TWI743939B - Blood processing filter - Google Patents

Abstract

The subject of the present invention is to provide a blood processing filter that is excellent in white blood cell removal performance, filtration time (filtration speed), and blood recovery. The aforementioned problems can be solved by the following blood processing filter.

A blood processing filter comprising: a flexible container for an inlet and an outlet of blood, a filter material arranged between the inlet and the outlet in the flexible container, and a filter arranged on the flexible container The blood processing filter of a flow path ensuring member between the filter material and the outlet portion in a sexual container is characterized by: the filter material includes: a filter layer X1 including a filter configuration unit A1, and a filter configuration unit B The filter layer Y; the filter layer X1 is arranged between the filter layer Y and the flow path ensuring member; the ventilation resistance per unit thickness of the filter constituting unit A1 is 5.0Pa. s/m ² or more and less than 9.0Pa. s/m ² ; The ventilation resistance per unit thickness of the aforementioned filter constituting unit B is 9.0Pa. s/m ² or more; the ventilation resistance of the aforementioned filter layer X1 is 4.0kPa. s/m or more and 20.0kPa. s/m or less; the ventilation resistance of the aforementioned filter material is 55.0kPa. s/m or more and less than 75.0kPa. s/m.

Description

Blood processing filter

The present invention relates to a blood processing filter for removing undesired components such as agglutinates or white blood cells from liquid or blood containing blood components.

The present invention particularly relates to a blood processing filter for removing microaggregates or white blood cells that are the cause of side effects from whole blood preparations, red blood cell preparations, platelet preparations, plasma preparations, etc. for blood transfusion.

When whole blood collected from a donor is used as the raw material for blood component preparations such as red blood cell preparations, platelet preparations, and plasma preparations, the whole blood may contain undesirable micro-aggregates or white blood cells that are the cause of various blood transfusion side effects. Element. Therefore, in general, removal of undesirable components is carried out after blood collection or before the use of blood component preparations.

A method for removing undesired components such as white blood cells from whole blood or blood component preparations. Based on simple operation and low cost, blood treatment using a filter material made of a fibrous aggregate containing non-woven fabric or a porous structure with continuous pores, etc. The filtering method of the filter is popularized.

In the past, blood processing filters were widely used to fill hard containers such as polycarbonate with filter materials made of non-woven fabrics or porous bodies. However, due to the low gas permeability of the containers, it was difficult to apply as a sterilization device for blood sampling and separation. Step and the widely used steam sterilization problem. In addition, in a closed system, there may be cases in which leukocytes are removed from the whole blood preparation after blood collection, and then the blood processing filter is cut off and then centrifuged for component separation; or the whole blood is separated by centrifugation. In the case where leukocytes are removed after separation into a plurality of blood components, in the latter case, the blood processing filter is centrifuged together with the blood collection and separation device. At this time, the rigid container may damage the bag or catheter, and the rigid container itself cannot withstand the pressure during centrifugation and may be damaged.

As a solution to these problems, we developed a "flexible blood processing filter" that uses materials that are the same as or similar to those used by the bag of the blood collection and separation device with flexibility and excellent vapor permeability. .

Generally, when the blood is processed by a blood processing filter, the blood preparation to be processed is added, and the bag connected to the blood inlet side of the filter by a catheter is placed at a position 20 cm to 100 cm higher than the filter, and gravity is applied. The blood preparation is passed through the filter, and the filtered blood preparation is contained in a recovery bag connected to the blood outlet side of the filter by a catheter. The resistance of the filter material in the filter will produce pressure loss, which makes the space on the inlet side of the filter become positive pressure. In the case of a filter made of a flexible container, since the container is flexible, there is a tendency for the positive pressure to cause the container to expand into a balloon shape, causing the filter material to be squeezed into the container on the outlet side.

In addition, usually, the bag used to store the blood processed by the blood filter is placed at a position 50cm~100cm lower than the filter, and the blood moves to the flow path on the downstream side under the action of gravity, resulting in the outlet of the filter The side exhibits a tendency of negative pressure, and the flexible container is easily attached to the filter material.

That is, it has been pointed out previously that the filter material using a flexible container has a strong tendency to adhere to the outlet side container through a double force, so the flow of blood will be hindered without being obstructed. Method to obtain sufficient filtration flow rate and filtration performance.

The performance of the blood cell removal filter will be evaluated for the white blood cell removal performance, blood fluidity, and blood recovery volume. It is important that the balance can be exerted well. However, in particular, the leukocyte removal performance and blood fluidity have problems in both the above-mentioned reasons.

As a method to solve this problem, Patent Document 1 discloses a technique in which a flow path securing sheet is arranged as a flow path securing member between the filter medium and the outlet side container, and the outlet side flexible container is connected to the outlet side container during filtration. The filter materials are not tightly connected to form a continuous gap, so that the filtration flow rate and the white blood cell removal performance are both.

In addition, Patent Document 2 discloses a technique in which a filter layer composed of filter components with specific characteristics is used as a flow path ensuring member, and the filter layer with a specific thickness is arranged at the lowest flow of the filter medium in contact with the outlet side container. The position ensures that even if the filter material is in close contact with the outlet side container, voids will still be formed in the filter layer, and the filter layer can flow in the vertical direction relative to the thickness of the filter material to achieve a (higher) filtration flow rate.

