Oxylipins in the treatment of seborrhea

Abstract

The present invention relates to oxylipids, the use thereof for the treatment of sebum overflow, more specifically present in an oleaginous plant extract, preferably rich in oxylipids. The invention also relates to a dermatocosmetic or dermatological composition comprising at least one oxylipidogen, preferably derived from oleaginous plants, and at least one dermatocosmetic or dermatological acceptable excipient, for the use thereof for the treatment of sebum overflow.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202480038863.X (22) Application Date 2024.04.26 (30) Priority Data FR2304484 2023.05.04 FR (85) PCT International Application Entering National Phase Date 2025.12.10 (86) PCT International Application Application Data PCT / EP2024 / 061632 2024.04.26 (87) PCT International Application Publication Data WO2024 / 227714 FR 2024.11.07 (71) Applicant: Pierre Fabre Skin Cosmetics Company, Address: Lavaux, France (72) Inventors: M. Letty, C. Dino, L. Garibaldi, C. Mias, N. Stewart (74) Patent Agency: Beijing Gecheng Intellectual Property Agency Co., Ltd., 11314 Patent Attorneys: Cheng Wei, Wu Shaotong (51) Int.Cl. A61K 8 / 365 (2006.01) A61K 8 / 92 (2006.01) A61P 17 / 08 (2006.01) A61P 17 / 10 (2006.01) A61Q 19 / 00 (2006.01) A61K 8 / 36 (2006.01) A61K 8 / 9706 (2006.01) (54) Invention Title: Oxylipin for Treating Seborrhea (57) Abstract: This invention relates to oxylipin for the treatment of seborrhea, more specifically in oily plant extracts preferably rich in oxylipin. The invention also relates to a skin cosmetic or dermatological composition comprising at least one oxylipin preferably derived from an oily plant, and at least one skin cosmetic or dermatologically acceptable excipient for the treatment of seborrhea. Claims 2 pages Description 17 pages Drawings 2 pages CN 121285365 A 2026.01.06 CN 1 21 28 53 65 A 1. Oxylipin for the treatment of seborrhea. 2. Oxylipin for the use according to claim 1, wherein the seborrhea is seborrhea of ​​the skin or scalp. 3. Oxylipin for the use according to claim 1 or 2, wherein the oxylipin is selected from octadecanoic acids, eicosanoic acids, and mixtures thereof. 4. The oxylipin for use according to any one of claims 1 to 3, characterized in that the oxylipin is selected from 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE), 9-peroxyhydroxy9-HpODE (9-10E,12Z-octadecadienoic acid), 13-peroxyhydroxy-9Z,11E-octadecadienoic acid (13-HpODE), 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-octadecadienoic acid (9-HOTrE), 13-hydroxy-9Z,11E,15Z-octadecadienoic acid (13-HOTrE), 9-peroxyhydroxy-10E,12Z,15Z- Octadectotrienoic acid (9-HpOTrE), 11-peroxyhydroxy-9Z,12Z,15Z-octadecatotrienoic acid (11-HpOTrE), 12-peroxyhydroxy-9Z,13E,15E-octadecatotrienoic acid (12-HpOTrE), 13-peroxyhydroxy-9Z,11E,15Z-octadecatotrienoic 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-peroxyhydroxy-5Z,8Z,11Z,13E,17Z-Eicosapentaenoic acid (15-HpEPE), 5-hydroxy-6E,8Z,11Z,14Z-Eicosatraenoic acid (5-HETE), 8-hydroxy-5Z,9E,11Z,14Z-Eicosatraenoic acid (8-HETE), 9-hydroxy-5Z,7E,11Z,14Z-Eicosatraenoic acid (9-HETE), 12-hydroxy-5Z,8Z,10E,14Z-Eicosatraenoic acid (12-HETE), 15-hydroxy-5Z,8Z,11Z,13E-Eicosatraenoic acid (15- HETE), 5-peroxyhydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HpETE), 11-peroxyhydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid (11-HpETE), 12-peroxyhydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HpETE), 15-peroxyhydroxy-5Z,8Z,11Z,13E-arachidonic acid (15-HpETE), and mixtures thereof.5. The oxaliplatin for the use according to claim 4, characterized in that the oxaliplatin is selected from 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE, 12,13-DiHOME, 15-HEPE, and mixtures thereof. 6. The oxaliplatin for the use according to any one of claims 1 to 5, characterized in that the oxaliplatin is present in an oily plant extract rich in oxaliplatin. 7. The oxaliplatin for the use according to claim 6, characterized in that the oily plant extract rich in oxaliplatin is an extract of the gametophytes of apple seeds, soybeans, hazelnuts, or brown algae such as Saccharina latissima, which are rich in oxaliplatin. 8. The oxaliplatin for the use according to claim 6 or 7, characterized in that, relative to the weight of the dried extract, the oily plant extract rich in oxaliplatin contains at least 25% by weight, for example at least 30% by weight, particularly at least 40% by weight, particularly at least 50% by weight of oxaliplatin. 9. A skin cosmetic or dermatological composition comprising at least one oxylipin and at least one skin cosmetic or dermatologically acceptable excipient for the treatment of seborrheic dermatitis. 10. The composition for the use according to claim 9, wherein the seborrheic dermatitis is seborrheic dermatitis of the skin or scalp. 11. The composition for the use according to claim 9 or 10, wherein the at least one oxylipin is selected from octadecanoic acids, eicosanoic acids, and mixtures thereof. Claims 1 / 2 page 2 CN 121285365 A 12. The composition for use according to any one of claims 9 to 11, characterized in that at least one oxylipin is selected from 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE), 9-peroxyhydroxy-10E,12Z-octadecadienoic acid (9-HpODE), 13-peroxyhydroxy-9Z,11E-octadecadienoic acid (13-HpODE), 9,10-dihydroxy-12Z-octadecadienoic 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-octadectrienoic acid (9-HOTrE), 13-hydroxy-9Z,11E,15Z-octadectrienoic acid (13-HOTrE), 9-peroxyhydroxy-10E,12Z,15Z-octadectrienoic acid (9-HpOTrE), 11-peroxyhydroxy-9Z,12Z ,15Z-Octadectrienoic acid (11-HpOTrE), 12-peroxyhydroxy-9Z ,13E ,15E-Octadectrienoic acid (12-HpOTrE), 13-peroxyhydroxy-9Z ,11E ,15Z-Octadectrienoic acid (13-HpOTrE), 12,13-epoxy-9Z-Octadectrienoic 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-peroxyhydroxy-5Z,8Z,11Z,13E, 17Z-Eicosapentaenoic acid (15-HpEPE), 5-hydroxy-6E,8Z,11Z, 14Z-Eicosatraenoic 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-Peroxyhydroxy-6E 13. The composition for use according to claim 12, characterized in that 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 for use according to any one of claims 9 to 13, characterized in that at least one oxylipin is present in an oily plant extract rich in oxylipins. 15. The composition for use according to claim 14, characterized in that the oxylipin-rich oily plant extract is an extract of the gametophytes of apple seeds, soybeans, hazelnuts, or brown algae such as kelp, which are rich in oxylipin. Claims 2 / 2 pages 3 CN 121285365 A Oxylipin Technology Field for Treating Seborrheic Acid

[0001] This invention relates to oxylipins, particularly plant extracts containing them, and cosmetics or skincare products containing them.Dermatological compositions for the regulation of sebum, particularly for the treatment of seborrhea and / or acne, preferably for the treatment of seborrhea. Background Art

[0002] Organisms consist of one or more cells, and the survival, defense, and proliferation functions of prokaryotes or eukaryotes depend on the metabolism of three major chemical families: carbohydrates, proteins, and lipids.

