JP4937699B2 - Blood purifier and method for producing the same - Google Patents

Description

  The present invention relates to a blood purifier for use in the treatment of renal diseases or drug addiction, in particular hemodialysis therapy, hemofiltration dialysis therapy, or blood filtration therapy, and a method for producing the same.

Conventionally, semipermeable membranes and ultrafiltration membranes are used for hemodialysis therapy, hemofiltration dialysis therapy, hemofiltration therapy and the like (hereinafter referred to as blood purification therapy).
Examples of membranes used in this blood purification therapy (semi-permeable membranes and ultrafiltration membranes) include cellulose, cellulose ester, polyacrylonitrile, polymethyl methacrylate, polyvinyl alcohol, ethylene-vinyl alcohol copolymer, polyamide, polysulfone, polyester, A polyester polymer alloy or the like is used.

In blood purification therapy, generally, a hollow fiber bundle obtained by spinning the above-described membrane into a hollow fiber shape (hereinafter referred to as a hollow fiber membrane) is bundled in a casing with a hollow fiber bundle of about 5000 to 10,000 hollow fibers. In addition to the use of blood purifiers constructed by loading them, recently, blood purifiers constructed by loading the above-described membranes in the form of beads into casings have also been proposed.
For example, in a blood purifier using a hollow fiber membrane, uremic substances can be removed by filtration by flowing blood to the inner surface side of the hollow fiber membrane as blood filtration therapy, or the inner surface side of the hollow fiber membrane as hemodialysis therapy. In addition, blood is allowed to flow through and the dialysate is allowed to flow on the outer surface side, and the blood and dialysate are brought into contact with each other through a hollow fiber membrane to remove uremic substances by diffusion and remove excess water in the body. . In the blood purifier, the characteristics of both hemofiltration therapy and hemodialysis therapy are removed as hemofiltration dialysis therapy, that is, uremic substances and excess water in the body are removed by filtration and diffusion.

  Such hollow fiber membranes are roughly classified into hydrophilic membranes typified by cellulose and hydrophobic membranes typified by polysulfone and polyester, and their mechanical strength, heat resistance, chemical resistance, Hydrophobic membranes are widely used as hollow fiber membranes for blood purification therapy because of their good biocompatibility.

  In this hydrophobic membrane, since it is hydrophobic, the original permeability cannot be immediately exhibited, and in order to immediately exhibit the original permeability, a treatment for imparting hydrophilicity to the hydrophobic membrane in advance is performed. Is going. The blood purifier using this hydrophobic hollow fiber membrane has a wet type that is filled with water to make it wet, and water is filled inside the blood purifier when used. There are dry-type ones that are activated (rewet), and in any case, a treatment for imparting hydrophilicity is required. In particular, the dry type is advantageous in that it is light in weight and free from fear of freezing. When used, it is activated (re-wetted) with a physiological saline solution.

As a treatment for imparting hydrophilicity, for example, a method in which polyvinylpyrrolidone as a hydrophilic polymer is mixed into a stock solution of a polysulfone-based resin that is a hydrophobic polymer, and this solution is spun as a film-forming stock solution. Has been proposed (Patent Document 1, Patent Document 2).
In addition, a spun hollow fiber membrane is dipped in a treatment liquid containing a membrane permeability maintaining agent (hydrophilic agent) and then dried to form a hollow fiber bundle.

Examples of membrane permeability maintaining solution (hydrophilic treatment solution) include glycerin aqueous solution, polyvinyl pyrrolidone aqueous solution, polyethylene glycol aqueous solution, ethanol, etc., but easy handling and low cost, and when using a hollow fiber module If importance is given to the fact that the hydrophilizing agent is difficult to elute into the blood, an aqueous glycerin solution is used.
Japanese Patent Publication No. 5-54373 JP-A-7-289863

In the method of spinning or beading from the membrane-forming stock solution mixed with the hydrophilic polymer, hydrophilicity is imparted over the produced hollow fiber membrane and the inner and outer surfaces of the beads and in the entire thickness direction, and In this method, mixing the hydrophilic polymer into the spinning dope also has the purpose of forming the membrane structure and the fine structure of the beads, so that the hydrophilic polymer must be mixed in a certain amount or more.
For this reason, elution of the hydrophilic polymer mixed in from the hollow fiber membrane after spinning occurs, and if this hollow fiber membrane is used as it is in the blood purifier, the hydrophilic polymer eluted in the patient's body will enter. There is a risk that.

