JPS6132042B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for manufacturing hollow fibers. More specifically, the present invention relates to a new method for manufacturing hollow fibers for dialysis used in artificial kidney devices and the like.

In recent years, artificial kidney devices that utilize osmotic action, ultraviolet action, etc. have made remarkable progress and are widely used in the medical world. Therefore, in such an artificial kidney device, the extremely thin hollow fiber for dialysis is the most important component.

Typical hollow fibers for dialysis include: (1) total fiber length and circumference ranging from several μm to 60 μm;
Uniform wall thickness of m and outer diameter from 10 μm to several hundred μm
Hollow fibers made of copper ammonia cellulose fibers having a uniform perfect circular cross section and a hollow portion that extends continuously over the entire length of the stretched and oriented fibers (Japanese Patent Publication No. 40168/1983), (2) ) Hollow artificial fibrous body made of copper ammonia recycled cellulose in which the cross-sectional structure has a denser porous structure in which the constituent parts near the outer surface are closer to the inner surface and the intermediate parts (Special Publication No. 1363 of 1983) , (3) Electron microscopic observation of a cuprammonium regenerated cellulose tubular body having a hollow core when wet shows a substantially homogeneous and minute porous structure with fine pores of at most 200 Å or less in the entire cross-sectional and longitudinal sections. There are hollow fibers for dialysis made of copper ammonia regenerated cellulose (Japanese Patent Application Laid-open No. 134920/1983), which is made of body and has a skinless and smooth surface on both the inner and outer surfaces. Therefore, in both of these hollow fibers, the cuprammonium cellulose spinning dope is extruded into the air through the annular spinning hole and allowed to fall under its own weight. It is produced by introducing and filling a non-coagulable liquid into the spinning stock solution and discharging it, then sufficiently stretching it by its own weight, and then immersing it in a dilute sulfuric acid solution for coagulation and regeneration.

To make a dialysis device such as an artificial kidney device using these hollow fibers, for example, after inserting the bundle of hollow fibers into a tubular body having an artificial tube and an outlet tube near both ends, This is done by sealing both ends of the tubular body with a resin such as polyurethane, respectively, and
For example, it has a structure similar to a shell-and-tube type device in a heat exchanger.

However, all of the hollow fibers have a wall thickness of several μm to 60 μm and an outer diameter of 10 μm to several hundred μm, so they are not only insufficient in strength, but also have a straight shape, so they are bundled together for dialysis. When inserted into the tubular body of the device and sealed with resin at both ends of the body, it is extremely difficult to uniformly distribute and arrange them in the sealed portion because of their low bulk. Therefore, the hollow fibers are concentrated in a certain part of the tubular body, and the other part becomes a cavity. Therefore, during use, the dialysate primarily short-circuits through this cavity, and the dialysis fluid is originally Only a portion of the filtrate flows through the bundled hollow fiber portion where it should be distributed the most, resulting in a significantly lower dialysis effect. Furthermore, even if such linear hollow fibers could be dispersed and arranged in a somewhat uniform manner within the tubular body, the dialysate flows linearly through the gaps along the hollow fibers, making it difficult for sufficient mixing to occur. There were flaws.

In order to eliminate these drawbacks, the linear hollow fibers are twisted in advance to give them a curl, thereby making the hollow fibers bulky when bundled. A uniformly distributed arrangement of threads is being measured. However, this method requires extra steps such as a twisting step and a heat setting step, which complicates the manufacturing process of the dialysis device.
The drawback was that it ended up being expensive.

Furthermore, the hollow fibers are manufactured by extruding the copper ammonia cellulose spinning dope into a gaseous atmosphere such as air, allowing it to fall under its own weight, and then immersing it in a coagulation solution to coagulate and regenerate it. While falling through the atmosphere, ammonia separates to some extent and begins to solidify from the surface. Therefore, the obtained hollow fibers have a skin on the outer surface to varying degrees depending on the manufacturing method, so that both the inner and outer surfaces and the inside of the fiber are not homogeneous. For this reason, when such hollow fibers are used in a dialysis device, the pore diameters of the micropores generated on the inner surface and inside and outside surfaces are different, so the performance is inconsistent and it is difficult to obtain a good dialysis effect. There was a drawback.

