JPH0899026A - Preparation of hollow fiber membrane - Google Patents

Abstract

PURPOSE: To prepare stably a membrane even under the condition of a stock soln. where film formability is not kept by extruding a spinning stock soln. contg. a polymer-solvent mixed liq. exhibiting sol-gel change with change in temp. while air is fed into hollow parts from a spinneret and guiding the extruded filaments into a liq. bath to cool it into gelation. CONSTITUTION: In preparing a water-contg. gel hollow fiber membrane as a dialysis membrane used in artificial dialysis therapy, a spinning stock soln. contg. a polymer-solvent mixed liq. exhibiting sol-gel change with change in temp. is used. The stock soln. is extruded from a spinneret with a hollow pipe while air or an inert gas is fed into the hollow part and the extruded filaments are guided into a liq. bath and are cooled into gelation. In this case, the length from the lower face of the spinneret to the liq. bath is set to be 1-30mm. In addition, the polymer consists of an isotactic polymethyl methacrylate I and a syndiotactic polymethyl methacrylate S and the polymer compsn. in the range of 1<=I/S<=10 is used.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention has both high water permeability and excellent fractionation performance, which is composed of a polymer capable of forming a polymer-solvent mixture which exhibits a sol-gel change by a temperature change. The present invention relates to a method for producing a high performance hollow fiber membrane.
In particular, the present invention, together with its excellent biocompatibility, exhibits excellent performance for medical purposes, particularly for blood purification. further,
It can also be applied to general industrial applications such as food protein treatment and water treatment.

[0002]

2. Description of the Related Art With the widespread use of artificial dialysis treatment for renal failure patients, various complications such as carpal tunnel syndrome, bone disorders and anemia have become apparent in many dialysis patients over a long period of time.
Therefore, it could not be removed by the conventional film, for example β _2-
In order to remove medium-molecular weight substances such as microglobulin, investigations on high-performance membranes with relatively large pore diameters have been conducted. At the same time, on the other hand, for the purpose of so-called comfortable dialysis, proposals and improvements of various material membranes are being made for short-time dialysis and anti-thrombosis of modules.

On the other hand, various improvements have been made also to the gel-like hydrous polymethylmethacrylate synthetic membrane (Japanese Patent Publication No. 53-6249) having excellent biocompatibility. For example, solute permeability is improved by hydrophilization (Japanese Patent Publication No. 56-26443), removal performance of medium molecular weight substances is improved by increasing the pore size of the membrane (JP-A-59-147602), and phosphorus is introduced by introducing a specific group. And the selective removal (JP-A-59-166159).

Due to these improvements, the polymethylmethacrylate film is steadily effective in combination with its excellent biocompatibility. However, the dialysis membranes that have been proposed so far are still insufficient when compared to the renal function of healthy individuals, and it is necessary to further improve the ability to remove target substances.

[0005]

In order to further pursue such characteristics, a wider range of film forming conditions are required for the composition of the polymer and the stock solution, the spinning conditions, and the like.

Polymethylmethacrylate is an inherently hydrophobic polymer. However, polymethylmethacrylate with high isotacticity and polymethylmethacrylate with high syndiotacticity form a structural entanglement under certain conditions, forming a so-called stereocomplex. The hydrogel structure containing water molecules in the voids of this complex expresses the performance as a dialysis membrane.

It is known that this stereocomplex structure shows a sol-gel change with temperature. For example, in the method described in Japanese Patent Publication No. 53-6249, etc., when making a hydrogel gel polymethylmethacrylate hollow fiber membrane, first, the hollow sol discharged in the air is placed in an atmosphere below the gel point. It has been a basic practice to make the gel filaments to be formed surely by sufficiently retaining them or by forcibly supplying cold air, and then introducing them into a coagulation bath to prepare a hydrogel hollow fiber membrane. Therefore, in order to produce a high quality hollow fiber membrane, the characteristics of the discharged sol are very important points, and in particular, its viscoelastic behavior is greatly involved in the hollow fiber morphology. Therefore, even if an attempt was made to change the conditions such as the polymer composition or the concentration of the undiluted solution in order to obtain a certain target property, the spinnable conditions were actually limited, and the purpose could not be sufficiently achieved.

