JPH06247862A - Leukocyte removing filter material, leukocyte removing device and method for removing leukocyte - Google Patents

Abstract

PURPOSE:To obtain a filter material having high leukocyte removing ability preferably useful for a filter device for removing leukocyte, being utilized in transfusing an erythrocyte preparation or whole blood preparation. CONSTITUTION:This leukocyte removing filter material comprises yarn or a porous material of a polymer having open pores, containing a basic functional group and a nonionic hydrophilic group and has a molar ratio of the basic functional group to the nonionic hydrophilic group on the surface of 0.6-6 and 5X10<-5> to 0.1meq/m<2> basic functional group density on the surface.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a leukocyte removing filter material, a leukocyte removing filter device and a leukocyte removing method. More specifically, the present invention relates to a filter material, a filter device and a method for removing contaminated white blood cells that cause side effects from a whole blood preparation for transfusion or a red blood cell preparation.

[0002]

2. Description of the Related Art In the field of blood transfusion, in addition to so-called whole blood transfusion, in which whole blood products obtained by adding an anticoagulant to blood collected from a blood donor are transfused, blood components required by the blood donor are obtained from the whole blood products. A so-called component blood transfusion in which the blood is separated and infused is generally performed. The component transfusion includes erythrocyte transfusion, platelet transfusion, plasma transfusion, etc. depending on the blood component required by the blood donor, and blood component preparations used for these include erythrocyte preparations, platelet preparations, plasma preparations and the like. In recent years, in these whole blood transfusions and component transfusions, so-called leukocyte-removing transfusions have been performed, in which contaminated leukocytes contained in blood products are removed and transfused. This is because the white blood cells mixed in the preparation are transfusion-related headache, nausea, chills, non-hemolytic fever reaction, alloantigen sensitization, post-transfusion GVH.
This is because it has become clear that it induces side effects such as D and virus infection.

In order to prevent relatively minor side effects such as headache, nausea, chills, and fever, it is necessary to suppress the number of white blood cells injected into a blood donor to 100 million or less in one blood transfusion. For this purpose, it is necessary to remove the number of leukocytes contaminated in the blood product until it becomes 10 ^-1 to 10 ^-2 or less. In addition, in order to prevent alloantigen sensitization, which is one of the serious side effects, it is said that it is necessary to suppress the number of leukocytes injected in one blood transfusion to 5 million or less than 1 million.
For this purpose, it is necessary to remove leukocytes in the preparation until the number of leukocytes becomes 10 ⁻⁴ or less. There is no established theory about post-transfusion GVHD and viral infection, but post-transfusion GVHD
For viruses that are thought to exist only in leukocytes, such as cytomegalovirus and adult T-cell leukemia virus, the number of leukocytes contaminated in the preparation is 10 ^-4 to 1
0 ^-6 By removing up to, and is expected to prevent onset and infection.

Methods for removing leukocytes from blood products are roughly classified into two types: a centrifugation method utilizing the difference in specific gravity of blood components and a filter method using a porous material having a fiber material or continuous pores as a filter material. Has a high leukocyte-removing capacity,
The filter method is widely used because of its simple operation and low cost.

It is considered that the main mechanism of leukocyte removal by the filter device using the above fiber material or porous material is that leukocytes in contact with the surface of the fiber or porous material are adsorbed on the surface of those materials. There is. A study of improving the performance of a conventional leukocyte removal filter device is mainly performed by increasing the frequency of contact between the surface of the filter material and leukocytes, that is, decreasing the average fiber diameter, increasing the packing density of the fibrous material, or making it more uniform. The focus is on using non-woven fabrics having various fiber diameter distributions (JP-A-2-203909). However, there is a limit to improving the performance of a preparation such as a red blood cell preparation or a whole blood preparation that contains a high proportion of red blood cells in the preparation by using only the above-mentioned means. That is, as the frequency of contact of white blood cells to the material is increased by the physical structure of the filter material as in the above method, the frequency of contact and passage resistance of the red blood cells present in a high concentration in the formulation to the surface of the filter material is also increased, and the treatment is performed. There have been problems such as a significant prolongation of time and hemolysis due to destruction of the red blood cell membrane. Therefore, when adopting the above-mentioned high performance method, considering the passage resistance of erythrocytes, naturally there is a range of the physical structure of the filter material that is acceptable, and the leukocyte-removing performance obtained with it. However, there are limits. Therefore, in order to prevent serious side effects such as alloantigen sensitization, post-transfusion GVHD, and virus infection, it is necessary to remove the number of contaminated leukocytes during the production to 10 ^-4 to 10 ^-6 or less, which results in a good treatment time. It was difficult to filter within the range.

On the other hand, considering the leukocyte removal mechanism (adsorption) as described above, it is considered possible to increase the adsorption probability of leukocytes with respect to the filter material by imparting appropriate chemical properties to the surface of the filter material. To be However, until now, in the study of leukocyte-removing filter materials for blood transfusion, few have attempted to increase the leukocyte-removing rate by paying attention to the chemical properties of the material surface.

[0007] As an example of examination focusing on the chemical properties of the material surface, Japanese Patent Laid-Open No. 1-249063, WO87 / 0581
2, EP0500472A2, Special Publication 3-502094
(WO89 / 03717). However,
The technique disclosed in Japanese Patent Laid-Open No. 1-249063 aims to selectively remove leukocytes from a platelet preparation for transfusion, while improving the passage rate of platelets, which are generally known as highly adsorbent cells. However, it merely discloses that, as the chemical properties of the material surface suitable for maintaining the adsorptivity of leukocytes, those having hydrophilicity and having no charge are useful. Similarly, WO87 / 05812 discloses a "selective removal of leukocytes" technique in which leukocytes are selectively adsorbed and removed, and platelets are not removed, but in the specification, "basic nitrogen-containing functional group" is disclosed. It was a general phenomenon that the material having a group becomes positively charged on the surface of the material in a physiological fluid in which cells are suspended and adheres well to negatively charged platelets and leukocytes. ", And to support this description,
In Examples and Comparative Examples using the surface-modified nonwoven fabric,
Experiments on fresh whole blood showed that leukocytes were removed to less than 10 ^{−2 as} the proportion of basic nitrogen-containing functional groups in the composition of the material constituting the peripheral surface of the fiber increased. Furthermore, the publication by the inventors of WO87 / 05812 (Advanced methods)
for leucocyte removal by
blood filtration. In: Brozo
vic B, ed. The Role of Leuc
octet Depletion in Blood
Transfusion Practice. oxfo
rd: Blackwell Scientific P
publication. 1989: 35-40. ) Also discloses experimental results with similar contents. However, when the filter materials described in these publications and documents were prepared and the blood products were actually filtered, as shown in Comparative Example 2 and Comparative Example 5 of the present application, the leukocyte removal expected in the erythrocyte products was expected. The rate improvement effect was not obtained. In addition, in both cases of whole blood preparations and red blood cell preparations, it was not possible to remove the number of leukocytes contaminated in the preparation to 10 ⁻⁴ to 10 ⁻⁶ or less. Furthermore, the leukocyte removal rate does not necessarily increase in proportion to the ratio of the functional groups, and even if the leukocyte removal rate is high, the leukocyte removal rate is higher than that of the material having no such functional groups. It even dropped.

[0008] Further, EPO500472A2 is intended to enhance the removal rate of platelets while maintaining good permeability of red blood cells by using a filter material having a positive zeta potential in removing white blood cells and platelets from a red blood cell preparation. It is a technology and is not intended to increase the leukocyte removal rate. There is a description in the specification that leukocytes can be satisfactorily removed even if the surface modification technology disclosed herein is not applied. Needless to say, specific requirements for increasing the leukocyte removal rate (for example, the present application). The ratio of the basic functional group to the nonionic functional group and the density of the basic functional group, which are disclosed in (1), are not specifically described. In fact, even when the examples and the comparative examples are compared, there is no clear indication that the leukocyte removal rate is increased by this technique, and conversely, there are also cases where the leukocyte removal rate is decreased. In Example 6, with a polyurethane sponge coated with a coating material having a quaternary ammonium salt,
It has been shown that the white blood cells in the red blood cell preparation were removed up to 10 ^−3.7, but there is no example in which they were removed up to 10 ⁻⁴ to 10 ⁻⁶ or less. Further, as for the base material for the filter material, only Egyptian cotton, polyvinyl formal porous body and polyurethane porous body are disclosed, and it is widely used as a suitable filter material or a base material for the filter material. There is no specific detailed description about the materials and forms other than the above, including the nonwoven fabric made of synthetic fibers. In addition, quaternary ammonium salts are widely known to have antibacterial properties, but their action is believed to be brought about by the destruction of bacterial cell membranes by quaternary ammonium salts (Tomiki Ikeda )other,
"Antibacterial polycation". Kiichi Takemoto et al., Polymers and Medicine, pages 459-496, Mita Press, 1989
Year). Therefore, the red blood cell membrane is very likely to be damaged, and there is a problem in safety and effectiveness as a blood transfusion filter.

Further, Japanese Patent Publication No. 3-502094 (WO89 /
No. 03717) is intended to impart hydrophilicity to the filter material to facilitate priming with blood, not to enhance the leukocyte removal rate. In fact, there is no description that the leukocyte adsorption probability is improved by the surface modification technology disclosed here. These known techniques have no viewpoint of increasing the adsorption probability of leukocytes to the filter material by imparting appropriate chemical properties to the surface of the filter material, and therefore, they are provided as materials for increasing the leukocyte removal rate. There was no description of the chemical properties that should be used. Further, there was hardly any description showing that the leukocyte removal rate was improved by these techniques.

