JPH10174850A - Treatment of hollow-fiber membrane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To reduce the shrinkage of a hollow-fiber membrane when heated by forming the hollow-fiber membrane by spinning, applying underwater constant-length wet heat treatment to the membrane, then removing the remaining solvent and drying the membrane under the conditions shown by specified inequalities. SOLUTION: When a hydrophobic membrane or the one made hydrophilic for treating body fluids is produced, the membrane is formed by wet or dry-wet solidification, and then underwater constant-length wet heat treatment and further constant-length wet heat treatment are applied under the conditions shown by inequalities I, II and III, where RH is the relative humidity (%) of the treating atmospher. T is the dry heat treating temp. ( deg.C), Tg is the glass- transition temp. ( deg.C) of the membrane, and (t) is the dry heat treating time (min). The under water constant-length wet heat treatment and constant-length wet heat treatment are perfoemed at 80-90 deg.C for >=2min. The material of the membrane is not specially limited, a high molecular compd. used in the medical field can be used, and a material consisting essentially of polysulfone, for example, is preferably used. Further, the hollow-fiber membrane contg. a hydrophilic polymer is preferably used.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for treating a hollow fiber membrane. More specifically, the present invention relates to a method for treating a hollow fiber membrane having a small shrinkage rate during heating, in which the hollow fiber membrane at the time of membrane formation is treated under specific conditions of wet heat treatment and dry heat treatment.

[0002]

2. Description of the Related Art In recent years, with the widespread development of membrane-type artificial organs, artificial kidneys, plasma separation, blood filtration such as blood filtration, etc.
Artificial organs using various membranes are widely used in the field of treatment such as ascites treatment, and have a great effect in terms of prolonging life and treatment. In particular, artificial organs using hollow fiber membranes have become the mainstream of artificial organs because of their compactness, low blood filling, and easy operation when used. These artificial organs need to be sterilized, and are subjected to ethylene oxide gas (EOG) sterilization, high-pressure steam sterilization, sterilization by γ-ray irradiation, and the like.

[0003] Among these sterilization methods, EOG sterilization has been widely used until now, but some cases considered to be caused by residual EOG have been recognized. Gamma-ray sterilization was limited at first due to concerns about denaturation of the material due to irradiation, but has been widely used as confirmation has progressed. However, long-term safety confirmation is necessary for each material used, and careful consideration is required for adoption.

[0004] High-pressure steam sterilization is a sterilization method that has been used in the medical field for a long time, and there is no problem in terms of safety. However, if sterilization is performed at 121 ° C for 20 minutes in a wet state, hollow fibers are not removed. In some cases, the film shrinks, causing troubles such as generation of a film defect and breakage of a bonded portion. Therefore, in order to avoid these problems, Japanese Patent Publication No. 3-62431 proposes a method in which the film is previously treated in a high-temperature and high-humidity atmosphere to cause the film to shrink by 2 to 6% in advance.

[0005]

However, according to this method, a large shrinkage of 2 to 6% occurs in the film, so that there is a problem that the physical properties and the permeability of the film are changed. In addition, a special heat treatment device is required for the treatment under high-temperature and high-humidity conditions, which is not always a satisfactory method in terms of workability and production cost. Therefore, an object of the present invention is to provide a method for treating a hollow fiber membrane that shrinks less when heated.

[0006]

The inventors of the present invention have investigated the causes of defects in the membrane and damage to the bonded portion that occur during high-pressure steam sterilization, and found that the hollow fiber membrane shrinks during sterilization. It was found that these problems did not occur if the content was 1% or less, more preferably 0.6% or less. As a result of intensive studies on a method of treating a hollow fiber membrane satisfying these conditions, it has been found that the object can be achieved by treatment in a high-temperature, low-humidity atmosphere completely different from the prior art, and the present invention has been completed. That is, the present invention, after spinning the hollow fiber membrane and performing a constant-humidity heat treatment in water, washing and removing the remaining solvent, further performing a constant-humidity heat treatment, and drying.
A method of treating a hollow fiber membrane, wherein the treatment is performed under the conditions (I) to (III). RH ≦ 10% (I) Tg−60 ° C. ≦ T ≦ Tg−20 ° C. (II) 10 ≦ t ≦ 90 (III) where RH: Relative humidity of processing atmosphere (% RH) T: Dry heat treatment temperature (° C.) ) Tg: Glass transition temperature of hollow fiber membrane (° C) t: Dry heat treatment time (min)

