JPH0720872B2 - Leukocyte removal filter and leukocyte removal method - Google Patents

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 and a leukocyte removal method. More specifically, the present invention relates to a filter and a leukocyte removal method for removing leukocytes from blood products for transfusion, that is, blood products containing white blood cells such as whole blood, red blood cell products or platelet products.

[0002]

2. Description of the Related Art In recent years, in the field of blood transfusion, so-called leukocyte-removing transfusion has been performed in which contaminated leukocytes contained in blood products are removed and transfused. These are side effects such as headache, nausea, chills, and non-hemolytic fever reaction associated with blood transfusion, and serious side effects such as alloantigen sensitization, which has a more serious effect on recipients, post-transfusion GVHD, and viral infection. However, it has been clarified that it is caused mainly by leukocytes mixed in the blood product used for blood transfusion.

In order to prevent relatively minor side effects such as headache, nausea, chills, and fever, it is necessary to keep the number of white blood cells injected into the recipient in a single blood transfusion to about 100 million or less. For this purpose, it is necessary to remove leukocytes in blood products until the residual rate of leukocytes becomes 10 ^-1 to 10 ^-2 or less. Alloantigen sensitization is one of the most noticeable side effects in the current field of blood transfusion and its prevention is expected. To prevent this, the number of white blood cells injected in one blood transfusion should be adjusted. It is said that it is necessary to suppress the number of cells to 5 million or 1 million or less. For this purpose, it is necessary to remove the residual rate of leukocytes in the blood product to 10 ^-4 or less. About GVHD and virus infection after blood transfusion,
Although there is no established theory yet, like post-transfusion GVHD and cytomegalovirus and adult T-cell leukemia virus,
It is expected that the virus, which is considered to exist only in leukocytes, can be prevented from occurring and infected by removing the leukocyte residual rate to 10 ^-4 to 10 ^-6 or less. Further, it is expected that even with respect to viruses such as HIV that are present in both white blood cells and plasma, the frequency of infection can be reduced by removing the white blood cells.

Methods for removing white blood cells from blood products include:
There are roughly two types: a method of separating by using the difference in specific gravity of red blood cells and white blood cells using a centrifuge, and a filter method of removing white blood cells using a filter using a fiber material or a sponge-like structure as a filter medium. However, a filter method for adsorbing and removing leukocytes by using a non-woven fabric is widely used because it has advantages such as excellent leukocyte removal ability, simple operation, and low cost. .

Most of the leukocyte removal filters using non-woven fabrics have a pre-filter for removing aggregates having an average fiber diameter of about 3 to 30 μm and relatively coarse mesh,
Functionally different main filters for removing white blood cells composed of fibers having an average fiber diameter of about 1.7 to 3 μm 2
It consists of different types of filter elements. Among them, the prefilter preferably has a multi-stage structure in order from the blood inlet to the blood outlet, from a relatively thick and coarse average fiber diameter to a fine and fine average fiber diameter. It is said that (Tokuhei 2-1358)
No. 8, WO 89/03717). Aggregates are formed by aggregating blood-denaturing components containing fibrinogen, fibrin, denatured proteins, nucleic acids and / or fat globules as constituent components, and cell components such as white blood cells and platelets, and are highly adhesive. , Its size is from a few μm to 10
It has a very wide distribution of 0 μm, and sometimes exceeds 1 mm. Therefore, it is necessary to remove large agglomerates first by capturing them with a coarse filter and then gradually reducing the size of the particles to remove smaller agglomerates in a similar manner to separating particles by sieving. is there. In the finest layer of the prefilter used to remove small aggregates, some leukocytes may be trapped as a by-product, but in order to remove leukocytes, it is very small. , The main filters listed below must be used.

White blood cells, which are mainly used for removal, have a diameter of 5
˜20 μm, which has a much more uniform size compared to the aggregates, and the removal mechanism by the filter is considered to be adsorption removal by fibers. The present inventors have previously found that the white blood cell concentration passing through the fiber laminate decreases exponentially with respect to the thickness of the fiber laminate (Japanese Patent Application No. 1-269269), which is a white blood cell. When advancing through the fiber laminate in the thickness direction, it is adsorbed with a certain probability each time it comes in contact with the fiber and the vicinity of the entangled part of the fiber, supporting the above adsorption and removal theory. ing. The confounding part here is defined as follows. That is, the entangled portion is a portion where at least two fibers are in contact with each other in a filter element composed of a large number of fibers, and at least two fibers are three-dimensionally crossed with a minute interval smaller than the diameter of white blood cells. And a portion where at least two fibers are adjacent to each other with an interfiber distance smaller than the diameter of white blood cells.

Therefore, the investigation of the main filter in the conventional leukocyte-removing filter has been carried out mainly by increasing the adsorption probability, that is, by reducing the average fiber diameter, increasing the packing density, or more uniform fiber diameter distribution. Use of a non-woven fabric (Japanese Patent Laid-Open No. 2-203909)
I was concentrated on. On the other hand, H. Prins; USE OF MICROF
IBRE NONWOVENS IN BLOOD FILTRATION, SESSION APPLIC
ATIONS 1-FILTRATION & SEPARATION, INDEX 90 CONGRES
In S, NPBI, The Netherlands., It is necessary to use functionally different filter elements suitable for each of them because granulocytes among leukocytes are removed by adhesion and lymphocytes are removed by sieving mechanism. There is a statement to the effect that a filter element having an average fiber diameter of 5 μm was used for removing granulocytes, and a filter element having an average fiber diameter of 2.5 μm was used for removing lymphocytes.
However, the filter disclosed in this document is large in size, and no consideration is given to the improvement in performance such as increasing the final leukocyte removal rate to 10 ⁻⁴ or less. In fact, a filter element having an average fiber diameter of 5 μm is at the level of a prefilter as described above, and although it removes a part of leukocytes, the document also mentions the function of removing microaggregates at the top. Also, in the filter element having an average fiber diameter of 2.5 μm used for removing lymphocytes, many granulocytes are removed, and the filter element corresponds to the above-mentioned main filter generally used conventionally. Therefore, the average fiber diameter is 5
Removing both granulocytes and lymphocytes with a filter element having an average fiber diameter of 2.5 μm without removing the granulocytes with a μm filter element does not cause any problems. That is, a filter element having an average fiber diameter of 5 μm is not considered to be an essential element for leukocyte removal. In fact, in the document, before reaching a filter element having an average fiber diameter of 2.5 μm, the average fiber diameter is 5 μm. No consideration has been given to the necessity of removing the granulocytes with the filter element of. Further, since the filter element having an average fiber diameter of 2.5 μm corresponds to the main filter that has been generally used conventionally as described above, a high leukocyte removal rate cannot be expected. That is, in this document, in order to increase the leukocyte removal rate, before reaching the filter element having an average fiber diameter of 2.5 μm, which is considered to be the main filter in the document, the average fiber diameter, which is considered to be a prefilter, is 5 μm
There is no intention to remove granulocytes with m filter elements, nor is there any need for it.

