JP2006250697A - Hydrogen peroxide gas sterilizing treatment system and detector of concentration of hydrogen peroxide gas in the system and detection method using detector - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a detection method of the concentration of a hydrogen peroxide gas constituted so as to enable automatic measurement, a detector therefor and a hydrogen peroxide gas sterilizing treatment system which uses the detection method and the detector to enable the control operation suitable for the sterilization due to the hydrogen peroxide gas in an solator. <P>SOLUTION: The hydrogen peroxide gas sterilizing treatment system is equipped with the isolator 1 having gas sampling regions 2 at a plurality of places, a gas-liquid mixing tank 5 for receiving a sampling gas to mix and react the same with the potassium permanganese solution introduced by a chemical injection pump 7, a gas flowmeter 4 for measuring the flow rate of the hydrogen peroxide gas, a degassing tank 8 for defoaming the reaction solution in the gas-liquid mixing tank 5, an absorptiometer 9 for allowing the defoamed reaction solution to flow to measure absorbance and an operator 10 for operating the concentration of the hydrogen peroxide gas on the basis of the absorbance measuring result and the correlation of preliminarily calculated absorbance with the concentration of the hydrogen peroxide gas and constituted so as to detect the concentration of the hydrogen peroxide gas in a real time by measuring the absorbance of the reaction solution. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  According to the present invention, hydrogen peroxide gas is supplied to a sterilization processing space (isolator) to maintain the hydrogen peroxide gas concentration within a predetermined range, and hydrogen peroxide is used to gas sterilize an object to be processed inside the isolator. The present invention relates to a gas sterilization system, and a hydrogen peroxide gas concentration detection apparatus and detection method in the system. In particular, the present invention can be suitably used for a sterilization apparatus system for sterilizing an object to be processed in an isolator constituting a processing assembly line for manufacturing a pharmaceutical container, a packaged pharmaceutical product, a medical device or the like in a pharmaceutical factory.

  It is well known that hydrogen peroxide gas is used as a disinfectant or a sterilizing agent in order to sterilize an object to be processed in an environmentally separated space, that is, an isolator.

  Since the hydrogen peroxide gas concentration in the isolator is decomposed and consumed in the isolator, an appropriate amount of hydrogen peroxide gas is always injected into the isolator for proper sterilization. It is necessary to keep the concentration range. A decrease in gas volume causes poor sterilization, while an excessive gas volume causes a large amount of hydrogen peroxide to be adsorbed on the wall of the device in the isolator, resulting in an exhaust time of the hydrogen peroxide gas from the isolator after the sterilization process. It becomes a cause of delinquency.

  For this reason, from the viewpoint of parametric resources, the biological indicator used by the user in basic experiments, etc. is determined in advance by setting the required hydrogen peroxide gas concentration and sterilization reaction time against the target value for sterilization guarantee. The required gas concentration is calculated using the above and the sterilization apparatus is operated so that the hydrogen peroxide gas concentration in the isolator is held at the calculated gas concentration for a predetermined time.

  By operating the sterilization apparatus as described above, it becomes possible to use the minimum hydrogen peroxide gas necessary for sterilization for the operation of the isolator, without causing poor sterilization and excessive suction. Without extending the exhaust time, it is possible to suppress the occurrence of corrosion of the entire apparatus due to long-term use. In addition, according to the current calculation of the expected hydrogen peroxide gas injection amount, the operation method in which sterilization validation was performed in conjunction with the use of a biological indicator is used for operation management such as measurement of the hydrogen peroxide gas concentration in the isolator. Monitoring makes it possible to cope with parametric resources that guarantee the sterilization effect in the isolator in real time without waiting for the culture result of the biological indicator. For that purpose, it is necessary to accurately measure the hydrogen peroxide gas concentration in the isolator in real time.

  By the way, as a method of measuring the concentration of hydrogen peroxide gas in the isolator, there is a manual analytical measurement method that is obtained by dissolving a certain amount of gas in water and chemically analyzing the water, and from the change in the infrared absorption spectrum. There are an instrumental analytical measurement method for obtaining the concentration, a sensor measurement method for performing measurement using a semiconductor sensor and other measurement sensors.

