WO1989002305A1

WO1989002305A1 - Leucocyte-separating filter

Info

Publication number: WO1989002305A1
Application number: PCT/JP1988/000943
Authority: WO
Inventors: Keiji Naoi
Original assignee: Terumo Kabushiki Kaisha
Priority date: 1987-09-18
Filing date: 1988-09-16
Publication date: 1989-03-23
Also published as: JPS6475015A; KR890701183A

Abstract

A leucocyte-separating filter is disclosed, which has a porous membrane having fine pores with substantially an oblong form of 3 to 30 mum in average shorter diameter and a long diameter-to-short diameter ratio (average) of 1.5 or more. Leucocytes contained in a leucocyte suspension are collected without passing through the fine pores since the short diameter of the porous membrane is small enough, whereas since the pores have an oblong form, suspension-passing rate is comparatively great to effectively separate leucocytes. In addition, since matrix of the porous membrane is of a continuous structure, it is stable, and problems of run-off of foreign matters from the porous body or channeling of flow path during the procedure do not substantially arise.

Description

Memo Book White blood cell separation filter

[Technical field]

The present invention relates to a filter for separating leukocytes. More specifically, the present invention relates to a leukocyte separation filter that exhibits stable and efficient capture of leukocytes.o

[Background technology]

The form of ring blood has long changed from conventional whole blood ring blood to component blood transfusion, which requires only patients to transduce only the blood components.However, in this blood transfusion, how much The challenge is to increase the purity.

Conventionally, blood obtained by donating blood is separated into red blood cell concentrate (CRC), platelet-rich plasma (PC) and platelet-poor plasma (PPP) by centrifugation. The erythrocyte concentrate separated in this way is used as a component preparation of erythrocytes, and is widely used for component blood in patients who need erythrocytes. <The erythrocyte concentrate contains many white blood cells and platelets. The concept of a so-called whole blood component is becoming established, and patients who need only red blood cells are transfused with a large amount of white blood cells and platelets together with the red blood cell concentrate. It has been problematic. Thus, the white blood cells and platelets contained in the red blood cell fraction, such as red blood cell concentrate, have side effects after transfusion. In order to prevent this, it is necessary to remove as much as possible. For this reason, more efforts have been made than before.

Methods for increasing the purity of red blood cell preparations include gravity centrifugation using the specific gravity difference of blood cells, use of a trapping material using the action of adhesion or adhesion of blood cells, and separation of white blood cells using a red blood cell agglutinating agent. The method is used.

Among these methods, the method using a trapping material is widely used because of its high leukocyte removal efficiency and the simplicity of the procedure. ₍ Natural cellulose, polyester, boriamid, boriacrilonitrile, glass It is used in many cases where very small fibers such as fibers with a very small fiber diameter are packed in a column as they are, and those processed secondarily into nonwoven fabrics and the like.

However, in the above-mentioned method, it is difficult to uniformly fill the fiber when the fiber itself is packed in a column, and it takes time and effort to manufacture the fiber. However, if the packing density of the fibers is increased so that the leukocytes are sufficiently trapped, the filtration time becomes very long, and in addition, during the operation due to insufficient entanglement of the fibers. There was a risk that fibers would flow out. When the fibers are processed into a nonwoven fabric or the like, the above-mentioned problems are unlikely to occur, but the clogged blood cells are liable to be clogged. The acquisition material which shows stable performance is still available It is not at present.

Accordingly, an object of the present invention is to provide a novel filter for removing leukocytes. Another object of the present invention is to provide a leukocyte removal filter which has high and stable capturing ability for leukocytes and can separate leukocytes more efficiently from blood. Another object of the present invention is to provide a leukocyte removal filter capable of performing a safe leukocyte removal operation without fear of outflow of foreign matter during operation. Another object of the present invention is to provide a filter for removing leukocytes, which simplifies the manufacturing process of the filter and has less variation in product performance.

[Disclosure of the Invention]

The above objectives are as follows: the pore shape is substantially ft-circular, the average value of the minor axis is 3 to 30 oi, and the average value of the major axis is 1.5 times or more the average value of the minor axis. This is achieved by a leukocyte separation filter characterized by having a porous membrane.

