JPH0347131A - Filter material for capturing leukocyte and production thereof - Google Patents

Abstract

PURPOSE:To obtain the subject filter material exhibiting stable leukocyte capturing ability and capable of sterilizing in highpressure steam without fear of intermixing of foreign material comprising polymer porous body having fixed ranges of pore diameter, specific surface area, porosity, bubble point and thickness. CONSTITUTION:The aimed filter material is composed of polymer porous body having three-dimensional netty continuous texture, 1-60mum, especially 5-20mum averaged pore diameter, 0.5-10m<2>/g, especially 1.5-3.0m<2>/g specific surface area, 30-95%, especially 60-95% porosity, 0.08-0.40kg/cm<2>, preferably 0.13-0.27kg/cm<2> bubble point and 0.3-9.0mm, especially 0.5-3.0mm thickness. As said polymer, polyurethane, polyvinylidene fluoride, polysulfone or polyester, etc., is used. Raw material composition containing polymer material, good solvent of said polymer and pore-forming agent soluble in non-solvent miscible with said solvent is extruded and shaped, then dipped into a bath containing said non-solvent as principal ingredient to be made to gel and simultaneously said pore forming agent is removed by elusion to afford the aimed filter.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a filter material for capturing white blood cells and a method for manufacturing the same. Specifically, the present invention relates to a filter material for capturing white blood cells that exhibits a stable ability to capture leukocytes and is free from the risk of contamination with foreign matter, and a method for producing the same. The present invention further relates to a filter material for capturing white blood cells that can be sterilized by high-pressure steam, and a method for manufacturing the same.

(Prior Art) The form of blood transfusion has long since changed from the traditional whole blood transfusion to component transfusion, in which only the components needed by the patient are transfused.
In this blood component transfusion, the issue is how to increase the purity of the fractionated blood components. Conventionally, blood obtained through blood donation is processed into concentrated red blood cells (C) by centrifugation.
RC), platelet-rich plasma (PC) and platelet-poor plasma (PPP). The concentrated red blood cell solution separated in this way is widely used as a component preparation of red blood cells for component transfusion to patients who require red blood cells.
The idea that concentrated red blood cells contain a large number of white blood cells and is so-called whole component blood is becoming established, and patients who only need red blood cells are transfused with a large amount of white blood cells when they are transfused with concentrated red blood cells. Being there is considered a problem. As described above, white blood cells contained in red blood cell fractions such as concentrated red blood cells must be removed as much as possible in order to prevent side effects after blood transfusion, and many efforts have been made to this end. Methods for increasing the purity of red blood cell preparations include gravity centrifugation that utilizes the difference in specific gravity of blood cells, methods that utilize capture materials that utilize the adhesion or adhesion of blood cells, and leukocyte separation methods that use red blood cell agglutination agents. method is used.

Among these Li;
It is required that the captured leukocytes do not detach during washing and collection operations using physiological saline, etc., which aim to efficiently capture leukocytes and improve the red blood cell yield. In many cases, the capture material used is natural cellulose, polyester, polyamide, polyacrylonitrile, glass fiber, etc., which are packed with very small diameter fibers in the column or processed into non-woven fabric. .

However, when packing the fibers themselves into a column in the above method, it is difficult to uniformly pack the fibers, which takes time and effort, and there is a great risk of channeling during operation depending on the way the fibers are packed. If the packing density of the fibers is increased to ensure sufficient capture of the It was something.

Furthermore, when the fibers are processed into non-woven fabrics or the like, although the above-mentioned problems are less likely to occur, the problem remains that clogging due to trapped blood cells is likely to occur.

Various proposals have been made to use porous bodies as capture materials in place of such fibers.

For example, in Japanese Patent Publication No. 61-39060, the average pore diameter is 25.
The use of porous bodies with continuous pores of ~60 μm has been proposed. However, this technique attempts to capture monocytes and granulocytes by taking advantage of the fact that they have higher adhesiveness than other blood cells; This was not sufficient to satisfy the desire to capture and remove all leukocytes.

In addition, the average pore diameter of JP-Koku No. 63-26089 is 5 to 2.
The use of porous bodies with continuous pores of 0 μm is described. It is stated that this technique attempts to capture white blood cells through their adhesive properties and filtration through pores. However, what is specified in this technology is only the size of the pores of the porous body, and in fact, various types of porous materials that have such a pore size and have a different porosity and bubble point than those of the present invention are As a result of the leukocyte separation experiments conducted by the present inventors using porous materials, effective leukocyte separation was often not achieved, especially when the porous material was considerably thick, specifically, at least 10 mm thick. It has become clear that, unless it is a specific material, a somewhat satisfactory leukocyte trapping property can hardly be obtained. If the thickness of the porous body used as a trapping material is as large as 1Q mm or more, there is a problem that not only is clogging caused by trapped blood cells likely to occur, but also the priming volume increases and the filtration time becomes longer. At the same time, disadvantages such as time lag also occurred.

