JPH078355B2 - Endotoxin removal method in ultrapure water - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] The present invention carbonizes or activates a porous spherical crosslinked synthetic polymer of endotoxin derived from a bacterium that grows or proliferates in a pure water production system. The present invention relates to a removal method using a carbonaceous adsorbent.

[Conventional technology]

Endotoxin (bacterial endotoxin) is a complex phospholipid polysaccharide (lipopolysaccharide) that exists as a cell membrane component of Gram-negative bacteria, and is a representative pyrogen (pyrodiene).
Is.

When this is mixed directly into the human body blood via intravenous injection, etc., it causes a strong fever reaction, vasoconstriction, increased sensitivity to adrenaline, accelerated blood coagulation and subsequent decrease, and in some cases leads to death in Schock. . Therefore, the bureaus of each country stipulate that water for injection should not contain pyrogenic substances as well as bacteria.

To obtain water that does not contain a pyrogenic substance, usually, distilled water of the pharmacopoeia is distilled. However, one-time distillation requires the Limulus test [blood cell extract of Limulus amebocyte lysate] and endotoxin. Quantitative method based on the gelation reaction in [1]. In the past, treatment with powdered and / or granular activated carbon and various ion exchange resins was attempted as a technique for removing exothermic substances, but leaks often occur due to load changes of exothermic substances and stable treatment effects cannot be expected. It was Recently, Japanese Patent 989,058 "Method for obtaining a sugar refined liquid that does not contain a pyrogen", Japanese Patent 738,632
Membrane separation methods using permeable membranes have come to be used, as described in "Method of obtaining aqueous solution for injection free of pyrodiene and microorganisms by permeation treatment".

The membrane separation method is incorporated into one element of the ultrapure water production system. Specifically, city water containing a large amount of exothermic substances, various ions, organic substances, etc. is passed through activated carbon and ion exchange resin, and then stored. Further, it is a method of treating with an ultraviolet sterilizer for sterilization, a regenerative mixed bed type ion exchange resin tower, and then a permeable membrane such as an ultrapermeation membrane or a reverse osmosis membrane. However, bacteria are originally proliferative, and there are bacteria that can grow and proliferate even in ultra-pure water-level low nutrient water, and even if they are sterilized, they remain in the system, and endotoxin increases with the number of dead bacteria. It is presumed that it may cause an unexpected deterioration of the performance of the membrane, such as rapid clogging of the permeable membrane at the water intake, by following the rise. Therefore, there is a strong demand for a method of effectively preventing the contamination of water with endotoxin.

[Problems to be solved by the invention]

An object of the present invention is to provide a method for removing endotoxin so as to have an ultratrace concentration in the production of pure water.

Another object of the present invention is to provide an improved method for removing endotoxin which enables the production of ultrapure water or ultrapure water for various purposes.

[Means for solving problems]

The above object of the present invention is achieved by the following endotoxin removal method.

A series of steps of receiving deionized water containing endotoxin from the ion exchange resin treatment process in a water tank, followed by ultraviolet sterilization, treatment with regenerative mixed bed ion exchange resin and membrane treatment with ultrafiltration membrane or reverse osmosis membrane In the method for producing ultrapure water, which is a carbonaceous adsorbent obtained by carbonizing a porous spherical crosslinked polymer or a carbonaceous adsorbent activated by carbonization, and maintaining the skeletal structure of the porous spherical crosslinked polymer as it is. The method for removing endotoxin in ultrapure water, which comprises placing the adsorption step using the carbonaceous adsorbent after the water storage tank but before the membrane treatment step.

The carbonaceous adsorbent obtained by carbonizing the porous spherical crosslinked polymer by thermal decomposition is described in JP-A-51-126390 and JP-A-49-126390.
It is produced by the method described in JP-A-53594, JP-A-53-50088, JP-A-52-30799 and JP-A-51-63619.

Generally, the porous spherical polymer is most preferably a copolymer composed of a monovinyl monomer and a polyvinyl monomer.
This is produced by a known suspension polymerization method of the above-mentioned monomer to obtain a spherical copolymer.

Specifically, those composed of styrene and divinylbenzene are the most well known. The present invention can of course be achieved with other monovinyl monomers and other polyvinyl monomers. In order to obtain porosity, it is important to carry out the polymerization by adding known additives sufficient to obtain porosity during suspension polymerization. As this typical additive, a solvent that is soluble in a monomer called a precipitant and does not swell the produced copolymer, and a solvent that is soluble in a monomer called a swelling agent and swells the produced copolymer. solvent,
Alternatively, a mixed solvent in which the swelling agent and the precipitating agent coexist, further, an organic liquid composed of the swelling agent and a monovinyl linear polymer capable of forming a uniform liquid phase with the swelling agent, and soluble in a monomer mixture, Examples thereof include insoluble polymers that are inert to the copolymer, such as polyalkylene glycol, but are not limited to these, and it is naturally possible to use other known agents capable of forming porosity. Is.

