WO1996014890A1 - Membrane de filtration de plasma a filament creux et module de filtration de plasma - Google Patents

Membrane de filtration de plasma a filament creux et module de filtration de plasma Download PDF

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Publication number
WO1996014890A1
WO1996014890A1 PCT/JP1995/002265 JP9502265W WO9614890A1 WO 1996014890 A1 WO1996014890 A1 WO 1996014890A1 JP 9502265 W JP9502265 W JP 9502265W WO 9614890 A1 WO9614890 A1 WO 9614890A1
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WO
WIPO (PCT)
Prior art keywords
plasma
hollow fiber
filtration membrane
membrane
filtration
Prior art date
Application number
PCT/JP1995/002265
Other languages
English (en)
Japanese (ja)
Inventor
Michio Kanno
Kiyonobu Okamura
Osamu Kaneko
Hiroshi Kamogawa
Original Assignee
Mitsubishi Rayon Co., Ltd.
Otsuka Pharmaceutical Factory, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mitsubishi Rayon Co., Ltd., Otsuka Pharmaceutical Factory, Inc. filed Critical Mitsubishi Rayon Co., Ltd.
Priority to AU38157/95A priority Critical patent/AU3815795A/en
Publication of WO1996014890A1 publication Critical patent/WO1996014890A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/26—Polyalkenes
    • B01D71/261—Polyethylene
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/26—Polyalkenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3496—Plasmapheresis; Leucopheresis; Lymphopheresis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/02—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/08—Hollow fibre membranes

