JP2017086299A - Leukocyte removal filter and designing method of leukocyte removal filter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a leukocyte removal filter capable of filtering blood effectively using a whole filter surface without lowering a flow velocity in the thickness direction regardless of where the filter material is positioned in flow direction and width direction.SOLUTION: A leukocyte removal filter A is disclosed, wherein a height (t1) of an upstream-side passage forming rib 2A is 0.5 mm or more, the upstream-side passage forming rib provided on an inner face of an upstream-side container body 2 forming an upstream-side passage of a nonwoven or porous filter material; the height (t2) of a downstream-side passage forming rib 3A is 0.5 mm or more, the downstream-side passage forming rib provided on an inner face of a downstream-side container body 3 forming a downstream-side passage of the filter material; and (t1+t2) is from 1 mm and less than 5 mm.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a leukocyte removal filter that efficiently removes leukocytes that remain in a blood product and cause various non-hemolytic side effects, and more particularly to a leukocyte removal filter in which a container for containing a filter material is hard.

Blood products for blood transfusion are preparations in which leukocytes are removed in advance before storage for the purpose of reducing blood transfusion side effects such as fever reaction and infection caused by leukocytes.
For the purpose of preparing a blood product for transfusion, three methods are required as a method for removing leukocytes from blood, that is low cost, that it is disposable from the viewpoint of safety, and that the operation is simple. Therefore, a leukocyte removal filter made of a nonwoven fabric or a porous filter material is used. The leukocyte removal filter includes a container main body that accommodates the filter material, an upstream container main body that forms a flow path on the upstream side of the filter material, an inflow port that communicates with a space in the upstream container, and the filter A leukocyte removal filter having a simple configuration comprising a downstream container body that forms a flow path on the downstream side of a material and an outlet that communicates with the space in the downstream container is widely used (for example, patents) References 1, 2, 3, 4).
The leukocyte removal filter has a structure in which the inflow port and the blood bag are connected by a tube, and the outflow port and the blood collection bag are connected by a tube to form a leukocyte removal system. Is introduced into the leukocyte removal filter, and the number of leukocytes contained in the blood collection bag is reduced to 1 × 10 ⁶ or less, for example, by filtration with a filter material.
Here, as a container for storing the filter material in the leukocyte removal filter, a flexible soft container (for example, FIG. 1 and FIG. 2 of Patent Document 2, FIG. 1 of Patent Document 3, and FIG. 2 of Patent Document 4). And a rigid container that does not have flexibility (for example, see FIG. 5 of Patent Document 1 and FIG. 11 of Patent Document 2).

JP-A-1-320064 JP-A-7-267871 JP 2005-296475 A JP 2011-072817 A

In the conventional leukocyte removal filter, if the container for storing the filter material is soft, the following disadvantages (1), (2), (3), and (4) are present as compared with the case where the container is hard.
(1) Manufacturing cost increases.
Since the soft sheet and the tube serving as the blood inlet / outlet must be produced in separate steps, and the step of attaching the tube to the soft sheet is required, the manufacturing cost increases.
(2) The filtration time is long.
Since it is difficult to install the flow path forming rib on the inner surface of the container, the filtration time becomes longer.
(3) A bulge prevention band is required.
Since the time taken for the container that has expanded due to the inflow of blood to contract during filtration is long and the blood that remains in the container and cannot be recovered increases, a swell-prevention band as in Patent Document 3 is required.
(4) Large size.
Since it is necessary to increase the size of the width of joining the outer periphery of the soft sheet on the front and back, the size increases. Moreover, in the case of the same size, the performance deteriorates.

In the conventional leukocyte removal filter, if the container for storing the filter material is hard, there is no such disadvantage, and this is an advantage over the soft container. That is, in the leukocyte removal filter in which the container for storing the filter material is hard, the tube serving as the blood inlet and outlet and the rib for forming the flow path can be integrally formed in the container by injection molding, so that the manufacturing cost can be reduced. At the same time, the filtration time can be shortened. Further, since the container does not expand, a swell prevention band is not required, and the area of the joint portion on the outer periphery of the pair of container main bodies (housings) can be reduced, thereby reducing the size.
However, the inventor of the present application made a leukocyte removal filter model in which the container for containing the filter material is hard and conducted a flow analysis. became.

