JP2001129078A - White blood cell selectively removing method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a white blood cell selectively removing method to selectively and efficiently remove white blood cells from a whole blood preparation containing red blood cells, platelets, plasma components and white blood cells while suppressing the loss of the white blood cells, the platelets and the plasma components as much as possible. SOLUTION: For this white blood cell selectively removing method, a filter wherein an effective filtering area (cm2)/ a filter medium thickness (cm) is >=20 cm and <180 cm, and which allows red blood cells, plasma components and platelets to pass but removes white blood cells, is used. In this case, the filter filters whole blood at a filtration rate of >=15 mL/m2 and <50 mL/m2 per unit surface area of the filter medium filled in the filter.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for selectively removing leukocytes from a cell suspension such as blood. More specifically, the present invention relates to a leukocyte removal method for selectively and efficiently removing leukocytes from a whole blood product containing erythrocytes, platelets, plasma components and leukocytes while minimizing the loss of erythrocytes, platelets and plasma components. .

[0002]

2. Description of the Related Art With the recent advance in blood transfusion medicine, so-called component blood transfusion, which transfuses only components required by a blood recipient, is generally performed. Component transfusions include red blood cell transfusion, platelet transfusion, plasma ring blood, etc., depending on the type of blood component required by the recipient.The blood component products used for these transfusions include concentrated red blood cell products, concentrated platelet products , Plasma preparations and the like. In recent years, so-called leukocyte-removal transfusion, in which a blood product is transfused after removing leukocytes mixed in the blood product, has become widespread. This may include relatively minor side effects such as headache, nausea, chills, and non-hemolytic fever associated with blood transfusions, or severe allergens such as alloantigen sensitization, viral infection, and GVHD after blood transfusion that have a serious effect on the recipient. It has been clarified that such adverse side effects are mainly caused by leukocytes mixed in blood products used for blood transfusion.

[0003] As a method for removing leukocytes from blood products, there is a filter method for removing leukocytes using a filter material such as a fiber material or a porous material having continuous pores. The filter method is currently the most popular method because it has advantages such as excellent leukocyte removal ability, simple operation, and low cost. At present, a method of removing leukocytes by filtering a whole blood product or each blood component product with a leukocyte removal filter at a blood center or a bedside directly transfusing a blood recipient is used.

[0004] Currently, leukocytes are removed by a method of removing leukocytes by filtering each blood component prepared by centrifuging a whole blood product with a filter suitable for each blood component. A blood product is roughly classified into a method of filtering a blood product to remove leukocytes and then centrifuging to prepare a blood component product. The method of filtering with a filter after adjusting the blood component preparation by centrifugation requires a filter for each blood component preparation, and thus has a problem that it is costly and that it takes time to remove leukocytes.

[0005] On the other hand, a method of removing leukocytes by filtering a whole blood product with a filter, and then adjusting the blood component product is basically cost-effective because the leukocytes can be removed by one filter, and the operation is difficult. Is a preferred method because it can be simplified. However, a commercially available filter for whole blood products removes not only leukocytes but also highly adherent platelets at the same time, and thus it was substantially impossible to prepare a platelet product. As a method for solving such a problem, Japanese Patent Publication No. Hei 6-51060
JP-A-6-59304 discloses a non-woven fabric coated with a polymer having a trace amount of positive charge and a hydrophilic group as a filter material, and by using a filter filled with the filter material, a leukocyte is obtained from a whole blood preparation. A method for selectively removing blood components is disclosed.

However, as a result of faithful re-testing of these prior arts with whole blood products, the present inventors have found that when the platelet loss rate is low, the ability to remove leukocytes is insufficient. It is understood that there is a problem that the platelet loss rate is increased when the amount of the platelet is increased, and it is still possible to provide a selective leukocyte removal method that simultaneously satisfies both high leukocyte removal ability and low platelet loss from a whole blood product. Has not been reached.

[0007]

An object of the present invention is to reduce the loss of red blood cells, platelets and plasma components from whole blood products,
Another object of the present invention is to provide a method for removing leukocytes which removes leukocytes with high efficiency, and in particular, to provide a method for selectively removing leukocytes having an extremely excellent balance, which achieves both high leukocyte removal ability and low platelet loss at the same time.