[0003] Lipids are natural substances; their functions are fundamental. They are major components of cellular structures, such as membrane phospholipids and glycolipids. They are also storage substances, serving as an energy source for the organism. They participate in cellular defense or signaling mechanisms and constitute coating elements such as waxes or keratin (Cuvelier et al., 2004).

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

[0005] Simple lipids, fatty acid esters, and alcohols (which can be glycerol (a component of triglycerides) or high molecular weight fatty alcohols (a component of ceramides)) can be distinguished from complex lipids such as phospholipids or glycolipids.

[0006] Fatty acids are the basic building blocks of lipids. They can have two additional sources in organisms: synthesis and diet.

[0007] Fatty acids are aliphatic monocarboxylic acids of variable length. The most common naturally occurring fatty acids have between 4 and 28 carbon atoms. Their carbon chain length and the number and type of their unsaturation are also variable. Saturated, monounsaturated (single double bond), and polyunsaturated (multiple double bonds) fatty acids are different. Unsaturated fatty acids can contain 1 to 6 double bonds in organisms. For the same chemical formula, there can be a large number of isomers, depending on the position of the double bonds and also on their cis or trans conformation.

[0008] In the plant kingdom, fatty acids can be oxidized to ketone forms (e.g., ricinoleic acid), hydroxylated forms (e.g., ricinoleic acid), or epoxidized forms (e.g., zirconia).

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

[0010] In the plant kingdom, triglycerides are usually stored as oily inclusions (oil bodies from the endoplasmic reticulum), which sometimes aggregate into large clusters in the cells of reserve tissues. This is especially true for seeds, which can make up more than 50% of their dry weight. Exceptionally, seeds can accumulate fatty acid esters and long-chain fatty alcohols (such as jojoba oil) instead of triglycerides. While this is less common, some fruits concentrate triglycerides in their pericarps (olives, avocados, laurel, etc.).

[0011] Essential omega-3 and omega-6 fatty acids for humans, such as arachidonic acid (C20: 4n-6), eicosapentaenoic acid (C20: 5n-3), and docosahexaenoic acid (C22: 6n-3), cannot be synthesized by the vertebrate enzyme library without a basic supply of linoleic acid and α-linolenic acid. Therefore, these nutrients are crucial and must be provided by food. These multi-...Saturated fatty acids are mainly found in food in the form of triglycerides, sterol esters, and phospholipids, whether esterified or in free form (Liu et al., 2015).

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

[0013] Major plant sources of α-linolenic acid include rapeseed oil, flaxseed oil, linseed oil, chia seed 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, specification 1 / 17 page 4 CN 121285365 A).

[0015] Polyunsaturated fatty acids are substrates for many enzymatic or non-enzymatic reactions that produce oxidative metabolites with various functions, called oxoliposides. Oxoliposides include oxidized polyunsaturated fatty acids and their derivatives. They are found in mammals, flowering plants (angiosperms), mosses, algae, bacteria, and fungi. Oxylipins include signaling molecules, ligands of transcription factors, or precursors for lipid mediator synthesis (Calder, 2012). For example, eicosanoates, including leukotrienes and prostaglandins, are a large family of oxidized derivatives of polyunsaturated fatty acids containing 20 carbon atoms. Dodecanoates are enzymatic oxidation products of polyunsaturated fatty acids with 22 carbon atoms, such as docosahexaenoic acid (DHA). Oxidation products of polyunsaturated fatty acids with 18 carbon atoms, such as linoleic acid or gamma-linolenic acid, belong to the octadecanoates. Octadecanates derived from linoleic acid include 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE). These two molecules have been described as biomarkers of oxidation in vivo (Lagarde, 2011). Peroxyhydroxy, epoxide, or ketone forms derived from linoleic acid have also been documented (Richardson et al., 2017). The most well-known oxidative metabolite of γ-linolenic acid is the metabolite that produces jasmonic acid, a cyclic derivative with excellent resistance activity against plant pathogens (Blée, 2002).

[0016] The oxidation of polyunsaturated fatty acids can occur in both non-enzymatic and enzymatic ways (Oenel et al., 2017). For the latter, the unsaturated position on the polyunsaturated fatty acid and the enzymatic environment will determine the type of oxylipoprotein formed. The main pathways are those of cyclooxygenase, lipoxygenase, and cytochrome P-450 (Andreou et al., 2009). While the enzymatic pathway appears to be the main route for the formation of oxidized 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 occur via a non-enzymatic pathway. This can occur in the oily plant matrix through the action of free radicals, the formation of which can be influenced by storage conditions (temperature, duration of exposure, etc.).(e.g., esterification) to promote the synthesis of oxidized fatty acids. These oxidized fatty acids can then be released after deesterification, particularly by the action of lipases (Oenel et al., 2017).

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

[0018] Sebaceous glands are exocrine glands present throughout the skin except for the palms and soles. They are more particularly present in the seborrheic areas of the face, especially the T-zone, which is the central area of ​​the face, back, and trunk that forms the T. It is usually associated with hair follicles. This is why we talk about pilosebaceous units. Sebaceous glands are responsible for the synthesis and secretion of sebum by sebaceous cells (the epithelial cells that make up sebaceous glands).

[0019] Sebum is a lipid complex synthesized under hormonal stimulation. It is an important component of the sebum film, which protects the skin from external aggressors and dehydration by playing a major barrier role. In association with this barrier function, sebum also has antibacterial properties thanks to oleic acid and palmitic acid, as well as providing antioxidant capacity through vitamin E. Therefore, sebum helps maintain the integrity of the skin barrier.

[0020] Seborrhea corresponds to the excessive secretion of sebum by the sebaceous glands. It can lead to aesthetic problems. The skin has a shiny appearance; the complexion is dull, and the pores of the pilosebaceous glands are dilated. In addition, cosmetics do not show good retention on this so-called oily skin. For scalp seborrhea, hair has an oily and dull appearance and is difficult to style. When seborrhea is severe, it is said to be oily and fluid and can be associated with a foul odor. Instruction manual 2 / 17 pages 5 CN 121285365 A

[0021] Acne is a chronic inflammatory skin disease of this pilosebaceous unit, resulting in the formation of retention lesions, namely open and / or closed comedones. It is important not to underestimate this condition and to treat it properly, as it can lead to disabling psychosocial consequences, especially due to scarring.

