WO2024012787A1 - Composition comprenant un extrait de jasminum sambac et son utilisation - Google Patents

Composition comprenant un extrait de jasminum sambac et son utilisation Download PDF

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Publication number
WO2024012787A1
WO2024012787A1 PCT/EP2023/065787 EP2023065787W WO2024012787A1 WO 2024012787 A1 WO2024012787 A1 WO 2024012787A1 EP 2023065787 W EP2023065787 W EP 2023065787W WO 2024012787 A1 WO2024012787 A1 WO 2024012787A1
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Prior art keywords
extract
skin
composition
water
weight
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PCT/EP2023/065787
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English (en)
Inventor
Caroline MAKERRI
Hanane CHAJRA
Benoit Mignard
Christophe GONINDARD
Mathilde FRECHET
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Clariant International Ltd
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Publication of WO2024012787A1 publication Critical patent/WO2024012787A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/007—Preparations for dry skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A61Q7/02—Preparations for inhibiting or slowing hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine

Definitions

  • Composition comprising an extract of Jasminum sambac and use thereof
  • the present invention relates to an extract of the leaves of Jasminum sambac comprising iridoid glycosides comprising at least a sambacoside A and molihuasides, a composition comprising such extract and uses thereof. Furthermore, the present invention refers to a cosmetic or pharmaceutic composition comprising such extract as an active ingredient for skin care and for inhibiting hair growth.
  • the skin barrier function prevents the penetration of harmful substances into the deeper viable layers of the skin, it prevents the water loss from the skin as well.
  • the skin harbors microbiota composed by resident commensals, usually non pathogenies, and pathogens microflora. Resident commensals microbiota are known to prevent pathogenic organisms from colonizing the skin surface, either by secreting chemicals by their own or by stimulating the skin’s immune system.
  • Skin dysbiosis has been linked with several skin diseases including atopic dermatitis, acne, rosacea, cellulitis, impetigo, ecthyma, folliculitis, boils.
  • atopic dermatitis the dysbiosis is due to the development of strain Staphylococus aureus while in acne vulgaris, it is Cutibacterium acnes.
  • the skin expresses a variety of antimicrobial peptides (AMPs) which are expressed constitutively and induced in response to pathogenic microbial stimuli.
  • AMPs antimicrobial peptides
  • defensins are peptides known for their antimicrobial activity. Defensins are key elements in the innate immune system of many organisms, the first line of defense against invading pathogens. Indeed, defensins have broad anti-microbial activity against Gram-negative and Gram-positive bacteria, yeast, and some enveloped viruses. For example skin can stimulate the release of Human beta Defensin-2 and 3 (h
  • S100A7 psoriasin
  • controlling microbial colonization such as S. aureus or C. acnes is a major mean to preserve skin symbiosis in healthy skin, or to restore skin symbiosis after its alteration, or to restore the skin healthiness.
  • the skin barrier function deteriorates easily under various harmful conditions such as aging, genetic diseases (e.g., atopic dermatitis, xerosis), immune deregulation, skin dysbiosis, environmental stresses, such as UV-rays, polluants, etc.
  • genetic diseases e.g., atopic dermatitis, xerosis
  • immune deregulation e.g., immune deregulation
  • skin dysbiosis e.g., skin dysbiosis
  • environmental stresses such as UV-rays, polluants, etc.
  • ensuring the preservation of skin healthiness typically involves the preservation of the skin barrier function.
  • the healthy state of the skin depends mainly on the preservation of its microbiome symbiosis and it is characterized by a good hydration maintenance.
  • Skin hydration may be maintained through the production of natural moisturizing factors (NMF) from filaggrin proteolysis by Bleomycin Hydrolase enzyme (BLMH), skin retains water thanks to rather highly hydrophilic molecules such as hyaluronic acid and proteolycans.
  • NMF moisturizing factors
  • BLMH Bleomycin Hydrolase enzyme
  • autophagy Another biological mechansim that may be of interest for skin healthiness is the autophagy process. Indeed, autophagy may be involved inepidermal renewal and differentiation process.
  • Atopic dermatitis typically has the clinical symptoms consisting of dry and pruritic skin.
  • AD is often mainly caused by filaggrin deficiencies, S. aureus colonization, and chronic inflammation due to a defective innate immunity and the proliferation of S. aureus.
  • a deficient skin barrier function is typically established in the pathogenesis of this disease. Indeed, the altered skin barrier function may allow the deep penetration of S. aureus and predispose to its colonization.
  • lower levels of AMPs are often associated with a defective innate immunity.
  • IL- 1 lnterleukin-1
  • IL-8 lnterleukin-8
  • TNF-a Tumor Necrosis Factor-alpha
  • Acne vulgaris typically involves the pilosebaceous unit and characterized by comedones, papules and caused by inflamed and infected skin.
  • Acne typically is a multifactorial skin disease: skin inflammation, C. acnes proliferation, increase sebum production, hyperkeratinization, a poor skin barrier function.
  • C. acnes promotes inflammation through the activation in keratinocytes and immune cells of toll like receptors pathways thus in turn induce the synthesis of proinflammatory cytokines such as IL-1 , IL-6, IL-8 and TNF.
  • Topical retinoids and antibiotics are well known in the treatment of atopic dermatitis.
  • these drugs have many drawbacks mainly the antibiotics which further worsens skin and intestinal microbiota dysbiosis, and antibiotics resistance as well.
  • skin diseases such as pityriasis versicolor, seborrheic dermatitis, atopic dermatitis, psoriasis but also dandruff are known to be caused by microorganisms such as Malassezia yeasts.
  • Hypertrophic scars and keloids known as skin fibrotic diseases, represent a dysregulated response to cutaneous wounds characterized by an excessive scarring due to excessive production, deposition of collagen and extracellular matrix (ECM) molecules.
  • Keloids which are typically rather difficult to cure, are accompanied by itching and discomfort, affecting the patient's physical function and appearance, and may cause psychological disorders.
  • TGF-[3 Transforming Growth Factor beta
  • CGF Connective Tissue Growth Factor
  • CTGF Intra Cellular Adhesion Molecule-1
  • Hair follicles undergo three cycles consisting of anagen, catagen and telogen throughout life. Cyclical hair growth is dependent on epithelial stem cells that reside in the permanent, bulge, region in the hair follicle outer root sheath.
  • hair growth may be unwanted.
  • Various technics exist to remove unwanted hair such as shaving, waxing, chemical depilatory creams and pulsed light. All of these technics have drawbacks. Shaving triggers rashes, razor bumps, nicks and cuts and irritates the skin. Waxing causes pain, discomfort and for some short hairs a limited removal. Depilation affects the part of the hair above the surface of the skin, and can trigger irritancy. Pulsed light allows to remove the part below the skin and is therefore longer-lasting.
