Oxylipin in the treatment of seborrhea

Abstract

The present invention relates to oxylipins used in the treatment of seborrhea. Oxylipins are particularly present in oily plant extracts, and preferably in oily plant extracts rich in oxylipins. The present invention also relates to dermatological cosmetics or dermatological compositions used in the treatment of seborrhea, comprising at least one oxylipin, preferably an oxylipin derived from an oily plant, and at least one excipient that is acceptable for use in dermatological cosmetics or dermatological applications.

Description

Technical Field

[0001] The present invention relates to oxylipins, particularly plant extracts containing them, and to cosmetic or dermatological compositions for use in the treatment of sebum regulation, particularly seborrhea and / or acne, preferably seborrhea, containing the same.

Background Art

[0002] Living organisms are composed of one or more cells that are either prokaryotic or eukaryotic, and their functions of survival, defense, and growth depend on the metabolism of three major chemical groups: carbohydrates, proteins, and lipids.

[0003] Lipids are natural substances and their roles are fundamental. Lipids are major components of cell structures, such as phospholipids and glycolipids in membranes. Lipids are also storage substances as an energy source for organisms. Lipids are involved in cell defense or signal transduction mechanisms and constitute coating elements such as waxes or cutins (Cuvelier et al., 2004).

[0004] Lipids are hydrophobic, and in some cases amphiphilic substances, and are soluble in nonpolar or moderately polar organic solvents.

[0005] Simple lipids are esters of fatty acids and alcohols and are distinguished from complex lipids such as phospholipids or glycolipids. The alcohol can be glycerol (constituting triglycerides) or a high molecular weight aliphatic alcohol (constituting ceramides).

[0006] Fatty acids are the fundamental constituent elements of lipids. In vivo, they can have two additive origins: biosynthesis by organisms and diet. <​Fatty acids are aliphatic monocarboxylic acids of variable length. The most common natural fatty acids have 4 to 28 carbon atoms. The length of the carbon chain and the number and type of unsaturated bonds also vary. Saturated fatty acids, monounsaturated fatty acids (one double bond), and polyunsaturated fatty acids (multiple double bonds) are distinguished. Unsaturated fatty acids in living organisms can contain 1 to 6 double bonds. Even with the same chemical formula, numerous isomers can exist not only depending on the position of the double bonds, but also on whether they are in the cis or trans configuration.

[0008] In the plant kingdom, fatty acids can be oxidized in ketone form (e.g., lycanic acid), hydroxylated form (e.g., ricinoleic acid), or epoxy form (e.g., pernolic acid).

[0009] Generally, triglycerides are heterogeneous, and vegetable oils are complex mixtures of triesters.

[0010] In the plant kingdom, triacylglycerols are typically stored as oily inclusions (oleosomes derived from the endoplasmic reticulum), which can aggregate within the cells of reserve tissues to form large clusters. This is particularly pronounced in seeds, where triacylglycerols can account for more than 50% of the dry mass. Exceptionally, seeds may accumulate fatty acid esters and long-chain aliphatic alcohols instead of triglycerides (e.g., jojoba). Less commonly, some fruits have triglyceride concentrations in their pericarp (e.g., olives, avocados, bay laurel).

[0011] Omega-3 and omega-6 fatty acids, essential for humans, such as arachidonic acid (C20:4 n-6), eicosapentaenoic acid (C20:5 n-3), and docosahexaenoic acid (C22:6 n-3), cannot be synthesized by the enzymes (enzyme arsenals) of vertebrates without the essential supply of linoleic acid and alpha-linolenic acid. Therefore, these nutrients are called essential nutrients and must be supplied through food. These polyunsaturated fatty acids are mainly present in food in esterified, unesterified, or free forms, such as triacylglycerols, sterol esters, and phospholipids (Liu et al., 2015).

[0012] The main plant-based sources of linoleic acid include soybean oil, sunflower oil, safflower oil, evening primrose oil, and rice bran oil.

[0013] The main plant-based sources of alpha-linolenic acid include rapeseed oil, linseed oil, camelina oil, chia oil, canola oil, soybean oil, perilla oil, or walnut oil.

[0014] Several oily macroalgae and microalgae are also sources of polyunsaturated fatty acids (Van Ginneken et al., 2011).

[0015] Polyunsaturated fatty acids are substrates for many enzymatic and non-enzymatic reactions that produce oxygenated metabolites with various functions, known as oxylipins. Oxylipins include oxidized polyunsaturated fatty acids and their derivatives. These are found in mammals, flowering plants (angiosperms), mosses, algae, bacteria, and fungi. Oxylipins include signaling molecules, ligands for transcription factors, or precursors for lipid mediator synthesis (Calder, 2012). For example, eicosanoids, including leukotrienes and prostanoids, are a large group of oxidized derivatives of polyunsaturated fatty acids containing 20 carbon atoms. Docosasanoids are enzymatic oxidation products of polyunsaturated fatty acids with 22 carbon atoms, such as docosahexaenoic acid. Oxidation products of polyunsaturated fatty acids with 18 carbon atoms, such as linoleic acid or gamma-linolenic acid, are classified as octadecanoic acids. Octadecanoids derived from linoleic acid include 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE). These two molecules have been described as in vivo oxidation markers (Lagarde, 2011). Hydroperoxy, epoxy, or ketone forms derived from linoleic acid have also been reported (Richardson et al., 2017). The best-known oxygenated metabolite of γ-linolenic acid is that which produces jasmonic acid, a cyclic derivative with plant pathogen resistance activity, which has been described in detail (Blee, 2002).

[0016] The oxidation of polyunsaturated fatty acids can proceed both non-enzymatically and enzymatically (Oenel et al., 2017). In the latter case, the location of the unsaturated bond on the polyunsaturated fatty acid and the enzymatic environment determine the type of oxylipin formed. The main pathways are those of cyclooxygenase, lipoxygenase, and cytochrome P-450 (Andreou et al., 2009). While the enzymatic pathway is considered the primary route for producing oxygenated fatty acids from free polyunsaturated fatty acids, some studies have shown that the oxidation of polyunsaturated fatty acids, particularly their esterified forms (especially triglycerides), can proceed via non-enzymatic pathways. This can occur in oily plant matrices due to the action of free radicals, whose generation is promoted by storage conditions (temperature, duration, etc.). These oxidized fatty acids can be released after de-esterification, particularly by the action of lipases (Oenel et al., 2017).

[0017] Oxylipins are present in polyunsaturated vegetable oils or oily polyunsaturated fatty acid plant matrices of plants or algae. Algae are a source of polyunsaturated fatty acids and may contain enzymes that form oxylipins (Richardson et al., 2017). Furthermore, their synthesis can be promoted even in low-oil tissues under certain conditions, such as tobacco leaves exposed to cryptogenin (Rusterucci et al., 1999). Finally, patent application FR2789085 describes a method for obtaining an oil rich in hydroxyoctadecadiene fatty acids, particularly 9-hydroxyoctadecadiene, from an oily mixture containing linoleic acid. Hydroxyoctadecadiene fatty acids are obtained by controlled oxidation of linoleic acid, and / or α-linolenic acid, and / or γ-linolenic acid, or their esters, in the presence of an oxidation catalyst such as an iron halide or copper halide.

[0018] Sebaceous glands are exocrine glands found throughout the skin, except for the palms of the hands and soles of the feet. They are particularly abundant in the seborrheic areas of the face, especially the T-zone (the central area of ​​the face that forms a T-shape), the back, and the torso. They are usually associated with hair follicles. Therefore, the follicular sebaceous gland unit is also discussed. Sebaceous glands are responsible for the synthesis and secretion of sebum by sebaceous cells, which are the epithelial cells that make up the gland.