Definitions

  • the present invention relates to a hollow fiber type plasma filtration membrane for plasma filtration and a plasma filtration module. More specifically, a filtration membrane and a plasma filtration module suitable for separating a gel containing multiple pathological substances formed by cooling plasma obtained by separating blood from blood. About.
  • Plasmapheresis is a treatment method in which blood is separated into blood cell components and plasma components by extracorporeal circulation, harmful substances in the plasma components are removed, and then mixed with the blood cell components again and returned to the body. .
  • centrifugal separation There are two methods for separating blood cell components and plasma components: centrifugal separation and membrane filtration.
  • a membrane that is free from platelet contamination, has a small and inexpensive device, and is easy to separate.
  • the filtration method is common.
  • Plasmapheresis first discards all plasma containing separated pathogens and replaces it with normal plasma.
  • Substitution method (PE) is the basis.
  • PE requires a large amount of fresh frozen plasma of 2-3 liters per treatment, making it difficult to secure the volume of normal human plasma, and in addition to viral infection due to transfusion. It is dangerous and has fundamental problems as a versatile treatment. Due to the high cost of treatment, the indication is now limited to some cases such as drug addiction and fulminant hepatitis.
  • Examples of the material of the film used for PE include polyethylene, polypropylene, polystyrene, cellulose acetate, cellulose acetate, and the like.
  • DFPP double filtration plasma exchange method
  • Examples of the material of the film used for DFPP include ethylene vinyl alcohol, cellulose acetate, and the like.
  • CF is cooled by cooling plasma separated online to a temperature above its freezing point and below 35 ° C, thereby reducing the amount of plasma, fibrinogen, and fibronectin.
  • This is a treatment method in which a gel-like macromolecule (cryogel, CG) with the nucleus as the core is formed, and the CG is removed using a PE or DFPP membrane instead.
  • CG gel-like macromolecule
  • the power of CG has not yet been elucidated
  • the advantage of this method is that the composition of the cryogel can be changed by changing the plasma cooling conditions and the filter washing conditions.
  • CG itself also functions as a kind of adsorbent, and small and medium molecular weight substances such as amyloid protein, which cannot be removed only by the molecular sieve effect, can be adsorbed by affinity for cryogel.
  • small and medium molecular weight substances such as amyloid protein, which cannot be removed only by the molecular sieve effect, can be adsorbed by affinity for cryogel.
  • CF can reduce the loss of albumin more than DFPP because the effect of separating CG and albumin can be improved by changing the method such as cooling conditions and washing conditions. It has the feature of being able to
  • plasma separators and plasma component separators used in PE have been diverted as they are and have been used for more than 10 years until the current research treatment.
  • the filtration module that has been conventionally diverted to CF has a problem in that the separation efficiency of CG containing multiple pathogens and albumin of useful proteins is insufficient.
  • the present inventors have started to develop a film material most suitable for CF, and have focused on a biorefinable polyolefin film.
  • cellulosic for example, “Plasma Flow AP — 06 MJ made by Asahi Medical Co., Ltd.” was often used for CF, and the force (literature: 0 m 0 kawa S, eta 1, Trans ASAI 0, As described in 33, 112, 198 7), polyethylene membranes have better biocompatibility in plasma polishes than cellulose acetate membranes. For example, it is shown as specific data such as little change in complement titer (CH50), leukocytes, and platelets.
  • CH50 complement titer
  • the plasma component separation membrane made of polyethylene for example, those disclosed in JP-A-58-75555 and JP-A-63-68176 are known. Have been. The latter is for AIDS virus removal. Nevertheless, none of them are considered to be used for CF at all, so that, of course, the study of suitable specifications for improving the separation effect of CG and albumin has been completely done. Absent.
  • One object of the present invention is to provide a membrane material suitable for CF, which is excellent in biocompatibility and has a high separation efficiency between CG and albumin.
  • Yet another object of the present invention is to provide a filtration module suitable for CF.
  • the present inventors have focused on the capture rate (rejection rate) of a latex standard particle having a membrane separation coefficient of 0.1 zm, and have studied a plurality of polyrefin hollow fibers having different rejection rates.
  • rejection rate rejection rate
  • the present invention provides a method of separating blood into blood cells and plasma.
  • a hollow fiber type filtration membrane for cooling the separated separated plasma to a temperature not lower than its freezing point and not higher than 35 ° C, and removing a gel containing a medium-molecular-weight pathogenic substance from the cooled separated plasma;
  • the filtration membrane is composed of a polyolefin, the hollow fiber has an inner diameter of 50 / m or more and 300 ⁇ m or less, and is composed of 0.1 l ⁇ m of polystyrene latex particles.
  • Another object of the present invention is to provide a hollow fiber type plasma filtration membrane having a rejection of 90% or more and 99% or less.
  • the present invention comprises a cylindrical case and a plurality of the above-mentioned hollow fiber type plasma filtration membranes arranged in the case, wherein the case has at least a plasma inlet, a waste liquid outlet and a filtrate.
  • a plasma filtration module provided with an outlet, wherein the hollow fiber type plasma filtration membrane is fixed in the case by at least one partition and the inside of the case is The filtration membrane and the partition partition the space occupying the inner surface of the filtration membrane and the space occupying the outer surface of the filtration membrane.