In addition, when a blood purifier is constructed using a hollow fiber bundle that has been hydrophilized with glycerin, the component (urethane residue) of the resin composition is not cured when it is adhesively fixed to the casing body with a sealing material. It may react with glycerin in the state.
For this reason, the end of the hollow fiber bundle needs to be cut and removed together with the sealing material, and then thoroughly washed away with the cleaning liquid, leaving room for improvement in improving the production efficiency of the blood purifier (hollow fiber type module).

  The present invention has been made in view of the above problems, and can absorb moisture in a short time during activation (rewetting) to return to a wet state, and the leaked hydrophilizing agent migrates into the patient's body. An object of the present invention is to provide a blood purifier capable of preventing this and a method for manufacturing the same.

To achieve the above object, the one described in claim 1 of the present invention, with a carrier for purification such as a hollow fiber membrane or beads of a hydrophobic polymer having adsorbability was Material In blood purifiers,
The blood purifier is characterized in that trehalose and polyvinylpyrrolidone are adhered and held on the blood contact portion of the carrier for the purifier.

The pump of Claim 2, the amount of the trehalose allowed to adhere held in the carrier is blood purification according to claim 1, characterized in that the 10mg~10g per square meter of the blood contact part of the carrier It is a vessel.

Those described in claim 3, wherein the hydrophobic polymer is a blood purifier according to claim 1 or claim 2 and a polyester resin and a polysulfone-based resin, characterized in that as the Material.

What is described in claim 4 is a step of producing a bundle of hollow fiber membranes made of a hydrophobic polymer,
Storing the bundle of hollow fiber membranes in a cylindrical casing, and sealing and sealing between the blood contact portion and the dialysate contact portion; and
And a step of bringing trehalose and polyvinylpyrrolidone into contact with the blood contact portion side of the module and then drying and adhering and holding the module.

Those described in claim 5 is a front Symbol manufacturing method of a blood purifier of claim 4, characterized in that it comprises a step of holding the crosslinked trehalose by irradiation with polyvinylpyrrolidone.

According to the present invention, the following excellent effects can be obtained.
According to the invention of claim 1, the blood purifier having a carrier for purification such as a hollow fiber membrane or beads of a hydrophobic polymer having adsorbability was Material, the purifier Trehalose and polyvinylpyrrolidone are attached and held on the blood contact part of the carrier, so that the carrier for purification such as hollow fiber membranes or beads is trehalose which is a saccharide having a high water retention function and polyvinyl which is a hydrophilic polymer. By adhering and holding pyrrolidone on the blood contact portion, hydrophilicity can be imparted while eliminating the use of a hydrophilic polymer or reducing the amount used. As a result, it is possible to eliminate or reduce the hydrophilic polymer from being eluted into the patient's body. Moreover, by using saccharides, protein aggregation (formation of β-sheet) in blood can be suppressed, and progress of dialysis amyloidosis can be suppressed. In addition, the SOD (superoxide dismutase: enzyme that scavenges active oxygen) activity in the blood can be stabilized, and problems caused by active oxygen generated during dialysis can be reduced. Furthermore, by suppressing the complement (c3a, c5a, etc.) in the blood by the action of the hydroxyl group (OH group) of the saccharide, an inhibitory effect on autoimmune diseases can be expected.

According to the invention of claim 2 , since the amount of the trehalose adhered and held on the carrier is 10 mg to 10 g per square meter of the blood contact portion of the carrier, hydrophilicity can be reliably imparted.

According to the invention of claim 3, wherein the hydrophobic polymer, since a polyester resin and a polysulfone-based resin is a Material, while adsorbing the hydrophilic polymer to the blood contact portion side surface, blood noncontact It is possible to leave a high level of adsorptive power for substances (such as endotoxin) that are undesirable for the human body on the surface side. As a result, it is possible to achieve a higher level of conventional contradictory functions of preventing blood components from adhering to the membrane surface and preventing the invasion of defective substances into the body.