The present invention is intended to solve the drawbacks of the prior art, and to provide a method for producing a hollow fiber membrane in which the shape of the hollow fiber membrane can be easily maintained and a wide range of prevention conditions can be set. To aim.

[0009]

The present invention has the following constitution in order to achieve the above object.

"A spinning stock solution containing a polymer-solvent mixed solution which exhibits a sol-gel change due to a temperature change is passed through a spinneret consisting of an annular orifice having a hollow tube in the spinneret hole to air or an inert gas in the hollow part. The method for producing a hollow fiber membrane is characterized in that, while injecting, is discharged into the air or an inert gas, and then the discharged yarn is introduced into a liquid bath to be cooled and gelled. ”That is, the present inventor Et al., The medium for cooling the sol filament discharged in the air does not necessarily have to be a gas, and even when it is a liquid, it is possible to form a hydrogel structure as a dialysis membrane. In addition, the large heat exchange capacity of the liquid enables quick gelation and fixation of the discharged sol filaments, makes it easier to maintain the shape of the hollow filaments, and supports various ejection sol conditions. Among the target characteristics The inventors have found that an empty fiber membrane can be produced and have reached the present invention.

The present invention will be described in detail below.

In the present invention, examples of the polymer exhibiting sol-gel change depending on temperature change include isotactic-polymethylmethacrylate and syndiotactic polymethacrylic acid, syndiotactic-polymethylmethacrylate and polyvinyl chloride. , And isotactic-polymethylmethacrylate and syndiotactic-polymethylmethacrylate.

Among them, in polymethylmethacrylate, in order for the solution system to show an effective sol-gel change due to temperature change, it is necessary to contain an isotactic portion and a syndiotactic portion therein. .
To obtain such a composition, a polymer having high isotacticity and a polymer having high syndiotacticity are usually mixed.

Isotactic polymethylmethacrylate has an isotactic structure (triad display).
Of 50% or more, preferably 70% or more is used. The three-dimensional structure of polymethylmethacrylate can be quantitatively determined by the nuclear magnetic resonance absorption method. Isotactic polymethylmethacrylate is generally obtained by polymerization using a Grignard reagent or an organometallic compound such as alkyllithium. By such a method, it is possible to obtain a polymer having an isotactic structure content of 90% or more. is there.

On the other hand, syndiotactic polymethylmethacrylate having high syndiotacticity can be obtained by ordinary radical polymerization. In this case, carboxyl group,
One or more types of vinyl monomers containing anionic groups such as sulfonic acid groups or quaternary ammonium groups, cationic groups such as amino groups, and nonionic groups such as hydroxyethylmethacrylate and acrylamide, etc. Polymerization is also an extremely effective means for enhancing the selective permeability and biocompatibility of the membrane. Further, polymethylmethacrylate homopolymers, polymers having different molecular weights, or copolymers of different types may be mixed and used, if necessary, within a range in which the solution causes a sol-gel change due to a temperature change. Will be performed.

Further, the molecular weight of polymethylmethacrylate is usually preferably 100,000 or more in consideration of the desired membrane performance, mechanical properties, and spinnability of the hollow fiber membrane.

As the solvent of the spinning dope used in the present invention, any solvent capable of dissolving the polymer exhibiting the sol-gel change can be used. However, when the spinning dope is cooled, it is at an appropriate temperature. A gelling solvent is preferably used.
A feature of the present invention is that an unstable hollow fiber filament discharged in a liquid state is cooled in a liquid bath to surely cause a sol-gel change, whereby the hollow form thereof can be reliably retained.
Further, since water is preferably used as the coagulant for removing the solvent from the coagulated yarn to obtain a product, a solvent that is easily replaced with water is particularly preferable. For this reason, dimethylsulfoxide, dimethylformamide, acetonitrile, acetic acid, acetone, methyl ethyl ketone, and mutual mixtures thereof are used.

