Preparation and application of a cyclodextrin-encapsulated azelaic acid oil-controlling skincare product

Abstract

This invention relates to the field of cosmetic technology, and more particularly to the preparation and application of a cyclodextrin-encapsulated azelaic acid oil-controlling skincare product. The process includes the following steps: S1, adding deionized water to a mixer, adding the cyclodextrin-azelaic acid inclusion complex, niacinamide, and allantoin, and mixing to obtain an aqueous phase; mixing glycerin, caprylic / capric triglycerides, polydimethylsiloxane, polysorbate-80, and tocopheryl acetate to obtain an oil phase; slowly adding the oil phase to the aqueous phase, shearing and emulsifying to obtain a nanoemulsion; S2, cooling the nanoemulsion, adding carbomer while stirring, continuing to cool to room temperature, then sequentially adding phenoxyethanol, ferulic acid, menthol, and fragrance; adjusting the pH of the emulsion with triethanolamine, homogenizing, defoaming, sterilizing, and filling. This invention, by adjusting the proportions of ingredients in the formula, can further optimize the skin feel of the product, making it more comfortable, non-greasy, and providing a long-lasting oil-controlling effect.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, and in particular to the preparation and application of a cyclodextrin-encapsulated azelaic acid oil-controlling skin care product. Background Technology

[0002] Oily skin, due to its overactive sebaceous glands, is prone to clogged pores, frequent acne breakouts, and excessive oiliness, causing numerous inconveniences and problems. Oil-control skincare products are those that effectively reduce sebum secretion and improve oily skin. These products help maintain a clean, non-greasy state by regulating the skin's oil balance, thus preventing acne, blackheads, and other skin issues. For people with oily skin, oil-control skincare products are not only essential for daily skincare but also key to improving skin health and texture.

[0003] Azelaic acid is a natural organic acid with multiple benefits, including oil control, antibacterial properties, anti-inflammatory effects, and skin whitening. It effectively regulates sebaceous gland activity, reducing sebum secretion and keeping skin fresh and non-greasy. Simultaneously, azelaic acid possesses antibacterial and anti-inflammatory properties, reducing the number of harmful bacteria on the skin surface, such as Propionibacterium acnes, effectively reducing the formation of blackheads, papules, and pustules, inhibiting excessive sebum secretion, and alleviating skin inflammation, thereby alleviating acne problems. Furthermore, azelaic acid can balance sebaceous gland function, maintaining appropriate sebum secretion levels and ensuring the skin's water-oil balance.

[0004] In existing technologies, azelaic acid has a certain irritant effect on the skin, eyes, mucous membranes, and upper respiratory tract, easily causing skin discomfort such as burning, itching, and stinging sensations. Furthermore, because azelaic acid is insoluble in cold water and, as a solid, is difficult to integrate with other oils, its transdermal absorption capacity is poor. Therefore, azelaic acid oil-controlling skincare products often have a rough texture, making them difficult to apply evenly to the skin and prone to producing a grainy or abrasive feel. This not only affects the user experience but may also increase the risk of skin friction and irritation. Summary of the Invention

[0005] To address the problems mentioned in the background section, this invention provides a preparation and application of a cyclodextrin-encapsulated azelaic acid oil-controlling skincare product.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] The preparation of an oil-controlling skincare product encapsulated in cyclodextrin and azelaic acid includes the following steps:

[0008] S1. Add deionized water to a mixer, add cyclodextrin-azeliaic acid inclusion complex, nicotinamide, and allantoin, mix, heat for the first time and stir continuously for 20-30 minutes to ensure that all components are fully dissolved and uniformly mixed to obtain the aqueous phase. Add glycerol, caprylic / capric triglyceride, polydimethylsiloxane, polysorbate-80, and tocopheryl acetate to the mixer and mix. Heat the solution for the second time and stir continuously for 20-30 minutes to ensure that all components are fully dissolved and uniformly mixed to obtain the oil phase. Slowly add the oil phase to the aqueous phase and shear emulsify for 5-10 minutes to obtain the nanoemulsion.

[0009] S2. Cool the nanoemulsion to 40-45℃, add carbomer while stirring, continue cooling to room temperature, add phenoxyethanol, ferulic acid, menthol and fragrance in sequence, stir evenly, adjust the pH of the emulsion with triethanolamine, homogenize the emulsion with a homogenizer for 1-2 minutes, defoam with a vacuum defoaming device, sterilize and then fill.

[0010] Furthermore, the cyclodextrin-azeliaic acid inclusion complex is prepared by the following steps:

[0011] A1. Add polyoxyethylene diamine to N-methylpyrrolidone and stir until completely dissolved. Add polyglutamic acid powder, N,N'-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole. Stir and react at room temperature for 24-48 hours. After the reaction is completed, distill under reduced pressure to obtain the copolymer solution.

[0012] A2. Add HP-β-CD to N-methylpyrrolidone and stir for 20-30 min to obtain a cyclodextrin solution. Slowly add the cyclodextrin solution dropwise to the copolymer solution, add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide, control the reaction temperature at 60-70℃, and continue stirring for 6-12 h. After the reaction is completed, distill under reduced pressure to obtain the modified cyclodextrin solution.

[0013] A3. Add azelaic acid to ethanol and stir until completely dissolved to obtain an azelaic acid ethanol solution. Slowly add the azelaic acid ethanol solution dropwise to the modified cyclodextrin solution, heat to 80-90℃, and stir for 2-3 hours. After the reaction is complete, 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.

[0014] Further, in step S1, the mass ratio of deionized water, cyclodextrin-azeliaic acid inclusion complex, nicotinamide, 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).

[0015] Further, in step S2, the mass ratio of nanoemulsion, carbomer, phenoxyethanol, ferulic acid, menthol and fragrance is 2: (0.2-0.3): (0.05-0.1): (0.01-0.03): (0.1-0.2): (0.01-0.1).

[0016] Furthermore, in step S1, the temperature of the first heating is 50-60℃, the temperature of the second heating is 70-80℃, and the shear emulsification speed is 2000-3000 rpm.

[0017] Furthermore, in step S2, the pH value is adjusted to 5.5-6.0, the homogenizer speed is 8000-10000 rpm, and the homogenization pressure is 20-30 MPa.

[0018] 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).

[0019] Further, in step A2, the mass ratio of HP-β-CD to N-methylpyrrolidone is (1-2):(10-15), and the cyclodextrin solution, copolymer solution, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide are (10-12):(6-7):(0.5-0.6):(0.3-0.5).

[0020] Further, in step A3, the mass ratio of azelaic acid to ethanol is (2-3.5):(10-18), and the mass ratio of azelaic acid ethanol solution to modified cyclodextrin solution is (5-7):(15-20).

[0021] Further, β-cyclodextrin powder was added to deionized water and heated to 50-60℃. The mixture was stirred until the β-cyclodextrin was completely dissolved, forming a transparent solution. A 10-15% sodium hydroxide solution was slowly added dropwise until the pH of the solution was 10-11. The reaction solution was transferred to an ice bath and the temperature was controlled at 0-5℃. Propylene oxide was added dropwise at a rate of 1-1.5 mL / min. After the addition was complete, the reaction was stirred in an ice bath for 2-3 hours. After the reaction was completed, concentrated hydrochloric acid (36-38% by mass) was added dropwise to neutralize the pH to 7. The mixture was then distilled under reduced pressure to obtain the crude product. The crude product was dissolved in ethanol, heated to a gentle boil, and stirred to precipitate impurities. The impurities were removed by filtration to obtain HP-β-CD.

[0022] The ratio of β-cyclodextrin powder, deionized water and propylene oxide is (5-6) g: 50 mL: (2-3) mL.

[0023] According to another aspect of the present invention, the method for preparing the above-mentioned cyclodextrin-encapsulated azelaic acid oil-controlling skin care product is provided for use in the preparation of cosmetics or daily chemical products.

[0024] The beneficial effects of this invention are:

[0025] 1. In the technical solution of this invention, the cyclodextrin-azeliaic acid inclusion complex exhibits a unique molecular capsule structure at the microscopic level. This structure is formed by the host molecule of modified cyclodextrin (HP-β-CD) and the guest molecule of azeliaic acid through non-covalent interactions. The modified cyclodextrin molecule has a hydrophobic internal cavity and multiple hydrophilic hydroxypropyl side chains, enabling it to selectively include hydrophobic molecules. During the inclusion process, azeliaic acid molecules gradually enter the cavity of the modified cyclodextrin. Its hydrophobic portion forms a hydrophobic interaction with the cavity of the cyclodextrin, while its hydrophilic portion 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 azeliaic acid through the hydrophilic side chains of the cyclodextrin, allowing azeliaic acid to be better dispersed and dissolved in aqueous solutions, which helps the uniform distribution of azeliaic acid in skin care products, thus making it easier for the skin to absorb and utilize it.

[0026] 2. In the technical solution of this invention, the inclusion complex structure provides physical protection for azelaic acid molecules, reducing their direct contact with the external environment. This lowers the likelihood of chemical reactions such as photolysis, pyrolysis, and oxidation, helping to extend the shelf life of skincare products and improve their effectiveness. Furthermore, the inclusion effect of cyclodextrin can mask certain irritating groups of azelaic acid molecules, reducing direct skin irritation and making azelaic acid more suitable for use in skincare products for sensitive skin, thus broadening its application range. 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, helping to achieve sustained effects in skincare products and improving the user experience.

[0027] 3. This invention utilizes nanoemulsion technology to uniformly mix the oil and water phases through shear emulsification, producing a skincare product with a delicate texture and easy absorption. The small particle size of the nanoemulsion allows for deeper penetration into the skin, providing long-lasting oil control and moisturizing effects. Furthermore, by adjusting the proportions of ingredients in the formula, the product's feel can be further optimized, making it more comfortable and non-greasy. Detailed Implementation

[0028] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0029] Unless otherwise specified, the raw materials used in this invention are all from commercially available conventional products.

[0030] Preparation Example 1

[0031] Add 50g of β-cyclodextrin powder to 500mL of deionized water, heat to 50℃, and stir until the β-cyclodextrin is completely dissolved to form a transparent solution. Slowly add 10% sodium hydroxide solution until the pH of the solution is 10. Transfer the reaction solution to an ice bath and control the temperature at 0℃. Add 20mL of propylene oxide at a rate of 1mL / min. After the addition is complete, stir the reaction in an ice bath for 2 hours. After the reaction is complete, add 36% concentrated hydrochloric acid to neutralize the pH to 7. Distill under reduced pressure to obtain the crude product. Dissolve the crude product in ethanol, heat to a gentle boil, stir to precipitate impurities, filter to remove impurities, and obtain HP-β-CD.

[0032] The cyclodextrin-azeliaic acid inclusion complex is prepared by the following steps:

[0033] A1. Add 20g of polyoxyethylene diamine to 200g of N-methylpyrrolidone and stir until completely dissolved. Add 15g of polyglutamic acid powder, 1g of N,N'-dicyclohexylcarbodiimide and 0.5g of 1-hydroxybenzotriazole. Stir and react at room temperature for 24h. After the reaction is completed, distill under reduced pressure to obtain the copolymer solution.

[0034] A2. Add 10g HP-β-CD to 100g N-methylpyrrolidone and stir for 20min to obtain a cyclodextrin solution. Slowly add 100g of the cyclodextrin solution to 60g of the copolymer solution, add 5g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 3g of N-hydroxysuccinimide, control the reaction temperature at 60℃, and continue stirring for 6h. After the reaction is completed, distill under reduced pressure to obtain the modified cyclodextrin solution.

[0035] A3. Add 20g of azelaic acid to 100g of ethanol and stir until completely dissolved to obtain an azelaic acid ethanol solution. Slowly add 50g of the azelaic acid ethanol solution to 150g of modified cyclodextrin solution, heat to 80℃, and stir for 2 hours. After the reaction is complete, 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.

[0036] Preparation Example 2

[0037] Add 55g of β-cyclodextrin powder to 500mL of deionized water, heat to 55℃, and stir until the β-cyclodextrin is completely dissolved to form a transparent solution. Slowly add 13% sodium hydroxide solution until the pH of the solution is 10.5. Transfer the reaction solution to an ice bath and control the temperature at 2℃. Add 25mL of propylene oxide at a rate of 1.3mL / min. After the addition is complete, stir the reaction in an ice bath for 2.5h. After the reaction is complete, add 37% concentrated hydrochloric acid to neutralize the pH to 7. Distill under reduced pressure to obtain the crude product. Dissolve the crude product in ethanol, heat to a gentle boil, stir to precipitate impurities, filter to remove impurities, and obtain HP-β-CD.

[0038] The cyclodextrin-azeliaic acid inclusion complex is prepared by the following steps:

[0039] A1. Add 25g of polyoxyethylene diamine to 200g of N-methylpyrrolidone and stir until completely dissolved. Add 18g of polyglutamic acid powder, 1.5g of N,N'-dicyclohexylcarbodiimide and 0.7g of 1-hydroxybenzotriazole. Stir and react at room temperature for 36h. After the reaction is completed, distill under reduced pressure to obtain the copolymer solution.

[0040] A2. Add 15g HP-β-CD to 125g N-methylpyrrolidone and stir for 25min to obtain a cyclodextrin solution. Slowly add 110g of the cyclodextrin solution to 65g of the copolymer solution, add 5.5g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 4g of N-hydroxysuccinimide, control the reaction temperature at 65℃, and continue stirring for 8h. After the reaction is completed, distill under reduced pressure to obtain a modified cyclodextrin solution.

[0041] A3. Add 30g of azelaic acid to 150g of ethanol and stir until completely dissolved to obtain an azelaic acid ethanol solution. Slowly add 60g of the azelaic acid ethanol solution to 180g of modified cyclodextrin solution, heat to 85℃, and stir for 2.5h. After the reaction is complete, 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.

[0042] Preparation Example 3

[0043] Add 60g of β-cyclodextrin powder to 500mL of deionized water, heat to 60℃, and stir until the β-cyclodextrin is completely dissolved to form a transparent solution. Slowly add 15% sodium hydroxide solution until the pH of the solution is 11. Transfer the reaction solution to an ice bath and control the temperature at 5℃. Add 30mL of propylene oxide at a rate of 1.5mL / min. After the addition is complete, stir the reaction in an ice bath for 3 hours. After the reaction is complete, add 38% concentrated hydrochloric acid to neutralize the pH to 7. Distill under reduced pressure to obtain the crude product. Dissolve the crude product in ethanol, heat to a gentle boil, stir to precipitate impurities, filter to remove impurities, and obtain HP-β-CD.

[0044] The cyclodextrin-azeliaic acid inclusion complex is prepared by the following steps:

[0045] A1. Add 30g of polyoxyethylene diamine to 200g of N-methylpyrrolidone and stir until completely dissolved. Add 20g of polyglutamic acid powder, 2g of N,N'-dicyclohexylcarbodiimide and 0.8g of 1-hydroxybenzotriazole. Stir and react at room temperature for 48h. After the reaction is completed, distill under reduced pressure to obtain the copolymer solution.

[0046] A2. Add 20g HP-β-CD to 150g N-methylpyrrolidone and stir for 30min to obtain a cyclodextrin solution. Slowly add 120g of the cyclodextrin solution to 70g of the copolymer solution, add 6g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 5g of N-hydroxysuccinimide, control the reaction temperature at 70℃, and continue stirring for 12h. After the reaction is completed, distill under reduced pressure to obtain a modified cyclodextrin solution.

[0047] A3. Add 35g of azelaic acid to 180g of ethanol and stir until completely dissolved to obtain an azelaic acid ethanol solution. Slowly add 70g of the azelaic acid ethanol solution to 200g of modified cyclodextrin solution, heat to 90℃, and stir for 3h. After the reaction is complete, 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.

[0048] Example 1

[0049] The preparation of an oil-controlling skincare product encapsulated in cyclodextrin and azelaic acid includes the following steps:

[0050] S1. Add 800g of deionized water to a mixer, add 20g of the cyclodextrin-azeliaic acid inclusion complex prepared in Preparation Example 1, 2g of nicotinamide, and 1g of allantoin, and mix. Heat to 50°C for the first time and stir continuously for 20min to obtain an aqueous phase. Add 50g of glycerol, 30g of caprylic / capric triglyceride, 0.1g of polydimethylsiloxane, 0.1g of polysorbate-80, and 0.3g of tocopheryl acetate to the mixer and mix. Heat the solution to 70°C for the second time and stir continuously for 20min to obtain an oil phase. Slowly add the oil phase to the aqueous phase and shear emulsify at 2000rpm for 5min to obtain a nanoemulsion.

[0051] S2. Cool 20g of nanoemulsion to 40℃, add 2g of carbomer while stirring, continue cooling to room temperature, add 0.5g of phenoxyethanol, 0.1g of ferulic acid, 0.1g of menthol and 0.1g of fragrance in sequence, stir well, adjust the pH of the emulsion to 5.5 with triethanolamine, homogenize the emulsion with a homogenizer for 1 min at a speed of 8000 rpm and a homogenization pressure of 20MPa, defoam with a vacuum defoaming device, sterilize and then fill.

