WO2009092333A1

WO2009092333A1 - Device and process for preparing sodium alginate/chitosan slow release capsules with high efficiency

Info

Publication number: WO2009092333A1
Application number: PCT/CN2009/070212
Authority: WO
Inventors: Chunlei Fan
Original assignee: Chunlei Fan
Priority date: 2008-01-17
Filing date: 2009-01-19
Publication date: 2009-07-30
Also published as: CN201105216Y

Abstract

A device and a process for preparing sodium alginate/chitosan slow release capsules. The device comprises an emulsifier device (A) capable of automatically stirring and grinding and a centrifugal screen pelletizer (B) connected with each other by a guide pipe (11). The process comprises emulsification, pelletization, conditioning and other steps by use of the device.

Description

Equipment and preparation process for efficiently preparing sodium alginate/chitosan sustained-release microcapsule

The invention discloses an apparatus and a preparation process for preparing sodium alginate/chitosan sustained-release microcapsules. Background technique

Sodium alginate/chitosan sustained release microcapsules have good biocompatibility and mechanical strength and are an excellent sustained release drug delivery system widely used in drug controlled release vehicles, gene delivery vehicles, immunoisolation and Artificial organs, cell culture microreactors, environmental purification and other aspects. At present, the preparation methods of sodium alginate/chitosan sustained-release microcapsules mainly include dripping method, spray calligraphy and emulsification method. The drip method is mainly prepared by using a syringe drop. The microcapsules are formed by drop, and the efficiency is low. The particle size of the sustained release microcapsules is limited by the inner diameter of the syringe needle and the viscosity of the solution. The spray method mainly uses a coaxial jet device and an electrostatic titration device. The microcapsules prepared by this method have larger particle size, poor microsphere shape and smoothness, and the particle size of the sustained release microcapsules is also affected by the inner diameter of the nozzle and the viscosity of the solution. Restricted, and the equipment is complex, it is difficult to scale production. Later, scholars invented the emulsification method, which can carry out large-scale industrial production. The main disadvantage is that the gel bead shape is unstable, and the particle size distribution of the sustained-release microcapsules is wide and distributed in multiple intervals, and the preparation process is relatively complicated. In the preparation of calcium alginate beads, since the calcium salt is difficult to disperse uniformly, the microencapsulated material is easily lost, resulting in a lower encapsulation efficiency, and thus cannot satisfy the substance activity and the uniformity of the sustained release microcapsules in the fields of medicine and chemical industry. Therefore, improving the drug encapsulation efficiency and formulation stability is an urgent problem to be solved in the research of sodium alginate/chitosan sustained release preparation.

Summary of the invention

The technical problem to be solved by the present invention is to overcome the defects of the prior art mentioned above, and provide an apparatus and a preparation process for efficiently and rapidly preparing sodium alginate/chitosan sustained-release microcapsules, and improving the microcapsule drug content, encapsulation efficiency and Uniformity of microcapsules, simplifying the preparation process, improving production efficiency and production Scale. To this end, the present invention adopts the following technical solutions:

An apparatus for efficiently preparing sodium alginate/chitosan sustained-release microcapsules, characterized by comprising an emulsifier device and a centrifugal sieve granulator which are automatically connected to each other by a draft tube, the emulsifier device comprising The emulsifying tank and the emulsifier motor and the three-way valve mounted thereon, the emulsification tank is divided into three parts, the upper part is a mixing tank with a feeding port, the middle part is a crusher, and the lower part is provided The emulsification tank of the discharge port, the three-way valve is installed at the discharge port and respectively connected with a return pipe and a draft tube, the output shaft of the emulsifier motor extends into the emulsion tank, and the output shaft is located at the mixing tank. The mixing tank is agitating the paddle, and the output shaft is located at the miller with a spiral grooved grinding rod matched with the inner wall of the mill, and the output shaft is located at the emulsion tank and is connected with the emulsifier pool stirring paddle.

