FR3133750A1 - New compositions combining hemp derivatives and their use, particularly in cosmetics - Google Patents

Abstract

The present invention relates to new compositions combining hemp derivatives and their use in cosmetics, dermo-cosmetics, as well as their pharmaceutical use, particularly in dermatology, in particular for the treatment of irritation of sensitive skin and dysbiosis.

Description

New compositions combining hemp derivatives and their use, particularly in cosmetics FIELD OF INVENTION

The present invention relates to new compositions combining hemp derivatives and their use in cosmetics, dermo-cosmetics, as well as their pharmaceutical use, particularly in dermatology, in particular for the treatment of irritation of sensitive skin and dysbiosis.

STATE OF THE ART

Human skin constitutes a barrier against external attacks, in particular chemical, mechanical or infectious, and, as such, a certain number of defense reactions against environmental factors (climate, ultraviolet rays, tobacco, etc.) and/or xenobiotics, such as microorganisms, occur at its level. This property, called barrier function, is mainly provided by the most superficial layer of the epidermis, namely the stratum corneum, called stratus corneum .

The quality of the skin barrier and mucous membranes is affected daily following external attacks such as irritant agents (detergents, acids, bases, oxidants, reducers, concentrated solvents, toxic gases or fumes), mechanical stresses (friction, shocks, abrasion , tearing of the surface, projection of dust, particles, shaving or hair removal), or thermal or climatic imbalances (UV, cold, dryness) which may lead to skin irritation.

Generally speaking, skin disorders are more common in the most exposed areas of the body, namely the hands, feet, face, and scalp. They can occur in particular on areas subject to certain daily or frequently repeated hygiene procedures such as shaving, hair removal, detergency with toiletries or household products, the application of adhesives (dressings, patches, fixing prostheses), or in the case of sporting, professional or simply lifestyle-related actions and the use of clothing, tools or equipment generating localized friction. They can also be amplified by psychological stress.

Skin irritation is classically defined as a local inflammatory reaction. There is very sensitive skin prone to inflammation on a more or less chronic basis. The symptoms of sensitive skin are more or less diffuse and localized redness, itching, tightness and sometimes localized swelling. These feelings of discomfort can be due to external aggressions or internal factors. In all cases, they manifest in the form of micro-inflammation or revealed inflammation.

Vitamin D regulates many processes involved in skin homeostasis: the formation and maintenance of the epidermal barrier, hair growth, the innate immune system as well as aging.

Fructans, also called oligo-fructans, are known to act in a similar way to vitamin D on skin cells, in particular to stimulate the signaling pathways regulated by the vitamin D receptor in skin cells.

Fructans are also known for their prebiotic effects, that is to say that they are not metabolized by pathogenic bacteria, responsible for diseases in general and which are found in quantity in skin dysbiosis in particular.

Fructans are homopolymers of fructose linked to the fructosyl or glucosyl residue of a sucrose molecule. They are synthesized by plants or by microorganisms from sucrose. Fructans constitute, in the same way as starch, a carbon reserve for the body which accumulates them.

There are several categories of fructans depending on the type of bond present between the fructose units.

• Inulin, a fructan accumulated by plants of the Asteraceae family, consists of fructose residues linked by β(2→1) saccharide bonds.
• Levan-type fructans are produced by bacteria and consist of fructose residues linked by β(2→6) bonds.
• Mixed fructans which are a mixture of the first two having β(2→1) type bonds and β(2→6) type bonds.

Plants in the grass family (Poaceae) accumulate a type of fructan, graminans. These contain both types of bonds, which can represent 75 to 90% of the reserve carbohydrates of the vegetative organs.

Furthermore, non-psychotropic phyto-cannabinoids are effective for skin conditions such as inflammation, itching, pruritus.

By “phyto-cannabinoid” we mean a cannabinoid of plant origin.

Cannabidiol (CBD) or 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol, is the second most common phyto-cannabinoid abundant in hemp. Cannabidiol can be extracted from several varieties of hemp, including Cannabis sativa , indica and ruderalis . In particular, it can be extracted pure from genetically modified hemp plants or synthesized in the laboratory. A lipophilic substance, cannabidiol does not have a psychoactive effect. Its structure is presented below:

Chemical structure of cannabidiol

Cannabigerol (CBG) is another phyto-cannabinoid, present in low levels, around 1%, in hemp. Its structure is presented below.

Chemical structure of cannabigerol (CBG) TECHNICAL PROBLEM

There is a need to have effective active ingredients to reduce the disorders mentioned above, and in particular skin irritation. Indeed, numerous cosmetic compositions intended for the care of skin dysbiosis have been proposed to date, but none makes it possible to resolve this dilemma: to protect without irritating, to act on pathogenic bacteria only and to regulate the synthesis of vitamin D in the quantity necessary for the proper functioning of skin cells.

One of the aims of the invention is to propose compositions making it possible to treat and soothe irritated skin.

Another aim of the invention is to propose compositions making it possible to treat dysbiosis where we find lesions superinfected by pathogenic bacteria.

Another aim of the invention is to propose compositions capable of being used on healthy skin which is sensitive and/or reactive.

INVENTION

Surprisingly, the inventors discovered that the combination of an oligofructan and a phyto-cannabinoid turns out to present a synergy between these substances resulting in remarkable anti-irritant properties.

Indeed, surprisingly, the use on the skin of fructans makes it possible to restore the functionality of the vitamin D receptor in skin cells, and through this mechanism to stimulate the molecular network involved in the terminal differentiation of keratinocytes and promote the formation of the skin barrier.

The interests of the present discovery thus appear multiple by making it possible to limit skin irritation while benefiting from the positive biological effects of vitamin D without having to irritate the skin.

A first object of the present invention relates to an association comprising or consisting of a mixture of an oligofructan and at least one non-psychotropic phyto-cannabinoid.

