Process for obtaining inula helenium extracts and the use, in particular cosmetic use, thereof for skin care

Abstract

The present invention relates to processes for obtaining a plant extract of flowering tops of Inula helenium, and also to Inula helenium plant extracts, to compositions comprising same, and to the uses thereof for preventing and / or treating a chronic inflammatory skin disorder, in particular a pigmentary disorder, in particular (i) a pigmentary spot, in particular an actinic lentigo, (ii) a post-inflammatory hyperpigmentation, in particular associated with a scar or with an unaesthetic disorder consecutive to an inflammatory skin manifestation, in particular a scar or an acne mark, a scar or a rosacea mark or (iii) melasma.

Description

Process for obtainingInula heleniumextracts and the use, in particular cosmetic use, thereof for skin care

[0001] The present invention relates to the field of plant extracts, in particular derived fromInula helenium, and also to processes for obtaining such extracts and for using these extracts as active agents dedicated to caring for keratin materials, in particular the skin.Prior art

[0002] The skin is one of the largest and most complex organ systems in mammals, representing about 10% of the body weight. Under physiological conditions, it constitutes an essential protective barrier against external attacks while at the same time regulating the biological interactions between the organism and its environment. In addition to this mechanical barrier function, the skin is the site of complex biological mechanisms. In particular, it possesses the remarkable ability to activate an endogenous process known as “inflammation resolution”, which makes it possible to limit damage following an attack by promoting the cessation of inflammation, tissue repair and the return to tissue homeostasis.

[0003] This active process is based on cellular and molecular activities, in particular the polarization of pro-inflammatory (M1) macrophages to a pro-resolving state (M2), and the conversion of the production of pro-inflammatory molecules to anti-inflammatory and pro-resolving mediators called “Specialized Pro-Resolving Mediators”(SPMs). These mechanisms, although robust under normal conditions, may be disrupted in many chronic inflammatory skin disorders, such as actinic lentigo (AL) and liver spots.

[0004] AL is a hyperpigmented lesion associated with photoaging. Recent work has demonstrated the presence of persistent local microinflammation in these lesions, characterized by excessive infiltration of macrophages and T cells, in particular a significant increase in pro-inflammatory CD80+ / CD68+ (M1) macrophages to the detriment of pro-resolving (M2) macrophages. This imbalance in the M1 / M2 ratio reflects a chronic pro-inflammatory environment marked by the activation of the arachidonic acid cascade and the plasminogen pathway, leading to an excessive production of prostaglandins and a decrease in anti-inflammatory cytokines. As a consequence, the natural process for resolving inflammation is hindered, promoting the continuous recruitment of leukocytes and the degradation of surrounding tissues. This mechanism not only contributes to skin hyperpigmentation, but can also exacerbate skin aging and the risk of malignant transformation in some cases (Duvalet al., Scientific Reports, 14(1), 5256, (2024)).

[0005] A similar imbalance between M1 and M2 macrophages is observed in other chronic inflammatory skin disorders, in particular UV-induced skin aging also known as photoaging (Horibaet al., JID innovations, 2(3), 100112 (2022)), post-inflammatory hyperpigmentation, in particular hyperpigmentation associated with healing processes or unaesthetic disorders consecutive to inflammatory skin manifestations such as acne marks (Fenget al., Frontiers in immunology, 15, 1355455 (2024)).

[0006] Post-inflammatory hyperpigmentation (PIH) associated with scars or unaesthetic disorders consecutive to inflammatory skin manifestations, in particular acne marks or rosacea marks, is specifically a direct consequence of the inflammatory response in the skin. It results from an overproduction of melanin by melanocytes, stimulated by inflammatory mediators released during the healing of skin lesions. This excessive pigmentation is particularly common in cases of deep inflammatory acne marks or scars and may be aggravated by external factors, such as exposure to UV rays. Acne marks, which include atrophic and hypertrophic forms, are often associated with PIH, increasing the aesthetic and emotional impact on patients.

[0007] The treatment of PIH and acne scars is challenging, with conventional approaches focusing on reducing pigmentation (via depigmenting agents, chemical peels or lasers) or on improving structural scars (by tissue remodelling).

[0008] Despite the diversity of approaches available for treating these disorders, their effectiveness is often limited to the short term, and relapses are frequent after stopping treatments. Current treatments mainly include topical approaches, such as creams based on tretinoin or hydroquinone, aiming to reduce hyperpigmentation. These options may cause side effects, in particular skin irritation or increased UV sensitivity. In addition, more invasive procedures such as laser or cryotherapy are sometimes used, but they can lead to complications such as scars or post-inflammatory hyperpigmentation. These limitations highlight the importance of developing new, more effective and sustainable approaches for treating chronic inflammatory skin disorders such as pigmentary disorders and in particular pigmentary spots, such as actinic lentigo, post-inflammatory hyperpigmentation and melasma.

[0009] Thus, there remains a need to develop more effective, more specific and more sustainable solutions capable of naturally restoring skin homeostasis by promoting the resolution of skin inflammation.

[0010] Unexpectedly, the inventors have found that a specific plant extract ofInula helenium, and in particular a plant extract of flowering tops ofInula helenium, obtained bya process according to the invention, has properties particularly suitable for the resolution of inflammation in the skin. More precisely, this extract stimulates the polarization of macrophages towards a pro-resolving M2 phenotype and / or the shift of a pro-inflammatory M1 phenotype toward a pro-resolutive M2 phenotype and / or promotes the production of SPMs. These innovative features pave the way for a significant improvement in existing treatments. Thus, it is proposed to topically apply a composition containing such an extract, making it possible to actively promote the resolution of inflammation in the skin, by modulating the M1 / M2 ratio and stimulating pro-resolving mechanisms.

[0011] As a cosmetic ingredient, this specificInula heleniumextract offers an innovative approach for improving, in the short and long term, the prevention and / or treatment of the aforementioned disorders, in particular chronic inflammatory skin disorders, such as pigmentary disorders, in particular associated with inflammation, such as pigmentary spots, post-inflammatory hyperpigmentation, and melasma.

[0012] Moreover, the formulation of environmentally friendly cosmetic products, that is to say products of which the design and development take account of environmental issues, is becoming a major concern for contributing towards meeting global challenges. It is therefore essential to propose more sustainable compositions and / or preparation processes and / or ingredients, thus making it possible to respond to these environmental issues.

[0013] In this context, it is important to develop new ingredients and / or active agents that are environmentally conscious and are especially of natural origin, in particular biobased, and / or that are derived from sustainable sources that are not obtained from petrochemistry and / or that are biodegradable and / or the process for the extraction of which requires a low consumption of energy and water in order to provide compositions that enable a reduction in the environmental impact of the products.

[0014] There is thus a need for a new active agent, in particular cosmetic active agent, which makes it possible to stimulate the resolution of inflammation in the skin.

[0015] There is also a need for a new active agent, in particular cosmetic active agent, which makes it possible to promote the natural cessation of inflammation, tissue repair and a return to skin homeostasis.

[0016] There is also a need for a new active agent, in particular cosmetic active agent, which makes it possible to increase the secretion by the skin cells of several pro-resolving lipid mediators such as lipoxin A4, maresin 2, resolvin D1 and resolvin E4.

[0017] There is also a need for a novel active agent, in particular cosmetic active agent, which makes it possible, in macrophages at the skin level, to decrease the expression of pro-inflammatory genes, such as PTGS2 and / or TNF-α and / or to increase the expression of pro-resolving markers, such as CD206, CD209, AnXA1, PPARgamma and / or IL-10, and / or to increase the secretion by the skin cells of one or more pro-resolving lipid mediators, such as lipoxin A4, maresin 2, resolvin D1 and / or resolvin E4.

[0018] There is also a need for a novel active agent, in particular cosmetic active agent, which makes it possible to promote the polarization of macrophages into pro-resolving M2 macrophages at the skin level, either from non-polarized M0 macrophages or from inflammatory M1 macrophages (M1-M2 shift).

[0019] There is also a need for a novel active agent, in particular cosmetic active agent, which makes it possible to promote the polarization of macrophages into pro-resolving M2 macrophages, either from non-polarized M0 macrophages or from inflammatory M1 macrophages (M1-M2 shift) and / or to induce the production of SPMs at the skin level.

[0020] There is also a need for a novel active agent, in particular cosmetic active agent, which makes it possible to prevent and / or treat the signs of skin aging, in particular liver spots.

[0021] There is also a need for a new active agent, in particular cosmetic active agent, which makes it possible to offer short- and long-term treatment of pigmentary disorders such as actinic lentigo, but also of other inflammatory skin disorders such as post-inflammatory hyperpigmentation and melasma.

[0022] There is also a need for a new active agent, in particular cosmetic active agent, which makes it possible to offer short- and long-term treatment of chronic inflammatory skin disorders such as pigmentary disorders associated with inflammation, such as pigmentary spots, in particular actinic lentigo, which is also known as solar lentigo, or post-inflammatory hyperpigmentation, for example, associated with scars or unaesthetic disorders consecutive to an inflammatory skin manifestation, in particular scars or acne marks, scars or rosacea marks or melasma.

[0023] The present invention is directed precisely towards meeting all of these needs.Disclosure of the invention

[0024] The inventors have discovered, surprisingly, that a specificInula heleniumextract, obtained by a novel process according to the present application, effectively stimulates the resolution of skin inflammation by promoting the polarization of M2 macrophages and / or the shift of M1 macrophages toward an M2 phenotype and / or by inducing the production of SPMs (specialized pro-resolving mediators).

[0025] It has thus been demonstrated, as illustrated in the examples that follow, that such an extract, or a composition comprising it, makes it possible to support the process of resolution of skin inflammation, this process being important for the removal of inflammation, tissue repair and the return to skin homeostasis. This thus makes it possible to prevent and / or treat chronic inflammatory skin disorders, such as pigmentary disorders associated with inflammation, such as pigmentary spots (such as actinic lentigo), post-inflammatory hyperpigmentation, for example associated with scars or unaesthetic disorders consecutive to an inflammatory skin manifestation, in particular scars or acne marks, scars or rosacea marks or melasma.

[0026] By promoting the resolution of inflammation via M2 macrophages and SPMs, an extract according to the present invention specifically offers a double action: it supports tissue repair while at the same time reducing the processes responsible for PIH. This mechanism contributes to restoring healthy skin by minimizing pigmentary and structural marks left by inflammation.Summary of the invention

[0027] Thus, according to a first aspect, the present invention relates to a process for obtaining a plant extract of flowering tops ofInula helenium, comprising the steps consisting of:a) bringing at least one plant biomass comprising, and preferably consisting of, flowering tops ofInula heleniuminto contact with an extraction solvent comprising at least one cosmetically acceptable organic solvent,at an extraction temperature lower than the boiling point of the extraction solvent at atmospheric pressure,in particular, the duration of step a) being between 10 seconds and 5 hours; andb) removing the plant biomass residues, in particular by decantation and / or filtration.

[0028] According to a second aspect, the present invention relates to a process for obtaining a plant extract comprising, and preferably consisting of, flowering tops ofInula helenium, comprising the steps consisting of:a) bringing at least one plant biomass comprising, and preferably consisting of, flowering tops ofInula heleniuminto contact with an extraction solvent consisting of water at an extraction temperature of between 40°C and 90°C, in particular between 45°C and 85°C, and more particularly of about 50°C,in particular, the duration of step a) being between 10 seconds and 5 hours; andb) removing the plant biomass residues, in particular by decantation and / or filtration.

[0029] The plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniumof step a) of a process according to the invention may comprise, and may in particular be constituted of, flowering tops ofInula heleniumharvested at the full bloom stage, and in particular flowering tops ofInula heleniumharvested at the full bloom stage and dried and / or ground.

[0030] The plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniumof step a) may be dried during a step a’) prior to implementing step a), for at least about 24 hours, in particular about 72 hours, at a drying temperature of between 30°C and 60°C, in particular between 30°C and 50°C, more particularly between 30°C and 40°C, especially of about 35°C.

[0031] The plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniumof step a) may be ground during a step a’’) prior to implementing step a), with a particle size of between 2 cm and 0.1 mm, preferably between 1 cm and 0.5 mm, more particularly between 4 mm and 1 mm, in particular with a particle size of about 2 mm. Preferably, when step a’) and step a’’) are implemented, step a’) is carried out before step a’’).

[0032] Step a) of a process according to the invention may be an extraction step selected from a maceration step, an extrusion step or a percolation step, and is in particular a maceration step or an extrusion step.

[0033] Said at least one cosmetically acceptable organic solvent may be selected from polar protic organic solvents, polar aprotic organic solvents and apolar organic solvents, and mixtures thereof, it being understood that the solvents must be miscible with one another.

[0034] Among the polar protic organic solvents, mention may be made of i) polyols and glycols, and more particularly glycerol (glycerine), propanediol, butanediol, pentylene glycol, hexylene glycol, dipropylene glycol, tripropylene glycol, PPG-3 methyl ether, and PPG-2 butyl ether, ii) alcohols, and more particularly ethanol, isopropyl alcohol, t-butyl alcohol, phenethyl alcohol, caprylyl glycol, ethylhexylglycerol, and iii) mixtures thereof.

[0035] Among the polar aprotic organic solvents, mention may be made of i) esters, and more particularly triethyl citrate, acetyl tributyl citrate, ethyl acetate, propyl acetate, butyl acetate, amyl acetate, phenethyl benzoate, propylene glycol dibenzoate, C12-15 alkyl benzoate, ii) ketones, and more particularly acetone, iii) carbonates, and more particularly propylene carbonate, iv) amides, and more particularly ethyl tosylamide, v) dimethyl isosorbide, vi) fatty acids, and more particularly dilinoleic acid, and vii) mixtures thereof.

[0036] Among the apolar organic solvents, mention may be made of i) alkanes, and more particularly undecane, tridecane, C15-C19 alkanes, C9-12 alkanes, isohexadecane, isododecane, isoeicosane and ii) mixtures thereof.

[0037] The polar protic, aprotic and apolar organic solvents mentioned above may be used as a mixture, it being understood that said solvents must be miscible with one another.

[0038] Said at least one cosmetically acceptable organic solvent may be selected from the group consisting of polar protic organic solvents, such as ethanol, propanediol, glycerol, butanediol, and mixtures thereof; and / or from the group consisting of polar aprotic organic solvents, such as acetone, ethyl acetate, and mixtures thereof.

[0039] According to one embodiment, said at least one cosmetically acceptable organic solvent is selected from the group consisting of polar protic organic solvents and is preferably selected from ethanol, propanediol, glycerol, butanediol, and mixtures thereof.

[0040] According to another embodiment, said at least one cosmetically acceptable organic solvent is selected from the group consisting of polar aprotic organic solvents and is preferably selected from acetone, ethyl acetate, and mixtures thereof.

[0041] According to another embodiment, said at least one cosmetically acceptable organic solvent is selected from the group consisting of apolar organic solvents and is preferably isododecane.

[0042] The extraction solvent may additionally comprise water and the cosmetically acceptable organic solvent may be miscible with water.

[0043] Preferably, the extraction solvent consists of at least one water-miscible cosmetically acceptable organic solvent and water, the cosmetically acceptable organic solvent(s) and the water in particular being in a water:cosmetically acceptable organic solvent(s) ratio by weight of between 5:95 and 95:5, preferably 10:90 and 90:10, more preferentially between 15:85 and 85:15, even better still between 17:83 and 83:17, more particularly 70:30 or 20:80, in particular 50:50 or 60:40 or 80:20.

[0044] According to a preferred embodiment, the extraction solvent consists of at least one water-miscible cosmetically acceptable polar protic organic solvent and water, the cosmetically acceptable polar protic organic solvent(s) and the water in particular being in a water:cosmetically acceptable polar protic organic solvent(s) ratio by weight of between 5:95 and 95:5, preferably 10:90 and 90:10, more preferentially between 15:85 and 85:15, even better still between 17:83 and 83:17, more particularly 70:30 or 20:80, in particular 50:50 or 60:40 or 80:20.

[0045] The at least one cosmetically acceptable, preferably polar protic or aprotic, preferably polar protic, organic solvent may be present in the extraction solvent in a content of between 5% and 95% by weight relative to the total weight of the extraction solvent, preferably a content of between 10% and 90% by weight, more preferentially between 15% and 85% by weight, even better still between 17% and 83% by weight relative to the total weight of the extraction solvent.

[0046] The at least one cosmetically acceptable, preferably polar protic or aprotic, preferably polar protic, organic solvent may be present in the extraction solvent in a content of 100% by weight relative to the total weight of the extraction solvent. In this embodiment, the extraction solvent thus does not comprise water.

[0047] The extraction temperature of step a) of a process according to the first aspect of the invention is lower than the boiling point of said extraction solvent. The extraction temperature of step a) of a process according to the first aspect of the invention may be between 10°C and 95°C, preferably between 20°C and 95°C, especially between 40°C and 90°C, in particular between 45°C and 85°C, and is more particularly about 50°C or about 80°C; and / or the duration of step a) may be between 30 seconds and 3 hours, in particular between 1 minute and 2 hours, and more particularly between 90 seconds and 1 hour.

[0048] Step a) of a process according to the invention may be a maceration step, the extraction solvent comprising, and in particular consisting of, at least one cosmetically acceptable, preferably polar protic or aprotic, preferably polar protic, organic solvent, more particularly selected from ethanol, propanediol, and mixtures thereof, and optionally water, in particular consisting of water and at least one cosmetically acceptable, preferably polar protic, organic solvent, selected from ethanol, propanediol, and mixtures thereof, in particular in a water:[ethanol and / or propanediol] ratio by weight of greater than or equal to 20:80, in particular a water:[ethanol and / or propanediol] ratio by weight of about 30:70, 40:60, 50:50, 60:40, 70:30 or 80:20;the duration of step a) being between 10 minutes and 5 hours, in particular between 20 minutes and 1 hour; andthe extraction temperature being greater than or equal to 40°C, in particular being about 50°C or about 80°C.

[0049] Step a) of a process according to the invention may be an extrusion step, the extraction solvent comprising, and in particular consisting of, at least one cosmetically acceptable, preferably polar protic or aprotic, more preferentially polar protic, organic solvent, in particular selected from ethanol, glycerol, propanediol, and mixtures thereof, and optionally water, it being understood that, when the extraction solvent comprises water, the water:cosmetically acceptable organic solvent(s) ratio by weight is less than or equal to 1:1, and said cosmetically acceptable organic solvent is miscible with water;in particular, step a) may be carried out with anInula heleniumplant biomass:extraction solvent ratio by weight ranging between 1:2 and 1:5, in particular between 1:2.2 and 1:4, more particularly between 1:2.5 and 1:3, said ratio being in particular about 1:2.9; the duration of step a) being in particular less than 5 minutes; and the extraction temperature being between 40°C and 95°C, more preferentially between 45°C and 85°C, more preferentially still between 50°C and 85°C, and in particular being about 80°C.

[0050] When step a) is an extrusion step, the extraction solvent may consist of at least one cosmetically acceptable, preferably polar protic or aprotic, more preferentially protic, organic solvent, in particular selected from ethanol, glycerol, propanediol, and mixtures thereof, and optionally water, said extraction solvent preferably being selected from a mixture of water and of ethanol, a mixture of water and of propanediol, a mixture of water and of glycerol, or propanediol, it being understood that, when said extraction solvent comprises water, the cosmetically acceptable organic solvent(s) is miscible with water and the water:cosmetically acceptable organic solvent(s) ratio by weight is preferably between 5:95 and 1:1 such as 20:80, said extraction solvent preferably consisting of a water-propanediol mixture in a water:propanediol ratio by weight preferably of between 5:95 and 1:1 such as 20:80.

[0051] Step b) of removing the plant biomass residues of a process according to the invention may comprise at least one step b’) of decantation, optionally centrifugal decantation, the supernatant obtained at the end of the decantation step being isolated; and / or at least one step b’’) of filtration with at least one filter making it possible to obtain a filtrate, said filter(s) individually having a cut-off threshold of between 0.1 microns and 500 microns, in particular multiple filtration steps sequentially employing one or more filters, in particular with cut-off threshold(s) individually of between 50 microns and 500 microns and / or of between 0.1 microns and 25 microns, such as 0.2 microns.

[0052] A process according to the invention may additionally comprise a step c), after step b), b’) and / or b’’), of total or partial removal of the extraction solvent present in the filtrate obtained at the end of step b), b’) and / or b’’).

