JP2001347116A - White blood cell removing filter device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a white blood cell removing filter device and method which are capable of efficiently exhibiting the white blood cell removing ability of filter materials as the entire part of the filter materials is effectively utilized for removing the white blood cell when the white blood cells are removed from blood containing the white blood cells. SOLUTION: This white blood cell removing filter device is characterized in that the packing density of the white blood cell removing filter materials in a region inclusive of a region right under a blood introducing port of the white blood cell removing filter formed by packing the white blood cell removing filter material into a container having the blood introducing port in an upper part and a blood leading-out port in a lower part is higher than the packing density of the filter materials in the remaining regions. The method for removing the white blood cells from a white blood cell-containing liquid consists in injecting the white blood cell-containing liquid from the blood introducing port into the container and recovering the liquid filtered with the device from the blood leading-out port by using the white blood cell removing filter device.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a leukocyte removal filter device for removing leukocytes from a leukocyte-containing liquid such as a whole blood product, a concentrated red blood cell product or a concentrated platelet product, and a leukocyte removal filter device using the leukocyte removal filter device. It relates to the removal method.

[0002]

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

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

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

At present, methods for removing leukocytes from blood products are roughly classified into a centrifugal separation method for separating and removing leukocytes using a specific gravity difference of blood components using a centrifuge, and a fiber material such as a nonwoven fabric or the like. And a filter method for removing leukocytes using a filter material made of a porous material having continuous pores. The filter method for removing leukocytes by adhesion or adsorption is currently most popular because it has advantages such as easy operation and low cost.

The mechanism of leukocyte removal by a filter material such as a fiber material or a porous material is mainly based on the fact that leukocytes in contact with the filter material surface are adhered or adsorbed to the filter material surface. Therefore, as a means of improving the leukocyte removal ability in the conventional filter material,
Studies have been made on increasing the frequency of collision between the filter material and leukocytes, that is, reducing the fiber diameter and the pore size of the filter material, and increasing the packing density of the filter material in the filter device. No. 6,009,036. However, in a preparation containing a high proportion of red blood cells in the preparation, such as a whole blood preparation or a concentrated erythrocyte preparation, there is a limit to achieving high performance using only the above means. More specifically, as the frequency of contact of white blood cells with the filter material increases, the frequency and contact resistance of red blood cells present at high concentrations in the formulation with the filter material also increases, prolonging the processing time and destroying the red blood cell membrane. There is a problem that hemolysis is caused by this. For such a problem, the surface has a hydrophilic basic group containing a nonionic hydrophilic portion and a basic portion, and in the hydrophilic basic group, the hydrophilic portion is more than the basic portion. By using the leukocyte-removing filter material located on the terminal side, it is possible to achieve the leukocyte-removing ability having an extremely high affinity for leukocytes while suppressing the adhesion of erythrocytes.
4.

On the other hand, there has been studied a leukocyte removal filter material for the purpose of maintaining the leukocyte removal ability while improving the passage rate of platelets known as highly adherent cells.
Japanese Patent Application Laid-Open No. 1-249063 discloses a filter material having a hydrophilic and negatively charged surface.
No. 5812 discloses a filter material having a nonionic hydrophilic group and a basic nitrogen-containing functional group, and containing a basic nitrogen-containing functional group in an amount of 0.2% by weight or more and less than 4.0% by weight. Also,
EP0500472 aims to increase the platelet removal rate while maintaining good red blood cell permeability and leukocyte removal rate by using a filter material having a positive zeta potential when removing white blood cells and platelets from a red blood cell preparation. The disclosed technology is disclosed.

Further, the average fiber diameter is from 0.01 μm to 1.
WO97 / 2 is a filter material having a leukocyte-removing ability, which is obtained by introducing a network-like structure formed of 0 μm ultrafine fibers into a porous element having an average pore size of 1.0 μm to 100 μm.
3266. In addition, fiber diameter 0.01μm
A leukocyte removal manufactured by dispersing a fiber mass in which a number of the following small fiber pieces are aggregated and a short fiber having a length of 0.05 mm to 0.75 d and a fiber length of 3 mm to 15 mm in a dispersion medium, and then forming a dispersion liquid. An excellent leukocyte removal filter material is disclosed in Japanese Patent Application Laid-Open No. Hei 7-500990 and Japanese Patent Laid-Open No.
No. 77 discloses this. As described above, the leukocyte-removing ability per unit volume of the leukocyte-removing filter material has been remarkably improved by various measures.

