JP4633430B2 - Chemical liquid preparation device and chemical liquid preparation method - Google Patents

Description

  The present invention relates to a chemical liquid preparation apparatus and a chemical liquid preparation method for obtaining a sterile chemical liquid in which target components are adjusted to a predetermined concentration from a plurality of raw materials.

  Conventionally, a suitable means for obtaining a sterile chemical solution in which a target component is adjusted to a predetermined concentration has been demanded. For example, an injection used for medical treatment corresponds to such a chemical solution, and a better means for obtaining it is required. The injection is prepared by, for example, mixing a liquid compound or powdered solid substance as a medicinal component with purified water for injection for dissolution, and dissolving the medicinal component in the liquid compound or solid at a predetermined concentration. Manufactured as a sterile chemical solution.

  Of course, since injections are subject to strict conditions regarding the concentration and sterility of medicinal ingredients, the compounding device, which is the means used to manufacture injections, also achieves high concentration accuracy and is sterile. It must be able to maintain state. In addition, there seems to be no prior literature regarding means for obtaining an aseptic drug solution whose target component is adjusted to a predetermined concentration.

  However, for example, when a float switch and a float type liquid level gauge are used to measure the amount of liquid that has entered the tank constituting the preparation device, the amount of liquid cannot be measured accurately, and the liquid compound or water for injection to be mixed cannot be measured. The amount may fluctuate. Moreover, since the piping which comprises a float type liquid level gauge is thin and is inferior to sterilization and washing | cleaning property, it is difficult to suppress generation | occurrence | production of a living microbe. For this reason, there is a problem that it is difficult to produce a high-quality injection with a high sterility while maintaining a high yield even when using a sterile liquid compound and water for injection.

  The present invention has been made in view of the above-described problems, and provides a suitable means for obtaining a high-quality chemical solution in which a target component is adjusted to a predetermined concentration with high yield and high recovery rate and is sterile. Let it be an issue. As a result of repeated studies to solve the problem, it has been found that the problem can be solved by the following means, and the present invention has been completed.

  First, according to the present invention, a chemical preparation apparatus that mixes a plurality of raw materials, and after a target component is adjusted to a predetermined concentration, is sterilized by filtration to obtain a chemical that needs to be aseptic. A preparation tank for receiving a plurality of raw materials and mixing them at a predetermined ratio to obtain a preparation liquid; a filter connected to the preparation tank through a communication main channel; And a filtrate tank that is connected to the vessel through a communication main flow path and receives the sterile-filtered preparation liquid. The preparation tank further comprises a liquid volume measuring means for measuring the liquid volume of the raw material or the preparation liquid. A chemical preparation device in which the amount measuring means is a load cell or a pressure gauge is provided.

  The raw material refers to (individual) liquid or solid (powder) before being mixed, and sterile, pyrogen-free water obtained by subjecting purified water to further membrane filtration or distillation is also included in the raw material. included. The chemical solution in which the target component is adjusted to a predetermined concentration means a preparation solution in which the target component has a predetermined concentration as ordered. By sterility is meant sterilized and in a sterile state. The filter refers to a device having a filtering function, and its specific specification is not limited. As a preferred filter, a plastic (polymer resin) filter element sterilized in advance is housed in a stainless steel container. The filtration accuracy of the filter is not limited, but is preferably in the range of 0.1 to 0.5 μm, and more preferably 0.2 μm. Moreover, although not limited, it is preferable to provide the filter in multiple stages in series because the sterilization of the chemical solution can be achieved more reliably. In this specification, filtration by a filter is also expressed as sterile filtration.

  Means for receiving a plurality of raw materials in a preparation tank and means for transferring a preparation liquid (chemical liquid whose target component is adjusted to a predetermined concentration) mixed and mixed at a predetermined ratio to the next step are not limited. For example, each raw material is supplied from a separately provided manufacturing means to a preparation tank, and each raw material is received through an introduction main flow path, and the chemical obtained through the delivery main flow path is transferred from the filtrate tank to a separate chemical filling means. Etc. It refers to a channel and a channel that is not open. A preferable channel is a pipe made of stainless steel (SUS316L) finished with buff # 200 to 800 and further subjected to electrolytic polishing.

  The chemical liquid preparation device according to the present invention further comprises a gas supply means for supplying sterile gas to the preparation tank, and supplies the liquid by pressing the liquid level of the preparation liquid in the preparation tank by supplying sterile gas. It is preferable to perform aseptic filtration and transfer of the preparation liquid from the tank to the filtrate tank through the filter.

  That is, it is preferable not to use a pump as the transfer means. Since the gas supply means is means for supplying aseptic gas to the preparation tank, it is preferable to include means for maintaining the sterility of the gas or sterilizing the gas. For example, it is desirable to provide means for sterilizing and supplying sterilized equipment (bent filter) and receiving supply of pressurized gas.

  In addition, the chemical preparation apparatus according to the present invention further includes gas supply means for supplying sterile gas to the communication main flow path connecting the preparation tank and the filter, and the preparation tank and the filter are supplied by supplying sterile gas. It is preferable to press the preparation liquid remaining in the communication main flow path connecting the filter, the filter, and the communication main flow path connecting the filter and the filtrate tank, and to send the solution to the filtrate tank.

  The chemical liquid preparation device according to the present invention has a complete discharge structure in which the preparation tank has a discharge port in the deepest part, and the preparation tank, the filter, and the filtrate tank are installed so as to be lower in that order, and at least It is preferable that the connecting main flow path connecting the preparation tank and the filter, and the filter and the filtrate tank are each formed with a gradient of 1/100 or more. As a preparation tank provided with a complete discharge structure, for example, a tank having a cone shape at the bottom is exemplified.

  It is preferable to use a stainless steel pipe (SUS316L) formed with a gradient of 1/80 or more, finished with buff # 400, and further subjected to electrolytic polishing. The upper limit of the gradient is not particularly limited, but if the gradient is too large, the height required for the apparatus also increases. Therefore, considering this, the preferable gradient is approximately 1/75 to 1/100.

  The chemical preparation apparatus according to the present invention further includes a gas supply means for supplying an inert gas used for deoxygenation of the raw material or the preparation liquid to the preparation tank, and configures the gas supply means to enter the preparation tank. It is preferable that a bubbling nozzle is provided at the tip of the flow path.

  The mode of the bubbling nozzle is not limited, and may be a commercially available nozzle or simply a pipe with a small hole. However, since the chemical liquid preparation device according to the present invention obtains aseptic chemical liquid, it is sterilizable. It is preferable to have a structure with excellent detergency and no accumulation. In addition, it is preferable to have a structure that can be discharged so that the chemical solution does not enter the bubbling nozzle and accumulate. For example, preferable bubbling nozzles include those having a structure in which small holes are opened so that bubbles are emitted toward the bottom of the preparation tank, and those having a structure in which small holes are formed on the entire surface of the nozzle. The bubbling nozzle is preferably installed perpendicularly or parallel to the inner wall surface of the preparation tank.