  As the above-mentioned manual analytical measurement method, for example, a potassium permanganate solution that oxidizes hydrogen peroxide is added to an aqueous solution containing hydrogen peroxide, and the oxidation-reduction potential due to the oxidation-reduction reaction is measured. Methods for measuring the concentration of hydrogen are known (see Patent Documents 1 to 5), but these measurement methods are excellent in measurement accuracy, but require analytical instruments, reagents, human hands, etc. Automation is difficult and real-time detection is not possible.

  In addition, the above-described instrumental analytical measurement method has a problem that the required detection cell length is large and the measurement apparatus is large, and the measurement accuracy with respect to sterilization validation is not so good and the cost is further increased.

  Furthermore, as a method for measuring the hydrogen peroxide gas concentration in the isolator in real time, methods and apparatuses disclosed in Patent Documents 6 to 8 are known.

  Patent Document 6 states that “the hydrogen peroxide gas concentration in the processing container (isolator) is always detected by a semiconductor gas sensor, and the hydrogen peroxide gas concentration in the processing container is set in advance according to the output of the semiconductor gas sensor. Disclosed is a gas sterilization method in which the supply amount of hydrogen peroxide gas is controlled in order to maintain the range. "

  However, when the semiconductor gas sensor described in Patent Document 6 is used, there are the following problems, and Patent Document 7 discloses a method and an apparatus for solving this problem. Regarding the above problems and the method and apparatus described in Patent Document 7, the description of Patent Document 7 will be cited below. First, let's talk about problems.

That is, even when the hydrogen peroxide vapor concentration in the processing container is kept constant, if the temperature or humidity in the processing container changes, the sensor output of the semiconductor gas sensor varies depending on the temperature or humidity. In other words, the conversion rate for converting the sensor output into the hydrogen peroxide vapor concentration is based on the data obtained under the condition that the temperature and humidity in the experimental container are kept constant, so the temperature or humidity varies. In actual sterilization, sterilization processing, and the like, there is a problem that the hydrogen peroxide vapor concentration converted from the sensor output by the conversion rate is different from the actual hydrogen peroxide vapor concentration in the processing container.
Therefore, Patent Document 7 states that “the problem of the conventional method is solved and the hydrogen peroxide vapor concentration (hereinafter referred to as“ container concentration ”) in the processing container is always maintained even under conditions in which the temperature or humidity in the processing container fluctuates. )) Can be accurately detected in real time, and a hydrogen peroxide vapor concentration detection method capable of efficiently and effectively performing treatment with hydrogen peroxide vapor such as sterilization and sterilization is provided. For the purpose of “providing a concentration detection apparatus that can be implemented in the present invention”, the following solution means is disclosed. FIG. 2 is a schematic view of the sterilization processing system disclosed in FIG. 1 in Patent Document 7, with a part number being changed.

  That is, the solution according to the invention of Patent Document 7 shown in FIG. 2 is “In the processing system in which the object to be processed 1 b is brought into contact with the hydrogen peroxide vapor 3 b in the processing container 2 b in which the pressure is kept constant, The concentration of hydrogen peroxide vapor in the container 2b is detected by the semiconductor gas sensor 71. The output of the semiconductor gas sensor 71 using the calculator 74c and the output of the semiconductor gas sensor using the temperature and humidity determined in advance as parameters. Based on the correlation data, the correction calculation is performed in relation to the humidity and temperature in the processing container 2 detected by the detectors 72 and 73, and the calculated value is displayed on the concentration display 75 as the hydrogen peroxide vapor concentration. It is made to be displayed ".

  In FIG. 2, 3a is exhaust gas, 4b is a hydrogen peroxide vapor generator, 5b is a supply line, 6b is an exhaust line, 8a is a hydrogen peroxide aqueous solution supply source, 8b is a hydrogen peroxide aqueous solution, and 9b is carrier air. Show.

