JP2002035112A - Method for removing endotoxin from dialysate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prevent various kinds of harmful influences resulting from the movement of the endotoxines contained in a dialysate used for artificial hemodialysis to the blood by removing the endotoxines contained in the dialysate. SOLUTION: At least part of a dialysate supply line from a dialysate preparing device for artificial hemodialysis to a dialyzer with a wash prepared by dissolving a water-soluble reducer composed mainly of a dithionite of 0.1-3 pts.wt. and at least one kind of pH buffer selected from among hydroxy- carboxylic compounds, carboxylic compounds, amino-carboxylic compounds, phosphate compounds, organic phosphate compounds, and carbonate compounds of 0.05-5 pts.wt. in water of 100 pts.wt.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for removing endotoxin in a dialysate used for artificial hemodialysis, and more particularly to a dialysate supply line from a dialysate preparation device to a dialyzer, and a reverse line for producing a dialysate dilution water. The present invention relates to a method for removing endotoxin by washing a water supply line from the inside of a permeable membrane device to a dialysate preparation device.

[0002]

_2. Description of the Related Art In recent years, in artificial hemodialysis, in order to prevent dialysis amyloid complications due to β ₂ -microglobulin (molecular weight 11800) which accumulates in blood with prolonged treatment, a cellulose triacetate membrane or the like is used. High-performance dialyzers using high-performance dialysis membranes having a large pore size are rapidly spreading. However, such a high-performance dialyzer has excellent removal efficiency of macromolecules including β ₂ -microglobulin in blood, but there is a concern that harmful substances on the dialysate side may migrate into blood by reverse osmosis or reverse diffusion. is there. This harmful substance is endotoxin (bacterial endotoxin) derived mainly from Gram-negative bacteria that contaminates the dilution water of the dialysate, causing fever, various allergic symptoms, and various complications due to promotion of cytokine production. It has been pointed out that this may be the cause of the disease.

Therefore, as a countermeasure, an endotoxin cut filter (hereinafter abbreviated as ETCF) is interposed in the middle of the dialysate supply line to filter and remove endotoxin in the dialysate before entering the dialyzer. Has been adopted. However, this ETCF
Does not completely remove endotoxin, but only reduces its concentration. Therefore, in order to eliminate various adverse effects caused by endotoxin, it is necessary to keep the dialysate itself clean.

At present, dialysate dilution water is obtained by removing mainly cations from tap water, which is raw water, using an ion exchange resin, and then removing chlorine and organic substances using activated carbon.
Reverse osmosis membrane filtered water (hereinafter abbreviated as RO water) which has been subjected to a treatment to remove other than water molecules by a reverse osmosis membrane device is used. However, RO water should not contain anything other than water molecules, but a large amount of endotoxin is actually measured. This is because in the reverse osmosis membrane device, substances that could not be removed by the previous treatment with ion-exchange resin or activated carbon accumulate on the membrane surface, causing the filtration ability to decrease over time. This is presumably due to the fact that the water passage including the reverse osmosis membrane device is in an environment vulnerable to bacterial contamination because the water is removed in advance.

Conventionally, as a means for removing bacterial contamination in a reverse osmosis membrane device, disinfection with formalin or the like has been performed. However, the measurement results of the endotoxin level of the RO water show that such disinfection does not easily remove bacterial contamination. In the reverse osmosis membrane device, even if the bacteria themselves are not filtered, even if a very small part of the cells is filtered or leaked, the dilution water is contaminated as endotoxin.

On the other hand, a dialysate is prepared by diluting a dialysate with the RO water in a dialysate preparation device, and is usually sent from a central supply device to a dialyzer via a microfilter, a patient monitoring device, and an ETCF. After performing blood purification in the above, the waste liquid is again passed through the patient monitoring device. For the dialysis line, a medical silicone tube having a transparent feeling is mainly used. Conventionally, dialysis lines have been generally used to remove organic substances and disinfect by disinfecting and rinsing with a disinfecting solution containing sodium hypochlorite after completion of dialysis, and then periodically perform acetic acid. To remove accumulated calcium carbonate.

However, when the endotoxin value of the water sampled at the position immediately before the dialyzer after the disinfection cleaning is measured, the endotoxin value of the original RO water is always higher than that of the original RO water. This is because conventional disinfection cleaning with sodium hypochlorite and acetic acid cleaning cannot maintain sufficient cleanliness of the dialysis line, not only reducing endotoxin, but also accumulating additional endotoxin and new contamination in the dialysis line. Suggests that it may have occurred.

