JP3419831B2 - Aggregate removal filter in blood and filter device for blood treatment - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a filter for removing aggregates in blood and a blood treatment filter device. More specifically, the present invention relates to a filter for removing aggregates contained in blood products for transfusion and a filter device for removing aggregates and white blood cells contained in the blood products.

[0002]

2. Description of the Related Art In recent years, in transfusion, so-called leukocyte-removing transfusion, in which leukocytes contained in blood products are removed and then transfusion has been widely performed. This is because the white blood cells contained in blood products cause various side effects such as non-hemolytic fever reaction and platelet transfusion intolerance. The method of removing leukocytes from blood products is a method by centrifugation,
There is a method of using a leukocyte removal filter device made of fibers or a porous material, but the latter is superior in terms of high leukocyte removal rate and ease of use, and is widely used.

Many leukocyte removal filter devices are composed of a plurality of types of filter materials, and a coarse filter material (hereinafter referred to as a prefilter) for removing aggregates of blood products is provided in an upstream portion near the blood inlet. Call)
However, a fine filter material (hereinafter referred to as a main filter) for removing white blood cells is arranged on the downstream side on the outlet side. Aggregates are formed by agglutination of red blood cells, white blood cells, platelets, fibrin, fibrinogen, other denatured proteins, fat globules, etc. Small ones are about the same size as white blood cells, and large ones exceed 1 mm. There are even such things, and it is rich in stickiness. In addition, the number of aggregates increases with time as the blood product is stored, and the size increases. Therefore, if the blood product is treated only with the main filter without using the pre-filter, the main filter is clogged with the aggregates, and the expected flow rate cannot be maintained. This tendency is stronger for blood products that have been stored for more days.

A typical prefilter that has been used in a leukocyte removal filter device for blood transfusion has been disclosed in Japanese Patent Laid-Open No. Sho 60/1985.
-203267, Japanese Patent Laid-Open No. 1-236064, Publication No. 3-
It is disclosed in 502094 and the like. Japanese Patent Laid-Open No. 60-203267 discloses that "fiber diameter is 3 to 60 .mu.m.
, A modified blood component removal filter containing at least one fiber lump having a bulk density of 0.05 to 0.5 g / cm ³ "is disclosed as a representative leukocyte removal filter device widely distributed in the market. It is used as a pre-filter. Japanese Unexamined Patent Publication No. 1-236064 discloses "Average fiber diameter X.
And a mean inter-fiber spacing Y, XY, which is slightly larger than white blood cells having a size of 7 or more and less than 50, and a relatively small micro-aggregate, and a large micro-aggregate having an XY of 50 or more. A "prefilter for supplementing substances" is disclosed and is used in a typical leukocyte removal filter device which is also widely distributed in the market. Japanese Patent Laid-Open No. 3-502094 discloses a gel removing pre-filter made of a non-woven fabric having a needle punching treatment and having an appearance of a combination of coils having random diameters, and a pore size smaller than the pre-filter. A prefilter for removing microaggregates, which is composed of a combination of melt blown webs of more layers, is disclosed and is used in a typical leukocyte removal filter device which is also widely distributed in the market.

These typical leukocyte depletion filter devices can process relatively old blood products which have been stored for a long time in many cases. When blood products that are presumed to contain relatively large amounts of large aggregates, such as blood products prepared with insufficient anticoagulant and blood mixing, are frequently clogged and the flow rate is extremely high. There was a problem that it decreased to.

Further, Japanese Patent Application Laid-Open No. 48-66285 discloses an aggregate removal filter device for removing aggregates from blood products for transfusion and allowing red blood cells and white blood cells to pass through. Three sheets, a first sheet having holes having a size of 800 to 4000 μm, a second sheet having holes having a size of 20 to 50 μm, and a third sheet having holes having a size of 10 to 30 μm, are provided downstream. They are arranged so that the degree of fineness increases in order as they go. It is considered that the aggregate removal filter device is functionally equivalent to the pre-filter part in the leukocyte removal filter device. However, when the technique is applied to the leukocyte removal filter device, whether clogging can be effectively prevented or not can be determined. There is no knowledge about.

