Cosmetic composition and treatment for treating sagging skin
By stimulating fibroblasts to produce elastin by using extracts from the genus genus genus stimulating fibroblasts, the problems of skin sagging and reducing elasticity are solved, and the firmness and aesthetics of the skin are significantly improved.
Patent Information
- Application Number
- CN202180019464.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2020-03-20
- Filing Date
- 2021-03-18
- Publication Date
- 2025-01-07
- Estimated Expiration
- 2041-03-18
AI Technical Summary
Skin aging leads to loose skin and lacks elasticity and firmness, and the prior art is difficult to effectively solve this problem.
The extract of the genus Yellow Bruce, especially the leaf extract of the genus Yellow Bruce, is used to stimulate fibroblasts to produce elastin and fibers, strengthen the outer skin matrix, and improve the elasticity and firmness of the skin.
Significantly improves the elastic properties of facial and body skin, reduces wrinkles and depressions, and enhances the overall firmness and aesthetics of the skin.
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Abstract
Description
Technical Field
[0001] The present invention relates to cosmetic compositions and treatments for treating skin sagging. It is particularly aimed at the cosmetic, dermatological and hygiene and personal care product industries. Background Art
[0002] Chronological aging or intrinsic aging varies from one individual to another, because aging is very strongly related to the genetic inheritance of the individual, which (for example, the conditions for the production of protective pigments) manages antioxidants and immune defenses or even determines the timing of menopause. Another type of aging covers the first one. It is induced by frequent sun exposure, environmental pollutants, our diet containing too much sugar and / or fat, and our lifestyle (stress, less rest time, significant and / or too rapid weight loss, pregnancy, breastfeeding, etc.). It is also highly variable from one individual to another.
[0003] During skin aging, the face and body change and lose their coordination. The skin thins and becomes increasingly stretched (sagging or loose skin). The skin is less elastic, less firm and less smooth (wrinkle effect). The skin does not easily regain its shape when stretched because it loses its elasticity. The skin sags under its own weight (ptosis). On the face, this results in the oval or less defined contours of the face, dewlap on the jowls and / or drooping eyelids, and the formation of unsightly wrinkles such as, for example, wrinkles on the eyelids (see Figure 1 ) or wrinkles on the sides of the mouth (also called perioral "marionette lines", see Figure 2 ). Other parts of the body may also be affected, such as the neck below the jaw, under the arms, lower abdomen, or between the breasts.
[0004] At the skin composition level, elasticity changes during aging due to a decrease in the amount of elastin produced and also due to a disruption of the elastic fiber network.
[0005] In the extracellular matrix, elastic fibers are composed of elastin and microtubules. They appear in the form of a dense and closely connected network in young people. Therefore, they provide the skin with resilience and elasticity. Elastin is the dominant component of elastic fibers (90%), which is produced in an immature form called tropoelastin. Tropoelastin self-assembles on a pre-established scaffold of microfibrils composed of myofibrillin, which is assembled and maintained with the help of the protein MFAP4 (microfibrillin-associated protein 4). This protein decreases in aging skin and is therefore crucial. Another protein, fibrillin-5, is also involved in the construction of this scaffold.
[0006] Dermis-epidermis junction (DEJ) is the key part of skin, because it ensures the adhesion between epidermis structure and dermis and epidermis.During aging, the synthetic reduction of its components (especially collagen IV, VII and laminin V) and the flattening of DEJ are observed very clearly in menopausal skin.This weakening effect occurs by protease to the adverse effect of the hemidesmosomes of the albumen (collagen IV, VII and laminin V) by which the keratinocytes of epidermis are connected to DEJ.Therefore, the aging of DEJ also has a significant impact on the resilience of skin and the loss of its vitality. Summary of the invention
[0007] The object of the present invention is to provide a solution to skin sagging associated with defects (in quality and / or in quantity) of elastin and elastic fibers.
[0008] For this purpose, the present invention provides the use of a plant extract of the genus Engelhardtia for the non-therapeutic cosmetic treatment of sagging skin. In particular, facial features or lines are re-harmonized with the help of the treatment according to the invention.
[0009] The genus Engelhardtia includes in particular the following species: Engelhardtia chrysolepsis Hance (synonym: Engelhardtia roxburghiana Lindl), Engelhardtia apoensis Elmer ex Nagel, Engelhardtia hainanensis PYChen, Engelhardtia mendalomensis EJF Campb., Engelhardtia mersingensis EJF Campb., Engelhardtia rigida Blume, Engelhardtia mollis Hu, Engelhardtia serrata Blume, Engelhardtia spicata Lechen ex Blume, Engelhardtia spicata var. integra (Kurz) WE Manning ex Steenis and Engelhardtia unijuga (Chun) Chun ex PYChen.
[0010] Preferably, the present invention is directed to the use of extracts of the species Lycopodiella ciliata.
[0011] Huang qui is a subtropical plant known in Asia for centuries and possibly thousands of years. Its leaves are sold freely and used as a herbal tea in China (Huang qui) and Japan, with a slightly sweet taste, under the name Kohki tea in Japan.
[0012] The drink is appreciated for its soothing, detoxifying and medicinal benefits, particularly for the treatment of diabetes and hyperlipidemia, and for reducing fever.
[0013] Other preferred features according to the present invention are:
[0014] - the extract is obtained from leaves; and / or
[0015] - the extraction is achieved using an alcoholic solvent, preferably ethanol; and / or
[0016] - The extract is mixed with a physiologically acceptable medium, the extract is preferably dry, and diluted in the physiologically acceptable medium.
[0017] In vitro test results are given below in the description. They show the effectiveness of the cosmetic treatment according to the invention, which comes especially from:
[0018] - Stimulates fibroblasts to produce elastin;
[0019] - Increase the quantity and network quality of elastic fibers produced by fibroblasts;
[0020] - Increase the contractility of fibroblasts; and
[0021] - Strengthens DEJ in keratinocytes and skin explants.
[0022] The treatment according to the invention is therefore suitable for increasing the elastin synthesis of the extracellular matrix, improving the elastic fiber quantity and the quality of the network.
[0023] In addition, in vivo tests carried out on a group of volunteers whose facial skin quality was affected by aging showed the effectiveness of the cosmetic treatment according to the invention in improving skin sagging:
[0024] - Improve the elastic properties of facial skin;
[0025] - Improve facial features (contours, dewlap);
[0026] - Reduce the depth and volume of eyelid wrinkles;
[0027] - Reduce marionette lines along the mouth contour; and
[0028] - Reduce roughness and pit depth (pit smoothing).
[0029] The treatment according to the invention is advantageously a restorative treatment, reducing dewlap and ptosis of the eyelids, and the corresponding skin wrinkles.
[0030] The extracts according to the invention are of particular interest for use in premenopausal or postmenopausal women who experience a drop in estrogen which accelerates skin aging.
[0031] The present invention also provides a cosmetic composition comprising an alcohol extract of leaves from the genus Fructus Lysimachiae (preferably Fructus Lysimachiae) in a physiologically acceptable medium. The composition according to the invention can be more or less concentrated Fructus Lysimachiae extract, thereby forming a cosmetic ingredient or a final cosmetic preparation intended for consumers that can be prepared from the cosmetic ingredient. The composition according to the invention encompasses a dry extract content of about 0.0001%-10% relative to the total weight of the composition.
[0032] Preferably, the alcoholic extract is an ethanolic extract, and preferably, the extract is a dry extract, free of any traces of the solvent used to obtain it, for example, and preferably by vacuum evaporation of the solvent. It can also be done by azeotropic distillation, nebulization, freeze drying or zeodratation.