Furthermore, the use of a polyvinyl formal porous body having a continuous three-dimensional network structure having continuous open pores with an average pore diameter of 5 to 60 μm has been proposed as a filter system for capturing white blood cells (Japanese Patent Application Laid-open No. 75014/1983). This porous material made of polyvinyl formal is different from the porous material mentioned above in which only the pore size is controlled, and by taking advantage of its complex pore structure, relatively efficient white blood cell removal can be expected even in thin walls. It was something. By the way, in the future, there will be demand for an in-line type filter that incorporates a filter into a blood bag system as such a white blood cell trapping filter, and in general, blood bags made of flexible resin such as vinyl chloride resin The blood bag system that stores drugs inside is sterilized using autoclave sterilization, so in order to use such an in-line leukocyte capture filter, it must also be resistant to autoclave sterilization. It's something that comes. However, the filter material made of the polyvinyl formal porous material cannot withstand high-pressure steam sterilization, so it has been difficult to apply it to such uses.

As described above, the current situation is that a capturing material that exhibits sufficient and stable performance as a filter for capturing white blood cells has not yet been obtained. The purpose of this research is to provide materials and methods for producing the same. Another object of the present invention is to provide a filter material for capturing leukocytes that has a high and stable capturing ability for leukocytes and can separate leukocytes more efficiently from blood, and a method for producing the same. A further object of the present invention is to provide a leukocyte-trapping filter material and a method for manufacturing the same, which can safely perform leukocyte removal operations without fear of foreign matter flowing out during operation. Another object of the present invention is to provide a leukocyte-trapping filter material that can be autoclaved and a method for producing the same.

(Means for Solving the Problems) The above-mentioned materials are made of at least one kind of polymeric material, and have an average pore diameter of 1 to 60 μm, a specific surface area of 0.5 to 1
0m2/g, porosity 30-95%, bubble point 0.08-0.40kg/cm2, wall thickness 0.3-9.
This is achieved by using a filter material for capturing white blood cells that can be sterilized by high-pressure steam and is made of a three-dimensional mesh continuous porous material with a diameter of 0 mm.

The present invention also provides an average pore diameter of 2 to 50 μm, more preferably 5 to 20 μm, a specific surface area of 1 to 5 m2/g, more preferably 1.5 to 3.0 m2/g, and a porosity of 50 to 95.
%, more preferably 60-95%, bubble point is 0
．． 13~0.27kg/cm2, wall thickness 0.5~5,
It shows a filter material for capturing white blood cells whose diameter is more preferably 0.5 to 3.0 mm. The present invention also provides that the polymeric material comprises the group consisting of polyurethane, polyvinylidene fluoride, polysulfone, polyethersulfone, polyester, poly(meth)acrylate, butadiene-acrylonitrile copolymer, polyamide, polyether polyamide block copolymer and ethylene-vinyl alcohol copolymer. This shows a leukocyte-trapping filter material selected from the following. The present invention further provides a filter material for capturing leukocytes in which the polymeric material is polyurethane.

The above-mentioned examples include one or more polymeric materials, a good solvent for the polymeric material, and one or more types of pore formation that dissolve or swell in a non-solvent that is compatible with the good solvent. A raw material composition containing a pore-forming agent is extruded and shaped using an extruder, and then introduced into a bath containing a non-solvent for the polymer material as a main component and immersed in the bath to gelatinize the material and at the same time remove the pore-forming agent from its good solvent. A method for producing a filter material for capturing white blood cells, which comprises at least one polymeric material, a good solvent for the polymeric material, and a non-solvent that is compatible with the good solvent. By coating the surface of a substrate with a raw material composition containing one or more pore-forming agents that dissolve or swell in This can also be achieved by a method for producing a filter material for capturing leukocytes, which is characterized in that the pore-forming agent is eluted and removed into a good solvent at the same time as gelation is performed.