  Preferable examples of the inert gas include nitrogen gas and argon gas. The gas supply means may not include an inert gas production apparatus. As a minimum configuration, the gas supply means includes a separately provided inert gas production apparatus or a flow path (pipe) and a valve connected to an inert gas storage tank. The minimum configuration can be obtained.

  The chemical liquid preparation apparatus according to the present invention further includes a dedicated sterilization steam channel or cleaning liquid supply channel for supplying sterilization vapor or cleaning liquid used for sterilization or cleaning inside the preparation tank to the preparation tank. It is preferable that a shower ball is provided at the tip of each of the dedicated sterilization vapor flow path or cleaning liquid supply flow path that enters the preparation tank.

  The form of the shower ball is not limited, but it is preferably a spherical one that can be sprayed in the direction of approximately 360 ° and having a structure without stagnation and excellent sterilization and cleaning properties. The number of shower balls is not limited, but it is preferable to provide two or more shower balls so as to eliminate portions that cannot be sprayed. For example, in the case where a stirrer is provided, if there is one shower ball, it may not be possible to spray the back of the shaft of the stirrer, but if there are two or more, the problem can be solved. For example, when the preparation tank is viewed from above, an arbitrary reference position is 0 °, and one shower ball is provided between 45 ° and 135 °, and the other is 225 ° to 315. It is preferable to provide between.

  The chemical preparation apparatus according to the present invention further includes a stirrer for mixing in the preparation tank, and a sterilization steam dedicated for supplying sterilization steam or cleaning liquid used for sterilization or cleaning of the shaft of the stirrer to the preparation tank. It is preferable to have a flow path or a cleaning liquid supply flow path.

  As the sterilization steam used for sterilization of the inside of the preparation tank and the shaft of the stirrer, it is preferable to use pure steam containing no pyrogen produced from purified water, and the temperature is not limited. It is desirable that the temperature is 100 to 140 ° C. at the end (where sterilization is performed), and the temperature holding time is desirably 10 minutes to 60 minutes. The cleaning liquid used for the cleaning is not limited, and an alkaline liquid containing caustic soda, an acidic liquid containing nitric acid, citric acid and oxalic acid, or various anionic, cationic and nonionic surfactants can be employed.

  The chemical preparation apparatus according to the present invention further includes a valve for branching the communication main channel in the communication main channel connecting the preparation tank and the filter, and the filter and the filtrate tank, and at least the valve is sanitary. The diaphragm valve is preferably a three-way valve.

  It is more preferable that not only the valve for branching the communication main flow path but also all the valves for branching the flow path provided in the apparatus are three-way valves.

  The chemical liquid preparation device according to the present invention further includes a plurality of drainage channels branched from the main tank connecting the preparation tank and the filter, and the filter and the filtrate tank, and the plurality of drainage channels are provided. It is preferable that the filter is cut at the primary side and the secondary side.

  Here, the edge cutting refers to a state in which means that are not in direct communication and at least can be shut off are provided. The primary side of the filter refers to the upstream side (the supply side of the liquid to be filtered) of the medium (for example, the filter) that performs the filtering function in the filter regardless of the inside or outside of the filter, and the secondary side similarly It refers to the downstream side (the production side of the filtered liquid (filtrate)).

  The chemical preparation device according to the present invention further includes an air vent channel connected to the primary side of the filter itself, and further includes a detector that detects the presence or absence of air in the air vent channel. Preferably there is.

  The primary side of the filter itself refers to the upstream side (the supply side of the liquid to be filtered) of the medium (for example, the filter) that performs the filtering function in the filter. The connection position of the air vent channel to the filter is preferably provided on the upper side of the communication main channel connected to the filter. The air vent channel is preferably provided with a valve at the top of the filter in order to completely vent the air of the filter itself. Moreover, although the specific aspect of a detector is not limited, For example, a tuning fork type level switch can be employ | adopted.

  It is preferable that the chemical | medical solution preparation apparatus which concerns on this invention provides a predetermined | prescribed adapter in the flow path connected to a filter, and can use the filter from which size differs.

  For example, when the flow path is a pipe, a short pipe that adjusts the length of the connected pipe can be adopted as the adapter. Filters having different sizes mean filters having different filtration areas (or membrane areas in the case of filters).

  Next, according to the present invention, a preparation tank that receives a plurality of raw materials and mixes them at a predetermined ratio to obtain a preparation liquid, and is connected to the preparation tank through a communication main flow path. A filter tank connected to the filter through a communication main flow path and receiving a sterile filtered preparation liquid, an introduction main flow path for introducing the raw material into the preparation tank, Gas supply means for supplying an inert gas used for deoxygenation to the preparation tank, a bubbling nozzle provided at the tip of the flow path constituting the gas supply means and entering the preparation tank, and sterilization inside the preparation tank Or a dedicated sterilization steam channel or cleaning liquid supply channel for supplying sterilization vapor or cleaning liquid used for cleaning to the preparation tank, and a dedicated sterilization steam channel or cleaning liquid supply flow that enters the preparation tank. Provided at each end of the road Hour ball, a stirrer for mixing in the preparation tank, a preparation tank and a filter, a communication main channel connecting the filter and the filtrate tank, a plurality of drainage channels branched from the communication main channel, and a filter A chemical liquid preparation method for obtaining an aseptic chemical liquid in which a target component is adjusted to a predetermined concentration from a plurality of raw materials, using a chemical liquid preparation apparatus further having an air vent channel connected to the primary side of the apparatus, At least the cleaning of the preparation tank, filter, filtrate tank, introduction main flow path, bubbling nozzle, shower ball, stirrer shaft, drainage flow path, and air vent flow path are divided into multiple stages for each batch. A method for preparing a chemical solution is provided.

  Here, one batch means a single treatment (one preparation step of a chemical solution) for obtaining a desired chemical solution in which the target component is adjusted to a predetermined concentration and is sterile. Multiple stages are two or more stages. For example, first, the main introduction channel, bubbling nozzle, and shower ball are washed at once, and then the agitator shaft, drainage channel, and air vent channel are washed at once. Then, the cleaning is divided into two stages.

  In the chemical preparation method according to the present invention, at least the preparation tank, the filtrate tank, the filter, the introduction main flow path, the bubbling nozzle, the shower ball, the shaft of the stirrer, the drainage flow path, and the air vent flow path. It is preferable to carry out the cleaning in a separate manner for each batch.

  Individually, the cleaning means the most divided stage among a plurality of stages, and in one cleaning, a preparation tank, a filtrate tank, a filter, an introduction main channel, a bubbling nozzle, a shower ball, a shaft of a stirrer, This is a cleaning in which only one of the drainage flow path and the air vent flow path is performed, and is a method of cleaning all.

