JPH10165773A - Hollow yarn type blood treatment apparatus and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To reduce the residual amt. of air bubbles and impurities in a hollow yarn type blood treatment apparatus to improve work efficiency by respectively setting the concn. of a good solvent of a hollow yarn material remaining in a packing soln. and the voids present in the hollow yarn type blood treatment apparatus to specific values or less. SOLUTION: When a hollow yarn separation membrane is formed, a hollow yarn material is generally dissolved in a good solvent to be spun. As the good solvent, many kinds of solventrs such as dimentylacetamide, dimethylsulfoxide or dimethylformamide can be used. In a process for producing a hollow yarn type blood treatment apparatus, it is necessary to remove the good solvent of the hollow yarn material as impurities by washing. As one index of washing effect, the concn. of the residual solvent in the hollow yarn type blood treatment apparatus can be measured and this concn. is set to 2ppm or less, pref., about 0.5ppm or less. Voids being the index showing the residual amt. of air bubbles of the hollow yarn type blood treatment apparatus are pref. suppressed to 3% or less, more pref., about 1% or less.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hollow fiber type blood processing apparatus and a method for producing the same, and more particularly, to a filling water and a cleaning method for the blood processing apparatus.
More specifically, the present invention provides a hollow fiber type blood processing apparatus in which the amount of air bubbles and impurities remaining in the blood processing apparatus are reduced by efficiently cleaning the blood processing apparatus.

[0002]

2. Description of the Related Art A hollow fiber type blood processing apparatus accommodates a hollow fiber bundle in which a large number of hollow fiber separation membranes are assembled in a cylindrical case, adheres and fixes the hollow fiber bundle to the cylindrical case, and forms a tube. It has caps for blood introduction and exit at both ends of the case, and is widely used for dialysis, filtration, filtration dialysis, plasma separation and the like.

[0003] The hollow fiber type blood processing apparatus is roughly classified,
According to the production process or the post-treatment process, there are two types: one that is kept wet with water or a biologically harmless aqueous solution (hereinafter, wet type) and one that is substantially dry (hereinafter, dry type). In recent years, the first is to perform water washing for the purpose of reducing / removing the residue of the blood processing apparatus, and the second is the wet type for the purpose of preventing deterioration of members from sterilization such as steam sterilization or gamma ray sterilization. Hollow fiber blood treatment device (Japanese Patent Publication No. 55-2)
No. 3620), and studies on a filling solution for a wet type hollow fiber type blood processing apparatus have been disclosed (JP-A-4-338223, JP-A-6-2).
96838, JP-A-7-328112).

A method of cleaning a hollow fiber type blood processing apparatus has been described so far in order to remove residual substances.
As disclosed in Japanese Patent Application No. 0-68862, JP-A-56-15756, JP-A-7-22683, and JP-B-7-29030, the flow rate and temperature conditions of washing water have been studied.

When using a hollow fiber type blood processing apparatus,
Dry blood processing equipment is mainly used for removing residual substances and air bubbles in the equipment and filling with physiological saline, and wet blood processing equipment is mainly used for removing air bubbles and replacing the filling liquid with physiological saline. Priming with physiological saline solution.

[0006] When eluting substances or impurities remain in the blood processing apparatus, it is needless to say that the priming process is troublesome. However, the dry type blood processing apparatus is also priming in order to remove the residue. There is a problem in the work efficiency on the user side by spending more time and saline volume,
Even in a wet blood treatment apparatus, if the degree of filling of water is low, there is room for improving the working efficiency by consuming labor for removing bubbles.

[0007]

SUMMARY OF THE INVENTION In view of the above problems, the present invention is directed to a blood processing apparatus in which the amount of air bubbles and impurities remaining in a hollow fiber type blood processing apparatus are reduced and a residual amount in a hollow fiber type blood processing apparatus is reduced. Another object of the present invention is to provide a manufacturing method for efficiently cleaning an object.

