WO2023236978A1

WO2023236978A1 - Device for producing liquid composition, preparation method therefor, and use thereof

Info

Publication number: WO2023236978A1
Application number: PCT/CN2023/098792
Authority: WO
Inventors: 王跃; 唐艳旻; 张颖; 张爱丽; 徐新盛
Original assignee: 北京先通国际医药科技股份有限公司
Priority date: 2022-06-07
Filing date: 2023-06-07
Publication date: 2023-12-14
Also published as: CN114700006B; CN114700006A; CN116351339A

Abstract

A device for producing a liquid composition of trans-2-[2-(5-[¹⁸F]fluorotridecyl)cyclopropyl]acetic acid (hereinafter referred to as "compound I"), comprising: a pretreatment module, configured to enrich ¹⁸F ions; a reaction module, configured to react the enriched ¹⁸F ions with a precursor of compound I to produce a tert-butyl ester of compound I, and perform a de-tert-butyl esterification reaction on the tert-butyl ester of compound I to obtain a crude product of compound I; a purification module, configured to purify the crude product of compound I to obtain a pure product of compound I; and a formulating module, configured to formulate the obtained pure product of compound I into the liquid composition of compound I. The device process operating flow described above is simple, the yield is high, and a single preparation can meet the needs of many users. The liquid composition of compound I is prepared for direct clinical use. Also provided are a method for preparing the liquid composition of compound I by using the aforementioned device, and a use of the aforementioned device in the preparation of the liquid composition of compound I.

Description

Production equipment for liquid composition and preparation method and use thereof

Technical field

The present application relates to the technical field of radiopharmaceuticals, and specifically to a production equipment for a liquid composition and its preparation method and use.

Background technique

According to data from a research report by the Chinese Center for Disease Control and Prevention, the proportion and absolute number of coronary heart disease deaths in the Chinese population have increased significantly. The total number of coronary heart disease deaths in China in 2013 was 1.394 million, an increase of 90% from the number of coronary heart disease deaths in 1990. %. Currently, coronary heart disease has become the leading cause of death in six provinces, municipalities/provincial administrative regions in my country. As the aging process intensifies, the number of incidences and deaths from coronary heart disease in my country will continue to increase.

With the development of clinical cardiology, the focus has gradually shifted from the original diagnosis of coronary artery disease to risk stratification and prognosis judgment. It is generally believed that information such as myocardial ischemia, cardiac function and viable myocardium can provide the main basis for coronary artery disease risk stratification, prognosis judgment and treatment plan formulation. Therefore, identifying viable myocardium has important clinical significance, and it is a hot topic in clinical treatment and prediction of related events. Currently, radionuclide myocardial imaging remains the gold standard for in vivo assessment of viable myocardium.

Trans-2-[2-(5-[ ¹⁸ F]fluorotridecyl)cyclopropyl]acetic acid (trans-2-[2-(5-[ ¹⁸ F]fluorotridecyl)cyclopropyl)acetic acid; hereinafter referred to as "Compound I") is a radionuclide ^18F -labeled modified fatty acid (MFA), which has a very similar structure to the naturally occurring free fatty acid (FFA) in the human body. It can be taken up by cardiomyocytes and used for positron-computed tomography imaging. Like (PET), evaluate the viability of cardiomyocytes. The structure of compound I is shown below:

Compound I can be imaged 5 minutes after intravenous injection, and has high compliance and clinical benefit.

The current equipment has many synthetic consumables, complex process operations, and low yield. A single preparation can only satisfy 1 to 2 people, and its clinical use is limited.

Therefore, it is particularly important to develop a device for producing liquid compositions of Compound I (such as injections).

Contents of the invention

In order to solve the problems in the prior art, this application provides equipment for producing compound I liquid compositions (such as injections) and preparation methods thereof. The technical solution for this application is as follows:

1. Equipment for producing compound I liquid composition, including:

Pretreatment module for enriching ¹⁸ F ions;

The reaction module is used to react the enriched ¹⁸ F ions with the precursor of Compound I to generate Compound I tert-butyl ester, and perform a de-tert-butyl esterification reaction on Compound I tert-butyl ester to obtain the crude compound I;

Purification module, used to purify crude compound I to obtain pure compound I;

The prescription module formulates the purified pure Compound I into a Compound I liquid composition;

2. The equipment described in item 1, the preprocessing module includes:

A first valve, a second valve, a third valve, a fourth valve, a fifth valve, and a sixth valve, the first valve to the sixth valve respectively include at least a first interface, a second interface, and a third interface, And the first valve to the sixth valve can realize any two of the three interfaces to be connected or all three interfaces to be disconnected; the first interface of the first valve and the first positive pressure pipe The second interface of the first valve is connected to the first interface of the second valve, the second interface of the second valve is connected to the first interface of the third valve, and the third valve The second interface of the fourth valve is connected to the first interface of the fourth valve, the second interface of the fourth valve is connected to the first interface of the fifth valve, and the second interface of the fifth valve is connected to the first interface of the fourth valve. The first interface of the six valves is connected;

The first recovery container is respectively connected to the first negative pressure pipeline and the third interface of the first valve;

The first reagent container is connected to the third interface of the second valve;

A first syringe connected to the third interface of the third valve;

¹⁸ F ion enrichment chamber, connected between the third interface of the fourth valve and the third interface of the fifth valve;

The second syringe is connected to the third interface of the sixth valve.

Preferably, the first valve, the second valve, the third valve, the fourth valve, the fifth valve and the sixth valve are all electric control valves.

3. The equipment described in item 2, the preprocessing module further includes:

A first linear drive device capable of driving the piston of the first syringe to move within the empty barrel;

A second linear drive device capable of driving the piston of the second syringe to move within the empty barrel.

Preferably, the first linear drive device and the second linear drive device are selected from one of a pneumatic rod, a hydraulic rod, and a screw;

Further preferably, both the first linear drive device and the second linear drive device are screws, and the screws are driven by stepper motors.

4. The device as described in item 2, the preprocessing module further includes:

Positive pressure and negative pressure pipelines and liquid adding pipelines respectively pass through the piston of the second syringe and extend into the second syringe.

Preferably, a flow meter is provided on the liquid adding pipeline.

