Lycopene carrier microspheres and preparation method and application thereof

Through membrane emulsification technology and microfluidic control technology, combined with the use of specific components, the problems of low loading, uneven particle size and easy adhesion of lycopene carrier microspheres are solved, and the microsphere morphology with uniform particle size, good dispersion and no adhesion are achieved, which improves the coating performance and use performance of the carrier.

CN118948778BActive Publication Date: 2025-03-28WUHAN STARS MODERN BIO-ENG CO LTD
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Patent Information

Application Number
CN202411077671.8
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2024-08-06
Publication Date
2025-03-28
Estimated Expiration
2044-08-06

AI Technical Summary

Technical Problem

The existing lycopene carrier microsphere technology has problems such as low loading, uneven particle size distribution and easy adhesion, which affects its application effect.

Method used

The membrane emulsification process is combined with microfluidic control technology, and by adding specific components such as hydroxyproline, polycaprolactone, disaccharide and quaternary ammonium salts to the oil and aqueous phases, the interface inhibits the membrane and intermolecular embedding, prevents the fusion and adhesion of the droplets, and regulates the microsphere morphology through solvent evaporation.

Benefits of technology

The uniform particle size distribution, good dispersion and non-adhesion morphology of the lycopene carrier microspheres were achieved, and the coating and use performance of the carrier were improved.

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Abstract

The present application relates to the technical field of lycopene microspheres, and specifically discloses a lycopene carrier microsphere and a preparation method thereof. A preparation method of lycopene carrier microspheres, comprising the following steps: 1) lycopene, hydroxyproline, polycaprolactone, and a solvent are mixed evenly to obtain an oil phase; 2) water and an emulsifier are mixed evenly to obtain an aqueous phase; 3) the oil phase is evenly dispersed in the aqueous phase using a membrane emulsification process to obtain a pre-liquid, and then the pre-liquid is subjected to solvent evaporation, and after the solvent is completely evaporated, the pre-liquid is filtered, washed, and dried to obtain the pre-liquid. The lycopene carrier microspheres prepared in the present application have the advantages of uniform particle size distribution and low adhesion.
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Description

Technical Field

[0001] The present application relates to the technical field of lycopene microspheres, and more specifically, to a lycopene carrier microsphere and a preparation method and application thereof. Background Art

[0002] Lycopene is a fat-soluble unsaturated hydrocarbon, a type of carotenoid, with antioxidant and immunity-enhancing functions, and is widely used in medicines, health products, cosmetics, and food additives. Lycopene molecules contain 11 conjugated double bonds and two non-conjugated double bonds, and are chemically very unstable. Without the protection of other media, cis-trans isomerization and oxidative degradation are likely to occur, affecting its bioavailability.

[0003] In the human body, cis-configuration lycopene is more easily absorbed than trans-configuration lycopene. Factors that affect the stability of lycopene include light, heat, oxygen, acid, metal ions, oxidants and antioxidants. Therefore, lycopene needs to be protected by a medium to improve stability and bioavailability. In addition, lycopene is poorly soluble in water, and this water insolubility and instability also greatly limits its application.

[0004] Microcapsule technology and microsphere technology are encapsulation technologies that use natural or synthetic polymer materials to encapsulate the target object to form a sealed capsule wall and small particles with good fluidity. It can protect the core material from the influence of the external biochemical environment, significantly improve the existence state of the core material, provide stability and water solubility, and achieve controlled and sustained release of the core material. However, due to the chemical properties of lycopene, the lycopene loading of traditional microcapsule and microsphere technology is low, and the particle size distribution of the capsule is also poor, which is easy to produce adhesion and affects the use effect. Summary of the invention

[0005] In order to further improve the coating performance and use performance of lycopene carriers, the present application provides a lycopene carrier microsphere and a preparation method and application thereof.

[0006] In a first aspect, the present application provides a method for preparing lycopene carrier microspheres, using the following technical solution:

[0007] A method for preparing lycopene carrier microspheres comprises the following steps:

[0008] 1) uniformly mixing lycopene, hydroxyproline, polycaprolactone and a solvent to prepare an oil phase;

[0009] 2) uniformly mixing water and an emulsifier to obtain an aqueous phase;

[0010] 3) The oil phase is uniformly dispersed in the water phase by a membrane emulsification process to prepare a pre-liquid, and then the solvent of the pre-liquid is evaporated. After the solvent is completely evaporated, the pre-liquid is filtered, washed, and dried.