[0022] During acne, under the influence of various endogenous factors, mainly hormones, but also external factors such as pollution, poor diet, stress, etc., sebaceous gland dysfunction affects the quantity and quality of sebum. In fact, the skin of acne patients is characterized byIncreased sebum secretion, termed hyperspermia, and alterations in its overall composition, termed dyspermia, are observed. The lipid ratio present in sebum from subjects with acne differs from that from healthy skin, with significantly increased levels of free fatty acids, squalene and its oxides, and waxes.

[0023] This altered hyperspermia, i.e., more sebum and a thicker consistency, will contribute to the blockage of hair follicle ducts along with dyskeratosis. Furthermore, it will constitute a culture medium favorable for the development of pro-inflammatory acne bacteria, such as *Propionibacterium acnes*, which has been the most frequently described to date. Thus, all these factors will lead to the emergence of the first acne lesions, namely open and closed comedones, which may evolve into more severe inflammatory lesions, papules, pustules, and nodules.

[0024] Therefore, there is always a need to provide an effective solution to treat seborrhea, and thus also acne, and to address the aesthetic problems associated with seborrhea. Summary of the Invention

[0025] Therefore, the object of the present invention is to meet these needs. In fact, the inventors have surprisingly demonstrated that extracts rich in oxylipin derived from various plants have the ability to reduce sebum production. This anti-seborrheic activity is particularly advantageous in patients with acne-prone skin.

[0026] The present invention also relates to at least one oxylipin, more particularly to mixtures of oxylipins (e.g., plant extracts containing or rich in oxylipin), for the treatment of seborrheic and / or acne, preferably seborrheic.

[0027] The present invention also relates to the use of at least one oxylipin, more particularly to mixtures of oxylipins (e.g., plant extracts containing or rich in oxylipin) in the preparation of skin cosmetics or dermatological compositions for the treatment of seborrheic and / or acne, preferably seborrheic.

[0028] The present invention also relates to the use of at least one oxylipin, more particularly to mixtures of oxylipins (e.g., plant extracts containing or rich in oxylipin) for the treatment of seborrheic and / or acne, preferably seborrheic.

[0029] The present invention also relates to a method of treating seborrhea and / or acne, preferably seborrhea, comprising administering to a person in need an effective amount of at least one oxylipin, more particularly a mixture of oxylipins (e.g., plant extracts containing or rich in oxylipins).

[0030] The present invention also relates to a skin cosmetic or dermatological composition comprising at least one oxylipin, more particularly a mixture of oxylipins (e.g., plant extracts containing or rich in oxylipins) and at least one skin cosmetic or dermatologically acceptable excipient for the treatment of seborrhea and / or acne, preferably seborrhea.

[0031] The present invention also relates to the use of a skin cosmetic or dermatological composition in the preparation of a medicament for treating seborrhea and / or acne, preferably seborrhea, said skin cosmetic or dermatological composition comprising at least one oxylipin.More particularly, mixtures of oxylipins (e.g., plant extracts containing or rich in oxylipins) with at least one dermatologically or dermatologically acceptable excipient.

[0032] The present invention also relates to a method for treating seborrhea and / or acne, preferably seborrhea, comprising applying to a person in need an effective amount of a dermatological or dermatological composition comprising at least one oxylipin, more particularly, mixtures of oxylipins (e.g., plant extracts containing or rich in oxylipins) with at least one dermatologically or dermatologically acceptable excipient.

[0033] In the context of the present invention, oxylipins may preferably be mixtures of oxylipins. Oxylipins will more particularly be derived from plants, more particularly from oily plant materials, and may be present in plant extracts, more particularly in plant extracts rich in oxylipins. Plant extracts may more particularly be oily plant extracts, preferably rich in oxylipins.

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

[0035] In this invention, "extract" or "plant extract" means a product obtained after extracting a plant or a portion of a plant (e.g., a plant oil derived from a plant) with a solvent called an extraction solvent, and then, after partial or complete evaporation of the extraction solvent, the product may optionally be in a concentrated or dried form. In particular, it may be a dried extract. Extraction may also be accomplished by mechanical processes such as pressing.

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

[0037] In this invention, "oily plant material" means an oily plant or a portion of a plant, i.e., a plant rich in fats. Examples include oily seeds or fruits (e.g., apple seeds, soybeans, flax seeds, safflower seeds, cumin seeds, shepherd's purse seeds, canola seeds, perilla seeds, chia seeds, rapeseed, hazelnuts, or mixtures thereof), gametophytes (e.g., brown algae, particularly sugar kelp (Saccharina latissima)) or mixtures thereof. It may also include vegetable oils (e.g., apple seed oil, soybean oil, flaxseed oil, safflower oil, cumin oil, rice bran oil, shepherd's purse oil, canola oil, perilla oil, chia seed oil, rapeseed oil, hazelnut oil, or mixtures thereof).

[0038] In this invention, "oily plant extract" refers to an extract obtained from oily plant material as described above.

[0039] In this invention, "fatty acid" refers to a carboxylic acid R1CO2H, wherein the chain R1 is saturated or contains one or more, particularly...The carboxylic acid is a straight-chain or branched hydrocarbon chain with 1, 2, 3, 4, 5, or 6 C=C double bonds, and 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 this invention, "polyunsaturated fatty acid" refers to a fatty acid as described above, wherein the hydrocarbon chain contains one or more, particularly 1, 2, 3, 4, 5, or 6 C=C double bonds.

[0041] In this invention, "free fatty acid" refers to a fatty acid that does not combine with other molecules (e.g., with glycerol or its derivatives to produce glycerides or with alcohols to produce fatty esters).

[0042] In this invention, "oxylipin" refers to an oxidized molecule derived from the enzymatic or non-enzymatic oxidation of polyunsaturated fatty acids. The oxidation of polyunsaturated fatty acids can particularly introduce one or more, especially one, two, or three oxygen-containing groups, particularly selected from hydroxyl (OH), peroxyhydroxyl (-OOH), ketone (=O; oxygen is bonded to a carbon atom through a double bond), epoxy (-O-; oxygen is bonded to two adjacent carbon atoms) groups, preferably one, two, or three hydroxyl and / or ketone groups, particularly substituting one or more, especially one, two, or three C=C double bonds, thereby forming conjugation with another double bond and / or substituting the C=C unit with a C(GO1)-C(GO2) unit, wherein GO1 and GO2 each independently represent the oxidizing group as described above. Oxadiposylfatty acids can particularly be octadecanoic acids, eicosanoic acids, or mixtures thereof.

[0043] In this invention, “octadecanoic acid” refers to an oxidized molecule derived from the enzymatic or non-enzymatic oxidation of a polyunsaturated fatty acid containing 18 carbon atoms as described above. The polyunsaturated fatty acid containing 18 carbon atoms may be, for example, linoleic acid, α-linolenic acid, γ-linolenic acid or linolenic acid, preferably linoleic acid, α-linolenic acid or γ-linolenic acid. Examples include 9- (Instruction manual, page 4 / 17, 7 CN 121285365 A) hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE), 9-peroxyhydroxy-10E,12Z-octadecadienoic acid (9-HpODE), 13-peroxyhydroxy-9Z,11E-octadecadienoic acid (13-HpODE), 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-octadecadienoic acid9-HOTrE, 13-hydroxy-9Z,11E,15Z-octadecanetrienoic acid (13-HOTrE), 9-peroxyhydroxy-10E,12Z,15Z-octadecanetrienoic acid (9-HpOTrE), 11-peroxyhydroxy-9Z,12Z,15Z-octadecanetrienoic acid (11-HpOTrE), 12-peroxyhydroxy-9Z,13E,15E-octadecanetrienoic acid (12-HpOTrE), 13-peroxyhydroxy-9Z,11E,15Z-octadecanetrienoic acid (13-HpOTrE), 12,13-epoxy-9Z-octadecanetrienoic acid (12,13-EpOME), or mixtures thereof.