[0033] According to the invention, the term "physiologically acceptable medium" means, without limitation, an aqueous or hydro-alcoholic solution, an alcohol, a glycol or a hydroglycol, a water-in-oil emulsion, an oil-in-water emulsion, a microemulsion, a hydrogel, an anhydrous gel, a serum, a vesicular dispersion or a powder.
[0034] "Physiologically acceptable" means that the medium is suitable for topical or transdermal use, contacting mucous membranes, nails, scalp, hair, hair and skin of mammals (more particularly humans), and the composition can be ingested or injected into the skin without risk of toxicity, incompatibility, instability, allergic reaction, etc. This "physiologically acceptable medium" forms what is generally called an excipient for the composition.
[0035] The composition of the present invention can be applied to the face, body, neck, scalp, hair, eyelashes, body hair, nails, lips in any suitable form or vehicle known to those skilled in the art.
[0036] The composition according to the invention can be used in a carrierized form, in a bound form, incorporated or absorbed onto / onto macro-, micro- and nano-particles, in the form of capsules, spheres, liposomes, oleosomes, chylomicrons, sponges, microemulsions or nanoemulsions, or for example absorbed onto powdered organic polymers, talc, bentonite, spores or exines and other mineral or organic supports.
[0037] The compositions according to the invention may be provided in any galenic form and may also be delivered via a fabric support made of natural or synthetic fibers, wool, or any material suitable for contact with the skin, or may be used in clothing, such as day and night underwear, handkerchiefs or tissues, so as to allow the formation of a cosmetic or dermatological effect through this skin / fabric contact and allow topical delivery.
[0038] In particular and advantageously, according to the invention, the composition may comprise one or more additional active substances suitable for reinforcing the activity and / or acting in a complementary manner on one or more other activities. These additional active agents may be incorporated at the stage of the ingredients intended for the formulator or at the final stage of the composition forming the cosmetic product intended for the consumer.
[0039] In cosmetics, in particular, applications can be provided in skin care lines for face, body, hair and body hair as well as in the makeup-care range. These additional active substances can be of any category according to their function, application site (body, face, neck, chest, hands, hair, eyelashes, eyebrows, nails, lips, etc.), the end effect sought and the consumer target, for example, antioxidants, firming, moisturizing, nourishing, protecting, soothing, reshaping, filling (fat implants), for skin rejuvenation, freckle removal, concealer, anti-glycation, anti-aging, anti-wrinkle, weight loss, calming, muscle relaxation, anti-redness, stretch mark reduction, sun protection, etc.
[0040] Preferably, the Astragalus membranaceus extract according to the invention is mixed with active substances promoting the stimulation of molecules of the dermal extracellular matrix, such as collagen, elastin and / or hyaluronic acid.
[0041] Thus, it is of particular interest to combine the Huangqi extract according to the invention with one or more peptides selected from the peptides of the sequence KTTKS (SEQ ID NO 1), GHK, GQPR (SEQ ID NO 2) and / or KTFK (SEQ ID NO 3), or with an extract obtained by culturing plant cells of Leontopodium alpinum or Plantago lanceolata. According to the invention, the term "peptide of the sequence" includes peptides used in a derivatized form, especially at the N-terminal and / or C-terminal position, especially in an acylated form at the N-terminal position, such as in the form of an N-palmitoyl derivative, as well as complexes and salt forms with metal ions, especially acetates and chlorides.
[0042] Mention may be made of the following commercial ingredients, marketed by the Applicant, as active ingredients of particular interest for combination with the Fructus Astragali extract according to the invention: (including Pal-KTTKS (SEQ ID NO 4)), 3000 (comprising a mixture of Pal-GQPR (SEQ ID NO 5) and Pal-GHK), Crystalide TM (including Pal-KTFK (SEQ ID NO 6)), MAJESTEM TM (including Leontopodium alpinum cell extract) and / or SENESTEM TM (including Plantago asiatica cell extract).
[0043] Peptides of the sequence KTTKS (eg SEQ ID NO 1 or SEQ ID NO 4) or KTFK (eg SEQ ID NO 3 or SEQ ID NO 6) are preferred, since they are also advantageously active on the epidermis, which is complementary to the activity on the dermis.
[0044] The combination of the Chinese wolfberry extract according to the invention with an agent that stimulates elastin synthesis and improves the quality of elastic fibers is also particularly advantageous, especially for treating mature skin. TM The YR sequence peptide sold contains N-acetyl-Tyr-Arg-O-hexadecyl ester peptide, or VGVAPG (SEQ ID NO 7) sequence peptide, which is labeled as Dermaxyl TM It is sold under the trade name Pal-VGVAPG (SEQ ID NO 8) derivative.
[0045] The combination of the Astragalus membranaceus extract according to the invention with hyaluronic acid or with compounds which promote its synthesis is also particularly advantageous.
[0046] Furthermore, other active substances are conceivable, for example moisturizing active substances, which act on damage caused by radiation (especially UV, IR, blue light).
[0047] CTFA ("International Cosmetic Ingredient Dictionary & Handbook" (20th Edition, 2020)) published by "the Cosmetic, Toiletry, and Fragrance Association, Inc.", Washington, DC) records a wide variety of non-limiting cosmetic ingredients commonly used in the skin care and scalp care industries, which are suitable for use as additional ingredients in the compositions of the present invention.
[0048] Mention may be made of at least one compound chosen from vitamin B3, compounds such as niacinamide or tocopherol, retinoids such as retinol, hexamidine, tα-lipoic acid, resveratrol or DHEA.
[0049] Other additional skin care actives that are particularly useful can be found in the trade literature of Sederma and at www.croda.com.
[0050] The following commercially available active substances can also be used as examples: betaine, glycerol, l'Actimoist Bio2 TM (Activeorganics), AquaCactine TM (Mibelle AG Cosmetics), Aquaphyline TM (Silab), AquaregulK TM (Solabia), Carciline TM (Greentech), Codiavelane TM (Biotech Marine), Dermaflux TM (ArchChemicals, Inc), Hydra'Flow TM (Sochibo), Hydromoist L TM (Symrise), RenovHyal TM (Soliance), Seamoss TM (Biotech Marine), Argireline TM (Lipotec's trade name for acetyl hexapeptide-3), le spilanthol or known by the trade name Gatuline Expression TM Extract of Acmella oleracea, trade name Boswellin TM Boswellia serrata extract, Deepaline PVB TM (Seppic), Syn-AKE TM (Pentapharm), Ameliox TM , Bioxilift TM (Silab), PhytoCellTec TM Argan(Mibelle),Papilactyl D TM (Silab), Preventhelia TM (Lipotec), or one or more of the following active ingredients marketed by Sederma: Subliskin TM , Venuceane TM, Moist 24 TM , VegesomeMoist 24 TM , Essenskin TM , Juvinity TM , Revidrat TM , Resistem TM , Chronodyn TM , Kombuchka TM , Chromocare TM , Calmosensine TM , Glycokin factor S TM , Biobustyl TM , Idealift TM , Ceramide2 TM , Ceramide A2 TM , Ceramide HO3 TM , Legance TM , Intenslim TM , Prodizia TM , Beautifeye TM , Pacifeel TM , Zingerslim TM , Meiritage TM , Sebuless TM , Apiscalp TM , Rubistem TM , Citystem TM , Neonyca TM , NG Insaponifiables de Beurre de Karité TM , Majestem TM , Hydronesis TM , Poretect TM , Amberstem TM , Synchrolife TM , or a mixture thereof.
[0051] Among the plant extracts (in the form of classical plant extracts or prepared by in vitro processes) that can be used as additional active substances, mention may be made more particularly of extracts of the following plants: plants of the genus Hedera, for example, English Ivy (Hedera helix), Bupleurum chinensis, Bupleurum falcatum, Arnica Montana (Arnica Montana L), Rosemary (Rosmarinus officinalis N), Calendula officinalis, Sage (Salvia officinalis L), Ginseng (Panax ginseng), Ginkgo, St.-John's-Wort (Hyperycum perforatum), Ruscus aculeatus L, Filipendula ulmaria L, Orthosiphon stamincus Benth, artichoke (Cynara scolymus), algae (Fucus vesiculosus), birch (Betula alba), green tea, cola nut (Cola nipida), horse chestnut, bamboo, Centella asiatica, heather, rockweed, willow, mouse-ear, escine, atractylodes, golden chamomile (chrysanthellum indicum), Armeniacea, Atractylodis platicodon, Sinnomenum, Pharbitidis, Flemingia, Coleus (such as C. Forskohlii, C. blumei, C. esquirolii, C. scutellaroides, C. xanthantus and C.Barbatus, such as extracts of the root of Coleus barbatus, extracts of Ballote, Guioa, Davallia, Terminalia, Barringtonia, Trema, Antirobia, Cecropia, Argania, Dioscoreae such as Dioscorea opposita or Dioscorea zingiberensis, extracts of Ammi visnaga, Siegesbeckia, in particular Siegesbeckia orientalis, plant extracts of the Ericaceae family, in particular extracts of Vaccinium angustifollium or Arctostaphylos uva ursi, aloe vera, plants containing sterols (e.g., phytosterols), Manjistha (extracted from Rubia plants, especially Rubia cordifolia), and Guggal (extracted from Commiphora plants, especially Commiphora mukul), Kola nut extract, Chamomile, Red Clover extract, Pipermethysticum extract (Kava Kava from Sederma TM ), Bacopa monieri extract (Bacocalmine from Sederma TM) and sea whip extracts, extracts of Glycyrrhiza glabra, mulberry, Melaleuca (tea tree), Larrea divaricata, Rabdosia rubescens, Euglena gracilis, Fibraurea recisa Hirudinea, Chaparral Sorghum, sunflower extract, Enantia chlorantha, Mitracarpe of the genus Spermacocea, Buchu barosma, Lawsonia inermis L., Adiantium capillus-veneris L., Chelidonium majus, Luffa lindrica, "Japanese citrus" (Citrus reticulata blanco var.unshiu), Camelia sinensis, Imperata cylindrica, Glaucium flavum, Cupressus sempervirens, Polygonatum multiflorum, Lovely hemsleya, Sambucus nigra, Phaseolus lunatus, Centaurium, Macrocystis pyrifera, Turner grass, Anemarrhena asphodeloides, Portulaca pilosa, Humulus lupulus, Coffea Arabica, Ilex paraguariensis, Globularia cordifolia, Oxydendron arboretum, Albizzia julibrissin, Zingimber zerumbet smith, Astragalus membranaceus, Atractylodes macrocephalae, Plantago lanceolata, Leontopodium alpinum (or edelweiss), Mirabilis jalapa, Apium graveolens, Marrubium vulgare, Buddleja davidii Franch, Syringa vulgaris, or orchids.
[0052] The composition of the present invention may include other peptides besides the preferred peptides mentioned above, including, but not limited to, dipeptides, tripeptides, tetrapeptides, pentapeptides and hexapeptides and their derivatives. According to a specific embodiment, the concentration of the additional peptide in the composition ranges from 1×10 -7 % to 20%, preferably 1×10 -6 % to 10%, preferably 1×10 -5% to 5% by weight. The term "peptide" herein refers to peptides containing 10 amino acids or less, its derivatives, isomers, and complexes with other substances, such as metal ions (e.g., copper, zinc, manganese, magnesium, etc.). The term "peptide" refers to both natural peptides and (bio) synthetic peptides. It also refers to compositions containing peptides and which are found in nature and / or commercially available.
[0053] Suitable dipeptides for use herein include, but are not limited to, carnosine (βAH), YR, VW, NF, DF, KT, KC, CK, KP, KK, TT, PA, PM or PP.
[0054] Suitable tripeptides for use herein include, but are not limited to: RKR, HGG, GKH, GHK, GGH, GHG, KGH, KHG, KFK, KAvaK, KβAK, KAbuK, KAcaK, KPK, KMOK, KMO 2 K(MO 2 is dioxysulfoxide methionine), KVK, PPL, PPR, SPR, QPA, LPA, SPA, K(Ac)HG or K(Ac)GH (K(Ac) is acetylated lysine having an amine functional group on its side chain, disclosed in WO2017 / 216177), K(P)HG or K(P)GH (K(P) is lysine having proline grafted on its side chain), K(Pyr)HG or K(Pyr)GH (K(Pyr) is lysine having pyroglutamic acid grafted on its side chain), K(Hyp)HG or K(Hyp)GH (K(Hyp) is lysine having hydroxyproline grafted on its side chain, disclosed in WO2016 / 097965).
[0055] Suitable tetrapeptides for use as additional peptides herein include, but are not limited to, RSRK (SEQ ID NO 9), KTFK (SEQ ID NO 3), KTAK (SEQ ID NO 10), KAYK (SEQ ID NO 11) or KFYK (SEQ ID NO 12).
[0056] A suitable non-limiting example of a pentapeptide is KTTKS (SEQ ID NO 1), and suitable examples of a hexapeptide are GKTTKS (SEQ ID NO 13) and VGVAPG (SEQ ID NO 7).
[0057] Other suitable peptides for use according to the invention may be selected from the following list, but are not limited thereto: lipophilic derivatives of peptides, preferably palmitoyl (Pal) or myristoyl (Myr) derivatives, and the above metal complexes (e.g. copper complexes of the tripeptides HGG or GHK). Preferred dipeptides include, for example, N-palmitoyl-β-Ala-His, N-acetyl-Tyr-Arg-hexadecyl ester (Calmosensine from Sederma), TM , Idealift TM ), Pal-RT or Pal-KT (from Sederma). Preferred tripeptide derivatives include, for example, Pal-GKH and Pal-GHK (from Sederma), copper derivatives of HGG (Lamin from Sigma TM ), Lipospondin (N-Elaidoyl-KFK) and its conservatively substituted analogs, N-acetyl-RKR-NH 2 (peptide CK+), N-Biot-GHK (from Sederma), Pal-KAvaK, Pal-KβAlaK, Pal-KAbuK, Pal-KAcaK, or Pal-KMO 2 K (from Sederma ), Pal-KVK (DSM's Syn-Coll TM ), and their derivatives.
[0058] The present invention also mentions the anti-aging tripeptide of the general formula X-Pro*-Pro*-Xaa-Y described in WO2015181688, wherein Xaa is selected from Leu, Arg, Lys, Ala, Ser and Asp, and at the N-terminus, X is selected from H, -CO-R 1 and-SO 2 -R 1 , and at the C-terminal end, Y is selected from OH, OR 1 NH 2 、NHR 1 or NR 1 R 2 , R 1 and R 2 are independently selected from alkyl, aryl, aralkyl, alkaryl, alkoxy and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and / or sulphated, said groups may have heteroatoms, in particular O, S and / or N, in their backbone, and Pro* corresponds to proline, an analogue or a derivative thereof; including, for example, Myr-PPL-OH and Myr-PPR-OH.
