JP2015189515A - Liquid adjustment device and liquid dispensation system - Google Patents

Abstract

PROBLEM TO BE SOLVED: To solve a problem in that, in order to prepare a medicine in an environment where cleanliness is ensured in an arbitrary place other than an aseptic manipulation area without requiring the introduction or expansion of an aseptic manipulation area and pharmaceutical equipment, it is necessary to inject a liquid medicine into a closed container and measure the quantity of injected medicine, while preventing contamination of the interior of the container with germs or the line; however, a conventional device requires the pulling in/out of an injection needle and the opening/closing of a lid, which make it difficult to prevent contamination with germs or the like unless in an aseptic operation area.SOLUTION: As one aspect of the present invention to solve at least one of the problems described above, a liquid adjustment device is provided with a measuring unit that measures with a container connected to pipes, when a liquid in a first container and a second liquid in a second container are mixed in a third container via the pipes.

Description

  The present invention relates to a technique for adjusting a liquid by measuring a liquid amount in a container. In particular, the present invention relates to a technique for adjusting the liquid by measuring the amount of liquid injected into the container in a state where the flow path pipe is connected.

The chemical solution used for diagnosis by PET (positron emission tomography) is a radionuclide in FDG (fluorodeoxyglucose) by utilizing the property that cancer cells take 3 to 8 times more glucose than normal cells. ¹⁸ radiopharmaceutical such as ¹⁸ F-FDG incorporating F is used. The radionuclide used for PET diagnosis has a short half-life, and the half-life of ¹⁸ F is about 110 minutes. For this reason, it is necessary to use the radiopharmaceutical within a short time after the preparation of the radiopharmaceutical. Moreover, since the chemical | medical solution used for a diagnosis is administered to a test subject, it must be aseptic.

  Therefore, in the preparation of radiopharmaceuticals, the radioactive drug substance and non-radioactive diluent are mixed in a sterile operation area near the PET diagnostic equipment in hospitals, etc. Aseptically fill the container. At this time, an injection amount of a chemical solution or the like is measured as a weight and adjusted to a designated radioactivity amount.

  Here, when measuring the weight of the chemical solution or the like injected into the container, when the container is covered and measured, for example, as shown in Patent Document 1, the container and the tare of the lid are measured in advance. The weight can be measured after the injection, and the injection amount can be determined from the value obtained by subtracting the tare.

  In order to maintain aseptic conditions, when using a container such as a vial whose mouth is closed with a rubber stopper or the like, for example, as shown in Patent Document 2, the weight of a container containing a chemical solution or the like is measured in advance. Then, after the needle is inserted into the rubber stopper of the container and sucked, the needle is removed and the weight is measured, and the amount injected outside can be determined from the reduced value.

Japanese Patent No. 4399588 JP2013-160615A

  It is not easy to introduce or expand the above-described aseptic operation area or pharmaceutical facility in the vicinity of the PET diagnostic apparatus. In order to prepare drugs in an environment where cleanliness is ensured in any area other than the aseptic operation area without requiring the introduction or expansion of such aseptic operation area and pharmaceutical equipment, the inside of the container is contaminated with bacteria. It is necessary to inject the chemical into a sealed container and measure the injection amount.

  However, in the technique of injecting into a container for opening and closing the lid as disclosed in Patent Document 1 and the technique of inserting and removing the injection needle as disclosed in Patent Document 2, contamination by bacteria or the like is required unless it is an aseptic operation area. It becomes difficult to prevent.

  In view of the above problems, an object of the present invention is to perform liquid injection into a sealed container and highly accurate injection amount measurement while preventing the inside of the container from being contaminated by bacteria or the like.

  As one embodiment of the present invention for solving at least one of the above-described problems, a liquid in the first container and a second liquid in the second container are connected to the third through a pipe. When mixing in the container, the liquid adjusting device is provided with a measuring unit for measuring in a state where the container is connected to the pipe.

  According to the present invention, it is possible to perform liquid injection into a sealed container and highly accurate injection amount measurement while preventing the inside of the container from being contaminated by bacteria or the like. Problems, configurations, and effects other than those described above will be clarified by the following description of embodiments.