[0008]

Recently, as the importance of leukocyte-removing blood transfusion is recognized, a leukocyte-removing filter having a more excellent leukocyte-removing ability, a smaller size, and a smaller inner space volume is required. It has become possible to be. The blood product remaining in the filter after the completion of the leukocyte removal operation is usually discarded together with the filter. Therefore, in order to reduce the amount of blood products that are wasted as much as possible, a filter having a small internal space volume is required. In addition, the inner space volume of the filter here means the inner product of all the space parts in the filter including the void part of the filter element of the filter that houses the filter element.
In addition, regarding the leukocyte removal ability, even with the highest-performance filters known to date, the leukocyte residual rate is 10 ^-3.
The degree was limited, and it was insufficient to prevent the serious side effects mentioned above.

It is generally desirable to keep the amount of blood product discarded with the filter at a low level within 10-15%, for which, for whole blood or red blood cell products, an internal space volume of 35 ml or less per unit, For a platelet preparation, it is preferable to use a small filter having an inner space volume of 20 ml or less per 5 units, but it is impossible for a conventional filter to realize a sufficiently small leukocyte-removing ability and a sufficiently small inner space volume.

[0010] As a method for enhancing leukocyte removing ability,
A person skilled in the art will easily come up with an increase in the main filter or switching to a filter element with a smaller average fiber diameter. When the volume of the main filter is increased, the increase in the volume of the internal space must be suppressed by increasing the packing density of the main filter into the container so that the volume of the internal space becomes equal to or less than the above value. Usually, the upper limit of the packing density is about 0.4 g / cm ³ , and if it is increased more than this, it will be difficult to fill the inside of the container due to the repulsive force of the nonwoven fabric. For example, the non-woven fabric will be crushed into a film and will no longer function as a filter. Therefore, a packing density of 0.4 g /
Whether the main filter is increased within a range of ³ cm ³ or less (according to the research conducted by the present inventors, usually, in order to achieve a leukocyte survival rate of 10 ⁻⁴ or less within this range, an average fiber diameter of 1.6 μm is used.
m) or less), a main filter with a smaller average fiber diameter must be used.

However, in any of these cases, as the leukocyte-removing ability is improved, the pressure loss of the main filter portion at the time of passing the blood product increases, and before the expected blood volume is processed, However, there is a problem that the processing speed is extremely reduced.

[0012]

As described above, according to the knowledge of the present inventors, when a blood product is passed through a fiber laminate, the concentration of white blood cells passing through the fiber laminate is changed to the thickness of the fiber laminate. On the other hand, it decreases exponentially. It was also found that the degree of this decrease was larger as the average fiber diameter was smaller and the packing density was higher. Therefore, in order to enhance leukocyte removal capacity within a limited internal space volume, the main filter may be replaced with a fiber having a small average fiber diameter or the packing density may be increased. If it is attempted to increase the blood pressure to 10 ^-4 or less, the pressure loss of the main filter portion at the time of passing the blood product increases due to the improvement of the leukocyte removal ability as described above, and the expected blood volume is processed. Before the end, it became clear that the processing speed was extremely reduced. The inventors of the present invention have diligently investigated factors that increase the pressure loss of the filter in order to clarify the cause of this problem, and as a result, surprisingly, the main factor thereof is clogging of leukocytes. I found it.

Up to the present invention, the pressure loss of the filter is basically the viscous resistance of the blood passing through the filter, and the increase in the pressure loss accompanying the treatment of blood is originally caused by clogging of aggregates. It was a conventional finding that this is caused by an increase in the linear velocity of blood in the remaining voids as a result of the blocking of the voids that can pass through. Further, it has been known from the time when cotton-like fiber masses were used for leukocyte removal filters that the use of fibers having a small average fiber diameter resulted in an extremely low flow rate and that the same problem would occur even if the packing density was increased. However, in this case, the flow velocity was low from the initial stage of blood treatment, and as the present inventors confronted this time, this was a phenomenon that was clearly different from the problem of a sudden decrease in velocity during blood treatment. . That is, the problem at that time was
This is caused by the fact that the viscous resistance of blood is extremely increased by using a cotton-like fiber lump to reduce the diameter or increase the packing density, and as disclosed in Japanese Patent Publication No. 2-13587.
This problem has been solved by using a non-woven fabric as a filter material. In the past, in leukocyte removal filters made of non-woven fabric with a residual leukocyte residual rate of about 10 ⁻³ or less, excessive viscous resistance of blood has never been a problem, and pressure loss or flow velocity is a problem. If there is a problem, especially when treating old blood that has been stored for a long time, clogging occurs with aggregates that increase with storage, which causes an increase in pressure loss or during the course of blood treatment. It was a decrease in processing speed. However, this problem is also 2-1358
As disclosed in No. 8, the problem was solved by using a prefilter for removing aggregates, and it was widely put into practical use.

[0014] This problem that we had to solve, is the first problems encountered in an attempt to increase the leukocyte residual rate up to 10 ^-4 or less, a further 10 ^-4 or less leukocyte residual rate of very low concentration of white blood cells After that, the fact that the white blood cell concentration decreased exponentially with respect to the thickness of the fiber laminate was found, and the actual condition became clear. That is, the conventional 1.8-2.
It consists of a main filter of about 5 μm and has a leukocyte residual rate of
As long as a filter of about 0 ^-3 was used, no increase in pressure loss due to clogging of white blood cells was found, and therefore the occurrence of this problem could not be predicted.

In the course of reaching the present invention, the inventors of the present invention used non-woven fabrics having various average fiber diameters, and
Factors that are usually taken into consideration when designing leukocyte removal filters, such as the filtration cross-sectional area and thickness of the filter, were investigated, but this problem could not be finally solved as long as a single main filter was used. As a result of repeated and careful observation of the decreasing behavior of white blood cell concentration with respect to the thickness of the main filter and the pressure loss behavior with respect to blood throughput under these various conditions, surprisingly, the increase in pressure loss was found to be that leukocytes were the most upstream of the main filter. It became clear that this occurs because it is adsorbed on a part and narrows the void.