[0059] The general formula X-(Xaa 1 )n-Pro*-Xaa 2 -Y pro-pigmentation and / or pro-mec dipeptides and tripeptides, wherein n=0, 1 or 2, Xaa 1 is a hydrophobic amino acid selected from Ala, Val, Met, Leu, Iso, Phe, Pro and their analogs and derivatives; or a polar amino acid selected from Ser, Thr, Tyr, Asp, Glu and their analogs and derivatives; and when n=2, the two amino acids Xaa 1 Can be the same or different; Xaa 2 is a hydrophobic amino acid selected from Ala, Val, Met, Leu, Iso, Phe, and analogs and derivatives thereof; is a basic amino acid selected from Arg, Lys, His, and analogs and derivatives thereof; at the N-terminus, X is selected from H, -CO-R 1 and-SO 2 -R 1 ; At the C-terminus, Y is selected from OH, OR 1 NH 2 、NHR 1 or NR 1 R 2 ; R 1 and R 2 are independently selected from alkyl, aryl, aralkyl, alkaryl, alkoxy and aryloxy groups, which may be linear, branched, cyclic, polycyclic, saturated, unsaturated, hydroxylated, carbonylated, phosphorylated and / or sulfided, with or without O, S and / or N heteroatoms in their backbone, and Pro* corresponds to proline, its analogs or derivatives; it includes, for example, the following peptides: Pal-SPR-OH, Pal-PPR-OH, Pal-QPA-OH, Pal-LPAOH, Myr-SPA-OH, Pal-PM-OH, Pal-PA-OH and Pal-PP-OH.
[0060] Suitable tetrapeptide derivatives for use as additional peptides according to the present invention include, but are not limited to: Pal-KTFK (SEQ ID NO 6) or Ela-KTFK (SEQ ID NO 14), Ela-KTAK (SEQ ID NO 15), Ela-KAYK (SEQ ID NO 16) or Ela-KFYK (SEQ ID NO 17). Suitable pentapeptide derivatives for use as additional peptides described herein include, but are not limited to: Pal-KTTKS (SEQ ID NO 4) (available from Sederma ), Pal-YGGFXaa (SEQ ID NO 18), wherein Xaa is Leu or Pro, or a mixture thereof.
[0061] Suitable hexapeptide derivatives for use herein include, but are not limited to: Pal-VGVAPG (SEQ ID NO 8), Pal-GKTTKS (SEQ ID NO 19), Pal-HLDIIXaa (wherein Xaa is Trp, Phe, Tyr, Tic, 7-hydroxy-Tic or Tpi) (SEQ ID NO 20) and derivatives thereof. Pal-GHK and Pal-GQPR (SEQ ID NO 5) ( 3000, Sederma).
[0062] The following commercially available peptides may also be mentioned as additional active ingredients:
[0063] -Vialox sold by Pentapharm TM (INCI name = Pentapeptide-3 (a synthetic peptide containing alanine, arginine, isoleucine, glycine and proline)), Syn-ake TM (β-Ala-Pro-Dab-NH-Bzl) or Syn-Coll TM (Pal-Lys-Val-Lys-OH);
[0064] -Argireline marketed by Lipotec TM (Ac-Glu-Glu-Met-Gln-Arg-Arg-NH 2 (INCI name = Acetyl Hexapeptide-3) (SEQ ID NO 21), Leuphasyl TM (Tyr-D-Ala-Gly-Phe-Leu) (SEQ ID NO 22), Aldenine TM (Gly-His-Lys), Trylagen TM (INCI name = Pseudoalteromonas ferment extract, hydrolyzed wheat protein, hydrolyzed soy protein, tripeptide-10 citrulline (reaction product of citrulline and tripeptide-10 (a synthetic peptide composed of aspartic acid, isoleucine and lysine)), tripeptide-1), Eyeseryl TM (Ac-β-Ala-His-Ser-His) (SEQ ID NO 23), Serilesine TM (Ser-Ile-Lys-Val-Ala-Val) (SEQ ID NO 24) or DecorinylTM (INCI name: Tripeptide-10 Citrulline = reaction product of citrulline and tripeptide-10 (a synthetic peptide composed of aspartic acid, isoleucine and lysine));
[0065] -Collaxyl sold by Vincience TM (Gly-Pro-Gln-Gly-Pro-Gln (SEQ ID NO 25)) or Quintescine TM (Cys-Gly);
[0066] -Cytokinol sold by Les Laboratoires Serobiologiques / Cognis TM LS (casein hydrolysate);
[0067] -Kollaren marketed by the Institute of Biotechnology Cellulaire TM (Gly-His-Lys), IP2000 TM (Pal-Val-Tyr-Val) or Meliprene TM (INCI name = Monofluorohexapeptide-1: reaction products of acetic acid and a synthetic peptide comprising arginine, glycine, glutamic acid, histidine, norleucine, p-fluorophenylalanine and tryptophan);
[0068] -Neutrazen sold by Innovations TM (Pal-His-D-Phe-Arg-NH 2 );or
[0069] -BONT-L-Peptide marketed by lnfinitecActivos TM (INCI name = Palmitoyl Hexapeptide-19: reaction product of palmitic acid and hexapeptide-19 (a synthetic peptide composed of asparagine, aspartic acid, lysine and methionine)), Timp-Peptide TM (INCI name = Acetyl Hexapeptide-20: reaction product obtained by acetylation of Hexapeptide-20 (a synthetic peptide composed of alanine, glycine, lysine, valine and proline)) or ECM Moduline TM (INCI name = Palmitoyl Tripeptide-28: reaction product of palmitic acid and tripeptide-28, a synthetic peptide composed of arginine, lysine and phenylalanine).
[0070] It is also possible to envisage combining the plant cells according to the invention with one or more cyclic peptides, especially those extracted from linseed oil and described in patent application FR1850845 in the name of the Applicant.
[0071] According to the present invention, there is also provided a method of improving the aesthetic appearance of the skin and its appendages comprising topically applying to the skin an effective amount of a cosmetic or dermatological composition according to the present invention, such as those described above.
[0072] "Topical treatment" or "topical application" means an application according to the invention which is intended to act at the site of its application, be it: the skin, mucous membranes and / or appendages.
[0073] The composition according to the invention may be applied topically to the targeted area.
[0074] An "effective" amount depends on various factors, such as the age of the person, the condition of the skin and appendages, the severity of one or more disorders or pathologies, the mode of administration, etc. An effective amount means a nontoxic amount sufficient to achieve the desired effect more or less significantly.
[0075] All percentages and ratios used herein are based on weight of the total composition and all measurements made are at 25°C unless otherwise specified.
[0076] For example, for cosmetic treatments on the face, the European Cosmetic Guidelines set a standard amount of 2.72 mg / cm2 for application of creams. 2 / day / person, the standard amount of body lotion is 0.5mg / cm 2 / day / person.
[0077] According to other specific characteristics, the cosmetic treatment method according to the invention can be combined with one or more other treatment methods targeting the skin, such as lumino-therapy, heat, vibration, electroporation, microneedle patches or aromatherapy treatments.
[0078] According to the present invention, a device or kit having several chambers can be recommended for applying the above-mentioned method, which may include (for example but not limitation): a first chamber containing a composition comprising the active ingredient of the present invention, and in a second chamber, excipients and / or another active ingredient and / or, in which case the compositions contained in the first and second chambers are considered to be a combined composition for simultaneous, separate or stepwise use in time, especially in one of the treatment methods mentioned above.
[0079] The compositions according to the invention are also suitable for therapeutic treatment of the skin in suitable dosages. Sequence Listing <110> SEDERMA <120> Cosmetic composition and treatment for treating sagging skin <130> COKI PCT <150> FR2002766 <151> 2020-03-20 <160> 25 <170> PatentIn version 3.5 <210> 1 <211> 5 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> 1 Lys Thr Thr Lys Ser 1 5 <210> 2 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> 2 Gly Gln Pro Arg 1 <210> 3 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Peptide compounds <400> 3 Lys Thr Phe Lys 1 <210> 4 <211> 5 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> N-terminal amidation of the palmitoyl chain <400> 4 Lys Thr Thr Lys Ser 1 5 <210> 5 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> N-terminal amidation of the palmitoyl chain <400> 5 Gly Gln Pro Arg 1 <210> 6 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> N-terminal amidation of the palmitoyl chain <400> 6 Lys Thr Phe Lys 1 <210> 7 <211> 6 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> 7 Val Gly Val Ala Pro Gly 1 5 <210> 8 <211> 6 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> N-terminal amidation of the palmitoyl chain <400> 8 Val Gly Val Ala Pro Gly 1 5 <210> 9 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> 9 Arg Ser Arg Lys 1 <210> 10 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> 10 Lys Thr Ala Lys 1 <210> 11 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> 11 Lys Ala Tyr Lys 1 <210> 12 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> 12 Lys Phe Tyr Lys 1 <210> 13 <211> 6 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> 13 Gly Lys Thr Thr Lys Ser 1 5 <210> 14 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> N-terminal amidation by Elaidoyl chain <400> 14 Lys Thr Phe Lys 1 <210> 15 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> N-terminal amidation by Elaidoyl chain <400> 15 Lys Thr Ala Lys 1 <210> 16 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> N-terminal amidation by Elaidoyl chain <400> 16 Lys Ala Tyr Lys 1 <210> 17 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> N-terminal amidation by Elaidoyl chain <400> 17 Lys Phe Tyr Lys 1 <210> 18 <211> 5 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> N-terminal amidation of the palmitoyl chain <220> <221> MISC_FEATURE <222> (5) <223> Xaa is proline P or leucine L <400> 18 Tyr Gly Gly Phe Xaa 1 5 <210> 19 <211> 6 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> N-terminal amidation of the palmitoyl chain <400> 19 Gly Lys Thr Thr Lys Ser 1 5 <210> 20 <211> 6 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> N-terminal amidation of the palmitoyl chain <220> <221> MISC_FEATURE <222> (6) <223> Xaa is Trp, Phe, Tyr, Tic, 7-hydroxy-Tic or Tpi <400> 20 His Leu Asp Ile Ile Xaa 1 5 <210> twenty one <211> 6 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <220> <221> MOD_RES <222> (1) <223> Acetylation at the N-terminus <400> twenty one Glu Glu Met Gln Arg Arg 1 5 <210> twenty two <211> 5 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> twenty two Tyr A La Gly Phe Leu 1 5 <210> twenty three <211> 4 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> twenty three Ala His Ser His 1 <210> twenty four <211> 6 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> twenty four Ser Ile Lys Val Ala Val 1 5 <210> 25 <211> 6 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptides <400> 25 Gly Pro Gln Gly Pro Gln 1 5 BRIEF DESCRIPTION OF THE DRAWINGS
[0080] The present invention will be better understood from the following detailed description of embodiments and in vitro and in vivo testing.
[0081] This detailed description is described with reference to the accompanying drawings, in which:
[0082] Figure 1 The improvement of skin sagging on the eyelid wrinkles on photographs of the same person before (left part of the figure) and after (right part of the figure) the cosmetic treatment according to the invention is illustrated;
[0083] Figure 2 The positioning of marionette lines at the corners of the mouth is shown;
[0084] Figure 3 The diagram shows the improvement of the elastic fiber network on a photograph of the same person under a microscope (after immunohistochemical labeling of elastin) before the cosmetic treatment according to the invention;
[0085] Figure 4 and Figure 3 Similarly, the results after 5 days of treatment are shown;
[0086] Figure 5Also illustrated is the improvement of skin sagging at the level of the eyelid wrinkles on an image captured by fringe projection of the same person before treatment according to the invention; and
[0087] Figure 6 and Figure 5 Similarly, the processed results are shown.
[0088] A / According to an example of a preferred cosmetic preparation according to the invention, a concentrated composition is formed which is intended for the manufacture of galenical preparations (see paragraph C / below)
[0089] Preparation Example of the Huangqi Leaf Extract According to the Invention: Crushed Huangqi Leaves are extracted in 15% ethanol reflux (15 g leaves in 100 mL). After cooling, the leaves are removed by coarse filtration. After cooling, the extract is filtered and then concentrated by vacuum evaporation of the ethanol. The dry residue constituting the dry extract is then formulated in a matrix, such as glycerol / water (approximately 80 / 20).
[0090] Active ingredients used in the cosmetic industry generally contain 0.1% to 20% by weight of dry extract relative to the total weight of the ingredient, preferably 1% to 5%.
[0091] This ingredient is usually formulated in a cosmetic preparation applicable on the skin at 0.1% to 20%, preferably 1% to 10%, more preferably 2% to 5% by weight of the ingredient relative to the total weight of the cosmetic preparation.
[0092] B / In vitro efficacy testing
[0093] The extract according to the invention was tested in aliquots at 0.5; 1; 2 or 3% of this extract at 1.11% by weight of dry extract (hereinafter referred to as "the extract according to the invention"). These doses correspond to the doses at which the extract according to the invention is recommended for use in the cosmetic treatment according to the invention. The aliquots were made of the dry extract diluted in a test excipient (e.g. culture medium).
[0094] 1 / Fibroblasts produce elastin
[0095] in principle
[0096] Human fibroblasts from the dermis of multiple elderly women approaching menopause were used.
[0097] Experimental protocol
[0098] When the cells reached confluence, the cells were contacted with the extract according to the invention in culture medium or not (for control examples), and then incubated at 37° C. and 5% CO 2Incubate for 5 days. After this contact, the cell layer is rinsed, fixed, and stained with anti-elastin antibody. Use fluorescent secondary antibody to develop the mark and take pictures under a microscope. These pictures are subjected to image analysis to quantify the production of elastin. Use the fluorescent dye HOESCHT 33258 of labeled DNA to counterstain the nucleus to evaluate the cell population, so the obtained fluorescence data is weighted.
[0099] result
[0100] Changes in elastin production by fibroblasts of donors approaching menopause. Effect of 0.5% of the extract according to the invention compared to the control (n=3):
[0101] Table 1
[0102] Age of donor 44 years old 47 years old 48 years old The extract according to the invention was compared with the control +63% +53% +94% Significance p<0.01 p<0.01 p<0.01
[0103] These results show that the extract according to the invention stimulates fibroblasts to produce elastin.
[0104] 2 / The quality of elastic fibers produced by fibroblasts
[0105] Experimental protocol
[0106] On the same cultures as above, after binarization of the photographs, the fiber quality can be assessed using an image analysis system, evaluating three parameters: the length of the fibers produced in the culture, the number of fibers produced and the complexity of the network formed, with the information weighted by subtracting the number of cells counterstained using the HOESCHT 33258 method from each parameter.
[0107] result
[0108] Changes in the quality of elastic fibers produced by fibroblasts from a 44-year-old donor: fiber length, fiber number and network complexity. Effect of 0.5% of the extract according to the invention compared to the control (n=3):
[0109] Table 2
[0110] Fiber length Number of fibers Network complexity The extract according to the invention was compared with the control x 12.5 x 14.5 x 16.7 Significance p<0.01 p<0.01 p<0.01
[0111] The image analysis system used showed that the fibers were longer (x 12.5), denser (x 14.5) and more connected (x 16.7) than the control due to the treatment according to the invention. Figure 3 and 4 can be clearly seen on the image.
