CN114195770B - Preparation method and device of posaconazole - Google Patents
Preparation method and device of posaconazole Download PDFInfo
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- CN114195770B CN114195770B CN202111651018.4A CN202111651018A CN114195770B CN 114195770 B CN114195770 B CN 114195770B CN 202111651018 A CN202111651018 A CN 202111651018A CN 114195770 B CN114195770 B CN 114195770B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Abstract
The invention belongs to the technical field of posaconazole preparation, and particularly relates to a preparation method and device of posaconazole; the device comprises a frame assembly, wherein a crude product dissolving device, a mixed solution decoloring device and a solution crystallization device are arranged on the frame assembly, the mixed solution decoloring device comprises an active carbon decoloring cylinder, a hollow rotating rod is rotationally connected to the active carbon decoloring cylinder, the lower end of the hollow rotating rod is connected with a connecting disc hollow rotating rod, the outer circular surface of the hollow rotating rod is provided with a spiral blade, the lower end of the active carbon decoloring cylinder is also provided with a waste discharge pipe, and the upper end of the active carbon decoloring cylinder is connected with an active carbon feeding machine; according to the posaconazole refining method disclosed by the invention, through the designed mixed liquid decoloring device, invalid activated carbon can be automatically discharged after each pair of mixed liquid with a set volume is decolored, and then new activated carbon particles are automatically subjected to adsorption decoloring under the action of the new activated carbon particles, so that the complete adsorption decoloring of all the mixed liquid can be effectively ensured, and the purity of the posaconazole obtained through the whole refining is effectively ensured.
Description
Technical Field
The invention belongs to the technical field of posaconazole preparation, and particularly relates to a preparation method and device of posaconazole.
Background
Posaconazole is a newly discovered second-generation triazole antifungal drug at present, and is favored because of the characteristics of broad spectrum, high efficiency and low toxicity. The posaconazole organic compound is used as a medicament for clinical application, and has very high purity, and various impurities in the medicinal compound are controlled below pharmacopoeia standards, so that the posaconazole organic compound accords with the marketing standard and is a complex and fine process. The posaconazole has a complex structure, 4 chiral centers are involved in the molecule, a plurality of steps of chemical reactions are needed to obtain the compound, and a series of impurities are introduced in the synthesis process, wherein the steps comprise: unreacted complete intermediate; impurities carried in the raw materials and intermediates; impurities generated by side reactions occur during the synthesis process; intermediate and posaconazole. Therefore, the crude product synthesized by posaconazole needs to be refined and purified before being used for medicines.
The invention patent with the application number of CN2019111374701 discloses a refining method of posaconazole, which comprises the following steps: dissolving the crude posaconazole product in a mixed solvent of ethyl acetate and acetone to fully dissolve the posaconazole; adding active carbon for decoloring, filtering, cooling filtrate for crystallization, and growing crystals; the filtered solid was filtered and washed with acetone and dried in vacuo to give refined posaconazole. Although the method for refining posaconazole disclosed by the invention can realize the purification processing of a posaconazole crude product, the purity of posaconazole can reach more than 99.9%, the activated carbon decolorization process in the method is particularly important, the activated carbon needs to be replaced in time after being used for a period of time, otherwise, activated carbon particles lose the adsorption decolorization effect, and the method is limited by factors of equipment, so that the activated carbon needs to be replaced continuously in the decolorization process in the process of realizing the industrialized posaconazole, and the refining efficiency of the whole posaconazole is greatly reduced. Therefore, in order to solve the defects in the existing posaconazole refining process, the application provides a preparation method and device of posaconazole to solve the defects.
Disclosure of Invention
The invention aims at overcoming the defect that the existing posaconazole refining process is limited by equipment, and active carbon is required to be replaced by continuously interrupting the decoloring process, so that the whole posaconazole refining efficiency is greatly reduced, and the application provides a posaconazole preparation method and device.
The invention is realized by the following technical scheme:
a method for preparing posaconazole, comprising the following steps:
1) Injecting a solvent into the dissolution tank body, quantitatively putting the crude posaconazole product into the solvent through a crude product feeding machine, and rapidly dissolving the crude posaconazole product under the action of a stirring motor;
2) Introducing the dissolved mixed solution into an activated carbon decoloring cylinder, allowing the mixed solution to enter the lower end of the activated carbon decoloring cylinder along a hollow rotating rod, then allowing the mixed solution to flow upwards along a spiral blade, repeatedly contacting with activated carbon particles in the flowing process, adsorbing and decoloring, and replacing 0.6-1.4kg of activated carbon after decoloring every 20-30L of mixed solution;
3) Introducing the filtrate after adsorption and decolorization into a crystallization kettle for cooling, crystallizing at the temperature of-2-4 ℃, and separating the fully crystallized material into crystal liquid;
4) Washing the separated crystal, and vacuum drying after washing to obtain the refined posaconazole.