As described above, the number of white blood cells passing through the main filter exponentially decreases with respect to the thickness of the main filter. Therefore, the number of white blood cells that come into contact with the blood product at the upstream side is larger. Adsorb white blood cells. Therefore, when the main filter is increased in volume and compressed to increase the packing density, more than the same white blood cells as before compression are adsorbed by the compressed filter whose porosity is reduced. It is considered that the clogging of the main filter, especially on the upstream surface of the filter, is significantly increased compared to before the compression, and the pressure loss is significantly increased. Also, when using a main filter with a small average fiber diameter, the pores are originally narrow and the viscous resistance when blood passes through is high, and the leukocyte removal capacity per unit thickness is high, so the leukocytes are severely clogged and the pressure loss is high. Is significantly increased. This phenomenon is a phenomenon that is notably found only when an attempt is made to achieve a certain leukocyte-removing capacity or higher when the packing density is increased or a nonwoven fabric having a small average fiber diameter is used in order to enhance the leukocyte-removing capacity. White blood cell survival rate 1
Designed for performance of 0 ^-3 , the average fiber diameter is relatively large (1.7 to 3.0 μm) and the packing density is low (0.2
It was not observed with the filter (g / cm ³ or less). The essence of this problem is that leukocyte adsorption is concentrated in the upstream part of the main filter with a high packing density and small average fiber diameter, especially in the uppermost layer, which is essential for high performance.

The inventors of the present invention have conducted extensive studies to solve this problem. As a result, among the filter elements incorporated in the leukocyte-removing filter, the main filter portion composed of ultrafine fibers for leukocyte removal was Among them, the first filter element having a relatively small average fiber diameter and the second filter element having a relatively large average fiber diameter are configured in at least two stages, and the blood product passes through the second filter element first, And by this stage 60 of white blood cells
Design a filter element upstream of the blood containing the second filter element such that more than 100% of the first filter element is removed,
It has been found that by configuring the filter such that the blood product passes through the filter element of 1., an extremely high leukocyte-removing capacity can be achieved without causing clogging. It was also found that the filter having the above-mentioned structure can be remarkably miniaturized by applying it to a filter having a currently prevailing level (white blood cell residual rate of 10 ^-2 to 10 ^-3 ). Further, at least 60% of the total number of white blood cells in the blood product to be treated is removed by using a centrifugation method or a known leukocyte removal filter to obtain a poor white blood cell product, and the poor white blood cell product is further subjected to the above-mentioned first. It has been found that by treating with a leukocyte depletion filter having one filter element, it is possible to obtain a blood product having an extremely low leukocyte residual rate without causing clogging of the leukocyte depletion filter.
The present invention has been made based on these findings.

Therefore, one object of the present invention is to have a high leukocyte-removing ability with a leukocyte residual rate of 10 ^-4 or less capable of preventing allosensitization, and at the same time, reduce the amount of blood products to be discarded together with the filter by 10 to 10. Small leukocytes with a filter inner volume of 35 ml or less per unit for whole blood or erythrocyte preparations and a filter inner volume of 20 ml or less per 5 units for platelet preparations to keep the level within 15%. To provide a filter. Another object of the present invention is to provide a leukocyte depletion filter which has a leukocyte residual rate equivalent to that of leukocyte depletion filters currently in widespread use and which has been remarkably miniaturized. Still another object of the present invention is to provide a leukocyte removal method capable of removing leukocytes to a leukocyte residual rate of 10 ⁻⁴ or less in leukocyte-containing blood products.
That is, according to one aspect of the present invention, there is provided a leukocyte removal filter comprising a plurality of filter elements having different average fiber diameters, the first filter element having an average fiber diameter of 0.3 to 1.6 μm. And a second filter element having a larger average fiber diameter than the first filter element, which removes 60% or more of the white blood cells in the blood to be treated, is upstream of the blood to be treated more than the first filter element. There is provided a leukocyte removal filter characterized in that it is arranged on the side.

According to another aspect of the present invention, the white blood cells having the first filter element having an average fiber diameter of 0.3 to 1.6 μm after removing 60% or more of the white blood cells in the blood to be treated are provided. There is provided a method for removing leukocytes from a blood product containing leukocytes, which further removes leukocytes by a removal filter.

The first filter element and the second filter element used in the filter and method of the present invention are composed of one or a plurality of fiber cloth layers made of non-woven fabric or woven cloth, and each layer of the plurality of fiber cloth layers. Is a fiber cloth structure having an average fiber diameter of substantially the same as the average fiber diameter of the entire multi-fiber cloth layer. Further, the non-woven fabric means a cloth-like one in which an aggregate of fibers or threads is chemically, thermally, or mechanically bonded to each other without depending on the knitted fiber. Note that when a certain shape is maintained by friction between fibers and the fibers being in contact with each other, or by being entangled with each other, this is also included in being mechanically coupled. Woven cloth, as it is generally defined, means a cloth formed by interlacing warp yarns and weft yarns. It is also possible to adopt a structure in which the first filter element and the second filter element are respectively constituted by the downstream portion and the upstream portion of one layer which cannot be peeled off.

In the filter and method of the present invention,
The first filter element has an average fiber diameter of 0.3 to 1.6
It is necessary that the thickness is 0.5 μm, and preferably 0.5 to 1.4 μm. More specifically, for a whole blood or red blood cell preparation, 0.7 to 1.3 μm is more preferable, and 0.7 to 1.0 μm is further more preferable. Further, for platelet preparations, 0.5 to 1.0 μm is more preferable, and further 0.5 to 0.8 μm is more preferable.

If it is less than 0.3 μm, it is difficult to stably manufacture a nonwoven fabric, and the viscous resistance of blood becomes too high, which is not suitable. Further, those having a particle size of more than 1.6 μm have a low leukocyte-removing ability for use as the first filter element used in the filter of the present invention, and unless the packing density is 0.4 g / cm ³ or more, the desired internal space volume is obtained. I am not satisfied because I cannot be satisfied.

