JPH06142196A - White blood cell removing filter - Google Patents

Abstract

PURPOSE:To efficiently remove not only white blood cells but platelets as well without changing pore sizes by using a filter medium consisting of a continuous porous material which has a surface zeta potential of a positive potential and communicates with the outside as a main constituting part. CONSTITUTION:This white blood cell removing filter is constituted by using the filter medium consisting of the continuous porous material which has the surface zeta potential of the positive and communicates with the outside as the main constituting part. In the white blood cell removing filter, the rate of removing not only the white blood cells but the platelets as well is improved by using the porous body having the surface zeta potential of the positive potential as the filter medium. Since the rate of removing the platelets is improved by changing the surface zeta potential, the filter having the large pore sizes is possible and the shortening of the time for treating the blood is possible. The surface zeta potential is easily changed by treating the material which makes the surface zeta potential positive, thereby the performance to capture the white blood cells and the platelets is changed.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a leukocyte removal filter having a high platelet removal rate. More specifically, the present invention relates to a leukocyte removal filter that removes leukocytes and more efficiently removes platelets.

[0002]

2. Description of the Related Art As the form of blood transfusion has changed from whole blood transfusion to component transfusion, more pure component preparations of red blood cells have been demanded. 200cc or 40
Blood obtained by donating 0 cc of blood is fractionated into various components by centrifugation. The red blood cell component is most often separated as a red blood cell concentrate and transfused into a patient in need of red blood cells. Since this red blood cell concentrate contains many white blood cells and platelets, side effects after blood transfusion are a serious problem. In particular, leukocytes often cause transfusion side effects, and may cause non-hemolytic febrile side effects, anti-leukocyte antibody production, graft-versus-host reaction, etc., so use a fiber or porous filter. It has been removed. In addition, when platelets are frequently transfused, it is desired to remove them in order to suppress the production of antiplatelet antibodies. Therefore, in order to increase the platelet removal rate with the conventional leukocyte removal filter, it was necessary to reduce the pore diameter in order to remove platelets that are originally smaller in size than white blood cells.

[0003]

However, in such a conventional leukocyte-removing filter, there is a problem that if the pore diameter of the porous body is reduced, a sufficient flow rate cannot be obtained and clogging is likely to occur. Therefore, an object of the present invention is to provide a leukocyte removal filter that more efficiently removes not only leukocytes but also platelets without changing the pore size.

[0004]

The above object can be achieved by the present invention described below. (1) The surface zeta potential (electrokinetic potential) is positive (0
A leukocyte-removing filter whose main part is a filter medium composed of a continuous porous body that is open to the outside and has a mV or more). (2) The leukocyte removal filter described in (1) above, which has a surface zeta potential of 3 mV or more. (3) A leukocyte removal device comprising the leukocyte removal filter according to any one of (1) and (2) above.

The "zeta potential" in the present invention is usually measured as follows. That is, when the solid and liquid are moved relative to each other, when the surface of the solid is negatively charged, a concentration gradient of ions is formed on the liquid side, and when the liquid is moved in that state, it is attracted to the solid surface + Of the ions, those off the slip surface move along with the flow of the liquid, while adsorbed ions near the surface of the solid are retained there. When the electrodes are placed upstream and downstream of this solid, the downstream electrode is positively charged and the upstream electrode is negatively charged, and the offshore ions are opposite to the flow of ions near the solid surface in order to eliminate this potential difference. + Ions move upstream and − ions move downstream. Then, under a constant liquid flow velocity, the behavior of the ions keeps a steady state, so that a constant potential difference is generated between the two electrodes, which is called "streaming potential".

The "zeta potential" refers to the potential on the surface where "slip" occurs in the flow of ions at this time, and is calculated by the following equation (Equation 1).

[0007]

[Equation 1] Where η is the viscosity of the flowing liquid, ε is the dielectric constant of the flowing liquid, and E
s is the streaming potential, λ is the conductivity of the flowing liquid, and P is the pressure applied to flow the fluid.

