Separation membrane for blood processing and blood processing apparatus having the membrane installed therein

Abstract

The present invention provides a separation membrane for blood processing, comprising a polysulfone polymer, a hydrophilic polymer and a polymer having a hydroxy group in a side chain and having a solubility of 0.5 g or less in water (100 g) at 20? C., in which the content of the polymer falls within a specific range, and a blood processing apparatus having the membrane installed therein.

Claims

1. A hollow-fiber separation membrane for blood processing comprising a polysulfone polymer, a hydrophilic polymer and a polymer having a hydroxy group in a side chain and having a solubility of 0.5 g or less in 100 g of water at 20? C., wherein the content of the polymer in the hollow-fiber separation membrane is 0.11 to 0.6 mass %; the average concentration of the polymer in a functional separation surface of the hollow-fiber separation membrane is 20 mass % or more, and a maximum value and a minimum value of the polymer concentration in the functional separation surface fall within the range of (the average concentration of the polymer in the functional separation surface)?15%; the average concentration of the polymer in the functional separation surface relative to the content of the polymer in the hollow-fiber separation membrane is 100 times or more; and the polymer having a hydroxy group in a side chain is a polymer obtained by polymerizing only an acrylate monomer and/or methacrylate monomer having a hydroxy group in a side chain or polymerizing so as to partly contain such a monomer.

2. The hollow-fiber separation membrane for blood processing according to claim 1, wherein the hollow-fiber separation membrane is sterilized by radiation.

3. The hollow-fiber separation membrane for blood processing according to claim 1, wherein the hydrophilic polymer is polyvinylpyrrolidone.

4. The hollow-fiber separation membrane for blood processing according to claim 1, wherein the polysulfone polymer is at least one selected from the group consisting of polysulfone, polyethersulfone, polyphenylenesulfone, polyarylethersulfone and a copolymer of these.

5. The hollow-fiber separation membrane for blood processing according to claim 1, wherein the polymer having a hydroxy group in a side chain is a polymer obtained by polymerizing only an acrylate monomer and/or methacrylate monomer having a hydroxy group in a side chain.

6. The hollow-fiber separation membrane for blood processing according to claim 1, wherein the polymer having a hydroxy group in a side chain has a weight average molecular weight of 200,000 or more.

7. The hollow-fiber separation membrane for blood processing according to claim 1, wherein the inner diameter of the hollow-fiber membrane is 180 to 220 ?m.

8. The hollow-fiber separation membrane for blood processing according to claim 7, wherein the thickness of the hollow-fiber separation membrane is 50 ?m or less.

9. The hollow-fiber separation membrane for blood processing according to claim 1, wherein the hollow-fiber membrane is formed by a spinning process in which a draft ratio is 0.95 or less.

10. The hollow-fiber separation membrane for blood processing according to claim 1, wherein the average concentration of the polymer in the functional separation surface of the separation membrane is from 20 mass % to 49 mass %.

11. The hollow-fiber separation membrane for blood processing according to claim 1, wherein the inner diameter of the hollow-fiber membrane is 170 to 250 ?m.

12. The hollow-fiber separation membrane for blood processing according to claim 1, wherein the hollow-fiber membrane is formed by a spinning process in which a draft ratio is 1 or less.

13. A blood processing apparatus in which the hollow-fiber separation membrane for blood processing according to claim 1 is installed.

Description

EXAMPLES

(1) The present invention will be more specifically described by way of Examples and Comparative Examples; however, the present invention is not limited to these Examples. Note that measurement methods employed in Examples are as follows.

(2) [Measurement of Solubility]

(3) Water (100 g) and a rotator were placed in a flask. The temperature of the flask was controlled to be 20? C. in a thermostat bath. The polymer (5 g) to be measured was charged in the flask and stirred for 12 hours or more. The resultant mixture was filtered by use of a filter (No. 5A) and dried at 60? C. until the whole filter reached a constant amount. Then, the weight of insoluble matter was weighed. The difference between the amount charged (5 g) and the weight of the insoluble matter was regarded as the solubility in water (100 g). If insoluble matter was not filtered out, the solubility was determined as 5 g or more; whereas if the difference between the amount charged (5 g) and the weight of insoluble matter was less than 0.1 g, the solubility was determined as less than 0.1 g, which means almost insoluble.

(4) [Measurement of Weight Average Molecular Weight]

(5) With the polymer to be measured, an eluent was blended to prepare a solution having a polymer concentration of 1.0 mg/mL. The solution was allowed to stand still overnight to dissolve the polymer and filtered by a 0.45-micron filter. The obtained filtrate was used as a sample. The weight average molecular weight of the polymer was determined by use of gel permeation chromatography in the following conditions.

(6) Data processing: Tosoh GPC-8020

(7) Apparatus: Tosoh HLC-8220GPC

(8) Column: Two columns of TSK gel Super AWM-H (6.0 mm ID?15 cm)

(9) Oven: 40? C.

(10) Eluent: 5 mmol/L LiBr in DMF (0.6 mL/min)

(11) Amount of sample: 40 ?L?1.0 mg/mL

(12) Detector: RI

(13) Calibration curve: Polystyrene (EasiCal (PS-1) manufactured by Agilent Technologies, Inc.)

(14) [Measurement of Content of Polymer in Separation Membrane]

(15) A blood processing apparatus was broken down to obtain a separation membrane. From the obtained separation membrane, 30 mg from the membrane pieces was dissolved in deuterated dimethylformamide so as to obtain a concentration of 5 mass %. The dissolution solution of the separation membrane was measured by a nuclear magnetic resonance apparatus in the following conditions to quantitatively determine the content of the polymer in the separation membrane.

(16) Measurement apparatus: Bruker Biospin Avance 600

(17) Nucleus to be observed: .sup.1H

(18) Observation frequency: 600 MHz

(19) Cumulated number: 1024 times

(20) A peak derived from a phenyl proton present at the ortho position of an ether bond in the vicinity of 7 ppm was used as a polysulfone peak; a peak derived from CH.sub.2 adjacent to N in the vicinity of 3.3 ppm as a polyvinylpyrrolidone peak; and a peak derived from an OH group in the vicinity of 5 ppm as a poly(hydroxypropyl methacrylate) peak to obtain integral intensities. From these, the contents in individual polymer components were obtained.

