TWI359672B - Automatic process for synthesizing i-123-adam - Google Patents

Description

1359672 IX. Description of the Invention: [Technical Field] The present invention relates to a method for improving an I-123-ADAM automated synthesis system, and more particularly to an improvement on a system based on the original, which can greatly increase the drug flag The quality then leads to the method of routine drug supply. [Prior Art]

The I-123-ADAM serotonin transporter [2-((2-amino-4-iodophenyl)thio)benzyl] dimethyl amine, ADAM), provides single-photon emission tomography (SPECT) imaging. Because the occurrence of bipolar disorder is related to abnormal serotonin secretion in the brain, and the serotonin transporter angiography can not only observe the relationship between changes in serotonin neuronal system and depression or other psychotic diseases, but also can be used to evaluate antidepressant drugs. The efficacy and prognosis. The I-123-ADAM automated synthesis system is developed by the Institute itself. The system is composed of hardware and software. The software development system is based on the NI LabView image programming software. The synthesis steps are mainly divided into two parts. Oxidation reaction, filtration collection and sampling, and the system in addition to the synthesis step, there are pipeline cleaning, real-time monitoring, system testing and leak detection; while the hardware features include remote control operation, with software automatic reaction, The closed system and compact size, plus an additional pressure gauge and Geiger tube can instantly detect the reaction conditions, and instantly record and immediately detect the problem. However, according to the previously developed automatic synthesis system, although it can completely run a complete pharmaceutical process, the quality of the final product is not stable, and the radiochemical purity of the 1359672 drug remains excessive radioactive 23 source and radiochemical impurities. Cannot be applied to regular routine production. As shown in Figure 4, it is the schematic diagram of the original pipeline configuration of the original I-123-ADAM automated synthesis system. The original synthesis reaction and process of the M23-ADAM automated synthesis system will inject the aqueous solution containing radioactive disk into 5 The milliliter G1 was sterilized in a 5 1 reaction and mixed with the precursor SnAD AM.

Then, hydrogenated hydrogen was added as an oxidizing agent, and reacted at room temperature for 5 minutes, and then sodium hydrogen sulfite was added as a reducing agent to terminate the oxidation reaction, and then the solution was passed through a C-8 purification column (Sep_Pakc). 〇lumn) 5 2 adsorption, the filtrate is injected into a waste liquid bottle 5 3 ^ then injected with pure water to clean the C-8 purification column 5 2, the effluent is also injected into the waste bottle 5 3, and then 95 The ethanol column is charged with the purification column for $2. After the ethanol is injected into the column, it is washed back five times, and finally passed through a 0.22 micron (μUΟ〇 filter (MiUip〇reFilter) 5 4 to be collected by the main collector. The bottle is mixed with the pre-mixed physiological saline solution and vitamin C mixture. However, when performing the manual and automated synthesis system ADAM label experiment, as shown in Figure 5, the test results show that compared with As a result of manual ADAM labeling, the results of the automated synthesis system in the continuous labeling experiment can reach a certain radiochemical purity (>8G%), but it has not been able to break through the prescribed value of the drug-release purity of more than 90%. And, from the results of its analysis, the main It is caused by the radioactive M23 source located in the retention time of 2 minutes and the radiochemical impurity of 5 minutes in residence time, which limits the quality of the most drug-reducing product. Therefore, the automated synthetic system drug moth system of this stage is complete. After running the complete pharmaceutical process, but because the label yield and the purity of the drug Γ359672 are limited by the original hardware process, it is impossible to break through. Therefore, there are still some shortcomings in the use of routine drug supply. Therefore, the general practice The present invention is not in accordance with the needs of the user in actual use. SUMMARY OF THE INVENTION The main object of the present invention is to overcome the above-mentioned target yield and drug purity encountered by the prior art and to be limited by the original hardware process. Unable to break through the problem and improve the M23_ADAM automated synthesis system to provide a serotonin transporter contrast agent for brain diagnosis, not only large