[0010]

As described above, in the leukocyte-removing filter material for blood transfusion, it has a remarkable effect of improving the adsorbing power of leukocytes, and has a leukocyte count of 10 ^-4 to 10 in whole blood and erythrocyte preparations. ^-There is no serious reference to the chemical properties of the surface of the material necessary and sufficient to remove it to ^-6 or less, and it is necessary to use a large amount of filter material to achieve the above target. It was Therefore, if you try to maintain a good flow rate during filtration,
Since the density of the filter material has to be reduced, the volume of the filter device becomes large, and the amount of blood to be discarded together with the filter device generally increases, resulting in a low red blood cell recovery rate. In this case, the packing density of the filter material in the filter device must be increased, and therefore, the low flow rate during blood processing and its marked decrease with time have to be tolerated.

[0011]

The first object of the present invention is to:
To provide a filter material having a high leukocyte-removing ability, which can be suitably used for a leukocyte-removing filter device used in transfusing a red blood cell preparation or a whole blood preparation, more specifically, a certain chemical property on the surface of the filter material. The present invention provides an excellent filter material capable of removing leukocytes to 10 ⁻⁴ to 10 ⁻⁶ or less and simultaneously achieving a red blood cell recovery rate of 90% or more and a good treatment time. A second object of the present invention is to provide a leukocyte-removing filter device having a high leukocyte-removing ability for a red blood cell preparation or a whole blood preparation, and more specifically, to appropriately filter a filter material provided with a certain chemical property. By placing it in the device, 10
It is to provide an excellent filter device capable of removing ^-4 to 10 ^-6 or less. A third object of the present invention is to provide a leukocyte removal method capable of achieving a high leukocyte removal rate when transfusing a red blood cell preparation or a whole blood preparation, more specifically, a filter material having a certain chemical property. Another object of the present invention is to provide a leukocyte removal method capable of removing leukocytes up to 10 ⁻⁴ to 10 ⁻⁶ or less by filtering the above blood product using the above method.

According to the above object, the present inventors have studied earnestly on the kind of charge to be introduced and the amount thereof introduced, considering the improvement of the leukocyte adsorption force by introducing the charge to the surface of the filter material. Non-woven fabrics and polymer porous materials obtained by directly polymerizing a polymerizable monomer having various basic functional groups having positive charges on the fiber surface by a radiation grafting method, or a polymer obtained by polymerizing the monomer, on the fiber surface. The leukocyte removal performance of these non-woven fabrics and polymer porous bodies was investigated using a non-woven fabric and a polymer porous body. Surprisingly, these non-woven fabrics or polymer porous bodies had a high content of basic nitrogen atoms on their surface. It was found that the leukocyte-removing performance is not improved or rather deteriorates in some cases. Therefore, as a result of further investigation from the viewpoint of the chemical properties of the surface of the material that the basic functional group may have a remarkable or improving effect on the adsorption of leukocytes, surprisingly, the material having the basic functional group In order for the surface to have a high leukocyte-removing performance, the material surface must contain basic functional groups and nonionic hydrophilic groups in an optimal range ratio, and the basic functional group density on the material surface is suitable. The inventors have found that they need to be controlled within a range, and have completed the present invention.

That is, the present invention has a basic functional group and a nonionic hydrophilic group on the surface, and the molar ratio of the basic functional group to the nonionic hydrophilic group on the surface is in the range of 0.6 to 6. And basic functional group is 5 × 10 ^{−5 to} 0.1 meq
A filter material for removing leukocytes from whole blood or red blood cell preparations, comprising a polymeric porous body having fibers or continuous pores, characterized by being present on the surface at a density of / m ² / A leukocyte-removing filter device in which a leukocyte-removing filter material composed of a polymeric porous material having fibers and / or continuous pores is filled in a container having an outlet, and the blood inlet and outlet are separated by the material. Part or all of the material has a basic functional group and a nonionic hydrophilic group on the surface, and the molar ratio of the basic functional group to the nonionic hydrophilic group on the surface is in the range of 0.6 to 6. And the basic functional group is 5 ×
A leukocyte-removing filter device, which is a filter material present on the surface at a density of 10 ^{−5 to} 0.1 meq / m ² , and a preparation for removing leukocytes from a whole blood preparation for transfusion or a red blood cell preparation. Having a basic functional group and a nonionic hydrophilic group on the surface, and the molar ratio of the basic functional group to the nonionic hydrophilic group on the surface is 0.6.
To 6 and the basic functional group is 5 × 10 ⁻⁵
A method for removing leukocytes, which comprises filtering using a filter material which is present on the surface at a density of 0.1 meq / m ^{2 and} is composed of a polymer or a porous polymer having continuous pores.

In the filter material of the present invention, the surface of the material has a basic functional group and a nonionic hydrophilic group, and the nonionic hydrophilic group of the basic functional group contained in the surface portion is used. It is necessary that the molar ratio is 0.6 to 6. When the basic functional group content is less than 0.6 times the nonionic hydrophilic group content, sufficient leukocyte removal performance cannot be obtained, and the basic functional group content is 6% of the nonionic hydrophilic group content. When the amount is more than twice the molar amount, the reason is not always clear, but it is not suitable because the sufficient effect of improving leukocyte removal performance may not be obtained. More preferable ratio of basic functional group content to nonionic hydrophilic group is 0.6.
˜4.0, and more preferably 0.7 to 2.5. In the present invention, the basic functional group means an amino group such as a primary amino group, a secondary amino group or a tertiary amino group,
A nitrogen-containing aromatic ring group such as a pyridyl group or an imidazolyl group. Among these, an amino group is a preferable functional group in terms of high safety as a medical device, and a tertiary amino group is more preferable.

In the present invention, the nonionic hydrophilic group means hydroxyl group, amide group, ether group, nitro group, nitroso group, sulfoxide group, sulfonyl group, phosphoryl group, phospho group, carboxamide, sulfonamide, thioacid amide. , A cyano group, a cyanate, a thiocyanate, an isocyanate, an isothiocyanate, a thiocarboxylic acid, etc., and a polyethylene oxide chain composed of repeating ethylene oxide units among hydroxyl groups, amide groups and ethers having high hydrophilicity is preferable. However, regarding a polyethylene oxide chain, one polyethylene oxide chain is counted as one functional group regardless of the number of repeating ethylene oxide units, that is, regardless of the length of the polyethylene oxide chain. When the polyethylene oxide chains contained in the material are not uniform in chain length, the number average chain length of the polyethylene oxide chains is determined, and the number of ethylene oxide units contained in the average chain length is counted as one functional group.

In the present invention, the density of the basic functional groups contained on the surface of the filter material is 5 × 10 ^{-5 to} 0.
It is necessary to be 1 meq / m ² . When the density of basic functional groups on the surface of the filter material is less than 10 ⁻⁵ ,
Even if the ratio of the basic functional group to the nonionic hydrophilic group is within the optimum range, it is not suitable because a sufficient leukocyte removal rate improving effect cannot be obtained. On the other hand, if it exceeds 0.1 meq / m ² , the red blood cells tend to be damaged, which is not suitable. The preferred basic functional group density on the surface of the material is 10
^{-4 to} 5 × 10 ^-2 meq / m ² , more preferably 5
× 10 ⁻⁴ to 1 × 10 ⁻² meq / m ² .

The ratio of the basic functional group contained on the surface of the material to the nonionic hydrophilic group is X-ray photoelectron spectroscopy (XPS), Auger electron spectroscopy (AES), secondary ion mass spectrometry (SIMS). , Multi-total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and other known methods. Alternatively, the surface of the material may be extracted by an appropriate method, and the ratio of the functional groups of the extracted substance may be analyzed by the above-mentioned known method, nuclear magnetic resonance spectroscopy (NMR) or the like. The amount of basic functional group can also be determined from the amount of acidic dye such as trypan blue adsorbed or acid-base titration. In addition, the basic functional group density on the material surface in the present invention means a value obtained by the following method. First, the amount of surface basic functional groups per unit weight of the filter material is measured using any of the above methods. Next, the total pore surface area per unit weight is measured using a mercury porosimetry method, and the surface basic functional group amount per material unit weight is divided by this value, and the surface basic functional group amount per material unit surface area, That is, the basic functional group surface density is calculated.

The total pore surface area per unit weight of the filter material is measured by the mercury penetration method by the following method.
A part of the filter material is sampled and its weight (W) is measured. 0.1 to 1 with a mercury porosimeter (Poresizer 9310 PC2A type, Shimadzu Corporation, Kyoto, Japan or equivalent model) for the sample.
The total pore surface area (A) is measured in the pressure range of 80 psia, and the total pore surface area per unit weight is calculated from the following formula. Total pore surface area per unit weight = A / W When determining the total pore surface area per unit weight, three or more points of the filter material are sampled,
It is preferable to obtain the average value, but as a result of measuring a plurality of points, a part of the points falls within the range specified in the present invention,
If the remaining portions deviate from the range, such materials should be considered to be within the scope of this patent.

