JPH119687A - Leucocyte removing filter material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a leucocyte removing filter material which has high leucocyte removability per unit volume, is good in the flow of a leucocyte-contg. liquid and incurs less damage on blood cells. SOLUTION: This leucocyte removing filter material is a filter material consisting of a porous element and a fibrous structure of >=0.03 μm and <1.0 μm in the fiber diameter held at a porous element. The void volume of the filter material is >=50% and <95%. The fibrous structural material of the leucocyte removing filter material is cellulose microfibrils within 1.0% in the degree of expansion of the fiber length by water. The filter material is capable of removing the leucocytes which are the cause for the side effect of transfusion with high efficiency from the leucocyte-contg. liquid and the high recovery rate of the useful blood components is obtainable. Further, the damage that the useful blood components receives is less and, therefore, the material is extremely useful as the filter material of the leucocyte removing filter material to be used at the time of the transfusion.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a leukocyte removal filter material for removing leukocytes from a leukocyte-containing liquid.

[0002]

2. Description of the Related Art In recent years, in the field of blood transfusion, in addition to so-called whole blood transfusion, a recipient of a whole blood product is required in addition to so-called whole blood transfusion, in which an anticoagulant is added to blood collected from a donor. What is called component blood transfusion is generally performed in which a blood component is separated and the blood component is transfused. Component transfusions include erythrocyte transfusions, platelet transfusions, plasma transfusions, etc., depending on the type of blood component required by the recipient.The blood component preparations used for these transfusions include erythrocyte preparations, platelet preparations, and plasma preparations. and so on. In recent years, so-called leukocyte-removal transfusion, in which a blood product is transfused after removing leukocytes mixed in the blood product, has become widespread.
This includes relatively minor side effects such as headache, nausea, chills, and non-hemolytic fever reactions associated with blood transfusion, alloantigen sensitization that has a serious effect on recipients, viral infection, and GVHD after blood transfusion.
It has been clarified that such serious side effects are caused mainly by leukocytes mixed in blood products used for blood transfusion. Headache, nausea, chills,
It is said that in order to prevent relatively minor side effects such as fever, leukocytes in blood products should be removed until the residual ratio becomes 10 ^-1 to 10 ^-2 or less. It is also said that leukocytes should be removed until the residual ratio becomes 10 ^-4 to 10 ^-6 or less in order to prevent alloantigen sensitization and virus infection, which are serious side effects.

[0003] Methods for removing leukocytes from blood products include:
It is roughly divided into a centrifugal separation method that separates and removes white blood cells using the difference in specific gravity of blood components using a centrifugal separator, and a filter material made of a porous material such as a fiber material or a porous material having continuous pores. There are two types of filter methods for removing leukocytes. The filter method has been widely used at present because of its advantages such as excellent leukocyte removing ability, simple operation, and low cost. Furthermore, among the filter methods, a method of removing leukocytes by adhesion or adsorption using a nonwoven fabric as a filter material,
It is most widely used at present because of its excellent leukocyte removal ability. The mechanism of the leukocyte removal by the filter device using the fiber material or the porous body is mainly based on the fact that the leukocytes in contact with the surface of the filter material adhere or adhere to the surface of the filter material. For example, EP-A
0155003 discloses a technique using a nonwoven fabric as a filter material. In addition, fiber diameter 0.01μm
Hereinafter, a lump composed of a large number of small fiber pieces having a length of about 1 to 50 μm and a spinnable short fiber having a fineness of about 0.05 to 0.75 d and an average length of 3 to 15 μm are dispersed in a dispersion medium. The leukocyte-removing filter material produced by dispersing in a dispersion medium and removing the dispersion medium from the obtained dispersion is WO93 / 018.
80.