  • Dickkopf/Wnt signaling pathway inhibitor 1 is a human gene that encodes for a secreted protein called Dickkopf 1 (DKK1 ) which is involved in embryonic development through its inhibition of the Wnt signaling pathway. Therefore, if inhibiting the hair growth may be of interest, it would be reached through the inhibition of the Wnt signaling pathway.
  • DKK1 Dickkopf 1
  • Jasminum sambac Oleaceae also known as Arabian Jasmine (also called jasmine) is native of Middle East and Asia. Jasminum sambac flowers are characterized by a rather pleasant aroma, used for thousands of years in perfume industry and as flavouring agent in jasmine tea and aromatherapy. Indeed, Jasminum sambac is a perennial plant cultivated by farmers essentially for their flowers for the needs of the tea and perfume industries. In this regard, the leaves are regularly pruned for fostering flowering. Consequently, it generates a large amount of leaves that is typically disposed and discarded. The use of the extract of Jasminum sambac is known in cosmetic field and is typically focused on the flowers thereof.
  • EP-B 2275113 describes a cosmetic preparation containing 3- methyloctano-4-lactone and an extract of the whole part of Jasminum sambac, typically including the flower part, for use in improvement of blood circulation of skin and in elevation of the skin temperature.
  • JP-A 2008031089 relates to plant extracts including such of the entire part of Jasminum sambac for whitening the skin.
  • JP-S 6452709 discloses an extract of the whole part of Jasminum sambac for moisturizing and for softening the skin.
  • KR-B1 -101762314 discloses a mixture of plant extracts including an extract of all part of Jasminum sambac, preferably flowers, for moisturizing the skin.
  • none of these documents discloses extracts that comprise specific iridoid glycosides in the extract of Jasminum sambac or specific cosmetic of therapeutic uses of an extract of Jasminum sambac.
  • the hydroethanolic extract of the leaf of Jasminum sambac was reported to contain sambacoside A and molihuaside A (El-Hawary et al., International Journal of Applied Pharmaceutics, Vol. 11 , Issue 6, 154-164, 2019). This document does not indicate the presence of further molihuasides or a specific cosmetic of therapeutic uses of an extract of Jasminum sambac.
  • composition of an extract of Jasminum sambac is reported to contain sambacosides A, E and F, without teaching specific extraction methods used (Tanahashi T. et al., Tetrahedron Letters, Vol. 29, N°15, pp 1793-1796, 1988). This document does not indicate a specific cosmetic of therapeutic uses of an extract of Jasminum sambac. Methanolic and ethanolic leaf extracts of Jasminum sambac were generally reported (Sultana et al., European Journal of Biomedical and Pharmaceutical Sciences, Vol. 6, Issue 5, 350-358, 2019).
  • Jasminum sambac concentration of the active components in a plant
  • concentration may vary according to the seasons. Furthermore, such concentration also varies according to the organ of the plant. Consequently, it may be for interest to have at disposal an extract of Jasminum sambac exhibiting a stable amount of specific iridoid glycosides content regardless of the seasons.
  • Jasminum sambac that having specific components and usable in cosmetic and/or pharmaceutical fields, particularly in skin care, scalp care and hair care.
  • extract of the leaves of Jasminum sambac comprising at least two sambacosides including sambacoside A and at least two molihuasides bears unexpectedly beneficial properties in skin care, in particular for improving the skin defense against microbial pathogens, for improving the skin barrier function, for improving the skin elasticity, for improving the skin soothing, and for preventing hair growth
  • leaf extract for this purpose, it is surprisingly possible to use the leaves that are typically disposed in jasmine flower production. This enables valorizing by- products issued from the plant Jasminum sambac for satisfying the cosmetic industries.
  • the leaf extract of Jasminum sambac of the present invention may be characterized in having a specific biomarkers content and may satisfy expectations in cosmetic and/or pharmaceutic applications.
  • the present invention relates to an aqueous or hydroalcoholic extract of the leaves of Jasminum sambac comprising iridoid glycosides comprising:
  • a further aspect relates to a method for preparing an extract according to the invention, comprising the steps of: i) crushing the leaves, optionally dried, ii) solid/liquid extraction of the crushed leaves with at least one solvent selected from water, or a mixture of water and alcohol, wherein the alcohol is selected from the group consisting of glycerol, propanediol, methanol, ethanol, propanol, butanol, butylene glycol, propylene glycol, preferably wherein the solvent is a mixture of ethanol/water, a mixture of glycerol/water or a mixture of propanediol/water at the ratio of 95:5 to 5:95, preferably 90:10 to 20:80, more preferably 70:30 to 50:50, a) wherein the solid/liquid extraction being performed for 30 min to 10 hours, preferably for 45 min to 8 hours, more preferably for 1 h to 5 hours, at room temperature, b) wherein the ratio solid/liquid being at 1 :5 to 1 :
  • Another aspect of the present invention concerns a cosmetic or pharmaceutic composition
  • a cosmetic or pharmaceutic composition comprising: - an extract of the leaves of Jasminum sambac according to the present invention as an active ingredient; and
  • composition is a composition for topic use selected from the group consisting of a solution, a suspension, an emulsion, a cream, a paste, a gel, a lotion, a powder, a soap, a surfactant-containing water, an oil, a shampooing, and a spray; and/or wherein the composition is a nutraceutical composition which is administered orally.
  • Another aspect of the invention relates to the use of a composition comprising or consisting of an extract or a cosmetic composition according to the present invention in skin care.
  • the present invention thus relates to a cosmetic use of a composition comprising or consisting of an extract of the leaves of Jasminum sambac in skin care.
  • Another aspect of the invention relates to the use of a composition comprising or consisting of an extract or a cosmetic composition according to the present invention for inhibiting hair growth.
  • the present invention further relates to a cosmetic use of a composition comprising or consisting of an extract of the leaves of Jasminum sambac in hair care.
  • Another aspect of the invention concerns a composition
  • a composition comprising or consisting of an extract of an aqueous or hydroalcoholic extract of the leaves Jasminum sambac (preferably an extract of the present invention) as an active ingredient for use in a method for the treatment or prevention of a skin disorder selected from the group consisting of atopic dermatitis, acne, dandruff, sebum secretion, oily skin, fibrotic disorder, scar, pathologic skin redness, pathologic skin inflammation, and a combination of two or more thereof.
  • a skin disorder selected from the group consisting of atopic dermatitis, acne, dandruff, sebum secretion, oily skin, fibrotic disorder, scar, pathologic skin redness, pathologic skin inflammation, and a combination of two or more thereof.
  • the present invention further relates to a composition
  • a composition comprising or consisting of an aqueous or hydroalcoholic extract of the leaves of Jasminum sambac (preferably an extract of the present invention) as an active ingredient for use in a non-therapeutic method for the management of atopic dermatitis prone skin and acneic prone skin (acne prone skin), for treating and/or limiting fibrotic disorders, for treating or limiting scars, for treating and/or preventing skin redness and skin inflammation, or for two or more thereof.
  • Figure 1 shows the UV-chromatogram of the leaf extract of Jasminum sambac, scanned at 236 nm, according to the invention.
  • Figure 2 shows the evaluation of the Lucifer yellow passage in reconstituted human epidermis (RHE), treated or not with the extract according to the present invention, and infected or not with Malassezia furfur, after 6 hours of contact on the top of RHE.
  • An aspect of the present invention relates to an aqueous or hydroalcoholic extract of the leaves of Jasminum sambac comprising iridoid glycosides comprising:
  • Iridoid glycosides as used in the context of the present invention, including sambacosides and molihuasides, may be understood in the broadest sense as understood in the art.
  • the term “iridoid” may be understood in the broadest sense as generally understood in the art. Preferably, it may include any iridoid-based components including iridoid glycosides.
  • iridoid glycosides examples include El-Hawary et al. (International Journal of Applied Pharmaceutics, Vol. 11 , Issue 6, 154-164, 2019) and Tanahashi T. et al. (Tetrahedron Letters, Vol. 29, N°15, pp 1793-1796, 1988). Further examples and sambacosides such as sambacosides A to G and molihuasides such as molihuasides A to E are known in the art.
  • the core structure (also: basic skeleton) of iridoid glycosides as used in the context of the present invention often may be as follows:
  • a hydrogen atom at carbon atoms 1 , 3 and 5-10 may or may not be optionally substituted by an organic or inorganic residue.
  • Glc may be a saccharide.
  • carbon atom 10 forms an ester group, in particular a methyl ester - CO-O-CH3.
  • the iridoid glycosides content represents at least 5% by weight based on the total weight of the dry matter content of the extract.
  • the iridoid glycosides content may represent between 5 to 30% by weight, more preferably 7 to 28% by weight, in particular 8 to 25% by weight, based on the total weight of the dry matter content of the extract.
  • the extract further comprises at least two sambacosides selected from sambacosides E or F, or a mixture thereof; and the molihuasides are selected from molihuasides A, B, C, D and E, or a mixture of two or more thereof.
  • the sambacosides may be a mixture of sambacosides A, E and F, and wherein the molihuasides may be a mixture of molihuasides A to E.
  • the extract comprises sambacosides A, E and F, and the molihuasides are molihuasides A to E.
  • sambacoside A may represent 30 to 70%, preferably 35 to 65%, even more preferably 40 to 60% by weight, based on the total weight of total iridoid glycosides.
  • the extract comprises 1 to 70% by weight, preferably 10 to 60% by weight, based on the total weight of the dry matter content of the extract, of molihuasides.
  • the total iridoid glycosides content may represent at least 5% by weight based on the total weight of the dry matter content of the extract.
  • the total iridoids content in the leaf extract of Jasminum sambac according to the present invention may represent 1000 to 3000 ppm, preferably 1500 to 2500 ppm, more preferably 1800 to 2200 ppm, expressed in equivalent oleuropein.
  • the leaf extract of Jasminum sambac according to the present invention may contain less than 0,001 % by weight, preferably less than 0,0001 % by weight based on the total weight of the dry matter content of the extract, of tannins and sambacin.
  • the leaf extract of Jasminum sambac according to the present invention may contain neither tannins nor sambacin.
  • the leaf of Jasminum sambac contains a pool of active molecules among which polyphenols and iridoids glycosides.
  • Iridoids are a type of monoterpenoids found in wide variety of plants.
  • Iridoids glycosides also called oligomeric iridodial glycosides, namely sambacosides and molihuasides, have been reported to be present in leaf of Jasminum sambac.
  • extract may be any substance made by extracting the leaves of Jasminum sambac.
  • the extract of Jasminum sambac may be a solvent-based extract obtained by means of solid/liquid extraction method, generally called maceration extraction or lixiviation extraction.
  • extracting may be achieved by using at least one solvent, preferably a polar solvent.
  • the extract may be obtained from aqueous, alcohol or hydroalcoholic extraction methods including cold or hot extraction, ultrasonic extraction, reflux cooling, and microwaves extraction, this later may be performed by using water as extraction solvent.
  • extract means the extract of the leaves of Jasminum sambac.
  • the extract is obtainable (or obtained) by solid/liquid extraction of the leaves of Jasminum sambac in a solvent selected from water, or a mixture of water and alcohol wherein alcohol being methanol, ethanol, propanol, butanol, glycerol, butylene glycol, propylene glycol, propanediol, preferably ethanol/water, glycerol/water or propanediol/water.
  • a solvent selected from water, or a mixture of water and alcohol wherein alcohol being methanol, ethanol, propanol, butanol, glycerol, butylene glycol, propylene glycol, propanediol, preferably ethanol/water, glycerol/water or propanediol/water.
  • the extract is obtainable (or obtained) by solid/liquid extraction of the leaves of Jasminum sambac in a solvent selected from water, or a mixture of water and alcohol, wherein the alcohol is selected from the group consisting of glycerol, propanediol, methanol, ethanol, propanol, butanol, butylene glycol, propylene glycol, and a combination of two or more thereof, preferably wherein the solvent is a mixture of ethanol/water, glycerol/water or a mixture of propanediol/water.
  • hydroalcoholic may be understood in the broadest sense as generally understood in the art. It may be any composition comprising one or more alcohols and water.
  • a hydroalcoholic extraction solvent may be any alcohol/water mixture.
  • the hydroalcoholic extraction solvent may be ethanol/water, glycerol/water or propanediol/water.
  • the extract of the invention is obtained by extracting the leaves of Jasminum sambac with ethanol/water, glycerol/water or propanediol/water.
  • the extract of leaves according to the invention may be an hydroalcoholic extract, wherein the ratio of water/alcohol being 5:95 (v/v), preferably 10:90 (v/v), more preferably 20/80 (v/v), in particular 30:70 (v/v).
  • the dry matter content of the extract represents 5 g/L to 15 g/L preferably 7 g/L to 13 g/L, more preferably 8.5 g/L to 12 g/L (weight/volume of solvent), respectively 0.5% to 1.5%, preferably 0.7% to 1.3%, more preferably 0.85% to 1 .2% by weight over the total weight of the extract.