[0053] According to another aspect, the present invention relates to anInula heleniumplant extract obtained by a process according to the invention, said extract being in solid or liquid form.

[0054] The present invention also relates to a solid or liquidInula heleniumplant extract, in particular plant extract of flowering tops ofInula helenium, characterized in that it comprises:(i) optionally fumaric acid, and / or a salt thereof, in particular in a content of between 0.05% and 3.5% by weight relative to the total weight of dry matter in the plant extract;(ii) chlorogenic acid, and / or a salt thereof, in particular in a content of between 1.5% and 4% by weight relative to the total weight of dry matter in the plant extract;(iii) cryptochlorogenic acid, and / or a salt thereof, in particular in a content of between 0.25% and 1.5% by weight relative to the total weight of dry matter in the plant extract;(iv) neochlorogenic acid, and / or a salt thereof, in particular in a content of between 0.01% and 0.7% by weight relative to the total weight of dry matter in the plant extract;(v) 1,5-dicaffeoylquinic acid, and / or a salt thereof, in particular in a content of between 1.5% and 5% by weight relative to the total weight of dry matter in the plant extract;(vi) isochlorogenic acid B, and / or a salt thereof, in particular in a content of between 0.1% and 0.5% by weight relative to the total weight of dry matter in the plant extract;(vii) isochlorogenic acid A, and / or a salt thereof, in particular in a content of between 0.4% and 5% by weight relative to the total weight of dry matter in the plant extract;(viii) 4,5-dicaffeoylquinic acid, and / or a salt thereof, in particular in a content of between 0.1% and 6% by weight relative to the total weight of dry matter in the plant extract; and further comprises Costunolide; 2 alpha hydroxy alantolactone; 4,5-epoxy-10,14-dihydroinuviscolide; Dehydroivaxilin; 10-hydroxy-14H inuviscolide; 3-O-methylquercetin; Kaempferol 3-O-glucoside; Quercetin 3-O-glucoside; Hyperoside (quercetin 3-D-galactoside); Isorhamnetin 3-O-glucoside; 1,4-dicaffeoylquinic acid; 3,5-dicaffeoylquinic acid; Atractyligenin 2-O-glucoside; Kaempferol rutinoside; and / or 3,4,5-tricaffeoylquinic acid.

[0055] TheInula heleniumplant extract described above may additionally comprise:(ix) at least one polyphenol, and / or a salt thereof, in particular in a content of between 10% and 20% by weight relative to the total weight of dry matter in the plant extract, wherein the at least one polyphenol is different from chlorogenic acid; cryptochlorogenic acid; neochlorogenic acid; 1,5-dicaffeoylquinic acid; isochlorogenic acid B; isochlorogenic acid A; 4,5-dicaffeoylquinic acid; 1,4-dicaffeoylquinic acid; 3,5-dicaffeoylquinic acid; 3,4,5-tricaffeoylquinic acid; 3-O-methylquercetin; Kaempferol 3-O-glucoside; Quercetin 3-O-glucoside; Hyperoside (quercetin 3-D-galactoside); Isorhamnetin 3-O-glucoside and Kaempferol rutinoside; and / or(x) at least one (poly)amino acid; and / or(xi) at least one (poly)saccharide.

[0056] According to another aspect, the present invention also relates to a composition, in particular cosmetic composition, characterized in that it comprises, in a physiologically acceptable medium, at least oneInula heleniumplant extract according to the invention.

[0057] According to another aspect, the present invention also relates to the use of a plant extract according to the invention, or of a composition according to the invention, administered by oral or topical route, for preventing and / or treating a chronic inflammatory skin disorder, in particular selected from the group consisting of:a pigmentary disorder, in particular (i) a pigmentary spot, in particular an actinic lentigo, (ii) post-inflammatory hyperpigmentation, in particular associated with a scar or with an unaesthetic disorder consecutive to an inflammatory skin manifestation, in particular a scar or an acne mark, a scar or a rosacea mark or (iii) melasma.

[0058] In the context of this use, the composition according to the invention may be presented in the form of a food supplement, in particular as soft capsules or capsules, banded capsules, dragees, syrup, gummies, gels, dry or liquid emulsions, tablets, powders for reconstitution, or drinkable ampoules, or as an enriched food product.

[0059] In the context of this use, the composition according to the invention may further comprise at least one edible excipient selected from colorants, sweeteners, bulking agents, binders, and preservatives.

[0060] According to another aspect, the present invention also relates to a process for the cosmetic treatment of a keratin material, comprising the application, in particular topical application, to said keratin material of a plant extract according to the invention, or of a composition according to the invention.Detailed descriptionDefinitions

[0061] “Inula helenium”, also known as elecampane, is a perennial plant belonging to the family Asteraceae.

[0062] In the context of the present invention, the term “plant biomass” denotes all of the materials of plant origin after picking, in particular the aerial parts of a plant. This biomass may be used in the fresh state, dried, wilted, in whole form, more or less finely cut, or ground.

[0063] The term “dry plant biomass” is understood to mean a plant biomass from which the water naturally present has been removed; preferably, the moisture content, that is to say the water content, is between 0% and 10%, preferably less than 5%, more preferentially still less than 4%, better still less than 3%, for example less than 2% by weight relative to the total weight of, optionally ground, plant biomass.

[0064] The term “fresh plant biomass” is understood to mean a plant biomass from which the water present in the natural state has not been removed; it has preferably been harvested a few hours to a few days (up to 15 days) before being brought into contact with the extraction solvent and stored at a compatible temperature and at a relative humidity allowing its water content to be maintained with a maximum variation of ± 2% water. Preferably, the fresh plant biomass has a water content of greater than 10% by weight relative to the total weight of, optionally ground, plant biomass.

[0065] The term “wilted plant biomass” is understood to mean a plant biomass which corresponds to a fresh plant biomass stored for one to several days (up to 15 days) before being used in the process according to the invention.

[0066] According to the invention, a “physiologically acceptable medium” is a medium which is odourless and has no unpleasant taste or appearance, and which is perfectly compatible with the administration route under consideration, in particular the topical route or the oral route, i.e. which has a pleasant colour and feel and does not generate any unacceptable discomfort, i.e. tingling, tautness or redness, liable to discourage the user from applying this composition. A physiologically acceptable medium is preferentially a cosmetically acceptable medium.

[0067] According to the invention, the term “cosmetically acceptable organic solvent” is understood to mean, for the purposes of the present invention, a solvent which comprises carbon atoms, hydrogen atoms and optionally one or more heteroatoms preferably selected from oxygen, nitrogen and sulfur atoms, compatible with the administration route under consideration, in particular the topical route or the oral route.

[0068] The term “polar organic solvent” is understood to mean a solvent which comprises carbon atoms, hydrogen atoms and one or more heteroatoms preferably selected from oxygen and nitrogen atoms. In particular, the polar organic solvent(s) are composed of atoms with different electronegativities and the difference in electronegativity of between 0.4 and 1.7, forming polarized bonds between them.

[0069] For the purposes of the present invention, the term “polar protic organic solvent” is understood to mean a solvent which comprises carbon atoms, hydrogen atoms and one or more heteroatoms preferably selected from oxygen atoms and nitrogen atoms, the solvent comprising atoms possessing a hydrogen atom bonded to a strongly electronegative atom (such as oxygen, or nitrogen) and capable of forming hydrogen bonds. This ability to form hydrogen bonds results from the presence of proton-donating functional groups, mainly hydroxyl (-OH) and amine (-NH₂) groups. The polarity of the solvent comes from the significant difference in electronegativity between the hydrogen atom and the electronegative atom to which it is bonded, creating a molecular dipole. Thus, a polar protic solvent has the ability to release acidic H+ ions or to create hydrogen bonds.

[0070] For the purposes of the present invention, the term “polar aprotic organic solvent” is understood to mean a solvent which comprises carbon atoms, hydrogen atoms and one or more heteroatoms preferably selected from oxygen atoms and nitrogen atoms; however, in contrast to protic solvents, a polar aprotic solvent does not possess any hydrogen atom attached to a strongly electronegative atom (such as oxygen in a hydroxyl -OH group or nitrogen in an amine -NH group). Consequently, it cannot donate a proton (H+) to form a hydrogen bond. However, it can accept protons by virtue of the presence of free electron pairs on the heteroatom, thus participating in hydrogen bonds as an acceptor. The absence of hydroxyl or amine groups is therefore a key element of its definition.

[0071] For the purposes of the present invention, the term “apolar organic solvent” is understood to mean a solvent composed essentially of carbon and hydrogen which possesses low polarity or no polarity at all. This means that the distribution of the electric charge in the molecule is symmetrical, or almost symmetrical, resulting in a zero or very small dipole moment.

[0072] The term “miscible” is understood to mean the ability of two or more substances to mix and form a homogeneous solution at ambient temperature (25°C) and at atmospheric pressure; in other words, miscible substances dissolve in one another in any proportion without phase separation.

[0073] The term “dry extract” is understood to mean a plant extract obtained after removal of the extraction solvent. Preferably, the dry extract comprises less than 10% by weight, preferably less than 5% by weight, preferably less than 3% by weight, preferably less than 1% by weight, preferably less than 0.5% by weight, relative to the total weight of extract, of extraction solvent. Preferably, the dry extract is free of extraction solvent.

[0074] The terms “dry extract” and “solid extract” are used interchangeably here.

[0075] The term “liquid extract” is understood to mean a plant extract for which the extraction solvent is retained or not completely removed. Preferably, the liquid extract comprises a content of greater than 10% by weight, relative to the total weight of extract, of extraction solvent.

[0076] For the purposes of the present application, a “water:cosmeticallyacceptable organic solvent(s) ratio by weight” refers to the weight ratio of the amount of water relative to the total amount of cosmetically acceptable organic solvent(s) present in the extraction solvent. Consequently, this ratio is expressed as weight / weight (w / w).

[0077] In the context of the invention, the term “plant biomass of flowering tops ofInula helenium” is understood to mean anInula heleniumbiomass comprising flowering tops ofInula heleniumand preferably a biomass constituted of flowering tops ofInula helenium.

[0078] The terms “Inula heleniumplant biomass”, “Inula heleniumbiomass”, and “plant biomass of flowering tops ofInula helenium” are equivalent for the purposes of the invention.

[0079] In the context of the present invention, an “Inula helenium plantbiomass:extractionsolventratio by weight” refers to the proportion by mass between the plant biomass and the amount of extraction solvent employed during the extraction step. Consequently, this ratio is expressed as weight / weight (w / w). This ratio can also be expressed in the form of a range of values, for example from 1:2 to 1:5, meaning that, for each unit by weight ofInula heleniumplant biomass, an amount of extraction solvent ranging between 2 and 5 units by weight is employed.

[0080] For the purposes of the present invention, the term “keratin materials” is understood in particular to denote the skin, the lips, the eyelashes and / or the hair, in particular the skin and / or the lips, and preferably the skin of the body, including, inter alia, the skin of the scalp, of the face, of the neck, of the arms and of the hands.

[0081] The term “skin" is understood to mean all of the skin of the body, including the scalp.

[0082] The present invention relates to the use of an extract and / or a composition according to the invention on healthy skin.

[0083] “Healthy skin” denotes, in the context of the present invention, skin which does not exhibit a proven pathological state, such as dermatitis, psoriasis or active skin infection. However, the concept of healthy skin includes skin conditions that may exhibit aesthetic or functional imperfections, such as pigmentary spots, scars, rosacea marks or a tendency towards acne marks.

[0084] Thus, in the cosmetic context of the invention, healthy skin corresponds to skin the appearance and functions of which can be optimized without curative medical treatment, but by care intended to improve the aesthetics, comfort and / or overall balance thereof.

[0085] The term “post-inflammatory hyperpigmentation”is understood to mean post-inflammatory hyperpigmentation associated with healing processes, in particular associated with post-lesion healing following, for example, pimples such as acne pimples, irritations, rubbing, insect bites or stings, but also post-inflammatory hyperpigmentation consecutive to treatments of the skin with electromagnetic devices (such as ultrasound, radiofrequency, laser, pulsed flash lamp), microdermabrasion, chemical peels or cryotherapy.

[0086] “Actinic lentigo” or “solar lentigo”, or “liver spot”, or “senile lentigo”, is understood to mean a small, flat, pigmented spot that appears on skin subjected to chronic sun exposure, mainly in people over 40 years old. It is a benign skin lesion that represents a marker of skin photoaging.

[0087] The term “melasma” is understood to mean a common and benign acquired hyperpigmentation of the skin, which is characterized by the appearance of symmetrical brown or grey-brown spots on the face. It is sometimes called the “mask of pregnancy” or “chloasma”.

[0088] In the context of the present invention, the terms “prevent” and “prevention” denote the reduction, to a lesser extent, of the risk or probability of occurrence of a given phenomenon.

[0089] As used in the present invention, the terms “treat” and “treatment” denote the alleviation of the symptoms associated with a disorder or a specific condition and / or the elimination of said symptoms, and also the complete disappearance of the disorder or condition in question. In the context of the present invention, this is understood in particular to mean the treatment of chronic inflammatory skin disorders, in particular a skin disorder selected from the group consisting of a pigmentary disorder, in particular (i) a pigmentary spot, in particular an actinic lentigo, or post-inflammatory hyperpigmentation, in particular associated with a scar or with an unaesthetic disorder consecutive to an inflammatory skin manifestation, in particular a scar or an acne mark, a scar or a rosacea mark or (iii) melasma.

[0090] Melasma is a skin affliction characterized by the appearance of hyperpigmented, generally symmetrical spots on areas exposed to the sun, such as the face, resulting from the localized increase in melanin production.

[0091] Moreover, the expression “at least one” used in the present description is equivalent to the expression “one or more”.

[0092] For the purposes of the present invention and unless indicated otherwise, the limits of a range of values are included within that range, especially in the expressions “between” and “ranging from ... to ...”.

[0093] For a numerical value, the term “about” is understood to mean this numerical value plus or minus a percentage of less than 10%, in particular less than or equal to 5%, especially less than or equal to 2%, more particularly less than or equal to 1%.

[0094] Units, prefixes and symbols are designated in their form accepted by the International System of Units (SI).

[0095] The headings provided in the application are not limitations on the various aspects of the disclosure.

[0096] Process for obtaining a plant extract according to the invention

[0097] As indicated above, the present invention relates to processes for obtaining a plant extract of flowering tops ofInula helenium.

[0098] Plant extraction is a solid / liquid separation process that aims to isolate certain compounds present in the plants. It consists in bringing a solid material, such as plant biomass, here the flowering tops ofInula helenium, into contact with an extraction solvent. The targeted compounds dissolve in the solvent, forming a solution which, after decantation and / or filtration, constitutes the desired plant extract.

[0099] These processes thus comprise a step a) of bringing at least one plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniuminto contact with an extraction solvent.Inula helenium plant biomass

[0100] A plant biomass employed in a step a) of a process according to the invention can be obtained fromInula heleniumplants grown in their natural habitat or, more particularly, from cultivated plants.

[0101] AnInula heleniumplant biomass according to the invention is a plant biomass comprising, and preferably consisting of, flowering tops ofInula helenium.

[0102] It may therefore involve more or less extensive aerial parts, containing flowering tops or consisting of flowering tops ofInula helenium.

[0103] The term “aerial parts” is understood to denote the above-ground portions of the plant, including stems, leaves, buds and flowers, in particular flowers at the full-bloom stage, possibly accompanied by flowers at the end of flowering or in the flower-bud state. In particular, the aerial parts do not include the roots or the rhizomes of the plant.The term “flowering tops” is understood to denote the aerial part of the harvested plant starting from the lowest flower, that is to say the flower situated at the position closest to the ground, up to the upper end of said plant. The flowering tops include flowers, in particular flowers at the full bloom stage, possibly accompanied by flowers at the end of flowering or in the flower-buds state, leaves and stems. In particular, the flowering tops do not include the roots or rhizomes of the plants. More particularly, the flowering tops preferably comprise at least flowers, preferentially flowers at the full bloom stage, stems and leaves, and more particularly comprise or even consist of flowers, in particular predominantly flowers in full bloom, leaves, preferably included between the different flower levels, and stems, preferably included between the different flower levels.

[0104] “Full bloom” denotes the state of a flower when it has reached its maximum development. At this stage, its petals are fully deployed, often revealing the internal structures such as the stamens and the pistil, and it usually exhibits its most striking colours and shape.

[0105] According to a particular embodiment, the flowering tops ofInula heleniumare harvested at the full bloom stage, preferably between mid-June and mid-July.

[0106] According to a particular embodiment, the flowering tops ofInula heleniumare harvested at the full bloom stage between mid-June and mid-July.

[0107] According to one embodiment, theInula heleniumplant biomass may be fresh, dried, wilted, or a mixture. Preferably, theInula heleniumplant biomass is dried.

[0108] According to one embodiment, theInula heleniumplant biomass employed in a process according to the invention is put to dry within 72 hours of its harvest.

[0109] According to one embodiment, the plant biomass is dried at a drying temperature of between 30°C and 60°C. With preference, the plant biomass is dried at a drying temperature of between 30°C and 50°C, even better still at a drying temperature of between 30°C and 40°C. Preferably, the drying temperature is about 35°C. The drying time can be from about 24 hours to 1 week, preferably from about 24 hours to about 72 hours. Preferably, the moisture content, that is to say the water content of the biomass after drying of the biomass, is between 0% and 10%, preferably less than 5%, more preferentially still less than 4%, even better still less than 3% and for example less than 2% by weight relative to the total weight of plant biomass.

[0110] A well-known method of drying consists in using a hot air dryer, in which the plant biomass is exposed to a stream of air at a controlled temperature, enabling the gradual evaporation of the water. Another commonly used approach is vacuum drying, which reduces the pressure around the biomass in order to facilitate the removal of moisture at lower temperatures, thus preserving heat-sensitive compounds. Drying by freeze-drying is also an appropriate method, in particular when it is desired to preserve the structure and the bioactive properties of the biomass. This technique involves prior freezing of the biomass followed by sublimation of the water under vacuum. Another method is to let the biomass dry in the open air on trays.

[0111] According to another embodiment, the fresh, dried or wiltedInula heleniumplant biomass employed in a process according to the invention is ground, and possibly cryogenically ground.

[0112] A well-known method of grinding consists in using a mechanical blade mill, also referred to as a knife mill. This type of mill operates by cutting the plant biomass into fine particles using rotating blades. Alternatively, a hammer mill can be used. This device fragments the biomass by applying a repeated impact force, producing particles of homogeneous size. Another commonly used approach is attrition milling, carried out using disc mills, where the biomass is reduced by friction between abrasive surfaces. These methods make it possible to adjust the particle size according to the needs of the process.

[0113] Advantageously, cryogenic grinding is a particularly suitable method for preserving the bioactive properties of heat-sensitive compounds. The technique consists in cooling the plant biomass using a cryogenic gas, such as liquid nitrogen, prior to and / or during the grinding. The extreme cooling weakens the plant structures and facilitates the fragmentation thereof into fine particles, while at the same time limiting the thermal degradation of volatile or thermolabile compounds. Cryogenic grinding thus makes it possible to obtain a controlled particle size, while at the same time preserving the chemical and biological characteristics of the biomass.

[0114] The grinding may be coarse (of the order of a centimetre) or fine (of the order of a millimetre). Preferably, theInula heleniumplant biomass is ground with a particle size of between 2 cm and 0.1 mm, preferably between 1 cm and 0.5 mm, more particularly between 4 mm and 1 mm, in particular with a particle size of about 2 mm.

[0115] According to one embodiment, theInula heleniumplant biomass is:- dried and ground; or- cryogenically ground.

[0116] According to another embodiment, theInula heleniumplant biomass is dried and then ground, preferably dried and then ground to a particle size of between 2 cm and 0.1 mm, preferably between 1 cm and 0.5 mm, more particularly between 4 mm and 1 mm, in particular with a particle size of about 2 mm.

[0117] According to another embodiment, theInula heleniumplant biomass is prechopped, dried and then ground, preferably prechopped, dried and then ground to a particle size of between 2 cm and 0.1 mm, preferably between 1 cm and 0.5 mm, more particularly between 4 mm and 1 mm, in particular with a particle size of about 2 mm.

[0118] According to one embodiment, the plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniumof step a) of a process according to the invention has been dried during a step a’) prior to implementing step a), at a drying temperature of between 30°C and 60°C for at least 24 hours, in particular of between 30°C and 50°C, especially between 30°C and 40°C, more particularly of about 35°C.

[0119] According to one embodiment, the plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniumof step a) of a process according to the invention has been ground during a step a’’) prior to implementing step a), with a particle size of between 2 cm and 0.1 mm, preferably between 1 cm and 0.5 mm, more particularly between 4 mm and 1 mm, in particular with a particle size of about 2 mm.

[0120] More particularly, the plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniumof step a) of a process according to the invention has been:- dried during a step a’) prior to implementing step a), at a drying temperature of between 30°C and 60°C for at least 24 hours, in particular of between 30°C and 50°C, especially between 30°C and 40°C; and in particular then- has been ground during a step a’’) prior to implementing step a), with a particle size of between 2 cm and 0.1 mm, preferably between 1 cm and 0.5 mm, more particularly between 4 mm and 1 mm, in particular with a particle size of about 2 mm.

[0121] Preferably, when step a’) and step a’’) are implemented, step a’ is carried out prior to step a’’).

[0122] As indicated above, step a) of a process according to the invention comprises bringing at least one plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniuminto contact with an extraction solvent.Extraction solvent

[0123] Step a) of a process according to the invention is carried out at an extraction temperature lower than the boiling point of the extraction solvent at atmospheric pressure.

[0124] According to one embodiment, the extraction temperature may be greater than or equal to 40°C, it being understood that the extraction temperature must be lower than the boiling point of the solvent at atmospheric pressure.

[0125] According to another embodiment, step a) is carried out at an extraction temperature of between 10°C and 95°C, preferably between 20°C and 95°C, more preferentially between 40°C and 90°C, even better still between 45°C and 85°C, better even still between 50°C and 85°C, it being understood that the extraction temperature must be lower than the boiling point of the solvent at atmospheric pressure. In particular, the extraction temperature may be about 50°C, about 80°C or about 95°C.

[0126] According to another embodiment, step a) is carried out without heating, that is to say at ambient temperature, i.e. about 25°C.

[0127] According to a first embodiment, an extraction solvent of a process according to the invention comprises at least one cosmetically acceptable organic solvent.

[0128] The term “cosmetically acceptable organic solvent” denotes an organic solvent compatible with use, in particular oral use, or topical use on keratin materials, in particular on the skin, which satisfies the safety and tolerance requirements in force in the cosmetics field. Such a solvent should be non-irritating, non-sensitizing and non-toxic under normal conditions of use. Furthermore, the cosmetically acceptable organic solvent must not degrade the efficacy or the stability of the active agents or of the cosmetic formulations in which it is incorporated.

[0129] According to one embodiment, step a) is carried out with a [plant biomass comprising, and in particular consisting of, flowering tops ofInula helenium]:extraction solvent ratio by weight ranging between 1:2 and 1:100, in particular between 1:2.2 and 1:20, more particularly between 1:2.5 and 1:15. Said ratio may in particular be about 1:10. According to another embodiment, step a) is carried out with a [plant biomass comprising, and in particular consisting of, flowering tops ofInula helenium]:extraction solvent ratio by weight ranging between 1:2 and 1:5, in particular between 1:2.2 and 1:4, more particularly between 1:2.5 and 1:3. Said ratio is more preferentially about 1:2.9 or about 1:2.

[0130] A cosmetically acceptable organic solvent employed in a process according to the invention may be selected from polar aprotic organic solvents, polar protic organic solvents, apolar organic solvents, and mixtures thereof, it being understood that the solvents must be miscible with one another.

[0131] Among the polar protic organic solvents, mention may be made of i) polyols and glycols, and more particularly glycerol (glycerine), propanediol, butanediol, pentylene glycol, hexylene glycol, dipropylene glycol, tripropylene glycol, PPG-3 methyl ether, and PPG-2 butyl ether, ii) alcohols, and more particularly ethanol, isopropyl alcohol, t-butyl alcohol, phenethyl alcohol, caprylyl glycol, ethylhexylglycerol, and iii) mixtures thereof.

[0132] Thus, said at least one cosmetically acceptable organic solvent may be selected from the group consisting of polar protic organic solvents, such as ethanol, propanediol, glycerol, butanediol, and mixtures thereof; and / or from the group consisting of polar aprotic organic solvents, such as acetone, ethyl acetate, and mixtures thereof.

[0133] According to one embodiment, said at least one cosmetically acceptable organic solvent is selected from the group consisting of polar protic organic solvents and is preferably selected from ethanol, propanediol, glycerol, butanediol, and mixtures thereof.

[0134] Among the polar aprotic organic solvents, mention may be made of i) esters, and more particularly triethyl citrate, acetyl tributyl citrate, ethyl acetate, propyl acetate, butyl acetate, amyl acetate, phenethyl benzoate, propylene glycol dibenzoate, C12-15 alkyl benzoate, ii) ketones, and more particularly acetone, iii) carbonates, and more particularly propylene carbonate, iv) amides, and more particularly ethyl tosylamide, v) dimethyl isosorbide, vi) fatty acids, and more particularly dilinoleic acid, and vii) mixtures thereof.

[0135] Among the apolar organic solvents, mention may be made of i) alkanes, and more particularly undecane, tridecane, C15-C19 alkanes, C9-12 alkanes, isohexadecane, isododecane, isoeicosane and ii) mixtures thereof.

[0136] Thus, according to another embodiment, said at least one cosmetically acceptable organic solvent is selected from the group consisting of polar aprotic organic solvents and is preferably selected from acetone, ethyl acetate, and mixtures thereof.

[0137] According to another embodiment, said at least one cosmetically acceptable organic solvent is selected from the group consisting of apolar organic solvents and is preferably isododecane.

[0138] The polar protic, aprotic and apolar organic solvents mentioned above may be used as a mixture, it being understood that said solvents must be miscible with one another.

[0139] According to one embodiment, the cosmetically acceptable polar organic solvent is a polar aprotic organic solvent.

[0140] A polar aprotic organic solvent suitable for use in the invention is preferably selected from acetone, ethyl acetate, propyl acetate, butyl acetate, amyl acetate, and mixtures thereof.

[0141] According to one embodiment, the cosmetically acceptable organic solvent(s) are a mixture of at least one polar protic solvent and of at least one polar aprotic solvent such as a mixture of acetone with at least one solvent selected from ethanol, glycerol, propanediol, butanediol and mixtures thereof, in particular a mixture of acetone with at least one solvent selected from ethanol, propanediol and mixtures thereof.

[0142] According to a preferred embodiment, the cosmetically acceptable organic solvent is a polar protic organic solvent.

[0143] A polar protic organic solvent suitable for use in the invention is preferably selected from ethanol, glycerol, propanediol, butanediol, and mixtures thereof, in particular from ethanol, propanediol, and mixtures thereof.

[0144] The extraction solvent may comprise, and in particular be constituted of, several polar aprotic solvents, preferably comprising and more particularly being constituted of acetone.

[0145] According to one embodiment, the extraction solvent comprises at least one cosmetically acceptable organic solvent and optionally water, it being understood that when the extraction solvent comprises water then the organic solvent is miscible with water, in particular a polar aprotic organic solvent, and optionally water, more particularly acetone and optionally water.

[0146] According to one embodiment, the extraction solvent is constituted of at least one cosmetically acceptable organic solvent and optionally water, it being understood that when the extraction solvent comprises water then the organic solvent is miscible with water, in particular a polar aprotic organic solvent, and optionally water, more particularly acetone and optionally water, and better still is constituted of acetone.

[0147] According to one embodiment, the extraction solvent comprises at least one cosmetically acceptable organic solvent, in particular a water-miscible polar aprotic organic solvent, and water, more particularly acetone and water.

[0148] The extraction solvent may comprise, and in particular be constituted of, several polar protic solvents selected from ethanol, glycerol, propanediol and butanediol, in particular from ethanol and propanediol, it being possible for said extraction solvent to also contain one or more polar aprotic solvents preferably selected from acetone, said extraction solvent more preferentially not containing any polar aprotic solvents.

[0149] Thus, according to one embodiment, an extraction solvent does not comprise any polar aprotic solvents.

[0150] The extraction solvent may comprise, and in particular be constituted of, several polar protic solvents selected from ethanol, glycerol, propanediol and butanediol, in particular from ethanol and propanediol.

[0151] According to one embodiment, the at least one cosmetically acceptable organic solvent, preferably a polar protic organic solvent, is present in the extraction solvent in a content of 100% by weight relative to the total weight of the extraction solvent.

[0152] Thus, the extraction solvent may be constituted of ethanol, glycerol, propanediol or butanediol, more particularly ethanol or propanediol. In particular, the extraction solvent may be constituted of propanediol.

[0153] According to another embodiment, the extraction solvent comprises at least one cosmetically acceptable organic solvent, in particular a polar protic organic solvent, and water.

[0154] In the presence of water, the at least one cosmetically acceptable organic solvent is miscible with water.

[0155] In particular, the polar protic organic solvent is selected from ethanol, propanediol, glycerol, and mixtures thereof.

[0156] Preferably, the extraction solvent comprises, and in particular is constituted of, ethanol and water, propanediol and water, or glycerol and water. According to one embodiment, the extraction solvent comprises, and in particular is constituted of, ethanol and water. According to another embodiment, the extraction solvent comprises, and in particular is constituted of, propanediol and water.

[0157] Said at least one cosmetically acceptable organic solvent may be present in the extraction solvent in a content of between 5% and 95% by weight relative to the total weight of the extraction solvent, preferably a content of between 10% and 90% by weight, more preferentially between 15% and 85% by weight, even better still between 17% and 83% by weight relative to the total weight of the extraction solvent.

[0158] According to one embodiment, when the extraction solvent comprises water, the water:cosmetically acceptable organic solvent(s) ratio by weight is less than or equal to 1:1.

[0159] According to one embodiment, when the extraction solvent comprises water, the water:cosmetically acceptable organic solvent(s) ratio by weight is between 5:95 and 95:5, preferably between 10:90 and 90:10, more preferentially between 15:85 and 85:15, even better still between 17:83 and 83:17, and may in particular be 20:80, 70:30, 30:70, 40:60, 50:50, 60:40, 70:30 or 80:20.

[0160] Thus, according to a preferred embodiment, the extraction solvent consists of at least one water-miscible cosmetically acceptable polar protic organic solvent and water, the cosmetically acceptable polar protic organic solvent(s) and the water in particular being in a water:cosmetically acceptable polar protic organic solvent(s) ratio by weight of between 5:95 and 95:5, preferably 10:90 and 90:10, more preferentially between 15:85 and 85:15, even better still between 17:83 and 83:17, more particularly 70:30 or 20:80, in particular 50:50 or 60:40 or 80:20.

[0161] According to one embodiment, the water:[ethanol and / or propanediol] ratio by weight is greater than or equal to 20:80; in particular, the water:[ethanol and / or propanediol] ratio by weight is about 20:80, 30:70, 40:60, 50:50, 60:40, 70:30 or 80:20.

[0162] According to one embodiment, the extraction solvent is constituted of water and ethanol in a water:ethanol ratio by weight of 70:30 or 60:40. Preferably, the water:ethanol ratio by weight is 70:30.

[0163] According to another embodiment, the extraction solvent is constituted of water and propanediol in a water:propanediol ratio by weight preferably of between 5:95 and 1:1. In particular, the water:propanediol ratio by weight is 20:80, 30:70 or 50:50. Preferably, the water:propanediol ratio by weight is 20:80.

[0164] According to a second embodiment, an extraction solvent of a step a) of a process according to the invention consists of water at an extraction temperature of between 40°C and 90°C, in particular between 45°C and 85°C, the extraction temperature more particularly being about 50°C.

[0165] According to one embodiment, the extraction duration of step a) is between 10 seconds and 5 hours, with a preference for an extraction duration of between 30 seconds and 3 hours, more preferentially between 1 minute and 2 hours, and more particularly still between 90 seconds and 1 hour. According to one embodiment, the extraction duration is less than 5 minutes. According to another embodiment, the extraction duration is about 1 hour or 2 hours.

[0166] According to one embodiment, the extraction temperature of step a) is between 10°C and 95°C, preferably 20°C and 95°C, especially between 40°C and 90°C, in particular between 45°C and 85°C, and is more particularly about 50°C or about 80°C; and / or the duration of step a) is between 30 seconds and 3 hours, in particular between 1 minute and 2 hours, and more particularly between 90 seconds and 1 hour.

[0167] According to one embodiment, step a) of a process according to the invention is implemented:- at an extraction temperature of between 40°C and 90°C, in particular between 45°C and 85°C, and more particularly at an extraction temperature of about 50°C; and- for a duration of between 10 seconds and 5 hours.

[0168] According to one embodiment, step a) of a process according to the invention is implemented:

[0169] - at an extraction temperature of between 40°C and 90°C, in particular between 45°C and 85°C, and more particularly at an extraction temperature of about 50°C or of about 80°C; and / or

[0170] - for a duration of between 30 seconds and 3 hours, in particular between 1 minute and 2 hours, and more particularly between 90 seconds and 1 hour.

[0171] As indicated above, step a) of a process according to the invention may be an extraction step selected from a maceration step, an extrusion step or a percolation step, and is in particular a maceration step or an extrusion step.

[0172] According to one embodiment, the extraction step is a maceration step.

[0173] According to one embodiment, the maceration step is carried out by a static action such as by microwaves and / or ultrasound, and / or by a mechanical action such as stirring, and / or trituration and / or shearing. Preferentially, the maceration step is carried out without the use of microwaves or ultrasound. In particular, the maceration step is carried out by stirring without the use of microwaves or ultrasound.

[0174] According to one embodiment, the maceration step is carried out by mechanical stirring with the aid of a stirring blade. The stirring speed is advantageously between 50 and 500 rpm, more preferably between 50 and 300 rpm, and more preferably still between 200 and 300 rpm.

[0175] According to one embodiment, the extraction solvent used during the maceration step comprises, and in particular consists of, at least one cosmetically acceptable, preferably polar protic, organic solvent, selected from ethanol, propanediol, and mixtures thereof, and optionally water.

[0176] According to another embodiment, the extraction solvent used during the maceration step consists of water and at least one cosmetically acceptable, preferably polar protic, organic solvent, selected from ethanol, propanediol, and mixtures thereof. In particular, the extraction solvent used during the maceration step comprises, and in particular consists of, water and ethanol and / or propanediol in a water:[ethanol and / or propanediol] ratio by weight of greater than or equal to 20:80, in particular a water:[ethanol and / or propanediol] ratio by weight of about 30:70, 40:60, 50:50, 60:40, 70:30 or 80:20.

[0177] According to one embodiment, the extraction solvent used during the maceration step consists of water and ethanol in a water:ethanol ratio by weight of about 70:30 or 60:40. According to another embodiment, the extraction solvent used during the maceration step consists of water and propanediol in a water:propanediol ratio by weight of about 20:80, 30:70 or 50:50.

[0178] According to one embodiment, the extraction solvent used during the maceration step consists of propanediol.

[0179] According to one embodiment, the duration of the maceration step is between 10 minutes and 5 hours, in particular between 20 minutes and 1 hour. According to one embodiment, the duration of the maceration step is about 1 hour or about 2 hours.

[0180] According to one embodiment, the maceration step is carried out at an extraction temperature of greater than or equal to 40°C, in particular of about 50°C or of about 80°C.

[0181] According to one embodiment, the maceration step is carried out with a [plant biomass comprising, and in particular consisting of, flowering tops ofInula helenium]:extraction solvent ratio by weight ranging between 1:2 and 1:100, in particular between 1:2.2 and 1:20, more particularly between 1:2.5 and 1:15.

[0182] Preferably, in an embodiment in which step a) of a process according to the invention is a maceration step, the [plant biomass comprising, and preferably consisting of, flowering tops ofInula helenium]:extraction solvent ratio by weight may be about 1:10.

[0183] According to a first embodiment, the plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process in which:- step a) is a step of maceration by mechanical stirring,- the stirring speed being 300 rpm,- the extraction solvent consisting of a mixture of water and of ethanol in a water:ethanol ratio by weight of about 70:30;- the duration of step a) being about 1 hour;- the extraction temperature being about 50°C; and- the maceration step being carried out with a [plant biomass comprising, and in particular consisting of, flowering tops ofInula helenium]:extraction solvent ratio by weight of about 1:10.

[0184] According to a second embodiment, the plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process in which:- step a) is a step of maceration by mechanical stirring,- the stirring speed being 300 rpm,- the extraction solvent consisting of a mixture of water and of ethanol in a water:ethanol ratio by weight of about 70:30;- the duration of step a) being about 1 hour;- step a) being carried out without heating; and- the maceration step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:10.

[0185] According to a third embodiment, the plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process in which:- step a) is a step of maceration by mechanical stirring,- the stirring speed being 300 rpm,- the extraction solvent consisting of a mixture of water and of ethanol in a water:ethanol ratio by weight of about 60:40;- the duration of step a) being about 1 hour;- step a) being carried out without heating; and- the maceration step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:10.

[0186] According to a fourth embodiment, the plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process in which:- step a) is a step of maceration by mechanical stirring,- the stirring speed being 300 rpm,- the extraction solvent consisting of a mixture of water and of ethanol in a water:ethanol ratio by weight of about 60:40;- the duration of step a) being about 1 hour;- the extraction temperature being about 50°C; and- the maceration step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:10.

[0187] According to a fifth embodiment, the plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process in which:- step a) is a step of maceration by mechanical stirring,- the extraction solvent consisting of propanediol;- the duration of step a) being about 2 hours;- the extraction temperature being about 80°C; and- the maceration step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:10.

[0188] According to a sixth embodiment, the plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process in which:- step a) is a step of maceration by mechanical stirring,- the extraction solvent consisting of a mixture of water and of propanediol in a water:propanediol ratio by weight of about 20:80;- the duration of step a) being about 2 hours;- the extraction temperature being about 80°C; and- the maceration step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:10.

[0189] According to a seventh embodiment, the plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process in which:- step a) is a step of maceration by mechanical stirring,- the extraction solvent consisting of a mixture of water and of propanediol in a water:propanediol ratio by weight of about 30:70;- the duration of step a) being about 2 hours;- the extraction temperature being about 80°C; and- the maceration step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:10.

[0190] According to an eighth embodiment, the plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process in which:- step a) is a step of maceration by mechanical stirring,- the extraction solvent consisting of a mixture of water and of propanediol in a water:propanediol ratio by weight of about 50:50;- the duration of step a) being about 2 hours;- the extraction temperature being about 80°C; and- the maceration step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:10.

[0191] According to a ninth embodiment, the plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process in which:- step a) is a step of maceration by mechanical stirring,- the extraction solvent consisting of acetone;- the duration of step a) being about 1 hour;- the extraction temperature being about 25°C; and- the maceration step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:10.

[0192] According to a tenth embodiment, the plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process in which:- step a) is a step of maceration by mechanical stirring,- the extraction solvent consisting of acetone;- the duration of step a) being about 1 hour;- the extraction temperature being about 50°C; and- the maceration step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:10.

[0193] According to an eleventh embodiment, the plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process in which:- step a) is a step of maceration by mechanical stirring,- the extraction solvent consisting of water;- the duration of step a) being about 1 hour;- the extraction temperature being 50°C; and- the maceration step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:10.

[0194] According to one embodiment, the extraction step of a process for obtaining a plant extract of flowering tops ofInula heleniumaccording to the invention is an extrusion step.

[0195] Preferably, the extrusion step is carried out with the aid of an extruder.

[0196] In particular, the extruder is a corotating intermeshing twin-screw extruder, such as a Clextral BC21 extruder or any other apparatus that can meet these criteria.

[0197] According to one embodiment, the extrusion step is carried out with a screw rotation speed of between 100 and 500 rpm, preferably between 150 and 450 rpm, more preferentially between 200 and 400 rpm, more preferentially still between 250 and 400 rpm, even better still between 300 and 400 rpm. In particular, the extrusion step is carried out with a screw rotation speed of about 350 rpm.

[0198] The duration of step a) of a process according to the invention, when this step is an extrusion step, preferentially lasts less than 5 minutes.

[0199] The extruder is additionally preferably constituted of two screw shafts inserted in barrels equipped with heating shells making it possible to regulate the temperature and to carry out the extraction continuously.

[0200] According to one embodiment, the extrusion step is carried out at a temperature of between 20°C and 95°C, preferably between 40°C and 95°C, more preferentially between 45°C and 85°C, more preferentially still between 50°C and 85°C. In particular, the extrusion step may be carried out at a temperature of about 80°C.

[0201] According to one embodiment, the extraction solvent used during the extrusion step comprises, and in particular consists of, at least one cosmetically acceptable, preferably polar protic, organic solvent, selected from ethanol, glycerol, propanediol, and mixtures thereof, and optionally water.

[0202] According to another embodiment, the extraction solvent used during the extrusion step is constituted of water and ethanol, of water and propanediol, of water and glycerol, or of propanediol. Preferably, the extraction solvent used in the extrusion step is constituted of propanediol or of water and propanediol.

[0203] According to one embodiment, when the extraction solvent used during the extrusion step comprises water, the cosmetically acceptable organic solvent is miscible with water.

[0204] According to one embodiment, when the extraction solvent used during the extrusion step comprises water, the water:cosmetically acceptable organic solvent(s) ratio by weight is less than or equal to 1:1. In particular, when the extraction solvent used during the extrusion step comprises water, the water:cosmetically acceptable organic solvent(s) ratio by weight is preferably between 5:95 and 1:1. For example, the water:cosmetically acceptable organic solvent(s) ratio by weight may be about 20:80.

[0205] According to one embodiment, the extraction solvent used during the extrusion step consists of water and propanediol in a water:propanediol ratio by weight of about 20:80. According to another embodiment, the extraction solvent used during the extrusion step consists of propanediol.

[0206] According to one embodiment, the extrusion step is carried out with anInula heleniumplant biomass:extraction solvent ratio by weight ranging between 1:2 and 1:5, in particular between 1:2.2 and 1:4, more particularly between 1:2.5 and 1:3. Preferably, the extrusion step is carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:2 or 1:2.9.

[0207] A draining module is advantageously arranged so as to integrate filtration screens having a cut-off threshold of about 0.8 mm, allowing the recovery of a filtrate containing the active compound(s) of interest.

[0208] The filtrate collected from the draining module is then directed to a centrifugal decanter, preferably a Lemitec model or any other model having similar characteristics. The liquid obtained at the end of this centrifugal decantation step is then transferred to a filtration system. The filtration system may advantageously be composed of one or more plate filters. Preferably, the filtration system is equipped with a double filtration stage comprising in succession a first filter with a cut-off threshold of 0.8 µm, and a second filter with a cut off threshold of 0.1 µm. The first filter may for example be of the KDS15 type. The second filter may for example be of the BECO Steril S100 type.

[0209] As indicated above, in an embodiment in which step a) is an extrusion step, the extraction duration is preferably less than 5 minutes.

[0210] According to a first embodiment, a plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process according to the invention in which:- step a) is an extrusion step,- the screw rotation speed being 350 rpm,- the extraction solvent consisting of a mixture of water and of propanediol in a water:propanediol ratio by weight of about 20:80;- step a) being carried out at an extraction temperature of 80°C; and- the extrusion step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:2.9.

[0211] According to a second embodiment, a plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process according to the invention in which:- step a) is an extrusion step,- the screw rotation speed being 350 rpm,- the extraction solvent consisting of a mixture of water and of propanediol in a water:propanediol ratio by weight of about 20:80;- step a) being carried out at an extraction temperature of 95°C; and- the extrusion step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:2.9.

[0212] According to a third embodiment, a plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process according to the invention in which:- step a) is an extrusion step,- the screw rotation speed being 350 rpm,- the extraction solvent consisting of a mixture of water and of propanediol in a water:propanediol ratio by weight of about 20:80;- step a) being carried out at an extraction temperature of 80°C; and- the extrusion step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:2.

[0213] According to a fourth embodiment, a plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process according to the invention in which:- step a) is an extrusion step,- the screw rotation speed being 350 rpm,- the extraction solvent consisting of propanediol;- step a) being carried out at an extraction temperature of 80°C; and- the extrusion step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:2.9.

[0214] According to a fifth embodiment, a plant extract of flowering tops ofInula heleniumaccording to the invention is obtained by a process according to the invention in which:- step a) is an extrusion step,- the screw rotation speed being 350 rpm,- the extraction solvent consisting of water;- step a) being carried out at an extraction temperature of between 40°C and 90°C, in particular between 45°C and 85°C, and more particularly of about 50°C; and- the extrusion step being carried out with anInula heleniumplant biomass:extraction solvent ratio by weight of about 1:2.9.

[0215] According to one embodiment, the step of a process according to the invention may be a percolation step. Percolation is a well-known method which is based on the slow and controlled passage of the extraction solvent through the plant biomass, generally disposed in the form of a fixed bed in a suitable container. Percolation enables a gradual and efficient extraction of the compounds of interest by making use of prolonged contact between the extraction solvent and the plant biomass.

[0216] According to one embodiment, step a) of a process according to the invention is implemented:- at an extraction temperature of greater than or equal to 40°C, in particular of about 50°C or of about 80°C; and- for a duration of between 10 minutes and 5 hours, in particular between 20 minutes and 1 hour;in particular, when step a) of a process according to the invention is a maceration step, the extraction solvent in particular comprising, and more particularly consisting of:- at least one cosmetically acceptable, preferably polar protic, organic solvent, more particularly selected from ethanol, propanediol, and mixtures thereof,- and optionally water,- in particular consisting of water and at least one cosmetically acceptable, preferably polar protic, organic solvent, selected from ethanol, propanediol, and mixtures thereof,in particular in a water:[ethanol and / or propanediol] ratio by weight of greater than or equal to 20:80, in particular a water:[ethanol and / or propanediol] ratio by weight of about 30:70, 40:60, 50:50, 60:40, 70:30 or 80:20.

[0217] According to one embodiment, step a) of a process according to the invention is implemented:- at an extraction temperature of between 40°C and 95°C, more preferentially between 45°C and 85°C, more preferentially still between 50°C and 85°C, and in particular being about 80°C; and- in particular for a duration of less than 5 minutes;in particular, when step a) of a process according to the invention is an extrusion step, the extraction solvent in particular comprising, and more particularly consisting of:at least one cosmetically acceptable, preferably polar protic, organic solvent, in particular selected from ethanol, glycerol, propanediol, and mixtures thereof, and optionally water, it being understood that, when the extraction solvent comprises water, the water:cosmetically acceptable organic solvent(s) ratio by weight is less than or equal to 1:1, and said cosmetically acceptable organic solvent is miscible with water;- in particular with anInula heleniumplant biomass:extraction solvent ratio by weight ranging between 1:2 and 1:5, in particular between 1:2.2 and 1:4, more particularly between 1:2.5 and 1:3, said ratio being in particular about 1:2.9.

[0218] At the end of extraction step a) as defined above, a crude plant extract ofInula helenium, in particular of flowering tops ofInula helenium, is obtained. The crudeInula heleniumplant extract thus obtained may then undergo a post-extraction treatment as defined below.

[0219] As indicated above, a process according to the invention comprises, in addition to the above-mentioned step a), at least one step b) of removing the plant biomass residues, in particular by decantation and / or filtration, said step b) being carried out after the extraction step a).

[0220] Step b) of removing the plant biomass residues has the aim of separating the plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniumfrom the extraction solvent.

[0221] According to one embodiment, step b) of a process for obtaining a plant extract of flowering tops ofInula heleniumaccording to the invention may be a decantation and / or filtration step.

[0222] Decantation is based on the natural sedimentation of solid particles suspended in liquid. This step may be carried out by simple gravity, by leaving the mixture to stand in a suitable container for a determined period of time, thus allowing the residues to settle at the bottom. The clarified liquid can then be recovered by simple withdrawal or siphoning. To accelerate the process or for more complex suspensions, it is possible to use assisted processes well-known to those skilled in the art, such as centrifugation.

[0223] In addition or as an alternative, filtration can be used to remove the plant biomass residues. This process consists in passing the liquid through a filter, such as a screen, a filtering membrane or a specific fabric, capable of retaining the solid particles. Depending on the desired fineness, different types of filters can be employed, ranging from coarse filters for prefiltration to fine-porosity membranes for advanced clarification.

[0224] According to one embodiment, step b) of a process for obtaining a plant extract of flowering tops ofInula heleniumaccording to the invention comprises at least one decantation step b’). The decantation step b’) may optionally be a centrifugal decantation step, that is to say, as indicated above, a decantation step comprising a centrifugation step at the end of which the liquid supernatant is recovered.At the end of decantation step b’), the supernatant obtained may be isolated.

[0225] According to another embodiment, step b) of a process for obtaining a plant extract of flowering tops ofInula heleniumaccording to the invention does not comprise any decantation step b’).

[0226] According to one embodiment, step b) of a process for obtaining a plant extract of flowering tops ofInula heleniumaccording to the invention comprises at least one filtration step b’’). The filtration step b’’) is carried out with at least one filter making it possible to obtain a filtrate.

[0227] According to one embodiment, the filtration step b’’) is carried out with one or more filtration steps sequentially employing one or more filters. In particular, a filtration step b’’) sequentially employs 3 filters, with cut-off thresholds that differ from one another.

[0228] According to one embodiment, the one or more filters used during the at least one filtration step b’’) are constituted of a cloth, such as a nylon cloth. According to one embodiment, the one or more filters used during the at least one filtration step b’’) correspond to one or more cellulose plate filters.

[0229] According to one embodiment, multiple filters are used during the at least one filtration step b’’), some of said filters being constituted of a cloth such as a nylon cloth and others of them being constituted of cellulose plates, the step(s) of filtration through cloth filters preceding the step(s) of filtration through cellulose plate filters.

[0230] According to one embodiment, the one or more filters used during the at least one filtration step b’’) individually have a cut-off threshold of between 0.1 microns and 500 microns. In particular, a process according to the invention comprises multiple filtration steps b’’) sequentially employing one or more filters, in particular with cut-off threshold(s) individually of between 50 and 500 microns and / or of between 0.1 and 25 microns, such as 0.2 microns.

[0231] According to a particular embodiment, step b’’) comprises a step of filtration with one or more filters having a cut-off threshold of less than or equal to 0.2 microns. Preferably, step b’’) comprises a step of filtration with one or more filters having a cut-off threshold of less than or equal to 0.2 microns when the extraction solvent comprises water.

[0232] According to another particular embodiment, step b) of a process for obtaining a plant extract of flowering tops ofInula heleniumaccording to the invention comprises one or more filtration steps b’’).

[0233] According to one embodiment, the filtrate obtained during a first filtration step b’’) is centrifuged. According to one embodiment, the filtrate obtained during a first filtration step b’’) is centrifuged and pressed, preferably pressed and then centrifuged.

[0234] The supernatant thus isolated may be employed in a second filtration step b’’). The step b) of a process for obtaining a plant extract of flowering tops ofInula heleniumaccording to the invention may thus comprise 2 filtration steps b’’).

[0235] According to one embodiment, the one or more filter(s) used during the first filtration step b’’) are constituted of a cloth, such as a nylon cloth, in particular with a cut-off threshold of 100 microns; and / or the one or more filter(s) used during the second filtration step b’’) correspond to one or more cellulose plate filters, in particular with a cut-off threshold of between 0.2 microns and 10 microns.

[0236] Preferably, the second filtration step b’’) is carried out in cascade, with one or more filters, in particular one or more cellulose plate filters, having a decreasing cut-off threshold, the cut-off threshold being sequentially between 10 microns and 0.2 microns. In particular, 3 cellulose plate filters having a decreasing cut-off threshold, of between 10 microns and 0.2 microns, may be employed in the second filtration step b’’). A sterile, liquidInula heleniumplant extract may thus be obtained.

[0237] According to one embodiment, step b) of a process for obtaining a plant extract of flowering tops ofInula heleniumaccording to the invention comprises one or more decantation steps b’) and / or one or more filtration steps b’’).

[0238] According to one embodiment, step b) of a process for obtaining a plant extract of flowering tops ofInula heleniumaccording to the invention comprises at least one decantation step b’) and / or at least one filtration step b’’), and in particular comprises at least one decantation step b’) and at least one filtration step b’’).

[0239] According to one embodiment, when both a decantation step b’) and one or more filtration steps b’’) are implemented, the decantation step b’) is carried out prior to the filtration step(s) b’’).

[0240] According to another embodiment, when step b) of a process for obtaining a plant extract of flowering tops ofInula heleniumaccording to the invention comprises a decantation step b’) and two filtration steps b’’), the decantation step b’) is implemented after a first filtration step b’’) and prior to a second filtration step b’’).

[0241] Thus, the plant extract of flowering tops ofInula heleniumaccording to the invention may be obtained by a process wherein step b) of removing the plant biomass residues comprises:- at least one step b’) of decantation, optionally centrifugal decantation, the supernatant obtained at the end of the decantation step being isolated; and / or- at least one step b’’) of filtration with at least one filter making it possible to obtain a filtrate, said filter(s) individually having a cut-off threshold of between 0.1 microns and 500 microns, in particular multiple filtration steps sequentially employing one or more filters, in particular with cut-off threshold(s) individually of between 50 and 500 microns and / or of between 0.1 and 25 microns, such as 0.2 microns.

[0242] At the end of step b) of removing the plant biomass residues as defined above, a filtrate ofInula helenium, in particular of flowering tops ofInula helenium, is obtained. TheInula heleniumplant biomass thus separated from the filtrate is removed.

[0243] At the end of step b) of removing the plant biomass residues as defined above, a step c) of total or partial evaporation of the extraction solvent may be carried out.

[0244] If the evaporation is total, a dry extract is obtained.

[0245] If there is no evaporation or if this evaporation is partial, a liquid extract is obtained.

[0246] According to one embodiment, the plant extract of flowering tops ofInula heleniumis obtained by a process according to the invention additionally comprising a step c) of total evaporation, preferably under reduced pressure, of the extraction solvent.

[0247] According to one embodiment, the plant extract of flowering tops ofInula heleniumobtained by a process according to the invention is a dry extract.

[0248] According to one embodiment, theInula heleniumdry extract comprises less than 10% by weight, preferably less than 5% by weight, preferably less than 3% by weight, preferably less than 1% by weight, preferably less than 0.5% by weight, relative to the total weight of extract, of extraction solvent. Preferably, the dry extract is free of extraction solvent.

[0249] According to one embodiment, when the extraction solvent comprises ethanol, a step c) of total evaporation of the solvent is implemented.

[0250] When step c) is a step of total evaporation of the extraction solvent, the dry extract thus obtained may optionally be ground and / or packaged, for example in a glass bottle.

[0251] According to another embodiment, the plant extract of flowering tops ofInula heleniumis obtained by a process according to the invention additionally comprising a step c) of partial evaporation of the extraction solvent.

[0252] According to one embodiment, the plant extract of flowering tops ofInula heleniumobtained by a process according to the invention is a liquid extract.

[0253] According to one embodiment, theInula heleniumliquid extract comprises a content of greater than 10% by weight, relative to the total weight of extract, of extraction solvent.

[0254] When step c) is a step of partial evaporation of the extraction solvent, the liquid extract thus obtained may optionally be packaged, for example in a glass or plastic bottle.

[0255] According to another embodiment, the plant extract ofInula helenium, in particular of flowering tops ofInula helenium, is obtained by a process according to the invention not comprising any step c) of total or partial evaporation of the extraction solvent.

[0256] Thus, the plant extract of flowing tops ofInula heleniumaccording to the invention may be obtained by a process according to the invention additionally comprising a step c), after step b), b’) and / or b’’), of total or partial removal of the residual extraction solvent present in the filtrate obtained at the end of step b), b’) and / or b’’). SaidInula heleniumplant extract obtained by the obtainment process according to the invention may be an extract in solid or liquid form.Inula helenium plant extract

[0257] The present invention also relates to anInula heleniumplant extract obtained by a process according to the invention. This extract may be in solid or liquid form.

[0258] In liquid form, the extract may result directly from the extraction process, after removal of the solid residues according to a step defined above, and optionally concentrated by total or partial evaporation of the extraction solvent. This form is particularly suitable for applications requiring high solubility or easy incorporation in liquid formulations, such as cosmetic serums, lotions or emulsions. The liquid extract may also be stabilized, for example by adding cosmetically acceptable preservatives or by adjusting the pH, in order to ensure the shelf life and efficacy thereof.

[0259] In solid form, the extract may be obtained by partial or total evaporation of the extraction solvent as mentioned above. Spray-drying or freeze-drying may also be used. These techniques make it possible to remove the residual solvent or water in order to obtain a powder or granules concentrated in compounds. This solid form offers excellent chemical stability and facilitates the storage, transport and handling of the extract. It is also advantageous for formulations requiring precise dosing or integration into powdered or solid products, or into formulations employing solvents that differ from the extraction solvent.

[0260] The present invention also relates to a solid or liquid plant extract comprising, and preferably consisting of, flowering tops ofInula helenium, characterized in that it comprises:(i) optionally fumaric acid, and / or a salt thereof, in particular in a content of between 0.05% and 3.5% by weight relative to the total weight of dry matter in the plant extract;(ii) chlorogenic acid, and / or a salt thereof, in particular in a content of between 1.5% and 4% by weight relative to the total weight of dry matter in the plant extract;(iii) cryptochlorogenic acid, and / or a salt thereof, in particular in a content of between 0.25% and 1.5% by weight relative to the total weight of dry matter in the plant extract;(iv) neochlorogenic acid, and / or a salt thereof, in particular in a content of between 0.01% and 0.7% by weight relative to the total weight of dry matter in the plant extract;(v) 1,5-dicaffeoylquinic acid, and / or a salt thereof, in particular in a content of between 1.5% and 5% by weight relative to the total weight of dry matter in the plant extract;(vi) isochlorogenic acid B, and / or a salt thereof, in particular in a content of between 0.1% and 0.5% by weight relative to the total weight of dry matter in the plant extract;(vii) isochlorogenic acid A, and / or a salt thereof, in particular in a content of between 0.4% and 5% by weight relative to the total weight of dry matter in the plant extract; and(viii) 4,5-dicaffeoylquinic acid, and / or a salt thereof, in particular in a content of between 0.1% and 6% by weight relative to the total weight of dry matter in the plant extract.

[0261] The solid or liquid plant extract further comprises Costunolide; 2 alpha hydroxy alantolactone; 4,5-epoxy-10,14-dihydroinuviscolide; Dehydroivaxilin; 10-hydroxy-14H inuviscolide; 3-O-methylquercetin; Kaempferol 3-O-glucoside; Quercetin 3-O-glucoside; Hyperoside (quercetin 3-D-galactoside); Isorhamnetin 3-O-glucoside; 1,4-dicaffeoylquinic acid; 3,5-dicaffeoylquinic acid; Atractyligenin 2-O-glucoside; Kaempferol rutinoside; and / or 3,4,5-tricaffeoylquinic acid.

[0262] Such an extract may in addition optionally comprise:(ix) at least one polyphenol, and / or a salt thereof, in particular in a content of between 10% and 20% by weight relative to the total weight of dry matter in the plant extract, wherein the at least one polyphenol is different from chlorogenic acid; cryptochlorogenic acid; neochlorogenic acid; 1,5-dicaffeoylquinic acid; isochlorogenic acid B; isochlorogenic acid A; 4,5-dicaffeoylquinic acid; 1,4-dicaffeoylquinic acid; 3,5-dicaffeoylquinic acid; 3,4,5-tricaffeoylquinic acid; 3-O-methylquercetin; Kaempferol 3-O-glucoside; Quercetin 3-O-glucoside; Hyperoside (quercetin 3-D-galactoside); Isorhamnetin 3-O-glucoside and Kaempferol rutinoside; and / or(x) at least one (poly)amino acid; and / or(xi) at least one (poly)saccharide.

