JP2559615B2 - Leukocyte capture filter for concentrated red blood cells - Google Patents

Description

TECHNICAL FIELD The present invention relates to a filter for selectively capturing leukocytes and microaggregates from concentrated red blood cells obtained from blood, body fluid and the like.

More specifically, concentrated red blood cells obtained by subjecting body fluids containing blood cells such as blood, bone marrow fluid, and lymph fluid to some treatment, such as citrate-phosphate-glucose (citrate).
-Phosphate-dextrose (hereinafter abbreviated as CPD)), concentrated red blood cells obtained by centrifuging anticoagulated whole blood and removing supernatant plasma, and concentrated red blood cells obtained by adding adenine, mannitol, sorbitol, guanosine, physiological saline, etc. to the concentrated red blood cells. The present invention relates to a filter for selectively capturing leukocytes and microaggregates from a suspension or the like.

In recent years, due to advances in medical science such as hematology and immunology, component transfusion in which red blood cells, platelets, plasma, etc. are separated from whole blood and transfused to treat various diseases has become widespread. Such blood component transfusion has advantages over conventional whole blood transfusions in that unnecessary components can be removed and only necessary components can be transfused to a patient, and blood can be effectively used. Used for treatment in hospitals. However, it is known that other than blood transfusion or component transfusion, other blood components mixed in blood for transfusion, particularly white blood cells and microaggregates, cause undesired transfusion side effects for transfused patients. That is, leukocyte antigens are present on the surface of leukocytes, and there are various types of this leukocyte antigen depending on the person, and very few persons have the same leukocyte antigen. Therefore, an anti-leukocyte antibody is produced in the body of a patient who has been transfused with the white blood cells of another person. As a result, in the case of a patient who is frequently transfused, the leukocytes of another person who has been transfused and the anti-leukocyte antibody in the patient's blood cause an antigen-antibody reaction, which causes transfusion side effects such as urticaria and fever. Further, the microaggregates are aggregates of platelets and white blood cells. If the microaggregates are present in the transfused blood, the microaggregates are clogged with the microvessels of the transfused patient to cause embolism. Therefore, it is desirable to remove leukocytes and microaggregates present in the blood components to be transfused. In addition, since leukocyte antigens are also present on the surface of platelets, it is preferable to remove platelets except in the case of platelet transfusion.

(Prior Art) A conventional technique capable of removing leukocytes and microaggregates from transfused blood is a method of adding a frost damage protection liquid to freeze blood and then removing the frost damage protection liquid by washing. A method of centrifuging whole blood to remove buffy coat and / or plasma. A method of removing fine aggregates by filtration. There is a method of removing microaggregates and white blood cells by filtration.

In this method, whole blood is collected using CPD as an anticoagulant, and then concentrated red blood cells are added, and a frost damage protection solution is added to freeze the blood. This is a method in which, after thawing, the frost damage protection liquid is removed by washing to give a red blood cell suspension. Although this method is a good method with very few leukocytes mixed in, it requires a great deal of labor and an expensive device, so that it is generally not widely used and limited to special applications.

Is a method of centrifuging CPD-supplemented blood, removing buffy coat and plasma, and washing by decantation several times. With this method, the leukocyte removal rate cannot be increased so high that the immune reaction during transfusion cannot be completely suppressed. In addition, this is a labor-intensive method.

The above method is a method of removing microaggregates from blood by a filter using a fiber lump or a net. This method basically cannot remove unaggregated leukocytes, and thus cannot prevent transfusion side effects due to leukocytes.

The method (1) is a method in which blood is filtered through a filter using ultrafine fibers to remove most of microaggregates, leukocytes and platelets in blood. This method is a technique that has started to spread widely in recent years because it can efficiently capture leukocytes, microaggregates, and even platelets and is easy to operate.
The only drawback is that the distribution of the size and amount of micro-aggregates generated in the blood is very different depending on the storage condition of the blood, especially in the case of concentrated red blood cells, the viscosity is also large,
Since the amount of micro-aggregate is large, the filter is likely to be clogged. In order to prevent this, in addition to the main filter made of ultrafine fibers, an attempt has been made to prevent clogging by providing a coarse filter and removing large agglomerates. It is not technically complete enough to handle stored blood.