[0008]

Means for Solving the Problems The present inventors have conducted intensive studies on a method for removing leukocytes which achieves the above object, and as a result,
Effective filtration area (cm ² ) / filter material thickness (cm) is 20 cm
Using a filter having a size of not less than 180 cm and 15 mL / m ² per unit surface area of the filter medium filled in the filter.
It has been found that the object of the present invention can be achieved by a method of filtering a whole blood product with a filtration amount of less than 50 mL / m ² . That is, although the mechanism is unknown, the ratio of the effective filtration area / thickness of the filter and the amount of whole blood to be filtered per surface area of the filter medium are extremely important for the balance between the platelet loss rate and the leukocyte removal ability. And completed the present invention.

Further, in the leukocyte removal method of the present invention, when processing whole blood, it is preferable that the average linear velocity is filtered in a low linear velocity region of 0.05 cm / min or more and less than 0.40 cm / min. Was found. It has been found that when the filtration is performed at a linear velocity in such a specific range, the balance between the leukocyte removal ability and the performance of platelet loss is more excellent. In general, since platelets have high adhesiveness, platelets tend to adhere to the filter medium in an extremely low linear velocity region, and as a result, the recovery rate tends to decrease. However, it was found that the loss of platelets was suppressed by filtering in an appropriate linear velocity region. The detailed mechanism by which platelet loss is suppressed in the appropriate linear velocity region is not well understood at this time, but this result was unexpected,
And it was surprising.

[0010] Furthermore, this result is more effective when a leukocyte removal filter in which the filter substrate is coated with a hydrophilic polymer is used. In particular, the hydrophilic polymer is composed of a nonionic hydrophilic group and a basic nitrogen-containing functional group. A remarkable effect is obtained when the polymer has

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Whole blood or a whole blood preparation as referred to in the present invention refers to a whole blood sample containing an anticoagulant such as ACD (acid citrate dextrose) or CPD (cytophosphate phosphate dextrose). It is a blood product within 3 days, preferably within 1 day. In particular, in order to keep the loss rate of platelets low, the whole blood product after blood collection is preferably stored at room temperature. Usually, a flexible polyvinyl chloride bag or the like is suitably used for storing such a whole blood product.

[0012] The effective filtration area of the filter referred to in the present invention means a direction perpendicular to the direction of blood flow, through which blood can flow.
The area of the filter (cm ² ), that is, the effective area of the filter perpendicular to the blood flow direction. Further, the filter medium thickness (cm) of the present invention refers to the thickness of the filter medium in the direction of blood flow in the effective filtration area, and is the thickness when the filter is actually filled. The measurement of the filter medium thickness, for example, after removing the filter medium from the filter,
The thickness is determined by compressing the filter with a suitable jig to the actual thickness of the filter. However, when the thickness of the filter medium in the filter is not uniform, five or more thicknesses are arbitrarily measured, and the average value is defined as the thickness of the filter medium. By dividing the effective filtration area of the filter thus measured by the thickness of the filter medium, the ratio of effective filtration area / filter medium thickness is determined. If this value is less than 20 cm, the time required for filtration of the whole blood product becomes too long, and if the whole blood product contains microaggregates, clogging tends to occur, which is not preferable. On the other hand, if this value exceeds 180 cm, the ability to remove leukocytes is undesirably reduced. More preferably, it is 55 cm or more and less than 160 cm, and still more preferably 75 cm or more and less than 140 cm.

The surface area of the filter medium is determined by measuring the specific surface area of the filter medium by a known BET method and multiplying by the weight of the filter medium at the effective filtration area of the filter. The filtration amount of whole blood per unit surface area of the filter medium referred to in the present invention is a value obtained by dividing the amount of filtered whole blood (including the anticoagulant) by the surface area of the filter medium filled in the filter. If the value is less than 15 mL / m ² , the loss rate of platelets increases, which is not preferable. If it exceeds 50 mL / m ² , the ability to remove leukocytes decreases, which is not preferable. More preferably, 20 mL / m2
It is at least 40 mL / m ² . The filtered amount (mL) of whole blood is obtained by measuring the weight (g) of whole blood filtered by a balance or the like and dividing the value by 1.05 (specific gravity of whole blood).