[0263] Such an extract may in addition comprise:(xii) optionally at least one sesquiterpene lactone and / or glycosylated derivatives thereof, more particularly at least alantolactone and / or isoalantolactone and / or dehydrocostus lactone and / or isomers thereof, and / or glycosylated derivatives thereof, the total content of sesquiterpene lactone(s) and / or glycosylated derivatives thereof being in particular less than 1%, more particularly less than 0.1%, by weight relative to the total weight of dry matter in the plant extract, in particular less than 100 ppm; and / or(xiii) optionally at least one caffeic acid, and / or a salt thereof, the total content of caffeic acid being in particular less than 1%, more particularly less than 0.1%, by weight relative to the total weight of dry matter in the plant extract, in particular less than 100 ppm; and / or(xiv) optionally at least quercetin, the total content of quercetin being in particular less than 1%, more particularly less than 0.1%, by weight relative to the total weight of dry matter in the plant extract, in particular less than 100 ppm.Cosmetic composition

[0264] According to a first aspect, a composition according to the invention is preferentially cosmetic, non-therapeutic, optionally dermatological, and comprises at least oneInula heleniumplant extract according to the invention.

[0265] TheInula heleniumplant extract according to the invention may be present in the composition in a concentration of between 0.001% and 5% by weight of dry matter in the plant extract, preferably between 0.005% and 2% by weight of dry matter in the plant extract, even better still between 0.01% and 1% by weight of dry matter in the plant extract, relative to the total weight of the composition.

[0266] In a composition according to the invention, theInula heleniumplant extract according to the invention is comprised within a physiologically acceptable medium, i.e. a medium that is suitable for administering a composition topically, i.e. a medium that is compatible with keratin materials, and more particularly with the skin.

[0267] A composition according to the invention may comprise an aqueous phase and / or fatty phase.Aqueous phase

[0268] An aqueous phase of a composition used according to the invention may comprise water and optionally a water-soluble organic solvent and is, preferably, single-phase.

[0269] More particularly, said physiologically acceptable medium may comprise water and / or one or more cosmetically acceptable organic solvent(s), in particular one or more water-miscible polar protic organic solvent(s).

[0270] According to a preferred embodiment, a composition according to the present invention comprises a water content of between 10% and 98% by weight, preferably between 25% and 90% by weight, and more preferentially between 35% and 85%, relative to the total weight of the composition.

[0271] According to the present invention, the term “water-soluble organic solvent” is understood to denote a compound that is liquid at ambient temperature and miscible with water (miscibility with water of greater than 50% by weight at 25°C and atmospheric pressure).

[0272] The water-soluble solvents that can be used in a composition of the invention may be volatile.

[0273] Among the water-soluble solvents that can be used in a composition according to the invention, mention may be made most particularly of lower monoalcohols having from 1 to 5 carbon atoms, such as ethanol and isopropanol, polyols and also alkylene carbonates.

[0274] According to an embodiment variant, the aqueous phase of a composition according to the invention may comprise at least one C2-C32polyol.

[0275] For the purposes of the present invention, the term “polyol” is understood to mean any organic molecule comprising at least two free hydroxyl (OH) groups.

[0276] A polyol that is suitable for use in the invention may be a compound of alkyl type with a linear, branched or cyclic, saturated or unsaturated hydrocarbon chain, bearing at least two –OH functions on the alkyl chain. Preferably, a polyol that may be used in the composition according to the invention is a compound of the linear alkyl type bearing on the alkyl chain at least two –OH functions, preferably from 2 to 6 hydroxyl –OH groups, more preferentially 2 or 3 hydroxyl groups.

[0277] The polyol(s) advantageously suitable for the formulation of the cosmetic compositions according to the present invention is (are) those having in particular from 2 to 16 carbon atoms, preferably 3 to 10 carbon atoms and more preferentially from 3 to 8 carbon atoms.

[0278] The polyol(s) that may be used according to the present invention is (are) selected from linear polyols having from 3 to 8 carbon atoms; mention may be made in particular of:- diols, such as propylene glycol, butylene glycol, pentylene glycol; and- triols, such as glycerol (glycerine),and mixtures thereof.

[0279] According to a particularly preferred embodiment, the polyol is selected from triols such as glycerol.

[0280] The aqueous phase of a composition according to the invention may also comprise any water-soluble or water-dispersible compound that is compatible with an aqueous phase, such as stabilizers, gelling agents, film-forming polymers, thickeners, surfactants, and mixtures thereof.Fatty phase

[0281] As mentioned above, a composition according to the invention may comprise at least one fatty phase.

[0282] For the purposes of the invention, the term “fatty phase” is understood to mean all of the lipophilic components forming part of a formulation, whether they be liquid, semi-solid or solid at ambient temperature. This includes in particular oils, butters, waxes, and also fatty acids, lipid esters and other fatty substances, used for the formulation of the compositions of the invention.

[0283] In particular, a composition according to the invention may comprise from 5% to 95% by weight and preferably from 10% to 80% by weight of fatty phase, relative to the total weight of the composition.

[0284] The fatty phase of a composition according to the invention may in particular comprise at least one oil, in particular a cosmetic oil.Oils

[0285] The term “oil” is understood to mean a water-immiscible non-aqueous compound that is liquid at ambient temperature (20°C) and atmospheric pressure (760 mmHg).

[0286] A fatty phase that is suitable for preparing the compositions, in particular cosmetic compositions, according to the invention may comprise hydrocarbon oils, silicone oils, fluoro oils or non-fluoro oils, or mixtures thereof.

[0287] The oils may be volatile or non-volatile.

[0288] For the purposes of the present invention, the term “hydrocarbon oil” is understood to mean an oil containing mainly hydrogen and carbon atoms.

[0289] The term “silicone oil” is understood to mean an oil comprising at least one silicon atom and in particular at least one Si-O group.

[0290] The term “fluorooil” is understood to mean an oil comprising at least one fluorine atom.

[0291] The oils may optionally comprise oxygen, nitrogen, sulfur and / or phosphorus atoms, for example in the form of hydroxyl or acid radicals.Volatile oils

[0292] For the purposes of the invention, the term “volatile oil” is understood to mean any oil that is capable of evaporating on contact with the skin in less than one hour, at ambient temperature and atmospheric pressure. The volatile oil is a volatile cosmetic compound, which is liquid at ambient temperature, having in particular a non-zero vapour pressure, at ambient temperature and atmospheric pressure, in particular having a vapour pressure ranging from 0.13 Pa to 40 000 Pa (10-3to 300 mmHg), in particular ranging from 1.3 Pa to 13 000 Pa (0.01 to 100 mmHg) and more particularly ranging from 1.3 Pa to 1300 Pa (0.01 to 10 mmHg).

[0293] The volatile oils may be hydrocarbon oils or silicone oils.

[0294] Among the volatile hydrocarbon oils having from 8 to 16 carbon atoms, mention may in particular be made of branched C8-C16alkanes such as C8-C16isoalkanes (also known as isoparaffins), isododecane, isodecane, isohexadecane and, for example, the oils sold under the trade names Isopar or Permethyl, branched C8-C16esters such as isohexyl neopentanoate, and mixtures thereof.

[0295] Mention may also be made of volatile linear alkanes comprising from 8 to 16 carbon atoms, in particular from 10 to 15 carbon atoms, and more particularly from 11 to 13 carbon atoms, for instance n-dodecane (C12) and n-tetradecane (C14) sold by Sasol under the respective references Parafol 12-97 and Parafol 14-97, and also mixtures thereof, the undecane-tridecane mixture, the mixtures of n-undecane (C11) and of n-tridecane (C13) obtained in examples 1 and 2 of patent application WO 2008 / 155059 from the company Cognis, and mixtures thereof.

[0296] Volatile silicone oils that may be mentioned include linear volatile silicone oils such as hexamethyldisiloxane, octamethyltrisiloxane, decamethyltetrasiloxane, tetradecamethylhexasiloxane, hexadecamethylheptasiloxane and dodecamethylpentasiloxane.

[0297] Volatile cyclic silicone oils that may be mentioned include hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, cyclohexasiloxane and dodecamethylcyclohexasiloxane, and in particular cyclohexasiloxane.

[0298] Use may also be made of volatile fluoro oils, such as nonafluoromethoxybutane, nonafluoromethoxybutane, decafluoropentane, tetradecafluorohexane, dodecafluoropentane, and mixtures thereof.Non-volatile oils

[0299] The term “non-volatile” is understood to refer to an oil of which the vapour pressure at ambient temperature and atmospheric pressure is non-zero and is less than 10-3 mmHg (0.13 Pa).

[0300] The non-volatile oils may, in particular, be selected from non-volatile hydrocarbon, fluoro and / or silicone oils.

[0301] Non-volatile hydrocarbon oils that may in particular be mentioned include:- linear or branched hydrocarbons of mineral or synthetic origin, such as petroleum jelly, polydecenes, hydrogenated polyisobutene, such as Parleam, and squalane, and mixtures thereof,- non-volatile alkanes, preferably with a viscosity of less than 20 mPa.s at 20°C measured with a Rheomat RM100® viscometer from Lamy Rheology. The term “non-volatile alkane” is understood to mean a hydrocarbon cosmetic oil which is liquid at ambient temperature, having in particular a vapour pressure at 20°C of less than 0.01 kPa, according to the definition of a Volatile Organic Compound (VOC) of article 2 of European Council Directive 1999 / 13 / EC of 11 March, 1992: “Any organic compound having at 293.15 K a vapour pressure of 0.01 kPa or more”. In particular, the non-volatile alkanes comprise from 10 to 30 carbon atoms, in particular from 12 to 26 carbon atoms, and more particularly from 15 to 19 carbon atoms, and preferably a mixture of alkanes containing from 15 to 19 carbon atoms, for example the products sold under the references Emogreen L19 and Emosmart L19 from SEPPIC,- hydrocarbon oils of plant origin, such as glyceride triesters, which are generally fatty acid triesters of glycerol, the fatty acids of which may have varied chain lengths from 4 to 24 carbon atoms, it being possible for these chains to be saturated or unsaturated and linear or branched; these oils are in particular wheatgerm oil, sunflower oil, grape seed oil, sesame oil, maize oil, apricot oil, castor oil, shea oil, avocado oil, olive oil, soybean oil, sweet almond oil, palm oil, rapeseed oil, cottonseed oil, hazelnut oil, macadamia oil, jojoba oil, alfalfa oil, poppy oil, pumpkin oil, sesame oil, marrow oil, rapeseed oil, blackcurrant oil, evening primrose oil, millet oil, barley oil, quinoa oil, rye oil, safflower oil, candlenut oil, passionflower oil and musk rose oil; or else caprylic / capric acid triglycerides, such as those sold by the company Stéarinerie Dubois or those sold under the names Miglyol 810, 812 and 818 by the company Dynamit Nobel,- synthetic ethers having from 10 to 40 carbon atoms, such as dicapryl ether,- synthetic esters, such as the oils of formula R1COOR2, in which R1represents a residue of a linear or branched fatty acid comprising from 1 to 40 carbon atoms and R2represents an, in particular branched, hydrocarbon chain containing from 1 to 40 carbon atoms, provided that R1+ R2is greater than or equal to 10, such as for example PurCellin oil (cetostearyl octanoate), isopropyl myristate, isopropyl palmitate, alkyl benzoate having between 12 and 15 carbon atoms, such as the product sold under the trade name Finsolv TN or Witconol TN by the company Witco or Tegosoft TN by the company Evonik Goldschmidt, 2-ethylphenyl benzoate such as the commercial product sold under the name X-Tend 226 by the company ISP, isopropyl lanolate, hexyl laurate, diisopropyl adipate, isononyl isononanoate, oleyl erucate, 2-ethylhexyl palmitate, isostearyl isostearate, diisopropyl sebacate such as the product sold under the name Dub Dis by the company Stéarinerie Dubois, octanoates, decanoates or ricinoleates of alcohols or of polyalcohols such as propylene glycol dioctanoate; hydroxylated esters such as isostearyl lactate, diisostearyl malate; pentaerythritol esters; citrates, such as the ester of C3-C22tricarboxylic acid and of C1-C6alcohols having the INCI name Triethyl Citrate, for example that sold under the name Citrofol AI Extra by the company Jungbunzlauer; tartrates such as linear dialkyl tartrates having 12 or 13 carbon atoms, for example those sold under the name Cosmacol ETI by the company Enichem Augusta Industriale and also linear dialkyl tartrates having between 14 and 15 carbon atoms, for example, those sold under the name Cosmacol ETL by the same company, and acetates,- fatty amides, such as isopropyl N-lauroyl sarcosinate, for example the product sold under the trade name Eldew SL205 from Ajinomoto,- polyol esters and pentaerythritol esters, such as dipentaerythrityl tetrahydroxystearate / tetraisostearate,- fatty alcohols that are liquid at ambient temperature, with a branched and / or unsaturated carbon chain having from 12 to 26 carbon atoms, such as octyldodecanol, isostearyl alcohol, oleyl alcohol, 2-hexyldecanol, 2-butyloctanol, 2-undecylpentadecanol,- C12-C22higher fatty acids, such as oleic acid, linoleic acid, linolenic acid, and mixtures thereof,- carbonates, such as dicaprylyl carbonate, for example the product sold under the name Cetiol CC by the company Cognis,- non-phenyl silicone oils, for instance caprylyl methicone, and- phenyl silicone oils, for instance phenyl trimethicones, phenyl dimethicones, phenyltrimethylsiloxydiphenylsiloxanes, diphenyl dimethicones, diphenylmethyldiphenyltrisiloxanes and 2-phenylethyl trimethylsiloxysilicates, dimethicones or phenyl trimethicone with a viscosity of less than or equal to 100 cSt, and trimethylpentaphenyltrisiloxane, and mixtures thereof,and also mixtures of these various oils.Additional compound(s)

[0302] A composition according to the invention may also comprise one or more additional compounds. This or these additional compound(s) are different from an extract according to the invention.

[0303] Needless to say, a person skilled in the art will take care to select this / these additional compound(s) such that the advantageous properties of an extract according to the invention are not, or are not substantially, adversely affected.

[0304] As additional compounds, mention may for example be made of moisturizers; depigmenting agents, desquamating agents, anti-wrinkle agents, antioxidants, mattifying agents; cicatrizing agents; preservatives such as antibacterial agents; UV-screening agents; emollients; sequestrants; fillers; fragrances; film-forming agents; thickeners; surfactants; colorants, and mixtures thereof.

[0305] Preferably, a composition according to the invention comprises from 0.01% to 20% by total weight of at least one additional compound, preferentially from 0.05% to 15% by weight, and preferentially from 0.1% to 10% by weight, of at least one additional compound relative to the total weight of the composition.

[0306] A composition according to the invention may be in any presentation form normally used in the cosmetics field, in particular in the cosmetics field of skin care.

[0307] It may in particular be in the form of an aqueous or aqueous-alcoholic solution, which may be gelled, a dispersion of the lotion type, which may be a two-phase dispersion, an oil-in-water or water-in-oil emulsion or a multiple emulsion, a gel, in particular an aqueous gel, or a dispersion of oils in an aqueous phase, in particular using spherules, it being possible for these spherules to be polymeric particles or, better still, lipid vesicles of ionic and / or nonionic type. In particular, a composition according to the invention may be in the form of a gel, especially an aqueous gel. It may also be an anhydrous composition. The term “anhydrous composition” is understood to mean a composition containing less than 10% by weight of water, in particular less than 5% by weight of water, more particularly less than 2% by weight of water, or even less than 0.5% water, and especially free of water, the water not being added during the preparation of the composition but corresponding to the residual water provided by the mixed ingredients. The composition may be of more or less fluid liquid consistency.

[0308] A composition according to the invention is in particular suitable for topical administration.

[0309] Thus, a composition according to the invention may comprise all the constituents usually employed in the envisaged topical application and administration.

[0310] A composition according to the invention may advantageously be in the form of an emulsion, especially obtained by dispersion of an aqueous phase in a fatty phase (W / O) or of a fatty phase in an aqueous phase (O / W), of liquid or semi-liquid consistency of the milk type, or of soft consistency, or alternatively of a multiple emulsion (W / O / W or O / W / O). These compositions are prepared according to the usual known methods.

[0311] More particularly, a composition according to the invention may be intended for topical application and in particular may be in the form of an emulsion, in particular an oil-in-water emulsion. In particular, such an emulsion is not intended to be rinsed off after application.

[0312] A composition according to the invention is more particularly intended to be applied to skin.

[0313] In particular, the skin is the skin of the face, scalp, neckline, neck, arms or forearms, or even more preferably the skin of the face (in particular of the forehead, nose, cheeks and chin), neckline and neck.

[0314] The composition according to the invention may alternatively be in the form of a face and / or body care or makeup product, and may be packaged, for example, in the form of a cream in a jar or a fluid in a tube or a pump bottle or a dropper bottle.

[0315] A composition according to the invention can be manufactured by any known process generally used in the cosmetics field.

[0316] The ingredients may be mixed before shaping, in the order and under conditions readily determined by a person skilled in the art.

[0317] According to a particular mode of the invention, other agents intended to enhance the appearance and / or texture of the skin may also be added to the composition according to the invention.

[0318] In particular, a composition used according to the invention, which is especially topical, is:

[0319] (i) liquid, preferably selected from creams, emulsions, lotions, dispersions, solutions, gels, balms and serums; or

[0320] (ii) solid, preferably selected from masks and sticks.

[0321] It is a matter of routine operation for those skilled in the art to adjust the nature and the amount of the cosmetic agents and / or additives present in the compositions in accordance with the invention such that the desired cosmetic properties, properties of comfort on application and stability properties thereof are not affected thereby.

[0322] A composition of the invention may be obtained via any preparation process known to those skilled in the art.

[0323] According to another aspect, a cosmetic composition according to the invention is a cosmetic composition intended for oral administration, particularly in the form of a food supplement. Said composition comprises at least one plant extract ofInula heleniumaccording to the invention.

[0324] TheInula heleniumplant extract according to the invention may be present in the composition :- in a concentration of between 0.1% and 10% by weight of dry matter in the plant extract relative to the total weight of the composition, in particular when the plant extract is obtained by a process according to the invention, wherein the extraction step a) is an extrusion step as described herein;- preferably in a concentration of between 0.1% and 2.5% by weight of dry matter in the plant extract relative to the total weight of the composition, in particular when the plant extract is obtained by a process according to the invention, wherein the extraction step a) is a maceration step as described herein.

[0325] In a composition according to the invention, theInula heleniumplant extract according to the invention is included in a physiologically acceptable medium, i.e. a medium suitable for the oral administration of the composition.

[0326] A composition according to the invention may be in any presentation form normally used in the cosmetic field, particularly in the field of food supplements. A galenic form suitable for oral administration notably includes a drinkable solution, a syrup, a tablet, a coated tablet, a capsule, particularly a soft capsule, gummies, a gel, a dry or liquid emulsion, a powder, including a compacted powder or a powder to be diluted, or a drinkable ampoule. It may also be in the form of an enriched food product, such as a biscuit, a nutritional bar, or any other solid or liquid preparation intended for ingestion. The powders can notably be diluted in water, soda, dairy products or soy derivatives, or incorporated into bars or biscuits.According to one embodiment, the composition is in the form of a food supplement, and notably in the form of soft capsules or capsules, coated capsules, coated tablets, syrup, gummies, gels, dry or liquid emulsions, tablets, powders to be diluted or drinkable ampoules, or an enriched food product.

[0327] A composition according to the invention may also include at least one edible excipient. This or these excipient(s) are different from an extract according to the invention. Naturally, a person skilled in the art will ensure that such excipient(s) are chosen such that the advantageous properties of an extract according to the invention are not, or are not substantially, adversely affected.In this regard, formulation agents, adjuvants, and excipients intended for oral compositions, particularly food supplements, are well known to those skilled in the art. Non-exhaustively and purely illustratively, lubricants such as magnesium stearate, instant solubilization agents, gelling agents, bulking agent, thickeners, humectants, fatty and / or aqueous components, preservatives, as well as texture, flavor, and / or coating agents, antioxidants and common food colorants can be cited.According to one embodiment, the composition includes at least one edible excipient chosen from colorants, sweeteners, bulking agents, binders, and preservatives.Preferably, a composition according to the invention comprises from 0.01% to 99.9% by total weight of at least one excipient, preferably from 0.05% to 90% by weight, and preferably from 0.1% to 80% by weight of at least one excipient relative to the total weight of the composition. The ingredients can be mixed before shaping them, in the order and under conditions easily determined by those skilled in the art.

