CN115178213B - Preparation system and preparation process of dexamethasone sodium phosphate - Google Patents
Preparation system and preparation process of dexamethasone sodium phosphate Download PDFInfo
- Publication number
- CN115178213B CN115178213B CN202210815068.XA CN202210815068A CN115178213B CN 115178213 B CN115178213 B CN 115178213B CN 202210815068 A CN202210815068 A CN 202210815068A CN 115178213 B CN115178213 B CN 115178213B
- Authority
- CN
- China
- Prior art keywords
- tank
- valve
- switch valve
- reaction tank
- crystallization
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- 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
- B01J19/18—Stationary reactors having moving elements inside
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D17/00—Separation of liquids, not provided for elsewhere, e.g. by thermal diffusion
- B01D17/02—Separation of non-miscible liquids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D36/00—Filter circuits or combinations of filters with other separating devices
- B01D36/003—Filters in combination with devices for the removal of liquids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
- B01D9/02—Crystallisation from solutions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
Landscapes
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Physics & Mathematics (AREA)
- Thermal Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
Abstract
The invention belongs to the technical field of crystallization, and particularly discloses a preparation system of dexamethasone sodium phosphate, which comprises a condition control system, a reaction tank assembly and a crystallization assembly; the condition control system is connected with the reaction tank assembly and is at least used for providing low-temperature conditions and heat preservation conditions required by the reaction for the reaction tank assembly; the crystallization component is communicated with the reaction tank body through a pipeline and is used for conveying reaction products of the reaction tank component to the crystallization component for crystallization. According to the invention, through multistage standing phase separation, the water phase and the oil phase are thoroughly separated, the product precision of dexamethasone sodium phosphate is improved, in the crystallization process, crystal growth is formed through heat convection of the upper heating block and the lower heating block, the crystal quality is improved, and the storage is convenient.
Description
Technical Field
The invention belongs to the technical field of crystallization, and particularly relates to a preparation system and a preparation process of dexamethasone sodium phosphate.
Background
Dexamethasone sodium phosphate, the chemical name of which is 16α -methyl-11β,17α,21 trihydroxy-9α -fluoropregna-1, 4-diene-3, 20-dione-21-phosphate disodium salt, is an adrenocortical hormone medicine, and has anti-inflammatory, antiallergic, antirheumatic and immunosuppressive effects.
In the prior art, dexamethasone sodium phosphate is mostly stored in a crystal state, but the crystal state and crystallization conditions are not studied, so that the heat resistance of the dexamethasone sodium phosphate is poor and the dexamethasone sodium phosphate is not well stored, and in the preparation process of the dexamethasone sodium phosphate, the water phase and the oil phase are not thoroughly separated, so that the product precision is poor.
Therefore, providing a new preparation system and process of dexamethasone sodium phosphate is a technical problem to be solved by the technicians in the field.
Disclosure of Invention
The invention aims to overcome the defects of poor precision and poor preservation of dexamethasone sodium phosphate in the prior art and provides a preparation system of dexamethasone sodium phosphate.
The invention provides a preparation system of dexamethasone sodium phosphate, which comprises a condition control system, a reaction tank assembly and a crystallization assembly;
the condition control system is connected with the reaction tank assembly and is at least used for providing low-temperature conditions and heat preservation conditions required by the reaction for the reaction tank assembly;
the crystallization component is communicated with the reaction tank body through a pipeline and is used for conveying reaction products of the reaction tank component to the crystallization component for crystallization;
the reaction tank assembly includes: the tank comprises a support and a tank body arranged on the support;
the tank body comprises: the reaction tank, the upper cover and the isolation tank body;
the outside of the reaction tank is provided with a conducting strip, the outside of the conducting strip is provided with a sealed temperature control area formed by measuring around the reaction tank, and the outside of the temperature control area is the inner wall of the tank body; a first inlet is formed in one side of the temperature control area, the first inlet extends to the outside of the reaction tank, a first switch valve is arranged at the first inlet, a first outlet is formed in the other side of the temperature control area, the first outlet extends to the outside of the reaction tank, and a second switch valve is arranged at the first outlet;
a stirring device is arranged in the reaction tank;
the upper cover is positioned at the top of the reaction tank and is respectively provided with a first feeding port, a second feeding port, a third feeding port and a fourth feeding port which are communicated with the reaction tank;
the isolation tank body is positioned at the bottom of the reaction tank, the bottom of the isolation tank body is sealed and hollow, the inside of the isolation tank body is divided into six functional areas from top to bottom, the first functional area is a first standing tank, the second functional area is a first water collecting tank and a first oil phase tank which are arranged side by side, the third functional area is a second standing tank, the fourth functional area is a second oil phase tank and a second water collecting tank which are arranged side by side, the fifth functional area is an active carbon filter layer, and the sixth functional area is a collecting tank;
one side of the first water collection tank is connected to the water collection tank through a thirteenth switching valve through a third outlet;
a fifth charging port is arranged on the tank body shell at one side of the upper part of the second standing tank, a seventh switching valve is arranged at the fifth charging port, and the seventh switching valve is connected with the condition control system through a pipeline;
a fourth outlet is arranged on one side of the second oil phase tank, and the fourth outlet is connected to the oil phase tank through a fourteenth switching valve;
a second outlet is arranged at the collecting tank, an eleventh switching valve is arranged at the second outlet, and the second outlet is connected to the multistage omentum filter through the eleventh switching valve;
the multistage omentum filter is in communication with the crystallization assembly.