The present invention also provides that the polymeric material is polyurethane, polyvinylidene fluoride, polysulfone, polyethersulfone, polyester, poly(meth)acrylate, butadiene-
The present invention describes a method for producing a filter material for capturing white blood cells, which is selected from the group consisting of acrylonitrile copolymer, polyamide, polyether polyamide block copolymer, and ethylene-vinyl alcohol copolymer. The present invention further provides a method for producing a filter material for capturing white blood cells, in which the polymeric material is polyurethane. The present invention also provides a method for producing a filter material for capturing white blood cells, in which the pore-forming agent is a water-soluble compound. The present invention further provides a method for producing a filter material for capturing white blood cells, in which the pore-forming agent is a water-soluble polymer. The present invention further provides that the pore forming agent is polyvinyl alcohol, polyvinylpyrrolidone, methyl cellulose,
polyether, polysaccharide, polyacrylic acid or its salt,
This figure shows a method for manufacturing a leukocyte-trapping filter material selected from the group consisting of polyacrylamide.

(Function) Therefore, the filter material for capturing leukocytes of the present invention is made of at least one kind of polymeric material, and has an average pore diameter of 1.
~60μm1 specific surface area 0.5~10 m2/g
s Porosity is 30~95%, bubble point is 0.08~
It is characterized by being composed of a three-dimensional network continuous porous body having a weight of 0.40 kg/cm2 and a wall thickness of 0.3 to 9.0 mm.

This is a porous polymer material whose matrix has a continuous three-dimensional network structure and which satisfies the characteristics of pore diameter, specific surface area, porosity, bubble point, and wall thickness within a certain range as described above. Alternatively, when a white blood cell suspension such as a concentrated red blood cell solution is processed, the white blood cells contained in the white blood cell suspension pass through a complicated flow path consisting of continuous open pores formed between the matrix of a porous material, and are then deposited on the inner surface of the pores. It is adsorbed and collected efficiently. Furthermore, the flow path of the filter material is
It is a three-dimensional network-like continuous structure of the porous body, that is, continuous open pores formed by the matrix of the porous body. Therefore, since the flow path of the filter material is formed during molding of the porous material, the manufacturing process for manufacturing the filter material for leukocyte capture using the porous material is extremely simple, and the product performance is The variation in will be small. Further, since the matrix of the porous body is a continuous structure, it is stable, and problems such as foreign matter flowing out from the porous body or channeling of flow paths during operation do not occur. Furthermore, such a porous polymer material is
For example, since it can be formed from a relatively heat-resistant resin such as polyurethane, it can sufficiently withstand high-pressure steam sterilization.

Hereinafter, the present invention will be explained in more detail based on embodiments.

In the filter material for capturing white blood cells having the above structure according to the present invention, the average pore diameter of continuous open pores is 1
The thickness is preferably 60 μm, more preferably 2 μm to 50 μm, and most preferably 5 μm to 20 μm. In other words, if the pore size is less than 1 μ■, during the leukocyte removal operation,
Even red blood cells contained in the processed blood and white blood cell suspensions such as red blood cell concentrates are trapped, reducing the red blood cell recovery rate and causing clogging due to the overwhelming number of red blood cells being trapped. On the other hand,
This is because if the pore size exceeds 60 μm, the frequency of contact with the leukocyte suspension to be treated will decrease, which may lead to a decrease in the capture rate of leukocytes. Note that the "average pore diameter" in this specification represents a value measured by mercury intrusion method.

In addition, the leukocyte-trapping filter material of the present invention has a specific surface area of 0.5 to 10 m2/g, preferably 1 to 5 m2/g.
g, most preferably 1.5 to 3°0 m2/g. In other words, if the specific surface area is less than 0.5 m2/g, the amount of leukocyte capture is too small to be practical;
This is because if it exceeds 2/g, the pore diameter may become too small. Note that the "specific surface area" in this specification represents a value measured by mercury porosimetry.

Further, the porosity of the filter material for capturing leukocytes of the present invention is 3
It is preferably about 0 to 95%, preferably about 50 to 95%, and more preferably about 60 to 95%. That is, if the porosity is less than 30%, the processing time in the leukocyte removal operation is too slow to be practical, and if the mechanical porosity exceeds 95%, the strength as a filter material is insufficient. It's for a reason. In addition, "porosity" in this specification
represents the value measured by mercury porosimetry.

Furthermore, in the filter material for capturing leukocytes of the present invention,
Bubble point is 0.08~0.40kg/cm2,
More preferably, it is 0.13 to 0.27 kg/cm2. That is, when the bubble point is less than 0.08 kg/cm2, white blood cells leak into the collected liquid, while at 0.40 kg/cm2, white blood cells leak into the collected liquid.
This is because if it exceeds g/cm2, there is a high risk of clogging. The term "bubble point" here is a term widely used in the field of porous filter materials, and is the pressure at which air is forced through the pores of a completely wetted filter material.

