JP2003052808A - Filtering method and device for liquid containing white corpuscle - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide filtering method and device capable of lowering pressure loss in filtration to enable high flow speed processing for the blood, and efficiently heightening the white corpuscle removing capability in the case of pressurizing and pouring the blood into a white corpuscle removing filter formed by a flexible container. SOLUTION: This white corpuscle removing filter is formed by a flexible container having an inlet and an outlet and a sheet-like white corpuscle removing filter material disposed to partition the interior of the container into the inlet side and the outlet side. In this filtering method for a liquid containing white corpuscle, the liquid containing white corpuscle is pressurized and poured from the inlet to be filtered at high flow speed with the above filter. A volume constraint plate disposed outside the inlet side and the outlet side of the flexible container is used to constrain the thickness of the white corpuscle removing filter, and at least the face of the volume constraint plate that is opposite to the outer surface on the outlet side of the container is provided with a groove connected to the outlet for a liquid containing white corpuscles. The depth of the groove is above 3 mm.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for filtering leukocyte-containing liquid using a leukocyte removal filter for removing undesirable components such as aggregates and leukocytes from leukocyte-containing liquid. In particular, when the leukocyte-containing filter composed of a flexible container is used to filter the leukocyte-containing liquid at a high flow rate using a pump or the like, the leukocyte-removing filter is prevented from bulging and the thickness of the leukocyte-removing filter is appropriately adjusted. The present invention relates to a method for filtering a leukocyte-containing liquid, which uses a volume restriction plate for holding and uniformizing the flow.

[0002]

2. Description of the Related Art In the field of blood transfusion, so-called leukocyte-removing transfusion, in which contaminated leukocytes contained in a blood product are removed and then the blood product is transfused, has become widespread. This is due to relatively minor side effects such as headache, nausea, chills, non-hemolytic fever reaction associated with blood transfusion, severe alloantigen sensitization, virus infection, post-transfusion GVHD, etc., which seriously affects the recipient. This is because it has been clarified that such side effects are caused mainly by leukocytes contaminated in blood products used for blood transfusion.

[0003] The leukocyte removal method is roughly classified into a centrifugal separation method in which leukocytes are separated and removed by utilizing a difference in specific gravity of blood components using a centrifuge, and a fibrous material and a porous body having continuous pores. There are two types of filter methods that remove white blood cells using a filter material composed of a porous element. The filter method is currently popular because of its advantages such as excellent leukocyte-removing ability, easy operation, and low cost.

The filtering method, that is, the treatment of a leukocyte-containing liquid such as a blood product by a leukocyte-removing filter has often been performed at the bedside when performing a blood transfusion operation, but in recent years, quality control of leukocyte-removing blood products, Also, in order to improve the effectiveness of leukocyte removal treatment, it is becoming common to perform it before storage in a blood center.

Conventionally, a leukocyte-removing filter has been widely used in which a hard container such as polycarbonate is filled with a filter element made of a non-woven fabric or a porous body. 1) Since the container does not have gas permeability, It is difficult to apply steam sterilization, which is widely used as a sterilization process for blood collection sets. 2) When using a so-called closed system in which a leukocyte removal filter is incorporated into a blood collection / separation set and performing leukocyte removal after separating whole blood into a plurality of blood components by centrifugation, the leukocyte removal filter is also used with the blood collection / separation set. Since it is centrifuged, the hard container may damage the bag or the conduit at this time, or the hard container itself may not be able to withstand the stress during centrifugation and may be damaged. In order to solve these problems, a flexible leukocyte removal filter using a flexible material in a container has been developed.

Usually, when filtering blood with these leukocyte removal filters, the bag containing the blood product to be filtered is placed 100 cm higher than the filter and the blood product is filtered by the action of gravity. It is common.

However, in recent years, there is a demand in the market for a leukocyte removal filter to process a desired amount of blood in a short time to shorten the working time.
Therefore, in addition to the conventional method of filtering blood products by the action of gravity, the blood to be filtered is pressurized by a pump or the like and poured into a leukocyte removal filter to increase the blood filtration rate, Methods of filtering blood by time are being investigated.

