Wrinkle-, spot-, and anti-aging compositions and methods of making same

Abstract

The application belongs to the technical field of medicine 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 coated on the surface of the capsule core oil phase, wherein the capsule core oil phase comprises tannic acid and pistachio nut oil; and the capsule skin comprises arabinoxylan, hydroxypropyl methyl cellulose, sodium alginate, lactitol and polyethylene glycol. The wrinkle-removing, freckle-removing and anti-aging composition has the advantages of small side effect of tannic acid, high bioavailability, synergistic effect of tannic acid and pistachio nut oil and good wrinkle-removing, freckle-removing and anti-aging effect.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and in particular relates to a wrinkle-removing, spot-removing, and anti-aging composition and its preparation method. Background Technology

[0002] Skin is easily affected by factors such as age, environment, genetics, diet, and sun exposure, leading to aging. If the skin is subjected to oxidation for a long time, does not receive proper care, or if the body's APSC pluripotent cells decline with age, dead skin will adhere to the skin surface and not shed, causing a series of problems and seriously affecting appearance. This is the process of skin aging.

[0003] Wrinkles are a major sign of skin aging. Most facial wrinkles are caused by frequent facial muscle movements, leading to repeated stretching and folding of the skin. Some fine wrinkles are caused by the aging process over time, resulting in the breakage of elastic fibers and the loss of collagen in the superficial dermis. This loss of the network structure formed by elastic fibers, collagen, and collagen fibers in the superficial dermis also contributes to the formation of fine wrinkles. Skin aging can also cause abnormal melanin metabolism, leading to the accumulation of melanin in the epidermis and the formation of age spots.

[0004] Ellagic acid is a natural phenolic antioxidant widely found in many fruits and vegetables, including blackberries, raspberries, strawberries, cranberries, pecans, pomegranates, and goji berries. Ellagic acid possesses a wide range of pharmacological activities, and its potential health benefits are receiving increasing attention, such as anti-inflammatory, antioxidant, anti-tumor, cardiovascular protection, organ protection, blood sugar regulation, and antibacterial effects. The antioxidant activity of ellagic acid can be used for wrinkle reduction, blemish removal, and anti-aging.

[0005] Ellagic acid is a natural antioxidant that effectively scavenge free radicals in the body, such as oxygen free radicals and hydroxyl free radicals. Free radicals are a major factor leading to oxidative damage to cells and accelerating aging. Ellagic acid reduces the attack of free radicals on cells by scavenging them, thereby protecting cell structure and function and delaying cell aging. Ellagic acid can also inhibit lipid peroxidation induced by acetaminophen and lipid peroxidation caused by exogenous substances in tissues. Lipid peroxidation leads to cell membrane damage and affects normal cell function. Ellagic acid protects the integrity of cell membranes and maintains normal cellular physiological activities by inhibiting lipid peroxidation. Ellagic acid can promote collagen synthesis, enhance skin elasticity, reduce wrinkles, and keep skin youthful. Ellagic acid can inhibit tyrosinase activity, reduce melanin production, thereby helping to lighten dark spots, brighten skin tone, make skin whiter, improve skin appearance, and delay skin aging.

[0006] Ellagic acid has a water solubility of only 9.81 μg / mL, resulting in extremely low dissolution rate and degree. It also has poor lipid solubility, making it difficult to transmembrane transport into the bloodstream, leading to low bioavailability. The digestion and absorption of ellagic acid primarily occur in the intestines. A small portion is directly absorbed into the bloodstream by the small intestinal epithelial cells, while the majority is converted into urolithin, a more bioavailable form, through lactone ring cleavage, decarboxylation, and dehydroxylation reactions by beneficial intestinal bacteria. As its lipophilicity increases, it is then transported into the bloodstream via intestinal epithelial cells. If taken orally, ellagic acid combines with pepsin under acidic conditions (pH 1-2) to form an indigestible complex that remains in the stomach, affecting digestion and causing symptoms such as bloating and abdominal pain. It may also form bezoars. Ellagic acid's astringent properties can also lead to excessive water absorption in the gastrointestinal tract, slowing peristalsis and causing side effects such as constipation, nausea, and dizziness.

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

[0008] This invention proposes a wrinkle-removing, freckle-removing, and anti-aging composition with few side effects and high bioavailability, as well as its preparation method.

