Preparation and application of cyclodextrin-coated azelaic acid oil-control skin-care product

Abstract

The invention relates to the technical field of cosmetics, in particular to preparation and application of a cyclodextrin-coated azelaic acid oil-control skin-care product. Comprising the following steps: S1, adding deionized water into a mixer, adding a cyclodextrin-azelaic acid inclusion compound, nicotinamide and allantoin, mixing to obtain a water phase, mixing glycerol, caprylic / capric triglyceride, polydimethylsiloxane, polysorbate-80 and tocopheryl acetate to obtain an oil phase, slowly adding the oil phase into the water phase, and shearing and emulsifying to obtain a nanoemulsion; and S2, cooling the nano-emulsion, adding carbomer while stirring, continuously cooling to room temperature, sequentially adding phenoxyethanol, ferulic acid, menthol and essence, adjusting the pH value of the emulsion with triethanolamine, homogenizing, defoaming, disinfecting and filling. By adjusting the proportion of the components in the formula, the skin feeling of the product can be further optimized, so that the product is more comfortable and not greasy, and a lasting oil control effect is provided.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, and particularly to the preparation and application of a cyclodextrin-encapsulated azelaic acid oil-control skin care product. Background Art

[0002] Oily skin is prone to problems such as pore blockage, frequent acne, and greasy skin due to the excessive secretion of sebaceous glands, which brings many inconveniences and troubles to people's lives. Oil-control skin care products refer to those skin care products that can effectively reduce the secretion of skin oil and improve oily skin problems. Such products help the skin maintain a fresh and non-greasy state by regulating the skin oil balance, thereby preventing the occurrence of skin problems such as acne and blackheads. For people with oily skin, oil-control skin care products are not only essential for daily skin care but also the key to improving skin health and skin quality.

[0003] Azelaic acid is a natural organic acid with multiple functions such as oil control, bacteriostasis, anti-inflammation, and whitening. It can effectively regulate the activities of sebaceous glands, reduce the secretion amount of sebum, and keep the skin fresh and non-greasy. At the same time, azelaic acid also has a certain antibacterial and anti-inflammatory effect, which can reduce the number of harmful bacteria such as Propionibacterium acnes on the skin surface, effectively reduce the formation of acne, papules, and pustules, and inhibit the excessive secretion of sebaceous glands and reduce skin inflammatory reactions, thereby alleviating acne problems. In addition, azelaic acid can ensure the water-oil balance state of the skin by balancing the function of sebaceous glands and maintaining an appropriate oil secretion level of the skin.

[0004] In the prior art, azelaic acid has a certain irritating effect on the skin, eyes, mucous membranes, and upper respiratory tract, and is prone to causing skin discomfort, such as a burning sensation, itching, and stinging. In addition, since azelaic acid is insoluble in cold water and is a solid, it is difficult to be compatible with other oils, resulting in poor transdermal absorption ability of azelaic acid. Therefore, azelaic acid oil-control skin care products often have a relatively rough texture, are difficult to be evenly applied on the skin, and are prone to a granular or abrasive feeling, which not only affects the use experience of the product but also may increase the risk of skin friction and irritation. Summary of the Invention

[0005] In order to solve the problems mentioned in the above background art, the present invention provides the preparation and application of a cyclodextrin-encapsulated azelaic acid oil-control skin care product.

[0006] To achieve the above object, the present invention adopts the following technical scheme: The preparation of a cyclodextrin-encapsulated azelaic acid oil-control skin care product includes the following steps: S1. Add deionized water into a mixer, add cyclodextrin-azelaic acid clathrate, niacinamide, and allantoin, heat for the first time and continuously stir for 20 - 30 min to ensure that all components are fully dissolved and uniformly mixed to obtain an aqueous phase. Add glycerol, caprylic / capric triglyceride, polydimethylsiloxane, polysorbate-80, and tocopheryl acetate into the mixer and mix them. Heat the solution for the second time and continuously stir for 20 - 30 min to ensure that all components are fully dissolved and uniformly mixed to obtain an oil phase. Slowly add the oil phase into the aqueous phase and shear emulsify for 5 - 10 min to obtain a nanoemulsion; S2. Cool the nanoemulsion to 40 - 45 °C, add carbomer while stirring, continue to cool to room temperature, sequentially add phenoxyethanol, ferulic acid, menthol, and essence, stir evenly, adjust the pH value of the emulsion with triethanolamine, homogenize the emulsion with a homogenizer for 1 - 2 min, defoam with a vacuum defoaming device, and fill it after disinfection.