The polymer concentration of the spinning dope also affects the membrane performance, the mechanical properties of the membrane, or the spinnability of the hollow fiber membrane, like the molecular weight. According to the present invention, the conventional spinning method can be applied. By comparison, a very wide range of condition choices is possible. Considering the performance and mechanical properties of the obtained membrane, the polymer concentration in the spinning dope is preferably set in the range of 5 to 30% by weight, and more preferably 10 to 30% by weight.

Further, in order to control the pore size of the membrane, adding a third additive such as polyhydric alcohol, water, salt or the like is also a commonly practiced means.

The viscosity of the spinning dope thus obtained is
It is a factor that is deeply related to the spinnability, and is preferably determined in consideration of the shape and size of the die to be used, a controllable temperature range, and the sol-gel change temperature which is a feature of the present invention. Usually, it is preferably 10 to 8,000 poise, and more preferably 100 to 3,000 poise. That is, it is possible to set the optimum spinning stock solution conditions by appropriately selecting the polymer concentration and the molecular weight.

[0021] Usually, the dry-wet spinning method used for spinning a hollow fiber membrane is a method in which a discharged yarn is stretched in the air, set to a predetermined size, and then introduced into a coagulation bath for coagulation / desolvation. And is generally widely adopted.

The stable holding of the hollow fiber size, which is a major feature of the present invention, is affected by the distance from the discharge nozzle to the bath liquid, that is, the length of the so-called dry portion (hereinafter referred to as the dry length). That is, in order to extend the shape of the discharged sol to a desired size, it is preferable to draft in a sol state at a certain distance in the air. On the other hand, since a rapid draft lowers the stability of yarn production, it is preferable that the draft is taken to some extent. At the same time, if the dry length is too long, the deformation of the sol tends to be unstable and the dimensional stability of the hollow fiber tends to deteriorate. Therefore, the dry length is preferably 1 mm or more and 30 mm or less, and more preferably 2 mm or more and 20 mm.
It is set below.

The liquid bath for gelating the discharged sol and fixing the shape of the hollow fiber may only be gelled, but it may be advantageous in the process to perform the desolvation simultaneously with gelation. Mostly used as a coagulation bath. Therefore, its composition and especially its temperature can also influence the permeation properties of the hollow fiber. Generally, as the coagulation bath temperature increases, the permeability of the membrane increases, but the dimensional stability tends to decrease, so conditions are selected according to the characteristics of the target hollow fiber, and usually 5 to 70 ° C. Is more preferable, and 20 to 50 ° C. is more preferable.

The hollow fiber gel thus obtained is sufficiently washed with water, dried by applying a moisturizing agent such as glycerin so as not to destroy its membrane structure, and then wound into a hollow fiber bundle.

The obtained hollow fiber bundle is loaded into a predetermined case by a usual method and then modularized with a sealing agent such as polyurethane. Further, it is washed and sterilized to be used for medical purposes such as blood purification and further filtration separation.

[0026]

EXAMPLES The present invention will be described in detail below with reference to examples.

<Measurement of Water Permeability> The water permeability in the present invention is determined by flowing pure water at 37 ° C. into the hollow portion of the hollow fiber membrane, and at that time, the amount of water that has permeated through the hollow fiber membrane and is discharged to the outside. The effective area, time, and pressure are used for unit conversion and evaluated.

<Evaluation of protein permeability> A mini module having a membrane area of about 60 cm ² was prepared and the protein concentration was 7.5 g / dL inside the hollow fiber.
Of bovine plasma is supplied with a transmembrane pressure difference of about 100 mmHg and a flow rate of 0.6 mL / min. The albumin concentration in the obtained filtrate is determined by using Albsticks test paper (made by Miles Sankyo Co., Ltd.).

<Measurement of Permeability> The permeation performance in the present invention is generally represented by the clearance used in the performance evaluation of artificial kidneys, and is summarized as follows. Let CBi be the blood-side inlet concentration of a certain solute, CBo be the outlet concentration, CDi be the dialysate-side inlet concentration, QBi be the blood-side inlet flow rate of the artificial kidney, and QBo be the outlet flow rate. .

