CN213493623U

CN213493623U - Transfer reactor and system for dipalmitoyl phosphatidylcholine preparation process

Info

Publication number: CN213493623U
Application number: CN202020969107.8U
Authority: CN
Inventors: 杨山水; 李颖; 杨锋; 程彦丰; 杨静
Original assignee: Nanjing Jinkaimu Nano Materials Co ltd
Current assignee: Nanjing Jinkaimu Nano Materials Co ltd
Priority date: 2020-06-01
Filing date: 2020-06-01
Publication date: 2021-06-22
Anticipated expiration: 2030-06-01

Abstract

The utility model provides a transfer reactor and a system for preparing dipalmitoyl phosphatidylcholine, which comprises a bottle body; the bottle body is provided with a water bath interlayer; the top of the bottle body is provided with a main feed port, the upper part of the bottle body is provided with one or a plurality of secondary feed ports, and the middle part of the bottle body is provided with a suction filter port; the lower part of the water bath interlayer is provided with a water inlet; the upper part is provided with a water outlet; the lower part of the bottle body is provided with a discharge hole; the feed inlet and the discharge outlet are both in a circular truncated cone shape, and the diameter of the upper circle is larger than that of the lower part; and a neck pipe with a reduced caliber is arranged at the lower part of the inner wall of the main feed port. The utility model discloses can realize a plurality of reactors series operation, and can support nimble combination, only need connect the reactor in advance, or with the whole split of reactor unit, the recombination just can realize the material and transport, need not take out the material and transport, effectively avoids harmful solvent such as chloroform, acetone to volatilize, pollutes operating environment, also reduces the loss that causes when taking out middle material.

Description

Transfer reactor and system for dipalmitoyl phosphatidylcholine preparation process

Technical Field

The utility model belongs to the field of pharmaceutical chemicals, in particular to transfer reactor and system application that preparation dipalmitoyl phosphatidylcholine technology was used.

Background

Phospholipid is an important component of a biological membrane, a polar end containing phosphate radical has hydrophilicity, and two longer non-polar ends of hydrocarbon chains have lipophilicity, and the unique physicochemical property enables the phospholipid to form a closed bilayer in an aqueous medium spontaneously to form a biological membrane skeleton, so that the phospholipid plays an important role in the liposome technology.

However, natural phospholipids have disadvantages of short lifetime, easy oxidation, and poor stability as liposome materials, and thus have limited applications. Dipalmitoyl phosphatidylcholine (DPPC) is an important artificially synthesized phospholipid, is mainly applied to the preparation of liposome, is an indispensable additive auxiliary material in liposome pharmaceutical preparations, has high purity and good stability, has stronger oxidation resistance than natural phospholipid, has ideal liposome preparation effect, wide application prospect and large demand.

Dipalmitoyl phosphatidylcholine is prepared by a mature process, but the existing process uses a laboratory standard vessel, and the reaction vessel has single function and small preparation amount and is not suitable for industrial application; meanwhile, the dipalmitoyl phosphatidylcholine preparation route mostly involves the repeated use of organic solvents such as chloroform, acetone, butanone and dichloromethane for dissolution and suction filtration; wherein the material is transported many times not only complex operation, and the volatilization of organic solvent can also cause the influence to operating personnel's health safety. Therefore, the development of a transfer reactor which is suitable for industrial production, simple and safe to use is necessary for the large-scale industrial production of dipalmitoyl phosphatidylcholine.

SUMMERY OF THE UTILITY MODEL

In order to solve the problems, the utility model provides a transfer reactor for preparing dipalmitoyl phosphatidylcholine process.

In order to achieve the above purpose, the utility model adopts the following technical scheme:

a transfer reactor for preparing dipalmitoyl phosphatidylcholine process comprises a bottle body; the bottle body is provided with a water bath interlayer; the top of the bottle body is provided with a main feed port, the upper part of the bottle body is provided with one or a plurality of secondary feed ports, and the middle part of the bottle body is provided with a suction filter port; the lower part of the water bath interlayer is provided with a water inlet; the upper part is provided with a water outlet; the lower part of the bottle body is provided with a discharge hole; the feed inlet and the discharge outlet are both in a circular truncated cone shape, and the diameter of the upper circle is larger than that of the lower part; and a neck pipe with a reduced caliber is arranged at the lower part of the inner wall of the main feed port.

The reactor also comprises a filter funnel which adopts a Buchner funnel and is detachably arranged in the neck pipe.

A discharge pipe with an electromagnetic valve is arranged in the discharge hole.

Furthermore, the main feed inlet is provided with an upper coupler, and the discharge outlet is provided with a lower coupler; the upper part of the upper coupling is connected with an upper connecting shaft; the lower part of the lower coupling is provided with a lower coupling shaft; the bottom of the lower connecting shaft is a non-circular column, and the top of the upper connecting shaft is provided with a vertical hole in clearance fit with the non-circular column at the bottom of the lower connecting shaft; a stirring shaft is vertically arranged between the upper coupler and the lower coupler, and a foldable stirring blade is arranged on the stirring shaft.

