JPH0663131A - Method for selectively removing leucocyte - Google Patents

Abstract

PURPOSE:To separate leucocyte from a large quantity of hemocyte floating liquid by simple operation, with good efficiency and by short time processing. CONSTITUTION:If nonwoven fabric prepared from fibers with diameter of less than 3mum and with bulk density from 0.15g/cm<3> to 0.50g/cm<3> or less is used, the contact area with the blood can be increased as compared with the conventional filter, and the longitudinal thickness required for removing leucocyte can be decreased so as to lessen a pressure loss of the filter, so that the above object can be achieved.

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 large amount of blood cell suspension such as blood and body fluid.

[0002]

2. Description of the Related Art In recent years, due to the development of hematology and immunology, in place of conventional whole blood transfusion, attention has been paid to component transfusion that provides only the blood components required by the patient and does not give unnecessary components as much as possible. It is growing. Component transfusions include erythrocyte transfusion, leukocyte transfusion, platelet transfusion, plasma transfusion, and the like, and there are very many cases in which only erythrocytes are transfused to patients with anemia, heart and lung diseases, and the like. As a reason for this, it has been reported that patients transfused with whole blood red blood cell concentrate exhibit side effects such as chills, fever, headache and nausea. It is said that these causes are caused by an immune reaction between the HLA antigen, which is contained in leukocytes in the infused blood, or an antigen called a tissue antigen, and the antibody of the recipient, that is, anti-leukocyte antibody production. Therefore, in the case of transfusion of red blood cells, it is desirable to infuse a concentrated red blood cell liquid in which substances that become antigens such as white blood cells and platelets are removed as much as possible.

Based on these findings, various methods for obtaining concentrated red blood cells from which white blood cells and platelets are removed as much as possible are currently being studied. This method is roughly classified into three types. One is to separate white blood cells, platelets and plasma by centrifugation,
To obtain concentrated red blood cells, two methods are to add dextran to whole blood, sediment the red blood cells, remove plasma containing white blood cells, and then wash away dextran with physiological saline to remove washed concentrated red blood cells. The third method is to obtain leukocyte-depleted concentrated red blood cells by capturing leukocytes with a filter appropriately filled with fibers.

However, the centrifuge method is expensive and requires that washing with physiological saline must be repeated three times or more in order to remove leukocytes and platelets by about 90%. Since the separated red blood cells are aspirated and separated without being aspirated, about 20% of the red blood cells are wasted, but the dextran sedimentation method also requires three times to achieve a leukocyte removal rate of about 90%. It is necessary to wash the physiological saline solution and the dextran as described above, which is time-consuming and difficult to operate.

Japanese Patent Publication No. 58-54125 and Japanese Examined Patent Publication No. 58-54126 are known as methods for capturing leukocytes with a filter device filled with fibers to obtain a red blood cell suspension containing leukocytes free of leukocytes. These inventions provide a leukocyte separation filter device in which at least one kind of synthetic fiber, semi-synthetic fiber, regenerated artificial fiber, inorganic fiber, and natural fiber that does not denature blood is packed in a column at a density of 0.15 g / cm ³ or less. , And a white blood cell separator having an average diameter of 10 μm or less that does not denature blood and is composed of synthetic fibers, semi-synthetic fibers, regenerated artificial fibers, inorganic fibers or natural fibers. The use of a fiber having minute projections on its surface is also disclosed as the fiber, and the diameter converted into a perfect circle with respect to the average diameter (D), that is,
If its weight is xg, its length is ycm, and its density is ρg / cm ³ , then

[0006]

[Equation 1] It is described that it is defined in.

The above-mentioned leukocyte separation filter device and leukocyte separation material are characterized in that they can capture and remove leukocytes from blood with a high degree of purity and yield by simple operations. Speed is 5ml /
It takes about 40 minutes and 50 minutes to process 200 ml.
In addition to the problem that it takes about 100 minutes to process 0 ml and the processing time is too long, there is a problem that if the blood is left at room temperature during the process, the denaturation of the blood will proceed, and further it is extremely important to increase the processing speed. In addition, the capacity of the filter becomes large, and if the fiber is packed to a certain size of 0.15 g / cm ³ or more, there is a problem that the red blood cells are also clogged and the processing speed is extremely reduced.