[0011] Preferably, the step 3) further includes at least one of the following technical features:

[0012] 31) The membrane emulsification process conditions are as follows: the membrane emulsification process conditions of the water phase are as follows: the flow rate of the water phase is 1200-1500 mL / min, the membrane specification is a membrane sheet with a membrane pore size of 15 μm, and the transmembrane pressure is 0.55-0.7 MPa;

[0013] 32) Disaccharide and quaternary ammonium salt are added to the aqueous phase by microfluidics, wherein the fitting equation of the change trend of the concentration of disaccharide in the aqueous phase over time is: y1 = -0.15 + 0.028m + 0.0007m 2 , where y1 represents the concentration of disaccharide in the aqueous phase, in wt%, and m represents time, in min, with the interval range of m being [0,60]. The fitting equation for the change trend of the concentration of quaternary ammonium salt in the aqueous phase over time is: y2 = 0.12 + 0.037n - 0.00033n 2 , where y2 represents the concentration of quaternary ammonium salt in the aqueous phase in wt%, n represents time in min, and the interval range of n is [0,60].

[0014] Preferably, in said 32), the disaccharide is one or more of maltose, lactose and sucrose.

[0015] Preferably, in said 32), the disaccharide consists of maltose and lactose in a mass ratio of 1:0.35.

[0016] Preferably, in said 32), the quaternary ammonium salt is one or more of tetrabutylammonium chloride, tetrapropylammonium chloride, tetraethylammonium chloride and tetramethylammonium chloride.

[0017] Preferably, in said 32), the quaternary ammonium salt is composed of tetrabutylammonium chloride and tetramethylammonium chloride in a molar ratio of 1:0.15.

[0018] Preferably, the step 1) further includes at least one of the following technical features:

[0019] 11) In the oil phase, the mass of lycopene, hydroxyproline, polycaprolactone and solvent is (0.65-1):(0.05-0.1):(5-8):100;

[0020] 12) The solvent is one of toluene, acetone, dichloromethane and chloroform;

[0021] 13) The number average molecular weight of the polycaprolactone is 10000-20000 g / mol.

[0022] Preferably, the step 1) further includes at least one of the following technical features:

[0023] 21) In the aqueous phase, the mass ratio of water to emulsifier is 1:(0.02-0.03);

[0024] 22) The emulsifier is one of polyvinyl alcohol, polyethylene glycol, and sucrose ester.

[0025] In a second aspect, the present application provides a lycopene carrier microsphere, which is prepared by the above-mentioned preparation method.

[0026] In a third aspect, the present application provides an application of lycopene carrier microspheres, wherein the microspheres prepared by the above preparation method or the microspheres described in claim 9 are used to prepare medicines and cosmetics.

[0027] In summary, this application has the following beneficial effects:

[0028] 1. The present application adopts a membrane emulsification process to form a uniformly dispersed emulsion in the water phase, and finally obtains carrier microspheres with uniform particle size and not easy to adhere. Wherein, the oil phase is composed of lycopene, hydroxyproline, polycaprolactone and solvent. During the membrane emulsification process, hydroxyproline is distributed on the surface of the oil phase droplets to form an interfacial inhibition film, which hinders the fusion and adhesion between adjacent droplets. In addition, disaccharides and quaternary ammonium salts are also added to the water phase. Disaccharides and quaternary ammonium salts can form intermolecular embedding in the interfacial inhibition film, and the barrier effect is further enhanced by the effects of three-dimensional hydrogen bonds, steric hindrance, van der Waals forces, etc., reducing the re-fusion and adhesion between adjacent droplets. In addition, during the solvent evaporation process, the volatilization rate of the solvent can also be regulated to avoid the instability of the microsphere morphology caused by the excessively fast solvent volatilization rate, thereby improving the morphological uniformity and dispersibility of the carrier microspheres.