[0019] Sebum is a complex of lipids synthesized under hormonal stimulation. It is an essential component of the water-lipid film that protects the skin from external stimuli and dehydration, playing a major barrier role. In addition, related to this barrier function, sebum possesses antibacterial properties due to oleic acid and palmitoleic acid, and antioxidant power provided by vitamin E. Therefore, sebum contributes to maintaining the integrity of the skin barrier.

[0020] Seborrhea is characterized by excessive sebum secretion from the sebaceous glands. This causes cosmetic problems. The skin has a shiny appearance, the complexion is dull, and the sebaceous gland openings of the hair follicles are dilated. Furthermore, in this type, also known as oily skin, makeup does not hold well. In scalp seborrhea, the hair becomes oily and dull, making styling difficult. In severe cases of seborrhea, the hair is said to be oily and fluid and may be accompanied by a foul odor.

[0021] Acne is a chronic inflammatory skin disease affecting the follicular sebaceous gland units, leading to the formation of obstructive lesions, i.e., open and / or closed comedones. It is important not to underestimate this condition and to treat it properly, especially because it can lead to psychosocial distress due to scarring.

[0022] During acne development, the regulation of the sebaceous glands is disrupted, affecting the quantity and quality of sebum, primarily due to various endogenous factors such as hormones, as well as external factors such as pollution, poor diet, and stress. In fact, the skin of acne patients is characterized by increased sebum secretion, known as hyperseborrhea, and changes in the overall sebum composition, known as dysseborrhea. The lipid ratios present in the sebum of subjects with acne differ from those of healthy skin, with significantly increased levels of free fatty acids, squalene and its oxides, and waxes.

[0023] This degenerated seborrhea, i.e., more viscous sebum, along with keratinization disorders, contributes to the obstruction of hair follicle ducts. Furthermore, this creates a favorable culture medium for the development of pro-inflammatory acne bacteria, such as Cutibacterium acnes, which is currently the most well-known. Thus, all these factors can lead to the development of the initial acne lesions, open and closed comedones, which can progress to more severe inflammatory lesions (papules, pustules, and nodules).

[0024] Therefore, there is always a need to provide effective solutions to treat seborrhea and, consequently, acne, and to resolve the aesthetic problems associated with seborrhea. [Overview of the project]

[0025] Therefore, the objective of the present invention is to satisfy these needs. In fact, the inventors have surprisingly demonstrated that extracts rich in oxylipins derived from various plants have the ability to reduce sebum production. Such anti-seborrheic effects are particularly beneficial in patients with acne-prone skin.

[0026] The present invention also relates to a mixture of oxylipins, such as plant extracts containing or rich in at least one oxylipin, for use in the treatment of seborrhea and / or acne, preferably seborrhea.

[0027] Furthermore, the present invention also relates to the use of a mixture of oxylipins, such as at least one oxylipin, particularly plant extracts rich in or containing oxylipins, in the preparation of a skin cosmetic or dermatological composition for the treatment of seborrhea and / or acne, preferably seborrhea.

[0028] Furthermore, the present invention also relates to the use of a mixture of oxylipins, such as at least one oxylipin, particularly plant extracts rich in or containing oxylipins, in the treatment of seborrhea and / or acne, preferably seborrhea.

[0029] Furthermore, the present invention relates to a method for treating seborrhea and / or acne, preferably seborrhea. The method comprises administering to a person in need an effective amount of a mixture of oxylipins, such as at least one oxylipin, particularly plant extracts rich in or containing oxylipins.

[0030] Furthermore, the present invention also relates to a dermo-cosmetic or dermatological composition comprising a mixture of oxylipins, such as at least one oxylipin, particularly plant extracts rich in or containing oxylipins, used for the treatment of seborrhea and / or acne, preferably seborrhea, and at least one dermatological cosmetic or dermatologically acceptable excipient.

[0031] Furthermore, the present invention also relates to the use of a skin cosmetic or dermatological composition comprising a mixture of oxylipins, such as at least one oxylipin, particularly plant extracts rich in or containing oxylipins, and at least one skin cosmetic or dermatologically acceptable excipient, in the preparation of a pharmaceutical product for the treatment of seborrhea and / or acne, preferably seborrhea.

[0032] The present invention also relates to a method for treating seborrhea and / or acne, preferably seborrhea. The method involves administering to a person in need an effective amount of a mixture of oxylipins, such as a plant extract containing or rich in oxylipins, together with a skin cosmetic or dermatological composition comprising at least one skin cosmetic or dermatologically acceptable excipient.

[0033] In the context of the present invention, a preferred form of oxylipin may be a mixture of oxylipins. Oxylipins are derived particularly from plants, especially oily plant materials, and may be present in plant extracts, especially plant extracts rich in oxylipins. The plant extract is particularly an oily plant extract, and is preferably rich in oxylipins.

[0034] definition In this invention, "approximately" means that the value may be 10%, particularly 5%, more specifically 2%, and even more specifically 1% lower or higher than the indicated value.

[0035] In this invention, "extract" or "plant extract" means a substance obtained after extracting a plant or a part of a plant (for example, a plant-derived vegetable oil) using a solvent called an extraction solvent. This may be obtained in a concentrated or dried form by partially or completely evaporating the extraction solvent. In particular, it may be a dried extract. Extraction can also be carried out by mechanical processes such as pressurization.

[0036] In this invention, "dried extract" means an extract that does not contain an extraction solvent, or contains an extraction solvent only in trace amounts. Therefore, such a dried extract contains only substances derived from plant materials. It may also contain trace amounts of an extraction solvent.

[0037] In the present invention, "oleaginous plant material" means an oily plant or a part of a plant, i.e., a plant rich in fat. Examples include oily seeds or fruits (e.g., apple seeds, soybeans, flax seeds, safflower seeds, cumin seeds, camelina seeds, canola seeds, shiso seeds, chia seeds, rapeseed seeds, hazelnuts, or mixtures thereof), gametophytes (e.g., brown algae, especially Saccharina latissima), or mixtures thereof. It may also include vegetable oils (e.g., apple seed oil, soybean oil, linseed oil, safflower oil, cumin oil, rice bran oil, camelina oil, canola oil, shiso oil, chia oil, rapeseed oil, hazelnut oil, or mixtures thereof).

[0038] In the present invention, "oil-based plant extract" means an extract obtained from an oil-based plant material as defined above.

[0039] In the present invention, "fatty acid" means a carboxylic acid R1CO2H. Here, chain R1 is a linear or branched hydrocarbon chain, which is saturated or contains one or more, particularly one, two, three, four, five, or six C=C double bonds. The carboxylic acid contains 10 to 28, preferably 14 to 24, and particularly 16 to 22 carbon atoms (including the carbon atoms of the carboxylic acid functional group).

[0040] In the present invention, "polyunsaturated fatty acid" means a fatty acid as defined above, in which the hydrocarbon chain contains one or more, particularly one, two, three, four, five, or six C=C double bonds.

[0041] In the present invention, "free fatty acid" means a fatty acid that is not bound to other molecules (for example, those that combine with glycerol or its derivatives to form glycerides, or those that combine with alcohols to form fatty esters).

[0042] In the present invention, "oxylipin" means an oxygenated molecule derived from the enzymatic or non-enzymatic oxidation of a polyunsaturated fatty acid. Oxidation of a polyunsaturated fatty acid makes it possible to introduce one or more, particularly one, two, or three oxygenating groups. These oxygenating groups are selected from hydroxyl groups (-OH), hydroperoxy groups (-OOH), keto groups (=O; oxygen is double-bonded to a carbon atom), and epoxy groups (-O-; oxygen is bonded to two adjacent carbon atoms), and preferably, it is possible to introduce one, two, or three hydroxyl groups and / or keto groups. In particular, it is possible to form conjugation with another double bond by substituting one or more (particularly one, two, or three) C=C double bonds, and / or substitution of C=C units for C(GO1)-C(GO2) units. Here, GO1 and GO2 each independently represent the oxygenating groups defined above. Oxylipins can be octadecanoids, eicosanoids, or mixtures thereof.

[0043] In the present invention, "octadecanoid" means an oxygenated molecule derived from the enzymatic or non-enzymatic oxidation of a polyunsaturated fatty acid containing 18 carbon atoms, as defined above. The polyunsaturated fatty acid containing 18 carbon atoms can be, for example, linoleic acid, α-linolenic acid, γ-linolenic acid, or stearidonic acid, preferably linoleic acid, α-linolenic acid, or γ-linolenic acid. Examples include 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE), 9-hydroperoxy-10E,12Z-octadecadienoic acid (9-HpODE), 13-hydroperoxy-9Z,11E-octadecadienoic acid (13-HpODE), and 9,10-dihydroxy -12Z-octadecadienoic acid (9,10-DiHOME), 12,13-dihydroxy-9Z-octadecadienoic acid (12,13-DiHOME), 9,12,13-trihydroxy-10E-octadecadienoic acid (10-TriHOME), 9-keto-10E,12Z-octadecadienoic acid (9-OxoODE), 13-keto-9Z,11E-octadecadienoic acid 13-OxoODE, 9-hydroxy-10E,12Z,15Z-octadecatrienoic acid (9-HOTrE), 13-hydroxy-9Z,11E,15Z-octadecatrienoic acid (13-HOTrE), 9-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid (9-HpOTrE), 11-hydroperoxy-9Z,12Z,15Z-O Examples include tadecatrienoic acid (11-HpOTrE), 12-hydroperoxy-9Z,13E,15E-octadecatrienoic acid (12-HpOTrE), 13-hydroperoxy-9Z,11E,15Z-octadecatrienoic acid (13-HpOTrE), 12,13-epoxy-9Z-octadecenoic acid (12,13-EpOME), or mixtures thereof.

[0044] In the present invention, "eicosanoid" means an oxygen compound derived from the enzymatic or non-enzymatic oxidation of a polyunsaturated fatty acid containing 20 carbon atoms as defined above, and this polyunsaturated fatty acid containing 20 carbon atoms may be, for example, arachidonic acid or eicosapentaenoic acid. Examples include leukotrienes and / or prostanoids. Examples include 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid (5-HEPE), 12-hydroxy-5Z,8Z,10E,14Z,17Z-eicosapentaenoic acid (12-HEPE), 15-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid (15-HEPE), 15-hydroperoxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid (15-HpEPE), 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE), 8-hydroxy-5Z,9E,11Z,14Z-eicosatetraenoic acid (8-HETE), and 9-hydroxy-5Z,7E,11Z,14Z-eicosapentaenoic acid. Examples include cosatetraenoic acid (9-HETE), 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE), 15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-HETE), 5-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HpETE), 11-hydroperoxy-5Z,8Z,12E,14Z-eicosatetraenoic acid (11-HpETE), 12-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HpETE), 15-hydroperoxy-5Z,8Z,11Z,13E-arachidonic acid (15-HpETE), or mixtures thereof.

[0045] In the present invention, "oxylipin-rich extract" means an extract as defined above obtained from a plant or a part thereof containing oxylipins, in which the synthesis of oxylipins is promoted, or an extract as defined above obtained after undergoing an oxylipin concentration step (e.g., by chromatography).

[0046] In the present invention, "non-polar solvent" means a lipophilic solvent capable of solubilizing low-polarity compounds, i.e., compounds with a LogP of 1 or higher, and is selected from, for example, heptane, hexane, limonene, chloroform, dichloromethane, supercritical CO2, supercritical CO2 / ethanol mixtures, and mixtures of these solvents. Examples also include 100% bio-derived lipophilic solvents such as EcoXtract® LIPOCOS (supplier: Pennakem Europa).

[0047] In the present invention, "hydrophilic solvent" means a polar solvent selected from, for example, water, subcritical water, water-miscible alcohols (e.g., C1-C3 alcohols, C3-C5 glycols, glycerol, acetone, etc.), and mixtures thereof.

[0048] In the present invention, "organic solvent that is immiscible with vegetable oil" means an organic solvent that is either immiscible or only partially immiscible with vegetable oil, thereby forming a heterogeneous mixture of the organic solvent and vegetable oil in which at least two different phases can be observed.

[0049] In the present invention, "C1-C3 alcohol" refers to an alcohol R2OH in which the R2 chain is a saturated linear or branched hydrocarbon chain containing 1 to 3 carbon atoms. Examples include methanol, ethanol, n-propanol, or isopropanol, with methanol, ethanol, or isopropanol being particularly preferred. Ethanol is preferred.

[0050] In the present invention, "C3-C5 glycol" means a saturated linear or branched hydrocarbon chain consisting of 3 to 5 carbon atoms, wherein the chain has two OH functional groups. For example, propylene glycol is an example.

[0051] In the present invention, "ambient temperature" means a temperature that includes the range of 15 to 40°C, preferably 20 to 30°C, and particularly about 25°C. [Modes for carrying out the invention]

[0052] This invention relates to oxylipins, including mixtures of oxylipins. Oxylipins can take the form of plant extracts containing or rich in oxylipins and are used for the treatment of seborrhea and / or acne, preferably seborrhea. Seborrhea can be seborrhea of ​​the skin or scalp.

[0053] The definition of oxylipin is as stated above, and may be selected in particular from octadecanoids, eicosanoids and mixtures thereof. Thus, oxylipin is 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE), 9-hydroperoxy-10E,12Z-octadecadienoic acid (9-HpODE), 13-hydroperoxy-9Z,11E-octadecadienoic acid (13-HpODE), 9,10-dihydroxy-12Z-octadecadienoic acid (9,10-DiHOME), 12,13-dihydroxy-9Z-octadecadienoic acid (12,13-Di HOME), 9,12,13-trihydroxy-10E-octadecadienoic acid (10-TriHOME), 9-keto-10E,12Z-octadecadienoic acid (9-OxoODE), 13-keto-9Z,11E-octadecadienoic acid (13-OxoODE), 9-hydroxy-10E,12Z,15Z-octadecatrienoic acid (9-HOTrE), 13-hydroxy-9Z,11E,15Z-octadecatrienoic acid (13-HOTrE), 9-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid (9-H pOTrE), 11-hydroperoxy-9Z,12Z,15Z-octadecatrienoic acid (11-HpOTrE), 12-hydroperoxy-9Z,13E,15E-octadecatrienoic acid (12-HpOTrE), 13-hydroperoxy-9Z,11E,15Z-octadecatrienoic acid (13-HpOTrE), 12,13-epoxy-9Z-octadecenoic acid (12,13-EpOME), 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid (5-HEPE), 12-hydroxy-5Z ,8Z,10E,14Z,17Z-eicosapentaenoic acid (12-HEPE), 15-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid (15-HEPE), 15-hydroperoxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid (15-HpEPE), 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE), 8-hydroxy-5Z,9E,11Z,14Z-eicosatetraenoic acid (8-HETE), 9-hydroxy-5Z,7E,11Z,Examples include 14Z-eicosatetraenoic acid (9-HETE), 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE), 15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-HETE), 5-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HpETE), 11-hydroperoxy-5Z,8Z,12E,14Z-eicosatetraenoic acid (11-HpETE), 12-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HpETE), 15-hydroperoxy-5Z,8Z,11Z,13E-arachidonic acid (15-HpETE), and mixtures thereof.