[0009] A wrinkle-reducing, blemish-removing, and anti-aging composition includes a core oil phase and a capsule shell coating the surface of the core oil phase. The core oil phase includes 0.3-0.5 parts by weight of ellagic acid and 2.4-2.8 parts by weight of sumac fruit oil. The capsule shell includes 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 raspberry, gallnut, blackberry or pomegranate peel.

[0011] This invention prepares ellagic acid into enteric-coated microcapsules, avoiding the side effects of ellagic acid irritating the gastrointestinal tract. In the low pH environment of the stomach, the capsule shell of the enteric-coated microcapsule swells, forming a gel. In the high pH environment of the intestine, the gel decomposes into oligosaccharides or polysaccharides, and the oil phase of the capsule core is slowly released. The capsule shell and sumac fruit oil enhance the activity of intestinal flora, increase the rate of ellagic acid conversion to urolithin, and improve the bioavailability of ellagic acid.

[0012] Sumac fruit oil is a yellow, transparent, oily liquid produced from sumac fruit through processes such as air explosion, pressing, extraction, and filtration. Sumac fruit oil contains various unsaturated fatty acids, phytosterols, vitamin E, and polyphenolic phytochemicals. It not only improves the metabolic efficiency of beneficial intestinal bacteria and promotes the conversion of ellagic acid into urolithin-like substances, but its unsaturated fatty acids also enhance the absorption efficiency of urolithin-like substances and improve the bioavailability of ellagic acid. The abundant polyphenols in sumac fruit oil can inhibit tyrosinase activity, reduce melanin production, and have excellent whitening and spot-removing effects. The phytosterols in sumac fruit oil can prevent collagen breakdown, stimulate collagen production, promote the recovery of skin elasticity and structure, and reduce and prevent skin aging and wrinkles caused by ultraviolet radiation. The combination of ellagic acid and sumac fruit oil has a synergistic effect.

[0013] Sodium alginate and arabinoxylan are mixed as components of the capsule shell, forming a composite gel with a dense three-dimensional network 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 down the release rate of ellagic acid. This provides a stable blood drug concentration, avoiding gastrointestinal irritation and side effects (hypertension, dizziness, nausea) caused by a sudden increase in ellagic acid concentration. Furthermore, the capsule shell has a sustained-release effect, prolonging the release time of ellagic acid in the digestive tract, improving the absorption efficiency of ellagic acid, and increasing its bioavailability.

[0014] Arabicoxylan can be broken down into arabinoxylose by intestinal microorganisms. As a prebiotic, arabinoxylose enhances the metabolic activity of intestinal flora. Hydroxypropyl methylcellulose (HMCMC) contributes to the uniform particle size distribution of the oil phase in the microcapsule preparation process, resulting in microcapsule particles of uniform size. As a component of the capsule shell, HMCMC fills the gaps between arabinoxylan, preventing gastric acid penetration and protecting the oil phase of the capsule core from gastric acid. Lactitol regulates the intestinal microecology, effectively protecting the balance of the intestinal microecological system. It can directly or indirectly regulate the composition of beneficial and harmful bacteria in the gut, selectively inhibiting pathogenic bacteria, promoting the growth of beneficial bacteria, optimizing the intestinal flora structure, enhancing the metabolic activity of intestinal flora, and promoting the conversion of ellagic acid to urolithin-like substances. Lactitol also promotes intestinal peristalsis, avoiding the constipation and other side effects caused by the astringent effect of ellagic acid.

[0015] The capsule also includes 1.3-2.0 parts by weight of oligosaccharides.

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

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

[0018] The core oil phase comprises 0.4 parts by weight of ellagic acid and 2.6 parts by weight of sumac fruit oil; the outer shell comprises 7 parts by weight of arabinoxylan, 2.5 parts by weight of sodium alginate, 1.5 parts by weight of soybean oligosaccharides, 0.2 parts by weight of hydroxypropyl methylcellulose, 1.5 parts by weight of lactitol and 0.8 parts by weight of polyethylene glycol.

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

[0020] In (S3), emulsification and homogenization are carried out at 25℃, 25MPa and a flow rate of 6L / h.

