Isocetyl stearoyl stearate for strengthening the epidermal barrier function

Abstract

The present invention relates to isocetyl stearoyl stearate for use in enhancing and / or preventing the deterioration of the epidermal barrier function, particularly for enhancing protection of the skin against contamination. The present invention relates to a cosmetic or dermatological composition comprising isocetyl stearoyl stearate and at least one cosmetic or dermatologically acceptable excipient for use in enhancing and / or preventing the deterioration of the epidermal barrier function, particularly for enhancing protection of the skin against contamination.

Description

Technical Field

[0001] The present invention relates to the use of isocetyl stearoyl stearate and / or the use of a composition comprising isocetyl stearoyl stearate for enhancing the epidermal barrier function and / or preventing the reduction of the epidermal barrier function, and more particularly for enhancing the protection of the skin against contamination, especially air pollution.

Background Art

[0002] The skin is composed of various layers and forms an important barrier of the body against the external environment. Since this barrier protects the body from external attacks, especially chemical, mechanical, or infectious attacks, many defense reactions against environmental factors and / or xenobiotics occur at this level.

[0003] [[ID=十六]]The skin consists of three main parts: the outer layer (epidermis); the inner layer (dermis); and the deeper layer (subcutaneous tissue), which influence each other. The human epidermis is composed of 4 to 5 distinct layers (depending on the anatomical site) and consists of four cell types: the most numerous keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Each of these cell types contributes to the essential role that the skin plays in the body, particularly the role of protecting the body from external attacks, through its specific function. This property is called the barrier function.

[0004] Epidermal cells proliferate in the basal layer, the deepest layer, and differentiate during their migration to the upper layers, forming a continuous chain of layers: the stratum spinosum, consisting of several layers of polyhedral cells arranged on the germinal layer; the granular layer, consisting of flattened cells containing distinct cytoplasmic inclusions called keratohyalin granules; and finally, the stratum corneum, the outermost layer of the epidermis. The stratum corneum consists of 10 to 30 layers of keratinocytes, the final stage of differentiation, and are called corneocytes. Corneocytes, the components of the stratum corneum, are dead, flat cells containing water and keratin. The structure of the stratum corneum has traditionally been likened to a brick wall, with "bricks" representing corneocytes. The spaces between corneocytes are filled with organized lipids, forming a hydrophobic "cement" around the corneocytes (partially ensuring the impermeability of the stratum corneum). During the keratinization process, the spaces between corneocytes are filled with lipids. These lipids are organized into layers and make up about 15% of the dry weight of the stratum corneum.

[0005] The lipid composition of the stratum corneum is very different from that of biological membranes. It contains very few phospholipids and is mainly composed of ceramide (50% by mass), cholesterol (25%), and free fatty acids (10-20%). These lipids form the intracellular cement of the stratum corneum (van Smeden et al., 2014).

[0006] In the 1990s, transmission electron microscopy revealed the layered structure of intercellular lipids in keratinocytes, showing that transparent bands and electron-dense bands alternately appear parallel to the keratinocyte surface. Lipids thus form multilayered structures, aligned perpendicular to the keratinocyte surface and parallel to one another. The electron-dense bands correspond to the arrangement of polar head groups of ceramides and hydroxyl groups of fatty acids and cholesterol. The light bands correspond to the nonpolar hydrocarbon chains of these lipids, aligned opposite each other. In vitro experiments demonstrated that only the specific lipid composition of the stratum corneum allows for this particular lipid layer arrangement (de Jager et al., 2005).

[0007] The supramolecular organization of intercellular spaces in the stratum corneum plays a crucial role in establishing the physicochemical properties of the stratum corneum and, consequently, maintaining the physiological water gradient. The structure of these lipid bilayers exhibits either a specific hexagonal (gelled state) or orthorhombic (a crystalline system where the unit cell is a rectangular parallelepiped) configuration, with the latter being dominant (Bouwstra et al., 2008). The orthorhombic state represents the densest conformation, and a balance between these two states is necessary for optimal barrier properties. Imbalances in the proportions of the three lipid groups in the stratum corneum, or external stresses (heat or cold), alter the orthorhombic and hexagonal states, and thus lead to changes in barrier function.

