CN114653250A - Method for preparing raw materials for medicinal nucleic acid synthesis - Google Patents

Method for preparing raw materials for medicinal nucleic acid synthesis Download PDF

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Publication number
CN114653250A
CN114653250A CN202210307136.1A CN202210307136A CN114653250A CN 114653250 A CN114653250 A CN 114653250A CN 202210307136 A CN202210307136 A CN 202210307136A CN 114653250 A CN114653250 A CN 114653250A
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preparing
nucleic acid
raw materials
preparation
synthesis
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刘宗文
门静涛
刘倩
朱桃花
周淮玉
周金山
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General Biology Chuzhou Co ltd
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General Biology Chuzhou Co ltd
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Abstract

The invention discloses a raw material pre-preparation method for medicinal nucleic acid synthesis, which specifically comprises the following steps: the method comprises the following steps: preparing a column before synthesis: manually filling the solid carrier into a synthesis column, connecting the synthesis column with a synthesizer, introducing acetonitrile into the synthesizer through a closed pipeline to enable the solid carrier to be uniformly filled, and after the solid carrier is uniformly filled, conveying the waste acetonitrile into a waste liquid tank through a pipeline; step two: preparing raw materials before preparing nucleic acid synthesis, and preparing the nucleic acid raw materials by adopting a raw material pre-preparation device, wherein the raw materials mainly comprise deprotection solution preparation, activator preparation, vulcanizing agent preparation, oxidant preparation, cap solution preparation, base monomer liquid preparation and amine washing solution preparation; according to the invention, the plurality of groups of the material mixing tanks arranged on the material mixing base are respectively used for mixing different raw materials for nucleic acid synthesis, and the same group of pre-mixing devices is adopted for mixing different raw materials simultaneously, so that the raw material mixing efficiency is effectively improved.

Description

Method for preparing raw materials for medicinal nucleic acid synthesis
Technical Field
The invention relates to the technical field of medicinal nucleic acid synthesis devices, in particular to a method for pre-preparing raw materials for medicinal nucleic acid synthesis.
Background
The medicinal nucleic acid is widely applied to the development of small nucleic acid drugs and the development of novel vaccine adjuvants. The development of a drug can be roughly divided into three stages, namely: small molecule drugs, protein antibody drugs, nucleic acid drugs. In recent years, the third generation of drugs based on nucleic acid therapy has been developed rapidly, and nucleic acid drugs are characterized in that they can be directly combined with pathogenic genes and prevented from translating, thereby preventing the production of pathogenic proteins, and small molecular drugs and protein antibody drugs, nucleic acid drugs can be guided accurately and reach targets, and are easy for industrial amplification production.
Medicinal nucleic acid needs to use the dosing unit to carry out the pre-allocation to the raw materials in advance in synthetic production process, and present dosing unit adopts split type structure, and different raw materials dispose on different equipment, and the management of being not convenient for leads to inefficiency.
Disclosure of Invention
The invention aims to provide a raw material pre-preparation method for medicinal nucleic acid synthesis, which is characterized in that a plurality of groups of material tanks are arranged on a material preparation base and are respectively used for preparing different raw materials for nucleic acid synthesis, the different raw materials are simultaneously prepared by adopting the same group of pre-preparation devices, the preparation efficiency of the raw materials is effectively improved, a feeding component is arranged for feeding the raw materials into the material tanks, and a tank cover component can be used for sealing or uncovering the material tanks according to needs, so that the automatic control is convenient and quick.
