JP3209556B2 - Leukocyte selective removal filter device - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a filter device for selectively capturing and removing leukocytes from a leukocyte suspension.
More specifically, the present invention relates to a filter device for selectively capturing and removing leukocytes mixed in a blood product for transfusion such as whole blood, erythrocyte concentrate, and platelet concentrate.

[0002]

2. Description of the Related Art In recent years, with the advancement of immunology and transfusion, component transfusion has been performed in which only components necessary for treatment of various diseases are concentrated and transfused from conventional whole blood transfusion. . Various blood products used for component transfusion, ie, red blood cell concentrate (CRC), platelet concentrate (PC), and platelet poor plasma (PPP) are separated and fractionated by centrifugation from whole blood obtained by donating blood. Adjusted. However, it has become clear that a large number of leukocytes are contained in the fractionated blood product by centrifugation, and this mixed leukocyte induces post-transfusion side effects.

[0003] Among the side effects after blood transfusion, relatively minor side effects such as headache, non-hemolytic fever reaction, chills, and nausea are caused by reducing the residual ratio of leukocytes contained in blood products to 10 ^-1 to 10 ^-2.
GVH after blood transfusion
D, To prevent serious side effects such as alloantigen sensitization,
Although there is no established theory, it is thought that the survival rate can be almost completely prevented by setting the residual ratio of leukocytes infused by one blood transfusion to 10 ⁻³ to 10 ⁻⁴ or less (“Clinical Studies” 66 (2): 3).
49, 1989).

[0004] Methods for removing leukocytes from blood products include:
Broadly classified, there are two types, a gravity centrifugation method using the difference in specific gravity of blood, and a filter method using a fibrous medium such as a nonwoven fabric or a porous body having continuous pores as a filter medium. The filter method is widely used because of its simplicity and low cost.

[0005]

As it has been found that post-transfusion side effects are induced by leukocytes contaminating blood products for transfusion, high-performance leukocyte removal that removes leukocytes from blood products in high yield. The development of filters has been eagerly desired. It is known that when a fibrous medium such as a nonwoven fabric is used to improve the leukocyte removal ability, it can be achieved by using ultrafine fibers having a smaller fiber diameter or by increasing the packing density of the nonwoven fabric. It is also known that when a porous body having continuous pores is used as a filter medium, it can be achieved by making the pore diameter smaller. However, in any case, with the improvement of the leukocyte removal ability, clogging due to blood cells and microaggregates captured by the filter medium is likely to occur, which may cause problems such as an increase in pressure loss and a prolonged filtration time. Was something.

[0006] Further, since the blood remaining in the filter device after the operation of removing leukocytes is normally discarded together with the filter device, small white blood cells having a small hold-up volume so as to minimize the amount of wastefully discarded blood. There has been a need for a removal filter device. Hold-up volume refers to the internal volume of the filter device. Although the mechanism of leukocyte removal is not yet clear, when a fibrous medium such as a nonwoven fabric is used, it is interpreted as a point at which the fibers are entangled with each other, that is, due to the adhesion at the entanglement point. In order to improve the leukocyte removal ability by increasing the frequency of contact between the leukocytes and the filter medium and increase the size of the filter device, it is necessary to use the ultrafine fibers as described above or increase the packing density of the nonwoven fabric. Then, there is a concern that the pressure loss may increase due to clogging of blood cells and the filtration time may be prolonged.

[0007]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a small and compact leukocyte removal filter apparatus which does not increase pressure loss and has an improved ability to remove leukocytes per unit volume.

Another object of the present invention is to provide a leukocyte selective removal filter device which removes leukocytes from leukocyte suspensions such as whole blood, erythrocyte concentrate, platelet concentrate and platelet poor plasma in high yield.

[0009] The selective leukocyte removal filter apparatus to achieve the above object, a porous body with an average pore size of 3 to 100 [mu] m of continuous pores a filter device filled in a container having an inlet and an outlet of the blood, The average pore diameter of the porous body decreases substantially continuously or stepwise from the blood inlet to the outlet, and the average pore diameter of the porous body on the blood inlet side is 25 to 100 μm , and the blood outlet side is Average pore size is 3 ~
15 μm, and the blood inlet side average pore diameter is the blood outlet side average
It is a leukocyte selective removal filter device characterized by having a pore diameter of 3 to 25 times .