[0328] Thus, an oral cosmetic composition according to the invention may include all the constituents usually employed in the intended oral application and administration and may be obtained by any preparation process known to those skilled in the art.Use and cosmetic treatment process

[0329] The present invention also relates to the use of a plant extract according to the invention or of a composition according to the invention, administered by oral or topical route, for preventing and / or treating a chronic inflammatory skin disorder, in particular a pigmentary disorder. The pigmentary disorder is in particular (i) a pigmentary spot, in particular an actinic lentigo, or (ii) post-inflammatory hyperpigmentation, in particular associated with a scar or an unaesthetic disorder consecutive to an inflammatory skin manifestation, in particular a scar or an acne mark, a scar or a rosacea mark or (iii) melasma.

[0330] The present invention also relates to a process for the cosmetic, in particular non-therapeutic, treatment of a keratin material, comprising at least one step of applying to said keratin material anInula heleniumplant extract according to the invention or a composition according to the invention.

[0331] The skin under consideration according to the present invention is preferentially human skin.

[0332] The keratin material is preferentially the skin, the lips, the eyelashes and / or the hair, in particular the skin and / or the lips, and in particular is (i) the skin of the body, including the skin of the scalp, and / or (ii) the skin of the face, and more particularly is the skin of the face.

[0333] A non-therapeutic cosmetic process of the invention is in particular characterized in that it is intended to prevent and / or treat a chronic inflammatory disorder, in particular a pigmentary disorder. The pigmentary disorder is in particular (i) a pigmentary spot, in particular an actinic lentigo, or (ii) post-inflammatory hyperpigmentation, in particular a scar or an unaesthetic disorder consecutive to an inflammatory skin manifestation, in particular a scar or an acne mark, a scar or a rosacea mark or (iii) melasma.

[0334] A use and a process according to the invention are preferentially implemented topically or orally.

[0335] The topical administration consists of the external application to a keratin material, in particular to the skin, more particularly to the skin of the face, of anInula heleniumextract according to the invention, or of a cosmetic composition according to the invention, according to the usual techniques of use in this field.

[0336] By way of illustration, the process or the use according to the invention may be implemented by topical application, for example daily, of such anInula heleniumplant extract or of such a composition.

[0337] The application may be repeated for example once or twice daily over a day or more, and generally over an extended period of at least 3 days, at least 4 weeks, or even 4 to 15 weeks, with, where appropriate, one or more periods of stoppage.

[0338] According to one embodiment, the application is daily (once a day) and generally over an extended period of at least 3 days, at least 4 weeks, or even 4 to 15 weeks, with, where appropriate, one or more periods of stoppage.

[0339] According to one embodiment, the cosmetic treatment process according to the invention may comprise a single application.

[0340] Oral administration consists of the ingestion of anInula heleniumplant extract according to the invention, or of a composition according to the invention, by the oral route, according to the usual techniques of use in this field.

[0341] Administration may be repeated, for example once or more per day, over a day or more, and generally over an extended period of at least 3 days, at least 4 weeks, or even 4 to 15 weeks, with, where appropriate, one or more periods of stoppage.

[0342] According to one embodiment, the administration is daily (at least one intake per day), either continuously or sequentially, over a duration of at least 3 days, at least 4 weeks, or even 4 to 15 weeks.

[0343] According to another embodiment, the method according to the invention may comprise a single oral administration.

[0344] The examples that follow illustrate the present invention without limiting the scope thereof.ExamplesSynthesis examples

[0345] Example 1:Inula heleniumextract no. 1 obtained by maceration after total evaporation of the solvents

[0346] In a 2-litre jacketed reactor, on top of which are mounted a condenser and a 2-armed stirring blade connected to a motor, are introduced:- 120 g of driedInula heleniumplant biomass, consisting of flowering tops dried and then ground on a 2 mm screen, and- 1.2 kg of extraction solvent consisting of a mixture of water and of ethanol in a water:ethanol ratio by weight of 70:30.

[0347] The mixture of driedInula heleniumplant biomass and of extraction solvent is heated to 50°C with the aid of a thermo-cryostat and stirred at 300 rpm for 1 hour. The mixture is then cooled to 20°C and then filtered through a 100-micron nylon cloth. The filtrate thus obtained is centrifuged. The supernatant is isolated and then subjected to a cascade of filtrations through cellulose plate filters with a cut-off threshold ranging from 10 µm to 0.2 µm. The sterile liquid extract, amber-brown in colour, is then evaporated to dryness under reduced pressure.A dry extract in the form of a dark brown powder is finally obtained (extract no. 1).

[0348] Example 2:Inula heleniumextract no. 2 obtained by maceration without heating and after total evaporation of the solvents

[0349] In a 2-litre jacketed reactor, on top of which are mounted a condenser and a 2-armed stirring blade connected to a motor, are introduced:- 120 g of driedInula heleniumplant biomass, consisting of flowering tops dried and then ground on a 2 mm screen, and- 1.2 kg of extraction solvent consisting of a mixture of water and of ethanol in a water:ethanol ratio by weight of 70:30.

[0350] The mixture of driedInula heleniumplant biomass and of extraction solvent is stirred at 300 rpm for 1 hour without heating. The mixture is then filtered through a 100-micron nylon cloth. The filtrate thus obtained is then centrifuged and the supernatant isolated. The latter is subjected to a cascade of filtrations through cellulose plate filters with a cut-off threshold ranging from 10 µm to 0.2 µm. The sterile liquid extract, amber-brown in colour, is then evaporated to dryness under reduced pressure.A dry extract in the form of a dark brown powder is thus obtained (extract no. 2).

[0351] Example 3:Inula heleniumextract no. 3 obtained by maceration without heating and after total evaporation of the solvents

[0352] In a 2-litre jacketed reactor, on top of which are mounted a condenser and a 2-armed stirring blade connected to a motor, are introduced:- 120 g of driedInula heleniumplant biomass, consisting of flowering tops dried and then ground on a 2 mm screen, and- 1.2 kg of extraction solvent consisting of a mixture of water and of ethanol in a water:ethanol ratio by weight of 60:40.

[0353] The mixture of driedInula heleniumplant biomass and of extraction solvent is stirred at 300 rpm for 1 hour without heating. The mixture is then filtered through a 100-micron nylon cloth. The filtrate thus obtained is then centrifuged and the supernatant isolated. The latter is subjected to a cascade of filtrations through cellulose plate filters with a cut-off threshold ranging from 10 µm to 0.2 µm. The sterile liquid extract, amber-brown in colour, is then evaporated to dryness under reduced pressure.A dry extract in the form of a dark brown powder is thus obtained (extract no. 3).

[0354] Example 4:Inula heleniumextract no. 4 obtained by maceration after total evaporation of the solvents

[0355] In a 2-litre jacketed reactor, on top of which are mounted a condenser and a 2-armed stirring blade connected to a motor, are introduced:- 120 g of driedInula heleniumplant biomass, consisting of flowering tops dried and then ground on a 2 mm screen, and- 1.2 kg of extraction solvent consisting of a mixture of water and of ethanol in a water:ethanol ratio by weight of 60:40.

[0356] The mixture of driedInula heleniumplant biomass and of extraction solvent is heated to 50°C with the aid of a thermo-cryostat and stirred at 300 rpm for 1 hour. The mixture is then cooled to 20°C and then filtered through a 100-micron nylon cloth. The filtrate thus obtained is centrifuged. The supernatant is isolated and then subjected to a cascade of filtrations through cellulose plate filters with a cut-off threshold ranging from 10 µm to 0.2 µm. The sterile liquid extract, amber-brown in colour, is then evaporated to dryness under reduced pressure.A dry extract in the form of a dark brown powder is finally obtained (extract no. 4).

[0357] Example 5:Inula heleniumliquid extract no. 5 obtained by maceration

[0358] In a 1-litre reactor, on top of which is mounted a condenser, are introduced:- 500 g of extraction solvent, consisting of 1,3-propanediol, and then- under mechanical stirring with the aid of an impeller, 50 g of driedInula heleniumplant biomass, consisting of flowering tops dried and then ground on a 2 mm screen.

[0359] The mixture of driedInula heleniumplant biomass and of extraction solvent is heated at 80°C for 2 hours. The mixture is then cooled to 25°C and then filtered through a 100-micron nylon cloth and pressed. The crude extract obtained is centrifuged. The supernatant, once isolated, is subjected to a cascade of filtrations through 3 cellulose plate filters with a cut-off threshold ranging from 10 µm to 0.2 µm.A sterile liquid extract, brown in colour, is thus obtained (extract no. 5).

[0360] Example 6:Inula heleniumliquid extract no. 6 obtained by maceration

[0361] In a 1-litre reactor, on top of which is mounted a condenser, are introduced:- 500 g of extraction solvent consisting of a mixture of water and of 1,3-propanediol in a water:1,3-propanediol ratio by weight of 20:80, and then- under mechanical stirring with the aid of an impeller, 50 g of driedInula heleniumplant biomass, consisting of flowering tops dried and then ground on a 2 mm screen.

[0362] The mixture of driedInula heleniumplant biomass and of extraction solvent is heated at 80°C for 2 hours. The mixture is then cooled to 25°C and then filtered through a 100-micron nylon cloth and pressed. The crude extract obtained is centrifuged. The supernatant, once isolated, is subjected to a cascade of filtrations through 3 cellulose plate filters with a cut-off threshold ranging from 10 µm to 0.2 µm.A sterile liquid extract, brown in colour, is thus obtained (extract no. 6).

[0363] Example 7:Inula heleniumliquid extract no. 7 obtained by maceration

[0364] In a 1-litre reactor, on top of which is mounted a condenser, are introduced:- 500 g of extraction solvent consisting of a mixture of water and of 1,3-propanediol in a water:1,3-propanediol ratio by weight of 30:70, and then- under mechanical stirring with the aid of an impeller, 50 g of driedInula heleniumplant biomass, consisting of flowering tops dried and then ground on a 2 mm screen.

[0365] The mixture of driedInula heleniumplant biomass and of extraction solvent is heated at 80°C for 2 hours. The mixture is then cooled to 25°C and then filtered through a 100-micron nylon cloth and pressed. The crude extract obtained is centrifuged. The supernatant, once isolated, is subjected to a cascade of filtrations through 3 cellulose plate filters with a cut-off threshold ranging from 10 µm to 0.2 µm.A sterile liquid extract, brown in colour, is thus obtained (extract no. 7).

[0366] Example 8:Inula heleniumliquid extract no. 8 obtained by maceration

[0367] In a 1-litre reactor, on top of which is mounted a condenser, are introduced:- 500 g of extraction solvent consisting of a mixture of water and of 1,3-propanediol in a water:1,3-propanediol ratio by weight of 50:50, and then- under mechanical stirring with the aid of an impeller, 50 g of driedInula heleniumplant biomass, consisting of flowering tops dried and then ground on a 2 mm screen.

[0368] The mixture of driedInula heleniumplant biomass and of extraction solvent is heated at 80°C for 2 hours. The mixture is then cooled to 25°C and then filtered through a 100-micron nylon cloth and pressed. The crude extract obtained is centrifuged. The supernatant, once isolated, is subjected to a cascade of filtrations through 3 cellulose plate filters with a cut-off threshold ranging from 10 µm to 0.2 µm.A sterile liquid extract, brown in colour, is thus obtained (extract no. 8).

[0369] Example 9: Characterization of theInula heleniumdry extracts obtained by maceration according to Examples 1 to 4

[0370] TheInula heleniumdry extracts nos. 1 to 4, obtained according to the processes described in Examples 1 to 4, are analysed by ultra-performance liquid chromatography (UPLC) under the following conditions:Equipment: ACQUITY UPLC WatersColumn: ACQUITY BEH Shield RP18 (Waters, 100 x 2.1 mm, 1.8 μm)Column temperature: 35°CEluents:A: Water + 0.1% formic acidB: Acetonitrile + 0.1% formic acidFlow rate: 0.6 mL / min for extract no. 1 and 0.5 mL / min for extracts no. 2 to no. 4Injection volume: 2 μL (sample temperature: 10°C)PDA detection: 190 - 700 nm

[0371] The extracts are dissolved at 0.5% in a mixture of methanol and of water in a methanol:water ratio of 50:50 (v / v).

[0372] t (minutes)A (%)B (%)09911.180205.266347.001007.501007.799110991Start of the gradient at injection

[0373] Table 1 describes the elution gradient programme used during the UPLC analysis of Example 9.

[0374] Results:

[0375] The chromatograms of the 4Inula heleniumdry extracts analysed are similar. The same major compounds are found, namely:- fumaric acid (C4H4O4, M = 115 g / mol),- chlorogenic acid (3-CQA, C16H18O9, M = 354 g / mol),- isochlorogenic acid A (3,5-dicaffeoylquinic acid, C25H24O12, M = 516.45 g / mol),- 1,5-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol), and- 4,5-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol).

[0376] Extract no. 1, obtained according to Example 1 by aqueous-alcoholic maceration at 30% for 1 h at 50°C also comprises, in lesser amounts:- neochlorogenic acid (5-CQA, C16H18O9, M = 354 g / mol),- cryptochlorogenic acid (4-CQA, C16H18O9, M = 354 g / mol),- 1,3-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol), and- isochlorogenic acid B (3,4-dicaffeoylquinic acid, C25H24O12, M = 516.45 g / mol).

[0377] Extract no. 1, obtained according to Example 1 by aqueous-alcoholic maceration at 30% for 1 h at 50°C comprises, as percentage of dry extract:

[0378] - 2.48% fumaric acid (C4H4O4, M = 115 g / mol),- 2.36% chlorogenic acid (3-CQA, C16H18O9, M = 354 g / mol),- 1.14% isochlorogenic acid A (3,5-dicaffeoylquinic acid, C25H24O12, M = 516.45 g / mol),- 2.30% 1,5-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol),- 4.5% 4,5-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol),- 0.08% neochlorogenic acid (5-CQA, C16H18O9, M = 354 g / mol),- 0.04% cryptochlorogenic acid (4-CQA, C16H18O9, M = 354 g / mol),- 0.03% 1,3-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol), and- 0.13% isochlorogenic acid B (3,4-dicaffeoylquinic acid, C25H24O12, M = 516.45 g / mol).

[0379] Example 10: Characterization of theInula heleniumliquid extracts obtained by maceration according to Examples 5 to 8

[0380] TheInula heleniumliquid extracts nos. 5 to 8, obtained according to the processes described in Examples 5 to 8, are analysed by ultra-performance liquid chromatography (UPLC) under the following conditions:- Equipment: ACQUITY UPLC Waters- Column: Phenomenex (reference Kinetex F5; length 50 mm; particle diameter 2.6 µm; internal diameter 2.1 mm).- Column temperature: 40°C- Eluents:- A: MQ water + 0.05% formic acid- B: Methanol- Flow rate: 0.5 mL / min- Injection volume: 2 μL (sample temperature: 20°C)- PDA detection: 190 - 800 nm.

[0381] Extracts nos. 5, 7 and 8 are diluted to 1 / 50thin a mixture of methanol and of water in a methanol:water ratio of 50:50 (v / v). Extract no. 6 is diluted to 1 / 10thin the same mixture.

[0382] t (minutes)A (%)B (%)09551001001501001695521955Start of the gradient at injection

[0383] Table 2 describes the elution gradient programme used during the UPLC analysis of Example 10.

[0384] Results:

[0385] The chromatograms of the 4Inula heleniumliquid extracts analysed are similar. The same major compounds are found, namely:- fumaric acid (C4H4O4, M = 115 g / mol),- chlorogenic acid (3-CQA, C16H18O9, M = 354 g / mol),- isochlorogenic acid A (3,5-dicaffeoylquinic acid, C25H24O12, M = 516.45 g / mol),- 1,5-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol), and- 4,5-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol).

[0386] Example 11: Extrusion process implemented in Examples 12 to 15

[0387] The extraction of theInula heleniumplant biomass consisting of flowering tops is carried out using a Clextral BC21 corotating intermeshing twin-screw extruder. The extruder is constituted of two screw shafts inserted in barrels equipped with heating shells making it possible to regulate the temperature and to carry out the extraction continuously.A draining module is positioned with filtration screens having a cut-off threshold of 0.8 mm, ensuring the recovery of the filtrate containing the molecules of interest.The solvent injections are carried out in two zones by introduction pump systems. The extraction solvent used is specified in each of Examples 12 to 15.TheInula heleniumplant biomass itself is introduced via a weight metering system (Coperion K-Tron type) at a delivery rate that makes it possible to ensure a defined liquid:solid (L:S) ratio. This ratio is specified in each of Examples 12 to 15.A screw rotation speed of 350 rpm is applied, with a setpoint temperature specified in each of Examples 12 to 15.The filtrate, recovered at the draining module, is conveyed to a centrifugal decanter (Lemitec type). The liquid thus recovered, after the centrifugal decantation, is transferred to a filtering system (plate filter type) equipped with a double filtration stage: 0.6 µm KDS15 and then 0.1 µm BECO Steril S100.The passage time within the extruder is preferably less than 5 minutes.

[0388] Example 12:Inula heleniumliquid extract no. 9obtained by extrusion

[0389] This example repeats the extrusion procedure detailed in Example 11, including the following parameters:- theInula heleniumplant biomass consisting of flowering tops:extraction solvent ratio used is 1:2.9,- the extraction solvent consists of a mixture of water and of 1,3-propanediol in a water:1,3-propanediol ratio by weight of 20:80, and- the temperature applied is 80°C.A liquid extract, amber-brown in colour, is thus obtained (extract no. 9).

[0390] Example 13:Inula heleniumliquid extract no. 10 obtained by extrusion

[0391] This example repeats the extrusion procedure detailed in Example 11, including the following parameters:- theInula heleniumplant biomass consisting of flowering tops:extraction solvent ratio used is 1:2.9,- the extraction solvent consists of a mixture of water and of 1,3-propanediol in a water:1,3-propanediol ratio by weight of 20:80, and- the temperature applied is 95°C.A liquid extract, amber-brown in colour, is thus obtained (extract no. 10).

[0392] Example 14:Inula heleniumliquid extract no. 11 obtained by extrusion

[0393] This example repeats the extrusion procedure detailed in Example 11, including the following parameters:- theInula heleniumplant biomass consisting of flowering tops:extraction solvent ratio used is 1:2,- the extraction solvent consists of a mixture of water and of 1,3-propanediol in a water:1,3-propanediol ratio by weight of 20:80, and- the temperature applied is 80°C.A liquid extract, amber-brown in colour, is thus obtained (extract no. 11).

[0394] Example 15:Inula heleniumliquid extract no. 12 obtained by extrusion

[0395] This example repeats the extrusion procedure detailed in Example 11, including the following parameters:- theInula heleniumplant biomass consisting of flowering tops:extraction solvent ratio used is 1:2.9,- the extraction solvent consists of 1,3-propanediol, and- the temperature applied is 80°C.A liquid extract, dark green to brown in colour and possessing a characteristic odour, is thus obtained (extract no. 12).

[0396] Example 16: Characterization of theInula heleniumliquid extracts obtained by extrusion according to Examples 12 to 15

[0397] TheInula heleniumliquid extracts nos. 9 to 12, obtained according to the processes described in Examples 12 to 15, are analysed by ultra-performance liquid chromatography (UPLC) under the following conditions:- Equipment: ACQUITY UPLC Waters- Column: ACQUITY BEH Shield RP18 (Waters, 100 x 2.1 mm, 1.8 μm)- Column temperature: 40°C- Eluents:- A: MQ water + 0.1% formic acid- B: Acetonitrile + 0.1% formic acid- Flow rate: 0.5 mL / min- Injection volume: 2 μL (sample temperature: 20°C)- PDA detection: 190 - 700 nm- Process: 210 – 700 nm.

[0398] Extracts nos. 9 to 11 are diluted to 1 / 10thin a mixture of methanol and of water in a methanol:water ratio of 50:50 (v / v). Extract no. 12 was injected without dilution.

[0399] t (minutes)A (%)B (%)09911.10205.26634701007.501007.79918.5991Start of the gradient at injection

[0400] Table 3 describes the elution gradient programme used during the UPLC analysis of Example 10.

[0401] Results:

[0402] The chromatograms of the 4Inula heleniumliquid extracts analysed are similar. The same major compounds are found, namely:- fumaric acid (C4H4O4, M = 115 g / mol),- chlorogenic acid (3-CQA, C16H18O9, M = 354 g / mol),- isochlorogenic acid A (3,5-dicaffeoylquinic acid, C25H24O12, M = 516.45 g / mol),- 1,5-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol), and- 4,5-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol).