The purpose of the invention can be realized by the following technical scheme:
a method for preparing raw materials for synthesizing medicinal nucleic acid comprises the following steps:
the method comprises the following steps: preparation before Synthesis
Column assembling: manually filling the solid carrier into a synthesis column, connecting the synthesis column with a synthesizer, introducing acetonitrile into the synthesizer through a closed pipeline to enable the solid carrier to be uniformly filled, and after the solid carrier is uniformly filled, conveying the waste acetonitrile into a waste liquid tank through a pipeline;
step two: raw material preparation
The method comprises the steps that raw materials are required to be configured before nucleic acid synthesis, a raw material pre-configuration device is adopted to configure the nucleic acid raw materials, and the method mainly comprises deprotection solution configuration, activating agent configuration, vulcanizing agent configuration, oxidizing agent configuration, cap solution configuration, base monomer liquid configuration and amine washing solution configuration;
step three: through a plurality of groups of material tanks arranged on the material mixing base, different raw materials for nucleic acid synthesis are respectively configured, the different raw materials are simultaneously mixed by adopting the same group of pre-configuration devices, the material charging component is arranged to charge materials into the material mixing tank, and the material mixing tank can be sealed or uncapped by the tank cover component as required;
step four: the third motor drives the drive shaft and rotates, and the drive shaft drives the connecting seat through the drive plate and rotates, drives the (mixing) shaft through the connecting seat and rotates, stirs the mixture through a plurality of stirring rod sets to jar internal portion raw materials, realizes the pre-prepared to the raw materials.
As a further scheme of the invention: the temperature of the toluene and the dichloroacetic acid mixed process in the deprotection agent preparation process is 60 ℃, and the other raw material preparation processes are carried out at normal temperature.
As a further scheme of the invention: the preparation process of the deprotection agent adopts glycol as a cold and hot medium, and the glycol adopts steam for indirect heating and adopts chilled water for cooling.
As a further scheme of the invention: organic waste gas generated in the configuration process is collected through an air suction hood or a ventilation cabinet, and the waste gas is guided to a waste gas treatment facility for treatment after being collected.
As a further scheme of the invention: the raw material pre-preparation device comprises a main body frame, a first motor is fixedly arranged at the central position of the bottom of the main body frame, a material preparation base is arranged at the central position of the upper end of the main body frame, and the material preparation base is fixedly connected with an output shaft of the first motor; the upper end of the batching base is provided with a plurality of groups of material tank grooves, and the material tank grooves are used for installing batching tanks;
the upper end of the main body frame is fixedly provided with a connecting bracket, and a feeding component for adding raw materials into the batching tank is arranged on the connecting bracket;
main part frame upper end central point puts and is provided with the cover subassembly, and the cover subassembly is used for carrying out the closing cap to the batching jar.
As a further scheme of the invention: the batching base bottom is provided with the motor groove, and the motor groove is corresponding with material jar trench position and quantity, and the motor inslot is installed the stirring subassembly.
As a further scheme of the invention: the batching jar is including jar body and the base of setting in jar body bottom, and the base lower extreme is provided with a plurality of locating holes, is provided with the reference column with locating hole matched with on the feed tank groove.
As a further scheme of the invention: the stirring assembly comprises a connecting seat rotatably installed at the bottom of the base, a stirring shaft is fixedly connected to the connecting seat, and a plurality of groups of stirring rods are uniformly installed on the shaft rod extending into the tank body.
As a further scheme of the invention: the stirring assembly further comprises a third motor fixedly installed in the motor groove, the output end of the third motor is fixedly connected with a driving shaft, the driving shaft penetrates through a batching base fixedly connected with a driving plate, and a driving hole matched with the driving plate is formed in the connecting seat.
As a further scheme of the invention: the feeding assembly comprises a cylindrical pipe fixedly arranged on the connecting support, and a prism pipe is arranged at the lower end of the cylindrical pipe.
As a further scheme of the invention: the periphery of the prism pipe is sleeved with a connecting sleeve, the periphery of the connecting sleeve is fixedly connected with a connecting support plate, the lower end of the connecting support is fixedly provided with a second driving cylinder, and the output end of the second driving cylinder is fixedly connected with the connecting support plate.
As a further scheme of the invention: the cover subassembly is including the fixed spacing seat that sets up in batching base upper end central point and put, and spacing seat periphery is rotated and is installed and rotate the cover, rotates the cover periphery and is provided with the multiunit connecting plate, fixedly connected with apron on the connecting plate.
As a further scheme of the invention: the periphery of the rotating sleeve is provided with a sliding groove, the connecting plate is slidably mounted on the sliding groove, the lower portion of the rotating sleeve is fixedly provided with a bottom plate, a first driving cylinder is fixedly mounted on the bottom plate, and the output end of the first driving cylinder is fixedly connected with the connecting plate.