[0008]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a method for separating and removing leukocytes from a large amount of blood cell suspension with a simple operation, a high efficiency and a very short treatment. .

[0009]

Means for Solving the Problems As a result of intensive investigations by the present inventors in order to achieve the above object, the inventors of the present invention have formed a fiber having a diameter of less than 3 μm and having a bulk density of more than 0.15 g / cm ³ and a density of more than 0.15 g / cm ³ .
When a non-woven fabric of 50 g / cm ³ or less is used, the contact area with blood can be increased as compared with the conventional one, and the thickness in the longitudinal direction required for leukocyte removal can be significantly shortened. Can be smaller,
As a result, they have found that the treatment time can be greatly shortened to about one tenth and that leukocytes can be selectively separated and removed with high efficiency.

According to the present invention, by using the non-woven fabric composed of fibers having an extremely small fiber diameter, the fibers can be uniformly packed in the longitudinal direction and the lateral direction of the filter device. Further, since the fine fibers can be uniformly packed, the packing density can be increased to a level unthinkable with the thick fibers. Therefore, the contact area with the blood cell suspension can be increased, and the length (thickness) in the longitudinal direction required for leukocyte removal can be significantly shortened, that is, can be thinned. As a result, when the blood cell suspension is flowed, The pressure loss of the filter is small, the processing speed is high, and the processing time is short.

Further, by using a non-woven fabric of fine fibers having a diameter of less than 3 μm, the fiber gaps in the filter can be made uniform, uniform and small.
Blood channeling can be prevented, and leukocyte removal performance can be further improved. Furthermore, since the thickness of the filter device can be reduced and downsized, the priming volume can be reduced and the recovery rate of red blood cells can be improved. Also, the processing speed is fast,
When the operation time is short, when the blood stored at 4 ° C. is treated at room temperature, it is possible to prevent the blood temperature from rising and it is also effective in preventing the denaturation of blood. Furthermore, by using a non-woven fabric, there is an effect that the lint generated during the treatment is eliminated and the lint can be prevented from being mixed during the blood transfusion.

The fibers constituting the non-woven fabric filter used in the present invention are synthetic fibers that do not denature blood, such as polyamide, aromatic polyamide, polyester, polyacrylonitrile, polytrifluorochloroethylene, polymethylmethacrylate, polystyrene, Examples include polyethylene and polypropylene. Although it is generally difficult to produce fibers having a diameter of less than 3 μm, there is a melt-blowing process, and by this method, the diameter of the filter used in the present invention is 3
Fibers less than μm can be made. However, the method for producing fibers having a size of less than 3 μm, which constitutes the filter used in the present invention, is not limited to this method.

The non-woven fabric used in the present invention is preferably one in which the fibers are fixed in place by the entanglement of the fibers. As a method for fixing the fiber ring for forming the nonwoven fabric, there is a fixing method by applying heat in the vicinity of the melting point of these fibers to fix them by heat or a fixing method with an adhesive, which can of course be used for the nonwoven fabric used in the present invention. When the fibers become thin like the fibers used in the present invention, the fibers are fixed only by entanglement of the fibers with each other by an air blow method, a high pressure steam blow method or the like, and the non-woven fabric thus created is, for example, destroyed. It is stable as long as it does not exert such a large force, and can withstand blood treatment sufficiently. Therefore, a method of fixing the fibers, which simply entangles the fibers with each other, such as an air blow method or a high pressure steam blow method, which does not completely fix them, is preferably adopted.

