WO2024074633A1 - Alcoholic extract of white lily flowers lilium candidum l, method for obtaining same, and cosmetic composition containing same - Google Patents

Alcoholic extract of white lily flowers lilium candidum l, method for obtaining same, and cosmetic composition containing same Download PDF

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Publication number
WO2024074633A1
WO2024074633A1 PCT/EP2023/077617 EP2023077617W WO2024074633A1 WO 2024074633 A1 WO2024074633 A1 WO 2024074633A1 EP 2023077617 W EP2023077617 W EP 2023077617W WO 2024074633 A1 WO2024074633 A1 WO 2024074633A1
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weight
flowers
extract
white lily
lily flowers
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PCT/EP2023/077617
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French (fr)
Inventor
David Legangneux
Maéva GILLET
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Chanel Parfums Beaute
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Publication of WO2024074633A1 publication Critical patent/WO2024074633A1/en

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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]
    • A61K8/9794—Liliopsida [monocotyledons]
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • 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
    • A61Q19/08—Anti-ageing preparations
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • A61K2800/522—Antioxidants; Radical scavengers

Definitions

  • the invention relates to an extract of white lily flowers, Lilium candidum L., its process for obtaining it, a cosmetic composition containing it, as well as different cosmetic uses.
  • the skin is mainly made up of three layers, namely, starting from the most superficial, the epidermis, the dermis and the hypodermis.
  • the epidermis largely contributes to protecting the skin and maintaining its proper functioning.
  • Aging and photoaging of the skin and the alterations associated with it can manifest in different ways, including: loss of firmness and elasticity due to tissue loss in the epidermis and /or the dermis; loss of radiance due to reduced microcirculation and a slowdown in cell renewal in the epidermis; the appearance of pigment spots; and/or skin dryness resulting from a reduction in the barrier function of the stratum corneum and a slowdown in epidermal renewal.
  • an alcoholic extract of white lily flowers, Lilium candidum L. obtained by a particular process, presents, through stimulation or inhibition of physiological mechanisms, interesting activities with respect to against skin aging, in particular via protective properties against oxidative stress giving it antioxidant potential.
  • the alcoholic extract of white lily flowers, Lilium candidum L. presents interesting cosmetic properties: it allows activation of the biological “response to oxidative stress mediated by NRF2” pathway.
  • aging of the dermis is characterized in particular by the progressive differentiation of papillary fibroblasts into reticular fibroblasts leading to stiffening of the dermis.
  • the alcoholic extract of white lily flowers, Lilium candidum L allows an increase in the expression of the papillary markers CCRL1, NTN and PDPN as well as a reduction in the expression of the reticular markers CDH2, CNN and MGP in reticular fibroblasts.
  • the extract according to the invention also has an anti-aging effect on the skin, because it makes it possible to improve the morphology of the epidermis, in particular by promoting its thickening in models of aged skin reconstructed with reticular fibroblasts.
  • the invention therefore relates, according to a first aspect, to an alcoholic extract of white lily flowers, Lilium candidum L., comprising at least lilidine glycoside and hopantenic acid.
  • the invention also relates, according to a second aspect, to a process for extracting white lily flowers, Lilium candidum L., comprising at least the following steps: a) grinding white lily flowers, Lilium candidum L., b) at least one, preferably at least two extractions of said crushed flowers in the presence of an alcoholic solvent, each extraction being followed by a filtration step; c) mixing the liquid filtrates resulting from the extractions of step b) and resting the mixture obtained for at least 6 hours, preferably at least 1Oh; d) filtration of the mixture obtained in c); e) elimination of the mono-alcoholic solvent from the mixture obtained in d), and final dilution in another alcoholic solvent.
  • the invention also relates to an alcoholic extract of white lily flowers, Lilium candidum L. capable of being obtained by such a process.
  • the invention also relates to a cosmetic composition comprising, in a cosmetically acceptable vehicle, an alcoholic extract of white lily flowers, Lilium candidum L. according to the invention.
  • cosmetically acceptable vehicle is meant a medium compatible with the skin, mucous membranes and integuments.
  • the cosmetic composition according to the invention is suitable for topical application.
  • the white brackets illustrate the differences in thickness of living epidermis observed.
  • the raw material used consists of flowers, fresh or dried, of white lily, Lilium candidum L.
  • Lilium candidum L. is a herbaceous plant of the liliaceae family called the white lily, Madonna lily, Lily or white flower lily (Madonna lily, white lily in English).
  • the Madonna Lily is a bulbous perennial plant with fleshy scales of the Liliaceae family, which can reach 1.8 m high.
  • the scaly bulb produces basal leaves, forming a rosette.
  • the spectacular flowering offers 5 to 10 trumpet-shaped flowers, immaculate white, 15 cm long, composed of 6 large tepals, a long pistil and 6 long stamens. Flowering takes place in June.
  • the dry extract of Lilium candidum L. object of the present invention is composed of several families of primary and secondary metabolites of interest.
  • the alcoholic extract of white lily flowers, Lilium candidum L., which is the subject of the present invention, comprises in particular at least lilidine glycoside and hopantenic acid.
  • the alcoholic extract of Lilium candidum L. of the invention comprises:
  • the di-0 and tri-O-glycosylated kaempferol derivatives are compounds with the following structure I (which corresponds to Kaempferol Tri-O-glycopyranoside) or II (which corresponds to Kaempferol di-O-glycopyranoside):
  • Lilidine glycoside is a compound corresponding to the following formula III:
  • Hopantenic acid has the following structure IV:
  • the saccharides present in the Lily extract according to the invention preferably comprise glucose, fructose and/or sucrose, and in particular 20 to 25% by weight of fructose, 17 to 21% by weight of glucose and 5 to 11 % by weight of sucrose.
  • Lily extract comprising in particular lilidine glycoside, hopantenic acid and preferably di-0 and tri-O-glycosylated kaempferol derivatives, which makes it its specificity.
  • the alcoholic extract of Lilium candi dum of the invention can in particular be obtained by means of a process for extracting white lily flowers, Lilium candidum L. L., comprising the following steps: a) grinding the white lily flowers, Lilium candidum L. L., b) at least one, preferably at least two extractions of said crushed flowers in the presence of an alcoholic solvent, each extraction being followed by a filtration step; c) mixing the liquid filtrates resulting from the extractions of step b) and resting the mixture obtained for at least 6 hours, preferably at least 1Oh; d) filtration of the mixture obtained in c); e) elimination of the mono-alcoholic solvent from the mixture obtained in d), and final dilution in another alcoholic solvent.
  • the white lily flowers used in step a) are fresh flowers or dried flowers.
  • step b) the crushed white lily flowers are subjected to at least one, preferably at least two, extractions with one or more alcoholic solvents, for example chosen from:
  • - C1-C4 monoalcohols such as for example methanol, ethanol or isopropanol
  • - diols such as for example propylene glycol, 1,3-propanediol or dipropylene glycol.
  • the alcoholic solvent is a monoalcohol comprising 2 to 4 carbon atoms, more preferably ethanol.
  • the alcoholic solvent is used in a mixture of at least 90% with water, preferably at least 95% with water.
  • the alcoholic solvent is used in a mixture of between 90% and 99% with water, preferably between 95% and 99% with water.
  • the ethanol is used as a mixture of at least 90% with water, preferably at least 95% with water.
  • the ethanol is used as a mixture of between 90% and 99% with water, preferably between 95% and 99% with water.
  • ethanol is used as a 96% mixture with water.
  • the extraction is generally carried out by immersing and gently shaking the white lily flowers in one or more of the solvents mentioned above for a period of between 1 and 6 hours, at a temperature of between 40°C and 60°C, preferably between 45 and 55°C.
  • Extraction step b) is followed by filtration, for example on a 50 pm sieve, to eliminate plant residues.
  • step b) implements at least two extractions.
  • each extraction is followed by a filtration step.
  • the liquid filtrates are recovered and mixed.
  • the filtrate mixture is then left to stand for at least 6 hours, preferably at least 10 hours.
  • step d) The filtrate or mixture of filtrates obtained at the end of step c) is then filtered again in order to eliminate insoluble substances: this is step d).
  • the filtration of the extract obtained in c) is carried out on a sieve or a 4 ⁇ m filtration membrane. A liquid filtrate is thus obtained. Finally, the solvent present in the liquid filtrate is removed, and the remaining filtrate is diluted in another alcoholic solvent (step e)).
  • the order of the steps of removing the solvent and diluting the filtrate in another solvent is irrelevant.
  • the solvent present in the liquid filtrate can be removed, then the remaining filtrate is diluted in another alcoholic solvent.
  • the liquid filtrate is first diluted in another alcoholic solvent, and the solvents are then removed.
  • the dilution of the filtrate and the elimination of solvents can be simultaneous.
  • the alcohol solvent used in step e) is called “other alcohol solvent” because it is different from the alcohol solvent used in step a).
  • the alcoholic solvent is typically chosen from the same group as that of step a), i.e. from C1-C4 monoalcohols and diols.
  • the final dilution is carried out in a diol, preferably 1,3-propanediol.
  • the elimination of the solvent from step e) is done by evaporation, in particular by evaporation under vacuum.
  • a step of decolorization of the filtrate obtained in d) is added.
  • Decolorization can be done by adsorption of the pigments present in the filtrate on activated carbon.
  • This decolorization step can be followed by a filtration step of the decolorized filtrate obtained, in particular up to Ipm.
  • the alcoholic extract of white lily flowers, Lilium candidum L can be obtained by a process comprising the following steps: a) grinding the white lily flowers, Lilium candidum L., b ) at least one, preferably at least two extractions of said crushed flowers in the presence of an alcoholic solvent, each extraction being followed by a filtration step; c) mixing the at least two liquid filtrates resulting from the two extractions of step b) and resting the mixture obtained for at least 6 hours, preferably at least 1Oh; d) filtration of the mixture obtained in c) to obtain a filtrate; decolorization of the filtrate obtained in d) by adsorption on activated carbon; Then - filtration of the decolorized filtrate on a 1 ⁇ m membrane; and e) removal of ethanol from the filtrate obtained by evaporation, then final dilution in 1,3-propanediol.
  • the extract used according to the invention is light in color.
  • said extract is in a sufficiently concentrated form to be able to be used without causing the formulation problems usually encountered at the concentrations necessary to obtain activity in cosmetic or dermatological compositions in emulsion form, and without presenting a dark color, unlike to plant extracts obtained by usual processes, when they are in concentrated form.
  • the extract of white Lily flowers comprises 15 to 25% by weight of dry Lily extract and 75 to 85% by weight of 1,3-propanediol , and preferably, approximately 20% by weight of dry extract of Lys and 80% by weight of 1,3-propanediol.
  • the extract according to the invention can be used directly for the preparation of a cosmetic composition.
  • the invention relates to the cosmetic use of an alcoholic extract of white lily flowers, Lilium candidum L., according to the invention, as an antioxidant and/or anti-aging agent.
  • the invention relates to the cosmetic use of an alcoholic extract of white lily flowers, Lilium candidum L., according to the invention, for the prevention and/or attenuation of alterations of the skin due to aging. And in particular, as an agent for activating the response to oxidative stress mediated by NRF2 and/or an agent promoting thickening of the epidermis.
  • the alcoholic extract of white lily flowers, Lilium candidum L. possessed several activities of interest with regard to preventive or restorative physiological mechanisms linked to alterations. of the skin, particularly due to aging. It was notably found, advantageously, that the alcoholic extract of white lily flowers, Lilium candidum L, according to the invention allowed an increase in the expression of the papillary markers CCRL1, NTN and PDPN as well as a reduction in the expression of the reticular markers CDH2, CNN and MGP in reticular fibroblasts.