[0008] This lipid structure, along with the aggregation of epidermal cells, plays a role in the skin's water exchange and water loss (transepidermal water loss) and its protective or barrier function against external attacks (xenobiotics, pathogens, UV). For a long time, the stratum corneum was thought to be a monolayer of dead cells with no function. In reality, it is metabolically active and is responsible for a large part of the epidermal barrier function.

[0009] However, this barrier is not absolute. In fact, the skin is involved in regulating the body's overall homeostasis by controlling the loss of water and electrolytes (Blank, 1953). It is permeable to small molecules (less than 500 Daltons), but only to varying degrees. This is mainly related to the physiological state of the skin and the physicochemical properties of compounds that the skin is thought to restrict the penetration of (Schaefer and Redelmeier, 2010).

[0010] The stratum corneum, due to its structure and composition, constitutes the main barrier.

[0011] Anatomically, there are two different pathways for the passage of substances: one is the transepidermal pathway, and the other is the transfollicular pathway.

[0012] In the transepidermal pathway, molecular diffusion occurs primarily through stratum corneum cells, which are composed mainly 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 domain constitutes a preferential diffusion channel for both lipids and water-soluble substances. Lipophilic substances diffuse through the hydrophobic regions of the intercellular lipid bilayer. More hydrophilic compounds move, on the one hand, through the hydrophilic regions of the intercellular lipid bilayer, and on the other hand, through intracellular pathways.

[0013] Lipophilic substances can also utilize the transfollicular pathway via the sebaceous glands and / or sweat glands. However, this pathway remains relatively rare.

[0014] Alterations in the skin barrier and / or disruption of the continuity of the skin surface can occur in the presence of external attacks such as irritants (surfactants, acids, bases, oxidizing agents, reducing agents, concentrated solvents, toxic gases or fumes), mechanical stress (friction, impact, abrasion, surface cracking, dust or particulate matter projection, shaving or hair removal), or xenobiotics (unwanted microorganisms, allergens), or internal attacks such as psychological stress.

[0015] This alteration of the skin barrier can manifest as skin discomfort, sensory disturbances, and particularly unpleasant sensations. This skin discomfort may manifest as tingling, tightness, warmth, and itching. These skin discomforts often occur on the most exposed parts of the body, namely the hands, feet, face, and scalp. They may occur in areas exposed to certain daily or frequently repeated hygiene practices, such as shaving, hair removal, washing with toiletries or household products, application of adhesives with bandages or patches, or fitting prosthetics, or during sports activities, work-related activities, or simply lifestyle-related activities, and with the use of clothing, tools, or devices that cause localized friction.

[0016] Damage to the skin barrier can also promote the appearance of microcracks or microfissures, particularly on the hands, feet, and lips.

[0017] These skin discomforts affect everyone, but especially those with sensitive or intolerant skin. The concept of sensitive skin reflects the level of sensitivity of an individual's skin. Sensitive skin can develop at any age, but it is much more common in infants and the elderly. A baby's skin is about one-fifth the thickness of an adult's. As a result, a baby's skin is very sensitive to chemical, physical, and microbial attacks, as well as ultraviolet radiation. On the other hand, the barrier function of adult skin gradually declines with age, linked to a slowdown in metabolic processes. Skin aging gradually leads to a deficiency of lipids, making it more susceptible to irritation from alkaline substances such as soap.

[0018] Therefore, changes / weakening of the skin barrier increase the penetration of exogenous molecules (polluting agents, irritants, or allergens), which can sometimes cause irritation or allergic reactions, and even oxidative stress.

[0019] One of the causes of risk to skin barrier damage is contamination.

[0020] The official definition of pollution is "environmental degradation caused by the introduction of substances not naturally present in the environment into the atmosphere, water, or soil." With air pollution, primarily caused by human activities, continuing to increase, measures have been implemented to prioritize research focused on reducing or limiting emissions of polluting gases. The effects of this air pollution extend beyond global impacts such as the greenhouse effect and ozone depletion to local impacts on the health, well-being, skin, and hair of living organisms.