The average fiber diameter in the present invention means
A value obtained by the following procedure. That is, a portion of the filter element is sampled and photographed using a scanning electron microscope. At the time of sampling, the effective filtration cross-sectional area portion of the filter element is divided into squares each having a side of 0.5 cm, and 6 points are randomly sampled from the section. In order to perform random sampling, for example, after designating an address to each of the above-mentioned sections, it is sufficient to select a required section by a method such as using a random number table. In addition, the first three sections were sampled for the upstream surface and the remaining three sections.
As for the division, the central part of the downstream side surface is magnified 2
Take a picture at 500 times. For each of the sampled sections, photographs of the central portion and the vicinity thereof are taken, and the photographs are taken until the total number of fibers taken in the photograph exceeds 100 and the number becomes the smallest. The diameters of all the fibers shown in the photograph thus obtained are measured. Here, the diameter means the width of the fiber in the direction perpendicular to the fiber axis. The value obtained by dividing the sum of the diameters of all the fibers measured by the number of fibers is taken as the average diameter. However, if multiple fibers are overlapped with each other and the width cannot be measured due to the shadow of other fibers, or if multiple fibers are melted and become thick fibers, the diameters are further significantly different. In the case of mixed fibers, etc., these data are deleted. If the mean fiber diameters on the upstream side and the downstream side are clearly different, this is no longer accepted as a single filter element. Here, "apparently different average fiber diameters" refers to the case where a statistically significant difference is recognized. In this case, the upstream side and the downstream side are regarded as different filter elements, the boundary surface between them is found, and then the average fiber diameters of both are measured separately.

In the filter and method of the present invention, it is necessary to remove at least 60% of the total white blood cells in the blood product to be treated in advance of the first filter element, which is preferable. Is 60 ~
99%, and more preferably 85-99% is removed. When the leukocyte removal rate is less than 60%, the clogging of leukocytes in the first filter element is not sufficiently improved, which is not suitable. That is, the second filter element used in the filter of the present invention is obtained by removing plasma from 1 unit of whole blood containing CPD solution in an amount necessary for anticoagulation of whole blood until the hematocrit reaches about 67%. When filtering the red blood cell concentrate, it is necessary to be able to remove at least 60% of the white blood cells of the total white blood cell count.

In the filter of the present invention, the second
It is necessary for the filter element of No. 1 to have a larger average fiber diameter than that of the first filter element.
It is preferably 2.0 μm and 1.2 times or more the average fiber diameter of the first filter element, and more specifically,
1.5-1.8 μm for whole blood or red blood cells
However, for platelet products, 1.0 to 1.5 μm is preferable. If the ratio of the average fiber diameter of the second filter element to the average fiber diameter of the first filter element is less than 1.2, only the difference in packing density causes the first
The filter element of No. 1 and the second filter element must be designed so as to be functionally different from each other, which is unsuitable because the designable range is limited.

In the filter of the present invention, the first
The average pore size of the filter element is preferably 2 to 18 μm, more preferably 4 to 12 μm. The average pore size of the second filter element is preferably 4 to 25 μm, more preferably 6 to 20 μm.
Is more preferable. The average pore size in the present invention means
Minimum unit of filter element before filling into container (1 sheet)
Mean Flow Pore measured by Coulter Porometer II.
Size). The average pore size is an index that seems to be related to the degree of entanglement of fibers constituting the filter element and the size of voids, but it is not always theoretically supported, and therefore the cause is not clear. If the range is deviated, the suitable balance between the pressure loss and the leukocyte-removing ability may be lost, and the range is preferably within this range.

It is also necessary that the first and second filter elements are constructed so that the blood product passes through the second filter element and then through the first filter element. A separate filter layer, which is a laminate of the two or more layers, or the upstream part of one non-peelable layer satisfies the condition of the second filter element, and the downstream part satisfies the condition of the first filter element. It may be one. Further, in a filter having three or more kinds of filter elements having different average fiber diameters, which are laminated in order from the one having a large average fiber diameter from the upstream side to the downstream side, any two of them If the elements satisfy the requirements of the present invention, they correspond to the first and second filter elements referred to in the present invention. Further, in the filter of the present invention, in addition to the main filter composed of the first and second filter elements described above, a known pre-filter may be laminated on the upstream side, or on the downstream side of the first filter element. Average fiber diameter 0.3 to
It is also possible to arrange the third, fourth, ... Filter elements so that the average fiber diameter becomes smaller within the range of 1.6.

Further, in the leukocyte removal method of the present invention,
When removing 60% or more of leukocytes, a centrifugal separation method or a known leukocyte removal filter may be adopted, or these may be incorporated into one device to be a system, and leukocytes may be contained in one container. It may be carried out by incorporating a filter element composed of fibers having an average fiber diameter larger than that of the first filter element, the filter element having an ability of removing 60% or more of

The present invention is a small-sized filter having a high leukocyte-removing ability as described above, and more specifically, has a high leukocyte-removing ability with a leukocyte residual rate of 10 ⁻⁴ or less which can prevent allosensitization.
At the same time, reduce the amount of blood products discarded with the filter to 1
In order to keep it at a low level within 0 to 15%, for erythrocyte preparations, the internal space volume per unit is 35 ml or less,
20 ml of internal space volume per 5 units for platelet products
The following provides a particularly suitable technical means for designing a small filter, and the present technology is applied to the leukocyte residual ratio of 10 ^-2 to 10
^-If it is applied to a popular leukocyte removal filter of about ^-3 , it is possible to provide a smaller filter with a pressure loss equivalent to the conventional one, or an internal space volume equivalent to the conventional one with a smaller pressure loss. A filter can be provided.

According to the present invention, a leukocyte removal rate for whole blood or erythrocyte preparations has a leukocyte residual ratio of 10 or less.
-If it has a high performance of ^-4 or less, the internal space volume per unit is 15 to 35 ml, and the effective filtration cross-sectional area is 20 to 110.
cm ^2, preferably the inner space volume 20 to 30 ml, effective filtration small cross-sectional area of 25~95cm ^2, is and that of high performance can be realized. In addition, the white blood cell residual rate is 10 ^-2 to 1
If it is a popular type of 0 ^-3 , the internal space volume is 7-1.
8 ml, effective filtration cross-sectional area 10-65 cm ² , preferably internal space volume 7-15 ml, effective filtration cross-sectional area 10-
55 cm ² , more preferably the inner space volume is 10 to 15 m
It is possible to realize a small product having an effective filtration area of 20 to 55 cm ² .

As a leukocyte-removing filter for a 5 unit platelet preparation, if the leukocyte residual rate is 10 ^-4 or less, a high-performance leukocyte removing filter has an internal space volume of 6 to 20 ml and an effective filtration cross-sectional area of 3 to 108 cm. ² , preferably the internal space volume is 6
˜15 ml, effective filtration cross-sectional area 3 to 81 cm ² , more preferably internal space volume 6 to 10 ml, effective filtration cross-sectional area 5
It is possible to realize a compact and high-performance product of ~ 54 cm ² . If the leukocyte residual rate is about 10 ⁻² to 10 ⁻³ , it is a popular type and has an internal space volume of 3 to 8 ml and an effective filtration cross-sectional area of 3 to 43 cm ² , preferably an internal space volume of 3 to 6.
It is possible to realize a small one having an effective filtration cross-sectional area of 5 to 32 cm ² .