[0007]

As described above, the conventional leukocyte-removing filter device has a particularly old blood product with an expiring expiration date, or an anticoagulant mixed with blood after blood collection is insufficient. There is a problem that it often clogs when processing prepared blood products etc.,
The capacity of the prefilter was insufficient. An object of the present invention is to treat these bloods having a particularly strong tendency to be clogged while maintaining a good flow rate, and a filter for removing aggregates contained in blood products for transfusion, and a built-in filter. To provide a filter device for removing aggregates and leukocytes contained in a blood product. More specifically, from a blood product having a particularly strong tendency to be clogged as described above, a filter for blood treatment capable of effectively removing aggregates without clogging by itself.
And by incorporating the filter on the upstream side of the leukocyte removal filter device, it is possible to prevent clogging of the pre-filter disposed on the downstream side of the filter and to reduce the processing flow rate over time when performing blood processing by gravity. It is an object of the present invention to provide a blood processing filter device capable of reducing the inconvenience caused by clogging of agglomerates such as increase in pressure loss with time when performing blood processing using a pump.

When the leukocyte removal filter device is clogged, a general countermeasure is to dispose a drip tube containing a screen filter having a pore diameter of about 200 to 400 μm on the upstream side of the filter. By removing relatively large aggregates with the screen filter,
It is possible to reduce clogging of the leukocyte removal filter device. However, since the area of the screen filter that can be incorporated in the drip tube is relatively small, there is a problem that the screen filter is clogged especially when treating blood having a strong clogging tendency. In addition, since blood remaining in the drip tube after the filtration is discarded together with the leukocyte removal filter device, there is a problem that blood loss increases.

Therefore, the present inventors tried to solve these problems by incorporating the screen filter in the leukocyte removal filter device to expand the area of the screen filter and eliminate the drip tube. In particular, with this method, the effect of reducing clogging of the leukocyte removal filter device was hardly obtained. Furthermore, the same experiment was carried out by incorporating various screen filters having larger pore diameters, but only a slight improvement was observed and an insufficient effect could be obtained.

[0010]

[Means for Solving the Problems] Therefore, as a result of re-investigating what characteristics are preferable as a pre-filter incorporated in a leukocyte removal filter device, as a result, a particularly old blood product with a near expiration date and an anti-after When treating blood products such as blood products that have been prepared while the coagulant and blood are not sufficiently mixed, especially when treating blood products that have a strong tendency to be clogged, a prefilter that has only a single pore size or a pore size distribution The narrow pre-filter does not function effectively, and has at least two kinds of pores of different sizes in the same sheet, each pore has an optimum average pore diameter range, and the open area ratio is a certain level or more. It was found that good results were obtained when a filter material was used, and the present invention was completed.

That is, the gist of the present invention is as follows. Within the same sheet, there are at least two types of pore groups, each having a pore size A of 500 μm or more and a pore group B having an individual pore size of 150 μm or more and less than 500 μm, and the average pore size of the pore group A is 600 to 1500 μm. Range, the average pore diameter of the pore group B is in the range of 200 to 450 μm, and the open area ratio is 40% or more, a filter for removing aggregates in blood. Individual pore size is 500μm in the same sheet
The above hole group A and individual hole diameters are 150 μm or more and 500 μm
Having at least two types of pore groups with a pore group B of less than, the average pore diameter of the pore group A is in the range of 600 to 1500 μm, the average pore diameter of the pore group B is in the range of 200 to 450 μm, and the air permeability is 360 cc. / Cm ² · sec or more, a filter for removing aggregates in blood. Within the same sheet, each hole group A having an individual hole diameter of 500 μm or more and each individual hole diameter is 1
At least 2 with the group of pores B of 50 μm or more and less than 500 μm
A filter for removing aggregates in blood, which has a group of pores and has an opening ratio of 40% or more and an air permeability of 360 cc / cm ² · sec or more. A blood processing filter device for reducing aggregates and leukocytes in blood, which has an inlet and an outlet for blood, and which is separated by a plurality of types of filters.
At least one of the filters has a group of pores A each having a pore size of 500 μm or more and an individual pore size of 150 in the same sheet.
Pore group B having at least two types of pore groups B having a size of from .mu.m to less than 500 .mu.m, and the average pore diameter of the group of holes A is 600 to 1500 .mu.
m is a filter for removing aggregates in blood, in which the average pore diameter of the pore group B is in the range of 200 to 450 μm, and the opening ratio is 40% or more, and the filter is substantially on the most inlet side. A blood processing filter device characterized by being arranged. A blood processing filter device for reducing aggregates and leukocytes in blood, which has an inlet and an outlet for blood, and is separated from the inlet and the outlet by a plurality of types of filters, at least the filter being provided. Each has a hole size of 500μ in the same sheet .
Pore group A of m or more and individual pore size of 150 μm or more and 500 μm
Pore group B having at least two kinds of pore group B and pore group B of less than m, the average pore diameter of pore group A being 600 to 1500 μm, pore group B
Is a filter for removing aggregates in blood having an average pore size in the range of 200 to 450 μm and an air permeability of 360 cc / cm ² · sec or more, and the filter is substantially disposed at the inlet side. A blood processing filter device characterized by the above. A blood processing filter device for reducing aggregates and leukocytes in blood, which has an inlet and an outlet for blood, and is separated from the inlet and the outlet by a plurality of types of filters, at least the filter being provided. One has 500 individual holes in the same sheet
Pore group A of μm or more and individual pore size of 150 μm or more 500
having at least two types of pore groups with a pore group B of less than μm,
Moreover, the porosity is 40% or more, and the air permeability is 360 cc / cm ^2.
A blood processing filter device, which is a filter for removing aggregates in blood having a duration of 2 seconds or more, and the filter is substantially disposed at the inlet side.