[0029] 2. In the present application, microfluidics is preferably used to regulate the addition rate of disaccharides and quaternary ammonium salts in the aqueous phase, so that the concentration increase rate of the disaccharides in the aqueous phase is first slow and then fast, and the concentration increase of the quaternary ammonium salt in the aqueous phase is first fast and then slow. The purpose of this is that in the early stage of membrane emulsification, the quaternary ammonium salt plays a dominant role, which can reduce the oil-water interfacial tension and is conducive to the formation of initial droplets. In the middle and late stages of membrane emulsification, the disaccharides play a dominant role. As the concentration of disaccharides in the aqueous phase system continues to increase, the disaccharide molecules can inhibit the formation of adsorption outside the membrane at the interface, play interface effects such as isolation and peeling, and further reduce the adhesion between adjacent droplets.

[0030] 3. The lycopene carrier microspheres prepared by the preparation method of the present application have a relatively uniform particle size distribution and no adverse morphology such as adhesion. In addition, the solvent used in the oil phase can be reused by adopting the membrane emulsification solvent volatilization process. Moreover, the solvent will not remain in the microsphere carrier, which is more environmentally friendly and more suitable for the preparation of medicines and cosmetics. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 It is a SEM schematic diagram of the lycopene carrier microspheres of Examples 1-3 of the present application.

[0032] Figure 2 It is a SEM schematic diagram of the lycopene carrier microspheres of Examples 4-6 of the present application.

[0033] Figure 3 It is a SEM schematic diagram of the lycopene carrier microspheres of Comparative Example 1 of the present application. DETAILED DESCRIPTION

[0034] The present application is further described in detail below with reference to the embodiments.

[0035] Unless otherwise specified, the raw materials used in the examples and comparative examples of the present application are all commercially available.

[0036] Example 1

[0037] The preparation method of lycopene carrier microspheres of this embodiment comprises the following steps:

[0038] 1) Add 100 g of lycopene, 10 g of hydroxyproline, 800 g of polycaprolactone and 10 L of solvent into a stirred tank, heat to 40° C., mix uniformly by ultrasonication to obtain an oil phase, and store the oil phase in an oil phase tank;

[0039] 2) mixing water and emulsifier in a mass ratio of 1:0.03 to obtain a water phase, and storing the water phase in a water phase tank;

[0040] 3) A membrane emulsification process is used to apply pressure to the oil phase through nitrogen, so that the oil phase is evenly dispersed in the water phase through the membrane to prepare a pre-liquid. The flow rate of the water phase is 1200 mL / min, and the water phase is kept circulating between the membrane emulsification device and the water phase tank. The membrane specification is a membrane with a pore size of 15 μm, and the transmembrane pressure is 0.7 MPa. After the oil phase has completely entered the water phase, the pre-liquid is magnetically stirred at room temperature to evaporate the solvent. After the solvent has evaporated completely, it is filtered, washed three times by centrifugation with deionized water, and then placed in a vacuum freeze dryer for drying.

[0041] The solvent is toluene, the emulsifier is polyethylene glycol, and the number average molecular weight of polycaprolactone is 20000 g / mol.

[0042] The lycopene carrier microspheres of this embodiment are prepared by the above-mentioned preparation method.

[0043] Example 2

[0044] The preparation method of lycopene carrier microspheres of this embodiment comprises the following steps:

[0045] 1) Add 65 g of lycopene, 5 g of hydroxyproline, 500 g of polycaprolactone, and 10 L of solvent into a stirred tank, heat to 40° C., and mix them evenly by ultrasonication to obtain an oil phase, which is then stored in an oil phase tank;

[0046] 2) Mix water and emulsifier in a mass ratio of 1:0.02 to obtain a water phase, and store the water phase in a water phase tank;

[0047] 3) Using membrane emulsification technology, nitrogen is used to apply pressure to the oil phase, so that the oil phase is evenly dispersed in the water phase through the membrane to prepare a pre-liquid. The flow rate of the water phase is 1500mL / min, and the water phase keeps circulating between the membrane emulsification device and the water phase tank. The membrane specification is a membrane with a pore size of 15μm, and the transmembrane pressure is 0.55MPa; PLC is used to control a dual-channel peristaltic pump, and disaccharides and quaternary ammonium salts are added to the water phase through microfluidics. Disaccharides and quaternary ammonium salts are both water-saturated solutions. Among them, the fitting equation for the change trend of the concentration of disaccharides in the water phase over time is: y1 = -0.15 + 0.028m + 0.0007m 2 , where y1 represents the concentration of disaccharide in the aqueous phase, in wt%, and m represents time, in min, with the interval range of m being [0,60]. The fitting equation for the change trend of the concentration of quaternary ammonium salt in the aqueous phase over time is: y2 = 0.12 + 0.037n - 0.00033n 2 , where y2 represents the concentration of quaternary ammonium salt in the aqueous phase in wt%, n represents time in min, and the interval range of n is [0,60].