If the inner space volume is below the respective lower limit values described above, the pressure loss tends to increase or the treatment time tends to increase even with the effects of the present invention, which is not preferable. On the other hand, exceeding the upper limit of the internal space volume is not preferable because the amount of each blood product discarded together with the filter increases. If the effective filtration area falls below the lower limit of each of the above, the clogging of white blood cells in the first filter element cannot be ignored, and the viscous resistance of blood increases as the linear velocity increases during blood treatment. It is not preferable because it increases. On the other hand, when the effective filtration area exceeds each upper limit value, the filter thickness must be extremely thin in order to keep the internal space volume within a predetermined range. Moreover, it is not preferable to fill each filter element in an amount necessary to obtain each target leukocyte-removing ability, because the packing density becomes extremely high and the manufacturing becomes more difficult.

The packing density of the main filter is
It is preferable that both the second filter element and the second filter element have a weight ratio of 0.1 to 0.4 g / cm ³ , and further 0.15 to 0.38 g / cm ^3.
3 is preferred and the first filter element is further 0.25
Most preferred is 0.38 g / cm ³ . 0.1 g / cm ³
When it is less than 1, the number of entangled portions between fibers, which are sites for adsorbing leukocytes, is small, and there are problems in handleability and performance stability, which is not preferable. On the other hand, the reason why 0.4 g / cm ³ or more is not preferable is that the production becomes difficult as described above.

The A value of the first filter element described below is preferably in the range of 0.1 to 0.5, more preferably in the range of 0.15 to 0.4, Furthermore, the range of 0.22-0.35 is more preferable. A
Value = packing density (g / cm ³ ) / average fiber diameter (μm) A
When the value is smaller than 0.1, the leukocyte-removing ability tends to be low, which is not preferable, and when the value is larger than 0.5, the viscous resistance of blood tends to increase, which is not preferable.

In the present invention, one unit of whole blood is 40
0 to 500 ml (The blood volume defined as 1 unit of whole blood varies depending on the country, for example, 400 ml in Japan and 5 in Germany.
(00 ml, 450 ml in the United States, France, etc.) was collected blood with an anticoagulant such as CPD, CPDA, or ACD added, and 1 unit of red blood cell preparation means 1 unit of whole blood or part of plasma or It refers to a red blood cell concentrate prepared by removing platelet-rich plasma, and a red blood cell concentrate added with a red blood cell preservative such as Adsol, Neutricel, SAGM or MAP. Further, 5 units of platelet preparation refers to an apheresis platelet preparation containing 5 times the amount of platelet concentrate prepared from 1 unit of whole blood as one unit, or the amount corresponding to the 5 times amount.

First and Second in the Filter of the Present Invention
Each of the filter elements may be preformed by a known method so as to have a predetermined thickness and density before being housed in a container. May be preformed in. Specific examples of the filter element in the present invention include:
Examples include melt blown nonwoven fabrics, flash nonwoven fabrics, spunbonded nonwoven fabrics, spunlaced nonwoven fabrics, wet nonwoven fabrics, dry nonwoven fabrics, needle punched nonwoven fabrics, and the like, as well as paper, woven fabric, mesh, and the like. Further, to give examples of fiber materials, polyamide, aromatic polyamide,
Examples thereof include synthetic fibers such as polyester, polyacrylonitrile, polytrifluorochloroethylene, polymethylmethacrylate, polystyrene, polyethylene and polypropylene, and regenerated fibers such as cellulose and cellulose acetate. Further, in the present invention, known surface modification may be carried out in order to enhance the leukocyte-removing ability of the filter element and, if necessary, the platelet-removing ability (The Role).
of Leukocyte Depletion in
Blood Transfer Practi
ee. Proceedings of the Int
international Workshop, London
n, 9 July 1988, B.I. Brozovic:
p. 38, Blackwell Scientific
Publications, oxford, London
on. ). Further, in order to efficiently adsorb leukocytes to the filter element and allow most of the platelets to pass through, known surface modification may be carried out (EP0267286).

[0037]

EXAMPLES The present invention will be described in more detail with reference to examples. The packing density of the filter element in the present invention is a value obtained by dividing the weight of the filter element with respect to the effective filtration area of the filter element in the state of use by the (effective filtration area x thickness) of the filter element. Is. The volume of the filter's inner space is increased by injecting a liquid such as water, physiological saline solution or alcohol aqueous solution from the inlet of the filter and expelling the air inside the filter, and then sealing the inlet and outlet of the filter to increase the weight of the filter. Minutes are measured, and this value is divided by the specific gravity of the injected liquid.

Example 1. Prefilters with average fiber diameters of 32 μm and 13 μm
2 types of spunbonded nonwoven fabrics with an average packing density of 0.28
g / cm ³ , a total thickness of 1.1 mm was filled in a container having an effective filtration area of 67 mm × 67 mm, and the average fiber diameter of 1.80 μm, average as the second element of the main filter was provided on the downstream side in the same container. Polyester melt blown non-woven fabric with pore size 10.2 μm, packing density 0.26 g / c
m ³ and a thickness of 3.0 mm, and a polyester meltblown non-woven fabric having the same average fiber diameter of 1.23 μm and average pore size of 9.5 μm as the first filter element on the downstream side thereof with a filling density of 0.32 g / cm
³ , a leukocyte removal filter was prepared by filling it to a thickness of 2.0 mm (A value of the element of the first filter was 0.26). The internal space volume of this filter is 32.4 m
1, effective filtration area is (6.7 cm) ² = 44.9 cm ^3.
Met.

From 513 ml of whole blood prepared by adding 63 ml of CPD to 460 ml of blood, 243 ml of platelet-rich plasma was removed by centrifugation within 8 hours after blood collection, and the blood was stored at 4 ° C. for 3 days. Add salt water 3
Red blood cell preparation made up to 60 ml (hematocrit 63%)
Was left at room temperature (26 ° C.) until it reached 25 ° C., and then filtered through the above filter. To start filtration,
After connecting the filter to the blood bag containing the red blood cell preparation via the blood circuit, the blood bag was pressurized to forcibly fill the filter with blood.

After the blood was thus filled in the filter, the peristaltic pump (manufactured by Ato Co., Ltd., Japan) was used to continuously flow at a constant flow rate of 15 ml / min, and the pressure loss due to filtration was measured with a digital pressure gauge. . When the blood in the blood bag is exhausted, the filtration is terminated, and the recovery bag connected to the downstream side of the filter via the blood circuit is cut along with the circuit at a point 30 to 40 cm downstream of the blood outlet of the filter. The red blood cell preparation was used as the recovery liquid.