[0008]

In view of the above circumstances, the present inventor has taken drastic measures different from the conventional disinfecting washing and the like in order to keep the dialysate itself clean and eliminate the harm caused by endotoxin. In view of the necessity of taking measures, the study on endotoxin decontamination means was repeated from various angles. In the course of this study, the piping of the dialysate supply line from the dialysate preparation device to the dialyzer,
Focusing on the fact that the silicon tubing used in the water supply line piping from the reverse osmosis membrane device that produces the dialysate dilution water to the dialysate preparation device is generally colored brown, and analyzed the causes did.

As a result, the coloring is mainly due to the rust-like iron (which is considered to be iron oxide) adhering to the inner surface of the tube, and a fine substance containing endotoxin may be entrapped and deposited on the iron. In addition to its high potential, it was also found that there was a suspicion that bacteria were proliferating in the sedimentary layer, protected from disinfection with sodium hypochlorite or the like. In addition, in the dialysis line, the silicon tube in the supply line is clearly darker than the silicon tube in the waste liquid line after the dialyzer, and the iron content actually detected is larger in the former tube. Sometimes it is speculated that iron adhering to the inner wall of the supply line is released and moves to the blood side through the dialyzer, and naturally endotoxin etc. entrapped together with the iron is also released and moves to the blood side Is done.

[0010] The above-mentioned iron may be contained in the dialysate supply line due to corrosion of the metal part by sodium hypochlorite used for disinfection cleaning. RO not in contact with sodium
Since coloring is also seen in the water tank and the silicon tube of the water supply line, it is considered that the coloring is mainly derived from the RO water itself. The fact that the main component of the coloring of the silicon tube is iron is that the coloring surface has a colorless surface due to the iron removal agent Dirachemi M-10 (containing ammonium thioglycolate: 0.0005 μg or more of iron). (Changed to purple) was confirmed by color change when dropped.

Based on the above findings, the present inventor has proposed, as a method for removing endotoxin from a dialysate, a dialysate supply line from a dialysate preparation device to a dialyzer, and a reverse osmosis membrane device for producing a dialysate dilution water. Investigations were made on the possibility of a revolutionary means of simultaneously removing contaminants such as endotoxin entrapped in the iron by removing the iron attached to the water supply line from the inside to the dialysate preparation device. The reverse osmosis membrane device has been conventionally subjected to iron removal treatment with an aqueous solution of oxalic acid or citric acid. By using these aqueous solutions, an RO water tank, a silicon tube, an ETCF, a water removal pump unit (patient) is actually used. Even if the inner surface of the device made of synthetic resin (such as in the monitoring device) is washed, the coloring cannot be removed, and even if the formalin treatment is further performed after the iron removal treatment in the reverse osmosis membrane device, the endotoxin value may be reduced. It has also been confirmed that they do not decrease sufficiently, and these results suggest that iron removal treatment with an aqueous solution of oxalic acid or citric acid is ineffective as a means of removing endotoxin.

[0012]

As a result of the study by the present inventor, if the dialysate supply line and the dilution water supply line are washed with a washing solution containing a specific water-soluble reducing agent, the silicone tube can be used. It is used for subsequent dialysis because the iron that has adhered and accumulated in the line, including the inner surface of the equipment made of synthetic resin, etc., is removed neatly, and at the same time, minute substances such as endotoxin embraced by the iron are also removed. It was found that the dialysate to be purified contained almost no endotoxin, and it was found that various adverse effects due to the transfer of endotoxin to the blood side could be reliably eliminated, and the present invention was achieved.

That is, the method for removing endotoxin from a dialysate according to claim 1 of the present invention is based on 100 parts by weight of water.
Water-soluble reducing agent containing dithionite as a main component 0.1 to 4
Parts by weight and b) 0.05 to 6 parts by weight of at least one PH buffer selected from a hydroxycarboxylic acid compound, a carboxylic acid compound, an aminocarboxylic acid compound, a phosphoric acid compound, an organic phosphonic acid compound and a carbonate compound. And
It is characterized in that at least a part of a dialysate supply line from a dialysate preparation device in artificial blood dialysis to a dialyzer is washed with a washing solution having an initial PH of 6.0 to 8.0.

According to a second aspect of the present invention, there is provided a method for removing endotoxin from a dialysate, wherein the washing solution according to the first aspect is used for dialysis from within a reverse osmosis membrane device for producing a dilution of the dialysate in artificial hemodialysis. The present invention is characterized in that at least a part of a water supply line leading to a liquid producing apparatus is washed.

