WO2019228392A1 - 一次性反应装置和一种示踪剂合成仪及其生产示踪剂方法 - Google Patents

一次性反应装置和一种示踪剂合成仪及其生产示踪剂方法 Download PDF

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Publication number
WO2019228392A1
WO2019228392A1 PCT/CN2019/088972 CN2019088972W WO2019228392A1 WO 2019228392 A1 WO2019228392 A1 WO 2019228392A1 CN 2019088972 W CN2019088972 W CN 2019088972W WO 2019228392 A1 WO2019228392 A1 WO 2019228392A1
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Prior art keywords
disposable
needle
reaction
tracer
reactor
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PCT/CN2019/088972
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English (en)
French (fr)
Inventor
张建中
方玉
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杭州启创生物技术有限公司
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Priority to US17/059,452 priority Critical patent/US12005415B2/en
Publication of WO2019228392A1 publication Critical patent/WO2019228392A1/zh

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0053—Details of the reactor
    • B01J19/0073—Sealings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/24—Stationary reactors without moving elements inside
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0006—Controlling or regulating processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0053—Details of the reactor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/52—Containers specially adapted for storing or dispensing a reagent
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G4/00—Radioactive sources
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00002—Chemical plants
    • B01J2219/00004—Scale aspects
    • B01J2219/00011—Laboratory-scale plants
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/044—Connecting closures to device or container pierceable, e.g. films, membranes

Definitions

  • the invention relates to the technical field of instruments, in particular to a disposable reaction device, a tracer synthesizer and a method for producing a tracer.
  • PET-CT Pulsitron Emission Computer Tomography
  • 18F, 11C, 13N and other radionuclides are manufactured by a cyclotron, and then these radionuclides are labeled on different chemical substrates through a chemical synthesis module (also known as a synthesizer) to synthesize various tracers for clinical use.
  • Agent Because the positron radioactive tracer has the characteristics of high radioactivity and short half-life, it is fully synthesized by a chemical synthesizer using trace reagents.
  • 18F-PDG is still the most widely used tracer in clinical use.
  • Time is wasted. It takes more than 24 hours to perform one synthesis.
  • radioactive 18F will be first generated by the accelerator. Even a small amount of demand will require a bombardment, which will cause a low utilization rate and increase costs.
  • the present invention provides a disposable reaction device and a tracer synthesizer and a method for producing the tracer.
  • a disposable reaction device can be removed after use, and there is no cleaning.
  • Problems such as pipelines solve the problems of waiting, cleaning, waste, pollution, etc., and can repeatedly synthesize tracers in a short time, and more in line with the requirements of GMP.
  • the present invention provides a disposable reaction device, including:
  • Disposable reagent bottles used to load the substances required for the reaction, including radioisotopes, solvents, reagents, and reactants; the load can be filled into the disposable reactor directly or through a disposable liquid pipeline; disposable reagent bottles can be Various shapes and materials, as long as they meet the requirements of the loaded materials, after use can generally be easily removed.
  • the disposable reactor is used for containing the radioisotope and at least one reagent for reaction, and can be sealed with a pierceable member.
  • Disposable liquid pipelines include evaporation elements, filling elements, retracting elements, and mass transfer lines; the evaporation elements, filling elements, and retracting elements all include needle a, needle b, and fixing pieces; needle a and needle b are pierced and fixed on In the fixed part; the structure of the evaporation element, the filling element, and the retracting element are the same, but because the purpose and the method of use are different, in order to better understand the present invention, different names are given.
  • the evaporation element is used for drying, evaporating or concentrating the contents in the disposable reactor, injecting nitrogen or other inert gas through the needle a, and exhausting gas and moisture through the needle b.
  • the filling element is used for filling the substance loaded in the disposable reagent bottle into the disposable reactor, filling the material through the needle a, and exhausting the gas through the needle b.
  • the retracting element is used to remove the intermediate or product after the reaction from the disposable reactor.