[0004]

The current leukocyte removal filter has a leukocyte removal ability of a residual leukocyte count of 1 × 10 ⁵ or less. Under such circumstances, two major demands for leukocyte depletion filters have been raised in the market. The first requirement is to improve the recovery ratio of useful components and to eliminate the need to recover the useful components remaining in the filter and circuit due to the presence of physiological saline and air, thereby improving handling. It is. In particular, blood, which is a raw material of blood products, is often valuable blood provided by blood donation in good faith, and blood that remains in the leukocyte removal filter and cannot be collected is discarded together with the filter and is wasted. Because it becomes
Improving the recovery of useful components over current leukocyte removal filters is extremely significant. However, with the leukocyte removal filter using the conventional technique, it is difficult to significantly improve the recovery of useful components. A second need is to achieve higher leukocyte rejection rates than current leukocyte depletion filters and completely prevent the serious side effects caused by leukocytes infused into patients. However, it is difficult for a leukocyte removal filter using a conventional technique to achieve a leukocyte removal rate high enough to completely prevent such side effects. An object of the present invention is to provide a leukocyte-removing filter material having a leukocyte-removing ability per unit volume which is extremely higher than that of a conventional filter material, and in which the flow of a leukocyte-containing liquid is good, and furthermore, red blood cells, platelets, and the like. An object of the present invention is to provide a leukocyte-removing filter material having good blood compatibility and having little adverse effect on blood cells.

[0005]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, a porous element and an ultrafine fiber structure held by the porous element have been obtained. In a leukocyte-removing filter material having a specific porosity, the use of cellulose microfibrils whose fiber length swelling degree with water is within 1.0% for a superfine fiber structure has surprisingly high leukocyte-removing ability. The present inventors have found that a leukocyte-removing filter material having a good flow of a leukocyte-containing liquid, good blood compatibility, and a stable filter structure can be obtained, thereby completing the present invention. That is, the present invention relates to a filter material comprising a porous element and a fiber structure having a fiber diameter of 0.03 μm or more and less than 1.0 μm held by the porous element, wherein the porosity of the filter material is 50%. In the leukocyte-removing filter material of not less than 95%, the fiber structure has a fiber length expansion degree of 1.0 by water.
% Of cellulosic microfibrils.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The term "fiber diameter" as used in the present invention means the diameter of each fiber when a nonwoven fabric is observed with a scanning electron microscope. Fibers having a fiber diameter of less than 0.03 μm are not suitable for the purpose of the present invention because the fibers have a low fiber strength and are liable to be cut by white blood cells or other blood cell components that collide when processing a leukocyte-containing liquid. . The fiber diameter is 1.0μ
Fibers of m or more do not contribute to capturing some lymphocytes having particularly low adhesion among leukocytes. In order to efficiently capture low-viscosity lymphocytes and the like having relatively small diameters among leukocytes by contacting the filter material at multiple points, the fiber diameter of the cellulose microfibril is 0.03 μm.
It is more preferable that the number of m is larger than m and less than 0.8 μm. Cellulose microfibrils are divided by physical stimulation, and a submicron order obtained by fibrillating splittable cellulose having the property of fibrillating by stirring with a mixer, jetting with a high-pressure liquid flow, high-pressure homogenizer treatment, etc. It is a cellulose fiber with a small diameter. The cellulose microfibril of the present invention needs to have a fiber length swelling degree of 1.0% or less when changed from a dry state to a wet state with water. The fiber length of the same cellulose microfibril in a dry state and a water-wet state is measured under a microscope, and the value defined by the following formula (1) is defined as the degree of swelling of the fiber length by water. Fiber length can be measured directly under a microscope, but cellulose microfibrils are often curved, so take a micrograph and then measure the length on the photograph or use an image analyzer. It is preferable to perform the measurement using It is also preferable that the number of measurements be a statistically significant number. If the degree of swelling of the fiber length of cellulose microfibril due to water is more than 1%, the probability of damaging the surface of blood cells such as red blood cells and platelets is high because fibrils inhale water at the moment of contact with blood in a dry state, which is preferable. Absent. The degree of expansion of the fiber length by water is 1%
If it is larger, the form of fibrils changes at the moment of contact with blood, and the structure of the leukocyte removal filter material may change. The preferred range of the degree of swelling of the fiber length by water is 0.5% or less, more preferably 0.1% or less, and most preferably 0.05% or less.

