Solid-liquid separation product and preparation method thereof

Abstract

The invention relates to the technical field of functional food preparation, in particular to a solid-liquid separation product and a preparation method thereof. The composition comprises a tablet part and a liquid part, the tablet part contains grape seed extract, haematococcus pluvialis astaxanthin microcapsule powder and phyllanthus emblica concentrated powder, and the liquid part contains olive fruit powder, epigallocatechin gallate and aronia melanocarpa fruit powder. By means of the solid-liquid separation separated packaging design, tablets and liquid are respectively stored in a sealed mode before use. According to the design, polyphenol active ingredients can be effectively prevented from being oxidized and decomposed, the stability and bioavailability are remarkably improved, the taste is improved, tablet liquid compounding synergism is achieved, and the anti-saccharification and whitening comprehensive effect is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of functional food preparation, and particularly to a solid-liquid separation product and a preparation method thereof. Background Art

[0002] With the continuous growth of people's demand for health and appearance management, anti-glycation and whitening have become important research topics in the fields of beauty and health care. Among them, "glycation" generally refers to the non-enzymatic reaction between proteins and sugars (mainly glucose, fructose, or galactose, etc.) in the human body, thereby generating advanced glycation end products (hereinafter referred to as AGEs). AGEs can cause irreversible damage to biological macromolecules such as body proteins and lipids, and then lead to various pathological changes related to aging. The loss of skin elasticity, dull skin color, deepening of wrinkles, and loss of collagen may all be related to the excessive generation of AGEs. Therefore, how to effectively inhibit the glycation reaction, reduce the generation of AGEs, and continuously improve the overall state of the skin and body in daily diets or health products has become an important demand in the beauty and nutritional health care industries.

[0003] Similar to anti-glycation, the whitening effect also has a broad market demand in the nutritional health care and beauty cosmetics industries. Traditional whitening formulas mostly rely on ingredients such as vitamin C, arbutin, and glutathione. However, due to consumers' increasing preference for natural and healthy raw materials, the demand for using various plant extracts to achieve skin whitening and brightening has been increasing in recent years. For example, a Chinese invention patent (publication number: CN114223904A, publication date: 2022-03-25) discloses a formula for a whitening and anti-glycation health product. By weight, the formula of the present invention includes: 10-65 parts of the first component and 20-50 parts of the second component; wherein: the first component is selected from one or more of glutathione, yeast products, astaxanthin, algal products, vitamin C, grape seed extract, SOD, vitamin E, soy isoflavone, licorice flavone, licorice extract, and plant polyphenols, and the second component is selected from one or more of white kidney bean extract, L-arabinose, mulberry leaf extract, or validamycin. This patent scientifically combines the ingredients with anti-glycation and whitening effects, and can simultaneously achieve the functions of whitening, anti-glycation, and weight loss.

[0004] Although polyphenols have significant effects in anti-glycation and whitening, their chemical structures are mostly benzene rings combined with multiple hydroxyl groups (-OH), which bring the following difficulties: 1) Prone to oxidation: When polyphenols are in aqueous solution or exposed to air, the hydroxyl groups are extremely easy to be oxidized, thereby losing or weakening their activity. Especially some anthocyanin or proanthocyanin compounds are very sensitive to environmental factors such as oxygen, heat, and light, and are extremely prone to degradation or denaturation.

[0005] 2) Difficult to dissolve in water and have a poor taste: Polyphenols such as proanthocyanidins are often hydrophobic or lipophilic, and are difficult to form a stable solution with water. At the same time, these substances themselves often have unpleasant tastes such as bitterness. If they are directly dissolved in beverages or oral liquids, they are likely to cause taste discomfort to consumers.

[0006] 3) Insufficient stability: If polyphenol active substances are directly made into premixed liquids, their activity will quickly decrease and their shelf life will be greatly shortened during storage, transportation or sales due to the influence of external factors such as light, heat, oxygen and microorganisms. Many requirements for "low temperature and dark storage" cannot be guaranteed in a normal temperature sales environment.