The average linear velocity of the present invention refers to an average flow velocity (mL / min = cm ³ / min) when whole blood is filtered by a filter.
It is the value divided by the effective filtration area of the filter. The average flow rate referred to here is, for example, the filtration time required for filtering a whole blood with a filter until the container or bag containing the whole blood to be filtered is substantially empty, during which time the filtration is performed. It is the value obtained by dividing the amount of whole blood obtained. When the average linear velocity obtained from the average flow velocity and the effective filtration area of the filter is less than 0.05 cm / min, the loss rate of platelets increases, the time required for filtration increases, It is not preferable because the amount of blood lost in the filter may increase due to an increase in size due to an increase in cross-sectional area.
If the average linear velocity exceeds 0.40 cm / min, the reason is not clear, but it is not preferable because the platelet loss rate may increase and the leukocyte removal ability may decrease. More preferably, it is not less than 0.2 cm / min and less than 0.35 cm / min.

The filter medium of the present invention refers to a porous element having an average pore size of 2 μm or more and less than 20 μm. The average pore size refers to a value obtained by measurement by a bubble point method. For example, using a Coulter R porometer manufactured by Coulter Electronics Co., Ltd., the average pore size (mean flow pore size: MFP) is determined using about 50 mg of a sample. Can be measured. If the average pore size is less than 2 μm, it is not preferable because the whole blood product becomes difficult to flow, and if it is more than 20 μm, the leukocyte removing ability tends to decrease, which is not preferable. A more preferable range of the average pore diameter is 3 μm or more and less than 15 μm, and still more preferably 5 μm or more and less than 12 μm.

Examples of the porous element that can be used as the filter medium of the present invention include a fibrous material represented by a nonwoven fabric, a woven fabric, and a net cloth, a porous film having continuous pores, a sponge-like structure, and the like. Among these, nonwoven fabric fibers are preferably used as the filter material from the viewpoint of high leukocyte removal ability per unit weight and easy production. When fibers are used as the filter medium, the average fiber diameter is 0.3 μm or more and 3.0 μm.
Is preferably less than 0.5 μm and 1.8 or less.
It is preferably less than μm. 0.3μ average fiber diameter
If it is less than m, the pressure loss at the time of filtering the whole blood product may be too high to be practical, and if it is more than 3.0 μm, the leukocyte removal ability may decrease, which is not preferable. The measurement of the average fiber diameter mentioned here is performed by the following procedure. A portion of the filter medium itself consisting of fibers, which is regarded as substantially uniform, is sampled and photographed using a scanning electron microscope or the like. The width of the fiber in the direction perpendicular to the fiber axis is 50 points or more, preferably 100 points. The value obtained by dividing the total value of the individual fiber diameters measured and obtained by the number of measurements is defined as the average fiber diameter.

As the filter medium of the present invention, any material may be used as long as it does not easily damage blood or blood cell components.
Examples thereof include polyester, polyolefin, polyamide, polystyrene, polyacrylonitrile, cellulose, and cellulose acetate.

Further, the filter medium of the present invention comprises a so-called antithrombotic material, which has little effect on platelets and low platelet adhesion, and various known polymer materials which are widely used as hydrophilic materials. It is preferable to have it on the surface. In particular, a polymer material having a nonionic hydrophilic group and a positively charged basic nitrogen-containing functional group is preferable because of low platelet adhesion. here,
Examples of the nonionic hydrophilic group include a hydroxyl group, an ethylene oxide chain, and an amide group. Examples of the basic nitrogen-containing functional group include a primary amino group, a secondary amino group, a tertiary amino group, and a quaternary amino group. Examples include an ammonium group, and a nitrogen-containing aromatic group such as a pyridyl group and an imidazole group. Also,
The content of the basic nitrogen atom in the basic nitrogen-containing functional group is 0.0
It is desirably 5% by weight or more and less than 4.0% by weight, preferably 0.25% by weight or more and less than 1.5% by weight. If the content of the basic nitrogen atom is less than 0.05% by weight, it is not preferable because the white blood cells tend not to adhere together with the platelets, and if it exceeds 4.0% by weight, the platelets tend to easily adhere. Therefore, it is not preferable.

