JP6348851B2 - Aseptic reagent dispensing kit, dispensing system, and preparation system - Google Patents

Description

  The present invention relates to a sterile reagent dispensing kit, a dispensing system, and a preparation system.

In recent years, the importance of PET (Positron emission tomography) diagnosis that contributes to diagnosis at the molecular level in the field of cancer diagnosis has increased. In PET diagnosis, a radiolabeled drug is used as a tracer. In addition to ¹⁸ F-FDG, which is currently most widely used, various disease-specific radioactive reagents have been actively developed in recent years. The situation is now being applied clinically. That is, in the near future, in order to make a diagnosis according to each disease and each patient, it is expected that a small amount and variety of radioactive reagents will progress.

On the other hand, when such a small amount and a large variety of products have progressed, a single type of drug is mass-produced at several factories as in the current ¹⁸ F-FDG and delivered to medical / inspection institutions. Such an intensive radioactive reagent manufacturing form is expected to be difficult to cope from the viewpoint of an increase in manufacturing cost. Therefore, in the future, we will deliver radioactive substances for labeling such as ¹⁸ F to each clinical site from a centralized type that prepares a large amount of radiodiagnostic drugs at several bases, and a small amount of radioactive reagent will be individually supplied to each clinical site. Dispersed radioactive reagent manufacturing forms to be manufactured and prepared are expected to become mainstream.

  In order to carry out the preparation of radioactive reagents at each clinical site with the increasing number of radioactive reagents, the dispensing operation and the preparation of drugs should be performed in highly aseptic operating areas in order to meet clinical use standards. Is essential. In addition, since the radioactive amount of the radioactive reagent handled at the time of preparation is relatively high, it is important to shorten the work time as much as possible and to reduce the exposure of workers, such as automation of the dispensing process. It becomes.

  So far, there is Patent Document 1 as a technique related to aseptic dispensing of medicines. In Patent Document 1, “the supply fluid flow path from a collection vial (also referred to as a product dispensing vial), a filter, and an associated tube connecting each dispensing vial, the environment between the filter and the inside of the dispensing vial. Is described as “environmentally controlled, preferably sterile, more preferably GMP compliant dispensing system”. Thus, a method is disclosed in which aseptic dispensing can be easily performed on a dispensing vial connected to a sterile filtration filter.

Special table 2011-525142 gazette

  However, in Patent Document 1, a kit used when dispensing a drug into a dispensing vial is composed of a sterile filtration filter and a dispensing vial connected by a fluid flow path whose internal environment is controlled in a sterile state. ing. Using this kit, introduction and dispensing of a drug solution filtered through a sterile filtration filter into a dispensing vial in a sterile state is achieved. However, depending on the properties and characteristics of the drug to be sterile filtered, there is a new problem that the drug solution concentration after filtration is reduced by the adsorption of the drug to the sterile filtration filter compared to the drug concentration before filtration of the sterile filtration filter. . Therefore, even when performing aseptic filtration filter processing, a method is required that enables drug dispensing while maintaining a desired concentration.

  The object of the present invention is to provide a desired radioactivity concentration even in the case where the radioactivity concentration (or drug concentration) of the radioactive reagent in the filtrate is reduced due to the adsorption of the drug to the sterile filtration filter in the aseptic dispensing step of the radioreagent. It is an object of the present invention to provide a sterile reagent dispensing kit and a dispensing system that can achieve the radioactive reagent dispensing.

  In order to solve the above problems, the present application includes a plurality of means for solving the above problems. To give an example, the solution in which the radioactive reagent is dissolved is aseptically filtered, and the filtrate is subjected to a desired concentration of the radioactive reagent. A single-use radioactive reagent dispensing kit for aseptically dispensing with a sterile filtration filter having a liquid reagent introduction section and a sterile outlet at the filtrate outlet of the sterile filtration filter. Disposable containers connected in a state in which a sterile environment is maintained via a connected dispensing channel and a mechanism capable of switching the channel between the dispensing channel, and another dispensing channel. One or more reagent dispensing containers connected in a state where a sterile environment is maintained through a mechanism capable of switching the flow path are provided.

  Another aspect of the present invention is to use a single-use radioactive reagent dispensing kit for aseptically filtering a liquid reagent in which a radioactive reagent is dissolved and aseptically dispensing the filtrate at a desired radioactive reagent concentration. This is a reagent dispensing system. In this system, the radioactive reagent dispensing kit includes a sterile filtration filter having a liquid reagent introduction section, a dispensing channel connected to the filtrate outlet of the sterile filtration filter in a state in which a sterile environment is maintained, and a dispensing flow path. A waste container connected in a state where a sterile environment is maintained via a first flow path switchable mechanism to the injection flow path, and a second flow path switchable mechanism to the dispensing flow path And one or more reagent dispensing containers connected in a sterile environment. Dispose of the radioactive liquid reagent that has fallen below the desired allowable concentration after passing through the sterile filtration filter into the disposal container, and then dispense the sterile filtered radioactive liquid reagent that has reached the desired allowable concentration into the reagent dispensing container. To do. In addition, a sterile radioactive reagent preparation system is incorporated in this radioactive reagent dispensing system by introducing a liquid reagent raw material in which the radioactive reagent is dissolved and diluting the liquid reagent raw material to a desired concentration to produce a liquid reagent. Can also be configured.