The basic functional group and the nonionic hydrophilic group in the present invention may be the basic functional group and the nonionic hydrophilic group possessed by the polymer itself which constitutes the filter material. Sharing monomers, polymers, etc., having a basic functional group and a nonionic hydrophilic group with a filter material that does not have a nonionic hydrophilic group or both functional groups (hereinafter referred to as a filter material substrate or simply a substrate) It may be introduced by fixing using any known method such as binding, ionic binding, physical adsorption, embedding or precipitation insolubilization of the material on the surface of the substrate, but graft polymerization method such as radiation grafting or plasma grafting. And a method for directly graft-polymerizing a monomer having a basic functional group and a monomer having a nonionic hydrophilic group onto the surface of a substrate, That the method of coating a polymer having a nonionic hydrophilic group and a functional group on the substrate surface is relatively easy to manufacture, and preferred since the excellent stability of performance. In the case of polymer coating, the polymer may be crosslinked after coating in order to prevent the polymer from falling off the substrate.

To give an example of a substance which can be immobilized on the surface of a substrate for a filter material by these preferable methods, a substance having a basic functional group which can be immobilized by a graft polymerization method is dimethylaminoethyl (meth). Acrylate, diethylaminoethyl (meth) acrylate, dimethylaminopropyl (meth) acrylate, 3
-Derivatives of (meth) acrylic acid such as dimethylamino-2-hydroxypropyl (meth) acrylate, styrene derivatives such as p-dimethylaminomethylstyrene, p-diethylaminoethylstyrene, 2-vinylpyridine, 4-vinylpyridine, 4 -Vinyl derivatives of nitrogen-containing aromatic compounds such as vinyl imidazole. Among the above substances, derivatives of (meth) acrylic acid such as dimethylaminoethyl (meth) acrylate and diethylaminoethyl (meth) acrylate are preferably used because they are easily available and easy to handle during graft polymerization.

Examples of the substance having a nonionic hydrophilic group which can be immobilized by the graft polymerization method are 2-hydroxyl ethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate and glycerin mono (meth).
Derivatives of (meth) acrylic acid such as acrylates, those having hydroxyl groups such as vinyl acetate (after polymerization and hydrolyzing to vinyl alcohol), those having amide groups such as (meth) acrylamide and N-vinylpyrrolidone In addition, as a monomer having a polyethylene glycol chain, methoxytriethylene glycol (meth) acrylate, methoxynonaethylene glycol (meth)
Examples thereof include acrylate and octaethylene glycol (meth) acrylate. Furthermore, examples of the substance having both a nonionic hydrophilic group and a basic functional group include substances having an epoxy ring, for example, substances having a primary or secondary amino group such as dimethylamine in glycidyl (meth) acrylate. And the like.

As the substance which can be fixed by coating, at least one kind of the above-mentioned monomer having a basic functional group (hereinafter simply referred to as basic monomer) and a monomer having a nonionic hydrophilic group (hereinafter simply referred to as hydrophilic). A copolymer obtained by polymerizing one or more kinds of monomers, and one or more kinds of these basic monomers and one or more kinds of hydrophilic monomers, and an ionically neutral nonionic hydrophilic group. A copolymer obtained by polymerizing one or more kinds of polymerizable monomers (hereinafter, simply referred to as neutral monomers) and / or one or more polymerizable monomers having an acidic functional group (hereinafter, simply referred to as acidic monomers) Is mentioned. Furthermore, a homopolymer of a monomer having both a nonionic hydrophilic group and a basic functional group (hereinafter, simply referred to as hydrophilic and basic monomer) or a copolymer obtained by polymerizing two or more hydrophilic and basic monomers Copolymer obtained by polymerizing a polymer or one or more kinds of hydrophilic and basic monomers and one or more kinds of monomers arbitrarily selected from a basic monomer, a hydrophilic monomer, a neutral monomer and an acidic monomer There are coalesces. When polymerizing these monomers, a random copolymerization method,
Any known method such as a block copolymerization method, an alternating copolymerization method, or a method in which a part of a monomer is previously polymerized to form a macromonomer and then the macromonomer and the monomer are copolymerized can be used. The random copolymerization method is particularly preferable because it is easy to handle.

Examples of the neutral monomer used here include those having a vinyl group such as styrene and methyl (meth) acrylate, and those having an acetylene group, and the acidic monomer includes a carboxyl group such as methacrylic acid. Those having a sulfonic acid group such as styrene sulfonic acid, mono (2- (meth) acryloyloxyethyl) acid phosphate, mono (2
Examples thereof include those having a phosphoric acid group such as-(meth) acryloyloxybutyl) acid phosphate.

A method of blending and coating the (co) polymer obtained by polymerizing the above basic monomer and the (co) polymer obtained by polymerizing the hydrophilic monomer may be adopted. . Further, a base material for a filter material is coated with a polymer obtained by polymerizing a substance having an epoxy ring, for example, glycidyl (meth) acrylate, which has a primary or secondary amino group such as dimethylamine. A method of reacting a substance to induce a basic functional group and a nonionic hydrophilic group may be adopted.

The filter material or the base material for the filter material in the present invention is a non-woven fabric prepared by a melt blow method, a flash spinning method or a papermaking method,
It may be in any form of a known filter material such as paper, woven fabric, mesh and porous body, but non-woven fabric is a particularly suitable form. Here, the non-woven fabric refers to a cloth-like one in which fibers or an aggregate of fibers are chemically, thermally, or mechanically bonded to each other without depending on the knitting or weaving. When the fibers have a certain shape due to friction caused by the fibers coming into contact with each other or by being entangled with each other, they are included in the mechanically bonded state.

When the base material for the filter material is composed of fibers, examples of the fiber material are polyamide, aromatic polyamide, polyester, polyacrylonitrile, polytrifluorochloroethylene, polymethylmethacrylate, polystyrene and polyethylene. , Synthetic fibers such as polypropylene, regenerated fibers such as cellulose acetate, cupraammonium rayon and viscose rayon, and natural fibers such as hemp, cotton, silk and wool fibers, which have the following preferable properties for the present invention. Synthetic fiber is a more preferable material because of the ease of manufacturing when forming the resin. Among these, polyester, polyethylene and polypropylene are more preferable.

In the present invention, when the filter material is made of fibers, the average fiber diameter of the fiber filter element made of these fibers is preferably 0.3 to 5 μm, more preferably 0.3 to 3.5 μm. Is more preferable, and further preferably 0.5 to 2.5 μm. This is because if the average fiber diameter is less than 0.3 μm, the pressure loss during filtration of the red blood cell product or the whole blood product is too high, which may impractically destroy the red blood cells, while the average fiber diameter If it exceeds 5 μm, the frequency of contact between leukocytes and the fiber surface is too low, and the effects of the invention may not be sufficiently exhibited.

The average fiber diameter referred to in the present invention is a value obtained by the following procedure. That is, a part of the fiber filter element, which is recognized as being substantially uniform, is sampled from one or a plurality of non-woven fabrics, woven fabrics, papers and meshes constituting the filter material, and photographed using a scanning electron microscope or the like. At the time of sampling, the fiber filter element is divided into squares each having a side of 0.5 cm, and six points are randomly sampled from the square. Of the 6 sections sampled, 3 sections are surfaces assumed to be disposed on the blood inlet side when filling the inside of the filter device (for convenience, hereinafter referred to as a-plane), and the remaining 3 sections are blood. The center portion of a surface supposed to be arranged on the exit side of the sheet (for convenience, referred to as surface b below) is photographed at a magnification of 2500 times. A photograph is taken for each sampled section, and when the total number of fibers taken in the photograph exceeds 100, the photograph ends. The diameter of all the fibers in the photograph thus obtained is measured. The diameter here means the width of the fiber in the direction perpendicular to the fiber axis. The value obtained by dividing the sum of all measured fiber diameters by the number of measured fibers is taken as the average diameter. However, if multiple fibers are overlapped and the width cannot be measured due to the shadow of other fibers, or if multiple fibers become thick due to melting etc., fibers with significantly different fiber diameters In the case of mixed cases, etc., these data are deleted. Further, in the measured fiber filter element, when there is a statistically significant difference between the fiber diameters of the a-face and the b-face, this is no longer recognized as the same fiber filter element. In this case, the a-face side and the b-face side are different fiber filter elements. Here, the fiber filter element is composed of one or a plurality of fiber cloth layers made of non-woven fabric, woven cloth, paper, mesh, etc., and each average fiber diameter of the fiber cloth layers is the same as that of the whole plural fiber cloth layers. A fiber cloth structure having substantially the same average fiber diameter. The F value of the fiber filter element is preferably 1.6 to 10 g / sec / m, more preferably 2.6 to 8 g / sec / m, and 2.4 to 6 g / sec / m. Is more preferable. Here, the F value means Japanese Industrial Standard JISL-109.
Ventilation amount of the fiber filter element measured by the test specified in 6, that is, the amount of air passing through the element in 1 second when a differential pressure of 12.7 mmAq is provided on the front and back surfaces of the fiber filter element at 20 ° C. Value per 1 cm ^{2 of the device} (unit = L / sec / cm ² ) and 1 of the device
cm refers to the 100 of the value obtained by multiplying the ² per weight, ie the mass per unit area (unit = g / cm ^2). When the F value is less than 1.6, the passage resistance of blood increases and a sufficient flow rate cannot be obtained, or the flow rate decreases with time due to blood treatment, and the tendency is not suitable for practical use, which is not preferable. Also, the F value is 1
When it exceeds 0, the frequency of contact between leukocytes and the filter material is low, and the leukocyte removal rate tends to be low, which is not preferable.