  Incidentally, even when the semiconductor gas sensor as shown in FIG. 2 is used, there are the following problems. Since the amount of water vapor contained in the hydrogen peroxide gas in the processing container 2 fluctuates, it is necessary to measure the hydrogen peroxide gas concentration in real time even if correction based on the humidity measurement result is performed as described above. In some cases, there is a problem with accuracy. Furthermore, if the space of the processing container (isolator) is wide and the spatial distribution of the amount of water vapor contained in the hydrogen peroxide gas and the uniformity of temperature are not good, the measurement results differ depending on the position of the gas sampling port. However, the control accuracy of the hydrogen peroxide gas concentration in the isolator becomes a problem.

  Next, Patent Document 8 will be described. Patent Document 8 states that “a gas concentration detection method using an ionic conductor is used as a means for detecting a sterilization gas concentration in a sterilizer, and that accurate sterilization gas concentration detection can be obtained stably and in real time. In order to provide a sterilization gas concentration control device for a sterilization apparatus that can reliably and quickly control the sterilization gas concentration in the sterilization chamber to a desired condition by disclosing the following solution means.

  That is, “a gas concentration sensor using an ionic conductor and an appropriate humidity sensor are installed in the sterilization chamber, and the sterilization gas is subtracted from the detection value of the gas concentration sensor according to the detection value of the humidity sensor. The concentration is determined, and the supply of the sterilization gas to the sterilization chamber is controlled based on the concentration of the sterilization gas, and each electrode constituting the gas concentration sensor is formed in a comb shape, Disclosed is a sterilization gas concentration control device in a sterilization device, characterized in that it is disposed so as to be juxtaposed with each other.

In the case of the device of Patent Document 8 as well, as in the case of the device of Patent Document 7, there are problems in measurement accuracy and control accuracy based on humidity fluctuations and non-uniform humidity distribution.
JP-A-3-216543 JP-A-3-216544 JP-A-4-157356 JP-A-4-157357 Japanese Unexamined Patent Publication No. 4-320954 JP-A-9-131390 JP-A-11-160265 JP 2000-97906 A

  The present invention has been made in view of the above points, and an object of the present invention is to have a high measurement accuracy like the manual analytical measurement method and to simultaneously automate the instrumental analytical measurement method. It is an object of the present invention to provide a method and an apparatus for detecting the concentration of hydrogen peroxide gas in an isolator. Furthermore, the application of the above detection method and apparatus provides a hydrogen peroxide gas sterilization treatment system that can cope with parametric resources in sterilization validation and can perform suitable operation control of hydrogen peroxide gas sterilization in an isolator. is there.

  In order to solve the above-described problems, the present invention supplies hydrogen peroxide gas to a sterilization processing space (isolator) in order to keep the hydrogen peroxide gas concentration within a predetermined range, and the object to be processed inside the isolator In a hydrogen peroxide gas concentration detection method in a hydrogen peroxide gas sterilization processing system for gas sterilizing an object, the hydrogen peroxide gas in the isolator is sucked at a predetermined flow rate from at least one gas sampling port of the isolator. Then, the suction gas and a potassium permanganate solution having a predetermined flow rate set in advance are introduced and mixed in the gas-liquid mixing tank to react, and the reaction solution is passed through the degassing tank to degas it. The absorbance is measured by passing through an absorptiometer. Based on the result of the absorbance measurement and the correlation between the absorbance and the hydrogen peroxide gas concentration obtained in advance, Characterized by measuring the hydrogen peroxide gas concentration continuously (the invention of claim 1).

  According to the above detection method, hydrogen peroxide gas is diffused into a potassium permanganate solution and the absorbance of the reaction solution is measured, whereby the hydrogen peroxide gas concentration can be detected with high accuracy in real time.

  As an embodiment of the invention of claim 1, the invention of claim 2 is preferable. That is, in the detection method according to claim 1, the isolator has a plurality of gas sampling ports, and a switching valve for switching the gas sampling port is provided between the isolator and the gas-liquid mixing tank. The hydrogen peroxide gas concentration is measured by switching the detection position of the hydrogen oxide gas concentration (invention of claim 2). As a result, the measurement result does not differ unless the hydrogen peroxide gas concentration varies depending on the position of the gas sampling port, and thus the above-described problem of control accuracy of the hydrogen peroxide gas concentration in the isolator is solved. The distribution of the hydrogen peroxide gas concentration in the space in the isolator can be made uniform by flowing the gas in the space with, for example, a fan.

