Isocetyl stearoyl stearate for reinforcing epidermal barrier function

Abstract

The present invention relates to isocetyl stearoyl stearate for its use in reinforcing and / or preventing a decrease in epidermal barrier function, in particular for enhancing the skin's protection against pollution. The present invention also relates to a cosmetic or dermatological composition comprising isocetyl stearoyl stearate and at least one cosmetically or dermatologically acceptable excipient for its use in reinforcing and / or preventing a decrease in epidermal barrier function, in particular for enhancing the skin's protection against pollution.

Description

[0001] DESCRIPTION

[0002] Isocetyl stearoyl stearate for strengthening the epidermal barrier function

[0003] TECHNICAL FIELD OF THE INVENTION

[0004] The present invention relates to the use of isocetyl stearoyl stearate and / or the use of compositions comprising isocetyl stearoyl stearate for strengthening and / or preventing the reduction of the epidermal barrier function, and more particularly for strengthening the protection of the skin against pollution, in particular atmospheric pollution.

[0005] STATE OF THE ART

[0006] The skin is made up of different layers that form a vital barrier for the body against the external environment. This barrier protects the body against external aggressions, particularly chemical, mechanical or infectious, and as such a number of defense reactions against environmental factors and / or xenobiotics occur at its level.

[0007] The skin is made up of three main parts, the superficial one, the epidermis, the internal part, the dermis and a deeper layer, the hypodermis, which interact.

[0008] The human epidermis is composed of four to five distinct layers (depending on the anatomical site) and four types of cells: keratinocytes, which are the vast majority, melanocytes, Langerhans cells, and Merkel cells. Each of these cell types contributes, through its own functions, to the essential role played in the body by the skin, in particular the role of protecting the body from external aggressions. This property is called the barrier function.

[0009] Epidermal cells proliferate in its deepest layer, the basal layer, and differentiate as they migrate to the upper layers to successively form the spinous layer, which consists of several layers of polyhedral cells arranged on the germinative layers; the granular layer, which consists of flattened cells containing distinct cytoplasmic inclusions; the keratohyalin granules; and finally the horny layer (or stratum corneum), which is the most superficial layer of the epidermis. The horny layer is made up of 10 to 30 layers of keratinocytes in the terminal stage of their differentiation, called corneocytes. Corneocytes, the constituent elements of the horny layer, are dead, flat cells containing water and keratin. The architecture of the stratum corneum is classically likened to a brick wall. The bricks represent the corneocytes.The intercorneocyte spaces are filled with organized lipids that constitute a hydrophobic "cement" around the corneocytes (partially ensuring the waterproofing of the stratum corneum). The intercorneocyte space fills with lipids during cornification. These lipids are organized into sheets and represent nearly 15% of the dry weight of the stratum corneum. The lipid composition of the stratum corneum is very different from that found in biological membranes. It is very poor in phospholipids and is mainly composed of ceramides (50% of the mass), cholesterol (25%), and free fatty acids (10-20%). These lipids form the intracellular cement of the stratum corneum (van Smeden et al., 2014).

[0010] In the 1990s, transmission electron microscopy analyses revealed the organization of intercorneocyte lipids into sheets, appearing as alternating transparent and electron-dense bands, parallel to the surface of the corneocytes. The lipids thus form multiple layers superimposed on each other. They are arranged perpendicular to the surface of the corneocytes and parallel to each other. The electron-dense bands correspond to the alignment of the polar heads of ceramides and the hydroxyl groups of fatty acids and cholesterol. The clear bands correspond to the apolar hydrocarbon chains of these lipids, aligned and positioned opposite each other. In vitro experiments have demonstrated that the specific lipid composition of the stratum corneum alone allows this particular arrangement of lipids into sheets (de Jager et al., 2005).

[0011] The supramolecular organization of intercorneocyte lipids plays a key role in establishing the physicochemical properties of the stratum corneum and consequently in maintaining a physiological water gradient. The structure of these lipid bilayers has specific assembly properties, either hexagonal (gel state) or orthorhombic (crystalline system whose unit cell is a rectangular parallelepiped), the latter being the majority (Bouwstra et al., 2008). The orthorhombic state represents the densest conformation and a balance between these two states is necessary for optimal barrier properties. A disruption in the proportion of the three families of lipids in the stratum corneum or an external stress (hot or cold) leads to a modification of the orthorhombic and hexagonal states and consequently a modification of the barrier function.

