Composition for maintaining skin homeostasis and application thereof

Abstract

The invention provides a composition for maintaining skin steady state and application thereof, the composition comprises hyaluronic acid oligosaccharide or salt thereof and low-molecular-weight hyaluronic acid or salt thereof, the molecular weight of the hyaluronic acid oligosaccharide or salt thereof is 800 Da to 3000 Da, and the molecular weight of the low-molecular-weight hyaluronic acid or salt thereof is 10 kDa to 500 kDa. The composition can remarkably promote keratinocytes and dermal fibroblasts to generate endogenous hyaluronic acid, thicken epidermis and cuticle and improve the moisture content in the skin cuticle, so that the homeostasis in the skin can be maintained.

Description

[0001] This case is a divisional application of the application filed on March 7, 2023, entitled "Composition for Maintaining Skin Homeostasis and Its Use Thereof", with application number 202310230675.4. Technical Field

[0002] This application belongs to the field of cosmetic technology, and specifically relates to a composition for maintaining skin homeostasis and its use. Background Technology

[0003] The skin is a natural barrier between the body and its environment. By maintaining an effective epidermal barrier, it protects the body from environmental influences, not only resisting external factors but also preventing water loss. Homeostasis, the mechanism by which organisms control their internal environment to maintain relative stability, is a more advanced mechanism developed during evolution, reducing an organism's dependence on external conditions to varying degrees. Healthy skin features a thicker epidermis and stratum corneum, as well as a firm dermis. One of the main characteristics of young, healthy skin is its strong water-retention capacity, which declines significantly with age. The key molecule for maintaining skin hydration is hyaluronic acid (HA).

[0004] The biological understanding of hyaluronic acid (HA) has evolved from that of a traditional space filler to a structural molecule that plays a crucial role in processes such as lubrication and hydration, and serves as a support for connective tissue. In vivo, most HA exists as salts, reaching high concentrations in connective tissues such as the skin, synovial fluid, and vitreous humor. Adult skin accounts for approximately 50% of total body HA. Most skin HA is located in the dermis, reaching a concentration of 0.5 mg / kg; while epidermal HA is estimated at approximately 0.1 mg / kg. Due to its rheological properties, skin HA regulates overall skin quality, hydration, permeability, and immune barrier function. Furthermore, its unique viscoelastic properties protect skin cells from mechanical damage, improve cell survival (response to injury and wound healing), and promote proliferation, migration, signal transduction, and immune surveillance. Therefore, endogenous HA is one of the essential substances for maintaining skin health and homeostasis. Summary of the Invention

[0005] The purpose of this application is to find a HA composition that can improve the overall condition of the skin by promoting the production of endogenous HA, which is of great significance for the application of hyaluronic acid in maintaining skin homeostasis. To achieve this purpose, the inventors of this application, after in-depth research, discovered that the combined use of hyaluronic acid oligosaccharides or their salts with a molecular weight of 800 Da-6000 Da and low molecular weight hyaluronic acid or its salts with a molecular weight of 10 kDa-500 kDa can effectively promote the production of endogenous hyaluronic acid, thicken the epidermis and dermis, increase the moisture content in the stratum corneum, and enhance the skin barrier function, showing a synergistic effect in maintaining skin homeostasis, thus completing this invention.

[0006] Specifically, this application relates to the following aspects:

[0007] 1. A composition for maintaining skin homeostasis, the composition comprising hyaluronic acid oligosaccharide or a salt thereof, and low molecular weight hyaluronic acid or a salt thereof, wherein the hyaluronic acid oligosaccharide or salt thereof has a molecular weight of 800 Da-3000 Da, and the low molecular weight hyaluronic acid or salt thereof has a molecular weight of 10 kDa-500 kDa.

[0008] 2. The composition according to claim 1, wherein the molecular weight of the hyaluronic acid oligosaccharide or its salt is 800 Da-2000 Da, preferably 800 Da-1000 Da.

[0009] 3. The composition according to item 1 or 2, wherein the low molecular weight hyaluronic acid or its salt has a molecular weight of 10kDa-300kDa, preferably 10kDa-100kDa.

[0010] 4. The composition according to any one of items 1-3, wherein the mass ratio of the low molecular weight hyaluronic acid or its salt to the hyaluronic acid oligosaccharide or its salt is 1:16-16:1, preferably 1:11-11:1.

