JPS62179540A - Nonadsorptive hydrophilic membrane - Google Patents

Abstract

PURPOSE:To obtain the titled hydrophilic membrane which excels in water permeability and retentivity and stain resistance and can be used continuously and repeatedly and can be easily handled, by graft-polymerizing a monomer having a neutral OH group with a porous membrane obtained from, e.g., a polyolefin. CONSTITUTION:A graft-polymerizable monomer having at least one neutral OH group or a functional group as its precursor (e.g., allyl alcohol or vinyl acetate) is graft-polymerized with a hydrophobic porous membrane obtained from a polyolefin, an olefin/halogenated olefin copolymer, polyvinylidene fluoride or the like to obtain the titled hydrophilic membrane having a three-dimensional network structure and a neutral OH group content of 0.1-5 meq per g of the membrane and being in the form of a flat film, a tube, especially, a hollow yarn of an inside diameter of 0.1-10mm and a thickness of 0.05-5mm.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention provides a hydrophilic solution suitable for sterilization and purification of fungicidal particles of injections, infusions, bulk stock solutions, or water used for various drugs in the pharmaceutical industry, etc. The present invention relates to a porous membrane and a method for manufacturing the same.

[Conventional technology]

Conventionally, in the pharmaceutical industry, many microfilters have been used to remove bacteria or particulates from various drug solutions produced therein.

Hydrophilic membranes consisting of many types of flat membranes (disc-shaped) or pleated cartridges have been used in these microfilters. The reason for this is that most of them are used only once and most are discarded.
It can only be applied to so-called disposable type applications, and cannot be applied to applications that are used repeatedly or continuously or intermittently over a long period of time. For this repeated use or long-term use, hollow fiber microfilters have recently been put into practical use. Due to the advantage of its membrane shape, this hollow fiber microfilter is capable of a parallel flow system called cross flow, which prevents suspended matter (bacteria or particulates) from adhering to the membrane surface, and reverses the flow. The p excess performance can be restored by washing or the like.

The appearance of this hollow fiber microfilter has dramatically expanded the field of membrane purification, including application to so-called bioreactors and sterilization enzymes. However, since most of the hollow fiber membranes mentioned above are made of polyolefin membranes and are inherently hydrophobic, it is necessary to temporarily wet the membrane with ethyl alcohol etc. beforehand when using K in the actual solution. Furthermore, it is necessary to prevent the membrane from drying during the process as much as possible, and there is a possibility that dissolved components may be adsorbed to the membrane during the process, which is not preferable.

In reality, infusions and injections are relatively expensive, so K.

It is necessary that the hold-up amount is as small as possible and that handling is simple, and therefore it is becoming an essential condition that K can be used immediately as it is even in a dry state.

In addition to this polyolefin hollow fiber membrane, a polyvinyl alcohol modified membrane is also coated, but in addition to its inherent mechanical weakness, the mechanical strength becomes even weaker once it dries, making it unstable for repeated use. It is virtually impossible to use it as a liquid, and it is rarely used in final filters of infusion products.

On the other hand, many methods have been proposed for making polyolefin hollow fiber membranes hydrophilic by chemically modifying them. Specific examples include sulfonation with fuming or anhydrous L-chlorosulfonic acid, or grafting of acrylic acid, etc. to polyolefin. This method is a method of introducing a sulfone group or a carboxyl group by using a method of introducing a sulfonic group or a carboxyl group.This method achieves the purpose of making it hydrophilic, and is suitable for producing some pure water and providing additional functions such as ion adsorption. There is.

However, when trying to purify a drug solution containing proteins, amino acids, salts, etc. using these membranes,
The r-liquid often deteriorated in quality due to adsorption to the membrane, reaction, etc. For this reason, 1. Despite its excellent mechanical performance, it has been impossible to use purified KFi in infusions, injections, etc. [Problems to be solved by the invention] The present invention When removing and purifying bacteria or particulates from pharmaceutical solutions such as industrial infusions and injections, it can be used repeatedly for a long time, and can be used immediately with the membrane in a dry state. It is said that it provides an extremely useful microfilter membrane that does not deteriorate in quality.

[Failure to solve the problem]

As a result of intensive research into microfilter membranes that solve the above problems, the inventors of the present invention found that the problems can be achieved by the following means.

That is, side chains containing neutral hydroxyl groups are grafted onto a porous membrane whose base membrane material is polyolefin, a copolymer of olefin and halogenated olefin, or polyvinylidene fluoride, and the neutral hydroxyl group content is It has been found that the problem can be solved very effectively by a non-adsorptive hydrophilic membrane with an average pore size Q of 0, / to j milliequivalents per duram of membrane, 01N5μ, and a porosity of -〇 to ro%. .

