JPH1043292A - Method for producing semi-wet and dry hemodialyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a semi-wet or dry hemodialyzer and a method for producing the same in which the dialysis performance, residual blood properties, mutagenicity and cytotoxicity of the hemodialyzer are sufficiently ensured. provide. SOLUTION: After thoroughly cleaning the inner wall of the case, the hollow fiber, and the hollow fiber tube plate, and physically removing the filled water from the hemodialyzer filled with water under the condition that the hollow fiber is not dried. , Passing the humectant aqueous solution through the hollow fiber core and outside,
And at this time, the aqueous humectant solution is impregnated inside and outside the hollow fiber such that the aqueous humectant solution seeps out of the outer wall of the hollow fiber, and then the remaining aqueous humectant solution is physically removed under conditions where the hollow fiber is not dried. And sterilized to produce.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a semi-wet or dry hemodialyzer.

More specifically, the inner wall of the module, the hollow fiber, and the hollow fiber tube plate of the hemodialyzer are sufficiently washed,
The present invention relates to a method for producing a semi-wet or dry state containing a humectant inside and outside of a hollow fiber and substantially not containing the aqueous solution in other portions.

[0003]

2. Description of the Related Art Hemodialysis membranes have been used to remove renal functions such as urea and creatinine in the early days as substitutes for renal function of patients with renal function deterioration. A so-called high-performance dialysis membrane has been developed that can efficiently remove medium molecular weight proteins,
It is becoming increasingly important.

[0004] High-performance dialysis membranes are classified into wet, semi-dry, semi-wet (dry-wet) and melt-spinning according to their production methods, and the dry-wet method is particularly used because of its high performance. .

In the production of hollow fibers by such a dry-wet method, a non-water-soluble liquid such as liquid paraffin or isopropyl myristate has been widely used as a core liquid to form hollow portions of fibers. Most of these water-insoluble core liquids can be removed from the inside of the hollow fiber after spinning of the hollow fiber by physical means such as centrifugation or pressure air extrusion, but some core liquid remains on the hollow fiber. Therefore, cleaning has been performed by passing a cleaning solvent such as Freon. However, CFCs have a problem that they are difficult to recover due to destruction of the ozone layer and low boiling point.

Further, urethane resin is used as an adhesive for bonding the hollow fiber to the inner wall of the module. Most of these urethane resins are used by mixing two liquids. However, since the liquid contains an isocyanate group, there is a possibility of adversely affecting safety such as mutagenicity and cytotoxicity. In other words, during dialysis, oligomers of urethane resin or a reaction product of urethane and a humectant due to insufficient curing of the resin, if eluted, may adversely affect the safety of the dialyzer user. .

As a means for solving these problems,
(1) A method of washing and removing the water-insoluble core liquid such as liquid paraffin and isopropyl myristate in the core liquid with isopropanol, and at the same time thoroughly washing the hollow fiber bonding portion, and then rinsing the isopropanol with water (Japanese Patent Application Flat 5
No. 149249), (2) The above water-insoluble core liquid is washed with an aqueous solution of a surfactant, and at the same time, the hollow fiber bonding portion is sufficiently washed, followed by rinsing with water to remove the surfactant and prevent foaming. Method (Japanese Unexamined Patent Publication No. 7-124250)
No.), (3) a method of physically removing the water-insoluble core liquid with water or hot water and at the same time sufficiently washing the hollow fiber bonding portion, and (4) a method of physically removing the water-insoluble core liquid with compressed air containing water droplets. (Japanese Patent Application No. Hei 6-307605) and the like.

[0008] In any of these methods, since a hollow fiber humectant such as glycerin elutes during washing, a water or aqueous solution is filled in the dialyzer, and further sterilized. Provided to users such as hospitals.

[0009] Such a hemodialyzer in a wet state is convenient when used in a hospital or the like, since the operation of wetting the dialysis membrane and removing air bubbles is unnecessary, but is transported / stored in a cold region due to freezing of the filling water. Not only is it difficult to carry out, but also the weight of the hemodialyzer is large and inconvenient to transport / handle. A dialyzer that needs to be in a wet state for some reason other than the core liquid washing also has the same problem.

[0010] The inventors of the present application filed a prior application (Japanese Unexamined Patent Application Publication No.
No. 68524) to produce a semi-wet and dry dialyzer in which a humectant is impregnated inside the hollow fiber after removing the filling water from the dialyzer filled with water and then the humectant is physically removed. Found a way.