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention relates to a method for producing a hydrophobic or hydrophilized hydrophobic membrane for treating body fluids, which comprises forming the membrane by wet or dry-wet coagulation, and then performing a constant-temperature, constant-humidity heat treatment in water under specific conditions. And further characterized by performing a constant-length wet heat treatment. If the temperature of the underwater constant-humidity heat treatment is too high, the water permeability tends to decrease, and it is disadvantageous in terms of energy, and if it is too low, the effect of the present invention is small. It is preferable to carry out for more than one minute.

Next, after the solvent remaining in the hollow fiber membrane is washed and removed, the film is further subjected to a constant-length wet heat treatment in an aqueous solution of a plasticizer such as glycerin at the same temperature, dried, and dried under a predetermined condition. I do. In this case, the constant-length wet heat treatment is preferably performed at 80 to 90 ° C. for 2 minutes or more for the same reason as described above.

When the dry heat treatment is carried out at a temperature higher than the glass transition temperature (Tg) of the manufactured hollow fiber membrane, deformation of the membrane,
It is necessary to carry out the process at a temperature lower than Tg because the properties and permeation performance are greatly reduced and a film having excellent performance cannot be obtained. In the present invention, Tg-20 ° C or lower, and Tg-
Requires a temperature of 60 ° C. or higher.

[0010] The relative humidity (RH) during the heat treatment is also an important factor. If the humidity is high, the heat treatment effect more than expected occurs, and the film shrinks during the processing,
The transmission performance may decrease. In a completely dry state where there is almost no humidity, under the heat treatment conditions of Tg-20 ° C. to Tg-60 ° C., it is difficult to obtain the required heat treatment effect, and the heat treatment temperature is further increased. Even a slight change in T exceeds Tg, causing deformation of the film, deterioration of physical properties, permeation performance, and the like. In the present invention, the operation is performed at a relative humidity of 20% or less.

The dry heat treatment conditions (I) and (I)
I) and (III) are shown below. In the formula, RH is the relative humidity of the processing atmosphere (%), T is the dry heat treatment temperature (° C.), Tg
Is the glass transition temperature (° C.) of the hollow fiber membrane, and t is the dry heat treatment time (minutes). RH ≦ 10% (I) Tg−60 ° C. ≦ T ≦ Tg−20 ° C. (II) 10 ≦ t ≦ 90 (III)

The material of the hollow fiber membrane used in the present invention is not particularly limited. For example, polysulfone, polyamide,
High molecular compounds used in the medical field, such as polyacrylonitrile, polymethyl methacrylate, cellulose acetate and derivatives thereof can be used.

[0013] The hollow fiber membrane used in the present invention is prepared, for example, by using a membrane-forming stock solution to which a common solvent for the polymer for the membrane / pore-forming agent and / or hydrophilic polymer / a non-solvent is added if necessary. It is manufactured by extruding into the air simultaneously with the coagulating liquid in the core from the annular orifice, and then introducing into the coagulating liquid.

Next, the obtained hollow fiber membrane is led to a washing step, and after removing most of the common solvent in the membrane, heat treatment is preferably performed at a constant length in water, preferably at 80 to 98 ° C., followed by further washing. After completely removing the remaining solvent, heat fixation is carried out by heat treatment in an aqueous solution of a plasticizer such as glycerin, ethylene glycol, PEG or the like, preferably at a constant length of 80 to 90 ° C. Then, after performing normal bundle molding, such as frame winding, it is dried.