In addition, the wall thickness of the filter material for leukocyte separation in the present invention is 0.3 to 9. 0mm, more preferably 0.5-5
．． It is preferably about 0ma+, most preferably about 0.5-3°OmaI. In other words, if the wall thickness of the porous body is less than 0.3 mm, a sufficient amount of leukocytes cannot be captured during the leukocyte removal process;
This is because if it exceeds I11, the processing speed will be too slow to be practical.

The polymer constituting the leukocyte-trapping filter material of the present invention is not particularly limited as long as it has heat resistance that can withstand high-pressure steam sterilization, and various polymers can be used. Specific examples include polyurethane, polyvinylidene fluoride, polysulfone, polyethersulfone, polyester, poly(meth)acrylate, butadiene-acrylonitrile copolymer, polyamide, polyether polyamide block copolymer, and ethylene-vinyl alcohol copolymer. , of course, it is not limited to these.

The leukocyte-trapping filter material of the present invention enjoys the relatively good heat resistance of such a polymeric material and can sufficiently withstand high-pressure steam sterilization conditions, so it can be incorporated into, for example, a blood bag system. It can be suitably used as an in-line type leukocyte-trapping filter material. Note that polyurethane can be mentioned as one of the particularly preferable polymer materials.

The filter material for capturing white blood cells of the present invention having the above-mentioned characteristics is manufactured, for example, as follows. That is, a raw material containing at least one polymeric material, a good solvent for the polymeric material, and one or more pore-forming agents that dissolve or swell in a non-solvent that is compatible with the good solvent. After the composition is extruded and shaped using an extruder, it is introduced into a bath containing a non-solvent for the polymeric material as a main component and immersed in it to gel it, and at the same time, the pore-forming agent is eluted and removed into the good solvent. It is manufactured by

In this manufacturing method, the polymer materials used include those mentioned above, and one type or a combination of two or more types may be used. The amount of this polymeric material blended in the raw material composition is 5 to 70% by weight, more preferably 10 to 5% by weight.
Approximately 0% by weight is appropriate. That is, if the blending amount of the polymeric material is less than 5% by weight, there is a strong possibility that the resulting porous body will not have sufficient strength, while if it exceeds 70% by weight, the viscosity of the raw material composition This is because the amount increases to an extremely high level, making it difficult to handle.

As a good solvent for the polymeric material, one is used that dissolves the polymeric material used and exhibits compatibility with the non-solvent used during gelation.

Therefore, it can be appropriately selected depending on the type of polymer material used, but for example, dimethylformamide, dimethyl sulfoxide, acetone, dioxane, methylcellosolve acetate, tetrahydrofuran, ethyl alcohol, methyl alcohol, methyl ethyl ketone, phenol, formic acid, etc. aromatic hydrocarbons or chlorinated hydrocarbons,
Typical examples include fluorinated alcohols.

The pore-forming agent used may be one that dissolves or swells in a non-solvent that is compatible with the good solvent for the polymer material, although it varies depending on the polymer material and solvent used. In particular, a water-soluble compound such as a water-soluble polymer is desired because of its ease of handling. in particular,
For example, if dimethylformamide, dimethyl sulfoxide, acetone, ethyl acetate, etc. that dissolve in water, alcohol, etc., which are generally used as non-solvents, are selected as good solvents, polyvinyl alcohol, polyvinylpyrrolidone,
Methylcellulose, polyethers, polysaccharides, polyacrylic acid or its salts, polyacrylamide, and the like can be used as pore-forming agents. The amount of these pore-forming agents added is 1 to 60% by weight, more preferably 5% by weight in the raw material composition.
Approximately 50% by weight is appropriate. That is, if the amount of the pore-forming agent added is less than 1% by weight, the resulting porous material will not form the aforementioned three-dimensional network continuous structure, that is, continuous open pores formed by the matrix of the porous material. On the other hand, if it exceeds 60% by weight, the viscosity of the raw material composition will increase extremely, making it difficult to handle.

Furthermore, in this raw material composition, if necessary, 50% by weight or less, preferably 3 to 20% by weight of the raw material composition.
It is also possible to add a pore diameter F14i agent in a blending amount of . This pore size adjusting agent is one that dissolves in the non-solvent of the polymeric material, but does not dissolve in good solvents, and is compatible with the pore-forming agent, or can be uniformly mixed even if it is insoluble. For example, alginic acid, carboxymethyl cellulose, polyacrylate, various starches, dextrin, or sodium, potassium, calcium,
Inorganic salts such as chlorides and sulfates of strontium and aluminum are used.