According to invention of Claim 4 , the process of producing the bundle | flux of the hollow fiber membrane which consists of hydrophobic polymer, the bundle | flux of the said hollow fiber membrane is accommodated in a cylindrical casing, and also a blood contact part and dialysate A module comprising: a step of sealing between the contact portions to form a module; and a step of bringing trehalose and polyvinylpyrrolidone into contact with the blood contact portion side of the module and then drying and adhering and holding the module. The hydrophilizing agent can be attached and retained by simply contacting at least the blood sugar contact portion with trehalose, which is a saccharide, and polyvinylpyrrolidone, which is a hydrophilic polymer, and drying it.
In addition, there is no need to provide a special process separately, and the spinning process of the hollow fiber membrane and the process of modularization can use existing equipment, reduce investment in manufacturing equipment, and reduce the cost of the blood purifier. Can be provided.

According to the invention described in claim 5 , since the polyvinyl pyrrolidone is configured to include the step of holding the trehalose by crosslinking by irradiation with radiation , the polyvinyl pyrrolidone that is a hydrophilic polymer is irradiated with radiation. It is possible to produce a blood purifier that is hydrophilic on the carrier surface and can contain trehalose , which is a saccharide, in the network structure, improving the retention of saccharides and increasing hydrophilicity. it can.

Embodiments of the present invention will be described below with reference to the drawings.
FIG. 1 is a flowchart showing a schematic process of a blood purifier having a hollow fiber bundle according to an embodiment of the method for producing a blood purifier of the present invention.

In this manufacturing process, as shown in the flowchart of FIG. 1, the hollow fiber is first spun (spinning process, step S1).
In this spinning step, a film forming stock solution is first prepared. Here, the mixing weight ratio (A / B) of the polyester resin (A) and the polysulfone resin (B) is determined in the range of 0.1 to 10, and the total amount (A + B) of both resins is 10% by weight. A film forming stock solution is prepared by dissolving in an organic solvent so that the ratio is ˜25 wt%.

  In addition, the said polyester-type resin in this embodiment is a polyarylate resin which has a repeating unit represented by following Formula (1), and the said polysulfone-type resin is a repeating unit represented by following Formula (2), and the following. It is a polysulfone resin having at least one of the repeating units represented by the formula (3).

  Further, the organic solvent is not particularly limited as long as it is a good solvent for the polyester resin and the polysulfone resin, and for example, N-methylpyrrolidone, tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, and the like can be used. . Of these, N-methylpyrrolidone can be most preferably used.

A hollow fiber membrane can be produced by discharging this membrane-forming stock solution into the coagulation solution together with the core solution using a double tube spinneret.
Here, the core solution and the coagulation solution are for forming the membrane-forming stock solution into a hollow fiber membrane, but a mixed solvent obtained by mixing an organic solvent used for resin dissolution with water is preferable to water alone. . This is because it is easier to form a uniform fibril structure when a mixed solvent is used. As the organic solvent to be mixed, a good solvent for the resin, for example, N-methylpyrrolidone, tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide and the like can be used. Of these, N-methylpyrrolidone can be most preferably used.

  The hollow fiber membrane thus spun has a dense layer formed on its inner surface and a porous layer so as to cover the outside of the dense layer. In the hollow fiber membrane, the dense layer is a portion that defines the selective permeability and permeation rate of the substance, and pores having an average pore diameter of less than 500 angstroms, specifically, pores having a pore radius of 30 to 100 angstroms are formed. ing. Further, the porous layer functions as a support layer that supports the dense layer and maintains the strength of the film, and pores that are considerably coarser than the dense layer are formed.

  The hollow fiber membrane thus obtained has the molecular weight fractionation characteristics shown in FIG. 2. For example, for a material having a molecular weight of 35,000, the sieve coefficient (SC) is about 0.5, that is, the total amount is about 50. % Of the substance having a molecular weight of 70,000, the sieve coefficient is about 0.05, that is, about 5% of the total amount permeates the hollow fiber membrane and the remaining about 95% cannot penetrate. I understand. Similarly, a substance having a molecular weight of 100,000 or more cannot pass through almost the entire amount (100%).

Next, the hollow fiber membranes thus spun are bundled (bundling process step, step S2).
In this bundling process, a bundle is formed in which about 10,000 hollow fiber membranes are formed into one bundle. The bundle of hollow fiber membranes (hereinafter referred to as hollow fiber bundle) is adjusted to an outer diameter corresponding to the inner diameter of the cylindrical casing.

Next, the hollow fiber bundle is loaded into the casing of the blood purifier (loading step, step S3).
As shown in the cross-sectional view of FIG. 3, the blood purifier 1 according to the present invention includes a casing 2, an injection-side blood port cap member 3 that functions as a closing lid member that is detachably screwed to the casing 2, and The discharge side blood port cap member 4 and a hollow fiber bundle 10 loaded in the casing 2 are schematically configured.

