Azelaic acid / betaine / panthenol self-recognition des system and preparation method

Abstract

Disclosed in the present invention are an azelaic acid / betaine / panthenol self-recognition DES system and a preparation method, belonging to the technical field of supermolecules. The preparation method for the azelaic acid / betaine / panthenol self-recognition DES system of the present invention comprises the following steps: mixing azelaic acid, betaine, and panthenol according to a molar ratio of 1:(0.4-6):(0.7-10), and stirring and heating to obtain the azelaic acid / betaine / panthenol self-recognition DES system. The azelaic acid / betaine / panthenol self-recognition DES system prepared according to the present invention is readily soluble in water, and can be directly diluted by adding water until the mass concentration of azelaic acid is 0.8%-35%, without phase separation and solid precipitation, thereby effectively improving the water solubility and stability of azelaic acid, with the degree of improvement far exceeding that of the prior art.

Description

A self-identifying DES system of azelaic acid / betaine / panthenol and its preparation method Technical Field

[0001] The invention relates to an azelaic acid / betaine / panthenol self-identification DES system and a preparation method thereof, belonging to the technical field of supramolecular technology. Background Art

[0002] Azelaic acid is highly effective in preventing and treating skin problems such as acne, malignant lentigo, chloasma, melasma, malignant melanoma, and hyperpigmentation. However, azelaic acid is poorly soluble in water and oil and has a high melting point. It easily precipitates when added at high dosages, resulting in a rough and unstable system. Furthermore, the product has a limited dosage form, making it difficult to formulate water-based or refreshing products suitable for large-scale application on oily skin.

[0003] The existing technology is to form supramolecules by ultrafine grinding (CN 114181072 A), compounding organic solvents and azelaic acid (CN 110669226 A), co-crystallizing organic matter and azelaic acid (CN 112624918 A), encapsulating azelaic acid (CN 108187070 A), and preparing azelaic acid by ultrafine grinding (CN 114181072 A). A) The solubility problem of azelaic acid is solved by solubilization, plasticization and reduction of the crystal nucleation rate (CN113520890A); however, the ultrafine grinding process increases the cost of the azelaic acid raw material and fails to achieve a substantial solubilization of azelaic acid; the solubility of azelaic acid is limited when organic solvents and azelaic acid are compounded to form supramolecules, which is only increased by 3.3 times; the eutectic treatment with organic matter and azelaic acid requires a series of operations such as membrane filtration, recrystallization, and removal of organic solvents to obtain the target eutectic, which is not environmentally friendly and has a complex process; although the solubility of azelaic acid is increased to a certain extent by encapsulation treatment, the process flow is relatively complicated, and this method requires the use of a large amount of cyclodextrin, which makes the inclusion system easy to become sticky during use and has a poor skin feel; solubilization, plasticization and reduction of the crystal nucleation rate require the addition of a large amount of stabilizers to form a colloid, which inevitably hinders the penetration of azelaic acid into the skin.

[0004] Therefore, how to use a simple and green treatment process to solve the water solubility and stability of azelaic acid is an urgent problem that needs to be solved.

[0005] Summary of the Invention

[0006] [Technical Issues]

[0007] Currently, methods for increasing the water solubility of azelaic acid have the problems of complex operation, use of large amounts of organic solvents, limited solubility improvement, and impact on subsequent use.

[0008] [Technical solution]

[0009] In order to solve the above problems, the present invention selects betaine and panthenol as compatible molecules, and forms a liquid supramolecular DES system through spontaneous recognition with azelaic acid through DES modification technology, thereby improving the solubility and stability of azelaic acid, while giving the system excellent moisturizing properties, broadening the application range of azelaic acid, and allowing azelaic acid to be better integrated into water-based cosmetic formulas.

[0010] The first object of the present invention is to provide a method for preparing azelaic acid / betaine / panthenol self-identifying DES system, comprising the following steps:

[0011] Azelaic acid, betaine and panthenol are mixed in a molar ratio of 1:0.4-6:0.7-10, stirred and heated to obtain azelaic acid / betaine / panthenol self-recognition DES system.

[0012] As an embodiment of the present invention, the stirring and heating atmosphere is natural air.

[0013] As an embodiment of the present invention, the stirring and heating treatment is 350-850 rpm, 50-115° C., and 1-15 h; more preferably, the stirring and heating treatment is 350-850 rpm, 60-115° C., and 1-15 h.

[0014] As an embodiment of the present invention, the stirring and heating treatment needs to be followed by cooling to room temperature.

[0015] The second object of the present invention is a self-identifying DES system of azelaic acid / betaine / panthenol prepared by the method of the present invention, which is in liquid form.

[0016] As an embodiment of the present invention, the azelaic acid content in the azelaic acid / betaine / panthenol self-identifying DES system can be up to 50 wt%.

[0017] As an embodiment of the present invention, the azelaic acid / betaine / panthenol self-identifying DES system can remain stable for at least 24 hours without solid precipitation.

[0018] As an embodiment of the present invention, the azelaic acid / betaine / panthenol self-identifying DES system is easily soluble in water and can be directly diluted with water to a mass concentration of 0.8% to 35% azelaic acid without phase separation or solid precipitation, that is, the DES system is not destroyed.

[0019] As an embodiment of the present invention, the infrared spectrum of the azelaic acid / betaine / panthenol self-identification DES system has a wavelength of 3500-3200 cm -1 The absorption peak in the range of 1650-1700 cm corresponds to the absorption peak of hydroxyl (hydrogen bond); -1 1710cm -1 There are peaks in some places, such as small peaks.

[0020] The third object of the present invention is to use the azelaic acid / betaine / panthenol self-identification DES system described in the present invention in the field of daily chemicals or medicines.

[0021] As an embodiment of the present invention, daily chemical products include cosmetics, shampoo, mouthwash, etc.

[0022] A fourth object of the present invention is to provide a cosmetic comprising the azelaic acid / betaine / panthenol self-identifying DES system of the present invention.

[0023] As an embodiment of the present invention, the addition amount of the azelaic acid / betaine / panthenol self-identifying DES system is 0.1 to 70 wt %.

[0024] As an embodiment of the present invention, cosmetics include water-based types, refreshing types, and the like.

[0025] As an embodiment of the present invention, cosmetics include essence, essence water, spray, skin care foam, lotion, shampoo, etc.

[0026] As an embodiment of the present invention, the formula components include, by mass percentage:

[0027] Glycerin 2-4%, butylene glycol 2-4%, phenoxyethanol 0.3-0.5%, caprylyl glycol 0.3-0.5%, sphingomonas ferment extract 0.05-0.15%, sodium hyaluronate 0.04-0.06%, polyacryloyldimethyl taurate 0.05-0.15%, azelaic acid / betaine / panthenol self-identification DES system 10-30%, white willow bark extract 1-3%, EDTA2 sodium 0.04-0.06%, purslane extract 1-3%, and the rest is water.

[0028] As an embodiment of the present invention, the preparation method of the essence is as follows:

[0029] Add water, glycerin, butylene glycol, phenoxyethanol, caprylyl glycol and sodium EDTA2 into the main cup and dissolve evenly, then heat to 75°C;

[0030] Add sodium hyaluronate, Sphingomonas ferment extract, and polyacryloyldimethyl taurate to the main cup and stir well.

[0031] The mixture was cooled to 45°C, and the azelaic acid / betaine / panthenol self-identification DES system, white willow bark extract, and purslane extract were added and stirred evenly to complete the preparation.

[0032] A fifth object of the present invention is to provide a drug for removing spots and acne, which contains the azelaic acid / betaine / panthenol self-identification DES system of the present invention.

[0033] As an embodiment of the present invention, the addition amount of the azelaic acid / betaine / panthenol self-identifying DES system is 0.1 to 70 wt %.

[0034] As an embodiment of the present invention, the drug for removing spots and acne is a gel, a spray, a liquid medicine, a cream, etc.

[0035] As an embodiment of the present invention, the formula components include, by mass percentage:

[0036] Azelaic acid / betaine / panthenol self-identifying DES system 10-30%, docusate sodium 0.03-0.06%, edetate disodium 0.05-0.15%, glycerin 3-5%, poloxamer 124 0.1-0.3%, propylene glycol 3-5%, SIMULGEL 600PHA (acrylamide / sodium acryloyldimethyl taurate copolymer & isohexadecane & polysorbate 80 & sorbitan oleate) 3-5%, and the rest is water.

[0037] As an embodiment of the present invention, the preparation method of the gel drug is as follows:

[0038] (1) Preparation of active phase:

[0039] Add poloxamer 124 to water and stir evenly. Continue stirring until dissolved and clear. Then add azelaic acid / betaine / panthenol self-identifying DES system and homogenize with a homogenizer at 10000 rpm / 30 min. Set aside.

[0040] (2) Preparation of aqueous phase:

[0041] Add propylene glycol and glycerol to water and dissolve until clear, then add docusate sodium and stir at 1000 rpm until clear, and set aside;

[0042] (3) Mixing:

[0043] Add the aqueous phase and active phase into the pot in sequence, rinse the active phase beaker with water, then add SIMULGEL 600PHA and homogenize and stir at 2800 rpm for 45 minutes;

[0044] (4) Filling:

[0045] Manually fill the mixture into blank plastic tubes to obtain the gel.

[0046] A sixth object of the present invention is to provide a method for synergistically improving the moisturizing effect of azelaic acid by utilizing betaine and panthenol, comprising the following steps:

[0047] Azelaic acid, betaine, and panthenol are mixed in a molar ratio of 1:0.4-6:0.7-10, stirred, and heated to obtain an azelaic acid / betaine / panthenol self-identifying DES system with good moisturizing performance.

[0048] A seventh object of the present invention is to provide a method for improving the water solubility and stability of azelaic acid by using betaine and panthenol, comprising the following steps:

[0049] Azelaic acid, betaine and panthenol are mixed in a molar ratio of 1:0.4-6:0.7-10, stirred and heated to obtain azelaic acid / betaine / panthenol self-recognition DES system with good water solubility and stability.

[0050] [Beneficial Effects]

[0051] (1) The difficulty of DES modification technology is to screen the compatible molecules that match the target molecules. The present invention uses suitable compatible molecules (betaine, panthenol) to enable the molecules in the DES modification technology to spontaneously recognize and form supramolecular organisms according to a specific molar ratio (1:0.4:0.7 to 1:6:10), thereby improving the application pain points of the target molecule (zelaic acid) (poor solubility, low bioavailability, low safety, poor stability, etc.). Moreover, suitable compatible molecules (betaine, panthenol) can also play a synergistic role (moisturizing effect), expand the efficacy of the entire DES system, and thus expand its application prospects.

[0052] (2) The present invention uses DES modification technology to form supramolecular hydrogen bonds between molecules to change the physical state and solubility of azelaic acid, thereby preparing a transparent azelaic acid / betaine / panthenol self-identifying DES system with a maximum azelaic acid content of 50 wt%, which greatly broadens the application scenarios of azelaic acid.

[0053] (3) The azelaic acid / betaine / panthenol self-identifying DES system prepared by the present invention is easily soluble in water and can be directly diluted with water to a mass concentration of 0.8% to 35% azelaic acid without phase separation or solid precipitation, thereby effectively improving the water solubility and stability of azelaic acid, and the degree of improvement far exceeds that of the existing technology.

[0054] (4) The azelaic acid / betaine / panthenol self-recognition DES system prepared by the present invention uses betaine and panthenol as compatible ingredients, which greatly enhances the moisturizing effect of the system.

[0055] (5) The preparation process of the azelaic acid / betaine / panthenol self-recognition DES system of the present invention is simple, safe, and pollution-free. The obtained ternary liquid DES system does not require additional pre-treatment or post-treatment steps and can be directly used as a raw material in the field of medicine or daily chemical products, and is suitable for large-scale promotion. BRIEF DESCRIPTION OF THE DRAWINGS

[0056] FIG1 is an infrared spectrum of the azelaic acid / betaine / panthenol self-identification DES system of Example 1.

[0057] FIG2 is a thermogravimetric analysis curve of the azelaic acid / betaine / panthenol self-recognition DES system of Example 1.

[0058] FIG3 is a diagram showing the moisturizing performance evaluation of the azelaic acid / betaine / panthenol self-identification DES system of Example 1.

[0059] FIG4 is a diagram showing the moisturizing performance of the liquid DES system product of Comparative Example 2.

[0060] FIG5 is a graph showing the properties of samples prepared in Examples 1 to 3 and Comparative Examples 1 to 8 after being left for 24 hours.

[0061] FIG6 is a graph showing the properties of the sample prepared in Example 4 after being left for 24 hours.

[0062] FIG7 is a graph showing the properties of the sample prepared in Example 5 after being left for 24 hours. DETAILED DESCRIPTION

[0063] The following describes preferred embodiments of the present invention. It should be understood that the embodiments are for better explanation of the present invention and are not intended to limit the present invention.

[0064] Test method:

[0065] 1. Fourier transform infrared spectroscopy test:

[0066] Machine specifications: FTS6000; Machine manufacturer: Bio-ARD, USA; Experimental parameters: Scanning range: 500-4000 cm -1 , with a resolution of 4cm -1 .

[0067] 2. TGA thermogravimetric analyzer test:

[0068] Machine specifications: Mettler TGA2 SF / 1100; Machine manufacturer: Mettler Toledo, Switzerland; Experimental parameters: Temperature range: 25-450°C, heating rate: 10°C / min, experimental atmosphere: nitrogen with a flow rate of 50 mL / min.

[0069] 3. Moisturizing performance test:

[0070] The ternary liquid DES system was diluted with water to a 4% azelaic acid mass fraction and then the moisturizing performance was evaluated;

[0071] The capacitance method is used to measure the moisture content of the stratum corneum of human skin. Its principle is based on the significant difference in dielectric constant between water and other substances. The measured capacitance value of the skin varies according to the water content of the skin. The observed parameter can represent the moisture value of the skin.

[0072] Test environment conditions: The test environment temperature is 20-25℃, the humidity is 40%-60%RH, and real-time dynamic monitoring is performed;

[0073] Volunteer requirements: 40 valid volunteers, aged between 20 and 50 years old, excluding pregnant or lactating women, with a baseline value of 15-45 on the forearm test area using a capacitive skin moisture meter; no severe systemic diseases, immunodeficiency or autoimmune diseases; no active allergic diseases; no history of severe allergies to skin care cosmetics; no use of hormonal drugs or immunosuppressants in the past month; no participation in other clinical trials; use of the test substance in accordance with regulations and complete information; all volunteers should complete an informed consent form before testing;

[0074] Pre-test preparation: Do not use any products (cosmetics or topical medications) on the test area for three days prior to testing. Before the test, the subject agrees to clean the inner forearms of both hands and wipe them clean with a dry tissue. After cleaning, mark the measurement area on the inner forearms of both hands. Before the actual test, the subject should sit quietly in a standard room for at least 30 minutes, refrain from drinking, and keep their forearms exposed and in the test position, remaining relaxed.

[0075] Data test: first measure the blank value of the test area (data at T0), then press 2.0±0.1mg / cm 2 Use a latex fingertip to evenly apply the test product to the test area. Measure the skin moisture content of the test area 2, 4, and 5 hours after application. Each person is tested 5 times each time, with 8 people in a group, and the average value is calculated.

[0076] 4. High and low temperature cycle test:

[0077] The system was stored at -5°C and 40°C in a cycle for 15 times. Specifically, the supramolecular self-assembly system was frozen at -5°C and then dissolved at 40°C. This was repeated 1 time, and the state after each dissolution was observed to maintain a stable and uniform liquid state without solid precipitation.

[0078] The raw materials used in the embodiment are:

[0079] Azelaic acid: particle size 500 nm to 100 μm, particle size has no effect, the particle size selected in the examples and comparative examples is 30 μm, commercially available;

[0080] Panthenol: D-panthenol or DL-panthenol, both of which can be used in the Examples and Comparative Examples, are commercially available;

[0081] Sphingomonas fermentation extract: purchased from Shanghai Youshi Industrial Co., Ltd.

[0082] Polyacryloyldimethyltaurate: 99%, purchased from Wuhan Lvjing Fenghua Biotechnology Co., Ltd.;

[0083] White willow bark extract: purchased from Xi'an Green Sky Biotechnology Co., Ltd.;

[0084] Sodium EDTA2: 99%, purchased from Shanghai Yuanye Biotechnology Co., Ltd.;

[0085] Portulaca oleracea extract: purchased from Shanghai Huiwen Biotechnology Co., Ltd.

[0086] % mentioned in the Examples and Comparative Examples without any specific meaning is mass percentage.

[0087] Example 1

[0088] A method for preparing azelaic acid / betaine / panthenol self-identifying DES system comprises the following steps:

[0089] 0.01 mol of azelaic acid, 0.01 mol of betaine, and 0.02 mol of D-panthenol were mixed and placed in a container. The mixture was stirred and heated at 500 rpm and 95°C for 5 h in a natural air atmosphere to obtain a transparent and uniform liquid azelaic acid / betaine / panthenol self-identifying DES system.

[0090] The mass fraction of azelaic acid in the azelaic acid / betaine / panthenol self-recognition DES system is 26%;

[0091] The azelaic acid / betaine / panthenol self-recognizing DES system was diluted with water to a mass concentration of 5% azelaic acid. After dilution, the system did not undergo phase separation and solid precipitation, that is, the DES system was not destroyed;

[0092] The self-identifying DES system of azelaic acid / betaine / panthenol and the system diluted with water were subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times). In the end, both systems were able to maintain a stable and uniform liquid state without solid precipitation.

[0093] After the azelaic acid / betaine / panthenol self-identification DES system was left at room temperature for 24 hours, samples were taken and characterized using infrared spectroscopy and TGA thermogravimetric analysis. The test results are as follows:

[0094] Figure 1 shows the test results of infrared spectrum. As can be seen from Figure 1: 3500~3200cm -1 The absorption peak in the range of 1650-1700 cm corresponds to the absorption peak of hydroxyl (hydrogen bond). In Example 1, the peak in this band shifts to a lower wave number. -1 The peak at 1710 cm corresponds to the stretching vibration of the carbonyl group. Compared with the three single molecules, the liquid DES system in Example 1 derived a peak at 1710 cm -1 The peak at the bottom of the spectrum is small and tends to shift to higher wavelengths. This is due to the formation of hydrogen bonds by the carbonyl oxygen in the system, which leads to a change in its electron cloud density. These results indicate that hydrogen bonds are formed in the DES system.

[0095] Figure 2 shows the TGA dynamic thermogravimetric analysis curve. It shows that the weight loss temperature of the azelaic acid / betaine / panthenol self-recognition DES system is moderate, and the overall weight loss trend is slower than that of the individual molecules. This also indicates, to some extent, that azelaic acid, betaine, and panthenol form a new organic unity.

[0096] The moisturizing performance of the azelaic acid / betaine / panthenol self-identifying DES system was evaluated after it was diluted with water to a 4% azelaic acid mass fraction. The results are shown in Figure 3. As can be seen from Figure 3, the water content of the human epidermis increased significantly and the water would not be lost for a long time, indicating that the system has good moisturizing performance.