Preferably, the solvent is one or more of ethyl acetate and acetone.
Preferably, the temperature at which the crude posaconazole product is dissolved is 26-32 ℃.
The preparation device used in the posaconazole preparation method is equipment in the steps 1-3, and comprises a frame assembly, and is characterized in that a crude product dissolving device, a mixed liquid decoloring device and a solution crystallization device are sequentially arranged at the upper end of the frame assembly, and a control box is further arranged at the front end of the frame assembly;
the crude product dissolving device comprises a dissolving tank body, a tank body flange is connected to an upper end opening of the dissolving tank body, a tank body cover is connected to the tank body flange through a fastening bolt, a crude product feeding machine is arranged at one end of the tank body cover, a solvent injection pipe is arranged on the tank body cover at the opposite side of the crude product feeding machine, a stirring motor is arranged at the center of the upper surface of the tank body cover, a stirring shaft extending into the dissolving tank body is connected to an output shaft of the stirring motor, a plurality of groups of stirring rods are connected to the upper end of the stirring shaft, a turning blade is connected to the lower end of the stirring shaft, vertical guide strips are connected to the left end and the right end of the inner wall of the dissolving tank body, a filter screen frame is arranged at the lower end of the dissolving tank body, a filter screen is paved on the upper surface of the filter screen frame, limit ports matched with the guide strips are formed at two ends of the filter screen frame, a round hole penetrating through the stirring shaft is formed in the center of the filter screen frame, a supporting disc is arranged on the stirring shaft below the filter screen frame, a first infusion tube is connected to the lower end of the dissolving tank body, a first infusion tube is connected to the first infusion tube is arranged close to the first infusion tube, and an infusion tube is arranged at the upper end of the infusion tube;
the mixed liquid decoloring device comprises an activated carbon decoloring cylinder, wherein an upper end opening of the activated carbon decoloring cylinder is connected with a cylinder cover through a flange, the end part of a first infusion tube is connected with the center of the cylinder cover, a sealing bearing is arranged on the inner wall of the center of the cylinder cover, a hollow rotating rod is rotationally connected with the sealing bearing, a connecting disc is connected with the center of the lower end opening of the hollow rotating rod through a plurality of connecting rods arranged in the circumferential direction, a rotating motor is arranged at the lower end of the activated carbon decoloring cylinder, an output shaft of the rotating motor stretches into the bottom of an inner cavity of the activated carbon decoloring cylinder to be connected with the connecting disc, a spiral blade attached to the inner wall of the activated carbon cylinder is arranged on the outer circular surface of the hollow rotating rod, a waste discharge pipe is further arranged at the lower end of the activated carbon decoloring cylinder, a sealing valve is arranged on the waste discharge pipe, a second infusion tube is further connected with an activated carbon feeding machine, and a second infusion pump is arranged on the second infusion tube;
the solution crystallization device comprises a crystallization kettle, a cooling medium jacket is arranged on the outer surface of the crystallization kettle, an inlet pipe and a discharge pipe are respectively arranged at the upper end and the lower end of the cooling medium jacket, a driving motor is arranged at the top end of the crystallization kettle, an output shaft of the driving motor stretches into the crystallization kettle, a rotating shaft is connected to the lower end of the driving motor, a scraping plate attached to the inner wall of the crystallization kettle is connected to the lower end of the rotating shaft, a discharge pipe is connected to the lower end of the crystallization kettle, a material valve is arranged on the discharge pipe, and a crystal liquid separation device is connected to the lower end of the discharge pipe.
As the concrete setting of above-mentioned scheme, brilliant liquid separator is including the pay-off barrel that the slope set up, and the interlude of pay-off barrel is connected with the lower extreme of arranging the material pipe, the terminal surface of pay-off barrel is provided with separating motor, separating motor's output shaft stretches into the end connection in the pay-off barrel has the separation spiral leaf, and has seted up a large amount of waterlogging caused by excessive rainfall holes on separating the surface of spiral leaf, the lower slope end of pay-off barrel is connected with the fluid-discharge tube, the last slope end of pay-off barrel is connected with arranges the transistor.