[0403] Extract no. 9, obtained according to Example 12, comprises, as percentage in the liquid extract relative to dry matter:- 0.385% fumaric acid (C4H4O4, M = 115 g / mol),- 2.718% chlorogenic acid (3-CQA, C16H18O9, M = 354 g / mol),- 3.487% isochlorogenic acid A (3,5-dicaffeoylquinic acid, C25H24O12, M = 516.45 g / mol),- 3.846% 1,5-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol),- 1.795% 4,5-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol),- 0.205% neochlorogenic acid (5-CQA, C16H18O9, M = 354 g / mol),- 0.154% cryptochlorogenic acid (4-CQA, C16H18O9, M = 354 g / mol),- 0.154% 1,3-dicaffeoylquinic acid (C25H24O12, M = 516.45 g / mol), and- 0.410% isochlorogenic acid B (3,4-dicaffeoylquinic acid, C25H24O12, M = 516.45 g / mol).Examples of cosmetic activity

[0404] Example 17: Study of the gene signature of a pro-resolving M2 macrophage obtained by differentiation and polarization of the pro-monocyte THP-1 line

[0405] The pro-monocyte THP-1 line is cultured in an RPMI 1640 medium containing 10% FCS (Eurobio), 1% L-Glutamine-Penicillin-Streptomycin (Gibco) and 0.1% β-mercaptoethanol (50 mM, Gibco).In order to differentiate the monocytes into macrophages, the cells are treated with phorbol 12-myristate 13-acetate (PMA) (Sigma-Aldrich) at 60 ng / mL for 24 hours, and are then cultured in PMA-free medium for 24 hours.The macrophages, treated with 20 ng / mL of IFN-γ (Peprotech) and 0.1 µg / mL of LPS (Sigma-Aldrich), or 20 ng / mL of IL-4 (Peprotech), for 24 hours, are respectively polarized into pro-inflammatory M1 macrophages or into pro-resolving M2 macrophages.RNA from macrophages that are non-polarized (i.e. untreated) or polarized into M1 and M2 macrophages is extracted and the expression of the TNF-α (tumour necrosis factor alpha), PTGS2 (prostaglandin-endoperoxide synthase 2), CD209, CD206 and IL-10 (interleukin 10) mRNAs (Qiagen) is measured by RT-PCR. Each value is corrected by the expression of mRNAs from three housekeeping genes: GAPDH (glyceraldehyde 3-phosphate dehydrogenase), ACTB (actin beta) and RPL13 (ribosomal protein L13).

[0406] Results:

[0407] Table 4 shows the fold-change values of the gene expression of the macrophages treated with IFN-γ and LPS or IL-4 compared to untreated macrophages.M1-polarized, pro-inflammatory macrophages express mRNAs of characteristic inflammatory cytokines such as TNF-α and PTGS2 more strongly than the non-polarized (untreated) macrophages, with a fold change of greater than 9. On the other hand, they underexpress the pro-resolving marker CD206 compared to the untreated macrophages.Markers characteristic of M2-polarized pro-resolving macrophages are overexpressed by the IL-4-treated cells, such as CD209, CD206 and IL-10, cells which also underexpress the inflammatory markers TNF-α and PTGS2 compared to the non-polarized macrophages.These results confirm that macrophages derived from the pro-monocyte THP-1 line are polarized into pro-inflammatory M1 macrophages after treatment with IFN-γ and LPS, or into pro-resolving M2 macrophages after treatment with IL-4.

[0408] Fold change*ProductPTGS2TNF-αCD206CD209IL-10IFN-γ and LPS (M1 macrophages)9.49.5-25.20.20IL-4(M2 macrophages)-5.5-2.29.910.93.9

[0409] *Fold-change values of greater than 1.5 indicate overexpression of the mRNAs of the target genes in the macrophages treated with IFN-γ and LPS or IL-4, compared to the non-polarized (untreated) macrophages. Conversely, negative fold changes starting from -1.5 reflect underexpression of the mRNAs of the target genes in the polarized (treated) macrophages compared to the untreated macrophages. A fold change of between -1.5 and 1.5 indicates that the polarization of the macrophages into M1 or M2 macrophages does not significantly affect the expression of the mRNA of the gene of interest.

[0410] Example 17bis: Study of the gene signature of a pro-resolving M2 macrophage obtained by differentiation of the pro-monocyte THP-1 line followed by shift from a previously polarized pro-inflammatory M1 macrophage

[0411] The pro-monocyte THP-1 line is cultured in an RPMI 1640 medium containing 10% FCS (Eurobio), 1% L-Glutamine-Penicillin-Streptomycin (Gibco) and 0.1% β-mercaptoethanol (50 mM, Gibco).In order to differentiate the monocytes into macrophages, the cells are treated with Phorbol 12-myristate 13-acetate (PMA) (Sigma-Aldrich) at 60 ng / mL for 24 hours, and then cultured in PMA-free medium for 24 hours.Inflammatory M1 phenotype is induced by treating the macrophages with 20 ng / mL of IFN-γ (Peprotech) and 0.1 µg / mL of LPS (Sigma-Aldrich) for 3 hours. After rinsing, macrophages treated with 20 ng / mL of IFN-γ (Peprotech) and 0.1 µg / mL of LPS (Sigma-Aldrich), or 20 ng / mL of IL-4 (Peprotech) for 48 hours are respectively maintained as pro-inflammatory M1 macrophages or shifted to pro-resolving M2 macrophages.RNA from non-polarized macrophages (i.e. untreated), or maintained as M1 or shifted to M2 macrophages, is extracted and the expression of TNF-α (Tumor necrosis factor alpha), PTGS2 (Prostaglandin-endoperoxide synthase 2), AnXA1, PPARgamma, and CD206 (Qiagen) mRNAs is measured by RT-PCR. Each value is corrected by the expression of mRNAs from three housekeeping genes: GADPH (Glyceraldehyde 3-phosphate dehydrogenase), ACTB (Actin beta), and RPL13 (Ribosomal protein L13).

[0412] Results:Table 4bis shows the fold-change values of gene expression in macrophages treated with IFN-γ and LPS or IL-4 compared to untreated macrophages.Pro-inflammatory M1-polarized macrophages express the mRNAs of characteristic inflammatory cytokines such as TNF-α and PTGS2 more strongly compared to macrophages polarized to M1 and then untreated, with a fold change greater than 1.5.Markers characteristic of pro-resolving M2-polarized macrophages are overexpressed by IL-4-treated cells shifted to M2 macrophages, such as AnXA1, CD206, and PPARgamma, cells which also underexpress the inflammatory markers TNF-α and PTGS2 compared to non-polarized macrophages.These results confirm that macrophages derived from the pro-monocyte THP-1 line are polarized to pro-inflammatory M1 macrophages after treatment with IFN-γ and LPS or shifted to pro-resolving M2 macrophages after treatment with IL-4.

[0413] Fold-change*ProductPTGS2TNF-αAnXA1PPARgammaCD206IFN-γ and LPS (M1 macrophages)2.41.6-1.6-1.71IL-4(M2 macrophages)-5.3-0.94.15.911.9

[0414] *Fold-change values of greater than 1.5 indicate overexpression of the mRNAs of the target genes in macrophages treated with IFN-γ and LPS or IL-4, compared to non-polarized (untreated) macrophages. Conversely, negative fold changes starting from -1.5 reflect underexpression of the mRNAs of the target genes in polarized (treated) macrophages compared to untreated macrophages. A fold change between -1.5 and 1.5 indicates that the polarization of macrophages into M1 or M2 does not significantly affect the expression of the mRNA of the gene of interest.

[0415] Example 18: Effect of the treatment of non-polarized macrophages with anInula heleniumdry extract at 0.05 g / L on the expression of specific marker genes of the M1 and M2 profiles

[0416] As described in Example 17, monocytes are differentiated into macrophages. The macrophages are then treated with theInula heleniumdry extract no. 1 obtained according to the abovementioned Example 1 (aqueous-alcoholic maceration at 30%, for 1 h at 50°C) in a DMSO:water mixture (50:50 v / v) at 0.05 g / L for 24 hours.

[0417] RNA from the cells is extracted and the expression of the TNF-α, PTGS2, CD209, CD206 and IL-10 mRNAs (Qiagen) is measured by RT-PCR.

[0418] Results:

[0419] Table 5 shows the fold-change values of the gene expression of the macrophages treated with theInula heleniumdry extract corresponding to Example 1 compared to untreated macrophages.TheInula heleniumdry extract according to the invention significantly decreases the expression of the pro-inflammatory TNF-α and PTGS2 genes by the macrophages, with a fold change of less than -1.5 compared to the untreated macrophages.Moreover, theInula heleniumdry extract no. 1 increases the expression of the pro-resolving markers CD209, CD206 and IL-10 by the macrophages, with a fold change of greater than 1.5 compared to the untreated control.

[0420] These results demonstrate thatInula heleniumin the form of a dry extract according to the invention has pro-resolving effects since it promotes the polarization of the macrophages towards a pro-resolving M2 profile to the detriment of a pro-inflammatory M1 profile.

[0421] Fold changeProductPTGS2TNF-αCD206CD209IL-10Inula heleniumdry extract no. 1-2.3-2.91.92.015.1

[0422] Example 18bis: Effect of treating pro-inflammatory M1 macrophages with a dry extract ofInula heleniumat 0.05 g / L on the expression of marker genes specific to M1 and M2 profiles

[0423] As described in Example 17bis, monocytes are differentiated into macrophages and then polarized into inflammatory M1 macrophages for 3 hours. The macrophages are then treated with theInula heleniumdry extract no. 1 obtained according to Example 1 mentioned above (hydroalcoholic maceration at 30% for 1 hour at 50°C) in a DMSO:water mixture (50:50 v:v) at 0.05 g / L for 48 hours.The RNA of the cells is extracted and the expression of TNF-α, PTGS2, AnXA1, CD206, and PPARgamma mRNAs (Qiagen) is measured by RT-PCR.

[0424] Results:Table 5bis shows the fold-change values of the gene expression of macrophages treated with theInula heleniumdry extract corresponding to Example 1 compared to untreated macrophages.TheInula heleniumdry extract according to the invention significantly decreases the expression of the pro-inflammatory gene TNF-α in macrophages with a fold-change of less than -1.5 compared to untreated macrophages.Furthermore, theInula heleniumdry extract no. 1 increases the expression of pro-resolving markers PPARgamma, AnXA1, and CD206 in macrophages with a fold-change greater than 1.5 compared to the untreated control.These results demonstrate thatInula heleniumin dry extract form according to the invention has pro-resolving effects even in an inflammatory environment since it promotes the shift of macrophages to a pro-resolving M2 profile from a pro-inflammatory M1 profile.

[0425] Fold-changeProductPTGS2TNF-αAnXA1CD206PPARgammaInula helenium dry extractno.11-3.72.33.23.3

[0426] Example 19: Effect of the treatment of non-polarized macrophages with anInula heleniumliquid extract at 1 g / L on the expression of specific marker genes of the M1 and M2 profiles

[0427] As described in Example 17, monocytes are differentiated into macrophages. The macrophages are then treated with theInula heleniumliquid extract n°9 obtained according to the abovementioned Example 12 (extrusion as a 1,3 propanediol:water mixture (ratio by weight of 80:20) at 80°C with an L:S ratio of 2.9) in DMSO at 1 g / L for 24 hours.

[0428] RNA from the cells is extracted and the expression of the CD209 and IL-10 mRNAs (Qiagen) is measured by RT-PCR.

[0429] Results:

[0430] Table 6 shows the fold-change values of the gene expression of the macrophages treated with theInula heleniumliquid extract corresponding to Example 12 compared to untreated macrophages.

[0431] TheInula heleniumliquid extract according to the invention increases, in the cultured macrophages, the expression of the pro-resolving markers CD209 and IL-10, characteristic of macrophages polarized towards an M2 profile, with a fold change of greater than 1.5 compared to the untreated control.

[0432] These results demonstrate thatInula heleniumin the form of a liquid extract according to the invention has pro-resolving effects since it promotes the polarization of the macrophages towards an M2 profile.

[0433] Fold changeProductCD209IL-10Inula heleniumliquid extract no. 923.6

[0434] Example 19bis: Effect of treating non-polarized macrophages with a liquid extract ofInula heleniumat 1 g / L on the expression of specific marker genes of M1 and M2 profiles

[0435] As described in Example 17bis, monocytes are differentiated into macrophages and then polarized into inflammatory M1 macrophages for 3 hours. The macrophages are then treated with liquid extract ofInula heleniumno. 9 obtained according to the aforementioned Example 12 (Extrusion in a mixture of 1,3 propanediol:water (weight ratio of 80:20) at 80°C with L:S ratio of 2.9) in DMSO at 1 g / L for 48 hours.

[0436] RNA is extracted from the cells and the expression of AnXA1, CD206, and PPARgamma mRNAs (Qiagen) is measured by RT-PCR.

[0437] Results:

[0438] Table 6bis shows the fold-change values of gene expression in macrophages treated with the liquid extract ofInula heleniumcorresponding to Example 12 compared to untreated macrophages.

[0439] The liquid extract ofInula heleniumaccording to the invention increases in cultured macrophages the expression of pro-resolutive markers AnXA1, CD206, and PPARgamma mRNAs, characteristic of macrophages polarized towards an M2 profile, with a fold change greater than 1.5 compared to the untreated control.

[0440] These results demonstrate thatInula heleniumin liquid extract form according to the invention has pro-resolutive effects as it promotes the shift of pro-inflammatory M1 macrophages towards pro-resolutive M2 macrophages.

[0441] Fold-changeProductAnXA1CD206PPARgammaInula heleniumliquid extract n°912.143.142.35

[0442] Example 20: Treatment of a co-culture of dendritic cells and keratinocytes with anInula heleniumdry extract at 0.01 g / L and measurement of specific pro-resolving lipid mediators

[0443] TheInula heleniumextract no. 1, obtained according to Example 1 (aqueous-alcoholic maceration at 30% for 1 hour at 50°C) is tested in order to measure its capacity for inducing the production of pro-resolving mediators, key markers of pro-resolution, in a model of co-culture of dendritic cells and keratinocytes.

[0444] To do this, dendritic cells at the bottom of culture wells are placed in co-culture with keratinocytes seeded in inserts. The co-culture is incubated for 24 hours with theInula heleniumdry extract at 0.01 g / L. The cells are rinsed and are then incubated for 1 hour in the presence of an inflammation-inducing cocktail containing PMA and calcium ionophore. The culture supernatants are recovered and analysed by LC-MS / MS for 14 pro-resolving lipid mediators sought in the following three pathways:(i) arachidonic acid (ARA) pathway: lipoxins A4 and B4 (LxA4 and LxB4),(ii) docosahexaenoic acid (DHA) pathway: maresins 1 and 2 (Mar-1, Mar-2), protectins D1 and DX (PD1 and PDX) and resolvins D1, D2, D3, D4 and D5 (RvD1, RvD2, RvD3, RvD4, RvD5), and(iii) eicosapentaenoic acid (EPA) pathway: resolvins E1, E2 and E4 (RvE1, RvE2, RvE4).

[0445] Results:

[0446] Table 7 shows the percentage activation of the various specialized pro-resolving mediators (SPMs) quantified in the supernatants of the co-culture of dendritic cells and keratinocytes treated with theInula heleniumdry extract corresponding to Example 1, compared with the untreated condition.

[0447] This analysis shows that theInula heleniumdry extract according to the invention significantly increases the secretion by the cells in co-culture of several pro-resolving lipid mediators: lipoxin A4 (LXA4), maresin 2 (Mar 2), resolvin D1 (RvD1) and resolvin E4 (RvE4).

[0448] These results show that theInula heleniumextract according to the invention is not limited to an action on the macrophages at the level of the skin by promoting their polarization towards an M2 profile, but also acts on the skin cells by stimulating their production of pro-resolving mediators.

[0449] Metabolic pathwayARADHAEPASPMsLXA4Mar 2RvD1RvE4% activation1309244831p-value0.0010.0010.090.001

[0450] Example 20bis: Treatment of a co-culture of dendritic cells and keratinocytes with a liquid extract ofInula heleniumat 1 g / L and measurement of specific lipid mediators of pro-resolution

[0451] TheInula heleniumextract no. 9, obtained according to the aforementioned Example 12 (Extrusion in a mixture of 1,3 propanediol:water (weight ratio of 80:20) at 80°C with L:S ratio of 2.9) is tested to measure its capacity to induce the production of pro-resolving mediators, indispensable markers of pro-resolution, in a co-culture model of dendritic cells and keratinocytes.

[0452] For this, dendritic cells in the bottom of culture wells are co-cultured with keratinocytes seeded in inserts. The co-culture is incubated for 24 hours with the liquid extract ofInula heleniumat 1 g / L. The cells are then rinsed and incubated for 1 hour in the presence of a pro-inflammatory inducer cocktail, containing PMA and calcium ionophore. The culture supernatants are collected and analyzed by LC-MS / MS for 14 pro-resolving lipid mediators sought in the following three pathways:

[0453] (i) arachidonic acid pathway (ARA): lipoxins A4 and B4 (LxA4 and LxB4),

[0454] (ii) docosahexaenoic acid pathway (DHA): maresins 1 and 2 (Mar-1, Mar-2), protectins D1 and DX (PD1 and PDX) and resolvins D1, D2, D3, D4, and D5 (RvD1, RvD2, RvD3, RvD4, RvD5), and

[0455] (iii) eicosapentaenoic acid pathway (EPA): resolvins E1, E2, and E4 (RvE1, RvE2, RvE4).

[0456] Results:

[0457] Table 7bis shows the percentage activation of the various specialized pro-resolving mediators (SPMs) quantified in the supernatants of the co-culture of dendritic cells and keratinocytes treated with the liquid extract ofInula heleniumcorresponding to Example 12 compared to the untreated condition.

[0458] This analysis shows that the liquid extract ofInula heleniumaccording to the invention significantly increases the secretion of several pro-resolving lipid mediators by the co-culture cells: lipoxin A4 (LXA4), resolvin D5 (RvD5) as well as resolvin E2 (RvE2).

[0459] These results demonstrate that theInula heleniumextract according to the invention not only acts on macrophages in the skin by promoting their polarization and shift towards an M2 profile, but also acts on skin cells by stimulating their production of pro-resolving mediators.

[0460] Metabolic pathwayARA DHA EPASPMsLXA4RvD5RvE2% activation301051025p-value0.050.050.05

[0461] Example 21: Effect of treating non-polarized or pro-inflammatory macrophages with the most polar fraction of driedInula heleniumextract corresponding to 0.05 g / L on the expression of specific marker genes of M1 and M2 profiles

[0462] A / - Fractionation of the driedInula heleniumextract obtained according to Example 1Objective

[0463] This protocol describes the fractionation of an hydroalcoholic dry extract ofInula heleniumobtained according to example 1 using Solid Phase Extraction (SPE),

[0464] followed by solvent evaporation and lyophilization, to isolate a specific fraction (F6).Materials and Reagents

[0465] Acetonitrile (ACN): LC-MS grade (Fisher Scientific); Ultrapure Water: Purified to a resistivity of 18.2 MΩ·cm by a MilliQ system (Merck Millipore Water); Methanol (MeOH): LC-MS grade (Fisher Scientific); Hydroalcoholic dry extract obtained according to example 1 :Ethanol / ultrapure water (30 / 70); SPE Cartridge: SEP Pack C18 10 cc (Waters); Centrifuge Tube: Falcon® 45 mL; Genevac (Biopharma Technologie) lyophilizer.Fractionation method

[0466] 400 mg of hydroalcoholic dry extract obtained according to example 1 was introduced into an appropriate vessel. This was followed by adding 4 mL of an acetonitrile (ACN) / ultrapure water (25 / 75) mixture, and subsequently, 16 mL of ultrapure water (100%). The mixture was then subjected to sonication for 15 minutes, resulting in a solution with a concentration of 20 mg / mL in an ACN / Water mixture (5 / 95). This solution was transferred into a 45 mL Falcon® centrifuge tube and centrifuged for 10 minutes at 10,000 rpm. SPE cartridge was conditioned using 30 mL of methanol (MeOH, 100%), followed by 45 mL (3 x 15 mL) of water / MeOH (95 / 5). SPE fractionation steps involved: 1) Loading 20 mL of the supernatant obtained from the centrifugation step onto the conditioned SPE cartridge; 2) Eluting with 20 mL of 5% MeOH; 3) Eluting with 15 mL of 5% MeOH; 4) Eluting with 3 x 15 mL of 10% MeOH; 5) Eluting with 3 x 15 mL of 40% MeOH; and 6) Eluting with 45 mL of pure MeOH (100%), where this fraction, designated F6, was collected. Finally, MeOH from the collected F6 fraction was evaporated using a rotavapor. The dry extract was redissolved in 28 mL of ethanol, the flask was rinsed with 32 mL of ultrapure water, and the ethanol and water fractions (totaling 60 mL) were combined. The combined fractions were then lyophilized.