[0044] In this invention, "eicosanoic acid" refers to an oxidized molecule derived from the enzymatic or non-enzymatic oxidation of a polyunsaturated fatty acid containing 20 carbon atoms, as described above. The polyunsaturated fatty acid containing 20 carbon atoms can be, for example, arachidonic acid or eicosapentaenoic acid. Examples include leukotrienes and / or prostaglandins. 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-peroxyhydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid (15-HpEPE), 5-hydroxy-6E,8Z,11Z,14Z-eicosatraenoic acid (5-HETE), 8-hydroxy-5Z,9E,11Z,14Z-eicosatraenoic acid (8-HETE), and 9-hydroxy-5Z,7E,11Z,14Z-eicosatraenoic acid (9- HETE), 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE), 15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-HETE), 5-peroxyhydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HpETE), 11-peroxyhydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid (11-HpETE), 12-peroxyhydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HpETE), 15-peroxyhydroxy-5Z,8Z,11Z,13E-arachidonic acid (15-HpETE), or mixtures thereof.

[0045] In this invention, "extract rich in oxaliponins" refers to the extract described above obtained from a plant or part thereof containing oxaliponins (whose oxaliponin synthesis is stimulated), or the extract described above that has undergone an oxaliponin enrichment step (e.g., by chromatography).

[0046] In this invention, "nonpolar solvent" refers to a lipophilic solvent capable of dissolving low-polarity compounds (i.e., LogP greater than or equal to 1), selected, for example, heptane, hexane, limonene, chloroform, dichloromethane, supercritical CO2, supercritical CO2 / ethanol mixtures, and mixtures of these solvents. Examples also include lipophilic solvents of 100% biological origin, such as EcoXtract® LIPOCOS (supplier Pennakem Europa).

[0047] In this invention, "hydrophilic solvent" refers to a polar solvent selected, for example, water, subcritical water, water-miscible alcohols such as C1-C3 alcohols, C3-C5 diols, glycerol, acetone, and mixtures thereof.

[0048] In this invention, "organic solvent immiscible with vegetable oils" refers to an organic solvent that cannot be mixed with or can only be partially mixed with vegetable oils, such that the mixture of the organic solvent and the vegetable oil produces a heterogeneous mixture in which at least two distinct phases can be observed.

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

[0050] In this invention, "C3-C5 diol" refers to a saturated straight-chain or branched hydrocarbon chain containing 3 to 5 carbon atoms, said chain having two OH functional groups. For example, propylene glycol may be mentioned.

[0051] In this invention, the term "ambient temperature" refers to a temperature between 15°C and 40°C, preferably between 20°C and 30°C, particularly about 25°C. Specification 5 / 17 pages 8 CN 121285365 A

[0052] Detailed Description of the Invention This invention relates to an oxylipin, comprising a mixture of oxylipins, which may be in the form of a plant extract containing or rich in oxylipins, for the treatment of seborrhea and / or acne, preferably for the use of seborrhea. Seborrhea may be seborrhea of ​​the skin or scalp.

[0053] Oxylipins are as described above, and may be particularly selected from octadecanoic acids, eicosanoic acids, and mixtures thereof. Therefore, oxylipoproteins can be selected from 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE), 9-peroxyhydroxy-10E,12Z-octadecadienoic acid (9-HpODE), 13-peroxyhydroxy-9Z,11E-octadecadienoic acid (13-HpODE), 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-Oxadecadienoic acid (9-OxoODE), 13-Keto-9Z,11E-Oxadecadienoic acid (13-OxoODE), 9-Hydroxy-10E,12Z,15Z-Oxadecatrienoic acid (9-HOTrE), 13-Hydroxy-9Z,11E,15Z-Oxadecatrienoic acid (13-HOTrE), 9-Peroxyhydroxy-10E,12Z,15Z-Oxadecatrienoic acid (9-HpOTrE), 11-Peroxyhydroxy-9Z,12Z,15Z-Oxadecatrienoic acid (11-HpOTrE), 12-Peroxyhydroxy-9Z,13E,15E-Oxadecatrienoic acid (12-HpOTrE), 13-Peroxyhydroxy- 9Z,11E,15Z-Octadectrienoic acid (13-HpOTrE), 12,13-Epoxy-9Z-Octadectrienoic 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-Peroxyhydroxy-5Z,8Z,11Z,13E,17Z-Eicosapentaenoic acid (15-HpEPE), 5-Hydroxy-6E,8Z,11Z,14Z-Eicosatraenoic 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-peroxyhydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HpETE), 11- Peroxyhydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid (11-HpETE), 12-peroxyhydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HpETE), 15-peroxyhydroxy-5Z,8Z,11Z,13E-arachidonic acid (15-HpETE), and mixtures thereof.

[0054] According to a specific 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] The oxylipin is preferably present in plant extracts, and more preferably in plant extracts rich in oxylipins. PlantsThe extract contains at least one oxaliponin as described above, particularly at least one oxaliponin selected from 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE, 12,13-diHOME, 15-HEPE, and mixtures thereof. The plant extract may be more particularly an oily plant extract, preferably rich in oxaliponins, which can be obtained from various oily plant materials.

[0056] Oily plant materials are oily plants or parts of plants, i.e., rich in fats, more specifically rich in plant oils containing polyunsaturated fatty acids. Thus, oily plant materials can be, for example, plant oils containing polyunsaturated fatty acids. Oily plant materials can also be gametophytes, preferably containing polyunsaturated fatty acids.

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

[0058] Vegetable oils containing polyunsaturated fatty acids may be, for example, apple seed oil, soybean oil, flaxseed oil, safflower oil, cumin oil, rice bran oil, flaxseed oil, rapeseed oil, perilla oil, chia seed oil, rapeseed oil, hazelnut oil, or mixtures thereof. Gametophyte specification 6 / 17 pages 9 CN 121285365 A can be the gametophyte of brown algae (e.g., sugar kelp).

[0059] Oily plant extracts, preferably oily plant extracts rich in oxaliplatin, will more particularly be apple seed extract (more particularly apple seed oil), soybean extract (more particularly soybean oil), hazelnut extract (more particularly hazelnut oil) or extracts of gametophytes of brown algae (e.g., sugar kelp), so that the extract contains oxaliplatin, and is preferably rich in oxaliplatin.

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

[0061] According to a specific embodiment of the invention, prior to extraction of the plant or its parts, the synthesis of oxaliplatin can be stimulated in the plant or its parts (e.g., plant oil or gametophyte). This means altering the growth or culture parameters of the plant or its parts in a manner that stimulates the synthesis of oxaliplatin in the plant or its parts and thus increases the oxaliplatin content in the plant or its parts.