As a further scheme of the invention: an annular rack is arranged on the inner side wall of the rotating sleeve, a second motor is fixedly mounted on the batching base, and a driving gear matched with the annular rack is fixedly mounted on an output shaft of the second motor.
The invention has the beneficial effects that:
(1) through a plurality of groups of material tanks that set up on the batching base, be used for disposing the synthetic different raw materials of nucleic acid respectively, different raw materials adopt and carry out the batching simultaneously with a set of pre-prepared device, effectively improve the configuration efficiency to the raw materials to set up reinforced subassembly and reinforced in to the batching jar, and the cover subassembly can carry out the closing cap or uncap, automated control convenient and fast to the batching jar as required.
(2) Move down through adapter sleeve and stretch into jar internal portion for add the raw materials to jar internal, this kind of mode adds the raw materials and can effectively prevent that the raw materials from taking place to sputter or scattering, reduces the waste of raw materials on the one hand, and on the other hand prevents the polluted environment.
(3) Drive gear through the second motor and rotate, drive gear drive annular rack and rotate the cover and rotate, thereby drive connecting plate and apron and rotate, rotate directly over the jar body when needs are to jar body closing cap, when need not carrying out the closing cap, rotate the apron to one side of the jar body, and some for sealed lid of a plurality of laps, some for non-sealed lid, can rotate different apron and jar body according to the different processing demands of the jar body and cooperate, drive cylinder one and drive connecting plate and apron lifting movement, thereby drive the apron and carry out quick closing cap or open to the jar body.
Drawings
The invention will be further described with reference to the accompanying drawings.
FIG. 1 is a schematic structural view of the present invention as a whole;
FIG. 2 is a schematic view of the base of the present invention in partial cross-section;
FIG. 3 is a schematic cross-sectional view of the dispensing canister of the present invention;
FIG. 4 is a schematic top view of the can lid assembly of the present invention;
FIG. 5 is a schematic front view of the can lid assembly of the present invention;
FIG. 6 is a schematic cross-sectional view of the rotating sleeve of the present invention;
FIG. 7 is a schematic structural view of the charging assembly of the present invention;
FIG. 8 is a schematic structural view of a prismatic tube of the present invention;
fig. 9 is a schematic view of the construction of the connection sleeve of the present invention.
In the figure: 1. a main body frame; 2. a first motor; 3. a dosing base; 31. a motor slot; 32. a charging bucket groove; 33. a positioning column; 4. connecting a bracket; 5. a dosing tank; 51. a tank body; 52. a base; 53. positioning holes; 6. a can lid assembly; 61. rotating the sleeve; 62. a limiting seat; 63. a second motor; 64. a drive gear; 65. an annular rack; 66. a connecting plate; 67. a cover plate; 68. a base plate; 69. a first driving cylinder; 7. a feeding assembly; 71. a cylindrical tube; 72. a prismatic tube; 73. connecting a sleeve; 74. connecting the support plate; 75. a second driving cylinder; 8. a stirring assembly; 81. a third motor; 82. a drive shaft; 83. a drive plate; 84. a connecting seat; 85. a stirring shaft; 86. a stirring rod.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The synthesis process of the medicinal nucleic acid comprises the following specific steps:
1) preparation before Synthesis
Column assembling: the method comprises the steps of manually filling a solid carrier (polyethylene cross-linked divinylbenzene) into a synthesis column, connecting the synthesis column with a synthesizer, introducing acetonitrile into the synthesizer through a closed pipeline to enable the solid phase carrier to be uniformly filled, and after the solid phase carrier is uniformly filled, conveying waste acetonitrile into a waste liquid tank through a pipeline, wherein the waste acetonitrile is generated in the process.
2) Raw material preparation
The preparation method comprises the steps of preparing raw materials before nucleic acid synthesis, and preparing the nucleic acid raw materials by adopting a raw material pre-preparation device, wherein the preparation method mainly comprises the steps of preparing a deprotection solution, preparing an activating agent, preparing a vulcanizing agent, preparing an oxidizing agent, preparing a cap solution, preparing a base monomer in a liquid state and preparing an amine washing solution.