[0097] Example 2

[0098] A method for preparing azelaic acid / betaine / panthenol self-identifying DES system comprises the following steps:

[0099] 0.01 mol of azelaic acid, 0.02 mol of betaine, and 0.05 mol of DL-panthenol were mixed and placed in a container. The mixture was stirred and heated at 450 rpm and 90°C for 4 hours in a natural air atmosphere to obtain a transparent and uniform liquid azelaic acid / betaine / panthenol self-recognition DES system.

[0100] The mass fraction of azelaic acid in the azelaic acid / betaine / panthenol self-recognition DES system is 13%;

[0101] The azelaic acid / betaine / panthenol self-identifying DES system was diluted with water to a mass concentration of 1% azelaic acid. After dilution, the system did not undergo phase separation and solid precipitation, that is, the DES system was not destroyed.

[0102] The self-identifying DES system of azelaic acid / betaine / panthenol and the system diluted with water were subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times). In the end, both systems were able to maintain a stable and uniform liquid state without solid precipitation.

[0103] The moisturizing performance of the azelaic acid / betaine / panthenol self-identifying DES system was evaluated after diluting it with water to a 4% azelaic acid mass fraction. The results are as follows:

[0104] The average moisture content was 28 at 0h, 47 at 2h, 45 at 4h, and 42 at 5h.

[0105] Example 3

[0106] A method for preparing azelaic acid / betaine / panthenol self-identifying DES system comprises the following steps:

[0107] 0.01 mol of azelaic acid, 0.015 mol of betaine, and 0.04 mol of DL-panthenol were mixed and placed in a container. The mixture was stirred and heated at 600 rpm and 105°C for 3 hours in a natural air atmosphere to obtain a transparent and uniform liquid azelaic acid / betaine / panthenol self-recognition DES system.

[0108] The mass fraction of azelaic acid in the azelaic acid / betaine / panthenol self-identification DES system is 16%;

[0109] The azelaic acid / betaine / panthenol self-identifying DES system was diluted with water to a mass concentration of 10% azelaic acid. After dilution, the system did not undergo phase separation and solid precipitation, that is, the DES system was not destroyed.

[0110] The self-identifying DES system of azelaic acid / betaine / panthenol and the system diluted with water were subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times). In the end, both systems were able to maintain a stable and uniform liquid state without solid precipitation.

[0111] The moisturizing performance of the azelaic acid / betaine / panthenol self-identifying DES system was evaluated after diluting it with water to a 4% azelaic acid content. The results are as follows:

[0112] The average moisture content was 31 at 0h, 49 at 2h, 46 at 4h, and 44 at 5h.

[0113] Example 4

[0114] A method for preparing azelaic acid / betaine / panthenol self-identifying DES system comprises the following steps:

[0115] 0.01 mol of azelaic acid, 0.01 mol of betaine, and 0.02 mol of D-panthenol were mixed and placed in a container. The mixture was stirred and heated at 500 rpm and 50°C for 1 hour in a natural air atmosphere to obtain a transparent and uniform liquid azelaic acid / betaine / panthenol self-recognition DES system.

[0116] The mass fraction of azelaic acid in the azelaic acid / betaine / panthenol self-recognition DES system is 26%;

[0117] The azelaic acid / betaine / panthenol self-recognizing DES system was diluted with water to a mass concentration of 5% azelaic acid. After dilution, the system did not undergo phase separation and solid precipitation, that is, the DES system was not destroyed;

[0118] The self-identifying DES system of azelaic acid / betaine / panthenol and the system diluted with water were subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times). In the end, both systems were able to maintain a stable and uniform liquid state without solid precipitation.

[0119] Example 5

[0120] A method for preparing azelaic acid / betaine / panthenol self-identifying DES system comprises the following steps:

[0121] 0.01 mol of azelaic acid, 0.01 mol of betaine, and 0.02 mol of D-panthenol were mixed and placed in a container. The mixture was stirred and heated at 500 rpm and 60°C for 1 hour in a natural air atmosphere to obtain a transparent and uniform liquid azelaic acid / betaine / panthenol self-recognition DES system.

[0122] The mass fraction of azelaic acid in the azelaic acid / betaine / panthenol self-recognition DES system is 26%;

[0123] The azelaic acid / betaine / panthenol self-recognizing DES system was diluted with water to a mass concentration of 5% azelaic acid. After dilution, the system did not undergo phase separation and solid precipitation, that is, the DES system was not destroyed;

[0124] The self-identifying DES system of azelaic acid / betaine / panthenol and the system diluted with water were subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times). In the end, both systems were able to maintain a stable and uniform liquid state without solid precipitation.

[0125] Comparative Example 1

[0126] On the basis of Example 1, D-panthenol was omitted, and other procedures remained the same as in Example 1 to obtain a product.

[0127] The obtained product was subjected to performance testing, and the test results are as follows:

[0128] Compared to Example 1, attempts to develop a self-identifying DES system using only betaine as a single component failed to produce a homogeneous, transparent, and stable liquid system. After 24 hours at room temperature, the system became a solid-liquid mixture. Diluting the solid-liquid mixture with water to a 5% azelaic acid concentration after 24 hours at room temperature failed to produce a homogeneous, transparent aqueous solution, with solid precipitation.

[0129] Comparative Example 2

[0130] On the basis of Example 1, betaine was omitted, and other procedures remained the same as in Example 1 to obtain a product.

[0131] The obtained product was subjected to performance testing, and the test results are as follows:

[0132] Compared with Example 1, the use of panthenol as the sole compatibility component in the self-identifying DES system resulted in a homogeneous, transparent, and stable liquid DES system. The liquid DES system in this comparative example was diluted with water to a 5% azelaic acid concentration, yielding a homogeneous, transparent aqueous solution with no solid precipitation.

[0133] At the same time, the moisturizing performance of the system product of this comparative example was evaluated, and the results are shown in Figure 4:

[0134] As can be seen from FIG4 , the water content of the human epidermis also increases to a certain extent, but compared with the system of Example 1, the water content increase is not high, and the water loss rate is faster in terms of long-term moisturizing ability.

[0135] Comparative Example 3

[0136] The amount of betaine in Example 1 was adjusted to 0.07 mol, and the other ingredients were kept consistent with those in Example 1 to obtain the product.

[0137] The obtained product was subjected to performance testing, and the test results are as follows:

[0138] Compared with Example 1, simply increasing the amount of betaine did not produce a uniform, transparent, and stable liquid self-identification system. After 24 hours at room temperature, the system was a solid-liquid mixture. Diluting the solid-liquid mixture with water to a 5% azelaic acid concentration after 24 hours at room temperature did not produce a uniform, transparent aqueous solution, and solids precipitated.

[0139] Comparative Example 4

[0140] The amount of azelaic acid in Example 1 was adjusted to 0.03 mol, and the other ingredients were kept consistent with Example 1 to obtain the product.

[0141] The obtained product was subjected to performance testing, and the test results are as follows:

[0142] Compared to Example 1, simply increasing the amount of azelaic acid did not produce a uniform, transparent, and stable liquid self-identification system. After 24 hours at room temperature, the system became a solid-liquid mixture. Diluting the solid-liquid mixture with water to a 5% azelaic acid concentration after 24 hours at room temperature did not produce a uniform, transparent aqueous solution, and solids precipitated.

[0143] Comparative Example 5

[0144] The heating temperature in Example 1 was adjusted to 45° C., while other conditions remained the same as in Example 1 to obtain the product.

[0145] The obtained product was subjected to performance testing, and the test results are as follows:

[0146] Compared with Example 1, simply lowering the heating temperature did not yield a uniform, transparent, and stable liquid self-identification system. After standing at room temperature for 24 hours, the solid-liquid mixture was diluted with water to a 5% azelaic acid concentration. However, a uniform, transparent aqueous solution was not obtained, and solids precipitated.

[0147] Comparative Example 6

[0148] The heating temperature in Example 1 was adjusted to 120° C., while other conditions remained the same as in Example 1 to obtain the product.

[0149] The obtained product was subjected to performance testing, and the test results are as follows:

[0150] Compared with Example 1, a uniform, transparent, and stable liquid system can be obtained by simply increasing the heating temperature. However, the color of the system is significantly darker and a more pungent odor is produced. It is speculated that another chemical reaction may have occurred during the reaction process or that a component in the system has decomposed.

[0151] Comparative Example 7

[0152] The heating time in Example 1 was adjusted to 40 min, while other conditions remained the same as in Example 1 to obtain the product.

[0153] The obtained product was subjected to performance testing, and the test results are as follows:

[0154] Compared with Example 1, simply shortening the heating time did not produce a uniform, transparent, and stable liquid self-identification system. After 24 hours at room temperature, the system was a solid-liquid mixture. Diluting the solid-liquid mixture with water to a 5% azelaic acid concentration after 24 hours at room temperature did not produce a uniform, transparent aqueous solution, and solids precipitated.

[0155] Comparative Example 8

[0156] The betaine in Example 1 was adjusted to theanine, and the other aspects were kept consistent with Example 1 to obtain the product.

[0157] The obtained product was subjected to performance testing, and the test results are as follows:

[0158] Compared to Example 1, when only one of the system components was changed, theanine was used instead of betaine. A homogeneous, transparent, and stable liquid self-identification system could not be obtained. After 24 hours at room temperature, the system became a solid-liquid mixture. Diluting the solid-liquid mixture with water to a 5% azelaic acid concentration after 24 hours at room temperature did not produce a homogeneous, transparent aqueous solution, and solids precipitated.

[0159] Comparative Example 9

[0160] The betaine in Example 1 was adjusted to lauryl betaine, and the other contents were kept consistent with those in Example 1 to obtain a product.

