CN209144051U - One kind is for synthesizing18The system of the red nitroimidazole of F- fluorine - Google Patents

Abstract

The utility model relates to one kind for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, it is characterized in that, including target water receiving flask, No. 1~No. 5 reagent bottles, cutting ferrule, QMA column, reaction flask, half preparative high-performance liquid chromatographic instrument and controller, cutting ferrule includes that pipe network and several folders close device, if pipe network is made of trunk pipeline and several interfaces, target water receiving flask, No. 1~No. 5 reagent bottles pass through pipeline respectively and are connected with an interface；Each folder closes device and is connected respectively with controller, and controller passes through controls each unlatching/closing pressed from both sides and close device respectively, disconnects target water receiving flask, No. 1~No. 5 reagent bottles and reaction flask are sequentially communicated/；This system can be with synthesis¹⁸The process of the red nitroimidazole of F- fluorine is adapted, and process is succinct, easy to operate, can large dosage, high-purity, be efficiently completed¹⁸The synthetic work of the red nitroimidazole of F- fluorine, not only can be effectively reduced the failure rate of synthesis, but also may be implemented¹⁸The Fully automated synthesis of the red nitroimidazole of F- fluorine.

Description

One kind is for synthesizing18The system of the red nitroimidazole of F- fluorine

Technical field

The utility model relates to radiochemistry technical field of medicine synthesis, and in particular to one kind is for synthesizing¹⁸The red nitre of F- fluorine The system of base imidazoles.

Background technique

A variety of methods for directly or indirectly measuring tissue oxygen levels are currently, there are, but due to traumatic or technical Difficulty, be difficult clinically to be widely applied；Therefore, how in time, accurately to reflect that weary oxygen situation is increasingly becoming shadow in recent years As the hot spot of medicine and oncology studies.It is existing studies have shown that using reflexive nucleic, such as¹⁸F, the small molecule imaging of label Agent, which carries out PET imaging, can carry out qualitative and quantitative detection to weary oxygen, have the characteristics that non-invasive, quantitative, repeatable, be Technology the most advanced is studied in weary oxygen detection at present.

PET hypoxia imaging the most commonly used is¹⁸F- fluorine nitroimidazole (abbreviation FMISO), but there are still one for FMISO-PET detection A little disadvantages, for example, absorbance of tissue is relatively low, normal tissue elution is slower, has certain neurotoxicity etc.；In recent years, to mention The water solubility of high imaging agent, to improve imaging results and reduce its toxicity, researcher develops from the derivative of FMISO A kind of novel anoxia developing agent:¹⁸The red nitroimidazole of F- fluorine is (referred to as¹⁸F-FETNIM),¹⁸The bio distribution of the red nitroimidazole of F- fluorine Researches show that its surrounding tissue metabolic rate, defluorinate rate, water solubility and hypoxic tissue metabolic rates to be suitable for PET hypoxia imaging.Cause This, in clinical and scientific research, the demand to this Novel PET imaging agent is increasingly urgent to,¹⁸The red nitroimidazole of F- fluorine needs to obtain greatly Dosage, efficiently synthesizes high quality, this is right¹⁸The synthesis technology and system of the red nitroimidazole of F- fluorine propose new, higher want It asks.

Utility model content

The purpose of this utility model is to provide one kind for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, this system can be with With synthesis¹⁸The process of the red nitroimidazole of F- fluorine is adapted, and is conducive to large dosage, high-purity, is efficiently completed¹⁸F- fluorine is red The synthetic work of nitroimidazole, and the failure rate of synthesis can be effectively reduced.

The technical scheme adopted by the utility model is

One kind is for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, including target water receiving flask, No. 1 reagent bottle, No. 2 reagent bottles, No. 3 reagent bottles, No. 4 reagent bottles, No. 5 reagent bottles, cutting ferrule, QMA column, reaction flask, temperature controller one, vacuum pump, half prepare height Effect liquid phase chromatogram instrument and controller, wherein

The target water receiving flask has for containing¹⁸F^-Target water, No. 1 reagent bottle is for containing K222 and K₂CO₃'s Mixed solution, No. 2 reagent bottles are for containing anhydrous acetonitrile, and No. 3 reagent bottles are for containing precursor solution, and described No. 4 Reagent bottle is for containing hydrochloric acid, and No. 5 reagent bottles are for containing sodium hydroxide solution；

The cutting ferrule includes that pipe network and several folders close device, if the pipe network is made of trunk pipeline and several interfaces, the target Water receiving flask, No. 1 reagent bottle, No. 2 reagent bottles, No. 3 reagent bottles, No. 4 reagent bottles and No. 5 reagent bottles pass through pipeline and one respectively A interface is connected；

The both ends of the QMA column pass through pipeline respectively and are connected with two interfaces in the pipe network, and QMA column is for capturing In target water¹⁸F^-；

The reaction flask is connected by pipeline with an interface in the pipe network, and reaction flask is for being reacted；

The vacuum pump is connected by pipeline with an interface in the pipe network, and is connected with the controller, very Sky pump for generating negative pressure under the control of the controller, to carry out negative pressure transportation；

The sample injector of the half preparative high-performance liquid chromatographic instrument is connected by pipeline with an interface of the pipe network, institute Half preparative high-performance liquid chromatographic instrument is stated for isolating and purifying to the product of collection；

The temperature controller one is set at the reaction flask, and is connected with the controller, in controller Control the temperature of lower adjusting reaction flask；

Each folder closes device and is connected respectively with the controller, and the controller closes opening for device by controlling each folder respectively Open/close so that target water receiving flask, No. 1 reagent bottle, No. 2 reagent bottles, No. 3 reagent bottles, No. 4 reagent bottles and No. 5 reagent bottles with The reaction flask is sequentially communicated/disconnects.

In a kind of preferred scheme, the pipe network includes 13 pipelines and 16 interfaces, and 13 pipelines are hose, Wherein,

Interface one is connected with interface nine by the first pipeline, and interface two is connected by the second pipeline with first pipeline Logical, interface eight is connected with interface 14 by third pipeline, and interface three is connected by the 4th pipeline with the third pipeline, Interface four is connected by the 5th pipeline with the 4th pipeline, and interface five is connected by the 6th pipeline with the 4th pipeline Logical, interface seven is connected by the 7th pipeline with the 4th pipeline, and interface six is connected by the 7th pipeline described in the 8th pipeline Logical, interface ten is connected by the 9th pipeline with first pipeline, and interface 12 passes through the tenth pipeline and the interface 13 It is connected, interface 11 is connected by the 11st pipeline with the tenth pipeline, and interface 15 passes through the 12nd pipeline and connects Mouth 16 is connected, and the 13rd pipeline is connected with the 4th pipeline and the tenth pipeline respectively；The pipeline of each interface On be respectively arranged with it is described folder close device；

The target water receiving flask is connected with the interface one, and No. 1 reagent bottle is connected with the interface two, described No. 2 reagent bottles are connected with the interface three, and No. 3 reagent bottles are connected with the interface four, No. 4 reagent bottles and institute It states interface six to be connected, No. 5 reagent bottles are connected with the interface seven；The half preparative high-performance liquid chromatographic instrument with it is described Interface eight is connected, and the QMA column is connected with the interface ten and interface 11 respectively, the interface 13, interface 14 And interface 15 is connected with the reaction flask respectively, the interface five, interface nine and interface 16 respectively with it is described true Sky pump is connected.

Preferably, each pipeline in the pipe network is hose.

In a kind of preferred scheme, it is pinch valve that the folder, which closes device,.

Optionally, it is electromagnetism pinch valve that the folder, which closes device,.

Further, the electromagnetism pinch valve is closed type electromagnetism pinch valve.

It further, further include outstanding steaming bottle, No. 6 reagent bottles, filter and product receiving flask, wherein the outstanding steaming bottle It is connected by pipeline with the output end of the half preparative high-performance liquid chromatographic instrument, the product receiving flask and No. 6 reagent bottle difference It is connected by pipeline with the outstanding steaming bottle, the filter is set on the outstanding pipeline steamed between bottle and product receiving flask, No. 6 examinations For agent bottle for containing physiological saline, filter enters filtrate in the product receiving flask for being filtered.

Preferably, in No. 6 reagent bottles, the amount of the physiological saline is 10mL.

Further, further include No. 7 reagent bottles and temperature controller two, No. 7 reagent bottles by triple valve be connected to The pipeline of outstanding steaming bottle and half preparative high-performance liquid chromatographic instrument is connected, and No. 7 reagent bottles are for containing ethyl alcohol, the triple valve and institute Controller is stated to be connected；The temperature controller two is set at the outstanding steaming bottle, and is connected with the controller, for controlling Outstanding steaming bottle is heated under the control of device.

Further, the temperature controller one and temperature controller two further include temperature sensor respectively, the temperature Sensor is used to detect reaction flask and the outstanding temperature for steaming bottle, and is transferred to controller；So as to controller precise control of temperature.

It further, further include target water returnable bottle, the target water returnable bottle is connected by pipeline with the interface 12, It is lost for being connected under the control of the controller with the QMA column, and for collecting¹⁸F^-Target water afterwards.

It further, further include booster pump, the booster pump passes through pipeline respectively and the target water receiving flask, target water recycle Bottle, No. 6 reagent bottles, No. 7 reagent bottles, outstanding bottle, interface five, interface nine and the interface 16 of steaming are connected, booster pump and the control Device processed is connected, and booster pump has the nitrogen of certain pressure for input under the control of the controller, to carry out pressure to reagent Conveying.

It further, further include radio-metric probe, the radio-metric probe is respectively arranged at the QMA column and the reaction At bottle, and it is connected respectively with the controller, is set to the radio-metric probe at QMA column for detecting in target water¹⁸F^-Whether It is all adsorbed on QMA column, is set to the radio-metric probe at reaction flask for detecting on QMA column¹⁸F^-Whether all elution Into reaction flask.

It further, further include display and camera, the camera is respectively arranged at the reaction flask, half preparation height At the sample injector of effect liquid phase chromatogram instrument and the outstanding steaming bottle, the display and each camera respectively with the controller phase Even, camera is respectively used to acquisition reaction flask, sample injector and the outstanding image information for steaming bottle, and is shown using display.

Compared with prior art, using provided by the utility model a kind of for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, It can be with synthesis¹⁸The process of the red nitroimidazole of F- fluorine is adapted, and process is succinct, easy to operate, can be large dosage of, high-purity It spends, be efficiently completed¹⁸The synthetic work of the red nitroimidazole of F- fluorine, not only can be effectively reduced the failure rate of synthesis, but also can be with It realizes¹⁸The Fully automated synthesis of the red nitroimidazole of F- fluorine.

Detailed description of the invention

It, below will be to use required in embodiment in order to illustrate more clearly of the technical solution of the utility model embodiment Attached drawing be briefly described, it should be understood that the following drawings illustrates only some embodiments of the utility model, therefore should not be by Regard the restriction to range as, for those of ordinary skill in the art, without creative efforts, may be used also To obtain other relevant attached drawings according to these attached drawings.

Attached drawing

Fig. 1 is a kind of synthesis provided in the utility model embodiment 1¹⁸The process flow diagram of the red nitroimidazole of F- fluorine.

Fig. 2 is that during the preparation process, crude product prepares the peak figure out isolated and purified on HPLC half.

Fig. 3 be product standard product (i.e.¹⁸The red nitroimidazole of F- fluorine) analyzing the uv-spectrogram on HPLC.

Fig. 4 be the product that is prepared using method provided by embodiment 1 (i.e.¹⁸The red nitroimidazole of F- fluorine) on analysis HPLC Radiation map.

Fig. 5 be the product that is prepared using method provided by embodiment 1 (i.e.¹⁸The red nitroimidazole of F- fluorine) on analysis HPLC Uv-spectrogram.

Fig. 6 is that the one kind provided in the utility model embodiment 2 is used to synthesize¹⁸The structure of the system of the red nitroimidazole of F- fluorine Schematic diagram.

Description of symbols in figure

The reagent bottle 104,4 reagent bottle 105,5 of reagent bottle 103,3 of reagent bottle 102,2 of target water receiving flask 101,1 Reagent bottle 106, cutting ferrule 107, QMA column 108, reaction flask 109, temperature controller 1, vacuum pump 111, half prepares efficient liquid phase Chromatograph 112, valve 113,

Outstanding steaming 201, No. 6 reagent bottles 202 of bottle, filter 203, product receiving flask 204,

No. 7 reagent bottles 301, temperature controller 2 302, triple valve 303,

Booster pump 401, target water returnable bottle 402, radio-metric probe 403,

Interface 1, interface 22, interface 33, interface 44, interface 55, interface 66, interface 77, interface 88, interface 99, interface 10, interface 11, interface 12, interface 13, interface 14, interface 15, interface 16 16,

First pipeline 501, the second pipeline 502, third pipeline 503, the 4th pipeline 504, the 5th pipeline 505, the 6th pipeline 506, the 7th pipeline 507, the 8th pipeline 508, the 9th pipeline 509, the tenth pipeline 510, the 11st pipeline 511, the 12nd pipeline 512, the 13rd pipeline 513,

Folder closes device 1, and folder closes device 2 602, and folder closes device 3 603, and folder closes device 4 604, and folder closes device 5 605, and folder closes device six 606, folder closes device 7 607, and folder closes device 8 608, and folder closes device 9 609, and folder closes device 10, and folder closes device 611, and folder closes device 1, presss from both sides Device 2 613 is closed, folder closes device 3 614, and folder closes device 4 615, and folder closes device 616.

Specific embodiment

Below in conjunction with attached drawing in the utility model embodiment, the technical scheme in the embodiment of the utility model is carried out clear Chu is fully described by, it is clear that the described embodiments are only a part of the embodiments of the utility model, rather than whole realities Apply example.The component of the utility model embodiment being usually described and illustrated herein in the accompanying drawings can be come with a variety of different configurations Arrangement and design.Therefore, the detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit below The range of claimed invention, but it is merely representative of the selected embodiment of the utility model.Based on the utility model Embodiment, those skilled in the art's every other embodiment obtained without making creative work, all Belong to the range of the utility model protection.

Embodiment 1

A kind of synthesis is provided in the present embodiment¹⁸The method of the red nitroimidazole of F- fluorine, includes the following steps:

Firstly, utilizing precursorWith¹⁸F^-Nucleophilic substitution is carried out, intermediate product is generated；

Then, Xiang Suoshu intermediate product is added hydrochloric acid and reaction is hydrolyzed, and obtains hydrolysate Obtaining hydrolysate at this time is¹⁸The red nitroimidazole of F- fluorine is (i.e.¹⁸F-FETNIM is repeated no more hereinafter) crude product, it needs further Purification process；

Finally, the hydrolysate is isolated and purified by half preparation HPLC, it is hereby achieved that purity is higher¹⁸F-FETNIM product；

Wherein, the half preparation HPLC, using water, acetonitrile and ethyl alcohol as mobile phase, appearance time is 6~7min.

Preparation method provided by the present embodiment is simple, efficient, is synthesized using this method¹⁸F-FETNIM, not only can be big Dosage, high-purity, efficient synthesis¹⁸F-FETNIM, and since synthesis process is succinct, each step is controllable, so as to have Effect reduces the failure rate of synthesis.

As shown in Figure 1, specifically, in a kind of preferred scheme provided by the present embodiment, it is specific to synthesize¹⁸F- fluorine Red nitroimidazole is (i.e.¹⁸F-FETNIM process flow) are as follows:

Step 1, QMA capture: it can use in 108 acquisition target water of QMA column¹⁸F^-, and make¹⁸F^-It is adsorbed on QMA column 108 On.

As an example, in preferred scheme, in the step 1, it can use booster pump and positive pressure applied to nitrogen, pass through nitrogen Gas extruding has¹⁸F^-Target water, make target water by QMA column 108, during target water passes through QMA column 108, in target water¹⁸F^- It can be adsorbed on QMA column 108, thus will¹⁸F^-It is separated from target water.

Step 2,¹⁸F^-Release: utilize K222 and K₂CO₃Mixed solution will be on QMA column 107¹⁸F^-Elute reaction flask In 109；For example, K222 and K can be made₂CO₃Mixed solution by QMA column 108, and by QMA column 108 during passing through On¹⁸F^-It elutes in reaction flask 109；So as to will be on QMA column 108¹⁸F^-It is transferred in reaction flask 109；

In this step, K222 and K₂CO₃Mixed solution be by K222 solution and K₂CO₃Gained after solution is mixed Solution, wherein the amount of K222 solution can be 0.7mL, K₂CO₃The amount of solution can be 0.2mL.

In the preferred scheme, the preparation method of K222 solution, which may is that, is dissolved in the anhydrous second of 7mL for 220mg K222 powder In nitrile, to obtain K222 solution；The preparation method of K2CO3 solution is: by 58.5mg K₂CO₃Powder is dissolved in 2mL water, thus K2CO3 solution can be obtained.

Step 3, for the first time drying: heating the reaction flask 109, and heating temperature is 100 DEG C, will pass through heating Evaporate K222 and K₂CO₃Mixed solution in water；

As an example, in the present embodiment, it can use booster pump and be pressed into nitrogen instead by one end of reaction flask 109 Answer and form positive pressure in bottle 109, meanwhile, another termination vacuum pump 111 of reaction flask 109 formed negative pressure, then again to reaction flask 109 into Row heating, in this process, heat that evaporated moisture can be convenient as the direction of pressure drop is mobile, thus from reaction It is discharged in bottle 109.

The addition of step 4, acetonitrile: appropriate anhydrous acetonitrile is added in Xiang Suoshu reaction flask 109.

Preferably, in this step, the amount of the anhydrous acetonitrile can be 0.5mL.

Step 5, second of drying: the reaction flask 109 is heated again, to evaporate in reaction flask 109 Water.

As an example, it is preferred that in this step, the temperature of heating can preferentially use 95 DEG C, thoroughly to remove dereaction Water in bottle 109, it is ensured that reacts in next step is normally carried out.

The addition of step 6, precursor: precursor is added in Xiang Suoshu reaction flask 109Solution.It is preferred that , what is be added into reaction flask 109 is precursorAcetonitrile solution；As an example, the present embodiment is mentioned In a kind of preferred scheme supplied, the precursorThe preparation method of solution are as follows: by 2mg precursorIt is dissolved in the anhydrous acetonitrile of 1mL, it is hereby achieved that the precursor's Acetonitrile solution as an example in the present embodiment, can be preferentially using the precursor of German ABX's productionSolution.

Step 7, fluorination: the reaction flask 109 is closed, and the reaction flask 109 is heated, so that reaction flask The precursor in 109 with¹⁸F^-Nucleophilic substitution is carried out, replaces the p-toluenesulfonyl in precursor, and generate intermediate product；

Preferably, in this step, to meet reaction condition, reaction flask 109 should be heated to 95 DEG C or so, heating time It is 8 minutes or so, to ensure that reacts is normally carried out.

The addition of step 8, hydrochloric acid: appropriate certain density hydrochloric acid is added in Xiang Suoshu reaction flask 109.

Preferably, in this step, the concentration of the hydrochloric acid can be 2M, and the hydrochloric acid in the reaction flask 109 is added Amount can be 0.9mL.

Step 9, hydrolysis: reaction flask 109 is heated, so that the intermediate product in reaction flask 109 and the salt Reaction is hydrolyzed in acid, and obtains hydrolysate

Preferably, in this step, to optimize reaction condition, the reaction flask 109 needs to be heated to 90 DEG C or so, adds The hot time is 5min or so, so that it is guaranteed that reaction is normally carried out, specific reaction process is as follows:

At this point, obtained¹⁸The red nitroimidazole of F- fluorine is crude product, it is also necessary to is further processed.

Step 10 adjusts pH value: a certain amount of sodium hydroxide solution being added in Xiang Suoshu reaction flask 109, to adjust reaction The pH value of solution in bottle 109, that is, adjust the pH value of crude product.

Preferably, in the present embodiment, as an example, the concentration of the sodium hydroxide solution can be 2M, sodium hydroxide The amount of solution can be 0.8mL.

Step 11, sample introduction: the solution in the reaction flask 109 being transferred in the sample injector of half preparation liquid phase, and from institute It states in sample injector and the solution is drawn into syringe, complete sample introduction；

In this step, nitrogen can be pressed into reaction flask 109, and gives positive pressure, so as to easily make to react Crude product in bottle 109 is transferred completely into the sample injector of half preparation liquid phase；Then crude product injection half is made by syringe In standby liquid phase, to complete sample introduction work.

Step 12, HPLC are isolated and purified: the separation condition of the half preparation liquid phase is: using YMC-PACK-ODS-AM half Preparative scale chromatography column；The volume ratio of water, acetonitrile and ethyl alcohol is 500:90:10, flow velocity 4.0mL/min, and ultraviolet wavelength is 325nm；When liquid chromatogram curve just radioactivity peak will occur (when i.e. liquid chromatogram curve is begun to ramp up), start to collect¹⁸F- The red nitroimidazole of fluorine, and will be collected by pipeline¹⁸The red nitroimidazole of F- fluorine inputs revolving bottle, when liquid chromatogram curve When radioactivity peak is reduced to baseline, stop collecting¹⁸The red nitroimidazole of F- fluorine, as shown in Fig. 2, can be put after the step Penetrate the higher product of chemical purity (¹⁸The red nitroimidazole of F- fluorine), as shown in Fig. 3, Fig. 4 and Fig. 5, by comparison diagram 3, Fig. 4 with And Fig. 5 not only can be synthesized effectively it is found that using technique provided by this method¹⁸The red nitroimidazole product of F- fluorine, Er Qiesuo Synthesis¹⁸The radiochemical purity of the red nitroimidazole of F- fluorine is very high, is very beneficial for imaging；

Those skilled in the art is perfectly clear the process and operation that HPLC is isolated and purified, and is not discussed here.

Step 13 is rinsed: being rinsed the pipeline using ethyl alcohol, is made remaining in pipeline¹⁸The red nitroimidazole of F- fluorine is rinsed Into the revolving bottle 201；

It is usually necessary to use pipelines by the transferred product after HPLC is isolated and purified into revolving bottle 201, must in pipeline So meeting residual fraction product, causes to waste, therefore in this step, using ethyl alcohol flushing pipe, production can be reduced to greatest extent The loss of product fully enters the product being attached on duct wall in revolving bottle 201.

Step 14, outstanding steaming: the revolving bottle 201 is heated to 180 DEG C, and is rotated, revolving is for removing for rushing The acetonitrile of pipeline is washed, product is further purified in realization.

Step 15, product collect: saline injection in Xiang Suoshu revolving bottle, and make dissolved with¹⁸The red nitroimidazole of F- fluorine The physiological saline is filtered by filter membrane, and collects filtrate, and filtrate is to synthesize to obtain¹⁸The red nitroimidazole of F- fluorine；Through This step is crossed, it is higher to help to obtain purity¹⁸The red nitroimidazole of F- fluorine.

¹⁸The red nitroimidazole of F- fluorine can be dissolved in physiological saline, and as an example, the amount of physiological saline can be 10mL, and In preferred embodiment provided by the present embodiment, the filter membrane can preferentially use the sterilised membrane filter of 0.22um.

Further, in the prioritization scheme provided by the present embodiment, in the step 2¹⁸F^-Release, second in step 4 The addition of hydrochloric acid be realized by the way of being sucked using negative pressure in the addition and step 8 of precursor in the addition of nitrile, step 6, Required reagent is added in reaction flask 109 by the way of negative pressure sucking, it is very convenient.

Embodiment 2

A kind of synthesis according to provided in embodiment 1 of the present embodiment 2¹⁸The method of the red nitroimidazole of F- fluorine, provides one Kind is for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine；

The system mainly includes 103, No. 3 reagent bottles 104,4 of reagent bottle of reagent bottle 102,2 of target water receiving flask 101,1 Number reagent bottle 105, No. 5 reagent bottles 106, cutting ferrule 107, QMA column 108, reaction flask 109, temperature controllers 1, vacuum pump 111, half preparative high-performance liquid chromatographic instrument 112 and controller, as shown in Figure 6, wherein

The target water receiving flask 101 has for containing¹⁸F^-Target water, No. 1 reagent bottle 102 for contain K222 with K₂CO₃Mixed solution, No. 2 reagent bottles 103 are for containing anhydrous acetonitrile, and No. 3 reagent bottles 104 are for containing precursor Solution, No. 4 reagent bottles 105 are for containing hydrochloric acid, and No. 5 reagent bottles 106 are for containing sodium hydroxide solution；

The cutting ferrule 107 includes that pipe network and several folders close device, described if the pipe network is made of trunk pipeline and several interfaces The reagent bottle 103,3 of reagent bottle 102,2 reagent bottle 105 of reagent bottle 104,4 of target water receiving flask 101,1 and No. 5 reagents Bottle 106 is connected by pipeline with an interface respectively；

The both ends of the QMA column 108 pass through pipeline respectively and are connected with two interfaces in the pipe network, and QMA column 108 is used In acquisition target water¹⁸F^-；

The reaction flask 109 is connected by pipeline with an interface in the pipe network, and reaction flask 109 is anti-for carrying out It answers；

The vacuum pump 111 is connected by pipeline with an interface in the pipe network, and is connected with the controller, Vacuum pump 111 for generating negative pressure under the control of the controller, to be conveyed using negative pressure, i.e., is respectively tried using negative pressure transportation Agent；

The sample injector of the half preparative high-performance liquid chromatographic instrument 112 is connected by pipeline with an interface in the pipe network Logical, the half preparative high-performance liquid chromatographic instrument 112 is for isolating and purifying the product of collection；Utilize high performance liquid chromatograph 112, it can be using semipreparative high performance liquid chromatography (High Performance Liquid Chromatography, letter Claim HPLC) product is isolated and purified.

The temperature controller 1 is set at the reaction flask 109, and is connected with the controller, for controlling The temperature of adjusting reaction flask 109 under the control of device processed；Such as reaction flask 109 is heated, so that the temperature of reaction flask 109 is protected It holds in a certain temperature etc..

Each folder closes device and is connected respectively with the controller, and the controller closes device and/or setting by controlling each folder In unlatching/closing of the valve of pipeline, so that target water receiving flask, No. 1 reagent bottle, No. 2 reagent bottles, No. 3 reagent bottles, No. 4 reagents Bottle and No. 5 reagent bottles are sequentially communicated/disconnect with the reaction flask.So as to according to the step in method provided in embodiment 1 Suddenly it synthesizes or is automatically synthesized¹⁸The red nitroimidazole of F- fluorine, it is hereby achieved that purity is relatively high¹⁸The red nitroimidazole of F- fluorine.

As shown in fig. 6, in further scheme provided by the present embodiment, further include it is outstanding steam 201, No. 6 reagent bottles 202 of bottle, Filter 203 and product receiving flask 204, wherein the outstanding steaming bottle 201 passes through pipeline and half preparative high-performance liquid chromatographic The output end of instrument 112 is connected, and the product receiving flask 204 and No. 6 reagent bottles 202 pass through pipeline and the outstanding steaming bottle 201 respectively It is connected, the filter 203 is set on the outstanding pipeline steamed between bottle 201 and product receiving flask 204, and No. 6 reagent bottles 202 are used for Contain physiological saline, and physiological saline be conveyed to outstanding the steamings bottle 201, filter 203 is used to be filtered, and make filtrate into Enter in the product receiving flask 204；The loss of collected product is lower in product receiving flask 204, and product purity is higher, thus Be conducive to obtain large dosageization, high-purity by the system¹⁸The red nitroimidazole of F- fluorine.

As an example, in the present embodiment, the amount of the physiological saline in No. 6 reagent bottles 202 can be 10mL, physiological saline It is mainly used for dissolving¹⁸The red nitroimidazole of F- fluorine.

As shown in fig. 6, further including No. 7 reagent bottles 301 and temperature control in the further scheme provided by the present embodiment Device 2 302, No. 7 reagent bottles 301 pass through triple valve 303 and the pipeline for being connected to outstanding steaming bottle 201 and high performance liquid chromatograph 112 It is connected, No. 7 reagent bottles 301 are used for flushing pipeline for containing ethyl alcohol, the ethyl alcohol, and the temperature controller 2 302 is arranged At the outstanding steaming bottle 201, for the outstanding steaming bottle 201 of heating under the control of the controller.

Triple valve can be opening/closing in the realization of the controller of controller, and No. 7 reagent bottles 301 may be implemented and hang to steam bottle 201 Connection steams bottle 201 to hang the ethyl alcohol input in No. 7 reagent bottles 301, and during conveying, pipeline is rushed in realization It washes.

Further, the temperature controller 1 and temperature controller 2 302 respectively include temperature sensor, described Temperature sensor is used to detect reaction flask 109 and the outstanding temperature for steaming bottle 201, and is transferred to controller, so that controller carries out temperature Degree is adjusted；As an example, temperature controller 1 and temperature controller 2 302 respectively further comprise heater, to be added Heat.

As shown in fig. 6, it is further, it further include target water returnable bottle 402, the target water returnable bottle 402 passes through pipeline and institute An interface for stating pipe network is connected, and loses for being connected under the control of the controller with the QMA column 108, and for collecting It goes¹⁸F^-Target water afterwards.

As shown in fig. 6, it is further, it further include booster pump 401, the booster pump 401 passes through pipeline and the target respectively Water receiving flask 101, the reagent bottle 301 of reagent bottle 202,7 of target water returnable bottle 402,6 and the outstanding bottle 201 that steams are connected, booster pump 401 are connected with the controller, and booster pump 401 has the nitrogen of certain pressure for input under the control of the controller, so as to Pressure conveying is carried out to reagent.

As shown in fig. 6, it is further, it further include radio-metric probe 403, the radio-metric probe 403 is respectively arranged at institute It states at QMA column 108 and the reaction flask 109, and be connected respectively with the controller, is set to the radioactivity at QMA column 108 and visits First 403 for detecting in target water¹⁸F^-Whether all it is adsorbed on QMA column 108, is set to the radioactivity at reaction flask 109 and visits First 403 for detecting on QMA column 108¹⁸F^-All whether elution is into reaction flask 109.

It further, further include display and camera, the camera is respectively arranged at the reaction flask 109, half system At the sample injector and the outstanding steaming bottle 201 of standby high performance liquid chromatograph 112, the display and each camera respectively with institute It states controller to be connected, camera is respectively used to acquisition reaction flask 109, sample injector and the outstanding image information for steaming bottle 201, and utilizes Display is shown.To facilitating operator remotely to be monitored, so as to the process that strict control synthesizes, for example, can be with Check whether reagent is added in reaction flask 109, whether reaction flask 109 is evaporated, the numerical value of radio-metric probe 403 by camera Whether it is not further added by, and operator can enter back into next step after through camera observation and certain situation, thus It may insure that each step is all gone on smoothly, and then the probability of synthesis failure can be greatly reduced.

As shown in fig. 6, pipe network includes 13 pipelines and 16 interfaces in the preferred embodiment provided by the present embodiment, In,

Interface 1 and interface 99 are connected by the first pipeline 501, and interface 22 passes through the second pipeline 502 and described the One pipeline 501 is connected, and interface 88 is connected with interface 14 by third pipeline 503, and interface 33 passes through the 4th pipeline 504 are connected with the third pipeline 503, and interface 44 is connected by the 5th pipeline 505 with the 4th pipeline 504, interface 55 are connected by the 6th pipeline 506 with the 4th pipeline 504, and interface 77 passes through the 7th pipeline 507 and the 4th pipe Line 504 is connected, and interface 66 is connected by the 7th pipeline 507 described in the 8th pipeline 508, and interface 10 passes through the 9th pipeline 509 are connected with first pipeline 501, and interface 12 is connected by the tenth pipeline 510 with the interface 13, connect Mouth 11 is connected by the 11st pipeline 511 with the tenth pipeline 510, and interface 15 passes through the 12nd pipeline 512 It is connected with interface 16, the 13rd pipeline 513 is connected with the 4th pipeline 504 and the tenth pipeline 510 respectively； It is respectively arranged with the folder on the pipeline of each interface and closes device.

As shown in fig. 6, in the present embodiment, the interface 1 in pipe network is used for the target water receiving flask 101 in connected system, Interface 22 is for being connected to No. 1 reagent bottle 102, and interface 33 is for being connected to No. 2 reagent bottles 103, and interface 44 is for being connected to No. 3 examinations Agent bottle 104, interface 66 is for being connected to No. 4 reagent bottles 105, and interface 77 is for being connected to No. 5 reagent bottles 106, and interface 88 is for connecting Logical half preparative high-performance liquid chromatographic instrument, interface 10 and interface 11 are respectively used to be connected to QMA column 108, and interface 12 is used In connection target water returnable bottle, interface 13, interface 14 and interface 15 are respectively used to connection reaction flask 109, connect Mouth 55, interface 99 and interface 16 are respectively used to connection booster pump and vacuum pump.

The target water receiving flask 101 is connected with the interface 1, No. 1 reagent bottle 102 and 22 phase of interface Connection, No. 2 reagent bottles 103 are connected with the interface 33, and No. 3 reagent bottles 104 are connected with the interface 44, No. 4 reagent bottles 105 are connected with the interface 66, and No. 5 reagent bottles 106 are connected with the interface 77；It is described Half preparative high-performance liquid chromatographic instrument 112 is connected with the interface 88, the QMA column 108 respectively with the interface 10 and connect Mouth 11 is connected, and the interface 13, interface 14 and interface 15 are connected with the reaction flask 109 respectively Logical, the interface 55, interface 99 and interface 16 are connected with the vacuum pump 111 and booster pump 401 respectively；It is described Target water returnable bottle 402 is connected by pipeline with the interface 12.It is described in a kind of scheme provided by the present embodiment Each pipeline in pipe network is hose, to close unlatching/closing that device realizes each pipeline using folder, so that effectively control is each The on/off of pipeline, to meet the needs of each step of synthesis technology.

Preferably, in the present embodiment, folder closes device preferentially using pinch valve (Pinch Valve)；Pinch valve is The executing agency of control hose on/off commonly used in the prior art can use pneumatic, electronic, the manual or drivings side such as surge Formula realizes switch/adjusting effect to hose.As an example, in the present embodiment, folder closes device using electromagnetism pinch valve, electricity Magnetic clutch pipe valve (abbreviation pinch valve) is driven by electromagnetic solenoid, controls open and close by squeezing or unclamping pipeline (hose)；It is situated between Matter only passes through from pipeline, the other component in valve body not with the media contact of chemical corrosivity so that electromagnetism pinch valve It is more economical, be more convenient for controlling, the later period of being more convenient for is replaced.

As an example, a kind of electromagnetism pinch valve provided in this embodiment includes valve body and clamping head, and clamping head is fixed on valve Body is provided with groove port on clamping head；When in use, pipeline is arranged in groove port, when electromagnetism pinch valve is closed, in groove port Pipeline be extruded, pipeline disconnects, and when electromagnetism pinch valve is opened, the pipeline in groove port is not extruded, and pipeline is unimpeded.

Further, the present embodiment can preferentially use closed type electromagnetism pinch valve, and medium blocks in pipeline when power-off, that is, manage Line disconnects；Flow of media when energization, i.e. pipeline are unimpeded.

As shown in fig. 6, in the present embodiment, a folder being respectively arranged on the pipeline of each interface and closes device (in this implementation In example, using closed type electromagnetism pinch valve), for ease of description, as shown in fig. 6, being set at interface one to interface 16 Folder to close device be respectively to press from both sides to close device 1 to folder and close device 16.

As an example, it is synthesized using provided by the present embodiment¹⁸The system of the red nitroimidazole of F- fluorine, and according to embodiment 1 Provided in method synthesis¹⁸During the red nitroimidazole of F- fluorine, controller can pass through valve each in control system and card Respectively folder closes the on/off of device in set, and synthesis process smoothly, conveniently, is accurately run, can not only large dosageization, height The synthesis of purity¹⁸The red nitroimidazole of F- fluorine, and the failure rate of synthesis can be effectively reduced；As an example, it is mentioned in embodiment 1 In the step 1 of confession, it is desirable that using in 108 acquisition target water of QMA column¹⁸F^-, and make¹⁸F^-It is adsorbed on QMA column 108；It is using this System, controller can close device 1 by controlling folder, folder closes device 10, folder closes device 11 and folder closes device 12 and opens It opens, so that target water receiving flask 101, QMA column 108 and target water receiving flask 402 are sequentially communicated, the then valve in control system 113 and/or triple valve, so that booster pump 401 is connected to target water receiving flask 101, target water receiving flask 402 is connected to vacuum pump 111, The nitrogen that normal pressure is had finally by the conveying of booster pump 401 generates negative pressure by vacuum pump 111, so that target water Target water in receiving flask 101 can be by QMA column 108, so that in target water¹⁸F^-It is adsorbed on QMA column 108, and loses¹⁸F^-Afterwards Target water can smoothly enter and be stored in target water receiving flask 402, so as to it is convenient, be efficiently completed step 1；

For another example, in the step 2 provided by embodiment 1, it is desirable that utilize K222 and K₂CO₃Mixed solution by QMA column 108 On¹⁸F^-It elutes in reaction flask；Using this system, on the basis of step 1, controller can close device one by controlling folder 601, folder closes the closing of device 12, and controls folder and close device 2 602, press from both sides and close device 13, press from both sides to close device 15 and press from both sides and close device 16 open, so that No. 1 reagent bottle 102, QMA column 108 and reaction flask 109 are sequentially communicated, the then valve in control system Door 113 and/or triple valve generate negative pressure finally by vacuum pump 111 and (exist so that reaction flask 109 is connected to vacuum pump 111 Negative pressure is generated in reaction flask 109), to be contained in the K222 and K in No. 1 reagent bottle 102₂CO₃Mixed solution can pass through QMA column 108 realizes the elution to QMA column 108, and finally obtain elution¹⁸F^-It is transported in reaction flask 109, so as to Smoothly, it is efficiently completed step 2；Remaining step in synthesis technology is all gradually completing under the control of the controller, and final complete At¹⁸The synthesis of the red nitroimidazole of F- fluorine, will not enumerate here.

Above description is only a specific implementation of the present invention, but the protection scope of the utility model is not limited to In this, anyone skilled in the art within the technical scope disclosed by the utility model, can readily occur in variation Or replacement, it should be covered within the scope of the utility model.

Claims (10)

1. one kind is for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, which is characterized in that including target water receiving flask, No. 1 reagent bottle, 2 Number reagent bottle, No. 3 reagent bottles, No. 4 reagent bottles, No. 5 reagent bottles, cutting ferrule, QMA column, reaction flask, temperature controller one, vacuum pump, Half preparative high-performance liquid chromatographic instrument and controller, wherein

The target water receiving flask has for containing¹⁸F^-Target water, No. 1 reagent bottle is for containing K222 and K₂CO₃Mixing Solution, No. 2 reagent bottles are for containing anhydrous acetonitrile, and No. 3 reagent bottles are for containing precursor solution, No. 4 reagents Bottle is for containing hydrochloric acid, and No. 5 reagent bottles are for containing sodium hydroxide solution；

The cutting ferrule includes that pipe network and several folders close device, if the pipe network is made of trunk pipeline and several interfaces, the target water is received Collection bottle, No. 1 reagent bottle, No. 2 reagent bottles, No. 3 reagent bottles, No. 4 reagent bottles and No. 5 reagent bottles pass through pipeline and an institute respectively Interface is stated to be connected；

The both ends of the QMA column pass through pipeline respectively and are connected with two interfaces in the pipe network, and QMA column is used for acquisition target water In¹⁸F^-；

The reaction flask is connected by pipeline with an interface in the pipe network, and reaction flask is for being reacted；

The vacuum pump is connected by pipeline with an interface in the pipe network, and is connected with the controller, vacuum pump For generating negative pressure under the control of the controller, to carry out negative pressure transportation；

The sample injector of the half preparative high-performance liquid chromatographic instrument is connected by pipeline with an interface of the pipe network, and described half Preparative high-performance liquid chromatographic instrument is for isolating and purifying the product of collection；

The temperature controller one is set at the reaction flask, and is connected with the controller, for the control in controller The lower temperature for adjusting reaction flask；

Each folder closes device and is connected respectively with the controller, and the controller passes through controls each unlatching/pass for pressing from both sides and closing device respectively Close so that target water receiving flask, No. 1 reagent bottle, No. 2 reagent bottles, No. 3 reagent bottles, No. 4 reagent bottles and No. 5 reagent bottles with it is described Reaction flask is sequentially communicated/disconnects.

2. according to claim 1 for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, which is characterized in that the pipe network packet 13 pipelines and 16 interfaces are included, 13 pipelines are hose, wherein

Interface one is connected with interface nine by the first pipeline, and interface two is connected by the second pipeline with first pipeline, Interface eight is connected with interface 14 by third pipeline, and interface three is connected by the 4th pipeline with the third pipeline, is connect Mouth four is connected by the 5th pipeline with the 4th pipeline, and interface five is connected by the 6th pipeline with the 4th pipeline, Interface seven is connected by the 7th pipeline with the 4th pipeline, and interface six is connected by the 7th pipeline described in the 8th pipeline, Interface ten is connected by the 9th pipeline with first pipeline, and interface 12 is connected by the tenth pipeline with the interface 13 Logical, interface 11 is connected by the 11st pipeline with the tenth pipeline, and interface 15 passes through the 12nd pipeline and interface ten Six are connected, and the 13rd pipeline is connected with the 4th pipeline and the tenth pipeline respectively；Divide on the pipeline of each interface It is not provided with the folder and closes device；

The target water receiving flask is connected with the interface one, and No. 1 reagent bottle is connected with the interface two, and described No. 2 Reagent bottle is connected with the interface three, and No. 3 reagent bottles are connected with the interface four, No. 4 reagent bottles with it is described Interface six is connected, and No. 5 reagent bottles are connected with the interface seven；The half preparative high-performance liquid chromatographic instrument connects with described Mouthfuls eight are connected, and the QMA column is connected with the interface ten and interface 11 respectively, the interface 13, interface 14 with And interface 15 is connected with the reaction flask respectively, the interface five, interface nine and interface 16 respectively with the vacuum Pump is connected.

3. according to claim 2 for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, which is characterized in that the folder closes device For pinch valve.

4. according to claim 3 for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, which is characterized in that the folder closes device For electromagnetism pinch valve.

5. according to claim 2 for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, which is characterized in that further include outstanding steaming Bottle, No. 6 reagent bottles, filter and product receiving flask, wherein the outstanding steaming bottle passes through pipeline and the half preparation efficient liquid phase Chromatographic output end is connected, and the product receiving flask and No. 6 reagent bottles pass through pipeline respectively and are connected with the outstanding steaming bottle, described Filter is set on the outstanding pipeline steamed between bottle and product receiving flask, and No. 6 reagent bottles are used for containing physiological saline, filter In being filtered, and enter filtrate in the product receiving flask.

6. according to claim 2 for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, which is characterized in that further include No. 7 examinations Agent bottle and temperature controller two, No. 7 reagent bottles hang steaming bottle and half preparative high-performance liquid chromatographic instrument be connected to by triple valve Pipeline be connected, for containing ethyl alcohol, the triple valve is connected with the controller for No. 7 reagent bottles；The temperature controller Two are set at the outstanding steaming bottle, and are connected with the controller, for the outstanding steaming bottle of heating under the control of the controller.

7. according to claim 2 for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, which is characterized in that further include target water Returnable bottle, the target water returnable bottle are connected by pipeline with the interface 12, be used under the control of the controller with it is described QMA column is connected, and loses for collecting¹⁸F^-Target water afterwards.

8. according to claim 2 for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, which is characterized in that further include pressurization Pump, the booster pump pass through pipeline and the target water receiving flask, target water returnable bottle, No. 6 reagent bottles, No. 7 reagent bottles, outstanding steaming respectively Bottle, interface five, interface nine and interface 16 are connected, and booster pump is connected with the controller, and booster pump is used in controller Control under input have certain pressure nitrogen, so as to reagent carry out pressure conveying.

9. according to claim 2 for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, which is characterized in that further include radiation Property probe, the radio-metric probe is respectively arranged at the QMA column and the reaction flask, and respectively with the controller phase Even, the radio-metric probe at QMA column is set to for detecting in target water¹⁸F^-Whether all it is adsorbed on QMA column, is set to anti- Answer the radio-metric probe at bottle for detecting on QMA column¹⁸F^-All whether elution is into reaction flask.

10. according to claim 5 for synthesizing¹⁸The system of the red nitroimidazole of F- fluorine, which is characterized in that further include display Device and camera, the camera are respectively arranged at sample injector, the Yi Jisuo of the reaction flask, half preparative high-performance liquid chromatographic instrument State it is outstanding steam at bottle, the display and each camera are connected with the controller respectively, camera be respectively used to acquire reaction flask, Sample injector and the outstanding image information for steaming bottle, and shown using display.