JPH0121986B2 - - Google Patents

Description

BACKGROUND OF THE INVENTION (Technical Field) The present invention relates to a method for manufacturing an artificial dialysis device used for hemodialysis. Specifically, the present invention relates to a method for manufacturing an artificial dialysis device using regenerated cellulose hollow fibers, which is used for hemodialysis and has high dialysis ability and low water removal ability. (Prior art) Artificial dialysis machines used for hemodialysis of patients with renal failure, poisonous substance poisoning, etc.
Toxic metabolites or poisonous substances such as uric acid and creatinine are transferred from the blood through the dialysis membrane of the artificial dialysis machine and into the dialysate based on the difference in concentration. One of the important functions of an artificial dialysis machine is to remove the parts. Conventionally, known dialysis membranes incorporated into such artificial dialysis equipment include cellulose-based materials such as regenerated cellulose and cellulose acetate, polysulfone, polyacrylonitrile, and polymethyl methacrylate, but currently there are no membranes that are in practical use. are primarily regenerated cellulose membranes, especially regenerated cellulose membranes from cuprammoniac cellulose.
Also, depending on the structure, artificial dialysis machines are hollow fiber type,
They can be broadly classified into coil type and flat membrane type, but hollow fiber type is currently most widely used because it is compact and can exhibit high dialysis performance. Now, such artificial dialysis equipment needs to be selected with appropriate water removal and dialysis performance depending on the patient's symptoms.For example, for patients who are initially introduced to artificial dialysis, An artificial dialysis device with low water removal capacity is appropriate. This artificial dialysis device with low water removal capacity is made by increasing the membrane thickness of the regenerated cellulose hollow fibers used conventionally.
Alternatively, it could be obtained by adjusting the amount of glycerin included during plasticization, adjusting the Normanization concentration, or changing the drying conditions in the manufacturing process of regenerated cellulose hollow fibers. However, controlling the amount of water removed by such a method is unstable, and furthermore, in order to spin hollow fibers with various performances, multiple production lines are required, which is very inconvenient. It was reasonable. OBJECTS OF THE INVENTION Therefore, an object of the present invention is to provide a novel method for manufacturing an artificial dialysis device used for hemodialysis. Another object of the present invention is to provide a method for manufacturing an artificial dialysis device used for hemodialysis, which uses regenerated cellulose hollow fibers with high dialysis and high water removal ability to reduce water removal ability while maintaining high dialysis ability. do. A further object of the present invention is to provide a method for manufacturing an artificial dialysis device suitable for patients who are initially introduced to artificial dialysis in hemodialysis. These purposes are achieved by loading a regenerated cellulose hollow fiber bundle into a cylindrical body, fixing both ends of the bundle to the cylindrical body, and then applying 60 to
This is achieved by a method for manufacturing a dry type artificial dialysis device used for hemodialysis, which is characterized by contacting with hot air at 150°C for 10 to 120 seconds. The present invention further provides a method for manufacturing a dry type artificial dialysis device, wherein the hot air contact is performed by passing hot air through the hollow fibers. The present invention also provides a method for manufacturing a dry type artificial dialysis device, wherein the hot air contact is performed by passing hot air through the outside of the hollow fiber. The present invention further provides a method for producing a dry type artificial dialysis device in which the regenerated cellulose hollow fibers are obtained from a cuprammonium cellulose spinning dope. DETAILED DESCRIPTION OF THE INVENTION Hereinafter, the present invention will be described in detail based on the drawings. FIG. 1 is a diagram showing a hot air treatment process in an embodiment of the method for manufacturing an artificial dialysis apparatus of the present invention. As shown in FIG. 1, the method for manufacturing an artificial dialysis apparatus of the present invention involves loading a regenerated cellulose hollow fiber bundle 1 into a cylindrical body 2 of an artificial dialysis apparatus, and fixing both ends of the assembled artificial dialysis apparatus. A circuit tube 7 connected to an air supply source 6 via an air heating device such as a heater 5 is connected to one blood port 4 or 10 of the device 3, and the air pumped from the air supply source 6 is connected to the blood port 4 or 10 of the device 3. It is heated to 60 