Clearance = (QBi × CBi−QBo × CB
o) / (CBi-CDi) With respect to urea and inorganic phosphorus, the permeation performance is evaluated by this method.

Example 1 Isotactic (hereinafter abbreviated as iso-) polymethyl methacrylate (hereinafter abbreviated as PMMA) polymerized with a Grineer reagent 6
00 parts, a copolymer of methyl methacrylate and sodium p-styrenesulfonate (p-SSS) prepared by ordinary radical polymerization (p-SSS: 2.8 mol%) 2448 parts, and syndiotactic by radical polymerization (Abbreviated as syn-) PM
550 parts of MA was dissolved in 16400 parts of dimethyl sulfoxide (hereinafter abbreviated as DMSO) at 110 ° C. to obtain a spinning dope having a viscosity of 563 poise. This stock solution was put into a ring slit type die with an outer diameter of 0.65φ and an inner diameter of 0.25φ at 2.4 ° C at 110 ° C.
Discharge at a rate of g / min, dry length 8 mm, and water consisting of 40 ° C
Led to the coagulation bath. Further, washing with water and replacement with glycerin were performed to collect a hollow fiber bundle. The inner diameter of this hollow fiber is 211μ
m, film thickness 38 μm, and outer diameter range ROD is 12 μm.
It was shown that there was little unevenness in m and hollow fiber dimensions. The water permeability of this hollow fiber membrane was 66 mL / hr / mmHg / m ² . A module having a membrane area of 1.7 m ² was prepared from this bundle, washed and γ-ray sterilized to evaluate the permeation performance. As a result, the clearance of urea and inorganic phosphorus was QBi200.
At mL / min, it showed high performance of 193 mL / min and 171 mL / min.

Example 2 38 parts of iso-PMMA and syn-PMM by radical polymerization
A188 parts were dissolved in 1275 parts DMSO at 105 ° C. to give a clear stock solution with a viscosity of 445 poise. Using this stock solution, in the same manner as in Example 1, spinning was carried out with a dry length of 5 mm to obtain a hollow fiber having an inner diameter of 269 μm and a film thickness of 36 μm. The water permeability of this hollow fiber is 106 mL / hr / mmHg /
m ² and protein permeability of bovine plasma were ±, and no protein leak was observed in spite of high water permeability.

Comparative Example 1 Using the same spinning dope as shown in Example 1, a dry length of 4 was obtained.
Cooling gelation was carried out with cold air of 50 mm and 12 ° C. to obtain a hollow fiber bundle. The water permeability of the hollow fiber membrane is 48 mL / hr / mmHg / m ²
However, the average inner diameter could not be 160 μm or more, and the hollow fiber could not be used as a blood purification module because the hollow fiber size was too uneven.

Comparative Example 2 As in Example 2, 880 parts of iso-PMMA, syn-PM
A stock solution for spinning was prepared by dissolving 4400 parts of MA and 16720 parts of DMSO. Using this stock solution, according to the same method as in Comparative Example 1, a dry gel length of 450 mm and cooling gelation spinning with cold air of 15 ° C. were performed. The water permeability of the obtained hollow fiber was 52 mL / hr / mmHg / m ² and the dimensional unevenness was slightly small, but the protein permeability was ++ as evaluated by bovine plasma and protein leak was observed. .

