A production apparatus of a liquid composition, and a preparation method and use thereof
By designing automated compound I production equipment, the problems of high material consumption, complex operation, and low yield of existing equipment have been solved, achieving efficient preparation of compound I liquid compositions and meeting the needs of multiple users.
Patent Information
- Application Number
- CN202310204871.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-06-07
- Publication Date
- 2026-01-23
- Estimated Expiration
- 2042-06-07
AI Technical Summary
Existing equipment for producing liquid compositions of Compound I involves numerous consumables, complex processes, and low yields. Each preparation can only meet the needs of 1 to 2 people, thus limiting its clinical use.
A production device comprising a pretreatment module, a reaction module, a purification module, and a formulation module was designed. The device achieves automated operation through an electric control valve and a linear drive device. It enriches 18F ions and reacts them with the precursor of compound I to generate compound I tert-butyl ester. The precursor then undergoes detert-butyl esterification and purification to finally prepare a liquid composition of compound I.
The process operation was simplified, the yield was improved, a single preparation could meet the needs of multiple users, and the equipment was automated.
Smart Images
Figure CN116351339B_ABST
Abstract
Description
[0001] This application is a divisional application of Chinese invention patent application No. 202210635474.8, filed on June 7, 2022, entitled "A production equipment for a liquid composition and its preparation method and use". Technical Field
[0002] This application relates to the field of radiopharmaceutical technology, specifically to a production apparatus for a liquid composition, its preparation method, and its uses. Background Technology
[0003] According to data from a research report by the Chinese Center for Disease Control and Prevention, the proportion and absolute number of deaths from coronary heart disease (CHD) in the Chinese population have increased significantly. In 2013, the total number of CHD deaths in China was 1.394 million, an increase of 90% compared to 1990. Currently, CHD is the leading cause of death in six provinces and municipalities in my country. With the increasing aging population, the incidence and mortality rates of CHD in my country will continue to rise.
[0004] With the development of clinical cardiology, the focus has gradually shifted from the diagnosis of coronary artery disease to risk stratification and prognosis. Currently, it is widely believed that information such as myocardial ischemia, cardiac function, and viable myocardium provides the primary basis for risk stratification, prognosis, and treatment planning in coronary artery disease. Therefore, identifying viable myocardium is of significant clinical importance and is a hot topic in clinical treatment and related event prediction. Currently, radionuclide myocardial scintigraphy remains the gold standard for in vivo assessment of viable myocardium.
[0005] 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 radioactive nuclide 18 F-labeled modified fatty acids (MFAs) are structurally very similar to naturally occurring free fatty acids (FFAs) in the human body. They can be taken up by cardiomyocytes and used in positron emission tomography (PET) imaging to evaluate cardiomyocyte viability. The structure of compound I is shown in the figure below:
[0006]
[0007] Compound I can be visualized 5 minutes after intravenous injection, demonstrating high compliance and clinical benefits.
[0008] Current equipment requires a lot of consumable materials for synthesis, has a complex process, and a low yield. A single preparation can only meet the needs of 1 to 2 people, which limits its clinical use.
[0009] Therefore, it is particularly important to develop an apparatus for producing liquid compositions of Compound I (such as injection solutions). Summary of the Invention
[0010] To address the problems in the prior art, this application provides equipment for producing liquid compositions of Compound I (such as injection solutions) and a method for preparing the same. The technical solution of this application is as follows:
[0011] 1. Equipment for producing liquid compositions of compound I, including:
[0012] Preprocessing module for enrichment 18 F ions;
[0013] The reaction module is used to process the enriched product. 18 F ions react with the precursor of compound I to generate tert-butyl ester of compound I, and then the tert-butyl ester of compound I undergoes a detert-butylation reaction to obtain crude compound I;
[0014] The purification module is used to purify the crude compound I to obtain the pure compound I.
[0015] The formulation module formulates the purified compound I into a liquid composition of compound I.
[0016]
[0017] 2. The device as described in item 1, wherein the preprocessing module comprises:
[0018] A first valve, a second valve, a third valve, a fourth valve, a fifth valve, and a sixth valve, wherein each of the first to sixth valves includes at least a first interface, a second interface, and a third interface, and each of the first to sixth valves is capable of either having any two of the three interfaces connected or having all three interfaces de-connected; the first interface of the first valve is connected to a first positive pressure pipeline, 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, the second interface of the third 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 sixth valve;
[0019] The first recovery container is connected to the first negative pressure pipeline and the third interface of the first valve, respectively;
[0020] The first reagent container is connected to the third port of the second valve;
[0021] The first syringe is connected to the third port of the third valve;
[0022] 18The F-ion enrichment chamber is connected between the third port of the fourth valve and the third port of the fifth valve.
[0023] The second syringe is connected to the third port of the sixth valve.
[0024] Preferably, the first valve, the second valve, the third valve, the fourth valve, the fifth valve, and the sixth valve are all electrically controlled valves.
[0025] 3. The device as described in item 2, wherein the preprocessing module further includes:
[0026] A first linear drive device, which can drive the piston of the first syringe to move inside the empty cylinder;
[0027] The second linear drive device is capable of driving the piston of the second syringe to move inside the empty cylinder.
[0028] 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 lead screw;
[0029] More preferably, both the first linear drive device and the second linear drive device are lead screws, and the lead screws are driven by stepper motors.
[0030] 4. The device as described in item 2, wherein the preprocessing module further includes:
[0031] Positive and negative pressure lines and liquid addition lines are provided, which respectively pass through the piston of the second syringe and extend into the second syringe.
[0032] Preferably, a flow meter is installed on the liquid addition pipeline.
[0033] 5. The device as described in item 2, wherein the reaction module comprises:
[0034] The system comprises a seventh valve, an eighth valve, a ninth valve, a tenth valve, an eleventh valve, a twelfth valve, and a thirteenth valve. Each of the seventh to thirteenth valves includes at least a first interface, a second interface, and a third interface. Each of the seventh to thirteenth valves is capable of either having any two of its three interfaces connected or having all three interfaces deactivated. The first interface of the seventh valve 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 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 second interface of the eleventh 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. The third interface of the twelfth valve is connected to the purification module.