  • the extract according to the present invention also makes it possible to improve the morphology of the epidermis, in particular by promoting its thickening in models of aged skin reconstructed with reticular fibroblasts.
  • the invention also relates, according to yet another aspect, to a cosmetic composition
  • a cosmetic composition comprising, in a cosmetically acceptable vehicle, an alcoholic extract of white lily flowers, Lilium candidum L., according to the invention.
  • said extract is present in the cosmetic or dermatological composition in an amount of 0.001 to 10% by weight, relative to the total weight of the composition, in particular in an amount of 0.01 to 10% by weight, preferably 0 .1 to 10% by weight.
  • Said cosmetic composition may in particular be adapted for topical application.
  • said cosmetic composition can be in the form of a powder, an emulsion, a microemulsion, a nanoemulsion, a suspension, a solution of a lotion, a cream, an aqueous or hydroalcoholic gel, a foam, a serum, a solution or dispersion for aerosol, or a dispersion of lipid vesicles.
  • an emulsion in the case of an emulsion, it can be a water-in-oil or oil-in-water emulsion.
  • the cosmetic composition according to the invention may also comprise a solvent chosen according to the different ingredients and the form of administration.
  • water preferably demineralized water or floral waters
  • alcohol such as ethanol
  • Said cosmetic composition may also comprise, in addition to the extract according to the invention, at least one usual additive in the field, such as for example at least one compound chosen from an emollient or humectant agent, a gelling and/or thickening agent. , a surfactant, an oil, an active agent, a coloring, a preservative, a antioxidant agent, an active agent, an organic or inorganic powder, a sunscreen and a perfume.
  • at least one usual additive in the field such as for example at least one compound chosen from an emollient or humectant agent, a gelling and/or thickening agent.
  • a surfactant an oil, an active agent, a coloring, a preservative, a antioxidant agent, an active agent, an organic or inorganic powder, a sunscreen and a perfume.
  • humectant(s) such as polyols (glycerin, diglycerin, propylene glycol, propanediol, caprylyl glycol, pentylene glycol, hexanediol), sugars, glycosaminoglycans such as hyaluronic acid and its salts and esters; and polyquatemiums such as PMB lipid
  • Said humectant will be present in the composition at a content of the order of 0.1 to 30%, preferably 0.005 to 10% by total weight of the composition.
  • One or more emollient agent(s) which can be chosen for example from esters such as jojoba esters, esters of fatty acids and fatty alcohol (octyldodecyl myristate, triethylhexanoin, Dicaprylyl carbonate , Isostearyl isostearate, caprylic/capric triglyceride), butters such as shea butters (butyrospemum parkii butter extract, shea butter ethyl esters, marketed under the names LIPEX SHEASOFT, LIPEX SHEA-U, LIPEX SHEA, LIPEX SHEALIGHT, LIPEX SHEA TRIS) or moringa (moringa oil/hydrogenated moringa oil esters), waxes (acacia decurrens flower wax & helianthus annuus cera seed seed wax, Cl 0-18 triglycerides), vegetable oils, phytosqualane, alkanes
  • Said emollient agent will be present in the composition at a content of the order of 0.1 to 30%, preferably 0.5 to 10% by total weight of the composition.
  • One or more gelling agent(s) and/or thickener(s) of the aqueous phase chosen for example from cellulose derivatives, gums of plant origin (guar, carob, alginates, carrageenans, pectins), d microbial origin (xanthan), clays (laponite), homo- and copolymers, crosslinked or not, hydrophilic or amphiphilic, of acryloylmethylpropane sulfonic acid (AMPS) and/or acrylamide and/or acrylic acid and/or salts or esters of acrylic acid (marketed under the names ARISTOFLEX AVC, Aristoflex AVS, Aristoflex HMB, SIMULGEL NS, Simulgel EG, Simulgel 600, Simulgel 800, Pemulen, carbopol, Sepiplus 400, Seppimax zen, Sepiplus S, COSMEDIA SP)
  • cellulose derivatives gums of plant origin (guar, carob, alginates, carrageenans, pectins
  • Said gelling and/or thickening agent will be present in the composition at a content of the order of 0.1 to 10% by total weight of the composition.
  • anionic surfactants such as isethionates, taurates, sarcosinates, glycinates, glutamates, phosphates (C20-22 alkyl phosphate marketed under the name SENSANOV WR)
  • amphoteric surfactants such as betaine derivatives, amphoacetates
  • non-ionic surfactants such as polyglycerol derivatives, sugar derivatives (glucoside or xyloside derivatives marketed under the name MONTANOV 68, MONTANOV 202, Montanov 82, MONTANOV L, EASYNOV), lecithins.
  • Said surfactant will be present in a content of the order of 0.1 to 15%, preferably 0.5 to 10% by weight, relative to the total weight of the composition.
  • One or more active agent(s) of natural, biotechnological or synthetic origin having biological activity and having effectiveness on the skin via biological sites for example chosen from vitamins such as vitamin C and its derivatives (ascorbyl glucoside, 3-o-ethyl ascorbic acid, ascorbyl tetraisopalmitate), vitamin A and its derivatives, vitamin E and its derivatives, vitamin B3 or Niacinamide, panthenol, trace elements, Allantoin , adenosine, peptides (Palmitoyl tetrapeptide-7, Palmitoyl Tripeptide-1, Palmitoyl Pentapeptide-4, Acetyl Dipeptide-1 Cetyl Ester, Acetyl Tetrapeptide-5 marketed under the name NP RIGIN, MATRIXYL 3000, IDEALIFT, EYESERYL), plant extracts (glycyrrhiza glabra extract, centella asiatica leaf extract, secale cereale seed extract,
  • Said active agent will be present in the composition at a content of the order of 0.1 to 10% by total weight of the composition.
  • additives usually used in cosmetics may also be present in the composition according to the invention, in particular preservatives, antioxidant agents or perfumes well known in the technical field.
  • Example 1 Preparation of an alcoholic extract of white lily flowers, Lilium candidum according to the invention
  • An alcoholic extract of white lily flowers, Lilium candidum L., according to the invention is prepared by a process comprising the following steps: a) grinding 200g white lily flowers, Lilium candidum L., into powder b) Extraction of the powder in 2000g of 96° ethanol with stirring at 50°C for 2 hours;
  • Example 2 Test of the properties of the Lily extract according to the invention against oxidative stress.
  • FC fold change, expression level vs. untreated condition
  • the extract is capable of modulating on average the expression of 158 genes (including 59 inhibited and 99 stimulated) in normal human keratinocytes after 24 hours of treatment.
  • IP A software was used to evaluate changes in biological activity after treatment with the extract.
  • a map representing the modulation of the expression of different biological pathways was established (data not provided).
  • the transcriptomic map obtained after 24 hours of treatment reveals the modulation of numerous biological functions with 0.25% extract.
  • the Madonna Lily is notably capable of modulating 64 canonical signaling pathways.
  • NRF2 nuclear factor erythroid 2-related factor 2
  • NRF2 is a transcription factor which, once activated, increases the expression of antioxidant enzymes such as GCLM, GPX, GST, NQO1, SOD and TXNR.
  • NRF2 also activates the transcription of non-enzymatic antioxidant proteins such as ferritin, composed in particular of the FTL and FTH1 subunits.
  • the stimulation of this biological pathway of global cellular detoxification in normal keratinocytes after 24 hours of treatment with the 0.25% extract gives it antioxidant and anti-aging properties, as oxidative stress contributes to skin aging.
  • NRF2 Nuclear factor 2 related to factor erythroid 2
  • FC expression level vs untreated condition
  • Example 3 Anti-aging properties of the Lily extract according to the invention in cellular and tissue models of skin aging.
  • the dermis can be divided into two subpopulations of fibroblasts: papillary fibroblasts, located under the epidermis at the level of the papillae and which present a younger phenotype, and reticular fibroblasts, more
  • This aging can be modeled in the laboratory, at the cellular level, using reticular fibroblasts and, at the tissue level, by reconstructing equivalent skin with a dermis synthesized by reticular fibroblasts. These models can thus be used to identify ingredients with anti-aging properties capable of reversing dermal aging.
  • the complementary DNAs were synthesized (iScript kit, Biorad) then the qPCR reactions were carried out with the SYBR Green method (Biorad) following this program: 5 min at 95°C then 35 cycles with 20 seconds at 95°C, 20 seconds at 60°C and 20 seconds at 72°C followed by the generation of melting curves.
  • Expression analyzes were carried out with iQ5 software (Biorad) using the AACt method with stably expressed reference genes. The expression of biomarkers specific to papillary (CCRL1, NTN and PDPN) and reticular (CDH2, CNN and MGP) fibroblasts was thus evaluated in the samples.
  • the extract is able to increase the expression of papillary markers CCRL1, NTN and PDPN as well as decrease the expression of reticular markers CDH2, CNN and MGP in reticular fibroblasts after 96 hours of treatment. Lys extract therefore has the capacity to reverse the aged phenotype of reticular fibroblasts into a younger phenotype, close to that of papillary fibroblasts.
  • Tissue model protocol Normal human papillary or reticular dermal fibroblasts from three donors were seeded and cultured in DMEM medium supplemented with 5% serum (HyClone) for 5 days at 37°C and 5% CO2. The cells were then incubated or not (control condition) with 0.25% extract or with 0.25% propandiol solvent (diluent only condition) for 4 days. Equivalent dermis were generated with the treated or control cells then they were incubated again or not with 0.25% Lys extract or propandiol in DMEM medium supplemented with 5% serum and 1% penicillin-streptomycin (Invitrogen) at 37°C and 5% CO2, for 7 days.
  • Hematoxylin saffron eosin (HSE) staining was carried out in order to observe their overall morphology and in particular the thickness of the epidermis which becomes thinner in reticular aged skin models (“young” papillary skin) 6 .
  • Immunostaining for Ki67 was also carried out to count positive cells in skin reconstructed with papillary fibroblasts.
  • Antigenic unmasking was carried out in citrate buffer at pH6, before incubation in a blocking solution preventing nonspecific binding of the antibodies.
  • the sections are then incubated overnight at 4°C with a primary antibody specifically targeting Ki67 (MIB-1, Dako) then with the avidin-biotin-peroxidase system following the supplier's recommendations (GE Healthcare).
  • Ki67 MIB-1, Dako
  • the marking was visualized by adding AEC (3-amino-9-ethylcarbazole) and the sections were counterstained using hematoxylin.
  • the Lily extract according to the invention is capable of improving the morphology of the epidermis, in particular by promoting its thickening (right), in models of aged skin reconstructed with reticular fibroblasts compared to untreated conditions (center). The skin treated with the extract thus regains a younger morphology, close to that obtained with skin reconstructed with untreated papillary fibroblasts (left).
  • the extract is also capable of increasing the number of cells expressing the proliferation marker Ki67 in the basal layer of skin reconstructed with papillary fibroblasts. It therefore promotes cell renewal.
  • Lys extract is capable of slowing down dermal aging by modifying a reticular phenotype into a younger papillary phenotype in cellular and tissue models. It therefore has strong anti-aging properties.
  • Example 4 cosmetic compositions
  • compositions can be prepared in a conventional manner for those skilled in the art.
  • quantities indicated below are expressed as percentages by weight.
  • Ingredients in capital letters are identified in accordance with the INCI name.
  • compositions can be applied every day, morning and/or evening, to the skin.

Abstract

The invention relates to an extract of white lily flowers Lilium candidum L, a method for obtaining same, and a cosmetic composition containing same, as well as different cosmetic uses.

Description

Extrait alcoolique de fleurs Lys blanc, Lilium candidumL., son procédé d’obtention, et composition cosmétique le contenant Alcoholic extract of white lily flowers, Lilium candidumL., process for obtaining it, and cosmetic composition containing it
L’invention concerne un extrait de fleurs Lys blanc, Lilium candidum L., son procédé d’obtention, une composition cosmétique le contenant, ainsi que différentes utilisations cosmétiques. The invention relates to an extract of white lily flowers, Lilium candidum L., its process for obtaining it, a cosmetic composition containing it, as well as different cosmetic uses.