  Therefore, in view of the flow analysis result, the problem to be solved by the present invention is to provide a leukocyte removal filter and a leukocyte removal filter design method that can effectively filter the entire surface of the filter.

  As a result of intensive studies to solve the above problems, the present inventors have completed the present invention.

That is, the gist of the present invention is as follows.
[1] It comprises a non-woven fabric or porous filter material, an upstream container body that forms a flow path on the upstream side of the filter material, and a downstream container body that forms a flow path on the downstream side of the filter material. A container containing the filter material, an inlet communicating with the upstream container body, an outlet communicating with the downstream container body, and an upstream channel provided on the inner surface of the upstream container body A leukocyte removal filter comprising a forming rib and a downstream flow path forming rib provided on the inner surface of the downstream container body,
The height (t1) of the upstream flow path forming rib and the height (t2) of the downstream flow path forming rib are 0.5 mm or more (t1 ≧ 0.5 mm, t2 ≧ 0.5 mm). The sum (t1 + t2) of the height (t1) of the upstream flow path forming rib and the height (t2) of the downstream flow path forming rib is 1 mm or more and less than 5 mm (1 mm ≦ (t1 + t2) < 5 mm) Leukocyte removal filter.
[2] The leukocyte removal filter according to [1], wherein the downstream container body is provided with a discharge channel.
[3] A nonwoven fabric or porous filter material, an upstream container body that forms a flow path on the upstream side of the filter material, and a downstream container body that forms a flow path on the downstream side of the filter material, A container containing the filter material, an inlet communicating with the upstream container body, an outlet communicating with the downstream container body, and an upstream channel provided on the inner surface of the upstream container body A leukocyte removal filter design method comprising: a forming rib; and a downstream flow path forming rib provided on the inner surface of the downstream container body,
The height (t1) of the upstream flow path forming rib and the height (t2) of the downstream flow path forming rib are set to 0.5 mm or more (t1 ≧ 0.5 mm, t2 ≧ 0.5 mm). The sum (t1 + t2) of the height (t1) of the upstream flow path forming rib and the height (t2) of the downstream flow path forming rib is 1 mm or more and less than 5 mm (1 mm ≦ (t1 + t2) < 5 mm) A leukocyte removal filter design method.
[4] The design method according to [3], wherein the downstream container body is further designed to include an outlet channel.

  According to the leukocyte removal filter and the leukocyte removal filter design method according to the present invention, the flow velocity in the thickness direction is uniform without decreasing regardless of the position in the flow direction and width direction of the filter material. Can be used effectively to filter blood. In addition, by providing the outlet channel in the downstream container body, the flow rate to the outlet side can be increased and the filtration time can be shortened.

(A) is a front view of the leukocyte removal filter which concerns on embodiment of this invention, (b) is a back view similarly. Similarly, it is a right side view. (A) is an arrow XX sectional view of Drawing 1 (a), and (b) is an important section expanded sectional view similarly. The modification (hexagonal shape) of the shape of a leukocyte removal filter is shown, (a) is a front view, (b) is a rear view. It is a front view which shows the modification (polygonal shape) of the shape of a leukocyte removal filter, (a) is a triangular shape, (b) is a square shape, (c) is a pentagonal shape. It is a front view which shows the modification (polygonal shape) of the shape of a leukocyte removal filter, (a) is a heptagon shape, (b) is an octagon shape, (c) is a nine-sided shape, (d) is a decagonal shape. is there. The modification (circle shape) of the shape of a leukocyte removal filter is shown, (a) is a front view, (b) is a rear view.

Next, embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the present invention is not limited to the embodiments shown in the accompanying drawings, and includes all the embodiments that satisfy the requirements described in the claims. It is a waste.
In the present specification, the front view is a view of the leukocyte removal filter in the use state as it faces the upstream container body.

