JPS6132041B2 - - 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 method for producing a novel hollow fiber 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. 40168/1989), (2) ) Hollow artificial fiber body made of copper ammonia regenerated cellulose, in which the sectional structure has a denser porous structure in which the component parts near the outer surface are closer to the inner surface and the middle part (Special Publication No. 1363 of 1983) , (3) Electron microscopic observation of a cuprammonium regenerated cellulose tube having a hollow core when wet shows that the entire cross section and longitudinal section are substantially homogeneous and dense porous structures with microscopic gaps of at most 200 Å or less. There is also a hollow fiber for dialysis made of cuprammonium regenerated cellulose (Japanese Patent Application Laid-open No. 134920/1983), which has a skinless and smooth surface on both the inner and outer surfaces. Therefore, all of these hollow fibers extrude the copper ammonia cererose spinning stock solution into the air from the annular spinning hole and let it fall under their own weight, and at that time, the internal center of the spinning stock solution that is spun linearly. It is manufactured by introducing and filling a non-coagulable material into the spinning dope and discharging it, and then sufficiently stretching it by its own gravity and then immersing it in a dilute sulfuric acid solution to perform 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 cannot be bundled together to form a dialysis device. When inserting it into a tubular body and sealing both ends thereof with resin together with both ends of the main body, it is extremely difficult to uniformly distribute and arrange it in the sealed part because of its 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, causing the Only a portion of the dialysate flows through the bundled hollow fiber portion where the dialysate should flow 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.
It ended up being expensive and had the drawbacks of poor dialysis performance.

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 resulting hollow fibers all have skins on their outer surfaces to varying degrees depending on the manufacturing method, so it is impossible to obtain a hollow fiber that is homogeneous on both the inner and outer surfaces and inside. 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 eliminate the various drawbacks of the conventional products as described above. The spinning stock solution is directly extruded from the annular spinning hole into the non-coagulable liquid of the two-layer solution with the lower layer filled with After introducing and filling a coagulating liquid and adjusting the specific gravity of the linear spinning stock solution extruded from the spinning hole to be larger than the specific gravity of the non-coagulating liquid and smaller than the specific gravity of the coagulating liquid, and then discharging it,
It can be produced by running the liquid along the interface between the non-coagulable liquid and the coagulable liquid to perform solidification and regeneration.

Next, the present invention will be explained in more detail with reference to the drawings. That is, the hollow fiber according to the present invention is manufactured by the following method. That is,
As shown in FIG. 1, a bath 10 is provided with a coagulating liquid 11 having a higher specific gravity than the copper ammonia cellulose spinning dope as a lower layer and with respect to the spinning dope, and a coagulating liquid 11 containing the copper ammonia cellulose spinning dope and the coagulating liquid as an upper layer. A bath solution consisting of two layers is formed by supplying a non-coagulable liquid 12 having a specific gravity smaller than that of the spinning stock solution. A cuprammonium cellulose-based spinning stock solution is directly extruded into the non-coagulable liquid in the upper layer through a circular spinning hole (not shown) of the spinneret device 13, and at this time, the internal central part of the spinning stock solution extruded in a circular shape is A non-coagulable liquid for the spinning stock solution is introduced and filled into the spinning dope and discharged. The linear spinning stock solution 14 extruded from the annular spinning hole, while containing the non-coagulable liquid inside, advances downward through the upper layer of the non-coagulable liquid 12 without coagulating at all. In this case, while the linear spinning dope 14 receives the buoyancy of the non-coagulable liquid,
Since the liquid itself has a higher specific gravity than the non-coagulable liquid 12, it settles. Therefore, since the coagulable liquid 11 in the lower layer has a higher specific gravity than the linear spinning dope 14, the linear spinning dope 14 has a density of, for example, 20~ Proceeding at a linear speed of 50 m/min, preferably 50 to 80 m/min, the solidifying liquid 11
After sufficiently passing through the coagulable liquid 11 by a deflection rod 16 provided therein, it is pulled up from the roll 17 and sent to the next process.