In the leukocyte removal filter material of the present invention, the porosity must be 50% or more and less than 95%. If the porosity of the filter material is less than 50%, the flow of the leukocyte-containing liquid becomes poor, and is not suitable for the purpose of the present invention. If the porosity is 95% or more, the mechanical strength of the filter material is weakened, and the filter material is easily crushed when treating a leukocyte-containing liquid, and thus is not suitable for the purpose of the present invention. The porosity is measured by measuring the dry weight (W ₁ ) of the filter material cut into a predetermined area, and further measuring the thickness to calculate the volume (V). This filter material is immersed in pure water, degassed, and the weight (W ₂ ) of the hydrated filter material is measured. From these values, the porosity is determined by the following calculation formula. Note that ρ in the following calculation formula
Is the density of pure water. Porosity (%) = (W ₂ −W ₁ ) × ρ × 100 / V As the porous element referred to in the present invention, a fiber aggregate, a porous membrane, a sponge-like continuous porous body, or the like can be used. As the porous element, a fiber assembly is particularly preferable.
Preferred forms of the fiber aggregate include a nonwoven fabric, a woven fabric, and a knitted fabric, and a nonwoven fabric is particularly preferred. The material of the porous element is to form a nonwoven fabric, a woven fabric, a knitted fabric, a porous film, a sponge-like continuous porous body, such as polyurethane, polyester, polyolefin, polyamide, polystyrene, polyacrylonitrile, cellulose, and cellulose acetate. Any material can be used as long as the material can be used. The average pore diameter of the leukocyte removal filter material is preferably 1.0 μm or more and less than 100 μm. Here, the average pore diameter refers to a value obtained by measurement by a bubble point method. For example, using a Coulter R porometer manufactured by Coulter Electronics Co., Ltd., about 50
The average pore size (mean flow pore size: MFP) can be measured using mg sample. If the average pore diameter is less than 1.0 μm, the leukocyte-containing liquid becomes difficult to flow, which is not preferable. If it is 100 μm or more, it is often difficult to maintain the fibrous structure, which is not preferable. A more preferable range of the average pore diameter is 1.5 μm or more and less than 50 μm, and further preferably 2.0 μm or more and less than 25 μm.
In the fibrous structure of the present invention, it is preferable that cellulose microfibrils having an extremely small average fiber diameter form a network structure. It is preferable that the reticulated cellulose microfibrils are present so as to cover the pores of the porous element as the substrate and fixed to the substrate.

The physical structure of the preferred filter material of the present invention will be described below. In the filter material of the present invention, a plurality of cellulose microfibrils having a fiber diameter of 0.03 μm or more and less than 1.0 μm form a network structure to form a fiber structure, and the fiber structure is used for a porous element. Is held. However, the cellulose microfibrils constituting the network structure are not bundled, and are so-called single fibers in which each fiber is in an opened state. Are physically entangled to form a network structure. As a mesh structure,
Since the cellulose microfibrils have a curved structure, the formed network tends to have a curved structure. It is preferable that the network-like cellulose microfibrils are uniformly held by the porous element in a cross section perpendicular to the flow of the leukocyte-containing liquid, because leukocytes can be efficiently captured. The fact that cellulose microfibrils are uniformly held in the porous element in a cross section perpendicular to the flow of the leukocyte-containing liquid means that the filter material is randomly sampled in a cross section perpendicular to the flow of the leukocyte-containing liquid. Means that the introduction amount (density) of cellulose microfibrils in each part of the filter material is substantially equal, and this introduction amount is actually the amount of cellulose microfibrils present in a certain amount of filter material in each part of the sampled filter material. It can be obtained by measuring the variation of the amount. In addition, in the cross section perpendicular to the flow of the leukocyte-containing liquid, the amount of cellulose microfibrils introduced into each part of the randomly sampled filter material is almost equal, and the distribution of the mesh size in each part is It is particularly preferable that substantially the same and substantially the same network structure is formed. In this specification, such a state is expressed as “a uniform mesh structure is formed”. More specifically, a uniform network structure is formed when the network structure in each part of the filter material sampled at random is a distribution of a network having a size similar to that observed by an electron microscope. And a similar mesh pattern, and are considered to be substantially the same. When a uniform network structure is not formed, the distribution of the mesh size in each part differs greatly when observing the network structure in each part of the filter material sampled at random, and the form is also clear. State that can be determined to be different. The leukocyte removal filter material of the present invention is characterized in that a cellulose microfibril having a fiber diameter of 0.03 μm or more and less than 1.0 μm is held in a porous element. It is suitable for taking a preferred structure of the material, and the above-mentioned network structure is also formed in a preferred form.

