A microfluidic device for preparing water-soluble nanocrystals with high curcumin loading and a method thereof.

Abstract

This invention discloses a microfluidic device for preparing water-soluble nanocrystals with high curcumin loading and a method thereof, relating to the field of nanocrystal processing technology. The microfluidic device includes a molecular assembly section and a nanocrystal assembly section. The molecular assembly section includes a feed microchannel and a molecular assembly channel, and the nanocrystal assembly section includes at least one nanocrystal assembly channel with a helical reflux structure. The method includes: S1, preparing a soy protein isolate solution, a rhamnolipin solution, and a curcumin solution; S2, introducing them separately into the feed microchannel, where the soy protein isolate solution and the rhamnolipin solution are first mixed, and then introduced together with the curcumin solution into the molecular assembly channel for mixing and molecular assembly; S3, continuing to introduce the solution into the nanocrystal assembly channel for nanocrystal assembly, thus obtaining the nanocrystals. This invention uses microfluidic technology combined with a pH-driven method to successfully achieve highly precise control over the size of the nanocrystals, significantly improving the encapsulation efficiency, loading capacity, and water solubility of the nanocrystals.

Description

Technical Field

[0001] This invention relates to the field of nanocrystal processing technology, specifically to a microfluidic device for preparing water-soluble nanocrystals with high curcumin loading and a method thereof. Background Technology

[0002] Curcumin is a hydrophobic bioactive substance extracted from the rhizomes of plants in the ginger and araceae families. As a rare, naturally occurring orange-yellow colorant with a diketone structure, it possesses low toxicity and broad-spectrum biological and pharmacological activities, such as antioxidant, anti-inflammatory, anticancer, and antibacterial activities. Therefore, curcumin exhibits great application potential. However, curcumin has extremely low solubility and bioavailability in acidic environments and is easily degraded under light or high temperatures, severely limiting its applications. Therefore, improving the solubility and stability of curcumin is an urgent problem to be solved.

[0003] Nanocrystals refer to tiny particles with diameters in the nanometer range. Compared to ordinary micrometer-sized particles, nanocrystals possess unique characteristics such as small size and large specific surface area, making them widely used to encapsulate lipid-soluble bioactive substances to improve their water solubility and bioavailability. This gives nanocrystals broad application prospects in numerous fields, especially in the delivery of functional bioactive substances. As the application prospects of nanocrystals continue to expand, various methods for their preparation have emerged. However, most existing nanocrystal preparation methods use organic solvents, which may cause certain biotoxic effects, thus affecting their biosafety. Furthermore, nanocrystals prepared by existing methods also suffer from low encapsulation efficiency and loading capacity.

[0004] pH-driven methods control the formation and assembly of nanoparticles by adjusting the pH of the solution. This method utilizes the property that the solubility and charge of a solute change with pH, ​​causing intermolecular interactions and spontaneous assembly into stable nanocrystals as the pH changes. Compared to traditional chemical methods, pH-driven methods are simple, efficient, and do not require organic solvents, making them promising for large-scale production in the food industry. However, as a thermodynamic self-assembly method, the nanoparticles prepared by pH-driven methods lack stability in mass production and are prone to aggregation or precipitation. Furthermore, the encapsulation efficiency and loading capacity of the nanocrystals are relatively low, affecting their controlled-release effect.

[0005] Microfluidics is an emerging interdisciplinary field involving chemistry, fluid physics, new materials, and biomedical engineering. Compared to traditional thermodynamically controlled nanocrystal preparation processes, microfluidic technology offers advantages such as strong controllability, high reaction efficiency, high throughput, high integration, and strong repeatability. However, existing microfluidic devices generally have poor nanocrystal assembly results. This may be due to the unreasonable structure of existing microfluidic devices, leading to uncontrollable precipitation caused by excessively high or low local pH within the channels. This prevents the uniform encapsulation of bioactive substances and biopolymers, thus failing to obtain uniformly distributed and structurally stable nanocrystals. Summary of the Invention

[0006] The purpose of this invention is to at least solve one of the technical problems existing in the prior art, namely, the problems of curcumin crystals or curcumin complexes having "extremely low solubility and bioavailability, low encapsulation efficiency and loading capacity, easy degradation under light or high temperature conditions, and potential biotoxicity of organic solvents", and to provide a microfluidic device for preparing water-soluble nanocrystals with high curcumin loading and a method thereof.

[0007] This invention designs a microfluidic device. The microchannel design of this device shortens the mixing length and time for nanocrystal self-assembly and prevents excessive aggregation or precipitation of nanocrystals. In this process, curcumin is dissolved in an alkaline solution, while the biopolymer is dissolved in an acidic solution. By adjusting parameters such as the inner diameter of the microfluidic chip's channels and the fluid flow rate, rapid mass exchange is achieved, allowing curcumin and the biopolymer to be controllably assembled into nanocrystals under non-covalent interactions. The use of organic solvents is avoided throughout the preparation process. This invention uses soy protein isolate / rhamnolipin nanocrystals as a water-soluble biopolymer carrier for curcumin. Soy protein isolate primarily provides a stable carrier environment and improves bioavailability, while rhamnolipin acts as an effective surfactant, enhancing the solubility and absorption efficiency of curcumin in vivo. The ternary composite nanocrystals prepared by this invention are assembled through hydrogen bonding and hydrophobic interactions. The preparation process is simple, rapid, safe, and efficient, showing broad application prospects in the food, cosmetics, and pharmaceutical fields.

[0008] The technical solution of the present invention is as follows:

[0009] The first aspect of this invention provides a method for preparing water-soluble nanocrystals with high curcumin loading using a microfluidic device.

[0010] The microfluidic device includes a molecular assembly section and a nanocrystal assembly section. The molecular assembly section includes a feed microchannel and a molecular assembly channel. The nanocrystal assembly section includes at least one nanocrystal assembly channel with a spiral reflux structure. The feed microchannel, the molecular assembly channel and the nanocrystal assembly channel are connected in sequence. The feed microchannel has a feed inlet and the nanocrystal assembly channel has a discharge outlet.

[0011] The method for preparing water-soluble nanocrystals with high curcumin loading using the microfluidic device includes the following steps:

[0012] S1. Dissolve soy protein isolate in an aqueous solution and refrigerate to obtain a soy protein isolate solution; dissolve rhamnolipin in an aqueous solution to obtain a rhamnolipin solution; dissolve curcumin in an aqueous solution and sonicate to obtain a curcumin solution.

[0013] S2. The soy protein isolate solution, rhamnolipin solution and curcumin solution are introduced into the feed microchannel through the feed inlet, wherein the soy protein isolate solution and rhamnolipin solution are mixed first, and then mixed together with the curcumin solution in the molecular assembly channel for molecular assembly.