The bottom of the reaction tank is provided with a third switching valve, and the third switching valve is connected to the first standing tank through a first standing input pipeline;
the bottom of the first standing tank is provided with a fourth switching valve and a fifth switching valve, the fourth switching valve is connected to the first water collecting tank through a pipeline, and the fifth switching valve is connected to the first oil phase tank through a pipeline;
a sixth switching valve is arranged at the bottom of the first oil phase tank and is connected to the second standing tank through a pipeline;
the bottom of the second standing tank is provided with an eighth switching valve and a ninth switching valve, the eighth switching valve is connected to the second oil phase tank through a pipeline, and the ninth switching valve is connected to the second water collecting tank through a pipeline;
the second water collection tank bottom is provided with tenth ooff valve, tenth ooff valve is connected to the active carbon filter layer, active carbon filter layer bottom is provided with the filter.
The inner wall of the isolation tank body is provided with an inner lining plate, a first supporting plate is arranged between the first functional area and the second functional area, and two sides of the first supporting plate are fixed on the inner lining plate;
a second supporting plate is arranged between the second functional area and the third functional area, and two sides of the second supporting plate are fixed on the inner lining plate;
a third supporting plate is arranged between the third functional area and the fourth functional area, and two sides of the third supporting plate are fixed on the inner lining plate;
a fourth supporting plate is arranged between the fourth functional area and the fifth functional area, and two sides of the fourth supporting plate are fixed on the inner lining plate.
The condition control system comprises an electric cabinet, wherein an isolation substrate is arranged at the upper part of the electric cabinet, a cold storage box is arranged at the upper part of the isolation substrate, and a base is arranged at the upper part of the cold storage box;
a heating fan is arranged at one side of the top of the base; a supporting seat is arranged in the middle of the top of the base, a refrigerating unit is arranged on the upper part of the supporting seat, and the refrigerating unit is connected to the cold accumulation box through a refrigerating pipeline and an electromagnetic valve; a sodium hydroxide solution tank is arranged on the other side of the top of the base;
the sodium hydroxide solution tank charging pipeline is communicated with the seventh switch valve;
the cold accumulation box is communicated with the first switch valve through a cold air pipe and a first interface of the first two-way valve;
the heating fan is communicated with the second port of the first two-way valve through a hot gas pipeline;
the cold accumulation box is communicated with the second switch valve through a return pipeline and a first interface of the second two-way valve, and a second interface of the second two-way valve is communicated with the outside of the reaction tank.
Further, the crystallization component comprises a crystallization tank and an acetone storage tank;
a recovery port is formed in one side of the top of the crystallization tank, a nozzle is arranged in the center of the top of the crystallization tank, a pressurizing device is arranged at the top of the nozzle, and a pressurizing pipe is arranged on one side of the pressurizing device; a discharge hole is formed in the bottom of the crystallization tank and is connected to the crystal collecting tank through a pipeline and a fifteenth switching valve;
the multistage omentum filter is communicated with a first port of a three-way valve through a water phase solution pipeline, the acetone storage tank is communicated with a second port of the three-way valve through a pipeline and a sixteenth switching valve, and a third port of the three-way valve is communicated with the pressurizing device through a mixer and a twelfth switching valve;
the top of the crystallization tank is provided with an upper heating block, the bottom of the crystallization tank is provided with a lower heating block, and heating wires are arranged inside the upper heating block and the lower heating block.
The top of the recycling port is provided with an exhaust valve assembly;
the exhaust valve assembly comprises a valve body and a stroke seat, one end of the valve body is in butt joint with the recovery port, and the stroke seat is arranged at the upper part of the valve body;
the valve body is internally provided with a film pressure plate, a film transversely penetrating through the film pressure plate is embedded in the film pressure plate, and two sides of the film are fixed on a fixed lug in the valve body;
the upper part of the film pressure plate is provided with a shaft lever, the outside of the shaft lever is provided with a spring, the spring is clamped at the joint of the stroke seat and the valve body, a sealing seat is arranged between the stroke seat and the valve body, and the shaft lever penetrates through the sealing seat.
According to a further scheme, one side of the crystallization tank is provided with a temperature controller, and the temperature controller is used for controlling the temperature of the heating wire.
The further scheme is that the first switch valve to the sixteenth switch valve are respectively connected with a control device in the electric cabinet;
metering pumps are respectively arranged at the first feeding port, the second feeding port, the third feeding port, the fourth feeding port and the fifth feeding port.
In a second aspect of the present invention, there is provided a preparation process of dexamethasone sodium phosphate, the preparation process applying the preparation system described above, comprising the following steps:
step 1, preparing dexamethasone phosphate solution:
adding anhydrous tetrahydrofuran into a reaction tank through a first charging port, adding dexamethasone into the reaction tank through a second charging port, stirring, controlling a first two-way valve to be opened, enabling cold air flow at the temperature of minus 70 ℃ in a cold storage box to enter a temperature control zone, enabling the internal temperature of the reaction tank to be reduced to minus 55 ℃, adding pyrophosphoryl chloride into the reaction tank, and stirring; adding pure water for hydrolysis, discharging cold air in the reaction tank, closing an electromagnetic valve on a return pipeline when the cold air is discharged by more than 70%, sending hot air into a temperature control area by a heating fan, simultaneously keeping a second switch valve on, gradually heating the reaction tank to 25-30 ℃, and keeping low-speed stirring for 20-30min to obtain dexamethasone phosphate solution; toluene is added from a third charging port, low-speed stirring is kept for 10-20min, a third switching valve at the bottom of the reaction tank is opened to enable all the solution to flow into the first standing tank, then the third switching valve is closed, and the reaction tank starts the next round of preparation procedure;
standing and phase-separating in the first standing tank, wherein the oil phase is at the upper part, the water phase is at the lower part, a fourth switch valve is opened, the water phase is led into the first water collecting tank, after the water phase is finished, the fourth switch valve is closed, a fifth switch valve is opened, and the oil phase is led into the first oil phase tank;
opening a sixth switch valve, introducing all the oil phase in the first oil phase tank into a second standing tank, opening the seventh switch valve, dripping sodium hydroxide solution into the second standing tank to enable the PH in the second standing tank to be 10-11, standing for phase separation, introducing the water phase into a second water collecting tank by opening an eighth switch valve when the water phase is at the bottom and the oil phase is at the upper part, closing the eighth switch valve after the water phase is collected, opening a ninth switch valve, and collecting the oil phase into the second oil phase tank;
step 4, decoloring and filtering;
opening a tenth switch valve, fully introducing the aqueous phase solution into an active carbon filter layer for decoloration and filtration, and flowing the aqueous phase solution into a collecting tank after decoloration and filtration; opening an eleventh switch valve, and inputting the aqueous phase solution to the multistage omentum filter through a second outlet;
and 5, crystallizing, namely fusing the aqueous phase solution which is subjected to the mesh membrane filter with acetone, spraying the fused aqueous phase solution into a crystallization tank through a nozzle, maintaining the crystallization tank at 40-60 ℃ for 30 minutes, and then heating an upper heating block and a lower heating block to 150-180 ℃ at the same time, and drying and crystallizing.