[0112] 3 / Fibroblasts produce elastin MFAP4 and fibrillin 5 (which are proteins that mark elastic fibers)
[0113] in principle
[0114] This test complements the previous test and provides quantitative data on the production of three key proteins that build elastic fibers. This test is achieved by LC-MS / MS (liquid chromatography mass spectrometry).
[0115] Experimental protocol
[0116] 0.5% of the extract according to the invention was contacted with normal human fibroblasts (NHF) or not (control) for 7 days. After this contact, the cell layer was rinsed with a suitable buffer and the protein was added in quantity. Aliquots of these rinsed cells were recovered, all containing the same amount of protein, and were specifically cleaved using proteases to form peptide fragments of different sizes. First, the peptides were separated by liquid chromatography according to their hydrophobicity, then ionized, and then separated by sorting them in a detector according to their mass and their charge (m / z). Using software (Mascot TM ) to analyze the mass and charge of each element and to infer the presence and amount of pre-existing proteins. These data are then processed by bioinformatics / biostatistical analysis to identify biological processes and metabolic pathways regulated by the extracts according to the invention. The results are expressed as expression ratios between the treated examples and the control. Ratios greater than 1.5 are considered to be increased production of the target protein (relative to control + 50%). Variance studies and Student t tests are performed to determine the significance of the results.
[0117] result
[0118] Changes in three key proteins in elastic fiber formation. Quantification by LC-MS / MS. Effect of 0.5% of the extract according to the invention compared to the control (n=3):
[0119] Table 3
[0120] Elastin MFAP4 Fibrin 5 The extract according to the invention was compared with the control x 12.6 x 3.24 x 1.6 Significance p<0.01 p<0.01 p<0.01
[0121] These proteomic data confirm that the extract according to the invention is indeed able to stimulate the production of elastin and the two essential elements of mature elastic fibers.
[0122] 4 / Retention of dermal epidermal junctions (DEJs) and keratinocytes on skin explants
[0123] Experimental protocol
[0124] In order to confirm the effect of the extract according to the invention on two DJE components (collagen IV and laminin 5), a gel containing 3% of the extract or a placebo gel was applied once a day on the surface of skin explants of women approaching menopause. The skin was then selected and the synthesis of collagen IV and laminin 5 was visualized by immunohistochemistry (sections were labeled with primary antibodies specific for the proteins to be determined, and this labeling was visualized by fluorescent secondary antibodies specific for the primary antibodies). The intensity of this labeling was then quantified by image analysis of the photographs taken.
[0125] In addition, 0.5% of the extract according to the invention or its placebo (control) was applied to cultured human keratinocytes and collagen VII synthesis was measured by ELISA on the cell extracts after washing. The results were subtracted from the number of cells evaluated by counterstaining the nuclei with the fluorescent dye Hoescht 33258 that labels DNA.
[0126] result
[0127] Stimulation of collagen IV and laminin V synthesis on skin explants. Effect of 3% of the extract according to the invention (n=5):
[0128] Table 4
[0129] Collagen IV changes (%) Changes in laminin V (%) Placebo Reference Reference 3% of the extract according to the invention +27%;p<0.01 +17%;p<0.01
[0130] Changes in collagen VII synthesis measured by ELISA on cultured human keratinocytes. Effect of the extract according to the invention (n=3):
[0131] Table 5
[0132] Collagen VII changes (%) Comparison Reference 0.5% of the extract according to the invention +36%;p<0.01 3% of the extract according to the invention +148%;p<0.01
[0133] All these results show that the extract according to the invention has a direct potentiating effect on DJE by stimulating the synthesis of the three essential components of this JDE: collagen VII (+148%; p<0.01), shown on keratinocytes, collagen IV (+27%; p<0.01) and laminin V (+17%; p<0.01), shown on skin explants.
[0134] In the case of DJE disorders, the extract according to the invention can therefore improve the aging of the skin by combating the loss of flexibility and elasticity.
[0135] 5 / Contractility and cell resilience
[0136] in principle
[0137] The contractile function of fibroblasts is important for ensuring good elasticity of the skin. Applying a glycated substance (MGO: methylglyoxal) to fibroblasts is able to mimic the loss of contractility of fibroblasts that occurs during accelerated aging.
[0138] Experimental protocol
[0139] Fibroblasts were contacted with non-toxic amounts of MGO for 2 days in the presence or absence of extracts according to the invention. After this contact, the cells were contained in a collagen gel to form a dermis equivalent known as a lattice. Fibroblasts anchored themselves to the collagen and began to contact the gel as they would in the skin. After 16 h, contraction was measured using an ImageQuant LAS4000 imager to track changes on the gel surface.
[0140] result
[0141] Changes in contraction of fibroblasts subjected to stress. Effect of 0.5% of the extract according to the invention (n=3):
[0142] Table 6
[0143] Gel surface Gel shrinkage at 16h (%) Reduction in shrinkage variation (%) Control without MGO 100% Reference MGO 59.9% 40.1;p<0.01 MGO + 0.5% extract according to the invention 93.8% -6.2%; nsd
[0144] NSD: No significant difference
[0145] These results show that non-cytotoxic amounts of MGO strongly delayed the contraction in the control (-40% compared to the unstressed control) and that the presence of 0.5% of the extract according to the invention avoided this delay of contraction and restored contraction values not significantly different from the unstressed control.
[0146] C / Galen / Formulation Examples of Compositions According to the Invention
[0147] The composition is a cosmetic cream containing the active ingredients described in section A / above, and 1.11% by weight of dried Astragalus membranaceus extract.
[0148] Table 7
[0149]
[0150]
[0151] It is preferred to add to this composition Stimulates components of extracellular matrix (especially collagen) molecules such as:
[0152] - and / or
[0153] - As mentioned above, it is sold by Sederma.
[0154] Optionally, other ingredients may be added, such as:
[0155] Soothing ingredients for sensitive skin, such as PACIFEEL TM , sold by Sederma, comprises an extract of Mirabilis Jalapa.
[0156] Moisturizing ingredients such as:
[0157] -AQUALANCE TM , marketed by Sederma, is an osmotic protective moisturizing active ingredient composed of lobster myosine and erythritol.
[0158] -REVIDRATE TM , marketed by Sederma, improves in particular the adhesion of the epidermis and its hydration.
[0159] Ingredients that promote a more radiant complexion, such as EVERMAT TM , sold by Sederma, contains a combination of Enantia chlorantha extract rich in protoberberines and oleanolic acid; reduces pore size and brightness; and refines the texture of acne-prone skin.
[0160] Moisturizing / soothing ingredients, such as OPTIM HYAL TM , marketed by Sederma, contains acetylated glucuronic acid oligosaccharides having a structure similar to that of hyaluronic acid fragments.
[0161] Sebum regulating ingredients such as:
[0162] -SEBULESS TM , marketed by Sederma, contains an extract of Syringa vulgaris obtained by in vitro cell culture, it is a sebum regulator, purifies, controls oil and refreshes the complexion, and conceals blemishes.
[0163] -PORETECT TM , sold by Sederma, contains a combination of flaxseed and celery extracts titrated with cylolinopeptide and senkyunolides, which provide firmness, tone and density to the skin, thereby strengthening the pore-retention structure that collapses with aging.
[0164] Ingredients that act on the elastic properties of the skin / skin barrier such as:
[0165] -IDEALIFTTM , marketed by Sederma, contains N-acetyl-tyrosyl-arginyl-O-hexadecyl ester lipid dipeptide, which counteracts sagging of the face and improves resistance to gravitational forces, in particular by stimulating elastin.
[0166] -DERMAXYL TM , sold by Sederma, combines ceramide 2, a binder of the stratum corneum, and pal-val-gly-val-ala-pro-gly, a palmitoylated matrikine, which smooths wrinkles and repairs the skin barrier.
[0167] Anti-fatigue ingredients such as PRODIZIA TM , marketed by Sederma, includes Albizia julibrissin extract, which promotes a visible reduction in the signs of fatigue: dark circles, eye bags, dull complexion and a haggard look by repairing and protecting the skin from damage caused by glycation.
[0168] Anti-pollution ingredients such as CITYSTEM TM , marketed by Sederma, is based on plant cells obtained in vitro from hollyhocks with a high concentration of forsythiaside B; used to fight pollution attacks: softens and smoothes the skin, refines the skin texture, reduces the visibility of blackheads, makes the skin bright and pure.
[0169] D / In vivo studies
[0170] in principle
[0171] The efficacy of the cosmetic treatment of the invention was evaluated on a total of 90 female volunteers during two complementary studies: one was a Caucasian group and the other was Chinese volunteers. All of them had obvious signs of aging on their faces: sagging skin, loss of harmony of face, depressions and contours, loss of skin elasticity in this area. All volunteers were close to the average age of menopause or several years after menopause. The studies conducted used metrological methods (measurement), expert analysis (judgment) and self-assessment (perceived effect).
[0172] These two studies were performed independently of each other and allowed the evaluation of facial sagging, loss of viscoelastic properties, and changes in wrinkles and relief.
[0173] They were conducted over a two-month period and compared with a placebo cream consisting of:
[0174] Facial coordination
[0175] -Measure facial contours using a fringe projection device
[0176] -Measurement of facial dewlap using fringe projection device
[0177] - Expert evaluation of dewlap from photos
[0178] Viscoelastic properties of the face:
[0179] -Using ElastiMeter TM Measure the elasticity of the dewlap.
[0180] -Use Cutometer TM Measuring facial skin elasticity,
[0181] -Use Cutometer TM Measuring facial skin elasticity / recovery after stress.
[0182] Eyelid appearance:
[0183] -Measurement of eyelid wrinkle height using a fringe projection device,
[0184] -Measure the volume of this wrinkle using a fringe projection device,
[0185] -Measure wrinkle area using a fringe projection device,
[0186] - Expert evaluation of the appearance of eyelid drooping from photographs,
[0187] - The tired appearance of the eyes was perceived by the volunteers.
[0188] Marionette lines around the mouth:
[0189] -Measure the depth of marionette lines by fringe projection
[0190] - Photos of perioral sagging evaluated by experts
[0191] - Roughness was evaluated visually and tactilely by experts
[0192] Experimental protocol
[0193] The study was conducted in France on Caucasian volunteers, with a maximum of 38 female volunteers, with a mean age of 57 years (49-66 years). Regarding the distribution of volunteers according to years since menopause, 60% were 0-5 years since menopause (including 34% 0-2 years), and 40% were 6-10 years since menopause (including 32% 6-8 years).
[0194] The study was conducted in Chinese volunteers in China (Guangzhou), with a maximum of 52 women, with a mean age of 56 years (range 51-60 years), and confirmed menopause for less than 7 years.
[0195] Study type, duration and application
[0196] The volunteers were unaware of the type of product (active or placebo) they were applying on their face for 8 weeks.
[0197] The group of 38 women was divided into two groups as follows:
[0198] - 20 women applied the cream according to the invention (cream described in Table 7) morning and evening
[0199] - 18 women applied a placebo cream (same formula but without the active ingredient according to the invention) morning and evening
[0200] Before and after application, different measurements and groups were obtained on several devices according to Table 8 below.
[0201] Table 8
[0202] T0-----------------------------------------> T8 Week Stripe projection (outline, dewlap, eyelids) Stripe projection (outline, dewlap, eyelids) <![CDATA[Elastimeter TM )]]> <![CDATA[Elastimeter TM )]]> Photos (expert judgment, self-assessment) Photos (expert judgment, self-assessment)
[0203] The group of 52 Chinese women was divided into two groups as follows:
[0204] - 26 women applied the cream according to the invention (cream described in Table 7) morning and evening
[0205] - 26 women applied a placebo cream (same formula, but without the active ingredient according to the invention) morning and evening.
[0206] According to Table 9 below, different measurements were performed before and after application.
[0207] Table 9
[0208] T0----------------------------> T4 week----------> T8 Week Stripe projection (puppet pattern) Fringe Projection <![CDATA[Elasticity, resilience (Cutometer TM )]]> Elasticity, resilience Clinical evaluation (roughness) Clinical evaluation Clinical evaluation photo photo photo
[0209] statistics
[0210] Statistical studies were performed using the relevant Student t test, the nonparametric Wilcoxon test or the Mann-Whitney test. For comparison of the effects with T0, two-sided tests were performed on paired series. For comparison of the products with each other, two-sided tests were performed on unpaired series. For questionnaire evaluation, the Khi-2 test was used.
[0211] Methods and Results
[0212] 1. Evaluation of sagging facial features: contour / dewlap
[0213] For the measurement of the facial contour (facial oval), the volunteers were positioned on a fringe projection table and stereo measurements were combined to ensure that the volunteers were positioned exactly in the same way a few weeks later. Characteristic shadows (fringe lines) were projected onto the face and their deformation caused by the skin indentations was measured by triangulation. This technique allowed the three-dimensional reconstruction of the indentations. The length of the developed contour was measured using the same anatomical landmarks between the two times.
[0214] For dewlap, the volume of the skin area on the mandible where dewlap occurs was measured at exactly the same location at two time points.
[0215] 1.1. Fringe projection: Effect of the treatment according to the invention on changes in sagging facial contours and dewlap
[0216] Table 10
[0217]
[0218] nsd: no significant difference compared with T0
[0219] These results show a significant improvement in facial contour in volunteers treated according to the invention compared to placebo (-5.1%; p<0.05).
[0220] In addition, there was a significant improvement in the dewlap, whose volume was significantly reduced after the treatment according to the invention compared to T0 (-8.2%, p<0.06), but not in the volunteers using the placebo (nsd). The difference between the two groups clearly supported the treatment according to the invention, since a total reduction of -11.4% was observed, which was significant relative to the placebo (p<0.05). The face was thus tightened and more toned.
[0221] 1.2. Expert evaluation of standardized photographs of dewlap
[0222] Standardized photographs were taken at T0 and T8 weeks using a photo bench equipped with a high-definition digital camera, dedicated lighting, and a system to position the volunteers identically at different time points. Six experts reviewed the photographs and judged dewlap improvement (reduction in facial skin sagging).
[0223] The results show that in the volunteers treated according to the invention, the dewlap was significantly improved, with less sagging in 34% of cases compared to T0. The experts noted that in the volunteers using the placebo, an improvement was perceived only in 14% of the volunteers. The invention / placebo difference was significant (p<0.05) in favor of the treatment according to the invention.
[0224] 1.3. Evaluation of biomechanical properties of facial skin
[0225] Using ElastiMeter TM (It can measure skin elasticity in a highly reproducible way) The elasticity of the skin of the dewlap is measured on a Caucasian panel. This measuring tool uses a probe equipped with a piston which applies a constant deformation to the skin using a metal rod. The resistance of the skin to this deformation is recorded. The device has a tracking system which identifies contact with the skin.
