An apparatus for producing liposomes

Abstract

This application relates to a liposome production and preparation apparatus, belonging to the technical field of liposomes. It includes an aqueous phase structure, an organic phase structure, a microfluidic mixing structure, a static mixing structure, an extrusion structure, and a solvent removal structure. The aqueous phase structure includes a water tank, an inlet pipe, an outlet pipe, and a first high-pressure pump. The organic phase structure includes an organic tank, an inlet pipe, an outlet pipe, and a second high-pressure pump. The microfluidic mixing structure includes a mixing pipe and a conveying pipe. The static mixing structure includes a mixing tank, a rotating rod, blades, a motor, a solenoid valve, and a first liquid outlet pipe. The extrusion structure includes an extrusion pipe and an extrusion membrane. This application solves the problem that relying on containerized material collection and transfer between processes results in production efficiency limited by process time, tank volume, and other factors. This not only makes large-scale continuous production difficult but also may cause material loss or contamination due to multiple transfers, affecting product quality stability.

Description

Technical Field

[0001] This application relates to liposomes, and more particularly to an apparatus for the production and preparation of liposomes. Background Technology

[0002] Liposomes, as novel drug delivery carriers, have been widely used in the biomedical field due to their excellent biocompatibility, targeting ability, and efficient drug encapsulation capabilities. They can encapsulate active ingredients such as vaccines, anticancer drugs, and gene therapy agents, reducing the toxic side effects of drugs on normal tissues and increasing the concentration of drugs at the lesion site, thereby enhancing the therapeutic effect. They have become a key technology carrier in vaccine development, tumor treatment, and genetic engineering.

[0003] Existing liposome production technologies employ an intermittent production model. The entire process involves multiple steps, including mixing water and lipids, hydration preparation, granulation, and desolvation. Each step requires independent containers and equipment. During the preparation and granulation process, material collection and transfer between processes rely on container loading. This results in production efficiency being limited by factors such as process time and container volume. Not only is it difficult to achieve large-scale continuous production, but multiple transfers may also cause material loss or contamination, affecting product quality stability. Utility Model Content

[0004] The purpose of this application is to provide a liposome production and preparation device that solves the problem that the reliance on container loading for material collection and transfer between processes leads to production efficiency being limited by factors such as process time and container volume. This not only makes it difficult to achieve large-scale continuous production, but also may cause material loss or contamination due to multiple transfers, affecting the stability of product quality.

[0005] The liposome production and preparation apparatus provided in this application adopts the following technical solution: it includes an aqueous phase structure, an organic phase structure, a microfluidic mixing structure, a static mixing structure, an extrusion structure, and a solvent removal structure. The aqueous phase structure includes a water tank, an inlet pipe, an outlet pipe, and a first high-pressure pump. The organic phase structure includes an organic tank, an inlet pipe, an outlet pipe, and a second high-pressure pump. The microfluidic mixing structure includes a mixing pipe and a conveying pipe. The static mixing structure includes a mixing tank, a rotating rod, blades, a motor, a solenoid valve, and a first liquid outlet pipe. The extrusion structure includes an extrusion pipe and an extrusion membrane. The solvent removal structure includes a separation tank, an inlet pipe, a second liquid outlet pipe, a separation membrane, and a discharge port. By adopting the above technical solution, when using this device, the raw materials only need to be placed inside the water tank and the organic tank respectively. The raw materials are then mixed by the first high-pressure pump and the second high-pressure pump. After mixing, the rotation of the rotating rod causes the blades to shear the liposomes, reducing the particle size of the liposomes. The extrusion membrane further restricts the size of the liposomes, ensuring that the particle size meets production requirements. The separation tank can separate the qualified liposome particles from the solution, allowing operators to collect the liposomes individually. This solves the problem of relying on container loading for material collection and transfer between processes, which leads to production efficiency being limited by process time, tank volume, and other factors. This not only makes it difficult to achieve large-scale continuous production but also may cause material loss or contamination due to multiple transfers, affecting the stability of product quality.

[0006] Preferably, the upper surface of the water bucket has a through hole and a water inlet pipe is fixedly connected thereto, the outer surface of the water bucket has a through hole and a water outlet pipe is fixedly connected thereto, and the end of the water outlet pipe away from the water bucket is connected to the suction port of the first high-pressure pump. By adopting the above technical solution, the water inlet pipe is connected to the external pipeline, and the operator only needs to control the opening or closing of the first high-pressure pump to complete the feeding and stopping of the buffer solution.

[0007] Preferably, the upper surface of the organic barrel is provided with a through hole and a feed pipe is fixedly connected thereto, the outer surface of the organic barrel is provided with a through hole and a discharge pipe is fixedly connected thereto, and the end of the discharge pipe away from the organic barrel is connected to the suction port of the second high-pressure pump. By adopting the above technical solution, the feed pipe is connected to the external pipeline, and the operator only needs to control the opening or closing of the first and second high-pressure pumps to complete the feeding and stopping of the organic solution.

[0008] Preferably, the mixing tube is Y-shaped, with one end connected to the conveying tube and the other two ends connected to the outlet of the first high-pressure pump and the outlet of the second high-pressure pump, respectively. By adopting the above technical solution, the Y-shaped mixing tube can flush out the organic solution and the buffer solution, thereby mixing the two solutions together.

[0009] Preferably, the outer surface of the mixing tank has a through hole and is fixedly connected to the end of the conveying pipe away from the mixing pipe. The inside of the mixing tank is rotatably connected to a rotating rod, and several blades are fixedly connected to the outside of the rotating rod. The outer surface of the mixing tank has a through hole and is fixedly connected to an electromagnetic valve. The end of the electromagnetic valve away from the mixing tank is connected to a first liquid outlet pipe. By adopting the above technical solution, the rotating rod can make the blades rotate, and the blades can shear the liposomes after rotation, reducing the particle size of the liposomes. The electromagnetic valve can open or close the mixing tank.

[0010] Preferably, a motor is fixedly connected to the upper surface of the mixing tank, and the output shaft of the motor passes through the mixing tank and is fixedly connected to a rotating rod; By adopting the above technical solution, the motor can provide power to the rotating rod, causing the rotating rod to rotate.

[0011] Preferably, the number of extruded films is several, and the several extruded films are all located inside the extrusion tube and fixedly connected to the extrusion tube, and the pore size of the several extruded films is different; By adopting the above technical solution, several extrusion films can be used to further screen liposomes so that the particle size of the liposomes meets the production requirements.

[0012] Preferably, one end of the extrusion tube is connected to the end of the first liquid outlet tube away from the mixing tank, the outside of the separation tank is provided with a through hole and a liquid inlet tube is fixedly connected thereto, the end of the liquid inlet tube away from the separation tank is connected to the end of the extrusion tube away from the first liquid outlet tube, the outside of the separation tank is provided with a through hole and a second liquid outlet tube is fixedly connected thereto, a separation membrane is fixedly connected inside the separation tank, and the discharge port is located on the surface of the separation tank. By adopting the above technical solution, the separation membrane is tilted in the separation tank, and the separation membrane can separate the liposomes from the solution, thereby classifying and collecting the two.

[0013] In summary, this application includes at least one of the following beneficial technical effects: 1. This liposome production and preparation device, through the design of an aqueous phase structure, an organic phase structure, a microfluidic mixing structure, a static mixing structure, an extrusion structure, and a solvent removal structure, allows the device to operate by simply placing the raw materials into a water tank and an organic tank respectively. The raw materials are then mixed by a first high-pressure pump and a second high-pressure pump. After mixing, the rotation of the rotating rod causes the blades to shear the liposomes, reducing their particle size. The extrusion membrane further restricts the liposome particle size, ensuring it meets production requirements. A separation tank separates the qualified liposome particles from the solution, allowing operators to collect the liposomes individually. This solves the problem of relying on containerized material collection and transfer between processes, which limits production efficiency due to process time and tank volume, hindering large-scale continuous production and potentially causing material loss or contamination due to multiple transfers, thus affecting product quality stability. Attached Figure Description

[0014] Figure 1 This is an axial view schematic diagram of this application; Figure 2 This is an axial view schematic diagram of the microfluidic mixing structure of this application; Figure 3 This is an axial view schematic diagram of the static hybrid structure of this application; Figure 4 For the purposes of this application Figure 3 Enlarged view of point A; Figure 5 This is a schematic diagram of the solvent removal structure of this application.

[0015] In the picture: 1. Aqueous phase structure; 2. Organic phase structure; 3. Microfluidic mixing structure; 4. Static mixing structure; 5. Extrusion structure; 6. Solvent removal structure; 101. Water tank; 102. Water inlet pipe; 103. Water outlet pipe; 104. First high-pressure pump; 201. Organic tank; 202. Feed pipe; 203. Discharge pipe; 204. Second high-pressure pump; 301. Mixing pipe; 302. Conveying pipe; 401. Mixing tank; 402. Rotating rod; 403. Blade; 404. Motor; 405. Solenoid valve; 406. First liquid outlet pipe; 501. Extrusion pipe; 502. Extrusion membrane; 601. Separation tank; 602. Liquid inlet pipe; 603. Second liquid outlet pipe; 604. Separation membrane; 605. Discharge port. Detailed Implementation

[0016] The following is in conjunction with the appendix Figure 1 - Appendix Figure 5 This application will be described in further detail below.

