JPH1147567A - Separation membrane and its preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a separation membrane which has high substance permeability and less adhesion of blood ingredients by making a polyalkylene glycol being water-insolubilized exist on at least part of the surface of the separation membrane at a specified ratio. SOLUTION: To obtain a separation membrane which is built in a device for hemocatharsis and has both high substance permeability and anti- thrombocyte adhesiveness, a water-insoluble polyalkylene glycol is made to exist on the surface of the separation membrane at a ratio of 0.01 ng/cm<2> -500 ng/cm<2> . In this case, the separation membrane is formed by using at least one resin selected from polysulfone resins, polymethacrylate resins, polyacrylonitriles, polyamides, etc., as a base material. Under a condition where this separation membrane base material is immersed in a polyalkylene glycol soln. or is brought into contact with it, it is irradiated with radiation beams. In addition, under a condition where the separation membrane base material is assembled into a module and the separation membrane base material is immersed in a polyalkylene glycol soln. or is brought into contact with it, it is irradiated with radiation beams to prepare a device for hemocatharsis in which the separation membrane is built.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a separation membrane having both high substance permeation performance and antiplatelet adhesion and a blood purifier including the same.

[0002]

2. Description of the Related Art At present, various polymer materials are used in the medical field, but artificial blood vessels, catheters, blood bags,
In tools that come into direct contact with blood, such as artificial kidneys, the adhesion of blood components such as plasma proteins and platelets and the formation of thrombus resulting therefrom are inevitable problems. Particularly, in the case of a separation membrane used for blood purification, the adhesion of blood components directly leads to a decrease in the performance of the membrane, which is an important problem.

[0003] Conventionally, materials for separation membranes for blood purification include cellulose, cellulose acetate, cellulose triacetate, polyolefin, polyimide, polycarbonate, polyarylate, polyester, polyacrylonitrile, polymethyl methacrylate, polyamide, and polysulfone resin. High molecular compounds have been used.
Among them, in particular, polyolefin, polyimide, polycarbonate, polyarylate, polyester, polyacrylonitrile, polymethyl methacrylate, polysulfone resin, etc., due to the hydrophobicity of the material itself, blood components, especially due to adhesion of plasma proteins and platelets Performance degradation over time was inevitable. As means for hydrophilizing the hydrophobic film to solve the drawbacks of the hydrophobic film, for example, Japanese Patent Publication No.
Although a medical material grafted in the range of 100 μg / cm2 is shown, such means is useful in imparting antithrombotic properties to an artificial blood vessel or the like, but a water-soluble polymer is used in a separation membrane. Since the pores are closed or reduced, the performance is deteriorated, which is not preferable. In addition, JP-A-6-
No. 2,288,872 discloses a hollow fiber membrane in which a hydrophilic polymer substance insolubilized in water is physically held on the surface. However, it has not been possible to achieve both high blood compatibility and high substance permeation performance. Not in. That is, to date, a separation membrane having both high substance permeability and blood compatibility has not been realized.

[0004]

DISCLOSURE OF THE INVENTION The present inventor aims to improve the prior art by providing a separation membrane having a high substance permeability and less adhesion of blood components such as plasma proteins and platelets, and such a separation membrane. An object of the present invention is to provide a blood purifier having built-in blood compatibility, particularly antiplatelet adhesion.

[0005]

In order to achieve the above object, the present invention has the following arrangement. (1) A separation membrane characterized in that a water-insoluble polyalkylene glycol is present on at least a part of the surface at a rate of 0.01 ng / cm2 or more and 500 ng / cm2 or less.

(2) A blood purifier comprising the separation membrane according to the above (1).

(3) The method for producing a separation membrane, wherein the substrate is irradiated with radiation while the base material of the separation membrane is immersed in or in contact with the polyalkylene glycol solution.

(4) A blood purification system incorporating the separation membrane, wherein the separation membrane substrate is incorporated in a module, and the separation membrane substrate is irradiated with radiation while being immersed or in contact with the polyalkylene glycol solution. Method of manufacturing the vessel.

[0009]

DETAILED DESCRIPTION OF THE INVENTION In the present invention, polymer compounds such as cellulose, cellulose acetate, cellulose triacetate, polyolefin, polyimide, polycarbonate, polyarylate, polyester, polyacrylonitrile, polymethyl methacrylate, polyamide, and polysulfone resin are used. The main component, the effect is exhibited in the separation membrane further using it as a base material, among which, in particular,
It is particularly remarkably exhibited in a separation membrane having a polysulfone resin, a polymethacrylic acid resin, a polyacrylonitrile, a polyamide, and a cellulose resin.