  • the extract according to the present invention may be liquid, pasty or solid at standard conditions (room temperature of approximately 20°C, normal pressure of approximately 1013 hPa).
  • the terms “liquid” and “fluid” may be understood interchangeably.
  • the extract is first obtained in liquid form.
  • the one or more solvents may optionally be removed to obtain a solid form of the extract.
  • a liquid extract i.e., solvent-based extract
  • the extract may be dried.
  • parts of the one or more solvents are removed.
  • a liquid or pasty extract may be obtained.
  • the extract may also be re-diluted with one or more solvents for obtaining a solventbased extract.
  • the extract may also be purified by any means (e.g., crystallization, chromatographic means, etc.).
  • an extract may be optionally designated as “tincture” or “absolute”.
  • the solvent used for the preparation of the solvent-based extract may be an aqueous solvent (water or a buffer), or it may be a combination of an aqueous solvent and a liquid organic solvent.
  • the extract of the leaves of Jasminum sambac according to the present invention is a solvent-based extract wherein the dilution solvent may be selected from water, aqueous buffer, alcohols, glycols, or a mixture thereof.
  • the alcohols may be preferably selected from methanol, ethanol, propanol, butanol, glycerol, butylene glycol, propylene glycol, propanediol, or a mixture of two or more thereof.
  • the extract of the leaves of Jasminum sambac according to the invention may be an aqueous-based extract.
  • the extract of the leaves of Jasminum sambac according to the invention may be obtained by extracting with a mixture of glycerol/water at a volume ratio from 95/5 to 5/95, preferably from 90/10 to 70/30 or 80/20 to 20/80.
  • the extract of the leaves of Jasminum sambac according to the invention may be obtained by extracting with a mixture of ethanol/water or propanediol/water at a volume ratio from 95/5 to 5/95, preferably from 40/60 to 60/40 or 70/30 to 50/50.
  • the mixtures of glycerol/water and propanediol/water may stabilize the product against alteration by microbial growth, so that no additional preservative is necessary.
  • the extract of the leaves of Jasminum sambac may be optionally obtained in a fraction produced by conducting other purification known methods including separation through an ultrafiltration membrane with a constant molecular weight cutoff value, or separation through various chromatographic methods, or liquid-liquid separation or crystallization or precipitation.
  • dry matter may be understood in the broadest sense as an extract according to the present invention as dry material, i.e., without the solvent. In the calculation, the mass of the solvent is mathematically subtracted from the total mass.
  • the dry matter in physical form may be obtained by a suitable extraction method, followed by a step of drying the extract obtained.
  • the drying may be performed by any method suitable for this purpose known in the art. Drying means removing the one or more solvents used for extraction.
  • a method for preparing an extract according to the invention comprising the steps of: i) crushing the leaves, optionally dried, ii) solid/liquid extraction of the crushed leaves with at least one solvent selected from water, or a mixture of water and alcohol, wherein the alcohol is selected from the group consisting of glycerol, propanediol, methanol, ethanol, propanol, butanol, butylene glycol, propylene glycol, preferably wherein the solvent is a mixture of ethanol/water, a mixture of glycerol/water or a mixture of propanediol/water at the ratio of 95:5 to 5:95, preferably 90:10 to 20:80, more preferably 70:30 to 50:50, a) wherein the solid/liquid extraction being performed for 30 min to 10 hours, preferably for 45 min to 8 hours, more preferably for 1 h to 5 hours, at room temperature, b) wherein the ratio solid/liquid being at 1 :5 to 1 :20, preferably at 1 :
  • step iv) optionally, concentrating the liquid part containing the solvent-based extract by removing at least partly the extraction solvent. It will be understood that the extract obtained after the solid/liquid extraction in step ii) may exhibit the biological activities as laid out if the experimental parts of the present application.
  • the method may comprise a step ii’) of repeating the step ii).
  • repeating may be once to 3 times, thus, 1 , 2 or 3 times
  • the solid/liquid extraction may be performed at 15 to 120°C, preferably at 15 to 110°C, even more preferably at 18 to 100°C, particularly at 20 to 100°C for 30 minutes to 72 hours, preferably for 45 minutes to 60 hours, more preferably for 1 hour to 55 hours, most preferably for 2 to 48 hours.
  • separating solid phase and liquid phase for recovering the liquid part may be conducted by any means known in the art such as centrifugation, decantation, or filtration.
  • the solvent-based extract may be further dried by any means known in the art such as spray-drying.
  • the concentrated extract may be further resolubilized in a suitable cosmetic solvent selected from the group consisting of polyols, glycols, esters, and a mixture of water with one thereof.
  • suitable cosmetic solvents may be glycerol, propanediol, butylene glycol, propylene glycol, ethyl acetate.
  • the ratio of the plant material to the extraction solvent may be comprised between 1/5 and 1/50, preferably between 1/10 and 1/20 by weight.
  • the extract is preferably either dried, or frozen or freeze-dried, or fresh.
  • the plant material may be used in any form such as, e.g., as powder, crushed or any other form.
  • the extract according to the present invention may be obtained by a commercial supplier or may be prepared from the leaves of Jasminum sambac as described above.
  • the hydroalcoholic solvent may be a solvent mixture that is mainly composed of one or more alcohols and water.
  • the hydroalcoholic solvent may contain between 1 and 99% (v/v) alcohol, or between 5 and 95% (v/v) alcohol, or between 10 and 90% (v/v) alcohol, or between 15 and 85% (v/v) alcohol, or between 20 and 80% (v/v) alcohol, or between 25 and 75%, or between 30 and 70% (v/v) alcohol, or between 40 and 60% (v/v) alcohol, or approximately 50% (v/v) alcohol.
  • water may also include hot water or subcritical water.
  • one or more aqueous buffers may be used.
  • an aspect of the present invention refers to an extract of the leaves of Jasminum sambac obtainable (or obtained) by implementation of the preparation method as described above.
  • the invention relates to the cosmetic use of a composition comprising or consisting of an extract of the leaves of Jasminum sambac or a cosmetic composition comprising such extract in skin care.
  • An aspect of the present invention relates to the use of a composition comprising or consisting of an extract or a cosmetic composition according to the present invention in skin care.
  • a cosmetic preferably non-therapeutic use
  • a therapeutic use can also be a therapeutic use.
  • the present invention relates to an extract or a cosmetic composition according to the present invention for use in a method in skin care.
  • the term “skin care” may be understood in the broadest sense. Preferably, it may include improving the skin defense against microbial pathogens, for preventing the skin dysbiosis, for preserving or restoring the skin symbiosis, for improving and/or restoring the skin barrier function, for preventing formation of stretch-marks, for preventing and/or regulating the sebum secretion, for preventing the oily appearance of the hair and/or skin, or for two or more thereof.