The centrifugal sieve granulator comprises a curing reaction tank, the upper part of the curing reaction tank is connected with the draft tube, and the collecting tube is connected at the bottom, and the tank is provided with a sieve barrel with a plurality of sieve holes on the side wall, and the curing reaction tank The top is provided with a bucket-shaped feeding tube which is connected with the sieve barrel, and the sieve barrel is mounted on the rotating shaft, and the rotating shaft is connected through the curing reaction tank and the external speed regulating motor.

The curing reaction tank of the centrifugal sieve granulator is provided with a circle of waterfall grooves around the inner wall of the tank, and the waterfall tank is higher than the working surface of the sieve hole, and the curing reaction tank is externally connected with a circulation tube with a liquid pump, and one end of the circulation tube The curing reaction tank is connected to the waterfall tank, and the other end is connected to the bottom of the curing reaction tank; a filter screen is arranged at the bottom of the curing reaction tank and the connection of the circulation pipe.

The rotating shaft is provided with a stirring paddle, and the stirring paddle is located below the screen barrel.

The curing reaction tank is a split structure, which is formed by docking the detachable top cover and the can body. The screen barrel and the rotating shaft are detachably connected.

The preparation process for efficiently preparing sodium alginate/chitosan sustained-release microcapsules, using the above-mentioned equipment for efficiently preparing sodium alginate/chitosan sustained-release microcapsules adopts the following steps: First 歩, emulsification step: dissolving a fat-soluble or water-soluble drug in a sodium alginate solution as a dispersing agent, and preparing a medicated emulsified droplet or suspension by an automatic stirring ore emulsification device;歩, granulation process: The first mash preparation solution is poured into a centrifugal sieve granulator, which is centrifuged and combined with a calcium chloride chitosan solution to form a drug-containing sodium alginate/chitosan sustained-release micro bag;

The third step, the finishing step: curing, collecting, washing the second mash to obtain a preparation, less than or equal to

Dry at 55 ° C.

It also includes the following steps:

Prepare the following solutions in pharmaceutical water:

Liquid A: mass percentage of 1.5% sodium alginate solution + mass percentage of 2% drug; liquid B: volume fraction of 1% acetic acid + mass fraction of 1% calcium chloride + mass fraction 0.5% chitosan solution.

After adding the liquid A to the emulsifier, it is fully suspended and emulsified by circulating stirring and milling. The speed of the emulsified motor is 500r/min-4000r/min, and the emulsification time is 30min-60min.

Adding liquid B to the curing reaction tank of the centrifugal sieve granulator, the liquid A containing the emulsified drug enters the sieve barrel of the centrifugal sieve granulator through the diversion tube, and is centrifugally extracted into the curing reaction tank, and B The liquid-binding reaction generates a sodium alginate/chitosan sustained-release microcapsule; the speed of the speed regulating motor of the centrifugal sieve granulator is 300r/min-1000r/min.

The invention has high automation degree by new equipment and preparation process, and can quickly and efficiently prepare sodium alginate/chitosan sustained release microcapsule with good spherical shape, high yield, high surface smoothness and narrow particle size distribution, and is easy to be prepared. Industrial production. In addition, the process of preparing the sustained-release microcapsules can also control the size of the microcapsules by adjusting the motor rotation speed, and prepare sodium alginate/chitosan sustained-release microcapsules with different particle diameters to meet the actual needs. The invention will now be further described in conjunction with the drawings and specific embodiments.

DRAWINGS

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic view showing the structure of an emulsifier A and a centrifugal granulator B according to the present invention.

In the figure, 1, the emulsifier motor, 2, the mixing tank, 3, the mill, 4, the grinding tank with the spiral groove, 5, the emulsification tank, 6, the feed port, 7, the mixing tank stirring paddle, 8. Emulsifying tank stirring paddle, 9, three-way valve, 10, return pipe, 11, diversion pipe, 12, speed regulating motor, 13, feed pipe, 14, curing reaction tank, 15, sieve drum, 16, stirring Paddle, 17, inlet tube, 18, waterfall tank, 19, liquid level, 20, filter screen, 21, pump, 22, circulation tube, 23, collection tube.