to 150°C, preferably 100 to 140°C with a heater 5, and is sent into the artificial dialysis machine 3 through the blood port 4 or any dialysate port, and is transferred to the regenerated cellulose hollow fibers of the artificial dialysis machine 3. It is characterized by passing the hot air through it. However, at the stage where the regenerated cellulose hollow fiber bundle 1 is fixed at both ends, a suitable gripper connected to the circuit tube 7 is attached to either end, and after hot air treatment is performed, the artificial dialysis machine is attached. It is also possible to assemble. The regenerated cellulose hollow fibers of the artificial dialysis device 3 used in the present invention may be of any type as long as they have a high dialysis ability, but preferably are regenerated cellulose hollow fibers obtained from copper ammonia cellulose, such as copper ammonia cellulose. A spinning solution prepared by mixing a solution with a permeation performance controlling agent as necessary and making a coordination bond is discharged from an annular spinning hole, and at the same time a non-coagulable liquid is introduced and filled into the center of the interior, and then a non-coagulable liquid is introduced into the coagulable liquid. is passed through to coagulate and regenerate,
The hollow fiber thus obtained is washed, treated with glycerin if necessary, and then dried by an appropriate method.
Moreover, the regenerated cellulose hollow fiber has a film thickness of 5 to
It is about 30 μm, preferably about 10 to 25 μm. After such regenerated cellulose hollow fibers are cut to a predetermined length, they are bundled to achieve the required membrane area and loaded into the cylindrical body 2 of an artificial dialysis device. The regenerated cellulose hollow fiber bundle 1 is fixed to the cylindrical body 2 in accordance with a conventional method. For example, both ends of the regenerated cellulose hollow fiber bundle 1 are fixed to the cylindrical body 2 with a potting agent 8, 9 such as polyurethane. This is done by sealing both ends together. Headers 11 and 12 each having an inlet port 4 or an outlet port 10 for blood are brought into contact with both ends of the cylindrical body 2, and caps 13 and 14 connect the headers 11 and 12 to the cylindrical body 2, respectively. It is fixed. Note that an inlet port 15 and an outlet port 16 for dialysate are provided at both ends of the cylindrical body 2, respectively. After assembling the artificial dialysis device 3 in this way,
Blood inflow port 4 (or discharge port 10) of the artificial dialysis device 3 or dialysate inflow port 1
5 (or outlet port 16) is connected to a circuit tube 7 which is connected to an air supply source 6 via an air heating device such as a heater 5 on the way. In this state, the air supply source 6 and heater 5 are operated, and the circuit tube 7 is connected to the blood port 4 of the artificial dialysis machine 3.
blows hot air into the The hot air has a temperature of 60 to 150°C, more preferably 100 to 140°C. That is,
When the temperature of the hot air is below 60℃, there is virtually no effect on reducing the water removal ability due to hot air treatment.On the other hand, the higher the temperature of the hot air, the more the effect of reducing the water removal ability of the dialysis machine is seen. This is because if the temperature exceeds .degree. C., there is a risk of deterioration such as shrinkage of the hollow fibers, decrease in mechanical strength, and non-uniformity of the film thickness. Considering the deterioration of regenerated cellulose hollow fibers due to heat, the optimum temperature is 100 to 140°C. The suitable time for this hot air treatment is 10 to 120 seconds, preferably 30 to 60 seconds, and the blowing pressure of the hot air against the hollow fibers is
It is 0.5-2.0Kg/ ^cm2 , preferably 1.0-1.5Kg/ ^cm2 .
The hot air entering from the blood port 4 passes through the inside of each regenerated cellulose hollow fiber, and then flows out of the artificial dialysis apparatus 3 from the other blood port 10 and dialysate ports 15 and 16. Further, the hot air treatment may be performed before attaching the headers 11 and 12 to the artificial dialysis machine. In this case, a connector (not shown) may be provided at the end of the circuit tube 7 to be attached to the end of the cylindrical body 2 in a substantially airtight manner. Surprisingly, it has become clear that by subjecting the regenerated cellulose hollow fibers to such a simple hot air treatment, the water removal ability can be reduced without affecting the dialysis ability of the hollow fibers in any way. Ta.
