Mixing device

By designing a mixing device with a preset angle inlet channel, the problem of low fluid mixing efficiency in liposome preparation in microfluidic technology is solved, efficient fluid mixing is achieved, and the efficiency and efficiency of liposome preparation are improved. Cost effective.

CN222369006UActive Publication Date: 2025-01-21ASYMCHEM LIFE SCI TIANJIN
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Patent Information

Application Number
CN202422994727.8
Authority / Receiving Office
CN · China
Patent Type
Utility models(China)
Current Assignee / Owner
Filing Date
2024-12-05
Publication Date
2025-01-21
Estimated Expiration
2034-12-05

AI Technical Summary

Technical Problem

In liposome preparation, microfluidic control technology has low mixing efficiency and high cost in the preparation process.

Method used

A mixing device is designed, which includes a mixing body with a liquid outlet channel and a liquid inlet structure. The liquid inlet structure consists of two liquid inlet channels arranged at a preset angle. The liquid outlet channel is located between the two liquid inlet channels. The liquid outlet ends of the liquid inlet channels intersect and are connected, and the liquid outlet channel is connected to the intersection position of the two liquid inlet channels.

Benefits of technology

By increasing the contact area between fluids and accelerating the molecular diffusion process, the fluids are promoted to generate turbulence at the intersection, which significantly improves the mixing efficiency and achieves efficient mixing of the water phase and ethanol phase solutions at the intersection.

✦ Generated by Eureka AI based on patent content.

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Abstract

The utility model provides a mixing device. The mixing device comprises a mixing body, the mixing body is provided with a liquid outlet channel and a liquid inlet structure, the liquid inlet structure comprises two liquid inlet channels which are arranged at a preset included angle, the liquid outlet channel is located between the two liquid inlet channels, the liquid outlet ends of the two liquid inlet channels intersect and are communicated, and the liquid outlet channel is communicated to the intersection position of the two liquid inlet channels. The mixing device provided by the technical scheme of the utility model can solve the problem that the fluid mixing efficiency is relatively low when the liposome is prepared by adopting a microfluidic technology.
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Description

Technical Field

[0001] The utility model relates to the technical field of biological preparation equipment, in particular to a mixing device. Background Art

[0002] Liposomes, as closed vesicles composed of phospholipid bilayers, have a structure similar to that of cell membranes, which makes them play an important role in drug delivery systems. They can not only accommodate water-soluble and fat-soluble drugs, but also precisely control the release rate of drugs and targeted delivery to specific tissues or cells by adjusting lipid composition, particle size and surface properties. Traditional liposome preparation methods, such as thin film hydration method, reverse phase evaporation method and solvent injection method, however, traditional macroscopic large-volume liposome preparation methods face problems such as huge material consumption, low efficiency and process scale-up challenges during the research and development stage. These methods often have cumbersome steps, are difficult to automate, and are not suitable for large-scale production. While laboratory-scale liposome preparation usually relies on manual operation and small equipment, industrial production needs to consider multiple factors such as equipment compatibility, process parameter optimization, cost-effectiveness and quality control. Specifically: 1) Equipment compatibility: Laboratory equipment limits the potential for large-scale production, while industrial equipment has limitations in matching manufacturing capacity with liposome size and stability; 2) Process parameter optimization: When production is scaled up, changes in equipment size and pipeline size require precise adjustment of key parameters such as mixing speed, temperature, and pressure to ensure the consistency of liposome quality and performance; 3) Cost-effectiveness: High cost and complex operations, such as thin film hydration and reverse evaporation, require large amounts of organic solvents, and residual solvents may pose a safety risk; 4) Quality control: Non-continuous production processes make process control difficult and quality parameters fluctuate, affecting the process adaptability of different materials and formulations, and thus affecting product quality. All of the above constitute bottlenecks in traditional liposome preparation methods.

[0003] In this context, microfluidics, as an emerging technology that can manipulate microscale fluids, has brought unprecedented opportunities to the field of liposome preparation. Microfluidics uses channels of micrometer size, such as pipes several hundred micrometers wide, to mix, separate, screen, and other processes through the laminar flow characteristics of fluids in microscale channels. Compared with traditional methods, the application of microfluidics in liposome production has greatly reduced reagent consumption, simplified the operation process, improved the degree of automation, and reduced production costs. At the same time, the equipment has a high degree of integration and is easy to cascade with subsequent purification and online detection systems, which provides the possibility for high-throughput screening and continuous preparation of liposomes, and can reduce material requirements by several orders of magnitude, and complete the rapid screening of liposomes with different prescriptions in a short time. However, since the fluid in the microfluidic channel is usually in a laminar state, this is conducive to the precise control of fluid flow and reaction conditions, but under laminar conditions, mass transfer between fluids mainly depends on diffusion, and diffusion may be a slow process at the microscale, especially when the flow channel is long or the flow rate is slow, resulting in low mixing efficiency of the fluid. Utility Model Content

[0004] The main purpose of the utility model is to provide a mixing device, which can solve the problem of low fluid mixing efficiency when preparing liposomes using microfluidic technology.

[0005] In order to achieve the above-mentioned purpose, the utility model provides a mixing device, including: a mixing body, having a liquid outlet channel and a liquid inlet structure, the liquid inlet structure including two liquid inlet channels arranged at a preset angle, the liquid outlet channel is located between the two liquid inlet channels, the liquid outlet ends of the two liquid inlet channels intersect and are connected, and the liquid outlet channel is connected to the intersection of the two liquid inlet channels.

[0006] Furthermore, the angle between the liquid inlet channel and the liquid outlet channel is α, and the value range of α is 30°~75°; and / or, the two liquid inlet channels are axially symmetrically arranged about the central axis of the liquid outlet channel.

[0007] Furthermore, the mixing body also has a first interface and a second interface, the liquid outlet channel is connected to a first interface, and each liquid inlet channel is connected to a second interface respectively.

[0008] Furthermore, the mixing device also includes a liquid inlet pipe, a liquid outlet pipe, a first connecting piece and a second connecting piece. The liquid inlet pipe is connected to the liquid inlet channel, the first connecting piece is correspondingly arranged to the liquid inlet pipe, the liquid inlet pipe is connected to the second interface through the first connecting piece, the liquid outlet pipe is connected to the liquid outlet channel, the second connecting piece is correspondingly arranged to the liquid outlet pipe, and the liquid outlet pipe is connected to the first interface through the second connecting piece.

[0009] Furthermore, the first connecting piece is sleeved on the liquid inlet pipe and fixedly connected to the liquid inlet pipe, both ends of the liquid inlet pipe protrude from the first connecting piece, and one end portion of the liquid inlet pipe located in the second interface extends into the liquid inlet channel, and the second connecting piece is sleeved on the liquid outlet pipe and fixedly connected to the liquid outlet pipe, both ends of the liquid outlet pipe protrude from the second connecting piece, and one end portion of the liquid outlet pipe located in the first interface extends into the liquid outlet channel.

[0010] Furthermore, the first connecting member is threadedly connected to the second interface, and the second connecting member is threadedly connected to the first interface.

[0011] Furthermore, the mixing device also includes a first seal and a second seal, the first seal is arranged corresponding to the liquid inlet pipe, the first seal is sleeved on the liquid inlet pipe, the first seal is located between the first connecting member and the liquid inlet channel, the first seal is sealingly connected to the liquid inlet pipe, the first connecting member presses the first seal so that the end of the first seal facing away from the first connecting member forms a sealing fit with the bottom of the second interface, the second seal is sleeved on the liquid outlet pipe, the second seal is located between the second connecting member and the liquid outlet channel, the second seal is sealingly connected to the liquid outlet pipe, and the second connecting member presses the second seal so that the end of the second seal facing away from the second connecting member forms a sealing fit with the bottom of the first interface.

[0012] Furthermore, both the first sealing member and the second sealing member are conical structures, the small diameter end of the first sealing member faces the first connecting member, and the small diameter end of the second sealing member faces the second connecting member.

[0013] Furthermore, the inner wall of the liquid outlet channel is provided with a hydrophilic coating, and the inner wall of the liquid inlet channel is provided with a hydrophobic coating.

[0014] Furthermore, the mixing body includes a mixing part and a connecting part, the liquid outlet channel and the liquid inlet structure are both arranged on the mixing part, the mixing part is connected to the connecting part, and along the first direction, the connecting part has a first end and a second end arranged opposite to each other, and the first end and the second end are both provided with at least one connecting hole.

[0015] By applying the technical solution of the utility model, a liquid outlet channel and a liquid inlet structure are provided, and the liquid inlet structure includes two liquid inlet channels arranged at a preset angle, the liquid outlet ends of the two liquid inlet channels intersect and are connected, and the liquid outlet channel is connected to the intersection of the two liquid inlet channels. Through the above arrangement, the contact area between the fluids can be increased, the molecular diffusion process can be accelerated, and sufficient turbulence can be generated at the intersection of the fluids, thereby promoting local mixing, thereby improving the mixing efficiency, and achieving orderly and efficient mixing of the aqueous phase and the ethanol phase solution at the intersection. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The drawings constituting part of the present invention are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation on the present invention. In the drawings:

[0017] Figure 1 A perspective view of a hybrid body according to an embodiment of the present invention is shown;

[0018] Figure 2 A partial structural schematic diagram of a hybrid body of an embodiment of the utility model is shown;

[0019] Figure 3 Shows Figure 2 A schematic structural diagram of the hybrid body from another angle;

[0020] Figure 4 A partial structural schematic diagram of a mixing device according to an embodiment of the utility model is shown.

[0021] The above drawings include the following reference numerals:

[0022] 10. Mixing body; 11. Liquid outlet channel; 12. Liquid inlet channel; 13. First interface; 14. Second interface; 15. Mixing part; 16. Connecting part; 17. Connecting hole; 20. Liquid outlet pipe; 30. Second connecting piece; 40. Second sealing piece. DETAILED DESCRIPTION

[0023] It should be noted that, in the absence of conflict, the embodiments and features of the embodiments of the present invention can be combined with each other. The present invention will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0024] See also Figures 1 to 4 As shown, the utility model provides a mixing device, which includes: a mixing body 10, having a liquid outlet channel 11 and a liquid inlet structure, the liquid inlet structure including two liquid inlet channels 12 arranged at a preset angle, the liquid outlet channel 11 is located between the two liquid inlet channels 12, the liquid outlet ends of the two liquid inlet channels 12 intersect and are connected, and the liquid outlet channel 11 is connected to the intersection of the two liquid inlet channels 12.

[0025] In this embodiment, the two liquid inlet channels 12 of the liquid inlet structure are used to circulate the aqueous phase solution and the ethanol phase solution respectively. The two phase solutions are mixed at the intersection of the liquid outlet ends of the two liquid inlet channels 12, and the phospholipid components in the ethanol phase solvent are assembled to form a lipid bilayer membrane, which is curled and packaged with the aqueous phase components. The liposome vesicle suspension finally formed flows out through the liquid outlet channel 11 and is collected in a container. The liquid outlet channel 11 is located between the two liquid inlet channels 12, and the two liquid inlet channels 12 are arranged at a preset angle, and the three form an arrow-shaped structure. Through the above arrangement, the contact area between the fluids can be increased, the molecular diffusion process can be accelerated, and the fluids can generate sufficient turbulence at the intersection, promote local mixing, and then improve the mixing efficiency, so as to achieve orderly and efficient mixing of the aqueous phase and the ethanol phase solution at the intersection. In addition, the two liquid inlet channels 12 intersect at a certain angle. When the aqueous phase solution and the ethanol phase solution reach the intersection of the two liquid inlet channels 12, additional shear force will be generated. This shear force helps to destroy large particles in the fluid, accelerate the reorganization of phospholipid molecules and the formation of liposomes, thereby improving the formation efficiency and encapsulation rate of liposomes.

[0026] In one embodiment, the cross-sections of the liquid inlet channel 12 and the liquid outlet channel 11 may be circular, square or irregular.

[0027] In one embodiment, there are multiple liquid outlet channels 11 and multiple liquid inlet structures, and the multiple liquid outlet channels 11 and the multiple liquid inlet structures are arranged in a one-to-one correspondence.

[0028] See also Figures 1 to 3 As shown, in one embodiment of the present invention, the angle between the liquid inlet channel 12 and the liquid outlet channel 11 is α, and the value range of α is 30°~75°.

[0029] The above arrangement, on the one hand, helps to form a more effective and uniform mixing, and on the other hand, can ensure that the aqueous phase solution and the ethanol phase solution generate moderate shear force at the mixing point, which helps to break up the agglomeration of liposome precursors and promote the uniform assembly of the phospholipid bilayer, thereby forming liposomes with smaller particle size and more uniformity.

[0030] See also Figures 1 to 4 As shown, in one embodiment of the present invention, the two liquid inlet channels 12 are axially symmetrically arranged about the central axis of the liquid outlet channel 11 .

[0031] In this embodiment, the two liquid inlet channels 12 are axially symmetrically arranged about the central axis of the liquid outlet channel 11. On the one hand, the aqueous phase solution and the ethanol phase solution can be mixed at the intersection to form more uniform liposome vesicles, thereby improving the uniformity and efficiency of drug encapsulation. On the other hand, at the intersection, the interaction between the aqueous phase solution and the ethanol phase solution generates a shear force, and the axially symmetrical design helps to maintain the balance of this shear force at the intersection, avoiding local turbulence of the fluid, promoting the orderly assembly of phospholipid molecules, and forming liposomes with smaller particle size and more uniform distribution.

[0032] See also Figures 1 to 4 As shown, in one embodiment of the present invention, the mixing body 10 further has a first interface 13 and a second interface 14 , the liquid outlet channel 11 is connected to a first interface 13 , and each liquid inlet channel 12 is connected to a second interface 14 .

[0033] In this embodiment, the first interface 13 is provided, on the one hand, as a connection point between the liquid outlet channel 11 and an external collection device or subsequent processing equipment, ensuring that the mixed fluid can be discharged in a controllable manner, avoiding the retention or backflow of the mixture at the outlet, and ensuring the continuity of the fluid from mixing to collection. On the other hand, it is convenient to connect with external equipment (such as a filtration system, a detection device), so that the device can be applied to a continuous flow process and improve production efficiency. The second interface 14 can be used as a connection point between the liquid inlet channel 12 and an external pipeline, ensuring that the aqueous phase solution and the ethanol phase solution can enter the liquid inlet channel 12 at an accurate speed and direction.

[0034] See also Figures 1 to 4 As shown, in one embodiment of the utility model, the mixing device also includes a liquid inlet pipe, a liquid outlet pipe 20, a first connecting member and a second connecting member 30, the liquid inlet pipe is connected to the liquid inlet channel 12, the first connecting member is arranged corresponding to the liquid inlet pipe, the liquid inlet pipe is connected to the second interface 14 through the first connecting member, the liquid outlet pipe 20 is connected to the liquid outlet channel 11, the second connecting member 30 is arranged corresponding to the liquid outlet pipe 20, and the liquid outlet pipe 20 is connected to the first interface 13 through the second connecting member 30.

[0035] In this embodiment, the setting of the liquid inlet pipe can realize the delivery of aqueous phase solution and ethanol phase solution into the two liquid inlet channels 12 respectively, the setting of the liquid outlet pipe 20 can output the mixed liquid out of the mixing body 10, the setting of the first connecting piece can realize the connection between the liquid inlet pipe and the second interface 14, and the setting of the second connecting piece 30 can realize the connection between the liquid outlet pipe 20 and the first interface 13.

[0036] Specifically, both the aqueous phase solution and the ethanol phase solution can be pushed by a syringe of a specific specification through a syringe pump and injected into the liquid inlet channel 12 through the liquid inlet tube. The ethanol phase solution includes phospholipids (including but not limited to soybean lecithin of model TP12-S100, egg yolk lecithin PL-100M, distearoyl phosphatidylcholine, high-purity hydrogenated soybean lecithin, dipalmitoyl phosphatidylcholine, dioleoyl phosphatidylcholine), cholesterol and other active pharmaceutical ingredients with good fat solubility (including but not limited to doxorubicin, irinotecan, dexamethasone, tacrolimus, etc.). The aqueous phase solution includes osmotic pressure regulators, ammonium sulfate, and water-soluble drug solutions (including but not limited to amikacin sulfate, polymyxin, ganoderma lucidum polysaccharide, levofloxacin, etc.).

[0037] In one embodiment, the inner diameter of the liquid inlet pipe and the liquid outlet pipe 20 are both in the range of 0.1 mm to 5.0 mm. The liquid inlet pipe and the liquid outlet pipe 20 can be made of stainless steel or polyetheretherketone (PEEK) material.

[0038] It should be noted that the mixing device of the present application can enhance the microfluidic mixing effect and shear force while achieving high-throughput screening of liposomes, and can continuously prepare large-volume liposome vesicle samples.

[0039] See also Figures 1 to 4 As shown, in one embodiment of the utility model, the first connecting piece is sleeved on the liquid inlet pipe and fixedly connected to the liquid inlet pipe, both ends of the liquid inlet pipe protrude from the first connecting piece, and one end portion of the liquid inlet pipe located in the second interface 14 extends into the liquid inlet channel 12, the second connecting piece 30 is sleeved on the liquid outlet pipe 20 and fixedly connected to the liquid outlet pipe 20, both ends of the liquid outlet pipe 20 protrude from the second connecting piece 30, and one end portion of the liquid outlet pipe 20 located in the first interface 13 extends into the liquid outlet channel 11.

[0040] The above arrangement makes it convenient for the operator to replace or clean the liquid inlet pipe and the liquid outlet pipe 20 without disassembling the entire mixing device.

[0041] See also Figures 1 to 4 As shown, in one embodiment of the present invention, the first connecting member is threadedly connected to the second interface 14 , and the second connecting member 30 is threadedly connected to the first interface 13 .

[0042] In this embodiment, the inner wall surfaces of the first interface 13 and the second interface 14 are both provided with threads, and the outer wall surfaces of the first connecting member and the second connecting member 30 are both provided with threads to realize the connection between the first connecting member and the second interface 14, and the connection between the second connecting member 30 and the first interface 13.

[0043] See also Figures 1 to 4As shown, in one embodiment of the utility model, the mixing device also includes a first seal and a second seal 40, the first seal is arranged corresponding to the liquid inlet pipe, the first seal is sleeved on the liquid inlet pipe, the first seal is located between the first connecting member and the liquid inlet channel 12, the first seal is sealed and connected to the liquid inlet pipe, the first connecting member presses the first seal so that the end of the first seal facing away from the first connecting member forms a sealing fit with the bottom of the second interface 14, the second seal 40 is sleeved on the liquid outlet pipe 20, the second seal 40 is located between the second connecting member 30 and the liquid outlet channel 11, the second seal 40 is sealed and connected to the liquid outlet pipe 20, the second connecting member 30 presses the second seal 40 so that the end of the second seal 40 facing away from the second connecting member 30 forms a sealing fit with the bottom of the first interface 13.

[0044] In this embodiment, the provision of the first seal and the second seal 40 can ensure the sealing between the liquid outlet channel 11 and the liquid outlet pipe 20, and the sealing between the liquid inlet pipe and the liquid inlet channel 12, thereby preventing liquid from leaking from the mixing body 10 during transportation, and avoiding material waste and environmental risks caused by leakage.

[0045] In one embodiment, the mixing body 10 , the liquid inlet pipe and the liquid outlet pipe 20 may be made of any one of polyetheretherketone (PEEK), stainless steel, titanium metal, and dimethylsiloxane (PDMS).

[0046] It should be noted that the inner diameters of the liquid inlet pipe and the liquid outlet pipe 20 can be set according to actual production needs.