The fibers constituting the nonwoven fabric used in the present invention have a diameter of less than 3 μm, preferably 0.1 μm to 3 μm.
It is less than m, and more preferably in the range of 0.1 μm to 2.0 μm. If the diameter of the fiber is smaller than 0.1 μm, it is difficult to make it in practice, but if it is packed evenly, the fiber gap will become too narrow, and red blood cells will be captured together with white blood cells, resulting in clogging and processing speed. Will be extremely reduced. If the fiber diameter is 3 μm or more,
It is necessary to increase the packing density to reduce the fiber gap, and for example, for fibers with a diameter of 3 μm or more, 0.50
Unless the packing density exceeds g / cm ³ , the leukocyte removal rate will decrease. Furthermore, in order to increase the packing density,
It will be filled under high pressure, and the fiber will be broken. Further, since the blood contact area in a fixed volume is small, the volume of the leukocyte removal filter becomes extremely large, which makes it difficult to handle in a hospital.

The nonwoven fabric used in the present invention has a bulk density of 0.1.
It is necessary to exceed 5 g / cm ³ and 0.50 g / cm ³ or less, preferably 0.20 g / cm ³ to 0.30 g.
The range is / cm ³ . Nonwoven fabric bulk density is 0.15g / cm
If it is less than ³ , white blood cells will leak at a high speed of 50 ml / min. When the bulk density of the non-woven fabric is larger than 0.50 g / cm ³ , the fiber gap becomes too dense and red blood cells are also trapped, resulting in a low red blood cell recovery rate.

The thickness of the non-woven fabric used in the present invention is 1 mm to 30 mm, preferably 1 for high-speed treatment of blood cell suspension.
The range is from mm to 20 mm, more preferably from 2 mm to 10 mm. If the thickness of the non-woven fabric is less than 1 mm, the leukocytes are not sufficiently captured and the leukocyte capture rate decreases.
If the thickness of the non-woven fabric is greater than 30 mm, the pressure loss will increase and the processing speed will decrease.

The area of the non-woven fabric filter used in the present invention is
For high-speed processing of the blood cell suspension includes blood inlet side of the total area of 10 cm ² / blood 500ml from 2000 cm ² / blood 500ml including the gap between the fibers, preferably 20 cm ² / blood 500ml from 1000 cm ² / blood 500ml, more preferably in the range of 300 cm ² / blood 500ml of 30 cm ² / blood 500ml. And filter area is less than 10 cm ² / blood 500 ml, since the surface of the leukocyte removal filter comes saturated with leukocytes, processing speed becomes slow. The filter area is 2000 cm ² / blood 50
If it is larger than 0 ml, a large amount of physiological saline is required to collect red blood cells in the white blood cell removal filter after the white blood cell removal treatment, or the number of red blood cells remaining in the white blood cell removal filter increases, resulting in a low red blood cell recovery rate. Come on.

The bulk density of the nonwoven fabric used in the present invention is a value obtained by measuring the weight of a uniform nonwoven fabric per cm ³ . The blood cell suspension referred to in the present invention means blood or body fluid,
For example, in addition to ascites and bone marrow fluid itself, some treatment to these fluids, for example, a hemagglutination suspension obtained by adding a hemagglutination agent such as a hemagglutination agent such as dextran or hydroxyethyl starch, or density gradient centrifugation, etc. A blood cell suspension obtained by such a centrifugation operation, a blood cell suspension obtained by cell electrophoresis, and the like.

In order to selectively capture and remove leukocytes from a large amount of a blood cell suspension, which is the object of the present invention, by a simple operation with a high yield and in a very short time, the fiber diameter is 3 μm.
And the bulk density is more than 0.15 g / cm ³ and 0.50 g
It is necessary to flow a large amount of blood through a filter made of a thin non-woven fabric of not more than 1 cm ³ / cm ³ , preferably the non-woven fabric used is fixed in its position by the entanglement of fibers, and the bulk of the non-woven fabric is large. The density and the filter area are within the above ranges.

The details of the filter used in the method for selectively removing leukocytes of the present invention and the filter device incorporating the filter will be described below with reference to the drawings. 1 and 2 show one embodiment of a filter device used in the method for selectively removing leukocytes of the present invention, and FIGS. 3 and 4 show
9 illustrates another embodiment. In FIG. 1 and FIG. 2, 1 is a filter device main body, and two round tray-shaped frame bodies 2,
2'is fitted with a ring agent 3 so as to form a cavity, and a large number of ridges 4 and 4'are formed on the inner surfaces of the round tray frame bodies 2 and 2 ', respectively. In addition, a filter 6 made of a non-woven fabric is provided between the mesh-shaped support materials 5 and 5 '. Reference numeral 7 is a blood inflow pipe provided in one round tray frame 2, 2 is a blood outflow pipe provided in the other round tray frame 2 ', and 9 and 9'are packings. And
The bulk density of the filter 6 is kept in the range of more than 0.15 g / cm ³ and 0.50 g / cm ³ or less by the mesh-shaped support materials 5 and 5 '.