[0052] Example 2

[0053] The preparation of an oil-controlling skincare product encapsulated in cyclodextrin and azelaic acid includes the following steps:

[0054] S1. Add 850g of deionized water to a mixer, add 25g of the cyclodextrin-azeliaic acid inclusion complex prepared in Preparation Example 2, 4g of nicotinamide, and 1.5g of allantoin, and mix. Heat to 55°C for the first time and stir continuously for 25min to obtain an aqueous phase. Add 55g of glycerol, 35g of caprylic / capric triglyceride, 0.15g of polydimethylsiloxane, 0.3g of polysorbate-80, and 0.4g of tocopheryl acetate to the mixer and mix. Heat the solution to 75°C for the second time and stir continuously for 25min to obtain an oil phase. Slowly add the oil phase to the aqueous phase and shear emulsify at 2500rpm for 8min to obtain a nanoemulsion.

[0055] S2. Cool 20g of nanoemulsion to 42℃, add 2.5g of carbomer while stirring, continue cooling to room temperature, add 0.7g of phenoxyethanol, 0.2g of ferulic acid, 0.15g of menthol and 0.7g of fragrance in sequence, stir well, adjust the pH of the emulsion to 5.8 with triethanolamine, homogenize the emulsion for 1.5min with a homogenizer at a speed of 9000rpm and a homogenization pressure of 25MPa, defoam using a vacuum defoaming device, sterilize and then fill.

[0056] Example 3

[0057] The preparation of an oil-controlling skincare product encapsulated in cyclodextrin and azelaic acid includes the following steps:

[0058] S1. Add 900g of deionized water to a mixer, add 30g of the cyclodextrin-azeliaic acid inclusion complex prepared in Preparation Example 3, 6g of nicotinamide, and 2g of allantoin, and mix. Heat to 60°C for the first time and stir continuously for 30min to obtain an aqueous phase. Add 60g of glycerol, 40g of caprylic / capric triglyceride, 0.2g of polydimethylsiloxane, 1g of polysorbate-80, and 0.5g of tocopheryl acetate to the mixer and mix. Heat the solution to 80°C for the second time and stir continuously for 30min to obtain an oil phase. Slowly add the oil phase to the aqueous phase and shear emulsify at 3000rpm for 10min to obtain a nanoemulsion.

[0059] S2. Cool 20g of nanoemulsion to 45℃, add 3g of carbomer while stirring, continue cooling to room temperature, add 1g of phenoxyethanol, 0.3g of ferulic acid, 0.2g of menthol and 1g of fragrance in sequence, stir well, adjust the pH of the emulsion to 6.0 with triethanolamine, homogenize the emulsion with a homogenizer for 2 minutes at a speed of 10000rpm and a homogenization pressure of 30MPa, defoam with a vacuum defoaming device, sterilize and then fill.

[0060] Comparative Example 1

[0061] The difference between this comparative example and Example 1 is that the cyclodextrin-azeliaic acid inclusion complex is not added; the remaining steps are the same as in Example 1.

[0062] Comparative Example 2

[0063] The difference between this comparative example and Example 2 is that azelaic acid is used instead of the cyclodextrin-azelaic acid inclusion complex; the remaining steps are the same as in Example 2.

[0064] Comparative Example 3

[0065] The difference between this comparative example and Example 3 is that HP-β-CD from Example 3 is used instead of the cyclodextrin-azeliaic acid inclusion complex; the remaining steps are the same as in Example 3.

[0066] (I) In vitro sustained-release performance test: Take 1g of each of the emulsion samples from Examples 1-3 and Comparative Examples 2-3, put them into a dialysis bag with a molecular weight cutoff of 3500Da, immerse them in 200mL of phosphate buffer solution with pH=5.5 (simulating the pH of the skin surface), and shake at 100rpm in a constant temperature water bath at 37℃. Take 1mL of sample at 0.5h, 1h, 2h, 4h, 8h, 12h, and 24h (and add an equal amount of fresh buffer solution at the same time). The concentration of azelaic acid was determined by HPLC (chromatographic conditions: C18 column, mobile phase methanol:0.1% phosphoric acid=70:30, detection wavelength 210nm). The results are shown in Table 1:

[0067] Table 1. Results of in vitro sustained-release performance tests of Examples 1-3 and Comparative Examples 2-3

[0068]

[0069] (II) Oil Control Effect Test: Sixty volunteers with oily skin (half male and half female, aged 18-35) were recruited and randomly divided into 6 groups, corresponding to Examples 1-3 and Comparative Examples 1-3, respectively. After cleansing their faces, they sat quietly for 30 minutes (temperature 25±1℃, humidity 50±5%). The initial sebum amount (μg / cm²) in the T-zone of the forehead was measured using a Sebumeter. 0.5g of the corresponding sample was applied once, and the sebum amount was measured at 2h, 4h, 6h, and 8h. The average value was taken, and the sebum inhibition rate was calculated as (initial value - test value) / initial value × 100%. The results are shown in Table 2.

