A soluble azelaic acid supramolecular combination system with soothing effect

Abstract

The present invention discloses a soluble azelaic acid supramolecular combination system with soothing effect, belonging to the field of supramolecular technology. The preparation method of the soluble azelaic acid supramolecular combination system with soothing effect in the present invention comprises the following steps: mixing azelaic acid, ectoine and panthenol in a molar ratio of 1:0.2-3:1-10, heating at 70-110°C for 2-16h in an atmosphere of nitrogen, argon or air, so that azelaic acid, ectoine and panthenol form supramolecular through hydrogen bonds, and thus a soluble azelaic acid supramolecular combination system with soothing effect is obtained. The maximum content of azelaic acid in the soluble azelaic acid supramolecular combination system prepared by the present invention can reach 45%, and the soluble azelaic acid supramolecular combination system has high solubility and stability in water, and a large amount of water is added to the system to keep the system stable, so that the mass concentration of azelaic acid in the aqueous solution can be 0.3%-35% without precipitation.

Description

Technical Field

[0001] The invention relates to a soluble azelaic acid supramolecular combination system with soothing effect, belonging to the technical field of supramolecular. Background Art

[0002] Azelaic Acid is a common ingredient in cosmetics with a variety of uses and benefits; it performs well in conditioning the skin, especially for the care of acne and acne-prone skin. Azelaic Acid has antibacterial and anti-inflammatory effects, which can reduce the formation of acne and relieve skin problems related to inflammation. In addition, Azelaic Acid can also regulate sebum secretion and reduce the accumulation of oil on the surface of the skin, thereby improving the condition of oily and combination skin; it also has a slight keratin conditioning effect, which can help reduce keratin accumulation and make the skin more soft and smooth.

[0003] However, the properties of azelaic acid itself limit its use in cosmetic formulations. Specifically, the solubility of azelaic acid in water is low (2.4 g / L), so most existing dosage forms use emulsification technology to make it into creams. Even so, the low solubility greatly reduces its bioavailability, which means that 15-20% of azelaic acid must be used in these formulations to achieve the desired effect. High concentrations of azelaic acid may increase the irritation of the product, so its concentration needs to be carefully balanced in the formulation design to ensure the safety and tolerability of the product.

[0004] It can be seen that improving the water solubility of azelaic acid has very important application value.

[0005] At present, some researchers have used some methods to improve the water solubility of azelaic acid, as follows:

[0006] Patent CN 113248364 A 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;

[0007] Patent CN 112624918 A 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 108187070 A 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] Patent CN 110669226 A discloses a method for preparing a polyethylene glycol / propylene glycol / azelaic acid supramolecular system, in which 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; propylene glycol and polyethylene glycol are commonly used solvents and solubilizers in cosmetic formulas, and this method is essentially the thermal dissolution of azelaic acid in the presence of conventional alcohol and polyethylene glycol solubilization, so the solubility of azelaic acid can only be increased by a maximum of 3.33 times, or about 8 g / L. Summary of the invention

[0010] [Technical issues]

[0011] Azelaic acid has poor water solubility, so its usage in cream-like cosmetics and pharmaceutical ointments is high, reaching 15-20%. However, even if it is made into a cream, its bioavailability is still very low;

[0012] The current methods for improving the water solubility of azelaic acid do not significantly improve its solubility.

[0013] [Technical solution]

[0014] In order to solve the above problems, the present invention combines azelaic acid, ectoine and panthenol through supramolecular technology based on the interaction between hydrogen bond donors and hydrogen bond acceptors in the supramolecular system, thereby solving the problem of low solubility of azelaic acid; at the same time, the supramolecular synergistic effect is used to reduce the irritation of azelaic acid. Compared with the prior art, the present invention is simple and easy to operate, suitable for large-scale production, and has broad application prospects in the fields of pharmaceutical science, daily chemicals or food science.

[0015] Supramolecular usually refers to two or more molecules combined by intermolecular interactions to form complex, organized aggregates. When using supramolecular systems to improve the solubility of azelaic acid, it is very important to choose the right compatible molecules. The type and amount of compatible molecules will directly affect the ratio of hydrogen bond donors and hydrogen bond acceptors in the supramolecular system, and thus determine whether the supramolecular system can be formed.

[0016] Ectoine is a natural active ingredient that soothes, protects and repairs the skin. In terms of skin protection, Ectoine can form a protective film on the skin surface, effectively blocking the invasion of harmful substances and irritating factors in the environment on the skin, and reducing the damage to the skin by external factors. Moreover, it also has anti-inflammatory and skin soothing effects, and can reduce skin redness, swelling, itching and other discomforts.

[0017] Panthenol is a vitamin B5 derivative that can promote the metabolism of proteins, lipids, and carbohydrates in the human body. It can also act as a deep-penetrating moisturizer, stimulate the growth of epithelial cells, promote wound healing, and have an anti-inflammatory effect.

[0018] The first object of the present invention is to provide a method for preparing a soluble azelaic acid supramolecular combination system having a soothing effect, comprising the following steps:

[0019] Mixing azelaic acid, ectoine and panthenol and heating them allows azelaic acid, ectoine and panthenol to form supramolecules through hydrogen bonds, thereby obtaining a soluble azelaic acid supramolecule combination system with soothing effects.

[0020] In one embodiment, the molar ratio of azelaic acid, ectoine and panthenol is 1:0.2-3:1-10, more preferably 1:0.2-2:1-8, and even more preferably 1:0.5-1:1-5.

[0021] In one embodiment, the mixed heating atmosphere is nitrogen, argon or air.

[0022] In one embodiment, the mixing and heating is carried out in a closed container.

[0023] In one embodiment, the temperature of the mixed heating is 70-110°C, more preferably 80-110°C, and even more preferably 90-105°C.

[0024] In one embodiment, the mixing and heating time is 2-16 hours, more preferably 3-10 hours, and even more preferably 4-8 hours.

[0025] The second objective of the present invention is to obtain a soluble azelaic acid supramolecular combination system having soothing effect prepared by the method described in the present invention.

[0026] In one embodiment, the soluble azelaic acid supramolecular combination system having soothing effect is in liquid form.

[0027] In one embodiment, the maximum content (by mass) of azelaic acid in the soluble azelaic acid supramolecular combination system having soothing effect can reach 45%.

[0028] In one embodiment, the soluble azelaic acid supramolecular combination system having soothing effect has high solubility and stability in water, so that the mass concentration of azelaic acid in the aqueous solution is 0.3%-35% without precipitation.

[0029] In one embodiment, the soluble azelaic acid supramolecular combination system with soothing effect is formed by intermolecular hydrogen bonds, which does not change the molecular structures of azelaic acid, ectoine, and panthenol.

[0030] In one embodiment, the soluble azelaic acid supramolecular combination system with soothing effect uses ectoine as a system compatibility component to increase the water solubility of azelaic acid, while effectively and synergistically enhancing the soothing effect of the combination.

[0031] The third objective of the present invention is to apply the soluble azelaic acid supramolecular combination system with soothing effect described in the present invention in the fields of pharmaceutical science, daily chemicals or food science.

[0032] The fourth object of the present invention is to provide a cosmetic comprising the soluble azelaic acid supramolecular combination system having soothing effect as described in the present invention.

[0033] In one embodiment, the addition amount of the soluble azelaic acid supramolecular combination system having soothing effect is 0.1-45% (mass percentage).

[0034] In one embodiment, the cosmetics include essence, essence water, spray, skin care foam, lotion, shampoo, etc.

[0035] The fifth object of the present invention is to provide a medicine for treating acne skin, which adopts the soluble azelaic acid supramolecular combination system with soothing effect described in the present invention.

[0036] In one embodiment, the addition amount of the soluble azelaic acid supramolecular combination system having soothing effect is 0.1-45% (mass percentage).

[0037] In one embodiment, the acne treatment drug is a gel, a spray, a liquid medicine, a cream, etc.

[0038] The sixth object of the present invention is to provide a food preservative, which uses the soluble azelaic acid supramolecular combination system with soothing effect described in the present invention.

[0039] In one embodiment, the addition amount of the soluble azelaic acid supramolecular combination system having soothing effect is 0.1-45% (mass percentage).