The present invention also provides a leukocyte separation filter wherein the porosity of the porous membrane is from 20 to 85%. The present invention also provides a leukocyte separation filter in which the porous membrane is made of a fluororesin. In the present invention, the porous membrane further comprises poly (vinyl chloride), polyvinylidene fluoride, polyvinyl chloride, polyvinylidene fluoride, tetrafluoroethylene copolymer, and vinylidene fluoride hexafluoropro Pyrene copolymer, vinylidene fluoride-propylene copolymer, FIG. 1 shows a leukocyte separation filter selected from the group consisting of a trafluoroethylene-propylene copolymer and a tetrafluoroethylene-ethylene copolymer.

[Brief description of drawings]

FIG. 1 is a cross-sectional view showing an embodiment of the leukocyte separation filter of the present invention, and FIG. 2 is a circuit diagram showing a blood processing circuit incorporating the embodiment of the leukocyte separation filter of the present invention. FIG. 3 is an electron micrograph showing the fine structure of one embodiment of the porous membrane used in the leukocyte separation filter of the present invention.

BEST MODE FOR CARRYING OUT THE INVENTION The leukocyte-removing filter of the present invention has a pore shape substantially in the shape of an ellipse, and the average value of its minor axis is 3 to 30 in. Further, the present invention is characterized by having a porous membrane having an average value of the major axis of which is at least 1.5 times the average value of the minor axis. When a leukocyte suspension such as blood or erythrocyte concentrate is treated with such a porous membrane, the leukocytes contained in the leukocyte suspension have a pore diameter of 3 to 30 in the porous membrane. μm., so that they are trapped without passing through the pores. On the other hand, the major axis of the pores is more than 1.5 times the minor axis and the pore area is relatively large. In order to achieve this, the liquid permeation rate is fast enough to efficiently separate leukocytes. Furthermore, the matrix of the porous membrane is stable due to its continuous structure, In addition, problems such as outflow of foreign matter from the porous body or channel channeling in the flow path do not essentially occur.

Hereinafter, the present invention will be described in more detail based on embodiments. In the filter for separating leukocytes of the present invention, the pore shape is substantially oval, the average value of the minor axis is 3 to 30 ^ in, and the average value of the major axis is the average value of the minor axis. It is characterized by having a porous membrane that is at least 1.5 times as large as the above. In the porous membrane according to the present invention, the pore shape does not need to be strictly elliptical. If the pore has a similar shape to a circle in which the major axis and minor axis are different, some irregularities are present on the circumference. It may be one or a slit. Thus, in the leukocyte separation filter of the present invention, such a pore shape greatly affects the blood cell fractionation characteristics and the liquid permeation rate. That is, the particle size of the fraction depends on the minor diameter of the pores, while the liquid permeation rate depends on the area of the pores, so that the pore shape of the porous membrane is substantially oblong. Furthermore, if the relationship between the minor axis and the major axis is optimized, leukocytes contained in leukocyte suspensions such as blood and red blood cell concentrates can be efficiently captured with high precision. It becomes something.

In the porous membrane according to the present invention, the average value of the minor axis of the substantially oval pores is set to 3 to 30 m when the average value of the minor axis is less than 3 ^ ιη. When processing leukocyte suspensions such as blood and erythrocyte concentrates, even red blood cells contained in leukocyte suspensions are trapped, and the red blood cell recovery rate decreases. _{As a result,} overwhelmingly large numbers of red blood cells are caught and cause clogging in the filter.

If it exceeds 30 ^ in, the major diameter of the pores naturally exceeds this, and the pores become significantly larger.Therefore, the ability to capture leukocytes is reduced, and the membrane strength is reduced. It is because it disappears. In the porous membrane according to the present invention, the average value of the major axis of the substantially oval pores is set to 1.5 times or more of the average value of the minor axis if the major axis is smaller than this. This is because an improvement in the pore area cannot be expected, and a desired filtration efficiency cannot be obtained. The upper limit is not particularly limited, but is preferably about 5 times from the viewpoint of film strength. Further, in the porous membrane according to the present invention, it is desirable that the minor axis of the substantially oval-shaped pore is 3 to 15 μιπ. Since the pores of the porous membrane according to the present invention are quite large, and the measurement by the mercury porosimeter method and the butanol impregnation method is not appropriate as the method for measuring the pore diameter, a measurement method using a microscope is preferable. Things. The average value of the major axis and minor axis of the pores described in this specification is obtained by measuring the major axis and minor axis of 50 randomly selected pores from electron micrographs, and arithmetically calculating them. It is the average value.

