JPH0290986A - Removing process for endotoxin in preparation of pure water - Google Patents

Abstract

PURPOSE:To stably prepare pure water without endotoxin or super-pure water by treating deionized water with a mixture of a carbonic adsorbent prepared by carbonizing a porous globular crosslinked polymer and ion exchange resin. CONSTITUTION:A porous globular crosslinked copolymer prepared by copolymerizing styrene, divinylbenzene and the like is carbonized or carbonized and activated to prepare a carbonic adsorbent of superior resistance to wear and physical strength. Said carbonic adsorbent is mixed in a mix bed ion exchange resin column of strong basic cation exchange resin and/or strong acid anion ion exchange resin or combined on the upper section of the mix bed. Removal of endotoxin can be carried out stably and securely for a long period of time by treating deionized water prepared by the ion exchange treatment process by means of said column.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention is directed to a method in which a porous spherical crosslinked synthetic polymer is carbonized or carbonized to activate endotoxin derived from bacteria growing or multiplying within a pure water production system. The present invention relates to a method for removing endotoxin in pure water production using a mixed system of a carbonaceous adsorbent and a strongly basic anion exchange resin and/or a strongly acidic cation exchange resin.

[Conventional technology]

Endotoxin (bacterial endotoxin) is a complex phospholipid polysaccharide (lipopolysaccharide) that exists as a cell membrane component of Durham-negative bacteria, and is a typical pyrogenic substance (pyrogiene).

Each national pharmacopoeia stipulates that water for injection must not contain pyrogenes as well as bacteria.

In addition, with the increasing degree of integration of semiconductor devices, the purity of the pure water used for this has been improved to the maximum, so-called ultrapure water, and the number of viable bacteria, which is the source of pyrogen, is 0.02/
A strict standard of mρ or less is required.

In order to obtain pure water that does not contain pyrogenes, pharmacopoeically purified water is usually purified by distillation, but pure water obtained by one round of distillation is tested using the Limulus test [horseshoe crab hemocyte extract, Limulus amoebosite].・Lysate (Limulus Amerbocyte Lys)
Test 1 by gelation reaction between ate) and endotoxin
The test results are often positive.

Therefore, recently, membrane separation methods have come into use as seen in Japanese Patent Nos. 989058 and 738632. Membrane separation methods are usually incorporated as an element in extremely expensive ultrapure water production systems, rather than being used alone.Specifically, membrane separation methods are used to remove not only pyrogenes but also various ions, organic substances, etc. After passing city water containing a large amount of water through activated carbon and ion exchange resin,
In this method, water is stored and further treated with an ultraviolet sterilizer for sterilization, a regenerating mixed bed type ion exchange resin tower, and then a permeable membrane such as an ultrafiltration membrane or a reverse osmosis membrane.

Bacteria are inherently proliferative, so even if they are sterilized, they will be trapped within the system, especially on the surface of the permeable membrane, and as the number of dead bacteria trapped and killed increases, the endotoxin concentration will decrease. It is presumed that this is a cause of unexpected performance deterioration of the permeable membrane, such as rapid clogging of the permeable membrane.

It is known that when the pyrogen-free water obtained in this way is frequently discharged from the water under aseptic control, it is easily contaminated with bacteria and endotoxins are produced within a short period of time.

Accordingly, there is a strong demand for chemicals, special adsorbents, etc. that can easily and effectively obtain endotoxin-free water.

Various attempts have been made to treat pyrodiene by adsorption methods.

For example, ion exchange resins, synthetic adsorbents, and various activated carbons include porous ion exchange resins such as Amberlite 200 and IRA-938 (Amberlite is a registered trademark of Rohm and Haas). According to the Journal of the Chemical Society of Japan (1973) No. 81547-1553, there are some effects on synthetic adsorbents, such as Amberlite XAD resin, and activated carbon. It has been reported.

[Problems to be Solved by the Invention] An object of the present invention is to provide a method for removing endotoxin to an ultra-trace concentration in pure water production.