The filter device of FIGS. 3 and 4 is substantially the same as the filter device, except that a blood inflow pipe 13 and a blood outflow pipe 14 are provided at the central portions of the round tray frames 10 and 10 ', respectively. Mesh support material 1 in the cavity
Filter 12 made of non-woven fabric sandwiched between 1, 11 '
Is provided. 15, 15 'are packings.

The mesh-shaped support member is formed in a mesh shape so that the blood fluid can flow uniformly, and also functions as a flow path regulating portion. Blood is introduced from the blood inflow pipe 7 or 13 and passes through the mesh-shaped support material 5 or 11 to become a uniform flow, and then the filter 6 or 12
The blood which has been introduced into the blood vessel, has leukocytes and platelets trapped therein, erythrocytes and plasma have passed therethrough, and leukocytes have been selectively removed so that the erythrocytes have become thick. By passing through the mesh-shaped support material 5 ′ or 11 ′, , A more uniform flow,
It will be collected from the blood outflow pipe 8 or 14.

The vapor filter selectively captures leukocytes, platelets and the like in blood and allows only red blood cells and plasma to pass through due to the adhesiveness, chargeability, hydrophobicity and fiber gaps of the fiber surface. The effect of tackiness, chargeability, and hydrophobicity of is greatly influenced by fiber gap. White blood cells,
The ability to capture platelets and the ability to pass red blood cells and plasma are related to the bulk density of the nonwoven fabric. According to detailed test results using whole blood of healthy persons, PRC solution, and whole blood of bovine, PRC solution, the bulk density of the non-woven fabric is more than 0.15 g / cm ³ and 0.5.
0 g / cm ³ or less is suitable, and the bulk density of the non-woven fabric made of polyester yarn is 0.20 g / cm ³ to 0.30 g / cm ³
A degree is preferable.

FIG. 5 shows one embodiment of the method for selectively removing leukocytes of the present invention. Blood collected from the human body passes through the circuit 17 by the drop pressure from the blood collection bag 16 and is supplied to the filter device 18 including the leukocyte removal filter of the present invention. The white blood introduced into the filter device 18 is captured by the white blood cell removal filter made of non-woven fabric in the filter device to become white blood consisting essentially of red blood cells and plasma, and after passing through the circuit 19, a collection bag. 20. When the recovery rate of erythrocytes is further enhanced, the erythrocytes partially remaining in the circuit and the leukocyte removal filter can be recovered from the physiological saline bag 21 prepared in advance and similarly introduced into the filter device 18 through the circuit 22. . In addition, 23 is a collection bag and 24 is an adjustment valve. The above shows an example in which blood collected from the human body is contained in a blood collection bag, but blood is directly collected from the human body and introduced into a filter device by a circulation pump or the like to remove red blood cells and the like, red blood cells and plasma. The main blood can be returned to the body again.

As described above, the method for selectively removing leukocytes according to the present invention separates and removes leukocytes from a large amount of blood or hemocyte suspension by a simple operation with high yield and in a very short time. It is possible. Examples will be described below.

[0026]

【Example】

Example 1 A nonwoven fabric in which a polyester fiber having a diameter of 1.2 μm was prepared by a melt-blowing method and a fiber mass having a bulk density of 0.18 g / cm ³ was fixed in its position by the entanglement of the fibers was 110 mm in diameter and thickness. Cut to a 7 mm column shape and have an effective inner diameter of 10
It was fixed in a column having a thickness of 0 mm (effective inner diameter = the diameter of a portion where blood or blood cell suspension actually contacts the filter surface. The same applies to the following Examples) and a column having a thickness of 11 mm. Thirty
Attach the above leukocyte removal filter device at the position of 800 mm drop from each of the 0 ml blood collection bags, and add 8
A 1-liter infusion bag was attached to the lower part of 00 mm to form a collection bag for storing the treated liquid, and a processing device was prepared by connecting the inside with a tube having an inner diameter of 3 mm and an outer diameter of 5 mm. 25 pieces of hematocrit of type A healthy person with fresh CPD solution added to two blood collection bags of this processing device 25 whole blood
The leukocyte-removing treatment was carried out one by one at a room temperature of 25 ° C. by a free fall method using a drop.