[0161] The obtained product was subjected to performance testing, and the test results are as follows:

[0162] Compared to Example 1, when only one of the system components was changed, lauryl betaine was used instead of betaine. A homogeneous, transparent, and stable liquid self-identification system could not be obtained. After 24 hours at room temperature, the system became a solid-liquid mixture. Diluting the solid-liquid mixture with water to a 5% azelaic acid concentration after 24 hours at room temperature did not produce a homogeneous, transparent aqueous solution, and solids precipitated.

[0163] Comparative Example 10

[0164] The betaine in Example 1 was adjusted to sorbitol, and the other parts were kept consistent with Example 1 to obtain the product.

[0165] The obtained product was subjected to performance testing, and the test results are as follows:

[0166] Compared to Example 1, when only one of the system components was changed, sorbitol was used in place of betaine. A homogeneous, transparent, and stable liquid self-identification system could not be obtained. After 24 hours at room temperature, the system became a solid-liquid mixture. Diluting the solid-liquid mixture with water to a 5% azelaic acid concentration after 24 hours at room temperature did not produce a homogeneous, transparent aqueous solution, and solids precipitated.

[0167] Comparative Example 11

[0168] The D-panthenol in Example 1 was replaced with glycerol, and the other conditions remained the same as in Example 1 to obtain the product.

[0169] The obtained product was subjected to performance testing, and the test results are as follows:

[0170] Compared to Example 1, when only one of the system's ingredients was changed, using glycerol instead of panthenol, a homogeneous, transparent, and stable liquid self-identification system was not obtained. After 24 hours at room temperature, the system became a solid-liquid mixture. Diluting the solid-liquid mixture with water to a 5% azelaic acid concentration after 24 hours at room temperature did not produce a homogeneous, transparent aqueous solution, and solids precipitated.

[0171] Comparative Example 12

[0172] The D-panthenol in Example 1 was adjusted to a mixture of polyethylene glycol 400 and propylene glycol (mass ratio of 3:1), and the other ingredients were kept consistent with Example 1 to obtain a product.

[0173] The obtained product was subjected to performance testing, and the test results are as follows:

[0174] Compared to Example 1, only one of the system's ingredients was changed: a mixture of polyethylene glycol 400 and propylene glycol was used instead of panthenol. However, a homogeneous, transparent, and stable liquid self-identification system could not be obtained. After 24 hours at room temperature, the system became a solid-liquid mixture. Diluting the solid-liquid mixture with water to a 5% azelaic acid concentration after 24 hours at room temperature did not produce a homogeneous, transparent aqueous solution, and solids precipitated.

[0175] Comparative Example 13

[0176] The D-panthenol in Example 1 was adjusted to propylene glycol or polyethylene glycol 400, and the other ingredients were kept the same as in Example 1 to obtain the product.

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

[0178] Compared to Example 1, when only one of the system components was changed, using propylene glycol or polyethylene glycol 400 instead of panthenol, a homogeneous, transparent, and stable liquid self-identification system could not be obtained. After 24 hours at room temperature, the system became a solid-liquid mixture. After 24 hours at room temperature, the solid-liquid mixture was diluted with water to a 5% azelaic acid concentration. A homogeneous, transparent aqueous solution could not be obtained, and solids precipitated.

[0179] Application of Example 6 in cosmetics

[0180] The azelaic acid / betaine / panthenol self-identifying DES system prepared in Example 1 was used to prepare an essence. The specific formula is shown in Table 1 below:

[0181] Table 1 Essence formula

[0182] The preparation method is as follows:

[0183] Add ingredients 1 to 5 and 11 to the main cup and dissolve evenly, then heat to 75°C;

[0184] Add ingredients 6 to 8 into the main cup and stir well;

[0185] Cool to 45°C, add raw materials No. 9, 10, and 12, stir evenly, and the preparation is complete.

[0186] The stability test of the essence was carried out according to the GB / T 26367-2010 standard, and the results showed that the stability of the essence was qualified; moreover, the prepared essence had certain moisturizing and acne-removing effects.

[0187] Comparative Example 14

[0188] According to the formula of the essence in Table 1, the azelaic acid / betaine / panthenol self-identifying DES system of Example 1 was replaced with 5.26% w / w azelaic acid, 3.28% w / w betaine, and 11.46% w / w D-panthenol to prepare the essence as shown in Table 2 below;

[0189] The preparation process is:

[0190] Add ingredients 1 to 5 and 13 to the main cup and dissolve evenly, then heat to 75°C;

[0191] Add ingredients 6 to 8 into the main cup and stir well;

[0192] Cool to 45°C, add raw materials No. 9 to 12 and No. 14, stir evenly, and the preparation is complete.

[0193] The essence was tested for stability according to GB / T 26367-2010 standard and failed the stability test with solid precipitation.

[0194] Table 2 Essence formula

[0195] Example 7 Application in Medicine

[0196] The azelaic acid / betaine / panthenol self-recognition DES system prepared in Example 1 was used to prepare a gel for removing spots and acne. The specific formula is shown in Table 3.