The radiochemical purity of the drug can increase the final yield of the original drug, and the volume of the 50〇/〇 ethanol rinse can be used to improve the manual labeling method to achieve a substantial increase in the emission of the drug. Chemical purity. A secondary object of the present invention is to provide an automatic synthesis process for a serotonin transporter contrast agent I-123-ADAM for medical diagnosis, which enables an automatic synthetic marker system to be applied to routine radiopharmaceutical production, which can improve single drug use. Capacity and supply of more users. Another object of the present invention is to provide an automatic synthesis process for a monthly diagnostic transporter M23_ADAM for medical diagnosis, and the improved automated synthesis system enables the entire process to automatically complete the I-123-ADAM' effective reduction of pharmaceutical operators. In the experiment, the radiation dose is taken, and the unnecessary negligence during the human operation can be greatly reduced. For the purpose of improving the automated synthesis system, the method of improving the automated synthesis system is completed by the preparation process, and the column is required to be completed. The post-treatment and collection of the bottle pre-operations are followed by a post-oxidation reaction procedure, a filtration collection procedure, and a sampling procedure. First in the oxygen 6 1359672 P-1. I,. Year 1. In the month of n-day repair (more), the replacement of the page reaction procedure is to first extract the radioactive decomposing solution and inject it into the reaction bottle, then add an oxidant to carry out the oxidation reaction, and then add a reducing agent to terminate the oxidation after a reaction time. The reaction is followed by a filtration collection procedure, and the reaction solution in the reaction flask is injected into a C-8 purification column for adsorption, and the C-8 purification column is washed by adding water for injection, and then • the C is washed with 50% ethanol. -8 Purify the column, and after the flow washing, remove the C-8 purification column and install it separately to the original position before the improvement (ie, the position of the C-8 purification column shown in Figure 4 above), and then 95〇/〇 ethanol φ is injected into the C-8 purification column' and re-injected into an empty tube, and then washed back several times, then injected into a first collection bottle, and the product solution in the first collection bottle is flowed. After passing through a transition membrane, a second collection bottle is injected; finally, a sampling procedure is performed. After 95% ethanol is added and the filter membrane and the sterile collection bottle are replaced, 95% ethanol is injected into the c-8 purification column, and then injected. The first collection bottle enables the first collection bottle to be produced After this solution was passed through a filtration membrane, in a sterile collection bottle injection and in advance of the deployment of a good physiological saline and the mixture was mixed vitamin C. • [Embodiment] 4 Refer to the "Fig. 1" for a schematic diagram of the production process of the present invention. As shown in the figure: The present invention is a method for improving the i123 adam automated synthesis system, which comprises at least the following procedures and steps: Preparing the program red (A) preparing the drug U: adding hydrogen peroxide to a first drug bottle (H2〇) 2) solution, in the second drug bottle plus human sulfite gas aHS 〇 3) ' add a sodium phosphite (Na2HP03 in a third drug bottle; the fourth and fifth drug bottles are added to the water for injection (), at 7 Π59672 'w year'. The month w repair (more) is replacing the page of the sixth drug bottle with 50% ethanol (EtOH), and adding a 90% ethanol to a seventh drug bottle. The aqueous solution containing radioactive ammonium iodide Inject into a sterile reaction bottle, and introduce a reagent precursor SnADAM dissolved in ethanol into the reaction bottle with a carrier gas for mixing with the aqueous solution containing radioactive ammonium iodide; (B) C-8 purification column Pretreatment 1 2: Pre-treat a C-8 Sep-pak column, add ethanol and water for injection; Φ (c) Sterile collection bottle Pre-operation 13: Take vitamin C (