Further, in the method for removing endotoxin from a dialysate of a washing solution according to the present invention, the water-soluble reducing agent of the washing solution is 60 to 100% by weight of dithionite, sulfite, bisulfite, pyrosulfite. And Rongalit, thiourea dioxide, thioglycolic acid and a salt thereof, ascorbic acid and a salt thereof, and a reducing agent component selected from erythrobic acid and a salt thereof in an amount of 0 to 40% by weight. The initial pH is 6.0 to 7.5, and the pH after one hour of residence in the line to be cleaned is 6.0 to 7.5.
The configuration according to claim 4 which is set so as to be in the range of 7.0 is a preferable mode.

[0016]

DETAILED DESCRIPTION OF THE INVENTION In the method for removing endotoxin from a dialysate according to the present invention, dialysis from a dialysate preparation device to a dialyzer in an artificial hemodialysis is performed by a washing solution containing a water-soluble reducing agent containing dithionite as a main component. At least a part of a liquid supply line and / or a water supply line from a reverse osmosis membrane device for producing a dialysate dilution water to a dialysate preparation device is washed. As a result, the rust-like iron that has adhered and accumulated on the inner surface of each device constituting the dialysate supply line or the water supply line is removed, and the endotoxin contained in the adhesion accumulation layer along with the removal of the iron is removed. It has also been found that micro-substances such as can be removed and the dialysate used in the subsequent dialysis can be cleaned. In other words, endotoxin that has adhered to the inner surface of the equipment and could not be removed by conventional disinfection cleaning or acetic acid cleaning is released into the cleaning solution by removing iron, and is discharged and removed together with the cleaning solution.

Incidentally, a water-soluble reducing agent or an acidic substance is considered to be effective for removing iron rust attached to a metal surface. Examples of the water-soluble reducing agent include, in addition to the dithionite used in the present invention, sulfite, bisulfite, pyrosulfite, thiosulfate, Rongalite, thiourea dioxide, ascorbate, erythrobic acid Representative examples include salts and thioglycolates. Also, as the acidic substance, oxalic acid, citric acid, sulfamic acid and the like are said to be effective in removing iron rust. However, with water-soluble reducing agents other than dithionite and the above-mentioned acidic substances, rust-like substances adhered to the surface of a synthetic resin such as a silicon tube used for piping of a dialysate supply line or a dilution water supply line. It has been found that iron cannot be removed. Next, the iron removal test of the silicon tube with these water-soluble reducing agents and acidic substances and the results are shown.

[Silicon Tube Iron Removal Test] A brown colored silicon tube of a dialysate supply line used in an artificial dialysis facility was used as a sample, and an aqueous solution of each component described in Table 1 below was injected into the tube. The removal of iron was confirmed by the disappearance of the brown coloration. ○: Removed within 2 hours staying in the tube, ○: Removed within 2 hours and 6 hours , And the case where it was not removed even in the same 24 hours is shown in Table 1 as x. In addition, about a water-soluble reducing agent component, 1% aqueous solution was used,
A 5% (weight / volume) aqueous solution of phosphoric acid as an acidifying agent and a 5% (weight / volume) aqueous solution of sodium hydroxide as an alkalizing agent are added thereto to adjust the pH so that the acidity (PH4 ± 0.2) is obtained. ), Neutral (PH 6.5 ± 0.3) and alkaline (PH 9.1 ± 0.2) three aqueous solutions are prepared (when the initial PH of the 1% aqueous solution itself corresponds to any of the three types, (Use without pH adjustment as aqueous solution of applicable species)
Then, a test using each aqueous solution was performed. For the acidic substances oxalic acid and citric acid, a test was performed using a 1% aqueous solution and an aqueous solution in which ammonia was added to slightly increase the pH.

[0019]

[Table 1]

As is clear from Table 1, iron attached to the inner surface of the silicon tube can be removed within 6 hours only by a neutral to alkaline aqueous solution of sodium dithionite. Agents and acidic substances cannot be removed for as long as 24 hours. The equipment constituting the dialysate supply line and the dialysate dilution water supply line in artificial hemodialysis includes the above-mentioned silicon tube, RO water tank, membrane of reverse osmosis membrane device, dialysate preparation. The liquid contact surface is often made of synthetic resin, such as a mixing chamber in the device, a microfiltration device, an ETCF, and a water removal pump in a patient monitoring device. This suggests that even if the washing is performed, the effect of removing iron by endotoxin can hardly be expected.

