High-permeability inclusion for relieving skin redness, heat and pain, preparation method therefor and use thereof

Abstract

A high-permeability inclusion for relieving skin redness, heat and pain, a preparation method therefor, and a use thereof. The inclusion comprises a capsule shell and capsule content encapsulated in an inner cavity of the capsule shell; the capsule shell comprises a nonionic surfactant, a co-surfactant, cholesterol, 4-tert-butyl cyclohexanol, a saffron extract and water; the capsule content comprises a Tephrosia purpurea seed extract and a Kadsura longepedunculata extract; in terms of parts by mass, the contents of the components in the wrapping body are as follows: a total mass of the nonionic surfactant, co-surfactant and cholesterol is 1.6-16.5 parts; a total mass of the 4-tert-butyl cyclohexanol, saffron extract, Tephrosia purpurea seed extract and Kadsura longepedunculata extract is 0.4-10 parts; and water is 0.2-4 parts. The inclusion has good permeability and can achieve instant and long-lasting effects in improving redness, heat and pain.

Description

A high-permeability inclusion for relieving skin redness, heat and pain, and its preparation method and application Technical Field

[0001] The present invention belongs to the field of cosmetics, and in particular relates to a high-permeability inclusion for relieving skin redness, heat and pain, and a preparation method and application thereof. Background Art

[0002] Sensitive skin (SS) is defined by characteristic skin perceptions, including subjective symptoms such as tightness, stinging, burning, and itching. The skin may appear normal or be accompanied by lesions such as erythema, scaling, and capillary dilation. In severe cases, inflammatory reactions and rashes may occur. With the development of industrialization and the improvement of people's cognitive level, the incidence of sensitive skin is increasing worldwide. Large-scale surveys in multiple countries have shown that the global prevalence of sensitive skin exceeds 40%. In my country, the prevalence of sensitive skin is over 38%, and the number of people with sensitive skin is increasing year by year. Therefore, sensitive skin has become a social problem that needs to be urgently addressed.

[0003] The mechanism of sensitive skin is currently unclear, but it is clear that it results from a combination of factors. Common causes include the following four main categories: ① Skin factors: disrupted skin barrier, skin nerve disorders, skin immune imbalance, and skin vasodilation; ② Environmental factors: pollutants, climate, and UV exposure; ③ Lifestyle factors: cosmetic use, diet, and alcohol intake; and ④ Endogenous factors: hormone levels and stress. Currently, sensitive skin types can be broadly categorized into the following three types: ① Barrier-impaired: dry, flaky skin with a high transient end-expiratory weight (TEWL); ② Immune-inflammatory: normal barrier function but inflammation and redness; and ③ Neurosensitivity: normal barrier function and no inflammation, but overexpression of the transient receptor potential vanilloid receptor 1 (TRPV1) receptor, a heat-pain sensor, causes neurological tingling, burning, and redness. Regardless of the classification, sensitive skin is inextricably linked to the barrier, inflammation, overexpression of nerves, and external environmental stressors. These factors often reinforce each other, resulting in persistent redness, heat, and pain, making sensitive skin difficult to cure.

[0004] Currently, soothing products available on the market have the following shortcomings: ① They only target a single symptom of redness, heat or pain, and cannot take all of them into account and be effective at the same time; ② The discomfort caused by sensitive skin, such as redness, heat, and pain, is a major source of trouble for consumers. Most products cannot immediately suppress the discomfort, resulting in a poor user experience; ③ The more active the raw materials, the more likely they are to change color, change taste, and become inactive, making it difficult to achieve good compatibility after adding them to the formula; ④ Sensitive skin involves not only the epidermis, but also the dermis. Due to the existence of the skin barrier, active ingredients have difficulty penetrating into the target layer deep in the skin, resulting in poor results.

[0005] Summary of the Invention

[0006] The purpose of the present invention is to overcome the problems existing in the above-mentioned prior art and provide a high-permeability inclusion for relieving redness, heat and pain of the skin, which can achieve immediate relief for sensitive skin and long-term improvement of redness, heat and pain, as well as a preparation method and application thereof.

[0007] The present invention is achieved through the following technical solutions:

[0008] The present invention provides a highly permeable inclusion for relieving skin redness, heat, and pain, the inclusion comprising a capsule shell and an inclusion enclosed in the inner cavity of the capsule shell;

[0009] The capsule shell comprises a nonionic surfactant, a cosurfactant, cholesterol, 4-tert-butyl cyclohexanol, saffron extract and water;

[0010] The contents of the capsule include Glycyrrhiza uralensis seed extract and Schisandra chinensis chinensis extract;

[0011] The contents of the components in the inclusions are as follows:

[0012] The total weight of the nonionic surfactant, cosurfactant and cholesterol is 1.6-16.5 parts;

[0013] The total weight of 4-tert-butyl cyclohexanol, crocus extract, ginkgo seed extract and Schisandra chinensis extract is 0.4-10 parts; and water is 0.2-4 parts.