[0007] Further, the cyclodextrin-azelaic acid clathrate is prepared through the following steps: A1. Add polyoxyethylene diamine into N-methylpyrrolidone, stir until completely dissolved, add polyglutamic acid powder, add N,N'-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole, stir and react at room temperature for 24 - 48 h. After the reaction ends, perform vacuum distillation to obtain a copolymer solution; A2. Add HP-β-CD into N-methylpyrrolidone, stir for 20 - 30 min to obtain a cyclodextrin solution. Slowly drip the cyclodextrin solution into the copolymer solution, add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide, control the reaction temperature at 60 - 70 °C, continuously stir and react for 6 - 12 h. After the reaction ends, perform vacuum distillation to obtain a modified cyclodextrin solution; A3. Add azelaic acid into ethanol, stir until completely dissolved to obtain an azelaic acid ethanol solution. Slowly drip the azelaic acid ethanol solution into the modified cyclodextrin solution, heat to 80 - 90 °C, stir and react for 2 - 3 h. After the reaction ends, pour the reaction solution into cold water for precipitation, filter, collect the filter cake, wash it, and dry it to constant weight to obtain the cyclodextrin-azelaic acid clathrate.

[0008] Further, the mass ratio of deionized water, cyclodextrin-azelaic acid clathrate, niacinamide, allantoin, glycerol, caprylic / capric triglyceride, polydimethylsiloxane, polysorbate-80, and tocopheryl acetate in step S1 is (80 - 90):(2 - 3):(0.2 - 0.6):(0.1 - 0.2):(5 - 6):(3 - 4):(0.01 - 0.02):(0.01 - 0.1):(0.03 - 0.05).

[0009] Further, the mass ratio of the nanoemulsion, carbomer, phenoxyethanol, ferulic acid, menthol and essence in step S2 is 2:(0.2 - 0.3):(0.05 - 0.1):(0.01 - 0.03):(0.1 - 0.2):(0.01 - 0.1).

[0010] Further, in step S1, the temperature of the first heating is 50 - 60°C, the temperature of the second heating is 70 - 80°C, and the speed of shear emulsification is 2000 - 3000 rpm.

[0011] Further, in step S2, the adjusted pH value is 5.5 - 6.0, the rotation speed of the homogenizer is 8000 - 10000 rpm, and the homogenization pressure is 20 - 30 MPa.

[0012] Further, in step A1, the mass ratio of polyoxyethylene diamine, N-methylpyrrolidone, polyglutamic acid, N,N'-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole is (2 - 3):20:(1.5 - 2):(0.1 - 0.2):(0.05 - 0.08).

[0013] Further, in step A2, the mass ratio of HP-β-CD and N-methylpyrrolidone is (1 - 2):(10 - 15), and the mass ratio of the cyclodextrin solution, copolymer solution, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide is (10 - 12):(6 - 7):(0.5 - 0.6):(0.3 - 0.5).

[0014] Further, in step A3, the mass ratio of azelaic acid and ethanol is (2 - 3.5):(10 - 18), and the mass ratio of the azelaic acid ethanol solution and the modified cyclodextrin solution is (5 - 7):(15 - 20).

[0015] Further, add β-cyclodextrin powder to deionized water, heat to 50 - 60°C, stir until β-cyclodextrin is completely dissolved to form a transparent solution, slowly add a 10 - 15% sodium hydroxide solution by mass until the pH value of the solution is 10 - 11, transfer the reaction solution to an ice bath, control the temperature at 0 - 5°C, add propylene oxide dropwise at a dropping rate of 1 - 1.5 mL / min. After the dropping is completed, stir and react in the ice bath for 2 - 3 h. After the reaction is completed, add a 36 - 38% concentrated hydrochloric acid by mass to neutralize the pH value to 7, perform vacuum distillation to obtain a crude product, dissolve the crude product in ethanol, heat to gentle boiling, stir to precipitate impurities, filter to remove the impurities, and obtain HP-β-CD.

[0016] Among them, the dosage ratio of β-cyclodextrin powder, deionized water and propylene oxide is (5 - 6) g:50 mL:(2 - 3) mL.

[0017] According to another aspect of the present invention, there is provided an application of the preparation method of the above-mentioned cyclodextrin-encapsulated azelaic acid oil-control skin care product in the preparation of cosmetics or daily chemical products.

[0018] Advantages of the present invention: 1. In the technical solution of the present invention, the cyclodextrin-azelaic acid inclusion complex microscopically presents a unique molecular capsule structure. This structure is composed of the host molecule of modified cyclodextrin (HP-β-CD) and the guest molecule of azelaic acid through non-covalent interactions. The modified cyclodextrin molecule has a hydrophobic inner cavity and multiple hydrophilic hydroxypropyl side chains, enabling it to selectively encapsulate hydrophobic molecules. During the encapsulation process, azelaic acid molecules gradually enter the cavity of the modified cyclodextrin. Its hydrophobic part forms hydrophobic interactions with the cavity of the cyclodextrin, while the hydrophilic part forms hydrogen bonds or ion pairs with the hydrophilic side chains of the cyclodextrin or the external aqueous environment. This structure improves the water solubility of azelaic acid through the hydrophilic side chains of cyclodextrin, enabling azelaic acid to be better dispersed and dissolved in aqueous solutions, facilitating the uniform distribution of azelaic acid in skin care products, and thus being more easily absorbed and utilized by the skin.

[0019] 2. In the technical solution of the present invention, the inclusion complex structure provides physical protection for azelaic acid molecules, reducing their direct contact with the external environment, thereby reducing the possibility of chemical reactions such as photolysis, pyrolysis, and oxidation, contributing to the extension of the shelf life of skin care products and improving the use effect of the products. In addition, the encapsulation effect of cyclodextrin can mask certain irritating groups of azelaic acid molecules, reducing their direct irritation to the skin, making azelaic acid more suitable for skin care products for sensitive skin, and broadening its application scope. The inclusion complex structure can also serve as a controlled release system, controlling the release rate of azelaic acid by adjusting the interaction force between cyclodextrin and azelaic acid, contributing to the realization of the continuous action effect of skin care products and improving the user experience.

[0020] 3. The present invention adopts nanoemulsion technology to uniformly mix the oil phase and the water phase through shear emulsification to prepare a skin care product with a delicate texture and easy absorption. The nanoemulsion has a small particle size, can penetrate the skin more deeply, and provides long-lasting oil control and moisturizing effects. At the same time, by adjusting the proportion of ingredients in the formula, the skin feel of the product can be further optimized to make it more comfortable and non-greasy. Specific embodiments

[0021] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the scope of protection of the present invention.

[0022] Unless otherwise specified, the raw materials used in the present invention are all conventional products purchased from the market.

[0023] Preparation Example 1 Add 50 g of β-cyclodextrin powder to 500 mL of deionized water, heat to 50 °C, stir until β-cyclodextrin is completely dissolved to form a transparent solution, slowly add a 10% sodium hydroxide solution by mass until the pH value of the solution is 10, transfer the reaction solution to an ice bath, control the temperature at 0 °C, add 20 mL of propylene oxide dropwise at a dropping rate of 1 mL / min. After the addition is complete, stir and react in the ice bath for 2 h. After the reaction is completed, add a 36% concentrated hydrochloric acid by mass to neutralize the pH value to 7, and perform vacuum distillation to obtain a crude product. Dissolve the crude product in ethanol, heat to slightly boiling, stir to precipitate impurities, filter to remove impurities, and obtain HP-β-CD.

[0024] The cyclodextrin-azelaic acid inclusion complex is prepared by the following steps: A1. Add 20 g of polyethylene glycol diamine to 200 g of N-methylpyrrolidone, stir until completely dissolved, add 15 g of polyglutamic acid powder, add 1 g of N,N'-dicyclohexylcarbodiimide and 0.5 g of 1-hydroxybenzotriazole, stir and react at room temperature for 24 h. After the reaction is completed, perform vacuum distillation to obtain a copolymer solution.

[0025] A2. Add 10 g of HP-β-CD to 100 g of N-methylpyrrolidone, stir for 20 min to obtain a cyclodextrin solution. Slowly add 100 g of the cyclodextrin solution to 60 g of the copolymer solution, add 5 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 3 g of N-hydroxysuccinimide, control the reaction temperature at 60 °C, and continuously stir and react for 6 h. After the reaction is completed, perform vacuum distillation to obtain a modified cyclodextrin solution; A3. Add 20 g of azelaic acid to 100 g of ethanol, stir until completely dissolved to obtain an azelaic acid ethanol solution. Slowly add 50 g of the azelaic acid ethanol solution to 150 g of the modified cyclodextrin solution, heat to 80 °C, stir and react for 2 h. After the reaction is completed, pour the reaction solution into cold water to precipitate, filter, collect the filter cake, wash, and dry to constant weight to obtain the cyclodextrin-azelaic acid inclusion complex.

[0026] Preparation Example 2 Add 55 g of β-cyclodextrin powder to 500 mL of deionized water, heat to 55 °C, stir until the β-cyclodextrin is completely dissolved to form a transparent solution, slowly add a 13% sodium hydroxide solution until the pH of the solution reaches 10.5, transfer the reaction solution to an ice bath, control the temperature at 2 °C, add 25 mL of propylene oxide dropwise at a dropping rate of 1.3 mL / min. After the addition is complete, stir and react in the ice bath for 2.5 h. After the reaction is completed, add 37% concentrated hydrochloric acid dropwise to neutralize the pH to 7, and perform vacuum distillation to obtain the crude product. Dissolve the crude product in ethanol, heat to slightly boiling, stir to precipitate impurities, filter to remove impurities, and obtain HP-β-CD.

[0027] The cyclodextrin-azelaic acid inclusion complex is prepared by the following steps: A1. Add 25 g of polyethylene oxide diamine to 200 g of N-methylpyrrolidone, stir until completely dissolved, add 18 g of polyglutamic acid powder, add 1.5 g of N,N'-dicyclohexylcarbodiimide and 0.7 g of 1-hydroxybenzotriazole, stir and react at room temperature for 36 h. After the reaction is completed, perform vacuum distillation to obtain the copolymer solution.

[0028] A2. Add 15 g of HP-β-CD to 125 g of N-methylpyrrolidone, stir for 25 min to obtain the cyclodextrin solution. Slowly add 110 g of the cyclodextrin solution to 65 g of the copolymer solution, add 5.5 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 4 g of N-hydroxysuccinimide, control the reaction temperature at 65 °C, and continuously stir and react for 8 h. After the reaction is completed, perform vacuum distillation to obtain the modified cyclodextrin solution; A3. Add 30 g of azelaic acid to 150 g of ethanol, stir until completely dissolved to obtain the azelaic acid ethanol solution. Slowly add 60 g of the azelaic acid ethanol solution to 180 g of the modified cyclodextrin solution, heat to 85 °C, stir and react for 2.5 h. After the reaction is completed, pour the reaction solution into cold water to precipitate, filter, collect the filter cake, wash, and dry to constant weight to obtain the cyclodextrin-azelaic acid inclusion complex.

[0029] Preparation Example 3 Add 60 g of β-cyclodextrin powder to 500 mL of deionized water, heat to 60 °C, stir until the β-cyclodextrin is completely dissolved to form a transparent solution, slowly add a 15% sodium hydroxide solution until the pH of the solution reaches 11, transfer the reaction solution to an ice bath, control the temperature at 5 °C, add 30 mL of propylene oxide dropwise at a dropping rate of 1.5 mL / min. After the addition is complete, stir and react in the ice bath for 3 h. After the reaction is completed, add 38% concentrated hydrochloric acid dropwise to neutralize the pH to 7, and perform vacuum distillation to obtain the crude product. Dissolve the crude product in ethanol, heat to slightly boiling, stir to precipitate impurities, filter to remove impurities, and obtain HP-β-CD.

[0030] The cyclodextrin-azelaic acid inclusion compound is prepared by the following steps: A1. Add 30 g of polyethylene oxide diamine to 200 g of N-methylpyrrolidone, stir until completely dissolved, add 20 g of polyglutamic acid powder, add 2 g of N,N'-dicyclohexylcarbodiimide and 0.8 g of 1-hydroxybenzotriazole, stir and react at room temperature for 48 h. After the reaction is completed, carry out vacuum distillation to obtain a copolymer solution.

[0031] A2. Add 20 g of HP-β-CD to 150 g of N-methylpyrrolidone, stir for 30 min to obtain a cyclodextrin solution. Slowly drop 120 g of the cyclodextrin solution into 70 g of the copolymer solution, add 6 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 5 g of N-hydroxysuccinimide, control the reaction temperature at 70 °C, continuously stir and react for 12 h. After the reaction is completed, carry out vacuum distillation to obtain a modified cyclodextrin solution; A3. Add 35 g of azelaic acid to 180 g of ethanol, stir until completely dissolved to obtain an azelaic acid ethanol solution. Slowly drop 70 g of the azelaic acid ethanol solution into 200 g of the modified cyclodextrin solution, heat to 90 °C, stir and react for 3 h. After the reaction is completed, pour the reaction solution into cold water for precipitation, filter, collect the filter cake, wash, and dry to constant weight to obtain the cyclodextrin-azelaic acid inclusion compound.

[0032] Example 1 The preparation of a cyclodextrin-encapsulated azelaic acid oil-control skin care product includes the following steps: S1. Add 800 g of deionized water to a mixer, add 20 g of the cyclodextrin-azelaic acid inclusion compound prepared in Preparation Example 1, 2 g of niacinamide, and 1 g of allantoin, heat to 50 °C for the first time and continuously stir for 20 min to obtain an aqueous phase. Add 50 g of glycerol, 30 g of caprylic / capric triglyceride, 0.1 g of polydimethylsiloxane, 0.1 g of polysorbate-80, and 0.3 g of tocopheryl acetate to the mixer for mixing. Heat the solution to 70 °C for the second time and continuously stir for 20 min to obtain an oil phase. Slowly add the oil phase to the aqueous phase and shear and emulsify at a speed of 2000 rpm for 5 min to obtain a nanoemulsion; S2. Cool 20 g of the nanoemulsion to 40 °C, add 2 g of carbomer while stirring, continue to cool to room temperature, sequentially add 0.5 g of phenoxyethanol, 0.1 g of ferulic acid, 0.1 g of menthol, and 0.1 g of essence, stir evenly, adjust the pH value of the emulsion to 5.5 with triethanolamine, homogenize the emulsion with a homogenizer for 1 min, the rotation speed of the homogenizer is 8000 rpm, the homogenization pressure is 20 MPa, carry out defoaming with a vacuum defoaming device, and fill after disinfection.

[0033] Example 2 Preparation of a cyclodextrin - encapsulated azelaic acid oil - controlling skin care product, comprising the following steps: S1. Add 850 g of deionized water into a mixer, add 25 g of the cyclodextrin - azelaic acid clathrate prepared in Preparation Example 2, 4 g of niacinamide, and 1.5 g of allantoin, mix them, heat to 55 °C for the first time and continuously stir for 25 min to obtain an aqueous phase. Add 55 g of glycerol, 35 g of caprylic / capric triglyceride, 0.15 g of polydimethylsiloxane, 0.3 g of polysorbate - 80, and 0.4 g of tocopheryl acetate into the mixer and mix. Heat the solution to 75 °C for the second time and continuously stir for 25 min to obtain an oil phase. Slowly add the oil phase into the aqueous phase and shear - emulsify at a speed of 2500 rpm for 8 min to obtain a nano - emulsion; S2. Cool 20 g of the nano - emulsion to 42 °C, add 2.5 g of carbomer while stirring, continue to cool to room temperature, successively add 0.7 g of phenoxyethanol, 0.2 g of ferulic acid, 0.15 g of menthol, and 0.7 g of essence, stir evenly, adjust the pH value of the emulsion to 5.8 with triethanolamine, homogenize the emulsion with a homogenizer for 1.5 min, the rotation speed of the homogenizer is 9000 rpm, the homogenization pressure is 25 MPa, defoam with a vacuum defoaming device, and fill after disinfection.

[0034] Example 3 Preparation of a cyclodextrin - encapsulated azelaic acid oil - controlling skin care product, comprising the following steps: S1. Add 900 g of deionized water into a mixer, add 30 g of the cyclodextrin - azelaic acid clathrate prepared in Preparation Example 3, 6 g of niacinamide, and 2 g of allantoin, mix them, heat to 60 °C for the first time and continuously stir for 30 min to obtain an aqueous phase. Add 60 g of glycerol, 40 g of caprylic / capric triglyceride, 0.2 g of polydimethylsiloxane, 1 g of polysorbate - 80, and 0.5 g of tocopheryl acetate into the mixer and mix. Heat the solution to 80 °C for the second time and continuously stir for 30 min to obtain an oil phase. Slowly add the oil phase into the aqueous phase and shear - emulsify at a speed of 3000 rpm for 10 min to obtain a nano - emulsion; S2. Cool 20 g of the nano - emulsion to 45 °C, add 3 g of carbomer while stirring, continue to cool to room temperature, successively add 1 g of phenoxyethanol, 0.3 g of ferulic acid, 0.2 g of menthol, and 1 g of essence, stir evenly, adjust the pH value of the emulsion to 6.0 with triethanolamine, homogenize the emulsion with a homogenizer for 2 min, the rotation speed of the homogenizer is 10000 rpm, the homogenization pressure is 30 MPa, defoam with a vacuum defoaming device, and fill after disinfection.