The red blood cell preparation before filtration (hereinafter referred to as "pre-filtration liquid") and the volume of the recovered liquid, hematocrit, and white blood cell count were measured to determine the red blood cell recovery rate and leukocyte residual rate. Red blood cell recovery rate = {recovered solution volume x hematocrit (recovered solution)} / {pre-filter solution volume x hematocrit (pre-filtered solution)} Leukocyte residual rate = {white blood cell count (recovered solution)} / {pre-filter solution volume x leukocyte concentration (Pre-filtration liquid)} The volume of the pre-filtration liquid and the recovery liquid is 1.
The value was divided by 075 (representative specific gravity of red blood cell preparation). The white blood cell concentration in the pre-filtration liquid was measured by the following method.

Measurement of leukocyte concentration of pre-filtration solution: 10-fold diluted pre-filtration solution with Turk's solution was injected into a Berker Turk type hemocytometer (Elma, Japan), and large sections were divided into 4 sections using an optical microscope. The white blood cells present therein were counted, and this value was _designated as n _pre . White blood cell concentration = n _pre × (1/4) × 10 ⁵ cells / ml The number of white blood cells in the recovered liquid was measured by the extremely sensitive method described below.

5% Ficoll 400DL (Sigma Chemical Co., St. Louis, USA) in a bag containing the recovered liquid.
The EBSS solution (hereinafter referred to as Ficoll solution) was added while mixing the recovered solution with the same volume by shaking, and the recovery bag was fixed on the plasma separation stand and left standing for 40 minutes. After leaving still, the supernatant was gently collected so as not to disturb the sedimented red blood cell layer, and then the Ficoll solution was again added to the collection solution bag of the same volume as the previous time, and the same operation was repeated. The supernatant collected by the two operations is dispensed into four Corning 25350-250 centrifugal tubes (Corning Laboratory Science, New York, USA) and centrifuged at 840 xg for 15 minutes, taking care not to suck up the precipitate. Meanwhile, the supernatant was discarded with an aspirator. 200 ml of hemolyzed blood (1.145% ammonium oxalate physiological saline) in each centrifuge tube
The mixture was shaken to mix, immediately centrifuged at 468 × g for 10 minutes, and the supernatant was discarded with an aspirator while paying the same attention as above.

The four precipitates were collected in a 15 ml centrifuge tube, hemolyzed blood was added to bring the total volume to 15 ml, the mixture was allowed to stand at room temperature for 10 minutes, centrifuged at 468 × g for 10 minutes, and the precipitates were added. The supernatant was carefully discarded, leaving 5 ml. The solution containing the precipitate was thoroughly stirred to form a single cell suspension, and 50 μl of a fluorescent staining solution [69.9 mg / l acridine orange solution (Nacalai Tesque, Inc., Japan)] was added and further stirred. This solution was injected into 6 sheets of improved Neubauer hemacytometer (Reichert Co., Buffalo, USA), and white blood cells present in 108 large sections were counted using an epi-illumination fluorescence microscope (Nikon, Japan). did. White blood cells (recovered liquid) were calculated from the count value n _post by the following formula. White blood cell count (recovered solution) = n _post × (1/108) × 10 ⁴
X 0.55 x (1 / 0.55)

The underlined portion is the white blood cell concentration (cells / ml) in the liquid finally concentrated to 0.55 ml (hereinafter referred to as the concentrated liquid) from the recovered liquid using Ficoll liquid, and the volume of the concentrated liquid was 0. The white blood cell count is calculated by multiplying by 55 ml. The reason for further dividing by 0.55 is that the recovery rate when leukocytes are recovered using Ficoll solution is 55%. As a result, the white blood cell residual rate was 10 ^−4.5 , the pressure loss at the end of filtration was 75 mmHg, and the red blood cell recovery rate was 90.2%. The white blood cell removal rate of the second filter element of the main filter is 9
It was 7.6%. In addition, since the leukocyte removal rate of the second filter element is relatively high in leukocyte concentration after filtration by the second filter element, the above-mentioned "leukocyte concentration of the pre-filtration liquid before and after filtration by the second filter element is Determined by the method described in the section "Measurement".

Comparative Example 1. As the main filter, only a polyester melt-blown non-woven fabric having an average fiber diameter of 1.80 μm was used, and the packing density was 0.40.
An experiment was performed under the same conditions as in Example 1 except that the filling was performed so that the thickness was g / cm ³ and the thickness was 5.0 mm. The internal space volume of this filter was 30.0 ml. As a result of the experiment, the white blood cell residual rate was 10 ^−3.8 , the pressure loss at the end of filtration was 77 mmHg, and the red blood cell recovery rate was 90.3%.

Comparative Example 2. As the main filter, only a polyester melt blown nonwoven fabric having an average fiber diameter of 1.23 μm was used, and the packing density was 0.23.
An experiment was performed under the same conditions as in Example 1 except that the filling was performed so that the thickness was g / cm ³ and the thickness was 5.0 mm. The internal space volume of this filter was 32.2 ml. As a result of the experiment, the white blood cell residual rate was 10 ^−4.4 , the pressure loss at the end of filtration was 147 mmHg, and the red blood cell recovery rate was 90.1%.

Example 2. Prefilters with average fiber diameters of 32 μm and 13 μm
2 kinds of spunbonded non-woven fabrics with an average packing density of 0.30
g / cm ³ , a total thickness of 1.1 mm was filled in a container having an effective filtration area of 67 mm × 67 mm, and on the downstream side in the same container, as a second filter element of the main filter,
Average fiber diameter 1.75μm, average pore size 13.7μ
m polyester meltblown nonwoven fabric with a packing density of 0.
17 g / cm ³ , filling to a thickness of 0.8 mm,
Further downstream as the first filter element,
Average fiber diameter 1.23μm, average pore size 10.4μ
m polyester meltblown nonwoven fabric with a packing density of 0.
27 g / cm ³ and a thickness of 4.2 mm,
Created a leukocyte removal filter (A of the first filter)
The value is 0.22). The internal space volume of this filter is 32.3.
ml, effective filtration area is (6.7 cm) ² = 44.9 cm
^{Was 2} .

