Application of hyaluronic acid or salt thereof as oxytocin generation accelerant

By using hyaluronic acid or its salt with a molecular weight between 379-5000 Da as a promoter of oxytocin production, the problem of difficult to effectively promote oxytocin production in the skin in the prior art is solved, the effect of significantly increasing the expression level of oxytocin is achieved, and the skin care application of hyaluronic acid is expanded.

CN119745730APending Publication Date: 2025-04-04BLOOMAGE BIOTECHNOLOGY CORP LTD
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Patent Information

Application Number
CN202411971672.7
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-12-30
Publication Date
2025-04-04

AI Technical Summary

Technical Problem

The prior art is difficult to effectively promote the production of oxytocin in the skin. Oxytocin plays an important role in skin health, but developing new neurobeautics ingredients to promote their production is still a research topic.

Method used

Hyaluronic acid or its salt with a molecular weight between 379-5000 Da is used as a promoter of oxytocin production, and the production and secretion of oxytocin are promoted through contact with skin cells.

Benefits of technology

It significantly increases the expression level of oxytocin in skin cells, expands the skin care effects of hyaluronic acid, and provides new development ideas for neurobeauty products and skin health products.

✦ Generated by Eureka AI based on patent content.

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Abstract

The invention relates to the field of skin care products, and discloses an application of hyaluronic acid with the molecular weight of 379-5000Da or a salt thereof as an oxytocin generation accelerant. The new skin care effect of hyaluronic acid is expanded, a new thought is provided for product formula development, and huge market application value and economic benefits are achieved.
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Description

Technical Field

[0001] The present application relates to the field of skin care products, and in particular to the application of hyaluronic acid or its salt as an oxytocin production promoter. Background Art

[0002] Neurocosmetics is an innovative product developed recently in response to research progress on skin aging. The concept of "neurocosmetics" was first proposed by Professor Misery in 2000, and then received great attention at the New York Society of Cosmetic Chemists in 2007. It is a non-toxic, bioactive topical product whose ingredients work at the neural level, that is, achieving neurocosmetics.

[0003] In order to improve the appearance and defects of the skin, current research on neurocosmetics is mainly focused on ingredients with similar structures to endogenous neurotransmitters. Neurocosmetic ingredients can exert their effects through the following mechanisms: (1) Directly acting on the endings of skin nerve fibers as regulators of neurotransmitter release. For example, botulinum toxin-like peptides can promote facial muscle relaxation to smooth wrinkles. In another example, neuron-inhibiting peptides are mainly used to reduce the reactivity of allergic skin to environmental stimuli (temperature changes, air humidity, smoke, etc.). (2) Acting as agonist / antagonist molecules of neuropeptide receptors or neurotransmitter effector modulators to regulate the function of non-neuronal cells.

[0004] Oxytocin is a peptide hormone secreted by the posterior pituitary gland and synthesized by the paraventricular nucleus and supraoptic nucleus of the hypothalamus. It is composed of 9 amino acids and is transported to the neurohypophysis for release at a rate of 2 to 3 mm per day.

[0005] In recent years, studies have found that oxytocin may also play an important role in skin physiology and pathology. Human skin cells such as keratinocytes and dermal fibroblasts can also produce oxytocin autonomously, and oxytocin receptors are also expressed on these two cells. The oxytocin system in the skin regulates the proliferation, inflammation and oxidation of skin cells (Deing V et al. (2013). Oxytocin modulates proliferation and stress responses of human skin cells: implications for atopic dermatitis. Experimental Dermatology.), and oxytocin can inhibit cell senescence induced by the aging-associated secretory phenotype (S.-Y. Cho et al. (2019). Oxytocin alleviates cellular senescence through oxytocin receptor-mediated extracellular signal-regulated kinase / Nrf2 signalling. British Journal of Dermatolog.). Oxytocin has been found to act as a TRPV1 agonist and improve pain hypersensitivity (Nersesyan Y, Demirkhanyan L, Cabezas-Bratesco D, et al. Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1[J]. Cell Reports, 2017, 21(6): 1681. DOI: 10.1016 / j.celrep.2017.10.063.). Activation of oxytocin receptors on the skin contributes to oxytocin-mediated analgesia (Grinevich, Valery et al. (2017). Oxytocin: pain relief in skin.).