[0014] S3. Continue to enter the nanocrystal assembly channel to assemble nanocrystals and obtain water-soluble nanocrystals with high curcumin loading.

[0015] Preferably, in step S1, the mass ratio of curcumin to soy protein isolate and rhamnolipin is 1:2 to 8:2 to 8.

[0016] Preferably, in step S1,

[0017] Weigh out soy protein isolate with a purity >90% and dissolve it in an aqueous solution. After it is fully dissolved, refrigerate it at 0-4℃ for 8-24 hours. Adjust the pH to 2-3 using 0.1-2 mol / L HCl to obtain a soy protein isolate solution with a concentration of 7-9%.

[0018] Weigh out rhamnolipin with a purity >95% and dissolve it in an aqueous solution. Adjust the pH to 2-3 using 0.1-2 mol / L HCl to obtain a rhamnolipin solution with a concentration of 7-9%.

[0019] Weigh out curcumin with a purity >95%, dissolve it in an aqueous solution with pH = 11-12, and sonicate for 4-6 minutes to obtain a curcumin solution of 3.0-5.0 mg / mL.

[0020] Preferably, the inner diameter of the feeding microchannel, the molecular assembly channel, and the nanocrystal assembly channel is 0.5–1.2 mm, and the flow rates of the soy protein isolate solution, rhamnolipin solution, and curcumin solution in the molecular assembly channel and the nanocrystal assembly channel are 0.7–0.9 m / s.

[0021] Preferably, the feeding microchannel includes a first feeding microchannel and a second feeding microchannel. The feeding end of the first feeding microchannel has a first feeding port. The feeding end of the second feeding microchannel has a second feeding port and a third feeding port. The discharging ends of the first feeding microchannel and the second feeding microchannel are both connected to the feeding end of the molecular assembly channel.

[0022] In step S2, curcumin solution is introduced into the first feed microchannel through the first feed port, and soy protein isolate solution and rhamnolipin solution are introduced into the second feed microchannel through the second feed port and the third feed port, respectively. The soy protein isolate solution and rhamnolipin solution are first mixed in the second feed microchannel, and then mixed together with the curcumin solution in the first feed microchannel into the molecular assembly channel for molecular assembly.

[0023] Preferably, the first feeding microchannel is circular or arc-shaped, the first feed port and the molecular assembly channel are respectively located at both ends of the first feeding microchannel, and the second feeding microchannel includes two feeding channels and one mixing channel. The two feeding channels and the mixing channel are all set at an angle, and the mixing channel is arranged in a straight line with the molecular assembly channel.

[0024] Preferably, the nanocrystal assembly channel includes a first arc, a second arc, a third arc, a fourth arc, and a fifth arc connected in sequence. The openings of the first, third, and fifth arcs face upwards, while the openings of the second and fourth arcs face downwards. The first, second, and fifth arcs all extend in a direction away from the molecular assembly segment, and the third and fourth arcs both extend in a direction closer to the molecular assembly segment to form a spiral reflux structure. The sum of the diameters of the third and fourth arcs is smaller than the diameter of the second arc.

[0025] Preferably, the radii of the first arc, the second arc, the third arc, the fourth arc, and the fifth arc are 7-8 cm, 12-13 cm, 3-4 cm, 3-4 cm, and 7-8 cm, respectively.

[0026] Preferably, the number of nanocrystal assembly channels is 2 to 6, and the 2 to 6 nanocrystal assembly channels are connected sequentially to form the nanocrystal assembly segment.

[0027] A second aspect of the present invention provides water-soluble nanocrystals with high curcumin loading, which are prepared by the method described above.

[0028] The nanocrystals of the present invention have a particle size of 50-160 nm, an encapsulation efficiency of curcumin greater than 90%, and a loading capacity of curcumin greater than 7%.

[0029] This invention has at least one of the following beneficial effects:

[0030] 1. This invention innovatively employs microfluidic technology combined with a pH-driven method to successfully achieve highly precise control over the size of nanocrystals, significantly improving their encapsulation efficiency, loading capacity, and water solubility. Based on a helical reflux microfluidic chip, this invention prepares nanocrystals with high consistency and good stability. By using a specific biopolymer as the wall material, hydrophobic bioactive substances such as curcumin can be efficiently encapsulated, thereby significantly improving their encapsulation efficiency, loading capacity, stability, solubility, and bioavailability. Microfluidic technology itself has the advantages of simple operation and low energy consumption, and no organic solvents are used in the entire preparation process, making it particularly suitable for applications in the food, cosmetics, and pharmaceutical industries. Compared with the traditional pH-driven method, this innovative preparation method can produce curcumin nanocrystals with higher encapsulation efficiency and loading capacity, significantly improving the bioavailability and stability of curcumin. This technological breakthrough lays the foundation for the widespread application of curcumin in the food and pharmaceutical fields.

[0031] 2. In the preparation method of this invention, rhamnolipid is first inserted into the hydrophobic pocket of soy protein isolate and linked to the amino acid residues of soy protein isolate through hydrogen bonds and hydrophobic interactions to form a binary complex. The binary complex further binds with curcumin through hydrogen bonds and hydrophobic interactions to form a ternary complex. These non-covalent interactions not only stabilize the structure of the complex but also improve the water solubility of curcumin and enhance its biocompatibility.

[0032] 3. This invention systematically characterizes and compares the effects of the combined application of microfluidic technology and pH-driven method, as well as the use of pH-driven method alone, on nanodelivery systems, laying a theoretical foundation for the development of more efficient nanodrug delivery systems.

[0033] 4. This invention innovates a method for preparing nanocrystals. This method is simple and efficient, requires no organic solvents, and uses a carrier with good biocompatibility. These advantages make this method have significant economic and environmental benefits, and are very conducive to commercial applications. Attached Figure Description

[0034] Figure 1 This is a schematic diagram of the microfluidic device in Embodiment 1 of the present invention;

[0035] Figure 2 This is a partial structural schematic diagram of the microfluidic device in Embodiment 1 of the present invention;

[0036] Figure 3The following are schematic diagrams of the microfluidic devices in Comparative Examples 4 to 6 of the present invention, wherein A is a schematic diagram of the microfluidic device in Comparative Example 4, B is a schematic diagram of the microfluidic device in Comparative Example 5, and C is a schematic diagram of the microfluidic device in Comparative Example 6.

[0037] Figure label:

[0038] 1. Molecular assembly section; 11. First feed microchannel; 12. Second feed microchannel; 13. Molecular assembly channel; 14. First feed inlet; 15. Second feed inlet; 16. Third feed inlet;

[0039] 2. Nanocrystal assembly section; 21. Nanocrystal assembly channel; 22. First arc; 23. Second arc; 24. Third arc; 25. Fourth arc; 26. Fifth arc; 27. Discharge port.