[0010] The blood purifier in the present invention is a module containing a separation membrane for blood treatment, such as a hemodialyzer, a hemofilter, a hemofiltration dialyzer, and a plasma separator.

The polyalkylene glycol in the present invention is a chain polymer containing an oxygen atom in the main chain represented by, for example, polyethylene glycol or polypropylene glycol, but may be a polymer grafted with polyalkylene glycol.

The water-insoluble polyalkylene glycol is in the range of 0.01 to 500 ng / cm 2, preferably 0.05 to 500 ng / cm 2.
It must be insolubilized in the range of 300 ng / cm2 and exist on the surface of the separation membrane. If the immobilization density of polyalkylene glycol is low, the degree of antiplatelet adhesion is low, and if the immobilization density is high, a gel layer of polyalkylene glycol is formed on the membrane surface, , The material permeability tends to decrease. In addition, 200ng / c
Densities below m2 and below 10 ng / cm2 can also be selected.

The degree of insolubilization of the polyalkylene glycol (hereinafter sometimes referred to as immobilization density) is extremely low as compared with the conventional treatment method for the purpose of making the material surface hydrophilic. The conventional method is to fix a relatively large amount of hydrophilic polymer on the surface of a material and make the material hydrophilic by coating the surface of the material. Such a method is effective for blood circuits and blood bags, for example. However, when applied to a separation membrane for blood treatment, a gel layer of a hydrophilic polymer is formed on the membrane surface, and therefore, it is not possible to suppress the adhesion of blood components such as plasma proteins and platelets. Even if it is possible, it is difficult to maintain the original material permeation performance of the membrane. In contrast, in the present invention, by setting the proportion of polyalkylene glycol in the range of 0.01 to 500 ng / cm2, the detailed mechanism is unknown, but for example, the polyalkylene glycol forms a gel layer on the film surface. Without forming, the inherent motility of polyalkylene glycol, in other words, the elimination volume effect, suppresses the contact of blood components with the membrane surface, expresses high antiplatelet adhesion, and maintains high substance permeation performance We think that we can do.

The water-insoluble polyalkylene glycol is a polyalkylene glycol which is physically and / or chemically immobilized on the surface of a separation membrane, and has an effective membrane area of 1 m ² (based on the inner surface in the case of a hollow fiber membrane). 37
When immersed in 1 L of distilled water at 1 ° C. for 1 hour, the polyalkylene glycol eluted in distilled water is 1 mg or less. The amount of the polyalkylene glycol eluted in distilled water is 1 mg or less when immersed in 1 L of 37 ° C. distilled water for 1 hour per 1 m ² per 1 m ² of the effective membrane area of the separation membrane (in the case of hollow fiber membrane, based on the inner surface). Means the amount of polyalkylene glycol remaining after washing until the

In order to immobilize the polyalkylene glycol on the membrane surface, a conventionally known method can be used, and conditions may be adjusted so that the immobilization density is in the above-mentioned range. For example, in the case of a method using radiation, radiation may be applied while the separation membrane substrate is immersed in or brought into contact with a polyalkylene glycol solution (preferably an aqueous solution). What is necessary is just to be insolubilized with respect to. When a blood purifier such as a hemodialyzer, a hemofilter, a hemofiltration dialyzer, and a plasma separator containing a separation membrane is made to have antiplatelet adhesion, the separation membrane and at least the blood in the blood purifier are used. If radiation treatment is performed while the polyalkylene glycol aqueous solution is in contact with all the parts that come into contact, not only the surface of the membrane but also all the parts that come into contact with blood, such as the end of the blood purifier and the inside of the header, have antiplatelet adhesion. It is also possible to reduce blood clotting at the end of the blood purifier.