The present invention was made in order to solve the above-mentioned drawbacks of the conventional method, and includes a coagulating liquid in the upper layer for the copper ammonia cellulose spinning dope, and a non-coagulating liquid having a higher specific gravity than the coagulating liquid. Directly extruding the spinning stock solution from the two layers filled in the lower layer into the non-coagulating liquid of the bath liquid through the annular prevention hole,
and introducing and filling a non-coagulating liquid with respect to the spinning dope into the central part of the spinning dope extruded in an annular shape so that the specific gravity of the linear spinning dope extruded from the spinning hole is greater than the specific gravity of the non-coagulating liquid; Production of a hollow fiber for dialysis, characterized in that the specific gravity is adjusted to be lower than that of the coagulable liquid and then discharged, and then run along the interface between the non-coagulable liquid and the coagulated holy liquid to perform coagulation regeneration. It's a method.

Next, the method of the present invention will be explained in detail with reference to the drawings. That is, as shown in FIG. 1, in a bathtub 1, a lower tank contains a non-coagulating liquid 2 which has a higher specific gravity than the copper ammonia cellulose spinning dope and is relative to the spinning dope, and an upper layer contains a non-coagulating liquid 2 which is higher in specific gravity than the non-coagulating liquid. A bath liquid consisting of two layers is formed by supplying a coagulating liquid 3 having a small specific gravity and relative to the cuprammonium cellulose-based spinning dope. A cuprammonium cellulose-based spinning dope is directly extruded into this lower non-coagulable liquid through a conduit 4 through an annular spinning hole (not shown) of a spinneret device 5, and at this time, the interior of the annularly extruded spinning dope is A non-coagulating liquid for the spinning dope is introduced and filled into the center and discharged. The linear spinning dope 6 extruded from the annular spinning hole advances upward through the lower non-coagulable liquid 2 without coagulating at all while containing the non-coagulable liquid inside. in this case,
The linear spinning dope 6 rises while being affected by the buoyancy of the non-coagulable liquid. However, since the linear spinning dope 6 does not necessarily have a lower specific gravity than the coagulable liquid in the upper layer, the interface 7 between the non-coagulable liquid 2 and the coagulable liquid 3 is usually
At least one deflection bar 8 provided nearby prevents entry into the coagulable liquid 2, and the speed is e.g. 20 to 150 m/min, preferably 50 to
It is allowed to proceed at a linear speed of 100 m/min, and after passing sufficiently through the coagulating liquid 3 using a changing rod 9 provided as necessary, it is pulled up from a roll 10 and sent to the next step.

Therefore, while the linear spinning stock solution 6 passes through the interface 7, as shown in FIG. . Therefore, the portion 11 that is in contact with the coagulable liquid 3 is rapidly solidified from the outer surface, but the portion that is in contact with the non-coagulable liquid 2 is not coagulated, resulting in less volumetric contraction. However, in reality, this part does not come into contact with the coagulable liquid 3 at all, and the volume shrinkage due to coagulation of the part 11 in contact with the coagulable liquid 3 and the part in contact with the non-coagulable liquid 2 Due to the difference in volumetric contraction of 12, the linear spinning dope 6 twists to form a gentle spiral. Therefore, the portion 12 that is in contact with the non-coagulable liquid 2 also comes into contact with the coagulating liquid 3 and is finally completely coagulated.

As shown in FIG. 3, the hollow fibers obtained in this manner have hollow fibers 14 made of copper ammonia cellulose fibers having hollow portions 13 continuously extending through the entire fiber length. The wall thickness d ₁ of the part 11 is 8 to 30 μm, preferably 10 to 15
μm, and the outer diameter _d2 is 110 to 350 μm, preferably 150 to 250 μm, and furthermore, out of the entire circumference,
10-40%, preferably 20-35% of the portion l is 1.3-3 times the wall thickness d ₁ , preferably 2-35% of the portion l is 1.3-3 times the wall thickness d ₁ , preferably 1.5～
The protruding portion 12 is formed to have a thickness _d3 that is 2.5 times as large. That is, the wall portion having the wall thickness d ₁ has a substantially uniform thickness, while the protruding strip portion having the wall thickness d ₃ serves as a reinforcing structure for the wall portion. Therefore, the hollow fibers 14 have a slightly undulating and slightly spiral shape.

In this way, the ratio of the length l to the entire circumference of the protrusion 12 and the ratio of the wall thickness d ₃ of this portion 12 to the wall thickness d ₁ of the other portion 11 are determined based on the coagulable liquid 3 and the non-coagulable liquid. Since it depends on the contact ratio of the linear spinning stock solution 6 to 2 and the advancing speed, any ratio can be obtained by appropriately selecting the specific gravity and advancing speed of each. However, if the length l is less than 10% of the total circumference, the strength and twist will be insufficient, while if it exceeds 40%, the dialysis performance may become uneven. Furthermore, if d ₃ /d ₁ is less than 1.3, the reinforcing effect and twisting will be insufficient, while if it exceeds 3 times, dialysis performance will become uneven.