  In a preferred configuration example of the present invention, in the above-described system, the filtrate with the concentration of the radioactive reagent being equal to or lower than the desired allowable drug concentration due to adsorption of the radioactive reagent in the liquid reagent to the sterile filtration filter is sent to the waste container. Then, the adsorption of the drug to the sterile filtration filter is stopped due to the saturation of the adsorption of the radioactive reagent to the sterile filtration filter, and the concentration of the radioactive reagent in the filtrate is within the desired allowable drug concentration range. In such a case, the dispensing flow path is switched to dispense the filtrate into the reagent dispensing container.

  Another aspect of the present invention is a single-use radioactive reagent dispensing kit for aseptically filtering a liquid reagent in which a radioactive reagent is dissolved and aseptically dispensing the filtrate at a desired radioactive reagent concentration. This kit includes a sterile filtration filter having a liquid introduction part for a liquid reagent, a dispensing channel connected to the filtrate outlet of the sterile filtration filter while maintaining a sterile environment, and a dispensing channel. A waste container that is connected in a state in which a sterile environment is maintained through a mechanism capable of switching the first flow path, and for discarding a radioactive liquid reagent that has fallen below a desired allowable concentration after passing through a sterile filtration filter; The radioactive liquid reagent having a desired allowable concentration after passing through the sterile filtration filter is connected to the dispensing flow path through a mechanism capable of switching the second flow path and maintaining a sterile environment. One or more reagent dispensing containers are provided for dispensing.

  A preferred specific example of this kit will be described. In this kit, it is desirable to reliably and easily distinguish waste containers from other containers. For this reason, in order to identify a waste container and a reagent dispensing container visually or by touch, an identification unit for displaying that the waste container is a waste container is provided. Alternatively, in order to distinguish the waste container from the reagent dispensing container by visual or tactile sense, the shape of the waste container is made different from that of the reagent dispensing container. Alternatively, the desorption structure of the waste container and the sterile liquid feeding flow path is different from that of other containers. For example, the waste container is structured so that it cannot be easily detached from the sterile liquid supply flow path by locking or adhering. Or you may comprise so that a warning sound or a warning display may be performed when removing a waste container.

  According to the present invention, in the sterile dispensing step at the time of preparation of the radioactive reagent, the sterile filtered radioactive liquid reagent having a concentration below the desired radioactivity concentration can be obtained even when the concentration decreases due to the adsorption of the radioactive reagent to the sterile filtration filter. A sterile reagent dispensing kit that enables dispensing of a desired concentration of radioactive liquid reagent to a reagent dispensing container and a system using the same can be provided by first sending the liquid to a disposal container and discarding it.

  Further features related to the present invention will become apparent from the description of the present specification and the accompanying drawings. Further, problems, configurations and effects other than those described above will be clarified by the description of the following examples.

It is the schematic diagram which showed the structure of the aseptic reagent dispensing kit of the radioactive liquid reagent which concerns on one Embodiment of this invention. It is the schematic diagram which showed the structure of the aseptic reagent dispensing kit of the radioactive liquid reagent which concerns on one Embodiment of this invention. It is the schematic diagram which showed the dispensing method to the disposal container and reagent dispensing container of the radioactive liquid reagent which concerns on one Embodiment of this invention, and flow-path switching timing. It is the schematic diagram which showed the dispensing method to the disposal container and reagent dispensing container of the radioactive liquid reagent which concerns on one Embodiment of this invention, and flow-path switching timing. It is the schematic diagram which showed the dispensing method to the disposal container and reagent dispensing container of the radioactive liquid reagent which concerns on one Embodiment of this invention, and flow-path switching timing. It is the schematic diagram which showed the dispensing method to the disposal container and reagent dispensing container of the radioactive liquid reagent which concerns on one Embodiment of this invention, and flow-path switching timing. It is the schematic diagram which showed the detail of the dispensing method to the disposal container and reagent dispensing container of the radioactive liquid reagent which concerns on one Embodiment of this invention, and flow-path switching timing. It is the schematic diagram which showed the detail of the dispensing method to the disposal container and reagent dispensing container of the radioactive liquid reagent which concerns on one Embodiment of this invention, and flow-path switching timing. It is the schematic diagram which showed the detail of the dispensing method to the disposal container and reagent dispensing container of the radioactive liquid reagent which concerns on one Embodiment of this invention, and flow-path switching timing. It is the schematic diagram which showed the detail of the dispensing method to the disposal container and reagent dispensing container of the radioactive liquid reagent which concerns on one Embodiment of this invention, and flow-path switching timing. It is the graph which showed calculation of the liquid feeding amount at the time of discarding the radioactive liquid reagent which became below the desired radioactivity concentration which concerns on one Embodiment of this invention. It is the schematic diagram which showed the flow-path switching control at the time of discarding the radioactive liquid reagent which became below the desired radioactivity concentration which concerns on one Embodiment of this invention. It is the flowchart which showed the flowchart regarding the method of determining flow-path switching control with the measured value by the radiation detector which concerns on one Embodiment of this invention. It is the graph which showed the relationship between the liquid feed speed which concerns on one Embodiment of this invention, and the filter passage flow volume required for adsorption saturation of the radioactive liquid reagent to a sterile filtration filter. It is the schematic diagram which showed the waste container which comprised the identification part which concerns on one Embodiment of this invention. It is the schematic diagram which showed the waste container which has a shape different from the reagent dispensing container which concerns on one Embodiment of this invention. It is the schematic diagram which showed the waste container which equipped with one embodiment of this invention with the detachment | desorption prevention mechanism from a dispensing needle and a dispensing flow path. It is the schematic diagram which showed storing of the waste container to the waste container storage part which concerns on one Embodiment of this invention. It is the schematic diagram which showed storing of the waste container to the waste container storage part which concerns on one Embodiment of this invention. It is the schematic diagram which showed typically adsorption | suction reduction of the radioactive liquid reagent by adsorption | suction of the blocking chemical | medical agent to the aseptic filtration filter which concerns on one Embodiment of this invention. It is a block diagram which shows an example of the preparation line of the radioactive reagent in a clinical site based on one Embodiment of this invention.