However, in recent years, great demands have been raised in the market for leukocyte removal filters. One of the requirements is to improve the recovery rate of useful components, rather than improving leukocyte removal ability, and to perform an operation to recover useful components remaining in the filter and circuit using physiological saline or air. Make it unnecessary
The task is to save labor. In particular, regarding the improvement of the recovery rate of useful components, blood, which is a raw material of blood products, is often valuable blood provided by blood donation in good faith, and blood that remains in the leukocyte removal filter and cannot be recovered. Has the problem that it is wasted as it is with the filter and is wasted. Therefore, it is extremely significant to improve the recovery rate of useful components as compared with the existing leukocyte removal filter.

Therefore, in order to satisfy the above-mentioned market demand, a leukocyte-removing filter device which uses a leukocyte-removing filter material having a high leukocyte-removing ability per unit volume and is filled with a smaller amount of filter material than before has been used. It is considered to be. By using such a device, the amount of blood remaining in the filter decreases as the filling amount of the filter material is reduced, without performing the operation of recovering useful components remaining in the filter. It is thought that the recovery rate of the useful component is higher than that of the apparatus. In the market, there is another demand for a leukocyte removal filter, such as a desire to process a desired amount of blood in a short time. Therefore, the shape of the leukocyte removal filter device is considered to be a leukocyte removal filter device having a shape equal to or larger than the cross-sectional area of the conventional device and a thin filter material.

As described above, when the thickness of the filter material is reduced along with the reduction of the filter material, blood does not spread uniformly throughout the filter material. The part with few is easily generated. That is, since blood containing the number of leukocytes in excess of the leukocyte capturing capacity of the filter material flows in a portion where the amount of passed blood is large, there is a high possibility that a large amount of leukocytes that could not be captured will be mixed into the filtered blood. In addition, in a portion where the amount of blood passing is small, blood containing a leukocyte count equal to or less than the leukocyte trapping capacity of the filter material flows, so that it is possible to remove leukocytes with a margin and reduce the number of leukocytes mixed into the filtered blood. . In other words, in the case of a thin leukocyte removal filter device, a portion with a large amount of blood passage and a portion with a small amount of blood passage easily occur in the same filter device, so that the entire filter material is efficiently used for leukocyte removal. In some cases, it was difficult to efficiently exert the leukocyte removal ability of the filter material. If the density of the leukocyte-removing filter material filled in the leukocyte-removing filter device is the same in any part, blood tends to flow through a portion near the inlet.

[0012]

SUMMARY OF THE INVENTION The present invention relates to a method for removing leukocytes from blood containing leukocytes by using a thin leukocyte removal filter device. The problem with the prior art is that the entire filter material is not utilized for leukocyte removal, and it is difficult to efficiently exert the leukocyte removal capability of the filter material because the portion through which the amount of blood passage is small tends to occur. Is to solve.

[0013]

Means for Solving the Problems As a result of diligent studies on a leukocyte removal filter device for solving the above-mentioned problems, the present inventors have found that a container having a blood inlet at the upper part and a blood outlet at the lower part is provided in a container.
In the leukocyte removal filter filled with leukocyte removal filter material, by increasing the packing density of the leukocyte removal filter material in the area including immediately below the blood inlet, higher than the packing density of the filter material in the remaining area.
We found that we could solve the problem. Further, the present inventor uses the above-described leukocyte removal filter device, injects a leukocyte-containing liquid from a blood inlet, and collects a liquid filtered by the device from a blood outlet, thereby converting leukocytes from the leukocyte-containing liquid. It was found that it can be removed with high efficiency.

That is, according to the present invention, (1) a container having a blood inlet at an upper portion and a blood outlet at a lower portion has a capacity of 0.16 g /
In thin leukocyte removal filter filled with leukocyte-removing filter material with a filling density of less than cm ³ to 0.35 g / cm ^3, the packing density of the leukocyte-removing filter material in the region including the right under the blood inlet port, said in the remaining region A leukocyte removal filter device characterized by having a higher density than the packing density of the filter material, (2) an average value of the packing density of the filter material in a region including immediately below the blood introduction port,
The ratio of the packing density in the remaining area to the average value is 1.03.
The leukocyte-removing filter device of (1), which is 1.43 or less, (3) the region where the packing density of the filter material is high is 20 to 30% of the effective filtration area of the leukocyte-removing filter material. The leukocyte removal filter device of (1) or (2), which is a fan-shaped or circular region, and (4) the leukocyte removal filter device of any of (1) to (3) above, wherein leukocytes are passed through a blood inlet. The present invention relates to a method for removing leukocytes from a leukocyte-containing liquid, comprising injecting a liquid containing the liquid and collecting the liquid filtered by the device from a blood outlet.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
1 and 2 show an example of the leukocyte removal filter of the present invention. In the present invention, the thin leukocyte removal filter device refers to an area of an effective filtration portion with respect to a thickness t (cm) of a main filter material (7) that contributes to leukocyte removal among the filled filter materials. Diameter D when converted to a circle of the same area as
A leukocyte removal filter having a ratio (cm) D / t of 5.0 or more. D / t is desirably less than 50.0. When D / t is 6.0 or more and less than 40.0, the effect of the present invention is more likely to be exhibited, and D / t is 7.0 or more and 35.0 or less.
More desirably, it is less than zero.