detailed description

As shown in FIG. 1, an apparatus for efficiently preparing sodium alginate/chitosan sustained-release microcapsules, comprising an emulsifier device and a centrifugal sieve granulator which are automatically connected to each other by a draft tube 11 and an emulsifier device The invention comprises an emulsifying tank and an emulsifier motor 1 and a three-way valve 9 mounted thereon, the emulsifier tank is divided into upper and lower parts, the upper part is a mixing tank 2 with a feeding port 6, the middle part is a crusher 3, and the lower part For the emulsification tank 5 provided with the discharge port, the three-way valve 9 is installed at the discharge port and is respectively connected with the return pipe 10 and the draft tube 11, and the output shaft of the emulsifier motor 1 extends into the emulsification tank, and the output shaft is located at the mixing There is a mixing tank stirring paddle 7 at the leveling tank 2, and the output shaft is located at the miller with a spiral grooved grinding rod 4 matched with the inner wall of the mill, and the output shaft is located at the emulsification tank 5 and is connected with the emulsification tank. Stir the paddle 8. The centrifugal sieve granulator comprises a curing reaction tank 14, the upper part of the curing reaction tank 14 is connected with the draft tube 11, and the bottom is connected with a collecting tube 23, and the tank is provided with a sieve barrel 15 having a plurality of sieve holes on the side wall, and solidified. The top of the reaction tank 14 is provided with a bucket-shaped feed pipe 13 communicating with the sieve drum 15, and the sieve drum 15 is mounted on the rotating shaft, and the rotating shaft is connected through the curing reaction tank 14 and the external speed regulating motor 12. The curing reaction tank 14 of the centrifugal sieve granulator is provided with a circle of waterfall grooves 18 around the inner wall of the tank, the waterfall tank 18 is higher than the working surface of the screen hole, and the curing reaction tank 14 is connected with a pumping liquid. The circulation pipe 22 of the pump 21, the end of the circulation pipe 22 is connected to the curing reaction tank 14 and connected to the waterfall tank 18, and the other end is connected to the bottom of the curing reaction tank 14. The bottom of the curing reaction tank 14 and the circulation pipe 22 are provided with a filter screen. Web 20. A stirring paddle 16 is mounted on the rotating shaft, and the stirring paddle 16 is located below the sieve drum. The curing reaction tank 14 has a split structure and is formed by a detachable top cover and a can body. There is a detachable connection between the sieve drum 15 and the rotating shaft.

Preparation process of high-efficiency preparation of sodium alginate/chitosan sustained-release microcapsules:

Embodiment 1

Prepare the following solutions in pharmaceutical water:

Solution A: Mass percentage of 1.5% sodium alginate solution + mass percentage of 2% curcumin; Solution B: acetic acid with a volume fraction of 1% + calcium chloride with mass fraction of 1% + mass fraction a 0.5% chitosan solution;

When the three-way valve 9 is turned to the state A1, the liquid A is added to the mixing tank 2 at the upper portion of the emulsifying tank through the feeding port 6, and the emulsifier motor 1 is turned on, the rotation speed is 1000r/min, and the mixing tank stirring paddle 7 is stirred and pushed. The pulverizer 3 entering the middle of the emulsification tank is crushed by the sifting tank with the spiral groove and pushed into the emulsification tank 5 at the lower part of the emulsification tank, and the emulsification tank stirring paddle 8 is stirred one by one. At this time, the three-way valve 9 at the discharge port is turned to the state A2 to turn on the return pipe 10, and the liquid A is returned to the upper portion of the emulsion tank to be stirred and crushed, and fully suspended for 30 minutes to prepare a curcumin sodium alginate suspension. .

The liquid B is supplied to the solidification reaction tank 14 of the centrifugal sieve granulator through the inlet pipe 17. Subsequently, the three-way valve 9 is turned to the state A4 to turn on the draft tube 11, and the obtained curcumin sodium alginate suspension sequentially flows into the bucket-shaped feed tube 13 and the sieve barrel 15 of the centrifugal sieve granulator. The pumping pump 21 is turned on to pump the liquid B in the curing reaction tank 14 to the rising tank 18 through the circulation pipe 22 and overflow to form a solution curtain. Turn on the speed regulating motor 12, the rotation speed is 400r/min, centrifuge the curcumin sodium alginate suspension into the curing reaction tank 14, and react with the B liquid. A curcumin-containing sodium alginate/chitosan sustained release microcapsule is produced.