In the above method, the molecular weight of the polyalkylene glycol and the concentration of the aqueous solution of the polyalkylene glycol in the solution are not particularly limited, and the desired degree of antiplatelet adhesion and the amount of the separation membrane with respect to the aqueous solution of the polyalkylene glycol are not limited. , An optimal condition can be selected. For example, in general, the degree of antiplatelet adhesion is relatively low for a combination of low molecular weight and low concentration, and the degree of antiplatelet adhesion is higher as the molecular weight is higher or the concentration is higher. Also, by increasing the molecular weight of the polyalkylene glycol even at a low concentration, or conversely, by increasing the aqueous solution concentration even at a low molecular weight polyalkylene glycol, the immobilized density of the polyalkylene glycol on the membrane surface increases, The degree of platelet adhesion is increased. However, in the treatment method of the present invention, by selecting the molecular weight of the polyalkylene glycol, the concentration of the aqueous solution becomes 1
Sufficient antiplatelet adhesion can be obtained even at a relatively low concentration of up to 5,000 ppm, so that not only the cost for antiplatelet adhesion can be kept low, but also a blood purification device containing a separation membrane can be used in a blood purification device. In the case of performing radiation treatment by filling with an alkylene glycol aqueous solution, it is possible to even eliminate washing of the blood purifier after the treatment, which is preferable.
On the other hand, when the combination of high molecular weight and high concentration is used, not only the polyalkylene glycol chains are immobilized on the membrane surface, but also the polyalkylene glycol chains cross-link with each other to form a gel layer on the membrane surface, The pores of the separation membrane can be easily closed, and the material permeability may be reduced.

The optimum conditions for the relationship between the molecular weight of the polyalkylene glycol and the concentration of the aqueous solution of the polyalkylene glycol differ depending on the material of the separation membrane to be made antiplatelet-adhering, its shape, pore size, and the like.

For example, in the case of a polysulfone hollow fiber separation membrane used for a hemodialyzer, a relatively low molecular weight polyalkylene glycol having a number average molecular weight of about 200 is used.
At a concentration lower than ppm, high anti-platelet adhesion cannot be expected. Conversely, with a relatively high molecular weight polyalkylene glycol having a molecular weight of about 20,000, a decrease in substance permeability tends to occur at a concentration of 50,000 ppm or more. From the above, in the case of the polysulfone hollow fiber separation membrane, the product of the molecular weight of the polyalkylene glycol and the concentration of the aqueous solution (ppm) is preferably 10 ⁴ or more and 10 ⁷ or less. Also,
If it is a polymethyl methacrylate hollow fiber separation membrane used for a hemodialyzer, the molecular weight or aqueous solution of a polyalkylene glycol which can be expected to have an effect of antiplatelet adhesion compared to the case of the polysulfone hollow fiber separation membrane described above. The concentration is relatively high, and a polyalkylene glycol having a molecular weight of 1000 requires an aqueous solution concentration of 1000 ppm or more, and a molecular weight of 6000 requires an aqueous solution concentration of 100 ppm or more. Furthermore, even a high-concentration aqueous solution having a concentration of 2000 ppm or more of a relatively high-molecular-weight polyalkylene glycol having a molecular weight of about 20,000 can be suitably used without a decrease in substance permeability. From the above, in the case of the polymethyl methacrylate hollow fiber separation membrane, the product of the molecular weight of the polyalkylene glycol and the concentration of the aqueous solution (ppm) is preferably 10 ⁶ or more, and on the other hand, 10 ⁹ or less. In the case of a polyacrylonitrile hollow fiber separation membrane, a remarkable effect is not seen at a relatively low molecular weight and at a low concentration.
If the molecular weight is 6000 ppm or more and the molecular weight is 6000, the concentration is 1000p
Above pm, the antiplatelet adhesion effect appears. That is, in the case of the polyacrylonitrile hollow fiber separation membrane, the product of the molecular weight of the polyalkylene glycol and the concentration of the aqueous solution (ppm) is preferably 10 ⁶ or more and 10 ⁹ or less. Similarly to the polyacrylonitrile hollow fiber separation membrane, the polyamide hollow fiber separation membrane has no effect when the molecular weight is relatively low and the concentration is low.
If the concentration is 00, the effect of anti-platelet adhesion appears at a concentration of 500 ppm or more, and the suitable conditions for the aqueous solution are almost the same as those for the polyacrylonitrile hollow fiber separation membrane. On the other hand, in the case of a cellulosic resin hollow fiber separation membrane, the effect is exhibited even in a combination of a relatively low molecular weight and a low concentration.
Even if the concentration is 0, the concentration is 500 ppm or more, and if the molecular weight is 1,000, the effect of antiplatelet adhesion appears at a concentration of 500 ppm or more. That is, in the case of the cellulose resin hollow fiber separation membrane, the product of the molecular weight of the polyalkylene glycol and the concentration of the aqueous solution (ppm) is preferably 10 ⁴ or more and 10 ⁹ or less.

