first filter layer, and one or more third filter layers between the first filter layer and the outlet of the container.

[0229] The structure of the third filter layer may be appropriately adjusted according to the required performance.

[0230] The third filter layer preferably comprises a fibrous porous medium such as a nonwoven fabric, a woven fabric, a mesh, or a known filter medium such as a porous body having three-dimensional mesh-like continuous pores. As raw materials thereof, for example, polypropylene, polyethylene, styrene-isobutylene-styrene copolymer, polyurethane, polyester, etc. can be cited. From the perspective of productivity and the welding strength of the blood treatment filter, it is preferred that the third filter layer comprises a nonwoven fabric. Since the flow of blood becomes more uniform, it is particularly preferred that the third filter layer has a plurality of protrusions by embossing or the like.

[0231] The average fiber diameter of the nonwoven fabric contained in the third filtration layer is preferably 3 μm to 60 μm, more preferably 4 μm to 40 μm, further preferably 30 μm to 40 μm and / or 10 μm to 20 μm.

[0232] It should be noted that in the case of a blood processing filter having a flat and flexible container, if a third filter layer is configured, it is possible to prevent the filter layer from being pressed against the outlet side container due to the positive pressure on the inlet side generated during filtration, and to prevent the outlet side container from being tightly attached to the filter layer and obstructing blood flow due to the negative pressure on the outlet side. In addition, the fusion property between the flexible container and the filter layer is improved, and therefore it is preferred.

[0233] For the purpose of controlling the selective separation of blood cells, surface hydrophilicity, etc., the surface of each nonwoven fabric constituting the filter layer may be modified by a known technique such as coating, chemical treatment, radiation treatment, etc.

[0234] <First method for producing blood processing filter>

[0235] The method for producing the nonwoven fabric (fiber substrate) is not limited, and the nonwoven fabric can be produced by either a wet method or a dry method. From the perspective of stably obtaining a nonwoven fabric having an appropriate maximum orientation ratio, a melt-blowing method is particularly preferred.

[0236] As a method for manufacturing a nonwoven fabric (fiber substrate), an example of a meltblowing method is described. In the meltblowing method, the molten polymer flow melted in the extruder is filtered through an appropriate filter, introduced into the molten polymer introduction part of the meltblowing die head, and then ejected from the orifice-shaped nozzle. At the same time, the heated gas introduced into the heated air introduction part is introduced into the heated air ejection slit formed by the meltblowing die head and the die lip, and ejected therefrom, so that the aforementioned ejected molten polymer is refined to form ultrafine fibers, and the formed ultrafine fibers are stacked to obtain a nonwoven fabric. Furthermore, when the nonwoven fabric is heat-treated using a hot suction drum, a hot plate, hot water, a hot air heater, etc., a nonwoven fabric with a desired degree of crystallinity can be obtained.

[0237] There is no particular limitation on the method for producing a nonwoven fabric having a maximum orientation ratio of 1.2 or more, and examples thereof include a method of spinning the nonwoven fabric by meltblowing and increasing the winding speed of the collection conveyor (or roller) during collection. If the winding speed is increased, the fibers are more strongly oriented in the conveyor winding direction (length direction), and the difference in orientation with respect to the direction orthogonal thereto (width direction) is relatively increased.

[0238] It should be noted that, if the above method is used, a nonwoven fabric with a small weight per unit area (weight per unit area) and a thin thickness is formed, but by increasing the number of stacked sheets of the nonwoven fabric, a filter material with a desired weight or thickness can be produced. Alternatively, if the conveyor is designed in a manner that can circulate and capture the nonwoven fabric, the nonwoven fabric is sprayed on the conveyor for many times, thereby also being able to collect a nonwoven fabric with a specified weight per unit area. For this method, when assembled on the filter material, the nonwoven fabric is easy to handle due to the high weight per unit area, and there is no need to excessively increase the number of stacked sheets, so the production efficiency of the filter material is improved.

[0239] In addition, a method of reducing the amount of polymer ejected from one spinneret per unit time (single hole ejection amount) can also be cited. If the ejection amount is reduced, the fibers constituting the nonwoven fabric become thinner, so the fibers are strongly oriented in the winding direction of the conveyor. However, if the average fiber diameter of the fiber changes, the leukocyte removal rate and filtration time are affected by the change, so it is preferred not to significantly change the ejection amount.

[0240] In addition, it is also effective to use a polymer with a low intrinsic viscosity in a manner that the resin is stretched thinner. For example, among polyesters, the melting point and melt viscosity of polybutylene terephthalate resins are generally low compared to polyethylene terephthalate resins, so by using polybutylene terephthalate resins, it is easy to make non-woven fabrics with a high degree of orientation in the length direction during spinning. It should be noted that for resin selection, the melting point of copolymers (copolymers) and polymers containing impurities such as additives is easily reduced compared to so-called homopolymers (single polymers), so by appropriately selecting these resins, the melt viscosity can also be adjusted to the most appropriate.

[0241] More specifically, by using PBT resin and producing under the following conditions, a nonwoven fabric having a maximum orientation ratio of 1.2 or more can be produced.

[0242] ·Collection conveyor speed: 4.0~6.0(m / sec)

[0243] ·Single hole discharge volume: 0.10~0.21(g / (minute·hole))

[0244] Intrinsic viscosity (IV): 0.63~0.82 (dL / g)

[0245] Die head temperature: 270~290(℃)

[0246] Air pressure: 0.25~0.40(MPa)

[0247] In the above case, it is found that the melt viscosity (shear rate 100 (1 / sec), 280° C.) is 100 to 500 (Pa·s).

[0248] Among them, it is effective to first set the intrinsic viscosity and the single hole ejection amount, as well as the die temperature, and then adjust the conveyor speed while confirming the orientation degree. The reason is that, according to the melt viscosity of the resin that depends on the intrinsic viscosity and the die temperature, a strong pressure is applied to the die during ejection, and the die may break, so a low single hole ejection amount has to be set. In addition, if the die temperature is set to 290°C or less, in the case of PBT, fiber discoloration caused by resin decomposition can be suppressed, so it is preferred.

[0249] However, the single-hole ejection volume is a parameter directly related to the average fiber diameter of the non-woven fabric. Therefore, when the ejection volume is changed, in order to obtain the specified average fiber diameter, the pressure of the heated air must also be adjusted at the same time. For example, when the ejection volume is reduced, the average fiber diameter can be maintained by reducing the pressure of the heated air. In addition, after setting the single-hole ejection volume, in order to obtain the specified non-woven fabric weight, the capture time on the conveyor must be calculated and set. In other words, the single-hole ejection volume also affects the production volume of the non-woven fabric. Therefore, considering the productivity and quality of the non-woven fabric, it is also necessary to return to the selection of the resin and ejection volume.

[0250] Finally, the distance between the nozzle and the conveyor does not significantly affect the orientation ratio of the nonwoven fabric, but it is important as a means of adjusting the thickness of the nonwoven fabric. It is usually adjusted within 3 to 60 cm. By shortening the distance between the nozzle and the conveyor, the thickness can be reduced. 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 by adjusting the distance between the nozzle and the conveyor to 3 to 10 cm. 3 .

[0251] <Second blood processing filter>

[0252] One embodiment of the present invention relates to a blood processing filter, comprising:

[0253] a container having an inlet and an outlet for blood, and

[0254] The filter material disposed between the inlet and the outlet in the container,

[0255] The filter material comprises one or more filter layers (hereinafter also referred to as "the first filter layer").

[0256] The filter layer has, in a cross section in the thickness direction, a space having a maximum length in the planar direction of 50 μm or more and a maximum length in the thickness direction of 15 μm or more.

[0257] Since the first filter layer has a predetermined space inside, it is possible to exhibit an excellent leukocyte removal rate and an excellent filtration time (filtration speed).

[0258] [container]

[0259] The container is as described in the item "First blood processing filter".

[0260] [Filter material]

[0261] (1st filter layer)

[0262] The filter material includes one or more first filter layers. When the filter material includes multiple first filter layers, 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. Taking into account the deviation in physical properties during spinning, samples may be taken from at least three locations in the spinning width direction (for example, one location from the left end to near the center, one location near the center, and one location from near the center to the right end), thereby determining the average thickness of the first filter layer. The size of the sample is set to 2.5 cm × 2.5 cm, and the center (1 location) is measured using a constant pressure thickness gauge to determine the thickness. The pressure of the constant pressure thickness gauge load is set to 0.4 N, and the area of ​​the measuring portion is set to 2 cm 2 When the spinning width direction cannot be specified, the measurement is performed by sampling the portion used as the filtration portion of the filter.

[0263] The first filter layer preferably includes a nonwoven fabric. The nonwoven fabric is as described in the section of <First blood processing filter>.

[0264] The nonwoven fabric included in the first filter layer may have a coating layer on its surface. The coating layer is as described in the section of <First blood processing filter>.

[0265] The nonwoven fabric included in the first filter layer preferably has a basic nitrogen-containing functional group on its peripheral surface. The nonwoven fabric may further have a nonionic hydrophilic group on its peripheral surface. The basic nitrogen-containing functional group and the nonionic hydrophilic group are as described in the section <First blood processing filter>.

[0266] (Inner Space)

[0267] The first filter layer has a space having 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 cross section obtained by cutting in the thickness direction) (for example, see Fig. 8A and Figure 8B ). By having a space of this size, clogging caused by blood cells, microaggregates, etc. contained in the blood is avoided, and the effective filtration area is increased, thereby improving the leukocyte removal performance and filtration time. When the filter material contains multiple layers of the first filter layer, it is sufficient as long as at least one of the first filter layers has the aforementioned internal space, but it is preferred that all the first filter layers have the aforementioned internal space.

[0268] The maximum length of the space in the planar direction is preferably 50 μm to 2000 μm, more preferably 100 μm to 1500 μm, further preferably 200 μm to 1000 μm.

[0269] The maximum length of the space in the thickness direction is preferably 15 μm to 200 μm, more preferably 15 μm to 150 μm, and further preferably 20 μm to 100 μm.

[0270] By setting the upper limit of the maximum length in the plane direction and the thickness direction as mentioned above, blood deviation can be suppressed and the effective filter area can be further increased. In addition, residual blood inside the first filter layer can be prevented and the blood recovery amount can be avoided to reduce.

[0271] The internal space of the first filter layer can be measured by the following method. It should be noted that the size of the internal space of the first filter layer does not substantially change between the state where the first filter layer is housed in the blood processing filter and the state where the first filter layer is removed from the blood processing filter.