[0048] After the oil phase has completely entered the water phase, the pre-liquid is magnetically stirred at room temperature to evaporate the solvent. After the solvent is completely evaporated, it is filtered, washed three times by centrifugation with deionized water, and then placed in a vacuum freeze dryer for drying.

[0049] The solvent is dichloromethane, the emulsifier is polyethylene glycol, the number average molecular weight of polycaprolactone is 10000 g / mol, the disaccharide is lactose, and the quaternary ammonium salt is tetrabutylammonium chloride.

[0050] The lycopene carrier microspheres of this embodiment are prepared by the above-mentioned preparation method.

[0051] Example 3

[0052] The preparation method of lycopene carrier microspheres of this embodiment comprises the following steps:

[0053] 1) Add 85 g of lycopene, 7.5 g of hydroxyproline, 700 g of polycaprolactone, and 10 L of solvent into a stirred tank, heat to 40° C., and mix uniformly by ultrasonication to obtain an oil phase, which is then stored in an oil phase tank;

[0054] 2) Mix water and emulsifier in a mass ratio of 1:0.03 to obtain a water phase, and store the water phase in a water phase tank;

[0055] 3) Using membrane emulsification technology, nitrogen is used to apply pressure to the oil phase, so that the oil phase is evenly dispersed in the water phase through the membrane to prepare a pre-liquid. The flow rate of the water phase is 1200mL / min, and the water phase keeps circulating between the membrane emulsification device and the water phase tank. The membrane specification is a membrane with a pore size of 15μm, and the transmembrane pressure is 0.65MPa; PLC is used to control a dual-channel peristaltic pump, and disaccharides and quaternary ammonium salts are added to the water phase through microfluidics. Disaccharides and quaternary ammonium salts are both water-saturated solutions. Among them, the fitting equation for the change trend of the concentration of disaccharides in the water phase over time is: y1 = -0.15 + 0.028m + 0.0007m 2 , where y1 represents the concentration of disaccharide in the aqueous phase, in wt%, and m represents time, in min, with the interval range of m being [0,60]. The fitting equation for the change trend of the concentration of quaternary ammonium salt in the aqueous phase over time is: y2 = 0.12 + 0.037n - 0.00033n 2 , where y2 represents the concentration of quaternary ammonium salt in the aqueous phase in wt%, n represents time in min, and the interval range of n is [0,60].

[0056] After the oil phase has completely entered the water phase, the pre-liquid is magnetically stirred at room temperature to evaporate the solvent. After the solvent is completely evaporated, it is filtered, washed three times by centrifugation with deionized water, and then placed in a vacuum freeze dryer for drying.

[0057] The solvent is dichloromethane. The emulsifier is polyethylene glycol. The number average molecular weight of polycaprolactone is 10000 g / mol. The disaccharide is composed of maltose and lactose in a mass ratio of 1:0.35. The quaternary ammonium salt is composed of tetrabutylammonium chloride and tetramethylammonium chloride in a molar ratio of 1:0.15.

[0058] The lycopene carrier microspheres of this embodiment are prepared by the above-mentioned preparation method.

