Oxylipins in the treatment of seborrhea

Abstract

The present invention relates to oxylipins for use in the treatment of seborrhea, the oxylipins more particularly being present in a preferably oxylipin-enriched oleaginous plant extract. The present invention also relates to a dermo-cosmetic or dermatological composition comprising at least one oxylipin, preferably derived from an oleaginous plant, with at least one dermo-cosmetically or dermatologically acceptable excipient, for use in the treatment of seborrhea.

Description

[0001] Title: Oxylipins in the treatment of seborrhea

[0002] Technical field of the invention

[0003] The present invention relates to oxylipins, and in particular to plant extracts containing them, as well as to cosmetic or dermatological compositions comprising them, for their use in seboregulation, and in particular for the treatment of seborrhea and / or acne, preferably seborrhea.

[0004] State of the art

[0005] Living organisms are formed by one or more cells, prokaryotic or eukaryotic, whose survival, defense and proliferation functions are based on the metabolism of three large chemical families: carbohydrates, proteins and lipids.

[0006] Lipids are natural substances, and their roles are fundamental. They are major constituents of cellular structures, such as membrane phospho- and glyco-lipids. They are also reserve substances, serving as a source of energy for the body. They are involved in defense or cell signaling mechanisms and constitute coating elements such as waxes or cutins (Cuvelier et al., 2004).

[0007] Lipids are hydrophobic and sometimes amphiphilic substances, soluble in non-polar or moderately polar organic solvents.

[0008] We can distinguish simple lipids, esters of fatty acids and an alcohol which can be glycerol (constituent of triglycerides) or a high molecular mass aliphatic alcohol (constituent of cerides), from complex lipids such as phospholipids or glycolipids.

[0009] Fatty acids are the basic building blocks of lipids. They can have two additive origins in an organism: synthesis by the body and diet.

[0010] Fatty acids are aliphatic monocarboxylic acids of varying length. The most common natural fatty acids have between 4 and 28 carbon atoms. The length of their carbon chain, the number and nature of their unsaturation(s) are also variable. A distinction is made between saturated, monounsaturated (a single double bond) and polyunsaturated (several double bonds) fatty acids. Unsaturated fatty acids can contain 1 to 6 double bonds in the living kingdom. For the same chemical formula, there can be a large number of isomers, depending on the position of the double bond but also on its cis or trans conformation.

[0011] In the plant kingdom, fatty acid can be oxidized in ketonic form (e.g. licinic acid), hydroxylated form (e.g. ricinoleic acid) or in epoxy form (e.g. vernolic acid).

[0012] In general, triglycerides are heterogeneous and a vegetable oil is a complex mixture of triesters. In the plant world, triacylglycerols are generally stored in the form of oily inclusions (oleosomes from the endoplasmic reticulum) which sometimes coalesce into large clusters in the cells of storage tissues. This is particularly true in seeds where they can represent more than 50% of the dry mass. Exceptionally, the seed may accumulate not triglycerides, but esters of fatty acids and long-chain aliphatic alcohols (e.g. jojoba). Although this is less common, there are fruits that concentrate triglycerides in their pericarp (olive, avocado, bay berry, etc.).

[0013] Omega 3 and Omega 6, essential in 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 enzymatic arsenal of vertebrates without the essential supply of linoleic acid and alpha-linolenic acid. These nutrients are therefore considered vital and must be provided by the diet. These polyunsaturated fatty acids are mainly present in the diet in the form of triacylglycerols, sterol esters, phospholipids, esterified or not or in free form (Liu et al., 2015). Among the main plant sources of linoleic acid, we can cite soybean, sunflower, safflower, evening primrose, and rice bran oils.

[0014] Among the main plant sources of alpha-linolenic acid are rapeseed, flax, camelina, chia, canola, soybean, perilla and walnut oils.

[0015] Several oleaginous macroalgae and microalgae are also sources of polyunsaturated fatty acids (Van Ginneken et al., 2011).

[0016] Polyunsaturated fatty acids are the substrate for numerous enzymatic and non-enzymatic reactions that produce oxygenated metabolites with diverse functions called oxylipins. Oxylipins include oxidized polyunsaturated fatty acids and their derivatives. They are present in mammals, flowering plants (angiosperms), mosses, algae, bacteria, and fungi. Oxylipins include signaling molecules, ligands for transcription factors, and precursors for the synthesis of lipid mediators (Calder, 2012). For example, the eicosanoid class, which includes leukotrienes and prostanoids, is a large family of oxidation derivatives of 20-carbon polyunsaturated fatty acids. Docosanoids are enzymatic oxidation products of 22-carbon polyunsaturated fatty acids such as docosahexaenoic acid.Oxidation products of 18-carbon polyunsaturated fatty acids such as linoleic acid or gamma-linolenic acid belong to the octadecanoid class. Octadecanoids derived from linoleic acid include 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE). These two molecules are described as an in vivo oxidation marker (Lagarde, 2011). Hydroperoxy, epoxy, or ketonic forms derived from linoleic acid are also documented (Richardson et al., 2017). The best-known oxygenated metabolite of gamma-linolenic acid is the one leading to jasmonic acid, a cyclic derivative with well-described phytopathogen resistance activities (Blée, 2002).

[0017] The oxidation of polyunsaturated fatty acids can be carried out by non-enzymatic as well as enzymatic pathways (Oenel et al., 2017). For the latter, the position of the unsaturations on the polyunsaturated fatty acid as well as the enzymatic environment will define the type of oxylipins formed. The main pathways are those of cyclooxygenases, lipoxygenases and cytochrome P-450 (Andreou et al., 2009). While the enzymatic pathway appears to be the main pathway for the formation of oxygenated fatty acids from polyunsaturated fatty acids in free form, some studies show that the oxidation of polyunsaturated fatty acids, particularly in their esterified form (triglycerides in particular), can be carried out by non-enzymatic pathways. This can occur in the oleaginous plant matrix by the action of free radicals, the formation of which can be favored by storage conditions (temperature, duration, etc.).These oxidized fatty acids can then be released after deesterification, notably through the action of lipases (Oenel et al., 2017).

[0018] Oxylipins are present in polyunsaturated vegetable oils or oleaginous plant matrices with polyunsaturated fatty acids from plants or algae. Algae can indeed be sources of polyunsaturated fatty acids and contain the enzymes allowing the formation of oxylipins (Richardson et al., 2017). Their synthesis can also be promoted in low-oleaginous tissues under certain conditions, such as tobacco leaves exposed to cryptogein (Rustérucci et al., 1999). Finally, patent application FR2789085 describes a process for obtaining an oil enriched in hydroxyoctadecadienoic fatty acids and in particular in 9-hydroxyoctadecadienoic acid from an oily mixture containing linoleic acid.Hydroxyoctadecadienoic fatty acids are obtained by controlled oxidation of linoleic acid and / or alpha and / or gamma linolenic acid or their esters in the presence of an oxidation catalyst such as iron or copper halide.

