Enclosed liposoluble nutrient liposome preparation device and method

Abstract

The application discloses a closed liposoluble nutrient liposome preparation device and method. The device comprises a homogenizing device and a circulating primary emulsification device connected with an inlet of the homogenizing device. The circulating primary emulsification device comprises an oil phase stirring ingredient tank and a water phase stirring ingredient tank connected through pipelines. The oil phase stirring ingredient tank and the water phase stirring ingredient tank are further connected with a vacuum pump and a compressed air device. Rotating pumps for pumping materials are arranged at outlets of the oil phase stirring ingredient tank and the water phase stirring ingredient tank. The circulating primary emulsification device arranged in front of the homogenizing device shortens the hydration time, and can obtain a circulating primary emulsion with a smaller particle size, thereby providing favorable conditions for homogenization of the liposome.

Description

Technical Field

[0001] This invention relates to the field of liposome preparation technology, and in particular to a closed-type apparatus and method for preparing fat-soluble nutrient liposomes. Background Technology

[0002] Fat-soluble nutrients include vitamins A, D, E, and K, lutein, lycopene, beta-carotene, astaxanthin, coenzyme Q10, lutein, zeaxanthin, DHA, EPA, and so on. These fat-soluble nutrients share common characteristics: they contain double bonds or phenolic hydroxyl groups, are easily oxidized by light and oxygen, and lose their physiological activity; they have low absorption and metabolic rates and low bioavailability; and they are insoluble in water. In practical applications, they are mainly used in microencapsulated powder form, and tend to separate into layers in liquid foods.

[0003] Liposomes are bilayer vesicles composed of lipid molecules. Each layer is a lipid bilayer, and the spaces between the layers and the core are aqueous phases. They have a biomembrane-like structure and are characterized by good biocompatibility, low toxicity, sustained release, and targeting.

[0004] Currently, there are various methods for preparing liposomes, and different fields primarily employ different methods. In the cosmetics field, liposomes are often prepared using repeated freeze-thaw cycles and solvent injection methods. The disadvantages of these methods include low automation, long production cycles, low encapsulation efficiency, and a tendency for solvent residue. In the pharmaceutical field, liposomes are mostly prepared using extrusion methods. Laboratory extrusion typically uses high-pressure gas as the extrusion power source, generally not exceeding 60 Bar. Production requires high-pressure power pumps, with maximum pressures ranging from 300 Bar to 500 Bar. The disadvantages of these methods include high equipment investment and high costs for key consumables such as polycarbonate membranes. Liposomes used in food applications require solvent safety and no residue, a certain level of production efficiency, and good cost control. Furthermore, the easily oxidized nature of fat-soluble vitamins necessitates less exposure or processing time. Existing food liposome preparation processes generally suffer from long hydration times, high equipment investment, high pressure requirements for homogenization equipment (typically greater than 1000 Bar), low homogenization efficiency, large liposome particle size after homogenization, uneven liposome distribution, and easy oxidation of nutrients during preparation. Therefore, these problems limit the application and development of fat-soluble nutrient liposomes in food. Summary of the Invention

[0005] According to one embodiment of the present invention, the objective is to provide a closed-loop apparatus and method for preparing liposomes of fat-soluble nutrients, thereby solving at least one of the aforementioned problems existing in current liposome preparation processes. This objective can be achieved through the following technical solutions:

[0006] According to one aspect of the present invention, a closed-loop liposome preparation apparatus for fat-soluble nutrients is provided, comprising a homogenizing device and a circulating primary emulsifier connected to its inlet.

[0007] The circulating primary emulsification device includes: an oil phase mixing and batching tank and a first threaded conveying pipe connected to its outlet; an aqueous phase mixing and batching tank and a second threaded conveying pipe connected to its outlet; a third circulation pipe; a fourth circulation pipe; and a fifth circulation pipe. The first and second threaded conveying pipes are connected to each other via a four-way valve. The third port of the four-way valve is connected to one end of the third circulation pipe via a connecting pipe, and the fourth port of the four-way valve is connected to the homogenizing equipment. The inner wall of the connecting pipe narrows inward in the middle to form an annular boss, and a second channel is formed in the middle of the annular boss.

[0008] The other end of the third circulation pipe is connected to the fourth and fifth circulation pipes respectively via a three-way valve. The fourth circulation pipe is connected to the oil phase mixing and batching tank, and the fifth circulation pipe is connected to the water phase mixing and batching tank. The oil phase mixing and batching tank and the water phase mixing and batching tank are also connected to a vacuum pump and a compressed air device. The outlets of the oil phase mixing and batching tank and the water phase mixing and batching tank are equipped with rotor pumps for pumping materials.

[0009] Optionally, the connecting pipe is further provided with a coaxial base, which is located on the side where the annular boss is connected to the third circulation pipe, and forms a gap with the end face of the annular boss on the same side. The outer periphery of the base forms a third channel with the inner wall of the connecting pipe.

[0010] Optionally, the base is adjustablely mounted on the connecting pipe, and its position along the axial direction of the connecting pipe is adjustable, so that the size of the gap is adjustable to regulate the pressure inside the connecting pipe.

[0011] Optionally, the base is adjustable and can be mounted on the connecting pipe using an adjustable mounting structure.

[0012] Furthermore, the adjustable mounting structure includes: a connecting shaft, a gear meshing transmission mechanism, and a seal; an adjustment hole is opened on the wall of the connecting pipe; the connecting shaft passes through the adjustment hole, one end is connected to the base inside the connecting pipe, and the other end is connected to the gear meshing transmission mechanism fixedly installed on the outer wall of the connecting pipe. The gear meshing transmission mechanism is used to drive the connecting shaft to move within the adjustment hole, thereby realizing the adjustable position of the base within the connecting pipe along the axial direction of the connecting pipe; the seal is provided at the adjustment hole and is used to seal the adjustment hole after the gap size is determined.

[0013] Optionally, the gear meshing transmission mechanism includes: a gear, a first rack, and a fixing member; wherein, the gear is connected to the other end of the connecting shaft; the first rack is fixed on the outer wall of the connecting pipe and meshes with the gear; a screwing member is fixed on the gear for adjusting the meshing position of the gear and the first rack; the fixing member is used to fix the gear after the meshing position of the gear and the first rack is determined.

[0014] Optionally, the fixing member is a second rack, which is fixed to the connecting pipe and the distance between the second rack and the gear is adjustable. The second rack fixes the gear by moving to mesh with the gear.

[0015] Optionally, the second rack is mounted on the first rack via a movable connector, parallel to the first rack with an adjustable distance between them, and located on opposite sides of the gear. When the position of the base within the connecting tube needs adjustment, the second rack is positioned away from the gear. Once the base's position within the connecting tube is determined, the second rack moves to engage with the gear, thereby securing the gear.

[0016] Optionally, the movable connector is a fixed strip with a groove and a nut that cooperates with it, and the two sets of movable connectors form an adjustable rectangular structure with the first rack and the second rack.

[0017] Optionally, the fixing component is a second rack, which is installed on the first rack, parallel to the first rack, and the distance between the two is adjustable. The second rack and the first rack are located on both sides of the gear. When it is necessary to adjust the position of the base in the connecting tube, the second rack is located away from the gear. After the position of the base in the connecting tube is determined, the second rack moves to mesh with the gear, thereby fixing the gear.

[0018] Optionally, the adjustable range of the gap is 5mm to 15mm, and a pressure gauge is installed at the connecting pipe to detect the pressure inside the connecting pipe. Further, a pressure gauge is installed at the gap inside the connecting pipe to detect the pressure at the gap.

[0019] Optionally, the oil phase mixing tank and the water phase mixing tank are arranged horizontally and symmetrically distributed on both sides of the third circulation pipe.

[0020] Optionally, the first threaded conveying pipe and the second threaded conveying pipe have the same structure. They are provided with 2 to 8 spirals, with a spiral depth of 1 mm to 3 mm, a spiral width of 5 mm to 20 mm, and a pipe diameter * π: pitch = 0.4 to 2.80.

[0021] Optionally, the end faces on both sides of the annular boss are chamfered.

[0022] Optionally, the annular boss has a chamfer of 30° to 60° on the end face connected to the third interface of the four-way valve, and a chamfer of 30° to 45° on the end face connected to the third circulation pipe.

[0023] Optionally, the base is a cylinder with a diameter greater than the diameter of the second channel formed inside the annular boss and smaller than the inner diameter of the connecting pipe.

[0024] Optionally, the diameter of the second channel formed within the annular boss is 30mm to 50mm. The diameter of the base is 35mm to 55mm.

[0025] Optionally, the length of the annular boss is 100mm to 200mm. The length of the base is 80mm to 180mm. The length of the connecting pipe on the side where the annular boss connects to the third interface of the four-way valve is 100mm to 150mm.

[0026] According to another aspect of the present invention, a closed-loop method for preparing liposomes of fat-soluble nutrients is provided, which uses the closed-loop liposome preparation apparatus, comprising: adding oil phase material to an oil phase stirring and mixing tank, evacuating the tank using a vacuum pump, heating and stirring; adding aqueous phase material to an aqueous phase stirring and mixing tank, heating and stirring; turning on a rotor pump and a compressed air device to pump the material, the oil phase material and the aqueous phase material are accelerated through a first threaded conveying pipe and a second threaded conveying pipe respectively, and then flushed and hydrated at a four-way valve, accelerated through a second channel between a connecting pipe and its inner annular boss, and sprayed from the gap and a third channel into a third circulation pipe, circulating and hydrated in a circulation pipeline formed by the third circulation pipe, the oil phase stirring and mixing tank and the first threaded conveying pipe and the connecting pipe or in a circulation pipeline formed by the third circulation pipe, the aqueous phase stirring and mixing tank and the second threaded conveying pipe and the connecting pipe, to obtain a circulating primary emulsion; opening the fourth port of the four-way valve, the circulating primary emulsion enters a homogenizing device for homogenization to form liposomes.

[0027] Optionally, the method further includes: adjusting the axial position of the base within the connecting pipe to determine the gap size; adjusting the rotational speed of the rotor pump and / or the flow rate of the compressed air equipment to adjust the pressure generated within the connecting pipe. Further optionally, the rotational speed of the rotor pump is adjusted to provide a material flow rate of 0.1 m / s to 2.5 m / s. Further optionally, the pressure generated at the gap within the connecting pipe is adjusted to 10 Bar to 30 Bar.

[0028] Optionally, the step of determining the gap size by adjusting the position of the base in the axial direction within the connecting pipe includes: adjusting the gear meshing transmission mechanism to drive the connecting shaft to move within the adjusting hole, thereby adjusting the position of the base in the axial direction within the connecting pipe and determining the gap size; after determining the gap size, fixing the gear by the fixing component in the gear meshing transmission structure and sealing the adjusting hole with a sealing component.

[0029] Optionally, the step of speeding up the material flow after passing through the first and second threaded conveying pipes refers to increasing the material flow rate by at least 3.5%.

[0030] Optionally, during hydration, the circulation time is 5 min to 20 min.

[0031] Optionally, the initial emulsion after cycling has a particle size of 250 nm to 500 nm and a Span coefficient of 1.0 to 6.0.

[0032] Optionally, during homogenization, the homogenization pressure is 400 Bar to 1000 Bar; the number of homogenization cycles is 1 to 3.

[0033] Optionally, the liposomes have a particle size of 105 nm to 155 nm and a Span coefficient of 0.800 to 1.325.

[0034] Optionally, the single batch or the last batch can be circulated in the oil phase stirring and batching tank, which can greatly reduce material loss. Here, circulating in the oil phase stirring and batching tank refers to circulating hydration in the circulation pipeline formed by the third circulation pipe, the oil phase stirring and batching tank, and the first threaded conveying pipe and connecting pipe.

[0035] Beneficial effects: According to one embodiment of the present invention, a circulating primary emulsification device is set before the homogenizing equipment. By equipping the oil phase mixing tank and the water phase mixing tank with a vacuum pump, a rotor pump and compressed air equipment, and connecting the oil phase mixing tank and the water phase mixing tank with two spiral conveying pipes in a relative connection manner, the oil phase material and the water phase material are accelerated by the first spiral conveying pipe and the second spiral conveying pipe respectively, and then flushed and combined at the four-way valve. After passing through the connecting pipe, they enter the circulation pipeline for circulating hydration. This results in a circulating primary emulsion with a smaller particle size and high uniformity, shortens the hydration time, provides favorable conditions for homogenization in the homogenizing equipment, and enables the homogenizing equipment to prepare liposomes of the required particle size under a lower homogenization pressure, reducing the wear and tear of the homogenizing equipment and extending its service life.

[0036] Compared with the prior art, some embodiments in this application also have the following advantages:

[0037] 1) Circulating hydration is carried out in a circulation pipeline formed by an oil-phase stirring and mixing tank or an aqueous-phase stirring and mixing tank and circulation pipes (the third, fourth, and fifth circulation pipes). It can be flexibly used by adjusting four-way valves and / or three-way valves, eliminating the need for a separate circulating emulsification tank, thus reducing equipment investment and minimizing losses caused by material transfer. It is suitable for pilot-scale to large-scale production of liposomes for fat-soluble nutrients. Furthermore, due to the higher cost of the oil phase, single-batch or the final batch can be circulated within the oil-phase stirring and mixing tank, significantly reducing material loss.

[0038] 2) When circulating hydration is carried out in the circulation pipeline consisting of the aqueous phase stirring and batching tank and the circulation pipe, the next batch of materials can be prepared in the oil phase stirring and batching tank, thereby saving production time; when circulating hydration is carried out in the circulation pipeline consisting of the oil phase stirring and batching tank and the circulation pipe, high viscosity and high added value oil phase residue can be carried into the circulation, thereby improving the yield and saving costs.

[0039] 3) The fat-soluble nutrient liposome preparation device of this application is closed and equipped with a vacuum pump, which avoids the oxidation of materials and improves the stability and quality of fat-soluble nutrient liposomes. Attached Figure Description

[0040] Figure 1 This is a schematic diagram of a closed-type fat-soluble nutrient liposome preparation device according to an embodiment of the present invention;

[0041] Figure 2 This is a schematic cross-sectional view of the connecting pipe in one embodiment of the present invention;

[0042] Figure 3 This is a schematic diagram of the mounting structure of the base in one embodiment of the present invention;

[0043] Figure 4 This is a top view of the connecting pipe in one embodiment of the present invention;

[0044] Figure 5 This is a schematic diagram of the gear meshing transmission structure in one embodiment of the present invention;

[0045] Figure 6 This is a particle size distribution diagram of the primary emulsion after circulation obtained in Example 1 of the present invention;

[0046] Figure 7 This is a particle size distribution diagram of the liposomes obtained in Example 1 of the present invention;

[0047] Figure 8 This is a particle size distribution diagram of the liposomes obtained in Comparative Example 1 of the present invention.

[0048] Reference numerals: Circulating primary emulsifier 100, homogenizer 200, oil phase mixing and batching tank 1, first threaded conveying pipe 11, first rotor pump 12, aqueous phase mixing and batching tank 2, second threaded conveying pipe 21, second rotor pump 22, third circulation pipe 3, fourth circulation pipe 4, fifth circulation pipe 5, four-way valve 6, three-way valve 7, vacuum pump 8, compressed air equipment 9, valves at the connection between the three-way valve and the fourth and fifth circulation pipes are 41 and 51 respectively, valves at the connection between the four-way valve and the first threaded conveying pipe, second threaded conveying pipe, third circulation pipe, and homogenizer are 61, 62, 63, and 64 respectively, connecting pipe 31, pressure gauge 315, base 311, connecting shaft 312, gear meshing transmission mechanism 313, seal 314, metal gasket 316, gear 3131, first rack 3132, second rack 3133, fixing strip 3134. Detailed Implementation

[0049] The technical solution of the present invention will be clearly and completely described below with reference to embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the present invention or its application or use. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0050] Figure 1 This illustration schematically depicts a closed-loop liposome preparation apparatus for fat-soluble nutrients provided in one embodiment of this application. The apparatus includes a homogenizer 200 and a circulating primary emulsifier 100 connected to its inlet; the circulating primary emulsifier 100 includes an oil phase mixing tank 1 and an aqueous phase mixing tank 2 connected via pipelines.

[0051] The outlet of the oil phase mixing and batching tank 1 is connected to the first threaded conveying pipe 11, and the outlet of the aqueous phase mixing and batching tank 2 is connected to the second threaded conveying pipe 21. The two threaded conveying pipes are arranged horizontally and connected to each other through two opposite ports of the four-way valve 6. Rotary pumps for pumping materials are installed on the pipes connecting the outlets of the two threaded conveying pipes and the two batching tanks, namely the first rotor pump 12 and the second rotor pump 22. The third port above the four-way valve 6 is connected to one end of the third circulation pipe 3, and the other end of the third circulation pipe 3 is connected to the fourth circulation pipe 4 and the fifth circulation pipe 5 through the three-way valve 7. The fourth circulation pipe 4 is connected to the oil phase mixing and batching tank 1, and the fifth circulation pipe 5 is connected to the aqueous phase mixing and batching tank 2. The fourth port below the four-way valve 6 is connected to the inlet of the homogenizing equipment 200. The third circulation pipe, the oil phase mixing and batching tank, the first threaded conveying pipe and the connecting pipe can form a circulation pipeline, and the third circulation pipe, the aqueous phase mixing and batching tank, the second threaded conveying pipe and the connecting pipe can form a circulation pipeline. The circulating primary emulsifier 100 is a closed system, and the upper part of the two mixing tanks is connected to a vacuum pump 8, which can reduce oxidation and remove solvents when preparing the oil phase. In addition, the upper part of the two mixing tanks is also connected to a compressed air device 9, which can provide power during circulation by introducing compressed air into the mixing tanks.

[0052] Furthermore, preferably, the two mixing tanks can be arranged horizontally and at the same height to improve the material flushing hydration efficiency and the circulating hydration efficiency. For example... Figure 1As shown, the third circulation pipe 3 is arranged vertically, and the two batching tanks are symmetrically distributed relative to the third circulation pipe 3. Specifically, the oil phase stirring batching tank, the first threaded conveying pipe, and the fourth circulation pipe, along with the water phase stirring batching tank, the second threaded conveying pipe, and the fifth circulation pipe, are symmetrically distributed on both sides of the third circulation pipe, providing favorable conditions for material counter-hydration and enabling the material to obtain greater counter-hydration energy.

[0053] In this application, the materials from the outlets of the two batching tanks are conveyed via two threaded conveying pipes, connected in a relative manner by a four-way valve. The aqueous and oil phases form rapid turbulence within the threaded conveying pipes, significantly increasing the material flow rate (compared to straight pipe conveying) by at least 3.5%. This increases the energy for the oil and aqueous phases to flush each other, which is beneficial for obtaining a primary emulsion with smaller particle sizes. Furthermore, in this application, the oil and aqueous phases are directly conveyed through the threaded conveying pipes for flushing and hydration after exiting the tanks, rather than flushing the mixed material. This avoids water entering the oil phase batching tank, saving cleaning or preparation time and further shortening the hydration time. Optionally, the two threaded conveying pipes have identical structures, each configured with 2–8 spirals inside, a spiral depth of 1–3 mm, and a spiral width of 5 mm–20 mm. Further, the pipe diameter * π: pitch = 0.4–2.80 (determined by the number of spirals and the tangent angle). By using the aforementioned threaded conveying pipe, the frictional resistance between the material and the pipe can be effectively reduced, the mechanical losses caused by turbulence in the pipeline can be reduced, and a stable radial flow rate can be formed.

[0054] In addition, to test the speed-up effect of the spiral conveyor, the inventors conducted a comparative experiment on the flow velocities obtained after conveying materials using a spiral conveyor and a regular straight pipe. The comparison results are shown in Table 1 below. Flow meters were installed at the inlet and outlet of the spiral conveyor (or regular straight pipe). The flow velocity of the material after being conveyed through the pipeline is calculated using the formula: V=4×Q÷(π×d) 2 The calculation is performed using the following formula: V is the flow velocity, Q is the flow meter reading, and d is the inner diameter of a standard straight pipe or spiral conveying pipe.

[0055] Table 1 Material Flow Rate After Conveying Through Spiral Conveyor Pipes and Ordinary Straight Pipes (Table 1)

[0056] Rotary pump speed (r / min) 800 900 1000 Spiral conveyor pipe - Flow velocity (m / s) 1.56 1.85 2.06 Standard straight pipe - flow velocity (m / s) 1.50 1.76 1.94

[0057] As can be seen from the comparison in Table 1, the use of threaded conveying pipes significantly increases the material flow rate, up to approximately 6%, which greatly increases the energy during the collision of oil and water phase liquids.

[0058] In a preferred embodiment, the third interface above the four-way valve 6 is connected to one end of the third circulation pipe 3 through a connecting pipe 31. Furthermore, the middle part of the inner wall of the connecting pipe 31 is narrowed inward to form an annular boss, and the middle of the annular boss forms a narrowed channel, i.e., a second channel, for material to pass through.

[0059] After the material is accelerated through the two threaded conveying pipes, it is hydrated at high speed at the four-way valve 6 and sprayed out from the third port above the four-way valve 6. The energy is accumulated in the second channel narrowed by the annular boss, which can generate a pressure of about 1 bar to 4 bar in the pipe, such as 1 bar, 2 bar, 3 bar, 4 bar. After passing through the narrowed channel, the energy is released instantly and sprayed into the third circulation pipe 3, and then circulated and hydrated to obtain a better post-circulation primary emulsion and shorten the hydration time.

[0060] Optionally, the specific dimensions of the connecting pipe structure are as follows: the inner diameter of the connecting pipe 31 can be 20mm to 30mm, the diameter of the narrowed second channel of the annular boss is set to 30mm to 50mm, and the length is 100mm to 200mm; the connecting pipe with these dimensions allows the emulsion to accumulate higher energy after flushing and hydration; in addition, setting the length of the connecting pipe below the annular boss to 100mm to 150mm, after flushing and hydration, the emulsion first passes through this section of the connecting pipe 31 before entering the narrowed second channel, which can better utilize the function of the second channel.

[0061] In addition, such as Figure 2 As shown, to maximize the function of the narrowing channel, a chamfer is provided on the end face of the annular boss connected to the third interface of the four-way valve 6, i.e., below the annular boss. The chamfer angle range is set to 30° to 60°, allowing all the flushing fluid to smoothly enter the narrowing channel. Furthermore, a chamfer is also provided on the other end face of the annular boss, i.e., above the annular boss. The chamfer angle here is preferably set to 30° to 45° to release high energy instantly. It should be noted that in the embodiment where the base 311 is provided, this chamfer should not be too large, as a large chamfer angle will hinder the effective utilization of the gap effect. In addition, providing a chamfer structure to the annular boss can extend the service life of the connecting pipe.

[0062] In addition, such as Figure 2 As shown, a pressure gauge 315 is also installed at the connecting pipe 311 to detect the pressure inside the connecting pipe. Furthermore, the pressure gauge 315 is used to detect the pressure at the gap.

[0063] In a preferred embodiment, a base 311 is further provided inside the connecting pipe 31. The base 311 has a gap with the end face of the annular boss, and the outer periphery of the base forms a third channel with the inner wall of the connecting pipe. After the material passes through the second channel with its inner diameter narrowed, it then passes through the gap and the third channel before entering the third circulation pipe.

[0064] like Figure 2 and 3As shown, a base 311 is installed in the connecting pipe 31 on one side of the annular boss connected to the third circulation pipe 3. The base is coaxial with the connecting pipe, and a gap is formed between the bottom surface of the base and the upper end face of the annular boss. The outer periphery of the base and the inner wall of the connecting pipe form a third channel.

[0065] The material accumulates energy and accelerates rapidly in the second channel with a narrower inner diameter, while simultaneously releasing its energy at high speed through the gap, generating a pressure of approximately 10 Bar to 30 Bar, such as 10 Bar, 12 Bar, 15 Bar, 20 Bar, 25 Bar, and 30 Bar. It is then sprayed into the third circulation pipe 3 through the third channel, generating a pressure of approximately 1 Bar to 10 Bar, such as 1 Bar, 3 Bar, 5 Bar, 8 Bar, and 10 Bar. Throughout the process, the material undergoes multiple accelerations, energy accumulation and releases, impacts, shearing, and cavitation effects. After circulating and hydrating for 5 to 20 minutes, a highly uniform primary emulsion with a small particle size can be obtained, significantly improving hydration efficiency, shortening hydration time, and facilitating homogenization in the homogenizing equipment.

[0066] Optionally, the base structure dimensions are as follows: The base is designed as a cylindrical structure. Compared to a polygonal cylindrical structure, the absence of sharp edges in a cylinder results in a more uniform initial emulsion. The diameter of the base 311 is larger than the diameter of the narrowing channel of the annular boss but smaller than the diameter of the connecting pipe 31. For example, based on a narrowing channel diameter of 30mm to 50mm, the diameter of the base 311 is set to 35mm to 55mm, and the width of the annular third channel formed by the base 311 and the inner wall of the connecting pipe is 20mm to 30mm. The length of the base 311 can be set to 80mm to 180mm, and the length of the connecting pipe 31 on the side where the annular boss connects to the third circulation pipe 3 is longer than the base 311, for example, it can be 350mm to 400mm. Using the base structure with the above dimensions in conjunction with the connecting pipe and its annular platform can achieve a better initial emulsification effect.

[0067] In a preferred embodiment, the base is adjustablely mounted on the connecting tube, and its position along the axial direction of the connecting tube is adjustable, so that the size of the gap can be adjusted, the pressure inside the connecting tube can be adjusted, and the preparation requirements of liposomes with different particle sizes can also be met.

[0068] The base can be mounted on the connecting pipe via an adjustable mounting structure, allowing the base to be adjusted vertically within the connecting pipe. For example... Figure 3 and Figure 4As shown, the adjustable mounting structure includes: a connecting shaft 312, a gear meshing transmission mechanism 313, and a seal 314. An adjustment hole is formed in the wall of the connecting pipe; the connecting shaft 312 passes through the adjustment hole, with one end connected to a base 311 inside the connecting pipe 31, and the other end connected to the gear meshing transmission mechanism 313 fixedly installed on the outer wall of the connecting pipe. The gear meshing transmission mechanism 313 drives the connecting shaft 312 to move within the adjustment hole, thereby allowing the position of the base 311 within the connecting pipe to be adjusted along the axial direction of the connecting pipe; the seal 314 is located at the adjustment hole and is used to seal the adjustment hole after the gap size is determined.

[0069] The adjustable mounting structure employs a gear-driven transmission to mount the base, enabling vertical movement of the base, adjustable gap size, and adjustable pressure at the gap. This facilitates the rapid acquisition of a uniform post-cycle emulsion with the desired particle size within a shorter time. Furthermore, the gap size is adjustable from 5mm to 15mm, and the pressure at the gap is adjustable from 10Bar to 30Bar. The connecting shaft can utilize keyed bolts, connecting and securing it to the gear via a key to transmit torque.

[0070] Figure 5 The diagram schematically illustrates the structure of a gear meshing transmission mechanism according to an embodiment of this application. For example... Figure 5 As shown, the gear meshing transmission mechanism in this embodiment includes: a gear 3131, a first rack 3132, and a fixing member; wherein, the gear 3131 is connected to the other end of the connecting shaft 312 passing through the adjustment hole; the first rack 3132 is welded and fixed to the outer wall of the connecting pipe and meshes with the gear 3131; a screwing member is fixed on the gear 3131 for adjusting the meshing position of the gear and the first rack 3132. For example, the screwing member can be a hexagonal nut welded to the upper end of the gear. When it is necessary to adjust the gap, after removing the fixing member, the hexagonal nut can be turned with a wrench to make the gear move up or down along the first rack; after the meshing position of the gear and the first rack is determined, that is, after the base position is determined, that is, after the gap size is determined, the gear is fixed by the fixing member. In addition, as Figure 5 As shown, a scale line is provided on the first rack 3132 to facilitate gap adjustment.

[0071] Preferably, the fixing member is a second rack 3133, which is fixed to the connecting pipe and has an adjustable distance from the gear. The second rack fixes the gear by moving to mesh with it, thus easily and stably fixing the gear. Further, as... Figure 5As shown, the second rack 3133 engages with the gear 3131 and cooperates with the first rack 3132 to fix the gear 3131 between them. By cooperating with the first rack 3132, the fixing stability and reliability of the gear 3131 are further improved, thereby ensuring the stability of the pressure inside the connecting pipe 31. Specifically, the second rack 3133 is installed on the first rack 3132 through a movable connector. The first rack 3131 is used to fix the connecting pipe, and the second rack 3133 is parallel to the first rack 3132. The distance between the two is adjustable. When adjustment is needed, the second rack 3133 moves away from the gear 3131. When the position is determined, the second rack 3133 moves to engage with the gear 3131, thereby fixing the gear 3131.

[0072] Optionally, a grooved fixing strip 3134 and a matching nut are used as movable connectors for installation. The two movable connectors form an adjustable rectangular structure with the first and second racks. Both ends of the second rack 3133 are connected to the first rack 3133 via two stainless steel fixing strips 3134. A groove is provided at the end of the fixing strip 3134 connected to the second rack 3133. Nuts are used to fix both ends of the second rack 3133 to the grooves, and the distance between the first and second racks can be adjusted by loosening the nuts. Adjustment process: When the spacing needs to be adjusted, loosen the nut at the slide groove, slide the second rack to the left, away from the gear, and the meshing position of the gear and the first rack can be adjusted. Specifically, the gear can be moved up or down along the first rack by tightening the hexagonal nut. After adjusting to the determined distance, slide the second rack to the right and make it mesh with the gear, tighten the nut at the slide groove to fix the gear. After fixing the gear, use a seal to seal the adjustment hole to achieve a sealed pipeline.

[0073] Optionally, the seal 314 is a rubber sealing ring, such as... Figure 3 As shown, it can be fitted onto the connecting shaft and positioned between the outer wall of the connecting pipe 31 and the gear meshing transmission mechanism 313. Furthermore, a metal gasket 316 can be provided between the seal 314 and the gear meshing transmission mechanism 313 to prevent damage to the seal and ensure a proper seal. Additionally, as... Figure 4 As shown, a handle can be provided on the gear meshing transmission mechanism 313. Rotating the handle will compress the metal gasket 316 and the rubber sealing ring to seal the pipeline.

[0074] In a preferred embodiment of this application, a method for preparing closed-cell fat-soluble nutrient liposomes is provided, comprising:

[0075] Step S1: Add oil phase material to the oil phase mixing tank, use a vacuum pump to create a vacuum, heat and stir. Add aqueous phase material to the aqueous phase mixing tank, heat and stir.

[0076] Step S2: Turn on the rotor pump and compressed air equipment to pump the material. The oil phase material and the water phase material are accelerated through the first and second threaded conveying pipes, respectively, and then flushed and hydrated at the four-way valve. They are then accelerated through the second channel between the connecting pipe and its inner annular boss, and sprayed from the gap and the third channel into the third circulation pipe. The materials circulate and hydrate in the circulation pipeline formed by the third circulation pipe, the oil phase mixing tank, and the first threaded conveying pipe and connecting pipe, or in the circulation pipeline formed by the third circulation pipe, the water phase mixing tank, and the second threaded conveying pipe and connecting pipe. The circulation time is 5 min to 20 min, for example, 8 min, 10 min, 12 min, 14 min, 16 min, 18 min, and 20 min. This yields a primary emulsion after circulation, with small particle size and high uniformity. The particle size of the primary emulsion after circulation is 250 nm to 500 nm, and the Span coefficient is 1.0 to 6.0.

[0077] Step S3: Open the fourth port of the four-way valve and feed the recycled primary emulsion as a liposome primary emulsion into the homogenizer 200 for homogenization 1-3 times. Liposomes with a particle size of less than 200 nm can be formed at a pressure not exceeding 1000 Bar, typically between 400 Bar and 1000 Bar. Furthermore, the obtained liposomes have a particle size range of 105 nm to 155 nm and a Span coefficient range of 0.800 to 1.325. Similarly, compared with existing devices, to obtain liposomes of the same particle size, the hydration time of this application is significantly reduced, shortening it by approximately 1 / 4 to 2 / 3.

[0078] In an optional embodiment, the preparation method further includes: adjusting the position of the base in the axial direction within the connecting tube to determine the gap size to meet the preparation requirements of the primary emulsion after circulation. Preferably, the gap ranges from 5 mm to 15 mm. (Reference) Figures 2-5 As shown, first, adjust the gear meshing transmission mechanism to drive the connecting shaft to move within the adjustment hole, thereby adjusting the axial position of the base within the connecting tube and determining the clearance size; then, fix the gear using the fixing component in the gear meshing transmission structure and seal the adjustment hole with a sealing component.

[0079] In an optional embodiment, the preparation method, after determining the gap size, further includes: adjusting the pressure generated in the connecting pipe by adjusting the rotational speed of the rotor pump and / or the flow rate of the compressed air device. Further, the pressure generated at the gap in the connecting pipe is adjusted, with a pressure range of 10 Bar to 30 Bar. Based on the determined gap size, controlling the pressure generated at this gap is more advantageous for obtaining a post-cycle primary emulsion with smaller particle size and higher uniformity within a shorter circulation hydration time. For example, based on the determined gap size, the rotational speed of the rotor pump can be adjusted, with a range of 400 to 1200 r / min, to provide a material flow rate of 1.0 m / s to 2.5 m / s, allowing the material to undergo flushing hydration at this flow rate, thereby generating a certain pressure in the connecting pipe. Alternatively, based on the determined gap size and rotor pump rotational speed, the compressed air device 9 can be adjusted to generate a certain pressure at the gap.

[0080] In one specific embodiment, during liposome preparation: the rotor pump speed is adjusted to provide a material flow rate of 1000 r / min, and the pressure at the gap is adjusted to 30 Bar; a circulating primary emulsifier 100 is used for circulating hydration and primary emulsification, followed by homogenization in a homogenizer 200, which can shorten the hydration time by at least 1 / 3. The specific parameters of the circulating primary emulsifier 100 are as follows: the first and second threaded delivery pipes have four spirals inside, with a spiral depth of 2 mm and a spiral width of 8 mm; the pipe diameter * π: pitch = 1.2. The connecting pipe 31 below the annular boss is 120 mm long, the narrowing channel diameter is set to 40 mm, and the length is 150 mm. The annular boss has a 45° lower chamfer and a 30° upper chamfer. The base is cylindrical, with a diameter of 40 mm and a length of 100 mm, forming a gap of 5 mm. The circulating primary emulsifier 100 is connected to the homogenizer 200 to form a closed liposome preparation device. The homogenizing device 200 can be a high-pressure homogenizer or a high-pressure microjet. In addition, an ultrafiltration device (providing a pressure of 1 Bar to 30 Bar) can be connected after the homogenizing device 200 as needed to remove liposomes with larger particle sizes, control the distribution coefficient of liposomes, and obtain liposomes of the desired particle size by changing ultrafiltration membranes with different pore sizes.

[0081] The following is combined with Figure 1 The preparation method and operation process of closed-cell fat-soluble nutrient liposomes provided in this application are described exemplarily as follows:

[0082] Example 1 (Single-pot production):

[0083] This embodiment is a single-pot production process, with circulating hydration carried out in a closed circulation pipeline formed by the oil phase stirring and mixing tank 1. The main operation process is as follows:

[0084] 1) Add oil phase material to oil phase mixing tank 1, use vacuum pump 8 to create a vacuum, heat to 60℃ and stir; add aqueous phase material to aqueous phase mixing tank 2, heat to 60℃ and stir. At this time, valves 41, 51, 61, 62, 63 and 64 are in the closed state.

[0085] In this embodiment, the oil phase consists of phospholipids, vitamin A, vitamin D, vitamin E, and Tween 80; the aqueous phase is a buffer solution prepared from phosphates, sodium chloride, and water. Both mixing tanks are enclosed, equipped with stirring paddles, and both utilize hydrothermal heating. Figure 1 The hot water enters from the hot water inlet at the bottom of the tank and exits from the hot water outlet on the side of the tank. Furthermore, it should be noted that the heating and stirring temperature during mixing of the two batching tanks in this application is not limited to this; it can be controlled within the range of 50℃ to 65℃.

[0086] 2) After mixing is completed, valves 51 and 64 are closed, while valves 41, 61, 62, and 63 are open. Open the discharge port of oil phase mixing tank 1, the discharge port of first rotor pump 12 and water phase mixing tank 2, the discharge port of second rotor pump 22, and open the two compressed air devices 9. Under the combined action of the rotor pump and the compressed air, the oil phase and water phase obtain a high flow rate after passing through the two threaded conveying pipes. After speeding up, they are flushed and hydrated at high speed at the four-way valve 6. After passing through the four-way valve 6, they enter the connecting pipe 31 through the third interface above and rush into the narrowed second channel to obtain rapid acceleration. They are sprayed towards the base 311 and sprayed into the third circulation pipe 3 through the gap and the third channel.

[0087] After the aqueous phase in the aqueous phase mixing and batching tank 2 is emptied, valve 62 is closed, and the second rotor pump 22 is shut off. The primary emulsion is then circulated and hydrated in a closed circulation pipeline formed by the third circulation pipe 3, the fourth circulation pipe 4, the oil phase mixing and batching tank 1, the first threaded conveying pipe 11, and the connecting pipe 31. The circulation time is 10 minutes, and the resulting liquid is the primary emulsion after circulation. Samples of the primary emulsion after circulation are taken for testing, and the test results are shown in Table 2. The particle size distribution diagram is shown below. Figure 6 As shown.

[0088] 3) After a circulation time of 10 minutes, valve 63 is closed and valve 64 is opened. The primary emulsion after circulation is introduced into homogenizer 200 through the first rotor pump 12 and the compressed air device 9 connected to the oil phase stirring and mixing tank 1. Homogenization is performed three times at a pressure of 700 Bar to obtain liposomes. The liposomes are sampled and tested; the results are shown in Table 3. The particle size distribution of the liposomes is shown in the figure below. Figure 7 As shown.

[0089] Examples 2-4

[0090] The difference from Example 1 is that the hydration times were 5 min, 20 min, and 30 min, respectively. Liposomes were sampled and analyzed; the particle size and Span coefficient results are shown in Table 3.

[0091] Comparative Example 1

[0092] The difference from Example 1 is that both spiral feed pipes and connecting pipe 31 were replaced with ordinary straight pipes. Material samples were taken and tested after circulation, and the results are shown in Table 2; the Span coefficient is used to characterize the particle size distribution. The particle size distribution diagram of the liposomes is shown below. Figure 8 As shown.

[0093] Comparative Examples 2-4

[0094] These correspond to Examples 2-4, the difference being that the spiral feed tube and connecting tube in Examples 2-4 are replaced with ordinary straight tubes. The liposome sampling and testing results, including particle size and Span coefficient, are shown in Table 3.

[0095] Table 2. Particle size and Span coefficient of primary emulsion / material after cycling.

[0096] Particle size Span coefficient Example 1 (Spiral conveyor pipe + connecting pipe) 251nm 5.377 Comparative Example 1 (Ordinary straight pipe + ordinary straight pipe) 44μm 13.229

[0097] As can be seen from Table 2, compared with the ordinary straight pipe of Comparative Example 1, the circulating primary emulsion obtained by circulating hydration using the spiral conveying pipe and connecting pipe 31 of Example 1 has a much finer particle size and a smaller Span coefficient.

[0098] Table 3. Particle size and Span coefficient of liposomes

[0099]

[0100] As shown in Table 3, the circulating primary emulsification device 100, formed by the spiral delivery pipe and connecting pipe 31, can homogenize after circulating hydration, resulting in liposomes with smaller particle sizes within a shorter circulating hydration time. Compared to the comparative example, the circulating hydration time required to obtain liposomes of the same particle size is significantly reduced, by approximately 1 / 4 to 2 / 3. As shown in Example 1 and Comparative Example 4, liposomes with a diameter of 112 nm were obtained. Example 1 required only 10 minutes of circulating hydration time, while Comparative Example 4 required 30 minutes.

[0101] from Figure 6 It can be seen that the circulating primary emulsion device 100 formed by the spiral conveying pipe and the connecting pipe 31 can obtain a circulating primary emulsion with small particle size and good uniformity through circulating hydration.

[0102] from Figure 7It can be seen that homogenizing the post-cycle proemulsion significantly reduced the liposome particle size and narrowed the peak shape, resulting in a smaller distribution range and smaller liposome size with higher homogeneity.

[0103] from Figure 8 It can be seen that when the two spiral feeding tubes and connecting tube 31 are replaced with ordinary straight tubes, under the same conditions, the liposomes obtained in Comparative Example 1 have larger particle sizes and wider peak shapes, i.e., a larger distribution range and poorer uniformity.

[0104] Example 5:

[0105] This embodiment is for continuous production. The main difference from Embodiment 1 is that: circulating hydration is carried out in a closed circulation pipeline formed by the aqueous phase stirring and batching tank 2; and after the oil phase is emptied, the next batch of material is prepared in the oil phase stirring and batching tank 1. The main operating procedures are as follows:

[0106] 1) Add oil phase material to oil phase mixing tank 1, use vacuum pump 8 to create a vacuum, heat to 50℃~65℃ and stir; add aqueous phase material to aqueous phase mixing tank 2, heat to 50℃~65℃ and stir. Valves 41, 51, 61, 62, 63, and 64 are in the closed state.

[0107] 2) After stirring, valves 41 and 64 are closed, and valves 51, 61, 62, and 63 are open. Open the discharge port of batching tank 1, the discharge port of the first rotor pump 12 and batching tank 2, and the second rotor pump 22. Turn on the two compressed air devices 9. Under the combined action of the rotor pumps and the compressed air, the oil phase and water phase obtain a high flow rate after passing through the two threaded conveying pipes. After speeding up, they are hydrated at high speed at the four-way valve 6 to form a primary emulsion. After passing through the four-way valve 6, it enters the connecting pipe 31 through the third interface above and rushes into the narrowing channel to obtain rapid acceleration. It is sprayed towards the base 311. After intermittent spraying and impact, it is sprayed from the outer periphery of the base 311 into the third circulation pipe 3.

[0108] After the oil phase in the oil phase mixing and batching tank 1 is emptied, valve 61 is closed, the discharge port of the batching tank 1 is closed, the first rotor pump 12 is shut down, and the compressed air equipment 9 connected to the oil phase mixing and batching tank 1 is shut down. The primary emulsion is hydrated and circulated in the circulation pipeline formed by the third circulation pipe 3, the fifth circulation pipe 5, the water phase mixing and batching tank 2, the second threaded conveying pipe 21, and the connecting pipe 31 for 10 minutes, resulting in a circulated primary emulsion. At the same time, the next batch of materials is prepared in the oil phase mixing and batching tank 1.

[0109] 3) Close valve 63 and open valve 64. The circulating primary emulsion is fed into homogenizer 200 through the second rotor pump 22 and the compressed air device 9 connected to the aqueous phase mixing tank 2. The emulsion is homogenized twice at a pressure of 400 Bar to 1000 Bar. The resulting liposomes are then sent to an ultrafiltration device to remove larger liposomes.

[0110] The description of this invention is given for illustrative and descriptive purposes only and is not intended to be exhaustive or to limit the invention to the forms disclosed. Many modifications and variations will be apparent to those skilled in the art. The embodiments were chosen and described in order to better illustrate the principles and practical application of the invention and to enable those skilled in the art to understand the invention and to design various embodiments with various modifications suitable for a particular purpose.

Claims

1. A closed-loop apparatus for preparing fat-soluble nutrient liposomes, characterized in that, Includes homogenizing equipment and a circulating primary emulsifier connected to its inlet; The circulating primary emulsification device includes: an oil phase stirring and batching tank and a first threaded conveying pipe connected to its outlet; an aqueous phase stirring and batching tank and a second threaded conveying pipe connected to its outlet; a third circulation pipe; a fourth circulation pipe; and a fifth circulation pipe; wherein... The first and second threaded conveying pipes are connected to each other via a four-way valve. This allows the oil phase material and the water phase material to be accelerated through the first and second threaded conveying pipes respectively, and then flushed and hydrated at the four-way valve. The third port of the four-way valve is connected to one end of the third circulation pipe via a connecting pipe, and the fourth port of the four-way valve is connected to the homogenizing equipment. The inner wall of the connecting pipe narrows inward to form an annular boss. A second channel is formed in the middle of the annular boss, so that the flushed and hydrated material is accelerated through the second channel between the connecting pipe and the annular boss and sprayed into the third circulation pipe for circulating hydration in the circulation pipeline. The other end of the third circulation pipe is connected to the fourth and fifth circulation pipes respectively via a three-way valve. The fourth circulation pipe is connected to the oil phase mixing and batching tank, and the fifth circulation pipe is connected to the water phase mixing and batching tank. The oil phase mixing and batching tank and the water phase mixing and batching tank are also connected to a vacuum pump and a compressed air device. The outlets of the oil phase mixing and batching tank and the water phase mixing and batching tank are equipped with rotor pumps for pumping materials.

