A water-soluble azelaic acid system and preparation method thereof

Abstract

The present invention discloses a water-soluble azelaic acid system and a preparation method thereof, and belongs to the field of supramolecular technology. The method for preparing a water-soluble azelaic acid system described in the present invention comprises the following steps: uniformly mixing azelaic acid, salicylic acid and panthenol, stirring and heating at 65 to 110° C. for 1 to 8 hours, so that azelaic acid, salicylic acid and panthenol form a liquid organic body through intermolecular hydrogen bonds, that is, a water-soluble azelaic acid system. The present invention selects salicylic acid and panthenol as compatible molecules, and mixes and heats them together with azelaic acid, so that azelaic acid, salicylic acid and panthenol form a liquid organic body through intermolecular hydrogen bonds, which effectively improves the solubility of azelaic acid, and does not require the use of a large amount of solvent, and the operation is also very simple. In addition, salicylic acid as a compatible molecule can synergistically improve the exfoliating ability of azelaic acid.

Description

Technical Field

[0001] The invention relates to a water-soluble azelaic acid system and a preparation method thereof, belonging to the technical field of supramolecular. Background Art

[0002] Azelaic acid is a functional ingredient commonly used in cosmetics. It is mainly used to treat acne and reduce inflammation. It also has good moisturizing ability, which can help the skin absorb and retain moisture, thereby increasing the softness and radiance of the skin. It has antioxidant properties, can neutralize free radicals, reduce the damage of oxidative stress to the skin, and prevent skin aging and the formation of fine lines. These excellent characteristics have made azelaic acid gradually become a star raw material in the cosmetics field in recent years.

[0003] Even so, azelaic acid has major application defects in cosmetic applications. For example, the solubility of azelaic acid in water is low (2.4g / L), which requires special processes or the addition of other auxiliary dissolving agents to increase its solubility when preparing water-based cosmetics; in an alkaline environment, azelaic acid is easily decomposed, and its efficacy is greatly reduced; azelaic acid may interact with other ingredients in some cases, such as certain antioxidants, sunscreens or metal ions, affecting the stability and efficacy of the product. Therefore, pH and compatibility issues need to be considered when designing the formula and selecting other ingredients.

[0004] In order to solve the water solubility problem of azelaic acid, the existing technology has made some efforts. For example:

[0005] Patent CN 113248364A discloses a method for increasing the water solubility of azelaic acid by compounding alkaline substances (such as theophylline, echinine, carnitine, etc.) with azelaic acid to form salts, but the preparation process requires a large amount of organic solvents and the process is relatively complicated;

[0006] Patent CN 114181072A 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.

[0007] Patent CN 112624918A discloses a co-crystal of azelaic acid and an organic base and a preparation method thereof, wherein the solid co-crystal is prepared in an organic solvent under an inert gas, and a series of operations such as membrane filtration, recrystallization, and removal of the organic solvent are required to obtain the target co-crystal, which is not environmentally friendly and has a complicated process. In addition, the patent does not clearly indicate the specific solubilization value of azelaic acid.

[0008] Patent CN 108187070A discloses a method for preparing azelaic acid-cyclodextrin inclusion complex by cyclodextrin inclusion and spray drying. Although the solubility of azelaic acid is increased to a certain extent, the process flow is relatively complicated and a large amount of cyclodextrin is required, which makes the inclusion system easy to become sticky during use and has a poor skin feel.

[0009] However, these methods are complicated to operate, require the use of a large amount of solvent, and the improvement of water solubility is not obvious.

[0010] Supramolecular system is a technology that makes different molecules form an organic whole through hydrogen bonds, π-π stacking, van der Waals forces and other non-covalent bonds. Using supramolecular technology, a single molecule can not only maintain its original efficacy, but also improve its own solubility, bioavailability, stability and other properties, and even play a synergistic role through the selection of compatible molecules.

[0011] At present, some people have adopted supramolecular technology to improve the water solubility of azelaic acid. For example, patent CN 110669226A discloses a method for preparing a polyethylene glycol / propylene glycol / zelaic acid supramolecular system. In this method, propylene glycol and polyethylene glycol are used as solvents to first dissolve azelaic acid, and then the dissolved system is added to a large amount of water while hot. However, propylene glycol and polyethylene glycol are commonly used solvents and solubilizers in cosmetic formulas. In essence, this method is the thermal dissolution of azelaic acid in the presence of conventional alcohol and polyethylene glycol solubilizers, and the solubility of azelaic acid can only be increased by 3.33 times at most, that is, about 8 g / L. Summary of the invention

[0012] In order to solve the above problems, the present invention selects salicylic acid and panthenol as the compatible molecules, and mixes and heats them with azelaic acid, so that azelaic acid, salicylic acid, and panthenol form a liquid organic body through intermolecular hydrogen bonds, which effectively improves the solubility of azelaic acid, and does not require a large amount of solvent, and the operation is very simple. In addition, salicylic acid as a compatible molecule can synergistically improve the exfoliating ability of azelaic acid.

[0013] Salicylic acid is a commonly used oil-soluble cosmetic exfoliant ingredient. It has excellent efficacy and can effectively dissolve the stratum corneum accumulated on the surface of the skin, gently remove old keratin cells, and make the skin smoother and softer. Salicylic acid also has a deep cleansing effect, penetrating into the pores to absorb and remove dirt, oil and dead skin. This can not only reduce the formation of blackheads and acne, but also improve the texture and brightness of the skin. In addition, salicylic acid also has anti-inflammatory and antibacterial properties, which can relieve inflammatory reactions, reduce bacterial growth, and help improve acne and other skin problems.

[0014] Panthenol is a vitamin B5 derivative that acts as a deeply penetrating moisturizer, stimulates epithelial cell growth, promotes wound healing, and acts as an anti-inflammatory.

[0015] The first object of the present invention is to provide a method for preparing a water-soluble azelaic acid system, comprising the following steps:

[0016] Evenly mix azelaic acid, salicylic acid and panthenol, and heat with stirring at 65-110° C. for 1-8 hours, so that azelaic acid, salicylic acid and panthenol form a liquid organic body, i.e., a water-soluble azelaic acid system, through intermolecular hydrogen bonds.

[0017] Optionally, the molar ratio of azelaic acid, salicylic acid and panthenol is 1:0.3-15:1-12.

[0018] Optionally, the atmosphere for stirring and heating is air, argon or carbon dioxide.

[0019] Optionally, the rotation speed of stirring and heating is 300 to 1000 rpm.

[0020] The second object of the present invention is a water-soluble azelaic acid system prepared by the method of the present invention.

[0021] Optionally, the maximum azelaic acid content in the water-soluble azelaic acid system can reach 43 wt%.

[0022] Optionally, the water-soluble azelaic acid system can be directly used as a stable liquid raw material in the cosmetic or pharmaceutical fields without any post-treatment.

[0023] Optionally, the water-soluble azelaic acid system can be gradually diluted with water until the azelaic acid accounts for 1% of the total mass fraction of the aqueous solution, and it can still remain stable for a long time without phase separation or solid precipitation.

[0024] Optionally, salicylic acid as one of the compatible ingredients can effectively regulate body pH and slightly maintain the acid-base balance of the skin; so that the pH range of the resulting water-soluble azelaic acid system is 2.0-6.0; and salicylic acid can also synergistically enhance the exfoliating effect of azelaic acid in the water-soluble azelaic acid system.

[0025] The third object of the present invention is the application of the water-soluble azelaic acid system of the present invention in the field of cosmetics or pharmacy.

[0026] The fourth object of the present invention is to provide a cosmetic comprising the water-soluble azelaic acid system of the present invention.

[0027] Optionally, the water-soluble azelaic acid system is used in an amount of 1 to 50 wt%.

[0028] Optionally, in addition to the water-soluble azelaic acid system, the cosmetics may also contain one or more of glycerin, sphingomonas fermentation extract, sodium hyaluronate, oligosaccharides, marine oligosaccharides, ascorbic acid, white willow bark extract, purslane extract, etc.

[0029] Optionally, the cosmetics include essence, essence water, spray, skin care foam, lotion, shampoo, etc.

[0030] Optionally, cosmetics can be used for exfoliation, moisturizing, antibacterial, acne and anti-inflammatory purposes.

[0031] The fifth object of the present invention is to provide a medicine containing the water-soluble azelaic acid system of the present invention.