  In the chemical liquid preparation method according to the present invention, at least the preparation tank, the filtrate tank, the filter, the introduction main flow path, the bubbling nozzle, the shower ball, the shaft of the stirrer, the drainage flow path, and the air vent It is preferable to sterilize the flow path in a plurality of stages for each predetermined batch.

  Each predetermined batch means a predetermined frequency of one batch or more, and may be every batch. The frequency can be determined, for example, by confirming sterility within the apparatus system using a biological indicator, a chemical indicator, or the like.

  In the chemical liquid preparation device according to the present invention, since the liquid amount measuring means provided in the preparation tank is a load cell or a pressure gauge, the liquid amount can be measured continuously and accurately. Therefore, it is possible to mix a plurality of raw materials with high accuracy according to a predetermined ratio. That is, it is easy to prepare a chemical solution with high accuracy. Further, since the load cell or pressure gauge can be installed outside the tank, it does not come into contact with the liquid and has good sterilization and cleaning properties. Therefore, it is possible to obtain a chemical solution (prepared solution) in which the target component is adjusted to a predetermined concentration while maintaining the sterile condition without contaminating the raw material with live bacteria. Therefore, it is possible to obtain a high-quality chemical solution that is sterile and has a target component adjusted to a predetermined concentration with a high yield.

  Furthermore, in the float type switch, fine particles may be generated due to friction between the float and the shaft, but in the load cell or the pressure gauge, this possibility can be eliminated. In addition, if you want to change the control point of the liquid level, it is necessary to adjust the (hardware) itself in the float type liquid level gauge, but in the load cell or pressure gauge, it is only necessary to process the electrical signal. Adjustment is easy.

  Since the chemical compounding device according to the present invention preferably does not use a pump as the transfer means, the component of the chemical solution prepared is decomposed due to the heat generated by the sliding action of the seal part of the pump, and the concentration of the target component fluctuates. The fear can be eliminated. Further, it is possible to eliminate the possibility that the composition of the component is destroyed by the shear stress of the impeller of the pump and the target component does not reach a predetermined concentration.

  The chemical liquid preparation apparatus according to the present invention preferably has a complete discharge structure in which the preparation tank has a discharge port at the deepest portion, so that accumulation or the like hardly occurs and can be transferred to the filtrate tank without waste. In addition, the preparation tank, the filter, and the filtrate tank are installed so as to be lower in that order, and at least the communication main flow path connecting the preparation tank and the filter and the filter and the filtrate tank is 1/100 or more. Since it is formed with a gradient, accumulation or the like hardly occurs here. Therefore, it is easy to maintain a sterilized state, and it is possible to avoid the problem that the concentration of the target component of the chemical solution prepared in the preparation tank is caused by unintended mixing of the residual solution. Moreover, the prepared chemical solution can be recovered at a high recovery rate, and further, the head loss (energy) required for the transfer can be reduced, and the device is an energy saving device. The liquid level of the prepared solution in the preparation tank is reduced. The supply pressure of the sterilized gas required for transferring the preparation liquid by pressing can be further reduced.

  The chemical liquid preparation apparatus according to the present invention preferably includes a gas supply means for supplying an inert gas used for deoxygenation of the stock solution or the preparation liquid to the preparation tank, and the flow path that is the gas supply means in the preparation tank is provided. Since the bubbling nozzle is provided at the tip, changes (oxidation and deterioration) of the prepared chemical can be prevented. Moreover, it is advantageous for suppressing the growth of aerobic bacteria in the preparation tank.

  The chemical liquid preparation apparatus according to the present invention preferably has a dedicated sterilization vapor channel or cleaning liquid supply channel for supplying sterilization vapor or cleaning liquid used for sterilization or cleaning inside the preparation tank to the preparation tank. Since the shower ball is provided at the tip of each of the dedicated sterilization vapor channel or cleaning liquid supply channel inside the preparation tank, the entire inside of the preparation tank can be easily sterilized or cleaned, and the aseptic state is maintained. Is easy.

  The chemical preparation apparatus according to the present invention preferably includes a stirrer for mixing in a preparation tank, and a sterilization steam dedicated for supplying sterilization steam or cleaning liquid used for sterilization or cleaning of the shaft of the stirrer to the preparation tank. Since the flow path or the cleaning liquid supply flow path is provided, the shaft can be reliably sterilized or cleaned, and the preparation tank is hardly contaminated from the outside of the seal portion between the preparation tank and the rotating shaft.

  The chemical liquid preparation device according to the present invention is preferably a three-way valve that branches the communication main flow path connecting the preparation tank and the filter, and the filter and the filtrate tank. The rate is increased, and the risk of generation of viable bacteria and fluctuations in the concentration of the target component in the chemical solution is reduced.

  The chemical liquid preparation device according to the present invention preferably has a plurality of drainage channels branched from a communication main channel connecting the preparation tank and the filter, and the filter and the filtrate tank. Since the primary side and the secondary side of the filter are cut off, the sterilization of the secondary side after the secondary side is sterilized is less likely to reverse the sterility and the sterilization state is reduced. Sterility can be maintained.

  The chemical liquid preparation device according to the present invention preferably has an air vent channel connected to the primary side of the filter itself, and includes a detector for detecting the presence or absence of air in the air vent channel. The air is surely extracted before filtration, and there is little possibility of causing an air lock when filtering and reducing the filtration efficiency.

  Since the chemical | medical solution preparation apparatus which concerns on this invention is provided with the predetermined | prescribed adapter in the flow path connected to a filter preferably, and can use the filter from which size differs (different filtration area), the liquid (target component is the target component) When the permeation rate (filtration rate) (viscosity, etc.) changes depending on the chemical solution adjusted to a predetermined concentration, it can be appropriately handled. For example, if the same filter is used to filter a liquid (chemical solution) having a lower permeation rate and a higher viscosity, it takes a lot of time unless the pressure is changed, and the processing efficiency of the apparatus decreases. According to the preferred embodiment, since it can be replaced with a filter having a larger size (wide filtration area), such a situation can be avoided. In general, in a filter, if the liquid to be filtered is the same and the pore diameter is the same, the larger the filtration area, the shorter the filtration time can be. A low liquid (chemical solution) can be filtered.

  The chemical liquid preparation method according to the present invention is preferably divided into a plurality of stages for each batch of cleaning of at least the introduction main flow path, the bubbling nozzle, the shower ball, the shaft of the stirrer, the drainage flow path, and the air vent flow path. Is performed separately for each batch, so that cleaning can be performed more reliably, and the stock solution or chemical solution (preparation solution) used in the previous treatment is prevented from remaining, preventing cross-contamination when preparing different products. It is suitable for obtaining a chemical solution having a target component at a predetermined concentration. In addition, the load on the incidental equipment for supplying the cleaning liquid and receiving the waste liquid after the cleaning can be suppressed, and it can be made smaller (small capacity, low cost).