However, even in such a dialyzer, there is a problem that the hollow fiber has a portion not impregnated with the humectant aqueous solution, and the quality such as residual blood is somewhat poor.

[0012]

SUMMARY OF THE INVENTION The main object of the present invention is to:
A semi-wet or dry hemodialyzer that solves the problem of residual blood of such a hemodialyzer, has excellent stability against storage and sterilization, and has sufficiently ensured safety such as mutagenicity and cytotoxicity. And a method for manufacturing the same.

[0013]

As a result of intensive studies on such problems, the present inventor has found that a hollow fiber for hemodialysis is built in, and the inner wall of the case, the hollow fiber, and the hollow fiber tube plate are sufficiently washed. , From a hemodialyzer filled with water,
(A) After the filling water in the dialyzer is physically removed under the condition that the hollow fiber is not dried, (b) a humectant aqueous solution is passed through the hollow fiber core and the outside, and The aqueous solution of the humectant is impregnated inside and outside the hollow fiber so that the aqueous solution of the humectant seeps out of the outer wall of the hollow fiber, and then (c)
The aqueous solution of the humectant remaining in the hollow fiber core and the outside is physically removed under conditions where the hollow fiber is not dried. (D) If necessary, the semi-moist hemodialyzer is dried,
The present inventors have found that a hemodialyzer manufactured by removing at least part or most of the water contained in the hollow fiber to obtain a hemodialyzer in a dry state and performing (e) sterilization is effective.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention relates to a hemodialyzer having a built-in hollow fiber for hemodialysis using a water-insoluble liquid.
After washing the core liquid, the inner wall of the module, the hollow fiber, and the hollow fiber tube plate portion remaining on the hollow fiber with a water-soluble organic solvent such as isopropanol, and then with water or with a surfactant aqueous solution, From a hemodialyzer which is once filled with water (or aqueous solution) for some reason, such as washing with water, washing with water or hot water, or washing with a water / pressurized air mixed fluid, a) a step of physically removing the filling water in the hemodialyzer under the condition that the hollow fiber is not dried; (b) passing a humectant aqueous solution through the hollow fiber core and the outside; A step of impregnating the inside and outside of the hollow fiber with the aqueous humectant so that the aqueous solution of the humectant seeps out of the outer wall of the hollow fiber; and (c) removing the aqueous solution of the humectant remaining in the core of the hollow fiber and outside. Physical removal under conditions where the yarn does not dry And (d) further drying the semi-wet state hemodialyzer, if necessary, to obtain at least one of the water contained in the hollow fibers. A semi-wet or dry hemodialyzer and a method for producing the same, characterized in that the hemodialyzer is in a dry state except for a part, preferably most of the hemodialyzer, and (e) sterilization is performed.

Here, the "hemidialyzer in a semi-wet state"
A hemodialyzer containing a humectant aqueous solution in a hollow fiber (peripheral wall portion including a core of the hollow fiber) and not being dried is named,
Preferably, water or the like is present in portions other than the inside of the hollow fiber, for example, the core and outer periphery of each hollow fiber, the gap between the core and the yarn in the hollow fiber bundle or between the outer periphery of the hollow fiber bundle and the inner periphery of the dialysis container. It refers to a hemodialyzer in which an aqueous solution does not substantially remain, and has a moisture content in the range of 10 to 600% by weight, preferably 100 to 350% by weight, based on the weight of the hollow fiber material (dry). . The term "dry hemodialyzer" refers to the above-mentioned semi-moist hemodialyzer which is dried and the moisture content of the hollow fiber is adjusted to the normal temperature (0 to 40 ° C) normal humidity (20
〜80% RH). Although the maximum moisture content varies depending on the type of the humectant and the membrane material, it is preferably dried to 90% by weight or less based on the total weight of the hollow fiber material and the humectant aqueous solution.

In the present invention, the material of the hollow fiber membrane used in the hemodialyzer is not particularly limited as long as it can be formed into the hollow fiber for dialysis. Preferred examples thereof include cellulose esters, Regenerated cellulose, polysulfone, polyacrylonitrile, polycarbonate, polyamide, and the like.Of these, cellulose diacetate, cellulose which is particularly preferable when a non-aqueous core liquid is used in the spinning step is obtained. Cellulose esters such as triacetate are preferred.

