CN107474082A - Double batch PET developers18F FDG pharmaceutical synthesis device and method - Google Patents

Double batch PET developers18F FDG pharmaceutical synthesis device and method Download PDF

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CN107474082A
CN107474082A CN201710687609.4A CN201710687609A CN107474082A CN 107474082 A CN107474082 A CN 107474082A CN 201710687609 A CN201710687609 A CN 201710687609A CN 107474082 A CN107474082 A CN 107474082A
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synthesis
unit
fdg
reaction
solution
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CN107474082B (en
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陈立光
雷震山
邓庆荣
李瑜
梁明泉
陈新亮
周必强
吕光华
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Shenzhen Health Committee Office
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
    • C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0006—Controlling or regulating processes
    • B01J19/0013—Controlling the temperature of the process
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/24—Stationary reactors without moving elements inside
    • B01J19/2415—Tubular reactors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J4/00—Feed or outlet devices; Feed or outlet control devices
    • B01J4/001—Feed or outlet devices as such, e.g. feeding tubes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/005—Sugars; Derivatives thereof; Nucleosides; Nucleotides; Nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00049—Controlling or regulating processes
    • B01J2219/00051—Controlling the temperature
    • B01J2219/00054—Controlling or regulating the heat exchange system
    • B01J2219/00056—Controlling or regulating the heat exchange system involving measured parameters
    • B01J2219/00058—Temperature measurement
    • B01J2219/0006—Temperature measurement of the heat exchange medium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00049—Controlling or regulating processes
    • B01J2219/00051—Controlling the temperature
    • B01J2219/00074—Controlling the temperature by indirect heating or cooling employing heat exchange fluids
    • B01J2219/00087—Controlling the temperature by indirect heating or cooling employing heat exchange fluids with heat exchange elements outside the reactor
    • B01J2219/00103—Controlling the temperature by indirect heating or cooling employing heat exchange fluids with heat exchange elements outside the reactor in a heat exchanger separate from the reactor
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled

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  • Optics & Photonics (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
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Abstract

The present invention provides a kind of double batch PET developers18F FDG pharmaceutical synthesis equipment, including：The shunting selecting module of the nucleic of F 18 and double batch synthesis modules；Double batch synthesis modules include two sets of synthesis modules of binary channel design；The synthesis module includes：The anion processing units of F 18,18The recyclable unit of O heavy-oxygen-enriched waters, automatic sample unit, reaction member, heating unit, malleation transmission unit and cold-hot wind cycling element.Combined coefficient is stable, synthetic effect can realize well and simultaneously that double batches of acid and alkali hydrolysis hydrolyze.

Description

Double batch PET developers18F-FDG pharmaceutical synthesis device and method
Technical field
The present invention relates to positron radiopharmaceuticals synthesis technical field in nuclear pharmacology, more particularly to double batch PET Developer18F-FDG pharmaceutical synthesis device and method.
Background technology
PET/CT imagings have turned into new " bright spot " of nuclear medicine development,18F marks18F-FDG are considered this generation Record of great value radiopharmaceutical, but from18F anions synthesize18F-FDG must be developed by calculating the full-automatic of manipulation Synthesis module.Due to18F anions belong to positive electricity subclass radionuclide, and positron annihilation occurs when being acted on material and discharges It is 511Kev to go out two energy, and direction is 180 ° of energetic gamma rays, so from18F anions synthesize18F-FDG must be researched and developed Go out by calculating the full-automatic synthesis module of manipulation, and synthesizer is positioned in the protective shielding hot cell for possess requirement and carried out.From Successfully synthesized from issues such as Hamacher K in 198618Since F-FDG, external many cyclotron centers are added to this one after another The research and development field of medicine.Until the Mock BH of CTI companies of the U.S. in 1996 develop global first generation commercialization18F-FDG is synthesized Module CPCU, subsequent GE companies also announce the research and development success of Tracerlab FX-FDG synthesis modules.In the last thirty years, it is external18The research and development of F-FDG synthesis module and production technology relative maturity, but the equipment for not realizing acid and alkali hydrolysis simultaneously；In recent years Come domestic Ye You mechanisms to take up to be engaged in18The R＆D work of F-FDG synthesis module, also achieve some achievements.Beijing 301 Hospital's Zhang Jinming and Tian Jiahe etc. also develop the-FDG model synthesis modules of PET- II for 2003.The synthesis module belongs to single batch Secondary synthesis, the shortcomings of mode of heating uses aluminium ingot eddy heating for heating mode unstable and causes combined coefficient unstable be present.Simultaneously Country will18F-FDG's includes《Chinese Pharmacopoeia 2015 editions》Afterwards ,-FDG models the synthesis modules of PET- II are using the final production of negative pressure transmission The technological process of product does not meet the standard requirement of ten thousand grades of producing region cleanliness factor.Also there are double batch synthesis, but be designed with Very big technological deficiency, so as to cause the uncertainty into synthesis module nucleic quantity.
So currently without a kind of combined coefficient is stable, synthetic effect can realize well and simultaneously double batches of acid and alkali hydrolysis Equipment.
The content of the invention
The present invention is in order to solve in the prior art without a kind of combined coefficient is stable, synthetic effect can realize well and simultaneously acid A kind of the problem of double batch equipments of basic hydrolysis, there is provided double batch PET developers18F-FDG pharmaceutical synthesis device and method.