The leukocyte removal filter is filled with
The main filter material (7) contributing to leukocyte removal is a fiber such as a nonwoven fabric manufactured by a melt blowing method, a flash spinning method, a papermaking method, or the like, or a porous body having continuous pores (a sponge-like structure). ), Porous membranes and the like.

When the base material forming the filter material is made of fiber, the material may be synthetic fiber such as polyamide, polyester, polyacrylonitrile, polytrifluoroethylene, polymethyl methacrylate, polystyrene, polyethylene, polypropylene, or cellulose. Regenerated fibers, purified fibers, semi-synthetic fibers such as cellulose acetate, natural fibers such as hemp, cotton and silk, and inorganic fibers such as glass fibers are all suitable. Furthermore, when using a fiber as a base material, a base material made of a fiber having a substantially uniform fiber diameter may be used, or a plurality of types of fibers having different fiber diameters as disclosed in WO97 / 23266 may be used. The base material in a mixed form may be used. These fibers preferably have an average fiber diameter of 0.01 μm or more and less than 3.0 μm.

When the base material constituting the filter material is a porous material or a porous film, the material may be any of polyacrylonitrile, polysulfone, cellulose, cellulose acetate, polyvinyl formal, polyester, poly (meth) acrylate, polyurethane and the like. Even a material is suitable for the present invention. The average pore diameter of the porous body or the porous membrane is desirably 1 μm or more and less than 30 μm. Further, in the present invention, the filter material may be a base material itself constituting the filter material, or a material whose surface is modified by coating or the like, and both are included in the main filter material contributing to leukocyte removal.

Next, in the present invention, the region where the packing density of the filter material is high and the packing density will be described.
This will be described with reference to FIGS. 1A and 1B and FIGS. 3A and 3B. 20 to 20 of effective filtration area of leukocyte removal filter
The fan-shaped or circular region including the area directly below the blood inlet and having a 30% area is defined as a point on the upper surface of the leukocyte removal filter material immediately below the blood inlet when the blood inlet is at the corner of the container (see FIG. 1A). The inside of a region where the filter material is cut in the thickness direction by a sector (4) drawn so as to be 20 to 30% of the effective filtration area of the filter with the center at 3) is shown, and the blood inlet is at the center of the container. In the case (see FIG. 1b), the circle (4) centered on the point (3) immediately below the blood inlet shows the inside of the area where the filter material is cut in the thickness direction. In addition, the remaining area of the filter material excludes the above-mentioned fan-shaped or circular area corresponding to 20 to 30% of the effective filtration area centered on the center point (3) of the filter surface where blood comes into contact first. Further, it refers to the area (5) of the effective filtration portion of the leukocyte removal filter device. In the present invention, the effective filtration area refers to the area of the filter material through which blood flows when blood is passed through the leukocyte removal filter. For example, in the case of a typical filter as shown in FIG. The area of the upper surface 8 is equal to the cross-sectional area of the filter container.

The average value of the packing density ρ4 (g / cm ³ ) of the region of 20 to 30% of the high density of the present invention and the remaining 70 to 8
The average value ρ5 (g / cm ³ ) of the packing density in the 0% region is
It is obtained as follows. Each area is divided into three to five parts with a substantially equal area, and the average value of the measured packing density in the vicinity of the center of each part is used. The average value of the packing density of the entire leukocyte removal filter material in each area is used. I do. The vicinity of the center of each part divided into three to five parts in a substantially uniform area is, for example, a point (9 to 12) indicated by a cross in FIGS. 3A and 3B. In particular, when measuring the packing density, the peripheral portion of each region, specifically, the portion where the outer peripheral end of the filter material is pressed by the container, and the region (4)
It is preferable to avoid the packing density in a region within about 5 mm from the boundary part of (5) toward the center of the filter material because it cannot be regarded as a representative value of the packing density of the entire filter material.