(Problems to be Solved by the Invention) An object of the present invention is to remove white blood cells and microaggregates from blood, particularly concentrated red blood cells, focusing on the above-mentioned problems of the filter using ultrafine fibers. Therefore, it is to provide a filter that does not cause clogging of the filter regardless of the storage state of concentrated red blood cells, and to provide a filter that can efficiently remove leukocytes and microaggregates in a short time.

(Means for Solving Problems) The present inventors have solved the above problems and can filter blood, particularly concentrated red blood cells in a short time, and efficiently remove leukocytes and microaggregates from blood. The research was conducted intensively for the purpose of providing a filter. As a result, the leukocyte-capturing filter material A composed of ultrafine fibers, that is, the average fiber diameter is X (μ
m), and the average interfiber spacing is Y (μm), 7XY
And a filter medium B having an average fiber diameter and / or an average interfiber spacing slightly larger than that, that is,
Filter medium B satisfying 50XY> 7, and filter medium C having a larger average fiber diameter and / or average interfiber spacing than filter medium B, that is, filter medium C satisfying XY> 50 Even with red blood cells, that is, regardless of the size and distribution of the micro-aggregates generated in the blood, a stable filtration rate was always obtained. It was found that a high filtration rate can be obtained, and the present invention was obtained.

That is, the present invention relates to a leukocyte separation filter comprising a filter medium made of a fibrous substance filled in at least one container having at least one blood inlet and at least one blood outlet, and having an average fiber of the fibrous substance. When the diameter is X (μm) and the average inter-fiber spacing defined by the following formula (1) is Y (μm), at least three types of filter media A,
B, C, filter material A is 7XY, filter material B is 50XY> 7,
The filter medium C satisfies XY> 50, and further, the filter medium is arranged in the order of C, B, and A from the blood inlet to the blood outlet, in order to collect leukocytes for concentrated red blood cells.

Where Y is the average interfiber spacing (μm), X is the average fiber diameter (μm), ρ is the density of the fibrous material (g / cm ³ ), D is the bulk density of the filter medium (g / cm ³ ), and π is It is the pi.

The term “fibrous substance” as used in the present invention refers to a substance in which the length of the fibrous substance is sufficiently longer than the average diameter of the fibrous substance. Any material can be used as long as it can maintain a fibrous form such as synthetic fiber, semi-synthetic fiber, natural fiber, regenerated fiber, metal fiber, and mineral fiber, but polyester, polypropylene whose diameter and length are easily controlled, Synthetic fibers such as polyamide, polyacrylonitrile and cellulose acetate are preferably used. Among synthetic fibers, polyester, polypropylene, etc. are easy to make ultrafine fibers. The filter medium referred to in the present invention refers to a cotton-like aggregate of a fibrous substance, a non-woven fabric-like aggregate, a woven fabric-like aggregate, a network structure, etc. Among them, the non-woven fabric is easy to handle, the uniformity of the flow of concentrated red blood cells, It is excellent in processing speed, leukocyte, and micro-aggregate trapping performance, and it is preferably used. The container referred to in the present invention has a structure in which blood does not leak, has a blood inlet for introducing blood and a blood outlet for discharging blood, and the concentrated red blood cells introduced from the blood inlet serve as a filter medium. Any structure or material may be used as long as it has a structure through which it can be guided to the blood outlet. Further, the filter medium is not necessarily one container, and the filter medium may be stored in some containers in a dispersed manner. The average fiber diameter of the fibrous material referred to in the present invention means the diameter when the cross-sectional area of the cross section of the fiber perpendicular to the longitudinal direction is converted into a true circle of the same area, and when there is a distribution in the diameter, Say that arithmetic mean.
The average inter-fiber spacing is a fiber in a model in which fibrous substances of the same diameter are aligned in the length direction of the fiber and packed in a container, and the distance between all adjacent fibers is the same. Is the distance between adjacent fibers and is defined by the following equation (1).

Where Y is the average interfiber spacing (μm), X is the average fiber diameter (μm), ρ is the density of the fibrous material (g / cm ³ ), D is the bulk density of the filter medium (g / cm ³ ), and π is It is the pi.