[0226] use MPA580 measures the elasticity and resilience of cheek skin during deformation in Chinese volunteers. The device is directly derived from It draws the skin into a small tube. It is widely used to evaluate the effect of cosmetic products. It has been used to show the correlation between changes in the biomechanical properties of the skin and the age of volunteers, especially the face (MONDON et al., 2010). The parameters studied were the Ur / Ue and Ur / Uf ratios, both of which are closely related to skin elasticity. These parameters are recommended when evaluating the anti-aging effect of cosmetic products (KRUEGER et al., 2011).
[0227] 1.3.1 Obtained Elastimeter TM Results: Changes in skin elasticity of dewlap; N = 35; 5 measurements / site:
[0228] Table 11
[0229]
[0230]
[0231] These results show that the elastic properties of the skin of the volunteers who applied the cream according to the invention improved by 8.18%. This is significant (p<0.05) compared to the placebo cream which did not produce any change (-0.17, nsd vs T0).
[0232] 1.3.2. Obtained Cutometer TM Results: Changes in elasticity parameters of dewlap skin; N = 51 volunteers, n = 3 measurements / site:
[0233] Table 12
[0234]
[0235] These results obtained with Chinese volunteers fully confirm those obtained with Caucasian volunteers. The results show that, on the face of postmenopausal women, the use of the cream according to the invention very advantageously improves the age-related elasticity parameters studied. Compared with the placebo, the elasticity is 14% (p<0.05), for the skin recovery is 10.7% better (p<0.05).
[0236] 2. Eyelid evaluation (wrinkles, sagging appearance, fatigue)
[0237] 2.1. Evaluation of eyelid wrinkles
[0238] According to the experimental protocol using fringe projection ( Figure 5 and 6Wrinkles were studied on Caucasian volunteers (as shown in Figure 1). Three parameters of eye bags were extracted from the eyelids: maximum height, volume and occupied area.
[0239] Results: Changes in upper eyelid wrinkles, eyelid wrinkle height and volume; N = 29
[0240] Table 13
[0241]
[0242] Results: Upper eyelid wrinkles, changes in occupied surface; N = 29:
[0243] Table 14
[0244]
[0245] These results show that the treatment according to the invention makes it possible to very significantly reduce the wrinkles of the upper eyelid after two months of use. In parallel, there is a tendency with the placebo to reduce one of the parameters (volume), although not significantly.
[0246] Compared to the placebo, the maximum height was significantly reduced by 24.7% (p<0.05). The volume of this wrinkle was greatly reduced according to the invention (-32%, p<0.05 vs placebo). In addition, it must be noted that the projected surface area of this small wrinkle was significantly reduced by 30% (p<0.01) compared to the placebo case.
[0247] 2.2. Expert evaluation of ptosis eyelid parameters
[0248] Using the technique described in paragraph 1.2, 6 experts examined the photographs and judged the appearance of eyelid droop in the Caucasian panel.
[0249] The results showed that for the volunteers who used the cream according to the invention there was a significant improvement, ie in 51% of cases the eyelids showed less drooping compared to T0. The experts noted that only 31% of the 15 volunteers who used the placebo perceived an improvement.
[0250] The 20% difference was significant (p<0.05) supporting the present invention ( Figure 1 As shown in Figure 1 The eyelids are clearly tightened and wrinkles are less visible).
[0251] 2.3. Volunteers’ evaluation of eye fatigue parameters
[0252] After using the cream according to the invention for two months, 38 Caucasian volunteers judged in front of a mirror whether their eyes looked more or less tired.
[0253] The results show that for the 20 volunteers who used the cream according to the invention, there was a significant improvement, i.e. the eyes looked less tired in 80% of cases compared to T0. For the 18 volunteers who used the placebo, an improvement was perceived only in 39% of cases. The difference of 41% is very clear in favor of the invention (p<0.01 vs. placebo).
[0254] 3. Evaluation of marionette lines (mouths) and depressions
[0255] These parameters were evaluated on Chinese volunteers. They were placed in a fringe projection system combined with a stereo measurement tool (see above for details). Photos of the volunteers were also taken.
[0256] 3.1 Depth of marionette lines after 1 month ( Figure 2 )
[0257] Results: Changes in depth of marionette lines after 1 month; N = 52:
[0258] Table 15
[0259]
[0260]
[0261] The results show that for the volunteers who used the cream according to the invention, there was a 6.9% reduction trend in the depth of the marionette lines relative to T0, while for the volunteers who used the placebo, a significant deepening of the wrinkles of 7.9% was observed after this same one-month period. However, the comparison of the two cases supports the invention, since the difference of 14.8% is significant (p<0.05 vs. placebo).
[0262] 3.2. Skin Dimpling
[0263] 3.2.3 Skin depression around crow's feet at the corners of the eyes
[0264] This parameter was evaluated on Caucasian volunteers. The roughness parameter of crow's feet wrinkles at the corners of the eyes was monitored. 50 consecutive curves were created for each case.
[0265] Results: Changes in eye corner roughness; N = 30
[0266] Table 16
[0267]
[0268] The results show that after 8 weeks of application of the cream according to the invention, the dimpling of the skin improves. In fact, there is a total reduction of 20% in roughness. The placebo also has a milder effect. However, the difference between the product and the placebo is significant in favor of the invention (-9.5%; p<0.05).
[0269] 3.3. Evaluation of roughness after 1 month
[0270] This parameter was evaluated on Chinese volunteers. In addition to the metrological aspects seen above (showing a clear improvement in canthus roughness), the volunteers' skin roughness was evaluated visually and tactilely by experts at T0 and at 1 month using a 10-point rating scale ranging from soft (0) to stiff (9).
[0271] Results: Changes in facial skin roughness of volunteers after 1 month; N = 52:
[0272] Table 17
[0273]
[0274] These results show that the experts clearly observed an improvement in facial roughness in the volunteers who applied the cream according to the invention (-5.6% vs. T0, p<0.01). Compared to the volunteers who applied the placebo, the difference was significant in favor of the invention (-4.6% vs. placebo; p<0.05).
Claims
1. Use of a cosmetic composition comprising an ethanol extract of the leaves of Engelhardtia chrysolepsis Hance for the non-therapeutic cosmetic treatment of skin sagging, said treatment being suitable for increasing elastin synthesis in the extracellular matrix and for improving the number of elastic fibers and the quality of their network.
2. Use according to claim 1, wherein the treatment is suitable for increasing skin elasticity.
3. Use according to claim 1, wherein the treatment is suitable for increasing skin elasticity.
4. The use according to claim 1, wherein the treatment is suitable for smoothing skin depressions.
5. Use according to claim 1, wherein the treatment is suitable for reducing dewlap and ptosis of the eyelids, and the corresponding skin wrinkles.
6. The use according to claim 1, wherein the treatment is suitable for premenopausal or menopausal female skin.
7. Use according to claim 1, wherein the treatment is a repair treatment.
8. The use according to any one of claims 1 to 7, wherein the extract is combined with an active substance that promotes the synthesis of extracellular matrix molecules.
9. The use according to claim 8, wherein the active substance is selected from: one or more peptides of the sequences KTTKS, GHK, GQPR, KTFK, VGVAPG, YR, or an extract obtained by culturing plant cells of Leontopodium alpinum or Plantago lanceolata.
10. The use according to claim 9, characterized in that The active substance is Pal-KTTKS.
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