La peau est principalement constituée de trois couches, à savoir, en partant de la plus superficielle, l’épiderme, le derme et l’hypoderme. The skin is mainly made up of three layers, namely, starting from the most superficial, the epidermis, the dermis and the hypodermis.
L’épiderme contribue largement à assurer la protection de la peau et à en maintenir son bon fonctionnement. The epidermis largely contributes to protecting the skin and maintaining its proper functioning.
Le vieillissement et le photo-vieillissement de la peau et les altérations qui y sont associées peuvent se manifester de différentes manières, parmi lesquelles on peut citer : la perte de fermeté et d’élasticité dues à une perte tissulaire au niveau de l’épiderme et/ou du derme ; la perte d’éclat due à la réduction de la microcirculation et à un ralentissement du renouvellement cellulaire au niveau de l’épiderme ; l’apparition de taches pigmentaires; et/ou la sécheresse cutanée résultant d’une diminution de la fonction barrière de la couche cornée et d’un ralentissement du renouvellement épidermique. Aging and photoaging of the skin and the alterations associated with it can manifest in different ways, including: loss of firmness and elasticity due to tissue loss in the epidermis and /or the dermis; loss of radiance due to reduced microcirculation and a slowdown in cell renewal in the epidermis; the appearance of pigment spots; and/or skin dryness resulting from a reduction in the barrier function of the stratum corneum and a slowdown in epidermal renewal.
Il existe, de ce fait, un besoin de fournir un agent actif polyfonctionnel susceptible d’agir sur un ensemble de causes d’altérations de la peau dues au vieillissement et/ou à une modification des mécanismes physiologiques liés au vieillissement. There is, therefore, a need to provide a polyfunctional active agent capable of acting on a set of causes of skin alterations due to aging and/or a modification of the physiological mechanisms linked to aging.
Or, la Demanderesse a maintenant trouvé qu’un extrait alcoolique de fleurs Lys blanc, Lilium candidum L., obtenu par un procédé particulier, présente, par le biais de stimulation ou d’inhibition de mécanismes physiologiques, des activités intéressantes vis- à-vis du vieillissement cutané, en particulier via des propriétés protectrices contre le stress oxydatif lui conférant un potentiel antioxydant. En effet, comme démontré en exemples, l’extrait alcoolique de fleurs Lys blanc, Lilium candidum L., selon l’invention présente des propriétés cosmétiques intéressantes : il permet une activation de la voie biologique de « réponse au stress oxydatif médiée par NRF2 ». En outre, le vieillissement du derme se caractérise notamment par la différenciation progressive des fibroblastes papillaires en fibroblastes réticulaires conduisant à une rigidification du derme. Or l’extrait alcoolique de fleurs Lys blanc, Lilium candidum L, selon l’invention permet une augmentation de l’expression des marqueurs papillaires CCRL1, NTN et PDPN ainsi qu’une diminution de l’expression des marqueurs réticulaires CDH2, CNN et MGP dans des fibroblastes réticulaires. However, the Applicant has now found that an alcoholic extract of white lily flowers, Lilium candidum L., obtained by a particular process, presents, through stimulation or inhibition of physiological mechanisms, interesting activities with respect to against skin aging, in particular via protective properties against oxidative stress giving it antioxidant potential. Indeed, as demonstrated in examples, the alcoholic extract of white lily flowers, Lilium candidum L., according to the invention presents interesting cosmetic properties: it allows activation of the biological “response to oxidative stress mediated by NRF2” pathway. In addition, aging of the dermis is characterized in particular by the progressive differentiation of papillary fibroblasts into reticular fibroblasts leading to stiffening of the dermis. However, the alcoholic extract of white lily flowers, Lilium candidum L, according to the invention allows an increase in the expression of the papillary markers CCRL1, NTN and PDPN as well as a reduction in the expression of the reticular markers CDH2, CNN and MGP in reticular fibroblasts.
L’extrait selon l’invention présente en outre un effet anti-vieillissement de la peau, car il permet d’améliorer la morphologie de l’épiderme, notamment en favorisant son épaississement dans des modèles de peaux âgées reconstruites avec des fibroblastes réticulaires. The extract according to the invention also has an anti-aging effect on the skin, because it makes it possible to improve the morphology of the epidermis, in particular by promoting its thickening in models of aged skin reconstructed with reticular fibroblasts.
L’invention concerne donc, selon un premier aspect, un extrait alcoolique de fleurs Lys blanc, Lilium candidum L., comprenant au moins de la lilidine glycoside et de l’acide hopanténique. The invention therefore relates, according to a first aspect, to an alcoholic extract of white lily flowers, Lilium candidum L., comprising at least lilidine glycoside and hopantenic acid.
L’invention a également pour objet, selon un second aspect, un procédé d’extraction de fleurs Lys blanc, Lilium candidum L., comprenant au moins les étapes suivantes : a) le broyage des fleurs de Lys blanc, Lilium candidum L., b) au moins une, de préférence au moins deux extractions desdites fleurs broyées en présence d’un solvant alcoolique, chaque extraction étant suivie d’une étape de filtration ; c) le mélange des filtrats liquides issus des extractions de l’étape b) et repos du mélange obtenu pendant au moins 6h, de préférence au moins lOh ; d) filtration du mélange obtenu en c) ; e) élimination du solvant mono-alcoolique du mélange obtenu en d), et dilution finale dans un autre solvant alcoolique. The invention also relates, according to a second aspect, to a process for extracting white lily flowers, Lilium candidum L., comprising at least the following steps: a) grinding white lily flowers, Lilium candidum L., b) at least one, preferably at least two extractions of said crushed flowers in the presence of an alcoholic solvent, each extraction being followed by a filtration step; c) mixing the liquid filtrates resulting from the extractions of step b) and resting the mixture obtained for at least 6 hours, preferably at least 1Oh; d) filtration of the mixture obtained in c); e) elimination of the mono-alcoholic solvent from the mixture obtained in d), and final dilution in another alcoholic solvent.
L’invention se rapporte également à un extrait alcoolique de fleurs Lys blanc, Lilium candidum L. susceptible d’être obtenu par un tel procédé. L’invention se rapporte en outre aussi à une composition cosmétique comprenant, dans un véhicule cosmétiquement acceptable, un extrait alcoolique de fleurs Lys blanc, Lilium candidum L. selon l’invention. Par véhicule cosmétiquement acceptable, on entend un milieu compatible avec la peau, les muqueuses et les phanères. De préférence, la composition cosmétique selon l’invention est adaptée à une application par voie topique. The invention also relates to an alcoholic extract of white lily flowers, Lilium candidum L. capable of being obtained by such a process. The invention also relates to a cosmetic composition comprising, in a cosmetically acceptable vehicle, an alcoholic extract of white lily flowers, Lilium candidum L. according to the invention. By cosmetically acceptable vehicle is meant a medium compatible with the skin, mucous membranes and integuments. Preferably, the cosmetic composition according to the invention is suitable for topical application.
Figures : Figures:
La Figure 1 illustre l’expression relative ( s condition non traitée) de marqueurs papillaires (CCRL1, NTN, PDPN) et réticulaires (CDH2, CNN, MGP) dans des fibroblastes réticulaires (ret) traités par l’extrait de Lys à 0,25% pendant 96h (n=3 donneurs DI à D3). Figure 1 illustrates the relative expression (s untreated condition) of papillary (CCRL1, NTN, PDPN) and reticular (CDH2, CNN, MGP) markers in reticular fibroblasts (ret) treated with Lys extract at 0, 25% for 96 hours (n=3 donors DI to D3).
La Figure 2 illustre la morphologie globale de peaux reconstruites avec des fibroblastes papillaires (à gauche) ou des fibroblastes réticulaires (au centre et à droite), non traitées (contrôle, à gauche et au centre) ou traitées l’extrait de Lys à 0,25% (à droite) sur n=3 donneurs (DI à D3). Les crochets blancs illustrent les différences d’épaisseur d’épiderme vivant observées. Figure 2 illustrates the overall morphology of skin reconstructed with papillary fibroblasts (left) or reticular fibroblasts (center and right), untreated (control, left and center) or treated with Lys extract at 0 .25% (right) on n=3 donors (DI to D3). The white brackets illustrate the differences in thickness of living epidermis observed.
La Figure 3 indique le pourcentage de cellules exprimant le marqueur de prolifération Ki67 dans des peaux reconstruites comportant des fibroblastes papillaires non traitées (contrôle), traitées avec le solvent contrôle (propanediol) ou traitées avec l’extrait de Lys à 0,25% (n=3 donneurs DI à D3). Figure 3 indicates the percentage of cells expressing the proliferation marker Ki67 in reconstructed skin containing untreated papillary fibroblasts (control), treated with the control solvent (propanediol) or treated with 0.25% Lys extract ( n=3 donors DI to D3).
La matière première mise en œuvre est constituée des fleurs, fraiches ou séchées, de Lys blanc, Lilium candidum L. The raw material used consists of flowers, fresh or dried, of white lily, Lilium candidum L.
Lilium candidum L. est une plante herbacée de la famille des liliacées appelé le lis blanc, lys de la Madone, Lys ou Lys à fleurs blanches (Madonna lily, white lily en anglais). Lilium candidum L. is a herbaceous plant of the liliaceae family called the white lily, Madonna lily, Lily or white flower lily (Madonna lily, white lily in English).
Le Lys de la Madone est une plante vivace bulbeuse à écailles charnues de la famille des Liliacées, pouvant atteindre 1,8 m de haut. The Madonna Lily is a bulbous perennial plant with fleshy scales of the Liliaceae family, which can reach 1.8 m high.
Le bulbe écailleux produit des feuilles basales, formant une rosette. The scaly bulb produces basal leaves, forming a rosette.
Les feuilles, portées par des tiges robustes, sont brillantes, pointues, alternées et de taille décroissante. La floraison spectaculaire offre 5 à 10 fleurs en forme de trompette, d'un blanc immaculé, longues de 15 cm, composées de 6 gros tépales, d'un long pistil et de 6 longues étamines. La floraison a lieu en juin. The leaves, borne on sturdy stems, are shiny, pointed, alternate and decreasing in size. The spectacular flowering offers 5 to 10 trumpet-shaped flowers, immaculate white, 15 cm long, composed of 6 large tepals, a long pistil and 6 long stamens. Flowering takes place in June.
Le Lys de la Madone est cultivé en France The Madonna Lily is grown in France
L’extrait sec de Lilium candidum L. objet de la présente invention est composé de plusieurs familles de métabolites primaires et secondaires d’intérêt. The dry extract of Lilium candidum L. object of the present invention is composed of several families of primary and secondary metabolites of interest.
L’extrait alcoolique de fleurs de Lys blanc, Lilium candidum L. objet de la présente invention comprend notamment au moins de la lilidine glycoside et de l’acide hopanténique The alcoholic extract of white lily flowers, Lilium candidum L., which is the subject of the present invention, comprises in particular at least lilidine glycoside and hopantenic acid.