  The casing 2 is a cylindrical member formed of polycarbonate, and constitutes a case in combination with the above-described injection-side blood port cap member 3 and discharge-side blood port cap member 4. A dialysate inflow port 5 is formed on the side surface of the casing 2 on the discharge side blood port cap member 4 side, and the dialysate discharge port is formed on the end portion on the injection side blood port cap member 3 side. An outlet 6 is formed.

  The injection-side blood port cap member 3 and the discharge-side blood port cap member 4 are screwed together so as to close the openings at both ends of the casing 2, and are formed of polycarbonate as in the casing 2. The injection side blood port cap member 3 is provided with an injection port 7 for injecting blood, and the discharge side blood port cap member 4 is provided with a discharge port 8 for discharging blood. Yes. In addition, O-rings 9 are disposed at the contact portions of the injection-side blood port cap member 3 and the discharge-side blood port cap member 4 and the casing 2 as sealing materials for maintaining watertightness.

  In this loading step, the above-described hollow fiber bundle 10 is loaded into the casing 2 in a state where the injection-side blood port cap member 3 and the discharge-side blood port cap member 4 are detached. At this time, in order to prevent the hollow fiber bundle 10 from being contaminated and to facilitate loading, the outer periphery of the hollow fiber bundle 10 is previously covered with a sheet, and the entire sheet is loaded into the casing 2. Then, after loading, the sheet is extracted. In addition, in a state where the hollow fiber bundle 10 is loaded, both end portions of the hollow fiber bundle 10 are in a state of protruding outside the casing 2.

Next, potting is performed (potting process, step S4).
In this potting process, as shown in FIG. 3, the opening 11 of the casing 2 is sealed (sealed) with a urethane-based resin 12 as a sealing material, and the portion of the hollow fiber bundle 10 that protrudes outside the casing is Cut so as to be flush with the opening 11 of the casing 2. Thereby, a module in which the hollow fiber bundle 10 is loaded in the casing 2 is created.
As shown in FIG. 4, the cut surface of the hollow fiber bundle 10 is in a state where a large number of hollow fiber membranes 13 whose ends are open are densely packed, and the urethane resin 12 is a gap between the hollow fiber membranes 13. Since the urethane resin 12 does not block the inflow port 5 and the outflow port 6 of the dialysate, the blood flow channel is used in this module. (The inner surface 13 ′ side of the hollow fiber membrane 13) and the dialysate flow path (the outer surface side of the hollow fiber membrane 13) are separated by the hollow fiber membrane 13.

Next, a hydrophilic treatment is performed (hydrophilic treatment step, step S5).
This hydrophilization treatment step is the most important step of the present invention, and at least uses saccharides to adhere and hold the carrier for purification of the blood purifier (regardless of the shape of the hollow fiber membrane, bead-like membrane, etc.). Processing is performed. That is, in this hydrophilization treatment, only a saccharide having a high water retention function is used as a hydrophilizing agent, or a hydrophilic polymer is mixed with the saccharide to eliminate the use of a conventional hydrophilic polymer. Reduce.
Thus, it is possible to prevent or suppress the hydrophilic polymer from being eluted from the blood purifier during the blood purification therapy and moving into the patient's body as much as possible.
In addition, the use of the disaccharide trehalose as a saccharide can be expected to have an effect of suppressing protein amyloidation, and may delay the onset of dialysis amyloidosis caused by amyloidation of β2-microglobulin in blood. I can expect.

As the hydrophilizing agent used for the hydrophilization treatment, monosaccharides or disaccharides are used as saccharides having a high water retention function. For example, glucose or the like is used as monosaccharides and trehalose or the like is used as disaccharides. The saccharide can be selected from the group consisting of trehalose, glucose, fructose, galactose, maltose, sucrose, cellobiose, and lactose. The hydrophilic polymer used by mixing with these saccharides can be selected from the group consisting of, for example, polyvinylpyrrolidone, polyethylene glycol, polyglycol monoester, polypropylene glycol copolymer, and polyacrylamide.
However, in this hydrophilization treatment, an aqueous solution of a hydrophilic polymer mixed with saccharides is allowed to flow to the blood contact portion side in the module, whereby blood contact on the carrier surface of the module or the blood port cap members 3 and 4 It is used to increase the retention rate of sugars on the surface on the part side. In other words, by using a part of the hydrophilic polymer and then irradiating with radiation, the hydrophilic polymer is cross-linked on the surface of the carrier, and the retention rate is increased by encapsulating saccharides in the network structure. Is desirable.
This eliminates the use of conventional hydrophilic polymers and reduces the amount used.