[0008] As described above, when the filtration method of pressurizing blood with a pump or the like and flowing it into the leukocyte removal filter consisting of a flexible container is performed, a pressure loss occurs due to the resistance of the leukocyte removal filter material during the filtration, The space on the inlet side becomes large positive pressure and the container bulges like a balloon, and the force to peel off the joint is constantly applied to the joint part between the leukocyte removal filter material and the container, which may cause the leukocyte removal filter to burst. It was

As one of the means for preventing such rupture, a method of increasing the pressure resistance by housing a filter made of a flexible container in a reinforcing box or cover made of plastic or the like having a volume smaller than that when expanded But WO90 / 156
60.

However, when a leukocyte removal filter composed of a flexible container is housed in such a reinforced box and blood is pressurized by a pump or the like to flow into the leukocyte removal filter composed of a flexible container, leukocytes are removed. Due to the pressure loss caused by the resistance of the removal filter material, the leukocyte removal filter material is pressed against the container on the outlet side. In such a state, the leukocyte removal filter material comes into close contact with the outlet side container, and the blood flow is obstructed.

Further, Japanese Patent Application Laid-Open No. 2001-149444 discloses an invention in which a filter made of a flexible container is housed in a hard holder. In this hard holder, adhesion between the flexible container and the hard holder is prevented. In order to do so, the inner surface of the holder has a width of 1 mm to 3 mm and a space of 2 mm to 6 m.
It is described that a protrusion such as a rib having a height of m and a height of 1 mm to 3 mm is provided. However, when the present inventor uses this hard holder to pressurize using a pump or the like to filter blood at a high flow rate, the outlet side container on which the leukocyte removal filter material is pressed is provided on the inner surface of the holder. It expands and enters the gap created by the multiple ribs created,
It has been found that it is difficult to prevent the blood flow from being obstructed because a sufficient space for the blood to flow at a high flow rate cannot be created between the leukocyte removal filter material and the outlet side container.

As a method of solving the filter adhesion,
A method to prevent adhesion by inserting a soft PVC tube called a connecting rod between the filter material and the outlet side container (EP0526678)
And a method of preventing the adhesion by making unevenness of height difference 0.2-2 mm on the inner surface of the soft container (JP-A-11-216179), a method of inserting a knit fiber screen or the like (WO95 / 17236) and the like are disclosed. There is. The leukocyte-removing filter made of a flexible container disclosed in these documents is used in WO90 / 15660 and Japanese Patent Laid-Open No. 2001.
No. 149444, the leukocyte-removing filter material is in close contact with the outlet-side container even when it is placed inside the reinforcing box or holder and the blood is filtered at a high flow rate by applying pressure using a pump or the like. It has been found that it is difficult to prevent the blood flow from being obstructed because a space sufficient for blood to flow cannot be created between the leukocyte removal filter material and the outlet side container.

Further, the inner surface of the soft container disclosed in Japanese Patent Laid-Open No. 11-216179 has irregularities with a height difference of 0.2-2 mm,
In the method of preventing the leukocyte removal filter material from coming into close contact with the outlet side container, when the blood is filtered at a relatively low pressure such as filtering the blood product by the action of gravity,
Although effective in reducing the filtration time, it is not effective in improving leukocyte-removing ability.

As described above, according to the conventional technique, in order to filter a large amount of blood in a short time, when a high flow rate filtration method is performed in which the fluid is pressurized by a pump or the like and poured into a leukocyte removal filter composed of a flexible container, It has been difficult to simultaneously achieve 1) reduction of pressure loss during filtration to enable high flow rate treatment of blood, and 2) efficient enhancement of leukocyte removal ability.

[0015]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems, in which high flow rate filtration in which blood is pressurized by a pump or the like and poured into a leukocyte removal filter composed of a flexible container is used. When performed, 1) to reduce the pressure loss during filtration to enable high-velocity blood treatment. 2)
Efficiently increasing the leukocyte-removing ability at the same time.

[0016]

Means for Solving the Problems As a result of intensive studies on a blood filtration method for solving the above problems, the present inventor has found that at least the surface of the leukocyte removal filter that faces the outer surface on the blood outlet side has a flexible container for removing leukocytes. The inventors have found that the above problems can be solved by restricting the thickness of a leukocyte removal filter composed of a flexible container by using a plate having a groove communicating with the blood outlet of the filter, and have reached the present invention.