[0008]

SUMMARY OF THE INVENTION A hollow fiber type fluid treatment apparatus according to the present invention is a hollow fiber type fluid treatment apparatus which is filled with water or a biologically harmless aqueous solution and is sealed. The concentration of the good solvent is 2 ppm or less,
Further, the porosity present in the hollow fiber type fluid treatment device is 3% or less.

[0009] The production method of the present invention is characterized in that the hollow fiber type fluid treatment apparatus is washed with water or a biologically harmless aqueous solution degassed to a concentration lower than the saturated dissolved concentration at the washing temperature and filled and sealed. Further, it is preferable to perform the cleaning after aeration of the inside of the blood processing apparatus with carbon dioxide, and it is also preferable to perform cleaning by using water passing through the hollow interior and filtration water passing from the hollow interior to the hollow exterior.

[0010] Further, as cleaning water, the conductivity is 20 μS / c.
m or a high-temperature water of 40 ° C. to 95 ° C. or a biologically harmless aqueous solution can further exert the effect.

It is preferable to sterilize the bacteria remaining in the hollow fiber type fluid treatment apparatus by filling and sealing with an aqueous solution containing hydrogen peroxide and performing radiation sterilization.

[0012]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The hollow fiber type blood fluid treatment apparatus of the present invention and a method for manufacturing the same will be described in detail with reference to the drawings.

FIG. 1 is a sectional view showing an example of a hollow fiber type blood processing apparatus according to the present invention. The hollow fiber type blood processing apparatus is a blood processing apparatus using a large number of selectively permeable fibrous separation membranes 2. The separation membrane is not particularly limited in hollow fiber shape and material, but may be any material. For example, cellulose, polymethyl methacrylate, polyacrylonitrile, polyacetate, polysulfone,
An ethylene vinyl alcohol-based film is preferably used.

In forming such a hollow fiber separation membrane, the hollow fiber material is generally dissolved in a good solvent and spun. Various solvents such as dimethylacetamide, dimethylsulfoxide, dimethylformamide and N-methylpyrrolidone can be used as good solvents.

In the manufacturing process of the hollow fiber type blood processing apparatus, it is necessary to remove the good solvent of these hollow fiber materials as impurities by washing or the like. As an index of the cleaning effect, the residual solvent concentration in the hollow fiber type blood processing apparatus can be measured, and the residual solvent concentration is 2 ppm or less, preferably 0.5 ppm or less.
ppm or less.

In FIG. 1, a fibrous separation membrane 2 is housed in a cylindrical case 1 and fixedly adhered by a potting material 3.
A hollow opening surface is obtained by the blood contact surfaces 5a and 5b. At both ends of the cylindrical case 1 are caps 4a and 4b for blood introduction and introduction.
The processing liquid also has outlets 6a and 6b.

The hollow fiber type blood processing apparatus is a state in which the inside of the blood processing apparatus is hermetically filled with water or a biologically harmless aqueous solution, and is sealed at the blood outlet and the processing liquid outlet by plugs (not shown). Held in state.

When using this hollow fiber type fluid treatment apparatus, first, as a pre-treatment (priming treatment), a physiological saline solution is introduced from a fluid inlet and distributed to a large number of hollow fiber membranes at the opening surface of the hollow fiber. After passing through the inside, it is discharged from the blood outlet to the outside. At this time, voids, air bubbles or the already-filled liquid in the hollow interior are washed away and replaced with a physiological saline solution, and blood as a liquid to be treated is introduced. At the end of the blood processing, the blood in the blood processing apparatus is returned to the body with physiological saline by the same operation as priming.

If impurities or bubbles remain in the blood processing apparatus, there arises a problem that washing and replacement of physiological saline for priming cannot be sufficiently performed. If impurities remain, they may be mixed into the blood.If air bubbles remain, air locks occur in the hollow, and the hollow fiber membrane cannot be used effectively, causing performance degradation,
During prolonged blood treatment, blood clots occur, causing a problem that whole blood cannot be returned to the body (hereinafter referred to as residual blood).

The hollow fiber blood treatment apparatus of the present invention degass the washing water to a concentration lower than the saturated dissolved concentration at the washing temperature to reduce impurities and the amount of remaining bubbles, and furthermore, reduces the conductivity in the washing water to 20 μS. / Cm or less, and more preferably high-temperature water at 40 ° C to 95 ° C is used.