Referring to fig. 1, the invention is a method for pre-preparing raw materials for synthesizing medicinal nucleic acid, comprising a main body frame 1, a first motor 2 is fixedly arranged at the central position of the bottom of the main body frame 1, a batching base 3 is arranged at the central position of the upper end of the main body frame 1, and the batching base 3 is fixedly connected with an output shaft of the first motor 2; a plurality of groups of material tank grooves 32 are formed in the upper end of the batching base 3, and the material tank grooves 32 are used for installing batching tanks 5; the upper end of the main body frame 1 is fixedly provided with a connecting bracket 4, and a feeding component 7 for adding raw materials into the batching tank 5 is arranged on the connecting bracket 4; the upper end central point of main part frame 1 puts and is provided with cover subassembly 6, and cover subassembly 6 is used for carrying out the closing cap to batching jar 5.
Through a plurality of groups of batching jar 5 that set up on the batching base 3, be used for disposing the synthetic different raw materials of nucleic acid respectively, different raw materials adopt and carry out the batching simultaneously with a set of pre-prepared device, effectively improve the configuration efficiency to the raw materials to set up reinforced subassembly 7 and reinforced in batching jar 5, and cover subassembly 6 can carry out the closing cap or uncap, automated control convenient and fast to batching jar 5 as required.
Referring to fig. 2 and 3, a motor groove 31 is formed in the bottom of the batching base 3, the motor groove 31 corresponds to the material tank grooves 32 in position and quantity, and the stirring assembly 8 is installed in the motor groove 31. The batching tank 5 comprises a tank body 51 and a base 52 arranged at the bottom of the tank body 51, wherein a plurality of positioning holes 53 are formed in the lower end of the base 52, and positioning columns 33 matched with the positioning holes 53 are arranged on the charging tank groove 32.
Ensure jar body 51 stable installation on batching base 3 through setting up the feed tank groove 32 to utilize reference column 33 and locating hole 53 to cooperate and improve jar body 51's stability, when making stirring subassembly 8 stir jar internal portion, jar body 51 can not take place to rock and lead to droing.
Stirring subassembly 8 is including rotating connecting seat 84 of installing in base 52 bottom, fixedly connected with (mixing) shaft 85 on connecting seat 84, and the (mixing) shaft 85 stretches into evenly to install multiunit puddler 86 on the axostylus axostyle of jar body 51 inside. The stirring assembly 8 further comprises a third motor 81 fixedly installed in the motor groove 31, an output end of the third motor 81 is fixedly connected with a driving shaft 82, the driving shaft 82 penetrates through a driving plate 83 fixedly connected with the batching base 3, and a driving hole matched with the driving plate 83 is formed in the connecting seat 84.
Drive shaft 82 through third motor 81 and rotate, drive shaft 82 drives connecting seat 84 through drive plate 83 and rotates, drives (mixing) shaft 85 through connecting seat 84 and rotates, stirs the mixture through a plurality of puddler 86 to jar internal raw materials of body 51, realizes the pre-prepared to the raw materials.
Referring to fig. 7-9, the feeding assembly 7 includes a cylindrical tube 71 fixedly disposed on the connecting bracket 4, and a prism tube 72 is disposed at a lower end of the cylindrical tube 71. The periphery of the prism tube 72 is sleeved with a connecting sleeve 73, the periphery of the connecting sleeve 73 is fixedly connected with a connecting support plate 74, the lower end of the connecting support 4 is fixedly provided with a second driving cylinder 75, and the output end of the second driving cylinder 75 is fixedly connected with the connecting support plate 74.
The second driving cylinder 75 drives the connecting support plate 74 to move up and down, so that the connecting sleeve 73 is driven to move up and down, and moves downwards through the connecting sleeve 73 to stretch into the tank body 51 for adding raw materials into the tank body 51.