The raw material composition containing these components is prepared at a temperature below the boiling point of the solvent, preferably about 10 to 80°C, and sufficiently stirred and mixed until a uniform dispersion is formed.

Next, the raw material composition prepared in this way is extruded and shaped using an extruder equipped with a suitable die having a flat slit at the tip, such as a T-die, to form a non-solvent for the polymer material as the main component. By being immersed in this bath, it is gelled, and at the same time, the pore-forming agent is eluted and removed into the good solvent.

The non-solvent for the polymer material may be any non-solvent as long as it is compatible with the good solvent used, and as mentioned above, water, alcohol, or a mixture thereof is usually used. Furthermore, in addition to the above-mentioned non-solvent, a good solvent for the polymeric material can be added to the bath in which such gelation is carried out, if necessary. Further, in order to achieve good gelation, the temperature of this bath is desirably maintained at a temperature of about 0 to 70°C, more preferably about 15 to 60°C. Furthermore, if the pore-forming agent is not sufficiently eluted and removed by immersion in such a bath, a cleaning step using a non-solvent may be provided after the immersion treatment, if necessary.

Alternatively, the leukocyte-trapping filter material of the present invention having the above characteristics can be dissolved in at least one polymeric material, a good solvent for the polymeric material, and a non-solvent that is compatible with the good solvent. A raw material composition containing one or more swellable pore-forming agents is coated on the surface of a base material, and gelation is achieved by introducing and immersing the raw material composition into a bath containing a non-solvent for the polymer material as a main component. It is also produced by simultaneously eluting and removing the pore-forming agent into the good solvent.

The substrate used in this manufacturing method may be, for example, a porous substrate such as a nonwoven fabric, a woven fabric, or a knitted fabric, or a dense substrate such as a glass plate, leather, or release paper. In addition, when using a porous base material,
As long as these porous base materials do not particularly affect the leukocyte capture treatment operation, the porous body according to the present invention can be formed by gelling the raw material composition and eluting and removing the pore-forming agent. There is no need to peel the porous body from the base material afterwards, and the porous base material can function as a support for the porous body.

Further, the method of coating the raw material composition is not particularly limited, and any known method such as a doctor knife method, a roller coating method, a dipping method, a spin coating method, etc. may be used.

Note that in this second manufacturing method, the details regarding other points are substantially the same as those in the first manufacturing method, and therefore a description thereof will be omitted.

FIG. 1 is a sectional view of a leukocyte-trapping filter using an embodiment of the leukocyte-trapping filter material of the present invention. In the present embodiment, the white blood cell trapping filter 1 has a white blood cell trapping filter material 5 having the above-described structure in a housing 4 comprising a blood inlet 2 and a blood outlet 3, and a white blood cell trapping filter material 5 which is arranged in the inner space of the housing 4. It is located across the In addition, in such a filter 1 for capturing white blood cells, in order to hold the filter material 5 for capturing white blood cells in the housing 4, for example, liquid-permeable supporting materials 6a16b are provided before and after the filter material 5 for capturing white blood cells, and the supporting materials It is optional to sandwich the white blood cell trapping filter material 5 by 6a s 6b.

This white blood cell trapping filter 1 is actually used by being incorporated into a circuit as shown in FIG. 2, for example. Second
In the circuit shown in the figure, a blood bag 7 containing blood to be processed and a saline bag 8 containing physiological saline are positioned above the white blood cell trapping filter 1, and are each equipped with cleansers 9a and 9b. The fluid guiding tubes 10a and 10b are connected to the blood inlet 2 of the white blood cell trapping filter 1, while a physiological saline collection bag 1 is provided below the white blood cell trapping filter 1.
1 and a blood collection bag 12 for collecting the treated blood are positioned, and communicate with the blood outflow port 3 of the white blood cell trapping filter 1 through liquid guide tubes 10c and 10d each having a drain tube 9c and 9d, respectively. has been done.

In the leukocyte separation operation, first, the drains 9b and 9c are opened, and with the drains 9a and 9d closed, physiological saline is poured from the saline bag 8 into the white blood cell trapping filter 1 to prime the inside of the leukocyte trapping filter 1.

