isocetyl stearoyl oxy stearate for enhancing epidermal barrier function

Abstract

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

Description

Technical Field

[0001] This invention relates to the use of isocetyl stearoxy stearate and / or compositions containing isocetyl stearoxy stearate in enhancing and / or preventing the reduction of epidermal barrier function, and more specifically, to enhancing the skin's protection against pollution, particularly air pollution. Background Technology

[0002] The skin is composed of different layers, forming an important barrier against the external environment. This barrier protects the body from external aggressors, especially chemical, mechanical, or infectious aggressors. Therefore, many defensive responses against environmental factors and / or xenobiotics occur at this level.

[0003] The skin consists of three main parts: the epidermis, the outermost layer; the dermis, the innermost layer; and a deeper layer, the subcutaneous tissue, which interact with each other.

[0004] The human epidermis consists of four to five distinct layers (depending on the anatomical location) and four cell types: keratinocytes (the most numerous), melanocytes, Langerhans cells, and Merkel cells. Each of these cell types contributes to the vital role of the skin in the body through its specific functions, particularly its role in protecting the body from external aggressors. This property is known as the barrier function.

[0005] Epidermal cells proliferate in the deepest layer, the basal layer, and differentiate as they migrate upwards, successively forming the stratum spinosum, which consists of multiple layers of polyhedral cells arranged in the germinal layer; the stratum granulosum, which consists of flattened cells containing unique cytoplasmic inclusions called keratinocytes; and finally the stratum corneum. stratum corneum The stratum corneum is the outermost layer of the epidermis. It consists of 10 to 30 layers of keratinocytes in the final stage of differentiation. These cells are called keratinocytes. The keratinocytes, the components of the stratum corneum, are dead, flattened cells containing water and keratin. The structure of the stratum corneum is often compared to a brick wall. The "bricks" represent the keratinocytes. The intercellular spaces are filled with orderly arranged lipids, which form a hydrophobic "matrix" around the keratinocytes (partially ensuring the impermeability of the stratum corneum). During keratinization, the intercellular spaces are filled with lipids. These lipids are organized into layers and account for approximately 15% of the dry weight of the stratum corneum.

[0006] The lipid composition of the stratum corneum differs significantly from that of biological membranes. It has a low phospholipid content and is primarily composed of ceramides (50% by mass), cholesterol (25% by mass), and free fatty acids (10% to 20% by mass). These lipids form the intracellular matrix of the stratum corneum (van Smeden et al., 2014).

[0007] In the 1990s, transmission electron microscopy revealed the layered organization of intercellular lipids in keratinocytes, characterized by alternating transparent and electron-dense bands parallel to the keratinocyte surface. The lipids thus form multiple superimposed layers. These layers are perpendicular to the keratinocyte surface and arranged parallel to each other. The electron-dense bands correspond to the arrangement of the polar head groups of ceramides with the hydroxyl groups of fatty acids and cholesterol. The transparent bands correspond to the nonpolar hydrocarbon chains of these lipids, aligned and relatively positioned. In vitro experiments have demonstrated that only a specific lipid composition of the stratum corneum can achieve this specific lipid layering (de Jager et al., 2005).

[0008] The supramolecular organization of interstitial lipids plays a crucial role in establishing the physicochemical properties of the stratum corneum, and therefore also in maintaining the physiological water gradient. These lipid bilayers exhibit specific assembly properties, ranging from hexagonal (gel state) to orthorhombic (cuboidal crystal system), with the latter being predominant (Bouwstra et al., 2008). The orthorhombic state represents the most compact conformation, and a balance between these two states is necessary for optimal barrier properties. Imbalances in the proportions of the three lipid classes in the stratum corneum, or external stresses (heat or cold), lead to alterations in the orthorhombic and hexagonal states, thereby changing barrier function.

[0009] This lipid structure, along with the cohesion of epidermal cells, plays a role in the skin's water exchange and protective barrier function, preventing both transepidermal water loss and protection against external aggressors (xenobiotics, pathogens, ultraviolet radiation). The stratum corneum has long been considered a simple layer of dead cells with no real function. In fact, it is metabolically active and primarily responsible for the epidermal barrier function.

[0010] However, this barrier is not absolute. In fact, the skin participates in controlling overall body homeostasis by regulating the loss of water and electrolytes (Blank, 1953). It is permeable to small molecules (< 500 Daltons) that it comes into contact with: only the degree of permeation varies. This is mainly related to the physiological state of the skin and the physicochemical properties of the compounds that should restrict its entry (Schaefer and Redelmeier, 2010).