Compared with the prior art, the invention has the beneficial effects that:
according to the invention, through multistage standing phase separation, the water phase and the oil phase are thoroughly separated, and the product precision of dexamethasone sodium phosphate is improved. In addition, the preparation conditions of firstly cooling and then heating are adopted in the reaction tank, so that the preparation mechanism of dexamethasone sodium phosphate is met, and the product quality is improved. In the crystallization process, the crystal is grown by heat convection of the upper heating block and the lower heating block, so that the crystal quality is improved, and the crystal is convenient to store.
Drawings
The following drawings are illustrative of the invention and are not intended to limit the scope of the invention, in which:
fig. 1: the structure of the invention is schematically shown;
fig. 2: the condition control system is connected with the reaction tank assembly through a schematic diagram;
fig. 3: the structure of the crystallization component is schematically shown.
Detailed Description
The present invention will be further described in detail with reference to the following specific examples, which are given by way of illustration, in order to make the objects, technical solutions, design methods and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
1-3, the invention provides a preparation system of dexamethasone sodium phosphate, which comprises a condition control system, a reaction tank component and a crystallization component; the condition control system is connected with the reaction tank assembly and is used for providing low-temperature conditions and heat preservation conditions required by the reaction for the reaction tank assembly; the crystallization component is communicated with the reaction tank body through a pipeline and is used for conveying reaction products of the reaction tank component to the crystallization component for crystallization;
the reaction tank assembly includes: a support 55 and a can body provided on the support 55;
the tank body comprises: a reaction tank, an upper cover 14 and a separation tank 33;
the outside of the reaction tank is provided with a conducting strip, the outside of the conducting strip is provided with a sealed temperature control zone 22 formed by measuring around the circumference of the reaction tank, and the outside of the temperature control zone 22 is the inner wall of the tank body; a first inlet 23 is formed in one side of the temperature control area 22, the first inlet 23 extends to the outside of the reaction tank, a first switch valve 24 is arranged at the first inlet 23, a first outlet 25 is arranged at the other side of the temperature control area 22, the first outlet 25 extends to the outside of the reaction tank, and a second switch valve 26 is arranged at the first outlet 25;
the inside agitating unit that is provided with of retort, agitating unit include (mixing) shaft 15 and agitator motor 17, and agitator shaft 15 passes through shaft coupling 16 with agitator motor 17 on upper portion of upper cover 14 to be connected.
The upper cover 14 is positioned at the top of the reaction tank, and a first charging port 18, a second charging port 19, a third charging port 20 and a fourth charging port 21 which are communicated with the reaction tank are respectively arranged on the upper cover 14;
the isolation tank body 33 is located at the bottom of the reaction tank, the bottom of the isolation tank body 33 is sealed and hollow, the interior of the isolation tank body 33 is divided into six functional areas from top to bottom, the first functional area is a first standing tank 29, the second functional area is a first water collecting tank 44 and a first oil phase tank 38 which are arranged side by side, the third functional area is a second standing tank 39, the fourth functional area is a second oil phase tank 49 and a second water collecting tank 42 which are arranged side by side, the fifth functional area is an activated carbon filter layer 50, and the sixth functional area is a collecting tank 52;
one side of the first water collection tank 44 is connected to a water collection tank 57 through a thirteenth switching valve 36 via a third outlet 35;
a fifth charging port is arranged on the tank body shell at one side of the upper part of the second standing tank 39, a seventh switch valve 34 is arranged at the fifth charging port, and the seventh switch valve 34 is connected with the condition control system through a pipeline;
a fourth outlet 47 is provided at one side of the second oil phase tank 49, and the fourth outlet 47 is connected to an oil phase tank 56 via a fourteenth switching valve 48;
a second outlet 53 is arranged at the collecting tank 52, an eleventh switch valve 54 is arranged at the second outlet 53, and the second outlet 53 is connected to a multistage omentum filter 58 through the eleventh switch valve 54;
the multi-stage omentum filter 58 is in communication with the crystallization assembly.