In order to solve the above problems, the technical solution adopted by the present invention is as described below：
A kind of double batch PET developers18F-FDG pharmaceutical synthesis equipment, including：The shunting selecting module of F-18 nucleic and double Batch synthesis module；Double batch synthesis modules include two sets of synthesis modules of binary channel design；The synthesis module includes： F-18 anion processing units,18The recyclable unit of O- heavy-oxygen-enriched waters, automatic sample unit, reaction member, heating unit, malleation pass Defeated unit and cold-hot wind cycling element, cold-hot wind cycling element；The shunting selecting module of the F-18 nucleic respectively with two sets The F-18 anion processing units of synthesis module are connected；The F-18 anions processing unit respectively with it is described18O- heavy-oxygen-enriched waters can Recovery unit is connected with automatic sample unit；The automatic sample unit is joined directly together with the reaction member or born by F-18 Ion processing unit is connected with the reaction member, and the reaction member is single with the heating unit and malleation transmission respectively Member is connected, and the cold-hot wind cycling element covers on reaction member, heating unit and transparent window together.
Preferably, two sets of synthesis modules are sour water solution synthesis model；Or it is basic hydrolysis synthesis model；Or on one side For sour water solution synthesis model, another side is basic hydrolysis synthesis model.
Preferably, being set between the shunting selecting module of the F-18 nucleic and the F-18 anions processing unit to cut The electronic three-way valve for changing path realizes that nucleic shunts.
Preferably, the malleation transmission unit includes malleation transmission air valve and mechanical pressure-reducing valve, using 60-80Psi's Decoction is transmitted out by nitrogen.
Preferably, the QMA trapping columns capture F-18 anions of the F-18 anions processing unit, the automatic sample list The catalyst solution of member elutes release F-18 anions via QMA trapping columns and is sent to the reaction member.
Preferably, the reaction member includes reaction vessel and reaction vessel support；The reaction vessel includes container master Body and capillary, the one end open of the capillary are arranged in the side wall of the openend of the container body, by with opening The sealing ring closing or drainage of mouth；Another end opening of the capillary leads to the bottom of the container body；Reaction vessel Reaction vessel is fixed on the reaction vessel support by support, including two seals circle, sealing ring；Carried on the sealing ring Opening, the open at one end docked with the capillary apertures in the reaction vessel side wall, and the other end is plugged into catheter or air guide Pipe.
Preferably,18The recyclable unit of O- heavy-oxygen-enriched waters will by triple valve18The collecting of O- heavy-oxygen-enriched waters and light water point Open.
Preferably, transparent window is set on the cold-hot wind cycling element.
The present invention also provides a kind of double batch PET developers18F-FDG pharmaceutical synthesis methods, K2.2.2Solution/K2CO3Catalysis The preparation method of agent solution includes：S1：Prepare K2CO3Solution：60mg K2CO3It is dissolved in 3.0ml high purity waters；S2：Prepare K2.2.2Solution：200mg K2.2.2It is dissolved in 17.0ml anhydrous acetonitriles；S3：By the K of preparation2CO3Solution and K2.2.2Solution is abundant Mixing, refrigeration are stand-by.
Preferably, reaction member adds the 0.50-1.50N of concentration hydrochloric acid；When selecting basic hydrolysis pattern, reaction member Add the 0.20-0.50N of concentration NaOH solution.
Beneficial effects of the present invention are：A kind of double batch PET developers are provided18F-FDG pharmaceutical synthesis equipment, combined coefficient Stable, synthetic effect can realize well and simultaneously that double batches of acid and alkali hydrolysis hydrolyze.
Brief description of the drawings
Fig. 1 is double batch PET developers in the embodiment of the present invention 118F-FDG pharmaceutical synthesis device structure schematic diagrams.
Fig. 2 is double batch PET developers in the embodiment of the present invention 118F-FDG pharmaceutical synthesis schematic devices.
Fig. 3 is double batch PET developers in the embodiment of the present invention 118F-FDG drug synthetic reaction cellular construction schematic diagrams.
Fig. 4 is double batch PET developers in the embodiment of the present invention 118F-FDG pharmaceutical synthesis cold-hot wind cycling element structures are shown It is intended to.
Wherein, the shunting selecting module of 1-F-18 nucleic, 2-F-18 anion processing units, 3-18O- heavy-oxygen-enriched waters are recyclable Unit, 4- automatic sample units, 5- reaction members, 6- heating units, 7- malleation transmission units, 8- cold-hot wind cycling elements, 9- Collection of products unit, 10- electronic three-way valves (V6), 11-QMA trapping columns, 12- electronic three-way valves (V9), the oxygen-enriched Water Sproadings of 13- Bottle, 14- waste liquid bottles, 15- serum bottles, 16- reaction tubes, 17- reaction pipe holders, 18- plug pipelines, 19- reaction tube main bodys, 20- Capillary, 21- sealing rings, 22- malleations transmission air valve, the mechanical pressure-reducing valves of 23-, 24- high pressure pure nitrogen gas, 25- air heaters, 26- exhaust fans, 27- transparent windows.
Embodiment
The present invention is described in detail by specific embodiment below in conjunction with the accompanying drawings, for a better understanding of this hair It is bright, but following embodiments are not intended to limit the scope of the invention.In addition, it is necessary to illustrate, the diagram provided in following embodiments Only illustrate the basic conception of the present invention in a schematic way, the component relevant with the present invention is only shown in accompanying drawing rather than according to reality Component count, shape during implementation and size are drawn, it is actual when implementing shape, quantity and the ratio of each component can be one kind with The change of meaning, and its assembly layout form may also be increasingly complex.