As a further arrangement of the scheme, the upper end of the liquid discharge pipe is also provided with a filter screen layer.
As a further arrangement of the scheme, the outer side face of the dissolution tank body is also provided with a heating heat-preserving jacket, and the upper end and the lower end of the heating heat-preserving jacket are respectively connected with a heat medium inlet pipe and a heat medium outlet pipe.
As a further arrangement of the scheme, a plurality of groups of stirring rods are also arranged at the upper end of the rotating shaft.
As the concrete setting of above-mentioned scheme, the frame assembly is including the last roof that is used for installing dissolving tank body, active carbon decoloration section of thick bamboo and crystallization kettle, four corners of the lower surface of going up the roof all are connected with the stabilizer blade, four the lower extreme between the stabilizer blade still is provided with the bottom plate, first infusion pump and second infusion pump all set up on the bottom plate.
As the concrete setting of above-mentioned scheme, crude material loading machine and active carbon material loading machine all include a storage hopper, the lower extreme of storage hopper is connected with auger feeder, auger feeder's end connection has the unloading pipe.
The beneficial effects are that:
1) According to the posaconazole refining method disclosed by the invention, through the designed mixed liquid decoloring device, invalid activated carbon can be automatically discharged after each pair of mixed liquid with a set volume is decolored, and then new activated carbon particles are automatically subjected to adsorption decoloring under the action of the new activated carbon particles, so that the complete adsorption decoloring of all the mixed liquid can be effectively ensured, and the purity of the posaconazole obtained through the whole refining is effectively ensured.
2) The preparation device disclosed by the invention has a compact integral structure, the processes of dissolving the crude posaconazole product, adsorbing and decoloring the activated carbon and cooling and crystallizing the posaconazole product are realized, and the activated carbon in the decoloring process is quickly and conveniently replaced without being operated by operators, so that the refining efficiency of the posaconazole is greatly improved.
3) According to the crystal liquid separation device, the mixture is obliquely arranged in the feeding cylinder, when the crystal liquid mixture enters the feeding cylinder, the separation spiral blade has an obstruction effect on crystals so that the crystals cannot flow to the lower end of the feeding cylinder, liquid can be discharged from the liquid discharge pipe through the draining holes on the spiral under the action of self gravity, after the liquid is discharged completely, the separation spiral blade is started again so that the separation spiral blade rotates, and the crystals in the separation spiral blade are discharged from the transistor, so that the solid-liquid rapid separation after crystallization is realized, the structure design is novel, the solid-liquid rapid separation after crystallization can be effectively realized, and the use effect is excellent.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed for the description of the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a flow chart of steps of a method for preparing posaconazole according to the present invention;
FIG. 2 is a schematic view of a first angular perspective structure of the manufacturing apparatus according to the present invention;
FIG. 3 is a schematic view of a second perspective view of the apparatus according to the present invention;
FIG. 4 is a schematic view of the internal planar structure of a dissolution tank in the preparation apparatus of the present invention;
FIG. 5 is a schematic diagram of a three-dimensional structure of a tank cover, a crude product feeding machine, a stirring shaft and the like in the preparation device;
FIG. 6 is a schematic diagram of a three-dimensional structure of a filter screen frame, a filter screen, etc. in the preparation device of the invention;
FIG. 7 is a perspective semi-sectional view of a mixed liquor decoloring device in the manufacturing device of the present invention;
FIG. 8 is a schematic perspective view of a cartridge cover and a seal bearing in the manufacturing apparatus of the present invention;
FIG. 9 is an internal plan view of the mixed liquor decolorizer of the present invention in a liquid flow state;
FIG. 10 is a schematic view of a three-dimensional structure of a hollow rotating rod, a connecting disc, a spiral blade, etc. in the preparation device of the invention;
FIG. 11 is a schematic view showing the internal planar structure of a solution crystallization apparatus in the production apparatus of the present invention.