  Next, the invention according to claim 3 is preferable as the invention of the detection device. That is, an apparatus for carrying out the method for detecting a hydrogen peroxide gas concentration according to claim 1, wherein an isolator having at least one gas sampling port and a hydrogen peroxide gas sampling gas are introduced. , A gas-liquid mixing tank in which the potassium permanganate solution introduced by the chemical injection pump and the sampling gas are mixed and reacted, and hydrogen peroxide provided on a connection pipe between the gas sampling port and the gas-liquid mixing tank A gas flow meter for gas flow measurement, a degassing tank for degassing the reaction solution in the gas-liquid mixing tank, an absorptiometer for measuring the absorbance by flowing the degassed reaction solution, an absorbance measurement result and And a calculator for calculating the hydrogen peroxide gas concentration in the isolator based on the correlation between the obtained absorbance and the hydrogen peroxide gas concentration. ).

  Further, as the invention of the hydrogen peroxide gas sterilization system, the invention of claim 4 below is preferable. A hydrogen peroxide gas generator for supplying hydrogen peroxide gas to an isolator; a hydrogen peroxide gas concentration detection device according to claim 3; and a hydrogen peroxide gas based on an output signal from the detection device. And a control device that adjusts the amount of generation of the above (invention of claim 4).

  According to the present invention, it is possible to provide a hydrogen peroxide gas concentration detection method and detection device that have high measurement accuracy and that can simultaneously perform real-time automatic measurement, and that the detection method and device are applied. Thus, it is possible to provide a hydrogen peroxide gas sterilization processing system that enables suitable operation control of hydrogen peroxide gas sterilization in the isolator.

  An example of an embodiment of the present invention will be described below based on the drawings.

  FIG. 1 is a schematic configuration diagram of a hydrogen peroxide gas sterilization processing system showing an embodiment of the present invention. The hydrogen peroxide gas concentration detection apparatus shown in FIG. 1 introduces an isolator 1 having a plurality of gas sampling sites (gas sampling ports) 2 and a hydrogen peroxide gas sampling gas, and is introduced by a chemical injection pump 7. For measuring the hydrogen peroxide gas flow rate provided on the gas-liquid mixing tank 5 for mixing and reacting the potassium permanganate solution and the sampling gas, and the connecting pipe between the gas sampling port 2 and the gas-liquid mixing tank 5 Gas flow meter 4, degassing tank 8 for degassing the reaction solution in the gas-liquid mixing tank 5, an absorptiometer 9 for measuring the absorbance by flowing the defoamed reaction solution, and the absorbance measurement result are obtained in advance. And a calculator 10 for calculating the hydrogen peroxide gas concentration in the isolator based on the correlation between the absorbance and the hydrogen peroxide gas concentration.

  In FIG. 1, 3 is a switching valve, 6 is a potassium permanganate storage bottle, 11 is a waste liquid bottle, 12 is a control device that adjusts the amount of hydrogen peroxide gas generated based on an output signal from the calculator 10, 13 is a hydrogen peroxide gas generator for supplying hydrogen peroxide gas to the isolator 1, and 14 is a gas flow fan provided in the isolator 1.

  Next, details and operations of the configuration of FIG. 1 will be described. Gas sampling parts 2 provided at a plurality of locations of the isolator 1 and a gas flow meter 4 are connected via a switching valve 3. By switching the switching valve 3, the gas at an arbitrary location in the isolator 1 can be sucked. The switching valve 3 is connected to a gas flow meter 4 so that a certain amount of gas is always sucked. The suction gas is diffused in a potassium permanganate solution fed at a constant flow rate by a chemical pump 7 from a potassium permanganate storage bottle 6 in a gas-liquid mixing tank 5 connected to a gas flow meter 4. Well mixed with and reacts well.