[0011] The stratum corneum, with its structure and composition, constitutes the main barrier.

[0012] Anatomically, substances can pass through two different pathways: one is the transepidermal pathway, and the other is the hair follicle pathway.

[0013] For the transepidermal pathway, molecular diffusion occurs either through stratum corneum cells, which are primarily composed of hydrophilic proteins, or through the intercellular spaces of the stratum corneum, which are composed of lipids (Scheuplein, 1965). Due to their amphiphilic nature, the intercellular hydrolipidic domains constitute a preferential diffusion channel shared by both lipophilic and water-soluble substances. Lipophilic substances diffuse through the hydrophobic regions of the intercellular lipid bilayer. More hydrophilic compounds migrate both through the hydrophilic regions of the intercellular lipid bilayer and via intracellular pathways.

[0014] Lipophilic substances can also be used via the pilosebaceous route through the hair follicle sebaceous gland and / or sweat gland. However, this route remains the least common.

[0015] Alterations to the skin barrier and / or disruption of the continuity of the skin surface can occur in the presence of external aggressors such as irritants (detergents, acids, alkalis, oxidants, reducing agents, concentrated solvents, toxic gases or fumes), mechanical stress (friction, impact, abrasion, surface tearing, projection of dust or particulate matter, shaving or hair removal), thermal or climatic imbalances (cold, dry, high temperature, radiation), or xenobiotics (unwanted microorganisms, allergens) or internal aggressors such as psychological stress.

[0016] This alteration of the skin barrier can manifest as skin discomfort, sensory disturbances, and particularly unpleasant sensations. These discomforts can specifically manifest as tingling, tightness, warmth, and itching. These discomforts are more common in the most exposed areas of the body: the hands, feet, face, and scalp. They can occur in areas subjected to routine or frequently repetitive hygiene procedures, such as shaving, hair removal, washing with toiletries or household products, applying adhesives with bandages or patches, or implanting prostheses; or during physical activity, work-related activities, or simply lifestyle-related activities, and in situations involving the use of clothing, tools, or equipment that generate localized friction.

[0017] Damage to the skin barrier can also promote the appearance of microcracks or microfissures, especially on the hands, feet and lips.

[0018] These uncomfortable skin sensations affect everyone, especially those with sensitive or intolerant skin. The concept of sensitive skin reflects an individual's level of skin sensitivity. While sensitive skin can occur at any age, it is extremely common in infants and the elderly. An infant's skin is about one-fifth the thickness of an adult's skin. Therefore, it is extremely sensitive to chemical, physical, and microbial aggressors, as well as ultraviolet radiation. Meanwhile, as adults age, the skin's barrier function gradually weakens, and metabolic processes slow down. Skin aging gradually leads to lipid deficiency, making it more susceptible to irritation from alkaline substances such as soap.

[0019] Therefore, alterations / weakening of the skin barrier can increase the penetration of exogenous substances (pollutants, irritants, or allergens, also known as allergens), which can sometimes cause irritation or allergic reactions or even oxidative stress.

[0020] One of the reasons for the risk of skin barrier damage is pollution.

[0021] The official definition of pollution is "environmental degradation resulting from the introduction of substances that are not naturally present in the environment into the air, water, or soil." With the continued increase in air pollution, primarily caused by human activities, research has prioritized measures to reduce or control pollutant emissions. The consequences of this air pollution not only have global impacts, such as the greenhouse effect and ozone layer depletion, but also affect the health, well-being, skin, and hair of organisms locally.

[0022] Major pollutants can be categorized into natural and anthropogenic sources. Key pollutants affecting the skin include: solar radiation, polycyclic aromatic hydrocarbons (HAPs), volatile organic compounds (COVs), ozone (O3), nitrogen oxides and sulfur oxides (NOx and SOx), particulate matter (also known as suspended particulates), and tobacco smoke. In most cases, their effects on the skin are amplified when combined with other pollutants and / or solar radiation, particularly UV radiation.