Using the membrane bundle thus heat-treated, a dialysis module,
Alternatively, a membrane blood processor such as a module for plasma separation is assembled. To sterilize the assembled module, wash it, fill the module with water or saline, etc.
Seal the module opening and perform high-pressure steam sterilization. After completion of the sterilization operation, the product is cooled to obtain a product, a membrane-type blood processor.

[0016]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below based on embodiments. The examples show typical results of the present invention, and the present invention is not limited to these examples. For the water permeability, a module with an effective length of 15 cm was prepared, a water pressure of 1 kg / cm ² was applied from the inside of the membrane with pure water at 25 ° C., and the amount of pure water permeating outside was measured. Is a value obtained by calculating the amount of water permeation.

The fractionated particle size is 0.1 kg by weight of an aqueous dispersion of monodisperse polystyrene particles, and is used at 25 ° C. and 0.5 kg / c.
Filtration was performed at a pressure of m ² , and the particle size was determined to be 90% or more, and the molecular weight cut off was performed under the same conditions using a solution in which 0.05% by weight of a protein was dissolved in a phosphate buffer.
Shown by the molecular weight of the protein that blocks 90% or more. The Tg of the film was measured by a differential thermal analyzer (DSC). The analysis of the film composition was measured by a nuclear magnetic resonance spectrometer (NMR) and ESCA.

Production Example 1 Polysulfone (UDEL P-1700, manufactured by Amoko)
20% by weight, 36% by weight of polyethylene glycol (# 600 manufactured by Sanyo Kasei) and 44% by weight of dimethylformamide were mixed and dissolved to prepare a stock solution for film formation. This stock solution is 36
It was a high-temperature phase-separated type undiluted solution that caused phase separation at a temperature of ℃ or higher. 3
The membrane-forming stock solution kept at 2 ° C. was made of 82% by weight of dimethylformamide and 18% by weight of water as an internal coagulation liquid from a double annular nozzle having an outer diameter of 1.0 mm and an inner diameter of 0.5 mm.
The mixed solution was discharged at the same time as the mixed solution at 8 ° C., and was allowed to run for 10 cm in humidified air at 50 ° C. and 90% RH.
It was immersed in water at ℃.

Next, dimethylformamide and polyethylene glycol were washed and extracted by washing with hot water at 50 ° C. and hot water at 95 ° C., then immersed in a 5% by weight aqueous glycerin solution, and wound up on a frame. Drying with warm air at 50 ° C. yielded a hollow fiber membrane having an outer diameter of 450 μm and an inner diameter of 320 μm. The 3,200 membranes were bundled and covered with moisture-permeable paper to form a bundle. The water permeability of this membrane is 1050
0 L / (m ² · hr · Kg / cm ² ), and the particle size of the fraction was 0.15 μm. The Tg measured by DSC is 1
68 ° C.

Production Example 2 17% by weight of polysulfone (P-1700), 34% by weight of polyethylene glycol (# 600) and 49% by weight of dimethylacetamide were mixed and dissolved to form a stock solution for film formation. This film forming stock solution was a homogeneous solution that did not cause phase separation between 10 ° C and 130 ° C. This film-forming stock solution kept at 50 ° C. was treated as an internal coagulation liquid from a double annular nozzle having an outer diameter of 0.5 mm and an inner diameter of 0.25 mm as dimethylacetamide 50% by weight,
The mixture was discharged at the same time as a mixed solution of 50% by weight of water at 50 ° C., allowed to run 10 cm in humidified air at 50 ° C. and 90% RH, and then immersed in 40 ° C. water as a coagulation bath. Then
Dimethylacetamide and polyethylene glycol were extracted and removed by washing with 50 ° C. hot water and 98 ° C. hot water.

Next, the membrane was impregnated with an 8 wt% glycerin aqueous solution, wound up around a frame, and dried with warm air at 50 ° C. to obtain a hollow fiber membrane having an outer diameter of 0.3 mm and an inner diameter of 0.2 mm. 9360 of these films were bundled and covered with moisture-permeable paper to form a bundle. The water permeability of this membrane is 720 L /
(M ² · hr · Kg / cm ² ), the molecular weight cut off was 32,000, and it was an excellent membrane that did not transmit bovine serum albumin. The Tg measured by DSC was 165 ° C.