When the container is filled with the filter material of the present invention made of fibers and used as a leukocyte removal filter device, the packing density is 0.08 to 0.4 g / cm ^3.
Is more preferable, 0.1 to 0.35 g / cm ³ is more preferable, and 0.15 to 0.3 g / c is further preferable.
It is more preferably m ³ . If it is less than 0.08 g / cm ^3, the gap between the fibers is too large, so that the frequency of contact of leukocytes with the fiber surface may be reduced and the effect of the present invention may not be sufficiently obtained, which is not preferable. 0.4 g /
If it exceeds cm ³ , the gap between the fibers becomes too small, and the pressure loss at the time of passage of red blood cells increases, which is not practical, which is not preferable. Here, the packing density is a value obtained by dividing the weight of the filter material in the effective filtration area portion stored in the container by the (effective filtration area × thickness).
The P value of the leukocyte removal filter device is 3 to 50 m.
mAq / g is preferable, and 7-40 mmAq /
More preferably g, 13-30 mmAq / g
Is more preferable. Here, the P value is a value obtained by dividing the ventilation pressure loss of the leukocyte removal filter device by the weight of the filter material having an average fiber diameter of 0.3 to 5 μm in the effective filtration cross section of the device. The ventilation pressure loss is a value measured by the following method. Dry air is caused to flow from the blood inlet side to the blood outlet side of the filter device at room temperature at a constant flow rate of 3 L / min, and the pressure loss in the filter device is measured. When the P value is less than 3, the leukocyte removal rate tends to decrease, and when it exceeds 50, the treatment time tends to be prolonged, which is not preferable.

When the filter material or the base material for the filter material is a polymer porous body having continuous pores,
Examples of the material of the porous material substrate include polyacrylonitrile, polysulfone, cellulose, cellulose acetate, polyvinyl acetal, polyester, poly (meth) acrylate and the like.

The polymeric porous material used as the filter material in the present invention has an average pore diameter of 1 to 60 μm.
Is preferable, 1 to 30 μm is more preferable, and 1 to 20 μm is further preferable. If the average pore size is less than 1 μm, it may be difficult for red blood cells to pass therethrough, and if it exceeds 60 μm, the contact frequency between the surface of the porous body and leukocytes is too low, and the effect of the present invention is not sufficiently exerted. There is a fear that it is not preferable.

The average porosity of the polymer porous body is 45
˜95% is preferable, 70 to 95% is more preferable, and 80 to 95% is further preferable. If the average porosity is less than 45%, it may not be possible to provide a sufficient space for the passage of red blood cells. Absent.

In the present invention, the average porosity and average pore size are determined by the mercury porosimetry method described below.
From a porous filter element constituting the filter material, three areas were randomly sampled at a constant area (S), and the thickness (t) of each was measured using a Peacock thickness meter,
From these values, the apparent volume of each sample (V ₁ = S ×
T) is calculated. 0.1-180 ps for each sample
The total pore volume (V ₂ ) and the total pore surface area (A) measured in the pressure range of ia are determined. Using these values, the porosity is calculated from the following formula, and the average pore diameter is calculated from the formula. Porosity = (V ₂ / V ₁ ) × 100 (%) ……………………………………………………………………………………………………………… obtain the average value of the porosity at three points and use this as the average porosity of the porous body. Average pore diameter = (4 × V ₂ ) / A ... The average value of the average pore diameters at three locations is determined, and this is set as the average pore diameter of the porous body. Here, the porous body element is composed of one layer or a plurality of layers of a polymer porous body having continuous pores, and the average pore diameter and the average porosity of the porous body layer are the plurality of porous body layers. It is a porous structure having substantially the same average porosity and average porosity as a whole.

In the present invention, the pure water wetting time of the filter material composed of the polymer or the porous polymer having continuous pores is preferably less than 40 seconds, more preferably less than 30 seconds, and more preferably 10 seconds. The following is more preferable. When the wet time of pure water is 40 seconds or more, the wettability of the filter material is low with respect to plasma having almost the same surface tension as pure water. It is not preferable because it may disturb the blood flow. The pure water wetting time here is a value obtained by the following procedure. That is,
10 μl of distilled water is dropped on the surface of the material to be measured, and the time immediately after the dropping until the water droplet is wet absorbed by the material is measured. This test is repeated 5 times, the average value of these measured values is obtained, and it is defined as the pure water wetting time of the material.

When a filter material composed of a polymer and / or a polymer porous material having continuous pores is filled in a container and used as a leukocyte removal filter device, a fiber having an average fiber diameter of 0.3 to 5 μm is used. And / or the total thickness of the filter material made of a porous material having an average pore size of 1 to 60 μm is 1 to 10
mm is preferred, 2-8 mm is more preferred, and 3-6 mm is even more preferred. If it is less than 1 mm, a sufficient leukocyte removal rate tends not to be obtained, and if it exceeds 10 mm, the treatment time tends to be prolonged.

The filter device of the present invention comprising fibers comprises:
It is preferable that the fiber filter elements having a smaller average fiber diameter are sequentially arranged from the blood inlet side to the blood outlet side, and in particular, one of the elements is located closer to the blood inlet than the element having the smallest average fiber diameter. 2 times or more and 5 μm
It is preferred that a filter element having the following average fiber diameter is arranged. The element with the smallest average fiber diameter is the element with the best leukocyte adsorption efficiency. It is preferable to roughly remove leukocytes by the element.

In the filter device of the present invention, the effective filtration area / filter thickness is preferably 50 to 300, more preferably 70 to 250, and 90 to 2
It is more preferably 00. Here, the filter thickness means the thickness of a filter material made of fibers having an average fiber diameter of 0.3 to 5 μm and / or a polymer porous material having an average pore diameter of 1 to 30 μm in a filter device, that is, a filter. The shortest distance that blood can flow through the material. If the effective filtration area / thickness is less than 50, the flow rate and the leukocyte removal rate decrease with time during blood treatment, which is stable when treating various blood products having different numbers of microaggregates and leukocytes. It is not preferable because it tends to be difficult to exert the performance.
On the other hand, if the effective filtration area / thickness exceeds 300, the allowable filter thickness is too small to achieve a red blood cell recovery rate of 90% or more, and the white blood cell residual rate is 10 ⁻⁴ to 10 ^−10.
It is not preferable because it becomes difficult to fill the filter material in an amount necessary to achieve ^-6 , and it tends to be difficult to stably manufacture the filter material.

The leukocyte-removing filter device and leukocyte-removing method of the present invention include a filter material composed of fibers having an average fiber diameter of 0.3 to 5 μm and / or an average pore diameter of 1 to 3.
The treated blood volume per 1 g of the weight of the filter material composed of a 0 μm polymer porous body is preferably 0.1 to 0.5 unit, and more preferably 0.15 to 0.45 unit. Here, 1 unit of the treated blood volume is 500 m
Whole blood preparation obtained by adding a necessary amount of anticoagulant to blood of L, or red blood cell preparation obtained by removing platelet poor plasma, platelet rich plasma, buffy coat, etc. from the whole blood preparation by a method such as centrifugation. Furthermore, after removing platelet poor plasma, platelet rich plasma, buffy coat and the like from whole blood products by a method such as centrifugation, SAGM, Adsol, Neutr
An erythrocyte preparation obtained by adding an erythrocyte preservation solution such as icell or MAP. If it is less than 0.1 unit, the red blood cell recovery rate tends to decrease because much blood is discarded together with the filter material or the filter device.
If it exceeds 5 units, the leukocyte removal rate and the flow rate tend to be low, which is not preferable.

[0039]

EXAMPLES The present invention will be described in more detail with reference to examples. The treatment time was 25 minutes or less in all the examples, and a good flow rate could be maintained.

[0040]

Example 1 0.4 mol / mL of dimethylaminoethyl methacrylate (hereinafter abbreviated as DM) in special grade ethanol.
L, 2-hydroxyethyl methacrylate (hereinafter HE
(Abbreviated as MA) was added to a concentration of 0.6 mol / L, and the total amount was 250 ml. V-6 as a polymerization initiator
5 was added so as to have a concentration of 0.01 mol / L, polymerization was carried out at 45 ° C. for 4.5 hours in a nitrogen atmosphere, and then the substance precipitated by dropping in distilled water was collected and freeze-dried. And HE
A copolymer with MA was obtained. A polyester nonwoven fabric having an average fiber diameter of 1.8 μm manufactured by a melt-blowing method has a packing density of 0.18 g / cm ³ and a thickness of 1.5 mm, and a lower layer of the polyester nonwoven fabric having an average fiber diameter of 1.2 μm has a packing density of 0.2 g / cm ³ and thickness 3 mm, filled in a container having an effective filtration area of 67 mm × 67 mm, and then dissolving the above copolymer solution in special grade ethanol to a concentration of 0.01 g / dl It filled in the container and left still for 1 minute. Then, the copolymer liquid filled with nitrogen gas was expelled, and then nitrogen gas was added at 5 L / L for 10 minutes.
By continuing to flow for minutes, and further vacuum-drying at 70 ° C. for 7 hours, a leukocyte-removing filter material and a leukocyte-removing filter device composed of the material, in which a polyester nonwoven fabric was coated with the above copolymer, were prepared. 456 ml of whole blood prepared by adding 56 ml of CPD to 400 ml of blood
Prepared by removing 200 ml of platelet-rich plasma by centrifugation within 8 hours after blood collection and storing 320 ml of red blood cell concentrate (hematocrit 69%) stored at 4 ° C for 3 days.
After leaving it at room temperature (26 ° C.) until it reached 5 ° C., it was filtered by the above filter device. When the filtration was started, the filter device was connected to the blood bag containing the red blood cell preparation via the blood circuit, and then the blood bag was grasped by hand and pressurized to forcibly fill the blood in the filter device. Thus, after the blood is filled in the filter device, the drop is 1.0 m.
Blood was allowed to flow, and the blood was filtered until there was no blood in the blood bag, and the filtered blood was collected (hereinafter, the collected red blood cell preparation is referred to as a collected liquid).