[0021] (S4) The spray freeze-drying conditions are: feed rate of 2 mL / min, inlet temperature of 180℃, outlet temperature of 90℃, nozzle atomization pressure of 0.4 MPa, and fan power of 10 m³ / min. 3 The product is processed at a rate of 1000 m / min and then freeze-dried to produce the final product.

[0022] An oral pharmaceutical preparation comprising the aforementioned anti-wrinkle, anti-spot, and anti-aging composition and pharmaceutically acceptable oral formulation excipients, wherein the dosage form of the pharmaceutical preparation is granules, tablets, capsules, powders, pills, emulsions, or suspensions.

[0023] Optionally, the excipients for the oral formulation 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 application of the aforementioned wrinkle-reducing, blemish-reducing, and anti-aging composition in the preparation of health foods for wrinkle reduction, blemish reduction, and anti-aging.

[0025] This invention's anti-wrinkle, anti-spot, and anti-aging composition utilizes an enteric-coated microcapsule formulation, avoiding the formation of indigestible complexes from ellagic acid binding with proteins under low pH conditions, thus preventing side effects such as bloating and abdominal pain associated with ellagic acid. The antioxidant components in sumac fruit oil improve the conversion rate of ellagic acid into absorbable urolithin-like substances by regulating the metabolic capacity of intestinal flora. The unsaturated fatty acids in sumac fruit oil enhance the efficiency of urolithin-like substances entering the bloodstream through intestinal epithelial cells, thereby improving the bioavailability of ellagic acid. The synergistic effect of ellagic acid and sumac fruit oil in the anti-wrinkle and anti-aging enteric-coated microcapsules of this invention inhibits tyrosinase activity, blocks melanin production, and has anti-spot and whitening effects. It effectively promotes the regeneration of skin elastic fibers and collagen, prevents the degradation of elastic fibers and collagen, and especially reduces skin tissue damage caused by long-term or frequent radiation and ultraviolet radiation from sunlight, slowing down photoaging and exhibiting excellent anti-wrinkle, anti-spot, and anti-aging effects. Attached Figure Description

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

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

[0028] Figure 3 This is a bar chart showing the skin moisture content, hydroxyproline content, SOD activity, and malondialdehyde content of mice in different groups during animal experiments of the wrinkle-removing, spot-removing, and anti-aging composition of Experiment 3 of the present invention.

[0029] Figure 4 This is a bar chart showing the percentage reduction in melasma score in a clinical trial of the anti-wrinkle, anti-spot, and anti-aging composition of Experiment Example 4 of this invention. Detailed Implementation Example 1

[0030] (S1) 0.4 kg of ellagic acid was passed through a 200-mesh sieve and added to 2.4 kg of sumac fruit oil. The mixture was ultrasonically suspended and thoroughly mixed to obtain the 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 and thoroughly mixed to obtain the aqueous phase. (S3) The oil phase was added to the aqueous phase and emulsified and homogenized at 25℃, 25 MPa, and a flow rate of 6 L / h to obtain an emulsion. (S4) The emulsion was spray-dried to obtain a wrinkle-reducing, spot-removing, and anti-aging composition. The spray-drying conditions were: feed rate of 2 mL / min, inlet temperature of 180℃, outlet temperature of 90℃, nozzle atomization pressure of 0.4 MPa, and fan power of 10 m³ / min.3 The product is processed at a rate of 1000 m / min and then freeze-dried to produce the final product.

[0031] The anti-wrinkle, anti-spot, and anti-aging composition is light yellow, spherical, with a particle size of 70-140 mesh. The particles are uniform, without sticking, clumping, or dampness, and have good fluidity. Example 2

[0032] (S1) 0.4 kg of ellagic acid was passed through a 250-mesh sieve and added to 2.6 kg of sumac fruit oil. The mixture was ultrasonically suspended and thoroughly mixed to obtain the 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 and thoroughly mixed to obtain the aqueous phase. (S3) The oil phase was added to the aqueous phase and emulsified and homogenized at 25℃, 25 MPa, and a flow rate of 6 L / h to obtain an emulsion. (S4) The emulsion was spray-dried to obtain a wrinkle-reducing, spot-removing, and anti-aging composition. The spray-drying conditions were: a feeding rate of 2 mL / min, an inlet temperature of 180℃, an outlet temperature of 90℃, a nozzle atomization pressure of 0.4 MPa, and a fan power of 10 m³ / min. 3 The product is processed at a rate of 1000 m / min and then freeze-dried to produce the final product.

