CN212524043U

CN212524043U - Polypeptide medicine microsphere preparation system based on submerged airflow spraying

Info

Publication number: CN212524043U
Application number: CN202020875325.5U
Authority: CN
Inventors: 于崆峒; 蒋朝军; 刘喜明
Original assignee: Zhejiang Sundoc Pharmaceutical Science And Tech Co ltd
Current assignee: Zhejiang Sundoc Pharmaceutical Science And Tech Co ltd
Priority date: 2020-05-22
Filing date: 2020-05-22
Publication date: 2021-02-12
Anticipated expiration: 2030-05-22

Abstract

The utility model discloses a polypeptide medicine microballon preparation system based on air current spraying under liquid, including interior water phase jar (1), oil phase jar (2), colostrum shearing tank (3), drier in the liquid (4) and compressed air storage tank (5), interior water phase jar (1) and oil phase jar (2) are connected to colostrum shearing tank through interior water phase injection passageway (6) and oil phase injection passageway (7) respectively, drier in the liquid (4) bottom is equipped with air jet nozzle (8), the discharge gate of colostrum shearing tank (3) and the gas outlet of compressed air storage tank (5) are connected with air jet nozzle (8) through the pipeline respectively. The utility model discloses balling-up rate is high, and productivity is high, and microballon blastocyst is timely with outer water phase contact, can not produce the gathering, can not form a large amount of films.

Description

Polypeptide medicine microsphere preparation system based on submerged airflow spraying

Technical Field

The utility model relates to a medicine microballon production technical field, in particular to polypeptide medicine microballon preparation system based on submerged air current spraying.

Background

Microspheres refer to a dispersion of microparticles in which a drug is dispersed or adsorbed in a polymeric or polymeric matrix. Compared with the traditional preparation, the microsphere can reduce the administration times, improve the compliance of patients, reduce the side effect and improve the curative effect, has obvious advantages in clinic and becomes a hot spot for the research and development of new medicament forms in recent years. The microsphere preparation technology capable of realizing industrialization firstly can ensure the controllability of key quality attributes (CQAs), such as: the form, the grain diameter and the grain diameter distribution of the microspheres, the drug-loading rate, the encapsulation rate, the in vitro release degree and other CQAs are well controlled, and the microsphere has great promotion effect on the development and the technical transformation of the drug. Especially for polypeptide protein drugs, the raw material drugs are expensive, and the production scale (batch) determines the production cost of a single preparation.

For hydrophilic drugs, there are 3 typical formulation methods: multiple emulsion method, phase separation method and spray drying method. The 3 methods all have similar initial process steps, namely adding an aqueous phase solution of the medicament into an oil phase solution formed by an organic solvent and a polymer, emulsifying to form water-in-oil (W1/O) colostrum, and then respectively adopting differential medium and dispersion modes to prepare the microspheres.

Compared with a multiple emulsion method and a phase separation method, the spray drying method is most easy to realize batch amplification, is not limited by the flux (treatment capacity) of shearing equipment, and can realize continuous spray granulation. The traditional spray drying method is that the feed liquid (which can be emulsion, true solution or suspension) is sprayed into the dry inert gas flow with gradually increased temperature, the organic solvent is quickly evaporated, and the organic solvent is solidified into balls. The spray drying method does not need to use a large amount of organic reagents, is slightly influenced by the properties of high polymers, and has higher microsphere encapsulation efficiency and good batch-to-batch reproducibility. However, when the polypeptide protein microspheres are prepared by the method, polypeptide protein drugs are extremely easy to inactivate by high-temperature airflow, so that no microsphere product which is marketed by the method exists at present.