The packing density of the leukocyte-removing filter material is measured as follows. 1) Take out the leukocyte removal filter material from the leukocyte removal filter device. 2) From the extracted leukocyte removal filter material,
A prism having a 1 cm square cross section including the measurement points indicated by the marks is cut out and the weight is measured. 3) Cut the equivalent leukocyte-removing filter device in the thickness direction so as to include a point (x mark) for measuring the packing density of the filter material, and determine the thickness of the leukocyte-removing filter material in a state of being filled in the filter device. Measure. 4) The packing density is determined by dividing the weight per unit area of the filter material measured in 2) by the thickness of the filter material measured in 3). 5) From the packing density measured for each measurement point,

As described in the above section, the average value in each region is determined, and the average value is used as the average value of the packing density in each region. When the leukocyte removal filter device has a filter such as a prefilter that does not contribute to leukocyte removal, the packing density is not included. In the leukocyte removal filter device of the present invention, both the packing density in the high density region and the packing density in the remaining region are 0.16 g / cm ³ or more and 0.35 g.
/ Cm ³ . The packing density is 0.
If it is less than 16 g / cm ³ , the leukocyte removal ability of the leukocyte removal filter device will be too low, which is not appropriate. If the packing density is 0.35 g / cm ³ or more, erythrocyte passage resistance increases, and the treatment time is prolonged and hemolysis is caused by destruction of the erythrocyte membrane. More preferably, the packing density is 0.17 g / cm ³ or more and less than 0.30 g / cm ³ .

As the technical means for adjusting the packing density of the leukocyte removal filter material, the following technical means can be used. If the container of the leukocyte removal filter device is made of hard plastic, by adjusting the height of the rib molded inside the container, if the container is made of flexible plastic,
From the outside of the leukocyte removal filter device, it can be pressed by a hard plastic or metal jig to adjust the packing density of the filled filter material. Further, the leukocyte removal filter material to be filled may be molded into a desired thickness by heating and pressing in advance, and the molded filter may be filled in a leukocyte removal filter device. Either method can be applied to the present invention.

In the thin leukocyte removal filter device, the average value ρ4 of the packing density of the filter material in a 20 to 30% fan-shaped or circular region (4) including immediately below the blood introduction port in the effective filtration area of the leukocyte removal filter.
(G / cm ³⁾ and the ratio ρ4 / ρ5 between the average value of the remaining 70-80% of the packing density ρ5 (g / cm ³⁾ is desirably 1.03 or more 1.43 or less. When ρ4 / ρ5 exceeds 1.43, the packing density of the leukocyte-removing filter material in the region (5) decreases, so that the leukocyte-removing ability of the filter material itself decreases and the blood passage resistance is low. Most of the blood passes through area (5). As a result, the leukocyte removal rate of the leukocyte removal filter device decreases, which is not preferable. When the packing density ratio ρ4 / ρ5 is less than 1.03, there is almost no difference in the packing density of the leukocyte removal filter material in the regions (4) and (5), and the packing flows in the region (4) near the blood inlet. Since the amount of blood increases, the leukocyte removal filter material in the region (5) is not effectively used for leukocyte removal, which is not preferable. The packing density ratio ρ4 / ρ5 of the leukocyte removal filter material in the leukocyte removal filter device is 1.05 or more and 1.35.
It is more preferably not more than 1.08 and not less than 1.28.
It is more preferred that:

In addition, 20 to 30% including immediately below the blood introduction port
The filling density of the leukocyte-removing filter material from the fan-shaped or circular area (4) to the remaining 70-80% area (5) is as follows:
It may be changed stepwise at the boundary between the area (4) and the area (5), or may be changed continuously. At this time, from the center point (3) of the filter surface to the region (5), the change may be made in a stepwise manner or may be made in a continuous manner, and the manner of making the change is not particularly limited. Blood products to be filtered by the leukocyte removal filter device of the present invention,
Any of whole blood products, red blood cell products, platelet products, plasma products and the like are suitable.

Next, the present invention will be described in more detail and specifically with reference to examples, but the present invention is not limited thereto.