[0040] Figure 4 This is a scanning electron microscope image of the nanocrystals prepared in Example 1 of the present invention;

[0041] Figure 5 This is a scanning electron microscope image of the nanocrystals prepared in Example 2 of the present invention;

[0042] Figure 6 This is a scanning electron microscope image of the nanocrystals prepared in Example 3 of the present invention;

[0043] Figure 7 This is a scanning electron microscope image of the nanocrystals prepared in Comparative Example 1 of the present invention;

[0044] Figure 8 This is a scanning electron microscope image of the nanocrystals prepared in Comparative Example 2 of the present invention;

[0045] Figure 9 This is a scanning electron microscope image of the nanocrystals prepared in Comparative Example 3 of the present invention;

[0046] Figure 10 This is a scanning electron microscope image of the nanocrystals prepared in Comparative Example 4 of the present invention;

[0047] Figure 11 This is a scanning electron microscope image of the nanocrystals prepared in Comparative Example 5 of the present invention;

[0048] Figure 12 This is a scanning electron microscope image of the nanocrystals prepared in Comparative Example 6 of this invention;

[0049] Figure 13 This is a scanning electron microscope image of the nanocrystals prepared in Comparative Example 7 of this invention. Detailed Implementation

[0050] To make the technical problems solved, the technical solutions, and the beneficial effects of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0051] One embodiment of the present invention provides a method for preparing water-soluble nanocrystals with high curcumin loading using a microfluidic device.

[0052] like Figures 1-2 As shown, the microfluidic device includes a molecular assembly section 1 and a nanocrystal assembly section 2. The molecular assembly section 1 includes a feed microchannel and a molecular assembly channel 13, and the nanocrystal assembly section 2 includes at least one nanocrystal assembly channel 21. The feed microchannel, the molecular assembly channel 13 and the nanocrystal assembly channel 21 are connected in sequence. The feed microchannel has a feed inlet, and the nanocrystal assembly channel 21 has a discharge outlet 27. The nanocrystal assembly channel 21 has a spiral reflux structure.

[0053] The method for preparing water-soluble nanocrystals with high curcumin loading using the microfluidic device includes the following steps:

[0054] S1. Dissolve soy protein isolate in an aqueous solution and refrigerate to obtain a soy protein isolate solution; dissolve rhamnolipin in an aqueous solution to obtain a rhamnolipin solution; dissolve curcumin in an aqueous solution and sonicate to obtain a curcumin solution.

[0055] S2. The soy protein isolate solution, rhamnolipin solution and curcumin solution are introduced into the feed microchannel through the feed inlet, wherein the soy protein isolate solution and rhamnolipin solution are first mixed, and then the soy protein isolate solution and curcumin solution are introduced into the molecular assembly channel 13 for mixing and molecular assembly.

[0056] S3. Continue to enter the nanocrystal assembly channel 21 to assemble nanocrystals and obtain water-soluble nanocrystals with high curcumin loading.

[0057] Figure 1 This is a schematic diagram of the microfluidic device with a spiral reflux structure used in this invention. When the three-phase solutions converge, although the flow resistance is relatively large, due to the differences in physical properties between the three phases (density, viscosity, surface tension, etc.) and the presence of obstacles, local velocity acceleration or deceleration may occur near the confluence point, forming two different flow modes: laminar flow and turbulent flow. This change in flow behavior is beneficial to improving the mass transfer efficiency between fluids, reducing mixing time, and improving the fluid mixing effect. The specific principle is as follows:

[0058] Molecular Assembly Stage: The main function of this stage is to ensure the uniform distribution of different molecules. Through precise control using a microfluidic chip, efficient mixing of fluids within microchannels can be achieved. During this stage, the mixed molecules begin to undergo preliminary chemical reactions, such as coordination, ionic bond formation, or the formation of other chemical bonds. Furthermore, reaction conditions can be optimized by controlling parameters such as pH, concentration, and flow rate to create ideal conditions for subsequent assembly processes, ensuring their smooth progress. During molecular assembly, rhamnolipids first insert into the hydrophobic pocket of soy protein isolate and bind to the amino acid residues of soy protein isolate through hydrogen bonds and hydrophobic interactions, forming a binary complex. This binding sequence provides more binding sites for curcumin within the binary complex, contributing to the formation of a stable ternary complex. The binary complex then binds to curcumin through hydrogen bonds and hydrophobic interactions, forming a ternary complex. These non-covalent interactions not only stabilize the complex structure but also improve the water solubility and bioavailability of curcumin.

[0059] Nanocrystal Assembly Stage: This stage primarily utilizes the precise control capabilities of microfluidics to achieve the ordered assembly and precise positioning of nanocrystals in a microscale environment. This process begins with the nucleation stage of nanocrystals in solution, where the initial nuclei gradually grow and eventually evolve into stable nanocrystal structures. Microfluidics precisely controls the flow rate, volume, and other flow conditions of the fluid, enabling precise manipulation of molecular motion and positioning. This allows for the accurate assembly of nanocrystals into nanostructures with specific sizes and functions, while simultaneously ensuring uniform dispersion of the nanocrystals in the solution and preventing aggregation.

[0060] In some specific embodiments of the present invention, in step S1, the mass ratio of curcumin to soy protein isolate and rhamnolipid is 1:2 to 8:2 to 8. Preferably, it is 1:3 to 7:3 to 7, and more preferably, it is 1:4 to 6:4 to 6.

[0061] In some specific embodiments of the present invention, in step S1,

[0062] Weigh out soy protein isolate with a purity >90% and dissolve it in an aqueous solution. After it is fully dissolved, refrigerate it at 0-4℃ for 8-24 hours. Adjust the pH to 2-3 using 0.1-2 mol / L HCl to obtain a soy protein isolate solution with a concentration of 7-9%.

[0063] Preferably, after complete dissolution, the mixture is refrigerated at 1–4°C for 12–24 hours, and the pH is adjusted to 2.2–2.8 using 1–2 mol / L HCl to obtain a soy protein isolate solution with a concentration of 7.5–8.5%.

[0064] More preferably, after complete dissolution, the mixture is refrigerated at 3-4°C for 16-24 hours, and the pH is adjusted to 2.4-2.6 using 1-2 mol / L HCl to obtain a soy protein isolate solution with a concentration of 7.7-8.3%.

[0065] In some specific embodiments of the present invention, in step S1,

[0066] Weigh out rhamnolipin with a purity >95% and dissolve it in an aqueous solution. Adjust the pH to 2-3 using 0.1-2 mol / L HCl to obtain a rhamnolipin solution with a concentration of 7-9%.