The cleaning solution used in the present invention contains dithionite as an essential component as described above, but contains this dithionite as a main component and another water-soluble reducing agent as an auxiliary component. It may be included. Examples of the water-soluble reducing agent of such an auxiliary component include sulfites, bisulfites, pyrosulfites, Rongalite, thiourea dioxide, thioglycolic acid and its salts, ascorbic acid and its salts, erythrobic acid and its salts, and the like. Can be used. However, the dithionite as the main component desirably accounts for 60% by weight or more of the total amount of the water-soluble reducing agent in order to sufficiently exert the endotoxin removing effect of iron removal. Therefore, a preferred washing liquid used in the present invention is such that the water-soluble reducing agent is 60 to 100% by weight of dithionite and the other reducing agent components are 0 to 40%.
% By weight.

However, a problem in iron removal using dithionite is generation of toxic sulfurous acid (SO ₂ ) gas due to decomposition of dithionite. The decomposability of this dithionite varies greatly depending on the pH of the aqueous solution, and is strong in an acidic region and weak in an alkaline region. Incidentally, Table 2 below shows test results obtained by examining the relationship between the pH of the aqueous solution of sodium dithionite and the amount of generated sulfurous acid gas. In this test, 500 ml of a buffer adjusted with a 5% (weight / volume) aqueous solution of phosphoric acid and a 5% (weight / volume) aqueous solution of sodium hydroxide was placed in a 1 L beaker. After dissolving 5 g of sodium thionate and immediately measuring the pH, the beaker was sealed, and after one hour, the concentration of sulfur dioxide in the beaker was measured with a detector tube.

[0023]

[Table 2]

According to Table 2, the amount of sulfur dioxide gas generated from the aqueous solution of sodium dithionite was 500 ppm at PH 5.6.
On the other hand, in the case of the same PH6.1, it is only 20 ppm, and it can be seen that the pH increases extremely rapidly toward the acidic side around the vicinity of PH6. Therefore, in order to carry out the washing operation safely, the detergent containing dithionite has an initial pH of 6.0.
It is necessary to set above.

Further, in iron removal using an aqueous solution of dithionite, the pH of the aqueous solution decreases with the progress of the reduction reaction. Occurrence becomes remarkable, which also causes a problem in work safety. In addition, in the aqueous solution of dithionite alone, a phenomenon has been observed in which the insoluble sulfur compound precipitates gradually and the liquid becomes cloudy, and the formation of this precipitate and suspended matter is for the purpose of purifying the dialysis line. It is a thing to dislike. Therefore, in the cleaning solution used in the present invention, a hydroxycarboxylic acid compound, a carboxylic acid compound, an aminocarboxylic acid compound, a phosphoric acid compound, an organic phosphonic acid compound, together with a water-soluble reducing agent containing dithionite as a main component. At least one PH buffer selected from carbonate compounds is dissolved.

That is, by using this PH buffer,
A decrease in the pH of the cleaning solution (aqueous solution) accompanying the progress of the reduction reaction is suppressed, and thus the generation of sulfurous acid gas is remarkably reduced. However, the iron elimination property is improved, and the white turbidity phenomenon can be prevented. It is known.

Here, as specific examples of the above-mentioned PH buffer, there are alkali metal salts and ammonium salts such as lactic acid, glycolic acid, malic acid, tartaric acid, citric acid and gluconic acid for hydroxycarboxylic acid compounds and carboxylic acid compounds. Alkali metal salts and ammonium salts such as formic acid, acetic acid, oxalic acid, succinic acid, maleic acid and fumaric acid, and alkali metal salts and ammonium salts such as nitrilotriacetic acid (NTA) and ethylenediaminetetraacetic acid (EDTA) for aminocarboxylic acid compounds , Phosphate compounds, phosphoric acid, pyrophosphate,
Alkali metal salts and ammonium salts such as tripolyphosphoric acid, tetraphosphoric acid, and hexametaphosphoric acid, and 2-phosphone-butane-tricarboxylic acid 1 in organic phosphonic acid compounds.
Examples thereof include alkali metal salts and ammonium salts such as 2,4,1-hydroxyethylidene-1,1-diphosphonic acid, aminotri (methylenephosphonic acid), ethylenediamine (tetraphosphonic acid), and diethylenetriaminopentane (methylenephosphonic acid). Examples of the carbonate compound include an alkali metal salt and an ammonium salt in carbonate, hydrogen carbonate, sesquicarbonate and the like.