The erythrocyte preparation before filtration (hereinafter referred to as pre-filtration liquid) and the volume of the recovered liquid and the number of white blood cells were measured to obtain the white blood cell residual rate. Leukocyte residual rate = (number of white blood cells in collected liquid) / (number of white blood cells in pre-filtration liquid) The volume of the pre-filtration liquid and the recovery liquid was obtained by dividing each weight by the specific gravity of blood (1.075). And The white blood cell concentration in the pre-filtration liquid was measured by the following method. Measurement of leukocyte concentration of pre-filtration solution: 10-fold diluted pre-filtration solution with Turk's solution was injected into a Burger Turk type hemocytometer, and white blood cells present in 4 large sections were counted using an optical microscope, This value was set to n ₁ . Pre-filtration liquid leukocyte concentration = n ₁ × (1/4) × 10 ⁵ cells / m
l White blood cell count in pre-filtration liquid = (pre-filtration liquid white blood cell concentration) x {pre-filtration liquid volume (ml)}

The white blood cell count of the collected liquid was measured by the method described below. Measurement of white blood cell count in the recovered solution: EBSS of 5% Ficoll 400DL in 100 ml of recovered solution
100 ml of the solution (hereinafter referred to as Ficoll solution) was added with shaking and mixing, and the mixture was allowed to stand for 40 minutes. After standing still, the supernatant was carefully collected so as not to disturb the sedimented erythrocyte layer, 100 ml of Ficoll solution was added again, and the same operation was repeated. The supernatant collected by the two operations was dispensed into a Corning 25350 centrifuge tube, and 840 x
After centrifugation for 15 minutes, the supernatant was discarded with an aspirator, taking care not to suck up the precipitate. Add 200 ml of hemolyzed blood (1.145% ammonium oxalate physiological saline) to each centrifuge tube and mix by shaking. Immediately 46
The supernatant was discarded with an aspirator, taking care not to suck up the precipitate by centrifugation at 8 xg for 10 minutes. The precipitate was collected in a centrifuge tube having a volume of 15 ml, hemolyzed blood was added to make the total volume 15 ml, and the mixture was allowed to stand at room temperature for 10 minutes. After standing still,
The supernatant was carefully discarded, leaving 0.5 ml containing the pellet, spun at 468 xg for 10 minutes. The solution containing the precipitate was sufficiently stirred to form a single cell suspension, and then a fluorescent staining solution (69.
50 mg of 9 mg / L acridine orange solution) was added and further stirred. This solution was injected into six modified Neubauer-type hemocytometers, and a large section 10 was obtained using an epi-illumination fluorescence microscope.
The white blood cells present in the 8 compartments were counted. The white blood cell count of the recovered liquid was calculated from the count value n ₂ by the following equation. White blood cell count = n ₂ × (1/108) × 10 ⁴ × 0.
55 x (1 / 0.55) x {collected liquid volume (ml)} / 1
00 The underlined portion is the white blood cell concentration (cells / ml) in a liquid (hereinafter referred to as a concentrated liquid) finally concentrated to 0.55 ml from 100 ml of the recovered liquid using Ficoll liquid, and the volume of the concentrated liquid is 0.55 ml. The white blood cell count is calculated by multiplying by. The reason for further dividing by 0.55 is that the recovery rate when leukocytes are recovered using Ficoll solution is 55%. As a result, the leukocyte residual rate was 10 ^−4.8 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.67, and the surface density of basic functional groups was 9.5 × 10 ⁻⁴ meq / m ² . The F value is 5.6 g for the fiber filter element having an average fiber diameter of 1.8 μm.
/ Sec / m, and the fiber filter element having an average fiber diameter of 1.2 μm was 3.3 g / sec / m. The pure water wetting time is
It was 16 seconds for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. The P value of the filter device was 13.8 mmAq / g.

[0043]

[Comparative Example 1] A polyester non-woven fabric having an average fiber diameter of 1.8 μm was packed at a density of 0.18 g / cm ³ and a thickness of 1.5 mm.
Then, the lower layer was filled with a polyester non-woven fabric having an average fiber diameter of 1.2 μm in a container having an effective filtration area of 67 mm × 67 mm so that the packing density was 0.2 g / cm ³ and the thickness was 3 mm. An experiment was conducted by flowing blood through the filter device thus prepared under the same conditions and method as in Example 1. As a result, the white blood cell residual rate was 10 ^-3.7 . Although the ratio of the basic functional group and the nonionic hydrophilic group on the surface of the non-woven fabric in this experiment was tried to be measured, both functional groups could not be detected. Further, the F value was 5.7 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm and 3.2 g / sec / m for the fiber filter element having an average fiber diameter of 1.2 μm. Further, when the deionized water wetting time of each non-woven fabric was measured, it was 1 minute or more for both non-woven fabrics having an average fiber diameter of 1.8 μm and 1.2 μm. Also, the P value of the filter device is
It was 14.7 mmAq / g.

[0044]

[Example 2] DM concentration added to special grade ethanol, HE
The experiment was conducted under the same conditions as in Example 1 except that the MA concentrations were 0.5 mol / L and 0.5 mol / L, respectively. As a result, the white blood cell residual rate was 10 ⁻⁵ . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.97, and the surface density of basic functional groups was 1.2 × 10 ⁻³ meq / m ² . Further, the F value is 5.5 g / for a fiber filter element having an average fiber diameter of 1.8 μm.
The fiber filter element having a second fiber diameter of 1.2 μm was 3.3 g / second / m. The deionized water wetting time was 19 seconds for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. Also, the P value of the filter device is
It was 14.2 mmAq / g.

[0045]

[Example 3] DM concentration in special grade ethanol, HE
The experiment was performed under the same conditions as in Example 1 except that the MA concentrations were 0.6 mol / L and 0.4 mol / L, respectively. As a result, the white blood cell residual rate was 10 ^-5.2 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 1.49, and the surface density of basic functional groups was 1.4 × 10 ⁻³ meq / m ² . Also, the F value is 5.4 g for a fiber filter element having an average fiber diameter of 1.8 μm.
/ Sec / m and the average fiber diameter of the fiber filter element of 1.2 μm was 3.0 g / sec / m. The pure water wetting time is
It was 20 seconds for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. The P value of the filter device was 15.1 mmAq / g.

[0046]

[Example 4] DM concentration added to special grade ethanol, HE
The experiment was conducted under the same conditions as in Example 1 except that the MA concentrations were 0.7 mol / L and 0.3 mol / L, respectively. As a result, the white blood cell residual rate was 10 ^-5.2 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 2.31, and the surface density of basic functional groups was 1.6 × 10 ⁻³ meq / m ² . Also, the F value is 5.4 g for a fiber filter element having an average fiber diameter of 1.8 μm.
/ Sec / m, and the fiber filter element having an average fiber diameter of 1.2 μm was 3.1 g / sec / m. The pure water wetting time is
It was 22 seconds for both the filter materials having the average fiber diameters of 1.8 μm and 1.2 μm. The P value of the filter device was 14.3 mmAq / g.

[0047]

[Example 5] DM concentration added to special grade ethanol, HE
The experiment was conducted under the same conditions as in Example 1 except that the MA concentrations were 0.8 mol / L and 0.2 mol / L, respectively. As a result, the white blood cell residual rate was 10 ^-5.0 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 3.98, and the surface density of basic functional groups was 1.8 × 10 ⁻³ meq / m ² . The F value is 5.6 g for a fiber filter element having an average fiber diameter of 1.8 μm.
/ Sec / m, and the fiber filter element having an average fiber diameter of 1.2 μm was 3.5 g / sec / m. The pure water wetting time is
It was 22 seconds for both the filter materials having the average fiber diameters of 1.8 μm and 1.2 μm. The P value of the filter device was 13.9 mmAq / g.

[0048]

[Comparative Example 2] Diethylaminoethyl methacrylate (hereinafter abbreviated as DE) was used instead of DM, and the DE concentration and HEMA concentration added to special grade ethanol were 0.2 and 0.2, respectively.
The experiment was conducted under the same conditions as in Example 1 except that the mol / L and 0.8 mol / L were used. As a result, the white blood cell residual rate is 1
It was ^0-3.8 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.2.
5. The surface density of basic functional groups is 4.7 × 10 ⁻⁴ meq /
It was m ² . Further, the F value was 5.3 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm and 3.3 g / sec / m for the fiber filter element having an average fiber diameter of 1.2 μm. In addition, the deionized water wetting time was an average fiber diameter of 1.8μ.
It was 11 seconds for both the filter material of m and 1.2 μm. Further, the P value of the filter device is 14.9 mmAq.
/ G.

[0049]

[Comparative Example 3] DM concentration added to special grade ethanol, HE
The experiment was conducted under the same conditions as in Example 1 except that the MA concentrations were 0.3 mol / L and 0.7 mol / L, respectively. As a result, the white blood cell residual rate was 10 ^−3.9 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.43, and the surface density of basic functional groups was 7.2 × 10 ⁻⁴ meq / m ² . The F value is 5.6 g for a fiber filter element having an average fiber diameter of 1.8 μm.
/ Sec / m, and the fiber filter element having an average fiber diameter of 1.2 μm was 3.6 g / sec / m. The pure water wetting time is
It was 13 seconds for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. The P value of the filter device was 15.3 mmAq / g.