  In the chemical liquid preparation method according to the present invention, preferably, at least the introduction main flow path, the bubbling nozzle, the shower ball, the shaft of the stirrer, the drainage flow path, and the air vent flow path are sterilized in a plurality of stages for each predetermined batch. Since it is performed separately, it can be sterilized more reliably and is suitable for obtaining an aseptic drug solution. In addition, the load on the incidental equipment (pure steam generator) for supplying the sterilization steam can be suppressed, and the size can be reduced (small capacity, low cost).

  Hereinafter, embodiments of the present invention will be described with reference to the drawings as appropriate. However, the present invention should not be construed as being limited to these, and those skilled in the art will be able to do so without departing from the scope of the present invention. Various changes, modifications and improvements can be made based on the knowledge. For example, the drawings show preferred embodiments of the present invention, but the present invention is not limited by the modes shown in the drawings or the information shown in the drawings. In practicing or verifying the present invention, means similar to or equivalent to those described in the present specification can be applied, but preferred means are those described below.

  In this specification, the terms “preparation” and “preparation” are generally used as synonyms in the sense that a target component is adjusted to a predetermined concentration (chemical solution). The former is used as the part. Further, the filter is an essential component of the chemical compounding device according to the present invention, and aseptic filtration constitutes a part of the preparation process of the chemical compounding method according to the present invention. This means is not intended to include the concept of filtration or aseptic filtration.

  First, an embodiment of a chemical liquid preparation device according to the present invention will be shown, and the role of components according to the embodiment will be described. FIG. 1 is a flowchart schematically showing one embodiment of a chemical liquid preparation device according to the present invention.

  1 mainly includes a preparation tank 2, a sterile filter 3 constituting a filter (equipment having a filtration function), and a filtrate tank 4, which are made of stainless steel (SUS316L). Connection main pipes (flow paths) 21 and 22 are connected. As shown in FIG. 1 which is a flow chart, the chemical liquid preparation device 1 is provided with the sterile filter 3 so as to be lower than the bottom of the preparation tank 2, and the filtrate tank 4 is set so that the upper part thereof is lower than the sterile filter 3. Although not clearly shown in FIG. 1, the communication main pipes 21 and 22 are arranged with a gradient of 1/80. Furthermore, the filtrate tank 4 also has a complete discharge structure with a discharge port at the deepest part, and the introduction main pipe 23 and the delivery main pipe 24 are also arranged with a 1/80 gradient.

  The medicinal solution preparation apparatus 1 uses water for injection (WFI) and a raw material containing a certain medicinal component as a plurality of stock solutions, and after mixing them, aseptically filtered, the target medicinal component Is a device capable of obtaining a sterile injection (corresponding to a drug solution) adjusted to a predetermined concentration.

  The preparation tank 2 is a stainless steel (SUS316L) tank for receiving water for injection and liquid compounds (corresponding to a plurality of stock solutions) and mixing at a predetermined ratio to obtain an injection. The preparation tank 2 has at least an inner surface subjected to electrolytic polishing to prevent elution of metal ions and the like, and further, a substance constituting dirt is not easily deposited, and is easy to clean. Furthermore, by adopting a complete discharge structure having a discharge port at the deepest part, it is possible to prevent the remaining of the injection and to facilitate adaptation to transfer without using a pump.

  In the chemical liquid preparation apparatus 1, water for injection is supplied from the respective manufacturing apparatuses (not shown) separately provided through the introduction main pipe (flow path) 23 provided with the valve 53 and the valve 52 and the liquid introduction pipe 32 at the tip thereof. To be introduced. The raw material is introduced into the preparation tank 2 manually or automatically depending on the amount. The preparation tank 2 is provided with a load cell 33 that can measure the amount of liquid without being in contact with the liquid to be measured (water for injection and liquid compound) outside, and water or liquid for injection introduced into the preparation tank 2. The liquid amount of the compound and the injection prepared by mixing them can be measured by load conversion.

  For example, by receiving a predetermined amount of water for injection first while measuring with the load cell 33, and then adding a predetermined amount of raw material while measuring with the load cell 33, or by adding a pre-weighed amount of raw material The water for injection and the liquid compound can be mixed at a predetermined ratio, and the medicinal component (target component) applied to the raw material in the injection can be adjusted to a predetermined concentration.

  The preparation tank 2 includes a stirrer, and the stirrer is introduced into the preparation tank by rotating the stirring blade supported by the shaft 31 with an electric motor (M in FIG. 1) provided outside the tank. Thoroughly mix the water for injection and the ingredients.

  In addition to water for injection and raw materials, the chemical liquid preparation device 1 includes steam used for sterilization of the entire device including the compressed air used for transferring the injection, the inside of the preparation tank 2, the stirrer, the aseptic filter 3, and the filtrate tank 4. (Pure steam, steam for sterilization), as well as caustic soda cleaning solution, nitric acid cleaning solution, surfactant (cleaning solution) used for cleaning the entire apparatus, nitrogen used for deoxygenation of injection (chemical solution) in the preparation tank 2 Gas (inert gas) is supplied.

  In the chemical compounding device 1, the compressed air sent from a compressor (device for pressurizing the gas) or the like (not shown) is sterile filtered through the pipe 61 by the vent filter 34 that constitutes the gas supply means together with the pipe 61. Is maintained or sterilized and supplied to the preparation tank 2 as sterile air. The liquid level of the injection in the preparation tank 2 is pressed by the supply of aseptic air, and the injection is not the pump, and the deepest part of the preparation tank 2 having a complete discharge structure having a discharge port at the deepest part. Are sent to the aseptic filter 3 through the communication main pipe 21 provided with the valves 51 and 54, filtered by the pressure caused by the supply of aseptic air, subjected to aseptic processing, and further transferred to the filtrate tank 4. In addition, the vent filter used in the chemical preparation apparatus 1 including the vent filter 34 is a stainless steel in which a filter element made of PTFE (polytetrafluoroethylene) and PP (polypropylene) is subjected to electrolytic polishing finish at least on the inner surface. It is housed in a housing (container) made of (SUS316L), and its filtration accuracy is, for example, 0.2 to 0.45 μm.

  In the chemical preparation apparatus 1, the completion of the transfer of the injection is detected by the load cell 33 of the preparation tank 2 that there is no injection in the preparation tank 2, but the pressure gauge 36 (see FIG. 1) is detected. PIA of the inside preparation tank 2, which is different from a pressure gauge that can be used as a substitute for a load cell), and its internal pressure is constantly monitored, and abnormal when it rises above a pre-defined pressure It is judged, a warning is issued, and the transfer of the injection solution by introducing sterile air into the preparation tank 2 is stopped. In addition to the valve 51 provided in the vicinity of the bottom of the preparation tank 2, the communication main pipes 21 and 22 are provided with a plurality of valves. For example, when these valves are not opened and cannot be transferred, this is an example that may be determined as abnormal. .