Here, the porosity is an index indicating the amount of residual air bubbles in a wet-type hollow fiber type blood processing apparatus, and is expressed by {(weight filled with water)-(weight after washing and filling)} / (weight filled with water). Where (full water weight) is the inner and outer membrane of the hollow fiber,
It is the weight (including the plug-like member) of the hollow fiber type blood processing apparatus when all the voids of the hollow fiber type blood processing apparatus leading to the holes in the hollow fiber membrane are filled in a liquid-tight manner. The full-water weight is, for example, 3 with a hollow fiber type blood processing apparatus at a flow rate of 500 ml / min.
It can be easily obtained by measuring the weight after passing water through room-temperature water for a day to make the gap liquid-tight. The porosity is preferably 3% or less, more preferably 1% or less.

The dissolved oxygen concentration refers to the concentration of oxygen dissolved in the liquid, and the saturated dissolved oxygen concentration at 25 ° C. and 1 atm is about 8.1 ppm. The dissolved oxygen in the water can be removed by the general means shown. A method of heating to the boiling point and cooling in a sealed state. A method of reducing the pressure to the vapor pressure. A method of bubbling displacement with an inert gas. A method utilizing a contact reaction with a catalyst. A membrane separation method using gas permeation through a membrane.

The method for obtaining the filling water according to the present invention is not limited to the above method. The above method can be applied to obtain quantitatively and continuously. Further, among the techniques mentioned here, in, it is possible to remove (degas) not only dissolved oxygen but also dissolved gas such as dissolved nitrogen, and the object of the present invention can be realized more effectively. Overall, the above method is preferably used, and a combination of the above methods is also possible.

By washing and filling with water in which the dissolved gas is kept low, bubbles in the blood processing apparatus can be completely removed, and the amount of remaining bubbles can be reduced. Further, since air bubbles in the micropores in the hollow fiber film thickness are removed and a liquid-tight state is obtained, mass transfer is facilitated, and cleaning efficiency is improved.

Although the blood processing apparatus is usually sterilized, gamma ray sterilization is widely used because there is a problem in heat resistance of the housing member and there is an advantage in safety because there is no residue at the time of sterilization. In the case of filling with deoxidized water as described above, there is a possibility that the amount of oxygen radicals at the time of gamma ray irradiation is small and the sterilization effect is reduced. That is, there is a possibility that the required irradiation dose to kill the bacteria increases (the D value increases). In this case, as described in the present application, an increase in the D value can be suppressed by adding a hydrogen peroxide solution and irradiating with gamma rays. The aqueous hydrogen peroxide also has a bacteriostatic effect during storage from washing of the blood processing apparatus to gamma sterilization.

In washing with high-temperature water at 40 ° C. to 95 ° C., which is another requirement of the present invention, air bubbles become apparent in the washing water. Therefore, it is necessary to take into account the solubility of gas in water. In the case of dissolved oxygen concentration,
ppm or less, at 50 ° C 5.5 ppm or less, 60 ° C
Is preferably 4.5 ppm or less at 80 ° C.

The electric conductivity is one index of the degree of purification of the washing water, and the requirements of the present invention can be achieved by using distilled water, ion-exchanged water, or RO water treated with a reverse osmosis membrane.

FIG. 2 shows an example of the washing water producing apparatus.

The biologically harmless aqueous solution is, for example, a physiological saline solution or a glycerin solution containing distilled water, ion-exchanged water or RO water as a main component, but is not particularly limited.

Next, when the blood processing apparatus is passed through the cleaning apparatus with the washing water, the air in the blood processing apparatus is replaced with carbon dioxide having a high solubility in water in advance, so that the remaining air bubbles are reduced. Can be further reduced, and the cleaning efficiency can be further improved.