In the present invention, the "porous body" is a substance having continuous pores in the inside or on the surface thereof and leading to a large number of small outsides. That is, it is not particularly limited as long as it has a hole through which blood cells can pass. The material of the porous body may be an inorganic substance such as unglazed brick, a natural organic substance such as hemp, sponge, or a synthetic polymer such as plastic foam (foamed plastic). Further, it may have a sponge shape or a film shape. From the viewpoint of mass production, a synthetic resin porous body or the like is preferable, and examples thereof include polyurethane, fluororesin, polypropylene, polyvinyl formal, and polycarbonate. Regarding the pore size, as long as it is a porous body having large pores, one having a large thickness may be used, or one having a small thickness may be laminated and used, and a porous body having a small pore may be used as it is. By appropriately selecting the pore size and thickness of the porous body, any porous body can be used as long as it allows blood cells to pass through. In particular,
JP-B-63-26089 and JP-A-3-173825 disclose filters for removing leukocytes having an average pore diameter of 5 to 20 μm or 6 to 12 μm, and it is preferable to use a porous body having these pore diameters.

In order for the surface zeta potential to be a positive potential, the porous body itself of the main part of the filter medium may be a substance exhibiting a positive potential. Further, a positive potential may be exhibited by subjecting the porous body of the main part of the filter medium to a surface treatment. For example, there is a method in which a substance having a cationic functional group such as an amino group is introduced into the porous body of the base material by a chemical reaction to make the zeta potential of the porous body of the base material a positive potential.

Surface zeta potential is positive (0 mV or more)
The main filter part made of a porous material is incorporated in a filter housing as shown in FIG. A prefilter in which nonwoven fabrics having a single composition are laminated is arranged on the upstream side of the filter medium, and a spacer for preventing the filter medium and the housing from coming into close contact is arranged on the downstream side of the filter medium.

Further, the leukocyte removal filter of the present invention is
By hydrophilizing by a known method, the blood product is easily impregnated, and partial air block of the filter can be prevented.

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited thereto.

[0013]

【Example】

Example 1 1 g of a polyvinyl formal porous material (thickness: 1.3 mm) crosslinked with formaldehyde was added to 10 parts.
Soak in 0 ml of water, add 2.5 ml of a solution of cerium ammonium nitrate dissolved in 1N nitric acid to 0.1 mol / l, and further dissolve 5 g of acrylamide.
Polymerization was carried out at ℃ for 1 hour. The surface zeta potential was calculated by measuring the streaming potential, the pressure applied for flowing the liquid, and the electrokinetic rate of the liquid with a streaming potential measuring device. The fluid used is a 1 mM KCl aqueous solution, and the pH is 6 ±
1. Measured at a temperature of 20 ± 5 ° C. The zeta potential is +
It was 5.9 mV. The obtained sample was punched out into a holder of FIG. 1 to a diameter of 25 mm and put into it together with a 0.8 mm-thick prefilter and a mesh.

400 ml of human blood was collected in a CPD Terumo Double Bag (Terumo), centrifuged at 3000 rpm for 10 minutes, and 150 ml of the supernatant plasma was transferred to a child bag, and the remaining concentrated red blood cells contained 50 hematocrit. Physiological saline was added to prepare a erythrocyte suspension so that the amount of the erythrocyte was 0.1%. Twenty-five ml of the prepared red blood cell suspension was flown through the blood inlet 2, and the filtration time and the blood cell count before and after filtration were adjusted to Sysmex NE-600.
0 (manufactured by Toa Medical Electronics Co., Ltd.), and the removal rate was calculated according to the following formula (Equation 2).

[0015]

[Equation 2]

As a result, the leukocyte removal rate was 93.3%, the platelet removal rate was 91.4%, and the required time was 3 minutes 16 seconds.

Comparative Example 1 On the other hand, the surface zeta potential is −
When the same test was performed on the 22.8 mV polyvinyl formal porous body used in Example 1, the leukocyte removal rate was 9
The rate was 2.0%, the platelet removal rate was 65.5%, and the required time was 2 minutes and 29 seconds.