In the present invention, the pores, pore diameter, pore group A, pore group B, pore group C, average pore diameter, open area ratio, and air permeability are defined as follows. The term "pore" refers to a space existing in the filter material, excluding any space that is clearly recognized as an independent space whose periphery is closed, and the pore diameter is a surface perpendicular to the thickness direction of the filter material ( Hereinafter, the diameter of a hole whose cross-section appears in (a surface), when the cross-sectional area of the hole on the surface is converted into a perfect circle. The group of holes A is a concept that the holes whose pore size is recognized to be 500 μm or more on the surface are regarded as belonging to one group and are called, and similarly, the pore group B is recognized that the pore size is 150 μm or more and less than 500 μm on the surface. The hole group C has a hole diameter of 50 μm or more on the surface.
This is a concept in which pores recognized as smaller than 50 μm are regarded as belonging to one group and are called. The average pore diameter in the present invention is obtained for each of the hole group A, the hole group B, and the hole group C.
That is, the average pore diameter of the pore group A is 50 on the surface.
It is the arithmetic mean of the hole diameters of the hole cross sections recognized to be 0 μm or more, and the average hole diameter of the hole group B is 150 μm on the surface.
It is the arithmetic mean of the pore diameters of the cross section of pores recognized to be m or more and less than 500 μm, and the average pore diameter of the pore group C is the arithmetic mean of the pore diameters of the pore cross sections recognized to be 50 μm to less than 150 μm on the surface. The porosity refers to the ratio of the area of the hole cross section on the surface to the total area of the hole cross section and the area other than the hole cross section. Further, the air permeability is a fabric air permeability tester (AP-360 type, manufactured by Daiei Kagaku Seiki Co., Ltd.,
The value measured in Kyoto City, Japan) is converted into the value per 1 mm of the thickness of the filter material.

The filter material of the present invention always has the above-mentioned pore group A and pore group B, and the pore group A has an average pore diameter of 600.
To 1500 μm, the average pore size of the pore group B is 200 to 4
It is necessary to satisfy two or more conditions out of the three conditions of being in the range of 50 μm, having an opening ratio of 40% or more, and having an air permeability of 360 cc / cm ² · sec or more. . When only one of the hole group A and the hole group B is provided, the effect of reducing clogging is low regardless of the size of the hole diameter and the opening ratio. When the open area ratio is less than 40%, the effect of reducing clogging is low regardless of the size of the hole diameter. The air permeability is a physical property value that changes depending on both the pore size distribution and the open area ratio, and a preferable filter can be defined by a combination with either the pore size distribution or the open area ratio.