Production Example 3 17% by weight of polysulfone (P-1700), 20.4% by weight of polyethylene glycol (# 600), 1.0% by weight of polyvinylpyrrolidone (K-90, manufactured by BASF), 61.6% of dimethylacetamide % By weight was mixed and dissolved to obtain a film forming stock solution. This membrane-forming stock solution kept at 50 ° C. was passed through a double annular nozzle having an outer diameter of 0.5 mm and an inner diameter of 0.25 mm as an internal coagulating liquid, polyvinylpyrrolidone (K-90).
0.3% by weight, dimethylacetamide 40% by weight, water 5
The mixture was discharged at the same time as a mixed solution of 9.7% by weight at 50 ° C., allowed to run 10 cm in humidified air at 50 ° C. and 90% RH, and then immersed in 50 ° C. water as a coagulation bath.

Next, dimethylacetamide, polyethylene glycol and excess polyvinylpyrrolidone were extracted by washing with warm water at 50 ° C. and washing with hot water at 90 ° C.
After impregnating the membrane in a t% aqueous glycerin solution, the membrane was wound up and dried with warm air at 50 ° C. to obtain a hollow fiber membrane having an outer diameter of 0.3 mm and an inner diameter of 0.2 mm. 9360 of these films were bundled and covered with moisture-permeable paper to form a bundle.

The water permeability of this membrane is 300 L / (m ² · hr)
Kg / cm ² ), the molecular weight cut off was 28,000, and the membrane was an excellent membrane that did not transmit bovine serum albumin. The residual amount of polyvinylpyrrolidone in the hollow fiber membrane was determined by NM.
It was 3.8 wt% as measured by R, and 22 wt% on the inner surface side and 18 wt% on the outer surface side as measured by ESCA. The Tg measured by DSC was 172 ° C.

Example 1 The bundles obtained in Production Examples 1 to 3 were placed in a hot-air circulation heating furnace controlled at 130 ° C. ± 3 ° C. for 5 minutes, 10 minutes, and 20 minutes.
The pieces were allowed to stand for 30, 60, 90, and 120 minutes to perform heat treatment. The relative humidity in the heat treatment machine was 0.6%. The temperature in the hollow fiber membrane bundle was measured by inserting a thermocouple at the center of the bundle. Tables 1 to 3 show the maximum temperatures in the bundle during the heat treatment time. The length of the hollow fiber before and after the heat treatment was measured, and the shrinkage of the hollow fiber membrane due to the heat treatment was calculated. The results are also shown in Tables 1 to 3.
Shown in Table 1 also shows the water permeability and the fractionation performance of the hollow fiber membrane after the heat treatment.

[0026]

[Table 1]

[0027]

[Table 2]

[0028]

[Table 3]

As shown in Tables 1 to 3, shrinkage of the hollow fiber membrane during high-pressure steam sterilization can be suppressed to 0.5% or less by performing a heat treatment at 130 ° C. for 10 minutes or more. . When the processing is performed for 90 minutes or more, the film performance after the processing is reduced, and the processing in the range of 10 to 90 minutes is appropriate.

Example 2 The temperature of the hot air circulating heating furnace was set at 150 ± 3 ° C. and 140 ± 3 ° C.
The same experiment as in Example 1 was performed except that the temperature was controlled at 120 ° C. and 120 ± 3 ° C. and the heat treatment time was set at 30 minutes. Table 4 shows the results. Under any of the heat treatment conditions, the decrease in the membrane performance after the heat treatment was small, and the shrinkage of the hollow fiber membrane during high-pressure steam sterilization could be kept at 0.8% or less.

