JP2008295868A - Method for producing blood purifier and blood purifier - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for cleaning oily materials loaded in hollow parts while leaving a pore size keeping agent for hollow fiber membranes such as glycerin or the like which avoids the destruction of the earth environment that is seen when using solvents such as chlorofluorocarbons or the like for cleaning oily materials such as liquid parafin loaded in hollow parts of hollow fiber membranes, avoids danger of ignition, dispenses with installation of explosion-proof equipment, and solves the problem of deterioration of a case for storing a hollow fiber membrane bundle due to the solvents. <P>SOLUTION: In a method for cleaning a hollow fiber membrane, a hollow fiber membrane bundle is loaded in a case of a blood purifier, both ends are fixed by a bonding resin, and gas whose temperature and humidity are adjusted to a temperature of ≥5°C and ≤40°C and to a relative humidity of ≥30% and ≤70% is supplied to the hollow parts of the hollow fiber membranes. By doing so, a hollow forming agent remaining in the hollow parts is removed. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a method for producing a blood purifier that efficiently removes a hollow forming agent at a low cost from a hollow fiber membrane used in a blood purifier or the like.

As blood purification membrane to complement reduced patient renal function renal function, the initial urea and has been used to remove low molecular substances such as creatinine, in recent molecular weight within such beta ₂ microglobulin A so-called hollow fiber membrane type high-performance blood purification membrane capable of efficiently removing proteins has been developed and its importance is increasing.

  Conventionally, when extruding a solution of a polymer such as cellulose, cellulose acetate, cellulose triacetate, polyacrylonitrile, polymethylmethacrylate, polymer and solvent and / or non-solvent from the outer annular portion of the double annular orifice, A hollow fiber membrane filled with an oily substance has been manufactured by simultaneously discharging oily substances such as liquid paraffin and isopropyl myristate from the inner tube of the double annular orifice. A plurality of hollow fiber membranes manufactured in this way are bundled and loaded into a blood purifier case made of plastic such as polystyrene resin, acrylic resin, polycarbonate resin, etc., and both ends of the hollow fiber membrane bundle are fixed with an adhesive. After that, a blood purifier has been manufactured by cutting a part of the bonded portion and opening the end portion of the hollow fiber membrane.

  The oily substance filled in the hollow fiber membrane was removed by passing fluorocarbon through the hollow portion of the hollow fiber membrane before or after inserting the hollow fiber membrane into a case such as a blood purifier. However, since chlorofluorocarbons destroy the ozone layer, they are moving to stop production mainly in developed countries, and switching to alternative cleaning methods is progressing. In this regard, cleaning with a fluorinated hydrocarbon compound, a fluorinated carbon compound, an organic solvent, or the like has been studied.

However, each has practical limitations and cannot necessarily be a perfect substitute. Fluorinated hydrocarbon compounds such as compounds represented by the structural formula C ₂ H ₃ Cl ₂ F (Patent Document 1) and compounds represented by the structural formula C ₃ HCl ₃ F are eroded by plastics such as acrylic resins and polycarbonate resins. (For example, the surface is rough, whitening due to partial dissolution, cracks, etc.), and the hollow forming agent remaining in the hollow portion of the hollow fiber membrane could not be washed away after the blood purifier was assembled. In the case of the compound represented by the structural formula C ₃ HCl ₅ F ₅ , the glycerin contained as the pore size retaining agent is partially dissolved, which causes a problem of reducing the membrane performance.
JP 07-138807 A

On the other hand, a fluorocarbon compound (Patent Document 2) basically has no ability to dissolve an oily substance, but because of its low surface tension, it penetrates between the film material and the oily substance and peels the oily substance from the film surface. Can be removed. However, since it physically peels, there is a disadvantage that the efficiency is poor and a large amount of the compound is required. Furthermore, it is necessary to consider the impact on global warming. Moreover, although an oily substance can be selectively dissolved and removed by using an aliphatic hydrocarbon such as hexane (Patent Document 3) or Nonane (Patent Document 4), an explosion-proof facility is essential because it has a flash point. Because it leads to increased work safety and cost, it cannot simply be replaced.
Japanese Patent Laid-Open No. 06-285160 Japanese Patent Laid-Open No. 06-285161 Japanese Patent Laid-Open No. 10-225627

  On the other hand, establishment of a safe, good workability, and inexpensive cleaning method that replaces the above-described cleaning method using a solvent is required.

Patent Document 5 discloses a non-coagulating liquid inside a hollow fiber membrane by blowing temperature-controlled humidity air at a temperature of 50 to 120 ° C. and / or a relative humidity of 20 to 100% toward one end of the hollow fiber membrane bundle. A method of removing is disclosed. This is an inexpensive cleaning method that can remove the hollow forming agent without using a cleaning liquid such as chlorofluorocarbon, and has a low environmental load. However, the hollow fiber membrane described in the document is intended for a hollow fiber membrane having a water permeability of 2.5 to 60 mL / m ² / hr / mmHg, a small pore diameter, and no pore filled with glycerin. .
JP 07-252721 A

In Patent Document 6, most of the core liquid is removed from the hollow fiber by centrifugation, compressed air extrusion, and natural dropping in combination, and then the hollow fiber is housed and bonded in the dialyzer and further remains in the hollow fiber in the dialyzer. A method of physically removing the core liquid to be removed with a pressurized gas and water is disclosed. According to this technique, since the core fluid removal operation before and after the production of the blood purifier is necessary, such an operation is very complicated, and the associated cost is hardly small.
Japanese Patent Laid-Open No. 08-164200

  The present invention does not change the membrane structure of the hollow fiber membrane, and there is no problem of a decrease in productivity due to poor filling of the adhesive resin when adhering to the end of the hollow fiber membrane at the time of hemodialyzer assembly. Remains and selectively removes the hollow forming agent (oily substance) present in the hollow part of the hollow fiber membrane, and flammability, environmental destruction, blood purifier manufacture without deteriorating the case containing the hollow fiber membrane bundle Provided is a method for removing a hollow forming agent from a hollow portion of a hollow fiber membrane, which solves various problems related to cost.

Corrected when claim is confirmed.
It has been found that these problems can be solved by the present invention. That is, the present invention
(1) After the hollow fiber membrane bundle is loaded into a blood purifier case and both ends are fixed with an adhesive resin, the temperature is adjusted to a temperature of 5 ° C. to 40 ° C. and the relative humidity is 30% to 70%. In the hollow portion of the hollow fiber membrane to remove the hollow forming agent remaining in the hollow portion.
(2) The method for producing a blood purifier is characterized in that the hollow forming agent is an oily substance.
(3) The method for producing a blood purifier is characterized in that the oily substance is liquid paraffin or isopropyl myristate.
(4) The method for producing a blood purifier is characterized in that the hollow fiber membrane contains a pore diameter retaining agent in the pores.
(5) The blood purifier manufacturing method is characterized in that the pore diameter maintaining agent is mainly glycerin or a glycerin derivative.
(6) Moreover, it is a manufacturing method of the blood purifier characterized by the adhesion rate of a pore diameter maintaining agent being 30 to 80% by weight.
(7) The method for producing a blood purifier is characterized in that the pressure when flowing a gas through the hollow portion of the hollow fiber membrane is 0.05 to 0.20 MPa.
(8) Moreover, it is a manufacturing method of the blood purifier characterized by the porosity of a hollow fiber membrane being 30 to 85%.
(9) A blood purifier produced by any one of the methods described above.
(10) The blood purifier is characterized in that the residual amount of the oily substance is 100 mg / (2.1 m ² module) or less.

  According to the method of the present invention, the oily substance filled in the hollow portion of the hollow fiber membrane can be removed while suppressing the falling off of the water-soluble pore diameter retaining agent such as glycerin impregnated in the hollow fiber membrane. That is, since the removal operation hardly causes the shrinkage of the pores caused by the removal of the pore diameter retaining agent, the performance of the hollow fiber membrane is hardly deteriorated. Further, in the present invention, since a chlorofluorinated hydrocarbon compound, a fluorinated carbon compound, an organic solvent, or the like is not used for washing and removing the oily substance, environmental destruction, risk of ignition, and a case for housing a hollow fiber membrane bundle are accommodated. There is no problem with solvent degradation. In addition, the present invention fills the end of the hollow fiber membrane bundle into a blood purifier case, and adheres the end with an adhesive resin, and then removes the oily substance in the hollow with a temperature-controlled humidity gas. The problem of poor filling of the end urethane resin does not occur. Furthermore, in the present invention, since no chlorofluorinated hydrocarbon compound, fluorinated carbon compound, organic solvent, or the like is used, it is not necessary to install an explosion-proof facility, which greatly reduces the cost of manufacturing a blood purifier.

  Hereinafter, the present invention will be described in detail.

  In the present invention, the method for producing the hollow fiber membrane is not particularly limited. For example, a spinning stock solution composed of a polymer, a solvent, and a non-solvent is discharged from the outer annular portion of the double tubular nozzle, and at the same time, the hollow forming agent is discharged from the inner tube. There is a dry and wet spinning method in which it is discharged and passed through the air gap portion and then immersed in a coagulating liquid. The obtained hollow fiber membrane is subsequently removed with an excess solvent and non-solvent in a water washing tank, and then impregnated with a pore diameter retaining agent in the pores of the hollow fiber membrane, dried and wound up. As the pore diameter retaining agent, glycerin, polyethylene glycol, polypropylene glycol or the like is used, and glycerin is particularly preferably used.

  In the present invention, the material of the hollow fiber membrane is not particularly limited as long as it can be spun using an oily substance as a hollow forming agent. Cellulose, cellulose acetate, cellulose triacetate, polyacrylonitrile, polymethyl methacrylate, polysulfone, polysulfone A polymer such as ether sulfone is preferably used. Of these, cellulose acetate polymers such as cellulose acetate and cellulose triacetate, and polysulfone polymers such as polysulfone and polyethersulfone are more preferably used. The polymer concentration in the spinning dope is preferably 15 to 50% by weight. The present invention is preferably applied to a hollow fiber membrane in which pores are filled with a pore size retainer, but is close to a homogeneous structure from the viewpoint of retaining the pore size retainer (preventing the removal of the pore size retainer from the pores). More preferably, it is a membrane. If the polymer concentration in the spinning dope is in the above range, the hollow fiber membrane can easily have a homogeneous structure.

  In the present invention, examples of the solvent for the polymer include N-methyl-2-pyrrolidone, dimethylacetamide, dimethylformamide, dimethyl sulfoxide, etc., and it is easy to control the coagulation and phase separation of the cellulose acetate polymer and the polysulfone polymer. From the viewpoints of work safety and disposal, N-methyl-2-pyrrolidone and dimethylacetamide are preferably used.

Further, as the non-solvent for the polymer, glycerin, ethylene glycol, triethylene glycol, polyethylene glycol, and the like are preferably used. From the viewpoint of compatibility with the solvent, washing removal property, and safety, triethylene glycol and polyethylene glycol are preferable. More preferred. Polyethylene glycol having a molecular weight of 200 or 400 is preferably used because it is liquid at room temperature and has excellent handleability.
Furthermore, additives such as an antioxidant and a micropore forming agent can be added to the spinning dope as necessary.
The solvent / non-solvent ratio in the spinning dope is preferably 97/3 to 40/60 because the stability of the spinning dope increases and a homogeneous membrane structure is easily obtained. 90 / 10-50 / 50 is more preferable, and 80 / 20-60 / 40 is more preferable.

  In the present invention, the hollow forming agent is not particularly limited, but a liquid that does not coagulate the spinning dope is preferable because the effects of the present invention are more effectively expressed. Specific examples of such a hollow forming agent include nonane, decane, undecane, dodecane, liquid paraffin, and isopropyl myristate. Liquid paraffin and isopropyl myristate are more preferable from the viewpoints of safety, availability, and nozzle temperature.

  The nozzle temperature when discharging the spinning dope and the hollow forming agent from the double tubular nozzle is preferably 100 to 185 ° C. Within such a temperature range, there is a relationship with the spinning solution viscosity and the hollow forming agent boiling point, but it is preferable because not only stable discharge is obtained but also the coagulation and phase separation of the spinning solution are easily controlled. 110-180 degreeC is more preferable, and 120-175 degreeC is further more preferable.

The spinning dope discharged from the nozzle is immersed in a coagulation bath through an air gap of 3 to 150 mm. If the air gap length is too short, the liquid surface and nozzle surface come into contact with each other when the liquid surface of the coagulation bath sways, causing thread breakage, or the nozzle temperature is not stable when the temperature of the coagulation bath is low. May occur. On the other hand, if the air gap length is too long, the spinning dope will be affected by gravity and the hollow fiber membrane dimensions will be easily spotted, or thread breakage may occur, which causes problems in terms of quality and operation. May occur. Therefore, the air gap length is more preferably 3 to 100 mm, and further preferably 3 to 50 mm.
Since the temperature and humidity of the air gap portion have a considerable influence on the film structure, it is preferable to take appropriate adjustment means. However, in the present invention, the nozzle temperature may be relatively high, and the air gap portion is shut off from the outside air. It is possible to ensure sufficient spinning, hollow fiber membrane performance and quality stability even when surrounded by the members.

  The spinning dope that has passed through the air gap is immersed in a coagulation bath to cause coagulation and phase separation to proceed. Here, as the coagulation liquid, it is preferable to use the solvent used for the preparation of the film-forming solution and a mixed liquid of a non-solvent and water. Since the structure and characteristics of the hollow fiber membrane obtained by the coagulation liquid composition change, it is necessary to determine the mixing ratio of the solvent, non-solvent, and water by trial and error according to the target membrane structure and membrane characteristics. In the present invention, the solvent and non-solvent used for the preparation of the coagulation liquid are preferably the same as those used for the preparation of the film-forming solution, and in addition, the film-forming is performed in order to suppress the change in composition over time during film-forming. It is preferable to use the same solvent and non-solvent ratio in the solution.

  The hollow fiber membrane of the present invention has a more preferable homogeneous structure. However, in addition to the polymer concentration in the spinning dope described above, it is preferable that the hollow forming agent type, the air gap length, the coagulation bath conditions, etc. be within the above ranges. It has a considerable impact on structure determination.