For the purposes of the present invention, the fructans are chosen from plant extracts or fruits known to contain significant quantities of fructans, presented below:

SOURCES Fructan content (g/100g whole product) Artichoke 1.2-6.8 Jerusalem artichoke 12.2-20 Asparagus 0-3.0 Banana, common 0.0-0.7 Barley 0.5-1.5 Beet 0.4 Brussels sprouts 0.3 Melon, Cantaloupe 0.2 Chicory, root 0.4-20 Garlic 9.8-17.4 Grapefruit 0.2 Leek, whole 0.5-3 Honeydew melon 0.2 Nectarine 0.2 Onion powder 4.5 Onion, shallot 0.9-8.9 Onion, Spanish 0.1-1.8 Onion, white 1.1-7.5 White peach 0.4 Spinach, baby 0.1 Rye 0.5-1.5 Watermelon, seedless 0.3 Wheat 0.4-1.3 Zucchini zucchini 0.3

Thus, according to one embodiment of this first object, the invention relates to the association as described above in which the oligofructan is an extract of plants or fruits chosen from: artichoke, Jerusalem artichoke, asparagus, banana, barley, beetroot, Brussels sprouts, melon, cantaloupe melon, chicory, garlic, grapefruit, leek, nectarine, onion, shallot onion, Spanish onion, white onion, white peach, spinach, rye, watermelon, wheat and zucchini zucchini.

In a particularly preferred embodiment, said oligofructan is an extract of plants or fruits chosen from: rye, artichoke, asparagus and chicory.

For the purposes of the present invention, the oligofructan can also be chosen from the products obtained by bio-fermentation from chicory root inulin partially hydrolyzed by a specific endo-inulinase, such as fructo-oligosaccharide (FOS), raffinose (GGF), or xylo-oligosaccharides (XOS). Their chemical formulas are presented below:

Chemical structure of fructo-oligosaccharide (FOS)

Chemical structure of xylo-oligosaccharides (XOS)

For the purposes of the present invention, the oligofructan may be raffinose (GGF). Its structure is presented below:

Chemical structure of raffinose (GGF)

Thus, in one embodiment, the invention relates to the combination as described above in which the oligofructan is chosen from: fructo-oligosaccharide (FOS), xylo-oligosaccharides (XOS) and raffinose (GGF ).

For the purposes of the present invention, non-psychotropic phyto-cannabinoid means a derivative not exhibiting the known psychotropic properties of THC.

More Particularly, according to a particular embodiment, the non-psychotropic phyto-cannabinoid is chosen from cannabidiol or cannabigerol.

According to a particular embodiment, the cannabidiol or cannabigerol used is of natural origin and comes in particular from plant extracts of different varieties of hemp, in particular Cannabis sativa , indica or ruderalis .

According to a particular embodiment, the cannabidiol or cannabigerol used is isolated by methods known to those skilled in the art, for example including the collection of plant materials, extraction and purification.

According to a particular embodiment, the cannabidiol or cannabigerol used comes from hemp extracts containing less than 0.2% THC.

According to a particular embodiment, the cannabidiol or cannabigerol used comes from plants or extracts in accordance with the national laws in force.

According to a particular embodiment, the present invention relates to a combination comprising or consisting of a mixture of an oligofructan and at least one non-psychotropic phyto-cannabinoid, as defined above and more particularly of a fructo mixture. -oligosaccharide and cannabidiol.

According to a particular embodiment, the present invention relates to an association comprising or consisting of a mixture of an oligofructan and at least one non-psychotropic phyto-cannabinoid, as defined above and more particularly of a xylomixture. -oligosaccharide and cannabidiol.

According to a particular embodiment, the present invention relates to a combination comprising or consisting of a mixture of an oligofructan and at least one non-psychotropic phyto-cannabinoid, as defined above and more particularly of a raffinose mixture. and cannabidiol.

According to a particular embodiment, the present invention relates to a combination comprising or consisting of a mixture of an oligofructan and at least one non-psychotropic phyto-cannabinoid, as defined above and more particularly of a fructo mixture. -oligosaccharide and cannabigerol.

According to a particular embodiment, the present invention relates to an association comprising or consisting of a mixture of an oligofructan and at least one non-psychotropic phyto-cannabinoid, as defined above and more particularly of a xylomixture. -oligosaccharide and cannabigerol.

According to a particular embodiment, the present invention relates to a combination comprising or consisting of a mixture of an oligofructan and at least one non-psychotropic phyto-cannabinoid, as defined above and more particularly of a raffinose mixture. and cannabigerol.

In other words, in a particular embodiment, the present invention relates to the association as described above in which the association is chosen from the mixture:

• fructo-oligosaccharide and cannabidiol;
• xylo-oligosaccharide and cannabidiol;
• raffinose and cannabidiol;
• fructo-oligosaccharide and cannabigerol;
• xylo-oligosaccharide and cannabigerol; And
• raffinose and cannabigerol.

In a particular embodiment, the present invention relates to the association as described above in which the ratio between the oligofructan and the phyto-cannabinoid is between 30:0.1 and 1:10.

According to a particular embodiment, the present invention relates to an association as defined above, comprising at least one other substance having a soothing effect on the skin.

In a second subject , the invention relates to a cosmetic or dermo-cosmetic composition comprising the combination as defined above.

In other words, in this second subject, the invention relates to a cosmetic or dermo-cosmetic composition comprising or consisting of a mixture of an oligofructan and at least one non-psychotropic phyto-cannabinoid.

All the embodiments defined in the first object of the invention concerning said association apply in this second object.

By “cosmetic composition” or “dermo-cosmetics” is meant any composition for cosmetic purposes, in particular a composition which can be brought into contact with the superficial parts of the human body, the skin, in particular the epidermis, the mucous membranes and the scalp. .

For the purposes of the present invention, the term "cosmetic composition" or "dermo-cosmetic" means a non-pharmaceutical composition, that is to say one which does not require therapeutic treatment, that is to say intended for any healthy skin area.