Example 2 A polyurethane porous filter (thickness: 0.5 mm) was washed with methanol in a Soxhlet washing machine for 8 hours, and then low temperature plasma (argon, 0.2 T) was used.
orr) was irradiated for 20 seconds. Subsequently, 4-vinylpyridine gas (0.6 Torr) was introduced into the reactor to carry out surface graft polymerization. The surface-grafted filter obtained is
A quaternization reaction was carried out in a solution containing 0.1 M benzyl chloride at 55 ° C. for 3 hours to obtain a polyurethane porous filter having N-benzylpyridinium chloride groups on the surface.

When the zeta potential of the filter was measured, it was +46.8 mV. When the obtained filter was evaluated in the same manner as in Example 1, the leukocyte removal rate was 99.8.
The rate was 9%, the platelet removal rate was 98.84%, and the required time was 4 minutes and 50 seconds.

Example 3 In the same manner as in Example 2, the same polyurethane porous filter was graft-polymerized with diethylamino acrylate and then reacted in a methanol solution containing 0.1 M ethyl bromide at 50 ° C. for 16 hours. Quaternization reaction was performed to obtain a polyurethane porous filter having a triethylammonium bromide group on the surface.

When the zeta potential of the filter was measured, it was +7.8 mV. When the obtained filter was evaluated in the same manner as in Example 1, the leukocyte removal rate was 99.73.
%, The platelet removal rate was 99.10%, and the required time was 4 minutes and 25 seconds.

Comparative Example 2 The zeta potential of the untreated polyurethane porous filter, which is the base material of Examples 2 and 3, was measured and found to be -40.0 mV. When the filter was evaluated in the same manner as in Example 2, the leukocyte removal rate was 9
The rate was 1.4%, the platelet removal rate was 5.1%, and the time required was 4 minutes and 39 seconds.

(Example 4, Comparative Example 3) With a thickness of 0.5 mm,
Polyurethane porous material filter material having a surface zeta potential of -30 mV, which has a leukocyte removal rate of about 30 to 60% at this thickness, and glycidyl acrylate are graft-polymerized on the polyurethane porous material, and then a cationizing agent (cationone UK: On the other hand, the leukocyte-removing ability was compared using a filter medium having a surface zeta potential of +7.9 mV. Filter holder (NUCLEPORE 25mm HOLDE) with a thickness of 0.5mm was punched out to a diameter of 25mm.
R), and using this, fresh whole blood, red blood cell concentrate and leukocyte suspension were filtered at a flow rate of 0.5 ml / min / cm ² for 10 minutes. The results are shown in Table 1. The leukocyte concentration in the liquid filtered using the cationization-treated filter medium is about 1/40 to 1/80 of the leukocyte concentration in the liquid filtered by each untreated porous body. It was shown to. The concentration of red blood cells did not change before and after filtration.

[0024]

[Table 1]

The electron microscopic observation of the porous body after filtration only showed leukocytes that could not pass through the pores in the untreated porous body but were trapped in the cationized porous body. It was confirmed that a large number of leukocytes were adsorbed on the surface of the base material as long as they were captured by the pore size. At the same time, platelet adsorption was also observed on the cationized surface. Thus, the cationization treatment and the positive surface zeta potential improve the capturing performance of leukocytes and platelets, but it can be judged that the influence on the recovery of red blood cells is small. It was also suggested that at the same time as the start-up time was shortened, the flow path formation in the filter was uniform.

[0026]

As described above in detail, the leukocyte-removing filter of the present invention has a removal rate of not only leukocytes but also platelets by using a porous material having a positive surface zeta potential as the main part of the filter medium. The removal rate of platelets can be improved by changing the surface zeta potential, so that a filter with a large pore size can be used, the processing time of blood can be shortened, and the surface zeta potential can be improved. By treating with a substance that makes the surface zeta potential a positive potential, it can be easily changed and the leukocyte / platelet trapping ability can be changed.

[Brief description of drawings]

FIG. 1 is an example of a leukocyte capture device in which the filter of the present invention is incorporated in a housing.

Claims (1)

[Claims] 1. A leukocyte-removing filter comprising, as a main part, a filter medium composed of a continuous porous body having a positive surface zeta potential and communicating with the outside.