[0033] The anti-wrinkle, anti-spot, and anti-aging composition is light yellow, spherical, with a particle size of 70-140 mesh. The particles are uniform, without sticking, clumping, or dampness, and have good fluidity. Example 3

[0034] (1) Pass 0.5 kg of ellagic acid through a 250-mesh sieve and add it to 2.6 kg of sumac fruit oil for ultrasonic suspension. Mix evenly to obtain the core oil phase.

[0035] (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;

[0036] (3) The oil phase was added to the aqueous phase and emulsified and homogenized at 25℃, 25MPa and a flow rate of 6L / h to obtain an emulsion;

[0037] (4) The emulsion was spray-dried to obtain an anti-wrinkle, anti-spot, and anti-aging composition. The spray-drying conditions were: feeding rate of 2 mL / min, inlet temperature of 180℃, outlet temperature of 90℃, nozzle atomization pressure of 0.4 MPa, and fan power of 10 m³ / min. 3 The product is processed at a rate of 1000 m / min and then freeze-dried to produce the final product.

[0038] The anti-wrinkle, anti-spot, and anti-aging composition is light yellow, spherical, with a particle size of 70-140 mesh. The particles are uniform, without sticking, clumping, or dampness, and have good fluidity. Example 4

[0039] (S1) 0.4 kg of ellagic acid was passed through a 200-mesh sieve and added to 2.8 kg of sumac fruit oil. The mixture was ultrasonically suspended and thoroughly mixed to obtain the 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 xylooligosaccharides, 0.5 kg of chitosan oligosaccharides, 1.5 kg of lactitol, and 1.0 kg of polyethylene glycol were added to 120 L of water and thoroughly mixed to obtain the aqueous phase. (S3) The oil phase was added to the aqueous phase and emulsified and homogenized at 25℃, 25 MPa, and a flow rate of 6 L / h to obtain an emulsion. (S4) The emulsion was spray-dried to obtain a wrinkle-reducing, spot-removing, and anti-aging composition. The spray-drying conditions were: a feeding rate of 2 mL / min, an inlet temperature of 180℃, an outlet temperature of 90℃, a nozzle atomization pressure of 0.4 MPa, and a fan power of 10 m³ / min. 3 The product is processed at a rate of 1000 m / min and then freeze-dried to produce the final product.

[0040] The anti-wrinkle, anti-spot, and anti-aging composition is light yellow, spherical, with a particle size of 70-140 mesh. The particles are uniform, without sticking, clumping, or dampness, and have good fluidity. Example 5

[0041] (S1) 0.4 kg of ellagic acid was passed through a 250-mesh sieve and added to 2.6 kg of sumac fruit oil. The mixture was ultrasonically suspended and thoroughly mixed to obtain the 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 xylooligosaccharides, 0.5 kg of chitosan oligosaccharides, 0.5 kg of isomaltooligosaccharides, 1.6 kg of lactitol, and 0.8 kg of polyethylene glycol were added to 80 L of water and thoroughly mixed to obtain the aqueous phase. (S3) The oil phase was added to the aqueous phase and emulsified and homogenized at 25℃, 25 MPa, and a flow rate of 6 L / h to obtain an emulsion. (S4) The emulsion was spray-dried to obtain a wrinkle-reducing, spot-removing, and anti-aging composition. The spray-drying conditions were: a feeding rate of 2 mL / min, an inlet temperature of 180℃, an outlet temperature of 90℃, a nozzle atomization pressure of 0.4 MPa, and a fan power of 10 m³ / min. 3 The product is processed at a rate of 1000 m / min and then freeze-dried to produce the final product.

[0042] The anti-wrinkle, anti-spot, and anti-aging composition is light yellow, spherical, with a particle size of 70-140 mesh. The particles are uniform, without sticking, clumping, or dampness, and have good fluidity. Example 6

[0043] (S1) 0.4 kg of ellagic acid was passed through a 250-mesh sieve and added to 2.8 kg of sumac fruit oil. The mixture was ultrasonically suspended and thoroughly mixed to obtain the 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 xylooligosaccharides, 0.8 kg of chitosan oligosaccharides, 0.4 kg of fructooligosaccharides, 1.6 kg of lactitol, and 0.9 kg of polyethylene glycol were added to 90 L of water and thoroughly mixed to obtain the aqueous phase. (S3) The oil phase was added to the aqueous phase and emulsified and homogenized at 25℃, 25 MPa, and a flow rate of 6 L / h to obtain an emulsion. (S4) The emulsion was spray-dried to obtain a wrinkle-reducing, spot-removing, and anti-aging composition. The spray-drying conditions were: a feeding rate of 2 mL / min, an inlet temperature of 180℃, an outlet temperature of 90℃, a nozzle atomization pressure of 0.4 MPa, and a fan power of 10 m³ / min. 3 The product is processed at a rate of 1000 m / min and then freeze-dried to produce the final product.

[0044] The anti-wrinkle, anti-spot, and anti-aging composition is light yellow, spherical, with a particle size of 70-140 mesh. The particles are uniform, without sticking, clumping, or dampness, and have good fluidity. Comparative Example 1

[0045] The sumac fruit oil in the core oil phase of Example 3 was replaced with the same mass of soybean oil, while the formulation and preparation method of the remaining components were the same as in Example 3. Comparative Example 2

[0046] Ellagic acid was not added to the oil phase of the capsule core, and the formulation and preparation method of the remaining components were the same as in Example 3. Example 7

[0047] Weigh out 5 kg each of the wrinkle-removing, spot-removing, and anti-aging compositions of Experimental Examples 1-6 and Comparative Examples 1 and 2; prepare 30,000 mL emulsions for each, adjust the pH to 4-5 using citric acid solution, and dispense into 30 mL packets, totaling 1000 packets. The emulsions prepared by the microcapsules of this invention exhibit good thermodynamic stability, good storage stability, and do not separate into layers even after prolonged storage. Example 8

[0048] Weigh out 5 kg each of the wrinkle-removing, spot-removing, and anti-aging compositions of Experimental Examples 1-6 of the present invention and the compositions of Comparative Examples 1 and 2; add β-cyclodextrin to each, use water as a wetting agent to make a soft material, sieve through a 20-mesh screen to form wet granules, dry, granulate, and obtain granules, which are then divided into strip packets with a specification of 10g / packet, for a total of 1000 packets.

[0049] Experimental Example 1: Quality Evaluation of Anti-wrinkle, Anti-spot, and Anti-aging Compositions

[0050] Each of the microcapsules from Examples 1-6 and Comparative Example 1 was ground and 75 mg was accurately weighed and placed in a 100 mL volumetric flask. The flask was then soaked in a 50% methanol solution for 1 hour and sonicated for 20 minutes to completely dissolve the ellagic acid. The solution was then diluted to volume with methanol and filtered through a 0.45 µm microporous membrane. The initial filtrate was discarded, and the subsequent filtrate was collected for later use. The peak area at 254 nm was determined using high-performance liquid chromatography (HPLC), and the ellagic acid concentration was calculated. Samples of each of the microcapsules from Examples 1-6 and Comparative Example 1 were taken twice after grinding and pulverizing, and the average value was taken.

[0051] The drug loading rate and encapsulation efficiency in the microcapsules were calculated. The results are shown in Table 1.

[0052] Drug loading rate = ellagic acid concentration × 100ml / 75mg × 100%.

[0053] Encapsulation efficiency = Microcapsule mass × Drug loading rate / Drug dosage × 100%.

[0054] Table 1. Drug loading rate and encapsulation rate of anti-wrinkle, anti-spot, and anti-aging compositions.

[0055] Group Drug loading rate / % Dosage / kg Microcapsule mass / kg Encapsulation rate / % Example 1 2.01 0.3 14.5 97.33 Example 2 2.85 0.4 13.7 97.67 Example 3 2.96 0.5 16.6 98.40 Example 4 2.10 0.4 18.2 95.33 Example 5 2.68 0.4 14.5 97.00 Example 6 2.39 0.4 16.3 97.33 Comparative Example 1 2.88 0.5 16.6 95.73

[0056] The microcapsules prepared in Examples 1-6 and Comparative Example 1 of this invention have good encapsulation quality, with an encapsulation rate as high as 95.33-98.40%, which is much higher than the encapsulation rate of more than 80% required by the pharmacopoeia.