The term “healthy skin” means an area of skin, to which the association or composition according to the invention called “non-pathological” by a dermatologist, that is to say not showing infection, is applied, of illness, or sores or injuries and/or other dermatoses.

Another aspect of this second object concerns a cosmetic composition, comprising an association as defined above, in a cosmetically acceptable medium.

In other words, in another aspect of this second subject, the invention relates to a cosmetic or dermo-cosmetic composition comprising or consisting of a mixture of an oligofructan and at least one non-psychotropic phyto-cannabinoid in a cosmetically acceptable medium.

By “a cosmetically acceptable medium”, within the meaning of the invention is meant a medium compatible with use in cosmetics.

In a particular embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition as described above in which the oligofructan is present in an amount of 0.01 to 30% by mass relative to the total mass of the composition.

In a particularly preferred embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition as described above in which the oligofructan is present at a rate of 0.1% by mass relative to the total mass of the composition.

In a particularly preferred embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition as described above in which the oligofructan is present at a rate of 10% by mass relative to the total mass of the composition.

In a particular embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition as described above in which the non-psychotropic phyto-cannabinoid is present at a rate of 0.1 to 10% by mass relative to the total mass of the composition.

In a particular embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition as described above in which the non-psychotropic phyto-cannabinoid is present at a rate of 5% by mass relative to the total mass of the composition.

In a particular embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition as described above in which the non-psychotropic phyto-cannabinoid is present at a rate of 0.5% by mass relative to the total mass of the composition. .

The term “from 0.01 to 30%” means the following ranges: from 0.01 to 0.025%; from 0.025 to 0.05%; from 0.05 to 0.1%; from 0.1 to 0.5%; from 0.5 to 1.0%; from 1.0 to 1.5%; from 1.5 to 2.0%; from 2.0 to 2.5%; from 2.5 to 3.0%; from 3.0 to 3.5%; from 3.5 to 4.0%; from 4.0 to 4.5%; from 4.5 to 5.0%; from 5% to 6%; from 6 to 7%; 7 to 8%; 8 to 9%; from 9 to 10%; from 10 to 15%; from 15 to 20%; from 20 to 25%; from 25 to 30%.

“From 0.1 to 10%” means the following ranges: from 0.01 to 0.025%; from 0.025 to 0.05%; from 0.05 to 0.1%; from 0.1 to 0.5%; from 0.5 to 1.0%; from 1.0 to 1.5%; from 1.5 to 2.0%; from 2.0 to 2.5%; from 2.5 to 3.0%; from 3.0 to 3.5%; from 3.5 to 4.0%; from 4.0 to 4.5%; from 4.5 to 5.0%; from 5.5 to 6%; from 6 to 6.5%; from 6.5 to 7%; from 7 to 7.5%; from 7.5 to 8%; from 8 to 8.5%; from 8.5 to 9%; from 9 to 9.5%; from 9.5 to 10%.

According to a particular embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition, comprising a combination as defined above, said composition comprising at least one other ingredient.

According to a particular embodiment, said ingredient is chosen in particular from agents derived from vitamin D such as 7-DHC (7-Dehydrocholesterol). 7-dehydrocholesterol is a natural precursor of vitamin D3 (cholecalciferol). In vitro testing indicates that 7-dehydrocholesterol may provide skin protection and repair benefits by targeting various natural skin markers. 7-DHC promotes skin cell differentiation and stimulates natural antimicrobial peptides in the skin, while providing all the benefits of vitamin D.

According to one embodiment, said cosmetic or dermo-cosmetic composition may also contain artificial tanning and/or browning agents for the skin (self-tanning agents), such as for example, tyrosine derivatives or dihydroxyacetone (DHA). ).

According to another particular embodiment, said ingredient is chosen in particular from moisturizing agents, chemical filters, sun filters in particular UVA filters, inorganic mineral sun filters, in particular Titanium dioxide, thermal waters, in particular water of Treignac®.

As examples of sun filters which can be associated with the composition of the present invention as defined above, we can cite all those appearing in cosmetic directive 76/768/EEC as amended, annex VII.

Among the “ chemical filters ” we can cite, for example:

• anthranilates, such as menthyl anthranilate,
• benzophenones, such as benzophenone-2 (oxybenzone), benzophenone-4 (Uvinul® MS40 (INCI: benzophenone-4))
• benzylidene camphors, such as 4-methylbenzylidene camphor (Eusolex® 6300 (INCI: Methylbenzylidene Camphor)),

• benzimidazoles, such as benzimidazilate (Neo Heliopan® AP (INCI: Disodium Phenyl Bidenzimidazole Tetrasulfonate)), or phenylbenzimidazole sulfonic acid (Eusolex® 232 (INCI: Phenylbenzimidazole Sulfonic Acid))

• benzotriazoles, such as methylene bis-benzotriazolyltetramethylbutylphenol (Tinosorb® M (INCI: Methylene Bis-Benzotriazolyl Tetramethylbutylphenol (nano)),
• cinnamates, such as ethocrylene (Uvinul® N35), octylmethoxycinnamate (Parsol® MCX (INCI: Ethylhexyl Methoxycinnamate), or octocrylene (Uvinul® 539 (INCI: Octocrylene)),
• dibenzoylmethanes, such as butyl methoxydibenzoylmethane (Parsol® 1789 (INCI: Butyl Methoxydibenzoylmethane)),
• imidazolines, such as ethylhexyl dimethoxybenzylidene dioxoimidazoline,
• PABAs, such as diethylhexylbutamido-triazone (Uvasorb® HEB (INCI: Diethylhexyl butamido triazone)), ethylhexyltriazone (Uvinul® T150 (INCI: Ethylhexyl Triazone), or ethyl PABA (benzocaine),
• salicylates, such as dipropylene glycol salicyclate, ethylhexyl salicylate, homosalate, or TEA salicylate,
• triazines, such as anisotriazine (Tinosorb® (INCI: Bis-Ethylhexyloxyphenol methoxyphenyl Triazine)),

or a mixture of these filters.