[0010] The present invention also provides an average pore size of 2 to 200 µm.
m, more preferably a filter in which a porous body having continuous pores of 3 to 100 μm is filled in a vessel having an inlet and an outlet for blood, wherein the porous body has an average pore diameter substantially from the blood inlet to the outlet. Fig . 3 shows a leukocyte selective removal filter device which is gradually or continuously reduced .

In the present invention, the average pore diameter refers to a diameter of a porous body having continuous pores cut in a direction perpendicular to the blood flow direction, and the diameter of each of the pores dispersed throughout the cross section is measured. When examining the relationship between and the number of pores, it represents the diameter of the largest number of pores converted to a circle. In other words, the pores dispersed on an arbitrary cut surface of the porous filter have various diameters in various forms, but each pore is converted into a circle having the same area as the cross-sectional area of the pore, and the diameter of the pore is calculated. Is plotted on the abscissa and the number of pores is plotted on the ordinate, generally giving a curve close to a normal distribution. The straight line corresponding to the peak of the curve is the average pore diameter referred to in the present invention.
That is, the average pore diameter is the average diameter of pores dispersed on each of the cut surfaces, and the average pore size on any of the cut surfaces must be in the range of 3 to 100 μm. In addition, the average pore diameter on the blood inlet side and the blood outlet side,
0.5 from the porous material surface to the thickness direction of the filter
mm means the average pore diameter of the cut surface at a portion of not more than 0.1 mm.
If the average pore diameter is not particularly changed within the range of 5 mm in thickness, the average pore diameter on the surface may be used as the average pore diameter on the blood inlet side and the blood outlet side. The average pore diameter was measured using a scanning electron microscope on at least three cut surfaces including the blood inlet and outlet sides, and the diameter of at least 1,000 pores dispersed on the cut surface was measured visually. Then, the average pore diameter at each cut surface is determined, and when the arithmetic mean value of the average pore diameter of each cut surface and the value of the average pore diameter of each cut surface are substantially equal, the porous body has a substantially uniform average pore diameter. A porous body having an average pore diameter on the blood inlet side of 3 to 25 times the average pore diameter on the blood outlet side, and an average pore diameter on the other cut surface less than the average pore diameter on the blood inlet side and greater than the average pore diameter on the blood outlet side. In some cases, the porous body has an average pore diameter decreasing from the blood inlet to the blood outlet.

The continuous or stepwise reduction of the average pore diameter in the present invention means that when one filter material is cut in the blood flow direction, the pore diameter of the porous body gradually increases from the blood inlet to the blood outlet. When it becomes smaller, it is called a continuous decrease.
A case in which several filter materials having a substantially uniform average pore diameter on a cut surface cut perpendicular to the blood flow direction are stacked in order of the average pore diameter and filled into a container is referred to as stepwise reduction.

The filter device for selectively removing leukocytes of the present invention is characterized in that the filter material is arranged so that the average pore diameter of the filter material to be filled decreases continuously or stepwise in the blood flow direction. ing. Improvement of leukocyte removal can be achieved by increasing the packing density of the filter or using a fiber laminate with a smaller average fiber diameter when using a fibrous medium such as a non-woven fabric as the filter material, and by using a porous material having a uniform average pore diameter. For the body, it has been found that this can be achieved by reducing the average pore size.
However, when blood products are filtered using the above filter materials, blood cells are adsorbed to the surface of the filter material over time,
Since the surface of the filter medium is gradually closed, problems such as an increase in pressure loss and an increase in filtration time occur. With respect to such a problem, the use of a porous filter material whose average pore diameter changes substantially continuously or stepwise as in the present invention solves the above problem. That is, when a blood product is treated with the filter device obtained according to the present invention, clogging of blood cells on the filter material surface is reduced because the pore diameter of the filter material near the blood inlet is large, and the blood cells pass along the pore path. This is because, during the passage, leukocytes are gradually adsorbed and captured by the filter material, and pressure loss can be reduced. In addition, when such a filter device is used, most of the filter material volume is efficiently and effectively used for leukocyte capture, so that the leukocyte removal capacity per unit volume is improved, and pressure loss is reduced. In addition, the blood product can be processed in a short time without prolonging the filtration time.

