Azelaic acid liquid DES system with synergistic whitening and enhancement and preparation method thereof

Abstract

The present invention discloses a liquid DES system of azelaic acid with synergistic whitening and enhancement and a preparation method thereof, and belongs to the field of supramolecular technology. The method for preparing a liquid DES system of azelaic acid with synergistic whitening and enhancement in the present invention comprises: (1) ultrasonically mixing azelaic acid, niacinamide and panthenol according to a molar ratio of 1:0.5:1 to 1:5:9 to obtain a mixture; (2) heating the mixture under a nitrogen atmosphere to obtain a liquid DES system of azelaic acid with synergistic whitening and enhancement. The present invention selects panthenol and niacinamide as the compatible components of azelaic acid to form a DES system, which is different from the conventional DES solvent system, because the addition of the other two compatible components gives DES more efficacy, especially the synergistic effect of niacinamide and azelaic acid, which enhances the original efficacy of azelaic acid while also significantly improving skin pigmentation, and has excellent whitening and antioxidant effects.

Description

Technical Field

[0001] The invention relates to a liquid azelaic acid DES system with synergistic whitening and enhancement effect and a preparation method thereof, belonging to the technical field of supramolecular. Background Art

[0002] Azelaic acid is an organic compound with antioxidant, anti-inflammatory, antibacterial and exfoliating effects. Therefore, it is widely used in personal care products. Azelaic acid is an effective antioxidant and skin conditioner that can neutralize free radicals on the skin surface to prevent skin damage due to oxidation. It can also promote skin cell regeneration and improve skin texture. Most of the related products on the market currently use various emulsification systems to make azelaic acid into creams. At the same time, in order to ensure its bioavailability and effective concentration, the amount of azelaic acid added needs to be increased to 15-20%, which undoubtedly increases the risk of skin irritation. In addition, some of the existing azelaic acid-related products also cause a sense of gravel during use because azelaic acid is easy to precipitate, which affects the efficacy and brings a very poor experience to users. The main reason for the above defects is the poor water solubility of azelaic acid. The water solubility problem of azelaic acid also brings great difficulties to the related cosmetic formulations and dosage form design.

[0003] Solving the water solubility problem of azelaic acid can greatly enhance its application prospects and market competitiveness. At present, some literatures have disclosed some methods for improving the water solubility of azelaic acid, such as: Patent CN 113248364 A discloses a method of using alkaline substances (such as theophylline, echinine, carnitine, etc.) to compound with azelaic acid to form salts, thereby increasing the water solubility of azelaic acid, but the preparation process requires a large amount of organic solvents and the process is relatively complicated; Patent CN 110669226 A discloses a method for preparing a polyethylene glycol / propylene glycol / zelaic acid supramolecular system, which uses propylene glycol and polyethylene glycol as solvents to first dissolve azelaic acid, and then adds the dissolved system to a large amount of water while hot; propylene glycol and polyethylene glycol are commonly used solvents and solubilizers in cosmetic formulas. This method is essentially the thermal dissolution of azelaic acid under the solubilization of conventional alcohols and polyethylene glycol, so the solubility of azelaic acid can only be increased by 3.33 times at most, that is, about 8g / L; Patent CN 114181072 A discloses a process for preparing ultrafine azelaic acid, which improves the water solubility of azelaic acid to a certain extent. However, the preparation of ultrafine powder increases the cost of azelaic acid raw materials and fails to achieve a substantial solubilization of azelaic acid.

[0004] However, these methods have limited effect on improving the water solubility of azelaic acid, require a large amount of organic solvents, and are more complicated to operate. Summary of the invention

[0005] In order to solve the above problems, the present invention utilizes DES modification technology to connect each compatible component through intermolecular hydrogen bonds or intermolecular interactions to form a supramolecular organism with stable components, thereby improving the solubility and stability of azelaic acid, reducing its irritation, and improving its efficacy. At the same time, the present invention selects panthenol and niacinamide as compatible components of azelaic acid to form a DES system, which is different from the conventional DES solvent system because the addition of the other two compatible components gives DES more efficacy, especially niacinamide and azelaic acid synergistically, which enhances the original efficacy of azelaic acid while also significantly improving skin pigmentation, and has excellent whitening and antioxidant effects.

[0006] The first object of the present invention is to provide a method for preparing azelaic acid liquid DES system with synergistic whitening and enhancement, comprising the following steps:

[0007] (1) ultrasonically mixing azelaic acid, niacinamide and panthenol to obtain a mixture;

[0008] (2) The mixture is heated under a nitrogen atmosphere to obtain a liquid DES system of azelaic acid having synergistic whitening effect.

[0009] Furthermore, in step (1), the molar ratio of azelaic acid, niacinamide and panthenol is 1:0.5:1 to 1:5:9.

[0010] Furthermore, in step (1), the power of ultrasonic mixing is 200 to 800 W, and the time is 5 to 40 minutes.

[0011] Furthermore, the heating treatment in step (2) is performed at 200-1000 rpm and 65-115° C. for 2-18 hours.

[0012] The second object of the present invention is a liquid DES system of azelaic acid with synergistic whitening and enhancing effect prepared by the method described in the present invention.

[0013] Furthermore, the azelaic acid liquid DES system with synergistic whitening and enhancement is a liquid system and can be directly used as a raw material in cosmetic formulations.

[0014] Furthermore, the liquid DES system of azelaic acid with synergistic whitening and enhancement is an organic supramolecular whole formed by intermolecular hydrogen bonds. The system can still maintain stability after being diluted 1 to 30 times with water, without precipitation of solid particles, and can effectively improve the water solubility of azelaic acid.

[0015] Furthermore, the azelaic acid liquid DES system with synergistic whitening and enhancement can significantly improve skin problems. Niacinamide and azelaic acid work synergistically with each other, enhancing the original efficacy of azelaic acid while also significantly improving skin pigmentation, and has excellent whitening and antioxidant effects.

[0016] The third object of the present invention is to use the azelaic acid liquid DES system with synergistic whitening and enhancement in personal care products.

[0017] The fourth object of the present invention is to provide a cosmetic, which adopts the azelaic acid liquid DES system with synergistic whitening and enhancement effect described in the present invention.

[0018] Furthermore, the amount of the azelaic acid liquid DES system with synergistic whitening and enhancement effect added to the cosmetics is 0.1 to 70 wt%.

[0019] Furthermore, the cosmetics are whitening and antioxidant cosmetics.

[0020] The fifth object of the present invention is to provide a method for inhibiting melanin production and removing free radicals, which uses the azelaic acid liquid DES system with synergistic whitening and enhancement effect described in the present invention.

[0021] The sixth object of the present invention is to provide a method for improving the water solubility and stability of azelaic acid by using panthenol and niacinamide, comprising the following steps:

[0022] (1) ultrasonically mixing azelaic acid, niacinamide and panthenol to obtain a mixture;

[0023] (2) The mixture is heated under a nitrogen atmosphere to obtain a nonanedioic acid liquid DES system with good water solubility and stability.

[0024] The beneficial effects of the present invention are as follows:

[0025] (1) The present invention uses DES modification technology to connect azelaic acid, niacinamide, and panthenol through intermolecular hydrogen bonds or intermolecular interactions to form a supramolecular organism with stable components, thereby effectively improving the water solubility of azelaic acid. After the DES system is diluted 1 to 30 times with water, it can still maintain a stable liquid system (the azelaic acid content after dilution is 0.5% to 25%) without solid particle precipitation, which can effectively solve its defects in subsequent cosmetic formulation applications.

[0026] (2) The present invention selects niacinamide as one of the compatible ingredients of azelaic acid. Niacinamide and azelaic acid act synergistically with each other, enhancing the original efficacy of azelaic acid while also significantly improving skin pigmentation, and has excellent whitening and antioxidant effects.

[0027] (3) The azelaic acid liquid DES system with synergistic whitening and enhancement in the present invention can be directly used as a raw material or combined into cosmetic formulas or product applications without the need for special treatment such as separation and purification; its preparation method is simple and green, does not require the use of any organic solvents, and all components are 100% converted, making it suitable for large-scale promotion.

[0028] (4) The DES (Deep Eutectic Solvent) used in the present invention is a new type of solvent system, which is composed of deep eutectic substances and belongs to the category of supramolecular systems. DES has the advantages of low cost, easy preparation, good reproducibility, low toxicity and environmental friendliness, and has therefore attracted widespread attention in the fields of chemistry, energy and materials science. In terms of molecular modification and improvement of application effects, DES modification technology has great application prospects. First, as a solvent, DES has a large solubility and can dissolve and stabilize various active ingredients. Secondly, DES can be used as an alternative solvent for sustainable development, replacing traditional organic solvents and reducing pollution and harm to the environment. In addition, DES can also improve the molecular properties by screening suitable compatibility, such as changing texture, enhancing permeability, solubility and stability.

[0029] (5) The panthenol used in the present invention, also known as provitamin B5, can promote the metabolism of skin cells, repair damaged skin barriers, and enhance the skin's resistance to external stimuli. In addition, panthenol also has anti-inflammatory and soothing effects, can relieve skin inflammation, and improve skin redness, swelling, itching and other discomfort symptoms.

[0030] (6) The niacinamide used in the present invention, also known as nicotinamide, has excellent whitening, anti-wrinkle, anti-oxidation and skin barrier repair functions, and is widely used in various skin care and beauty products; by inhibiting the production of melanin, niacinamide can effectively reduce spots, improve uneven skin tone, and make the skin brighter and more even. At the same time, niacinamide can also stimulate the production of collagen, increase skin elasticity, and thus reduce the appearance of wrinkles. In addition, niacinamide also has anti-inflammatory and repair effects, can relieve skin inflammation, repair damaged skin barriers, and improve the skin's resistance to external stimuli. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is the infrared spectrum of the azelaic acid liquid DES system of Example 1.