Among the “ inorganic filters ”, also called “mineral screens”, which can be associated with the formulation for topical use which is the subject of the present invention, we can cite titanium oxides such as TiO ₂ , zinc oxides such as ZnO, cerium oxide, zirconium oxide, yellow, red or black iron oxides, chromium oxides, or a mixture of these filters. These mineral screens may or may not be micronized, may or may not have undergone surface treatments and possibly be presented in the form of aqueous or oily pre-dispersions.

The composition of the present invention may also contain other adjuvants and excipients usual in the cosmetic fields.

Thus, in a particular embodiment, the cosmetic or dermo-cosmetic composition as defined above further comprises at least one adjuvant agent chosen from: fatty substances, organic solvents, ionic or non-ionic thickeners, softeners, antioxidants, opacifiers, stabilizers, emollients, silicones, α-hydroxy acids, anti-foaming agents, moisturizing agents, vitamins, preservatives, surfactants, fillers, sequestrants, polymers, propellants and alkalizing or acidifying agents, dyes.

For the purposes of the invention, fatty substances can consist of an oil or a wax or mixtures thereof, and they also include fatty acids, fatty alcohols and fatty acid esters. Fatty acid esters can be of plant origin (coconut, palm), or of synthetic origin and particularly esters of benzoic acid and/or neopentanoic acid (trimethylacetic).

The oils can be chosen from vegetable oils and in particular from oils: Moringa, calophyllum inophyllum, camelina, flax, chia, mineral or synthetic oils and in particular from vaseline oil, paraffin, polybutenes and isobutenes, silicone oils, volatile or not, isoparaffins, poly α olefins, fluorinated and perfluorinated oils. Likewise, the waxes can be chosen from fossil, vegetable, mineral or synthetic waxes known to those skilled in the art.

The thickeners can be chosen in particular from crosslinked polyacrylic acids, guar gums and modified or unmodified celluloses such as hydroxypropylated guar gum, methylhydroxyethylcellulose and hydroxy-propyl-methylcellulose.

Among the “moisturizing agents” we can cite, by way of example, sodium lactate, polyols, in particular glycerin, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, dipropylene glycol, diethylene glycol, mannitol and amino acids, caprylic/capric triglyceride, or a mixture of these agents.

As “antioxidants”, we can cite, for example, tocopherol (vitamin E) or ascorbic acid (vitamin C).

As “preservatives”, we can cite, for example, benzalkonium chloride, phenoxyethanol, or sorbic acid.

In a particular embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition as defined above, said composition being formulated for topical application.

More particularly, said cosmetic or dermo-cosmetic composition is formulated for topical application to the skin.

In a particular embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition as defined above, said composition being in the form of an aerosol, a simple or complex emulsion, a non-vesicular dispersion ionic, a cream, a gel, a gel cream, a lotion, an oil, a dispersion, a serum, a foam, a body milk or 'an anhydrous balm.

An emulsion according to the present invention may be an oil-in-water emulsion, or a water-in-oil emulsion. The fats and emulsifiers present in the emulsions according to the present invention are those usually used in cosmetics.

According to another particular embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition as defined above, said composition being in the form of a day cream, a night cream, a powder , a solid stick, a foam or a spray.

According to another particular embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition as defined above, said composition being in the form of a cream gel devoid of surfactant.

Thus, according to a particular embodiment, the present invention relates to a cosmetic or dermo-cosmetic composition as described above, said composition being formulated for topical application, in particular topical application of the skin, said composition being under the form of an aerosol, a simple or complex emulsion of the oil-in-water or water-in-oil type, a non-ionic vesicular dispersion, a cream, a gel, a gel cream , a lotion, an oil, a dispersion, a serum, a foam, an anhydrous body milk or balm,

in particular in the form of a day cream, a night cream, a powder, a solid stick, a foam or a spray,

in particular said composition being in the form of a cream gel devoid of surfactant.

When the cosmetic or dermo-cosmetic composition as defined above is used as an eyelash, eyebrow or skin makeup product, such as epidermis treatment cream, foundation, lipstick stick, eye shadow, blush, mascara or liner also called "eye liner", it can be in solid or pasty, anhydrous or aqueous form, such as oil-in-water or water-in-oil emulsions, non-ionic vesicular dispersions or even suspensions.

In a third object , and in one embodiment, the invention relates to the use, in particular the cosmetic use, of a cosmetic or dermo-cosmetic composition as described in the second object.

For the purposes of the present invention, “cosmetic use” means a non-pharmaceutical use, that is to say one which does not require therapeutic treatment, that is to say intended for any area of healthy skin.

In a particular embodiment, the invention relates to the use of a cosmetic or dermo-cosmetic composition as described above as a protective or cleansing composition for the human epidermis.

In a particular embodiment, the invention relates to the use of a cosmetic or dermo-cosmetic composition as described above as an anti-sun composition.

All the embodiments described in the first and second objects of the invention and characterizing the cosmetic or dermo-cosmetic combination or composition described above apply in this third object.

In a particular embodiment, the invention relates to the use of a cosmetic or dermo-cosmetic composition as described above for the protection of hair against ultraviolet rays.

Thus, in this particular embodiment, said cosmetic or dermo-cosmetic composition as defined above is in the form of shampoos, shower gels, foaming gels intended for intimate hygiene, hydro-alcoholic gel lotions , emulsions, non-ionic vesicular dispersions or hairsprays.

In a particular embodiment, the use of an association as described above for the protection of the body or any of its parts, against ultraviolet radiation, in particular against UVB solar radiation.

Thus, in this particular embodiment, said cosmetic or dermo-cosmetic composition comprising in particular a chicory extract (Védrine marketed by Silab).

In a particular embodiment, the use of a cosmetic or dermo-cosmetic composition as described above for the protection of the body or any of its parts, against ultraviolet radiation, in particular against radiation UVB sunscreens.

Thus, in this particular embodiment, said cosmetic or dermo-cosmetic composition comprising in particular a chicory extract (Védrine marketed by Silab).

A fourth object of the present invention is the use of an association according to the invention as defined above, or of a cosmetic or dermo-cosmetic composition according to the invention as defined above, in the treatment cosmetics for healthy skin that is sensitive and/or reactive.

By “sensitive and/or reactive skin” we mean any skin subject to a feeling of discomfort which may manifest itself by more or less diffuse and localized redness, itching, tightness, irritation, burning sensations.

According to another particular embodiment, the present invention relates to the cosmetic use of an association according to the invention, or of a cosmetic or dermo-cosmetic composition according to the invention as defined above, in the cosmetic treatment of sensitive and/or reactive skin.

For the purposes of the present invention, “cosmetic treatment” means a non-therapeutic treatment, that is to say intended for any area of healthy skin.

According to another particular embodiment, the present invention relates to the cosmetic use of an association according to the invention, or of a cosmetic composition according to the invention, to prevent and/or reduce the sensations of discomfort resulting from a sensitive or reactive skin, and in particular the sensations of itching, itching, tingling, tingling, itching or tightness.

According to another particular embodiment, the present invention relates to the cosmetic use of an association according to the invention as defined above, or of a cosmetic composition according to the invention as defined above, which can be administered by topical to prevent or slow the appearance of dysesthetic sensations on sensitive and/or reactive human skin.

By “dysesthetic sensations”, for the purposes of this application, we mean sensations felt in a skin area such as tingling, tingling, itching, burning, heating or tightness.

In a fifth subject , the invention relates to a pharmaceutical composition, in particular dermatological, comprising the association as defined above.

In other words, in this second subject, the invention relates to a pharmaceutical composition, in particular dermatological, comprising or consisting of a mixture of an oligofructan and at least one non-psychotropic phyto-cannabinoid.

All the embodiments defined in the first object of the invention concerning said association apply in this fifth object.

By “pharmaceutical composition” is meant any composition for pharmaceutical purposes, in particular a dermatological composition which can be brought into contact with the superficial parts of the human body, the skin, in particular the epidermis.

Another object of the present invention is a dermatological composition, comprising as active substance, an association as defined above, with a pharmaceutically acceptable excipient.

By “pharmaceutically acceptable excipient” is meant within the meaning of the invention any compound making it possible to facilitate the shaping of the composition and not modifying the nature of the biological activity of the active principle, with pharmaceutical use. A pharmaceutically acceptable excipient may be, for example, a solvent, plasticizer, lubricant, dispersion medium, absorption delaying agents, flow agent.

In a particular embodiment, the present invention relates to a dermatological composition as described above in which the oligofructan is present in an amount of 0.01 to 30% by mass relative to the total mass of the composition.

In a particularly preferred embodiment, the present invention relates to a dermatological composition as described above in which the oligofructan is present at a rate of 0.1% by mass relative to the total mass of the composition.

In a particularly preferred embodiment, the present invention relates to a dermatological composition as described above in which the oligofructan is present at 10% by weight relative to the total mass of the composition.

In a particular embodiment, the present invention relates to a dermatological composition as described above in which the non-psychotropic phyto-cannabinoid is present in an amount of 0.1 to 10% by mass relative to the total mass of the composition.

In a particular embodiment, the present invention relates to a dermatological composition as described above in which the non-psychotropic phyto-cannabinoid is present at 5% by mass relative to the total mass of the composition.

In a particular embodiment, the present invention relates to a dermatological composition as described above in which the non-psychotropic phyto-cannabinoid is present at a rate of 0.5% by mass relative to the total mass of the composition.

According to a particular embodiment, the present invention relates to a dermatological composition, comprising a combination as defined above, said composition comprising at least one other ingredient.

According to a particular embodiment, said ingredient is chosen in particular from agents derived from vitamin D such as 7-DHC (7-dehydrocholesterol).

According to another particular embodiment, said ingredient is chosen in particular from xanthic bases such as caffeine and/or theophylline and their esters.

According to one embodiment, said dermatological composition may also contain artificial tanning and/or browning agents for the skin (self-tanning agents), such as for example, tyrosine derivatives or dihydroxyacetone (DHA).

In a particular embodiment, the dermatological composition as defined above may also comprise at least one adjuvant agent chosen from: fatty substances, organic solvents, ionic or non-ionic thickeners, softeners, antioxidants, opacifiers, stabilizers, emollients, silicones, α-hydroxy acids, anti-foaming agents, moisturizing agents, vitamins, preservatives, surfactants, fillers, sequestrants, polymers, propellants and alkalizing or acidifying agents , dyes.

In a particular embodiment, the present invention relates to a dermatological composition as defined above, said composition being formulated for topical application.

More particularly, said dermatological composition is formulated for topical application to the skin.

In a particular embodiment, the present invention relates to a dermatological composition as defined above, said composition being in the form of an aerosol, a simple or complex emulsion of oil-in-water or water-in type. -oil, a non-ionic vesicular dispersion, a cream, a gel, a gel cream, a lotion, an oil, a dispersion, a serum, a mousse, body milk or anhydrous balm,

According to another particular embodiment, the present invention relates to a dermatological composition as defined above, said composition being in the form of a cream gel devoid of surfactant.

According to another particular embodiment, said dermatological composition as defined above is in the form of shampoos, shower gels, foaming gels intended for intimate hygiene, hydro-alcoholic gel lotions, emulsions or non-ionic vesicular dispersions.

In a sixth subject , the invention relates to the use of the association as described above or of a dermatological composition comprising said association as topical treatment, in particular as dermatological treatment.