Further, in the porous membrane according to the present invention, the porosity is preferably 20 to 85%, more preferably 40 to 80%. The porosity of the porous membrane is an important factor that affects the membrane properties such as the liquid permeation rate. If the porosity exceeds 80%, the membrane strength may not be sufficient if the porosity exceeds 80%.

The material constituting the porous membrane according to the present invention is not particularly limited as long as it does not affect the blood components contained in the white blood cell suspension such as the blood to be processed and the red blood cell concentrate. For example, various resins such as fluororesin, olefin resin, vinyl chloride resin, acryl resin, vinyl acetate resin, polysulfone resin, and polycarbonate are preferably used. In view of the manufacturing technology and the physical properties of the porous membrane, fluororesins are preferred. Examples of the fluororesin include various homopolymers and copolymers such as random copolymers, block copolymers, and graft copolymers. Rifidani pinylidene, polyvinylidene vinyl, vinylidene fluoride-tetrafluoroethylene copolymer, vinylidene fluoride-hexafluoropropylene copolymer And vinylidene fluoride-propylene copolymer, tetrafluoroethylene-propylene copolymer, and tetrafluoroethylene-ethylene copolymer are preferred.

Further, as a method of obtaining a porous membrane having a substantially oval pore shape using the above-mentioned materials, the average value of the minor axis is 3 to 3 ° in and the average of the major axis is The value is not particularly limited as long as the value can be 1.5 times or more the average value of the minor axis, but, for example, pores are formed by hot stretching after film formation. Alternatively, a method may be employed in which the porous membrane obtained by a solvent extraction method or the like is further subjected to a stretching treatment so as to obtain a predetermined pore shape.

FIG. 1 is a cross-sectional view showing an embodiment of the leukocyte separation filter of the present invention. In the present embodiment, the filter for leukocyte separation 1 is provided with a porous membrane 5 having the above-described configuration in a housing 4 having a blood inlet 2 and a blood outlet 3 in a housing 4. It is cut off and provided. In such a leukocyte separation filter 1, in order to hold the porous membrane 5 in the housing 4, for example, liquid-permeable supports 6a and 6b are provided before and after the porous membrane 5, It is optional to sandwich the porous membrane 5 between the support members 6a and 6b. The leukocyte separation filter 1 is actually used, for example, incorporated in a circuit as shown in FIG. In the circuit shown in FIG. 2, the blood bag 7 containing the blood to be processed and the saline bag 8 containing the physiological saline are positioned above the leukocyte separation filter 1, and the clamps 9 respectively. a, 9b are connected to the blood inlet 2 of the leukocyte separation filter 1 by the liquid guiding tubes 10a, 10b, and below the leukocyte separation filter 1. A physiological saline collection bag 11 and a blood collection bag 12 for collecting the processed blood are located in the container, and a liquid guide tube 10 provided with clamps 9c and 9d, respectively. e, 1 ◦ d for leukocyte separation It is connected to the blood outlet 3 of the port 1. In the leukocyte separation operation, first, the clamps 9b and 9c are opened, physiological saline is poured from the saline bag 8 into the filter 1 for leukocyte separation with the clamps 9a and 9d closed, and the leukocyte separation is performed. Priming inside filter 1 for use. The physiological saline used for the priming is collected in a physiological saline collection bag 10. After performing the priming, the clamps 9b and 9c are closed, and then the clamps 9a and 9d are opened. Then, the blood fluid flows from the blood bag 7 to the leukocyte separation filter 1. In the leukocyte separation filter 1, when the blood passes through the porous membrane 5 having the above configuration, the leukocyte component is captured by the porous membrane 5, and the leukocytes are separated. The blood from which leukocyte components have been removed in this manner is collected in the communicating blood collection bag 12. After the blood has been flushed from the blood bag 7, in order to collect the blood remaining in the leukocyte separation filter 1, further close the clamp 9a, open the clamp 9b, and open the leukocyte separation filter 1. The remaining blood in the leukocyte separation filter 1 is pushed out again by flowing physiological saline into the blood collection bag 12 and collected in the blood collection bag 12.When almost all the blood has been collected, clamp 9d is closed and clamp 9c is closed. Then, the physiological saline used for blood collection is collected in the physiological saline collection bag 11 and the white blood cell separation operation is completed.