Wherein:
100-crude product dissolving device, 101-dissolving tank, 102-tank flange, 103-tank cover, 104-crude product feeder, 1041-storage hopper, 1042-auger feeder, 105-solvent injection pipe, 106-stirring motor, 107-stirring shaft, 108-stirring rod, 109-turning blade, 110-guide strip, 111-filter screen frame, 1111-limit port, 1112-round hole, 112-filter screen, 113-receiving plate, 114-first infusion tube, 115-first liquid valve, 116-first infusion pump, 117-heating heat preservation jacket;
200-mixed liquor decoloring device, 201-activated carbon decoloring cylinder, 202-cylinder cover, 203-sealing bearing, 204-hollow rotating rod, 205-connecting rod, 206-connecting disc, 207-rotating motor, 208-spiral blade, 209-waste discharge pipe, 210-sealing valve, 211-activated carbon feeder, 212-second infusion tube and 213-second infusion pump;
300-solution crystallization device, 301-crystallization kettle, 302-cooling medium jacket, 303-driving motor, 304-rotating shaft, 305-scraping plate, 306-crystal liquid separation device, 3061-feeding cylinder, 3062-separating motor, 3063-separating spiral blade, 3064-drain pipe, 3065-drain pipe, 3066-filter screen layer, 307-material valve;
400-frame assembly, 401-upper top plate, 402-support leg, 403-bottom plate, 500-control box.
Detailed Description
In order to make the present application solution better understood by those skilled in the art, the following description will be made in detail and with reference to the accompanying drawings in the embodiments of the present application, it is apparent that the described embodiments are only some embodiments of the present application, not all embodiments. All other embodiments, which can be made by one of ordinary skill in the art based on the embodiments herein without making any inventive effort, shall fall within the scope of the present application.
Furthermore, the terms "mounted," "configured," "provided," "connected," and "sleeved" are to be construed broadly. For example, it may be a fixed connection, a removable connection, or a unitary construction; may be a mechanical connection, or an electrical connection; may be directly connected, or indirectly connected through intervening media, or may be in internal communication between two devices, elements, or components. The specific meaning of the above terms in the present invention can be understood by those of ordinary skill in the art according to the specific circumstances.
It should be noted that, in the case of no conflict, the embodiments and features in the embodiments may be combined with each other. The present application will be described in detail with reference to fig. 1 to 11 in conjunction with examples.
Example 1
Example 1 discloses a process for the preparation of posaconazole, which comprises the following steps:
step one: injecting a solvent into a dissolving tank body, quantitatively putting the crude posaconazole product into the solvent through a crude product feeding machine, and rapidly dissolving the crude posaconazole product under the action of a stirring motor, wherein the solvent is ethyl acetate, the mass ratio of the crude posaconazole product to the crude posaconazole product is 1:8, and the temperature of the crude posaconazole product when dissolved is controlled to be 30 ℃.
Step two: the mixture obtained after dissolution is easily introduced into an activated carbon decoloring cylinder, the mixed solution enters the lower end of the activated carbon decoloring cylinder along a hollow rotating rod, flows upwards along a spiral blade, repeatedly contacts with activated carbon particles in the flowing process, adsorbs and decolors, and changes 0.8kg of activated carbon after decoloring every 26L of the mixed solution.
Step three: introducing the filtrate after adsorption and decolorization into a crystallization kettle for cooling, crystallizing at the temperature of minus 1 ℃, and separating the fully crystallized material into crystal liquid;
step four: washing the separated crystal with acetone, and vacuum drying to obtain refined posaconazole.
Example 2
Example 1 discloses a process for the preparation of posaconazole, which comprises the following steps:
step one: and injecting a solvent into the dissolution tank body, quantitatively putting the crude posaconazole product into the solvent through a crude product feeding machine, and rapidly dissolving the crude posaconazole product under the action of a stirring motor, wherein the solvent is acetone, the mass ratio of the crude posaconazole product to the crude posaconazole product is 1:6.8, and the temperature of the crude posaconazole product when dissolved is controlled to be 32 ℃.
Step two: the mixture obtained after dissolution is easily introduced into an activated carbon decoloring cylinder, the mixed solution enters the lower end of the activated carbon decoloring cylinder along a hollow rotating rod, flows upwards along a spiral blade, repeatedly contacts with activated carbon particles in the flowing process, adsorbs and decolors, and changes 1.1kg of activated carbon after decoloring every 22L of the mixed solution.
Step three: introducing the filtrate after adsorption and decolorization into a crystallization kettle for cooling, crystallizing at the temperature of 0 ℃, and separating the fully crystallized material into crystal liquid;
step four: washing the separated crystal with acetone, and vacuum drying to obtain refined posaconazole.