That is, the present invention provides a leukocyte removal filter comprising a flexible container having an inlet and an outlet, and a sheet-shaped leukocyte removal filter material arranged so as to separate the inside of the container from the inlet side and the outlet side. In the method of filtering the white blood cell-containing liquid, which is applied by pressurizing the white blood cell-containing liquid from the inlet, and filtering at a high flow rate, the white blood cell-containing liquid is arranged outside the flexible container,
The thickness of the leukocyte-removing filter is constrained by using a volume constraining plate having a groove having a depth of more than 3 mm communicating with the leukocyte-containing liquid outlet at least on the surface facing the outer surface of the container on the outlet side. The present invention relates to a method for filtering a leukocyte-containing liquid.

In the present invention, a depth of 3 is provided outside the flexible container.
By providing a volume-constraining plate having a groove communicating with the outlet direction in excess of mm, even when the white blood cell-containing liquid is pressurized and poured in and filtered at a high flow rate, the pressure loss during filtration can be reduced and the high flow rate. It was possible to increase the leukocyte removal ability.

The present invention also provides a volume constraining plate having a groove having a depth of more than 3 mm and communicating in the outlet direction, which is preferably used in a method of filtering a white blood cell-containing liquid which is filtered at a high flow rate while pressurizing. The present invention also relates to a filtration device in which the volume restriction plate is combined with a leukocyte removal filter.

[0020]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention is described in detail below. As the white blood cell-containing liquid to be filtered in the present invention, any liquid containing white blood cells such as whole blood preparation, red blood cell preparation, platelet preparation and plasma preparation is suitable.

The leukocyte-removing filter made of a flexible container referred to in the present invention comprises a flexible container having an inlet and an outlet for blood, and the inside of the container is separated into an inlet side and an outlet side of a leukocyte-containing liquid. Any filter may be used as long as it is a leukocyte removal filter composed of a sheet-shaped leukocyte removal filter material arranged, for example, JP-A-6-335516, JP-A-7-67952, JP-A-7-267871. , Tokuyoudaira 8-507
000, JP 11-216179, EP 0526678, WO9
The leukocyte-removing filter made of a flexible container disclosed in 0/15660 and the like is suitable for the present invention. The sheet-shaped leukocyte-removing filter material is a fibrous structure such as a non-woven fabric manufactured by a melt blow method, a flash spinning method or a papermaking method, a porous body having continuous pores (sponge-like structure), a porous membrane. And so on.

When the base material forming the filter material is a fiber fiber structure, its material is polyamide, polyester, polyacrylonitrile, polytrifluoroethylene, polymethylmethacrylate, polystyrene,
Examples thereof include polyethylene and polypropylene. Further, when the fibrous structure is used as the base material, it may be a base material composed of fibers having a substantially uniform fiber diameter.
23266, different fiber diameters, as disclosed in
It may be a base material in which a plurality of types of fibers are mixed.
These fibers have an average fiber diameter of 0.01 μm or more and 3.0 μm.
It is preferably less than m.

When the base material constituting the filter material is a porous body or a porous membrane, the material can be any material such as polyacrylonitrile, polysulfone, cellulose acetate, polyvinyl formal, polyester, polyacrylate, polymethacrylate, and polyurethane. Even so, it is suitable for the present invention. The average pore size of the porous body or the porous film is preferably 1 μm or more and less than 30 μm. Further, the filter material may be composed of the base material itself, or the surface thereof may be chemically or physically modified, and any filter material contributes to leukocyte removal. A sheet-like leukocyte removal filter. Included in wood. The filter material may be a single layer of a fibrous structure, a porous material or a porous membrane, or may be a combination of a plurality of layers.

In the present invention, to pressurize the leukocyte-containing liquid to flow into the leukocyte-removing filter and to filter at a high flow rate means to pressurize the leukocyte-containing liquid using a blood pump or the like and to increase the flow velocity to flow into the leukocyte filter. Refers to filtering. Place the bag containing the blood product to be processed, which is generally used when treating blood with a leukocyte removal filter, at a position about 100 cm higher than the filter, and remove the blood product by the action of gravity. Filtration at a relatively low load pressure, such as filtration, and a flow rate of 5
Normal hemofiltration flow rates, such as less than 0 mL / min, differ from pressurizing and filtering blood at high flow rates in the present invention. To pressurize blood at a high flow rate in the present invention, a blood pump or the like is placed between the leukocyte removal filter and the bag containing the blood product to be filtered, and the blood pressure is 100 mmHg to 400 mmHg and the flow rate is 100 mmHg to 400 mmHg. 50 mL
It is preferable to transfer the solution to the leukocyte removal filter at a rate of from 200 to about 200 mL / min.