Embodiment 1
As depicted in figs. 1 and 2, double batch PET developers18F-FDG pharmaceutical synthesis equipment, including：The shunting of F-18 nucleic Selecting module 1 and double batch synthesis modules；
Double batch synthesis modules include two sets of synthesis modules of binary channel design；
The synthesis module includes：F-18 anions processing unit 2,18The recyclable unit 3 of O- heavy-oxygen-enriched waters, automatic sample list Member 4, reaction member 5, heating unit 6, malleation transmission unit 7 and cold-hot wind cycling element 8.
F-18 anion processing unit 2 of the shunting selecting module 1 of F-18 nucleic respectively with two sets of synthesis modules is connected；Institute State F-18 anions processing unit 2 respectively with it is described18The recyclable unit 3 of O- heavy-oxygen-enriched waters is connected with automatic sample unit 4；It is described from Dynamic sample-adding unit 4 is joined directly together with the reaction member 5 or by F-18 anions processing unit 2 and the phase of reaction member 5 Even, the reaction member 5 is connected with the heating unit 6 and the malleation transmission unit 7 respectively, the cold-hot wind cycling element 8 reaction members 5 and heating unit 6 cover on together.
In the alternative embodiments of the present invention, in addition to collection of products unit 9, for filtering and collecting synthetic product.
Double batch synthesis modules can be realized18The binary channel design of F-FDG synthesis, is equal to two sets of single batch synthesis modules, Double batches can be gradually completed by use demand18F-FDG production.Due to its completely self-contained binary channel, therefore between every batch Production is independent of each other, and can finish in first batch of synthesis while be produced into second lot medicine；Without operation between two batches time production The program of any cleaning reaction tube, pipe-line system, Simple filter post etc., so as to which the combined coefficient between batch will not be caused gradually Reduce.A kind of technique and module (application number for synthesizing Value linear radiopharmaceutical twice in succession：20150434051.X) disclose " very big technological deficiency is designed with using what two groups of leacheates eluted QMA " respectively at twice, is closed twice in succession although realizing Into, but because two groups of leacheates (while in accordance with different proportion) elution QMA is difficult to hold elution and for the first time respectively at twice The nucleic allocation proportion of secondary elution, so as to cause the uncertainty into synthesis module nucleic quantity.It is of the invention and above-mentioned set In respect of the difference of essence, set between the shunting selecting module of F-18 nucleic and the F-18 anions processing unit changeable Electronic three-way valve 10 (i.e. V6) nucleic shunting of path, radionuclide F-18 are captureed by two independent ion QMA respectively on request Post 11 is obtained, and is eluted and is discharged into specified reaction system (Residual dose is less than 3%) respectively by two bottles of independent catalyst solutions.
The shunting selecting module of F-18 nucleic is included in cyclotron F-18 target bodys (containing transfer line) and capture F-18 The design and installation of QMA trapping columns 11 of anion triple valve V6, pinch valve V6 is automatic silent to the right pattern normal open state under normality Recognize the QMA trapping columns software systems selection left side synthesis model that F-18 anions are transferred to the right prepackage, system automatically will Pinch valve V6 is switched to corresponding working state, and F-18 anions are automatically transferred in the QMA of left side prepackage；It is achieved thereby that F-18 Left and right shunts the function of selection to nucleic on demand, and synthetic reaction is provided for pair batch PET developer 18F-FDG pharmaceutical synthesis Nucleic raw material basis.
The pipe such as two four-way pinch valve V7 and V8 of module mounting design and the silica gel of connection, Teflon (Teflon) pipe Road, when V7 and V8 is in normal open state simultaneously, the liquid phase of heavy-oxygen-enriched water or O-16 water with F-18 anions is from accelerator F- 18 target bodys (containing transfer line) are successively via V6, V7, QMA trapping column 11, V8 arrival heavy-oxygen-enriched waters returnable bottle 13 or waste liquid bottle 14 Peripheral passage, realize F-18 anions and captured by QMA；When V7 and V8 is in normally off, 0.8ml K simultaneously2.2.2Solution/ K2CO3Catalyst solution realizes F- from first bottle successively reaction tube into V8, QMA trapping column 11, V7 and reaction member 5 18 anions reach the purpose of elution release F-18 nucleic from QMA to the peripheral passage for importing reaction tube.
The labelled nuclide F-18 that reaction member utilizes is to bombard target material by medical cyclotron：18The oxygen-enriched aquatic products of O- It is raw, nature water mainly with16Existing for the isotope form of O- water；18O- heavy-oxygen-enriched waters are low in the isotope abundance of nature In ten a ten thousandths,18The acquisition of O- heavy-oxygen-enriched waters is mainly held high by repeatedly multistage complicated mechanical centrifugal and enrichment method, price It is expensive, up to 3000 yuans during the price highest of every gram of heavy-oxygen-enriched water of in the market.18The recyclable unit of O- heavy-oxygen-enriched waters passes through triple valve 12 (i.e. V9) will18The collecting of O- heavy-oxygen-enriched waters and light water separates.An electricity is provided with behind F-18 anion processing units Sub- three-way valve V9, different phase is carried by F-18 anions by program controlled mode18O- heavy-oxygen-enriched waters and rinse targets it is general The collecting of water flowing separates.By the recovery system,18The rate of recovery of O- heavy-oxygen-enriched waters more than 85%,18The same position of O- heavy-oxygen-enriched waters Plain abundance is more than 90%；Reach the requirement of recycling, greatly save the financial cost of pharmaceutical synthesis.