Therefore, the hydrophilic polymer is required to have the property of not permeating the hollow fiber membrane 13 and the property of having a strong adsorptive power to the blood contact portion, and these properties are defined by the molecular weight. In general, it is known that a water-soluble polymer (that is, a hydrophilic polymer) adsorbs one molecule at a number of adsorption points, and the higher the molecular weight, the stronger the adsorbing power and the higher the molecular weight As the size of the molecule increases, it becomes difficult to penetrate the hollow fiber membrane 13.
Therefore, as the hydrophilic polymer used in this hydrophilization treatment step, pores having an average pore diameter of less than 500 angstroms formed on the inner surface 13 ′ side (that is, the dense layer) of the hollow fiber membrane 13 are blocked without passing therethrough. Moreover, those having a molecular weight that has an adsorbing force of a predetermined strength with respect to the inner surface 13 ′ of the hollow fiber membrane 13 are suitable.

  Then, if a polymer having a non-permeability of 95% or more of the hollow fiber membrane 13 is suitable (that is, a polymer having a molecular weight of 70,000 or more) Although considered, for the purpose of hydrophilizing only the surface of the blood contact portion, a polymer having a molecular weight of 100,000 or more is more preferable (see FIG. 2), and for example, the finding that polyvinylpyrrolidone is most suitable is obtained.

  The hydrophilization treatment step using such a hydrophilizing agent includes, for example, the injection-side blood port cap member 3 and the both ends of the module (that is, the casing 2 loaded with the hollow fiber bundle 10) made of a hollow fiber membrane carrier. With the discharge-side blood port cap member 4 attached, an aqueous solution of a hydrophilizing agent adjusted to a predetermined concentration was injected from the injection port 7 of the injection-side blood port cap member 3 and passed through the blood contact portion side in the module. The aqueous solution of the hydrophilizing agent is discharged from the discharge port of the discharge side blood port cap member 4. By performing this treatment for several tens of seconds to several tens of minutes, the hydrophilizing agent is applied to blood such as the inner surface 13 ′ of the hollow fiber membrane 13, the inner surfaces of the two blood port cap members 3, 4, or the surface of the urethane resin 12. By drying the contact portion in a wet state, the saccharide is adhered and held on the carrier. The amount of saccharide adhering to the carrier is desirably 10 mg to 10 g, more desirably 50 to 1000 mg per square meter of the blood contact portion of the carrier.

Further, in this hydrophilization treatment, when an aqueous solution of a hydrophilic polymer is mixed with saccharides and flowed to the blood contact part side in the module, the hydrophilizing agent is used as the inner surface 13 ′ of the hollow fiber membrane 13 or both blood. After the blood contact portions such as the inner surfaces of the port cap members 3 and 4 or the surface of the urethane resin 12 are kept in a wet state, the hydrophilic polymer is crosslinked on the surface of the carrier by irradiation with radiation. By keeping the saccharide in the network structure, the retention rate of the saccharide on the surface of the carrier such as a module is increased.
In this hydrophilization treatment step, saccharides can be mainly adhered and held only on the surface of the carrier by the hydrophilizing agent, and only this surface can be selectively hydrophilized.

With such a blood purifier and its manufacturing method, a hollow fiber, which is a carrier for blood purification, is made into a module, and then a saccharide or a solution in which a saccharide and a hydrophilic polymer are mixed is brought into contact with the blood contact portion side. By drying in a wet state with these solutions, saccharides can be attached and subjected to a hydrophilic treatment.
As a result, it is possible to eliminate the need for the use of a polymer-based hydrophilizing agent that has been used in a large amount for hydrophilicity until now, or to reduce the amount used. It is possible to eliminate the worry of eluting from the carrier, moving to the patient's body and accumulating, and improving safety.