Example 1 N, N-dimethylaminoethyl methacrylate (hereinafter, referred to as DM) and 2-hydroxyethyl methacrylate (hereinafter, referred to as HEMA) were each 1 mol.
V-65 (2,2'-azobis (2,4-dimethylvaleronitrile) manufactured by Wako Pure Chemical Industries, Ltd.) was added as a polymerization initiator to ethanol (special grade) dissolved at a concentration of 1 / L in an amount of 0.01.
mol / L and added under nitrogen atmosphere.
Polymerization was conducted at 4.5 ° C. for 4.5 hours. After the completion of the polymerization, the reaction solution was dropped into distilled water to precipitate a polymer, and then freeze-dried. When the DM content in the obtained polymer was measured by acid-base titration, it contained about 3 mol% of a DM component (hereinafter, referred to as HDM-3).

A polyester fiber having an average fiber diameter of 33 μm
1.0 g of woven cloth and a 13 μm average fiber diameter
0.6 g of ester non-woven fabric on the blood inlet side,
In the lower layer, the average fiber produced by the melt blow method is used.
0.4 g of polyester non-woven fabric with a fiber diameter of about 1.7 μm
Polyester non-woven fabric 1.0 having an average fiber diameter of about 1.3 μm
g has an inlet and an outlet for blood and has an effective filtration cross-sectional area.
Is 3249mm^Two(57mm × 57mm) container
did. The weight of the nonwoven fabric shown here is the
This is the filling weight of the nonwoven fabric corresponding to the area. Blood inlet side
On the inner surface of the filter container, a width of 0.5 mm and a height of about 2 mm
The ribs were provided at intervals of 5 mm, but the height of
By increasing the height by 0.2 mm, leukocyte removal in that part
The thickness of the filter material is 1.9 mm and the thickness of other areas
Was adjusted to 0.21 mm. Of the available filtration area, blood
25% fan (4) including immediately below the liquid inlet in the high density area
did. Of the packing density of the filter material in the high density region
Average value ρ4 (g / cm ^Three) Is 0.23 g / cm^ThreeIn
In the remaining 75% of the area (5).
The average value of the packing density of the luter material ρ5 (g / cm^Three) Is 0.
21g / cm^ThreeMet. That is, leukocyte removal filter
Packing density ratio ρ of leukocyte removal filter material in the device
4 / ρ5 was 1.10. Also the main filter
Effective filtering part for the thickness t (cm) of the material
Diameter D (c
m) The ratio D / t was 24.7. Made in this way
HDE-3 polymer in the leukocyte removal filter device
Ethanol solution dissolved at a concentration of 0.2% by weight at 40 ° C.
, And filled in this container, and allowed to stand for 1 minute. afterwards
Blow off excess liquid with nitrogen gas, then 45 ° C
Filter device by vacuum drying for 16 hours at
Was prepared.

Next, it was confirmed whether or not blood uniformly flowed through the leukocyte removal filter material using the fine particle suspension. A method for preparing the fine particle suspension used for the test will be described. 13.5 g / L of citric acid, 20.4 g / L of sodium dihydrogen phosphate, 3.5 w of polyvinylpyrrolidone (K-90, molecular weight: 360,000 / manufactured by Wako Pure Chemical)
It is prepared by adding to distilled water so as to become t%. Fine particles composed of a polystyrene / divinylbenzene copolymer having an average particle diameter of 2.5 μm were added to this solution so as to be 5650 particles / μL to prepare a fine particle suspension. The prepared fine particle suspension had a pH of 3.6 and a viscosity of 22 mPa · s.

325 g of the prepared fine particle suspension was allowed to stand until it reached room temperature of 24 ° C., and was filtered at a height of 0.7 m using the previously prepared leukocyte removal filter. After the filtration was started and the particulate suspension was filled in the filter, the filtration was performed until the particulate suspension disappeared in the blood bag, and the filtered liquid was collected. At this time, the filtration time was from when the fine particle suspension began to flow out of the outlet of the filter to when the fine particle suspension in the blood bag disappeared.

After filtering the fine particle suspension in this way, the leukocyte removal filter device is disassembled, and the first uppermost layer on the upstream side is taken out of the polyester nonwoven fabric having an average fiber diameter of about 1.3 μm. In the effective filtration area of the leukocyte removal filter, a perfect circular sample (13) having a diameter of 9 mm was cut out from a 25% fan-shaped region (4) immediately below the blood inlet. Similarly, from a substantially central portion of the remaining 75% of the region (5), a completely circular sample (1
4) was cut out. A sample cut into a perfect circle having a diameter of 9 mm was put into a mixed solvent of 1 mL of a 25 wt% aqueous sodium hydroxide solution and 5 mL of dimethyl sulfoxide (DMSO), and gently shaken at 40 ° C. for 16 hours to dissolve the polyester nonwoven fabric. The concentration of the fine particles composed of the polystyrene / divinylbenzene copolymer contained in this solution was determined by counting using a Birkelturk-type hemocytometer. Based on this value, the number of captured fine particles per unit area of the sample cut out was calculated. As a result, the number of captured fine particles of the leukocyte removal filter material was 1.2 in region (4).
× 10 ⁶ / cm ² · sheet, and 1.1 × in area (5)
10 ⁶ pieces / cm ² . Therefore, the difference in the flow rate per unit area of the fine particle suspension is small in the region (4) and the region (5), and it can be estimated that the leukocyte removal filter material is used almost equally in both regions.