In summary, according to the posaconazole refining methods disclosed in embodiments 1 and 2, through designing the mixed solution decoloring device, each pair of mixed solutions with set volumes can be automatically discharged by invalid activated carbon after being decolored, and then new activated carbon particles are automatically adsorbed and decolored under the action of the new activated carbon particles, so that the complete adsorption and decoloration of all the mixed solutions can be effectively ensured, and the purity of the posaconazole obtained by the whole refining is effectively ensured.
Example 3
Embodiment 3 discloses a preparation device for use in steps 1-3 of embodiment 1 or embodiment 2, referring to fig. 2 and 3, comprising a frame assembly 400, wherein the frame assembly 400 comprises an upper top plate 401, legs 402 are connected to four corners of the lower surface of the upper top plate 401, and a bottom plate 403 is further arranged at the lower end between the four legs 402. The crude product dissolving device 100, the mixed solution decoloring device 200 and the solution crystallizing device 300 are sequentially arranged on an upper top plate 401 on the frame assembly 400, and a control box 500 is also arranged at the front end of the frame assembly 400.
Referring to fig. 4, 5 and 6, the crude product dissolving device 100 includes a dissolving tank 101, a tank flange 102 is connected to an upper end opening of the dissolving tank 101, a tank cover 103 is connected to the tank flange 102 through a fastening bolt, a crude product feeding machine 104 is disposed at one end of the tank cover 103, the crude product feeding machine 104 includes a storage hopper 1041, a packing auger feeder 1042 is connected to a lower end of the storage hopper 1041, a discharging pipe is connected to an end of the packing auger feeder 1042, and the discharging pipe penetrates through the tank cover 103, and can quantitatively discharge a crude posaconazole product in the storage hopper 1041 into the dissolving tank 101 under the action of the packing auger feeder 1042. Meanwhile, a solvent injection pipe 105 is arranged on the tank cover 103 positioned at the opposite side of the crude product feeding machine 104, and the solvent can be injected into the tank cover through the solvent injection pipe 105 to be mixed and dissolved with the crude posaconazole product.
In addition, in order to accelerate the dissolution rate of the posaconazole crude product, a stirring motor 106 is further arranged at the center of the upper surface of the tank cover 103, an output shaft of the stirring motor 106 is connected with a stirring shaft 107 extending into the dissolution tank 101, the upper end of the stirring shaft 107 is connected with a plurality of groups of stirring rods 108, and the lower end of the stirring shaft 107 is connected with a turning blade 109. The two ends all are connected with vertical gib block 110 about the inner wall of dissolving tank body 101, and the lower extreme of dissolving tank body 101 is provided with filter screen frame 111, and filter screen 112 has been laid to filter screen frame 111 upper surface, and filter screen frame 111's both ends have been seted up with gib block 110 assorted spacing mouth 1111, and filter screen frame 111's centre of a circle has been seted up and has been passed the round hole 1112 of (mixing) shaft, is provided with on the (mixing) shaft 107 that is located filter screen frame 111 below and holds the dish 113. The stirring device can accelerate the dissolution speed of the posaconazole crude product in the solvent, meanwhile, the filter screen 112 paved on the filter screen frame 111 can be used for fully filtering undissolved impurities, and then the posaconazole crude product can be taken out from the dissolution tank body 101 together with the tank body cover 103, the stirring mechanism and the filter screen frame 111 for cleaning. In order to ensure the solubility of the posaconazole crude product, a heating heat-preserving jacket 117 is further arranged on the outer side surface of the dissolution tank body 101, the upper end and the lower end of the heating heat-preserving jacket 117 are respectively connected with a heat medium inlet pipe and a heat medium outlet pipe, and the solvent can be heated by injecting heat conduction oil with a certain temperature into the heating heat-preserving jacket 117.
A first infusion tube 114 is connected to the lower end of the dissolution tank 101, a first liquid valve 115 is provided at the end of the first infusion tube 114 close to the dissolution tank 101, and a first infusion pump 116 is provided on the first infusion tube 114.