Although the exact reason for this is not known, the hollow fibers are heated to near or above the highest temperature in the manufacturing history after the shape of the hollow fibers is almost determined by the hot air treatment (after solidification in the case of regenerated cellulose). This seems to be due to a change in the membrane structure. The artificial dialysis apparatus that has been assembled and subjected to hot air treatment in the manner described above is then sterilized, for example, by ethylene oxide gas sterilization, and provided as a dry type artificial dialysis apparatus. In the above description, the hot air was mainly brought into contact with the inside of the hollow fiber, but the present invention is not limited to this, and the hot air may be introduced from any dialysate port and brought into contact with the outside of the hollow fiber. In view of the construction of the dialysis device, it is considered more reliable to introduce the hot air into each hollow fiber through the blood port. Next, the present invention will be explained in more detail with reference to Examples. Example 1 An artificial dialysis device with an effective membrane area of about 1.0 m ² was assembled using about 6,800 copper ammonia cellulose hollow fibers with an inner diameter of about 200 μm, a membrane thickness of 12 μm, and an effective length of 235 mm. From the blood port on one side of the semi-finished product of this artificial dialysis machine.
After passing hot air at 140°C for 60 seconds, ethylene oxide gas sterilization was performed. In order to investigate the performance of the obtained artificial dialysis device, water removal ability, urea, creatinine and vitamin _B12 removal ability, and inulin permeability were measured. The results are shown in Table 1. In addition, in order to measure the ultrafiltration rate (UFR) in a water system as an indicator of the degree of water removal ability,
Under conditions of transmembrane pressure difference TMP (Note 1) 100 mmHg, city water is circulated to the blood side of the artificial dialysis machine at a flow rate of 200 ml/min at a temperature of 37°C, and the amount of water drained in 15 minutes is measured using a measuring cylinder. Then, the ultimate overspeed (UFR) was measured using the following formula. UFR (ml/mmHg・hr・^m2 =measured value (ml)/pressure (mmHg)
・Time (hr)・Area (m ² ) (Note 1: (Blood inlet side pressure Pi + blood outlet side pressure
Po)/2=100mmHg) Regarding the ability to remove urea, creatinine, and vitamin B12, an aqueous solution containing 2mg/dl of each component was added to the blood side of an artificial dialysis machine at a flow rate of 200ml/dl at 37°C.
On the other hand, on the dialysate side, city water at 37°C was flowed at a flow rate of 500 ml/min, and the pressure difference on the blood side at this time was set to 0 to maintain a state without water removal. The inlet side solution and outlet side solution were sampled, and the clearance calculated from the difference in concentration of each component was used as an index. Clearance (ml/min) = Inlet side concentration (mg/dl) - Outlet side concentration (mg/dl) / Inlet side concentration (mg/dl) x 200 (ml)
/min) Regarding inulin removal ability, 0.01M phosphate buffer solution (PH6.8) containing 20mg/dl inulin was
Warm to 200 °C and apply a flow rate to the blood side of the dialysis machine.
It was circulated at a rate of ml/min, the ultrafluid and the inlet side solution were sampled at TMP 200 mmHg, and the transmittance determined from the concentration ratio was used as an index. Transmittance (%) = Ultrafluid concentration (mg/dl) / Inlet side solution concentration (mg/dl) x 100 Example 2 A semi-finished artificial dialysis device assembled in the same manner as in Example 1 was connected to the blood port on one side. After performing hot air treatment by passing hot air at 125°C for 60 seconds, ethylene oxide gas sterilization was performed. The performance of the obtained artificial dialysis device was measured in terms of water removal ability, urea, creatinine and vitamin _B12 removal ability, and inulin permeability. The results are shown in Table 1. Example 3 The procedure of Example 1 was repeated except that hot air was introduced through the dialysate port on one side. Comparative Example 1 A semi-finished product of an artificial dialysis device assembled in the same manner as in Example 1 was sterilized with ethylene oxide gas without hot air treatment to obtain a product. The water removal ability, urea, creatinine and vitamin B ₁₂ removal ability, and inulin permeability of the obtained artificial dialysis device were measured and compared with Examples. The results are shown in Table 1. Comparative Example 2 A product was obtained in the same manner as in Example 1 except that the temperature of the hot air was 50°C. The water removal ability, urea, creatinine and vitamin B ₁₂ removal ability, and inulin permeability of the obtained artificial dialysis device were measured and compared with Examples. The results are shown in Table 1. Comparative Example 3 When hot air treatment was carried out in the same manner as in Example 1 except that the temperature of the hot air was 170°C, rapid shrinkage occurred in the hollow fibers, which caused the partition wall portion that supported the hollow fiber bundle at both ends to It was pulled inward and deformed, with its center caved in, making it unusable as an artificial dialysis device.