Various types of cellulose can be used, but one example is a cellulose with an average polymerization of 500 to 2500.
are preferably used. Thus, the cuprammonium cellulose solution is prepared by a conventional method.
For example, first, aqueous ammonia, a basic aqueous copper sulfate solution, and water are mixed to prepare an aqueous cupric ammonia solution, an antioxidant (e.g., sodium sulfite) is added to this, then raw cellulose is added and dissolved with stirring, and then An aqueous sodium hydroxide solution is added to completely dissolve undissolved cellulose to obtain a cuprammonium cellulose solution. This copper ammonia cellulose solution may further be mixed with a permeation performance controlling agent for coordination bonding.

As the permeation performance controlling agent, for example, an agent having a number average molecular weight of 500 to 500 and containing 10 to 70 equivalent %, preferably 15 to 50 equivalent % of carboxyl groups in the constituent monomer units is used.
200,000, preferably from 1000 to 100,000. There are various types of such polymers, but examples include copolymers of carboxyl group-containing unsaturated monomers such as acrylic acid and methacrylic acid with other copolymerizable monomers, and polyacrylonitrile. There are partial hydrolysis products. However,
As copolymerizable monomers, methyl acrylate,
Alkyl acrylates such as ethyl acrylate, isopropyl acrylate, butyl acrylate, hexyl acrylate, raur acrylate, methyl methacrylate, alkyl acrylates such as ethyl methacrylate, alkyl methacrylates such as methyl methacrylate, ethyl methacrylate, butyl methacrylate, acrylamide, methacrylamide, acrylonitrile,
Examples include methacrylonitrile, hydroxyal acrylate (or methacrylate), dialkylamino acrylate (or methacrylate), vinyl acetate, styrene, vinyl chloride, etc., with alkyl acrylate and alkyl methacrylate being particularly preferred. Therefore, the most preferred copolymers are acrylic acid-alkyl acrylate (or methacrylate) copolymers, methacrylic acid-alkyl acrylate (or methacrylate) copolymers, and partial hydrolysis products of polyalkyl acrylates (or methacrylates). It is. These permeability control agents are used generally in an amount of 1 to 40 parts by weight, preferably 2 to 30 parts by weight, and most preferably 3 to 15 parts by weight, per 100 parts by weight of cellulose. For example, this permeability control agent is mixed and dissolved in a cupric ammonia cellulose solution, and the temperature is preferably 8 to 30°C.
Preferably 60-100 for 20-120 minutes at a temperature of 14-25℃
A spinning stock solution is obtained by stirring for a minute to coordinately bond the cuprammonium cellulose.

Such spinning dope usually has a specific gravity of 1.05 to 1.15.
and preferably 1.06 to 1.10. However, as will be described later, the inside of the linear spinning dope extruded from the spinning hole is filled with a non-coagulable liquid, so the specific gravity is usually lower than that of the spinning dope, with a specific gravity of 1.00 to 1.00.
1.08, preferably 1.01 to 1.04.

The non-coagulable liquid for the cuprammonium cellulose used as the lower layer has a bulk specific gravity larger than that of the linear spinning dope (spinning dope containing a non-coagulable liquid), and is immiscible with the non-coagulable liquid. The specific gravity is higher than this, and the specific gravity is usually greater than 1.2. Preferably it is greater than 1.25. An example is fluorinated silicone oil (specific gravity 1.25-1.30). Furthermore, the selection of the non-coagulable liquid to be spun into the linear spinning stock solution greatly influences the maintenance of the hollow portion of the hollow fiber and the presence or absence of irregularities on the wall surface of the hollow fiber. That is, when the non-coagulable liquid filled in the hollow fibers passes through the membrane and suddenly exits the hollow fibers, the pressure inside the hollow fibers decreases, causing collapse of the hollow fibers or unevenness on the inner walls.
The non-coagulating liquid used is selected to have low permeability during drying. Examples of suitable non-coagulable liquids include n-hexane, n-
Heptane, n-octane, n-decane, n-dodecane, liquid paraffin, light oil, kerosene, benzene,
Examples include toluene, xylene, styrene, perchlorethylene, trichlorethylene, etc.

The coagulating liquid for copper ammonia cellulose is
Its specific gravity is lower than that of the non-coagulable liquid, and it is usually
It is 1.03 to 1.31, preferably 1.05 to 1.18. For example, a sulfuric acid aqueous solution with a concentration of 5 to 40%, preferably 8 to 25%, a nitric acid aqueous solution with a concentration of 5 to 40%, preferably 8 to 25%, a concentration of 6 to 47%,
Preferably 9 to 30% phosphoric acid is used.