The system block diagram which shows the structural example of the liquid dispensing system of this invention. The apparatus block diagram which shows the structural example of the liquid adjustment apparatus of the liquid dispensing system of this invention. The flowchart which shows operation | movement of the liquid dispensing system of this invention. The block diagram which shows the structural example of the weight measuring apparatus in the liquid dispensing system of this invention. Sectional drawing which shows the structural example of the weight measuring apparatus in the liquid dispensing system of this invention. The block diagram which shows the structural example of the disposable kit of a mixing part. The block diagram which shows the structural example of the disposable kit of a dispensing part. The block diagram which shows the example of shaping | molding of spring piping. The graph which shows the result of the experiment example of this invention. The graph which shows the other result of the experiment example of this invention. The graph which shows the other result (3 windings) of the experiment example of this invention. The graph which shows the other result (4 windings) of the experiment example of this invention. The graph which shows the relationship between the spring constant in the experiment example of this invention, weight, and the number of coil turns. The block diagram which shows the other example of a shaping | molding of spring piping.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

  FIG. 1 is a system configuration diagram showing a configuration example of a liquid dispensing system according to an embodiment of the present invention. The liquid dispensing system in the present embodiment is a closed system dispensing system that dispenses a chemical solution such as a PET drug while ensuring sterility. The closed system dispensing system includes a mixing unit 100 that mixes liquids and adjusts the liquid, a dispensing unit 200 that dispenses the adjusted liquids, and a control unit 300 that controls them. A portion surrounded by a dotted line is the liquid supply unit 400. Although not shown in the figure, these are housed in a chamber that protects against radiation.

  In the closed system dispensing system in the present embodiment, the radioactive drug substance solution that emits strong radiation in the mixing unit 100 is mixed with the diluent and the radioactivity is adjusted to prepare the synthesis drug 109 in the synthesis container 109. 109 is dispensed into the individual container 201 by the dispensing unit 200. A filter 202 that ensures sterility is disposed in the radioactive chemical liquid inlet channel connected to the mixing unit 100 of the dispensing unit 200. Other similar filters can be arranged.

  The details of the mixing unit 100 of the closed system dispensing system of FIG. 1 will be described with reference to FIG. The mixing unit 100 is a liquid adjusting device that includes a piping system up to the stage before dispensing into the individual containers 201 in the dispensing unit 200 of FIG. 1, and mixes a diluted solution with the radiopharmaceutical drug solution to obtain a desired radiation. It is the structure which adjusts dilution to capacity.

  The mixing unit 100 includes a drug substance intake port 101, a purge nitrogen gas intake port 102 in the pipe, an outlet 103 for sending the drug whose concentration has been adjusted to the individual dispensing pipe which is the next step, and a drug substance recovery container 104. , Dilution liquid container 105, dilution liquid recovery container 106, two types of syringe pumps 107 for sucking and discharging the recovered radiopharmaceutical drug substance and dilution liquid in the pipe, waste liquid recovery container 108, synthesis container 109, and other waste liquid recovery A container 110, a plurality of three-way cocks 111, and a plurality of pipes 112 are provided.

  The drug substance recovery container 104, the dilution liquid container 105, the dilution liquid recovery container 106, the waste liquid recovery container 108, the synthesis container 109, and the other waste liquid recovery containers 110 are sealed containers having stoppers at the openings. Then, an example is shown in which a glass vial with a rubber stopper into which an injection needle can be inserted and removed is used. Among these sealed containers, the drug substance recovery container 104 and the synthesis container 109 are placed on the weight measuring unit 113, and the radioactive liquid discharged into the drug substance recovery container 104 and the synthesis container 109 are stored in the container. Measure the weight. A radiation detector 114 is disposed in the vicinity of the weight measuring unit 113 and measures the radioactivity of the radioactive liquid discharged into the drug substance recovery container 104 and the synthesis container 109.

  The drug substance recovery container 104 and the synthesis container 109 placed on the weight measuring unit 113 have a spring property such as a spring constant in the direction of the weight measuring unit 113 having a shape as shown in the spring piping 120, for example. It is connected to the spring piping. The spring constant of the spring pipe 120 is measured in advance, and measurement is performed based on the spring constant. The configuration of the spring piping 120 and the effect thereof will be described later with reference to FIGS.

  In FIG. 2, each three-way cock 111 is indicated by a symbol in which three triangles face each other in a circle, and the three opposite triangles rotate in the circle, and only in the direction corresponding to the pipe 112. Are shown to circulate inside. There are twelve three-way stopcocks 111 shown in FIG. 2 from BV-0 to BV-2, and SV-0 to SV-8, and there are a plurality of dispensing parts 200 that are the next step not shown in FIG. It is used.