  The hollow fiber membrane withdrawn from the coagulation bath is subsequently guided to a washing step to remove the solvent, non-solvent and the like used for the hollow fiber membrane formation. The structure of the cleaning apparatus and the cleaning liquid to be used are not particularly limited, but the cleaning liquid may be any solvent and non-solvent compatible, and water, alcohol, etc. can be used. More preferably it is used. More preferably, from the viewpoint of preventing contamination of the hollow fiber membrane and washing efficiency, water obtained by further performing reverse osmosis membrane treatment is used.

  The hollow fiber membrane after completion of the cleaning is subsequently led to a process for impregnating the pore diameter retainer into the hollow fiber membrane pores. In the present invention, it is preferable to use glycerin or a glycerin derivative as the pore diameter retaining agent. The glycerins are highly safe substances used for pharmaceuticals and cosmetics, but have a high viscosity at room temperature. Therefore, it is not easy to impregnate the hollow fiber membrane pores with the stock solution. Accordingly, a mixture of glycerin and water is heated to 100 ° C. or lower and then brought into contact with the hollow fiber membrane to impregnate the pores. The glycerin concentration and temperature in the solution need to be appropriately set depending on the size and number of pores of the hollow fiber membrane, and the distribution state, but if the hollow fiber membrane of the present invention is in the UFR range, 15 to 90 wt. % Aqueous glycerin solution is heated to 30 to 80 ° C., and then the hollow fiber membrane is immersed and impregnated in the pores. If the glycerin concentration is too low, the impregnation property into the pores of the hollow fiber membrane is enhanced, but the pores contract by the amount of water evaporated by drying, so that the desired membrane characteristics may not be obtained. Accordingly, the glycerin concentration is more preferably 18% by weight or more, and further preferably 21% by weight or more. On the other hand, if the glycerin concentration is too high, the effect of maintaining the pore diameter is increased, but the viscosity is increased, so that the impregnation property into the pores may be lowered. In order to reduce the viscosity of the aqueous glycerin solution, the temperature may be increased. However, the glycerin itself may be thermally oxidized or the hollow fiber membrane may be damaged. Therefore, the glycerin concentration is more preferably 87% by weight or less, and still more preferably 84% by weight or less.

  The hollow fiber membrane impregnated with the glycerin aqueous solution is then dried in a drying step. The drying temperature is preferably 40 to 120 ° C. Here, the purpose of drying the hollow fiber membrane is not only to reduce the weight of the hollow fiber membrane by evaporating the water contained in the hollow fiber membrane, but also to ensure the assembly of the blood purifier (the potting agent remains) Prevents poor adhesion due to reaction with water), prevents glycerin from falling off (decreases fluidity of glycerin by evaporating excess water), immobilizes membrane structure (due to temperature changes during storage and transportation) And the like). If the drying temperature is too low, water cannot be instantly evaporated and glycerin may fall off. Therefore, the drying temperature is more preferably 45 ° C. or higher, and further preferably 50 ° C. or higher. Also, if the drying temperature is too high, glycerin may undergo thermal oxidation. Therefore, the drying temperature is more preferably 115 ° C. or less, and further preferably 110 ° C. or less.

The hollow fiber membrane thus obtained preferably has an inner diameter of 150 to 300 μm, a film thickness of 10 to 50 μm, and a porosity of 30 to 85%. If the inner diameter is too small, there is a possibility that when the gas for extruding the hollow forming agent is introduced into the blood purifier, the pressure loss is large and the hollow forming agent cannot be removed efficiently. Conversely, if the inner diameter is too large, the linear velocity of the gas will not increase, and the hollow forming agent may not be removed efficiently. On the other hand, there is little problem because the porosity is too low, but if the porosity is too high, the hollow fiber membrane may crack or burst without being able to withstand the pressure of the gas. Therefore, it is the porosity of 40 to 85% and 50 to 85% that the effects of the present invention are remarkably exhibited. As the performance of the hollow fiber membrane having the porosity, the water permeability is 70 to 400 ml / m ² / hr / mmHg.

  It is preferable to apply the method of the present invention to a hollow fiber membrane having a relatively high pore diameter retention agent adhesion rate because the effect is remarkably exhibited. Specifically, the pore diameter retention agent adhesion rate is preferably 30 to 80% by weight. The effect appears more remarkably in the range of 45 to 80% by weight, and further in the range of 60 to 80% by weight. When the pore diameter retention agent adhesion rate is relatively low, the gas extrusion conditions for removing the hollow forming agent do not require much consideration.

  The obtained hollow fiber membrane is bundled in a bundle of about 5,000 to 20,000, accommodated in a case such as a blood purifier, the end is fixed with an adhesive resin, and then a part of the resin is cut. The hollow part is opened to make a blood purifier. If the hollow portion is filled with an oily substance, it cannot be used as a blood purifier. Therefore, it is necessary to remove the oily substance in the hollow part before or after the blood purifier is manufactured. In the present invention, a method of removing the oily substance after manufacturing the blood purifier is adopted from the viewpoint of oily substance removal and work efficiency.