[0467] The mass yield for fraction F6 was 11% based on 3 fractionation experiments.

[0468] B / - Identification of the compounds of the fraction obtained in step A / -Objective

[0469] The UPLC / HRMS / MS analysis used to identify compounds of fraction F6 and Exform extract is described below.Sample preparation

[0470] 5.5 mg of fraction F6 was solubilized in 0.5 mL of a Dimethyl sulfoxide (DMSO) / ultrapure water (50 / 50) mixture, subsequently diluted at 1.0 mg / mL in ultra pure water (100%).Analysis method

[0471] Acquisitions were realized on an Orbitrap Exploris240 high-resolution mass spectrometer (HRMS) equipped with an electrospray source (ESI), an Ultimate 3000 ultra-high-performance liquid chromatography (UPLC) system, and a photodiode-array detector (PDA)from Thermo Fisher Scientific. Separation was achieved on an ACQUITY BEH Shield RP18 (Waters, 100*2.1 mm, 1.8 μm) at 35°C.Mobile phases used were water and ACN both acidified with 0.1% of formic acid. The gradient used was as follows: 0 - 1 min: 1% ACN,1 - 15 min: 1 to 100% ACN, 15 - 20 min: 100% ACN, 20.1 - 25 min: 1% ACN, at a flow rate of 0.6 mL / min. The autosampler was set at10°C. The injection volume was 2 μL. The wavelength range of the PDA detector was 190 - 700 nm. Acquisitions were performed on scan range m / z 100 – 1100 operated separately in positive (+3.8 kV) and negative (-3.4 kV) ion modes. ESI source parameters were set as follows: vaporizer temperature: 400°C, capillary transfer tube temperature: 325°C, sheath gas pressure: 30 arbitrary units, auxiliary gas: 10 arbitrary units, sweep gas: 2 arbitrary units. The RF Lens was set at 60%. Analyses were performed using full scan mode, and full scan MS – data-dependent MS2 mode (ddMS2), with non-resonant excitation mode higher-energy collisional dissociation (HCDstepped at 15-25-35%). The mass spectrometer was calibrated prior to analysis with PierceTM FlexMixTM calibration solution (Thermo Fisher Scientific, reference A39239). The mass resolution power of the analyzer was 120,000 m / Δm, full width at half maximum (FWHM) at m / z 200, for singly charged ions. All the data were manually inspected using Thermo Fisher Sci-entific software:Freestyle module of Xcalibur (version 4.4), Compound Discoverer (version 3.3) in combination with product ion spectral databasemzCloud (2024 update) and an in-house mzVault database.

[0472] CompoundsCAS numberRaw formulaCostunolide553-21-9C15H20O22 alpha hydroxy alantolactone2998963-70-3C15H20O34,5-Epoxy-10,14-dihydroinuviscolide68776-54-5C15H20O3Dehydroivaxilin87441-73-4C15H20O4Quercetin117-39-5C15H20O710 hydroxy 14H inuviscolide171964-43-5C15H22O43 O methylquercetin1486-70-0C16H12O7Kaempferol 3 O glucoside480-10-4C21H20O11Quercetin 3 O glucoside482-35-9C21H20O12Hyperoside / quercetin 3 D galactoside482-36-0C21H20O12Isorhamnetin 3 O glucoside5041-82-7C22H22O124,5 Dicaffeoylquinic acid89886-31-7C25H24O121,5 Dicaffeoylquinic acid19870-46-3C25H24O121,4 Dicaffeoylquinic acid1182-34-9C25H24O123,5 Dicaffeoylquinic acid2450-53-5C25H24O12Atractyligenin 2-O-glucoside62022-40-6C25H38O9Kaempferol rutinoside17650-84-9C27H30O153,4,5 tricaffeoylquinic acid86632-03-3C34H30O15

[0473] * Identified with highest level of confidence using raw formula, MS / MS spectra, retention time in comparison with authentic compounds or using NMR data, according to recommendations from the Chemical Analysis Working Group (CAWG) (Sumner, L.W.; Amberg, A.; Barrett, D.; Beale, M.H.; Beger, R.; Daykin, C.A.; Fan, T.W.; Fiehn, O.; Goodacre, R.; Griffin, J.L.; et al. Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI). Metabolomics 2007, 3, 211–221).

[0474] C / - Effect of the most polar fraction of driedInula heleniumon non-polarized or pro-inflammatory macrophages

[0475] As described in Example 17 and 17bis, monocytes are differentiated into macrophages and then maintained as non-polarized M0 macrophages or transformed into M2 macrophages. The macrophages are then treated with the fraction F6 obtained according to point A of Example 21 in a DMSO:water mixture (50:50 v:v) corresponding to theInula heleniumfraction at 0.05 g / L for 24 hours.

[0476] RNA is extracted from the cells and the expression of TNF-α, AnXA1, CD209, and PPARgamma mRNAs (Qiagen) is measured by RT-PCR.

[0477] Results:

[0478] Table 9 shows the fold-change values of gene expression in macrophages treated with the fraction F6 and prepared according to the polarization protocol of Example 17 or the shift protocol of Example 17bis compared to untreated macrophages.

[0479] The fraction F6 according to the invention significantly decreases the expression of the pro-inflammatory gene TNF-α in macrophages with a fold-change less than -1.5 compared to untreated macrophages.

[0480] Furthermore, the fraction F6 increases the expression of pro-resolving markers CD209, AnXA1, and PPARgamma in macrophages with a fold-change greater than 1.5 compared to the untreated control in both protocols.

[0481] These results demonstrate that the fraction F6 in dried extract form is the part that carries the pro-resolutive effects as it promotes the polarization or shift of macrophages towards a pro-resolutive M2 profile at the expense of a pro-inflammatory M1 profile.

[0482] Fold-changeProductTNF-αAnXA1CD209PPARgammaF6 fractionpolarization protocol-26.72.22.54.4F6 fractionshift protocol-12.43.3118

[0483] Example 22: Syrupobtained with the extract according to Example 5

[0484] SyrupActive%Extract ofInula heleniumobtained according to example 51ExcipientWater55Cane sugar38.5Ethanol5Xanthan gum0.5

[0485] Example 23:Syrup obtained with the extract according to Example 6

[0486] SyrupActive%Inula heleniumobtained according to example 61.5ExcipientWater55Cane sugar38Ethanol5Xanthan gum0.5

[0487] Example24:Syrup obtained with the extract according to Example 1

[0488] SyrupActive%Inula heleniumextract obtained according to example 10.5ExcipientWater55Cane sugar39Ethanol5Xanthan gum0.5

[0489] Example25:Syrup obtained with the extract according to Example2

[0490] SyrupActive%Inula heleniumextract obtained according to example 21 ExcipientWater55Cane sugar38.5Ethanol5Xanthan gum0.5

[0491] Example 26:Coated tablet obtained with the extract according to Example 1

[0492] Coated tablet formulationActivemg / tabletInula heleniumextract obtained according to example 150Excipient in the tablet coreMicrocrystalline cellulose70Encompress ™60Magnesium stearate3Colloidal anhydrous silica1Coating agentShellac5Talc61Sucrose250Polyvidone6Titanium dioxide0.3Coloring agent5

[0493] Example 27:Coated tablet obtained with the extract according to Example 2

[0494] Coated tablet formulationActivemg / tabletInula heleniumextract obtained according to example 2100Excipient in the tablet coreMicrocrystalline cellulose70Encompress ™60Magnesium stearate3Colloidal anhydrous silica1Coating agentShellac5Talc61Sucrose200Polyvidone6Titanium dioxide0.3Coloring agent5

[0495] Example 28:Coated tablet obtained with the extract according to Example3

[0496] Coated tablet formulationActivemg / dragéeInula heleniumextract obtained according to example 325Excipient in the tablet coreMicrocrystalline cellulose70Encompress ™60Magnesium stearate3Colloidal anhydrous silica1Coating agentShellac5Talc61Sucrose275Polyvidone6Titanium dioxide0.3Coloring agent5

Claims

1.Process for obtaining a plant extract of flowering tops ofInula helenium, comprising the steps consisting of:a) bringing at least one plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniuminto contact with an extraction solvent comprising at least one cosmetically acceptable organic solvent,at an extraction temperature lower than the boiling point of the extraction solvent at atmospheric pressure,in particular, the duration of step a) being between 10 seconds and 5 hours; andb) removing the plant biomass residues, in particular by decantation and / or filtration.2.Process for obtaining a plant extract comprising, and in particular consisting of, flowering tops ofInula helenium, comprising the steps consisting of:a) bringing at least one plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniuminto contact with an extraction solvent consisting of water at an extraction temperature of between 40°C and 90°C, in particular between 45°C and 85°C, and more particularly of about 50°C,in particular, the duration of step a) being between 10 seconds and 5 hours; andb) removing the plant biomass residues, in particular by decantation and / or filtration.3.Process according to Claim 1 or 2, wherein the plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniumof step a) comprises, and in particular is constituted of, flowering tops ofInula heleniumharvested at the full bloom stage, and in particular flowering tops ofInula heleniumharvested at the full bloom stage and dried and / or ground.4.Process according to any one of the preceding claims, wherein the plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniumof step a) is dried during a step a’) prior to implementing step a), for at least about 24 hours, in particular for about 72 hours, at a drying temperature of between 30°C and 60°C, in particular between 30°C and 50°C, more particularly between 30°C and 40°C, especially of about 35°C.5.Process according to any one of the preceding claims, wherein the plant biomass comprising, and in particular consisting of, flowering tops ofInula heleniumof step a) is ground during a step a’’) prior to implementing step a), with a particle size of between 2 cm and 0.1 mm, preferably between 1 cm and 0.5 mm, more particularly between 4 mm and 1 mm, in particular with a particle size of about 2 mm.6.Process according to any one of the preceding claims, wherein step a) is an extraction step selected from a maceration step, an extrusion step or a percolation step, and is in particular a maceration step or an extrusion step.7.Process according to any one of Claims 1 and 3 to 6, wherein said at least one cosmetically acceptable organic solvent is selected from the group consisting of polar protic organic solvents, such as ethanol, propanediol, glycerol, butanediol, and mixtures thereof; and / or from the group consisting of polar aprotic organic solvents, such as acetone, ethyl acetate, and mixtures thereof.8.Process according to any one of Claims 1 and 3 to 7, wherein the extraction solvent additionally comprises water and the cosmetically acceptable organic solvent is miscible with water, the extraction solvent preferably consisting of at least one water-miscible cosmetically acceptable organic solvent and water, the cosmetically acceptable organic solvent and the water in particular being in a water:cosmetically acceptable organic solvent(s) ratio by weight of between 5:95 and 95:5, preferably 10:90 and 90:10, more preferentially between 15:85 and 85:15, even better still between 17:83 and 83:17, more particularly 70:30 or 20:80, in particular 50:50 or 60:40 or 80:20.9.Process according to any one of Claims 1 and 3 to 8, wherein the at least one cosmetically acceptable, preferably polar protic or aprotic, more preferentially protic, organic solvent is present in the extraction solvent in a content of between 5% and 95% by weight relative to the total weight of the extraction solvent, preferably a content of between 10% and 90% by weight, more preferentially between 15% and 85% by weight, even better still between 17% and 83% by weight relative to the total weight of the extraction solvent.10.Process according to any one of Claims 1 and 3 to 9, wherein the at least one cosmetically acceptable, preferably polar protic or aprotic, more preferentially protic, organic solvent is present in the extraction solvent in a content of 100% by weight relative to the total weight of the extraction solvent.11.Process according to any one of Claims 1 and 3 to 10, wherein:- the extraction temperature of step a) is between 10°C and 95°C, preferably between 20°C and 95°C, especially between 40°C and 90°C, in particular between 45°C and 85°C, and is more particularly about 50°C or about 80°C; and / or- the duration of step a) is between 30 seconds and 3 hours, in particular between 1 minute and 2 hours, and more particularly between 90 seconds and 1 hour.12.Process according to any one of Claims 1 and 3 to 11, wherein:- step a) is a maceration step,- the extraction solvent comprising, and in particular consisting of, at least one cosmetically acceptable, preferably polar protic or aprotic, more preferentially protic, organic solvent, more particularly selected from ethanol, propanediol, and mixtures thereof, and optionally water, in particular consisting of water and at least one cosmetically acceptable, preferably polar protic or aprotic, more preferentially protic, organic solvent, selected from ethanol, propanediol, and mixtures thereof, in particular in a water:[ethanol and / or propanediol] ratio by weight of greater than or equal to 20:80, in particular a water:[ethanol and / or propanediol] ratio by weight of about 30:70, 40:60, 50:50, 60:40, 70:30 or 80:20;- the duration of step a) being between 10 minutes and 5 hours, in particular between 20 minutes and 1 hour; and- the extraction temperature being greater than or equal to 40°C, in particular being about 50°C or about 80°C.13.Process according to any one of Claims 1 and 3 to 11, wherein:- step a) is an extrusion step;- the extraction solvent comprising, and in particular consisting of, at least one cosmetically acceptable, preferably polar protic or aprotic, more preferentially protic, organic solvent, in particular selected from ethanol, glycerol, propanediol, and mixtures thereof, and optionally water, it being understood that, when the extraction solvent comprises water, the water:cosmetically acceptable organic solvent(s) ratio by weight is less than or equal to 1:1, and said cosmetically acceptable organic solvent is miscible with water;- in particular, step a) is carried out with anInula heleniumplant biomass:extraction solvent ratio by weight ranging between 1:2 and 1:5, in particular between 1:2.2 and 1:4, more particularly between 1:2.5 and 1:3, said ratio being in particular about 1:2.9;- the duration of step a) being in particular less than 5 minutes; and- the extraction temperature being between 40°C and 95°C, more preferentially between 45°C and 85°C, more preferentially still between 50°C and 85°C, and in particular being about 80°C.14.Process according to Claim 13, wherein the extraction solvent consists of at least one cosmetically acceptable, preferably polar protic or aprotic, more preferentially protic, organic solvent, in particular selected from ethanol, glycerol, propanediol, and mixtures thereof, and optionally water, said extraction solvent preferably being selected from a mixture of water and of ethanol, a mixture of water and of propanediol, a mixture of water and of glycerol, or propanediol, it being understood that, when said extraction solvent comprises water, the cosmetically acceptable organic solvent is miscible with water and the water:cosmetically acceptable organic solvent(s) ratio by weight is preferably between 5:95 and 1:1 such as 20:80, said extraction solvent preferably consisting of a water-propanediol mixture in a water:propanediol ratio by weight preferably of between 5:95 and 1:1 such as 20:80.15.Process according to any one of the preceding claims, wherein step b) of removing the plant biomass residues comprises:- at least one step b’) of decantation, optionally centrifugal decantation, the supernatant obtained at the end of the decantation step being isolated; and / or- at least one step b’’) of filtration with at least one filter making it possible to obtain a filtrate, said filter(s) individually having a cut-off threshold of between 0.1 microns and 500 microns, in particular multiple filtration steps sequentially employing one or more filters, in particular with cut-off threshold(s) individually of between 50 and 500 microns and / or of between 0.1 and 25 microns, such as 0.2 microns.16.Process according to any one of the preceding claims, characterized in that it additionally comprises a step c), after step b), b’) and / or b’’), of total or partial removal of the residual extraction solvent present in the filtrate obtained at the end of step b), b’) and / or b’’).17.Inula heleniumplant extract obtained by the obtainment process according to any one of Claims 1 to 16, said extract being in solid or liquid form.18.Solid or liquidInula heleniumplant extract, in particular plant extract of flowering tops ofInula helenium, characterized in that it comprises:(i) optionally fumaric acid, and / or a salt thereof, in particular in a content of between 0.05% and 3.5% by weight relative to the total weight of dry matter in the plant extract;(ii) chlorogenic acid, and / or a salt thereof, in particular in a content of between 1.5% and 4% by weight relative to the total weight of dry matter in the plant extract;(iii) cryptochlorogenic acid, and / or a salt thereof, in particular in a content of between 0.25% and 1.5% by weight relative to the total weight of dry matter in the plant extract;(iv) neochlorogenic acid, and / or a salt thereof, in particular in a content of between 0.01% and 0.7% by weight relative to the total weight of dry matter in the plant extract;(v) 1,5-dicaffeoylquinic acid, and / or a salt thereof, in particular in a content of between 1.5% and 5% by weight relative to the total weight of dry matter in the plant extract;(vi) isochlorogenic acid B, and / or a salt thereof, in particular in a content of between 0.1% and 0.5% by weight relative to the total weight of dry matter in the plant extract;(vii) isochlorogenic acid A, and / or a salt thereof, in particular in a content of between 0.4% and 5% by weight relative to the total weight of dry matter in the plant extract;(viii) 4,5-dicaffeoylquinic acid, and / or a salt thereof, in particular in a content of between 0.1% and 6% by weight relative to the total weight of dry matter in the plant extract; andfurther comprises Costunolide; 2 alpha hydroxy alantolactone; 4,5-epoxy-10,14-dihydroinuviscolide; Dehydroivaxilin; 10-hydroxy-14H inuviscolide; 3-O-methylquercetin; Kaempferol 3-O-glucoside; Quercetin 3-O-glucoside; Hyperoside (quercetin 3-D-galactoside); Isorhamnetin 3-O-glucoside; 1,4-dicaffeoylquinic acid; 3,5-dicaffeoylquinic acid; Atractyligenin 2-O-glucoside; Kaempferol rutinoside; and / or 3,4,5-tricaffeoylquinic acid.19.Inula heleniumplant extract according to Claim 18, additionally comprising:(ix) at least one polyphenol, and / or a salt thereof, in particular in a content of between 10% and 20% by weight relative to the total weight of dry matter in the plant extract, wherein the at least one polyphenol is different from chlorogenic acid; cryptochlorogenic acid; neochlorogenic acid; 1,5-dicaffeoylquinic acid; isochlorogenic acid B; isochlorogenic acid A; 4,5-dicaffeoylquinic acid; 1,4-dicaffeoylquinic acid; 3,5-dicaffeoylquinic acid; 3,4,5-tricaffeoylquinic acid; 3-O-methylquercetin; Kaempferol 3-O-glucoside; Quercetin 3-O-glucoside; Hyperoside (quercetin 3-D-galactoside); Isorhamnetin 3-O-glucoside and Kaempferol rutinoside; and / or(x) at least one (poly)amino acid; and / or(xi) at least one (poly)saccharide.20.Composition, in particular cosmetic composition, characterized in that it comprises, in a physiologically acceptable medium, at least oneInula heleniumplant extract as defined in any one of Claims 17 to 19.21.Use of a plant extract as defined according to any one of Claims 17 to 19, or of a composition according to Claim 20, administered by oral or topical route, for preventing and / or treating a chronic inflammatory skin disorder, in particular selected from the group consisting of:- a pigmentary disorder, in particular (i) a pigmentary spot, in particular an actinic lentigo, or (ii) post-inflammatory hyperpigmentation, in particular associated with a scar or with an unaesthetic disorder consecutive to an inflammatory skin manifestation, in particular a scar or an acne mark, a scar or a rosacea mark or (iii) melasma.22.Use according to Claim 21, characterized in that said composition is presented in the form of a food supplement, in particular as soft capsules or capsules, banded capsules, dragees, syrup, gummies, gels, dry or liquid emulsions, tablets, powders for reconstitution, or drinkable ampoules, or as an enriched food product.23.Use according to Claim 22, characterized in that said composition further comprise at least one edible excipient selected from colorants, sweeteners, bulking agents, binders, and preservatives.24.Process for the cosmetic treatment of a keratin material, comprising the application, in particular topical application, to said keratin material of a plant extract as defined according to any one of Claims 17 to 19, or of a composition according to Claim 20.