[0057] Experiment Example 2: In vitro release rate experiment of anti-wrinkle, anti-spot, and anti-aging composition

[0058] In vitro dissolution experiments were conducted according to the Dissolution and Release Assay Method in General Chapter 0931 of the 2020 edition of the Chinese Pharmacopoeia (Part IV). Artificial gastric juice containing pepsin and artificial intestinal juice containing trypsin at pH 6.8 were used as dissolution media to simulate the dissolution rate of the anti-wrinkle, anti-spot, and anti-aging compositions in the human gastrointestinal tract by detecting the dissolution rate of ellagic acid.

[0059] Preparation method of artificial gastric fluid: Take 16.4 mL of dilute hydrochloric acid, add about 800 mL of water and 10 g of pepsin, shake well, and then dilute with water to a final volume of 1000 mL.

[0060] Preparation method of artificial intestinal fluid: Dissolve 6.8g of potassium dihydrogen phosphate in 500mL of water, and adjust the pH to 6.8 with 0.1mol / L sodium hydroxide solution; separately dissolve 10g of trypsin and 2g of pancreatic lipase in water, mix the two solutions, and add water to make up to 1000mL.

[0061] 0.075 g of the microcapsule powder prepared in Examples 1-6 and Comparative Example 1 of this invention was accurately weighed and dissolved in 500 mL of simulated gastric and intestinal fluids at 37°C and 50 r / min, respectively. Samples were measured every 20 min and filtered through a microporous membrane. Ellagic acid concentration was used as the evaluation standard for dissolution rate. The peak area A at 254 nm was determined by high performance liquid chromatography (HPLC), and the concentration and dissolution rate were calculated. The results are shown in Tables 2 and 3.

[0062] Table 2. In vitro dissolution rate of the anti-wrinkle, anti-spot, and anti-aging composition in artificial gastric juice.

[0063] Group 20min 40min 60min 80min 100min 120min 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

[0064] Table 3. In vitro dissolution rate of the anti-wrinkle, anti-spot, and anti-aging composition in artificial intestinal fluid.

[0065] Group 20min 40min 60min 80min 100min 120min 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

[0066] From Table 2, Figure 1 As can be seen, the anti-wrinkle, anti-spot, and anti-aging compositions of Examples 1-6 and Comparative Example 1 did not dissolve within 0-60 minutes in artificial gastric juice, while Examples 1 and 2 began to dissolve in trace amounts at 80 minutes, and Examples 1-6 and Comparative Example 1 began to dissolve at 100 minutes.

[0067] From Table 3, Figure 2 As can be seen, the anti-wrinkle, anti-spot, and anti-aging compositions of Examples 1-6 and Comparative Example 1 achieved a dissolution rate of over 80% in artificial intestinal fluid at 60 minutes. Complete dissolution was achieved at 120 minutes, demonstrating good enteric solubility.

[0068] The wrinkle-reducing, blemish-removing, and anti-aging composition of this invention does not dissolve in gastric juice but disintegrates only in the alkaline environment of the small intestine, which helps reduce stomach irritation and ensures drug absorption in the small intestine.

[0069] Experiment Example 3: Animal Experiment of Anti-wrinkle, Anti-spot, and Anti-aging Combinations

[0070] One hundred one-month-old male Kunming mice, weighing 14±2g, were randomly divided into 10 groups of 10 mice each: Examples 1-6, Comparative Examples 1 and 2, a healthy group, and a model control group. Mice were fed at normal temperature (23±2℃), humidity (55%±10%), and light conditions (12 hours light / 12 hours darkness, no UV exposure), with free access to food and water. After one week of feeding, once the mice had adapted to the environment, a hairless area exceeding 2cm × 3cm was shaved on the back of each mouse. Shaving was performed weekly, and the downy hair was removed using an 8% sodium sulfide solution. Mice in Examples 1-6, Comparative Examples 1 and 2, and the model control group received daily subcutaneous injections of D-galactose solution into the neck and back, combined with UV exposure of the exposed skin on their backs. The initial subcutaneous injection of D-galactose solution into the neck and back was 80 mg / kg / day 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. The UV lamp was preheated for 10 minutes before modeling. The rat cage was placed 30 cm away from the UV lamp, with an irradiance of 0.35 mW / cm². 2 The mice were irradiated twice daily for 30 minutes each time, with a 12-hour interval, for 40 consecutive days. Significant thickening, deep wrinkles, and sagging skin—symptoms of photoaging—appeared on the backs of the mice, indicating successful establishment of the photoaging model. The healthy group received the same volume of saline solution daily and did not receive ultraviolet light treatment. All injections were performed under aseptic conditions.