Among blood products for blood transfusion, red blood cell concentrates and whole blood products contain a large amount of red blood cells. Such erythrocyte preparations are more viscous than platelet concentrates and platelet-poor preparations and have a long storage period, so that they often contain many microaggregates and microaggregates. for that reason,
When attempting to capture and remove leukocytes contaminating such red blood cell preparations using a filter, the route through which red blood cells must pass is narrowed due to the high viscosity and adsorption and adhesion of blood cells and microaggregates to the filter material surface. Or, because of the occlusion, the resistance at the time of passage of the red blood cells through the filter is increased, thereby increasing the pressure loss. In order to solve such a problem, the leukocyte removal filter device of the present invention has an effect of suppressing an increase in pressure loss while maintaining good leukocyte trapping ability. That is, since the filter material of the present invention has such a characteristic that its average pore diameter decreases substantially continuously or stepwise from the blood inlet side to the blood outlet side, the blood cells on the filter material surface And clogging of microaggregates is mitigated, and blood cells pass along the pores. Then, during the passage through the filter, leukocytes and microaggregates gradually become adsorbed and captured by the filter material, and the passage through which the red blood cells pass is not extremely narrowed or blocked, so that the pressure is reduced. It is possible to suppress an increase in loss. In addition, since most of the filter material volume is used for capturing leukocytes and microaggregates, the ability to remove leukocytes per unit volume is improved. Further, in order to increase the affinity between blood and the filter material or to further enhance the ability to capture leukocytes, a known surface modification such as graft polymerization or coating of a hydrophilic monomer or polymer on the surface of the filter material ( JP-A-1-249063, JP-A-3-502094
Is even more effective.

When the leukocyte removal filter device of the present invention is used to capture leukocytes mixed in the platelet concentrate and pass platelets, the surface area of the filter material with which blood can come into contact is reduced. There is a need to. That is, if the surface area of the porous body as the filter material is large, the platelets easily come into contact with the filter material, so that the frequency of collision between the filter material and the platelets increases, and the platelet loss increases. In order to deal with such a problem, if the effective surface area of the filter material required to process 1 unit (20 ml) of the platelet concentrate derived from 200 ml of blood collection is 0.10 m ² or less as in the present invention, The frequency of adsorption and adhesion to the cells is reduced, and platelet loss is suppressed. Compared with the same amount of whole blood and erythrocyte concentrate, the platelet concentrate has a red blood cell count of about 1/250 and a white blood cell count of about 1/10, a platelet size of about 1/3 of red blood cells, and a white blood cell count of about 1/3. Because it is as small as about 1/5, it is possible to reduce the effective surface area of the filter material,
In addition, an increase in pressure loss due to clogging of blood cells and microaggregates can be avoided by using the filter device of the present invention, and sufficient leukocyte capturing ability can be maintained. Further, in order to further recover the platelets, it is even more effective if measures such as making the surface properties of the filter material hydrophilic are added. It is believed that the attachment of platelets to the filter material depends on the surface properties of the material. For example, when the material surface is rough or hydrophobic, platelets tend to adhere well to the material surface. On the other hand, it is known that when the material surface is smooth and hydrophilic, the platelet permeability increases. However, in general, the porous polymer is often hydrophobic, and when such a filter material is used, a hydrophilic monomer is graft-polymerized on the material surface, or a hydrophilic polymer is coated on the material surface. A surface modification method such as the above-mentioned method is known as a known material (JP-A-55-1
No. 29755, WO 87/05812, JP-A 1-2
No. 49063). The substantial surface area of the porous body refers to the total surface area of the porous body that can come into contact with blood. The actual surface area is determined by measuring the specific surface area by the mercury intrusion method and multiplying the specific surface area by the density and volume of the porous body.