[0014] The high permeability inclusions of the present invention contain a variety of active ingredients compounded and formed into a vesicle structure, so that the inclusions have good skin applicability and permeability, can relatively comprehensively achieve the effect of immediate relief of sensitive skin and long-term improvement of redness, heat and pain, and have good anti-inflammatory and skin barrier repair effects. The 4-tert-butyl cyclohexanol in the inclusions of the present invention is an inhibitor of transient receptor potential vanilloid receptor 1 (TRPV1), which can reduce the flow of calcium ions through TRPV1, quickly relieve the neurosensory overreaction of sensitive skin, significantly reduce the burning and tingling sensations, and reduce sensitive symptoms. The main component of saffron extract is glycosylated flavonoids, which are agonists of cannabinoid type II receptors (CB2). By activating CB2, it can weaken the activation of TRPV1 and inhibit the inflammatory response, promote the release of "β-endorphin", have an analgesic effect, and have a significant barrier repair effect, which can improve the discomfort symptoms of sensitive skin. Glycine max seed extract promotes the production of beta-endorphin, a neurosoothing peptide, activating the expression of stress-resistant genes in skin cells, significantly inhibiting skin irritation caused by external stress. Schisandra chinensis extract has dual effects of soothing irritation and evens skin tone. By regulating nonspecific vascular and neurological inflammation, it reduces neuroinflammation and vasodilation, reduces redness, and soothes sensitive skin. It also restricts the spread of pigmentation caused by ultraviolet rays and other factors, evens out skin tone. By combining 4-tert-butylcyclohexanol, crocus extract, Glycine max seed extract, and Schisandra chinensis extract as active ingredients, the 4-tert-butylcyclohexanol and crocus extract, present in the capsule structure, are preferentially released, providing immediate and long-lasting relief. It inhibits the release of inflammatory factors, comprehensively soothes skin irritation, improves redness and inflammation, and enhances skin tolerance.

[0015] As a preferred embodiment of the highly permeable inclusions for soothing skin redness, heat, and pain described herein, the mass ratio of 4-tert-butyl cyclohexanol, crocus sativus extract, ginkgo biloba seed extract, and Schisandra chinensis extract is (0.1-3):(0.1-2):(0.1-2):(0.1-3). Research has found that the four active ingredients, when combined in this ratio, exhibit enhanced soothing effects on redness, heat, and pain.

[0016] Preferably, the mass ratio of the 4-tert-butyl cyclohexanol, crocus sativus extract, ginkgo biloba seed extract and schisandra chinensis extract is (0.5-1): (0.5-1): (0.1-1): (0.5-1).

[0017] More preferably, the mass ratio of 4-tert-butyl cyclohexanol, crocus extract, ginkgo biloba seed extract, and schisandra chinensis extract is 1:0.5:0.75:0.5. When these four active ingredients are combined in this specific ratio, they have a better effect in soothing skin redness, heat, and pain, and a higher profit.

[0018] As a preferred embodiment of the highly permeable inclusions for soothing skin redness, heat, and pain of the present invention, the mass ratio of the nonionic surfactant, co-surfactant, and cholesterol is (1-12):(0.1-1.5):(0.5-3). With this ratio, the resulting vesicle inclusions are able to better encapsulate the active ingredient, resulting in greater stability of the highly permeable inclusions.

[0019] More preferably, the mass ratio of the nonionic surfactant, the cosurfactant, and the cholesterol is 6:0.75:1.5. In this specific ratio, the obtained vesicle inclusions can have a better embedding effect and the obtained high permeability inclusions have better stability.

[0020] As a preferred embodiment of the highly permeable inclusion for relieving skin redness, heat, and pain of the present invention, at least one of the following conditions is met:

[0021] (1-1) The nonionic surfactant includes at least one of monoglyceride, propylene glycol fatty acid ester, polyglyceryl-10 oleate, polyglyceryl-10 diisostearate, polyglyceryl-3 methylglucose distearate, polyglyceryl-10 laurate, glyceryl oleate citrate, polyglyceryl-2 dipolyhydroxystearate, cetearyl alcohol, and cetearyl glucoside;

[0022] (1-2) The co-surfactant includes at least one of polyethylene glycol-400, polyethylene glycol-600, caprylic / capric triglyceride, PEG-40 hydrogenated castor oil, and PEG-60 hydrogenated castor oil.

[0023] Preferably, at least one of the following is met:

[0024] (2-1) The nonionic surfactant is monoglyceride of fatty acid, cetearyl alcohol and polyglyceryl-10 oleate;

[0025] (2-2) The co-surfactant is PEG-40 hydrogenated castor oil.

[0026] Furthermore, in the nonionic surfactant, the mass ratio of the monoglyceride, polyglycerol-10 oleate, and cetearyl alcohol is 3:2:1.

[0027] Another object of the present invention is to provide a method for preparing the highly permeable inclusions for relieving skin redness, heat, and pain, comprising the following steps:

[0028] S1. The 4-tert-butyl cyclohexanol, saffron extract, nonionic surfactant, and cosurfactant were stirred under heating conditions until completely mixed, and cooled to obtain a nonionic surfactant mixture;

[0029] S2. The nonionic surfactant mixture obtained in step S1 is mixed with water and cholesterol, heated, homogenized, and then cooled to obtain a capsule material;

[0030] S3. Add the Glycine max seed extract and Schisandra chinensis chinensis extract to the capsule material obtained in step S2, and homogenize under high pressure to obtain the highly permeable inclusions that relieve skin redness, heat, and pain.

[0031] The preparation method of the high-permeability inclusions of the present invention is simple, easy, highly stable, and suitable for large-scale industrial production. Furthermore, the present invention further uses a nonionic surfactant to encapsulate 4-tert-butyl cyclohexanol and crocus extract in the capsule shell layer, and encapsulates the ginkgo seed extract and the schisandra chinensis extract in the aqueous cavity within the capsule. Upon contact with the skin, the 4-tert-butyl cyclohexanol and the crocus extract are preferentially released, acting on transient receptor potential vanilloid receptor 1 (TRPV1) and cannabinoid type II receptor (CB2), instantly inhibiting the transmission of related redness, heat, and pain sensations. Subsequently, the ginkgo seed extract and the schisandra chinensis extract are targeted and delivered to the site of action, continuously soothing the skin's discomfort, achieving better immediate and long-lasting soothing effects.

[0032] As a preferred embodiment of the method for preparing the highly permeable inclusions for relieving skin redness, heat, and pain of the present invention, at least one of the following conditions is met:

[0033] (3-1) In step S1, the heating temperature is 60°C-70°C;

[0034] (3-2) In step S2, the heating temperature is 70°C-80°C, and the speed during homogenization is 1500r / min-2500r / min;

[0035] (3-3) In step S3, the pressure of the high-pressure homogenization is 500 bar-800 bar, the speed is 1000 r / min-2000 r / min, and the number of times is 3-5 times.

[0036] Another object of the present invention is to provide the use of the highly permeable inclusions for relieving skin redness, heat and pain in cosmetics.

[0037] The high-permeability inclusions of the present invention have comprehensive immediate and long-lasting effects of relieving redness, heat, and pain of the skin. Due to the formation of a vesicle encapsulation structure, the size can reach the micron level, and it has good permeability, which is conducive to skin absorption. It can be widely used in cosmetics, including but not limited to lotions, emulsions, creams, facial masks, essences, sprays, sunscreens, sunscreen sprays, sunscreen milks and other skin care products as well as various types of makeup.

[0038] Another object of the present invention is to provide an emulsion comprising the highly permeable inclusions for relieving skin redness, heat and pain of the present invention, wherein the mass percentage of the highly permeable inclusions for relieving skin redness, heat and pain in the emulsion is 3.2%-27%.

[0039] By applying the high-permeability inclusions of the present invention to lotions, a soothing lotion with immediate and long-lasting effects of soothing skin redness, heat and pain can be obtained.

[0040] Preferably, the emulsion comprises the following components in percentage by mass: 3.2%-27% of the high-permeability inclusions for relieving skin redness, heat and pain according to the present invention, 0.1%-0.5% of a thickener, 4%-20% of a moisturizer, 0.1%-10% of an emulsifier, 0.5%-5% of a preservative, 0.05%-0.2% of a fragrance, 0.05-0.1% of a pH adjuster, and the balance being water.

[0041] Compared with the prior art, the present invention has the following beneficial effects:

[0042] (1) The present invention scientifically compounds 4-tert-butyl cyclohexanol, saffron extract, ginkgo seed extract and Schisandra chinensis extract to form a comprehensive high-permeability inclusion that relieves skin redness, heat and pain. 4-tert-butyl cyclohexanol, as a TRPV1 antagonist, can reduce the heat and pain caused by external environmental stimulation. Saffron extract, as a CB2 activator, can provide continuous analgesia. Ginkgo seed extract generates a "natural analgesic" β-endorphin for the discomfort caused by external pressure. Schisandra chinensis can inhibit vascular inflammation and vasodilation, and correct red blood streaks. At the same time, the high-permeability inclusion also has good anti-inflammatory and skin barrier repair effects, which can comprehensively relieve stimulation and improve skin tolerance.

[0043] (2) The preparation method of the present invention further uses a non-ionic surfactant to encapsulate 4-tert-butyl cyclohexanol and saffron extract in the capsule shell layer, and encapsulates the ginkgo seed extract and the schisandra chinensis extract in the aqueous cavity inside the capsule. After contacting the skin, 4-tert-butyl cyclohexanol and the saffron extract are preferentially released, acting on the transient receptor potential vanilloid receptor 1 (TRPV1) and the cannabinoid type II receptor (CB2), which can immediately inhibit the conduction of related redness, heat, and pain sensations, instantly soothe and fade redness, and then the ginkgo seed extract and the schisandra chinensis extract are targeted and delivered to the site of action, continuously soothing the discomfort of the skin. Compared with liposomes prepared from cholesterol and phospholipids, the obtained vesicle inclusions have strong stability.

[0044] (3) The highly permeable inclusions of the present invention can encapsulate multiple soothing active ingredients together to produce a beneficial effect. When used as a drug reservoir, the vesicle inclusions have a certain viscosity, which can prolong the drug's retention time in the skin. The non-ionic surfactant in the vesicle inclusions can relax the cells of the stratum corneum and enhance the drug's ability to penetrate the epidermis and dermis. Compared with the use of penetration enhancers, they do not cause irritation or other damage to tissues, and are low-cost and suitable for industrial production. DETAILED DESCRIPTION

[0045] To better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments. Those skilled in the art should understand that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0046] Unless otherwise specified, the experimental methods used in the examples are conventional methods. Materials and reagents used are commercially available unless otherwise specified. Crocus sativus extract was obtained from ID BIO (France), Glycine max seed extract was obtained from Givaudan (Switzerland), and Schisandra chinensis extract was obtained from Shanghai Boshuo Industrial Co., Ltd.

[0047] The inclusions for relieving skin redness, heat, and pain of Examples 1 to 8 and the inclusions of Comparative Examples 1 to 9 are made of the components in parts by mass shown in Table 1.

[0048] Table 1 Components by mass (parts)

[0049] The preparation methods of the highly permeable inclusions for relieving skin redness, heat, and pain in Examples 1 to 8 and Comparative Examples 1-2 and Comparative Examples 6-7 are as follows:

[0050] S1. 4-tert-butyl cyclohexanol, crocus sativus extract, monoglyceride, polyglyceryl-10 oleate, cetearyl alcohol, and PEG-40 hydrogenated castor oil were mixed and heated to 70°C, stirred at low speed until completely mixed, and cooled to room temperature to obtain a nonionic surfactant mixture;

[0051] S2. The nonionic surfactant mixture obtained in step S1 was heated to 80°C with deionized water and cholesterol, homogenized at a speed of 2500 r / min for 10 min, and cooled to room temperature to obtain a capsule material;

[0052] S3. Add the glycine max seed extract and the Schisandra chinensis chinensis extract to the capsule material obtained in step S2, and homogenize by microfluidization high pressure at a speed of 2000 r / min and a pressure of 800 bar for 5 times to obtain the highly permeable inclusions that relieve skin redness, heat, and pain.

[0053] Example 9

[0054] The only difference between Example 9 and Example 1 is that the nonionic surfactant is 3 parts of polyglyceryl-10 diisostearate, 2 parts of glyceryl oleate citrate, and 1 part of polyglyceryl-10 laurate, and the co-surface emulsifier is 0.75 parts of caprylic / capric triglyceride. The remaining ingredients and proportions are the same as in Example 1. In the preparation method, only the nonionic surfactant and co-surface emulsifier are replaced with the components of this example; the rest is the same as in Example 1, to obtain the inclusions of this example.

[0055] Comparative Example 3

[0056] The preparation method of the inclusion for relieving skin redness, heat and pain in Comparative Example 3 is as follows:

[0057] S1. 4-tert-Butyl cyclohexanol, crocus extract, lecithin, cholesterol, and an appropriate amount of anhydrous ethanol were added to a round-bottom flask and thoroughly diffused under ultrasonic conditions. The mixture was evaporated to dryness on a rotary evaporator at a temperature of 30-50°C and then dried in a vacuum drying oven to form a membrane-like capsule.

[0058] S2. The glycine max seed extract, the Schisandra chinensis chinensis extract, and PEG-40 hydrogenated castor oil were added to a round-bottom flask for hydration, and then diffused in a water bath using ultrasound. The mixture was homogenized using a microjet high-pressure homogenizer at a speed of 2000 r / min and a pressure of 800 bar. After impurities were removed, the inclusions of Comparative Example 3 were obtained.

[0059] Comparative Example 4

[0060] The inclusions of Comparative Example 4 have the same components and contents as the high-permeability inclusions of Example 1, but are prepared by different methods. In this comparative example, the inclusions of Comparative Example 4 are obtained by simply stirring and mixing the various components in the inclusions.

[0061] Comparative Example 5

[0062] The difference between Comparative Example 5 and Example 1 is the preparation method of the inclusions. The preparation method of the inclusions for relieving skin redness, heat, and pain in Comparative Example 5 is as follows:

[0063] S1. 4-tert-butyl cyclohexanol, monoglyceride, polyglyceryl-10 oleate, cetearyl alcohol and PEG-40 hydrogenated castor oil were mixed and heated to 70 ° C, stirred at low speed until completely mixed, and cooled to room temperature to obtain a nonionic surfactant mixture;

[0064] S2. The nonionic surfactant mixture obtained in step S1 was heated to 80°C with deionized water and cholesterol, homogenized at a speed of 2500 r / min for 10 min, and cooled to room temperature to obtain a capsule material;

[0065] S3. Add saffron extract, glycine max seed extract and Schisandra chinensis extract to the capsule material obtained in step S2, and homogenize by microjet high pressure at a speed of 2000 r / min and a pressure of 800 bar for 5 times to obtain the inclusion body that relieves skin redness, heat and pain.

[0066] In the preparation method of Comparative Example 8, the preparation parameters are the same as those of Example 1 except that no saffron extract is added.

[0067] In the preparation method of Comparative Example 9, the preparation parameters are the same as those of Example 1 except that 4-tert-butyl cyclohexanol is not added.

[0068] The inclusions of the examples and comparative examples were added to an emulsion to prepare an emulsion. The emulsion was prepared according to the weight percentage components in Table 2:

[0069] Table 2 Mass percentage of each component in the emulsion

[0070] The preparation method of the emulsion is as follows: the components of phase A are added to water in sequence, and after Carbopol 980 is fully swelled, the mixture is homogeneously mixed, and the mixture and phase B are heated separately, and the mixture is homogeneously mixed and emulsified at 80°C. Phase C is heated until the p-hydroxyacetophenone melts, and the mixture is added to the emulsion and stirred evenly. After the temperature drops to 40°C, phase D is added and stirred to form a uniform emulsion. Finally, arginine is added to adjust the pH to obtain the emulsion.

[0071] Effect Example 1: Stability Experiment

[0072] The emulsions obtained in Examples 1-9 and Comparative Examples 1-9 were subjected to stability tests. The test results are shown in Table 3.

[0073] Test method: Place the samples in a constant temperature device at 50℃, 40℃, 25℃, 5℃, and -8℃, as well as a UV light aging box for stability testing. Take out the samples on the 0th, 1st, 7th, 14th, 21st, and 30th day respectively to observe whether there are obvious abnormal changes in appearance such as discoloration, stratification, precipitation, and precipitation.

[0074] Table 3 Stability test results

[0075] As shown in Table 3, Examples 1 and 6 exhibit color changes under UV and high temperature conditions, but the changes are minor. Example 1 exhibits less color change at 50°C and 40°C than Example 6. Comparative Example 1 exhibits severe discoloration or instability under UV, 50°C, 40°C, and -8°C conditions, indicating that the shell components must be within a certain ratio to achieve optimal encapsulation and stability; excessive or insufficient amounts affect stability. Comparative Example 2 exhibits color changes under UV and high temperature conditions, but the changes are minor, and micro-stratification occurs at low temperatures, indicating that the amount of active ingredient also needs to be within an appropriate range to ensure good emulsion stability; excessive or insufficient amounts affect stability. Comparative Example 3 exhibits severe color changes under UV, 50°C, and 40°C conditions, and releases water after returning to 15°C, significantly altering stability. This demonstrates that the inclusions obtained by encapsulating the active ingredient in non-ionic vesicles of the present invention are more stable than those obtained by liposome encapsulation. In Comparative Example 4, simple mixing failed to form a good vesicle inclusion structure, resulting in extremely poor stability. In Comparative Example 6, stratification occurred under low temperature, high temperature and UV conditions, indicating that the capsule shell components have better packaging effect and stability only when they are within a certain ratio range.

[0076] Effect Example 2: Permeability and Irritation Relief Experiment

[0077] The capsaicin pathway on human skin can be activated by capsaicin, acidity (pH <6.05), and temperatures above 42°C. Zebrafish also have a capsaicin pathway, which is also activated at high temperatures, reaching its peak at 37°C or above, manifested by a significant increase in swimming speed. Therefore, zebrafish activated by high temperatures are very suitable for testing sting relief. Software is used to measure the movement distance of zebrafish embryos, compare the changes in movement distance of zebrafish embryos in the test substance treatment group and the model control group, and calculate the reduction rate of movement distance to evaluate the ability of raw materials or products to relieve irritation.

[0078] The inclusions of Examples 1-9 and the inclusions of Comparative Examples 1-9 were tested under the following conditions.

[0079] Sample Preparation: The inclusions from Examples 1-9 and Comparative Examples 1-9 were mixed with water at a high-speed homogenizer at a mass ratio of 0.25%, then sonicated for 10 minutes. Fish embryo culture medium was then added to the desired concentration. After vortexing for 30 seconds, the mixture was centrifuged at 6500 rpm for 10 minutes. The supernatant was collected for testing. The test solution concentration of the test substance was designed to ensure a zebrafish embryo mortality rate of less than 10% (embryos without heartbeats were considered dead). Three concentration groups were tested.

[0080] Test steps: Select healthy zebrafish embryos that are 5 days old after fertilization. The test requires setting up a blank control group (fish embryo culture medium) and a sample group (test sample). Randomly select 16 fish embryos and transfer them to a 96-well plate. Each well contains one fish embryo and 0.2mL of the test solution. The blank control is pure zebrafish culture medium. Place it in a 28±1℃ incubator for 2h. Then transfer it to a zebrafish motion recorder and use infrared tracking software to record the swimming trajectory of each zebrafish embryo in a dark environment within 5 minutes. Replace the 0.18mL solution in each well with fish embryo culture medium, and then place it in a 28±1℃ incubator for 24±1h to calculate the survival rate of the fish embryos.

[0081] Data processing: The pixel intensity of each well was measured as the movement distance of each fish embryo.

[0082] Calculate the shortening rate of movement distance: shortening rate = (CT) / C×100%.

[0083] Where: T is the average movement distance of fish embryos in the test substance treatment group; C is the average movement distance of fish embryos in the blank control group; the results are shown in Table 4.

[0084] Table 4 Test results of movement distance shortening rate

[0085] The test results are shown in Table 4. The movement distance shortening rate of the blank group was 100%, the movement distance shortening rate of the zebrafish in the Example 1 group was 99.73%, and the movement distance shortening rate of the inclusions in Examples 1-9 was higher than that of the inclusions in Comparative Examples 1-9, indicating that the highly permeable inclusions of the present invention for soothing skin redness, heat, and pain have a strong soothing effect on TRPV1 and can reduce skin irritation.

[0086] The movement distance shortening rate of Comparative Example 1 and Comparative Example 6 is reduced, indicating that the capsule shell components need to be within a reasonable range in order for the inclusion body to have good permeability and soothing effect. The movement distance shortening rate of Comparative Example 2 and Comparative Example 7 is significantly reduced, indicating that the active ingredients need to be within an appropriate range in order for the inclusion body to have good permeability and soothing effect. The movement distance shortening rate of Comparative Example 4 is 32.47%, indicating that the soothing effect of 4-tert-butyl cyclohexanol, saffron extract, glycine max seed extract and Schisandra chinensis extract on zebrafish without encapsulation is weaker than that of the composition encapsulated by non-ionic vesicles. After encapsulation, the permeability of each active ingredient is increased, and more active ingredients can enter the skin, enhancing the soothing effect. The movement distance shortening rate of Comparative Example 5 is 42.36%, which is less than Example 1, indicating that 4-tert-butyl cyclohexanol and saffron extract co-encapsulated in the capsule shell layer can synergistically exert their instant soothing effect and better inhibit the redness, heat and pain of the skin caused by the activation of TRPV1. In Comparative Examples 8 and 9, although the amounts of active ingredients are the same, the four components are not compounded, and the synergistic effect between the components is weakened, resulting in a poorer soothing effect of the inclusions.

[0087] Effect Example 3: Instant soothing and redness-reducing effect experiment

[0088] The emulsions obtained in Examples 1 to 9 and Comparative Examples 1 to 9 were subjected to instant soothing and redness-removing efficacy tests under the following conditions. The results are shown in Table 5.

[0089] On the day of the visit, 72 volunteers were not allowed to apply any products to the test area. After washing their arms, they were asked to sit quietly in an air-conditioned room with a temperature of 21±1℃ and a humidity of 50±10% for 20 minutes. They were randomly divided into 9 groups, with 8 people in each group. Two 10cm thick spots were selected on each of the volunteers' left and right forearms. 2 (2.5cm×4cm) area and marked it with a skin marker pen. Initial TEWL and a* value measurements were performed on selected arm areas using the TM Hex (Courage+Khazaka) and the Colorimeter CL400.

[0090] The test model uses a 3M medical tape tearing model: 3M medical PE tape is used to tear and damage the measurement area to establish a skin damage model. 30 minutes after the damage model is established, the TEWL value and a* value are measured. The difference between the TEWL value and a* value of different damaged areas of the hand is kept within ±3g / hm 2The test emulsions obtained in Examples 1 to 9 and Comparative Examples 1 to 9 were distributed to 9 groups of volunteers. Three areas were randomly selected for each volunteer and two test emulsions were used respectively. A blank emulsion was used in one area. TEWL and a* values ​​were measured for the test areas after 1 hour and 4 hours of product use. The immediate skin barrier repair ability of the two samples was represented by the change in TEWL value, and the immediate redness-removing effect was represented by the change in a* value. The formula is as follows:

[0091] Table 5 Instant soothing and redness fading effects of Examples and Comparative Examples

[0092] As can be seen from the data in Table 5, compared to Comparative Examples 1-9, Examples 1-9 showed significant improvements in both barrier damage and redness. The TEWL and a* value improvements over 4 hours in Example 1 were significantly better than those in Examples 2-6. In Comparative Examples 1 and 6, the poor ratio of the shell components resulted in reduced encapsulation and stability. In Comparative Examples 2 and 7, the poor ratio of the active ingredient resulted in reduced immediate soothing and redness-reducing effects. In Comparative Example 3, the use of lecithin to encapsulate the active ingredient resulted in poor inclusion stability. In Comparative Example 4, while the active ingredient was not encapsulated, while exhibiting some redness-reducing effect, the immediate soothing effect over 1 hour was poor. In Comparative Example 5, the saffron extract was not encapsulated in the shell, preventing its preferential release, resulting in poor immediate soothing effect. In Comparative Example 8, despite the same total amount of active ingredient, the absence of saffron extract resulted in poor soothing effect. In Comparative Example 9, although the total amount of active ingredients was the same, 4-tert-butyl cyclohexanol was not added, and the soothing effect was poor.

[0093] The data in Table 5 show that the high-permeability inclusions of the present invention have excellent immediate soothing and redness-reducing effects.

[0094] Effect example 4: Anti-inflammatory and soothing experiment

[0095] In vitro stimulants can activate Toll-like receptors (TLR-2 and TLR-4) on keratinocytes, leading to the activation of MAPK and NF-κB pathways. Subsequently, keratinocytes produce IL-1, IL-6, IL-8, TNF-α, and human HBD-2 (defensins), thereby inducing inflammation and causing skin discomfort. By using LPS-induced human keratinocytes HaCaT cells as an in vitro inflammatory cell model, the inflammatory factors IL-1α, IL-1β and TNF-α secreted in the cell supernatant were detected by ELISA kits to evaluate the anti-inflammatory effects of the inclusions of Examples 1-9 and Comparative Examples 1-9.

[0096] HaCaT cells were cultured at a density of 2.0-3.0×10 5Each well was inoculated with 1 mL of culture medium containing 0.3% test sample and 50 μg / mL LPS. The model group was treated with culture medium containing only 50 μg / mL LPS. The positive control was treated with 1 mL of culture medium containing 50 μg / mL dexamethasone and 50 μg / mL LPS. The blank negative control was treated with only 1 mL of culture medium. The cells were cultured for 24 h. The supernatant was collected by centrifugation and stored at -80°C. IL-1α, IL-8, and TNF-α cytokines were measured using ELISA kits as described. Signals were detected at a wavelength of 450 nm. The inflammatory factor content was expressed as the secretion amount of IL-1α, IL-1β, and TNF-α per mL of culture medium (pg). Table 6 shows three replicates for each test.

[0097] Table 6 Comparison of inflammatory factors in different samples (Mean±SD, n=3) Note: "*" indicates that the secretion of inflammatory factors in the sample is significantly different from that in the model group, P < 0.05.

[0098] As can be seen from the data in Table 6, compared with Comparative Examples 1-9, Examples 1-9 have stronger ability to inhibit the secretion of inflammatory factors, among which Example 1 has the best effect in inhibiting the secretion of inflammatory factors. Analysis of Comparative Examples 1, 6, and 3 shows that the poor ratio of the shell components and the use of lecithin for packaging both hinder the ability to inhibit the secretion of inflammatory factors; Analysis of Comparative Examples 2 and 7 shows that the poor ratio of the active ingredients will lead to a weakening of the ability of the inclusion body to relieve inflammation; and Comparative Example 4 does not encapsulate the active ingredients. Although it also has a certain inhibitory effect on inflammatory factors, it is still different from the examples; Comparative Example 5 does not encapsulate the saffron extract in the shell, which also has a certain impact on the inhibitory effect on inflammatory factors; Comparative Example 8 does not add saffron extract and Comparative Example 9 does not add 4-tert-butyl cyclohexanol, both of which lead to poor inhibitory effects on inflammatory factors.

[0099] Effect Example 5: Long-lasting relief experiment

[0100] The emulsions obtained in Example 1, Comparative Example 4, and Comparative Examples 8-9 were subjected to a long-term soothing test under the following conditions. The improvement effects on TEWL, redness, and lactic acid stinging are shown in Table 7.

[0101] Volunteer screening: Select volunteers aged 21-44 years, with no history of severe skin diseases, no history of cosmetic allergies, sensitive skin (capsaicin-positive), and transepidermal water loss TEWL 20g / m 2 h~30g / m 2 h, with 15 people in each group and 4 groups in total.

[0102] Test steps: Before using the sample, each volunteer uniformly cleansed their face with an amino acid cleanser, sat quietly in a constant temperature and humidity efficacy evaluation room for more than 5 minutes, and used a transepidermal moisture tester and a skin color tester to measure the facial TEWL value and a* value as D0 data. 50 μL of a 10% lactic acid aqueous solution was applied to the nasolabial groove of the subject's face. The subject was asked about his or her subjective symptoms at 2.5 minutes and 5 minutes, and scored according to a 4-point scale (0: no tingling, 1: mild tingling, 2: moderate tingling, and 3: severe tingling). The sum of the two scores was used as the scoring result of the lactic acid stinging test as D0 data. The emulsions of Example 1, Comparative Examples 4, and Comparative Examples 8-9 were used once in the morning and evening in the same amount. The facial TEWL, a* value, and lactic acid stimulation values ​​were measured after 14 days and 28 days, respectively. The changes in the values ​​were used to indicate the effects of the samples on skin physiological parameters.

[0103] Table 7 28-day long-term soothing efficacy test results

[0104] Compared with the comparative example, the emulsion of the embodiment can significantly improve the skin condition in the 28-day TEWL, a* value and lactic acid stinging test, and effectively relieve the redness, heat and pain of the skin.

[0105] Compared with the other examples, Example 1 achieved the best long-term soothing effect. As can be seen from the data in Table 7, in Comparative Example 4, the active ingredients were not encapsulated, resulting in decreased permeability and poor long-term soothing effect. In Comparative Example 8, although the total amount of active ingredients was the same, saffron extract was not added, resulting in reduced synergy between the active ingredients and poor long-term soothing effect. In Comparative Example 9, although the total amount of active ingredients was the same, 4-tert-butylcyclohexanol was not added, resulting in reduced synergy between the active ingredients and poor long-term soothing effect.

[0106] The data in Table 7 show that the inclusion composition encapsulated by non-ionic vesicles of the present invention can effectively relieve redness, heat and pain of the skin, and has a certain barrier repair effect.

[0107] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. An inclusion for relieving skin redness, heat and pain, characterized in that: The inclusion body comprises a capsule shell and capsule contents enclosed in the inner cavity of the capsule shell; The capsule shell comprises a nonionic surfactant, a co-surfactant, cholesterol, 4-tert-butyl cyclohexanol, saffron extract and water; The capsule contents include ginkgo seed extract and Schisandra chinensis chinensis extract; The content of each component in the inclusion is as follows: The sum of the mass of the nonionic surfactant, the co-surfactant and the cholesterol is 1.6-16.5 parts; The sum of the weight of 4-tert-butyl cyclohexanol, crocus extract, ginkgo seed extract and Schisandra chinensis extract is 0.4-10 parts; Water: 0.2-4 parts; The mass ratio of the nonionic surfactant, the co-surfactant and the cholesterol is (1-12): (0.1-1.5): (0.5-3); The mass ratio of the 4-tert-butyl cyclohexanol, saffron extract, ginkgo seed extract and Schisandra chinensis extract is (0.1-3): (0.1-2): (0.1-2): (0.1-3); The nonionic surfactant includes at least one of monoglycerol fatty acid ester, propylene glycol fatty acid ester, polyglyceryl-10 oleate, polyglyceryl-10 diisostearate, polyglyceryl-3 methyl glucose distearate, polyglyceryl-10 laurate, glyceryl oleate citrate, polyglyceryl-2 dipolyhydroxystearate, cetearyl alcohol, and cetearyl glucoside; The co-surfactant includes at least one of polyethylene glycol-400, polyethylene glycol-600, caprylic / capric triglyceride, PEG-40 hydrogenated castor oil, and PEG-60 hydrogenated castor oil.

2. The inclusion for relieving skin redness, heat and pain according to claim 1, characterized in that: The mass ratio of the 4-tert-butyl cyclohexanol, saffron extract, ginkgo seed extract and schisandra chinensis extract is (0.5-1): (0.5-1): (0.1-1): (0.5-1).

3. The inclusion for relieving skin redness, heat and pain according to claim 2, characterized in that: The mass ratio of the 4-tert-butyl cyclohexanol, saffron extract, ginkgo seed extract and Schisandra chinensis extract is 1:0.5:0.75:0.

5.

4. The inclusion for relieving skin redness, heat and pain according to claim 1, characterized in that: The mass ratio of the nonionic surfactant, the co-surfactant and cholesterol is 6:0.75:1.

5.

5. The inclusion for relieving skin redness, heat and pain according to claim 1, characterized in that: Satisfy at least one of the following: (2-1) The nonionic surfactant is monoglyceride, cetearyl alcohol and polyglyceryl-10 oleate; (2-2) The co-surfactant is PEG-40 hydrogenated castor oil.

6. The inclusion for relieving skin redness, heat and pain according to claim 5, characterized in that: The mass ratio of the monoglyceride, polyglycerol-10 oleate and cetearyl alcohol is 3:2:

1.

7. The method for preparing the inclusion for relieving skin redness, heat and pain according to any one of claims 1 to 6, characterized in that: The following steps are involved: S1. The 4-tert-butyl cyclohexanol, saffron extract, nonionic surfactant and co-surfactant are stirred under heating conditions until completely mixed, and cooled to obtain a nonionic surfactant mixture; S2. The nonionic surfactant mixture obtained in step S1 is mixed with water and cholesterol, heated, homogenized and then cooled to obtain a capsule material; S3. Add the Glycine max seed extract and Schisandra chinensis chinensis extract to the capsule material obtained in step S2, and homogenize under high pressure to obtain the inclusion body for relieving skin redness, heat and pain.

8. The method for preparing an inclusion for relieving skin redness, heat and pain according to claim 7, characterized in that: Satisfy at least one of the following: (3-1) In step S1, the heating temperature is 60°C-70°C; (3-2) In step S2, the heating temperature is 70°C-80°C, and the speed during homogenization is 1500r / min-2500r / min; (3-3) In step S3, the pressure of the high-pressure homogenization is 500 bar-800 bar, the rotation speed is 1000 r / min-2000 r / min, and the number of times is 3-5 times.

9. Use of the inclusion for relieving skin redness, heat and pain as claimed in any one of claims 1 to 6 in cosmetics.

10. An emulsion, characterized in that The lotion comprises the inclusions for relieving skin redness, heat and pain as claimed in any one of claims 1 to 6, and the mass percentage of the inclusions for relieving skin redness, heat and pain in the lotion is 3.2% to 27%.

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