Referring to fig. 7, 8, 9 and 10, the mixed liquor decoloring device 200 includes an activated carbon decoloring cylinder 201, an upper end opening of the activated carbon decoloring cylinder 201 is connected with a cylinder cover 202 through a flange, and an end of the first transfer tube 114 is connected with a center of the cylinder cover 202. The inner wall at the centre of a circle of the cylinder cover 202 is provided with a sealing bearing 203, the sealing bearing 203 is rotationally connected with a hollow rotating rod 204, and the centre of a circle of an opening at the lower end of the hollow rotating rod 204 is connected with a connecting disc 206 through a plurality of connecting rods 205 which are circumferentially arranged. The lower extreme at active carbon decoloration section of thick bamboo 201 is provided with rotating electrical machines 207, rotating electrical machines 207's output shaft stretches into active carbon decoloration section of thick bamboo 201's inner chamber bottom and connection pad 206 are connected, hollow bull stick 204's outer disc is provided with helical blade 208 that is laminated mutually with active carbon decoloration section of thick bamboo 201 inner wall, active carbon decoloration section of thick bamboo 201's lower extreme still is provided with abandonment material calandria 209, be provided with sealing valve 210 on the abandonment material calandria 209, active carbon decoloration section of thick bamboo 201's upper end is connected with active carbon feeder 211, specifically active carbon feeder 211's specific structure is the same with crude material feeder 104, the liquid includes a storage hopper 1041 that is used for storing active carbon, storage hopper 1041's lower extreme is connected with auger feeder 1042, auger feeder 1042's end connection has the unloading pipe, this unloading pipe is linked together with active carbon decoloration section of thick bamboo 201's upper end. In addition, a second infusion tube 212 is further connected to the upper end of the activated carbon decolorizing canister 201, and a second infusion pump 213 is provided on the second infusion tube 212.
The mixed solution decoloring device 200 disclosed in this embodiment injects the mixed solution from the upper end of the hollow rotating rod 204, then discharges the mixed solution from the lower end to the periphery along the hollow rotating rod 204, and flows to the upper end of the activated carbon decoloring cylinder 201 along the direction of the spiral blade 208 after discharging, and fully contacts the activated carbon in the spiral blade 208 in the flowing process. Meanwhile, when the activated carbon is used for a while and loses the adsorption and decolorization effect, the injection of the mixed liquid into the waste discharge pipe 209 is stopped, then the sealing valve 210 on the waste discharge pipe 209 is opened, and simultaneously the rotating motor 207 is started to rotate the idle rotation lever 204, then the activated carbon in the activated carbon decolorization cylinder 201 is discharged along with the opening of the waste discharge pipe 209, and simultaneously the activated carbon feeder 211 refilled with new activated carbon.
Referring to fig. 11, the solution crystallization apparatus 300 includes a crystallization kettle 301, a cooling medium jacket 302 is provided on an outer surface of the crystallization kettle 301, and inlet pipes and outlet pipes are provided at upper and lower ends of the cooling medium jacket 302, respectively, through which a low-temperature cooling medium (such as ice water, or a small amount of liquid nitrogen) can be injected into the cooling medium jacket 302. A driving motor 303 is arranged at the top end of the crystallization kettle 301, a rotating shaft 304 is connected to the lower end of the output shaft of the driving motor 303 extending into the crystallization kettle 301, a scraping plate 305 attached to the inner wall of the crystallization kettle 301 is connected to the lower end of the rotating shaft 304, and a plurality of groups of stirring rods are also arranged at the upper end of the rotating shaft 304 in order to accelerate uniform cooling of filtrate during crystallization. A discharging pipe is connected to the lower end of the crystallization kettle 301, a material valve 307 is arranged on the discharging pipe, and a crystal liquid separation device 306 is connected to the lower end of the discharging pipe.
Specifically, the crystal liquid separation device 306 comprises a feeding barrel 3061 which is obliquely arranged, the middle section of the feeding barrel 3061 is connected with the lower end of a discharging pipe, a separation motor 3062 is arranged on the end face of the feeding barrel 3061, a separation spiral blade 3063 is connected to the end portion of an output shaft of the separation motor 3062 extending into the feeding barrel 3061, a large number of draining holes are formed in the surface of the separation spiral blade 3063, the lower inclined end of the feeding barrel 3061 is connected with a discharging pipe 3064, and the upper inclined end of the feeding barrel 3061 is connected with a transistor 3065. Further, a filter screen layer 3066 is further provided at the upper end of the drain 3064. Above-mentioned brilliant liquid separator 306 sets up pay-off feed cylinder 3061 slope, and in the feed cylinder 3061 was got into to the brilliant liquid mixture after opening material valve 307, separation spiral leaf 3063 had the effect of blocking to the crystal and makes it unable to roll to the lower extreme of feed cylinder 3061, and liquid then can be discharged from the fluid-discharge tube 3064 under self gravity effect, after the liquid is discharged, the restart separation spiral leaf 3063 makes separation spiral leaf 3063 rotatory to with inside crystal from discharging transistor 3065.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the invention.