Hereinafter, the present invention will be described in detail based on embodiments. In the leukocyte selective removal filter device having the above structure according to the present invention, the average pore diameter on the blood inlet side is 10 to 300 μm, and more preferably 20 to 200 μm.
μm, most preferably 25-100 μm. That is, when the average pore diameter is less than 10 μm, during the leukocyte removal operation, blood cells are captured on the surface of the filter material, causing clogging, and there is a fear that pressure loss may increase, while the average pore diameter is more than 300 μm. This is because the frequency of contact between blood cells and the surface of the filter material is reduced, and the capture rate of leukocytes on the surface of the filter material on the blood inlet side is reduced, which may cause clogging of blood cells inside the filter material. It is desirable that the average pore diameter on the blood outlet side is 1 to 30 μm, more preferably 2 to 20 μm, and most preferably 3 to 15 μm. That is, when the average pore diameter is less than 1 μm, the pore path is too narrow, so that clogging of blood cells tends to occur at the blood outlet side, while 30 μm
If the average pore size exceeds m, the trapped amount of leukocytes may be reduced. Further, the average pore diameter on the blood inlet side of the present invention is 2 to 100 times the average pore diameter on the blood outlet side,
More preferably, it is 3 to 50 times, most preferably 3 to 25 times. That is, if the average pore diameter ratio between the blood inlet side and the outlet side is less than twice, clogging with white blood cells may occur, or the amount of captured white blood cells may decrease,
On the other hand, if the pore diameter ratio exceeds 100 times, white blood cells may be clogged on the blood outlet side, and the pressure loss may increase. When the platelet concentrate is treated, the real surface area of the leukocyte selective removal filter material of the present invention is 0.00
1 to 0.10 m ^2, more preferably 0.01 to 0.08 m
² , most preferably 0.02 to 0.06 m ² . That is, if the real surface area is less than 0.001 m ² , the leukocyte trapping amount is too small to be practical, while if the real surface area exceeds 0.10 m ² , the hold-up volume increases, and miniaturization becomes difficult. Because it becomes difficult.

The polymer constituting the filter material for selectively removing leukocytes of the present invention is not particularly limited as long as it does not easily damage blood cells, and various polymers can be used. For example, polyurethane, polyacrylonitrile,
Examples include polyvinyl acetal, polyester, polyamide, polystyrene, polysulfone, cellulose, and cellulose acetate. Further, the filter material of the present invention may be manufactured by a known manufacturing method. It is also preferable to perform a known surface modification on the filter to enhance the ability to capture leukocytes.

[0018]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the filter device for selectively removing leukocytes according to the present invention will be described in detail with reference to embodiments.

[0019]

Example 1 The polymer material was made of cellulose, the average pore size on the blood inlet side was 50 μm, and the average pore size on the blood outlet side was 8
A μm porous body was filled in a container having an effective cross-sectional area of 30 × 30 mm.

Erythrocyte concentrate 2 fractionated by centrifugation
00 cc (14-16 days of stored blood) was filtered at a constant flow rate of 4.5 ml / min using a blood circuit incorporating the above filter device. The filtration is terminated when the blood in the blood bag is exhausted and the blood flow substantially stops.
7.3 cc of filtrate was obtained. The hematocrit value was measured as the volume of the red blood cell concentrate (hematocrit value 67%) and the filtrate before filtration, the leukocyte concentration and the red blood cell concentration, and the leukocyte removal rate and the red blood cell recovery rate were calculated according to the following equations (1) and (2). Leukocyte removal rate is 99.8%, red blood cell recovery rate is 9
It was 4.5%.