[0054] According to a particular embodiment, the oxylipin is selected from 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE, 12,13-DiHOME, 15-HEPE, and mixtures thereof.

[0055] Oxylipins are preferably present in plant extracts, preferably in plant extracts rich in oxylipins. The plant extract contains at least one oxylipin as defined above, particularly selected from 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE, 12,13-diHOME, 15-HEPE, and mixtures thereof. More specifically, the plant extract may be an oily plant extract, preferably an oily plant extract rich in oxylipins. This can be obtained from a variety of oily plant materials.

[0056] Oily plant material refers to an oily plant or a part thereof that is rich in vegetable oil containing fats, particularly polyunsaturated fatty acids. Therefore, oily plant material may be, for example, a vegetable oil containing polyunsaturated fatty acids. Oily plant material may also be a gametophyte, and preferably a gametophyte containing polyunsaturated fatty acids.

[0057] Vegetable oils containing polyunsaturated fatty acids more specifically include polyunsaturated fatty acids containing 18 carbon atoms (C18), such as linoleic acid, alpha-linolenic acid, or gamma-linolenic acid; polyunsaturated fatty acids containing 20 carbon atoms (C20), such as arachidonic acid or eicosapentaenoic acid; or mixtures thereof. Preferably, the polyunsaturated fatty acid content in the vegetable oil is at least 10% by weight, preferably at least 40% by weight, relative to the total fatty acid weight in the vegetable oil. Preferably, the C18 and / or C20 polyunsaturated fatty acid content in the vegetable oil is at least 15% by weight, preferably at least 40% by weight, relative to the total fatty acid weight in the vegetable oil.

[0058] Vegetable oils containing polyunsaturated fatty acids include, for example, apple seed oil, soybean oil, linseed oil, safflower oil, cumin oil, rice bran oil, camelina oil, canola oil, perilla oil, chia oil, rapeseed oil, hazelnut oil, or mixtures thereof. The gametophyte may be the gametophyte of brown algae such as Saccharina latissima.

[0059] Oily plant extracts, preferably those rich in oxylipins, include apple seed extracts (especially apple seed oil), soybean extracts (especially soybean oil), hazelnut extracts (especially hazelnut oil), or extracts of the gametophytes of brown algae such as Saccharina latissima, and these extracts contain oxylipins and are preferably rich in oxylipins.

[0060] Preferably, the oily plant extract is not a hazelnut extract such as hazelnut oil.

[0061] According to certain embodiments of the present invention, the synthesis of oxylipins in a plant or a part thereof (e.g., vegetable oil or gametophyte) can be promoted before extraction of the plant or a part thereof. This means modifying the growth or cultivation parameters of the plant or a part thereof to promote the synthesis of oxylipins in the plant or a part thereof, thereby increasing the oxylipin content in the plant or a part thereof.

[0062] In plants or parts thereof, oxylipin synthesis can be promoted by optimizing parameters such as temperature, which promotes oxidation processes, or by applying enzymatic treatment.

[0063] Furthermore, oxylipin synthesis can also be promoted by induction (elicitation), particularly in plant cell cultures (e.g., gametophytes).

[0064] According to another embodiment, plant extracts can be concentrated for oxylipins, for example, by molecular distillation and / or fractionation of the extract, particularly by chromatographic techniques. Prior to extraction from the plant or a part thereof, the synthesis of oxylipins in the plant or a part thereof can be promoted as described above.

[0065] When a plant or a part thereof is a vegetable oil containing polyunsaturated fatty acids (hereinafter referred to as "vegetable oil"), the vegetable oil can be obtained by cold pressing at room temperature without heating, preferably through a subsequent filtration step, by pressing oily plant raw materials (e.g., grains, seeds, etc.).

[0066] Vegetable oil can also be obtained by extracting oily plant raw materials (grains, seeds, etc.) whole or in a pulverized state using a nonpolar solvent. Such extraction can be carried out using supercritical CO2 with or without the addition of ethanol as a cosolvent, and a subsequent filtration step can be performed as desired.

[0067] Vegetable oil can also be obtained by extraction from oily plant raw materials using a hydrophilic solvent in the presence of at least one enzyme (e.g., pectinase), particularly in the presence of an enzyme mixture such as pectinase.

[0068] Preferably, the vegetable oil is obtained by pressing oily plant raw materials, particularly by cold pressing at room temperature without heating, and preferably by a subsequent filtration step.

[0069] Oily plant extracts can be obtained by extracting vegetable oils using an aqueous hydrotropic solution, subcritical water, or an organic solvent that is immiscible with vegetable oil (optionally mixed with water). The concentration of oxylipins in oily plant extracts can be increased, for example, by molecular distillation of the extract or by fractionation of the extract using techniques.

[0070] Organic solvents that are immiscible with vegetable oil may be used as a mixture with water, and in particular, a volume ratio of organic solvent / water in the range of 80 / 20 to 100 / 0, especially in the range of 85 / 15 to 95 / 5, and especially about 90 / 10.

[0071] The organic solvent that is immiscible with the vegetable oil may be a C1-C3 alcohol, which may be optionally mixed with water, particularly in the volume ratio of the organic solvent to water described above. More specifically, the C1-C3 alcohol is methanol, ethanol, n-propanol, or isopropanol, and is particularly methanol, ethanol, or isopropanol, preferably ethanol.

[0072] The extraction solvent may be selected from methanol, methanol / water mixtures, ethanol, ethanol / water mixtures, isopropanol, and isopropanol / water mixtures. According to a preferred embodiment, the extraction solvent is methanol, an ethanol / water mixture in a volume ratio of about 90 / 10, or an isopropanol / water mixture in a volume ratio of about 90 / 10.

[0073] According to a preferred embodiment, an oily plant extract can be obtained by the method of the present invention described below.

[0074] A method for preparing an oily plant extract includes the step of extracting a plant oil using an extraction solvent comprising an aqueous hydrotropic solution, subcritical water, or an organic solvent that is incompatible with plant oil, particularly an extraction solvent consisting of an aqueous hydrotropic solution, subcritical water, or an organic solvent that is incompatible with plant oil, and optionally mixing it with water.

[0075] According to a particular embodiment, the extraction solvent comprises an organic solvent that is immiscible with vegetable oil, and in particular consists of an organic solvent that is immiscible with vegetable oil, and is optionally mixed with water.

[0076] Organic solvents that are incompatible with vegetable oil may be C1-C3 alcohols in particular.

[0077] The extraction solvent may be, in particular, a C1-C3 alcohol mixed with water as an option.

[0078] The C1-C3 alcohols are methanol, ethanol, n-propanol, or isopropanol, and are particularly methanol, ethanol, or isopropanol. Ethanol is preferred.

[0079] Organic solvents that do not mix with vegetable oils, especially C1-C3 alcohols such as methanol, ethanol, or isopropanol, may be used as mixtures with water, particularly in volume ratios where the organic solvent / water ratio is in the range of 80 / 20-100 / 0, especially 85 / 15-95 / 5, and especially about 90 / 10.

[0080] The extraction solvent can be selected from methanol, methanol / water mixture, ethanol, ethanol / water mixture, isopropanol, and isopropanol / water mixture.

[0081] According to a preferred embodiment, the extraction solvent is methanol, an ethanol / water mixture in a volume ratio of about 90 / 10, or an isopropanol / water mixture in a volume ratio of about 90 / 10.

[0082] The vegetable oil extraction step involves mixing the vegetable oil with the extraction solvent for 1 to 12 hours, and is carried out at a temperature range of 15 to 25°C, particularly around 20°C. The amount of extraction solvent used to carry out this extraction is preferably 0.5 to 3 g, particularly 1 to 3 g, per 1 g of vegetable oil.

[0083] At the end of the extraction, the extract phase and the lipid phase are obtained. The extract phase is advantageously separated from the lipid phase and partially or completely recovered, especially under vacuum, before drying. This removes more or less of the extraction solvent, yielding a dry extract if the solvent is completely removed, or a concentrated extract if diluted with the residual solvent.

[0084] According to one embodiment of the present invention, the method of the present invention includes the following two consecutive steps: 1. Obtaining vegetable oil, and 2. Extracting vegetable oil using an extraction solvent comprising an aqueous hydrotropic solution, subcritical water, or an organic solvent that is immiscible with vegetable oil and optionally mixed with water, particularly an extraction solvent consisting of an aqueous hydrotropic solution, subcritical water, or an organic solvent that is immiscible with vegetable oil and optionally mixed with water.

[0085] According to a preferred embodiment of the present invention, the method of the present invention includes the following sequence of steps: 1. To obtain vegetable oil at will, 2. Extracting vegetable oil with an extraction solvent comprising an aqueous hydrotropic solution, subcritical water, or an organic solvent that is immiscible with plant achenes oil mixed with water, in particular an extraction solvent comprising an aqueous hydrotropic solution, subcritical water, or an organic solvent that is immiscible with plant achenes oil mixed with water, to obtain an extract phase and a lipid phase. 3. Collect the extracted phase obtained in step (2), and 4. Partially or completely dry the extracted phase to produce a concentrated extract or dried extract of the present invention.

[0086] Step (1) can be carried out by pressing an oily plant material (e.g., grains, seeds, etc.), and is particularly possible by cold pressing at room temperature without heating, i.e., non-heating pressing, followed by a filtration step.

[0087] Step (2) is preferably carried out using the extraction solvent defined above.

[0088] The extraction solvent may be methanol, ethanol, or isopropanol, and may be optionally mixed with water, particularly in a volume ratio of 80 / 20 to 100 / 0, especially in the range of 85 / 15 to 95 / 5, and especially about 90 / 10. A preferred extraction solvent is an ethanol / water mixture with a volume ratio of about 90 / 10.

[0089] The extraction step (2) can be carried out by mixing the vegetable oil with the extraction solvent for 1 to 12 hours, and can be carried out particularly at a temperature of 15 to 25°C, especially about 20°C. The amount of extraction solvent used for this extraction is preferably 0.5 to 3 g, particularly 1 to 3 g, per 1 g of vegetable oil. This extraction step (2) ultimately yields the desired extraction phase and lipid phase.

[0090] Step (3) is preferably carried out by separating the extracted phase from the lipid phase.

[0091] Step (4) is preferably carried out under vacuum.

[0092] An extract rich in oxylipins contains, in particular, at least 25% by weight, for example, at least 30% by weight, for example, at least 40% by weight, for example, at least 50% by weight, for example, at least 60% by weight, for example, at least 70% by weight, for example, at least 80% by weight, for example, at least 90% by weight of oxylipins, based on the weight of the dry extract. An extract rich in oxylipins may contain up to 100% by weight of oxylipins.

[0093] The present invention also relates to a dermatological cosmetic or dermatological composition for the treatment of seborrhea and / or acne, preferably seborrhea, comprising at least one oxylipin as described above and at least one additive that is acceptable as a dermatological cosmetic or dermatologically approved. Seborrhea can be seborrhea of ​​the skin or scalp.

[0094] More specifically, oxylipins are plant-derived, and more specifically, oily plant materials, and may be present in the plant extracts defined above, more specifically, plant extracts rich in oxylipins. The plant extracts are more specifically oily plant extracts defined above, and preferably oily plant extracts rich in oxylipins. The oily plant extracts are more specifically apple seed extracts (more specifically apple seed oil), soybean extracts (more specifically soybean oil), hazelnut extracts (more specifically hazelnut oil), or extracts from the gametophytes of brown algae such as Saccharina latissima, and such extracts therefore contain oxylipins.

[0095] The dermatological cosmetics or compositions of the present invention are typically in forms suitable for topical use. Therefore, the dermatological cosmetics or compositions of the present invention are not intended to be washed off after application (typically, the skin should not be washed or cleansed for at least 12 hours after application of the composition). Accordingly, the dermatological cosmetics or compositions may be provided in forms commonly known for topical administration, i.e., in particular, in the form of lotions, milks, emulsions, serums, balms, masks, creams, dispersions, gels, foams, sprays, and shampoos.

[0096] Furthermore, dermatological cosmetics or dermatological compositions may also contain surfactants, chelating agents, preservatives, antioxidants such as tocopherol, stabilizers, emulsifiers, thickeners, gelling agents, humectants, emollients, trace elements, essential oils, fragrances, dyes, matting agents, chemical or mineral sunscreens, moisturizing agents, and hot spring water.

[0097] The following examples and drawings are intended to illustrate the scope of the invention, but are not intended to limit it. [Brief explanation of the drawing]

[0098] [Figure 1]This is a high-performance liquid chromatography (HPLC) chromatogram (UV 236 nm) of a lipid extract of the gametophyte of Saccharina latissima, showing the presence of molecules exhibiting characteristic UV spectra of oxylipins, particularly 12(S)-HEPE and 15(S)-HEPE. It is most rich in oxylipin 15(S)-HEPE. [Figure 2] Production of oxylipins from Saccharina latissima gametophytes suspended in culture medium for 48 hours. The culture medium was either without phosphate (control) or with phosphate (75 mg / L K2HPO4 + 50 mg / L β-glycerophosphate Na2 × H2O) and / or with iron Fe3+ (0.91 mg / L FeCl3·6H2O). Oxylipin content is expressed as the equivalent amount of 15(S)-HEPE (mg) per liter of suspension. [Figure 3] Changes over time in the amount of oxylipin produced per liter of culture medium (equivalent to 15(S)HEPE (mg)) in culture medium A (control) and B (phosphate-rich culture medium). [Figure 4] Changes over time in the amount of oxylipins (equivalent to 15(S)HEPE (mg)) per liter of culture medium A (control) and B (induced by phosphate and iron). Induction (indicated by arrows) was performed on day 34 of culture by adding phosphate (75 mg / L K2HPO4 + 50 mg / L β-glycerophosphate Na2 × H2O) and iron Fe3+ (1 mg / L FeCl3·6H2O) to the culture medium. [Examples]

[0099] Example 1: Lipid extract obtained from apple seed oil The lipid extract was obtained as follows: Apple seed oil is prepared by cold-pressing apple seeds (Pyrus malus L.) to obtain an apple seed oil in which the linoleic acid content in the fatty acid fraction is 50% by weight; Apple seed oil is extracted using an ethanol / water mixture (90 / 10 v / v), with 2 grams of the ethanol / water mixture per gram of oil, at 20°C for 2 hours; The ethanol phase was recovered, and the solvent was evaporated under vacuum to prepare the lipid extract.

[0100] Lipid extracts were obtained with an extraction mass yield of approximately 1%. The main octadecanoids were 10-ToriHOME, 13-HODE, 9-HODE, 13-OxoODE, and 9-OxoODE.

[0101] Example 2: Lipid extract obtained from soybean oil The lipid extract was obtained as follows: Soybean oil is prepared by cold-pressing soybeans (Glycine max (L.) Merr.) to obtain a fatty acid fraction consisting of 55% linoleic acid and 8% alpha-linolenic acid. Soybean oil was extracted using an ethanol / water mixture (90 / 10 v / v), with 2 grams of the ethanol / water mixture per gram of oil, at 20°C for 2 hours. The ethanol phase was recovered, and the solvent was evaporated under vacuum to prepare the lipid extract.

[0102] Lipid extracts were obtained with an extraction mass yield of approximately 5.5%. The main octadecanoids were 10-ToriHOME, 13-HODE, 9-HODE, 13-OxoODE, and 9-OxoODE.

[0103] Example 3: Lipid extract obtained from hazelnut oil Lipid extracts were obtained as follows: • Hazelnut oil is prepared by cold-pressing shelled hazelnuts (Corylus avellana L.) to produce a fatty acid fraction with a linoleic acid content of 15%. • Extract hazelnut oil using an ethanol / water mixture (90 / 10 v / v), using 2 grams of ethanol / water mixture per gram of oil, at 20°C for 2 hours; The ethanol phase is recovered, and the solvent is evaporated under vacuum to obtain the lipid extract.

[0104] Lipid extracts were obtained with an extraction mass yield of approximately 1.5%. The main octadecanoids were 10-TriHOME, 13-HODE, 9-HODE, and 12,13-DiHOME.

[0105] Example 4: Lipid extract obtained from Saccharina latissima 4a: Experiments in culture medium with and without the addition of phosphate and / or ferric iron. Male gametophyte strains of Saccharina latissima are cultured in reconstituted seawater. Biomass culture is carried out in an 18°C ​​bioreactor while supplying CO2-rich air to aerate the suspension while maintaining a pH of 8.0. Culture is carried out under a 16 / 8 hour photoperiod using a light-emitting diode. Once the biomass reaches critical density, the gametophyte biomass is collected using a nylon sieve and freeze-dried under vacuum immediately before solid / liquid extraction. This is carried out by grinding in the presence of a solvent (e.g., a 52:48 (volume ratio) ethanol / methyl ethyl ketone mixture). Grinding is carried out using a vibrating grinder (Retsch MM 400) or an ultrasonic grinder (Branson, Digital Sonifier 450). Between each grinding step, the tube containing the biomass is centrifuged at 8000 g for 10 minutes. The clarified supernatant is collected, and then the grinding step is repeated by injecting fresh solvent into the grinding tube containing the biomass pellet. The recovered supernatant fraction is decolorized. For this purpose, the fraction is diluted with purified water and incubated in the dark at 4°C. Then, the tube is centrifuged and the decolorized supernatant is collected. Next, a solvent carrier (DMSO, pentylene glycol, Eutanol® G, etc.) is added to the decolorized fraction. This ensures that the final dry material content is maintained after the solvent and water have completely evaporated, leaving only the dry material dissolved in the selected carrier.

[0106] The analysis will be performed by HPLC (using an Alliance WATERS 2695 system controlled by Empower Ver 2.03 software equipped with a WATERS 2996 diode array detector). The column used will be a CORTECS C8 2.7μ 4.6×150mm column equipped with a CORTECS C8 2.7μ 3.9×5mm VG guard column inserted in a furnace at 35°C. The mobile phase will be A=0.1% formic acid-added distilled water, B=0.1% formic acid-added acetonitrile, and C=0.1% formic acid-added methanol. The flow rate was 0.7 mL / min, and the following gradient was used: 50% A, 50% B at 1.5 min; 30% A, 70% B at 22 min; 30% A, 70% B at 25 min; 100% C at 25.1 min; 100% C at 29 min; 50% A, 50% B at 29.1 min; and 50% A, 50% B at 35 min. UV detection was performed at 236.5 nm. The device was calibrated by sequentially injecting 10 mg / L of 15(S)-HEPE (Cayman Chemical) solution, and a linear correlation was obtained between the detected area and the analyzed volume.

[0107] The chromatogram shows the presence of multiple isomers and derived oxylipins that have the same characteristic UV signature as 15(S)-HEPE (Figure 1). These form peaks in the retention time range of 10 to 30 minutes, with 15(S)-HEPE, the most abundant oxylipin, showing a retention time of 13 minutes. The oxylipin content is expressed as the 15(S)-HEPE equivalent (μg), calculated by summing the areas of the 15(S)-HEPE peak, its isomers, and the derived oxylipins.

[0108] Phosphate (75 mg / L K2HPO4 + 50 mg / L β-glycerophosphate Na2 × H2O) and / or iron Fe 3+ Sample analysis from control and derived biomass after adding (0.91 mg / L FeCl3·6H2O) to the culture medium showed that the total production of oxylipins per liter of suspension from the control culture was 0.23 mg / L, compared to phosphate or trivalent iron (Fe 3+In cultures induced using ), a similar total production of oxylipins was observed to be approximately 0.46 mg / L. Simultaneous addition of phosphate and ferric ions resulted in a total production of oxylipins reaching 0.58 mg / L per liter of suspension (Figure 2).

[0109] 4b: Culture induction experiment in a bioreactor to which phosphate was added at the start of culture. Male gametophytes of Saccharina latissima are cultured in a 10L bioreactor for 63 days. 5L of this culture is transferred to another bioreactor to prepare two parallel cultures, A and B. Both cultures A and B are supplied with 5L of pre-sterilized and chilled fresh medium. Further phosphate addition is performed only in culture B. Therefore, the phosphate concentrations in culture A are 37.5 mg / L of K2HPO4 from the culture medium and 25 mg / L of β-glycerophosphate sodium 2×H2O. In contrast, in culture B, the concentrations are 112.5 mg / L of K2HPO4 and 75 mg / L of β-glycerophosphate sodium 2×H2O, both from the culture medium and with further additions. The two cultures are carried out similarly under identical lighting, temperature, and pH control conditions. Biomass is periodically collected and frozen at -20°C. HPLC analysis of total oxylipins, expressed as 15(S)-HEPE equivalent (mg) per liter of culture medium, showed that from day 10 onwards, culture (B), which received the most phosphate, had a higher phosphate content than the control culture (A). This difference was greatest on day 15 of culture (Figure 3).

[0110] 4c: Induction experiment of bioreactor culture by adding phosphate and iron during culture Male gametophytes of Saccharina latissima were cultured in a 10L bioreactor for 63 days. 5L of this culture medium was transferred to another bioreactor to prepare two parallel culture lines, A and B. 5L of pre-sterilized and chilled fresh medium was added to both cultures A and B. The two cultures were then carried out similarly for 34 days under identical lighting, temperature, and pH control conditions. On day 34, phosphate and trivalent iron were added to culture B (induction culture) only by adding K2HPO4 75mg / L, β-glycerophosphate sodium 2×H2O 50mg / L, and FeCl3.6H2O 1mg / L. Biomass was periodically collected and stored frozen at -20°C. HPLC analysis of total oxylipins, expressed as the equivalent amount of 15(S)-HEPE (mg) per liter of culture medium, showed that from day 36 (i.e., 48 hours after the start of induction), the content of oxylipins in the induced culture (B) exceeded that of the control culture (A). This difference was observed until the end of the experiment (Figure 4).

[0111] Example 5: Effects of different plant extracts containing oxylipins on arachidonic acid-induced lipid biosynthesis in sebaceous cells Sebaceous cells are the major cell type of the sebaceous gland. These are differentiated epithelial cells that gradually accumulate lipids and release their contents through cell degradation and membrane disruption. This process is known as holocrine secretion. During differentiation, sebaceous cells accumulate large amounts of lipids in the form of lipid droplets within cytoplasmic vesicles. Sebaceous cell differentiation is regulated by multiple signaling pathways, including the PPAR-γ-dependent pathway and the COX pathway.

[0112] method: This study uses a sebaceous cell model differentiated from induced pluripotent stem cells derived from two different donors. These cells are treated with arachidonic acid to specifically induce lipid biosynthesis. This allows us to evaluate the regulatory activity of various plant extracts on lipid biosynthesis in sebaceous cells.

[0113] A lipid extract derived from apple seed oil is prepared according to Example 1.

[0114] A lipid extract derived from soybean oil is prepared according to Example 2.

[0115] A lipid extract derived from hazelnut oil is prepared according to Example 3.

[0116] Lipid extracts derived from the gametophyte of Saccharina latissima are prepared according to Example 4a.

[0117] All of these extracts are dissolved in DMSO (dimethyl sulfoxide) and tested at two different concentrations.

[0118] Sebaceous cells differentiated from induced pluripotent stem cells derived from two different donors were cultured for 3 days with a specific molecule (PhenoCULT® NPC PHENOCELL, Grasse, France) to promote maturation before the experiment. Lipid biosynthesis in sebaceous cells was induced for 48 hours with the addition of arachidonic acid (10 μM), regardless of the presence or absence of the lipid extract being tested.

[0119] The results are obtained from three independent experiments, but repeated experiments are performed to obtain n>4.

[0120] Lipid synthesis is quantified by high-resolution imaging after Bodipy staining and normalized by Hoechst staining (nuclear labeling).

[0121] Group comparisons are performed using Tukey's test following one-way ANOVA.

[0122] result: The addition of arachidonic acid (AA) resulted in a significant accumulation of total lipids in human sebaceous cells after 48 hours. These results are summarized in Table 1 below.

[0123] [Table 1]

[0124] Cannabidiol compounds are reference substances in the inhibition of lipid biosynthesis and act by activating the TRPV4 ion channel (Olah et al., 2014). When tested at a concentration of 1 μM (dissolved in DMSO), lipid accumulation was significantly suppressed. This result was as expected and supports the validity of the test (Table 1).

[0125] Lipid extract of apple seed oil The results obtained from the lipid extract of apple seed oil are shown in Table 2.

[0126] [Table 2]

[0127] Lipid extracts from apple seed oil, rich in oxylipins, significantly reduced total lipid content at the two concentrations tested (p<0.001 compared to the arachidonic acid group) (Table 2). In fact, the doubling rate of change allowed for evaluation of variability between different groups, with negative values ​​indicating suppression and values ​​less than -2 indicating a reduction of more than 50%.

[0128] The inventors have clearly demonstrated that lipid extracts from apple seed oil, rich in oxylipins, particularly the major octadecanoids (10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE), significantly and remarkably inhibit arachidonic acid-induced lipid biosynthesis in human sebaceous cells at two tested concentrations.

[0129] Lipid extract of soybean oil The results obtained from lipid extracts of soybean oil are shown in Table 3.

[0130] [Table 3]

[0131] Lipid extracts from soybean oil rich in oxylipins significantly reduced total lipids at the two concentrations tested (p<0.01 at both concentrations). In fact, the ratio change demonstrates that the reduction in total lipids significantly exceeds 50%.

[0132] The inventors have clearly demonstrated that lipid extracts from soybean oil rich in oxylipins, particularly the major octadecanoids (10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE), significantly and remarkably suppress arachidonic acid-mediated lipid biosynthesis in human sebaceous cells at two tested concentrations.

[0133] Lipid extract of hazelnut oil The results obtained from the lipid extract of hazelnut oil are shown in Table 4.

[0134] [Table 4]

[0135] Lipid extracts from hazelnut oil, which are rich in oxylipins, significantly reduced total lipids at the two concentrations tested (p<0.001 compared to the arachidonic acid group) (Table 4). In fact, at the lowest concentration tested, the ratio change reached -3.8, indicating a more than threefold reduction in total lipids.

[0136] The inventors have clearly demonstrated that hazelnut oil extracts rich in oxylipins, particularly the major octadecanoids (10-TriHOME, 13-HODE, 9-HODE, 12,13-DiHOME), significantly and remarkably inhibit arachidonic acid-mediated lipid biosynthesis in human sebaceous cells at two tested concentrations.

[0137] Saccharina latissima extract The results obtained from the Saccharina latissima extract are shown in Table 5.

[0138] [Table 5]

[0139] Saccharina latissima extract, rich in oxylipins, significantly reduced total lipids at the two concentrations tested (p<0.001 compared to the arachidonic acid group) (Table 5). In fact, the change in concentration demonstrated that 3 μg / mL of Saccharina latissima extract reduced total lipids by more than three times, and 10 μg / mL of Saccharina latissima extract reduced them by more than twelve times.

[0140] The inventors have clearly demonstrated that an extract of Saccharina latissima, rich in oxylipins, particularly eicosanoids such as 15(S)-HEPE, significantly and remarkably inhibits arachidonic acid-mediated lipid biosynthesis in human sebaceous cells at two tested concentrations.

[0141] Therefore, all these results indicate that all of these plant extracts rich in oxylipins have the ability to suppress lipid accumulation in sebaceous cells and significantly reduce sebum production.

[0142] It is interesting that remarkably different plant extracts can exhibit anti-seborrheic activity.

[0143] Example 6: Fractionation of soybean oil extract obtained according to Example 2 Protocol 1: Fractionation Conditions • Separation is performed using a Chromabond® Flash RS80 SiOH 40-63 μm column (Macherey-Nagel® brand). The column volume is 145 mL and the packed volume is 210 mL. Mobile phase supply will be performed using a pump with a flow rate of 5 mL / min. • Dissolve 14.6 g of soybean oil extract obtained according to Example 2 in 40 mL of heptane. The resulting solution is injected into the top of the column using a pump with a flow rate of 5 mL / min. Then, elute the column with 400 mL of heptane. Next, the column is eluted with 800 mL of heptane-dichloromethane mixture (1:1) (v / v). Furthermore, the column is eluted with 500 mL of dichloromethane. Next, the column is eluted with 500 mL of a dichloromethane-methanol mixture (1:1) (v / v). Next, elute the column with 200 mL of methanol.

[0144] 〇Protocol 2: UPLC-DAD analysis conditions • Column: BEH Shield 1.7μm C18.150*2.1mm ·Mobile phase: -A: Water + 0.1% Formic Acid -B: Acetonitrile + 0.1% Formic Acid • Gradient: Follow Table 6 below.

[0145] [Table 6]

[0146] Column temperature: 50℃ ·Flow rate: 0.4mL / min • Detection: 205nm and 234nm ·Injection volume: 1μL

[0147] 〇Protocol 3: CPG-MS analysis conditions • Column: DB-5HT (Agilent Technologies); 30m x 0.32mm x 0.1μm • Injection: 320℃; Mode = Split • Furnace: Temperature gradient (°C) according to Table 7 below

[0148] [Table 7]

[0149] • Vector gas flow rate: 1 mL / min Detection: MS transfer line temperature = 350°C; ion source temperature = 320°C; MS-EI; full scan start mass = 40; full scan end mass = 800 ·Injection volume: 1μL

[0150] Results: The obtained fractions are collected at the column outlet and analyzed by ultra-high pressure liquid chromatography (UPLC-DAD) with a diode array detector and gas chromatography (GC-MS) with a mass spectrometer. The fractions are then collected according to their composition and dried by evaporation under vacuum.

[0151] This fractionation yields four fractions, in order of decreasing polarity: triglycerides, diglycerides, monoglycerides (1-47% by mass), free fatty acids (2-11% by mass), phytosterols (3-9% by mass), and oxylipins (4-8% by mass).

[0152] These various fractions were tested according to the method of Example 5.

[0153] Table 8 summarizes the results obtained by testing the induction of total lipid production by 10 μM arachidonic acid (AA) at a concentration of 5 μg / mL for soybean oil lipid extracts prepared according to Example 2 and various fractions obtained according to Example 6.

[0154] [Table 8]

[0155] This study confirmed the strong sebum-regulating effect of soybean oil.

[0156] Free fatty acid and sterol fractions showed little to no inhibitory effect on lipid induction in sebaceous cells stimulated by arachidonic acid.

[0157] Fraction 4, which contains oxylipins, resulted in a much greater reduction in arachidonic acid-induced total lipid accumulation than the unfractionated soybean oil extract, clearly demonstrating that the oxylipin fraction (oxidized fatty acids) of the soybean oil extract can strongly inhibit arachidonic acid-induced lipid biosynthesis.

[0158] References FR2789085 Andreou et al., 2009, Lipids, 44: 207-215. Blee, 2002, Trends in Plant Science Vol 7, No.7, 315-321 Calder, 2012, J. Nutr. 142: 592S-599S Cuvelier et al., 2004, Ann. Med. Vet. 148, 133-140 Lagarde, 2011, OCL, vol 18, No.2 March-April, doi.org / 10.1051 / ocl.2011.0377 Liu et al., 2015, Brain Res. 0: 220-246 Oenel et al., 2017, Plant Cell Physiol. 58(5): 925-933 Olah et al., 2014, J. Clin. Invest. 124(9), 3713-3724. Richardson et al., 2017, J. Agric. Food Chem., 65: 1941-1951 Rusterucci et al., 1999, J Biol. Chem. Vol 274, N°51: 36446-36455 Van Ginneken et al., 2011, Lipids in Health and Disease, 10, 104

Claims

1. Oxylipin, used to treat seborrhea.

2. The oxylipin according to claim 1, wherein the seborrhea is seborrhea of ​​the skin or scalp.

3. The oxylipin according to claim 1 or 2, wherein the oxylipin is selected from octadecanoids, eicosanoids, and mixtures thereof.

4. The oxylipin is 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE), 9-hydroperoxy-10E,12Z-octadecadienoic acid (9-HpODE), 13-hydroperoxy-9Z,11E-octadecadienoic acid (13-HpODE), 9,10-dihydroxy-12Z-octadecenoic acid (9,10-DiHOME), 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME), 9,12,13-trihydroxy-10E -Octadecenoic acid (10-TriHOME), 9-keto-10E,12Z-octadecadienoic acid (9-OxoODE), 13-keto-9Z,11E-octadecadienoic acid (13-OxoODE), 9-hydroxy-10E,12Z,15Z-octadecatrienoic acid (9-HOTrE), 13-hydroxy-9Z,11E,15Z-octadecatrienoic acid (13-HOTrE), 9-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid (9-HpOTrE), 11-hydroperoxy-9Z,12Z,15Z-octadecatrienoic acid (11- HpOTrE), 12-hydroperoxy-9Z,13E,15E-octadecatrienoic acid (12-HpOTrE), 13-hydroperoxy-9Z,11E,15Z-octadecatrienoic acid (13-HpOTrE), 12,13-epoxy-9Z-octadecenoic acid (12,13-EpOME), 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid (5-HEPE), 12-hydroxy-5Z,8Z,10E,14Z,17Z-eicosapentaenoic acid (12-HEPE), 15-hydroxy-5Z,8Z,11Z,13E,17 Z-eicosapentaenoic acid (15-HEPE), 15-hydroperoxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid (15-HpEPE), 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE), 8-hydroxy-5Z,9E,11Z,14Z-eicosatetraenoic acid (8-HETE), 9-hydroxy-5Z,7E,11Z,14Z-eicosatetraenoic acid (9-HETE), 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE), 15-hydroxy-5Z,Oxylipin according to any one of claims 1 to 3, selected from 8Z,11Z,13E-eicosatetraenoic acid (15-HETE), 5-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HpETE), 11-hydroperoxy-5Z,8Z,12E,14Z-eicosatetraenoic acid (11-HpETE), 12-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HpETE), 15-hydroperoxy-5Z,8Z,11Z,13E-arachidonic acid (15-HpETE), and mixtures thereof.

5. The oxylipin according to claim 4, wherein the oxylipin is selected from 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE, 12,13-DiHOME, 15-HEPE, and mixtures thereof.

6. The oxylipin according to any one of claims 1 to 5, wherein the oxylipin is present in an extract of a plant rich in oxylipins.

7. The oxylipin according to claim 6, wherein the oily plant extract rich in oxylipins is an extract of the gametophyte of an oxylipin-rich brown alga such as apple seeds, soybeans, hazelnuts, or Saccharina latissima.

8. The oxylipin according to claim 6 or 7, wherein the oily plant extract rich in oxylipins contains at least 25% by weight, for example, at least 30% by weight, particularly at least 40% by weight, and even more particularly at least 50% by weight of oxylipins, based on the weight of the dry extract.

9. A dermatological cosmetic or dermatological composition for use in the treatment of seborrhea, comprising at least one oxylipin and at least one excipient acceptable for dermatological cosmetic or dermatological use.

10. The composition according to claim 9, wherein the seborrhea is seborrhea of ​​the skin or scalp.

11. The composition according to claim 9 or 10, wherein the at least one oxylipin is selected from octadecanoids, eicosanoids, and mixtures thereof.

12. The aforementioned at least one oxylipin is 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE), 9-hydroperoxy-10E,12Z-octadecadienoic acid (9-HpODE), 13-hydroperoxy-9Z,11E-octadecadienoic acid (13-HpODE), 9,10-dihydroxy-12Z-octadecenoic acid (9,10-DiHOME), 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME), 9,12 ,13-trihydroxy-10E-octadecenoic acid (10-TriHOME),9-keto-10E,12Z-octadecadienoic acid (9-OxoODE),13-keto-9Z,11E-octadecadienoic acid (13-OxoODE),9-hydroxy-10E,12Z,15Z-octadecatrienoic acid (9-HOTrE),13-hydroxy-9Z,11E,15Z-octadecatrienoic acid (13-HOTrE),9-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid (9-HpOTrE),11-hydroperoxy-9Z, 12Z,15Z-octadecatrienoic acid (11-HpOTrE), 12-hydroperoxy-9Z,13E,15E-octadecatrienoic acid (12-HpOTrE), 13-hydroperoxy-9Z,11E,15Z-octadecatrienoic acid (13-HpOTrE), 12,13-epoxy-9Z-octadecenoic acid (12,13-EpOME), 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid (5-HEPE), 12-hydroxy-5Z,8Z,10E,14Z,17Z-eicosapentaenoic acid (12-HE PE), 15-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid (15-HEPE), 15-hydroperoxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid (15-HpEPE), 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE), 8-hydroxy-5Z,9E,11Z,14Z-eicosatetraenoic acid (8-HETE), 9-hydroxy-5Z,7E,11Z,14Z-eicosatetraenoic acid (9-HETE), 12-hydroxy-5Z,8Z,10E,The composition according to claim 9 or 10, selected from 14Z-eicosatetraenoic acid (12-HETE), 15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-HETE), 5-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HpETE), 11-hydroperoxy-5Z,8Z,12E,14Z-eicosatetraenoic acid (11-HpETE), 12-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HpETE), 15-hydroperoxy-5Z,8Z,11Z,13E-arachidonic acid (15-HpETE), and mixtures thereof.

13. The composition according to claim 12, wherein the at least one oxylipin is selected from 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE, 12,13-DiHOME, 15-HEPE, and mixtures thereof.

14. The composition according to any one of claims 9 to 13, wherein at least one of the oxylipins is present in an oily plant extract rich in oxylipins.

15. The composition according to claim 14, wherein the oxylipin-rich oily plant extract is an extract of the gametophyte of an oxylipin-rich brown alga such as apple seeds, soybeans, hazelnuts, or Saccharina latissima.

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