The amount of the water-soluble reducing agent and the pH buffer in the washing solution is 0.1 to 4 parts by weight for the water-soluble reducing agent and 0.05 to 6 parts by weight for the PH buffer per 100 parts by weight of water. I do. That is, the amount of the water-soluble reducing agent is 100
If the amount is less than 0.1 part by weight with respect to part by weight, the iron removing action and, consequently, the endotoxin removing action accompanying iron removing will be insufficient,
Conversely, if the amount exceeds 4 parts by weight, no further improvement in the iron removal action is recognized, dissolving becomes difficult, and there is a problem in wastewater treatment (the reducing agent is counted as iodine consumption in the wastewater). growing. The pH buffering agent has a strong or weak pH buffering action depending on the type of compound used.
If the amount is less than 0.05 part by weight with respect to 0 part by weight, a sufficient PH buffering effect cannot be obtained, and if it exceeds 6 parts by weight, there is a problem that the dissolution is difficult and the BOD and COD of the wastewater also increase. In addition, it is uneconomical because the effect corresponding to the amount cannot be expected.

Next, with respect to the cleaning liquids prepared with various compositions, the time-dependent changes in PH, the time-dependent changes in the amount of generated sulfurous gas, and the iron removal properties when applied to the cleaning of silicon tubes were examined. The amounts are shown in Tables 3 to 6 together with the amounts (parts by weight based on 100 parts by weight of water). In addition, Na attached to the name of each component in these tables is sodium, and K is potassium. The symbols () in these tables mean that no measurement was made. Thus, as for the silicon tube, the brown color of the dialysate supply line used in the artificial dialysis facility is used as a sample as described above, and each washing solution is injected into the tube to fill the tube, and the brown color disappears. This confirmed the removal of iron. The iron elimination property was evaluated on the following five levels. ◎ ・ ・ ・ Brown completely disappears.・ ・ ・: Slight brown color is recognized. □ ・ ・ ・ A little brown remains. Δ: fairly brown remains ×: little change from original brown

[0030]

[Table 3]

[0031]

[Table 4]

[0032]

[Table 5]

[0033]

[Table 6]

From Tables 3 to 6, the following is clear. First, in the cleaning solution (No. 1 and 2) in which only a water-soluble reducing agent, disulfite, was dissolved, although the iron removal property was good, the PH rapidly decreased in a short time and a large amount of sulfurous acid gas was released. Therefore, there is a problem in the safety of the cleaning operation. On the other hand, in the cleaning solution (No. 3-36) in which the PH buffer was added together with the dithionite, although there was a difference depending on the type and the amount of the PH buffer used, the pH over time was due to the PH buffer action. Since the decrease is suppressed, the generation of sulfurous acid gas is reduced. However, the cleaning solution (No. 4, 5) whose initial PH is set higher than 8.0 can prevent the generation of sulfurous acid gas, but cannot exert the iron-removing property and cannot expect the action of removing endotoxin accompanying iron-removing. . Therefore, the initial pH of the cleaning liquid needs to be in the range of 6.0 to 8.0.

Meanwhile, at the site of a medical facility where artificial hemodialysis is performed, it is difficult to suspend the dialysis apparatus for a long time, and there are restrictions on the personnel and labor involved in the cleaning operation, and the cleaning operation of the line is completed in as short a time as possible. It is necessary. In this regard, the initial pH is adjusted to 6.0 by adding a pH buffer.
The cleaning solution (Nos. 9 to 36) set to ~ 7.5 can remove iron in a short time of 4 hours or less, and thus can sufficiently meet the above requirements. However, with the cleaning solution (No. 6 to 8) in which the initial PH is 8.0 or less and higher than 7.5, iron removal cannot be performed in a short time, but after 24 hours, iron removal can be sufficiently performed. For example, if an opportunity to suspend the dialysis line on a medical institution holiday or the like can be used, it becomes useful for endotoxin removal and cleaning.

Note that even if a pH buffer was added, the cleaning solution (No. 10, No. 10) in which the pH after one hour of retention was lower than 6.0.
In 16), the generation of sulfurous acid gas cannot be sufficiently suppressed. In addition, it has been found that when the pH after one hour of residence exceeds 7.0, the iron-removing property decreases, and the endotoxin removing action also decreases accordingly. Therefore, in order to obtain a cleaning liquid that enables rapid iron removal and sufficiently suppresses the generation of sulfurous acid gas, the initial PH is in the range of 6.0 to 7.5, and the pH after one hour of retention is 6.0. It is most desirable to set it so that it is in the range of 0 to 7.0. It should be noted that the pH one hour after the retention can be easily known empirically from the amount of the dithionite and the type and amount of the PH buffer.