In the filter device of the present invention, the filter of the present invention is arranged at a portion closest to the blood inlet, or a filter having an average pore diameter of less than 600 μm is provided at a portion closer to the blood inlet than the filter, It is necessary that no filter with a lower air permeability than the filter of the invention is arranged. If a filter having an average pore size of less than 600 μm or a filter having a low air permeability is disposed closer to the blood inlet side than the filter of the present invention, clogging occurs at that portion, and the significance of arranging the filter of the present invention is lost. Be seen.

The filter of the present invention is not limited to a leukocyte removal filter device for blood transfusion, but also an agglutination removal filter device for removing agglutinates of blood products for blood transfusion, a leukocyte removal filter device for extracorporeal circulation treatment, It can also be used as a filter for an aggregate removal filter device for removing aggregates from blood in the extracorporeal circulation.

[0016]

EXAMPLES The present invention will be described in more detail with reference to examples.

[0017]

Example 1 Three groups of pores A having an average pore diameter of 850 μm, a pore group B having an average pore diameter of 290 μm, and a pore group C having an average pore diameter of 110 μm were used, and the open area ratio was 48% and the air permeability was 48%. 420
A commercially available leukocyte removal filter device (Sepacell R-500 (II), Asahi Medical Co., Ltd., Tokyo, Japan) was used as a filter for removing aggregates having a cc / cm ² · sec and a thickness of 0.25 mm.
(Japan), and a new leukocyte removal filter device was created. A blood circuit without a drip tube is connected to the upstream side of this device, and the red blood cell concentrated liquid (Hct) that has been stored in the refrigerator for 48 days after blood collection from the circuit and is warmed to room temperature immediately before processing (Hct) .70%)
Was passed at a constant flow rate of 2 ml / min, and the pressure loss before and after passing through the device was measured. This experiment was conducted as a so-called accelerated test by intentionally storing the concentrated red blood cell liquid having an expiration date of 21 days for 48 days to grow an aggregate. As a result, the pressure loss gradually increased with the lapse of time, but it was 80 mmHg 60 minutes later, 200 mmHg 90 minutes later, and 300 mmH 110 minutes after the red blood cell concentrate began to emerge from the blood outlet of the leukocyte removal filter device.
220 ml of filtered red blood cell concentrate could be collected until g was reached.

[0018]

[Comparative Example 1] A commercially available leukocyte removal filter device (Sepacell R-500 (II), Asahi Medical Co., Ltd., Tokyo, Japan)
The experiment was performed under the same conditions as in Example 1 except that (Japan) was used as it was. The pressure loss increases rapidly with the passage of time, 170 mmHg after 20 minutes and 320 mm after 40 minutes.
The experiment was stopped at this point when Hg was reached.

[0019]

Example 2 The same aggregate removal filter as in Example 1 was replaced with a commercially available leukocyte removal filter device (Sepacell R-5).
00 (III), Asahi Medical Co., Ltd., Tokyo, Japan)
A new leukocyte removal filter device was prepared by arranging the filter device on the most upstream side. Blood was collected at a height of 1.0 m for 48 days after blood collection in a refrigerator, diluted with physiological saline just before the treatment, and warmed to room temperature to concentrate red blood cells (Hct. 48).
%), The filter device at a height of 0.8 m, and the red blood cell collection bag at a position of 0 m,
The blood bag containing the concentrated red blood cell liquid before filtration and the filter device, and the filter device and the red blood cell recovery bag are connected by a blood circuit having an inner diameter of 3.3 mm, respectively.
The red blood cell concentrate was filtered using gravity. The flow velocity gradually decreased with the passage of time, but by the time 35 minutes later,
It was possible to collect 1 blood. The flow rate immediately after the start of filtration is 28 ml / min, and the flow rate at the time of collecting 500 ml is
It was 6.8 ml / min.

[0020]

Comparative Example 2 An experiment was carried out under the same conditions as in Example 2 except that a commercially available leukocyte removal filter device (Sepacell R-500 (III), Asahi Medical Co., Ltd., Tokyo, Japan) was used as it was. The flow rate rapidly decreased with the lapse of time, and it took 162 minutes to collect 500 ml. The flow rate immediately after the start of filtration was 29 ml / min, and the flow rate at the time of collecting 500 ml was 0.9 ml / min.