[0059] Example 4

[0060] The preparation method of lycopene carrier microspheres of this embodiment comprises the following steps:

[0061] 1) Add 85 g of lycopene, 7.5 g of hydroxyproline, 700 g of polycaprolactone, and 10 L of solvent into a stirred tank, heat to 40° C., and mix uniformly by ultrasonication to obtain an oil phase, which is then stored in an oil phase tank;

[0062] 2) Mix water and emulsifier in a mass ratio of 1:0.03 to obtain a water phase, and store the water phase in a water phase tank;

[0063] 3) Using membrane emulsification technology, nitrogen is used to apply pressure to the oil phase, so that the oil phase is evenly dispersed in the water phase through the membrane to prepare a pre-liquid. The flow rate of the water phase is 1200mL / min, and the water phase is kept circulating between the membrane emulsification device and the water phase tank. The membrane specification is a membrane with a pore size of 15μm, and the transmembrane pressure is 0.65MPa; PLC is used to control a dual-channel peristaltic pump, and disaccharides and triethylamine are added to the water phase through microfluidics. The disaccharide is a water-saturated solution. Among them, the fitting equation for the change trend of the concentration of disaccharides in the water phase over time is: y1 = -0.15 + 0.028m + 0.0007m 2 , where y1 represents the concentration of disaccharide in the aqueous phase, in wt%, and m represents time, in min, with the interval range of m being [0,60]. The fitting equation for the change trend of the concentration of quaternary ammonium salt in the aqueous phase over time is: y2 = 0.12 + 0.037n - 0.00033n 2 , where y2 represents the concentration of quaternary ammonium salt in the aqueous phase in wt%, n represents time in min, and the interval range of n is [0,60].

[0064] After the oil phase completely enters the water phase, the pre-liquid is magnetically stirred at room temperature to evaporate the solvent. After the solvent is completely evaporated, it is filtered, washed three times by centrifugation with deionized water, and then placed in a vacuum freeze dryer for drying.

[0065] The solvent is dichloromethane, the emulsifier is polyethylene glycol, the number average molecular weight of polycaprolactone is 10000 g / mol, and the disaccharide is composed of maltose and lactose in a mass ratio of 1:0.35.

[0066] The lycopene carrier microspheres of this embodiment are prepared by the above-mentioned preparation method.

[0067] Example 5

[0068] The preparation method of lycopene carrier microspheres of this embodiment comprises the following steps:

[0069] 1) Add 85 g of lycopene, 7.5 g of hydroxyproline, 700 g of polycaprolactone, and 10 L of solvent into a stirred tank, heat to 40° C., and mix uniformly by ultrasonication to obtain an oil phase, which is then stored in an oil phase tank;

[0070] 2) Mix water and emulsifier in a mass ratio of 1:0.03 to obtain a water phase, and store the water phase in a water phase tank;

[0071] 3) Using membrane emulsification technology, applying pressure to the oil phase through nitrogen, the oil phase is evenly dispersed in the water phase through the membrane to prepare a pre-liquid, the flow rate of the water phase is 1200mL / min, and the water phase keeps circulating between the membrane emulsification device and the water phase tank, the membrane specification is a membrane with a pore size of 15μm, and the transmembrane pressure is 0.65MPa; using PLC to control a dual-channel peristaltic pump, sodium alginate and quaternary ammonium salt are added to the water phase through microfluidics, sodium alginate is a 1.5% aqueous solution, and quaternary ammonium salt is a water-saturated solution. Among them, the fitting equation for the change trend of the concentration of disaccharides in the water phase over time is: y1 = -0.15 + 0.028m + 0.0007m 2 , where y1 represents the concentration of disaccharide in the aqueous phase, in wt%, and m represents time, in min, with the interval range of m being [0,60]. The fitting equation for the change trend of the concentration of quaternary ammonium salt in the aqueous phase over time is: y2 = 0.12 + 0.037n - 0.00033n 2 , where y2 represents the concentration of quaternary ammonium salt in the aqueous phase in wt%, n represents time in min, and the interval range of n is [0,60].

[0072] After the oil phase completely enters the water phase, the pre-liquid is magnetically stirred at room temperature to evaporate the solvent. After the solvent is completely evaporated, it is filtered, washed three times by centrifugation with deionized water, and then placed in a vacuum freeze dryer for drying.

[0073] The solvent is dichloromethane, the emulsifier is polyethylene glycol, the number average molecular weight of polycaprolactone is 10000 g / mol, and the quaternary ammonium salt is composed of tetrabutylammonium chloride and tetramethylammonium chloride in a molar ratio of 1:0.15.

[0074] The lycopene carrier microspheres of this embodiment are prepared by the above-mentioned preparation method.