[0035] The reaction vessel is connected to the second negative pressure pipeline and the third port of the seventh valve, respectively;
[0036] Temperature control components for heating and / or cooling the reaction vessel;
[0037] The second reagent container is connected to the third port of the eighth valve;
[0038] The third syringe is connected to the third port of the ninth valve;
[0039] The third reagent container is connected to the third port of the tenth valve;
[0040] The fourth reagent container is connected to the third port of the eleventh valve;
[0041] The fifth reagent container is connected to the third interface of the thirteenth valve.
[0042] Preferably, the seventh, eighth, ninth, tenth, eleventh, twelfth and thirteenth valves are all electrically controlled valves.
[0043] 6. The device as described in item 5, wherein the reaction module further includes:
[0044] The third linear drive device is capable of driving the piston of the third syringe to move inside the empty cylinder.
[0045] Preferably, the third linear drive device is selected from one of a pneumatic rod, a hydraulic rod, and a lead screw;
[0046] More preferably, the third linear drive device is a lead screw, which is driven by a stepper motor.
[0047] 7. The apparatus as described in item 5, wherein the purification module comprises:
[0048] 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. The fourteenth valve is switchable between a first mode and a second mode. In the first mode, the first interface is connected to the second interface, the third interface to the fourth interface, and the fifth interface to the sixth interface. In the second mode, the second interface is connected to the third interface, the fourth interface to the fifth interface, and the sixth interface to the first interface. The fourth interface of the fourteenth valve is connected to the reaction module.
[0049] A chromatographic column assembly, one end of which is connected to the second interface of the fourteenth valve;
[0050] A metering loop, with its two ends connected to the third port of the fourteenth valve and the sixth port of the fourteenth valve, respectively;
[0051] A liquid transfer pump is connected to the first interface of the fourteenth valve;
[0052] The second recovery container is connected to the fifth interface of the fourteenth valve;
[0053] The fifteenth valve includes at least a first interface, a second interface, and a third interface, and the fifteenth valve is capable of enabling the first interface to be connected to the second interface or the first interface to be connected to the third interface; the first interface of the fifteenth valve is connected to the other end of the chromatographic column assembly, the second interface of the fifteenth valve is connected to the formulation module, and the third interface of the fifteenth valve is connected to the second recovery container.
[0054] Preferably, the fourteenth valve and the fifteenth valve are both electrically controlled valves.
[0055] 8. The device as described in item 7, wherein the prescription module comprises:
[0056] The sixteenth valve and the seventeenth valve each include at least a first interface, a second interface, and a third interface, and both the sixteenth valve and the seventeenth valve are capable of making any two of the three interfaces conductive or making all three interfaces non-conductive; 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 is connected to the third negative pressure pipeline;
[0057] Finished product collection container;
[0058] The transfer container is connected to the third port of the seventeenth valve, the finished product collection container, and the fourth negative pressure pipeline, respectively.
[0059] 9. A method for producing a liquid composition of compound I, using the equipment described in any one of items 1 to 8, comprising:
[0060] Use a preprocessing module to enrich 18 F ions;
[0061] Use reaction modules to enrich 18 F ions react with the precursor of compound I to generate tert-butyl ester of compound I, and then the tert-butyl ester of compound I undergoes a detert-butylation reaction to obtain crude compound I;
[0062] The crude compound I was purified using a purification module to obtain the pure compound I.
[0063] The purified compound I was formulated into a liquid composition using the formulation module.
[0064] 10. Use of the equipment described in any one of items 1 to 8 in the production of liquid compositions of compound I.
[0065] The apparatus provided in this application for producing a liquid composition of Compound I can prepare a crude product of Compound I, and further purify and formulate the crude product to obtain a liquid composition of Compound I for direct clinical use. The process is simple, has a high yield, and can meet the needs of multiple users in a single preparation. Furthermore, the equipment can be automated by controlling various valves through a microprocessor control system (such as a PLC). This application also provides a method for using the aforementioned equipment.
[0066] The above description is merely an overview of the technical solution of this application. In order to make the technical means of this application clearer and more understandable, so that those skilled in the art can implement it according to the contents of the specification, and in order to make the above and other objects, features and advantages of this application more obvious and understandable, the following is an example of a specific implementation of this application. Attached Figure Description
[0067] Figure 1 : Schematic diagram of the pretreatment module, reaction module, and formulation module assembly of the equipment for producing compound I;
[0068] Figure 2 (a)~ Figure 2 (b): Schematic diagram of the purification module of the equipment for producing compound I (the purification module is through...) Figure 2 (a) Pattern and Figure 2 (b) Purification is performed by switching between modes;
[0069] Figure 3 (a)~ Figure 3 (h): Schematic diagram of a three-way valve ( Figure 3 (a) is a schematic diagram showing that all three ports of the three-way valve are connected; Figure 3 (b)~ Figure 3 (d) are schematic diagrams showing the connection between the two ports in a three-way valve; Figure 3 (e)~ Figure 3 (h) are schematic diagrams showing that the three ports of the three-way valve are not connected to each other;
[0070] Figure 4 (a)~ Figure 4 (d): For Figure 3 A simplified diagram of a three-way valve ( Figure 4 (a) is the corresponding Figure 3 (b) Schematic diagram of a three-way valve; Figure 4 (b) is the corresponding Figure 3(c) Schematic diagram of a three-way valve; Figure 4 (c) is the corresponding Figure 3 (d) A simplified diagram of a three-way valve; Figure 4 (d) is the corresponding Figure 3 (e)~ Figure 3 (h) A simplified diagram of a three-way valve;
[0071] Figure 5 (a)~ Figure 5 (b): Schematic diagram of a six-way valve Figure 5 (a) Figure 5 (b) are schematic diagrams of the six-way valve core in different working positions;
[0072] Figure 6 (a)~ Figure 6 (c): Schematic diagram of the working principle of the preprocessing module (the preprocessing module is arranged according to...) Figure 6 (a)~ Figure 6 (c) Sequential implementation 18 F ions are enriched and fed into the reaction module;
[0073] Figure 7 (a)~ Figure 7 (h): Schematic diagram of the working principle of the reaction module (the reaction module is arranged according to...) Figure 7 (The reactions proceed in the following order: (a), 7(b), 7(c), 7(d), 7(e), 7(d), 7(b), 7(f), 7(d), 7(g), 7(d), 7(h));
[0074] Figure 8 (a)~ Figure 8 (b): Schematic diagram of the working principle of the prescription module (the prescription module is arranged according to...) Figure 8 (a) and (b) are sequentially prescribed and the final product is collected.
