Azelaic acid gel containing coptis chinensis as well as preparation method and application of azelaic acid gel

Abstract

The invention relates to rhizoma coptidis-containing azelaic acid gel as well as a preparation method and application thereof, and belongs to the technical field of azelaic acid gels, and the azelaic acid gel comprises the following raw material components in percentage by total mass of 100%: 0.01-1% of rhizoma coptidis extract, 5-20% of azelaic acid, 0.3-3% of ammonium acryloyldimethyl taurate / VP copolymer and 77-92% of 1, 3-propylene glycol. The rhizoma coptidis-containing azelaic acid gel prepared by the invention realizes multi-channel intervention such as antibiosis, anti-inflammation and cutin regulation on acnes, and separation of azelaic acid in the gel at low temperature can be effectively inhibited.

Description

Technical Field

[0001] This application relates to the field of azelaic acid gel technology, and in particular to an azelaic acid gel containing Coptis chinensis, its preparation method and uses. Background Technology

[0002] While the azelaic acid gel preparation prepared by the prior art "202210830395.2" has good efficacy in treating acne, and the addition of 1,3-propanediol as a solvent can prevent the precipitation of azelaic acid at low temperatures, users may experience side effects such as itching, burning, stinging, and redness during actual use. Therefore, to alleviate these side effects, the prior art often adds anti-inflammatory agents, such as bisabolol, tea tree oil, or plant extracts. When using oily components such as bisabolol and tea tree oil, it is often necessary to add an appropriate amount of antioxidant, which increases manufacturing costs and complicates the preparation process. Moreover, the addition of bisabolol and tea tree oil changes the appearance of the system from transparent to semi-transparent, thus affecting the product's appearance. Additionally, the addition of tea tree oil, due to its high permeability, can increase irritation. Common plant extracts, such as purslane extract and aloe vera extract mentioned in the prior art, usually contain multiple complex components, which can affect the stability of the gel preparation (-20). (It precipitates easily at -10 ℃, and the precipitated crystals are relatively large). Furthermore, in existing technologies, to further improve the exfoliating and acne-reducing effects of azelaic acid gel formulations and simultaneously extend their shelf life, existing technologies pre-complicate the exfoliant salicylic acid and the preservative o-cymene-5-ol. These auxiliary additives may themselves be irritants or sensitizers for some people with sensitive skin, further increasing the burden on the skin and the risk of adverse reactions. Moreover, the prepared gel precipitates a small amount of crystals after being placed at -10 ℃ for 24 hours, and as time goes on, crystals continue to precipitate, with the average particle size of the precipitated crystals gradually increasing, significantly increasing the gritty feeling during application and exacerbating skin irritation. Summary of the Invention

[0003] The purpose of this application is to address the shortcomings of existing azelaic acid gel formulations, which, when combined with conventional anti-inflammatory agents, cannot simultaneously relieve side effects such as itching and redness while effectively reducing the precipitation of azelaic acid crystals when placed at low temperatures. Therefore, this application proposes an azelaic acid gel containing Coptis chinensis, its preparation method, and its uses. This application combines a certain amount of azelaic acid, ammonium acryloyldimethyl taurate / VP copolymer, 1,3-propanediol, and Coptis chinensis extract. Azelaic acid mainly inhibits Propionibacterium acnes and regulates keratinization. Coptis chinensis extract is used to inhibit the release of skin inflammatory factors and relieve side effects such as itching, burning, stinging, and redness. Using 1,3-propanediol as a penetration enhancer can improve the transdermal absorption rate of azelaic acid. Using ammonium acryloyldimethyl taurate / VP copolymer as a stabilizing component can improve the solubility of azelaic acid and the stability of the product. At the same time, azelaic acid and Coptis chinensis extract can produce a synergistic effect, achieving multi-pathway intervention for acne, including antibacterial, anti-inflammatory, and keratinization regulation. Furthermore, the combination of azelaic acid and Coptis chinensis extract can reduce the degree of azelaic acid crystal precipitation after the prepared azelaic acid gel is placed at low temperature for a period of time.

[0004] In a first aspect, the azelaic acid gel containing Coptis chinensis provided in this application adopts the following technical solution: based on the total mass of the raw material components of the azelaic acid gel as 100%, the raw material components include: 0.01~1% Coptis chinensis extract, specifically, for example, 0.01%, 0.1%, 0.3%, 0.5%, 0.8% or 1%; 5~20% azelaic acid, specifically, for example, 5%, 8%, 10%, 15%, 18% or 20%; 0.3~3% ammonium acryloyldimethyl taurate / VP copolymer, specifically, for example, 0.3%, 0.5%, 1%, 1.5%, 2%, 2.5%, 2.7% or 3%; 77~92% 1,3-propanediol, specifically, for example, 77%, 79%, 85%, 89% or 92%.