[0032] Optionally, the water-soluble azelaic acid system is used in an amount of 1 to 50 wt%.

[0033] Optionally, the drug has a water-soluble azelaic acid system as a main component.

[0034] Optionally, the medicine is in the form of a gel, a spray, a liquid, a cream, etc.

[0035] A sixth object of the present invention is to provide a method for improving the exfoliating performance of azelaic acid by using salicylic acid and panthenol, wherein the method uses the water-soluble azelaic acid system of the present invention.

[0036] The seventh object of the present invention is to provide a method for synergistically improving the water solubility of azelaic acid by using salicylic acid and panthenol, comprising the following steps:

[0037] Evenly mix azelaic acid, salicylic acid and panthenol, and heat with stirring at 65-110° C. for 1-8 hours, so that azelaic acid, salicylic acid and panthenol form a liquid organic body, i.e., a water-soluble azelaic acid system, through intermolecular hydrogen bonds.

[0038] Beneficial effects of the present invention:

[0039] (1) The water-soluble azelaic acid system prepared by the present invention is a liquid, wherein the azelaic acid content can be up to 43%, providing sufficient design space for subsequent application in cosmetic formulations.

[0040] (2) In the water-soluble azelaic acid system prepared by the present invention, azelaic acid, salicylic acid and panthenol interact with each other through supramolecular hydrogen bonds to form an organic whole, thereby effectively improving the water solubility of azelaic acid; the obtained system can be gradually diluted with water until azelaic acid accounts for 1% of the total mass fraction of the aqueous solution, and can still remain stable for more than 24 hours without phase separation or solid precipitation.

[0041] (3) The water-soluble azelaic acid system prepared by the present invention uses salicylic acid as one of the compatible ingredients, which can effectively regulate body pH, maintain the acid-base balance of the skin, and can also synergistically enhance the exfoliating effect of azelaic acid; at the same time, the system of the present invention synergistically improves the water solubility of azelaic acid to a certain extent.

[0042] (4) The water-soluble azelaic acid system prepared by the present invention has a simple, safe and easy-to-operate preparation process, and the prepared system can be directly applied to cosmetic or pharmaceutical formulations without any post-treatment, and is suitable for industrial promotion. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 This is the infrared spectrum of the water-soluble azelaic acid system of Example 1.

[0044] Figure 2 This is the thermogravimetric analysis curve of the water-soluble azelaic acid system of Example 1.

[0045] 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

[0046] 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.

[0047] Test method:

[0048] 1. Fourier infrared spectroscopy test:

[0049] Machine specifications: FTS6000;

[0050] Machine manufacturer: Bio-ard, USA;

[0051] Experimental parameters: Scanning range 500~4000cm -1 , resolution 4cm -1 .

[0052] 2. TGA thermogravimetric analyzer test:

[0053] Machine specifications: Mettler TGA2 SF / 1100;

[0054] Machine manufacturer: Mettler Toledo, Switzerland;

[0055] 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.

[0056] 3. Exfoliation effect test:

[0057] Use German CK skin texture scanner Visioscan (VC20) to test the stratum corneum of human skin:

[0058] Including initial value testing, product use, efficacy testing, and statistical analysis, the samples are tested in accordance with the physical and chemical testing methods in Chapter 4 of the "Technical Specifications for Safety of Cosmetics":

[0059] (1) Test subjects and test conditions:

[0060] In a constant temperature test environment with a temperature of (21±1)℃ and a humidity of (40-60)%, 30 volunteers with more stratum corneum at the elbows were selected;

[0061] Inclusion criteria: ① Aged 20 to 45 years, all indoor workers (except pregnant or lactating women); ② No severe systemic diseases, no immunodeficiency or autoimmune diseases; ③ No active allergic diseases; ④ No highly sensitive constitution; ⑤ No hormone drugs or immunosuppressants in the past month; ⑥ No participation in other clinical trials at the test site now or in the past three months;

[0062] Termination and exclusion criteria: ① The volunteer requests to terminate the trial due to personal reasons; ② The volunteer has adverse reactions and cannot continue the trial; ③ The volunteer has poor compliance, such as using other skin care products that may affect the trial during the test, etc.