[0032] Figure 2 This is the thermogravimetric analysis diagram of the azelaic acid liquid DES system of Example 1.

[0033] Figure 3 The properties of the samples prepared in Examples 1 to 3 and Comparative Examples 1 to 8 after being left for 24 hours. DETAILED DESCRIPTION

[0034] The preferred embodiments of the present invention are described below. It should be understood that the embodiments are for better explaining the present invention and are not used to limit the present invention.

[0035] The present invention provides a method for preparing azelaic acid liquid DES system with synergistic whitening and enhancement, comprising the following steps:

[0036] (1) ultrasonically mixing azelaic acid, niacinamide and panthenol to obtain a mixture;

[0037] (2) The mixture is heated under a nitrogen atmosphere to obtain a liquid DES system of azelaic acid having synergistic whitening effect.

[0038] In the present invention, the molar ratio of azelaic acid, niacinamide and panthenol in step (1) is 1:0.5:1 to 1:5:9, preferably 1:0.5:1 to 1:5:5, and more preferably 1:0.5:1 to 1:3:5; specifically, in an embodiment of the present invention, it can be 1:0.5:2, 1:1:3 or 1:2:5.

[0039] In the present invention, the power of ultrasonic mixing in step (1) is 200-800 W, and the time is 5-40 min; the power is preferably 300-800 W, and more preferably 500-600 W; specifically, in an embodiment of the present invention, it can be 500 W or 600 W; the time is preferably 10-35 min, and more preferably 15-30 min; specifically, in an embodiment of the present invention, it can be 15 min, 22 min, or 30 min.

[0040] In the present invention, the heating treatment in step (2) is 200-1000rpm, 65-115°C, and heating for 2-18h; the rotation speed is preferably 300-800rpm, more preferably 400-600rpm, and specifically, in the embodiments of the present invention, it can be 500rpm, 600rpm; the temperature is preferably 75-105°C, more preferably 80-100°C; specifically, in the embodiments of the present invention, it can be 80°C, 90°C or 100°C; the time is preferably 3-10h, more preferably 3-6h; specifically, in the embodiments of the present invention, it can be 3h, 5h or 6h.

[0041] In the present invention, the azelaic acid liquid DES system can still maintain stability without precipitation of solid particles after being diluted 1 to 30 times with water; specifically, in an embodiment of the present invention, it can be diluted 1 times, 5 times, or 30 times with water, and the corresponding final mass fraction of azelaic acid in the aqueous solution can be 10%, 2.6%, or 0.93%.

[0042] Test method:

[0043] (1) Fourier transform infrared spectroscopy test:

[0044] Machine specifications: FTS6000;

[0045] Machine manufacturer: Bio-ard, USA;

[0046] Experimental parameters: Scanning range 500~4000cm-1 , resolution 4cm -1 .

[0047] (2) TGA thermogravimetric analyzer test:

[0048] Machine specifications: Mettler TGA2 SF / 1100;

[0049] Machine manufacturer: Mettler Toledo, Switzerland;

[0050] Experimental parameters: temperature range is 25-450°C, heating rate is 10°C / min, experimental atmosphere is nitrogen and the flow rate is 50mL / min.

[0051] (3) Whitening and antioxidant performance test:

[0052] With reference to the "Evaluation Standards for Cosmetic Efficacy Claims", the azelaic acid liquid DES system was diluted to an azelaic acid content of 1%, and then the tyrosinase activity inhibition rate, B16 melanocyte proliferation activity inhibition rate, and free radical scavenging were measured.

[0053] (4) High and low temperature cycle test:

[0054] The supramolecular assembly system was frozen at -5°C and then placed at 40°C to dissolve. This was considered one cycle and was repeated thereafter. It was observed that the state after each dissolution could maintain a stable uniform liquid state without solid precipitation. The example was data from 15 cycles.

[0055] The raw materials used in the examples are:

[0056] Niacinamide: white crystalline powder, purity 99%, commercially available;

[0057] Azelaic acid: particle size 500nm-100μm, particle size has no effect, the particle size selected in the examples and comparative examples is 40μm, commercially available;

[0058] Panthenol: D-panthenol or DL-panthenol, both of which can be used in the examples and comparative examples, are commercially available;

[0059] Sphingomonas fermentation extract: purchased from Shanghai Youshi Industrial Co., Ltd.;

[0060] Polyacryloyldimethyltaurate: 99%, purchased from Wuhan Lvjing Fenghua Biotechnology Co., Ltd.;

[0061] White willow bark extract: purchased from Xi'an Green Sky Biotechnology Co., Ltd.;

[0062] EDTA2 sodium: 99%, purchased from Shanghai Yuanye Biotechnology Co., Ltd.;

[0063] Portulaca oleracea extract: purchased from Shanghai Huiwen Biotechnology Co., Ltd.;

[0064] % mentioned in the Examples and Comparative Examples without any specific meaning is mass percentage.

[0065] Example 1

[0066] A method for preparing azelaic acid liquid DES system with synergistic whitening and enhancement, comprising the following steps:

[0067] (1) 0.01 mol of azelaic acid, 0.01 mol of niacinamide, and 0.03 mol of DL-panthenol were mixed by ultrasonication (500 W) for 22 min to obtain a mixture;

[0068] (2) The mixture was heated at 500 rpm and 90° C. for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a uniform and transparent liquid DES system of azelaic acid with synergistic whitening effect.

[0069] The mass fraction of azelaic acid in the azelaic acid liquid DES system with synergistic whitening and enhancement is 20%; when it is diluted 1 times with water, it can still maintain stability without solid particles precipitating, and the mass fraction of azelaic acid in the diluted system is 10%; the azelaic acid liquid DES system and the diluted system are subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times), and finally both systems can maintain a stable and uniform liquid state without solid precipitation.

[0070] After the uniform, transparent and stable azelaic acid liquid DES system was placed for 24 hours, a sample was taken and characterized by infrared spectrometer and TGA thermogravimetric analysis. The results are as follows: Figure 1 and Figure 2 :

[0071] Figure 1 Fourier infrared spectroscopy test results, from Figure 1 It can be seen that: 3500~3200cm -1 The absorption peak in the range of 3355cm corresponds to the absorption peak of hydroxyl group (hydrogen bond); compared with panthenol, the azelaic acid liquid DES system forms a wider peak in this range, and the peak of the azelaic acid liquid DES system in Example 1 is from 3355cm -1 Move to lower wavenumber direction to 3348 cm -1 This indicates that a large amount of hydrogen is formed in the azelaic acid liquid DES system obtained in Example 1. 1650cm -1 ~1700cm -1 The peaks around 1720 cm-1 correspond to the stretching vibration of the carbonyl group. -1The peaks on the left and right sides of the DES system move to higher wavenumbers. This is due to the change in the carbonyl electron cloud density caused by the generation of a large number of hydrogen bonds within the DES system. The above results all confirm that azelaic acid, niacinamide, and panthenol molecules interact strongly and generate a large number of hydrogen bonds.

[0072] Figure 2 is the TGA dynamic thermogravimetric analysis curve. Figure 2 It can be seen that the initial weight loss temperature of the azelaic acid liquid DES system in Example 1 is lower than that of the other three monomer components, and the overall weight loss trend is slower than that of the three monomer components, which also indirectly indicates that the three form an organic whole through hydrogen bonds.

[0073] After adding water to dilute the azelaic acid liquid DES system obtained in this example to azelaic acid content of 1%, the tyrosinase activity inhibition rate, B16 melanocyte proliferation activity inhibition rate, and free radical scavenging were measured. The test results are shown in Table 1:

[0074] Table 1

[0075] Measurement items Test Results Tyrosinase inhibition rate 91.56％ Melanin production inhibition rate 85.37％ Superoxide anion radical removal rate 84.68％ Hydroxyl free radical removal rate 81.46％

[0076] Example 2

[0077] A method for preparing azelaic acid liquid DES system with synergistic whitening and enhancement, comprising the following steps:

[0078] (1) 0.01 mol of azelaic acid, 0.005 mol of niacinamide, and 0.02 mol of D-panthenol were mixed by ultrasonication (600 W) for 15 min to obtain a mixture;

[0079] (2) The mixture was heated at 600 rpm and 100° C. for 3 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a uniform and transparent liquid DES system of azelaic acid with synergistic whitening effect.

[0080] The mass fraction of azelaic acid in the azelaic acid liquid DES system with synergistic whitening and enhancement is 28%; it can still maintain stability when diluted 30 times with water, and no solid particles are precipitated. The mass fraction of azelaic acid in the diluted system is 0.93%; the azelaic acid liquid DES system and the diluted system are subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times), and finally both systems can maintain a stable and uniform liquid state without solid precipitation.

[0081] After adding water to dilute the azelaic acid liquid DES system obtained in this example to azelaic acid content of 1%, the tyrosinase activity inhibition rate, B16 melanocyte proliferation activity inhibition rate, and free radical scavenging were measured. The test results are shown in Table 2:

[0082] Table 2

[0083] Measurement items Test Results Tyrosinase inhibition rate 90.35％ Melanin production inhibition rate 86.38％ Superoxide anion radical removal rate 85.66％ Hydroxyl free radical removal rate 80.75％

[0084] Example 3

[0085] A method for preparing azelaic acid liquid DES system with synergistic whitening and enhancement, comprising the following steps:

[0086] (1) 0.01 mol of azelaic acid, 0.02 mol of niacinamide and 0.05 mol of DL-panthenol were mixed by ultrasonication (500 W) for 30 min to obtain a mixture;

[0087] (2) The mixture was heated at 500 rpm and 80° C. for 6 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a uniform and transparent liquid DES system of azelaic acid with synergistic whitening effect.

[0088] The mass fraction of azelaic acid in the azelaic acid liquid DES system with synergistic whitening and enhancement is 13%; it can still maintain stability after being diluted 5 times with water, and no solid particles are precipitated. The mass fraction of azelaic acid in the diluted system is 2.6%; the azelaic acid liquid DES system and the diluted system are subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times), and finally both systems can maintain a stable and uniform liquid state without solid precipitation.

[0089] After adding water to dilute the azelaic acid liquid DES system obtained in this example to azelaic acid content of 1%, the tyrosinase activity inhibition rate, B16 melanocyte proliferation activity inhibition rate, and free radical scavenging were measured. The test results are shown in Table 3:

[0090] Table 3

[0091] Measurement items Test Results Tyrosinase inhibition rate 91.76％ Melanin production inhibition rate 86.33％ Superoxide anion radical removal rate 84.87％ Hydroxyl free radical removal rate 81.34％

[0092] Comparative Example 1

[0093] Based on Example 1, panthenol was omitted, and the rest was the same as Example 1, specifically as follows:

[0094] (1) 0.01 mol of azelaic acid and 0.01 mol of nicotinamide were ultrasonically mixed (500 W) for 22 min to obtain a mixture;

[0095] (2) The mixture was heated at 500 rpm and 90° C. for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a product.

[0096] The obtained product was tested and found to be:

[0097] Compared with Example 1, only nicotinamide was selected as a single compatibility component to try the DES system, and a uniform, transparent, and stable liquid system could not be obtained, and the system was solid. The solid in this comparative example was diluted by half with water, and a uniform, transparent aqueous solution could not be obtained, and solid particles were present.

[0098] Comparative Example 2

[0099] Based on Example 1, niacinamide was omitted, and the rest was consistent with Example 1, specifically as follows:

[0100] (1) 0.01 mol of azelaic acid and 0.03 mol of DL-panthenol were mixed by ultrasonication (500 W) for 22 min to obtain a mixture;

[0101] (2) The mixture was heated at 500 rpm and 90° C. for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a product.

[0102] The obtained product was tested and found to be:

[0103] Compared with Example 1, only panthenol was selected as a single compatibility component to try the DES system, and a uniform, transparent and stable liquid system was obtained. The system in this comparative example was diluted by 1 times with water to obtain a uniform, transparent aqueous solution.

[0104] After adding water to dilute the uniform and transparent aqueous solution to azelaic acid content of 1%, the tyrosinase activity inhibition rate, B16 melanocyte proliferation activity inhibition rate, and free radical scavenging were measured. The test results are shown in Table 4:

[0105] Table 4

[0106] Measurement items Test Results Tyrosinase inhibition rate 70.24％ Melanin production inhibition rate 62.15％ Superoxide anion radical removal rate 64.39％ Hydroxyl free radical removal rate 67.95％

[0107] It can be seen from Table 4 that the product system of this comparative example has improved the inhibition rate of tyrosinase and melanin synthesis, and also has a certain free radical scavenging effect. However, compared with Example 1, the overall whitening and antioxidant effect is significantly lower than that of Example 1.

[0108] Comparative Example 3

[0109] The nicotinamide in Example 1 was adjusted to lysine, and the rest was consistent with Example 1, specifically as follows:

[0110] (1) 0.01 mol of azelaic acid, 0.01 mol of lysine, and 0.03 mol of DL-panthenol were mixed by ultrasonication (500 W) for 22 min to obtain a mixture;

[0111] (2) The mixture was heated at 500 rpm and 90° C. for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a product.

[0112] The obtained product was subjected to performance test, and the test results are as follows:

[0113] Compared with Example 1, only one of the system's compatible components was changed, and lysine was selected to try to replace nicotinamide. A uniform, transparent, and stable liquid system could not be obtained, and the system after being placed at room temperature for 24 hours was a solid-liquid mixed system; the solid-liquid mixed system after being placed at room temperature for 24 hours was diluted 1 times with water, and a uniform, transparent aqueous solution could not be obtained, and solid particles were present.

[0114] Comparative Example 4

[0115] The nicotinamide in Example 1 was adjusted to glutathione, and the rest was consistent with Example 1, specifically as follows:

[0116] (1) 0.01 mol of azelaic acid, 0.01 mol of glutathione, and 0.03 mol of DL-panthenol were mixed by ultrasonication (500 W) for 22 min to obtain a mixture;

[0117] (2) The mixture was heated at 500 rpm and 90° C. for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a product.