[0021] Major pollutants have both natural and anthropogenic origins. Major pollutants that affect the skin include: solar radiation, polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), ozone (O3), nitrogen oxides and sulfur oxides (NOx and SOx), particulate matter (also known as suspended particulate matter), and cigarette smoke. Often, the effects of these pollutants on the skin are amplified when combined with other pollutants and / or solar radiation, especially UV radiation.

[0022] Air pollution (or atmospheric pollution) is a change in air quality that can be characterized by the measurement of chemical, biological, or physical pollutants (called “air pollutants”), which can have harmful effects on human health, living organisms, and the climate. Pollutants generally consist of a cocktail of pollutants, such as suspended particulate matter or other substances whose concentration and duration of presence are sufficient to produce toxic or ecotoxic effects. Particulate matter refers to a mixture of solid, organic, and mineral particulate matter suspended in the atmosphere (EPA). It consists, among other things, of black carbon, benzo[a]pyrene (B(a)P) and other polycyclic aromatic hydrocarbons (PAHs), heavy metals, mineral dust, pollen, mold, and other biological pollutants. These are considered indicators of global pollution (IARC Monograph - Vol. 109, 2013). Particulate matter is, in most cases, characterized by its size. In fact, their size can determine their deposition zone in the respiratory tract (Shah et al., 2013). Particulate matter is generally called PM, and PM is often prefixed with its size (PM10: 10 μm, PM2.5: 2.5 μm).

[0023] Suspended particulate matter consists of fine solid particulate matter carried by air or water. It is not the particulate matter itself that causes harmful effects, but rather the molecules adsorbed onto them (such as benzo[a]pyrene, heavy metals, pesticides, etc.). Since these particulate matters can generate oxidative stress on the skin, they are at least partially responsible for skin aging. They are thought to induce the formation of wrinkles and the appearance of spots.

[0024] One of the most well-known air pollutants is benzo[a]pyrene (B(a)P), which is found in significant amounts in particulate matter. This is a concerning persistent air pollutant belonging to polycyclic aromatic hydrocarbons (PAHs) and is a mutagen showing high carcinogenicity. It is particularly found in incomplete combustion of organic substances such as tobacco smoke, exhaust gas, road surface vapor, combustion of fossil fuels (coal, oil, shale), and forest fires (INERIS report, 2006). B(a)P undergoes biotransformation through multiple pathways, most of which result in epoxide intermediates involved in genotoxicity.

[0025] Furthermore, pollution weakens the skin's protective barrier function by changing the hydro-lipid membrane. As a result, the cell regeneration rate slows down, the skin color fades, and the skin becomes dull and lacks firmness. Pollution is also known to prematurely age the skin by increasing the production of free radicals, which damage cells and lead to the degradation of collagen and elastin fibers. Pollutants may also contribute to the onset and exacerbation of skin diseases such as redness, allergies, acne, eczema, and psoriasis. <000008​​​​​​Therefore, since pollution is increasingly present in our daily environment, it is essential to maintain and further improve this skin barrier function in order to avoid and limit the absorption of pollutants by the skin barrier. Summary of the Invention

[0028] The inventors have surprisingly demonstrated that isocetyl stearoyl stearate promotes the strengthening of the epidermal barrier function and particularly prevents the decline of this epidermal barrier function under the influence of environmental factors, while also helping to limit or even prevent the passage of pollutants through the skin, thereby enhancing the protection of the skin against pollution.

[0029] In fact, the inventors have demonstrated that isocetyl stearoyl stearate helps to stabilize the state change of the lipids present in the intercellular spaces of the keratinocytes in the stratum corneum, more specifically the state change being observed particularly under the influence of temperature.

[0030] To evaluate the changes in the organization of the lipid phase in the intercellular spaces of the keratinocytes in the stratum corneum, the inventors used attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy to analyze the variations in the temperature of the fundamental vibration band of the aliphatic νCH2 chains of these lipids, more specifically the absorption bands corresponding to the stretching of the CH2 groups. For example, an increase in the skin surface temperature shifts this band to a higher wavenumber. This shift reflects the fact that the lipids in the stratum corneum take on a more disordered conformation with an increase in the fluidity of the hydrocarbon chains filling the intercellular spaces under the influence of heat. This reflects a decline in the barrier function and allows for a more free passage of exogenous molecules into the epidermis.

[0031] Isocetyl stearoyl stearate has also been shown to be able to limit the passage of pollutants through the epidermis by virtue of its function of strengthening the barrier function.

[0032] According to a first aspect, the present invention relates to isocetyl stearoyl stearate for use in enhancing the epidermal barrier function and / or preventing the decline of the epidermal barrier function.

[0033] The present invention also relates to the use of isocetyl stearoyl stearate in enhancing the epidermal barrier function and / or preventing the deterioration of the epidermal barrier function.

[0034] The present invention also relates to the use of isocetyl stearoyl stearate for the preparation of cosmetic or dermatological compositions for enhancing and / or preventing a decrease in epidermal barrier function.

[0035] The present invention also relates to a method for enhancing and / or preventing a decline in epidermal barrier function, comprising administering an effective amount of isocetylstearoylstearate to a person in need.

[0036] According to a second aspect, the present invention relates to a cosmetic or dermatological composition for use in enhancing and / or preventing the deterioration of the epidermal barrier function, comprising isocetyl stearoyl stearate together with at least one cosmetic or dermatologically acceptable excipient (a composition according to the present invention).

[0037] The present invention also relates to the use of compositions according to the present invention in enhancing the epidermal barrier function and / or preventing a decrease in the epidermal barrier function.

[0038] The present invention also relates to the use of compositions according to the present invention for preparing agents for enhancing and / or preventing the deterioration of the epidermal barrier function.

[0039] The present invention also relates to the use of compositions comprising isocetyl stearoyl stearate and preferably at least one cosmetic or dermatologically acceptable excipient for preparing cosmetic or dermatological compositions for enhancing and / or preventing impairment of the epidermal barrier function.

[0040] The present invention also relates to a method for enhancing and / or preventing the deterioration of the epidermal barrier function, which includes administering an effective amount of the composition according to the present invention to a person who requires it. [Modes for carrying out the invention]

[0041] definition In this specification, "about" means that the value may be 10% lower or higher than the stated value, and may be 5% higher in particular, and especially 1% higher.

[0042] In the present invention, "topical application" means application to the skin and mucous membranes (including the scalp), preferably to the skin.

[0043] In the present invention, "cosmetic or dermatologically acceptable" means that a substance is useful in the preparation of cosmetic or dermatological compositions, is generally safe, non-toxic, and is biologically and otherwise undesirable, and is particularly acceptable for cosmetic or dermatological use by topical application to the skin.

[0044] In the present invention, "epidermal barrier" means the tissue barrier formed by the cellular structure of the epidermis, particularly keratinocytes and intercellular lipid cement (lipid phase), i.e., the stratum corneum (also called SC).

[0045] In this invention, "epidermal barrier function" specifically refers to the protective function of the epidermis against external attacks.

[0046] In this invention, "intercorneocyte spaces" refers to the spaces containing the lipid phase located between keratinocytes in the stratum corneum.

[0047] In the present invention, "stabilization of the intercellular space of keratinocytes" means a reduction in the destabilization of the intercellular space of keratinocytes, particularly under the action of environmental factors, and therefore has the effect of limiting or blocking the passage of exogenous molecules into the skin, such as chemical agents or microbial agents, particularly irritants, allergens, or contaminants that can cause irritation and allergic reactions or oxidative stress in skin exposed to environmental factors.

[0048] In the present invention, "environmental factors" refer to external conditions such as heat or cold that induce fluctuations in skin temperature that can destabilize the intercellular spaces of keratinocytes. In a preferred embodiment, heat, such as that experienced during the summer or due to sun exposure, induces an increase in skin temperature, causing the lipids in the intercellular spaces of keratinocytes to become fluid, as defined in the present invention.

[0049] Isocetyl stearoyl stearate Isocetyl stearoyl stearate has the IUPAC name 14-methylpentadecyl 12-octadecanoyloxyoctadecanoate (CAS number 97338-28-8) and the INCI name, and is also known as isohexadecyl 12-[(1-oxooctadecyl)oxy]octadecanoate. It has the following chemical formula: TIFF2026529132000001.tif31157

[0050] Within the framework of the present invention, isocetyl stearoyl stearate is useful for strengthening and / or preventing the deterioration of the epidermal barrier function. The barrier function can be impaired under the influence of environmental factors such as cold or heat, especially heat.

[0051] In fact, isocetyl stearoyl stearate has been shown to have a stabilizing effect on the intercellular space of keratinocytes.

[0052] Therefore, isocetyl stearoyl stearate can particularly restrict the passage of exogenous molecules into the skin. Exogenous molecules may be irritants (such as sanitary products and solvents), allergens (or allergens) (such as perfumes, house dust, and microbial agents), or pollutants (polycyclic aromatic hydrocarbons (PAHs)) (e.g., black carbon, benzo[a]pyrene (B(a)P)), volatile organic compounds (VOCs), ozone (O3), nitrogen oxides (NOx), sulfur oxides (SOx), and suspended particulate matter including cigarette smoke), more specifically, pollutants. Preferably, exogenous molecules are pollutants, and more specifically, air pollutants such as polycyclic aromatic hydrocarbons (PAHs) (e.g., black carbon, benzo[a]pyrene (B(a)P)), volatile organic compounds (VOCs), ozone (O3), nitrogen oxides (NOx), sulfur oxides (SOx), or suspended particulate matter including cigarette smoke.

[0053] Isocetyl stearoyl stearate is also useful in enhancing skin protection against pollution, more specifically air pollution, and therefore acts as an anti-pollution agent.

[0054] Isocetyl stearoyl stearate is also useful in preventing irritation and / or allergic reactions, particularly those caused by exogenous molecules such as pollutants, irritants, or allergens. This use is especially beneficial for people whose skin is exposed to environmental factors. Isocetyl stearoyl stearate is also useful in maintaining skin firmness and / or radiance and / or preventing skin aging, particularly in preventing the loss of skin firmness and / or radiance associated with air pollution.

[0055] composition Within the scope of the present invention, the compositions according to the present invention are useful for strengthening the epidermal barrier function and / or preventing the deterioration of the epidermal barrier function. The barrier function may be reduced under the influence of environmental factors such as cold or heat (or heat), especially heat.

[0056] In fact, the composition according to the present invention has a stabilizing effect on the intercellular space of keratinocytes.

[0057] Therefore, the compositions according to the present invention can, in particular, restrict the passage of exogenous molecules to the skin. Exogenous molecules may be, in particular, irritants (such as sanitary products and solvents), allergens (or allergens) (such as perfumes, house dust and microbial agents), or pollutants (polycyclic aromatic hydrocarbons (PAHs)) (e.g., black carbon, benzo[a]pyrene (B(a)P)), volatile organic compounds (VOCs), ozone (O3), nitrogen oxides (NOx), sulfur oxides (SOx), and suspended particulate matter including cigarette smoke), more specifically, pollutants. Preferably, the exogenous molecules are pollutants, more specifically, air pollutants such as polycyclic aromatic hydrocarbons (PAHs) (e.g., black carbon, benzo[a]pyrene (B(a)P)), volatile organic compounds (VOCs), ozone (O3), nitrogen oxides (NOx), sulfur oxides (SOx), or suspended particulate matter including cigarette smoke.

[0058] Therefore, the compositions according to the present invention can enhance the protection of the skin against pollution, more specifically air pollution, and thus can act as anti-pollution agents.

[0059] The compositions of the present invention are also useful in preventing irritation and / or allergic reactions, particularly those caused by exogenous molecules such as contaminants, irritants, or allergens (also known as allergens). This use is especially beneficial for people whose skin is exposed to environmental factors.

[0060] The compositions according to the present invention are also useful for maintaining skin firmness and / or radiance and / or preventing skin aging, particularly for preventing the loss of skin firmness and / or radiance associated with air pollution.

[0061] According to one embodiment, the composition according to the present invention contains isocetyl stearoyl stearate in an amount of 0.1% to 10% by weight, particularly 0.2% to 8% by weight, particularly 0.5% to 8% by weight, and more specifically 0.8% to 6% by weight, based on the total weight of the composition.

[0062] According to other embodiments, the composition according to the present invention contains isocetyl stearoyl stearate in an amount of 0.1% to 6% by weight, particularly 0.1% to 5% by weight, particularly 0.1% to 4% by weight, and more specifically 0.1% to 3% by weight, based on the total weight of the composition.

[0063] According to other embodiments, the composition according to the present invention contains isocetyl stearoyl stearate in an amount of 0.2% to 6% by weight, particularly 0.5% to 5% by weight, particularly 0.6% to 4% by weight, and more specifically 0.8% to 2% by weight, based on the total weight of the composition.

[0064] According to other embodiments, the composition according to the present invention contains isocetyl stearoyl stearate in an amount of 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 specifically 0.8% to 1.3% by weight, based on the total weight of the composition.

[0065] Preferably, the composition according to the present invention contains about 1% by weight of isocetyl stearoyl stearate based on the total weight of the composition.

[0066] 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 glyceryl tri-2-ethylhexanoate.

[0067] According to one embodiment, the composition according to the present invention does not contain a peptide having a sequence registered in the GenBank database with access number WON20281, version WON20281.1, and in particular available in GenBank release 260 dated April 15, 2024, which is described in U.S. Patent No. 11,628,133 as the peptide having Sequence ID No. 1.

[0068] According to one embodiment, the composition according to the present invention does not contain bioconversion products from Lactobacillus arizonensis derived from Simmondsia chinensis, and in particular, the composition according to the present invention does not contain the supernatant obtained by bioconverting Simmondsia chinensis with Lactobacillus arizonensis, as described in U.S. Patent Application Publication No. 2021 / 0059929.

[0069] According to one embodiment, the composition according to the present invention does not contain Rosa gallica flower extract, particularly rose extract.

[0070] The embodiments described above are not mutually exclusive and can be combined according to the needs and knowledge of those skilled in the art.

[0071] The compositions according to the present 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 present invention can be applied to sensitive, fragile, and / or reactive skin in particular.

[0072] Therefore, the compositions according to the present invention can be provided in forms commonly known for topical administration, particularly in the form of lotions, milks, emulsions, serums, balms, ointments, masks, creams, dispersions, gels, foams, or sprays. Preferably, the form is a milk.

[0073] They may also be in solid form, such as sticks, 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.

[0074] The following examples illustrate the present invention without limiting its scope.

[0075] Example 1: Evaluation of the effect of temperature on lipid matrix organization To evaluate the changes in the organization of the lipid phase of the stratum corneum, the inventors used attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) to analyze the temperature-dependent fluctuations of the fundamental vibrational bands of the aliphatic CH2 chains of these lipids. More specifically, the position of the absorption band corresponding to the stretching of CH2 was at wavenumber 2850 cm⁻¹. -1 It is located in the vicinity. The position of the νCH2 binding stretching peak band is characteristic of lipid tissue and may correlate with barrier function (Boncheva et al., 2008).

[0076] material and method: ATR-FTIR measurements were performed on eight human skin donors. - Skin explants Human skin samples were obtained from cosmetic surgery. Using an electric dermatome (Acculan® 3TI, Aesculap®), the skin was longitudinally sectioned into approximately 450 μm thick sections. The resulting skin samples included the entire epidermis and a portion of the dermis.

[0077] - ATR-FTIR measurement The temperature dependence of the fundamental νCH2 vibrational band in aliphatic chains was investigated using ATR-FTIR spectroscopy (Perkin Elmer). Skin samples were heated at a rate 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) to enable kinetic analysis.

[0078] result: Table 1 shows the results of ATR-FTIR measurements performed on human skin explants from eight donors.

[0079] [Table 1]

[0080] Table 1 shows the effect of temperature on the CH2 binding stretch peak band, which is a characteristic of the lipid tissue of the stratum corneum. A significant difference in lipid composition was observed between skin at 28°C and skin at 42°C, and the CH2 binding stretch peak band was 2851.06 cm- at 28°C. 1 From 42℃ to 2851.87cm- 1 It shifted to (p-value < 0.05).

[0081] An increase in skin surface temperature shifts this band to a higher wavenumber. This shift reflects the fact that under the influence of heat, the lipids of the stratum corneum adopt a less orderly structure, and the fluidity of the hydrocarbon chains filling the intercellular spaces of the keratinocytes increases. Therefore, when the skin surface temperature rises from 28°C to 42°C, the lipid composition changes, and as a result, the skin's barrier function is impaired.

[0082] Example 2: Evaluation of the effect of isocetyl stearoyl stearate on the reorganization of barrier function to restrict the passage of contaminants, particularly benzo[a]pyrene. To evaluate the effects of isocetyl stearoyl stearate on lipid organization and barrier function in the stratum corneum, we developed and performed an in vitro skin penetration test for benzo[a]pyrene (B(a)P), a known contaminant.

[0083] For the same donor, ATR-FTIR measurements and B(a)P skin penetration were evaluated, and the relationship between lipid organization and "outside-to-inside" regulation of skin barrier function when the skin was heated to 42°C was investigated.

[0084] Firstly, it was shown that when the temperature at the skin surface rises from 32°C to 42°C, as indicated by the increased skin penetration of B(a)P, the lipid composition changes and the skin barrier function is impaired.

[0085] Next, the effects of pretreatment with a 1% concentration of isocetyl stearoyl stearate were evaluated on changes in the lipid structure of the stratum corneum caused by temperature rise and on the skin penetration of B(a)P.

[0086] material and method: - compound The compounds shown in Table 2 were used in this study.

[0087] [Table 2]

[0088] - 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 a solubility of 13.3 μg / L in water, and experimental data confirm these results at 25°C (May et al., 1983).

[0089] - Guidelines The transdermal penetration test was conducted according to the following guidelines. OECD Guideline 428: "OECD Guidelines for Testing Chemical Substances - Skin Absorption: In vitro Methods" (Guideline 428 - April 13, 2004); Guideline SCCS / 0970 / 06: "Basic Standards for In vitro Evaluation of Transdermal Absorption of Cosmetic Ingredients" (Updated March 2006).

[0090] - Skin explants Human skin samples were obtained from cosmetic surgery. Using an electrodermatome (Acculan®3 TI, Aesculap®), the skin was longitudinally sectioned into approximately 450 μm thick sections. The resulting skin samples included the entire epidermis and a portion of the dermis.

[0091] - Experimental research In the transdermal absorption test, two temperatures, 32°C and 42°C, were used. The typical skin surface temperature is 32°C. This temperature corresponds to the in vivo skin surface temperature and is commonly used in transdermal absorption tests. At temperatures above 40°C, ATR-FTIR studies have shown lipid degradation (changes in orthorhombic crystal state), which may lead to changes in the transdermal permeability of pollutants. Based on these results, a second temperature of 42°C was selected to observe lipid degradation during the transdermal absorption experiment.

[0092] Human skin explants in Franz diffusion cells (1.2 cm 2 The receptor medium for each Franz diffusion cell was composed of a 0.9% NaCl solution and 4% bovine serum albumin (BSA).

[0093] Next, human skin explants were pretreated with the base alone (dimethicone) (control) or with a dimethicone solution containing 1% (w / w) isocetyl stearoyl stearate or complitol. The applied volume was 10 μL / cm³. 2 That is the case.

[0094] After 30 minutes, add 10 μl / cm³ of 0.5% B(a)P solution in acetone. 2 (That is, 52 μg / cm³) 2 It was applied to the skin explant at the following speed:

[0095] After 24 hours, the surface of the skin explants was washed twice with water, then twice with acetonitrile, and then twice with half a Whatman® filter paper disc. Subsequently, the stratum corneum was collected from each explant by applying D-Squame® adhesive 15 times consecutively.

[0096] Next, the amount of B(a)P was measured in different compartments: skin surface, stratum corneum, skin (dermis and epidermis), and the receiving medium. According to OECD428 and SCCS / 0970 / 06 guidelines, the total B(a)P recovery rate should be between 85% and 115% of the applied dose.

[0097] Before conducting the test, skin integrity measurements were performed on each explant, and the transepidermal water loss (TEWL) was 13 g / m². 2 It should be noted that the value should be less than / h. This ensures that no microscopic lesions, invisible to the naked eye, develop in the skin explant, which could potentially distort the study results.

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

[0099] [Table 3]

[0100] result The total recovery rate of all diffusion cells was within the acceptable range of 90.43% to 95.17% of the administered dose, thus validating the experiment. The percentages approved in each section are summarized in Table 4.

[0101] [Table 4]

[0102] The majority of the B(a)P dose was recovered on the skin surface (up to 95.17% of the dose).

[0103] At 32°C, the bioavailability of B(a)P (skin + receptor medium) is low, approximately 2.97% of the administered dose, assuming the skin barrier is intact. Therefore, the skin barrier plays a protective role by preventing contaminants (in this case, B(a)P) from penetrating the skin layers.

[0104] However, at 42°C, a significant amount of B(a)P was detected in the skin (epidermis + dermis) of the dimethicone 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 conversion by skin enzymes and their potential release into the bloodstream occur.

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

[0106] After pretreatment with Complitol, the bioavailability of B(a)P significantly increased when the skin temperature rose to 42°C. Complitol does not appear to have any protective effect on the skin barrier and therefore does not prevent or limit the penetration of contaminants.

[0107] However, surprisingly, the inventors were able to observe that the bioavailability of B(a)P did not significantly increase when the skin temperature reached 42°C after pretreatment with 1% isocetyl stearoyl stearate. Therefore, even if the skin is heated to 42°C and lipid breakdown occurs, the absorption of B(a)P does not increase at all when the same skin is pretreated with isocetyl stearoyl stearate.

[0108] The results obtained regarding the transdermal absorption of B(a)P 24 hours after topical application correlate well with the results obtained from ATR-FTIR measurements. These data showed that changes in lipid tissue at approximately 42°C induce a decrease in skin barrier function and increase the bioavailability of compounds such as external contaminants like B(a)P. This demonstrates that the use of isocetyl stearoyl stearate significantly improves barrier function. Pretreatment with 1% isocetyl stearoyl stearate helps stabilize lipid tissue and improves barrier function, as shown by the B(a)P skin penetration test. The use of isocetyl stearoyl stearate also acts as an anti-contamination agent by limiting the passage of contaminants through the skin barrier.

[0109] References IARC Monographs - Volume 109, 2013; INERIS report, 2006; OECD Guideline 428: "OECD Guidelines for Testing Chemical Substances - Skin Absorption: In Vitro Methods" (Guideline 428 - April 13, 2004); SCCS / 0970 / 06 Guidelines: "Basic Criteria for In vitro Evaluation of Transdermal 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; References: Vol.1, p.1, p.2, p.3 Schaefer and Redelmeier, 2011, Contact Dermatitis, Chapter 11, "Skin Penetration," ISBN: 978-3-642-03826-6; Shah et al., 2013, The 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. Isocetyl stearoyl stearate, used to enhance the epidermal barrier function and / or prevent its deterioration, thereby increasing the skin's protection against contamination.

2. The isocetyl stearoyl stearate according to claim 1, used to restrict the passage of exogenous molecules into the skin, wherein the exogenous molecules are contaminants.

3. It is used in particular to prevent irritation and / or allergic reactions caused by exogenous molecules, where the exogenous molecule is preferably a contaminant, such as isocetyl stearoyl stearate.

4. A cosmetic or dermatological composition comprising isocetyl stearoyl stearate and at least one cosmetic or dermatologically acceptable excipient, used to enhance the epidermal barrier function and / or prevent the deterioration of the epidermal barrier function, thereby enhancing protection of the skin against contamination.

5. The composition according to claim 4, used to restrict the passage of exogenous molecules into the skin, wherein the exogenous molecules are contaminants.

6. A cosmetic or dermatological composition comprising isocetyl stearoyl stearate and at least one cosmetic or dermatologically acceptable excipient, used particularly to prevent irritation and / or allergic reactions caused by exogenous molecules, wherein the exogenous molecules are preferably contaminants.

7. The composition according to any one of claims 4 to 6, characterized by containing 0.1% to 10% by weight of isocetyl stearoyl stearate based on the total weight of the composition.

8. The composition according to any one of claims 4 to 7, characterized in that it contains isocetyl stearoyl stearate in an amount of 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, based on the total weight of the composition.

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

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