Claims (4)
1. The preparation device is equipment in the following steps 1) -3), and comprises a frame assembly (400), and is characterized in that a crude product dissolving device (100), a mixed liquid decoloring device (200) and a solution crystallization device (300) are sequentially arranged at the upper end of the frame assembly (400), and a control box (500) is further arranged at the front end of the frame assembly (400);
wherein, crude dissolving device (100) is including dissolving jar body (101), the upper end opening of dissolving jar body (101) is connected with jar body flange (102), be connected with jar body lid (103) through fastening bolt on jar body flange (102), the one end of jar body lid (103) is provided with crude material loading machine (104), is located be provided with solvent injection pipe (105) on jar body lid (103) of crude material loading machine (104) contralateral side, the upper surface centre of a circle department of jar body lid (103) is provided with agitator motor (106), be connected with (107) in stretching into dissolving jar body (101) on the output shaft of agitator motor (106), the upper end of (107) is connected with multiunit stirring rod (108), the lower extreme of (107) is connected with turns over material leaf (109), the inner wall left and right sides of dissolving jar body (101) all is connected with vertical guide strip (110), the lower extreme of dissolving jar body (101) is provided with filter screen frame (111), the upper surface (111) is equipped with filter screen frame (1111), filter screen frame (111) and filter screen frame (111) are opened in the centre of a circle (1111) are stretched into in advance, a bearing disc (113) is arranged on a stirring shaft (107) below the filter screen frame (111), the lower end of the dissolution tank body (101) is connected with a first infusion tube (114), a first liquid valve (115) is arranged at the end part of the first infusion tube (114) close to the dissolution tank body (101), and a first infusion pump (116) is arranged on the first infusion tube (114);
the mixed liquid decoloring device (200) comprises an activated carbon decoloring cylinder (201), an upper end opening of the activated carbon decoloring cylinder (201) is connected with a cylinder cover (202) through a flange, the end part of a first infusion tube (114) is connected with the circle center of the cylinder cover (202), a sealing bearing (203) is arranged on the inner wall of the circle center of the cylinder cover (202), a hollow rotating rod (204) is rotationally connected with the sealing bearing (203), a plurality of connecting rods (205) arranged at the circle center of the lower end opening of the hollow rotating rod (204) in the circumferential direction are connected with a connecting disc (206), the lower end of the activated carbon decoloring cylinder (201) is provided with a rotary motor (207), an output shaft of the rotary motor (207) extends into the bottom of an inner cavity of the activated carbon decoloring cylinder (201) to be connected with the connecting disc (206), spiral blades (208) attached to the inner wall of the activated carbon decoloring cylinder (201) are arranged on the outer circle surface of the hollow rotating rod (204), a waste carbon discharging tube (209) is further arranged at the lower end of the activated carbon decoloring cylinder (201), a waste carbon discharging tube (210) is further connected with an activated carbon discharging tube (212) at the upper end of the activated carbon decoloring cylinder (201), a second infusion pump (213) is arranged on the second infusion tube (212);
the solution crystallization device (300) comprises a crystallization kettle (301), a cooling medium jacket (302) is arranged on the outer surface of the crystallization kettle (301), an inlet pipe and a discharge pipe are respectively arranged at the upper end and the lower end of the cooling medium jacket (302), a driving motor (303) is arranged at the top end of the crystallization kettle (301), an output shaft of the driving motor (303) stretches into the middle lower end of the crystallization kettle (301) and is connected with a rotating shaft (304), a scraping plate (305) attached to the inner wall of the crystallization kettle (301) is connected with the lower end of the rotating shaft (304), a discharge pipe is connected with the lower end of the crystallization kettle (301), a material valve (307) is arranged on the discharge pipe, and the lower end of the discharge pipe is connected with a crystal-liquid separation device (306);
