JPS6099260A - Autoclave pasturization of cellulose ester hollow fiber typeseparation membrane - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on an autoclave sterilization method for cellulose ester-based porous hollow fiber membranes, which is widely applicable to separation membranes for medical purposes such as artificial kidneys. be.

Traditionally, hollow fiber separation membranes have the characteristic of being compact in volume compared to their membrane area, and are useful not only for industrial applications such as single-lens membranes, but also for direct body fluid collection, such as in artificial kidneys. It is widely used for medical purposes such as: In the latter case, the compact volume has a great deal to do with the advantage of being able to reduce the burden on those in charge.

However, in order to use split membranes for medical purposes,
It is most important to maintain the separation membrane in a rectangular (closed p) shape, and therefore the separation membrane used must be sterilized. When decomposition membranes were first used for medical purposes, separation membranes were sterilized by formalin, but this method had biosafety issues such as formalin properties, and gradually sterilization methods were changed to ethylene oxide adsorption using ethyl material. As clearly shown, there remains a concern that the gas may remain in the separation membrane. Therefore, autoclave sterilization, which eliminates the risk of residual sterilizing agent during sterilization of separation membranes, has begun to attract attention.

However, although sterilization methods that require high-temperature and high-pressure treatment, such as autoclave sterilization, have the advantage of not leaving any sterilizing agent behind, they have serious inherent problems such as changes in the membrane structure of many separation membranes and changes in membrane performance. Ta. Such changes in membrane structure due to autoclave treatment were particularly remarkable in cellulose ester.

The present inventors conducted intensive research to apply autoclave sterilization to cellulose ester separation membranes, which are widely used in medical applications from the viewpoint of biocompatibility. Resulting crystallization - Focusing on the fact that molecular rearrangement changes membrane properties, the water component coexisting in the cellulose ester separation membrane is replaced with a polyhydric alcohol that does not contain substantially water, and the porous part of the membrane is It was found that filling the cellulose ester substantially completely with the polyhydric alcohol combined with plasticization of the membrane material can prevent irreversible structural changes in the cellulose ester. 1. Autoclave sterilization method for cellulose ester-based porous separation membranes was completed.

That is, the present invention is characterized in that a cellulose ester porous hollow fiber type separation membrane is subjected to a treatment in which the porous portion of the membrane is filled with a polyhydric alcohol that does not substantially contain water, and then sterilized in an autoclave. This is an autoclave sterilization method for cellulose ester hollow fiber separation membranes.

The polyhydric alcohols used are those that are harmless to the human body, such as glycerin, 1.4-butanediol, 1,3-butanediol, polypropylene glycol, polyethylene glycol, etc. 1. If water is present, cellulose ester hollow fiber type separation is used. Both dehydration of the membrane and change in membrane properties are undesirable because they reduce autoclave resistance. Further, as the polyhydric alcohol used in the present invention, a pure polyhydric alcohol having a moisture content of 5% by weight or less and 95% by weight or more is preferred, and among these, glycerin gives preferable results.

In addition, the cellulose ester porous hollow fiber type separation membrane used in the present invention is prepared by dissolving a polymer such as cellulose p-diacetate or cellulose triacetate in a solvent or in a solvent and a swelling agent. It is produced by spinning from an orifice, solidifying) and washing with water, and there are no particular limitations. In short, it is sufficient to use cellulose ester as the polymer and make it porous by an appropriate method.

Such a cellulose ester porous hollow fiber type separation membrane needs to be treated so that the porous portion of the membrane is substantially filled with the above-mentioned polyhydric alcohol. Although such a treatment can be carried out even in the form of a filamentous separation membrane, it is advantageous to assemble the filamentous separation membrane into a module and carry out the process as such. As such a treatment method, for example, a multi-stage substitution means of multivalent aba-' as shown below is employed. That is, in the first step, the module containing the film formation is subjected to a cyclic substitution operation with the polyhydric alcohol, and then in the second step, the polyhydric alcohol is added to the module in One-paJ! By performing the contacting operation in step 8, the porous portion of the membrane is substantially filled with the polyhydric alcohol. More specifically, when the hollow internal volume (briming volume) of the hollow fiber separation membrane is V-, the polyhydric alcohol used must be at least 2 V- or more in the first stage circulation operation. 1 more preferably 3v-gov-. In this first step, it is preferable to carry out a cyclic catalytic displacement operation for 5 to 60 minutes using the above-mentioned amount at a flow rate of 7 m/win to 10 m/cm. Furthermore, in the second step, it is necessary to use a polyhydric alcohol of at least 2 V- or more, preferably 5 V- or more,
+y/mn to 3Va (One with a flow rate of /+nin
- It is ideal to perform a replacement operation with p&88. After this multi-stage replacement process for polyhydric alcohol is completed, the polyhydric alcohol remaining inside the hollow interior of the separation membrane of the separation membrane module is removed by centrifugal deliquification, etc., and then washed with a fluorocarbon solvent to remove the polyhydric alcohol. Processed to ensure no alcohol remains. Thereafter, this fluorocarbon solvent is vaporized and the next autoclave sterilization is performed.