5. The equipment as described in item 2, the reaction module includes:

The seventh valve, the eighth valve, the ninth valve, the tenth valve, the eleventh valve, the twelfth valve, and the thirteenth valve, the seventh valve to the thirteenth valve respectively include at least a first interface, The second interface, the third interface, and the seventh valve to the thirteenth valve can realize conduction of any two interfaces of the three interfaces or non-conduction of all three interfaces; the seventh valve The first interface is connected to the pretreatment module, the second interface of the seventh valve is connected to the first interface of the eighth valve, and the The second interface is connected to the first interface of the ninth valve, the second interface of the ninth valve is connected to the first interface of the tenth valve, and the second interface of the tenth valve is connected to the tenth valve. The first interface of a valve is connected to the first interface of the 11th valve. The second interface of the 12th valve is connected to the first interface of the 13th valve. One interface is connected, and the third interface of the twelfth valve is connected with the purification module;

The reaction vessel is respectively connected to the second negative pressure pipeline and the third interface of the seventh valve;

A temperature control component for heating and/or cooling the reaction vessel;

a second reagent container connected to the third interface of the eighth valve;

A third syringe connected to the third interface of the ninth valve;

A third reagent container is connected to the third interface of the tenth valve;

a fourth reagent container connected to the third interface of the eleventh valve;

The fifth reagent container is connected to the third interface of the thirteenth valve.

Preferably, the seventh valve, eighth valve, ninth valve, tenth valve, eleventh valve, twelfth valve and thirteenth valve are all electric control valves.

6. The equipment as described in item 5, the reaction module further includes:

A third linear drive device capable of driving the piston of the third syringe to move within the empty barrel.

Preferably, the third linear drive device is selected from one of a pneumatic rod, a hydraulic rod, and a screw;

Further preferably, the third linear driving device is a screw, and the screw is driven by a stepper motor.

7. The equipment as described in item 5, the purification module includes:

A fourteenth valve, the fourteenth valve includes at least a first interface, a second interface, a third interface, a fourth interface, a fifth interface, and a sixth interface, wherein the fourteenth valve can operate in the first mode and second mode, the first mode is that the first interface is connected to the second interface, the third interface is connected to the fourth interface, and the fifth interface is connected to the sixth interface; the second mode is The second interface is with The third interface is connected, the fourth interface is connected to the fifth interface, and the sixth interface is connected to the first interface; the fourth interface of the fourteenth valve is connected to the reaction module;

Chromatography column assembly, one end of the chromatography column assembly is connected to the second interface of the fourteenth valve;

A quantitative loop, both ends of which are respectively connected to the third interface of the fourteenth valve and the sixth interface of the fourteenth valve;

a liquid transfer pump, connected to the first interface of the fourteenth valve;

The second recovery container is connected to the fifth interface of the fourteenth valve;

The fifteenth valve includes at least a first interface, a second interface, and a third interface. The fifteenth valve can realize communication between the first interface and the second interface or the first interface and the third interface. conduction; the first interface of the fifteenth valve is connected to the other end of the chromatography column assembly, the second interface of the fifteenth valve is connected to the prescription module, and the first interface of the fifteenth valve is connected to the other end of the chromatography column assembly. Three interfaces are connected to the second recovery container;

Preferably, the fourteenth valve and the fifteenth valve are both electric control valves.

8. The device as described in item 7, the prescription module includes:

A sixteenth valve and a seventeenth valve, the sixteenth valve and the seventeenth valve respectively include at least a first interface, a second interface, and a third interface, and the sixteenth valve and the tenth valve Each of the seven valves can achieve conduction of any two of the three interfaces or non-conduction of all three interfaces; wherein, the first interface of the sixteenth valve is connected to the second interface of the thirteenth valve, The second interface of the sixteenth valve is connected to the first interface of the seventeenth valve, the third interface of the sixteenth valve is connected to the purification module, and the second interface of the seventeenth valve Connected to the third negative pressure pipeline;

Finished product collection containers;

The transfer container is respectively connected to the third interface of the seventeenth valve, the finished product collection container, and the fourth negative pressure pipeline.

9. A method for producing a liquid composition of Compound I, using the equipment described in any one of items 1 to 8, including:

Use the preprocessing module to enrich ¹⁸ F ions;

Use the reaction module to react the enriched ¹⁸ F ions with the precursor of compound I to generate compound I tert-butyl ester, and perform a de-tert-butyl esterification reaction on compound I tert-butyl ester to obtain compound I crude product;

Use the purification module to purify the crude compound I to obtain the pure compound I;

Use the formulation module to formulate the purified pure compound I into a compound I liquid composition.

10. Use of the equipment described in any one of items 1 to 8 in producing compound I liquid composition.

The equipment provided by this application for producing a compound I liquid composition can prepare a crude compound I, and the crude compound I is purified and formulated to prepare a compound I liquid composition for direct clinical use, and its process operation flow It is simple, has high yield, and can be used by many people in a single preparation. Moreover, each valve can be controlled through a microprocessor control system (such as PLC, etc.) to realize equipment automation. At the same time, this application provides methods for using the above equipment.

The above description is only an overview of the technical solutions of the present application. In order to make the technical means of the present application more clear and understandable to the extent that those skilled in the art can implement them according to the contents of the description, and in order to achieve the above and other purposes of the present application, The features and advantages can be more clearly understood and are illustrated below with specific embodiments of the present application.

Description of the drawings

Figure 1: Schematic assembly diagram of the pretreatment module, reaction module, and formulation module of the equipment for producing compound I;

Figure 2(a) ~ Figure 2(b): Schematic diagram of the purification module of the equipment for producing compound I (the purification module performs purification by switching between the mode of Figure 2(a) and the mode of Figure 2(b));

Figure 3(a) ~ Figure 3(h): Schematic diagram of the three-way valve structure (Figure 3(a) is a schematic diagram of the three interfaces in the three-way valve being connected; Figure 3(b) ~ Figure 3(d) are the three Schematic diagram of the two interfaces in the one-way valve being connected; Figure 3(e) to Figure 3(h) are respectively schematic diagrams of the three interfaces of the three-way valve being disconnected);

Figure 4(a) ~ Figure 4(d): A simplified diagram of the three-way valve in Figure 3(a) ~ Figure 3(h) (Figure 4(a) is a simplified diagram corresponding to the three-way valve in Figure 3(b); Figure 4(b) is a simplified diagram corresponding to the three-way valve in Figure 3(c); Figure 4(c) is a simplified diagram corresponding to the three-way valve in Figure 3(d) Figure; Figure 4(d) is a simplified diagram of the three-way valve corresponding to Figure 3(e) to Figure 3(h));

Figure 5(a) ~ Figure 5(b): Schematic diagram of the six-way valve structure (Figure 5(a) and Figure 5(b) are schematic diagrams of the six-way valve core in different working positions respectively);

Figure 6(a) ~ Figure 6(c): Schematic diagram of the working principle of the pretreatment module (the pretreatment module implements ¹⁸ F ion enrichment and sends it to the reaction module in the order of Figure 6(a) ~ Figure 6(c));

Figure 7(a) ~ Figure 7(h): Schematic diagram of the working principle of the reaction module (the reaction module is in accordance with Figures 7(a), 7(b), 7(c), 7(d), 7(e), 7(d) ), 7(b), 7(f), 7(d), 7(g), 7(d), 7(h) are reacted in sequence);

Figure 8(a) ~ Figure 8(b): Schematic diagram of the working principle of the prescription module (the prescription module performs prescription and collects the final product in the order of Figures 8(a) and 8(b));

Figure 9: Schematic diagram of total negative pressure pipeline connection.