Next, the performance of the filter was actually confirmed using blood. 56 mL of ACD-A solution (composition: sodium citrate 2) as an anticoagulant in 400 mL of blood
2.0 g / L, citric acid 8.0 g / L, glucose 2
After centrifuging 456 mL of whole blood prepared by adding 2.0 g / L), the plasma and the buffy coat were removed, and a 95 mL MAP solution (composition: sodium citrate 1.50 g / L, citric acid 0.20 g / L, glucose 7.21 g / L, sodium dihydrogen phosphate dihydrate 0.94 g / L, sodium chloride 4.97 g / L, adenine 0.14 g / L, mannitol 14.57 g / L
L) plus a concentrated erythrocyte preparation (hematocrit is about 64
%) And stored at 4 ° C. for 14 days.

The same value as used above, that is, the average value ρ4 (g / g) of the packing density of the leukocyte-removing filter material in the 25% fan-shaped region (4) immediately below the blood introduction port in the effective filtration area of the leukocyte-removing filter. cm ³ ) is 0.23
g / cm ³ , and the average value ρ5 (g / c) of the packing density of the leukocyte removal filter material in the remaining 75% of the region (5).
m ³ ) is 0.21 g / cm ³ , and 325 g of a concentrated red blood cell preparation is obtained by using a leukocyte removal filter device in which the packing density ratio ρ4 / ρ5 of the leukocyte removal filter material in the leukocyte removal filter device is 1.10. The leukocyte removal performance was evaluated by filtering at a drop of 1 m. At the start of filtration, after connecting the filter to the blood bag containing the concentrated erythrocyte product via the blood circuit, the blood bag is pressurized at 100 mmHg using a bag pressurizer, and the blood is forced into the filter. Was satisfied. Thus, after the filter was filled with blood, the bag pressurizer was removed and filtration was performed until the blood in the blood bag was exhausted, and the filtered blood was collected. The filtration time at this time was from when the blood began to flow out of the outlet of the filter to when the blood in the blood bag was exhausted.

The leukocyte concentration of the concentrated red blood cell preparation before filtration (hereinafter, referred to as a pre-filtration liquid) and the collected concentrated red blood cell preparation (hereinafter, referred to as a recovery liquid), the volume of the pre-filtration liquid and the volume of the recovery liquid are shown below. The leukocyte removal ability was measured according to the following formula. Leukocyte removal ability = -Log {(white blood cell concentration in collected liquid × collected liquid volume) / (white blood cell concentration in filtered liquid × volume of filtered liquid)} Was divided by the specific gravity of the blood product (1.08). The leukocyte concentration of the pre-filtration solution was 10-fold diluted with Turku's solution,
It was measured by injecting into a Birkelturk-type hemocytometer and counting the number of leukocytes using an optical microscope.
The measurement of the leukocyte concentration of the recovered solution was performed by the following method. The recovered solution is used as a leuco plate solution (SOB
5 times with IODA). After thoroughly mixing the diluent, the mixture was allowed to stand at room temperature for 6 to 10 minutes. This is 2,7
After centrifugation at 50 xg for 6 minutes, the supernatant was removed and the liquid volume was adjusted to 1.0
Adjusted to 2 g. After thoroughly mixing the sample solution, the mixture was injected into a nadget type hemocytometer, and the leukocyte concentration was measured by counting the number of leukocytes using an optical microscope. As a result, the filtration time was 15.8 minutes, and the leukocyte removal ability was 4.
26.

[0033]

Comparative Example 1 In a leukocyte removal filter device in which the same amount of nonwoven fabric as in Example 1 was filled, the leukocyte removal filter material in a fan-shaped region (4) just below the blood introduction port in 25% of the effective filtration area of the leukocyte removal filter. Average value ρ4 (g / cm ³ ) of the packing density of 0.23 g / cm
^{In 3} , the average value ρ5 (g / cm ³ ) of the packing density of the leukocyte-removing filter material in the remaining 75% of the area (5) is set to 0.
Adjusted to 23 g / cm ³ . That is, the packing density ratio ρ4 / ρ5 of the leukocyte removal filter material in the leukocyte removal filter device was 1.00.