The hollow fibers that have been coagulated and regenerated in this way are washed with water to remove the adhering coagulating liquid, and then, if necessary, subjected to decopper treatment to remove copper remaining in the hollow fibers. , then washed with water.
Copper removal treatment is usually carried out by immersion in a dilute sulfuric acid solution or nitric acid solution with a concentration of 3 to 30%. However,
When the spinning stock solution contains a permeation performance controlling agent as described above, the hollow fibers are immersed in a strong alkaline aqueous solution to remove the controlling agent, thereby forming fine particles corresponding to the molecular weight of the polymer used. Holes are formed in the tube wall of the hollow fiber.

The hollow fibers after washing with water or after removing the permeability control agent may be further treated with warm water at 5 to 100°C, preferably 50 to 80°C, or 1 to 10% by weight, preferably 2 to 5% by weight. % concentration glycerin solution and still remaining copper,
Cupric sulfate, copper hydrogen sulfate, medium-low molecular weight cellulose, etc. are removed, and the fiber is then dried and wound to obtain the desired hollow fiber.

Examples of strong alkalis include sodium hydroxide, potassium hydroxide, lithium hydroxide, ammonium hydroxide, etc., and the concentration is ~0.1-20%, preferably 1-20%.
Used as a 15% aqueous solution.

As described above, the method for manufacturing hollow fibers for dialysis according to the present invention involves filling the lower layer with a non-coagulable liquid relative to the cuprammonium cellulose-based spinning stock solution, and further filling the upper layer with a coagulating liquid having a higher specific gravity than the coagulating liquid. The spinning dope is directly extruded from the annular spinning hole into the coagulable liquid of the two-layer solution, and a non-coagulable liquid corresponding to the spinning dope is introduced into the center of the annularly extruded spinning dope. After adjusting the specific gravity of the linear spinning dope to be extruded from the spinning hole to be larger than the specific gravity of the coagulable liquid and greater than the specific gravity of the non-coagulable liquid and discharge it, Since it is coagulated and regenerated by running along the interface between a liquid and a coagulable liquid, it generates the above-mentioned protrusions, which not only increases mechanical strength but also reduces the amount of protrusions produced. Differences in solidification rates due to this cause shrinkage, which causes twisting or curling, resulting in the effects described above. In addition, since the spinning solution is directly spun into a non-coagulable liquid without being spun into a gaseous atmosphere such as air, there is no volatilization of ammonia when passing through a gaseous atmosphere, unlike in conventional methods. For this reason, the resulting hollow fibers are completely uniform on both the inner and outer surfaces and inside.

Furthermore, since the coagulable liquid is present in the upper layer, the problem of volatilization due to evaporation of non-coagulable liquid is eliminated.

Next, the present invention will be explained in more detail by giving Examples. In addition, in the following examples, all percentages are by weight unless otherwise specified.

Example 1 A copper ammonia aqueous solution was prepared by suspending 5148 g of a 28% ammonia aqueous solution and 864 g of basic copper sulfate in 1200 ml of water, and 2725 ml of a 10% sodium sulfite aqueous solution was added thereto. This solution has a degree of polymerization of approximately 1000.
1900 g of cotton linter pulp (±100) was added and dissolved with stirring, and then 1600 ml of 100% sodium hydroxide aqueous solution was added to prepare a cuprammonium cellulose aqueous solution (specific gravity 1.08), which was used as a spinning stock solution.

On the other hand, using a device as shown in Figure 1, 20% sulfuric acid (specific gravity 1.11) was added as a coagulating liquid to the upper layer of bathtub 1.
and silicone oil (specific gravity 1.27) as the lower layer
was supplied. The spinning dope was introduced into a spinneret device 5 equipped with an annular spinning hole, and directly discharged from the spinning hole into the silicone oil in the lower layer under a nitrogen pressure of 2 kg/cm ² . The diameter of the spinning hole was 3.8 mm, and the discharge rate of the spinning dope was 13.7 ml/min. On the other hand, isopropyl myristate (specific gravity: 0.854) was introduced from the non-coagulable liquid introduction tube 4 attached to the spinneret device, and was encapsulated in the spinning dope and discharged. The diameter of the introduction tube was 1.2 mm, and the discharge rate of isopropyl myristate was 4.22 ml/min. Next, discharge stock solution (linear spinning stock solution containing non-coagulable liquid) 6 (specific gravity
1.026) was raised in silicone oil and then run across the interface between silicone oil and aqueous sulfuric acid solution.
At this time, the temperature of both liquids was 20°C, the running linear speed was 80 m/min, and the running distance was 10 m. After taking it out of the bathtub, it was washed with water in a bath with a length of about 10 meters, and then wound up into a winding case. The yarn wound into a skein was placed in a tank, filled with warm water, heated to 30°C, and washed for 10 hours. The obtained yarn was dried by running at a running speed of 10 m/min in a tunnel type drying oven (length 5 m) maintained at 120° C.±10° C. to obtain a hollow fiber.