[0005] Through the above technical solution, this application utilizes azelaic acid, ammonium acryloyldimethyl taurate / VP copolymer, 1,3-propanediol, and Coptis chinensis extract in combination to achieve multi-pathway intervention in acne, including antibacterial, anti-inflammatory, and keratin-regulating effects. Because Coptis chinensis extract is rich in various bioactive components (such as berberine), it exhibits significant anti-inflammatory activity and can inhibit pro-inflammatory cytokines (such as TNF-α). The production of IL-1β can directly counteract and alleviate skin inflammatory reactions (such as redness and stinging) induced by azelaic acid. Simultaneously, the rigid planar structure of berberine in Coptis chinensis extract is crucial; it can form intermolecular forces with the carboxyl groups of azelaic acid through π-π stacking. At low temperatures, this stacking interferes with the regular arrangement of azelaic acid molecules, thereby inhibiting crystal growth. The quaternary ammonium cations and phenolic hydroxyl groups in berberine molecules can form hydrogen bond networks with propylene glycol solvent. This network structure may increase the viscosity of the system, reduce the migration rate of azelaic acid molecules, and decrease the tendency to crystallize. Based on the total mass of the raw material components of the azelaic acid gel being 100%, when the... When the content of Coptis chinensis extract is less than 0.01%, the anti-allergic effect of the system will not meet the requirements. When the content of Coptis chinensis extract is greater than 1%, the consistency of the system decreases too quickly and cannot form a gel. When the content of azelaic acid is less than 5%, the acne-removing effect is greatly reduced. When the content of azelaic acid is greater than 20%, the stability of the system is problematic, resulting in precipitation at low temperatures. When the content of ammonium acryloyldimethyl taurate / VP copolymer is less than 0.3%, the consistency of the system cannot form a gel. When the content of ammonium acryloyldimethyl taurate / VP copolymer is greater than 3%, the consistency of the system is too high, making it extremely inconvenient to use.

[0006] Optionally, the raw material components include: 0.1-0.5% Coptis chinensis extract, 18-20% azelaic acid, 2.5-3% ammonium acryloyldimethyl taurate / VP copolymer and 77-79% 1,3-propanediol.

[0007] By optimizing the contents of Coptis chinensis extract, azelaic acid, ammonium acryloyldimethyl taurate / VP copolymer, and 1,3-propanediol, the anti-inflammatory and antioxidant effects of azelaic acid gel containing Coptis chinensis can be improved simultaneously, while reducing the precipitation of azelaic acid under low temperature conditions.

[0008] Further optionally, the mass ratio of azelaic acid to Coptis chinensis extract is 40-60:1, specifically, for example, 40, 47.5, 50 or 60.

[0009] Through the above technical solution, when the mass ratio of azelaic acid to Coptis chinensis extract is less than 40:1, excessive berberine competes with the copolymer for hydrogen bond sites, destroys the gel network structure, and increases the crystallization risk of the gel formulation. When the mass ratio of azelaic acid to Coptis chinensis extract is greater than 60:1, the berberine concentration is insufficient, the antibacterial and anti-inflammatory effects are reduced, and the insufficient berberine leads to a decrease in π-π stacking density, increasing the crystallization risk of the gel formulation.

[0010] Alternatively, the raw material components may include: 0.3% Coptis chinensis extract, 18% azelaic acid, 2.7% ammonium acryloyldimethyl taurate / VP copolymer and 79% 1,3-propanediol.

[0011] By further optimizing the content of Coptis chinensis extract, azelaic acid, ammonium acryloyl dimethyl taurate / VP copolymer and 1,3-propanediol through the above technical solution, the prepared Coptis chinensis azelaic acid gel can have antibacterial, anti-inflammatory, oil-controlling and keratinization-regulating effects, and can relieve side effects such as itching, burning, stinging and redness, while no crystal precipitation occurs when placed at -20℃ for 60 days.