Chinese patent CN1879606B discloses a delivery system for preparing novel drugs based on a liquid surface spraying method, which proposes a method for preparing microspheres by air-flow spraying from the liquid surface to the external aqueous phase, specifically, the method comprises mixing or suspending a solution containing a carrier material with a drug or a drug solution, atomizing the mixture by controlling the air pressure, and spraying the atomized mixture into a receiving liquid to form a microparticle preparation. However, in the course of research, the inventors of the present application found that the preparation of microspheres in this way is not easy to achieve, and the biggest problem is that when a primary emulsion (greater than 1000 cp) with high viscosity is sprayed onto the surface of an aqueous solution (such as PVA), a large amount of thin film is inevitably formed even under stirring, the polymer solution at the gas-liquid interface is not timely and fully surrounded by water, the surface of the microspheres is not solidified, and aggregation (similar to the dissolution phenomenon of sodium carboxymethylcellulose) is very easy to occur, resulting in a very low sphere forming rate of the microspheres.

Disclosure of Invention

The utility model aims at providing a polypeptide medicine microballon preparation system based on air current spraying under liquid, balling-up rate is high, and productivity is high, and microballon blastocyst is timely with outer water phase contact, can not produce the gathering, can not form a large amount of films.

The utility model provides a technical scheme that its technical problem adopted is:

the utility model provides a polypeptide medicine microballon preparation system based on air current spraying under liquid, including interior water phase jar (1), oil phase jar (2), colostrum shearing tank (3), drier in the liquid (4) and compressed air storage tank (5), interior water phase jar (1) and oil phase jar (2) are connected to colostrum shearing tank through interior water phase injection passageway (6) and oil phase injection passageway (7) respectively, drier in the liquid (4) bottom is equipped with air current nozzle (8), the discharge gate of colostrum shearing tank (3) and the gas outlet of compressed air storage tank (5) are connected with air current nozzle (8) through the pipeline respectively.

Different from the method that prior art from the liquid level outside aqueous phase spraying formed the microballon, the utility model discloses a new method, from the submerged of outer aqueous phase from lower supreme spout outer aqueous phase with the primary emulsion, balling-up rate is high, and the productivity is high, and microballon blastocyst is timely with outer aqueous phase contact, can not produce the gathering, can not form a large amount of films. Thereby solving the technical problems that a large amount of polymer films are formed when high-concentration and high-viscosity feed liquid is sprayed into the liquid surface from top to bottom, the spheres cannot be divided, and the yield is low.

The principle of the utility model is that: the prepared primary emulsion is fed into an air flow nozzle at a certain flow rate, the solution is dispersed into uniform micro-droplets by controlling the viscosity of the primary emulsion and the air flow rate of the air flow nozzle through the crushing action of air flowing through the nozzle opening, the micro-droplets are uniformly dispersed into an external water phase under the stirring condition when being formed, the micro-droplets are not directly contacted with the external air, the organic solvent of the formed double emulsion is removed under the stirring condition, and finally the double emulsion is solidified to form the microspheres.

Preferably, the gas flow nozzle (8) consists of a liquid inlet (81), a gas inlet (82) and a top nozzle (83), the discharge port of the colostrum shearing tank (3) is connected with the liquid inlet (81) through a pipeline, and the air outlet of the compressed air storage tank (5) is connected with the gas inlet (82) through a pipeline.

Preferably, a water-based filter membrane for filtering the internal water phase is arranged in the internal water phase injection channel (6).

Preferably, an oil-based filter membrane for filtering the oil phase is provided in the oil phase injection passage (7).

Preferably, an oil phase pump (11) is provided in the oil phase injection passage (7).

Preferably, the gas flow nozzle (8) is hermetically connected with the drying tank (4) in liquid through a nozzle tank bottom sealing piece (9).

Preferably, a colostrum shearing machine (31) is arranged on the colostrum shearing tank (3).

Preferably, a temperature control jacket (41) is arranged on the outer side of the liquid medium drying tank (4), an exhaust port (42) is arranged at the top of the liquid medium drying tank (4), and a gas filter membrane (43) is arranged on the exhaust port (42).

Preferably, a stirrer (44) is arranged on the submerged drying tank (4), the stirrer (44) is connected with the submerged drying tank (4) in a sealing mode, and a stirring paddle (441) of the stirrer (44) is located 5-10cm above the airflow nozzle.

Preferably, the air outlet of the compressed air storage tank (5) is also connected with the oil phase injection channel (7) through a pipeline.

The utility model has the advantages that: high balling rate and yield, timely contact between the microsphere blastocyst and external water, no aggregation and no formation of great amount of film.