Note that the physiological saline used for priming is collected into a physiological saline collection bag 11. After priming, open the cleaners 9a and 9d, and then clean the cleaners 9b and 9d.
9c is closed to allow blood to flow from the blood bag 7 to the white blood cell trapping filter 1. When the blood passes through the white blood cell trapping filter material 5 having the above-described configuration in the white blood cell trapping filter 1, the white blood cell components are adsorbed and captured by the white blood cell trapping filter material 5, and the white blood cells are separated. The blood from which leukocyte components have been removed in this way is collected into a communicating blood collection bag 12. blood bag 7
After draining more blood, cleanse the filter 9 again to collect the blood remaining in the leukocyte trapping filter 1.
Open b and pour physiological saline into the white blood cell trapping filter 1 again to push out the blood remaining in the white blood cell trapping filter 1 and collect it in the blood collection bag 12. 9d is closed, the drain 9c is opened, and the physiological saline used for blood collection is collected into the physiological saline collection bag 11, thereby completing the leukocyte separation operation.

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

Examples 1-5 and Comparative Examples 1-2 Polyurethane (trade name Parabrene P395RNAT.

dimethylformamide (D
MF) at 50° C. to a concentration of 20 w/v%, and after cooling to room temperature, methylcellulose as a pore-forming agent was added at a predetermined ratio shown in Table 1. Then, a stock solution was prepared by thoroughly stirring at 30°C.

Next, the stock solution prepared as described above was loaded into an extruder equipped with a T-die and extruded from a die slit into a water bath at 30°C at a temperature of 50°C to gel the stock solution. Thereafter, this gelled product was washed with water at 60°C to elute and remove the pore-forming agent, thereby obtaining a porous body.

The obtained porous body was replaced with alcohol and then dried,
Furthermore, it was subjected to high-pressure steam sterilization at 121° C. for 20 minutes and subjected to the following evaluation experiment. The results are shown in Tables 1 and 2.

Examples 6-8 and Comparative Examples 3-4 Polyurethane (trade name: Paraprene P395RNAT.

dimethylformamide (D
MF) at 50° C. to a concentration of 20 w/v%, and after cooling to room temperature, polyvinyl alcohol as a pore-forming agent was added at a predetermined ratio shown in Table 1. Then, a stock solution was prepared by thoroughly stirring at 30°C.

Next, the stock solution prepared as described above was coated onto a glass substrate using a coater at room temperature, and each glass substrate was coated for 30 minutes.
The stock solution was gelled by immersing it in a water bath at ℃. Thereafter, this gelled product was washed with water at 60°C to elute and remove the pore-forming agent, thereby obtaining a porous body.

The obtained porous body was replaced with alcohol and then dried,
Furthermore, it was subjected to high-pressure steam sterilization at 121° C. for 20 minutes and subjected to the following evaluation experiment in the same manner as in Example 1. The results are shown in Tables 1 and 2.

Comparative Example 5 An evaluation test similar to that in Example 1 was conducted using a commercially available polyvinyl formal sponge as a filter material. The results are shown in Tables 1 and 2.

Comparative Example 6 An evaluation test similar to that in Example 1 was conducted using a commercially available polyurethane foam as a filter material.

The results are shown in Tables 1 and 2.

Evaluation experiment (1) Average pore diameter mercury pressure meter (Carlo Erba Macropore Unit 120
& Porosimeter 2000).

(2) Specific surface area mercury pressure total (Carlo Erba Macropore Unit) 120
& Porosimeter 2000).

(3) Porosity mercury pressure total (Carlo Erba Macrobore Unit) 120
& Porosimeter 2000).

(4) Immediately before bubble point measurement, fill one side of the porous material with water to completely moisten it, gradually increase the air pressure on the other side, and observe a steady and continuous flow of fine bubbles as the air passes through the filter. The bubble point was defined as the pressure at which the bubble was released.

(5) Thickness Measured using a micrometer.

(6) Leukocyte removal rate A porous body punched to a diameter of 4.7 cm is fixed in a housing 4 comprising a blood inlet 2 and a blood outlet 3 as shown in FIG. The blood outlet port 15 of the blood storage container 14 is connected to the blood inlet port 2 of the filter 1 prepared by using a polyvinyl chloride tube 13a, and the blood outlet port 15 of the blood storage container 14 is connected to the blood outlet port 3 of the filter 1. A polyvinyl chloride tube 13b having approximately equal length is connected, and the open end 1 of this tube 13b is connected.
A blood collection container 17 was placed below 6. Note that the liquid level 18 of the blood contained in the blood storage container 14 and the open end 1 of the tube
The distance to 6 was 70 cm. And this 7Qcm
50 mN of blood was flowed with a head of , and the number of white blood cells in the blood before and after treatment was calculated using an automatic blood cell measuring device (ELT-8, manufactured by Ortho Instruments), and then calculated using the following formula.