Next, 90 ml of physiological saline was flown through this leukocyte removal filter device by the free fall method to collect red blood cells in the filter. As a result, this fresh blood 500
The processing time of ml is 6 minutes and 35 seconds, and the processing speed is 76
The flow rate was as high as ml / min. The leukocyte removal rate is 9
It was 9.7%, and the red blood cell recovery rate was 95%.

Comparative Example 1 Polyester fiber having a diameter of 9.6 μm and a length of 40 mm to 70 mm was placed in a column having a diameter of 30 mm and a length of 100 mm.
A leukocyte removal filter device (bulk density 0.13 g / cm ³ ) in which g was uniformly packed was prepared. Attach the above leukocyte removal filter device at the position of 800 mm drop from each of the 300 ml blood collection bags, and further attach a 1 liter infusion bag 800 mm below to make a collection bag for storing the treated blood, and each of them has an inner diameter between them. 3 mm, outer diameter 5 mm
The processing device connected with the tube of was produced. 250 ml of fresh blood containing 38% hematocrit of fresh type CPD solution of whole blood of type A healthy person is put into 2 blood collection bags of this processing device, and the free fall method using the drop is performed at room temperature at 25 ° C.
The leukocyte removal treatment was performed in order on each bag.

Next, 80 ml of physiological saline was flown through this leukocyte removal filter device by the free fall method to collect red blood cells in the filter. As a result, this fresh blood 500
The processing time of ml was 1 hour 32 minutes 35 seconds, and the processing rate was 5.4 ml / minute. The leukocyte removal rate is 9
The red blood cell recovery rate was 3.2% and the red blood cell recovery rate was 95%. According to Example 1, the leukocyte depletion filter of the present invention is about 14 times as fast as the conventional leukocyte depletion filter, has a good leukocyte depletion rate, and has an excellent red blood cell recovery rate comparable to that of the conventional method. It was a good performance.

Example 2 A non-woven fabric in which polyester fibers having a diameter of 1.8 μm were prepared by a melt-blowing method and fiber lumps having a bulk density of 0.22 g / cm ³ were fixed at the positions by entanglement of the fibers were prepared. , Cut into a cylindrical shape with a thickness of 4 mm and an effective inner diameter of 68 m
It was fixed in a column of m and 8 mm in thickness. Attach the above leukocyte removal filter device at the position of 800 mm drop from each of the 300 ml blood collection bags, and further attach a 1 liter infusion bag 800 mm below to form a collection bag for storing the treated liquid, with the inside diameters between them. 3 mm, outer diameter 5
A processing device connected with a mm tube was created. 250 ml of fresh ACD-A liquid-added whole blood of 42% hematocrit of type B healthy person was put in two blood collection bags of this processing device, and the temperature was 25 ° C at room temperature by a free fall method using a drop.
Then, leukocyte removal treatment was performed one bag at a time.

Next, 40 ml of physiological saline was flown through a leukocyte removal filter device by the free fall method to collect red blood cells on the filter. As a result, the processing time of 500 ml of this fresh blood was 7 minutes and 15 seconds, and the processing speed was as high as 69 ml / minute. The leukocyte removal rate is 100
%, And the red blood cell recovery rate was 98%.