[0021]

The aggregate removal filter of the present invention has at least two kinds of pore groups having different pore sizes and has a specific open ratio or a specific air permeability, and therefore contains a large amount of aggregates. Aggregates can be effectively removed from blood products without clogging themselves. In the case of performing the blood treatment by gravity, the blood treatment filter device of the present invention in which the filter of the present invention is incorporated in the blood inlet side prevents clogging of the pre-filter arranged downstream of the filter of the present invention. It is possible to significantly reduce the inconvenience caused by clogging of aggregates, such as a decrease in the processing flow rate with time, an increase in pressure loss when performing blood processing using a pump, and the like.

─────────────────────────────────────────────────── ─── Continuation of front page (56) Reference JP-A-58-180425 (JP, A) JP-A-56-31737 (JP, A) JP-A-54-66589 (JP, A) JP-A-58- 94863 (JP, A) JP-A 4-212373 (JP, A) JP-A 60-203267 (JP, A) JP-A 1-236064 (JP, A) Actual development S61-155012 (JP, U) Tokuhyo Hira 6-510455 (JP, A) Tokuhyo Hira 3-502094 (JP, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) A61M 5/165

Claims (6)

(57) [Claims] 1. The individual pore size is 500 μm in the same sheet.
The above hole group A and individual hole diameters are 150 μm or more and 500 μm
Having at least two types of pore groups with pore groups B below, the average pore diameter of the pore groups A is in the range of 600 to 1500 μm, the average pore diameter of the pore groups B is in the range of 200 to 450 μm, and the open area ratio is A filter for removing aggregates in blood, which is 40% or more. 2. Individual pore size within the same sheet is 500 μm.
The above hole group A and individual hole diameters are 150 μm or more and 500 μm
Having at least two types of pore groups with a pore group B of less than, the average pore diameter of the pore group A is in the range of 600 to 1500 μm, the average pore diameter of the pore group B is in the range of 200 to 450 μm, and the air permeability is 360 cc. / Cm ² · sec or more, a filter for removing aggregates in blood. 3. The individual pore size is 500 μm in the same sheet.
The above hole group A and individual hole diameters are 150 μm or more and 500 μm
Having a hole group B of at least 2 and a hole ratio of 40% or more and an air permeability of 360 cc / cm ² ·
A filter for removing agglomerates in blood, which is characterized in that it is more than a second. 4. A blood processing filter device for reducing aggregates and white blood cells in blood, which has an inlet and an outlet for blood, and the inlet and the outlet are separated by a plurality of types of filters. At least one of the filters has at least two kinds of pore groups in the same sheet, a pore group A having an individual pore diameter of 500 μm or more and a pore group B having an individual pore diameter of 150 μm or more and less than 500 μm, and the pore group A
Is a filter for removing aggregates in blood having an average pore size of 600 to 1500 μm, an average pore size of the pore group B in the range of 200 to 450 μm, and a porosity of 40% or more, and the filter is substantially The filter device for blood processing, which is characterized in that it is disposed on the most inlet side. 5. A blood processing filter device for reducing aggregates and white blood cells in blood, which has an inlet and an outlet for blood, and the inlet and the outlet are separated by a plurality of types of filters. At least one of the filters has at least two kinds of pore groups in the same sheet, a pore group A having an individual pore diameter of 500 μm or more and a pore group B having an individual pore diameter of 150 μm or more and less than 500 μm, and the pore group A
Has an average pore diameter of 600 to 1500 μm, an average pore diameter of the pore group B is in the range of 200 to 450 μm, and an air permeability of 360 cc / cm ² · sec or more. A filter device for blood treatment, wherein the filter is disposed substantially at the inlet side. 6. A blood processing filter device for reducing aggregates and white blood cells in blood, which has an inlet and an outlet for blood, and the inlet and the outlet are separated by a plurality of types of filters. , At least one of the filters has at least two kinds of pore groups in the same sheet, a pore group A having an individual pore diameter of 500 μm or more and a pore group B having an individual pore diameter of 150 μm or more and less than 500 μm, and the open area ratio Is a filter for removing aggregates in blood having an air permeability of 40% or more and an air permeability of 360 cc / cm ² · sec or more, and the filter is disposed substantially at the inlet side for blood treatment. Filter device.