  Here, in FIG. 2, the drug substance intake port 101, the nitrogen gas intake port 102, the outlet 103, the drug substance solution recovery container 104, the dilution solution container 105, the dilution solution recovery container 106, the syringe pump 107, the waste solution recovery container 108, and the synthesis container. 109 and each of the waste liquid collection containers 110 are connected by a plurality of pipes 112 through three-way cocks 111 in a state in which sterility is ensured. As described above, the operation of the closed system dispensing system is executed in an arbitrary area other than the aseptic operation area in a connected state in which the flow path and the container in the mixing unit 100 and the dispensing unit 200 ensure sterility. The

  Therefore, the parts shown in the mixing unit 100 in FIG. 2 and the parts used in the dispensing unit 200 are disposable kits that have been sterilized to prevent infection, as will be described later with reference to FIGS. 6A and 6B. Supplied, used once to several times, and attached to the closed dispensing system before starting operation. Although not shown in the figure, filters that ensure sterility are attached to a plurality of locations of the piping 112, and all containers except the diluent container 105 are provided with vent filters that ensure sterility.

  Below, the structure of the disposable kit of the mixing part 100 and the dispensing part 200 which were sterilized in order to prevent infectious diseases in the present embodiment will be described. In the disposable kit of the present embodiment, the disposable piping inside the container and each container are connected in a state of being aseptically packed. Then, the pack is opened, and the connection side of the piping to the nucleosynthesis device side is connected to the radionuclide nucleosynthesis device. A filter that ensures sterility is disposed at the connection port of the piping with the nucleosynthesis apparatus side, and these operations can be performed outside the aseptic operation area. Hereinafter, an example of the disposable kit in the present embodiment will be described in detail with reference to FIGS. 6A and 6B.

  First, FIG. 6A shows a configuration example of a disposable kit of the mixing unit 100. As shown in FIG. 6A, the disposable kit of the mixing unit 100 includes a plurality of three-way stopcocks 111, two types of syringes 150 attached to the syringe pump 107 shown in FIGS. 1 and 2, a syringe 151, and a drug substance recovery container 104. , A diluent storage container 106, a waste liquid recovery container 108, a synthesis container 109, and a waste liquid recovery container 110, and holders that can be stored while maintaining their respective positions in a state where they are connected by a pipe 112 or a spring pipe 120. 152 and is hermetically packaged by a package 1521 in a sterilized state. Further, there is a joint 153 at the connection end of the disposable kit that becomes the drug substance intake port 101, the nitrogen gas intake port 102, and the outlet 103.

  When using the disposable kit of the mixing unit 100, the sterile package 1521 is opened in the vicinity of the main body of the closed system dispensing system and attached to the main closed system dispensing system main body, and the joint 153 is connected to the closed system dispensing system main body. After connecting to the side, the holder 152 is removed.

  Next, FIG. 6B shows a configuration example of the disposable kit of the dispensing unit 200. As shown in FIG. 6B, the disposable kit of the dispensing unit 200 maintained the positions of the pipe 112, the plurality of three-way cocks 111 connected by the pipe 112, the filter 202, and the plurality of individual containers 201. It is comprised from the holder 154 which can be stored as it is. A joint 153 is provided at the connection end of the disposable kit with the outside. Further, the lid of the individual container 201 is made of a resilient material such as rubber, and is closed when the pipe is removed.

  When using the disposable kit of the dispensing unit 200, first, the sterile package 1541 is opened and attached to the closed system dispensing system body in the vicinity of the closed system dispensing system body, and the joint 153 is installed in the closed system dispensing system. After connecting to the main body side, the holder 154 is removed.

  In the above, the whole structure of the closed system dispensing system in a present Example has been demonstrated using FIG.1, FIG.2, FIG.6A and FIG. 6B.

  Below, operation | movement of the closed system dispensing system in a present Example is demonstrated. FIG. 3 is a flowchart showing the operation of the closed system dispensing system under the control of the control unit 300. The three-way stopcock 111 rotates and switches each time in accordance with the control of the control unit 300.

  When the operation is started, the radiopharmaceutical drug substance solution is introduced into the pipe 112 from the drug substance intake port 101, and into the drug substance solution collection container 104 via the BV-0, SV-0, SV-1 in the three-way stopcock 111. Collect (301). The weight of the radiopharmaceutical drug substance collected in the drug substance collecting container 104 is measured by the weight measuring unit 113 (302). Next, the radioactivity concentration of the radiopharmaceutical drug substance recovered in the drug substance recovery container 104 by the radiation detector 114 is measured (303). From the product of the measured weight of the radiopharmaceutical drug substance and the concentration of radioactivity, the amount of radioactivity of the entire radiopharmaceutical drug substance recovered in the drug substance recovery container 104 is calculated (304).

  Next, in order to purge the radiopharmaceutical drug substance remaining in the pipe 112 in the above process, nitrogen gas is introduced into the pipe from the nitrogen gas intake port 102 and BV-1, BV-0, SV of the three-way cock 111 It is collected in the waste liquid collection container 108 via -0 (305).