Ascorbic acid) injection and glacial acetic acid were added to 〇 9% sodium sulphate injection, mixed evenly, and extracted with a sterile syringe, injected into a sterile collection via a Millipore Millex GV filter; Oxidation reaction procedure (D The radioactive ammonium iodide solution is injected into the reaction bottle. 4: A sampling valve is rotated to the filling position, and the radioactive ammonium iodide solution is filled into the sampling loop by nitrogen pressure, and the filled liquid flows to a recovery bottle. After the impurity, the radioactive ammonium iodide solution in the sampling loop is immersed in the reaction bottle under nitrogen pressure, and stirred by a bubble formed by nitrogen pressure, wherein the gas system in the reaction bottle is made of a soda lime (s〇dalime) (E) injecting the oxidizing agent 1 5: injecting the hydrogen peroxide solution of the first pharmaceutical bottle as an oxidizing agent into the reaction flask, stirring at room temperature with a bubble to a reaction time; (F) injecting a reducing agent i 6 : The sodium bisulphite of the second drug bottle and the saturated sodium phosphite of the third drug bottle are used as a reducing agent, and the anti- 8 1359672 is injected into the _:_ ' k temple Μ月N日修(more) replacement Page _ _ 〇 瓶 bottle ' and use the bubble to stir to the reaction time, terminate the oxidation reaction; Filter collection procedure (G) reaction solution into the C-8 purification column adsorption 17: Inject the reaction solution into the reaction bottle The C-8 purification column is adsorbed, and the filtrate is directly injected into a waste liquid bottle; (Η) injecting water for injection to clean the c-8 purification column 18: injecting the fourth medicine bottle into the reaction bottle, The reaction liquid φ in the reaction flask is injected into the C-8 purification column. The filtrate is directly injected into the waste bottle, and then directly injected into the C-8 purification column with the injection water of the fifth drug bottle, and the discharged filtrate is directly injected into the waste bottle; Injecting 50% ethanol to wash the C-8 purification column 19. Injecting the 50% ethanol of the sixth drug bottle directly into the C-8 purification column, the effluent filtrate is directly injected into the waste bottle, and then removed. The C-8 purification column was separately installed to the original position before the improvement (ie, the position of the C-8 purification column shown in Figure 4 above); (J) 95% ethanol was injected to reflux the C-8 purification. Column 2 〇: 95% ethanol of the seventh drug bottle is injected into the C-8 purification column by nitrogen pressure, and then injected into an empty tube, and then washed back several times; (Κ) collected and filtered to collect Bottle 2 1 : Finally injected into a first collection bottle, and the product solution in the first collection bottle is passed through a filter, membrane, and then injected into a second collection bottle; sampling procedure (L) is supplemented with 95% ethanol and replaced by filtration Membrane and sterile collection bottle 2 1359672 f, supplement the 95% ethanol of the seventh drug bottle, replace the filter cartridge and replace the first collection瓿Step (c) sterile collection bottle; and (Μ) inject 95% ethanol to C_8 purification column, collect and filter to sterile collection bottle 2 3: inject 95 〇/〇 ethanol of the seventh drug bottle under nitrogen pressure C-8 purification of the column, and then injecting the first collection bottle, so that the product solution in the first collection bottle flows through the filtration membrane, and then injected into the aseptic collection bottle and mixed with the pre-mixed physiological saline and vitamin C mixture. Referring to FIG. 2, it is a schematic diagram of the configuration of the pipeline of the present invention. As shown in the figure, when the present invention is operated, in a preferred embodiment, at least the following procedures and steps are included: The preparation procedure (A 1 ) is performed by adding a nitrogen oxide solution to the first drug bottle 3, adding sodium hydrogen sulfite to a second drug bottle 3 2, and adding sodium phosphite to a third drug bottle 3 3 . The fourth and fifth drug bottles 3 4, 3 5 are each added with water for injection, 5 % ethanol is added to a sixth drug bottle 36, and 90 ° / is added to a seventh drug bottle 37. Ethanol. And injecting an aqueous solution containing radioactive ammonium iodide into a 5 ml (mI) sterile reaction flask 38, and dissolving 4 μίί (μ1) of the carrier gas-potassium iodide (ΚΙ) with a microgram of Ug) The ethanol precursor SnADAM is introduced into the reaction flask 38 for mixing with the aqueous solution containing radioactive ammonium iodide; (13 1) p-. 8 Purification column 39 is pretreated, added with 1 ml of ethanol and 5 ml of water for injection; (C 1 ) 75 μl of vitamin C injection and 15 μl of glacial vinegar 1359672 acid is added to 20 ml of 0.9% sodium chloride injection. The liquid was 'mixed evenly, and 5.5 ml was extracted with a sterile syringe, and filtered through a Millip〇re Mi丨丨e>i GV 0.22 micron (μπι) filter into a G2 blue-free collection bottle 4 〇b; oxidation reaction procedure