Comparative Example 2 Polyamide fiber (nylon-66) having a diameter of 7.2 μm and a length of 40 mm to 70 mm was used, and a diameter of 36 mm and a length of 70 were used.
A leukocyte removal filter device (bulk density 0.093 g / cm ³ ) was prepared by uniformly packing 6.6 g in a mm column. Three
Attach the above leukocyte removal filter device at the position of 800 mm drop from each of the two 00 ml blood collection bags, and further attach the 1 liter infusion bag 800 mm below to form a collection bag for storing the treated blood, and the space between them is the inner diameter. A processing device connected by a tube having a diameter of 3 mm and an outer diameter of 5 mm was prepared. 250 ml of fresh ACD-A solution-added whole blood of 42% hematocrit of type B healthy person was put into 2 blood collection bags of this processing device, and 1 bag at room temperature 25 ° C by the free fall method using the drop. Leukocyte removal treatment was performed in order.

Next, 80 ml of physiological saline was flown through this leukocyte removal filter device by the free fall method to collect red blood cells in the filter. As a result, this fresh blood 500
The processing time of ml was 1 hour 24 minutes 45 seconds, and the processing rate was 5.9 ml / minute. The leukocyte removal rate is 9
The red blood cell recovery rate was 5.1% and the red blood cell recovery rate was 94%. According to the second embodiment, the leukocyte removal filter of the present invention is about 12 times faster than the conventional leukocyte removal filter, has a good leukocyte removal rate, and has an excellent red blood cell recovery rate comparable to that of the conventional method. It was a good performance.

Example 3 Polyamide fibers (nylon-66) having a diameter of 0.8 μm prepared by a melt-blowing method and having a bulk density of 0.16 g / cm ³ are fixed at their positions by the entanglement of the fibers. The non-woven fabric was cut into a column having a diameter of 100 mm and a thickness of 2 mm and fixed in a column having an effective inner diameter of 90 mm and a thickness of 6 mm.
Attach the above leukocyte removal filter device at the position of 800 mm drop from each of the 300 ml blood collection bags, and further attach a 1 liter infusion bag 800 mm below to form a collection bag for storing the treated liquid, with the inside diameters between them. A processing device connected by a tube having a diameter of 3 mm and an outer diameter of 5 mm was prepared. 250 ml of fresh CPD solution-added whole blood of 45% hematocrit of type A healthy person is put in two blood collection bags of this processing device, and one bag is sequentially placed at room temperature of 25 ° C. by the free fall method using the drop. Leukocyte removal treatment was performed.

Next, 50 ml of physiological saline was flown through this leukocyte removal filter device by the free fall method to collect red blood cells in the filter. As a result, this fresh blood 500
The processing time of ml is 6 minutes 29 seconds, and the processing speed is 77
The flow rate was as high as ml / min. The leukocyte removal rate is 9
It was 9.9%, and the red blood cell recovery rate was 98%.

Comparative Example 3 A leukocyte-removing filter device (bulk density: 0.1 μm) in which a column having a diameter of 80 mm and a length of 40 mm was uniformly packed with 18 g of an acrylonitrile-based synthetic fiber having a diameter of 5.2 μm and a length of 40 mm to 70 mm (bulk density: 0. 090 g / cm ³ ) was prepared. Attach the above leukocyte removal filter at the position of 800 mm drop from each of the 300 ml blood collection bags, and further attach a 1 liter infusion bag 800 mm below to make a collection bag for storing the treated blood, and the space between them is 3 mm inside diameter. , A processing device connected with a tube having an outer diameter of 5 mm was prepared. Two blood collection bags of this processing device were filled with 250 ml each of fresh blood of C-type CPD solution containing 45% hematocrit of type A healthy person, and the temperature was 25 ° C at room temperature by the free fall method.
Then, leukocyte removal treatment was performed one bag at a time.

Next, 210 ml of physiological saline was flown through this leukocyte removal filter device by the free fall method to collect red blood cells in the filter. As a result, this fresh blood 50
The processing time of 0 ml was 19 minutes and 14 seconds, and the processing speed was 26 ml / minute. The leukocyte removal rate is 68.4.
%, And the red blood cell recovery rate was 91.3%. According to Example 3, the leukocyte removal filter of the present invention was a high-speed treatment of 78 ml / min. Although a high-speed treatment was attempted by the conventional method, when the treatment speed was increased to 26 ml / min, the leukocyte removal rate decreased. Therefore, the conventional method has a limit in increasing the processing speed, and high-speed processing as in the present invention cannot be performed.