Drawings

Fig. 1 is a schematic structural diagram of the present invention.

Detailed Description

The technical solution of the present invention is further specifically described below by way of specific examples.

In the utility model, if not, the adopted raw materials and equipment can be purchased from the market or commonly used in the field. The methods in the following examples are conventional in the art unless otherwise specified.

Example 1:

as shown in fig. 1, the system for preparing polypeptide drug microspheres based on submerged airflow spraying comprises an inner water phase tank 1, an oil phase tank 2, a colostrum shearing tank 3, a submerged drying tank 4 and a compressed air storage tank 5, wherein the inner water phase tank 1 and the oil phase tank 2 are respectively connected to the colostrum shearing tank 7 through an inner water phase injection channel 6 and an oil phase injection channel 7, a water system filter membrane for filtering the inner water phase is arranged in the inner water phase injection channel 6, an oil system filter membrane for filtering the oil phase is arranged in the oil phase injection channel 7, and an oil phase pump 11 is further arranged on the oil phase injection channel 7. And an air flow nozzle 8 is arranged at the bottom of the drying tank 4 in the liquid, and the air flow nozzle 8 is hermetically connected with the drying tank 4 in the liquid through a nozzle tank bottom sealing element 9.

The air flow nozzle 8 consists of a liquid inlet 81, an air inlet 82 and a top nozzle 83, a discharge hole of the primary emulsion shearing tank 3 is connected with the liquid inlet 81 through a pipeline, one end opening of a discharge pipeline 32 which is connected with the primary emulsion shearing tank and the liquid inlet 81 extends into the center of the bottom of the primary emulsion shearing tank, and an air outlet of the compressed air storage tank 5 is connected with the air inlet 82 through a pipeline; the air outlet of the compressed air storage tank 5 is also connected with the oil phase injection channel 7 through a pipeline. A pipeline of the compressed air storage tank 5 connected with the gas inlet 82 is provided with a gas flowmeter 10 with an adjusting valve, and a pipeline of the compressed air storage tank 5 connected with the oil phase injection channel 7 is also provided with the gas flowmeter 10 with an adjusting valve. The colostrum shearing tank 3 is provided with a colostrum shearing machine 31. Specifically, a commercially available Japanese-compatible two-fluid nozzle can be selected as the air flow nozzle of this embodiment.

The outside of the drying tank 4 in the liquid is provided with a temperature control jacket 41, the top of the drying tank 4 in the liquid is provided with an exhaust port 42, and the exhaust port 42 is provided with a gas filter membrane 43. The liquid drying tank 4 is provided with a stirrer 44, the stirrer 44 is hermetically connected with the liquid drying tank 4, and a stirring paddle 441 of the stirrer 44 extends into the liquid drying tank and is positioned 5-10cm above the top nozzle 83 of the air flow nozzle. The stirring paddle 441 is positioned 5-10cm above the top nozzle 83 of the air flow nozzle to enhance the stirring dispersion effect.

The utility model discloses a work flow does:

(1) dissolving a polypeptide drug in an aqueous solution to form an internal water phase, placing the internal water phase in an internal water phase tank 1, dissolving a polymer in an organic solvent to form an oil phase, placing the oil phase in an oil phase tank 2, filtering the internal water phase in the internal water phase tank 1 and the oil phase in the oil phase tank 2 through an internal water phase injection channel 6 and an oil phase injection channel 7 respectively, injecting the filtered internal water phase and the filtered oil phase into a colostrum shearing tank 3, starting a colostrum shearing machine 31 to prepare colostrum, and shearing to form uniform colostrum.

(2) The compressed air storage tank 5 is opened, a fixed gas flow is output through the gas flow meter 10 with the regulating valve, compressed air is introduced into the colostrum shearing tank 3, and colostrum is supplied to the liquid inlet 81 of the gas flow nozzle 8 at a certain flow rate.