(Leukocyte removal rate)%=[l-(Leukocyte ti number after filtration)/(
Blood cells the day before filtration, fi) IX100 Table Example 2 Example 3 Example 4 Example 5 Comparative example 1 Comparative example 2 Example 6 Example 7 Example 8 Comparative example 3 Comparative example 4 Comparative example 5 Comparative example 6 Methyl cellulose Methyl cellulose Methyl cellulose Methyl cellulose Methyl cellulose Methyl cellulose Polyvinyl alcohol Polyvinyl alcohol Polyvinyl alcohol Polyvinyl alcohol Polyvinyl alcohol Table 2 Leukocyte removal rate Example 1 100 Example 2 100 Example 3 98 Example 4 89 Example 5 72 Comparative Example 1 Unmeasurable Comparative Example 2 40 Example 6 100 Example 7 97 Example 8 90 Comparative Example 3 Unmeasurable Comparative Example 4 44 Comparative Example 5 99 Comparative Example 6 48 Slightly Yes No No No Yes (stopped midway) No Slightly Yes No Slightly Yes (stopped midway) No No No Comparative Example 7 For a commercially available polyvinyl formal sponge similar to that in Comparative Example 5, 121 After high-pressure steam sterilization at .degree. C. for 20 minutes, an attempt was made to conduct an evaluation test in the same manner as above, but the deformation and deterioration of the sponge were so severe that the test could not be conducted.

Example 9 and Comparative Example 8 After conducting the above experiment for calculating the leukocyte removal rate on the porous bodies in Example 3 and Comparative Example 6, 50 ml of a physiological solution containing plasma was added to the porous bodies. While flowing at a flow rate of 5 mt/min and applying vibration to the porous body, an attempt was made to recover the white blood cells captured in the porous body.

As a result, in the case of the porous body in Comparative Example 6 (Comparative Example 8
) A high recovery rate of 50% of the captured leukocytes was obtained, whereas in the case of the porous material in Example 3 (Example 9)
It was only a few percent. This result suggested that the leukocyte trapping filter according to the present invention more reliably traps leukocytes due to its three-dimensional network structure and the like.

(Effects of the Invention) As described above, the present invention is made of at least one kind of polymer material, has an average pore diameter of 1 to 60 μm, a specific surface area of 0.5 to 10 m2/g, and a porosity of 30 to 60 μm. 95%, a bubble point of 0.08 to 0°40 kg/cm2, and a wall thickness of 0.3 to 9.0 mm. It is a filter material for capturing white blood cells that can be sterilized by high pressure steam. Therefore, it has a high and stable capture ability for white blood cells,
It can efficiently remove white blood cell components from white blood cell suspensions such as blood and red blood cell concentrates with a simple operation, and it also prevents clogging and channeling during operation, as well as contamination of foreign substances due to filter media falling off. (It is possible to safely perform leukocyte removal operations, and for example, it is possible to provide red blood cell fractions used in blood component transfusions with higher purity and safety. It is also possible to be autoclaved. Therefore, the filter material of the present invention can be suitably applied as an in-line type filter material.Furthermore, since the filter material of the present invention has an extremely thin wall thickness, the priming volume is small, and the white blood cell suspension is There is no clogging even when water is passed through the filter, and the filtration time is short.

Furthermore, in the present invention, the polymeric material is a group consisting of polyurethane, polyvinylidene fluoride, polysulfone, polyethersulfone, polyester, poly(meth)acrylate, butadiene-acrylonitrile copolymer, polyamide, polyether polyamide block copolymer, and ethylene-vinyl alcohol copolymer. Any one selected from the above, more preferably polyurethane, exhibits even more stable properties even after high-pressure steam sterilization, so its uses will be further expanded.

The present invention also provides a method for forming pores that dissolves or swells in a small amount of (one or more polymeric materials, a good solvent for the polymeric material, and a non-solvent that is compatible with the good solvent). A raw material composition containing a pore-forming agent is extruded and shaped using an extruder, and then introduced into a bath containing a non-solvent for the polymer material as a main component and immersed in the bath to gelatinize the material and at the same time remove the pore-forming agent from its good solvent. A method for producing a filter material for capturing white blood cells, which comprises at least one polymeric material, a good solvent for the polymeric material, and a non-solvent that is compatible with the good solvent. By coating the surface of a substrate with a raw material composition containing one or more pore-forming agents that dissolve or swell in This method for producing a leukocyte-trapping filter material is characterized in that the pore-forming agent is eluted and removed into a good solvent at the same time as gelation, so it is easy to produce a leukocyte-trapping filter material that has the excellent properties described above. It can be made to

Furthermore, in the method for producing a filter material for capturing white blood cells of the present invention, the polymeric material may be polyurethane, polyvinylidene fluoride, polysulfone, polyethersulfone, polyester, poly(meth)acrylate, butadiene-acrylonitrile copolymer, polyamide, polyether polyamide. Any selected from the group consisting of block copolymers and ethylene-vinyl alcohol copolymers, more preferably polyurethane, and the pore-forming agent is a water-soluble compound, more preferably a water-soluble polymer, even more preferably polyvinyl alcohol. , polyvinylpyrrolidone, methylcellulose, polyether, polysaccharide, polyacrylic acid or its salt, and polyacrylamide, the properties of the obtained filter material for leukocyte capture are even more excellent. Become something.