[0011] 5. The composition according to any one of items 1-4, wherein the total content of the low molecular weight hyaluronic acid or its salt and the hyaluronic acid oligosaccharide or its salt is 0.0001 wt%-10 wt%, preferably 0.0005 wt%-5 wt%.

[0012] 6. The composition according to any one of items 1-5, and its use in the preparation of cosmetics.

[0013] 7. Use of the composition of any one of items 1-5 in the preparation of articles for maintaining skin homeostasis or for the preparation of articles for enhancing the skin barrier.

[0014] 8. Use of hyaluronic acid oligosaccharides or salts thereof and low molecular weight hyaluronic acid or salts thereof in the preparation of articles for maintaining skin homeostasis or for enhancing the skin barrier, wherein the molecular weight of the hyaluronic acid oligosaccharides or salts thereof is 800 Da-3000 Da, and the molecular weight of the low molecular weight hyaluronic acid or salts thereof is 10 kDa-500 kDa.

[0015] 9. The use according to item 8, wherein the mass ratio of the low molecular weight hyaluronic acid or its salt to the hyaluronic acid oligosaccharide or its salt is 1:16-16:1, preferably 1:11-11:1.

[0016] 10. The use according to item 7 or 8, wherein maintaining skin homeostasis includes one or more of thickening the epidermis, thickening the dermis, promoting the production of endogenous hyaluronic acid in the skin, and increasing the moisture content in the stratum corneum of the skin.

[0017] The composition of this application can effectively promote the production of endogenous hyaluronic acid by keratinocytes and dermal fibroblasts, thicken the epidermis and stratum corneum, significantly increase the moisture content in the stratum corneum, and enhance the skin barrier function, thereby achieving the effect of maintaining skin homeostasis. Attached Figure Description

[0018] Figure 1 The structure of a 3D full-thickness skin model is shown after using samples from the control group or each embodiment.

[0019] Figure 2 The results show the expression of endogenous hyaluronic acid in a 3D full-thickness skin model after using the control group or the sample from Example 3. Detailed Implementation

[0020] 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.

[0021] 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.

[0022] This application provides a composition for maintaining skin homeostasis, wherein the composition comprises hyaluronic acid oligosaccharide or a salt thereof, and low molecular weight hyaluronic acid or a salt thereof, wherein the molecular weight of the hyaluronic acid oligosaccharide or the salt thereof is 800 Da-3000 Da, and the molecular weight of the low molecular weight hyaluronic acid or the salt thereof is 10 kDa-500 kDa.

[0023] The molecular weight of the hyaluronic acid oligosaccharide or its salt may be, for example, 800 Da, 810 Da, 820 Da, 830 Da, 840 Da, 850 Da, 860 Da, 870 Da, 880 Da, 890 Da, 900 Da, 910 Da, 920 Da, 930 Da, 940 Da, 950 Da, 960 Da, 970 Da, 980 Da, 990 Da, 1000 Da, or 1... 100Da, 1200Da, 1300Da, 1400Da, 1500Da, 1600Da, 1700Da, 1800Da, 1900Da, 2000Da, 2100Da, 2200Da, 2300Da, 2400Da, 2500Da, 2600Da, 2700Da, 2800Da, 2900Da, 3000Da, or any value between these values.

[0024] The low molecular weight hyaluronic acid or its salt has a molecular weight of 10kDa-500kDa, for example, it can be 10kDa, 15kDa, 20kDa, 25kDa, 30kDa, 35kDa, 40kDa, 45kDa, 50kDa, 55kDa, 60kDa, 65kDa, 70kDa, 75kDa, 80kDa, 85kDa, 90kDa, 95kDa, 100kDa, 110kDa, 120kDa, 130kDa, 140kDa, 150kDa, 160kDa, 170kDa, 180kDa, 190kDa, 200kDa, 2 10kDa, 220kDa, 230kDa, 240kDa, 250kDa, 260kDa, 270kDa, 280kDa, 290kDa, 300kDa, 310kDa, 320kDa, 330kDa, 340kDa, 350kDa, 360kDa, 370kDa, 380kDa, 390kDa, 400kDa, 410kDa, 420kDa, 430kDa, 440kDa, 450kDa, 460kDa, 470kDa, 480kDa, 490kDa, 500kDa, or any value between these values.