Therefore, the linear spinning dope 14 has the above-mentioned interface 15
As shown in FIG.
Soak in 2. Therefore, the portion 3 that is in contact with the coagulable liquid 11 is quickly solidified from the outer surface, but the portion 14 that is in contact with the non-coagulable liquid 12 is not solidified, resulting in less volumetric shrinkage. However, in reality, this portion 4 does not come into contact with the coagulable liquid 11 at all, and the volume shrinkage due to solidification of the portion 3 that is in contact with the coagulable liquid 11 and the portion 4 that is in contact with the non-coagulable liquid 12 occur. Due to the difference in volumetric shrinkage, the linear spinning dope 14 twists to form a gentle spiral. Therefore, the portion 4 that is in contact with the non-coagulable liquid 12 also comes into contact with the coagulable liquid 11 and is finally completely coagulated.

In this way, the ratio of the length l to the entire circumference of the protrusion 4 and the ratio of the wall thickness d 3 of this portion 4 to the wall thickness d ₁ of the other portion ₃ are determined based on the coagulable liquid 11 and the non-coagulable liquid. Since it depends on the contact ratio of the linear spinning dope 14 to 12 and the advancing speed, any ratio can be obtained by appropriately selecting each specific gravity and advancing speed. 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. Further, if d ₃ /d ₁ is less than 1.3, the reinforcing effect and twisting will be insufficient, while if it exceeds 3 times, the dialysis performance will become uneven.

Note that if the linear spinning stock solution is to travel a sufficient distance, it is not necessarily necessary to use a diversion rod to immerse it in the coagulating liquid 11; instead, as shown in FIG. It may be pulled up directly with or without using it.

The hollow fibers obtained in this way are, for example,
As shown in the figure, in a hollow fiber 2 made of copper ammonia cellulose fiber having a hollow portion 1 continuously extending through the entire fiber length, the wall thickness d ₁ of the wall portion 3 is 1 to 0 μm over the entire fiber length. , preferably 3~
5 μm, and has an outer diameter d ₂ of 50 to 1000 μm, preferably 200 to 700 μm, and further 10 to 40%, preferably 20 to 35% of the total circumference.
The protrusion portion 4 is formed to have a thickness d ₃ that is 1.3 to 3 times, preferably 1.5 to 2.5 times, the wall thickness d ₁ . That is, the wall 3 having a wall thickness d ₁ has a substantially uniform thickness, while the protrusion 4 having a wall thickness d ₃ has a substantially uniform thickness.
It serves as a reinforcing structure for Therefore, the hollow fibers 2 have a slightly undulating and slightly spiral shape.

Various types of cellulose can be used, but one example is a cellulose with an average degree of polymerization of 500 to 500.
2500 is 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 cuprammonium cellulose solution may further be mixed with a permeation performance controlling agent for coordination bonding.

As the permeation performance controlling agent, for example, it contains 10 to 70 equivalent %, preferably 15 to 50 equivalent % of carboxyl groups in the constituent monomer positions, and has a number average molecular weight of 500 to 500.
200,000, preferably from 1,000 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. Therefore, as copolymerizable monomers, alkyl acrylates such as methyl acrylate, ethyl acrylate, isopropyl acrylate, butyl acrylate, hexyl acrylate, lauryl acrylate, alkyl methacrylates such as methyl methacrylate, ethyl methacrylate, butyl methacrylate, acrylamide, methacrylate, etc. Amide,
Examples include acrylonitrile, methacrylonitrile, hydroxyalkyl acrylate (or methacrylate), dialkylaminoacrylate (or methacrylate), vinyl acetate, styrene, vinyl chloride, etc., and alkyl acrylate and alkyl methacrylate are 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
Usually 1 to 40 parts by weight, preferably 2 to 30 parts by weight, most preferably 3 parts by weight, per 100 parts by weight of cellulose.
~15 parts by weight are used. For example, this permeability control agent is mixed and dissolved in an ammonia cellulose solution, and the temperature is 8 to 30°C, preferably 14 to 25°C.
A spinning stock solution is obtained by stirring for 120 minutes, preferably 60 to 100 minutes, to coordinate the copper ammonia 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 coagulating liquid for copper ammonia cellulose is
Its specific gravity is higher than the bulk specific gravity of the linear spinning dope, usually 1.03 to 1.31, preferably 1.05 to 1.31.
It is 1.18. To give an example, for example, a concentration of 5 to 40
%, preferably 8-25% sulfuric acid aqueous solution, concentration 5-25%
50%, preferably 10-30% nitric acid aqueous solution, concentration 6
-47%, preferably 9-30% phosphoric acid, etc.