  • the extract of the present invention or a cosmetic composition comprising such extract may be used as an anti-dandruff agent.
  • skin care is for managing skin prone to atopic dermatitis, for preventing acne, for limiting fibrotic disorders, for limiting scarring, for preventing inflammation and/or redness, or a combination of two or more thereof.
  • skin care is for preventing or decreasing of irritation of the skin.
  • the extract of the present invention or a cosmetic composition comprising such extract may be used as an antioxidant agent.
  • the extract of the present invention or a cosmetic composition comprising such extract may be used as a whitening agent.
  • the present invention relates to an extract or a cosmetic composition according to the present invention for use in a method for preventing or decreasing of irritation of the skin.
  • skin care is preventing or decreasing of irritation of the skin comprising at least one of the following: reducing inflammation of the skin and/or soothing of the skin; stimulating skin’s intrinsic antimicrobial defense mechanisms.
  • skin care comprises the following effects: improving and/or restoring the skin barrier function and/or skin hydration, improving skin elasticity, stimulating skin’s intrinsic antimicrobial defense mechanisms, preventing the skin dysbiosis, preserving or restoring the skin symbiosis, reducing inflammation of the skin and/or soothing of the skin, reducing fibrosis, in particular when associate with formation of scars, preventing formation of stretch-marks, for preventing and/or regulating the sebum secretion, for preventing the oily appearance of the skin, or a combination of two or more thereof.
  • skin care is skin care is for reducing quantity and/or intensity of reddish skin lesions.
  • skin care may further be for preventing acne vulgaris, for improving or restoring the skin aspect, or a combination thereof.
  • skin care may further be for improving the skin hydration, for improving the skin comfort, for improving and/or restoring the skin elasticity, for preventing formation of stretch-marks, for improving and/or restoring the skin soothing, or for two or more thereof.
  • a further aspect relates to the use of a composition comprising or consisting of an extract or a cosmetic composition according to the present invention for inhibiting hair growth.
  • a cosmetic preferably non-therapeutic use
  • a therapeutic use can also be a therapeutic use.
  • the present invention relates to an extract or a cosmetic composition according to the present invention for use in a method for inhibiting hair growth, for preventing the oily appearance of the hair.
  • the invention further concerns a composition
  • a composition comprising or consisting of an extract of the leaves of Jasminum sambac as an active ingredient for use in a non- therapeutic method for the management of atopic dermatitis prone skin and acneic prone skin, for treating and/or limiting fibrotic disorders or conditions, for treating and/or limiting scars, for treating and/or preventing skin redness and skin inflammation, or for two or more thereof.
  • management may be understood in the broadest sense as means to limit, to reduce the risk of developping atopic dermatitis and/or acneic prone skin, and to improve atopic dermatis and acneic skin phenotype (acne).
  • atopic dermatitis prone skin and “skin prone to atopic dermatitis” is a skin type which has a propensy to develop inflammatory and pruritic skin lesions. It does not refer to skins suffering from a skin disease but can trigger to atopic dermatitis when non treated.
  • an acne prone skin and “skin prone to acneic lesions” may be understood in the broadest sense as a skin type which has a propensy to developcomedones and inflammatory lesions.
  • Acne prone skin does not refer to skin suffering from a skin disease but can trigger to acne vulgaris when non treated.
  • Both atopic dermatitis and acne lesion preferably refer to inflamed and inflammatory lesions, preferably associated with atopic dermatitis (redness) and acne vulgaris (redness, comedones, pustules and papules).
  • the extract of the present invention is capable to regulate the connective tissue abnormalities to its inflammatory origin, to improve skin itching and discomfort often reported in these diseases by reduction the skin pain and by improving the skin elasticity.
  • experimental results demonstrated that the extract according to the present invention is anbling to decreas CTGF expression and to reduce the associated collagen synthesis. Since CTGF plays a central role in the development and maintenance of the fibrotic response, the extract according to the invention represents a potential strategy to treat keloids and other fibrotic disorders or conditions.
  • the extract according to the invention is able to induce MMP-1 and MMP-3 expression leading to the decrease of protein levels of collagens, thus reversing the pro-fibrotic phenotype of fibrotic fibroblasts found in keloids, hypertrophic scars and scleroderma.
  • the terms “subject” and “individual” may be understood in the broadest sense as any living being.
  • a subject preferably is a human or (non-human) animal, more preferably a human or (non-human) mammal, in particular a human being.
  • a subject may also be designated as “patient”.
  • subject suffering or will suffer e.g., via a surgical procedure, a wound that may result in scar formation such as keloids and hypertrophic scars and/or a fibrotic disorder or condition, or has resulted in scar formation such as keloids and hypertrophic scars and/or a fibrotic disorder or condition.
  • wound may be understood in the broadest sense as injuries to the skin and subcutaneous tissue. Such wounds may include lacerations, bums, punctures, trauma, bites, fistulas, ulcers, lesions caused by infections, surgical wounds, incisional wounds, contractures after burns, and wounds resulting from cosmetic surgical procedures.
  • keloid may be understood in the broadest sense as a scar that results in an overgrowth of tissue at the site of a healed skin injury. Keloids are usually accompanied by severe itchiness, pain and changes in texture. In severe cases, it may affect movement of skin.
  • reducing scar formation and “managing scarring” may be understood in the broadest sense. Preferably, it may be understood as any decrease or condition in keloid or hypertrophic scar formation that provides a therapeutic or cosmetic benefit, for example, by decreasing the size and/or depth of a keloid or hypertrophic scar relative to keloid or hypertrophic scar formation or by reducing the size of an existing keloid or hypertrophic scar to a subject.
  • fibrotic disorders or conditions may be those associated with TGF-[3-induced CTGF expression, including but not limited to tissue fibrosis.
  • fibrotic disorders or conditions and/or scars may be keloids and hypertrophic scars are those with elevated levels of one or more of the following biomarkers : CTGF expression, collagen type I (COL1A1 ), fibulin-5 (FBLN5), fibromodullin (FMOD).
  • CTGF expression collagen type I (COL1A1 )
  • FBLN5 fibulin-5
  • FMOD fibromodullin
  • the terms “treating” and “managing” may be understood in the broadest sense as a means accomplishing one or more of the following: (a) reducing the severity of the disorder or condition; (b) limiting or preventing development of symptoms characteristic of the disorder or condition being treated; (c) inhibiting worsening of symptoms characteristic of the disorder or condition being treated; (d) limiting or preventing recurrence of the disorder or condition in patients that have previously had the disorder or condition; and (e) limiting or preventing recurrence of symptoms in subject that was previously symptomatic for the disorder(s) or condition(s).