[0031]

[Table 4]

Comparative Examples 1-21 The temperature of the hot air circulating heating furnace was 160 ± 3 ° C. and 110 ± 3 ° C.
The same experiment as in Example 1 was performed except that the temperature was controlled at 3 ° C. and the heat treatment times were set to 10 minutes and 30 minutes. Table 5 shows the results.
In the treatment at 110 ° C., the shrinkage of the hollow fiber membrane during high-pressure steam sterilization is not much different from that of the untreated one, and the effect of the heat treatment is not recognized. Further, when the heat treatment at 160 ° C. was performed, the hollow fiber membrane contracted greatly during the heat treatment, and the membrane performance was significantly reduced, which was not practical.

[0033]

[Table 5]

Comparative Examples 22 to 33 By introducing superheated steam, the relative humidity was 72% RH,
The bundle was placed in a heat treatment machine adjusted to 121 ° C. and heat treatment was performed. Table 6 shows the results. Although the hollow fiber membrane shrinks during steam sterilization when heat treatment is performed under high humidity conditions, it is small and good, but the hollow fiber membrane shrinks greatly during heat treatment despite treatment at a relatively low temperature, resulting in poor membrane performance. It was lowered and was not practical.

The same heat treatment was performed in a heat treatment machine adjusted to a relative humidity of 26% RH and 160 ° C. Table 6 shows the results. The heat treatment under high temperature and high humidity conditions significantly reduced the performance, and was not practical.

[0036]

[Table 6]

Example 3 Using the heat-treated bundles obtained in Examples and Comparative Examples, urethane was used as a potting resin and bonded to a polycarbonate housing by centrifugation to produce modules for plasma separation and dialysis. After washing by a conventional method, a leak check was performed, a module having no leak was filled with distilled water, and high-pressure steam sterilization was performed at 121 ° C. for 20 minutes. After sterilization, a leak check was performed again to confirm whether or not a leak occurred due to steam sterilization. Table 7 shows the results.

[0038]

[Table 7]

The results obtained using the hollow fiber membranes obtained in the examples were satisfactory without any occurrence of defects after high-pressure steam sterilization. On the other hand, as a result of using a hollow fiber membrane obtained by processing in a comparative example in which the processing temperature, humidity and time were inappropriate, defects were found after high-pressure steam sterilization. Since the medical membrane module is used as it is after sterilization, the occurrence of a defect is fatal.

[0040]

According to the present invention, it is possible to provide a method for treating a hollow fiber membrane having a small shrinkage upon heating. According to such a treatment method, since the occurrence of defects during high-pressure steam sterilization can be prevented, the safety of a medical membrane module using a hollow fiber membrane, such as a hemodialyzer, a hemofilter, a plasma separator, and an ascites filter, can be prevented. In addition, the merchantability can be improved.

Claims (4)

[Claims] 1. A hollow fiber membrane is spun into a film, subjected to a constant-humidity heat treatment in water, washed and removed of a residual solvent, further subjected to a constant-humidity heat treatment, and dried, and then subjected to any of (I) to (III). A method for treating a hollow fiber membrane, wherein the treatment is performed under conditions. RH ≦ 10% (I) Tg−60 ° C. ≦ T ≦ Tg−20 ° C. (II) 10 ≦ t ≦ 90 (III) where RH: Relative humidity of processing atmosphere (%) T: Dry heat treatment temperature (° C.) Tg: Glass transition temperature of hollow fiber membrane (° C) t: Dry heat treatment time (minute) 2. The method for treating a hollow fiber membrane according to claim 1, wherein the temperature and time of the constant-temperature and constant-humidity heat treatment in water or the constant-temperature moisture treatment are 80 to 90 ° C. for 2 minutes or more. 3. The method for treating a hollow fiber membrane according to claim 1, wherein the hollow fiber membrane is a hollow fiber membrane containing polysulfone as a main component. 4. The method for treating a hollow fiber membrane according to claim 1, wherein the hollow fiber membrane is a hydrophilic polymer.
A method for treating a hollow fiber membrane which is a hollow fiber membrane containing: