Composite encapsulated vitamin liposome, preparation method, and use

Abstract

A composite encapsulated vitamin liposome, which is prepared from the following raw materials in parts by weight: 2-65 parts of a vitamin, 15-65 parts of a phospholipid, 0.2-3 parts of an antioxidant, 1-8 parts of a membrane stabilizer, 9-45 parts of a first-layer wall material, and 4-20 parts of a second-layer wall material. A preparation method comprises: preparing an aqueous solution of a water-soluble vitamin to obtain an aqueous phase; fully mixing and dissolving anhydrous ethanol, a phospholipid and a membrane stabilizer, and then adding a lipid-soluble vitamin and allowing same to completely dissolve to obtain an alcohol phase; separately preparing a first-layer wall material solution and a second-layer wall material solution; slowly injecting the alcohol phase into the aqueous phase, and stirring same sufficiently to form a primary liposome dispersion solution; performing vacuum concentration to obtain a concentrated solution, slowly adding same to the first-layer wall material solution, and stirring same sufficiently to form a dispersion solution; and performing high speed shearing and high pressure homogenization and mixing same with the second-layer wall material solution, and performing drying to obtain the final product. The liposome can be used in the production of tablet preparations, hard-shell capsules and solid beverages, and can achieve high stability and controlled release of vitamins.

Description

A composite encapsulated vitamin liposome, its preparation method and application Cross-references

[0001] This application claims priority to Chinese application No. 202411938946.2, filed on December 26, 2024, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This specification relates to the field of food nutrition and health, and in particular to a complex encapsulated vitamin liposome and its preparation method. Through unique formulation design and optimized preparation process, this complex achieves efficient encapsulation and stable release of vitamins, significantly improving the product's bioavailability and market application value. Background Technology

[0003] Vitamins, as essential nutrients for the human body, play a vital role in the food industry. However, traditional vitamin preparations suffer from poor stability and low bioavailability, especially in the mixed application of water-soluble and fat-soluble vitamins. Liposomes, as a nanomedicine delivery system, can effectively improve drug stability and bioavailability due to their unique bilayer membrane structure and have been widely used in the pharmaceutical field. In recent years, liposome technology has also been gradually introduced into the food industry to improve the delivery efficiency of functional ingredients.

[0004] Liposome technology, as an advanced drug delivery system, has rapidly become a research hotspot in multiple fields since its first report in the 1960s. Liposomes are vesicle structures formed by encapsulating hydrophilic or hydrophobic components within a phospholipid bilayer, with diameters typically ranging from tens of nanometers to several micrometers. This unique structure endows liposomes with many superior properties, such as good biocompatibility and tunable particle size.

[0005] Liposome technology has been widely used to improve the stability of drug components, increase drug targeting, prolong the duration of drug action, and reduce drug side effects. By encapsulating drug molecules inside liposomes, drugs can be effectively protected from external environmental damage, such as enzymatic hydrolysis and oxidation, thereby improving drug stability and bioavailability. Furthermore, the phospholipid molecules on the surface of liposomes are structurally similar to cell membranes, allowing liposomes to penetrate cell membranes more easily, improving transdermal absorption and cellular uptake efficiency.

[0006] With the fast pace of modern life and increasing work pressure, sub-health conditions are prevalent, and consumers' demand for health management is growing. At the same time, the government is strengthening its supervision of the dietary supplement industry, and policies and regulations are gradually being improved, providing strong support for the healthy development of the industry. Liposome preparations are increasingly being used in food and health products to address issues such as poor nutrient stability, poor absorption, low bioavailability, and the tendency to cause gastrointestinal discomfort.

[0007] Existing liposome vitamin complexes are mostly prepared using a single method, which has certain limitations in terms of particle size control, stability, and production efficiency. Summary of the Invention

[0008] This specification provides one or more embodiments of a composite encapsulated vitamin liposome, prepared from the following raw materials in parts by weight: 2-65 parts vitamin, 15-65 parts phospholipid, 0.2-3 parts antioxidant, 1-8 parts membrane stabilizer, 9-45 parts first-layer wall material, and 4-20 parts second-layer wall material.

[0009] This specification provides one or more embodiments of a method for preparing the above-mentioned composite encapsulated vitamin liposomes, which includes the following steps:

[0010] S1. Aqueous phase preparation: Prepare a water-soluble vitamin aqueous solution;

[0011] S2. Alcohol phase preparation: After thoroughly mixing and dissolving anhydrous ethanol, the phospholipid, and the film stabilizer, add the fat-soluble vitamin until completely dissolved;

[0012] S3. Preparation of wall material solution: Prepare one layer of wall material solution and two layers of wall material solution respectively;

[0013] S4. Slowly inject the alcohol phase into the aqueous phase, stir thoroughly to form a preliminary liposome dispersion solution, concentrate under reduced pressure to obtain a concentrated solution, and slowly add it to the single-walled solution obtained in step S3, stir thoroughly to form a composite encapsulated liposome dispersion solution; and

[0014] S5. The composite encapsulated liposome dispersion solution obtained in step S4 is subjected to high-speed shearing and high-pressure homogenization. The homogenized layer of encapsulated liposome dispersion solution is mixed with the second layer of wall material solution and then dried to obtain the composite encapsulated vitamin liposome.

[0015] This specification provides one or more embodiments for the application of the above-described composite encapsulated vitamin liposomes, including the preparation of tablets, hard-shell capsules, and solid beverages. Detailed Implementation

[0016] To further illustrate the technical means and their effects adopted in this specification, the following description is based on preferred embodiments of this specification to further explain the technical solutions of this specification. However, this specification is not limited to the scope of the embodiments.

[0017] This specification provides a composite encapsulated vitamin liposome, its preparation method, and its applications. Through an optimized formulation and process combination, and an innovative integration of ethanol injection and three-fluid coaxial spray drying, the aim is to provide a liposomal vitamin complex with good flowability, small particle size, high encapsulation efficiency, excellent reconstitution properties, and significantly improved bioavailability. This process improves the stability of the liposomes while simplifying the production process and reducing production costs, making it more suitable for the industrial production of food and pharmaceutical formulations. The composite encapsulated liposomes prepared by this invention have good flowability and small particle size, and can be applied to tableting, hard-shell capsules, and solid beverages.

[0018] This specification provides a composite encapsulated vitamin liposome, prepared from the following raw materials in parts by weight: 2-65 parts vitamins, 15-65 parts phospholipids, 0.2-3 parts antioxidants, 1-8 parts membrane stabilizers, 9-45 parts of a first-layer wall material, and 4-20 parts of a second-layer wall material. In some embodiments, the composite encapsulated vitamin liposome may further include the following raw materials prepared in parts by weight: 2-50 parts vitamins, 25-65 parts phospholipids, 0.2-2.5 parts antioxidants, 1-5.5 parts membrane stabilizers, 10-45 parts of a first-layer wall material, and 5-20 parts of a second-layer wall material. In each embodiment, the weight of each component is expressed in parts; however, these parts by weight can also be directly converted into weight ratios or calculated into weight percentages in the total.

[0019] In some embodiments, the vitamins include at least one of water-soluble vitamins or fat-soluble vitamins.

[0020] In some embodiments, the complex encapsulated vitamin liposome may include 12-65 parts of water-soluble vitamins and 2-20 parts of fat-soluble vitamins. In some embodiments, the complex encapsulated vitamin liposome may also include 30-65 parts of water-soluble vitamins, or 5-20 parts of fat-soluble vitamins, or simultaneously loaded with both water-soluble and fat-soluble vitamins.

[0021] In some embodiments, the requirements for vitamin compound use can also be met, with the content ratio of water-soluble vitamins to fat-soluble vitamins being (3-15):1. This ratio range ensures good encapsulation efficiency and stability while adapting to the needs of different application scenarios. In some embodiments, the content ratio of water-soluble vitamins to fat-soluble vitamins can also be (4-10):1.

[0022] In some embodiments, the water-soluble vitamin may be selected from one or more of vitamin C, vitamin B1, vitamin B2, vitamin B6, and vitamin B12.

[0023] In some embodiments, the fat-soluble vitamin may be selected from one or more of vitamin A, vitamin D, vitamin E, vitamin K1, and vitamin K2.

[0024] In some embodiments, the phospholipid is selected from one or more of soybean lecithin, sunflower lecithin, and rapeseed lecithin.

[0025] In some embodiments, the acetone-insoluble content in the phospholipid is required to be greater than 60%, and the acetone-insoluble content can be greater than 90%, or even greater than 95%.

[0026] In some embodiments, the phosphatidylcholine content in the phosphatidylcholine is required to be greater than 50%, and the phosphatidylcholine content can be greater than 70%, or even greater than 90%. High-purity phosphatidylcholine such as soybean lecithin PC90 and above is selected in the examples.

[0027] In some embodiments, the film stabilizer includes one or more of phytosterols, mono- and diglycerides of fatty acids, fatty acids, and vegetable oils.

[0028] In some embodiments, the weight ratio of the film stabilizer to the phosphatidylcholine component in the phospholipid is 1:3-1:15. In some embodiments, the weight ratio of the film stabilizer to the phosphatidylcholine component in the phospholipid can be 1:3-1:12, 1:4-1:10, or 1:4-1:8.

[0029] In some embodiments, the phytosterols are selected from one or more of sitosterol, stigmasterol, rapeseed sterol, ergosterol, and microalgesterol.

[0030] In some embodiments, to ensure the stability of the liposomes, the melting points of the aforementioned mono- and diglyceride fatty acid esters, fatty acids, and vegetable oils are required to be between 40 and 90°C. In some embodiments, the melting points of the aforementioned mono- and diglyceride fatty acid esters, fatty acids, and vegetable oils may also be between 40 and 80°C, or between 45 and 65°C.

[0031] In some embodiments, the antioxidant is selected from one or more of ascorbic acid, ascorbyl palmitate, mixed tocopherols, citrus flavonoids, proanthocyanidins, tea polyphenols, and carotenoids.

[0032] In some embodiments, the first layer of wall material includes one or more of modified starch, gum arabic, maltodextrin, resistant dextrin, maltodextrin, and isomaltodextrin; the second layer of wall material includes one or more of hydroxypropyl methylcellulose, hydroxypropyl ethylcellulose, methylcellulose, ethylcellulose, carboxymethylcellulose, and sodium carboxymethylcellulose.

[0033] In some embodiments, the weight ratio of the first layer of wall material to the second layer of wall material is (1-5):1. In some embodiments, the weight ratio of the first layer of wall material to the second layer of wall material can be (2-3):1.

[0034] This specification provides an embodiment of a method for preparing a complex encapsulated vitamin liposome, which includes the following steps:

[0035] S1. Aqueous phase preparation: Prepare a water-soluble vitamin aqueous solution;

[0036] S2. Alcohol phase preparation: After thoroughly mixing and dissolving anhydrous ethanol, phospholipids, and film stabilizers, add fat-soluble vitamins until completely dissolved;

[0037] S3. Preparation of wall material solution: Prepare one layer of wall material solution and two layers of wall material solution respectively;

[0038] S4. Slowly inject the alcohol phase into the aqueous phase, stir thoroughly to form a preliminary liposome dispersion solution, concentrate under reduced pressure to obtain a concentrated solution, and slowly add it to the wall material solution obtained in step S3, stir thoroughly to form a composite embedded liposome dispersion solution; and

[0039] S5. The composite encapsulated liposome dispersion solution obtained in step S4 is subjected to high-speed shearing and high-pressure homogenization. The homogenized layer of encapsulated liposome dispersion solution is mixed with the second layer of wall material solution and then dried to obtain composite encapsulated vitamin liposomes.

[0040] In some embodiments, the dissolving temperature of water-soluble vitamins in step S1 is 30-70°C. In some embodiments, the dissolving temperature of water-soluble vitamins can be 40-60°C or 45-55°C.

[0041] In some embodiments, in order to reduce the degradation of water-soluble vitamins during sample preparation, the dissolution process of water-soluble vitamins in step S1 should be carried out in a light-proof, inert gas environment.

[0042] In some embodiments, in step S2, the dissolution temperature of the phospholipid and the film stabilizer is 40–70°C. In some embodiments, the dissolution temperature of the phospholipid and the film stabilizer can be 50–65°C or 55–60°C.

[0043] In some embodiments, to reduce the degradation of fat-soluble vitamins during sample preparation, in step S2, before adding the fat-soluble vitamins, the temperature of the alcohol phase is adjusted to 35-60°C and maintained until the fat-soluble vitamins are completely dissolved. More preferably, it is 40-50°C. More preferably, the dissolution temperature of fat-soluble vitamins in the alcohol phase is 40-50°C, and the dissolution process requires a light-protected, inert gas environment.

[0044] In some embodiments, the weight ratio of deionized water in step S1 to anhydrous ethanol in step S2 should be within a certain range. The weight ratio of water to anhydrous ethanol is (1-8):1, and the weight ratio of water to anhydrous ethanol can also be (1-5):1 or (2-4):1.

[0045] In some embodiments, in step S3, the solid content of the first layer of wall material solution is 20-60 wt%. In some embodiments, the solid content of the first layer of wall material solution can be 30-45 wt%. In some embodiments, the solid content of the first layer of wall material solution can also be 35-45 wt%. In some embodiments, the solid content of the second layer of wall material solution is 1-10 wt%. In some embodiments, the solid content of the second layer of wall material solution can be 3-8 wt%. In some embodiments, the solid content of the second layer of wall material solution can also be 5-8 wt%.

[0046] In some embodiments, in step S4, the temperature of the vacuum concentration process is 30-70°C; the temperature can also be 40-60°C or 45-55°C.

[0047] In some embodiments, in step S4, the vacuum degree of the reduced pressure concentration process is -0.1 to 0.07 MPa; the vacuum degree can also be -0.1 to 0.08 MPa or -0.09 to 0.085 MPa.

[0048] In some embodiments, the stirring temperature after adding the wall material aqueous solution in step S4 is 40-60°C, and the temperature can also be 40-50°C.

[0049] In some embodiments, the homogenization pressure in step S5 is 20-40 MPa; the homogenization pressure can also be 30-40 MPa; preferably, the homogenization is performed twice.

[0050] In some embodiments, the drying method in step S5 can be selected from one of spray drying, low-temperature spray drying, freeze drying, and freeze-spray drying. In some embodiments, to better meet the needs of industrialization, the drying method in step S5 is selected as spray drying or low-temperature spray drying. In some embodiments, for vitamin components with poor thermal stability, low-temperature spray drying is selected as the drying method, and for heat-stable vitamin components, spray drying is selected as the drying method.

[0051] In some embodiments, in step S5, the feed nozzle matched with the spray drying tower or low-temperature spray drying tower used for drying is a three-fluid coaxial two-phase nozzle.

[0052] In some embodiments, in step S5, the mixing of the first layer of embedded liposome dispersion solution and the second layer of wall material solution is carried out using a two-phase nozzle mixing method. The first layer of embedded liposome dispersion solution and the second layer of wall material solution are respectively introduced into the inner and outer phase feed channels of the three-fluid coaxial spray drying tower, and the inner and outer phase liquids are sprayed out simultaneously to form a liquid-liquid bilayer droplet morphology, further achieving bilayer embedding and solidification during the drying process.

[0053] Finally, the embodiments in this specification also provide applications of the above-mentioned composite encapsulated vitamin liposomes, including the production of tablets, hard-shell capsules, and solid beverages, among which solid beverages include fruit and vegetable solid beverages, protein solid beverages, tea solid beverages, and plant solid beverages.

[0054] In some embodiments of this specification, liposomes are used as carriers to encapsulate multiple water-soluble and fat-soluble vitamins. The resulting composite encapsulated vitamin liposomes exhibit good flowability, uniform particle size, no unpleasant odor, and a rehydrated particle size in the range of 200nm-800nm. The composite encapsulated vitamin liposomes prepared in these embodiments, after being encapsulated with two layers of wall material, possess excellent physical and chemical stability. After accelerated treatment at 60°C for 20 days, the resulting liposomes did not exhibit problems such as clumping, browning, or deterioration of odor, and the content degradation rate was less than 5%. The composite encapsulated vitamin liposomes prepared in the examples of this specification use high-purity phospholipids from natural plant sources as raw materials, and the formulation does not contain cholesterol, thus better meeting consumer needs. The preparation method of the composite encapsulated vitamin liposomes described in the examples of this specification uses clean solvent ethanol as a processing aid, and removes and recovers it during the process. The solvent residue in the product is less than 50 ppm, which meets the requirements of food processing industry regulations and does not cause environmental pollution. The preparation method of the composite encapsulated vitamin liposomes described in the examples of this specification simplifies the complex steps of traditional liposome preparation. This invention reduces production difficulty and cost while improving production efficiency; it has excellent industrial adaptability and can meet the needs of large-scale product production; the composite encapsulated vitamin liposomes prepared in the examples of this specification have wide applications and can be widely used in various tablet formulations, hard-shell capsules, solid beverages, and other dietary supplements and functional health foods; the composite encapsulated vitamin liposomes prepared in the examples of this specification can significantly improve the bioavailability of vitamins, ensuring that the human body absorbs and utilizes vitamin components more efficiently; the composite encapsulated vitamin liposomes prepared in the examples of this specification can be rapidly dispersed and dissolved in water or other media to form a uniform and stable solution, suitable for the application needs of various dosage forms; the composite encapsulated vitamin liposomes prepared in the examples of this specification are encapsulated with two layers of wall material using three-fluid coaxial two-phase spray drying technology, which simultaneously encapsulates the product with two layers of wall material during spray drying, reducing production time and greatly improving production efficiency; the composite encapsulated vitamin liposomes prepared in the examples of this specification introduce two functional wall materials, enhancing the protective effect on vitamin liposomes, enhancing their sustained-release effect, and significantly improving the bioavailability of vitamins.

[0055] For those skilled in the art, various modifications and changes can be made to the process under the guidance of this specification. However, these modifications and changes are still within the scope of this specification. Examples

[0056] The present invention will be further described below with reference to embodiments, but it should be understood that the scope of protection of the present invention is not limited to the embodiments. Embodiment 1

[0057] Aqueous phase: Weigh 240 parts of deionized water, heat to 50°C, add 65 parts of vitamin C and 0.5 parts of citrus flavonoids, and stir until completely dissolved.

[0058] Alcohol phase: Weigh 30 parts of anhydrous ethanol, add 15 parts of soybean lecithin PC90 (PC90: phosphatidylcholine content ≥90%, the same below) and 2 parts of mono- and diglyceride fatty acid esters, heat to 60℃, and stir until completely dissolved.

[0059] One layer of wall material solution: Add 9.5 parts of modified starch to 18 parts of deionized water, heat and stir until completely dissolved.

[0060] Second-layer wall material solution: Add 8 parts of hydroxypropyl methylcellulose to 133 parts of deionized water, heat and stir until completely dissolved.

[0061] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.09 MPa and 60°C.

[0062] Vitamin C liposome concentrate was added to a first-layer wall material solution and stirred at 45°C for 1 hour. The solution was then subjected to high-speed shearing at 5500 rpm for 2 minutes and homogenized twice under high pressure at 35 MPa. Subsequently, it and the second-layer wall material aqueous solution were subjected to coaxial two-phase spray drying, with the inlet air temperature controlled at 130°C and the outlet air temperature at 80°C, to obtain vitamin C liposome microcapsule powder. Example 2

[0063] Aqueous phase: Weigh 200 parts of deionized water, heat to 50°C, add 45 parts of vitamin B6 and 1 part of grape seed extract, and stir until completely dissolved.

[0064] Alcohol phase: Weigh 90 parts of anhydrous ethanol, add 35 parts of sunflower lecithin PC70 and 3 parts of palm oil, heat to 60°C, and stir until completely dissolved.

[0065] One layer of wall material solution: Add 12 parts of gum arabic to 48 parts of deionized water, heat and stir until completely dissolved.

[0066] Second-layer wall material solution: Add 4 parts sodium carboxymethyl cellulose to 60 parts deionized water, heat and stir until completely dissolved.

[0067] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.1 MPa and 50°C.

[0068] Vitamin B6 liposome concentrate was added to a first-layer wall material solution and stirred at 40°C for 1 hour. The solution was then subjected to high-speed shearing at 5000 rpm for 3 minutes and homogenized twice under high pressure at 40 MPa. Subsequently, it and the second-layer wall material solution were subjected to coaxial two-phase spray drying, with the inlet air temperature controlled at 140°C and the outlet air temperature at 82°C, to obtain vitamin B6 liposome microcapsule powder. Example 3

[0069] Aqueous phase: Weigh 200 parts of deionized water, heat to 50℃, add 2.5 parts of tea polyphenols, and stir until completely dissolved.

[0070] Alcohol phase: Weigh 50 parts of anhydrous ethanol, add 2 parts of vitamin D3 crystals, 25 parts of soybean lecithin PC70 and 5.5 parts of stigmasterol, heat to 60℃ and stir until completely dissolved.

[0071] One layer of wall material solution: Add 8 parts of modified starch and 37 parts of maltodextrin to 90 parts of deionized water, heat and stir until completely dissolved.

[0072] Second-layer wall material solution: Add 20 parts of sodium carboxymethyl cellulose to 350 parts of deionized water, heat and stir until completely dissolved.

[0073] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.09 MPa and 50 °C.

[0074] Vitamin D3 liposome concentrate was added to a first-layer wall material solution and stirred at 40°C for 1 hour. The solution was then subjected to high-speed shearing at 5000 rpm for 3 minutes and homogenized twice under high pressure at 40 MPa. Subsequently, it and the second-layer wall material solution were subjected to coaxial two-phase spray drying, with the inlet air temperature controlled at 140°C and the outlet air temperature at 82°C, to obtain vitamin D3 liposome microcapsule powder. Example 4

[0075] Aqueous phase: Weigh 240 parts of deionized water, heat to 50℃, and set aside.

[0076] Alcohol phase: Weigh 120 parts anhydrous ethanol, add 65 parts rapeseed lecithin PC50 and 5 parts sitosterol, heat to 60℃, and stir until completely dissolved. Add 8 parts vitamin E and 0.2 parts ascorbate palmitate, and stir until completely dissolved.

[0077] One layer of wall material solution: Add 11.8 parts of maltodextrin to 20 parts of deionized water, heat and stir until completely dissolved.

[0078] Second-layer wall material solution: Add 10 parts methylcellulose to 180 parts deionized water and stir until completely dissolved.

[0079] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.085 MPa and 55°C.

[0080] Vitamin E liposome concentrate was added to a first-layer wall material solution and stirred at 40°C for 1 hour. The solution was then subjected to high-speed shearing at 5000 rpm for 3 minutes and homogenized twice under high pressure at 40 MPa. Subsequently, it and the second-layer wall material solution were subjected to coaxial two-phase spray drying, with the inlet air temperature controlled at 140°C and the outlet air temperature at 82°C, to obtain vitamin E liposome microcapsule powder. Example 5

[0081] Aqueous phase: Weigh 180 parts of deionized water, heat to 50℃, add 20 parts of vitamin B6, 10 parts of vitamin B12 and 2 parts of ascorbic acid, and stir until completely dissolved.

[0082] Alcohol phase: Weigh 90 parts of anhydrous ethanol, add 40 parts of sunflower lecithin PC80 and 3 parts of stigmasterol, heat to 60℃ and stir until completely dissolved.

[0083] One layer of wall material solution: Add 20 parts of resistant dextrin to 30 parts of deionized water, heat and stir until completely dissolved.

[0084] Second-layer wall material solution: Add 3 parts hydroxypropyl methylcellulose and 2 parts sodium carboxymethyl cellulose to 100 parts deionized water, heat and stir until completely dissolved.

[0085] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.09 MPa and 48°C.

[0086] A concentrated solution of compound vitamin B liposomes was added to a first-layer wall material solution and stirred at 40°C for 1 hour. The solution was then subjected to high-speed shearing at 5000 rpm for 3 minutes and homogenized twice under high pressure at 40 MPa. Subsequently, the solution and the second-layer wall material solution were subjected to coaxial two-phase spray drying, with the inlet air temperature controlled at 140°C and the outlet air temperature at 82°C, to obtain compound vitamin B liposome microcapsule powder. Example 6

[0087] Aqueous phase: Weigh 260 parts of deionized water, heat to 50℃, and set aside.

[0088] Alcohol phase: Weigh 150 parts anhydrous ethanol, add 50 parts soybean lecithin PC95 and 5.5 parts mono- and diglyceride fatty acid esters, heat to 60℃, and stir until completely dissolved. Add 15 parts vitamin A, 5 parts vitamin D crystals and 0.5 parts mixed tocopherols, and stir until completely dissolved.

[0089] One layer of wall material solution: Add 10 parts of resistant dextrin and 10 parts of isomaltooligosaccharide to 37 parts of deionized water, heat and stir until completely dissolved.

[0090] Two-layer wall material solution: Add 2 parts methylcellulose and 2 parts hydroxypropyl ethylcellulose to 70 parts deionized water, heat and stir until completely dissolved.

[0091] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.09 MPa and 51 °C.

[0092] A concentrated solution of compound vitamin A and D liposomes was added to a first-layer wall material solution and stirred at 40°C for 1 hour. The solution was then subjected to high-speed shearing at 5000 rpm for 3 minutes and homogenized twice under high pressure at 40 MPa. Subsequently, the solution and the second-layer wall material solution were subjected to coaxial two-phase spray drying, with the inlet air temperature controlled at 140°C and the outlet air temperature at 82°C, to obtain compound vitamin A and D liposome microcapsule powder. Example 7

[0093] Aqueous phase: Weigh 150 parts of deionized water, heat to 50℃, add 50 parts of vitamin C, and stir until completely dissolved.

[0094] Alcohol phase: Weigh 80 parts anhydrous ethanol, add 30 parts rapeseed lecithin PC70 and 1.8 parts stearic acid, heat to 60℃, and stir until completely dissolved. Add 5 parts vitamin E and 0.2 parts ascorbate palmitate, and stir until completely dissolved.

[0095] One layer of wall material solution: Add 5 parts gum arabic and 4 parts maltodextrin to 11 parts deionized water, heat and stir until completely dissolved.

[0096] Two-layer wall material solution: Add 2 parts sodium carboxymethyl cellulose and 2 parts methyl cellulose to 70 parts deionized water, heat and stir until completely dissolved.

[0097] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.08 MPa and 52 °C.

[0098] A concentrated solution of compound vitamin liposomes was added to a first-layer wall material solution and stirred at 50°C for 1 hour. The solution was then subjected to high-speed shearing at 5000 rpm for 3 minutes and homogenized twice under high pressure at 40 MPa. Subsequently, the solution and the second-layer wall material solution were subjected to coaxial two-phase spray drying, with the inlet air temperature controlled at 140°C and the outlet air temperature at 82°C, to obtain compound vitamin liposome microcapsule powder. Example 8

[0099] Aqueous phase: Weigh 210 parts of deionized water, heat to 50℃, add 12 parts of vitamin C, and stir until completely dissolved.

[0100] Alcohol phase: Weigh 110 parts anhydrous ethanol, add 45 parts sunflower lecithin PC70 and 5 parts rapeseed sterol, heat to 60℃, and stir until completely dissolved. Add 3 parts vitamin K1 and 3 parts carotenoids, and stir until completely dissolved.

[0101] One layer of wall material solution: Add 14 parts of isomaltooligosaccharide and 10 parts of gum arabic to 16 parts of deionized water, heat and stir until completely dissolved.

[0102] Second-layer wall material solution: Add 8 parts of sodium carboxymethyl cellulose to 160 parts of deionized water, heat and stir until completely dissolved.

[0103] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.085 MPa and 54 °C.

[0104] A concentrated solution of compound vitamin liposomes was added to a first-layer wall material solution and stirred at 55°C for 1 hour. The solution was then subjected to high-speed shearing at 5000 rpm for 3 minutes and homogenized twice under high pressure at 40 MPa. Subsequently, the solution and the second-layer wall material solution were subjected to coaxial two-phase spray drying, with the inlet air temperature controlled at 140°C and the outlet air temperature at 82°C, to obtain vitamin C and K liposome microcapsule powder. Example 9

[0105] Aqueous phase: Weigh 200 parts of deionized water, heat to 50℃, add 35 parts of vitamin B6 and 2 parts of ascorbic acid, and stir until completely dissolved.

[0106] Alcohol phase: Weigh 80 parts anhydrous ethanol, add 30 parts soybean lecithin PC80 and 8 parts stigmasterol, heat to 60℃, and stir until completely dissolved. Add 5 parts vitamin A and stir until completely dissolved.

[0107] One layer of wall material solution: Add 5 parts gum arabic and 5 parts maltodextrin to 15 parts deionized water, heat and stir until completely dissolved.

[0108] Second-layer wall material solution: Add 10 parts of ethyl cellulose to 125 parts of deionized water according to the weight ratio of the material to the solution, and heat and stir until completely dissolved.

[0109] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.07 MPa and 60°C.

[0110] A concentrated solution of compound vitamin liposomes was added to a first-layer wall material solution and stirred at 60°C for 1 hour. The solution was then subjected to high-speed shearing at 5000 rpm for 3 minutes and homogenized twice under high pressure at 35 MPa. Subsequently, the solution and the second-layer wall material solution were subjected to coaxial two-phase spray drying, with the inlet air temperature controlled at 140°C and the outlet air temperature at 82°C, to obtain vitamin B6 and A liposome microcapsule powder. Example 10

[0111] Aqueous phase: Weigh 200 parts of deionized water, heat to 50℃, add 30 parts of vitamin B6, and stir until completely dissolved.

[0112] Alcohol phase: Weigh 50 parts anhydrous ethanol, add 30 parts rapeseed lecithin PC50 and 1 part mono- and diglyceride fatty acid esters, heat to 60℃, and stir until completely dissolved. Add 10 parts vitamin E and 1 part carotenoid, and stir until completely dissolved.

[0113] One layer of wall material solution: Add 20 parts of maltodextrin to 37 parts of deionized water, heat and stir until completely dissolved.

[0114] Second-layer wall material solution: Add 8 parts of sodium carboxymethyl cellulose to 145 parts of deionized water, heat and stir until completely dissolved.

[0115] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.09 MPa and 45°C.

[0116] A concentrated solution of compound vitamin liposomes was added to a first-layer wall material solution and stirred at 40°C for 1 hour. The solution was then subjected to high-speed shearing at 5000 rpm for 3 minutes and homogenized twice under high pressure at 20 MPa. Subsequently, the solution and the second-layer wall material solution were subjected to coaxial two-phase spray drying, with the inlet air temperature controlled at 140°C and the outlet air temperature at 82°C, to obtain vitamin B6 and E liposome microcapsule powder. Example 11

[0117] This embodiment provides a vitamin B6 and E liposome microcapsule powder, which differs from Example 10 in that the high-pressure homogenization parameter is adjusted to 30 MPa for two high-pressure homogenizations; other raw materials, dosages, and preparation methods are the same as in Example 10. Example 12

[0118] This embodiment provides a vitamin B6 and E liposome microcapsule powder, which differs from Example 10 in that the high-pressure homogenization parameter is adjusted to 35 MPa and homogenized twice; other raw materials, dosages, and preparation methods are the same as in Example 10. Example 13

[0119] This embodiment provides a vitamin B6 and E liposome microcapsule powder, which differs from Example 10 in that the high-pressure homogenization parameter is adjusted to 40 MPa and homogenized twice; other raw materials, dosages and preparation methods are the same as in Example 10.

[0120] In the above embodiments 1-13, the following parameters were selected, as shown in Table 1: Table 1 Comparative Example 1 (with added low-grade phospholipids)

[0121] Based on Example 5, to compare the impact of phospholipid specifications on product quality, a low-specification phospholipid was used in this comparative example.

[0122] Aqueous phase: Weigh 180 parts of deionized water, heat to 50℃, add 20 parts of vitamin B6, 10 parts of vitamin B12 and 2 parts of ascorbic acid, and stir until completely dissolved.

[0123] Alcohol phase: Weigh 90 parts of anhydrous ethanol, add 40 parts of powdered sunflower phospholipid (phosphatidylcholine content ≈20%, and also contains other phospholipid components such as phosphatidylinositol and phosphatidylethanolamine) and 3 parts of stigmasterol, heat to 60℃ and stir. Since there is a large amount of ethanol-insoluble matter in the powdered phospholipid, add chloroform and keep stirring until completely dissolved.

[0124] One layer of wall material solution: Add 20 parts of resistant dextrin to 30 parts of deionized water, heat and stir until completely dissolved.

[0125] Second-layer wall material solution: Add 3 parts hydroxypropyl methylcellulose and 2 parts sodium carboxymethyl cellulose to 100 parts deionized water according to the weight ratio of the material to the solution, and heat and stir until completely dissolved.

[0126] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.09 MPa and 48°C.

[0127] A concentrated solution of compound vitamin B liposomes was added to a first-layer wall material solution and stirred at 40°C for 1 hour. The solution was then subjected to high-speed shearing at 5000 rpm for 3 minutes and homogenized twice under high pressure at 40 MPa. Subsequently, the solution and the second-layer wall material solution were coaxially spray-dried, with the inlet air temperature controlled at 140°C and the outlet air temperature at 82°C, to obtain compound vitamin B liposome microcapsule powder. Comparative Examples 2-5 (Wall Material Investigation)

[0128] Based on Example 2, the effects of single-layer wall material, double-layer wall material, and their dosage ratios on product properties are compared, as shown in Table 2. Table 2 Comparative Examples 6-8 (Stabilizer and Dosage Investigation) Table 3

[0129] Based on Examples 3 and 4, the effects of film stabilizers on product quality were compared. Comparative Examples 9-10 (Antioxidant Investigation)

[0130] Based on Example 6, the effects of antioxidants on product stability were compared, as shown in Table 4. Table 4 Comparative Example 11 (Investigation of Alcohol-Water Ratio)

[0131] Based on Example 8, to compare the effect of alcohol-water ratio on product stability, in this comparative example, the ratio of deionized water in the aqueous phase to anhydrous ethanol in the alcohol phase was reduced.

[0132] Aqueous phase: Weigh 100 parts of deionized water, heat to 50°C, add 12 parts of vitamin C, and stir until completely dissolved.

[0133] Alcohol phase: Weigh 110 parts anhydrous ethanol, add 45 parts sunflower lecithin PC70 and 5 parts rapeseed sterol, heat to 60℃, and stir until completely dissolved. Add 3 parts vitamin K1 and 3 parts carotenoids, and stir until completely dissolved.

[0134] One layer of wall material solution: Add 14 parts of isomaltooligosaccharide and 10 parts of gum arabic to 16 parts of deionized water, heat and stir until completely dissolved.

[0135] Second-layer wall material solution: Add 8 parts of sodium carboxymethyl cellulose to 160 parts of deionized water, heat and stir until completely dissolved.

[0136] The alcohol phase was slowly injected into the aqueous phase and thoroughly mixed. Then, it was transferred to a rotary evaporator flask for concentration under reduced pressure at -0.085 MPa and 54 °C.

[0137] A concentrated solution of compound vitamin liposomes was added to a first-layer wall material solution and stirred at 55°C for 1 hour. The solution was then subjected to high-speed shearing at 5000 rpm for 3 minutes and homogenized twice under high pressure at 40 MPa. Subsequently, the solution and the second-layer wall material solution were coaxially spray-dried, with the inlet air temperature controlled at 140°C and the outlet air temperature at 82°C, to obtain vitamin C and K liposome microcapsule powder. Application Example 1 (Preparation of Tablet Formulations)

[0138] Take 60 parts of liposome sample from the above examples or comparative examples, 23.5 parts of sorbitol, 15 parts of microcrystalline cellulose, and 1.5 parts of magnesium stearate, mix them evenly, and then perform direct compression tableting. Test the tablet indicators. Application Example 2 (Preparation of hard-shell capsules)

[0139] Liposome samples from the above examples or comparative examples were directly filled into capsule shells to prepare hard-shell capsules, and tablet performance indicators were tested. Application Example 3 (Preparation of Solid Beverages)

[0140] Take 35 parts of liposome sample from the above examples or comparative examples, 30 parts of erythritol, 25 parts of maltodextrin, 9.4 parts of steviol glycosides, 0.5 parts of citric acid, and 0.1 parts of edible flavoring, mix them evenly, and then granulate them into packets with a net content of 3g / packet to prepare a solid beverage. Effect Comparison Group 1, Index Evaluation

[0141] The liposome samples prepared in Examples 1-13 and Comparative Examples 1-11 were evaluated according to the following indicators, as shown in Table 5. The evaluation indicators included product state, color, odor, encapsulation efficiency, particle size, angle of repose, solvent residue, and rehydrated particle size.

[0142] Status: Visual.

[0143] Color: Visually apparent.

[0144] Smell: to smell.

[0145] Particle size: Weigh approximately 10g of sample, place it in a 40-mesh standard sieve, shake for at least 3 minutes, and calculate the 40-mesh sieve passing rate.

[0146] Encapsulation efficiency: The free vitamin content was determined using ultrafiltration or organic solvent extraction. Encapsulation efficiency = (total vitamin content - free vitamin content) / total vitamin content * 100%.

[0147] Angle of repose: Measured using an angle of repose measuring instrument.

[0148] Solvent residue: determined using a headspace sampler in conjunction with gas chromatography.

[0149] Rehydration particle size: After dissolving liposomes at a 1% concentration, the rehydrated particle size was measured using a nanoparticle size analyzer, and the average particle size was taken. Table 5. Evaluation results of liposome indicators

[0150] Based on the evaluation results of liposome indicators, the test results of indicators such as product state, color, taste, particle size, encapsulation rate, and angle of repose of different examples and comparative examples can be compared.

[0151] State: The liposomes in Examples 1-13 were all free-flowing powders, indicating that the powders had very good flowability. However, the product in Comparative Example 4 was sticky and clumped together. This was because no wall material was added to the formulation. During the spray drying process, the drying temperature was much higher than the phase transition temperature of the phospholipids, which caused the product to stick and clump together. The yield was also greatly reduced, making it unsuitable for industrial production.

[0152] Color: The color of the liposome samples is affected by the type of vitamin and the formulation. The liposomes in Examples 1-13 are off-white to light yellow. Comparative Example 1 used low-purity phospholipids, resulting in a yellow color. Comparative Examples 2 and 3 added a single-layer wall material, resulting in a slight yellow color. Comparative Example 4 did not add a wall material, resulting in a significant yellow color. In fact, the addition of high-purity lecithin and wall material makes the color of the liposomes lighter than the vitamins themselves, indicating effective encapsulation of vitamin components.

[0153] Odor: The liposomes in Examples 1-13 had no obvious odor, while Comparative Examples 1 and 4 had a slight phospholipid odor. This was due to the use of low-purity lecithin in the formulations and the absence of wall material. Higher lecithin purity results in a milder odor, making the liposomes more soluble in various end-product formulations and more readily accepted by consumers. Similarly, the addition of wall material encapsulates the liposomes, further masking the phospholipid odor. Adding a double-layer wall material further reduces the phospholipid odor and slows down phospholipid oxidation and vitamin degradation.

[0154] Encapsulation efficiency: The encapsulation efficiency of the liposomes in Examples 1-13 was all above 70%. The encapsulation efficiency is greatly affected by the product formulation and preparation process. For example, reducing the vitamin loading, increasing the phospholipid specifications, adding an appropriate amount of membrane stabilizer, adding wall material, and selecting appropriate homogenization parameters can all improve the encapsulation efficiency. For instance, compared with Example 4, Comparative Examples 7 and 8 had an improper ratio of membrane stabilizer to the phosphatidylcholine component in the phospholipid, which made the phospholipid bilayer structure unstable and prone to breakage, thus leading to a decrease in encapsulation efficiency. Comparing the encapsulation efficiency of the comparative examples with the corresponding examples, the differences in encapsulation efficiency caused by the formulation composition and the influence of homogenization parameters on the encapsulation efficiency can be clearly seen.

[0155] Particle size: The liposomes in Examples 1-13 all had a 40-mesh sieve pass rate of >99%, while the sieve pass rate of Comparative Example 4 was 90%, indicating that the product adhesion was relatively serious, which is consistent with the analysis results of the same state index.

[0156] Angle of repose: The angle of repose of a powder is an important parameter describing the packing characteristics of the powder in a static state, reflecting its flowability. The smaller the angle of repose, the better the flowability of the powder. The liposomes in Examples 1-13 have an angle of repose of about 40°, indicating very good flowability, while the angle of repose in Comparative Examples 1 and 4 increases, indicating relatively poorer flowability.

[0157] Solvent residue: This process can effectively remove the organic solvents used in the process. The solvent residue of the products in each example and comparative example is less than 50 ppm.

[0158] Rehydration particle size: After rehydration and dissolution, the average particle size of the liposomes in Examples 1-13 was less than 400 nm. Compared with Examples 10-13, the rehydration particle size was affected to some extent by the magnitude of the high-pressure homogenization pressure. The liposomes in Comparative Examples 1-11 showed a certain degree of increase in particle size compared with the corresponding examples, which also indicates that the particle size was affected by the formulation.

[0159] In addition, Comparative Example 1 used powdered sunflower phospholipid (PC20). Since the powdered phospholipid contains a large amount of ethanol-insoluble matter, chloroform was added during the dissolution process. It is not a processing aid permitted under GB2760, and therefore does not meet the conditions for industrialization in the food industry.

[0160] The evaluation results of the above indicators illustrate the necessity of selecting phospholipid specifications, the proportion of membrane stabilizers, the proportion of anhydrous ethanol, and the addition of wall materials.

[0161] The analysis of the above indicators only reflects the initial product level; therefore, further comparison of the acceleration stability of each group is needed. Effect Comparison Group 2: Acceleration Stability Examination

[0162] The liposome samples prepared in Examples 1-13 and Comparative Examples 1-11 were subjected to accelerated testing at 60°C to observe the product status and determine the vitamin retention rate. The results are shown in Table 6.

[0163] Retention rate: Vitamin content was measured initially and after 20 days of accelerated processing at 60℃. Retention rate = (Initial vitamin content - Vitamin content after accelerated processing) / Initial vitamin content * 100%. Table 6. Evaluation results of indicators after 20 days of liposome acceleration.

[0164] Sensory indicators: After 20 days of accelerated testing at 60℃, the liposomes in Comparative Examples 1, 2, 3, 4, 9, and 10 showed significantly accelerated browning and a distinct phospholipid oxidation odor. The reasons are as follows: Comparative Example 1 used low-purity lecithin, and the higher content of other components' phospholipids and glycolipids exacerbated oxidation. Comparative Examples 2 and 3 did not use a secondary wall material, and the single-layer wall material provided poor protection for the liposomes, leading to a certain degree of phospholipid oxidation. Even with the addition of an equal amount of wall material, Comparative Example 3 still experienced phospholipid oxidation. Comparative Example 4 did not use a secondary wall material for encapsulation, leaving the phospholipids directly exposed, accelerating the oxidative browning process. The reduced amount of antioxidant in Comparative Example 9 and the absence of antioxidants in Comparative Example 10 further intensified the oxidation process, resulting in browning and an unpleasant odor.

[0165] Encapsulation efficiency: The encapsulation efficiency of all products decreased to some extent after 20 days of acceleration. The reduction in liposome encapsulation efficiency in Examples 1-13 was less than 10%, while the encapsulation efficiency of samples in Comparative Examples 1-11 decreased significantly. The reasons are as follows: Comparative Example 1 used low-purity lecithin, which made the liposome structure more prone to leakage during acceleration; in Comparative Examples 2 and 3, only a single-layer wall material was used for liposome encapsulation, and the phospholipids also oxidized during acceleration, leading to a decrease in encapsulation efficiency; in Comparative Example 5, the ratio of one-layer to two-layer wall material was too high, resulting in poor encapsulation effect and a decrease in encapsulation efficiency; in Comparative Example 4, no wall material was used for encapsulation, which accelerated phospholipid oxidation and reduced the encapsulation effect. The encapsulation efficiency decreased in several ways. In Comparative Example 6, the lack of a membrane stabilizer accelerated content leakage. In Comparative Example 7, the low ratio of membrane stabilizer to phosphatidylcholine in phospholipids led to content leakage. In Comparative Example 8, the high ratio of membrane stabilizer to phosphatidylcholine in phospholipids resulted in excessive rigidity and content leakage. In Comparative Example 9, the reduced amount of antioxidant exacerbated phospholipid oxidation, leading to a decrease in encapsulation efficiency. In Comparative Example 10, the absence of antioxidants and phospholipid oxidation also resulted in a decrease in encapsulation efficiency. In Comparative Example 11, the high ratio of anhydrous ethanol in the alcohol phase to deionized water in the aqueous phase affected the encapsulation effect. Furthermore, compared to Examples 10-13, the lower high-pressure homogenization pressure resulted in a greater decrease in encapsulation efficiency, likely due to the lower degree of liposome homogenization leading to a decrease in vitamin encapsulation effectiveness.

[0166] Vitamin retention: After 20 days of accelerated treatment at 60°C, the vitamin retention rates of the liposomes in Examples 1-13 were all >95%. However, compared with the corresponding examples, the vitamin retention rates of Comparative Examples 1-11 were all lower, especially in Comparative Example 10, where the vitamin VA retention rate was only 92.0% due to the lack of added antioxidants, a significant decrease.

[0167] The above results of the accelerated stability test further illustrate the necessity of selecting the appropriate phospholipid specifications, adding wall materials, adding suitable stabilizers, adding antioxidants, and optimizing high-pressure homogenization parameters. (Effect Comparison Group 3: Application Performance Test)

[0168] The liposome samples prepared in Examples 2-6, 8 and Comparative Examples 1-11 were used to prepare tablet formulations, hard-shell capsules and solid beverages, respectively, and their application performance was investigated.

[0169] Tableting performance evaluation: The state and stability of the tablets were evaluated, and the results are shown in Table 7.

[0170] Hard-shell capsule evaluation: The feasibility of the process and the stability of the capsules were evaluated, and the results are shown in Table 8.

[0171] Dissolution performance evaluation: The dissolution rate and solution homogeneity were evaluated, and the results are shown in Table 9. Table 7. Results of liposome tableting performance evaluation.

[0172] Analysis of the data in Table 7 leads to the following conclusions:

[0173] High-purity phospholipids (such as soybean lecithin PC90 and above): help improve the chemical stability of the product and ensure that vitamins maintain a high retention rate in high-temperature accelerated stability tests. The vitamin retention rates of Examples 2-6 and 8 are all higher than 96%, while the retention rates of Comparative Example 1, which uses low-purity phospholipids, are slightly lower (VB6 95.8%, VB12 96.9%).

[0174] Adding appropriate wall material not only improves the physical stability of liposomes but also enhances their mechanical strength and pressure resistance during tableting, ensuring higher vitamin retention. Comparative Examples 2 and 3, with only one layer of wall material, resulted in vitamin retention rates decreasing to 95.0% and 95.5%, respectively; Comparative Example 5, with an excessively high ratio of one to two wall materials, resulted in a vitamin retention rate decreasing to 95.7%; and Comparative Example 4, without any wall material, resulted in a significant decrease in vitamin retention rate to 93.9%.

[0175] Membrane stabilizers: An appropriate ratio of membrane stabilizers enhances the structural stability of liposomes, preventing leakage of contents and thus improving vitamin retention. Comparative Example 6 lacked membrane stabilizers, resulting in a vitamin retention rate of 94.2%; Comparative Example 7 had an excessively low ratio of membrane stabilizer to phosphatidylcholine in the phospholipid, leading to a vitamin retention rate of 90.2%; Comparative Example 8 had an excessively high ratio of membrane stabilizer to phosphatidylcholine, also resulting in vitamin leakage and a retention rate of 92.1%.

[0176] Antioxidants play a crucial role in preventing the oxidative degradation of vitamins, especially in products containing easily oxidized fat-soluble vitamins (such as VA and VD). For example, Comparative Example 9 reduced the amount of antioxidants used, resulting in a decrease in the retention rates of VA and VD to 91.5% and 93.1%, respectively. Comparative Example 10 did not add any antioxidants, leading to a significant decrease in the retention rates of VA and VD to 90.8% and 91.3%, respectively.

[0177] The alcohol-to-water ratio directly affects the encapsulation effect of vitamins. In Comparative Example 11, the excessively high ratio of anhydrous ethanol in the alcohol phase to deionized water in the aqueous phase led to decreased liposome stability, with the retention rates of VC and VK significantly decreasing to 91.9% and 92.4%, respectively. Table 8. Performance evaluation results of liposome hard-shell capsules.

[0178] Analysis of the data in Table 8 leads to the following conclusions:

[0179] The importance of wall materials: Adding appropriate wall materials not only improves the fluidity of liposomes, ensuring the feasibility of hard-shell capsule production processes, but also enhances the physical stability of the product and prevents problems such as clumping and poor fluidity.

[0180] The impact of phospholipid purity: High-purity phospholipids help improve the chemical stability of products, especially in high-temperature accelerated stability tests. While low-purity phospholipids can achieve good results in some cases, high-purity phospholipids are the superior choice when considering other performance indicators.

[0181] The role of membrane stabilizers: An appropriate ratio of membrane stabilizers enhances the structural stability of liposomes, preventing leakage of contents and thus improving vitamin retention. An excessively high or low ratio of membrane stabilizers to phosphatidylcholine in phospholipids, or a lack of membrane stabilizers, will slightly reduce product stability.

[0182] The critical role of antioxidants: Antioxidants play a vital role in preventing the oxidative degradation of vitamins. This is especially true in products containing easily oxidized fat-soluble vitamins (such as vitamin A and vitamin D), where the addition of antioxidants is essential to ensure long-term stability.

[0183] Alcohol-to-water ratio: An appropriate ratio of anhydrous ethanol in the alcohol phase to deionized water in the aqueous phase can ensure the encapsulation effect of the product. An excessively high alcohol-to-water ratio will affect the vitamin retention rate of the product to some extent. Table 9. Results of liposome reconstitution performance evaluation.

[0184] Analysis of the data in Table 9 leads to the following conclusions:

[0185] The importance of phospholipid purity: High-purity phospholipids (such as soybean lecithin PC90 and above) help improve the dispersion speed and stability of liposomes and avoid slow dispersion caused by unstable phospholipid membrane structure.

[0186] The key role of wall material: Adding an appropriate amount of wall material can significantly improve the physical stability of liposomes and prevent them from flocculating during standing. This is very important for maintaining the long-term stability and consistency of the product. Compared with Example 3, Comparative Examples 2, 3, and 4 were only encapsulated with a single layer of wall material and without wall material encapsulation, respectively. Comparative Examples 2 and 3, although they could disperse and dissolve quickly, still showed slight flocculation, while Comparative Example 4 showed significantly worse dispersion and also exhibited flocculation. Although Comparative Example 5 was encapsulated with a double layer of wall material, slight flocculation still occurred due to the excessively high ratio of the first to second layer of wall material.

[0187] Effect of membrane stabilizers: Membrane stabilizers also play an important role in the physical stability of liposomes, and their ratio with the phosphatidylcholine component in phospholipids affects the long-term stability of the product to a certain extent. Compared with Example 6, Comparative Examples 7 and 8 reduced and increased the ratio of membrane stabilizer to phosphatidylcholine in phospholipids, respectively. Both dispersed more slowly and exhibited flocculation.

[0188] The effect of antioxidants: Although antioxidants have a relatively small impact on reconstitution performance, they play a key role in accelerated stability testing, ensuring the efficient retention of vitamin components.

[0189] Alcohol-to-water ratio: Adjusting the alcohol-to-water ratio appropriately can help ensure the encapsulation effect of liposomes, and also plays a role in the stability of the product and the retention of vitamins.

[0190] In summary, based on the performance evaluation results of liposomes, we analyzed their applicability for tableting, hard-shell capsules, and solid beverage applications.

[0191] Tableting Application: The liposomes in Examples 2-6 and 8 underwent tableting tests and stability studies, demonstrating that the process was feasible and the stability was satisfactory. The liposome processes in Comparative Examples 1-11 were feasible, but the tablets prepared in Comparative Examples 2-11 showed a significant decrease in retention rate after 20 days of accelerated processing. This was because the amount of wall material added, the proportion of membrane stabilizer, and the alcohol-water ratio were inappropriate. Without the protection of wall material and membrane stabilizer, the tablets were subjected to mechanical forces during compression, which to some extent damaged their structure, leading to a decrease in vitamin retention.

[0192] Hard-shell capsule application: All examples passed the test. The liposomes in Comparative Example 4 could not be used in hard-shell capsules because of their poor flowability and easy blockage of the outlet.

[0193] Application in solid beverages: The liposomes in Examples 2-6 and 8 dispersed and dissolved quickly and uniformly after reconstitution, with an average particle size below 310 nm, and remained homogeneous even after standing for 12 hours. However, the liposomes in Comparative Examples 4 and 6 dispersed more slowly, had larger particle sizes, and showed slight flocculation after standing for 12 hours. The reason for this was also the lack of added wall materials and membrane stabilizers. After the liposomes dissolved in water, the phospholipid membrane fused, leading to flocculation and making them unsuitable for use in solid beverages.

[0194] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A complex encapsulated vitamin liposome, characterized in that, It is prepared from the following raw materials in parts by weight: 2-65 parts vitamins, 15-65 parts phospholipids, 0.2-3 parts antioxidants, 1-8 parts film stabilizers, 9-45 parts first-layer wall material, and 4-20 parts second-layer wall material.

2. The composite encapsulated vitamin liposome according to claim 1, characterized in that, The vitamin is at least one of water-soluble vitamins or fat-soluble vitamins.

3. The composite encapsulated vitamin liposome according to any one of claims 1 or 2, characterized in that, The weight ratio of the water-soluble vitamin to the fat-soluble vitamin is (3-15):

1.

4. The composite encapsulated vitamin liposome according to any one of claims 1-3, characterized in that, The water-soluble vitamin is selected from one or more of vitamin C, vitamin B1, vitamin B2, vitamin B6, and vitamin B12; the fat-soluble vitamin is selected from one or more of vitamin A, vitamin D, vitamin E, vitamin K1, and vitamin K2.

5. The composite encapsulated vitamin liposome according to any one of claims 1-4, characterized in that, The phospholipid is selected from one or more of soybean lecithin, sunflower lecithin, and rapeseed lecithin; The phospholipid contains more than 60% acetone-insoluble matter. The phospholipid contains more than 50% phosphatidylcholine.

6. The composite encapsulated vitamin liposome according to any one of claims 1-5, characterized in that, The film stabilizer includes one or more of phytosterols, mono- and diglycerides of fatty acids, fatty acids, and vegetable oils; The melting points of the mono- and diglyceride fatty acid esters, fatty acids, and vegetable oils are 40-90℃.

7. The composite encapsulated vitamin liposome according to any one of claims 1-6, characterized in that, The weight ratio of the film stabilizer to the phosphatidylcholine component in the phospholipid is 1:3 to 1:

15.

8. The composite encapsulated vitamin liposome according to any one of claims 1-7, characterized in that, The phytosterols are selected from one or more of sitosterol, stigmasterol, rapeseed sterol, ergosterol, and microalgesterol.

9. The composite encapsulated vitamin liposome according to any one of claims 1-8, characterized in that, The antioxidant is selected from one or more of ascorbic acid, ascorbate palmitate, mixed tocopherols, citrus flavonoids, proanthocyanidins, tea polyphenols, and carotenoids.

10. The composite encapsulated vitamin liposome according to any one of claims 1-9, characterized in that, The first layer of wall material includes one or more of modified starch, gum arabic, maltodextrin, resistant dextrin, maltodextrin, and isomaltodextrin.

11. The composite encapsulated vitamin liposome according to any one of claims 1-9, characterized in that, The second-layer wall material includes one or more of hydroxypropyl methylcellulose, hydroxypropyl ethylcellulose, methylcellulose, ethylcellulose, carboxymethylcellulose, and sodium carboxymethylcellulose.

12. The composite encapsulated vitamin liposome according to any one of claims 1-11, characterized in that, The weight ratio of the first layer of wall material to the second layer of wall material is (1-5):

1.

13. The method for preparing the composite encapsulated vitamin liposomes according to any one of claims 1-12, comprising the following steps: S1. Aqueous phase preparation: Prepare a water-soluble vitamin aqueous solution; S2. Alcohol phase preparation: After thoroughly mixing and dissolving anhydrous ethanol, the phospholipid, and the film stabilizer, add the fat-soluble vitamin until completely dissolved; S3. Preparation of wall material solution: Prepare one layer of wall material solution and two layers of wall material solution respectively; S4. Slowly inject the alcohol phase into the aqueous phase, stir thoroughly to form a primary liposome dispersion solution, concentrate under reduced pressure to obtain a concentrated solution, slowly add it to the wall material solution obtained in step S3, stir thoroughly to form a composite encapsulated liposome dispersion solution. as well as S5. The composite encapsulated liposome dispersion solution obtained in step S4 is subjected to high-speed shearing and high-pressure homogenization. The homogenized layer of encapsulated liposome dispersion solution is mixed with the second layer of wall material solution and then dried to obtain the composite encapsulated vitamin liposome.

14. The method according to claim 13, characterized in that, In step S3, the solid content of the first layer wall material solution is 20-60 wt%, and the solid content of the second layer wall material solution is 1-10 wt%.

15. The method according to any one of claims 13-14, characterized in that, In step S4, the weight ratio of water to alcohol is (1-8):

1.

16. The method according to any one of claims 13-15, characterized in that, In step S5, the homogenized layer of embedded liposome dispersion solution and the second layer of wall material solution are mixed by a two-phase nozzle mixing method.

17. The method according to any one of claims 13-16, characterized in that, In step S5, the drying method is selected from at least one of spray drying, low-temperature spray drying, freeze drying, or freeze spray drying.

18. The method according to any one of claims 13-17, characterized in that, In step S5, the feed nozzle matched with the drying tower used for drying is a three-fluid coaxial two-phase nozzle.

19. The application of the composite encapsulated vitamin liposome as described in any one of claims 1-12, including the preparation of tablets, hard-shell capsules, and solid beverages.

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