Wrinkle-removing, freckle-removing and anti-aging composition and preparation method thereof

Abstract

The invention belongs to the technical field of medicines, and relates to a wrinkle-removing, freckle-removing and anti-aging composition, in particular to an enteric microcapsule which comprises a capsule core oil phase and a capsule skin covering the surface of the capsule core oil phase, and the capsule core oil phase comprises ellagic acid and rhus chinensis fruit oil; the capsule skin is prepared from arabinoxylan, hydroxypropyl methyl cellulose, sodium alginate, lactitol and polyethylene glycol. The anti-wrinkle, anti-freckle and anti-aging composition has the advantages that the ellagic acid is small in side effect and high in bioavailability, the ellagic acid and the rhus chinensis fruit oil have a synergistic effect, and the anti-wrinkle, anti-freckle and anti-aging effects are good.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and in particular relates to a wrinkle-removing, freckle-removing and anti-aging composition and a preparation method thereof. Background Art

[0002] Skin is susceptible to aging due to factors such as age, environment, genetics, diet, and sun exposure. If skin is chronically oxidized, poorly cared for, or if the body's APSCs (multipotent cells) decline with aging, dead skin cells will cling to the surface and not fall off, causing a series of problems and seriously affecting beauty. This is the aging process.

[0003] Wrinkles are a primary sign of skin aging. Most facial wrinkles are caused by the frequent movement of facial muscles, which causes repeated stretching and puckering of the skin. However, some fine wrinkles are caused by the aging of the skin over time, which leads to the breakage of elastic fibers and loss of collagen in the superficial dermis. This leads to a loss of the network of elastic fibers and collagen in the superficial dermis, resulting in fine wrinkles. Skin aging can also cause abnormalities in melanocyte metabolism, leading to the accumulation of dark spots in the epidermis.

[0004] Ellagic acid is a natural phenolic antioxidant found in numerous fruits and vegetables, including blackberries, raspberries, strawberries, cranberries, pecans, pomegranates, and goji berries. Ellagic acid exhibits a wide range of pharmacological activities, and its potential health benefits, including anti-inflammatory, antioxidant, anti-tumor, cardiovascular, organ-protective, blood sugar regulation, and antibacterial properties, are attracting increasing attention. Its antioxidant activity has been used for wrinkle and freckle removal, as well as for anti-aging.

[0005] Ellagic acid is a natural antioxidant that effectively scavenges free radicals in the body, such as oxygen and hydroxyl radicals. Free radicals are a major factor in causing oxidative damage to cells and accelerating aging. Ellagic acid scavenges free radicals and reduces their attack on cells, thereby protecting cell structure and function and delaying cellular aging. Ellagic acid can also inhibit lipid peroxidation induced by ampicillin and lipid peroxidation caused by exogenous substances in tissues. Lipid peroxidation can damage cell membranes and affect the normal function of cells. By inhibiting lipid peroxidation, ellagic acid protects the integrity of cell membranes and maintains the normal physiological activities of cells. Ellagic acid can promote collagen synthesis, enhance skin elasticity, reduce the formation of wrinkles, and keep the skin youthful. Ellagic acid can inhibit the activity of tyrosinase and reduce the production of melanin, thereby helping to lighten spots, brighten the skin tone, make the skin more fair, improve the skin's appearance, and delay skin aging.

[0006] The solubility of ellagic acid in water is only 9.81 μg / mL, resulting in extremely low dissolution rate and dissolution rate. Its lipid solubility is also poor, making it difficult to transport across membranes into the bloodstream and resulting in low bioavailability. Ellagic acid is digested and absorbed primarily in the intestine. A small amount of ellagic acid is directly absorbed into the bloodstream by intestinal epithelial cells. Under the action of intestinal probiotics, the majority of ellagic acid is converted into highly bioavailable urolithins through lactone ring cleavage, decarboxylation, and dehydroxylation reactions. As its lipophilicity increases, it is transported through intestinal epithelial cells into the bloodstream. If taken directly orally, ellagic acid combines with pepsin under acidic conditions (pH 1-2) to form an indigestible complex that remains in the stomach, impairing digestion and causing symptoms such as abdominal distension and pain. It may also form gastric stones. The astringent properties of ellagic acid can also lead to excessive water absorption in the gastrointestinal tract, slowing gastrointestinal motility and causing side effects such as constipation, nausea, and dizziness.

[0007] There is an urgent need to develop an oral preparation of ellagic acid with fewer side effects and high bioavailability. Summary of the Invention

[0008] The present invention provides a wrinkle-removing, freckle-removing and anti-aging composition with small side effects and high bioavailability, and a preparation method thereof.

[0009] A wrinkle-removing, freckle-removing and anti-aging composition comprises a capsule core oil phase and a capsule skin coated on the surface of the capsule core oil phase, wherein the capsule core oil phase comprises 0.3-0.5 parts by weight of ellagic acid and 2.4-2.8 parts by weight of rhus chinensis oil; and the capsule skin comprises 4.0-8.0 parts by weight of arabinoxylan, 0.1-0.3 parts by weight of hydroxypropyl methylcellulose, 2.0-3.0 parts by weight of sodium alginate, 1.0-1.6 parts by weight of lactitol and 0.7-1.0 parts by weight of polyethylene glycol.