  • the plasma inlet and the drainage outlet are connected to one of the spaces, Also, the filtrate outlet is connected to the other of the above-mentioned spaces, thereby providing a plasma filtration module.
  • the plasma filtration module may include a washing liquid inlet in addition to the plasma inlet, the waste liquid outlet, and the filtrate outlet.
  • the hollow fiber membrane is composed of polyolefin, it is excellent in biocompatibility and has a rejection of 0.1 m of polystyrene latex particles of 90%. Since it is not more than 99% or less, the removal rate of albumin can be significantly reduced as compared with the hollow fiber membrane conventionally used as a substitute.
  • FIG. 1 is an enlarged cross-sectional view showing one embodiment of the hollow fiber type plasma filtration membrane of the present invention.
  • FIG. 2 is a schematic explanatory view showing one embodiment of the plasma filtration module of the present invention.
  • FIG. 3 is a schematic explanatory view showing another embodiment of the plasma filtration module of the present invention.
  • FIG. 4 is a schematic explanatory view showing still another embodiment of the plasma filtration module of the present invention.
  • FIG. 5 is a schematic explanatory view showing still another embodiment of the plasma filtration module of the present invention.
  • Figure 6 is the circuit diagram used in the performance experiment.
  • Fig. 1 is an enlarged cross-sectional view of a hollow fiber type plasma filtration membrane according to the present invention.
  • the filtration membrane 1 is composed of a polyolefin.
  • Polyolefins include ethylene, propylene, 1-butene, 1-pentene, 1-hexene, and 4—methylol 1-pentene Etc. or a copolymer of two or more of these homopolymers.
  • Polyethylene homopolymer or polyethylene from the viewpoint of moldability. rather good to adopt a copolymer of other O-les-off fin, main Norre door Lee down de click Waals forces, '1 to 1 5 at a density Kaka' 0.
  • the inner diameter d of the filtration membrane 1 is appropriately selected and determined from a range of 50 m or more and 300 m or less.
  • a particularly preferable range of the inner diameter d is from 150 to 300111.
  • the thickness t is not particularly limited. Usually, the thickness t is appropriately selected and determined from a range of 20 to 100 m.
  • the method for producing the filtration membrane 1 includes, for example, the melt spinning and drawing aperture method described in JP-B-63-35726, JP-B-63-2004, and the like. Is available. That 1-1 5 of main Le Bokui Nde' click scan values and 0. 9 5 5 (: ⁇ less inherently branched having 3 or more density po Re ethylene les down (linear Po Re ethylene les down) In a temperature range of about 20 ° C or more from the melting point of the polymer and not exceeding 80 ° C, a spinning draft 100 to 1 using a hollow fiber manufacturing nozzle.
  • melt-spinning is performed in the range of 0.000 and the obtained highly oriented crystalline undrawn hollow fiber is subjected to an annealing treatment at a polymer melting point or lower as required, a temperature of 40 ° C or lower is obtained.
  • Cold stretching is then performed in a temperature range of 80 to 125 ° C in one stage or multiple stages, and the total stretching amount of the cold stretching and the hot stretching is 100 to By performing heat setting in the temperature range of 100 to 125 ° C as needed, a hollow fiber type filtration membrane can be manufactured. You.
  • the rejection of 0.11 m polystyrene latex particles is 90% or more and 99% or less.
  • 90% or more and 95% or less are selected and used, which can significantly reduce the albumin removal rate.
  • the hollow fiber filtration membrane of the present invention is preferably subjected to a treatment for increasing the affinity with water so as to favor the filtration of plasma.
  • a method of the treatment for example, a method of successively treating with alcohol and polyethylene glycol described in Japanese Patent Publication No. 3-64544 is common.
  • the measurement of rejection of latex standard particles can be performed by the following method.
  • a large number of hollow fiber membranes are used by filling them in a container so that the total membrane area is 50 cm 2 .
  • the hollow fiber membrane was mixed with ethanol and 0.1% (wZV) of a surfactant (polyethylene glycol (P)). (Water) to increase the affinity with water.
  • a surfactant polyethylene glycol (P)
  • a suspension containing 0.1% (WZV) monodisperse polystyrene latex particles (particle diameter: 0.1 m) is subjected to a pressure of 0.1 T kg Z cm by the hollow fiber membrane. After filtration, the concentration of the latex particle suspension before and after filtration was measured using a Hitachi spectrophotometer (U-340) to measure the absorbance at a wavelength of 320 nm. And calculate the rejection rate.
  • WZV 0.1%
  • FIGS. 2 to 5 schematically show various types of plasma filtration modules according to the present invention.
  • the plasma filtration module shown in Figure 2 is preferably cylindrical Is provided with a cylindrical case 2 and a plurality of hollow fiber type plasma filtration membranes 1 according to the present invention installed in the case 2 ( FIG. The book is shown. Normally, about 200 to 100 books are installed per case.
  • the above case 2 is provided with a washing liquid inlet 6 as required in addition to the plasma inlet 3, the drainage outlet 4 and the filtrate outlet 5.
  • the filtration membranes 1 are fixed to the inside of the case 2 via partition walls 7, 7 at two locations at both ends.
  • the inside of the case 2 is composed of a filter membrane 1... and partition walls 7, 7, a space occupying the inner surface side of the filter membrane 1, ie, an inner chamber 8, and a space occupying the outer surface side of the filter membrane 1, ie, an outer chamber 9. It is divided into
  • the plasma inlet 3 and the drain outlet 4 are respectively connected to the inner chamber 8, and the filtrate outlet 5 and the washing liquid inlet 6 are connected to the outer chamber 9, respectively.