[0272] A portion having average physical properties (air permeability resistance, density, etc.) of the filter layer is sampled from a sheet of the first filter layer. Specifically, taking into account the physical property deviation during spinning, samples are taken from at least three locations in the spinning width direction (e.g., one location from the left end to near the center, one location near the center, and one location from near the center to the right end), and the internal space of the cross section in the thickness direction of the sample is measured. If the spinning width direction cannot be specified, samples are taken from the portion used as the filter portion.

[0273] The length of the internal space was determined using the pore size analysis software (PHENOMPOROMETRIC) of the SEM (ProX) manufactured by Phenom World. The pore detection conditions are the initial setting conditions of the software described below. However, if the detection is insufficient due to overlapping pores, the pore detection conditions (Min Contrast, Merge Shared Borders, Conductance, Min Detection, etc.) can be appropriately adjusted.

[0274] The specific measurement method of the internal space is as follows.

[0275] (1) The sample of the first filter layer photographed had a size of about 10 mm x about 3 mm, and a 10 mm side was used for cross-sectional observation. Three samples of a size of about 10 mm x about 3 mm were used for measurement.

[0276] At this time, the first filter layer is cut in a manner that the cross section of the sample is not crushed. It is necessary to observe while maintaining the three-dimensional structure of the first filter layer, so after the first filter layer is immersed in a solution that wets the first filter layer (for example, water, 20% ethanol water. In the case of low hydrophilicity, ethanol water is preferably used), it is immersed in liquid nitrogen to break the fully frozen first filter layer.

[0277] When there is no breakage (for example, when the fibers are bent without being cut, or when the first filter layer is so small that it is not broken, etc.), a method is adopted in which a fixing resin (epoxy resin, etc.) different from that of the fibers constituting the first filter layer is poured between the fibers and cured, and then the cross section is polished and observed.

[0278] (2) The imaging magnification is set to a magnification that allows observation of the entire thickness of the first filter layer (preferably 100 times). The magnification can be optimized according to the thickness of the first filter layer and the size of the internal space.

[0279] (3) For each sample, three cross-sectional images were taken. For the images obtained by the cross-sectional images, the pore size in the plane direction and the pore size in the thickness direction were calculated using aperture analysis software (PHENOM POROMETRIC). The average value of the maximum spatial length of the nine points in each cross-sectional image was taken as the maximum spatial length.

[0280] The initial setting values ​​of the pore size analysis software (PHENOM POROMETRIC) are as follows.

[0281] Min shared borders: 0.3

[0282] Exclude edge particles: Not selected

[0283] Conductance: 0.3

[0284] Min detection size: 2.5

[0285] Foreground kernel size: 15

[0286] Segmenter anisotropic diffuse conductance: 10

[0287] Segmenter anisotropic diffuse iterations: 5

[0288] Segmenter gradient function type: normal

[0289] Segmenter WS lower threshold:0.001

[0290] Merging min size ratio: 2

[0291] Merging kernel size: 3

[0292] (Porosity)

[0293] The first filter layer preferably has a porosity in the plane that varies in the thickness direction. The porosity in the plane refers to the ratio of pores existing in the plane corresponding to a specified position in the thickness direction. A large porosity in the plane means that the fiber density in the plane is small. Specifically, when the porosity in the plane is 1, it means that there are no fibers in the plane. The variation of the porosity in the plane means, for example, that the ratio of pores existing in the plane corresponding to the first position in the thickness direction is different from the ratio of pores existing in the plane corresponding to the second position in the thickness direction.

[0294] For example, Fig. 9 The in-plane porosity in the thickness direction of the nonwoven fabric of Example A1 is shown. Fig. 9 The “position” in the expression “Position” indicates a predetermined position in the thickness direction (distance from the surface of the first filtration layer), and the “porosity” indicates the porosity existing in a plane corresponding to the predetermined position in the thickness direction. Fig. 9 Indicates that the porosity in the plane varies in the thickness direction. On the other hand, Fig.11 The plane porosity in the thickness direction of the nonwoven fabric of Comparative Example A1 shows that the variation of the plane porosity is small. By varying the plane porosity in the thickness direction, clogging can be avoided in addition to the aforementioned internal space contained in the first filter layer and as a whole in the first filter layer.

[0295] In the thickness direction, except for the portion from both ends to 80 μm, the minimum in-plane porosity is called "minimum in-plane porosity" and the maximum in-plane porosity is called "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 being within this range, clogging can be avoided while achieving excellent leukocyte removal performance. It should be noted that the reason for excluding the portion from both ends to 80 μm in the thickness direction is that this portion is affected by the fuzzing of the fibers near the surface of the first filter layer, and the porosity cannot be stably measured.

[0296] The minimum porosity in the plane and the maximum porosity in the plane can be appropriately changed according to the blood to be treated. For example, when treating blood with high viscosity, in order to avoid clogging, the porosity can be increased. On the other hand, when treating blood with low viscosity and a large number of leukocytes, in order to improve the leukocyte removal performance, the porosity can be reduced. Although not particularly limited, the minimum porosity in the plane is preferably 0.72 to 0.85, more preferably 0.75 to 0.83. The maximum porosity in the plane is preferably 0.85 to 1.00, more preferably 0.87 to 0.95.

[0297] The in-plane porosity in the thickness direction of the first filtration layer can be measured by the following method.

[0298] From a first filter layer, taking into account the deviation of physical properties during spinning, samples are taken at least at three locations in the spinning width direction (e.g., one location from the left end to the vicinity of the center, one location near the center, and one location from the vicinity of 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, three points are sampled from the part used as the filter part. The X-ray CT device and image analysis software used are as follows.

[0299] X-ray CT device: Rigaku Corporation's high-resolution 3D X-ray microscope nano3DX

[0300] Image analysis software: ImageJ

[0301] The sample for X-ray CT measurement was cut into pieces of 2.5 mm x 2.5 mm in the plane, and the entire thickness was directly subjected to X-ray CT measurement. The measured thickness was 0.1 mm or more.

[0302] The measurement conditions are as follows.

[0303] Image resolution: 0.54μm / pix

[0304] Exposure time: 18 seconds / frame

[0305] Number of projections: 1500 / 180 degrees

[0306] X-ray tube voltage: 40kV

[0307] X-ray tube current: 30mA

[0308] X-ray target: Cu

[0309] The thickness direction of the nonwoven fabric is defined as the Z axis, the arbitrary direction perpendicular to the Z axis is defined as the X axis, and the direction perpendicular to the X axis and the Z axis is defined as the Y axis. The XY plane is equivalent to the surface of the nonwoven fabric. The X-ray measurement site in the sample is the center part of the surface that is not affected by the cut surface of the sample end.

[0310] The tomographic X-ray image obtained by X-ray CT measurement was trimmed into a rectangular parallelepiped of X axis×Y axis×Z axis=500 μm×500 μm×total thickness, and this was used as a three-dimensional image 1 .

[0311] The three-dimensional image 1 is subjected to a median filter of an image processing method with a radius of 2pix, and then the Otsu method of the image processing method is applied to perform region segmentation. The brightness value of the pixel is set to 0 for air and 255 for nonwoven fabric fibers. The image thus obtained is the three-dimensional image 2.

[0312] The pixels of the brightness value 255 of the three-dimensional image 2 are segmented by an image processing method, and the fibers with a number of pixels of 10,000 pix or less among the fibers with a brightness value of 255 connected as one are removed as noise. The brightness value of the pixels is set so that air is 0 and the fibers of the nonwoven fabric are 255, and the image obtained in this way is used as the three-dimensional image 3.

[0313] In the three-dimensional image 3 , the two-dimensional porosity of each portion per 1 pix is ​​calculated by the following formula in the Z axis which is the thickness direction.

[0314] Porosity = number of air (brightness value 0) pixels in the XY plane with a thickness of 1 pix / total number of pixels in the XY plane with a thickness of 1 pix

[0315] The porosity is calculated for all pixels in the Z-axis direction (the entire thickness direction).

[0316] For at least one of the three samples, it is preferred that the minimum porosity within the plane, the maximum porosity within the plane, and the difference between them are within the above numerical range.

[0317] (Filling rate)

[0318] The first filter layer preferably has a filling rate of 0.09 to 0.26, and more preferably has a filling rate of 0.12 to 0.19. When the filling rate of the first filter layer is 0.26 or less, the clogging of blood cells and microaggregates is reduced, and there is a tendency to improve the processing speed. In addition, when the filling rate of the first filter layer is 0.09 or more, there is a tendency that the number of contacts with leukocytes and the like increases and the capture rate of leukocytes and the like is improved, and there is also a tendency that the mechanical strength of the filter material is improved.

[0319] The filling rate of the first filter layer is measured by the following method. The area, thickness, mass of the planar direction of the cut first filter layer, and the specific gravity of the fiber material of the nonwoven fabric constituting the first filter layer are measured and calculated by the following formula (10). The weight per unit area is calculated as follows: a sample of nonwoven fabric is taken from a portion that is considered to be uniform and has a size of 2.5 cm × 2.5 cm, the weight of the nonwoven fabric sheet is measured, and the weight is converted into a mass per square meter. In addition, the thickness of the first filter layer is calculated as follows: a sample of nonwoven fabric is taken from a portion that is considered to be uniform and has a size of 2.5 cm × 2.5 cm, and the thickness of the center (1 point) is measured using a constant pressure thickness gauge. The pressure of the load using the constant pressure thickness gauge is set to 0.4 N, and the area of ​​the measuring portion is set to 2 cm 2 .

[0320] Filling rate = [mass of the first filter layer (g) ÷ {area of ​​the first filter layer in the plane direction (cm 2 ) × thickness of the first filter layer (cm) ÷ specific gravity of the fiber material of the nonwoven fabric constituting the first filter layer (g / cm 3 ) (10)

[0322] (Texture Index)

[0323] The texture index of the first filter layer is as described in the section of <First blood processing filter>.

[0324] (Specific surface area)

[0325] The specific surface area of ​​the first filtration layer is preferably 0.50 m 2 / g or more and 1.50m 2 / g or less. If the specific surface area is 1.50m 2 / g or less, the adsorption of useful components such as plasma proteins in blood treatment to the filter layer is suppressed, and there is a tendency to improve the recovery rate of useful components. 2 / g or more, the amount of adsorption of leukocytes and the like increases, so there is a tendency for the removal capability of leukocytes and the like to improve. The specific surface area of ​​the first filtration layer is more preferably 0.70 m 2 / g or above and 1.45m 2 / g or less, more preferably 1.10m 2 / g or more and 1.40m 2 / g or less.

[0326] The specific surface area was measured as described in the section of <First blood processing filter>.

[0327] (Breathable resistance)

[0328] The air permeation resistance of the first filter layer is as described in the section of <First blood processing filter>.