[0007] In order to solve the above problems, the traditional approach is usually to introduce more stabilizers, preservatives or antioxidants into the formula to extend the shelf life; there are also attempts to use special processes, such as microencapsulation or liposome encapsulation technology, to protect polyphenols; in addition, the main active ingredients are directly made into solid preparations (such as capsules, tablets, powders), and the auxiliary solution is made into a solvent or diluent separately, and then blended by itself when used. However, these practices also have some shortcomings. For example: 1) Long-term use of high levels of stabilizers and preservatives may cause consumers to worry about the safety of product additives; 2) Special processes such as microencapsulation are expensive, and some processes will reduce the bioavailability of the final active ingredients; 3) Consumers are required to blend by themselves when actually using it, which is not only cumbersome, but also has high requirements for environmental hygiene and blending ratios. Improper operation will affect the efficacy.

[0008] In terms of the packaging of functional foods and health products, for example, the Chinese utility model patent applied for by the applicant (patent application number: 202423204281.0, application date, December 25, 2024) adopts the form of a "solid-liquid separation bottle" to achieve the product dosage form of upper tablets and lower liquids in order to keep the solids and liquids separated before use. The solid materials (usually powders or granules) are independently sealed in the bottle cap or additional bin, and the bottle body is loaded with liquid. When consumers use it, they rotate or press the bottle cap mechanism to make the solid part fall into the liquid for instant mixing, thereby minimizing the risk of the active ingredients being destroyed during the liquid storage process. Summary of the invention

[0009] Based on the growing demand for anti-glycation and whitening products in the current beauty and health care fields, and aiming at the drawbacks of traditional premixed liquid preparations that are difficult to balance in terms of activity, stability, and taste, the present invention provides a tablet-liquid composition for anti-glycation and whitening. The formula takes into account the synergistic effects of various ingredients such as grape seed extract, Haematococcus pluvialis astaxanthin microcapsule powder, Phyllanthus emblica concentrated powder, olive fruit powder, epigallocatechin gallate, and black chokeberry fruit powder, greatly enhancing the effects in anti-glycation, whitening, and antioxidant aspects.

[0010] To achieve the above object, the present invention adopts the following technical solutions: An anti-glycation and whitening composition in a tablet-liquid separation dosage form, the composition consisting of a solid dosage form and a liquid dosage form, The solid dosage form contains the following raw materials: grape seed extract, Haematococcus pluvialis astaxanthin microcapsule powder, and Phyllanthus emblica concentrated powder; The liquid dosage form contains the following raw materials: olive fruit powder, epigallocatechin gallate, and black chokeberry fruit powder; Wherein, the solid dosage form and the liquid dosage form are independently packaged or stored separately so that the solid dosage form and the liquid dosage form remain separated before use and are independently packaged or stored separately before use. When used, the solid dosage form and the liquid dosage form are taken simultaneously.

[0011] Preferably, the active ingredients of the solid dosage form are composed of the following components by mass fraction: 5 - 40 parts of grape seed extract; 1 - 10 parts of Haematococcus pluvialis astaxanthin microcapsule powder; 10 - 50 parts of Phyllanthus emblica concentrated powder.

[0012] Preferably, the solid dosage form is prepared by the following steps: mixing grape seed extract, Haematococcus pluvialis astaxanthin microcapsule powder, and Phyllanthus emblica concentrated powder in a predetermined ratio, adding appropriate excipients to granulate or directly pressing into tablets to obtain the solid dosage form; the outside of the solid dosage form can be optionally coated to improve the taste and further prevent the oxidation of proanthocyanidins and astaxanthin in a moisture environment.

[0013] Preferably, the solid dosage form is a tablet, and the tablet is prepared from the following components by mass percentage: 5.0% - 40.0% of the active ingredients of the solid dosage form, and the excipients include one or more of sorbitol, erythritol, mannitol, maltitol, isomaltulose, isomaltooligosaccharide, microcrystalline cellulose, maltodextrin, resistant dextrin, whole milk powder, malic acid, citric acid, magnesium stearate, food flavor, fruit juice powder, and compound film-forming agent.

[0014] Preferably, the active ingredient of the solid dosage form further comprises one or more of the following raw materials: mangosteen powder, pomegranate juice powder, rose hip powder, lophatherum gracile powder, and black pepper extract.

[0015] More preferably, the active ingredient of the solid dosage form further comprises 5-10 parts of black pepper extract.

[0016] Preferably, the active ingredient of the liquid dosage form is composed of the following components by mass: 1-4 parts of olive fruit powder; 0.1-2.0 parts of epigallocatechin gallate; 2-10 parts of black chokeberry fruit powder.

[0017] Preferably, the liquid dosage form is prepared by the following steps: mixing olive fruit powder, epigallocatechin gallate and black chokeberry fruit powder in a predetermined ratio; adding an appropriate amount of deionized water in an inert gas or low-oxygen environment and stirring well to dissolve, to obtain a stable liquid dosage form solution; filling and sealing under sterile conditions.

[0018] Preferably, the active ingredient of the liquid dosage form is 1.0%-20.0%, and the excipient is 80-99%. The excipient includes one or several of erythritol, isomaltooligosaccharide powder, xylitol, fruit juice, citric acid, malic acid, xanthan gum, pectin, sucralose, stevioside, food flavor, polydextrose, sorbitol, xylooligosaccharide, lactitol, resistant dextrin, fructooligosaccharide.

[0019] More preferably, the specific method for preparing the liquid dosage form is as follows: (1) Raw material formula: The liquid part is composed of olive fruit powder, epigallocatechin gallate and black chokeberry fruit powder. Through the synergistic effect of the extracts, it can form a complement with the solid dosage form in terms of whitening, anti-glycation and antioxidant. At the same time, the black chokeberry fruit powder brings a certain fruity aroma and sweet and sour taste; (2) Dissolution and formulation: In an inert gas or low-oxygen environment, first dissolve an appropriate amount of epigallocatechin gallate in purified water and maintain the solution temperature below 40°C to prevent the denaturation of epigallocatechin gallate; the olive fruit powder can be directly poured into the solution and stirred to dissolve; the black chokeberry fruit powder needs to be fully dissolved under warm water conditions while taking into account the sweetness and color stability of the solution; according to sensory and functional requirements, the pH value, sweetness or osmotic pressure can be appropriately adjusted to achieve a better taste and drinkability; (3) Sterilization and filling: After the mixed solution is precisely filtered, it can be filled into the bottle body by using pasteurization or aseptic filling process, and sealed in time to avoid microbial contamination and oxidation.

[0020] Preferably, when using the composition, take out the solid dosage form and use it simultaneously with the liquid dosage form through the solid dosage form. In this way, there is no need to pour extra water to take the solid dosage form, making it more convenient to take. At the same time, drink immediately after mixing the solid dosage form and the liquid dosage form to maximize the stability of active ingredients such as proanthocyanidins.

[0021] Due to the adoption of the above technical solution, the present invention has the following technical effects: 1. "Solid-liquid" compounding for synergistic effect, enhancing anti-glycation and whitening effects The present invention forms the solid dosage form of polyphenols and unsaturated fatty acids (especially proanthocyanidins, astaxanthin microcapsule powder of Haematococcus pluvialis, etc.) that are susceptible to environmental factors, and stores them separately from the liquid dosage form (olive fruit powder, epigallocatechin gallate, black chokeberry fruit powder, etc.) that is easily soluble in water and has a unique flavor and auxiliary beauty effects. When in use, take the "solid-liquid" simultaneously to form a synergistic effect: On the one hand, the polyphenol and vitamin active ingredients such as grape seed extract, astaxanthin microcapsule powder of Haematococcus pluvialis, and phyllanthus emblica concentrated powder in the solid dosage form can be rapidly released or dissolved after being mixed with the liquid dosage form, and at the same time interact with the components such as olive fruit powder, epigallocatechin gallate, and black chokeberry fruit powder in the liquid dosage form, enhancing the body's antioxidant and free radical scavenging abilities, thus more effectively inhibiting the glycation reaction.

[0022] On the other hand, the combined flavor of the solid dosage form and the liquid dosage form is better: the bitterness of the grape seed extract can be neutralized by the appropriate sweetness or fruit acid sense in the liquid dosage form, thereby improving the overall taste and promoting continuous taking. At the same time, the liquid dosage form excipients can increase the dispersion degree and dissolution degree of the solid dosage form components in the gastrointestinal tract, contribute to the absorption and utilization of the active ingredients, and finally present an excellent comprehensive effect of anti-glycation and whitening.

[0023] 2. The solid dosage form and the liquid dosage form are separated and independently protected to maintain efficacy and stability Since polyphenols are susceptible to hydrolysis, oxidation, and the influence of light and heat, if they are directly made into a premixed liquid dosage form, the degradation rate during storage will be significantly accelerated and the shelf life will be shortened. The present invention makes the relatively unstable or poor-tasting components such as grape seed extract, astaxanthin microcapsule powder of Haematococcus pluvialis, and phyllanthus emblica concentrated powder into solid dosage forms, and makes the relatively easily soluble components such as olive fruit powder, EGCG, and black chokeberry fruit powder into liquid dosage forms, and packages or stores them separately in the "dry-wet" state to form double protection: Protection of solid dosage forms: Grape seed extract, Haematococcus pluvialis astaxanthin microencapsulated powder, etc. in the form of solid dosage forms have better heat and oxygen resistance. The tablet core or outer coating can isolate the intrusion of moisture and oxygen in the environment, reducing the oxidation risk of polyphenols; under the conditions of packaging materials, storage in a dry environment, and no direct contact with water, the key active substances in the solid dosage form can maintain a high content for a long time.

[0024] Protection of liquid dosage forms: The acidity, sweetness, osmotic pressure or pH value of the liquid dosage form can be adjusted according to the formula requirements, making the active ingredients relatively stable before drinking. The liquid dosage form and the solid dosage form do not affect each other in independent packages, avoiding chemical degradation or flavor deterioration caused by premature mixing of the solid and liquid dosage forms. In addition, antioxidant measures or nitrogen filling packaging can be reasonably added to the liquid dosage form part to further improve the preservation effect.

[0025] Through the synergistic effect of the above two points, while ensuring the high-efficiency synergistic anti-glycation and whitening effects of various polyphenols and other active substances in the formula, the present invention significantly improves the stability of the product during storage and transportation; consumers only need to press a button (or rotate once) to complete the mixed administration during daily use, which can maximize the freshness and concentration of the active ingredients, and can also obtain a more acceptable taste and better administration experience. In summary, the present invention realizes the technical effects of "solid-liquid" compounding and synergistic enhancement and separate independent protection, greatly improving the overall quality and economic value of functional foods and health products. Brief Description of the Drawings

[0026] Figure 1 It is a micrograph of the melanin in the head of zebrafish after sample treatment. Detailed Description of the Invention

[0027] The following combines the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0028] The raw material sources of the embodiments of the present application are as follows:

[0029] Other components are conventional auxiliary materials purchased from the market.

[0030] Example 1: Tablet + Liquid Dosage Form Combination 1.1 Core Tablet Core Formula (about 400 mg per tablet for 100 tablets)

[0031] 1.2 Film coating layer (coating weight gain is about 2%)

[0032] Actual coating amount: Based on the weight of the tablet core of 400 mg × 2% = 8 mg / tablet.

[0033] 1.3 Preparation process 1) Sieving: All dry materials are sieved through 80 - 100 meshes to ensure uniform fineness; for dry mixing, a three-dimensional mixer is used: First, pre-mix the active ingredient + resistant dextrin + milk powder at low speed for 5 minutes; Second, add sorbitol + maltitol + microcrystalline cellulose for 5 minutes; Then, add malic acid + essence + magnesium stearate for 2 minutes.

[0034] 2) Direct compression: The mold is Ø8 mm and the tablet thickness is about 4 mm; the pressure is 10 - 15 kN, the hardness is ≥70 N, and the disintegration time is ≤4 minutes.

[0035] 3) Coating: Dissolve the coating powder (A - D) in pure water (solid content 10%); perform fluidized bed coating with an inlet air temperature of 40°C and a coating weight gain of 2%.

[0036] 1.4 Liquid dosage form formula (100 mL, w / w%)

[0037] 1.5 Liquid preparation method: In a low-oxygen inert environment, pre-dissolve epigallocatechin gallate; sequentially add olive fruit powder and aronia melanocarpa fruit powder to water at 30 - 35°C; add other excipients and stir evenly; after high-speed homogenization for 10 minutes, slowly add pectin; deoxygenate under vacuum, fill, seal, and store at room temperature in the dark.

[0038] The prepared powder and liquid dosage forms are separately packaged in the liquid storage bottle described in the Chinese utility model patent applied by the applicant (Patent Application No.: 202423204281.0, Application Date: December 25, 2024).

[0039] Example 2: Tablet + liquid dosage form combination 2.1 Core tablet core formula (100 tablets, about 400 mg per tablet)

[0040] The film coating layer, preparation process, and liquid dosage form refer to Example 1.

[0041] Example 3: Tablet + liquid dosage form combination 3.1 Core tablet core formula (100 tablets, about 400 mg per tablet)

[0042] The film coating layer, preparation process, and liquid dosage form refer to Example 1.

[0043] Comparative Example 1 Using the same formula as the liquid in Example 1, but without preparing tablets. Grape seed extract, Haematococcus pluvialis astaxanthin microencapsulated powder, and Phyllanthus emblica concentrated powder were all premixed in the liquid to form a single liquid dosage form product.

[0044] Comparative Example 2 Only using the same tablet formula as in Example 1, but without preparing the liquid. Olive fruit powder, epigallocatechin gallate, and black chokeberry fruit powder were added to the tablet formula to prepare a single tablet product.

[0045] Experimental Example 1 Anti-glycation and Whitening Synergistic Effect in Zebrafish Model I. Experimental Purpose By establishing an anti-glycation and whitening synergistic model in zebrafish, evaluate the effects of grape seed extract, Haematococcus pluvialis astaxanthin microencapsulated powder, Phyllanthus emblica concentrated powder (solid dosage form components) and olive fruit powder, EGCG, black chokeberry fruit powder (liquid dosage form components) taken alone or simultaneously on the generation of advanced glycation end products (AGES), antioxidant capacity, and skin whitening effect, and prove that the above combination has an obvious synergistic effect when taken simultaneously.

[0046] II. Materials and Instruments

[0047] III. Reagent Preparation 1. Induction solution: 0.25 mM D-galactose, 0.05 mM MG-BSA; diluted with sterilized E3 and prepared freshly before use.

[0048] 2. S-Mix Working Solution High dose: 40 µg : (Total active powder) Medium dose: 20 µg Low dose: 10 µg 3. L-Mix Working Solution High dose: 90 µg (Total active powder) Medium dose: 45 µg Low dose: 22.5 µg 4. Compound group (S+L): Mix immediately at 1:1 (w / w).

[0049] 5. Positive control: 200 µM arbutin dissolved in E3.

[0050] The above reagents are filtered through 0.22 µm, and all solutions are stored in the dark at 4 °C for ≤24 h.

[0051] IV. Experimental grouping (n = 30 tails / group, three wells in parallel)

[0052] The concentration refers to the total active powder, and all contain the inducer.

[0053] IV. Operation procedure 4.1 Embryo preparation Adult fish are mated and isolated in the evening; fertilized embryos are collected the next morning, and abnormal embryos are removed under a microscope. Healthy embryos are placed in E3 at 28 °C until 6 hpf for the experiment.

[0054] 4.2 Prescreening of the maximum tolerated concentration (MTC) Take 5 tails / well, and observe the malformation rate at gradients of 7.8–62.5 µg·mL⁻¹ for 48 h to determine the subsequent highest dosing concentration.

[0055] 4.3 Formal exposure Replace the liquid: Remove E3 and add 3 mL of the solution containing the inducer & treatment solution (or control solution).

[0056] Cultivation conditions: 28 °C, 14 h light / 10 h dark cycle; change the liquid once a day to keep the concentration constant.

[0057] Treatment duration: 48 h continuous exposure.

[0058] 4.4 Index detection

[0059] 4.5 Image analysis Software: Image-J; Set a unified threshold and measure the RGB grayscale or fluorescence integral.

[0060] Result representation: mean±SEM.

[0061] 4.6 Statistics One-way ANOVA + Tukey’s; P < 0.05 is significant, P < 0.01 is extremely significant.

[0062] V. Anti-glycation and whitening compound synergistic test on zebrafish - measured data (n = 30, mean±SEM)

[0063] Inhibition rate / Whitening rate = (Value of the model group - Value of the treatment group) ÷ Value of the model group × 100%. † The results of T-AOC are expressed as the percentage increase compared to the model group.

[0064] VI. Statistical Significance For S-Mix, L-Mix, de-EGCG, and de-grape seed extract, p < 0.05 compared with the model group.

[0065] For the S+L combination, p < 0.01 compared with any single component or absence of a component (One-way ANOVA and Tukey).

[0066] VII. Result Interpretation 1. Single component is effective: Both S-Mix and L-Mix can reduce AGEs (35–40%) and melanin (≈28%).

[0067] 2. Synergistic effect of compounding: When S+L are used simultaneously, the AGE inhibition rate increases to 68% and the whitening rate reaches 64%, with an increase amplitude ≥25%, showing a > additive effect.

[0068] 3. Key synergistic factors: After removing EGCG or grape seed extract, the effect is between that of a single component and full compounding, confirming that the two are the core of synergy.

[0069] 4. Comparison with positive control: The results of S+L are equivalent to or slightly better than those of 200 µM arbutin, verifying the reliability of the model and the clinical-grade potential of the composition.

[0070] Zebrafish data demonstrate that when the solid dosage forms (grape seed extract, Haematococcus pluvialis astaxanthin microcapsule powder, Phyllanthus emblica concentrated powder) and liquid dosage forms (olive fruit powder, EGCG, black chokeberry fruit powder) in the present invention are taken simultaneously, significant synergistic anti-glycation and whitening enhancement effects can be produced, far exceeding that of any single component or absence of a component.

[0071] Experimental Example 2 Bioavailability in Zebrafish - Scale-up Verification Experiment I. Objective Within the anti-glycation - whitening model framework established in Experimental Example 1, quantitatively compare the in vivo exposure of polyphenol core components (OPC and EGCG) with / without black pepper extract; further correlate the pharmacokinetic increase amplitude with the changes in functional endpoints (AGEs-ROS-melanin) to confirm that black pepper extract has the effect of promoting absorption and improving bioavailability.

[0072] II. Key Principle 1. Black pepper extract inhibits intestinal P-gp efflux and UGT-mediated glucuronidation; 2. The intestinal-liver system of zebrafish is complete at 5–8 dpf, and real in vivo pharmacokinetics can be detected.

[0073] III. Experimental Design

[0074] Plasma: After anesthesia by ice bath, the tail was cut, blood was collected with a capillary tube, and 6 tails were combined into 1 sample; 3 batches in parallel.

[0075] IV. Core Detection Methods

[0076] V. Representative Results (mean±SEM, n = 3 batches) 5.1 Pharmacokinetics

[0077] The increasing trend of Cmax was consistent (see the attached figure), and Tmax remained unchanged at 0.5 h.

[0078] 5.2 P-gp Efflux

[0079] 5.3 Functional Association (8 dpf Endpoint)

[0080] Statistics: P < 0.01 when comparing the black pepper extract group with the BL-Mix (ANOVA + Tukey). The reduction in AGE / ROS / melanin was significantly negatively correlated with the increase in AUC (r = -0.93, P < 0.005).

[0081] VI. Conclusion 1. After adding black pepper extract, the AUC of OPC and EGCG in vivo increased significantly in the range of 1.7 - 2.1 times; 2. Black pepper extract simultaneously inhibited the intestinal P-gp efflux in zebrafish by 40 - 45%, explaining the mechanism of the increase in blood drug concentration; 3. The increase in pharmacokinetics was directly reflected in the functional endpoint - the generation of AGE, the level of ROS, and melanin deposition all decreased by another 10 - 16 percentage points; 4. 0.3 mM black pepper extract showed no malformation or death, with a sufficient safety window.

[0082] The experiment clearly demonstrated that black pepper extract can significantly promote the absorption of polyphenolic active ingredients, improve bioavailability, and ultimately amplify the comprehensive anti-glycation and whitening effects.

[0083] Test Example 3 Stability Test of Tablet + Liquid Dosage Form Combination I. Test Objectives Through this stability test, the significant advantages of the separate independent packaging of solid dosage forms and liquid dosage forms (Examples 1 to 3) compared to the single dosage form prepared by premixing solid dosage forms and liquid dosage forms (Comparative Example 1 and Comparative Example 2) in terms of the stability of the active ingredient and antioxidant capacity are verified, thereby proving that the packaging method of the present invention can effectively protect the active ingredient and maintain the efficacy.

[0084] II. Test Method 1. Preparation of experimental samples Prepare samples according to Examples 1 to 3 and Comparative Examples 1-2 respectively.

[0085] 2. Storage conditions and periods Store the above experimental samples under two conditions: normal temperature (25°C ± 2°C, humidity 60 ± 5%RH); accelerated (40°C ± 2°C, humidity 75 ± 5%RH); samples are taken for testing after storage for 0, 3, and 6 months respectively.

[0086] 3. Detection indexes and methods Detection of procyanidin content (HPLC method); detection of EGCG content (HPLC method); detection of antioxidant capacity (DPPH free radical scavenging rate); sensory and appearance evaluation (color, clarity, taste).

[0087] III. Experimental data 1. Retention rate of OPC and EGCG content (%) 1.1 Normal temperature 25°C

[0088] 1.2 Accelerated 40°C

[0089] 2. Antioxidant capacity (DPPH scavenging rate %)

[0090] 3. Sensory / appearance score (on a 10-point scale)

[0091] IV. Statistics and conclusions 1. In Examples 1-3, OPC ≥ 90% and EGCG ≥ 89% were still maintained at normal temperature for 6 months, the attenuation of DPPH activity was ≤ 10%, and the appearance score was ≥ 9 points; 2. For Comparative Example 1 (completely liquid) and Comparative Example 2 (completely solid), the remaining rates of EGCG / OPC dropped to 15% and 39% respectively, the antioxidant capacity remained only 20 - 35%, and the sensory properties deteriorated significantly (P < 0.01).

[0092] 3. The gap is further amplified under accelerated conditions: the overall content in the examples is still > 75%, while in Comparative Example 1, there is only 5% EGCG and 12% OPC left.

[0093] Conclusion: Using the separated independent packaging of the present invention can significantly inhibit polyphenol oxidation and degradation, maintain antioxidant activity and product sensory properties; while rapid inactivation and browning occur when mixed into a single dosage form. The significant advantages of the packaging solution of the present invention in terms of stability and efficacy retention.

[0094] The above is the description of the embodiments of the present invention. Through the above description of the disclosed embodiments, those skilled in the art can implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art. The general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but will conform to the widest scope consistent with the principles and novel points disclosed herein.

Claims

1. An anti-glycation and whitening composition in the form of a film-liquid separation type, characterized in that, The composition consists of a solid dosage form and a liquid. The active ingredients of the solid dosage form include the following raw materials: grape seed extract, Haematococcus pluvialis astaxanthin microencapsulated powder, and Phyllanthus emblica concentrated powder. The active ingredients of the liquid dosage form include the following raw materials: olive fruit powder, epigallocatechin gallate, and Aronia melanocarpa fruit powder. Among them, the solid dosage form and the liquid dosage form are independently packaged or stored separately so that the solid dosage form and the liquid dosage form remain separated before use and are independently packaged or stored separately before use. When in use, the solid dosage form and the liquid dosage form are taken simultaneously.

2. The composition according to claim 1, characterized in that, The active ingredients of the solid dosage form are composed of the following components by mass fraction: Grape seed extract 5 - 40 parts; Haematococcus pluvialis astaxanthin microencapsulated powder 1 - 10 parts; Phyllanthus emblica concentrated powder 10 - 50 parts.

3. The composition according to claim 2, characterized in that, The solid dosage form is prepared by the following steps: mixing grape seed extract, Haematococcus pluvialis astaxanthin microencapsulated powder, and Phyllanthus emblica concentrated powder in a predetermined ratio, adding appropriate excipients to make powder, granulate, or compress into tablets to obtain the solid dosage form; optionally coating the outside of the solid dosage form to improve the taste and further prevent the oxidation of proanthocyanidins in a moisture environment.

4. The composition according to claim 3, characterized in that, The solid dosage form is a tablet, and the active ingredients of the solid dosage form are 5.0% - 40.0%. The excipients include one or more of sorbitol, erythritol, mannitol, maltitol, isomaltulose, isomaltooligosaccharide, microcrystalline cellulose, maltodextrin, resistant dextrin, whole milk powder, malic acid, citric acid, magnesium stearate, food flavor, fruit juice powder, and compound film-forming agent.

5. The composition according to any one of claims 1-4, characterized in that The active ingredients of the solid dosage form further include one or more of the following raw materials: mangosteen powder, pomegranate juice powder, Rosa roxburghii powder, lophatherum gracile powder, and black pepper extract.

6. The composition according to claim 5, wherein The active ingredients of the solid dosage form further include 5 - 10 parts of black pepper extract.

7. The composition according to claim 1, wherein The active ingredients of the liquid dosage form are composed of the following components by mass fraction: Olive fruit powder 1 - 4 parts; Epigallocatechin gallate 0.1 - 2.0 parts; Aronia melanocarpa fruit powder 2 - 10 parts.

8. The composition according to claim 7, wherein The liquid dosage form is prepared by the following steps: mixing olive fruit powder, epigallocatechin gallate, and Aronia melanocarpa fruit powder in a predetermined ratio; adding appropriate deionized water in an inert gas or low-oxygen environment and stirring well to dissolve to obtain a stable liquid dosage form solution; filling and sealing under sterile conditions.

9. The composition according to claim 7 or 8, characterized in that, The active ingredients of the liquid dosage form are 1.0% - 20.0%, and the excipients are 80 - 99%. The excipients include one or more of erythritol, isomaltooligosaccharide powder, xylitol, fruit juice, citric acid, malic acid, xanthan gum, pectin, sucralose, stevioside, food flavor, polydextrose, sorbitol, xylo-oligosaccharide, lactitol, resistant dextrin, and fructo-oligosaccharide.

10. A method for preparing the composition according to any one of claims 1-9, characterized in that, Including the following steps: (1) Mix grape seed extract, Haematococcus pluvialis astaxanthin microencapsulated powder, and Phyllanthus emblica concentrated powder and add excipients to make a solid dosage form. (2) Dissolve olive fruit powder, epigallocatechin gallate, and Aronia melanocarpa fruit powder in water to make a liquid dosage form. (3) Independently package or separately store the solid dosage form and the liquid dosage form respectively, so that the solid dosage form and the liquid dosage form remain separated before use.

Images