  As a method for removing the oily substance, there are a method of removing the oily substance using a liquid such as a hydrocarbon solvent or a surfactant aqueous solution, a method of using compressed air, centrifugal force, and natural fall, but each has advantages and disadvantages. In the present invention, a method of extruding an oily substance using a gas under specific humidity, temperature and pressure conditions is employed.

  In the present invention, as the type of gas used to remove the oily substance filled in the hollow portion of the hollow fiber membrane, air and inert gas such as nitrogen, argon, helium, etc. are used. Air is preferably used.

  In this invention, it is preferable that the temperature of the gas at the time of extruding an oily substance from a hollow part of a hollow fiber membrane shall be 5 degreeC or more and 40 degrees C or less. If the temperature of the gas is too low, moisture in the supplied gas may condense in the pipe and clog the pipe. Therefore, the temperature of the gas is more preferably 10 ° C or higher, and further preferably 15 ° C or higher. On the other hand, if the gas temperature is too high, the viscosity of the pore diameter holding agent is lowered and may fall out of the pores, so the gas temperature is more preferably 38 ° C. or less, and even more preferably 35 ° C. or less.

  In the present invention, the relative humidity of the gas used for extruding the oily substance from the hollow portion of the hollow fiber membrane is preferably 30% or more and 70% or less. It is preferable that the moisture content of the hollow fiber membrane having a pore diameter retaining agent such as glycerin, polyethylene glycol, or polypropylene glycol is maintained within a range of 5% or more and 20% or less in the blood purifier assembly process. When the hollow fiber membrane is exposed to a low-humidity atmosphere, the drying proceeds, shrinks, the pore diameter and the porosity decrease, and the hollow fiber membrane performance may deteriorate. Therefore, the moisture content of the hollow fiber membrane is preferably 5% or more. Conversely, when exposed to a high-humidity atmosphere, the pore diameter retainer of the hollow fiber membrane may absorb moisture, causing the viscosity of the pore diameter retainer to decrease and fall out of the pores. Further, the dropped glycerin may block the hollow portion of the hollow fiber membrane and cause blood impermeability during clinical use. Therefore, the moisture content of the hollow fiber membrane is preferably 20% or less. When the oily substance in the hollow portion of the hollow fiber membrane is removed using gas, if the humidity of the gas is too low, the pore diameter holding agent filled in the hollow fiber membrane pores is dehydrated, leading to the above problems. In addition, if the humidity of the gas is too high, the pore diameter retaining agent absorbs moisture, leading to the occurrence of the above problem. Therefore, the relative humidity of the gas used is more preferably 35% or more and 65% or less.

  In the present invention, the pressure for introducing the gas used to remove the oily substance filled in the hollow portion of the hollow fiber membrane into the hollow portion of the hollow fiber membrane is preferably 0.05 to 0.20 MPa. If the pressure is too low, the oily substance present in the hollow portion may not be sufficiently removed or it may take a long time to remove, so the gas pressure is more preferably 0.06 MPa or more, and 0.07 MPa. The above is more preferable. On the other hand, if the pressure is too high, the hollow fiber membrane may be damaged, or micro scratches generated in the spinning process and blood purifier assembly process may be enlarged. Therefore, the gas pressure is preferably 0.19 MPa or less. 0.18 MPa or less is more preferable.

  In the present invention, the method for adjusting the temperature-controlled humidity gas supplied to the hollow portion of the hollow fiber membrane is not particularly limited. A gas whose temperature and humidity are adjusted in advance may be supplied by a compressor or the like, or a gas adjusted by providing a humidification tank in the middle of an air supply line may be used.

  In the present invention, when removing the oily substance in the hollow part of the hollow fiber membrane, a method of introducing a temperature-controlled humidity gas after filling the hollow fiber membrane bundle into the blood purifier case and fixing both ends with urethane resin Is preferably adopted. If both ends of the hollow fiber membrane bundle are fixed with a urethane resin and then a temperature-controlled humidity gas is allowed to flow into the hollow part, the hollow forming agent can be efficiently removed, and hydrophilic such as glycerin is contained in the hollow fiber membrane pores. Even with so-called High Flux hollow fiber membranes, which are filled with a porous pore size retainer, it is possible to efficiently remove the hollow forming agent without causing the pore size retainer to drop off and without causing poor urethane resin adhesion. It becomes. By taking such consideration into consideration, it is possible to avoid a decrease in the performance and quality of the hollow fiber membrane.