Explanation of reference symbols:

1～17, the first valve to the seventeenth valve; V1, three-way valve body; V2, three-way valve core; V3, six-way valve body; V4, six-way valve core;

18. The first recovery container; 19. The first reagent container; 20. The first syringe; 21. ¹⁸ F ion enrichment chamber; 22. The second syringe; 23. Positive pressure and negative pressure pipeline; 24. Liquid addition pipeline ;

25. Reaction container; 26. Second reagent container; 27. Third syringe; 28. Third reagent container; 29. Fourth reagent container; 30. Fifth reagent container;

31. Chromatographic column assembly; 32. Quantitative loop; 33. Liquid transfer pump; 34. Second recovery container;

35. Transfer container; 36. Finished product collection container;

37. The third recycling container;

P0, the positive pressure pipeline of the positive pressure and negative pressure pipeline; P1, the first positive pressure pipeline;

N, total negative pressure pipeline; N0, negative pressure pipeline of positive pressure and negative pressure pipeline; N1, first negative pressure pipeline; N2, second negative pressure pipeline; N3, third negative pressure pipeline; N4 , the fourth negative pressure pipeline.

Detailed ways

The following embodiments of the present application are only used to illustrate specific implementation methods for implementing the present application, and these embodiments cannot be understood as limitations of the present application. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of this application will be regarded as equivalent substitutions and fall within the protection scope of this application.

This embodiment provides a method for producing trans-2-[2-(5-[ ^18F ]fluorotridecyl)cyclopropyl]acetic acid

(hereinafter referred to as "Compound I") liquid composition (such as injection) equipment, including:

Pretreatment module for enriching ¹⁸ F ions;

The reaction module is used to react the enriched ¹⁸ F ions with the precursor of compound I to generate compound I tert-butyl ester, and perform the de-tert-butyl esterification reaction of compound I tert-butyl ester to obtain compound I crude product;

Purification module, used to purify crude compound I to obtain pure compound I;

The prescription module formulates the purified pure Compound I into a Compound I liquid composition.

As shown in the figure below, compound I is prepared through a two-step reaction using compound I precursor and radioactive fluorine [ ^18F ] ions as starting materials. The first step is to nucleophilically substitute the methanesulfonyloxy group (-OMs) in the precursor of compound I with fluorine [ ¹⁸ F] to obtain the tert-butyl ester of compound I. In the second step, trifluoroacetic acid/acetonitrile solution is added without separation and purification to perform de-tert-butyl esterification reaction to obtain crude compound I. The synthetic route of crude compound I is shown in the figure below.

In the figure, K ₂₂₂ is 4,7,13,16,21,24-hexoxo-1,10-diazabicyclo[8.8.8]hexadecane, referred to as aminopolyether.

Therefore, it can be known that the process for preparing crude compound I in this application is different from that in the applicant's other application. Therefore, the applicant made corresponding improvements to the production equipment, resulting in this application.

This embodiment provides a device for producing compound I liquid composition (such as injection), which first enriches ¹⁸ F ions through the pretreatment module; the enriched ¹⁸ F ions enter the reaction module, and then in the reaction module React with the precursor of Compound I to generate Compound I tert-butyl ester, and further perform a de-tert-butyl esterification reaction on Compound I tert-butyl ester to obtain Compound I crude product; Compound I crude product enters the purification module for purification, thereby obtaining Compound I pure product; Further, the pure compound I enters the prescription module and is formulated into a liquid composition of compound I.

Through the technical solution of this embodiment, the crude compound I can be obtained, and the crude compound I is purified and formulated for direct clinical use.

In addition, it should be noted that the "crude product" and "pure product" in this application refer to the products before and after purification respectively; the "formulation" in this example specifically refers to formulating the pure product of Compound I with auxiliary materials into Compound I Liquid composition.

In one embodiment, the preprocessing module shown in Figure 1, Figure 3(a)-Figure 3(h), Figure 4(a)-Figure 4(d), and Figure 6(a)-Figure 6(c) include:

The first valve 1 , the second valve 2 , the third valve 3 , the fourth valve 4 , the fifth valve 5 , and the sixth valve 6 respectively include at least a first interface, a second interface, and a second valve 6 . interface, the third interface, and the first valve 1 to the sixth valve 6 can realize conduction of any two interfaces of the three interfaces or non-conduction of all three interfaces; the first valve of the first valve 1 The interface is connected to the first positive pressure pipeline P1, the second interface of the first valve 1 is connected to the first interface of the second valve 2, and the second interface of the second valve 2 is connected to the third valve 3 is connected to the first interface, the second interface of the third valve 3 is connected to the first interface of the fourth valve 4, the second interface of the fourth valve 4 is connected to the first interface of the fifth valve 5 The interfaces are connected, and the second interface of the fifth valve 5 is connected to the first interface of the sixth valve 6;

The first recovery container 18 is respectively connected to the first negative pressure pipeline N1 and the third interface of the first valve 1;

The first reagent container 19 is connected to the third interface of the second valve 2. The first reagent container 19 is used to hold ¹⁸ F eluent (such as: acetonitrile + water + K ₂₂₂ + K ₂ CO ₃ , etc. );

The first syringe 20 is connected to the third interface of the third valve 3;

¹⁸ F ion enrichment chamber 21 is connected between the third interface of the fourth valve 4 and the third interface of the fifth valve 5, and the ¹⁸ F ion enrichment chamber 21 is filled with anion exchange resin;

The second syringe 22 is connected to the third interface of the sixth valve 6;

Preferably, the first valve 1, the second valve 2, the third valve 3, the fourth valve 4, the fifth valve 5 and the sixth valve 6 are all electric control valves (such as solenoid valves).

First, as shown in Figure 3 (a) to Figure 3 (h), a three-way valve is provided, which can realize the functions of the first valve 1 to the sixth valve 6 mentioned above. Of course, it can also realize the seventh valve below. The functions of the valves 7 to 13, the 16th valve 16, and the 17th valve 17 will not be described again below.

As shown specifically in Figures 3(a) to 3(h), the three-way valve includes a three-way valve core V2 with a circular cross-section, and a three-way valve body V1 outside the three-way valve core V2. The one-way valve body V1 is provided with a first interface ① on the left side, a second interface ② on the right side, and a third interface ③ on the upper side. A T-shaped flow channel is provided in the three-way valve core V2. By rotating the valve core V2, the first interface ① and the third interface ③ can be connected (as shown in Figure 3(b)), the first interface ① can be connected with the second interface ② (as shown in Figure 3(c)), and the first interface ① can be connected with the second interface ② (as shown in Figure 3(c)). The second interface ② is connected to the third interface ③ (as shown in Figure 3(d)), and the three interfaces are not connected (as shown in Figure 3(e) to Figure 3(h)). In addition, based on the above three-way valve structure, those skilled in the art know based on the existing technology how to control the three-way valve core V2 to rotate at a fixed angle relative to the three-way valve body V1 to realize the electric operation of the three-way valve ( Electromagnetic) control (for example, setting a stepper motor to control the rotation of the three-way valve spool V2). In addition, in order to simply describe the state of the three-way valve in the following, Figures 4(a) to 4(d) provide schematic diagrams of the three-way valve in Figures 3(a) to 3(h), where, Figure 4(a) is a simplified diagram corresponding to the three-way valve in Figure 3(b); Figure 4(b) is a simplified diagram corresponding to the three-way valve in Figure 3(c); Figure 4(c) is corresponding to Figure 3(d) A schematic diagram of a three-way valve; Figure 4(d) is a schematic diagram of the three-way valve corresponding to Figures 3(e) to 3(h).

In addition, the first negative pressure pipeline N1 specifically provides negative pressure through vacuuming. The negative pressure pipeline N0, the second negative pressure pipeline N2, and the third negative pressure pipeline N3 of the positive pressure and negative pressure pipelines below are The fourth negative pressure pipeline N4 can also provide negative pressure through vacuuming, which will not be described again below. And, positive pressure and negative pressure The negative pressure pipeline N0, the first negative pressure pipeline N1, the second negative pressure pipeline N2, the third negative pressure pipeline N3, and the fourth negative pressure pipeline N4 of the pipeline can be connected to a vacuum equipment separately, or they can Two or more of them are connected to a vacuum equipment/pipeline. Specifically, as shown in FIG. 9 , the third recovery container 37 is connected to the total negative pressure pipeline N, and the other negative pressure pipelines (the negative pressure pipeline N0 of the positive pressure and negative pressure pipeline, the first negative pressure pipeline N1 , more than one of the second negative pressure pipeline N2, the third negative pressure pipeline N3, and the fourth negative pressure pipeline N4) is also connected to the third recovery container 37 (specifically, the left side of the third recovery container 37 in Figure 9 pipeline connection), so that more than one negative pressure pipeline can be driven to work through a vacuuming device, and the third recovery container 37 can store the liquid flowing in from the negative pressure pipeline.

The first positive pressure pipeline P1 provides positive pressure by blowing out inert gases (such as nitrogen, argon, etc.). In addition, a filter membrane can be installed in the first positive pressure pipeline P1 to ensure the cleanliness of the inert gas entering the equipment. The positive pressure pipeline P0 of the positive pressure and negative pressure pipeline below can also provide positive pressure in this way, which will not be described again below.

Moreover, those skilled in the art know that generally, the negative pressure pipeline N0 of the positive pressure and negative pressure pipeline, the first negative pressure pipeline N1, the second negative pressure pipeline N2, the third negative pressure pipeline N3, A control valve (such as an electric control valve, specifically a solenoid valve) is provided on the fourth negative pressure pipeline N4, the positive pressure pipeline P0 of the positive pressure and negative pressure pipeline, and the first positive pressure pipeline P1 to control the opening and closing of the pipelines. , and/or set up a flow valve/flow meter to control the positive pressure/negative pressure, etc., which will not be described again in this article.

Those skilled in the art know that an empty cylinder and a piston within the empty cylinder are necessary components of a syringe. The piston can be a long strip structure, and the piston can move relative to the empty cylinder by pushing the part of the piston outside the empty cylinder; the piston can also be just a rubber head that has a sealing function and is located inside the empty cylinder. At this time, the piston is A core rod will be installed, and the core rod can be pushed to drive the relative movement of the piston and the empty cylinder. As shown in Figure 1, the structure of the syringe is composed of a hollow cylinder, a piston and a core rod.

The specific process of enriching ¹⁸ F ions by the pretreatment module can be shown in Figure 6(a) to Figure 6(c).

Initially, the states of the first to sixth valves 1 to 6 are as shown in Figure 6(a). At this time, the first negative pressure pipeline N1 is evacuated. Then the second syringe 22 pushes out the oxygen [ ¹⁸ O]octahydrate containing ¹⁸ F ions, When the oxygen [ ¹⁸ O]octahydrate containing ¹⁸ F ions flows through the 18 F ion enrichment chamber 21, ^{the 18} ^F ions are enriched in the ¹⁸ F ion enrichment chamber 21, and the remaining liquid flows into the first recovery container 18;

After that, the states of the second valve 2 to the third valve 3 are as shown in Figure 6(b), and the first syringe 20 draws in the ¹⁸ F eluent in the first reagent container 19;

Finally, the states of the third to sixth valves 3 to 6 are as shown in Figure 6(c). The first syringe 20 pushes out the ^18F eluent, and the ^18F eluent will be enriched in the ^18F ion enrichment chamber. The ¹⁸ F ions in the reaction module are fed into the reaction module.

This embodiment provides a specific pretreatment module that can simply and conveniently enrich ¹⁸ F ions and elute the enriched ¹⁸ F ions and send them to the subsequent reaction module. Especially when each valve, positive pressure pipeline, negative pressure pipeline, and injector are automatically controlled, automatic processing of ¹⁸ F ion enrichment, elution, and delivery to the reaction module can be realized.

In one embodiment, the preprocessing module also includes:

A first linear drive device (not shown in the drawings), the first linear drive device can drive the piston of the first syringe 20 to move within the empty barrel;

a second linear drive device (not shown in the drawings), the second linear drive device can drive the piston of the second syringe 22 to move within the empty barrel;

In this embodiment, the first linear drive device and the second linear drive device are provided to control the first syringe 20 and the second syringe 22 .

When using a pneumatic rod or a hydraulic rod in conjunction with a controller such as a PLC, it is convenient to realize automatic control of the first syringe 20 and the second syringe 22.

Using the screw, the movement of the pistons in the first syringe 20 and the second syringe 22 can be accurately controlled. process, especially when the screw is driven by a stepper motor, it is convenient to cooperate with a microprocessor control system (PLC, etc.) to realize automatic and precise control of the first syringe 20 and the second syringe 22. The screw driven by the stepper motor can be assembled by yourself, or you can directly purchase the finished electric actuator (a screw system).

In one embodiment, as shown in Figure 1, the pretreatment module also includes a positive pressure and negative pressure pipeline 23 and a liquid adding pipeline 24. The positive pressure and negative pressure pipeline 23 and the liquid adding pipeline 24 respectively pass through the first The piston of the second syringe 22 extends into the closed space formed by the piston of the second syringe 22 and the empty cylinder;

Preferably, the liquid adding pipeline 24 is provided with a flow meter, so that the amount of liquid added can be controlled, and/or the liquid adding pipeline 24 is provided with a control valve (such as an electric control valve, specifically a solenoid valve), The control valve can control the opening and closing of the pipeline, thereby controlling whether to add liquid.

In this application, the positive pressure and negative pressure pipeline 23 is a positive pressure pipeline P0 of the positive pressure and negative pressure pipeline, and a negative pressure pipeline N0 of the positive pressure and negative pressure pipeline connected to one pipeline. Pass through the piston (as shown in Figure 1); or, the positive pressure pipeline P0 of the positive pressure and negative pressure pipeline, and the negative pressure pipeline N0 of the positive pressure and negative pressure pipeline pass through the piston respectively.

Then, the present application provides a solution for adding liquid (oxygen [ ¹⁸ O]octahydrate containing ¹⁸ F ions) to the second syringe 22. Specifically, the liquid is added through the liquid adding line. At the same time, in order to prevent the second The pressure in the syringe 22 is too high, and the negative pressure pipeline N0 of the positive pressure and negative pressure pipeline is evacuated to achieve liquid addition. After adding liquid, the liquid in the second syringe 22 can be discharged for subsequent processing by pushing the piston downward/pushing out the inert gas (pressurization) through the positive pressure pipeline P0 of the positive pressure and negative pressure pipeline.

This embodiment provides a solution for adding liquid to the second syringe 22 . This can provide more oxygen [ ^18O ]octahydrate containing ^18F ions for ^18F ion enrichment, and provide more ^18F ions continuously for subsequent reactions. And it can provide positive pressure through the positive pressure pipeline P0 of the positive pressure and negative pressure pipeline to add liquid to the subsequent process, or push the piston to more accurately add liquid to the subsequent process.

In one embodiment, as shown in Figure 1, the reaction module includes:

The seventh valve 7, the eighth valve 8, the ninth valve 9, the tenth valve 10, the eleventh valve 11, the twelfth valve 12, the thirteenth valve 13, the seventh valve 7 to the thirteenth valve The valves 13 respectively include at least a first interface, a second interface, and a third interface, and the seventh valve 7 to the thirteenth valve 13 can realize any two interfaces among the three interfaces to be connected or make the three interfaces conductive. None of them are conductive; the first interface of the seventh valve 7 is connected to the pretreatment module (the second interface of the sixth valve 6), and the second interface of the seventh valve 7 is connected to the eighth The first interface of the valve 8 is connected, the second interface of the eighth valve 8 is connected with the first interface of the ninth valve 9, the second interface of the ninth valve 9 is connected with the third interface of the tenth valve 10 One interface is connected, the second interface of the tenth valve 10 is connected with the first interface of the eleventh valve 11 , the second interface of the eleventh valve 11 is connected with the first interface of the twelfth valve 12 The second interface of the twelfth valve 12 is connected to the first interface of the thirteenth valve 13, and the third interface of the twelfth valve 12 is connected to the purification module (the fourteenth The fourth interface of the valve 14) is connected;

The reaction vessel 25 is connected to the second negative pressure pipeline N2 and the third interface of the seventh valve 7 respectively. Preferably, the second negative pressure pipeline N2, the reaction vessel 25 and the seventh valve 7 are connected to each other. The pipelines between the third interfaces of 7 are equipped with control valves (such as electric control valves, specifically solenoid valves), which can control the on-off of the pipeline, thereby ensuring that the reaction proceeds in the reaction vessel 25;

A temperature control component (not shown in the drawings) is used to heat and/or cool the reaction vessel 25. The heating can be done by electric heating, and the cooling can be done by air cooling. Specifically, it can be done with reference to the existing technology. I won’t go into details here;

The second reagent container 26 is connected to the third interface of the eighth valve 8. The second reagent container 26 is used to hold the compound I precursor acetonitrile solution;

The third syringe 27 is connected to the third interface of the ninth valve 9;

The third reagent container 28 is connected to the third interface of the tenth valve 10. The third reagent container 28 is used to hold TFA/ACN (trifluoroacetic acid/acetonitrile) solution;

The fourth reagent container 29 is connected to the third interface of the eleventh valve 11. The fourth reagent container 29 is connected to the third interface of the eleventh valve 11. Container 29 is used to hold water (sterile water for injection);

The fifth reagent container 30 is connected to the third interface of the thirteenth valve 13, and the fifth reagent container 30 is used to hold absolute ethanol;

Preferably, the seventh valve 7 , the eighth valve 8 , the ninth valve 9 , the tenth valve 10 , the eleventh valve 11 , the twelfth valve 12 , and the thirteenth valve 13 are all electric control valves (such as electromagnetic valves). valve).

The structures of the seventh valve 7 to the thirteenth valve 13, the third syringe 27, etc. in this embodiment have been introduced above and will not be described again here.

The specific reaction process of the reaction module is shown in Figure 7(a) to Figure 7(h).

Initially, the state of the seventh valve 7 is as shown in Figure 7(a). At this time, the enriched ¹⁸ F ions are sent by the pretreatment module into the reaction vessel 25 (specifically, it can be a reaction bottle) through the seventh valve 7.

Afterwards, the states of the first to seventh valves 1 to 7 are as shown in Figure 7(b). At this time, the first positive pressure pipeline P1 outputs positive pressure (inputs inert gas) and the second negative pressure to the reaction vessel 25. The pipeline N2 is evacuated, and the temperature control component heats the reaction vessel 25 to remove the solvent. The heating temperature at this time is 80 to 130°C, so that activated ¹⁸ F ions can be obtained.

Afterwards, the states of the eighth to ninth valves 8 to 9 are as shown in Figure 7(c), and the third syringe 27 draws out the compound I precursor acetonitrile solution in the second reagent container 26;

Afterwards, the states of the seventh to ninth valves 7 to 9 are as shown in Figure 7(d). The third syringe 27 takes out the extracted acetonitrile solution of the compound I precursor (0.2 acetonitrile solution containing 1 to 10 mg of the compound I precursor). -2.0ml) into the reaction vessel 25; the temperature control component is heated, heated to 90-140°C under closed conditions and reacted for 2-20 minutes. The precursor of compound I undergoes a nucleophilic substitution reaction with K ¹⁸ F/K ₂₂₂ to generate compound I. tert-butyl ester;

Afterwards, the states of the ninth valve 9 to the tenth valve 10 are as shown in Figure 7(e), and the third syringe 27 draws out the TFA/ACN solution contained in the third reagent container 28;

After that, the states of the seventh to ninth valves 7 to 9 are as shown in Figure 7(d), and the third syringe 27 injects the extracted TFA/ACN solution (0.2 to 2.0 ml of 10 to 50% TFA/ACN solution). into the reaction vessel 25; the temperature control component is heated, and the substances react in the reaction vessel 25, React at 30-100°C for 1-30 minutes to remove the tert-butyl ester protecting group;

Afterwards, after the reaction is cooled, the states of the first to seventh valves 1 to 7 are as shown in Figure 7(b). The first positive pressure pipeline P1 outputs positive pressure and the second negative pressure pipeline N2 to the reaction vessel 25. Perform vacuuming, and the temperature control component heats the reaction vessel 25 to remove TFA/ACN;

After that, the states of the ninth valve 9 to the eleventh valve 11 are as shown in Figure 7(f), and the third syringe 27 draws the water contained in the fourth reagent container 29;

After that, the states of the seventh valve 7 to the ninth valve 9 are as shown in Figure 7(d), and the third syringe 27 pushes the extracted water into the reaction container 25;

Afterwards, the states of the ninth valve 9 to the eleventh valve 13 are as shown in Figure 7(g), and the third syringe 27 draws out the absolute ethanol contained in the fifth reagent container 30;

Afterwards, the states of the seventh valve 7 to the ninth valve 9 are as shown in Figure 7(d), and the third syringe 27 pushes the extracted absolute ethanol into the reaction vessel 25;

After that, the states of the seventh valve 7 to the ninth valve 9 are still as shown in Figure 7(d), and the third syringe 27 extracts the liquid in the reaction container 25;

Finally, the states of the ninth to twelfth valves 9 to 12 are as shown in FIG. 7(h) , and the third syringe 27 pushes the extracted liquid in the reaction vessel 25 into the purification module.

This embodiment provides a specific reaction module, by changing the changes of the seventh valve 7 to the thirteenth valve 13 in different working states, as well as the first positive pressure pipeline P1, the second negative pressure pipeline N2 and the reaction module. The container 25 and the temperature control component work together to skillfully realize the nucleophilic substitution reaction between the precursor of compound I and K ¹⁸ F/K ₂₂₂ to generate the tert-butyl ester of compound I and the removal of tert-butyl ester of compound I through simple equipment. Esterification reaction. Especially when each valve, positive pressure pipeline, negative pressure pipeline, and syringe are automatically controlled, the automation of the above two-step reaction can be realized.

In one embodiment, the reaction module further includes:

A third linear drive device (not shown in the drawings), the third linear drive device can drive the piston of the third syringe 27 to move within the empty barrel;

In this embodiment, a third linear drive device is provided to control the third syringe 27 .

When a pneumatic rod or a hydraulic rod is used in conjunction with a PLC or other controller, automatic control of the third syringe 27 can be easily realized.

Using the screw, the stroke of the piston in the third syringe 27 can be accurately controlled. Especially when the screw is driven by a stepper motor, it is convenient to cooperate with a microprocessor control system (PLC, etc.) to achieve automatic and precise control of the third syringe 27 . The screw driven by the stepper motor can be assembled by yourself, or you can directly purchase the finished electric actuator (a screw system).

In one embodiment, as shown in Figure 2(a) to Figure 2(b), the purification module includes:

The fourteenth valve 14 includes at least a first interface, a second interface, a third interface, a fourth interface, a fifth interface, and a sixth interface (corresponding to Figures 5(a) to 5( respectively). ①～⑥) in b), wherein the fourteenth valve 14 can switch between a first mode and a second mode. The first mode is for the first interface to be connected to the second interface and the third interface to be connected. The fourth interface is connected to the fourth interface, and the fifth interface is connected to the sixth interface. The second mode is that the second interface is connected to the third interface, the fourth interface is connected to the fifth interface, and the sixth interface is connected to the first interface. Conductive; the fourth interface of the fourteenth valve 14 is connected to the reaction module (the third interface of the twelfth valve 12) (pipe A is connected to pipe A');

Chromatography column assembly 31, one end of the chromatography column assembly 31 is connected to the second interface of the fourteenth valve 14;

Quantitative loop 32 (also called injection loop), both ends of the quantitative loop 32 are connected to the third interface of the fourteenth valve 14 and the sixth interface of the fourteenth valve 14 respectively;

The liquid delivery pump 33 is connected to the first interface of the fourteenth valve 14 and is used to deliver fluid. (The solution of ethanol and water, the ratio is: ethanol/water=5/1~2/1);

The second recovery container 34 is connected to the fifth interface of the fourteenth valve 14;

The fifteenth valve 15 includes at least a first interface, a second interface, and a third interface. The fifteenth valve 15 can realize communication between the first interface and the second interface or the connection between the first interface and the second interface. The third interface is conductive; the first interface of the fifteenth valve 15 is connected to the other end of the chromatography column assembly 31, and the second interface of the fifteenth valve 15 is connected to the prescription module (sixteenth The third interface of the valve 16 is connected to the third interface of the fifteenth valve 15, and the third interface of the fifteenth valve 15 is connected to the second recovery container 34;

Preferably, the fourteenth valve 14 and the fifteenth valve 15 are both electric control valves.

First, as shown in Figures 5(a) to 5(b), a six-way valve is provided, which can realize the function of the fourteenth valve 14 mentioned above.

As specifically shown in Figures 5(a) to 5(b), the six-way valve includes a six-way valve core V4 with a circular cross-section, and a six-way valve body V3 outside the six-way valve core V4. The valve body V3 is respectively provided with a first interface ①, a second interface ②, a third interface ③, a fourth interface ④, a fifth interface ⑤, and a sixth interface ⑥ in the counterclockwise direction. By rotating the valve core V4, the first interface ① is connected to the second interface ②, the third interface ③ is connected to the fourth interface ④, and the fifth interface ⑤ is connected to the sixth interface ⑥ (as shown in Figure 5(a)), or The second interface ② is connected to the third interface ③, the fourth interface ④ is connected to the fifth interface ⑤, and the sixth interface ⑥ is connected to the first interface ① (as shown in Figure 5(b)). In addition, based on the above-mentioned six-way valve structure, those skilled in the art know based on the existing technology how to control the six-way valve core V4 to rotate at a fixed angle relative to the six-way valve body V3 to realize the electric operation of the six-way valve ( Electromagnetic) control (for example, setting a stepper motor to control the rotation of the spool V4).

In addition, as shown in Figure 2(a) and Figure 2(b), the fifteenth valve 15 is a three-way valve, which can realize the connection between the first interface ① and the second interface ② or the first interface ① It is connected to the third interface ③, which is an existing technology, and the corresponding electric control valve (such as a solenoid valve) can be purchased directly on the market.

The chromatographic column is an existing technology and will not be described in detail here. The chromatography column assembly 31 of the present application is an existing chromatography column or a combination of multiple chromatography columns (such as a series and/or parallel connection of multiple chromatography columns).

The specific process of purification by the purification module can be shown in Figure 2(a) and Figure 2(b).

Initially, the state of the fourteenth valve 14 is as shown in Figure 2(a). At this time, the solution flowing in from the reaction module to dissolve the crude compound I enters the quantitative loop 32 through the fourth interface ④ and the third interface ③, and a small amount is excess. The solution flows into the second recovery container 34 through the sixth interface ⑥ and the fifth interface ⑤. At this time, the solution in which the crude compound I is dissolved will remain in the quantitative loop 32.

After that, the state of the fourteenth valve 14 is as shown in Figure 2(b). The fifteenth valve 15 connects the first interface ① and the third interface ③. At this time, the liquid transfer pump 33 starts to work. The liquid transfer pump 33 pushes out the fluid (ethanol and water). After the fluid flows through the first interface ① and the sixth interface ⑥, the solution of the crude compound I dissolved in the quantitative loop 32 is taken out and passes through the third interface ③ and the sixth interface. The second interface ② flows into the chromatographic column assembly 31 to perform purification.

Finally, the fifteenth valve 15 connects the first interface ① and the second interface ②, and the fluid pushed out by the liquid delivery pump 33 pushes the purified compound I product solution into the prescription module.

This embodiment provides a specific purification module. By changing the changes of the fourteenth valve 14 and the fifteenth valve 15 in different working states and cooperating with the liquid transfer pump 33, the crude compound I can be purified to obtain Compound Ⅰ pure product. Especially when each valve and the liquid transfer pump 33 are automatically controlled, the above-mentioned purification can be automated.

In one embodiment, the prescription module includes:

The sixteenth valve 16 and the seventeenth valve 17 respectively include at least a first interface, a second interface and a third interface, and the sixteenth valve and The seventeenth valve can achieve any two interfaces among the three interfaces to be connected or all three interfaces to be disconnected; wherein, the first interface of the sixteenth valve 16 and the thirteenth valve 13 The second interface of the sixteenth valve 16 is connected to the first interface of the seventeenth valve 17, and the third interface of the sixteenth valve 16 is connected to the purification module (tenth The second interface of the fifth valve 15 is connected (pipeline B is connected to pipe B'), and the second interface of the seventeenth valve 17 is connected to the third negative pressure pipe N3;

The finished product collection container 36 is connected to the transfer container 35;

The transfer container 35 is respectively connected to the third interface of the seventeenth valve 17, the finished product collection container 36, and the fourth negative pressure pipeline N4. The transfer container 35 contains polysorbate 80 (Ⅱ), chlorine Sodium chloride, vitamin C and sterile water for injection are used for prescription preparation.

The structures of the sixteenth valve 16 and the seventeenth valve 17 in this embodiment have been introduced above and will not be described again here.

The specific process of enrichment and prescription by the prescription module is shown in Figure 8(a) to Figure 8(b).

Initially, the states of the sixteenth valve 16 and the seventeenth valve 17 are as shown in Figure 8(a). At this time, the compound I product solution flowing out from the purification module enters the transfer container 35 to be formulated;

After that, the states of the first valve 1 to the seventeenth valve 17 are as shown in Figure 8(b), the first positive pressure pipeline P1 is supplied with positive pressure, and the formulated compound I solution is pushed into the finished product collection container 36. Thus, a liquid composition of Compound I was collected. Preferably, a filter (such as a needle filter) is provided between the transfer container 35 and the finished product collection container 36 to filter and sterilize the compound I solution flowing out of the transfer container 35 to obtain the final product.

This embodiment provides a specific prescription module. By controlling the sixteenth valve 16 and the seventeenth valve 17 and working in conjunction with the purification module, the purified compound I is formulated and further collected to obtain Compound I liquid composition. Especially when the sixteenth valve 16, the seventeenth valve 17, etc. are automatically controlled, the automation of the above-mentioned prescription and collection can be realized.

In addition, in the above technical solution, detection/monitoring equipment is set up to detect the operation of the equipment. Specifically, the radioactivity detector may be provided at one position or at more than two positions in the pipeline between the ¹⁸ F ion enrichment chamber 21, the fifth reagent container 30, the twelfth valve 12 and the fourteenth valve 14. to detect radioactivity. UV detectors and radioactive detectors can be set on the column assembly to determine whether the control starts to collect the purification mobile phase.

This embodiment provides a method for producing a liquid composition of Compound I using the above-mentioned equipment. laws, including:

Use the preprocessing module to enrich ¹⁸ F ions;

More specific operation steps have been introduced above and will not be described again.

Although the embodiments of the present application have been described above, the present application is not limited to the above-mentioned specific embodiments and application fields. The above-mentioned specific embodiments are only illustrative and instructive, rather than restrictive. Under the inspiration of this description and without departing from the scope of protection of the claims of this application, those of ordinary skill in the art can also make many forms, which all fall within the scope of protection claimed by this application.

Claims

Equipment for producing compound I liquid compositions, including:

Pretreatment module for enriching 18 F ions;

The reaction module is used to react the enriched 18 F ions with the precursor of Compound I to generate Compound I tert-butyl ester, and perform a de-tert-butyl esterification reaction on Compound I tert-butyl ester to obtain the crude compound I;

Purification module, used to purify crude compound I to obtain pure compound I;

The prescription module formulates the purified pure Compound I into a Compound I liquid composition;
The device of claim 1, wherein,

The preprocessing module includes:

A first valve, a second valve, a third valve, a fourth valve, a fifth valve, and a sixth valve, the first valve to the sixth valve respectively include at least a first interface, a second interface, and a third interface, And the first valve to the sixth valve can realize any two of the three interfaces to be connected or all three interfaces to be disconnected; the first interface of the first valve and the first positive pressure pipe The second interface of the first valve is connected to the first interface of the second valve, the second interface of the second valve is connected to the first interface of the third valve, and the third valve The second interface of the fourth valve is connected to the first interface of the fourth valve, the second interface of the fourth valve is connected to the first interface of the fifth valve, and the second interface of the fifth valve is connected to the first interface of the fourth valve. The first interface of the six valves is connected;

The first recovery container is respectively connected to the first negative pressure pipeline and the third interface of the first valve;

The first reagent container is connected to the third interface of the second valve;

A first syringe connected to the third interface of the third valve;

18 F ion enrichment chamber, connected to the third interface of the fourth valve and the third interface of the fifth valve between mouth;

The second syringe is connected to the third interface of the sixth valve.
The device of claim 2, wherein,

The preprocessing module also includes:

A first linear drive device capable of driving the piston of the first syringe to move within the empty barrel;

A second linear drive device capable of driving the piston of the second syringe to move within the empty barrel.
The device of claim 2, wherein,

The preprocessing module also includes:

Positive pressure and negative pressure pipelines and liquid adding pipelines respectively pass through the piston of the second syringe and extend into the second syringe.
The device of claim 2, wherein,

The reaction module includes:

The seventh valve, the eighth valve, the ninth valve, the tenth valve, the eleventh valve, the twelfth valve, and the thirteenth valve, the seventh valve to the thirteenth valve respectively include at least a first interface, The second interface, the third interface, and the seventh valve to the thirteenth valve can realize conduction of any two interfaces of the three interfaces or non-conduction of all three interfaces; the seventh valve The first interface is connected to the pretreatment module, the second interface of the seventh valve is connected to the first interface of the eighth valve, the second interface of the eighth valve is connected to the first interface of the ninth valve. The interfaces are connected, the second interface of the ninth valve is connected to the first interface of the tenth valve, the second interface of the tenth valve is connected to the first interface of the eleventh valve, the tenth valve The second interface of a valve is connected to the first interface of the twelfth valve, the second interface of the twelfth valve is connected to the first interface of the thirteenth valve, and the third interface of the twelfth valve is connected to the first interface of the twelfth valve. Three interfaces are connected to the purification module;

The reaction vessel is respectively connected to the second negative pressure pipeline and the third interface of the seventh valve;

A temperature control component for heating and/or cooling the reaction vessel;

a second reagent container connected to the third interface of the eighth valve;

A third syringe connected to the third interface of the ninth valve;

A third reagent container is connected to the third interface of the tenth valve;

a fourth reagent container connected to the third interface of the eleventh valve;

The fifth reagent container is connected to the third interface of the thirteenth valve.
The device of claim 5, wherein,

The reaction module also includes:

A third linear drive device capable of driving the piston of the third syringe to move within the empty barrel.
The device of claim 5, wherein,

The purification module includes:

A fourteenth valve, the fourteenth valve includes at least a first interface, a second interface, a third interface, a fourth interface, a fifth interface, and a sixth interface, wherein the fourteenth valve can operate in the first mode and second mode, the first mode is that the first interface is connected to the second interface, the third interface is connected to the fourth interface, and the fifth interface is connected to the sixth interface; the second mode is The second interface is connected to the third interface, the fourth interface is connected to the fifth interface, and the sixth interface is connected to the first interface; the fourth interface of the fourteenth valve is connected to the reaction module;

Chromatography column assembly, one end of the chromatography column assembly is connected to the second interface of the fourteenth valve;

A quantitative loop, both ends of which are respectively connected to the third interface of the fourteenth valve and the sixth interface of the fourteenth valve;

a liquid transfer pump, connected to the first interface of the fourteenth valve;

The second recovery container is connected to the fifth interface of the fourteenth valve;

A fifteenth valve, the fifteenth valve includes at least a first interface, a second interface, and a third interface, The fifteenth valve can achieve communication between the first interface and the second interface or the first interface and the third interface; the first interface of the fifteenth valve is connected to the other end of the chromatography column assembly, so The second interface of the fifteenth valve is connected to the prescription module, and the third interface of the fifteenth valve is connected to the second recovery container.
The device of claim 7, wherein

The prescription module includes:

A sixteenth valve and a seventeenth valve, the sixteenth valve and the seventeenth valve respectively include at least a first interface, a second interface, and a third interface, and the sixteenth valve and the tenth valve Each of the seven valves can achieve conduction of any two of the three interfaces or non-conduction of all three interfaces; wherein, the first interface of the sixteenth valve is connected to the second interface of the thirteenth valve, The second interface of the sixteenth valve is connected to the first interface of the seventeenth valve, the third interface of the sixteenth valve is connected to the purification module, and the second interface of the seventeenth valve Connected to the third negative pressure pipeline;

Finished product collection containers;

The transfer container is respectively connected to the third interface of the seventeenth valve, the finished product collection container, and the fourth negative pressure pipeline.
A method for producing a liquid composition of Compound I, using the equipment according to any one of claims 1 to 8, including:

Use the preprocessing module to enrich 18 F ions;

Use the reaction module to react the enriched 18 F ions with the precursor of compound I to generate compound I tert-butyl ester, and perform a de-tert-butyl esterification reaction on compound I tert-butyl ester to obtain compound I crude product;

Use the purification module to purify the crude compound I to obtain the pure compound I;

Use the formulation module to formulate the purified pure compound I into a compound I liquid composition.
The use of the equipment according to any one of claims 1 to 8 in the production of compound I liquid composition use.