The irradiation dose of radiation is not particularly limited, provided that the irradiation dose is such that the polyalkylene glycol chains are immobilized on the surface of the membrane to be made antiplatelet-adherent or the blood contact surface of the blood purifier. Good, preferably 10 to 50 kGy as absorption energy, more preferably 15 to 4 kGy
About 0 kGy is preferably used. In addition, sterilization can be performed simultaneously with imparting antiplatelet adhesion.

[0020]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below based on embodiments.

Hereinafter, the measuring method used is as follows.

(1) Measurement of immobilized density of polyethylene glycol The mini-module (or small module) after irradiation was disassembled, and the hollow fiber was taken out.
^It was immersed in 1 L of distilled water at 37 ° C. for 1 hour for 2 hours, and washed while exchanging water until the amount of PEG eluted in distilled water became 1 mg or less. Washed hollow fiber at 50 ° C, 0.5 torr
For 10 hours. 10-100 mg of dried hollow fiber
Was placed in a test tube, 2 ml of a mixed solution of acetic anhydride and paratoluenesulfonic acid was added, the mixture was acetylated at 120 ° C. for about 1 hour, and after cooling, the wall was washed off with 2 ml of pure water, and then 20%
The mixture was neutralized with a sodium carbonate solution, extracted with 5 ml of trichloromethane, and analyzed by gas chromatography (hereinafter referred to as GC).

The amount of polyethylene glycol immobilized on the membrane was determined from a previously prepared calibration curve.

The immobilization density per unit surface area was determined by dividing the amount of immobilization determined by GC by the surface area including the inside of the pores of the membrane determined by the nitrogen adsorption method.

(2) In vitro Platelet Adhesion Experiment The blood inlet and dialysate outlet of the mini-module after irradiation were connected with a silicon tube, and distilled water 500
After the hollow fiber and the inside of the module were washed by flowing 100 ml / min at a flow rate of 100 ml / min, rabbit fresh blood 1 containing 10% by volume of a 3.8% aqueous sodium citrate solution was added to the hollow fiber hollow portion.
0 cc was flowed at 0.57 ml / min, washed with physiological saline, fixed with glutaraldehyde, and the hollow fiber separation membrane was cut out from the mini-module and freeze-dried. The inner surface of this hollow fiber
Observation was performed with a FE-SEM (field emission scanning electron microscope), and the number of adhered platelets in an area of 0.01 cm 2 was counted.

(3) In Vivo Platelet Adhesion Experiment The blood inlet and dialysate outlet of the small module after irradiation were connected with a silicon tube, and 100 mL of distilled water was passed through the blood outlet.
After washing the hollow fiber and the inside of the module by flowing 0 ml at a flow rate of 100 ml / min, blood drawn from the carotid artery of a rabbit weighing about 3 kg is passed through the hollow fiber hollow through the blood inlet of the small module and the blood outlet of the small module. An extracorporeal circulation test was performed to return the rabbit to the jugular vein of the rabbit. The blood flow rate is 50ml
/ Min, initial administration of heparin as an anticoagulant 18 IU,
Circulation was continued for 3 hours while continuously administering 60 IU / hr. After the end of extracorporeal circulation, the cells were washed with physiological saline and fixed with glutaraldehyde in the same manner as in the in vitro platelet adhesion experiment, and the hollow fiber cut out from the module and the module header were freeze-dried. The inner surface of the hollow fiber and the inside of the module header (blood contact surface) were observed by FE-SEM, and the number of adhered platelets in an area of 0.01 cm 2 was counted.

(4) Measurement of β2-microglobulin (β2-MG) removal performance in vitro The blood inlet and the dialysate outlet of the mini-module after irradiation were connected with a silicon tube, and distilled water 500 from the blood outlet.
After the hollow fiber and the inside of the module were washed by flowing 100 ml / min at a flow rate of 100 ml / min, the bovine serum was subjected to a filter treatment.
In 0 ml, human β2-MG was dissolved at a concentration of 5 mg / ml, and perfused into the hollow portion of the hollow fiber in the mini-module at 1 ml / min, and 140 ml of PBS kept at 37 ° C. was added to the outside of the hollow fiber at 20 ml / min.
Perfusion in closed form at a speed of. After perfusion for 4 hours
The outer perfusate was collected and the clearance was calculated. The clearance was calculated by equation (2).