[0023] Air pollution (or atmospheric pollution) is a change in air quality that can be characterized by measuring chemical, biological, or physical pollutants (referred to as "air pollutants"). It can have harmful effects on human health, organisms, and climate. Pollutants typically consist of mixtures of contaminants, such as suspended particulate matter or other substances, whose concentrations and durations of presence are sufficient to produce toxic or ecotoxicological effects. Particulate matter corresponds to a mixture of solid, organic, and mineral particles suspended in the air (EPA - U.S. Environmental Protection Agency). Among other things, it consists of black carbon, benzo[a]pyrene (B(a)P) and other polycyclic aromatic hydrocarbons (HAPs), heavy metals, mineral dust, pollen, mold, and other biological pollutants. They are considered indicators of global pollution (IARC Monograph - Volume 109, 2013). Particulate matter is typically characterized by its size. In fact, their size can determine their deposition area in the respiratory tract (Shah et al., 2013). Particulate matter is often referred to as "PM," with its size appended to PM (PM10: 10 µm; PM2.5: 2.5 µm).

[0024] Suspended particulate matter consists of fine solid particles transported by air or water. The harmful effects are not caused by the particles themselves, but by the molecules adsorbed onto them (benzo[a]pyrene, heavy metals, pesticides, etc.). These particulate substances can produce oxidative stress on the skin, thus contributing at least partially to skin aging. They are suspected of inducing wrinkle formation and the appearance of age spots.

[0025] One of the most notorious air pollutants is benzo[a]pyrene (B(a)P), which is present in high concentrations in particulate matter. It is a concerning persistent air pollutant belonging to the polycyclic aromatic hydrocarbon (HAP) class and is a highly carcinogenic mutagen. It is particularly present in cigarette smoke, exhaust fumes, road vapors, fossil fuel combustion (coal, oil, shale), and the incomplete combustion of organic matter such as in forest fires (INERIS report, 2006). B(a)P undergoes biotransformation through multiple pathways, most of which lead to epoxide intermediates associated with its genotoxicity.

[0026] Furthermore, pollution weakens the skin's protective barrier function by altering the hydrolipidic film. This slows cell renewal, leading to a duller, less firm complexion. Pollution is also known to increase the production of free radicals, causing premature skin aging. Free radicals damage cells and lead to the breakdown of collagen and elastin fibers. Pollutants can also contribute to the development and worsening of skin conditions such as redness, sensitivity, acne, eczema, and psoriasis.

[0027] The transdermal route is one of the main pathways of exposure to contaminants and HAPs (approximately 200 compounds), particularly for non-volatile or low-volatile compounds such as B(a)P. These molecules can cross the lipid barrier of the stratum corneum via simple passive diffusion and, after their metabolism (accompanied by the formation of epoxides), contribute to carcinogenesis. However, when the skin barrier is intact, the level of B(a)P or contaminants absorbed through the skin remains low.

[0028] Therefore, protecting or even improving this skin barrier function is crucial, especially given the increasing pollution in our daily environment, in order to avoid and limit the absorption of pollutants by the skin barrier. Summary of the Invention

[0029] The inventors have surprisingly demonstrated that isocetyl stearyl stearate promotes the enhancement of the epidermal barrier function and prevents its decline, especially under the influence of environmental factors, but also helps to limit or even prevent pollutants from entering the skin, thereby enhancing the skin's protection against pollution.

[0030] In fact, the inventors have demonstrated that isocetyl stearyloxy stearate helps stabilize the intercellular spaces of the stratum corneum, and more specifically, helps to facilitate changes in the state of lipids present in the intercellular spaces, particularly under the influence of temperature.

[0031] To assess changes in the organization of the lipid phase within the intercellular spaces of the stratum corneum, the inventors used attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy to analyze the changes in the fundamental vibrational bands of the aliphatic νCH2 chains of these lipids under temperature, more specifically, the positions of the absorption bands corresponding to the stretching of the CH2 groups. For example, an increase in skin surface temperature caused this band to shift to higher wavenumbers. This shift reflects the fact that lipids in the stratum corneum adopt a less ordered conformation under thermal influence, accompanied by increased mobility of the hydrocarbon chains filling the intercellular spaces. This reflects a decrease in barrier function, allowing exogenous molecules to enter the epidermis more freely.

[0032] It was also demonstrated that isocetyl stearyl oxystearate, with its advantage of enhancing barrier function, can limit the entry of pollutants into the epidermis.

[0033] According to a first aspect, the present invention relates to isocetyl stearyloxy stearate, the use of which for enhancing and / or preventing the reduction of epidermal barrier function.

[0034] This invention also relates to the use of isocetyl stearyl oxystearate in enhancing and / or preventing the decline of epidermal barrier function.

[0035] This invention also relates to the use of isocetyl stearyl oxystearate in the preparation of cosmetic or dermatological compositions for enhancing and / or preventing the reduction of epidermal barrier function.