(Measurement of water permeability)
The blood outlet circuit (outlet side of the pressure measurement point) of the dialyzer is stopped by a forceps and subjected to total filtration. Purified water kept at 37 ° C is put into a pressurized tank, and the pressure is controlled by a regulator. The pure water is sent to a dialyzer kept warm in a 37 ° C constant temperature bath, and the amount of filtrate flowing out from the dialysate side is measured with a graduated cylinder. To do. The transmembrane pressure difference (TMP) is TMP = (Pi + Po) / 2
And Here, Pi is the dialyzer inlet side pressure, and Po is the dialyzer outlet side pressure. The TMP is changed at four points, the filtration flow rate is measured, and the water permeability (mL / hr / mmHg) is calculated from the slope of the relationship. At this time, the correlation coefficient between TMP and the filtration flow rate must be 0.999 or more. In order to reduce the pressure loss error due to the circuit, TMP is measured in the range of 100 mmHg or less. The water permeability of the hollow fiber membrane is calculated from the membrane area and the water permeability of the dialyzer.
UFR (H) = UFR (D) / A
Here, UFR (H) is the water permeability of the hollow fiber membrane (ml / m ² / hr / mmHg), UFR (D) is the water permeability of the dialyzer (ml / hr / mmHg), and A is the membrane area of the dialyzer ( m ² ).

(Measurement method of moisture content)
The moisture content of the hollow fiber membrane in the present invention is calculated by the following formula.
Moisture content (wt%) = 100 × (Ww−Wd) / Ww
Here, Ww is the weight (g) of the hollow fiber membrane, and Wd is the weight (g) of the hollow fiber membrane after being dried for 2 hours in a dry heat oven at 120 ° C. (after absolutely dry). Here, by setting Ww within the range of 1 to 2 g, it can be in an absolutely dry state (no more weight change) after 2 hours.

(Measurement method of glycerin adhesion rate)
The adhesion rate of the pore diameter retaining agent to the hollow fiber membrane was measured as follows.
The obtained hollow fiber membrane is made into a bundle of about 10,000 pieces, cut into a length of about 20 cm, sufficiently removed the liquid paraffin in the hollow portion by centrifugal drainage, completely dried, and the weight W is measured. Thereafter, the hollow fiber membrane bundle is immersed in a considerable amount of water heated to 40 ° C., thoroughly washed, dried in a 120 ° C. dry heat oven for 2 hours, and the weight P is measured. Next, the adhesion rate G (wt%) of the pore diameter retaining agent to the hollow fiber membrane was calculated by the following formula.
G (wt%) = (WP) / W × 100

Example 1
After mixing 22% by weight of cellulose triacetate (Daicel Chemical), 62% by weight of N-methyl-2-pyrrolidone (Mitsubishi Chemical), and 16% by weight of triethylene glycol (Mitsui Chemicals), the mixture was heated to dissolve and spun. The stock solution was used. This was extruded from the outer annular portion of a double tubular nozzle heated to 150 ° C., and at the same time, liquid paraffin was discharged from the inner tube. A hollow fiber membrane was formed through a 50 mm air gap and led to a coagulation bath at 25 ° C. consisting of 13% by weight of N-methyl-2-pyrrolidone, 2% by weight of triethylene glycol and 85% by weight of water. Subsequently, after passing the hollow fiber membrane through a water washing tank at 45 ° C. to remove excess solvent and non-solvent, the hollow fiber membrane is led to a glycerin bath and filled with a glycerin aqueous solution in the pores of the hollow fiber membrane, followed by a drying process at 70 ° C. Let dry. The obtained dry hollow fiber membrane had an inner diameter of 200 μm, a film thickness of 15 μm, and a porosity of 63%. 8800 hollow fiber membranes were bundled and loaded into a cylindrical case made of polycarbonate resin, and both ends were fixed with urethane resin. A portion of the resin was cut to open the hollow portion, and a blood purifier having a membrane area of 1.1 m ^{2 based} on the hollow fiber membrane inner diameter reference was obtained. The liquid paraffin remaining in the hollow part of the hollow fiber membrane is partially removed by natural fall beforehand, and then the air adjusted to a temperature of 20 ° C. and a relative humidity of 32% is 0.18 MPa for 15 minutes from the end of the blood purifier. It flowed into the hollow part.
Various evaluation was performed using the blood purifier from which the hollow forming agent was removed. The results are summarized in Table 1.

(Comparative Example 1)
The blood purifier obtained in the same manner as in Example 1 was flowed with air at a temperature of 25 ° C. and a relative humidity of 3% at 0.18 MPa for 15 minutes. The amount of liquid paraffin remaining was 95 mg / 2.1 m ² module. However, the water permeability of the assembled blood purifier was 50 ml / m ² / hr / mmHg, which was lower than that of the blood purifier of Example 1. Since the relative humidity of the extruded air is low, it seems that the hollow fiber membrane has been dried and the pores have contracted.

(Example 2)
A blood purifier was obtained in the same manner as in Example 1, and air having a temperature of 35 ° C. and a relative humidity of 67% was allowed to flow from the end of the blood purifier at 0.18 MPa for 15 minutes. The amount of residual liquid paraffin was 70 mg / 2.1 m ² or less, and the assembled blood purifier had a water permeability of 80 ml / m ² / hr / mmHg.