[0009] Cellulose microfibrils having a fiber length swelling degree of 1.0% or less due to water forming a network structure are hard to be cut even when wet with blood despite being thin, and have appropriate softness. As a result, red blood cells can pass through without excessive deformation, have low resistance to liquid permeation, and cause little damage to red blood cells even when blood comes into direct contact with a dry leukocyte removal filter material. Further, it is considered that cellulose microfibrils have strong affinity for leukocytes because of their thinness, and can be firmly captured. In addition, since the material of cellulose microfibrils having a fiber length expansion of 1.0% or less due to water used in the present invention is cellulose, the affinity for blood cells such as erythrocytes and platelets is originally low, and these cells are weak. Since it is a material that is difficult to stimulate, blood compatibility is also satisfactory.

Further, the cellulose microfibrils used in the present invention have a fiber length swelling degree of not more than 1.0% due to water. Shape is maintained properly and is less likely to change. Further, in the leukocyte-removing filter material of the present invention, the holding amount of the cellulose microfibrils to the filter material is 0.01 wt.
% Or more and less than 30 wt%. If the retained amount is less than 0.01% by weight, a sufficient amount of fibers to capture leukocytes in the leukocyte-containing liquid cannot be obtained, which is not suitable for the purpose of the present invention. When the holding amount is 30 wt% or more,
Since the amount of fibers introduced into the porous element becomes too large, the pores of the porous element are closed and the leukocyte-containing liquid does not flow, which is not suitable for the purpose of the present invention. The holding amount of the cellulose microfibrils to the filter material is 0.0
More preferably, it is at least 3 wt% and less than 10 wt%. The measurement of the retained amount can be determined from the change in weight before and after retaining the cellulose microfibrils in the porous element. When the retained amount of cellulose microfibrils is as small as less than about 3 wt% per unit weight of the filter material, only the cellulose microfibrils are dissolved in order to obtain the retained amount of cellulose microfibrils more accurately than the weight measurement. And a method of quantifying the extracted components. The quantification method is specifically described as follows. The leukocyte-removing filter material of the present invention is immersed and shaken in a solution in which cellulase is dissolved, and the cellulose of the cellulose microfibrils is decomposed into glucose to extract glucose. The extracted glucose is quantified using a commercially available glucose quantification reagent, and the amount of cellulose microfibrils retained in the porous element is calculated from the obtained amount of glucose.
In order to achieve a high leukocyte removal ability, it is preferable that cellulose microfibrils are held on the entire porous element. However, if it is difficult to hold the cellulose microfibrils deep inside the porous element due to limitations due to the manufacturing method, the cellulose microfibrils may be held on one surface of the porous element, In such a case, cellulose microfibrils may be retained on both surfaces of the porous element as a means for easily increasing the retention amount of cellulose microfibrils and improving the leukocyte removal ability of the filter material. In any case, it is preferable to keep the cellulose microfibrils substantially uniformly on the porous element in order to achieve high leukocyte removal ability.