[0021]

(Equation 1)

[0022]

(Equation 2)

The volumes of the pre-filtration liquid and the filtrate were determined by dividing each weight by a specific gravity of 1.075. The measurement of leukocyte concentration was performed by the following method. Before filtration liquid: by Turk was poured filtered before solution diluted 10 times in a hemocytometer Barker Turk type, count the white blood cells present in the large compartment 4 in the compartment using an optical microscope, the value n _pre And Leukocyte concentration (before filtration) = _npre x 0.25 x 10 ⁵ cells / ml

Filtrate: hemolyzed (1.14 in 100 μl of filtrate)
200 μl of 5% ammonium oxalate physiological saline) and a fluorescent staining solution (69.9 mg / 1 acridine orange solution)
After adding 30 μl and stirring, the solution was injected into 1 to 3 Barker-Turck-type hemacytometers, and the white blood cells present in the large compartments 4 to 54 were counted using an epi-illumination fluorescence microscope. The value was n _post . The leukocyte concentration of the filtrate was determined by the following equation (3).

[0025]

(Equation 3) The pressure loss at the time of blood filtration was 50 mmHg.

[0026]

COMPARATIVE EXAMPLE 1 An experiment was conducted under the same conditions as in Example 1 for a porous body composed of polyvinyl formal as a polymer material and having a uniform average pore diameter of 50 μm. As a result, the leukocyte removal rate was 55.3%, the red blood cell recovery rate was 96.2%, and the pressure loss was 22 mmHg.

[0027]

Comparative Example 2 A porous material having a uniform average pore diameter of 8 μm in which the polymer material was polyvinyl formal was used in Example 1.
An experiment was performed under the same conditions as described above. As a result, clogging occurred due to blood cells and microaggregates, and only 124 cc was collected. The leukocyte removal rate was 99.8%, the red blood cell recovery rate was 89.0%, and the pressure loss was 500 mmHg or more.

[0028]

Comparative Example 3 An experiment was conducted under the same conditions as in Example 1 for a porous body having a polymer material made of cellulose and having an average pore diameter of 300 μm on the blood inlet side and an average pore diameter of 2 μm on the blood outlet side. As a result, clogging was caused by blood cells and microaggregates, and only 78 cc was collected. Leukocyte removal rate is 98.6%, red blood cell recovery rate is 67.3%, and pressure loss is 500.
mmHg or more.

[0029]

Comparative Example 4 An experiment was carried out under the same conditions as in Example 1 for a porous body composed of cellulose as the polymer material and having an average pore diameter of 500 μm on the blood inlet side and an average pore diameter of 8 μm on the blood outlet side. As a result, the leukocyte removal rate was 98.2%, the red blood cell recovery rate was 84.5%, and the pressure loss was 380 mmHg or more.

[0030]

[Table 1]

Table 1 shows the types of porous bodies used, the average pore diameter, the ratio of the average pore diameter on the blood inlet side to the outlet side (pore diameter ratio), and the leukocyte removal rate (%) for Example 1 and Comparative Examples 1 to 4. ,
Shows red blood cell recovery (%) and pressure loss. As the performance of a filter that captures white blood cells from a red blood cell preparation and allows red blood cells to pass, a leukocyte removal rate of 90% or more and a red blood cell recovery rate of 85% or more are practically necessary. Further, it is preferable that the filtration time is short, so that the pressure loss is preferably within 200 mmHg.

When a porous material having a uniform average pore size (pore size ratio = 1) is used as a filter material, the leukocyte removal rate is low (Comparative Example 1) or clogging with blood cells occurs, increasing pressure loss ( Comparative Example 2) There is a tendency. Further, when the average pore diameter on the blood outlet side is small and the average pore diameter on the inlet side is large, that is, when the pore diameter ratio exceeds 100, blood cell clogging on the blood outlet side tends to increase and the pressure loss tends to increase (Comparative Example). 3). Further, when the average pore diameter on the blood inlet side exceeds 300 μm, the ability to capture leukocytes on the blood inlet side decreases,
As a result, a decrease in the leukocyte removal rate and an increase in pressure loss due to clogging at the blood outlet side are observed (Comparative Example 4). On the other hand, when the filter material of the present invention shown in Example 1 was used, it was found that the white blood cell removal rate and the red blood cell recovery rate were good and the pressure loss was low.