Referring to fig. 4-6, the tank cover assembly 6 includes a limiting seat 62 fixedly disposed at the center of the upper end of the ingredient base 3, a rotating sleeve 61 rotatably mounted on the periphery of the limiting seat 62, a plurality of sets of connecting plates 66 disposed on the periphery of the rotating sleeve 61, and a cover plate 67 fixedly connected to the connecting plates 66. The periphery of the rotating sleeve 61 is provided with a sliding groove, the connecting plate 66 is slidably mounted on the sliding groove, the lower portion of the rotating sleeve 61 is fixedly provided with a bottom plate 68, a first driving cylinder 69 is fixedly mounted on the bottom plate 68, and the output end of the first driving cylinder 69 is fixedly connected with the connecting plate 66. An annular rack 65 is arranged on the inner side wall of the rotating sleeve 61, a second motor 63 is fixedly mounted on the batching base 3, and a driving gear 64 matched with the annular rack 65 is fixedly mounted on an output shaft of the second motor 63.
Drive gear 64 through second motor 63 and rotate, drive gear 64 drives annular rack 65 and rotates with rotating sleeve 61, thereby drive connecting plate 66 and apron 67 and rotate, rotate directly over jar body 51 when needs cover jar body 51, when need not carry out the closing cap, rotate apron 67 to one side of jar body 51, and some for sealed lid of a plurality of apron 67, some are non-sealed lid, can rotate different apron 67 and jar body 51 and cooperate according to jar body 51's different processing demands, drive cylinder 69 drives connecting plate 66 and apron 67 elevating movement, thereby drive apron 67 and carry out the closing cap or open jar body 51.
The raw materials acetonitrile and toluene are respectively conveyed to a workshop acetonitrile tank and a toluene tank by a tank field conveying pump for storage and standby.
The barreled and bottled raw materials are manually transported to a workshop by a forklift.
In the preparation process of the deprotection agent, the temperature of the toluene and dichloroacetic acid mixing process is 60 ℃, ethylene glycol is used as a cold and hot medium, the ethylene glycol is indirectly heated by steam and cooled by chilled water, after uniform mixing, the deprotection solution is conveyed to a deprotection solution buffer tank by a pipeline for temporary storage, and the preparation processes of other raw materials are all carried out at normal temperature; in the raw material preparation process, toluene, acetonitrile and pure water are all conveyed to each preparation tank from a tank area by adopting a closed pipeline, PADS, iodine and base monomers are all solid materials, the materials are directly fed at a feeding port of each preparation tank, and a certain amount of dust is generated in the feeding process; the other raw materials of dichloroacetic acid, 3-methylpyridine, pyridine, acetic anhydride and diethylamine are barreled/bottled, the nitrogen is adopted to pressure feed the barreled materials to a basic monomer tank, an activator tank, a vulcanizing agent tank, an oxidant tank and the like, a small amount of organic waste gas is volatilized in the feeding process, all the preparation kettles need to be stirred in the raw material preparation process, and a certain amount of waste packaging barrels/bags are generated in the raw material preparation process.
Organic waste gas generated in the configuration process is collected through an air suction hood or a ventilation cabinet, and the waste gas is guided to a waste gas treatment facility for treatment after being collected.
3) Synthesis of
The synthesis process uses a full-automatic synthesizer to carry out full-automatic synthesis operation under the environment of normal temperature and full sealing, and the whole synthesis period is 24 hours. All the prepared raw materials are conveyed into a synthesizer through a pipeline, and the synthesizer is provided with synthesis columns of 350mm, 600mm and 800 mm. The chain extension reaction process is extension from 3 '-5' direction, mainly comprises 4 steps of deprotection, activation coupling, vulcanization/oxidation and capping, after the 4 steps of reaction are completed, the next round of chain extension reaction is carried out, and the number of chain extension reactions is about different according to different requirements, and is 30 on average.
4) Amine wash
After the four-step reaction is completed, the product and the solid-phase carrier in the synthesizer are subjected to amine washing, the product is washed by diethylamine, so that the diethylamine reacts with the protective group cyanoethyl to achieve the purpose of removing the protective group cyanoethyl, the washing time of the mixed solution of diethylamine and acetonitrile in the amine washing process is about 10min, and the waste liquid generated by washing is connected to a waste liquid storage tank through a pipeline.
Adopt acetonitrile to wash the synthesizer after the amine is washed and accomplish, get rid of the impurity in the synthesizer, synthetic post in the synthesizer washs to get rid of the residue in the synthetic post, carry to the waste liquid storage tank through airtight pipeline and keep in.