  After collecting the radiopharmaceutical drug substance in the drug substance recovery container 104 or in parallel processing, nitrogen gas is introduced into the diluent container 105 from the nitrogen gas intake port 102 via the BV-1 and BV-2 of the three-way stopcock 111, and the pressure Then, the diluent in the diluent container 105 is transferred to the diluent collection container 106 via SV-3 of the three-way stopcock 111 (306).

  Next, a predetermined amount of the radioactive drug substance solution in the drug substance recovery container 104 is sucked into the syringe pump 107 through the SV-1, SV-2, SV-4, SV-5 of the three-way stopcock 111. (307). Subsequently, the entire amount of the radiopharmaceutical drug substance sucked into the syringe pump 107 is discharged to the synthesis container 109 via the SV-5, SV-6, SV-7 of the three-way stopcock 111 (308).

  The capacity sucked from the drug substance recovery container 104 at this time is the sum of the capacity sucked into the syringe pump 107 and the capacity remaining in the pipe 112 from the syringe pump 107 to the drug substance recovery container 104. The volume discharged into the syringe is the sum of the volume sucked into the syringe pump 107 and the volume remaining between the syringe pump 107 and the SV-5 of the three-way cock 111. A slight amount of gas such as nitrogen gas is sucked into the syringe pump 107 in advance in order to discharge the entire amount of the radiopharmaceutical drug substance sucked into the syringe pump 107 and a diluent described later.

  The weight of the radiopharmaceutical drug substance discharged into the synthesis container 109 is measured by the weight measuring unit 113 (309), and the radioactivity concentration is measured by the radiation detector 114 (310). Then, from the product of the measured weight of the radiopharmaceutical drug substance and the concentration of radioactivity, the radioactivity amount of the entire radiopharmaceutical drug substance recovered in the drug substance recovery container 104 is determined (311).

  After discharging and collecting a predetermined amount of the radiopharmaceutical drug substance into the synthesis container 109, nitrogen gas is introduced into the pipe 112 from the nitrogen gas intake port 102, and BV-1, BV-2, SV-8, SV-7, It flows into the waste liquid recovery container 110 via SV-6, SV-5, SV-4, and SV-2, and the radioactive drug substance solution remaining in the pipe 112 is purged and recovered in the waste liquid recovery container 110 (312). ).

  Next, a predetermined amount of the diluent in the diluent collection container 106 is sucked into the syringe pump 107 via the SV-4 and SV-5 of the three-way stopcock 111 (313). Subsequently, the entire amount of the diluted solution sucked into the syringe pump 107 was discharged to the synthesis container 109 via the SV-5, SV-6, and SV-7 of the three-way stopcock 111, and was previously collected in the synthesis container 109. It is mixed with a radiopharmaceutical drug substance solution to obtain a radiopharmaceutical having a specified radioactivity (314). At this time, the predetermined amount of dilution liquid is calculated in order to make the radiopharmaceutical solution a specified radioactivity amount based on the radioactivity of the entire radiopharmaceutical drug substance discharged to the previously determined synthesis container 109. The volume of dilution liquid. The capacity sucked from the diluent collection container 106 is the sum of the capacity sucked into the syringe pump 107 and the capacity remaining in the pipe 112 from the syringe pump 107 to the diluent collection container 106, and is discharged to the synthesis container 109. The volume to be discharged is the sum of the volume sucked into the syringe pump 107 and the volume remaining between the syringe pump 107 and the SV-5 of the three-way stopcock 111. Can be calculated.

  Subsequently, the weight of the radiopharmaceutical solution obtained by mixing the radiopharmaceutical drug substance and the diluent is measured by the weight measuring unit 113 (315), the radioactivity concentration is measured by the radiation detector 114 (316), and the radioactivity is again radioactive. The amount of radioactivity of the entire drug solution is determined (317).

Then, it is confirmed whether or not the radioactivity amount of the radioactive drug solution is within the specified radioactivity amount (318). If the radiopharmaceutical solution is not within the specified amount of radioactivity, if the concentration is higher than the specified amount of radioactivity, repeat steps 313 to 317 and perform dilution again, so that the radiochemical solution reaches the specified amount of radioactivity. Adjust to fit.
And if it can confirm that the radioactive chemical solution was settled in the designated radioactivity amount, nitrogen gas will be introduce | transduced in the piping 112 from the nitrogen gas intake port 102, BV-1, BV-2, SV-8, SV-7, SV It flows to the waste liquid collection container 110 via −6, SV-5, SV-4, and SV-2, and the diluent remaining in the pipe 112 is purged and collected in the waste liquid collection container 110 (319).