FIG. 1A is a front view, FIG. 1B is a rear view, FIG. 2 is a right side view, FIG. 3A is a cross-sectional view taken along the line XX, and FIG. As shown in the enlarged cross-sectional view, the leukocyte removal filter according to the embodiment of the present invention has a rectangular flat appearance, and includes a filter material F, a hard container 1 containing the filter material F, and a hard container 1. A flow that communicates with the space in the flat rigid upstream container body 2 that opens, communicates with the inlet 4 that opens upward, and the space within the flat rigid downstream container body 3 that forms the rigid container 1, and opens downward. An outlet 5 is provided.
Further, an upstream flow path forming rib 2A is provided on the inner surface of the upstream container body 2, and a downstream flow path forming rib 3A is provided on the inner surface of the downstream container body 3, as shown in FIG. The height t1 of the upstream flow path forming rib 2A and the height t2 of the downstream flow path forming rib 3A are 0.5 mm or more (t1 ≧ 0.5 mm, t2 ≧ 0.5 mm), respectively. (T1 + t2) is 1 mm or more and less than 5 mm (1 mm ≦ (t1 + t2) <5 mm).
The outer peripheral side rib 2B provided on the outer peripheral side of the inner surface of the upstream container body 2 and the outer peripheral side rib 3B provided on the outer peripheral side of the inner surface of the downstream container body 3 shown in FIG. This is to prevent a short pass of blood.
Furthermore, an outlet channel 6 is formed on the inner surface of the downstream container body 3 to collect the filtered blood and increase the flow rate to the outlet side, extending in the vertical direction and connected to the outlet 5.

Here, the upstream container body 2 forms a flow path on the upstream side of the filter material F, and the downstream container body 3 forms a flow path on the downstream side of the filter material F. The downstream container body 3 is made of a transparent synthetic resin such as polycarbonate (PC), polypropylene (PP), polyethylene (PE), polystyrene (PS), styrene-butadiene copolymer, ABS resin, acrylic resin, polyester, nylon, and the like. Yes, the rigid container 1 that accommodates the filter material F is formed in a state of being joined by ultrasonic welding or the like.
Further, the filter material F is a nonwoven fabric or a porous body, and is disposed on the upstream side, and is disposed on the downstream side, the prefilter material (low-density filter portion) F1 for capturing and removing microaggregates. The main filter material (high-density filter part) F2 for capturing and removing leukocytes.

In the leukocyte removal filter A (hard container 1) according to the present invention, in order to reduce the flow resistance parallel to the layers in the first layer and the fourth layer and increase the flow diffusion effect, The sum (t1 + t2 = t) of the length t1 and the height t2 of the downstream flow path forming rib 3A is set to 1.0 mm or more (t ≧ 1.0 mm), and the height t1 of the upstream flow path forming rib 2A The height t2 of the downstream side flow path forming rib 3A is 0.5 mm or more (t1 ≧ 0.5 mm, t2 ≧ 0.5 mm).
In the present invention, t1 is not particularly limited as long as it is 0.5 mm or more, but may be 0.6 mm or more, 0.8 mm or more, 1.0 mm or more, 2.4 mm or less, 2.2 mm or less, 2 It may be 0.0 mm or less.
In the present invention, t2 is not particularly limited as long as it is 0.5 mm or more, but may be 0.8 mm or more, 1.0 mm or more, 1.2 mm or more, 2.4 mm or less, 2.2 mm or less, 2 It may be 0.0 mm or less.
In the present invention, t (= t1 + t2) is not particularly limited as long as it is 1.0 mm or more, but may be 1.2 mm or more, 1.4 mm or more, 1.6 mm or more, 1.8 mm or more, 2.0 mm or more. Also, it may be 4.8 mm or less, 4.6 mm or less, 4.4 mm or less, 4.2 mm or less, 4.0 mm or less.
Here, for example, when t = (t1 + t2) = 1.4 mm, t1 = 0.6 mm, t2 = 0.8 mm, or t1 = 0.8 mm, t2 = 0.6 mm, etc., and t1 = t2 It does not have to be.

In the above description, the case where the hard container 1 has a rectangular shape has been shown, but the hard container 1 may have a hexagonal shape as shown in FIG. 4 or a triangular shape as shown in FIG. 5 (b), pentagonal shape shown in FIG. 5 (c), heptagonal shape shown in FIG. 6 (a), octagonal shape shown in FIG. 6 (b), and nine shapes shown in FIG. 6 (c). It may be a polygonal shape such as a square shape, a decagonal shape shown in FIG. 6D, or the polygonal shape deformed vertically or horizontally.
Moreover, the circular shape as shown in FIG. 7 may be sufficient as the hard container 1, and a vertically long or horizontally long elliptical shape may be sufficient as it.