Automatic sample unit 4 is by five serum bottles 15 that formula decoction is pre-installed on request (blood of V1, V2, V3, V4 control Clear bottle is 5 liters, V5 controls for 10 milliliters), six electromagnetic valves of V0, V1, V2, V3, V4, V5, the tracheae being connected and liquid phase (tracheae and formula decoction being wherein connected are not directly contacted with pipeline, and the teflon pipe of liquid phase pipeline needs to be inserted into serum bottle Bottom) etc. composition.Six electromagnetic valves (time of unlatching can adjust in programming) can be automatically turned on according to program, Formula decoction will accordingly be pre-installed and be transferred to the corresponding synthesis step of participation in the reaction tube of reaction member by the sequencing of program Suddenly.
Wherein V0 is opened, and by band side wall capillary reaction pipe 16 in reaction member, tube reaction is not in different height Physical location can neatly provide the function of system mixing for reaction solution.Due to18F-FDG synthesis is whole with radiation Property, the system realizes the programme-controlled full-automatic sample-adding of formula decoction and mixing, avoid human hand intervention and cause operator by Unnecessary radiation dosage damages.
As shown in figure 3, reaction member is mainly comprising the reaction tube 16 with side wall capillary of the invention specially researched and developed, reaction Pipe holder 17 and plug pipeline 18 etc., the unit causes being pipetted by program control program of five bottles of reaction solutions, the constant temperature of reaction system adds The flows such as heat, cooling, mixing, azeotropic vaporization, acid and alkali hydrolysis, drug delivery are able to integrated real in a special containment system It is existing；Realizing decoction reaction system especially by the crystal reaction tube with side wall capillary follows program to lift, in difference The mixing of system is not required to achieve the goal by other extra pipelines and mixing equipment can during height.
Reaction tube 16 includes reaction tube main body 19 and capillary 20, and the one end open of the capillary 20 is arranged on the hair In the side wall of the openend of tubule main body 19, close or drain by the sealing ring 21 with opening；The capillary 20 Another end opening leads to the bottom of the reaction tube main body.Pipe holder 17, including two seals circle 21 are reacted, sealing ring 21 will be anti- Should pipe 16 be fixed on it is described reaction pipe holder 17 on；Opening, the open at one end and the reaction are carried on the sealing ring 21 The open butt joint of capillary 20 in the side wall of pipe 16, the other end are plugged into catheter or airway tube.Reaction tube can also be flask etc. its His reaction vessel, capillary can be passed through during the course of the reaction or at the end of reaction and import liquid or gas；Led by capillary The bottom that the liquid or gas entered is passed directly into container body will not cause the splashing of original liquid in container body, export reaction Also without by other instruments during liquid in container.Meanwhile the reaction tube and reaction tube support Design cause reaction system Become more flexible, the pipetting of five bottles of reaction solutions, the heated at constant temperature of reaction system, cooling, mixing, azeotropic vaporization, acid and alkali hydrolysis, The flows such as drug delivery are able to integrated realization in this design；Decoction reactant is realized especially by the capillary of side wall System follows program to lift, during in different height the mixing of system be not required to by other extra pipelines and mix equipment can Achieve the goal.In addition, the hardware foundation that the malleation transmission for being designed as final product provides closed container is supporting.
Heating unit by airtight heating rustless steel container (reserved reaction tube lift physical space) that capacity is 300 milliliters, Evaporate the compositions such as silicone oil, electron temperature inductor and program control type temperature controller of the fusing point more than 250 DEG C.Perseverance is provided for synthesizer Warm heating condition so that the step such as azeotropic vaporization, synthetic reaction and sour water solution synthesizes according to user to be needed in a temperature hierarchy It is achieved with different temperatures system integration.The oil bath temperature of one side heating unit passes through temperature controller, cooling fan and journey Sequence control unit automatically controls；Programming rate is up to 20 DEG C/min, 10 DEG C/min of cooling rate.Can be flexible using the function Evaporation, reaction and the hydrolysis temperature of adjustment system, reach optimal combined coefficient.In addition, the system in the another aspect invention Software has reserved washability program module, can meet the research and development requirement of user, voluntarily write and call F-18 mark it is new just Electronics radiomimetic drug synthesis program, the synthesis system can be expanded more easily as synthesis18F-FLT、18F- acetyl courages Alkali,18The F-18 such as F-FMISO mark the multifunction module of new scientific research positron radiopharmaceuticals.
As shown in figure 1, malleation transmission unit 7 includes purified high pressure, high purity nitrogen 24, malleation transmission air valve 22, machinery The coordinated of formula pressure-reducing valve 23 and reaction member 5 and automation sample-adding unit 4.This unit normally synthesizes required nitrogen pressure Push and recommend 10Psi-20Psi, belong to low pressure, such low pressure (about 1 kilogram of atmospheric pressure) can ensure that mixing air valve V0 opens When, mixing severe degree is suitable, decoction will not be caused to splash, when the decoction of automatic sample unit 4 is passed into reaction tube 16, transmission Steadily, will not splash.But when transmitting medicine (reaction tube, which is gone up, to be come, the plug sealing reaction mouth of pipe), because reaction tube 16 is special Plug has 5 pipes extractions to come respective bottle, is sealed between bottleneck flexible glue lid and pipe and bad, therefore many gas leakage be present Point, 15Psi or so low-pressure nitrogen are not enough to come out finished medicines hydraulic pressure, and pass through resistance larger splitter and sterile film, Enter in decoction sub-bottling.To solve the problem, using 60-80Psi nitrogen, while V0 is opened, V2, V3, five gas of V4, V5 Valve, directly settled at one go with powerful air pressure and decoction is transmitted out, it is time saving and energy saving, reduce transfer trouble and reduce secondary dirt Dye.Thoroughly solve the technology barriers of synthesis module malleation transmission so that the design concept of transfer process more meets pharmaceutical production Management regulation, while the time for drug delivery of knowing clearly is greatly shortened, realize the full-automatic synthesis of real meaning.