In the present invention, at least three types of filter media made of fibrous substances are required. One filter medium A is 7 when the average fiber diameter is X (μm) and the average interfiber spacing is Y (μm).
It must satisfy the XY formula. The filter medium A corresponds to a filter made of ultrafine fibers, and is a filter capable of efficiently capturing leukocytes in concentrated red blood cells, particularly all leukocytes including lymphocytes which are considered to be difficult to capture.

The second filter medium B must satisfy the formula of 50XY> 7. The filter medium B is a filter having a slightly larger average fiber diameter and / or average interfiber spacing than the filter medium A, and is a filter for capturing relatively small microaggregates slightly larger than white blood cells. The last filter medium C must satisfy the formula of XY> 50. The filter medium C is a filter having a larger average fiber diameter and / or average inter-fiber spacing than the filter medium B, and is a filter for trapping large microaggregates that may clog the filter medium B. is there.

Here, the range of XY of the filter medium A is the ease of manufacturing the fiber,
The range of 7 xy 0.3 is more preferable in view of prevention of clogging of red blood cells and ease of maintaining the average inter-fiber spacing when passing concentrated red blood cells. More preferable is 7XY0.5, and 7XY0.8 is the most preferable. In addition, XY of filter medium C
The range of 150000XY>
A range of 50 is more preferable. More preferable is 100000XY
> 50, and 80,000XY> 50 is the most desirable.

Since the white blood cell concentration in the concentrated red blood cells is very high, the XY of the filter medium A must be 7 or less in order to efficiently capture the white blood cells therein. When XY of the filter medium A is larger than 7, leukocytes including lymphocytes which are difficult to adhere to the filter medium A cannot be efficiently captured. Further, in order to prevent the filter medium A from being clogged with a large amount of microaggregates contained in concentrated red blood cells, the filter mediums B and C are indispensable, and the filter medium B for removing the particularly small microaggregates is the filter medium C. It is important to use in combination with. Since the filter medium A is a filter made of very fine fibers, it has a very high ability to capture microaggregates and leukocytes. However, since this filter medium A is apt to be clogged by the microaggregates generated in the preserved blood, it needs to be combined with a filter for removing the microaggregates. The filter for removing micro-aggregates conventionally used for such a purpose does not have sufficient ability to remove micro-aggregates, and the filter medium A is often clogged due to the difference in the preservation state of blood. What has heretofore been known as a microaggregate removing filter to be used in combination with the filter medium A is a combination of filter media corresponding to the filter medium C referred to in the present invention, or a single microaggregate removing filter (Japanese Patent Application Laid-Open No. S60-18753). 60-203267). When such a filter is combined with the filter medium A, the filter medium A can be used for some blood.
It is possible to prevent clogging of the. However, such a clogging prevention effect is not exerted on all blood, and even if it is possible to prevent complete clogging and blood flow, the time required to process blood is still low. It took a long time. This is particularly remarkable when concentrated red blood cells, that is, whole blood, is centrifuged and red blood cell concentrated liquid in which supernatant plasma is removed is used, and is more remarkable when stored blood of concentrated red blood cells is used. That is, when the filter disclosed in JP-A-60-203267 is used for concentrated red blood cells, the filter is clogged by a large amount of microaggregates contained in the concentrated red blood cells, which is necessary for treating the concentrated red blood cells. It took a very long time.

On the other hand, the combination of the present invention, that is, the filter medium A
On the other hand, the filter in which filter medium B and filter medium C are combined has a surprisingly great effect of preventing clogging against concentrated red blood cells in any storage condition, and the time required for treating the concentrated red blood cells is significantly increased. It becomes short. The reason for this is considered as follows. That is, there are various kinds of micro-aggregates generated in concentrated red blood cells in large and small sizes, and among them, small ones as small as white blood cells to large ones observable with the naked eye are generated. A conventional commercially available filter for removing microaggregates, that is, a combination of filters corresponding to the filter medium C of the present invention can remove large microaggregates, but microaggregates that are as large as or slightly larger than white blood cells. Cannot be completely removed, and these fine aggregates pass through the fine aggregate removal filter and are sent to the filter medium A, so that the filter medium A is clogged. In the filter medium A, leukocytes are dispersed and captured in the depth direction of the filter medium A, and the filter medium A functions as a so-called depth filter. However, since the micro-aggregates have high adhesiveness and also include those slightly larger in size than white blood cells, they are captured at a high density on the surface of the filter medium A, resulting in clogging of the filter medium A. Will end up.
Also, in the case of the microaggregate filtration filter alone corresponding to the filter medium B in the present invention, this microaggregate removal filter functions as a so-called depth filter for small microaggregates, and the depth of the filter medium B is increased. Although it is possible to disperse in the vertical direction to capture the microaggregates, large microaggregates are trapped only on the surface of the microaggregate removal filter, and the microaggregate removal filter itself becomes clogged.