[0010] The ellagic acid is derived from raspberries, gallnuts, blackberries or pomegranate peels.

[0011] The present invention prepares ellagic acid into enteric-coated microcapsules to avoid ellagic acid from irritating the gastrointestinal tract and producing side effects. In the low pH environment of the stomach, the capsule skin of the enteric-coated microcapsules swells to form a gel. In the high pH environment of the intestine, the gel decomposes into oligosaccharides or polysaccharides, and the capsule core oil phase is slowly released. The capsule skin and Rhus chinensis oil improve the activity of intestinal flora, increase the rate of conversion of ellagic acid to urolithin, and improve the bioavailability of ellagic acid.

[0012] Rhus chinensis fruit oil is a yellow, transparent, oily liquid made from Rhus chinensis fruit through processes such as gas explosion, squeezing, extraction, and filtration. Rhus chinensis fruit oil contains a variety of unsaturated fatty acids, phytosterols, vitamin E, and polyphenolic phytochemicals. Rhus chinensis fruit oil not only improves the metabolic efficiency of intestinal probiotics and promotes the conversion of ellagic acid to urolithin substances, but the unsaturated fatty acids in it also enhance the absorption efficiency of urolithin substances, increasing the bioavailability of ellagic acid. The abundant polyphenols in Rhus chinensis fruit oil can also inhibit the activity of tyrosinase, reduce the production of melanin, and have a good whitening and freckle-removing effect. The phytosterols in Rhus chinensis fruit oil can prevent collagen decomposition, stimulate collagen production, promote the restoration of skin elasticity and structure, and reduce and prevent skin aging and wrinkles caused by ultraviolet radiation. Ellagic acid and Rhus chinensis fruit oil work together to produce a synergistic effect.

[0013] The capsule coating is composed of a mixture of sodium alginate and arabinoxylan, forming a dense, three-dimensional mesh structure. This significantly reduces the pore size of the microcapsule surface, effectively blocking gastric acid penetration, improving the mechanical properties of the microcapsules, and slowing the release rate of ellagic acid. This provides a stable blood concentration and avoids gastrointestinal irritation and side effects (hypertension, dizziness, and nausea) caused by sudden increases in ellagic acid concentration. The capsule coating also has a sustained-release effect, extending the release time of ellagic acid in the digestive tract, improving its absorption efficiency, and increasing its bioavailability.

[0014] Arabinoxylan can be broken down into arabinoxylan oligosaccharides by intestinal microorganisms. As a prebiotic, arabinoxylan oligosaccharides have the effect of increasing the metabolic activity of intestinal flora. Hydroxypropyl methylcellulose can make the particle size distribution of the oil phase in the emulsion uniform during the microcapsule preparation process, and the obtained microcapsules have a uniform particle size. As a component of the capsule shell, hydroxypropyl methylcellulose can fill and embed the gaps in the arabinoxylan, prevent and control gastric acid penetration, and protect the capsule core oil phase from the effects of gastric acid. Lactitol can regulate the intestinal flora microecology and has a good protective effect on the balance of the intestinal microecological system. It can directly or indirectly regulate the composition of beneficial and harmful bacteria in the intestine, selectively inhibit intestinal pathogens, promote the growth of beneficial bacteria, optimize the intestinal flora structure, increase the metabolic activity of the intestinal flora, and promote the conversion of ellagic acid to urolithin substances. Lactitol can also promote intestinal peristalsis, avoiding side effects such as constipation caused by the astringent effect of ellagic acid.

[0015] The capsule shell further comprises 1.3-2.0 parts by weight of oligosaccharides.

[0016] Adding a small amount of low-molecule oligosaccharides to the capsule skin reduces the particle size of the microcapsules and improves the mechanical properties of the capsule skin. As prebiotics, oligosaccharides also promote the growth of beneficial bacteria, inhibit the reproduction of harmful bacteria, improve gastrointestinal function, and prevent and alleviate symptoms such as diarrhea, bloating, and indigestion caused by ellagic acid. By regulating the metabolism of intestinal flora, the bioavailability of ellagic acid is increased.

[0017] The oligosaccharide is one or more of fructooligosaccharide, xylooligosaccharide, isomaltooligosaccharide, soybean oligosaccharide and chitosan oligosaccharide.

[0018] The capsule core oil phase includes 0.4 weight parts of ellagic acid and 2.6 weight parts of Rhus chinensis oil; the capsule skin includes 7 weight parts of arabinoxylan, 2.5 weight parts of sodium alginate, 1.5 weight parts of soybean oligosaccharides, 0.2 weight parts of hydroxypropyl methylcellulose, 1.5 weight parts of lactitol and 0.8 weight parts of polyethylene glycol.

[0019] A method for preparing the wrinkle-removing, freckle-removing and anti-aging composition comprises the following steps: (S1) passing a formulated amount of ellagic acid through a 200-250 mesh sieve, ultrasonically suspending the mixture in Rhus chinensis oil to obtain a capsule core oil phase; (S2) adding a formulated amount of arabinoxylan, sodium alginate, hydroxypropyl methylcellulose, oligosaccharides, lactitol and polyethylene glycol to 60-120 parts by weight of water, mixing the mixture evenly to obtain an aqueous phase; (S3) adding the oil phase to the aqueous phase and homogenizing the mixture to obtain an emulsion; and (S4) spray-freeze-drying the emulsion to obtain the wrinkle-removing, freckle-removing and anti-aging composition.