From 456 ml of whole blood prepared by adding 56 ml of CPD solution to 400 ml of blood, 200 ml of platelet-rich plasma was removed by centrifugation within 8 hours after blood collection, and stored at 4 ° C. for 3 days. The liquid (hematocrit 67%) was allowed to stand at room temperature (26 ° C) until it reached 25 ° C, and then filtered through the above-mentioned falter. To start the filtration, the filter was connected to the blood bag containing the red blood cell preparation through the blood circuit, and then the blood bag was pressurized to forcibly fill the filter with blood. Thus, after the blood is filled in the filter, the drop is 1.5m.
The filtration was started at. Filtration was completed when the red blood cell concentrated liquid in the blood bag disappeared and the blood flow substantially stopped. After the filtration was completed, the recovery bag connected to the downstream of the filter via the blood circuit was cut together with the circuit at a point 30 to 40 cm downstream of the blood outlet of the filter, and the red blood cell preparation in the circuit and the recovery bag was used as the recovery liquid. The red blood cell recovery rate and white blood cell residual rate were measured by the same methods as in Example 1.

As a result, the white blood cell residual rate was 10 ^−4.7 , the filtration time was 31 minutes, and the red blood cell recovery rate was 91.0%. The leukocyte removal rate of the second filter element of the main filter was 62.0%.

Example 3. Prefilters with average fiber diameters of 32 μm and 13 μm
2 kinds of spunbonded nonwoven fabrics with an average packing density of 0.4 g /
cm ³ , total thickness 0.7 mm, also Panelon PF86
0 (manufactured by Dynic Corporation, Japan, average fiber diameter 12 μ
m) and a spunlace nonwoven fabric having an average diameter of 4.1 μm, so as to have an average packing density of 0.30 g / cm ³ and a total thickness of 0.5 mm, an effective filtration area of 90 mm × 9.
It was filled in a 0 mm container, and on the downstream side in the same container, as the second filter element of the main filter, the average fiber diameter was 1.7.
A polyester melt-blown nonwoven fabric having a pore size of 5 μm and an average pore size of 14.0 μm was filled so as to have a packing density of 0.38 g / cm ³ and a thickness of 0.7 mm, and further downstream of the same, an average fiber diameter of 1. 23
A polyester melt-blown nonwoven fabric having a pore size of 1 μm and an average pore size of 10.5 μm was filled to a packing density of 0.38 g / cm ³ and a thickness of 2.5 mm to prepare a leukocyte removal filter (the A value of the first filter element was 0.1. 31).
The internal space volume of this filter was 52.0 ml, and the effective filtration area was (9.0 cm) ² = 81.0 cm ² .

Erythrocyte concentrate prepared by removing 200 ml of platelet-rich plasma by centrifugation within 8 hours after blood collection from 456 ml of whole blood prepared by adding 56 ml of CPD to 400 ml of blood and stored at 4 ° C. for 14 days (Hematocrit 67%) was allowed to stand at room temperature (26 ° C.) until it reached 25 ° C., then 2 units of the red blood cell concentrate was collected in a 600 ml blood bag and filtered through the above filter. Head 1.
An experiment was conducted in the same manner as in Example 2 except that filtration was performed at 2 m.

As a result, the white blood cell residual rate was 10 ^-4.2 , the filtration time was 54 minutes, and the red blood cell recovery rate was 89.4%. The leukocyte removal rate of the second filter element of the main filter was 81.8%.

Example 4. As pre-filter, average fiber diameter 32μm and 13μ
2 types of spunbonded non-woven fabrics with an average packing density of 0.4
7g / cm ³ , total thickness 0.6mm, and Panelon P
F869 (manufactured by Dynic Co., Ltd., Japan, average fiber diameter 12 μm) and spunlace nonwoven fabric with an average diameter of 4.1 μm are effective to have an average packing density of 0.375 g / cm ³ and a total thickness of 0.4 mm. Filtration area 67mm x 6
It was filled in a 7 mm container, and on the downstream side in the same container, as the second filter element of the main filter, the average fiber diameter was 1.6.
A polyester melt-blown nonwoven fabric having an average pore size of 8 μm and an average pore size of 13.3 μm was filled so as to have a packing density of 0.33 g / cm ³ and a thickness of 1.2 mm. .8
A polyester melt-blown non-woven fabric having a pore size of 9 μm and an average pore size of 8.1 μm was filled to have a filling density of 0.30 g / cm ³ and a thickness of 2.3 mm to prepare a leukocyte removal filter. The internal space volume of this filter is 24.3 m
1, effective filtration area is (6.7 cm) ² = 44.9 cm ^2.
Met.

A red blood cell concentrate prepared by removing 200 ml of platelet-rich plasma by centrifugation within 8 hours after blood collection from 456 ml of whole blood prepared by adding 56 ml of CPD to 400 ml of blood, and stored at 4 ° C. for 12 days. (Hematocrit 68%) was left at room temperature (26 ° C) until it reached 25 ° C, and then filtered through the above filter. Drop 1.2
An experiment was conducted in the same manner as in Example 2 except that filtration was performed with m.

As a result, the white blood cell residual rate was 10 ^-4.3 , the filtration time was 48 minutes, and the red blood cell recovery rate was 90.0%. The leukocyte removal rate of the second filter element of the main filter was 85.2%.

Example 5. As pre-filter, average fiber diameter 32μm and 13μ
The average packing density is 0.2
4 g / cm ³ and a total thickness of 2.2 mm were filled in a container having an effective filtration area of 47 mm × 47 mm, and an average fiber diameter of 1.80 μm was used as the second filter element of the main filter on the downstream side in the same container. Average pore size 12.
8 μm polyester meltblown non-woven fabric was packed so as to have a packing density of 0.20 g / cm ³ and a thickness of 2.0 mm, and further downstream thereof, similarly as the first filter element, an average fiber diameter of 1.23 μm and an average pore size of 10 ．
A 2 μm polyester meltblown non-woven fabric was filled to a packing density of 0.20 g / cm ³ and a thickness of 2.0 mm to prepare a leukocyte removal filter (A value of the first filter was 0.16). The internal volume of this filter is 1
5.8 ml, effective filtration area (4.7 cm) ² = 22.
It was 1 cm ² . 450 ml of blood and 63 ml of CP
Prepared by removing 243 ml of platelet-rich plasma from the 513 ml of whole blood prepared by adding D by centrifugation within 8 hours after blood collection, and after storing at 4 ° C for 10 days, physiological saline was added to make erythrocytes 360 ml. Formulation (Hematocrit 6
3%) was left at room temperature (26 ° C) until it reached 25 ° C, and then filtered through the above filter. An experiment was conducted in the same manner as in Example 2 except that the white blood cell count of the recovered liquid was determined by the following method.