(D 1 ) Open the C13 connector 'Rotate a 6 V 1 3 sampling valve to the filling position and open the Cl2, (8) and C19 joints' to volume 0.3 ml of the radioactive ammonium iodide solution via 乂9 And the V12 control valve is filled into the L〇〇p sampling loop, and the filled liquid flows from the ...3 control valve to the recovery bottle 4i, where the c]8 joint remains open until the end. After filling for 3 seconds, the C12 is closed. And the ci3 joint, and open the C9 and C2 〇 joints, using the gas pressure to inject the radioactive ammonium hydride solution in the Loop sampling loop into the counter bank 3 8 via the V2Q control valve, and within the reaction bottle 38 The gas is discharged through a normally open control valve and a soda lime tube 4 2 containing sodium hydroxide (Na〇H) particles. After 5 seconds, the _ C9, C19 and (3) joints are opened and the force is formed. After the bubble is searched off for 1 〇 second, turn off /,,, fill the radioactive Wei ammonium solution (4) Nitrogen system 2: (Needle Va丨ve) adjust the appropriate flow rate, make the solution slow, and fill the Loop sampling loop, ^ ^ 1) Open the CI connector, turn the first drug bottle 3 1 into the sputum, the combined solution as the oxidant, azole 8, and close the C1 after 5 seconds. Connector: valve into the reaction plate 3 under the use of air bubbles for stirring 5 eight " sub-open C〗 4 joint 'at room temperature into the 仃 f see mixing for 5 minutes after closing ci; mouth bottle St second drug bottle 32 of sulfurous acid Nitrogen and the third drug... 3 of Weiner as a reducing agent. First open the C2 connector, Γ359672. Inject the sodium bisulfite into the reaction vial via the V2 control valve. After 8 seconds, close the C2 connector and open the C14 connector. Stir for 10 seconds with air bubbles, then close the C14 connector and then turn it on. C3 joint, the saturated sodium phosphite is injected into the reaction vial via the V3 control valve for 3,8,5 seconds, then the C3 joint is closed and the c 14 joint is opened, and the bubble is used. • After stirring for 5 minutes, the C14 joint is closed to terminate the oxidation reaction. ; Filter collection procedure (G 1 ) to open C3, C8 (close V8 control valve) and Cl 5 connector 'Inject the reaction solution in the reaction flask 38 into the C-8 purification column through V14a and v 1 5 control valve 3 9 Adsorption, the filtrate flowing out between them is directly injected into a waste liquid bottle 4 3 ; ' (Η 1 ) opens the C4 joint, and injects the fourth medicine bottle 34 4 into the reaction bottle 3 8 via the V4 control valve and opens the C3 , C8 (close the V8 control valve) and C! 5 joint, so that the reaction liquid in the reaction flask 38 is injected into the C_8 purification column 3 9 through the V14a and V15 control valves, and the filtrate flowing out therefrom is directly injected into the waste liquid bottle. 4 3, and close the C8 and C i 5 connectors after % 60 ^ less. After the final product is adsorbed on the c_8 purification column 39, the C5 linker is opened and the C14 linker is closed, and the fifth version of the 35 water for injection is directly injected into the C-8 purification column via a v 5 control valve in 1 μl of water. 