At present, double-tube method fluorine-18 multifunctional module and small modules formula multifunction automatic F-18 mark PET pharmaceutical synthesis Instrument can not all solve the problems, such as that medicine malleation is transmitted, it is necessary to using one safety flack of a vacuum pump system and introducing, so grasp Work not only adds additional a link in drug delivery flow, extend the time of drug delivery；And the theory designs Good manufacturing practice (GMP) is not met, can be to production most when the inert gas for providing pressure does not pass through purified treatment End-product brings pollution into；Easily because vavuum pump negative pressure system breaks down radiopharmaceutical can be caused not pass in practice Defeated or safety flack and waste liquid bottle liquid mix and cause medicine to be contaminated.This equipment is by the design of malleation transmission unit 7, thoroughly Solve the technology barriers of synthesis module malleation transmission so that the design concept of transfer process more meets pharmaceutical production management rule Model, while the time for drug delivery of knowing clearly is greatly shortened, realize the full-automatic synthesis of real meaning.
As shown in figure 4, cold-hot wind cycling element 8 includes air heater 25 and exhaust fan 26.Water-acetonitrile in reaction member 5 Temperature in hot air circulation unit holding system must be utilized to be higher than 80 during the 3rd bottle of unnecessary acetonitrile of azeotropic vaporization and evaporation DEG C so that the gaseous material for turning into steam after being evaporated in reaction tube 16 is pulled away rapidly with the direction of circulating current；Otherwise can be because For reaction tube 16 it is meticulous, long cause gaseous material to condense again and can not effectively steam.Hot air circulation unit on the one hand can With the stability of guarantee system azeotropic water removing, the time required for being on the other hand substantially shorter evaporation process synthesizes so as to shorten The reaction time of system.After reaction tube each time removes from constant temperature oil bath, need to circulate using cold wind before decoction is added Part rapidly cools down reaction tube, occurs when avoiding adding decoction high-temperature denatured and reaction tube before decoction participation system reaction Burst.
As shown in Fig. 2 cold-hot wind cycling element 8 designs pairing into complete monitoring by transparent window 27.Building-up process bag Containing transfer factor, the moisture of acetonitrile and water azeotropic vaporization system, five bottles with the transmission of liquid, the reaction of system, intermediate product water All too many levels such as solution and the transmission of medicine malleation, failure and accident occurs unavoidably in centre, if can in real time monitor and adopt in time Take manual mode to exclude, can avoid the occurrence of unnecessary turkey completely and reach the purpose of superelevation synthesis success rate.Mesh It is preceding also to possess both at home and abroad without any a synthesis module to each step during synthesis and technological process of production realization Complete monitoring, so as to reach failure and the unexpected purpose excluded in time to occurring in synthesis.The alternative embodiments of the present invention In, it can be mounted with that a length is 20 centimetres in the front design in cold-hot wind cycling element 8, width is 10 centimetres transparent Safety glass observation window, it is real to each step during synthesis and the technological process of production using the outer observing window design of uniqueness Existing complete monitoring.
In the alternative embodiments of the present invention, two sets of synthesis modules are sour water solution synthesis model；Or it is that basic hydrolysis is closed Become the mode；Or while it is sour water solution synthesis model, another side is basic hydrolysis synthesis model.Acid, macromolecule alkali for hydrolysis pattern are at one Solved in synthesis module.By writing and calling the software module formula of different solidifications voluntarily to write the control software system of research and development System, can select sour hydrolysis pattern and basic hydrolysis pattern as desired.When selecting sour water solution pattern, synthetic reaction pipe passes through journey Sequence control, which adds the 0.50-1.50N of concentration hydrochloric acid and dropped in the oil bath of system E balance, to be implemented；When selection basic hydrolysis During pattern, synthetic reaction pipe adds the 0.20-0.50N of concentration NaOH by programme-control, and reaction solution does not enter the flat of system E In the oil bath of weighing apparatus, and in normal temperature and nitrogen mixing condition Rapid Implementation.Formula can be pre-installed according to the real needs of user in this Decoction, flexibly selected before synthesis.
Embodiment 2
A kind of double batch PET developers18F-FDG pharmaceutical synthesis methods, by improved catalysts ratio and formula, contract significantly The reaction time of short synthesis system.K2.2.2Solution/K2CO3The application target of catalyst is the radiation in order to be captured by QMA posts Property nucleic F-18 is eluted on request to be discharged into specified reaction system.K2.2.2Solution/K2CO3Catalyst is organic phase and inorganic phase Combined balance system system, organic phase and the ratio of inorganic phase are about 3 in tradition:1, in combined balance system system shared by inorganic phase water Ratio is higher, improves K2.2.2Solution/K2CO3The purpose of catalyst is before ensureing to elute release radionuclide F-18 effects Put, (this formula rate is 5 to the ratio shared by reduction combined balance system system reclaimed water:1) time of azeotropic water removing, is shortened so as to contract Short module entirety generated time.Improve K2.2.2Solution/K2CO3The formula of catalyst solution：60mg carbonic acid is accurately weighed with balance Potassium (K2CO3) 10ml drying beakers are placed in, (solution #1) is fully dissolved with 3.0ml high purity waters, 200mg ammonia is accurately weighed with balance Base polyethers K2.2.2It is placed in the sterile dry receiving flasks of 30ml, is dissolved with 17.0ml anhydrous acetonitriles and use the embedding good seal of gland (solution # 2).It is slowly added dropwise after solution #1 is drawn with 5ml syringes in the receiving flask for containing solution #2, is gently shaken in drop It is dynamic, it is sufficiently mixed organic phase and inorganic phase solution, the incorporation time about 5 minutes or so.1 point is gently shaken after mixing again Clock, stands whether observation mixed solution is clarified.It is labelled to be positioned over (term of validity about 30 days) standby in 4 DEG C of refrigerators.The improvement Formula considerably reduces the ratio in water in catalyst inorganic organic liquid mixture, reduces in acetonitrile and water azeotropic vaporization system Moisture evaporation time；Ensure to reach the purpose for shortening generated time on the basis of combined coefficient.Summarizing experiment experience, cold In experiment and simulation heat experiment, by groping, on the basis of combined coefficient is ensured, by generated time when taking sour hydrolysis pattern Shortening about 16 minutes than external synthesis module, (external general synthesis module generated time is averagely about 40 minutes, is shortened 40%). It is also very important breakthrough that this, which is broken through to the Short half-life nuclides that half-life period is 107 minutes,.