The porous cross-linked copolymer produced by such a method may be subjected to sulfonation or chlormethylation by a known method in some cases, and then the aminated ion exchange resin may have the above-mentioned porous copolymer weight. It is preferable as well as coalescence. These porous spherical cross-linked copolymers may be commercially available products. For example, Amberlite's ion exchange resin series or synthetic adsorbent series may be used, and many commercially available products such as Diaion (registered trademark of Mitsubishi Kasei Co., Ltd.) and Dowex (registered trademark of Dow Chemical Co.) can be used. Of course.

A desired adsorbent is produced by carbonizing the porous spherical crosslinked copolymer thus obtained by a known method.

This porous spherical crosslinked polymer is infusibilized with sulfuric acid, nitrogen dioxide, chlorine or the like and pyrolyzed at a temperature of 300 to 900 ° C. to obtain a desired carbonaceous adsorbent. The adsorbent thus obtained can be used as it is, but if desired, it can be used after being sufficiently activated by steam, an aqueous solution of zinc chloride or the like.

Ambersorb XE series manufactured by Rohm and Haas Company is known as a specific example of such an adsorbent. This adsorbent is spherical and has a low ash content, and is characterized by high abrasion resistance and physical strength. These secondary characteristics have special significance for the treatment of endotoxin in pure water.

In addition to the effective adsorbability of endotoxin by the adsorbent, these characteristics make it possible to treat endotoxin in pure water without deteriorating the water quality.

In other words, normal activated carbon for water treatment not only serves as a hotbed for the growth of bacteria due to its irregular shape, but also crushes due to its weak physical strength and abrasion resistance and remains as fine particles in the treatment system, deteriorating the water quality. And other troubles. The biggest difference between this adsorbent and commercially available powder or granular activated carbon is that its physical structure is fundamentally different from that of activated carbon, and the skeleton structure of the porous spherical polymer is still retained after carbonization and activation. Is. It is considered that this difference contributes to a large difference in the adsorption amount for endotoxin.

In the production of ultrapure water or ultrapure water, deionized water containing endotoxin from the ion exchange resin treatment process is stored in a water tank, an ultraviolet sterilizer, a regenerative mixed bed ion exchange resin tower, and an ultrafiltration membrane. Alternatively, a series of treatment steps using a permeable membrane such as a reverse osmosis membrane are allowed to pass, but the adsorption step using the carbonaceous adsorbent is placed at an arbitrary position between the water storage tank and the permeable membrane. In the case of ultrapure water for medical use such as water for injection that does not contain pyrogens, or ultrapure water required for the production of semiconductors due to the recent high integration of semiconductor elements, the viable cell count of the endotoxin source is 0.02. It demands a strict level of less than 1 / ml. In such ultrapure water or ultrapure water production, live bacteria are sterilized by ultraviolet light, but endotoxin is released into water from dead bacteria. It is preferable that the endotoxin removal treatment of the present invention is carried out before the treatment with, or the endotoxin removal treatment of the present invention is carried out before the final permeable membrane treatment. By doing so, it is possible to efficiently produce ultrapure water or ultrapure water that does not contain endotoxin. This carbonaceous adsorbent is packed in a column of an appropriate size and the water to be treated is passed through it. Can be used to adsorb endotoxin.

〔The invention's effect〕

According to the present invention, endotoxin-free ultrapure water can be stably produced in a large amount by an extremely simple method.

〔Example〕

 Hereinafter, the present invention will be specifically described with reference to examples.

Reference Example 1. Using tap water as raw water, deionized water production consisting of a granular activated carbon tower, a gel type cation exchange resin tower, a gel type anion exchange resin tower, and then an ion exchange resin tower made of a mixed bed type porous spherical crosslinked polymer When the device was operated intermittently at room temperature (about 20 ° C) for about 4 hours at a water intake of about 100 liters, endotoxin leaked into deionized water at an average level of 1.5 ng / ml after about 2 weeks.

Therefore, both gel-type cation and anion exchange resins were regenerated by a conventional method and water flow was restarted, but from the second day, endotoxin leaked to the above-mentioned level in deionized water.

When the cause was investigated, it was found that the granular activated carbon bed of the activated carbon tower was a hotbed for bacterial growth. Therefore, the treated water pipe was divided into three pipes so that the same amount of water would flow, and the first pipe was packed with 300 g of Ambersorb 347, and the second pipe was 300 g of Calgon's Pittsburgh granular activated carbon column. To the third pipe for comparison, 300 g of Amberlite XA, a non-carbonized porous spherical cross-linked polymer
D-2 was attached and water flow was started.

