Skin barrier repair compositions and uses thereof

Abstract

This application provides a skin barrier repair composition, comprising an intercellular lipid supplement, a stratum corneum repair agent, and an optional barrier function protectant. This application rationally combines multiple beneficial ingredients for skin barrier repair, resulting in a synergistic effect. Furthermore, this application co-contains these beneficial ingredients within a nanocarrier, thereby further enhancing the skin barrier repair function and broadening the application scope of the intercellular lipid supplement, stratum corneum repair agent, and barrier function protectant.

Description

[0001] This case is a divisional application of the application filed on December 15, 2022, entitled "Skin Barrier Repair Composition and Its Use Thereof", with application number 2022117014006. Technical Field

[0002] This application belongs to the field of cosmetic technology, specifically relating to a skin barrier repair composition and its use. Background Technology

[0003] As the largest organ in the human body, the skin serves as a bridge between the body and the external environment, and is the first line of defense against external damage. The skin barrier plays a vital role in protecting the body from mechanical damage, microbial invasion, chemical penetration, and preventing the loss of moisture and nutrients. Once the skin barrier is damaged, it leads to decreased water retention, reduced tolerance, and increased stimulation from external allergens and harmful substances. Pathogens can more easily penetrate the stratum corneum to reach deeper layers of the skin, thus increasing the incidence of skin diseases such as eczema and dermatitis. Furthermore, some skin diseases are accompanied by damage to the barrier structure and function, such as acne, seborrheic dermatitis, melasma, rosacea, and steroid-induced dermatitis. Without effective repair of the skin barrier structure and function, improvement of skin condition and skin diseases is impossible. The skin barrier function is crucial and vulnerable, and the barrier's self-repair process is slow, taking anywhere from 2-3 months to more than six months. Therefore, how to effectively repair the skin barrier has become one of the most pressing skin problems to be addressed.

[0004] The skin barrier can be viewed as a typical "brick wall structure," with the sebum film acting as the outer wall, the underlying "bricks" represented by stratum corneum cells, and intercellular lipids as the "mortar." These three elements are tightly bound together to form a complete skin barrier structure. The sebum film, located on the outermost layer of the epidermis, is composed of water and lipids secreted by sweat glands and transdermal fluids, providing the skin with moisture retention. Keratinocytes play a major role in the skin barrier function, preventing harmful external substances from invading the body. They mainly contain keratin and natural moisturizing factors. Intercellular lipids are important components for maintaining normal skin metabolism and moisture retention. They contain 50% ceramides, 25% cholesterol, 15% free fatty acids, and a small amount of phospholipids, forming a tightly stacked intercellular lipid matrix structure together with the stratum corneum.

[0005] While skin barrier repair products are available on the market, many fail to deliver satisfactory results for consumers. The main reasons include: inadequate formulation design and simplistic mechanisms of action. For example, some products focus solely on replenishing intercellular lipids or providing basic hydration, failing to fundamentally repair the skin barrier; some products may even damage the skin barrier themselves. Furthermore, many active ingredients that promote skin barrier repair are unstable, easily leading to oxidative denaturation or inactivation during storage and transportation when directly applied to cosmetics, significantly reducing their barrier repair effectiveness. More importantly, due to their inherent properties and the limitations of skin barrier function, these barrier repair ingredients often struggle to penetrate the stratum corneum and accumulate to effective concentrations within the skin barrier, greatly diminishing their actual repair efficacy. Summary of the Invention

[0006] To address the problems existing in the prior art, this application provides a skin barrier repair composition and its use.

[0007] Specifically, this application relates to the following aspects: 1. A skin barrier repair composition, characterized in that the skin barrier repair composition comprises an intercellular lipid supplement and a stratum corneum repair agent.

[0008] 2. The composition according to claim 1, characterized in that the intercellular lipid supplement comprises one or two of phytosphingosine and cholesterol; and the stratum corneum repair agent comprises one or two of hydrolyzed hyaluronic acid or its salt and tripeptide-1.

[0009] 3. The composition according to item 2, characterized in that the molecular weight of the hydrolyzed hyaluronic acid or its salt is less than 10 kDa, preferably 1 kDa-10 kDa.

[0010] 4. The composition according to any one of claims 1-3, characterized in that the composition further comprises a barrier function protectant.

[0011] 5. The composition according to claim 4, characterized in that the barrier function protectant comprises a hyaluronic acid substance, preferably, the hyaluronic acid substance comprises one or two of hyaluronic acid or its salt, acetylated hyaluronic acid or its salt. Preferably, the hyaluronic acid or its salt has a molecular weight of 100 kDa or more, more preferably 100 kDa-2000 kDa, and the acetylated hyaluronic acid or its salt has a molecular weight of 10 kDa-100 kDa.