Example 4 When a nonwoven fabric having a bulk density of 0.28 g / cm ³ prepared by melt-blowing a polyester fiber having a diameter of 2.8 μm was manufactured, a dry heat treatment was performed at 250 ° C. for 2 seconds during the melt-blowing, A non-woven fabric was produced in which the contact points entangled with each other were heat-fixed. This non-woven fabric was cut into a cylindrical shape having a diameter of 160 mm and a thickness of 8 mm and fixed in a column having an effective inner diameter of 150 mm and a thickness of 12 mm. 8 drops each from 2 300ml blood collection bags
Attach the above leukocyte removal filter at the position of 00 mm,
Further, a 1-liter infusion bag was attached 800 mm below to form a recovery bag for storing the treated liquid, and a processing device was prepared in which the collection bag was connected with tubes having an inner diameter of 3 mm and an outer diameter of 5 mm. Two blood collection bags of this processing device, blood concentrated liquid with fresh CPD solution containing 64% hematocrit of an O-type healthy person (part of which plasma was removed by centrifugation)
200 ml each of which was stored at 4 ° C. for 1 day was put into the refrigerator at 4 ° C. by a free fall method using a drop, and immediately, leukocyte removal treatment was performed at room temperature at 10 ° C. one bag at a time.

Next, 220 ml of physiological saline was flown through this leukocyte removal filter by the free fall method to collect red blood cells in the filter. As a result, 400 ml of this fresh blood
Processing time is 6 minutes 27 seconds, and the processing speed is 62 ml.
The flow rate was as high as / min. The leukocyte removal rate is 9
It was 8.9% and the recovery rate of red blood cells was 91%.

Comparative Example 4 Bulk Density of 0.8 μm Made of Polyester Fiber
A 16 g / cm ³ non-woven fabric was cut into a column having a diameter of 100 mm and a length of 6 mm and fixed in a column having an effective inner diameter of 90 mm and a thickness of 10 mm. Attach the above leukocyte removal filter device at the position of 800 mm drop from each of the 300 ml blood collection bags, and attach a 1 liter infusion bag 800 mm below to make a collection bag for storing the treated blood.
A processing device was produced by connecting the spaces with tubes each having an inner diameter of 3 mm and an outer diameter of 5 mm. Blood collection bag 2 of this processing device
A CP of 44% of hematocrit of type A healthy person
250 ml of whole blood added with D liquid was put in each, and leukocyte removal treatment was carried out one bag at a time at a room temperature of 25 ° C. by a free fall method using a drop.

Next, 80 ml of physiological saline was flown through this leukocyte removal filter device by the free fall method to collect red blood cells in the filter. As a result, this fresh blood 500
The processing time of ml is 6 minutes 48 seconds, and the processing speed is 74
The flow rate was as high as ml / min. However, the leukocyte removal rate was low at 75%. The red blood cell 42 rate was 94%.

Comparative Example 5 A non-woven fabric having a bulk density of 0.16 g / cm ³ made of polyester fibers having a diameter of 7.0 μm was used, and the diameter was 100 mm and the length was 6
It was cut into a column of mm and fixed in a column having an effective inner diameter of 90 mm and a thickness of 10 mm. Attach the above leukocyte removal filter device at the position of 800 mm drop from each of the 300 ml blood collection bags, and further attach a 1 liter infusion bag 800 mm below to make a collection bag for storing the treated blood, and each of them has an inner diameter between them. A processing device connected by a tube having a diameter of 3 mm and an outer diameter of 5 mm was prepared. 250 ml of fresh blood with added CPD solution of 46% hematocrit of type A healthy person is put into two blood collection bags of this processing device, and one bag is placed at room temperature at 25 ° C one by one by the free fall method using the drop. The white blood cells were subjected to leukocyte removal treatment.

Next, 80 ml of physiological saline was flown through this leukocyte removal filter device by the free fall method to collect red blood cells in the filter. As a result, this fresh blood 500
The processing time of ml is 5 minutes and 26 seconds, and the processing speed is 92
The flow rate was as high as ml / min. However, the leukocyte removal rate was as low as 58%. The red blood cell recovery was 93%.