  In step 318, when the concentration is extremely lower than the designated radioactivity amount (for example, less than a prestored threshold), the processing of steps 313 to 317 is performed again, and the radioactive drug solution is adjusted to the designated radioactivity amount. Adjustments can be made to fit.

  Then, in the dispensing unit 200 of the closed system dispensing system, the three-way cock 111 is rotated and switched under the control of the control unit 300, and the radioactive chemical prepared in the synthesis container 109 is dispensed into the individual container 201 (320). Here, the operation at the time of dispensing will be briefly described with reference to FIG.

  When the dispensing operation is started, the radiochemical solution adjusted in the synthesis container 109 in the above process is sucked into the syringe pump 107 through the SV-5, SV-6, SV-7 of the three-way cock 111. Subsequently, the entire amount of the radioactive chemical solution sucked into the syringe pump 107 is discharged to the individual container 201 via the SV-5, SV-6, SV-7, SV-8, and PV-0 of the three-way cock 111.

The capacity sucked from the synthesis container 109 at this time is the sum of the capacity sucked into the syringe pump 107 and the capacity remaining in the pipe 112 from the syringe pump 107 to the synthesis container 109, and is discharged to the individual container 201. The capacity is the sum of the capacity sucked into the syringe pump 107 and the capacity remaining between the syringe pump 107 and the SV-7 of the three-way cock 111. In addition, in order to discharge the whole amount of the radioactive chemical liquid sucked into the syringe pump 107, a slight amount of gas such as nitrogen gas is sucked into the syringe pump 107 in advance.
The above description of the operation at the time of dispensing is an explanation when dispensing to the individual container 201 connected to PV-0 via PV-0 of the three-way cock 111 of the dispensing unit. Thereafter, the dispensing operation is similarly performed on the individual containers 201 connected to the PV-1 to PV-5 of the three-way cock 111. In that case, the three-way stopcock 111 between them is rotated so that the individual containers 201 and the SV-8 of the three-way stopcock 111 communicate with each other, thereby enabling a dispensing operation.

  The operation of the closed system dispensing system in the present embodiment has been described above. Below, the detail of the weight measurement part 113 described in step 302,309,315 in the closed system dispensing system of a present Example is demonstrated.

  The drug substance collection container 104 and the synthesis container 109 use glass vials with rubber stoppers that allow insertion and removal of injection needles. The drug substance collection container 104 and the radioactive drug solution in the synthesis container 109 must be sterile because they are administered to the subject when used for diagnosis. The flow path is connected in a state in which sterility is ensured, and in that state, it is difficult to accurately measure the weight of the liquid discharged into the container due to the influence of the connected flow path.

  Therefore, in this embodiment, as shown by the spring pipe 120 in FIG. 2, the pipe connected to the container in advance has a spring property, and the measurement is made possible by optimizing the spring constant of the pipe.

  4 and 5 show an outline of a weight measuring device provided in the mixing unit 100 which is a liquid adjusting device of the closed system dispensing system in the present embodiment.

  FIG. 4 shows a part extracted from the mixing unit 100 of FIG. 2 and shows the weight measuring unit 113 in more detail. FIG. 5 shows the weight measuring unit 113 in a three-dimensional view and shows the lead shield 125 in cross section. 4 and 5 show an example in which the weight measurement unit 113 measures the weight of the drug substance recovery container 104, but the weight measurement unit 113 on the synthesis container 109 side is the same.

  In FIG. 4, only the SV-1 of the three-way stopcock 111 and the pipe 112 are shown in the liquid supply section 400, and one of the three connection ports of the SV-1 of the three-way stopcock 111 is connected to the drug substance recovery container by the pipe 112. 104 is connected. The drug substance recovery container 104 is a glass vial with a rubber stopper 115 into which an injection needle can be inserted and removed, and a pipe 112 includes a spring pipe 120, and an injection needle 116 is provided at the tip penetrating the rubber stopper 115. Is connected to the drug substance recovery container 104 by a connecting portion 117 having

  One of the pipes 112 connecting the SV-1 of the three-way stopcock 111 and the drug substance recovery container 104 is fixed to the liquid supply unit 400 by the fixing unit 119 after the SV-1 of the three-way stopcock 111, and the other Is fixed to the connecting portion 117. The pipe 112 is formed into a spring pipe 120 between the fixing part 119 and the connection part 117, and the weight change applied to the drug substance recovery container 104 during the suction and discharge of the radioactive drug substance to the drug substance recovery container 104 is fixed. Transmission to the part 119 is absorbed by the spring nature of the spring piping 120.