The above polymer is uniformly dissolved together with a solvent and a pore-forming agent to prepare a spinning dope (spinning dope), and then a double-tube nozzle is used. On the outside, the spinning solution is supplied, discharged, introduced into a coagulation bath, and solidified by a method of coagulation, for example, a semi-dry semi-wet spinning method, to form a hollow fiber having a dialysis function.

In this case, the water-insoluble liquid used as the core agent includes an aliphatic paraffin having 10 to 30 carbon atoms, a higher fatty acid ester and an aromatic hydrocarbon having 7 to 10 carbon atoms. These may be used alone or in a mixture. Among them, aliphatic paraffins having 16 or more carbon atoms and higher fatty acid esters having 20 or more carbon atoms are often solid at room temperature, and thus need to be heated and melted during spinning.

The water-insoluble liquid particularly preferably used as the core liquid in the present invention is a liquid having a carbon number of 10 to 15 at room temperature.
Liquid paraffin, isopropyl myristate, toluene, xylene and the like. Among these core liquids, they are insoluble in aqueous solution of coagulation bath and completely immiscible with the spinning solution in view of maintaining the shape of the hollow fiber during spinning, smoothness of the inner surface of the hollow fiber, and strength of the hollow fiber. Is most preferably used.

In the present invention, a hemodialyzer is manufactured using the hollow fiber spun in this manner. However, since the water-insoluble core liquid used at the time of spinning is contained in the core of the hollow fiber,
First you need to remove it. Therefore, as much core liquid as possible is removed by physical means such as free fall, compressed air extrusion, and centrifugation. In this case, it is also possible to combine two or more types of means. For example, centrifugal separation can be performed after natural fall and / or extrusion with compressed air, which is effective.

Thereafter, the hollow fiber bundle is stored in the module.
Before or after the adhesive fixation, the core liquid remaining on the hollow fiber is washed and removed. The specific method is as follows. (1) Isopropanol is used to remove the water-insoluble core liquid such as liquid paraffin or isopropyl myristate. A method in which the hollow fiber bonding portion is sufficiently washed at the same time as the washing and removal, and then the isopropanol is rinsed with water. (2) The above-mentioned water-insoluble core liquid is washed with a surfactant aqueous solution and the hollow fiber bonding portion is also cleaned. Washing thoroughly, followed by water rinsing to remove the surfactant and prevent foaming; (3) physically removing the water-insoluble core liquid with water or hot water, and at the same time sufficiently bonding the hollow fiber bonding portion (4) After assembling the module, water is passed through the hollow fiber of the dialyzer to wet the fiber, and then the water-insoluble core liquid is physically removed with compressed air containing water droplets, and simultaneously the medium is removed. And a method in which yarn bonding portion is also sufficiently washed is preferably employed.

Preferably, the core liquid contained in the core part (hollow part) of the spun hollow fiber is first subjected to 80% by weight of the core liquid by physical means such as natural fall, compressed air extrusion and centrifugation.
As described above, preferably after removing 90% by weight or more, the hollow fiber bundle is housed in a dialyzer (case), fixed by adhesion, and a dialyzer (module) is assembled. After this so-called molding step, the core liquid adhering to the hollow fibers in the dialyzer and the hollow fiber bonded portion are washed by the above-described methods (1), (2), (3), and (4). The dialyzer is filled with water (or an aqueous solution to which an additive is added as required) to obtain a wet dialyzer.

According to the present invention, the wet dialyzer manufactured in this manner is used, and at least the following (b)
(C) A semi-wet dialyzer is manufactured by performing each step of (e), and if necessary, the following (a)
By adding the step (d), a dialyzer in a dry state is manufactured.

(A) a step of removing filling water (which may contain an additive if necessary) in the hemodialyzer under the condition that the hollow fiber does not dry; (b) a hollow fiber core portion And passing a humectant aqueous solution to the outside and impregnating the inside of the hollow fiber membrane with the humectant aqueous solution, (c) a core portion (hollow portion) of the hollow fiber
And a step of physically removing the aqueous humectant solution remaining outside under conditions where the hollow fiber does not dry, and (d) drying and removing at least a part, preferably most of the moisture of the aqueous humectant solution of the hollow fiber. Process. (E) a step of sterilizing the dialyzer.