[0062] Oxyliptin synthesis can be stimulated in plants or their parts, for example, by optimizing parameters favorable to the oxidation process, such as temperature, or by enzymatic treatment.

[0063] Oxyliptin synthesis can also be stimulated by induction, more particularly in the context of plant cell culture, such as gametophytes.

[0064] According to another embodiment, plant extracts can be enriched with oxyliptin, for example by molecular distillation of the extract and / or by fractionation of the extract, particularly by chromatographic techniques. Oxyliptin synthesis can be stimulated in the plant or its parts as described above prior to extraction of the plant or its parts.

[0065] When the plant or its parts are vegetable oils containing polyunsaturated fatty acids (hereinafter referred to as “vegetable oils”), vegetable oils can be obtained by pressing oily plant raw materials (e.g., grains, seeds, etc.), particularly by cold pressing, i.e., without heating, at ambient temperature, preferably followed by a filtration step.

[0066] Vegetable oils can also be obtained by extracting whole or ground oily plant raw materials (e.g., grains, seeds, etc.) with a nonpolar solvent. This extraction can be carried out with supercritical CO2, with or without ethanol as a co-solvent, and optionally followed by a filtration step.

[0067] Vegetable oils can also be obtained by extracting oily plant materials with a hydrophilic solvent in the presence of at least one enzyme (e.g., pectinase), particularly a mixture of enzymes such as pectinase.

[0068] Preferably, the vegetable oil will be obtained by pressing the oily plant material, particularly by cold pressing, i.e., without heating, at ambient temperature, preferably followed by a filtration step.

[0069] Oily plant extracts can be obtained from vegetable oils by extraction with a hydrophilic aqueous solution, subcritical water, or an organic solvent immiscible with the vegetable oil (optionally mixed with water). Oily plant extracts can be enriched with oxylipin, for example by molecular distillation of the extract, or by technical fractionation of the extract.

[0070] Organic solvents immiscible with vegetable oils can be used as mixtures with water, particularly with a volume ratio of organic solvent / water between 80 / 20 and 100 / 0, particularly between 85 / 15 and 95 / 5, particularly about 90 / 10.

[0071] Organic solvents immiscible with vegetable oils may in particular be C1 to C3 alcohols, optionally mixed with water, particularly at the above-mentioned organic solvent / water volume ratio. C1 to C3 alcohols are more particularly methanol, ethanol, n-propanol, or isopropanol, especially methanol, ethanol, or isopropanol, preferably ethanol.

[0072] The extraction solvent may in particular 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 with a volume ratio of about 90 / 10, or an isopropanol / water mixture with a volume ratio of about 90 / 10.

[0073] According to a preferred embodiment, oily plant extracts can be obtained by the method described below according to the invention.

[0074] The method for preparing oily plant extracts includes the step of extracting vegetable oils with an extraction solvent, said extraction solvent containing...The extraction solvent comprises, in particular, an aqueous solution of hydrophilic water, subcritical water, or an organic solvent immiscible with vegetable oil, optionally mixed with water.

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

[0076] The organic solvent immiscible with vegetable oil can be, in particular, a C1 to C3 alcohol.

[0077] The extraction solvent can be, in particular, a C1 to C3 alcohol optionally mixed with water.

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

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

[0080] The extraction solvent may be selected in particular from methanol, methanol / water mixtures, ethanol, ethanol / water mixtures, isopropanol, and isopropanol / water mixtures.

[0081] According to a preferred embodiment, the extraction solvent is methanol, an ethanol / water mixture with a volume ratio of about 90 / 10, or an isopropanol / water mixture with a volume ratio of about 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 h, and especially at a temperature between 15°C and 25°C, particularly about 20°C. The amount of extraction solvent used for this extraction is advantageously 0.5 to 3 g per 1 g of vegetable oil, particularly 1 to 3 g.

[0083] The extract phase and the lipid phase are then obtained at the end of the extraction. The extract phase is advantageously separated from and recovered from the lipid phase, and then partially or completely dried, especially under vacuum, to remove more or less of the extraction solvent, and if the solvent is completely removed, a dried extract is obtained, or a concentrated extract diluted in the residual solvent is obtained.

[0084] According to one embodiment of the invention, the method according to the invention comprises the following two consecutive steps: 1. obtaining a vegetable oil, and 2. extracting the vegetable oil with an extraction solvent, said extraction solvent comprising, in particular, a hydrophilic aqueous solution, subcritical water, or an organic solvent immiscible with the vegetable oil, optionally mixed with water.

[0085] According to a preferred embodiment of the invention, the method according to the invention comprises the following consecutive steps: 1. optionally obtaining a vegetable oil, 2. extracting the vegetable oil with an extraction solvent to obtain an extract phase and a lipid phase, said extraction solvent comprising, in particular, a hydrophilic aqueous solution, subcritical water, or an organic solvent immiscible with the oil from the achene fruit of the plant, optionally mixed with water, 3. recovering the extract phase obtained in step (2), and 4. partially or completely drying the extract phase to obtain a concentrated or dried extract according to the invention.

[0086] Step (1) can be carried out by pressing oily plant material (e.g., grains, seeds, etc.), especially by cold pressing, i.e. without heating, at ambient temperature, preferably followed by a filtration step.

[0087] Step (2) will advantageously be carried out using the extraction solvent as described above.

[0088] The extraction solvent can be methanol, ethanol or isopropanol, optionally mixed with water, especially with an organic solvent / water volume ratio between 80 / 20 and 100 / 0, especially between 85 / 15 and 95 / 5, especially about 90 / 10. An advantageous extraction solvent is an ethanol / water mixture with a volume ratio of about 90 / 10. Specification 8 / 17 pages 11 CN 121285365 A

[0089] The extraction step (2) can be carried out by mixing the vegetable oil with the extraction solvent for 1 to 12 h, and especially at a temperature of 15°C to 25°C, especially about 20°C. The amount of extraction solvent used for this extraction is advantageously 0.5 to 3 g per 1 g of vegetable oil, especially 1 to 3 g. The extraction step (2) enables the final extraction phase and lipid phase of interest to be obtained.

[0090] Step (3) is advantageously performed by separating the extraction phase from the lipid phase.

[0091] Step (4) is advantageously performed under vacuum.

[0092] The oxylipin-rich extract will particularly 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 oxylipin relative to the weight of the dried extract. The oxylipin-rich extract may contain up to 100% by weight of oxylipin.

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

[0094] Oxyliptins are more particularly derived from plants, more particularly from oily plant materials, and can be present in plant extracts as described above, and more particularly in plant extracts rich in oxyliptins. Plant extracts can be more particularly oily plant extracts as described above, preferably rich in oxyliptins. Oily plant extracts are more particularly apple seed extract (more particularly apple seed oil), soybean extract (more particularly soybean oil), hazelnut extract (more particularly hazelnut oil), or extracts of gametophytes from brown algae (e.g., kelp), which therefore contain oxyliptins.