  In addition to the pipe 112, a vent filter 118 having an injection needle that penetrates the rubber stopper 115 is attached to the drug substance recovery container 104. The vent filter 118 ensures sterility, and plays a role of releasing the pressure change inside the drug substance recovery container 104 during the suction and discharge of the radioactive drug substance with respect to the drug substance recovery container 104. In addition, a vent filter that ensures sterility is attached to all containers except the diluent container 105 with the same structure.

  As shown in FIGS. 4 and 5, the drug substance recovery container 104 is placed on the weight measuring unit 113 and measures a change in its weight. The weight measuring unit 113 is fixed to the weight measuring unit 121 and the weight measuring unit of the weight measuring unit 121, and when viewed from the plane, three or four (four in FIG. 5) radial arms come out from the center. 2 plates 122, two plates 122 that connect the two plates 122 up and down, the same number of pillars 123 as the arms, and a holder 124 that holds the drug substance collection container 104 fixed on the upper plate 122. .

  Since the weight measuring device 121 in the weight measuring unit 113 of the present embodiment may cause an error in measurement accuracy when the internal weight measuring sensor 129 is irradiated with radiation, the drug substance collecting container 104 and the weight measuring device 121 may be affected. The lead shield 125 is disposed between the lead shield 125 and the radiation from the radiopharmaceutical drug substance solution in the drug substance recovery container 104 of the lead shield 125 is directly applied to the weight measuring sensor 129 in the weight measuring device 121. A through-hole 126 is opened at a position where it is not, so that the pillar 123 passes through the through-hole 126. In addition, a lead shield 127 is disposed above the lead shield 125 to prevent the radiation from the radiopharmaceutical drug substance solution in the drug substance recovery container 104 from being radiated to the outside, as indicated by phantom lines in FIG. The radiation detector 114 is disposed therein. The lead shield 125 is supported by a pillar 128. The liquid supply unit 400 and the weight measuring device 121 are connected by a rigid body.

  Next, the discharge weight measurement of the closed system dispensing system by the weight measuring unit 113 will be described in more detail. As a material of the pipe 112 provided with the spring pipe 120, moldable resin, metal, glass or the like can be used.

  Here, in the case where ethyl alcohol is contained in the radiopharmaceutical drug substance solution, dilution liquid, and radiopharmaceutical mixed with the radiopharmaceutical drug substance liquid and dilution liquid to be used, the material of the pipe 112 is tetrafluoride. Ethylene resin (hereinafter referred to as PTFE) is preferred. Further, when the liquid supply unit 400 is a disposable kit that can be used once or several times, from the viewpoint of waste disposal, a resin such as PTFE is used as the material of the pipe 112 compared to the metal or glass pipe. It is preferable to use it. In addition, a pipe made of PTFE is harder than a silicone rubber pipe or the like. However, even when a resin is used, it is not limited to PTFE, and other fluororesins and resins with little elution of components can also be used.

  Further, the material of the pipe 112 and the spring pipe 120 may be metal or glass. However, when using metal or glass, the spring constant becomes large at the same size, and it is necessary to increase the number of turns or increase the winding diameter in order to reduce the spring constant until accurate measurement is possible. Therefore, it should be noted that the internal dead volume becomes large. It is also possible to reduce the spring constant by reducing the inner and outer diameters of the piping. However, the resistance of the liquid flowing inside increases, and in order to flow the same amount, it is necessary to increase the pressure or take a longer time.

  In addition, the shape of the spring pipe 120 is not limited to the coiled spring pipe 120 as shown in FIG. 2 in the present embodiment, and for example, a weight measuring unit 113 as shown in FIGS. Other shapes having spring properties such as a spring constant in the direction are also possible. By setting it as these shapes, shaping | molding becomes easy rather than making it coil shape depending on a material. In addition, space saving in the three-dimensional direction can be realized by two-dimensional molding. On the other hand, when the spring pipe 120 is coiled, the liquid such as the radiopharmaceutical drug substance that passes through the spring pipe 120 does not move against gravity, so the direction in which the weight of the liquid that passes through is generated is partially Therefore, it is possible to prevent a region where the amount passing through the pipe is not proportional to the measured value.

  Below, the experimental example which examines beforehand about the influence with respect to the measurement precision of the characteristic of the spring which the spring piping 120 has is shown using FIGS. 7-12. In this experimental example, since examination by the number of windings is easy, an example examined using a coiled spring pipe is shown.

  In this experimental example, the amount of liquid discharged to the drug substance recovery container 104 and the synthesis container 109 is 2 to 10 ml, and the accuracy required for measuring the volume is ± 0.6%. In addition, the weight of the drug substance recovery container 104 and the synthesis container 109 is about 36 g, and it is assumed that a liquid having a weight of 2 g to 10 g is discharged into about 36 g and measured with an accuracy of ± 0.6%. .