【Prior Technical Literature】 【Patent Literature】

[Patent Document 1] Japanese Patent No. 5524340

[Patent Document 2] Japanese Patent No. 4172631

In Patent Document 1, since the flow path ensuring member itself does not have leukocyte removal performance, it is impossible to increase the leukocyte removal performance to the maximum upper limit. In addition, the flow path securing sheet may cause blood remaining in the flow path or between the first sealing part and the second sealing part, which increases the loss of the recovery volume of the liquid to be processed.

In Patent Document 2, the filter layer arranged at the most downstream position of the filter medium connected to the outlet side container, on the one hand, when the filter medium outlet side and the outlet side of the flexible container sheet are in close contact with each other, it can still stay inside under compression. The flow path is maintained, but if the amount of the filter layer (flow path securing member) is increased in order to increase the flow, there will be a problem that the recovery volume loss of the liquid to be treated will increase. In addition, if the amount of filter material is reduced, the white blood cell removal performance is reduced, and there is a problem that the white blood cell removal performance, the filtration flow rate, and the blood recovery volume cannot all be achieved with high performance at the same time.

Although these technologies have reached a usable level as products, there is still room for improvement in their balance.

The subject of the present invention is to provide a blood processing filter with excellent white blood cell removal performance, filtration time (filtration speed), and blood recovery.

In order to solve the above-mentioned problems, the inventors have conducted in-depth research and found that in the direction of blood flow, a denser filter layer, a sparse filter layer, and a flow path are sequentially arranged in the direction from upstream to downstream. The blood processing filter that secures parts can solve the aforementioned problems, and thus the present invention has been completed.

That is, the present invention relates to the following.

[1]

A blood processing filter comprising a flexible container having an inlet and an outlet for blood, a filter material arranged between the inlet and the outlet in the flexible container, and a filter arranged in the flexible container The blood processing filter of the member for ensuring the flow path between the filter medium and the outlet portion in the sexual container is characterized in that the filter medium includes a filter layer X1 including a filter configuration unit A1, and a filter layer including a filter configuration unit B Y; The filter layer X1 is disposed between the filter layer Y and the flow path ensuring member; the ventilation resistance per unit thickness of the filter constituting unit A1 is 5.0Pa. s/m ² or more and less than 9.0Pa. s/m ² ; The ventilation resistance per unit thickness of the aforementioned filter constituting unit B is 9.0Pa. s/m ² or more; the ventilation resistance of the aforementioned filter layer X1 is 4.0kPa. s/m or more and 20.0kPa. s/m or less; the ventilation resistance of the aforementioned filter material is 55.0kPa. s/m or more and less than 75.0kPa. s/m.

[2]

The blood processing filter as described in [1], wherein the flow path ensuring member includes a filter layer Z including a filter constituent unit P; the ventilation resistance per unit thickness of the filter constituent unit P is less than 0.5 Pa . s/m ² ; The ventilation resistance of the aforementioned filter layer Z is 0.08kPa. s/m or more and 0.16kPa. s/m or less.

[3]

The blood processing filter described in [2], wherein the ventilation resistance of the filter layer Z is 0.08kPa. s/m or more and 0.12kPa. s/m or less.

[4]

The blood processing filter according to any one of [1] to [3], wherein the filter material further includes a filter layer X2 including a filter constituent unit A2; and the filter layer X2 is disposed at the inlet portion and the Between the filter layers Y; the ventilation resistance per unit thickness of the aforementioned filter constituting unit A2 is 5.0Pa. s/m ² or more and less than 9.0Pa. s/m ² ; The ventilation resistance of the aforementioned filter layer X2 is 4.0kPa. s/m or more.

According to the present invention, it is possible to provide a blood processing filter with excellent white blood cell removal performance, filtration time (filtration speed), and blood recovery.

[Fig. 1] A schematic diagram showing an experimental device used in the leukocyte removal performance test of the blood processing filter implemented in the embodiment.

Hereinafter, the mode for implementing the present invention (hereinafter referred to as "this embodiment mode") will be described in detail. In addition, the present invention is not limited to the following embodiments, and can be implemented with various modifications within the scope of its purpose.

Hereinafter, unless otherwise specified, the term "blood" refers to liquids containing blood and blood components. Examples of liquids containing blood components include blood preparations. Examples of blood preparations include whole blood preparations, red blood cell preparations, platelet preparations, and plasma preparations.

<Blood Processing Filter>

An embodiment of the present invention relates to a blood processing filter comprising a flexible container having an inlet and an outlet for blood, and a flexible container disposed between the inlet and the outlet in the flexible container A filter material, and a blood treatment filter of a flow path ensuring member between the filter material and the outlet portion arranged in the flexible container, characterized in that the filter material includes a filter layer X1 including a filter constituent unit A1, and includes The filter layer Y of the filter constituting unit B; the filter layer X1 is arranged between the filter layer Y and the flow path ensuring member; the ventilation resistance per unit thickness of the filter constituting unit A1 is 5.0Pa. s/m ² or more and less than 9.0Pa. s/m ² ; The ventilation resistance per unit thickness of the aforementioned filter constituting unit B is 9.0Pa. s/m ² or more; the ventilation resistance of the aforementioned filter layer X1 is 4.0kPa. s/m or more and 20.0kPa. s/m or less; the ventilation resistance of the aforementioned filter material is 55.0kPa. s/m or more and less than 75.0kPa. s/m. By adopting such a structure, excellent performance in white blood cell removal performance, filtration speed, and blood recovery can be exerted.

In the blood processing filter of this embodiment, the filter layer Y, the filter layer X1, and the flow path ensuring components are sequentially arranged from the inlet portion to the outlet portion of the flexible container. Therefore, the blood to be processed enters the flexible container through the inlet, sequentially passes through the filter layer Y, the filter layer X1, and the flow path ensuring member, and flows out of the flexible container through the outlet.

In the range that does not detract from the effect of the present invention, the filter material may include further filters. Filter layer. For example, the ideal filter medium further includes a filter layer X2 containing the filter constituent unit A2. In addition, the filter layer X2 is ideally arranged between the inlet portion and the filter layer Y. In this embodiment, the blood to be processed enters the flexible container through the inlet, passes through the filter layer X2, the filter layer Y, the filter layer X1, and the flow path ensuring components in sequence, and flows out of the flexible container through the outlet. Sex container.

Although the shape of the blood treatment filter of this embodiment is not particularly limited, it is ideally like the blood treatment filter described in Figure 14 of International Publication No. 2015/050216, which is composed of a filter material and a flexible container, and has a filter material throughout The entire circumference of the peripheral portion and the sealing portion area integrated with the flexible container; further, it is ideal to have a first sealing portion area that is integrated with the flexible container over the entire circumference of the filter material A second sealing area where the inlet flexible container and the outlet-side flexible container are integrated over the entire circumference of the outside of the sealing area, and an unsealed area between the first sealing area and the second sealing area.

The outer shape of the blood processing filter can be rectangular, disc, oblong, elliptical, etc. Since the material loss during manufacturing is less, the rectangular shape is ideal. Therefore, the following implementation forms Take the rectangular shape as an example.

〔Flexible container〕

The flexible container is preferably a container molded from a sheet-like molded object or a cylindrical molded object of a flexible resin. The flexible resin is preferably a flexible synthetic resin, and more preferably a flexible thermoplastic resin. The flexible resin is preferably one that is similar in thermal and electrical properties to the filter material. Flexible resins include, for example, soft polyvinyl chloride, polyurethane, ethylene-polyethylene acetate copolymers, polyolefins such as polyethylene and polypropylene, hydrogenated styrene-butadiene rubber-styrene copolymers, benzene Thermoplastic elastomers such as ethylene-isoprene-styrene copolymers or their hydrogenated products, and mixtures of thermoplastic elastomers with softeners such as polyolefins and ethylene-ethyl acrylate. The flexible resin is preferably soft polyvinyl chloride, polyurethane, ethylene-polyethylene acetate copolymer, polyolefin, and thermoplastic elastomers with the main components thereof, and more preferably soft polyvinyl chloride and polyolefin. In addition, it is more desirable to be a flexible container made of a material ^{with a tensile modulus of 7N/mm 2} to 13N/mm ^{2 and a thickness of 0.2mm to 0.6mm.} Tensile modulus of elasticity refers to the range of a linear relationship between tensile stress (load per unit area applied to the sample) and strain (elongation rate of the sample in the tensile direction) during a tensile test , The ratio of the tensile stress to the corresponding strain. In fact, it is based on JISK 7113 (Plastic Tensile Test Method), using an autograph (manufactured by Shimadzu Corporation, model AG-5KNI) and a force gauge (manufactured by Shimadzu Corporation, model SLBL) -500N) Perform a tensile test of the flexible container material. Use the data processing software "TRAPEZIUM" (manufactured by Shimadzu Corporation). Elastic modulus.

〔Filter material〕

The filter material is a member that processes blood, and more specifically, is a member that removes undesirable components such as agglutinates and leukocytes from the blood. The filter material includes at least a filter layer X1 and a filter layer Y, ideally includes a filter layer X1, a filter layer X2, and a filter layer Y, and more ideally is composed of only a filter layer X1, a filter layer X2, and a filter layer Y.

The filter layer contains the filter constituent units. When the number of filter constituent units is 1, it constitutes a filter layer by itself. When the number of filter constituent units is 2 or more, a plurality of filter constituent units are stacked to form a filter layer. The number of filter components is selected so that the filter layer has a specified ventilation resistance.

The filter layer X1 includes a filter configuration unit A1. Filter layer X1, can be In addition to the filter configuration unit A1, further filter configuration units are included, but it is ideal to be constituted by only one or more filter configuration units A1.

The filter layer X2 includes a filter configuration unit A2. The filter layer X2 may include further filter structural units in addition to the filter structural unit A2, but it is ideally constituted by only one or more filter structural units A2.

The filter layer Y includes a filter constituent unit B. The filter layer Y may include further filter structural units in addition to the filter structural unit B, but it is ideally constituted by only one or more filter structural units B.

The shape of the filter constituent unit is not particularly limited as long as it has micropores that can filter blood and has a specified ventilation resistance, but it is ideally a woven, woven, or non-woven fabric made of natural fibers, synthetic fibers, glass fibers, etc. Such as fibrous media, porous membranes, sponge-like structures with three-dimensional mesh-like continuous pores.

The material of the filter constituent unit is not particularly limited as long as it is hard to inflict damage to blood cells. The material of the filter constituent unit includes, for example, organic polymer materials, inorganic polymer materials, metals, and the like. Among them, organic polymer materials are excellent in processing properties such as cutting and are therefore ideal. The specific materials of the filter constituent unit include, for example, polyester, polyolefin, polyacrylonitrile, polyamide, polystyrene, polymethyl methacrylate, polyvinyl fluoride, polyurethane, polyvinyl alcohol, and polyvinyl condensation. Aldehydes, polyvinylidene, polyvinylidene fluoride, polychlorotrifluoroethylene, vinylidene fluoride-tetrafluoroethylene copolymer, polyether turpentine, polyacrylate, butadiene-acrylonitrile copolymer, polyether-polyamide intercalation Segment copolymers, ethylene-vinyl alcohol copolymers, cellulose, cellulose acetate, etc. are preferably polyesters, polyolefins, and particularly preferably polyesters.

Filter structure unit A1, filter structure unit A2, and filter structure The shape of the unit B may be the same or different as long as they have specified ventilation resistances. Although not particularly limited, the shapes of the filter structural unit A1, the filter structural unit A2, and the filter structural unit B are desirably a fibrous medium, and more desirably a non-woven fabric.

The material of the shape of the filter configuration unit A1, the filter configuration unit A2, and the filter configuration unit B may be the same or different as long as they have a specified ventilation resistance. Although not particularly limited, the material of the filter structural unit A1, the filter structural unit A2, and the filter structural unit B is preferably polyester.

The ventilation resistance per unit thickness of the filter constituting unit A1 is 5.0Pa. s/m ² or more and less than 9.0Pa. s/m ² , ideally 5.0Pa. s/m ² or more and less than 8.0Pa. s/m ² . By making the ventilation resistance per unit thickness of the filter constituent unit A1 within the above range, even when the filter material is in close contact with the container on the outlet side during filtration, the flow path in the filter constituent unit A1 can be maintained. The flow of the stream is not hindered, and sufficient filtration flow rate and filtration performance can be obtained. In this application, if the ventilation resistance per unit thickness of the filter constituting unit A1 is less than 5.0Pa. s/m ² , sufficient white blood cell removal performance cannot be obtained, and the number of residual white blood cells after filtration will exceed 5.5Log. If the ventilation resistance per unit thickness of the filter constituting unit A1 is 9.0Pa. s/m ² or more, a sufficient filtration flow rate cannot be obtained, and the filtration time becomes 27 minutes or more.

The ventilation resistance per unit thickness of the filter constituting unit A2 is ideally 5.0Pa. s/m ² or more and less than 9.0Pa. s/m ² , more preferably 5.0Pa. s/m ² or more and less than 8.0Pa. s/m ² . By setting the ventilation resistance per unit thickness of the filter constituent unit A2 within the above-mentioned range, it is possible to exhibit excellent performance in terms of leukocyte removal performance and filtration speed.

The ventilation resistance per unit thickness of the filter constituting unit B is 9.0Pa. s/m ² or more, ideally 9.0Pa. s/m ² or more and less than 30.0Pa. s/m ² , further preferably 12.0 Pa. s/m ² or more and less than 20.0Pa. s/m ² . By setting the ventilation resistance per unit thickness of the filter constituent unit B to the above range, it is possible to exhibit excellent performance in terms of leukocyte removal performance. In this application, if the ventilation resistance per unit thickness of the filter constituting unit B is less than 9.0Pa. s/m ² , sufficient white blood cell removal performance cannot be obtained, and the number of residual white blood cells after filtration will exceed 5.5Log.

The ventilation resistance of the filter layer X1 is 4.0kPa. s/m or more and 20.0kPa. s/m or less, ideally 11.0kPa. s/m or more and less than 16.0kPa. s/m. By setting the ventilation resistance of the filter layer X1 within the above range, excellent performance in terms of white blood cell removal performance, filtration speed, and blood recovery can be exerted. In this application, if the ventilation resistance of the filter layer X1 is less than 4.0kPa. s/m. Even if it is a suitable design for the filter constituent unit A1, the amount of the filter constituent unit A1 is still insufficient, resulting in the inability to obtain a sufficient filtration flow rate, and the filtration time will become more than 27 minutes. In addition, if the ventilation resistance of the filter layer X1 is 20.0kPa. Above s/m, the white blood cell removal performance cannot be obtained, and the number of residual white blood cells after filtration will exceed 5.5 Log, or the residual blood volume in the filter will increase, reducing the blood recovery volume.

The ventilation resistance of the filter layer X2 is ideally 4.0kPa. s/m or more, further preferably 11.0kPa. s/m or more and less than 16.0kPa. s/m. By setting the ventilation resistance of the filter layer X2 within the above-mentioned range, excellent performance in white blood cell removal performance and filtration speed can be exerted.

The air resistance of the filter material (the total air resistance of all filter layers constituting the filter material) is 55.0kPa. s/m or more and less than 75.0kPa. s/m, ideally 60.0kPa. s/m above and less than 67.0kPa. s/m. By setting the ventilation resistance of the filter material within the above-mentioned range, the leukocyte removal performance expected as a blood processing filter can be exhibited at a moderate filtration speed. In this application, if the ventilation resistance of the filter material is less than 55.0kPa. s/m, even if the aforementioned filter constituent units A1, A2, B and the aforementioned filter layers X1, X2, Y are designed as described in this application, the filtration flow rate will still be If it becomes too high, sufficient white blood cell removal performance cannot be obtained, and the number of residual white blood cells after filtration will exceed 5.5Log. In addition, if the ventilation resistance of the filter material is 75.0kPa. s/m or more, even if the aforementioned filter constituent units A1, A2, B and the aforementioned filter layers X1, X2, Y are designed as described in this application, the filtration flow rate will still be too low, and the filtration time will be 27 minutes or more.

The "ventilation resistance" (kPa·s/m) in this manual refers to the value measured when the sample (filter material, filter layer, or filter constituent unit) passes through a certain flow of air. The ventilation resistance was measured by the method described in the examples.

The "ventilation resistance per unit thickness" (Pa·s/m ² ) of the filter constituent unit is the "ventilation resistance" (kPa·s/m) of the filter constituent unit divided by the "thickness of the filter constituent unit""(Mm) value. The "thickness" (mm) of the filter constituent unit is measured by the method described in the examples.