In the above step (a), first, the filling water in the hemodialyzer in a wet state is removed by a physical means such as natural fall, pressurized air extrusion, and centrifugal separation. At this time, it is necessary to carry out under conditions where the hollow fiber does not dry. Here, the “non-dry condition” refers to a state containing 10 to 500% by weight, preferably 100 to 400% by weight of water based on the weight of the hollow fiber material (dry). Here, the means for discharging the filling liquid from the dialyzer includes a natural fall,
Extrusion by compressed air, physical means such as centrifugation are adopted, but these may be employed in combination of two or more types. For example, after natural fall or compressed air extrusion, centrifugation may be further performed. . This step (a) is suitably performed at 0 ° C. to 70 ° C., preferably at room temperature to 50 ° C.

Next, in the above step (b), an aqueous humectant solution is passed through the hollow fiber core and the outside to impregnate the inside of the hollow fiber membrane with the aqueous humectant solution.

As the humectant, a non-toxic, water-soluble, high-boiling, and easily impregnated hollow fiber is used. Suitable specific examples include glycerin, (poly) ethylene glycol, (poly) propylene glycol, and mixtures thereof. These are usually 30
It is used as an aqueous solution of up to 90% by weight, preferably 50 to 80% by weight. The aqueous humectant solution is used at room temperature or after being heated to a low viscosity.

At the time of gamma ray sterilization, it is possible to prevent deterioration of the hollow fiber membrane, the bonded portion of the hollow fiber and the dialysis performance by adding a stabilizer against gamma ray to the aqueous humectant solution of step (b) in advance. . A specific example of such a film stabilizer is phosphoric acid 2
Examples thereof include sodium hydrogen, disodium hydrogen phosphate or a mixture thereof, and a pH adjuster. These are usually 0.02 to 5% by weight, preferably 0.1 to 5% by weight, in the aqueous humectant solution.
It is used by adding 1 to 2% by weight.

Here, in order to impregnate the inside of the hollow fiber with the aqueous humectant solution, the aqueous humectant solution is applied to the blood side at a flow rate of 10 to 2,000.
mL / min, particularly preferably 100 to 1000 mL / min.
And impregnate. Also, in order to impregnate the outside of the hollow fiber, extrude through the membrane from the hollow fiber core,
Or flow the humectant aqueous solution on the dialysate side at 10-2000m
The solution is passed at about L / min, particularly preferably 100 to 1000 mL / min, and impregnated. The temperature of the impregnation treatment in this step is usually from 0 to 70 ° C, preferably from room temperature to 50 ° C. The processing time is 30 seconds to 30 minutes, especially 1 to 30 minutes.
10 minutes is preferred.

As described above, by sufficiently impregnating the hollow fiber membrane with the aqueous solution of the preservative, the problem of poor blood flow (residual blood) due to the breaking of the non-humectant-impregnated yarn has been solved.

After impregnating the inside of the hollow fiber membrane (in the peripheral wall portion of the hollow fiber) with the aqueous humectant solution as described above, the step (c) is performed.
In the above, the humectant aqueous solution remaining in the hollow fiber core and the outside is physically removed under the condition that the hollow fiber is not dried. The physical means employed in this step include the above step (a)
The same means as described above can be adopted.

The above-mentioned step (d) is further applied to the semi-wet dialyzer produced as described above to produce a dialyzer in a dry state. The drying method includes ventilation, heating (hot air heating,
Heating by heating, high-frequency heating, etc.) and steam drying (by solvent vapor etc.) are possible, but a method of ventilating to the dialysate side and / or blood side is preferably adopted from the viewpoint of drying efficiency.

In the present invention, after the semi-wet hemodialyzer or the dry hemodialyzer is manufactured as described above, (e) sterilization can be performed by ethylene oxide, heating, γ-ray irradiation or the like. , Especially dose 10-60KG
It is preferable to sterilize by γ-irradiation.

As a method for evaluating the safety of the hemodialyzer manufactured as described above, the elution test of the adhesive portion of the hollow fiber is performed according to the dialysis type artificial kidney apparatus approval standard (Yakuhin No. 494, June 20, 1983). And the absorbance is defined as a hollow fiber adhesion part UV.

The semi-wet and dry hemodialyzer manufactured according to the present invention has a hollow fiber adhesive portion UV of 0.02 or less.

Thus, according to the present invention, a semi-wet and dry hemodialyzer with very little eluted material from the tube plate is efficiently produced.