  Next, experimental examples (examples and comparative examples) performed by changing the height t1 of the upstream flow path forming rib 2A and the height t2 of the downstream flow path forming rib 3A will be described.

(Synthesis example)
Add 2-hydroxyethyl methacrylate (hereinafter abbreviated as HEMA) 0.95 mol / L ethanol solution and 2-diethylaminoethyl methacrylate (hereinafter abbreviated as DE) 0.05 mol / L ethanol solution to a three-necked flask equipped with a condenser. The volume was 250 mL.
As a polymerization initiator, V-65 (2,2′-azobis (2,4-dimethylvaleronitrile): manufactured by Wako Pure Chemical Industries, Ltd.) was added to a concentration of 0.01 mol / L, and under a nitrogen atmosphere, After stirring and polymerizing at 55 ° C. for 4.5 hours, the substance deposited by dropping in distilled water was collected and dried, and a copolymer of HEMA / DE = 95/5 (mol% ratio) (hereinafter RAG5) was collected. Abbreviated).

Example 1
<Nonwoven fabric>
The following polyethylene terephthalate (hereinafter abbreviated as PET) nonwoven fabric was used.
-The pre-filter material (low density filter part) has an average fiber diameter of 15 μm, a basis weight of 30 g / m ² , and a PET nonwoven fabric with an average pore diameter of 120 μm. / M ² , PET nonwoven fabric with an average pore diameter of 5.0 μm

<Preparation of coating solution>
-RAG5 was dissolved in ethanol to a concentration of 1.0 g / L to prepare a RAG5 coating solution.

<Nonwoven fabric coating>
The main filter material was immersed in the RAG5 coating solution at 20 ° C. for 5 minutes, then placed in a stainless steel basket and dried at 50 ° C. for 1.5 hours. Subsequently, the nonwoven fabric was washed with water and then placed in a stainless steel basket and dried at 50 ° C. for 3 hours to obtain a coated nonwoven fabric used for the high-density filter part.

<Nonwoven fabric disc production>
Using a rectangular punching blade, the prefilter material and the coated non-woven fabric were punched into the square dimensions shown in FIG. 1 to prepare a prefilter material and a main filter material.

<Filter preparation>
6 sheets of pre-filter materials and a main filter in a rectangular filter having a height (t1) of 0.6 mm for the upstream flow path forming rib 2A and a height (t2) of 0.8 mm for the downstream flow path forming rib 3A 36 materials were inserted to produce a filter.
The inlet of the filter and the blood bag were connected with a 40 cm long vinyl chloride tube (outer diameter 5 mm, inner diameter 3 mm). The outlet of the filter and the blood collection bag were connected with a 75 cm long vinyl chloride tube (outer diameter 5 mm, inner diameter 3 mm).

<Filter evaluation>
450 mL of bovine blood added with 10% trisodium citrate 5% aqueous solution as an anticoagulant for 100 mL of bovine blood was placed in a blood bag, and the blood was brought to 4 ° C. using a refrigerator. The filtered blood was collected in a blood collection bag. The time from the start of filtration to the emptying of the blood bag was defined as the filtration time. The results are shown in Table 1.

(Example 2)
Except for the rectangular filter in which the height (t1) of the upstream side flow path forming rib 2A is 0.8 mm and the height (t2) of the downstream side flow path forming rib 3A is 1.2 mm, it is the same as in Example 1. Thus, a filter was produced. The produced filter was evaluated in the same manner as in Example 1, and the results are shown in Table 1.

(Example 3)
4 except that the upstream side flow path forming rib 2A has a height (t1) of 0.6 mm and the downstream side flow path forming rib 3A has a height (t2) of 0.8 mm. A filter was produced in the same manner as in Example 1. The produced filter was evaluated in the same manner as in Example 1, and the results are shown in Table 1.