The present invention will be explained in more specific detail below.

The membrane to be grafted in the present invention must be a hydrophobic porous membrane such as polyolefin, a copolymer of olefin and halogenated olefin, or polyvinylidene heptadide, which is necessary as a base membrane. Helps maintain mechanical properties.

Here, as specific examples of the above-mentioned polyolefin, a copolymer of an olefin and a halogenated olefin, polyolefin resins such as polyethylene, polypropylene, polybutylene or a mixture of two or more of the above-mentioned resins, or ethylene,
A copolymer made of a mixture of two or more of propylene, butylene, hexene, tetrafluoroethylene, and chlorotrifluoroethylene, or a polyvinyl fluoride IJden resin is used.

Next, the monomers that are crafted into these hydrophobic films have one or more neutral hydroxyl groups (alcoholic hydroxyl groups) or functional groups that can be used as precursors of hydroxyl groups, and
Must be graftable. Specifically, esters of acrylic acid or methacrylic acid and polyhydric alcohols such as 2-hydroxyethyl-acrylate and co-hydroxyethyl-methacrylate, alcohols having unsaturated bonds such as hyalyl alcohol, and vinyl acetate, Examples include enol esters such as vinyl propionate. Particularly preferred are alcohols and enol esters having unsaturated bonds, such as allyl alcohol, by grafting onto the hydrophobic membrane, or by grafting vinyl acetate or the like, followed by hydrolysis. A non-adsorptive hydrophilic membrane having a desired side chain containing a neutral hydroxyl group can be obtained. Moreover, unlike the case of using 2-hydroxyethyl acrylate, the product obtained in this way does not have an ester bond, so the side chain is chemically extremely stable, and it can be used under conditions such as acids and alkalis. Chemical changes do not occur easily even under low temperatures.

The concentration of the hydroxyl groups in the side chains thus obtained can be adjusted as desired, but as an effect of the present invention, the concentration of hydroxyl groups in the side chains obtained in this way is 0.7 to 1 mm, preferably 1 to 3 mm per 7 grams of membrane.
Milliequivalents are required.

Here, film/gram refers to the fairly macroscopic weight f of the film:
cf refers to a value based on a reference, and does not refer to the amount of M extracted from, for example, only a part of the film surface or a part of the inside. In order to make the base film hydrophilic while retaining its excellent mechanical properties, it is easier to achieve the goal by grafting preferentially to the pore surface (as much as possible). Therefore, the meaning of 1 gram of the base film here refers to a value measured evenly over the entire surface of the film, and does not mean the weight from a very microscopic viewpoint.

The porous membrane grafted according to the present invention has an average pore diameter in the range of 0.01μ to Sμ. Here, the average pore size refers to the nine values obtained by the method described in ASTM FJ #-70, which is usually called the air flow method. measure,
It is determined from that ratio.

The range of the average pore diameter in the present invention is determined from the viewpoint of practical performance, and any other range is inappropriate in terms of permeation rate, particle removal effect, etc.

Next, the porosity of the porous membrane obtained by the present invention is 10 f.
It is in the range of Here, the porosity was determined by immersing the membrane in a liquid such as water in advance, then drying it, and measuring the weight change before and after that. Porosity values outside the range of the present invention are unfavorable in terms of permeation rate, mechanical properties, etc.

The pore structure of the base membrane, which is the base of the porous membrane obtained in the present invention, can be obtained by various forming processes. Etching methods, etc., can also be applied; however, the pore structure, for example, that of the Japanese Patent Publication Publication No. 59-3729
No., Special Publication No. 10-937 and Special Publication No. 7-17
Preferably, those having a three-dimensional network structure formed by the microphase separation method or mixed extraction method described in Kou No. 10 are preferred. Especially 1 Tokkai Shoj! The significance of the present invention became clear through the establishment of the manufacturing technology for the structure disclosed in Japanese Patent Publication No. -1310211, and a method for manufacturing a material with excellent performance that could not be obtained with the prior art was achieved.

The shape of the porous base membrane is applicable to any of flat membrane, tube, and hollow fiber membrane shapes, but for the purpose of the present invention, the shape of the porous base membrane is 0. It is preferable to use a hollow fiber type having a shape of / to 10 mm and a thickness of 0 to 5 to j mm.

Methods for grafting the functional groups of the hydrophilic membrane of the present invention onto the base film include methods such as chemical treatment, but the most effective method is to irradiate the base film with ionizing radiation.

This method rarely causes chemical deterioration of the base film, does not easily produce free polymer, and the porous film produced in this way has excellent mechanical and chemical properties.
Good filtration performance too.

Ionizing radiations used include alpha rays, beta rays, gamma rays, accelerated electron beams, and X-rays, but electron beams or gamma rays are practically preferred. There are two methods for graft polymerization: a simultaneous irradiation method in which radiation is irradiated to the porous substrate and the monomer in the coexistence of the monomer, and graft polymerization is performed; There is a pre-irradiation method in which one-contact reaction is carried out to effect graft polymerization, but in the simultaneous irradiation method, as the graft polymerization of the monomer to the porous substrate progresses, only the monomers that do not participate in the graft polymerization are homopolymerized, resulting in the porous The pre-irradiation method is preferred since it poses the problem of blocking the pores in the substrate.

In the pre-irradiation method, the base material is irradiated with radiation before contacting the monomer with the porous base material, and the temperature of the microcuff is kept at 10 °C or less until it comes into contact with the monomer, and the temperature is kept at 50 °C or less.
Graft polymerization is preferably carried out by contacting with monomers at a low temperature of 15°C to 50°C. If the porous base material is not stored at a low temperature after irradiation with radiation, the generated radicals will rapidly decay, and the number of radicals will be reduced to half when exposed to vinegar for 30 minutes at room temperature (°C). Furthermore, at the same time, the generated radicals react with a trace amount of adsorbed oxygen, resulting in a defect that impairs the heat and chemical resistance of the target substance. In addition, when the graft polymerization temperature is 30°C or higher, a homopolymerized monomer that does not participate in the graft polymerization is generated, which may block the pores of the porous substrate, or monomers that are not extracted in the post-treatment process after the reaction. A problem arises in that the heat 11 compound flows out after becoming hydrophilic and causes secondary pollution.

Hereinafter, the structure and effects of the present invention will be specifically described with reference to Examples, but these are not intended to limit the present invention.

〔Example〕

Example 1 and Comparative Example 1. A composition of 23.1 parts by weight of silicic acid powder, 41 parts by weight of dibutyl phthalate (DBP), and parts by weight of polypropylene resin powder [Asahi Kasei Polypropylene-M723/'J Coi, sH] was prepared in advance. After pre-mixing, extrusion into a hollow fiber shape with an inner diameter of Q7m and a thickness of a2swmo using a 30mm mini-screw extruder, /, /, /
, -) +7 After being immersed in chloroethane [70 Rosen vG (trade name)] for 60 minutes to extract DBP, it was further immersed in a caustic soda tio% aqueous solution at a temperature of 60°C for about -0 minutes to extract fine powder silicic acid. Then, I washed and dried it.

One electron accelerator (pressure voltage/,
! ; MeV, electron beam current/mA) under a nitrogen atmosphere at 700 KGY, and then the dissolved oxygen was preliminarily reduced to 0. Grafting was carried out by exposure to vinyl acetate vapor below IP.

This graft membrane was further reacted with a 30% caustic nose aqueous solution at 10°C for 211 hours, and the average pore size was 0. /! μ, porosity 6
2%, hydroxyl group! An example membrane of fk71 grams per millimeter was obtained.

For comparison, an untreated polypropylene hollow fiber membrane extruded and extracted under the same conditions as in Example 1 was prepared from JP-A-Sho! t-571
Sulfonation was carried out in the same manner as in Publication No. 36, Example B), and the sulfone group Q, ! ; Mi II fz /
/gram membrane (average pore diameter θ 16μ, porosity 6j) a membrane of Comparative Example 1 was obtained.

In addition, in the example membrane, an untreated membrane after extracting DBP and silicic anhydride was used as a comparative example λ membrane in the following experiment.

Here, the hydroxyl groups of the Example membrane and the sulfone groups of the Comparative Example membrane were determined below.

[Quantification of hydroxyl groups]

After the alkali-treated membrane was sufficiently washed with water and dried, an appropriate amount of acetic anhydride-viridi/mixture (l:3 volume ratio) was added, and the mixture was heated at 10° C. for 265 hours in a sealed container.

After cooling, water was added to convert excess acetic anhydride to acetic acid, a mixed indicator of cresol red and thymol blue was added, and titration was performed using standard alkali hydroxide.

[Quantification of sulfone group]

The sulfonated porous membrane was immersed in a /N HCI aqueous solution to form H-type, washed with water, then immersed in a K/N CaCl2 aqueous solution, and titrated with phenolphthalein as an indicator using the liberated HCI t Q-NkhOH aqueous solution.

Above 31! Table 1 shows the transient characteristics of the J film.

(Margin below) @ /) 23℃, differential pressure 7tQ■ Coffee measurement.

e) Initial water permeability ratio for a wet membrane after drying for 2j hours in a 100'C constant temperature bath.