[0118] The obtained product was subjected to performance test, and the test results are as follows:

[0119] Compared with Example 1, only one of the system's compatible components was changed, and glutathione was selected to try to replace nicotinamide. A uniform, transparent, and stable liquid system could not be obtained, and the system after being placed at room temperature for 24 hours was a solid-liquid mixed system; the solid-liquid mixed system after being placed at room temperature for 24 hours was diluted 1 times with water, and a uniform, transparent aqueous solution could not be obtained, and solid particles existed.

[0120] Comparative Example 5

[0121] The nicotinamide in Example 1 was adjusted to nicotinic acid, and the rest was consistent with Example 1, as follows:

[0122] (1) 0.01 mol of azelaic acid, 0.01 mol of nicotinic acid, and 0.03 mol of DL-panthenol were mixed by ultrasonication (500 W) for 22 min to obtain a mixture;

[0123] (2) The mixture was heated at 500 rpm and 90° C. for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a product.

[0124] The obtained product was subjected to performance test, and the test results are as follows:

[0125] Compared with Example 1, only one of the system's compatible components was changed, and nicotinic acid was selected to try to replace nicotinamide. A uniform, transparent, and stable liquid system could not be obtained, and the system after being placed at room temperature for 24 hours was a solid-liquid mixed system; the solid-liquid mixed system after being placed at room temperature for 24 hours was diluted 1 time with water, and a uniform, transparent aqueous solution could not be obtained, and solid particles were present.

[0126] Comparative Example 6

[0127] The panthenol in Example 1 was adjusted to polyethylene glycol 400, and the other ingredients were the same as in Example 1, specifically as follows:

[0128] (1) 0.01 mol of azelaic acid, 0.01 mol of nicotinamide, and 0.03 mol of polyethylene glycol 400 were ultrasonically mixed (500 W) for 22 min to obtain a mixture;

[0129] (2) The mixture was heated at 500 rpm and 90°C for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain the product.

[0130] The obtained product was subjected to performance test, and the test results are as follows:

[0131] Compared with Example 1, only one of the system's compatible components was changed, that is, polyethylene glycol 400 was selected to try to replace panthenol, but a uniform and transparent liquid system could not be obtained; the system after being placed at room temperature for 24 hours was a solid-liquid mixed system; the solid-liquid mixed system after being placed at room temperature for 24 hours was diluted 1 times with water, but a uniform and transparent aqueous solution could not be obtained, and solid particles were present.

[0132] Comparative Example 7

[0133] The panthenol in Example 1 is adjusted to propylene glycol, and the other parts are consistent with Example 1, specifically as follows:

[0134] (1) 0.01 mol of azelaic acid, 0.01 mol of niacinamide, and 0.03 mol of propylene glycol were ultrasonically mixed (500 W) for 22 min to obtain a mixture;

[0135] (2) The mixture was heated at 500 rpm and 90°C for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain the product.

[0136] The obtained product was subjected to performance test, and the test results are as follows:

[0137] The results showed that: compared with Example 1, by changing only one of the system's compatible components, i.e., using propylene glycol to replace panthenol, a uniform and transparent liquid system could not be obtained; the system after being placed at room temperature for 24 hours was a solid-liquid mixed system; the solid-liquid mixed system after being placed at room temperature for 24 hours was diluted 1 times with water, but a uniform and transparent aqueous solution could not be obtained, and solid particles were present.

[0138] Comparative Example 8

[0139] The panthenol in Example 1 was adjusted to be a mixture of polyethylene glycol 400 and propylene glycol (mass ratio of 3:1), and the other contents were the same as in Example 1, as follows:

[0140] (1) 0.01 mol of azelaic acid, 0.01 mol of a mixture of polyethylene glycol 400 and propylene glycol (mass ratio of 3:1) and 0.03 mol of propylene glycol were ultrasonically mixed (500 W) for 22 min to obtain a mixture;

[0141] (2) The mixture was heated at 500 rpm and 90°C for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain the product.

[0142] The obtained product was subjected to performance test, and the test results are as follows:

[0143] The results showed that, compared with Example 1, when only one of the system's compatible components was changed, i.e., a mixture of polyethylene glycol 400 and propylene glycol was used to replace panthenol, a uniform and transparent liquid system could not be obtained; the system after being placed at room temperature for 24 hours was a solid-liquid mixed system; when the solid-liquid mixed system after being placed at room temperature for 24 hours was diluted 1 times with water, a uniform and transparent aqueous solution could not be obtained, and solid particles were present.

[0144] Comparative Example 9

[0145] The amount of nicotinamide in Example 1 was adjusted to 0.06 mol, and the other contents were kept the same as in Example 1, as follows:

[0146] (1) 0.01 mol of azelaic acid, 0.06 mol of niacinamide, and 0.03 mol of DL-panthenol were mixed by ultrasonication (500 W) for 22 min to obtain a mixture;

[0147] (2) The mixture was heated at 500 rpm and 90° C. for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a product.

[0148] The obtained product was subjected to performance test, and the test results are as follows:

[0149] Compared with Example 1, only increasing the feeding amount of nicotinamide cannot obtain a uniform, transparent, and stable liquid system, and the system is a solid-liquid mixed system after being placed at room temperature for 24 hours. The solid-liquid mixed system after being placed at room temperature for 24 hours was diluted by 1 times with water, and a uniform, transparent aqueous solution could not be obtained, and solid particles existed.

[0150] Comparative Example 10

[0151] The amount of azelaic acid in Example 1 was adjusted to 0.025 mol, and the other ingredients were kept the same as in Example 1, as follows:

[0152] (1) 0.0025 mol of azelaic acid, 0.01 mol of niacinamide and 0.03 mol of DL-panthenol were mixed by ultrasonication (500 W) for 22 min to obtain a mixture;

[0153] (2) The mixture was heated at 500 rpm and 90° C. for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a product.

[0154] The obtained product was subjected to performance test, and the test results are as follows:

[0155] Compared with Example 1, only increasing the amount of azelaic acid does not result in a uniform, transparent, and stable liquid system. The system after being placed at room temperature for 24 hours is a solid-liquid mixed system. The solid-liquid mixed system after being placed at room temperature for 24 hours is diluted by 1 times with water. A uniform, transparent aqueous solution cannot be obtained, and solid particles exist.

[0156] Comparative Example 11

[0157] The heating temperature in Example 1 was adjusted to 60° C., and the other parameters were kept the same as in Example 1, as follows:

[0158] (1) 0.01 mol of azelaic acid, 0.01 mol of niacinamide, and 0.03 mol of DL-panthenol were mixed by ultrasonication (500 W) for 22 min to obtain a mixture;

[0159] (2) The mixture was heated at 500 rpm and 60° C. for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a product.

[0160] The obtained product was subjected to performance test, and the test results are as follows:

[0161] Compared with Example 1, only lowering the heating temperature cannot obtain a uniform, transparent, and stable liquid system, and the system after being placed at room temperature for 24 hours is a solid-liquid mixed system. The solid-liquid mixed system after being placed at room temperature for 24 hours is diluted by 1 times with water, and a uniform, transparent aqueous solution cannot be obtained, and solid particles exist.

[0162] Comparative Example 12

[0163] The heating temperature in Example 1 was adjusted to 120° C., and the other parameters were kept the same as in Example 1, as follows:

[0164] (1) 0.01 mol of azelaic acid, 0.01 mol of niacinamide, and 0.03 mol of DL-panthenol were mixed by ultrasonication (500 W) for 22 min to obtain a mixture;

[0165] (2) The mixture was heated at 120° C. at 500 rpm for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a product.

[0166] The obtained product was subjected to performance test, and the test results are as follows:

[0167] Compared with Example 1, only by increasing the heating temperature, a uniform, transparent and stable liquid system can be obtained, but the color of the system becomes darker and the viscosity becomes significantly larger, which indicates that a chemical reaction may have occurred during the reaction. After the solid-liquid mixed system was placed at room temperature for 24 hours, it was diluted by 1 times with water, and a uniform, transparent aqueous solution could not be obtained, and an oily substance insoluble in water existed.

[0168] Comparative Example 13

[0169] The heating time in Example 1 was adjusted to 1.5 h, and the rest was consistent with Example 1, as follows:

[0170] (1) 0.01 mol of azelaic acid, 0.01 mol of niacinamide, and 0.03 mol of DL-panthenol were mixed by ultrasonication (500 W) for 22 min to obtain a mixture;

[0171] (2) The mixture was heated at 500 rpm and 90° C. for 1.5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a product.

[0172] The obtained product was subjected to performance test, and the test results are as follows:

[0173] Compared with Example 1, only shortening the heating time cannot obtain a uniform, transparent, and stable liquid system, and the system after being placed at room temperature for 24 hours is a solid-liquid mixed system. The solid-liquid mixed system after being placed at room temperature for 24 hours is diluted by 1 times with water, and a uniform, transparent aqueous solution cannot be obtained, and solid particles exist.

[0174] Comparative Example 14

[0175] The ultrasonic mixing step in Example 1 is omitted, and the rest is consistent with Example 1, specifically as follows:

[0176] 0.01 mol of azelaic acid, 0.01 mol of nicotinamide and 0.03 mol of DL-panthenol were heated at 500 rpm and 90° C. for 5 h under a nitrogen atmosphere, and then cooled to room temperature to obtain a product.

[0177] The obtained product was subjected to performance test, and the test results are as follows:

[0178] Compared with Example 1, ultrasonic mixing was omitted, and a uniform, transparent, and stable liquid system could not be obtained. The system after being placed at room temperature for 24 hours was a solid-liquid mixed system. The solid-liquid mixed system after being placed at room temperature for 24 hours was diluted by 1 times with water, and a uniform, transparent aqueous solution could not be obtained, and solid particles existed.

[0179] Example 4 Application in cosmetics

[0180] The azelaic acid liquid DES system with synergistic whitening and enhancement prepared in Example 1 was used to prepare an essence, and the formula of the essence is shown in Table 5:

[0181] The preparation method of the essence is as follows:

[0182] Add ingredients 1 to 5 and 11 into the main cup and dissolve evenly;

[0183] Heat to 75℃, add ingredients 6 to 8 into the main cup and stir evenly;

[0184] Cool down to 45℃, add raw materials No. 9, 10 and 12, stir evenly, and the preparation is complete.

[0185] The stability of the essence was tested according to GB / T 26367-2010 standard, and the results showed that the stability of the essence was qualified.

[0186] Table 5 Essence formula

[0187] Serial number Raw material name %w / w 1 water To100 2 glycerin 3 3 Butanediol 3 4 Phenoxyethanol, 0.4 5 Caprylyl Glycol 0.4 6 Sphingomonas fermentation extract 0.1 7 Sodium Hyaluronate 0.05 8 Polyacryloyldimethyltaurate 0.1 9 Example 1 Azelaic acid liquid DES system with synergistic whitening effect 25 10 White Willow Bark Extract 2 11 Sodium EDTA2 0.05 12 Purslane Extract 2

[0188] Comparative Example 15

[0189] According to the formula of the essence in Table 5, the azelaic acid liquid DES system with synergistic whitening and synergistic effect in Example 1 is replaced with 5.075% w / w azelaic acid, 3.3% w / w niacinamide, and 16.625% w / w DL-panthenol, as shown in Table 6 below:

[0190] Table 6 Essence formula

[0191] Serial number Raw material name %w / w 1 water To100 2 glycerin 3 3 Butanediol 3 4 Phenoxyethanol, 0.4 5 Caprylyl Glycol 0.4 6 Sphingomonas fermentation extract 0.1 7 Sodium Hyaluronate 0.05 8 Polyacryloyldimethyltaurate 0.1 9 Azelaic acid 5.075 10 Niacinamide 3.3 11 DL-Panthenol 16.625 12 White Willow Bark Extract 2 13 Sodium EDTA2 0.05 14 Purslane Extract 2

[0192] The preparation method of the essence is as follows:

[0193] Add ingredients No. 1 to 5 and No. 13 into the main cup and dissolve evenly;

[0194] Heat to 75℃, add ingredients 6 to 8 into the main cup and stir evenly;

[0195] Cool down to 45℃, add raw materials No. 9 to 12 and 14, stir evenly, and the preparation is completed.

[0196] The stability of the essence was tested according to GB / T 26367-2010 standard and the stability was unqualified with solid precipitation.

[0197] Although the present invention has been disclosed as above in the form of a preferred embodiment, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

Claims

1. A method for preparing azelaic acid liquid DES system with synergistic whitening and enhancement, characterized in that: The steps include: (1) ultrasonically mixing azelaic acid, niacinamide and panthenol to obtain a mixture; wherein the molar ratio of azelaic acid, niacinamide and panthenol is 1:0.5:1 to 1:5:9; the power of ultrasonic mixing is 200 to 800 W, and the time is 5 to 40 minutes; (2) The mixture is heated under a nitrogen atmosphere to obtain a liquid DES system of azelaic acid having synergistic whitening and enhancing effects; wherein the heating treatment is performed at 200 to 1000 rpm and 65 to 115° C. for 2 to 18 hours.

2. The azelaic acid liquid DES system with synergistic whitening and enhancement prepared by the method described in claim 1.

3. Use of the azelaic acid liquid DES system with synergistic whitening and enhancement effect as claimed in claim 2 in personal care products.

4. A cosmetic, characterized in that: The azelaic acid liquid DES system with synergistic whitening and enhancement effect as described in claim 2 is adopted.

5. The cosmetic according to claim 4, characterized in that: The addition amount of the azelaic acid liquid DES system with synergistic whitening and enhancement effect in cosmetics is 0.1 to 70 wt%.

6. A method for improving the water solubility and stability of azelaic acid by using panthenol and niacinamide, characterized in that: The steps include: (1) ultrasonically mixing azelaic acid, niacinamide and panthenol to obtain a mixture; wherein the molar ratio of azelaic acid, niacinamide and panthenol is 1:0.5:1 to 1:5:9; the power of ultrasonic mixing is 200 to 800 W, and the time is 5 to 40 minutes; (2) The mixture is heated under a nitrogen atmosphere to obtain a nonanedioic acid liquid DES system with good water solubility and stability; wherein the heating treatment is performed at 200-1000 rpm and 65-115° C. for 2-18 hours.

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