[0040] The sixth object of the present invention is to provide a mouthwash, which uses the soluble azelaic acid supramolecular combination system with soothing effect described in the present invention.

[0041] In one embodiment, the addition amount of the soluble azelaic acid supramolecular combination system having soothing effect is 0.1-45% (mass percentage).

[0042] A seventh object of the present invention is to provide a method for increasing the solubility of azelaic acid in water, comprising the following steps:

[0043] Azelaic acid, ectoine and panthenol are mixed and heated, so that azelaic acid, ectoine and panthenol form supramolecules through hydrogen bonds, thereby obtaining a soluble azelaic acid supramolecule combination system.

[0044] [Beneficial Effects]

[0045] (1) The present invention uses intermolecular hydrogen bonds to allow azelaic acid, ectoine, and panthenol to interact with each other to form a liquid-soluble azelaic acid supramolecular combination system; the maximum content of azelaic acid in the system can reach 45% (mass percentage), and the soluble azelaic acid supramolecular combination system has high solubility and stability in water; the system can still be kept stable by adding a large amount of water, and the mass concentration of azelaic acid in the aqueous solution can be kept at 0.3%-35% without precipitation, thereby greatly improving the water solubility of azelaic acid.

[0046] (2) The soluble azelaic acid supramolecular combination system prepared by the present invention selects ectoine as one of the system's compatible components, which increases the water solubility and stability of azelaic acid while effectively reducing the irritation of azelaic acid, achieving a synergistic effect of soothing and repairing, greatly enhancing the competitiveness of azelaic acid in cosmetic applications and formula design, and broadening its application scenarios.

[0047] (3) The preparation process of the present invention is simple, does not require raw material pretreatment and separation and purification, and the process is green and environmentally friendly, without the use of organic solvents and the generation of toxic and harmful substances.

[0048] (4) The soluble azelaic acid supramolecular combination system prepared by the present invention can be used directly or as a raw material in the fields of pharmaceutical science, daily chemicals or food science. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 This is the infrared spectrum of the soluble azelaic acid supramolecular combination system of Example 1.

[0050] Figure 2 This is the thermogravimetric analysis curve of the soluble azelaic acid supramolecular assembly system of Example 1.

[0051] Figure 3The properties of the system products of Examples 1 to 3 and Comparative Examples 1 to 8 after being left for 24 hours. DETAILED DESCRIPTION

[0052] 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.

[0053] Test method:

[0054] 1. Fourier transform infrared spectroscopy test parameters are:

[0055] Machine specifications: FTS6000;

[0056] Machine manufacturer: Bio-ard Company, USA;

[0057] Specific experimental parameters: scanning range is 500-4000cm -1 , resolution 4cm -1 .

[0058] 2. TGA thermogravimetric analyzer test parameters are:

[0059] Machine specifications: Mettler TGA2 SF / 1100;

[0060] Machine manufacturer: Mettler Toledo, Switzerland;

[0061] Specific 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.

[0062] 3. Evaluation of soothing and repairing effects:

[0063] Screening of people aged 20-45 years old, without severe systemic diseases, immunodeficiency or autoimmune diseases, active allergic diseases, no history of severe allergies to cosmetics, and those who have not used hormone drugs and immunosuppressants in the past month. Those who have no scars, pigments, atrophy, port wine stains or other blemishes on the skin test site that affect the determination of the test results, those who have not participated in other clinical tests, use the test substances according to regulations and have complete information, and sign the volunteer informed consent before the test.

[0064] 30 qualified volunteers were screened and the inner side of the arm was selected as the test site. No products (cosmetics or external medicines) could be used on the test site 3 days before the test. The subjects were required to clean the test site with clean water and wipe off the moisture with dry facial tissue.

[0065] The subjects sat quietly for 30 minutes in a constant temperature and humidity environment (temperature (21±1)℃, humidity (40-60)%), and marked two circular areas with a diameter of 18mm on the corresponding positions on the inner side of the left and right forearms respectively. They were not allowed to drink water or beverages during this period. The test site was exposed and placed in the test state, and remained relaxed. First, the basal values ​​of the two areas were measured, and then a closed patch test was performed on the inner side of both forearms with a mass fraction of 1% sodium dodecyl sulfate (SLS) solution for 24 hours to induce erythema. The right hand area was the experimental group;

[0066] The supramolecular combination system was diluted 10 times with water and then applied to the right hand test area. The left hand area was the control group. From the 1st to the 10th day of the experimental group, the subjects used the test product in the morning and evening on the right hand area, and the left hand area as the control group did not use any product.

[0067] Conduct soothing and repairing experimental data test: measure the skin parameter values ​​of the patch sites on the left and right hands on the 1st, 5th and 10th day after using the test product, including the transepidermal water loss (TEWL value) and the red pigment content of the skin. The test of the same subject must be completed by the same tester using the same instrument, and the test probe should be cleaned between two measurements.

[0068] 4. High and low temperature cycle test:

[0069] 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.

[0070] The raw materials used in the embodiment:

[0071] Ecdoin: white powder, purity 99%, commercially available;

[0072] Azelaic acid: particle size 500nm-100μm, particle size has no effect, the particle size selected in the embodiment and comparative example is 20μm, commercially available;

[0073] Panthenol: D-panthenol or DL-panthenol, both of which can be used in the examples and comparative examples, are commercially available;

[0074] Sphingomonas fermentation extract: purchased from Shanghai Youshi Industrial Co., Ltd.;

[0075] Polyacryloyldimethyltaurate: 99%, purchased from Wuhan Lvjing Fenghua Biotechnology Co., Ltd.;

[0076] White willow bark extract: purchased from Xi'an Green Sky Biotechnology Co., Ltd.;

[0077] EDTA2 sodium: 99%, purchased from Shanghai Yuanye Biotechnology Co., Ltd.;

[0078] Portulaca oleracea extract: purchased from Shanghai Huiwen Biotechnology Co., Ltd.;

[0079] % mentioned in the Examples and Comparative Examples without any specific meaning is mass percentage.

[0080] Example 1

[0081] A method for preparing a soluble azelaic acid supramolecular combination system with soothing effect comprises the following steps:

[0082] Weigh 0.01 mol of azelaic acid, 0.008 mol of ectoine and 0.03 mol of D-panthenol, put them into a closed reaction container and mix them evenly. Heat the mixture under a nitrogen atmosphere at 95°C. During this process, azelaic acid, ectoine and panthenol form a supramolecular combination through hydrogen bonds. After 4 hours of treatment, a uniform, transparent liquid soluble azelaic acid supramolecular combination system with soothing effect is obtained.

[0083] The soluble azelaic acid supramolecular combination system with soothing effect contains 20.5% azelaic acid;

[0084] The soluble azelaic acid supramolecular combination system is mixed with water in a specific proportion, so that the mass concentration of azelaic acid in the aqueous solution is 3%, and the system can maintain a stable and uniform liquid state;

[0085] The soluble azelaic acid supramolecular combination system and the diluted liquid system were subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times), and finally the two systems were still able to maintain a stable and uniform transparent liquid system.

[0086] After the soluble azelaic acid supramolecular combination system was placed at room temperature for 24 hours, a sample was taken and the test data were characterized by infrared spectrometer and TGA thermogravimetric analyzer. The results are as follows Figure 1 and Figure 2 :

[0087] from Figure 1 It can be seen that: 3500-3200cm -1 The absorption peak in the range of 1650cm-1 of the soluble azelaic acid supramolecular combination system of Example 1 can be found in the absorption peak of the hydroxyl group (hydrogen bond). However, the peak of the soluble azelaic acid supramolecular combination system of Example 1 is broader and the peak position moves toward the low wave number direction, indicating that a large number of hydrogen bonds are formed in the system; compared with the 1650cm-1 of the single azelaic acid, panthenol, and 1650cm-1 of the soluble azelaic acid supramolecular combination system of Example 1 ... -1 -1700cm -1The stretching vibration of the carbonyl group has a peak, and the soluble azelaic acid supramolecular assembly system of Example 1 has moved and split in the direction of high wavenumber at this peak position. This is due to the generation of a large number of hydrogen bonds within the system, which leads to a change in the electron cloud density of the carbonyl group. The above results all confirm that azelaic acid, ectoine, and panthenol form a supramolecular self-assembly system through intermolecular hydrogen bonds.

[0088] from Figure 2 It can be seen that the initial weight loss temperature of the soluble azelaic acid supramolecular combination system in Example 1 is lower than that of the three monomer components, and is close to the initial weight loss temperature of panthenol. At the same time, the overall weight loss of the soluble azelaic acid supramolecular combination system is slower than that of the three monomer components, which indirectly indicates that the three form an organic whole through hydrogen bonds.

[0089] The soluble azelaic acid supramolecular combination system was diluted ten times with water and then evaluated for soothing and repairing effects. The results are shown in Table 1:

[0090] Table 1

[0091]

[0092] As can be seen from Table 1: The soluble azelaic acid supramolecular combination system obtained in Example 1 has significant differences in epidermal water loss and skin hemoglobin test results (P<0.05). The skin of the experimental group can basically recover after using the soluble azelaic acid supramolecular combination system for 10 days, and the test results are close to the initial value of the test; the control group has a slight recovery after 10 days, but it is still more serious than the initial value of the test, and the recovery is slow. This shows that the soluble azelaic acid supramolecular combination system can repair the skin barrier, improve skin erythema, and has a soothing and repairing effect on damaged skin.

[0093] Example 2

[0094] A method for preparing a soluble azelaic acid supramolecular combination system with soothing effect comprises the following steps:

[0095] Weigh 0.01 mol of azelaic acid, 0.005 mol of ectoine and 0.01 mol of DL-panthenol, put them into a closed reaction container and mix them evenly. Heat the mixture under an argon atmosphere at 90°C. During this process, azelaic acid, ectoine and panthenol form a supramolecular combination through hydrogen bonds. After 8 hours of treatment, a uniform, transparent liquid soluble azelaic acid supramolecular combination system with soothing effect is obtained.

[0096] The soluble azelaic acid supramolecular combination system with soothing effect contains 40% azelaic acid;

[0097] The soluble azelaic acid supramolecular combination system is mixed with water in a specific proportion, so that the mass concentration of azelaic acid in the aqueous solution is 20%, and the system can maintain a stable and uniform liquid state;

[0098] The soluble azelaic acid supramolecular combination system and the diluted liquid system were subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times), and finally the two systems were still able to maintain a stable and uniform transparent liquid system.

[0099] The soluble azelaic acid supramolecular combination system was diluted ten times with water and then evaluated for soothing and repairing effects. The results are shown in Table 2:

[0100] Table 2

[0101]

[0102] As can be seen from Table 2: The soluble azelaic acid supramolecular combination system obtained in Example 2 has significant differences in epidermal water loss and skin hemoglobin test results (P<0.05); the skin of the experimental group can basically recover after using the soluble azelaic acid supramolecular combination system for 10 days, and the test results are close to the initial value of the test; the control group has a slight recovery after 10 days, but it is still more serious than the initial value of the test, and the recovery is slow. This shows that the soluble azelaic acid supramolecular combination system can repair the skin barrier, improve skin erythema, and has a soothing and repairing effect on damaged skin.

[0103] Example 3

[0104] A method for preparing a soluble azelaic acid supramolecular combination system with soothing effect comprises the following steps:

[0105] Weigh 0.01 mol of azelaic acid, 0.01 mol of ectoine and 0.05 mol of DL-panthenol, put them into a closed reaction container and mix them evenly. Heat the mixture in an air atmosphere at 105°C. During this process, azelaic acid, ectoine and panthenol form a supramolecular combination through hydrogen bonds. After 6 hours of treatment, a uniform, transparent liquid soluble azelaic acid supramolecular combination system with soothing effect is obtained.

[0106] The soluble azelaic acid supramolecular combination system with soothing effect contains 14% azelaic acid;

[0107] The soluble azelaic acid supramolecular combination system is mixed with water in a specific proportion, so that the mass concentration of azelaic acid in the aqueous solution is 10%, and the system can maintain a stable and uniform liquid state;

[0108] The soluble azelaic acid supramolecular combination system and the diluted liquid system were subjected to high and low temperature cycle tests (cycled and stored at -5°C and 40°C for 15 times), and finally the two systems were still able to maintain a stable and uniform transparent liquid system.

[0109] The soluble azelaic acid supramolecular combination system was diluted ten times with water and then evaluated for soothing and repairing effects. The results are shown in Table 3:

[0110] As can be seen from Table 3: The soluble azelaic acid supramolecular combination system obtained in Example 3 has significant differences in epidermal water loss and skin hemoglobin test results (P<0.05); the skin of the experimental group can basically recover after using the soluble azelaic acid supramolecular combination system for 10 days, and the test results are close to the initial value of the test; the control group has a slight recovery after 10 days, but it is still more serious than the initial value of the test, and the recovery is slow. This shows that the soluble azelaic acid supramolecular combination system can repair the skin barrier, improve skin erythema, and has a soothing and repairing effect on damaged skin.

[0111] Table 3

[0112]

[0113] Comparative Example 1

[0114] The D-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 selecting ectoine as a single compatible molecule for the supramolecular combination attempt cannot obtain a uniform and transparent liquid system, and the system is a solid-liquid mixture;

[0117] When the system was mixed with water in a specific proportion so that the mass concentration of azelaic acid was 3%, the system still could not maintain a stable and uniform liquid state and a large amount of solid insoluble matter existed.

[0118] Comparative Example 2

[0119] The ectoine in Example 1 was omitted, and the other parts were kept consistent with Example 1 to obtain a product.

[0120] turn out:

[0121] Compared with Example 1, only panthenol was selected as a single compatible molecule for the supramolecular combination attempt, and a uniform, transparent and stable liquid system was obtained;

[0122] The system is mixed with water in a specific proportion so that the mass concentration of azelaic acid is 3%, and the system can still maintain a stable and uniform liquid system;

[0123] The soothing and repairing efficacy of the system product was evaluated (the testing method was the same as in Example 1), and the test results are shown in Table 4.

[0124] It can be seen from Table 4 that the system of Comparative Example 1 has a certain soothing and repairing effect, but its long-term repairing ability is obviously inferior to that of the soluble azelaic acid supramolecular combination system obtained in Example 1.

[0125] Table 4

[0126]

[0127] Comparative Example 3

[0128] The amount of ectoine in Example 1 was adjusted to 0.035 mol, and the other contents were kept consistent with Example 1 to obtain the product.

[0129] turn out:

[0130] Compared with Example 1, only increasing the amount of ectoine added does not result in a uniform and transparent liquid system, and the system is a solid-liquid mixture;

[0131] When the system was mixed with water in a specific proportion so that the mass concentration of azelaic acid was 3%, the system still could not maintain a stable and uniform liquid state and a large amount of solid insoluble matter existed.

[0132] Comparative Example 4

[0133] The amount of azelaic acid in Example 1 was adjusted to 0.045 mol, and the other ingredients were kept consistent with Example 1 to obtain the product.

[0134] turn out:

[0135] Compared with Example 1, only increasing the amount of azelaic acid added does not result in a uniform and transparent liquid system, and the system is a solid-liquid mixture;

[0136] When the system was mixed with water in a specific proportion so that the mass concentration of azelaic acid was 3%, the system still could not maintain a stable and uniform liquid state and a large amount of solid insoluble matter existed.

[0137] Comparative Example 5

[0138] The heating temperature in Example 1 was adjusted to 60° C., and the other conditions were kept consistent with Example 1 to obtain a product.

[0139] turn out:

[0140] Compared with Example 1, only lowering the heating temperature cannot obtain a uniform and transparent liquid system, and the system is a solid-liquid mixture;

[0141] When the system was mixed with water in a specific proportion so that the mass concentration of azelaic acid was 3%, the system still could not maintain a stable and uniform liquid state and a large amount of solid insoluble matter existed.

[0142] Comparative Example 6

[0143] The heating temperature in Example 1 was adjusted to 120° C., and the other conditions were kept consistent with Example 1 to obtain a product.

[0144] turn out:

[0145] Compared with Example 1, a uniform and transparent liquid system can be obtained by simply increasing the heating temperature, but the viscosity of the system increases, a special odor gas is generated, and the color deepens. It is speculated that a chemical reaction may have occurred in the system rather than a hydrogen bond.

[0146] Comparative Example 7

[0147] The heating time in Example 1 was adjusted to 1.5 h, and the other conditions were kept consistent with Example 1 to obtain the product.

[0148] turn out:

[0149] Compared with Example 1, only by shortening the heating time, a uniform and transparent liquid system cannot be obtained, and the system is a solid-liquid mixture;

[0150] When the system was mixed with water in a specific proportion so that the mass concentration of azelaic acid was 3%, the system still could not maintain a stable and uniform liquid state and solid insoluble matter existed.

[0151] Comparative Example 8

[0152] The ectoine in Example 1 is adjusted to zinc gluconate, and the other parts are kept consistent with Example 1 to obtain a product.

[0153] turn out:

[0154] Compared with Example 1, only one of the system compatibility components was changed, that is, zinc gluconate was selected to try to replace ectoine, but a uniform and transparent liquid system could not be obtained, and the system was a solid-liquid mixture;

[0155] When the system was mixed with water in a specific proportion so that the mass concentration of azelaic acid was 3%, the system still could not maintain a stable and uniform liquid state and a large amount of solid insoluble matter existed.

[0156] Comparative Example 9

[0157] The ectoine in Example 1 was adjusted to ceramide, and the other aspects were kept consistent with Example 1 to obtain a product.

[0158] turn out:

[0159] Compared with Example 1, only one of the system components was changed, that is, ceramide was used to replace ectoine, but a uniform and transparent liquid system could not be obtained, and the system was solid;

[0160] When the solid system is mixed with water in a specific proportion so that the mass concentration of azelaic acid is 3%, the system still cannot maintain a stable and uniform liquid state and a large amount of solid insoluble matter exists.

[0161] Comparative Example 10

[0162] The ectoine in Example 1 is adjusted to hydroxyectoine, and the rest is kept consistent with Example 1 to obtain a product.

[0163] turn out:

[0164] Compared with Example 1, only one of the system's compatible components was changed, that is, hydroxyectoine was used to try to replace ectoine, but a uniform and transparent liquid system could not be obtained, and the system was a solid-liquid mixture;

[0165] When the system was mixed with water in a specific proportion so that the mass concentration of azelaic acid was 3%, the system still could not maintain a stable and uniform liquid state and a large amount of solid insoluble matter existed.

[0166] Comparative Example 11

[0167] The panthenol in Example 1 was adjusted to polyethylene glycol 400, and the other contents were kept the same as in Example 1 to obtain the product.

[0168] turn out:

[0169] Compared with Example 1, only one of the system components was changed, that is, polyethylene glycol 400 was used to try to replace panthenol, but a uniform and transparent liquid system could not be obtained, and the system was a solid-liquid mixture;

[0170] When the system was mixed with water in a specific proportion so that the mass concentration of azelaic acid was 3%, the system still could not maintain a stable and uniform liquid state and a large amount of solid insoluble matter existed.

[0171] Comparative Example 12

[0172] The panthenol in Example 1 was adjusted to propylene glycol, and the other parts 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's ingredients was changed, that is, propylene glycol was used to replace panthenol, but a uniform and transparent liquid system could not be obtained, and the system was a solid-liquid mixture;

[0175] When the system was mixed with water in a specific proportion so that the mass concentration of azelaic acid was 3%, the system still could not maintain a stable and uniform liquid state and a large amount of solid insoluble matter existed.

[0176] Comparative Example 13

[0177] The 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.

[0178] turn out:

[0179] Compared with Example 1, only one of the system components was changed, that is, a mixture of polyethylene glycol 400 and propylene glycol was used to replace panthenol, but a uniform and transparent liquid system could not be obtained, and the system was a solid-liquid mixture;

[0180] When the system was mixed with water in a specific proportion so that the mass concentration of azelaic acid was 3%, the system still could not maintain a stable and uniform liquid state and a large amount of solid insoluble matter existed.

[0181] Comparative Example 14

[0182] The panthenol in Example 1 was adjusted to glycerol, and the other conditions were the same as in Example 1 to obtain a product.

[0183] turn out:

[0184] Compared with Example 1, only one of the system's ingredients was changed, i.e., glycerol was used to replace panthenol, but a uniform and transparent liquid system could not be obtained, and the system was a solid-liquid mixture;

[0185] When the system was mixed with water in a specific proportion so that the mass concentration of azelaic acid was 3%, the system still could not maintain a stable and uniform liquid state and a large amount of solid insoluble matter existed.

[0186] Example 4 Application in cosmetics

[0187] The soluble azelaic acid supramolecular combination system prepared in Example 1 is used in the preparation of cosmetics, specifically as follows:

[0188] Add ingredients 1-5 and 11 into the main cup and dissolve evenly, then heat to 75℃;

[0189] Add ingredients 6-8 into the main cup and stir well;

[0190] Cool down to 45℃, add raw materials No. 9, 10 and 12, stir evenly, and the preparation is complete.

[0191] 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.

[0192] Table 5 Essence formula

[0193] Serial number Raw material name %w / w 1 water To 100 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 Supramolecular assembly system 20 10 White Willow Bark Extract 2 11 Sodium EDTA2 0.05 12 Purslane Extract 2

[0194] Comparative Example 15

[0195] According to the formula of the essence in Table 5, the soluble azelaic acid supramolecular combination system of Example 1 was replaced with 4.1% w / w azelaic acid, 2.48% w / w ectoine, and 13.42% w / w D-panthenol to prepare the essence as shown in Table 6 below;

[0196] The preparation process is:

[0197] Add ingredients 1-5 and 13 into the main cup and dissolve evenly, then heat to 75℃;

[0198] Add ingredients 6-8 into the main cup and stir well;

[0199] Cool down to 45℃, add raw materials No. 9-12 and 14, stir evenly, and the preparation is complete.

[0200] The stability of the essence was tested according to GB / T 26367-2010 standard and the stability was unqualified with solid precipitation.

[0201] Table 6 Essence formula

[0202] Serial number Raw material name %w / w 1 water To 100 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 4.1 10 Ekdoin 2.48 11 D-Panthenol 13.42 12 White Willow Bark Extract 2 13 Sodium EDTA2 0.05 14 Purslane Extract 2

[0203] 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 soluble azelaic acid supramolecular combination system with soothing effect, characterized in that: The steps include: Mixing azelaic acid, ectoine and panthenol and heating them, so that azelaic acid, ectoine and panthenol form supramolecules through hydrogen bonds, thus obtaining a soluble azelaic acid supramolecule combination system with soothing effects; Wherein, the molar ratio of azelaic acid, ectoine and panthenol is 1:0.2-3:1-10; The temperature of the mixed heating is 70-110°C and the time is 2-16h.

2. The preparation method according to claim 1, characterized in that: The mixed heating atmosphere is nitrogen, argon or air.

3. The soluble azelaic acid supramolecular combination system with soothing effect prepared by the preparation method according to claim 1 or 2.

4. Use of the soluble azelaic acid supramolecular combination system with soothing effect as claimed in claim 3 in the preparation of medicines or daily chemical products.

5. A cosmetic, characterized in that: It contains the soluble azelaic acid supramolecular combination system with soothing effect as described in claim 3.

6. A drug for treating acne, characterized in that: It contains the soluble azelaic acid supramolecular combination system with soothing effect as described in claim 3.

7. A saliva water, characterized in that: It contains the soluble azelaic acid supramolecular combination system with soothing effect as described in claim 3.

8. A method for increasing the solubility of azelaic acid in water, characterized in that: The steps include: Mixing and heating azelaic acid, ectoine and panthenol, so that azelaic acid, ectoine and panthenol form supramolecules through hydrogen bonds, thereby obtaining a soluble azelaic acid supramolecule combination system; Wherein, the molar ratio of azelaic acid, ectoine and panthenol is 1:0.2-3:1-10; The temperature of the mixed heating is 70-110°C and the time is 2-16h.

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