JP2002143654A - Hollow fiber membrane and its manufacturing method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hollow fiber membrane which is excellent in separativeness for middle and high molecular weight substances and permeability of low molecular weight substance. SOLUTION: This hollow fiber membrane has a dense layer on the inner surface thereof and a porous layer having voids on the parts besides the dense layer, therein, the porosity is 60-90%, and in a dry state, the distance from the inner surface to the voids is 3-50% of the maximum film thickness, and therefore, the excellent separativeness for middle or high molecular weight substance and permeability of low molecular weight substance can be obtained.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hollow fiber membrane, and more particularly to a hollow fiber membrane used for a blood purification membrane such as a hemodialysis membrane, a hemodiafiltration membrane, a blood filtration membrane, a continuous slow blood filtration membrane, and the like. About the method.

[0002]

2. Description of the Related Art The technique of using a hollow fiber membrane having selective permeability in a separation operation has been put to practical use in the medical field, the industrial field, and the like. A hollow fiber membrane is required to have high permeability and high fractionability, and is an asymmetric membrane having a dense layer on the inner surface that mainly governs fractionation and permeability, and a porous layer that supports the same. Those with a structure are common. For example, an ethylene-vinyl alcohol having an asymmetric structure including a dense layer and a porous layer (hereinafter, ethylene-vinyl alcohol is referred to as “E
VA ”. ) -Based polymer (hereinafter, a hollow fiber membrane formed of an EVA-based polymer is abbreviated as “EVA hollow fiber membrane”).
602, JP-A-58-45239, JP-A-5-42208, etc.).

[0003]

In recent years, there has been an increasing tendency in various fields to require higher performance for hollow fiber membranes. For example, in hemodialysis treatment, not only are low molecular weight substances such as urea and creatinine removed, but also, for example, β ₂ -microglobulin (molecular weight 1180)
It is desired to remove medium and high molecular weight substances such as 0). However, conventional hollow fiber membranes have not always been satisfactory in the removal performance of medium-high molecular weight substances.

[0004] In view of the above problems, an object of the present invention is to provide a hollow fiber membrane excellent in the fractionability of a medium-high molecular weight substance and the permeability of a low molecular weight substance, and a method for producing the same.

[0005]

Means for Solving the Problems The inventors of the present invention have made intensive efforts to achieve such an object, and as a result, before the extrusion, the film forming stock solution was temporarily maintained at a temperature lower than the phase separation temperature, or Is extruded so as to receive a draft of 0.5 to 4 times, thereby making it possible to control the distance from the inner surface of the hollow fiber to the void and the porosity, and to provide a hollow fiber excellent in fractionation and permeability. The inventors have found that a film can be obtained, and have reached the present invention.

That is, the present invention has a dense layer on the inner surface, a porous layer having voids in portions other than the dense layer, a porosity of 60 to 90%, and a dry state.
A hollow fiber membrane characterized in that the distance from the inner surface to the void is 3 to 50% of the maximum film thickness.

[0007] The present invention also provides a film-forming stock solution which is transparent and uniform at high temperatures but undergoes phase separation when the temperature is lowered, and injects the film-forming stock solution into the inside of a double annular nozzle while injecting a hollow forming agent. A method for producing a hollow fiber membrane, in which a hollow fiber membrane extruded from the double annular nozzle is passed through the air and then introduced into a water bath; ) and (2): 5 ≦ LST ≦ 40 (1) LST ≦ T D ≦ LST + 40 (2) [ wherein, LST phase separation temperature of the film forming dope (℃), T _D is the film-forming stock solution temperature (℃ ). Is satisfied, the temperature of the film forming stock solution is adjusted so that the film forming stock solution is extruded from the double annular nozzle.
The relationship of the above equation (2) is satisfied up to a minute before. [However, S satisfies the relationship of 0 <S ≦ 1440.] And then until extrusion, LST-20 ≦ T _D <LST (3) (where LST and T _D are as defined above), and the film is formed. was extruded stock solution, dual annular temperature of the air passing the extruded hollow fiber membrane from the nozzle following formula _{(4): T a ≦ LST} (4) [ wherein, T _a is a double annular nozzle Indicates the temperature (° C.) of the air passing through the extruded hollow fiber membrane, and LST is as defined above. ], And a method for producing a hollow fiber membrane.

