Skin bacteriostatic repair emulsion and preparation method thereof
By reacting cinnamaldehyde with octadecylamine to form a cinnamaldehyde-octadecylamine complex, and covalently coupling paeonol with octadecylamine to form a paeonol-octadecylamine covalent couple, and dispersing these compounds in an aqueous phase, the problem of poor stability of cinnamaldehyde and paeonol was solved, thereby improving the stability and therapeutic effect of the skin antibacterial repair emulsion.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- LINYI UNIVERSITY
- Filing Date
- 2023-04-28
- Publication Date
- 2026-06-23
AI Technical Summary
Cinnamaldehyde, paeonol, and asiatic acid have drawbacks in the preparation of drugs for treating acne, including poor water solubility, easy oxidation, and unstable properties, which limits their widespread application.
Cinnamaldehyde was reacted with octadecylamine to form a cinnamaldehyde-octadecylamine complex. Paeonol was covalently coupled with octadecylamine to form a paeonol-octadecylamine covalent couple. This was then dispersed together with asiatic acid in an aqueous phase to form droplets with a particle size of less than 200 nm. An emulsifier was used to improve stability and solubility.
The stability of cinnamaldehyde and paeonol has been improved, enhancing the therapeutic effect on acne and reducing the greasy feeling, thus achieving both stability and therapeutic effect in the skin antibacterial repair lotion.
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Figure CN116270462B_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of cosmetics, and more specifically, to a skin antibacterial repair lotion and its preparation method. Background Technology
[0002] Acne, also known as pimples or blackheads, is a skin condition caused by blocked hair follicles and sebaceous glands. This blockage allows oil, bacteria, and fungi to accumulate, triggering an inflammatory reaction. The inflammation causes redness and swelling, further worsening the skin's condition. Acne can also cause skin damage, easily leaving scars during the skin's natural repair process. These scars not only affect appearance but can also impact mental health. Therefore, inhibiting bacterial and fungal infections, alleviating inflammation, promoting skin repair, and reducing scar formation are effective treatments for acne.
[0003] Currently, there are several substances available for treating acne, such as cinnamaldehyde, paeonol, and asiatic acid. Cinnamaldehyde is the main active ingredient in the traditional Chinese medicine cinnamon. It has low irritation and not only has a good inhibitory effect on various bacteria but also inhibits fungi by disrupting their cell walls. Paeonol has anti-inflammatory, swelling-reducing, analgesic, anti-allergic, and antiviral effects, and can also inhibit intracellular O2. 2- Free radicals are generated, reducing and fading pigment deposits in the skin, thus lessening skin pigmentation. Centella asiatica acid has anti-inflammatory effects, inhibits scar fibroblast proliferation, and promotes wound healing, with a particularly significant effect on inhibiting scar fibroblast proliferation.
[0004] However, cinnamaldehyde, paeonol, and asiatic acid have some defects in their physicochemical properties, which limit their widespread application. For example, cinnamaldehyde is an oily liquid that is poorly soluble in water, easily oxidized, volatile, and unstable; paeonol has poor water solubility, and the phenolic hydroxyl groups in its structure are easily oxidized; although asiatic acid is more stable than cinnamaldehyde and paeonol, it has poor water solubility.
[0005] Therefore, improving the physicochemical properties of cinnamaldehyde, paeonol, and asiatic acid is an urgent problem to be solved when preparing drugs for treating acne. Summary of the Invention
[0006] This application provides a skin antibacterial repair emulsion and its preparation method, which can effectively improve the physicochemical properties of cinnamaldehyde, paeonol and asiatic acid, enabling them to exist stably and in large quantities in actual use, and has a good therapeutic effect on acne.
[0007] In a first aspect, embodiments of this application provide a skin antibacterial repair emulsion, the components of which include an oil phase, an aqueous phase, and an emulsifier, and the components of the oil phase are dispersed in the aqueous phase in the form of droplets under the action of the emulsifier, the droplet particle size being less than 200 nm; the components of the oil phase include at least one of cinnamaldehyde octadecylamine complex, paeonol octadecylamine covalently coupled compound, and asiatic acid.
[0008] In the above technical solution, the emulsifier enables the oil phase to be dispersed in the aqueous phase in the form of droplets, thereby increasing the solubility and stability of the components in the oil phase in water; in addition, the droplets of the oil phase dispersed in the aqueous phase have a particle size of less than 200 nm, so the oil phase can more easily penetrate the epidermis through skin appendages. The microemulsion reduces the greasy feeling of the oily drug and facilitates topical drug delivery.
[0009] Furthermore, the cinnamaldehyde-octadecylamine complex in the oil phase is a product of the reaction between cinnamaldehyde and octadecylamine. This complex masks the molecular structure of cinnamaldehyde, improving its stability. Moreover, during use, the cinnamaldehyde-octadecylamine complex reverts to cinnamaldehyde, retaining its therapeutic effect. The paeonol-octadecylamine covalently coupled compound is a product of the covalent interaction between the amino group in octadecylamine and the phenolic hydroxyl group in the paeonol structure. This prevents the oxidation of the phenolic hydroxyl group in the paeonol structure, improving its stability. Therefore, the cinnamaldehyde-octadecylamine complex and the paeonol-octadecylamine covalently coupled compound in the oil phase retain the therapeutic effects of cinnamaldehyde and paeonol while exhibiting better stability. When used in skin antibacterial and repairing lotions, they effectively improve skin health and enhance the treatment effect on acne.
[0010] Secondly, embodiments of this application provide a method for preparing a skin antibacterial repair emulsion according to the first aspect, which includes the following steps: mixing an oil phase, an aqueous phase and an emulsifier and stirring, so that the oil phase is dispersed in the aqueous phase in the form of droplets under the action of the emulsifier, and the droplet particle size does not exceed 200 nm; wherein the components of the oil phase include at least one of cinnamaldehyde octadecylamine complex, paeonol octadecylamine covalently coupled compound and asiatic acid.
[0011] The skin antibacterial repair lotion prepared using the above method has relatively stable components, high solubility in the oil phase, and good therapeutic effect on acne, which can significantly improve skin health. Attached Figure Description
[0012] To more clearly illustrate the technical solutions of the embodiments of this application, the accompanying drawings used in the embodiments of this application will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this application and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.
[0013] Figure 1 This image shows the changes in acne on a volunteer's face. Detailed Implementation
[0014] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions in the embodiments of this application will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.
[0015] The following is a detailed description of the skin antibacterial repair emulsion and its preparation method according to the embodiments of this application.
[0016] The skin antibacterial repair emulsion of this application embodiment comprises an oil phase, an aqueous phase, and an emulsifier. The components of the oil phase are dispersed in the aqueous phase in the form of droplets under the action of the emulsifier, and the droplet size does not exceed 200 nm. The components of the oil phase include at least one of cinnamaldehyde octadecylamine complex, paeonol octadecylamine covalently coupled compound, and asiatic acid.
[0017] When the oil phase exists in the aqueous phase as droplets, an emulsion is formed. This increases both the solubility and stability of the oil phase, thus enhancing the therapeutic effect of the skin antibacterial and repairing emulsion. Furthermore, the droplet size of the oil phase dispersed in the aqueous phase is generally below 200 nm (this is generally called a microemulsion). This allows the oil phase to penetrate the epidermis more easily through skin appendages. Microemulsions reduce the greasiness of oily drugs, making topical application more convenient. As an example, by weight, the oil phase typically comprises 5–6 parts, and the emulsifier typically comprises 7–9 parts, which further facilitates the stable and abundant presence of the oil phase in the aqueous phase.
[0018] The cinnamaldehyde-octadecylamine complex in the oil phase is a product of the reaction between cinnamaldehyde and octadecylamine. This complex masks the molecular structure of cinnamaldehyde, improving its stability. Furthermore, during use, the cinnamaldehyde-octadecylamine complex reverts to cinnamaldehyde, retaining its therapeutic effect. The paeonol-octadecylamine covalently coupled compound is a product of the covalent interaction between the amino group in octadecylamine and the phenolic hydroxyl group in the paeonol structure. This prevents the oxidation of the phenolic hydroxyl group in the paeonol structure, improving its stability. Therefore, the cinnamaldehyde-octadecylamine complex and the paeonol-octadecylamine covalently coupled compound in the oil phase retain the therapeutic effects of cinnamaldehyde and paeonol while exhibiting better stability. When used in skin antibacterial and repairing lotions, they effectively improve skin health and enhance the treatment effect on acne. In addition, to enhance the therapeutic effect of antibacterial and repairing skin lotion, 0.5 to 0.7 parts by weight of glycyrrhizin can generally be added. Glycyrrhizin also has a good therapeutic effect on acne. However, since glycyrrhizin has good water solubility and is relatively stable, it is generally not specially treated.
[0019] Furthermore, in the embodiments of this application, in order to enable the emulsifier to have a good emulsifying effect, the emulsifier generally includes one or more of polyethylene glycol 12-hydroxystearate, caprylic / capric triglyceride, diethylene glycol monoethyl ether, polyethylene glycol 400, and octadecylamine.
[0020] This application also provides a method for preparing a skin antibacterial repair emulsion, which includes the following steps: mixing an oil phase, an aqueous phase and an emulsifier and stirring, so that the oil phase is dispersed in the aqueous phase in the form of droplets under the action of the emulsifier, and the droplet size does not exceed 200 nm; wherein the components of the oil phase include at least one of cinnamaldehyde octadecylamine complex, paeonol octadecylamine covalently coupled compound and asiatic acid.
[0021] In the preparation process of the embodiments of this application, the cinnamaldehyde-octadecylamine complex and the paeonol-octadecylamine covalently coupled compound require special treatment to obtain. The following is a detailed description of the preparation process for these two substances:
[0022] The preparation steps of the cinnamaldehyde-octadecylamine complex include: mixing cinnamaldehyde and octadecylamine in solution to allow the cinnamaldehyde and octadecylamine to react, with the reaction temperature generally controlled at 40–80°C.
[0023] In the above steps, octadecylamine reacts with cinnamaldehyde to form a stable cinnamaldehyde-octadecylamine complex. In order to ensure that cinnamaldehyde can react fully, the reaction time generally lasts for 1 to 8 hours, and the molar ratio of cinnamaldehyde to octadecylamine is generally 1:1 to 1:2.
[0024] In addition, the solution state can generally be provided by ethanol; that is, "mixing cinnamaldehyde and octadecylamine in solution state" means dissolving cinnamaldehyde and octadecylamine in ethanol. Of course, in some other embodiments, other organic solvents can be used instead of ethanol, which will not be elaborated here.
[0025] The preparation steps of the paeonol-octadecylamine covalent coupler include: mixing paeonol and octadecylamine in solution and coupling paeonol and octadecylamine at a coupling temperature of 10–40 °C.
[0026] In the above steps, the amino group in octadecylamine couples with the phenolic hydroxyl group in paeonol to form a stable paeonol-octadecylamine covalent couple. In order to ensure that paeonol can fully couple with octadecylamine, the coupling time generally lasts for 12 to 30 hours, and the molar ratio of paeonol to octadecylamine is generally 1:1 to 1:2.
[0027] Similarly, in the formation of the paeonol-octadecylamine covalently coupled compound, the solution state can generally be provided by ethanol. In other embodiments, other common organic solvents can be used instead of ethanol.
[0028] The features and performance of this application will be further described in detail below with reference to the embodiments.
[0029] Example 1
[0030] This embodiment provides a cinnamaldehyde-octadecylamine complex, the preparation steps of which are as follows:
[0031] Weigh 0.49 g of cinnamaldehyde and 1.0 g of octadecylamine, place them in a 250 ml round-bottom flask, add 100 ml of anhydrous ethanol, heat under reflux for 4 h, cool naturally, and remove the ethanol by rotary evaporation at 40 °C to obtain the cinnamaldehyde-octadecylamine complex.
[0032] In the embodiments of this application, the molar ratio of cinnamaldehyde and octadecylamine is approximately 1:1.
[0033] Example 2
[0034] This embodiment provides a paeonol-octadecylamine covalently coupled compound, the preparation steps of which are as follows:
[0035] Weigh 0.62 g of paeonol and 1.0 g of octadecylamine, place them in a 250 ml round-bottom flask, add 100 ml of anhydrous ethanol, stir at room temperature for 24 h, and remove the ethanol by rotary evaporation at 40 °C to obtain the paeonol-octadecylamine covalently coupled compound.
[0036] In the embodiments of this application, the molar ratio of paeonol and octadecylamine is approximately 1:1.
[0037] Example 3
[0038] This embodiment provides a skin antibacterial and repairing lotion, the preparation steps of which are as follows:
[0039] (1) Take 0.3g of polyethylene glycol 12-hydroxy stearate, 0.05g of caprylic / capric triglyceride, 0.204g of octadecylamine, 0.2g of diethylene glycol monoethyl ether, and 0.1g of polyethylene glycol 400 and mix them evenly as emulsifiers. Keep them warm in a water bath at 50°C for later use.
[0040] (2) Take 0.15g of cinnamaldehyde octadecylamine complex from Example 1, 0.13g of paeonol octadecylamine covalently coupled compound from Example 2, and 0.1g of asiatic acid and add them to 0.2g of isopropyl myristate. Stir and mix evenly to obtain the oil phase, and keep it warm in a water bath at 50°C for later use.
[0041] (3) Mix the emulsifier in step (1) and the oil phase in step (2) evenly and stir, and add 50°C pure water and 0.06g glycyrrhizin, and continue stirring to obtain the skin antibacterial repair emulsion.
[0042] According to dynamic light scattering method, the droplet size in this embodiment is 122±11 nm.
[0043] Comparative Example 1
[0044] This comparative example provides a skin antibacterial repair lotion, whose preparation steps differ from those of Example 3 mainly in the following ways:
[0045] In step (2), 0.05g of cinnamaldehyde, 0.05g of paeonol and 0.1g of asiatic acid are added to 0.2g of isopropyl myristate, stirred and mixed evenly to obtain the oil phase, and kept warm in a water bath at 50℃ for later use.
[0046] According to dynamic light scattering method, the droplet size in this embodiment is 116±13nm.
[0047] Application examples
[0048] Stability test
[0049] The contents of cinnamaldehyde and paeonol in the skin antibacterial repair emulsions of Example 3 and Comparative Example 1 were determined by high performance liquid chromatography.
[0050] The determination conditions for cinnamaldehyde were as follows: chromatographic column: C18 column (4.6 mm × 250 mm, 5 μm); mobile phase: acetonitrile-0.1% phosphoric acid (55:45); detection wavelength: 290 nm; flow rate: 1.0 mL / min. -1 Column temperature 30℃; injection volume 10μL.
[0051] The determination conditions for paeonol were as follows: chromatographic column: C18 column (4.6 mm × 250 mm, 5 μm); mobile phase: methanol-water (70:30); detection wavelength: 274 nm; flow rate: 1.0 mL / min. -1 Column temperature 30℃; injection volume 10μL.
[0052] The stability of the skin antibacterial repair emulsions of Example 3 and Comparative Example 1 under strong light irradiation of 4500±500 lux was investigated. The specific method is as follows: The skin antibacterial repair emulsions of Example 3 and Comparative Example 1 were respectively filled into vials, sealed, and placed in a strong light incubator at 4500±500 lux. Samples were taken at 0, 1, 2, 5, and 10 days to measure the changes in the content of cinnamaldehyde and paeonol. The results are shown in Table 1.
[0053] Table 1. Stability test results
[0054]
[0055] The results show that, compared with Comparative Example 1, cinnamaldehyde and paeonol exhibit higher stability in Example 3.
[0056] Determination of Minimum Inhibitory Concentration (MIC) of Bacteria
[0057] The bacteria were activated in ordinary broth medium and cultured to a concentration of 1×10⁻⁶. 8 CFU / mL, diluted 1000 times with culture medium. A two-fold dilution method was used: 180 μL of the diluted bacterial solution was added to one well of a 96-well microplate, and 100 μL of the bacterial solution was added to the remaining wells. Then, 20 μL of the skin antibacterial repair emulsion to be tested was added to well 1. After mixing the solution in well 1 with a microsyringe, 100 μL was added to well 2. After mixing the solution in well 2, 100 μL was added to well 3. This process was repeated until well 10. Well 11 served as a negative control.
[0058] The skin antibacterial repair lotion to be tested, provided by Example 3, is referred to as the experimental group, and the skin antibacterial repair lotion to be tested, provided by Comparative Example 1, is referred to as the control group. The experimental group and the control group were repeated 3 times each, and the average value of each group was taken. The results are shown in Table 2.
[0059] Table 2 Results of bacterial MIC determination
[0060]
[0061] The results show that, under the same cinnamaldehyde concentration, the minimum inhibitory concentration of the skin antibacterial repair emulsion in Example 3 against various bacteria was significantly lower than that in Comparative Example 1, indicating that the microemulsion of the composite component with octadecylamine as a stabilizer has a better antibacterial effect.
[0062] Determination of fungal MIC
[0063] The subjects were divided into an experimental group and a control group. The experimental group used the skin antibacterial repair emulsion prepared in Example 3 (with a cinnamaldehyde content of 2 mg / ml), while the control group used the skin antibacterial repair emulsion prepared in Comparative Example 1 (with a cinnamaldehyde content of 2 mg / ml). Candida albicans, Penicillium, and Saccharomyces cerevisiae were diluted with sterile physiological saline to a concentration of 5 × 10⁻⁶. 3 The cfu / mL concentration was determined according to the method for determining the minimum inhibitory concentration of bacteria, and the results are shown in Table 3.
[0064] Table 3 Results of fungal MIC determination
[0065]
[0066] As shown in the table, based on the concentration of cinnamaldehyde, the minimum inhibitory concentration of the skin antibacterial repair lotion in Example 3 against various fungi is significantly lower than that in Comparative Example 1, indicating that the skin antibacterial repair lotion in Example 3 has a better antifungal effect.
[0067] Acne repair effect test
[0068] Twelve volunteers with acne were included in the study. During the two-week trial, no cosmetics, medications, or health supplements that could affect the results were used. Volunteers applied the antibacterial and repairing skin lotion from Example 3 to the affected areas morning and evening for two consecutive months. The anti-acne repair effect was observed by taking photos on day 0, day 30, and day 60. The results are shown in Table 4.
[0069] Table 4. Repair effects of volunteers applying the product for different durations.
[0070]
[0071] +++: Significant effect; +: Effective; -: No effect
[0072] As shown in Table 4, the volunteers experienced significant therapeutic effects after applying the antibacterial and repairing emulsion from Example 3.
[0073] The applicant also provided images showing changes in acne on a patient's face, such as... Figure 1 As shown.
[0074] As shown in the figure, with the use of the antibacterial and repairing skin lotion, the severity of acne on the patient's face gradually decreased.
[0075] The above are merely embodiments of this application and are not intended to limit the scope of protection of this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the scope of protection of this application.
Claims
1. A skin antibacterial and repairing lotion, characterized in that, Its components include an oil phase, an aqueous phase, and an emulsifier, and the components of the oil phase are dispersed in the aqueous phase in the form of droplets under the action of the emulsifier, wherein the droplet size does not exceed 200 nm; The components of the oil phase include cinnamaldehyde octadecylamine complex, paeonol octadecylamine covalent coupler and asiatic acid; The emulsifiers include polyethylene glycol 12-hydroxystearate, caprylic / capric triglyceride, polyethylene glycol 400, and octadecylamine; The preparation of the cinnamaldehyde-octadecylamine complex includes the following steps: Cinnamaldehyde and octadecylamine are mixed in solution and reacted at a temperature of 40–80°C for 1–8 hours. The preparation of the paeonol-octadecylamine covalently coupled compound includes the following steps: Paeonol and octadecylamine are mixed in solution and coupled at a temperature of 10–40°C for 12–30 h.
2. The skin antibacterial and repairing lotion according to claim 1, characterized in that, The oil phase comprises 5 to 6 parts by weight, and the emulsifier comprises 7 to 9 parts by weight.
3. The skin antibacterial and repairing lotion according to claim 1, characterized in that, The skin antibacterial repair lotion also includes 0.5 to 0.7 parts by weight of glycyrrhizin.
4. A method for preparing the skin antibacterial and repairing emulsion according to claim 1, characterized in that, It includes the following steps: The oil phase, aqueous phase and emulsifier are mixed and stirred so that the oil phase is dispersed in the aqueous phase in the form of droplets under the action of the emulsifier, and the droplet size does not exceed 200 nm. The components of the oil phase include cinnamaldehyde octadecylamine complex, paeonol octadecylamine covalently coupled compound, and asiatic acid; The preparation of the cinnamaldehyde-octadecylamine complex includes the following steps: Cinnamaldehyde and octadecylamine are mixed in solution and reacted at a temperature of 40–80°C for 1–8 hours. The preparation of the paeonol-octadecylamine covalently coupled compound includes the following steps: Paeonol and octadecylamine are mixed in solution and coupled at a temperature of 10–40°C for 12–30 h.
5. The method for preparing the skin antibacterial and repairing emulsion according to claim 4, characterized in that, When preparing the cinnamaldehyde-octadecylamine complex, the molar ratio of cinnamaldehyde to octadecylamine is 1:1 to 1:
2.
6. The method for preparing the skin antibacterial and repairing emulsion according to claim 5, characterized in that, When preparing the paeonol-octadecylamine covalent couple, the molar ratio of paeonol to octadecylamine is 1:1 to 1:2.