[0067] Preferably, rhamnolipin with a purity >95% is weighed and dissolved in an aqueous solution, and the pH is adjusted to 2.2-2.8 using 1-2 mol / L HCl to obtain a rhamnolipin solution with a concentration of 7.5-8.5%.

[0068] More preferably, rhamnolipin with a purity >95% is weighed and dissolved in an aqueous solution, and the pH is adjusted to 2.4-2.6 using 1-2 mol / L HCl to obtain a rhamnolipin solution with a concentration of 7.7-8.3%.

[0069] In some specific embodiments of the present invention, in step S1,

[0070] Weigh out curcumin with a purity >95%, dissolve it in an aqueous solution with pH = 11-12, and sonicate for 4-6 minutes to obtain a curcumin solution of 3.0-5.0 mg / mL.

[0071] Preferably, curcumin with a purity >95% is weighed, dissolved in an aqueous solution with pH = 11.4-12, and sonicated for 4.5-5.5 minutes to obtain a curcumin solution of 3.5-4.5 mg / mL.

[0072] Preferably, curcumin with a purity >95% is weighed, dissolved in an aqueous solution with pH = 11.6-12, and sonicated for 4.8-5.2 minutes to obtain a curcumin solution of 3.7-4.3 mg / mL.

[0073] In some specific embodiments of the present invention, the inner diameter of the feeding microchannel, the molecular assembly channel 13, and the nanocrystal assembly channel 21 is 0.5-1.2 mm, and the flow rates of the soybean protein isolate solution, rhamnolipin solution, and curcumin solution in the molecular assembly channel 13 and the nanocrystal assembly channel 21 are 0.7-0.9 m / s.

[0074] In another embodiment of the present invention, a water-soluble nanocrystal with high curcumin loading was prepared by the above method. The nanocrystal has a particle size of 50-160 nm, an encapsulation rate of curcumin greater than 90%, and a curcumin loading capacity greater than 7%.

[0075] The present invention will be further described in detail below with reference to specific embodiments, but the present invention is not limited to the following specific embodiments.

[0076] Example 1

[0077] like Figures 1-2 The diagram shows the structure of the microfluidic device in this embodiment, comprising two parts: a molecular assembly section 1 and a nanocrystal assembly section 2. The main function of the molecular assembly section 1 is to ensure the uniform distribution of different molecules. Through the precise control of the microfluidic chip, efficient mixing of fluids within the microchannels can be achieved. The nanocrystal assembly section 2 utilizes the precise control capabilities of microfluidic technology to achieve the ordered assembly and precise positioning of nanocrystals in a microscale environment. The specific structure is as follows:

[0078] The molecular assembly section 1 includes a feeding microchannel and a molecular assembly channel 13. In this embodiment, the feeding microchannel includes a first feeding microchannel 11 and a second feeding microchannel 12. The feeding end of the first feeding microchannel 11 has a first feeding port 14; the feeding end of the second feeding microchannel 12 has a second feeding port 15 and a third feeding port 16. The discharge ends of the first feeding microchannel 11 and the discharge ends of the second feeding microchannel 12 are both connected to the feeding end of the molecular assembly channel 13.

[0079] The first feeding microchannel 11 is circular or arc-shaped, and in this embodiment it is circular. The first feed port 14 and the molecular assembly channel 13 are respectively located at both ends of the first feeding microchannel 11. The second feeding microchannel 12 includes two feeding channels and one mixing channel. The two feeding channels and the mixing channel are all set at an angle, and the mixing channel and the molecular assembly channel 13 are arranged in a straight line.

[0080] The nanocrystal assembly section 2 includes a nanocrystal assembly channel 21, which is connected to the molecular assembly channel 13. The nanocrystal assembly channel 21 has a discharge port 27 and has a spiral reflux structure. Specifically, the structure of the nanocrystal assembly channel 21 is as follows:

[0081] The nanocrystal assembly channel 21 includes a first arc 22, a second arc 23, a third arc 24, a fourth arc 25, and a fifth arc 26 connected in sequence. The openings of the first arc 22, the third arc 24, and the fifth arc 26 face upwards, while the openings of the second arc 23 and the fourth arc 25 face downwards. In this embodiment, "opening upwards" and "opening downwards" refer to... Figure 1The horizontal direction is a horizontal line, with the opening facing upwards and the opening facing downwards. The first arc 22, the second arc 23, and the fifth arc 26 all extend away from the molecular assembly segment 1, while the third arc 24 and the fourth arc 25 extend towards the molecular assembly segment 1, forming a spiral reflux structure. The sum of the diameters of the third arc 24 and the fourth arc 25 is less than the diameter of the second arc 23, thus the third arc 24 and the fourth arc 25 form a spiral reflux structure.

[0082] like Figure 2 As shown, the radii of the first arc 22, the second arc 23, the third arc 24, the fourth arc 25, and the fifth arc 26 are 7–8 cm respectively. Figure 2 R1), 12-13cm ( Figure 2 R2), 3-4cm ( Figure 2 R3), 3-4cm ( Figure 2 R4 in the middle and 7-8cm ( Figure 2 The radius of R5 in the figure can be determined according to the actual situation. In this embodiment, the radii of the first arc 22, the second arc 23, the third arc 24, the fourth arc 25 and the fifth arc 26 are 8cm, 13cm, 4cm, 4cm and 8cm respectively.

[0083] The number of nanocrystal assembly channels 21 can be multiple, such as 2 to 6, and the 2 to 6 nanocrystal assembly channels 21 are connected in sequence. In this embodiment, the number of nanocrystal assembly channels 21 is 4, and the 4 nanocrystal assembly channels 21 are connected in sequence to form nanocrystal assembly segment 2, which helps the material to assemble nanocrystals therein to form water-soluble nanocrystals.

[0084] The inner diameters of the feeding microchannel, molecular assembly channel 13, and nanocrystal assembly channel 21 are adjustable from 0.5 to 1.2 mm. In this embodiment, the inner diameters of the feeding microchannel, molecular assembly channel 13, and nanocrystal assembly channel 21 are 1 mm, but the specific diameters can be selected according to actual conditions.

[0085] The method for preparing water-soluble nanocrystals with high curcumin loading using the above-mentioned microfluidic device includes the following steps:

[0086] Step 1: Weigh out soy protein isolate with a purity >90% and dissolve it in an aqueous solution to prepare an 8% soy protein isolate solution. After fully dissolving, place it in a refrigerator at 4°C overnight to fully hydrate and obtain the soy protein isolate solution.

[0087] Step 2: Dissolve rhamnolipin with a purity >95% in an aqueous solution to prepare an 8% rhamnolipin solution.

[0088] Step 3: Weigh curcumin with a purity >95% and dissolve it in an aqueous solution with pH=12. Sonicate for five minutes to dissolve all the curcumin and obtain a curcumin solution of 4.0 mg / mL.

[0089] Step 4: Before use, dilute the soy protein isolate solution and rhamnolipin solution separately and adjust their pH to 2. The final mass ratio of curcumin to soy protein isolate and rhamnolipin is 1:8:2.

[0090] Step 5: Inject curcumin solution, soy protein isolate solution, and rhamnolipid solution into the microfluidic device using a syringe pump, with the flow rate set to 0.8 m / s for each. The specific method is as follows:

[0091] The curcumin solution is fed into the first feed microchannel 11 through the first feed port 14. The curcumin solution is divided into two parts in the first feed microchannel 11 and enters through the half-circular arc respectively.

[0092] Soy protein isolate solution and rhamnolipin solution are introduced into the second feed microchannel 12 through the second feed port 15 and the third feed port 16, respectively; the soy protein isolate solution and rhamnolipin solution are first mixed in the second feed microchannel 12;

[0093] The mixed soy protein isolate solution and rhamnolipin solution were introduced into molecular assembly channel 13 together with curcumin solution and mixed for molecular assembly.

[0094] After molecular assembly, curcumin, soy protein isolate, and rhamnolipids continue to enter the nanocrystal assembly channel 21. Since the nanocrystal assembly channel 21 has a spiral reflux structure, the curcumin, soy protein isolate, and rhamnolipids continue to assemble into nanocrystals in the nanocrystal assembly channel 21 through non-covalent interactions, and finally obtain water-soluble nanocrystals with high curcumin loading.

[0095] Example 2

[0096] Step 1: Weigh out soy protein isolate with a purity >90% and dissolve it in an aqueous solution to prepare an 8% soy protein isolate solution. After fully dissolving, place it in a refrigerator at 4°C overnight to fully hydrate and obtain the soy protein isolate solution.

[0097] Step 2: Dissolve rhamnolipin with a purity >95% in an aqueous solution to prepare an 8% rhamnolipin solution.

[0098] Step 3: Weigh curcumin with a purity >95% and dissolve it in an aqueous solution with pH=12. Sonicate for five minutes to dissolve all the curcumin and obtain a curcumin solution of 4.0 mg / mL.

[0099] Step 4: Before use, dilute the soy protein isolate solution and rhamnolipin solution separately and adjust their pH to 2. The final mass ratio of curcumin to soy protein isolate and rhamnolipin is 1:5:5.

[0100] Step 5: Inject curcumin solution, soy protein isolate solution, and rhamnolipid solution into the microfluidic device in Example 1 using a syringe pump. The flow rate for each solution is set to 0.8 m / s. The specific method is as follows:

[0101] The curcumin solution is fed into the first feed microchannel 11 through the first feed port 14. The curcumin solution is divided into two parts in the first feed microchannel 11 and enters through the half-circular arc respectively.

[0102] Soy protein isolate solution and rhamnolipin solution are introduced into the second feed microchannel 12 through the second feed port 15 and the third feed port 16, respectively; the soy protein isolate solution and rhamnolipin solution are first mixed in the second feed microchannel 12;

[0103] The mixed soy protein isolate solution and rhamnolipin solution were introduced into molecular assembly channel 13 together with curcumin solution and mixed for molecular assembly.

[0104] After molecular assembly, curcumin, soy protein isolate, and rhamnolipids continue to enter the nanocrystal assembly channel 21. Since the nanocrystal assembly channel 21 has a spiral reflux structure, the curcumin, soy protein isolate, and rhamnolipids continue to assemble into nanocrystals in the nanocrystal assembly channel 21 through non-covalent interactions, and finally obtain water-soluble nanocrystals with high curcumin loading.

[0105] Curcumin, protein, and lipid phases were introduced into inlets 1, 2, and 3 of the microfluidic chip, respectively, and the fluid flow rate was adjusted to 0.8 m / s. The solution was rapidly mixed and diffused in the microchannel, allowing curcumin to assemble with soy protein isolate and rhamnolipids into nanocrystals through non-covalent interactions.

[0106] Example 3

[0107] Step 1: Weigh out soy protein isolate with a purity >90% and dissolve it in an aqueous solution to prepare an 8% soy protein isolate solution. After fully dissolving, place it in a refrigerator at 4°C overnight to fully hydrate and obtain the soy protein isolate solution.

[0108] Step 2: Dissolve rhamnolipin with a purity >95% in an aqueous solution to prepare an 8% rhamnolipin solution.

[0109] Step 3: Weigh curcumin with a purity >95% and dissolve it in an aqueous solution with pH=12. Sonicate for five minutes to dissolve all the curcumin and obtain a curcumin solution of 4.0 mg / mL.

[0110] Step 4: Before use, dilute the soy protein isolate solution and rhamnolipin solution separately and adjust their pH to 2. The final mass ratio of curcumin to soy protein isolate and rhamnolipin is 1:2:8.

[0111] Step 5: Inject curcumin solution, soy protein isolate solution, and rhamnolipid solution into the microfluidic device in Example 1 using a syringe pump. The flow rate for each solution is set to 0.8 m / s. The specific method is as follows:

[0112] The curcumin solution is fed into the first feed microchannel 11 through the first feed port 14. The curcumin solution is divided into two parts in the first feed microchannel 11 and enters through the half-circular arc respectively.

[0113] Soy protein isolate solution and rhamnolipin solution are introduced into the second feed microchannel 12 through the second feed port 15 and the third feed port 16, respectively; the soy protein isolate solution and rhamnolipin solution are first mixed in the second feed microchannel 12;

[0114] The mixed soy protein isolate solution and rhamnolipin solution were introduced into molecular assembly channel 13 together with curcumin solution and mixed for molecular assembly.

[0115] After molecular assembly, curcumin, soy protein isolate, and rhamnolipids continue to enter the nanocrystal assembly channel 21. Since the nanocrystal assembly channel 21 has a spiral reflux structure, the curcumin, soy protein isolate, and rhamnolipids continue to assemble into nanocrystals in the nanocrystal assembly channel 21 through non-covalent interactions, and finally obtain water-soluble nanocrystals with high curcumin loading.

[0116] Comparative Example 1

[0117] The difference from Example 1 is that the microfluidic device used in Example 1 is not employed; instead, step 5 involves assembling curcumin with soy protein isolate and rhamnolipid through stirring. The specific method is as follows:

[0118] Step 1: Weigh out soy protein isolate with a purity >90% and dissolve it in an aqueous solution to prepare an 8% soy protein isolate solution. After fully dissolving, place it in a refrigerator at 4°C overnight to fully hydrate and obtain the soy protein isolate solution.

[0119] Step 2: Dissolve rhamnolipin with a purity >95% in an aqueous solution to prepare an 8% rhamnolipin solution.

[0120] Step 3: Weigh curcumin with a purity >95% and dissolve it in an aqueous solution with pH=12. Sonicate for five minutes to dissolve all the curcumin and obtain a curcumin solution of 4.0 mg / mL.

[0121] Step 4: Before use, dilute the soy protein isolate solution and rhamnolipin solution separately and adjust their pH to 2. The final mass ratio of curcumin to soy protein isolate and rhamnolipin is 1:8:2.

[0122] Step 5: Slowly add the rhamnolipin solution to the soy protein isolate solution and stir at 400 rpm for 3 minutes to obtain a soy protein isolate-rhamnolipin mixed solution. Then, slowly add the curcumin solution to the mixed solution and stir at room temperature in the dark for 30 minutes (400 rpm) to promote the assembly of curcumin with soy protein isolate and rhamnolipin into nanocrystals.

[0123] Comparative Example 2

[0124] The difference from Example 2 is that the microfluidic device used in Example 1 is not employed; that is, in step 5, curcumin is assembled with soy protein isolate and rhamnolipid through stirring. The specific method is as follows:

[0125] Step 1: Weigh out soy protein isolate with a purity >90% and dissolve it in an aqueous solution to prepare an 8% soy protein isolate solution. After fully dissolving, place it in a refrigerator at 4°C overnight to fully hydrate and obtain the soy protein isolate solution.

[0126] Step 2: Dissolve rhamnolipin with a purity >95% in an aqueous solution to prepare an 8% rhamnolipin solution.

[0127] Step 3: Weigh curcumin with a purity >95% and dissolve it in an aqueous solution with pH=12. Sonicate for five minutes to dissolve all the curcumin and obtain a curcumin solution of 4.0 mg / mL.

[0128] Step 4: Before use, dilute the soy protein isolate solution and rhamnolipin solution separately and adjust their pH to 2. The final mass ratio of curcumin to soy protein isolate and rhamnolipin is 1:5:5.

[0129] Step 5: Slowly add the rhamnolipin solution to the soy protein isolate solution and stir at 400 rpm for 3 minutes to obtain a soy protein isolate-rhamnolipin mixed solution. Then, slowly add the curcumin solution to the mixed solution and stir at room temperature in the dark for 30 minutes (400 rpm) to promote the assembly of curcumin with soy protein isolate and rhamnolipin into nanocrystals.

[0130] Comparative Example 3

[0131] The difference from Example 3 is that the microfluidic device used in Example 1 is not employed; instead, step 5 involves assembling curcumin with soy protein isolate and rhamnolipid through stirring. The specific method is as follows:

[0132] Step 1: Weigh out soy protein isolate with a purity >90% and dissolve it in an aqueous solution to prepare an 8% soy protein isolate solution. After fully dissolving, place it in a refrigerator at 4°C overnight to fully hydrate and obtain the soy protein isolate solution.

[0133] Step 2: Dissolve rhamnolipin with a purity >95% in an aqueous solution to prepare an 8% rhamnolipin solution.

[0134] Step 3: Weigh curcumin with a purity >95% and dissolve it in an aqueous solution with pH=12. Sonicate for five minutes to dissolve all the curcumin and obtain a curcumin solution of 4.0 mg / mL.

[0135] Step 4: Before use, dilute the soy protein isolate solution and rhamnolipin solution separately and adjust their pH to 2. The final mass ratio of curcumin to soy protein isolate and rhamnolipin is 1:2:8.

[0136] Step 5: Slowly add the rhamnolipin solution to the soy protein isolate solution and stir at 400 rpm for 3 minutes to obtain a soy protein isolate-rhamnolipin mixed solution. Then, slowly add the curcumin solution to the mixed solution and stir at room temperature in the dark for 30 minutes (400 rpm) to promote the assembly of curcumin with soy protein isolate and rhamnolipin into nanocrystals.

[0137] Comparative Example 4

[0138] The difference from Example 1 is that the microfluidic device used in Example 1 is not employed; instead, a different device is used. Figure 3 The microfluidic device shown in Figure A, Figure 3 The microfluidic device shown in Figure A differs from the microfluidic device in Example 1 in that the nanocrystal assembly channel 21 does not include the third arc 24 and the fourth arc 25, but the other structures are the same as those in Example 1.

[0139] The preparation method is the same as in Example 1.

[0140] Comparative Example 5

[0141] The difference from Example 1 is that the microfluidic device used in Example 1 is not employed; instead, a different device is used. Figure 3 The microfluidic device shown in B, Figure 3 The microfluidic device shown in B differs from the microfluidic device in Example 1 in that the radius of the third arc 24 in the nanocrystal assembly channel 21 is reduced to 2 cm, while the other structures are the same as those in Example 1.

[0142] The preparation method is the same as in Example 1.

[0143] Comparative Example 6

[0144] The difference from Example 1 is that the microfluidic device used in Example 1 is not employed; instead, a different device is used. Figure 3 The microfluidic device shown in C is... Figure 3 The microfluidic device shown in C differs from the microfluidic device in Example 1 in that the radius of the third arc 24 in the nanocrystal assembly channel 21 is increased to 8 cm, while the other structures are the same as those in Example 1.

[0145] The preparation method is the same as in Example 1.

[0146] Comparative Example 7

[0147] The microfluidic device described in Example 1 is used, but the difference from Example 1 is that the curcumin solution and soy protein isolate solution are mixed first, and then mixed with rhamnolipid solution. The specific method is as follows:

[0148] The rhamnolipin solution is fed into the first feed microchannel 11 through the first feed port 14. The rhamnolipin solution is divided into two parts in the first feed microchannel 11 and enters through the half-circular arc respectively.

[0149] Soy protein isolate solution and curcumin solution are introduced into the second feed microchannel 12 through the second feed port 15 and the third feed port 16, respectively; the soy protein isolate solution and curcumin solution are first mixed in the second feed microchannel 12;

[0150] The mixed soy protein isolate solution, curcumin solution, and rhamnolipin solution are introduced into molecular assembly channel 13 for mixing and molecular assembly.

[0151] The other steps are the same as in Example 1.

[0152] Test results and characterization

[0153] The nanocrystals prepared in Examples 1-3 and Comparative Examples 1-7 were tested using the following methods:

[0154] 1. The nanocrystals prepared in Examples 1-3 and Comparative Examples 1-7 were observed under an electron microscope, and the results are as follows: Figures 4-13 As shown.

[0155] 2. Particle size results of different nanoparticles

[0156] Test method: The prepared soybean protein isolate-rhamnolipin nanocrystal dispersions loaded with curcumin in different proportions were pretreated and measured by a nanoparticle size analyzer. The test results are shown in Table 1.

[0157] 3. Encapsulation efficiency and loading capacity of different nanoparticles

[0158] Test method: Take 2 mL of the prepared soy protein isolate-rhamnolipin nanocrystal dispersions loaded with curcumin at different ratios, centrifuge the dispersions at 10,000 rpm for 5 minutes to remove unencapsulated curcumin, take 100 μL of the supernatant, dilute, and measure the absorbance at 424 nm using a UV spectrophotometer. The encapsulation efficiency and loading capacity of the curcumin nanocrystals were calculated from the standard curve (R0). 2 >0.999). The calculation formula is as follows:

[0159] Encapsulation efficiency (%) = Curcumin content in nanocrystals / Total curcumin added × 100

[0160] Loading capacity (%) = Curcumin content in nanocrystals / Total weight of nanocrystals × 100

[0161] The measurement results are shown in Table 1.

[0162] 4. Solubility of different nanoparticles

[0163] Test Method: Freshly prepared soy protein isolate-rhamnolipin nanocrystal dispersions loaded with curcumin in different proportions were freeze-dried under vacuum to obtain nanocrystal powder. Excess of the above nanocrystal powder was weighed and dispersed in a sealed glass bottle containing 5 mL of distilled water (pH 6.8). These dispersions were incubated in a water bath (100 rpm, 25°C) until insoluble, and then collected. The dispersions were centrifuged at 10,000 rpm for 5 minutes to remove undissolved nanocrystal powder, and the supernatant was collected and filtered through a 0.45 μm microporous filter. The absorbance was measured at 424 nm using a UV-Vis spectrophotometer. The solubility of curcumin was calculated from a standard curve, and the results are shown in Table 1.

[0164] Figure 4 This is a scanning electron microscope image of the nanocrystals prepared in Example 1. Figure 5 This is a scanning electron microscope image of the nanocrystals from Example 2. Figure 6 Here is a scanning electron microscope image of the nanocrystals from Example 3. Figures 4-6 It can be seen that with the increase of rhamnolipin content, the particle size of the nanocrystals decreases significantly, and they exhibit distinct individual particle shapes. This is because curcumin alters the range and degree of attractive and repulsive interactions between the nanocrystals. Furthermore, the presence of a small amount of rhamnolipin reduces the interfacial tension between liquids and forms a three-dimensional rigid layer around the molecules, thereby preventing molecular aggregation and precipitation. With increasing rhamnolipin concentration, the curcumin complex nanocrystals exhibit stronger repulsive forces, contributing to the formation of a more uniform structure.

[0165] Figures 7-13 These are scanning electron microscope (SEM) images of the nanocrystals prepared in Comparative Examples 1–7. Figures 7-13It can be seen that the particle size of the nanocrystals in the comparative examples is significantly larger than that in the examples, and the particle size distribution is wider. The reason for this phenomenon in Comparative Examples 1-3 may be that the reaction is carried out in a larger container, the mixing process relies on magnetic stirring, and the reactant diffusion rate is slow, leading to instability in the nucleation and growth stages, thus generating larger and more widely distributed nanocrystals. The nanocrystal particle size distribution in Comparative Example 4 is uneven and irregular, possibly because the microfluidic chip lacks a helical reflux structure and complex flow path, resulting in lower fluid resistance and less shear force during crystal formation, leading to the formation of larger nanocrystals. The nanocrystal particle size in Comparative Examples 5-6 is slightly larger than that in Example 1, possibly due to differences in the helical reflux structure in the microfluidic chip. The nanocrystal particle size in Comparative Example 7 is the largest and has the widest distribution, possibly due to different molecular binding sequences. When the curcumin-soy protein isolate binary complex formed first binds to rhamnolipid, the binding sites become saturated, causing rhamnolipid to form a coating layer on the outer layer of the binary complex, thus forming larger nanocrystals.

[0166] Table 1. Particle size, encapsulation efficiency, loading capacity, and solubility of powder after rehydration of different nanocrystals

[0167]

[0168] Table 1 lists the particle size, encapsulation efficiency, loading capacity, and solubility of the nanocrystals prepared in Examples 1-3 and Comparative Examples 1-7. The experimental results show that the particle size of the nanocrystals significantly decreases with increasing rhamnolipin content. This is likely because rhamnolipin, as an amphiphilic lipid, can effectively reduce surface tension and promote the formation of small-diameter nanocrystals through steric hindrance. Example 2 showed the most outstanding performance, achieving the highest encapsulation efficiency and loading capacity. This is likely because the hydrogen bonding and hydrophobic interactions between soy protein isolate and rhamnolipin in Example 2 reached an optimal balance, resulting in a more stable nanostructure. The solubility of the nanocrystals also showed the same trend, as rhamnolipin, acting as a surfactant, reduced the surface tension of the system and improved solubility.

[0169] The nanocrystal encapsulation efficiency and loading capacity of Examples 1-3 were significantly higher than those of Comparative Examples 1-3, indicating that compared with conventional stirring assembly, the microfluidic device in Example 1 can better assemble curcumin with soy protein isolate and rhamnolipid into nanocrystals, achieving high loading of curcumin.

[0170] The nanocrystal encapsulation efficiency and loading capacity of Example 1 were significantly higher than those of Comparative Examples 4-6, indicating that compared to the microfluidic devices in Comparative Examples 4-6, the microfluidic device in Example 1 enabled curcumin to better assemble with soy protein isolate and rhamnolipid into nanocrystals, achieving high loading of curcumin. This may be because... Figure 1The nanocrystal assembly channel 21 incorporates a helical reflux structure, and its small arc radius allows the fluid to generate greater centrifugal force when passing through the curved section, resulting in stronger radial velocity changes and fluid turbulence. This not only breaks the laminar flow state of the fluid and enhances local convective mixing, but also allows for the formation of complex flow patterns through continuous arc design. This enables the components in the fluid to achieve effective mixing in a shorter time and smaller space, resulting in more uniform nanocrystal distribution, smaller particle size, and better encapsulation efficiency and loading capacity. In contrast, Figure 3 The nanocrystal assembly channel 21 in structure A does not contain the third arc 24 and the fourth arc 25, and therefore cannot form a spiral reflux structure. Figure 3 While structures B and C in the diagram also contain helical recirculation structures, the smaller radius of curvature in structure B leads to uneven fluid velocity distribution. In laminar flow, this uneven velocity distribution causes hydrodynamic instability that is often insufficient to promote effective mixing, thus affecting the mixing effect. In structure C, the larger radius of curvature reduces the centrifugal force generated when the fluid passes through the curved section, resulting in less eddy current generation. Fluid mixing relies primarily on laminar diffusion, leading to poorer mixing performance.

[0171] The nanocrystal encapsulation efficiency and loading capacity of Example 1 were significantly higher than those of Comparative Example 7, indicating that the mixing order of curcumin with soy protein isolate and rhamnolipin also affects the assembly effect of nanocrystals.