As for the washing method, known washing methods such as a method of washing by passing washing water through the hollow interior and the outside of the hollow, or a method of filtering and passing water from the inside of the hollow to the outside of the hollow may be used. The cleaning method of (1) requires a large amount of cleaning water, and the latter cleaning method may cause a problem that the short path of the hollow fiber and the cleaning of the potting bonding portion become insufficient. Therefore, it is effective to use a combination of the water washing of the hollow interior shown in FIG. 3 and the filtration water washing shown in FIG. At a certain interval, washing may be performed by alternately switching between the water washing and the filtration water washing of the hollow interior a plurality of times.

Finally, the inside of the blood processing apparatus is kept wet by closing the opening with a plug-like member after being filled with water or an aqueous solution. At this time, it is preferable that the amount of voids in the blood processing apparatus be minimized and sealed,
Further, the sealing member is not limited to a shape material, but a material having high oxygen permeability is desirably avoided because the effect of the present invention cannot be sufficiently obtained.

[0033]

EXAMPLE A polysulfone-based hollow fiber bundle having an inner diameter of 200 μm, an outer diameter of 280 μm, a number of hollow fibers of 13056, and an effective membrane area of 1.6 m ² was housed in a cylindrical case, and then polyurethane resin was injected under centrifugation. Then, both ends of the tubular case and the hollow fiber bundle were bonded and fixed, respectively, and caps for drawing in and out were attached to both ends to obtain an experimental hollow fiber type blood processing apparatus, and then washed. The full water weight was determined by measuring the weight of a hollow fiber blood treatment apparatus at 500 ml / min for 3 days with normal temperature water and plugging. The theoretical full water weight at this time was 579.4 g.

Washing of the hollow fiber type blood treatment apparatus was performed with water treated by the washing water producing apparatus shown in FIG. At this time, the conductivity was 11 μS / cm. As a deaerator, a commercially available membrane type deaerator (manufactured by Miura Kogyo Co., Ltd., DOR-3)
000C). The dissolved oxygen concentration was measured as an index of the degree of degassing and adjusted to a desired concentration.
The temperature was set to a desired temperature condition by heat exchange. Further, the hydrogen peroxide concentration was added so as to be 30 ppm. Regarding the washing, the washing time was set to 35 minutes in each case, and the washing was started after passing carbon dioxide into the blood processing apparatus before passing the washing water. The conditions were changed and implemented.

A hollow fiber type blood processing apparatus which has been washed and filled,
The following evaluation was performed. Measurement of removal amount of air bubbles: The blood processing apparatus was weighed, and the amount of filled water was measured. The heavier the weight, the more bubbles were determined to be removed. The weight before washing was also measured and handled. Measurement of the amount of impurities removed: After irradiating the blood processing apparatus with gamma rays of 25 kGy, the filling water was extracted, and the good solvent concentration (dimethylacetamide (DMAc)) of the polysulfone-based hollow fiber material remaining in the filling water was measured by GC-MS. did.
It was determined that the lower the DMAc concentration, the less the impurities.

Example 1 Degassing was performed so that the concentration of dissolved oxygen became 0.5 ppm, and the temperature was raised to 90 ° C. to obtain washing water. As a washing method, after washing with water in the hollow for 3 minutes, subsequently, washing with water through filtration is performed for 3 minutes. This was carried out five times, and after washing for a total of 30 minutes, the mixture was cooled with washing water at 30 ° C. for 5 minutes and stoppered.

Example 2 Degassing was performed so that the dissolved oxygen concentration became 2 ppm,
The mixture was heated to 0 ° C. to obtain washing water. As a washing method, after washing with water in the hollow for 3 minutes, subsequently, washing with water through filtration is performed for 3 minutes. This was carried out five times, and after washing for a total of 30 minutes, the mixture was cooled with washing water at 30 ° C. for 5 minutes and stoppered.

Example 3 Degassing was performed so that the dissolved oxygen concentration became 5 ppm, and the temperature was reduced to 5 ppm.
The mixture was heated to 0 ° C. to obtain washing water. As a washing method, after washing with water in the hollow for 3 minutes, subsequently, washing with water through filtration is performed for 3 minutes. This was carried out five times, and after washing for a total of 30 minutes, the mixture was cooled with washing water at 30 ° C. for 5 minutes and stoppered.