The preferred thickness of the leukocyte removal filter material of the present invention is 0.1 mm or more in the flow direction of the leukocyte-containing liquid.
Preferably it is less than 0 mm. If the thickness is less than 0.1 mm, the frequency of collision between the leukocytes in the leukocyte-containing liquid and the filter material decreases, and it is difficult to achieve high leukocyte removal ability, which is not preferable. When the thickness is 30 mm or more, the passage resistance of the leukocyte-containing liquid is increased, which is not preferable because the treatment time is prolonged and hemolysis is caused by destruction of the erythrocyte membrane. More preferably, the thickness of the filter material in the flow direction is 0.1 mm or more and less than 15 mm. When the leukocyte-removing filter material of the present invention is treated with a binder such as a water-insoluble polymer solution as a post-process, generally, cellulose microfibrils constituting a fibrous structure are bundled into bundles, It is preferable not to treat with such a binder because it may break the preferred network structure, such as forming a film between a plurality of cellulose microfibrils. On the other hand, when the physical entanglement between the cellulose microfibril and the porous element is insufficient, the leukocyte removal filter material of the present invention is subjected to post-processing with a binder such as a relatively dilute water-insoluble polymer solution. The treatment is preferable because cellulose microfibrils can be effectively fixed to the porous element and the fibers can be prevented from falling off. The surface of the leukocyte removal filter material of the present invention may be modified to a surface to which platelets or erythrocytes are not easily adhered, thereby improving the recovery of platelets and erythrocytes, and removing only leukocytes. Methods for modifying the filter material surface include surface graft polymerization,
Examples include coating of a polymer material or discharge treatment. A polymer material having a nonionic hydrophilic group is preferably used as a polymer material used for modifying the surface of a filter material by surface graft polymerization or coating with a polymer material. Examples of the nonionic hydrophilic group include a hydroxyl group, an amide group, and a polyethylene oxide chain. Examples of monomers that can be used in the synthesis of a polymer material having a nonionic hydrophilic group include, for example, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, and vinyl alcohol (a polymer obtained by polymerizing vinyl acetate. Prepared by hydrolysis), methacrylamide, N-vinylpyrrolidone, and the like. Among the above monomers, 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate are preferred from the viewpoints of availability, ease of handling during polymerization, and processing performance of a leukocyte-containing liquid. The polymer material used for the surface graft polymerization or the coating of the polymer material is a polymer material having a polymerizable monomer having a nonionic hydrophilic group and / or a basic nitrogen-containing functional group as a monomer unit.
It is preferred that the copolymer contains 1 to 20 mol%.
Examples of the basic nitrogen-containing functional group include a primary amino group, a secondary amino group, a tertiary amino group, and a quaternary ammonium group.
And a nitrogen-containing aromatic ring group such as a pyridyl group and an imidazole group. Examples of the polymerizable monomer having a basic nitrogen-containing functional group include dimethylaminoethyl methacrylate,
Derivatives of methacrylic acid such as diethylaminoethyl methacrylate, dimethylaminopropyl methacrylate, 3-dimethylamino-2-hydroxypropyl methacrylate, allylamine, p-vinylpyridine, vinyl derivatives of nitrogen-containing aromatic compounds such as 4-vinylimidazole,
And quaternary ammonium salts obtained by reacting the vinyl compound with an alkyl halide or the like. Among the above polymerizable monomers, dimethylaminoethyl methacrylate and diethylaminoethyl methacrylate are preferred from the viewpoint of easy availability, easy handling during polymerization, and processing performance of a leukocyte-containing liquid. When the monomer unit content of the polymerizable monomer having a basic nitrogen-containing functional group in the obtained copolymer is less than 0.1%, the effect of suppressing platelet adhesion to the filter material surface is not so much seen, which is not preferable. . Further, when the monomer unit content of the polymerizable monomer having a basic nitrogen-containing functional group in the copolymer is 20% or more, not only leukocytes but also useful components such as platelets and erythrocytes easily adhere to the filter material surface. Not preferred. More preferably, the content of the polymerizable monomer having a basic nitrogen-containing functional group in the copolymer is from 0.2 to 5% as a monomer unit.

Hereinafter, a method for producing a leukocyte removal filter material will be exemplified. Fiber diameter is 0.03μm or more and 1.0μ
Cellulose microfibrils of less than m, for example, physically stirring a splittable cellulose fiber typified by lyocell, superpolynosic, etc. using a mixer, spraying a high-pressure liquid stream, treating with a high-pressure homogenizer, etc. Can be manufactured. A method for obtaining cellulose microfibrils having the above specific fiber diameter by subjecting splittable cellulose fibers to an acid treatment or an alkali treatment as necessary, and then physically stirring in a liquid using a mixer or the like to fibrillate. Is particularly preferable because the fiber diameter becomes extremely small, and a fiber having a curved shape can be easily obtained, and the fiber easily forms a network structure. This method of obtaining fibers having a fiber diameter of 0.03 μm or more and less than 1.0 μm by fibrillating splittable cellulose fibers will be described in more detail below. First, a commercially available splittable cellulose fiber having a fiber diameter of about 12 μm is cut into a predetermined length, immersed in an aqueous solution of about 3 wt% sulfuric acid, and subjected to an acid treatment at 70 ° C. for 30 minutes while stirring gently. After the acid-treated splittable cellulose fibers are washed with water and vigorously stirred in water at 10,000 rpm for 30 minutes to 90 minutes, the splittable cellulose fibers are fibrillated and reduced in diameter. Cellulose microfibrils can be obtained. The thus obtained cellulose microfibril having a fiber diameter of 0.03 μm or more and less than 1.0 μm is dispersed in a dispersion medium so as to have a concentration of about 0.01 g / L to about 1 g / L. Obtain a fibril dispersion. As a dispersion medium, in addition to pure water, a surfactant is used in an amount of about 0.1%.
An aqueous solution containing 1% to 5%, or an aqueous solution in which the viscosity is increased by adding about 0.1% to 5% of polyacrylamide in order to further improve the dispersibility of cellulose microfibrils is used. Next, a porous element is placed on the bottom of the funnel-like container, and the above-mentioned cellulose microfibril dispersion is poured into the container, and once collected and drained at a stretch, the porous element is dried to dry the porous element of the present invention. Filter material can be obtained. In the present invention, such a production method is referred to as papermaking. At this time, it is preferable that the cellulose microfibrils be short, because they can be held deep inside the porous element. The filter material produced by the production method of the above, the further about 3 kg / cm ² 200
Applying a high-pressure liquid flow treatment of kg / cm ² is preferable because cellulose microfibrils can be held more uniformly and deep inside the porous element in the thickness direction. Further, when the material of the porous element is a fiber,
The fibers and cellulose microfibrils may be mixed in advance to make a sheet at once.

Next, a leukocyte removal filter device using the leukocyte removal filter material of the present invention will be exemplified. The leukocyte removal filter device is a device in which a filter including the filter material of the present invention is appropriately filled in at least a container having an inlet and an outlet. One or more filter materials may be stacked in the flow direction of the leukocyte-containing liquid and filled in the container. On the other hand, when a solution containing a polymer material is poured into the filter material for the purpose of surface modification of the filter material and a coating process is performed, the lowermost filter material in the apparatus of the present invention is stuck to the inner wall of the container. This may cause an uneven flow of the leukocyte-containing liquid. In such a case, by inserting a relatively coarse filter material into the lowermost layer, it is possible to prevent the uneven flow of the leukocyte-containing liquid caused by the filter material sticking to the inner wall of the container. The leukocyte removal filter device may further include another filter material upstream and / or downstream of the filter material. Generally, the leukocyte-containing liquid often contains microaggregates. A prefilter can also be used to remove leukocytes from a leukocyte-containing liquid containing a large amount of such microaggregates. As the prefilter, an aggregate of fibers having an average fiber diameter of 8 μm to 50 μm or a continuous porous body having pores having an average pore diameter of 20 μm to 200 μm is preferably used. The cross-sectional area perpendicular to the flow direction of the leukocyte-containing liquid of the filter material of the leukocyte removal filter device is preferably 3 cm ² or more and less than 100 cm ² . If the cross-sectional area is less than 3 cm ² , the flow of the leukocyte-containing liquid becomes extremely poor, which is not preferable. If the cross-sectional area is 100 cm ² or more, the thickness of the filter must be reduced, and a high leukocyte removal ability cannot be achieved, and the filter device is undesirably increased in size.

Hereinafter, a method for removing leukocytes from a leukocyte-containing liquid using the leukocyte removal filter device including the leukocyte removal filter material of the present invention will be described. The leukocyte removal method comprises treating a leukocyte-containing liquid with a leukocyte removal filter device and collecting the filtered liquid. More specifically, using a device including 1) an inlet, 2) a filter including the filter material of the present invention, and 3) an outlet, a leukocyte-containing liquid is injected through the inlet, and filtered through the filter through the outlet. This is a method for removing leukocytes from a leukocyte-containing liquid, which comprises recovering the liquid that has cleaved. Examples of the leukocyte-containing liquid to be filtered by the leukocyte removal filter device include a whole blood product, a concentrated red blood cell product, a concentrated platelet product, and a body fluid.
When the leukocyte-containing liquid is a whole blood product or a concentrated erythrocyte product, it is preferable to treat the leukocyte-containing liquid with a leukocyte removal filter device having a unit volume of 3 mL or more and less than 20 mL. Here, one unit is about 300 mL
Refers to whole blood products or concentrated red blood cell products in an amount of from .about.550 mL. If the device capacity per unit is less than 3 mL, a high leukocyte removal rate may not be achieved, which is not preferable. If the unit capacity per unit is 20 mL or more, the loss of useful components in the unrecoverable leukocyte-containing liquid remaining inside the device, in other words, the amount of useful components, is not preferable. By filtering the whole blood product or the concentrated erythrocyte product with a leukocyte removal filter device, leukocytes in the collected liquid can be removed to a residual white blood cell count of less than 1 × 10 ³ cells / unit. When the leukocyte-containing liquid is a concentrated platelet preparation, it is preferable to treat the leukocyte-containing liquid with a leukocyte removal filter device having a device capacity per unit of 1 mL or more and less than 10 mL. Here, 5 units means
Refers to a concentrated platelet product in an amount of about 170 mL to 200 mL. If the device capacity per 5 units is less than 1 mL, a high leukocyte removal rate cannot be easily achieved, which is not preferable. If the device capacity per 5 units is 10 mL or more, unrecoverable useful components remaining inside the device increase, which is not preferable. By filtering the platelet concentrate preparation in the leukocyte removal filter apparatus of the present invention, the white blood cells in recovered liquid can be removed to less than the residual leukocyte number 1 × 10 ³ cells / 5 units. When using a leukocyte removal filter device to perform transfusion at the hospital bedside and simultaneously remove leukocytes, it is preferable to filter the leukocyte-containing liquid at a rate of 1 g / min or more and less than 20 g / min. On the other hand, when leukocytes are removed from a blood product for transfusion at a blood center using a leukocyte removal filter device, 20
It is preferable to filter the leukocyte-containing liquid at a rate of at least g / min and less than 100 g / min. The leukocyte removal filter device
In addition to removing leukocytes which cause various side effects after blood transfusion from blood products for transfusion, they can also be used for the purpose of removing leukocytes in extracorporeal circulation therapy for autoimmune diseases. Extracorporeal circulation therapy for autoimmune diseases consists of removing leukocytes from body fluids by continuously filtering the patient's body fluid, which is a leukocyte-containing fluid, with a leukocyte removal filter device and returning the recovered fluid to the body. . As described above, the leukocyte-removing filter material of the present invention has an extremely high affinity for leukocytes, and thus can efficiently process a leukocyte-containing liquid without lowering the processing speed. In addition, it has excellent blood compatibility and has little damage to red blood cells and platelets.

[0015]

The present invention will be described in more detail with reference to the following examples, but the scope of the present invention is not limited to these examples.

Example 1 Cellulose microfibrils were prepared by the following method. Monofilament fiber diameter about 12
μm lyocell yarn (Tencel R, manufactured by Coatles) is cut to a length of about 3 mm, 1 g of the cut lyocell yarn is dispersed in 1 L of pure water, and the lyocell system is sufficiently formed while applying mechanical vibration to the liquid. Split and microfibrillated. When the degree of expansion of the fiber length of the obtained cellulose microfibrils due to water was measured on a micrograph, it was 0.03.
%Met. The fiber diameter is from 0.03 μm to 0.8 μm
Was distributed between Polyester staple fibers having an average fiber diameter of 1.2 μm were dispersed in pure water so as to have a ratio of 0.9 g to 0.1 g of the cellulose microfibrils to prepare a mixed solution of two kinds of fibers. Next, the mixed solution was formed on a mesh and vacuum-dried at 40 ° C. for 16 hours to obtain a leukocyte removal filter material. The thickness of the obtained leukocyte-removing filter material was 0.2 mm, the average pore diameter measured by a bubble point method (Coulter R porometer, manufactured by Coulter Electronics Co., Ltd.) was 6.0 μm,
The porosity was 81%, and the retained amount of cellulose microfibrils with respect to the entire filter material was 10% by weight. When the filter material was observed with an electron microscope, it was confirmed that the cellulose microfibrils had a network structure. The porosity is measured by measuring the dry weight (W ₁ ) of a filter material cut into a circle having a diameter of 25 mm and measuring the thickness using a peacock to calculate the volume (V). This filter material is immersed in pure water, degassed while irradiating ultrasonic waves for about 30 seconds, and then the weight (W ₂ ) of the hydrated filter material is measured. From these values, the porosity was determined by the following calculation formula. In addition,
In the following formula, ρ is the density of pure water, and 1.0 g / cm ³ was substituted in this experiment. Porosity (%) = (W ₂ −W ₁ ) × ρ × 100 / V The measurement of the amount of retained ultrafine fibers was performed by the following method.
That is, 0.1 mol / L acetate buffer (pH 4.8) 1
Cellulase (made by Wako Pure Chemical Industries, Ltd.) 50 in 00 mL
Three filter materials cut into a circle having a diameter of 25 mm are immersed in 5 mL of a solution in which mg is dissolved. Shake gently at 50 ° C. for 24 hours to decompose and extract the ultrafine fibers into glucose. Glucose decomposed and extracted is quantified using glucose CII-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.), which is a glucose quantification reagent, and the amount of ultrafine fibers introduced into the porous element is calculated from the amount of glucose. did.

The filter material 1 produced as described above
A stack of zero sheets is used to form an effective filtration section of 9.0 cm ^2.
(3.0 cm × 3.0 cm) to prepare a leukocyte removal filter device. The total volume of the filter material was 1.8 cm ³ . 56 mL of CPD solution (composition: sodium citrate 26.3 g / L, 400 mL of blood)
3.27 g / L citric acid, 23.20 g / glucose
L, sodium dihydrogen phosphate dihydrate 2.51 g / L)
After centrifugation of 456 mL of whole blood prepared by adding MAP, platelet-rich plasma was removed, and 95 mL of MAP solution (composition: sodium citrate 1.50 g / L, citric acid 0.20 g /
L, glucose 7.21 g / L, sodium dihydrogen phosphate dihydrate 0.94 g / L, sodium chloride 4.97 g
/ L, adenine 0.14 g / L, mannitol 14.5
7 g / L) to prepare concentrated red blood cells (RC-MA
P) was prepared. Rich red blood cells (R
C-MAP: hematocrit value 59%, leukocyte count 6,4
(00 cells / μL) and 50 g were filtered with the above leukocyte removal filter device. The temperature of the concentrated red blood cells immediately before the start of the filtration was 10 ° C. Filtration of the concentrated red blood cells by the filter device was performed at a head of 1.0 m, filtration was performed until there was no concentrated red blood cells in the blood bag, and the filtered blood was collected (hereinafter, the collected concentrated red blood cells are referred to as a collected liquid). ). The average processing speed when filtering the concentrated red blood cells was 9.8 g / min. Rich red blood cells before filtration (hereinafter referred to as pre-filtration liquid)
In addition, the volume of the recovered liquid and the number of leukocytes were measured, and the leukocyte residual ratio was determined. Leukocyte residual ratio = (the number of leukocytes in the recovered liquid) / (the number of leukocytes in the pre-filtration liquid) The volumes of the pre-filtration liquid and the collected liquid were each divided by the specific gravity of the blood product (1.075). Value. The leukocyte concentration of the pre-filtration solution was measured by injecting the pre-filtration solution diluted 10-fold with the Turk solution into a Bürker-Turk type hemocytometer and counting the number of leukocytes using an optical microscope. The measurement of the leukocyte concentration of the recovered solution was performed by the following method. The recovered solution is diluted to 5 times with a leuco plate solution (manufactured by SOBIODA). After thoroughly mixing the diluent, the mixture was allowed to stand at room temperature for 6 to 10 minutes. This was centrifuged at 2,750 × g for 6 minutes, and the supernatant was removed to adjust the liquid amount to 1.02 g. After the sample solution was mixed well, the mixture was poured into a nadget type hemocytometer, and the number of leukocytes was counted using an optical microscope to measure the leukocyte concentration. As a result, the leukocyte residual rate was 10 ^-3.45 . In addition, when the first 2 mL of blood filtered by the leukocyte removal filter device was collected and the amount of free hemoglobin in plasma was examined, no difference was observed between before and after filtration.

[0017]

Industrial Applicability The leukocyte-removing filter material of the present invention can remove leukocytes, which cause side effects of blood transfusion, from a leukocyte-containing liquid with high efficiency, and can obtain a high recovery rate of useful blood components. It is very useful as a filter material for a leukocyte removal filter used at the time of blood transfusion because it receives less damage.

Claims (1)

[Claims] 1. A filter material comprising a porous element and a fiber structure having a fiber diameter of 0.03 μm or more and less than 1.0 μm held by the porous element, wherein the porosity of the filter material is 50%. The leukocyte-removing filter material having a leukocyte-removing filter material of not less than 95% and the fiber structure is a cellulose microfibril having a fiber length expansion of 1.0% or less due to water.