[0020] Among them, in (S3), emulsification and homogenization are carried out at 25°C, 25 MPa, and a flow rate of 6 L / h.

[0021] The spray freeze drying conditions in (S4) were as follows: feeding rate of 2 mL / min, inlet temperature of 180 °C, outlet temperature of 90 °C, nozzle atomization pressure of 0.4 MPa, and fan power of 10 m 3 / min, and then freeze-dried to make the finished product.

[0022] An oral pharmaceutical preparation comprises the wrinkle-removing, freckle-removing and anti-aging composition and pharmaceutically acceptable oral preparation excipients. The dosage form of the drug is granules, tablets, capsules, powders, pills, emulsions or suspensions.

[0023] Optionally, the oral preparation excipients are selected from one or more of β-cyclodextrin, magnesium stearate, hydroxypropyl cellulose, sodium hydroxymethyl starch, fructose, microcrystalline cellulose, dextrin, starch, calcium phosphate, povidone, and sodium hydroxymethyl cellulose.

[0024] The invention discloses an application of the wrinkle-removing, freckle-removing and anti-aging composition in the preparation of health-care food for wrinkle-removing, freckle-removing and anti-aging.

[0025] The wrinkle-removing, freckle-removing and anti-aging composition of the present invention adopts an enteric-coated microcapsule dosage form, which avoids ellagic acid from combining with proteins to form indigestible complexes under low pH conditions, thereby avoiding side effects such as abdominal distension and abdominal pain caused by ellagic acid; the antioxidant components in Rhus chinensis oil improve the conversion rate of ellagic acid to absorbable urolithin substances by regulating the metabolic capacity of intestinal flora; the unsaturated fatty acids in Rhus chinensis oil improve the efficiency of urolithin substances entering the blood circulation through intestinal epithelial cells, thereby improving the bioavailability of ellagic acid. Ellagic acid and Rhus chinensis oil in the wrinkle-removing and anti-aging enteric-coated microcapsules of the present invention act synergistically to inhibit tyrosinase activity, block melanin production, have freckle-removing and whitening effects, effectively promote the regeneration of skin elastic fibers and collagen, prevent elastin and collagen degradation, and especially can reduce skin tissue damage caused by long-term or frequent radiation and ultraviolet irradiation in sunlight, slow down photoaging, and have good wrinkle-removing, freckle-removing and anti-aging effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is a line graph of the in vitro dissolution rate of the anti-wrinkle, anti-freckle and anti-aging composition of Experimental Example 2 of the present invention in artificial gastric juice.

[0027] Figure 2 This is a line graph of the in vitro dissolution rate of the anti-wrinkle, anti-freckle and anti-aging composition of Experimental Example 2 of the present invention in artificial intestinal fluid.

[0028] Figure 3 This is a bar graph of the skin water content, hydroxyproline content, SOD activity and malondialdehyde content of mice in different groups in the animal experiment of Experimental Example 3 of the present invention on the anti-wrinkle, anti-freckle and anti-aging composition.

[0029] Figure 4 This is a bar graph showing the percentage reduction in chloasma score in a clinical experiment on the freckle removal function of the wrinkle-removing, freckle-removing and anti-aging composition according to Experimental Example 4 of the present invention. DETAILED DESCRIPTION

[0030] Example 1

[0031] (S1) 0.4 kg of ellagic acid was passed through a 200-mesh sieve, added to 2.4 kg of Rhus chinensis fruit oil, and ultrasonically suspended, and mixed evenly to obtain a capsule core oil phase; (S2) 8.0 kg of arabinoxylan, 0.1 kg of hydroxypropyl methylcellulose, 2.0 g of sodium alginate, 1.0 kg of lactitol, and 0.7 kg of polyethylene glycol were added to 60 L of water, mixed evenly, and obtained an aqueous phase; (S3) the oil phase was added to the aqueous phase, and emulsified and homogenized at 25 ° C, 25 MPa, and a flow rate of 6 L / h to obtain an emulsion; (S4) the emulsion was spray-freeze-dried to obtain an anti-wrinkle, anti-freckle, and anti-aging composition, and the spray-drying conditions were a feeding rate of 2 mL / min, an inlet temperature of 180 ° C, an outlet temperature of 90 ° C, a nozzle atomization pressure of 0.4 MPa, and a fan power of 10 m 3 / min, and then freeze-dried to make the finished product.

[0032] The wrinkle-removing, freckle-removing and anti-aging composition is light yellow, spherical, with a particle size of 70-140 meshes, uniform particles, no adhesion, caking or moisture, and good fluidity. Example 2

[0033] (S1) 0.4 kg of ellagic acid was passed through a 250-mesh sieve, added to 2.6 kg of Rhus chinensis fruit oil, and ultrasonically suspended, and mixed evenly to obtain a capsule core oil phase; (S2) 6.0 kg of arabinoxylan, 2.4 kg of sodium alginate, 0.3 kg of hydroxypropyl methylcellulose, 1.2 kg of lactitol, and 0.8 kg of polyethylene glycol were added to 70 L of water, mixed evenly, and obtained an aqueous phase; (S3) the oil phase was added to the aqueous phase, and emulsified and homogenized at 25 ° C, 25 MPa, and a flow rate of 6 L / h to obtain an emulsion; (S4) the emulsion was spray-freeze-dried to obtain an anti-wrinkle, anti-freckle, and anti-aging composition, and the spray-drying conditions were a feeding rate of 2 mL / min, an inlet temperature of 180 ° C, an outlet temperature of 90 ° C, a nozzle atomization pressure of 0.4 MPa, and a fan power of 10 m 3 / min, and then freeze-dried to make the finished product.