  In the chemical compounding apparatus 1, steam and cleaning liquid are sent from a not-shown pure steam generator, cleaning liquid storage tank, supply device, etc., and are introduced into the preparation tank 2 through a dedicated pipe 62 provided with a valve 72 branched through an introduction main pipe 23. Is done. The pipe 62 branches into two before entering the preparation tank 2, and is inserted into the preparation tank 2 so as to be in a symmetrical position with the shaft 31 in between. Each tip is provided with one shower ball 35 inside the preparation tank 2.

  The steam and the surfactant supplied by the pipe 62 and the shower ball 35 are mainly used for cleaning or sterilizing the inside of the preparation tank 2, while mainly for cleaning or sterilizing the shaft 31 of the stirrer. The steam and the cleaning liquid are introduced into the preparation tank 2 via the attachment part of the shaft 31 to the preparation tank 2 by a dedicated pipe 63 provided with a valve 73 branched through the introduction main pipe 23. The preparation tank 2 is equipped with a thermometer 37 (TISA of the preparation tank 2 in FIG. 1), the temperature of the steam is monitored, and when the temperature of the steam is out of the specified range, an alarm is issued and a sterilization operation is performed. Is canceled.

  In the chemical compounding apparatus 1, the nitrogen gas is supplied from a nitrogen production apparatus (not shown) and branched through the introduction main pipe 23, and the nitrogen gas is prepared by a dedicated pipe 64 provided with a valve 74 constituting gas supply means. 2 is introduced. A bubbling nozzle 38 is provided at the tip of the pipe 64 inside the preparation tank 2. When fine bubbles of nitrogen gas are blown into the injection prepared in the preparation tank 2 through the bubbling nozzle 38, oxygen contained in the injection moves into the air and the injection is deoxygenated.

  In the chemical preparation apparatus 1, the aseptic filter 3 is a stainless steel (SUS316L) housing in which at least an inner surface of a filter element made of hydrophilic PVDF (polyvinylidene fluoride) and PP (polypropylene) is subjected to electrolytic polishing finish. The filtration accuracy is 0.22 μm, for example.

  In addition, although the chemical | medical solution preparation apparatus 1 has one aseptic filter, in the chemical | medical solution preparation apparatus which concerns on this invention, as FIG. 7 shows, an aseptic filter can be comprised in 2 steps | paragraphs in series. In this case, it is desirable that the front-stage aseptic filter and the subsequent-stage aseptic filter have the same filtration accuracy. This is because the duplexing improves safety.

  The chemical compounding apparatus 1 includes an air vent pipe 86 that is connected to the primary side of the aseptic filter 3 itself and away from the communication main pipe 21 connected to the aseptic filter 3. The air vent pipe 86 is provided with a tuning fork type level switch 39 (LS in FIG. 1) as a detector for detecting the presence or absence of air. Further, a pressure gauge 40 (PIA near the sterile filter 3 in FIG. 1) is provided near the inlet of the sterile filter 3 of the communication main pipe 21 to detect a pressure increase (abnormality) due to clogging of the sterile filter 3.

  Although not clearly shown in the chemical liquid preparation device 1 shown in FIG. 1, in the chemical liquid preparation device according to the present invention, a short pipe is provided as an adapter in a pipe (flow path) connected to a sterile filter (filter). Thus, aseptic filters of different sizes can be used. An example is shown in FIGS. 8A and 8B. For example, as shown in FIG. 8 (a), when the aseptic filter 181 is installed, if a short pipe 183 connected to the air vent pipe 184 is provided, the direction of connection to the air vent pipe 184 (see FIG. 8). It is possible to replace the aseptic filter 182 longer than the aseptic filter 181 in the upward direction.

  In the liquid medicine preparation apparatus 1, the injection prepared by the preparation tank 2 and subjected to aseptic filtration with the sterile filter 3 passes through the communication main pipe 22 provided with the valves 55 to 57 and the liquid introduction pipe 42 at the tip thereof to the filtrate tank. Accepted to 4.

  The filtrate tank 4 is a stainless steel (SUS316L) tank that is connected to the sterile filter 3 through the communication main pipe 22 and receives a sterile injection that is sterile filtered by the sterile filter 3. Like the preparation tank 2, the filtrate tank 4 is subjected to electrolytic polishing finish at least on the inner surface to prevent elution of metal ions and the like, and the deposition of substances constituting dirt and the like is prevented, and the washing tank is clean. Improvement is achieved. Furthermore, by adopting a complete discharge structure having a discharge port at the deepest part, it is possible to prevent the remaining of the injection and to facilitate adaptation to transfer without using a pump.

  In the chemical liquid preparation device 1, the injection is stored in this filtrate tank before being sent to the next process (for example, a filling machine), and aseptic air is used to transfer the injection from the filtrate tank 4 to the next process. Is done. In the chemical liquid preparation apparatus 1, compressed air sent from a compressor (not shown) or the like is aseptically filtered by a vent filter 44 that has been sterilized in advance, and is supplied to the filtrate tank 4 as sterile air via a pipe 65. The liquid level of the injection in the filtrate tank 4 is pressed by the supply of the sterilized air, and the injection is not the pump, and the deepest part of the filtrate tank 4 having a complete discharge structure having a discharge port at the deepest part. From the part, it is transferred to the next process via the delivery main pipe 24.

  In the chemical compounding apparatus 1, the filtrate tank 4 is provided with a pressure gauge 46 (PIA of the filtrate tank 4 in FIG. 1), and its internal pressure is constantly monitored and when the pressure rises to a predetermined pressure or higher. Is judged abnormal, an alarm is issued, and the transfer of the injection solution by introducing sterile air into the filtrate tank 4 is stopped.

  In the chemical liquid blending apparatus 1, the steam and the cleaning liquid are introduced into the filtrate tank 4 through the pipe 67 branched from the introduction main pipe 23 and then into the introduction main pipe 22 and further through the branched pipe 66. The piping 66 is inserted into the filtrate tank 4 from the substantially central ceiling portion. A shower ball 45 is provided at the tip inside the filtrate tank 4.

  The steam and the surfactant supplied by the pipe 66 and the shower ball 45 are mainly used for cleaning or sterilizing the inside of the filtrate tank 4. The filtrate tank 4 is equipped with a thermometer 47 (TISA of the filtrate tank 4 in FIG. 1), the temperature of the steam is monitored, and an alarm is issued in the event of an abnormality such as the steam temperature being out of the specified range, and sterilization operation is performed. Is canceled.