[0012] This lipid structure and the cohesion of epidermal cells participate in the skin's water exchange and the protective function or barrier function of the skin, on the one hand, against water loss (insensible water loss) and, on the other hand, against external aggressions (xenobiotics, pathogens, UV). The stratum corneum has long been considered a simple layer of dead cells without any real function. In reality, it is metabolically active and largely ensures the barrier function of the epidermis. However, this barrier is not absolute. Indeed, the skin participates in the control of the general homeostasis of the body by regulating the body's loss of water and electrolytes (Blank, 1953). It is permeable to small molecules (<500 daltons) to which it is exposed: only the degree of permeability varies.It is mainly linked to the physiological state of the skin and to the physicochemical properties of the compounds whose entry it is supposed to restrict (Schaefer and Redelmeier, 2010).

[0013] The stratum corneum, due to its structure and composition, constitutes the main barrier. Anatomically, two distinct pathways are available for the passage of substances: on the one hand, the transepidermal pathway and, on the other, the transfollicular pathway.

[0014] For the transepidermal route, diffusion of the molecule occurs either through the horny cells, which are mainly made up of hydrophilic proteins, or through the intercellular spaces of the horny layer, which are made up of lipids (Scheuplein, 1965). Due to its amphiphilic nature, the hydrolipidic intercellular domain constitutes a preferential diffusion channel for lipo- and water-soluble substances. Lipophilic substances diffuse through the hydrophobic zones of the intercellular lipid bilayers. More hydrophilic compounds migrate, on the one hand, through the hydrophilic zones of the intercellular lipid bilayers and, on the other hand, using the intracellular route.

[0015] Lipophilic substances can also take the transfollicular route via pilosebaceous follicles and / or sweat glands. However, this route remains a minority.

[0016] An alteration of the skin barrier and / or a break in the continuity of the skin surface can occur in the presence of external aggressions such as irritants (detergents, acids, bases, oxidants, reducers, concentrated solvents, toxic gases or fumes), mechanical stress (friction, shocks, abrasion, tearing of the surface, projection of dust or particles, shaving or hair removal), thermal or climatic imbalances (cold, dryness, heat, radiation), or xenobiotics (undesirable microorganisms, allergens) or internal aggressions such as psychological stress.

[0017] This alteration of the skin barrier can notably result in skin discomfort, sensory phenomena and in particular unpleasant phenomena. This sensation of skin discomfort can manifest itself in particular by tingling, tightness, heating, itching. These sensations of skin discomfort are more frequent 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 gestures such as shaving, hair removal, cleansing with toiletries or household products, the application of adhesives with dressings or patches, the fixing of prostheses or in the case of sporting, professional or simply lifestyle-related gestures and the use of clothing, tools or equipment generating localized friction.

[0018] Alteration of the skin barrier can also promote the appearance of micro-chapping or micro-fissures, particularly on the hands, feet and lips.

[0019] These feelings of skin discomfort affect everyone, especially those with sensitive or even intolerant skin. The concept of sensitive skin reflects the level of sensitivity of each individual's skin. While it is possible to have sensitive skin at any age, it is extremely common among babies and the elderly. Babies' skin is about one-fifth the thickness of adult skin. It is therefore extremely sensitive to chemical, physical, and microbial aggressions, as well as UV rays. The barrier function of adult skin, on the other hand, gradually weakens with age, in parallel with the slowing down of metabolic processes. Aging skin gradually leads to a lipid deficiency, which makes it more easily irritated by alkaline substances such as soap.

[0020] Thus, the alteration / weakening of the skin barrier allows increased penetration of exogenous substances (polluting agents, irritants or allergenic substances (also called allergens)), which can sometimes cause irritation or allergic reactions or even oxidative stress.

[0021] One of the causes of risk of alteration of the skin barrier is pollution.

[0022] The official definition of pollution is "a degradation of the environment by the introduction into the air, water or soil of materials not naturally present in the environment." As air pollution continues to increase, mainly due to human activity, measures have been put in place to prioritize research focused on reducing or controlling pollutant gas emissions. The consequences of this air pollution not only have global effects such as the greenhouse effect and the destruction of the ozone layer, but also at the local level on the health, well-being, skin and appendages of living beings.

[0023] The main pollutants have both natural and anthropogenic origins. The main pollutants that impact the skin include: solar radiation, polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), ozone (O3), nitrogen and sulfur oxides (NOx and SOx), particulate matter, also known as suspended particles, and tobacco smoke. In most cases, the effect of these pollutants on the skin is amplified when they are combined with other pollutants and / or solar radiation, particularly UV rays.

[0024] Air pollution (or atmospheric pollution) is a deterioration in air quality that can be characterized by measurements of chemical, biological, or physical pollutants (called "aerocontaminants"). It can have harmful consequences for human health, living beings, or the climate. Pollutants generally consist of cocktails of pollutants such as suspended particles, or other substances whose concentration and duration of presence are sufficient to produce a toxic or ecotoxic effect. Particulate matter corresponds to a mixture of solid, organic, and mineral particles suspended in the air (EPA - United States Environmental Protection Agency). They are composed, among other things, of soot carbon, benzo[a]pyrene (B(a)P) and other polycyclic aromatic hydrocarbons (PAHs), heavy metals, mineral dust, pollen, mold, and other biocontaminants.They are considered an indicator of global pollution (IARC Monograph - Volume 109, 2013). Particles are most often characterized based on their size. Indeed, their size makes it possible to determine their deposition zone in the respiratory tract (Shah et al., 2013). We generally speak of "PM" to designate particles, from the English "Particulate Matter", by adding the size to PM (PM10: 10pm; PM2.5: 2.5pm).

[0025] Suspended particles are fine solid particles transported by air or water. It is not the particles themselves that are responsible for the harmful effects but the molecules adsorbed on these particles (benzo[a]pyrene, heavy metals, pesticides, etc.). They can generate oxidative stress on the skin and are thus at least partly responsible for skin aging. They are suspected of inducing the formation of wrinkles and the appearance of pigment spots.

[0026] One of the most well-known air pollutants is benzo[a]pyrene (B(a)P) and is found in significant quantities in particles. It is a persistent air pollutant of concern, belonging to the family of Polycyclic Aromatic Hydrocarbons (PAHs), and is a highly carcinogenic mutagenic agent. It is notably found in cigarette smoke, fumes emitted by exhaust pipes, fumes from road surfaces, fossil fuel combustion (coal, oil, shale) and incomplete combustion of organic matter such as forest fires (INERIS Report, 2006). B(a)P is biotransformed through multiple pathways, most of which can lead to epoxide intermediates involved in their genotoxicity.

[0027] In addition, pollution has an effect on the reduction of the protective barrier function of the skin by modifying the hydrolipidic film. It will lead to an alteration of cell renewal which will then be less rapid, the skin then appears duller, less firm. It is also known that pollution prematurely ages the skin, by increasing the production of free radicals which destroy cells and cause the destruction of collagen and elastin fibers. Pollutants would also have an impact on the appearance and aggravation of skin pathologies such as redness, sensitivity, acne, eczema, psoriasis.

[0028] The percutaneous route is one of the main routes of exposure to pollutants and PAHs (approximately 200 compounds), particularly for non-volatile or low-volatile compounds such as B(a)P. These molecules can cross the skin by simple passive diffusion of the lipid barrier of the stratum corneum and lead to the formation of carcinomas after their metabolism (with formation of epoxides). However, the levels of B(a)P or pollutants absorbed via the skin remain low when the skin barrier is not impaired.

[0029] It is therefore essential to preserve and even improve this skin barrier function, especially since pollution is increasingly present in our daily environment, in order to avoid and limit the absorption of pollutants by the skin barrier.

[0030] SUMMARY OF THE INVENTION

[0031] The inventors have surprisingly demonstrated that isocetyl stearoyl stearate promotes the strengthening of the epidermal barrier function and prevents a reduction in this epidermal barrier function, particularly under the effect of environmental factors, but also makes it possible to limit, or even prevent, the passage of pollutants into the skin, which strengthens the skin's protection against pollution.

[0032] Indeed, the inventors have demonstrated that isocetyl stearoyl stearate makes it possible to stabilize the intercorneocyte spaces of the stratum corneum, and more particularly the change in state of the lipids present in the intercorneocyte spaces, said change in state being observed in particular under the effect of temperature.

[0033] To evaluate the change in the organization of the lipid phases of the intercorneocyte spaces of the stratum corneum, the inventors analyzed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) the variation, under the effect of temperature, of the fundamental vibration bands of the aliphatic vCEE chains of these lipids, and, more particularly, the position of the absorption band corresponding to the elongation of the CEE (stretching). For example, an increase in the temperature of the skin surface causes a shift of this band towards high wave numbers. This shift reflects the fact that the lipids, in the stratum corneum, adopt, under the effect of heat, a less ordered conformation accompanied by an increase in the fluidity of the hydrocarbon chains which fill the intercorneocyte spaces.This reflects a reduction in the barrier function which allows the freer passage of exogenous molecules into the epidermis.

[0034] It has also been shown that isocetyl stearoyl stearate, through its barrier strengthening function, helps limit the passage of polluting agents into the epidermis.

[0035] According to a first aspect, the invention relates to isocetyl stearoyl stearate for its use in strengthening and / or preventing a reduction in the epidermal barrier function.

[0036] The invention also relates to the use of isocetyl stearoyl stearate for strengthening and / or preventing a reduction in the epidermal barrier function.

[0037] The invention also relates to the use of isocetyl stearoyl stearate for the preparation of a cosmetic or dermatological composition for strengthening and / or preventing a reduction in the epidermal barrier function.

[0038] The invention also relates to a method for enhancing and / or preventing a decrease in epidermal barrier function comprising administering to a person in need thereof an effective amount of isocetyl stearoyl stearate.

[0039] According to a second aspect, the invention relates to a cosmetic or dermatological composition comprising isocetyl stearoyl stearate with at least one cosmetically or dermatologically acceptable excipient (composition according to the invention) for its use in strengthening and / or preventing a reduction in the epidermal barrier function.

[0040] The invention also relates to the use of a composition according to the invention for strengthening and / or preventing a reduction in the epidermal barrier function.

[0041] The invention also relates to the use of a composition according to the invention for the preparation of a medicament for strengthening and / or preventing a reduction in the epidermal barrier function.

[0042] The invention also relates to the use of a composition comprising isocetyl stearoyl stearate, and preferably at least one cosmetically or dermatologically acceptable excipient, for the preparation of a cosmetic or dermatological composition for strengthening and / or preventing a reduction in the epidermal barrier function.

[0043] The invention also relates to a method for strengthening and / or preventing a reduction in the epidermal barrier function comprising administering to a person in need thereof an effective amount of a composition according to the invention.

[0044] DETAILED DESCRIPTION OF THE INVENTION

[0045] Definitions

[0046] By "approximately" is meant, in the present description, that the value concerned may be 10% lower or higher, in particular 5%, in particular 1%, than the indicated value. By "topical application" is meant, within the meaning of the present invention, an application to the skin (including the scalp), and the mucous membranes, preferably the skin.

[0047] For the purposes of the present invention, the term "cosmetically or dermatologically acceptable" means that which is useful in the preparation of a cosmetic or dermatological composition, which is generally safe, non-toxic and neither biologically nor otherwise undesirable and which is acceptable for cosmetic or dermatological use, in particular by topical application to the skin.

[0048] For the purposes of the present invention, the term "epidermal barrier" means the cellular structures of the epidermis, in particular the tissue barrier formed by the corneocytes and the intercellular lipid cement (lipid phase), namely the horny layer (also called stratum corneum - SC for short).

[0049] For the purposes of the present invention, the term "epidermal barrier function" means the protective function of the epidermis, in particular against external aggressions.

[0050] Intercorneocyte spaces mean spaces containing a lipid phase that are located between the corneocytes of the stratum corneum.

[0051] By "stabilization of intercorneocyte spaces" is meant, within the meaning of the present invention, a reduction in the destabilization of intercorneocyte spaces, in particular under the action of environmental factors, and which therefore has the effect of limiting or opposing the passage into the skin of exogenous molecules, such as chemical or microbial agents and in particular irritant agents, allergenic agents (or allergens), or even polluting agents, which can cause irritations or allergic reactions or even oxidative stress, in skin in particular exposed to environmental factors.

[0052] For the purposes of the present invention, the term "environmental factors" means external conditions such as heat or cold which induce a variation in skin temperature capable of destabilizing intercorneocyte spaces. In a preferred embodiment, heat such as that of a summer period or due to exposure to the sun can induce an increase in skin temperature and cause fluidification of the lipids of the intercorneocyte spaces for the purposes of the present invention.

[0053] Isocetyl stearoyl stearate

[0054] Isocetyl stearoyl stearate is the INCI name for the compound with the IUPAC name 14-methylpentadecyl 12-octadecanoyloxyoctadecanoate (CAS No. 97338-28-8), also known as isohexadecyl 12-[(l-oxooctadecyl)oxy]octadecanoate. It has the following formula:

[0055] In the context of the present invention, isocetyl stearoyl stearate is useful for strengthening and / or preventing a decrease in the epidermal barrier function. The barrier function can be reduced under the effect of environmental factors such as cold or heat, in particular heat.

[0056] Indeed, isocetyl stearoyl stearate has been shown to have a stabilizing effect on intercorneocyte spaces.

[0057] Isocetyl stearoyl stearate thus makes it possible, in particular, to limit the passage of exogenous molecules into the skin. Exogenous molecules can be in particular irritants (hygiene products, solvents, etc.), allergenic agents (or allergens) (perfumes, house dust, microbial agents, etc.), or polluting agents (polycyclic aromatic hydrocarbons (PAHs) (e.g. soot carbon, benzo[a]pyrene (B(a)P)), volatile organic compounds (VOCs), ozone O3, nitrogen oxides (NOx), sulfur oxides (SOx), suspended particles including tobacco smoke, etc.), more particularly polluting agents. Preferably, the exogenous molecules are polluting agents and more particularly atmospheric polluting agents such as polycyclic aromatic hydrocarbons (PAHs) (e.g.soot carbon, benzo[a]pyrene (B(a)P)), volatile organic compounds (VOCs), ozone O3, nitrogen oxides (NOx), sulfur oxides (SOx), or suspended particles including tobacco smoke.

[0058] Isocetyl stearoyl stearate also helps to strengthen the skin's protection against pollution, particularly atmospheric pollution, and therefore acts as an anti-pollution agent.

[0059] Isocetyl stearoyl stearate is also useful for preventing irritations and / or allergic reactions, particularly due to exogenous molecules, in particular such as pollutants, irritants or allergenic substances (also called allergens). This use is particularly advantageous for subjects whose skin is exposed to environmental factors. Isocetyl stearoyl stearate is also useful for maintaining the firmness and / or radiance of the skin, and / or for preventing skin aging, in particular preventing the loss of firmness and / or radiance of the skin, particularly linked to atmospheric pollution.

[0060] Compositions

[0061] In the context of the present invention, the compositions according to the invention are useful for strengthening and / or preventing a reduction in the epidermal barrier function. The barrier function can be reduced under the effect of environmental factors such as cold or heat, in particular heat.

[0062] Indeed, the compositions according to the invention have a stabilizing effect on intercellular spaces.

[0063] The compositions according to the invention thus make it possible, in particular, to limit the passage of exogenous molecules into the skin. The exogenous molecules may be, in particular, irritants (hygiene products, solvents, etc.), allergenic (or allergen) agents (perfumes, house dust, microbial agents, etc.), or even polluting agents (polycyclic aromatic hydrocarbons (PAHs) (e.g., soot carbon, benzo[a]pyrene (B(a)P)), volatile organic compounds (VOCs), ozone O3, nitrogen oxides (NOx), sulfur oxides (SOx), suspended particles including tobacco smoke, etc.), more particularly polluting agents. Preferably, the exogenous molecules are polluting agents and more particularly atmospheric polluting agents such as polycyclic aromatic hydrocarbons (PAHs) (e.g.,soot carbon, benzo[a]pyrene (B(a)P)), volatile organic compounds (VOCs), ozone O3, nitrogen oxides (NOx), sulfur oxides (SOx), or suspended particles including tobacco smoke.

[0064] The compositions according to the invention thus also make it possible to strengthen the protection of the skin against pollution, and more particularly atmospheric pollution, and therefore to act as an anti-pollution agent.

[0065] The compositions according to the invention are also useful for preventing irritations and / or allergic reactions, in particular due to exogenous molecules, in particular such as polluting agents, irritants or allergenic substances (also called allergens). This use is particularly advantageous for subjects whose skin is exposed to environmental factors.

[0066] The compositions according to the invention are also useful for maintaining the firmness and / or radiance of the skin, and / or for preventing skin aging, in particular preventing the loss of firmness and / or radiance of the skin, in particular linked to atmospheric pollution.

[0067] According to one embodiment, the compositions according to the invention contain from 0.1% to 10%, in particular from 0.2% to 8%, in particular from 0.5% to 8%, more particularly from 0.8% to 6%, of isocetyl stearoyl stearate by weight relative to the total weight of the composition.

[0068] According to another embodiment, the compositions according to the invention contain from 0.1% to 6%, in particular from 0.1% to 5%, in particular from 0.1% to 4%, more particularly from 0.1% to 3%, of isocetyl stearoyl stearate by weight relative to the total weight of the composition.

[0069] According to another embodiment, the compositions according to the invention contain from 0.2% to 6%, in particular from 0.5% to 5%, in particular from 0.6% to 4%, more particularly from 0.8% to 2%, of isocetyl stearoyl stearate by weight relative to the total weight of the composition.

[0070] According to another embodiment, the compositions according to the invention contain from 0.2% to 1.8%, in particular from 0.5% to 1.5%, in particular from 0.6% to 1.3%, more particularly from 0.8% to 1.3%, of isocetyl stearoyl stearate by weight relative to the total weight of the composition. Preferably, the compositions according to the invention contain approximately 1% of isocetyl stearoyl stearate by weight relative to the total weight of the composition.

[0071] According to one embodiment, the compositions according to the invention do not comprise beta-sitosterol. According to one embodiment, the compositions according to the invention do not comprise glyceryl tri-2-ethylhexanoate.

[0072] According to one embodiment, the compositions according to the invention do not comprise the peptide whose sequence is listed in the Genbank database under accession number WON20281, version WON20281.1, available in particular in version GenBank Release 260 of April 15, 2024, which peptide is also described in US 11,628,133 as corresponding to a peptide having the sequence SEQ ID NO: 1.