[0033]

Example 2 A filter material composed of polyurethane as a polymer material and having uniform average pore diameters of 30 μm and 8 μm was laminated, and filled in a container having an effective filtration area of 43 × 43 mm. At this time, the filter thickness was 2 mm, and the surface area of the filter material was 0.98 m ² .

Platelet concentrate 2 fractionated by centrifugation
0 units (460 cc) were filtered at a 1.5 m drop at a flow rate of 5 g / min using a blood circuit incorporating the above filter device. The end of the filtration is defined as a point in time when the blood in the blood bag is exhausted and the flow of the blood substantially stops.
The filtrate of c was obtained. The volume, platelet concentration, and leukocyte concentration of the platelet concentrate and the filtrate before filtration were measured, and the leukocyte removal rate and the platelet recovery rate were determined according to Equations 1 and 4, and the leukocyte removal rate was 99.9%. Recovery rate of 91
%, And the pressure loss was 26 mmHg.

[0035]

(Equation 4)

The leukocyte concentration before filtration was determined by diluting 10 times with the Turk's solution and then observing by optical microscopy. The leukocyte concentration after filtration was measured by adding acridine orange, and diluting the sample by 1.1 times with a fluorescence microscope. The number was counted and determined. The platelet concentration was determined by measuring a sample diluted 250,000 times with an automatic blood cell counter. Also, 200
The substantial surface area of the porous body treated with 1 unit of the concentrated platelet solution derived from ml blood collection was 0.049 m ² .

[0037]

Comparative Example 5 A porous material having a uniform average pore diameter of 8 μm was filled in a container having an effective filtration area of 21.5 × 21.5 mm. At this time, the filter thickness was 1 mm, and the surface area of the filter material was 0.14 m ² .

Platelet concentrate 3 fractionated by centrifugation
When the unit (60 cc) was treated in the same blood circuit as in Example 2, clogging occurred and only 20 cc of filtrate was collected. According to Equations 1 and 4, the leukocyte removal rate,
When the platelet recovery rate was determined, the leukocyte removal rate was 9%.
8.8%, platelet recovery rate 11%, pressure loss 425m
mHg. In addition, the substantial surface area of the porous body treated with 1 unit of the concentrated platelet solution derived from 200 ml of blood was 0.04.
7 m ² .

[0039]

Comparative Example 6 A porous material having a uniform average pore diameter of 8 μm was used as a comparative example.
And filled in the same container. A polymer (HEMA: D) composed of 2-hydroxyethyl methacrylate (HEMA) and dimethylaminoethyl methacrylate (DM)
M = 97: 3, abbreviated as HM-3) in 1% ethanol solution, nitrogen was flowed at a flow rate of 21 / min for 20 minutes to remove excess polymer liquid, and the container after coating was further coated at 40 ° C. for 15 hours. Vacuum dried.

Comparative Example 5
3 units (60 cc) of a 200 ml blood-collected platelet concentrate were treated in the same manner as described above, and the leukocyte removal rate and platelet recovery rate were determined. The leukocyte removal rate was 99.7% and the platelet recovery rate was 65.0%. Met. Further, the pressure loss is 278.
mmHg, and the real surface area of the porous body treated with 1 unit of 200 ml blood-collected platelet concentrate was 0.047 m ² .

[0041]

[0042]

COMPARATIVE EXAMPLE 7 A polymer material comprising cellulose, a filter material having a uniform average pore diameter of 250 μm and 2 μm was laminated, and HM-3 polymer was coated in the same manner as in Comparative Example 6. Blood circuit similar to 6 and 2
When 3 units of the platelet concentrate from 00 ml of blood was treated, clogging occurred and only 37 cc could be collected. When the leukocyte removal rate and the platelet recovery rate were determined, the leukocyte removal rate was 98.6% and the platelet recovery rate was 23.4%. In addition, the pressure loss was 389 mmHg, and the substantial surface area of the porous body treated with 1 unit of 200 ml of blood-collected platelet concentrate was 0.034 m ² .