In the leukocyte-trapping filter of the present invention, that is, in the combination of the filter medium A, the filter medium B and the filter medium C, as compared with such a conventional filter, large fine aggregates are dispersed near the surface of the filter medium C or captured in the depth direction, Only small micro-aggregates and white blood cells are sent to the filter medium B. In the filter medium B, small micro-aggregates are dispersed and captured in the depth direction of the filter medium B, and only white blood cells and a few micro-aggregates of the same size as white blood cells are sent to the filter medium A. As a result, even in the filter medium A, these white blood cells and micro-aggregates of the same size as the white blood cells are dispersed and captured in the depth direction of the filter medium A, so that the filter medium A is not clogged. That is, the filter medium A
In both the filter medium B and the filter medium C, white blood cells and micro-aggregates are dispersed and captured in the depth direction of the filter medium, so that a blood channel can be secured in the filter medium, clogging can be prevented, and blood is treated. It is presumed that the time required for the operation will be shortened sufficiently.

The combination of Filter A, Filter B, Filter D and Filter E gives more favorable results when the blood contains more microaggregates.

Here, when the average fiber diameter is X (μm) and the average inter-fiber spacing is Y (μm), the filter medium D satisfies 1100XY> 50, and the filter medium E satisfies XY> 1100.

The filter media A, B, C, D and E described above are C, B, A; E, D, B, A having an average fiber diameter and / or an average interfiber distance from the blood inlet to the blood outlet. They are arranged in the order of increasing distance. Each of the filter materials A, B, C, D, and E may be one type, but not one type, and several types of filter materials may be combined. In addition, a spacer may or may not be provided between the respective filter media. Further, even if the order of the filter media A, B, C, D, E is changed, that is, E, D, E ', B, D', A, etc., E'and D'are effectively blood flow channels. The present invention also includes such a combination because it does not have any adverse effect on the clogging.
Further, for example, putting the filter medium A only in a part of the blood flow path in front of the filter medium B in the cross-sectional direction or putting the very thin filter medium A in front of the filter medium B almost causes clogging of the blood flow channel. The present invention also includes such combinations as they have no effect.

 Hereinafter, the present invention will be described in more detail with reference to the drawings.

FIG. 1 is a schematic sectional view showing an example of the constitution of the leukocyte capture filter of the present invention. The container 1 has a blood inlet port 2 and a blood outlet port 3, and a filter material A4, a filter material B5 and a filter material C6 made of a fibrous substance are stored in the container 1, and the filter material A,
B and C are clamped by the container 1 at their ends 7 and 8 in order to prevent blood from leaking.

As described above, when the average fiber diameter is X (μm) and the average interfiber spacing is Y (μm), the filter medium A is 7XY and the filter medium B is
50XY> 7, and the filter medium C satisfies XY> 50. The concentrated red blood cells are introduced into the container 1 through the blood inlet 2 and first introduced into the filter medium C6, where large microaggregates in blood are removed, and blood containing small microaggregates and white blood cells is filtered through the filter medium.
Sent to B5. In the filter medium B5, small micro-aggregates are removed, and the blood from which the micro-aggregates have been removed is then sent to the filter medium A4, where white blood cells are captured. The blood from which the microaggregates and white blood cells have been removed is led out from the blood outlet 3. Since almost no micro-aggregates are sent to the filter material A4, this filter material A4
The blood is processed in a short time because there is no clogging in the filter media B5 and C6.
Further, the blood obtained from the blood outlet 3 contains almost no microaggregates and white blood cells.

(Example) Hereinafter, the present invention will be described in more detail with reference to Examples.