  • limiting and “reduding” may be understood in the broadest sense as means to limit the disorder or condition in subject at risk of developing the disorder or condition.
  • Another aspect of the present invention relates to a cosmetic or a pharmaceutical composition
  • a cosmetic or a pharmaceutical composition comprising:
  • composition is a composition for topical use selected from the group consisting of a solution, a suspension, an emulsion, a cream, a paste, a gel, a lotion, a serum, a powder, a soap, a surfactant-containing water, an oil, a shampooing, and a spray, or wherein the composition is a nutraceutical composition which is administered orally
  • the extract according to the invention may optionally be considered as an (or optionally even the sole) active ingredient.
  • active ingredient may be understood in the broadest sense as a component that may exhibit a desired and intended activity, either alone or together with one or more other ingredients such as one or more carriers that are themselves inactive or another active ingredient that may optionally act synergistically.
  • the cosmetic or pharmaceutic composition may be used for any purpose and in any form.
  • the composition is a composition for topic use selected from the group consisting of a solution, a suspension, an emulsion, a cream, a paste, a gel, a lotion, a serum, a powder, a soap, a surfactant-containing water, an oil, a shampooing, and a spray, or wherein the composition is a nutraceutical composition which is administered orally.
  • composition may also be or may be comprised in a product selected from the group consisting of emulsions, gels, ointments, tonics, liquid soaps, bar soaps, bath oils, shower oils, massage oils, makeups, scalp treatments, aftershaves, shaving products, deodorants, shower gel, shampoos, and combinations of two or more thereof.
  • a cosmetic or pharmaceutical composition may also be a nutraceutical composition which can be administered orally to a subject. Then, the cosmetic or pharmaceutical composition may optionally be included in a food product, such as a food supplement. Then, the composition may typically have a systemic effect.
  • a nutraceutical composition according to the present invention may be formulated, with acceptable carriers, in any form suitable for oral administration such as, e.g., tablets, capsules, granules, powder, solution, emulsion, or suspension.
  • the cosmetic or pharmaceutic composition may comprise the extract of the present invention in any content.
  • the composition comprises less than 15% by weight, referred to the total weight of the composition, of an extract according to the present invention.
  • the composition comprises 0.0001 to 10% by weight, more preferably 0.001 to 8% by weight, even more preferably 0.01 to 5% by weight, referred to the total weight of the composition, of the extract according to the present invention.
  • the at least one further cosmetically and/or pharmaceutically acceptable ingredient other than the extract of the invention may be any cosmetically and/or pharmaceutically acceptable ingredient.
  • the cosmetically and/or pharmaceutically acceptable ingredient is or comprises at least one cosmetically and/or pharmaceutically acceptable carrier.
  • the terms “pharmaceutically acceptable carrier”, “pharmaceutically acceptable excipient”, “cosmetically acceptable carrier”, “cosmetically acceptable excipient”, “carrier” and “excipient” may be understood interchangeably in the broadest sense as any substance that may support the cosmetic and/or pharmacological acceptance or usability of the composition according to the present invention containing the extract of Jasminum sambac.
  • the extract of Jasminum sambac nor a composition containing such at least one extract according to the present invention is toxic when applied to the tissue.
  • the composition ready to use preferably may be a liquid formulation, in particular a composition suitable for topic and oral administration.
  • the storage form of the composition may also be liquid (i.e. , solvent-based extract), but may also be a dried form (e.g., a powder such as a powder comprising or consisting of an extract of Jasminum sambac or may be a paste or syrup or the like.
  • a dried form, paste or syrup may be dissolved or emulsified prior to being administered to the skin of interest.
  • a cosmetically and/or pharmaceutically acceptable carrier may exemplarily be selected from the list consisting of an aqueous buffer, saline, water, alcohols, vegetable oils, mineral oils, polymers, or combination of two or more thereof.
  • a cosmetically and/or pharmaceutically acceptable carrier may contain one or more cosmetically and/or pharmaceutically acceptable additives.
  • such cosmetically and/or pharmaceutically acceptable additives may be selected from the group consisting of fragrances/perfumes, dyes, pigments, emulsifiers, lubricants, chelating agents, acidity regulators, antimicrobial agents, preservatives, antioxidants, and combinations of two or more thereof.
  • composition of the present invention may contain, in addition to the extract of Jasminum sambac, one or more other active ingredients.
  • the composition according to the present invention may be cosmetic product or may be comprised in a cosmetic product.
  • the composition may be for any use. Any administration routes are suitable that lead to the desired purpose as claimed. Administration may be local or systemic administration. Administration may be topic administration, transdermal administration, oral administration, administration by mean of injection. In a preferred embodiment, the composition is a composition for topic use. In a preferred embodiment, the composition is a composition for topic use which is administered topically to a subject. In a preferred embodiment, the composition is a composition for topic use which is administered topically to a part of the skin such as, e.g., to the face, scalp, or any part of a body.
  • the present invention may also be used in vitro, ex vivo or in vivo for: reducing inflammation; stimulating intrinsic antimicrobial defense mechanisms; reducing fibrosis; inhibiting hair growth; improving skin barrier function; soothing of skin; skin hydration; and/or skin elasticity.
  • the present invention may also be used in an in vitro cell culture or tissue model for: reducing inflammation; stimulating intrinsic antimicrobial defense mechanisms; and/or reducing fibrosis.
  • the present invention may also be used in vitro, ex vivo or in vivo, in particular in an in vitro cell culture or tissue model, for: increasing expression of one or more polypeptides associated with antimicrobial defense mechanisms such as, e.g., Human Beta Defensin (e.g., Human Beta Defensin 1 , Human Beta Defensin 2 and Human Beta Defensin 3) and/or psoriasin S100A7, Cathelicidin antimicrobial peptide (CAMP), RNase7; decreasing expression of one or more polypeptides associated with inflammatory processes such as e.g., Interleukin-1 (IL-1 ), Interleukin-17 (IL-17), Tumor Necrosis Factor (TNF), Bleomycin Hydrolase (BLMH), and/or cholesterol 25 hydrolase (CH25H); increasing expression of one or more polypeptides associated with skin barrier function such as, e.g., corneodesmosin (CDSN), keratin 1 (KRT1
  • the extract of Jasminum sambac or the composition of the present invention may be used for any purpose. Preferably, it is used for a cosmetic and/or pharmaceutical purposes.
  • a further aspect referred to a composition
  • a composition comprising or consisting of an aqueous or hydroalcoholic extract of the leaves of Jasminum sambac, preferably an extract according to the present invention, as an active ingredient for use in a method for the treatment or prevention of a skin disorder selected from the group consisting of atopic dermatitis, acne, fibrotic disorder, scar, pathologic skin redness, pathologic skin inflammation, dandruff, and a combination of two or more thereof.