In the above, a third switch valve 27 is arranged at the bottom of the reaction tank, and the third switch valve 27 is connected to a first standing tank 29 through a first standing input pipeline 28;
the bottom of the first standing tank 29 is provided with a fourth switch valve 32 and a fifth switch valve 31, the fourth switch valve 32 is connected to the first water collecting tank 44 through a pipeline, and the fifth switch valve 31 is connected to the first oil phase tank 38 through a pipeline;
a sixth switching valve 41 is arranged at the bottom of the first oil phase tank 38, and the sixth switching valve 41 is connected to the second standing tank 39 through a pipeline;
an eighth switching valve 40 and a ninth switching valve 45 are arranged at the bottom of the second standing tank 39, the eighth switching valve 40 is connected to the second oil phase tank 49 through a pipeline, and the ninth switching valve 45 is connected to the second water collecting tank 42 through a pipeline;
a tenth on-off valve 46 is provided at the bottom of the second water collecting tank 42, the tenth on-off valve 46 is connected to the activated carbon filter layer 50, and a filter plate 51 is provided at the bottom of the activated carbon filter layer 50.
In the above, the inner wall of the insulation tank 33 is provided with an inner lining plate, a first support plate is arranged between the first functional area and the second functional area, and two sides of the first support plate are fixed on the inner lining plate;
a second supporting plate is arranged between the second functional area and the third functional area, and two sides of the second supporting plate are fixed on the inner lining plate;
a third supporting plate is arranged between the third functional area and the fourth functional area, and two sides of the third supporting plate are fixed on the inner lining plate;
a fourth support plate 43 is arranged between the fourth functional area and the fifth functional area, and two sides of the fourth support plate 43 are fixed on the inner lining plate.
As shown in fig. 2, the condition control system comprises an electric cabinet 1, wherein a control device is arranged in the electric cabinet 1, an isolation substrate 2 is arranged at the upper part of the electric cabinet 1, a cold storage box 3 is arranged at the upper part of the isolation substrate 2, and a base 4 is arranged at the upper part of the cold storage box 3;
a heating fan 5 is arranged at one side of the top of the base 4; a supporting seat 6 is arranged in the middle of the top of the base 4, a refrigerating unit 9 is arranged at the upper part of the supporting seat 6, and the refrigerating unit is connected to the cold accumulation box 3 through a refrigerating pipeline 8 and an electromagnetic valve 7; a sodium hydroxide solution tank is arranged on the other side of the top of the base 4;
the sodium hydroxide solution tank charging pipeline is communicated with the seventh switch valve 34;
the cold accumulation box 3 is communicated with the first switch valve 24 through a cold air pipe 12 and a first interface of a first two-way valve 13;
the heating fan 5 is communicated with a second port of the first two-way valve 13 through a hot gas pipeline 10;
the cold accumulation tank 3 is communicated with the second switch valve 26 through the return pipeline 11 and a first port of the second two-way valve 37, and a second port of the second two-way valve 37 is communicated with the outside of the reaction tank.
As shown in fig. 3, the crystallization assembly includes a crystallization tank 78 and an acetone storage tank 81;
a recovery port 67 is formed in one side of the top of the crystallization tank 78, a nozzle 65 is arranged in the center of the top of the crystallization tank 78, a pressurizing device 63 is arranged at the top of the nozzle 65, and a pressurizing pipe 64 is arranged on one side of the pressurizing device 63; a discharge hole 77 is formed in the bottom of the crystallization tank 78, and the discharge hole 77 is connected to a crystal collecting tank 80 through a pipeline and a fifteenth switching valve 76;
the multistage omentum filter 58 is communicated with a first port of a three-way valve through a water phase solution pipeline 59, the acetone storage tank 81 is communicated with a second port of the three-way valve through a pipeline and a sixteenth switching valve 82, and a third port of the three-way valve is communicated with the pressurizing device 63 through a mixer 61 and a twelfth switching valve 62;
the top of the crystallization tank 78 is provided with an upper heating block 66, the bottom of the crystallization tank is provided with a lower heating block 75, and heating wires are arranged inside the upper heating block 66 and the lower heating block 75.
In the above, the top of the recovery port 67 is provided with an exhaust valve assembly;
the exhaust valve assembly comprises a valve body 72 and a stroke seat 70, one end of the valve body 72 is in butt joint with the recovery port 67, and the stroke seat 70 is arranged at the upper part of the valve body 72;
a film pressure plate 71 is arranged in the valve body 72, a film 74 transversely penetrating through the film pressure plate 71 is embedded in the film pressure plate 71, and two sides of the film 74 are fixed on a fixed lug in the valve body 72;
the upper portion of the film pressure plate 71 is provided with a shaft lever 69, the outside of the shaft lever 69 is provided with a spring 68, the spring 68 is clamped at the joint of the stroke seat 70 and the valve body 72, a sealing seat is arranged between the stroke seat 70 and the valve body 72, and the shaft lever 69 penetrates through the sealing seat. One side of the crystallization tank 78 is provided with a temperature controller 79, and the temperature controller 79 is used for controlling the temperature of the heating wire.
For better implementation, the first to sixteenth switching valves 24 to 82 are respectively connected with a control device in the electric cabinet 1; metering pumps are respectively arranged at the first feeding port 18, the second feeding port 19, the third feeding port 20, the fourth feeding port 21 and the fifth feeding port.