  In the chemical liquid preparation device 1, the drainage liquid associated with cleaning or sterilization joins the drainage main pipe 81 and is discharged to the wastewater treatment (or sewage), but the secondary drainage from the aseptic filter 3 is blown. The pot 5 is cut off from the primary side drainage, so that the primary side drainage does not flow back to the secondary main communication pipe 22. That is, the primary drainage from the aseptic filter 3 is joined to the drainage main pipe 81 through the drainage pipe 83, the air vent pipe 86, and the drainage pipe 84 of the aseptic filter itself. As described above, the blow pot 5 is disposed at a position higher than the drainage main pipe 81, and the secondary side drainage fluid joins the drainage main pipe 81 via the drainage pipe 82 and the blowpot 5. Therefore, even if back pressure is applied when the drainage on the primary side joins the drainage main pipe 81, it returns to the air vent pipe 86 and drainage pipes 83, 84 or only enters the blow pot 5, There is no possibility of contamination from the drainage pipe 82 into the communication main pipe 22 and secondary contamination from the aseptic filter 3.

  By the way, in the chemical liquid preparation device according to the present invention, it is described that the aseptic filter can be configured in two stages in series, and an example thereof is shown in FIG. With reference to FIG. 7, the connection destination of the air vent pipe and the drainage pipe in the case of the above will be described. In accordance with the case of the first stage sterile filter, the air vent pipe of the first stage sterile filter and the drain pipe of the first stage sterile filter itself are connected to the drainage main pipe 81, and the second stage sterile filter The drainage pipe on the secondary side is connected to the blow pot 5. In order to maintain sterility, the air vent piping of the second stage sterile filter newly generated by making the sterile filter two stages and the drain pipe between the first stage and the second stage are connected to the blow pot 5. . On the other hand, the drainage pipe of the second-stage sterile filter itself is not used in the step of aseptically filtering the injection and does not need to maintain sterility, and is connected to the drainage main pipe 81.

  In the chemical liquid blending apparatus 1, the vent filter 48 provided in the blow pot 5 has a filter element made of PTFE (polytetrafluoroethylene) and PP (polypropylene) at least subjected to electrolytic polishing on the inner surface. It is housed in a stainless steel (SUS316L) housing (container), and the filtration accuracy is, for example, 0.2 to 0.45 μm. The drain main pipe 81 is provided with a thermometer 49 for monitoring the temperature of steam during sterilization of the pipes 21 and 22, the aseptic filter 3, the valves 51, 54, 55 and 56, the blow pot 5, and the vent filter 48. When the temperature of the steam is outside the specified range, an alarm is issued and the sterilization operation is stopped.

  In the chemical compounding apparatus 1, the valves 51, 54, 55, 56, and 57 provided in the communication main pipes 21 and 22 are all three-way valves, and the other valves frequently use three-way valves. The chemical compounding apparatus 1 uses two types of three-way valves, that is, the three-way valve shown in FIGS. 5 (a) and 5 (b) and the three-way valve shown in FIGS. 6 (a) and 6 (b). The former has a feature that the flow in the linear direction and the flow in the three directions can be switched, and the latter has a feature that the flow in the L-shape and the three directions can be switched. Can be used properly. As for switching of the valve, Japanese Patent Laid-Open No. 2003-207086 proposes a method of automatically switching the valve by rotating the turntable.

  In the chemical preparation apparatus 1, a three-way valve is frequently used, and at least the communication main pipes 21 and 22 are all made into three-way valves, thereby reducing a liquid pool derived from the valves. As shown in FIG. 2, when the valve around the sterile filter is a two-way valve, when liquid is passed as shown in FIG. 3, liquid reservoirs 101 and 102 are created in the pipe, as shown in FIG. When the liquid is passed through, the liquid reservoirs 103 and 104 are born in the pipe, which may contaminate the injection or cause the concentration of the target component of the injection to fluctuate. Such problems are unlikely to occur. In FIGS. 3 and 4, the thick line in the figure represents the pipe through which the liquid is passed.

  The chemical liquid preparation apparatus according to the present invention has been described above. Next, the chemical liquid preparation method according to the present invention will be described. The chemical solution preparation method according to the present invention is a method for obtaining an aseptic chemical solution having a target component adjusted to a predetermined concentration from a plurality of raw materials. In the following description, the chemical solution preparation device 1 shown in FIG. 1 is used. As a plurality of raw materials, water for injection and a liquid compound containing a certain medicinal component are mixed, and after aseptic filtration, a sterile injectable preparation whose target medicinal component is adjusted to a predetermined concentration ( This will be described as a method for obtaining a chemical solution.

  In the chemical solution preparation method according to the present invention, when the injection preparation is prepared using the chemical preparation device 1, the introduction main pipe 23 of the chemical preparation device 1 is used for each batch (for each injection preparation step). The bubbling nozzle 38, the shower ball 35, the shaft 31 of the stirrer, the drainage pipes 82 to 84, and the air vent pipe 86 are divided into a plurality of stages, and more preferably individually, for cleaning. And preferably, sterilization of the same portion is performed in a plurality of stages for each predetermined batch of preparation of the injection.

  Therefore, hereinafter, in addition to the preparation of the injection, the step of sterilizing each part will be described with reference to FIGS. In the sterilization, steam is used, but in the cleaning, except for using, for example, a cleaning solution instead of the steam, generally, the sterilization is performed, and thus the description of the cleaning is omitted. 9 to 16, the reference numerals and names are omitted, but FIGS. 9 to 16 are flowcharts showing the respective steps by the chemical liquid preparation device 1, and the following description is based on the reference numerals in FIG. 1. And using the name. 9-16, the thick line in a figure represents piping which a steam leads.

  First, an injection preparation process will be described. FIG. 9 and FIG. 10 are flowcharts showing the preparation process of an injection, FIG. 9 shows a filtration process that is a further subdivision of the preparation process, and FIG. 10 similarly shows a filtrate line air pushing process. Show.

  In the injection preparation process, before entering the filtration process (FIG. 9), water for injection is first introduced into the preparation tank 2 through the introduction main pipe 23 and the liquid introduction pipe 32, and the amount of the liquid is measured by the load cell 33. Is done. Next, the liquid compound is added by a predetermined amount while being measured by the load cell 33. And they are fully mixed by the stirrer of the preparation tank 2, and the injection which the medicinal component concerning a liquid compound became a predetermined density | concentration is obtained (a narrowly-defined preparation process).

  And the filtration process shown by FIG. 9 is performed. In the filtration step, aseptic air is introduced into the preparation tank 2 through the vent filter 34, thereby pressing the liquid level of the injection in the preparation tank 2, and the injection is discharged to the deepest part without using a pump. From the deepest part of the preparation tank 2 having a complete discharge structure, the liquid is sent to the sterilizing filter 3 through the communication main pipe 21, filtered through the sterilization filter 3 and sterilized, and filtrated through the communication main pipe 22. It is transferred to the tank 4.

  It is difficult to push the injection solution in the communication main pipe 22 that is the secondary side of the sterile filter into the filtrate tank 4 only by the filtration step. In addition, since the pressure applied to the secondary side is lowered due to the pressure loss of the filter element of the sterile filter, there is a situation that the preparation agent remains on the secondary side of the sterile filter more easily than the primary side. Then, subsequently, the filtrate line air pushing process shown in FIG. 10 is performed. In the filtrate line air pushing step, aseptic air is supplied from the filtrate tank 4 side to the communication main pipe 22 via the valve 77, and the injection solution in the communication main pipe 22 is completely pushed out to the filtrate tank 4, and the communication main pipe. No injection remains in 22. Then, the compressed air is sterilized through the vent filter 44 and introduced into the filtrate tank 4, whereby the liquid level of the injection in the filtrate tank 4 is pressed, and the injection is discharged to the deepest part without using a pump. From the deepest part of the filtrate tank 4 having a complete discharge structure with an outlet, it is sent to the next process (filling machine) via the delivery main pipe 24. That is, the injection preparation process starts from a state where no liquid is present in the system of the chemical liquid preparation apparatus, and finishes by sending out all the liquids in the system, and this one process is one batch. Needless to say, the injection preparation process is performed after the chemical compounding apparatus is sterilized by the sterilization process (and washing process) described below.

  Next, each sterilization process will be described. FIG. 11 is a flowchart showing the sterilization process of the introduction main pipe. In the sterilization process of the introduction main pipe, steam (sterilization steam) is introduced into the preparation tank 2 from the introduction main pipe 23 through the liquid introduction pipe 32 by the operation of the valves 53 and 52. By the process of this step, in addition to the introduction main pipe 23 and the liquid introduction pipe 32, the inside of the preparation tank 2 and the vent filter 34 attached to the preparation tank 2 are mainly sterilized.

  FIG. 12 is a flowchart showing a shower ball sterilization process. In the shower ball sterilization process, steam is introduced from the two shower balls 35 into the preparation tank 2 through the pipe 62 from the introduction main pipe 23 by operating the valves 53 and 72. By this process, in addition to the shower ball 35, the introduction main pipe 23, the pipe 62, the inside of the preparation tank 2, the shaft 31 of the stirrer, and the vent filter 34 attached to the preparation tank 2 are mainly sterilized. .

  FIG. 13 is a flowchart showing the sterilization process of the bubbling nozzle. In the bubbling nozzle sterilization step, steam (sterilization steam) is introduced from the bubbling nozzle 38 into the preparation tank 2 through the pipe 64 by the operation of the valves 53 and 74. By the process of this step, in addition to the bubbling nozzle 38, the introduction main pipe 23, the pipe 64, the inside of the preparation tank 2, and the vent filter 34 attached to the preparation tank 2 are mainly sterilized.

  FIG. 14 is a flowchart showing the sterilization process of the shaft of the stirrer. In the sterilization process of the stirrer shaft, steam (sterilization steam) is introduced from the main pipe 23 through the pipe 63 to the inside of the preparation tank 2 from the mounting portion of the stirrer shaft 31 by operating the valves 53 and 73. . By this process, in addition to the entire agitator including the attachment portion of the shaft 31, the introduction main pipe 23, the pipe 63, the inside of the preparation tank 2, and the vent filter 34 attached to the preparation tank 2 are mainly sterilized. The

  FIG. 15 is a flowchart showing the sterilization process of the air vent pipe. In the sterilization process of the air vent pipe, steam (sterilization steam) is discharged from the introduction main pipe 23 to the drainage pipes 82 and 83 and the communication main pipe by the operation of the valves 51, 53 to 56, 75 to 79, 91 to 93. 21, 22, pipes 67 and 68, air vent pipe 86, drainage main pipe 81, blow pot 5 (vent filter 48), and aseptic filter 3. By the process of this step, the drainage piping system including the air vent piping 86 of the aseptic filter 3 is mainly sterilized.

  FIG. 16 is a flowchart showing the sterilization process of the drainage pipe. In the sterilization process of the drainage pipe, steam (sterilization steam) is discharged from the introduction main pipe 23 to the drainage pipes 82 to 84 and the communication main pipe by operating the valves 51, 53 to 56, 75 to 79, 91 and 94. 21, 22, pipes 67 and 68, drainage main pipe 81, blow pot 5 (vent filter 48), and aseptic filter 3. By the process of this step, the drainage pipe system including the drainage pipe 84 of the aseptic filter 3 itself is mainly sterilized.

  The chemical liquid preparation device and the chemical liquid preparation method of the present invention are suitable as means for producing an injection. Furthermore, the chemical liquid preparation apparatus and chemical liquid preparation method of the present invention produce a predetermined preparation liquid (preparation liquid) that has high demands on the concentration accuracy of the target component and the viable bacteria removal level (sterility) that leads to generation of fine particles. It can be used as a means. Examples of such a preparation liquid include a cleaning liquid, a developing liquid, a peeling liquid, and the like that are used in manufacturing processes of semiconductors, liquid crystals, and other electronic components.

It is a flowchart which shows typically one Embodiment of the chemical | medical solution preparation apparatus which concerns on this invention. It is a flowchart around the aseptic filter for demonstrating the problem of the two-way valve in a chemical | medical solution preparation apparatus. It is a flowchart around the aseptic filter for demonstrating the problem of the two-way valve in a chemical | medical solution preparation apparatus. It is a flowchart around the aseptic filter for demonstrating the problem of the two-way valve in a chemical | medical solution preparation apparatus. Fig.5 (a) and FIG.5 (b) are figures which show an example of a three-way valve. FIG. 6A and FIG. 6B are diagrams showing other examples of the three-way valve. It is a flow figure around an aseptic filter when an aseptic filter is configured in two stages in series in the chemical liquid preparation device according to the present invention. FIG. 8A and FIG. 8B are flow charts around the sterile filter for explaining the use of sterile filters of different sizes in the chemical liquid preparation device according to the present invention. It is a flowchart which shows the filtration process which subdivided the preparation process of the chemical | medical solution preparation method which concerns on this invention further. It is a flowchart which shows the filtrate line air pushing process which subdivided the preparation process of the chemical | medical solution preparation method which concerns on this invention further. It is a flowchart showing the sterilization process of the introduction main piping of the chemical | medical solution preparation method which concerns on this invention. It is a flowchart showing the sterilization process of the shower ball of the chemical | medical solution preparation method which concerns on this invention. It is a flowchart showing the sterilization process of the bubbling nozzle of the chemical | medical solution preparation method which concerns on this invention. It is a flowchart showing the sterilization process of the shaft of the stirrer of the chemical | medical solution preparation method which concerns on this invention. It is a flowchart showing the sterilization process of the air vent piping of the chemical | medical solution preparation method which concerns on this invention. It is a flowchart showing the sterilization process of the drainage piping of the chemical | medical solution preparation method which concerns on this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Chemical liquid preparation apparatus, 2 ... Preparation tank, 3 ... Aseptic filter, 4 ... Filtrate tank, 5 ... Blow pot, 31 ... Shaft, 32 ... Liquid introduction pipe, 33 ... Load cell, 34 ... Vent filter, 35 ... Shower ball, 36 ... Pressure gauge, 37 ... Thermometer, 38 ... Bubbling nozzle, 39 ... Level switch, 40 ... Pressure gauge, 42 ... Liquid introduction pipe, 44 ... Vent filter, 45 ... Shower ball, 46 ... Pressure gauge, 47 ... Thermometer 48 vent filter 49 thermometer.

Claims (13)

A chemical preparation device that mixes a plurality of raw materials and sterilizes by filtration after the target component is adjusted to a predetermined concentration and obtains a chemical that needs to be aseptic.
A preparation tank for receiving the plurality of raw materials and mixing them at a predetermined ratio to obtain a preparation liquid;
A filter that is connected to the preparation tank through a communication main channel and performs aseptic filtration of the obtained preparation;
A filtrate tank connected to the filter through a communication main flow path and receiving the sterile-filtered preparation liquid, and
The liquid volume measurement means for measuring the amount of liquid in the material to preparation, comprising the preparation tank, Ri the liquid quantity measuring means, the load cell or a pressure gauge der,
An apparatus for preparing a liquid medicine , further comprising an air vent channel connected to the primary side of the filter itself, and a detector for detecting the presence or absence of air in the air vent channel .   Gas supply means for supplying aseptic gas to the preparation tank is further provided, and the liquid level of the preparation liquid in the preparation tank is pressed by the supply of the sterile gas to feed the filter from the preparation tank. The chemical | medical solution preparation apparatus of Claim 1 which carries out the aseptic filtration and transfer of the said preparation liquid to the said filtrate tank through this.   A gas supply means for supplying a sterile gas to a communication main flow path for connecting the preparation tank and the filter is further provided, and a communication main flow path for connecting the preparation tank and the filter by the supply of the sterile gas. The chemical solution blending device according to claim 1, wherein the preparation liquid remaining in the communication main flow path connecting the filter and the filter and the filtrate tank is pressed and fed to the filtrate tank. The preparation tank has a complete discharge structure with a discharge port at the deepest part,
The preparation tank, the filter, and the filtrate tank are installed so as to be lower in that order, and at least a communication main channel that connects the preparation tank and the filter, and the filter and the filtrate tank, The chemical | medical solution preparation apparatus as described in any one of Claims 1-3 formed with the gradient of 1/100 or more, respectively.   A gas supply means for supplying an inert gas used for deoxygenation of the raw material or the preparation liquid to the preparation tank is further provided, and the gas supply means is configured to bubbling at the end of the flow path entering the inside of the preparation tank. The chemical | medical solution preparation apparatus as described in any one of Claims 1-4 which provided the nozzle.   It further has a dedicated sterilization steam channel or cleaning liquid supply channel for supplying sterilization vapor or cleaning liquid used for sterilization or cleaning inside the preparation tank to the preparation tank, and is provided inside the preparation tank. The chemical | medical solution preparation apparatus as described in any one of Claims 1-5 which provided the shower ball in each front-end | tip of the vapor | steam path | route for exclusive use sterilization thru | or the washing | cleaning liquid supply flow path to enter.   A stirrer for performing the mixing is further provided in the preparation tank, and a sterilization steam channel or cleaning liquid supply dedicated for supplying sterilization steam or cleaning liquid used for sterilization or cleaning of the shaft of the stirrer to the preparation tank The chemical | medical solution preparation apparatus as described in any one of Claims 1-6 which has a flow path.   The communication main flow path connecting the preparation tank and the filter, and the filter and the filtrate tank is further provided with a valve for branching the communication main flow path, and at least the valve is a sanitary diaphragm valve. It is a three-way valve, The chemical | medical solution preparation apparatus as described in any one of Claims 1-7. And further having a plurality of drainage channels branched from a communication main channel connecting the preparation tank and the filter, and the filter and the filtrate tank, and the plurality of drainage channels are connected to the filter. The chemical | medical solution preparation apparatus as described in any one of Claims 1-8 interrupted | blocked by the means which can be interrupted | blocked so that it may not communicate directly with a primary side and a secondary side. It said filter to provide a connection to the flow path of a predetermined adapter, chemical formulation according to any one of claim 1 to 9, which allows using different filter sizes. A preparation tank that receives a plurality of raw materials and mixes them at a predetermined ratio to obtain a preparation liquid, a filter that is connected to the preparation tank through a communication main channel, and filters the obtained preparation liquid aseptically, and the filter And a filtrate tank that is connected by a communication main flow path and receives the sterile filtered preparation liquid,
An introduction main channel for introducing the raw material into the preparation tank, a gas supply means for supplying an inert gas used for deoxygenation of the raw material or the preparation liquid to the preparation tank, and the gas supply means constituting the preparation tank A bubbling nozzle provided at the tip of a flow path that enters the interior of the tank, and a sterilization steam flow path for supplying sterilization steam or cleaning liquid used for sterilization or cleaning inside the preparation tank to the preparation tank A cleaning liquid supply channel, a dedicated sterilization vapor channel or a cleaning liquid supply channel that enters the inside of the preparation tank, a shower ball provided at the tip of each, a stirrer that is provided in the preparation tank and performs the mixing, Connected to the primary side of the filter itself, the communication main flow path connecting the preparation tank and the filter, the filter and the filtrate tank, a plurality of drainage flow paths branched from the communication main flow path Air vent channel , And by using a chemical solution preparation apparatus further comprising,
A chemical liquid preparation method for obtaining an aseptic chemical liquid in which target components are adjusted to a predetermined concentration from a plurality of raw materials,
Cleaning at least one batch of the preparation tank, the filter, the filtrate tank, the introduction main flow path, the bubbling nozzle, the shower ball, the shaft of the stirrer, the drainage flow path, and the air vent flow path. A chemical compounding method that is performed in multiple stages for each stage. At least, the introduction main passage, the bubbling nozzle, the shower ball, the stirrer shaft, the drainage flow path, and the cleaning of the air vent channels, each one batch, individually, claim performed separately 11 The chemical | medical solution preparation method of description. At least a plurality of stages of sterilization of the introduction main flow path, the bubbling nozzle, the shower ball, the shaft of the stirrer, the drainage flow path, and the air vent flow path every predetermined batch or every predetermined period 13. The method for preparing a chemical solution according to claim 11 or 12 , which is performed separately.

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