On the other hand, when other water-soluble reducing agent components were blended together with dithionite as a main component as a water-soluble reducing agent, As is clear from the comparison between the 28-35 cleaning solution and the other cleaning solutions, the progress of iron removal tends to be slower than the cleaning solution using dithionite alone as the water-soluble reducing agent. Therefore, even though these other water-soluble reducing agent components can be used as accessory components, no particular effect can be obtained by using them.

As described above, the method for removing endotoxin from a dialysate according to the present invention uses at least a part of the dialysate supply line from the dialysate preparation device to the dialyzer in artificial hemodialysis, This is to wash at least a part of a water supply line from a reverse osmosis membrane device for producing dialysate dilution water in dialysis to a dialysate preparation device. In the latter cleaning of the water supply line,
Since the RO water is cleaned by removing endotoxin accompanying iron removal, endotoxin in a dialysate using the RO water as dilution water is reduced. The washing may be performed not only by passing the liquid through the entire line, but also at every fixed section of the line, or may be performed in units of equipment such as devices interposed in the line and detached silicon tubes. In the dialysis fluid supply line, the dialysis fluid supply line includes a dialysis fluid preparation device, a central supply device, a microfilter, a patient monitoring device, an ETCF, and the like. In the water supply line,
There are reverse osmosis membrane devices and RO water tanks.

[0039]

EXAMPLES Examples of the method for removing endotoxin from a dialysis solution according to the present invention will be specifically described below.

Example 1 15 parts by weight of sodium citrate and 1.5 parts by weight of sodium carbonate were dissolved in 100 parts by weight of water, and 16.5 parts by weight of sodium dithionite was further dissolved in this aqueous solution. Prepared. The washing stock solution is diluted 35 times with RO water in a central supply device (DAB-C manufactured by Nikkiso Co., Ltd.) of a dialysate supply line to make a washing solution, and the washing solution is converted into the central supply device → a microfiltration device (EK100 manufactured by Asahi Emers Co., Ltd.). −
B) → Patient monitoring device (DS-22B manufactured by Nikkiso Co., Ltd.) → E
TCF (Nikkiso Co., Ltd. EF-01) → Patient monitoring device → Liquid is sent to the dialysate supply line connected by a silicon tube that becomes waste liquid for 15 minutes, and is retained for 2 hours and then washed with water (2 hours). Iron removal cleaning was performed. The cleaning solution had an initial pH of 6.9 after dilution, and a pH of 1 hour after retention.
H was 6.3.

Thus, a mixing tank (stainless steel) and a silicon tube in a central feeder, a microfilter, a bubble separation chamber (glass and polypropylene) in a patient monitor and a housing of a dewatering pump (stainless steel), an ETCF Each of the silicon tubes in the piping was colored brown, but after the above-described iron removal cleaning, the brown completely disappeared and the original color was restored. Also, the brown particles in the microfilter and the ETCF housing disappeared after the iron removal washing. During the iron removal cleaning, there was no smell of sulfurous acid gas in the machine room having the central supply device and the dialysis treatment room having the patient monitoring device, and no sulfurous acid gas was detected by the gas detection tube. Further, it was confirmed that the water subjected to the water washing did not finally contain the washing liquid component by detecting the reducing agent component using the iodine solution and observing changes in the amount of sodium and the conductivity.

On the other hand, in the dialysate supply line before performing the iron removal cleaning, the number of fine particles in the dialysate at the entrance and exit of the central supply device and the ETCF outlet was measured by a fine particle meter (MILPA-PR manufactured by Mikuni Kikai). , ETCF
The endotoxin level in the dialysate at the outlet was measured by the endospace method. In addition, the dialysis solution supply line after the iron removal cleaning was subjected to normal disinfection cleaning with sodium hypochlorite, and then subjected to normal artificial dialysis treatment for 3 days. The number of microparticles in the dialysate at the ETCF outlet and endotoxin were measured. As a result, as shown in the following Table 7, the iron removal cleaning significantly reduced the number of fine particles at the outlet of the central feeder and at the ETCF outlet, and did not detect endotoxin at the ETCF outlet. Note that the above disinfecting cleaning is usually performed after the completion of each dialysis with sodium hypochlorite 10 times.
After the 00 ppm aqueous solution is sent to the line for 30 minutes, it is washed with water. Also, the line is acid-washed twice a week by a method in which a 1% aqueous solution of acetic acid is fed for 30 minutes and washed with water before the disinfecting washing. Washing was performed.