  • the present invention also relates to a method of treatment or prevention of a skin disorder selected from the group consisting of atopic dermatitis, acne, fibrotic disorder, scar, pathologic skin redness, pathologic skin inflammation, and a combination of two or more thereof, said method comprising administering a sufficient amount of a composition comprising or consisting of an extract of leaves of Jasminum sambac, preferably an extract according to the present invention, as an active ingredient, to a subject in need thereof.
  • atopic dermatitis may be such as classified as L20 in the 10 th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10).
  • ICD-10 International Statistical Classification of Diseases and Related Health Problems
  • atopic dermatitis may be such as classified as L70 in the ICD-10.
  • scar formation and fibrosis may be such as classified as L90.5 in the ICD-10.
  • pathologic skin redness may be an erythema such as classified as L51-L54 in the ICD-10.
  • the extract of the present invention or a composition comprising such extract may have a local and/or a systemic effect.
  • it when administered locally and/or topically, it (mainly or completely) has a local effect.
  • disorder or “condition” may be understood in the broadest sense as any pathological condition. In a therapeutic context, it may also be designated as a disease. It may preferably be an inherent disease. As used herein, the term “damage” may be understood in the broadest sense as any perturbation or dysfunction in a tissue, particularly in (otherwise) healthy tissue.
  • a skin disorder is a disorder of the skin.
  • the mobile phase system including acetonitrile with 0.1 % formic acid (A) and water with 0.1 % formic acid (B) was performed by gradient elution as follows: 2% (B) from 0- 2min, 2-10% (B) from 2-2.10 min, 10-28% (B) from 2.10-19 min, 28-100% (B) from 19-19.5 min, 100% (B) 19.5-21 .5, 2% (B) at 21 .6 min until 23 min.
  • the sample was injected 5pL for analysis. UV spectra were recorded at 236 nm.
  • the flow rate was set at 0.5mL/min.
  • the ESI-MS spectra were acquired in both negative and positive ion modes and the mass range was ser from m/z 150 to 1500.
  • the sample cone voltage was set at 30 Volts.
  • the collision energy of dissociation was set at 15, 25 and 35 eV in MS/MS analysis.
  • the dry matter content of the leaf extract of Jasminum sambac extracted with glycerol/water represents 7 g/L.
  • Jasminum sambac Leaves of Jasminum sambac were prepared according to example 1 . Solid/liquid extraction were conducted by using propanediol/water at 50/50 (v/v), or ethanol/water at 70/30 (v/v). For this later, the hydroethanolic extract was concentrated by evaporating ethanol under reduced pressure. The concentrated extract was resolubilized in propanediol/water 80/20 (v/v) and further filtered. This filtered extract of Jasminum sambac (hereinafter JSE) was used for the following experiments.
  • JSE This filtered extract of Jasminum sambac
  • the dry matter content of the leaf extract of Jasminum sambac extracted with ethanol/water 70/30 represents between 8 to 11 g/L.
  • Jasminum sambac having the characteristics, meaning comprising at least two sambacosides including sambacoside A and at least two molihuasides (data not shown).
  • mRNA expression was quantified after 24h of NHDF or NHEK treatment with JSE tested at 0.25% by weight.
  • mRNA extraction was realized according to the provider recommendations (Qiagen). Briefly, lysis buffer RLT-Plus was added on the cell pellet and the homogenous lysate was transferred in a “RNeasy” column. The column was washed with buffer. Elution was realized with RNase-free water and the RNA quantitation was done by O.D at 260 nm, 280 nm, and 320 nm measurements (Biotek, Cytation3 & Take3 Plate) with “Nucleic Acid Quantification” software application. mRNA quality was checked using a fragment analyzer (Advanced Analytical).
  • mRNA reverse transcription allowing the obtention of cDNA templates was performed on a thermal cycler (Bio-Rad).
  • cDNA templates were used to perform the qPCR.
  • the transcriptom ic study it was used a predesigned plates (Bio-Rad) for ECM components, skin barrier function, epidermal differentiation, inflammation, hydration and skin homeostasis.
  • the data generated allowed the automatic calculation using Bio-Rad CFX manager of mRNA expression fold change and p-values in comparison to untreated condition. All data were statistically significant compared to control condition with a threshold for the p- value ⁇ 0.1
  • Table 1 Comparison of the relative gene expression ratio between the control group and the group treated by JSE. Genes related to antimicrobial defenses mechanisms.
  • Table 2 Comparison of the relative gene expression ratio between the control group and the group treated by JSE. Genes related to inflammatory process.
  • Table 3 Comparison of the relative gene expression ratio between the control group and the group treated by JSE. Genes related to skin barrier function and epidermal differentiation process.
  • Table 4 Comparison of the relative gene expression ratio between the control group and the group treated by JSE. Genes related to hydration properties.
  • Table 5 Comparison of the relative gene expression ratio between the control group and the group treated by JSE. Genes related to dermis remodeling, connective tissue formation and skin elasticity. control group and the group treated by JSE.
  • Table 7 Comparison of the relative gene expression ratio for DKK1 between the control group and the group treated by JSE. Stimulation of skin’s intrinsic antimicrobial defense mechanisms
  • Table 1 shows, in NHEK, the ability of JSE to protect the skin against pathogen microbial through the induction of the expression of endogenous antimicrobial peptides.
  • the table 1 is a result comparison of the relative gene expression ratio of antimicrobial peptide genes between the control group and the group treated by JSE.
  • the set of the modulated genes comprises DEFB4A, DEFB103B and S100A7 coding respectively for the antimicrobial peptides hBD2 and hBD3 and psoriasin.
  • JSE significantly modulates the expression of h
  • JSE can protect the skin against pathogens colonization.
  • the stimulation of the expression of these antimicrobial peptides is known to bring beneficial effect for symbiotic skins i.e. , healthy skin and for dysbiosis skins i.e. , non-healthy skins.
  • Table 2 demonstrates, in NEHK, the anti-inflammatory properties of JSE as it allows a significant inhibition of the mRNA expression of several pro-inflammatory markers (IL1 , TNF, CH25H).
  • IL1 pro-inflammatory markers
  • TNF tumor necrosis factor
  • CH25H pro-inflammatory markers
  • - IL1 as a master regulator of inflammation via controlling a variety of innate immune processes, is known to often play a role in health and disease.
  • TNF is involved in the regulation of immune cells. TNF is released in response to bacterial products such as lipopolysaccharides but also in response to IL1. Also, TNF promotes the inflammatory response, which, in turn, causes many diseases such as psoriasis, atopic dermatitis, acne.