In a second aspect of the invention, there is provided a process for preparing dexamethasone sodium phosphate, comprising the following steps:
1: preparation of dexamethasone phosphate solution
200L of anhydrous tetrahydrofuran is added into a reaction tank through a first charging port 18, 100mol of dexamethasone is added into the reaction tank through a second charging port 19, a stirring motor 17 is started, and the motor drives a stirring shaft 15 to stir at a low speed for 25 minutes through a coupling 16, so that the mixture is fully dispersed; the first two-way valve 13 is controlled to be opened, cold air with the temperature of minus 70 ℃ in the cold accumulation box 3 flows through the cold air pipe 12, the first two-way valve 13, the first switch valve 24 and the first inlet 23 to enter the temperature control area 22, low-temperature gas in the temperature control area 22 refrigerates in the reaction tank through the conducting sheet, the internal temperature of the reaction tank is reduced to minus 55 ℃ and kept unchanged in the low-temperature environment with the temperature of minus 55 ℃, 300mol of pyrophosphoryl chloride is added into the reaction tank, the stirring is kept at a low speed for 80min, 100L of pure water is added for hydrolysis after the completion, the second switch valve 26 and the second two-way valve 37 at the first outlet 25 are opened in the hydrolysis process, cold air is injected into the cold accumulation box through the return pipeline 11, when the cold air is discharged by more than 70%, the electromagnetic valve on the return pipeline 11 is closed, the first two-way valve is controlled to be opened to be connected with the hot air pipeline, the heating fan 5 enters hot air into the temperature control area 22 through the hot air pipeline 10, the two-way valve first switch valve 24 and the first inlet 23, meanwhile, the second switch valve 26 at the first outlet 25 is kept open, so that air flow in the temperature control area 22 flows, the cold air is discharged completely, then the second switch valve 26 is closed for heat preservation, so that the reaction tank is gradually heated to 28 ℃, and the dexamethasone phosphate solution is obtained after stirring at a low speed for 25 min.
150L of toluene was then added from the third feed port 20, stirring was maintained at a low speed for 15 minutes, then the third on-off valve 27 at the bottom of the reaction tank was opened so that the solution entirely flowed into the first stationary tank 29, then the third on-off valve 27 was closed, the reaction tank started the next round of preparation process,
2: standing for phase separation for the first time, and collecting an oil phase;
standing 2H in a first standing tank 29 to split phases, wherein an oil phase is at the upper part, a water phase is at the lower part, then opening a fourth switching valve 32 to guide the water phase into a first water collecting tank 44, closing the fourth switching valve 32 after finishing the water phase, opening a fifth switching valve 31 to guide the oil phase into a first oil phase tank 38;
3: standing for the second time for phase separation, and collecting a water phase;
opening a sixth switch valve 41 at the bottom of the first oil phase tank 38, introducing all the oil phase in the first oil phase tank into the second standing tank 39, opening a seventh switch valve 34 at the upper part of the second standing tank 39, dripping sodium hydroxide solution into the regulating tank to enable the PH in the regulating tank to be 10.5, then standing in the regulating tank for 1h to perform phase separation, wherein the water phase is at the bottom, the oil phase is at the upper part, opening an eighth switch valve 40 at the bottom of the regulating tank, introducing the water phase into a second water collecting tank 42, closing the eighth switch valve 40 after the water phase is collected, opening a ninth switch valve 45, and collecting the oil phase into a second oil phase tank 49;
4: decoloring and filtering to obtain a filtrate,
opening a tenth switch valve 46 at the bottom of the second water collecting tank 42, introducing all the aqueous phase solution into an active carbon filter layer 50 for decoloration and filtration, and flowing the decolored and filtered aqueous phase solution into a collecting tank 52; opening the eleventh on-off valve 54 at the collection tank 52 to input the aqueous phase solution to the multistage mesh membrane filter 58 via the second outlet;
5: crystallizing, the aqueous solution and acetone are fused by the omentum filter 58 and then pass through the mixer 61, the twelfth switch valve 62 and the pressurizing device 63, one side of the pressurizing device 63 is provided with the pressurizing pipe 64, the aqueous solution and acetone are fused and then are sprayed into the crystallizing tank 78 by the high-pressure gas at the pressurizing device 63 through the nozzle 65, so that the aqueous solution and the acetone are fully dispersed and fused, the upper heating wire and the lower heating wire at the upper part and the lower part of the crystallizing tank are simultaneously opened to heat the upper heating block and the lower heating block respectively, the upper heating block and the lower heating block are simultaneously heated to 50 ℃, the upper heating block and the lower heating block are subjected to heat convection to form crystal growth, the crystal growth is kept for 30 minutes, and then the upper heating block and the lower heating block are simultaneously heated to 165 ℃, and drying crystallization is carried out.
The foregoing description of embodiments of the invention has been presented for purposes of illustration and description, and is not intended to be exhaustive or limited to the embodiments disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the various embodiments described. The terminology used herein was chosen in order to best explain the principles of the embodiments, the practical application, or the technical improvements in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.