[0043]

[Table 7]

Example 2 8 parts by weight of dipotassium hydrogen phosphate in 100 parts by weight of water and ED
6 parts by weight of TA · 2Na and 1.5 parts by weight of sodium carbonate were dissolved, and 16 parts by weight of sodium dithionite were further dissolved in this aqueous solution to prepare a stock solution for washing. This washing stock solution is supplied to the central supply unit (Nipro N
CS-400N), dilute 50-fold with RO water to obtain a washing solution, and apply this washing solution to the central supply device →→ Patient monitoring device (Nipro NCU-5) → ETCF (Nipro CF-6009) → Patient monitoring Iron removal was carried out by feeding for 15 minutes to a dialysate supply line connected by a silicon tube which becomes a waste liquid from the apparatus and retaining for 2 hours, followed by washing with water (2 hours). In addition, this washing liquid had an initial pH of 6.6 after dilution and a pH of 6.4 after one hour of residence.

The mixing chamber (stainless steel) and silicon tube in the central feeding device, the silicon tube in the patient monitoring device and the housing of the dewatering pump (stainless steel), the ETCF, and the silicon tube in the piping are all brown. However, the brown color had completely disappeared and the original color had been restored after the iron removal washing. During the iron removal cleaning, there was no smell of sulfurous acid gas in the machine room having the central supply device and the dialysis treatment room having the patient monitoring device, and no sulfurous acid gas was detected by the gas detection tube. Further, it was confirmed that the water subjected to the water washing did not finally contain the washing liquid component in the same manner as in Example 1.

On the other hand, in the dialysate supply line before the iron removal washing, the dialysate was sent to the ETCF outlet, and the dialysate was collected and the endotoxin value was measured as in Example 1. 9 (EU / L). However, after the above-described iron-removal cleaning, normal disinfection cleaning with sodium hypochlorite is performed, and before the preparation for artificial dialysis treatment on the next day, the dialysate is sent to the ETCF outlet, and the RO water is collected and the endotoxin is collected. When the values were measured in the same manner, endotoxin in the collected water was not detected. In this dialysate supply line, an 800 ppm aqueous solution of sodium hypochlorite was sent to the line for 30 minutes after the completion of each dialysis as the disinfecting cleaning, and water washing was performed.
A 1% aqueous solution of acetic acid was sent for 30 minutes at a time to wash with water.

The cleaning liquid used in Examples 1 and 2 was repeatedly immersed in the liquid for 20 hours seven times to examine the effects of synthetic resins, rubbers, and metals on various materials. As a result, any resin such as fluororesin, polypropylene, polyethylene, acrylic resin, polystyrene, polyamide, polycarbonate, synthetic resin such as polyvinyl chloride, butadiene rubber, silicone rubber, natural rubber, rutile rubber, etc. No dimensional or weight changes were observed. As a result, it was found that the cleaning solution used in the present invention did not adversely affect various devices constituting the dialysis line, and could be used for endotoxin removal with confidence.

Example 3 In a synthetic resin RO water tank, with respect to 100 parts by weight of water,
A washing solution is prepared by dissolving 0.5 part by weight of sodium citrate and 0.5 part by weight of sodium dithionite, and a reverse osmosis membrane device (MP-Miknikikai Co., Ltd. By the operation of α) for 3 minutes, the cleaning liquid was filled in the module of the apparatus and allowed to stay for 100 minutes, and then water washing was performed until the conductivity was reduced to a constant level, and the iron removal cleaning was completed. This cleaning solution had an initial pH of 6.4 after dilution and a pH of 6.3 after 1 hour of residence.
Although the inside of the RO water tank was colored brown, the brown color disappeared due to the cleaning liquid. Next, the RO water was drained by the reverse osmosis membrane device for another 30 minutes, and then the RO water sampling operation was performed. The results obtained by measuring the number of fine particles and the endotoxin value in the same manner as in Example 1 for the RO water after the operation for 2 hours (after the iron removal cleaning) and the RO water before the iron removal cleaning are shown in Table 8 below. Table 8 also shows the operation status before and after the iron removal cleaning and at the time of introducing the apparatus (new equipment).