Example 3 Methyl methacrylate (hereinafter abbreviated as MMA), methoxy polyethylene glycol methacrylate (hereinafter abbreviated as MPEG) having an average degree of polymerization of polyethylene glycol of 90 and vinyl acetate (hereinafter abbreviated as VAc) were added to azobisdimethyl valero. Ordinary radical copolymerization was carried out using nitrile as an initiator to obtain a hydrophilic polymer. When the composition of the copolymerization component was confirmed by NMR, the weight composition ratio of MMA, MPEG and VAc was 36, 36 and 28 weight percent. 42 parts of this hydrophilic polymer and 70 parts of iso-PMMA, 98 parts of syn-PMMA having an average molecular weight of 400,000 by radical polymerization, methyl methacrylate prepared by ordinary radical polymerization and sodium p-styrenesulfonate (p-SSS) Polymer (p
-SSS: 1.5mol%, average molecular weight 500,000) 252 parts and 13
It was dissolved in 77 parts of DMSO at 105 ° C. to obtain a clear stock solution having a viscosity of 523 poise. Using this stock solution, in the same manner as in Example 1, spinning was performed with a dry length of 4 mm to obtain a hollow fiber having an inner diameter of 214 μm and a film thickness of 36 μm. The water permeability of this hollow fiber was 75 mL / hr / mmHg / m ² , and the protein permeability by bovine plasma evaluation was ±. Despite the high water permeability, no protein leak was observed. From this bundle, the membrane area 0.2 m ²
The module was prepared, washed, and γ-ray sterilized to evaluate the permeation performance. As a result, the clearance of urea and inorganic phosphorus was 47 at QBi = 50 mL / min.
It showed high performance at mL / min and 39 mL / min.

Comparative Example 3 Using a spinning dope as described in Example 3, a dry length of 1 was used.
A hollow fiber bundle was obtained by cooling gelation with 90 mm and cold air at 13 ° C. Water permeability of hollow fiber membrane is 73 mL / hr / mmHg / m
^The preferred value was ² , but the protein permeability was +++ as evaluated by bovine plasma, and protein leak was observed.

Example 4 42 parts of the hydrophilic polymer of Example 3 and 70 parts of iso-PMMA, and syn-PM having an average molecular weight of 1.4 million by radical polymerization.
MA 56 parts, methyl methacrylate prepared by conventional radical polymerization and sodium p-styrenesulfonate (p-SSS)
Copolymer with (p-SSS: 1.5mol%, average molecular weight 1.4 million)
252 parts and 1377 parts of DMSO were dissolved at 105 ° C. to obtain a clear stock solution having a viscosity of 2548 poise. Using this stock solution, a dry length of 12 was obtained in the same manner as in Example 1.
Spinning was performed at a thickness of mm to obtain a hollow fiber having an inner diameter of 197 μm and a film thickness of 37 μm. The water permeability of this hollow fiber is 56 mL / hr / mmHg / m.
^{2. The} protein permeability of the bovine plasma was negative and no protein leak was observed.

[0038]

EFFECTS OF THE INVENTION According to the present invention, it is possible to form a stable film even under undiluted conditions that could not be adopted because the film forming property cannot be maintained while having excellent solute permeability and fractionation performance.
It facilitates modification of various polymer materials and introduction of functional groups for imparting excellent biocompatibility. The membrane thus obtained can be applied not only to the medical field but also to general industrial applications, and its application range can be expanded.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Hiroyuki Sugaya 1-1-1, Sonoyama, Otsu City, Shiga Prefecture Toray Co., Ltd. Shiga Plant

Claims (4)

[Claims] 1. A spinning dope containing a polymer-solvent mixture which exhibits a sol-gel change due to temperature change is fed from a spinneret consisting of an annular orifice having a hollow tube inside the spinneret to air or inert gas in the hollow part. A method for producing a hollow fiber membrane, which comprises discharging gas into air or an inert gas while injecting the gas, and then introducing the discharged yarn into a liquid bath for gelation by cooling. 2. The length from the lower surface of the die to the liquid bath is 1 mm.
The method for producing a hollow fiber membrane according to claim 1, wherein the length is 30 mm or less. 3. The polymer-solvent mixture, wherein the polymer is isotactic polymethylmethacrylate (I).
And syndiotactic polymethylmethacrylate (S)
And the ratio (I / S) is 0.1 or more,
It is in the range of 10 or less, The manufacturing method of the hollow fiber membrane of Claim 1 or Claim 2 characterized by the above-mentioned. 4. The liquid bath for cooling and gelling the discharged yarn is a coagulating bath.
A method for producing a hollow fiber membrane according to item.