The method of controlling the ventilation resistance of the filter constituent unit is not particularly limited. For example, when the filter constituent unit is a non-woven fabric, the ventilation resistance can be adjusted by changing the fiber diameter or density of the non-woven fabric. When the basis weight or density of the non-woven fabric is the same, by fine-tuning the fiber diameter of the non-woven fabric, for example, the specific surface area can be increased, and the ventilation resistance will be higher. When the fiber diameter of the non-woven fabric is the same, by increasing the density, for example, the pore size can be reduced, and the ventilation resistance will increase.

The fiber diameter or density of the non-woven fabric can be adjusted based on the manufacturing conditions of the non-woven fabric. The manufacturing method of the non-woven fabric that is easy to adjust the fiber structure can be the melt-blown method. For example, by investigating spinning factors such as resin viscosity, melting temperature, discharge volume per single hole, heating gas temperature, heating gas pressure, and the distance between the spinning nozzle and the stacking net, a non-woven fabric with the desired ventilation resistance can be obtained. In addition, it can be based on conventional information (for example, "The basis and application of non-woven fabrics", P.119-127, issued on August 25, 2005, Japan Textile Machinery Association, etc.), by suitable Change the manufacturing conditions to manufacture non-woven fabrics with suitable ventilation resistance.

When measuring the ventilation resistance and thickness of the filter component unit of the filter material assembled in the product, disassemble the product to take out the filter component unit, and measure the ventilation resistance and thickness of each filter component unit. However, the thickness is measured at a distance of 1 cm or more from the welded part of the filter unit. Specifically, when the filter material is cut away from the container near the peripheral edge of the filter surface, and the filter material is composed of a plurality of filter constituent units, they are peeled off each other to obtain each filter constituent unit. The filter constituent unit in the product is separable and integrated with other filter constituent units.

High ventilation resistance means that the air is not easy to pass through. For example, when the filter material is composed of fibers, it means that the fibers are entangled in a tight or uniform state. Therefore, blood does not flow easily, clogging of blood cells increases, and the processing speed tends to decrease.

On the other hand, low ventilation resistance means that air is easy to pass through. For example, when the filter material is composed of fibers, it means that the fibers are entangled in a sparse or uneven state. Therefore, blood is easy to flow, the number of times of contact with white blood cells is reduced, and there is a tendency for the white blood cell removal performance to decrease.

It is not obvious that the filtering speed and the leukocyte removal performance can be improved by combining filter components with different ventilation resistances in a specific configuration. It is speculated that if the filter components with specific characteristics are arranged at a specific thickness on the upstream side of the flow path securing member, even if the flexible container on the outlet side is in close contact with the filter material during filtration, the blood in the filter material will not be degraded. The flow path can increase the filtration flow rate. Furthermore, it is inferred that this contributes to the increase of the effective filtration area. As a result, even if the filter constituent unit has a sparse structure, it can still exhibit the leukocyte removal performance. However, the present invention is not limited by this speculation mechanism.

In this application, the design of the aforementioned filter layers X2, Y, and flow path ensuring components are arranged in order, and sufficient filtration flow rate and white blood cell removal performance cannot be obtained, and white blood remains after filtration. If the number of balls exceeds 5.5Log, the filtering time will become more than 27 points.

〔Parts for ensuring flow path〕

The flow path securing parts refer to all the parts arranged between the filter medium and the outlet part. The flow path securing member is not particularly limited as long as it can inhibit the blocking of blood flow caused by the close contact between the filter medium and the flexible container on the outlet side during filtration. The flow path securing member includes, for example, a flow path securing sheet, a filter layer, and the like. In addition, the flow path securing member includes, for example, a tube arranged between the filter medium and the container (for example, refer to the specification of European Patent No. 0526678) to prevent the close contact between the filter medium and the container, and the concave-convex part (Japanese Japanese Patent Laid-Open No. 11-216179), a knitted fiber sieve inserted between the filter material and the container (International Publication No. 95/017236 Manual), and a flexible frame sheet inserted between the filter material and the container (International Publication No. 95 /017236 Manual) and so on.

The flow path ensuring component is not tightly connected between the outlet side flexible container and the filter material in the filtration to form a continuous gap, which helps to increase the filtration flow rate and the effective filtration area. In this application, when the flow path ensuring component is not used, a sufficient filtration flow rate cannot be obtained, and the filtration time will be over 27 minutes. In addition, the effective filtration area is reduced, and the leukocyte removal energy can be over 5.5 Log.

The flow path securing member desirably includes the filter layer Z including the filter constituent unit P. The filter layer Z may contain further filter structural units in addition to the filter structural unit P, but it is ideally constituted by only one or more filter structural units P.

The shape and material of the filter constituent unit P may be those described in the item of the above-mentioned [filter material]. The shape of the filter constituent unit P is preferably a fibrous medium, and more preferably a non-woven fabric. The material of the filter constituting unit P is preferably polyester.

The ventilation resistance per unit thickness of the filter constituting unit P is ideally less than 0.5Pa. s/m ² , more preferably 0.1Pa. s/m ² or more and less than 0.5Pa. s/m ² . By setting the ventilation resistance per unit thickness of the filter constituent unit P within the above-mentioned range, it is possible to exhibit excellent performance in terms of filtration speed.

The ventilation resistance of the filter layer Z is ideally 0.08kPa. s/m or more and 0.16kPa. s/m or less, more preferably 0.08kPa. s/m or more and 0.12kPa. s/m or less. By setting the ventilation resistance of the filter layer Z within the above range, the amount of filter material can be reduced, and the risk of blood remaining in the blood processing filter can be reduced.

<Manufacturing method of blood processing filter>

The spun filter constituent units A1 and B are layered, respectively, to obtain filter layers X1 and Y, and filter layers Y and X1 and flow path securing members are sequentially layered. If necessary, the layered filter constitutes the unit A2 to obtain the filter layer X2, and the layered filter layer X2 and the filter layer Y are adjacent to each other. The laminated body can be cut to a specified size using, for example, a blade, an ultrasonic cutting machine or a laser cutting machine to be used as a filter material.

The method of integrating the filter medium, the flow path securing member, and the flexible container is not particularly limited, and it can be integrated in the same manner as in conventional blood processors. For example, as described below, the blood processing filter (using a flexible frame as a flow path securing member) described in Figs. 1 to 3 of International Publication No. 2015/050216 can be integrated. A flexible container with an inlet portion and a flexible container with an outlet portion are integrated along the periphery of the filter material in a band-shaped seal while sandwiching the filter material. This belt-shaped adhering area along the periphery of the filter material is the inner sealing part (first sealing part). The inner sealing part is set so as not to include the peripheral end of the filter material. The inner side than the inner sealing part is the filtering part through which the blood flows.

The peripheral edge of the flexible container with the inlet portion and the flexible container with the outlet portion are sealed and integrated by a belt shape. As a result, a rectangular ring-shaped outer side sealing portion (second Sealing part). In addition, the formation of the inner sealing portion and the outer sealing portion can be welded by high-frequency welding, but it is not limited to this. Various bonding techniques such as ultrasonic welding and thermal welding can be used.

The blood inlet and outlet can also be integrated with the flexible container in advance by injection molding or other methods. Alternatively, holes or slits can be formed in the extruded sheet-like film or cylindrical film-formed product, where The inlet and outlet parts molded by individual injection molding or extrusion molding can also be connected in a liquid-tight and connected state by conventional techniques such as adhesives, heat sealing, or high-frequency welding. The latter is more desirable for reasons that deformation of the container is less likely to occur during steam sterilization and the manufacturing steps are easy.

In addition, when the sheet-like or cylindrical membrane is liquid-tightly mounted with the inlet and outlet parts including the tube, the material of the inlet and outlet parts can be the same as the sheet-like or cylindrical membrane. The material can also be other materials. In the case of other materials, as long as the inlet and the outlet can be joined to a sheet-like or cylindrical film without gaps and liquid-tightly, and does not impede operability, etc., there is no particular limitation on the material. However, in the case of joining by heat sealing or high-frequency welding suitable for mass production, it is ideal to be similar in thermal and electrical properties to a sheet-like or cylindrical film.

For example, in the case of soft polyvinyl chloride with high permittivity materials, it can be properly joined by high frequency welding; for example, in the case of polyolefin with low permittivity materials, it can be properly joined by heat sealing.

Example

Hereinafter, the present invention will be described in further detail with examples, but the present invention is not limited by the following examples.

The physical properties and performance of blood processing filters are determined by the following methods.

(Measurement of ventilation resistance of filter material, filter layer and filter unit)

A vent hole in the air permeability test apparatus (KatoTech stock company system, KES-F8-AP1) of (vent area 2πcm ² (φ 1.414cm)), placing the sample 5cm × 20cm size (filter, filter layer, or Filter constituent unit), measure the pressure loss (kPa·s/m) (the pressure difference between the two sides of the sample compartment) generated when air is ventilated ^{at 8πcm 3 /s for about 10 seconds, and set it as the ventilation resistance.}

(Measurement of the thickness of the filter component)

Cut out a 5cm×20cm sample from the filter components, place it on a dial thickness gauge (model: G, manufacturer: Ozaki Seisakusho), and measure its thickness (mm).

(Measurement of the ventilation resistance per unit thickness of the filter constituent unit)

Divide the aeration resistance (kPa·s/m) of the filter constituent unit measured in the aforementioned "(Measurement of the ventilation resistance of the filter material, filter layer and filter constituent unit)" by the aforementioned "(The thickness of the filter constituent unit) Measurement)" The thickness (mm) of the measured filter constituent unit, and the ventilation resistance per unit thickness of the filter constituent unit is obtained.

(White blood cell removal performance of blood processing filter)

The blood preparation used the erythrocyte preparation prepared according to the European standard (the Guide to the Preparation, Use and Quality Assurance of Blood Components 19th edition (2017)), and the blood of the Examples and Comparative Examples was used at a drop of 110 cm The inner filter is filtered and recovered to obtain the filtered blood preparation. Among them, the drop refers to the lowest part of the bag before the filtration of the red blood cell preparation to the lowest part of the recovery bag after the filtration of the red blood cell preparation (Figure 1).

Next, the white blood cell concentration in the blood preparation after filtration was measured using the set "LeucoCOUNT" for measuring the number of white blood cells manufactured by Beaton Dickinson (BD) and the flow cytometer FACS Canto II manufactured by BD, and the concentration of white blood cells in the filtered blood preparation was calculated according to the following formula The number of remaining white blood cells (rWBC) is used as an indicator of the white blood cell removal performance of the blood processing filter.

rWBC=log (the concentration of white blood cells in the blood preparation after filtration × the amount of blood preparation after filtration)

[Evaluation criteria]

◎: Less than 5.0

○: 5.0 or more but less than 5.5

×: 5.5 or more

(Filter time)

In the aforementioned "(White blood cell removal performance of blood processing filter)", the filtration time (minutes) is the time required for the red blood cell preparation to flow into the blood processing filter until the mass increase of the red blood cell preparation recovery bag stops after filtration (minutes). In addition, the cessation of the increase in the mass of the recovered bag refers to the point at which the change in the mass of the recovered bag becomes 0.1g or less when the quality of the recovered bag is measured every minute after the start of filtration. In the present embodiment, it is calculated by including the last minute of the stop judged as the mass increase in the filtering time.

[Evaluation criteria]

◎: Less than 24 points

○: 24 points or more but less than 27 points

×: 27 points or more

(Amount of blood recovered)

The blood loss (the difference between the blood volume before filtration and the blood volume after filtration) is evaluated as an indicator of the blood recovery volume. The blood volume before filtration is calculated by subtracting the weight of the empty bag set of the same type from the weight of the bag set containing the red blood cell preparation and the red blood cell storage solution before filtration. After filtration, cut the line connecting the blood processing filter and the recovery bag at a distance of 5 cm from the outlet of the blood processing filter. By subtracting the weight of the same type of recycling bag in the empty state from the weight of the recycling bag thus obtained Calculate the filtered blood.

[Evaluation criteria]

◎: Less than 25ml

○: 25ml or more and less than 30ml

×: more than 30ml

(Examples 1~5)

The filter configuration unit A1 and the filter configuration unit B use non-woven fabrics manufactured by the melt blown method. The filter constituent unit P uses a nonwoven fabric manufactured by spunbonding.

The filter constituent unit A1 is a PBT non-woven fabric with a thickness of 0.42 (mm) and a ventilation resistance per unit thickness of 5.2 (Pa·s/m ² ); in addition, the filter constituent unit B is a thickness of 0.41 (mm) and ventilation per unit thickness PBT non-woven fabric with a resistance of 10.4 (Pa.s/m ² ); the filter constituent unit P is a polyethylene terephthalate with a thickness of 0.20 (mm) and a ventilation resistance per unit thickness of 0.20 (Pa.s/m ²⁾ The non-woven fabrics were stacked in the number and order shown in Table 1 to form a laminate, which was cut into a size of 91cm×74cm using a laser cutter to make a filter material.

This filter material is sandwiched between two flexible polyvinyl chloride resin sheets that have the inlet or outlet of the blood. A high-frequency welding machine is used to weld the filter material and the peripheral part of the flexible sheet. , Make it integrated. In addition, the internal measurement of the welded part is a rectangular effective filtering part with a vertical dimension of 74mm, a horizontal dimension of 57mm, and a curved corner, with an effective filtering area of 42cm ² . The peripheral part of the flexible sheet is further welded and integrated to produce a blood processing filter. After the blood processing filter was subjected to high-pressure steam sterilization at 115°C for 59 minutes, the aforementioned leukocyte removal performance test was performed.

(Examples 6-10, 15, 17)

Except that the filter constituent unit A1 was changed to a PBT non-woven fabric with a thickness of 0.42 (mm) and a ventilation resistance per unit thickness of 7.3 (Pa·s/m ² ), the same method as in Example 1 was used to produce a blood processing filter. Perform a white blood cell removal performance test.

(Examples 11~13)

Except that the filter constituent unit A1 was changed to a PBT non-woven fabric with a thickness of 0.42 (mm) and a ventilation resistance per unit thickness of 8.7 (Pa·s/m ² ), the same method as in Example 1 was used to produce a blood processing filter. Perform a white blood cell removal performance test.

(Example 14)

Except that the filter component B was changed to a PBT non-woven fabric with a thickness of 0.41 (mm) and a ventilation resistance per unit thickness of 12.7 (Pa·s/m ² ), the same method as in Example 6 was used to produce a blood processing filter. Perform a white blood cell removal performance test.

(Examples 16, 18)

The filter constituting unit A2 uses a non-woven fabric manufactured by the melt-blown method.

Except that a PBT non-woven fabric with a thickness of 0.42 (mm) and a ventilation resistance per unit thickness of 7.3 (Pa·s/m ² ) was used for the filter constituent unit A2, the same method as in Example 14 was used to produce a blood processing filter and perform leukocytes. Removal performance test.

(Example 19)

The filter configuration units A1 and A2, and the filter configuration unit B use non-woven fabrics manufactured by the melt-blown method. As the flow path securing member, the inlet side frame sheet and outlet side frame sheet made of flexible polyvinyl chloride resin as described in International Publication No. 2015/050216 are used.

The filter constituent units A1 and A2 use PBT non-woven fabric with a thickness of 0.42 (mm) and a ventilation resistance of 7.3 (Pa·s/m ^{2) per unit thickness.} The filter component B uses a PBT non-woven fabric with a thickness of 0.41 (mm) and a ventilation resistance per unit thickness of 12.7 (Pa·s/m ^{2 ).} The filter configuration units A1 and A2, and the filter configuration unit B were stacked in the number and order shown in Table 3 to form a laminate, which was cut into a size of 91cm×74cm using a laser cutter to produce a filter material.

This filter material is sandwiched between the inlet side frame sheet and the outlet side frame sheet made of flexible polyvinyl chloride resin, and the peripheral part of the filter material is welded and integrated using a high frequency welding machine. In addition, the internal measurement of the welded part is a rectangular effective filtering part with a vertical dimension of 74mm, a horizontal dimension of 57mm, and a curved corner, with an effective filtering area of 42cm ² . Furthermore, the inlet side frame sheet and the outlet side frame sheet are sandwiched between two flexible polyvinyl chloride resin sheets that have ports that become the inlet or outlet of blood. The high-frequency welding machine is used for welding. The peripheral part of the flexible sheet is integrated to produce a blood processing filter. After the blood processing filter was subjected to high-pressure steam sterilization at 115°C for 59 minutes, the aforementioned various tests were performed.

(Comparative Examples 1, 2)

The evaluation was performed in the same manner as in Examples 6 to 10, except that the number of sheets of each filter constituent unit constituting each filter layer was changed as shown in Table 4.

(Comparative Examples 3 and 10)

The evaluation was performed in the same manner as in Example 14, except that the number of sheets of each filter constituent unit constituting each filter layer was changed as shown in Table 4 or Table 5.

(Comparative Example 4)

The evaluation was performed in the same manner as in Example 15 except that the number of sheets of each filter constituent unit constituting each filter layer was changed as shown in Table 4.

(Comparative Example 5)

Except as shown in Table 4, the number of sheets of each filter constituent unit constituting each filter layer is changed to Otherwise, the evaluation was carried out in the same manner as in Example 16.

(Comparative Example 6)

The evaluation was carried out in the same manner as in Example 19, except that the number of sheets of each filter constituent unit constituting each filter layer was changed as shown in Table 4.

(Comparative Example 7)

As shown in Table 5, the filter constituent unit A1 is replaced with a PBT non-woven fabric with a thickness of 0.42 (mm) and a ventilation resistance per unit thickness of 4.5 (Pa·s/m ² ). Other than that, the same as in Example 4 is used. The method is to make a blood filter and perform a white blood cell removal performance test.

(Comparative Example 8)

As shown in Table 5, the filter constituent unit A1 is replaced with a PBT non-woven fabric with a thickness of 0.42 (mm) and a ventilation resistance per unit thickness of 9.2 (Pa·s/m ² ). Except for this, the same as in Example 1 is used. The method is to make a blood filter and perform a white blood cell removal performance test.

(Comparative Examples 9, 11, 12)

As shown in Table 5, the filter component B has a thickness of 0.41 (mm) and a ventilation resistance per unit thickness of 8.8 (Pa·s/m ² ), and the number of filter components constituting each filter layer is changed. Except for this, it evaluated using the same method as Examples 6-10.

(Comparative Example 13)

The filter configuration unit A2 and the filter configuration unit B use non-woven fabrics manufactured by the melt-blown method.

The filter constituent unit A2 uses a PBT non-woven fabric with a thickness of 0.42 (mm) and a ventilation resistance of 7.3 (Pa·s/m ^{2) per unit thickness.} The filter component B uses a PBT non-woven fabric with a thickness of 0.41 (mm) and a ventilation resistance per unit thickness of 12.7 (Pa·s/m ^{2 ).} The filter configuration unit A2 and the filter configuration unit B are stacked in the number and order shown in Table 5 to form a laminate, which is cut into a size of 91 cm×74 cm using a laser cutter to prepare a filter material.

This filter material was made into a blood processing filter by the same method as in Example 1, and the leukocyte removal performance test was performed.

【Industrial Utilization】

The blood processing filter of the present invention can be used as a blood processing filter for removing undesired components such as agglutinates or leukocytes from liquid or blood containing blood components.

In particular, it can be used for the purpose of removing microaggregates or white blood cells that are the cause of various side effects from whole blood preparations, red blood cell preparations, platelet preparations, plasma preparations, etc. for blood transfusion, and can be suitably used as a disposable blood processing filter.

Claims (4)

A blood processing filter comprising a flexible container having an inlet and an outlet for blood, a filter material arranged between the inlet and the outlet in the flexible container, and a filter arranged in the flexible container The member for ensuring the flow path between the filter medium and the outlet portion in the sexual container is characterized in that the filter medium includes a filter layer X1 including a filter structural unit A1, a filter layer Y including a filter structural unit B; the aforementioned filter layer X1, arranged between the filter layer Y and the flow path ensuring member; the ventilation resistance per unit thickness of the filter constituting unit A1 is 5.0Pa. s/m ² or more and less than 9.0Pa. s/m ² ; The ventilation resistance per unit thickness of the aforementioned filter constituting unit B is 9.0Pa. s/m ² or more; the ventilation resistance of the aforementioned filter layer X1 is 4.0kPa. s/m or more and 20.0kPa. s/m or less; the ventilation resistance of the aforementioned filter material is 55.0kPa. s/m or more and less than 75.0kPa. s/m. The blood processing filter described in the first item of the scope of patent application, wherein the flow path ensuring member includes a filter layer Z including a filter constituent unit P; the ventilation resistance per unit thickness of the filter constituent unit P is not Full 0.5Pa. s/m ² ; The ventilation resistance of the aforementioned filter layer Z is 0.08kPa. s/m or more and 0.16kPa. s/m or less. Such as the blood processing filter described in item 2 of the scope of patent application, wherein the aforementioned filter layer Z The ventilation resistance is 0.08kPa. s/m or more and 0.12kPa. s/m or less. As for the blood processing filter described in any one of items 1 to 3 in the scope of the patent application, the filter material further includes a filter layer X2 containing a filter constituent unit A2; the filter layer X2 is disposed at the inlet and Between the aforementioned filter layers Y; the ventilation resistance per unit thickness of the aforementioned filter constituting unit A2 is 5.0Pa. s/m ² or more and less than 9.0Pa. s/m ² ; The ventilation resistance of the aforementioned filter layer X2 is 4.0kPa. s/m or more.

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