(Example 1 and Comparative Examples 1 to 3) In Example 1, as a white blood cell trapping filter, a filter medium A having the composition shown in Table 1 was placed in a container having a structure shown in the accompanying drawings.
B, C from the blood inlet to the blood outlet, C, B,
What was laminated in the order of A was used. The cross-sectional area of the part where blood actually passes in the container is 45 cm ² (6.7 cm x 6.7 cm), the container is made of acrylic styrene resin, the filter material is polyester non-woven fabric, and the filter material A has an average fiber diameter X. Is 1.
65 μm, average inter-fiber spacing Y of 3.1 μm, and non-woven fabrics with a thickness of 5.3 mm were used. XY of filter material A is 5.1
Met. As the filter material B, one having an average fiber diameter X of 4 μm, an average interfiber spacing Y of 6.6 μm and a thickness of 2.5 mm obtained by superposing non-woven fabrics was used. The XY of the filter medium B was 26.4. As the filter medium C, the average fiber diameter X is 25 μm, the average inter-fiber spacing Y is 40 μm, and the thickness of non-woven fabrics is 2.5 m.
I used m. The XY of the filter medium C was 1000.

Comparative Example 1 does not use the filter medium C in Example 1, Comparative Example 2 does not use the filter medium B in Example 1, and Comparative Example 3 uses the leukocyte-removing filter manufactured by A company. I was there. Comparative Examples 1, 2 and 3 are disclosed in
It corresponds to the filter disclosed in 60-203267. In the constitution of the leukocyte removal filter manufactured by Company A, the filter medium A is the same as that in Example 1, the filter medium B is not provided, and three types of filter medium are used as the filter medium C. The filter material C1 has an average fiber diameter X of 13.8 μm,
The average inter-fiber spacing Y is 17.2 μm, XY is 237, and the thickness of laminated non-woven fabrics is 1.7 mm. The filter medium C2 has an average fiber diameter X.
Is 13.7 μm, average inter-fiber spacing Y is 24.7 μm, XY is 338,
The thickness of laminated non-woven fabrics is 1.1 mm, the filter medium C3 has an average fiber diameter X of 31.5 μm, and an average interfiber spacing Y of 32.4 μm.
m, XY was 1021, and the thickness of the laminated non-woven fabrics was 2.2 mm. These filter media were laminated in the order of C3, C2, C1, and A from the blood inlet to the blood outlet, and the cross-sectional area of the portion through which blood passed and the material of the container and the non-woven fabric were the same as in Example 1. Met.

CPD-added human concentrated red blood cells (type A blood pooled, stored at 4 ° C for 14 days, white blood cells 12100 / mm ³ , hematocrit (Ht) 75%, platelets 15 × 10 ⁴ / mm ³ With a drop of 150 cm, Example 1 and Comparative Examples 1, 2, 3
500 ml was applied to each of the filters. After the blood flow was completed, the red blood cells in the filter were washed with 50 ml of physiological saline. Filtration time is the time from the start of flowing blood to the end of flowing physiological saline is measured by a stopwatch, and the leukocyte removal rate is the blood used in the experiment after measuring the leukocyte concentration with a calculation plate by Turk staining. Compared to the total amount of white blood cells in the formula {1- (leaked white blood cells) / (total white blood cells)}
The platelet removal rate was calculated from × 100, and the platelet concentration was measured by the Brecker-Kronkite method, and then compared with the total amount of blood platelets used in the experiment to obtain the expression {1- (leaked platelets) /
(Total platelets)} × 100, and the red blood cell recovery rate was calculated from the formula {(leakage bleeding Ht) (leakage blood amount) / (used blood Ht) (used blood amount)} × 100 by measuring hematocrit. Table 2 shows the results.

From Table 2, in comparison with Comparative Examples 1, 2 and 3 corresponding to the filter disclosed in JP-A-60-203267, in Example 1, the filter medium A was used.
By combining filter medium B and filter medium C, the leukocyte removal rate, platelet removal rate, and erythrocyte recovery rate are sufficiently high, although the time required for treating concentrated red blood cells (filtration time) is significantly shortened. It is clear that it has performance. That is, in the case of filtering concentrated red blood cells with a filter, with the filter disclosed in JP-A-60-203267, when the filter of the present invention is used, the filtration time is significantly extended compared to whole blood. It can be seen that the filtration time is significantly shortened.

(Example 2) As Example 2, filter media A, B, and C having the compositions shown in Table 3 were laminated in the same container as Example 1 in the order of C, B, and A from the blood inlet port toward the blood outlet port. I used one. A non-woven fabric of polyester was used as the filter medium.