[0063] (2) Data testing:

[0064] Thirty volunteers were selected, and the test was conducted according to the random double-blind principle. The skin with more stratum corneum around the left or right elbow was randomly selected as the test area. The test area was positioned, and the positioning mark was kept on the test area at all times. During the test, no other shower gel or cosmetics or other products that may affect the test results were used on the test area. The volunteers in the experimental group applied the diluted water-soluble azelaic acid system to the same position for 14 consecutive days, once in the morning and once in the evening every day. The volunteers in the control group were not allowed to use other cosmetics or bath products with exfoliating effect during the trial.

[0065] The control group and experimental group volunteers were tested for the number of stratum corneum exfoliation (SEsc) on the 0th, 7th and 14th days, respectively. The test area was kept dry one hour before each test. During the test, the subjects were required to sit quietly for at least 20 minutes in a constant temperature and humidity environment (20-22°C, relative humidity 40%-60%). The measurement personnel measured the number of stratum corneum exfoliation (SEsc) values ​​of the subjects in a fixed area, and each measurement area was measured 3 times to take the average value. The smaller the number of stratum corneum exfoliation (SEsc) value, the less stratum corneum there is in the test area, and the better the exfoliation effect.

[0066] 4. High and low temperature cycle test:

[0067] The water-soluble azelaic acid system was frozen at -5°C and then placed at 40°C to dissolve. This was one cycle and then repeated. It was observed that the state after each dissolution could maintain a stable uniform liquid state without solid precipitation. The example is the data of 15 cycles.

[0068] The raw materials used in the examples are:

[0069] Azelaic acid: particle size 500nm-100μm, particle size has no effect, the particle size selected in the embodiment and comparative example is 30μm, commercially available;

[0070] Panthenol: D-panthenol or DL-panthenol, both of which can be used in the examples and comparative examples, are commercially available;

[0071] Sphingomonas fermentation extract: purchased from Shanghai Youshi Industrial Co., Ltd.;

[0072] Polyacryloyldimethyltaurate: 99%, purchased from Wuhan Lvjing Fenghua Biotechnology Co., Ltd.;

[0073] White willow bark extract: purchased from Xi'an Green Sky Biotechnology Co., Ltd.;

[0074] EDTA2 sodium: 99%, purchased from Shanghai Yuanye Biotechnology Co., Ltd.;

[0075] Portulaca oleracea extract: purchased from Shanghai Huiwen Biotechnology Co., Ltd.;

[0076] % mentioned in the Examples and Comparative Examples without any specific meaning is mass percentage.

[0077] Example 1

[0078] A method for preparing a water-soluble azelaic acid system comprises the following steps:

[0079] Weigh 0.01 mol of azelaic acid, 0.015 mol of salicylic acid and 0.02 mol of DL-panthenol, stir evenly and place in a sealed reaction container. Place the reaction container in an argon protective atmosphere, keep the reaction container stirring and heating at 600 rpm and 95°C for 3 hours, then cool the reaction container to room temperature, so that azelaic acid, salicylic acid and panthenol form a liquid organic body through intermolecular hydrogen bonds, i.e., a water-soluble azelaic acid system.

[0080] The water-soluble azelaic acid system is uniform and transparent;

[0081] The azelaic acid content in the water-soluble azelaic acid system is 23 wt %, and the pH value measured by a pH meter is 4.37;

[0082] The water-soluble azelaic acid system was diluted with water until the azelaic acid accounted for 3% of the total mass fraction, and the system was still homogeneous and transparent;

[0083] The water-soluble azelaic acid system and the diluted system were subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times), and finally both systems were able to maintain a stable and uniform liquid state without phase separation or solid precipitation.

[0084] After the obtained water-soluble azelaic acid system was placed at room temperature for 24 hours, a sample was taken and analyzed and characterized using an infrared spectrometer and a TGA thermogravimetric analyzer. The results are as follows:

[0085] Figure 1 This is the infrared spectrum of the water-soluble azelaic acid system. Figure 1 It can be seen that: in Example 1, 3500-3200 cm -1 The absorption peak in the range of 3355 cm corresponds to the absorption peak of hydroxyl group (hydrogen bond). Compared with a single molecule, the peak in Example 1 moves toward the low wave number direction, from 3355 cm -1 Move to 3340cm -1 This indicates that a strong interaction occurs in the system and a large number of hydrogen bonds are formed. In addition, the newly added position of the water-soluble azelaic acid system in Example 1 is 1746 cm -1 The carbonyl peaks of the three single carbonyl molecules are at 1650-1700 cm -1 The peak of α-hydroxy-1-nitropropene moved to a higher wave number. The reason for this is that the system produced a large amount of hydrogen, which caused the carbonyl electron cloud density to change. The above results all confirm that azelaic acid, salicylic acid, and panthenol form a supramolecular system through intermolecular hydrogen bonds.

[0086] Figure 2 This is the thermogravimetric analysis curve of the water-soluble azelaic acid system. Figure 2 It can be seen that the initial weight loss temperature of the water-soluble azelaic acid system in Example 1 is lower than that of the three monomer components. At the same time, the weight loss trend of the water-soluble azelaic acid system in Example 1 is slower than that of the three monomer components, which also indirectly indicates that the three form an organic whole through hydrogen bonds.

[0087] After the obtained water-soluble azelaic acid system was placed at room temperature for 24 hours, water was added to the water-soluble azelaic acid system to dilute it to a 1% azelaic acid concentration and then the exfoliation efficacy was evaluated. The results are shown in Table 1:

[0088] Table 1

[0089]

[0090] As can be seen from Table 1, compared with the control group, the number of stratum corneum exfoliation (SEsc) of volunteers using the water-soluble azelaic acid system obtained in Example 1 was reduced, and the number of stratum corneum exfoliation (SEsc) was reduced by 22.5% after 14 days. This shows that the water-soluble azelaic acid system has a good effect of reducing stratum corneum exfoliation.

[0091] Example 2

[0092] A method for preparing a water-soluble azelaic acid system comprises the following steps:

[0093] Weigh 0.01 mol of azelaic acid, 0.01 mol of salicylic acid and 0.04 mol of D-panthenol, stir evenly and place in a sealed reaction container. Place the reaction container in a natural air atmosphere, keep the reaction container stirring and heating at 500 rpm and 85°C for 2 hours, then cool the reaction container to room temperature, so that azelaic acid, salicylic acid and panthenol form a liquid organic body through intermolecular hydrogen bonds, i.e., a water-soluble azelaic acid system.

[0094] The water-soluble azelaic acid system is uniform and transparent;

[0095] The azelaic acid content in the water-soluble azelaic acid system is 16 wt %, and the pH value measured by a pH meter is 5.03;

[0096] The water-soluble azelaic acid system was diluted with water until the azelaic acid accounted for 2% of the total mass fraction, and the system was still homogeneous and transparent;

[0097] The water-soluble azelaic acid system and the diluted system were subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times), and finally both systems were able to maintain a stable and uniform liquid state without phase separation or solid precipitation.

[0098] The obtained water-soluble azelaic acid system was placed at room temperature for 24 hours, and then water was added to the water-soluble azelaic acid system to dilute it to a 1% azelaic acid concentration and then the exfoliation efficacy was evaluated. The results are as follows:

[0099] As can be seen from Table 2, compared with the control group, the number of stratum corneum exfoliation (SEsc) of volunteers using the water-soluble azelaic acid system obtained in Example 2 was reduced, and the number of stratum corneum exfoliation (SEsc) after 14 days was reduced by 19.3%. This shows that the water-soluble azelaic acid system has a good effect in reducing stratum corneum exfoliation.

[0100] Table 2

[0101]

[0102] Example 3

[0103] A method for preparing a water-soluble azelaic acid system comprises the following steps:

[0104] Weigh 0.01 mol of azelaic acid, 0.03 mol of salicylic acid, and 0.05 mol of D-panthenol, stir evenly, and place in a sealed reaction container. Place the reaction container in a carbon dioxide atmosphere, keep the reaction container stirring and heating at 700 rpm and 100°C for 4 hours, then cool the reaction container to room temperature, so that azelaic acid, salicylic acid, and panthenol form a liquid organic body through intermolecular hydrogen bonds, that is, a water-soluble azelaic acid system.

[0105] The water-soluble azelaic acid system is uniform and transparent;

[0106] The azelaic acid content in the water-soluble azelaic acid system is 11.5 wt %, and the pH value measured by a pH meter is 3.43;

[0107] The water-soluble azelaic acid system was diluted with water until the azelaic acid accounted for 1% of the total mass fraction, and the system was still homogeneous and transparent;

[0108] The water-soluble azelaic acid system and the diluted system were subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times), and finally both systems were able to maintain a stable and uniform liquid state without phase separation or solid precipitation.

[0109] The obtained water-soluble azelaic acid system was placed at room temperature for 24 hours, and then water was added to the water-soluble azelaic acid system to dilute it to a 1% azelaic acid concentration and then the exfoliation efficacy was evaluated. The results are as follows:

[0110] Table 3 shows the results of the exfoliation efficacy evaluation test. As can be seen from Table 3, compared with the control group, the number of stratum corneum exfoliation (SEsc) of the volunteers using the water-soluble azelaic acid system obtained in Example 3 was reduced, and the number of stratum corneum exfoliation (SEsc) was reduced by 27.0% after 14 days. This shows that the water-soluble azelaic acid system has a good effect in reducing stratum corneum exfoliation.

[0111] Table 3

[0112]

[0113] Comparative Example 1

[0114] The DL-panthenol in Example 1 was omitted, and the other steps were the same as in Example 1 to obtain the product.

[0115] turn out:

[0116] Compared with Example 1, only salicylic acid was selected as a single compatibility component to attempt a water-soluble azelaic acid system, but a uniform, transparent, and stable liquid system could not be obtained;

[0117] The system after being placed at room temperature for 24 hours is a solid-liquid mixture;

[0118] After being placed at room temperature for 24 hours, the solid-liquid mixed system was diluted with water until azelaic acid accounted for 5% of the total mass fraction. A uniform transparent aqueous solution could not be obtained, phase separation occurred, and solids were precipitated.

[0119] Comparative Example 2

[0120] The salicylic acid in Example 1 was omitted, and the other parts were kept the same as in Example 1 to obtain the product.

[0121] turn out:

[0122] Compared with Example 1, the water-soluble azelaic acid system prepared by selecting only panthenol as a single compatibility ingredient is uniform and transparent;

[0123] The water-soluble azelaic acid system was diluted with water until the azelaic acid accounted for 5% of the total mass fraction, and the system was still homogeneous and transparent;

[0124] The water-soluble azelaic acid system and the diluted system were subjected to high and low temperature cycle tests (15 cycles of storage at -5°C and 40°C). In the end, both systems were able to maintain a stable uniform liquid state without phase separation or solid precipitation.

[0125] The obtained water-soluble azelaic acid system was placed at room temperature for 24 hours, and then diluted with water to a 1% azelaic acid concentration for exfoliation efficacy evaluation. The results are as follows:

[0126] It can be seen from Table 4 that after the experimental group used the aqueous solution of the comparative sample for 14 days, the number of stratum corneum exfoliation (SEsc) was slightly improved, and the number of stratum corneum exfoliation (SEsc) decreased by 4.6%. Compared with the results of Example 1, the number of stratum corneum exfoliation was less, and the exfoliation effect was significantly lower than the water-soluble azelaic acid system of Example 1. This shows that in the water-soluble azelaic acid system of Example 1, salicylic acid synergistically enhances the exfoliation effect of the system.

[0127] Table 4

[0128]

[0129] Comparative Example 3

[0130] The amount of salicylic acid in Example 1 was adjusted to 0.16 mol, and the other ingredients were kept consistent with Example 1 to obtain the product.

[0131] turn out:

[0132] Compared with Example 1, only increasing the amount of salicylic acid does not result in a uniform, transparent, and stable liquid system.

[0133] The system after being placed at room temperature for 24 hours is a solid-liquid mixture;

[0134] After being placed at room temperature for 24 hours, the solid-liquid mixed system was diluted with water until azelaic acid accounted for 5% of the total mass fraction. A uniform transparent aqueous solution could not be obtained, phase separation occurred, and solids were precipitated.

[0135] Comparative Example 4

[0136] The amount of azelaic acid in Example 1 was adjusted to 0.06 mol, and the other ingredients were kept consistent with Example 1 to obtain the product.

[0137] turn out:

[0138] Compared with Example 1, only increasing the amount of azelaic acid does not result in a uniform, transparent, and stable liquid system.

[0139] The system after being placed at room temperature for 24 hours is a solid-liquid mixture;

[0140] After being placed at room temperature for 24 hours, the solid-liquid mixed system was diluted with water until azelaic acid accounted for 5% of the total mass fraction. A uniform transparent aqueous solution could not be obtained, phase separation occurred, and solids were precipitated.

[0141] Comparative Example 5

[0142] The heating temperature in Example 1 was adjusted to 55° C., and the other conditions were kept consistent with Example 1 to obtain a product.

[0143] turn out:

[0144] Compared with Example 1, only lowering the heating temperature cannot obtain a uniform, transparent, and stable liquid system;

[0145] The system after being placed at room temperature for 24 hours is a solid-liquid mixture;

[0146] After being placed at room temperature for 24 hours, the solid-liquid mixed system was diluted with water until azelaic acid accounted for 5% of the total mass fraction. A uniform transparent aqueous solution could not be obtained, phase separation occurred, and solids were precipitated.

[0147] Comparative Example 6

[0148] The heating temperature in Example 1 was adjusted to 115° C., and the other conditions were kept consistent with Example 1 to obtain a product.

[0149] turn out:

[0150] Compared with Example 1, only increasing the heating temperature cannot obtain a uniform, transparent, and stable liquid system;

[0151] The system after being placed at room temperature for 24 hours is a solid-liquid mixture;

[0152] After being placed at room temperature for 24 hours, the solid-liquid mixed system was diluted with water until azelaic acid accounted for 5% of the total mass fraction. A uniform transparent aqueous solution could not be obtained, phase separation occurred, and solids were precipitated.

[0153] Comparative Example 7

[0154] The heating time in Example 1 was adjusted to 45 min, and the other conditions were kept consistent with Example 1 to obtain the product.

[0155] turn out:

[0156] Compared with Example 1, only shortening the heating time cannot obtain a uniform, transparent, and stable liquid system;

[0157] The system after being placed at room temperature for 24 hours is a solid-liquid mixture;

[0158] After being placed at room temperature for 24 hours, the solid-liquid mixed system was diluted with water until azelaic acid accounted for 5% of the total mass fraction. A uniform transparent aqueous solution could not be obtained, phase separation occurred, and solids were precipitated.

[0159] Comparative Example 8

[0160] The salicylic acid in Example 1 was replaced with creatinine, and the other parts were kept the same as in Example 1 to obtain the product.

[0161] turn out:

[0162] Compared with Example 1, only one of the system compatibility components was changed, and creatinine was used to replace salicylic acid, but a uniform, transparent and stable liquid system could not be obtained;

[0163] After being placed at room temperature for 24 h, the systems were all solid-liquid mixtures;

[0164] After the solid-liquid mixture was left at room temperature for 24 hours, water was added to dilute the system until azelaic acid accounted for 5% of the total mass fraction. However, a uniform transparent aqueous solution could not be obtained, and phase separation occurred with solid precipitation.

[0165] Comparative Example 9

[0166] The panthenol in Example 1 was adjusted to be replaced by polyethylene glycol 400, glycerol or propylene glycol, and the other parts were kept the same as in Example 1 to obtain a product.

[0167] turn out:

[0168] Compared with Example 1, only one of the system compatibility components was changed, and polyethylene glycol 400, glycerin or propylene glycol were used to replace panthenol, but a uniform, transparent and stable liquid system could not be obtained;

[0169] After being placed at room temperature for 24 h, the systems were all solid-liquid mixtures;

[0170] After the solid-liquid mixture was left at room temperature for 24 hours, water was added to dilute the system until azelaic acid accounted for 5% of the total mass fraction. However, a uniform transparent aqueous solution could not be obtained, and phase separation occurred with solid precipitation.

[0171] Comparative Example 10

[0172] The panthenol in Example 1 was replaced by a mixture of polyethylene glycol and propylene glycol (mass ratio of 3:1), and the other ingredients were kept the same as in Example 1 to obtain a product.

[0173] turn out:

[0174] Compared with Example 1, only one of the system compatibility components was changed, and a mixture of polyethylene glycol and propylene glycol was used to replace panthenol, but a uniform, transparent and stable liquid system could not be obtained;

[0175] The system after being placed at room temperature for 24 hours is a solid-liquid mixture;

[0176] After being placed at room temperature for 24 hours, the solid-liquid mixed system was diluted with water until azelaic acid accounted for 5% of the total mass fraction. A uniform transparent aqueous solution could not be obtained, phase separation occurred, and solids were precipitated.

[0177] Comparative Example 11

[0178] The salicylic acid in Example 1 is adjusted to be replaced by mandelic acid or phenyl salicylate, and the other steps are kept consistent with Example 1 to obtain the product.

[0179] turn out:

[0180] Compared with Example 1, only one of the system compatibility components was changed, and mandelic acid or phenyl salicylate was used to replace salicylic acid, but a uniform, transparent and stable liquid system could not be obtained;

[0181] After being placed at room temperature for 24 h, the systems were all solid-liquid mixtures;

[0182] After the solid-liquid mixture was left at room temperature for 24 hours, water was added to dilute the system until azelaic acid accounted for 5% of the total mass fraction. However, a uniform transparent aqueous solution could not be obtained, and phase separation occurred with solid precipitation.

[0183] Example 4 Application in cosmetics

[0184] The soluble azelaic acid supramolecular combination system prepared in Example 1 is used in the preparation of cosmetics, specifically as follows:

[0185] The essence comprises the following components in percentage by mass: 3% glycerol, 3% butylene glycol, 0.4% phenoxyethanol, 0.4% caprylyl glycol, 0.1% sphingomonas fermentation extract, 0.05% sodium hyaluronate, 0.1% polyacryloyldimethyl taurate, 20% soluble azelaic acid supramolecular combination system of Example 1, 2% white willow bark extract, 0.05% sodium EDTA2, 2% purslane extract, and the rest is water;

[0186] The preparation method of the essence is as follows:

[0187] Add water, glycerin, butylene glycol, phenoxyethanol, caprylyl glycol and sodium EDTA2 into the main cup and dissolve evenly, then heat to 75°C;

[0188] Then add Sphingomonas fermentation extract, sodium hyaluronate, and polyacryloyldimethyl taurate into the main cup and stir evenly.

[0189] The temperature was lowered to 45° C., and the soluble azelaic acid supramolecular combination system of Example 1, white willow bark extract, and purslane extract were added, and stirred evenly to complete the preparation.

[0190] 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.

[0191] Comparative Example 12

[0192] The soluble azelaic acid supramolecular combination system in Example 4 was adjusted to 4.68% w / w azelaic acid, 5.14% w / w salicylic acid, and 10.18% w / w panthenol, and the rest was kept consistent with Example 4 to obtain an essence.

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

[0194] 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 a water-soluble azelaic acid system, characterized in that: The steps include: Mix azelaic acid, salicylic acid and panthenol evenly, and heat with stirring at 65-110°C for 1-8 hours, so that azelaic acid, salicylic acid and panthenol form a liquid organic body through intermolecular hydrogen bonds, i.e., a water-soluble azelaic acid system; Among them, the molar ratio of azelaic acid, salicylic acid and panthenol is 1:0.3~15:1~12.

2. The method according to claim 1, characterized in that The rotation speed of stirring and heating is 300~1000rpm; the atmosphere of stirring and heating is air, argon or carbon dioxide.

3. The water-soluble azelaic acid system prepared by the method according to claim 1 or 2.

4. Use of the water-soluble azelaic acid system according to claim 3 in the preparation of medicines.

5. A drug, characterized in that It contains the water-soluble azelaic acid system as described in claim 3.

6. A method for synergistically improving the water solubility of azelaic acid by using salicylic acid and panthenol, characterized in that: The steps include: Mix azelaic acid, salicylic acid and panthenol evenly, and heat with stirring at 65-110°C for 1-8 hours, so that azelaic acid, salicylic acid and panthenol form a liquid organic body through intermolecular hydrogen bonds, i.e., a water-soluble azelaic acid system; Among them, the molar ratio of azelaic acid, salicylic acid and panthenol is 1:0.3~15:1~12.

Images