[0012] Secondly, this application provides a method for preparing the azelaic acid gel containing Coptis chinensis as described above, the preparation method comprising the following steps: S1. Take a portion of the 1,3-propanediol and heat it to 70~80 °C, specifically, for example, 70 °C, 72 °C, 74 °C, 76 °C, 78 °C or 80 °C. Add the azelaic acid to the heated 1,3-propanediol and stir evenly to form a first mixed system. Then add the remaining portion of the 1,3-propanediol to the first mixed system and mix evenly to form a second mixed system. S2. Cool the second mixture to 40~60 ℃, specifically, for example, 40 ℃, 45 ℃, 50 ℃, 55 ℃ or 60 ℃, and add the Coptis chinensis extract to the cooled second mixture for homogenization to obtain a homogenized system. S3. Add a portion of the ammonium acryloyldimethyl taurate / VP copolymer to the homogeneous system and stir until homogeneous to form a primary gel. Then, cool the primary gel to <40 ℃, specifically, for example, 25 ℃, 30 ℃ or 35 ℃, and add the remaining portion of the ammonium acryloyldimethyl taurate / VP copolymer to the cooled primary gel. Let it stand to obtain azelaic acid gel containing Coptis chinensis.

[0013] Through the above technical solution, the solubility of azelaic acid in 1,3-propanediol is limited at room temperature. The heating process in step S1 provides energy, which is used to break the strong lattice energy of azelaic acid and greatly enhances the thermal motion of solute and solvent molecules. This allows more azelaic acid molecules to break free from solid bonds and diffuse into the solvent. At the same time, heating also significantly reduces the viscosity of 1,3-propanediol (a viscous liquid), which further promotes mass transfer and dissolution rates, thus forming a saturated or near-saturated solution at high temperature. In step S1, when a portion of the 1,3-propanediol is heated below 70°C, the azelaic acid is not completely dissolved, leading to local concentration gradients that cause aggregation, reducing the concentration of azelaic acid in the gel and worsening the antibacterial effect. When a portion of the 1,3-propanediol is heated above 80°C... At ℃, azelaic acid becomes locally supersaturated. After the prepared gel formulation is placed at a low temperature for a period of time, the precipitation of azelaic acid increases. At the same time, the purpose of adding 1,3-propanediol in batches in step S1 is to avoid the azelaic acid powder from agglomerating due to excessive solvent contact at one time, and to prevent the formation of microcrystal nuclei due to rapid dissolution and precipitation of azelaic acid. In step S2, the Coptis chinensis extract is added to the second mixed system cooled to 40~60 ℃ to ensure the chemical structure of berberine in the Coptis chinensis extract is stable, so that berberine and the carboxyl group of azelaic acid form an appropriate amount of π-π stacking, thereby preventing the precipitation of azelaic acid. In step S3, the purpose of cooling the primary gel to <40 ℃ is to avoid high-temperature degradation, and at the same time, to optimize molecular interactions through the pre-action principle, strengthen the gel network to maintain antibacterial / anti-inflammatory efficacy and low irritation.

[0014] Optionally, step S1 further includes: after forming the second mixture system, keeping the second mixture system at a constant temperature of 70~80 ℃ for 6~24 h.

[0015] Through the above technical solution, azelaic acid, a dicarboxylic acid containing two carboxyl groups, and 1,3-propanediol containing two hydroxyl groups, can form hydrogen bonds between them after a period of time at a suitable temperature. This interaction allows the azelaic acid molecules to be better "wrapped" and "solventized" by the solvent molecules, thus existing more stably in the solution. Under isothermal conditions, tiny crystal nuclei in the solution (if present) may dissolve, while the solute molecules have sufficient time to diffuse and rearrange, ultimately reaching a uniform and stable state in the entire system. This eliminates local supersaturation differences. This process can be understood as "matured" the solution, transforming it from an unstable, easily precipitated metastable state to a more stable state, thereby significantly reducing the precipitation rate of azelaic acid in a berberine-containing azelaic acid gel after being placed at low temperature for a period of time.

[0016] Optionally, in step S1, 30-40% of the 1,3-propanediol is heated to 70-80°C, and the azelaic acid is added to the heated 1,3-propanediol and stirred evenly to form a first mixed system. Then, 60-70% of the 1,3-propanediol is added to the first mixed system and mixed evenly.

[0017] With the above technical solution, when a small amount of 1,3-propanediol (30~40%) is added initially to dissolve azelaic acid at 70~80℃, the heating rate is fast and the azelaic acid is more evenly dispersed. Then, the remaining 1,3-propanediol is added, and the local supersaturation is reduced through gradient dilution to prevent the formation of microcrystal nuclei due to rapid dissolution and precipitation of azelaic acid.

[0018] Optionally, in step S1, the azelaic acid is added to the heated 1,3-propanediol at a constant rate of 4-6 g / min; in step S1, the remaining portion of the 1,3-propanediol is added to the first mixing system at a constant flow rate of 8-12 mL / min.

[0019] By using the above technical solutions, the addition rate of azelaic acid is limited to 4~6 g / min to avoid local oversaturation, ensure uniform dissolution, reduce crystal nucleus formation, and control the flow rate of 1,3-propanediol to 8~12 mL / min to prevent sudden viscosity changes, maintain the gel network structure, and inhibit the precipitation of low-temperature crystals.