The B liquid consumed can be continuously replenished from the inlet pipe 17 throughout the production process. The microcapsule product can be collected from collection tube 23. The collected microcapsule product was placed in solution B for further 30 minutes, and then the solution was sieved, washed with water, and dried by blowing at 55 ° C to prepare a microcapsule product. The production can work continuously without parking. If it is necessary to produce particles of different sizes, simply adjust the motor speed or change the diameter of the different types of sieve drums and the aperture of the sieve holes.

Embodiment 2

Prepare the following solutions in pharmaceutical water:

Liquid A: mass percentage of 1.5% sodium alginate solution + mass percentage of 2% zedoary turmeric oil; liquid B: volume fraction of 1% acetic acid + mass fraction of 1% calcium chloride + mass fraction It is a 0.5% chitosan solution.

When the three-way valve 9 is turned to the state A1, the liquid A is added to the mixing tank 2 at the upper portion of the emulsifying tank through the feeding port 6, and the emulsifier motor 1 is turned on, the rotation speed is 1000r/min, and the mixing tank stirring paddle 7 is stirred and pushed. The pulverizer 3 entering the middle of the emulsification tank is crushed by the sifting tank with the spiral groove and pushed into the emulsification tank 5 at the lower part of the emulsification tank, and the emulsification tank stirring paddle 8 is stirred one by one. At this time, the three-way valve 9 at the discharge port is turned to the state A2 to be connected to the return pipe 10, and the liquid A is returned to the upper portion of the emulsion tank for circulation stirring and grinding, and fully suspended for 30 minutes to prepare a sorghum oil sodium alginate suspension. .

The liquid B is supplied to the solidification reaction tank 14 of the centrifugal sieve granulator through the inlet pipe 17. Subsequently, the three-way valve 9 is turned to the state A4 to turn on the draft tube 11, and the prepared zedoary turmeric sodium alginate suspension sequentially flows into the bucket-shaped feed tube 13 and the sieve barrel 15 of the centrifugal sieve granulator. The pumping pump 21 is turned on to pump the liquid B in the curing reaction tank 14 to the rising tank 18 through the circulation pipe 22 and overflow to form a solution curtain. Turn on the speed regulating motor 12, the rotation speed is 400r/min, centrifuge the sorghum oil sodium alginate suspension into the curing reaction tank 14, and react with the B liquid. The sorghum oil sodium alginate/chitosan sustained release microcapsules were prepared.

The B liquid consumed can be continuously replenished from the inlet pipe 17 throughout the production process. The microcapsule product can be collected from collection tube 23. The collected microcapsule product was placed in solution B for further 30 minutes, then the solution was sieved, washed with water, and dried at 45 ° C to form a microcapsule product. The production can work continuously without parking. If it is necessary to produce particles of different sizes, simply adjust the motor speed or change the diameter of the different types of sieve drums and the aperture of the sieve holes.

The embodiments described above are merely preferred embodiments of the present invention, and the substantial features and significant advantages of the present invention have been disclosed, and are not intended to limit the structure of the present invention in any way. Any simple modifications, equivalent changes and modifications of the above embodiments in accordance with the technical spirit of the present invention fall within the scope of the present invention.

Claims

Claim

1. An apparatus for efficiently preparing sodium alginate/chitosan sustained-release microcapsules, characterized by comprising an emulsifier device and a centrifugal sieve granulator capable of automatically stirring and pulverizing and connecting through a draft tube (11), The emulsifier device comprises an emulsification tank and an emulsifier motor (1) and a three-way valve (9) mounted thereon, the emulsification tank is divided into three parts, the upper part is provided with a feed port (6) The mixing tank (2), the middle part is a crusher (3), and the lower part is an emulsion tank (5) having a discharge port, and the three-way valve (9) is installed at the discharge port and respectively connected with a return pipe (10), the draft tube (11), the output shaft of the emulsifier motor (1) extends into the emulsion tank, and the output shaft is located at the mixing tank (2) with a mixing tank stirring paddle (7), and the output shaft is located The mill has a grinding rod (4) with a spiral groove matched with the inner wall of the mill, and the output shaft is located at the emulsion tank (5) and is connected with an emulsion tank stirring paddle (8).