  • the gas is injected through the needle b to increase the pressure in the disposable reaction bottle, and the content in the disposable reaction bottle is retrieved through the needle a.
  • One end of the mass transfer line can be connected to a disposable reagent bottle, and the other end is connected to the needle a of the disposable liquid pipeline; the other end of the needle a can be directly or pierced into the disposable reactor and extended into the disposable reactor.
  • the fixing member is composed of a sealing member and a ring, and the bottom of the ring is fixedly connected to the sealing member.
  • the needle a is 7-shaped, one end passes through the side wall of the ring, and the other end passes through the seal; the end of the needle b located in the ring is lower than the height of the ring, and the other end of the needle b is shorter than the needle a on the same side .
  • the needle b is shorter in the reaction bottle than the needle a, which is more conducive to exhausting or injecting gas.
  • Disposable reagent bottles, disposable liquid pipes, and disposable reactors can be removed after use.
  • the radioisotope is fluorine-18, and may also be a commonly used radionuclide such as 11C, 13N, and the like.
  • the invention also provides a tracer synthesizer, which comprises the above-mentioned disposable reaction device, a connecting member and a needle c, and one end of the needle c passes through the connecting member.
  • the upper port of the ring is in contact with the bottom of the connecting piece, and the fixing piece is connected to the connecting piece by applying external air pressure. After the air pressure is released, the fixing piece can be separated from the connecting piece.
  • the invention connects the fixing member and the connecting member by external air pressure, instead of connecting by commonly used methods such as riveting, screws, etc., and realizes fully automated production. The connection and separation are very convenient. At the same time, because the production of radioactive tracer is due to radiation The reason is that they are produced in a closed manner.
  • the fixing piece and the connecting piece After the fixing piece and the connecting piece are connected by external air pressure, the fixing piece and the connecting piece form a closed space.
  • the needle c and the needle b have a fault in the middle, they are connected through the closed space to form a complete channel, which can react to The bottle is filled with gas, and it can also be exhausted from the reaction bottle. Because the needle c is not directly connected to the needle b, the needle c and the connector do not contact the reactants, and do not need to be removed after the reaction, which can simplify the steps, Reduce the cost.
  • the invention also provides a method for producing a tracer by the above synthesizer, comprising the following steps:
  • the one-time reaction device enables the same or different tracer synthesis to be repeated in a short time, greatly improving the tracer. Research and production efficiency.
  • Figure 1 shows the process of filling non-disposable filling elements
  • Figure 2 shows the process of taking out the original non-disposably
  • FIG. 4 is a process of taking out an original in one time in the present invention
  • the labels in the picture are: disposable liquid pipe (1), needle a (101), needle b (102), fixing piece (103), seal (1031), ring (1032), disposable reaction bottle (2) , Can pierce the component (201), the connector (3), the needle c (4).
  • Radiotracer synthesis requires radioisotopes and at least one reagent. Radiotracer synthesis may involve one or more reaction steps to produce a radioactive intermediate or radiochemical product, which may be purified as a tracer. Radiotracer synthesizers also involve multiple devices, such as accelerators that generate radionuclides, temperature control elements that provide energy, and mobile devices that install or remove devices.
  • the present invention is a disposable reaction device that involves its synthesis steps, The other steps and other devices involved in the production of the radiotracer are regarded as the prior art possessed by those skilled in the art, and will not be repeated here.
  • the invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided to ensure that this disclosure is thorough and complete, and to ensure that it fully conveys the scope of the invention to those skilled in the art.
  • the filling process of the non-disposable filling element used in the existing tracer synthesizer is: the reaction bottle 2 moves below the liquid pipe 1, the liquid pipe 1 moves downward, and the substance required for the reaction passes through the needle a101 Fill in the reaction bottle 2 and exhaust through the needle b102. After the reaction is completed, the liquid pipe 1 moves upward.
