Lutein ester flash release tablet for relieving visual fatigue and preparation method thereof

Abstract

The present application relates to a kind of lutein ester flash release tablets for relieving visual fatigue and its preparation method.The flash release tablet includes lutein ester porous dry granules, mannitol-erythritol complex sugar alcohol, crosslinked polyvinylpyrrolidone, silicified microcrystalline cellulose and sodium stearate fumarate;The porous dry granules include oil phase containing lutein ester, octenyl succinate modified porous starch, zein, tannic acid, low ester pectin, trehalose-mannitol freeze-drying protective agent and L-leucine, oil phase is at least partially located in modified porous starch channel and surface, and by zein, tannic acid and low ester pectin to form composite interface stabilizing component.The present application is prepared by oil phase, shear emulsification, high-pressure homogenization, low-temperature atomization freeze-drying and tableting, has good disintegration, redispersion and stability, and can be used for preparing food, health food or nutritional supplement for relieving visual fatigue.

Description

Technical Field

[0001] This invention relates to the field of functional formulation technology, and in particular to a lutein ester flash-release tablet for relieving visual fatigue and its preparation method. Background Technology

[0002] With the increasing frequency of use of electronic display devices, prolonged close-range eye use, screen light stimulation, and unstable eye environments can easily cause problems such as dry eyes, soreness, blurred vision, and visual fatigue. Lutein esters, as a fat-soluble carotenoid, are often used in eye health-related foods, health supplements, or nutritional supplements, and have good application value. However, lutein esters have poor water solubility and are quite sensitive to environmental factors such as light, oxygen, and heat. When used directly in tablets, granules, or other solid dosage forms, they are prone to problems such as uneven dispersion, slow dissolution, oil phase precipitation, and insufficient storage stability.

[0003] To improve the application performance of lutein esters, existing technologies have proposed various formulations such as microencapsulation, emulsified powder, solid dispersion, orally disintegrating tablets, and effervescent tablets to enhance their processing adaptability, ease of administration, or water dispersibility. However, existing lutein ester microencapsulated powders or ordinary emulsified powders mainly focus on conventional encapsulation and emulsification dispersion, while ordinary orally disintegrating tablets or flash-release tablets primarily rely on sugar alcohols, disintegrants, and lubricants to achieve rapid tablet disintegration. Although these methods can improve the taste and disintegration rate to some extent, there is still room for improvement in the redispersibility stability of the lutein ester oil phase after rapid tablet disintegration, the inhibition of oil droplet aggregation, and the protection of heat-sensitive active ingredients during the drying process.

[0004] Therefore, how to ensure rapid disintegration and good formability of lutein ester flash-release tablets while maintaining good redispersibility of the lutein ester oil phase in water after disintegration, and how to improve its stability during preparation and storage, have become technical problems that need to be further solved in the development of lutein ester solid dosage forms. Summary of the Invention

[0005] To address the aforementioned problems in the prior art, this invention provides a lutein ester flash-release tablet for relieving visual fatigue and its preparation method.

[0006] To achieve the above objectives, this invention provides a lutein ester flash-release tablet, comprising, by weight, the following components: 15-45% porous dry lutein ester particles, 40-75% mannitol-erythritol complex sugar alcohol, 3-10% crospovidone, 2-10% silanized microcrystalline cellulose, and 0.2-1.0% sodium stearate fumarate. The porous dry lutein ester particles serve as the active loading unit, the mannitol-erythritol complex sugar alcohol serves as the soluble backbone and taste-improving component, crospovidone serves as the disintegration-promoting component, the silanized microcrystalline cellulose serves as the compressibility and water absorption-improving component, and the sodium stearate fumarate serves as the lubricating component. The combination of these components ensures tablet formability while allowing the tablet to quickly absorb water and disintegrate upon ingestion, releasing the porous dry lutein ester particles.

[0007] Further, based on the total mass of the lutein ester porous dry particles, the lutein ester porous dry particles comprise: 10-30% oil phase containing lutein ester, 8-25% octenyl succinate-modified porous starch, 2-10% zein, 0.1-2.0% tannic acid, 0.5-6% low-ester pectin, 30-70% trehalose-mannitol freeze-drying protectant, and 0.2-2.5% L-leucine. The oil phase containing lutein esters is used to dissolve and disperse lutein esters; octenyl succinate-modified porous starch has a porous structure and amphiphilic modifying groups, which can adsorb and load the oil phase containing lutein esters and participate in oil-water interface stability; zein, tannic acid, and low-ester pectin can be used together as composite interface stabilizing components. When used in conjunction with octenyl succinate-modified porous starch, it is beneficial to improve the dispersion stability of the oil phase containing lutein esters during emulsification, drying, and rehydration, and reduce the risk of oil phase aggregation, leakage, or floating; trehalose-mannitol freeze-drying protectant is used to maintain the droplet and particle structure during freeze-drying, forming a porous framework that facilitates rapid rehydration; L-leucine is used to improve the flowability, dispersibility, and anti-adhesion of freeze-dried particles.

[0008] Furthermore, the lutein ester-containing oil phase is at least partially located in the channels and surface of the octenyl succinate-modified porous starch, and the lutein ester porous dry particles have a composite interfacial stabilizing component composed of zein, tannic acid, and low-ester pectin. Through this structure, the lutein ester oil phase does not exist solely as ordinary oil droplets or ordinary microcapsules, but is simultaneously supported by the modified porous starch channels and stabilized by the composite interfacial stabilizing component, making it less prone to significant aggregation or precipitation during tablet disintegration and hydration, thus maintaining a better redispersibility.

[0009] Furthermore, the oil phase containing lutein esters comprises lutein esters, medium-chain triglycerides, phospholipids, and vitamin E polyethylene glycol succinate. The mass ratio of lutein esters to medium-chain triglycerides is 1:3 to 1:15, the mass ratio of lutein esters to phospholipids is 1:0.2 to 1:1.5, and the mass ratio of lutein esters to vitamin E polyethylene glycol succinate is 1:0.05 to 1:0.8. Medium-chain triglycerides, acting as an oil phase carrier, improve the solubility and dispersion of lutein esters in the oil phase; phospholipids assist in the formation of an interfacial layer and improve the emulsion state; vitamin E polyethylene glycol succinate has both solubilizing and antioxidant effects, which helps improve the stability of the oil phase system.

[0010] Furthermore, the octenyl succinate-modified porous starch has a degree of substitution of 0.005–0.020, an average pore size of 0.5–30 μm, and an oil absorption value of 0.8–3.5 g / g. If the substitution is too low, the modified porous starch will have insufficient hydrophobicity and interfacial stability; if the substitution is too high, it may affect its dispersibility in water and its suitability for food applications. The aforementioned pore size and oil absorption value range facilitate the entry of the lutein ester-containing oil phase into the porous structure and achieve stable loading, while avoiding excessive oil phase leakage.

[0011] Furthermore, the mass ratio of zein, tannic acid, and low-ester pectin is 1:0.03–0.4:0.2–1.5. This ratio range is beneficial for stabilizing the composite interface. If the amount of tannic acid is too low, its strengthening effect on the zein interface film will be insufficient; if the amount of tannic acid is too high, it may lead to excessive aggregation of composite particles. If the amount of low-ester pectin is too low, the interfacial hydrophilicity and dispersion stability will be insufficient; if the amount of low-ester pectin is too high, it may increase the viscosity of the system and affect the emulsification and atomization processes.

[0012] Furthermore, in the trehalose-mannitol freeze-drying protectant, the mass ratio of trehalose to mannitol is 1:0.5 to 1:4. Trehalose can protect the emulsion droplet interface and active ingredients during freeze-drying, while mannitol can form a better freeze-dried framework and particle morphology. The combination of the two is beneficial for obtaining porous dry particles with good rehydration properties and mechanical stability.

[0013] Furthermore, the porous dry particles of lutein ester have a porosity of 35-85%, and after redispersement in water, they form droplets with a D90 of no more than 600 nm. This porosity range facilitates rapid water absorption and rehydration of the particles, while the limited D90 indicates that the porous dry particles have good redispersibility in water, which helps reduce the risk of oil phase aggregation and floating of lutein ester.

[0014] Furthermore, in the mannitol-erythritol complex, the mass ratio of mannitol to erythritol is 1:0.2 to 1:2. Mannitol has a good taste and compressibility, while erythritol has a refreshing taste and good water solubility. The combination of the two is beneficial for improving the mouthfeel, water absorption and dispersibility, and tablet forming performance.

[0015] Furthermore, the lutein ester flash-release tablets also include 0.1% to 3% of a flavoring agent. The flavoring agent may be selected from one or more of sucralose, steviol glycosides, mogrosides, citric acid, malic acid, peppermint flavor, and blueberry flavor. The addition of the flavoring agent can improve the slight oiliness, astringency, or herbal odor that may be caused by the lutein ester oil phase and polyphenolic components, thereby improving patient compliance.

[0016] This invention also provides a method for preparing the above-mentioned lutein ester flash-release tablets, comprising the following steps: dispersing porous starch in water, adjusting the pH to 7.5-9.0, adding octenyl succinic anhydride, reacting at 20-45°C for 1-6 hours, washing and drying to obtain octenyl succinate-modified porous starch; dissolving lutein ester in an oil phase containing medium-chain triglycerides, phospholipids and vitamin E polyethylene glycol succinate to obtain an oil phase containing lutein ester; dispersing octenyl succinate-modified porous starch and low-ester pectin in an aqueous phase, adding the oil phase containing lutein ester, and shearing and emulsifying at 8000-18000 rpm for 2-8 minutes at 20-35°C to obtain a crude emulsion; dissolving zein and tannins in... The crude emulsion is added to an ethanol-water solution with a volume fraction of 60-85%, and the pH of the system is adjusted to 4.0-5.5. The mixture is then homogenized under high pressure at 40-80 MPa for 2-5 cycles, with the material temperature not exceeding 45°C during homogenization, to obtain a lutein ester emulsion. Trehalose, mannitol, and L-leucine are added to the lutein ester emulsion, and the solid content is adjusted to 10-30%. The mixture is then atomized in a freezing medium at -40°C to -196°C to form frozen particles, which are then freeze-dried to obtain porous dry lutein ester particles. These porous dry lutein ester particles are mixed with mannitol-erythritol complex sugar alcohol, crospovidone, silicified microcrystalline cellulose, sodium stearate fumarate, and a flavoring agent, and then compressed into tablets to obtain the lutein ester flash-release tablets.

[0017] Furthermore, the ethanol-water solution described in S4 is mainly used to dissolve or disperse zein and tannic acid. During the subsequent low-temperature atomization freezing and freeze-drying process, the ethanol in the system can be removed along with the water during the vacuum drying stage. Preferably, the freeze-drying includes primary drying and secondary drying, with the secondary drying used to further reduce the moisture and ethanol residue in the porous dry lutein ester particles. The residual ethanol content in the resulting porous dry lutein ester particles is preferably controlled below 0.5%.

[0018] Furthermore, in the preparation method, shear emulsification is used to initially disperse the oil phase containing lutein esters in an aqueous phase containing octenyl succinate-modified porous starch and low-ester pectin, ensuring sufficient contact between the oil phase and the modified porous starch and promoting the oil phase's entry into the pores and surface of the porous starch. Subsequently, an ethanol-water solution containing zein and tannic acid is added, and high-pressure homogenization is performed at pH 4.0–5.5, which promotes the formation of a composite interfacial stabilizing component by zein, tannic acid, and low-ester pectin around the oil droplets and the surface of the modified porous starch. Controlling the pressure, number of cycles, and temperature during high-pressure homogenization helps reduce droplet size, improve interfacial layer uniformity, and reduce the risk of lutein ester degradation under high shear and temperature rise conditions. Low-temperature atomization freezing and freeze-drying help avoid the adverse effects of conventional high-temperature drying on lutein esters, while forming dry particles with high porosity, improving their rehydration and redispersibility in water.

[0019] The present invention also provides the use of the lutein ester flash-release tablets in the preparation of food, health food or nutritional supplements for relieving visual fatigue.

[0020] Compared with the prior art, the present invention provides a lutein ester flash-release tablet for relieving visual fatigue and a method for preparing the same, which has the following beneficial effects: 1. This invention utilizes octenyl succinate-modified porous starch to load an oil phase containing lutein esters, allowing at least a portion of the oil phase to enter the pores and surface of the modified porous starch. The porous structure and amphiphilic characteristics of the modified porous starch enhance the carrying capacity and dispersion stability of the oil phase. Compared to ordinary lutein ester powder or conventional microcapsule powder, this structure helps reduce extravasation, aggregation, or floating of the lutein ester oil phase during tablet compression, storage, and rehydration.

[0021] 2. This invention utilizes zein, tannic acid, and low-ester pectin as composite interface stabilizing components, and combines them with octenyl succinate-modified porous starch to stabilize the dispersion of the lutein ester-containing oil phase. The combination of these three components improves the redispersibility of porous dry lutein ester particles in water, resulting in a smaller and more uniform dispersion system after tablet disintegration, thereby reducing the risk of lutein ester oil phase aggregation, precipitation, or floating.

[0022] 3. This invention employs a low-temperature atomization freeze-drying process using trehalose-mannitol freeze-drying protectant and L-leucine, which reduces the adverse effects of high-temperature drying on lutein esters and forms porous dry particles with a certain porosity and good rehydration properties. When these porous dry particles are combined with mannitol-erythritol complex sugar alcohols, crospovidone, silicified microcrystalline cellulose, and sodium stearate fumarate, lutein ester flash-release tablets with good formability, good disintegration upon ingestion, and a pleasant taste can be obtained. These tablets are suitable for preparing foods, health foods, or nutritional supplements for relieving visual fatigue. Attached Figure Description

[0023] Figure 1 This is a process flow diagram of the preparation method of lutein ester flash release tablets of the present invention. Detailed Implementation

[0024] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] Unless otherwise stated, all raw materials used in this embodiment are food-grade or pharmaceutical excipient-grade raw materials, all percentages are by mass, and the water is purified water. In this embodiment, the freeze-drying process includes primary drying and secondary drying. The secondary drying is used to further reduce the moisture and residual ethanol in the porous dry lutein ester particles. The lutein ester uses lutein ester raw material with a lutein dipalmitate content of not less than 80%; the medium-chain triglyceride is caprylic / capric triglyceride; the phospholipid is soybean phospholipid; the vitamin E polyethylene glycol succinate is TPGS; the porous starch is commercially available corn-derived porous starch with an average pore size of 0.5–30 μm; and the degree of esterification of the low-ester pectin is 30–45%. Example

[0026] Based on 100g of porous dry lutein ester granules, the following components were weighed: 20.0g of oil phase containing lutein ester, 18.0g of octenyl succinate-modified porous starch, 6.0g of zein, 1.0g of tannic acid, 3.0g of low-ester pectin, 51.0g of trehalose-mannitol freeze-drying protectant, and 1.0g of L-leucine. The trehalose-mannitol freeze-drying protectant consisted of 17.0g of trehalose and 34.0g of mannitol, with a mass ratio of trehalose to mannitol of 1:2. The oil phase containing lutein ester consisted of lutein ester, medium-chain triglycerides, phospholipids, and vitamin E polyethylene glycol succinate, with a mass ratio of 1:8:0.8:0.2.

[0027] In the preparation process, porous starch was dispersed in water, the pH was adjusted to 8.2, octenyl succinic anhydride was added, and the reaction was carried out at 35°C for 3 hours. After the reaction, the starch was washed and dried to obtain octenyl succinate-modified porous starch with a degree of substitution of 0.012. Lutein esters were added to medium-chain triglycerides and dissolved by stirring at 45°C under light-protected and nitrogen-protected conditions. Phospholipids and vitamin E polyethylene glycol succinate were then added to obtain an oil phase containing lutein esters. Octenyl succinate-modified porous starch and low-ester pectin were dispersed in an aqueous phase, and the above oil phase containing lutein esters was added. The mixture was sheared and emulsified at 12000 rpm for 5 minutes at 30°C to obtain a crude emulsion. Zead protein and tannic acid were dissolved in a 75% (v / v) aqueous ethanol solution and added to the crude emulsion. The pH of the system was adjusted to 4.8, and then the mixture was homogenized three times under high pressure at 60 MPa, with the material temperature controlled not to exceed 40°C during homogenization, to obtain a lutein ester emulsion. Trehalose, mannitol, and L-leucine were added to the lutein ester emulsion to adjust the solid content to 20%. The mixture was then atomized in a -80°C freezing medium to form frozen particles. After freeze-drying, the water content was reduced to no more than 5%, and the residual ethanol was further reduced by secondary drying to obtain porous dry lutein ester particles.

[0028] Based on the total mass of 100g of lutein ester flash-release tablets, weigh out 30.0g of the above-mentioned porous dry lutein ester granules, 54.0g of mannitol-erythritol complex sugar alcohol, 6.0g of crospovidone, 8.0g of siliconized microcrystalline cellulose, 0.6g of sodium stearate fumarate, and 1.4g of flavoring agent. The mannitol-erythritol complex sugar alcohol has a mass ratio of mannitol to erythritol of 1:1, and the flavoring agent consists of sucralose, citric acid, and blueberry flavoring in a mass ratio of 1:3:2. After mixing all components evenly, compress the tablets at a pressure of approximately 5kN to obtain lutein ester flash-release tablets, with a single tablet weighing 500mg. Example

[0029] Based on 100g of porous dry lutein ester granules, the composition includes: 30.0g of oil phase containing lutein ester, 25.0g of octenyl succinate-modified porous starch, 10.0g of zein, 2.0g of tannic acid, 2.8g of low-ester pectin, 30.0g of trehalose-mannitol freeze-drying protectant, and 0.2g of L-leucine. The mass ratio of trehalose to mannitol is 1:0.5. In the oil phase containing lutein ester, the mass ratio of lutein ester, medium-chain triglycerides, phospholipids, and vitamin E polyethylene glycol succinate is 1:15:1.5:0.3.

[0030] In the preparation process, in step S1, the pH was adjusted to 9.0, and the reaction was carried out at 45℃ for 6 hours to obtain octenyl succinate-modified porous starch with a degree of substitution of 0.020; in step S3, the starch was sheared and emulsified at 18000 rpm for 8 minutes at 35℃; in step S4, zein and tannic acid were dissolved in an 85% (v / v) ethanol aqueous solution, the pH of the system was adjusted to 5.5, and the starch was homogenized five times under high pressure at 80 MPa, with the material temperature controlled not to exceed 45℃ during the homogenization process; in step S5, the solid content was adjusted to 30%, and the starch was atomized in a -40℃ freezing medium to form frozen particles, which were then freeze-dried to obtain lutein ester porous dry particles.

[0031] Based on the total mass of 100g of lutein ester flash-release tablets, the following components were used: 45.0g porous dry lutein ester granules, 40.0g mannitol-erythritol complex sugar alcohol, 10.0g crospovidone, 2.0g silanized microcrystalline cellulose, 0.2g sodium stearate fumarate, and 2.8g flavoring agent. The mass ratio of mannitol to erythritol was 1:0.2. The remaining preparation steps were the same as in Example 1. Example

[0032] Based on 100g of porous dry lutein ester granules, the oil phase containing lutein ester is 16.9g, octenyl succinate-modified porous starch is 8.0g, zein is 2.0g, tannic acid is 0.1g, low-ester pectin is 0.5g, trehalose-mannitol freeze-drying protectant is 70.0g, and L-leucine is 2.5g. The mass ratio of trehalose to mannitol is 1:4. In the oil phase containing lutein ester, the mass ratio of lutein ester, medium-chain triglycerides, phospholipids, and vitamin E polyethylene glycol succinate is 1:3:0.2:0.05.

[0033] In the preparation process, in step S1, the pH was adjusted to 7.5, and the reaction was carried out at 20°C for 1 hour to obtain octenyl succinate-modified porous starch with a degree of substitution of 0.005; in step S3, the starch was sheared and emulsified at 8000 rpm for 2 minutes at 20°C; in step S4, zein and tannic acid were dissolved in a 60% (v / v) ethanol aqueous solution, the pH of the system was adjusted to 4.0, and the starch was homogenized twice under high pressure at 40 MPa, with the material temperature controlled not to exceed 35°C during homogenization; in step S5, the solid content was adjusted to 10%, and the starch was atomized in a -196°C freezing medium to form frozen particles, which were then freeze-dried to obtain lutein ester porous dry particles.

[0034] Based on the total mass of 100g of lutein ester flash-release tablets, the following components were used: 15.0g porous dry lutein ester granules, 75.0g mannitol-erythritol complex sugar alcohol, 3.0g crospovidone, 6.7g silanized microcrystalline cellulose, 0.2g sodium stearate fumarate, and 0.1g flavoring agent. The mass ratio of mannitol to erythritol was 1:2. The remaining preparation steps were the same as in Example 1. Example

[0035] Based on 100g of porous dry lutein ester granules, the oil phase containing lutein ester is 10.0g, octenyl succinate-modified porous starch is 20.0g, zein is 4.0g, tannic acid is 1.6g, low-ester pectin is 6.0g, trehalose-mannitol freeze-drying protectant is 56.2g, and L-leucine is 2.2g. The mass ratio of trehalose to mannitol is 1:3. In the oil phase containing lutein ester, the mass ratio of lutein ester, medium-chain triglycerides, phospholipids, and vitamin E polyethylene glycol succinate is 1:6:0.8:0.8. During preparation, in step S1, the pH was adjusted to 8.0 and the reaction was carried out at 30℃ for 4 hours; in step S3, the mixture was sheared and emulsified at 10,000 rpm at 25℃ for 4 minutes; in step S4, the pH of the system was adjusted to 4.5 and homogenized under high pressure at 50 MPa three times; in step S5, the solid content was adjusted to 15%, and the mixture was atomized in a freezing medium at -100℃ to form frozen particles, which were then freeze-dried to obtain porous dry particles of lutein ester.

[0036] Based on the total mass of 100g lutein ester flash-release tablets, the following components are included: 20.0g porous dry lutein ester granules, 60.0g mannitol-erythritol complex sugar alcohol, 8.0g crospovidone, 10.0g silanized microcrystalline cellulose, 1.0g sodium stearate fumarate, and 1.0g flavoring agent. The mass ratio of mannitol to erythritol is 1:1.5. The remaining preparation steps are the same as in Example 1.

[0037] Comparative Example 1 This comparative example is basically the same as Example 1, except that the octenyl succinate modified porous starch in Example 1 is replaced with an equal amount of unmodified porous starch. The other components, amounts and preparation steps are the same as in Example 1.

[0038] Comparative Example 2 This comparative example is essentially the same as Example 1, except that zein, tannic acid, and low-ester pectin are not added, and the reduced mass is compensated for by the trehalose-mannitol freeze-drying protectant. Specifically, based on 100g of porous dry lutein ester particles, the composition includes 20.0g of lutein ester oil phase, 18.0g of octenyl succinate-modified porous starch, 61.0g of trehalose-mannitol freeze-drying protectant, and 1.0g of L-leucine. The remaining preparation steps are the same as in Example 1.

[0039] Comparative Example 3 This comparative example is basically the same as Example 1, except that in S5, low-temperature atomization freeze drying is not used; instead, conventional spray drying is used to prepare dry particles. The spray drying inlet temperature is 130°C and the outlet temperature is 70°C. The remaining components, amounts, and preparation steps are the same as in Example 1.

[0040] Comparative Example 4 This comparative example uses tablets made from ordinary lutein ester microcapsule powder. Based on 100g of microcapsule powder, the powder contains 20.0g of lutein ester oil phase, 35.0g of maltodextrin, 20.0g of ordinary octenyl succinic acid starch, 10.0g of gum arabic, 14.0g of trehalose, and 1.0g of magnesium stearate. The ordinary lutein ester microcapsule powder was prepared using a conventional emulsification and spray drying method. Tableting was then performed according to the tablet excipient ratio in Example 1.

[0041] Test methods 1. Particle size D90 determination method: Take 0.10 g of porous dry lutein ester granules, add them to 100 mL of purified water, and stir at 300 rpm for 2 min at 25℃ to obtain a granule redispersible solution. Separately, take one lutein ester flash-release tablet, add it to 200 mL of purified water at 37℃, and stir at 100 rpm until completely disintegrated. Take the disintegration liquid as the tablet disintegration dispersion. Use a laser particle size analyzer to determine the particle size distribution of the above granule redispersible solution and the tablet disintegration dispersion, and record the D90 value.

[0042] 2. Porosity determination method: Take an appropriate amount of porous dry lutein ester particles and determine their true density ρt using a helium true density meter; take a certain mass of sample and place it in a graduated cylinder, gently tap it until the volume basically no longer changes, and calculate the apparent density ρa. Calculate the porosity using the following formula: Porosity = (1 - ρa / ρt) × 100%.

[0043] 3. Tablet disintegration time limit test method: Take 6 tablets of lutein ester flash release tablets, use purified water at 37℃±1℃ as the medium, and perform the test according to the apparatus and operation method of the disintegration time limit test method in General Chapter 0921 of the Chinese Pharmacopoeia. Record the time required for each sample to completely disintegrate without obvious hard core residue, and take the average value as the disintegration time limit.

[0044] 4. Tablet Friability Test Method: Take several lutein ester flash-release tablets, remove surface powder, weigh accurately, place in a tablet friability tester, rotate 100 times at 25 rpm, remove, remove any loose powder, and weigh again. Calculate the percentage of weight loss. The friability test shall be performed according to the Tablet Friability Test Method in General Chapter 0923 of the Chinese Pharmacopoeia.

[0045] 5. Method for determining lutein ester content and accelerated stability: Take a sample of lutein ester flash release tablets, grind and mix them thoroughly. Weigh an appropriate amount of sample under light-protected conditions. After extraction with organic solvents and necessary saponification treatment, determine the lutein-related content using high-performance liquid chromatography (HPLC) and calculate the lutein ester content. Sample pretreatment and detection conditions should refer to the HPLC determination method in GB 5009.248 "National Food Safety Standard - Determination of Lutein in Food". During the accelerated stability test, place the sample under the conditions of 40℃±2℃ and 75%±5% relative humidity, store it away from light for 30 days, measure the content of xanthophyll ester in the sample at 0 day and 30 day respectively, and calculate the retention rate of xanthophyll ester according to the following formula: Xanthophyll ester retention rate = (xanthophyll ester content at 30 day / xanthophyll ester content at 0 day) × 100%.

[0046] 6. Method for determining the micellar phase transfer rate of xanthophyll ester after simulated gastrointestinal digestion: Take a xanthophyll ester fast-disintegrating tablet sample equivalent to 10 mg of xanthophyll ester, grind it into fine powder, add simulated saliva, and treat at 37℃ for 2 min; then add simulated gastric juice, adjust pH to 2.0, and treat with oscillation at 37℃ for 2 h; then add simulated intestinal fluid containing bile salt, pancreatin and calcium ions, adjust pH to 6.8, and treat with oscillation at 37℃ for 2 h. After digestion, centrifuge at 10000 g for 30 min, take the supernatant micellar phase, extract with organic solvent under dark condition, then determine the xanthophyll-related content by high performance liquid chromatography, and convert to the xanthophyll ester content. Calculate the micellar phase transfer rate according to the following formula: Micellar phase transfer rate = (converted xanthophyll ester content in micellar phase / total added amount of xanthophyll ester in sample) × 100%.

[0047] 7. Evaluation method for the effect of xanthophyll ester fast-disintegrating tablets in relieving visual fatigue: Select 90 subjects who have long-term use of electronic display devices and have visual fatigue symptoms, randomly divide them into a blank control group, a common microencapsulated powder tablet group and a test food group, with 30 cases in each group. The test food group takes the xanthophyll ester fast-disintegrating tablet prepared in Example 1 daily; the common microencapsulated powder tablet group takes the common xanthophyll ester microencapsulated powder tablet prepared in Comparative Example 4 daily, and the intake of xanthophyll ester is the same as that of the test food group; the blank control group takes blank tablets with basically the same appearance and taste but no xanthophyll ester daily. Each group takes the product continuously for 30 days. Before and after the test food intervention, eye symptom score, clear vision persistence and distant vision examination are performed respectively, and adverse reactions are recorded. Eye symptoms include eye distension, eye soreness, photophobia, blurred vision, dry eyes, foreign body sensation and lacrimation, which are scored according to none, mild, moderate and severe; clear vision persistence is measured by a "pin"-shaped three-dimensional block diagram, and the percentage of clear vision time in the total fixation time is calculated.

[0048] Test Results

[0049]

[0050]

[0051] Note: The lower the total symptom score, the milder the visual fatigue symptoms; the higher the clear vision persistence, the better the ability of sustained clear fixation.

[0052] Result Analysis Table 1 shows that the D90 of the porous dry lutein ester particles obtained in Example 1 after redispersement in water is 236 nm, and the D90 of the tablet disintegration solution is 268 nm. The lutein ester retention rate after 30 days is 93.4%, and the micelle phase transfer rate is 56.2%, all of which are superior to Examples 2-4 and the comparative examples. This indicates that under optimal formulation and process conditions, the present invention can effectively maintain the fine dispersion state of the lutein ester oil phase and improve its storage stability and micelle phase transfer ability in a simulated digestive environment. Examples 2-4 all fall within the scope of the present invention, and their particle redispersibility D90 and tablet disintegration solution D90 are all no greater than 600 nm, indicating that the technical solution of the present invention is feasible under different formulations and process parameters.

[0053] Compared with Example 1, in Comparative Example 1, replacing the octenyl succinate-modified porous starch with unmodified porous starch significantly increased the redispersible particle size; in Comparative Example 2, removing zein, tannic acid, and low-ester pectin significantly increased the particle redispersibility D90 and disintegration D90, while decreasing the lutein ester retention rate and micelle phase transfer rate, indicating that the combination of the above three components helps improve the interfacial stability of the lutein ester oil phase and its redispersibility in water; in Comparative Example 3, conventional spray drying resulted in decreased porosity and increased redispersible particle size; and in Comparative Example 4, tableting with ordinary lutein ester microcapsule powder resulted in the worst overall performance.

[0054] As shown in Table 2, Examples 1-4 all exhibit suitable porosity, short disintegration time, and low friability, indicating that the lutein ester flash-release tablets obtained in this invention have good rehydration disintegration performance and tablet mechanical stability. Although Comparative Example 2 has a shorter disintegration time, its redispersible particle size, lutein ester retention rate, and micelle phase transfer rate are significantly inferior to those of the Examples, indicating that simply having faster disintegration does not necessarily mean that the lutein ester oil phase has good redispersibility.

[0055] As shown in Table 3, after consuming the lutein ester flash-release tablets prepared in Example 1 for 30 days, the total symptom score of the test group decreased, the average improvement in visual persistence was 15.4%, and the improvement rate of subjective symptoms of visual fatigue was 70.0%, with no abnormal changes in distance vision or significant adverse reactions observed. The ordinary microcapsule powder tablet group also showed some improvement, but its improvement rate in visual persistence and the improvement rate of subjective symptoms of visual fatigue were lower than those of the test group, indicating that the lutein ester flash-release tablets of this invention have a better application effect in relieving visual fatigue.

[0056] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A lutein ester flash-release tablet for relieving visual fatigue, characterized in that, Based on the total mass of the lutein ester flash-release tablets, it comprises the following components: Lutein ester porous dry granules 15-45%; mannitol-erythritol complex sugar alcohol 40-75%; crospovidone 3-10%; silicified microcrystalline cellulose 2-10%; Sodium stearate 0.2-1.0%; The lutein ester porous dry particles, based on their total mass, comprise: 10-30% oil phase containing lutein ester; 8-25% octenyl succinate-modified porous starch; 2-10% zein; 0.1-2.0% tannins; 0.5-6% low-ester pectin; 30-70% trehalose-mannitol freeze-drying protectant; and 0.2-2.5% L-leucine. The oil phase containing lutein esters is at least partially located in the channels and surface of the octenyl succinate-modified porous starch, and the porous dry particles of lutein esters have a composite interfacial stabilizing component composed of zein, tannic acid and low-ester pectin.

2. The lutein ester flash-release tablet according to claim 1, characterized in that, The oil phase containing lutein esters includes lutein esters, medium-chain triglycerides, phospholipids, and vitamin E polyethylene glycol succinate. The mass ratio of lutein ester to medium-chain triglycerides is 1:3 to 1:15; the mass ratio of lutein ester to phospholipids is 1:0.2 to 1:1.5; and the mass ratio of lutein ester to vitamin E polyethylene glycol succinate is 1:0.05 to 1:0.

8.

3. The lutein ester flash-release tablet according to claim 1, characterized in that, The octenyl succinate-modified porous starch has a degree of substitution of 0.005 to 0.020, an average pore size of 0.5 to 30 μm, and an oil absorption value of 0.8 to 3.5 g / g.

4. The lutein ester flash-release tablet according to claim 1, characterized in that, The mass ratio of zein, tannic acid and low-ester pectin is 1:0.03-0.4:0.2-1.

5.

5. The lutein ester flash-release tablet according to claim 1, characterized in that, In the trehalose-mannitol freeze-drying protectant, the mass ratio of trehalose to mannitol is 1:0.5 to 1:

4.

6. The lutein ester flash-release tablet according to claim 1, characterized in that, The porous dry particles of lutein ester have a porosity of 35-85%, and after redispersion in water, they form droplets with a D90 of no more than 600 nm.

7. The lutein ester flash-release tablet according to claim 1, characterized in that, In the mannitol-erythritol complex sugar alcohol, the mass ratio of mannitol to erythritol is 1:0.2 to 1:

2.

8. The lutein ester flash-release tablet according to claim 1, characterized in that, The lutein ester flash-release tablets also include 0.1-3% of a flavoring agent; the flavoring agent is selected from one or more of sucralose, steviol glycosides, mogrosides, citric acid, malic acid, peppermint flavor, and blueberry flavor.

9. A method for preparing lutein ester flash-release tablets according to any one of claims 1 to 8, characterized in that, Includes the following steps: S1. Disperse porous starch in water, adjust the pH to 7.5-9.0, add octenyl succinic anhydride, react at 20-45℃ for 1-6 hours, wash and dry to obtain octenyl succinic acid esterified modified porous starch; S2. Dissolve lutein ester in an oil phase containing medium-chain triglycerides, phospholipids and vitamin E polyethylene glycol succinate to obtain an oil phase containing lutein ester. S3. Octenyl succinate-modified porous starch and low-ester pectin are dispersed in an aqueous phase, and the oil phase containing lutein ester is added. The mixture is sheared and emulsified at 8000-18000 rpm for 2-8 minutes at 20-35°C to obtain a crude emulsion. S4. Dissolve zein and tannic acid in an ethanol aqueous solution with a volume fraction of 60-85%, add the crude emulsion, adjust the pH of the system to 4.0-5.5, and then homogenize under high pressure at 40-80 MPa 2-5 times, and the material temperature during the homogenization process does not exceed 45℃ to obtain lutein ester emulsion. S5. Add trehalose, mannitol and L-leucine to the lutein ester emulsion, adjust the solid content to 10-30%, atomize it in a freezing medium of -40°C to -196°C to form frozen particles, and then freeze-dry it to obtain porous dry lutein ester particles. S6. The porous dry particles of lutein ester are mixed with mannitol-erythritol complex sugar alcohol, crospovidone, silicified microcrystalline cellulose, sodium stearate fumarate and flavoring agent, and compressed into tablets to obtain the lutein ester flash release tablets.

10. The use of the lutein ester flash-release tablets according to any one of claims 1 to 8 in the preparation of food, health food or nutritional supplement for relieving visual fatigue.

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