5) Cutting ammonolysis
After synthesis is finished, the synthetic column is transferred to an ammonolysis workshop, products after reaction in the synthetic column and solid phase carriers are transferred to an ammonolysis tank together, 25% ammonia water is pressurized to the ammonolysis tank from a storage barrel by adopting nitrogen, the operation temperature is 65 ℃, ethylene glycol is used as a cold and hot medium, the ethylene glycol is indirectly heated by adopting steam, cooling is carried out by adopting chilled water, oligo-nucleic acid synthesized on a solid phase support is eluted, the ammonia water containing the oligo-nucleic acid products is pressed into a movable tank through a nitrogen closed pipeline, a filter screen is additionally arranged in the pipeline, the solid phase carriers are filtered, a small amount of waste gas is generated in the process of feeding the ammonia water and opening the cover of the ammonolysis kettle, and a small amount of organic waste gas is volatilized in the process of opening the cover of the synthetic column.
6) And (3) purification:
the purification process adopts ion exchange in three production lines and reverse phase chromatography in one production line.
A. An ion exchange process:
a. early preparation:
(1) preparing 1m NaOH solution, 2m NaCl solution and disodium hydrogen phosphate solution in a preparation room;
(2) storing the prepared solution into a preparation tank of 3 kinds of buffer solution and transferring the solution to a column chromatography room;
b. and (3) a purification stage:
(1) the reaction product moving storage tank is connected to the interface of the purifier through a hose;
(2) conveying the NaOH solution, the NaCl solution and the phosphate solution to a bubble remover by adopting nitrogen pressure, entering an interface of a purifier through the bubble remover, firstly introducing the NaOH solution as a buffer solution to wash and balance the purification column, and taking the NaCl solution and the phosphate solution as eluents;
(3) pumping the reaction product into a purifier for ion exchange, separating the reaction product from impurities by using a buffer solution and an eluent, collecting a finished product after the separation is finished, and subpackaging the finished product into a collection bag;
(4) and waste liquid generated in the process is conveyed into a waste liquid tank through a closed pipeline.
The pollutants produced by this process are mainly wastewater.
B. And (3) reverse-phase chromatography process:
the purification process requires the addition of acetonitrile for reverse phase chromatography.
a. Early preparation
(1) Preparing 1m NaOH solution and TEAA (mixed solution of triethylamine and acetic acid) solution during preparation;
(2) the prepared solution is transferred to a temporary storage mobile transfer tank and is transferred to a purification workshop.
b. And (3) a purification stage:
(1) the reaction product moving storage tank is connected to the interface of the purifier through a hose;
(2) conveying NaOH solution and TEAA (mixed solution of triethylamine and acetic acid) solution into a bubble remover under the action of nitrogen pressure, and entering a purifier interface through the bubble remover;
(3) the acetonitrile is connected to a purifier interface by adopting a closed pipeline;
(4) and (4) after the column chromatography is carried out, subpackaging the finished product into a collection bag.
(5) And conveying the waste liquid generated in the chromatography process to a waste liquid tank through a closed pipeline. Waste gas generated in the purification process is absorbed by the universal air suction hood and then is sent to a waste gas treatment device.
7) And (3) ultrafiltration:
after the product is purified, salt substances brought in the purification are removed, and the product is desalted by an ultrafiltration method. Manually conveying the purified product to an ultrafiltration process by a cart, and rinsing the ultrafiltration membrane by 16% NaOH solution before ultrafiltration; after rinsing, replacement desalination is carried out by adopting injection water, the ultrafiltration membrane is replaced periodically in the ultrafiltration process, and the rinsing wastewater, the ultrafiltration wastewater and the waste ultrafiltration membrane are generated in the working procedure.
8) Subpackaging:
and after the ultrafiltration is finished, taking out the product from the subpackage bag, and manually subpackaging the product into small packaging bottles.
9) Freeze-drying: lyophilization is a drying process in which an aqueous material is frozen below freezing point (-40 ℃, 12h) to convert water to ice, and then the ice is removed by converting it to a vapor under a higher vacuum. The water vapor generated by freeze drying is collected by a low-temperature condenser to become ice, and then frost is changed into water, and freeze-drying wastewater is generated in the process.