(3) Meanwhile, a fixed gas flow is output through a gas flow meter 10 with an adjusting valve, compressed air is introduced into a gas inlet 82 of the gas flow nozzle 8, colostrum is dispersed into uniform micro-droplets by utilizing the crushing effect of gas flowing through a top nozzle 83 through controlling the viscosity of colostrum liquid and the gas flow rate of the gas flow nozzle, the micro-droplets are sprayed into an outer water phase of the drying tank 4 in liquid after atomization, meanwhile, a stirrer 44 is started to disperse micro-spheres to form uniformly dispersed composite emulsion droplets, the drying temperature in the liquid is adjusted through a temperature control jacket 41 of the drying tank 4 in liquid, and volatilized organic solvent is discharged through an exhaust port 42 at the top of the drying tank 4 in liquid.

Compared with a system for treating the high-viscosity primary emulsion by spraying on the liquid surface, a large amount of polymer films appear on the liquid surface, and the dispersion is difficult, so that the microsphere yield is extremely low and is less than 20%. The utility model can not form a large amount of films, and the yield can reach about 68 percent.

The above-described embodiments are only preferred embodiments of the present invention, and are not intended to limit the present invention in any way, and other variations and modifications may be made without departing from the scope of the claims.

Claims

1. A polypeptide medicine microsphere preparation system based on submerged airflow spraying is characterized in that: including interior water phase jar (1), oil phase jar (2), colostrum shearing jar (3), drier in the liquid (4) and compressed air storage tank (5), interior water phase jar (1) and oil phase jar (2) are connected to colostrum shearing jar through interior water phase injection passageway (6) and oil phase injection passageway (7) respectively, drier in the liquid (4) bottom is equipped with air current nozzle (8), the discharge gate of colostrum shearing jar (3) and the gas outlet of compressed air storage tank (5) are connected with air current nozzle (8) through the pipeline respectively.

2. The system for preparing polypeptide medicine microspheres based on submerged airflow spraying according to claim 1, wherein: the air flow nozzle (8) consists of a liquid inlet (81), a gas inlet (82) and a top nozzle (83), a discharge hole of the colostrum shearing tank (3) is connected with the liquid inlet (81) through a pipeline, and an air outlet of the compressed air storage tank (5) is connected with the gas inlet (82) through a pipeline.

3. The system for preparing polypeptide medicine microspheres based on submerged air-flow spraying according to claim 1 or 2, wherein: a water system filter membrane for filtering the internal water phase is arranged in the internal water phase injection channel (6).

4. The system for preparing polypeptide medicine microspheres based on submerged air-flow spraying according to claim 1 or 2, wherein: an oil system filter membrane for filtering the oil phase is arranged in the oil phase injection channel (7).

5. The system for preparing polypeptide medicine microspheres based on submerged air-flow spraying according to claim 1 or 2, wherein: an oil phase pump (11) is arranged on the oil phase injection channel (7).

6. The system for preparing polypeptide medicine microspheres based on submerged air-flow spraying according to claim 1 or 2, wherein: the air flow nozzle (8) is connected with the drying tank (4) in the liquid in a sealing way through a nozzle tank bottom sealing element (9).

7. The system for preparing polypeptide medicine microspheres based on submerged air-flow spraying according to claim 1 or 2, wherein: the colostrum shearing tank (3) is provided with a colostrum shearing machine (31).

8. The system for preparing polypeptide medicine microspheres based on submerged air-flow spraying according to claim 1 or 2, wherein: the outer side of the liquid drying tank (4) is provided with a temperature control jacket (41), the top of the liquid drying tank (4) is provided with an exhaust port (42), and the exhaust port (42) is provided with a gas filter membrane (43).

9. The system for preparing polypeptide medicine microspheres based on submerged air-flow spraying according to claim 1 or 2, wherein: the liquid drying tank (4) is provided with a stirrer (44), the stirrer (44) is connected with the liquid drying tank (4) in a sealing manner, and a stirring paddle (441) of the stirrer (44) is positioned 5-10cm above the airflow nozzle.

10. The system for preparing polypeptide medicine microspheres based on submerged air-flow spraying according to claim 1 or 2, wherein: the air outlet of the compressed air storage tank (5) is also connected with the oil phase injection channel (7) through a pipeline.