[0043]

Example 3 A polymer material made of polyvinyl formal, filter materials having uniform average pore diameters of 50 μm, 30 μm and 8 μm were laminated, and HM-3 polymer was coated in the same manner as in Comparative Example 6, and then compared. The same blood circuit as in Examples 5 to 7 was used to treat 3 units of 200 ml blood-derived platelet concentrate to determine the leukocyte removal rate and platelet recovery rate. The leukocyte removal rate was 99.6%, and the platelet recovery rate was 93.
2%. Further, the pressure loss is 20 mmHg,
The substantial surface area of the porous body treated with 1 unit of 200 ml of blood-derived platelet concentrate was 0.062 m ² .

[0044]

[Table 2] PU: polyurethane PVF: polyvinyl formal Pore size ratio = Average pore size on the blood inlet side / Average pore size on the blood outlet side

Table 2 shows, for Examples 2 and 3 and Comparative Examples 5 to 7 , the type of porous material used, the average pore size, the ratio of the average pore size on the blood inlet side to the outlet side (pore size ratio), and the HM-3 coating. Presence, leukocyte removal rate (%), platelet collection rate (%),
2 shows the surface area and pressure loss of a porous body when one unit of a 200 ml blood-collected platelet concentrate was treated.

As a filter that captures leukocytes from a platelet concentrate and allows platelets to pass through, a leukocyte removal rate of 90% or more and a platelet recovery rate of 85% or more are practically necessary. Further, it is preferable that the filtration time is short, so that the pressure loss is preferably within 200 mmHg.

Comparative Examples 5 and 6 are filter devices filled with a porous material having a uniform average pore diameter of 8 μm. The filter device has a tendency to cause clogging on the surface of the filter material, and has a high pressure loss. HM with high hydrophilicity for the purpose of suppressing platelet adhesion to platelets and enhancing platelet permeability
The filter of Comparative Example 6 coated with -3 polymer has a lower pressure loss than the filter of Comparative Example 5, but still has a higher platelet loss. By coating the HM-3 polymer, the surface of the material is hydrophilized and the permeability of blood cells is increased. However, the average pore diameter of the used porous material is uniform at 8 μm, which is not enough to suppress the adhesion of leukocytes and microaggregates on the surface of the filter material. platelets are narrowed to be hole path passes, or platelet recovery rate to be closed is reduced, it is thought to be higher pressure loss. In Comparative Example 7, the ratio of the average pore diameter on the blood inlet side to the average pore diameter on the blood outlet side was 1
This is an example in which clogging of blood cells on the blood outlet side is induced because of being as large as 25.

[0048]

The filter device for selectively removing leukocytes according to the present invention comprises a porous material filled in a container having an inlet and an outlet for blood.
The average pore size of the body, the average pore size on the blood entry side, and the flatness on the blood exit side.
Hitoshiana diameter, the inlet-side average pore size / outlet average pore size respectively top
Is also a preferred range, 3 to 100 μm, 25 to 100
μm, 3 to 15 μm, 2 to 25 times, and the average pore diameter of the porous body decreases substantially continuously or stepwise from the inlet to the outlet of blood. Because of the feature, the leukocyte removal ability per unit volume can be increased without increasing the pressure loss, and the size can be reduced.

Continuation of the front page (56) References JP-A-3-173825 (JP, A) JP-A-54-66589 (JP, A) JP-A-64-7514 (JP, A) , A) (58) Field surveyed (Int. Cl. ⁷ , DB name) A61M 1/02 A61M 1/34 B01D 15/08

Claims (1)

(57) [Claims] 1. A filter device in which a porous body having continuous pores having an average pore diameter of 3 to 100 μm is filled in a vessel having an inlet and an outlet for blood, wherein the porous body is moved from the inlet to the outlet of the blood. Is substantially continuously or stepwise reduced, and the average pore diameter of the porous body on the blood inlet side is 25 to 100 μm , and the average pore diameter on the blood outlet side is 3 to
15 μm, and the blood inlet side average pore diameter is the blood outlet side average
A selective leukocyte removal filter device having a pore diameter of 3 to 25 times .