Autoclave sterilization follows the method of the Japanese Pharmacopoeia. In other words, 115℃ x 30 minutes, 121" o x 20 minutes, 126℃ x
Select the 15 minute condition.

As described above, by adopting the method of the present invention, it has been possible for the first time to produce a cellulose ester porous hollow fiber partial detachment module with high biocompatibility without causing any change in membrane structure, that is, without causing deterioration of membrane performance. . The Ht membrane module produced in this way can be advantageously used in medical fields such as artificial beasts. Examples of the method of the present invention will be described below, but the present invention is not limited to these examples in any way.

Example 1 A film with an inner diameter of 200 μm and a film thickness of 25 μm manufactured by a conventional method.
A module was manufactured using a morrose ester porous hollow fiber type separation membrane with a porosity of 50%.

In this module, zovi (v indicates the hollow internal volume of the membrane) substantially water-free pharmacopoeia concentrated glyceptin was used.
Circulatory displacement was performed at a flow rate of Vllll/[1IIn for 0 minutes. Subsequently, 10 V- of essentially water-free pharmacopoeically concentrated glycerin was added at a flow rate of V-tt/m.
Replacement operation was performed with ss. After this, the glycerin filled in the hollow interior of the membrane is removed by centrifugation, the remaining glycerin is removed using a fluorocarbon solvent that is incompatible with glycerin, and the remaining glycerin is removed by drying at 50°C to remove the fluorocarbon solvent. It was vaporized. In this way, a cellulose ester hollow fiber type separation membrane module was produced in which the porous portion of the separation membrane was filled with glycerin that did not substantially contain water. This module was sterilized in an autoclave at 121°C for 20 minutes to produce a final product.

About this product TJFR retention rate, inulin (molecular weight 5
200), dextran (molecule j11゜64
000) was measured to evaluate membrane performance. The results are shown in Table 1.

Table 1 Note) The comparative examples in Table 1 are cases in which the concentrated glycerin used in this example was further impregnated with water as shown in Table 1.

In addition, the glycerin water content, VFR retention rate,
Inulin inhibition rate and dextran inhibition rate were measured as follows.

(1) Glycerin moisture content (%) Measured by Karl Fischer method (li) TJ FR retention rate (feed Calculated by.

(110 inulin inhibition rate C%) and dextran inhibition rate (support)) Comparative Example 4 Using a colorimetric method using the anthrone sulfuric acid method, which is an analysis method for polysaccharides.If the module was not autoclaved in Example 1, UFR retention Although the module membrane performance was 100%, inulin rejection 16%, and dextran rejection 90%, this module could not be used in medical applications because it had no sterilization effect.

Example 2 Autoclave sterilization was performed in the same manner as in Example 1, except that an artificial kidney dialysis separation membrane having an inner diameter of 200 μm, a lI'J thickness of 25 μm, and a porosity of 50% was used. The film performance of the Tu-treated product was evaluated as shown in Table 2.

Table 2 In addition, the performance of the separation membrane module before sterilization is UFR retention rate of 100%, inulin rejection rate of 59%,
Although it showed a dextran inhibition rate of 97%, it has no sterilization effect at all, so it cannot be used for artificial kidney applications.

Patent applicant: Toyobo Co., Ltd.

Claims (2)

[Claims] (1) A cellulose ester porous hollow fiber separation membrane is pretreated by filling the porous portion of the membrane with a polyhydric alcohol that does not contain substantially water, and then sterilized by autoclaving. Autoclave sterilization method for cellulose ester hollow fiber separation membrane. (2) The autoclave sterilization method according to claim (1), wherein the polyhydric alcohol has a water content of 5% by weight or less and a purity of 95% by weight or more.