  • the reaction bottle 2 After the reaction is completed, after the evaporation process, the reaction bottle 2 is moved below the other liquid pipes, and the step of taking out the contents of the reaction bottle 2 is prepared. As shown in FIG. 1 moves down, injects gas through the needle b102, and then takes out the contents through the needle 1.
  • the liquid pipeline 1 is composed of a seal 1031 and a needle a101 and a needle b102 passing through the seal 1031.
  • the liquid pipeline 1 has been contaminated by radionuclides and reaction liquid during the reaction. However, it is not a disposable device. If the next reaction is required, the liquid pipeline 1, reaction flask 2 and other equipment need to be cleaned and wait for the radioactive decay of 10 half-lives before the next tracer production.
  • the present invention provides a disposable reaction device, including:
  • Disposable reagent bottles which can be multiple, are loaded with radioactive isotopes, solvents, reagents, and reactants; the contents of the disposable reagent bottles can be filled into the disposable reactor 2 sequentially and gradually through the disposable liquid pipeline 1 .
  • the disposable reactor 2 is configured to contain a radioisotope and at least one reagent for reaction, and may be sealed with a pierceable member 201. Although a seal 1031 is used for sealing during the reaction, after the piercing member 201 is added to seal, the sealed state can be maintained after the liquid pipe 1 is removed, and the influence caused by radionuclide radiation.
  • Disposable liquid pipe 1 includes evaporation element, filling element, retraction element, and mass transfer line; among them, the evaporation element, filling element, and retraction element include needle a101, needle b102, and fixing piece 103; needle a101 and needle b102 are pierced and It is fixed in the fixing piece 103; the evaporation element is used for drying, evaporating or concentrating the content in the disposable reactor, spraying nitrogen or other inert gas through the needle a101, and exhausting gas and moisture through the needle b102.
  • the filling element is used to fill the substance loaded in the disposable reagent bottle into the disposable reactor, fill the material through the needle a101, and exhaust the gas through the needle b102.
  • the retraction element is used to remove the intermediate or product after the reaction from the disposable reactor.
  • the gas is injected through the needle b102 to increase the pressure in the disposable reaction bottle 2 and the content in the 2 disposable reaction bottles is retrieved through the needle a101.
  • One end of the mass transfer line can be connected to a disposable reagent bottle, and the other end is connected to the needle a101 of the disposable liquid pipeline; the other end of the needle a101 can be directly or pierced through the pierceable member 201 and extended into the disposable reactor 2.
  • the fixing member 103 is composed of a sealing member 1031 and a ring 1032, and the bottom of the ring 1032 is fixedly connected to the sealing member 1031.
  • the needle a101 is 7-shaped, one end passes through the side wall of the ring 1032, and the other end passes through the seal 1031; the end of the needle b102 inside the ring 1032 is lower than the height of the ring, and the other end of the needle b102 is shorter than the same Side needle a101.
  • the needle b102 is shorter in the reaction bottle 2 than the needle a101, which is more conducive to discharging or injecting gas.
  • Disposable reagent bottles, disposable liquid pipes 1, disposable reactor 2 can be removed after use.
  • the invention also provides a tracer synthesizer, which comprises the above-mentioned disposable reaction device, a connecting member 3 and a needle c4, and one end of the needle c4 passes through the connecting member 3.
  • the upper port of the ring 1032 is in contact with the bottom of the connecting member 3, and the fixing member 103 is connected to the connecting member 3 by applying external air pressure. After the air pressure is released, the fixing member 103 can be separated from the connecting member 3.
  • the invention also provides a method for producing a tracer by the above synthesizer, comprising the following steps:
  • the filling element is connected to the connector 3 after externally applying air pressure; the mobile device sends the reaction bottle 2 below the filling element; the filling element moves downward, and the needle 101 and needle 102 pierce the pierceable member 201 and extend into the reaction bottle 2; one end of the mass transfer line is connected to the reagent bottle and one end is connected to the needle 101 of the filling element, and the radioactive isotope and at least one reagent and / or solvent and / or reactant loaded in the disposable reagent bottle are gradually and sequentially from the needle 101 Filling into the disposable reaction bottle 2; filling elements; wherein the mass transfer line is a hollow tube commonly used in the synthesis reaction of the tracer;
  • the moving device sends the reaction bottle 2 below the evaporation element, and the evaporation element moves downward.