When blood is pressurized at a pressure of less than 100 mmHg, or when it is filtered at a low flow rate of less than 50 mL / min, the expansion of the flexible container on the outlet side of the leukocyte removal filter does not occur even if it is pressure filtered. A small space sufficient for blood to flow at a high flow rate is not formed between the leukocyte removal filter material and the outlet side flexible container. For this reason, the pressure loss during filtration increases and the flow rate of blood to be filtered becomes smaller, which is not suitable. When blood is pressurized at a pressure of more than 400 mmHg or is filtered at a flow rate of more than 200 mL / min, there is a risk of destruction of useful blood components such as destruction of red blood cell membrane, which is not suitable.

The volume constraining plate used in the hemofiltration method of the present invention has at least 3 mm which is in communication with the leukocyte-containing liquid outlet of the leukocyte-removing filter on the surface of the leukocyte-removing filter facing the outer surface of the leukocyte-containing liquid outlet side. It is a plate having a groove having a depth exceeding the limit. The volume constraining plate is preferably arranged so as to sandwich the leukocyte removal filter on both the inlet side and the outlet side of the leukocyte removal filter. The two volume restraint plates on the inlet side and the outlet side may be connected so as to face each other substantially in parallel, but two separate pieces may be used in combination. When two sheets are used in combination, it is more desirable because the space between the volume constraining plates can be easily adjusted by exchanging spacers arranged between the two facing volume constraining plates according to the thickness of the leukocyte removal filter.

In order to pressurize and filter at a high flow rate, the groove depth must exceed 3 mm. When it is 3 mm or less, the leukocyte removal filter material is pressed against the outlet side flexible container at the time of filtration, but since the groove is shallow, it comes into contact with the bottom surface of the groove, so that the area where the flexible container swells is small. You will be restricted. As a result, a sufficient space for the blood to flow at a high flow rate is not formed between the leukocyte removal filter material and the outlet side flexible container, resulting in a large pressure loss during filtration and a low flow rate of blood to be filtered. So not suitable.

The depth of the groove is preferably 6 mm or less. If it exceeds 6 mm, the thickness of the volume constraining plate has to be unnecessarily increased, and the handleability is deteriorated, which is not desirable. More preferably, the groove depth is more than 3 mm and 5 mm or less.

At least the outlet side volume restraint plate is required to have a groove communicating with the leukocyte-containing liquid outlet of the leukocyte removal filter facing the outer surface on the outlet side. The groove is preferably provided on the entire surface of the volume restraint plate. In the present invention, the fact that the groove communicates with the leukocyte-containing liquid outlet means a state in which the liquid that has flowed into the groove can be focused and flowed toward the leukocyte-containing liquid outlet, for example, a leaf vein or a radial shape. It is preferably a groove. If there is a groove that does not communicate with each other, blood tends to stay in that portion, which causes a problem that the leukocyte-removing filter material in that portion cannot be effectively utilized for filtration.

The size of the volume-restricting plate is preferably 80% or more of the effective filtration portion of the leukocyte-removing filter for volume-restricting. If it is less than 80%, there is a risk that the leukocyte removal filter portion protruding from the volume restraint plate will largely swell and burst, which is not preferable. If the size of the volume restraint plate is larger than the leukocyte removal filter,
It is also preferable in that the leukocyte removal filter can be prevented from being greatly swollen by pressurization and the pressure resistance can be improved. The material of the volume restraint plate is any material as long as it can pressurize the leukocyte-containing liquid into the leukocyte removal filter and pressurize the leukocyte removal filter at a high flow rate to withstand the pressure that the leukocyte removal filter largely swells without breaking. May be Examples include hard plastics such as polycarbonate, acrylic, polystyrene, polypropylene, and hard polyvinyl chloride, and hard materials such as metals.