[0025] In this application, hyaluronic acid oligosaccharides include, but are not limited to, one or a mixture of two or more of hyaluronic acid disaccharides, hyaluronic acid tetrasaccharides, hyaluronic acid hexasaccharides, hyaluronic acid octasaccharides, hyaluronic acid decasaccharides, and hyaluronic acid dodecasaccharides.

[0026] In one specific implementation, hyaluronic acid oligosaccharides are a mixture of various oligosaccharides, with hyaluronic acid tetrasaccharide as the main component.

[0027] In one specific embodiment, the molecular weight of the hyaluronic acid oligosaccharide or its salt is 800 Da-2000 Da.

[0028] In one specific embodiment, the molecular weight of the hyaluronic acid oligosaccharide or its salt is 800 Da-1000 Da.

[0029] In one specific embodiment, the low molecular weight hyaluronic acid or its salt has a molecular weight of 10kDa-300kDa.

[0030] In one specific embodiment, the low molecular weight hyaluronic acid or its salt has a molecular weight of 10kDa-100kDa.

[0031] In one specific embodiment, the low molecular weight hyaluronic acid or its salt has a molecular weight of 10kDa-50kDa.

[0032] In one specific embodiment, the mass ratio of the low molecular weight hyaluronic acid or its salt to the hyaluronic acid oligosaccharide or its salt is 1:16-16:1, for example, it can be 1:16, 1:15, 1:14, 1:13, 1:12, 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, or any value between these values.

[0033] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The molecular weight of the hyaluronic acid oligosaccharides or salts thereof is 800 Da-3000 Da, the molecular weight of the low molecular weight hyaluronic acid or salts thereof is 10 kDa-500 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:16-16:1.

[0034] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The molecular weight of the hyaluronic acid oligosaccharides or salts thereof is 800 Da-2000 Da, the molecular weight of the low molecular weight hyaluronic acid or salts thereof is 10 kDa-100 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:11-11:1.

[0035] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The hyaluronic acid oligosaccharides or salts thereof have a molecular weight of 800 Da-1000 Da, the low molecular weight hyaluronic acid or salts thereof have a molecular weight of 10 kDa-50 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:11-11:1.

[0036] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The hyaluronic acid oligosaccharides or salts thereof have a molecular weight of 800 Da, the low molecular weight hyaluronic acid or salts thereof have a molecular weight of 30 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:11 to 11:1.

[0037] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The hyaluronic acid oligosaccharides or salts thereof have a molecular weight of 800 Da, the low molecular weight hyaluronic acid or salts thereof have a molecular weight of 30 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:1.

[0038] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The hyaluronic acid oligosaccharides or salts thereof have a molecular weight of 800 Da, the low molecular weight hyaluronic acid or salts thereof have a molecular weight of 30 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:2.

[0039] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The hyaluronic acid oligosaccharides or salts thereof have a molecular weight of 800 Da, the low molecular weight hyaluronic acid or salts thereof have a molecular weight of 30 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:11.

[0040] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The hyaluronic acid oligosaccharides or salts thereof have a molecular weight of 800 Da, the low molecular weight hyaluronic acid or salts thereof have a molecular weight of 30 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:16.

[0041] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The hyaluronic acid oligosaccharides or salts thereof have a molecular weight of 800 Da, the low molecular weight hyaluronic acid or salts thereof have a molecular weight of 30 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 2:1.

[0042] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The hyaluronic acid oligosaccharides or salts thereof have a molecular weight of 800 Da, the low molecular weight hyaluronic acid or salts thereof have a molecular weight of 30 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 16:1.

[0043] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The hyaluronic acid oligosaccharides or salts thereof have a molecular weight of 800 Da, the low molecular weight hyaluronic acid or salts thereof have a molecular weight of 30 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 11:1.

[0044] The composition for maintaining skin homeostasis in this application may contain only hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof, and may further contain other ingredients.

[0045] In one specific embodiment, the total content of the low molecular weight hyaluronic acid or its salt and the hyaluronic acid oligosaccharide or its salt in the composition is 0.0001wt%-10wt%, for example, it can be 0.0001wt%, 0.0005wt%, 0.001wt%, 0.005wt%, 0.01wt%, 0.05wt%, 0.1wt%, 0.5wt%, 2wt%, 3wt%, 4wt%, 5wt%, 6wt%, 7wt%, 8wt%, 9wt%, 10wt%, or any value between these values.

[0046] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The molecular weight of the hyaluronic acid oligosaccharides or salts thereof is 800 Da-3000 Da, and the molecular weight of the low molecular weight hyaluronic acid or salts thereof is 10 kDa-500 kDa. The mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:16-16:1. In the composition, the total content of the low molecular weight hyaluronic acid or salts thereof and the hyaluronic acid oligosaccharides or salts thereof is 0.0001 wt%-10 wt%.

[0047] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The molecular weight of the hyaluronic acid oligosaccharides or salts thereof is 800 Da-2000 Da, and the molecular weight of the low molecular weight hyaluronic acid or salts thereof is 10 kDa-100 kDa. The mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:11-11:1. In the composition, the total content of the low molecular weight hyaluronic acid or salts thereof and the hyaluronic acid oligosaccharides or salts thereof is 0.0001 wt%-10 wt%.

[0048] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The molecular weight of the hyaluronic acid oligosaccharides or salts thereof is 800 Da-1000 Da, and the molecular weight of the low molecular weight hyaluronic acid or salts thereof is 10 kDa-50 kDa. The mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:11-11:1. In the composition, the total content of the low molecular weight hyaluronic acid or salts thereof and the hyaluronic acid oligosaccharides or salts thereof is 0.0001 wt%-10 wt%.

[0049] In one specific embodiment, the composition for maintaining skin homeostasis consists of hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof.

[0050] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The molecular weight of the hyaluronic acid oligosaccharides or salts thereof is 800 Da-3000 Da, and the molecular weight of the low molecular weight hyaluronic acid or salts thereof is 10 kDa-500 kDa.

[0051] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The molecular weight of the hyaluronic acid oligosaccharides or salts thereof is 800 Da-2000 Da, the molecular weight of the low molecular weight hyaluronic acid or salts thereof is 10 kDa-500 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:16-16:1.

[0052] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The molecular weight of the hyaluronic acid oligosaccharides or salts thereof is 800 Da-1000 Da, the molecular weight of the low molecular weight hyaluronic acid or salts thereof is 10 kDa-100 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:11-11:1.

[0053] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The molecular weight of the hyaluronic acid oligosaccharides or salts thereof is 800 Da-1000 Da, the molecular weight of the low molecular weight hyaluronic acid or salts thereof is 10 kDa-50 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:11-11:1.

[0054] In one specific embodiment, the composition for maintaining skin homeostasis comprises hyaluronic acid oligosaccharides or salts thereof, and low molecular weight hyaluronic acid or salts thereof. The hyaluronic acid oligosaccharides or salts thereof have a molecular weight of 800 Da, the low molecular weight hyaluronic acid or salts thereof have a molecular weight of 30 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salts thereof to the hyaluronic acid oligosaccharides or salts thereof is 1:11-11:1.

[0055] This application also provides the use of any of the above-described compositions for maintaining skin homeostasis in the preparation of cosmetics.

[0056] This application also provides the use of hyaluronic acid oligosaccharides or salts thereof and low molecular weight hyaluronic acid or salts thereof in maintaining skin homeostasis, or the use of any of the above-mentioned compositions for maintaining skin homeostasis in the preparation of articles for maintaining skin homeostasis.

[0057] This application also provides the use of hyaluronic acid oligosaccharides or salts thereof and low molecular weight hyaluronic acid or salts thereof in enhancing the skin barrier, or the use of any of the above-mentioned compositions for maintaining skin homeostasis in the preparation of articles for enhancing the skin barrier.

[0058] The hyaluronic acid oligosaccharide or its salt has a molecular weight of 800 Da-3000 Da, and the low molecular weight hyaluronic acid or its salt has a molecular weight of 10 kDa-500 kDa. Furthermore, the mass ratio between the two can be as described above.

[0059] Maintaining skin homeostasis can include one or more of the following: thickening the epidermis, thickening the dermis, promoting the production of endogenous hyaluronic acid in the skin, or increasing the moisture content in the stratum corneum.

[0060] Example

[0061] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0062] Unless otherwise specified, all materials and reagents used in the following examples are commercially available. The hyaluronic acid oligosaccharides and low molecular weight sodium hyaluronate used were purchased from Bloomage Biotechnology Co., Ltd.

[0063] Example 1

[0064] Weigh out 30 kDa low molecular weight sodium hyaluronate (trade name: Hybloom). TM 50g of low molecular weight sodium hyaluronate and 50g of hyaluronic acid oligosaccharide with a molecular weight of 800 Da (trade name: Weizhen HA4) are mixed to obtain a hyaluronic acid composition.

[0065] Example 2

[0066] Weigh out 30 kDa low molecular weight sodium hyaluronate (trade name: Hybloom). TM 34g of low molecular weight sodium hyaluronate and 66g of hyaluronic acid oligosaccharide with a molecular weight of 800 Da (trade name: Weizhen HA4) were mixed to obtain a hyaluronic acid composition.

[0067] Example 3

[0068] Weigh out 30 kDa low molecular weight sodium hyaluronate (trade name: Hybloom). TM 9g of low molecular weight sodium hyaluronate and 91g of hyaluronic acid oligosaccharide with a molecular weight of 800 Da (trade name: Weizhen HA4) were mixed to obtain a hyaluronic acid composition.

[0069] Example 4

[0070] Weigh out 30 kDa low molecular weight sodium hyaluronate (trade name: Hybloom). TM 91g of low molecular weight sodium hyaluronate and 9g of hyaluronic acid oligosaccharide with a molecular weight of 800 Da (trade name: Weizhen HA4) were mixed to obtain a hyaluronic acid composition.

[0071] Example 5

[0072] Weigh 6g of low molecular weight sodium hyaluronate with a molecular weight of 30kDa (trade name: HybloomTM low molecular weight sodium hyaluronate) and 94g of hyaluronic acid oligosaccharide with a molecular weight of 800Da (trade name: MicroTrue HA4), and mix them to obtain a hyaluronic acid composition.

[0073] Comparative Example 1

[0074] Weigh out 30 kDa low molecular weight sodium hyaluronate (trade name: Hybloom). TM 100g of low molecular weight sodium hyaluronate.

[0075] Comparative Example 2

[0076] Weigh out 100g of hyaluronic acid oligosaccharide (trade name: Weizhen HA4) with a molecular weight of 800 Da.

[0077] Comparative Example 3

[0078] Weigh 50g of high molecular weight sodium hyaluronate with a molecular weight of 100wDa (trade name: HybloomTM high molecular weight sodium hyaluronate) and 50g of hyaluronic acid oligosaccharide with a molecular weight of 800Da (trade name: MicroTrue HA4), and mix them to obtain a hyaluronic acid composition.

[0079] Comparative Example 4

[0080] Weigh out 50g of low molecular weight sodium hyaluronate with a molecular weight of 30kDa (trade name: HybloomTM low molecular weight sodium hyaluronate) and 50g of sodium hyaluronate with a molecular weight of 7000Da (trade name: oligomeric sodium hyaluronate), and mix them to obtain a hyaluronic acid composition.

[0081] The specific amounts of hyaluronic acid oligosaccharides and low molecular weight sodium hyaluronate used in the above embodiments and comparative examples are shown in Table 1.

[0082] Table 1

[0083]

[0084]

[0085] Experimental Example 1

[0086] A 3D full-thickness skin model is a living tissue reconstructed in vitro from normal human skin cells using tissue engineering techniques and appropriate culture media. This tissue, similar in structure to human skin, can be used for screening active ingredients. By investigating the effects of active ingredients on the tissue structure of the skin model, beneficial active ingredients for the skin can be preliminarily screened.

[0087] 1. Sample preparation

[0088] The compositions prepared in Examples 1, 2, 3, 4, and 5 were dissolved in a certain amount of DMEM medium to obtain samples 1-5 with a final mass concentration of 0.1%.

[0089] 2. Construction of 3D Full-Layer Skin Model

[0090] A 3D full-thickness skin model was constructed by combining collagen with human dermal fibroblasts to form the dermis layer, and then human keratinocytes were seeded onto the dermis layer to form the epidermis layer, resulting in a complete skin model with a dermal-epidermal structure. Samples 1, 2, 3, 4, and 5 were then added and cultured at 37°C and 5% CO2 for 11 days, while the control group received no treatment.

[0091] 3. Paraffin tissue sections of a 3D full-thickness skin model

[0092] The tissues were placed in embedding casks and subjected to a gradient dehydration process using 4% paraformaldehyde, 70% ethanol-water solution, 80% ethanol-water solution, 90% ethanol-water solution, 95% ethanol-water solution, anhydrous ethanol I, anhydrous ethanol II, methylcyclohexane I, and methylcyclohexane II, with each solution lasting 1 hour. After dehydration, the tissues were embedded in paraffin wax, trimmed, and cut into 5 μm thick paraffin sections.

[0093] 4. 3D full-thickness skin model hematoxylin-eosin staining

[0094] Paraffin sections were dewaxed and rehydrated by soaking in methylcyclohexane I, methylcyclohexane II, anhydrous ethanol, 95% ethanol-water solution, 80% ethanol-water solution, 70% ethanol-water solution, and distilled water for 10 min each. After staining with hematoxylin for 8 min, they were differentiated in hydrochloric acid-ethanol solution for 2 s and then reblued in ammonia solution for 1 min. They were then stained with eosin solution for 1 min, and finally dehydrated in 70% ethanol-water solution, 95% ethanol-water solution, anhydrous ethanol, and methylcyclohexane solution, and mounted with neutral resin. The sections were then photographed under a microscope. The results are shown below. Figure 1 .

[0095] 5. Frozen tissue sections of a 3D full-thickness skin model

[0096] The 3D full-thickness skin model was placed in OCT tissue embedding medium and rapidly cooled with liquid nitrogen. The embedded tissue block was then placed in a cryostat and sliced ​​into sections with a thickness of 5 μm.

[0097] 6. Immunofluorescence staining of ice-cut tissue sections from a 3D full-thickness skin model.

[0098] Sections were fixed with ice-cold methanol at -20°C, washed three times with PBS, and then incubated with blocking buffer at room temperature for 1 hour. After incubation, the corresponding primary antibody was added, and the sections were incubated overnight at 4°C. The next day, the sections were washed three times with PBS, and then the corresponding secondary antibody was added and incubated at room temperature in the dark for 1.5 hours. Finally, the sections were stained with DAPI and mounted, and then observed and photographed under a fluorescence microscope. Results are shown below. Figure 2 .

[0099] 7. Results Display

[0100] like Figure 1 As shown, Examples 1, 2, 3, 4, and 5 all thickened the epidermis and stratum corneum of the 3D full-thickness skin model compared to the control group.

[0101] like Figure 2 As shown, fluorescence imaging reveals the expression of endogenous hyaluronic acid in a full-thickness skin model. In the control group, the fluorescently displayed area is the lighter-colored region within the white frame, while in Example 3, the fluorescently displayed area is the lighter-colored region below the white line. The figure demonstrates that Example 3 promotes the expression of endogenous HA in the 3D full-thickness skin model.

[0102] The above results demonstrate that the embodiments of this application can promote the thickening of the epidermis and stratum corneum, enhance the skin's barrier function, and promote the formation of skin homeostasis.

[0103] Experimental Example 2

[0104] 1. Sample preparation

[0105] The compositions prepared in Examples 1-5 and Comparative Examples 1-4 were dissolved in a certain amount of PBS to obtain samples with final mass concentrations of 0.001%, 0.01%, 0.1%, and 1%, respectively. The control group was a blank PBS solution.

[0106] 2. Subject requirements and study conditions

[0107] Healthy participants aged 20-60 years with no history of skin diseases or cosmetic allergies were selected on a voluntary basis. Before the test, participants were required to clean the inside of their forearms and remain stable under the test conditions for at least 30 minutes. During the test, participants were prohibited from drinking water, eating, engaging in strenuous activity, or using other products of the same type. The test environment was set at 20-22°C and 50% relative humidity (RH). All participants' cooperation was voluntary.

[0108] 3. Use of test samples by subjects

[0109] Each subject used the same gradient concentration of the test sample on both arms. Moisture content was measured on day 0 and day 14 of sample use. Statistical data were then compiled based on the different test samples used. Test site marking: Test areas (4cm × 4cm) were marked on the inner side of each subject's left and right forearms using a mold. The test sample concentration was 2.0 ± 0.1 mg / cm². 2 The dosage was applied evenly to the test area, and 8 subjects were randomly selected for each test sample.

[0110] 4. Determination of skin moisture content

[0111] The skin moisture content of the subjects was measured at marked points on the inner forearm of the subjects at 0h and 14d after using the test sample using a Corneometer CM825. The results are shown in Table 2. There were no significant differences in the baseline skin moisture content among the groups.

[0112] 5. Results show

[0113] Examples 1-5, at concentrations of 0.001%, 0.01%, 0.1%, and 1%, all increased the moisture content of the stratum corneum, promoting the maintenance of skin homeostasis. Examples 1-5 showed statistically significant differences, even extremely significant differences, compared to Comparative Examples 1 and 2, indicating that the combination of low-molecular-weight hyaluronic acid and hyaluronic acid synergistically increased the moisture content of the stratum corneum, strengthening the skin barrier. Example 3 showed the most significant effect. While Comparative Examples 1, 2, 3, and 4 also increased the moisture content of the stratum corneum, their effects were not as pronounced as those of Examples 1-5.

[0114] Table 2 Skin Moisture Content

[0115]

[0116]

[0117] Wherein, "*" indicates that P<0.05 indicates a statistically significant difference, "**" indicates that P<0.01 indicates a statistically significant difference, and "***" indicates that P<0.001 indicates an extremely statistically significant difference.

[0118] "-" indicates that no statistical analysis was performed.

Claims

1. A composition for maintaining skin homeostasis, the composition comprising hyaluronic acid oligosaccharide or a salt thereof, and low molecular weight hyaluronic acid or a salt thereof, wherein the molecular weight of the hyaluronic acid oligosaccharide or salt thereof is 800 Da-1000 Da, the molecular weight of the low molecular weight hyaluronic acid or salt thereof is 30 kDa-100 kDa, and the mass ratio of the low molecular weight hyaluronic acid or salt thereof to the hyaluronic acid oligosaccharide or salt thereof is 1:16-16:

1.

2. The composition according to claim 1, wherein the mass ratio of the low molecular weight hyaluronic acid or its salt to the hyaluronic acid oligosaccharide or its salt is 1:11-11:

1.

3. The composition according to claim 1 or 2, wherein the total content of the low molecular weight hyaluronic acid or its salt and the hyaluronic acid oligosaccharide or its salt is 0.0001 wt% to 10 wt%.

4. The composition according to claim 3, wherein the total content of the low molecular weight hyaluronic acid or its salt and the hyaluronic acid oligosaccharide or its salt is 0.0005wt%-5wt%.

5. The composition according to claim 1, and its use in the preparation of cosmetics.

6. Use of the composition of any one of claims 1-5 in the preparation of articles for maintaining skin homeostasis or for preparing articles for enhancing the skin barrier.

7. The use according to claim 6, wherein maintaining skin homeostasis includes one or more of the following: thickening the epidermis, thickening the dermis, promoting the production of endogenous hyaluronic acid in the skin, and increasing the moisture content in the stratum corneum of the skin.

8. The use of hyaluronic acid oligosaccharides or salts thereof and low molecular weight hyaluronic acid or salts thereof in the preparation of products for maintaining skin homeostasis or for enhancing the skin barrier, wherein, The molecular weight of the hyaluronic acid oligosaccharide or its salt is 800 Da-1000 Da, the molecular weight of the low molecular weight hyaluronic acid or its salt is 30 kDa-100 kDa, and the mass ratio of the low molecular weight hyaluronic acid or its salt to the hyaluronic acid oligosaccharide or its salt is 1:16-16:

1.

9. The use according to claim 8, wherein, The mass ratio of the low molecular weight hyaluronic acid or its salt to the hyaluronic acid oligosaccharide or its salt is 1:11-11:

1.

10. The use according to claim 8 or 9, wherein maintaining skin homeostasis includes one or more of thickening the epidermis, thickening the dermis, promoting the production of endogenous hyaluronic acid in the skin, and increasing the moisture content in the stratum corneum of the skin.

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