10) Warehousing products: after the freeze drying is finished, the product is put in a warehouse for refrigeration, and the refrigeration temperature is-4 ℃.
While one embodiment of the present invention has been described in detail, the description is only a preferred embodiment of the present invention and should not be taken as limiting the scope of the invention. All equivalent changes and modifications made within the scope of the present invention shall fall within the scope of the present invention.

Claims (10)

1. A method for preparing raw materials for synthesizing medicinal nucleic acid is characterized by comprising the steps of preparing nucleic acid raw materials by adopting a raw material pre-preparing device, and simultaneously preparing different raw materials by adopting the same group of pre-preparing devices.
2. The method of claim 1, wherein the temperature of the mixture of toluene and dichloroacetic acid is 60 ℃ during the preparation of the deprotection agent, and the preparation of the other raw materials is performed at room temperature.
3. The method for preparing raw materials for medicinal nucleic acid synthesis according to claim 2, wherein glycol is used as a cold and hot medium in the deprotection agent preparation process, and the glycol is indirectly heated by steam and cooled by chilled water.
4. The method of claim 1, wherein the organic waste gas generated during the preparation process is collected by an air suction hood or a ventilation hood, and the waste gas is collected and then introduced to a waste gas treatment facility for treatment.
5. The method for pre-preparing the raw material for the synthesis of the medicinal nucleic acid according to claim 1, wherein the raw material pre-preparing device comprises a main body frame (1), a first motor (2) is fixedly arranged at the central position of the bottom of the main body frame (1), a material preparing base (3) is arranged at the central position of the upper end of the main body frame (1), and the material preparing base (3) is fixedly connected with an output shaft of the first motor (2); a plurality of material tank grooves (32) are formed in the upper end of the batching base (3), and the material tank grooves (32) are used for mounting batching tanks (5);
a connecting support (4) is fixedly arranged at the upper end of the main body frame (1), and a feeding assembly (7) for adding raw materials into the batching tank (5) is arranged on the connecting support (4);
main part frame (1) upper end central point puts and is provided with cover subassembly (6), and cover subassembly (6) are used for carrying out the closing cap to batching jar (5).
6. The method for pre-preparing the raw material for the synthesis of the medicinal nucleic acid according to claim 5, wherein the bottom of the preparation base (3) is provided with motor grooves (31), the positions and the number of the motor grooves (31) correspond to those of the material tank grooves (32), and stirring assemblies (8) are arranged in the motor grooves (31).
7. The method for pre-preparing the raw material for the synthesis of the medicinal nucleic acid according to claim 6, wherein the preparation tank (5) comprises a tank body (51) and a base (52) arranged at the bottom of the tank body (51), a plurality of positioning holes (53) are arranged at the lower end of the base (52), and positioning columns (33) matched with the positioning holes (53) are arranged on the tank groove (32).
8. The method for preparing the raw material for synthesizing the medicinal nucleic acid according to claim 5, wherein the stirring assembly (8) comprises a connecting seat (84) rotatably installed at the bottom of the base (52), a stirring shaft (85) is fixedly connected to the connecting seat (84), and a plurality of groups of stirring rods (86) are uniformly installed on a shaft rod of the stirring shaft (85) extending into the tank body (51).
9. The method for pre-preparing the raw material for the synthesis of the medicinal nucleic acid according to claim 8, wherein the stirring assembly (8) further comprises a third motor (81) fixedly installed in the motor groove (31), the output end of the third motor (81) is fixedly connected with a driving shaft (82), the driving shaft (82) penetrates through the ingredient base (3) and is fixedly connected with a driving plate (83), and the connecting seat (84) is provided with a driving hole matched with the driving plate (83).
10. The method for preparing the raw material for the synthesis of the medicinal nucleic acid as claimed in claim 5, wherein the feeding assembly (7) comprises a cylindrical tube (71) fixedly arranged on the connecting bracket (4), and a prism tube (72) is arranged at the lower end of the cylindrical tube (71).
CN202210307136.1A 2022-03-25 2022-03-25 Method for preparing raw materials for medicinal nucleic acid synthesis Pending CN114653250A (en)

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Application publication date: 20220624