  • the needle 101 and the needle 102 pierce the pierceable member 201 and extend into the reaction bottle 2. Nitrogen is blown through the needle 101, and the needle 102 is used for To remove gas and moisture; dry, evaporate or concentrate the contents of the disposable reaction container by the evaporation element, and the evaporation element moves up;
  • the mobile device sends the reaction bottle 2 under the seal 1031, and the seal 1031 is moved down. Instead, the reaction bottle 2 is sealed on the reaction bottle 2, and the reaction bottle 2 is sealed to perform a radiochemical reaction to generate a radiochemical product or a radioactive intermediate for further reaction. Convert radioactive intermediates into radiochemical products; seal 1031 moves up;
  • the moving device sends the reaction bottle 2 below the retracting element, and the retracting element moves downward.
  • the needle 101 and the needle 102 pierce the pierceable member 201 and extend into the reaction bottle 2.
  • the gas is blown through the needle 102 and the reaction bottle 2
  • the contents are retrieved through the needle 1;
  • the involved mobile device and temperature control element may be in various forms and various devices that meet the requirements, and are considered as the prior art.

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Abstract

公开了一次性反应装置，包括一次性试剂瓶，用于装载反应物质，包括放射性同位素、溶剂、试剂、反应物；可直接或通过一次性液体管道（1）将装载物填充到一次性反应器（2）中；一次性反应器（2），用于容纳放射性同位素和至少一种试剂进行反应，通过可刺穿构件（201）密封一次性反应器（2）；一次性液体管道（1），包括蒸发元件、填充元件、收回元件、传质管线。还公开了包括该一次反应装置的示踪剂合成仪及其生产示踪剂的方法。

Description

一次性反应装置和一种示踪剂合成仪及其生产示踪剂方法 技术领域
本发明涉及器械技术领域，尤其涉及一次性反应装置和一种示踪剂合成仪及其生产示踪剂方法。
背景技术