En particulier, l’extrait alcoolique de Lilium candidum L. de l’invention comprend : In particular, the alcoholic extract of Lilium candidum L. of the invention comprises:
- 40 à 70% en poids de saccharides, de préférence 50 à 60% en poids,- 40 to 70% by weight of saccharides, preferably 50 to 60% by weight,
- 1 à 5% en poids de composés dérivés du kaempferol di-0 et tri-O- glycosylé, de préférence 2,5 à 3,2% en poids, - 1 to 5% by weight of compounds derived from di-0 and tri-O-glycosylated kaempferol, preferably 2.5 to 3.2% by weight,
- 8 à 15% en poids de lilidine glycoside, de préférence 10 à 13% en poids, et- 8 to 15% by weight of lilidine glycoside, preferably 10 to 13% by weight, and
- 1 à 5% en poids d’acide hopanténique, de préférence 2 à 3% en poids, les pourcentages étant exprimés en poids, par rapport au poids total de l’extrait. Les dérivés du kaempferol di-0 et tri-O-glycosylé sont des composés de structure I (qui correspond au Kaempferol Tri-O-glycopyranoside) ou II (qui correspond au Kaempferol di-O-glycopyranoside) suivantes :
Figure imgf000005_0001
- 1 to 5% by weight of hopantenic acid, preferably 2 to 3% by weight, the percentages being expressed by weight, relative to the total weight of the extract. The di-0 and tri-O-glycosylated kaempferol derivatives are compounds with the following structure I (which corresponds to Kaempferol Tri-O-glycopyranoside) or II (which corresponds to Kaempferol di-O-glycopyranoside):
Figure imgf000005_0001
La lilidine glycoside est un composé répondant à la formule III suivante :
Figure imgf000005_0002
Lilidine glycoside is a compound corresponding to the following formula III:
Figure imgf000005_0002
L’acide hopanténique répond quant à lui à la structure IV suivante :
Figure imgf000006_0001
Hopantenic acid has the following structure IV:
Figure imgf000006_0001
Les saccharides présents dans l’extrait de Lys selon l’invention comprennent de préférence du glucose, du fructose et/ou du sucrose, et notamment 20 à 25% en poids de fructose, 17 à 21% en poids de glucose et 5 à 11% en poids de sucrose. The saccharides present in the Lily extract according to the invention preferably comprise glucose, fructose and/or sucrose, and in particular 20 to 25% by weight of fructose, 17 to 21% by weight of glucose and 5 to 11 % by weight of sucrose.
Il est du mérite de la demanderesse d’avoir réussi à préparer un extrait de Lys comprenant notamment de la lilidine glycoside, de l’acide hopanténique et préférentiellement des dérivés du kaempferol di-0 et tri-O-glycosylé, ce qui en fait sa spécificité. It is to the applicant's credit to have succeeded in preparing a Lily extract comprising in particular lilidine glycoside, hopantenic acid and preferably di-0 and tri-O-glycosylated kaempferol derivatives, which makes it its specificity.
L’extrait alcoolique de Lilium candi dum de l’invention peut notamment être obtenu au moyen d’un procédé d’extraction des fleurs de Lys blanc, Lilium candidum L. L., comprenant les étapes suivantes : a) le broyage des fleurs de Lys blanc, Lilium candidum L. L., b) au moins une, de préférence au moins deux extractions desdites fleurs broyées en présence d’un solvant alcoolique, chaque extraction étant suivie d’une étape de filtration ; c) le mélange des filtrats liquides issus des extractions de l’étape b) et repos du mélange obtenu pendant au moins 6h, de préférence au moins lOh ; d) filtration du mélange obtenu en c) ; e) élimination du solvant mono-alcoolique du mélange obtenu en d), et dilution finale dans un autre solvant alcoolique. The alcoholic extract of Lilium candi dum of the invention can in particular be obtained by means of a process for extracting white lily flowers, Lilium candidum L. L., comprising the following steps: a) grinding the white lily flowers, Lilium candidum L. L., b) at least one, preferably at least two extractions of said crushed flowers in the presence of an alcoholic solvent, each extraction being followed by a filtration step; c) mixing the liquid filtrates resulting from the extractions of step b) and resting the mixture obtained for at least 6 hours, preferably at least 1Oh; d) filtration of the mixture obtained in c); e) elimination of the mono-alcoholic solvent from the mixture obtained in d), and final dilution in another alcoholic solvent.
De préférence, les fleurs de Lys blanc mises en œuvre à l’étape a) sont des fleurs fraîches ou des fleurs séchées. Preferably, the white lily flowers used in step a) are fresh flowers or dried flowers.
Elles sont notamment broyées ou réduites en morceaux, par exemple à une finesse inférieure à 2 cm, par tout moyen connu de l’homme du métier. They are in particular crushed or reduced into pieces, for example to a fineness of less than 2 cm, by any means known to those skilled in the art.
Dans l’étape b), les fleurs de Lys blanc broyées sont soumises à au moins une, de préférence au moins deux extractions par un ou plusieurs solvants alcooliques, par exemple choisis parmi : In step b), the crushed white lily flowers are subjected to at least one, preferably at least two, extractions with one or more alcoholic solvents, for example chosen from:
- les monoalcools en C1-C4, tels que par exemple le méthanol, l’éthanol ou l’isopropanol ; et - les diols, tels que par exemple le propylène glycol, le 1,3 -propanediol ou le dipropylène glycol. - C1-C4 monoalcohols, such as for example methanol, ethanol or isopropanol; And - diols, such as for example propylene glycol, 1,3-propanediol or dipropylene glycol.
De préférence, le solvant alcoolique est un monoalcool comprenant de 2 à 4 atomes de carbone, plus préférentiellement l’éthanol. Preferably, the alcoholic solvent is a monoalcohol comprising 2 to 4 carbon atoms, more preferably ethanol.
De préférence, le solvant alcoolique est mis en œuvre en mélange à au moins 90% avec de l’eau, de préférence au moins 95% avec de l’eau. De préférence, le solvant alcoolique est mis en œuvre en mélange entre 90% et 99% avec de l’eau, de préférence entre 95% et 99% avec de l’eau. Preferably, the alcoholic solvent is used in a mixture of at least 90% with water, preferably at least 95% with water. Preferably, the alcoholic solvent is used in a mixture of between 90% and 99% with water, preferably between 95% and 99% with water.
De préférence, l’éthanol est mis en œuvre en mélange à au moins 90% avec de l’eau, de préférence au moins 95% avec de l’eau. De préférence, l’éthanol est mis en œuvre en mélange entre 90% et 99% avec de l’eau, de préférence entre 95% et 99% avec de l’eau. Preferably, the ethanol is used as a mixture of at least 90% with water, preferably at least 95% with water. Preferably, the ethanol is used as a mixture of between 90% and 99% with water, preferably between 95% and 99% with water.
En particulier, l’éthanol est mis en œuvre en mélange à 96% avec de l’eau. In particular, ethanol is used as a 96% mixture with water.
L’extraction est généralement réalisée en immergeant et en agitant doucement les fleurs de Lys blanc dans un ou plusieurs des solvants cités ci-dessus pendant une durée comprise entre 1 et 6 heures, à une température comprise entre 40°C et 60°C, de préférence entre 45 et 55°C. The extraction is generally carried out by immersing and gently shaking the white lily flowers in one or more of the solvents mentioned above for a period of between 1 and 6 hours, at a temperature of between 40°C and 60°C, preferably between 45 and 55°C.
L’étape d’extraction b) est suivie d’une filtration, par exemple sur un tamis de 50pm, pour éliminer les résidus végétaux. Extraction step b) is followed by filtration, for example on a 50 pm sieve, to eliminate plant residues.
Selon un mode préféré de réalisation, l’étape b) met en œuvre au moins deux extractions. Dans ce cas, chaque extraction étant suivie d’une étape de filtration. According to a preferred embodiment, step b) implements at least two extractions. In this case, each extraction is followed by a filtration step.
A l’issue de la ou des étapes d’extraction b), les filtrats liquides sont récupérés et mélangés. Le mélange de filtrat est ensuite laissé au repos pendant au moins 6h, de préférence au moins lOh. At the end of the extraction step(s) b), the liquid filtrates are recovered and mixed. The filtrate mixture is then left to stand for at least 6 hours, preferably at least 10 hours.
Le filtrat ou le mélange de filtrats obtenu à l’issue de l’étape c) est alors à nouveau filtré afin d’éliminer les substances insolubles : c’est l’étape d). De préférence, la filtration de l’extrait obtenu en c) est effectuée sur un tamis ou une membrane de filtration de 4 pm. On obtient ainsi un filtrat liquide. Enfin, le solvant présent dans le filtrat liquide est éliminé, et le reste de filtrat est dilué dans un autre solvant alcoolique (étape e)). The filtrate or mixture of filtrates obtained at the end of step c) is then filtered again in order to eliminate insoluble substances: this is step d). Preferably, the filtration of the extract obtained in c) is carried out on a sieve or a 4 μm filtration membrane. A liquid filtrate is thus obtained. Finally, the solvent present in the liquid filtrate is removed, and the remaining filtrate is diluted in another alcoholic solvent (step e)).
L’ordre des étapes de d’élimination du solvant et de la dilution du filtrat dans un autre solvant est indifférent. En particulier, le solvant présent dans le filtrat liquide peut être éliminé, puis le reste de filtrat est dilué dans un autre solvant alcoolique. Alternativement, le filtrat liquide est d’abord dilué dans un autre solvant alcoolique, et les solvants sont ensuite éliminés. Encore alternativement, la dilution du filtrat et l’élimination des solvants peut être simultanée. Le solvant alcoolique utilisé dans l’étape e) est appelé « autre solvant alcoolique », car il est différent du solvant alcoolique utilisé dans l’étape a). Tenant compte de cette limitation, le solvant alcoolique est typiquement choisi dans le même groupe que celui de l’étape a), i.e. parmi les monoalcools en C1-C4 et les diols.The order of the steps of removing the solvent and diluting the filtrate in another solvent is irrelevant. In particular, the solvent present in the liquid filtrate can be removed, then the remaining filtrate is diluted in another alcoholic solvent. Alternatively, the liquid filtrate is first diluted in another alcoholic solvent, and the solvents are then removed. Still alternatively, the dilution of the filtrate and the elimination of solvents can be simultaneous. The alcohol solvent used in step e) is called “other alcohol solvent” because it is different from the alcohol solvent used in step a). Taking this limitation into account, the alcoholic solvent is typically chosen from the same group as that of step a), i.e. from C1-C4 monoalcohols and diols.
De préférence, la dilution finale est réalisée dans un diol, de préférence du 1,3-propanediol. De préférence, l’élimination du solvant de l’étape e) se fait par évaporation, notamment par évaporation sous vide. Preferably, the final dilution is carried out in a diol, preferably 1,3-propanediol. Preferably, the elimination of the solvent from step e) is done by evaporation, in particular by evaporation under vacuum.
De préférence, entre les étapes d) et e), une étape de décoloration du filtrat obtenu en d) est ajoutée. La décoloration peut se faire par adsorption des pigments présents dans le filtrat sur charbon actif. Cette étape de décoloration peut être suivie d’une étape de filtration du filtrat décoloré obtenu, notamment jusqu’à Ipm. Preferably, between steps d) and e), a step of decolorization of the filtrate obtained in d) is added. Decolorization can be done by adsorption of the pigments present in the filtrate on activated carbon. This decolorization step can be followed by a filtration step of the decolorized filtrate obtained, in particular up to Ipm.
Préférentiellement, l’extrait alcoolique de fleurs de Lys blanc, Lilium candidum L, selon l’invention est susceptible d’être obtenu par un procédé comprenant les étapes suivantes : a) le broyage des fleurs de Lys blanc, Lilium candidum L., b) au moins une, de préférence au moins deux extractions desdites fleurs broyées en présence d’un solvant alcoolique, chaque extraction étant suivie d’une étape de filtration ; c) le mélange des au moins deux filtrats liquides issus des deux extractions de l’étape b) et repos du mélange obtenu pendant au moins 6h, de préférence au moins lOh ; d) filtration du mélange obtenu en c) pour obtenir un filtrat ; décoloration du filtrat obtenu en d) par adsorption sur charbon actif ; puis - filtration du filtrat décoloré sur une membrane de 1 pm ; et e) élimination de l’éthanol du filtrat obtenu par évaporation, puis dilution finale dans du 1,3-propanediol. Preferably, the alcoholic extract of white lily flowers, Lilium candidum L, according to the invention can be obtained by a process comprising the following steps: a) grinding the white lily flowers, Lilium candidum L., b ) at least one, preferably at least two extractions of said crushed flowers in the presence of an alcoholic solvent, each extraction being followed by a filtration step; c) mixing the at least two liquid filtrates resulting from the two extractions of step b) and resting the mixture obtained for at least 6 hours, preferably at least 1Oh; d) filtration of the mixture obtained in c) to obtain a filtrate; decolorization of the filtrate obtained in d) by adsorption on activated carbon; Then - filtration of the decolorized filtrate on a 1 μm membrane; and e) removal of ethanol from the filtrate obtained by evaporation, then final dilution in 1,3-propanediol.
Avantageusement, l’extrait mis en œuvre selon l’invention est de couleur claire.Advantageously, the extract used according to the invention is light in color.
Egalement, ledit extrait se présente sous une forme suffisamment concentrée pour pouvoir être utilisé sans entraîner les problèmes de formulation habituellement rencontrés aux concentrations nécessaires pour obtenir une activité dans les compositions cosmétiques ou dermatologiques sous forme d’émulsion, et sans présenter une couleur foncée, contrairement aux extraits végétaux obtenus par des procédés usuels, lorsqu’ils sont sous forme concentrée. Also, said extract is in a sufficiently concentrated form to be able to be used without causing the formulation problems usually encountered at the concentrations necessary to obtain activity in cosmetic or dermatological compositions in emulsion form, and without presenting a dark color, unlike to plant extracts obtained by usual processes, when they are in concentrated form.
En particulier, après évaporation de l’éthanol, l’extrait de fleurs de Lys blanc, Lilium candidum L., comprend 15 à 25% en poids d’extrait sec de Lys et 75 à 85% en poids de 1,3-propanediol, et de préférence, environ 20% en poids d’extrait sec de Lys et 80% en poids de 1,3-propanediol. In particular, after evaporation of the ethanol, the extract of white Lily flowers, Lilium candidum L., comprises 15 to 25% by weight of dry Lily extract and 75 to 85% by weight of 1,3-propanediol , and preferably, approximately 20% by weight of dry extract of Lys and 80% by weight of 1,3-propanediol.
De ce fait, l’extrait selon l’invention peut être utilisé directement pour la préparation d’une composition cosmétique. Therefore, the extract according to the invention can be used directly for the preparation of a cosmetic composition.
Selon un autre aspect, l’invention concerne l’utilisation cosmétique d’un extrait alcoolique de fleurs de Lys blanc, Lilium candidum L., selon l’invention, comme agent antioxydant et/ou anti-âge. According to another aspect, the invention relates to the cosmetic use of an alcoholic extract of white lily flowers, Lilium candidum L., according to the invention, as an antioxidant and/or anti-aging agent.
Selon encore un autre aspect, l’invention concerne l’utilisation cosmétique d’un extrait alcoolique de fleurs de Lys blanc, Lilium candidum L., selon l’invention, pour la prévention et/ou l’atténuation d’altérations de la peau dues au vieillissement. Et en particulier, en tant qu’ agent d’activation de la réponse au stress oxydatif médiée par NRF2 et/ou agent favorisant l’épaississement de l’épiderme. According to yet another aspect, the invention relates to the cosmetic use of an alcoholic extract of white lily flowers, Lilium candidum L., according to the invention, for the prevention and/or attenuation of alterations of the skin due to aging. And in particular, as an agent for activating the response to oxidative stress mediated by NRF2 and/or an agent promoting thickening of the epidermis.
En effet, de manière avantageuse, on a trouvé que l’extrait alcoolique de fleurs de Lys blanc, Lilium candidum L., selon l’invention possédait plusieurs activités d’intérêt vis- à-vis de mécanismes physiologiques préventifs ou réparateurs liés aux altérations de la peau, dues notamment au vieillissement. On a notamment trouvé, de manière avantageuse, que l’extrait alcoolique de fleurs de Lys blanc, Lilium candidum L, selon l’invention permettait une augmentation de l’expression des marqueurs papillaires CCRL1, NTN et PDPN ainsi qu’une diminution de l’expression des marqueurs réticulaires CDH2, CNN et MGP dans des fibroblastes réticulaires. Indeed, advantageously, it was found that the alcoholic extract of white lily flowers, Lilium candidum L., according to the invention possessed several activities of interest with regard to preventive or restorative physiological mechanisms linked to alterations. of the skin, particularly due to aging. It was notably found, advantageously, that the alcoholic extract of white lily flowers, Lilium candidum L, according to the invention allowed an increase in the expression of the papillary markers CCRL1, NTN and PDPN as well as a reduction in the expression of the reticular markers CDH2, CNN and MGP in reticular fibroblasts.
L’extrait selon l’invention présente permet, en outre d’améliorer la morphologie de l’épiderme, notamment en favorisant son épaississement dans des modèles de peaux âgées reconstruites avec des fibroblastes réticulaires. The extract according to the present invention also makes it possible to improve the morphology of the epidermis, in particular by promoting its thickening in models of aged skin reconstructed with reticular fibroblasts.
L‘ invention concerne également, selon encore un autre aspect, une composition cosmétique comprenant, dans un véhicule cosmétiquement acceptable, un extrait alcoolique de fleurs de Lys blanc, Lilium candidum L., selon l’invention. De préférence, ledit extrait est présent dans la composition cosmétique ou dermatologique à raison de 0,001 à 10% en poids, par rapport au poids total de la composition, en particulier à raison de 0,01 à 10% en poids, de préférence de 0,1 à 10% en poids. Ladite composition cosmétique peut notamment, être adaptée à une application par voie topique. The invention also relates, according to yet another aspect, to a cosmetic composition comprising, in a cosmetically acceptable vehicle, an alcoholic extract of white lily flowers, Lilium candidum L., according to the invention. Preferably, said extract is present in the cosmetic or dermatological composition in an amount of 0.001 to 10% by weight, relative to the total weight of the composition, in particular in an amount of 0.01 to 10% by weight, preferably 0 .1 to 10% by weight. Said cosmetic composition may in particular be adapted for topical application.
Avantageusement, ladite composition cosmétique peut se présenter sous la forme d’une poudre, d’une émulsion, d’une microémulsion, d’une nanoémulsion, d’une suspension, d’une solution d’une lotion, d’une crème, d’un gel aqueux ou hydroalcoolique, d’une mousse, d’un sérum, d’une solution ou d’une dispersion pour aérosol, ou d’une dispersion de vésicules lipidiques. Advantageously, said cosmetic composition can be in the form of a powder, an emulsion, a microemulsion, a nanoemulsion, a suspension, a solution of a lotion, a cream, an aqueous or hydroalcoholic gel, a foam, a serum, a solution or dispersion for aerosol, or a dispersion of lipid vesicles.
Dans le cas d’une émulsion, il peut s’agir d’une émulsion eau dans huile ou huile dans eau. In the case of an emulsion, it can be a water-in-oil or oil-in-water emulsion.
La composition cosmétique selon l’invention peut comprendre également un solvant choisi en fonction des différents ingrédients et de la forme d’administration. The cosmetic composition according to the invention may also comprise a solvent chosen according to the different ingredients and the form of administration.
A titre d’exemples, on peut citer l’eau (de préférence de l’eau déminéralisée ou des eaux florales), un alcool tel que l’éthanol. As examples, we can cite water (preferably demineralized water or floral waters), an alcohol such as ethanol.
Ladite composition cosmétique peut également comprendre, en outre de l’extrait selon l’invention, au moins un additif usuel dans le domaine, tel que par exemple au moins un composé choisi parmi un agent émollient ou humectant, un agent gélifiant et/ou épaississant, un agent tensioactif, une huile, un agent actif, un colorant, un conservateur, un agent antioxydant, un agent actif, une poudre organique ou inorganique, un filtre solaire et un parfum. Said cosmetic composition may also comprise, in addition to the extract according to the invention, at least one usual additive in the field, such as for example at least one compound chosen from an emollient or humectant agent, a gelling and/or thickening agent. , a surfactant, an oil, an active agent, a coloring, a preservative, a antioxidant agent, an active agent, an organic or inorganic powder, a sunscreen and a perfume.
- Un ou plusieurs agent(s) humectant(s), tels que les polyols (glycérine, diglycérine, le propylène glycol, le propanediol, le caprylyl glycol, le pentylène glycol, l’hexanediol), les sucres, les glycosaminoglycanes tels que l'acide hyaluronique et ses sels et esters ; et les polyquatemiums tel que le lipidure PMB - One or more humectant(s), such as polyols (glycerin, diglycerin, propylene glycol, propanediol, caprylyl glycol, pentylene glycol, hexanediol), sugars, glycosaminoglycans such as hyaluronic acid and its salts and esters; and polyquatemiums such as PMB lipid
Ledit agent humectant sera présent dans la composition à une teneur de l'ordre de 0,1 à 30%, de préférence 0,005 à 10% en poids total de la composition. Said humectant will be present in the composition at a content of the order of 0.1 to 30%, preferably 0.005 to 10% by total weight of the composition.
- Un ou plusieurs agent(s) émollient(s) qui peuvent être choisi(s) par exemple parmi les esters tels que les esters de jojoba, les esters d'acides gras et d'alcool gras (octyldodecyl myristate, triethylhexanoin, Dicaprylyl carbonate, Isostearyl isostearate, caprylic/capric triglyceride), les beurres tels que les beurres de karité (butyrospemum parkii butter extract, shea butter ethyl esters, commercialisés sous les noms de LIPEX SHEASOFT, LIPEX SHEA-U, LIPEX SHEA, LIPEX SHEALIGHT, LIPEX SHEA TRIS) ou de moringa (moringa oil/hydrogenated moringa oil esters), les cires (acacia decurrens flower wax & helianthus annuus cera seed seed wax, Cl 0-18 triglycerides), les huiles végétales, le phytosqualane, les alcanes (undecane, tridecane) - One or more emollient agent(s) which can be chosen for example from esters such as jojoba esters, esters of fatty acids and fatty alcohol (octyldodecyl myristate, triethylhexanoin, Dicaprylyl carbonate , Isostearyl isostearate, caprylic/capric triglyceride), butters such as shea butters (butyrospemum parkii butter extract, shea butter ethyl esters, marketed under the names LIPEX SHEASOFT, LIPEX SHEA-U, LIPEX SHEA, LIPEX SHEALIGHT, LIPEX SHEA TRIS) or moringa (moringa oil/hydrogenated moringa oil esters), waxes (acacia decurrens flower wax & helianthus annuus cera seed seed wax, Cl 0-18 triglycerides), vegetable oils, phytosqualane, alkanes (undecane, tridecane )
Ledit agent émollient sera présent dans la composition à une teneur de l'ordre de 0,1 à 30%, de préférence 0,5 à 10% en poids total de la composition. Said emollient agent will be present in the composition at a content of the order of 0.1 to 30%, preferably 0.5 to 10% by total weight of the composition.
- Un ou plusieurs agent(s) gélifiants(s) et/ou épaississant(s) de la phase aqueuse, choisi par exemple parmi les dérivés cellulosiques, gommes d'origine végétale (guar, caroube, alginates, carraghenanes, pectines), d'origine microbienne (xanthane), les argiles (laponite), les homo- et copolymères réticulés ou non, hydrophiles ou amphiphiles, d'acide acryloylméthylpropane sulfonique (AMPS) et/ou d'acrylamide et/ou d'acide acrylique et/ou de sels ou d'esters d'acide acrylique (commercialisés sous les noms ARISTOFLEX AVC, Aristoflex AVS, Aristoflex HMB, SIMULGEL NS, Simulgel EG, Simulgel 600, Simulgel 800, Pemulen, carbopol, Sepiplus 400, Seppimax zen, Sepiplus S, COSMEDIA SP)- One or more gelling agent(s) and/or thickener(s) of the aqueous phase, chosen for example from cellulose derivatives, gums of plant origin (guar, carob, alginates, carrageenans, pectins), d microbial origin (xanthan), clays (laponite), homo- and copolymers, crosslinked or not, hydrophilic or amphiphilic, of acryloylmethylpropane sulfonic acid (AMPS) and/or acrylamide and/or acrylic acid and/or salts or esters of acrylic acid (marketed under the names ARISTOFLEX AVC, Aristoflex AVS, Aristoflex HMB, SIMULGEL NS, Simulgel EG, Simulgel 600, Simulgel 800, Pemulen, carbopol, Sepiplus 400, Seppimax zen, Sepiplus S, COSMEDIA SP)
Ledit agent gélifiant et/ou épaississant sera présent dans la composition à une teneur de l'ordre de 0,1 à 10% en poids total de la composition. Said gelling and/or thickening agent will be present in the composition at a content of the order of 0.1 to 10% by total weight of the composition.
- Un ou plusieurs agent(s) tensioactif(s), notamment - One or more surfactant(s), in particular
*les tensioactifs anioniques tels que les isethionates, les taurates, les sarcosinates, les glycinates, les glutamates, les phosphates (C20-22 alkyl phosphate commercialisé sous le nom SENSANOV WR) *anionic surfactants such as isethionates, taurates, sarcosinates, glycinates, glutamates, phosphates (C20-22 alkyl phosphate marketed under the name SENSANOV WR)
* les tensioactifs amphotères tel que les dérivés de la bétaïne, les amphoacétates* amphoteric surfactants such as betaine derivatives, amphoacetates
* les tensioactifs non ioniques tel que les dérivés de polyglycérol, les dérivés de sucre (les dérivés de glucosides ou de xylosides commercialisés sous le nom MONTANOV 68, MONTANOV 202, Montanov 82, MONTANOV L, EASYNOV), les lecithines. * non-ionic surfactants such as polyglycerol derivatives, sugar derivatives (glucoside or xyloside derivatives marketed under the name MONTANOV 68, MONTANOV 202, Montanov 82, MONTANOV L, EASYNOV), lecithins.
Ledit agent tensioactif, sera présent dans une teneur de l’ordre de 0,1 à 15%, de préférence 0,5 à 10% en poids, par rapport au poids total de la composition. Said surfactant will be present in a content of the order of 0.1 to 15%, preferably 0.5 to 10% by weight, relative to the total weight of the composition.
- Un ou plusieurs agent(s) actif(s) d'origine naturelle, biotechnologique ou synthétique ayant une activité biologique et ayant une efficacité sur la peau via des sites biologiques, par exemple choisi parmi les vitamines tels que la vitamine C et ses dérivés (ascorbyl glucoside, 3-o-ethyl ascorbic acid, le tétraisopalmitate d'ascorbyle), la vitamine A et ses dérivés, la vitamine E et ses dérivés, la vitamine B3 ou Niacinamide, le panthénol, les oligo-éléments, l'allantoïne, l'adénosine, les peptides (Palmitoyl tetrapeptide-7, Palmitoyl Tripeptide-1, Palmitoyl Pentapeptide-4, Acetyl Dipeptide-1 Cetyl Ester, Acetyl Tetrapeptide-5 commercialisés sous le nom NP RIGIN, MATRIXYL 3000, IDEALIFT, EYESERYL), les extraits végétaux (glycyrrhiza glabra extract, centella asiatica leaf extract, secale cereale seed extract), les extraits de levures, les alpha hydroxyacides tels que l'acide glycolique ou lactique, l’acide tranexamique et ses dérivés tel que le cetyl tranexamique ester etc. - One or more active agent(s) of natural, biotechnological or synthetic origin having biological activity and having effectiveness on the skin via biological sites, for example chosen from vitamins such as vitamin C and its derivatives (ascorbyl glucoside, 3-o-ethyl ascorbic acid, ascorbyl tetraisopalmitate), vitamin A and its derivatives, vitamin E and its derivatives, vitamin B3 or Niacinamide, panthenol, trace elements, Allantoin , adenosine, peptides (Palmitoyl tetrapeptide-7, Palmitoyl Tripeptide-1, Palmitoyl Pentapeptide-4, Acetyl Dipeptide-1 Cetyl Ester, Acetyl Tetrapeptide-5 marketed under the name NP RIGIN, MATRIXYL 3000, IDEALIFT, EYESERYL), plant extracts (glycyrrhiza glabra extract, centella asiatica leaf extract, secale cereale seed extract), yeast extracts, alpha hydroxy acids such as glycolic or lactic acid, tranexamic acid and its derivatives such as cetyl tranexamic ester etc.
Ledit agent actif sera présent dans la composition à une teneur de l'ordre de 0,1 à 10% en poids total de la composition. Said active agent will be present in the composition at a content of the order of 0.1 to 10% by total weight of the composition.
D’autres additifs habituellement utilisés en cosmétique peuvent également être présents dans la composition selon l’invention, notamment des conservateurs, des agents antioxydants ou des parfums bien connus dans le domaine technique. Other additives usually used in cosmetics may also be present in the composition according to the invention, in particular preservatives, antioxidant agents or perfumes well known in the technical field.
L’homme du métier est en mesure de choisir, parmi l’ensemble de ces éventuels additifs, aussi bien la nature que la quantité de ceux qui seront ajoutés à la composition, de telle sorte que celle-ci conserve l’ensemble de ses propriétés. Those skilled in the art are able to choose, among all of these possible additives, both the nature and the quantity of those which will be added to the composition, such that it retains all of its properties. .
L’invention est illustrée de manière non limitative par les exemples ci-dessous. Exemple 1 : Préparation d’un extrait alcoolique de fleurs de Lys blanc, Lilium candidum selon l’invention
Figure imgf000013_0001
The invention is illustrated in a non-limiting manner by the examples below. Example 1: Preparation of an alcoholic extract of white lily flowers, Lilium candidum according to the invention
Figure imgf000013_0001
Un extrait alcoolique de fleurs de Lys blanc, Lilium candidum L., selon l’invention est préparé par un procédé comprenant les étapes suivantes : a) le broyage de 200g fleurs de Lys blanc, Lilium candidum L., en poudre b) Extraction de la poudre dans 2000g d’éthanol 96° sous agitation à 50°C pendant 2h ; An alcoholic extract of white lily flowers, Lilium candidum L., according to the invention is prepared by a process comprising the following steps: a) grinding 200g white lily flowers, Lilium candidum L., into powder b) Extraction of the powder in 2000g of 96° ethanol with stirring at 50°C for 2 hours;
Tamisage du mélange 1 obtenu à 50pm : le filtrat 1 est mis de côté ;Sieving of mixture 1 obtained at 50 pm: filtrate 1 is set aside;
Extraction des drêches dans 2000g d’éthanol 96° sous agitation à 50°C pendant 2h ; Extraction of spent grains in 2000g of 96° ethanol with stirring at 50°C for 2 hours;
Tamisage du mélange 2 obtenu à 50pm : les drêches sont écartées ; c) Ajout du filtrat 2 au filtrat 1 et décantation du mélange pendant une nuit ; d) Filtration du surnageant à 4pm ; Sieving of mixture 2 obtained at 50 pm: the spent grains are discarded; c) Adding filtrate 2 to filtrate 1 and decanting the mixture overnight; d) Filtration of the supernatant at 4 pm;
- Détermination de la matière sèche sur 3X5g d’extrait placé 3h à 110°C ; - Determination of dry matter on 3X5g of extract placed for 3 hours at 110°C;
- Décoloration du filtrat 3h à température ambiante sous agitation après ajout de 20% de charbon actif par rapport à l’extrait sec ; - Discoloration of the filtrate for 3 hours at room temperature with stirring after adding 20% of activated carbon relative to the dry extract;
- Filtrations sur membranes à 4 et Ipm : élimination du charbon actif ; e) Ajout de 180 g de 1,3 -propanediol et agitation une demi -heure ; et évaporation de l’éthanol à l’évaporateur rotatif. - Filtration on membranes at 4 and Ipm: elimination of activated carbon; e) Adding 180 g of 1,3-propanediol and stirring for half an hour; and evaporation of ethanol using a rotary evaporator.
Filtration finale à 4pm. Final filtration at 4pm.
Exemple 2 : Test des propriétés de l’extrait de Lys selon l’invention contre le stress oxydatif. Example 2: Test of the properties of the Lily extract according to the invention against oxidative stress.
Protocole : Des kératinocytes épidermiques humains normaux issus de deux donneurs juvéniles ont été ensemencés en plaque 6 puits et cultivés en milieu complémenté KGM2 (Lonza) pendant 72h à 37°C et 5% de CO2. Les cellules ont ensuite été incubées ou non (condition non traitée) avec 0,25% d’extrait pendant 24h. Chaque condition a été effectuée en duplicat. Les ARNs totaux ont été extraits à l'aide du kit RNeasy 96 Plate Extraction Kit (Qiagen) selon les recommandations du fournisseur. La quantité et la qualité des ARNs ont été évaluées par Multiskan GO (Thermo Fischer). Les ADN complémentaires ont été synthétisés et un transcriptome a été réalisé sur puce Affymetrix GeneChip Human Transcriptome Array 2.0. L'analyse bioinformatique des gènes dont l'expression est modulée a minima par un facteur 2 (FC : fold change, niveau d’expression vs condition non traitée) a été effectuée avec le logiciel Ingenuity Pathway Analysis (IP A®, QIAGEN). Protocol: Normal human epidermal keratinocytes from two juvenile donors were seeded in a 6-well plate and cultured in supplemented KGM2 medium (Lonza) for 72 hours at 37°C and 5% CO2. The cells have then incubated or not (untreated condition) with 0.25% extract for 24 hours. Each condition was performed in duplicate. Total RNA was extracted using the RNeasy 96 Plate Extraction Kit (Qiagen) according to the supplier's recommendations. The quantity and quality of sRNAs were evaluated by Multiskan GO (Thermo Fischer). The complementary DNAs were synthesized and a transcriptome was produced on an Affymetrix GeneChip Human Transcriptome Array 2.0 chip. The bioinformatics analysis of genes whose expression is modulated at least by a factor of 2 (FC: fold change, expression level vs. untreated condition) was carried out with the Ingenuity Pathway Analysis software (IP A®, QIAGEN).
Résultats : à 0,25%, l’extrait est capable de moduler en moyenne l’expression de 158 gènes (dont 59 inhibés et 99 stimulés) dans des kératinocytes humains normaux après 24h de traitement. Results: at 0.25%, the extract is capable of modulating on average the expression of 158 genes (including 59 inhibited and 99 stimulated) in normal human keratinocytes after 24 hours of treatment.
Le logiciel IP A a été utilisé pour évaluer les modifications de l’activité biologique après traitement avec l’extrait. Une carte représentant la modulation de l’expression de différentes voies biologiques a été établie (données non fournies). La carte transcriptomique obtenue après 24h de traitement révèle la modulation de nombreuses fonctions biologiques avec 0,25% d’extrait. Le Lys de la Madone est notamment capable de moduler 64 voies de signalisation canoniques. IP A software was used to evaluate changes in biological activity after treatment with the extract. A map representing the modulation of the expression of different biological pathways was established (data not provided). The transcriptomic map obtained after 24 hours of treatment reveals the modulation of numerous biological functions with 0.25% extract. The Madonna Lily is notably capable of modulating 64 canonical signaling pathways.