(Comparative Example 2)
A blood purifier obtained in the same manner as in Example 1 above was ventilated with air at a temperature of 25 ° C. and a relative humidity of 40% from the end of the blood purifier at 0.04 MPa for 15 minutes. The amount of residual liquid paraffin was as high as 466 mg / 2.1 m ² module and was insufficiently removed. The water permeability of the assembled blood purifier was 72 ml / m ² / hr / mmHg.

(Comparative Example 3)
Blood having a temperature of 25 ° C. and a relative humidity of 80% was allowed to flow through the blood purifier obtained in the same manner as in Example 1 from the end of the blood purifier at 0.18 MPa for 15 minutes. The amount of residual liquid paraffin was as low as 69 mg / 2.1 m ² module, but the water permeability of the blood purifier was as low as 48 ml / m ² / hr / mmHg. When the amount of the pore size retaining agent was measured, it was lower than that in Example 1. It was thought that the cause was that the glycerin absorbed moisture, the viscosity decreased, and dropped out of the pores because the relative humidity was high.

(Comparative Example 4)
Blood having a temperature of 25 ° C. and a relative humidity of 80% was allowed to flow from the end of the blood purifier at 0.5 MPa for 15 minutes to the blood purifier obtained in the same manner as in Example 1. The amount of liquid paraffin remaining was 46 mg / 2.1 m ² module, but the module leak test pass rate was as low as 75%. Probably because the pressure of the extrusion air was too high, glycerin in the pores of the hollow fiber membrane dropped out, and it seems that leak occurred.

(Example 3)
After mixing 22% by weight of cellulose triacetate (Daicel Chemical), 62% by weight of N-methyl-2-pyrrolidone (Mitsubishi Chemical), and 16% by weight of triethylene glycol (Mitsui Chemicals), the mixture was heated to dissolve and spun. The stock solution was used. This was extruded from the outer annular portion of a double tubular nozzle heated to 150 ° C., and at the same time, liquid paraffin was discharged from the inner tube. A hollow fiber membrane was formed through a 50 mm air gap and led to a coagulation bath at 25 ° C. consisting of 13% by weight of N-methyl-2-pyrrolidone, 2% by weight of triethylene glycol and 85% by weight of water. Subsequently, after passing the hollow fiber membrane through a water washing tank at 45 ° C. to remove excess solvent and non-solvent, the hollow fiber membrane is led to a glycerin bath and filled with a glycerin aqueous solution in the pores of the hollow fiber membrane, followed by a drying process at 70 ° C. Let dry. The obtained dry hollow fiber membrane had an inner diameter of 200 μm, a film thickness of 15 μm, and a porosity of 63%.
8800 hollow fiber membranes were bundled and loaded into a cylindrical case made of polycarbonate resin, and both ends were fixed with urethane resin. A portion of the resin was cut to open the hollow portion, and a blood purifier having a membrane area of 1.1 m ^{2 based} on the hollow fiber membrane inner diameter reference was obtained. The liquid paraffin remaining in the hollow part of the hollow fiber membrane is partly removed by natural fall beforehand, and then the air adjusted to a temperature of 20 ° C. and a relative humidity of 32% is 0.07 MPa for 15 minutes from the end of the blood purifier. It flowed into the hollow part.

Example 4
After mixing 18% by weight of cellulose triacetate (Daicel Chemical), 57.4% by weight of N-methyl-2-pyrrolidone (Mitsubishi Chemical) and 24.6% by weight of triethylene glycol (Mitsui Chemicals), the mixture was heated. And dissolved into a spinning dope. This was extruded from the outer annular portion of a double tubular nozzle heated to 150 ° C., and at the same time, liquid paraffin was discharged from the inner tube. A hollow fiber membrane was formed through a 45 mm air gap portion and led to a 35 ° C. coagulation bath consisting of 10.5 wt% N-methyl-2-pyrrolidone, 4.5 wt% triethylene glycol and 85 wt% water. Subsequently, after passing the hollow fiber membrane through a 50 ° C. water-washing tank to remove excess solvent and non-solvent, the hollow fiber membrane is led to a glycerin bath and filled with a glycerin aqueous solution in the pores of the hollow fiber membrane, followed by a drying process at 80 ° C. Let dry. The obtained dry hollow fiber membrane had an inner diameter of 200 μm, a film thickness of 17 μm, and a porosity of 78%.
8800 hollow fiber membranes were bundled and loaded into a cylindrical case made of polycarbonate resin, and both ends were fixed with urethane resin. A portion of the resin was cut to open the hollow portion, and a blood purifier having a membrane area of 1.1 m ^{2 based} on the hollow fiber membrane inner diameter reference was obtained. The liquid paraffin remaining in the hollow portion of the hollow fiber membrane is partly removed by natural fall in advance, and then the air adjusted to a temperature of 8 ° C. and a relative humidity of 67% is 0.18 MPa for 15 minutes from the end of the blood purifier. It flowed into the hollow part.