分子影像学近年来发展迅速，PET-CT（正电子发射计算机断层显像）使用正电子放射性示踪剂，在肿瘤、心脏和神经***不同疾病的诊断中可以早期发现疾病。通过回旋加速器制造18F、11C、13N等放射性核素，然后通过化学合成模块（也称合成仪）将这些放射性核素标记到不同的化学底物上，合成最终的供临床使用的各种示踪剂。由于正电子放射性示踪剂具有放射性高、半衰期短的特性，因此全部使用微量试剂通过化学合成仪全自动合成。对于PET-CT显像，目前虽然已经开发出了许多新的正电子放射性药物，但18F-PDG仍然是临床使用最多、应用范围最大的示踪剂。
目前国内外的合成仪在示踪剂的合成过程中，合成一次之后，需要对设备进行清洗，并且等待放射性衰变10个半衰期后才能进行下一次示踪剂的生产，一般这个过程需要超过24小时。这就带来了以下几个问题：
1、时间浪费，需要24小时以上才能进行一次合成。
2、浪费原材料，放射性示踪剂合成过程中，会首先通过加速器产生放射性18F，即使再小的需求量，也必需进行一次轰击，这样就会造成使用率低下，造成成本的增加。
3、可能污染环境威胁人身安全。清洗设备不仅浪费了大量的人力物力，同时清洗液也可能造成环境污染，对工作人员的人身安全也存在威胁。
4、清洗和检查清洗效果需要花费大量的时间，清洗时间和清洗效果直接影响合成的效率。
为了解决上述问题，需要一种不需要清洗、可在短时间内反复进行的放射性示踪剂合成装置。
发明内容
为了解决上述问题，本发明提供了一次性反应装置和一种示踪剂合成仪及其生产示踪剂方法，其中，一种一次性反应装置使用完成后全部可以移除，也就不存在清洗管道等问题，解决了等待、清洗、浪费、污染等相关问题，可以在短时间内重复合成示踪剂，并且更加符合GMP的要求。
本发明提供了一种一次性反应装置，包括：
一次性试剂瓶，用于装载反应所需物质，包括放射性同位素、溶剂、试剂、反应物；可直接或通过一次性液体管道将装载物填充到一次性反应器中；一次性试剂瓶可以是各种形状各种材质，只要符合所装载的物质要求即可，使用完毕后可一般来说都可以很容易移除。
一次性反应器，用于容纳放射性同位素和至少一种试剂进行反应，可以用可刺穿构件密封。
一次性液体管道，包括蒸发元件、填充元件、收回元件，传质管线；其中蒸发元件、填充元件、收回元件均包括针头a、针头b和固定件；针头a和针头b均刺穿并固定在固定件内；其中蒸发元件、填充元件、收回元件结构相同，但是因为用途以及使用方法都不相同，因此，为了能更好的理解本发明，分别给与不同名称。蒸发元件用于干燥，蒸发或浓缩在一次性反应器内的内容物，通过针头a喷入氮气或其他惰性气体，通过针头b排出气体及水分。填充元件用于将一次性试剂瓶中所装载的物质填充到一次性反应器中，通过针头a填充物料，通过针头b排出气体。收回元件用于将反应后中间体或产品移除出一次性反应器，通过针头b喷入气体增加一次性反应瓶内压力，通过针头a收回一次性反应瓶瓶内内容物。传质管线的一端可连接一次性试剂瓶，另一端连接一次性液体管道的针头a；针头a的另一端可直接或者刺穿可刺穿构件后伸入一次性反应器内。所述固定件由密封件和圆环组成，圆环底部固定连接在密封件上。 所述针头a呈7型，一端穿过圆环侧壁，另一端穿过密封件；针头b位于圆环内的一端高度低于圆环的高度，针头b的另一端短于同侧针头a。针头b在反应瓶内短与针头a更利于排出或喷入气体。
一次性试剂瓶、一次性液体管道、一次性反应器使用完毕后均可移除。
所述放射性同位素为氟-18，也可以是常用的11C、13N等放射性核素。
本发明还提供了一种示踪剂合成仪，包括上述一次性反应装置及连接件和针头c，针头c一端穿过连接件。所述圆环的上端口与连接件的底部相抵接，并通过施加外部气压，将固定件与连接件相连接，解除气压后，固定件可与连接件分离。本发明通过外部气压将固定件与连接件相连，而不是通过常用的铆接、螺丝等方式连接，实现了全自动化生产，连接和分离都非常方便，同时，因为放射性示踪剂的生产因为有辐射的原因，都是采用密闭方式生产，如果还需要人工清洗或调换装置，同样需要等待放射性衰变10个半衰期后才能进行，从而产生浪费时间、威胁工作人员的身体健康等问题。当固定件与连件通过外部气压相连接以后，固定件与连接件形成了一个密闭的空间，针头c与针头b虽然中间有断层，但是通过密闭空间相连，形成了完整的通道，可以往反应瓶里填充气体，也可以从反应瓶往外排气，因为针头c没有直接与针头b相连，因此针头c和连接件并没有接触到反应物，反应完毕后不需要移除，从而可以简化步骤、减少成本。