Example 1 This leukocyte removal filter device was used in Example 1.
The same polymer as in Example 1, ie, HDM-3, was coated by the same operation as in Example 1, and the same operation as in Example 1 was performed to filter the fine particle suspension. The number of captured fine particles of the leukocyte removal filter material was determined. As a result, the number of captured particles of the leukocyte removal filter material was 1.7 × 10 ⁶ / cm ² · in the area (4) and 0.5 × 10 ⁶ / cm ² · in the area (5). Met. Therefore, the flow rate of the fine particle suspension per unit area is about three times larger in the area (4) than in the area (5),
Therefore, it can be estimated that the number of particles captured by the leukocyte removal filter material in the region (4) is about three times as large. That is, the leukocyte-removing filter material is used more in the region (4) for capturing fine particles than the region (5), and the entire leukocyte-removing filter material filled in the same leukocyte-removing filter device is used evenly. It can be estimated that they have not.

The same as that used above, that is, the average value ρ4 (g / g) of the packing density of the leukocyte-removing filter material in the 25% fan-shaped region (4) immediately below the blood introduction port in the effective filtration area of the leukocyte-removing filter. cm ³ )
g / cm ³ , the average value of the packing density ρ5 (g / c) of the leukocyte removal filter material in the remaining 75% of the region (5).
m ³ ) was adjusted to 0.23 g / cm ³ , and the same operation as in Example 1 was performed on a leukocyte removal filter device in which the packing density ratio ρ4 / ρ5 of the leukocyte removal filter material in the leukocyte removal filter device was 1.00. Was performed to filter the concentrated red blood cell preparation. As a result, the filtration time was 16.6 minutes, and the leukocyte removal ability was 3.75. Since the whole leukocyte removal filter material is not efficiently utilized, it can be estimated that the leukocyte removal ability has decreased compared to Example 1.

[0036]

Example 2 The same leukocyte removal filter device as that used in Example 1 was used except that the packing density of the leukocyte removal filter material in region (5) was different. That is, in the effective filtration area of the leukocyte removal filter, the average value ρ4 (g / cm) of the packing density of the filter material in the sector area (4) of 25% immediately below the blood introduction port.
³⁾ is a 0.23 g / cm ^3, the average value ρ5 (g / cm ³ bulk density of the leukocyte-removing filter material in the remaining 75% of the area (5)) is 0.18 g / cm ^3, leukocytes Using a leukocyte removal filter device in which the packing density ratio ρ4 / ρ5 of the leukocyte removal filter material in the removal filter device is 1.27, the same operation as in Example 1 was performed to filter the fine particle suspension, and the area ( The number of captured fine particles of the leukocyte removal filter material in 4) and the region (5) was determined. As a result, the number of captured fine particles of the leukocyte removal filter material was 1.0 × 10 ⁶ / cm ² · in the area (4) and 0.8 × 10 ⁶ / cm ² · in the area (5). Therefore, it can be estimated that the entire leukocyte removal filter material is efficiently used. The same as that used above, that is, the average value ρ4 (g / cm ³ ) of the packing density of the leukocyte-removing filter material in the 25% fan-shaped region (4) immediately below the blood introduction port in the effective filtration area of the leukocyte-removing filter.
To 0.23 g / cm ³ , the average value ρ5 of the packing density of the leukocyte removal filter material in the remaining 75% of the area (5).
(G / cm ³ ) was adjusted to 0.18 g / cm ³ , and the leukocyte removal filter device in which the packing density ratio ρ4 / ρ5 of the leukocyte removal filter material in the leukocyte removal filter device was 1.27 was used. By performing the same operation, the concentrated red blood cell preparation was filtered. As a result, the filtration time was 14.3.
The leukocyte removal ability was 4.02 per minute. It can be estimated that the entire leukocyte removal filter material is efficiently used.

[0037]

Comparative Example 2 The same leukocyte removal filter device as that used in Example 1 was used except that the packing density of the leukocyte removal filter material in region (5) was different. That is, in the effective filtration area of the leukocyte removal filter, the average value ρ4 (g / cm) of the packing density of the filter material in the sector area (4) of 25% immediately below the blood introduction port.
³⁾ is a 0.23 g / cm ^3, the average value ρ5 (g / cm ³ bulk density of the leukocyte-removing filter material in the remaining 75% of the area (5)) is 0.15 g / cm ^3, leukocytes Using a leukocyte removal filter device in which the packing density ratio ρ4 / ρ5 of the leukocyte removal filter material in the removal filter device is 1.53, the same operation as in Example 1 was performed to filter the fine particle suspension, and the region ( The number of captured fine particles of the leukocyte removal filter material in 4) and the region (5) was determined. As a result, the number of captured fine particles of the leukocyte removal filter material was 0.5 × 10 ⁶ / cm ² · in the area (4) and 0.4 × 10 ⁶ / cm ² · in the area (5). Met. Since the packing density (ρ (5) g / cm ³ ) of the leukocyte removal filter material in the region (5) is small, it can be estimated that the number of captured fine particles of the leukocyte removal filter material has decreased.

[0038]

Embodiment 3 ~

Example 6 The same leukocyte-removing filter device as used in Example 1 was used except that the packing density of the leukocyte-removing filter material in region (5) was different from that used in Example 1. The suspension was filtered to determine the number of captured fine particles, and the same operation as in Example 1 was performed to filter the concentrated erythrocyte preparation. The results are shown in Examples 1 to
2 and Comparative Examples 1-2 are summarized in Table 1.

[Table 1]

[0039]

As described above, by making the packing density of the filter material in the area immediately below the blood introduction port of the leukocyte removal filter higher than the packing density of the remaining area, the entire leukocyte removal filter material can be efficiently used. Can,
It has become possible to efficiently exhibit the leukocyte removal ability of the filter material.

[Brief description of the drawings]

FIGS. 1a and 1b are typical schematic diagrams showing the division of a filtration region in the present invention.

FIG. 2 is a typical schematic view showing a cross section of a filter device in the present invention.

FIGS. 3a and 3b are typical schematic diagrams showing locations where the packing density of the leukocyte removal filter material is measured in the present invention.

FIG. 4 is a schematic diagram showing locations where a leukocyte removal filter material is sampled for measuring the number of captured fine particles in Examples and Comparative Examples of the present invention.

[Explanation of symbols]

1: blood inlet 2: blood outlet 3: center point of the filter surface where blood contacts first 4: of the effective filtration area of the leukocyte removal filter
A fan-shaped or circular area with a high packing density immediately below the blood inlet 5: Of the effective filtration area of the leukocyte removal filter,
Remaining area excluding a fan-shaped or circular area with a high packing density immediately below the blood inlet 6: Pre-filter material 7: Leukocyte removal filter material 8: Upper surface of leukocyte removal filter material 9: Typical packing density measurement in leukocyte removal filter material Point 10: Typical packing density measurement point in leukocyte removal filter material 11: Typical packing density measurement point in leukocyte removal filter material 12: Typical packing density measurement point in leukocyte removal filter material 13: Number of trapped fine particles Where the leukocyte removal filter material was sampled for sampling 14: Where the leukocyte removal filter material was sampled for measurement of the number of trapped particles

Continued on front page F term (reference) 4C077 AA12 BB02 EE01 KK13 KK15 LL16 LL22 MM07 MM09 NN02 PP01 PP02 PP08 PP10 PP12 PP13 PP24 4C087 AA01 AA02 AA04 BB34 CA06 DA18 NA14 ZA52 4D006 GA02 HA37 JA02 MC37 MC37 MC48 MC48X MC53 MC62 PA05 PB09 PB45 PC41 4D019 AA03 BA04 BA12 BA13 BB03 BB13 BD01 BD02 CB02 DA03

Claims (4)

[Claims] 1. A container having a blood inlet at the upper part and a blood outlet at the lower part is 0.16 g / cm ³ or more and 0.35 g.
In a thin leukocyte-removing filter filled with a leukocyte-removing filter material at a packing density of less than / cm ^3, the packing density of the leukocyte-removing filter material in a region including immediately below the blood inlet is smaller than the packing density of the filter material in the remaining region. A leukocyte removal filter device characterized by high density. 2. The ratio between the average value of the packing density of the filter material in the region including immediately below the blood inlet and the average value of the packing density in the remaining region is 1.03 or more and 1.43 or less. The leukocyte removal filter device as described in the above. 3. The region according to claim 1, wherein the region where the packing density of the filter material is high is a fan-shaped or circular region having an area of 20 to 30% of the effective filtration area of the leukocyte removal filter material. Leukocyte removal filter device. 4. A leukocyte-removing filter device according to claim 1, wherein a leukocyte-containing liquid is injected from a blood inlet and a liquid filtered by the device is collected from a blood outlet. A method for removing leukocytes from a leukocyte-containing liquid.