3] Dow Uniform Latex 0. / Capture efficiency from light transmittance in Z liquid.

4j) / % L - Transmittance of IJ Gin solution to the p solution of the stock solution.

The data in Table 1 shows part of the excellent chemical purification effect of the Examples of the present invention.

Example 2.3 and Comparative Example 3 Etele/-tetrafluoroethylene copolymer (trade name Akuon COP) 21.2 parts by weight, chlorotrifluoroethylene oligomer (trade name Daifloy # *20)
j7.4'1iiL part, silicone oil (product name K
F-94) After premixing 4.5 parts by weight and 111.9 parts by weight of finely divided silica, extrusion was performed using almost the same extruder as in Example/, and chlorotrifluoroethylene oligomer, silicone oil, and finely divided silica were extracted. Same operation as Example/, average pore diameter αlψμ, porosity 62%.

An example membrane having a hydroxyl base content of da, θ milliequivalents/l gram was obtained.

Separately, allyl alcohol was grafted in place of vinyl acetate in Example 1, and S, S milliequivalent//example membrane of crumb membrane (average pore diameter 0./lμ, porosity (.0chi)
I got it.

The P performance of the two examples membranes was as shown in Table 2. For reference, a comparative ml of the modified polyvinyl alcohol membrane (Kuraray 5F-uO/) applied thereon is shown.

In addition, when the pa rate and retention rate were measured by passing the γ-aminobutyric acid model solution of Example 3 and Example 3 through the membrane,
” After encountering n?/n?P, the retention rate was 7o respectively.
, 63%. After that, it was washed with a caustic soda aqueous solution and steam sterilized, and the filtration rate was measured.
The fact that the VC was recovered by 717,117% and 91%, respectively, indicates that the membrane of the present invention can be used repeatedly in actual drug filtration.

〔Effect of the invention〕

The membrane of the present invention has a high water permeability retention rate after drying and has little contamination from the outside during use, so it can be used repeatedly when used as a final filter for 4 liquids, and can be incorporated into a plant. Since it can be used continuously, the purification equipment is very easy to handle in chemical liquid purification, and it is highly effective in terms of labor savings.

Claims (7)

[Claims] (1) A porous membrane in which the material of the base membrane is polyolefin, a copolymer of an olefin and a halogenated olefin, or polyvinylidene fluoride is grafted with a side chain containing a neutral hydroxyl group, and contains a neutral hydroxyl group. Rate is,
A non-adsorptive hydrophilic membrane with an average pore size of 0.01 to 5 microns and a porosity of 20 to 80%, with an average pore size of 0.1 to 5 milliequivalents per gram of membrane. (2) The non-adsorptive hydrophilic membrane according to claim 1, wherein the side chain is a vinyl alcohol monomer or polymer, or an allyl alcohol monomer or polymer. (3) The pore structure of the membrane has a substantially three-dimensional network structure, and the membrane shape has an inner diameter of 0.1 to 10 mm and a thickness of 0.005 to 5 mm.
The non-adsorptive hydrophilic membrane according to claim 1, which is in the form of hollow fibers. (4) Side chains containing neutral hydroxyl groups are grafted to a porous membrane whose base membrane material is polyolefin, a copolymer of olefin and halogelated olefin, or polyvinylidene fluoride, and neutral hydroxyl group content is 0.1 to 5 milliequivalents per gram of membrane, and the average pore size is 0.0
In a method for producing a non-adsorptive hydrophilic membrane with a porosity of 1 to 5μ and a porosity of 20 to 80%, neutral A method for producing a non-adsorptive hydrophilic membrane, which comprises grafting a grafting monomer having a hydroxyl group. (5) The method for producing a non-adsorptive hydrophilic membrane according to claim 4, wherein the grafting monomer having a neutral hydroxyl group is allyl alcohol. (6) Side chains containing neutral hydroxyl groups are grafted to a porous membrane whose base membrane material is polyolefin, a copolymer of olefin and halogenated olefin, or polyvinylidene fluoride, and neutral hydroxyl group content is 0.1 to 5 milliequivalents per gram of membrane, and the average pore size is 0.0
In a method for producing a non-adsorptive hydrophilic membrane with a porosity of 1 to 5μ and a porosity of 20 to 80%, neutral 1. A method for producing a non-adsorptive hydrophilic membrane, which comprises grafting a grafting monomer having a hydroxyl group precursor, and then deriving the precursor into a neutral hydroxyl group. (7) Non-adsorptive property according to claim 6, wherein the grafting monomer having a neutral hydroxyl group precursor is vinyl acetate, and the induction of the precursor to the neutral hydroxyl group is hydrolysis of an ester bond. A method for producing a hydrophilic membrane.