JPH0751362A - Hemo-dialyzer - Google Patents

Abstract

PURPOSE:To provide a hemo-dialyzer using the hollow fiber membrane prepared from a material of dispersion mixture of cellulose triacetate and cellulose diacetate wherein the background functions, the percent ratio by weight of cellulose diacetate in material and the respective screening coefficients for albumin and myoglobin after a high-pressure steam sterilization, are maintained in the specific values. CONSTITUTION:A dialyzer for blood is produced which comprises a container having an inlet and outlet of blood, a hollow fiber unit in the container, wherein a hollow fiber is made of a uniformly admixed dispersion of cellulose triacetate and cellulose diacetate so that the content of cellulose diacetate is 1-50wt.%, the screening coefficients for albumin and myoglobin after high-pressure steam cooking at 121 deg.C for 20 minutes are of not less than 0.1 and not more than 0.1 respectively. These background functions show none of the lowering of efficiency in the cooking process and the low dispersion in quality to give sufficiently sterilized product.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sterilized hemodialyzer represented by an artificial kidney.

[0002]

2. Description of the Related Art Artificial organs have been remarkably developed as a substitute or complement for the functions of human organs, and artificial kidneys have been widely spread. The artificial kidney substitutes the function of living kidney by ultrafiltration of excess water in blood and removal of waste products. This artificial kidney must be sterilized in the final step, but as a conventional sterilization method, there has been a method using formalin or ethylene oxide gas. However, since these methods use a sterilizing agent, a small amount of residual amount poses a safety problem.

As a sterilization method that does not use a sterilizing agent, there is a method using radiation. Since the artificial kidney is irradiated with γ-rays of 0.5 to 5 megarads, there is no concern about residual toxicity, but there is a problem that the components of the artificial kidney, especially the dialysis membrane, are significantly deteriorated and an eluate is generated. Further, there is a drawback that a large-scale device is required.

In contrast to these methods, there is high-pressure steam sterilization as heat sterilization. This is usually performed in a saturated steam atmosphere at 115 to 121 ° C. for about 20 to 30 minutes,
It has the advantage of no residual toxicity. However, it is necessary to pay sufficient attention to the heat resistance of the materials that make up the blood purification membrane and the heat inferiority of the semipermeable membrane. It has been put to practical use only in a limited combination of materials. At present, there are cellulose diacetate membranes and cellulose triacetate membranes as materials for semipermeable membranes used in blood purification membranes typified by artificial kidneys. Conventionally, these cellulose acetate membranes have the basic performance when sterilized by high pressure steam. I couldn't keep up.

[0005]

In order to solve these problems, the inventors of the present invention have made extensive studies and as a result, as a result of using a hollow fiber membrane composed of a mixture of cellulose triacetate and cellulose diacetate, high pressure steam is obtained. They found that the basic performance was maintained even after sterilization, and completed the present invention.

[0006]

That is, the present invention comprises a material in which cellulose triacetate and cellulose diacetate are uniformly mixed and dispersed, and the weight percentage of cellulose diacetate is in the range of 1 to 50% by weight. ,
Hemodialysis in which a hollow fiber membrane having a sieving coefficient of albumin of 0.1 or less and a sieving coefficient of myoglobin after high-pressure steam treatment at 121 ° C. for 20 minutes is 0.1 or more is housed in a container having an inlet and an outlet. It is related to vessels.

The cellulose diacetate used in the present invention has an acetylation degree of 52 to 58% by weight, and cellulose triacetate has an acetylation degree of 60 to 60% by weight.
Means in the range of 62% by weight. The degree of acetylation here is represented by the following formula. Acetification degree (%) = (acetic acid equivalent mass of acetyl group / total mass) x 100

The high-pressure steam sterilizable hollow fiber membrane according to the present invention is manufactured, for example, as follows. That is, the total concentration of cellulose triacetate and cellulose diacetate in the spinning dope is 10% by weight or more, and an aprotic polar solvent having a boiling point of 150 ° C. or more and a spinning dope prepared by using a non-solvent are prepared in a double tube. Discharge from the nozzle.
During this discharge, the discharge temperature (T1) and the coagulation bath temperature (T
It is important to control the relationship of 2) to 0 <T1-T2 ≦ 100 (° C.). The coagulation bath uses an aqueous solution of the above solvent and non-solvent. As the aprotic polar solvent, N-methylpyrrolidone, dimethylformamide, dimethylacetamide, dimethylsulfoxide and the like, and as the non-solvent, polyhydric alcohol such as ethylene glycol, triethylene glycol, polyethylene glycol, glycerin, polypropylene glycol and methano-. Alcohols such as alcohol and ethanol can be used. The hollow fiber membrane is hydrophilized in a hydrophilization bath after passing through a coagulation bath and a washing bath. As the hydrophilizing agent, polyhydric alcohols such as glycerin and polyethylene glycol as well as alcohols such as methanol and ethanol can be used. Further, the hollow fiber membrane is wound up through a drying process.

The hollow fiber membrane used in the present invention is characterized by being made of a material in which cellulose triacetate and cellulose diacetate are uniformly mixed and dispersed. When heat treatment is applied to the cellulose triacetate hollow fiber membrane, crystallization progresses, shrinks in the yarn length direction and the radial direction, and the performance remarkably decreases. In the hollow fiber membrane, cellulose diacetate is stretched in the yarn length direction due to orientation. Therefore, by mixing cellulose triacetate with cellulose diacetate, it is possible to suppress the crystals of cellulose triacetate and further suppress the shrinkage, and it is possible to maintain the initial performance after high-pressure steam sterilization.

The weight percentage of cellulose diacetate at the time of mixing is 1 to 50%, preferably 5 to 45%. This is because when the cellulose diacetate is less than 1%, the sieving coefficient of albumin after autoclaving becomes too large, and conversely, when the cellulose diacetate is 50% or more, the sieving coefficient of myoglobin after autoclaving is 0.
It is difficult to exceed 5.

Next, the hollow fiber membrane used in the present invention is 121
The sieving coefficient of albumin after high-pressure steam treatment at 20 ° C. for 20 minutes is 0.1 or less, and the sieving coefficient of myoglobin is 0.1.
There must be more. The sieving coefficient of albumin is 0.1
The sieving coefficient of the above hollow fiber membrane or myoglobin is 0.
Hollow fiber membranes of 5 or more can be produced depending on the spinning dope composition, coagulation conditions and the like. However, when the sieving coefficient of albumin is 0.1 or more, the sieving coefficient becomes too large due to high-pressure steam sterilization, which leads to a large leak of useful albumin. When the sieving coefficient of myoglobin is 0.1 or less, the sieving coefficient after high-pressure steam sterilization does not exceed 0.5, which makes it difficult to remove a medium molecular weight substance such as β2 microglobulin which is a causative substance of dialysis amyloidosis. The sieving coefficient SC of albumin and myoglobin is defined by the following equation. SC = 2 Cfil / (Cin + Cout) where Cfil: filtrate concentration Cin: inlet liquid concentration Cout: outlet liquid concentration.

The hollow fiber membrane according to the present invention is housed in a container having an inlet and an outlet and assembled in a blood purification dialyzer to perform known high-pressure steam sterilization at a temperature of 80 to 140.
C is preferred. Sterilization is not perfect below 80 ° C,
Further, at 140 ° C. or higher, not only the performance of the hollow fiber membrane is significantly deteriorated, but also the members used in the dialyzer are severely deteriorated, and it is practically difficult to manufacture a practical product. From the above, the blood purification dialyzer according to the present invention needs to be sterilized in the range of 80 ° C to 140 ° C. Particularly desirable is 11
Steam sterilization at 5 ° C. for 30 minutes, 121 ° C. for 20 minutes, or 126 ° C. for 15 minutes is preferable.

The container for accommodating the hollow fiber membrane used in the present invention is made of styrene-acrylonitrile copolymer resin for heating at around 80 ° C., and at higher temperatures, polycarbonate, poly-4-methylpentene-1 resin. Manufacturing etc. can be used. The sterilized blood purification dialyzer manufactured by the present invention has the advantages that it is in a sterile state, there is no risk of residual toxicity, and the dialysis performance is sufficiently high, and its effect is greatly exerted in the treatment such as artificial dialysis. What can be done can be provided.

The blood purification dialyzer of the present invention is not limited to artificial kidneys, but can be applied to artificial lungs, artificial livers, artificial pancreas and the like. Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples.

Example 1 Cellulose triacetate / cellulose diacetate =
A spinning dope containing 20% by weight of the mixture of 90/10, 64% by weight of N-methylpyrrolidone and 16% by weight of triethylene glycol was prepared. This was discharged from a double tube nozzle and led to a coagulation bath. Discharge temperature is 130 ° C, coagulation bath temperature is 5
It was 0 ° C. The coagulation bath is N-methylpyrrolidone 24
An aqueous solution containing 6% by weight of triethylene glycol was used. After that, the hollow fiber membrane was washed with a washing bath at about 50 ° C for about 5 minutes.
It is wound up through a drying process at 0 ° C. and about 50% glycerin hydrophilization bath at about 100 ° C. The hollow fiber membrane thus obtained had an inner diameter of about 200 μm and a membrane thickness of about 15 μm. 800 pieces of this hollow fiber membrane were cut into a length of about 25 cm, stored in a container made of polycarbonate resin, and the initial permeation performance was 2 at 121 ° C.
The permeation performance and performance retention after high-pressure steam sterilization for 0 minutes were measured. The results are shown in Table 1.

According to Table 1, in the examples of the present invention, the retention rate of the permeability coefficient after high-pressure steam sterilization is high, and a product that can be sufficiently put into practical use can be obtained. In addition, variations in performance among products were small, and it was not possible to detect bacteria in the products by a sterilization test after sterilization.

Example 2 Cellulose triacetate / cellulose diacetate =
A hollow fiber membrane made of an 80/20 mixture was manufactured under the same conditions as in Example 1. Table 1 shows the performance results of the obtained hollow fiber membranes. As in Example 1, a product that could be put to practical use could be obtained, and no fungus could be detected in the product.

Example 3 Cellulose triacetate / cellulose diacetate =
A hollow fiber membrane made of a 70/30 mixture was manufactured under the same conditions as in Example 1. Table 1 shows the performance results of the obtained hollow fiber membranes. As in Examples 1 and 2, it was possible to obtain a product that could be sufficiently put to practical use, and it was not possible to detect bacteria in the product.

Comparative Example 1 A hollow fiber membrane was produced in the same manner as in Example 1, except that cellulose triacetate was used alone. Table 1 shows the initial permeation performance, the permeation performance after high-pressure steam sterilization at 121 ° C. for 20 minutes, and the performance retention rate of the obtained hollow membrane. Cellulose triacetate alone has an initial permeability coefficient of 80 × 10 −5 cm / sec or more, but it is not practical because the retention rate after high-pressure steam sterilization is low and the dispersion is large.

Comparative Example 2 Cellulose triacetate / cellulose diacetate =
A 40/60 mixture was used to manufacture a hollow fiber membrane in the same manner as in the example. Initial permeability of the obtained hollow membrane, 12
Table 1 shows the permeation performance and performance retention after high-pressure steam sterilization at 1 ° C. for 20 minutes. The mixture of cellulose triacetate / cellulose diacetate = 40/60 had a low sieving coefficient of myoglobin after high-pressure steam sterilization, which was also not practical.

[0021]

[Table 1]

[0022]

EFFECTS OF THE INVENTION The blood purification dialyzer obtained by the method according to the present invention has little deterioration in performance due to high-pressure steam sterilization and its variation, and it is possible to provide a sufficiently sterilized product.

Claims (1)

[Claims] 1. Cellulose triacetate and cellulose diacetate are uniformly mixed and dispersed, and the weight percentage of cellulose diacetate is 1 to 50.
A container having a hollow fiber membrane having an inlet and an outlet having a sieving coefficient of 0.1 or less for albumin after high-pressure steam treatment at 121 ° C. for 20 minutes and a sieving coefficient of myoglobin of 0.1 or more in the range of wt%. A hemodialyzer stored in the.