[0095] The skin cosmetics or dermatological compositions according to the invention are generally in a form suitable for topical application. Therefore, the skin cosmetics or dermatological compositions according to the invention are not intended to be rinsed off after application (generally, after applying the composition).(Do not rinse or wash the skin for at least 12 hours). Therefore, skin cosmetics or dermatological compositions can be provided in forms commonly known for topical application, i.e., in particular, lotions, emulsions, serums, balms, masks, creams, dispersions, gels, foams, sprays, and shampoos.

[0096] Skin cosmetics or dermatological compositions may also contain surfactants, complexing agents, preservatives, antioxidants such as tocopherols, stabilizers, emulsifiers, thickeners, gelling agents, moisturizers, emollients, trace elements, essential oils, fragrances, dyes, matting agents, chemical or mineral sunscreens, humectants, thermal spring water, etc.

[0097] The following examples and accompanying drawings illustrate the invention, but do not limit its scope. Brief Description of the Drawings

[0098] [Figure 1]: High performance liquid chromatography (HPLC) chromatogram (UV 236 nm) of lipid extracts of gametophytes from Laminaria japonica, showing the presence of molecules with UV characteristics of oxylipin (in particular 12(S)-HEPE and 15(S)-HEPE). Oxyliptin 15(S)HEPE was the most abundant.

[0099] [Figure 2]: Oxyliptin production of gametophytes of *Laminaria japonica* suspended in culture medium for 48 h without the addition of phosphate (75 mg / L K2HPO4 + 50 mg / L β-glycerophosphate Na2×H2O) and / or iron Fe3+ (0.91 mg / L FeCl3·6H2O) or added to the culture medium. Oxyliptin content is expressed as mg equivalent of 15(S)HEPE per liter of suspension.

[0100] [Figure 3]: Changes in the amount of oxyliptin produced per liter of culture medium (in mg equivalent of 15(S)HEPE) over time for culture A (control) and culture B (phosphate-rich medium).

[0101] [Figure 4]: Changes in the amount of oxylipin produced per liter of culture medium (in mg equivalent of 15(S)HEPE) over time for culture A (control) and culture B (induced by phosphate and iron). On day 34 of culture, induction was performed 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 (indicated by arrows on page 9 / 17 of the instruction manual, CN 121285365 A). Detailed Embodiments

[0102] Example Example 1: Obtaining a lipid extract from apple seed oil The lipid extract was obtained as follows: • Apple seeds (Pyrus malus L.) were cold-pressed to obtain apple seed oil, the fatty acid fraction of which showed a linoleic acid content of 50% by weight; • Apple seed oil was extracted with an ethanol / water mixture (90 / 10 v / v) at 2 g of 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 obtain the lipid extract.

[0103] The lipid extract was obtained with an extraction yield of approximately 1%, wherein the main octadecanoic acids were 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, and 9-OxoODE.

[0104] Example 2: Obtaining a lipid extract from soybean oil The lipid extract was obtained as follows: • Cold-pressed soybeans (Glycine max (L.) Merr.) were used to obtain soybean oil, the fatty acid fraction of which showed a content of 55% linoleic acid and 8% α-linolenic acid; • Soybean oil was extracted with an ethanol / water mixture (90 / 10 v / v) at 2 g of 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 obtain the lipid extract.

[0105] The lipid extract was obtained with an extraction yield of approximately 5.5%, wherein the main octadecanoic acids were 10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, and 9-OxoODE.

[0106] Example 3: Obtaining a lipid extract from hazelnut oil. The lipid extract was obtained as follows: • Hazelnut oil was obtained by cold pressing of shelled hazelnuts (Corylus avellana L.), the fatty acid fraction of which showed a linoleic acid content of 15%; • Hazelnut oil was extracted with an ethanol / water mixture (90 / 10 v / v) at 2 g of 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 obtain the lipid extract.

[0107] The lipid extract was obtained with an extraction yield of about 1.5%, the main octadecanoic acids being 10-TriHOME, 13-HODE, 9-HODE and 12,13-DiHOME.

[0108] Example 4: Obtaining a lipid extract from kelp 4a: Experiments in media with or without the addition of phosphate and / or ferric iron. The male gametophytes of a kelp plant were cultured in reconstituted seawater. Biomass culture was carried out in a bioreactor at 18°C, with CO2-rich air supplied to maintain the pH at 8.0 and the suspension pneumatically stirred. The culture was irradiated with LEDs during a 16 / 8 h photoperiod. Once the biomass reached critical density, the gametophyte biomass was collected on a nylon sieve and vacuum lyophilized before solid / liquid extraction. This was accomplished by milling in the presence of a solvent (e.g., a 52:48 mixture of ethanol and methyl ethyl ketone (v / v)). Milling was performed using a vibrator (Retsch MM 400) or alternatively, an ultrasonic mill (Branson, Digital Sonifier 450). Between milling operations, the tubes containing biomass were centrifuged at 8000 g for 10 min. The clear supernatant was collected, and fresh solvent was then introduced into the milling tubes containing the biomass particles for a second milling operation.The grinding steps were repeated. The collected supernatant fraction underwent a decolorization step. For this purpose, the fraction was diluted in purified water and incubated in the dark at 4°C. The tubes were then centrifuged and the decolorized supernatant was collected. The solvent carrier (DMSO, pentylene glycol, Eutanol® G, etc.) was then placed in the decolorized fraction to ensure the final dry matter content after complete evaporation of the solvent and water, leaving only the dry matter dissolved in the selected carrier.

[0109] Analysis was performed by HPLC (Alliance WATERS 2695 system, controlled by Empower Ver 2.03 software equipped with WATERS 2996 diode array detector), using a CORTECS C8 2.7 μ 4.6 × 150 mm column equipped with a CORTECS C8 2.7 μ 3.9 × 5 mm VG guard column, which was inserted into a column oven at 35°C. The mobile phase consisted of: A = distilled water containing 0.1% formic acid; B = acetonitrile containing 0.1% formic acid; and C = methanol containing 0.1% formic acid. The flow rate was 0.7 mL / min, with the following gradients: 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; and 35 min 50% A, 50% B. UV detection was performed at 236.5 nm. The device was calibrated by continuous injection of 10 mg / L 15(S)-HEPE (Cayman Chemical) solution, and the linear correlation between the detection area and the analyte is presented.

[0110] The chromatogram showed the presence of several isomers and derived oxylipins, which had the same UV characteristics as 15(S)-HEPE (Figure 1). These formed peaks in the retention time range of 10 to 30 minutes, with the most abundant peak, 15(S)-HEPE, having a retention time of 13 minutes. The oxylipin content was expressed as 15(S)-HEPE equivalent (μg) by summing the peak areas of 15(S)-HEPE and the isomers and derived oxylipins.

[0111] After adding phosphate (75 mg / L K2HPO4 + 50 mg / L β-glycerophosphate Na2xH2O) and / or iron Fe3+ (0.91 mg / L FeCl3.6H2O) to the culture medium, analysis of samples from control and induced biomass revealed that the total oxylipin yield per liter of suspension from the control culture was 0.23 mg / L, while the total oxylipin yield from cultures induced using phosphate or ferric iron (Fe3+) was similar, approximately 0.46 mg / L. The simultaneous addition of phosphate and ferric iron...The total oxygen-lipid production per liter of suspension was observed to be 0.58 mg / L (Figure 2).

