Flavone particle-based emulsion system as well as preparation method and application thereof

Abstract

The invention discloses a flavone particle-based emulsion system as well as a preparation method and application thereof, and relates to the field of emulsions. According to the invention, an anti-solvent phase is optimized, an efficient mixing system is constructed by adopting an anti-solvent collision technology, and the dynamic solubility of the system is accurately regulated and controlled, so that flavone is guided to orderly generate self-assembly, and the flavone nanoparticle emulsifier of which the particle size is accurately controlled by the solvent collision temperature is formed; the flavone nanoparticles are used as an emulsifier, so that the construction of an antioxidant oil-water interface is realized, the defect that a large amount of synthetic surfactants are needed in the prior art is avoided, and the bioavailability and oxidation stability of functional easily-oxidized grease are effectively improved; and a new solution is provided for high-efficiency delivery of different types of easy-to-oxidize functional grease and slightly-soluble flavonoids.

Description

Technical Field

[0001] This invention relates to the field of emulsions, and more specifically, to a flavonoid particle-based emulsion system, its preparation method, and its application. Background Technology

[0002] Flavonoids, as natural polyphenolic active ingredients widely found in the plant kingdom, possess excellent antioxidant, anti-inflammatory, anti-tumor, and cardiovascular protective activities, making them highly valuable in the food, pharmaceutical, and health product fields and a key area of ​​current natural product research. However, flavonoids generally suffer from poor water solubility (usually slightly soluble or sparingly soluble in water), resulting in poor dispersibility in water-based systems. This not only hinders their effective absorption by the human body but also severely limits their application in mainstream product forms such as oral liquids, beverages, and water-based gels, seriously restricting their bioavailability and industrialization process.

[0003] Meanwhile, functional oils (such as fish oil, algal oil, and krill oil) are important sources of active ingredients such as Omega-3 polyunsaturated fatty acids (such as EPA and DHA) and phospholipids, playing key physiological roles in regulating blood lipids, protecting the nervous system, and improving immune function. They are also core functional raw materials in the food and pharmaceutical fields. However, these oils are rich in unsaturated double bonds and are chemically unstable. During processing, storage, and application, they are prone to rancidity and flavor deterioration due to oxidation. This not only destroys their inherent physiological activity but also produces oxidation products such as aldehydes and ketones that are harmful to the human body, leading to decreased product stability, shortened shelf life, and significantly reduced bioavailability. This problem has become a major bottleneck in the industrial application of functional oils.

[0004] Currently, emulsification technology is a common delivery strategy to solve the above-mentioned problems of dispersibility of insoluble / slightly soluble components and stability of easily oxidized components. Its core is to disperse insoluble or slightly soluble components (such as flavonoids and functional oils) in one of the bulk phases through external forces (such as shearing, impact, and turbulence) to form a thermodynamically metastable emulsion system, thereby improving the dispersibility and applicability of the components. However, traditional emulsification technology still has significant limitations in practical applications: to achieve long-term stability of emulsions, a large amount of synthetic surfactants (such as sodium lauryl sulfate, Tween series, etc.) are often added. These surfactants may not only cause potential health risks (such as irritating the gastrointestinal tract and affecting the balance of intestinal flora), but may also change the taste, texture and flavor of the product (such as producing astringency and greasiness), which does not meet the current consumer demand for "natural and safe" products. More importantly, the main function of traditional surfactants is to reduce interfacial tension to maintain the dispersion state. They cannot effectively isolate oxygen from easily oxidized components (such as unsaturated fatty acids in functional oils), and are difficult to inhibit oxidative rancidity reactions, resulting in insufficient oxidative stability of the emulsion system. Therefore, the problem of oxidative deterioration of functional oils cannot be fundamentally solved.

[0005] Therefore, developing a novel delivery system that combines high-efficiency dispersion, excellent oxidative stability, safety, and low cost is of great practical significance and urgent need for breaking through the application bottlenecks of flavonoids and functional oils and enhancing their industrial value in food, medicine, and health products.

[0006] In view of this, the present invention is proposed. Summary of the Invention

[0007] The purpose of this invention is to provide a flavonoid particulate-based emulsion system and its preparation method.

[0008] This invention is implemented as follows: In a first aspect, embodiments of the present invention provide an emulsion, wherein the raw materials, by volume percentage, comprise: 15%~47.5% solvent phase, 15%~47.5% antisolvent phase, and 5%~70% oil phase; The solvent phase is obtained by dissolving flavonoids in water at a first set temperature; the antisolvent phase is water or an ice-water mixture at a second set temperature, wherein the first set temperature is greater than the second set temperature.