(21) [Measurement of Concentration of Polymer in Functional Separation Surface]

(22) A separation membrane was taken from a blood processing apparatus. When the blood processing apparatus was a hollow-fiber membrane module, one was taken from the center of a bundle of hollow-fiber membrane pieces, one from a portion of the outer circumference of the bundle and one from the opposite portion of the outer circumference. In total, three hollow-fiber membrane pieces were sampled. Measurement was performed at three points, i.e., center, and midpoints of the center and both ends of a single hollow-fiber membrane piece sampled in the fiber axis direction. In total, 9 points were measured. In each point, the separation membrane was cut along the fiber axis to expose the functional separation surface. The concentration of the polymer in the functional separation surface was measured by X-ray photoelectron spectroscopy in the following conditions. In the case where a wet membrane or a protecting agent was added, a hollow-fiber membrane was washed with pure water and lyophilized and then measurement was performed.

(23) Measurement apparatus: Thermo Fisher ESCALAB250

(24) Excitation source: Monochromatic AlK.sub.? 15 kV?10 mA

(25) Analysis size: About 1 mm

(26) Photoelectron escape angle: 0? (the axis of beam splitter is perpendicular to the surface of a sample)

(27) Pulse energy: 20 eV

(28) The concentration of the polymer in a functional separation surface was determined based on the ester group present in an acrylate polymer and a methacrylate polymer in accordance with the following procedure. The amounts of carbon, oxygen, nitrogen and sulfur were obtained respectively based on integrated intensities of C1s, O1s, N1s and S2p by use of relative sensitivity coefficients of elements (C1s: 1.00, O1s: 2. 72, N1s: 1.68, S2p: 1.98), as relative amounts (atomic %).

(29) Quantification of an ester group was performed by peak splitting of C1s, more specifically, by calculating the ratio of the peak area derived from an ester group relative to all elements (except hydrogen). This was determined as the amount of carbon derived from an ester group (atomic %). At this time, peak splitting of C1s was performed by five components: a component derived from CH, CC, C?C and CS bonds; a component derived from CO and CN bonds; a component derived from C?O (amide bond); a component derived from an ester group and a ?-?* shake up component. Furthermore, the amount of sulfur (atomic %) was used as an index of a polysulfone and the amount of nitrogen (atomic %) was used as an index of polyvinylpyrrolidone. When poly(hydroxypropyl methacrylate) was used as the polymer, the molecular weight of monomer was 144 and the concentration of the polymer in the functional separation surface was calculated from the following expression:
Concentration of polymer(mass %) in functional separation surface=(amount of carbon derived from an ester group?144/(amount of nitrogen?111+amount of sulfur?442+amount of carbon derived from an ester group?144))?100

(30) Where 111 is the molecular weight of polyvinylpyrrolidone monomer and 442 is the molecular weight of polysulfone monomer. The average value of the concentrations of the polymer at nine points in total was regarded as the average concentration of the polymer in the functional separation surface and a maximum value and a minimum value of the concentrations at the nine points were compared to the average concentration.

(31) When a polymer other than an acrylate polymer and a methacrylate polymer is used, calculation may be made from the peaks other than an ester group.

(32) [Ratio of Average Concentration of Polymer in Functional Separation Surface to Content of Polymer in Separation Membrane]

(33) The ratio of the average concentration of the polymer in a functional separation surface to the content of the polymer in a separation membrane was calculated from the aforementioned evaluation results in accordance with the following expression.
Ratio of average concentration of polymer in functional separation surface to content of polymer in separation membrane=concentration of polymer(mass %) in functional separation surface/content of polymer(mass %) in separation membrane
[Evaluation of Air-Bleeding During Priming]

(34) The case where a blood processing apparatus is a hollow fiber membrane-based module will be described. Lines were connected to each of a blood part and a dialyzed-fluid part. A port of the dialyzed-fluid part was plugged and an inlet port of the blood part was allowed to face down. In this state, physiological saline (Otsuka Normal Saline, manufactured by Otsuka Pharmaceutical Co., Ltd.) was supplied from the inlet port of the blood part at a rate of 100 mL/minute for 3 minutes, and the lines of the inlet port and outlet port of the blood part were stopped by use of forcipes. Subsequently, physiological saline was supplied from the port of a dialyzed-fluid part upward from the bottom at a rate of 500 mL/minute for one minute, and then, the lines of the inlet port and outlet port of the dialyzed-fluid part were stopped by use of forcipes. In this way, the blood processing apparatus was completely filled with physiological saline. Forcipes of the inlet port of the blood part and the outlet port of the dialyzed-fluid part were removed to allow the physiological saline to flow from the inlet port of the blood part through a filter (membrane) at a rate of 100 mL/minute. At this time, air bubbles in the physiological saline flowing toward the outlet port of the dialyzed-fluid part through the membrane were visually observed.

(35) The case where air bubbles disappear within one minute was evaluated as satisfactory and expressed by reference symbol ?; the case where air bubbles disappear within 3 minutes beyond one minute was expressed by reference symbol ?; and the case where 5 minutes or more was required until air bubbles disappear was evaluated as unsatisfactory and expressed by reference symbol x.

(36) [Measurement of Lactate Dehydrogenase (LDH) Activity]

(37) The blood compatibility of a separation membrane was evaluated based on adherability of platelets to a membrane surface and quantified based on the activity of lactate dehydrogenase contained in the platelets attached to the separation membrane.

(38) A blood processing apparatus was washed with physiological saline (Otsuka Normal Saline, manufactured by Otsuka Pharmaceutical Co., Ltd.). After priming, the blood processing apparatus was broken down and the separation membrane was taken out. The both ends of the separation membrane were processed with silicon such that an effective length was 15 cm and the area of an inner surface of the membrane was 5?10.sup.?3 m.sup.2 to fabricate a mini module.

(39) To the mini module, physiological saline (10 mL) was supplied to wash the insides of hollow fibers. Thereafter, human blood to which heparin was added (15 mL (heparin 1000 IU/L)), was circulated at a flow rate of 1.3 mL/min through the mini module prepared above at 37? C. for 4 hours. The inside and outside of the mini module were washed separately with physiological saline (10 mL). From the mini module thus washed, a half of all hollow-fiber membrane pieces of 7 cm in length were taken, cut into pieces, placed in a spitz type tube for LDH measurement and used as a measurement sample.