[Table] As is clear from the results shown in Table 1, the ultrafiltration rates of Examples 1 to 3 according to the present invention were clearly higher than that of Comparative Example 1, which was not subjected to hot air treatment. has decreased, resulting in lower water removal ability. On the other hand, in terms of dialysis performance, although a decrease was observed in the permeability of inulin with medium and high molecular weight, the clearance of other substances with low to low-medium molecular weight was unchanged from that of the comparative example, and the dialysis performance as an artificial dialysis device was substantially reduced. It was determined that no decrease was observed. Specific Effects of the Invention As described above, the present invention inserts a bundle of regenerated cellulose hollow fibers into a cylindrical body, fixes both ends of the bundle to the cylindrical body, and then inserts a bundle of regenerated cellulose hollow fibers into the regenerated cellulose hollow fibers. Since this is a manufacturing method for a dry type artificial dialysis device used for hemodialysis, which is characterized by contact with hot air at 150°C for 10 to 120 seconds, in the manufacturing process of regenerated cellulose hollow fibers, the amount of glycerin included during plasticization is By adjusting the amount, adjusting the Normanization concentration, or changing the drying conditions,
It is possible to control the water removal capacity more stably and with an extremely simple operation compared to controlling the water removal capacity, and it has almost no effect on the dialysis capacity, so it is recommended for the initial introduction of artificial dialysis. It is possible to provide a dry type artificial dialysis device with a relatively low water removal capacity required by dialysis patients such as patients. Furthermore, according to the manufacturing method of the present invention, after assembling the artificial dialysis device, the regenerated cellulose hollow fibers can be treated with hot air at 60 to 150°C for 10 to 120 seconds. The device can be manufactured using regenerated cellulose hollow fibers prepared under the same conditions, and there is no need to set up regenerated cellulose hollow fiber production lines for each water removal capacity. Furthermore, since the method of the present invention is a dry type, there is no step of filling water as in the wet type, so the manufacturing process is not only simple, but also the product is lightweight and easy to transport. Furthermore, there is no need to worry about freezing in cold regions, no special precautions are required for storage, and since dry sterilization is usually performed using ethylene oxide gas, etc., there is no need to choose a material for the housing in terms of heat resistance, pressure resistance, etc. There is. In addition, the resulting artificial dialysis device has a hot air treatment time of
It is 10 to 120 seconds, and is more excellent when the regenerated cellulose hollow fiber is obtained from a cuprammonium cellulose spinning dope.

[Brief explanation of drawings]

FIG. 1 is a diagram showing a hot air treatment process in an embodiment of the manufacturing method of the present invention. DESCRIPTION OF SYMBOLS 1... Regenerated cellulose hollow fiber bundle, 2... Cylindrical main body, 3... Artificial dialysis device, 4, 10... Blood port,
5...Heater, 6...Air supply source.

Claims (1)

[Claims] 1. After inserting a regenerated cellulose hollow fiber bundle into a cylindrical body and fixing both ends thereof to the cylindrical body, the regenerated cellulose hollow fibers are heated with hot air at 60 to 150°C for 10 to 10 minutes.
A method for manufacturing a dry type artificial dialysis device used for hemodialysis, which is characterized by contacting for 120 seconds. 2. The method for manufacturing an artificial dialysis device according to claim 1, wherein the contact with the hot air is performed by passing hot air through the hollow fibers. 3. The method of manufacturing an artificial dialysis device according to claim 1, wherein the contact with the hot air is performed by passing hot air through the outside of the hollow fiber. 4. The method for manufacturing an artificial dialysis device according to any one of claims 1 to 3, wherein the regenerated cellulose hollow fibers are obtained from a copper ammonia cellulose spinning dope.