[0034] The wrinkle-removing, freckle-removing and anti-aging composition is light yellow, spherical, with a particle size of 70-140 meshes, uniform particles, no adhesion, caking or moisture, and good fluidity. Example 3

[0035] (1) 0.5 kg of ellagic acid was passed through a 250-mesh sieve, added to 2.6 kg of Rhus chinensis fruit oil, and suspended by ultrasonication. The mixture was evenly mixed to obtain the capsule core oil phase; (2) Add 7.0 kg of arabinoxylan, 2.5 kg of sodium alginate, 0.2 kg of hydroxypropyl methylcellulose, 1.5 kg of soybean oligosaccharides, 1.5 kg of lactitol, and 0.8 kg of polyethylene glycol to 90 L of water and mix well to obtain an aqueous phase; (3) The oil phase was added to the water phase and emulsified and homogenized at 25°C, 25 MPa, and a flow rate of 6 L / h to obtain an emulsion; (4) The emulsion was spray-freeze-dried to obtain a wrinkle-removing, freckle-removing and anti-aging composition. The spray-drying conditions were as follows: a feed rate of 2 mL / min, an inlet temperature of 180°C, an outlet temperature of 90°C, a nozzle atomization pressure of 0.4 MPa, and a fan power of 10 m 3 / min, and then freeze-dried to make the finished product.

[0036] The wrinkle-removing, freckle-removing and anti-aging composition is light yellow, spherical, with a particle size of 70-140 meshes, uniform particles, no adhesion, caking or moisture, and good fluidity. Example 4

[0037] (S1) 0.4 kg of ellagic acid was passed through a 200-mesh sieve, added to 2.8 kg of Rhus chinensis fruit oil, and ultrasonically suspended, and mixed evenly to obtain a capsule core oil phase; (S2) 8.0 kg of arabinoxylan, 3.0 kg of sodium alginate, 0.2 kg of hydroxypropyl methylcellulose, 0.8 kg of oligoxylose, 0.5 kg of oligochitosan, 1.5 kg of lactitol, and 1.0 kg of polyethylene glycol were added to 120 L of water and mixed evenly to obtain an aqueous phase; (S3) the oil phase was added to the aqueous phase and emulsified and homogenized at 25 ° C, 25 MPa, and a flow rate of 6 L / h to obtain an emulsion; (S4) the emulsion was spray-freeze-dried to obtain an anti-wrinkle, anti-freckle, and anti-aging composition. The spray-drying conditions were a feeding rate of 2 mL / min, an inlet temperature of 180 ° C, an outlet temperature of 90 ° C, a nozzle atomization pressure of 0.4 MPa, and a fan power of 10 m 3 / min, and then freeze-dried to make the finished product.

[0038] The wrinkle-removing, freckle-removing and anti-aging composition is light yellow, spherical, with a particle size of 70-140 meshes, uniform particles, no adhesion, caking or moisture, and good fluidity. Example 5

[0039] (S1) 0.4 kg of ellagic acid was passed through a 250-mesh sieve, added to 2.6 kg of Rhus chinensis fruit oil, and ultrasonically suspended, and mixed evenly to obtain a capsule core oil phase; (S2) 4.0 kg of arabinoxylan, 3.0 kg of sodium alginate, 0.3 kg of hydroxypropyl methylcellulose, 0.8 kg of oligoxylose, 0.5 kg of oligochitosan, 0.5 kg of oligoisomaltose, 1.6 kg of lactitol and 0.8 kg of polyethylene glycol were added to 80 L of water and mixed evenly to obtain an aqueous phase; (S3) the oil phase was added to the aqueous phase and emulsified and homogenized at 25 ° C, 25 MPa and a flow rate of 6 L / h to obtain an emulsion; (S4) the emulsion was spray-freeze-dried to obtain an anti-wrinkle, anti-freckle and anti-aging composition. The spray drying conditions were a feeding rate of 2 mL / min, an inlet temperature of 180 ° C, an outlet temperature of 90 ° C, a nozzle atomization pressure of 0.4 MPa, and a fan power of 10 m 3 / min, and then freeze-dried to make the finished product.