2. The apparatus for efficiently preparing sodium alginate/chitosan sustained release microcapsule according to claim 1, wherein said centrifugal sieve granulator comprises a curing reaction tank (14), and a curing reaction tank (14). The upper part is connected to the draft tube (11), and the bottom is connected with a collecting tube (23). The tank is provided with a sieve barrel (15) having a plurality of sieve holes on the side wall, and a curing reaction tank (14) is provided at the top of the reaction tank (14). A bucket-shaped feed pipe (13) communicating with the sieve drum (15), the sieve drum (15) is mounted on the rotating shaft, and the rotating shaft is connected through the curing reaction tank (14) and an external speed regulating motor (12).

The apparatus for efficiently preparing sodium alginate/chitosan sustained-release microcapsule according to claim 2, characterized in that the curing reaction tank (14) of the centrifugal sieve granulator is provided with a circle around the inner wall of the tank. The waterfall trough (18), the waterfall trough (18) is higher than the working surface of the screen hole, and the curing reaction tank (14) is externally connected with a circulation pipe (22) with a liquid pump (21), and the circulation pipe (22) is end The curing reaction tank (14) is connected to the waterfall tank (18), and the other end is connected to the bottom of the curing reaction tank (14); the bottom of the curing reaction tank (14) and the circulation pipe (22) are provided with a filtering screen ( 20).

4. The high-efficiency preparation of sodium alginate/chitosan sustained-release microcapsule according to claim 2 or The utility model is characterized in that the rotating shaft is provided with a stirring paddle (16), and the stirring paddle (16) is located below the screen barrel.

The apparatus for efficiently preparing sodium alginate/chitosan sustained-release microcapsule according to claim 4, wherein said curing reaction tank (14) is a split structure, and a removable top cover and a can It is made up of the body and the butt.

The apparatus for efficiently producing sodium alginate/chitosan sustained release microcapsule according to claim 4, wherein the sieve drum (15) and the rotating shaft are detachably connected.

7. A process for efficiently preparing a sodium alginate/chitosan sustained-release microcapsule, which is characterized by using the device for efficiently preparing sodium alginate/chitosan sustained-release microcapsule according to any one of claims 1 to 7 and adopting The following steps:

First 歩, emulsification step: dissolving a fat-soluble or water-soluble drug in a sodium alginate solution as a dispersing agent, and preparing a medicated emulsified droplet or suspension by an automatic stirring ore emulsification device;歩, granulation process: The first mash preparation solution is poured into a centrifugal sieve granulator, which is centrifuged and combined with a calcium chloride chitosan solution to form a drug-containing sodium alginate/chitosan sustained-release micro Sac

Third, finishing step: The preparation obtained by solidifying, collecting, and washing the second crucible is dried with air of 55 ° C or less.

8. The process for efficiently preparing a sodium alginate/chitosan sustained release microcapsule according to claim 7, which further comprises the following steps:

Prepare the following solutions in pharmaceutical water:

9. The process for efficiently preparing sodium alginate/chitosan sustained-release microcapsule according to claim 8, characterized in that after adding the liquid A to the emulsifier, it is fully suspended and emulsified by circulating stirring and milling. The speed of the emulsified motor is 500r/min-4000r/min, and the emulsification time is 30min-60min.

10. The process for efficiently preparing a sodium alginate/chitosan sustained-release microcapsule according to claim 9, wherein the liquid B is added to a curing reaction tank of a centrifugal sieve granulator, and the drug-containing emulsified The liquid A enters the sieve barrel of the centrifugal sieve granulator through the diversion tube, is centrifugally extracted into the curing reaction tank, and combines with the liquid B to form a drug-containing sodium alginate/chitosan sustained-release microcapsule; The speed of the speed regulating motor of the machine is 300r/min-1000r/min.