The ratio of the total area of the grooves provided on the outlet side volume restriction plate to the area of the effective filtration portion of the leukocyte removal filter, that is, the occupied area ratio of the grooves provided on the outlet side volume restriction plate is 0.30 or more and 0.97. The following is desirable.
If the occupied area ratio is less than 0.30, when the leukocyte-containing liquid is filtered at a high flow rate by pressurization, the area of the leukocyte-removing filter material that is pressed by the volume constraining plate and adheres to the outlet side container is large. However, it is not suitable because a sufficient space for blood to flow between the leukocyte-removing filter material and the outlet-side container necessary to achieve a high flow velocity cannot be created, and the flow velocity of blood is low. Furthermore, there are many leukocyte-removing filter material portions that are pressed by the volume-constraining plate, and it is difficult for blood to flow through these portions and it is difficult to effectively utilize them for leukocyte removal. As a result, the leukocyte-removing ability decreases, which is not suitable. Further, when the occupied area ratio exceeds 0.97, the intervals of the grooves arranged on the volume restraint plate are too small, and when the flexible container is pressed against the volume restraint plate by pressure,
Since the contact area is too small, there is a high risk of cracking in the flexible container, which is not suitable. Occupied area ratio is 0.40
It is more preferable that it is not less than 0.93 and not more than 0.45
It is more desirable to be 0.90 or less.

The width of the groove provided in the volume constraining plate used in the method of pressurizing blood at a high flow rate of the present invention is 3
It is desirable that it is not less than 15 mm and not more than 15 mm. If it is less than 3 mm, the bulge of the flexible container is small even under pressure filtration, and a sufficient space for blood to flow at a high flow rate is not formed between the leukocyte removal filter material and the outlet side flexible container. . Therefore, the pressure loss at the time of filtration becomes large and the flow velocity of the blood to be filtered becomes small, which is not suitable. Groove width is 15 mm
If it exceeds, the leukocyte-removing filter material is pressed by pressure so that the leukocyte-removing filter material comes into close contact with the inflated flexible container at the same time as the flexible container swells. Is not suitable because a sufficient space for the flow of blood is not formed, resulting in a large pressure loss during filtration and a low flow rate of blood to be filtered. The width of the groove is more preferably 4 mm or more and 12 mm or less, and further preferably 5 mm or more and 10 mm or less.

The interval between the grooves, that is, the width of the portion of the volume restraint plate where the groove is not formed is 0.5 mm or more and 10 m.
It is preferably m or less. If it is less than 0.5 mm, when the flexible container is pressed against the volume constraining plate by pressurization, the contact area is too small and there is a high risk of cracking in the flexible container, which is not suitable. Distance between grooves is 10m
If it exceeds m, the area of the leukocyte-removing filter material that is compressed by the volume restraint plate increases, and such a portion is not utilized for the substantial filtration, so that the pressure loss also increases, the filtration rate decreases, and at the same time, the leukocyte-removing ability decreases. It is not suitable because it decreases. The groove interval is more preferably 2 mm or more and 8 mm or less, and further preferably 3 mm or more and 7 mm or less. The cross-sectional shape of the groove provided in the volume constraining plate may be any shape such as a rectangle, a semicircle, and a triangle.

The interval between the volume restraint plate used on the inlet side and the volume restraint plate used on the outlet side is [thickness of leukocyte removal filter-3 mm] to [thickness of leukocyte removal filter +
5 mm] is desirable. The thickness of the leukocyte-removing filter mentioned here refers to the thickness of the appearance of the filter before filtering blood. When the distance between the inlet side and the outlet side of the volume restraint plate is smaller than the thickness of the leukocyte removal filter by more than 3 mm, the repulsive force of the leukocyte removal filter is large and it is difficult to sandwich the filter between the volume restraint plates. Not suitable for this. When the space between the inlet side and the outlet side is more than 5 mm thicker than the thickness of the leukocyte removal filter, there is a large amount of blood remaining in the leukocyte removal filter after the completion of filtration, and an operation to collect this Is newly required, and the number of complicated operations increases, and at the same time, this operation requires time, which is not desirable. Also, when there is a large amount of blood remaining in the leukocyte removal filter, when rinsing and recovering with physiological saline, etc., the remaining blood and the rinsing liquid used for recovery are mixed, and the remaining blood is efficiently removed. It is not desirable because it cannot be recovered. It is more preferable that the distance between the volume restriction plates on the inlet side and the outlet side is a distance of −2.5 mm to +3 mm of the leukocyte removal filter made of a flexible container, and the thickness of the leukocyte removal filter-2 mm.
It is more desirable that the interval is ˜ + 2 mm.

The groove of the volume constraining plate is not limited to the surface facing the outer surface of the leukocyte-removing filter on the outlet side of the leukocyte-containing liquid,
Furthermore, when it is also provided on the surface of the leukocyte removal filter that faces the outer surface on the inlet side, the effect of further reducing the pressure loss during filtration or increasing the leukocyte removal ability is used only on the surface that faces the outer surface on the outlet side. It is more preferable because it is higher than the case.

Further, it is necessary to set the interval between the volume restraint plate used on the inlet side and the volume restraint plate used on the outlet side so as to be smaller than the thickness of the leukocyte removal filter.
It is desirable for the purpose of reducing the amount of blood loss at the end of filtration.

Next, the present invention will be described in more detail and specifically with reference to Examples, but the scope of the present invention is not limited by these.

[Example 1] A flexible polyvinyl chloride resin sheet having a thickness of 0.04 cm, in which a hole having a diameter equal to or larger than the inner diameters of the inlet and the outlet is formed in a portion where the blood inlet and the outlet are bonded, and an inner diameter of 3 mm , A vinyl chloride tube with an outer diameter of 4.2 mm is welded to the blood inlet and outlet by high-frequency welding, respectively, and the flexible container on the inlet side with the blood inlet and the outlet side with the blood outlet are attached. A flexible container was made.

Next, the following polyester non-woven fabrics were laminated and used. Average fiber diameter is 12μm and basis weight is 30g
/ M ² (nonwoven fabric (1)) 4 pieces, average fiber diameter 1.
7 μm with a basis weight of 66 g / m ² (nonwoven fabric (2)) 2
22 sheets, average fiber diameter 1.2 μm, and basis weight 40 g / m ² (nonwoven fabric (3)) 22 sheets, same as nonwoven fabric (2) 2
A total of 34 sheets, which were the same as the nonwoven fabric (1), were laminated in this order. A laminate composed of three types of non-woven fabrics manufactured as described above was used as 130 mm × 13
It was cut to 0 mm (square). The flexible container and the nonwoven fabric laminate are superposed in this order on the inlet side flexible container, the nonwoven fabric laminate, and the outlet side flexible container, and high-frequency welding is performed so that the size of the filtration portion is 103 mm × 103 mm. A leukocyte-removing filter made of a flexible container was prepared by using the method. The blood inlet side and outlet side conduits were arranged on the diagonal line of the square type leukocyte removal filter. The leukocyte removal filter had a thickness of 9.5 mm.

The above leukocyte-removing filter is arranged between the blood storage bag before filtration and the blood collection bag after filtration,
The inlet-side conduit connected to the pre-filtration blood storage bag was connected to the blood inlet of the leukocyte removal filter, and the outlet-side conduit connected to the post-filtration blood collection bag was connected to the blood outlet of the leukocyte removal filter. Also, as each conduit,
A 3 mm vinyl chloride tube with an outer diameter of 4.2 mm was used.
A Y-tube was attached to the inlet side pipe, and a digital pressure gauge was attached via the pipe. Moreover, a blood pump for pressurizing and delivering blood was attached between the pre-filtration blood storage bag and the Y-shaped tube connected to the digital pressure gauge.

The shape of the volume restraint plate facing the outer surface of the leukocyte removal filter on the blood inlet side is as follows. 17c
4 cm x 4 cm on an acrylic flat plate measuring mx 17 cm
The hole was opened to prevent pressure on the blood inlet side conduit. Further, in order to prevent the blood inlet side conduit from being bent by the volume constraining plate, a groove having a width of 5 mm and a depth of 5 mm was provided along the conduit at a position where the conduit of the volume restricting plate was in contact.

On the other hand, the shape of the volume-constraining plate facing the outer surface on the blood outlet side of the leukocyte removal filter is the same as that of the volume-constraining plate in contact with the outer surface on the blood inlet side, with a groove having the following shape. Is. Width 10 that communicates with a 4 cm × 4 cm hole provided so as not to press around the blood outlet side conduit
A groove having a depth of 5 mm and a depth of 5 mm was provided on a diagonal line. Also, a width of 10 m that communicates with the groove provided on the diagonal line at an angle of 45 degrees.
Grooves with a depth of 5 mm and a depth of 5 mm were provided in a vein pattern on the entire surface of the volume constraining plate at intervals of 5 mm. The occupied area ratio of the grooves installed on the outlet side volume constraining plate was 0.67.

A leukocyte removal filter was placed between these two volume constraining plates and fixed so that the interval between the volume constraining plates was 9 mm. The interval between the volume restraint plates referred to herein is 9 mm on the outer surface on the blood inlet side and the tip portion that is the convex portion between the grooves of the volume restraint plate facing the outer surface on the blood outlet side. It is the distance from the facing volume constraining plate.
The leukocyte removal filter restrained by two volume restraint plates
Blood was filtered by horizontally arranging so that the blood inlet side was on the bottom and the blood outlet side was on the top.

56 as an anticoagulant in 400 mL of bovine blood
mL of ACD-A solution (composition: sodium citrate 22.
0 g / L, citric acid 8.0 g / L, glucose 22.0
456 mL of whole blood prepared by adding (g / L) was centrifuged, plasma and buffy coat were removed, and a red blood cell preservation solution (composition: glucose 22.00 g / L, sodium chloride 9.00 g / L, adenine 0. 27 g / L, mannitol 7.50 g / L) was added to prepare a concentrated red blood cell preparation (hematocrit is about 60%), and the mixture was stored at 20 ° C. for 20 hours.

721 g of the concentrated red blood cell preparation was filtered through the above leukocyte removal filter at a flow rate of 100 mL / min to evaluate the pressure loss value and the leukocyte removal performance. During filtration of the concentrated red blood cell preparation, the digital pressure gauge display was recorded every 50 g of filtered blood, and the highest pressure loss value was recorded. Filtration was performed until the blood in the pre-filtration blood storage bag was exhausted, and the filtered blood was collected. Obtain the white blood cell concentration of the concentrated red blood cell preparation before filtration (hereinafter referred to as the pre-filtration liquid) and the recovered concentrated red blood cell preparation (hereinafter referred to as the recovery liquid),
Thereby, the leukocyte removal ability was compared.

The white blood cell concentration of the pre-filtration solution was measured by diluting it 10-fold with Turk's solution, injecting it into a Birker-Turk type hemocytometer, and counting the number of white blood cells using an optical microscope. The white blood cell concentration of the recovered liquid was measured by the method described below. The recovered solution is diluted 5-fold with a Leuco plate solution (SOBIODA). After mixing the diluent well, it was left at room temperature for 6 to 10 minutes. This was centrifuged at 2,750 g for 6 minutes, the supernatant was removed, and the liquid volume was adjusted to 1.02 g. After thoroughly mixing this sample solution, it was injected into a Nadget-type hemocytometer, and the white blood cell concentration was measured by counting the number of white blood cells using an optical microscope. The amount of blood remaining in the leukocyte removal filter and the conduit after the completion of filtration was calculated from the weight difference between the leukocyte removal filter before and after filtration, and was taken as the blood loss amount.

[0046]

[Comparative Example 1] Except that the volume constraining plate facing the outer surface on the blood outlet side of the leukocyte removal filter had the same shape as the volume constraining plate facing the outer surface on the blood inlet side, that is, one having no groove. The same operation was performed using the same leukocyte removal filter as in Example 1. The occupying area ratio of the grooves installed on the outlet side volume constraining plate is 0.0.

[0047]

[Comparative Example 2] A volume-constraining plate facing the outer surface of the leukocyte removal filter on the blood outlet side is communicated with a 4 cm × 4 cm hole provided so as not to press the circumference of the blood outlet side conduit.
A groove having a width of 6 mm and a depth of 1.5 mm was provided on a diagonal line. Further, grooves having a width of 10 mm and a depth of 1.5 mm, which communicate with the grooves provided on the diagonal line at an angle of 45 degrees, were provided in a vein pattern on the entire surface of the volume constraining plate at intervals of 5 mm. That is, the same shape as in Example 1 was used except that the depth of the groove of the outlet side volume restriction plate used in Example 1 was 1.5 mm, and the same leukocyte removal filter as in Example 1 was used. , The same operation was performed. In Example 1, Comparative Example 1 and Comparative Example 2, the same concentrated red blood cell preparation was used, that is, blood pooled once was divided and used for filtration, and the same concentrated red blood cell preparation was used in Example 1, Comparative Example 1 And Comparative Example 2 were combined as a set and filtered, and n = 4 was evaluated for each. The white blood cell concentration of the pre-filtration solution was in the range of 5,000 to 10,000 cells / μL. The pressure loss during filtration is 200 to 350.
It was in the range of mmHg. N = 4 evaluations each,
The results were averaged, and relative evaluation was performed based on the results of Comparative Example 1 and summarized in Table 1.