[0197] Table 3 Gel formulations

[0198] The preparation method is as follows:

[0199] (1) Preparation of active phase:

[0200] Add poloxamer 124 to water and stir evenly. Continue stirring until dissolved and clear. Then add the azelaic acid / betaine / panthenol self-identifying DES system of Example 1. Homogenize with a homogenizer at 10000 rpm / 30 min and set aside.

[0201] (2) Preparation of aqueous phase:

[0202] Add propylene glycol and glycerol to water and dissolve until clear, then add docusate sodium and stir at 1000 rpm until clear, and set aside;

[0203] (3) Mixing:

[0204] Add the aqueous phase and active phase into the pot in sequence, rinse the active phase beaker with water, then add SIMULGEL 600PHA and homogenize and stir at 2800 rpm for 45 minutes;

[0205] (4) Filling:

[0206] Manually fill the mixture into blank plastic tubes to obtain a gel for treating acne.

[0207] The obtained gel was subjected to a stability test, and the results showed that the stability was qualified, no solid precipitation was found, and the gel had a certain effect in removing spots and acne.

[0208] Although the present invention has been disclosed above in terms of preferred embodiments, 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 / betaine / panthenol self-identifying DES system, characterized in that: The steps include: Azelaic acid, betaine and panthenol are mixed in a molar ratio of 1:0.4-6:0.7-10, stirred and heated to obtain azelaic acid / betaine / panthenol self-identifying DES system.

2. The method according to claim 1, characterized in that The stirring and heating treatment is carried out at 350 to 850 rpm and 50 to 115° C. for 1 to 15 hours.

3. The method according to claim 1, characterized in that The atmosphere for stirring and heating is natural air.

4. The method according to claim 1, characterized in that After the stirring and heating treatment, the mixture needs to be cooled to room temperature.

5. Azelaic acid / betaine / panthenol self-identifying DES system prepared by the method according to any one of claims 1 to 4.

6. The azelaic acid / betaine / panthenol self-identification DES system according to claim 5, characterized in that: The maximum azelaic acid content in the azelaic acid / betaine / panthenol self-recognizing DES system can reach 50 wt%.

7. Application of the azelaic acid / betaine / panthenol self-identification DES system according to claim 5 in the field of daily chemicals or preparation of medicines.

8. A cosmetic, characterized in that: It contains the azelaic acid / betaine / panthenol self-identification DES system as described in claim 5.

9. The cosmetic according to claim 8, characterized in that: The addition amount of the azelaic acid / betaine / panthenol self-identifying DES system is 0.1 to 70 wt%.

10. The cosmetic according to claim 8, characterized in that: Cosmetics are one of the following: essence, essence water, spray, skin care foam, lotion, and shampoo.

11. The cosmetic according to claim 8, characterized in that: The formula components include by mass percentage: Glycerin 2-4%, butylene glycol 2-4%, phenoxyethanol 0.3-0.5%, caprylyl glycol 0.3-0.5%, sphingomonas fermentation extract 0.05-0.15%, sodium hyaluronate 0.04-0.06%, polyacryloyldimethyl taurate 0.05-0.15%, azelaic acid / betaine / panthenol self-identification DES system 10-30%, white willow bark extract 1-3%, EDTA2 sodium 0.04-0.06%, purslane extract 1-3%, and the rest is water.

12. The cosmetic according to claim 8, characterized in that: The cosmetics are water-based or refreshing.

13. A drug for removing spots and acne, characterized in that: It contains the azelaic acid / betaine / panthenol self-identification DES system as described in claim 5.

14. The drug according to claim 13, characterized in that The medicine is one of a gel, a spray, a liquid medicine and an ointment.

15. The drug according to claim 13, characterized in that The addition amount of the azelaic acid / betaine / panthenol self-identifying DES system is 0.1 to 70 wt%.

16. The drug according to claim 13, characterized in that The formula components include by mass percentage: Azelaic acid / betaine / panthenol self-identifying DES system 10-30%, docusate sodium 0.03-0.06%, edetate disodium 0.05-0.15%, glycerol 3-5%, poloxamer 124 0.1-0.3%, propylene glycol 3-5%, SIMULGEL 600PHA 3-5%, and the rest is water.

17. A method for utilizing betaine and panthenol to synergistically enhance the moisturizing effect of azelaic acid, characterized in that: The steps include: Azelaic acid, betaine and panthenol are mixed in a molar ratio of 1:0.4-6:0.7-10, stirred and heated to obtain azelaic acid / betaine / panthenol self-identifying DES system with good moisturizing effect.

18. A method for improving the water solubility and stability of azelaic acid by using betaine and panthenol, characterized in that: The steps include: Azelaic acid, betaine and panthenol are mixed in a molar ratio of 1:0.4-6:0.7-10, stirred and heated to obtain azelaic acid / betaine / panthenol self-identifying DES system with good water solubility and stability.

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