[0037]

The present invention will be described more specifically with reference to the following examples and comparative examples. However, these Examples and Comparative Examples are for helping the understanding of the present invention,
These descriptions do not limit the scope of the present invention.

The dialysis performance in the examples was measured as follows.

<Method of Measuring Dialysis Performance of Hollow Fiber> The dialysis performance of the hollow fiber includes water permeability (UFR) and phosphorus dialysis (DA).
Phosphorus), dextran 10,000 dialysis (DA 10,000), and dextran 70,000 screen factor (SC 70,000) were evaluated. For the evaluation, a dialyzer having an effective membrane area of 1.5 m ² was used. Specific measurement conditions are shown below. UFR (ml / m ² / h / mmHg): 35 ° C at a differential pressure of 300 mmH ₂ O
Was determined by measuring the time required for 20 ml of pure water to be filtered under pressure. DA phosphorus (ml / min): 11.52 g of disodium hydrogen phosphate and sodium dihydrogen phosphate in 20 L of RO water
g and NaCl of 180 g were calculated from the difference in the concentration of the aqueous phosphorus solution between the inlet and the outlet when the solution was passed from one end face of the hollow fiber bundle in the dialyzer to the other end face at a flow rate of 200 ml / min.

<Measurement Method of Hollow Fiber Adhered Part UV> As a method for evaluating the safety of the hemodialyzer manufactured as described above, a dialysis type artificial kidney apparatus approval standard (June 20, 1983)
A dissolution test of the hollow fiber bonding portion was performed according to Nippon Kayaku No. 494), and the value was taken as the hollow fiber bonding portion UV.

<Evaluation method of residual blood> The residual blood of the dialyzer was evaluated as follows.

1 L on the blood side of the dialyzer and 1.5 L on the dialysis side
Simulated blood (3 liters of red liquid (RYUDYE-W RED FF3B Dainippon Ink) plus 4 liters of glycerin and 2 liters of water) was passed from one side of the blood side at 200 ml / min for 3 minutes. Water at a rate of 100 ml / min from the other side of the blood.
The solution was passed for minutes. Then, the number of hollow fibers in which the simulated blood remained on the outer periphery of the dialyzer was counted. The smaller the number of hollow fibers with the simulated blood remaining, the better the blood retention during actual dialysis.

Parts and percentages shown in the examples are based on weight unless otherwise specified.

Example 1 A cellulose triacetate hollow fiber bundle spun using liquid paraffin as a core liquid
The suspension was allowed to stand in a drier at 0 ° C., and the liquid paraffin was allowed to fall naturally from one end face of the hollow fiber. After that, the liquid was further centrifuged at 3000 rpm to remove about 95% of the liquid paraffin inside the hollow fiber. Removed. Thereafter, the hollow fiber bundle was housed in a dialysis container (case), the end of the fiber bundle was sealed with urethane, and a urethane curing reaction was performed at 50 ° C. for 20 hours.

After the hollow fiber was wetted by passing 1 L of water through the inner surface of the thus obtained hollow fiber dialyzer, a pressurized air-water mixture (pressurized air containing water droplets) was introduced into the hollow fiber. The air 2
The liquid was passed through at a flow rate of 50 L / min + water at a flow rate of 400 mL / min for 45 minutes to physically remove the liquid paraffin and at the same time sufficiently wash the hollow fiber bonding portion, and then filled with water to form a wet hemodialyzer. Manufactured.

A pressure of 550 mmHg was applied to the dialysate side / blood side of the dialyzer (module) to drain the filling water. Thereafter, a 70% aqueous glycerin solution at a temperature of 37 ° C. is passed from the blood side to the blood side and the dialysate side for 5 minutes at a flow rate of 600 mL / min.
A pressure of 200 mmHg was simultaneously applied to the dialysate side / blood side to remove a 70% aqueous glycerin solution. By further centrifuging at 1000 rpm, glycerin 7 inside the dialyzer is removed.
About 80% of the 0% aqueous solution was removed.

Thereafter, by blowing pressurized air at 37 ° C. from the blood side at a flow rate of 100 L / min for 5 minutes,
15% of the water content of the aqueous glycerin solution adhered to the hollow fiber was removed to obtain a semi-wet state. After that, γ-ray (dose 25K
G) was irradiated and sterilized to obtain a semi-wet hemodialyzer.