[0009] Secondly, embodiments of the present invention provide a method for preparing an emulsion as described in the foregoing embodiments, which includes preparation using the raw materials described in the foregoing embodiments.

[0010] Thirdly, the embodiments of the present invention provide the application of the emulsion or preparation method described in the foregoing embodiments in the preparation of food, cosmetics and pharmaceuticals.

[0011] The present invention has the following beneficial effects: This invention optimizes the antisolvent phase and employs antisolvent collision technology to construct an efficient mixing system. It precisely controls the dynamic solubility of the system to guide the orderly self-assembly of flavonoids, forming flavonoid nanoparticle emulsifiers whose particle size is precisely controlled by the solvent collision temperature. As an emulsifier, the flavonoid nanoparticles achieve the construction of an antioxidant oil-water interface, avoiding the drawbacks of requiring large amounts of synthetic surfactants in existing technologies. This effectively improves the bioavailability and oxidative stability of functional, easily oxidized oils, providing a new solution for the efficient delivery of different types of easily oxidized functional oils and slightly soluble flavonoids. Attached Figure Description

[0012] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0013] Figure 1 The emulsion prepared in Example 1; Figure 2 The emulsion obtained in Example 2; Figure 3 The emulsion prepared in Example 3; Figure 4 The emulsion obtained in Comparative Example 1; Figure 5 The emulsion obtained in Comparative Example 2; Figure 6 The particle size distribution of the flavonoid particles in Example 2; Figure 7 The particle size distribution of the flavonoid particles in Example 3; Figure 8 The particle size distribution of the flavonoid particles in Comparative Example 4 is shown. Figure 9 An optical microscope image of the flavonoid particle-based emulsion of Example 2; Figure 10 An optical microscope image of the flavonoid particle-based emulsion of Example 3; Figure 11 This is an optical microscope image of the flavonoid particle-based emulsion in Comparative Example 4. Detailed Implementation

[0014] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0015] On one hand, embodiments of the present invention provide an emulsion, the raw materials of which, by volume percentage, include: 15%~47.5% solvent phase, 15%~47.5% antisolvent phase and 5%~70% oil phase; The solvent phase is obtained by dissolving flavonoids in water at a first set temperature; the antisolvent phase is water or an ice-water mixture at a second set temperature, wherein the first set temperature is greater than the second set temperature.

[0016] In some embodiments, the volume percentage of the solvent phase is any one or any two of 15%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 42%, 44%, 46%, and 47.5%.

[0017] In some embodiments, the first set temperature is 45~100℃, specifically it can be any one or any two of the following: 45, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98 and 100℃.

[0018] In some embodiments, the concentration of flavonoids in the solvent phase is 2 to 40 mg / mL, specifically any one or any two of the following: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and 40 mg / mL.

[0019] In some embodiments, the pH of the solvent phase is 4.0 to 6.5, specifically any one or any two of 4.0, 4.2, 4.4, 4.6, 4.8, 5.0, 5.2, 5.4, 5.6, 5.8, 6.0, 6.2, 6.4 and 6.5.

[0020] In some embodiments, the volume percentage of the antisolvent phase is any one or any two of 15%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 42%, 44%, 46%, and 47.5%.

[0021] In some embodiments, the second set temperature is 0~28°C, specifically it can be any one or any two of 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 28°C.

[0022] In some embodiments, the proportion of liquid water in the ice-water mixture is 0-25% (v / w), and the equilibrium temperature is 0°C. Specifically, this proportion can be any one or a range between any two of the following: 0%, 2%, 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, and 25%.

[0023] In some embodiments, the pH of the antisolvent phase is 6.5 to 7.5, specifically any one or any two of 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4 and 7.5.

[0024] In some embodiments, the flavonoids include slightly soluble flavonoids.

[0025] In some embodiments, the flavonoids include one or more of the following: quercetin, dihydroquercetin, naringin, baicalin, rutin, wogonin, isorhamnetin, hesperidin, myricetin, dihydromyricetin, kaempferol, apigenin, and luteolin.

[0026] In some embodiments, the volume percentage of the oil phase is any one or any two of the following: 5%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 42%, 44%, 46%, 48%, 50%, 52%, 54%, 56%, 58%, 60%, 62%, 64%, 66%, 68%, and 70%.

[0027] In some embodiments, the oil phase comprises easily oxidizable oils dissolved with functional ingredients, the functional ingredients including any one or more of β-carotene, vitamin A, vitamin D, vitamin E, vitamin K, conjugated linoleic acid, α-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), coenzyme Q10, phytosterols, and phytoterpenes.

[0028] In some embodiments, the concentration of the easily oxidizable oil in the oil phase is 1~20 mg / mL, specifically any one or any two of 1, 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 mg / mL.

[0029] In some embodiments, the easily oxidized oils include one or more of fish oil, krill oil, astaxanthin oil, algae oil, and vitamin oil.

[0030] In some embodiments, the particle size of the flavonoid nanoparticles in the emulsion is 200-850 nm, specifically any one or any two of the following ranges: 200, 210, 220, 230, 236, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, 500, 520, 540, 560, 580, 600, 620, 640, 660, 680, 700, 720, 740, 760, 780, 800, 820, 840, and 850 nm.

[0031] On the other hand, embodiments of the present invention provide a method for preparing an emulsion as described in any of the foregoing embodiments, which includes preparation using the raw materials described in any of the foregoing embodiments.

[0032] In some embodiments, the preparation includes the following steps: subjecting the solvent phase, oil phase and antisolvent phase described in any of the foregoing embodiments to high-speed shearing to obtain an emulsion.

[0033] In some embodiments, the solvent phase, the oil phase, and the antisolvent phase are fed through three pipelines; In some embodiments, the preparation is carried out in a multilayer stator emulsification device, which includes a dual multilayer stator comprising a first stator, a second stator, and a third stator; the solvent phase and the antisolvent phase are premixed in the first and second stators and then enter the third stator, while the oil phase is injected into the third stator to complete the emulsification.

[0034] Furthermore, the emulsions or preparation methods described in any of the foregoing embodiments may be used in the preparation of food, cosmetics, and pharmaceuticals.

[0035] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0036] Example 1 A flavonoid-based oxidatively stabilized functional emulsion, the raw materials of which are as follows.

[0037] (1) Solvent phase: Dihydromyricetin was dissolved in water at 90℃ as the solvent phase; the concentration of dihydromyricetin was 20 mg / mL, and the pH of the solvent phase was 5.3; (2) Antisolvent phase: Water at 20℃ is used as the antisolvent phase, and the pH of the antisolvent phase is 7.0; (3) Oil phase: The oil phase containing dissolved β-carotene, the concentration of β-carotene is 5 mg / mL, and the oil phase is sunflower seed oil.

[0038] The preparation method is as follows: The solvent phase and antisolvent phase were injected separately at a 1:1 (v / v) ratio through a three-channel feeding system. After mixing in the first and second stators, an aqueous phase was obtained. Flavonoid particles with a uniform size distribution of 800 nm were dispersed in the aqueous phase, and the particles were partially separated after standing and cooling for 12 hours. The oil phase containing dissolved β-carotene was fed into the third stator along with the aqueous phase. The mixture was mixed at a ratio of 1:9 (v / v) for 30 s, and then homogenized by high-speed shearing at 6000 rpm to obtain a flavonoid particle-based emulsion.

[0039] The final emulsion developed a precipitated layer after one day, with a small amount of crystals precipitated in the bottom aqueous phase. No oil precipitation was observed. The emulsion exhibited a distinct oil-in-water microstructure, and oil droplets of varying diameters (ranging from 25 μm to 30 μm) were visible. Figure 1 .

[0040] Example 2 A flavonoid-based oxidatively stabilized functional emulsion, the raw materials of which are as follows.

[0041] (1) Solvent phase: Dihydromyricetin was dissolved in water at 90℃ as the solvent phase; the concentration of dihydromyricetin was 20 mg / mL, and the pH of the solvent phase was 5.3; (2) Antisolvent phase: Water at 4°C is used as the antisolvent phase, and the pH of the antisolvent phase is 7.0; (3) Oil phase: Same as in Example 1.

[0042] The preparation method is the same as in Example 1. The solvent phase and the antisolvent phase are mixed at a ratio of 1:1 (v / v) to obtain an aqueous phase. Flavonoid particles with a particle size of 372 nm and uniform size distribution are dispersed in the aqueous phase. The particles are partially separated after standing and cooling for 12 hours.

[0043] After the final emulsion was prepared and left for one day, emulsification occurred, but this was less severe than in Example 1. No crystals precipitated in the bottom aqueous phase, and no oil precipitation was observed. The emulsion exhibited a distinct oil-in-water microstructure, with smaller (15 μm-18 μm) and more uniform oil droplets observed. The physical and oxidative stability of the emulsion was improved. Figure 2 .

[0044] Example 3 A flavonoid-based oxidatively stabilized functional emulsion, the raw materials of which are as follows.

[0045] (1) Solvent phase: Dihydromyricetin was dissolved in water at 90℃ as the solvent phase; the concentration of dihydromyricetin was 20 mg / mL, and the pH of the solvent phase was 5.3; (2) Antisolvent phase: An ice-water mixture with an ice content of 15% (v / w) (equilibrium temperature of 0℃) was used as the antisolvent phase, and the pH of the antisolvent phase was 7.0; (3) Oil phase: Same as in Example 1.

[0046] The preparation method is the same as in Example 1.

[0047] The flavonoid particles in the aqueous phase had a diameter of 225 nm and a uniform size distribution, with no crystal precipitation. After the final emulsion was prepared and left for one day, emulsification occurred, but this was less pronounced than in Example 2. No crystals precipitated in the bottom aqueous phase, and no oil precipitation was observed. The emulsion exhibited a distinct oil-in-water microstructure, with small (13 μm-15 μm) and uniform oil droplets. The physical and oxidative stability of the emulsion was further improved. Figure 3 .

[0048] Example 4 A flavonoid-based oxidatively stabilized functional emulsion, whose raw materials and preparation method are roughly the same as in Example 1, except that the water temperature for dissolving dihydromyricetin in the solvent phase is 45°C.

[0049] Short-term (10 minutes) oil-water separation of flavonoid particle-based emulsions was achieved, with flavonoid crystals precipitating in the aqueous phase and oil droplets rapidly coalescing.

[0050] Example 5 A flavonoid-based oxidatively stabilized functional emulsion, whose raw materials and preparation method are roughly the same as in Example 1, except that the antisolvent phase is water and the temperature is 10°C.

[0051] In flavonoid particle-based emulsions, flavonoid crystal precipitation is reduced, the emulsion has no oil layer, and physical and oxidative stability is improved.

[0052] Example 6 A flavonoid-based oxidatively stabilized functional emulsion, whose raw materials and preparation method are roughly the same as those in Example 1, except that: the water temperature for dissolving dihydromyricetin in the solvent phase is 90°C; the antisolvent phase is an ice-water mixture with an ice content of 20% v / w.

[0053] Flavonoid particle-based emulsions do not precipitate flavonoid crystals, the emulsions are free of oil precipitation, and their physical and oxidative stability is improved.

[0054] Comparative Example 1 A flavonoid-based oxidatively stabilized functional emulsion, the raw materials of which are as follows.

[0055] (1) Solvent phase: Dihydromyricetin was dissolved in water at 45℃ as the solvent phase; the concentration of dihydromyricetin was 20 mg / mL, and the pH of the solvent phase was 5.3; (2) Antisolvent phase: None; (3) Oil phase: The oil phase containing dissolved β-carotene, the concentration of β-carotene is 5 mg / mL, and the oil phase is sunflower seed oil.

[0056] The preparation method is as follows: Dihydromyricetin precipitates before mixing. The solvent phase and the oil phase containing dissolved β-carotene are mixed at a ratio of 9:1 (v / v) for 30 s using a dual-channel method. After high-speed shearing and homogenization at 6000 rpm, a flavonoid-based emulsion is obtained.

[0057] The final emulsion separated into oil and water phases within 1 minute. A large number of crystals precipitated from the bottom aqueous phase. The microstructure of the emulsion consisted of large, irregular oil clumps, with the oil droplets largely coalescing and breaking down. Figure 4 .

[0058] Comparative Example 2 A flavonoid-based oxidatively stabilized functional emulsion, the raw materials of which are as follows.

[0059] (1) Solvent phase: Dihydromyricetin was dissolved in water at 90℃ as the solvent phase; the concentration of dihydromyricetin was 20 mg / mL, and the pH of the solvent phase was 5.3; (2) Antisolvent phase: None; (3) Oil phase: same as comparative example 1.

[0060] The preparation method was the same as in Comparative Example 1. No precipitate formed from the dihydromyricetin raw material before mixing. After 6 hours of natural cooling, the oil and water phases of the final emulsion separated. A large number of crystals precipitated in the bottom aqueous phase, while oil precipitated at the top. The microstructure of the emulsion consisted of large, irregular oil clumps, with most oil droplets coalescing and breaking down. (See...) Figure 5 .

[0061] Comparative Example 3 A flavonoid-based oxidatively stabilized functional emulsion, whose raw materials and preparation method are roughly the same as in Example 3, except that: there is no antisolvent phase; the water temperature for dissolving dihydromyricetin in the solvent phase is 75°C.

[0062] The flavonoid particle-based emulsion exhibited oil separation within a short period (20 min), with a large amount of oil droplets coalescing.

[0063] Comparative Example 4 A flavonoid-particulate-based oxidation-stabilized functional emulsion, the preparation method of which is as follows: At room temperature, 20 mg / mL dihydromyricetin was dissolved in DMSO solution and mixed with distilled water (antisolvent) at a ratio of 1:1 (v / v). After stirring evenly, the DMSO was removed by rotary evaporation to obtain a flavonoid suspension.

[0064] The oil phase (same as in Example 1) and the flavonoid suspension were mixed at a ratio of 1:9 (v / v) to prepare an emulsion under the same conditions as in Example 1.

[0065] Experimental Example 1 (1) Average particle size of flavonoid particles.

[0066] The average particle size of the flavonoid nanoparticles in Examples 2, 3, and 4 was measured, and the results are shown in the table below. Figure 6 , Figure 7 and Figure 8 .

[0067] The results show that the flavonoid particles in Example 2 have an average particle size of 372 nm and are uniform in size, the flavonoid particles in Example 3 have an average particle size of 225 nm and are uniform in size, and the flavonoid particles in Comparative Example 4 have an average particle size of 272.6 nm, are non-uniform in size, and contain large aggregates.

[0068] (2) Microstructure of flavonoid particulate emulsion The microstructure of the flavonoid nanoparticle-based emulsions in Examples 2, 3, and 4 was examined, and the optical microscope images are shown below. Figure 9 , Figure 10 and Figure 11 .

[0069] The results show that the droplets in Examples 2 and 3 are mainly small spherical, with small droplet size, concentrated distribution (narrow distribution), high droplet density, good dispersibility, and no obvious large particle aggregation. This indicates that the particle characteristics of Examples 2 and 3 are controllable (i.e., the emulsion is controllable). In contrast, the droplets in Comparative Example 4 are mainly near-spherical, with some irregularly shaped droplets, uneven droplet size (wide distribution), and violent aggregation of small droplets, indicating that the emulsion in Comparative Example 4 has poor emulsification performance.

[0070] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. An emulsion characterized in that, The raw materials include, in volume percentage, 15-47.5% solvent phase, 15-47.5% anti-solvent phase and 5-70% oil phase; The solvent phase is obtained by dissolving flavones in water at a first set temperature; and the anti-solvent phase is water at a second set temperature or an ice-water mixture, wherein the first set temperature is higher than the second set temperature.

2. The emulsion of claim 1, wherein, The first set temperature is 45-100℃.

3. The emulsion of claim 1, wherein, The concentration of flavones in the solvent phase is 2-40 mg / mL. The pH of the solvent phase is 4.0-6.

5.

4. The emulsion of claim 1, wherein, The second set temperature is 0-28℃. The proportion of liquid water in the ice-water mixture is 0-25% (v / w) and the equilibrium temperature is 0℃. The pH of the anti-solvent phase is 6.5-7.

5.

5. The emulsion of claim 1, wherein, The oil phase includes oxidizable oil dissolving functional ingredients, which include any one or more of β-carotene, vitamin A, vitamin D, vitamin E, vitamin K, conjugated linoleic acid, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, coenzyme Q10, phytosterol and phytoterpene; The oxidizable oil includes one or more of fish oil, krill oil, astaxanthin oil, seaweed oil and vitamin oil. The concentration of the oxidizable oil in the oil phase is 1-20 mg / mL.

6. The emulsion according to any one of claims 1 to 5, characterized in that, The flavones include slightly soluble flavones. The flavones include one or more of quercetin, dihydroquercetin, bakuchin, baicalin, luteolin, wogonin, isorhamnetin, hesperidin, myricetin, dihydromyricetin, kaempferol, apigenin and luteolin.

7. The emulsion according to any one of claims 1 to 5, wherein The particle size of the flavone nanoparticles in the emulsion is 200-850 nm.

8. The method of preparing an emulsion according to any one of claims 1 to 7, wherein The preparation method includes the following steps: high-speed shearing treatment of the solvent phase, the oil phase and the anti-solvent phase in the raw materials to obtain an emulsion.

9. The production method according to claim 8, characterized by, The solvent phase, the oil phase and the anti-solvent phase are fed through three pipes. The preparation is performed in a multi-layer stator emulsification device, which includes a pair of multi-layer stators comprising a first stator, a second stator and a third stator; the solvent phase and the anti-solvent phase are pre-mixed in the first stator and the second stator and then enter the third stator, while the oil phase is injected into the third stator to complete the emulsification.

10. Use of the emulsion of any one of claims 1-7 or the preparation method of claim 8 or 9 in the preparation of food, cosmetics and drugs. ​

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