JPH0722683B2 - Blood processing device manufacturing method - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for manufacturing a blood treatment device using a selectively permeable hollow fiber. More specifically, the present invention relates to an improved production method by which an excellent blood treatment device with reduced eluents can be stably obtained with high productivity by adopting an efficient washing process.

[Prior Art] A fluid separator using a selectively permeable hollow fiber is used for hemodialysis and
It has been conventionally used practically in reverse osmosis, such as obtaining drinking water from seawater.

In particular, hollow fiber hemodialyzers are currently often used to purify blood of patients with renal failure. This is a dialysis membrane, for example, a large number of hollow fiber membranes are housed in a housing, the patient's blood is flown inside the hollow, and the dialysate is flowed to the outside, that is, the hollow fiber gap, to form a hollow fiber. By dialysis through the wall membrane, waste products in blood are removed to correct the electrolyte concentration, and a pressure difference is applied between the inside and outside of the hollow fiber to remove excess water in the blood. Further, a hollow fiber separator is used to separate plasma from blood alone or to remove a specific component from the plasma to treat autoimmune diseases and the like. Further, there is a hollow fiber type artificial lung for increasing the oxygen concentration in blood by selectively permeating oxygen by flowing blood on one side and oxygen-containing gas such as air on the other side through the hollow fiber. .

Such a hollow fiber type fluid separator should not be one in which harmful substances are eluted during use, for example, in a portion that comes into contact with blood. Since it is likely to occur, a washing process is performed to remove substances that are easily eluted.

However, it takes a relatively long time to reduce the residual amount of the substance that can be eluted in this washing step to a predetermined value. In addition, it is necessary to regulate the flow rate of the cleaning liquid used at that time to a constant value in order to improve the stability of operation, and to increase the production efficiency. Occasionally, a stable washing operation becomes difficult because of clogging.

[Object of the Invention] The present invention is intended to solve the above-mentioned problems, and to provide a method for efficiently producing a blood treatment device of stable quality in a short time. It is what

[Structure of the Invention] As a result of earnest studies for achieving the above object, the present inventor has found that it is very effective to carry out preliminary cleaning in advance under specific conditions and then to carry out full-scale cleaning. They have found the present invention and reached the present invention.

That is, according to the present invention, a container is filled with a bundle of permselective hollow fiber membranes, both ends of the bundle are solidified and sealed with a resin to form a partition wall portion, and the end faces are cut so that both ends of the hollow fiber are cut. In the method of manufacturing a blood processor by assembling by opening the portion and then washing, in the washing step, first, a fluid is supplied to the hollow portion of the hollow fiber at an average flow rate of 1 to 5 cm / sec or more. By doing so, mainly, the inner surface of the hollow fiber membrane is preliminarily washed, and then full-scale washing is performed.

The present invention will be described in more detail below. That is, the hollow fiber membrane used in the present invention has selective permeability, and its materials include celluloses, cellulose esters, polyamides, polyolefins, polysulfones, polyether sulfones, polycarbonates, Examples include polymethylmethacrylate, polyacrylonitrile, polyvinyl alcohol and their copolymers, and mixtures with other substances. A specific example of the copolymer is an ethylene / vinyl alcohol copolymer. Also, although these materials are mainly used in only one type,
Depending on the case, two or more kinds may be used in combination.

Among them, celluloses, polyesters, polysulfones, polyether sulfones, polyacrylonitrile, polymethylmethacrylate, ethylene / vinyl alcohol copolymers and the like are preferable for blood treatment devices. Examples of the cellulose esters include cellulose acetate such as cellulose monoacetate, cellulose diacetate, and cellulose triacetate, cellulose propionate, cellulose butyrate, cellulose acetate butyrate, and cellulose nitrate. Among them, cellulose acetate and cellulose such as cellulose diacetate and cellulose triacetate are particularly preferable.

Among these materials, the effect of the present invention is remarkably obtained particularly in the case of a fluid separator subjected to high-pressure steam sterilization, particularly celluloses, polysulfones, polyethersulfones, etc. used in the production of a blood treatment device. Easy to get caught.

Further, the shape of the hollow fiber of the present invention is not particularly limited, for example, the cross-sectional shape is substantially circular,
One having a fin-shaped protrusion extending in the longitudinal direction on the outer periphery is given. The size is not particularly limited, but in the case of a blood processing device, for example, the outer diameter is 100 to 400.
It is practically preferable that the thickness is about μ and the film thickness is about 5 to 50 μ.

The hollow fiber according to the present invention may be produced by any method such as melt spinning, wet spinning, semi-dry semi-wet spinning and the like.
For example, a stock solution for spinning a hollow fiber membrane (melt or solution) is extruded through a double annular slit of a spinneret into a gas or a spinning bath according to a conventional method, and the hollow portion does not substantially react with the membrane material,
In addition, spinning is performed while keeping a hollow by filling a liquid or gas that does not dissolve it. More specifically, for example, a plasticizer such as polyethylene glycol is added to cellulose diacetate, and the mixture is plasticized and melted by heating and extruded into the air through the double annular slit of the spinneret, and nitrogen gas is injected into the center. From which it is spun into a hollow fiber. Remove plasticizer etc. from this hollow fiber and saponify with alkali if necessary,
A hollow fiber membrane for blood treatment is manufactured.

The resin used as the partition wall material for fixing the ends of the hollow fiber bundle may be any of those normally used for the partition wall of such a fluid separator. For example, in the case of a blood processor, polyurethane is used. Resin and silicone resin are practical, and polyurethane resin is particularly advantageous in terms of safety and price.

The shape of the container in the fluid separator of the present invention is not particularly limited, but a cylindrical shape is preferable,
In particular, a circular cross section is practically advantageous.
The container may be molded by any method, and examples thereof include an injection molding method and a blow molding method. Examples of the material of the container include polycarbonate and polypropylene.

The manufacturing method of the present invention is such that the hollow fiber bundle is loaded into a container, and both ends of the bundle are solidified and sealed with resin at the container end to form a partition wall, and the end face is cut to form the hollow portion. After assembling the fluid separator by opening both ends of the yarn, the washing step is characterized by first performing preliminary washing at a high flow rate.

That is, the pre-washing is to wash the inner surface of the hollow fiber mainly by supplying the liquid to the hollow portion of the hollow fiber at a large average flow rate of 1 to 5 cm / sec to allow the liquid to pass inside the hollow fiber. . The average flow rate of the liquid in this preliminary cleaning is
If it is less than 1 cm / sec, the effect is difficult to obtain, which is not preferable. Further, when the average flow velocity exceeds 5 cm / sec, it is difficult to obtain the cleaning effect only by the increase in the flow velocity, and the pressure in the hollow portion near the inlet becomes too large and the hollow fiber membrane often breaks. Not preferable. A more preferable range of the average flow velocity is the upper limit of 4 cm / sec. The average flow velocity is a value obtained by dividing the flow rate of the liquid supplied to the inlet of the hollow fiber by the cross-sectional area of the hollow portion of the hollow fiber.

The type of liquid used for such preliminary cleaning may be any liquid as long as it does not dissolve the members constituting the fluid separator, and examples thereof include water, lower alcohols, and mixtures thereof. . In the case of a blood treatment device, either water, ethanol or a mixture thereof is preferable from the viewpoint of safety, and water is particularly preferable.

Further, the temperature of the pre-washing is room temperature or higher, and a range not higher than the boiling point of the liquid is practically preferable. This is not preferable in practice because it causes the problem.

Further, the amount of liquid used for the preliminary washing is preferably about 0.1 ml or more per hollow fiber in order to stably obtain the effect of the preliminary washing. The upper limit of the amount of the liquid is about 0.5 ml per hollow fiber, and even if a liquid of more than that is flowed, the cleaning effect corresponding to that is not increased, and the loss of liquid and time is preferable. Often not.
That is, in this pre-cleaning performed at a high flow rate, it is sufficient to carry out the liquid so as to exhibit a predetermined pre-cleaning effect, for example, the effect of removing foreign matter adhering to the film surface, etc. Compared with the cleaning effect obtained, the loss of liquid and time is large, which is not practical. It should be noted that these liquids may be circulated and reused in a part or the whole amount through a filter,
In some cases, ultrasonic cleaning may be used together.

The method for manufacturing a fluid separator according to the present invention is characterized by performing a further full-scale cleaning step after performing such preliminary cleaning. For this full-scale cleaning, use an aqueous solution such as water or physiological saline in the temperature range of 40 to 130 ° C,
It is preferable to use washing of the hollow fiber side of the hollow fiber.

As a specific washing method, for example, a washing method in which water is allowed to flow through the hollow portion of the hollow fiber after preliminary washing, and then water is also passed through the void portion of the hollow fiber and then discharged is given. The amount of water supplied to the hollow portion at that time is practically in the range of about 0.5 cm / sec or more and about 2.5 cm / sec or less, which is represented by the average flow velocity in the hollow portion, but in some cases, It may be out of range.

In addition, as another specific method of full-scale cleaning, for example, the liquid in the fluid treatment device after the preliminary cleaning is discharged as it is,
There may be mentioned a method in which water or an aqueous solution is charged, heat-treated in a temperature range of 40 to 130 ° C., and then replaced with fresh water or an aqueous solution at least once. When the heat treatment operation is performed at a temperature of 110 to 130 ° C., the heat sterilization operation can also be performed.

Incidentally, in these full-scale cleaning, other cleaning methods such as ultrasonic waves may be used together.

The present invention relates to the manufacture of a blood treatment device, which is one type of fluid separator, but for reference, specific applications of other fluid separators include dialysis, ultrafiltration, microfiltration, reverse osmosis, and pervaporation. Examples include liquid separation, oxygen enrichment, gas separation such as artificial lung. Specific examples of the blood treatment device of the present invention include an artificial kidney, an artificial liver, and a plasma separation treatment device, and as a reference example, a body fluid treatment device such as an ascites treatment device and an artificial lung. For fluid separators that require sterilization as in the case of blood processing equipment, heat sterilization operation is required when sterilizing by high pressure steam sterilization, which is superior in safety and does not leave a sterilant like ethylene oxide gas sterilization. At this time, there is little elution from constituent members such as hollow fibers and partition members, and a separator with excellent safety can be easily obtained.

Examples will be given to describe the method of the present invention more specifically, but the present invention is not limited to these examples.

Examples 1 to 3, Comparative Examples 1 and 2 Cellulose hollow fiber membranes obtained by saponifying cellulose diacetate (thickness 25μ, hollow portion diameter 200μ) 9000 pieces were placed in a polycarbonate case and both ends were bonded with polyurethane, Excess polyurethane is cut off and the open end of the hollow fiber is exposed on the urethane adhesive surface, then the header is welded to make a hemodialyzer, and distilled water 1 is passed through the hollow portion at various flow rates, and then collected. Then, it was filtered with a 0.22μ Millipore membrane filter and the amount of the filter residue was measured. In addition, the presence or absence of a leak in the hollow fiber or the like was also examined. The results obtained are shown in Table 1.

[Effects of the Invention] According to the production method of the present invention, it is easy to stably obtain an excellent blood treatment device in which the content of the substance that can be eluted in the constituent members is reduced with good productivity. In particular, it is possible to improve the cleaning process, and it is remarkable to shorten the time or stabilize the regulation of the flow rate of the cleaning liquid.

Claims (3)

[Claims] 1. A container is filled with a converging body of a selectively permeable hollow fiber membrane, both ends of the converging body are solidified and sealed with a resin to form partition walls, and the end faces are cut to both ends of the hollow fiber. In the method for producing a blood processor by assembling by opening the part and then washing, in the washing step, first, liquid is supplied to the hollow portion of the hollow fiber at an average flow rate of 1 to 5 cm / sec. Thus, the method for producing a blood treating device is characterized in that the inner surface of the hollow fiber membrane is mainly preliminarily washed, and then full-scale washing is performed. 2. The pre-cleaning is 0.1 to 0.5 ml per hollow fiber
The manufacturing method according to claim 1, which comprises supplying the liquid at a ratio of. 3. The full-scale washing is characterized by washing at least the hollow portion side of the hollow fiber with water or an aqueous solution in the range of 40 to 130 ° C. The manufacturing method according to the item.