(Equation 1) Where CL: clearance (ml / min), CBi: concentration at the module inlet (mg / ml), CBo: concentration at the module outlet (mg / m)
l), QB: Module supply liquid volume (ml / min).

The sample hollow fibers used in Examples and Comparative Examples were prepared as follows.

Examples 1 to 12 and Comparative Example 1 20 parts of polysulfone (Udel P-3500) and 2 parts of water were added to 78 parts of N, N-dimethylacetamide and dissolved by heating. This membrane-forming stock solution was discharged from an orifice-type double cylindrical die, passed through the air 200 mm, and then guided into a coagulation bath of 100% water to obtain a hollow fiber. At this time, DMAc5
An injection liquid of 0 parts and 50 parts of water was used. The inner diameter of the hollow fiber was 0.2 mm, and the film thickness was 0.04 mm.

The polysulfone hollow fiber separation membranes thus prepared were bundled in a bundle of 40, and both ends were fixed to a glass tube module case with an epoxy potting agent so as not to block the hollow portion of the hollow fiber. Created a mini module. The mini-module has a diameter of about 7 mm and a length of about 10 cm.

The blood inlet and the dialysate outlet of the mini-module are connected by a silicon tube, and 100 ml of a polyethene glycol aqueous solution is flowed from the blood outlet at a flow rate of 100 ml / min.
The mini-module was capped to prevent air from entering, and irradiated with γ-rays at 30 kGy. The molecular weight and aqueous solution concentration of polyethylene glycol in the aqueous polyethylene glycol solution filled in the mini-module are shown in the table. Using the mini-module thus prepared, the measurement of the immobilized density of polyethylene glycol, the in vitro platelet adhesion experiment, and the in vitro β2-MG removal performance were measured.
The measurement results of each mini-module are shown in the table as relative values when the results of Comparative Example 1 in which distilled water was filled and γ-rays were irradiated were set to 100.

Examples 13 to 21, Comparative Example 2 iso (isotactic) -polymethyl methacrylate 5
Parts, syn (syndiotactic) -polymethyl methacrylate (20 parts) was added to dimethyl sulfoxide (75 parts) and dissolved by heating. This membrane-forming stock solution was discharged from an orifice-type double cylindrical die, passed through the air 200 mm, and then guided into a coagulation bath of 100% water to obtain a hollow fiber. At this time, dry nitrogen was used as the internal injection gas. The inner diameter of the hollow fiber was 0.2 mm, and the film thickness was 0.03 mm.

Using the polymethyl methacrylate hollow fiber separation membrane prepared in this manner, a mini-module was prepared in the same manner as in Example 1, filled with distilled water or various polyethyne glycol aqueous solutions, and subjected to γ-ray irradiation at 30 kGy. Was irradiated.
The molecular weight and aqueous solution concentration of polyethylene glycol in the aqueous polyethylene glycol solution filled in the mini-module are shown in the table. Using the mini-module prepared in this way, measurement of the immobilized density of polyethylene glycol, in
An in vitro platelet adhesion experiment and in vitro β2-MG removal performance were measured. The measurement results of each mini-module are shown in the table as relative values, where the results of Comparative Example 2 in which distilled water was filled and γ-ray irradiation was performed were set to 100.

Example 22, Comparative Example 3 A dialyzer "PAN-17DX" manufactured by Asahi Medical Co., Ltd. was disassembled, and a hollow fiber separation membrane (made of polyacrylonitrile) was cut out.

Using this hollow fiber separation membrane, a mini-module was prepared in the same manner as in Example 1, and distilled water and a molecular weight of 60 were prepared.
A polyethene glycol aqueous solution having a concentration of 2000 ppm was filled and irradiated with γ-rays at 30 kGy. Using the mini-module prepared in this way, measurement of the immobilized density of polyethylene glycol, in vitro platelet adhesion experiment, and measurement of in vitro β2-MG removal performance were performed. The measurement results of each mini-module are shown in the table as relative values, where the results of Comparative Example 3 in which distilled water was filled and γ-ray irradiation was performed were set to 100.

Example 23, Comparative Example 4 Dialyzer "Polyflux-16" manufactured by Gambro
0 "was disassembled, and a hollow fiber separation membrane (made of polyamide) was cut out.