Comparative Example 6 Bulk density of 0.4 μm consisting of polyester fibers having a diameter of 2.4 μm
A non-woven fabric of 6 g / cm ³ was cut into a column having a diameter of 100 mm and a length of 6 mm and fixed in a column having an effective inner diameter of 90 mm and a thickness of 10 mm. Attach the above leukocyte removal filter device at the position of 800 mm drop from each of the 300 ml blood collection bags, and further attach a 1 liter infusion bag 800 mm below to form a collection bag for storing the treated liquid, with the inside diameters between them. A processing device connected by a tube having a diameter of 3 mm and an outer diameter of 5 mm was prepared. Two blood collection bags of this processing device, fresh CPD of hematocrit 49% of type A healthy person
250 ml of whole blood added with liquid was put in each, and leukocyte removal treatment was carried out one bag at a time at room temperature of 25 ° C. by a free fall method using a drop. However, the leukocyte removal filter device was clogged and only 25 ml of blood was obtained. When only the obtained blood was analyzed, the leukocyte removal rate was 100% and the red blood cell recovery rate was 5%.

Comparative Example 7 A nonwoven fabric made of polyester fiber having a diameter of 2.4 μm and having a bulk density of 0.05 g / cm ³ was used, and the diameter was 100 mm and the length was 6 mm.
It was cut into a column of mm and fixed in a column having an effective inner diameter of 90 mm and a thickness of 10 mm. Attach the above leukocyte removal filter device at the position of 800 mm drop from each of the 300 ml blood collection bags, and further attach a 1 liter infusion bag 800 mm below to form a collection bag for storing the treated liquid, with the inside diameters between them. A processing device connected by a tube having a diameter of 3 mm and an outer diameter of 5 mm was prepared. 250 ml of fresh CPD solution-added whole blood of hematocrit 46% of type A healthy person is put into two blood collection bags of this processing device, and one bag is placed at a room temperature of 25 ° C one by one by a free fall method using a drop. Leukocyte removal treatment was performed.

Next, 80 ml of physiological saline was flown through this leukocyte removal filter device by the free fall method to collect red blood cells in the filter. As a result, this fresh blood 500
The processing time of ml is 3 minutes and 24 seconds, and the processing speed is 14
The flow rate was as high as 7 ml / min. However, the leukocyte removal rate was low at 63%. The red blood cell recovery was 97%.
The results of each Example and Comparative Example are summarized in Table 1.

[0047]

[Table 1]

[Brief description of drawings]

FIG. 1 is a front view showing an embodiment of a filter device using a leukocyte removal filter of the present invention.

FIG. 2 is a vertical sectional side view showing an embodiment of a filter device using the leukocyte removal filter of the present invention.

FIG. 3 is a front view showing another embodiment.

FIG. 4 is a vertical sectional side view showing another embodiment.

FIG. 5 is an explanatory view showing a mode of use of the filter device using the leukocyte removal filter of the present invention.

[Explanation of symbols]

 1 Filter device body 2, 2'Round tray frame 3 Ring member 4, 4 'Projection 5, 5' Mesh support 6 Filter 7 Blood inflow pipe 8 Blood outflow pipe 9, 9 'Packing 10, 10' Round Tray frame 11, 11 'Mesh-like support material 12 Filter 13 Blood inflow tube 14 Blood outflow tube 15, 15' Packing 16 Blood collection bag 17 Circuit 18 Filter device 19 Circuit 20 Recovery bag 21 Saline solution bag 22 Circuit 23 Recovery bag 24 Adjustment valve

Claims (1)

[Claims] The diameter of the fibers supplying a large amount of the blood cell suspension to one side of the filter the bulk density is from beyond 0.50 g / cm ³ or less of the nonwoven fabric 0.15 g / cm ³ less than 3 [mu] m, to pass to the other side Thus, substantially all the white blood cells in the blood cell suspension are captured by the nonwoven fabric, and the method for selectively removing white blood cells from the blood cell suspension.