As a method for introducing the above-mentioned preferred polymer material to the surface of the filter medium, a graft method such as radiation grafting or plasma grafting, or a coating method using a polymer material can be mentioned. Among them, it is preferable to coat by a coating method because the operation is simple, the productivity is excellent, and a uniform coating layer is easily formed.
Polymer materials that can be used for the coating method include:
It can be synthesized from a monomer having a polymerizable functional group such as a vinyl group by ordinary radical polymerization, anionic polymerization or the like. In addition, two or more different kinds of different monomers can be synthesized by random copolymerization and block copolymerization. Chemical species capable of synthesizing a polymer material for coating include, for example, hydroxyethyl (meth) acrylate, methoxypolyethylene glycol (meth) acrylate, and (meth) acrylamide having a nonionic hydrophilic group. Examples thereof include (meth) acrylic acid derivatives such as dialkylaminoethyl (meth) acrylate having a functional group.

It is desirable that the coverage of the filter medium surface with a suitable polymer material is 50% or more, preferably 70% or more, and most preferably 90% or more. The coverage here means the ratio of the surface of the filter medium covered with the polymer material. If the coverage is less than 50%, a large number of platelet adsorption sites exist, and the platelet loss rate tends to increase, which is not preferable.

The coverage was measured by XPS (X-ray Photoe).
(Electron Spectroscopy) or the like. For example, the following method is used to coat a filter medium made of polyethylene terephthalate with a polymer of a (meth) acrylic acid derivative and measure the coverage by XPS. The XPS spectra of the filter material before and after coating, which is cut into a square of about 1 cm, and the polymer formed into a film are measured. Binding Energy obtained
Intensity au (angstrom uni)
From the spectrum of t)), the intensity of the CO component peak obtained by separating the peak of the C (carbon) 1s spectrum is set to 1, and the carboxylic acid component peak (appearing around 286 eV) relative to this CO component peak (appearing around 286 eV) (Appears near 289 eV)
The intensity ratio (F) is determined. The obtained F value is substituted into the following equation to calculate the coverage. The polymer material formed into a film is prepared by defoaming a polymer solution consisting of a polymer material and a solvent, casting it on a flat glass plate, etc., and evaporating and removing the solvent at a slow rate. I do. The coated filter medium and the polymer material formed into a film used in the measurement have a residual solvent amount of 1 ppm or less and a thickness of 0.1 mm or more.

Coverage (%) = ｛| Fa−Fb | / | Fp
−Fb |｝ × 100 (where, Fa: measured value of the filter material after coating with the polymer material, Fb: measured value of the filter material before coating with the polymer material, Fp: measured value of the polymer material formed into a film)

The filter preferably used in the present invention and
Is 0.1 g / cm^Three0.3g / c or more
m^ThreeLess than 0.17 g / cm^Three0.25g or more
/ Cm ^ThreeFill the filter with a packing density of less than
The leukocytes inside are removed but other blood components, namely red blood
Spheres, platelets, and plasma are filters that let through. here
The packing density referred to above is when the filter media is filled into the filter
The filter media weight for the effective filtration area
This is the value obtained by dividing by (effective filtration area × filter medium thickness) of the filter.
The packing density is 0.1 g / cm^ThreeLess than leukocyte removal
0.3g / cm^ThreeExceeds
It is not preferable because blood flow may be extremely reduced.
No.

Further, the filter of the present invention may be provided on the upstream and / or downstream side of the above-mentioned filter medium with microaggregates which are substantially ineffective for removing blood cells but may be contained in a whole blood product. A filter medium having a larger pore diameter may be filled in order to remove the water. Further, for the purpose of preventing deformation of the filter medium during blood filtration, another filter medium having higher strength may be filled.

In the leukocyte removal method of the present invention, the following filters (A) to (F) are particularly preferred. (A) A filter filled with a filter medium having an average pore size of 2 μm or more and less than 20 μm. (B) The filter according to (A), wherein the filter medium is a nonwoven fabric having an average fiber diameter of 0.3 μm or more and less than 3.0 μm. (C) The filter according to (A), wherein at least the surface of the filter medium is coated with a polymer material having a nonionic hydrophilic group and a basic nitrogen-containing functional group, and the coverage is 50% or more. (D) The filter according to (A), further comprising 0.05% by weight or more and less than 4.0% by weight of a basic nitrogen atom. (E) The packing density of the filter medium is 0.1 g / cm ³ or more and 0.3 g.
/ Cm ³ , the filter according to the above (A). (F) The filter according to the above (A), wherein the upstream and / or downstream sides of the filter medium are filled with another filter medium.