[0071] The emulsion prepared in Example 7 of this invention was used in the following groups: Examples 1-6, Comparative Examples 1 and 2, and the oral solution was administered orally twice daily with an interval of 12 hours. The oral dose was 3 mL / kg / day. The healthy group and the model control group were administered physiological saline twice daily with a dose of 3 mL / kg / day. The administration was continued for 30 days.

[0072] After the experiment, the mice were euthanized, and a 1cm × 2cm piece of bare skin was cut off. The wet weight was accurately weighed, and the skin was dried in an oven at 80℃ for 12 hours. The dry weight was then measured, and the percentage of skin moisture content was calculated.

[0073] Skin moisture content percentage = (wet weight - dry weight) × 100% / wet weight.

[0074] The content of skin collagen was determined by measuring the hydroxyproline content. Exposed mouse skin was excised, subcutaneous fat was scraped off, and the tissue was cut into small pieces. 20 mg of mouse skin tissue was accurately weighed and placed in a 10 mL stoppered graduated test tube. 2 mL of 6 mol / L hydrochloric acid solution was added, mixed, sealed, and incubated at 125℃ for 3 hours. The pH was adjusted to 6, and water was added to a final volume of 10.0 mL. 0.1 mL of the hydrolysate was taken and the hydroxyproline content was determined using the chloramine-T oxidation method. 0.1 g of exposed mouse skin was taken and homogenized with 1 mL of distilled water. 100 µL of the homogenate was taken and the malondialdehyde (MDA) content was determined using the MDA-TBA colorimetric method. MDA, as a lipid peroxidation product, is an important indicator of aging and reflects the degree of lipid peroxidation in tissues, indirectly reflecting the degree of cell damage. 800 µL of the supernatant was centrifuged at 10000 r / min for 10 min at 4℃, and the SOD content was determined using the pyrogallol autoxidation method. The experimental results are shown in Table 4. Figure 3 .

[0075] Table 4. Skin water content, hydroxyproline content, SOD activity, and malondialdehyde content of mice in different groups.

[0076] 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 group 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 Health 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

[0077] Compared with the healthy group, the model control group showed a significant decrease in skin moisture content, hydroxyproline content, and SOD activity, and a significant increase in malondialdehyde content, indicating a successful model establishment. Compared with the model control group, the skin moisture content, hydroxyproline content, and SOD activity of Examples 1-6 and Comparative Examples 1 and 2 were significantly increased, while malondialdehyde content was significantly decreased, with data similar to the healthy group. This demonstrates that Examples 1-6 and Comparative Examples 1 and 2 have significant repair and protective effects against skin aging induced by ultraviolet radiation and D-galactose solution. The data from Examples 1-6 are superior to those from Comparative Examples 1 and 2, indicating a synergistic effect between ellagic acid and sumac fruit oil in the wrinkle-reducing, spot-removing, and anti-aging composition of this invention.

[0078] The results of this experiment 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 damage to tissue cells. They can also reduce the malondialdehyde content in mouse skin, preventing harmful substances from damaging the structure and function of tissue cells, delaying aging, and improving skin function.

[0079] Experiment Example 4: Anti-wrinkle, anti-spot, and anti-aging composition; anti-spot function in a population experiment.

[0080] Sixty-four individuals aged 18-65 years with facial melasma were selected as subjects on a voluntary basis and randomly divided into eight groups: Examples 1-6, and Comparative Examples 1 and 2. Diagnostic criteria: well-defined, light or dark brown patches on the face, usually symmetrically distributed, without inflammation or scaling, and without subjective symptoms such as pain or itching. The condition showed some seasonality, being more severe in summer and milder in winter. Subjects took the oral liquid prepared in Example 7 of this invention daily for 45 consecutive days. The dosage was 30 mL / day. Subjects discontinued all use of any medications, health products, or cosmetics related to the removal of melasma during the experiment.