2. The closed-type fat-soluble nutrient liposome preparation device according to claim 1, characterized in that, The connecting pipe is also provided with a coaxial base. The base is located on the side where the annular boss is connected to the third circulation pipe, and a gap is formed between the base and the end face of the annular boss on the same side. The outer periphery of the base forms a third channel with the inner wall of the connecting pipe.

3. The closed-type fat-soluble nutrient liposome preparation device according to claim 2, characterized in that, The base is adjustablely mounted on the connecting pipe, and its position along the axial direction of the connecting pipe is adjustable, so that the size of the gap can be adjusted to regulate the pressure inside the connecting pipe.

4. The closed-type fat-soluble nutrient liposome preparation device according to claim 3, characterized in that, The base is adjustablely mounted on the connecting pipe via an adjustable mounting structure, which includes a connecting shaft, a gear meshing transmission mechanism, and a seal. The connecting pipe has an adjustment hole on its wall; the connecting shaft passes through the adjustment hole, with one end connected to the base inside the connecting pipe and the other end connected to a gear meshing transmission mechanism fixedly installed on the outer wall of the connecting pipe. The gear meshing transmission mechanism is used to drive the connecting shaft to move within the adjustment hole, thereby making the axial position of the base within the connecting pipe adjustable; the sealing element is provided at the adjustment hole and is used to seal the adjustment hole after the gap size is determined.

5. The closed-type fat-soluble nutrient liposome preparation device according to claim 4, characterized in that, The gear meshing transmission mechanism includes: a gear, a first rack, and a fixing member; the gear is connected to the other end of a connecting shaft; the first rack is fixed on the outer wall of a connecting pipe and meshes with the gear; a screwing member is fixed on the gear for adjusting the meshing position of the gear and the first rack; the fixing member is used to fix the gear after the meshing position of the gear and the first rack is determined. Alternatively, the fixing element is a second rack, which is fixed to the connecting pipe and the distance between the second rack and the gear is adjustable. The second rack fixes the gear by moving to mesh with the gear.

6. The closed-type fat-soluble nutrient liposome preparation device according to claim 5, characterized in that, The second rack is mounted on the first rack via a movable connector, is parallel to the first rack and the distance between the two racks is adjustable, and the two racks are located on opposite sides of the gear.

7. The closed-type fat-soluble nutrient liposome preparation device according to claim 3, characterized in that, The adjustable range of the gap is 5mm to 15mm, and a pressure gauge is installed at the connecting pipe to detect the pressure inside the connecting pipe. And / or, the oil phase mixing tank and the water phase mixing tank are arranged horizontally and symmetrically distributed on both sides of the third circulation pipe.

8. The closed-type fat-soluble nutrient liposome preparation device according to claim 2, characterized in that, The first threaded conveying pipe and the second threaded conveying pipe have the same structure, with 2 to 8 spirals inside, spiral depth of 1 mm to 3 mm, spiral width of 5 mm to 20 mm, and pipe diameter * π: pitch = 0.4 to 2.80; And / or, the end faces on both sides of the annular boss are chamfered; the base is a cylinder with a diameter larger than the diameter of the second channel formed inside the annular boss and smaller than the inner diameter of the connecting pipe; wherein, the diameter of the second channel formed inside the annular boss is 30mm to 50mm; the diameter of the base is 35mm to 55mm; the length of the annular boss is 100mm to 200mm; the length of the base is 80mm to 180mm; the length of the connecting pipe on the side where the annular boss connects to the third interface of the four-way valve is 100mm to 150mm; the length of the connecting pipe on the side where the annular boss connects to the third circulation pipe is 350mm to 400mm.

9. A method for preparing closed-cell fat-soluble nutrient liposomes, characterized in that, The preparation is carried out using the closed-type fat-soluble nutrient liposome preparation apparatus according to any one of claims 2-8, comprising: Add oil phase material to the oil phase mixing tank, use a vacuum pump to create a vacuum, heat and stir; add aqueous phase material to the aqueous phase mixing tank, heat and stir. Turn on the rotor pump and compressed air equipment to pump the material. The oil phase material and the water phase material are accelerated through the first threaded conveying pipe and the second threaded conveying pipe respectively. They are flushed and hydrated at the four-way valve. They are accelerated through the second channel between the connecting pipe and the inner annular boss, and sprayed from the gap and the third channel to the third circulation pipe. They are hydrated in the circulation pipeline formed by the third circulation pipe, the oil phase stirring and batching tank and the first threaded conveying pipe and the connecting pipe, or the circulation pipeline formed by the third circulation pipe, the water phase stirring and batching tank and the second threaded conveying pipe and the connecting pipe, to obtain the circulating primary emulsion. Open the fourth port of the four-way valve, and the circulating primary emulsion enters the homogenizer for homogenization to form liposomes.

10. The method for preparing closed-cell fat-soluble nutrient liposomes according to claim 9, characterized in that, Also includes: Adjust the position of the base in the axial direction inside the connecting pipe to determine the clearance size; adjust the speed of the rotor pump and / or the flow rate of the compressed air equipment to adjust the pressure generated inside the connecting pipe; The rotor pump's rotational speed is adjusted to provide a material flow rate of 0.1 m / s to 2.5 m / s; the pressure generated at the gap in the connecting pipe is adjusted to 10 Bar to 30 Bar.

11. The method for preparing closed-cell fat-soluble nutrient liposomes according to claim 10, characterized in that, The step of adjusting the position of the base in the axial direction within the connecting pipe and determining the gap size includes: adjusting the gear meshing transmission mechanism to drive the connecting shaft to move within the adjustment hole, thereby adjusting the position of the base in the axial direction within the connecting pipe and determining the gap size; after determining the gap size, fixing the gear through the fixing component in the gear meshing transmission structure and sealing the adjustment hole with a sealing component.

12. The method for preparing closed-cell fat-soluble nutrient liposomes according to claim 9, characterized in that, The step after speeding up via the first and second threaded conveying pipes refers to increasing the material flow rate by at least 3.5%. And / or, during cyclic hydration, the cyclic time is 5 min to 20 min, and the resulting primary emulsion after cyclic hydration has a particle size of 250 nm to 500 nm and a Span coefficient of 1.0 to 6.

0. During homogenization, the homogenization pressure is 400 Bar to 1000 Bar, and the number of homogenization cycles is 1 to 3; the particle size of the liposomes is 105 nm to 155 nm; and the Span coefficient is 0.800 to 1.325.

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