[0008] Further, the present invention provides a membrane-forming stock solution which is transparent and uniform at high temperatures but undergoes phase separation when the temperature is lowered.
The hollow fiber membrane is extruded while injecting a hollow forming agent into the inside of the double annular nozzle, and the hollow fiber membrane extruded from the double annular nozzle is passed through the air and then introduced into a water bath. a method of manufacturing, the prepared film-forming solution is the following formula (1) and (2): 5 ≦ LST ≦ 40 (1) LST ≦ T D ≦ LST + 40 (2) [ wherein, LST is film formation phase separation temperature of the stock solution (℃), T _D represents the film formation dope temperature (° C.). Is satisfied, and the temperature of the film forming stock solution satisfies the relationship of the above formula (2) until the film forming stock solution is extruded from the double annular nozzle. after extrusion, the film-forming solution was extruded to receive the fold of the draft, the temperature is below the formula air passing the hollow fiber membrane extruded from the double annular nozzle _{(4): T a ≦ LST} (4) [ In the formula, T _A represents the temperature (° C.) of air passing through the hollow fiber membrane extruded from the double annular nozzle, and LST is as defined above. ], And a method for producing a hollow fiber membrane.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The hollow fiber membrane of the present invention has a dense layer on the inner surface, and has a porous layer having voids in portions other than the dense layer. The above-mentioned dense layer means a region having a pore size of 5 to 50 nm, and the pore size is obtained by observing the surface of the dense layer with an electron microscope (magnification: 60000). The thickness of the dense layer is preferably in the range of 0.1 to 2 μm from the viewpoint that defects are not easily generated in the dense layer, the rejection of albumin is high, and the permeability of medium-high molecular weight substances is high. More preferably, it is in the range of 0.1 to 1 μm. The porous layer in a portion other than the dense layer is a layer supporting the hollow fiber membrane, and usually has a void having a pore diameter of 100 nm or more. The shape of the void is not particularly limited as long as the effect on the permeability of the medium-high molecular weight substance is small, and any shape such as a mesh or a macro void can be used.

[0010] The porosity of the hollow fiber membrane of the present invention is 60
９０90%, preferably 65-85%. By setting the porosity within the above range, a hollow fiber membrane having high permeability and high mechanical strength can be obtained.
Here, the porosity is determined by the following equation. Porosity _{(%) = {(W W} -W D) / ρ W} / {W D ρ E -
_{(W W -W D) / ρ} W} × 100 W W: weight W _D hydrous film: weight of dry membrane [rho _W: Water density [rho _E: a specific gravity of EVA

The distance from the inner surface of the hollow fiber membrane to the void in the dry state of the present invention is in the range of 3 to 50% of the maximum film thickness, and preferably in the range of 3 to 40%.
By setting the distance from the inner surface to the void within the above range, a hollow fiber membrane having high fractionability and permeability can be obtained.

The hollow fiber membrane of the present invention has a hollow fiber shape, and preferably has a film thickness in the range of 3 to 2000 μm, more preferably 10 to 1000 μm. The outer diameter of the hollow fiber membrane is preferably in the range of 40 to 3000 μm, and more preferably in the range of 100 to 2000 μm.

Hereinafter, the method for producing the hollow fiber membrane of the present invention will be described. First, a film-forming stock solution is prepared by dissolving at least one kind of polymer as a film material in a solvent. The polymer used as the membrane material is not particularly limited, and examples thereof include a polysulfone polymer, a polyacrylonitrile polymer, a cellulose polymer such as cellulose acetate, a polyamide polymer, a polycarbonate polymer, and an EVA polymer. A polyvinyl alcohol-based polymer such as a polymer can be used. When used for medical applications, EVA-based polymers are preferred because they are excellent in biocompatibility and chemical stability and have a small amount of eluted substances.