Further, by using trehalose which is a disaccharide as a hydrophilizing agent, an effect that is said to have a function of suppressing trehalose protein aggregation (β sheet formation) can be expected. That is, dialysis patients have an extremely high probability of developing dialysis amyloidosis due to β-sheet formation of a protein called β2-microglobulin in blood after prolonged dialysis, but trehalose is used as a hydrophilizing agent. It can be expected that the onset of such a pathological condition is delayed by setting it to be adhered and held on the surface of the body.
Furthermore, by using trehalose which is a disaccharide as a hydrophilizing agent, trehalose can be expected to have an effect of stabilizing SOD (superoxide dismutase: enzyme that scavenges active oxygen) activity. In other words, in dialysis treatment, there is a high possibility of exposure to active oxygen due to the share stress and light during treatment, and this causes cell damage, but trehalose acts as a hydrophilizing agent on the surface of the carrier. Since it is in an adhering and holding state, it can be expected to stabilize the SOD activity and reduce the adverse effects of active oxygen.

  In addition, since the saccharide used as the hydrophilizing agent has a hydroxyl group (OH group) in the molecular structure, it has an effect of inducing complement activity (C3a, C5a, etc.) in blood. In apheresis treatment, activation of these may be required, and an effect can be expected when this blood purifier is used as an apheresis device.

Next, the blood purifier 1 is filled with water (step S6).
This water filling process is a treatment for facilitating replacement with physiological saline when the blood purifier 1 is used for blood purification therapy, and purifies both the blood contact portion side and the dialysate contact portion side. The filling port 7 of the injection side blood port cap member 3, the discharge port 8 of the discharge side blood port cap member 4, the inlet port 5 and the discharge port of the casing 2 are filled with water so that the filled purified water does not leak. Cap 6.
The blood purifier thus filled with water is a so-called wet type.
Even in the case of a wet type blood purifier, during the manufacturing process, the blood purification carrier such as hollow fiber membranes and beads is once dried and then filled with water for activation (rewetting). Sometimes shipped.

  Moreover, it does not interfere with a water filling process, and it does not interfere even if it is a module of the specification which does not fill with water through a drying process (step S6 '). The module having a specification not filled with water is called a so-called dry type, and has an advantage that it is lightweight and does not freeze in a cold region. This dry type blood purifier is used after being activated (re-wetted) with a physiological saline solution or the like.

Next, a sterilization process is performed on the blood purifier 1 filled with the purified water (step S7).
In this sterilization process, γ-ray sterilization and steam sterilization can be used for the blood purifier 1. Furthermore, the module of the specification not filled with water may use ethylene oxide sterilization in addition to γ ray sterilization and steam sterilization.

  In the blood purification device manufacturing process described above, the assembled blood purification device 1 is subjected to a hydrophilic treatment through an aqueous solution of saccharides and an aqueous solution of saccharides and hydrophilic polymers as a hydrophilic agent. In addition, the spinning process and the modularization process may be the same as before, and the existing manufacturing equipment can be used effectively.

In the above description, the example in which the hydrophilic treatment is performed in a state where both the blood port cap members 3 and 4 are connected is described. However, the hydrophilic treatment of both the blood port cap members 3 and 4 is performed as necessary. Therefore, only the casing 2 (that is, the module) in which the middle yarn bundle 9 is loaded may be subjected to a hydrophilic treatment.
However, by performing the hydrophilization process with both blood port cap members 3 and 4 connected, all blood contact portions in the blood purifier 1 are hydrophilized collectively, so that the process is easy. Since the gaps between the respective parts are also made hydrophilic, the adhesion / remaining of blood components can be further reduced.

  Furthermore, in the above description, as a carrier for purification of a blood purifier that performs a hydrophilic treatment, the hollow fiber membrane is bundled into a module as an example, but as a carrier for a purifier, its shape is Is not limited to hollow fibers, and may be in the form of beads. As a hydrophilizing agent, a solution of saccharides or a mixed solution of saccharides and hydrophilic polymers can be used similarly. As a result, a blood purifier exhibiting the above effects can be obtained, and a blood purifier can be manufactured.

  A polymer stock solution was prepared from polyarylate resin (trade name; U polymer, manufactured by Unitika Ltd.), polyethersulfone resin (trade name; Sumika Excel, manufactured by Sumitomo Chemical Co., Ltd.), and N-methylpyrrolidone. The weight mixing ratio of the polyarylate resin and the polyethersulfone resin was 1: 1. Further, an N-methylpyrrolidone aqueous solution was used as a coagulating liquid and a core liquid. Then, the polymer stock solution was discharged into the coagulation liquid together with the core liquid using a double pipe spinneret to produce a hollow fiber membrane, and about 10,000 hollow fiber membranes were bundled to form a hollow fiber bundle.