  The PTFE spring pipe shown in FIG. 7 is molded by changing the number of turns of the coil, one is connected to the same vial as the drug substance recovery container 104, the other is connected to a syringe pump, and further shown in FIG. Thus, the accuracy at the time of discharging 10 ml due to the difference in the number of windings was measured so that the central axis of the coil was vertical.

  The results are shown in FIG. 8 and FIG. FIG. 8 shows a case where 10 milliliters are discharged all at once, and FIG. 9 shows a case where 10 milliliters are discharged 20 times. When the error at the time of three discharges was measured, under the conditions shown in FIG. 7, when 10 ml was discharged at once, the discharge error of 3 and 4 turns was small, and 10 ml was divided into 20 discharges. In this case, there was little discharge error of 4 windings.

  Next, using the three- and four-coiled coiled spring pipes 120 that had good accuracy in this measurement, it was measured how far the discharge amount could be reduced while maintaining the discharge accuracy at ± 0.6%. The results are shown in FIG. 10 and FIG. As a result, with the coiled spring piping of 3 turns, the accuracy could be kept at ± 0.6% even when the discharge amount was reduced to 2 ml, but when the discharge amount became 1 ml, the accuracy was ± 0. It was not possible to keep it at 6%. In addition, with the four-coil coil spring piping, the accuracy could be maintained at ± 0.6% even when the discharge amount was reduced to 1 milliliter.

  From the above results, when the spring pipe 120 used in the present embodiment is coiled, the inner diameter is 0.96 mm, the outer diameter is 1.56 mm, the average coil diameter is about 16 mm, and the number of turns is 4 under the above experimental conditions. It has been found that molding is most suitable.

  Here, the reason why the preferable condition of the coiled spring pipe 120 used in this embodiment is the above condition will be described below. The following is an example of the main mechanical properties of PTFE.

E: Flexural modulus = 0.55 GPa
ν: Poisson's ratio = 0.46
G: transverse elastic modulus = E / (2 (1 + ν)) = 0.188 GPa
ρ: specific gravity = 2.14
Moreover, the dimension of the piping 112 used in a present Example and a coil average diameter are as follows.

di: Piping inner diameter = φ0.96 mm
do: piping outer diameter = φ1.56 mm
D: Coil average diameter: φ16mm
FIG. 12 shows the results of obtaining the spring constant and weight of the spring piping 120 and the weight of the liquid (assuming water) inside the spring piping from the above data by varying the number of turns. 8, 9, and 12, in FIGS. 8 and 9, the approximate curve of the discharge error for each number of windings appears to draw a curve with 3 or 4 windings as the lowest point. . In FIG. 12, a straight line indicating the weight of the coiled spring pipe and the total weight of the liquid inside intersects with a curve indicating the spring constant of the coiled spring pipe in the vicinity of four turns. From this, in order to obtain the force necessary for extending and retracting the winding pitch of the coiled spring piping by 1 mm, the weight of the spring piping and the total weight of the liquid inside, and to expand and contract the winding pitch of the spring piping by 1 mm It is considered good to shape the spring piping so that the required force is the same as or slightly larger than the total weight. When obtaining the spring constant of the coil spring, PTFE, which is a resin, has a small linear range of stress and strain, so it is difficult to define the Young's modulus, so the bending elastic modulus was substituted.

  When the disposable kit including the coiled spring pipe 120 according to this embodiment is attached, the coil winding pitch slightly changes between the spring pipe 120 before the attachment and the spring pipe 120 after the attachment. Therefore, if it is attached so that the winding pitch is larger than before attachment, a tensile force is generated in the spring, and the weight of the drug substance recovery container 104 is displayed lightly. On the other hand, if the winding pitch is reduced, an extension force is generated in the spring, and the weight of the drug substance recovery container 104 is displayed heavy. However, due to the creep phenomenon of PTFE, which is a resin, the size of the pipe 112 of this embodiment is stabilized in a few minutes. After stabilization, the radioactive drug substance solution is discharged into the drug substance recovery container 104. When the radioactive drug substance solution passes through the spring pipe 120 during the discharge, a creep phenomenon occurs due to the weight of the liquid. An error is generated. The above-described preferred conditions regarding the coiled spring piping are the results including the error.

  In this way, by considering in advance the spring constant, weight, and weight inside the pipe of the spring pipe 120, the weight measurement accuracy can be improved by reflecting the weight when measuring the weight.