  Embodiments of the present invention will be described below with reference to the accompanying drawings. The accompanying drawings show specific embodiments in accordance with the principle of the present invention, but these are for the understanding of the present invention, and are never used to interpret the present invention in a limited manner. is not. In each drawing, the same reference numerals are assigned to common components.

  In the present specification and the like, notations such as “first”, “second”, and “third” are attached to identify the components, and do not necessarily limit the number or order. In addition, a number for identifying a component is used for each context, and a number used in one context does not necessarily indicate the same configuration in another context. Further, it does not preclude that a component identified by a certain number also functions as a component identified by another number.

  The position, size, shape, range, and the like of each component illustrated in the drawings and the like may not represent the actual position, size, shape, range, or the like in order to facilitate understanding of the invention. For this reason, the present invention is not necessarily limited to the position, size, shape, range, and the like disclosed in the drawings and the like.

  FIG. 1A is an example of an explanatory diagram showing a configuration of a sterile reagent dispensing kit of this example. The sterile reagent dispensing kit of this example can aseptically dispense a liquid reagent with a desired radioactivity concentration into a reagent dispensing container by removing and discarding the radioactive liquid reagent that has fallen below the desired radioactivity concentration. A possible single use kit. The aseptic reagent dispensing kit includes, as main components, a sterile (sterile) filtration filter having a waste container 1, reagent dispensing containers 101 and 102, a sample inlet 3 and a filtrate outlet 4 (which is more biological than a normal environment). (Hereinafter simply referred to as an aseptic filter or filter) 5, a dispensing needle 11 that communicates with the waste container 1, and a dispensing needle 12 that communicates with each of the reagent dispensing containers 101 and 102. , 13, reagent dispensing channels 2a, 2b, 2c and 21, 22, 23, channel switching mechanisms (three-way stopcocks) 31, 32, 33, and vent needles 41, 42, 43 with sterile filters.

  The structure of the sterile reagent dispensing kit will be described in detail below. The sterile reagent dispensing kit is a sample flow for receiving a radioactive liquid reagent prepared in advance in a preparation unit (not shown) to a desired radioactivity concentration via a liquid feeding channel 200 by a liquid feeding unit (not shown). Filtrate in which the concentration of the radioactive reagent in the filtrate is less than the desired concentration due to adsorption of the sterile reagent 5 having the inlet 3 and the filtrate outlet 4 for discharging the filtrate, and the radioactive reagent at the time of filter filtration. A waste container 1 for removing and discarding the reagent from the reagent dispensing flow path, a reagent dispensing container 101, 102 for dispensing the filtrate having a desired concentration, a waste container 1, and a reagent dispensing container 101, Dispensing needles 11, 12, 13 communicating with 102, reagent dispensing channels 2a, 2b, 2c and 21, 22, 23 communicating with these dispensing needles, and a channel switching mechanism (three-way stopcock) ) Consists of 31, 32, 33 It is. In addition, the radioactive liquid of the reagent dispensing flow paths 2a, 2b, 2c, 21, 22, 23, flow path switching mechanisms 31, 32, 33, the waste container 1, and the reagent dispensing containers 101, 102 after the filtrate outlet 4 All reagent contact surfaces remain sterile.

  FIG. 1B is a schematic diagram illustrating a modification of the present embodiment. Although FIG. 1A shows the case where there are two reagent dispensing containers 101 and 102, the number is not particularly limited to two and may be any number. As another embodiment shown in FIG. 1B, a reagent dispensing flow path branches at the flow separation switching mechanism 36, and a configuration of an aseptic dispensing kit capable of dispensing into four reagent dispensing containers 101, 102, 103, 104 is provided. Show.

  2A to 2D show an embodiment relating to a method for dispensing radioactive liquid reagent into a waste container and a reagent dispensing container, and flow path switching timing.