[0075] Example 6

[0076] The preparation method of lycopene carrier microspheres of this embodiment comprises the following steps:

[0077] 1) Add 65 g of lycopene, 5 g of hydroxyproline, 500 g of polycaprolactone, and 10 L of solvent into a stirred tank, heat to 40° C., and mix them evenly by ultrasonication to obtain an oil phase, which is then stored in an oil phase tank;

[0078] 2) Mix water and emulsifier in a mass ratio of 1:0.02 to obtain a water phase, and store the water phase in a water phase tank;

[0079] 3) adopting membrane emulsification process, applying pressure to the oil phase by nitrogen, making the oil phase uniformly dispersed in the water phase through the membrane to prepare the pre-liquid, the flow rate of the water phase is 1500mL / min, and the water phase keeps circulating between the membrane emulsification device and the water phase tank, the membrane specification is a membrane with a membrane pore size of 15μm, and the transmembrane pressure is 0.55MPa; adopting PLC to control the dual-channel peristaltic pump, adding disaccharides and quaternary ammonium salts to the water phase by microfluidic mode, and the disaccharides and quaternary ammonium salts are both water-saturated solutions. Wherein, the concentration of disaccharides in the water phase is 3.5wt%; the concentration of the quaternary ammonium salt in the water phase is 1.15wt%.

[0080] After the oil phase completely enters the water phase, the pre-liquid is magnetically stirred at room temperature to evaporate the solvent. After the solvent is completely evaporated, it is filtered, washed three times by centrifugation with deionized water, and then placed in a vacuum freeze dryer for drying.

[0081] The solvent is dichloromethane, the emulsifier is polyethylene glycol, the number average molecular weight of polycaprolactone is 10000 g / mol, the disaccharide is lactose, and the quaternary ammonium salt is tetrabutylammonium chloride.

[0082] The lycopene carrier microspheres of this embodiment are prepared by the above-mentioned preparation method.

[0083] Comparative Example 1

[0084] The preparation method of the lycopene carrier microspheres of this comparative example comprises the following steps:

[0085] 1) Add 10 g of lycopene, 80 g of polycaprolactone and 1000 mL of solvent into a stirred tank, heat to 40° C., mix uniformly by ultrasonication to obtain an oil phase, and store the oil phase in an oil phase tank;

[0086] 2) Mix water and emulsifier in a mass ratio of 1:0.03 to obtain a water phase, and store the water phase in a water phase tank;

[0087] 3) A membrane emulsification process is used to apply pressure to the oil phase through nitrogen, so that the oil phase is evenly dispersed in the water phase through the membrane to prepare a pre-liquid. The flow rate of the water phase is 1200 mL / min, and the water phase is kept circulating between the membrane emulsification device and the water phase tank. The membrane specification is a membrane with a pore size of 15 μm, and the transmembrane pressure is 0.7 MPa. After the oil phase completely enters the water phase, the pre-liquid is magnetically stirred at room temperature to evaporate the solvent. After the solvent is completely evaporated, it is filtered, washed three times by centrifugation with deionized water, and then placed in a vacuum freeze dryer for drying.

[0088] The solvent is toluene, the emulsifier is polyethylene glycol, and the number average molecular weight of polycaprolactone is 20000 g / mol.

[0089] The lycopene carrier microspheres of this comparative example were prepared by the above-mentioned preparation method.

[0090] Performance testing

[0091] The lycopene carrier microspheres of Examples 1-6 and Comparative Example 1 were tested by scanning electron microscopy. The test results are as follows: Figure 1-3 shown.

[0092] Analyze Examples 1-3, Examples 4-6, and Comparative Example 1 and combine Figure 1-3 It can be seen that when disaccharides and quaternary ammonium salts are added to the aqueous phase within a certain period of time using microfluidic technology, the number of emulsion droplets in the aqueous phase is relatively small at the beginning of the membrane emulsification process, and the dispersion uniformity is good. Adhesion does not occur at this time, and the content of disaccharides and quaternary ammonium salts in the aqueous phase is also relatively low. With the continuous circulation of the aqueous phase, the number of emulsion droplets in the aqueous phase gradually increases, and adjacent droplets are prone to collision and fusion. At this time, disaccharides and quaternary ammonium salts play their respective roles, inhibiting the fusion and adhesion of adjacent droplets, and obtaining carrier microspheres with a good dispersion state.