  • the above-mentioned filtration membranes 1 ... are folded back in a U-turn, and accordingly, only one partition wall 7 is provided.
  • the plasma inlet 3 and the drainage outlet 4 are respectively connected to the outer chamber 9 side, and the filtrate outlet 5 is connected to the inner chamber 8 side.
  • FIG. 5 shows the reverse type of FIG. 4.
  • the plasma inlet 3 and the drainage outlet 4 are individually connected to the inner chamber 8 via both ends 1a and 1b of the filtration membrane 1.
  • the filtrate outlet 5 is connected to the outer chamber 9.
  • the resulting porous polyethylene hollow fiber membrane had an inner diameter of 22.5 ⁇ m, a thickness of 35; «m, a porosity of 72%, and 0.1 l. "m The rejection of styrene latex particles was 92%, which satisfied the constituent requirements of the hollow fiber type plasma filtration membrane of the present invention.
  • Example 2 Using the same polyethylene as in Example 1, according to the production method described in Example 1, inner diameter 270 / zm, film thickness 55 m, porosity 70% 0.1 A porous polyethylene hollow fiber membrane with a rejection of 90% for ⁇ m polystyrene latex particles was manufactured.
  • 1 1 is a blood pump
  • 1 2 is a blood line
  • 13 is a plasma separator
  • 14 is a plasma pump
  • 15 is a cooling section
  • 16 is a plasma line
  • 16 a is an on-off valve
  • 18 is the return line
  • 19 is the woma
  • 20 is the inlet pressure gauge
  • 21 is the outlet pressure gauge
  • 22 is the waste line
  • 2a is the waste line.
  • On-off valve, 23 is physiological saline
  • 24 is collecting pipe
  • 25 is branch pipe
  • 25a is on-off valve
  • 26 is branch pipe
  • 26a is on-off valve
  • 27 is cleaning liquid pump
  • Reference numeral 8 denotes an on-off valve
  • reference numeral 29 denotes a plasma pool.
  • the plasma separator 13 had a nominal pore diameter of 0.3 m, an inner diameter of 350 / m, a film thickness of 50 zm, and a membrane.
  • a 0.5 m 2 polystyrene hollow fiber membrane (“Plasma Flow OP — 05” manufactured by Asahi Medical Co., Ltd.) is used, and the CF filter module 17 is filled with hollow. Yarns having the specifications shown in Table 1 were used.
  • the plasma flow rate was 30 ml / min and the plasma throughput was 4 liters.
  • the cooling temperature of the plasma was adjusted to 10.5 ° C, and the washing and regenerating method of the filtration module 17 was, for example, the method described in W092-17202. That is, the filter module 17 clogged, and when the difference between the pressure gauges 20 and 21 reached 30 OmmHg, the on-off valve 28 was closed first, and then 22a is opened to lower the internal pressure of the filtration module 17 to atmospheric pressure, and then the on-off valves 16a and 22a are closed to collect useful proteins trapped in the filtration module.
  • the opening and closing valves 25a and 28 are opened, and physiological saline is supplied to the filtration module in a volume of 30 ml Z until the specified volume is reached, and useful proteins are collected.
  • ethyl alcohol is passed through the inside of the hollow fiber membrane at a flow rate of 100 m1Z so as to pass through the membrane and exit to the outside, and the air in the micropores of the hollow fiber membrane is removed by alcohol.
  • the treatment was carried out by flowing a polyethylenated alcohol at 100 ml for 1 minute for 5 minutes instead of alcohol.
  • Table 1 shows the results of the removal rate of albumin and G obtained using the hollow fiber membrane of each specification.
  • the removal rate is defined by the following equation. r After filtration, the plasma protein content ⁇
  • Comparative Example 1 a commercially available polypropylene plasma component separation membrane “Diacrystal II” (manufactured by Mitsubishi Rayon Co., Ltd.) was used as Comparative Example 2.
  • a hollow fiber membrane having the specifications and performance shown in Table 1 manufactured according to the manufacturing method described in Example 1 was used as a comparative example 3 as a conventional alternative filtration module, a hollow fiber membrane.
  • “Plasma Flow AP-0.6 M” manufactured by Asahi Medical Co., Ltd., nominal pore size 0.2 ⁇ m
  • the volume of physiological saline used for the recovery of useful proteins was 100 ml for polypropylene and polyethylene, and 200 ml for Senoroku-Sui-Acetate.
  • the amount of physiological saline used to backwash CG was 300 m 1 for both.
  • the CG removal rate was measured according to the method described in the literature (Abe, eta1 Trans ASAI 0, 30, 2989 to 2994, 1984) Calculated from the concentration of cryo-presipitab 1 eprotein.
  • the rejection rate of latex particles from the CG removal rate of 0.Polyethylene hollow fibers with a force of 90% or more and 99% or less The hollow fiber inner diameter of the hollow fiber membrane is 50 zm or more and 300 m or less.
  • the finalizers of Examples 1 and 2 exhibited a CG removal rate of 60% or more, although the removal rate of albumin was suppressed to a low level.
  • the filters using the conventional substitute membrane were used. Very high separation efficiency compared to filter The results showed good performance.
  • the finoleta of Comparative Example 3 was made of cellulose diacetate and had poor biocompatibility compared to polyolefin and had a latex rejection of 95%. Even at this point, the albumin removal rate was 52%, much higher than the 28% and 33% in Examples 1 and 2, and the performance was not good.
  • the separation efficiency of substance A from substance B refers to the ratio of the removal rate of substance B to the removal rate of substance A.
  • the separation efficiency of CG from albumin can be obtained by dividing the CG removal rate by the albumin removal rate.
  • the removal rate of albumin can be significantly reduced as compared with a filtration module which has been used in the past as a substitute.
  • CG can be removed in a sufficient amount, and the separation efficiency can be greatly improved, and the replenishment of albumin can be reduced.
  • the filtration membrane is composed of polyolefin, it has excellent biocompatibility.