  As shown in FIG. 2A, the control unit 501 that controls the liquid feeding and flow path switching mechanism controls the flow path switching mechanism 31, and causes the reagent dispensing flow path 2a, the flow path 21, and the dispensing needle 11 to communicate with each other. Thereafter, the liquid feeding part (not shown) is operated to pass the radioactive liquid reagent into the sample inlet through the reagent dispensing channel 200 connected to the reagent preparing part (not shown) for preparing the radioactive liquid reagent to a desired radioactivity concentration. 3 to aseptic filter 5 and aseptic filtration is performed. During filtration with the aseptic filter 5, the concentration of the radioactive reagent in the filter filtrate decreases due to the adsorption of the radioactive reagent to the filter. Therefore, the filtration passes through the filtrate outlet 4 and the reagent dispensing channel 2a at the beginning of filtration. The concentration of the radioactive reagent in the liquid is lower than the desired radioactive concentration of the radioactive liquid reagent introduced into the sample inlet 3. As shown in FIG. 2B, the filtered radioactive reagent solution having a concentration lower than the desired radioactivity concentration is discarded from the filtrate outlet 4 of the sterile filter 5 through the reagent dispensing flow path 2a, the flow path switching mechanism 31, and the flow path 21. Dispense into container 1 and discard. Next, the adsorption of the radioactive reagent to the filter reaches saturation, the concentration of the radioactive reagent in the filtrate reaches the desired radioactivity concentration, and the filtrate tip that has the desired radioactivity concentration passes through the flow path switching mechanism 31 and passes through the flow path. As shown in FIG. 2C, the control unit 501 controls the flow path switching mechanism 31 to introduce a reagent dispensing flow path 21 that holds a radioactive reagent having a desired radioactivity concentration or less, as shown in FIG. The connection of the needle 11 and the waste container 1 to the reagent dispensing channel 2a is blocked. As a result, the filtered radioactive liquid reagent having a concentration below the desired radioactivity concentration can be excluded from the liquid supply channels 2a, 2b, and 2c for dispensing the reagent into the reagent dispensing containers 101 and 102. Next, as shown in FIG. 2D, the control unit 501 controls the flow path switching mechanism 32 to cause the reagent dispensing flow paths 2a, 2b, 22, the dispensing needle 12 and the reagent dispensing container 101 to communicate with each other. The liquid part (illustration omitted) is operated, the radioactive liquid reagent after filtration of desired radioactivity density | concentration is introduce | transduced into the reagent dispensing container 101, and it dispenses. After the desired amount of filtered radioactive liquid reagent has been dispensed into the reagent dispensing container 101, the desired amount is dispensed into the reagent dispensing container 102 after the flow path switching mechanisms 32 and 33 are switched.

  FIG. 3A to FIG. 3D are explanatory views showing details of a method for dispensing radioactive liquid reagent into a waste container and a reagent dispensing container and flow path switching timing as an example. 3A to 3D correspond to FIGS. 2A to 2D, respectively.

  FIG. 3A shows the state of the cock cock 311 when the flow path switching mechanism 31 is switched by the control unit and the reagent dispensing flow paths 2 a and 21 are communicated with each other via the flow path switching mechanism 31. A radioactive reagent solution portion 111 having a desired radioactivity concentration obtained by introducing the radioactive liquid reagent from the sample inlet 3 to the aseptic filter 5 through the reagent dispensing channel 200 by the liquid feeding unit (not shown) is supplied to the aseptic filter 5. Due to the adsorption of the radioactive reagent, the radioactive reagent solution portion 112 having a concentration below the desired radioactivity concentration is introduced from the filtrate outlet 4 at the beginning of filtration into the reagent dispensing flow path 2a.

  Further, the liquid feeding is continued, and the radioactive reagent solution portion 112 having a desired radioactivity concentration or less is discarded in the dispensing needle 11 and the disposal container 1 (not shown) communicating with the reagent dispensing channel 21.

  Next, the adsorption of the radioactive reagent to the sterile filter is saturated, and the radioactive reagent solution portion 111 in which the concentration of the radioactive reagent after filtration by the sterile filter is a desired radioactive concentration and the radioactive reagent solution portion 112 that is equal to or less than the desired radioactive concentration. FIG. 3C shows a state in which the flow path switching mechanism 31 is switched by the control section when the boundary area 312 is discharged from the flow path section of the stopcock cock 311. At this time, since the radioactive reagent solution portion 112 having a concentration below the desired radioactivity concentration is isolated from the reagent dispensing channels 2a and 2b communicating with the reagent dispensing container, it is not dispensed into the reagent dispensing container. Absent. The liquid delivery is started from the state of FIG. 3C, and as shown in FIG. 3D, the radioactivity having a desired radioactivity concentration is obtained in the reagent dispensing container (not shown) communicating with the reagent dispensing channel 2b. Delivery and dispensing of the reagent solution portion 112 is accomplished.

  With reference to FIG. 4, an embodiment relating to the calculation of the liquid feeding amount when discarding a radioactive liquid reagent having a desired radioactivity concentration or less will be described.

  In the preparation and dispensing of the radioactive liquid reagent, the desired radioactivity concentration of the radioactive liquid reagent is generally set as an acceptable drug concentration range. Therefore, the reagent dispensing container may be dispensed with the desired radioactivity concentration when the drug concentration or radioactivity amount in the filtrate after passing through the sterile filter is within the allowable drug concentration range or radioactivity amount range.

  As shown in FIG. 4, in a region where the flow rate through the filter is small, the drug concentration or radioactivity amount in the filtrate falls below the allowable drug concentration region or radioactivity amount region due to adsorption of the radioactive reagent to the sterile filter. As the flow rate through the filter increases, the adsorption of the radioactive reagent to the sterile filter decreases, and when the amount of radioactive liquid reagent passing through the filter reaches P, the concentration of drug in the filtrate or the amount of radioactivity is within the allowable drug concentration range or radiation. Reach the capacity range. After the filter passage amount reaches P, the adsorption to the filter is saturated, and the radioactivity concentration in the filtrate becomes an allowable drug concentration range, that is, a desired radioactivity concentration.

  Accordingly, the filtrate that has passed through the filter up to the filter passage amount P can be discarded, and the filtrate that passes through the filter after the passage amount P can be dispensed into the reagent dispensing container. May be the time when the amount of liquid that is the filter passage amount P is fed.

  Since the value that becomes the filter passage amount P varies depending on the size and pore diameter of the filter used for aseptic filtration and the radioactive amount of the radioactive liquid reagent, the filter passage amount P may be calculated in advance through experiments or the like. As a value to be directly controlled at the time of the dispensing process, it is only necessary to monitor the amount of liquid passing through the filter as described above and control the flow path switching at the timing of the predetermined amount of liquid passing through. Alternatively, if the conditions of the filter, the medicine, etc. are fixed, calculate the time required for a predetermined amount of fluid to pass and control the flow path switching by the time until the amount of fluid passes. May be. Alternatively, the channel switching may be controlled by directly measuring the radioactivity concentration in the solution.

  FIG. 5 illustrates an embodiment relating to the flow path switching timing when the radioactive liquid reagent having a concentration below the desired radioactivity concentration is discarded.

  FIG. 5 shows a state in which radiation detectors 201 and 202 are installed in the vicinity of the dispensing channel 200 and the reagent dispensing channel 2a through which the radioactive liquid reagent is fed in the aseptic filtration process. Thereby, it is possible to measure the radioactivity concentration of the radioactive liquid reagent before and after filtration by the aseptic filter 5 by the radiation detectors 201 and 202.

  The measured radioactivity concentration by the radiation detector 201 is the same value as the desired radioactivity concentration set by the preparation unit (not shown). On the other hand, the radioactivity concentration measurement value by the radiation detector 202 becomes lower than the radioactivity concentration measurement value by the radiation detector 201 due to the adsorption of the radioactive reagent to the sterile filter 5. As the flow rate through the filter increases, the adsorption of the radioactive reagent to the aseptic filter 5 decreases. As a result, the measured radioactivity concentration by the radiation detector 202 becomes asymptotic to the measured radioactivity concentration by the radiation detector 201. Eventually, the same measured value is obtained due to the saturation of the adsorption of the radioactive reagent to the sterile filter 5.

  As a result, when the difference between the measurement values obtained by the radiation detectors 201 and 202 is greater than or equal to the allowable range of the reagent concentration during aseptic filtration, the flow path switching mechanism 31 is configured to discharge the filter filtrate to the waste container 1. And the radioactive liquid reagent having a desired radioactivity concentration or less may be discarded. When the difference between the measurement values obtained by the radiation detectors 201 and 202 is less than or equal to the allowable range of the reagent concentration, the flow path switching mechanism 31 is switched, and the flow paths 2a and 2b are connected to each other. By dispensing the solution into a radioactive liquid reagent having a desired radioactivity concentration can be achieved.

  Details of the method for determining the flow path switching timing based on the measurement values obtained by the radiation detector of FIG. 5 will be described using the flowchart shown in FIG.

  First, the control unit (not shown) operates the flow path switching mechanism 31 to connect the flow path to the disposal container (1001). Next, the liquid supply unit (not shown) is driven to start liquid supply, and the radioactive liquid reagent is introduced into the sterile filter and filtered (1002). The amount of radioactivity of the solution passing through the channel installed in the vicinity is measured by the radiation detector (1003). A control unit (not shown) including the measurement result receiving unit and the analysis unit receives the measurement result (1004), and calculates the difference between the measurement values of the radiation detectors 201 and 202. When this difference value exceeds the allowable range value of the radioactivity concentration, liquid feeding is continued and the filtrate is introduced into the waste container 1. Next, when the difference value is within the allowable range of the radioactivity concentration, it is determined that the filtrate has reached the desired radioactivity concentration (1005), and the flow path switching mechanism 31 is switched by an instruction from the control unit. (1006) By connecting the liquid supply flow path to the reagent dispensing container, dispensing to the reagent dispensing container is performed (1007), and the process ends. This control is performed every time a reagent dispensing kit is newly replaced and installed, and an aseptic filtration dispensing operation is performed.

  FIG. 7 shows an embodiment relating to the reduction of the flow rate through the filter required for the adsorption saturation of the radioactive liquid reagent on the sterile filter by controlling the liquid feeding speed.

  FIG. 7 schematically shows the relationship between the amount of liquid passing through a sterile filter at different liquid feeding speeds (high speed and low speed) and the radioactive concentration of the radioactive liquid reagent in the filtrate. As shown in FIG. 7, the adsorption amount of the radioactive reagent to the aseptic filter increases as the liquid feeding speed decreases. As a result, the amount of liquid passing through the filter until the adsorption saturation is reached is a smaller value (Ps) than Pf when the liquid feeding speed is high. In the present invention, the solution is switched from disposal to dispensing at the time of filter adsorption saturation, but the fact that the amount of liquid passing through the filter until this adsorption saturation is small means that the amount of liquid discarded can be reduced. ing. In general, the radioactive liquid reagent that is the subject of the present invention is often expensive, and the amount of waste liquid at the time of sterile filtration dispensing can be reduced by reducing the liquid feeding speed as in this embodiment. Is also important in terms of cost reduction. In FIG. 7, the liquid feeding speed is constant at high speed and low speed, but it may be configured such that the liquid is fed at low speed until the filter adsorption saturation and then fed at high speed. In this way, the amount of waste liquid can be reduced and the dispensing processing time can be shortened.

  8 to 11 show an embodiment relating to prevention of misuse of a radioactive liquid reagent having a desired radioactivity concentration or less dispensed in a waste container.

  In the present invention, the radioactive liquid reagent dispensed into the reagent dispensing containers 101 and 102 at a desired radioactivity concentration is withdrawn from the dispensing needles 12 and 13 after dispensing, and administered to the subject. Used for. At this time, it is necessary to prevent the filtered radioactive liquid reagent in the disposal container 1 that has been discarded because the concentration is below the desired radioactivity concentration from being accidentally administered to the subject. Therefore, a means for preventing erroneous use of the filtered radioactive liquid reagent in the waste container 1 is required.

  In FIG. 8, the waste container equipped with the identification part 301 for clearly showing that it is a waste container on the surface of the waste container 1 is shown. This prevents the user from using the radioactive liquid reagent in the waste container 1 by mistake. As for the identification unit 301, any display may be used as long as the display content and shape (size, color, fluorescence, etc.) can be clearly identified from the reagent dispensing containers 101 and 102.

  FIG. 9 shows a case where the disposal container has a shape different from that of the reagent dispensing containers 101 and 102. The shape of the reagent dispensing container 302 may be any shape as long as the reagent dispensing containers 101 and 102 are clearly distinguished. Further, by using a material different from the reagent dispensing container, it may be possible to distinguish it from the reagent dispensing container.

  FIG. 10 illustrates one embodiment for preventing misuse in another form. In FIG. 10, the waste container 1 having a mechanism 303 for preventing detachment from the dispensing needle 11 and the dispensing flow path 21 is shown. The reagent dispensing container is used for subject administration after being removed from the dispensing needle and the flow path, but by providing a mechanism in which the disposal container cannot be detached, the radioactive liquid reagent having a concentration equal to or lower than the desired concentration in the disposal container is provided to the subject. It is possible to prevent misuse.

  11A and 11B show an embodiment relating to misuse prevention in yet another form. FIG. 11A shows a configuration in which the sterile reagent dispensing system of the present invention includes the storage unit 400 of the disposal container 1. In the present embodiment, after completion of the dispensing operation of the radioactive liquid reagent, before the step of pulling out the reagent dispensing containers 101 and 102 from the dispensing needles 12 and 13, a waste container removing mechanism (not shown) installed in the system is used. The disposal container 1 holding the radioactive liquid reagent of a desired concentration or less is removed from the dispensing needle 11 and the dispensing channel 21, and the disposal container 1 is stored in advance in the disposal container storage unit 400 as shown in FIG. 11B. Thus, when the reagent dispensing container is subsequently removed, it is impossible for the operator to use the disposal container 1, and it is possible to prevent the radioactive liquid reagent having a desired concentration or less in the disposal container from being misused.

  FIG. 12 shows an embodiment relating to the reduction of the adsorption of the radioactive liquid reagent by the adsorption of the blocking drug (precursor, unlabeled drug, etc.) to the aseptic filter 5.

  In the adsorption saturation of FIG. 12, the radioactive reagent 901 is adsorbed to the aseptic filter 5, and the solution that passes through the filter after the adsorption is saturated has no decrease in drug concentration and may be transferred to the reagent dispensing container. . FIG. 12 shows a blocking reagent 902 that adsorbs to a filter and reduces the adsorption of the radioactive reagent 901 to the filter. The radioactive reagent 901 is saturated with the filter by passing through the filter before the radioactive reagent 901 is filtered, and then filtered. A method of preventing the adsorption of the filter 901 is shown. This not only achieves dispensing of the radioactive reagent at the desired radioactivity concentration by filter adsorption, but also reduces the amount of radioactive reagent that will be lost by filter adsorption.

  FIG. 13 is an example of a radioactive reagent preparation line at a clinical site. It consists of a cyclotron 1301, a reagent synthesizer 1302, a dilution device 1303, and a dispensing device 1304. The cyclotron 1301 produces radioactive atoms (positron nuclide). In the reagent synthesizer 1302, the produced positron nuclide is labeled on the precursor compound that is the source of the drug by various methods to prepare the target drug. And after diluting and preparing to a desired density | concentration with the dilution apparatus 1303, the radiopharmaceutical for 1 time is dispensed with the dispensing apparatus 1304.

  The dispensing apparatus 1304 includes a control system 1305 including an electronic circuit, a mechanical system 1306 that operates mechanically under the control of the control system, measuring instruments (not shown), and the dispensing unit 1307 described with reference to FIGS. . The control system 1305 includes a configuration for processing the measurement values obtained by the above-described control unit 501 and the measuring instruments. The mechanical system 1306 includes a configuration that mechanically drives the above-described flow path switching mechanisms (three-way cocks) 31, 32, 33, 34, 35, a waste container removal mechanism (see FIG. 11), and the like. The measuring instruments include the radiation detectors 201 and 202 described above.

  From the above, according to the present invention, in the sterile dispensing step at the time of preparation of the radioactive reagent, even when the radioactive concentration of the radioactive reagent is reduced due to adsorption of the radioactive reagent to the sterile filter, the radioactivity of the desired radioactive concentration is obtained. An aseptic reagent dispensing kit and a dispensing system that enable reagent dispensing can be provided. More specifically, a sterile filter for aseptically filtering the radioactive liquid reagent, a dispensing channel connected to the filtrate outlet of the sterile filter while maintaining a sterile environment, and a flow between the dispensing channel and the dispensing channel. A waste container connected in a state in which a sterile environment is maintained through a path-switchable mechanism, and further connected to a dispensing flow path in a state in which a sterile environment is maintained through another channel-switchable mechanism By using a sterile reagent dispensing kit equipped with one or more reagent dispensing containers, the sterile filtered radiopharmaceutical liquid reagent having a concentration below the desired radioactivity concentration is first sent to a disposal container and discarded. The sterile filtered radiopharmaceutical liquid reagent having a desired radioactivity concentration can be aseptically dispensed into the reagent dispensing container.

  The present invention is not limited to the above-described embodiments, and includes various modifications. The above embodiments have been described in detail for easy understanding of the present invention, and are not necessarily limited to those having all the configurations described. Also, a part of the configuration of one embodiment can be replaced with the configuration of another embodiment. Moreover, the structure of another Example can also be added to the structure of a certain Example. Further, with respect to a part of the configuration of each embodiment, another configuration can be added, deleted, or replaced.

DESCRIPTION OF SYMBOLS 1 ... Waste container, 2a, 2b, 2c, 2d, 2e, 21, 22, 23, 24, 25 ... Reagent dispensing flow path, 3 ... Sample inlet, 4 ... Filtrate outlet, 5 ... Aseptic filter, 11 12, 13, 14, 15 ... dispensing needle, 31, 32, 33, 34, 35 ... flow path switching mechanism (three-way stopcock), 41, 42, 43, 44, 45 ... vent needle with sterile filter, 101, 102, 103, 104 ... Reagent dispensing container, 111 ... Radioactive reagent solution portion with desired radioactivity concentration, 112 ... Radioactive reagent solution portion with lower than desired radioactivity concentration, 201, 202 ... Radiation detector, 311 ... Stopcock cock , 312 ... boundary area, 400 ... waste container storage unit, 501 ... control unit, 901 ... radioactive reagent, 902 ... blocking agent, 1301 ... cyclotron, 1302 ... reagent synthesizer, 1303 ... dilution apparatus, 130 ... dispenser, 1305 ... control system consisting of an electronic circuit, 1306 ... control system mechanically operated to mechanical system under the control of, 1307 ... dispensing unit

Claims (15)