Example 2 A cellulose triacetate hollow fiber bundle spun using liquid paraffin as a core liquid
The suspension was allowed to stand in a drier at 0 ° C., and the liquid paraffin was allowed to fall naturally from one end face of the hollow fiber. After that, the liquid was further centrifuged at 3000 rpm to remove about 95% of the liquid paraffin inside the hollow fiber. Removed. Thereafter, the hollow fiber bundle was housed in a dialysis container (case), the end of the fiber bundle was sealed with urethane, and a urethane curing reaction was performed at 50 ° C. for 20 hours.

After 1 L of water is passed through the inner surface of the dialyzer containing hollow fibers thus obtained to wet the hollow fibers, a pressurized air-water mixture (pressurized air containing water droplets) is introduced into the hollow fibers. The air 2
The liquid was passed through at a flow rate of 50 L / min + water at a flow rate of 400 mL / min for 45 minutes to physically remove the liquid paraffin and at the same time sufficiently wash the hollow fiber bonding portion, and then filled with water to form a wet hemodialyzer. Manufactured.

A pressure of 550 mmHg was applied to each of the dialysate side and the blood side of the dialyzer (module) to drain the filling water. Thereafter, a 70% aqueous glycerin solution at a temperature of 37 ° C. is passed from the blood side to the blood side and the dialysate side for 5 minutes at a flow rate of 600 mL / min.
A pressure of 200 mmHg was simultaneously applied to the dialysate side / blood side to remove a 70% aqueous glycerin solution. By further centrifuging at 1000 rpm, glycerin 7 inside the dialyzer is removed.
About 80% of the 0% aqueous solution was removed.

Thereafter, by blowing pressurized air at 37 ° C. from the blood side at a flow rate of 100 L / min for 20 minutes, 90% of the water content of the aqueous glycerin solution adhered to the hollow fibers was removed.
Was removed and dried. After that, gamma rays (dose 25
KG) and sterilized to obtain a hemodialyzer in a dry state.

Comparative Example 1 A cellulose triacetate hollow fiber bundle spun using liquid paraffin as the core liquid
The suspension was allowed to stand in a drier at 0 ° C., and the liquid paraffin was allowed to fall naturally from one end face of the hollow fiber. After that, the liquid was further centrifuged at 3000 rpm to remove about 95% of the liquid paraffin inside the hollow fiber. Removed. Thereafter, the hollow fiber bundle was housed in a dialysis container (case), the end of the fiber bundle was sealed with urethane, and a urethane curing reaction was performed at 50 ° C. for 20 hours.

1 L of 1,1,2-trichloro-1,2,2-trifluoroethane was passed through the inner surface of the thus obtained hollow fiber dialyzer at a flow rate of 400 mL / min for 45 minutes to remove liquid paraffin. did. After that, gamma rays (dose 25
KG) and sterilized to obtain a hemodialyzer in a dry state.

[Comparative Example 2] A hollow fiber bundle of cellulose triacetate spun using gaseous nitrogen as a core was suspended in a dryer at 50 ° C. Thereafter, the hollow fiber bundle was housed in a dialysis container (case), the end of the fiber bundle was sealed with urethane, and a urethane curing reaction was performed at 50 ° C. for 20 hours. After that, it is irradiated with γ-ray (dose of 25KG), sterilized,
The hemodialyzer was in a dry state.

Comparative Example 3 A cellulose triacetate hollow fiber bundle spun using liquid paraffin as a core liquid
The suspension was allowed to stand in a drier at 0 ° C., and the liquid paraffin was allowed to fall naturally from one end face of the hollow fiber. After that, the liquid was further centrifuged at 3000 rpm to remove about 95% of the liquid paraffin inside the hollow fiber. Removed. Thereafter, the hollow fiber bundle was housed in a dialysis container (case), the end of the fiber bundle was sealed with urethane, and a urethane curing reaction was performed at 50 ° C. for 20 hours.

After the hollow fiber was wetted by passing 1 L of water through the inner surface of the hollow fiber storage dialyzer thus obtained, a pressurized air-water mixture (pressurized air containing water droplets) was introduced into the hollow fiber. The air 2
The liquid was passed through at a flow rate of 50 L / min + water at a flow rate of 400 mL / min for 45 minutes to physically remove the liquid paraffin and at the same time sufficiently wash the hollow fiber bonding portion, and then filled with water to form a wet hemodialyzer. Manufactured.