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  • Chemical Kinetics & Catalysis (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Vascular Medicine (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • External Artificial Organs (AREA)

Abstract

Membrane de filtration de plasma à filament creux et module de filtration de plasma, destinés à être utilisés pour séparer le sang en cellules et plasma, refroidir le plasma séparé à une température comprise entre son point de solidification et 35 °C, et en extraire un gel contenant des substances pathogènes de poids moléculaire moyen à élevé. L'utilisation, comme membrane de filtration, d'une membrane constituée d'une polyoléfine formée en un filament possédant un diamètre interne compris entre 50 et 300 νm et présentant un taux d'inhibition compris entre 90 et 99 % contre le passage de particules de latex de polystyrène de 0,1 νm, permet d'obtenir un module présentant une excellente biocompatibilité et un faible taux d'élimination d'albumine.
PCT/JP1995/002265 1994-11-09 1995-11-06 Membrane de filtration de plasma a filament creux et module de filtration de plasma WO1996014890A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU38157/95A AU3815795A (en) 1994-11-09 1995-11-06 Hollow-filament plasma-filtering membrane and plasma-filtering module

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP27466194 1994-11-09
JP6/274661 1994-11-09

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WO1996014890A1 true WO1996014890A1 (fr) 1996-05-23

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004024216A1 (fr) * 2002-09-12 2004-03-25 Asahi Medical Co., Ltd. Membrane et systeme de purification du plasma

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5675164A (en) * 1979-11-22 1981-06-22 Asahi Chemical Ind Device for treating blood
JPS5731869A (en) * 1980-05-29 1982-02-20 Japan Fuaundeishiyon Fuo Aatei Method and device for removing macromolecule from physiological liquid according to filtration in on-line system
JPS5846962A (ja) * 1981-09-17 1983-03-18 東レ株式会社 血液処理用装置
JPS60142860A (ja) * 1983-12-29 1985-07-29 三菱レイヨン株式会社 ウイルスの除去方法
JPS61254203A (ja) * 1984-12-27 1986-11-12 Mitsubishi Rayon Co Ltd 微多孔質膜
JPH04272768A (ja) * 1991-02-27 1992-09-29 Terumo Corp 白血球除去フィルター
JPH0679149A (ja) * 1992-05-13 1994-03-22 Pall Corp インテグリティー試験の可能な湿潤−乾燥可逆性限外濾過膜およびその試験法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5675164A (en) * 1979-11-22 1981-06-22 Asahi Chemical Ind Device for treating blood
JPS5731869A (en) * 1980-05-29 1982-02-20 Japan Fuaundeishiyon Fuo Aatei Method and device for removing macromolecule from physiological liquid according to filtration in on-line system
JPS5846962A (ja) * 1981-09-17 1983-03-18 東レ株式会社 血液処理用装置
JPS60142860A (ja) * 1983-12-29 1985-07-29 三菱レイヨン株式会社 ウイルスの除去方法
JPS61254203A (ja) * 1984-12-27 1986-11-12 Mitsubishi Rayon Co Ltd 微多孔質膜
JPH04272768A (ja) * 1991-02-27 1992-09-29 Terumo Corp 白血球除去フィルター
JPH0679149A (ja) * 1992-05-13 1994-03-22 Pall Corp インテグリティー試験の可能な湿潤−乾燥可逆性限外濾過膜およびその試験法

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004024216A1 (fr) * 2002-09-12 2004-03-25 Asahi Medical Co., Ltd. Membrane et systeme de purification du plasma
US7563376B2 (en) 2002-09-12 2009-07-21 Asahi Kasei Kuraray Medical Co., Ltd. Plasma purification membrane and plasma purification system

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