A combination of high molecular weight cross-linked hyaluronic acid and low molecular weight non-cross-linked hyaluronic acid

JP2024543648A5Pending Publication Date: 2025-12-15LVMH RECH
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Patent Information

Application Number
JP2024534413
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2021-12-10
Filing Date
2022-12-08
Publication Date
2025-12-15

AI Technical Summary

Technical Problem

Existing cosmetic compositions using hyaluronic acid fillers provide a quick smoothing effect but negatively impact moisturization, and there is a need for a formulation that combines rapid smoothing with moisturizing benefits for the skin and lips.

Method used

A combination of high molecular weight cross-linked hyaluronic acid and low molecular weight non-cross-linked hyaluronic acid is used in a cosmetic composition, with specific molecular weights and crosslinking percentages to enhance moisturization and smoothing effects.

Benefits of technology

The combination provides a synergistic effect, improving moisturization and achieving a rapid smoothing and plumping effect on the skin and lips, reducing signs of aging and enhancing firmness and elasticity.

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Abstract

The present invention relates to a cosmetic composition comprising, in a physiologically acceptable medium, a combination of at least one high molecular weight cross-linked hyaluronic acid and a low molecular weight non-cross-linked hyaluronic acid, as defined in the present invention.
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Description

[Technical field]

[0001] The present invention relates to the field of cosmetics. It particularly relates to a specific combination of high molecular weight cross-linked hyaluronic acid and low molecular weight non-cross-linked hyaluronic acid, intended to provide a rapid smoothing effect and / or an increase in density and / or volume, especially on keratinous substances of the skin and / or lips. [Background technology]

[0002] Hyaluronan is one of the essential components of the extracellular matrix. In the skin, hyaluronan is synthesized by fibroblasts and secreted from them into the extracellular space. Hyaluronan is particularly involved in the organization and structure of the dermis, helping to ensure its firmness and elasticity. In this tissue, tight junctions play an important role in regulating water balance and epidermal permeability (Furuse et al., 2002. J Cell Biol. 156, 1099-1111; Morita et al., 2011. J Derm Sci. 31, 81-89). Similarly, fibrillin-1 (a 340 kDa glycoprotein) is an essential component of the elastic meshwork of the dermis. In addition, hyaluronan has a high water-retaining capacity. Thus, hyaluronan plays a crucial role in regulating skin moisturization.

[0003] For many years, it has been possible to produce hyaluronic acid industrially, in particular by bacterial fermentation, and the beauty (or cosmetics) industry commonly uses this molecule for its anti-aging (or anti-aging) and moisturizing properties.

[0004] Structurally, hyaluronic acid is a polymer formed by repeating disaccharide monomers, consisting of glucuronic acid and N-acetylglucosamine linked by alternating β-1,4 and β-1,3 glycosidic bonds. Like other polymers, hyaluronic acid is a macromolecule whose molar mass can vary from several thousand Da to several million Da (approximately 5000-20,000,000 Da), depending on the number of repeats.

[0005] It is common to add fillers to cosmetic formulations to obtain a rapid smoothing effect (which is also an anti-aging factor), obscuring the visual and tactile irregularities of the skin and reducing the signs of aging, including fine lines and wrinkles, through optical effects.However, fillers are known to have a negative impact on the moisturizing effect provided by hyaluronic acid.

[0006] Thus, there is a need to provide new moisturizing cosmetic compositions that also provide a rapid smoothing effect on the skin and / or lips.

[0007] The applicant has rigorously developed a new cosmetic composition that meets this requirement. Indeed, surprisingly, the applicant has been able to demonstrate that a specific combination of at least one high molecular weight cross-linked hyaluronic acid and at least one low molecular weight non-cross-linked hyaluronic acid can significantly (or notably) increase the moisturizing and rapid smoothing effect on keratinous materials. The applicant has also been able to show that this combination can provide a smoothing (or smoothing) and plumping (or plumping) effect on the lips and the surrounding area, notably improving the smooth, soft and full appearance of the lips. However, it is noted that the combination of at least one high molecular weight non-cross-linked hyaluronic acid and at least one low molecular weight non-cross-linked hyaluronic acid does not provide the desired performance, and the cross-linking of the high molecular weight hyaluronic acid plays an essential role.

[0008] The particular combination of hyaluronic acid according to the invention is therefore particularly advantageous for providing both a moisturizing and a rapid smoothing effect on the skin and / or lips, thus preventing and / or reducing the signs of ageing on the skin and / or providing a volumizing, lifting and smoothing effect on the lips, as well as preventing and / or reducing the appearance of wrinkles. Summary of the Invention

[0009] The first aspect of the present invention relates to a cosmetic composition comprising a combination of at least one high molecular weight cross-linked hyaluronic acid or one of its salts having a molecular weight of 2000 kDa or more and a low molecular weight non-cross-linked hyaluronic acid or one of its salts having a molecular weight of 300 kDa or less in a physiologically acceptable medium.

[0010] Preferably, the cosmetic composition is characterized in that the high molecular weight cross-linked hyaluronic acid has a molecular weight of 3000 kDa or more.

[0011] Preferably, the cosmetic composition is characterized in that the low molecular weight non-crosslinked hyaluronic acid has an average molecular weight of 200 kDa or less.

[0012] Preferably, the cosmetic composition is characterized in that the high molecular weight crosslinked hyaluronic acid has the INCI name SODIUM HYALURONATE CROSSPOLYMER.

[0013] Preferably, the cosmetic composition is characterized in that the low molecular weight non-crosslinked hyaluronic acid is selected from products having the INCI names SODIUM HYALURONATE and HYALURONIC ACID.

[0014] Preferably, the cosmetic composition is characterized in that the high molecular weight crosslinked hyaluronic acid has a crosslinking ratio of 0.001% to 5%, preferably 0.1% to 1%, preferably 0.1% to 0.6%.

[0015] Preferably, the cosmetic composition is characterized in that the high molecular weight crosslinked hyaluronic acid and the low molecular weight non-crosslinked hyaluronic acid are each present in the composition in an amount of 0.001 to 10% by weight, preferably 0.005 to 5% by weight, more preferably 0.01 to 1% by weight, based on the total weight of the composition.

[0016] Preferably, the cosmetic composition further comprises at least one cosmetic adjuvant selected from the group consisting of antioxidants, emollients, moisturizers, anti-aging agents, fragrances, and mixtures thereof.

[0017] Preferably, said cosmetic composition is characterised in that it contains less than 5% fillers, in particular less than 2% fillers, preferably less than 1% fillers or is devoid (or free) of fillers.

[0018] Preferably, the cosmetic composition is in the form of a topical composition for the skin and / or lips, in particular in the form of a cream, an oil-in-water or water-in-oil emulsion or multiple emulsion, a suspension, a gel, a milk, a lotion, a serum, a mask or a lip balm.

[0019] According to another aspect, the present invention relates to a cosmetic method for caring for keratinous materials, in particular the skin and / or the lips, which comprises the topical application to said keratinous materials of at least one layer of a composition as defined above.