[0172] Therefore, whether the nanocrystal assembly channel 21 has a helical reflux structure, the size of the radius of the helical reflux structure, and the mixing order of curcumin with soy protein isolate and rhamnolipid will all affect the assembly effect of the microfluidic device on curcumin with soy protein isolate and rhamnolipid. This indicates that the microfluidic device and method in Example 1 have a good assembly effect on curcumin with soy protein isolate and rhamnolipid.

[0173] The present invention combines a nanocrystal preparation method based on microfluidic technology, which significantly improves the physicochemical properties of nanocrystals. The precise control capability of microfluidic technology at the microscale enables curcumin to bind precisely to the binding sites of soy protein isolate and rhamnolipid. Furthermore, curcumin is linked to soy protein isolate and rhamnolipid through hydrogen bonds and hydrophobic interactions, which is crucial for optimizing the physicochemical properties of nanocrystals.

[0174] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing water-soluble nanocrystals with high curcumin loading using a microfluidic device, characterized in that, The microfluidic device includes a molecular assembly section (1) and a nanocrystal assembly section (2). The molecular assembly section (1) includes a feed microchannel and a molecular assembly channel (13). The nanocrystal assembly section (2) includes at least one nanocrystal assembly channel (21) with a spiral reflux structure. The feed microchannel, the molecular assembly channel (13) and the nanocrystal assembly channel (21) are connected in sequence. The feed microchannel has a feed inlet and the nanocrystal assembly channel (21) has a discharge outlet (27). The method for preparing water-soluble nanocrystals with high curcumin loading using the microfluidic device includes the following steps: S1. Dissolve soy protein isolate in an aqueous solution and refrigerate to obtain a soy protein isolate solution; dissolve rhamnolipin in an aqueous solution to obtain a rhamnolipin solution; dissolve curcumin in an aqueous solution and sonicate to obtain a curcumin solution. S2. The soy protein isolate solution, rhamnolipin solution and curcumin solution are introduced into the feed microchannel through the feed inlet respectively. The soy protein isolate solution and rhamnolipin solution are mixed first, and then mixed together with curcumin solution in the molecular assembly channel (13) for molecular assembly. S3. Continue to enter the nanocrystal assembly channel (21) to assemble nanocrystals and obtain water-soluble nanocrystals with high curcumin load; Step S1 includes weighing soy protein isolate with a purity >90% and dissolving it in an aqueous solution. After complete dissolution, the solution is refrigerated at 0-4°C for 8-24 hours. The pH is adjusted to 2-3 using 0.1-2 mol / L HCl to obtain a soy protein isolate solution with a concentration of 7-9%. Rhamnolipin with a purity >95% is weighed and dissolved in an aqueous solution. The pH is adjusted to 2-3 using 0.1-2 mol / L HCl to obtain a rhamnolipin solution with a concentration of 7-9%. Curcumin with a purity >95% is weighed and dissolved in an aqueous solution with a pH of 11-12. The solution is then sonicated for 4-6 minutes to obtain a curcumin solution with a concentration of 3.0-5.0 mg / mL. The nanocrystal assembly channel (21) includes a first arc (22), a second arc (23), a third arc (24), a fourth arc (25), and a fifth arc (26) connected in sequence. The openings of the first arc (22), the third arc (24), and the fifth arc (26) face upwards, while the openings of the second arc (23) and the fourth arc (25) face downwards. The first arc (22), the second arc (23), and the fifth arc (26) all extend in a direction away from the molecular assembly segment (1), and the third arc (24) and the fourth arc (25) both extend in a direction close to the molecular assembly segment (1) to form a spiral reflux structure. The sum of the diameters of the third arc (24) and the fourth arc (25) is smaller than the diameter of the second arc (23). The radii of the first arc (22), the second arc (23), the third arc (24), the fourth arc (25), and the fifth arc (26) are 7~8cm, 12~13cm, 3~4cm, 3~4cm, and 7~8cm, respectively.

2. The method for preparing water-soluble nanocrystals with high curcumin loading using a microfluidic device according to claim 1, characterized in that, In step S1, the mass ratio of curcumin to soy protein isolate and rhamnolipin is 1:2~8:2~8.

3. The method for preparing water-soluble nanocrystals with high curcumin loading using a microfluidic device according to claim 1, characterized in that, The inner diameter of the feeding microchannel, molecular assembly channel (13), and nanocrystal assembly channel (21) is 0.5~1.2 mm, and the flow rates of the soybean protein isolate solution, rhamnolipin solution, and curcumin solution in the molecular assembly channel (13) and nanocrystal assembly channel (21) are 0.7~0.9 m / s.

4. The method for preparing water-soluble nanocrystals with high curcumin loading using a microfluidic device according to claim 1, characterized in that, The feeding microchannel includes a first feeding microchannel (11) and a second feeding microchannel (12). The feeding end of the first feeding microchannel (11) has a first feeding port (14), and the feeding end of the second feeding microchannel (12) has a second feeding port (15) and a third feeding port (16). The discharge end of the first feeding microchannel (11) and the discharge end of the second feeding microchannel (12) are both connected to the feeding end of the molecular assembly channel (13). In step S2, curcumin solution is introduced into the first feed microchannel (11) through the first feed port (14), and soy protein isolate solution and rhamnolipin solution are introduced into the second feed microchannel (12) through the second feed port (15) and the third feed port (16), respectively. The soy protein isolate solution and rhamnolipin solution are first mixed in the second feed microchannel (12), and then mixed together with the curcumin solution in the first feed microchannel (11) into the molecular assembly channel (13) for molecular assembly.

5. The method for preparing water-soluble nanocrystals with high curcumin loading using a microfluidic device according to claim 4, characterized in that, The first feeding microchannel (11) is circular or arc-shaped. The first feed port (14) and the molecular assembly channel (13) are respectively located at both ends of the first feeding microchannel (11). The second feeding microchannel (12) includes two feeding channels and one mixing channel. The two feeding channels and the mixing channel are set at an angle, and the mixing channel and the molecular assembly channel (13) are set in a straight line.

6. The method for preparing water-soluble nanocrystals with high curcumin loading using a microfluidic device according to claim 1, characterized in that, The number of nanocrystal assembly channels (21) is 2 to 6, and the 2 to 6 nanocrystal assembly channels (21) are connected in sequence to form the nanocrystal assembly segment (2).

7. A water-soluble nanocrystal with high curcumin loading prepared by the method according to any one of claims 1 to 6, characterized in that, The nanocrystals have a particle size of 50~160nm, an encapsulation rate of curcumin greater than 90%, and a loading capacity of curcumin greater than 7%.

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