Hereinafter, the present invention will be described more specifically with reference to examples. Example 15 parts by weight of vinylidene polyfluoride, 80 parts by weight of acetone and 5 parts by weight of glycerin were dissolved at 100 under pressure to form a uniform solution. The resulting stock solution was cast on a glass plate, placed in a sealed container, 1 0 0 ° 1 the autogenous pressure C in the system. 5 § cell with pressure controls such that the K / cm ² The ton was removed. After 2 hours, the pressure was returned to normal pressure, and the obtained film was simultaneously stretched in water at 85 ° C by 4.5 times in the X direction and 1.5 times in the Y direction. The obtained film had an average minor axis of 3ιτι and an average major axis of 15 m, and had a porosity of 70% having oval pores. As shown in Fig. 3, the pore shape of this porous membrane was taken by electron micrograph of the porous membrane, and the short and long diameters of 50 randomly selected pores were measured. This is obtained by calculating the average value.

Using the porous membrane obtained in this manner, a leukocyte separation filter as shown in FIG. 1 was prepared, and CPD-added blood was applied to the leukocyte separation filter using a circuit as shown in FIG. Shed. The leukocyte removal rate calculated from the blood cell counts before and after the treatment was 96%.

[Industrial applications]

As described above, in the present invention, the pore shape is substantially oval, the average value of the minor axis is 3 to 3 0 111, and the average value of the major axis is 1.5 times the average value of the minor axis. Since the filter for leukocyte separation is characterized by having a porous membrane as described above, it has a high and stable trapping ability for leukocytes, blood, and erythrocytes. It can efficiently separate leukocyte components from leukocyte suspensions such as concentrated liquids, and can safely perform leukocyte removal operation without fear of foreign matter entering due to falling off of the filter medium during operation. For example, it can provide a red blood cell fraction used in component transfusions with higher purity and safety, and greatly contributes to medical and medical fields.

Further, in the leukocyte separation filter of the present invention, the porosity of the porous membrane is 20 to 85%, and the porous membrane is made of fluororesin, more preferably polyfluoride. Vinyl, vinylidene fluoride, polyfluorinated mouth vinyl, vinylidene fluoride-tetrafluoroethylene copolymer, vinylidene fluoride-hexafluoropropylene copolymer, It is composed of any one selected from the group consisting of vinylidene fluoride-propylene copolymer, tetrafluoroethylene-propylene copolymer, and tetrafluoroethylene-ethylene copolymer. Thus, it has more excellent physical properties and can capture leukocytes more efficiently.

Claims

The scope of the claims

1. Porous membrane whose pore shape is substantially elliptical, whose average minor axis is 3 to 3 ° m, and whose average major axis is at least 1.5 times the average minor axis. A filter for separating white blood cells, comprising:

2. The filter for separating leukocytes according to claim 1, wherein the porosity of the porous membrane is 20 to 85%.

3. The leukocyte separation filter according to claim 1, wherein the porous membrane is made of a fluororesin.

4. The porous membrane is made of poly (vinylidyl fluoride), poly (vinylidene fluoride), poly (trifluorochlorovinyl), poly (vinylidene fluoride) tetrafluoroethylene, vinylidene fluoride-hexafluoropropylene copolymer, vinylidene fluoride 4. The method according to claim 3, wherein the copolymer is any one selected from the group consisting of a propylene copolymer, a tetrafluoroethylene-propylene copolymer, and a tetrafluoroethylene-ethylene copolymer. White blood cell separation filter.