According to the method for selectively removing leukocytes of the present invention using such a filter, since a suitable linear velocity is set,
The filtration may be performed at a pressure difference of 0 cm or more and less than 200 cm, or at a constant flow rate using a pump or the like. After obtaining a whole blood product from which only white blood cells have been selectively removed in this way, the three components of red blood cell product, platelet product, and plasma product from which white blood cells have been removed can be prepared by a known centrifugation method. The method of the present invention uses one filter,
This is an extremely useful method because only white blood cells can be removed by a simple operation.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the scope of the present invention is not limited only to these Examples.

(Example 1) Four non-woven fabrics made of polyethylene terephthalate having an average fiber diameter of 1.2 μm were punched and laminated to a diameter of 30 mm, and immersed in a polymer solution having a concentration of 5 g / dl at 40 ° C. for 1 minute. Thereafter, a non-woven fabric after polymer coating was filled in a holder having a diameter of 30 mm, dry nitrogen was passed through for 4.5 minutes, and further vacuum drying was performed at 60 ° C. for 16 hours to produce a filter. The average pore size of the filter medium filled in the filter was 8 μm. The effective filtration area of the prepared filter was 4.9 cm ² , the thickness obtained by compressing the filter with a vice to the thickness when the filter was filled into the filter was 0.08 cm, the effective filtration area / filter thickness was 61 cm, and the effective filtration area was 61 cm. The weight of the filter media in the filtration area is 0.08
g, the packing density of the filter medium was 0.2 g / cm ³ , the specific surface area determined by the BET method was 2.4 m ² / g, and the polymer coverage was 92%.

The polymer used was a copolymer consisting of 2-hydroxyethyl methacrylate (hereinafter abbreviated as HEMA) and dimethylaminoethyl methacrylate (hereinafter abbreviated as DM), and was synthesized by ordinary radical polymerization. The polymerization conditions were such that the monomer concentration in ethanol was 1 mol / L, and azobisisobutyronitrile (AIBN) was used as an initiator at 1/200 mol / L to carry out a polymerization reaction at 60 ° C. for 8 hours. The obtained polymer contained about 3 mol% of DM (the content of the basic nitrogen atom was 0.1%).
3% by weight).

Using CPD as an anticoagulant, a whole blood preparation (6 mL) stored at room temperature for one day after blood collection was filtered through the above filter at a constant flow rate of 1.5 mL / min. The filtration rate per unit surface area of the filter medium was 31 mL / m ² , and the average linear velocity was 0.3 cm / min.

The measurement of leukocyte removal ability was performed by the following method. The leukocyte concentration in the whole blood product before filtration was measured using a light microscope after staining the leukocytes with the Turku solution. The leukocyte concentration in the whole blood product after filtration was determined by staining the leaked leukocytes with acridine orange solution and using a fluorescence microscope. From the leukocyte concentrations before and after filtration thus obtained, the leukocyte removal ability was determined by the following equation. Leukocyte removal ability = -Log (white blood cell concentration after filtration / white blood cell concentration before filtration)

The platelet loss rate and the erythrocyte recovery rate were determined by the following equations by measuring the platelet concentration and the erythrocyte concentration before and after filtration using a multi-item automatic blood cell counter (K-4500, manufactured by Sysmex). . Platelet loss rate = (1-platelet concentration after filtration / platelet concentration before filtration) × 100 (%) Red blood cell recovery rate = red blood cell concentration after filtration / red blood cell concentration before filtration ×
100 (%) The plasma total protein concentration before and after filtration was measured by the Burette method, and the recovery was calculated.

The leukocyte removal ability is 2.3 and the platelet loss rate is 1
3%. The value obtained by dividing the leukocyte removal ability by the platelet loss rate, which is an index of the balance between the leukocyte removal ability and the platelet loss rate of the filter, was 0.18 (-Log /%).
Red blood cell and plasma protein recovery was 100%.

Example 2 A whole blood product was filtered by the same operation as in Example 1 using a filter produced in the same manner as in Example 1 except that the number of nonwoven fabrics to be filled in the filter was changed to 6. did. The ratio of the effective filtration area of the filter / the thickness of the filter medium is 41, and the filtration amount per unit surface area of the filter medium is 21 m.
L / m ² . As a result, the leukocyte removal ability was 2.
8. The platelet loss rate was 18%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was 0.16 (-Log /%).