Furthermore, a through hole which is in running fit with the upper connecting shaft is arranged in the center of the filter hopper; and a sealing gasket is arranged in the through hole.

Further, the reactor also comprises a cover body, the cover body is provided with a grid for installing the absorption unit and a motor, and an output shaft of the motor is in transmission connection with the upper connecting shaft.

Preferably, the inner wall of the main feed inlet and the outer wall of the discharge outlet of the reactor are frosted surfaces.

Further, the utility model provides a reaction system with multiple reactors connected in series, which comprises a vertical stack of reactor units formed by more than one transfer reactor, wherein the discharge port of the upper reactor unit is inserted into the main feed port of the lower reactor unit; the lower connecting shaft of the upper reactor is in clearance fit connection with the upper connecting shaft of the lower reactor.

Through the technical scheme, the utility model realizes the series operation of a plurality of reactors, can support flexible combination, can realize material transportation by only connecting the reactors in advance or splitting and recombining the whole reactor unit, does not need to take out the materials for transportation, effectively avoids the volatilization of harmful solvents such as chloroform, acetone and the like, pollutes the operation environment, and also reduces the loss caused by taking out the intermediate materials; when the filter cake needs to be repeatedly filtered, only the filter hopper with the filter cake needs to be transported independently.

The utility model has the advantages of simple and reasonable structure, strong adaptability and safe operation, and effectively meets the industrial production requirement of the dipalmitoyl phosphatidylcholine preparation process or the similar process.

Drawings

FIG. 1 is a schematic view of the structure of a transfer reactor bottle of the present invention;

FIG. 2 is a top view of the filter funnel of the present invention;

fig. 3 is a schematic structural diagram of the cover body of the present invention.

Wherein, 1, a bottle body; 2. water bath interlayer; 3. a main feed inlet; 4. a discharge port; 5. a secondary feed port; 6. a filtration port is pumped; 7. a water inlet; 8. a water outlet; 9. a neck tube; 10. a discharge pipe; 11. an electromagnetic valve; 12. a stirring shaft; 13. an upper coupling; 14. an upper coupling shaft; 15. a lower coupling; 16. a lower coupling shaft; 17. a through hole; 18. a sealing gasket; 19. A motor; 20. an output shaft; 21. and (4) grid.

Detailed Description

The technical solution of the present invention is further described below by referring to the drawings and specific embodiments, and the following embodiments are only used to more clearly illustrate the technical solution of the present invention, and the protection scope of the present invention is not limited thereby.

The embodiment is a reaction system with multiple reactors connected in series, which comprises two reactor units stacked vertically, wherein a discharge port 4 of an upper reactor unit is inserted into a main feed port 3 of a lower reactor unit; the lower coupling shaft 16 of the upper reactor and the upper coupling shaft 14 of the lower reactor are coupled with clearance fit.

A transfer reactor constituting each reactor unit, including a bottle body 1; the bottle body 1 is provided with a water bath interlayer 2; the top of the bottle body is provided with a main feed port 3, the upper part of the bottle body is provided with one or a plurality of secondary feed ports 5, and the middle part of the bottle body 1 is provided with a suction filtration port 6; the lower part of the water bath interlayer 2 is provided with a water inlet 7; the upper part is provided with a water outlet 8; the lower part of the bottle body is provided with a discharge hole 4; the main feed port 3 and the discharge port 4 are both in a circular truncated cone shape, and the diameter of an upper circle is larger than that of a lower circle; the lower part of the inner wall of the main feed port 3 is provided with a neck pipe 9 with a reduced caliber.

The reactor also comprises a filter funnel which adopts a Buchner funnel and is detachably arranged in the neck pipe 9.

A discharge pipe 10 with an electromagnetic valve 11 is arranged in the discharge port 4.

The main feed port 3 is provided with an upper coupler 13, the discharge port 4 is provided with a lower coupler 15, and the upper part of the upper coupler 13 is connected with an upper connecting shaft 14; the lower part of the lower coupling 15 is provided with a lower coupling shaft 16; the bottom of the lower connecting shaft is a non-circular column, and the top of the upper connecting shaft is provided with a vertical hole in clearance fit with the non-circular column at the bottom of the lower connecting shaft; a stirring shaft 12 is vertically arranged between the upper coupler 13 and the lower coupler 15, and a foldable stirring blade is arranged on the stirring shaft 12.

The center of the filter hopper is provided with a through hole 17 which is rotationally matched with the upper connecting shaft; a sealing washer 18 is arranged in the through hole.

The reactor also comprises a cover body, the cover body is provided with a grid 21 for installing the absorption units and a motor 19, and an output shaft 20 of the motor is in transmission connection with the upper connecting shaft 14.