The hollow fiber thus obtained has an outer diameter of 210μ
m, wall thickness 11μm, approximately 20% of the entire circumference forms a protrusion with a thickness approximately 1.2 times the wall thickness, has a slight curling property, and has a ridge on both the inner and outer surfaces and the inside. It was skinless and homogeneous throughout.

Using the hollow fiber thus obtained (membrane area: 1.0 m ² ), an indicator substance with a known molecular weight [urea (BUN): molecular weight 60, phosphate ion: molecular weight 95,
Creatinine molecular weight 113, vitamin B ₁₂ : molecular weight
1355 and inulin (molecular weight 2500)], good results were obtained. Note that the dialysate at this time is water,
Its flow rate (Q _D ) is 500 ml/min. Also, inulin vitamin B ₁₂ , creatine, urea, PO ₄ ^--
The flow rate of the blood substitute (Q _B ) containing the indicator substance is 200
ml/min. UFR was 4.9 ml/mmHg·hr.

Furthermore, in a dialysis device manufactured by inserting this bundle of hollow fibers into a cylindrical body, the hollow system was uniformly dispersed within the body, and no short circuit was observed during the passage of the dialysate.

Example 2 An ammonia salt of an acrylic acid-methyl methacrylate copolymer having a number average molecular weight of approximately 50,000 and having 17.8 equivalent % of carboxyl groups was added to the spinning stock solution of Example 1.
60 at a temperature of about 25℃ while cooling by adding 155g.
The mixture was reacted for a minute with stirring and further aged to obtain a spinning stock solution.

The spinning stock solution thus obtained was prepared in Example 1.
After spinning and regenerating coagulation in the same manner as above, the obtained yarn was run in a copper removal bath filled with 5% sulfuric acid solution at a bath length of 20 m. After washing with water, the copolymer salt was removed by running it in an alkaline bath filled with 4% sodium hydroxide at a bath length of 10 m, followed by washing with water and winding. The processing speed at this time was 10 m/min. The thread wound around the skein was treated with hot water in the same manner as in Example 1, and then dried to obtain a hollow fiber.

The hollow fiber thus obtained has an outer diameter of 212μ
m, wall thickness 12 μm, approximately 23% of the entire circumference forms a protrusion with a thickness approximately 1.2 times the wall thickness, has a slight curling property, and has a ridge on both the inner and outer surfaces and the inside. It was skinless and homogeneous throughout. Further, its tensile strength was 10.3Kg/mm ² .

A dialysance test was conducted on the hollow fiber thus obtained in the same manner as in Example 1, and good results were obtained. In addition, in a dialysis device manufactured by inserting a bundle of hollow fibers into a cylindrical shape, the hollow fibers are uniformly dispersed within the main body,
Furthermore, no short circuit was observed during the passage of the dialysate.

[Brief explanation of the drawing]

FIG. 1 is a schematic diagram of an apparatus for carrying out the method of the present invention, FIG. 2 is a sectional view for explaining the principle of producing hollow fibers according to the present invention, and FIG. 3 is a diagram showing hollow fibers obtained by the method of the present invention. FIG. 2 is a partial perspective view showing a schematic structure of a thread. 1... Bathtub, 2... Non-coagulable liquid, 3... Coagulable liquid, 5
... Spinneret device, 6... Linear spinning dope.

Claims (1)

[Scope of Claims] 1. A bath liquid consisting of two layers, the upper layer being filled with a coagulating liquid for the copper ammonia cellulose-based spinning stock solution, and the lower layer being filled with a non-coagulating liquid having a higher specific gravity than the coagulating liquid. A non-coagulable liquid for the spinning dope is introduced and filled into the coagulable liquid into the center of the spinning dope that has been extruded in a circular shape, and the specific gravity of the linear spinning dope extruded from the spinning hole is determined as described above. The specific gravity is adjusted to be higher than that of the non-coagulable liquid and lower than that of the coagulable liquid, and then discharged, and then run along the interface between the non-coagulable liquid and the coagulable liquid to perform coagulation regeneration. A method for producing hollow fibers for dialysis. 2. The method according to claim 1, wherein the spinning stock solution contains a permeation performance controlling agent. .