[0329] (Average flow pore size)

[0330] The first filter layer preferably has a mean flow pore size of less than 8.0 μm. If the mean flow pore size is less than 8.0 μm, the number of contacts with leukocytes and the like increases, and the capture of leukocytes and the like tends to become easier. When the mean flow pore size is greater than 1.0 μm, the clogging of blood cells decreases, and there is a tendency for the processing speed to increase. The mean flow pore size is more preferably greater than 1.5 μm and less than 7.5 μm, further preferably greater than 2.5 μm and less than 7.0 μm, and most preferably greater than 3.5 μm and less than 6.0 μm.

[0331] The mean flow rate pore size was measured as described in the section of <First blood processing filter>.

[0332] (Critical Wetting Surface Tension)

[0333] The critical wetting surface tension (CWST) of the first filter layer is preferably 70 dyn / cm or more, more preferably 85 dyn / cm or more, and further preferably 95 dyn / cm or more. In the first filter layer with such a critical wetting surface tension, stable wettability to blood is ensured, so that platelets in a blood product can pass through while effectively removing white blood cells and the like. There is no particular upper limit to the CWST, and for example, it may be 200 dyn / cm, 150 dyn / cm, 100 dyn / cm, etc.

[0334] The measurement of CWST is as described in the section of <First blood processing filter>.

[0335] (Average fiber diameter)

[0336] The average fiber diameter of the nonwoven fabric included in the first filter layer is as described in the section of <First blood processing filter>.

[0337] [2nd filter layer]

[0338] The filter material of the blood processing filter may include a further filter layer in addition to the first filter layer within the range not impairing the effect of the present invention. For example, the filter material may include one or more second filter layers between the inlet of the container and the first filter layer.

[0339] The second filter layer is as described in the item <First blood processing filter>. It should be noted that the filling rate of the second filter layer is preferably 0.04 to 0.36, and more preferably 0.07 to 0.29. If 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 can be suppressed, and there is a tendency to improve the filtration rate. On the contrary, if it is 0.04 or more, the ability to capture aggregates increases, the clogging of the first filter layer is suppressed, there is a tendency to improve the filtration rate, and there is a tendency to improve the mechanical strength of the nonwoven fabric.

[0340] [Third filter layer]

[0341] 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, within the range that does not impair the effect of the present invention. In addition, the filter material of the blood processing filter may further include one or more second filter layers between the inlet of the container and the first filter layer, and one or more third filter layers between the first filter layer and the outlet of the container.

[0342] The third filter layer is as described in the section of <First blood processing filter>.

[0343] <Method for manufacturing the second blood processing filter>

[0344] The method for producing the nonwoven fabric (fiber substrate) is not limited, and the nonwoven fabric can be produced by either a wet method or a dry method. When forming a desired space inside the first filtration layer, a melt-blowing method is preferably used.

[0345] As a method for manufacturing a nonwoven fabric (fiber substrate), an example of a meltblowing method is described. In the meltblowing method, the molten polymer flow melted in the extruder is filtered through an appropriate filter, introduced into the molten polymer introduction part of the meltblowing die head, and then ejected from the orifice-shaped nozzle. At the same time, the heated gas introduced into the heated air introduction part is introduced into the heated gas ejection slit formed by the meltblowing die head and the die lip, and ejected therefrom, so that the aforementioned ejected molten polymer is refined to form ultrafine fibers, and the formed ultrafine fibers are stacked on a collection conveyor and a collection drum to obtain a nonwoven fabric. Furthermore, when the nonwoven fabric is heat-treated using a hot suction drum, a hot plate, hot water, a hot air heater, high-pressure steam sterilization, etc., a nonwoven fabric with a small shrinkage rate and a stable shape can be obtained.

[0346] When a rotating conveyor is used for capture, the stacked nonwoven fabric can be spun by stacking the fibers ejected from the rotating conveyor. When a winding belt conveyor is used for capture, the stacked nonwoven fabric can be spun even if it is not a rotating type by setting multiple rows of spinnerets in the length direction. Here, appropriate cooling is performed until the fibers ejected from the spinneret and the newly ejected fibers overlapping the fibers are stacked, thereby forming a specified space inside the filter layer. As a cooling method, for example, a method of extending the time until the fiber layer is stacked on the fiber layer and performing natural cooling can be cited. On the other hand, if the conveyor has a suction function, the fibers are stably captured while the fibers are ventilated, thereby also obtaining a cooling effect. It should be noted that if the cooling is excessive, the fiber welding will not occur at all, and the fiber layer will peel off, and a nonwoven fabric cannot be formed, and the handling property will deteriorate or a reduction in blood recovery rate will be found.

[0347] The internal space of the filter layer can be adjusted by appropriately adjusting the rotation speed of the collection conveyor, the length of the meltblowing die head, the spinning width, the distance between the meltblowing die head and the collection drum (DCD), etc.

[0348] Preferred spinning conditions for the nonwoven fabric described in this specification include the following conditions.

[0349] ·Number of spinnerets of meltblown die: 5~30 (hole / cm)

[0350] · Collection conveyor rotation speed: 100~400 (m / min)

[0351] ·Spraying speed: 0.06~0.10m / s

[0352] ·Single hole discharge volume: 0.12~0.20(g / (minute·hole))

[0353] Heating air volume: 100~400(Nm 3 / hr)

[0354] DCD: 50~1000(mm)

[0355] Among them, the particularly important conditions are the conveyor rotation speed and the ejection movement speed.

[0356] The method of stacking nonwoven fabrics while rotating the collection conveyor in the longitudinal direction of the nonwoven fabrics is effective because it reduces the amount of nonwoven fabrics coated per unit time and per unit area and relatively increases the internal space of the filter layer. In particular, by increasing the rotation speed, the uniformity of the nonwoven fabrics is improved and the internal space of the filter layer is increased.

[0357] In addition, the method of ejecting fibers in the width direction by setting a time difference in the width direction instead of ejecting fibers simultaneously from the spinneret is effective because it can increase the internal space in the plane direction. As for its principle, when the ejection area is reciprocating, a time interval is set between the previous ejection and the subsequent ejection, thereby cooling the previous fiber layer during this period, making it difficult to fuse with the subsequent fiber layer, and as a result, the internal space in the plane direction can be increased. If the time interval is large, the effect is further increased.

[0358] Furthermore, by reducing the ejection moving speed, the previous fiber layer is cooled, so the internal space in the plane direction can be further increased. Here, the ejection moving speed refers to the moving speed of the ejection spinneret region in the width direction per unit time calculated by the following formula.

[0359] <Formula>

[0360] Spraying moving speed = width of collecting conveyor (m) / (switching time (s) × number of spinnerets in width direction)

[0361] For example Fig.13 In the example, the width of the collection conveyor is set to 1.6 m, and 8 spinnerets with a width of 20 cm are set. Fig.13 When spinning is performed continuously while switching from the right end spinneret 1 to the left end spinneret 8 every 2.5 seconds, the ejection moving speed is 1.6 / (2.5×8)=0.08 m / s. This ejection moving speed indicates the substantial speed at which the ejection area expands in the width direction.

[0362] It should be noted that, compared with the time-difference ejection in the width direction, if you want to obtain the same effect more simply, the meltblowing die head itself can be reciprocated in the width direction relative to the conveyor, or the conveyor can be reciprocated in the width direction relative to the die head, thereby obtaining the same effect.

[0363] The number of die spinnerets per unit length is an effective parameter from the viewpoint of improving the uniformity of the plane direction of the nonwoven fabric and controlling the size of the internal space within an appropriate range. In addition, the single-hole ejection amount and DCD are effective for adjusting the coating amount of the nonwoven fabric per unit time and the thickness of the nonwoven fabric, respectively, and relatively controlling the internal space. In particular, if the single-hole ejection amount is reduced, the cooling of the fiber layer is promoted, and the internal space can be relatively increased. However, if it is too small, the resin is too fine, and there is a phenomenon of flying without being captured by the conveyor, so it is preferably adjusted to a fixed range.

[0364] In order to adjust the average fiber diameter of the nonwoven fabric and obtain a fixed leukocyte removal capacity, increasing the heated air volume is effective. However, if it is too high, the resin will be too fine and will not be captured by the conveyor and will fly. Therefore, it is preferred to adjust it to a fixed level according to the single hole discharge volume.

[0365] <Leukocyte removal method>

[0366] The leukocyte removal method includes, for example, a step of removing leukocytes from the leukocyte-containing liquid by passing the leukocyte-containing liquid through a blood processing filter.

[0367] Here, the leukocyte-containing liquid refers to a general term for body fluids containing leukocytes, synthetic blood, and specifically, whole blood, concentrated red blood cell solutions, washed red blood cell suspensions, thawed red blood cell concentrated solutions, synthetic blood, platelet-poor plasma (PPP), platelet-rich plasma (PRP), plasma, frozen plasma, platelet concentrated solutions and buffer-coated (BC), etc., whole blood and liquids composed of a single or multiple blood components prepared from whole blood, or solutions obtained by adding anticoagulants, preservative solutions, etc. to these liquids, or whole blood preparations, red blood cell preparations, platelet preparations, plasma preparations, etc.

[0368] In addition, the liquid obtained by treating the above liquid by the method of this embodiment is referred to as a leukocyte-removed liquid.

[0369] Hereinafter, one embodiment of a method for preparing each blood product by removing leukocytes by a leukocyte removal method will be described.

[0370] (Preparation of Leukocyte-Removed Whole Blood Preparation)

[0371] A whole blood preparation is prepared by adding citrate phosphate dextrose (CPD), citrate phosphate dextrose adenine-1 (CPDA-1), citrate phosphate-2-dextrose (CP2D), acid citrate dextrose formula-A (Acid Citrate Dextrose Formula-A) (ACD-A), acid citrate dextrose formula-B (Acid Citrate Dextrose Formula-B) (ACD-B), a preservation solution such as heparin, an anticoagulant, etc. to collected whole blood, and then, using the blood processing filter of this embodiment, leukocytes are removed from the whole blood preparation, thereby obtaining a leukocyte-removed whole blood preparation.

[0372] When preparing a leukocyte-removed whole blood preparation, when leukocytes are removed before storage, whole blood stored at room temperature or under refrigeration is preferably subjected to leukocyte removal using a blood treatment filter within 72 hours, more preferably within 24 hours, particularly preferably within 12 hours, and most preferably within 8 hours after blood collection at room temperature or under refrigeration, thereby obtaining a leukocyte-removed whole blood preparation. When leukocytes are removed after storage, whole blood stored at room temperature, under refrigeration or under freezing is preferably subjected to leukocyte removal using a blood treatment filter within 24 hours before use, thereby obtaining a leukocyte-removed whole blood preparation.

[0373] (Preparation of Leukocyte-Removed Red Blood Cell Preparation)

[0374] Preservatives and anticoagulants such as CPD, CPDA-1, CP2D, ACD-A, ACD-B, and heparin are added to the collected whole blood. The separation methods of each blood component include: removing white blood cells from the whole blood and then centrifuging; and removing red blood cells after centrifugation of the whole blood or removing white blood cells from red blood cells and BC.

[0375] When the whole blood is centrifuged after leukocytes are removed, the leukocyte-removed whole blood is centrifuged to obtain a leukocyte-removed red blood cell preparation.

[0376] When whole blood is centrifuged before leukocyte removal, there are two types of centrifugation conditions: weak centrifugation conditions for separation into erythrocytes and PRP; and strong centrifugation conditions for separation into erythrocytes, BC, and PPP. After adding a preservation solution such as SAGM, AS-1, AS-3, AS-5, MAP, etc. to erythrocytes separated from whole blood or erythrocytes containing BC as needed, leukocytes are removed from erythrocytes using a leukocyte removal filter, thereby obtaining a leukocyte-removed erythrocyte preparation.

[0377] In the preparation of the leukocyte-removed erythrocyte preparation, whole blood stored at room temperature or under refrigeration can be preferably centrifuged within 72 hours after blood collection, more preferably within 48 hours, particularly preferably within 24 hours, and most preferably within 12 hours.

[0378] In the case of leukocyte removal before storage, leukocytes are preferably removed using a blood treatment filter at room temperature or under refrigeration within 120 hours, more preferably within 72 hours, particularly preferably within 24 hours, and most preferably within 12 hours after blood collection from an erythrocyte preparation stored at room temperature or under refrigeration, thereby obtaining a leukocyte-removed erythrocyte preparation. In the case of leukocyte removal after storage, leukocytes are preferably removed using a blood treatment filter at room temperature, under refrigeration, or under freezing, within 24 hours before use, thereby obtaining a leukocyte-removed erythrocyte preparation.

[0379] (Preparation of Leukocyte-Removed Platelet Preparation)

[0380] To the collected whole blood, a preservation solution or anticoagulant such as CPD, CPDA-1, CP2D, ACD-A, ACD-B, or heparin is added.

[0381] The separation methods of the blood components include: a case where leukocytes are removed from whole blood and then centrifuged; and a case where leukocytes are removed from PRP or platelets after centrifugation of whole blood.

[0382] When leukocytes are removed from whole blood and then centrifuged, the leukocyte-removed whole blood is centrifuged to obtain a leukocyte-removed platelet preparation.

[0383] When whole blood is centrifuged before leukocyte removal, the centrifugation conditions include: weak centrifugation conditions for separation into red blood cells and PRP; and strong centrifugation conditions for separation into red blood cells, BC, and PPP. Under weak centrifugation conditions, leukocytes can be removed from PRP separated from whole blood by a blood treatment filter, and then a leukocyte-removed platelet preparation can be obtained by centrifugation, or PRP can be centrifuged to obtain platelets and PPP, and then leukocytes can be removed by a blood treatment filter to obtain a leukocyte-removed platelet preparation. Under strong centrifugation conditions, BC separated from whole blood is made into a unit or a pool of several to a dozen units, and a preservation solution, plasma, etc. are added to the obtained substance as needed for centrifugation to obtain platelets, and the obtained platelets are removed from the leukocytes by a blood treatment filter, thereby obtaining a leukocyte-removed platelet preparation.

[0384] In the preparation of leukocyte-removed platelet preparations, whole blood stored at room temperature is preferably centrifuged within 24 hours after blood collection, more preferably within 12 hours, and particularly preferably within 8 hours. In the case of leukocyte removal before storage, the platelet preparation stored at room temperature is preferably removed from the blood within 120 hours, more preferably within 72 hours, particularly preferably within 24 hours, and most preferably within 12 hours after blood collection, at room temperature using a blood treatment filter to remove leukocytes, thereby obtaining a leukocyte-removed platelet preparation. In the case of leukocyte removal after storage, it is preferred to remove leukocytes from a platelet preparation stored at room temperature, refrigerated or frozen, using a blood treatment filter within 24 hours before use, thereby obtaining a leukocyte-removed platelet preparation.

[0385] (Preparation of Leukocyte-Depleted Plasma Preparation)

[0386] To the collected whole blood, a preservation solution or anticoagulant such as CPD, CPDA-1, CP2D, ACD-A, ACD-B, or heparin is added.

[0387] The separation methods of the blood components include: a case where leukocytes are removed from whole blood and then centrifuged; and a case where leukocytes are removed from PPP or PRP after centrifugation of whole blood.

[0388] When whole blood is leukocyte-removed and then centrifuged, the leukocyte-removed whole blood is centrifuged to obtain a leukocyte-removed plasma product.

[0389] When whole blood is centrifuged before leukocyte removal, there are two centrifugation conditions: weak centrifugation conditions for separation into red blood cells and PRP; and strong centrifugation conditions for separation into red blood cells, BC, and PPP. In the case of weak centrifugation conditions, after leukocytes are removed from PRP using a blood treatment filter, a leukocyte-removed plasma preparation is obtained by centrifugation, or after PRP is centrifuged into PPP and platelets, leukocytes are removed using a blood treatment filter, thereby obtaining a leukocyte-removed plasma preparation. In the case of strong centrifugation conditions, leukocytes are removed from PPP using a blood treatment filter, thereby obtaining a leukocyte-removed plasma preparation.

[0390] In the preparation of a leukocyte-removed plasma preparation, whole blood stored at room temperature or under refrigeration can be preferably centrifuged within 72 hours after blood collection, more preferably within 48 hours, particularly preferably within 24 hours, and most preferably within 12 hours. Preferably, leukocytes are removed from a plasma preparation stored at room temperature or under refrigeration using a blood treatment filter within 120 hours after blood collection, more preferably within 72 hours, particularly preferably within 24 hours, and most preferably within 12 hours at room temperature or under refrigeration, thereby obtaining a leukocyte-removed plasma preparation. In the case of leukocyte removal after storage, leukocytes are preferably removed from a plasma preparation stored at room temperature, under refrigeration, or under freezing, using a blood treatment filter within 24 hours before use, thereby obtaining a leukocyte-removed plasma preparation.

[0391] As the form of blood collection until the preparation of the leukocyte-removed blood product, it can be carried out in any of the following forms: blood is collected using a blood collection needle connected to a whole blood container, and a container containing whole blood or blood components after centrifugation is connected to a blood treatment filter to remove leukocytes; or blood is collected using a loop that is aseptically connected to at least a blood collection needle, a blood container, and a blood treatment filter, and leukocytes are removed before or after centrifugation; or a container containing blood components obtained by an automatic blood collection device is connected to a blood treatment filter or a blood treatment filter is connected in advance to remove leukocytes, and the present embodiment is not limited to these forms. In addition, whole blood is centrifuged into each component using an automatic component blood collection device, and after adding a preservation solution as needed, any of red blood cells, red blood cells containing BC, BC, platelets, PRP, and PPP are immediately passed through the blood treatment filter to remove leukocytes, thereby obtaining a leukocyte-removed red blood cell product, a leukocyte-removed platelet product, or a leukocyte-removed plasma product.

[0392] In the present embodiment, leukocyte removal can be performed by allowing the leukocyte-containing blood to flow through the blood treatment filter via a tube from a container containing a leukocyte-containing liquid that is located at a higher position than the blood treatment filter, utilizing the height difference. Alternatively, the leukocyte-containing blood can be pressurized and flowed through the inlet side of the blood treatment filter, and / or depressurized and flowed through the outlet side of the blood treatment filter using a pump or the like.

[0393] Example

[0394] The present invention will be described below based on examples, but the present invention is not limited thereto. The performance of the blood processing filter was measured by the following method.

[0395] (Evaluation of leukocyte removal ability and filtration time)

[0396] As the blood used for the evaluation, whole blood was used as follows: 400 mL of blood immediately after blood collection was mixed with 56 mL of CPD solution as an anticoagulant, and the mixture was allowed to stand for 2 hours. Hereinafter, the blood prepared for the blood evaluation is referred to as pre-filtration blood.

[0397] However, in the blood transfusion market, blood stored at room temperature and blood stored under refrigeration are sometimes used, so this time the evaluation is based on both cases.

[0398] The blood bag filled with pre-filtration blood was connected to the inlet of the blood processing filter after steam heating treatment with a 40 cm tube made of vinyl chloride having an inner diameter of 3 mm and an outer diameter of 4.2 mm. Furthermore, the outlet of the blood processing filter was connected to the recovery blood bag with the same 85 cm tube made of vinyl chloride having an inner diameter of 3 mm and an outer diameter of 4.2 mm. Thereafter, the pre-filtration blood was flowed into the blood processing filter from the upper part of the blood bag filled with pre-filtration blood at a height of 140 cm, and the filtration time was measured until the amount of blood flowing into the recovery blood bag reached 0.2 g / min.

[0399] Furthermore, 3 mL of blood (hereinafter referred to as filtered blood) was recovered from the recovery blood bag. The leukocyte removal ability was evaluated by determining the number of residual leukocytes. The number of residual leukocytes was measured using a flow cytometer (device: FACSCanto manufactured by BECTON DICKINSON Co., Ltd.) to determine the number of leukocytes in the filtered blood and calculated according to the following formula. The determination of the number of leukocytes was performed as follows: 100 μL of each blood was sampled and performed using a Leucocount kit (Becton Dickinson and Company, Japan) equipped with beads.

[0400] Residual white blood cell count = log[white blood cell concentration (cells / μL)(filtered blood)] × blood volume (mL)

[0401] In the above filter shape (14 sheets of non-woven fabric, effective filtration area 45cm 2 ) under the conditions of: if the number of residual white blood cells is less than 1×10 6 If the filtration time is short, more blood can be filtered per unit time in the limited space of the blood center, thereby improving the work efficiency. In addition, if the filtration time is long, quality defects such as unexpected hemolysis may occur, resulting in the abandonment of the preparation.

[0402] If the number of residual white blood cells per bag is less than 1×10 6(less than 6Log / Bag) can prevent serious side effects. It is not necessary to use one filter to meet all the requirements of either room temperature stored blood or refrigerated stored blood, because there is no practical obstacle if an appropriate filter is provided according to the use environment. It is preferably less than 5.8Log / Bag, more preferably less than 5.5Log / Bag, and further preferably less than 5.3Log. Since blood has large individual differences, it can be seen that the number of residual white blood cells (logarithm) shows a normal distribution even for the same filter type, and the standard deviation is approximately about 0.20Log. That is, if it is less than 5.8Log, a deviation of 1σ (65%) can be considered to make safer blood preparations, if it is less than 5.5Log, a deviation of 2σ can be considered, and if it is less than 5.3Log, a deviation of 3σ can be considered. In other words, if it is 5.3Log, a high blood correlation ratio of 99.7% can be considered to make preparations, which can dramatically suppress the risk of side effects of transfusion caused by the number of residual white blood cells.

[0403] [Example 1]

[0404] (Manufacturing of filter layer)

[0405] Polybutylene terephthalate (PBT) was spun by melt-blowing to form a nonwoven fabric (fiber substrate). Here, the intrinsic viscosity of the PBT resin was 0.82 (dL / g), the single hole ejection amount was 0.21 (g / (minute·hole)), the pressure of the heated air during ejection was 0.30 (MPa), and the collection conveyor speed was 4.1 (m / second). The collection conveyor was circulated for 8.0 minutes to form a nonwoven fabric on the conveyor. In addition, the die head temperature during spinning was 280°C, and the distance between the nozzle and the collection conveyor was 6 cm.

[0406] The obtained fiber substrate was coated with a hydrophilic polymer by the following method to obtain a nonwoven fabric having a coating layer (first filter layer). It should be noted that the hydrophilic polymer used does not contain a carboxyl group, and the carboxyl equivalent of the nonwoven fabric after coating is 122 μeq / g, which is the same as the carboxyl equivalent of the fiber substrate.

[0407] A copolymer of 2-hydroxyethyl methacrylate (hereinafter referred to as HEMA) and diethylaminoethyl methacrylate (hereinafter referred to as DEAMA) was synthesized by conventional solution free radical polymerization. The polymerization reaction was carried out at 60°C for 8 hours at a monomer concentration of 1 mol / L in ethanol in the presence of 1 / 200 mol of azoisobutyronitrile (AIBN) as an initiator. The fiber substrate was immersed in the ethanol solution of the generated hydrophilic polymer. The fiber substrate taken out from the polymer solution was pressed to remove the excess polymer solution absorbed, and the polymer solution was dried while feeding dry air to form a coating layer covering the surface of the fiber substrate.

[0408] The ratio of the amount of the basic nitrogen-containing functional groups in the peripheral surface portion (surface portion of the coating layer) of the obtained first filter layer to the total amount of the nonionic groups and the basic nitrogen-containing functional groups was 3.0 mol%, and the mass of the coating layer in 1 g of the first filter layer was 1.5 mg / g (fiber substrate+coating layer).

[0409] Table 1 shows various physical properties of the first filter layer.

[0410] (Manufacturing of blood treatment filters)

[0411] Fourteen sheets of the first filtration layer were cut so that the ratio of Am:Ac was 1.2:1 (the direction with a high degree of orientation was aligned with Am), and filled to an effective filtration area of ​​45 cm 2 A blood processing filter is made by ultrasonic welding a soft container.

[0412] The blood processing filter was subjected to steam heating at 115° C. for 59 minutes and then vacuum dried at 40° C. for 15 hours or more. Table 1 shows the performance of the blood processing filter.

[0413] [Examples 2 to 10]

[0414] A nonwoven fabric (fiber substrate) was prepared in the same manner as in Example 1 except that the intrinsic viscosity of the PBT resin, the single hole discharge rate, the collection conveyor speed, and the collection conveyor cycle time were changed as shown in Table 1.

[0415] The coating was carried out in the same manner as in Example 1 to obtain the first filtration layer. Table 1 shows various physical properties of the first filtration layer.

[0416] As shown in Table 1, the direction with a high degree of orientation was aligned with Am, and a blood processing filter was prepared in the same manner as in Example 1. Table 1 shows the performance of the blood processing filter.

[0417] [Examples 11 to 20]

[0418] Examples 11 to 20 correspond to Examples 1 to 10, respectively. In Examples 11 to 20, the direction of the first filter layer of Examples 1 to 10 was changed so that the direction with a high degree of orientation was aligned with Ac as shown in Table 2, and blood processing filters were prepared in the same manner as in Examples 1 to 10. The performance of the blood processing filter is shown in Table 2.

[0419] [Examples 21 to 30]

[0420] Examples 21 to 30 correspond to Examples 1 to 10, respectively. In Examples 21 to 30, the direction of the first filter layer of Examples 1 to 10 was changed so that Am:Ac was 1:1, and blood processing filters were prepared in the same manner as in Examples 1 to 10. The performance of the blood processing filter is shown in Table 3. It should be noted that in Examples 21 to 30, blood with a higher viscosity and containing a relatively large number of aggregates was used compared to the room temperature stored blood used in Examples 1 to 20.

[0421] [Comparative Example 1]

[0422] The intrinsic viscosity of the PBT resin was changed to 0.85 (dL / g), the single-hole ejection volume was changed to 0.23 (g / (minute·hole)), the pressure of the heated air during ejection was changed to 0.32 (MPa), the collecting conveyor speed was changed to 3.5 (m / second), and the collecting conveyor cycle time was changed to 7.3 minutes. Except for this, a nonwoven fabric (fiber base material) was prepared in the same manner as in Example 1.

[0423] The coating was carried out in the same manner as in Example 1 to obtain a filtration layer. Table 4 shows various physical properties of the filtration layer.

[0424] As shown in Table 4, the direction with a high degree of orientation was made to coincide with Am, and a blood processing filter was prepared in the same manner as in Example 1. Table 4 shows the performance of the blood processing filter.

[0425] [Comparative Example 2]

[0426] A blood processing filter was prepared in the same manner as in Comparative Example 1 except that the direction of the filter layer in Comparative Example 1 was changed so that the direction with a high degree of orientation coincided with Ac as shown in Table 4. Table 4 shows the performance of the blood processing filter.

[0427] [Comparative Example 3]

[0428] The intrinsic viscosity of the PBT resin was changed to 0.88 (dL / g), the single-hole ejection volume was changed to 0.25 (g / (minute·hole)), the pressure of the heated air during ejection was changed to 0.35 (MPa), the collecting conveyor speed was changed to 3.2 (m / second), and the cycle time of the collecting conveyor was changed to 6.7 minutes. Except for this, a nonwoven fabric (fiber base material) was prepared in the same manner as in Example 1.

[0429] The coating was carried out in the same manner as in Example 1 to obtain a filtration layer. Various physical properties of the filtration layer are shown in Table 4. The orientation degree of the nonwoven fabric of the filtration layer of Comparative Example 3 was completely isotropic.

[0430] A blood processing filter was prepared in the same manner as in Example 1. Table 4 shows the performance of the blood processing filter.

[0431] [Comparative Example 4]

[0432] The blood processing filter was prepared in the same manner as in Comparative Example 1 except that the direction of the filter layer in Comparative Example 1 was changed so that the ratio of Am:Ac was 1:1. The performance of the blood processing filter is shown in Table 4. It should be noted that in Comparative Example 4, blood with a higher viscosity and containing a relatively large amount of aggregates was used compared to the room temperature stored blood used in Comparative Example 1.

[0433] [Comparative Example 5]

[0434] The performance of the blood processing filter of Comparative Example 3 was evaluated using blood having a higher viscosity and containing a relatively large amount of aggregates than the room temperature stored blood used in Comparative Example 3. The results are shown in Table 4.

[0435] [Table 1]

[0436]

[0437] [Table 2]

[0438]

[0439] [Table 3]

[0440]

[0441] [Table 4]

[0442]

[0443] From the results of Examples 1 to 30 and Comparative Examples 1 to 5, it can be seen that by setting the maximum orientation ratio of the nonwoven fabric to 1.2 or more and then appropriately adjusting the ratio of Am to Ac in accordance with the properties of blood, a good filtration time or white blood cell count can be achieved compared to the case of using the nonwoven fabric of the comparison example with a more isotropic orientation ratio.

[0444] In particular, the results of Examples 21 to 30 show that nonwoven fabrics with a maximum orientation ratio of more than 1.2 can filter high-viscosity blood in a short time even if Am:Ac is set to 1:1, and the number of residual white blood cells can be reduced. This suggests that if the orientation ratio of the nonwoven fabric is high, a flow path for blood flow is formed, and even high-viscosity blood will not be blocked, and a constant flow rate is maintained, and as a result, the filtration time is shortened. In addition, it is shown that by preventing the flow path from being blocked, the effective utilization of the filter material is improved, and even for the number of residual white blood cells that is originally in a trade-off relationship, an improved effect is obtained compared with Comparative Example 4 (existing product).

[0445] Furthermore, in Examples 2 to 9, the number of residual leukocytes in the cold blood filtration was 5.5 Log or less, and the filtration time was 40 minutes or less, and the improvement of the preparation quality and the improvement of the workability were found to be accompanied by the improvement of the leukocyte removal ability. In particular, in Examples 2 to 6, the number of residual leukocytes was 5.3 Log or less, and the leukocyte removal ability was further improved.

[0446] Furthermore, in Examples 12 to 19, the number of residual leukocytes in room temperature blood filtration was 5.8 Log or less, and the filtration time was 40 minutes or less, and the improvement in the leukocyte removal ability was found to improve the quality of the preparation and the improvement in workability. In particular, in Examples 12 to 16, the filtration time was 35 minutes or less, and the workability was further improved.

[0447] Furthermore, for Examples 22 to 29, the number of residual leukocytes was 5.5 Log or less, and the filtration time was 40 minutes or less, and the improvement in the quality of the preparation and the improvement in the workability were found to be accompanied by the improvement in the leukocyte removal ability. In addition, for Examples 22 to 27, the filtration time was 30 minutes or less, and the work efficiency was further improved. In particular, for Examples 22 to 25, the number of residual leukocytes was 5.3 Log or less, and the leukocyte removal ability was further improved.

[0448] From the above results, it can be seen that for nonwoven fabrics with a maximum orientation ratio of 1.28 to 2.0, the filtration performance is further improved, and for nonwoven fabrics with a maximum orientation ratio of 1.28 to 1.42, the performance is further improved.

[0449] Next, a performance comparison by whole blood filtration was performed using an existing leukocyte removal filter or a filter layer manufactured by a manufacturing method described in a known document.

[0450] [Example 31]

[0451] (Manufacturing of blood treatment filters)

[0452] Fourteen sheets of the first filtration layer used in Example 1 were cut into 3 cm squares in such a manner that Am:Ac was 1.2:1 (the direction with a high degree of orientation was aligned with Am), and filled to an effective filtration area of ​​9 cm. 2 The blood processing filter is made by ultrasonic welding of a soft container. This is because the sizes of known filters vary, and in order to implement the method with uniform size, only small filters can be used for relative evaluation.