Using this hollow fiber separation membrane, a mini-module was prepared in the same manner as in Example 1, and distilled water and a molecular weight of 60 were prepared.
A polyethylene glycol aqueous solution having a concentration of 2000 ppm was filled and irradiated with 30 kGy γ-rays. Using the mini-module prepared in this way, measurement of the immobilized density of polyethylene glycol, in vitro platelet adhesion experiment, and measurement of in vitro β2-MG removal performance were performed. Example 2
Table 3 shows the measurement results of Comparative Example 3 as relative values with the result of Comparative Example 4 in which distilled water was filled and γ-ray irradiation was performed, where 100.

Example 24, Comparative Example 5 A dialyzer "MC-1.5H" manufactured by Izumi Kogyo Kagaku was dismantled.
A hollow fiber separation membrane (hemophane) was cut out.

Using this hollow fiber separation membrane, a mini-module was prepared in the same manner as in Example 1, and distilled water and a molecular weight of 60 were prepared.
A polyethylene glycol aqueous solution having a concentration of 2000 ppm was filled and irradiated with 30 kGy γ-rays. Using the mini-module prepared in this way, measurement of the immobilized density of polyethylene glycol, in vitro platelet adhesion experiment, and measurement of in vitro β2-MG removal performance were performed. Example 2
Table 4 shows the measurement results of Comparative Example 4 as relative values, where the result of Comparative Example 5 in which distilled water was filled and γ-ray irradiation was performed was taken as 100.

Example 25, Comparative Example 6 3,500 hollow polysulfone hollow fiber separation membranes spun in the same manner as in Example 1 were bundled, and both of the hollow fiber separation membranes were coated with a urethane-based potting agent so as not to block the hollow fiber hollow portion. The ends were fixed to a polystyrene module case, and polystyrene module headers were attached to both ends of the module case, thereby producing a small module shown in FIG. The small module has a body diameter of about 3 cm and a length of about 15 cm.
The blood inlet and dialysate outlet of this small module are connected by a silicon tube, and distilled water or molecular weight 6
500 ml of an aqueous solution of polyethyne glycol having a concentration of 2000 ppm and 2000 ppm was flowed at a flow rate of 100 ml / min. The small module was capped so that air did not enter the module, and irradiated with γ rays at 30 kGy. Measurement of the immobilized density of polyethylene glycol using the small module prepared in this way,
An in vivo platelet adhesion experiment was performed. After washing the similarly treated small module, the module was disassembled and the hollow fiber was taken out, a mini-module similar to that of Example 1 was prepared, and the in vitro β2-MG removal performance was measured. Comparative Example 6 wherein the measurement result of Example 25 was filled with distilled water and irradiated with gamma rays.
The results are shown in the table as relative values with the result being 100.

Example 26, Comparative Example 7 3,500 polymethyl methacrylate hollow fiber separation membranes spun in the same manner as in Example 10 were bundled, and a small module was prepared in the same manner as in Example 18; Filled with distilled water or an aqueous solution of polyethyne glycol having a molecular weight of 6000 and a concentration of 2000 ppm was irradiated with γ-rays at 30 kGy. Using the small module prepared in this way, the immobilization density of polyethylene glycol was measured, and an in vivo platelet adhesion experiment was performed. After washing the similarly treated small module, a mini-module was prepared in the same manner as in Example 25, and the in vitro β2-MG removal performance was measured. The measurement results of Example 26 are shown in the table as relative values, where the results of Comparative Example 7 in which distilled water was filled and γ-ray irradiation was performed were set to 100.

[0042]

[Table 1]

[0043]

[Table 2]

[0044]

[Table 3]

[0045]

[Table 4]

[0046]

[Table 5]

[0047]

[Table 6]

[0048]

[Table 7]

As can be seen from the results of Examples 1 to 26, by immobilizing a specific amount of water-insoluble polyethylene glycol on the membrane surface, the number of adherent platelets is reduced, and the antiplatelet adhesion is improved. Furthermore, as can be seen from the results of Examples 25 and 26, since the number of platelets adhered to the inner surface of the header is also reduced, it can be seen that antiplatelet adhesion can be achieved on the entire blood contact surface of the blood purifier. Also, β2-MG
It can be seen that the removal ability almost maintains the performance of the separation membrane in which polyethylene glycol is not insolubilized on the membrane surface, and there is almost no decrease in the substance permeation performance.