[0093] When Example 4 and Example 5 used triethylamine and sodium alginate as the inhibitor components, the adhesion of the microspheres was serious, which may be caused by the destruction of the stability of the system. The examples use a fixed concentration. In the early stage of membrane emulsification, after the emulsion droplets enter the water phase, the large droplets will fuse more easily, resulting in the generation of droplets with too large particle size. The emulsion in Comparative Example 1 has very serious adhesion, fused with each other, and has a poor morphology.

[0094] It can be seen that by combining membrane emulsification and microfluidics technology and cooperating with multiple components, lycopene carrier microspheres with good dispersibility, uniform particle size and good morphology can be obtained.

[0095] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed. However, as long as it is within the scope of the claims of the present application, it shall be protected by the patent law.

Claims

1. A method for preparing lycopene carrier microspheres, characterized in that: The steps include: 1) uniformly mixing lycopene, hydroxyproline, polycaprolactone and a solvent to prepare an oil phase; 2) uniformly mixing water and an emulsifier to obtain an aqueous phase; 3) The oil phase is uniformly dispersed in the water phase by a membrane emulsification process to obtain a pre-liquid, and then the pre-liquid is subjected to solvent evaporation, and after the solvent is completely evaporated, the pre-liquid is filtered, washed, and dried to obtain the pre-liquid; the membrane emulsification process conditions are: the flow rate of the water phase is 1200-1500mL / min, the membrane specification is a membrane sheet with a membrane pore size of 15μm, and the transmembrane pressure is 0.55-0.7MPa; disaccharides and quaternary ammonium salts are added to the water phase by microfluidics, wherein the fitting equation for the change trend of the concentration of disaccharides in the water phase over time is: y1=-0.15+0.028m+0.0007m 2 , where y1 represents the concentration of disaccharide in the aqueous phase, in wt%, and m represents time, in min, with the interval range of m being [0,60]. The fitting equation for the change trend of the concentration of quaternary ammonium salt in the aqueous phase over time is: y2 = 0.12 + 0.037n - 0.00033n 2 , where y2 represents the concentration of quaternary ammonium salt in the aqueous phase in wt%, n represents time in min, and the interval range of n is [0,60].

2. The method for preparing lycopene carrier microspheres according to claim 1, characterized in that: In the step 3), the disaccharide is one or more of maltose, lactose and sucrose.

3. The method for preparing lycopene carrier microspheres according to claim 2, characterized in that: In the step 3), the disaccharide is composed of maltose and lactose in a mass ratio of 1:0.

35.

4. The method for preparing lycopene carrier microspheres according to claim 1, characterized in that: In the step 3), the quaternary ammonium salt is one or more of tetrabutylammonium chloride, tetrapropylammonium chloride, tetraethylammonium chloride and tetramethylammonium chloride.

5. The method for preparing lycopene carrier microspheres according to claim 4, characterized in that: In the step 3), the quaternary ammonium salt is composed of tetrabutylammonium chloride and tetramethylammonium chloride in a molar ratio of 1:0.

15.

6. The method for preparing lycopene carrier microspheres according to claim 5, characterized in that: In the step 1), at least one of the following technical features is also included: 11) In the oil phase, the mass of lycopene, hydroxyproline, polycaprolactone and solvent is (0.65-1):(0.05-0.1):(5-8):100; 12) The solvent is one of toluene, acetone, dichloromethane and chloroform; 13) The number average molecular weight of the polycaprolactone is 10000-20000 g / mol.

7. The method for preparing lycopene carrier microspheres according to claim 1, characterized in that: In the step 1), at least one of the following technical features is also included: 21) In the aqueous phase, the mass ratio of water to emulsifier is 1:(0.02-0.03); 22) The emulsifier is one of polyvinyl alcohol, polyethylene glycol, and sucrose ester.

8. A lycopene carrier microsphere, characterized in that: The method is prepared by any one of claims 1 to 7.

9. An application of lycopene carrier microspheres, characterized in that: The microspheres prepared by the preparation method according to any one of claims 1 to 7 or the microspheres according to claim 8 are used to prepare medicines and cosmetics.

Citation Information

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