Claims (7)
1. The preparation system of dexamethasone sodium phosphate is characterized by comprising a condition control system, a reaction tank assembly and a crystallization assembly;
the condition control system is connected with the reaction tank assembly and is at least used for providing low-temperature conditions and heat preservation conditions required by the reaction for the reaction tank assembly;
the crystallization component is communicated with the reaction tank body through a pipeline and is used for conveying reaction products of the reaction tank component to the crystallization component for crystallization;
the reaction tank assembly includes: a support (55) and a tank body arranged on the support (55);
the tank body comprises: a reaction tank, an upper cover (14) and an isolation tank body (33); top part
The outside of the reaction tank is provided with a conducting strip, the outside of the conducting strip is provided with a sealed temperature control area (22) formed by measuring around the circumference of the reaction tank, and the outside of the temperature control area (22) is the inner wall of the tank body; a first inlet (23) is formed in one side of the temperature control area (22), the first inlet (23) extends to the outside of the reaction tank, a first switch valve (24) is arranged at the first inlet (23), a first outlet (25) is formed in the other side of the temperature control area (22), the first outlet (25) extends to the outside of the reaction tank, and a second switch valve (26) is arranged at the first outlet (25);
a stirring device is arranged in the reaction tank;
the upper cover (14) is positioned at the top of the reaction tank, and a first feeding port (18), a second feeding port (19), a third feeding port (20) and a fourth feeding port (21) which are communicated with the reaction tank are respectively arranged on the upper cover (14);
the isolation tank body (33) is positioned at the bottom of the reaction tank, the bottom of the isolation tank body (33) is sealed, the inside of the isolation tank body (33) is hollow, the isolation tank body (33) is divided into six functional areas from top to bottom, the first functional area is a first standing tank (29), the second functional area is a first water collecting tank (44) and a first oil phase tank (38) which are arranged side by side, the third functional area is a second standing tank (39), the fourth functional area is a second oil phase tank (49) and a second water collecting tank (42) which are arranged side by side, the fifth functional area is an active carbon filter layer (50), and the sixth functional area is a collecting tank (52);
one side of the first water collection tank (44) is connected to a water collection tank (57) through a thirteenth switch valve (36) through a third outlet (35);
a fifth charging port is arranged on the tank body shell at one side of the upper part of the second standing tank (39), a seventh switching valve (34) is arranged at the fifth charging port, and the seventh switching valve (34) is connected with the condition control system through a pipeline;
a fourth outlet (47) is arranged on one side of the second oil phase tank (49), and the fourth outlet (47) is connected to an oil phase tank (56) through a fourteenth switch valve (48);
a second outlet (53) is arranged at the collecting tank (52), an eleventh switch valve (54) is arranged at the second outlet (53), and the second outlet (53) is connected to a multistage mesh membrane filter (58) through the eleventh switch valve (54);
the multistage omentum filter (58) is in communication with the crystallization assembly;
the condition control system comprises an electric cabinet (1), wherein an isolation substrate (2) is arranged at the upper part of the electric cabinet (1), a cold storage box (3) is arranged at the upper part of the isolation substrate (2), and a base (4) is arranged at the upper part of the cold storage box (3);
a heating fan (5) is arranged at one side of the top of the base (4); a supporting seat (6) is arranged in the middle of the top of the base (4), a refrigerating unit (9) is arranged on the upper part of the supporting seat (6), and the refrigerating unit is connected to the cold accumulation box (3) through a refrigerating pipeline (8) and an electromagnetic valve (7); a sodium hydroxide solution tank is arranged on the other side of the top of the base (4);
the sodium hydroxide solution tank charging pipeline is communicated with the seventh switch valve (34);
the cold accumulation box (3) is communicated with the first switch valve (24) through a cold air pipe (12) and a first interface of the first two-way valve (13);
the heating fan (5) is communicated with a second interface of the first two-way valve (13) through a hot gas pipeline (10);
the cold accumulation box (3) is communicated with the second switch valve (26) through a return pipeline (11) and a first interface of a second two-way valve (37), and a second interface of the second two-way valve (37) is communicated with the outside of the reaction tank;
the crystallization assembly comprises a crystallization tank (78) and an acetone storage tank (81);
a recovery port (67) is formed in one side of the top of the crystallization tank (78), a nozzle (65) is arranged in the center of the top of the crystallization tank (78), a pressurizing device (63) is arranged at the top of the nozzle (65), and a pressurizing pipe (64) is arranged on one side of the pressurizing device (63); a discharge hole (77) is formed in the bottom of the crystallization tank (78), and the discharge hole (77) is connected to a crystal collecting tank (80) through a pipeline and a fifteenth switch valve (76);
the multistage omentum filter (58) is communicated with a first port of a three-way valve through a water phase solution pipeline (59), the acetone storage tank (81) is communicated with a second port of the three-way valve through a pipeline and a sixteenth switch valve (82), and a third port of the three-way valve is communicated with the pressurizing device (63) through a mixer (61) and a twelfth switch valve (62);
the top of the crystallization tank (78) is provided with an upper heating block (66), the bottom of the crystallization tank (78) is provided with a lower heating block (75), and heating wires are arranged inside the upper heating block (66) and the lower heating block (75).
2. The preparation system of dexamethasone sodium phosphate as claimed in claim 1, wherein a third switch valve (27) is arranged at the bottom of the reaction tank, and the third switch valve (27) is connected to the first standing tank (29) through a first standing input pipeline (28 top);
a fourth switching valve (32) and a fifth switching valve (31) are arranged at the bottom of the first standing tank (29), the fourth switching valve (32) is connected to the first water collecting tank (44) through a pipeline, and the fifth switching valve (31) is connected to the first oil phase tank (38) through a pipeline;
a sixth switch valve (41) is arranged at the bottom of the first oil phase tank (38), and the sixth switch valve (41) is connected to the second standing tank (39) through a pipeline;
an eighth switching valve (40) and a ninth switching valve (45) are arranged at the bottom of the second standing tank (39), the eighth switching valve (40) is connected to the second oil phase tank (49) through a pipeline, and the ninth switching valve (45) is connected to the second water collecting tank (42) through a pipeline;
the bottom of the second water collecting tank (42) is provided with a tenth switch valve (46), the tenth switch valve (46) is connected to the activated carbon filter layer (50), and the bottom of the activated carbon filter layer (50) is provided with a filter plate (51).
3. The preparation system of dexamethasone sodium phosphate as claimed in claim 1, wherein an inner wall of the isolation tank (33) is provided with an inner lining plate, a first supporting plate is arranged between the first functional area and the second functional area, and two sides of the first supporting plate are fixed on the inner lining plate;
a second supporting plate is arranged between the second functional area and the third functional area, and two sides of the second supporting plate are fixed on the inner lining plate;
a third supporting plate is arranged between the third functional area and the fourth functional area, and two sides of the third supporting plate are fixed on the inner lining plate;
a fourth supporting plate (43) is arranged between the fourth functional area and the fifth functional area, and two sides of the fourth supporting plate (43) are fixed on the inner lining plate.