(40) Then, a 0.5 vol % Triton X-100/PBS solution (0.5 mL), which was obtained by dissolving Triton X-100 (manufactured by Nacalai Tesque, Inc.) in phosphate buffer (PBS) (manufactured by Wako Pure Chemical Industries, Ltd.), was added to the LDH measurement spitz pipe and treated with ultrasonic wave for 60 minutes to break the cells (primarily, platelets) attached to the hollow-fiber membrane. In this way, LDH in the cells was extracted. An aliquot (0.05 mL) was taken from the extract. To the aliquot, a 0.6 mM sodium pyruvate solution (2.7 mL) and a 1.277 mg/mL nicotinamide adenine dinucleotide (NADH) solution (0.3 mL) were added to react them. Immediately after the reaction, an aliquot (0.5 mL) was taken and the absorbance thereof was measured at 340 nm. The remaining liquid was further reacted at 37? C. for one hour and thereafter the absorbance thereof was measured at 340 nm. A reduction in absorbance from immediately after the reaction was determined. Absorbance of the membrane (blank), which was not reacted with blood, was measured in the same manner. The difference in absorbance was calculated in accordance with the following expression. In this method, the larger the reduction is, the higher the LDH activity is, more specifically, the larger the amount of platelets adhered to a membrane surface. Measurement was performed three times and an average value thereof was described as the difference in absorbance.
?340 nm=(absorbance of sample immediately after reaction?absorbance of sample after 60 minutes)?(absorbance of blank immediately after reaction?absorbance of blank after 60 minutes)
[Measurement of Amount of Elution]

(41) The eluted substances after a blood processing apparatus was fabricated (t=0) and the eluted substances from the apparatus stored at 60? C. for one month were compared based on UV and used as an index of storage stability.

(42) Based on the dialysis-based artificial kidney apparatus manufacturing approval standard, measurement was performed. From the blood processing apparatus, the separation membrane (1 g) was taken, soaked in pure water (100 mL) and extracted at 70? C. for one hour. The extract was used as a test liquid. Absorbance of the test liquid was measured at 220 to 350 nm by a spectrophotometer for ultraviolet and visible region.

Example 1

(43) As the polymer, poly(hydroxypropyl methacrylate) (PHPMA, manufactured by Aldrich Chemical Co.) was used. The solubility of the polymer in water (100 g) was less than 0.1 g and the weight average molecular weight thereof was 330,000.

(44) A polysulfone (PS) (P-1700, manufactured by Solvay S.A.) (17 parts by mass), a polyvinylpyrrolidone (PVP) (K-90, manufactured by BASF SE) (4 parts by mass) and dimethylacetamide (special-grade reagent, manufactured by Kishida Chemical Co., Ltd.) (79 parts by mass) were blended to prepare a spinning dope.

(45) A bore liquid was prepared by dissolving poly(hydroxypropyl methacrylate) in a 60 mass % aqueous dimethylacetamide solution so as to have a concentration of 0.03 mass %.

(46) From a tube-in-orifice type spinneret, the spinning dope and the bore liquid were ejected. At the time of ejection, the temperature of the spinning dope was 40? C. The ejected spinning dope was fed through a portion (drop portion) covered with a hood, soaked in a coagulation bath of 60? C. and coagulated therein. At this time, a spinning rate was set at 30 m/minute. A draft was 0.91. After washing with water and drying, a hollow separation membrane was obtained. Herein, water-washing was performed at a temperature of 90? C. for 180 seconds. The amounts of spinning dope and bore liquid ejected were controlled such that the thickness the membrane after dry became 35 ?m and the inner diameter became 185 ?m.

(47) From the obtained separation membrane, a module having an effective membrane area of 1.5 m.sup.2 was assembled and sterilized by application of an electron beam to obtain a blood processing apparatus.

(48) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory.

(49) The content of the polymer in the separation membrane was 0.19 mass %, the average concentration of the polymer in the functional separation surface was 34 mass %. A maximum concentration value of the polymer in the functional separation surface was 41 mass % and the minimum value thereof was 30 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of the polymer in the functional separation surface and the content of the polymer in the separation membrane was 179.

(50) The LDH activity was as good as 14 [?abs/hr/m.sup.2].

(51) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.041 and the absorbance after storage at 60? C. for one month was 0.044, which satisfied a standard value of 0.1 or less.

Example 2

(52) As the polymer, poly(hydroxyethyl methacrylate) (PHEMA, manufactured by Aldrich Chemical Co.) was used. The solubility of the polymer in water (100 g) was less than 0.1 g and the weight average molecular weight thereof was 1,700,000.

(53) The spinning dope described in Example 1 was used.

(54) A bore liquid was prepared by dissolving poly(hydroxyethyl methacrylate) in a 60 mass % aqueous dimethylacetamide solution so as to have a concentration of 0.01 mass %.

(55) From a tube-in-orifice type spinneret, the spinning dope and the bore liquid were ejected. At the time of ejection, the temperature of the spinning dope was 40? C. The ejected spinning dope was fed through a portion (drop portion) covered with a hood, soaked in a coagulation bath of 60? C. and coagulated therein. At this time, a spinning rate was set at 30 m/minute. A draft was 0.91. After washing with water and drying, a hollow separation membrane was obtained. Herein, water-washing was performed at a temperature of 90? C. for 180 seconds. The amounts of spinning dope and bore liquid ejected were controlled such that the thickness of the membrane after dry became 35 ?m and the inner diameter became 185 ?m.

(56) From the obtained separation membrane, a module having an effective membrane area of 1.5 m.sup.2 was assembled and sterilized by application of an electron beam to obtain a blood processing apparatus.

(57) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory.

(58) The content of the polymer in the separation membrane was 0.11 mass %, and the average concentration of the polymer in the functional separation surface was 21 mass %. A maximum concentration value of the polymer in the functional separation surface was 22 mass % and the minimum value thereof was 20 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of the polymer in the functional separation surface and the content of the polymer in the separation membrane was 191.

(59) The LDH activity was as good as 12 [?abs/hr/m.sup.2].

(60) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.035 and the absorbance after storage at 60? C. for one month was 0.041, which satisfied a standard value of 0.1 or less.

Example 3

(61) The polymer described in Example 2 was used.

(62) The spinning dope described in Example 1 was used.

(63) A bore liquid was prepared by dissolving poly(hydroxyethyl methacrylate) in a 60 mass % aqueous dimethylacetamide solution so as to have a concentration of 0.1 mass %.