Parmi les voies biologiques significativement activées par l’extrait de lys à 0,25%, on retrouve la voie de réponse au stress oxydatif médiée par NRF2 (nuclear factor erythroid 2-related factor 2, facteur nucléaire 2 lié au facteur érythroïde 2). NRF2 est un facteur de transcription qui permet, une fois activé, d’augmenter l’expression d’enzymes antioxydantes telles que GCLM, GPX, GST, NQO1, SOD et TXNR. NRF2 active également la transcription de protéines antioxydantes non enzymatiques comme la ferritine composée notamment des sous-unités FTL et FTH1. La stimulation de cette voie biologique de détoxification cellulaire globale dans des kératinocytes normaux après 24h de traitement par l’extrait à 0,25% lui confère des propriétés antioxydantes et anti-âge, le stress oxydatif participant au vieillissement de la peau. Among the biological pathways significantly activated by 0.25% lily extract, we find the oxidative stress response pathway mediated by NRF2 (nuclear factor erythroid 2-related factor 2). NRF2 is a transcription factor which, once activated, increases the expression of antioxidant enzymes such as GCLM, GPX, GST, NQO1, SOD and TXNR. NRF2 also activates the transcription of non-enzymatic antioxidant proteins such as ferritin, composed in particular of the FTL and FTH1 subunits. The stimulation of this biological pathway of global cellular detoxification in normal keratinocytes after 24 hours of treatment with the 0.25% extract gives it antioxidant and anti-aging properties, as oxidative stress contributes to skin aging.
Tableau I : Liste des gènes impliqués dans la voie biologique de « réponse au stress oxydatif médiée par NRF2 » dont l’expression est significativement stimulée par l'extrait de Lys à 0,25%. NRF2 : Facteur nucléaire 2 lié au facteur érythroïde 2, FC : niveau d’expression vs condition non traitée
Figure imgf000015_0001
Table I: List of genes involved in the biological pathway of “NRF2-mediated oxidative stress response” whose expression is significantly stimulated by the extract of Lys at 0.25%. NRF2: Nuclear factor 2 related to factor erythroid 2, FC: expression level vs untreated condition
Figure imgf000015_0001
5 Exemple 3 : Propriétés anti-âge de l’extrait de Lys selon l’invention dans des modèles cellulaires et tissulaires de vieillissement cutané. 5 Example 3: Anti-aging properties of the Lily extract according to the invention in cellular and tissue models of skin aging.
Au niveau cellulaire, le derme peut être divisé en deux sous-populations de fibroblastes : les fibroblastes papillaires, situés sous l’épiderme au niveau des papilles et qui présentent un phénotype plus jeune, et les fibroblastes réticulaires, plusAt the cellular level, the dermis can be divided into two subpopulations of fibroblasts: papillary fibroblasts, located under the epidermis at the level of the papillae and which present a younger phenotype, and reticular fibroblasts, more
10 en profondeur et plus différenciés montrant un phénotype plus âgé. Ces deux sous- populations expriment des marqueurs spécifiques : CCRL1, NTN et PDPN pour les fibroblastes papillaires et CDH2, CNN et MGP pour les fibroblastes réticulaires. Le vieillissement du derme se caractérise notamment par la différenciation progressive des fibroblastes papillaires en fibroblastes réticulaires conduisant à une rigidification du10 in depth and more differentiated showing an older phenotype. These two subpopulations express specific markers: CCRL1, NTN and PDPN for papillary fibroblasts and CDH2, CNN and MGP for reticular fibroblasts. Aging of the dermis is characterized in particular by the progressive differentiation of papillary fibroblasts into reticular fibroblasts leading to stiffening of the
15 derme. Ce vieillissement peut être modélisé en laboratoire, au niveau cellulaire, en utilisant des fibroblastes réticulaires et, au niveau tissulaire, en reconstruisant des peaux équivalentes avec un derme synthétisé par des fibroblastes réticulaires. Ces modèles peuvent être ainsi utilisés pour identifier des ingrédients aux propriétés anti-âge capables de reverser le vieillissement dermique. 15 dermis. This aging can be modeled in the laboratory, at the cellular level, using reticular fibroblasts and, at the tissue level, by reconstructing equivalent skin with a dermis synthesized by reticular fibroblasts. These models can thus be used to identify ingredients with anti-aging properties capable of reversing dermal aging.
20 Protocole modèle cellulaire : Des fibroblastes réticulaires dermiques humains normaux issus de trois donneurs ont été ensemencés en plaque 6 puits et cultivés en milieu DMEM supplémenté avec 5% de sérum pendant 72h à 37°C et 5% de CO2. Les cellules ont ensuite été incubées ou non (condition non traitée) avec 0,25% d’extrait pendant 96h dans un milieu DMEM supplémenté avec 2,5% de sérum. Les ARNs totaux ont été extraits à l'aide du kit RNeasy 96 Plate Extraction Kit (Qiagen) selon les recommandations du fournisseur. La quantité et la qualité des ARNs ont été évaluées par Experion (Biorad). Les ADN complémentaires ont été synthétisés (iScript kit, Biorad) puis les réactions de qPCR ont été réalisées avec la méthode SYBR Green (Biorad) suivant ce programme : 5 min à 95°C puis 35 cycles avec 20 secondes à 95°C, 20 secondes à 60°C et 20 secondes à 72°C suivis par la génération de courbes de fusion. Les analyses d’expression ont été réalisées avec le logiciel iQ5 (Biorad) en utilisant la méthode des AACt avec des gènes de référence exprimés de façon stable. L’expression de biomarqueurs spécifiques des fibroblastes papillaires (CCRL1, NTN et PDPN) et réticulaires (CDH2, CNN et MGP) a ainsi été évaluée dans les échantillons. 20 Cell model protocol: Normal human dermal reticular fibroblasts from three donors were seeded in a 6-well plate and cultured in DMEM medium supplemented with 5% serum for 72 hours at 37°C and 5% CO2. The cells were then incubated or not (untreated condition) with 0.25% extract for 96 h in DMEM medium supplemented with 2.5% serum. THE Total RNAs were extracted using the RNeasy 96 Plate Extraction Kit (Qiagen) according to the supplier's recommendations. The quantity and quality of sRNAs were assessed by Experion (Biorad). The complementary DNAs were synthesized (iScript kit, Biorad) then the qPCR reactions were carried out with the SYBR Green method (Biorad) following this program: 5 min at 95°C then 35 cycles with 20 seconds at 95°C, 20 seconds at 60°C and 20 seconds at 72°C followed by the generation of melting curves. Expression analyzes were carried out with iQ5 software (Biorad) using the AACt method with stably expressed reference genes. The expression of biomarkers specific to papillary (CCRL1, NTN and PDPN) and reticular (CDH2, CNN and MGP) fibroblasts was thus evaluated in the samples.
Résultats : Comme indiqué dans la Figure 1, à 0,25%, l’extrait est capable d’augmenter l’expression des marqueurs papillaires CCRL1, NTN et PDPN ainsi que de diminuer l’expression des marqueurs réticulaires CDH2, CNN et MGP dans des fibroblastes réticulaires après 96h de traitement. L’extrait de Lys présente donc une capacité à reverser le phénotype âgé des fibroblastes réticulaires en un phénotype plus jeune, proche de celui des fibroblastes papillaires. Results: As shown in Figure 1, at 0.25%, the extract is able to increase the expression of papillary markers CCRL1, NTN and PDPN as well as decrease the expression of reticular markers CDH2, CNN and MGP in reticular fibroblasts after 96 hours of treatment. Lys extract therefore has the capacity to reverse the aged phenotype of reticular fibroblasts into a younger phenotype, close to that of papillary fibroblasts.
Protocole modèle tissulaire : Des fibroblastes papillaires ou réticulaires dermiques humains normaux issus de trois donneurs ont été ensemencés et cultivés en milieu DMEM supplémenté avec 5% de sérum (HyClone) pendant 5 jours à 37°C et 5% de CO2. Les cellules ont ensuite été incubées ou non (condition contrôle) avec 0,25% d’extrait ou avec 0,25% de solvant propandiol (condition diluant seul) pendant 4 jours. Des dermes équivalents ont été générés avec les cellules traitées ou contrôles puis ils ont été incubés de nouveau ou non avec 0,25% d’extrait de Lys ou de propandiol en milieu DMEM supplémenté avec 5% de sérum et 1% de pénicilline-streptomycine (Invitrogen) à 37°C et 5% de CO2, pendant 7 jours. Des kératinocytes épidermiques humains normaux ont ensuite été ensemencés sur les dermes équivalents et les cultures maintenues en milieu DMEM/Ham’s F 12 (3 : 1) supplémenté avec 5% de sérum, 1.1 pM hydrocortisone, 1 pM d’ isoproterenol, 0.1 pM d’insuline (Sigma-Aldrich) et 1% de pénicilline-streptomycine (Invitrogen), pendant 2 jours. Les peaux reconstruites avec des fibroblastes papillaires (Pap) ou réticulaires (Ret) ont été placées à l’interface air/liquide et de nouveau traitées ou non selon les conditions précédemment décrites pendant 14 jours avant d’être fixées, déshydratées puis incluses en paraffine. Des coupes histologiques ont ensuite été réalisées et utilisées pour une coloration hématoxyline safran éosine (HSE) ou un immunomarquage Ki67. Tissue model protocol: Normal human papillary or reticular dermal fibroblasts from three donors were seeded and cultured in DMEM medium supplemented with 5% serum (HyClone) for 5 days at 37°C and 5% CO2. The cells were then incubated or not (control condition) with 0.25% extract or with 0.25% propandiol solvent (diluent only condition) for 4 days. Equivalent dermis were generated with the treated or control cells then they were incubated again or not with 0.25% Lys extract or propandiol in DMEM medium supplemented with 5% serum and 1% penicillin-streptomycin (Invitrogen) at 37°C and 5% CO2, for 7 days. Normal human epidermal keratinocytes were then seeded on the equivalent dermis and the cultures maintained in DMEM/Ham's F 12 (3:1) medium supplemented with 5% serum, 1.1 pM hydrocortisone, 1 pM isoproterenol, 0.1 pM insulin (Sigma-Aldrich) and 1% penicillin-streptomycin (Invitrogen), for 2 days. The skins reconstructed with papillary (Pap) or reticular (Ret) fibroblasts were placed at the air/liquid interface and again treated or not according to the conditions previously described. for 14 days before being fixed, dehydrated and then embedded in paraffin. Histological sections were then made and used for hematoxylin saffron eosin (HSE) staining or Ki67 immunostaining.
La coloration hématoxyline safran éosine (HSE) a été réalisée afin d’observer leur morphologie globale et notamment l’épaisseur de l’épiderme qui s’affine dans les modèles de peaux âgées réticulaires ( s peaux « jeunes » papillaires)6. Un immunomarquage de Ki67, un marqueur de la prolifération cellulaire, a aussi été réalisé afin de dénombrer les cellules positives dans les peaux reconstruites avec des fibroblastes papillaires. Un démasquage antigénique a été effectué en tampon citrate à pH6, avant incubation dans une solution de blocage empêchant la fixation aspécifique des anticorps. Les coupes sont ensuite incubées sur la nuit à 4°C avec un anticorps primaire ciblant spécifiquement Ki67 (MIB-1, Dako) puis avec le système avidine- biotine-peroxydase en suivant les recommandations du fournisseur (GE Healthcare). Le marquage a été visualisé par ajout d’AEC (3-amino-9-ethylcarbazole) et les coupes ont été contre-colorées à l’aide d’ hématoxyline. Hematoxylin saffron eosin (HSE) staining was carried out in order to observe their overall morphology and in particular the thickness of the epidermis which becomes thinner in reticular aged skin models (“young” papillary skin) 6 . Immunostaining for Ki67, a marker of cell proliferation, was also carried out to count positive cells in skin reconstructed with papillary fibroblasts. Antigenic unmasking was carried out in citrate buffer at pH6, before incubation in a blocking solution preventing nonspecific binding of the antibodies. The sections are then incubated overnight at 4°C with a primary antibody specifically targeting Ki67 (MIB-1, Dako) then with the avidin-biotin-peroxidase system following the supplier's recommendations (GE Healthcare). The marking was visualized by adding AEC (3-amino-9-ethylcarbazole) and the sections were counterstained using hematoxylin.