[0070] Table 2. Results of sebum inhibition rate (%) of Examples 1-3 and Comparative Examples 1-3

[0071]

[0072] (III) Accelerated Stability Test: The emulsions prepared in Examples 1-3 and Comparative Examples 1-3 were divided into three portions and packaged into 18 transparent glass bottles. Three storage conditions were set: ① 4℃ refrigeration (control group); ② 25℃ / 60%RH (normal storage); ③ 40℃ / 75%RH (accelerated test). After 6 months, samples were taken to detect the azelaic acid content of each emulsion (HPLC) and to observe the appearance (color, layering). The results are shown in Table 3.

[0073] Table 3. Accelerated stability test results of Examples 1-3 and Comparative Examples 1-3

[0074]

[0075] (IV) Skin irritation test: Using a Finn Chamber patch applicator, 20 μL of each sample from Examples 1-3 and Comparative Examples 1-3 were applied to the flexor surface of the forearm of 60 volunteers. The patch was left in place for 48 h. After removal, erythema / edema scores (0 points: no erythema / edema; 1 point: mild 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, and TEWL values ​​(transepidermal water loss) were recorded. The average value was calculated after statistical analysis.

[0076] A lactic acid tingling test was conducted by applying 50 μL of 5% lactic acid solution to the flexor surface of the forearm. Subjects were asked about their subjective symptoms at 2.5 min and 5 min. The scoring criteria were: 0: no tingling sensation, 1: mild tingling sensation, 2: moderate tingling sensation, and 3: severe tingling sensation. The results are shown in Tables 4 and 5.

[0077] Table 4. Results of skin irritation tests in Examples 1-3 and Comparative Examples 1-3

[0078]

[0079] Table 5. Results of lactic acid stinging test in Examples 1-3 and Comparative Examples 1-3

[0080]

[0081] As shown in Table 1, in Examples 1-3, the concentration of azelaic acid released gradually increased within 24 hours, indicating that the cyclodextrin-azelaic acid inclusion complex may have good sustained-release properties. In Comparative Example 2, azelaic acid, without cyclodextrin inclusion, had a rapid release rate, reaching a high concentration in a short time, and lacked a sustained-release effect. Comparative Example 3, using only HP-β-CD, showed a sustained-release effect of azelaic acid between that of Examples 1 and Comparative Example 2, indicating that HP-β-CD alone has a certain sustained-release effect, but it is not as significant as that of the cyclodextrin-azelaic acid inclusion complex.

[0082] Table 2 shows that the sebum inhibition rate of Examples 1-3 increased significantly over time, indicating that the cyclodextrin-azeliaic acid inclusion complex may have a good oil-controlling effect. Comparative Example 1, lacking azeliaic acid, had the worst oil-controlling effect. Comparative Example 2, where azeliaic acid was not included, had a lower oil-controlling effect than the Examples, possibly because azeliaic acid acts directly on the skin, causing greater irritation and affecting the durability of the oil-controlling effect. The oil-controlling effect of Comparative Example 3 was between that of the Examples and Comparative Example 2, indicating that HP-β-CD has a certain synergistic effect on azeliaic acid, but it is not as significant as the inclusion complex.

[0083] As shown in Table 3, in Examples 1-3, the azelaic acid content remained high and the appearance changed slightly under the conditions of 4℃, 25℃ / 60%RH, and 40℃ / 75%RH, indicating that the cyclodextrin-azelaic acid inclusion complex has good stability. In Comparative Example 2, the azelaic acid content was significantly reduced and the appearance changed significantly. The degree of reduction in azelaic acid content in Comparative Example 3 was between that of Examples 1 and Comparative Example 2.

[0084] Table 4 shows that the erythema / edema scores and TEWL values ​​of Examples 1-3 were low, indicating that the cyclodextrin-azeliaic acid inclusion complex had low skin irritation. The erythema / edema scores and TEWL values ​​of Comparative Examples 1-3 were high, indicating greater irritation.

[0085] Table 5 shows that no stinging sensation was observed in Examples 1-3, indicating that the cyclodextrin-azelaic acid inclusion complex is mild on the skin. No stinging sensation was observed in Comparative Example 1, indicating that without azelaic acid, the other components did not significantly irritate the skin. Comparative Example 2 showed moderate stinging, indicating that azelaic acid, without inclusion, acted directly on the skin, causing significant irritation. Comparative Example 3 showed mild stinging, indicating that HP-β-CD has a certain anti-sting effect on azelaic acid. In the skin irritation test and lactic acid stinging test, the cyclodextrin-azelaic acid inclusion complex reduced the direct skin irritation of azelaic acid by slowly releasing it, thus improving the product's mildness.

[0086] In summary, by adding the cyclodextrin-azelaic acid inclusion complex prepared in the preparation example, the products of Examples 1-3 have a certain oil-controlling effect, while achieving the effects of sustained release, stabilization and anti-irritation of azelaic acid, thus improving the performance and safety of skin care products.

[0087] In the description of this specification, the terms "preparation example," "example," "various examples," etc., refer to specific features, structures, materials, or characteristics described in connection with that example or preparation example, which are included in at least one example or preparation example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same example or preparation example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more examples or preparation examples.

[0088] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing an oil-controlling skincare product encapsulated in azelaic acid by cyclodextrin, characterized in that, Includes the following steps: S1. Add deionized water to a mixer, add cyclodextrin-azeliaic acid inclusion complex, nicotinamide, and allantoin, mix, heat and stir for 20-30 min to obtain an aqueous phase, add glycerol, caprylic / capric triglyceride, polydimethylsiloxane, polysorbate-80, and tocopheryl acetate, heat and stir for 20-30 min to obtain an oil phase, slowly add the oil phase to the aqueous phase, shear emulsify for 5-10 min to obtain a nanoemulsion; S2. Cool the nanoemulsion to 40-45℃, add carbomer while stirring, continue cooling to room temperature, add phenoxyethanol, ferulic acid, menthol and fragrance in sequence, adjust the pH of the emulsion with triethanolamine, homogenize with a homogenizer for 1-2 minutes, defoam, sterilize and then fill. The cyclodextrin-azelaic acid inclusion complex is prepared by the following steps: A1. Polyoxyethylene diamine was added to N-methylpyrrolidone and stirred to dissolve. Polyglutamic acid powder was added, along with N,N'-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole. The mixture was stirred and reacted at room temperature for 24-48 hours. After the reaction was completed, the copolymer solution was obtained by vacuum distillation. A2. Add HP-β-CD to N-methylpyrrolidone and stir for 20-30 min to obtain a cyclodextrin solution. Slowly add the cyclodextrin solution dropwise to the copolymer solution, add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide, control the reaction temperature at 60-70℃, and continue stirring for 6-12 h. After the reaction is completed, distill under reduced pressure to obtain the modified cyclodextrin solution. A3. Azelaic acid was added to ethanol and stirred to dissolve, resulting in an azelaic acid ethanol solution. The azelaic acid ethanol solution was slowly added dropwise to the modified cyclodextrin solution. The mixture was heated to 80-90℃ and stirred for 2-3 hours. After the reaction was completed, the reaction solution was poured into cold water to precipitate. The mixture was filtered, the filter cake was collected, washed, and dried to constant weight to obtain the cyclodextrin-azelaic acid inclusion complex. 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). In step A2, the mass ratio of HP-β-CD to 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).

2. The preparation method of a cyclodextrin-encapsulated azelaic acid oil-controlling skincare product according to claim 1, characterized in that, In step S1, the mass ratio of deionized water, cyclodextrin-azeliaic acid inclusion complex, nicotinamide, 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).

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

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

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

6. The preparation method of a cyclodextrin-encapsulated azelaic acid oil-controlling skin care product according to claim 1, characterized in that, In step A3, the mass ratio of azelaic acid to ethanol is (2-3.5):(10-18), and the mass ratio of azelaic acid ethanol solution to modified cyclodextrin solution is (5-7):(15-20).

7. The application of the method for preparing the cyclodextrin-encapsulated azelaic acid oil-controlling skin care product according to any one of claims 1-6 in the preparation of daily chemical products.

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