(64) From a tube-in-orifice type spinneret, the spinning dope and the bore liquid were ejected. At the time of ejection, the temperature of the spinning dope was 40? C. The ejected spinning dope was fed through a portion (drop portion) covered with a hood, soaked in a coagulation bath of 60? C. and coagulated therein. At this time, a spinning rate was set at 30 m/minute. A draft was 0.91. After washed with water and dried, a hollow separation membrane was obtained. Herein, water-washing was performed at a temperature of 90? C. for 180 seconds. The amounts of spinning dope and bore liquid ejected were controlled such that the thickness of the membrane after dry became 35 ?m and the inner diameter became 185 ?m.

(65) From the obtained separation membrane, a module having an effective membrane area of 1.5 m.sup.2 was assembled.

(66) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory.

(67) The content of the polymer in the separation membrane was 0.60 mass %, and the average concentration of the polymer in the functional separation surface was 83 mass %. A maximum concentration value of the polymer in the functional separation surface was 90 mass % and the minimum value thereof was 79 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of the polymer in the functional separation surface and the content of the polymer in the separation membrane was 138.

(68) The LDH activity was as good as 16 [?abs/hr/m.sup.2].

(69) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.032 and the absorbance after storage at 60? C. for one month was 0.040, which satisfied a standard value of 0.1 or less.

Example 4

(70) The polymer described in Example 1 was used.

(71) A polyethersulfone (PES) (Sumikaexcel 4800P manufactured by Sumitomo Chemical Co., Ltd.) (17 parts by mass), a polyvinylpyrrolidone (K-90, Manufactured by BASF SE) (4 parts by mass) and dimethylacetamide (special-grade reagent, manufactured by Kishida Chemical Co., Ltd.) (79 parts by mass) were blended to prepare a spinning dope.

(72) A bore liquid was prepared by dissolving poly(hydroxypropyl methacrylate) in a 60 mass % aqueous dimethylacetamide solution so as to have a concentration of 0.03 mass %.

(73) From a tube-in-orifice type spinneret, the spinning dope and the bore liquid were ejected. At the time of ejection, the temperature of the spinning dope was 40? C. The ejected spinning dope was fed through a portion (drop portion) covered with a hood, soaked in a coagulation bath of 60? C. and coagulated therein. At this time, a spinning rate was set at 30 m/minute. A draft was 0.98. After washed with water and dried, a hollow separation membrane was obtained. Herein, water-washing was performed at a temperature of 90? C. for 180 seconds. The amounts of spinning dope and bore liquid ejected were controlled such that the thickness of the membrane after dry became 35 ?m and the inner diameter became 185 ?m.

(74) From the obtained separation membrane, a module having an effective membrane area of 1.5 m.sup.2 was assembled and sterilized by application of an electron beam to obtain a blood processing apparatus.

(75) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory.

(76) The content of the polymer in the separation membrane was 0.20 mass %, and the average concentration of the polymer in the functional separation surface was 36 mass %. A maximum concentration value of the polymer in the functional separation surface was 46 mass % and the minimum value thereof was 30 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of the polymer in the functional separation surface and the content of the polymer in the separation membrane was 180.

(77) The LDH activity was as good as 19 [?abs/hr/m.sup.2].

(78) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.039 and the absorbance after storage at 60? C. for one month was 0.046, which satisfied a standard value of 0.1 or less.

Example 5

(79) The polymer described in Example 1 was used.

(80) A polysulfone (P-1700, manufactured by Solvay S.A.) (17 parts by mass), a poly(vinyl pyrrolidone-vinyl acetate) (VA64, Luvitec VA64 manufactured by BASF SE) (4 parts by mass) and dimethylacetamide (special-grade reagent, manufactured by Kishida Chemical Co., Ltd.) (79 parts by mass) were blended to prepare a spinning dope.

(81) A bore liquid was prepared by dissolving poly(hydroxypropyl methacrylate) in a 60 mass % aqueous dimethylacetamide solution so as to have a concentration of 0.03 mass %.

(82) From a tube-in-orifice type spinneret, the spinning dope and the bore liquid were ejected. At the time of ejection, the temperature of the spinning dope was 40? C. The ejected spinning dope was fed through a portion (drop portion) covered with a hood, soaked in a coagulation bath of 60? C. and coagulated therein. At this time, a spinning rate was set at 30 m/minute. A draft was 0.95. After washed with water and dried, a hollow separation membrane was obtained. Herein, water-washing was performed at a temperature of 90? C. for 180 seconds. The amounts of spinning dope and bore liquid ejected were controlled such that the thickness of the membrane after dry became 35 ?m and the inner diameter became 185 ?m.

(83) From the obtained separation membrane, a module having an effective membrane area of 1.5 m.sup.2 was assembled and sterilized by application of an electron beam to obtain a blood processing apparatus.

(84) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory.

(85) The content of the polymer in the separation membrane was 0.16 mass %, and the average concentration of the polymer in the functional separation surface was 49 mass %. A maximum concentration value of the polymer in the functional separation surface was 57 mass % and the minimum value thereof was 43 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of the polymer in the functional separation surface and the content of the polymer in the separation membrane was 306.

(86) The LDH activity was as good as 21 [?abs/hr/m.sup.2].

(87) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.034 and the absorbance after storage at 60? C. for one month was 0.039, which satisfied a standard value of 0.1 or less.

Example 6

(88) As the polymer, a poly(hydroxyethyl methacrylate) (manufactured by Polymer Scientific Product) was used. The solubility of the polymer in water (100 g) was less than 0.1 g and the weight average molecular weight thereof was 200,000.

(89) The spinning dope described in Example 1 was used.

(90) A bore liquid was prepared by dissolving poly(hydroxyethyl methacrylate) in a 65 mass % aqueous dimethylacetamide solution so as to have a concentration of 0.05 mass %.

(91) From a tube-in-orifice type spinneret, the spinning dope and the bore liquid were ejected. At the time of ejection, the temperature of the spinning dope was 40? C. The ejected spinning dope was fed through a portion (drop portion) covered with a hood, soaked in a coagulation bath of 60? C. and coagulated therein. At this time, a spinning rate was set at 30 m/minute. A draft was 0.95. After washed with water and dried, a hollow separation membrane was obtained. Herein, water-washing was performed at a temperature of 90? C. for 180 seconds. The amounts of spinning dope and bore liquid ejected were controlled such that the thickness of the membrane after dry became 35 ?m and the inner diameter became 185 ?m.

(92) From the obtained separation membrane, a module having an effective membrane area of 1.5 m.sup.2 was assembled and sterilized by gamma ray to obtain a blood processing apparatus.