Leukocyte concentration (recovered liquid): 100 μl of recovered liquid
After adding 200 μl of hemolyzed blood and 30 μl of the fluorescent staining solution to the mixture and stirring, this solution was injected into 1 to 3 sheets of improved Neubauer-type hemocytometer (Reichert Co., Buffalo, USA), and an epi-illumination fluorescence microscope (K.K. The number of white blood cells present in the large compartments 4-54 was counted using Nikon, Japan), and this value was designated as n _post '. White blood cell concentration (recovered solution) = n _post '× (1 / measurement section number)
× (1 / 3.3) × 10 ⁴ cells / ml White blood cell count = recovered liquid volume × white blood cell concentration (recovered liquid) As a result, the white blood cell residual rate was 10 ^−2.5 and the filtration time was 15.
At 2 minutes, the red blood cell recovery was 91.4%. The white blood cell removal rate of the second filter element of the main filter is 8
It was 4.5%.

Comparative Example 3. As the main filter, only a polyester melt-blown non-woven fabric having an average fiber diameter of 1.80 μm was used, and the packing density was 0.23.
An experiment was conducted under the same conditions as in Example 4 except that the filling was performed so that the thickness was g / cm ³ and the thickness was 4.0 mm. The internal space volume of this filter was 15.5 ml. As a result of the experiment, the residual leukocyte rate was 10 ^-1.9 , the filtration time was 16.4 minutes,
The red blood cell recovery was 92.0%.

Comparative Example 4. As the main filter, only a polyester melt-blown non-woven fabric having an average fiber diameter of 1.23 μm was used, and the packing density was 0.17.
An experiment was conducted under the same conditions as in Example 4 except that the filling was performed so that the thickness was g / cm ³ and the thickness was 4.0 mm. The internal space volume of this filter was 15.8 ml. As a result of the experiment, the residual leukocyte rate was 10 ^-2.4 , the filtration time was 24.3 minutes,
The red blood cell recovery was 91.5%.

Example 6. As a pre-filter, a spunbonded non-woven fabric having an average fiber diameter of 13 μm has an average packing density of 0.28 g / cm ³ , a thickness of 2.8 mm, and a spunlace nonwoven fabric having an average fiber diameter of 4.1 μm has an average packing density of 0.28 g / cm ^3. , Thickness 1.
6 mm, as the main filter, as the second filter element, a melt blown nonwoven fabric with an average fiber diameter of 1.23 μm, an average packing density of 0.20 g / cm ³ , (average pore size 10.2 μm), a thickness of 4.6 mm, Similarly, as one filter element, a melt-blown non-woven fabric having an average fiber diameter of 0.72 μm and an average packing density of 0.28 g / cm ³ ,
(Average pore size 9.6 μm, A value 0.39), thickness 3.0 mm, the above non-woven fabric effective filtration area 30 mm ×
A container of 30 mm = 9.0 cm ² was filled from the upstream side to the downstream side in the above order. On the other hand, a copolymer of 2-hydroxyethyl methacrylate and dimethylaminoethyl methacrylate in a molar ratio of 97: 3 (hereinafter referred to as H
(Abbreviated as M-3) was synthesized by usual solution radical polymerization. As the polymerization conditions, the total monomer concentration in ethanol was 1.0 mol / 1, and the polymerization reaction was carried out at 60 ° C. for 8 hours in the presence of azobisisobutyronitrile 1/200 mol / 1 as an initiator. The obtained HM-3 was dissolved in ethanol at 40 ° C to a concentration of 1.0%, passed through a container filled with the above non-woven fabric, and dried while sending dry nitrogen,
Further, the surface of the fibers of the non-woven fabric was coated with HM-3 by pulling for 4 hours under vacuum at 40 to 120 ° C. for sufficient drying to prepare a leukocyte removal filter for a platelet preparation. The internal space volume of this filter was 11.0 ml.

Platelet concentrate 1 obtained from the Japanese Red Cross Society
0 unit (stored for 4 days) was filtered through the above filter with a 1.2 m drop at room temperature. The filtration time was 28 minutes.
The platelet recovery rate and leukocyte residual rate were calculated by the following formulas. The platelet concentration before and after filtration and the white blood cell concentration before filtration were measured using an automatic hemocytometer (Symex MICROCELL-CO).
UNTER F-800, Toa Medical Electronics Co., Ltd.), and the white blood cell concentration after filtration is the cytospin method developed by Takahashi et al. (Journal of Japanese Society of Transfusion, Volume 35, No. 5,
497-503, 1989). The volume before and after filtration was the value obtained by dividing the weight before and after filtration by the specific gravity of 1.025. As a result, the platelet recovery rate was 89.6%,
The white blood cell residual rate was 10 ^-4.6 . The white blood cell removal rate [{1- (white blood cell residual rate)} × 100] of the second filter element of the main filter was 87.3%.

[0063]

INDUSTRIAL APPLICABILITY The leukocyte-removing filter and leukocyte-removing method of the present invention have a small pressure loss during filtration and a leukocyte residual ratio of 10 ⁻⁴ without causing an extreme decrease in the flow rate associated with blood treatment.
It is possible to achieve a high leukocyte-removing ability and a high recovery rate of 85 to 90% of red blood cells or platelets, which are clinically extremely significant as follows. Further, when the present invention is applied to a popular leukocyte removal filter having a leukocyte residual rate of about 10 ^-2 to 10 ^-3 , a smaller filter with a pressure loss equivalent to that of the conventional one or an internal volume equivalent to that of the conventional one is more effective. It is possible to provide a filter with low pressure loss.

Claims (6)

[Claims] 1. A leukocyte-removing filter comprising a plurality of filter elements having different average fiber diameters, which has a first filter element having an average fiber diameter of 0.3 to 1.6 μm, and is contained in blood to be treated. A second filter element, which has a larger average fiber diameter than the first filter element and removes 60% or more of the white blood cells of the above, is arranged upstream of the blood to be treated than the first filter element. A white blood cell removal filter. 2. The second filter element comprises a filter element having an average fiber diameter of 0.8 to 3.0 μm and 1.2 times or more of the first filter element, The leukocyte removal filter according to claim 1. 3. The leukocyte depletion filter of claim 1, wherein the average pore size of the first filter element is 2-18 μm. 4. The leukocyte depletion filter according to claim 1, wherein the second filter element comprises a filter element having an average pore size of 4 to 25 μm. 5. After removing 60% or more of leukocytes in the blood to be treated, leukocytes are further removed by a leukocyte removal filter having a first filter element having an average fiber diameter of 0.3 to 1.6 μm. A characteristic leukocyte removal method. 6. A second filter element having an average fiber diameter of 0.8 to 3.0 μm and 1.2 times or more that of the first filter element when removing 60% or more of white blood cells. Leukocyte removal method.