Another object of the present invention is to provide an improved method for removing endotoxins that enables the production of ultrapure water or ultra-superpure water for various uses.

[Means for Solving the Problems] The above objects of the present invention are achieved by the following endotoxin removal method.

Deionized water from the ion exchange resin treatment process is combined with a carbonaceous adsorbent obtained by carbonizing or carbonizing a porous spherical crosslinked polymer and an ion exchange resin, particularly a strongly basic anion exchange resin and/or a strongly acidic anion exchange resin. This is a method for removing endotoxins in pure water production, which is characterized by treatment using a mixed system with a cation exchange resin. Here, as the carbonaceous adsorbent obtained by carbonizing the porous spherical crosslinked polymer by thermal decomposition, JP-A-51-126390, JP-A-49-
No. 53594, JP-A-53-50088, JP-A-52
Carbonaceous adsorbents produced by the methods listed in Japanese Patent Application Laid-Open No. 51-63619, etc. are desirable.

As this porous spherical crosslinked polymer, a copolymer consisting of a monovinyl monomer and a polyvinyl monomer is generally most preferable.

The above monomers are copolymerized by a known JV turbidity polymerization method to obtain a spherical copolymer.

Specifically, one made of styrene and divinylbenzene is the most well-known.

Of course, the present invention can also be completed with copolymers consisting of monovinyl monomers other than these and other poly(nyl) monomers.

In order to obtain porosity, it is important to add a sufficient amount of known additives to impart porosity during suspension polymerization.

Typical additives for this purpose are called precipitants,
A solvent that dissolves in the monomer and does not swell the resulting copolymer,
Also, it is called a swelling agent, and it is a solvent that dissolves in the monomer and swells the produced copolymer, or a mixed solvent in which the above-mentioned swelling agent and precipitant coexist, and furthermore, these swelling agents and this swelling agent and a homogeneous liquid phase. an organic liquid consisting of a monovinyl linear polymer capable of forming and soluble in the monomer mixture;
Examples include insoluble polymeric substances such as polyalkylene glycol that are inert to the produced copolymer, but are not limited to these, and it is of course possible to use other known pore-forming agents. It is.

Even if the porous crosslinked copolymer produced by such a method is an ion exchange resin obtained by subjecting it to sulfonation, chloromethylation, etc. by a known method as the case may be, and then amination, the above-mentioned Like porous copolymers, these are preferred.

These porous spherical crosslinked copolymers may be commercially available. For example, commercially available Amberlite ion exchange resin series or synthetic adsorbent series may be used.
Furthermore, many commercially available products such as Diaion (registered trademark of Mitsubishi Chemical Corporation) and DOWEX (registered trademark of Dow Chemical Company) can of course be used.

The desired adsorbent can be produced by carbonizing the porous spherical crosslinked copolymer thus obtained using a known method.

If this porous spherical crosslinked polymer is rendered infusible using sulfuric acid, nitrogen dioxide, chlorine, etc., and then thermally decomposed at 300 to 900°C, the desired carbonaceous adsorbent can be obtained.

The adsorbent thus obtained can be used as it is, but it is also appropriate to use it after further activation with steam, aqueous zinc chloride solution, etc., if desired.

Specific examples of such commercially available adsorbents include Rohm
Ambersorb manufactured by & Haas
The bl series is known.

This adsorbent has a spherical shape, low ash content, and is characterized by high wear resistance and physical strength.

These two-layer characteristics have special significance for the treatment of endotoxins in pure water.

Due to these characteristics, in addition to the effective adsorption of endotoxin by this adsorbent, it is possible to treat endotoxin in pure water without degrading the water quality.

In other words, ordinary activated carbon for water treatment not only becomes a breeding ground for bacterial growth due to its amorphous shape, but also has low physical strength or abrasion resistance, so it can be crushed into fine particles that remain in the treatment system. This causes problems such as deterioration of water quality.