(Comparative Example 1) A whole blood product was filtered in the same manner as in Example 1 using a filter prepared in the same manner as in Example 1 except that the filtration amount of the whole blood product was changed to 2 mL.
The ratio of the effective filtration area of the filter / the thickness of the filter medium was 61, and the filtration amount per unit surface area of the filter medium was 11 mL / m ² . As a result, the leukocyte removal ability was 2.7, the platelet loss rate was 56%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was 0.05 (-Log /%).

(Comparative Example 2) A whole blood product was filtered by the same operation as in Example 1 using a filter prepared in the same manner as in Example 1 except that the number of nonwoven fabrics to be filled in the filter was two. did. The ratio of the effective filtration area of the filter / the thickness of the filter medium is 123, and the filtration amount per unit surface area of the filter medium is 64.
mL / m ² . As a result, the leukocyte removal ability was 0.1%.
9. The platelet loss rate was 11%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was 0.08 (-Log /%).

(Comparative Example 3) The effective filtration area is 3.1 cm 2
, A filter was prepared in which the same filter material as in Example 1 was filled in nine containers. Using this filter, whole blood product 8mL
Was filtered at a constant flow rate of 1.0 mL / min. The ratio of the effective filtration area of the filter / the thickness of the filter medium is 17, the filtration amount per unit surface area of the filter medium is 30 mL / m ² , and the average linear velocity is 0.32.
cm / min. As a result, the leukocyte removal ability was 3.
4. The platelet loss rate was 68%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was 0.05 (-Log /%).

(Comparative Example 4) The effective filtration area is 9.0 cm ²
, A filter was prepared by filling two containers with the same filter medium as in Example 1. Using this filter, whole blood product 6mL
Was filtered at a constant flow rate of 2.7 mL / min. The ratio of the effective filtration area / filter medium thickness of the filter is 225, the filtration amount per unit surface area of the filter medium is 35 mL / m ² , and the average linear velocity is 0.3.
It was 0 cm / min. As a result, the leukocyte removal ability was 1.
4. The platelet loss rate was 17%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was 0.08 (-Log /%).

Example 3 Effective filtration area is 9.0 cm ²
, A filter was prepared by filling five containers with the same filter medium as in Example 1. Using this filter, whole blood product 14m
L was filtered at a constant flow rate of 2.7 mL / min. The ratio of the effective filtration area of the filter / the thickness of the filter medium is 90, the filtration amount per unit surface area of the filter medium is 32 mL / m ² , and the average linear velocity is 0.3.
It was 0 cm / min. As a result, the leukocyte removal ability was 2.
7. The platelet loss rate was 11%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was about 0.25 (-Log /%).

Example 4 A filter was used in the same manner as in Example 1 except that the flow rate for filtering whole blood was 1.9 mL / min. The ratio of the effective filtration area of the filter / the thickness of the filter medium was 61, the amount of filtration per unit surface area of the filter medium was 31 mL / m ² , and the average linear velocity was 0.39 cm / min. As a result, the leukocyte removal ability was 2.1 and the platelet loss rate was 14%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was 0.15 (-Log /%).
Met.

Example 5 Filtration was performed in the same manner as in Example 1, except that the flow rate at the time of filtering whole blood was 0.3 mL / min. The ratio of the effective filtration area of the filter / the thickness of the filter medium was 61, the amount of filtration per unit surface area of the filter medium was 31 mL / m ² , and the average linear velocity was 0.06 cm / min. As a result, the leukocyte removal ability was 2.3 and the platelet loss rate was 17%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was 0.14 (-Log /%).
Met.

Example 6 Filtration was carried out using the same filter as in Example 1 except that the flow rate for filtering whole blood was 2.7 mL / min. The ratio of the effective filtration area of the filter / the thickness of the filter medium was 61, the filtration rate per unit surface area of the filter medium was 31 mL / m ² , and the average linear velocity was 0.55 cm / min. As a result, the leukocyte removal ability was 2.1 and the platelet loss rate was 16%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was 0.13 (-Log /%).
Met.

(Example 7) Filtration was carried out using the same filter as in Example 1 except that the flow rate at the time of filtering whole blood was 0.2 mL / min. The ratio of the effective filtration area of the filter / the thickness of the filter medium was 61, the filtration amount per unit surface area of the filter medium was 31 mL / m ² , and the average linear velocity was 0.04 cm / min. As a result, the leukocyte removal ability was 2.4 and the platelet loss rate was 20%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was 0.12 (-Log /%).
Met.