[0112] 4b: Male gametophytes of *Laminaria japonica* were cultured for 63 days in a 10-L bioreactor by adding phosphate to the bioreactor at the start of cultivation. 5 L of this culture was transferred to another bioreactor to produce two parallel cultures, A and B. Both cultures A and B received 5 L of pre-sterilized and cooled fresh culture medium. Phosphate was added further only to culture B. Thus, the phosphate concentration of culture A was 37.5 mg / L K2HPO4 and 25 mg / L β-glycerophosphate Na2 x H2O provided by the culture medium, and the phosphate concentration of culture B was 112.5 mg / L K2HPO4 and 75 mg / L β-glycerophosphate Na2 x H2O provided by the culture medium and further added. Both cultures were then cultured identically under the same light, temperature, and pH control conditions. Biomass was collected and then periodically frozen at -20°C. HPLC analysis of total oxylipin, expressed as 15(S)-HEPE equivalents (mg / L culture medium), showed that from day 10 of culture, the culture receiving the most phosphate (B) had a higher content than the control culture (A); this difference peaked on day 15 of culture (Figure 3).

[0113] 4c: Experiment on inducing culture by adding phosphate and iron to the bioreactor during culture Male gametophytes of *Laminaria japonica* were cultured in a 10-L bioreactor for 63 days. 5 L of this culture was transferred to another bioreactor to produce two parallel cultures, A and B. Both cultures A and B received 5 L of pre-sterilized and cooled fresh culture medium. Both cultures were then cultured identically for 34 days under the same light, temperature, and pH control conditions. On day 34, phosphate and ferric iron were added only to culture B (induced culture) by adding 75 mg / L K2HPO4, 50 mg / L β-glycerophosphate Na2xH2O and 1 mg / L FeCl3.6H2O. Biomass was collected and then frozen periodically at -20°C. HPLC analysis of total oxylipin, expressed as 15(S)-HEPE equivalent (mg / L culture medium), showed that from day 36, i.e., 48 hours after induction, the content of the induced culture (B) was greater than that of the control culture (A); this difference was observable until the end of the experiment (Figure 4).

[0114] Example 5: Effect of different plant extracts containing oxylipin on arachidonic acid-induced adipogenesis in sebaceous cells. Sebaceous cells are the main cell type of sebaceous glands. They are differentiated epithelial cells that undergo cell degradation and cell turnover.The cell membrane ruptures, gradually accumulating lipids and releasing its contents; this process is called holoplasty. During differentiation, sebaceous cells accumulate large amounts of lipids in the form of lipid droplets in cytoplasmic vesicles. Sebaceous cell differentiation is regulated by multiple signaling pathways, such as the PPAR-g-dependent pathway or the COX pathway.

[0115] Methods: In this study, sebaceous cell models derived from induced pluripotent stem cells from two different donors were used. These cells were treated with arachidonic acid to specifically induce adipogenesis. Therefore, the regulatory activity of different plant extracts on adipogenesis in sebaceous cells was evaluated.

[0116] A lipid extract derived from apple seed oil was prepared according to Example 1.

[0117] A lipid extract derived from soybean oil was prepared according to Example 2.

[0118] A lipid extract derived from hazelnut oil was prepared according to Example 3.

[0119] A lipid extract derived from gametophytes of kelp was prepared according to Example 4a.

[0120] All these extracts were dissolved in DMSO (dimethyl sulfoxide) and tested at two different concentrations.

[0121] Sebaceous cells derived from induced pluripotent stem cells from two different donors were incubated with a specific molecule (PhenoCULT® NPC PHENOCELL, Grasse, France) for 3 days to accelerate their maturation prior to testing. Adipogenesis in sebaceous cells was induced for 48 hours with arachidonic acid (10 μM) in or without the lipid extract to be tested.

[0122] Results were generated from three independent experiments, but repeated to obtain n>4.

[0123] Quantification of lipid synthesis was assessed using high-resolution imaging after Bodipy staining and normalized by Hoechst staining (nuclear markers).

[0124] Intergroup comparisons were performed using one-way ANOVA and Tukey's test.

[0125] Results: 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.

[0126] [Table 1] AA: Arachidonic acid; esm: Standard error of mean. Cannabidiol compounds are reference products for inhibiting lipogenesis, acting by activating TRPV4 ion channels (Olah et al., 2014). Tested at 1 µM (also soluble in DMSO); it significantly inhibited lipid accumulation. This result was expected; it validates the test (Table 1).

[0127] Lipid extract of apple seed oil. Results obtained with the lipid extract of apple seed oil are presented in Table 2. Specification 12 / 17 pages 15 CN 121285365 A

[0128] [Table 2]: AA: Arachidonic acid; esm: Standard error of mean. The lipid extract of apple seed oil rich in oxylipin was significantly reduced at both test concentrations (p < 0.05 relative to the arachidonic acid group).0.001) Total lipids (Table 2). In fact, fold changes can be understood to account for changes between different groups, with negative values ​​indicating inhibition and values ​​less than -2 indicating a reduction of more than 50%.

[0129] The inventors have clearly demonstrated that, at both test concentrations, the lipid extract of apple seed oil rich in oxylipin, particularly the major octadecanoic acids (10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE), has a significant and very important inhibitory effect on arachidonic acid-induced adipogenesis in human sebaceous cells.

[0130] Lipid extract of soybean oil The results obtained with the lipid extract of soybean oil are shown in Table 3.

[0131] [Table 3] AA: arachidonic acid; esm: standard error of the mean The lipid extract of soybean oil rich in oxylipin significantly reduced (p < 0.01 for both test concentrations) total lipids (Table 3). In fact, fold changes can be demonstrated to indicate a reduction of more than 50% in total lipids.

[0132] The inventors have clearly demonstrated that, at both test concentrations, the lipid extract of soybean oil rich in oxylipin, particularly the major octadecanoic acids (10-TriHOME, 13-HODE, 9-HODE, 13-OxoODE, 9-OxoODE), significantly and very importantly inhibited arachidonic acid-induced adipogenesis in human sebaceous cells.

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

[0134] [Table 4] Specification 13 / 17 pages 16 CN 121285365 A AA: arachidonic acid; esm: standard error of the mean The lipid extract of hazelnut oil rich in oxylipin significantly reduced (p < 0.001 relative to the arachidonic acid group) total lipids at both test concentrations (Table 4). In fact, at the lowest concentration tested, the fold change reached -3.8, revealing a reduction of more than 3-fold in total lipids.

[0135] The inventors have clearly demonstrated that, at both test concentrations, the extract of hazelnut oil rich in oxylipin, particularly the major octadecanoic acids (10-TriHOME, 13-HODE, 9-HODE, 12,13-DiHOME), significantly and very importantly inhibited arachidonic acid-induced adipogenesis in human sebaceous cells.

[0136] The results obtained with the extract of kelp sugar are listed in Table 5.