The biggest difference between this adsorbent and commercially available powdered or granular activated carbon is that its physical structure is fundamentally different from activated carbon.The skeletal structure of the porous spherical polymer remains unchanged even after carbonization and activation. It should be noted that it is retained as is.

It is presumed that this difference contributes to the large difference in the adsorption amount of endotoxin.

Regarding the adsorption and removal of endotoxins using ion exchange resins alone, there have been only a few attempts, but according to the above-mentioned Journal of the Chemical Society of Japan, ``Removal of pyrogenic substances by ion exchange, adsorption, and membrane permeation,'' among the tested resins, So, as a cation exchange resin, MR pear type strong acid cation exchange resin is good, and as an anion exchange resin, gel
Strong salt type basic pear type dimethylethanol ammonium type 7 anion exchange resin or ultra MR type strongly basic (type I trimethyl ammonium type) anion exchange resin has good treatment results, i.e., as a bacterial pyrogen. of ribobosaccharite 0.33 ppm (330 ng/m℃) or 3,
It is said that water treated by column treatment using an ion-exchange resin containing 3 ppm (3,300 ng/mff) of raw water passed a pyrogenicity test using rabbits.

However, it is stated that a stable treatment effect could not be expected when cycles were repeated using a mixed bed of these ion exchange resins.

The inventors have conducted extensive studies regarding the removal of pyrodiene in water, and have filed a patent application (Japanese Patent Application No. 76094/1989) regarding a carbonaceous adsorbent itself for removing pyrodiene, and a method for removing endotoxin in pure water production using the same. No.) has already been carried out.

According to the results of the inventors' research, a trace amount (50 ng) of
/ mρ or less) In the batch adsorption removal of dissolved endotoxin using a strongly basic anion exchange resin, the strongly basic anion exchange resin is extremely effective in removing endotoxin in pure water, and is more fine than the gel type. Porous type with abundant pores and large surface area, MR type, etc.
It has been found that Type I resins are more effective than Type I resins.

Currently, membrane treatment plays a major role in the production of pyrogen-free water for medicine and pharmaceutical use.

In addition, regarding the removal of bacteria, which is a major problem in the production of ultrapure water for the semiconductor industry, sterilization using ultraviolet sterilizers and physical removal using membranes are the mainstream methods, but bacteria in the ultrapure water production equipment system Durham-negative bacteria, which are endotoxin-producing bacteria, are the primary bacterial species, and when they die, endotoxin is released, so there is a movement to regulate this.

There is no doubt that the ion exchange resins built into pure water or ultrapure water production equipment have also played a role in removing endotoxins, but as mentioned above, as the cycles are repeated, This had the disadvantage that the treatment effect was unstable.

However, with the removal method of the present invention, endotoxin removal can be carried out extremely stably, reliably, and effectively over a long period of time.

A simple and practical method is to use strongly acidic cation exchange resins and/or strong Either the synthetic spherical carbonaceous adsorbent of the present invention is mixed into a mixed bed of basic anion exchange resin, or a column preliminarily charged with a mixture of these is used in the apparatus.
The desired purpose can be achieved only by integration just before the point of use.

Instead of mixing, a kind of double bed may be used in which a synthetic carbonaceous adsorbent is placed on top of a hot bed of ion exchange resin.

The ion exchange resin used in the present invention is currently a commercially available gel type, MR type, or porous type strongly acidic and/or strong type that can be used for producing pyrogen-free water or ultrapure water. It is a basic ion exchange resin. However, it is inconvenient that the Chatilon value (the crushing strength value measured by a crushing strength tester) is substantially 0 kg/cm''.

Synthetic carbonaceous adsorbents have extremely high physical strength, so when used in combination with ion exchange resins, which have extremely low physical strength, they are crushed during use, resulting in pyrogen-free water and fine particulate matter. This is because it contaminates the ultrapure water production equipment system.

It is also possible to use ordinary activated carbon instead of this spherical synthetic carbonaceous adsorbent, but since its shape is amorphous, it becomes a breeding ground for microorganisms and cannot withstand use. do not have.