[0453] The blood processing filter was subjected to steam heating at 115° C. for 59 minutes and then vacuum dried at 40° C. for 15 hours or more. Table 5 shows the performance of the blood processing filter.

[0454] (Evaluation of leukocyte removal ability and filtration time)

[0455] As the blood used for the evaluation, whole blood was used as follows: 80 mL of blood immediately after blood collection was mixed with 11.2 mL of CPD solution as an anticoagulant, and the mixture was allowed to stand for 2 hours. Hereinafter, the blood prepared for the blood evaluation is referred to as pre-filtration blood.

[0456] However, in the blood transfusion market, blood stored at room temperature and blood stored under refrigeration are sometimes used, so this time the evaluation is based on both cases.

[0457] The blood bag filled with pre-filtration blood was connected to the inlet of the blood processing filter after steam heating treatment with a 40 cm tube made of vinyl chloride having an inner diameter of 3 mm and an outer diameter of 4.2 mm. Furthermore, the outlet of the blood processing filter was connected to the recovery blood bag with the same 85 cm tube made of vinyl chloride having an inner diameter of 3 mm and an outer diameter of 4.2 mm. Thereafter, the pre-filtration blood was flowed into the blood processing filter from the upper part of the blood bag filled with pre-filtration blood at a height of 140 cm, and the filtration time was measured until the amount of blood flowing into the recovery blood bag reached 0.2 g / min.

[0458] Furthermore, 3 mL of blood (hereinafter referred to as filtered blood) was recovered from the blood recovery bag. The leukocyte removal ability was evaluated by determining the number of residual leukocytes. The method for measuring the number of residual leukocytes was as described above.

[0459] In the above filter shape (14 sheets of non-woven fabric, effective filtration area 9cm 2 ), if the number of residual white blood cells is less than 5.3 Log / Bag for either room temperature stored blood or refrigerated stored blood and filtration can be completed within 45 minutes, it can be said that the filter element is an ideal white blood cell removal element in practical terms.

[0460] The number of residual white blood cells is preferably 5.12 Log / Bag or less, more preferably 4.95 Log / Bag or less, and even more preferably 4.77 Log / Bag or less. The filtration time is preferably within 40 minutes, more preferably within 35 minutes, and even more preferably within 30 minutes.

[0461] This filtration time value is the same as that of the normal filter size described in Examples 1 to 30. This is because the effective filtration area is 1 / 5 of that of the normal filter, and the amount of filtered blood is also 1 / 5, so the amount of blood flowing per unit area of ​​the filter material is the same. Therefore, the filtration time can be specified with the same time as that of the normal filter.

[0462] However, the number of residual white blood cells is less than 0.2×10 per bag because the blood volume is 1 / 5.6 (less than 5.3 Log / Bag), the standard deviation is approximately 0.18 Log, so the appropriate performance value changes. Table 5 shows the performance test results of the small blood processing filter.

[0463] [Comparative Examples 6 and 7]

[0464] eWBF3J manufactured by Haemonetics Corporation was disassembled, and a filter layer having an average fiber diameter of 1.6 to 1.8 μm and a relatively fine mesh was collected, and blood was filtered through a small filter in the same manner as in Example 31. However, the nonwoven fabric had a unit weight of 88 g / m 2 Therefore, in order to make the weight of the nonwoven fabric used in the filter uniform, 15 sheets of nonwoven fabric were stacked and used.

[0465] Since the maximum orientation ratio was 1.65, Am:Ac was stacked on the filter at 1.65:1 and 1:1.65, and evaluation was performed on each. The test results are shown in Table 5.

[0466] [Comparative Examples 8 and 9]

[0467] RZ-2000F manufactured by Asahi Kasei Medical Co., Ltd. was disassembled, and a fine-mesh filter layer having an average fiber diameter of 1.3 μm was collected, and blood was filtered through a small filter in the same manner as in Example 31. However, the nonwoven fabric had a unit weight of 40 g / m 2 Therefore, 32 sheets of nonwoven fabric are stacked and used.

[0468] Since the maximum orientation ratio was 1.13, Am:Ac was stacked on the filter in a ratio of 1.13:1 and 1:1.13, and evaluation was performed on each of them.

[0469] [Comparative Examples 10 to 13]

[0470] The leukocyte removal filter included in the Compoflow system manufactured by Fresenius Kabi was disassembled, and two filter layers with small average fiber diameters and different bulk densities were collected. Blood was filtered through a small filter using each filter layer in the same manner as in Example 31. However, the unit weight of the nonwoven fabric was 55 g / m 2 , 53g / m 2 Therefore, 23 and 24 nonwoven fabrics were stacked and used. The test results are shown in Table 5. The unit area weight was 55 g / m 2 The nonwoven fabric is described in Comparative Examples 10 and 11, and the weight per unit area is 53 g / m 2 The nonwoven fabric is described in Comparative Examples 12 and 13.

[0471] [Comparative Examples 14 and 15]

[0472] A nonwoven fabric described in Example 60 of Japanese Patent Table H10-508343 was produced. However, as manufacturing conditions not described in this example, the resin viscosity was set to 0.82 g / dL, the center-to-center distance between each nozzle was set to 0.1 cm, the nozzles were set to be arranged in a row of 200, and the inclination angle of the nozzles was set to 0 degrees. As a result, a nonwoven fabric having the properties described in the example was obtained, and blood was filtered through a small filter using the same method as in Example 31 of the present application. The unit weight of the nonwoven fabric was 54 g / m 2 Therefore, 24 sheets of nonwoven fabric were stacked and used. The test results are shown in Table 5.

[0473] [Comparative Examples 16 and 17]

[0474] The PBT nonwoven fabric described in Example 1 of International Publication No. 2018 / 034213 was used to filter blood through a small filter using the same method as Example 31 of the present application. The unit weight of the nonwoven fabric is 22 g / m 2 Therefore, 59 sheets of nonwoven fabric were used. The test results are shown in Table 5.

[0475] [Table 5]

[0476]

[0477] Next, the effect of forming the internal space of the nonwoven fabric was confirmed by the following test using an erythrocyte preparation that has a higher viscosity than whole blood and can detect the filtration time with higher accuracy.

[0478] (Leukocyte Removal Performance of Blood Treatment Filters)

[0479] As a blood product, 300 g of an erythrocyte product manufactured according to the European standard (the Guide to the Preparation, Use and Quality Assurance of Blood Components 19th edition (2017)) was used, and the blood treatment filters of the embodiments and comparative examples were used to filter and recover the blood product after filtration at a natural drop of 110 cm to obtain a blood product after filtration. Here, the drop refers to the distance from the bottom of the pre-filtration bag containing the erythrocyte product to the bottom of the post-filtration recovery bag of the erythrocyte product ( Figure 7 In the example above, the top plate of the balance).

[0480] Next, the number of remaining white blood cells was calculated according to the following calculation formula.

[0481] Residual leukocyte count = log[(leukocyte concentration in the blood product after filtration) × (blood recovery after filtration)]

[0482] The leukocyte concentration in the blood product before and after filtration was measured using a leukocyte count measurement kit "LeucoCOUNT" manufactured by Becton, Dickinson and Company (BD) and a flow cytometer FACS CantoII manufactured by BD.

[0483] [Evaluation criteria for the number of residual white blood cells]

[0484] ◎: Less than 5.0

[0485] ○: 5.0 or more and less than 5.5

[0486] ×: 5.5 or above

[0487] If the number of residual white blood cells per bag is less than 1×10 6 (less than 6Log / Bag) can prevent serious side effects in the same way as whole blood. However, it is known that in addition to the individual differences of whole blood, red blood cell preparations also have large differences in blood properties due to the deviations in craftsmanship during the manufacture of red blood cell preparations. When the same filter type is used, the standard deviation of the normal distribution of the number of residual white blood cells is about 0.30Log. In other words, if it is less than 5.0Log, the preparation can be made taking into account the high blood correlation ratio of more than 99.7%, which can dramatically suppress the risk of side effects of transfusion caused by the number of residual white blood cells. On the other hand, if it is less than 5.5Log, a correlation ratio of 90% is met, so it can be used in practice.

[0488] (Filter time)

[0489] In the aforementioned "(Leukocyte Removal Performance of Blood Treatment Filter)", the time (minutes) required from the start of the red blood cell preparation flowing through the blood treatment filter until the mass increase of the recovery bag of the red blood cell preparation after filtration stops is referred to as the filtration time (minutes). It should be noted that the stop of the mass increase of the recovery bag refers to the moment when the mass of the recovery bag is measured every 1 minute from the start of filtration and the mass change of the recovery bag is less than 0.1 g / minute. The final 1 minute for judging the stop of mass increase is included in the calculation of the filtration time.

[0490] [Evaluation criteria]

[0491] ◎: Less than 20 minutes

[0492] 0:20 minutes or more and less than 26 minutes

[0493] ×: 26 minutes or more

[0494] Based on the actual performance of a conventional leukocyte removal filter (Asahi Kasei Medical Co., Ltd. filter for erythrocyte preparation R-S11), the filtration time of an erythrocyte preparation needs to be less than 26 minutes in practical terms, and more preferably less than 20 minutes.

[0495] (Blood loss rate)

[0496] The recovery was terminated when the weight change of the recovery bag in 1 minute became less than 0.1 g, and the value of the balance at the end of the recovery was taken as the blood recovery amount. In addition, the blood loss rate was calculated by the following formula.

[0497] Blood loss rate (%) = 100 (%) × ((blood volume before filtration (g) - blood recovery volume (g)) / blood volume before filtration (g)

[0498] [Evaluation criteria]

[0499] ◎: Less than 8.0%

[0500] ○: 8.0% or more and less than 9.2%

[0501] ×: 9.2% or more

[0502] This time, the red blood cell preparation is combined into 300g for implementation, but there are individual differences in the amount of blood before filtration during actual use, so the amount of blood recovered needs to be calculated as the loss rate. If based on the actual performance of the existing leukocyte removal filter (AsahiKasei Medical Co., Ltd red blood cell preparation filter R-S11), the blood loss rate needs to be less than 9.2% in practice. And 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 given to the same patient can be reduced during blood transfusion, thereby achieving cost reduction and efficiency of operation in medical institutions.