(93) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory.

(94) The content of the polymer in the separation membrane was 0.48 mass %, and the average concentration of the polymer in the functional separation surface was 48 mass %. A maximum concentration value of the polymer in the functional separation surface was 58 mass % and the minimum value thereof was 33 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of the polymer in the functional separation surface and the content of the polymer in the separation membrane was 100.

(95) The LDH activity was as good as 18 [?abs/hr/m.sup.2].

(96) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.033 and the absorbance after storage at 60? C. for one month was 0.040, which satisfied a standard value of 0.1 or less.

Example 7

(97) As the polymer, a poly(hydroxybutyl methacrylate) (PHBMA, manufactured by Polymer Scientific Product) was used. The solubility of the polymer in water (100 g) was less than 0.1 g and the weight average molecular weight thereof was 380,000.

(98) The spinning dope described in Example 1 was used.

(99) A bore liquid was prepared by dissolving poly(hydroxybutyl methacrylate) in a 60 mass % aqueous dimethylacetamide solution so as to have a concentration of 0.03 mass %.

(100) From a tube-in-orifice type spinneret, the spinning dope and the bore liquid were ejected. At the time of ejection, the temperature of the spinning dope was 40? C. The ejected spinning dope was fed through a portion (drop portion) covered with a hood, soaked in a coagulation bath of 60? C. and coagulated therein. At this time, a spinning rate was set at 30 m/minute. A draft was 0.91. After washed with water and dried, a hollow separation membrane was obtained. Herein, water-washing was performed at a temperature of 90? C. for 180 seconds. The amounts of spinning dope and bore liquid ejected were controlled such that the thickness of the membrane after dry became 35 ?m and the inner diameter became 185 ?m.

(101) From the obtained separation membrane, a module having an effective membrane area of 1.5 m.sup.2 was assembled and sterilized by application of a gamma beam to obtain a blood processing apparatus.

(102) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory.

(103) The content of the polymer in the separation membrane was 0.18 mass %, and the average concentration of the polymer in the functional separation surface was 33 mass %. A maximum concentration value of the polymer in the functional separation surface was 36 mass % and the minimum value thereof was 29 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of the polymer in the functional separation surface and the content of the polymer in the separation membrane was 183.

(104) The LDH activity was as good as 13 [?abs/hr/m.sup.2].

(105) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.030 and the absorbance after storage at 60? C. for one month was 0.039, which satisfied a standard value of 0.1 or less.

Comparative Example 1

(106) A blood processing apparatus was obtained in the same manner as in Example 1 except that a 60 mass % aqueous dimethylacetamide solution not containing the polymer was used as the bore liquid.

(107) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory. However, since the polymer was not contained, LDH activity was 398 [?abs/hr/m.sup.2]. Significant platelet adhesion was observed.

(108) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.034 and the absorbance after storage at 60? C. for one month was 0.133, which was beyond the standard value of 0.1. It was confirmed that the apparatus had no storage stability.

Comparative Example 2

(109) A blood processing apparatus was obtained in the same manner as in Example 1 except that a spinning dope containing a polysulfone (P-1700, manufactured by Solvay S.A.) (17 parts by mass) and dimethylacetamide (special-grade reagent, Kishida Chemical Co., Ltd.) (83 parts by mass) was used and a bore liquid, which was prepared by dissolving poly(hydroxypropyl methacrylate) in a 60 mass % aqueous dimethylacetamide solution so as to obtain a concentration of 0.1 mass % was used.

(110) Five minutes or more was required until air bubbles disappeared. Thus, air-bleeding was unsatisfactory.

(111) The content of the polymer in the separation membrane was 0.50 mass %, and the average concentration of the polymer in the functional separation surface was 73 mass %. A maximum concentration value of the polymer in the functional separation surface was 84 mass % and the minimum value thereof was 64 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the concentration of the polymer in the functional separation surface to the content of the polymer in the separation membrane was 146.

(112) The LDH activity was 398 [?abs/hr/m.sup.2]. Significant platelet adhesion was observed.

(113) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.007 and the absorbance after storage at 60? C. for one month was 0.010, which satisfied a standard value of 0.1 or less.

Comparative Example 3

(114) A blood processing apparatus was obtained in the same manner as in Example 1 except that a bore liquid prepared by dissolving poly(hydroxypropyl methacrylate) in a 60 mass % aqueous dimethylacetamide solution so as to obtain a concentration of 0.1 mass % was used, the spinning rate was set at 40 m/minute and the draft was set at 1.15.

(115) Air bubbles disappeared within three minutes. The air-bleeding was evaluated as ?.

(116) The content of the polymer in the separation membrane was 0.33 mass %, and the average concentration of the polymer in the functional separation surface was 28 mass %. A maximum concentration value of the polymer in the functional separation surface was 42 mass % and the minimum value thereof was 10 mass %. The maximum value and minimum value were outside the range of an average concentration?15%. The variation was large. The ratio of the average concentration of the polymer in the functional separation surface and the content of the polymer in the separation membrane was 85.

(117) The LDH activity was as good as 33 [? abs/hr/n12].

(118) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.029 and the absorbance after storage at 60? C. for one month was 0.069, which satisfied a standard value of 0.1 or less.

Comparative Example 4

(119) A blood processing apparatus was obtained in the same manner as in Example 1 except that a bore liquid prepared by dissolving poly(hydroxypropyl methacrylate) in a 75 mass % aqueous dimethylacetamide solution so as to obtain a concentration of 0.1 mass % was used, the spinning rate was set at 40 m/minute and the draft was set at 1.15.

(120) Air bubbles disappeared within three minutes. The air-bleeding was evaluated as ?.

(121) The content of the polymer in the separation membrane was 0.29 mass %, and the average concentration of the polymer in the functional separation surface was 13 mass %. A maximum concentration value of the polymer in the functional separation surface was 19 mass % and the minimum value thereof was 3 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of the polymer in the functional separation surface and the content of the polymer in the separation membrane was 45.

(122) The LDH activity was 348 [? abs/hr/m.sup.2]. Significant platelet adhesion was observed.

(123) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.039 and the absorbance after storage at 60? C. for one month was 0.088, which satisfied a standard value of 0.1 or less.

Comparative Example 5

(124) Poly(hydroxyethyl methacrylate) was obtained as follows.