[0081] Efficacy Indicator: Measurement of the area of ​​melasma on the face: The area of ​​melasma on the subject's entire face before and after treatment was measured using a ruler (mm²). 2 ); Detection of the depth of color of melasma on the face: According to the "Practical Standard Color Card" (first edition), the dark brown (yellow + magenta + black) color card is used as the standard for judging the depth of melasma: I degree (15, 20, 5), II degree (30, 40, 10), III degree (40, 60, 15).

[0082] The scores of the subjects' melasma color were statistically analyzed, and the percentage reduction in scores was calculated.

[0083] Percentage reduction in integral = (Integral score of chroma before test - Integral score of chroma after test) / Integral score of chroma before test

[0084] Color chart: Level I, Level II, and Level III are scored as 1, 2, and 3 points respectively. The comparison results of the color and area changes of chloasma are shown in Table 6. Figure 4 As shown.

[0085] Table 6 Comparison of changes in color and area of ​​chloasma (integral, X±S).

[0086] 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

[0087] From Table 6, Figure 4 It can be seen that the percentage reduction in melasma scores in Comparative Examples 1 and 2 is lower than that in Examples 1-6. This indicates a synergistic effect between ellagic acid and sumac fruit oil; the combined effect of ellagic acid and sumac fruit oil in removing melasma is greater than the sum of the effects of using ellagic acid and sumac alone.

[0088] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A composition for wrinkle, spot, and anti-aging, characterized by: The anti-wrinkle, anti-melasma and anti-aging composition is an enteric microcapsule, comprising 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 commiphora oil; 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, 0.7-1.0 parts by weight of polyethylene glycol and 1.3-2.0 parts by weight of oligosaccharide; and the anti-wrinkle, anti-melasma and anti-aging composition is prepared by the following method: (S1) sieving the ellagic acid of the formula amount through a 200-250 mesh sieve, and ultrasonically suspending the ellagic acid into the commiphora oil to obtain the capsule core oil phase; (S2) adding the arabinoxylan, sodium alginate, hydroxypropyl methylcellulose, oligosaccharide, lactitol and polyethylene glycol of the formula amount into 60-120 parts by weight of water, and mixing uniformly to obtain an aqueous phase; (S3) adding the oil phase into the aqueous phase, and homogenizing to obtain an emulsion; and (S4) spray drying the emulsion, and freeze drying to obtain the anti-wrinkle, anti-melasma and anti-aging composition.

2. Wrinkle-, spot-, and anti-aging composition according to claim 1, characterized in that: The oligosaccharide is one or more of fructooligosaccharide, xylooligosaccharide, isomaltooligosaccharide, soybean oligosaccharide and chitosan oligosaccharide.

3. The anti-wrinkle, anti-stain, anti-aging composition according to claim 1, characterized in that: The capsule core oil phase comprises 0.4 parts by weight of ellagic acid and 2.6 parts by weight of commiphora oil; and the capsule skin comprises 7.0 parts by weight of arabinoxylan, 2.5 parts by weight of sodium alginate, 1.5 parts by weight of soybean oligosaccharide, 0.2 parts by weight of hydroxypropyl methylcellulose, 1.5 parts by weight of lactitol and 0.8 parts by weight of polyethylene glycol.

4. The anti-wrinkle, anti-spot, anti-aging composition according to claim 1, characterized in that: In (S3), the emulsification and homogenization are carried out at 25℃, 25MPa and a flow rate of 6L / h.

5. Wrinkle-, spot-, and anti-aging composition according to claim 4, characterized in that: The spray drying conditions in (S4) are as follows: feeding speed 2 mL / min, inlet temperature 180 ℃, outlet temperature 90 ℃, nozzle atomization pressure 0.4 MPa, and fan power 10 m 3 / min. The product is prepared after freeze drying.

6. An oral pharmaceutical preparation, characterized by: The anti-wrinkle, anti-melasma and anti-aging composition of any one of claims 1-5 and a pharmaceutically acceptable oral preparation auxiliary are included, and the dosage form of the medicine is granules, tablets, capsules, powder, pills, emulsion or suspension.

7. Use of the anti-wrinkle, anti-melasma and anti-aging composition of any one of claims 1-5 in the preparation of a health food for anti-wrinkle, anti-melasma and anti-aging.

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