[0075] Figure 9 Schematic diagram of the main negative pressure pipeline connection.
[0076] Explanation of reference numerals in the attached figures:
[0077] 1-17, valves 1-17; V1, three-way valve body; V2, three-way valve core; V3, six-way valve body; V4, six-way valve core;
[0078] 18. First recovery container; 19. First reagent container; 20. First syringe; 21. 18 F-ion enrichment chamber; 22. Second syringe; 23. Positive and negative pressure pipelines; 24. Liquid addition pipeline;
[0079] 25. Reaction vessel; 26. Second reagent container; 27. Third syringe; 28. Third reagent container; 29. Fourth reagent container; 30. Fifth reagent container;
[0080] 31. Column assembly; 32. Quantitative loop; 33. Liquid transfer pump; 34. Second recovery container;
[0081] 35. Transfer container; 36. Finished product collection container;
[0082] 37. Third recycling container;
[0083] P0, positive pressure pipeline of positive and negative pressure pipelines; P1, first positive pressure pipeline;
[0084] N, main negative pressure pipeline; N0, negative pressure pipeline of positive and negative pressure pipelines; N1, first negative pressure pipeline; N2, second negative pressure pipeline; N3, third negative pressure pipeline; N4, fourth negative pressure pipeline. Detailed Implementation
[0085] The following embodiments of this application are only used to illustrate specific implementation methods of this application, and these embodiments should not be construed as limitations on this application. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of this application shall be considered equivalent substitutions and fall within the protection scope of this application.
[0086] This embodiment provides a method for producing trans-2-[2-(5-[ 18 An apparatus for producing a liquid composition (such as an injection) of [F]fluorotridecyl]cyclopropyl]acetic acid (hereinafter referred to as "Compound I") includes:
[0087] Preprocessing module for enrichment 18 F ions;
[0088] Reaction module, used for enrichment 18 F ions react with the precursor of compound I to generate tert-butyl ester of compound I, and then the tert-butyl ester of compound I undergoes a detert-butylation reaction to obtain crude compound I;
[0089] The purification module is used to purify the crude compound I to obtain the pure compound I.
[0090] The formulation module formulates the purified compound I into a liquid composition of compound I.
[0091] As shown in the figure below, compound I uses the precursor of compound I and radioactive fluorine [ 18 The product is prepared from fluorine [F] ions via a two-step reaction. The first step involves the reaction of fluorine [F] ions with fluorine [F] ions. 18[F] Nucleophilic substitution of the methanesulfonyloxy group (-OMs) in the precursor of compound I yields tert-butyl ester of compound I. In the second step, without separation and purification, a detert-butylation reaction is carried out by adding trifluoroacetic acid / acetonitrile solution to obtain crude compound I. The synthetic route of crude compound I is shown in the figure below.
[0092]
[0093] In the diagram, K 222 It is 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane, abbreviated as amino polyether.
[0094] Therefore, it can be understood that the process for preparing the crude compound I in this application is different from that in the applicant's other application. As a result, the applicant made corresponding improvements to the production equipment, which led to this application.
[0095] This embodiment provides an apparatus for producing liquid compositions of compound I (such as injection solutions), which first enriches the compound through a pretreatment module. 18 F ions; enriched 18 F ions enter the reaction module and react with the precursor of compound I to generate tert-butyl ester of compound I. The tert-butyl ester of compound I then undergoes a detert-butylation reaction to obtain crude compound I. The crude compound I enters the purification module for purification to obtain pure compound I. Furthermore, the pure compound I enters the formulation module and is formulated into a liquid composition of compound I.
[0096] Through the technical solution of this embodiment, crude compound I can be obtained, and the crude compound I can be purified and formulated for direct clinical use.
[0097] Additionally, it should be noted that "crude product" and "pure product" in this application refer to the products before and after purification, respectively; "formulation" in this embodiment specifically refers to preparing a liquid composition of compound I by combining the pure compound I with excipients.
[0098] In one embodiment, such as Figure 1 , Figure 3 , Figure 4 and Figure 6 The preprocessing module includes:
[0099] A first valve 1, a second valve 2, a third valve 3, a fourth valve 4, a fifth valve 5, and a sixth valve 6, wherein each of the first valves 1 to 6 includes at least a first interface, a second interface, and a third interface, and each of the first valves 1 to 6 can either make any two of the three interfaces conductive or make all three interfaces non-conductive; the first interface of the first valve 1 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, the second interface of the second valve 2 is connected to the first interface of the third valve 3, 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, and the second interface of the fifth valve 5 is connected to the first interface of the sixth valve 6.
[0100] The first recycling container 18 is connected to the first negative pressure pipeline N1 and the third interface of the first valve 1, respectively.
[0101] The first reagent container 19 is connected to the third port of the second valve 2, and the first reagent container 19 is used to hold... 18 F rinsing solution (e.g., acetonitrile + water + potassium) 222 +K2CO3, etc.);
[0102] The first syringe 20 is connected to the third port of the third valve 3;
[0103] 18 The F-ion enrichment chamber 21 is connected between the third port of the fourth valve 4 and the third port of the fifth valve 5. 18 The F-ion enrichment chamber 21 is filled with anion exchange resin.
[0104] The second syringe 22 is connected to the third port of the sixth valve 6;
[0105] 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 electrically controlled valves (such as solenoid valves).
[0106] First, such as Figure 3 As shown, 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 functions of the seventh valve 7 to the thirteenth valve 13, the sixteenth valve 16, and the seventeenth valve 17 mentioned below, which will not be elaborated further below.
[0107] Specifically, such as Figure 3 (a)~ Figure 3As shown in (h), the three-way valve includes a circular three-way valve core V2 and a three-way valve body V1 outside the valve core V2. The valve body V1 has a first interface ① on its left side, a second interface ② on its right side, and a third interface ③ on its upper side. A T-shaped flow channel is provided inside the valve core V2. By rotating the valve core V2, the first interface ① and the third interface ③ can be connected. Figure 3 (b) shows that the first interface ① and the second interface ② are connected (as shown in the diagram). Figure 3 (c) shows that the second interface ② and the third interface ③ are connected (as shown in the figure). Figure 3 (d) shows that none of the three interfaces are connected (as shown in the diagram). Figure 3 (e)~ Figure 3 (as shown in (h)). Furthermore, based on the above-described three-way valve structure, those skilled in the art, according to existing technology, know how to control the rotation of the three-way valve core V2 relative to the three-way valve body V1 by a fixed angle to achieve electric (electromagnetic) control of the three-way valve (e.g., using a stepper motor to control the rotation of the three-way valve core V2). Additionally, to simplify the description of the state of the three-way valve below, Figure 4 Given Figure 3 A simplified diagram of a three-way valve, in which... Figure 4 (a) is the corresponding Figure 3 (b) Schematic diagram of a three-way valve; Figure 4 (b) is the corresponding Figure 3 (c) Schematic diagram of a three-way valve; Figure 4 (c) is the corresponding Figure 3 (d) A simplified diagram of a three-way valve; Figure 4 (d) is the corresponding Figure 3 (e)~ Figure 3 (h) A simplified diagram of a three-way valve.
[0108] Furthermore, the first negative pressure line N1 specifically provides negative pressure through vacuuming. Similarly, the negative pressure lines N0, N2, N3, and N4 of the positive and negative pressure lines described below can also provide negative pressure through vacuuming, and will not be elaborated upon further. Moreover, each of the positive and negative pressure lines—N0, N1, N2, N3, and N4—can be individually connected to a vacuuming device, or two or more can be connected to a single vacuuming device / line. Specifically, for example… Figure 9 As shown, the third recovery container 37 is connected to the main negative pressure pipeline N, and other negative pressure pipelines (one or more of the following: negative pressure pipeline N0, first negative pressure pipeline N1, second negative pressure pipeline N2, third negative pressure pipeline N3, and fourth negative pressure pipeline N4) are also connected to the third recovery container 37 (specifically as follows). Figure 9(The pipeline is connected to the left side of the third recovery container 37), so that a vacuum device can drive more than one negative pressure pipeline to work, and the third recovery container 37 can store the liquid flowing in from the negative pressure pipeline.
[0109] The first positive pressure line P1 provides positive pressure by blowing out an inert gas (such as nitrogen or argon). Additionally, a filter membrane can be installed in the first positive pressure line P1 to ensure the cleanliness of the inert gas entering the equipment. The positive pressure line P0 of the positive and negative pressure lines described below can also provide positive pressure in this way, and will not be elaborated further below.
[0110] Furthermore, those skilled in the art will know that, generally, control valves (such as electric control valves, specifically solenoid valves) can be installed on the negative pressure pipeline N0, the first negative pressure pipeline N1, the second negative pressure pipeline N2, the third negative pressure pipeline N3, the fourth negative pressure pipeline N4, the positive pressure pipeline P0, and the first positive pressure pipeline P1 of the positive and negative pressure pipelines to control the opening and closing of the pipelines, and / or flow valves / flow meters can be installed to control the magnitude of positive / negative pressure, etc., which will not be elaborated further in this document.
[0111] Those skilled in the art will understand that the empty cylinder and the piston inside the cylinder are essential components of a syringe. The piston can be an elongated structure, and its relative movement to the empty cylinder can be achieved by pushing the portion of the piston located outside the cylinder; alternatively, the piston can simply be a sealing rubber tip located inside the empty cylinder, in which case a core rod is mounted on the piston, and pushing the core rod can drive the relative movement between the piston and the empty cylinder. Figure 1 As shown in the figure, the syringe structure consists of an empty cylinder, a piston, and a core rod.
[0112] Preprocessing module enrichment 18 The specific process of F ion formation can be described as follows: Figure 6 (a)~ Figure 6 As shown in (c)
[0113] Initially, the states of valves 1 through 6 are as follows: Figure 6 As shown in (a), at this time, the first negative pressure line N1 is evacuated. Then the second syringe 22 will contain... 18 F ions oxygen [ 18 O] Eighteen Water (a type of card game) is launched, including 18 F ions oxygen [ 18 O] Eighteen streams flow through 18 F-ion enrichment chamber 21 hours 18 F ions in 18 The F-ion is enriched in the enrichment chamber 21, and the remaining liquid flows into the first recovery container 18.
[0114] Afterwards, the states of the second valve 2 to the third valve 3 are as follows: Figure 6As shown in (b), the first syringe 20 is drawn into the first reagent container 19. 18 F rinsing solution;
[0115] Finally, the states of valves 3 through 6 are as follows: Figure 6 As shown in (c), the first syringe 20 will... 18 F rinsing solution is then released. 18 F-eluent will be enriched 18 F-ion enrichment chamber 18 F ions are introduced into the reaction module.
[0116] This embodiment provides a specific preprocessing module that can simply and conveniently process... 18 F ions were enriched and the enriched ions were then... 18 F-ion rinsing is used to deliver the sample to the subsequent reaction module. This is especially true when the valves, positive pressure lines, negative pressure lines, and syringes are automatically controlled, enabling... 18 The automated processing of F ion enrichment, rinsing, and delivery into the reaction module.
[0117] In one embodiment, the preprocessing module further includes:
[0118] A first linear drive device (not shown in the attached drawings) is capable of driving the piston of the first syringe 20 to move inside the empty cylinder.
[0119] A second linear drive device (not shown in the attached drawings) is capable of driving the piston of the second syringe 22 to move inside the empty cylinder;
[0120] 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 lead screw;
[0121] More preferably, both the first linear drive device and the second linear drive device are lead screws, and the lead screws are driven by stepper motors.
[0122] In this embodiment, the first syringe 20 and the second syringe 22 are controlled by setting a first linear drive device and a second linear drive device.
[0123] When using pneumatic or hydraulic rods in conjunction with PLC or other controllers, it is convenient to achieve automatic control of the first syringe 20 and the second syringe 22.
[0124] Using a lead screw allows for precise control of the piston stroke in the first syringe 20 and the second syringe 22. Especially when the lead screw is driven by a stepper motor, it facilitates automatic and precise control of the first syringe 20 and the second syringe 22 in conjunction with a microprocessor control system (PLC, etc.). The lead screw driven by the stepper motor can be assembled by the user or a ready-made electric actuator (a type of lead screw system) can be purchased directly.
[0125] In one embodiment, such as Figure 1 As shown, the pretreatment module also includes a positive pressure / negative pressure pipeline 23 and a liquid addition pipeline 24, which respectively pass through the piston of the second syringe 22 and extend into the closed space formed by the piston and the empty cylinder of the second syringe 22.
[0126] Preferably, a flow meter is provided on the liquid addition pipeline 24 to control the liquid addition amount, and / or a control valve (such as an electric control valve, specifically a solenoid valve) is provided on the liquid addition pipeline 24 to control the opening and closing of the pipeline, thereby controlling whether liquid is added.
[0127] In this application, the positive and negative pressure pipeline 23 is a pipeline in which the positive pressure pipeline P0 and the negative pressure pipeline N0 are connected, and the piston (e.g., ...) passes through this pipeline. Figure 1 (as shown); or, the positive pressure pipeline P0 and the negative pressure pipeline N0 of the positive and negative pressure pipelines respectively pass through the piston.
[0128] Therefore, this application provides a method for adding liquid (containing...) to the second syringe 22. 18 F ions oxygen [ 18 The proposed solution (O] 18-water) involves adding liquid through a liquid addition line. Simultaneously, to prevent excessive pressure in the second syringe 22, a vacuum is created through the negative pressure line N0 of the positive and negative pressure lines, thus achieving liquid addition. After liquid addition, the liquid in the second syringe 22 can be discharged for further processing by pushing the piston down or by releasing inert gas (pressurizing) through the positive pressure line P0 of the positive and negative pressure lines.
[0129] This embodiment provides a method for adding liquid to the second syringe 22. This allows for the provision of more liquid containing... 18 F ions oxygen [ 18 O] Eighteen Waters to be used 18 F ion enrichment provides more and more fuel for subsequent reactions. 18 F ions. Positive pressure can be provided through the positive pressure line P0 of the positive and negative pressure lines to add liquid to subsequent processes, or the liquid can be added to subsequent processes more precisely by pushing the piston.
[0130] In one embodiment, such as Figure 1 As shown, the reaction module includes:
[0131] The system comprises a seventh valve (7), an eighth valve (8), a ninth valve (9), a tenth valve (10), an eleventh valve (11), a twelfth valve (12), and a thirteenth valve (13). Each of the seventh to thirteenth valves includes at least a first interface, a second interface, and a third interface. Each of the seventh to thirteenth valves is capable of either having any two of its three interfaces connected or having all three interfaces disconnected. The first interface of the seventh valve is connected to the pretreatment module (the second interface of the sixth valve 6). The second interface of the seventh valve is connected to the first interface of the eighth valve (8). The second interface of the eighth valve (8) is connected to the first interface of the ninth valve (9). The second interface of the ninth valve (9) is connected to the first interface of the tenth valve (10). The second interface of the tenth valve (10) is connected to the first interface of the eleventh valve (11). The second interface of the eleventh valve (11) is connected to 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). The third interface of the twelfth valve (12) is connected to the purification module (the fourth interface of the fourteenth valve (14)).
[0132] The reaction vessel 25 is connected to the second negative pressure pipeline N2 and the third interface of the seventh valve 7, respectively. Preferably, a control valve (such as an electric control valve, specifically a solenoid valve) is provided on the pipeline between the second negative pressure pipeline N2, the reaction vessel 25 and the third interface of the seventh valve 7. The control valve can control the opening and closing of the pipeline, thereby ensuring that the reaction takes place in the reaction vessel 25.
[0133] A temperature control component (not shown in the attached figure) is used to heat and / or cool the reaction vessel 25. Heating can be performed by electric heating and cooling can be performed by air cooling. The specific implementation can be referred to the prior art, and will not be described in detail here.
[0134] The second reagent container 26 is connected to the third interface of the eighth valve 8, and the second reagent container 26 is used to hold the acetonitrile solution of the precursor of compound I;
[0135] The third syringe 27 is connected to the third port of the ninth valve 9;
[0136] The third reagent container 28 is connected to the third port of the tenth valve 10, and the third reagent container 28 is used to hold TFA / ACN (trifluoroacetic acid / acetonitrile) solution;
[0137] The fourth reagent container 29 is connected to the third port of the eleventh valve 11, and the fourth reagent container 29 is used to hold water (sterile water for injection);
[0138] 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 anhydrous ethanol;
[0139] 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 electrically controlled valves (such as solenoid valves).
[0140] The structures of the seventh valve 7 to the thirteenth valve 13, the third syringe 27, etc. in this embodiment have been described above and will not be repeated here.
[0141] The specific process of the reaction module carrying out the reaction is as follows: Figure 7 (a)~ Figure 7 As shown in (h),
[0142] Initially, the state of valve 7 is as follows: Figure 7 As shown in (a), at this point, the preprocessing module will enrich the... 18 F ions and the like enter the reaction vessel 25 (which can be a reaction flask) through the seventh valve 7.
[0143] Afterwards, the states of valves 1 through 7 are as follows: Figure 7 As shown in (b), at this time, the first positive pressure pipeline P1 outputs positive pressure (inputs inert gas) into the reaction vessel 25, the second negative pressure pipeline N2 performs evacuation, and the temperature control component heats the reaction vessel 25 to remove the solvent. The heating temperature at this time is 80-130°C, thereby obtaining the activated product. 18 F ions.
[0144] Afterwards, the states of valves 8 through 9 are as follows: Figure 7 As shown in (c), the third syringe 27 draws acetonitrile solution of the precursor of compound I from the second reagent container 26;
[0145] Afterwards, the states of valves 7 through 9 are as follows: Figure 7 As shown in (d), the third syringe 27 draws the acetonitrile solution containing 1-10 mg of the compound I precursor (acetonitrile solution).
[0146] 0.2-2.0 ml) is pushed into reaction vessel 25; the temperature control component is used for heating, and the reaction is carried out under sealed conditions at 90-140℃ for 2-20 min, where the precursor of compound I reacts with K. 18 F / K 222 A nucleophilic substitution reaction was carried out to produce compound I, tert-butyl ester;
[0147] Afterwards, the states of valves 9 through 10 are as follows: Figure 7 As shown in (e), the third syringe 27 draws the TFA / ACN solution contained in the third reagent container 28;
[0148] Afterwards, the states of valves 7 through 9 are as follows: Figure 7 As shown in (d), the third syringe 27 pushes the extracted TFA / ACN solution (0.2-2.0 ml of 10-50% TFA / ACN solution) into the reaction vessel 25; the temperature control component heats the mixture, and the substance reacts in the reaction vessel 25 at 30-100°C for 1-30 min to remove the tert-butyl ester protecting group.
[0149] After the reaction cools down, the states of valves 1 through 7 are as follows: Figure 7 As shown in (b), the first positive pressure line P1 outputs positive pressure into the reaction vessel 25, the second negative pressure line N2 performs vacuuming, and the temperature control component heats the reaction vessel 25 to remove TFA / ACN.
[0150] Afterwards, the states of valves 9 through 11 are as follows: Figure 7 As shown in (f), the third syringe 27 draws water from the fourth reagent container 29;
[0151] Afterwards, the states of valves 7 through 9 are as follows: Figure 7 As shown in (d), the third syringe 27 pushes the extracted water into the reaction vessel 25;
[0152] Afterwards, the states of valves 9 through 13 are as follows: Figure 7 As shown in (g), the third syringe 27 draws anhydrous ethanol from the fifth reagent container 30;
[0153] Afterwards, the states of valves 7 through 9 are as follows: Figure 7 As shown in (d), the third syringe 27 pushes the extracted anhydrous ethanol into the reaction vessel 25;
[0154] Afterwards, the states of valves 7 through 9 remained as before. Figure 7 (d) shows the liquid drawn from the reaction vessel 25 by the third syringe 27;
[0155] Finally, the states of valves 9 through 12 are as follows: Figure 7 As shown in (h), the third syringe 27 pushes the liquid extracted from the reaction container 25 into the purification module.
[0156] This embodiment provides a specific reaction module. By changing the operating states of the seventh valve 7 to the thirteenth valve 13, and through the coordinated operation of the first positive pressure pipeline P1, the second negative pressure pipeline N2, the reaction vessel 25, and the temperature control components, the reaction of compound I precursor and K is cleverly achieved using a simple device. 18 F / K 222The reaction proceeds via nucleophilic substitution to produce compound I tert-butyl ester and detert-butylation of compound I tert-butyl ester. In particular, when the valves, positive pressure lines, negative pressure lines, and syringes are automatically controlled, the above two-step reaction can be automated.
[0157] In one embodiment, the reaction module further includes:
[0158] A third linear drive device (not shown in the attached drawings) is capable of driving the piston of the third syringe 27 to move inside the empty cylinder;
[0159] Preferably, the third linear drive device is selected from one of a pneumatic rod, a hydraulic rod, and a lead screw;
[0160] More preferably, the third linear drive device is a lead screw, which is driven by a stepper motor.
[0161] In this embodiment, the third syringe 27 is controlled by setting a third linear drive device.
[0162] When using pneumatic or hydraulic rods in conjunction with PLC or other controllers, it is convenient to achieve automatic control of the third injector 27.
[0163] Using a lead screw allows for precise control of the piston stroke in the third injector 27. This is especially beneficial when the lead screw is driven by a stepper motor, facilitating automatic and precise control of the third injector 27 in conjunction with a microprocessor control system (PLC, etc.). The stepper motor-driven lead screw can be assembled independently or a ready-made electric actuator (a type of lead screw system) can be purchased directly.
[0164] In one embodiment, such as Figure 2 As shown, the purification module includes:
[0165] 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...). Figure 5 (①~⑥) wherein, the fourteenth valve 14 can switch between a first mode and a second mode. In the first mode, 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; in the second mode, 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 14 is connected to the reaction module (the third interface of the twelfth valve 12) (pipeline A is connected to pipeline A').
[0166] Chromatographic column assembly 31, one end of which is connected to the second interface of the fourteenth valve 14;
[0167] The quantitative loop 32 (also called the injection loop) has its two ends connected to the third port and the sixth port of the fourteenth valve 14, respectively.
[0168] Liquid transfer pump 33 is connected to the first interface of the fourteenth valve 14 and is used to transfer fluid (a solution of ethanol and water in a ratio of ethanol / water = 5 / 1 to 2 / 1).
[0169] The second recycling container 34 is connected to the fifth interface of the fourteenth valve 14;
[0170] The fifteenth valve 15 includes at least a first interface, a second interface, and a third interface. The fifteenth valve 15 is capable of enabling the first interface to be connected to the second interface or the first interface to be connected to the third interface. The first interface of the fifteenth valve 15 is connected to the other end of the chromatographic column assembly 31, the second interface of the fifteenth valve 15 is connected to the formulation module (the third interface of the sixteenth valve 16), and the third interface of the fifteenth valve 15 is connected to the second recovery container 34.
[0171] Preferably, the fourteenth valve 14 and the fifteenth valve 15 are both electrically controlled valves.
[0172] First, such as Figure 5 As shown, a six-way valve is provided that can achieve the function of the fourteenth valve 14 mentioned above.
[0173] Specifically, such as Figure 5 (a)~ Figure 5 As shown in (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 valve core V4. The six-way valve body V3 is provided with a first port ①, a second port ②, a third port ③, a fourth port ④, a fifth port ⑤, and a sixth port ⑥ in a counterclockwise direction. By rotating the valve core V4, the first port ① is connected to the second port ②, the third port ③ is connected to the fourth port ④, and the fifth port ⑤ is connected to the sixth port ⑥ (e.g., ...). Figure 5 (as shown in (a)), or to achieve connectivity between the second interface ② and the third interface ③, the fourth interface ④ and the fifth interface ⑤, and the sixth interface ⑥ and the first interface ① (as shown in (a)). Figure 5 (b)). In addition, based on the above-described six-way valve structure, those skilled in the art know, according to the prior art, how to control the six-way valve core V4 to rotate relative to the six-way valve body V3 by a fixed angle to achieve the electric (electromagnetic) control of the six-way valve (e.g., by setting a stepper motor to control the rotation of the valve core V4).
[0174] In addition, such as Figure 2 (a) Figure 2As shown in (b), the fifteenth valve 15 is a three-way valve that can enable the first port ① to be connected to the second port ② or the first port ① to be connected to the third port ③. This is existing technology, and the corresponding electric control valve (such as a solenoid valve) can be purchased directly on the market.
[0175] Chromatographic columns are existing technology and will not be described in detail here. The chromatographic column assembly 31 of this application is a combination of one or more existing chromatographic columns (such as multiple chromatographic columns connected in series and / or in parallel).
[0176] The specific purification process performed by the purification module can be as follows: Figure 2 (a) Figure 2 As shown in (b).
[0177] Initially, the state of the fourteenth valve 14 is as follows: Figure 2 As shown in (a), at this time, the solution of crude compound I that flows in from the reaction module enters the metering ring 32 through the fourth interface ④ and the third interface ③, and a small amount of excess solution flows into the second recovery container 34 through the sixth interface ⑥ and the fifth interface ⑤. At this time, the solution of crude compound I will remain in the metering ring 32.
[0178] Afterwards, the state of the fourteenth valve 14 is as follows: Figure 2 As shown in (b), the fifteenth valve 15 connects the first port ① and the third port ③, at which point the liquid transfer pump 33 starts working. The liquid transfer pump 33 pushes out the fluid (ethanol and water), and after the fluid flows through the first port ① and the sixth port ⑥, it carries out the solution of the crude dissolved compound I in the metering loop 32, and flows into the chromatographic column assembly 31 through the third port ③ and the second port ②, thereby performing purification.
[0179] Finally, the fifteenth valve 15 connects the first interface ① and the second interface ②, and the fluid pushed out by the liquid transfer pump 33 pushes the purified compound I product solution into the formulation module.
[0180] This embodiment provides a specific purification module. By changing the operating states of the fourteenth valve 14 and the fifteenth valve 15, and by cooperating with the liquid transfer pump 33, the crude compound I is purified to obtain the pure compound I. In particular, when all valves and the liquid transfer pump 33 are automatically controlled, the above purification process can be automated.
[0181] In one embodiment, the prescription module includes:
[0182] The sixteenth valve 16 and the seventeenth valve 17 each include at least a first interface, a second interface, and a third interface, and both the sixteenth valve and the seventeenth valve are capable of making any two of the three interfaces conductive or making all three interfaces non-conductive; wherein, the first interface of the sixteenth valve 16 is connected to the second interface of the thirteenth valve 13, the second interface of the sixteenth valve 16 is connected to the first interface of the seventeenth valve 17, the third interface of the sixteenth valve 16 is connected to the purification module (the second interface of the fifteenth valve 15) (pipeline B is connected to pipeline B'), and the second interface of the seventeenth valve 17 is connected to the third negative pressure pipeline N3;
[0183] The finished product collection container 36 is connected to the transfer container 35;
[0184] The transfer container 35 is connected to the third port of the seventeenth valve 17, the finished product collection container 36, and the fourth negative pressure pipeline N4, respectively. The transfer container 35 contains polysorbate 80(II), sodium chloride, vitamin C and sterile water for injection, for prescription purposes.
[0185] The structures of the sixteenth valve 16, the seventeenth valve 17, etc. in this embodiment have been described above and will not be repeated here.
[0186] The specific process of enrichment and prescription in the prescription module is as follows: Figure 8 (a)~ Figure 8 As shown in (b).
[0187] Initially, the states of valves 16 and 17 are as follows: Figure 8 As shown in (a), at this time, the product solution of compound I flowing out of the purification module enters the transfer container 35 for formulation.
[0188] Afterwards, the states of valves 1 through 17 are as follows: Figure 8 As shown in (b), positive pressure is introduced into the first positive pressure pipeline P1 to push the formulated compound I solution into the finished product collection container 36, thereby collecting the liquid composition of compound I. 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.
[0189] This embodiment provides a specific formulation module. By controlling the sixteenth valve 16 and the seventeenth valve 17, in conjunction with the purification module, the purified compound I is formulated and further collected to obtain a liquid composition of compound I. In particular, when the sixteenth valve 16 and the seventeenth valve 17 are automatically controlled, the above-mentioned formulation and collection can be automated.
[0190] In addition, the above technical solution includes setting up detection / monitoring equipment to detect the operation of the equipment. Specifically, this can be done by... 18 Radioactivity detectors are installed at one or more locations in the tubing between the F-ion enrichment chamber 21, the fifth reagent container 30, the twelfth valve 12, and the fourteenth valve 14 to detect radioactivity. Ultraviolet detectors and radioactivity detectors can be installed on the column assembly to determine whether to initiate the collection and purification of the mobile phase.
[0191] This embodiment provides a method for producing a liquid composition of compound I using the above-described equipment, comprising:
[0192] Use a preprocessing module to enrich 18 F ions;
[0193] Use reaction modules to enrich 18 F ions react with the precursor of compound I to generate tert-butyl ester of compound I, and then the tert-butyl ester of compound I undergoes a detert-butylation reaction to obtain crude compound I;
[0194] The crude compound I was purified using a purification module to obtain the pure compound I.
[0195] The purified compound I was formulated into a liquid composition using the formulation module.
[0196] More specific operating steps have been introduced above and will not be repeated here.
[0197] Although the embodiments of this application have been described above, this application is not limited to the specific embodiments and application fields described above. The specific embodiments described above are merely illustrative and instructive, and not restrictive. Those skilled in the art, based on the guidance of this specification and without departing from the scope of protection of the claims of this application, can make many other forms, all of which are within the scope of protection claimed in this application.
Claims
1. An apparatus for producing a liquid composition of compound I, characterized in that, include: Preprocessing module for enrichment 18 F ions; The reaction module is used to process the enriched product. 18 F ions react with the precursor of compound I to generate tert-butyl ester of compound I, and then the tert-butyl ester of compound I undergoes a detert-butylation reaction to obtain crude compound I; The purification module is used to purify the crude compound I to obtain the pure compound I. The formulation module formulates the purified compound I into a liquid composition of compound I. The preprocessing module includes: A second syringe is used to introduce a substance containing [compound I] into the apparatus for producing the liquid composition of compound I. 18 F ions oxygen [ 18 O]Eighteen Waters; Positive and negative pressure lines and liquid addition lines are provided, which respectively pass through the piston of the second syringe and extend into the second syringe; the piston of the second syringe is equipped with a core rod that drives the piston to move relative to the empty cylinder; The reaction module includes: The system comprises a seventh valve, an eighth valve, a ninth valve, a tenth valve, an eleventh valve, a twelfth valve, and a thirteenth valve. Each of the seventh to thirteenth valves includes at least a first interface, a second interface, and a third interface. Each of the seventh to thirteenth valves is capable of either having any two of its three interfaces connected or having all three interfaces deactivated. The first interface of the seventh valve 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 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 second interface of the eleventh 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. The third interface of the twelfth valve is connected to the purification module. The reaction vessel is connected to the second negative pressure pipeline and the third port of the seventh valve, respectively; the pipeline connecting the reaction vessel and the third port of the seventh valve extends to the bottom of the reaction vessel; control valves for controlling the on / off state of the pipeline are provided on the second negative pressure pipeline, the pipeline between the reaction vessel and the third port of the seventh valve. Temperature control components for heating and / or cooling the reaction vessel; The second reagent container is connected to the third port of the eighth valve; The third syringe is connected to the third port of the ninth valve; The third reagent container is connected to the third port of the tenth valve; The fourth reagent container is connected to the third port of the eleventh valve; The fifth reagent container is connected to the third interface of the thirteenth valve; The pretreatment module also includes a first positive pressure line, which is capable of providing positive pressure to the first interface of the seventh valve.
2. The device as described in claim 1, characterized in that, The preprocessing module further includes: The second linear drive device is capable of driving the piston of the second syringe to move inside the empty cylinder.
3. The device as described in claim 1, characterized in that, The reaction module further includes: The third linear drive device is capable of driving the piston of the third syringe to move inside the empty cylinder.
4. The device as described in claim 1, characterized in that, The purification module includes: 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. The fourteenth valve is switchable between a first mode and a second mode. In the first mode, the first interface is connected to the second interface, the third interface to the fourth interface, and the fifth interface to the sixth interface. In the second mode, the second interface is connected to the third interface, the fourth interface to the fifth interface, and the sixth interface to the first interface. The fourth interface of the fourteenth valve is connected to the reaction module. A chromatographic column assembly, one end of which is connected to the second interface of the fourteenth valve; A metering loop, with its two ends connected to the third port of the fourteenth valve and the sixth port of the fourteenth valve, respectively; A liquid transfer pump is 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 is capable of enabling the first interface to be connected to the second interface or the first interface to be connected to the third interface. The first interface of the fifteenth valve is connected to the other end of the chromatographic column assembly, the second interface of the fifteenth valve is connected to the formulation module, and the third interface of the fifteenth valve is connected to the second recovery container.
5. The device as described in claim 4, characterized in that, The prescription module includes: The sixteenth valve and the seventeenth valve each include at least a first interface, a second interface, and a third interface, and both the sixteenth valve and the seventeenth valve are capable of making any two of the three interfaces conductive or making all three interfaces non-conductive; 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 is connected to the third negative pressure pipeline; Finished product collection container; The transfer container is connected to the third port of the seventeenth valve, the finished product collection container, and the fourth negative pressure pipeline, respectively.
6. A method for producing a liquid composition of compound I, using the apparatus according to any one of claims 1 to 5, comprising: Use a preprocessing module to enrich 18 F ions; Use reaction modules to enrich 18 F ions react with the precursor of compound I to generate tert-butyl ester of compound I, and then the tert-butyl ester of compound I undergoes a detert-butylation reaction to obtain crude compound I; The crude compound I was purified using a purification module to obtain the pure compound I. The purified compound I was formulated into a liquid composition using the formulation module.
7. Use of the apparatus according to any one of claims 1 to 5 in the production of liquid compositions of compound I.
Citation Information
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