[0050]

[Comparative Example 4] DM concentration added to special grade ethanol, HE
The experiment was conducted under the same conditions as in Example 1 except that the MA concentrations were 0.9 mol / L and 0.1 mol / L, respectively. As a result, the white blood cell residual rate was 10 ^−3.9 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 8.94, and the surface density of basic functional groups was 2.0 × 10 ⁻³ meq / m ² . The F value is 5.8 g for a fiber filter element having an average fiber diameter of 1.8 μm.
/ Sec / m and the average fiber diameter of the fiber filter element was 1.2 μm was 3.4 g / sec / m. The pure water wetting time is
The filter material having an average fiber diameter of 1.8 μm and 1.2 μm had a duration of 38 seconds. The P value of the filter device was 14.2 mmAq / g.

[0051]

Comparative Example 5 An experiment was conducted under the same conditions as in Example 1 except that DE was added to special grade ethanol at a concentration of 1 mol / L. As a result, the white blood cell residual rate was 10 ^-3.8 .
No nonionic hydrophilic group was detected on the surface of the filter material used in this experiment. The surface density of the basic functional group was 1.8 × 10 ⁻³ meq / m ² . The F value is 5.5 for the fiber filter element having an average fiber diameter of 1.8 μm.
The fiber filter element having a g / sec / m and an average fiber diameter of 1.2 μm was 3.4 g / sec / m. Further, the deionized water wetting time was 45 seconds for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. In addition, P of the filter device
The value was 14.7 mmAq / g.

[0052]

Comparative Example 6 When coating the copolymer used in Example 2, the copolymer concentration of the copolymer solution used was 0.
An experiment was conducted under the same conditions as in Example 2 except that the amount was 0003 g / dl. As a result, the white blood cell residual rate was 10 ^-3.8 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.97, and the surface density of basic functional groups was 3.5 × 10 ⁻⁵ meq / m ² . Further, the F value is 6.0 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm, and the average fiber diameter is 1.2 μm.
Of the fiber filter element was 3.5 g / sec / m. Also, the deionized water wetting time was 1.8 μm for the average fiber diameter and 1.2 μ for the average fiber diameter.
The filter material of m was 19 seconds. The P value of the filter device was 14.5 mmAq / g.

[0053]

Comparative Example 7 When coating the copolymer used in Example 2, the copolymer concentration of the copolymer solution used was 1 g.
The experiment was performed under the same conditions as in Example 2 except that the value was / dl. However, in this experiment, the flow rate of the red blood cell concentrate during filtration was markedly reduced, and of the 320 ml red blood cell concentrate used in the experiment, only 60 ml could be filtered, and therefore the white blood cells remained. The rate could not be measured. Further, remarkable hemolysis of erythrocytes was observed in the erythrocyte concentrate after this filtration treatment. The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.97, and the surface density of basic functional groups was 1.2 × 10 ^-1 meq / m ² . The F value is 2.5 g / sec / m for a fiber filter element having an average fiber diameter of 1.8 μm and the average fiber diameter is 1.2 μm.
m fiber filter element was 1.3 g / sec / m.
Further, the deionized water wetting time was as follows: average fiber diameter 1.8 μm, 1.2
It was 23 seconds with the filter material of μm. The P value of the filter device was 15.4 mmAq / g. Table 1 shows the results of Examples 1 to 5 and Comparative Examples 1 to 7 described above.
Are shown together.

[0054]

[Table 1]

[0055]

[Example 6] Dimethylaminoethyl acrylate (hereinafter abbreviated as DMA) 0.4 mol / g in special grade ethanol.
L and 2-hydroxyethyl acrylate (hereinafter abbreviated as HEA) were added so that the concentration was 0.6 mol / L, and the total amount was 250 ml. V-65 was added as a polymerization initiator to 0.
In order to obtain a concentration of 01 mol / L, under a nitrogen atmosphere,
After polymerizing at 45 ° C. for 4.5 hours, the substance precipitated by dropping in normal hexane was collected and freeze-dried to obtain a copolymer of DMA and HEA. Polyester nonwoven fabrics having an average fiber diameter of 32 μm, 19 μm, and 13 μm, which were produced by the spunbond method as a filter for removing gel and aggregates, had an average packing density of 0.28 g / cm ³ , and a thickness of 0.
The average packing density of the non-woven fabric having an average fiber diameter of 5.1 μm manufactured by the paneleron PF860 and the paper-making method is 0.2 so as to be 9 mm.
A container having an effective filtration cross-sectional area of 67 mm x 67 mm was sequentially filled toward 0 g / cm ³ and a thickness of 0.7 mm toward the downstream side of the container. A polyester non-woven fabric having an average fiber diameter of 1.8 μm was produced at a packing density of 0.18 g / cm ³ and a thickness of 1.5 mm. A polyester non-woven fabric was filled so that the packing density was 0.20 g / cm ³ and the thickness was 3.0 mm. The above copolymer was dissolved in a special grade ethanol solution at a concentration of 0.01 g / dl, and the copolymer liquid was charged into the above container and allowed to stand for 1 minute. Then, after expelling the copolymer liquid filled with nitrogen gas, further 1
Continue to flow nitrogen gas at 5 L / min for 0 minutes, and then at 70 ° C for 7 minutes.
By vacuum-drying for a period of time, a leukocyte-removing filter material in which the above-mentioned copolymer was coated on a polyester non-woven fabric and a leukocyte-removing filter device composed of the material were prepared. Whole blood (456 ml) prepared by adding 56 ml of CPD to 400 ml of blood was prepared by removing 200 ml of platelet-rich plasma by centrifugation within 8 hours after blood collection and stored at 4 ° C for 14 days. %) 320 ml at room temperature (26
After being left at (.degree. C.), it was filtered by the above filter device.
When the filtration was started, the filter device was connected to the blood bag containing the red blood cell preparation via the blood circuit, and then the blood bag was grasped by hand and pressurized to forcibly fill the blood in the filter device. Thus, after the filter device was filled with blood, blood was flowed at a drop of 1.0 m, and filtration was performed until the blood bag was free of blood. As a result, the white blood cell residual rate was 10 ^−4.3 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.66, and the surface density of basic functional groups was 1.1 × 1.
It was 0 ⁻³ meq / m ² . Further, the F value is 5.5 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm,
A fiber filter element having an average fiber diameter of 1.2 μm is also 3.3.
It was g / sec / m. The deionized water wetting time was within 1 second for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. The P value of the filter device is 14.
It was 3 mmAq / g.

[0056]

[Example 7] DMA concentration added to special grade ethanol, H
The experiment was conducted under the same conditions as in Example 6 except that the EA concentrations were 0.7 mol / L and 0.3 mol / L, respectively. As a result, the white blood cell residual rate was 10 ^−4.3 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 2.3, and the surface density of basic functional groups was 1.7 × 10 ⁻³ meq / m ² . The F value is 5.6 g / for a fiber filter element having an average fiber diameter of 1.8 μm.
The fiber filter element having a second fiber diameter of 1.2 μm was 3.3 g / second / m. The deionized water wetting time was 8 seconds for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. The P value of the filter device is 1
It was 4.7 mmAq / g.

[0057]

[Example 8] DMA concentration added to special grade ethanol, H
EA concentrations of 0.85 mol / L and 0.15 mol / L, respectively
An experiment was conducted under the same conditions and method as in Example 6 except that the L was set. As a result, the leukocyte residual rate was 10 ^−4.0 .
The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 5.7, and the surface density of basic functional groups was 2.0 × 10 ⁻³ meq / m ² . or,
The F value was 5.6 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm and 3.5 g / sec / m for the fiber filter element having an average fiber diameter of 1.2 μm. The deionized water wetting time was 15 seconds for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. The P value of the filter device was 15.0 mmAq / g.

[0058]

Comparative Example 8 An experiment was conducted under the same conditions and method as in Example 6, except that the polyester nonwoven fabric was used as it was as a filter material without coating the nonwoven fabric. As a result, the white blood cell residual rate was 10 ^−3.4 . Although the ratio of the basic functional group and the nonionic hydrophilic group on the surface of the non-woven fabric in this experiment was tried to be measured, both functional groups could not be detected. The F value was 5.6 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm and 3.6 g / sec / m for the fiber filter element having an average fiber diameter of 1.2 μm. Further, when the deionized water wetting time of each non-woven fabric was measured, it was 1 minute or more for both non-woven fabrics having an average fiber diameter of 1.8 μm and 1.2 μm. Also, the P value of the filter device is
It was 15.1 mmAq / g.

[0059]

[Comparative Example 9] DMA concentration added to special grade ethanol, H
An experiment was conducted under the same conditions and method as in Example 6, except that the EA concentrations were 0.3 mol / L and 0.7 mol / L, respectively. As a result, the white blood cell residual rate was 10 ^−3.6 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.43, and the surface density of basic functional groups was 8.0 × 10 ⁻⁴ meq / m ² . or,
The F value was 5.5 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm, and 3.7 g / sec / m for the fiber filter element having an average fiber diameter of 1.2 μm. The deionized water wetting time was within 1 second for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. The P value of the filter device was 13.9 mmAq / g.

[0060]

[Comparative Example 10] DMA concentration added to special grade ethanol,
HEA concentration is 0.9 mol / L, 0.1 mol / L, respectively
The experiment was conducted under the same conditions and method as in Example 6, except that As a result, the white blood cell residual rate was 10 ^−3.6 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 7.7, and the surface density of basic functional groups was 2.2 × 10 ⁻³ meq / m ² . Also, F
The values were 5.7 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm and 3.5 g / sec / m for the fiber filter element having an average fiber diameter of 1.2 μm. Further, the deionized water wetting time was 16 seconds for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. The P value of the filter device was 14.8 mmAq / g.

[0061]

Comparative Example 11 Under the same conditions as in Example 6, except that the copolymer solution used in coating the copolymer used in Example 6 had a copolymer concentration of 0.0003 g / dl. An experiment was conducted. As a result, the white blood cell residual rate is 10
It was ^-3.7 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.6.
6. The surface density of basic functional groups is 3.2 × 10 ⁻⁵ meq /
It was m ² . The F value was 5.4 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm and 3.4 g / sec / m for the fiber filter element having an average fiber diameter of 1.2 μm. In addition, the deionized water wetting time was an average fiber diameter of 1.8μ.
Both the m and 1.2 μm filter materials were within 1 second. The P value of the filter device is 13.8 mmAq.
/ G.

[0062]

Comparative Example 12 Under the same conditions as in Example 6, except that the copolymer solution used in coating the copolymer used in Example 6 had a copolymer concentration of 1.5 g / dl. An experiment was conducted. However, in this experiment, the flow rate of the red blood cell concentrate during the filtration was markedly reduced, and of the 320 ml red blood cell concentrate used in the experiment, only 30 ml could be filtered through the filter. The rate could not be measured. Further, remarkable hemolysis of erythrocytes was observed in the erythrocyte concentrate after this filtration treatment. The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.66, and the surface density of basic functional groups was 1.6 × 10 ⁻¹ m.
It was eq / m ² . Also, the F value is an average fiber diameter of 1.8μ.
m fiber filter element is 2.0 g / sec / m, average fiber diameter 1.2 μm fiber filter element is 1.0 g / sec / m
It was m. In addition, the deionized water wetting time was an average fiber diameter of 1.8.
It was within 1 second for both the filter material of μm and 1.2 μm. Also, the P value of the filter device is 16.8 mmA.
It was q / g. Examples 6 to 8 and Comparative Examples 8 to 1 described above
The results of No. 2 are summarized in Table 2.

[0063]

[Table 2]

[0064]

Example 9 An average fiber diameter of 32μ manufactured by the spunbond method as a filter for removing gel and aggregates.
m, 19 μm and 13 μm polyester non-woven fabrics were sequentially filled into a container having an effective filtration sectional area of 67 mm × 67 mm toward the downstream side of the container so that the average packing density was 0.27 g / cm ³ and the thickness was 1.8 mm. As a leukocyte-removing filter in the same container, on the downstream side, a polyester non-woven fabric having an average fiber diameter of 1.7 μm produced by a melt-blowing method was packed at a packing density of 0.21 g / cm ³ and a thickness of 0.6 mm. Similarly, a polyester non-woven fabric having an average fiber diameter of 1.2 μm produced by the melt-blowing method was packed at a packing density of 0.24 g / cm ³ and a thickness of 3.7 m.
When the copolymer used in Example 6 is coated with the copolymer solution, the copolymer concentration of the copolymer solution used is 0.1 g / dl, and the blood product is stored for 3 days. The experiment was conducted under the same conditions as in Example 6 except that As a result, the white blood cell residual rate was 10 ^−5.9 . In the filter material used in this experiment, the ratio of basic functional groups to nonionic hydrophilic groups was 0.66, and the surface density of basic functional groups was 1.1 × 10 ^-2 meq / m ² . The F value is 5.2 g / for a fiber filter element having an average fiber diameter of 1.7 μm.
The fiber filter element having an average fiber diameter of 1.2 μm was 2.8 g / sec / m. The deionized water wetting time was within 3 seconds for both filter materials having an average fiber diameter of 1.7 μm and 1.2 μm. The P value of the filter device was 16.8 mmAq / g.

[0065]

Example 10 An average fiber diameter of 32μ manufactured by a spunbond method as a filter for removing gel and aggregates.
m, 19 μm and 13 μm polyester non-woven fabrics were sequentially filled into a container having an effective filtration sectional area of 67 mm × 67 mm toward the downstream side of the container so that the average packing density was 0.26 g / cm ³ and the thickness was 1.9 mm. As a leukocyte-removing filter in the same container, on the downstream side, a polyester non-woven fabric having an average fiber diameter of 1.7 μm produced by the melt-blowing method was packed at a packing density of 0.2 g / cm ³ and a thickness of 0.6 mm, and further on the downstream side. Similarly, a polyester non-woven fabric having an average fiber diameter of 1.2 μm produced by the melt-blowing method was filled with a packing density of 0.25 g / cm ³ and a thickness of 3.6 mm.
The same as in Example 9 except that the copolymer concentration of the copolymer solution used in coating the copolymer used in Example 6 was 0.3 g / dl. The experiment was conducted under the conditions. As a result, the white blood cell residual rate was 10 ^-6.2.
Met. The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.66, and the surface density of basic functional groups was 3.2 × 10 ^-2 meq / m ² . The F value is 5.0 g / sec / m for the fiber filter element having an average fiber diameter of 1.7 μm and the average fiber diameter is 1.2 μm.
m fiber filter element was 2.6 g / sec / m.
Also, the deionized water wetting time was an average fiber diameter of 1.7 μm, 1.2.
It was 3 seconds for both μm filter materials. The P value of the filter device was 17.6 mmAq / g.

[0066]

Example 11: Average fiber diameter of 32μ manufactured by the spunbond method as a filter for removing gel and aggregates.
m, 19 μm and 13 μm polyester non-woven fabric were sequentially filled in a container having an effective filtration cross-sectional area of 67 mm × 67 mm toward the downstream side of the container so that the average packing density was 0.27 g / cm ³ and the thickness was 1.5 mm. As a leukocyte-removing filter in the same container on the downstream side, a polyester non-woven fabric having an average fiber diameter of 1.7 μm produced by a melt-blowing method was packed at a packing density of 0.22 g / cm ³ and a thickness of 0.6 mm, and further downstream thereof. Similarly, a polyester non-woven fabric having an average fiber diameter of 1.2 μm produced by the melt-blowing method was filled with a packing density of 0.28 g / cm ³ and a thickness of 4.0 m.
The same as Example 2 except that the copolymer concentration of the copolymer solution used in coating the copolymer used in Example 2 was 0.1 g / dl. The experiment was conducted under the condition of. As a result, the white blood cell residual rate is 10
It was ^-6.3 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.9.
7. The surface density of basic functional groups is 1.2 × 10 ^-2 meq /
It was m ² . The F value was 5.2 g / sec / m for the fiber filter element having an average fiber diameter of 1.7 μm and 2.5 g / sec / m for the fiber filter element having an average fiber diameter of 1.2 μm. Also, the deionized water wetting time was 1.7 μm for the average fiber diameter.
It was 25 seconds for both the m and 1.2 μm filter materials. The P value of the filter device is 23.4 mmAq.
/ G.

[0067]

Example 12 Average fiber diameter of 32μ manufactured by spunbond method as a filter for removing gel and aggregates
m, 19 μm and 13 μm polyester non-woven fabric were sequentially filled into a container having an effective filtration cross-sectional area of 67 mm × 67 mm toward the downstream side of the container so that the average packing density was 0.24 g / cm ³ and the thickness was 2.0 mm. As a leukocyte-removing filter in the same container, on the downstream side, a polyester non-woven fabric having an average fiber diameter of 1.7 μm produced by the melt-blowing method was packed at a packing density of 0.21 g / cm ³ and a thickness of 0.6 mm, and further downstream thereof. Similarly, a polyester non-woven fabric having an average fiber diameter of 1.2 μm produced by the melt-blowing method is packed with a packing density of 0.32 g / cm ³ and a thickness of 3.5 m.
The same as Example 11 except that the copolymer concentration of the copolymer solution used in coating the copolymer used in Example 2 was 0.3 g / dl. The experiment was conducted under the condition of. As a result, the white blood cell residual rate is 10
It was ^-6.7 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.9.
7. Surface density of basic functional groups is 3.5 × 10 ^-2 meq /
It was m ² . The F value was 5.0 g / sec / m for the fiber filter element having an average fiber diameter of 1.7 μm, and 2.4 g / sec / m for the fiber filter element having an average fiber diameter of 1.2 μm. Also, the deionized water wetting time was 1.7 μm for the average fiber diameter.
It was 28 seconds for both the m and 1.2 μm filter materials. The P value of the filter device is 25.8 mmAq.
/ G.

[0068]

[Example 13] Dimethylaminomethyl methacrylate (hereinafter abbreviated as DM) at 0.6 mol / L and glycerin monomethacrylate (hereinafter referred to as GMMA) in special grade ethanol
Abbreviated) was added to a concentration of 0.4 mol / L, and the total amount was 250 ml. V-65 was added as a polymerization initiator to a concentration of 0.05 mol / L, and the mixture was polymerized in a nitrogen atmosphere at 45 ° C. for 4.0 hours and then dropped into normal hexane to collect the precipitated substance. Freeze-dried and DM
To obtain a copolymer of GMMA. Average fiber diameter 1.8μ
m non-woven fabric with a packing density of 0.18 g / c
m ³ and a thickness of 1.5 mm, and an average fiber diameter of 1.
2 μm polyester non-woven fabric with a packing density of 0.2 g / cm
³ , effective filtration area 65mm × so that the thickness is 3mm
After being filled in a 65 mm container, a copolymer liquid prepared by dissolving the above copolymer in a special grade ethanol solution to a concentration of 0.01 g / dl was filled in the above container and allowed to stand for 1 minute.
Then, after expelling the copolymer liquid filled with nitrogen gas, nitrogen gas was continued to flow at 5 L / min for 10 minutes, and further vacuum dried at 70 ° C. for 7 hours to leukocytes coated with the above copolymer on a polyester nonwoven fabric. A removal filter material and a leukocyte removal filter device made of the material were prepared. 56 ml of C in 400 ml of blood
From 456 ml of whole blood prepared by adding PD, 200 ml of platelet-rich plasma was removed by centrifugation within 8 hours after blood collection, and 320 ml of red blood cell concentrate (hematocrit 69%) stored at 4 ° C. for 3 days was added to 25 ml. After being left at room temperature (26 ° C) until the temperature reached ℃, it was filtered by the above filter device. When the filtration was started, the filter device was connected to the blood bag containing the red blood cell preparation via the blood circuit, and then the blood bag was grasped by hand and pressurized to forcibly fill the blood in the filter device. Thus, after the filter device was filled with blood, blood was flowed at a drop of 1.0 m, and filtration was performed until the blood bag was free of blood. As a result, the white blood cell residual rate was 10 ^−4.5 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.75, and the surface density of basic functional groups was 1.1 × 10 ⁻³ meq / m ² . Further, the F value is 5.8 g / for a fiber filter element having an average fiber diameter of 1.8 μm.
The fiber filter element having an average fiber diameter of 1.2 μm was 2.0 g / sec / m. The deionized water wetting time was within 1 second for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. The P value of the filter device was 13.7 mmAq / g.

[0069]

Example 14 DM was added to special grade ethanol at a concentration of 0.6 mol / L and methoxytriethylene glycol methacrylate (hereinafter abbreviated as MTG) to a concentration of 0.4 mol / L, and the total amount was adjusted to 250 ml. did. V-65 was added as a polymerization initiator to a concentration of 0.05 mol / L, the mixture was polymerized at 45 ° C. under a nitrogen atmosphere for 4.0 hours, and then dropped into normal hexane to collect the precipitated substance. And freeze-dried to obtain a copolymer of DM and MTG. An experiment was conducted under the same method and conditions as in Example 13 except that this copolymer was used. As a result, the white blood cell residual rate was 10 ^−4.7 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 1.6, and the surface density of basic functional groups was 1.1 × 10 ⁻³ meq / m ² . . The F value was 5.7 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm and 2.3 g / sec / m for the fiber filter element having an average fiber diameter of 1.2 μm. In addition, the deionized water wetting time was an average fiber diameter of 1.8 μm and 1.2 μm.
It was 4 seconds for both filter materials. The P value of the filter device was 14.2 mmAq / g.

[0070]

Example 15 In a special grade ethanol, DM was adjusted to a concentration of 0.4 mol / L, MTG to a concentration of 0.4 mol / L, and methyl methacrylate (hereinafter abbreviated as MMA) to a concentration of 0.2 mol / L. In addition, the total amount was 250 ml. V-65 was added as a polymerization initiator to a concentration of 0.05 mol / L, the mixture was polymerized at 45 ° C. under a nitrogen atmosphere for 4.0 hours, and then dropped into normal hexane to collect the precipitated substance. And lyophilized to obtain a copolymer of DM, MTG and MMA.
The same method as in Example 13 except that this copolymer was used,
The experiment was conducted under the conditions. As a result, the white blood cell residual rate is 10
It was ^-4.8 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 1.2,
The surface density of the basic functional group is 7.6 × 10 ⁻⁴ meq / m ^2.
Met. The F value is 5.9 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm, and the average fiber diameter is 1.2.
The μm fiber filter element was 2.0 g / sec / m. Also, the deionized water wetting time was an average fiber diameter of 1.8 μm,
It was 18 seconds for both the 1.2 μm filter materials. The P value of the filter device was 14.0 mmAq / g.

[0071]

Example 16 DM was added to special grade ethanol at a concentration of 0.6 mol / L and octaethylene glycol methacrylate (hereinafter abbreviated as OEM) to a concentration of 0.4 mol / L, and the total amount was 250 ml. . V- as a polymerization initiator
65 was added so as to have a concentration of 0.05 mol / L, and the mixture was polymerized at 45 ° C. for 4.0 hours under a nitrogen atmosphere, then dropped into normal hexane and the precipitated substance was collected and freeze-dried. And an OEM copolymer were obtained. An experiment was conducted under the same method and conditions as in Example 13 except that this copolymer was used. As a result, the white blood cell residual rate was 10 ^−4.5 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.77, and the surface density of basic functional groups was 7.3 × 10 ⁻⁴ meq / m ² . or,
The F value was 5.7 g / sec / m for the fiber filter element having an average fiber diameter of 1.8 μm, and 2.6 g / sec / m for the fiber filter element having an average fiber diameter of 1.2 μm. The deionized water wetting time was within 1 second for both filter materials having an average fiber diameter of 1.8 μm and 1.2 μm. The P value of the filter device was 14.5 mmAq / g.

[0072]

Example 17 In a special grade ethanol, 0.4 mol / L of DMA and methoxyethylene glycol methacrylate having a repeating number of oxyethylene of 30 (hereinafter referred to as MPG) are used.
Abbreviated) was added to a concentration of 0.6 mol / L to make the total amount 250 ml. V-65 was added as a polymerization initiator to a concentration of 0.05 mol / L, polymerized at 45 ° C. for 2.5 hours in a nitrogen atmosphere, and then dropped into normal hexane to collect the precipitated substance. Freeze-dried and DM
A copolymer of A and MPG was obtained. Polyester nonwoven fabrics having an average fiber diameter of 32 μm, 19 μm and 13 μm produced by a spunbond method as a gel and agglomerate removing filter were filled with an average packing density of 0.28 g / cm ³ and a thickness of 0.
9 mm, and further using Paneron PF860 as a filter for removing fine agglomerates and polyester non-woven fabric having an average fiber diameter of 5.1 μm manufactured by the spunlace method so that the packing density is 0.20 g / cm ³ and the thickness is 0.7 mm. Then, a container having an effective filtration cross-sectional area of 67 mm × 67 mm was sequentially filled toward the downstream side of the container, and further, a polyester non-woven fabric having an average fiber diameter of 1.8 μm manufactured by the melt blow method was used as a leukocyte removal filter in the downstream side of the same container. packing density 0.18 g / cm ^3, so that the thickness of 1.5 mm, further the downstream side also average fiber diameter 1.2μm polyester nonwoven fabric produced by a melt blow method packing density 0.20 g / cm ^3, a thickness It was filled so as to be 3.0 mm. Next, the above copolymer was dissolved in a special grade ethanol solution to a concentration of 0.01 g / dl, filled in the above container, and allowed to stand for 1 minute. Then, after expelling the copolymer liquid filled with nitrogen gas, another 10
Nitrogen gas was kept flowing at 5 L / min for 1 minute, and further vacuum dried at 70 ° C. for 7 hours to prepare a leukocyte-removing filter material in which the above-mentioned copolymer was coated on a polyester non-woven fabric and a leukocyte-removing filter device comprising the material. Prepared by removing 200 ml of platelet-rich plasma by centrifugation from 456 ml of whole blood prepared by adding 56 ml of CPD to 400 ml of blood within 8 hours after blood collection,
Red blood cell concentrate (hematocrit 6) stored at 4 ° C for 12 days
5%) 320 ml at room temperature (26 ° C) until it reaches 25 ° C
After left to stand, it was filtered through the above filter. When the filtration was started, the filter device was connected to the blood bag containing the red blood cell preparation via the blood circuit, and then the blood bag was grasped by hand and pressurized to forcibly fill the blood in the filter device. Thus, after the blood was filled in the filter device, blood was flowed with a drop of 1.2 m, and filtration was carried out until the blood bag was free of blood. As a result, the leukocyte residual rate was 10 ^−4.0 . The ratio of basic functional groups to nonionic hydrophilic groups of the filter material used in this experiment was 0.7, and the surface density of basic functional groups was 1.5 × 10 ⁻⁴ me.
It was q / m ² . The F value is an average fiber diameter of 1.8 μm.
Fiber filter element of 5.5 g / sec / m, and fiber filter element having an average fiber diameter of 1.2 μm is 2.9 g / sec / m.
Met. In addition, the deionized water wetting time was an average fiber diameter of 1.8μ.
It was 9 seconds for both the m and 1.2 μm filter materials.
The P value of the filter device is 13.9 mmAq / g.
Met. The results of Examples 13 to 17 described above are summarized in Table 3.

[0073]

[Table 3]

Claims (1)

[Claims] 1. A surface has a basic functional group and a nonionic hydrophilic group, and the molar ratio of the basic functional group to the nonionic hydrophilic group on the surface is in the range of 0.6 to 6, and Whole blood or red blood cell preparation comprising a fiber or a polymer porous body having continuous pores, characterized in that basic functional groups are present on the surface at a density of 5 × 10 ^{−5 to} 0.1 meq / m ^2. Filter material for removing white blood cells from the.