  • JSE induces an up regulation of BLMH.
  • BLMH is known to regulate the secretion of chemokines involved in inflammation and wound healing. Indeed, when BLMH is down regulated, the skin infammation increases.
  • JSE exhibits an anti-inflammatory effect which could be beneficial to sooth inflammatory skin such as acneic skin (acne), atopic dermatitis skin, psoriatic skin or eythematous skin.
  • Table 3 demonstrates, in NHEK, the ability of JSE to improve the skin barrier function by upregulating the expression of differentiation genes and an enzymes involved in ceramide metabolism and in autophagy process (SMPD1 ). Indeed, JSE induces an overexpression of CDSN, KRT1 , TRPV4 and SMPD1 :
  • a cation channel activated by hypotonicity, moderate heat, or shear stress is necessary for the correct establishment of tight junctions and as well as the regulation of both the barrier function of tight junctions.
  • - SMPD1 an enzyme that breaks down sphingomyelin into ceramide and phosphorylcholine, ceramides are key on lysosomal biogenesis. Lysosome is known to often play a role in epidermal homeostasis.
  • JSE can preserve and reinforce the skin barrier function. Indeed, JSE induces a statistically significant overexpresion of several proteins of interest for the epidermal differentiation process a major biological process responible for skin barrier function maintenance.
  • Table 4 shows, in NHEK, the ability of JSE to improve the skin hydration. Indeed, the expression of the genes AGPAT9, BLMH, HAL, XYLT1 and CSPG4 was statistically significantly upregulated in cells treated by JSE.
  • AGPAT9 is an enzyme participates in glycerolipid and glycerophospholipid metabolisms. This later serves as a source of free fatty acids that are known to often be involved in the maintenance of epidermal permeability barrier function.
  • BLMH is a protease involved in the degradation of citrullinated filaggrin monomers into free amino acids of interest for skin hydration.
  • the expression and activity of BLMH was shown to be reduced in patients suffering from atopic dermatitis and psoriasis.
  • - XYLT 1 is an enzyme catalyzes the transfer of UDP-xylose to serine residues. Addition of this xylose to the core protein is required for the biosynthesis of the glycosaminoglycan chains characteristic of proteoglycans.
  • - CSPG4 is a cell surface proteoglycan that binds, among, to perlecan another proteoglycan.
  • Table 5 shows, in NHDF, the ability of the JSE to improve fibrotic skin by regulating the expression of genes involved in connective tissue formation and its degradation.
  • JSE can act as an anti-fibrotic agent to improve healing outcome of fibrotic scars such as hypertrophic and keloids scarring.
  • JSE stimulated the expression of elastin, allowing a better comfort of the skin.
  • the stimulation of elastin expression in cicatricial skin will render the skin more supple thus restoring a better skin sensation and comfort.
  • cicatricial skin suffers of rigidity associated with a loss of skin comfort.
  • Table 6 shows, in NHEK, the ability of JSE to sooth the skin. Indeed a statistically significant down regulation of TRPV1 mRNA expression was observed in keratinocytes treated with JSE. The result evidenced that JSE has soothing properties. This property could be useful for sensitive and itchy skins. Moreover, JSE can be also beneficialal for dry skin known to be rather reactive and painful. The inhibition of TRPV1 could be also of interest for atopic skins and psoriatic skins.
  • Table 7 shows, in NHEK, the ability of JSE to inhibit hair growth. Indeed a statistically significant upregulation of DKK1 mRNA expression was observed in keratinocytes treated by JSE. As DKK1 is an inhibitor of Wnt pathway, which is a major biological pathway involve in hair growth cycle, it could be assumed that JSE is able to reduce the hair growth.
  • RNA expression evaluated by RTqPCR assays were further realized on reconstructed human epidermis (RHE) infected or not by Malassezia furfur, treated or not with JSE at concentration of 0.25% by weight.
  • RHE is a well known model which mimics human epidermis behavior.
  • the preparation methods (RTqPCR) are similar as those described in Example 3.
  • results obtained on RHE confirmed those obtained on isolated skin cells as discussed in Example 3, table 1. Indeed, JSE enhances the ability of the skin to induce the expression of genes antimicrobial defense after infection of the skin by Malassezia furfur as shown below:
  • Table 8 Comparison of the relative gene expression ratio between the Malassezia furfur infected control group and the group treated by JSE. Genes related to antimicrobial defenses mechanisms.
  • Table 8 demonstrates and confirms, in RHE, the ability of JSE to protect the skin against Malassezia furfur through the induction of the expression of endogenous antimicrobial peptides. Surprisingly, JSE has no direct inhibition activity against Malassezia furfur. In addition, the table 8 highlights that JSE enables to induce, in RHE, the synthesis of antimicrobial peptides compared to table 1. Indeed, CAMP, hBD1 , and RNase7 are also modulated. CAMP is a peptide cleaved into the LL-37 active form having a broad spectrum of antimicrobial activity. RNase7 exhibited a potent ribonuclease activity on human skin. RNase7 has a broad-spectrum antimicrobial activity. The stimulation of the expression of these antimicrobial peptides is known to bring beneficial effect such as for preventing dandruff formation on the scalp, for soothing the scalp, more generally for maintaining the skin and scalp healthy.
  • Results obtained on RHE also confirmed those obtained on isolated skin cells as discussed in Example 3, table 2. Indeed, JSE enhances the ability of the skin to inhibit the expression of inflammatory genes after colonization of the skin by Malassezia furfur as shown below:
  • Table 9 Comparison of the relative gene expression ratio between the Malassezia furfur infected control group and the group treated by JSE. Genes related to inflammatory process.
  • JSE exhibits an anti-inflammatory properties as it allows a significant inhibition of the mRNA expression of several pro-inflammatory markers (IL-1 , TNF, IL-17). Therefore, JSE enables to sooth the skin.
  • Results obtained on RHE are in line with those obtained on isolated skin cells in Example 3, table 3 and confirm the ability of JSE in restoring and/or maintaining the epidermis barrier function of the skin.

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Abstract

La présente invention concerne un extrait des feuilles de Jasminum sambac renfermant des glycosides iridoïdes comprenant du sambacoside A et au moins deux molihuasides, une composition contenant un tel extrait et ses utilisations. En outre, la présente invention concerne une composition cosmétique ou pharmaceutique comprenant un tel extrait en tant que principe actif pour la peau et pour inhiber la pousse des poils.
PCT/EP2023/065787 2022-07-11 2023-06-13 Composition comprenant un extrait de jasminum sambac et son utilisation WO2024012787A1 (fr)

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