According to a particular embodiment, the present invention relates to the association as defined above or to a dermatological composition comprising said association for its use to reduce the sensations of itching or pruritus, burning, heating or tightness of the skin.

According to a particular embodiment, the present invention relates to the association as defined above or to a dermatological composition comprising said association for its use in the treatment of dysbiosis.

By dysbiosis we mean the imbalance of the skin's microbiota. In cases of dysbiosis, the skin's immune responses may be altered and certain pathogenic bacterial species may develop further. Dysbiosis can be the cause of numerous skin discomforts and pathologies, such as acne, seborrheic dermatitis, pink cut, psoriasis or even atopic dermatitis.

According to a particular embodiment, the present invention relates to the association as defined above or to a dermatological composition comprising said association for its use in the treatment of hair dermatoses.

All the embodiments described in the first and fifth objects of the invention and characterizing the dermatological association or composition described above apply in this sixth object.

The following examples and figures illustrate the invention, without limiting its scope.

LIST OF FIGURES

There corresponds to photographs of two series of tests representing the assimilation of the two sugars and the mixture by S. aureus ; the A series corresponding to the assimilation of glucose and XOS; the B series corresponding to the assimilation of glucose and FOS.

There corresponds to a photograph of a petri dish showing the formation of colonies.

There corresponds to photographs of the results of the skin flora and inflammation on human skin a) presenting dysbiosis and after application of different gel creams for 28 days comprising respectively b) FOS, c) CBD and d) FOS associated with CBD.

EXAMPLES

Concrete examples illustrating the invention will now be given, without this being in any way limiting.

Various formulations have been prepared, preferably in the form of cream gels or emulsions of the W/O and O/W type .

Example 1: Fresh butter

Lanol P - Glycol Palmitate 1.00%

Isostearyl isostearate 10.00%

Sepiplus 265 2.00%

Ammonium Acrylate/Acrylamide Copolymer - Polyisobutene Polysorbate 20)

FOS (Fructans) 1.50%

CBD 0.50%

CBG 0.50%

Cetrimide BP 0.10%

Ethyl hexylglycerin 0.15%

Water Qsp 100

Example 2: Fresh Gel Cream

Simulgel NS100 2.00%

Caprylic/Capric/Triglyceride 15.00%

FOS (Fructans) 1.50%

CBD 1.50%

CBG 2.50%

Tocopheryl Acetate 0.50%

Methylparaben & Propylparaben 0.25%

Phenoxyethanol

Water Qsp 100

Example 3: Soothing Gel Cream

Simulgel NS100 2.00%

Caprylic/Capric/Triglyceride 15.00%

GGF Raffinose (Fructans) 4.50%

CBD 3.50%

Theophylline 1.50%

Tocopheryl Acetate 0.50%

Cetrimide BP 0.10%

Phenoxyethanol 0.15%

Water Qsp 100

Example 4: Moisturizing Gel Cream

Simulgel NS100 2.00%

Caprylic/Capric/Triglyceride 15.00%

XOS (Fructans) 1.50%

CBD 0.10%

CBG 2.50%

Tocopheryl Acetate 0.50%

Methylparaben & Propylparaben 0.25%

Phenoxyethanol 0.15%

Water Qsp 100

Example 5: Natural gel cream

Lecigel - Sodium Acrylates Copolymer (and) Lecithin 2.00%

Caprylic/Capric/Triglyceride 15.00%

Isononyl Isononanoate 4.00%

Butylene glycol Dicaprylate / Dicaparte 3.00%

Caffeine 2.00%

Raffinose (Fructans) 1.50%

CBG 4.50%

Fos (Fructanes) 1.50%

Phenoxyethanol 0.35%

Chlorphenesin 0.30%

Water Qsp 100

Example 6: Care Gel Cream

LANOL-TM99 3.50%

Octyldodecanol 1.50%

Phenoxyethanol & Ethylhexylglycerin 1.00%

Perfume/Fragrance 0.10%

Polyacrylate-13&Polyisobutene&Polysorbate20 (SEPIPLUS400) 1.00%

Glycerin 1.00%

Fructo Oligosaccharide (FOS) 3.00%

CBD 3.50%

CBG 3.50%

Calophyllum oil 2.00%

7-DHC (Pro-vitamin D) 0.05%

Sucrose 1.00%

Water Qsp 100

Example 7: Hair Serum

Water Qsp 100

Guar Hydroxypropyltrimonium Chloride 0.70%

Water Polyquaternium-7 Sericin & Guar Hydroxypropyltrimonium Chloride

Cetrimonium Chloride Behentrimonium Chloride 15.0%

XOS 3.00%

CBD 1.75%

Phenoxyethanol 0.10%

Perfume Qsp

Example 8 Shampoo

Water Qsp 100

Sodium Benzoate 0.50%

Tetrasodium Glutamate Diacetate 1.00%

Polyquaternium-10 0.25%

AMONYL™ 675 SB (Cocamidopropyl Hydroxysultaine) 10.00%

ORAMIX™ NS 10 (Decyl Glucoside) 1.00%

ORAMIX™ L30 EF (Sodium Lauroyl Sarcosinate) 5.00%

PROTEOL™ OAT PF (Sodium Lauroyl Oat Amino Acids) 5.00%

CBD 0.15%

FOS (Fructo Oligosaccharide) 3.00%

Sucrose 1.00%

Citric acid (50% solution) Qsp pH

Example 9 Tanning Sun Gel

Ethylhexyl Methoxycinnamate 7.50%

Ethylhexyl Triazone 3.00%

Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine 1.50%

Homomenthyl Salicylate 3.50%

EMOSMART™ L19 8.00%

FOS (Fructo Oligosaccharide) 3.00%

Caffeine 1.75%

SEPIMAX™ ZEN 0.15%

SEPINOV™ EMT 100 0.90%

Moringa oil 5.00%

Phenylpropanol (and) Caprylyl Glycol 0.50%

Cetrimide BP 0.10%

CBG 0.50%

Sucrose 1.00%

Water Qsp 100

Example 10 Study of metabolism by strains of skin flora

Micrococcus kristinae , Corynebacterium xerosis , Lactobacillus pentosus , Staphylococcus aureus , Gardnerella vaginalis and Propionibacterium acnes (from the Pasteur Institute collection) are cultured on their reference media. The media are cultured in the presence of a glucose carbon source, or prebiotic (FOS, XOS or GGF) at 0.5%. After 48 hours, the residual substrate content is quantified using liquid chromatography on an ion exchange column.

Glucose FOS XOS GGF Micrococcus kristinae +++ ++ +++ ++ Corynebacterium xerosis +++ +++ ++ +++ Lactobacillus pentosus +++ +++ +++ +++ Staphylococcus aureus +++ - - - Gardnerella vaginalis +++ + - - Propionibacterium acnes +++ - - -

Table 2. Proportion of sugars consumed depending on the type of strain. +++ corresponds to 60-110% of sugars consumed. ++ corresponding to 40-60% of sugars consumed. + corresponding to 20-40% of sugars consumed and – corresponding to 0-20% of sugars consumed.

Thus, prebiotics can be a source of carbon for saprophytic germs. They are not a source of carbon for the growth of pathogens. They are inhibitors of the growth of these pathogens.

Example 11 Study of the metabolism of XOS compared to that of glucose for two strains

These two strains come from the American Type Culture Collection (ATCC, Manassas, Virginia, USA):Staphylococcus aureussubsp. aureus Rosenbach (ATCC® 29213™) andStaphylococcus epidermis(Winslow and Winslow) Evans (ATCC® 14990™). Both strains were grown in Nutrient Broth #'2 medium (Oxoid, Basingstoke, UK) for 12 hours and were immediately frozen with 10% dimethyl sulfoxide at -80°C. Staph API codes are 6,736,153 ForS. aureusand 6,706,113 ForS. epidermidis. The capacity of the strains to assimilate glucose (Glu, 1%), xylo-oligosaccharide (XOS, 1%) and a mixture of Glu (1%) and XOS (1%) as a carbon source is compared here. This study is based on the one hand on the acidification (when the sugars are assimilated) or the alkalization (when the sugars are not assimilated) of the API Staph Medium medium (Biomerieux, Lyon France) and on the other hand, on the evaluation of the influence of two pHs (5.5 and 6.0) on the assimilation of 1% Glu, 1% XOS and the 1% Glu+1% XOS mixture by a mixed population ofS. aureusand ofS. epidermidis. The two strains ofS. aureusAndS. epidermidisare inoculated into sets of Falcon tubes containing 2 mL of API Staph medium.

This medium contains:

Yeast extract: 0.05%

Bactopeptone: 1% (animal protein hydrolyzate, bovine/porcine origin, as sole source of carbon and nitrogen)

NaCl: 0.5%

Trace elements: 0.1%.

Tube series include:

1 - White (2 tubes): 1.8 mL API Staph + 0.2 mL ultra pure water (EUP)

2 - Negative control (2 tubes): 1.8 mL API Staph + 0.2 mL EUP

3 - 1% Glucose (2 tubes): 1.8 mL API Staph + 0.2 mL Glucose (100 mg/mL EUP)

4 – 1% XOS (2 tubes): 1.8 mL API Staph + 0.2 mL FOS (100 mg/mL EUP)

5 – 1% Glu+ 1% XOS (2 tubes): 1.8 ml API Staph + 0.1 ml Glucose (200 mg/mL EUP) + 0.1 ml XOS (200 mg/mL EUP)

Series 2, 3, 4 and 5 are seeded with 20 μL of S. aureus , S. epidermidis and a mixture of the two strains (1:1) in phosphate buffer (pH = 7.4) after growth. for 12 hours in Nutrient Broth N°2 at 37°C.

The 5 series are placed under stirring at 37°C for 12 hours. At the end of growth, a volume of 5 μL of phenol red (10 mg in 0.02 N NaOH) is added to each tube and the interpretation is based on the reading of the colors according to the following diagram:

Red: pH ≥ 8.4, the strains exclusively assimilate the protein hydrolyzate contained in the API medium with alkalinization of the medium.

Orange: pH 6.6 ≤ pH < 8.4. The pH is that of the API Staph medium before inoculation (pH 7.0 – 7.4).

Yellow: pH < 6.6, the strains have assimilated sugar with acidification of the environment.

Example 12 Influence of pH on growth inhibition of S. aureus and of S. epidermis

For this part of the study, two pH values are considered: 5.5 and 6.0. The five tube series include:

1 - White (2 tubes)

2 – Negative control (non-assimilation, 2 tubes)

3 - 1% Glucose (2 tubes)

4 - 1% XOS (2 tubes)

5 - 1% Glucose + 1% XOS (2 tubes)

The pH of API Staph medium was adjusted to pH5.5 and 6.0 with hydrochloric acid (12N) and sterilized by filtration (0.45 μm).

Series 2, 3, 4 and 5 are inoculated with 20 μL of a mixture of the two strains (1:1) in phosphate buffer (pH = 7.4) after growth for 12 h in Nutrient Broth No. 2 at 37°C.

The 5 series are placed under stirring at 37°C for 12 hours. At the end of growth, 5 μL volumes of phenol red (10 mg in 0.02 N NaOH) are added to each tube and interpretation is based on color reading as previously described.

In addition, the viability of tubes 2, 3, 4 and 5 was evaluated on Chapman's medium (BD Difco # 211 805) for tubes seeded with a mixture of the two strains. With sugars, glucose is assimilated (acidic pH) but is not capable of assimilating XOS (alkaline pH).