[0020] Preferably, said cosmetic method is characterized in that it is intended to promote the moisturization of keratinous substances and / or a rapid smoothing effect of keratinous substances, in particular of the skin and / or lips, and / or to increase the firmness and / or elasticity and / or density and / or volume of keratinous substances, thereby preventing and / or reducing the signs of skin ageing, in particular the loss of firmness and / or elasticity and / or density and / or volume of the skin and / or lips, and / or the appearance of wrinkles, in particular at the lip contour and / or lip lines or simply wrinkles.

[0021] Preferably, said cosmetic method is characterized in that said composition is applied to healthy subjects exhibiting signs related to ageing of the skin and / or lips, in particular loss of firmness and / or elasticity and / or density and / or volume of the skin and / or lips and / or wrinkles in the skin and / or lip contour and / or thin lips and / or lips with vertical wrinkles.

[0022] According to another aspect, the present invention relates to the cosmetic use of at least one crosslinked hyaluronic acid or one of its salts of high molecular weight having a molecular weight of 2000 kDa or more, preferably 3000 kDa or more, and a low molecular weight non-crosslinked hyaluronic acid or one of its salts of low molecular weight having a molecular weight of 300 kDa or less, as an active ingredient combination, for providing a rapid smoothing effect on keratinous materials, in particular for the skin and / or lips. [Brief description of the drawings]

[0023] [Figure 1] FIG. 1 shows the in vivo effect of the hydrating and fast smoothing effect of a hyaluronic acid combination according to the present invention. [Diagram 2] Three representative areas investigated during clinical evaluation by the expert panel are shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] Specific hyaluronic acid combinations according to the present invention According to a first aspect, the present invention relates to a combination of at least one high molecular weight cross-linked hyaluronic acid and one low molecular weight non-cross-linked hyaluronic acid.

[0025] Surprisingly, Applicants have found that the combination of these two particular hyaluronic acids in the same cosmetic composition provides a synergistic effect, thereby enhancing the benefits that each of these hyaluronic acids provides individually.

[0026] According to one embodiment, the hyaluronic acid used according to the invention is embodied in the cosmetic composition in the form of a powder or gel.

[0027] When hyaluronic acid is in powder form, it is usually present at 100% active ingredient.

[0028] When the hyaluronic acid is in gel form, it is usually present in a content ranging from 0.1 to 10% by weight, with the weight percentage of active substance being based on the total weight of the gel.

[0029] "Hyaluronic acid" or "HA" refers to a polymer formed by repeating disaccharide monomers, consisting of glucuronic acid and N-acetylglucosamine linked by alternating β-1,4 and β-1,3 glucosidic bonds. Hyaluronic acid macromolecules naturally exist in linear form, but can also exist in cross-linked form. "Cross-linked hyaluronic acid" refers to hyaluronic acid chains linked by covalent or ionic bonds to form a regular three-dimensional network. Cross-linked hyaluronic acid can be produced with different cross-linking degrees for different applications. Cross-linked polymers based on hyaluronic acid can be obtained by methods well known to those skilled in the art. Representative examples of cross-linkers currently used to produce cross-linked hyaluronic acid are divinyl sulfone (DVS), 1,4-butanediol diglycidyl ether, water-soluble carbodiimide, and cross-linkers with several amine groups.

[0030] By "hyaluronate" is meant in particular sodium hyaluronate, potassium hyaluronate, and other cosmetically acceptable hyaluronates.

[0031] Hyaluronic acid polymers can be of various sizes, depending, among other things, on the number of repeats and the degree of crosslinking. Typically, hyaluronic acid has a molecular weight ranging from several thousand daltons to several million daltons, e.g., 10 3 ~10 7 Da, i.e., a molecular weight of 1 to 10,000 kDa.

[0032] High molecular weight cross-linked hyaluronic acid Thus, the active ingredient combination according to the invention comprises at least one high molecular weight cross-linked hyaluronic acid or one of its salts.

[0033] According to the present invention, the high molecular weight crosslinked hyaluronic acid has a degree of crosslinking in the range of 0.001% to 5%, preferably 0.01% to 1%, and most preferably 0.1% to 0.6%.

[0034] According to the present invention, hyaluronic acid is referred to as "high molecular weight hyaluronic acid" when it has a molecular weight of 1000 kDa or more, preferably 1200 kDa or more, preferably 1400 kDa or more, preferably 2000 kDa or more, for example 3000 kDa or more.

[0035] According to the present invention, the molecular weight or molecular mass of hyaluronic acid refers to the "average" molecular mass (or average molecular weight) of the hyaluronic acid molecules that constitute the raw material used. In fact, the raw material used as the source of hyaluronic acid contains hyaluronic acid polymers whose molar mass may vary slightly. Such variation in molecular mass is particularly related to the fact that the number of basic units (i.e. disaccharide monomers) contained in the hyaluronic acid molecule during polymerization varies slightly. Thus, "molar mass of hyaluronic acid" or "average molar mass of hyaluronic acid" should be understood to mean that the molar mass is the "approximate" mass indicated. In particular, the molar mass of hyaluronic acid indicated may vary by ±20%, preferably ±15% and more preferably ±10%.

[0036] Thus, according to the present invention, reference to a hyaluronic acid having a molar mass of 1000 kDa means that the average molar mass of said hyaluronic acid is approximately 1000 kDa, but this may be between 800 and 1200 kDa, preferably between 850 and 1150 kDa, and preferably between 900 and 1100 kDa.

[0037] According to one embodiment, the high molecular weight crosslinked hyaluronic acid used in the present invention is in the form of a gel. According to this embodiment, the high molecular weight crosslinked hyaluronic acid used in the present invention is preferably a product marketed by Bloomage Freda Biopharm Co., Ltd. under the name "Phylcare® Hyacross® TL 100". "Phylcare® Hyacross® TL 100" is a hyaluronic acid gel containing 1-5% by weight of active ingredient relative to the total weight of the product. The hyaluronic acid polymer used in the composition of this product has a molar mass in the range of 1000 kDa to 1800 kDa. The product "Phylcare® Hyacross® TL 100" is referred to under the International System of Nomenclature of Cosmetic Ingredients (INCI) as SODIUM HYALURONATE CROSSPOLYMER, PENTYLENE GLYCOL, AQUA.

[0038] According to another embodiment, the high molecular weight crosslinked hyaluronic acid used in the present invention is in the form of powder. According to this embodiment, the high molecular weight crosslinked hyaluronic acid used in the present invention is preferably a product with the commercial name "Phylcare® Hyacross® TL 200" produced by Bloomage Freda Biopharm Co., Ltd. "Phylcare® Hyacross® TL 200" is a hyaluronic acid in powder form that is 100% pure, i.e., composed of 100% active ingredients. The hyaluronic acid polymer used in the composition of this product has a molar mass of 3000 kDa or more. The product "Phylcare® Hyacross® TL 200" is referred to as SODIUM HYALURONATE CROSSPOLYMER under the International System of Nomenclature of Cosmetic Ingredients (INCI).

[0039] In its capacity as a cosmetically active ingredient, the high molecular weight crosslinked hyaluronic acid is present in the cosmetic compositions of the present invention in an amount effective to achieve the desired benefit.

[0040] In particular, the high molecular weight crosslinked hyaluronic acid, preferably the product having the commercial name "Phylcare® Hyacross® TL 200", is present in a content ranging from 0.001 to 10% by weight, preferably 0.005 to 5% by weight, more preferably 0.01 to 1% by weight, in terms of the weight of the raw material (weight of the product) relative to the total weight of the composition.

[0041] Low molecular weight non-crosslinked hyaluronic acid The active ingredient combination according to the invention also comprises at least one low molecular weight non-crosslinked hyaluronic acid or one of its salts.

[0042] According to the present invention, hyaluronic acid is termed "low molecular weight hyaluronic acid" when it has a molecular weight of less than 500 kDa, preferably less than 400 kDa, preferably less than 300 kDa.

[0043] According to one embodiment, the low molecular weight hyaluronic acid used in combination according to the present invention has a molecular weight of 500 kDa or less, preferably 400 kDa or less, preferably 300 kDa or less, and preferably 50 kDa or more, preferably 100 kDa or more.In particular, according to one embodiment, its molecular weight is in the range of 100 kDa to 300 kDa.

[0044] According to one embodiment, the low molecular weight hyaluronic acid used in combination according to the present invention has a molecular weight of 200 kDa or less, preferably 150 kDa or less, preferably 100 kDa or less, and preferably 10 kDa or more, preferably 50 kDa or more.In particular, according to one embodiment, its molecular weight is in the range of 10 kDa to 100 kDa.

[0045] According to one embodiment, the low molecular weight hyaluronic acid used in combination according to the present invention has a molecular weight of 100 kDa or less, preferably 50 kDa or less, preferably 10 kDa or less, and preferably 1 kDa or more, preferably 5 kDa or more.In particular, according to one embodiment, its molecular weight is in the range of 5 kDa to 10 kDa.

[0046] According to the invention, such low molecular weight non-crosslinked hyaluronic acid may be in the form of a gel or in the form of a powder. Advantageously, it is in the form of a powder.

[0047] According to one embodiment, the low molecular weight non-crosslinked hyaluronic acid used in the present invention is a product marketed by the company Soliance under the name "Bashyal powder". The "Bashyal powder" product is hyaluronic acid in powder form that is 100% pure, i.e. composed of 100% active ingredients. The hyaluronic acid polymers used in the composition of this product have a molar mass ranging from 100 kDa to 300 kDa. "Bashyal powder" is referred to as SODIUM HYALURONATE under the International System of Nomenclature (INCI).

[0048] According to one embodiment, the low molecular weight non-crosslinked hyaluronic acid used in the present invention is a product marketed by the company Givaudan under the name "PRIMALHYAL ULTRAFILLER". The product "PRIMALHYAL ULTRAFILLER" is a hyaluronic acid in powder form that is 100% pure, i.e., composed of 100% active ingredients. The hyaluronic acid polymers used in the composition of this product have an average molar mass of less than 15 kDa. "PRIMALHYAL ULTRAFILLER" is called SODIUM ACETYL HYALURONATE under the International System of Nomenclature (INCI).

[0049] According to another embodiment, the low molecular weight non-crosslinked hyaluronic acid used in the present invention is a product marketed by the company Sochibo under the name "Oligo HA". The "Oligo HA" product is a hyaluronic acid in powder form that is 100% pure, i.e., composed of 100% active ingredients. The hyaluronic acid polymers used in the composition of this product have a molar mass in the range of 5 kDa to 10 kDa. "Oligo HA" is referred to as HYALURONIC ACID under the International System of Nomenclature (INCI).

[0050] In its capacity as a cosmetically active ingredient, the low molecular weight non-crosslinked hyaluronic acid is present in the cosmetic compositions of the present invention in an amount effective to achieve the desired benefit.

[0051] In particular, the low molecular weight non-crosslinked hyaluronic acid, preferably the product having the commercial name "Bashyal powder" or the product having the commercial name "Oligo HA" or the product having the commercial name "PRIMALHYAL ULTRAFILLER", is present in a content ranging from 0.001 to 10% by weight, preferably 0.005 to 5% by weight, more preferably 0.01 to 1% by weight, in terms of the weight of the raw material (weight of the product) relative to the total weight of the composition.

[0052] Cosmetic and galenic compositions according to the invention In the context of the present invention, the above-mentioned hyaluronic acid combinations are particularly used for the preparation of cosmetic compositions, in particular cosmetic compositions suitable for topical application to keratinous materials, especially on the skin, preferably on the face and / or neck and / or lips.

[0053] Thus, according to another aspect, the present invention relates to a cosmetic composition comprising, in a physiologically acceptable medium, a combination of at least one high molecular weight cross-linked hyaluronic acid or one of its salts as defined above and at least one low molecular weight non-cross-linked hyaluronic acid or one of its salts as defined above.

[0054] By "cosmetic composition" is meant a composition for cosmetic (or cosmetic) or aesthetic purposes, which may come into contact with the keratinous materials of the superficial parts of the human body, and more particularly, in particular the human skin and / or lips.

[0055] By "physiologically acceptable medium" is meant any additive (or excipient) suitable for topical use in contact with keratinous materials and which does not pose a risk of toxicity, incompatibility, instability and / or allergic reaction.

[0056] By "keratinous material" according to the invention is meant the skin and / or its appendages, and more particularly the human skin and / or lips. In particular, this concerns the skin of the face and / or neck and / or body, and the lips.

[0057] According to one embodiment, the composition according to the invention comprises a high molecular weight crosslinked hyaluronic acid having the INCI name SODIUM HYALURONATE CROSSPOLYMER, PENTYLENE GLYCOL, AQUA, in particular the active ingredient marketed under the name "Phylcare® Hyacross™ TL 100" produced by Bloomage Freda Biopharm Co., Ltd.

[0058] According to one embodiment, the composition according to the invention comprises a high molecular weight crosslinked hyaluronic acid having the INCI name SODIUM HYALURONATE CROSSPOLYMER, in particular the active ingredient marketed under the name "Phylcare® Hyacross® TL 200" produced by Bloomage Freda Biopharm Co., Ltd.

[0059] According to one embodiment, the composition according to the invention comprises a low molecular weight non-crosslinked hyaluronic acid having the INCI name SODIUM HYALURONATE, in particular the active ingredient marketed under the name "Bashyal powder" by the company Soliance.

[0060] According to another embodiment, the composition according to the invention comprises a low molecular weight non-crosslinked hyaluronic acid having the INCI name HYALURONIC ACID, in particular the active ingredient marketed under the name "Oligo HA" by the company Sochibo.

[0061] According to a preferred embodiment, the composition according to the invention comprises, in a physiologically acceptable medium: High molecular weight crosslinked hyaluronic acid, in particular the active ingredient having the trade name "Phylcare® Hyacross® TL 200" produced by Bloomage Freda Biopharm Co., Ltd. and having the INCI name SODIUM HYALURONATE CROSSPOLYMER, Low molecular weight non-crosslinked hyaluronic acid, in particular the active ingredient with the trade name "Bashyal powder" by Soliance, which has the INCI name SODIUM HYALURONATE. Includes.

[0062] According to another preferred embodiment, the composition according to the invention comprises, in a physiologically acceptable medium: High molecular weight crosslinked hyaluronic acid, in particular the active ingredient having the trade name "Phylcare® Hyacross® TL 200" produced by Bloomage Freda Biopharm Co., Ltd. and having the INCI name SODIUM HYALURONATE CROSSPOLYMER, Low molecular weight non-crosslinked hyaluronic acid, in particular an active ingredient with the trade name "Oligo HA" by Sochibo, which has the INCI name HYALURONIC ACID. Includes.