[0503] [Example A1]

[0504] (Manufacturing of filter layer)

[0505] Polybutylene terephthalate (PBT) is spun by meltblowing to form a nonwoven fabric (fiber substrate). A rotary conveyor-type device is used for capture. As a meltblowing die, 10 meltblowing dies with a spinneret number of 10hole / cm and a die length (0.20m) of one tenth relative to the capture width (2m) of the capture conveyor are configured. A method of spinning from the end with a time difference in the width direction is adopted. The single hole ejection amount is set to 0.17 (g / (minute·hole)), the capture conveyor rotation speed is set to 220m / minute, the switching time of each spinneret is set to 4.1 seconds, and the ejection moving speed is set to 0.07m / second. Furthermore, it is adjusted in a manner that the distance (DCD) from the meltblowing die to the capture conveyor is 50mm. In addition, the die temperature during spinning is set to 280°C.

[0506] The obtained nonwoven fabric was coated with a hydrophilic polymer by the following method to obtain a nonwoven fabric having a coating layer (first filter layer). The nonwoven fabric was immersed in an ethanol solution of a hydrophilic polymer (concentration: 1.5 g / L), and the nonwoven fabric taken out from the polymer solution was pressed to remove the excess polymer solution absorbed, and the polymer solution was dried while feeding dry air to form a coating layer covering the outer peripheral surface of the nonwoven fabric.

[0507] The ratio of the amount of the basic nitrogen-containing functional groups in the peripheral surface portion (surface portion of the coating layer) of the obtained first filter layer to the total amount of the nonionic groups and the basic nitrogen-containing functional groups was 3.0 mol%, and the mass of the coating layer in 1 g of the first filter layer was 3 mg / g (fiber substrate+coating layer).

[0508] The various physical properties of the first filter layer are shown in Table 6. In addition, the variation of the in-plane porosity of the first filter layer in the thickness direction is shown in Table 6. Fig. 9 shown.

[0509] (Manufacturing of blood treatment filters)

[0510] As the second and third filter layers, use a unit area weight of 30 (g / m 2 ), air permeability resistance per unit area weight: 0.03 (kPa·s·m / g) of polyethylene terephthalate (hereinafter referred to as "PET") non-woven fabric.

[0511] From upstream to downstream of the blood flow, 4 sheets of the second filter layer, 16 sheets of the first filter layer, and 4 sheets of the third filter layer are stacked in order. The stacked body is sandwiched between two flexible vinyl chloride resin sheets having a port that serves as an inlet or outlet for blood, and the filter material and the surrounding part of the flexible sheet are welded and integrated using a high-frequency welding machine to produce a filter with an effective filtration area of ​​43 cm 2The blood processing filter was sterilized by high pressure steam at 115°C for 59 minutes, and then various performance tests were performed. The results are shown in Table 6.

[0512] [Example A2]

[0513] The first filter layer and the blood treatment filter were prepared in the same manner as in Example A1 except that the spinning width was changed to 1.6 m, 8 spinnerets were arranged in the width direction, and the spinneret switching time was adjusted so that the ejection moving speed was changed to 0.08 to 0.09 m / sec. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 6.

[0514] [Example A3]

[0515] The first filter layer and the blood treatment filter were prepared in the same manner as in Example A1 except that the spinning width was changed to 1.8 m, 9 spinnerets were arranged in the width direction, and the spinneret switching time was adjusted so that the ejection moving speed was changed to 0.07 to 0.08 m / sec. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 6.

[0516] [Example A4]

[0517] The first filter layer and the blood treatment filter were prepared in the same manner as in Example A1 except that the spinneret switching time was adjusted to change the ejection moving speed to 0.06-0.07 m / sec and the residence time was set to 15 seconds when the ejection area was repeated. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 6.

[0518] [Example A5]

[0519] The first filter layer and the blood treatment filter were prepared in the same manner as in Example A1 except that the spinneret switching time was adjusted so that the ejection moving speed was changed to 0.09 m / sec, the collection conveyor rotation speed was changed to 225-230 m / min, the meltblowing die length was changed to 0.40 m, and five spinnerets were arranged in the width direction. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 6.

[0520] [Examples A6 to A8]

[0521] The first filter layer and the blood processing filter were prepared in the same manner as in Example A1 except that the rotation speed of the collection conveyor was changed to 223-228 m / min in Example A6, 220-225 m / min in Example A7, and 215-220 m / min in Example A8. The physical properties of the first filter layer and the performance of the blood processing filter are shown in Table 6.

[0522] [Example A9]

[0523] The first filter layer and the blood treatment filter were prepared in the same manner as in Example A1 except that the spinneret switching time was adjusted so that the ejection moving speed was changed to 0.08-0.09 m / sec, the melt-blowing die length was changed to 0.40 m, and five spinnerets were arranged in the width direction. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 6.

[0524] [Example A10]

[0525] The first filter layer and the blood processing filter were prepared in the same manner as in Example A1 except that the spinneret switching time was adjusted so that the ejection moving speed was changed to 0.07-0.08 m / sec and the DCD was changed to 48-50 mm. The physical properties of the first filter layer and the performance of the blood processing filter are shown in Table 6.

[0526] [Example A11]

[0527] The first filter layer and the blood processing filter were prepared in the same manner as in Example A1 except that the spinneret switching time was adjusted so that the ejection moving speed was changed to 0.06-0.07 m / sec and the DCD was changed to 46-48 mm. The physical properties of the first filter layer and the performance of the blood processing filter are shown in Table 6.

[0528] [Example A12]

[0529] The first filter layer and the blood treatment filter were prepared in the same manner as in Example A1 except that the rotation speed of the collection conveyor was changed to 220 to 225 m / min and the DCD was changed to 58 to 60 mm. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 6. In addition, the variation of the in-plane porosity of the first filter layer in the thickness direction is shown in Table 6. Fig.10 shown.

[0530] [Example A13]

[0531] The first filter layer and the blood treatment filter were prepared in the same manner as in Example A1 except that the spinneret switching time was adjusted so that the ejection moving speed was changed to 0.06-0.07 m / sec, the collection conveyor rotation speed was changed to 220-225 m / min, the DCD was changed to 55-60 mm, the melt-blowing die length was changed to 0.153 m, and 13 spinnerets were arranged in the width direction. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 6.

[0532] [Example A14]

[0533] The first filter layer and the blood treatment filter were prepared in the same manner as in Example A1 except that the spinneret switching time was adjusted so that the ejection moving speed was changed to 0.06-0.07 m / sec, the collection conveyor rotation speed was changed to 225-230 m / min, the DCD was changed to 60-65 mm, the melt-blowing die length was changed to 0.153 m, and 13 spinnerets were arranged in the width direction. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 6.

[0534] [Examples A15 and A16]

[0535] The first filter layer and the blood treatment filter were prepared in the same manner as in Example A1 except that the spinneret switching time was adjusted so that the ejection moving speed was changed to 0.06-0.07 m / sec, and the collection conveyor rotation speed was changed to 225-228 m / min in Example A15 and to 220-225 m / min in Example A16. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 7.

[0536] [Example A17]

[0537] The first filter layer and the blood processing filter were prepared in the same manner as in Example A1 except that the spinneret switching time was adjusted so that the ejection moving speed was changed to 0.06 to 0.07 m / sec. The physical properties of the first filter layer and the performance of the blood processing filter are shown in Table 7.

[0538] [Examples A18 and A19]

[0539] The first filter layer and the blood processing filter were prepared in the same manner as in Example A1, except that the DCD was changed to 55-60 mm in Example A18 and to 40-45 mm in Example A19, and the single hole discharge rate was changed to 0.28 g / min / hole in Example A18 and to 0.18 g / min / hole in Example A19. The physical properties of the first filter layer and the performance of the blood processing filter are shown in Table 7.

[0540] [Examples A20 to A22]

[0541] The first filter layer and the blood processing filter were prepared in the same manner as in Example A1 except that the concentration of the hydrophilic polymer solution during coating was changed to 0.3 g / L in Example A20, 1.0 g / L in Example A21, and 5.0 g / L in Example A22. The physical properties of the first filter layer and the performance of the blood processing filter are shown in Table 7.

[0542] [Examples A23 and A24]

[0543] The first filter layer and the blood treatment filter were prepared in the same manner as in Example A1 except that the DCD was changed to 55 to 60 mm in Example A23 and to 45 to 50 mm in Example A24. It should be noted that the nonwoven fabric (fiber substrate) was pressurized at a weak pressure in Example A23 and at a strong pressure in Example A24 to adjust the filling rate. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 7.

[0544] [Comparative Example A1]

[0545] The first filter layer and the blood treatment filter were prepared in the same manner as in Example A1 except that the melt-blowing die length was changed to 0.3 m, the spinning width was changed to 0.3 m, and the ejection was not performed with a time difference. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 7. In addition, the variation of the in-plane porosity of the first filter layer in the thickness direction is shown in Table 7. Fig.11 shown.

[0546] [Comparative Example A2]

[0547] The first filter layer and the blood treatment filter were prepared in the same manner as in Comparative Example A1 except that the single hole ejection rate was changed to 0.24 g / min / hole. The physical properties of the first filter layer and the performance of the blood treatment filter are shown in Table 7. In addition, the variation of the in-plane porosity of the first filter layer in the thickness direction is shown in Table 7. Fig.12 shown.

[0548] [Comparative Example A3]

[0549] The first filter layer and the blood processing filter were prepared in the same manner as in Comparative Example A1 except that the single hole discharge rate was changed to 0.23 g / min / hole and the DCD was changed to 45 to 50 mm. Table 7 shows the properties of the first filter layer and the performance of the blood processing filter.

[0550] [Comparative Example A4]

[0551] As a collection device, a non-rotating belt conveyor type mesh was used, and spinning was performed while sucking under the mesh. PET resin was used, the single hole ejection amount was set to 0.08g / min / hole, DCD was adjusted at 50mm, the meltblowing die length was set to 0.3m, the spinning width was set to 0.3m, the belt conveyor moving speed was set to 0.05m / sec, and there was no time difference in ejection. The nonwoven fabric obtained was coated with a hydrophilic polymer using the same method as in Example A1 to form the first filter layer. The various physical properties of the first filter layer are shown in Table 7.

[0552] The obtained first filter layer was used to prepare a blood processing filter in the same manner as in Example A1. Table 7 shows various properties of the blood processing filter.

[0553] [Table 6]

[0554]

[0555] [Table 7]

[0556]

[0557] Industrial Applicability

[0558] By using a nonwoven fabric whose maximum orientation ratio is controlled to be above a certain level to make a filter, or using a filter layer having a predetermined space inside, the blood filtration time can be shortened and the number of residual white blood cells can be reduced. This has the advantages of improving the quality of blood in the blood transfusion market, shortening the time required for preparation production at the manufacturing site, and improving productivity, and is therefore considered to have industrial applicability.