[0040] The wrinkle-removing, freckle-removing and anti-aging composition is light yellow, spherical, with a particle size of 70-140 meshes, uniform particles, no adhesion, caking or moisture, and good fluidity. Example 6

[0041] (S1) 0.4 kg of ellagic acid was passed through a 250-mesh sieve, added to 2.8 kg of Rhus chinensis fruit oil and ultrasonically suspended, and mixed evenly to obtain a capsule core oil phase; (S2) 6.0 kg of arabinoxylan, 2.5 kg of sodium alginate, 0.1 kg of hydroxypropyl methylcellulose, 0.8 kg of oligoxylose, 0.8 kg of oligochitosan, 0.4 kg of oligofructose, 1.6 kg of lactitol and 0.9 kg of polyethylene glycol were added to 90 L of water and mixed evenly to obtain an aqueous phase; (S3) the oil phase was added to the aqueous phase and emulsified and homogenized at 25 ° C, 25 MPa and a flow rate of 6 L / h to obtain an emulsion; (S4) the emulsion was spray-freeze-dried to obtain an anti-wrinkle, anti-freckle and anti-aging composition, and the spray drying conditions were a feeding rate of 2 mL / min, an inlet temperature of 180 ° C, an outlet temperature of 90 ° C, a nozzle atomization pressure of 0.4 MPa, and a fan power of 10 m 3 / min, and then freeze-dried to make the finished product.

[0042] The wrinkle-removing, freckle-removing and anti-aging composition is light yellow, spherical, with a particle size of 70-140 meshes, uniform particles, no adhesion, caking or moisture, and good fluidity. Comparative Example 1

[0043] The Rhus chinensis oil in the capsule core oil phase of Example 3 was replaced with soybean oil of the same mass, and the formula amounts and preparation methods of the remaining components were the same as those in Example 3. Comparative Example 2

[0044] Ellagic acid was not added to the capsule core oil phase, and the remaining components, amounts, and preparation methods were the same as those in Example 3. Example 7

[0045] 5 kg of each of the wrinkle-removing, freckle-removing, and anti-aging compositions of Experimental Examples 1-6 and the compositions of Comparative Examples 1 and 2 were weighed; each was prepared into 30,000 mL of emulsion, the pH of which was adjusted to 4-5 with a citric acid solution, and the emulsions were dispensed into 30 mL stick bags, for a total of 1,000 bags. The emulsions prepared with the microcapsules of the present invention exhibited excellent thermodynamic stability and storage stability, and did not delaminate over time. Example 8

[0046] 5 kg of the anti-wrinkle, anti-freckle, and anti-aging compositions of Experimental Examples 1-6 of the present invention and the compositions of Comparative Examples 1 and 2 were respectively weighed; β-cyclodextrin was added to each of them, and water was used as a wetting agent to prepare a soft material, sieved with a 20-mesh sieve to prepare wet granules, dried, and sized to obtain granules, which were then divided into strip bags with a specification of 10 g / bag, for a total of 1000 bags.

[0047] Experimental Example 1 Quality Evaluation of Anti-wrinkle, Anti-freckle and Anti-aging Compositions After grinding and pulverizing the microcapsules of Examples 1-6 and Comparative Example 1, 75 mg was accurately weighed and placed in a 100 mL volumetric flask. The mixture was soaked in a 50% mass concentration methanol solution for 1 hour and sonicated for 20 minutes to completely dissolve the ellagic acid. The volume was fixed with methanol solution, and the mixture was filtered through a 0.45 µm microporous membrane. The primary filtrate was discarded, and the subsequent filtrate was used for standby use. The peak area at 254 nm was measured by high performance liquid chromatography to calculate the ellagic acid concentration. After grinding and pulverizing the microcapsules of Examples 1-6 and Comparative Example 1, two samples were taken from each of them, and the average value was calculated.

[0048] The drug loading and encapsulation efficiency in the microcapsules were calculated. The results are shown in Table 1.

[0049] Drug loading = ellagic acid concentration × 100ml / 75mg × 100%.

[0050] Encapsulation efficiency = microcapsule mass × drug loading / dosage × 100%.

[0051] Table 1 Drug loading and encapsulation efficiency of the anti-wrinkle, anti-freckle and anti-aging compositions.

[0052] Group Ellagic acid concentration / mg / mL Drug loading rate / % Dosage / kg Microcapsule mass / kg Encapsulation efficiency / % Example 1 0.219 2.01% 0.3 14.5 97.33 Example 2 0.293 2.85% 0.4 13.7 97.67 Example 3 0.369 2.96% 0.5 16.6 98.40 Example 4 0.286 2.10% 0.4 18.2 95.33 Example 5 0.291 2.68% 0.4 14.5 97.00 Example 6 0.292 2.39% 0.4 16.3 97.33 Comparative Example 1 0.359 2.88% 0.5 16.6 95.73 The microcapsules prepared in Examples 1-6 of the present invention and Comparative Example 1 have good encapsulation quality, with an encapsulation efficiency of up to 95.33-98.40%, which is much higher than the encapsulation efficiency of more than 80% required by the pharmacopoeia.

[0053] Experimental Example 2 In vitro release test of anti-wrinkle, anti-freckle and anti-aging composition In vitro dissolution experiments were conducted according to the dissolution and release assay method described in General Chapter 0931 of the 2020 edition of the Chinese Pharmacopoeia (Volume IV). Artificial gastric fluid containing pepsin and artificial intestinal fluid at pH 6.8 containing trypsin were used as dissolution media. The solubility of ellagic acid was measured to simulate the dissolution rate of the anti-wrinkle, anti-freckle, and anti-aging composition in the human gastrointestinal tract.

[0054] Preparation method of artificial gastric juice: Take 16.4 mL of dilute hydrochloric acid, add about 800 mL of water and 10 g of pepsin, shake well, and dilute with water to 1000 mL.

[0055] Preparation method of artificial intestinal fluid: Take 6.8 g of potassium dihydrogen phosphate, add 500 mL of water to dissolve, and adjust the pH value to 6.8 with 0.1 mol / L sodium hydroxide solution; take 10 g of trypsin and 2 g of pancreatic lipase, dissolve them in water, mix the two liquids, and add water to make up to 1000 mL.

[0056] 0.075 g of the microcapsule powder prepared in Examples 1-6 and Comparative Example 1 was accurately weighed and dissolved in 500 mL of artificial gastric and intestinal fluid, respectively, in a 37°C water bath at 50 rpm. Samples were measured every 20 minutes and passed through a microporous filter. Ellagic acid concentration was used as the dissolution rate evaluation standard. Peak area (A) was measured at 254 nm using high-performance liquid chromatography (HPLC), and the concentration and dissolution rate were calculated. The results are shown in Tables 2 and 3.

[0057] Table 2 In vitro dissolution rate (%) of the anti-wrinkle, anti-freckle and anti-aging compositions in artificial gastric juice.

[0058] Group 20min 40min 60min 80 minutes 100min 120 minutes Example 1 0 0 0 0.28 1.36 5.24 Example 2 0 0 0 0.17 1.23 5.09 Example 3 0 0 0 0 1.05 4.12 Example 4 0 0 0 0 1.16 4.58 Example 5 0 0 0 0 1.27 4.64 Example 6 0 0 0 0 1.09 4.67 Comparative Example 1 0 0 0 0 1.18 4.81 Table 3 In vitro dissolution rate (%) of the anti-wrinkle, anti-freckle and anti-aging compositions in artificial intestinal fluid.

[0059] Group 20min 40min 60min 80 minutes 100min 120 minutes Example 1 65.52 79.43 93.68 99.54 99.91 100 Example 2 60.73 75.57 90.72 98.67 99.98 100 Example 3 56.32 73.34 90.41 98.89 99.78 100 Example 4 62.74 76.95 93.36 98.27 99.81 100 Example 5 61.13 71.15 91.47 97.62 99.72 100 Example 6 64.87 78.65 94.59 98.81 99.69 100 Comparative Example 1 55.63 70.28 88.74 98.54 99.79 100 From Table 2, Figure 1 It can be seen that the anti-wrinkle, anti-freckle and anti-aging compositions of Examples 1-6 and Comparative Example 1 did not dissolve in artificial gastric juice within 0-60 minutes, Examples 1 and 2 began to dissolve slightly at the 80th minute, and Examples 1-6 and Comparative Example 1 began to dissolve at the 100th minute.

[0060] From Table 3, Figure 2 It can be seen that the anti-wrinkle, anti-freckle and anti-aging compositions of Examples 1-6 and Comparative Example 1 have a solubility of more than 80% in artificial intestinal fluid at the 60th minute and are completely dissolved at the 120th minute, indicating good enteric solubility.

[0061] The wrinkle-removing, freckle-removing and anti-aging composition of the present invention does not dissolve in gastric juice and disintegrates only in the alkaline environment of the small intestine, which helps to reduce irritation to the stomach and ensures drug absorption in the small intestine.

[0062] Experimental Example 3 Animal Experiment on Anti-wrinkle, Anti-freckle and Anti-aging Composition One hundred one-month-old Kunming male mice, weighing 14±2g, were randomly divided into 10 groups of 10 mice each, namely, Examples 1-6, Comparative Examples 1 and 2, a healthy control group, and a model control group. The mice were housed at a normal temperature (23±2°C), humidity (55%±10%), and illumination (12 hours light / 12 hours dark, no UV exposure), with free access to food and water. After one week of feeding and acclimation, a hair removal area of ​​more than 2 cm x 3 cm was shaved on the back of the mice. Shave the hair once a week and apply 8% sodium sulfide solution to remove the hair. Mice in Examples 1-6, Comparative Examples 1 and 2, and the model control group received daily subcutaneous injections of D-galactose solution at the nape of the neck, combined with UV irradiation of the exposed skin on the back. The initial dose of D-galactose solution was 80 mg / kg / day subcutaneously injected at the nape of the neck for 7 consecutive days; the daily injection dose was 120 mg / kg / day from days 7 to 14, and 180 mg / kg / day from days 15 to 40. Before modeling, the UV lamp was preheated for 10 minutes. The cage was 30 cm away from the UV lamp, and the irradiation intensity was 0.35 mW / cm 2 Irradiation was performed twice daily, 30 minutes per session, with 12-hour intervals, for 40 consecutive days. Significant thickening, deep wrinkles, and sagging of the skin on the backs of the mice revealed signs of photoaging, demonstrating successful modeling of wrinkles and photoaging. The healthy group received daily injections of the same volume of saline without UV exposure. All injections were performed according to aseptic procedures.

[0063] The emulsion prepared in Example 7 of the present invention was administered orally twice daily to groups 1-6 and groups 1 and 2 of comparative examples, with an interval of 12 hours and a dose of 3 mL / kg / day. The healthy group and the model control group were administered orally twice daily with normal saline at a dose of 3 mL / kg / day. Administration was continued for 30 days.

[0064] After the experiment, the mice were killed, and 1 cm × 2 cm pieces of exposed skin were cut out. The wet weight was accurately weighed, and the skin was dried in an oven at 80°C for 12 h. The dry weight was weighed and the percentage of skin moisture content was calculated: Skin moisture percentage = (wet weight - dry weight) × 100% / wet weight.

[0065] Skin collagen content was determined by measuring hydroxyproline. Mouse skin was removed from the exposed skin, subcutaneous fat scraped off, and the skin was minced. 20 mg of mouse skin tissue was accurately weighed and placed in a 10 mL graduated test tube with a stopper. 2 mL of 6 mol / L hydrochloric acid solution was added and mixed thoroughly. The tube was sealed and acid-hydrolyzed at 125°C for 3 h. The pH was adjusted to 6, and the volume was made up to 10.0 mL with water. 0.1 mL of the hydrolyzed solution was then aspirated for hydroxyproline content using the chloramine T oxidation method. 0.1 g of mouse skin was homogenized in 1 mL of distilled water. 100 µL of the homogenate was aspirated for malondialdehyde content using the MDA-TBA colorimetric method. Malondialdehyde, a lipid peroxidation product, is an important indicator of aging and can reflect the degree of lipid peroxidation in tissues, indirectly reflecting the degree of cell damage. 800 µL of the sample was centrifuged at 10,000 rpm for 10 min at 4°C. The supernatant was then aspirated for SOD content using the pyrogallol autoxidation method. The experimental results are shown in Table 4. Figure 3 .

[0066] Table 4 Skin water content, hydroxyproline content, SOD activity and malondialdehyde content in different groups of mice.

[0067] Group Skin moisture content% Hydroxyproline content µg / mg SOD activity NU / mgprot Malondialdehyde content nmol / mgprot Example 1 group 67.43±2.52 48.64±3.84 140.19±18.61 4.17±0.67 Example 2 group 67.52±2.47 49.87±3.93 138.47±16.54 4.05±0.54 Example 3 group 67.84±2.53 53.57±3.56 147.49±17.31 3.79±0.63 Example 4 Group 67.31±2.62 52.82±4.08 143.74±18.49 3.82±0.56 Example 5 group 67.56±2.49 51.58±3.75 142.51±17.72 4.15±0.73 Example 6 67.49±2.65 51.97±3.92 140.78±18.53 3.96±0.64 Comparative Example 1 65.31±2.59 42.93±3.85 97.58±21.78 7.76±0.71 Comparative Example 2 62.73±2.57 35.87±3.86 82.83±22.57 10.13±0.82 Healthy Group 69.35±3.13 56.62±5.27 172.51±24.62 3.29±0.55 Model control group 59.97±2.86 31.13±3.42 62.74±18.73 12.68±1.25 Compared with the healthy group, the skin moisture content, hydroxyproline content and SOD activity of the model control group were significantly decreased, and the malondialdehyde content was significantly increased, with significant differences, and the model was successfully established. Compared with the model control group, the skin moisture content, hydroxyproline content and SOD activity of the embodiment 1-6 groups, the comparative example 1 and 2 groups were significantly increased, and the malondialdehyde content was significantly decreased, and the data were similar to the healthy group. It is illustrated that the embodiment 1-6 groups, the comparative example 1 and 2 groups have obvious repair and protective effects on the skin aging caused by ultraviolet light and D-galactose solution. The data of the embodiment 1-6 groups are respectively better than the comparative example 1 and 2 data, indicating that there is a synergistic effect between ellagic acid and Rhus chinensis oil in the wrinkle removal, freckle removal and anti-aging composition of the present invention.

[0068] The experimental results show that the microcapsules of the present invention can increase the SOD content and activity in mouse skin, scavenge free radicals, enhance the body's defense against photoaging, and prevent tissue and cell damage. They can also reduce the malondialdehyde content in mouse skin, preventing the destructive effects of harmful substances on tissue and cell structure and function, delaying aging and improving skin function.

[0069] Experimental Example 4 Experiment on the freckle removal function of the wrinkle-removing, freckle-removing and anti-aging composition 64 subjects with facial chloasma were selected on a voluntary basis. They were aged 18-65 years and randomly divided into 8 groups, namely Examples 1-6 and Comparative Examples 1 and 2. Diagnostic criteria: light brown or dark brown, clearly demarcated patches on the face, usually symmetrically distributed, without inflammatory manifestations or scaling, and without subjective symptoms such as pain or itching. There is a certain seasonality, with the symptoms being more severe in summer and milder in winter. The subjects took the oral solution prepared in Example 7 of the present invention daily for 45 consecutive days. The dosage was 30 mL / day. The subjects stopped taking or using any medications, health products, or cosmetics for removing chloasma during the experimental period.

[0070] Efficacy index: facial melasma area detection: use a ruler to measure the area of ​​chloasma on the entire face of the subject before and after (mm 2 ); Detection of the depth of facial melasma: According to the "Practical Standard Color Card" (first edition), the dark brown (yellow + magenta + black) color card is used as the judgment standard for the depth of melasma: degree I (15, 20, 5), degree II (30, 40, 10), degree III (40, 60, 15).

[0071] The chloasma color scores of the subjects were statistically analyzed, and the percentage of score reduction was calculated.

[0072] Percentage reduction of integral = (spot integral before the test - spot integral after the test) / spot area before the test Color card: Grade I, Grade II, and Grade III are scored as 1, 2, and 3 points respectively. The comparison results of the changes in the color and area of ​​chloasma are shown in Table 6. Figure 4 shown.

[0073] Table 6 Comparison of changes in color and area of ​​melasma (integral, X±S).

[0074] Group Before the experiment After the test Difference Points reduction percentage % Example 1 2.36±0.32 1.07±0.28 1.29 55.60 Example 2 2.43±0.33 0.89±0.26 1.54 63.37 Example 3 2.37±0.33 0.75±0.28 1.62 68.35 Example 4 2.36±0.35 0.84±0.25 1.52 64.41 Example 5 2.38±0.32 0.93±0.23 1.45 60.92 Example 6 2.42±0.36 1.02±0.26 1.40 57.85 Comparative Example 1 2.34±0.34 1.76±0.32 0.58 24.79 Comparative Example 2 2.46±0.32 2.13±0.29 0.33 13.41 From Table 6, Figure 4 It can be seen that the percentage reduction in chloasma score in Comparative Examples 1 and 2 was lower than that in Examples 1 to 6. This indicates that there is a synergistic effect between ellagic acid and Rhus chinensis oil, and the effect of ellagic acid and Rhus chinensis oil on chloasma removal when used together is greater than the sum of the effects of ellagic acid and Rhus chinensis oil alone.

[0075] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A wrinkle-removing, freckle-removing and anti-aging composition, characterized in that: The wrinkle-removing, freckle-removing and anti-aging composition is an enteric-coated microcapsule, comprising a capsule core oil phase and a capsule shell coated on the surface of the capsule core oil phase, wherein the capsule core oil phase comprises 0.3-0.5 parts by weight of ellagic acid and 2.4-2.8 parts by weight of Rhus chinensis oil; and the capsule shell comprises 4.0-8.0 parts by weight of arabinoxylan, 0.1-0.3 parts by weight of hydroxypropyl methylcellulose, 2.0-3.0 parts by weight of sodium alginate, 1.0-1.6 parts by weight of lactitol and 0.7-1.0 parts by weight of polyethylene glycol.

2. The wrinkle-removing, freckle-removing and anti-aging composition according to claim 1, characterized in that: The capsule shell further comprises 1.3-2.0 parts by weight of oligosaccharides.

3. The wrinkle-removing, freckle-removing and anti-aging composition according to claim 2, characterized in that: The oligosaccharide is one or more of fructooligosaccharide, xylooligosaccharide, isomaltooligosaccharide, soybean oligosaccharide and chitosan oligosaccharide.

4. The wrinkle-removing, freckle-removing and anti-aging composition according to claim 3, characterized in that: The capsule core oil phase includes 0.4 weight parts of ellagic acid and 2.6 weight parts of Rhus chinensis oil; the capsule skin includes 7.0 weight parts of arabinoxylan, 2.5 weight parts of sodium alginate, 1.5 weight parts of soybean oligosaccharides, 0.2 weight parts of hydroxypropyl methylcellulose, 1.5 weight parts of lactitol and 0.8 weight parts of polyethylene glycol.

5. A method for preparing the anti-wrinkle, anti-freckle and anti-aging composition according to any one of claims 1 to 4, characterized in that: The invention comprises the following steps: (S1) passing a formulated amount of ellagic acid through a 200-250 mesh sieve, ultrasonically suspending the ellagic acid in rhus chinensis oil, and obtaining a capsule core oil phase; (S2) adding a formulated amount of arabinoxylan, sodium alginate, hydroxypropyl methylcellulose, oligosaccharides, lactitol, and polyethylene glycol to 60-120 parts by weight of water, and mixing the mixture uniformly to obtain an aqueous phase; (S3) adding the oil phase to the aqueous phase and homogenizing the mixture to obtain an emulsion; and (S4) spray-freezing and drying the emulsion to obtain an anti-wrinkle, anti-freckle, and anti-aging composition.

6. The method for preparing the wrinkle-removing, freckle-removing and anti-aging composition according to claim 5, characterized in that: In (S3), emulsification and homogenization are carried out at 25°C, 25 MPa and a flow rate of 6 L / h.

7. The method for preparing the wrinkle-removing, freckle-removing and anti-aging composition according to claim 5, characterized in that: The spray drying conditions in (S4) were as follows: feeding rate of 2 mL / min, inlet temperature of 180 °C, outlet temperature of 90 °C, nozzle atomization pressure of 0.4 MPa, and fan power of 10 m 3 / min, and then freeze-dried to make the finished product.

8. An oral pharmaceutical preparation, characterized in that: The invention comprises the wrinkle-removing, freckle-removing and anti-aging composition according to any one of claims 1 to 4 and pharmaceutically acceptable oral preparation excipients, wherein the dosage form of the drug is granules, tablets, capsules, powders, pills, emulsions or suspensions.

9. Use of the wrinkle-removing, freckle-removing and anti-aging composition according to any one of claims 1 to 4 in the preparation of health-care foods for wrinkle-removing, freckle-removing and anti-aging.

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