[0019] The sebaceous gland is an exocrine gland present on all of the skin, with the exception of the palms of the hands and feet. It is found more particularly in the seborrheic regions of the face, especially in the T-zone, that is to say the middle area of ​​the face which forms a T, the back and the torso. It is generally associated with a hair follicle. This is why we speak of the pilosebaceous unit. The sebaceous gland is responsible for the synthesis and secretion of sebum by sebocytes, epithelial cells which compose it.

[0020] Sebum is a complex of lipids synthesized under hormonal stimulation. It is an essential component of the hydrolipidic film that protects the skin from external aggressions and dehydration by playing a major role as a barrier. Associated with this barrier function, sebum also has antibacterial properties, via oleic and palmitoleic acids and an antioxidant power notably provided by vitamin E. Thus, sebum helps maintain the integrity of the skin barrier.

[0021] Seborrhea is an excessive secretion of sebum by the sebaceous glands. It causes aesthetic problems. Regarding the skin, it has a shiny appearance, the complexion is dull and the pilosebaceous orifices are dilated. In addition, makeup does not hold well on this type of so-called oily skin. For seborrhea of ​​the scalp, the hair has a greasy and dull appearance and is difficult to style. When seborrhea is intense, it is said to be oily, fluent and it can be associated with a rancid odor.

[0022] Acne is a chronic inflammatory skin condition of this pilosebaceous unit leading to the formation of retentional lesions, i.e. open and / or closed comedones. It is important not to trivialize this condition and to treat it correctly because it can lead to disabling psychosocial consequences, particularly due to the formation of scars.

[0023] During acne, under the influence of various endogenous factors, mainly hormonal, but also external factors such as pollution, poor diet, stress, etc., there is a deregulation of the sebaceous gland affecting the quantity and quality of sebum. Indeed, the skin of acne patients is characterized by an increase in sebum secretion, called hyperseborrhea, as well as a change in its overall composition called dysseborrhea. The lipid ratios present in the sebum from subjects with acne differ from the sebum from healthy skin, with in particular a significant increase in the levels of free fatty acids, squalene and its oxidation, and waxes.

[0024] This modified hyperseborrhea, that is to say more sebum and thicker consistency, will participate, with dyskeratosis, in the obstruction of the follicular canal. In addition, it will constitute a favorable culture medium for the development of pro-inflammatory acne bacteria, such as Cutibacterium acnes, the most described to date. All of these elements will therefore be at the origin of the appearance of the first acne lesions, open and closed comedones, which can evolve into more severe inflammatory lesions, papules, pustules and nodules.

[0025] Thus, there is still a need to provide effective solutions for treating seborrhea, and therefore also acne, and resolving the aesthetic inconveniences associated with seborrhea. Summary of the invention

[0026] The present invention therefore aims to meet these needs. Indeed, the inventors have surprisingly demonstrated that extracts enriched with oxylipins from different plants have the capacity to reduce sebum production. Such anti-seborrheic activity is particularly interesting in patients with acne-prone skin.

[0027] The present invention thus relates to at least one oxylipin, and more particularly a mixture of oxylipins such as a plant extract containing or enriched in oxylipins, for its use in the treatment of seborrhea and / or acne, preferably seborrhea.

[0028] The invention also relates to the use of at least one oxylipin, and more particularly a mixture of oxylipins such as a plant extract containing or enriched with oxylipins, for the preparation of a dermo-cosmetic or dermatological composition intended for the treatment of seborrhea and / or acne, preferably seborrhea.

[0029] The invention also relates to the use of at least one oxylipin, and more particularly a mixture of oxylipins such as a plant extract containing or enriched in oxylipins, for the treatment of seborrhea and / or acne, preferably seborrhea.

[0030] The invention also relates to a method of treating seborrhea and / or acne, preferably seborrhea, comprising administering to a person in need thereof an effective amount of at least one oxylipin, and more particularly a mixture of oxylipins such as a plant extract containing or enriched in oxylipins.

[0031] The present invention also relates to a dermo-cosmetic or dermatological composition comprising at least one oxylipin, and more particularly a mixture of oxylipins such as a plant extract containing or enriched with oxylipins, with at least one dermo-cosmetically or dermatologically acceptable excipient, for its use in the treatment of seborrhea and / or acne, preferably seborrhea.

[0032] The invention also relates to the use of a dermo-cosmetic or dermatological composition comprising at least one oxylipin, and more particularly a mixture of oxylipins such as a plant extract containing or enriched with oxylipins, with at least one dermo-cosmetically or dermatologically acceptable excipient, for the preparation of a medicament intended for the treatment of seborrhea and / or acne, preferably seborrhea.

[0033] The invention also relates to a method for treating seborrhea and / or acne, preferably seborrhea, comprising administering to a person in need thereof an effective amount of a dermo-cosmetic or dermatological composition comprising at least one oxylipin, and more particularly a mixture of oxylipins such as a plant extract containing or enriched in oxylipins, with at least one dermo-cosmetic or dermatologically acceptable excipient.

[0034] In the context of the present invention, the oxylipin may preferably be a mixture of oxylipins. The oxylipin will more particularly be derived from a plant and more particularly from an oleaginous plant material and may be present in a plant extract, and more particularly a plant extract enriched in oxylipins. The plant extract may more particularly be an oleaginous plant extract, preferably enriched in oxylipins.

[0035] Definitions

[0036] For the purposes of the present invention, the term "approximately" means that the value concerned may be 10% lower or higher, in particular 5%, in particular 2%, more particularly 1% lower than the indicated value.

[0037] For the purposes of the present invention, the term "extract" or "plant extract" or "plant extract" means the product obtained after extraction of the plant or a part of the plant, such as a vegetable oil from the plant, with a solvent called an extraction solvent, which may then optionally be in a concentrated or dry form after partial or total evaporation of the extraction solvent. In particular, it may be a dry extract. Extraction may also be carried out by mechanical methods such as pressure.

[0038] For the purposes of the present invention, the term "dry extract" means an extract without extraction solvent, or containing only insignificant traces thereof. Such a dry extract thus contains only material derived from the plant raw material. It may also contain insignificant traces of extraction solvent.

[0039] For the purposes of the present invention, the term "oleaginous plant material" means an oleaginous plant or part of a plant, i.e. one rich in fats. This may be, for example, oleaginous seeds or fruits (e.g. apple seeds, soybeans, flax seeds, safflower seeds, cumin seeds, camelina seeds, canola seeds, perilla seeds, chia seeds, rapeseed seeds, hazelnuts or a mixture thereof), gametophytes (e.g. brown algae, in particular Saccharina latissimà) or a mixture thereof. It may also be a vegetable oil (e.g. 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 a mixture of these).

[0040] For the purposes of the present invention, the term “oleaginous plant extract” means an extract as defined above obtained from an oleaginous plant material.

[0041] For the purposes of the present invention, the term "fatty acid" means a RICO2H carboxylic acid whose chain R1 is a linear or branched hydrocarbon chain, saturated or comprising one or more, in particular 1, 2, 3, 4, 5 or 6, C=C double bonds, the carboxylic acid comprising from 10 to 28, preferably from 14 to 24, in particular from 16 to 22, carbon atoms (including the carbon atom of the carboxylic acid function).

[0042] For the purposes of the present invention, the term "polyunsaturated fatty acid" means a fatty acid as defined above whose hydrocarbon chain comprises one or more, in particular 1, 2, 3, 4, 5 or 6, C=C double bonds.

[0043] For the purposes of the present invention, the term "free fatty acid" means a fatty acid not bound to other molecules (for example to glycerol or derivatives thereof to give glycerides or to an alcohol to give a fatty ester).

[0044] For the purposes of the present invention, the term "oxylipin" means an oxygenated molecule resulting from the enzymatic or non-enzymatic oxidation of polyunsaturated fatty acids. The oxidation of polyunsaturated fatty acid makes it possible in particular to introduce one or more, in particular 1, 2 or 3, oxygenated groups chosen in particular from hydroxy (-OH), hydroperoxy (-OOH), keto (=0; the oxygen being linked by a double bond to a carbon atom) and epoxy (-0-; the oxygen being linked to two adjacent carbon atoms) groups, preferably 2 or 3 hydroxy and / or keto groups, in particular with displacement of one or more, in particular 1, 2 or 3, C=C double bonds so as to create a conjugation with another double bond and / or replacement of a C=C unit by a C(GO1)-C(GO2) unit where G01 and G02 each represent, independently of one another, an oxygenated group as defined above.Oxylipins can be in particular an octadecanoid, an eicosanoid or a mixture of these.

[0045] For the purposes of the present invention, the term "octadecanoid" means an oxygenated molecule resulting from the enzymatic or non-enzymatic oxidation of a polyunsaturated fatty acid with 18 carbon atoms as defined above, the polyunsaturated fatty acid with 18 carbon atoms possibly being, for example, linoleic acid, alpha-linolenic acid, gamma-linolenic acid or stearidonic acid, preferably linoleic acid, alpha-linolenic acid or gamma-linolenic acid. These may be 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11 E-octadecadienoic acid (13-HODE), 9-hydroperoxy- 10E,12Z-octadecadienoic acid (9-HpODE), 13-hydroperoxy-9Z,11 E-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 acid,11 E-octadecadienoic acid (13-OxoODE), 9-hydroxy-10E,12Z,15Z-octadecatrienoic acid (9-HOTrE), 13-hydroxy-9Z,11 E,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,11 E,15Z- octadecatrienoic acid (13-HpOTrE), 12,13-epoxy-9Z-octadecenoic acid (12,13-EpOME), or a mixture thereof.,

[0046] For the purposes of the present invention, the term "eicosanoid" means an oxygenated molecule resulting from the enzymatic or non-enzymatic oxidation of a polyunsaturated fatty acid with 20 carbon atoms as defined above, the polyunsaturated fatty acid with 20 carbon atoms possibly being, for example, arachidonic acid or eicosapentaenoic acid. These may be 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), 9-hydroxy-5Z,7E,11Z,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), acid 15-hydroperoxy-5Z,8Z,11Z,13E-arachidonic acid (15-HpETE), or a mixture thereof.

[0047] For the purposes of the present invention, the term "oxylipin-enriched extract" means an extract as defined above obtained from a plant or a part thereof containing oxylipins, and the synthesis of which in oxylipins has been stimulated, or an extract as defined above which has been subjected to a step of enrichment in oxylipins (e.g. by chromatography).

[0048] For the purposes of the present invention, the term "apolar solvent" means a lipophilic solvent for solubilizing compounds of low polarity, i.e. having a LogP greater than or equal to 1, chosen for example from heptane, hexane, limonene, chloroform, dichloromethane, supercritical CO2, a supercritical CO2 / ethanol mixture and mixtures of these solvents. Mention may also be made of 100% bio-sourced lipophilic solvents such as, for example, EcoXtract® LIPOCOS (Supplier Pennakem Europa).

[0049] For the purposes of the present invention, the term "hydrophilic solvent" means a polar solvent chosen, for example, from water, subcritical water, water-miscible alcohols such as, for example, C1 to C3 alcohols, C3 to C5 glycols, glycerol, acetone, and mixtures thereof.

[0050] For the purposes of the present invention, the term "organic solvent immiscible with a vegetable oil" means an organic solvent which is not capable of mixing, or only partially, with the vegetable oil, so that the mixture of the organic solvent and the vegetable oil gives a heterogeneous mixture in which at least two distinct phases can be observed.

[0051] For the purposes of the present invention, the term "C1 to C3 alcohol" means an alcohol R2OH whose chain R2 is a saturated, linear or branched hydrocarbon chain comprising 1 to 3 carbon atoms. It may be methanol, ethanol, n-propanol or isopropanol, in particular methanol, ethanol or isopropanol. Preferably, it will be ethanol.

[0052] For the purposes of the present invention, the term "C3 to C5 glycol" means a saturated, linear or branched hydrocarbon chain comprising 3 to 5 carbon atoms, said chain carrying 2 OH functions. Examples include propylene glycol.

[0053] For the purposes of the present invention, "room temperature" means a temperature between 15 and 40°C, preferably between 20 and 30°C, in particular around 25°C.

[0054] Detailed description of the invention

[0055] The invention relates to an oxylipin, including a mixture of oxylipins which may be in the form of a plant extract containing or enriched in oxylipins, for use in the treatment of seborrhea and / or acne, preferably seborrhea. Seborrhea may be seborrhea of ​​the skin or of the scalp.

[0056] Oxylipin is as defined above and may in particular be chosen from octadecanoids, eicosanoids and mixtures thereof. Thus, the oxylipin may be selected from 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11 E-octadecadienoic acid (13-HODE), 9-hydroperoxy-10E,12Z-octadecadienoic acid (9-HpODE), 13-hydroperoxy-9Z,11 E-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,11 E-octadecadienoic acid (13-OxoODE), 9-hydroxy-10E,12Z,15Z-octadecatrienoic acid (9-HOTrE), 13-hydroxy-9Z,11 E,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,11 E,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,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 a mixture thereof.,

[0057] According to a particular embodiment, the oxylipin is chosen from 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE, 12,13-DiHOME, 15-HEPE and mixtures thereof.

[0058] The oxylipin is preferably present in a plant extract, preferably a plant extract enriched in oxylipins. The plant extract will contain at least one oxylipin as defined above, in particular at least one oxylipin chosen from 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE, 12,13-DiHOME, 15-HEPE and mixtures thereof. The plant extract may more particularly be an oleaginous plant extract, preferably enriched in oxylipins, which may be obtained from different oleaginous plant materials.

[0059] Oleaginous plant material is an oleaginous plant or part of an oleaginous plant, i.e. rich in fat, and more particularly in vegetable oil containing polyunsaturated fatty acids. The oleaginous plant material may therefore be, for example, a vegetable oil containing polyunsaturated fatty acids. The oleaginous plant material may also be gametophytes, preferably containing polyunsaturated fatty acids.

[0060] The vegetable oil containing polyunsaturated fatty acids will more particularly contain polyunsaturated fatty acids with 18 carbon atoms (C18) such as linoleic acid, alpha-linolenic acid or gamma-linolenic acid; polyunsaturated fatty acids with 20 carbon atoms (C20) such as arachidonic acid or eicosapentaenoic acid; or a mixture thereof. Preferably, the content of polyunsaturated fatty acids in the vegetable oil is at least 10%, preferably at least 40% by weight relative to the total fatty acid weight of the vegetable oil. Preferably, the content of C18 and / or C20 polyunsaturated fatty acids in the vegetable oil is at least 15%, preferably at least 40% by weight relative to the total fatty acid weight of the vegetable oil.

[0061] The vegetable oil containing polyunsaturated fatty acids may be, 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 a mixture thereof. The gametophytes may be gametophytes of brown algae such as Saccharina latissima. The oleaginous plant extract, preferably enriched with oxylipins, will more particularly be an apple seed extract (more particularly apple seed oil), a soybean seed extract (more particularly soybean oil), a hazelnut extract (more particularly hazelnut oil), or an extract of gametophytes of brown algae such as Saccharina latissima, said extract therefore containing oxylipins, and preferably being enriched with oxylipins.

[0062] Preferably, the oleaginous plant extract will not be a hazelnut extract such as hazelnut oil.

[0063] According to a particular embodiment of the invention, the synthesis of oxylipins can be stimulated in the plant or a part thereof (e.g. a vegetable oil or gametophytes), before extraction of the plant or a part thereof. This means that the growth or cultivation parameters of the plant or a part thereof are modified so as to stimulate the synthesis of oxylipins in the plant or a part thereof and therefore to increase the oxylipin content in the plant or a part thereof.

[0064] The synthesis of oxylipins can be stimulated in the plant or part of it, for example, by optimizing the parameters favoring oxidation processes, such as temperature, or by enzymatic treatment.

[0065] Oxylipin synthesis can also be stimulated by elicitation, particularly in plant cell cultures, for example gametocytes.

[0066] According to another embodiment, the plant extract may be enriched in oxylipins, for example by molecular distillation of the extract and / or by fractionation of the extract, in particular by chromatographic techniques. The synthesis of oxylipins may have been stimulated in the plant or a part thereof as described above, before extraction of the plant or a part thereof.

[0067] When the plant or part thereof is a vegetable oil containing polyunsaturated fatty acids (hereinafter referred to as "vegetable oil"), the vegetable oil may be obtained by pressing the oleaginous vegetable raw material (e.g. seeds, pips, etc.), in particular by cold pressing, i.e. without heating, at room temperature, preferably followed by a filtration step.

[0068] Vegetable oil can also be obtained by extraction of the oleaginous plant raw material (e.g. seeds, pips, etc.), whole or ground, with a non-polar solvent. Such extraction can be carried out with supercritical CO2, with or without the addition of ethanol as a co-solvent, and optionally followed by a filtration step. Vegetable oil can also be obtained by extraction of the oleaginous plant raw material with a hydrophilic solvent in the presence of at least one enzyme (e.g. pectinase), and in particular an enzymatic mixture such as pectinases for example.

[0069] Preferably, the vegetable oil will be obtained by pressing the oleaginous vegetable raw material, in particular by cold pressing, i.e. without heating, at room temperature, preferably followed by a filtration step.

[0070] The oleaginous plant extract can be obtained from vegetable oil, by extraction with a hydrotropic aqueous solution, subcritical water or an organic solvent immiscible with vegetable oil optionally in mixture with water. The oleaginous plant extract can be enriched in oxylipins, for example by molecular distillation of the extract, or by fractionation of the extract by techniques.

[0071] The organic solvent immiscible with vegetable oil may be used in a mixture with water, in particular in an organic solvent / water volume ratio of between 80 / 20 and 100 / 0, in particular between 85 / 15 and 95 / 5, in particular approximately 90 / 10.

[0072] The organic solvent immiscible with vegetable oil may in particular be a C1 to C3 alcohol, possibly mixed with water, in particular in the organic solvent / water volume ratio described above. The C1 to C3 alcohol will more particularly be methanol, ethanol, n-propanol or isopropanol, in particular methanol, ethanol or isopropanol, preferably ethanol.

[0073] The extraction solvent may in particular be chosen from methanol, a methanol / water mixture, ethanol, an ethanol / water mixture, isopropanol and an isopropanol / water mixture. According to a preferred embodiment, the extraction solvent will be methanol, an ethanol / water mixture in a volume ratio of approximately 90 / 10 or an isopropanol / water mixture in a volume ratio of approximately 90 / 10.

[0074] According to a preferred embodiment, the oleaginous plant extract can be obtained by a process according to the invention described below.

[0075] A process for preparing an oleaginous plant extract comprises a step of extracting a vegetable oil using an extraction solvent comprising, in particular consisting of, a hydrotropic aqueous solution, subcritical water, or an organic solvent immiscible with the vegetable oil, optionally mixed with water.

[0076] According to a particular embodiment, the extraction solvent comprises, in particular is constituted by, an organic solvent immiscible with vegetable oil, optionally mixed with water.

[0077] The organic solvent immiscible with vegetable oil may be, in particular, a C1 to C3 alcohol. The extraction solvent may be, in particular, a C1 to C3 alcohol, possibly mixed with water.

[0078] The C1 to C3 alcohol may be methanol, ethanol, n-propanol or isopropanol, in particular methanol, ethanol or isopropanol. Preferably, it will be ethanol.

[0079] The organic solvent immiscible with vegetable oil, in particular a C1 to C3 alcohol such as methanol, ethanol or isopropanol, may be used in a mixture with water, in particular in an organic solvent / water volume ratio of between 80 / 20 and 100 / 0, in particular of between 85 / 15 and 95 / 5, in particular of approximately 90 / 10.

[0080] The extraction solvent may in particular be chosen from methanol, a methanol / water mixture, ethanol, an ethanol / water mixture, isopropanol and an isopropanol / water mixture.

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

[0082] The vegetable oil extraction step will be carried out in particular by mixing the vegetable oil with the extraction solvent for 1 to 12 hours and in particular at a temperature of between 15 and 25°C, in particular around 20°C. The quantity of extraction solvent used to carry out this extraction will advantageously be 0.5 to 3 g, in particular 1 to 3 g per 1 g of vegetable oil.

[0083] An extraction phase and a lipid phase will then be obtained at the end of this extraction. The extraction phase will advantageously be separated from the lipid phase and recovered before being dried, partially or totally, in particular under vacuum, to remove more or less the extraction solvent and obtain either the dry extract if the solvent is completely removed, or the concentrated extract which is diluted in residual solvent.

[0084] According to one embodiment of the invention, the method of the invention will comprise the following two successive steps:

[0085] 1. obtaining a vegetable oil, and

[0086] 2. extraction of vegetable oil with an extraction solvent, comprising, in particular consisting of, a hydrotropic aqueous solution, subcritical water or an organic solvent immiscible with vegetable oil, optionally mixed with water.

[0087] According to a preferred embodiment according to the invention, the method according to the invention will comprise the following successive steps:

[0088] 1. possibly obtaining a vegetable oil,

[0089] 2. extraction of vegetable oil with an extraction solvent, comprising, in particular consisting of, a hydrotropic aqueous solution, subcritical water or an organic solvent immiscible with the oil from vegetable achenes, optionally mixed with water, to give an extraction phase and a lipid phase,

[0090] 3. recovery of the extraction phase obtained in step (2), and

[0091] 4. partial or total drying of the extraction phase to give a concentrated or dry extract according to the invention.

[0092] Step (1) can be carried out by pressing the oleaginous plant raw material (e.g. seeds, pips, etc.), in particular by cold pressing, i.e. without heating, at room temperature, preferably followed by a filtration step.

[0093] Step (2) will advantageously be carried out with an extraction solvent as defined previously.

[0094] The extraction solvent may be methanol, ethanol or isopropanol, optionally mixed with water, in particular in an organic solvent / water volume ratio of between 80 / 20 and 100 / 0, in particular between 85 / 15 and 95 / 5, in particular approximately 90 / 10. An advantageous extraction solvent is an ethanol / water mixture in a volume ratio of approximately 90 / 10.

[0095] The extraction step (2) may be carried out by mixing vegetable oil with the extraction solvent for 1 to 12 hours and in particular at a temperature of 15 to 25°C, in particular approximately 20°C. The quantity of extraction solvent used to carry out this extraction will advantageously be 0.5 to 3 g, in particular 1 to 3 g per 1 g of vegetable oil. This extraction step (2) makes it possible to obtain at the end an extraction phase of interest and a lipid phase. Step (3) will advantageously be carried out by separating the extraction phase from the lipid phase.

[0096] Step (4) will advantageously be carried out under vacuum.

[0097] The oxylipin-enriched extract will in particular contain 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 relative to the weight of dry extract. The oxylipin-enriched extract may comprise up to 100% by weight of oxylipins.

[0098] The present invention also relates to a dermo-cosmetic or dermatological composition comprising at least one oxylipin as described above, with at least one dermo-cosmetically or dermatologically acceptable excipient, for the treatment of seborrhea and / or acne, preferably seborrhea. Seborrhea may be seborrhea of ​​the skin or even of the scalp. The oxylipin will no longer be particularly derived from a plant and more particularly from an oleaginous plant material and may be present in a plant extract as defined above, and more particularly a plant extract enriched in oxylipins. The plant extract may more particularly be an oleaginous plant extract as defined above, preferably enriched in oxylipins.The oleaginous plant extract will more particularly be an apple seed extract (more particularly apple seed oil), a soybean seed extract (more particularly soybean oil), a hazelnut extract (more particularly hazelnut oil), or an extract of gametophytes of brown algae such as Saccharina latissima, said extract therefore containing oxylipins.

[0099] The dermo-cosmetic or dermatological composition according to the invention is typically in a form suitable for topical use. The dermo-cosmetic or dermatological composition according to the invention is therefore not intended to be rinsed off after application (typically, the skin is not rinsed or washed for at least 12 hours after application of the composition). The dermo-cosmetic or dermatological compositions may be in the forms which are usually known for topical administration, i.e. in particular lotions, milks, emulsions, serums, balms, masks, creams, dispersions, gels, mousses, sprays, shampoos.

[0100] Dermo-cosmetic or dermatological compositions may also contain surfactants, complexing agents, preservatives, antioxidants such as tocopherols, stabilizing agents, emulsifiers, thickeners, gelling agents, humectants, emollients, trace elements, essential oils, perfumes, colorants, matting agents, chemical or mineral filters, moisturizing agents, thermal waters, etc.

[0101] The following examples, as well as the figures, illustrate the invention without limiting its scope.

[0102] Figures

[0103] Figure 1: HPLC (high performance liquid chromatography) chromatogram of a lipid extract of Saccharina latissima gametophytes (UV 236nm) showing the presence of molecules with the characteristic UV signature of oxylipins, and in particular 12(S)-HEPE and 15(S)-HEPE. The oxylipin 15(S)HEPE is the most abundant.

[0104] Figure 2: Oxylipin production of Saccharina latissima gametophytes suspended in a culture medium for 48 hours without (control) or with the addition of phosphates (K2HPO4 75mg / L +p-glycerophosphate Na2 x H2O 50mg / L) and / or iron Fe 3+ (FeCh.ô W 0.91 mg / L) in the culture medium. The oxylipin contents are expressed in mg 15(S)HEPE equivalent per liter of suspension. Figure 3: Evolution over time of the quantities of oxylipins produced (in mg 15(S)HEPE equivalent) per liter of culture medium for cultures A (control) and B (phosphate-enriched culture medium).

[0105] Figure 4: Evolution over time of the quantities of oxylipins (in mg equivalent 15(S)HEPE) produced per liter of culture medium for culture A (control) and culture B (elicited in phosphate and iron). Elicitation (indicated by an arrow) is carried out on the 34th day of culture by the addition of phosphates (K2HPO4 75mg / L + p-glycerophosphate Na2 x H2O 50mg / L) and iron Fe 3+ (FeCh.ô W 1 mg / L) in the culture medium.

[0106] Examples

[0107] Example 1: Lipid extract obtained from apple seed oil

[0108] The lipid extract was obtained as follows:

[0109] • Cold pressing of apple seeds (Pyrus malus L.) to obtain an apple seed oil whose fatty acid cut shows a content of 50% by weight in linoleic acid;

[0110] • Extraction of apple seed oil using an ethanol / water mixture (90 / 10 v / v) with 2 grams of the ethanol / water mixture per gram of oil for 2 hours at 20C;

[0111] • Recovery of the ethanolic phase, and evaporation of the solvent under vacuum to obtain a lipid extract.

[0112] The lipid extract was obtained with an extraction mass yield of approximately 1% and whose main octadecanoids are 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE and 9-OxoODE.

[0113] Example 2: Lipid extract obtained from soybean oil

[0114] The lipid extract was obtained as follows:

[0115] • Cold pressing of soybeans (Glycine max (L.) Merr.) to obtain a soybean oil whose fatty acid cut shows a content of 55% linoleic acid and 8% alpha-linolenic acid;

[0116] • Extraction of soybean oil by an ethanol / water mixture (90 / 10 v / v) with 2 grams of the ethanol / water mixture per gram of oil for 2 hours at 20C;

[0117] • Recovery of the ethanolic phase, and evaporation of the solvent under vacuum to obtain a lipid extract.

[0118] The lipid extract was obtained with an extraction mass yield of approximately 5.5% and whose main octadecanoids are 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE and 9-OxoODE. Example 3: Lipid extract obtained from hazelnut oil

[0119] The lipid extract was obtained as follows:

[0120] • Cold pressing of shelled hazelnuts (Corylus avellana L.) to obtain a hazelnut oil whose fatty acid cut shows a content of 15% linoleic acid;

[0121] • Extraction of hazelnut oil using an ethanol / water mixture (90 / 10 v / v) with 2 grams of the ethanol / water mixture per gram of oil for 2 hours at 20C;

[0122] • Recovery of the ethanolic phase, and evaporation of the solvent under vacuum to obtain a lipid extract.

[0123] The lipid extract was obtained with an extraction mass yield of approximately 1.5% and whose main octadecanoids are 10-TriHOME, 13-HODE, 9-HODE, and 12,13-DiHOME.

[0124] Example 4: Lipid extract obtained from Saccharina latissima

[0125] 4a: Experiment in a culture medium with or without the addition of phosphates and / or ferric iron

[0126] A male gametophyte strain of Saccharina latissima is cultured in reconstituted seawater. Biomass cultures are carried out in a bioreactor at 18 °C with a supply of CO2-enriched air to maintain a pH of 8.0 and agitation by pneumatic stirring of the suspension. The culture is illuminated by light-emitting diodes over a 16 / 8 h photoperiod. Once the biomass has reached a critical density, the gametophyte biomass is collected on nylon sieves and is lyophilized under vacuum just before a solid / liquid extraction. This is done by grinding in the presence of solvent (e.g. an ethanol / methyl ethyl ketone mixture 52:48 (v / v)). Grinding is carried out using a vibrating mill (Retsch MM 400) or alternatively an ultrasonic mill (Branson, Digital Bonifier 450). Between each grinding, the tubes containing the biomass are centrifuged at 8000g for 10 minutes.The clarified supernatants are collected and then new solvent is introduced into the grinding tubes containing the biomass pellets for a second repetition of the grinding steps. The collected supernatant fractions undergo a decolorization step. For this, the fractions are diluted in purified water and incubated at 4°C in the dark. Then the tubes are centrifuged and the decolorized supernatants are collected. Then a support solvent (DMSO, Penthylene glycol, Eutanol® G...) is placed in the decolorized fractions in order to ensure a final dry matter titer after complete evaporation of the solvents and water to leave only the dry matter solubilized in the chosen support. The analysis is done by HPLC (Waters Alliance Chain 2695 controlled by Empower Ver 2 software.03 equipped with a WATERS 2996 diode array detector) using a CORTECS C8 2.7 p 4.6 x 150 mm column equipped with a CORTECS C8 2.7 p 3.9 x 5 mm VG guard column inserted in an oven at 35 °C. The mobile phases are A = distilled water with 0.1% formic acid; B = acetonitrile with 0.1% formic acid; C = methanol with 0.1% formic acid. The flow rate is 0.7 ml / min with the following gradient: 1.5 min 50% A, 50% B; 22 min 30% A, 70% B; 25 min 30% A, 70% B; 25.1 min 100% C; 29 min 100% C; 29.1 min 50% A, 50% B; 35 min 50% A, 50% B. UV detection is performed at 236.5 nm. The device is calibrated by successive injections of a 15(S)-HEPE (Cayman chemical) solution at 10 mg / L, giving a linear correlation between the detected areas and the analyzed quantities.

[0127] The chromatograms show the presence of several isomers and derived oxylipins with the characteristic UV signature of oxylipins identical to that of 15(S)-HEPE (Figure 1). These form peaks with retention times ranging from 10 minutes to 30 minutes and the oxylipin 15(S)-HEPE, which has the most abundant peak, has a retention time of 13 minutes. The oxylipin content is expressed in pg 15(S)-HEPE equivalents by summing the peak areas of 15(S)-HEPE and isomers and derived oxylipins.

[0128] Analysis of samples from control and elicited biomasses after addition of phosphates (K2HPO4 75mg / L +p-glycerophosphate Na2 x H2O 50mg / L) and / or iron Fe 3+ (FeCh.ô W 0.91 mg / L) in the culture medium allowed to observe that the overall production of oxylipins per liter of suspension from the control culture is 0.23 mg / L while the cultures elicited using phosphates or ferric iron (Fe 3+) have similar overall oxylipin productions of the order of 0.46 mg / L. The addition of phosphates and ferric iron simultaneously allows us to observe overall oxylipin productions per liter of suspension of 0.58 mg / L (Figure 2).

[0129] 4b: Experiment of elicitation of culture in bioreactor by addition of phosphates at the start of culture

[0130] A male gametophyte culture of Saccharina latissima is carried out in a 10L bioreactor for 63 days. 5L of this culture is transferred to another bioreactor in order to carry out two parallel cultures A and B. Both cultures A and B receive 5L of new medium previously sterilized and cooled. An additional addition of phosphates is made only in culture B. Thus the phosphate concentrations are for culture A 37.5mg / L of K2HPO4 and 25mg / L of P-glycerophosphate Na2 x H2O provided by the culture medium and for culture B 112.5mg / L of K2HPO4 and 75mg / L of P-glycerophosphate Na2 x H2O provided by the culture medium and the additional addition. The two cultures are then carried out identically with the same lighting, temperature and pH regulation conditions. The biomasses are harvested and then frozen at -20°C at regular intervals.HPLC analysis of total oxylipins expressed in mg of 15(S)-HEPE equivalent per liter of culture shows that from 10. ème day of culture, the contents of the culture having received the most phosphates (B) are higher than those of the control culture (A), this difference is at its peak on the 15th ème culture day (Figure 3).

[0131] 4c: Experiment of elicitation of culture in bioreactor by addition of phosphates and iron during culture

[0132] A male gametophyte culture of Saccharina latissima is carried out in a 10L bioreactor for 63 days. 5L of this culture is transferred to another bioreactor in order to carry out two parallel cultures A and B. Both cultures A and B receive 5L of new medium previously sterilized and cooled. The two cultures are then carried out in an identical manner for 34 days with the same lighting, temperature and pH regulation conditions. Phosphates and ferric iron are added at 34 ème day only in culture B (elicited culture) by the addition of 75mg / L of K2HPO4, 50mg / L of p-glycerophosphate Na2 x H2O and 1mg / L of FeCh.ôfW. The biomasses are harvested then frozen at -20°C at regular intervals. HPLC analysis of total oxylipins expressed in mg of 15(S)-HEPE equivalent per liter of culture shows that from the 36 èmeday, or 48 hours after Congratulation, the contents of the culture having received Congratulation (B) are higher than those of the control culture (A), this difference is observable until the end of the experiment (Figure 4).

[0133] Example 5: Effects of different plant extracts containing oxylipins on arachidonic acid-induced lipogenesis in sebocytes

[0134] Sebocytes are the predominant cell type in sebaceous glands. They are differentiated epithelial cells that progressively accumulate lipids and release their contents through cellular degradation and cell membrane rupture, a process known as holocrine secretion. During differentiation, sebocytes accumulate large amounts of lipids in cytoplasmic vesicles in the form of lipid droplets. Sebocyte differentiation is modulated by several signaling pathways, such as the PPAR-g-dependent pathway or the COX pathway.

[0135] Method :

[0136] In this study, a sebocyte model derived from induced pluripotent stem cells from two different donors is used. These cells are treated with arachidonic acid to specifically induce lipogenesis. The modulatory activity of different plant extracts is therefore evaluated on lipogenesis in sebocytes. The lipid extract from apple seed oil is prepared according to Example 1.

[0137] The lipid extract from soybean oil is prepared according to Example 2.

[0138] The lipid extract from hazelnut oil is prepared according to Example 3.

[0139] The lipid extract from the gametophytes of Saccharina latissima is prepared according to Example 4a.

[0140] All these extracts are solubilized in DMSO (dimethyl sulfoxide) and are tested at 2 different concentrations.

[0141] Sebocytes derived from induced pluripotent stem cells from 2 different donors are incubated for 3 days with a specific molecule (PhenoCULT® N PC PHENOCELL, Grasse, France) to accelerate their maturation before testing. Sebocyte lipogenesis is induced by arachidonic acid (10 pM) for 48 hours in the presence or absence of the lipid extracts to be tested.

[0142] The results are generated from 3 independent experiments, but done with replicates, to obtain n > 4.

[0143] Quantification of lipid synthesis is assessed after Bodipy staining with high-resolution imaging and normalized with Hoechst staining (nuclei labeling).

[0144] Inter-group comparison is performed by one-way ANOVA followed by Tukey's test.

[0145] Results :

[0146] The addition of arachidonic acid (AA) leads to a significant accumulation of total lipids in human sebocytes after 48 hours. These results are summarized in Table 1 below.

[0147] [Table 1]

[0148] AA: arachidonic acid; sem: standard error of the mean

[0149] The compound cannabidiol, a reference product in the inhibition of lipogenesis, acts by activating TRPV4 ionic receptors (Olah et al., 2014). It is tested at 1 pM (also dissolved in DMSO); it significantly inhibits lipid accumulation. This result was expected, it validates the test (Table 1). Lipid extract of apple seed oil

[0150] The results obtained with the lipid extract of apple seed oil are presented in Table 2.

[0151] [Table 2]:

[0152] AA: arachidonic acid; sem: standard error of the mean

[0153] The lipid extract of apple seed oil, enriched with oxylipins, at both concentrations tested, significantly decreased (P<0.001 versus the arachidonic acid group) total lipids (Table 2). Indeed, the fold change allows us to assess the variations between different groups, a negative value indicating inhibition and a value lower than -2 indicating a reduction of more than 50%.

[0154] The inventors clearly demonstrate that a lipid extract of apple seed oil, enriched in oxylipins, in particular the main octadecanoids (10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE) induces a significant and very important inhibition of lipogenesis induced by arachidonic acid in human sebocytes, at the two concentrations tested.

[0155] Lipid extract of soybean seed oil

[0156] The results obtained with the lipid extract of soybean seed oil are presented in Table 3.

[0157] [Table 3]

[0158] AA: arachidonic acid; sm: standard error of the mean The lipid extract of soybean oil, enriched in oxylipins, at the two concentrations tested, significantly decreased (p<0.01 for the two concentrations tested) total lipids (Table 3). Indeed, the change factor allows us to highlight a reduction well above 50% of total lipids.

[0159] The inventors clearly demonstrate that a lipid extract of soybean seed oil, enriched in oxylipins, in particular the main octadecanoids (10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE) induces a significant and important inhibition of arachidonic acid-induced lipogenesis in human sebocytes, at both concentrations tested.

[0160] Lipid extract of hazelnut oil

[0161] The results obtained with the lipid extract of hazelnut oil are presented in Table 4.

[0162] [Table 4]

[0163] AA: arachidonic acid; sem: standard error of the mean

[0164] The lipid extract of hazelnut oil, enriched with oxylipins, at both concentrations tested, significantly decreased (P<0.001 versus the arachidonic acid group) total lipids (Table 4). Indeed, the change factor reached -3.8 at the lowest concentration tested, revealing a reduction of more than 3 times in total lipids.

[0165] The inventors clearly demonstrate that a hazelnut oil extract, enriched in oxylipins, in particular the main octadecanoids (10-TriHOME, 13-HODE, 9-HODE, 12,13-DiHOME) induces a significant and important inhibition of lipogenesis induced by arachidonic acid in human sebocytes, at the two concentrations tested.

[0166] Saccharina latissima extract

[0167] The results obtained with Saccharina latissima extract are presented in Table 5. [Table 5]

[0168] AA: arachidonic acid; sem: standard error of the mean

[0169] Saccharina latissima extract, enriched in oxylipins, at both concentrations tested, significantly decreased (P<0.001 versus the arachidonic acid group) total lipids (Table 5). Indeed, the change factor showed a reduction in total lipids of more than 3 times at 3 pg / mL of Saccharina latissima extract and a reduction in total lipids of more than 12 times at the concentration of 10 pg / mL of Saccharina latissima extract.

[0170] The inventors clearly demonstrate that an extract of Saccharina latissima, enriched in oxylipins, notably eicosanoids such as 15(S)-HEPE, induces a significant and important inhibition of lipogenesis induced by arachidonic acid in human sebocytes, at the two concentrations tested.

[0171] Consequently, all these results show that all these plant extracts enriched in oxylipins have the capacity to inhibit the accumulation of lipids in sebocytes, significantly reducing the production of sebum.

[0172] It is interesting to note that very different plant extracts are capable of exhibiting anti-seborrheic activity.

[0173] Example 6: Fractionation of a soybean oil extract obtained according to example 2 o Protocol 1: Fractionation Conditions

[0174] • The separation is carried out on a Chromabond™ Flash RS 80 SiOH 40-63 pm column (Macherey-Nagel™ brand), column volume of 145 mL, conditioning volume of 210 mL.

[0175] • The mobile phase is supplied using a pump with a flow rate of 5 mL / min.

[0176] • 14.6 g of soybean oil extract obtained according to example 2 are solubilized in 40 mL of heptane.

[0177] • The solution obtained is deposited at the top of the column by the pump at 5 mL / min. The column is then eluted with 400 mL of heptane.

[0178] The column is then eluted with 800 mL of a heptane - dichloromethane mixture (1:1) (v / v).

[0179] The column is then eluted with 500 mL of dichloromethane.

[0180] The column is then eluted with 500 mL of a dichloromethane - methanol mixture (1:1) (v / v).

[0181] The column is then eluted with 200 mL of methanol. o Protocol 2: UPLC-DAD analytical conditions

[0182] • Column: BEH Shield 1.7 pm C18 150*2.1 mm

[0183] • Mobile phase:

[0184] - A: water + 0.1% formic acid

[0185] - B: acetonitrile + 0.1% formic acid

[0186] • Gradient: according to Table 6 below

[0187] [Table 6]

[0188] • Column temperature: 50°C

[0189] • Flow rate: 0.4 mL / min

[0190] • Detection: 205 nm and 234 nm

[0191] • Injection volume: 1 pL o Protocol 3: CPG-MS analytical conditions

[0192] • Column: DB-5HT (Agilent Technologies); 30m x 0.32mm x 0.1pm

[0193] • Injection: 320°C; Mode = Split

[0194] • Oven: Temperature gradient (°C) according to Table 7 below

[0195] [Table 7] • Carrier gas flow rate: 1 mL / min

[0196] • Detection: MS Transferline Temperature = 350°C; Ion Source Temperature = 320°C; MS-EI; Full Scan Start Mass = 40; Full Scan End Mass = 800

[0197] • Injection volume: 1 pL o Results:

[0198] The fractions obtained are collected at the column outlet and analyzed by ultra-high pressure liquid chromatography coupled with a diode array detector (UPLC-DAD) as well as by gas chromatography coupled with a mass spectrometer (GC-MS). They are then combined according to their composition and then dried by evaporation under vacuum.

[0199] This fractionation allows obtaining 4 fractions with, in order of increasing polarity, triglycerides, diglycerides, and monoglycerides (Fraction 1 - 47% by mass), free fatty acids (Fraction 2 - 11% by mass), phytosterols (Fraction 3 - 9% by mass), then oxylipins (Fraction 4 - 8% by mass).

[0200] These different fractions were tested according to the method of example 5.

[0201] Table 8 below summarizes the results obtained with a lipid extract of soybean oil prepared according to Example 2 and the different fractions obtained according to Example 6 and tested at 5 pg / mL on the production of total lipids induced by arachidonic acid (AA) at 10 pM.

[0202] [Table 8]

[0203] : Corresponds to an extract enriched in oxylipins according to the invention

[0204] The strong sebum-regulating effect of soybean oil is found in this test.

[0205] Free fatty acid and sterol fractions show little or no inhibition of lipid induction by arachidonic acid-stimulated sebocytes.

[0206] Fraction 4 with oxylipins caused a much more marked decrease than unfractionated soybean oil extract in arachidonic acid-induced total lipid accumulation, clearly indicating that the oxylipin (oxidized fatty acid) fraction of soybean oil extract is capable of strongly inhibiting arachidonic acid-induced lipogenesis.

[0207] Bibliographic references FR2789085

[0208] Andreou et al., 2009, Lipids, 44: 207-215

[0209] Wheat, 2002, Trends in Plant Science Vol 7, No. 7, 315-321

[0210] Calder, 2012, J. Nutr. 142:592S-599S

[0211] 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

[0212] Liu et al., 2015, Brain Res. 0:220-246

[0213] Oenel et al., 2017, Plant Cell Physiol. 58(5): 925-933

[0214] Olah et al., 2014, J. Clin. Invest. 124(9), 3713-3724

[0215] Richardson et al., 2017, J. Agric. Food Chem., 65 : 1941-1951 Rustérucci et al., 1999, J Biol. Chem. Vol 274, N°51 : 36446-36455

[0216] Van Ginneken et al., 2011, Lipids in Health and Disease, 10, 104

Claims

Claims 1. Oxylipine for its use in the treatment of seborrhea.

2. Oxylipine for its use according to claim 1, characterized in that the seborrhea is that of the skin or the scalp.

3. Oxylipin for its use according to claim 1 or 2, characterized in that the oxylipin is chosen from octadecanoids, eicosanoids and their mixtures.

4. Oxylipin for its use according to any one of claims 1 to 3, characterized in that the oxylipin is chosen from 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-di hydroxy-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,11 E-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), acid 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,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 a mixture of these., 5. Oxylipin for its use according to claim 4, characterized in that the oxylipin is chosen from 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE, 12,13-DiHOME, 15-HEPE and their mixtures. Tl 6. Oxylipin for its use according to any one of claims 1 to 5, characterized in that the oxylipin is present in an oleaginous plant extract enriched in oxylipins.

7. Oxylipin for its use according to claim 6, characterized in that the oleaginous plant extract enriched with oxylipins is an extract of apple seeds, soybeans, hazelnuts, or gametophytes of brown algae such as Saccharina latissima enriched with oxylipins.

8. Oxylipin for its use according to claim 6 or 7, characterized in that the oleaginous plant extract enriched with oxylipins contains at least 25% by weight, for example at least 30% by weight, in particular at least 40% by weight, in particular at least 50% by weight, of oxylipins relative to the weight of dry extract.

9. Dermo-cosmetic or dermatological composition comprising at least one oxylipin with at least one dermo-cosmetically or dermatologically acceptable excipient, for its use in the treatment of seborrhea.

10. Composition for its use according to claim 9, characterized in that the seborrhea is that of the skin or the scalp.

11. Composition for its use according to claim 9 or 10, characterized in that the at least one oxylipin is chosen from octadecanoids, eicosanoids and their mixtures.

12. Composition for its use according to any one of claims 9 to 11, characterized in that the at least one oxylipin is chosen from 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11 E-octadecadienoic acid (13-HODE), 9-hydroperoxy-10E,12Z-octadecadienoic acid (9-HpODE), 13-hydroperoxy-9Z,11 E-octadecadienoic acid (13-HpODE), 9,10-di hydroxy-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,11 E-octadecadienoic acid (13-OxoODE), 9-hydroxy-10E,12Z,15Z-octadecatrienoic acid (9-HOTrE), 13-hydroxy-9Z,11 E,15Z-octadecatrienoic acid (13-HOTrE), 9-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid (9-HpOTrE), 11-hydroperoxy- 9Z,12Z,15Z-octadecatrienoic acid (11-HpOTrE), acid 12-hydroperoxy-9Z,13E,15E- octadecatrienoic acid (12-HpOTrE),13-hydroperoxy-9Z,11 E,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,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 a mixture thereof.

13. Composition for its use according to claim 12, characterized in that the at least one oxylipin is chosen from 10-TriHOME, 13-HODE, 9-HODE, 13- OxoODE, 9-OxoODE, 12,13-DiHOME, 15-HEPE and their mixtures.

14. Composition for its use according to any one of claims 9 to 13, characterized in that the at least one oxylipin is present in an oleaginous plant extract enriched in oxylipins.

15. Composition for its use according to claim 14, characterized in that the oleaginous plant extract enriched in oxylipins is an extract of apple seeds, soybeans, hazelnuts, or gametophytes of brown algae such as Saccharina latissima enriched in oxylipins.

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