[0073] According to one embodiment, the compositions according to the invention do not comprise the product of bioconversion by Lactobacillus arizonensis of Simmondsia chinensis. In particular, the compositions of the invention do not comprise supernatant obtained by bioconversion by Lactobacillus arizonensis of Simmondsia chinensis as described in US 2021 / 0059929. According to one embodiment, the compositions according to the invention do not comprise Rosa gallica flower extract, in particular rose extract.

[0074] The embodiments described above are not mutually exclusive and may be combined according to the needs and knowledge of those skilled in the art.

[0075] The compositions according to the invention are advantageously intended for topical application, in particular by application to the skin. They are therefore more particularly in a form suitable for topical application. The composition according to the invention can in particular be applied to sensitive, fragile and / or reactive skin.

[0076] The compositions according to the invention may thus be presented in the forms which are usually known for topical administration, that is to say in particular lotions, milks, emulsions, serums, balms, ointments, masks, creams, dispersions, gels, mousses or sprays. Preferably, it is a milk.

[0077] They can also be presented in solid form, such as a stick, or applied to the skin in the form of an aerosol. These compositions may notably be presented in the form of an oily solution or an emulsion such as an oil-in-water emulsion, a water-in-oil emulsion or a multiple emulsion.

[0078] The following examples illustrate the invention without limiting its scope.

[0079] EXAMPLES

[0080] Example 1: Evaluation of the impact of temperature on the organization of the lipid matrix

[0081] To evaluate the change in organization of the lipid phases of the stratum corneum, the inventors analyzed, by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR for "Attenuated total reflectance - Fourier transform infrared Spectroscopy" in English), the variation, under the effect of temperature, of the fundamental vibration bands of the aliphatic CEE chains of these lipids. More particularly, the position of the absorption band, corresponding to the elongation of the CEE ("stretching"), is located around the wave number 2850 cm' 1 The position of the vCEE bond elongation peak band is characteristic of lipid organization and can be correlated with barrier function (Boncheva et al., 2008). Materials and methods:

[0082] ATR-FTIR measurements were performed on 8 human skin donors.

[0083] Skin explants

[0084] Human skin samples were obtained from cosmetic surgery. The skin was cut longitudinally to a thickness of approximately 450 μm using an electric dermatome (Acculan® 3TI, Aesculap®). The skin samples thus collected included the entire epidermis and part of the dermis.

[0085] ATR-FTIR measurements

[0086] ATR-FTIR spectroscopy (Perkin Elmer) was used to examine the temperature-dependent variation of the fundamental vCH2 vibration bands of aliphatic chains. For this purpose, skin samples were heated with a ramp of 1°C / min and ATR-FTIR spectra were collected at regular intervals between 28°C and 42°C. The spectra were recorded using TimeBase software (Perkin Elmer) for kinetics.

[0087] Results :

[0088] The results of ATR-FTIR measurements performed on human skin explants from 8 donors are presented in Table 1.

[0089] [Table 1]

[0090] ESM: standard error of the mean

[0091] Table 1 shows the impact of temperature on the CEE bond stretching peak band, which is characteristic of the lipid organization of the stratum corneum. A significant difference in lipid organization is observed between skin at 28°C and skin at 42°C, with a shift in the CEE bond stretching peak band of 2851.06 cm' 1 at 28°C around 2851.87 cm' 1at 42°C (p-value < 0.05). An increase in the skin surface temperature thus causes a shift of this band towards high wave numbers. This shift reflects the fact that the lipids in the stratum corneum adopt, under the effect of heat, a less ordered conformation accompanied by an increase in the fluidity of the hydrocarbon chains that fill the intercorneocyte spaces. The increase in temperature from 28°C to 42°C at the skin surface thus modifies the lipid organization and consequently alters the skin barrier function.

[0092] Example 2: Evaluation of the impact of isocetyl stearoyl stearate on the reorganization of the barrier function to limit the passage of pollutants, in particular benzo[a]pyrene In order to evaluate the impact of isocetyl stearoyl stearate on the organization of lipids in the stratum corneum and the barrier function, in vitro, studies of the cutaneous passage of a known pollutant, benzo[a]pyrene (B(a)P), were developed and carried out.

[0093] On the same donors, ATR-FTIR measurement and B(a)P skin penetration were evaluated to link lipid organization and “outside-in” modulations of skin barrier function, when the skin is heated up to 42°C. First, it was shown that an increase in temperature from 32°C to 42°C at the skin surface modifies lipid organization and impairs skin barrier function, as shown by the increase in B(a)P skin penetration.

[0094] Second, the impact of pretreatment with isocetyl stearoyl stearate at a concentration of 1% was evaluated on the modification of the lipid organization of the stratum corneum and the skin penetration of B(a)P caused by temperature elevation.

[0095] Materials and methods:

[0096] Compounds

[0097] The compounds presented in Table 2 were used in this study.

[0098] [Table 2] * Benzo[a]pyrene labeled with carbon 14

[0099] Solubility of B(a)P

[0100] The solubility of B(a)P is well documented in the literature. Due to its physicochemical properties, B(a)P has very low solubility in water. Episuite software predicts a solubility of 13.3 pg / L in water, and experimental data have confirmed these results at 25°C (May et al. 1983).

[0101] Guidelines

[0102] The percutaneous passage study was performed in accordance with the following guidelines:

[0103] • OECD Directive 428: “OECD Guideline for the testing of chemicals - Skin absorption: in vitro method” (Directive 428 - April 13, 2004);

[0104] • Directive SCCS / 0970 / 06: “Basic criteria for the in vitro assessment of dermal absorption of cosmetic ingredients” (updated version of March 2006).

[0105] Skin explants

[0106] Human skin samples were obtained from cosmetic surgery. The skin was cut longitudinally to a thickness of approximately 450 μm using an electric dermatome (Acculan® 3TI, Aesculap®). The skin samples thus collected included the entire epidermis and part of the dermis.

[0107] Experimental study

[0108] For the percutaneous passage study, two temperatures were therefore used: 32°C and 42°C. The classic temperature found at the skin surface is 32°C. This temperature corresponds to the temperature at the skin surface in vivo and is commonly used for percutaneous passage studies. From 40°C, lipid disorganization (modification of the orthorhombic state) was observed during ATR-FTIR studies, which can lead to a modification of the percutaneous passage of pollutants. Based on these results, a second temperature of 42°C was chosen to be able to observe the lipid disorganization during the percutaneous passage experiment.

[0109] Human skin explants were placed on Franz diffusion cells (1.2 cm 2). The receiving medium of each Franz diffusion cell consisted of a 0.9% NaCl solution and 4% bovine serum albumin (BSA). The human skin explants were then pretreated with the vehicle alone (dimethicone) (control) or with a dimethicone solution containing Tisocetyl stearoyl stearate or compritol at 1% (w / w). The applied volume was 10 μL / cm 2 .

[0110] After 30 min, a 0.5% B(a)P solution in acetone was applied to the skin explants at a rate of 10 μl / cm 2 (or 52 pg / cm 2 ).

[0111] After 24 hours, the surface of the skin explants was cleaned twice with water, then twice with acetonitrile, then twice with a half-disc of Whatman™ filter paper. The stratum corneum was then removed from each explant by applying 15 successive D-Squame® adhesives.

[0112] The amount of B(a)P was then measured in the different compartments: skin surface, stratum corneum, skin (dermis and epidermis) and receiving medium. The total recovery of B(a)P should be between 85% and 115% of the applied dose in accordance with OECD 428 and SCCS / 0970 / 06 guidelines.

[0113] It should be noted that, before carrying out the study, a measurement of the integrity of the skin is carried out for each explant in order to verify that the transepidermal water loss (TEWL) is less than or equal to 13 g / m 2 / h. This allows us to check that the skin explants do not have small lesions not visible to the naked eye, which could distort the results of the study.

[0114] The skin penetration study was performed on human skin explants from 11 donors. All conditions in Table 3 were evaluated once on one explant from each donor.

[0115] [Table 3]

[0116] Inter-group comparisons were performed by ANOVA statistical analysis using Graph Pad Prism software.

[0117] Results The total recovery for all diffusion cells was within the acceptance criteria, between 90.43% and 95.17% of the applied dose, and validates the experiment. The percentages found in the different compartments are summarized in Table 4.

[0118] [Table 4]

[0119] * sum of the percentages found in the skin and the receiving medium ** P<0.01 versus condition at 32°C

[0120] NSS: not statistically significant versus 32°C condition

[0121] The majority of the applied dose of B(a)P was recovered from the skin surface (up to 95.17% of the applied dose).

[0122] At 32°C, we observe that the bioavailability of B(a)P (skin + receptor medium) remains low at 32°C, namely approximately 2.97% of the dose applied at 32°C, i.e. when the skin barrier is intact. Thus, the skin barrier prevents pollutants (here B(a)P) from crossing the layers of the skin and therefore plays a protective role.

[0123] However, at 42°C, for the dimethicone control solution, significant quantities of B(a)P are found in the skin (epidermis + dermis). For compounds with physicochemical properties close to B(a)P (lipophilic compounds, pollutants), the skin thus acts as a reservoir which traps these compounds before their transformation by skin enzymes and their possible release into the bloodstream.

[0124] The bioavailability of B(a)P increases significantly when the skin temperature increases and thus goes from 2.97% at 32°C to 8.54% at 42°C of the applied dose. These results obtained on the percutaneous passage of B(a)P are well correlated with the results obtained from ATR-FTIR measurements. Thus, the increase in temperature reflects a modification of the lipid organization and therefore an alteration of the skin barrier. After pretreatment with compritol, the bioavailability of B(a)P increases significantly when the skin temperature increases to 42°C. Compritol does not seem to have any protective effect on the skin barrier and therefore does not prevent or limit the passage of pollutants.

[0125] On the other hand, surprisingly, the inventors were able to observe that after pre-treatment with 1% isocetyl stearoyl stearate, the bioavailability of B(a)P is not significantly increased when the skin temperature reaches 42°C. Thus, even if the skin is heated to 42°C, leading to a disorganization of the lipids, the passage of B(a)P is not increased at all when the same skin is pre-treated with isocetyl stearoyl stearate.

[0126] The results obtained for the percutaneous passage of B(a)P after 24 hours of topical application are well correlated with the results obtained from ATR-FTIR measurements. These data showed that the modification of lipid organization around 42°C induces a weakening of the skin barrier function and increases the bioavailability of compounds such as external pollutants such as B(a)P. This shows that the use of isocetyl stearoyl stearate significantly improves the barrier function. Pretreatment with 1% isocetyl stearoyl stearate stabilizes the lipid organization and improves the barrier function as demonstrated by the skin penetration study of B(a)P. The use of isocetyl stearoyl stearate thus also acts as an anti-pollution agent by limiting the passage of the pollutant through the skin barrier.

[0127] BIBLIOGRAPHICAL REFERENCES

[0128] IARC Monograph - Volume 109, 2013;

[0129] Rapport INERIS, 2006 ;

[0130] Directive OECD 428 : « OECD Guideline for the testing of chemicals - Skin absorption: in vitro method » (Directive 428 - 13 avril 2004) ;

[0131] Directive SCCS / 0970 / 06 : « Basic criteria for the in vitro assessment of dermal absorption of cosmetic ingredients » (version mise à jour de mars 2006) ;

[0132] Blank, 1953, Journal of Investigative Dermatology, 259-271 ;

[0133] Boncheva et al., 2008, Biochimica et Biophysica Acta, 1778, 1344-1355 ;

[0134] Bouwstra et al., 2008, International Journal of CosmeticScience, 30(5), 388-390 ; de Jager et al., 2005, Journal of Lipid Research, 46, 2649-2656 ;

[0135] May et al. 1983, Journal Chemistry Reference Data, 28, 197-200; Schaefer and Redelmeier, 2011, Contact Dermatitis, chapitre 11 intitulé « Skin penetration », ISBN : 978-3-642-03826-6 ;

[0136] Shah et al., 2013, Lancet 382, ​​1039-1048;

[0137] Scheuplein, 1965, Journal of Investigative Dermatology, 45(5), 334-346; • van Smeden et al., 2014, Biochimica et Biophysica Acta, 1841, 295-313.

Claims

CLAIMS 1. Isocetyl stearoyl stearate for its use to strengthen and / or prevent a reduction in the epidermal barrier function, to strengthen the protection of the skin against pollution.

2. Isocetyl stearoyl stearate for its use according to claim 1, to limit the passage into the skin of exogenous molecules, the exogenous molecules being polluting agents.

3. Isocetyl stearoyl stearate for its use in preventing irritations and / or allergic reactions, in particular due to exogenous molecules, the exogenous molecules preferably being polluting agents.

4. Cosmetic or dermatological composition comprising isocetyl stearoyl stearate and at least one cosmetically or dermatologically acceptable excipient for its use in strengthening and / or preventing a reduction in the epidermal barrier function, in order to strengthen the protection of the skin against pollution.

5. Composition for use according to claim 4, to limit the passage of exogenous molecules into the skin, the exogenous molecules being polluting agents.

6. Cosmetic or dermatological composition comprising isocetyl stearoyl stearate and at least one cosmetically or dermatologically acceptable excipient for its use in preventing irritations and / or allergic reactions, in particular due to exogenous molecules, the exogenous molecules preferably being polluting agents.

7. Composition for use according to any one of claims 4 to 6, characterized in that it comprises from 0.1% to 10% of isocetyl stearoyl stearate by weight relative to the total weight of the composition.

8. Composition for its use according to any one of claims 4 to 7, characterized in that it comprises from 0.2% to 1.8%, preferably from 0.5% to 1.5%, from 0.6% to 1.3%, or from 0.8% to 1.3%, of isocetyl stearoyl stearate by weight relative to the total weight of the composition.

9. Composition for use according to any one of claims 4 to 8, characterized in that it is in a form suitable for topical application.

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