[0020] Optionally, 30-50% of the ammonium acryloyldimethyl taurate / VP copolymer is added to the homogeneous system and stirred evenly to form a primary gel. Then, the primary gel is cooled to 25-35°C, and 50-70% of the ammonium acryloyldimethyl taurate / VP copolymer is added to the cooled primary gel.

[0021] The above technical solution involves first adding 30-50% copolymer gelling agent to a homogeneous system. The copolymer partially swells to form a primary loose network, ensuring uniform dispersion of berberine and inhibiting excessive molecular chain extension in a low-temperature environment. Then, some copolymers are cross-linked in the gaps of the primary network to form a dense network structure. The dense network physically blocks the migration of azelaic acid and reduces the crystallization rate of azelaic acid at low temperatures.

[0022] Thirdly, this application provides the use of the aforementioned azelaic acid gel containing Coptis chinensis in the preparation of skin care products for treating acne.

[0023] In summary, this application includes at least one of the following beneficial technical effects: 1. The azelaic acid in the gel formulation described in this application has the effect of inhibiting Propionibacterium acnes and regulating keratinization. One of its core innovations lies in introducing Coptis chinensis extract into the azelaic acid gel system. Coptis chinensis extract is rich in various bioactive components, such as berberine, which has significant anti-inflammatory activity and can inhibit pro-inflammatory cytokines (such as TNF-α). The production of IL-1β can directly counteract and alleviate skin inflammatory reactions (such as redness and stinging) caused by azelaic acid, thereby achieving multi-pathway intervention for acne, including antibacterial, anti-inflammatory, and keratin regulation. At the same time, because berberine in Coptis chinensis extract has a rigid planar structure, it can form intermolecular forces with the carboxyl groups of azelaic acid through π-π stacking. This π-π stacking can inhibit the growth of azelaic acid crystal nuclei. Furthermore, the quaternary ammonium cations and phenolic hydroxyl groups in berberine molecules can form hydrogen bond networks with 1,3-propanediol solvent. This hydrogen bond network can reduce the tendency to crystallize, thereby reducing the degree of azelaic acid crystal precipitation after the prepared azelaic acid gel is placed at low temperature for a period of time. This makes it suitable for the use of azelaic acid gel formulation containing Coptis chinensis extract in extremely cold regions. 2. The gel formulation described in this application uses a specific penetration enhancer, 1,3-propanediol, which can significantly improve the transdermal absorption rate of the active ingredients in azelaic acid and Coptis chinensis extract, making it easier for the active ingredients to reach the target site and enhance the therapeutic effect. At the same time, it uses ammonium acryloyl dimethyl taurate / VP copolymer as a stabilizing ingredient to improve the solubility of azelaic acid and the stability of the product, resulting in a more refreshing skin feel and avoiding the heavy feeling of traditional oily creams. 3. The preparation method described in this application actively stabilizes easily precipitated azelaic acid in advance through precise temperature zoning and staged material mixing sequence, and protects the heat and shear force sensitive gelling agent (ammonium acryloyl dimethyl taurate / VP copolymer) and natural additive (Coptis chinensis extract) throughout the process, so that azelaic acid and Coptis chinensis extract can be effectively combined. This allows the prepared gel formulation to have the advantages of antibacterial, anti-inflammatory and low irritation, while effectively reducing the degree of azelaic acid precipitation when the gel formulation is placed at low temperature. 4. The gel formulation described in this application helps to improve facial redness and papules when treating acne. At the same time, since both azelaic acid and Coptis chinensis extract have an inhibitory effect on abnormally active melanocytes, they help to fade pigmentation left by acne scars. In addition, the gel formulation described in this application is free of fragrances and preservatives. This design significantly reduces the risk of skin irritation or allergies caused by these additional ingredients, making the formula more concise and gentle, and providing a safer option, especially for people with sensitive skin or consumers who pursue minimalist skincare. Attached Figure Description

[0024] Figure 1 The images show the azelaic acid gel containing Coptis chinensis prepared in Examples 1-3 after being placed at -20 °C for 60 days. Figure 2A physical image of the azelaic acid gel prepared for Comparative Example 1 after being placed at -20 °C for 60 days; Figure 3 A physical image of the azelaic acid gel prepared for Comparative Example 11 after being placed at -20 °C for 60 days. Detailed Implementation

[0025] The following combination Figures 1-3 The present application will be further described in detail with reference to specific embodiments.

[0026] The following examples further illustrate the azelaic acid gel containing Coptis chinensis, its preparation method, and its uses as described in this application. The examples are implemented based on the technical solution of this application, providing detailed implementation methods and specific operating procedures; however, the scope of protection of this application is not limited to the following examples.

[0027] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods in the art. Unless otherwise specified, the experimental materials used in the following embodiments are commercially available.

[0028] Coptis chinensis extract: purchased from Bozhou Xier Traditional Chinese Medicine Co., Ltd.; Purslane extract: purchased from Shaanxi Jinrun Biotechnology Co., Ltd.; Aloe vera extract: purchased from Shaanxi Jinrun Biotechnology Co., Ltd. Acryloyldimethyltaurate ammonium / VP copolymer: purchased from Clariant Produkte (Deutschland) GmbH.

[0029] Example 1

[0030] A coptis-containing azelaic acid gel, with a total raw material quantity of 100 g, based on the total mass of the raw material components of the azelaic acid gel as 100%, the raw material components include: 0.1% coptis extract, 5% azelaic acid, 2.9% ammonium acryloyldimethyl taurate / VP copolymer and 92% 1,3-propanediol.

[0031] A method for preparing azelaic acid gel containing Coptis chinensis, the method comprising the following steps: S1. Take 30% of the 1,3-propanediol and heat it to 70 °C. Then, add the azelaic acid to the heated 1,3-propanediol at a constant rate of 5 g / min and stir until homogeneous (stirring rate is 500 rpm, stirring time is 10 min) to form a first mixed system. Then, add the remaining 1,3-propanediol to the first mixed system at a constant flow rate of 10 mL / min and mix until homogeneous to form a second mixed system. S2. Cool the second mixture to 60 °C, and add the Coptis chinensis extract to the cooled second mixture for homogenization. The homogenization conditions are: 3000 rpm for 10 min to obtain a homogenized system. S3. Add 30% of the ammonium acryloyldimethyl taurate / VP copolymer to the homogeneous system and stir evenly (stirring speed is 800 rpm, stirring time is 15 min) to form a primary gel. Then, cool the primary gel to 35°C and add the remaining ammonium acryloyldimethyl taurate / VP copolymer to the cooled primary gel. Let it stand for 2 h to obtain azelaic acid gel containing Coptis chinensis.

[0032] Example 2

[0033] The preparation method of Example 1 was carried out, except that a coptis-containing azelaic acid gel was prepared, with a total raw material amount of 100 g. The raw material components of the azelaic acid gel were 100% based on the total mass of the raw material components, which included: 0.5% coptis extract, 10% azelaic acid, 0.5% ammonium acryloyldimethyl taurate / VP copolymer and 89% 1,3-propanediol.

[0034] Example 3

[0035] The preparation method of Example 1 was implemented, except that a coptis-containing azelaic acid gel was prepared, with a total raw material amount of 100 g. The raw material components of the azelaic acid gel were 100% based on the total mass of the raw material components, which included: 1% coptis extract, 20% azelaic acid, 2% ammonium acryloyldimethyl taurate / VP copolymer and 77% 1,3-propanediol.

[0036] Example 4

[0037] The preparation method of Example 1 was implemented, except that a coptis-containing azelaic acid gel was prepared, with a total raw material amount of 100 g. The raw material components of the azelaic acid gel were 100% based on the total mass of the raw material components, which included: 0.5% coptis extract, 20% azelaic acid, 2.5% ammonium acryloyldimethyl taurate / VP copolymer and 77% 1,3-propanediol.

[0038] Example 5

[0039] The preparation method of Example 1 was carried out, except that a coptis-containing azelaic acid gel was prepared, with a total raw material amount of 100 g. The raw material components of the azelaic acid gel were 100% based on the total mass of the raw material components, which included: 0.3% coptis extract, 18% azelaic acid, 2.7% ammonium acryloyldimethyl taurate / VP copolymer and 79% 1,3-propanediol.

[0040] Example 6

[0041] The preparation method and raw material composition of Example 1 were followed, except that step S1 in the preparation method was different. Specifically, 30% of the 1,3-propanediol was heated to 80 °C.

[0042] Example 7

[0043] The preparation method and raw material composition of Example 1 were implemented, except that step S2 in the preparation method was different. Specifically, the second mixture was cooled to 40 °C, and the Coptis chinensis extract was added to the cooled second mixture for homogenization.

[0044] Example 8

[0045] The preparation method and raw material composition of Example 1 were implemented, except that step S3 in the preparation method was different. Specifically, the primary gel was then cooled to 25°C, and the remaining ammonium acryloyl dimethyl taurate / VP copolymer was added to the cooled primary gel.

[0046] Example 9

[0047] The process is carried out according to the raw material composition of Example 5, except that step S1 further includes: after forming the second mixture system, the second mixture system is kept at a constant temperature of 70 °C for 24 h, specifically: A method for preparing azelaic acid gel containing Coptis chinensis, the method comprising the following steps: S1. Take 30% of the 1,3-propanediol and heat it to 70 °C. Then, add the azelaic acid to the heated 1,3-propanediol at a constant rate of 5 g / min and stir until homogeneous (stirring rate is 500 rpm, stirring time is 10 min) to form a first mixing system. Then, add the remaining 1,3-propanediol to the first mixing system at a constant flow rate of 10 mL / min and mix until homogeneous to form a second mixing system. Let the second mixing system stand at 70 °C for 24 h. S2. Cool the second mixture to 60 °C, and add the Coptis chinensis extract to the cooled second mixture for homogenization. The homogenization conditions are: 3000 rpm for 10 min to obtain a homogenized system. S3. Add 30% of the ammonium acryloyldimethyl taurate / VP copolymer to the homogeneous system and stir evenly (stirring speed is 800 rpm, stirring time is 15 min) to form a primary gel. Then, cool the primary gel to 35°C and add the remaining ammonium acryloyldimethyl taurate / VP copolymer to the cooled primary gel. Let it stand for 2 h to obtain azelaic acid gel containing Coptis chinensis.

[0048] Example 10

[0049] The method is implemented in accordance with Example 9, except that in step S1, the second mixture is kept at a constant temperature of 80 °C for 10 h.

[0050] Example 11

[0051] The preparation method and raw material composition of Example 1 were followed, except that step S1 in the preparation method was different. Specifically, 70% of the 1,3-propanediol was heated to 70 °C.

[0052] Example 12

[0053] The preparation method and raw material composition of Example 1 were implemented, except that the addition rates of azelaic acid and 1,3-propanediol in step S1 of the preparation method were different. Specifically, 30% of the 1,3-propanediol was heated to 70 °C, and azelaic acid was added to the heated 1,3-propanediol at a constant rate of 2 g / min and stirred evenly (stirring rate of 500 rpm, stirring time of 10 min) to form a first mixed system. Then, the remaining 1,3-propanediol was added to the first mixed system at a constant flow rate of 5 mL / min and mixed evenly to form a second mixed system.

[0054] Example 13

[0055] The preparation method and raw material composition of Example 1 were implemented, except that the addition rates of azelaic acid and 1,3-propanediol in step S1 of the preparation method were different. Specifically, 30% of the 1,3-propanediol was heated to 70 °C, and the azelaic acid was added to the heated 1,3-propanediol at a constant rate of 8 g / min and stirred evenly (stirring rate of 500 rpm, stirring time of 10 min) to form a first mixed system. Then, the remaining 1,3-propanediol was added to the first mixed system at a constant flow rate of 15 mL / min and mixed evenly to form a second mixed system.

[0056] Comparative Example 1 The preparation method of Example 1 was implemented, except that an azelaic acid gel was prepared, with a total raw material amount of 100 g. The raw material components of the azelaic acid gel were 100% based on the total mass of the raw material components, which included: 0.5% purslane extract, 10% azelaic acid, 0.5% ammonium acryloyldimethyl taurate / VP copolymer and 89% 1,3-propanediol.

[0057] Comparative Example 2 The preparation method of Example 1 was implemented, except that an azelaic acid gel was prepared, with a total raw material amount of 100 g. The raw material components of the azelaic acid gel were 100% based on the total mass of the raw material components, which included: 0.5% aloe vera extract, 10% azelaic acid, 0.5% ammonium acryloyldimethyl taurate / VP copolymer and 89% 1,3-propanediol.

[0058] Comparative Example 3 The preparation method of Example 1 was implemented, except that the Coptis chinensis extract was replaced with an equal amount of azelaic acid. Specifically, an azelaic acid gel was prepared, with a total raw material weight of 100 g. The raw material components of the azelaic acid gel were 100% based on the total mass of the raw material components, which included: 5.1% azelaic acid, 2.9% ammonium acryloyldimethyl taurate / VP copolymer, and 92% 1,3-propanediol.

[0059] Comparative Example 4 The preparation method of Example 1 was carried out, except that a coptis-containing azelaic acid gel was prepared, with a total raw material amount of 100 g. The raw material components of the azelaic acid gel were 100% based on the total mass of the raw material components, which included: 1.5% coptis extract, 22% azelaic acid, 2.5% ammonium acryloyldimethyl taurate / VP copolymer and 74% 1,3-propanediol.

[0060] Comparative Example 5 The preparation method and raw material composition of Example 1 were followed, except that step S1 in the preparation method was different. Specifically, 30% of the 1,3-propanediol was heated to 60 °C.

[0061] Comparative Example 6 The preparation method and raw material composition of Example 1 were followed, except that step S1 in the preparation method was different. Specifically, 30% of the 1,3-propanediol was heated to 90 °C.

[0062] Comparative Example 7 The preparation method and raw material composition of Example 1 were followed, except that step S1 in the preparation method was different, specifically: S1. Heat the 1,3-propanediol to 70 °C, and add the azelaic acid to the heated 1,3-propanediol at a constant rate of 5 g / min and stir until homogeneous (stirring rate is 500 rpm, stirring time is 10 min) to form a mixed system. S2. Cool the mixture to 60 °C, and add the Coptis chinensis extract to the cooled mixture for homogenization. The homogenization conditions are: 3000 rpm for 10 min to obtain a homogenized system. S3. Add 30% of the ammonium acryloyldimethyl taurate / VP copolymer to the homogeneous system and stir evenly (stirring speed is 800 rpm, stirring time is 15 min) to form a primary gel. Then, cool the primary gel to 35°C and add the remaining ammonium acryloyldimethyl taurate / VP copolymer to the cooled primary gel. Let it stand for 2 h to obtain azelaic acid gel containing Coptis chinensis.

[0063] Comparative Example 8 The preparation method and raw material composition of Example 1 were implemented, except that step S2 in the preparation method was different. Specifically, the second mixture was cooled to 30 °C, and the Coptis chinensis extract was added to the cooled second mixture for homogenization.

[0064] Comparative Example 9 The preparation method and raw material composition of Example 1 were implemented, except that step S2 in the preparation method was different. Specifically, the second mixture was cooled to 70 °C, and the Coptis chinensis extract was added to the cooled second mixture for homogenization.

[0065] Comparative Example 10 The preparation method and raw material composition of Example 1 were followed, except that step S3 in the preparation method was different. Specifically, 30% of the ammonium acryloyl dimethyl taurate / VP copolymer was added to the homogeneous system and stirred evenly (stirring speed of 800 rpm and stirring time of 15 min) to form a primary gel. Then, the primary gel was cooled to 40°C, and the remaining ammonium acryloyl dimethyl taurate / VP copolymer was added to the cooled primary gel. After standing for 2 hours, azelaic acid gel containing Coptis chinensis was obtained.

[0066] Comparative Example 11 The preparation method and raw material composition of Example 1 were followed, except that step S3 in the preparation method was different. Specifically, the homogenized system was cooled to 35°C, and the ammonium acryloyl dimethyl taurate / VP copolymer was added to the homogenized system and stirred evenly (stirring rate of 800 rpm, stirring time of 15 min). After standing for 2 h, azelaic acid gel containing Coptis chinensis was obtained.

[0067] Test case Assay for inhibiting the growth of Propionibacterium acnes: Propionibacterium acnes was cultured to the logarithmic growth phase, and the OD of the bacterial culture was measured using an enzyme-linked immunosorbent assay (ELISA) reader. 600 Adjust the bacterial concentration by adding 100 μL of *Propionibacterium acnes* suspension (2.5 × 10⁵ CFU / mL) to each well of a 96-well plate. Azelaic acid gels prepared in Examples 1-13 and Comparative Examples 1-11 were used as experimental groups. A positive control group (BHI medium + 2.5 × 10⁵ CFU / mL *Propionibacterium acnes*) and a negative control group (medium medium) were also set up. The inoculated 96-well plates were placed in anaerobic culture bags and incubated at 37 °C for 48 h. Based on OD... 600 The antibacterial rate was calculated from the OD value measured at nm: Antibacterial rate (%) = (OD value of positive control group - OD value of experimental group) / (OD value of positive control group - OD value of negative control group) × 100%; Assay to inhibit the expression level of the inflammatory cytokine interleukin-1β (IL-1β): Human keratinocytes (HaCaT cells) in logarithmic growth phase were collected, and the cell concentration was adjusted to be seeded at a density of 2 × 10⁵ cells / well in 96-well cell culture plates and cultured for 24 h. After culture, azelaic acid gels prepared in Examples 1-13 and Comparative Examples 1-11 were added to each well to ensure that the final concentrations at each dose were the same. After pretreatment for 1 h, 4 × 10⁷ CFU / well of inactivated Propionibacterium acnes (C. acnes) was added to each well. After culturing for another 23 h, cells were collected and RNA was extracted for qPCR detection. The relative mRNA expression level of IL-1β was calculated using the 2-ΔΔCt method. Low-temperature storage test: Azelaic acid gel was subjected to cold resistance at -20 ℃ for 60 days, and the precipitation of azelaic acid crystals was observed.

[0068] The azelaic acid coagulants containing Coptis chinensis from Examples 1-13 and the azelaic acid coagulants prepared from Comparative Examples 1-11 were subjected to tests for inhibiting the growth of Propionibacterium acnes, inhibiting IL-1β expression levels, and low-temperature storage. The test results are shown in Table 1. Table 1

[0069] As can be seen from Table 1, the raw material components and preparation method of the azelaic acid gel described in this application can achieve multi-pathway intervention for acne, including antibacterial, anti-inflammatory, and keratin regulation. At the same time, it can reduce the degree of azelaic acid crystal precipitation after the prepared azelaic acid gel is placed at low temperature for a period of time. Even if a small amount of precipitation occurs, the particle size of the precipitated crystals is small and will not increase the irritation to the skin when applied.

[0070] The embodiments described in this specific implementation are preferred embodiments of this application and are not intended to limit the scope of protection of this application.

Claims

1. A azelaic acid gel containing coptis, characterized in that, The raw material components include 0.01-1% of the extract of Coptis deltoidea, 5-20% of azelaic acid, 0.3-3% of acryloyldimethyltaurine ammonium / VP copolymer and 77-92% of 1,3-propanediol, based on the total mass of the raw material components of the azelaic acid gel being 100%.

2. The azelaic acid gel containing coptis of claim 1, wherein, The raw material components include 0.1-0.5% of the extract of Coptis deltoidea, 18-20% of azelaic acid, 2.5-3% of acryloyldimethyltaurine ammonium / VP copolymer and 77-79% of 1,3-propanediol.

3. The azelaic acid gel containing coptis of claim 1 or 2, characterized in that, The mass ratio of the azelaic acid to the extract of Coptis deltoidea is 40-60:

1.

4. The azelaic acid gel containing coptis of claim 1, wherein, The raw material components include 0.3% of the extract of Coptis deltoidea, 18% of azelaic acid, 2.7% of acryloyldimethyltaurine ammonium / VP copolymer and 79% of 1,3-propanediol.

5. A process for the preparation of the azelaic acid gel containing coptis of any one of claims 1 to 4, characterized in that, The preparation method includes the following steps: S1, a part of the 1,3-propanediol is heated to 70-80 ℃, the azelaic acid is added to the heated 1,3-propanediol and stirred uniformly to form a first mixed system, and then the remaining part of the 1,3-propanediol is added to the first mixed system and mixed uniformly to form a second mixed system; S2, the second mixed system is cooled to 40-60 ℃, and the extract of Coptis deltoidea is added to the cooled second mixed system for homogenization treatment to obtain a homogenization system; S3, a part of the acryloyldimethyltaurine ammonium / VP copolymer is added to the homogenization system and stirred uniformly to form a primary gel, the primary gel is then cooled to <40 ℃, the remaining part of the acryloyldimethyltaurine ammonium / VP copolymer is added to the cooled primary gel, and the azelaic acid gel containing Coptis deltoidea is obtained after standing.

6. The method of claim 5, wherein the preparation of the azelaic acid gel containing coptis is characterized by, Step S1 further includes: after the second mixed system is formed, the second mixed system is kept at a constant temperature of 70-80 ℃ for 6-24 h.

7. The method of claim 5 or 6, wherein the preparation of the azelaic acid gel containing coptis rhizome is characterized by, In step S1, 30-40% of the 1,3-propanediol is heated to 70-80 ℃, the azelaic acid is added to the heated 1,3-propanediol and stirred uniformly to form a first mixed system, and then 60-70% of the 1,3-propanediol is added to the first mixed system and mixed uniformly.

8. The method of claim 5 or 6, wherein the preparation of the azelaic acid gel containing coptis rhizome is characterized by, In step S1, the azelaic acid is added to the heated 1,3-propanediol at a constant rate, wherein the constant rate is 4-6 g / min; In step S1, the remaining part of the 1,3-propanediol is added to the first mixed system at a constant flow rate, wherein the constant flow rate is 8-12 mL / min.

9. The method of claim 5 or 6, wherein the preparation of the azelaic acid gel containing coptis rhizome is characterized by, 30-50% of the acryloyldimethyltaurine ammonium / VP copolymer is added to the homogenization system and stirred uniformly to form a primary gel, and then the primary gel is cooled to 25-35 ℃, and 50-70% of the acryloyldimethyltaurine ammonium / VP copolymer is added to the cooled primary gel.

10. Use of the azelaic acid gel containing Coptis deltoidea according to any one of claims 1-4 in the preparation of a skin care product for treating acne.

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