[0035] Comparative Example 1 The difference between this comparative example and Example 1 is that the cyclodextrin - azelaic acid clathrate is not added, and the remaining steps are the same as those in Example 1.

[0036] Comparative Example 2 The difference between this comparative example and Example 2 is that azelaic acid is used instead of cyclodextrin-azelaic acid inclusion complex, and the remaining steps are the same as those in Example 2.

[0037] Comparative Example 3 The difference between this comparative example and Example 3 is that HP-β-CD in Preparation Example 3 is used instead of cyclodextrin-azelaic acid inclusion complex, and the remaining steps are the same as those in Example 3.

[0038] (I) In vitro sustained-release performance test: Take 1 g of the emulsion samples of Examples 1-3 and Comparative Examples 2-3 respectively, put them into a dialysis bag with a molecular weight cut-off of 3500 Da, immerse them in 200 mL of phosphate buffer solution with pH = 5.5 (simulating the pH of the skin surface), oscillate in a constant temperature water bath at 37 °C at a speed of 100 rpm, and sample 1 mL at 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h, and 24 h (while supplementing an equal amount of fresh buffer solution), and measure the azelaic acid concentration by HPLC (chromatographic conditions: C18 column, mobile phase methanol: 0.1% phosphoric acid = 70:30, detection wavelength 210 nm). The results are shown in Table 1: Table 1. Results of in vitro sustained-release performance test of Examples 1-3 and Comparative Examples 2-3

[0039] (II) Oil control effect test: Recruit 60 volunteers with oily skin (half male and half female, aged 18-35 years old), randomly divide them into 6 groups, corresponding to Examples 1-3 groups and Comparative Examples 1-3 groups respectively. After cleaning the face, sit still for 30 min (temperature 25 ± 1 °C, humidity 50 ± 5%), use a Sebumeter to measure the initial sebum amount (μg / cm²) in the T area of the forehead, apply 0.5 g of the corresponding sample once, measure the change in sebum amount at 2 h, 4 h, 6 h, and 8 h respectively, take the average value, and calculate the sebum inhibition rate = (initial value - test value) / initial value × 100%. The results are shown in Table 2: Table 2. Sebum inhibition rate results of Examples 1-3 and Comparative Examples 1-3 (%)

[0040] (III) Stability accelerated test: Divide the emulsions prepared in Examples 1-3 and Comparative Examples 1-3 into 3 portions and sub-pack them into 18 transparent glass bottles, and set 3 groups of storage conditions: ① 4 °C refrigeration (control group); ② 25 °C / 60% RH (conventional storage); ③ 40 °C / 75% RH (accelerated test). After 6 months, sample and detect the azelaic acid content (HPLC) of each emulsion, and observe the appearance state (color, layering situation). The results are shown in Table 3: Table 3. Results of stability accelerated test of Examples 1-3 and Comparative Examples 1-3

[0041] (IV)Skin irritation test: 20 μL of each sample of Examples 1-3 and Comparative Examples 1-3 was applied to the flexor side of the forearms of 60 volunteers using a Finn Chamber patch tester, and the patch was applied for 48 h under occlusion. After removal, the erythema / edema scores (0 points: no erythema / edema; 1 point: slight erythema; 2 points: obvious erythema, mild edema; 3 points: moderate erythema, moderate edema; 4 points: severe erythema, severe edema) were observed at 0.5 h and 24 h, the TEWL value (transepidermal water loss) was recorded, and the average value was calculated after statistical data; 50 μL of 5% lactic acid solution was applied to the flexor side of the forearm for the lactic acid sting test. The subjective symptoms of the subjects were asked at 2.5 min and 5 min. The scoring criteria were: grade 0: no stinging sensation, grade 1: mild stinging, grade 2: moderate stinging, grade 3: severe stinging. The results are shown in Tables 4 and 5: Table 4. Results of skin irritation test of Examples 1-3 and Comparative Examples 1-3