The treatment amount at the detection limit of endotoxin of 0.01 ng / ml was as follows.

Reference Example 2 Using tap water as raw water, a deionized water production apparatus comprising a granular activated carbon tower, a gel type cation exchange resin tower, a gel type anion exchange resin tower, and then an ion exchange resin tower made of a mixed bed type porous spherical crosslinked polymer After intermittent operation at room temperature (about 20 ° C) for about 4 hours with a water intake of about 100 l, endotoxin leaked to the deionized water at an average level of 1.5 ng / ml after about 2 hours.

Then, the treated water pipe was divided into three pipes so that an equal amount of water could flow, and the first pipe had 100 g of Amber Soap XE-3.
The column packed with 47 was carbonized with 50 g of the carbonaceous adsorbent obtained by carbonizing the synthetic adsorbent shown below in the second pipe, and the column packed with 50 g of the activated carbonaceous adsorbent was packed into the third pipe. For comparison, a column filled with 100 g of a non-carbonized porous synthetic polymer was connected to the pipe to start water passage at the same time.

The treatment amount at the detection limit of 0.01 ng / ml of endotoxin is as follows.

Treatment amount (l) (1) Ambersorb XE-347 1250 (2) Carbon adsorbent (carbonization + carbonization-activation) 1180 (3) Porous synthetic polymer 580 The method for producing the carbonaceous adsorbent is as follows. Is. Polyvinyl alcohol 5.0g, Carboxymethyl cellulose
2g, Nacl 56g was dissolved in distilled water 1.5l, and a mixture of styrene 200g, divinylbenzene (purity 59%) 132g, butanol 240g, benzoyl peroxide 1.5g was added and stirred at 85 ° C.
And reacted for 6 hours to obtain a porous synthetic polymer (3).

Next, 250 g of this porous cross-linked copolymer was added to 15% fuming sulfuric acid 31%.
The sulfonation reaction was carried out in 00 g at 110 ° C. for 6 hours, washed with sulfuric acid, washed with water and dried. 300 ℃ / hr in nitrogen stream
The carbonaceous adsorbent (2) having an apparent specific gravity of 0.5 g / cc and a pore volume of 0.6 g / cc was obtained by calcination at 950 ° C. Next, a part thereof was activated at 800 ° C. for 2 hours in a steam atmosphere to obtain a carbonaceous adsorbent (2) having a surface area of 1100 m ² / g.

Example 1 Deionized water treated with tap water as raw water and treated with a granular activated carbon tower, a gel type cation exchange resin tower, an anion exchange resin tower, and an ion exchange resin tower composed of a mixed bed type porous spherical crosslinked polymer 20
Put it in a 0 l water tank (the deionized water production device on the raw water side will automatically operate so that it can always maintain 200 l), and then sterilize the ultraviolet rays, the regenerative mixed bed type ion exchange resin tower, the ultra-permeation membrane and the point of use (faucet). ) And unused water is returned to the water tank.
About 100l per day Purity 18.2MΩ · cm) One week after the start, water was collected from the sampling point between the regenerative mixed bed ion exchange resin tower and the ultrafiltration membrane and analyzed, and endotoxin was 0.5ng / ml. Were present.

Therefore, when a column filled with 500 g of Amberthorpe XE-340 was placed after the UV sterilizer, the endotoxin level in the system was below the detection limit (0.01 ng / ml) even after passing water for 9 days. Kureha Chemical Co., Ltd. spherical activated carbon BAC-MP
In the case of, the endotoxin leak started in 4 days.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-53-50088 (JP, A) "Proceedings of the 54th Annual Meeting of the Chemical Society of Japan 54" (62.3.12.) The Chemical Society of Japan No. 525 Top of page

Claims (1)

[Claims] 1. A deionized water containing endotoxin from an ion exchange resin treatment step is received in a water storage tank, followed by ultraviolet sterilization, treatment with a regenerative mixed bed ion exchange resin and a membrane with an ultrafiltration membrane or a reverse osmosis membrane. In the method for producing ultrapure water that passes through a series of steps of treatment, a carbonaceous adsorbent obtained by carbonizing a porous spherical crosslinked polymer or a carbonaceous adsorbent activated by carbonization and having a porous spherical crosslinked polymer A method for removing endotoxin in ultrapure water, which comprises placing an adsorption step using a carbonaceous adsorbent having a skeletal structure as it is after the water storage tank but before the membrane treatment step.