[Effects of the Invention] According to the present invention, the carbonaceous adsorbent is simply mixed into the existing mixed bed type ion exchange resin column, and there is no need to separately equip a new column. Furthermore, contrary to the use of an ion exchange resin alone, a synergistic effect occurs, and endotoxin-free pure water or ultrapure water can be stably provided.

Furthermore, when the present invention is incorporated into existing pyrogen-free water or ultrapure water production equipment, it can be expected to reduce the load on the membrane and extend its life.

[Example] EXAMPLES The present invention will be specifically described below with reference to Examples.

Synthesis example 1 of carbonaceous adsorbent 5.0 g of polyvinyl alcohol, 2 g of carboxymethyl cellulose, and 156 g of NaC were dissolved in distilled water at 1.5°C, and 200 g of styrene and divinylbenzene (purity 5
A mixture of 1,132 g of 9%, 240 g of butanol, and 1.5 g of benzoyl peroxide was added, and the mixture was heated at 85°C with stirring for 6 hours.
Allowed time to react. Obtained porous spherical crosslinked polymer 4
0 g in 500 g of 15% oleum at 110°C.
The sulfonation reaction is carried out for a period of time, and then)1. SO4
It was then washed with water and dried.

9 at a rate of 300°C/H in N2.
The temperature was raised to 50° C. for firing.

The apparent specific gravity of the fired product is 0.5 and the pore volume is 0.6 cc.
/g.

The porous spherical carbon of this fired product was heated to 80°C in a steam atmosphere.
After 2 hours of activation treatment at 0°C, the surface area was 110
A carbonaceous adsorbent with 0rrI2/g was obtained.

Synthesis example 2 of carbonaceous adsorbent 5 g of polyvinyl alcohol, 2.5 g of carboxymethyl cellulose, 1.5 g of NaC1S6 and 1.5 g of distilled water
℃, 200 g of styrene, divinylbenzene (
Add a mixture of 132 g of commercially available product (59%), 240 g of toluene, and 1.5 g of benzoyl peroxide, and stir at 85°.
The reaction was carried out at C for 6 hours.

40 g of the obtained porous spherical polymer was subjected to a sulfonation reaction in 500 g of 15% oleum at 110°C for 6 hours, and then washed with sulfuric acid, water, and dried.

Then 950° at a rate of 300°C/Hr in N2
The temperature was raised to C and fired.

The porous spherical carbon of this fired product had an apparent specific gravity of 0.55 and a pore volume of 0.5 cc/g.

This was activated at 800°C in a steam atmosphere for 2 hours,
A carbonaceous adsorbent with a surface area of 1020 rn'/g was obtained.

Example 1 Tap water was used as raw water, and it was constructed with a granular activated carbon column, a gel type cation exchange resin column, a gel type anion exchange resin column, and then a group of ion exchange resin columns made of a mixed bed type porous spherical crosslinked polymer. When a deionized water production device was operated intermittently at a room temperature of about 20°C for about 4 hours each time and a water intake of 100°C, an average of 1.5 ng of endotoxin/endotoxin was found in the deionized water after about 2 weeks. It leaked out at a level of mI2.