[0012] 6. The composition according to any one of items 1-5, characterized in that the composition optionally further comprises one or more of the following: (1) The intercellular lipid supplement also includes one or two of ceramides and fatty acid triglycerides; (2) The stratum corneum repair agent also includes one or two of ectoine and β-glucan.

[0013] 7. The composition according to any one of items 1-6, characterized in that, based on the total mass of the skin barrier repair composition, the content of the intercellular lipid supplement is 0.1%-15%, preferably 1%-5%, and the content of the stratum corneum repair agent is 0.1%-15%, preferably 1%-5%.

[0014] 8. The composition according to any one of items 4-7, characterized in that, based on the total mass of the skin barrier repair composition, the content of the barrier function protectant is 0.1%-15%, preferably 0.1%-5%.

[0015] 9. The skin barrier repair composition according to any one of claims 1-8, characterized in that the composition further comprises an emulsifier and a co-emulsifier. Preferably, based on the total mass of the skin barrier repair composition, the content of the emulsifier is 1%-40%, and the content of the co-emulsifier is 1%-40%. Preferably, the emulsifier includes one or more of polyglycerol emulsifiers, alkyl glucoside emulsifiers, and lecithin emulsifiers, and the co-emulsifier includes one or two of polyether co-emulsifiers and polyol co-emulsifiers.

[0016] 10. Use of the skin barrier repair composition according to any one of items 1-9 in the preparation of cosmetics.

[0017] The beneficial effects obtained by this application include at least the following aspects: (1) This application rationally combines multiple functional ingredients that are beneficial to repairing the skin barrier, so that they produce a synergistic effect.

[0018] (2) Based on the synergistic effect of the above-mentioned active ingredients, this application further makes these active ingredients exist in the nanocarrier, which can effectively improve the solubility of the active ingredients while providing them with a stable storage space, and can also improve the skin permeability and retention properties of the active ingredients, improve their bioavailability, prolong the duration of action, thereby maximizing their original synergistic effect.

[0019] (3) The nanocarriers containing a variety of functional ingredients that are beneficial to repairing the skin barrier can be added as a raw material to other formulations, thereby broadening the application scope of the above-mentioned functional ingredients. Attached Figure Description

[0020] Figure 1This is the particle size distribution curve of the skin barrier repair composition described in Example 6 of this application.

[0021] Figure 2 The results show the skin penetration of the compound serum containing free Rhodamine B and Rhodamine B nanocarrier. Detailed Implementation

[0022] The present application is further illustrated below with reference to embodiments. It should be understood that the embodiments are only used to further illustrate and explain the present application and are not intended to limit the present application.

[0023] Unless otherwise defined, technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art. While similar or identical methods and materials may be applied in experimental or practical applications, materials and methods are described herein. In case of conflict, the definitions included herein shall prevail. Furthermore, materials, methods, and examples are for illustrative purposes only and are not intended to be limiting. The present application is further described below with reference to specific embodiments, but is not intended to limit the scope of the application.

[0024] This application provides a skin barrier repair composition comprising an intercellular lipid supplement and a stratum corneum repair agent.

[0025] In one specific embodiment, the intercellular lipid supplement includes one or both of phytosphingosine and cholesterol.

[0026] In one specific embodiment, the intercellular lipid supplement may further include one or both of ceramides and fatty acid triglycerides.

[0027] Among them, ceramides can be various ceramide subtypes and their combinations. Phytosphingosine is a precursor of ceramides and participates in ceramide production, and also promotes the differentiation of human epidermal keratinocytes.

[0028] In one specific embodiment, the intercellular lipid supplement includes at least phytosphingosine.

[0029] In one specific embodiment, the intercellular lipid supplement includes cholesterol.

[0030] In one specific embodiment, the intercellular lipid supplement includes phytosphingosine and cholesterol.

[0031] In one specific embodiment, the intercellular lipid supplement comprises a mixture of phytosphingosine and cholesterol mixed in any mass ratio.

[0032] In one specific embodiment, the stratum corneum repair agent comprises one or more of hydrolyzed hyaluronic acid or its salts, and tripeptide-1. The hydrolyzed hyaluronic acid or its salts may be, for example, hydrolyzed hyaluronic acid or its salts with a molecular weight of less than 10 kDa, such as 1 kDa, 1.5 kDa, 2 kDa, 2.5 kDa, 3 kDa, 3.5 kDa, 4 kDa, 4.5 kDa, 5 kDa, 5.5 kDa, 6 kDa, 6.5 kDa, 7 kDa, 7.5 kDa, 8 kDa, 8.5 kDa, 9 kDa, 9.5 kDa, 10 kDa, etc. Alternatively, it may be, for example, hydrolyzed hyaluronic acid or its salts with a molecular weight of 1 kDa to 10 kDa.