The above EVA polymer preferably has an ethylene content of 10 to 60 mol% and a saponification degree of 95 mol% or more, and has an ethylene content of 20 to 55 mol%.
Those having a saponification degree of 97 mol% or more are more preferable. The polymerization form of the EVA polymer may be any of random, block, and graft. The EVA polymer may be copolymerized with a polymerizable monomer such as methacrylic acid, vinyl chloride, methyl methacrylate, and acrylonitrile at a ratio of 15 mol% or less.

Solvents for dissolving the above polymer include dimethyl sulfoxide (DMSO), N, N-dimethylacetamide (DMAc), N-methylpyrrolidone (NM
P) and mixed solvents containing these as components. When using an EVA polymer as a film material,
It is preferable to use DMSO because a hollow fiber membrane having the membrane structure and performance desired in the present invention can be easily obtained and the toxicity is relatively low.

The concentration of the polymer in the stock solution is 5 to
It is preferably in the range of 50% by weight, more preferably in the range of 10 to 30% by weight. If the concentration of the polymer is out of this range, the permeability tends to decrease if the concentration is too high, and if the concentration is too low, the viscosity of the stock solution becomes low and the spinnability becomes poor, or the mechanical strength of the membrane decreases. May be.

An additive may be added to the film forming stock solution in order to adjust the phase separation temperature and viscosity. Examples of additives include water, alcohols such as methanol, ethanol, glycerin, ethylene glycol and diethylene glycol, ketones such as acetone and methyl ethyl ketone, polyethylene glycol, chitosan, chitin, dextran, polymers such as polyvinylpyrrolidone, lithium chloride, Sodium chloride, calcium chloride, lithium acetate,
Salts such as sodium sulfate and sodium hydroxide can be exemplified, and among these, water which is free from concerns about volatility and toxicity is preferable. In addition, it is preferable to add a lithium salt in order to promote solidification and form a desired dense layer on the inner surface. When a highly hydrophobic polymer such as polysulfone is used as a membrane material, it is preferable to add a hydrophilic polymer such as polyethylene glycol or polyvinylpyrrolidone in order to increase the hydrophilicity of the entire membrane.

The stock solution for film formation in the present invention is transparent and uniform at a high temperature, but causes phase separation when the temperature is lowered. The temperature (° C.) at which the phase separation occurs is represented by the following formula (1): 5 ≦ LST ≦ 40 (1) [where LST represents the phase separation temperature (° C.) of the membrane-forming stock solution. Is satisfied. For this purpose, it is preferable that the concentration of the additive in the film forming stock solution is 20% by weight or less.
When the additive concentration exceeds 20% by weight, the polymer constituting the hollow fiber membrane may not be dissolved. Here, the phase separation temperature means a temperature at which the stock solution becomes cloudy when the temperature is reduced at a rate of 1 ° C./minute from 90 ° C.

In order to obtain a hollow fiber membrane having the desired membrane structure and performance in the present invention, it is preferable to employ a dry-wet membrane forming method as a film forming method, and to form a hollow forming agent inside a double annular nozzle. The film forming stock solution is extruded into the air while injecting, and solidified from the inner surface to form a dense layer on the inner surface, and then introduced into a water bath. In a wet film forming method in which a film forming solution is directly extruded into a water bath and solidified, solidification occurs not only on the inner surface but also on the outer surface, so that a dense layer is easily formed on the outer surface.