3 9 to wash out the 丨 丨 23 source on the unmarked, the filtrate flowing out of it is also directly injected into the waste bottle 4 3, and close the C5 joint after 300 seconds; > (I 1 ) open C6 The joint 'the sixth drug bottle 3 65% ethanol was directly injected into the c_8 purification column 3 9 as a gradient concentration through the V6 control valve to remove other impurities, and the flow of the 12 1359672 effluent was also directly Inject the waste bottle 4 3 ' and close the C6 joint after 3 sec., then remove the C-8 purification tube 桎 3 9 and install it separately to the position after the v 16 control valve; 1) Open the joints such as C7, C10 and C16, and inject the 95% ethanol of the seventh drug bottle 37 into the C-8 purification column 3 through the V7 and Vl6b control valves by nitrogen pressure and control the valve via vl〇b = Enter an empty tube 4 4, close the C16 joint after about 30 seconds, and open the U7 joint, so that the ethanol in the empty tube 4 4 flows back in reverse, and then close C1 after 30 seconds. 7 joint, and open the Cl6 joint, so that the ethanol in the c_8 purification column 3 9 is re-flowed to the empty tube 4 4, repeated for reflux washing a total of 10 times; '(K 1 ) to the above steps (J丄After the third pass, the c ^ 7 f cio connector is closed, and the C11 and C16 connectors are opened, so that the ethanol solution of the 〇8 purified s column 3 9 is injected into a first collection bottle via v丨0a and v丨丨b. 4 5, after 30 seconds, close the joints C7, (3) and C16, and open the C21 joint 'to make the product solution in the first collection bottle 45 flow through the filter membrane 46a, then inject the second collection bottle 4〇a, After 8 seconds, the C18 and C21 joints were closed 'by the end to precipitate the final wadadam product; the sampling procedure YL 1 ) supplemented the seventh drug bottle 37 75% ethanol 0.9 ml 'Asia replacement core 4 6 b and replaced the second collection bottle 4 qa is the step (C 1 ) aseptic collection bottle 4 〇b; and —"(M 1 ) opens the joints such as C7, C1, C16 and C18, and uses nitrogen to force the seventh drug bottle 37% of 90% ethanol via The V7 and VI 6b control valves are injected into the C-8 purification column 3 9, and then injected into the first collection bottle 4 via VI〇a and VI lb, and the C7, c丨丨 and C16 connectors are closed after 30 seconds. And the C21 joint is opened, and the product solution in the first collection bottle 45 is passed through the filter membrane 46b, and then injected into the sterile collection bottle 40b and mixed with the pre-mixed physiological saline and vitamin C mixture. Turn off the C18 and C21 connectors after 60 seconds. It can be seen from the above that the present invention removes the pipeline originally through the vu control valve, and installs a c_8 purified tubular filter line at the V5 control valve to guide the transition line to the waste> night bottle to eliminate waste; The C-8 purification column of the reaction product will be washed in advance with 丨〇ml of water for injection in the newly added filter unit, and the waste liquid washed by 5G% of ethanol can still be eliminated to the waste along the same path. In the liquid bottle, after completing the injection of dihydrate and 50% B flow washing procedure, the purification pipe column should be separately placed to the position after the original control valve, # V16 control valve, after operation ^ 7 , separately with 95% ethanol The action of back and forth extraction is carried out, and after the back extraction is owed, the final product is sent to the collection bottle by nitrogen gas for collection. Analysis of the results. As shown in the figure: After the modification of the automatic synthesizing system, the system labeling experiment is carried out by the automatic synthesis system in the figure. The figure is shown in the “Graph 3” in May.