CPD-added human concentrated red blood cells (type A blood pooled, stored at 4 ° C for 10 days, white blood cells 12500 / mm ³ , hematocrit (Ht) 73%, platelets 18 × 10 ⁴ / mm ³ Was poured into the filter of Example 2 with a drop of 150 cm. After the blood flow was completed, the red blood cells in the filter were washed with 50 ml of physiological saline. The filtration time, leukocyte removal rate, platelet removal rate and red blood cell recovery rate were measured and calculated in the same manner as in Example 1. The results are shown in Table 4.

From Table 4, in Example 2, by using the filter in which the filter media A, B and C are combined, the time required for treating the concentrated red blood cells (filtration time) is very short, the leukocyte removal rate, the platelet removal rate, It can be seen that the red blood cell recovery rate is good.

(Example 3) As Example 3, filter media A, B, and C having the compositions shown in Table 5 were laminated in the same container as Example 1 in the order of C, B, and A from the blood inlet to the blood outlet. I used one. A non-woven fabric of polyester was used as the filter medium.

CPD-added human concentrated red blood cells (type A blood pooled, stored at 4 ° C for 1 day, white blood cells 13200 / mm ³ , hematocrit (Ht) 71%, platelets 24 × 10 ⁴ / mm ³ Was poured into the filter of Example 3 with a drop of 150 cm. After the blood flow was completed, the red blood cells in the filter were washed with 50 ml of physiological saline. The filtration time, leukocyte removal rate, platelet removal rate and red blood cell recovery rate were measured and calculated in the same manner as in Example 1. The results are shown in Table 6.

From Table 6, in Example 3, by using the filter in which the filter media A, B and C are combined, the time required for treating the concentrated red blood cells (filtration time) is very short, the leukocyte removal rate, the platelet removal rate, It can be seen that the red blood cell recovery rate is good.

(Example 4) As Example 4, filter media A, B, C1, and C2 having the compositions shown in Table 7 were placed in the same container as that of Example 1 from the blood inlet to the blood outlet, C2, C1, B, and A. Was used in this order. A non-woven fabric of polyester was used as the filter medium.

CPD-added human concentrated red blood cells (type A blood pooled, stored at 4 ° C for 5 days, white blood cells 11100 / mm ³ , hematocrit (Ht) 73%, platelets 17 × 10 ⁴ / mm ³ Was dropped on the filter of Example 4 at a drop of 150 cm. After the blood flow was completed, the red blood cells in the filter were washed with 50 ml of physiological saline. The filtration time, leukocyte removal rate, platelet removal rate and red blood cell recovery rate were measured and calculated in the same manner as in Example 1. The results are shown in Table 8.

From Table 8, in Example 4, by using the filter in which the filter media A, B, C1 and C2 are combined, the time required for treating the concentrated red blood cells (filtration time) is very short, the leukocyte removal rate, and the platelet removal. It can be seen that both the rate and the red blood cell recovery rate are good.

(Example 5) As Example 5, filter media A, B, C1, and C2 having the compositions shown in Table 9 were placed in the same container as that of Example 1 from the blood inlet port toward the blood outlet port C2, C1, B, and A. Was used in this order. As the filter material, a polyamide non-woven fabric was used.

CPD-added human concentrated red blood cells (type A blood pooled, stored at 4 ° C for 21 days, white blood cells 11400 / mm ³ , hematocrit (Ht) 70%, platelets 14 × 10 ⁴ / mm ³ Was dropped on the filter of Example 5 at a drop of 150 cm. After the blood flow was completed, the red blood cells in the filter were washed with 50 ml of physiological saline. The filtration time, leukocyte removal rate, platelet removal rate and red blood cell recovery rate were measured and calculated in the same manner as in Example 1. The results are shown in Table 10.

From Table 10, in Example 5, by using the filter in which the filter media A, B, C1 and C2 are combined, the time required for treating the concentrated red blood cells (filtration time) is very short, and the leukocyte removal rate and platelet removal are It is understood that both the rate and the red blood cell removal rate are good.