[0063] The cosmetic composition according to the present invention contains the above-mentioned hyaluronic acid, that is, high molecular weight crosslinked hyaluronic acid and low molecular weight non-crosslinked hyaluronic acid, in an amount effective to obtain a desired effect.

[0064] In one embodiment, the composition according to the present invention contains the high molecular weight crosslinked hyaluronic acid and the low molecular weight non-crosslinked hyaluronic acid in a content of 0.001 to 10% by weight, preferably 0.005 to 5% by weight, and more preferably 0.01 to 1% by weight, expressed as a percentage by weight of the raw material (product weight) relative to the total weight of the composition.

[0065] According to one embodiment, each of the hyaluronic acids used in the present invention is present in the composition at a content ranging from 0.05 to 0.8% by weight, more preferably 0.1 to 0.6% by weight, in terms of the weight of the raw material (product weight) relative to the total weight of the composition.

[0066] When hyaluronic acid is dispersed in a gel-forming solvent, it is present in the composition in a content ranging from 0.1 to 10% by weight, more preferably 1 to 5% by weight, of active substance (hyaluronic acid polymer) relative to the total weight of the composition.

[0067] Advantageously, the cosmetic composition according to the present invention comprises the high molecular weight crosslinked hyaluronic acid and the low molecular weight non-crosslinked hyaluronic acid in a ratio of high molecular weight crosslinked hyaluronic acid / low molecular weight non-crosslinked hyaluronic acid (by weight of raw materials) comprised between 0.01 and 100, preferably between 0.1 and 10, most preferably between 0.5 and 2.

[0068] In terms of weight of active substance of hyaluronic acid polymers, the ratio of high molecular weight crosslinked hyaluronic acid to low molecular weight non-crosslinked hyaluronic acid is in the range of 0.1-10, particularly 0.5-2.

[0069] In one embodiment, the cosmetic composition according to the invention is a care and / or makeup composition for keratin substances, in particular for the skin, preferably for the skin of the face and / or neck and / or lips.

[0070] According to a preferred embodiment, the cosmetic composition according to the invention is a composition for the care of keratinous substances, in particular for the skin, preferably for the skin of the face and / or neck and / or lips.

[0071] The cosmetic compositions of the present invention comprise at least a high molecular weight crosslinked hyaluronic acid and a low molecular weight non-crosslinked hyaluronic acid as defined above, and additionally comprise one or more acceptable cosmetic additives (or excipients) known to those skilled in the art with a view to providing a composition for topical application.

[0072] The present invention thus relates to a composition, in particular a cosmetic composition, in the form of a topical composition for the skin and / or lips, in particular in the form of a cream, an oil-in-water or water-in-oil emulsion or multiple emulsion, a suspension, a gel, a milk, a lotion, a serum, a mask or a lip balm.

[0073] The compositions of the present invention may also further comprise at least one cosmetic adjuvant selected from the group consisting of antioxidants, emollients, moisturizers, anti-aging agents (or anti-aging agents), fragrances, and mixtures thereof.

[0074] The cosmetic adjuvants advantageously used in the composition of the invention may be present in a content ranging from 0.001 to 10% by weight, and preferably from 0.001 to 5% by weight, relative to the total weight of the composition.

[0075] According to one embodiment, the composition of the invention may advantageously comprise one or more cosmetic ingredients comprising one or more polyglycerins having between 3 and 10 glycerol units, preferably chosen from the products with the INCI names Polyglycerin-3 and Polyglycerin-6.

[0076] As cosmetic ingredients based on polyglycerol that can be used according to the invention, mention may in particular be made of the following products sold by the company SAKAMOTO: PGL-S, INCI name Polyglycerin-3 POLYGLYCERIN 310, INCI name Polyglycerin-4 POLYGLYCERIN-500 MB, INCI name Polyglycerin-6 and water (AQUA (WATER)) POLYGLYCERIN-750 MB, INCI name Polyglycerin-10 and water (AQUA (WATER))

[0077] The Applicant has been able to demonstrate that the lip plumping effect, in particular a fast and / or long-lasting plumping effect, can be further improved by using polyglycerol, in particular in combination with at least one high molecular weight cross-linked hyaluronic acid or one of its salts as defined above and at least one low molecular weight non-cross-linked hyaluronic acid or one of its salts as defined above.

[0078] According to one embodiment, the cosmetic composition of the invention comprises at least 0.5% polyglycerin, in particular at least 1% polyglycerin, preferably at least 2% polyglycerin, in particular those selected from the products with the INCI names Polyglycerin-3 and Polyglycerin-6.

[0079] According to one embodiment, the cosmetic composition of the invention comprises less than 10% polyglycerin, in particular less than 8% polyglycerin, preferably less than 6% polyglycerin, in particular those selected from the products with the INCI names Polyglycerin-3 and Polyglycerin-6.

[0080] Depending on the nature of the composition, one or more cosmetically acceptable additives (or excipients) may also be selected. Any additives commonly used in the preparation of cosmetic compositions intended for use on keratinous materials can be used in the present invention. Preferably, the cosmetically acceptable additives are selected from polymers, surfactants, rheological agents (or viscosity modifiers), electrolytes, pH modifiers, preservatives (or antiseptics), dyes, nacres, pigments and mixtures thereof.

[0081] According to one embodiment, the cosmetic composition of the invention comprises less than 5% of fillers, in particular less than 2% of fillers, preferably less than 1% of fillers, in particular fillers with a blurring effect.

[0082] However, according to another embodiment of the present invention, the cosmetic composition of the present invention lacks (or does not contain) fillers, particularly those with blurring effect.Indeed, while those with blurring effect can advantageously obtain a quick smoothing effect, increase viscosity, and present a less shiny appearance when applied, these fillers can have an opposite effect on the moisturizing effect of hyaluronic acid.

[0083] "Fillers" means particles of platelet, spherical or ellipsoidal shape, colorless or white, mineral or organic, natural or synthetic, dispersed in insoluble form in the medium of the composition. These fillers function in particular to modify the rheology or texture of the composition and / or to impart a mattifying effect. "Blurring effect" fillers means an effect that can hide the micro-reliefs of the skin and thus dilute, by optical correction effect, imperfections in relief and / or color, such as wrinkles, fine lines, pores, pimples, etc.

[0084] Cosmetic methods and uses The cosmetic methods and cosmetic uses described below are intended to be applied to keratinous materials, in particular healthy keratinous materials, preferably the skin, in particular the skin of the face and / or neck and healthy lips of a "healthy" subject.

[0085] The keratinous material according to the invention is in particular a healthy keratinous material ("healthy" subjects), i.e. does not exhibit conditions or diseases associated with pathological conditions (pathological "unhealthy" subjects). The terms healthy skin and / or lips or skin and / or lips are used interchangeably in the remaining specification.

[0086] Another object of the present invention relates to a cosmetic method for caring for keratinous materials, in particular healthy keratinous materials, especially the skin and / or lips, which comprises the application to said keratinous materials of at least one layer of the cosmetic composition described above.

[0087] In the context of the present invention, said cosmetic method is intended to promote moisturization of keratinous materials, in particular the skin and / or lips.

[0088] In the context of the present invention, the cosmetic method is also intended to provide a rapid smoothing effect on keratinous materials, in particular on the skin and / or lips.

[0089] By "smoothing effect" is meant that the composition according to the invention is capable of reducing the roughness (or unevenness) and / or microrelief of the skin. By "rapid smoothing effect" is meant that the composition according to the invention is capable of providing a smoothing effect within one hour after application of the composition.

[0090] Thus, in particular due to the effect of the composition on moisturization, roughness and microrelief of the skin, the cosmetic method of the invention makes it possible to reduce the signs of aging (or ageing or aging) of the skin.

[0091] In the context of the present invention, said cosmetic method is intended to promote firmness and / or elasticity of keratinous materials, in particular the skin and / or lips, and thus prevent and / or reduce skin ageing, and in particular prevent and / or reduce the appearance of wrinkles.

[0092] The cosmetic method of the present invention therefore also has particularly interesting anti-aging properties.

[0093] According to another aspect, the present invention relates to the cosmetic use of a combination of at least one high molecular weight crosslinked hyaluronic acid as defined above and one low molecular weight non-crosslinked hyaluronic acid as active ingredients, for providing a rapid smoothing effect on keratinous materials, in particular the skin and / or lips.

[0094] According to one preferred embodiment, the composition used in the cosmetic method and use according to the invention comprises: High molecular weight crosslinked hyaluronic acid, in particular the active ingredient having the trade name "Phylcare® Hyacross® TL 200" produced by Bloomage Freda Biopharm Co., Ltd. and having the INCI name SODIUM HYALURONATE CROSSPOLYMER, Low molecular weight non-crosslinked hyaluronic acid, in particular the active ingredient with the trade name "Bashyal powder" by Soliance, which has the INCI name SODIUM HYALURONATE. Includes.

[0095] According to another preferred embodiment, the composition used in the cosmetic method and use according to the invention comprises: High molecular weight crosslinked hyaluronic acid, in particular the active ingredient having the trade name "Phylcare® Hyacross® TL 200" produced by Bloomage Freda Biopharm Co., Ltd. and having the INCI name SODIUM HYALURONATE CROSSPOLYMER, Low molecular weight non-crosslinked hyaluronic acid, in particular an active ingredient with the trade name "Oligo HA" by Sochibo, which has the INCI name HYALURONIC ACID. Includes.

[0096] According to one embodiment, the composition of the present invention is applied to a healthy subject having dry skin.

[0097] According to one embodiment, the compositions of the present invention are applied to healthy subjects exhibiting a loss of skin firmness and / or elasticity.

[0098] According to another particular embodiment, the composition of the invention is applied to healthy subjects showing signs related to skin aging, in particular wrinkles.

[0099] According to one embodiment, the composition of the present invention is applied to healthy subjects having dry and / or thin lips and / or lips exhibiting vertical lines and / or wrinkles at the lip contour.

[0100] The invention is illustrated in the following non-limiting examples. Unless otherwise stated, percentages are given by weight of ingredient relative to the total weight of the composition. EXAMPLES

[0101] Example 1: Study on the rapid skin smoothing effect 1-1 Research Procedure Research purpose The purpose of this study was to evaluate and compare the rapid smoothing effect (before application and 1 hour after application) of one or more products on a microrelief network or MRN by skin replica technique.

[0102] The rapid smoothing effect of the different products was evaluated on male or female volunteers, all over 35 years of age, without any skin conditions in the area being evaluated.

[0103] measurement principles At different times during the study, replicas of the skin surface are taken. These replicas are imprints of the skin surface and are used to evaluate the cosmetic effect of the active ingredients tested. These replicas are processed by image analysis using Quantilines software.

[0104] The replica is taken by applying one adhesive ring with a diameter of 24 mm to the test area. Then, using a spatula, Silflo silicone casting resin (Flexico) plus catalyst (Flexico) is spread inside this ring. After drying, the replica is peeled off from the skin surface.

[0105] The replica is illuminated with a grazing illuminator at an incidence angle of 35° to generate shadows behind each line (wrinkle) on the surface of the skin. These shadows are then analyzed on a video image of the replica using Quantilines software, which calculates parameters that describe the skin surface.

[0106] Position the replica relative to the light source to maximize shadows (north-south orientation).

[0107] Replicas taken after treatment are precisely rearranged relative to those taken before treatment.

[0108] The surface of the replica is divided into 90 equidistant lines, for each of which the software calculates the following parameters: · Ra is the average roughness, which is the ratio of the integrated area of ​​the length profile to the length of the profile. The average Ra is the arithmetic mean of the Ra values ​​(in arbitrary units) of all the profiles. · Rzis the average amplitude of the peaks in the profile under consideration. Divide each profile into 5 segments of equal length and calculate the amplitude Rzi of the peaks for each segment. The arithmetic mean of the Rzi values ​​(in arbitrary units) of all profiles is the average Rz. · Rm is the maximum roughness (the maximum roughness among the five segments analyzed). · Area : corresponds to the factor between the actual length of the skin and the length that can be seen of the skin. It is responsible for smoothing the skin and highlighting micro-wrinkles. The more micro-wrinkles the skin has, the increased the area. The result is displayed in % in the "Area" result window.

[0109] Measurements were taken on the skin of the forearm before and one hour after application of the products to be evaluated. The products to be evaluated were administered by technicians at a concentration of 2 μL / cm 2 I spread it out in an amount of 100%.

[0110] Evaluation items The primary endpoints were Rm, Rz, Ra and area.

[0111] These parameters are decreased when the treatment has a beneficial effect on the smoothing of the skin. A product is said to have a smoothing effect on the skin when at least two of the main evaluation items are significantly (or markedly) decreased.

[0112] The differences between the values ​​before application and 1 hour after application are calculated for each parameter, each volunteer and each product. These differences are compared by analysis of variance. If they are significant (or noticeable), the products are classified using the Newman-Keuls test.

[0113] statistical analysis The statistical method used is the analysis of variance (ANOVA). The data are assumed to follow a normal distribution. With ANOVA, the Student-Newman-Keuls test is performed for multiple comparisons of means and for the determination of similar groups. Sample size: A sufficient number of volunteers should be included to allow evaluation of 12 subjects. Significance level: Alpha risk of 5% or less Calculation method: · Product effects on the skin For each parameter and each product, the time before (t0) and after (t i Calculation and comparison of means of Calculate the percentage change using the following formula: VAR i %=(P i -P0) / P0×100 During the ceremony, P0: Mean of the parameters of the treated area at time T0 P i : Time T i Average of the parameters of the treated area in Percentages are calculated only if differences are significant compared to pre-treatment values.

[0114] 1-2: Commercial references for cosmetic active ingredients used in the examples High Molecular Weight Hyaluronic Acid " Hyacross TL200 " The commercial product "Phylcare® Hyacross® TL 200" produced by Bloomage Freda Biopharm Co., Ltd. has the INCI name SODIUM HYALURONATE CROSSPOLYMER. Cross-linked hyaluronic acid with a molecular weight of 3000 kDa or more " HMW Sodium Hyaluronate " The commercial product produced by Sochibios is "Bio-sodium hyaluronate powder" and has the INCI name SODIUM HYALURONATE. Non-crosslinked hyaluronic acid with an average molecular weight in the range of 1000 kDa to 1500 kDa

[0115] Low molecular weight non-crosslinked hyaluronic acid " Bashyal " The commercial product "Bashyal powder" produced by Soliance has the INCI name SODIUM HYALURONATE. Hyaluronic acid with an average molecular weight in the range of 100 kDa to 300 kDa " Oligo HA " The commercial product produced by Sochibo is "Oligo HA" and has the INCI name HYALURONIC ACID. Hyaluronic acid with an average molecular weight in the range of 5 kDa to 10 kDa

[0116] Whether used alone or in combination, these active ingredients were used in the examples at individual concentrations ranging from 0.3 to 0.5% by weight of the ingredient based on the total weight of the composition.

[0117] 1-3: Formulations to be evaluated [Table 1]

[0118] Different hyaluronic acids, high and low molecular weight, cross-linked or non-cross-linked, were tested alone or in combination in the above formulations.

[0119] [Table 2]

[0120] The placebo was a simple formulation consisting of water, glycols, and preservatives. A viscosity modifier (Carbopol Ultrez 20 = acrylates / C10-30 alkyl acrylate crosspolymer, neutralized with sodium hydroxide to pH approx. 6) was added to obtain similar viscosities between the different tests. The amount of thickener was adjusted to maintain comparable viscosities in the different formulations.

[0121] Formulation Preparation Process a. Heat Phase A to 80°C (water + preservatives) b. Add Carbopol Ultrez 20 to Phase A and deflocculate at 300 RPM until no particles remain. c. Add 10% sodium hydroxide solution to Phase A at 500 RPM until a gel forms. d. Weigh out glycols (glycerin / butylene glycol / propanediol / pentylene glycol) into capsules e. Wet the hyaluronic acid (HA) into the glycolic mixture until a homogenous paste is formed. f. Add the glycols / HA mixture from step (e) to phase A from step (c) at 60° C. and deflocculate at 600 RPM. g. Cool to 30℃ while deflocculating at 400RPM h. Stop motor and water compensation

[0122] 1-4: Research results on rapid smoothing effects The results of this study are shown in Figure 1.

[0123] Surprisingly, it has been observed that certain combinations of certain types of hyaluronic acid exhibit synergistic effects for rapid smoothing effects.

[0124] In particular, the combination of a low molecular weight hyaluronic acid such as "Bashyal" or "Oligo HA" with a high molecular weight cross-linked hyaluronic acid such as "Hyacross TL 200" can provide a significant (or noticeable) rapid smoothing effect.

[0125] Furthermore, it has been observed that the combination of these same low molecular weight hyaluronic acids with high molecular weight non-crosslinked hyaluronic acids such as "high molecular weight Na hyaluronate" fails to achieve this rapid smoothing effect.

[0126] Thus, these results surprisingly demonstrate that cross-linking of high molecular weight hyaluronic acid polymers is essential to obtain a rapid smoothing effect.

[0127] Example 2: Skin moisturization study 1-1 Research Procedure Research purpose The purpose of this study was to evaluate and compare the short-term moisturizing effect (6 and 24 hours) of one or more products by measuring the variations in skin capacitance and impedance using a corneometer.

[0128] The moisturizing effects of the different products were evaluated in male or female volunteers, all aged 18 years or older, without any skin conditions in the areas being evaluated.

[0129] measurement principles The Corneometer measures the change in capacitance (change in the dielectric constant of the skin) as a function of the water content of the skin. The sensor consists of two electrodes, which are used to generate an electric field at the skin surface. The capacitance of the electrode system and the skin is affected by the change in the dielectric constant of the biological medium with which the probe is in contact. The more moisturized the skin, the higher the dielectric constant. An alternating current is applied to the electrodes. The time required to reach a given potential difference is proportional to the inverse of the capacitance of the system, and the increase in the dielectric constant of the stratum corneum is recorded by the Corneometer as an increase in the frequency of the alternating current. The capacitance change is expressed in arbitrary units.

[0130] Impedance indicates the degree of hydration of the upper layers of the epidermis. The dielectric constant of the skin is related to the water content of the skin. Measurement of electrical properties is recognized as an objective method to evaluate the hydration of the stratum corneum (E. Berardesca - EEMCO guidance for the assessment of stratum corneum hydration: electrical methods - Skin Research and Technology 1997; 3: 126-132).

[0131] The corneometer measures the skin capacitance Cx, which is part of the equation that defines impedance. Z=[Rx 2 +(1 / 2πfCx) 2 ] 1 / 2 During the ceremony, Z: Impedance Rx: Low efficiency (Low efficiency = 1 / conductivity) f: AC frequency Cx: Capacity

[0132] Measurements are performed on the forearm and the area is protected from friction between measurements by a ring held in place by a hypoallergenic, stretchy, non-occlusive, adhesive fabric (Hypafix, Smith & Nephew), which is removed immediately prior to a 15 minute stabilization period.

[0133] After a stabilization period of 15 minutes, three successive measurements are carried out with the corneometer, allowing the area to be adjusted to the ambient atmospheric conditions of the measurement room (temperature 22°C ± 2°C and relative humidity 50% ± 10%).

[0134] No skin preparation is performed. The product to be tested is applied by the technician at 2 μL / cm before the start of the measurement. 2 is applied at once.

[0135] On the morning of the study (before the measurements), the volunteers used only their usual personal care products. No other products were to be used during the study.

[0136] Evaluation items Capacitance is expressed in arbitrary units on a scale of approximately 0 to 150. The higher the value, the more moisturizing it is.

[0137] statistical analysis The statistical method used is the analysis of variance (ANOVA). The data are assumed to follow a normal distribution. With ANOVA, the Student-Newman-Keuls test is performed for multiple comparisons of means and for the determination of similar groups. Sample size: A sufficient number of volunteers should be included to allow for evaluation of 10 subjects. Significance level: Alpha risk of 5% or less Calculation method: · Untreated areas are considered product. Analytical factors: volunteers, time of measurement and product 1. In the overall ANOVA, all factors are combined with the raw data. A graph of the residuals is useful for detecting outliers (or abnormal values). 2. Calculate the average of the three measurements: Grouping of Averages. 3. In the entire ANOVA, all factors are combined with their means to test for groupings (comparing the mean with 1). 4. ANOVA on the mean values ​​for all products & volunteers combined with T0 to compare the measurement sites at T0 (before application). 5. Calculate the change by comparing with the value before application: T i -T0 (=ΔT) During the ceremony, T i :t i Moisturizing with T0: Moisturizing the same area at t0 6. ANOVA for ΔT combines all products & volunteers with each measurement time to compare products at each time. 7. In the overall ANOVA for ΔT, all factors are combined (except T0) to compare products together overall. Products may not be considered in this analysis in order to compare them more strictly with other products. 8. a) Calculate percentages to compare the effectiveness of different products in relation to untreated areas. Only when the difference compared to an untreated area (or reference) is significant. Percentages are calculated for each volunteer.

number

[0138] 2-2: Commercial references for cosmetic active ingredients used in the examples The commercial references used in this example are the same as those in Examples 1-2 above.

[0139] 2-3: Formulations to be evaluated The formulations evaluated in this example are the same as in Examples 1-3 above.

[0140] 2-4: Research results on moisturizing effects The results of this study are shown in Figure 1.

[0141] Surprisingly, it has been observed that certain combinations of certain types of hyaluronic acid exhibit synergistic moisturizing effects.

[0142] 6 and 24 hour moisturization The results show that for the placebo composition and for the compositions containing only one of the hyaluronic acids "Bashyal" or "Hyacross TL 200" (comparison), the measured moisturization is between 13% and 22% at 6 hours and between 14% and 21% at 24 hours (Figure 1).

[0143] Surprisingly, the results show that for a composition (according to the invention) comprising the combination "Bashyal" + "Hyacross TL 200", the moisturization is 34% at 6 hours (compared to 13-22% in comparison) and 28% at 24 hours (compared to 14-21% in comparison) (Figure 1).

[0144] For example, an improvement in moisturization can be obtained by combining a low molecular weight hyaluronic acid such as "Bashyal" with a high molecular weight cross-linked hyaluronic acid such as "Hyacross TL 200" (according to the present invention).

[0145] Furthermore, it has been observed that the combination of "Bashyal" with high molecular weight non-crosslinked hyaluronic acid such as "High molecular weight Na hyaluronate" (comparison) fails to obtain such improvements.

[0146] 6 and 24 hour total insensible water loss (TEWL) The results show that for the placebo composition and the composition containing only hyaluronic acid "Bashyal" or "Hyacross TL 200" (comparison), the measured insensible perspiration was -12% to -14% at 6 hours and -5% to -13% at 24 hours (Figure 1).

[0147] Surprisingly, the results show that for the composition (according to the invention) comprising the combination of "Bashyal" + "Hyacross TL 200", the insensible perspiration is -21% at 6 hours and -17% at 24 hours (Figure 1).

[0148] The combination of low molecular weight hyaluronic acid, such as "Bashyal", with high molecular weight cross-linked hyaluronic acid, such as "Hyacross TL 200", according to the present invention, can reduce insensible perspiration.

[0149] Furthermore, it has been observed that the combination (comparison) of "Bashyal" with high molecular weight non-crosslinked hyaluronic acid such as "high molecular weight sodium hyaluronate" fails to achieve such effects.

[0150] summary Thus, these results surprisingly show that in the context of a combination of low and high molecular weight hyaluronic acid, cross-linking of the high molecular weight hyaluronic acid polymers is essential to obtain improved moisturizing effects.

[0151] Example 3: Lip plumping and smoothing effect study 3-1 Research Procedure Research purpose The purpose of this study was to evaluate the extent to which a combination of hyaluronic acids according to the present invention could provide plumping and smoothing effects to the lips, lip contour and nasolabial area.To this end, the effects of test formulations comprising a combination of high molecular weight cross-linked hyaluronic acid and low molecular weight non-cross-linked hyaluronic acid were evaluated by a panel of subjects.The formulations are described below.

[0152] Objects included in the study The efficacy was evaluated in female volunteers of European descent. These volunteers (or subjects) were divided into two groups according to the formulation being tested (test formulation and control formulation). · Group 117 volunteers, mean age 45.6±6.7 years (37-57 years) · Group 2 15 volunteers, mean age 47.5±4.9 years (39-56 years)

[0153] The volunteers had all skin types (they were not selected for skin type) and all were users of lip care products. In addition, all volunteers included in the study demonstrated the following: - Wrinkles around the lip contour, Lack of volume in the lips, and Lips that look under-hydrated

[0154] Formulations evaluated to test the effect of hyaluronic acid combinations according to the present invention The formulations tested correspond to a baseline cosmetic formulation against which the cosmetic effect of the active ingredient of interest can be evaluated. This baseline formulation, also referred to as the control composition, is listed in Table 3.

[0155] Table 3: Basic formulation, also referred to as control composition [Table 3]

[0156] During this study, group 2 received a control formulation (CTL formulation) corresponding to the basic cosmetic formulation only, and therefore not containing the hyaluronic acid combination according to the invention.

[0157] On the other hand, group 1 received the test composition (2HA formulation), i.e. a basic cosmetic formulation also containing a combination of hyaluronic acid according to the present invention: " Hyacross TL200 " The commercial product "Phylcare® Hyacross® TL 200" produced by Bloomage Freda Biopharm Co., Ltd. has the INCI name SODIUM HYALURONATE CROSSPOLYMER. Crosslinked hyaluronic acid with a molecular weight of 3000 kDa or more. " PRIMALHYAL ULTRAFILLER " Commercial product "PRIMALHYAL ULTRAFILLER" produced by Givaudan. Hyaluronic acid with an average molecular weight of less than 15 kDa.

[0158] Table 4: 2HA formulations, also referred to as test compositions [Table 4]

[0159] The formulations to be evaluated (control formulation and 2HA formulation) were applied to the lips and lip contour twice daily, morning and evening, for the duration of the study, ie, 28 days.

[0160] 3-2:Results 3.2.1. Research 1 The plumping effect of the tested formulations (described in section 2-1 above) was evaluated by an expert panel immediately after application, then 8 and 24 hours after application, and finally on days 7 and 28 of the study.

[0161] The plumping effect was assessed by measuring the curvature of the upper lip.

[0162] The results show that the 2HA formulation significantly (or noticeably) reduces the curvature of the upper lip immediately after application. The reduction in curvature reflects an increase in lip volume. In addition, unlike the control formulation, this effect is maintained over time, as a significant effect is still observed at 8 hours and 24 hours (control formulation has no significant effect). This effect is also observed at 7 days and 28 days only with the 2HA formulation.

[0163] Thus, the hyaluronic acid combination according to the present invention can advantageously plump the lips upon application and act with proven long-term effectiveness.

[0164] Study 2 – Clinical evaluation As part of the study, clinical evaluations were performed by trained evaluators. The effects of the tested cosmetic formulations (described in Section 2-1 above) were evaluated on three areas of the face, all including the lips. The evaluation criteria were the appearance of the lip area (Zone 1), the appearance of the lip contour area (Zone 2), and the appearance of the larger area surrounding the lips (Zone 3). Zones 1, 2, and 3 are shown in Figure 2.

[0165] [Table 5] T4W = 4 weeks after the start of the study, T0 = at the start of the study, before the first application of the product to be tested, NS = Not Significant (or not significant).

[0166] It is noted that compared to the control formulation, the 2HA formulation provides superior results for all criteria evaluated.

[0167] These results reflect the cosmetic interest of the combination of hyaluronic acid according to the present invention.This combination can advantageously obtain a smoothing and plumping effect on lips and the surrounding area.There is particularly an improvement in the smooth, soft and plump appearance of lips, as well as an improvement in lip health (pink color).It is also noted that it smoothes the wrinkles around the lips, and more generally the skin around the lips.

[0168] 3-3. Summary These studies aimed to evaluate the plumping and smoothing effect of cosmetic compositions containing the hyaluronic acid combination according to the present invention on the lips and the facial area around the lips, and show that the hyaluronic acid combination according to the present invention makes the 2HA formulation more effective in having a long-lasting effect on smoothing, softness and plumping than the control formulation.

[0169] Example 4: Immunostaining study of the effect of the hyaluronic acid combination according to the invention on the expression of fibrillin-1 4-1: Explant preparation Twenty-four explants measuring 12 ± 1 mm in diameter were prepared from the abdomen of a 62-year-old woman of European ancestry, phototype II-III, and placed in BEM (BIO-EC's Explants Medium) in a humid environment at 37 °C enriched with 5% CO2.

[0170] The explants were divided into six batches as follows:

[0171] [Table 6]

[0172] Product Application On days 0, 2, 5, and 6, the products to be tested, P1 to P4, were placed on 1 cm explants. 2 per 2μL (approximately 2mg / cm 2) and spread using a small spatula. Control batches of explants received no treatment except for refreshing the medium. Half of the medium was refreshed (1 mL / well) on days 1, 2, and 5.

[0173] sample On day 0, three explants were removed from the TO batch and cut in half. Each sample was cut in half, one half was frozen in OCT at -80°C, and the other half was fixed in formalin. On day 7, three explants were removed from each batch and given the same treatment as on day 0.

[0174] 4-2: Commercial references for cosmetic active ingredients used in the examples The commercial references used in this example are the same as those in Examples 1-2 above.

[0175] 4-3: Formulations to be evaluated [Table 7]

[0176] Different hyaluronic acids, high and low molecular weight, cross-linked or non-cross-linked, were tested alone or in combination in the above formulations.

[0177] [Table 8]

[0178] The placebo was a simple formulation consisting of water, glycols, and preservatives. A viscosity modifier (Carbopol Ultrez 20 = acrylates / C10-30 alkyl acrylate crosspolymer, neutralized with sodium hydroxide to pH approx. 6) was added to obtain similar viscosities between the different tests. The amount of thickener was adjusted to maintain comparable viscosities in the different formulations.

[0179] 4-4: Research results on the expression of fibrillin-1 Fibrillin-1 immunostaining Fibrillin-1 was labeled in frozen sections overnight at room temperature with polyclonal anti-fibrillin-1 antibody (Sima Aldrich) diluted 1 / 200 in 0.3% PBS-BSA and revealed with AlexaFluor AF488 (Lifetechnologies). Nuclei were counterstained with propidium iodide. Immunostaining was assessed by microscopy and semiquantified by image analysis.

[0180] The results obtained show that treatment with the placebo formulation (P1) or with the formulations containing only one of the two hyaluronic acids used according to the invention (P2 and P3) does not result in a significant (or noticeable) difference in the expression of fibrillin-1 at day 7.

[0181] In contrast, and surprisingly, the combination according to the invention of a low molecular weight hyaluronic acid such as "Bashyal" with a high molecular weight cross-linked hyaluronic acid such as "Hyacross TL 200" (formulation P4) significantly increases the expression of fibrillin-1 at day 7 (+35%). Thus, the combination of active ingredients according to the invention can show a synergistic effect on the expression of fibrillin-1.

[0182] Thus, these results indicate that a combination of low molecular weight hyaluronic acid and high molecular weight cross-linked hyaluronic acid according to the present invention can be used to promote skin firmness and / or elasticity.

[0183] Example 5: Cosmetic formulation according to the invention The compositions are prepared according to the conventional methods used in the cosmetic (or cosmetic) field.

[0184] Facial Plumper [Table 9]

[0185] Facial plumpers are moisturizing and smoothing treatments for the face, ideally intended for application in the morning and / or evening. When applied to the skin of the face and / or neck, especially around wrinkles and fine lines, they provide a rapid smoothing effect, reducing roughness and smoothing microrelief of the skin. Skin appears visibly smoother, brighter and younger.

[0186] Lip Plumper [Table 10]

[0187] Lip plumpers are moisturizing and plumping treatments for the lips. After application to the lips, fine lines are reduced and the lips appear fuller and plumper. The smoothing effect is immediate.

Claims

1. A cosmetic composition comprising, in a physiologically acceptable medium, a combination of at least one high molecular weight cross-linked hyaluronic acid or its salt having a molecular weight of 2000 kDa or more and a low molecular weight non-cross-linked hyaluronic acid or its salt having a molecular weight of 300 kDa or less.

2. The cosmetic composition according to claim 1, wherein the high molecular weight cross-linked hyaluronic acid has a molecular weight of 3000 kDa or more.

3. The cosmetic composition according to claim 1, wherein the low molecular weight non-crosslinked hyaluronic acid has an average molecular weight of 200 kDa or less.

4. 2. The cosmetic composition according to claim 1, wherein the high molecular weight cross-linked hyaluronic acid has the INCI name sodium hyaluronic acid crosspolymer.

5. 2. The cosmetic composition according to claim 1, wherein the low molecular weight non-crosslinked hyaluronic acid is selected from products having the INCI names sodium hyaluronate and hyaluronic acid.

6. 2. The cosmetic composition according to claim 1, characterized in that the high molecular weight cross-linked hyaluronic acid has a cross-linking of 0.001% to 5%, preferably 0.1% to 1%, preferably 0.1% to 0.6%.

7. The cosmetic composition according to claim 1, wherein the high molecular weight cross-linked hyaluronic acid and the low molecular weight non-cross-linked hyaluronic acid are each present in the composition in an amount ranging from 0.001 to 10% by weight, preferably from 0.005 to 5% by weight, more preferably from 0.01 to 1% by weight, based on the total weight of the composition.

8. 10. The cosmetic composition of claim 1, further comprising at least one cosmetic adjuvant selected from the group consisting of antioxidants, emollients, moisturizers, anti-aging agents, fragrances, and mixtures thereof.

9. 2. A cosmetic composition according to claim 1, characterized in that it contains less than 5% fillers, in particular less than 2% fillers, preferably less than 1% fillers, or is devoid of fillers.

10. 2. Cosmetic composition according to claim 1, characterized in that it is in the form of a topical composition for the skin and / or lips, in particular in the form of a cream, an oil-in-water or water-in-oil emulsion or multiple emulsion, a suspension, a gel, a milk, a lotion, a serum, a mask or a lip balm.

11. A cosmetic method for caring for keratinous materials, in particular the skin and / or lips, comprising topically applying to said keratinous materials at least one layer of a composition according to any one of claims 1 to 10.

12. 12. A cosmetic method according to claim 11, characterized in that it is intended to promote moisturizing of keratinous substances, in particular of the skin and / or lips, and / or to promote a rapid smoothing effect of keratinous substances, and / or to increase the firmness and / or elasticity and / or density and / or volume of keratinous substances, thereby preventing and / or reducing the signs of skin ageing, in particular the loss of firmness and / or elasticity and / or density and / or volume of the skin and / or lips, and / or the appearance of wrinkles and / or vertical lip lines, in particular at the lip contour.

13. 13. A cosmetic method according to claim 12, characterized in that the composition is applied to a healthy subject showing signs of skin and / or lip aging, in particular loss of firmness and / or elasticity and / or density and / or volume of the skin and / or lips, and / or wrinkles in the skin and / or lip contour, and / or thin lips and / or lips with vertical wrinkles.

14. Cosmetic use of a combination of active ingredients comprising at least one cross-linked hyaluronic acid or one of its salts having a high molecular weight, with a molecular weight of 2000 kDa or more, preferably 3000 kDa or more, and a low molecular weight non-cross-linked hyaluronic acid or one of its salts having a molecular weight of 300 kDa or less, for providing a rapid smoothing effect to keratinous materials, particularly for the skin and / or lips.