[0049]

[Table 8]

As is clear from Table 8, the number of fine particles in the RO water and the endotoxin value were remarkably reduced by the iron removal washing, and the number of fine particles and the endotoxin value of the dialysate using this as the dilution water were naturally reduced. You can see that.
Also, in the operation of the reverse osmosis membrane device, the operating pressure is reduced and the conductivity is also reduced by the iron removal treatment, suggesting that the filtration state close to the time of introduction of the device is restored.

[0051]

According to the method for removing endotoxin from a dialysate according to the first aspect of the present invention, at least a dialysate supply line from a dialysate preparation device to a dialyzer in artificial hemodialysis is provided by a specific washing solution having an iron-removing action. Since part of the line is washed, the rust-like iron that has adhered and accumulated on the inner surface of each device constituting the line is removed, and minute substances such as endotoxin contained in the adhered accumulation layer are also removed. In other words, endotoxin that could not be removed by conventional disinfection washing or acid washing can be efficiently removed, making the dialysate clean. Fever symptoms, various allergic symptoms,
Various complications and the like can be prevented, the cleaning operation can be performed safely, and there is no adverse effect on the line constituting materials due to the cleaning.

According to the method for removing endotoxin from a dialysate according to the second aspect of the present invention, the specific washing solution having the above-mentioned iron-removing action is used to produce a dialysate dilution water in artificial hemodialysis from within a reverse osmosis membrane device. Since at least a part of the water supply line leading to the dialysate preparation device is washed, the rust-like iron that has adhered and accumulated on the inner surface of each device constituting the line is removed, and is included in the adhesion accumulation layer. Endotoxins and other small substances that had been removed were also removed, and endotoxins that could not be removed by conventional disinfection washing or acid washing can be efficiently removed, and the reverse osmosis membrane filtered water used as dilution water for the dialysate is cleaned. As a result, the endotoxin in the dialysate produced using this dilution water can be reduced, and the endotoxin during the dialysis is transferred to the blood side in the same manner as described above. Symptoms, various allergic symptoms, it is possible to suppress the occurrence of various complications, also no adverse effects on the line the material by washing with safe to scrubbing.

According to the third aspect of the present invention, in the above-described method for removing endotoxin, there is an advantage that the detergent used is particularly excellent in the iron removing action and the endotoxin removing action.

According to the fourth aspect of the present invention, in the above endotoxin removal method, the cleaning liquid used is one in which the pH after one hour of residence in the line to be cleaned is set to a specific range, so that the cleaning liquid is used in conjunction with iron removal. There is an advantage that the action of removing endotoxin is sufficiently ensured, the generation of sulfurous acid gas due to the decomposition of the water-soluble reducing agent component in the cleaning solution is extremely reduced, and the safety of operation can be ensured.

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C077 AA05 BB01 BB02 EE03 HH02 JJ02 NN14 4D006 GA03 GA07 GA13 KC01 KC16 KD02 KD14 KD26 KD30 PA01 PB54 PC44

Claims (4)

[Claims] 1. a) 0.1 to 4 parts by weight of a water-soluble reducing agent containing dithionite as a main component per 100 parts by weight of water;
b) hydroxycarboxylic acid compound, carboxylic acid compound,
At least one type of P selected from aminocarboxylic acid compounds, phosphoric acid compounds, organic phosphonic acid compounds, and carbonate compounds;
At least a part of the dialysate supply line from the dialysate preparation device to the dialyzer in the artificial hemodialysis by the washing solution in which 0.05 to 6 parts by weight of the H buffer is dissolved and the initial PH is 6.0 to 8.0. A method for removing endotoxin from a dialysis solution, comprising washing dialysis fluid. 2. A washing liquid according to claim 1, wherein at least a part of a water supply line from a reverse osmosis membrane device for producing a dialysate dilution water in artificial hemodialysis to a dialysate preparation device is washed. A method for removing endotoxin from a dialysate. 3. The washing solution according to claim 1, wherein the water-soluble reducing agent is 60 to 100% by weight of a dithionate, a sulfite, a bisulfite, a pyrosulfite, a Rongalite, a thiourea dioxide, a thioglycolic acid, and a salt thereof. 3. The method for removing endotoxin in a dialysis solution according to claim 1, comprising 0 to 40% by weight of a reducing agent component selected from ascorbic acid and a salt thereof, and erythrobic acid and a salt thereof. 4. The cleaning liquid having an initial pH of 6.0 to 7.5,
In addition, the pH after one hour of residence in the line to be cleaned is 6.0 to 6.0.
4. It is set so as to be in the range of 7.0.
The method for removing endotoxin from a dialysate according to any one of the above.