A pressure of 550 mmHg was applied to the dialysate side / blood side of the dialyzer (module) to drain the filling water. Thereafter, a 70% aqueous glycerin solution at a temperature of 20 ° C. was passed from the blood side at a flow rate of 150 mL / min for 10 minutes while the dialysate side was set to a positive pressure so as not to seep into the dialysate side. . Then, by blowing 25 ° C. pressurized air from the blood side at a flow rate of 100 L / min for 1 minute,
About 75% of the 70% aqueous glycerin solution inside the dialyzer was removed to make it semi-wet.

Thereafter, the sample was irradiated with γ-rays (dose of 25 KG) and sterilized to obtain a semi-wet hemodialyzer.

[0059]

[Table 1]

The performances of the thus obtained modules in a semi-wet state (Example 1) and a dry state (Example 2) were all shown in Table 1 in terms of dialysis performance, safety and blood retention. It showed high performance values. Further, as is clear from Table 1, liquid paraffin was used as the hollow part forming agent of Comparative Example 1, and a dialyzer washed and dried using Freon, and gaseous nitrogen was used as the hollow part forming agent of Comparative Example 2. It was found that the value of the hollow fiber adhesion portion UV was lower and the safety was higher than that of the dialyzer that was used.

[0061]

As described above, according to the method of the present invention, the water-insoluble liquid and the hollow fiber tube plate used as the core liquid of the hollow fiber can be formed without using an environmentally destructive solvent such as freon. By washing with a water-soluble detergent such as isopropanol or a surfactant aqueous solution and then washing with water, washing with water or hot water, or washing with pressurized air & water,
It is possible to efficiently manufacture a dialyzer in which the humectant is again applied to the dialyzer in a wet state to make it semi-wet, and a dialyzer in a dry state in which the dialyzer is dried. Such semi-wet and dry hemodialyzers do not have the problem of freezing at low temperatures and have the advantage of being lighter and easier to transport. It has the advantage of excellent stability and the extremely low amount of eluted material from the tube plate. It is possible to provide a hemodialyzer having all the advantages of a very small ratio.

Claims (5)

[Claims] 1. A hemodialyzer having a built-in hollow fiber for hemodialysis, and thoroughly washing the inner wall of the case, the hollow fiber, and the bonded portion of the hollow fiber, and filling the inside with water. After the filling water in the hollow fiber is physically removed under the condition that the hollow fiber is not dried, (b) the aqueous solution of the humectant is passed through the hollow fiber core and the outside, and the aqueous solution of the humectant is then removed from the outer wall of the hollow fiber. And impregnating the inside and outside of the hollow fiber with an aqueous humectant solution, and then (c) removing the aqueous humectant solution remaining in the hollow fiber core and outside under conditions where the hollow fiber is not dried. A method for producing a semi-wet hemodialyzer, comprising physically removing and sterilizing (e). 2. A hemodialyzer which has a built-in hollow fiber for hemodialysis, and which is sufficiently washed with the inner wall of the case, the hollow fiber, and the bonded portion of the hollow fiber and filled with water. After the filling water in the hollow fiber is physically removed under the condition that the hollow fiber is not dried, (b) the aqueous solution of the humectant is passed through the hollow fiber core and the outside, and the aqueous solution of the humectant is then removed from the outer wall of the hollow fiber. And impregnating the inside and outside of the hollow fiber with an aqueous humectant solution, and then (c) removing the aqueous humectant solution remaining in the hollow fiber core and outside under conditions where the hollow fiber is not dried. (D) further drying the semi-moist hemodialyzer to remove at least a part or most of the water contained in the hollow fiber to obtain a dry hemodialyzer;
(E) A method for producing a hemodialyzer in a dry state, wherein sterilization is performed. 3. The extract of the hollow fiber adhesive portion having a UV absorption value of 0.
The method for producing a hemodialyzer according to claim 1 or 2, wherein the value is 02 or less. 4. The method for producing a hemodialyzer according to claim 1, wherein the hollow fiber for hemodialysis is a hollow fiber made of cellulose ester. 5. The method according to claim 1, wherein the aqueous humectant solution is an aqueous solution of any substance selected from glycerin, polyethylene glycol and propylene glycol, or an aqueous solution of a mixture of the above substances. Manufacturing method of hemodialyzer.