[0042] Table 5. Results of lactic acid sting test of Examples 1-3 and Comparative Examples 1-3

[0043] As can be seen from Table 1, for Examples 1-3: the azelaic acid release concentration within 24 hours gradually increased, indicating that the cyclodextrin-azelaic acid inclusion complex may have good sustained-release performance. In Comparative Example 2, azelaic acid was not included by cyclodextrin, the release rate was fast, and a high concentration was reached in a short time, lacking the sustained-release effect. In Comparative Example 3, only HP-β-CD was used, and the sustained-release effect of azelaic acid was between that of the example and Comparative Example 2, indicating that pure HP-β-CD has a certain sustained-release effect, but it is not as significant as that of the cyclodextrin-azelaic acid inclusion complex.

[0044] As can be seen from Table 2, the sebum inhibition rates of Examples 1-3 increased significantly with time, indicating that the cyclodextrin-azelaic acid inclusion complex may have good oil control effect. In Comparative Example 1, there was no azelaic acid, and the oil control effect was the worst. In Comparative Example 2, azelaic acid was not included, and the oil control effect was inferior to that of the example. It may be because azelaic acid directly acts on the skin, with greater irritation, affecting the persistence of the oil control effect. The oil control effect of Comparative Example 3 was between that of the example and Comparative Example 2, indicating that HP-β-CD has a certain synergistic effect on azelaic acid, but it is not as significant as that of the inclusion complex.

[0045] As can be seen from Table 3, under the conditions of 4 °C, 25 °C / 60% RH, and 40 °C / 75% RH, the azelaic acid content of Examples 1-3 remained high, and the appearance state changed slightly, indicating that the cyclodextrin-azelaic acid inclusion complex has good stability. In Comparative Example 2, the azelaic acid content decreased significantly, and the appearance state changed significantly. In Comparative Example 3, the degree of decrease in azelaic acid content was between that of the example and Comparative Example 2.

[0046] As can be seen from Table 4, the erythema / edema scores and TEWL values of Examples 1-3 were lower, indicating that the cyclodextrin-azelaic acid inclusion compound had little irritation to the skin. The erythema / edema scores and TEWL values of Comparative Examples 1-3 were higher, indicating greater irritation.

[0047] As can be seen from Table 5, there was no stinging sensation in Examples 1-3, indicating that the cyclodextrin-azelaic acid inclusion compound was mild to the skin. There was no stinging sensation in Comparative Example 1, indicating that when there was no azelaic acid, other components had no significant irritation to the skin. Comparative Example 2 had moderate stinging, indicating that azelaic acid directly acting on the skin without inclusion had greater irritation. Comparative Example 3 had mild stinging, indicating that HP-β-CD had a certain effect of reducing the stinging of azelaic acid. In the skin irritation test and lactic acid stinging test, the cyclodextrin-azelaic acid inclusion compound reduced the direct irritation of azelaic acid to the skin by slowly releasing azelaic acid, and improved the mildness of the product.

[0048] In summary, by adding the cyclodextrin-azelaic acid inclusion compound prepared by the Preparation Examples, the products of Examples 1-3 had a certain oil control effect, and at the same time achieved the effects of slow release, stability and stinging reduction of azelaic acid, improving the performance and safety of the skin care products.

[0049] In the description of the specification, the descriptions referring to terms such as "Preparation Example", "Example", "each example", etc. mean that the specific features, structures, materials or characteristics described in connection with that example or preparation example are included in at least one example or preparation example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same example or preparation example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more examples or preparation examples in a suitable manner.

[0050] The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution and inventive concept of the present invention, makes equivalent substitutions or changes, and all should be covered by the protection scope of the present invention.

Claims

1. A preparation method of a cyclodextrin-wrapped azelaic acid oil-control skin care product, characterized in that, It includes the following steps: S1. Add deionized water into a mixer, add cyclodextrin-azelaic acid inclusion compound, niacinamide, and allantoin, mix them, heat and stir for 20 - 30 min for the first time to obtain an aqueous phase. Mix glycerol, caprylic / capric triglyceride, polydimethylsiloxane, polysorbate-80, and tocopheryl acetate, heat and stir for 20 - 30 min for the second time to obtain an oil phase. Slowly add the oil phase into the aqueous phase and perform shear emulsification for 5 - 10 min to obtain a nanoemulsion. S2. Cool the nanoemulsion to 40 - 45 °C, add carbomer while stirring, continue to cool to room temperature, sequentially add phenoxyethanol, ferulic acid, menthol, and essence, adjust the pH value of the emulsion with triethanolamine, homogenize with a homogenizer for 1 - 2 min, defoam, and fill into containers after disinfection.