(125) In a flask, ethanol (2600 g) was placed. Under a nitrogen atmosphere, hydroxyethyl methacrylate (Light Ester HO, manufactured by Kyoeisha Chemical Co., Ltd.) (2600 g) was added while stirring. Subsequently, Peroyl IPP (manufactured by NOF Corporation) (7 g) was added. Stirring was continued for 6 hours while controlling the temperature of the reaction solution to be 60? C. After 6 hours, water was added to terminate the reaction. The reaction product was dried under reduced pressure to obtain poly(hydroxyethyl methacrylate). The solubility of poly(hydroxyethyl methacrylate) in water (100 g) was 0.7 g and the weight average molecular weight thereof was 110,000.

(126) A blood processing apparatus was obtained in the same manner as in Example 1 except that a bore liquid prepared by dissolving poly(hydroxyethyl methacrylate) in a 15 mass % aqueous dimethylacetamide solution so as to obtain a concentration of 0.05 mass % was used, the spinning rate was set at 40 m/minute and the draft was set at 1.15.

(127) Air bubbles disappeared within three minutes. The air-bleeding was evaluated as ?.

(128) The content of poly(hydroxyethyl methacrylate) in the separation membrane was 0.20 mass % and the average concentration of poly(hydroxyethyl methacrylate) in the functional separation surface was 16 mass %. The maximum concentration value of poly(hydroxyethyl methacrylate) in the functional separation surface was 25 mass % and the minimum value thereof was 8 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of poly(hydroxyethyl methacrylate) in the functional separation surface to the content of poly(hydroxyethyl methacrylate) in the separation membrane was 80.

(129) The LDH activity was 329 [? abs/hr/m.sup.2]. Significant platelet adhesion was observed.

(130) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.031 and the absorbance after storage at 60? C. for one month was 0.145, which was beyond the standard value of 0.1. It was confirmed that the apparatus had no storage stability.

Comparative Example 6

(131) The polymer described in Example 1 was used.

(132) A polysulfone (P-1700, manufactured by Solvay S.A.) (17 parts by mass), a polyvinylpyrrolidone (K-90, manufactured by BASF SE) (4 parts by mass), poly(hydroxypropyl methacrylate) (0.5 parts by mass) and dimethylacetamide (special-grade reagent, manufactured by Kishida Chemical Co., Ltd.) (78.5 parts by mass) was blended to prepare a spinning dope.

(133) As a bore liquid, a 60 mass % aqueous dimethylacetamide solution not containing the polymer was used.

(134) From a tube-in-orifice type spinneret, the spinning dope and the bore liquid were ejected. At the time of ejection, the temperature of the spinning dope was 40? C. The ejected spinning dope was fed through a portion (drop portion) covered with a hood, soaked in a coagulation bath of 60? C. and coagulated therein. At this time, a spinning rate was set at 30 m/minute. A draft was 0.91. After washed with water and dried, a hollow separation membrane was obtained. Herein, water-washing was performed at a temperature of 90? C. for 180 seconds. The amounts of spinning dope and bore liquid ejected were controlled such that the thickness of the membrane after dry became 35 ?m and the inner diameter became 185 ?m.

(135) From the obtained separation membrane, a module having an effective membrane area of 1.5 m.sup.2 was assembled and sterilized by application of an electron beam to obtain a blood processing apparatus.

(136) Five minutes or more was required until air bubbles disappeared. Thus, air-bleeding was unsatisfactory.

(137) The content of the polymer in the separation membrane was 0.98 mass %, and the average concentration of the polymer in the functional separation surface was 21 mass %. A maximum concentration value of the polymer in the functional separation surface was 26 mass % and the minimum value thereof was 17 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of the polymer in the functional separation surface and the content of the polymer in the separation membrane was 21.

(138) The LDH activity was as good as 15 [? abs/hr/m.sup.2].

(139) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.030 and the absorbance after storage at 60? C. for one month was 0.038, which satisfied a standard value of 0.1 or less.

Comparative Example 7

(140) The spinning dope described in Example 1 was used.

(141) As a bore liquid, a 60 mass % aqueous dimethylacetamide solution not containing the was used.

(142) From a tube-in-orifice type spinneret, the spinning dope and the bore liquid were ejected. At the time of ejection, the temperature of the spinning dope was 40? C. The ejected spinning dope was fed through a portion (drop portion) covered with a hood, soaked in a coagulation bath of 60? C. and coagulated therein. At this time, a spinning rate was set at 30 m/minute. A draft was 0.91. After washed with water and dried, a hollow separation membrane was obtained. Herein, water-washing was performed at a temperature of 90? C. for 180 seconds. The amounts of spinning dope and bore liquid ejected were controlled such that the thickness of the membrane after dry became 35 ?m and the inner diameter became 185 ?m.

(143) From the obtained separation membrane, a module having an effective membrane area of 1.5 m.sup.2 was assembled.

(144) Poly(hydroxyethyl methacrylate) described in Example 6 was dissolved in a 40 mass % aqueous solution of ethanol so as to obtain a concentration of 0.2 mass % to prepare a coating liquid. The coating liquid (500 mL) was injected from a header cap having a nozzle for introducing (ejecting) a liquid at a 200 mL/minute. Excessive solution was removed by use of compressed air. Thereafter, drying was made under reduced pressure until a constant amount was obtained. After completion of drying, an electron beam was applied for sterilization to obtain a blood processing apparatus.

(145) Five minutes or more was required until air bubbles disappeared. Thus, air-bleeding was unsatisfactory.

(146) The content of the polymer in the separation membrane was 0.60 mass %, and the average concentration of the polymer in the functional separation surface was 55 mass %. The maximum concentration value of the polymer in the functional separation surface was 73 mass % and the minimum value thereof was 38 mass %. The maximum value and minimum value were outside the range of an average concentration?15%. The variation was large. The ratio of the average concentration of the polymer in the functional separation surface to the content of the polymer in the separation membrane was 92.

(147) The LDH activity was as good as 13 [? abs/hr/m.sup.2].

(148) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.031 and the absorbance after storage at 60? C. for one month was 0.040, which satisfied a standard value of 0.1 or less.

Comparative Example 8

(149) In place of the polymer, poly(hydroxyethyl acrylate) (PHEA, manufactured by Scientific Polymer Product) was used. The solubility of poly(hydroxyethyl acrylate) in water (100 g) was 5 g or more and the weight average molecular weight thereof was 260,000.

(150) A blood processing apparatus was obtained in the same manner as in Example 1 except that a bore liquid prepared by dissolving poly(hydroxyethyl acrylate) in a 60 mass % aqueous dimethylacetamide solution so as to obtain a concentration of 0.1 mass %.