[0036] The present invention also relates to a method for enhancing and / or preventing a decline in epidermal barrier function, the method comprising administering an effective amount of isocetyl stearyl oxystearate to a person in need.

[0037] According to a second aspect, the present invention relates to a cosmetic or dermatological composition comprising isocetyl stearyloxy stearate and at least one cosmetic or dermatologically acceptable excipient (of the composition according to the invention) for use in enhancing and / or preventing a reduction in epidermal barrier function.

[0038] The present invention also relates to the use of the compositions according to the invention in enhancing and / or preventing a decline in epidermal barrier function.

[0039] The present invention also relates to the use of the compositions according to the invention in the preparation of medicaments for enhancing and / or preventing the reduction of epidermal barrier function.

[0040] The present invention also relates to the use of compositions comprising isocetyl stearyl oxystearate and preferably at least one cosmetic or dermatologically acceptable excipient in the preparation of cosmetic or dermatological compositions for enhancing and / or preventing reduction of epidermal barrier function.

[0041] The present invention also relates to a method for enhancing and / or preventing a decline in epidermal barrier function, the method comprising administering an effective amount of the composition according to the invention to a person in need. Detailed Implementation

[0042] definition In this specification, “approximately” means that the value under discussion may be 10% lower or higher than the specified value, particularly 5%, and particularly 1% higher.

[0043] For the purposes of this invention, "topical application" means application to the skin (including the scalp) and mucous membranes, preferably the skin.

[0044] For the purposes of this invention, “cosmetic or dermatologically acceptable” means a substance that can be used to prepare cosmetic or dermatological compositions, which is generally safe, non-toxic, and neither biologically nor otherwise undesirable, and which can be used for cosmetic or dermatological purposes, particularly by topical application to the skin.

[0045] For the purposes of this invention, "epidermal barrier" refers to the cellular structure of the epidermis, particularly the tissue barrier formed by keratinocytes and the intercellular lipid matrix (lipid phase), namely the stratum corneum (also known as SC).

[0046] For the purposes of this invention, "epidermal barrier function" refers to the protective function of the epidermis, particularly its protective function against external aggressors.

[0047] For the purposes of this invention, "intercellular space" refers to the space containing a lipid phase located between keratinocytes in the stratum corneum.

[0048] For the purposes of this invention, "stabilization of the intercellular space" means a reduction in the instability of the intercellular space, particularly under the influence of environmental factors, and thus has the effect of limiting or preventing the entry of exogenous molecules into the skin, such as chemical or microbial agents, especially irritants, sensitizers (or allergens) or pollutants, which can cause irritation or allergic reactions or oxidative stress in skin that is particularly exposed to environmental factors.

[0049] For the purposes of this invention, "environmental factors" refer to external conditions, such as heat or cold, that cause changes in skin temperature and can destabilize the intercellular spaces of keratinocytes. In a preferred embodiment, heat, such as summer heat or heat caused by sun exposure, can lead to an increase in skin temperature and cause lipids in the intercellular spaces of keratinocytes as defined in this invention to become fluid.

[0050] Isocetyl stearyloxy stearate Isoceridyl stearyloxy stearate is the INCI name of this compound, and its IUPAC name is 14-methylpentadecanyl-12-octadecyloxyoctadecanoate (CAS No.: 97338-28-8), also known as 12-[(1-oxooctadecyl)oxy]octadecanoic acid isochetyl ester. It has the following formula: .

[0051] Within the framework of this invention, isocetyl stearyl stearate can be used to enhance and / or prevent the decline of epidermal barrier function. Barrier function may be reduced under the influence of environmental factors such as cold or heat, especially heat.

[0052] In fact, it has been shown that isocetyl stearyloxy stearate has a stabilizing effect on the intercellular space of keratinocytes.

[0053] Therefore, isocetyl stearyl stearate is particularly effective at allowing exogenous molecules to penetrate the skin. Exogenous molecules can be irritants (hygiene products, solvents, etc.), sensitizers (or allergens) (fragrances, indoor dust, microbial agents, etc.), or even pollutants (polycyclic aromatic hydrocarbons (HAPs)) (e.g., black carbon, benzo[a]pyrene (B(a)P)), volatile organic compounds (COV), ozone (O3), nitrogen oxides (NOx), sulfur oxides (SOx), particulate matter including tobacco smoke, etc.), and more particularly, pollutants. Preferably, the exogenous molecules are pollutants, and more particularly, atmospheric pollutants, such as polycyclic aromatic hydrocarbons (HAPs) (e.g., black carbon, benzo[a]pyrene (B(a)P), volatile organic compounds (COV), ozone (O3), nitrogen oxides (NOx), sulfur oxides (SOx), or particulate matter including tobacco smoke.

[0054] Isocetyl stearyloxy stearate also helps enhance the skin's protection against pollution, more specifically against air pollution, thus acting as an anti-pollution agent.

[0055] Isocetyl stearyl stearate can also be used to prevent irritation and / or allergic reactions, particularly those caused by exogenous molecules such as pollutants, irritants, or sensitizers (also known as allergens). This use is especially beneficial for individuals whose skin is exposed to environmental factors. Isocetyl stearyl stearate can also be used to maintain skin firmness and / or radiance, and / or to prevent skin aging, particularly loss of skin firmness and / or radiance, especially in relation to air pollution.

[0056] Composition Within the scope of this invention, the compositions according to the invention can be used to enhance and / or prevent a decline in epidermal barrier function. Barrier function can be reduced under the influence of environmental factors such as cold or heat, especially heat.

[0057] In fact, the composition according to the present invention has a stabilizing effect on the intercellular spaces of keratinocytes.

[0058] Therefore, the compositions according to the invention are particularly effective at limiting the entry of exogenous molecules into the skin. Exogenous molecules can be, in particular, irritants (hygiene products, solvents, etc.), sensitizers (or allergens) (fragrances, indoor dust, microbial agents, etc.), or even pollutants (polycyclic aromatic hydrocarbons (HAPs)) (e.g., black carbon, benzo[a]pyrene (B(a)P)), volatile organic compounds (COV), ozone (O3), nitrogen oxides (NOx), sulfur oxides (SOx), particulate matter including tobacco smoke, etc.), and more particularly, pollutants. Preferably, the exogenous molecules are pollutants, and more particularly, atmospheric pollutants, such as polycyclic aromatic hydrocarbons (HAPs) (e.g., black carbon, benzo[a]pyrene (B(a)P)), volatile organic compounds (COV), ozone (O3), nitrogen oxides (NOx), sulfur oxides (SOx), or particulate matter including tobacco smoke.

[0059] Therefore, the compositions according to the invention are also able to enhance the skin's protection against pollution, especially air pollution, and thus act as an anti-pollution agent.

[0060] The compositions according to the invention can also be used to prevent irritation and / or allergic reactions, particularly those caused by exogenous molecules such as pollutants, irritants, or allergens (also known as allergens). This use is particularly beneficial for individuals whose skin is exposed to environmental factors.

[0061] The compositions according to the invention can also be used to maintain skin firmness and / or luster, and / or to prevent skin aging, particularly to prevent loss of skin firmness and / or luster, especially in relation to air pollution.

[0062] According to one embodiment, the composition according to the invention contains 0.1% to 10% by weight, particularly 0.2% to 8% by weight, particularly 0.5% to 8% by weight, and more particularly 0.8% to 6% by weight of isocetyl stearyl oxystearate relative to the total weight of the composition.

[0063] According to another embodiment, the composition according to the invention contains 0.1% to 6% by weight, particularly 0.1% to 5% by weight, particularly 0.1% to 4% by weight, and more particularly 0.1% to 3% by weight of isocetyl stearyl oxystearate relative to the total weight of the composition.

[0064] According to another embodiment, the composition according to the invention contains 0.2% to 6% by weight, particularly 0.5% to 5% by weight, particularly 0.6% to 4% by weight, and more particularly 0.8% to 2% by weight of isocetyl stearyl oxystearate relative to the total weight of the composition.

[0065] According to another embodiment, the composition according to the invention contains 0.2% to 1.8% by weight, particularly 0.5% to 1.5% by weight, particularly 0.6% to 1.3% by weight, and more particularly 0.8% to 1.3% by weight of isocetyl stearyl oxy stearate relative to the total weight of the composition.

[0066] Preferably, the composition according to the invention contains about 1% by weight of isocetyl stearyl oxystearate relative to the total weight of the composition.

[0067] According to one embodiment, the composition of the present invention does not contain β-sitosterol. According to one embodiment, the composition of the present invention does not contain tri-2-ethylhexanoate glyceryl ester.

[0068] According to one embodiment, the composition according to the invention does not contain a peptide whose sequence is listed in the GenBank database with accession number WON20281, version WON20281.1, particularly a peptide available in GenBank Release 260 of April 15, 2024, which is also described in US 11,628,133 as corresponding to a peptide having sequence SEQ ID NO: 1.

[0069] According to one embodiment, the composition according to the invention does not contain Lactobacillus Arizonae (… Lactobacillus arizonensis ) on jojoba seeds ( Simmondsia chinensis The products obtained by biotransformation of jojoba seeds, specifically, the compositions of the present invention do not contain the supernatant obtained by biotransformation of jojoba seeds by Lactobacillus Arizonae as described in US 2021 / 0059929.

[0070] According to one embodiment, the composition according to the invention does not contain rose ( French rose Flower extracts, especially rose extract.

[0071] The above implementation schemes are not mutually exclusive and can be combined according to the needs and knowledge of those skilled in the art.

[0072] The compositions according to the invention are advantageously intended for topical application, particularly to the skin. Therefore, they are more specifically in forms suitable for topical application. The compositions according to the invention are particularly suitable for sensitive, fragile, and / or reactive skin.

[0073] Therefore, the compositions according to the invention can exist in forms commonly known for topical application, particularly lotions, emulsions, serums, balms, ointments, masks, creams, dispersions, gels, foams, or sprays. Preferably, it is an emulsion.

[0074] They can also be in solid form, such as stick formulations, or applied to the skin as aerosols. These compositions may contain oily solutions or emulsions, such as oil-in-water emulsions, water-in-oil emulsions, or multiple emulsions.

[0075] The following examples illustrate the invention but do not limit its scope.

[0076] Example Example 1: Evaluation of the effect of temperature on the tissue of lipid matrix To evaluate the tissue changes in the lipid phase of the stratum corneum, the inventors used attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) to analyze the data, specifically the changes in the fundamental vibrational bands of the aliphatic CH2 chains of these lipids under temperature. More specifically, the absorption band corresponding to CH2 stretching was located at wavenumber 2850 cm⁻¹. -1 The location of the stretching peak of the νCH2 bond is characteristic of lipid organization and may be related to barrier function (Boncheva et al., 2008).

[0077] Materials and methods ATR-FTIR measurements were performed on eight human skin donors.

[0078] - Skin explants Human skin samples were obtained from cosmetic surgery. The skin was longitudinally cut to a thickness of approximately 450 µm using an electric dermatologist (Acculan® 3TI, Aesculap®). The resulting skin sample included the entire epidermis and a portion of the dermis.

[0079] - ATR-FTIR Measurement ATR-FTIR spectroscopy (Perkin Elmer) was used to examine the temperature-dependent changes in the fundamental νCH2 vibrational bands of adipose chains. Skin samples were heated at a rate of 1°C / min, and ATR-FTIR spectra were collected at intervals between 28°C and 42°C. Spectra were recorded using TimeBase software (Perkin-Elmer), which allows for kinetic analysis.

[0080] result: The results of ATR-FTIR measurements of human skin explants from eight donors are presented in Table 1.

[0081] [Table 1] SEM: Standard Error of Mean Table 1 shows the effect of temperature on the CH2 bond stretching peak band, a characteristic feature of stratum corneum lipid tissue. Significant differences in lipid tissue were observed between skin at 28°C and 42°C, with the CH2 bond stretching peak band increasing from 2851.06 cm⁻¹ at 28°C. -1 Moved to 2851.87 cm at 42°C -1 (p value < 0.05).

[0082] An increase in skin surface temperature causes this band to shift to higher wavenumbers. This shift reflects the fact that lipids in the stratum corneum adopt a less ordered conformation under the influence of heat, accompanied by increased mobility of hydrocarbon chains filling the intercellular spaces. Therefore, an increase in skin surface temperature from 28°C to 42°C alters lipid organization, thereby impairing the skin barrier function.

[0083] Example 2: Evaluation of the effect of isocetyl stearyloxy stearate on the remodeling of barrier function that restricts the passage of pollutants, particularly benzo[a]pyrene. To evaluate the effects of isocetyl stearyloxy stearate on the tissue and barrier function of lipids in the stratum corneum, an in vitro skin study was conducted on the known contaminant benzo[a]pyrene (B(a)P).

[0084] On the same donor, ATR-FTIR measurements and B(a)P skin penetration were evaluated to link “outside-in” regulation of lipid tissue and skin barrier function when the skin is heated to 42°C.

[0085] First, it has been shown that increasing skin surface temperature from 32°C to 42°C alters lipid organization and impairs skin barrier function, as indicated by increased skin penetration of B(a)P.

[0086] Secondly, the effects of pretreatment with 1% isocetyl stearyloxy stearate on changes in stratum corneum lipid structure and temperature-induced B(a)P skin penetration were evaluated.

[0087] Materials and methods: - Compounds The compounds shown in Table 2 were used in this study.

[0088] [Table 2] *Carbon-14 labeled benzo[a]pyrene - Solubility of B(a)P 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 its solubility in water to be 13.3 µg / L, and experimental data confirm these results at 25°C (May et al., 1983).

[0089] - Guide Conduct transdermal permeation studies according to the following guidelines: ● OECD Guideline 428: "OECD Chemicals Testing Guideline - Skin Absorption: In Vitro Approach" (Guideline 428 - April 13, 2004); ● Guideline SCCS / 0970 / 06: "Basic Standards for In Vitro Evaluation of Skin Absorption of Cosmetic Ingredients" (Updated March 2006).

[0090] - Skin explants Human skin samples were obtained from cosmetic surgery. The skin was longitudinally cut to a thickness of approximately 450 µm using an electric dermatologist (Acculan® 3TI, Aesculap®). The resulting skin sample included the entire epidermis and a portion of the dermis.

[0091] - Experimental research For transdermal absorption studies, two temperatures were used: 32°C and 42°C. Typical skin surface temperature is 32°C. This temperature corresponds to the in vivo skin surface temperature and is commonly used in transdermal absorption studies. At temperatures above 40°C, ATR-FTIR studies observed lipid disordering (altered orthogonal states), which may lead to altered transdermal penetration of pollutants. Based on these results, the second temperature of 42°C was chosen to observe lipid disordering during transdermal absorption experiments.

[0092] Human skin explants were placed in the Franz diffusion cell (1.2 cm). 2The recipient culture medium for each Franz diffusion cell consisted of 0.9% NaCl solution and 4% bovine serum albumin (BSA).

[0093] Human skin explants were then pretreated with either a single carrier (polydimethylsiloxane) (control) or a polydimethylsiloxane solution containing 1% (p / p) isocetyl stearyl oxystearate or compritol. The application volume was 10 µL / cm³. 2 .

[0094] After 30 min, the 0.5% B(a)P acetone solution was added at 10 µL / cm 2 (i.e., 52 µg / cm) 2 ) is applied to the skin explant at a rate of ).

[0095] Twenty-four hours later, the skin surface of the explants was washed twice with water, then twice with acetonitrile, and then twice with half a Whatman™ filter paper disc. The cuticle was then harvested from each explant by sequentially applying 15 DSquame® adhesion sheets.

[0096] The amount of B(a)P was then measured in different compartments: skin surface, stratum corneum, skin (dermis and epidermis), and receiving medium. According to OECD 428 and SCCS / 0970 / 06 guidelines, the total B(a)P recovery rate must be between 85% and 115% of the administered dose.

[0097] It should be noted that skin integrity measurements were performed on each explant prior to the study to verify that transepidermal water loss (PIE) was less than or equal to 13 g / m². 2 / h. This ensures that there are no microscopic damages to the skin explants that are invisible to the naked eye, which could distort the research results.

[0098] Skin permeability studies were conducted on human skin explants from 11 donors. All conditions in Table 3 were evaluated once on one explant from each donor.

[0099] [Table 3] Intergroup comparisons were performed using ANOVA statistical analysis with Graph Pad Prism software.

[0100] result The overall recoveries in all diffusion cells were within acceptable limits, ranging from 90.43% to 95.17% of the applied dose, validating the experiment.

[0101] Table 4 summarizes the percentages found in different compartments.

[0102] [Table 4] *Total percentage found on skin and in the receiving environment ** P < 0.01 relative to 32°C conditions NSS: No statistical significance compared to 32°C conditions. Most of the applied dose of B(a)P is recovered on the skin surface (up to 95.17% of the applied dose).

[0103] At 32°C, the bioavailability of B(a)P (skin + receiver medium) remains low, approximately 2.97% of the administered dose, assuming the skin barrier is intact. Therefore, the skin barrier protects against contaminants (in this case, B(a)P) penetrating the skin layer.

[0104] However, at 42°C, significant amounts of B(a)P were found in the skin (epidermis + dermis) for the polydimethylsiloxane control solution. For compounds with physicochemical properties similar to B(a)P (lipophilic compounds, contaminants), the skin acts as a reservoir, capturing these compounds before they are converted by skin enzymes and potentially released into the bloodstream.

[0105] The bioavailability of B(a)P increased significantly with increasing skin temperature, rising from 2.97% at 32°C to 8.54% of the administered dose at 42°C. These results from the transdermal absorption of B(a)P correlated well with those obtained from ATR-FTIR measurements. Therefore, the increase in temperature reflects changes in lipid structure and thus alters the skin barrier.

[0106] Pretreatment with compritol significantly increased the bioavailability of B(a)P when the skin temperature reached 42°C. Compritol appeared to offer no protection to the skin barrier and therefore could not prevent or limit the penetration of contaminants.

[0107] Surprisingly, however, the inventors were able to observe that, after pretreatment with 1% isocetyl stearyl stearate, the bioavailability of B(a)P did not significantly increase when the skin temperature reached 42°C. Therefore, even when the skin is heated to 42°C, leading to lipid disorder, the absorption of B(a)P does not increase when the same skin is pretreated with isocetyl stearyl stearate.

[0108] The transdermal absorption results of B(a)P obtained 24 hours after topical application correlated well with those obtained from ATR-FTIR measurements. These data indicate that alterations in lipid structure at approximately 42°C induce a weakening of the skin barrier function and increase the bioavailability of compounds such as external contaminants like B(a)P. This suggests that isocetyl stearyl stearate significantly improves barrier function. B(a)P skin penetration studies demonstrate that pretreatment with 1% isocetyl stearyl stearate helps stabilize lipid structure and improve barrier function. Isocetyl stearyl stearate also acts as an antifouling agent by limiting the passage of contaminants across the skin barrier.

[0109] References ● IARC Monograph - Volume 109, 2013; ● INERIS Report, 2006; ● OECD Guideline 428: "OECD Chemicals Testing Guideline - Skin Absorption: In Vitro Approach" (Guideline 428 - April 13, 2004); ● SCCS / 0970 / 06 Guideline: "Basic Standards for In Vitro Evaluation of Skin Absorption of Cosmetic Ingredients" (Updated March 2006). ● Blank, 1953, Journal of Investigative Dermatology, 259-271; ● Boncheva et al., 2008, Biochimica and Biophysica Acta, 1778, 1344-1355; ● Bouwstra et al., 2008, International Journal of Cosmetic Science, 30(5), 388-390; ● de Jager et al., 2005, Journal of Lipid Research, 46, 2649-2656; ● May et al., 1983, Journal Chemistry Reference Data, 28, 197-200; ● Schaefer and Redelmeier, 2011, Contact Dermatitis, Chapter 11, entitled “Skinpenetration”, ISBN: 978-3-642-03826-6; ● Shah et al., 2013, Lancet 382, ​​1039-1048; ● Scheuplein, 1965, Journal of Investigative Dermatology, 45(5), 334 - 346; ● van Smeden et al., 2014, Biochimica and Biophysica Acta, 1841, 295 - 313.

Claims

1. Isoceridyl stearyl oxystearate, for use in enhancing and / or preventing the reduction of epidermal barrier function to improve the skin's protection against pollution.

2. The isocetyl stearyl oxystearate for use according to claim 1, which is used to restrict the entry of exogenous molecules into the skin, said exogenous molecules being pollutants.

3. Isoceridyl stearyl oxystearate, for the purpose of preventing irritation and / or allergic reactions, particularly irritation and / or allergic reactions caused by exogenous molecules, preferably contaminants.

4. A cosmetic or dermatological composition comprising isocetyl stearyloxy stearate and at least one cosmetic or dermatologically acceptable excipient for use in enhancing and / or preventing a reduction in epidermal barrier function to improve the skin’s protection against pollution.

5. The composition for use according to claim 4, wherein it is used to restrict the entry of exogenous molecules into the skin, said exogenous molecules being pollutants.

6. A cosmetic or dermatological composition comprising isocetyl stearyloxy stearate and at least one cosmetic or dermatologically acceptable excipient for the purpose of preventing irritation and / or allergic reactions, particularly irritation and / or allergic reactions caused by exogenous molecules, preferably contaminants.

7. The composition for use according to any one of claims 4 to 6, characterized in that, The composition comprises 0.1% to 10% by weight of isocetyl stearyl oxystearate relative to the total weight of the composition.

8. The composition for use according to any one of claims 4 to 7, characterized in that, The composition comprises, relative to the total weight of the composition, 0.2% to 1.8% by weight, preferably 0.5% to 1.5% by weight, 0.6% to 1.3% by weight, or 0.8% to 1.3% by weight of isocetyl stearyl oxystearate.

9. The composition for use according to any one of claims 4 to 8, characterized in that, It is a form suitable for local application.

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