The non-coagulable liquid for cuprammonium cellulose used as the upper layer has a specific gravity smaller than the bulk specific gravity of the linear spinning dope and is immiscible with the coagulable liquid, and its specific gravity is usually less than 0.71, preferably is less than 0.69. For example, n-hexane, n-heptane, n-
Examples include octane, n-decane, n-dodecane, liquid paraffin, light oil, kerosene, benzene, toluene, xylene, styrene, perchlorethylene, trichlorethylene, etc. Furthermore, the selection of the non-coagulable liquid to be spun into the linear spinning dope 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 fiber passes through the membrane and suddenly exits to the outside when the hollow fiber is dried, the pressure inside the hollow becomes reduced, causing hollow collapse or unevenness on the inner wall. The non-coagulating liquid used is selected to have low permeability during drying. Suitable non-coagulating liquids include those described above.

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 15% by weight. % concentration of glycerin aqueous solution to remove remaining copper, cupric sulfate, copper hydrogen sulfate, medium-low molecular weight cellulose, etc., and then dried and wound to form the desired hollow. get thread.

Examples of strong alkalis include sodium hydroxide, potassium hydroxide, lithium hydroxide, ammonium hydroxide, etc., with a concentration of 0.1 to 20%, preferably 1 to 15%.
% aqueous solution.

As described above, the method for producing hollow fibers according to the present invention comprises filling the upper layer with a non-coagulable liquid relative to the copper ammonia cellulose-based spinning dope, and further filling the lower layer with a coagulating liquid having a higher specific gravity than the non-coagulating liquid. The spinning dope is directly extruded from the annular spinning hole into the non-coagulable liquid of the two-layer solution, and the non-coagulable liquid corresponding to the spinning dope is introduced and filled 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 non-coagulable liquid and smaller than the specific gravity of the coagulable liquid and discharge it, the non-coagulable liquid and the coagulable liquid are Since this is carried out by coagulation and regeneration by running along the interface with the liquid, it not only generates the above-mentioned protrusions, but also causes a difference in shrinkage due to the difference in solidification rate due to the formation of the protrusions. , which causes twisting or curling, producing the effect described above. In addition, since the spinning stock solution is not spun into a gaseous atmosphere such as air but directly into a non-coagulable liquid, there is no volatilization of ammonia when passing through a gaseous atmosphere as in conventional methods. Therefore, the hollow fibers obtained are completely uniform on both the inside and outside surfaces and inside.

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 cupric ammonia aqueous solution was prepared by suspending 514 ml 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 a 10% aqueous sodium hydroxide solution was added to prepare an aqueous cuprammonium cellulose solution (specific gravity 1.08), which was used as a spinning stock solution.

On the other hand, using a device as shown in Figure 2, 20% nitric acid (specific gravity
1.12) and n-heptane (specific gravity
0.68). The spinning dope was introduced into a spinneret device 13 equipped with an annular spinning hole, and directly discharged from the spinning hole into the upper layer of n-heptane under a nitrogen pressure of 2 kg/cm ² . The diameter of the spinning hole is 3.8mm,
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 a non-coagulable liquid introduction tube attached to the spinneret device, 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. Then,
Discharge stock solution (linear spinning stock solution containing non-coagulable liquid)
14 (specific gravity 1.025) was precipitated in n-heptane,
Furthermore, the interface between n-heptane and sulfuric acid aqueous solution was run. At this time, the temperature of both liquids was 20℃, the running linear speed was 80m/min, and the running distance was 2.
It was hot. After taking it out of the bath, it was decoppered in a 20% sulfuric acid bath (bath length approximately 4 m) and then wound onto a winding case. The yarn wound into a skein is placed in a tank, filled with hot water, heated to 30℃, and then heated to 10℃.
I washed the time. After further alkaline washing and subsequent glycerin treatment with an 8% glycerin aqueous solution, the resulting yarn was passed through a tunnel drying oven (length 5 mm) maintained at 120°C ± 10°C at a running speed of 10 m/min. It was run and dried to obtain a hollow fiber.