The purity of water for about 1 minute at the start of intermittent operation reached 182 MΩcm in-line, below TOCtoo ppb, and there was no problem at all in terms of performance as a deionized water production device. Therefore, the piping of the treated water was branched into six pipings, the first piping system was filled with 60 nl of the carbonaceous adsorbent of Synthesis Example 1 into a glass column with a diameter of 11 cm and a height of 75 cm, and the second piping system was divided into six piping systems. In a glass column with a diameter of 2.0 cm and a height of 75 cm, carbonaceous adsorbent of Synthesis Example 1 (60 mj2) and strong acidic cation exchange resin Amberlite IR-124H type 4 were added.
0 m℃, and the strong basic anion exchange resin Amberlite IRA-402BL leaf type 80 mj2 was filled with a sufficiently mixed mixture, and the diameter of the third piping system was 2.0 cm and the height was 75 mm.
60 nl of the carbonaceous adsorbent of Synthesis Example 2 in a cm glass column.
, Amberlite IR-124) (Type 40n+j2, and Amberlite IRA-402BL O) Type I 80
The fourth piping system, a glass column with a diameter of 2.0 cm and a height of 75 cm, was filled with a mixture of Amberlite IRA-402BL OH type 120 mff and Ambersorb XE-34060 mj2 sufficiently mixed. The diameter of the fifth piping system], the 6 cm height 75 cm glass column was 14 type 40 of Amberlite jR-124.
mj2 and amber light IRA-402BL OH type 8
The sixth piping system, a glass column with a diameter of 1.6 cm and a height of 75 cm, was filled with a sufficiently mixed mixture of 0 mj2 and a weakly acidic cation exchange resin Amberlite IRC-50H type 40 m.
°C and weak basic anion exchange (δ1 fat Amberlite I
RA-93 free base type 80n+J2 was thoroughly mixed and packed so that the packed layers in each column were approximately the same height, and the flow rate was 5V = 8 (8 times the amount of adsorbent per hour). Water flow was started when the treated water passed through the dish.

Detection limit for en[-toxin: 0. Treatment (2) at O1 ng/mff was as shown on the next page.

1st column 2nd column (fl) 3rd column 4th column Example 2 Tap water containing 40 ng/mff of pyrodiene was used as raw water, granular activated carbon column, gel type cation exchange resin column, gel type anion exchange resin Deionized water treated with a mixed-bed porous ion exchange resin tower was placed in a water storage tank at 200°C. The deionized water production device on the raw water supply side automatically operates to maintain this stored water (I) at a constant storage level of 200 ml.

Ultraviolet sterilizer, 2℃ regenerative mixed bed ion exchange resin tower,
In a small ultrapure water production system for laboratory use, which passes through an ultrafiltration membrane, then to a faucet at the point of use, and unused water is returned to a water storage tank, each run is approximately 100°C and has a purity of 18
．． One week after the start of water sampling at 2M Q cm, water was sampled from the sampling point between the regenerated mixed bed ion exchange resin tower and the ultrafiltration membrane and analyzed, and endotoxin was found to be 0.15 ng.
/mj2 existed.

Therefore, this regenerated mixed bed type ion exchange resin tower was removed and a new MR type ion exchange resin Amberlite 200C was installed.
) 1:l mixture of type I and type IRA-9000111.
When a column with a diameter of 8 am and a height of 50 cm filled with a mixture of Ambersorb XE-347500mJ2 and Ambersorb /m
It was less than j2.

the above'? In a comparative example in which the AR type ion exchange resin mixture was used alone at 2°C, the outflow of endotoxin exceeded the detection limit after one month.

The endotoxin concentration was measured using a horseshoe crab blood cell extraction product manufactured by Wako Pure Chemical Industries, Ltd. and a toxinometer manufactured by the same company.

In addition, the method for regenerating the ion exchange resin used was that the cation exchange resin was treated with 4% HCI at a rate of 1OO125 per 1°C of resin.
V=4, regenerated at room temperature, anion exchange resin was 4% Na
Regeneration with OH at 20 equivalents per β resin at 5V = 4.50°C was followed by washing until no traces of 11cI and NaOH were observed, respectively.

When converting the ion-exchange resin into a regenerated type, endotoxin-free pure water was used as water.

Applicant: Tokyo Organic Chemical Industry Co., Ltd. Agent Waka Hayashi Tadashi

Claims (1)

[Claims] Deionized water obtained from the ion exchange resin treatment step is carbonized or carbonized and activated by a porous spherical crosslinked polymer, a carbonaceous adsorbent, a strong basic anion exchange resin, and/or a strong acid. A method for removing endotoxin in pure water production, which is characterized by treatment using a mixed system of cation exchange resins.