[0047] See also Figures 1 to 4 As shown, in one embodiment of the present invention, the first seal and the second seal 40 are both conical structures, the small diameter end of the first seal faces the first connecting member, and the small diameter end of the second seal 40 faces the second connecting member 30 .

[0048] Through the above arrangement, a good sealing effect can be maintained under different pressures, effectively preventing liquid leakage.

[0049] See also Figures 1 to 4 As shown, in one embodiment of the present invention, the inner wall of the liquid outlet channel 11 is provided with a hydrophilic coating, and the inner wall of the liquid inlet channel 12 is provided with a hydrophobic coating.

[0050] In this embodiment, the hydrophilic coating can prevent the liposomes from adhering to the inner wall of the liquid outlet channel 11, thereby reducing material loss and improving the recovery rate and purity of the liposome preparation. The hydrophobic coating can prevent the organic phase solution (such as ethanol solution) from interacting with the inner wall of the liquid inlet channel 12, reducing nonspecific adsorption.

[0051] In one embodiment, the hydrophilic coating may be made of polyvinyl alcohol (PVA) or polyethylene glycol (PEG), and the hydrophobic coating may be made of polydimethylsiloxane (PDMS).

[0052] See also Figures 1 to 4 As shown, in one embodiment of the utility model, the mixing body 10 includes a mixing part 15 and a connecting part 16, the liquid outlet channel 11 and the liquid inlet structure are both arranged on the mixing part 15, the mixing part 15 is connected to the connecting part 16, and along the first direction, the connecting part 16 has a first end and a second end arranged opposite to each other, and the first end and the second end are both provided with at least one connecting hole 17.

[0053] In this embodiment, the first direction refers to the length extension direction of the connection portion 16. The arrangement of the connection hole 17 enables the mixing body 10 to be connected to other devices (such as a temperature control system).

[0054] In one embodiment, the mixing device further includes a temperature control system for adjusting the temperature of the solution in the liquid inlet channel 12 and the liquid outlet channel 11 to ensure the optimal phase change conditions required in the liposome preparation process. The temperature control system can adopt the temperature control equipment of the prior art, and the specific structure is not repeated here.

[0055] It should be noted that the mixing device of the present application can be used in conjunction with purification equipment (such as a tangential flow filtration system) and an online detection device, and the online detection device is used to detect lipid concentration and liposome particle size.

[0056] Example 1

[0057] Using the mixing device of the present application, amikacin liposomes of different particle sizes are prepared by changing the total flow rate. A certain amount of dipalmitoylphosphatidylcholine (DPPC) and cholesterol are added to anhydrous ethanol, and each component is completely dissolved by ultrasound and used as an organic phase solution, wherein the concentration of dipalmitoylphosphatidylcholine is 12 mg / mL and the concentration of cholesterol is 8 mg / mL. A certain amount of amikacin sulfate is added to redistilled water, and after being completely dissolved by ultrasound, it is used as an aqueous phase solution, wherein the concentration of amikacin sulfate is 40 mg / mL and the pH is 6.4. The above-mentioned organic phase solution and aqueous phase solution are respectively passed into two liquid inlet channels for mixing, and then continuously online filtration is performed through a continuous tangential flow filtration system to remove ethanol and free drugs in the crude liposome to obtain amikacin liposomes, and then the particle size of the liposome sample is detected and analyzed, and the test results are shown in Table 1. Among them, the total flow rate refers to the sum of the flow rates of the two liquid inlet pipes.

[0058] Table 1

[0059]

[0060] Example 2

[0061] Using the mixing device of the present application, amikacin liposomes of different particle sizes are prepared by changing the flow rate ratio. A certain amount of dipalmitoylphosphatidylcholine (DPPC) and cholesterol are added to anhydrous ethanol, and each component is completely dissolved by ultrasound and used as an organic phase solution, wherein the concentration of dipalmitoylphosphatidylcholine is 18 mg / mL and the concentration of cholesterol is 12 mg / mL. A certain amount of amikacin sulfate is added to redistilled water, and after being completely dissolved by ultrasound, it is used as an aqueous phase solution, wherein the concentration of amikacin sulfate is 40 mg / mL and the pH is 6.4. The above-mentioned organic phase solution and aqueous phase solution are respectively passed into two liquid inlet channels for mixing, and then continuously filtered online by a continuous tangential flow filtration system to remove ethanol and free drugs in the crude liposomes to obtain amikacin liposomes, and then the particle size of the liposome sample is detected and analyzed. The test results are shown in Table 2.