A reagent dispensing system using a single-use radioactive reagent dispensing kit for aseptically filtering a liquid reagent in which a radioactive reagent is dissolved and aseptically dispensing the filtrate at a desired radioactive reagent concentration,
The radioactive reagent dispensing kit is
A sterile filtration filter having a liquid introduction part for the liquid reagent;
A dispensing channel connected to the filtrate outlet of the sterile filtration filter while maintaining a sterile environment;
A waste container connected to the dispensing flow path in a state in which a sterile environment is maintained via a first flow path switchable mechanism;
Comprising one or more reagent dispensing containers connected to the dispensing channel in a state where a sterile environment is maintained via a second channel switching mechanism;
After passing through the sterile filtration filter, the radioactive liquid reagent that has fallen below the desired allowable concentration is dispensed and discarded into the waste container, and then the sterile filtered radioactive liquid reagent having the desired allowable concentration is dispensed into the reagent dispensing container. Aseptic reagent dispensing system. In the sterile reagent dispensing system according to claim 1,
Due to the adsorption of the radioactive reagent in the liquid reagent to the sterile filtration filter, the filtrate with the concentration of the radioactive reagent being equal to or lower than a desired allowable drug concentration is sent to the waste container and discarded. When the adsorption of the radioactive reagent to the sterile filtration filter reaches saturation, the adsorption of the radioactive reagent to the sterile filtration filter stops, and the concentration of the radioactive reagent in the filtrate falls within a desired allowable drug concentration range And the dispensing flow path is switched to dispense the filtrate into the reagent dispensing container.   The amount of the liquid reagent liquid reagent that passes through the sterile filtration filter before the saturation of adsorption of the radioactive reagent on the sterile filtration filter for each target reagent to be sterile filtered with the sterile filtration filter in advance and the type of sterile filtration filter to be used 3. The sterile reagent dispensing system according to claim 2, wherein the filtrate is calculated for each of the liquid reagent and the amount of the liquid reagent that is less than or equal to the permissible drug concentration is discharged to the waste container and discarded. . Radiation detectors are installed in the vicinity of the flow path of the liquid reagent introduction part and the filtrate outlet of the sterile filtration filter, respectively, and the radiation measurement value of the radioactive reagent liquid reagent before passing through the sterile filtration filter and the vicinity of the filtrate outlet Measure the radiation measurement value of the filtrate, and when the difference between the measurement values is within the allowable range, operate the flow channel switching mechanism to switch the fluid flow channel to communication with the reagent dispensing container. for example, sterile reagent dispensing system according to claim 2, wherein the dispensing radioactive liquid reagent reaches a desired activity concentration in the reagent dispensing containers.   By setting the liquid feeding speed until the adsorption of the radioactive reagent to the sterile filtration filter is saturated compared to the liquid feeding speed after the adsorption saturation, adsorption saturation is efficiently generated and distributed to the waste container. 4. The sterile reagent dispensing system according to claim 3, wherein the amount of the filtered chemical solution poured and discarded is reduced.   A mistake may be made between the waste container holding the radioactive reagent filtrate below the allowable drug concentration and the reagent dispensing container dispensing and holding the radioactive reagent filtrate within the allowable drug concentration range. The aseptic reagent dispensing system according to claim 2, further comprising an identification unit for indicating that the waste container is a waste container.   A mistake may be made between the waste container holding the radioactive reagent filtrate below the allowable drug concentration and the reagent dispensing container dispensing and holding the radioactive reagent filtrate within the allowable drug concentration range. The sterile reagent dispensing system according to claim 2, wherein the shape of the waste container is different from that of the reagent dispensing container in order to avoid the problem. To prevent the accidental use of the waste container holding the radioactive reagent filtrate below the acceptable drug concentration, to have a mechanism in which the waste container can not be detached from the flow path of the radioactive reagent filtrate The sterile reagent dispensing system according to claim 2, wherein the dispensing system is sterile.   In order to prevent accidental use of the waste container holding the radioactive reagent filtrate having a concentration equal to or lower than the permissible drug concentration, a waste container stored in advance is stored before the user collects the reagent dispensing container. The sterile reagent dispensing system according to claim 2, further comprising a mechanism that transports and stores the waste container to a section so that a user cannot contact the waste container. The is not a radioactive reagent, the sterile to the filtration filter is passed through a buffer containing agents with adsorptivity to advance the sterile filtration filter, by saturating adsorb the drug to the sterile filtration filter, followed by the sterile sterile reagent dispensing system according to claim 2, characterized in that reducing the adsorption to the sterile filtration filter of radioactive reagents contained drug solution of interest to be filtered through a filter filters. A single-use radioactive reagent dispensing kit for aseptically filtering a liquid reagent in which a radioactive reagent is dissolved, and aseptically dispensing the filtrate at a desired radioactive reagent concentration,
A sterile filtration filter having a liquid introduction part for the liquid reagent;
A dispensing channel connected to the filtrate outlet of the sterile filtration filter while maintaining a sterile environment;
A radioactive liquid that is connected to the dispensing flow path through a first flow path switchable mechanism while maintaining a sterile environment, and that has passed through the sterile filtration filter and has reached a desired allowable concentration or less. A waste container for discarding the reagent;
A radioactive liquid reagent that is connected to the dispensing flow path through a second flow path switchable mechanism while maintaining a sterile environment, and has reached a desired allowable concentration after passing through the sterile filtration filter the for dispensing, comprising one or more of the reagent dispensing containers,
Said liquid reagent has become less desired permissible concentration after passing through the sterile filtration filter after dispensing discarded into the waste container, the liquid reagent was the desired permissible concentration in said reagent dispensing container dispensing sterilized Reagent dispensing kit.   The sterile reagent dispensing kit according to claim 11, further comprising an identification unit for displaying that the waste container is a waste container in order to identify the waste container and the reagent dispensing container. .   The sterile reagent dispensing kit according to claim 11, wherein the shape of the waste container is different from that of the reagent dispensing container in order to distinguish the waste container and the reagent dispensing container. The aseptic structure according to claim 11, wherein the desorption structure of the waste container and the flow path of the radioactive reagent filtrate is different from the desorption structure of the flow path of the other container and the radioactive reagent filtrate. Reagent dispensing kit. A dilution unit for introducing a liquid reagent raw material in which a radioactive reagent is dissolved, and diluting the liquid reagent raw material to a desired concentration to generate a liquid reagent;
A sterile reagent preparation system having a dispensing unit for introducing the generated liquid reagent and dispensing the introduced liquid reagent into a predetermined amount,
The dispensing unit uses a single-use radioactive reagent dispensing kit for aseptically filtering the liquid reagent and aseptically dispensing the filtrate at a desired radioactive reagent concentration,
The radioactive reagent dispensing kit is
A sterile filtration filter having a liquid introduction part for the liquid reagent;
A dispensing channel connected to the filtrate outlet of the sterile filtration filter while maintaining a sterile environment;
A waste container connected to the dispensing flow path in a state in which a sterile environment is maintained via a first flow path switchable mechanism;
A reagent dispensing container connected to the dispensing channel in a state in which a sterile environment is maintained via a second channel switching mechanism;
After passing through the sterile filtration filter, the radioactive liquid reagent that has fallen below the desired allowable concentration is dispensed and discarded into the waste container, and then the sterile filtered radioactive liquid reagent having the desired allowable concentration is dispensed into the reagent dispensing container. A sterile reagent preparation system.

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