Table 1 shows the results of Examples 1 to 7 and Comparative Examples 1 to 4.

[Table 1]

From the above results, the effective filtration area of the present invention /
It can be seen that all of the leukocyte removal methods of Examples 1 to 7 which satisfy the requirements for the ratio of the filter material thickness and the amount of filtration per unit surface area are excellent in both the leukocyte removal ability and the platelet loss rate. In particular, in the filters of Examples 1 to 5 in which the linear velocity was also 0.05 to 0.4 cm / min, the value obtained by dividing the leukocyte removal ability by the platelet loss rate was about twice or more of the comparative example, It can be understood that the balance between the platelet loss rate and the platelet loss rate is extremely excellent.

The following Example 8 is an example in which the polymer material for coating the filter substrate is different from Examples 1 to 7, and Example 9 is an example in which the filter substrate is different from Examples 1 to 7. is there. (Example 8) Instead of the polymer used in Example 1, H
EMA and diethylaminoethyl methacrylate (hereinafter D
A filtration operation was performed in the same manner as in Example 1 except that a polymer (abbreviated as E) (the content of DE in the polymer was about 5 mol%) was coated. The polymer coverage was 90%, the ratio of the effective filtration area of the filter / the thickness of the filter medium was 61 cm, the filtration amount per unit surface area of the filter medium was 31 mL / m ² , and the average linear velocity was 0.31 cm / min. As a result, the leukocyte removal ability was 2.2 and the platelet loss rate was 15%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was 0.15 (-Log /%).
Met.

Example 9 The same filtration operation as in Example 1 was carried out except that the nonwoven fabric made of poly (trimethylene) terephthalate having an average fiber diameter of 1.4 μm was used instead of the nonwoven fabric made of polyethylene terephthalate used in Example 1. Was done. The average pore size of the filter medium filled in the filter is 10 μm,
The thickness of the filter medium is 0.08 cm, the ratio of the effective filtration area of the filter / the thickness of the filter medium is 61 cm, and the specific surface area of the filter medium is 2.0 m.
² / g, the filtration rate per unit surface area of the filter medium is 38 mL /
m ² , the average linear velocity was 0.31 cm / min, and the polymer coverage was 87%. As a result, the leukocyte removal ability was 1.
5. The platelet loss rate was 9%, and the value obtained by dividing the leukocyte removal ability by the platelet loss rate was 0.17 (-Log /%). From the above Examples 8 and 9, even when the coating material and the filter substrate are different, when the filter has the characteristics of the present invention, it is possible to perform the selective leukocyte removal satisfying both the leukocyte removal ability and the platelet loss rate. I understand.

[0047]

According to the method for selectively removing leukocytes of the present invention,
The balance between the ability to remove leukocytes from a whole blood product and the rate of platelet loss can be extremely improved. The white blood cell selective removal method of the present invention is to remove white blood cells selectively and efficiently from red blood cells, platelets, plasma components and whole blood products containing white blood cells while minimizing loss of red blood cells, platelets and plasma components. Was completed.

Claims (4)

[Claims] Claims 1. A filter using a filter to convert red blood cells from whole blood,
In the selective leukocyte removal method for removing leukocytes by passing plasma and platelets, the effective filtration area (cm ² ) / filter material thickness (cm) of the leukocyte selective removal filter is 20 cm or more and less than 180 cm, and the filter material filled in the filter is used. per unit surface area of 15 mL / m ² or more 50 mL / m ²
A method for selectively removing leukocytes, characterized by filtering whole blood with a filtration amount of less than. 2. The average linear velocity when filtering whole blood is 0.05.
2. The method for selectively removing leukocytes according to claim 1, which is at least cm / min and less than 0.4 cm / min. 3. The method for selectively removing leukocytes according to claim 1, wherein the filter is a filter for selectively removing leukocytes obtained by coating a filter medium with a hydrophilic polymer. 4. The hydrophilic polymer according to claim 1, wherein the hydrophilic polymer is a polymer having a nonionic hydrophilic group and a basic nitrogen-containing functional group.
4. The method for selectively removing leukocytes according to any one of 3.