Résultats : Comme le montre la Figure 2, à 0,25%, l’extrait de Lys selon l’invention est capable d’améliorer la morphologie de l’épiderme, notamment en favorisant son épaississement (à droite), dans des modèles de peaux âgées reconstruites avec des fibroblastes réticulaires par rapport aux conditions non traitées (au centre). Les peaux traitées avec l’extrait retrouvent ainsi une morphologie plus jeune, proche de celles obtenues avec des peaux reconstruites avec des fibroblastes papillaires non traitées (à gauche). Results: As shown in Figure 2, at 0.25%, the Lily extract according to the invention is capable of improving the morphology of the epidermis, in particular by promoting its thickening (right), in models of aged skin reconstructed with reticular fibroblasts compared to untreated conditions (center). The skin treated with the extract thus regains a younger morphology, close to that obtained with skin reconstructed with untreated papillary fibroblasts (left).
Comme indiqué dans la Figure 3, à 0,25%, l’extrait est également capable d’augmenter le nombre de cellules exprimant le marqueur de prolifération Ki67 dans la couche basale des peaux reconstruites avec des fibroblastes papillaires. Il favorise donc le renouvellement cellulaire. As shown in Figure 3, at 0.25%, the extract is also capable of increasing the number of cells expressing the proliferation marker Ki67 in the basal layer of skin reconstructed with papillary fibroblasts. It therefore promotes cell renewal.
Ainsi, l’extrait de Lys à 0,25% est capable de ralentir le vieillissement dermique en modifiant un phénotype réticulaire en un phénotype papillaire plus jeune dans des modèles cellulaires et tissulaires. Il présente donc de fortes propriétés anti-âge. Exemple 4 : compositions cosmétiques Thus, 0.25% Lys extract is capable of slowing down dermal aging by modifying a reticular phenotype into a younger papillary phenotype in cellular and tissue models. It therefore has strong anti-aging properties. Example 4: cosmetic compositions
Les compositions suivantes peuvent être préparées de façon classique pour l'homme du métier. Les quantités indiquées ci-dessous sont exprimées en pourcentages pondéraux. Les ingrédients en majuscules sont identifiés conformément à la dénomination INCI. The following compositions can be prepared in a conventional manner for those skilled in the art. The quantities indicated below are expressed as percentages by weight. Ingredients in capital letters are identified in accordance with the INCI name.
A — émulsion huile/eau gel
Figure imgf000018_0001
Figure imgf000019_0001
A — oil/water gel emulsion
Figure imgf000018_0001
Figure imgf000019_0001
b — émulsion huile/eau crème
Figure imgf000020_0001
b — oil/water cream emulsion
Figure imgf000020_0001
Ces compositions peuvent être appliquées tous les jours, matin et/ou soir, sur la peau. These compositions can be applied every day, morning and/or evening, to the skin.

Claims

REVENDICATIONS Extrait alcoolique de fleurs de Lys blanc, Liiïum candidum L., comprenant au moins de lilidine glycoside et de l’acide hopanténique. Extrait alcoolique de fleurs Lys blanc selon la revendication 1, comprenant CLAIMS Alcoholic extract of white lily flowers, Liiïum candidum L., comprising at least lilidine glycoside and hopantenic acid. Alcoholic extract of white lily flowers according to claim 1, comprising
- 40 à 70% en poids de saccharides, de préférence 50 à 60% en poids,- 40 to 70% by weight of saccharides, preferably 50 to 60% by weight,
- 1 à 5% en poids de composés dérivés du kaempferol di-0 et tri-O- glycosylé, de préférence 2,5 à 3,2% en poids, - 1 to 5% by weight of compounds derived from di-0 and tri-O-glycosylated kaempferol, preferably 2.5 to 3.2% by weight,
- 8 à 15% en poids de lilidine glycoside, de préférence 10 à 13% en poids, et- 8 to 15% by weight of lilidine glycoside, preferably 10 to 13% by weight, and
- 1 à 5% en poids d’acide hopanténique, de préférence 2 à 3% en poids, les pourcentages étant exprimés en poids, par rapport au poids total de l’extrait. Extrait alcoolique de fleurs de Lys blanc selon l’une quelconque des revendications précédentes, dans lequel les saccharides comprennent du glucose, du fructose et/ou du sucrose, de préférence 20 à 25% en poids de fructose, 17 à 21% en poids de glucose et 5 à 11% en poids de sucrose. Procédé d’extraction des fleurs de Lys blanc, Lilium candidum L, comprenant les étapes suivantes : a) le broyage des fleurs de Lys blanc, Lilium candidum L. L., b) au moins une, de préférence au moins deux extractions desdites fleurs broyées en présence d’un solvant alcoolique, chaque extraction étant suivie d’une étape de filtration ; c) le mélange des filtrats liquides issus des extractions de l’étape b) et repos du mélange obtenu pendant au moins 6h, de préférence au moins lOh ; d) filtration du mélange obtenu en c) ; e) élimination du solvant mono-alcoolique du mélange obtenu en d), puis et dilution finale dans un autre solvant alcoolique. Procédé selon la revendication 4, caractérisé en ce que les fleurs de Lys blanc mises en œuvre à l’étape a) sont des fleurs fraîches ou des fleurs séchées. Procédé selon la revendication 4 ou 5, caractérisé en ce qu’à l’étape a), les fleurs de Lys blanc sont broyées à une finesse inférieure à 2 cm. Procédé selon l’une quelconque des revendications 4 à 6, caractérisé en ce que le solvant alcoolique de l’étape b) est un monoalcool comprenant de 1 à 4 atomes de carbone, de préférence l’éthanol. Procédé selon l’une quelconque des revendications 4 à 7, caractérisé en ce que les extractions de l’étape b) sont réalisées pendant une durée comprise entre 1 et 6 heures, à une température comprise entre 40°C et 60°C, de préférence entre 45 et 55°C. Procédé selon l’une quelconque des revendications 4 à 8, caractérisé en ce que chaque extraction de l’étape b) est suivie d’une filtration sur un tamis de 50pm. Procédé selon l’une quelconque des revendications 4 à 9, caractérisé en ce que le filtration mise en œuvre à l’étape d) est réalisée sur un tamis ou une membrane de filtration de 4pm. Procédé selon la revendication 4 à 10, caractérisé en ce que, entre les étapes d) et e), est ajoutée une étape de décoloration du filtrat obtenu en d), de préférence par adsorption sur charbon actif, suivie d’une étape de filtration du filtrat décoloré obtenu, de préférence jusqu’à Ipm. Procédé selon la revendication 4 à 11, caractérisé en ce que l’élimination de l’étape e) se fait par évaporation, puis la dilution finale est réalisée dans du 1,3- propanediol. - 1 to 5% by weight of hopantenic acid, preferably 2 to 3% by weight, the percentages being expressed by weight, relative to the total weight of the extract. Alcoholic extract of white lily flowers according to any one of the preceding claims, in which the saccharides comprise glucose, fructose and/or sucrose, preferably 20 to 25% by weight of fructose, 17 to 21% by weight of glucose and 5 to 11% by weight of sucrose. Process for extracting white lily flowers, Lilium candidum L, comprising the following steps: a) grinding white lily flowers, Lilium candidum LL, b) at least one, preferably at least two extractions of said crushed flowers in the presence an alcoholic solvent, each extraction being followed by a filtration step; c) mixing the liquid filtrates resulting from the extractions of step b) and resting the mixture obtained for at least 6 hours, preferably at least 1Oh; d) filtration of the mixture obtained in c); e) elimination of the mono-alcoholic solvent from the mixture obtained in d), then and final dilution in another alcoholic solvent. Method according to claim 4, characterized in that the white lily flowers used in step a) are fresh flowers or dried flowers. Method according to claim 4 or 5, characterized in that in step a), the white lily flowers are crushed to a fineness of less than 2 cm. Process according to any one of claims 4 to 6, characterized in that the alcoholic solvent of step b) is a monoalcohol comprising from 1 to 4 carbon atoms, preferably ethanol. Method according to any one of claims 4 to 7, characterized in that the extractions of step b) are carried out for a period of between 1 and 6 hours, at a temperature of between 40°C and 60°C, of preferably between 45 and 55°C. Method according to any one of claims 4 to 8, characterized in that each extraction of step b) is followed by filtration on a 50 pm sieve. Method according to any one of claims 4 to 9, characterized in that the filtration carried out in step d) is carried out on a sieve or a 4 pm filtration membrane. Process according to claims 4 to 10, characterized in that, between steps d) and e), a step of decolorization of the filtrate obtained in d), preferably by adsorption on activated carbon, is added, followed by a filtration step of the decolorized filtrate obtained, preferably up to Ipm. Process according to claims 4 to 11, characterized in that the elimination of step e) is done by evaporation, then the final dilution is carried out in 1,3-propanediol.
13. Extrait alcoolique de fleurs de Lys blanc, Liiïum candidum L., caractérisé en ce qu’il est susceptible d’être obtenu par un procédé selon l’une quelconque des revendications 4 à 12. 14. Utilisation cosmétique d’un extrait alcoolique de fleurs de Lys blanc, Lilium candidum L, selon l’une quelconque des revendications 1 à 3, comme antioxydant, et/ou pour la prévention et/ou l’atténuation d’altérations de la peau dues au vieillissement et/ou comme agent d’activation de la réponse au stress oxydatif médiée par NRF2 et/ou agent favorisant l’épaississement de l’épiderme. 13. Alcoholic extract of white lily flowers, Liiïum candidum L., characterized in that it can be obtained by a process according to any one of claims 4 to 12. 14. Cosmetic use of an alcoholic extract white lily flowers, Lilium candidum L, according to any one of claims 1 to 3, as an antioxidant, and/or for the prevention and/or attenuation of changes to the skin due to aging and/or as an agent activation of the response to oxidative stress mediated by NRF2 and/or agent promoting thickening of the epidermis.
15. Composition cosmétique comprenant, dans un véhicule cosmétiquement acceptable, un extrait alcoolique de fleurs de Lys blanc, Lilium candidum L., selon l’une quelconque des revendications 1 à 3. 15. Cosmetic composition comprising, in a cosmetically acceptable vehicle, an alcoholic extract of white lily flowers, Lilium candidum L., according to any one of claims 1 to 3.
PCT/EP2023/077617 2022-10-05 2023-10-05 Alcoholic extract of white lily flowers lilium candidum l, method for obtaining same, and cosmetic composition containing same WO2024074633A1 (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120156266A1 (en) * 2010-12-17 2012-06-21 Chong Jin Loy Compositions comprising lilium candidum extracts and uses thereof
FR3026946A1 (en) * 2014-10-08 2016-04-15 Laboratoires De Biologie Vegetale Yves Rocher COSMETIC USE OF LILIUM CANDIDUM EXTRACT AS ANTI-REDNESS AGENT AND / OR TO ENHANCE SKIN SLIMMING

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US20120156266A1 (en) * 2010-12-17 2012-06-21 Chong Jin Loy Compositions comprising lilium candidum extracts and uses thereof
FR3026946A1 (en) * 2014-10-08 2016-04-15 Laboratoires De Biologie Vegetale Yves Rocher COSMETIC USE OF LILIUM CANDIDUM EXTRACT AS ANTI-REDNESS AGENT AND / OR TO ENHANCE SKIN SLIMMING

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