Example 27 A small module after irradiation with γ-ray treated in the same manner as in Example 25 was disassembled and a hollow fiber was taken out.
It was dried at 0.5 torr for 10 hours. 20g of dried hollow fiber
Was added to 200 ml of DMAc and stirred at room temperature for 2 hours.
MAc insolubles were filtered off. This DMAc insoluble matter is transferred to a new DMA
c 200 ml was added again, and the mixture was stirred at room temperature for 2 hours. This operation was repeated three times, and the DMAc insoluble matter obtained was washed with distilled water and dried at 50 ° C. and 0.5 torr for 10 hours. The dried insoluble matter was subjected to IR measurement by the KBr method. At the same time, 10 to 100 mg of the insoluble matter was placed in a test tube, and 2 ml of a mixed solution of acetic anhydride and paratoluenesulfonic acid was added.
Acetylation at about 1 hour, cool down, wash the vessel wall with 2 ml of pure water, neutralize with 20% sodium carbonate solution,
Extracted with 5 ml of trichloromethane and analyzed by GC.

As a result of IR measurement, the measurement chart shows that the absorption at 1585 cm-1 derived from the benzene ring of polysulfone, the absorption at 1150 cm-1 derived from the sulfonyl group, and the absorption at 1690 cm-1 derived from the tertiary amide group of polyvinylpyrrolidone were obtained. Was observed. GC
As a result, a peak derived from polyethylene glycol was observed. From the above results, it was found that the polysulfone, polyvinylpyrrolidone, and polyethylene glycol were mutually cross-linked by irradiating the polysulfone membrane containing polyvinylpyrrolidone with gamma rays in an aqueous polyethylene glycol solution.

Example 28 A small module after irradiation with gamma rays treated in the same manner as in Example 26 was disassembled, and a hollow fiber was taken out. The hollow fiber was replaced with methylene chloride instead of DMAc. The same operation as in Example 27 was performed except that the measurement was not performed, and an IR measurement and a GC measurement were performed on the insoluble portion of methylene chloride. As a result of IR measurement, the measurement chart shows that the polymethyl methacrylate is derived from a carboxylic acid ester of 1740 cm.
Absorption of -1 was observed. From the results of GC, a peak derived from polyethylene glycol was observed. From the above results, it was found that polymethyl methacrylate and polyethylene glycol crosslinked each other by irradiating the polymethyl methacrylate film with gamma rays in an aqueous solution of polyethylene glycol.

[0053]

As described above, the separation membrane according to the present invention is a separation membrane having high antiplatelet adhesion and high material permeation performance, and the separation membrane can be easily obtained at low cost. it can.

[Brief description of the drawings]

FIG. 1 is a schematic view of a mini-module used in Examples 1 to 24 of the present invention and Comparative Examples 1 to 5.

FIG. 2 is a schematic diagram of a small module used in Examples 25 and 26 of the present invention and Comparative Examples 6 and 7.

[Explanation of symbols]

 1. Blood inlet 2. Potting section 3. Dialysate inlet 4. Hollow fiber separation membrane 5. Glass tube module case 6. Dialysate inlet 7. Blood outlet 8. Module header 9. Module case

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI B01D 71/66 B01D 71/66 D01C 1/00 D01C 1/00

Claims (7)

[Claims] 1. A separation membrane characterized in that a water-insoluble polyalkylene glycol is present on the surface at a rate of 0.01 ng / cm 2 or more and 500 ng / cm 2 or less. 2. The method according to claim 1, wherein the water-insoluble polyalkylene glycol is present in an amount of from 0.1 to 2.
2. The separation membrane according to claim 1, wherein the separation membrane is present at a rate of not less than 05 ng / cm2 and not more than 300 ng / cm2. 3. The separation membrane according to claim 1, wherein said separation membrane comprises at least one resin selected from the group consisting of a polysulfone resin, a polymethacrylic acid resin, a polyacrylonitrile, a polyamide and a cellulose resin. film. 4. The separation membrane according to claim 1, which is for blood purification. 5. A blood purifier incorporating the separation membrane according to claim 4. 6. The method for producing a separation membrane according to claim 1, wherein the substrate is immersed in or contacted with a polyalkylene glycol solution and irradiated with radiation. 7. The separation according to any one of claims 1 to 4, wherein the separation membrane substrate is incorporated in a module, and the separation membrane substrate is irradiated with radiation while being immersed or in contact with the polyalkylene glycol solution. Manufacturing method of blood purifier with built-in membrane.