(Example 6) As Example 6, filter media A, B, C1, and C2 having the compositions shown in Table 11 were placed in the same container as that of Example 1 from the blood inlet port toward the blood outlet port C2, C1, B, and A. Was used in this order. Polyester non-woven fabric is used for the filter media, A and B,
A polypropylene non-woven fabric was used for the filter media C1 and C2.

CPD-added human concentrated red blood cells (type A blood pooled, stored at 4 ° C for 4 days, white blood cells 12300 / mm ³ , hematocrit (Ht) 71%, platelets 23 × 10 ⁴ / mm ³ Was poured into the filter of Example 6 at a drop of 150 cm. After the blood flow was completed, the red blood cells in the filter were washed with 50 ml of physiological saline. The filtration time, leukocyte removal rate, platelet removal rate and red blood cell recovery rate were measured and calculated in the same manner as in Example 1. The results are shown in Table 12.

From Table 12, in Example 6, by using the filter in which the filter media A, B, C1, and C2 are combined, the time required for treating the concentrated red blood cells (filtration time) is very short, and the leukocyte removal rate and platelet removal are It is understood that both the rate and the red blood cell removal rate are good.

(Example 7) As Example 7, filter media A, B1, B2, C1, and C2 having the compositions shown in Table 13 were placed in the same container as that of Example 1 from the blood inlet port toward the blood outlet port C2, C1, and B2. , B1, and A were laminated in this order. A non-woven fabric of polyester was used as the filter medium.

CPD-added human concentrated red blood cells (type A blood pooled, stored at 4 ° C for 18 days, white blood cells 10900 / mm ³ , hematocrit (Ht) 69%, platelets 15 × 10 ⁴ / mm ³ Was poured into the filter of Example 7 at a drop of 150 cm. After the blood flow was completed, the red blood cells in the filter were washed with 50 ml of physiological saline. The filtration time, leukocyte removal rate, platelet removal rate and red blood cell recovery rate were measured and calculated in the same manner as in Example 1. The results are shown in Table 14.

From Table 14, in Example 7, by using the filter in which the filter media A, B1, B2, C1 and C2 are combined, the time required for treating the concentrated red blood cells (filtration time) is very short,
It can be seen that the white blood cell removal rate, platelet recovery rate, and red blood cell removal rate are all good.

(Example 8) As Example 8, filter media A1, A2, B, and C having the compositions shown in Table 15 were placed in the same container as in Example 1 from the blood inlet to the blood outlet, C, B, A2, and A1. Was used in this order. A non-woven fabric of polyester was used as the filter medium.

CPD-added human concentrated red blood cells (type A blood pooled, stored at 4 ° C for 1 day, white blood cells 13200 / mm ³ , hematocrit (Ht) 71%, platelets 24 × 10 ⁴ / mm ³ Was poured into the filter of Example 8 at a drop of 150 cm. After the blood flow was completed, the red blood cells in the filter were washed with 50 ml of physiological saline. The filtration time, leukocyte removal rate, platelet removal rate and red blood cell recovery rate were measured and calculated in the same manner as in Example 1. The results are shown in Table 16.

From Table 16, in Example 8, by using the filter in which the filter media A1, A2, B, and C were combined, the time required for treating the concentrated red blood cells (filtration time) was very short, and the leukocyte removal rate and platelet removal were It can be seen that both the rate and the red blood cell recovery rate are good.

{Example 9} The same filter materials A, B, and C as in Example 1 were laminated in the order of C, B, C, and A from the blood inlet to the blood outlet. That is, filter media B and A of the filter of Example 1
A filter was prepared by adding filter material C between the two, and this was used.

CPD-added human concentrated red blood cells (type A blood pooled, stored at 4 ° C for 14 days, leukocytes 12000 / mm ³ , hematocrit (Ht) 73%, platelets 16 × 10 ⁴ / mm ³ Was dropped on the filter of Example 9 with a drop of 150 cm. After the blood flow was completed, the red blood cells in the filter were washed with 50 ml of physiological saline. The filtration time, leukocyte removal rate, platelet removal rate and red blood cell recovery rate were measured and calculated in the same manner as in Example 1. The results are shown in Table 17.

From Table 17, between the filter media A and B of the filter of Example 1,
It can be seen that even if the filter medium C having a larger XY than these is added, there is substantially no effect.