[0017] Example 1: A liposome production and preparation apparatus, referring to... Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5The system includes an aqueous phase structure 1, an organic phase structure 2, a microfluidic mixing structure 3, a static mixing structure 4, an extrusion structure 5, and a solvent removal structure 6. The aqueous phase structure 1 includes a water tank 101, an inlet pipe 102, an outlet pipe 103, and a first high-pressure pump 104. The organic phase structure 2 includes an organic tank 201, an inlet pipe 202, an outlet pipe 203, and a second high-pressure pump 204. The microfluidic mixing structure 3 includes a mixing pipe 301 and a conveying pipe 302. The static mixing structure 4 includes a mixing tank 401, a rotating rod 402, blades 403, a motor 404, a solenoid valve 405, and a first liquid outlet pipe 406. The extrusion structure 5 includes an extrusion pipe 501 and an extrusion membrane 502. The solvent removal structure 6 includes a separation tank 601 and an inlet pipe 602. The system includes a second liquid outlet pipe 603, a separation membrane 604, and a discharge port 605. A water tank 101 has a through hole on its upper surface, with an inlet pipe 102 fixedly connected to it. A water tank 101 also has a through hole on its outer surface, with an outlet pipe 103 fixedly connected to it. The end of the outlet pipe 103 furthest from the water tank 101 is connected to the suction port of the first high-pressure pump 104. An organic tank 201 has a through hole on its upper surface, with a feed pipe 202 fixedly connected to it. The outer surface of the organic tank 201 also has a through hole, with a discharge pipe 203 fixedly connected to it. The end of the discharge pipe 203 furthest from the organic tank 201 is connected to the suction port of the second high-pressure pump 204. A mixing pipe 301 is Y-shaped, with one end connected to a conveying pipe 302 and the other two ends connected to the first high-pressure pump 104. The outlet of the mixing tank 401 is connected to the outlet of the second high-pressure pump 204. A through hole is provided on the outer surface of the mixing tank 401, and a conveying pipe 302 is fixedly connected to one end away from the mixing pipe 301. A rotating rod 402 is rotatably connected inside the mixing tank 401. Several blades 403 are fixedly connected to the outer side of the rotating rod 402. A solenoid valve 405 is fixedly connected to the outer surface of the mixing tank 401, and the end of the solenoid valve 405 away from the mixing tank 401 is connected to the first liquid outlet pipe 406. A motor 404 is fixedly connected to the upper surface of the mixing tank 401. The output shaft of the motor 404 passes through the mixing tank 401 and is fixedly connected to the rotating rod 402. Several extrusion films 502 are present, and all of them are located inside the extrusion pipe 501 and fixedly connected. The extrusion tube 501 and several extrusion membranes 502 with varying pore sizes are connected. One end of the extrusion tube 501 is connected to the end of the first liquid outlet pipe 406 away from the mixing tank 401. A through hole is provided on the outside of the separation tank 601, and an inlet pipe 602 is fixedly connected to it. The end of the inlet pipe 602 away from the separation tank 601 is connected to the end of the extrusion tube 501 away from the first liquid outlet pipe 406. A through hole is provided on the outside of the separation tank 601, and a second liquid outlet pipe 603 is fixedly connected to it. A separation membrane 604 is fixedly connected inside the separation tank 601. A discharge port 605 is located on the surface of the separation tank 601. Through the arrangement of the aqueous phase structure 1, organic phase structure 2, microfluidic mixing structure 3, static mixing structure 4, extrusion structure 5, and solvent removal structure 6, the device can be used...By simply placing the raw materials into the water tank 101 and the organic tank 201 respectively, the raw materials can be mixed by the first high-pressure pump 104 and the second high-pressure pump 204. After mixing, the rotation of the rotating rod 402 causes the blades 403 to shear the liposomes, reducing their particle size. The extrusion membrane 502 further restricts the liposome particle size, ensuring it meets production requirements. The separation tank 601 separates the qualified liposome particles from the solution, allowing operators to collect the liposomes individually. This solves the problem of relying on containerized material collection and transfer between processes, which limits production efficiency due to process time and tank volume, hindering large-scale continuous production and potentially causing material loss or contamination due to multiple transfers, thus affecting product quality stability.