[0048]

[Table 1] Pressure loss ratio and residual white blood cell concentration ratio in the recovered liquid

From the above results, in the case of using the volume restraint plate used in Example 1 and performing the high flow rate filtration method in which blood is pressurized with a pump and poured into a leukocyte removal filter composed of a flexible container, 1) filtration At the same time, it was possible to reduce the pressure loss at the time to enable high flow rate treatment of blood, and 2) efficiently enhance leukocyte removal ability.

[0050]

As described above, according to the filtration method, volume constraining plate and filtration device of the present invention, 1) it is possible to reduce the pressure loss during filtration and to process blood at a high flow rate, and 2) remove leukocytes. At the same time, we were able to achieve efficient performance enhancement.

Claims (10)

[Claims] 1. A leukocyte using a flexible container having an inlet and an outlet, and a leukocyte removal filter comprising a sheet-shaped leukocyte removal filter material arranged so that the inside of the container is separated into an inlet side and an outlet side. In a method of filtering a leukocyte-containing liquid, which comprises pressurizing a contained liquid through an inlet and filtering it at a high flow rate, the thickness of the leukocyte-removing filter can be adjusted by using a volume constraining plate arranged outside the inlet side and the outlet side of the flexible container. A method of restraining, wherein the volume restraint plate is provided with a groove communicating with the white blood cell-containing liquid outlet at least on the surface facing the outer surface of the container on the outlet side, and the depth of the groove exceeds 3 mm. 2. The method for filtering a leukocyte-containing liquid according to claim 1, wherein the leukocyte-containing liquid is sent to a leukocyte removal filter at a pressure of 100 mmHg or more and 400 mmHg or less. 3. The leukocyte-containing liquid has a flow rate of 50 mL / min or more 2.
The method for filtering a leukocyte-containing liquid according to claim 1 or 2, which has a flow rate of 00 mL / min or less. 4. The occupied area ratio of the grooves provided in the volume restraint plate is
The method for filtering a leukocyte-containing liquid according to any one of claims 1 to 3, which is 0.30 or more and 0.97 or less. 5. The method for filtering a leukocyte-containing liquid according to claim 1, wherein the width of the groove provided on the volume constraining plate is 3 mm or more and 15 mm or less. 6. The space between the grooves provided on the volume constraining plate is 0.
The method for filtering a leukocyte-containing liquid according to any one of claims 1 to 5, which has a size of 5 mm or more and 10 mm or less. 7. The method for filtering a leukocyte-containing liquid according to claim 1, wherein the depth of the groove provided in the volume restraint plate is 6 mm or less. 8. The distance between the volume constraining plate disposed on the inlet side and the volume constraining plate disposed on the outlet side is [thickness of leukocyte removal filter-3 mm] to [thickness of leukocyte removal filter +
5 mm]. The method for filtering a leukocyte-containing liquid according to any one of claims 1 to 7. 9. A leukocyte using a flexible container having an inlet and an outlet, and a leukocyte removal filter comprising a sheet-like leukocyte removal filter material arranged so that the inside of the container is separated into an inlet side and an outlet side. A volume constraining plate used by being placed outside a container in a method for filtering a leukocyte-containing liquid in which a contained liquid is pressurized at an inlet and filtered at a high flow rate, and a hole through which an inlet or an outlet of the container penetrates. And a groove having a depth of more than 3 mm communicating with the hole. 10. A flexible container having an inlet and an outlet, a leukocyte removal filter comprising a sheet-like leukocyte removal filter material arranged so as to separate the inside of the container into an inlet side and an outlet side, and the container. It is a volume constraining plate that is arranged outside and has a hole through which the inlet or the outlet of the container penetrates, and has a groove with a depth of more than 3 mm that communicates toward the hole. A leukocyte-containing liquid filtration device used for pouring under pressure and filtering at a high flow rate.