[0033] In one specific embodiment, the stratum corneum repair agent may further include one or both of ectoine and β-glucan.

[0034] In one specific embodiment, the stratum corneum repair agent includes at least hydrolyzed hyaluronic acid or its salt with a molecular weight of less than 10 kDa.

[0035] In one specific embodiment, the stratum corneum repair agent comprises tripeptide-1.

[0036] In one specific embodiment, the stratum corneum repair agent comprises hydrolyzed hyaluronic acid or its salt with a molecular weight of less than 10 kDa and tripeptide-1.

[0037] In one specific embodiment, the stratum corneum repair agent comprises a mixture of hydrolyzed hyaluronic acid or its salt with a molecular weight of less than 10 kDa and tripeptide-1 mixed in any mass ratio.

[0038] In one specific embodiment, based on the total mass of the skin barrier repair composition, the content of the intercellular lipid supplement is 0.1%-15%, for example, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, preferably 1-5%; the content of the stratum corneum repair agent is 0.1%-15%, for example, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, preferably 1-5%.

[0039] The compositions of this application may further include a barrier function protectant.

[0040] In one specific embodiment, the barrier function protectant includes hyaluronic acid-based substances, preferably, the hyaluronic acid-based substances include one or two of hyaluronic acid or its salts, acetylated hyaluronic acid or its salts.

[0041] The hyaluronic acid or its salt has a molecular weight of 100 kDa or higher, for example, 100 kDa, 1110 kDa, 120 kDa, 130 kDa, 140 kDa, 150 kDa, 160 kDa, 170 kDa, 180 kDa, 190 kDa, 200 kDa, 210 kDa, 250 kDa, 300 kDa, 350 kDa, 400 kDa, 450 kDa, 500 kDa, 550 kDa, 600 kDa, 650 kDa, 700 kDa, 750 kDa, 800 kDa, 850 kDa, 900 kDa, 1000 kDa, 1100 kDa, 1200 kDa, 1300 kDa, 1400 kDa, 1500 kDa, 1600 kDa, 1700 kDa, 1800 kDa, 1900 kDa, etc. kDa, 2000 kDa, etc., preferably 100 kDa-2000 kDa. The molecular weight of the acetylated hyaluronic acid or its salt is 10 kDa-100 kDa, for example, 10 kDa, 20 kDa, 30 kDa, 40 kDa, 50 kDa, 60 kDa, 70 kDa, 80 kDa, 90 kDa, 100 kDa.

[0042] In one specific embodiment, the barrier function protectant includes hyaluronic acid or a salt thereof, with a molecular weight of 100 kDa-2000 kDa.

[0043] In one specific embodiment, the barrier function protectant includes acetylated hyaluronic acid or a salt thereof, with a molecular weight of 10 kDa-100 kDa.

[0044] In one specific embodiment, the barrier function protectant comprises a mixture of hyaluronic acid or its salt, acetylated hyaluronic acid or its salt mixed in any mass ratio, wherein the molecular weight of the hyaluronic acid or its salt is 100 kDa-2000 kDa, and the molecular weight of the acetylated hyaluronic acid or its salt is 10 kDa-100 kDa.

[0045] In one specific embodiment, the content of the barrier function protectant is 0.1%-15% based on the total mass of the skin barrier repair composition, for example, it can be 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, preferably 0.1%-5%.

[0046] In one specific embodiment, the skin barrier repair composition is a nanocarrier, which includes the intercellular lipid supplement, the stratum corneum repair agent, and optionally a barrier function protectant. The nanocarrier is characterized by small particle size, large specific surface area, and high loading capacity. While effectively improving the solubility of the active ingredients, it provides a stable storage space, preventing unnecessary degradation or inactivation of the active ingredients before storage and use, thus facilitating a higher concentration of active substances in the skin barrier repair product. More importantly, the skin barrier repair nanocomposition is safe and non-irritating, improving the skin permeability and retention properties of the active ingredients. It promotes the penetration of the active ingredients into the stratum corneum and into the dermis, resulting in high concentration accumulation, long-term retention, sustained and controlled release, improved bioavailability, enhanced skin barrier repair and moisturizing effects, and prolonged duration of action.

[0047] In one specific embodiment, the nanocarrier further includes an emulsifier and a co-emulsifier.

[0048] The emulsifier includes one or more of polyglycerol emulsifiers, alkyl glucoside emulsifiers, and lecithin emulsifiers. For example, the emulsifier includes polyglycerol emulsifiers and alkyl glucoside emulsifiers; the emulsifier includes polyglycerol emulsifiers and lecithin emulsifiers; the emulsifier includes alkyl glucoside emulsifiers and lecithin emulsifiers; the emulsifier includes polyglycerol emulsifiers, alkyl glucoside emulsifiers, and lecithin emulsifiers.

[0049] Polyglycerol emulsifiers include polyglycerol-10 diisostearate, polyglycerol-10 oleate, polyglycerol-10 myristate, polyglycerol-4 oleate, polyglycerol-6 polyricinoleate, etc., preferably including polyglycerol-10 diisostearate, polyglycerol-10 oleate, or polyglycerol-10 myristate.

[0050] Glucoside emulsifiers include cocoyl glucoside, C12-16 alkyl glucoside, cetearyl glucoside, lauryl glucoside, etc., preferably cocoyl glucoside or C12-16 alkyl glucoside.

[0051] Lecithin emulsifiers include lecithin, hydrogenated lecithin, or hydroxylated lecithin.

[0052] The co-emulsifier includes one or more of polyether co-emulsifiers and polyol co-emulsifiers.

[0053] Polyether co-emulsifiers include PPG-26-butanol polyether-26, PPG-25-lauryl alcohol polyether-25, methyl glucetol polyether-10, cholesterol polyether-10, tridecyl alcohol polyether-12, peanut alcohol polyether-20, coconut alcohol polyether-10, PPG-25-lauryl alcohol polyether-25, methyl glucetol polyether-10, cholesterol polyether-10, tridecyl alcohol polyether-12, peanut alcohol polyether-20, or coconut alcohol polyether-10.

[0054] Polyol co-emulsifiers include ethoxydiethylene glycol, dipropylene glycol, glycerin, butylene glycol, sorbitol, isopropanol, 1,2-hexanediol, 1,2-pentanediol, or 1,3-propanediol.

[0055] In one specific embodiment, the nanocarrier comprises polyglycerol-10 oleate, lecithin, and 1,3-propanediol.

[0056] In one specific embodiment, the nanocarrier comprises polyglycerol-6 polyricinoleate, lecithin, and 1,3-propanediol.

[0057] In one specific embodiment, the nanocarrier comprises polyglycerol-10 oleate and 1,3-propanediol.

[0058] In one specific embodiment, the nanocarrier comprises polyglycerol-10 diisostearate, lecithin, and 1,3-propanediol.

[0059] In one specific embodiment, the nanocarrier comprises polyglycerol-10 oleate, lecithin, and PPG-26-butanol polyether-26.

[0060] In one specific embodiment, the particle size of the nanocarrier is 10 nm-500 nm, for example, it can be 10 nm, 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, 200 nm, 210 nm, 220 nm, 230 nm, 240 nm, 250 nm, 260 nm, 270 nm, 280 nm, 290 nm, 300 nm, 310 nm, 320 nm, 330 nm, 340 nm, 350 nm, 360 nm, 370 nm, 380 nm, 390 nm, 400 nm, 410 nm, 420 nm, 430 nm, 440 nm, 450 nm, 460 nm, 470 nm, etc. nm, 480 nm, 490 nm, 500 nm.

[0061] The particle size of the nanocarrier can be detected by methods known in the art, such as by a nanopotential particle size analyzer.

[0062] In one specific embodiment, the emulsifier content is 1%-40% based on the total mass of the skin barrier repair composition, for example, it can be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%. %, 38%, 39%, 40%; the content of the co-emulsifier is 1%-40%, for example, it can be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%.

[0063] In one specific implementation, the nanocarrier can be applied alone or further added to other formulations.

[0064] In one specific embodiment, the above-described skin barrier repair composition may further include cosmetically acceptable excipients and other active ingredients. The excipients include solvents, preservatives, oils, fragrances, etc., the solvents include water, monohydric alcohols, polyhydric alcohols, dimethyl sulfoxide, etc., and the oils include caprylic / capric triglycerides, jojoba oil, etc. The active ingredients may be, for example, water-soluble and / or oil-soluble active ingredients.

[0065] In one specific embodiment, the water-soluble active ingredients include trehalose, allantoin, betaine, β-glucan, squalene, purslane extract, pyrrolidone carboxylic acid, acetyl tetrapeptide-15, acetyl dipeptide-1 acetyl ester, etc.

[0066] In one specific embodiment, the oil-soluble active ingredient includes squalene, acetyl hexapeptide-49, etc.

[0067] This application provides a method for preparing a skin barrier repair composition. This application is not limited to any particular method; any method commonly used in the art for preparing skin barrier repair compositions is acceptable, for example, including the following steps: Intercellular lipid supplements and stratum corneum repair agents are mixed in a solvent and ultrasonically dispersed to obtain a skin barrier repair composition.

[0068] In one specific implementation, the mixing step may also include a barrier function protectant.

[0069] In one specific implementation, the mixing step may also include the addition of excipients.

[0070] In one specific embodiment, the ultrasonic dispersion is performed under heating. The heating temperature can be 60-70°C.

[0071] This application also provides a method for preparing a skin barrier repair composition. This application is not limited to any particular method; any method commonly used in the art for preparing skin barrier repair compositions is acceptable, for example, including the following steps: The oil-soluble active ingredient is mixed with an emulsifier and a co-emulsifier to obtain the oil phase; The water-soluble active ingredient is mixed with water to obtain an aqueous phase; The oil phase and the aqueous phase are mixed and then micronized to obtain a micron-sized dispersion. The above micron-sized dispersion was nano-sized to obtain a skin barrier repair composition.

[0072] The oil-soluble active ingredients include intercellular lipid supplements, and the water-soluble ingredients include stratum corneum repair agents and / or barrier function protectants.

[0073] In one specific embodiment, the oil phase mixing, water phase mixing, and / or oil phase and water phase mixing are carried out under heating. The heating temperature can be 60-70°C.

[0074] In one specific implementation, mixing the oil phase and the water phase involves adding the water phase to the oil phase.

[0075] In one specific embodiment, the micronization process is shear mixing, wherein the shear mixing speed is 4000~30000 rpm and the time is 1~20 min.

[0076] In one specific embodiment, the nano-sizing process is a high-pressure homogenization process. Preferably, the high-pressure homogenization process is carried out at a pressure of 300~1600 bar, a temperature of 20~70°C, and 1~10 cycles.

[0077] In one specific embodiment, the nano-sizing process is a high-pressure microjets treatment. Preferably, the high-pressure microjets treatment is performed at a pressure of 3000~16000 psi, a temperature of 20~70°C, and 1~10 cycles.

[0078] This application also provides the use of any of the above-described skin barrier repair compositions in the preparation of cosmetics.

[0079] Example Example 1 Based on the total mass of the composition, 1% phytosphingosine, 0.5% cholesterol, 1% sodium hyaluronate (1500kDa), 3% hydrolyzed sodium hyaluronate (10kDa), 1% tripeptide-1, and 6% dimethyl sulfoxide were added to 87.5% purified water and ultrasonically dispersed at 65°C to obtain the composition.

[0080] Example 2 Based on the total mass of the composition, 1.5% phytosphingosine, 1% sodium hyaluronate (1500kDa), 4% hydrolyzed sodium hyaluronate (10kDa), and 6% dimethyl sulfoxide were added to 87.5% purified water and ultrasonically dispersed at 65°C to obtain the composition.

[0081] Example 3 Based on the total mass of the composition, 1% phytosphingosine, 0.5% cholesterol, 3% hydrolyzed sodium hyaluronate, 1% tripeptide-1, and 6% dimethyl sulfoxide were added to 88.5% purified water and ultrasonically dispersed at 65°C to obtain a free skin barrier repair composition.

[0082] Example 4 Based on the total mass of the composition, 1% phytosphoprotein, 4% polyglycerol-10 oleate, 4% lecithin, 0.5% cholesterol, and 15% 1,3-propanediol were dissolved in a water bath at 65°C to obtain the oil phase; 1% sodium hyaluronate (1500kDa), 3% hydrolyzed sodium hyaluronate (10kDa), and 1% tripeptide-1 were added to 70.5% purified water and dissolved by heating in a water bath at 65°C to obtain the aqueous phase. The aqueous phase was added to the oil phase at a rate of 6 drops / second and stirred continuously at 65°C and 400 rpm. After being mixed evenly, the mixture was subjected to high-speed shearing at 16000 rpm for 5 min to obtain a micron-sized dispersion. The micron-sized dispersion was subjected to high-pressure homogenization at a temperature of 65°C and a pressure of 400 bar, repeated twice, and then cooled to room temperature to obtain the composition.

[0083] Example 5 The difference between Example 5 and Example 4 is that the lipid supplement is phytosphingosine and the stratum corneum repair agent is hydrolyzed sodium hyaluronate.

[0084] Examples 6-7 The only difference between Examples 6-7 and Example 5 is the content of phytosphingosine. In Example 6, the content of phytosphingosine is 5%, while in Example 7, the content of phytosphingosine is 10%.

[0085] Examples 8-9 The only difference between Examples 8-9 and Example 5 is the content of hydrolyzed sodium hyaluronate. In Example 8, the content of hydrolyzed sodium hyaluronate is 0.1%, while in Example 9, the content is 10%.

[0086] Examples 10-12 The only difference between Examples 10-12 and Example 5 is the content of sodium hyaluronate. In Example 10, the content of sodium hyaluronate is 0.5%, in Example 11 it is 5%, and in Example 12 it is 10%.

[0087] Example 13 The difference between Example 13 and Example 5 lies in the content of sodium hyaluronate, phytosphingosine, and hydrolyzed sodium hyaluronate. In Example 13, the content of sodium hyaluronate is 0.5%, phytosphingosine is 10%, and hydrolyzed sodium hyaluronate is 0.1%.

[0088] Example 14 The difference between Example 14 and Example 5 is that the lipid supplement is cholesterol and the stratum corneum repair agent is tripeptide-1.

[0089] Example 15 The difference between Example 15 and Example 5 is that the lipid supplement is ceramide.

[0090] Examples 16-18 The only difference between Examples 16-18 and Example 5 is the type of emulsifier. Example 16 uses polyglycerol-6 polyricinoleate and lecithin, Example 17 uses polyglycerol-10 diisostearate and lecithin, and Example 18 uses polyglycerol-10 oleate.

[0091] Example 19 The only difference between Example 19 and Example 5 is the type of co-emulsifier used; Example 19 uses PPG-26-butanol polyether-26.

[0092] Example 20 The difference between Example 20 and Example 4 is that the molecular weight of sodium hyaluronate used in Example 20 is 300 kDa.

[0093] Example 21 The difference between Example 21 and Example 4 is that the barrier function protectant in Example 21 is acetylated sodium hyaluronate (molecular weight of 20000 Da).

[0094] Comparative Examples 1-7 Comparative Example 1 By weight percentage, 1% phytosphingosine, 0.5% cholesterol, 1% sodium hyaluronate, and 6% dimethyl sulfoxide were added to 91.5% purified water and ultrasonically dispersed at 65°C to obtain a free skin barrier repair composition.

[0095] Comparative Example 2 By weight percentage, 1% sodium hyaluronate, 3% hydrolyzed sodium hyaluronate, 1% tripeptide-1, and 6% dimethyl sulfoxide were added to 89% purified water and ultrasonically dispersed at 65°C to obtain a free skin barrier repair composition.

[0096] Comparative Example 3 By weight percentage, 1% sodium hyaluronate and 6% dimethyl sulfoxide were added to 93% purified water and ultrasonically dispersed at 65°C to obtain a free skin barrier repair composition.

[0097] Comparative Example 4 By weight percentage, 1% phytosphingosine, 0.5% cholesterol, and 6% dimethyl sulfoxide were added to 92.5% purified water and ultrasonically dispersed at 65°C to obtain a free skin barrier repair composition.

[0098] Comparative Example 5 By weight percentage, 3% hydrolyzed sodium hyaluronate, 1% tripeptide-1, and 6% dimethyl sulfoxide were added to 90% purified water and ultrasonically dispersed at 65°C to obtain a free skin barrier repair composition.

[0099] Comparative Example 6 By weight percentage, 1.5% phytosphingosine and 6% dimethyl sulfoxide were added to 88.5% purified water and ultrasonically dispersed at 65°C to obtain a free skin barrier repair composition.

[0100] Comparative Example 7 By weight percentage, 4% hydrolyzed sodium hyaluronate and 6% dimethyl sulfoxide were added to 90% purified water and ultrasonically dispersed at 65°C to obtain a free skin barrier repair composition.

[0101] The composition of each component in the above embodiments and comparative examples is shown in Tables 1 and 2.

[0102] Table 1

[0103]

[0104]

[0105]

[0106]

[0107] Test Example 1 Stability test The compositions prepared in Examples 4-21 were placed in sealed containers and stored at room temperature and 45°C for 3 months each. Freeze-thaw experiments were conducted to check the appearance of the samples under different conditions before and after storage, and to test the particle size of the nanocompositions under different conditions before and after storage. The stability of the compositions was comprehensively evaluated.

[0108] The particle size testing method is as follows: Take an appropriate amount of the composition and dilute it 50 times with ultrapure water to make the average light intensity of the sample solution 200~300. The particle size is then measured using a Zetasizer / NanoZS90 nanopotential particle size analyzer at a 90° measurement angle and a test temperature of 25℃. Freeze-thaw test: Place the sample in a sealed container and place it at -20℃ for 48 hours, then place it at 45℃ for 48 hours. Repeat the cycle twice and observe the changes in the sample.

[0109] Meanwhile, the samples were placed at room temperature and 45°C for three months, and the changes in the samples were observed.

[0110] The results are shown in Table 3.

[0111] Table 3

[0112]

[0113] As shown in Table 3, the skin barrier repair compositions prepared in the embodiments of this application have a particle size of approximately 10-500 nm, which meets the requirements for practical applications. Taking Example 6 as an example, Figure 1 The particle size distribution curves were shown, revealing a symmetrical single-peak distribution of the nanocomposite particle size, indicating uniform particle size. The PDI value was 0.211, and the particle size was 147.8 nm. Under conditions of room temperature, 45℃ for three months, and freeze-thaw cycles, the particle size of the nanocomposite did not change significantly, and no precipitation or stratification was observed. It still meets the requirements for practical applications and exhibits good stability.

[0114] Test Example 2 Evaluation of cell proliferation promotion effect HaCaT cells in logarithmic growth phase were seeded into 96-well plates and cultured for 24 h at 37°C with 5% CO2. 100 μL of DMEM complete medium containing 83.3 µL of Examples 1-16, 20, and 21 and Comparative Examples 1-7 was added to each well of the sample groups, while the control group received only 100 μL of DMEM complete medium. After 48 h of culture, cell viability was measured using the CCK-8 assay, and absorbance (A) of each sample at 450 nm was measured using a Victor multilabel analyzer. The proliferative effects of different examples and comparative samples on HaCaT cells were compared to verify the synergistic effect of the selected active ingredients. The results are shown in Table 4.

[0115] Cell proliferation rate = (A 样品组 -A 对照组 ) / A 对照组 *100% Table 4

[0116] Validating synergistic effects using the COLBY formula Test formulas and principles E = X + Y - XY / 100 (I) or E=X+Y+Z-(XY+XZ+YZ) / 100+XYZ / 10000 (Ⅱ) X, Y, and Z represent the cell proliferation rates after cells were treated with a single component individually, respectively. E represents the theoretical cell proliferation rate after cell treatment with the composition. E 实际 The actual cell proliferation rate after cell treatment with the composition. E 实际 >E represents increased efficiency; E 实际 <E represents antagonism; E 实际 =E represents the summation.

[0117] The results are shown in Table 5 below.

[0118] Table 5

[0119] As shown in Tables 4-5, compared with the blank control, the above-mentioned examples and comparative samples all promoted HaCaT cell proliferation. Compared with the cells cultured in Comparative Examples 1-7, the cell proliferation rate in the culture medium of the skin barrier repair compositions prepared in Examples 1, 2, and 3 was significantly higher, demonstrating that two or three of the three active ingredients—barrier function protectant, lipid supplement, and stratum corneum repair agent—exhibit synergistic effects and have good barrier repair function. Furthermore, the cell proliferation rate cultured in Examples 4-21 was significantly greater than that in Examples 1 and 2, indicating that the cell proliferation-promoting effect of the skin barrier repair compositions prepared by nanodelivery technology is further superior to that of the same dose of free material.

[0120] Test Example 3 1. Preparation of compound essence (1) Preparation of blank essence Dissolve 2.0% glycerol, 0.3% carbomer, 0.1% xanthan gum, 0.5% phenoxyethanol, and 97.2% purified water at room temperature to obtain a blank serum solution.

[0121] (2) Preparation of Rhodamine B nanocarriers The oil phase was obtained by dissolving 4% polyglycerol-10 oleate, 4% lecithin, 0.5% cholesterol, and 15% 1,3-propanediol in a water bath at 65°C by weight percentage. 10% Rhodamine B was added to 66.5% purified water and dissolved by heating in a water bath at 65°C to obtain the aqueous phase; The aqueous phase was added to the oil phase at a rate of 6 drops / second and stirred continuously at 65°C and 400 rpm. After being mixed evenly, the mixture was subjected to high-speed shearing at 16000 rpm for 5 min to obtain a micron-sized dispersion. The micron-sized dispersion was subjected to high-pressure homogenization at 65°C and 400 bar for two cycles, and then cooled to room temperature to obtain Rhodamine B nanocarriers with a particle size of 140 nm.

[0122] (3) Preparation of compound essence Free Rhodamine B and Rhodamine B nanocarrier were added to the blank essence at ratios of 0.3% and 3%, respectively, to obtain free Rhodamine B compound essence and Rhodamine B nanocarrier compound essence.

[0123] 2. Transdermal test Transdermal experiments were conducted on isolated porcine skin using the vertical Franz diffusion cell method. The prepared free Rhodamine B compound essence and Rhodamine B nanocarrier compound essence were placed in the supply chamber. PBS was used as the receiving solution, and diffusion was carried out with stirring at 37°C. After 2 h and 4 h, residual samples were gently wiped off the skin, and the skin from the target area was removed, thoroughly cleaned, and dried. The samples were frozen into sections, and the sections were observed using a laser confocal microscope. The results are as follows: Figure 2 .

[0124] Figure 2 The results showed that the penetration depth of the fluorescent marker increased over time. Within the same timeframe, the fluorescence intensity of the Rhodamine B (RhoB) nanocarrier in the skin was significantly stronger than that of free Rhodamine B (RhoB), indicating that the Rhodamine B (RhoB) nanocomposition could penetrate deep into the skin tissue. This demonstrates that the nanocarrier used in this application can effectively promote the rapid penetration of the encapsulated components into the skin.

[0125] Test Example 4 1. Preparation of human efficacy test samples Dissolve 2.0% glycerol, 0.3% carbomer, 0.1% xanthan gum, 0.5% phenoxyethanol, and 97.2% purified water at room temperature to obtain a blank serum solution. Prepare test samples for each group according to Table 6 below.

[0126] Table 6

[0127] 2. Human efficacy test Thirty volunteers were selected, and a barrier damage model was created on the front of their arms by tearing off tape. Selected areas were divided at the damaged site, and control group, sample group I, and sample group II were applied respectively. The stratum corneum moisture content and transepidermal water loss were tested before the application of the sample, 2, 4, and 6 hours after the application of the sample, and 7 and 14 days later, to compare the barrier repair effect of the samples.

[0128] All tests were conducted in a constant temperature and humidity room, with a temperature of 22±1℃ and a humidity of 50±5%. Before the test, participants were required to sit quietly in the constant temperature and humidity room for 30 minutes.

[0129] The results are shown in Table 7.

[0130] Table 7

[0131] As can be seen from the data in Table 7, for skin barrier damage caused by the tape tearing test, compared with the control group, both sample group I and sample group II can increase the stratum corneum water content and reduce transepidermal water loss in both short-term and long-term tests, indicating that the active ingredients selected in this application help repair the skin barrier. Compared with sample group I, sample group II can more significantly increase the stratum corneum water content and reduce transepidermal water loss, proving that the active ingredients can more effectively exert the barrier repair function after being made into nanocarriers.

Claims

1. A skin barrier repair composition, characterized in that, The skin barrier repair composition includes an intercellular lipid supplement, a stratum corneum repair agent, and a barrier function protectant; The intercellular lipid supplement includes phytosphingosine, or a combination of phytosphingosine and cholesterol; the stratum corneum repair agent includes one or two of hydrolyzed hyaluronic acid or its salt, and tripeptide-1; the barrier function protectant includes one or two of hyaluronic acid or its salt, and acetylated hyaluronic acid or its salt. Based on the total mass of the skin barrier repair composition, the content of the intercellular lipid supplement is 0.1%-7%, the content of the stratum corneum repair agent is 0.5%-7%, and the content of the barrier function protectant is 1%-7%. The composition further includes emulsifiers and emulsifiers; The emulsifier includes one or more of polyglycerol-10 diisostearate, polyglycerol-10 oleate, and polyglycerol-10 myristate.

2. The composition according to claim 1, characterized in that, The hydrolyzed hyaluronic acid or its salt has a molecular weight of less than 10 kDa.

3. The composition according to claim 2, characterized in that, The molecular weight of the hydrolyzed hyaluronic acid or its salt is 1 kDa-10 kDa.

4. The composition according to claim 1, characterized in that, The hyaluronic acid or its salt has a molecular weight of 100 kDa or higher.

5. The composition according to claim 4, characterized in that, The molecular weight of the hyaluronic acid or its salt is 100 kDa-2000 kDa.

6. The composition according to claim 1, characterized in that, The molecular weight of the acetylated hyaluronic acid or its salt is 10 kDa-100 kDa.

7. The composition according to claim 1, characterized in that, The content of the intercellular lipid supplement is 1%-5% based on the total mass of the skin barrier repair composition; Preferably, the content of the stratum corneum repair agent is 1%-5%; Preferably, the content of the barrier function protective agent is 1%-5%.

8. The composition according to claim 1, characterized in that, The emulsifier content is 1%-40% and the co-emulsifier content is 1%-40% based on the total mass of the skin barrier repair composition. Preferably, the emulsifier includes one or two of polyether-based emulsifiers and polyol-based emulsifiers.

9. Use of the skin barrier repair composition according to any one of claims 1-8 in the preparation of cosmetics.

10. Use of the composition of any one of claims 1-8 in repairing the skin barrier.

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