Example 4
7 except that the upstream flow path forming rib 2A has a height (t1) of 0.6 mm and the downstream flow path forming rib 3A has a height (t2) of 0.8 mm. A filter was produced in the same manner as in Example 1. The produced filter was evaluated in the same manner as in Example 1, and the results are shown in Table 1.

(Comparative Example 1)
Except for the rectangular filter in which the height (t1) of the upstream flow path forming rib 2A is 0.1 mm and the height (t2) of the downstream flow path forming rib 3A is 0.1 mm, the same as in the first embodiment. Thus, a filter was produced. The produced filter was evaluated in the same manner as in Example 1, and the results are shown in Table 1.

(Comparative Example 2)
Except for the rectangular filter in which the height (t1) of the upstream side flow passage forming rib 2A is 2.5 mm and the height (t2) of the downstream side flow passage forming rib 3A (2.5 mm), it is the same as in the first embodiment. Thus, a filter was produced. The produced filter was evaluated in the same manner as in Example 1, and the results are shown in Table 1.

From the results of Table 1, the sum (t1 + t2) of the height t1 of the upstream flow path forming rib 2A and the height t2 of the downstream flow path forming rib 3A is set to 1.0 mm or more, and the upstream flow path formation is performed. The filters of Examples 1 to 4 in which the rib 2A height t1 and the downstream flow path forming rib 3A height are 0.5 mm or more, respectively, have high blood circulation performance (blood filtration time is short). I understand that.
Further, in Comparative Example 2 in which (t1 + t2) is 5 mm, the blood filtration time is long, and therefore (t1 + t2) is less than 5 mm in the present invention.
Furthermore, it can be seen that the blood passing performance is high even if the filter shape is a hexagonal shape or a circular shape other than the rectangular shape.

A Leukocyte removal filter F Filter material F1 Pre-filter material (low density filter part)
F2 main filter material (high density filter part)
t1 Height of the upstream flow path forming rib t2 Height of the downstream flow path forming rib 1 Container 2 Upstream container main body 2A Upstream flow path forming rib 2B Outer peripheral side rib 3 Downstream side container main body 3A Downstream flow Path forming rib 3B Outer peripheral side rib 4 Inlet 5 Outlet 6 Outlet channel

Claims (4)

The filter material comprising a non-woven fabric or porous filter material, an upstream container body forming an upstream flow path of the filter material, and a downstream container body forming a downstream flow path of the filter material , An inflow port communicating with the upstream container body, an outlet port communicating with the downstream container body, and an upstream flow path forming rib provided on the inner surface of the upstream container body And a leukocyte removal filter comprising a downstream flow path forming rib provided on the inner surface of the downstream container body,
The height (t1) of the upstream flow path forming rib and the height (t2) of the downstream flow path forming rib are 0.5 mm or more (t1 ≧ 0.5 mm, t2 ≧ 0.5 mm). The sum (t1 + t2) of the height (t1) of the upstream flow path forming rib and the height (t2) of the downstream flow path forming rib is 1 mm or more and less than 5 mm (1 mm ≦ (t1 + t2) < 5 mm) Leukocyte removal filter.   The leukocyte removal filter according to claim 1, wherein the downstream container body is provided with a discharge channel. The filter material comprising a non-woven fabric or porous filter material, an upstream container body forming an upstream flow path of the filter material, and a downstream container body forming a downstream flow path of the filter material , An inflow port communicating with the upstream container body, an outlet port communicating with the downstream container body, and an upstream flow path forming rib provided on the inner surface of the upstream container body And a method for designing a leukocyte removal filter comprising a downstream flow path forming rib provided on the inner surface of the downstream container body,
The height (t1) of the upstream flow path forming rib and the height (t2) of the downstream flow path forming rib are set to 0.5 mm or more (t1 ≧ 0.5 mm, t2 ≧ 0.5 mm). The sum (t1 + t2) of the height (t1) of the upstream flow path forming rib and the height (t2) of the downstream flow path forming rib is 1 mm or more and less than 5 mm (1 mm ≦ (t1 + t2) < 5 mm) A leukocyte removal filter design method.   Furthermore, the design method of Claim 3 which designs so that the said downstream container main body may be equipped with an outlet flow path.

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