本发明还提供了一种上述合成仪生产示踪剂的方法，包括以下步骤：
（a）通过传质管线及填充元件将一次性试剂瓶中装载的放射性同位素及至少一种试剂和/或溶剂和/或反应物按顺序、逐步填充入一次性反应瓶中；
（b）通过蒸发元件将一次性反应容器中的内容物干燥，蒸发或浓缩；
（c）进行放射化学反应，产生放射性化学产物或放射性中间体进一步反应将放射性中间体转化为放射化学产物； 
（d）通过收回元件及传质管线从反应容器中取回放射化学产物或放射性中间体；
（e）移除填充元件、蒸发元件、收回元件、传质管线和一次性反应器。
与现有技术相比，本发明带来的有益效果是：
1、不需要等待放射性衰变10个半衰期后才进行下一次示踪剂的生产，一次性反应装置使得相同或不同的示踪剂合成可以在短时间内反复进行，极大的提升了示踪剂的研究和生产的效率。
2、不需要清洗，极大的节约了时间、人力物力。
3、消除了因清洗液对环境造成的污染，以及因对清洗人员造成的人身安全威胁。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以 根据这些附图获得其他的附图。
本发明的细节，其结构和操作都可以部分地通过附图获得，其中相同的附图标记表示相同的部分，并且箭头表示移动部件的移动方向。
图1为非一次性填充元件填充的过程；
图2为非一次性取出原件取出的过程；
图3为本发明中一次性填充元件填充的过程；
图4为本发明中一次性取出原件取出的过程；
图中标号为：一次性液体管道（1），针头a（101），针头b（102），固定件（103），密封件（1031），圆环（1032），一次性反应瓶（2），可刺穿构件（201），连接件（3），针头c（4）。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
放射性示踪剂合成需要放射性同位素和至少一种试剂。放射性示踪剂合成可涉及一个或多个反应步骤，产生放射性中间产物或放射化学产物，其可被纯化为示踪剂。放射性示踪剂合成仪也涉及多个装置，如产生放射性核素的加速器、提供能量的温度控制元件、安装或移除装置的移动装置等，本发明为涉及其合成步骤的一次性反应装置，放射性示踪剂生产过程中涉及的其他步骤、其他装置均视为本领域技术人员所掌握的现有技术，不在此赘述。本发明可以以许多不同的形式来实施，并且不应该被解释为限于在此阐述的实施例。相反，提供这些实施例是为了确保本公开是彻底和完整的，并且确保它将本发明的范围完全传达给本领域技术人员。
实施例1
如附图1所示，现有示踪剂合成仪中使用的非一次性填充元件填充的过程为：反应瓶2移动到液体管道1下方，液体管道1下移，反应所需物质通过针头a101填充到反应瓶2内，通过针头b102排气，反应完毕，液体管道1上移。
反应完毕后，经过蒸发过程，反应瓶2再移动到其他液体管道下方，准备进行取出反应瓶2内内容物的步骤，附图2所示，反应瓶2移动到其他液体管道1下方，液体管道1下移，通过针头b102喷入气体，再通过针头1将内容物取出。
从图1和图2可以看到，液体管道1由密封件1031和穿过密封件1031的针头a101、针头b102组成，液体管道1在反应的过程中收到了放射性核素和反应液体的污染，但又非一次性装置，如果需要进行下一次反应，液体管道1、反应瓶2等设备均需要清洗、等待放射性衰变10个半衰期后才进行下一次示踪剂的生产。
实施例2
本发明提供了一种一次性反应装置，包括：
一次性试剂瓶，可以是多个的，分别装载放射性同位素、溶剂、试剂、反应物；可通过一次性液体管道1将一次性试剂瓶内装载物按顺序、逐步填充到一次性反应器2中。
一次性反应器2，用于容纳放射性同位素和至少一种试剂进行反应，可以用可刺穿构件201密封。虽然反应时有密封件1031进行密封，但是增加可刺穿构件201密封以后，可以在液体管道1移开以后保持密封状态，放射性核素辐射造成的影响。
一次性液体管道1，包括蒸发元件、填充元件、收回元件，传质管线；其中蒸发元件、填充元件、收回元件均包括针头a101、针头b102和固定件103；针头a101和针头b102均刺穿并固定在固定件103内；蒸发元件用于干燥，蒸发或浓缩在一次性反应器内的内容物，通过针头a101喷入氮气或其他惰性气体，通过针头b102排出气体及水分。填充元件用于将一次性试剂瓶中所装载的物质填充到一次性反应器中，通过针头a101填充物料，通过针头b102排出气体。收回元件用于将反应后中间体或产品移除出一次性反应器，通过针头b102喷入气体增加一次性反应瓶2内压力，通过针头a101收回一次性反应瓶2瓶内内容物。传质管线的一端可连接一次性试剂瓶，另一端连接一次性液体管道的针头a101；针头a101的另一端可直接或者刺穿可刺穿构件201后伸入一次性反应器2内。所述固定件103由密封件1031和圆环1032组成，圆环1032底部固定连接在密封件1031上。 所述针头a101呈7型，一端穿过圆环1032侧壁，另一端穿过密封件1031；针头b102位于圆环1032内的一端高度低于圆环的高度，针头b102的另一端短于同侧针头a101。针头b102在反应瓶2内短与针头a101更利于排出或喷入气体。
一次性试剂瓶、一次性液体管道1、一次性反应器2使用完毕后均可移除。
实施例3
本发明还提供了一种示踪剂合成仪，包括上述一次性反应装置及连接件3和针头c4，针头c4一端穿过连接件3。所述圆环1032的上端口与连接件3的底部相抵接，并通过施加外部气压，将固定件103与连接件3相连接，解除气压后，固定件103可与连接件3分离。
实施例4
本发明还提供了一种上述合成仪生产示踪剂的方法，包括以下步骤：
（a）填充元件通过外部施加气压后与连接件3连接；移动装置将反应瓶2送到填充元件下方；填充元件下移，针头101和针头102刺穿可刺穿构件201后伸入反应瓶2内；传质管线一端连接试剂瓶，一端连接填充元件的针头101，将一次性试剂瓶中装载的放射性同位素及至少一种试剂和/或溶剂和/或反应物逐步、按顺序从针头101填充入一次性反应瓶2中；填充元件；其中传质管线为示踪剂合成反应中常用的中空管；
（b）移动装置将反应瓶2送到蒸发元件下方，蒸发元件下移，针头101和针头102刺穿可刺穿构件201后伸入反应瓶2内，通过针头101吹入氮气，针头102用于排除气体和水分；通过蒸发元件将一次性反应容器中的内容物干燥，蒸发或浓缩，蒸发元件上移；
（c）移动装置将反应瓶2送到密封件1031下方，密封件1031下移，改在反应瓶2上，将反应瓶2密封，进行放射化学反应，产生放射性化学产物或放射性中间体进一步反应将放射性中间体转化为放射化学产物；密封件1031上移； 
（d）移动装置将反应瓶2送到收回元件下方，收回元件下移，针头101和针头102刺穿可刺穿构件201后伸入反应瓶2内，通过针头102吹入气体，反应瓶2内内容物通过针头1收回；
（e）移除收填充元件、蒸发元件、回收元件、传质管线和一次性反应器2，反应步骤结束。
其中每一步都有不同的温度控制单元配合。涉及的移动装置、温度控制元件可以是符合要求的各种形式、各种不同的设备，均视为现有技术。
还需要说明的是，在本文中，诸如第一和第二等之类的关系术语仅仅用来将一个实体或者操作与另一个实体或操作区分开来，而不一定要求或者暗示这些实体或操作之间存在任何 这种实际的关系或者顺序。而且，术语“包括”、“包含”或者其任何其他变体意在涵盖非排他性的包含，从而使得包括一系列要素的过程、方法、物品或者设备不仅包括那些要素，而且还包括没有明确列出的其他要素，或者是还包括为这种过程、方法、物品或者设备所固有的 要素。在没有更多限制的情况下，由语句“包括一个……”限定的要素，并不排除在包括所述 要素的过程、方法、物品或者设备中还存在另外的相同要素。
本说明书中各个实施例采用递进的方式描述，每个实施例重点说明的都是与其他实施例的不同之处，各个实施例之间相同相似部分互相参见即可。
对所公开的实施例的上述说明，使本领域专业技术人员能够实现或使用本发明。对这些实施例的多种修改对本领域的专业技术人员来说将是显而易见的，本文中所定义的一般原理可以在不脱离本发明的精神或范围的情况下，在其它实施例中实现。因此，本实用
新型将不会被限制于本文所示的这些实施例，而是要符合与本文所公开的原理和新颖特点相一致的最宽的范围。

Claims (7)

  1. 一种一次性反应装置，包括：
    一次性试剂瓶，用于装载反应所需物质，包括放射性同位素、溶剂、试剂和反应物；所述一次性试剂瓶能够直接或通过一次性液体管道（1）将装载反应所需物质填充到一次性反应器（2）中；
    一次性反应器（2），用于容纳放射性同位素和至少一种试剂进行反应；所述一次性反应器（2）通过可刺穿构件（201）进行密封；
    一次性液体管道（1），包括针头a（101）、针头b（102）、固定件（103）和传质管线；
    所述针头a（101）和针头b（102）相互并排设置，且针头a（101）和针头b（102）向下均刺穿并固定在固定件（103）内；
    所述传质管线的一端连接一次性试剂瓶，另一端连接一次性液体管道上的针头a（101）的一端；
    所述针头a（101）的另一端直接或者刺穿通过可刺穿构件（201）后伸入一次性反应器（2）内。
  2. 根据权利要求1中所述的一种一次性反应装置，其特征在于，所述固定件（103）包括密封件（1031）和圆环（1032），圆环（1032）底部固定连接在密封件（1031）上。
  3. 根据权利要求2中所述的一种一次性反应装置，其特征在于，所述针头a（101）呈“ ┐”字型，针头a（101）的一端向外穿过圆环（1032）侧壁，另一端向下穿过密封件（1031）；针头b（102）位于圆环（1032）内的一端高度低于圆环的高度，针头b（102）的另一端短于同侧针头a（101）。
  4. 根据权利要求1、2或3中所述的一种一次性反应装置，其特征在于，所述放射性同位素为氟-18。
  5. 一种示踪剂合成仪，包括根据权利要求1、2或3中所述的一次性反应装置，还包括连接件（3）和针头c（4），针头c（4）一端穿过连接件（3）。
  6. 根据权利要求5中所述的一种示踪剂合成仪，其特征在于，所述圆环（1032）的上端口与连接件（3）的底部相抵接，并通过施加外部气压，将固定件（103）与连接件（3）相连接，解除气压后，固定件（103）能够与连接件（3）分离。
  7. 一种根据权利要求5所述合成仪生产示踪剂的方法，其特征在于，包括以下步骤：
    （a）通过传质管线及填充元件将一次性试剂瓶中装载的放射性同位素及至少一种试剂和/或溶剂和/或反应物按顺序、逐步填充入一次性反应瓶（2）中；
    （b）通过蒸发元件将一次性反应容器中的内容物干燥，蒸发或浓缩；
    （c）进行放射化学反应，产生放射性化学产物或放射性中间体进一步反应将放射性中间体转化为放射化学产物； 
    （d）通过收回元件及传质管线从反应容器中取回放射化学产物或放射性中间体；
    （e）移除填充元件、蒸发元件、收回元件、传质管线和一次性反应器（2）；
    其中：蒸发元件、填充元件、收回元件均包括针头a（101）、针头b（102）和固定件（103）；
    所述蒸发元件用于干燥，蒸发或浓缩在一次性反应器内的内容物，通过针头a（101）喷入氮气，通过针头b（102）排出气体及水分；
    所述填充元件用于将一次性试剂瓶中所装载的物质填充到一次性反应器中，通过针头a（101）填充物料，通过针头b（102）排出气体；
    所述收回元件用于将反应后中间体或产品移除出一次性反应器，通过针头b（102）喷入气体增加一次性反应瓶（2）内压力，通过针头a（101）收回一次性反应瓶（2）瓶内内容物。
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