For the mixture of the two sugars, the acidic pH reveals the assimilation of glucose only as shown in .

Example 13 Study of the evolution of skin flora and inflammation after application of different gel creams.

Samples were taken using a cotton swab soaked in sterile physiological serum, before and after application of the products. These samples are spread on Petri dishes containing Tryptone soya agar.

The Petri dishes are placed in an oven at 37°C and the readings are taken 36 hours later. Staphylococcus aureus colonies are counted visually – the color of the colonies is characteristic, they are bright yellow.

• Control Gel cream without active ingredients
• Gel cream 1 with FOS
• Gel Cream 2 with CBD
• Gel Cream 3 with FOS + CBD

The amount of Staphylococcus aureus was monitored throughout the study. Staphylococcus aureus colonies are yellow, very characteristic of this bacterial strain as shown in the .

The results are grouped in the table below.

Pathogenic Flora
Staphylococcus aureus Witness FOS CBD FOS + CBD Before the study +++ +++ +++ +++ 7 days later +++ ++ +++ ++ 14 days later +++ 27 +++ 15 21 days later +++ 20 +++ 12 28 days later +++ 17 ++ 5

Table 3. Monitoring of the population of Staphylococcus aureus colonies. + corresponding to 50 to 100 colonies, ++ corresponds to 100 to 1000 colonies, +++ corresponds to >1000 colonies.

Example 14 Study of the evolution of skin flora and inflammation on human skin after application of different gel creams.

Good results have been obtained with the FOS+CBD mixture. We notice an effect from the 1st week of treatment, with constant improvement thereafter, and total remission after the ^4th week at the end of the test.

At the same time, no improvement with the witness was noticed.

Inflammation
Witness FOS CBD FOS + CBD Before the study +++ +++ +++ +++ 14 days later +++ ++ + - 28 days later +++ ++ + -

Table 4. Visual evolution of inflammation on the skin after application of the cream

The results of the improvement of inflammation are presented in the .

Claims (16)

Association comprising or consisting of a mixture of an oligofructan and at least one non-psychotropic phyto-cannabinoid. Association according to claim 1, in which the oligofructan is an extract of plants or fruits chosen from: artichoke, Jerusalem artichoke, asparagus, banana, barley, beetroot, Brussels sprouts , melon, cantaloupe melon, chicory, garlic, grapefruit, leek, nectarine, onion, shallot onion, Spanish onion, white onion, white peach, spinach , rye, watermelon, wheat and zucchini,
in particular chosen from: rye, artichoke, asparagus and chicory. Association according to claim 1 or 2, in which the oligofructan is chosen from: fructo-oligosaccharide (FOS), xylo-oligosaccharides (XOS) and raffinose (GGF). Association according to one of claims 1 to 3, in which the non-psychotropic phyto-cannabinoid is chosen from: cannabidiol and cannabigerol. Association according to one of claims 1 to 4, in which the association is chosen from the mixture:

• fructo-oligosaccharide and cannabidiol;
• xylo-oligosaccharide and cannabidiol;
• raffinose and cannabidiol;
• fructo-oligosaccharide and cannabigerol;
• xylo-oligosaccharide and cannabigerol; And
• raffinose and cannabigerol.

Association according to one of claims 1 to 5, in which the ratio between the oligofructan and the phyto-cannabinoid is between 30:0.1 and 1:10. Cosmetic or dermo-cosmetic composition comprising the combination according to one of claims 1 to 6 in a cosmetically acceptable medium. Cosmetic or dermo-cosmetic composition according to claim 7, in which the oligofructan is present in an amount of 0.01 to 30% by mass relative to the total mass of the composition, preferably in an amount of 0.1 and 10%. . Cosmetic or dermo-cosmetic composition according to claim 7 or 8, in which the non-psychotropic phyto-cannabinoid is present in an amount of 0.1 to 10% by mass relative to the total mass of the composition, preferably in an amount of 0 .5 and 5%. Cosmetic or dermo-cosmetic composition according to one of claims 7 to 9, said composition being formulated for topical application, in particular topical application of the skin, said composition being in the form of an aerosol, of a simple emulsion or oil-in-water or water-in-oil type complex, a non-ionic vesicular dispersion, a cream, a gel, a gel cream, a lotion, an oil, a dispersion, a serum, a foam, a body milk or an anhydrous balm, in particular in the form of a day cream, a night cream, a powder, a solid stick, foam or spray,
in particular said composition being in the form of a cream gel devoid of surfactant. Cosmetic or dermo-cosmetic composition according to one of claims 7 to 10 further comprising agents derived from vitamin D such as 7-DHC. Cosmetic or dermo-cosmetic composition according to one of claims 7 to 11 further comprising agents derived from xanthic bases such as theophylline and/or caffeine. Cosmetic or dermo-cosmetic composition according to one of claims 7 to 12, further comprising at least one adjuvant agent chosen from: fatty substances, organic solvents, ionic or non-ionic thickeners, softeners, antioxidants, opacifiers , stabilizers, emollients, silicones, α-hydroxy acids, anti-foaming agents, moisturizing agents, vitamins, preservatives, surfactants, fillers, sequestrants, polymers, propellants and alkalizing agents or acidifiers, colorings. Cosmetic or dermo-cosmetic composition according to one of claims 7 to 13, for its use as a protective or cleansing composition for the human epidermis or as an anti-sun composition. Cosmetic or dermo-cosmetic composition according to one of claims 7 to 13, in the form of shampoos, shower gels, foaming gels intended for intimate hygiene, hydro-alcoholic gel lotions, emulsions, vesicular dispersions non-ionic or hair sprays,
for its use in protecting hair against ultraviolet rays. Composition comprising an association according to one of claims 1 to 6 or a cosmetic or dermo-cosmetic composition according to one of claims 7 to 13, and for its use for the protection of the body or any of its parts, against ultraviolet radiation, in particular against UVB solar radiation.