[0006] Oxytocin has been shown to mediate multiple functions of skin cells, exerting positive effects on the skin, thereby promoting skin homeostasis and overall skin health.

[0007] Therefore, promoting the secretion of oxytocin in the skin plays a vital role in skin health, and the development of new neurocosmetic ingredients that can have beneficial effects on the skin remains an active research topic in this field. Summary of the invention

[0008] In order to solve the above problems, the present application found that hyaluronic acid or its salt with a molecular weight between 379-5000Da has the effect of promoting the production of oxytocin in the skin. Since oxytocin has many beneficial effects on the skin, this expands the new skin care efficacy of hyaluronic acid and provides new ideas for product formula development, which has huge market application value and economic benefits.

[0009] According to the first aspect of the present application, the use of hyaluronic acid or a salt thereof as an oxytocin production promoter is disclosed, wherein the molecular weight of the hyaluronic acid or a salt thereof is between 379-5000 Da.

[0010] On the other hand, the present application also discloses the use of hyaluronic acid or its salt in promoting skin cells to produce oxytocin, wherein the molecular weight of the hyaluronic acid or its salt is between 379-5000Da.

[0011] Preferably, the skin cells include dermal fibroblasts and keratinocytes.

[0012] Preferably, hyaluronic acid or a salt thereof is applied to the skin to produce oxytocin in skin cells.

[0013] On the other hand, the present application also discloses the use of hyaluronic acid or its salt in the preparation of a product for promoting the production of oxytocin in the skin, wherein the molecular weight of the hyaluronic acid or its salt is between 379-5000Da.

[0014] On the other hand, the present application also discloses the use of hyaluronic acid or its salt in the preparation of neurocosmetic products, wherein the molecular weight of the hyaluronic acid or its salt is between 379-5000Da.

[0015] Furthermore, the hyaluronic acid or its salt is used as an oxytocin production promoter in the preparation of neurocosmetic products.

[0016] On the other hand, the present application also discloses the use of hyaluronic acid or its salt in the preparation of a product for increasing the pain threshold of the skin, wherein the molecular weight of the hyaluronic acid or its salt is between 379-5000 Da.

[0017] Furthermore, the hyaluronic acid or its salt is used as an oxytocin production promoter in the preparation of a product for increasing the pain threshold of the skin.

[0018] On the other hand, the present application also discloses the use of hyaluronic acid or its salt in the preparation of a product for reducing and / or alleviating the sensory sensitivity of the skin, wherein the molecular weight of the hyaluronic acid or its salt is between 379-5000 Da.

[0019] Furthermore, the hyaluronic acid or its salt is used as an oxytocin production promoter in the preparation of a product for reducing and / or alleviating the sensory sensitivity of the skin.

[0020] Furthermore, the product is used to reduce and / or relieve skin pain.

[0021] Preferably, the molecular weight of the hyaluronic acid or its salt is between 700-2000 Da.

[0022] wherein the molecular weight of the hyaluronic acid or its salt may be 379Da, 380Da, 390Da, 400Da, 450Da, 500Da, 550Da, 600Da, 650Da, 700Da, 710Da, 720Da, 730Da, 740Da, 750Da, 760Da, 770Da, 780Da, 790Da, 800Da, 810Da, 820Da, 830Da, 840Da, 850Da, 860Da, 870Da, 880Da, 890Da, 900Da, 910Da, 920Da, 930Da, 940Da, 950Da, 960Da, 970Da, 980Da, 990Da, 1000Da, 1100Da, 1200Da, 1300Da, 400 Da, 4500 Da, 4600 Da, 4700 Da, 4800 Da, 4900 Da, 5000 Da, 5100 Da, 5200 Da, 5300 Da, 5400 Da, 5500 Da, 5600 Da, 5700 Da, 5800 Da, 5900 Da, 6000 Da, 6100 Da, 6200 Da, 6300 Da, 6400 Da, 6500 Da, 6600 Da, 6700 Da, 6800 Da, 6900 Da, 7000 Da, 7100 Da, 7200 Da, 7300 Da, 7400 Da, 7500 Da, 7600 Da, 7700 Da, 7800 Da, 7900 Da, 8000 Da,

[0023] Furthermore, the reducing end of the hyaluronic acid or its salt comprises a uronic acid group.

[0024] Furthermore, the cation of the hyaluronic acid or its salt is selected from at least one of H, K, Na, Ca or Zn.

[0025] Furthermore, the product is also used for at least one of repairing the skin barrier, regulating the oxidative stress response of the skin, alleviating skin inflammation and / or slowing down the aging of skin cells. More preferably, it is used for two, three or four of the above effects.

[0026] Preferably, the application is achieved by promoting the production of oxytocin and increasing the content of oxytocin through hyaluronic acid or a salt thereof.

[0027] On the other hand, the present application also provides an oxytocin production promoter, which comprises hyaluronic acid or a salt thereof, and the molecular weight of the hyaluronic acid or the salt thereof is between 379-5000Da.

[0028] On the other hand, the present application also provides a neurocosmetic product, which contains hyaluronic acid or a salt thereof, and the molecular weight of the hyaluronic acid or the salt thereof is between 379-5000Da.

[0029] The neurocosmetic product or oxytocin production promoter described in the present application may also be added with excipients, which may be appropriate solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesive agents, integrators, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculating agents, filter aids, release retardants, etc.

[0030] The neurocosmetic product or oxytocin production promoter described in the present application can be prepared by a general method, wherein one or more diluents or carriers can be added, for example, in an external application form, such as an emulsion, a suspension, and the like.

[0031] On the other hand, the present application also provides the use of the neurocosmetic product for at least two of the following effects: repairing the skin barrier, regulating the oxidative stress response of the skin, relieving skin inflammation and / or slowing down skin cell aging. More preferably, it is used for three or four of the above effects.

[0032] The amount of hyaluronic acid or its salt to be used according to the present application can vary within a wide range to determine a suitable amount, depending on the desired cosmetic effect. For example, its content in the product can be 0.001%-5%.

[0033] The beneficial effects of this application include but are not limited to:

[0034] This application pioneered the discovery that hyaluronic acid or its salts with a molecular weight between 379-5000Da have the effect of promoting the production of oxytocin in the skin, expanding the new skin care effects of hyaluronic acid and providing new ideas for product formula development. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] The drawings described herein are used to provide a further understanding of the present application and constitute a part of the present application. The illustrative embodiments of the present application and their descriptions are used to explain the present application and do not constitute an improper limitation on the present application. In the drawings:

[0036] Figure 1 It is a schematic diagram of the immunofluorescence quantitative results in the experimental example of the present invention;

[0037] Figure 2 Schematic diagram of immunofluorescence staining results in the experimental example of the present invention. DETAILED DESCRIPTION

[0038] The present application is described in detail below in conjunction with examples, but the present application is not limited to these examples. Unless otherwise specified, the raw materials and catalysts in the examples of the present application are purchased through commercial channels.

[0039] The present application provides a general and / or specific description of the materials and test methods used in the experiments. In the following examples, unless otherwise specified, % means wt%, i.e., weight percentage. The reagents or instruments used without indicating the manufacturer are all conventional reagent products that can be obtained commercially.

[0040] Experimental example Oxytocin secretion test

[0041] This test uses immunofluorescence to qualitatively and quantitatively determine the changes in oxytocin secretion levels in human dermal fibroblasts after treatment with the test substance compared with the blank control group, and evaluates whether the test substance can increase the oxytocin secretion level based on the significant difference.

[0042] 1. Cell Model and Experimental Materials

[0043]

[0044] 2. Main equipment

[0045] CO2 incubator (Thermo, 160i), biological safety cabinet (Thermo), and fluorescence inverted microscope (Leica).

[0046] 3. Experimental Methods

[0047] 3.1 Experimental Grouping

[0048]

[0049] 3.2 Experimental methods

[0050] (1) Experimental sample preparation:

[0051] Sodium hyaluronate No. 1, acetylated sodium hyaluronate, and sodium hyaluronate No. 2 were diluted with DMEM culture medium to prepare 0.1 wt % solutions for use.

[0052] (2) Methods:

[0053] The human dermal fibroblast cell line was plated in a 24-well plate with a cell slide at a density of 15,000 / well and cultured in an incubator for 24 hours. The cells were treated with the following treatment conditions.

[0054] Blank control group: the cell culture medium was aspirated and replaced with fresh culture medium, and the well plate was cultured for 72 h.

[0055] Experimental group: the cell culture medium was aspirated and replaced with a 0.1 wt % standby solution, and the well plate was cultured for a further 72 h.

[0056] Immunofluorescence test: Collect cell slides separately, fix cells with ice methanol for 15 minutes, add anti-Oxytocin antibody and incubate at 4°C overnight, discard the supernatant, add Goat-anti-Rb IgG secondary antibody and incubate at room temperature for 1.5 hours, and use DAPI mounting medium to seal the slides. Observe and take fluorescent pictures under a Leica inverted fluorescence microscope, and then use Image J software to quantify the fluorescence intensity and calculate the relative fluorescence intensity. The calculation formula is as follows:

[0057]

[0058] The fluorescence intensity of the blank control group is defined as N0 and is set to 100% as a reference for the oxytocin content under normal conditions. The fluorescence intensity of the experimental group is defined as N t GraphPad prism6 software was used to plot the data and test the significance of oxytocin expression levels among samples. *p<0.05 indicates statistically significant differences.

[0059] 4. Experimental Results

[0060] As shown in Table 1, Figure 1-2 As shown in the figure, compared with the blank control group, the expression level of oxytocin in human dermal fibroblasts was significantly increased after treatment with sodium hyaluronate No. 1, while there was no significant difference in the expression level of oxytocin in human dermal fibroblasts compared with the blank control group after treatment with acetylated sodium hyaluronate and sodium hyaluronate No. 2, which proves that sodium hyaluronate No. 1 has the effect of promoting the expression of oxytocin.

[0061] Table 1 Relative promotion rate of oxytocin

[0062]

[0063] The above is only the embodiment of the present application, and the protection scope of the present application is not limited by these specific embodiments, but is determined by the claims of the present application. For those skilled in the art, the present application can have various changes and variations. Any modification, equivalent replacement, improvement, etc. made within the technical ideas and principles of the present application should be included in the protection scope of the present application.

Claims

1. Use of hyaluronic acid or its salt as an oxytocin production promoter, characterized in that: The molecular weight of the hyaluronic acid or its salt is between 379-5000Da.

2. Use of hyaluronic acid or its salt in promoting skin cells to produce oxytocin, characterized in that: The molecular weight of the hyaluronic acid or its salt is between 379-5000Da.

3. Use of hyaluronic acid or its salt in the preparation of a product for promoting the production of oxytocin in the skin, characterized in that: The molecular weight of the hyaluronic acid or its salt is between 379-5000Da.

4. Use of hyaluronic acid or its salt in the preparation of neurobeauty products, characterized in that: The molecular weight of the hyaluronic acid or its salt is between 379-5000Da.

5. Use of hyaluronic acid or its salt in preparing a product for increasing the pain threshold of the skin, characterized in that: The molecular weight of the hyaluronic acid or its salt is between 379-5000Da.

6. Use in the preparation of a product for reducing and / or alleviating the sensory sensitivity of the skin, characterized in that The molecular weight of the hyaluronic acid or its salt is between 379-5000Da.

7. The use according to any one of claims 3 to 6, characterized in that: The product is used to reduce and / or relieve irritation of the skin.

8. The use according to claim 7, characterized in that: The product is also used to repair the skin barrier, regulate the skin's oxidative stress response, relieve skin inflammation and / or slow down skin cell aging.

9. The use according to any one of claims 1 to 8, characterized in that: The molecular weight of the hyaluronic acid or its salt is between 700-2000Da.

10. The use according to any one of claims 1 to 9, characterized in that: The cation of the hyaluronic acid or its salt is selected from at least one of H, K, Na, Ca or Zn.