the crystal liquid separation device (306) comprises a feeding barrel (3061) which is obliquely arranged, the middle section of the feeding barrel (3061) is connected with the lower end of a discharging pipe, a separation motor (3062) is arranged on the end face of the feeding barrel (3061), a separation spiral blade (3063) is connected with the end part of an output shaft of the separation motor (3062) extending into the feeding barrel (3061), a large number of draining holes are formed in the surface of the separation spiral blade (3063), a drain pipe (3064) is connected with the lower inclined end of the feeding barrel (3061), and a transistor (3065) is connected with the upper inclined end of the feeding barrel (3061);
the upper end of the liquid discharge pipe (3064) is also provided with a filter screen layer (3066);
the crude product feeding machine (104) and the activated carbon feeding machine (211) comprise a storage hopper (1041), the lower end of the storage hopper (1041) is connected with an auger feeding machine (1042), and the end part of the auger feeding machine (1042) is connected with a discharging pipe;
when the preparation device is used for preparing posaconazole, the preparation device comprises the following steps:
1) Injecting a solvent into the dissolution tank body, quantitatively putting the crude posaconazole product into the solvent through a crude product feeding machine, and rapidly dissolving the crude posaconazole product under the action of a stirring motor;
2) Introducing the dissolved mixed solution into an activated carbon decoloring cylinder, allowing the mixed solution to enter the lower end of the activated carbon decoloring cylinder along a hollow rotating rod, then allowing the mixed solution to flow upwards along a spiral blade, repeatedly contacting with activated carbon particles in the flowing process, adsorbing and decoloring, and replacing 0.6-1.4kg of activated carbon after decoloring every 20-30L of mixed solution;
3) Introducing the filtrate after adsorption and decolorization into a crystallization kettle for cooling, crystallizing at the temperature of-2-4 ℃, and separating the fully crystallized material into crystal liquid;
4) Washing the separated crystal, and vacuum drying after washing to obtain refined posaconazole;
the solvent is one or more of ethyl acetate and acetone;
the temperature of the crude posaconazole product when dissolved is 26-32 ℃.
2. The preparation device according to claim 1, wherein the outer side surface of the dissolution tank body (101) is further provided with a heating and heat-preserving jacket (117), and the upper end and the lower end of the heating and heat-preserving jacket (117) are respectively connected with a heat medium inlet pipe and a heat medium outlet pipe.
3. The preparation device according to claim 1, characterized in that the upper end of the rotating shaft (304) is also provided with a plurality of sets of stirring bars.
4. The preparation device according to claim 1, wherein the rack assembly (400) comprises an upper top plate (401) for installing the dissolution tank body (101), the activated carbon decolorizing drum (201) and the crystallization kettle (301), four corners of the lower surface of the upper top plate (401) are respectively connected with a support leg (402), a bottom plate (403) is further arranged at the lower end between the four support legs (402), and the first infusion pump (116) and the second infusion pump (213) are respectively arranged on the bottom plate (403).
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106147831A (en) * | 2016-09-21 | 2016-11-23 | 重庆方盛净化设备有限公司 | Waste oil fast purification decolouring integrated device |
| CN107019953A (en) * | 2017-05-27 | 2017-08-08 | 湖北华丹医药科技股份有限公司 | A kind of positive pressure-off charcoal conveying device of bulk drug crystallizing tank liquid material |
| CN110204626A (en) * | 2019-06-17 | 2019-09-06 | 日照职业技术学院 | A kind of device and method sea cucumber polysaccharide separation and refined |
| CN211284202U (en) * | 2019-11-28 | 2020-08-18 | 威海厚普生物科技有限公司 | New salt forming system for high-purity loxoprofen sodium |
| CN112824400A (en) * | 2019-11-20 | 2021-05-21 | 华创合成制药股份有限公司 | Preparation method of posaconazole |
| CN112898279A (en) * | 2019-11-19 | 2021-06-04 | 爱之源生物科技有限公司 | Refining method of high-purity posaconazole |
-
2021
- 2021-12-30 CN CN202111651018.4A patent/CN114195770B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106147831A (en) * | 2016-09-21 | 2016-11-23 | 重庆方盛净化设备有限公司 | Waste oil fast purification decolouring integrated device |
| CN107019953A (en) * | 2017-05-27 | 2017-08-08 | 湖北华丹医药科技股份有限公司 | A kind of positive pressure-off charcoal conveying device of bulk drug crystallizing tank liquid material |
| CN110204626A (en) * | 2019-06-17 | 2019-09-06 | 日照职业技术学院 | A kind of device and method sea cucumber polysaccharide separation and refined |
| CN112898279A (en) * | 2019-11-19 | 2021-06-04 | 爱之源生物科技有限公司 | Refining method of high-purity posaconazole |
| CN112824400A (en) * | 2019-11-20 | 2021-05-21 | 华创合成制药股份有限公司 | Preparation method of posaconazole |
| CN211284202U (en) * | 2019-11-28 | 2020-08-18 | 威海厚普生物科技有限公司 | New salt forming system for high-purity loxoprofen sodium |
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