[Brief explanation of drawings]

FIG. 1 is a sectional view showing the structure of a leukocyte-trapping filter using an embodiment of the leukocyte-trapping filter material of the present invention, and FIG. 2 is a cross-sectional view showing the structure of a leukocyte-trapping filter using an embodiment of the leukocyte-separating filter material of the present invention. FIG. 3 is a circuit diagram showing a blood processing circuit incorporating a filter for capturing leukocytes, and FIG. 3 is a drawing showing the configuration of an apparatus used for measuring leukocyte removal rate. DESCRIPTION OF SYMBOLS 1... Filter for white blood cell capture, 2... Blood inflow port, 3... Blood outflow port, 4... Housing, 5...
Filter material for capturing white blood cells, 6a, 6b...Supporting material, 7...Blood bag, 8
...Physiological saline bag, 9a, 9b, 9c, 9d -...Kremme, 10a, 1
0b, 10c, 10d--liquid guide tube, 11...
Physiological saline collection bag, 12...Blood collection bag. 13a, 13b...Tube, 14...Blood storage container, 15...Blood outlet, 16...Open end, 17...Blood collection container, 18...Blood liquid level.

Claims (10)

[Claims] (1) Made of at least one kind of polymeric material, average pore diameter of 1 to 60 μm, specific surface area of 0.5 to 10 m^2
/g) Porosity is 30-95%, bubble point is 0.0
8~0.40kg/cm^2, wall thickness 0.3~9.0m
A high-pressure steam sterilizable filter material for capturing white blood cells, which is made of a three-dimensional mesh continuous porous material having a diameter of m. (2) The polymer material is selected from the group consisting of polyurethane, polyvinylidene fluoride, polysulfone, polyether sulfone, polyester, poly(meth)acrylate, butadiene-acrylonitrile copolymer, polyamide, polyether polyamide block copolymer, and ethylene-vinyl alcohol copolymer. The filter material for capturing white blood cells according to claim 1, which is any one of the above. (3) The filter material for capturing white blood cells according to claim 1, wherein the polymeric material is polyurethane. (4) Contains at least one polymeric material, a good solvent for the polymeric material, and one or more pore-forming agents that dissolve or swell in a non-solvent that is compatible with the good solvent. After extruding and shaping the raw material composition using an extruder,
A method for producing a filter material for capturing white blood cells, which comprises introducing the polymer material into a bath containing a non-solvent as a main component and immersing it in the bath to gel it, and at the same time eluting and removing the pore-forming agent into the good solvent. . (5) Contains at least one polymeric material, a good solvent for the polymeric material, and one or more pore-forming agents that dissolve or swell in a non-solvent that is compatible with the good solvent. The raw material composition is coated on the surface of a base material and introduced into a bath containing a non-solvent for the polymeric material as a main component and immersed to gel it and at the same time to elute and remove the pore-forming agent into the good solvent. A method for producing a filter material for capturing white blood cells, characterized by: (6) The polymer material is selected from the group consisting of polyurethane, polyvinylidene fluoride, polysulfone, polyether sulfone, polyester, poly(meth)acrylate, butadiene-acrylonitrile copolymer, polyamide, polyether polyamide block copolymer, and ethylene-vinyl alcohol copolymer. The method for producing a filter material for capturing leukocytes according to claim 4 or 5, which is any one of the above. (7) The method for producing a filter material for capturing white blood cells according to claim 4 or 5, wherein the polymeric material is polyurethane. (8) The method for producing a filter material for capturing white blood cells according to any one of claims 4 to 7, wherein the pore-forming agent is a water-soluble compound. (9) The method for producing a filter material for capturing white blood cells according to any one of claims 4 to 7, wherein the pore-forming agent is a water-soluble polymer. (10) Claim 4, wherein the pore-forming agent is one selected from the group consisting of polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, polyether, polysaccharide, polyacrylic acid or a salt thereof, and polyacrylamide.
10. The method for producing a filter material for capturing white blood cells according to any one of 1 to 9.