[0559] Description of Reference Numerals

[0560] 1…container, 3…inlet, 4…outlet, 5…filter material, 7…side space of inlet, 8…side space of outlet, 9…outer edge of filter material, 10…blood processing filter, 11…first filter layer, 12…filtering direction, 13…plane direction orthogonal to the filtering direction, 14…plane direction parallel to the filtering direction, 15…blood flow (inlet), 16…blood flow (outlet), 17…maximum length in the plane direction, 18…maximum length in the thickness direction.

Claims

1. A leukocyte removal filter, comprising: a container having an inlet and an outlet for blood, and The filter material disposed between the inlet and the outlet in the container, The filter material comprises a filter layer, The filter layer comprises a nonwoven 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, that is, orientation degree X / orientation degree Y, is 1.2 or more.

2. The leukocyte removal filter according to claim 1, wherein The maximum value of the orientation degree X / orientation degree Y is 1.4 or more.

3. The leukocyte removal filter according to claim 1 or 2, wherein: The filter layer is configured as follows: the ratio of the orientation degree (Ac) of the fibers in the plane direction of the filter layer orthogonal to the filtering direction to the orientation degree (Am) of the fibers in the plane direction of the filter layer parallel to the filtering direction, i.e., Ac / Am, is greater than 1.

2.

4. The leukocyte removal filter according to claim 3, wherein Ac / Am is 1.4 or more.

5. The leukocyte removal filter according to claim 1 or 2, wherein The filter layer is configured as follows: the ratio of the orientation degree (Am) of the fibers in the plane direction of the filter layer parallel to the filtering direction to the orientation degree (Ac) of the fibers in the plane direction of the filter layer orthogonal to the filtering direction, i.e., Am / Ac, is greater than 1.

2.

6. The leukocyte removal filter according to claim 5, wherein Am / Ac is 1.4 or more.

7. The leukocyte removal filter according to any one of claims 1, 2, 4 and 6, wherein The non-woven fabric is a polyester non-woven fabric.

8. The leukocyte removal filter according to any one of claims 1, 2, 4 and 6, wherein The filter material comprises more than one filter layer.

9. The leukocyte removal filter according to any one of claims 1, 2, 4 and 6, wherein The nonwoven fabric comprises a fiber base material and a coating layer on the surface thereof.

10. The leukocyte removal filter according to claim 9, wherein When the total mass of the fiber base material and the coating layer is 1 g, the mass of the coating layer is 0.1 to 40.0 mg.

11. The leukocyte removal filter according to claim 8, wherein The nonwoven fabric has basic nitrogen-containing functional groups on its peripheral surface portion, that is, all portions of the nonwoven fabric exposed to the outside.

12. The leukocyte removal filter according to claim 11, wherein The nonwoven fabric also has nonionic hydrophilic groups on its peripheral surface portion.

13. The leukocyte removal filter according to claim 12, wherein The ratio of the amount of the basic nitrogen-containing functional groups in the peripheral surface portion of the nonwoven fabric to the total amount of the nonionic hydrophilic groups and the basic nitrogen-containing functional groups is 0.2 to 50.0 mol %.

14. The leukocyte removal filter according to claim 12, wherein The ratio of the amount of the basic nitrogen-containing functional groups in the peripheral surface portion of the nonwoven fabric to the total amount of the nonionic hydrophilic groups and the basic nitrogen-containing functional groups is 0.25 to 10 mol %.

15. The leukocyte removal filter according to claim 12, wherein The ratio of the amount of the basic nitrogen-containing functional groups in the peripheral surface portion of the nonwoven fabric to the total amount of the nonionic hydrophilic groups and the basic nitrogen-containing functional groups is 1 to 5 mol %.

16. The leukocyte removal filter according to claim 12, wherein The ratio of the amount of the basic nitrogen-containing functional groups in the peripheral surface portion of the nonwoven fabric to the total amount of the nonionic hydrophilic groups and the basic nitrogen-containing functional groups is 2 to 4 mol %.

17. The leukocyte removal filter according to claim 8, wherein The average fiber diameter of the nonwoven fabric is 0.3 μm to 3.0 μm.

18. The leukocyte removal filter according to claim 17, wherein The average fiber diameter of the nonwoven fabric is 0.5 μm to 2.5 μm.

19. A leukocyte removal filter comprising: a container having an inlet and an outlet for blood, and The filter material disposed between the inlet and the outlet in the container, The filter material comprises more than one filter layer, The filter layer has a space in a cross section in the thickness direction with a maximum length in the plane direction of 50 μm or more and a maximum length in the thickness direction of 15 μm or more; The maximum length in the plane direction and the maximum length in the thickness direction are determined as follows: (1) The sample of the filter layer photographed was 10 mm × 3 mm in size. The 10 mm side was used for cross-sectional observation, and three samples of 10 mm × 3 mm in size were used for measurement. At this time, the filter layer is cut in a way that the cross section of the sample is not crushed; if it is not broken, a fixing resin different from the fibers constituting the filter layer is poured between the fibers and solidified, and then the cross section is ground and observed; (2) The shooting magnification is set to a magnification that can observe the entire thickness of the filter layer; (3) For each sample, cross-section images were taken at three locations. The maximum length in the plane direction and the maximum length in the thickness direction were calculated using the aperture analysis software PHENOM POROMETRIC for the images obtained by the cross-section images. The average values ​​of the maximum length in the plane direction and the maximum length in the thickness direction of the nine points of each cross-section image were taken as the maximum length in the plane direction and the maximum length in the thickness direction of the sample.

20. The leukocyte removal filter according to claim 19, wherein The filling rate of the filter layer is 0.09 to 0.

26.

21. The leukocyte removal filter according to claim 19 or 20, wherein The filling rate of the filter layer is 0.12 to 0.

19.

22. The leukocyte removal filter according to claim 19 or 20, wherein The difference between the minimum porosity in the plane of the filter layer in the thickness direction and the maximum porosity in the plane of the filter layer in the thickness direction is 0.08 to 0.

28.

23. The leukocyte removal filter according to claim 22, wherein The difference between the minimum porosity in the plane of the filter layer in the thickness direction and the maximum porosity in the plane of the filter layer in the thickness direction is 0.10 to 0.

20.

24. The leukocyte removal filter according to claim 22, wherein The minimum porosity in the plane in the thickness direction is 0.72-0.85, and the maximum porosity in the plane in the thickness direction is 0.85-1.

00.

25. The leukocyte removal filter according to claim 22, wherein The minimum porosity in the plane in the thickness direction is 0.75 to 0.

83.

26. The leukocyte removal filter according to claim 22, wherein The maximum porosity in the plane in the thickness direction is 0.87 to 0.

95.

27. The leukocyte removal filter according to claim 19 or 20, wherein The specific surface area of ​​the filter layer is 0.50 to 1.50 m 2 / g.

28. The leukocyte removal filter according to claim 27, wherein The specific surface area of ​​the filter layer is 0.70 m 2 / g or above and 1.45m 2 / g or less.

29. The leukocyte removal filter according to claim 28, wherein The specific surface area of ​​the filter layer is 1.10 m 2 / g or more and 1.40m 2 / g or less.

30. The leukocyte removal filter according to claim 19 or 20, wherein The critical wet surface tension of the filter layer is 70-100 dyn / cm.

31. The leukocyte removal filter according to claim 19 or 20, wherein The nonwoven fabric contained in the filter layer has a fiber base material and a coating layer on the surface thereof.

32. The leukocyte removal filter according to claim 31, wherein When the total mass of the fiber base material and the coating layer is 1 g, the mass of the coating layer is 0.1 to 40.0 mg.

33. The leukocyte removal filter according to claim 31, wherein The nonwoven fabric contained in the filter layer has a basic nitrogen-containing functional group on its peripheral surface portion, that is, the entire portion of the nonwoven fabric exposed to the outside.

34. The leukocyte removal filter according to claim 33, wherein The nonwoven fabric contained in the filter layer also has nonionic hydrophilic groups on its peripheral surface portion.

35. The leukocyte removal filter according to claim 34, wherein The ratio of the amount of the basic nitrogen-containing functional groups in the peripheral surface portion of the nonwoven fabric to the total amount of the nonionic hydrophilic groups and the basic nitrogen-containing functional groups is 0.2 to 50.0 mol %.

36. The leukocyte removal filter according to claim 34, wherein The ratio of the amount of the basic nitrogen-containing functional groups in the peripheral surface portion of the nonwoven fabric to the total amount of the nonionic hydrophilic groups and the basic nitrogen-containing functional groups is 0.25 to 10 mol %.

37. The leukocyte removal filter according to claim 34, wherein The ratio of the amount of the basic nitrogen-containing functional groups in the peripheral surface portion of the nonwoven fabric to the total amount of the nonionic hydrophilic groups and the basic nitrogen-containing functional groups is 1 to 5 mol %.

38. The leukocyte removal filter according to claim 34, wherein The ratio of the amount of the basic nitrogen-containing functional groups in the peripheral surface portion of the nonwoven fabric to the total amount of the nonionic hydrophilic groups and the basic nitrogen-containing functional groups is 2 to 4 mol %.

39. The leukocyte removal filter according to claim 19 or 20, wherein The maximum length of the space in the plane direction is 50 μm to 2000 μm.

40. The leukocyte removal filter according to claim 39, wherein The maximum length of the space in the plane direction is 100 μm to 1500 μm.

41. The leukocyte removal filter according to claim 40, wherein The maximum length of the space in the plane direction is 200 μm to 1000 μm.

42. The leukocyte removal filter according to claim 41, wherein The maximum length of the space in the thickness direction is 15 μm to 200 μm.

43. The leukocyte removal filter according to claim 42, wherein The maximum length of the space in the thickness direction is 15 μm to 150 μm.

44. The leukocyte removal filter according to claim 43, wherein The maximum length of the space in the thickness direction is 20 μm to 100 μm.

45. The leukocyte removal filter according to claim 19 or 20, wherein The air permeability resistance of the filter layer is greater than or equal to 25 Pa·s·m / g and less than or equal to 100 Pa·s·m / g.

46. ​​The leukocyte removal filter according to claim 45, wherein The air permeability resistance of the filter layer is greater than or equal to 30 Pa·s·m / g and less than or equal to 90 Pa·s·m / g.

47. The leukocyte removal filter according to claim 46, wherein The air permeability resistance of the filter layer is greater than or equal to 40 Pa·s·m / g and less than or equal to 80 Pa·s·m / g.

48. A method for producing a blood product, comprising the step of allowing blood containing leukocytes to pass through the leukocyte removal filter according to any one of claims 1 to 47.

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