Shown: M23_ADAM using the above method

Γ359672 8%, 38.0% and 36.6% ‘average 37.1%. From the data results, it can be seen that the radiochemical purity of the automatic synthesis system is 94.3% on average, and the radiochemical purity is 93.6% higher than that of the manual label, and the average yield of the automatic synthesis system is 37.2% higher than the average of 47.2%. The radiochemical purity of the manual label is 37.1%. Therefore, the modification of the improved method of the present invention can greatly improve the availability of the drug.

In addition, the modified automatic synthesis system of the present invention also performs a labeling experiment by increasing the flow volume of 50 〇/〇 ethanol, and the analysis results obtained therefrom can significantly reduce the proportion of radiochemical impurities. It can be seen from the above that the present invention can increase the final chemical yield of the original drug in addition to greatly improving the radiochemical purity of the drug, and the method for improving the manual label can be more effectively used after increasing the volume of the 50% ethanol flow washing. In order to achieve a significant increase in the radiochemical purity of the drug, the application of the self-image system to routine radiopharmaceutical production can increase the capacity of single-attack drugs and supply more users, and the whole process (4)

= In addition to avoiding unnecessary radiation during the experiment, it can significantly reduce the unnecessary negligence of human operation. In summary, the present invention is an improved M23_adam automation: system-based method, which can effectively improve various shortcomings of the conventional use, and utilizes the original automated synthesis system for internal pipeline modification, which can not only greatly reduce the proportion of eyebrow purity, but also greatly After extracting the volume of ethanol, it can greatly reduce the ratio of η to radiochemical impurities, so as to further increase the original 纟 纟 pure

By: (d) the use of automated synthesis systems into the real J significantly reduced the operator's acceptance of the dose, in order to improve the final production of the product 15 1359672 and radiochemical purity to increase the availability of drugs while ensuring the quality of drugs and provide sustainable development services, Further, the invention can be made more progressive, more practical, and more suitable for the user to meet the requirements of the invention patent application, and the patent application is filed according to law. The above is only the preferred embodiment of the present invention, and the scope of the present invention is not limited thereto; therefore, the simple equivalent change made according to the scope of the present invention and the contents of the invention description And the modifications 'should be within the scope of the invention patent.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic view showing the production process of the present invention. Fig. 2 is a schematic view showing the arrangement of the marker tube of the present invention. Fig. 3 is a schematic view showing the results of analysis of the pipeline before and after the modification of the present invention. Figure 4 is a schematic diagram of the standard pipeline configuration of the original M23-ADAM automated synthesis system.

Figure 5 is a schematic diagram of the experimental results of the manual and original automated synthesis system ADAM. [Description of main component symbols] (part of the invention) Steps (A) to (M) 11 to 23 First drug bottle 3 1 Second drug bottle 3 2 Third drug bottle 3 3 Fourth drug bottle 3 4 Fifth drug bottle 3 5 16 1359672 Sixth drug bottle 3 6 Seventh drug bottle 3 7 Reaction bottle 3 8 C-8 purification column 3 9 Second collection bottle 4 0 a Aseptic collection bottle 4 0 b Recovery bottle 4 1 Soda lime tube 4 2 Waste bottle 4 3 Empty tube 4 4 First collection bottle 4 5 Over 遽, membrane 4 6a, 4 6b Sampling loop Loop Cl~C21 joint VI~V21 control valve (customized part)

Reaction bottle 5 1 C-8 purification column 5 2 waste bottle 5 3 filter membrane 5 4 collection bottle 5 5

Claims (1)

13*59672 X. Patent application scope: • A method for improving the 123-ADAM automated synthesis system, which includes at least the following procedures and steps: Preparation procedure (A) adding hydrogen peroxide (Η2〇2) to each of the first drug bottles, adding sodium hydrogen sulfite (NaHs〇3) to a second drug bottle, and adding sodium phosphite to a third drug bottle ( Na2HP〇3), adding water for injection (AO) to each of the fourth and fifth drug bottles, adding 50% ethanol (EtOH) to a sixth drug bottle, and adding 90% ethanol to a seventh drug bottle, and An aqueous solution containing radioactive ammonium iodide is injected into the reaction flask, and a gas-soluble molybdenum molybdenum SnADAM is introduced into the reaction bottle with a carrier gas for mixing with the aqueous solution containing radioactive ammonium iodide; B) pre-treating a C-8 Pur-column column (C-8 Sep-pak column), adding ethanol and washing water for injection; β啐ί. "I day repair (more) replacement page (C) Take vitamin C (Injection) and glacial acetic acid into a 0.9% sodium sulphate injection, mix it evenly and extract it with a sterile syringe, and inject it through a MiMipore Millex GV filter. Collecting the bottle; Oxidation reaction procedure (D) Rotating a sampling valve to the filling position, filling the radioactive ammonium iodide solution into the sampling loop by nitrogen pressure, and flowing the liquid to a recovery bottle, followed by nitrogen pressure The radioactive ammonium iodide solution in the sampling loop is injected into the reaction flask and stirred by a bubble formed by nitrogen pressure. The gas system in the reaction flask is discharged from a base 18 Γ 359672 lime (Sodalime) tube; (E) The hydrogen peroxide solution of the first drug bottle is injected into the reaction bottle as an oxidant, and stirred at room temperature with a bubble until the reaction takes time; (F) the first drug bottle of sodium arsenite and the third drug bottle Saturating sodium phosphite as a reducing agent, injecting the reaction flask, and stirring with a bubble to the time required for the reaction, terminating the oxidation reaction; (G) flowing the reaction liquid in the reaction flask through the c_8 purification column, and the filtrate flowing out during the process is directly injected into a waste liquid bottle; (Η)/the main injection water of the fourth medicine bottle is sent to the reaction bottle, so that The reaction liquid in the reaction bottle is injected into the C-8 purification column, and the effluent flowing out of the reaction bottle is directly injected into the waste liquid bottle, and then directly injected into the C-8 purification tube column with the medicinal water of the fifth medicine bottle. Cleaning, during which the filtrate flowing out is also directly injected into the waste bottle; (I) directly injecting the 50% ethanol of the sixth drug bottle into the c-8 hydrazine column, and the liquid is directly injected into the waste liquid, and then removing the C-8 purification column and separately Installed to the original position before the improvement; (J) Inject the 95% ethanol of the seventh drug bottle into the C-8 purification column by nitrogen pressure, and then inject an empty tube, and then carry out the reflux washing several times; Finally, injecting into a first collection bottle 'and passing the product solution in the first collection bottle through a filter membrane' into a second collection bottle; ', 19 Γ 359672 sampling procedure (L) supplementing the seventh drug bottle 95 % ethanol, and replacing the filter membrane and replacing the second collection bottle as the step (C) sterile collection bottle; and (Μ) injecting 9〇% ethanol of the seventh drug bottle into the C-8 purification column under nitrogen pressure, and then injecting The first collection bottle allows the product solution in the first collection bottle to flow through the filter membrane, and then is injected into a sterile collection bottle and mixed with a pre-mixed physiological saline solution and a vitamin C mixture. 2. A method of improving an M23-ADAM automated synthesis system according to claim 1, wherein the carrier gas system is potassium iodide (ΚΙ). 3 According to the improvement of the patent scope of the patent range 1, the automatic μ123_Α[) ΑΜ automated, systemic method, in which the nitrogen gas system in the oxidation reaction process is adjusted by a needle valve (Needle Valve). 4 The method for improving the M23_ADAM automated synthesis system according to the first aspect of the patent scope of the invention, wherein the filling time of the step (D) of the radioactive moth money solution is 3 seconds. According to the method of the U123-ADAM automated synthesis system described in the first paragraph of the patent scope of the May, wherein the step (D) I gas agitation time is seconds. The method of improving the Bu-123-ADAM automated synthesis system according to the first aspect of the patent application, wherein the stirring time of the 7 is 5 minutes. According to the method for improving the M23-ADAM dynamic synthesis system described in the first aspect of the patent scope of the fifth aspect, wherein the step (F) nitrogen 20 is mixed for 10 seconds. The method of improving the Bu 1 23-ADAM automated synthesis system according to the first aspect of the patent application, wherein the step (G) nitrogen stirring time is 5 minutes. The method of improving the Bu-123-ADAM automated synthesis system according to the first aspect of the patent application, wherein the step (Κ) is performed a total of 10 times for reflux washing. 'Improved according to the scope of claim 1 of the patent application _ 23_ADAM automated synthesis system method, wherein the yield of synthetic label obtained by fully automatic operation is 47.2% on average, and I-1 23ΆDAM ^ -+Λ* /u ja Λ-ι- ώ: τ seat. . The radiochemical purity averaged 94.3 〇 / 0.