2. The preparation method of a cyclodextrin-encapsulated azelaic acid oil-control skin care product according to claim 1, characterized in that, The cyclodextrin-azelaic acid inclusion compound is prepared through the following steps: A1. Add polyoxyethylene diamine into N-methylpyrrolidone, stir to dissolve, add polyglutamic acid powder, add N,N'-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole, stir and react at room temperature for 24 - 48 h. After the reaction ends, perform vacuum distillation to obtain a copolymer solution. A2. Add HP-β-CD into N-methylpyrrolidone, stir for 20 - 30 min to obtain a cyclodextrin solution. Slowly drip the cyclodextrin solution into the copolymer solution, add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide, control the reaction temperature at 60 - 70 °C, continuously stir and react for 6 - 12 h. After the reaction ends, perform vacuum distillation to obtain a modified cyclodextrin solution. A3. Add azelaic acid into ethanol, stir to dissolve to obtain an azelaic acid ethanol solution. Slowly drip the azelaic acid ethanol solution into the modified cyclodextrin solution, heat to 80 - 90 °C, stir and react for 2 - 3 h. After the reaction ends, pour the reaction solution into cold water for precipitation, filter, collect the filter cake, wash, and dry to constant weight to obtain the cyclodextrin-azelaic acid inclusion compound.

3. The preparation method of a cyclodextrin-encapsulated azelaic acid oil-control skin care product according to claim 1, characterized in that, In step S1, the mass ratio of deionized water, cyclodextrin-azelaic acid inclusion compound, niacinamide, allantoin, glycerol, caprylic / capric triglyceride, polydimethylsiloxane, polysorbate-80, and tocopheryl acetate is (80 - 90):(2 - 3):(0.2 - 0.6):(0.1 - 0.2):(5 - 6):(3 - 4):(0.01 - 0.02):(0.01 - 0.1):(0.03 - 0.05).

4. The preparation method of a cyclodextrin-encapsulated azelaic acid oil-control skin care product according to claim 1, characterized in that, In step S2, the mass ratio of the nanoemulsion, carbomer, phenoxyethanol, ferulic acid, menthol, and essence is 2:(0.2 - 0.3):(0.05 - 0.1):(0.01 - 0.03):(0.1 - 0.2):(0.01 - 0.1).

5. The preparation method of a cyclodextrin-encapsulated azelaic acid oil-control skin care product according to claim 1, characterized in that, In step S1, the temperature of the first heating is 50 - 60 °C, the temperature of the second heating is 70 - 80 °C, and the speed of shear emulsification is 2000 - 3000 rpm.

6. The preparation method of a cyclodextrin-encapsulated azelaic acid oil-control skin care product according to claim 1, characterized in that, In step S2, the adjusted pH value is 5.5 - 6.0, the rotation speed of the homogenizer is 8000 - 10000 rpm, and the homogenization pressure is 20 - 30 MPa.

7. The preparation method of a cyclodextrin-encapsulated azelaic acid oil-control skin care product according to claim 2, characterized in that, In step A1, the mass ratio of polyoxyethylene diamine, N-methylpyrrolidone, polyglutamic acid, N,N'-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole is (2-3):20:(1.5-2):(0.1-0.2):(0.05-0.08).

8. The preparation method of a cyclodextrin-encapsulated azelaic acid oil-control skin care product according to claim 2, characterized in that, In step A2, the mass ratio of HP-β-CD and N-methylpyrrolidone is (1-2):(10-15), and the mass ratio of cyclodextrin solution, copolymer solution, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide is (10-12):(6-7):(0.5-0.6):(0.3-0.5).

9. The preparation method of a cyclodextrin-encapsulated azelaic acid oil-control skin care product according to claim 2, characterized in that, In step A3, the mass ratio of azelaic acid and ethanol is (2-3.5):(10-18), and the mass ratio of azelaic acid ethanol solution and modified cyclodextrin solution is (5-7):(15-20).

10. Use of the method for preparing a cyclodextrin-encapsulated azelaic acid oil-control skin care product according to any one of claims 1-9 in the preparation of cosmetics or daily chemical products.

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