4. The dexamethasone sodium phosphate preparation system as in claim 1, wherein the top of the recovery port (67) is provided with an exhaust valve assembly;
the exhaust valve assembly comprises a valve body (72) and a stroke seat (70), one end of the valve body (72) is in butt joint with the recovery port (67), and the stroke seat (70) is arranged at the upper part of the valve body (72);
a film pressure plate (71) is arranged in the valve body (72), a film (74) transversely penetrating through the film pressure plate (71) is embedded in the film pressure plate (71), and two sides of the film (74) are fixed on a fixed lug in the valve body (72);
the thin film pressure plate (71) upper portion is provided with axostylus axostyle (69), the outside of axostylus axostyle (69) is provided with spring (68), spring (68) card are in the junction of stroke seat (70) and valve body (72), are provided with the seal seat between stroke seat (70) and valve body (72), axostylus axostyle (69) run through the seal seat.
5. The dexamethasone sodium phosphate preparation system as claimed in claim 4, wherein a temperature controller (79) is arranged at one side of the crystallization tank (78), and the temperature controller (79) is used for controlling the temperature of the heating wire.
6. The dexamethasone sodium phosphate preparation system according to any one of claims 1-5, characterized in that the first switch valve (24) to the sixteenth switch valve (82) are respectively connected with a control device in the electric cabinet (1);
metering pumps are respectively arranged at the first feeding port (18), the second feeding port (19), the third feeding port (20), the fourth feeding port (21) and the fifth feeding port.
7. A process for preparing dexamethasone sodium phosphate, characterized in that the process employs the preparation system according to claim 6, comprising the following steps:
step 1, preparing dexamethasone phosphate solution:
adding anhydrous tetrahydrofuran into a reaction tank through a first charging port (18), adding dexamethasone into the reaction tank through a second charging port (19), stirring, controlling a first two-way valve (13) to be opened, enabling cold air flow at the temperature of minus 70 ℃ in a cold accumulation box (3) to enter a temperature control zone (22), enabling the internal temperature of the reaction tank to be reduced to minus 55 ℃, adding pyrophosphoryl chloride into the reaction tank, and stirring; adding pure water for hydrolysis, discharging cold air in the reaction tank, closing an electromagnetic valve on a return pipeline (11) when the cold air is discharged by more than 70%, sending hot air into a temperature control area (22) by a heating fan (5), simultaneously keeping a second switch valve (26) open, gradually heating the reaction tank to 25-30 ℃, and keeping low-speed stirring for 20-30min to obtain dexamethasone phosphate solution; toluene is added from a third feeding port (20), stirring is kept at a low speed for 10-20min, a third switching valve (27) at the bottom of the reaction tank is opened to enable all the solution to flow into a first standing tank (29), then the third switching valve (27) is closed, and the reaction tank starts the next round of preparation procedure;
step 2, standing for phase separation for the first time, and collecting an oil phase;
standing and phase-separating in a first standing tank (29), wherein an oil phase is at the upper part, a water phase is at the lower part, a fourth switching valve (32) is opened, the water phase is led into a first water collecting tank (44), after the water phase is finished, the fourth switching valve (32) is closed, a fifth switching valve (31) is opened, and the oil phase is led into a first oil phase tank (38);
step 3, standing for phase separation for the second time, and collecting a water phase;
opening a sixth switch valve (41), introducing all the oil phase in the first oil phase tank (38) into the second standing tank (39), opening a seventh switch valve (34), dripping sodium hydroxide solution into the second standing tank (39) to enable the PH in the second standing tank (39) to be 10-11, standing for phase separation, introducing the water phase into the second water collecting tank (42), closing the eighth switch valve (40) after the water phase is collected, opening a ninth switch valve (45), and collecting the oil phase into the second oil phase tank (49);
step 4, decoloring and filtering;
opening a tenth switch valve (46), leading all the aqueous phase solution into an active carbon filter layer (50) for decoloration and filtration, and flowing the decolored and filtered aqueous phase solution into a collecting tank (52); opening an eleventh switch valve (54) and inputting the aqueous phase solution to the multistage mesh membrane filter (58) through a second outlet;
and 5, crystallizing, namely, fusing the aqueous phase solution passing through the omentum filter (58) with acetone, spraying the fused aqueous phase solution into a crystallization tank (78) through a nozzle (65), maintaining the crystallization tank (78) to 40-60 ℃ for 30 minutes, and then heating an upper heating block and a lower heating block to 150-180 ℃ at the same time, and drying and crystallizing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210815068.XA CN115178213B (en) | 2022-07-11 | 2022-07-11 | Preparation system and preparation process of dexamethasone sodium phosphate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210815068.XA CN115178213B (en) | 2022-07-11 | 2022-07-11 | Preparation system and preparation process of dexamethasone sodium phosphate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115178213A CN115178213A (en) | 2022-10-14 |
| CN115178213B true CN115178213B (en) | 2023-06-27 |
Family
ID=83517672