  The hollow fiber bundle was dipped in an aqueous solution of polyvinylpyrrolidone (BASF, trade name: Rubytec K90PH) 0.5% and trehalose 0.5%, and then the hollow fiber bundle was dried by a microwave drying apparatus. Further, after the hollow fiber bundle is loaded in a cylindrical casing, the end portion is bonded (potted) with polyurethane resin to form a module, and caps having blood ports are put on both ends of the module to cover the membrane area 1 A 5 square meter blood purifier was made.

  The obtained blood purifier was subjected to a priming operation using a dialysis apparatus (manufactured by Nikkiso Co., Ltd., trade name: DBB-26), and urea clearance was measured according to the criteria of the Dialysis Medical Association. The results are shown in Table 1.

  Moreover, the blood purifier produced by the same method was washed with 1 liter of purified water. After the obtained blood purifier was heated at 70 ° C. for 3 hours, the filled liquid (blood contact part side liquid) was taken out and the concentration of polyvinylpyrrolidone was measured to obtain the polyvinylpyrrolidone concentration in the filling liquid. In addition, 500 ml of purified water was circulated at 70 ° C. at a flow rate of 200 ml / min for 4 hours with respect to the blood purifier from which the filling liquid had been extracted in the above test, and extracted to the purified water side by this circulation. The concentration of polyvinyl pyrrolidone was measured to obtain a polyvinyl pyrrolidone concentration in the extract. The results are shown in Table 1.

[Comparative Example 1]
A hollow fiber bundle produced by the same method as in Example 1 was immersed in a solution of 1.5% polyvinylpyrrolidone alone, and then dried and modularized by the same method as in Example 1 to produce a blood purifier.
Next, the urea clearance and the elution amount of polyvinylpyrrolidone were measured by the same method as in Example 1. The results are shown in Table 1.

[Comparative Example 2]
A hollow fiber bundle produced by the same method as in Example 1 was dried and modularized by the same method to produce a blood purifier. And the urea clearance and the elution amount of polyvinylpyrrolidone were measured by the same method as in Example 1. The results are shown in Table 1.

  As can be seen from Table 1, Example 1 immersed in a 0.5% aqueous solution of trehalose has the same urea clearance as that of Comparative Example 1 immersed in a solution of 1.5% polyvinylpyrrolidone alone, that is, urea removal. In addition to the necessary and sufficient capacity, the dissolution of polyvinylpyrrolidone is clearly small.

It is a flowchart which shows the outline of the manufacturing process of a blood purifier. It is the figure which showed the molecular weight fractionation characteristic of the hollow fiber membrane. It is explanatory drawing which made the blood purifier the cross section. It is the figure which showed the cut surface of the hollow fiber bundle in the edge part of a casing, (a) is the figure which showed the whole cut surface, (b) is the figure which expanded and showed a part.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Blood purifier 2 Casing 3 Inlet side blood port 4 Outlet side blood port 5 Dialysate inlet 6 Dialysate outlet 7 Blood inlet 8 Blood outlet 9 O-ring 10 Hollow fiber bundle 11 Opening of casing 12 Urethane resin 13 Hollow fiber membrane

Claims (5)

In the blood purifier to a hydrophobic polymer having an adsorption capacity with a carrier for purification such as a hollow fiber membrane or beads having a Material,
A blood purifier characterized in that trehalose and polyvinylpyrrolidone are adhered and held on the blood contact portion of the carrier for the purifier. The blood purifier according to claim 1 , wherein the amount of the trehalose adhered and held on the carrier is 10 mg to 10 g per square meter of the blood contact portion of the carrier . The blood purifier according to claim 1 or 2, wherein the hydrophobic polymer is made of a polyester resin and a polysulfone resin . Producing a bundle of hollow fiber membranes made of a hydrophobic polymer;
  Storing the bundle of hollow fiber membranes in a cylindrical casing, and sealing and sealing between the blood contact portion and the dialysate contact portion; and
  A step of bringing trehalose and polyvinylpyrrolidone into contact with the blood contact portion side of the module and then drying and attaching and holding,
  A method for producing a blood purifier comprising the steps of: The method for producing a blood purifier according to claim 4, further comprising a step of crosslinking the polyvinyl pyrrolidone by irradiation to retain the trehalose.

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