(Example 10) The same filter media A, B, and C as in Example 1 were laminated in the order of C, B, A, and B from the blood inlet to the blood outlet. That is, a filter was prepared by adding the filter medium B to the most outlet side of the filter medium of Example 1 and used.

CPD-added human concentrated red blood cells (type A blood pooled, stored at 4 ° C for 14 days, white blood cells 12200 / mm ³ , hematocrit (Ht) 72%, platelets 17 × 10 ⁴ / mm ³ Was applied to the filter of Example 10 with a drop of 150 cm. After the blood flow was completed, the red blood cells in the filter were washed with 50 ml of physiological saline. The filtration time, leukocyte removal rate, platelet removal rate and red blood cell recovery rate were measured and calculated in the same manner as in Example 1. The results are shown in Table 18.

From Table 18, on the blood outlet side of the filter of Example 1,
It can be seen that even if the filter medium B having a larger XY than the filter medium A is added, there is substantially no effect.

(Example 11) As Example 11, the same filter as in Example 1 and
Drip chamber with polyester mesh (filtration area
9 cm ² ) was used. A drip chamber was arranged on the upstream side of blood, and the filter of Example 1 was installed on the downstream side.
The average fiber diameter of the polyester mesh in the drip chamber was 100 μm, the average interfiber spacing was 140 μm, and XY was 14000.

CPD-added human concentrated red blood cells (type A blood pooled, stored at 4 ° C for 21 days, white blood cells 10400 / mm ³ , hematocrit (Ht) 71%, platelets 12 × 10 ⁴ / mm ³ Was applied to the filter of Example 11 with a drop of 150 cm. After the blood flow was completed, the red blood cells in the filter were washed with 50 ml of physiological saline. The filtration time, leukocyte removal rate, platelet removal rate and red blood cell recovery rate were measured and calculated in the same manner as in Example 1. The results are shown in Table 19.

From Table 19, in Example 11, by using the filter in which the filter media A, B, C (D, E) are combined, the time required for treating the concentrated red blood cells (filtration time) is very short, and the leukocyte removal rate is It can be seen that the platelet removal rate and red blood cell recovery rate are good.

(Effects of the Invention) By using the leukocyte-trapping filter of the present invention to selectively remove leukocytes and microaggregates from blood, particularly concentrated erythrocytes, the state of preservation of concentrated erythrocytes and the state of generation of microaggregates may be used. Instead, it became possible to process concentrated red blood cells in a short time. Further, since the white blood cell capture filter of the present invention has a small pressure loss due to the filter, it is possible to perform blood filtration using only gravity, a device such as a pump is not required, and a large number of samples can be collected by one person. It can be processed. The present invention eliminates the inconvenience that it takes a long time to process concentrated red blood cells by the gravity filtration method, some of them end early, and some of them take time at a stroke.

[Brief description of drawings]

FIG. 1 is a schematic sectional view showing an example of the constitution of the leukocyte capture filter of the present invention. 1 ... Container 2 ... Blood inlet 3 ... Blood outlet 4 ... Filter medium A 5 ... Filter medium B 6 ... Filter medium C 7, 8 ... Ends of filter medium A and B

Claims (2)

(57) [Claims] 1. A filter material comprising a fibrous substance, at least 1.
A white blood cell separation filter filled in at least one container having one blood inlet and at least one blood outlet, wherein the average fiber diameter of the fibrous substance is X (μ
m), the average inter-fiber spacing defined by the following equation (1) is Y (μ
m) has at least three types of filter media A, B and C, filter media A is 7XY, filter media B is 50XY> 7, and media C is
A leukocyte-capturing filter for concentrated red blood cells, which satisfies XY> 50, and further has filter media arranged in the order of C, B, and A from the blood inlet to the blood outlet. Where Y is the average interfiber spacing (μm), X is the average fiber diameter (μm), ρ is the density of the fibrous material (g / cm ³ ), D is the bulk density of the filter medium (g / cm ³ ), and π is It is the pi. 2. At least four kinds of filter media A, B, D and E are provided, the filter media A being 7XY, the filter media B being 50XY> 7, and the filter media D being
1100XY> 50, filter medium E satisfies XY> 1100,
Further, the filter medium is E from the blood inlet to the blood outlet,
The leukocyte-trapping filter for concentrated red blood cells according to claim 1, which is arranged in the order of D, B, and A.