(Example 5)
Polyethersulfone (Sumitomo Chemtex 4800P) and BASF PVP (K-90) in a mixed solution of N-methyl-2-pyrrolidone (NMP) and triethylene glycol (TEG) (weight ratio 8: 2) They were mixed to 25 wt% and 3.5 wt%, respectively, and stirred at 150 ° C. to dissolve and make uniform solutions. This solution was degassed under reduced pressure, and then filtered through a sintered filter having a pore size of 15 μm to remove impurities, and a spinning stock solution was kept at 120 ° C. This spinning stock solution was discharged from the outer annular portion of a double annular nozzle heated to 120 ° C., and at the same time, liquid paraffin was discharged from the inner tube as a hollow forming agent. The discharged spinning solution was dropped into a 27 ° C. coagulation bath through a 210 mm air gap and coagulated. As the coagulation bath, a 15 wt% NMP aqueous solution was used. A hollow fiber membrane was formed by stretching 70% in a coagulation bath. The hollow fiber membrane pulled up from the coagulation bath was led to a water washing bath composed of 45 ° C. RO water to remove excess PVP and solvent. After passing through a 30% by weight glycerin aqueous solution bath, the pores were impregnated with glycerin, and then led into a hot air dryer at 60 ° C. for drying treatment. The dried hollow fiber membrane was wound around a bobbin with a winder at a speed of 75 m / min. The resulting hollow fiber membrane had an inner diameter of 200 μm, a film thickness of 16 μm, and a moisture content of 2.1% by weight.
8800 hollow fiber membranes were bundled and loaded into a cylindrical case made of polycarbonate resin, and both ends were fixed with urethane resin. A portion of the resin was cut to open the hollow portion, and a blood purifier having a membrane area of 1.1 m ^{2 based} on the hollow fiber membrane inner diameter reference was obtained. The liquid paraffin remaining in the hollow portion of the hollow fiber membrane is partially removed by natural fall in advance, and then the air adjusted to a temperature of 8 ° C. and a relative humidity of 67% is maintained at 0.18 MPa for 20 minutes from the end of the blood purifier. It flowed into the hollow part.

(Reference example)
A blood purifier was produced using a hollow fiber membrane obtained by the same method as in Example 1. From the end of the resulting blood purifier, n-hexane was flowed at a flow rate of 100 ml / min to remove the hollow forming agent. Various evaluations were made using this blood purifier and used as a comparative control. n-Hexane dissolves liquid paraffin but does not dissolve glycerin and does not deteriorate the hollow fiber membrane.

  As is clear from the results of the examples with respect to the reference examples, by using the blood purifier manufacturing method of the present invention, a cheap and safe blood purifier can be manufactured without causing a decrease in performance or quality deterioration of the blood purifier. I knew it was possible.

In the method for washing a hollow fiber membrane of the present invention, the lipophilic liquid present in the hollow part of the hollow fiber membrane is selectively removed to leave the glycerin as the pore diameter retaining agent, so that the permeation performance is not lowered by washing. In addition, since no solvent such as Freon is used, there is no adverse effect on the global environment. In addition, it is not necessary to install explosion-proof equipment, and a hemodialyzer can be manufactured economically because no solvent is required for cleaning. Therefore, it is important to contribute to the industry.

Claims (10)

  A hollow fiber membrane bundle is loaded into a blood purifier case, and both ends are fixed with an adhesive resin, and then a gas whose temperature is adjusted to a temperature of 5 to 40 ° C. and a relative humidity of 30 to 70% is hollow fiber. A method for producing a blood purifier, wherein the hollow forming agent remaining in the hollow portion is removed by flowing through the hollow portion of the membrane.   The method for producing a blood purifier according to claim 1, wherein the hollow forming agent is an oily substance.   3. The method for producing a blood purifier according to claim 1, wherein the oily substance is liquid paraffin or isopropyl myristate.   The method for producing a blood purifier according to any one of claims 1 to 3, wherein the hollow fiber membrane contains a pore diameter retaining agent in the pores.   The method for producing a blood purifier according to claim 4, wherein the pore diameter maintaining agent is mainly glycerin or a glycerin derivative.   6. The method for producing a blood purifier according to claim 4 or 5, wherein the adhesion rate of the pore diameter retaining agent is 30 to 80% by weight.   The method for producing a blood purifier according to any one of claims 1 to 6, wherein the pressure when the gas flows through the hollow portion of the hollow fiber membrane is 0.05 to 0.20 MPa.   The method for producing a blood purifier according to any one of claims 1 to 7, wherein the hollow fiber membrane has a porosity of 30 to 85%.   A blood purifier produced by the method according to claim 1. The blood purifier according to claim 9, wherein the residual amount of the oily substance is 100 mg / (2.1 m ² module) or less.