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210815068.XA Active CN115178213B (en) | 2022-07-11 | 2022-07-11 | Preparation system and preparation process of dexamethasone sodium phosphate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115178213B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115057904B (en) * | 2022-07-11 | 2023-06-27 | 西安国康瑞金制药有限公司 | Production process and production device of betamethasone |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112691403A (en) * | 2020-12-14 | 2021-04-23 | 安徽国星生物化学有限公司 | 4-cyanopyridine continuous evaporation crystallization device and method |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4513264B2 (en) * | 2002-02-22 | 2010-07-28 | 三菱化学株式会社 | Method for producing nitride single crystal |
| JP4085870B2 (en) * | 2003-04-02 | 2008-05-14 | 株式会社日立ハイテクサイエンスシステムズ | Microstructure drying method and apparatus and system |
| CN1318442C (en) * | 2005-07-04 | 2007-05-30 | 天津大学<Del/> | Dexamethasone sodium phosphate crystal form and its crystallization preparation method |
| WO2010084681A1 (en) * | 2009-01-23 | 2010-07-29 | 日本碍子株式会社 | Group iiib nitride crystal manufacturing method |
| CN103949083B (en) * | 2014-05-07 | 2016-04-20 | 无锡市张华医药设备有限公司 | A kind of crystallizing tank |
| CN106894465B (en) * | 2015-12-17 | 2020-08-14 | 青岛海尔滚筒洗衣机有限公司 | Household wastewater recycling system and wastewater recycling method |
| CN105582689A (en) * | 2016-03-10 | 2016-05-18 | 黄斌 | Reaction crystallizer for crystallization |
| CN109134581A (en) * | 2017-08-15 | 2019-01-04 | 宁应 | Three water dexamethasone sodium phosphate compounds of one kind and its drug combination preparation |
| CN207221920U (en) * | 2017-09-06 | 2018-04-13 | 泉州建邦涂料有限公司 | A kind of automatic temperature-controlled pressure control reaction kettle |
| CN108771882A (en) * | 2018-06-29 | 2018-11-09 | 南京钰博科信新材料有限公司 | A kind of automation chemical industry solutions crystallizer |
| CN209378983U (en) * | 2018-10-31 | 2019-09-13 | 江西大凯新材料有限公司 | A kind of process units of high-end architectural waterproof material methyl sodium silanolate |
| CN209554837U (en) * | 2019-02-25 | 2019-10-29 | 高林顺 | A kind of stewing process device of multistage containing oil-polluted water |
| CN210065724U (en) * | 2019-04-03 | 2020-02-14 | 李晓影 | Microorganism inspection extractor for water-insoluble drugs |
| CN110917645A (en) * | 2019-12-16 | 2020-03-27 | 安徽牧洋油脂有限公司 | Fatty acid steam separation recovery unit for grease production |
| CN213433060U (en) * | 2020-09-07 | 2021-06-15 | 广州德程机电设备有限公司 | Controllable crystallizer |
| CN112047991A (en) * | 2020-09-11 | 2020-12-08 | 西安国康瑞金制药有限公司 | Method for efficiently removing dexamethasone sodium phosphate crystal water |
| CN213555397U (en) * | 2020-10-15 | 2021-06-29 | 河北明吉化工科技有限公司 | Forced circulation evaporation crystallization device |
| CN112094311B (en) * | 2020-10-16 | 2022-04-08 | 西安国康瑞金制药有限公司 | Process for preparing dexamethasone sodium phosphate by one-step method |
| CN214485750U (en) * | 2020-12-11 | 2021-10-26 | 永兴鹏琨环保有限公司 | Pyrolysis oil separation system |
| CN215741893U (en) * | 2021-05-27 | 2022-02-08 | 翔鹭化纤（海城）有限公司 | Pre-crystallizer hot air circulating device |
| CN215427437U (en) * | 2021-07-30 | 2022-01-07 | 江苏金马油脂科技发展有限公司 | Oleic acid separator |
| CN114182341B (en) * | 2021-12-22 | 2022-10-18 | 季华实验室 | High-purity crystal growth system and method |
-
2022
- 2022-07-11 CN CN202210815068.XA patent/CN115178213B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112691403A (en) * | 2020-12-14 | 2021-04-23 | 安徽国星生物化学有限公司 | 4-cyanopyridine continuous evaporation crystallization device and method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115178213A (en) | 2022-10-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN115178213B (en) | Preparation system and preparation process of dexamethasone sodium phosphate | |
| CN109734582B (en) | Production process of sodium acetate | |
| CN107694403A (en) | Heating water bath soybean peptide nutrient solution mixed stirring device | |
| CN115245807A (en) | Reaction kettle with purification structure for adenosine diphosphate preparation and preparation method thereof | |
| CN109646987B (en) | Continuous feeding and discharging high-vacuum organic micromolecule purifying special equipment | |
| CN110102234A (en) | A kind of light reaction production equipment | |
| CN204911487U (en) | High -efficient general many functional response cauldron device | |
| CN115057904B (en) | Production process and production device of betamethasone | |
| CN102416205A (en) | Dry type plasma thawing instrument | |
| CN109894057A (en) | A kind of thermostatic type liquid chemical reaction unit | |
| CN207405181U (en) | The enzymatic isolation method of a kind of retort and its composition prepares the process units of Tagatose | |
| CN207951383U (en) | A kind of vacuum sealing retort | |
| CN215087091U (en) | Low-temperature reaction device for preparing graphene oxide | |
| CN206731133U (en) | Reactor and chemical reaction system | |
| CN212819919U (en) | High-efficient cooling system of digester | |
| CN210796299U (en) | Novel extraction equipment of sisal hemp saponin | |
| CN208512543U (en) | A kind of reaction kettle with cleaning function | |
| CN220861479U (en) | Biphenyl oxidation reaction synthesizer | |
| CN217450150U (en) | Mixing apparatus is used in production of polyolefin APAO hot melt adhesive | |
| CN212818232U (en) | Recrystallization refining device | |
| CN219722907U (en) | 3,5, 6-trichloropyridine-2-sodium phenolate synthesizer | |
| CN215841709U (en) | Turnover crystallization reaction kettle for mesotrione | |
| CN215901757U (en) | A multi-functional reation kettle for medicine pilot scale | |
| CN217856095U (en) | Liquid medicine stirring device | |
| CN213050564U (en) | Double-layer glass reaction kettle |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |