FR3148146A1 - COSMETIC COMPOSITION AND ITS USE - Google Patents

Abstract

COSMETIC COMPOSITION FOR SKIN CARE The present invention relates to a cosmetic composition comprising: (i) at least one acetylneuraminic acid; and (ii) at least one cordyceps militaris ferment extract. The present invention also relates to the use of the cosmetic composition and to a non-therapeutic method for caring for keratinous materials. Figure for abstract: none

Description

COSMETIC COMPOSITION FOR SKIN CARE

The present invention relates to a cosmetic composition. The present invention also relates to the use of the cosmetic composition and to a non-therapeutic method for caring for keratinous materials.

STATE OF THE ART

Human skin is made up of three compartments, namely a superficial compartment, which is the epidermis, the dermis and a deep compartment, which is the hypodermis.

The dermis is mainly composed of fibroblasts and an extracellular matrix (ECM). This extracellular matrix is composed of various macromolecules responsible for the mechanical resistance of the skin, its flexibility, tone and elasticity, as well as physiologically important functions (hydration, thermoregulation and regulation of skin permeability). These macromolecules include, in particular, collagens, elastin and glycoconjugates (glycoproteins and proteoglycans).

Collagens make up 70% of the proteins in the ECM. Naturally, collagens are constantly renewed, but this renewal decreases with age, leading to thinning of the dermis. The loss of collagen leads to skin wrinkles and a lack of firmness.

It is also known that prolonged exposure to ultraviolet radiation, particularly type A and B radiation, has the effect of stimulating the expression of collagenases, in particular MMP-1 (also called matrix metalloproteinase 1 or interstitial collagenase), constituting one of the components of photoinduced or non-photoinduced skin aging.

A wide variety of cosmetic products have been used to care for the skin, for example, to resist skin aging. However, some products are not effective enough.

Thus, there is always a need to formulate a skin care composition, which can effectively resist skin aging.

An object of the present invention is therefore to develop a skin care composition, which can effectively resist skin aging.

Another object of the present invention is to provide a cosmetic skin care process.

Inventors have now discovered that it is possible to formulate skin care compositions, which can effectively resist skin aging.

Accordingly, in a first aspect, the present invention provides a cosmetic composition comprising:

(i) at least one acetylneuraminic acid; and

(ii) at least one extract of cordyceps militaris ferment.

The inventors found that the composition of the present invention can improve the content of collagen I and inhibit the production of MMP-1, and effectively resist skin aging.

In a second aspect, the present invention provides the use of the composition of the present invention for the anti-aging of keratinous materials.

In a third aspect, the present invention provides a non-therapeutic method of caring for keratinous materials, comprising applying the composition according to the first aspect of the present invention to the keratinous materials.

Other subjects and features, aspects and advantages of the invention will become even more apparent from the following description and examples.

DETAILED DESCRIPTION OF THE INVENTION

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by a person skilled in the art in the field to which the present invention pertains. Where the definition of a term in the present invention conflicts with the meaning commonly understood by a person skilled in the art in the field to which the present invention pertains, the definition described in the present invention shall apply.

In the following and unless otherwise indicated, the limits of a range of values are included in this range, in particular in the expressions "between...and..." and "ranging from... to..".

Furthermore, the expression "at least one" used in the present description is equivalent to the expression "one or more".

Throughout this application, the term "comprising" should be construed to encompass all of the specifically mentioned features as well as optional, additional, unspecified features. As used herein, use of the term "comprising" also discloses the embodiment in which no features other than the specifically mentioned features are present (i.e., "consisting of").

Unless otherwise specified, all numerical values expressing an amount of ingredients and the like that are used in the description and claims are to be understood as being modified by the term "approximately". Accordingly, unless otherwise specified, the numerical values and parameters described herein are approximate values that may be changed depending on the desired purpose, if necessary.

For the purposes of the present invention, the term "keratinous materials" is intended to cover human skin and mucous membranes such as the lips. Facial skin is particularly considered according to the present invention.

In the present invention, all percentages refer, unless otherwise specified, to a percentage by weight.

1. au moins un acide acétylneuraminique ; et

1. au moins un extrait de ferment de cordyceps militaris.

According to the first aspect, a composition of the present invention comprises:

1. at least one acetylneuraminic acid; and

1. at least one extract of cordyceps militaris ferment.

Acetylneuraminic acid

According to the first aspect, the composition of the present invention comprises at least one acetylneuraminic acid.

Preferably, the acetylneuraminic acid is chosen from N-glycolylneuraminic acid (NGNA), N-acetylneuraminic acid (NANA), 5-N-acetyl-4-O-acetylneuraminic acid, 5-N-acetyl-7-O-acetylneuraminic acid, 5-N-acetyl-8-O-acetylneuraminic acid, 5-N-acetyl-9-O-acetylneuraminic acid, 5-N-acetyl-4,9-di-O-acetylneuraminic acid, 5-N-acetyl-7,9-di-O-acetylneuraminic acid, 5-N-acetyl-8,9-di-O-acetylneuraminic acid, 5-N-acetyl-7,8,9-tri-O-acetylneuraminic acid, 5-N-acetyl-9-O-L-lactyl-acetyl-neuraminic acid, 5-N-acetyl-4-O-acetyl-9-O-lactyl-acetyl-neuraminic acid, 5-N-acetyl-8-O-methyl-neuraminic acid, 5-N-acetyl-9-O-acetyl-8-O-methyl-neuraminic acid, 5-N-acetyl-8-O-sulpho-neuraminic acid, 5-N-acetyl-9-O-phosphoro-neuraminic acid, 5-N-acetyl-2-deoxy-2,3-didehydro-neuraminic acid, 5-N-acetyl-9-O-acetyl-2-deoxy-2,3-didehydro-neuraminic acid, 5-N-acetyl-2-deoxy-2,3-didehydro-9-O-lactyl-neuraminic acid, 5-N-acetyl-2,7-anhydro-neuraminic acid, 4-O-acetyl-5-N-glycolyl-neuraminic acid, 7-O-acetyl-5-N-glycolyl-neuraminic acid, 8-O-acetyl-5-N-glycolyl-neuraminic acid, 9-O-acetyl-5-N-glycolyl-neuraminic acid, 7,9-Di-O-acetyl-5-N-glycolyl-neuraminic acid, 8,9-Di-O-acetyl-5-N-glycolyl-neuraminic acid, 7,8,9-Tri-O-acetyl-5-N-glycolyl-neuraminic acid, 5-N-glycolyl-9-O-lactyl-neuraminic acid, 5-N-glycolyl-8-O-methyl-neuraminic acid, 9-O-Acetyl-5-N-glycolyl-8-O-methyl-neuraminic acid, 7,9-di-O-Acetyl-5-N-glycolyl-8-O-methyl-neuraminic acid, 5-N-glycolyl-8-O-sulphoneuraminic acid, N-(O-acetyl)glycolylneuraminic acid, N-(O-methyl)glycolylneuraminic acid, 2-deoxy-2,3-didehydro-5-N-glycolyl-neuraminic acid, 9-O-acetyl-2-deoxy-2,3-didehydro-5-N-glycolyl-neuraminic acid, 2-deoxy-2,3-didehydro-5-N-glycolyl-9-O-lactyl-neuraminic acid, 2-deoxy-2,3-didehydro-5-N-glycolyl-8-O-methyl-neuraminic acid, 2,7-anhydro-5-N-glycolyl-neuraminic acid, 2,7-anhydro-5-N-glycolyl-8-O-methyl-neuraminic acid, and combinations thereof.

More preferably, the acetylneuraminic acid is selected from N-glycolylneuraminic acid (NGNA), N-acetylneuraminic acid (NANA), 5-N-acetyl-4-O-acetylneuraminic acid, 5-N-acetyl-7-O-acetylneuraminic acid, 5-N-acetyl-8-O-acetylneuraminic acid, 5-N-acetyl-9-O-acetylneuraminic acid, 5-N-acetyl-4,9-di-O-acetylneuraminic acid, 5-N-acetyl-7,9-di-O-acetylneuraminic acid, 5-N-acetyl-8,9-di-O-acetylneuraminic acid, 5-N-acetyl-7,8,9-tri-O-acetylneuraminic acid, 5-N-acetyl-8-O-methyl-neuraminic acid, 5-N-acetyl-9-O-acetyl-8-O-methyl-neuraminic acid, 4-O-acetyl-5-N-glycolyl-neuraminic acid, 7-O-acetyl-5-N-glycolyl-neuraminic acid, 8-O-acetyl-5-N-glycolyl-neuraminic acid, 9-O-acetyl-5-N-glycolyl-neuraminic acid, 7,9-Di-O-acetyl-5-N-glycolyl-neuraminic acid, 8,9-Di-O-acetyl-5-N-glycolyl-neuraminic acid, 7,8,9-Tri-O-acetyl-5-N-glycolyl-neuraminic acid, 5-N-glycolyl-8-O-methyl-neuraminic acid, 9-O-acetyl-5-N-glycolyl-8-O-methyl-neuraminic acid, 7,9-di-O-acetyl-5-N-glycolyl-8-O-methyl-neuraminic acid, N-(O-acetyl)glycolyl-neuraminic acid, N-(O-methyl)glycolyl-neuraminic acid, and combinations thereof.

Even more preferably, the acetylneuraminic acid is selected from N-glycolylneuraminic acid (NGNA), N-acetylneuraminic acid (NANA), N-(O-acetyl)glycolylneuraminic acid, N-(O-methyl)glycolylneuraminic acid and combinations thereof.

In certain preferred embodiments, the composition of the present invention comprises N-acetylneuraminic acid (NANA).

Advantageously, acetylneuraminic acid is present in the composition of the present invention in an amount ranging from 0.001% by weight to 1.0% by weight, preferably from 0.005% by weight to 0.5% by weight, more preferably from 0.01% by weight to 0.3% by weight, relative to the total weight of the composition.

Cordyceps militaris ferment extract

According to the first aspect, the composition of the present invention comprises at least one cordyceps militaris ferment extract.

Preferably, the cordyceps militaris ferment extract is a lactococcus ferment extract based on cordyceps militaris.

Cordyceps militaris is the type species of Ascomycota, Hypocreas, Ergotaceae and Cordyceps. Cordyceps militaris cultivated by a living pupa is generally called cordyceps militaris. The main active ingredients of cordyceps militaris are cordycepin, cordycepic acid and cordyceps polysaccharide. Cordycepin is also known as 3-deoxyadenosine.

A fermentation extract of cordyceps militaris can be obtained as follows: lactobacilli are fermented and cultured in a fermentation medium using cordyceps militaris as a nitrogen source.

In particular, cordyceps militaris is the only source of nitrogen.

For more details on the production of cordyceps militaris ferment extract, please refer to CN111808901A.

As an example of commercial products of cordyceps militaris ferment extract, we can cite that sold under the name BIOYOUTH TM-CM® by the company BLOOMAGE BIOTECHNOLOGY.

Advantageously, the cordyceps militaris ferment extract is present in the composition of the present invention in an amount of dry matter ranging from 0.001% by weight to 1% by weight, preferably from 0.005% by weight to 0.5% by weight, more preferably from 0.01% by weight to 0.3% by weight, relative to the total weight of the composition.

Advantageously, the weight ratio between the at least one acetylneuraminic acid and the at least one cordyceps militaris ferment extract ranges from 1:10 to 2:1, preferably from 1:5 to 1:1.

Compound C-Glycoside

Advantageously, the composition of the present invention comprises at least one C-glycoside compound.

Preferably, the C-glycoside is chosen from the compounds of formula (I):
(I)

• R représente un radical alkyle saturé en C1 à C10, en particulier en C1 à C4 qui peut facultativement être substitué par au moins un radical choisi parmi OH, COOH ou COOR''2, R''2 étant un radical alkyle saturé en C1-C4,
• S représente un monosaccharide ou un polysaccharide comprenant jusqu’à 20 motifs sucre, en particulier jusqu’à 6 motifs sucre, sous forme de pyranose et/ou de furanose et des séries L et/ou D, ledit monosaccharide ou polysaccharide pouvant être substitué par un groupe hydroxyle qui est nécessairement libre et facultativement un ou plusieurs groupes fonctionnels amine facultativement protégés, et
• X représente un radical choisi dans les groupes -CO-, -CH(OH)-, -CH(NH₂)-, -CH(NHCH₂CH₂CH₂OH)-, -CH(NHPh)- et –CH(CH₃)- et en particulier un radical –CO-, -CH(OH)- ou –CH(NH₂)- et plus particulièrement un radical –CH(OH)-,

in which:

• R represents a saturated C1 to C10, in particular C1 to C4, alkyl radical which may optionally be substituted by at least one radical chosen from OH, COOH or COOR''2, R''2 being a saturated C1-C4 alkyl radical,
• S represents a monosaccharide or polysaccharide comprising up to 20 sugar units, in particular up to 6 sugar units, in the form of pyranose and/or furanose and of the L and/or D series, said monosaccharide or polysaccharide possibly being substituted by a hydroxyl group which is necessarily free and optionally one or more optionally protected amine functional groups, and
• X represents a radical chosen from the groups -CO-, -CH(OH)-, -CH(NH ₂ )-, -CH(NHCH ₂ CH ₂ CH ₂ OH)-, -CH(NHPh)- and –CH(CH ₃ )- and in particular a radical –CO-, -CH(OH)- or –CH(NH ₂ )- and more particularly a radical –CH(OH)-,

the S-CH ₂ -X bond represents a bond of C-anomeric nature, which can be α or β,

as well as their physiologically acceptable salts, their solvates, such as hydrates and their optical and geometric isomers.

The C-glycosides used for implementing the invention are in particular those for which R denotes a saturated linear alkyl radical in C ₁ to C ₆ , in particular in C ₁ to C ₄ , preferentially in C ₁ to C ₂ and more preferentially, a methyl radical.

Among the alkyl groups suitable for implementing the invention, mention may be made in particular of methyl, ethyl, isopropyl, n-propyl, n-butyl, t-butyl, isobutyl, sec-butyl, pentyl, n-hexyl, cyclopropyl, cyclopentyl or cyclohexyl groups.

According to one embodiment of the invention, it is possible to use a C-glycoside corresponding to formula (I) for which S can represent a monosaccharide or a polysaccharide comprising up to 6 sugar units, in the form of pyranose and/or furanose and of the L and/or D series, said monosaccharide or polysaccharide having at least one necessarily free hydroxyl functional group and/or optionally one or more necessarily protected amine functional groups, X and R moreover retaining all the definitions above.

Advantageously, a monosaccharide of the invention may be chosen from D-glucose, D-galactose, D-mannose, D-xylose, D-lyxose or L-fucose, L-arabinose, L-rhamnose, D-glucuronic acid, D-galacturonic acid, D-iduronic acid, N-acetyl-D-glucosamine or N-acetyl-D-galactosamine and advantageously denotes D-glucose, D-xylose, N-acetyl-D-glucosamine or L-fucose and in particular D-xylose.

More particularly, a polysaccharide of the invention comprising up to 6 sugar units may be chosen from D-maltose, D-lactose, D-cellobiose, D-maltotriose, a disaccharide combining a uronic acid chosen from D-iduronic acid or D-glucuronic acid with a hexosamine chosen from D-galactosamine, D-glucosamine, N-acetyl-D-galactosamine or N-acetyl-D-glucosamine, an oligosaccharide comprising at least one xylose which may advantageously be chosen from xylobiose, methyl-β-xylobioside, xylotriose, xylotetraose, xylopentaose and xylohexaose, and in particular xylobiose, which is composed of two xylose molecules linked via a 1-4 bond.

More particularly, S may represent a monosaccharide chosen from D-glucose, D-xylose, L-fucose, D-galactose or D-maltose and in particular D-xylose.

• R désigne un radical alkyle linéaire non substitué en C₁-C₄, en particulier en C₁-C₂, notamment un radical méthyle ;
• S représente un monosaccharide tel que décrit ci-dessus et choisi en particulier parmi D-glucose, D-xylose, N-acétyl-D-glucosamine ou L-fucose, et en particulier D-xylose ;
• X représente un groupe choisi parmi -CO-, -CH(OH)- ou -CH(NH₂) et, préférentiellement un groupe -CH(OH)-.

Preferably, a C-glycoside of formula (I) is used for which:

• R denotes an unsubstituted linear _C1 - _C4 , in particular _C1 - _C2 , alkyl radical, in particular a methyl radical;
• S represents a monosaccharide as described above and chosen in particular from D-glucose, D-xylose, N-acetyl-D-glucosamine or L-fucose, and in particular D-xylose;
• X represents a group chosen from -CO-, -CH(OH)- or -CH(NH ₂ ) and, preferably a -CH(OH)- group.

Acceptable salts of the compounds described herein include conventional non-toxic salts of said compounds, such as those formed from organic or inorganic acids. Examples include salts of inorganic acids such as sulfuric acid, hydrochloric acid. Also included are salts of organic acids, which may comprise one or more carboxylic, sulfonic or phosphonic acid groups. Particular examples include propionic acid, acetic acid, terephthalic acid, citric acid and tartaric acid.

When the compound of formula (I) comprises an acidic group, the neutralization of the acidic group(s) may be carried out with an inorganic base, such as LiOH, NaOH, KOH, Ca(OH) ₂ , NH ₄ OH, Mg(OH) ₂ or Zn(OH) ₂ , or with an organic base, such as a primary, secondary or tertiary alkylamine, for example triethylamine or butylamine. This primary, secondary or tertiary alkylamine may comprise one or more nitrogen and/or oxygen atoms and may thus comprise, for example, one or more alcohol functional groups; in particular, 2-amino-2-methylpropanol, triethanolamine, 2-(dimethylamino)propanol or 2-amino-2-(hydroxymethyl)-1,3-propanediol may be mentioned. Lysine or 3-(dimethylamino)propylamine may also be mentioned.

Solvates which are acceptable for the compounds described herein include conventional solvates, such as those formed during the final stage of preparation of said compounds due to the presence of solvents. Examples include solvates due to the presence of water or linear or branched alcohols, such as ethanol or isopropanol.

Of course, according to the invention, a C-glycoside corresponding to formula (I) can be used alone or in a mixture with other C-glycosides and in any proportion.

A C-glycoside which is suitable for the invention can in particular be obtained by the synthesis method described in WO 02/051828.

In particular, as a non-limiting illustration of the C-glycoside compounds which are particularly suitable for the invention, the following compounds may be cited:

- C-β-D-xylopyranoside-n-propane-2-one,

- C-α-D-xylopyranoside-n-propan-2-one,

- C-β-D-xylopyranoside-2-hydroxypropane,

- C-α- D-xylopyranoside-2-hydroxypropane,

- 1-(C-β-D-fucopyranoside)propan-2-one,

- 1-(C-α-D-fucopyranoside)propan-2-one,

- 1-(C-β-L-fucopyranoside)propan-2-one,

- 1-(C-α-L-fucopyranoside)propan-2-one,

- 1-(C-β-D-fucopyranoside)-2-hydroxypropane,

- 1-(C-α-D-fucopyranoside)-2-hydroxypropane,

- 1-(C-β-L-fucopyranoside)-2-hydroxypropane,

- 1-(C-α-L-fucopyranoside)-2-hydroxypropane,

- 1-(C-β-D-glucopyranosyl)-2-hydroxypropane,

- 1-(C-α-D-glucopyranosyl)-2-hydroxypropane,

- 1-(C-β-D-galactopyranosyl)-2-hydroxypropane,

- 1-(C-α-D-galactopyranosyl)-2-hydroxypropane,

- 1-(C-β-D-fucofuranosyl)propan-2-one,

- 1-(C-α-D-fucofuranosyl)propan-2-one,

- 1-(C-β-L-fucofuranosyl)propan-2-one,

- 1-(C-α-L-fucofuranosyl)propan-2-one,

- C-β-D-maltopyranoside-n-propane-2-one,

- C-α-D-maltopyranoside-n-propan-2-one,

- C-β-D-maltopyranoside-2-hydroxypropane,

- C-α-D-maltopyranoside-2-hydroxypropane, their isomers and their mixtures.

According to one embodiment, C-β-D-xylopyranoside-2-hydroxypropane or C-α-D-xylopyranoside-2-hydroxypropane and better still C-β-D-xylopyranoside-2-hydroxypropane can advantageously be used for the preparation of a composition according to the invention.

In a specific embodiment, the C-glycoside may be C-β-D-xylopyranoside-2-hydroxypropane (or hydroxypropyl tetrahydropyrantriol) provided as a solution containing 35% by weight of active material in water and propylene glycol.

If present, advantageously, the C-glycoside is present in the composition of the present invention in an amount ranging from 0.01% to 15% by weight, preferably from 0.05% to 10% by weight, more preferably from 0.1% to 8% by weight, relative to the total weight of the composition.

If present, advantageously, the ratio between the total weight of at least one acetylneuraminic acid and the at least one cordyceps militaris ferment extract and the weight of the C-glycoside ranges from 1:3 to 1:40, preferably from 1:10 to 1:35.

Aqueous phase

The composition of the present invention may comprise an aqueous phase.

Said aqueous phase comprises water.

Preferably, the composition according to the present invention comprises water.

Advantageously, water is present in the composition of the present invention in an amount ranging from 30% by weight to 98% by weight, preferably from 40% by weight to 90% by weight, more preferably from 50% by weight to 80% by weight, relative to the total weight of the composition.

Preferably, the aqueous phase comprises an organic solvent miscible with water (at room temperature 25°C) chosen from monoalcohols, glycols and polyols having from 2 to 20 carbon atoms, such as octyldodecanol, glycerin, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, dipropylene glycol, diethylene glycol; and mixtures thereof, so as to provide a hydration effect.

If present, advantageously, the water-miscible organic solvent chosen from monoalcohols, glycols and polyols is present in the composition in an amount ranging from 0.5% by weight to 30% by weight, preferably from 5% by weight to 20% by weight, relative to the total weight of the composition.

Preferably, the aqueous phase of the composition of the present invention comprises water and glycerin.

Oily phase

The composition of the present invention may comprise an oily phase.

The oil phase contains at least one oil. It may also contain other fatty substances.

Preferably, the composition comprises at least one oil.

The term "oil" means a non-aqueous, water-immiscible compound that is liquid at room temperature (20°C) and atmospheric pressure (760 mmHg).

Oils can be volatile or non-volatile.

The term "non-volatile" refers to an oil whose vapor pressure at room temperature and atmospheric pressure is non-zero and is less than 10-3 mmHg (0.13 Pa).

For the purposes of the invention, the expression “volatile oil” designates any oil which is capable of evaporating on contact with the skin in less than one hour, at room temperature and atmospheric pressure.

The oil phase may include hydrocarbon-based oils, silicone oils, or mixtures thereof.

They can be of animal, vegetable, mineral or synthetic origin.

For the purposes of the present invention, the expression “silicone oil” designates an oil comprising at least one silicon atom and in particular at least one Si-O group.

The term "hydrocarbon oil" means an oil containing primarily hydrogen and carbon atoms.

The oils may optionally comprise oxygen, nitrogen, sulfur and/or phosphorus atoms, for example in the form of hydroxyl or acid radicals.

If present, advantageously, the oily phase is present in the composition of the present invention in an amount ranging from 0.1% by weight to 40% by weight, preferably from 10% by weight to 25% by weight, relative to the total weight of the composition of the present invention.

Additional cosmetic active ingredients

The composition of the present invention may comprise an additional cosmetic active ingredient in addition to the cosmetic active ingredients as defined above.

Examples of cosmetic active ingredients include moisturizing agents; vitamins such as vitamin A (retinol), vitamin E (tocopherol), vitamin C (ascorbic acid), vitamin B5 (panthenol) and derivatives of said vitamins (in particular esters) and mixtures thereof; lightening agents; firming agents; exfoliating agents; moisturizing agents (HA); repairing and calming agents; other anti-aging agents; agents acting on microcirculation; sebum regulating agents; anti-acne agents; UV filters; agents acting on pigmentation and mixtures thereof.

It is easy for the person skilled in the art to adjust the amount of the additional cosmetic active ingredient depending on the end use of the composition according to the present invention.

Additional adjuvants or additives

The composition of the present invention may comprise conventional cosmetic adjuvants or additives, for example, fragrances, chelating agents, preservatives, surfactants, thickeners, pH regulators and mixtures thereof.

The person skilled in the art can choose the amount of the additional adjuvants or additives so as not to negatively impact the end use of the composition according to the present invention.

According to a particularly preferred embodiment, the present invention provides a cosmetic composition, comprising, relative to the total weight of the composition:

(i) from 0.01% by weight to 0.3% by weight of at least one acetylneuraminic acid selected from N-glycolylneuraminic acid (NGNA), N-acetylneuraminic acid (NANA), N-(O-acetyl)glycolylneuraminic acid, N-(O-methyl)glycolylneuraminic acid and combinations thereof; and

(ii) from 0.01% by weight to 0.3% by weight of a lactococcus ferment extract based on cordyceps militaris.

Dosage form and process

The composition of the present invention is in the form of an emulsion, a cream, a lotion, a mask or a hydrogel.

The composition of the present invention can be used for the care of keratinous materials.

According to the second aspect, the present invention provides the use of the composition of the present invention for the anti-aging of keratinous materials.

In particular, the present invention provides the use of the composition of the present invention for stimulating collagen production and/or inhibiting MMP-1 production.

According to the third aspect, the present invention provides a non-therapeutic method for caring for keratinous materials, comprising applying the composition according to the first aspect of the present invention to the keratinous materials.

In some embodiments, the present invention provides a non-therapeutic method of anti-aging keratinous materials, comprising applying the composition according to the first aspect of the present invention to the keratinous materials.

Keratinous materials are in particular the skin.

EXAMPLES

The following examples are given as non-limiting illustrations of the present invention.

The main raw materials used, trade names and their suppliers are listed in Table 1.

INCI name Trade name Supplier HYDROXYPROPYL TETRAHYDROPYRANTRIOL MEXORYL® SDL NEW ACETYLNEURAMINIC ACID SIALIC ACID WUHAN ZHONGKE OPTICS VALLEY GREEN LACTOCOCCUS FERMENT BIOYOUTH ^TM -CM BLOOMAGE BIOTECHNOLOGY

Example 1

The compositions of inventive formula 1 and comparative formulas 1-A and 1-B were prepared on the basis of the amounts given in Table 2. The amounts are given in % by weight of active ingredient relative to the total weight of the composition.

Active Inventive formula 1 Comparative formula 1-A Comparative formula 1-B % by weight % by weight % by weight ACETYLNEURAMINIC ACID 0.01 0.01 / LACTOCOCCUS FERMENT 0.01 / 0.01 Water Up to 100 Up to 100 Up to 100

The composition of the formula of the invention 1 represents the composition according to the present invention.

The composition of comparative formula 1-A does not include LACTOCOCCUS FERMENT.

The composition of comparative formula 1-B does not include ACETYLNEURAMINIC ACID.

Preparation process :

The compositions listed above were prepared as follows: dilution of each raw material in double distilled _H2O sterilized at room temperature and dissolution in water with stirring.

Assessment

The ELISA assay for type I collagen was performed as follows.

Normal human fibroblast cells were seeded into 6-well plates with a cell density of ^2X105 cells/well, under 5% _CO2 , 95% humidity, 37°C in a cell incubator (Thermo 150I) for overnight culture. When the cell density reached 40~60% confluence, the cell culture medium was replaced with fresh medium containing tested raw materials with different concentrations or combinations. The treated cells were placed in a cell incubator with 5% _CO2 , 95% humidity, 37°C for 24 hours.

Each test group consisted of three replicate cells. Cell culture supernatants were collected for ELISA assay of type I collagen (Cusabio). The no-treatment group was taken as blank control group (BC), the group treated with TGF-β1 (Peprotech) at 100 ng/ml was taken as positive control group (PC). The other three groups were treated with fresh medium containing compositions of the invention formula 1, comparative formulas 1-A and 1-B, respectively. The ELISA assay procedure was fully in accordance with the standard protocol illustrated in the test kit.

The relative improvement of collagen I content for each group was calculated according to the following formulas and the results were summarized in Table 3.

Amount of collagen I (mg/ml) of the _{test group}

Relative % collagen I content of the _{test group} = X 100%

Amount of collagen I (mg/ml) of the _{blank group}

Relative improvement in % collagen I content = relative % collagen I content - 100%

Properties Blank witness Positive witness Inventive formula 1 Comparative formula 1-A Comparative formula 1-B Relative improvement in collagen I content (%) 0 35.30 58.53 15.45 11.59

It can be seen from Table 3 that the composition of the invention formula 1 can significantly improve the content of collagen I, compared with the compositions of the comparative formulas 1-A and 1-B.

The relative improvement in the collagen I content of the inventive formula 1 is greater than the sum of that of the compositions of the comparative formulas 1-A and 1-B. Thus, it is demonstrated that the combination of LACTOCOCCUS FERMENT and ACETYLNEURAMINIC ACID improves the collagen I content.

Example 2

The compositions of inventive formula 2 and comparative formulas 2-A and 2-B were prepared on the basis of the amounts given in Table 4 following the protocol as described in Example 1. The amounts are given in % by weight of active ingredient relative to the total weight of the composition.

Active Formula of invention 2 Comparative formula 2-A Comparative formula 2-B % by weight % by weight % by weight ACETYLNEURAMINIC ACID 0.05 0.05 / LACTOCOCCUS FERMENT 0.05 / 0.05 Water Up to 100 Up to 100 Up to 100

The composition of the formula of the invention 2 represents the composition according to the present invention.

The composition of comparative formula 2-A does not include LACTOCOCCUS FERMENT.

The composition of comparative formula 2-B does not include ACETYLNEURAMINIC ACID.

The ELISA assay of type I collagen was performed according to the protocol described in Example 1, the relative improvement in collagen I content for each group was calculated and the results were summarized in Table 5.

Properties Blank witness Positive witness Formula of invention 2 Comparative formula 2-A Comparative formula 2-B Relative improvement in collagen I content (%) 0 35.30 65.05 35.57 24.42

It can be seen from Table 5 that the composition of inventive formula 2 can significantly improve the collagen I content, compared to the compositions of comparative formulas 2-A and 2-B.

The relative improvement in the collagen I content of the inventive formula 2 is greater than the sum of that of the compositions of the comparative formulas 2-A and 2-B. Thus, it is demonstrated that the combination of LACTOCOCCUS FERMENT and ACETYLNEURAMINIC ACID improves the collagen I content.

Example 3

The compositions of inventive formula 3 and comparative formulas 3-A and 3-B were prepared on the basis of the amounts given in Table 6 following the protocol as described in Example 1. The amounts are given in % by weight of active ingredient relative to the total weight of the composition.

Active Inventive formula 3 Comparative formula 3-A Comparative formula 3-B % by weight % by weight % by weight ACETYLNEURAMINIC ACID 0.15 0.15 / LACTOCOCCUS FERMENT 0.05 / 0.05 Water Up to 100 Up to 100 Up to 100

The composition of the formula of the invention 3 represents the composition according to the present invention.

The composition of the comparative formula 3-A does not include LACTOCOCCUS FERMENT.

The composition of comparative formula 3-B does not include ACETYLNEURAMINIC ACID.

The ELISA assay of type I collagen was performed according to the protocol described in Example 1, the relative improvement in collagen I content for each group was calculated and the results were summarized in Table 7.

Properties Blank witness Positive witness Inventive formula 3 Comparative formula 3-A Comparative formula 3-B Relative improvement in collagen I content (%) 0 35.30 264.67 194.10 36.74

It can be seen from Table 7 that the composition of the invention formula 3 can significantly improve the content of collagen I, compared with the compositions of the comparative formulas 3-A and 3-B.

The relative improvement in the collagen I content of the inventive formula 3 is greater than the sum of that of the compositions of the comparative formulas 3-A and 3-B. Thus, it is demonstrated that the combination of LACTOCOCCUS FERMENT and ACETYLNEURAMINIC ACID improves the collagen I content.

Example 4

The compositions of inventive formula 4 and comparative formulas 4-A and 4-B were prepared on the basis of the amounts given in Table 8 following the protocol as described in Example 1. The amounts are given in % by weight of active ingredient relative to the total weight of the composition.

Active Inventive formula 4 Comparative Formula 4-A Comparative Formula 4-B % by weight % by weight % by weight ACETYLNEURAMINIC ACID 0.01 / 0.01 LACTOCOCCUS FERMENT 0.01 0.01 / HYDROXYPROPYL TETRAHYDROPYRANTRIOL 0.44 0.44 / PROPYLENE GLYCOL 0.31 0.31 / Water Up to 100 Up to 100 Up to 100

The composition of the formula of the invention 4 represents the composition according to the present invention.

The composition of comparative formula 4-A does not include ACETYLNEURAMINIC ACID.

The composition of the comparative formula 4-B does not include LACTOCOCCUS FERMENT.

The ELISA assay of type I collagen was performed according to the protocol described in Example 1, the relative improvement in collagen I content for each group was calculated and the results were summarized in Table 9.

Properties Blank witness Positive witness Inventive formula 4 Comparative Formula 4-A Comparative Formula 4-B Relative improvement in collagen I content (%) 0 35.30 70.12 47.91 15.45

It can be seen from Table 9 that the composition of the invention formula 3 can significantly improve the content of collagen I, compared with the compositions of the comparative formulas 4-A and 4-B.

The relative improvement in the collagen I content of the inventive formula 4 is greater than the sum of that of the compositions of the comparative formulas 4-A and 4-B. Thus, it is demonstrated that the combination of LACTOCOCCUS FERMENT and ACETYLNEURAMINIC ACID improves the collagen I content.

It can also be seen from a comparison of the invention formula 1 and the invention formula 4 that the presence of hydroxypropyl tetrahydropyrantriol can significantly improve the collagen I content.

Example 5

The compositions of inventive formula 5 and comparative formulas 5-A and 5-B were prepared on the basis of the amounts given in Table 10 following the protocol as described in Example 1. The amounts are given in % by weight of active ingredient relative to the total weight of the composition.

Active Inventive formula 5 Comparative Formula 5-A Comparative Formula 5-B % by weight % by weight % by weight ACETYLNEURAMINIC ACID 0.10 0.10 / LACTOCOCCUS FERMENT 0.10 / 0.10 Water Up to 100 Up to 100 Up to 100

The composition of the formula of the invention 5 represents the composition according to the present invention.

The composition of the comparative formula 5-A does not include LACTOCOCCUS FERMENT.

The composition of the comparative formula 5-B does not include ACETYLNEURAMINIC ACID.

Assessment

The MMP-1 ELISA assay was performed as follows.

Cell seeding: Human skin fibroblasts were grown to 80% confluence, digested and suspended, and the cell density was adjusted to 30,000 cells/well using complete medium (DMEM with 10% SFV, Gibco, Lot: 2275120). Cells were inoculated onto a 24-well plate and incubated in a cell incubator (5% _CO2 , 95% humidity, 37 °C) for 24 hours.

Subject exposure : The original medium was removed and replaced with DMEM containing 1% FCS or DMEM 1% FCS containing different concentrations of samples, incubated in the incubator for 24 hours. The group treated with 0.1 μm dexamethasone (DT) was taken as the positive control group (PC). The group not treated with any composition was considered as the untreated group (NT). The other three groups were treated with fresh medium containing compositions of inventive formula 5, comparative formulas 5-A and 5-B, respectively.

UVA modeling : Before UVA irradiation, discard the medium, add 200μL/well of PBS. For plates requiring UVA irradiation, place them under an ultraviolet lamp, adjust the UVA irradiation intensity to 2.5 mW/ ^cm2 , irradiate at 6J/cm2 UVA (~40 min). For the control plate without UVA (blank control), place the plate on the area without UVA irradiation. After irradiation, the PBS was removed and replaced with DMEM containing 1% FCS or DMEM 1% FCS containing different concentrations of raw materials, plates were placed in the incubator for 48 hours. After incubation, the supernatant was collected into sterile Eppendorf tubes, centrifuged at 12,000 rpm for 5 min at low temperature, and stored at -80 °C.

The ELISA procedure fully followed the kit instructions (R&D, #DY901B, Lot: P288649).

The relative inhibition of MMP-1 content for each group was calculated according to the following formula and the results were summarized in Table 11.

Amount of MMP1(mg/ml) in _{test group/UVA}

Relative % MMP1 content of the _{test group/UVA} = X 100%

MMP1 quantity (mg/ml) of _NT/UVA

Relative inhibition of MMP1 content % _{of test group/UVA} = 100% - relative MMP1 content % of _group/UVA

Properties Blank witness Positive witness Inventive formula 5 Comparative Formula 5-A Comparative Formula 5-B Relative inhibition of MMP-1 content (%) 0 53.83 59.33 17.23 39.00

It can be seen from Table 11 that the composition of the inventive formula 5 can significantly inhibit the content of MMP-1, compared with the compositions of the comparative formulas 5-A and 5-B.

The relative improvement in the collagen I content of the inventive formula 5 is greater than the sum of that of the compositions of the comparative formulas 5-A and 5-B. Thus, it is demonstrated that the combination of LACTOCOCCUS FERMENT and ACETYLNEURAMINIC ACID inhibits the MMP-1 content.

In summary, the composition according to the present invention can improve the content of collagen I and inhibit the production of MMP-1, therefore can effectively resist skin aging.

Claims (10)

Cosmetic composition comprising:
(i) at least one acetylneuraminic acid; and
(ii) at least one extract of cordyceps militaris ferment. The composition of claim 1, wherein the acetylneuraminic acid is selected from N-glycolylneuraminic acid (NGNA), N-acetylneuraminic acid (NANA), 5-N-acetyl-4-O-acetylneuraminic acid, 5-N-acetyl-7-O-acetylneuraminic acid, 5-N-acetyl-8-O-acetylneuraminic acid, 5-N-acetyl-9-O-acetylneuraminic acid, 5-N-acetyl-4,9-di-O-acetylneuraminic acid, 5-N-acetyl-7,9-di-O-acetylneuraminic acid, 5-N-acetyl-8,9-di-O-acetylneuraminic acid, 5-N-acetyl-7,8,9-tri-O-acetylneuraminic acid, 5-N-acetyl-9-O-L-lactyl-acetyl-neuraminic acid, 5-N-acetyl-4-O-acetyl-9-O-lactyl-acetyl-neuraminic acid, 5-N-acetyl-8-O-methyl-neuraminic acid, 5-N-acetyl-9-O-acetyl-8-O-methyl-neuraminic acid, 5-N-acetyl-8-O-sulpho-neuraminic acid, 5-N-acetyl-9-O-phosphoro-neuraminic acid, 5-N-acetyl-2-deoxy-2,3-didehydro-neuraminic acid, 5-N-acetyl-9-O-acetyl-2-deoxy-2,3-didehydro-neuraminic acid, 5-N-acetyl-2-deoxy-2,3-didehydro-9-O-lactyl-neuraminic acid, 5-N-acetyl-2,7-anhydro-neuraminic acid, 4-O-acetyl-5-N-glycolyl-neuraminic acid, 7-O-acetyl-5-N-glycolyl-neuraminic acid, 8-O-acetyl-5-N-glycolyl-neuraminic acid, 9-O-acetyl-5-N-glycolyl-neuraminic acid, 7,9-Di-O-acetyl-5-N-glycolyl-neuraminic acid, 8,9-Di-O-acetyl-5-N-glycolyl-neuraminic acid, 7,8,9-Tri-O-acetyl-5-N-glycolyl-neuraminic acid, 5-N-glycolyl-9-O-lactyl-neuraminic acid, 5-N-glycolyl-8-O-methyl-neuraminic acid, 9-O-Acetyl-5-N-glycolyl-8-O-methyl-neuraminic acid, 7,9-di-O-acetyl-5-N-glycolyl-8-O-methyl-neuraminic acid, 5-N-glycolyl-8-O-sulphoneuraminic acid, N-(O-acetyl)glycolylneuraminic acid, N-(O-methyl)glycolylneuraminic acid, 2-deoxy-2,3-didehydro-5-N-glycolyl-neuraminic acid, 9-O-acetyl-2-deoxy-2,3-didehydro-5-N-glycolyl-neuraminic acid, 2-deoxy-2,3-didehydro-5-N-glycolyl-9-O-lactyl-neuraminic acid, 2-deoxy-2,3-didehydro-5-N-glycolyl-8-O-methyl-neuraminic acid, 2,7-anhydro-5-N-glycolyl-neuraminic acid, 2,7-anhydro-5-N-glycolyl-8-O-methyl-neuraminic acid, and combinations thereof. A composition according to any one of claims 1 to 2, wherein the cordyceps militaris ferment extract is a cordyceps militaris-based lactococcus ferment extract. Composition according to any one of claims 1 to 3, in which the weight ratio between the at least one acetylneuraminic acid and the at least one cordyceps militaris ferment extract ranges from 1:10 to 2:1, preferably from 1:5 to 1:1. A composition according to any one of claims 1 to 4, further comprising a C-glycoside. Composition according to claim 5, in which the C-glycoside is chosen from compounds of formula (I):
(I)
in which:
- R represents a saturated C ₁ to C ₁₀ alkyl radical, in particular C ₁ to C _{4 ,} which may optionally be substituted by at least one radical chosen from OH, COOH or COOR'' ₂ , R'' ₂ being a saturated C ₁ -C ₄ alkyl radical,
- S represents a monosaccharide or polysaccharide comprising up to 20 sugar units, in particular up to 6 sugar units, in the form of pyranose and/or furanose and of the L and/or D series, said monosaccharide or polysaccharide possibly being substituted by a hydroxyl group which is necessarily free and optionally one or more optionally protected amine functional groups, and
- X represents a radical chosen from the groups -CO-, -CH(OH)-, -CH(NH ₂ )-, -CH(NHCH ₂ CH ₂ CH ₂ OH)-, -CH(NHPh)- and –CH(CH ₃ )- and in particular a radical –CO-, -CH(OH)- or –CH(NH ₂ )- and more particularly a radical –CH(OH)-,
the S-CH ₂ -X bond represents a bond of C-anomeric nature, which can be α or β,
as well as their physiologically acceptable salts, their solvates, such as hydrates and their optical and geometric isomers. Composition according to claim 6, in which the C-glycoside is chosen from
- C-β-D-xylopyranoside-n-propane-2-one,
- C-α-D-xylopyranoside-n-propan-2-one,
- C-β-D-xylopyranoside-2-hydroxypropane,
- C-α- D-xylopyranoside-2-hydroxypropane,
- 1-(C-β-D-fucopyranoside)propan-2-one,
- 1-(C-α-D-fucopyranoside)propan-2-one,
- 1-(C-β-L-fucopyranoside)propan-2-one,
- 1-(C-α-L-fucopyranoside)propan-2-one,
- 1-(C-β-D-fucopyranoside)-2-hydroxypropane,
- 1-(C-α-D-fucopyranoside)-2-hydroxypropane,
- 1-(C-β-L-fucopyranoside)-2-hydroxypropane,
- 1-(C-α-L-fucopyranoside)-2-hydroxypropane,
- 1-(C-β-D-glucopyranosyl)-2-hydroxypropane,
- 1-(C-α-D-glucopyranosyl)-2-hydroxypropane,
- 1-(C-β-D-galactopyranosyl)-2-hydroxypropane,
- 1-(C-α-D-galactopyranosyl)-2-hydroxypropane,
- 1-(C-β-D-fucofuranosyl)propan-2-one,
- 1-(C-α-D-fucofuranosyl)propan-2-one,
- 1-(C-β-L-fucofuranosyl)propan-2-one,
- 1-(C-α-L-fucofuranosyl)propan-2-one,
- C-β-D-maltopyranoside-n-propane-2-one,
- C-α-D-maltopyranoside-n-propan-2-one,
- C-β-D-maltopyranoside-2-hydroxypropane,
- C-α-D-maltopyranoside-2-hydroxypropane,
their isomers and their mixtures. Composition according to claim 1, comprising, relative to the total weight of the composition:
(i) from 0.01% by weight to 0.3% by weight of at least one acetylneuraminic acid selected from N-glycolylneuraminic acid (NGNA), N-acetylneuraminic acid (NANA), N-(O-acetyl)glycolylneuraminic acid, N-(O-methyl)glycolylneuraminic acid and combinations thereof; and
(ii) from 0.01% by weight to 0.3% by weight of a lactococcus ferment extract based on cordyceps militaris. Use of the composition according to any one of claims 1 to 8 for the anti-aging of keratinous materials, in particular the skin. Non-therapeutic method for caring for keratinous materials, comprising the application of the composition according to any one of claims 1 to 8 to keratinous materials, in particular the skin.