[0018] The implementation principle of this application embodiment is as follows: During use, the operator injects a buffer solution into the water tank 101 through the water inlet pipe 102 and an organic solution into the organic tank 201 through the feed pipe 202. Then, the first high-pressure pump 104 and the second high-pressure pump 204 are started. After the first high-pressure pump 104 starts, it extracts the buffer solution inside the water tank 101 and allows it to enter the mixing pipe 301. The second high-pressure pump 204 extracts the organic solution inside the organic tank 201 and allows it to enter the mixing pipe 301. The buffer solution and the organic solution then contact and collide inside the mixing pipe 301, mixing during the collision. During mixing, the liposomes inside the organic solution are sheared by collision, thereby reducing the particle size of the liposomes. The mixed solution then enters the conveying pipe 302 and then into the mixing tank 401. After entering, the motor 404 is started. The output shaft of the motor 404 causes the rotating rod 402 to rotate. After activation, the blade 403 rotates, shearing the liposomes inside the solution and further reducing their particle size. Once the liposomes have been sheared, the solenoid valve 405 opens, allowing the solution to carry the liposomes into the solenoid valve 405 and then into the extrusion tube 501. Inside the extrusion tube 501, the liposomes come into contact with the extrusion membrane 502. Under the impact of the solution, the liposomes pass through the extrusion membrane 502 and undergo further particle size adjustment. The solution then carries the liposomes with the correct particle size into the separation tank 601. Inside the separation tank 601, the solution comes into contact with the separation membrane 604 and falls to the bottom of the separation tank 601. The solution is then discharged through the second outlet pipe 603, while the liposomes are intercepted by the separation membrane 604. While on the separation membrane 604, some liposomes begin to slide and reach the discharge port 605. The liposomes then slide out of the separation membrane 604 and are collected by an external device.

Claims

1. A liposome production and preparation apparatus, comprising an aqueous phase structure (1), an organic phase structure (2), a microfluidic mixing structure (3), a static mixing structure (4), an extrusion structure (5), and a solvent removal structure (6), characterized in that: The aqueous phase structure (1) includes a water tank (101), an inlet pipe (102), an outlet pipe (103), and a first high-pressure pump (104). The organic phase structure (2) includes an organic tank (201), an inlet pipe (202), an outlet pipe (203), and a second high-pressure pump (204). The microfluidic mixing structure (3) includes a mixing pipe (301) and a conveying pipe (302). The static mixing structure (4) includes a mixing tank (401), a rotating rod (402), a blade (403), a motor (404), a solenoid valve (405), and a first liquid outlet pipe (406). The extrusion structure (5) includes an extrusion pipe (501) and an extrusion membrane (502). The solvent removal structure (6) includes a separation tank (601), an inlet pipe (602), a second liquid outlet pipe (603), a separation membrane (604), and a discharge port (605).

2. The apparatus for producing liposomes according to claim 1, wherein: The upper surface of the water bucket (101) has a through hole and is fixedly connected to the water inlet pipe (102). The outer surface of the water bucket (101) has a through hole and is fixedly connected to the water outlet pipe (103). The end of the water outlet pipe (103) away from the water bucket (101) is connected to the suction port of the first high-pressure pump (104).

3. The apparatus of claim 1, wherein: The upper surface of the organic barrel (201) has a through hole and a feed pipe (202) is fixedly connected thereto. The outer surface of the organic barrel (201) has a through hole and a discharge pipe (203) is fixedly connected thereto. The end of the discharge pipe (203) away from the organic barrel (201) is connected to the suction port of the second high-pressure pump (204).

4. The apparatus of claim 1, wherein: The mixing tube (301) is Y-shaped. One end of the mixing tube (301) is connected to the conveying tube (302), and the other two ends of the mixing tube (301) are connected to the outlet of the first high-pressure pump (104) and the outlet of the second high-pressure pump (204), respectively.

5. The apparatus of claim 1, wherein: The outer surface of the mixing tank (401) has a through hole and is fixedly connected to one end of the conveying pipe (302) away from the mixing pipe (301). The mixing tank (401) is rotatably connected to a rotating rod (402). Several blades (403) are fixedly connected to the outer side of the rotating rod (402). The outer surface of the mixing tank (401) has a through hole and is fixedly connected to an electromagnetic valve (405). The end of the electromagnetic valve (405) away from the mixing tank (401) is connected to a first liquid outlet pipe (406).

6. The apparatus of claim 1, wherein: A motor (404) is fixedly connected to the upper surface of the mixing tank (401), and the output shaft of the motor (404) passes through the mixing tank (401) and is fixedly connected to the rotating rod (402).

7. The apparatus of claim 1, wherein: The number of extruded membranes (502) is several, and the several extruded membranes (502) are all located inside the extrusion tube (501) and fixedly connected to the extrusion tube (501). The pore sizes of the several extruded membranes (502) are different.

8. The apparatus of claim 1, wherein: One end of the extrusion tube (501) is connected to the end of the first liquid outlet tube (406) away from the mixing tank (401). The outer side of the separation tank (601) is provided with a through hole and a liquid inlet tube (602) is fixedly connected. The end of the liquid inlet tube (602) away from the separation tank (601) is connected to the end of the extrusion tube (501) away from the first liquid outlet tube (406). The outer side of the separation tank (601) is provided with a through hole and a second liquid outlet tube (603) is fixedly connected. A separation membrane (604) is fixedly connected inside the separation tank (601). The discharge port (605) is opened on the surface of the separation tank (601).

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