As shown in Figure 5, the hollow fiber thus obtained has an outer diameter of 200 μm, a wall thickness of 12 μm, and approximately 30% of the entire circumference has protrusions that are approximately 1.6 times the wall thickness. It had a slight curling property, and was uniform and skinless over both the inner and outer surfaces and the inside. Moreover, its tensile strength was 10 Kg/mm ² .

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 5200], the results shown in Table 1 were obtained. Note that the dialysate at this time was water, and its flow rate (Q _D ) was 500 ml/min. Further, the flow rate (Q _B ) of the blood substitute containing indicator substances such as inulin, vitamin B ₁₂ , creatine, urea, and PO ₄ ^-- is 200 ml/min. UFR is 4.6ml/mm
I had Hg/hr.

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

Example 2 155 g of an ammonium salt of an acrylic acid-methyl methacrylate copolymer having a number average molecular weight of about 50,000 and having 17.8 equivalent % of carboxyl groups was added to the spinning stock solution of Example 1, and the mixture was heated at a temperature of about 25° C. while cooling.
The mixture was reacted for 60 minutes with stirring, and then thermally formed 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 a 5% aqueous sulfuric acid solution at a bath length of 10 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 20 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.

As shown in Figure 6, the hollow fiber thus obtained has an outer diameter of 200 μm, a wall thickness of 11 μm, and approximately 25% of the entire circumference has protrusions that are approximately 1.4 times the wall thickness. It had a slight curling property, and was uniform and skinless over the inner and outer surfaces and inside. Also, its tensile strength
It was 9.5Kg/ ^mm2 .

A dialysance test was conducted on the hollow fiber thus obtained in the same manner as in Example 1, and good results were obtained. Also,
In a dialysis device manufactured by inserting this bundle of hollow fibers into a cylindrical body, the hollow fibers were uniformly dispersed within the body, and 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 invention, Fig. 3 is a schematic diagram of another apparatus, and Fig. 4 FIG. 5 is a partial perspective view showing the schematic structure of a hollow fiber obtained by the method of the present invention;
The figure is a micrograph of hollow fibers obtained by the method of the present invention. DESCRIPTION OF SYMBOLS 1... Hollow part, 2... Hollow fiber, 3... Wall part, 4... Projection part, 10... Bathtub, 11... Coagulating liquid, 12... Non-coagulating liquid, 13... Spinneret device, 14... Linear spinning dope .

Claims (1)

[Scope of Claims] 1. The non-coagulation of a bath liquid consisting of two layers, the upper layer being filled with a non-coagulating liquid for the copper ammonia cellulose-based spinning dope, and the lower layer being filled with a coagulating liquid having a higher specific gravity than the non-coagulating liquid. A line extruded from the spinning hole by directly extruding the spinning dope through the annular spinning hole, and introducing and filling a non-coagulable liquid with respect to the spinning dope into the center of the annularly extruded spinning dope. After adjusting the specific gravity of the shaped spinning stock solution to be larger than the specific gravity of the non-coagulable liquid and smaller than the specific gravity of the coagulable liquid and discharge it, the solution is made to travel along the interface between the non-coagulable liquid and the coagulable liquid. 1. A method for producing a hollow fiber for dialysis, characterized by performing coagulation and regeneration. 2. The method according to claim 1, wherein the spinning stock solution contains a permeation performance controlling agent.