In order to form a desired dense layer on the inner surface, it is necessary to promote coagulation, and it is preferable to use a solution having an action of coagulating a polymer as a film material as a hollow forming agent. preferable. The hollow-forming agent can be used without any particular limitation as long as it has a function of coagulating a polymer serving as a membrane material and is miscible with the above-mentioned solvent. As such a hollow forming agent, an aqueous medium is usually used, for example, water; DMSO, DMAc, NM
A mixture of water and a solvent soluble in water, such as P and alcohol, can be mentioned, and an aqueous solution containing 60% by weight or less of water and the above-mentioned solvent is preferable. When the amount of the solvent exceeds 60% by weight, the permeability of the obtained membrane is increased, but the fractionability of the membrane is hardly increased, and the membrane formation may be difficult. Also, if necessary, an aqueous solution containing an inorganic salt such as lithium chloride, sodium chloride, calcium chloride, lithium acetate, sodium sulfate, and sodium hydroxide, or a polymer such as polyethylene glycol, chitosan, chitin, dextran, or polyvinylpyrrolidone. Etc. can also be used.

The temperature of the prepared film-forming stock solution is represented by the following formula (2): LST ≦ T _D ≦ LST + 40 (2) [wherein LST is the phase separation temperature (° C.) of the film-forming stock solution, and T _D is the film forming film. Indicates the temperature (° C.) of the stock solution. Is satisfied. If the temperature of the membrane forming solution is higher than LST + 40 ° C., the resulting hollow fiber membrane will have a reduced albumin rejection rate and will be difficult to form.

The temperature of the film forming stock solution satisfies the relationship of the above formula (2) until S minutes before the film forming stock solution is extruded from the double annular nozzle [where S satisfies the relationship of 0 <S ≦ 1440. I do. ], The following equation then to the extrusion (3): LST-20 ≦ T D <LST (3) (. Wherein, LST and T _D are as respectively defined above) satisfy the relation:. By satisfying such conditions, it is possible to obtain a hollow fiber membrane excellent in the fractionability of a medium-high molecular weight substance. When the above S is longer than 1440 minutes or in the above formula (3), the temperature (T _D ) of the stock solution is lower than LST−20 ° C., the film formation becomes difficult. The difference (ΔT _D ) between the temperature of the film forming solution before S minutes before extruding the film forming solution from the double annular nozzle and the temperature of the film forming solution for S minutes before extrusion is 0 <ΔT _D ≦ 50. Is preferably satisfied.

In the present invention, after extruding the stock solution, the temperature of the air passing through the hollow fiber membrane extruded from the double annular nozzle is determined by the following equation (4): T _A ≦ LST (4) In the equation, T _A represents the temperature (° C.) of air passing through the hollow fiber membrane extruded from the double annular nozzle, and LST is as defined above. Is satisfied. When the temperature (T _A ) is higher than the phase separation temperature (LST), the rejection of albumin of the obtained hollow fiber membrane may decrease, and the membrane may be difficult to form.

Further, the hollow fiber membrane of the present invention satisfies the relationship of the above-mentioned formula (2) until the temperature of the stock solution for film formation until S minutes before the stock solution is extruded from the double annular nozzle. In addition to the above-described method of controlling so as to satisfy the relationship of the above formula (3), the temperature of the stock solution is controlled by the relationship of the above formula (2) until the stock solution is extruded from the double annular nozzle. And a method of extruding the film forming stock solution so as to receive a draft of 0.5 to 4 times at the time of extrusion. The draft ratio is preferably in the range of 0.6 to 3 times. Such a draft magnification can be achieved by adjusting the film thickness, the nozzle diameter, and the like. That is,
Draft magnification decreases if the film thickness is increased with the same nozzle,
Draft magnification can be increased by making it thinner. Also,
Regarding the nozzle diameter, if the cross-sectional area from which the undiluted solution flows is increased, the draft magnification decreases, and if it is reduced, the draft magnification can be increased.

The hollow fiber membrane thus obtained is composed of water,
It is washed with warm water or the like, stretched and heat-treated if necessary, and finally dried. Thereafter, the module is appropriately incorporated into a module by a known method, and is used for various uses such as medical uses such as hemodialysis and plasma separation and industrial uses such as wastewater treatment.

[0026]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. In the examples, a hemodialysis membrane is exemplified, but the present invention is not limited to this.
The overall mass transfer coefficient of myoglobin and the inhibition rate of albumin were measured by the following methods, respectively. The larger the overall mass transfer coefficient of myoglobin and the higher the rejection of albumin, the more the membrane intended for the present invention is excellent in the fractionability of medium-high molecular weight substances and the permeability of low molecular weight substances.

Measurement of the overall mass transfer coefficient of myoglobin and the rejection of albumin: These are the dialyzer performance evaluation criteria (Takeshi Sato et al .: Functions and adaptations of various blood purification methods-Performance evaluation method and function classification of blood purifiers, "Dialysis Society Magazine",
29 (8): 1231～1245,1996) according sought, the overall mass transfer coefficient of myoglobin is calculated by the following equation from the clearance measured in aqueous (filtration flow _{Q F '= 0mL / min /} m 2), albumin The inhibition was measured in a bovine plasma system (Q _F ′ = 10 mL / min / m ² ). K = Q _B / A × (1-Z) × ln (1-E × Z) / (1
_{-E) E = CL / Q B} Z = Q B / Q D K: overall mass transfer coefficient (cm / min) CL: Clearance (mL / min) Q _B: blood side inlet flow (mL / min) Q _D: Dialysate side inlet flow rate (mL / min)

Example 1 EVA-based polymer having an ethylene content of 47 mol% and a saponification degree of 99% (EVAL ES-G110 manufactured by Kuraray Co., Ltd.)
A) 15 parts by weight, dimethyl sulfoxide (DMSO) 7
8 parts by weight, 5 parts by weight of water and 2 parts by weight of lithium acetate at 90 ° C.
And heat-dissolved to obtain a film-forming stock solution. L of the obtained membrane-forming stock solution
ST was 29 ° C. Immediately before extruding the stock solution at 40 ° C. (T _D ) from the double annular nozzle, 2 minutes (S) about 25 ° C.
After holding the (T _D), while injecting water into the interior of the double annular nozzle, extruding the film-forming solution of 25 ℃ (T _D) to receive 5.6 times the draft, 10 ° C. (T _A ) And introduced into a water bath. Thereafter, washing with water, wet heat treatment, drying and dry heat treatment were performed according to a conventional method to obtain a dry hollow fiber membrane. The inner diameter of the hollow fiber was 176 μm, and the film thickness was 49 μm. The film forming conditions are shown in Table 1, and the obtained film was subjected to electron microscopy (6
Table 2 shows the structure and performance observed at 0000 ×).

Example 2 EVA-based polymer having an ethylene content of 32 mol% and a saponification degree of 99% (EVAL EC-F100 manufactured by Kuraray Co., Ltd.)
A) 17 parts by weight, 71 parts by weight of DMSO, 10 parts by weight of water,
Lithium chloride (2 parts by weight) was heated and dissolved at 90 ° C. to obtain a film forming stock solution. The LST of the obtained membrane-forming stock solution was 30 ° C.
While a DMSO / water (30/70) solution was injected into the inside of the double annular nozzle, 2.4 parts of the stock solution at 30 ° C. (T _D ) was added.
Extrusion to receive twice the draft, 10 ℃ (T _A)
And introduced into a water bath. Thereafter, washing with water, wet heat treatment, drying and dry heat treatment were performed according to a conventional method to obtain a dry hollow fiber membrane. The inner diameter of the hollow fiber is 175 μm and the film thickness is 45 μ
m. Table 1 shows the film forming conditions, and Table 2 shows the structure and performance of the obtained film observed with an electron microscope (magnification: 60000).

[0030]

[Table 1]

[0031]

[Table 2]

[0032]

According to the present invention, there is provided a permselective hollow fiber membrane excellent in the fractionability of medium-high molecular weight substances and the permeability of low molecular weight substances.

 ──────────────────────────────────────────────────の Continued on the front page (72) Inventor Yoichi Matsumoto 1621 Sakurazu, Kurashiki-shi, Okayama Pref.Kuraray Co., Ltd. (72) Inventor Masato Takai 1621 Sakurazu, Kurashiki-shi, Okayama Pref. Kunihiko Nakata 1621 Sakurazu, Kurashiki-shi, Okayama Prefecture Kuraray Co., Ltd. (72) Inventor Hitoshi Tsuruta 2045, Sakurazu, Kurashiki-shi, Okayama Prefecture Kuraray Co., Ltd. F-term (reference) 4D006 GA13 MA01 MA24 MB01 MC34X NA23 NA28 NA29 PB70 PC41 4L035 AA09 BB04 BB06 DD03 DD07 EE20

Claims (5)

[Claims] 1. A dense layer having an inner surface, a porous layer having voids in portions other than the dense layer, and a porosity of 60 to 9
0%, and the distance from the inner surface to the void in a dry state is 3 to 50% of the maximum film thickness. 2. The hollow fiber membrane according to claim 1, comprising an ethylene-vinyl alcohol polymer. 3. An ethylene-vinyl alcohol polymer having an ethylene content of 10 to 60% and a saponification degree of 95 mol%.
The hollow fiber membrane according to claim 2, which is the above-mentioned ethylene-vinyl alcohol-based polymer. 4. A film-forming stock solution that is transparent and uniform at high temperature but undergoes phase separation when the temperature is lowered, and extruding the film-forming stock solution while injecting a hollow forming agent into the inside of a double annular nozzle,
A method for producing a hollow fiber membrane, in which a hollow fiber membrane extruded from the double annular nozzle is introduced into a water bath after passing through the air; the prepared membrane-forming solution has the following formula (1) and (2): 5 ≦ LST ≦ 40 (1) LST ≦ T D ≦ LST + 40 (2) [ wherein, the phase separation temperature of the LST film forming dope (℃), T _D is the film-forming stock solution temperature (℃) Represent. Is satisfied, the temperature of the film forming stock solution is adjusted so that the film forming stock solution is extruded from the double annular nozzle.
The relationship of the above equation (2) is satisfied up to a minute before. [However, S satisfies the relationship of 0 <S ≦ 1440.] And then until extrusion, LST-20 ≦ T _D <LST (3) (where LST and T _D are each as defined above), and form a film. was extruded stock solution, dual annular temperature of the air passing the extruded hollow fiber membrane from the nozzle following formula _{(4): T a ≦ LST} (4) [ wherein, T _a is a double annular nozzle Indicates the temperature (° C.) of the air passing through the extruded hollow fiber membrane, and LST is as defined above. ], And a method for producing a hollow fiber membrane. 5. A film-forming stock solution that is transparent and uniform at a high temperature but undergoes phase separation when the temperature is lowered, and extruding the film-forming stock solution while injecting a hollow forming agent inside a double annular nozzle,
A method for producing a hollow fiber membrane, in which a hollow fiber membrane extruded from the double annular nozzle is introduced into a water bath after passing through the air, wherein the prepared membrane-forming stock solution has the following formula (1) and (2): 5 ≦ LST ≦ 40 (1) LST ≦ T D ≦ LST + 40 (2) [ wherein, the phase separation temperature of the LST film forming dope (℃), T _D is the film-forming stock solution temperature (℃) Represent. Is satisfied, and the temperature of the film forming stock solution satisfies the relationship of the above formula (2) until the film forming stock solution is extruded from the double annular nozzle. after extrusion, the film-forming solution was extruded to receive the fold of the draft, the temperature is below the formula air passing the hollow fiber membrane extruded from the double annular nozzle _{(4): T a ≦ LST} (4) [ In the formula, T _A represents the temperature (° C.) of air passing through the hollow fiber membrane extruded from the double annular nozzle, and LST is as defined above. ], And a method for producing a hollow fiber membrane.