  If the piping 112 does not have the spring piping 120 and is connected linearly between the fixed portion 119 and the connecting portion 117, even if the liquid enters and exits the drug substance recovery container 104, it is connected linearly. The piping 112 thus pulled pulls up or pushes the drug substance recovery container 104, and the weight change cannot be measured accurately. On the other hand, in the present embodiment, the properties of the spring such as the spring constant are grasped in advance, and the spring pipe 120 is provided to absorb the pulling-up or pressing force depending on the nature of the spring, and measure with high accuracy. Make it possible.

  As described above, in this embodiment, by measuring the weight in a sealed state where the pipe is connected, contamination by bacteria or the like can be prevented without opening / closing the lid of the container or inserting / removing the injection needle.

  Also, when the dispensed amount is out of the desired value, when adjusting the amount by dispensing or suction again, open the lid again or insert / remove the injection needle into the rubber stopper of the container again. Without dispensing, dispensing can be performed while maintaining aseptic conditions.

  Furthermore, by making the pipe connected to the container into a spring pipe having spring properties such as a spring constant in the weight measuring direction, the weight change applied to the container at the time of suction and discharge of liquid to the container is absorbed by the nature of the spring, Measurement accuracy can be improved.

DESCRIPTION OF SYMBOLS 100 ... Mixing part, 101 ... Active ingredient liquid intake port, 102 ... Nitrogen gas intake port, 103 ... Outlet, 104 ... Active drug substance recovery container, 105 ... Diluent liquid container, 106 ... Diluent liquid recovery container, 107 ... Syringe pump, 108 ... Waste liquid collection container, 109 ... synthesis container, 110 ... waste liquid collection container, 111 ... three-way stopcock, 112 ... piping, 113 ... weight measurement unit, 114 ... radiation detector, 115 ... rubber plug, 116 ... injection needle, 117 ... connection part , 118 ... Vent filter, 119 ... Fixed part, 120 ... Spring piping, 121 ... Weight measuring instrument, 122 ... Plate, 123 ... Pillar, 124 ... Holder, 125 ... Lead shield, 126 ... Through hole, 127 ... Lead shield, 128 ... Column, 129 ... Weight measuring sensor, 150 ... Syringe, 151 ... Syringe, 152 ... Container, 153 ... Joint, 154 ... Holder, 200 ... Dispensing part 201 ... individual container, 202 ... filter, 300 ... controller, 400 ... liquid supply portion

Claims (10)

A pipe capable of connecting the first container, the second container, and the third container is provided, and the first liquid in the first container and the second container are connected via the pipe. A mixing part for mixing the second liquid in the third container and adjusting the third liquid;
A dispensing unit for dispensing the third liquid from the third container into a plurality of containers;
A control unit that controls the mixing unit and the dispensing unit;
The mixing unit includes:
A weighing unit that measures the weight of the liquid in at least one of the first container, the second container, and the third container with the container connected to the pipe;
A liquid dispensing system characterized by that. The liquid dispensing system according to claim 1,
The mixing unit includes:
As the pipe connected to the container to be weighed, a spring pipe having a spring property in the measuring part direction is provided.
A liquid dispensing system characterized by that. The liquid dispensing system according to claim 2,
The mixing unit includes:
As the spring pipe, a coiled pipe is provided.
A liquid dispensing system characterized by that. The liquid dispensing system according to claim 2,
The mixing unit includes:
As the spring piping, provided with a spring piping in which a spring constant in the direction of the measuring portion is measured in advance.
A liquid dispensing system characterized by that. The liquid dispensing system according to claim 1,
The weighing unit is
The weighing is performed in a state where the first container, the second container, the third container, and the pipe are sterilized and sealed,
A liquid dispensing system characterized by that. Piping capable of connecting the first container, the second container, and the third container;
A mixing section for mixing the first liquid in the first container and the second liquid in the second container into the third container via the pipe;
A weighing unit that measures the weight of the liquid in at least one of the first container, the second container, and the third container with the container connected to the pipe;
A liquid regulating device characterized by the above. The liquid regulating device according to claim 6,
As the pipe connected to the container to be weighed, a spring pipe having a spring property in the measuring part direction is provided.
A liquid regulating device characterized by the above. The liquid regulating device according to claim 7,
As the spring pipe, a coiled pipe is provided.
A liquid regulating device characterized by the above. The liquid regulating device according to claim 7,
As the spring piping, provided with a spring piping in which a spring constant in the direction of the measuring portion is measured in advance.
A liquid regulating device characterized by the above. The liquid regulating device according to claim 6,
The weighing unit is
The weighing is performed in a state where the first container, the second container, the third container, and the pipe are sterilized and sealed,
A liquid regulating device characterized by the above.

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