(151) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory.

(152) The content of poly(hydroxyethyl acrylate) in the separation membrane was 0.40 mass % and the average concentration of poly(hydroxyethyl acrylate) in the functional separation surface was 45 mass %. The maximum concentration value of poly(hydroxyethyl acrylate) in the functional separation surface was 51 mass % and the minimum value thereof was 42 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of poly(hydroxyethyl acrylate) in the functional separation surface to the content of poly(hydroxyethyl acrylate) in the separation membrane was 113.

(153) The LDH activity was 378 [? abs/hr/m.sup.2]. Significant platelet adhesion was observed.

(154) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.042 and the absorbance after storage at 60? C. for one month was 0.140, which was beyond the standard value of 0.1. It was confirmed that the apparatus had no storage stability.

Comparative Example 9

(155) As the polymer having a hydroxy group at an end, polyethylene glycol (PEG, manufactured by Wako Pure Chemical Industries, Ltd.) was used. The solubility of polyethylene glycol in water (100 g) was 5 g or more and the weight average molecular weight thereof was 560,000.

(156) A blood processing apparatus was obtained in the same manner as in Example 1 except that a bore liquid prepared by dissolving polyethylene glycol in a 60 mass % aqueous dimethylacetamide solution so as to obtain a concentration of 0.1 mass %.

(157) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory.

(158) The content of polyethylene glycol in the separation membrane was 0.33 mass % and the average concentration of polyethylene glycol in the functional separation surface was 41 mass %. The maximum concentration value of polyethylene glycol in the functional separation surface was 48 mass % and the minimum value thereof was 37 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of polyethylene glycol in the functional separation surface to the content of polyethylene glycol in the separation membrane was 124.

(159) The LDH activity was 384 [? abs/hr/m.sup.2]. Significant platelet adhesion was observed.

(160) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.034 and the absorbance after storage at 60? C. for one month was 0.110, which was beyond the standard value of 0.1. It was confirmed that the apparatus had no storage stability.

Comparative Example 10

(161) In place of the polymer, Styleze 2000 (manufactured by ISP) was used. Styleze 2000 is a copolymer constituted of vinylpyrrolidone, an acrylic acid and lauryl methacrylate. Since suspended insoluble matter in water was not successfully filtered out, it was impossible to measure the solubility in water (100 g). The weight average molecular weight was 980,000.

(162) A blood processing apparatus was obtained in the same manner as in Example 1 except that a bore liquid prepared by dissolving Styleze 2000 in a 60 mass % aqueous dimethylacetamide solution so as to obtain a concentration of 0.1 mass %.

(163) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory.

(164) The content of Styleze 2000 in the separation membrane was 0.42 mass % and the average concentration of the polymer in the functional separation surface was 49 mass %. The maximum concentration value of Styleze 2000 in the separation membrane was 54 mass % and the minimum value thereof was 42 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of Styleze 2000 in the functional separation surface to the content of Styleze 2000 in the separation membrane was 117.

(165) The LDH activity was as good as 23 [? abs/hr/m.sup.2].

(166) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.046 and the absorbance after storage at 60? C. for one month was 0.105, which was beyond the standard value of 0.1. It was confirmed that the apparatus had no storage stability.

Comparative Example 11

(167) In place of the polymer, poly(vinyl pyrrolidone-vinyl acetate) (manufactured by Wako Pure Chemical Industries, Ltd.) was used. The solubility of poly(vinyl pyrrolidone-vinyl acetate) in water (100 g) was 2.1 g and the weight average molecular weight thereof was 51,000.

(168) A blood processing apparatus was obtained in the same manner as in Example 1 except that a bore liquid prepared by dissolving poly(vinyl pyrrolidone-vinyl acetate) in a 60 mass % aqueous dimethylacetamide solution so as to obtain a concentration of 0.1 mass % was used.

(169) Air bubbles disappeared within one minute. Thus, air-bleeding was satisfactory.

(170) The content of poly(vinyl pyrrolidone-vinyl acetate) in the separation membrane was 0.37 mass % and the average concentration of poly(vinyl pyrrolidone-vinyl acetate) in the functional separation surface was 36 mass %. The maximum concentration value of poly(vinyl pyrrolidone-vinyl acetate) in the functional separation surface was 46 mass % and the minimum value thereof was 30 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of poly(vinyl pyrrolidone-vinyl acetate) in the functional separation surface to the content of poly(vinyl pyrrolidone-vinyl acetate) in the separation membrane was 97.

(171) The LDH activity was as good as 28 [? abs/hr/m.sup.2].

(172) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.058 and the absorbance after storage at 60? C. for one month was 0.133, which was beyond the standard value of 0.1. It was confirmed that the apparatus had no storage stability.

Comparative Example 12

(173) Poly(hydroxyethyl methacrylate) described in Comparative Example 5 was used.

(174) A blood processing apparatus was obtained in the same manner as in Example 1 except that a bore liquid prepared by dissolving poly(hydroxyethyl acrylate) in a 60 mass % aqueous dimethylacetamide solution so as to obtain a concentration of 10 mass % was used.

(175) Five minutes or more was required until air bubbles disappeared. Thus, air-bleeding was unsatisfactory.

(176) The content of poly(hydroxyethyl methacrylate) in the separation membrane was 32 mass %, and the average concentration of poly(hydroxyethyl methacrylate) in the functional separation surface was 100 mass %. The maximum concentration value of poly(hydroxyethyl methacrylate) in the functional separation surface was 100 mass % and the minimum value was 98 mass %. The maximum value and minimum value fell within the range of an average concentration?15%. The variation was small. The ratio of the average concentration of poly(hydroxyethyl methacrylate) in the functional separation surface to the content of poly(hydroxyethyl methacrylate) in the separation membrane was 3.

(177) The LDH activity was 268 [? abs/hr/m.sup.2]. Significant platelet adhesion was observed.

(178) The amount of elution was evaluated. As a result, the absorbance after the treatment apparatus was prepared was 0.044 and the absorbance after storage at 60? C. for one month was 0.055, which was beyond the standard value of 0.1. It was confirmed that the apparatus had no storage stability.