[0062] Table 2

[0063]

[0064] Example 3

[0065] Using the mixing device of the present application, amikacin liposomes of different particle sizes are prepared by changing the concentration ratio of phospholipids / cholesterol. A certain amount of soybean phosphatidylcholine (SPC) and cholesterol are added to anhydrous ethanol, and each component is completely dissolved by ultrasound and used as an organic phase solution, wherein, in prescription one, the concentration of soybean phosphatidylcholine is 18 mg / mL, and the concentration of cholesterol is 6 mg / mL; in prescription two, the concentration of soybean phosphatidylcholine is 20 mg / mL, and the concentration of cholesterol is 4 mg / mL. A certain amount of amikacin sulfate is added to redistilled water, and after being completely dissolved by ultrasound, it is used as an aqueous phase solution, wherein the concentration of amikacin sulfate is 40 mg / mL and the pH is 6.4. The above-mentioned organic phase solution and aqueous phase solution are respectively passed into two liquid inlet channels for mixing, and the obtained crude liposome is dialyzed to remove free amikacin sulfate and ethanol, and the liposome particle size and the recovery rate of amikacin are measured. The test results are shown in Table 3.

[0066] Table 3

[0067]

[0068] Example 4

[0069] Using the mixing device of the present application, amikacin liposomes of different particle sizes are prepared by changing phospholipids. A certain amount of soybean lecithin and cholesterol are weighed and added to anhydrous ethanol, and each component is dissolved by ultrasound and used as organic phase solvent A. A certain amount of hydrogenated soybean lecithin and cholesterol are weighed and added to anhydrous ethanol, and each component is dissolved by ultrasound and used as organic phase solvent B, wherein the phospholipid concentration and cholesterol concentration are kept consistent (phospholipid concentration is 30 mg / mL, and cholesterol concentration is 10.15 mg / ml); dexamethasone with the same mass concentration of 5.2 mg / mL is added to organic phase solvent A and organic phase solvent B, respectively, and the above organic phase solution and pH7.4 phosphate buffer (PBS, Phosphate Buffered Saline aqueous phase solution) are respectively passed into two liquid inlet channels for mixing. Amikacin liposomes are obtained, and then the distribution of liposome particle size is measured, and the test results are shown in Table 4.

[0070] Table 4

[0071]

[0072] From the above description, it can be seen that the above-mentioned embodiments of the utility model achieve the following technical effects: a liquid outlet channel and a liquid inlet structure are provided, the liquid inlet structure includes two liquid inlet channels arranged at a preset angle, the liquid outlet ends of the two liquid inlet channels intersect and are connected, and the liquid outlet channel is connected to the intersection of the two liquid inlet channels. Through the above-mentioned arrangement, the contact area between the fluids can be increased, the molecular diffusion process can be accelerated, and sufficient turbulence can be generated at the intersection of the fluids, thereby promoting local mixing, thereby improving the mixing efficiency, and realizing orderly and efficient mixing of the aqueous phase and the ethanol phase solution at the intersection.

[0073] Obviously, the embodiments described above are only some embodiments of the utility model, not all embodiments. Based on the embodiments of the utility model, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the utility model.

[0074] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0075] The above description is only the preferred embodiment of the utility model, and is not intended to limit the utility model. For those skilled in the art, the utility model can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the utility model shall be included in the protection scope of the utility model.