COMPARATIVE EXAMPLE 1 The temperature was raised to 40 ° C. without performing deaeration operation, and used as washing water. As a washing method, after washing with water in the hollow for 3 minutes, subsequently, washing with water through filtration is performed for 3 minutes. This is 5
After washing for a total of 30 minutes, the system was cooled with washing water at 30 ° C. for 5 minutes and stoppered.

Comparative Example 2 The temperature was raised to 80 ° C. without deaeration, and used as washing water. As a washing method, after washing with water in the hollow for 3 minutes, subsequently, washing with water through filtration is performed for 3 minutes. This is 5
After washing for a total of 30 minutes, the system was cooled with washing water at 30 ° C. for 5 minutes and stoppered.

The results are summarized in the following table. -------------------------------------------------------Experiment No. Weight of blood processing apparatus A Porosity DMAc concentration [g] [%] [Ppm] −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− Example 1 577.1 0.4 0.08 Example 2 577.8 0.3 0.15 Example 3 578.2 0.2 1.50 Comparative Example 1 573.3 1.1 2.60 Comparative Example 2 561.3 3.1 0.55 ------ −−−−−−−−−−−−−−−−−−−−−−−−−−−− Note: Porosity [%] = (579.4-A) /579.4×100

[0042]

As described above in detail, according to the hollow fiber type blood processing apparatus and the method of manufacturing the same of the present invention, the amount of air bubbles and impurities remaining in the blood processing apparatus can be reduced.

[Brief description of the drawings]

FIG. 1 is a cross-sectional view showing an example of a hollow fiber type fluid treatment device.

FIG. 2 is a schematic flow chart showing an example of a cleaning water production device.

FIG. 3 is an explanatory view showing a flow path of washing water in washing water through the inside of the hollow of the hollow fiber type blood processing apparatus.

FIG. 4 is an explanatory diagram showing a flow path of washing water in filtration water washing of a hollow fiber type blood processing apparatus.

[Description of Signs] 1: Cylindrical case 2: Hollow fiber membrane 3: Potting material 4a: Cap for blood introduction 4b: Cap for blood derivation 5a, b: Opening surface 6a, b: Nozzle for treatment liquid derivation 7: Pre Filter 8: Degassing device 9: RO membrane 10: Heat exchanger 11: Hollow fiber type fluid treatment device

Claims (8)

[Claims] 1. A hollow fiber type fluid treatment apparatus filled and sealed with water or a biologically harmless aqueous solution, wherein the concentration of a good solvent in a hollow fiber material remaining in the filling liquid is 2 ppm or less, and The porosity present in the fluid treatment device is 3
% Or less. 2. The hollow fiber type fluid treatment apparatus according to claim 1, wherein said hollow fiber material is a polysulfone resin. 3. A method for manufacturing a hollow fiber type blood processing apparatus, comprising washing the hollow fiber type fluid processing apparatus with water or a biologically harmless aqueous solution degassed to a concentration lower than the saturated dissolved concentration at the washing temperature, filling the closed state, and sealing. . 4. The method according to claim 1, wherein the water or the aqueous solution has an electric conductivity of 20 μS /
The method for producing a hollow fiber type blood processing apparatus according to claim 3, wherein the diameter is not more than cm. 5. The method for producing a hollow fiber type blood processing apparatus according to claim 3, wherein the apparatus is washed with high-temperature water at 40 ° C. to 95 ° C. or a biologically harmless aqueous solution. 6. The method for producing a hollow fiber type blood processing apparatus according to claim 3, wherein the blood processing apparatus is washed after aeration with carbon dioxide. 7. The method for producing a hollow fiber type blood processing apparatus according to claim 3, wherein the apparatus is filled with an aqueous solution containing hydrogen peroxide, sealed, and sterilized by radiation. 8. A method for manufacturing a hollow fiber type fluid treatment apparatus, wherein washing is carried out by using water passing through the hollow interior and filtration water passing from the hollow interior to the hollow exterior.