[0137] [Table 5] AA: arachidonic acid; esm: standard error of the mean. The extract of kelp sugar rich in oxylipin significantly reduced (p < 0.001 relative to the arachidonic acid group) total lipids at both test concentrations (Table 5). In fact, the fold change demonstrated a reduction of more than 3-fold in total lipids at 3 μg / mL of the kelp sugar extract, and at 10 μg / mL...At a concentration of μg / mL, the total lipids of the extract from *Kelpium saccharifolium* were reduced by more than 12-fold.

[0138] The inventors have clearly demonstrated that, at both test concentrations, the extract from *Kelpium saccharifolium*, rich in oxylipin, particularly eicosanoic acid (e.g., 15(S)-HEPE), has a significant and substantial inhibitory effect on arachidonic acid-induced lipogenesis in human sebaceous cells.

[0139] Therefore, all these results indicate that all these oxylipin-rich plant extracts have the ability to inhibit lipid accumulation in sebaceous cells and significantly reduce sebum production.

[0140] Interestingly, very different plant extracts were able to exhibit anti-seborrheic activity.

[0141] Example 6: Fractionation scheme 1 of soybean oil extract obtained according to Example 2: Fractionation conditions • Separation was performed on a Chromabond™ Flash RS 80 SiOH 40-63 μm column (Macherey-Nagel™ brand) with a column volume of 145 mL and a packing volume of 210 mL. Instructions for Use, Pages 14 / 17, CN 121285365 A

[0142] • The mobile phase is supplied using a pump at a flow rate of 5 mL / min.

[0143] • 14.6 g of soybean oil extract obtained according to Example 2 is dissolved in 40 mL of heptane.

[0144] • The obtained solution is deposited on top of the column using a pump at a flow rate of 5 mL / min.

[0145] • The column is then eluted with 400 mL of heptane.

[0146] • The column is then eluted with 800 mL of a heptane-dichloromethane mixture (1:1) (v / v).

[0147] • The column is then eluted with 500 mL of dichloromethane.

[0148] • The column is then eluted with 500 mL of a dichloromethane-methanol mixture (1:1) (v / v).

[0149] • The column is then eluted with 200 mL of methanol.

[0150] Scheme 2: UPLC-DAD Analysis Conditions • Column: BEH Shield 1.7 µm C18.150*2.1 mm • Mobile Phase: A: Water + 0.1% Formic Acid B: Acetonitrile + 0.1% Formic Acid • Gradient: According to Table 6 below [Table 6] • Column Temperature: 50℃ • Flow Rate: 0.4 mL / min • Detection: 205 nm and 234 nm • Injection Volume: 1 µL Scheme 3: CPG-MS Analysis Conditions • Column: DB-5HT (Agilent Technologies); 30 m × 0.32 mm × 0.1 µm • Injection: 320℃; Mode = Split • Furnace: According to the temperature gradient (℃) in Table 7 below [Table 7] • Carrier Gas Flow Rate: 1 mL / min • Detection: MS transfer line temperature = 350℃; ion source temperature = 320℃; MS-EI; full scan start mass = 40; full scan end mass = 800 • Injection Volume: 1µL Instructions 15 / 17 pages 18 CN 121285365 A Results: The fractions obtained were collected at the column outlet and analyzed by ultra-high pressure liquid chromatography (UPLC-DAD) coupled with a diode array detector and by gas chromatography (GC-MS) coupled with a mass spectrometer. They were then collected according to their composition and dried by vacuum evaporation.

[0151] Through this fractionation, four fractions were obtained 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), and then oxylipin (fraction 4, 8% by mass).

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

[0153] Table 8 below summarizes the results of testing the total lipid production induced by 10 μM arachidonic acid (AA) at 5 μg / mL using the soybean oil lipid extract prepared according to Example 2 and the different fractions obtained according to Example 6.

[0154] [Table 8] *: Corresponding to the oxylipin-rich extract according to the present invention, this experiment found that soybean oil has a strong sebum-regulating effect.

[0155] The free fatty acid and sterol fractions had little or no inhibition on lipid induction in arachidonic acid-stimulated sebaceous cells.

[0156] In the total lipid accumulation induced by arachidonic acid, fraction 4 with oxylipin was reduced much more than that of the unfractionated soybean oil extract, which clearly shows that the oxylipin fraction (oxidized fatty acids) of the soybean oil extract can strongly inhibit arachidonic acid-induced lipogenesis.

[0157] References FR2789085 Andreou et al., 2009, Lipids, 44: 207-215 Blée, 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. O: 220–246 Oenel et al., 2017, Plant Cell Physiol. 58(5): 925-933 Olah et al., 2014, J. Clin. Invest. 124(9), 3713-3724 Richardsonet al., 2017, J. Agric. Food Chem., 65: 1941-1951, Instructions for Use, 16 / 17 pages, 19 CN 121285365 A; Rustérucci et al., 1999, J Biol. Chem. Vol 274, N°51: 36446-36455; Van Ginneken et al., 2011, Lipids in Health and Disease, 10, 104, Instructions for Use, 17 / 17 pages, 20 CN 121285365 A; Figure 1, Figure 2, Instructions for Use, Figure 1 / 2 pages, 21 CN 121285365 A; Figure 3, Figure 4, Instructions for Use, Figure 2 / 2 pages, 22 CN 121285365 A

Claims

1. An oxylipin for use in the treatment of seborrhea.

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

3. The oxylipin for use according to claim 1 or 2, characterized in that, The oxylipin is selected from octadecanoids, eicosanoids and mixtures thereof.

4. The oxylipin for use according to any one of claims 1 to 3, characterized in that, The oxylipin is selected from the group consisting of 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,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 (12-13E-hydroperoxyarachidonic acid (15-HpETE) and mixtures thereof.

5. The oxylipin for use according to claim 4, characterized in that, 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 for use according to any one of claims 1 to 5, characterized in that, The oxylipin is present in an oxylipin-rich oleaginous plant extract.

7. The oxylipin for use according to claim 6, characterized in that, The oleaginous plant extract enriched in oxylipins is an extract of apple seeds, soybean, hazelnut or brown algae such as Saccharina latissima enriched in oxylipins Saccharina latissima gametophytes.

8. The oxylipin for use according to claim 6 or 7, characterized in that, The oxylipin-rich oleaginous plant extract contains at least 25% by weight, such as 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 the dry extract.

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

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

11. The composition for use according to claim 9 or 10, characterized in that, The at least one oxylipin is selected from octadecanoids, eicosanoids and mixtures thereof.

12. The composition for use according to any one of claims 9 to 11, characterized in that, The at least one oxylipin is selected from the group consisting of 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,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 (12-13E-hydroperoxyarachidonic acid (15-HpETE) and mixtures thereof.

13. The composition for use according to claim 12, characterized in that, 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 for use according to any one of claims 9 to 13, characterized in that, The at least one oxylipin is present in an oxylipin-rich oleaginous plant extract.

15. The composition for use according to claim 14, characterized in that, The oxylipin-rich oleaginous plant extract is an extract of an oxylipin-rich apple seed, soybean, hazelnut or brown algae such as Saccharina latissima gametophyte.

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