  The reaction solution after the reaction is sent to the deaeration tank 8, and bubbles in the reaction solution are separated. The deaeration tank 8 is connected to an absorbance meter 9, and the absorbance of the reaction solution is measured by the absorbance meter 9. The measured absorbance value, suction gas flow rate value, potassium permanganate flow rate value, etc. at an arbitrary time are input to the calculator 10, and the absorbance measurement value and the correlation between the previously determined absorbance and the hydrogen peroxide gas concentration are used. Based on this, the sucked hydrogen peroxide gas concentration is calculated. The reaction solution discharged from the absorbance meter 9 is stored in the waste liquid bottle 11.

  The hydrogen peroxide gas concentration value calculated by the calculator 10 is transferred to the control device 12. The control device 12 computes a signal for adjusting the gas generation amount of the hydrogen peroxide gas generator 13 so that the obtained hydrogen peroxide gas concentration value is maintained at a set value set by the user for a certain period of time. The result is transmitted to the hydrogen peroxide gas generator 13. The hydrogen peroxide gas generator 13 sprays hydrogen peroxide gas into the isolator 1 according to the obtained signal value. If the distribution state of the hydrogen peroxide gas in the isolator 1 is not uniform, the fan 14 provided in the isolator 1 is rotated to make the hydrogen peroxide gas concentration distribution in the isolator 1 uniform.

The schematic block diagram of the hydrogen peroxide gas sterilization processing system which shows embodiment of this invention. Schematic of the conventional sterilization processing system disclosed in Patent Document 7.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Isolator 2 Gas sampling part 3 Switching valve 4 Gas flow meter 5 Gas-liquid mixing tank 6 Potassium permanganate preservation bottle 7 Chemical injection pump 8 Deaeration tank 9 Absorbance meter 10 Calculator 11 Waste liquid bottle 12 Controller 13 Hydrogen peroxide gas Generator 14 Fan

Claims (4)

Hydrogen peroxide gas sterilization system that supplies hydrogen peroxide gas to the sterilization space (isolator) and gas sterilizes the object to be processed inside the isolator in order to maintain the hydrogen peroxide gas concentration within a predetermined range. In the method for detecting the concentration of hydrogen peroxide gas, the hydrogen peroxide gas in the isolator is sucked at a predetermined flow rate from at least one gas sampling port of the isolator, and the suction gas and a predetermined flow rate The potassium permanganate solution was introduced and mixed in the gas-liquid mixing tank, reacted, and the reaction solution was passed through the degassing tank to degas, then passed through an absorptiometer to measure the absorbance, Based on this absorbance measurement result and the correlation between the previously obtained absorbance and the hydrogen peroxide gas concentration, the hydrogen peroxide gas concentration in the isolator is continuously measured. Detection method for hydrogen peroxide gas concentration in the hydrogen peroxide gas sterilization system according to claim. 2. The detection method according to claim 1, wherein the isolator has a plurality of gas sampling ports, and includes a switching valve that switches a gas sampling port between the isolator and a gas-liquid mixing tank, and hydrogen peroxide gas A method for detecting a hydrogen peroxide gas concentration in a hydrogen peroxide gas sterilization system, wherein the concentration detection position is switched to measure the hydrogen peroxide gas concentration. An apparatus for carrying out the method for detecting a hydrogen peroxide gas concentration according to claim 1 or 2, wherein an isolator having at least one gas sampling port and a hydrogen peroxide gas sampling gas are introduced, A gas-liquid mixing tank in which the potassium permanganate solution introduced by the pump and the sampling gas are mixed and reacted, and a hydrogen peroxide gas flow rate provided on a connection pipe between the gas sampling port and the gas-liquid mixing tank A gas flow meter for measurement, a deaeration tank for degassing the reaction solution in the gas-liquid mixing tank, an absorptiometer for measuring the absorbance through the degassed reaction solution, and an absorbance measurement result were obtained in advance. A hydrogen peroxide gas sterilization process, comprising a calculator for calculating the hydrogen peroxide gas concentration in the isolator based on the correlation between the absorbance and the hydrogen peroxide gas concentration; Detector of the hydrogen peroxide gas concentration in the system. A hydrogen peroxide gas generator for supplying hydrogen peroxide gas to an isolator; a hydrogen peroxide gas concentration detection device according to claim 3; and generation of hydrogen peroxide gas based on an output signal from the detection device A hydrogen peroxide gas sterilization system comprising a control device for adjusting the amount.

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