Claims

1. A mixing device, characterized in that: include: A mixing body (10) comprises a liquid outlet channel (11) and a liquid inlet structure, wherein the liquid inlet structure comprises two liquid inlet channels (12) arranged at a preset angle, the liquid outlet channel (11) is located between the two liquid inlet channels (12), the liquid outlet ends of the two liquid inlet channels (12) intersect and communicate with each other, and the liquid outlet channel (11) is connected to the intersection of the two liquid inlet channels (12).

2. The mixing device according to claim 1, characterized in that The angle between the liquid inlet channel (12) and the liquid outlet channel (11) is α, and the value range of α is 30° to 75°; and / or the two liquid inlet channels (12) are axially symmetrically arranged about the central axis of the liquid outlet channel (11).

3. The mixing device according to claim 1, characterized in that The mixing body (10) further comprises a first interface (13) and a second interface (14); the liquid outlet channel (11) is connected to one of the first interfaces (13), and each of the liquid inlet channels (12) is connected to one of the second interfaces (14).

4. The mixing device according to claim 3, characterized in that The mixing device further comprises a liquid inlet pipe, a liquid outlet pipe (20), a first connecting piece and a second connecting piece (30); the liquid inlet pipe is in communication with the liquid inlet channel (12); the first connecting piece is arranged corresponding to the liquid inlet pipe; the liquid inlet pipe is connected to the second interface (14) via the first connecting piece; the liquid outlet pipe (20) is in communication with the liquid outlet channel (11); the second connecting piece (30) is arranged corresponding to the liquid outlet pipe (20); and the liquid outlet pipe (20) is connected to the first interface (13) via the second connecting piece (30).

5. The mixing device according to claim 4, characterized in that The first connecting piece is sleeved on the liquid inlet pipe and fixedly connected to the liquid inlet pipe, both ends of the liquid inlet pipe protrude from the first connecting piece, and one end of the liquid inlet pipe located in the second interface (14) extends into the liquid inlet channel (12). The second connecting piece (30) is sleeved on the liquid outlet pipe (20) and fixedly connected to the liquid outlet pipe (20), both ends of the liquid outlet pipe (20) protrude from the second connecting piece (30), and one end of the liquid outlet pipe (20) located in the first interface (13) extends into the liquid outlet channel (11).

6. The mixing device according to claim 4, characterized in that The first connecting piece is threadedly connected to the second interface (14), and the second connecting piece (30) is threadedly connected to the first interface (13).

7. The mixing device according to claim 4, characterized in that The mixing device further comprises a first sealing member and a second sealing member (40), wherein the first sealing member is arranged corresponding to the liquid inlet pipe, the first sealing member is sleeved on the liquid inlet pipe, the first sealing member is located between the first connecting member and the liquid inlet channel (12), the first sealing member is sealingly connected to the liquid inlet pipe, the first connecting member presses the first sealing member so that an end of the first sealing member facing away from the first connecting member forms a sealing fit with the bottom of the second interface (14), the second sealing member (40) is sleeved on the liquid outlet pipe (20), the second sealing member (40) is located between the second connecting member (30) and the liquid outlet channel (11), the second sealing member (40) is sealingly connected to the liquid outlet pipe (20), the second connecting member (30) presses the second sealing member (40) so that an end of the second sealing member (40) facing away from the second connecting member (30) forms a sealing fit with the bottom of the first interface (13).

8. The mixing device according to claim 7, characterized in that The first sealing member and the second sealing member (40) are both conical structures, the small diameter end of the first sealing member faces the first connecting member, and the small diameter end of the second sealing member (40) faces the second connecting member (30).

9. The mixing device according to any one of claims 1 to 3, characterized in that The inner wall of the liquid outlet channel (11) is provided with a hydrophilic coating, and the inner wall of the liquid inlet channel (12) is provided with a hydrophobic coating.

10. The mixing device according to any one of claims 1 to 3, characterized in that The mixing body (10) comprises a mixing portion (15) and a connecting portion (16); the liquid outlet channel (11) and the liquid inlet structure are both arranged on the mixing portion (15); the mixing portion (15) is connected to the connecting portion (16); along a first direction, the connecting portion (16) has a first end and a second end that are arranged opposite to each other; the first end and the second end are both provided with at least one connecting hole (17).