Concentration is used in alkaline hydrolysis process as 0.20-0.50N；Volume is 2.0ml NaOH solution；Mixed in normal temperature and nitrogen Rapid Implementation can be stablized and efficient synthetic yield under the conditions of conjunction.The hydrolyzation system hydrolysis time is only 90 seconds, stable For 100%；Synthetic yield is more than 65% (after radioactive decay correction).After improved formulations and basic hydrolysis scheme using the present invention, The synthesis total time of complete machine is only 12 minutes, at present had been reported that both at home and abroad in when being synthesized under the conditions of ensureing synthetic yield Between most short ripe synthesis module.
Concentration is used in acid hydrolysis as 0.5-1.5N；Volume is 2.0ml hydrochloric acid solution；It it is 116 DEG C in temperature Implement to be stablized and efficient synthetic yield in the system of silicone oil bath.Acid hydrolysis systems hydrolysis total time is only 9 minutes, Well below the Tracer lab FX FN of GE's (medical system) (GE companies) research and development18F- is multi-functional certainly It is dynamic to be combined to instrument (20 minutes), the CPCU synthesizers (18 minutes) of CTI companies of the U.S.；Stabilize to 100%；Synthetic yield is more than 80% (after radioactive decay correction).
The preparation of AG11A8-AG50 purification columns
About 2 grams of AG11A8 resins are initially charged with into the Bio-Rad splitters dried, gently knocking makes its even (account for whole piece Separate the half of column volume；About 1 gram of AG50 resin is reloaded into, gently knocking makes its is even (to account for whole piece separation column volume A quarter).Using preceding post is crossed with 10ml sterilized waters.
QMA post activation process：
1MNaHCO3 solution 10ml are taken with 10ml syringes, slowly elute QMA posts, speed can not be too fast, not allow liquid Bunchiness flows out.
Dry air is inhaled with 10ml syringes and blows QMA trapping columns three times, dries up residual liquid.(after performing step operation, should It can deposit one week and use after being sealed after post both sides are closed in 4 DEG C of refrigerators).
10ml high purity waters are being taken with 10ml syringes using preceding, are slowly eluting QMA trapping columns, speed can not be too fast, should not Liquid bunchiness is allowed to flow out.
Dry air is inhaled with 10ml syringes and blows QMA trapping columns three times, dries up residual liquid.
10ml HPLC acetonitriles are taken slowly to elute QMA trapping columns with 10ml syringes, speed can not be too fast, drop by Drop, liquid bunchiness is not allowed to flow out.
It is certain it is noted that resistance situation during propulsive liquid body when paying attention to eluting QMA trapping columns with above-mentioned three kinds of liquid, if gone out Existing resistance is excessive, particularly uses NaHCO3Solution elution resistance should stop using the QMA trapping columns when excessive.Simultaneously in propulsive liquid body During want situation around close observation pillar, in addition to liquid outlet around pillar should be unable to liquid body exudate, if there is Around pillar, along position liquid body exudate under being particularly, the QMA trapping columns should be stopped using；Otherwise turn in nucleic transmission and nucleic Can occur surprisingly, influenceing to synthesize success rate because resistance is excessive during shifting.
In acid-hydrolyzed method, the serum bottle numbering of V1, V2, V3, V4 and V5 control is respectively：#1, #2, #3, #4 and # 5.In sour water solution, the decoction in serum bottle is respectively：
#1：0.8ml K2.2.2Solution/K2CO3Solution (the K containing 10mg2.2.2With 3mg K2CO3), fully to be shaken before Mixing.
#2：1.2ml anhydrous acetonitrile
#3：(mannose triflate containing 15-20mg, pays attention to 1.0ml anhydrous acetonitriles：Must waterproof)
#4：The hydrochloric acid solution that 2.0ml concentration is 1.0M (pays attention to：It can not be pipetted and be emptied with syringe needle)
#5：10ml sterilizeds water for injection.
In the method for basic hydrolysis, the serum bottle numbering of V1, V2, V3, V4 and V5 control is respectively：#1, #2, #3, #4 and # 5.In basic hydrolysis, the decoction in serum bottle is respectively：
#1：0.8ml K2.2.2Solution/K2CO3Solution (the K containing 10mg2.2.2With 3mg K2CO3), fully to be shaken before Mixing.
#2：1.2ml anhydrous acetonitrile
#3：(mannose triflate containing 15-20mg, pays attention to 1.0ml anhydrous acetonitriles：Must waterproof)
#4：1.5ml concentration is 0.25N NaOH solutions
#5：10ml sterilizeds water for injection.
Preparatory items before synthesis include following item：
Front opening oil bath in 40 minutes switchs before synthesis, allows equalized temperature.
The reaction tube and pipe-line system more renewed.
Before five bottles of synthetic fluids, QMA trapping columns are connected on pharmaceutical synthesis module relevant position, while pull pressure pipe back and forth Silicone tube on valve, it is at nature closed mode.
First bottle of opening position is positioned over 2.0ml HPLC acetonitriles, is plugged liquid and tracheae, manual mode detection QMA pipelines Whether system and Valve for compressing tubular liner work are normal.Pay attention at least being dried up pipeline within 90 seconds with the time.
With mirror check module air pressure and flow whether in normal range (NR).
Synthesis assembling and formula：
Prepare 5 bottles of reaction liquids are put into relevant position, pass liquid Teflon pipes and flue by fool proof mark difference It is connected on each bottle, is installed on synthesis module.
Installation AG11A8-AG50 purification columns are simultaneously followed by Alumina-N plus C18 combined columns in the post.Sterile mistake is connect again Filter and product receiving flask.It is positioned in activity meter.
Activation system software, the left side or the right synthesis program are selected, selection sour water solution or basic hydrolysis mould are required according to user Formula, synthesis module is initialized,
Accelerator production nucleic is finished, and nucleic is all defeated to after QMA, and transmission F- is clicked in software initialization program F-18 nucleic on QMA posts is eluted in reaction tube by 18 nucleic keys, first bottle of catalyst liquid.
By software auto-control flow, after being automatically synthesized, read activity and count.
Product receiving flask is taken out, measures radioactive concentration and radiochemical purity.
(bottle, adsorption column and resin are disposable use to all bottles of (minimum to be spaced 24 hours) taking-up before next use Product), reaction tube and plug.Reaction tube and plug are cleaned, so that next time is just used.
The present invention carries out production checking to each technological process of production of synthesis module；It is cured to using synthetic parameters after checking Operate in software, synthesis module has carried out 100 batches18F-FDG medicine production (acid, each 50 batch of basic hydrolysis pattern), and With reference to《Chinese Pharmacopoeia 2015 editions》It is right18F-FDG quality control requirement carries out quality control to the quality of every batch medicine.Simultaneously Nat'l Pharmaceutical ＆ Biological Products Control Institute is to being produced by the set synthesis module18F-FDG carry out the detection of 3 batch medicine qualifications；Take Obtain qualified examining report book.
Above content is to combine specific preferred embodiment further description made for the present invention, it is impossible to is assert The specific implementation of the present invention is confined to these explanations.For those skilled in the art, do not taking off On the premise of from present inventive concept, some equivalent substitutes or obvious modification can also be made, and performance or purposes are identical, all should When being considered as belonging to protection scope of the present invention.

Claims (10)

  1. A kind of 1. double batch PET developers18F-FDG pharmaceutical synthesis equipment, it is characterised in that including：The shunting choosing of F-18 nucleic Select module and double batch synthesis modules；
    Double batch synthesis modules include two sets of synthesis modules of binary channel design；
    The synthesis module includes：F-18 anion processing units,18The recyclable unit of O- heavy-oxygen-enriched waters, automatic sample unit, reaction Unit, heating unit, malleation transmission unit and cold-hot wind cycling element；
    F-18 anion processing unit of the shunting selecting module of the F-18 nucleic respectively with two sets of synthesis modules is connected；It is described F-18 anions processing unit respectively with it is described18The recyclable unit of O- heavy-oxygen-enriched waters is connected with automatic sample unit；It is described to add automatically Sample unit is joined directly together with the reaction member or is connected by F-18 anions processing unit with the reaction member, described anti- Answer unit to be connected respectively with the heating unit and the malleation transmission unit, the cold-hot wind cycling element reaction member, Heating unit covers on together.
  2. 2. double batch PET developers as claimed in claim 118F-FDG pharmaceutical synthesis equipment, it is characterised in that described two sets Synthesis module is sour water solution synthesis model；Or it is basic hydrolysis synthesis model；Or while be sour water solution synthesis model, another side For basic hydrolysis synthesis model.
  3. 3. double batch PET developers as claimed in claim 118F-FDG pharmaceutical synthesis equipment, it is characterised in that the F-18 The electronic three-way valve of changeable path is set to realize between the shunting selecting module of nucleic and the F-18 anions processing unit Nucleic shunts.
  4. 4. double batch PET developers as claimed in claim 118F-FDG pharmaceutical synthesis equipment, it is characterised in that the malleation Transmission unit includes malleation transmission air valve and mechanical pressure-reducing valve, transmits out by decoction using 60-80Psi nitrogen.
  5. 5. double batch PET developers as claimed in claim 118F-FDG pharmaceutical synthesis equipment, it is characterised in that the F-18 The QMA trapping columns capture F-18 anions of anion processing unit, the catalyst solution of the automatic sample unit are caught via QMA Obtain post elution release F-18 anions and be sent to the reaction member.
  6. 6. double batch PET developers as claimed in claim 118F-FDG pharmaceutical synthesis equipment, it is characterised in that the reaction Unit includes reaction vessel and reaction vessel support；
    The reaction vessel includes container body and capillary, and the one end open of the capillary is arranged on the container body In the side wall of openend, closed or drained by the sealing ring with opening；Another end opening of the capillary leads to institute State the bottom of container body；
    Reaction vessel is fixed on the reaction vessel support by reaction vessel support, including two seals circle, sealing ring；It is described Opening is carried on sealing ring, the open at one end is docked with the capillary apertures in the reaction vessel side wall, and the other end is plugged into Catheter or airway tube.
  7. 7. double batch PET developers as claimed in claim 118F-FDG pharmaceutical synthesis equipment, it is characterised in that18O- heavy-oxygen-enriched waters Recyclable unit will by triple valve18The collecting of O- heavy-oxygen-enriched waters and light water separates.
  8. 8. double batch PET developers as claimed in claim 118F-FDG pharmaceutical synthesis equipment, it is characterised in that described cold and hot Transparent window is set on wind cycling element.
  9. A kind of 9. double batch PET developers18F-FDG pharmaceutical synthesis methods, it is characterised in that K2.2.2Solution/K2CO3Catalyst is molten The preparation method of liquid includes：
    S1：Prepare K2CO3Solution：60mg K2CO3It is dissolved in 3.0ml high purity waters；
    S2：Prepare K2.2.2Solution：200mg K2.2.2It is dissolved in 17.0ml anhydrous acetonitriles；
    S3：By the K of preparation2CO3Solution and K2.2.2Solution is sufficiently mixed, and refrigeration is stand-by.
  10. 10. double batch PET developers as claimed in claim 918F-FDG pharmaceutical synthesis methods, it is characterised in that reaction member Add the 0.50-1.50N of concentration hydrochloric acid；When selecting basic hydrolysis pattern, reaction member adds the 0.20-0.50N's of concentration NaOH solution.
CN201710687609.4A 2017-08-11 2017-08-11 Double-batch PET developer18F-FDG drug synthesis equipment and method Active CN107474082B (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111261307A (en) * 2020-01-22 2020-06-09 赛诺联合医疗科技（北京）有限公司 Preparation device of radioactive source die body
CN113955771A (en) * 2021-10-29 2022-01-21 北京善为正子医药技术有限公司 Automatic synthesis method for rapidly preparing 18F sodium fluoride PET (polyethylene terephthalate) medicine
CN114713157A (en) * 2022-06-09 2022-07-08 北京先通国际医药科技股份有限公司 Apparatus for producing liquid composition, method for producing the same and use thereof

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0798307A1 (en) * 1996-03-29 1997-10-01 NKK Plant Engineering Corporation Fluoro-deoxyglucose synthesizer using columns
CN1398870A (en) * 2001-07-26 2003-02-26 张锦明 Prepn apparatus and process for 2-fluoro-18 substituent-2 deoxy-beta-D-glucose
US20040022696A1 (en) * 2000-05-12 2004-02-05 Cti, Inc. Method for multi-batch production of FDG
CN1765911A (en) * 2005-11-18 2006-05-03 南方医科大学南方医院 2- 18The synthesis technique of F-2-DDG
CN1966140A (en) * 2006-03-22 2007-05-23 上海化工研究院 Chemical synthesizer capable of preparing multiple fluoro-marking agent
CN1974587A (en) * 2006-11-30 2007-06-06 中国人民解放军第三军医大学野战外科研究所 Basic hydrolysis process for preparing 2-fluoro [18F]-2-deoxy-beta-D-glucose in single tube FDG acidic hydrolysis apparatus
CN103772447A (en) * 2012-10-18 2014-05-07 上海原子科兴药业有限公司 Improved FDG synthesis method
CN104262073A (en) * 2014-09-30 2015-01-07 北京善为正子医药技术有限公司 Small modular multifunctional automatic 18F labelling PET (positron emission tomography) drug synthesizer

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0798307A1 (en) * 1996-03-29 1997-10-01 NKK Plant Engineering Corporation Fluoro-deoxyglucose synthesizer using columns
US20040022696A1 (en) * 2000-05-12 2004-02-05 Cti, Inc. Method for multi-batch production of FDG
CN1398870A (en) * 2001-07-26 2003-02-26 张锦明 Prepn apparatus and process for 2-fluoro-18 substituent-2 deoxy-beta-D-glucose
CN1765911A (en) * 2005-11-18 2006-05-03 南方医科大学南方医院 2- 18The synthesis technique of F-2-DDG
CN1966140A (en) * 2006-03-22 2007-05-23 上海化工研究院 Chemical synthesizer capable of preparing multiple fluoro-marking agent
CN1974587A (en) * 2006-11-30 2007-06-06 中国人民解放军第三军医大学野战外科研究所 Basic hydrolysis process for preparing 2-fluoro [18F]-2-deoxy-beta-D-glucose in single tube FDG acidic hydrolysis apparatus
CN103772447A (en) * 2012-10-18 2014-05-07 上海原子科兴药业有限公司 Improved FDG synthesis method
CN104262073A (en) * 2014-09-30 2015-01-07 北京善为正子医药技术有限公司 Small modular multifunctional automatic 18F labelling PET (positron emission tomography) drug synthesizer

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111261307A (en) * 2020-01-22 2020-06-09 赛诺联合医疗科技（北京）有限公司 Preparation device of radioactive source die body
CN111261307B (en) * 2020-01-22 2022-03-08 赛诺联合医疗科技（北京）有限公司 Preparation device of radioactive source die body
CN113955771A (en) * 2021-10-29 2022-01-21 北京善为正子医药技术有限公司 Automatic synthesis method for rapidly preparing 18F sodium fluoride PET (polyethylene terephthalate) medicine
CN114713157A (en) * 2022-06-09 2022-07-08 北京先通国际医药科技股份有限公司 Apparatus for producing liquid composition, method for producing the same and use thereof

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