(179) TABLE-US-00001 TABLE 1 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Polysulfone PS PS PS PES PS PS PS polymer Hydrophilic PVP PVP PVP PVP VA64 PVP PVP polymer Polymer having a Poly(hydroxy- Poly(hydroxy- Poly(hydroxy- Poly(hydroxy- Poly(hydroxy- Poly(hydroxy- Poly(hydroxy- hydroxy group propyl ethyl ethyl propyl propyl ethyl butyl methacrylate) methacrylate) methacrylate) methacrylate) methacrylate) methacrylate) methacrylate) PHPMA PHEMA PHEMA PHPMA PHPMA PHEMA PHBMA Solubility less than 0.1 g less than 0.1 g less than 0.1 g less than 0.1 g less than 0.1 g less than 0.1 g less than 0.1 g Weight average 330,000 1,700,000 1,700,000 330,000 330,000 200,000 380,000 molecular weight (Mw) Added to Bore liquid Bore liquid Bore liquid Bore liquid Bore liquid Bore liquid Bore liquid Addition 0.03 mass % 0.01 mass % 0.1 mass % 0.03 mass % 0.03 mass % 0.05 mass % 0.03 mass % concentration (300 ppm) (100 ppm) (1000 ppm) (300 ppm) (300 ppm) (500 ppm) (300 ppm) Draft 0.91 0.91 0.91 0.98 0.95 0.95 0.91 Content [A] of 0.19 mass % 0.11 mass % 0.60 mass % 0.20 mass % 0.16 mass % 0.48 mass % 0.18 mass % polymer Average surface 34 mass % 21 mass % 83 mass % 36 mass % 49 mass % 48 mass % 33 mass % concentration [B] of polymer Maximum value 41 mass % 22 mass % 90 mass % 46 mass % 57 mass % 58 mass % 36 mass % Minimum value 30 mass % 20 mass % 79 mass % 30 mass % 43 mass % 33 mass % 29 mass % [B]/[A] 179 191 138 180 306 100 183 Air-bleeding ? ? ? ? ? ? ? LDH activity 14 12 16 19 21 18 13 UV value at t = 0 0.041 0.035 0.032 0.039 0.034 0.033 0.030 UV value after one 0.044 0.041 0.040 0.046 0.039 0.040 0.039 month at 60? C.

(180) TABLE-US-00002 TCBLE 2 Comparative Comparative Comparative Comparative Comparative Comparative Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Polysulfone polymer PS PS PS PS PS PS Hydrophilic polymer PVP PVP PVP PVP PVP Polymer having a Poly(hydroxypropyl Poly(hydroxypropyl Poly(hydroxypropyl Poly(hydroxyethyl Poly(hydroxypropyl hydroxy group methacrylate) methacrylate) methacrylate) methacrylate) methacrylate) PHPMA PHPMA PHPMA PHEMA PHPMA Solubility less than 0.1 g less than 0.1 g less than 0.1 g 0.7 g less than 0.1 g Weight average 330,000 330,000 330,000 110,000 330,000 molecular weight (Mw) Added to Bore liquid Bore liquid Bore liquid Bore liquid Dope Addition concentration 0.1 mass % 0.1 mass % 0.1 mass % 0.05 mass % 0.5 mass % (1000 ppm) (1000 ppm) (1000 ppm) (500 ppm) Draft 0.91 0.91 1.15 1.15 1.15 0.91 Content [A] of polymer 0.50 mass % 0.33 mass % 0.29 mass % 0.20 mass % 0.98 mass % Average surface 73 mass % 28 mass % 13 mass % 16 mass % 21 mass % concentration [B] of polymer Maximum value 84 mass % 42 mass % 19 mass % 25 mass % 26 mass % Minimum value 64 mass % 10 mass % 3 mass % 8 mass % 17 mass % [B]/[A] 146 85 45 80 21 Air-bleeding ? X ? ? ? X LDH activity 398 393 33 348 329 15 UV value at t = 0 0.034 0.007 0.029 0.039 0.031 0.030 UV value after one 0.133 0.010 0.069 0.088 0.145 0.038 month at 60? C.

(181) TABLE-US-00003 TABLE 3 Comparative Comparative Comparative Comparative Comparative Comparative Example 7 Example 8 Example 9 Example 10 Example 11 Example 12 Polysulfone polymer PS PS PS PS PS PS Hydrophilic polymer PVP PVP PVP PVP PVP PVP Polymer having a hydroxy Poly(hydroxypropyl Poly(hydroxyethyl Polyethylene Styleze2000 Poly(vinyl Poly(hydroxyethyl group methacrylate) acrylate) glycol pyrrolidone-vinyl methacrylate) PHPMA PHEA PEG acetate) PHEMA Solubility less than 0.1 g 5 g or more 5 g or more Unmeasurable 2.1 g 0.7 g Weight average molecular 200,000 260,000 560,000 980,000 51,000 110,000 weight (Mw) Added to Coating liquid Bore liquid Bore liquid Bore liquid Bore liquid Bore liquid Addition concentration 0.2 mass % 0.1 mass % 0.1 mass % 0.1 mass % 0.1 mass % 10 mass % (2000 ppm) (1000 ppm) (1000 ppm) (1000 ppm) (1000 ppm) Draft 0.91 0.91 0.91 0.91 0.91 0.91 Content [A] of polymer 0.60 mass % 0.40 mass % 0.33 mass % 0.42 mass % 0.37 mass % 32 mass % Average surface 55 mass % 45 mass % 41 mass % 49 mass % 36 mass % 100 mass % concentration [B] of polymer Maximum value 73 mass % 51 mass % 48 mass % 54 mass % 46 mass % 100 mass % Minimum value 38 mass % 42 mass % 37 mass % 42 mass % 30 mass % 98 mass % [B]/[A] 92 113 124 117 97 3 Air-bleeding X ? ? ? ? X LDH activity 13 378 384 23 28 268 UV value at t = 0 0.031 0.042 0.034 0.046 0.058 0.044 UV value after one month at 0.040 0.140 0.110 0.105 0.133 0.055 60? C.

(182) The present application is based on a Japanese patent application (Japanese Patent Application No. 2011-242260) filed on Nov. 4, 2011, the content of which is incorporated herein by reference.

INDUSTRIAL APPLICABILITY

(183) The present invention can provide a separation membrane for blood processing having not only excellent substance removal performance but also blood compatibility as well as storage stability, also with satisfactory air-bleeding during priming treatment of the separation membrane for blood processing, and provide a blood processing apparatus having the membrane installed therein. Therefore, the present invention has industrial applicability as a separation membrane to be used in an extracorporeal-circulation blood purification therapy.