The inner wall of the main feed inlet 3 and the outer wall of the discharge outlet 4 of the reactor are frosted surfaces.

In one application scheme of the embodiment, the upper reactor closes the electromagnetic valve 11, the secondary feed port 5 and the suction filtration port 6, and opens the water bath interlayer 2 for water bath circulation; adding glycerophosphorylcholine; palmitic acid; DMAP; trichloromethane and other reactants, covering the cover body, connecting the connecting shaft 14, starting the motor 19, magnetically stirring uniformly, opening one secondary feeding hole 5, and introducing argon for replacement protection; and opening a second secondary feeding hole 5, and quickly dropwise adding the DCC chloroform solution into the reaction system to generate insoluble solids after the reaction is finished.

Placing a filter hopper and filter paper in the lower reactor, closing the electromagnetic valve 11 and the secondary feed port valve 5, preparing air suction at a suction filtration port, connecting the water bath interlayer 2 with the water bath, and connecting one secondary feed port 5 with a condenser pipe;

after the reaction of the upper reactor is finished, opening the suction device at the suction filtration port 6 of the lower reactor, opening the electromagnetic valve 11 of the upper reactor, and starting suction filtration for the first time to remove insoluble solids; opening a valve of a secondary feed port 5 connected with a condensing pipe, heating the liquid phase by a water bath of a reactor at the lower part, and evaporating to obtain yellow viscous liquid; opening a valve of a secondary feed port 5 of the lower reactor, injecting acetone, starting a motor for pulping, and separating out a large amount of white solids in the system;

replacing the upper reactor and the lower reactor, and repeating the suction filtration process; after suction filtration, replacing the filter hopper, adding the white solid in the replaced lower filter hopper into the replaced upper reactor, adding dichloromethane into the secondary feed inlet of the upper reactor, starting a motor for stirring, controlling the temperature through water bath, and performing suction filtration again after the reaction is finished; the filtrate after suction filtration is put into a lower reactor after replacement, MTBE is dripped into the lower reactor through a secondary feed inlet 5, and the mixture is stirred until a large amount of solids are separated out;

and replacing the position of the reactor again, and performing suction filtration to obtain a qualified DPPC product.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, a plurality of modifications and variations can be made without departing from the technical principle of the present invention, and these modifications and variations should also be considered as the protection scope of the present invention.

Claims

1. A transfer reactor for preparing dipalmitoyl phosphatidylcholine process comprises a bottle body; the bottle body is provided with a water bath interlayer; the top of the bottle body is provided with a main feed port, the upper part of the bottle body is provided with one or a plurality of secondary feed ports, and the middle part of the bottle body is provided with a suction filter port; the lower part of the water bath interlayer is provided with a water inlet; the upper part is provided with a water outlet; the lower part of the bottle body is provided with a discharge hole;

the method is characterized in that: the feed inlet and the discharge outlet are both in a circular truncated cone shape, and the diameter of the upper circle is larger than that of the lower part; a neck pipe with a reduced caliber is arranged at the lower part of the inner wall of the main feed port; the reactor also comprises a filter funnel which adopts a Buchner funnel and is detachably arranged in the neck pipe; a discharge pipe with an electromagnetic valve is arranged in the discharge hole.

2. The transfer reactor for the process of preparing dipalmitoyl phosphatidylcholine according to claim 1, wherein the main feed inlet is provided with an upper coupling, and the discharge outlet is provided with a lower coupling; the upper part of the upper coupling is connected with an upper connecting shaft; the lower part of the lower coupling is provided with a lower coupling shaft; the bottom of the lower connecting shaft is a non-circular column, and the top of the upper connecting shaft is provided with a vertical hole in clearance fit with the non-circular column at the bottom of the lower connecting shaft; a stirring shaft is vertically arranged between the upper coupler and the lower coupler, and a foldable stirring blade is arranged on the stirring shaft.

3. The transfer reactor for dipalmitoyl phosphatidylcholine preparation process according to claim 2, wherein the filter funnel is provided with a through hole in the center, which is rotatably matched with the upper connecting shaft; and a sealing gasket is arranged in the through hole.

4. The transfer reactor for the process of preparing dipalmitoyl phosphatidylcholine according to claim 2 or 3, wherein said reactor further comprises a cover body, said cover body is provided with a grid for installing absorption unit, and is installed with a motor, the output shaft of said motor is connected with the upper connecting shaft in a transmission way.

5. The transfer reactor for dipalmitoyl phosphatidylcholine preparation process according to one of claims 1-3, wherein said reactor main inlet inner wall and outlet outer wall are frosted surface.

6. A multi-reactor series reaction system comprising one or more reactor units consisting of transfer reactors according to any one of claims 1 to 3, wherein the reactor units are vertically stacked, and the discharge port of the upper reactor unit is inserted into the main feed port of the lower reactor unit; the lower connecting shaft of the upper reactor is in clearance fit connection with the upper connecting shaft of the lower reactor.