WO2020165365A1

WO2020165365A1 - Active ingredient for homogenizing complexion, in particular skins with an olive carnation

Info

Publication number: WO2020165365A1
Application number: PCT/EP2020/053800
Authority: WO
Inventors: Caroline RINGENBACH; Nathalie ROUYER; Olga GRACIOSO
Original assignee: Sederma
Priority date: 2019-02-14
Filing date: 2020-02-13
Publication date: 2020-08-20
Also published as: FR3092759B1; FR3092759A1; EP3923904A1

Abstract

The invention provides the use of undifferentiated or dedifferentiated plant cells, whole and/or lysed, from Buddleja davidii Franch. obtained by an in vitro cell culture process, and/or an intracellular extract of said cells free of cellular debris, for a topical non-therapeutic cosmetic treatment to homogenize the complexion of the skin, in particular via prevention and/or treatment of pigment and/or skin texture heterogeneities. The treatment is particularly suitable for the treatment of skins of phototype III to V developing spots and areas of hyperpigmentation, and furthermore especially for the treatment of skin with olive carnation.

Description

ACTIVE INGREDIENT FOR HOMOGENIZING COMPLEXION,

IN PARTICULAR SKINS WITH AN OLIVE CARNATION

TECHNICAL FIELD

The present invention relates to a cosmetic active ingredient for homogenizing skin complexion, a cosmetic composition comprising said ingredient and uses thereof in cosmetics on the skin and appendages of mammals, humans or animals. The cosmetic, dermatological, hygiene and personal care industries are aimed.

BACKGROUND ART

A homogeneous and radiant complexion is synonymous of freshness and youth. It is one of the main objectives of cosmetic products, along with combating dryness and wrinkles.

Skin pigmentation and the appearance of spots can be limited by avoiding sun exposure or by fdtering solar radiation. It is also possible to use depigmenting treatments. However, these treatments, often acidic, laser types or based on hydroquinone or mercury salts, tend to irritate the skin locally. On naturally pigmented dark skin, such as skin of phototype III to V (depending on the scale by Fitzpatrick), they favor, by rebound effect, the overpigmentation of the skin. This problem affects women from different parts of the world, in the Mediterranean, Southern Europe, Latin America, the Middle East and Central Asia. For these women, this will result in unsightly spots or overpigmented areas, for example around the mouth, which will take a long time to fade naturally. Another problem encountered with the skins of these phototypes III to V, is linked to their complexion: golden in summer, and olive or grayish in winter (with a warm and neutral undertone) and therefore much less aesthetic in winter.

To overcome these two unsightly effects, spots and hyperpigmented areas, and olive and/or dull complexion, women most often use makeup.

SUMMARY OF THE INVENTION

The aim of the present invention is to provide a cosmetic or dermatological treatment to homogenize the complexion, and furthermore a treatment particularly effective for treating dark skin, of phototype III to V, to restore their radiance, in particular giving to this type of skin an amber colour. The aim is also to provide an active ingredient for this purpose.

To this end, the present invention provides the use of undifferentiated or dedifferentiated plant cells, whole and/or lysed, from Buddleja davidii Franch. obtained by an in vitro cell culture process, and/or an intracellular extract of said cells free of cellular debris, for a topical non-therapeutic cosmetic treatment to homogenize the complexion of the skin. Preferably according to the invention, the cells are used in the form of a mixture of whole and lysed cells suspended in a physiologically acceptable medium, preferably a hydrophilic matrix. Preferably, the mixture comprises at least 10% of whole cells, more preferably between 30% and 70%, typically between 40 and 60%, in general approximately 50% of whole cells.

The present invention provides also the use of undifferentiated or dedifferentiated plant cells, whole and/or lysed from Buddleja davidii Franch. obtained by an in vitro cell culture process, and/or an intracellular extract of said cells free of cellular debris, for the manufacture of an active cosmetic ingredient for homogenizing the complexion of the skin and of a topical cosmetic composition comprising said active ingredient.

In the following description, the terms "plant cells of Buddleja davidii Franch." when not otherwise specified, include undifferentiated or dedifferentiated, whole and/or lysed plant cells, from Buddleja davidii Franch. obtained by an in vitro cell culture process, and/or an intracellular extract of said cells free of cellular debris.

According to another aspect, the present invention provides a composition comprising the active ingredient according to the invention based on plant cells of Buddleja davidii Franch., as defined above, such a composition being able to be used in cosmetics or for a medical dermatological application for the care of skin, its appendages and mucous membranes.

According to yet another aspect, the present invention also provides a method for homogenizing the complexion of the skin comprising the topical application to the skin of an effective amount of a cosmetic composition comprising the active cosmetic ingredient according to the invention, such as described and defined above.

The Buddleja davidii Franch. or Buddleia davidii Franch. (commonly called“Butterfly Bush” and“Mi Meng Hua” in Chinese), is a shrub with frail but abundant branches that is adorned in summer with fragrant flowers of various colours depending on the plants. Native to China, Buddleja davidii Franch., is widely used in ornamental gardens around the world where it attracts pollinator butterflies. It very easily colonizes dry and fallow land in Europe, New Zealand, the United States and Australia.

The Buddleja davidii Franch. is traditionaly used in China to drain fire from the body and calm red, painful, weeping, light-sensitive and swollen eyes. In Korea, it is used in the same way, but also for intestinal inflammatory conditions and to reduce the sensitivity of the skin.

Plant cells from Buddleja davidii Franch. according to the invention are rich in protective phytomolecules for skin cells including the verbascoside (also called acteoside or kusagenin).

As shown by the in vitro and in vivo tests detailed below, the treatment according to the invention acts on two causes responsible for a non-homogeneous complexion: - heterogeneities of pigmentation; and

- heterogeneities of texture (of relief), which do not return the light homogeneously.

On the pigmentation heterogeneities, it has been shown that the active agent according to the invention has a lightening effect on dark spots and areas (hyperpigmented), in particular thanks to an action on the melanin production which gives its colour to the skin, but also thanks to an action on the melanin distribution in the epidermis.

On the texture heterogeneities, it has been shown that the active agent according to the invention has a smoothing effect.

The present invention thus provides a treatment suitable for preventing and/or treating pigmentary and/or texture heterogeneities of skin.

The treatment according to the invention is also particularly suitable for skins of phototype III to V, with a complexion rendering that is more homogeneous and radiant, in particular adapted to skins of phototype IV (see the in-vivo tests detailed below).

More particularly, the lightening effect of the ingredient according to the invention has been shown through various in vitro tests.

The most classic in vitro tests showing a lightening effect are those carried out on melanocyte cultures. These skin cells produce melanin, which is responsible for the dark pigmentation of the skin, and a good cosmetic lightener lowers the melanin production. One way of achievement is to decrease the activity of tyrosinase, the first enzyme in the melanin biosynthesis chain, which converts tyrosine to DOPA-quinone. Another way is to decrease the activity of the enzyme involved in the continuation of this biosynthesis, the dopachrome tautomerase (DCT). The three parameters (melanin, tyrosinase and DCT) were tested on melanocyte cultures.

Another way to limit pigmentation and lighten the skin is to slow down the transfer of melanosomes (globules containing melanin) which takes place by phagocytosis of the melanocyte toward neighboring keratinocytes. This effect was shown in an in vitro test consisting in applying artificial melanosomes (fluorescent beads) in contact with keratinocytes and evaluating phagocytosis by measuring fluorescence.

Furthermore, it has been shown that the ingredient according to the invention contributes to the reinforcement of the dermo-epidermal junction (DEJ) via the stimulation in keratinocyte cultures of the production of collagen VII and laminins, which are important constituents involved in the good anchoring of keratinocytes and melanocytes in the DEJ. This good anchoring will make the melanocytes less receptive to propigmenting stimuli, these stimuli which are responsible for the deregulation of their activities and which lead them to overproduce melanin. There is also a link between the quality of the skin barrier and the pigmentation of the skin. A reinforced skin barrier helps to slow down the penetration of allergens and irritants which can lead to overpigmentation. Likewise, melasma (hyperpigmentation in the face) is associated with an impaired barrier function. Finally, in age spots type disorders, affecting almost all people over fifty, the reduction of the gene for involucrine, a major actor in the skin barrier, is observed. The ingredient according to the invention shows this effect by the production of two markers of the skin barrier (involucrine and cytokeratin-I) on keratinocytes.

Furthermore, the ingredient according to the invention has shown its ability to stimulate the production of hyaluronic acid on keratinocyte cultures. Hyaluronic acid is a major constituent of the epidermis participating in the barrier function (see above) as well as in maintaining satisfactory hydration of the skin. It is in the form of an aqueous and nourishing gel which fills the spaces between the keratinocytes. In this way, it prevents dryness of the skin, which is known to alter the texture of the skin, giving it a rough feel.

According to another aspect, it is known that with age and sun exposure, the proteins of the skin accumulate AGEs (“Advanced Glycation End-products” or EPGs, end-products of Glycation), a phenomenon amplified by a food too rich in sugars. AGEs are indeed byproducts of the binding of amino acids with sugars. In the skin, fibronectin, laminins and collagens, for example, accumulate these AGEs, making them less functional. It has also been shown that AGEs cause denaturation of the quality of hyaluronic acid. It is also known that the different types of AGEs cause on isolated melanocytes and in human skin explants a stimulation of melanogenesis and an increase in the activity of tyrosinase. These inductions remain moderate but are constant, unlike exposure to UVs. They could be the beginning of an explanation for the appearance of age spots on sites not exposed to the sun.

Finally, AGEs have a negative impact on the complexion. In people with diabetes, a large amount of AGEs contributes greatly to making the skin appear older, duller and more stained.

Therefore, AGEs have a major deleterious role in the skin. Inhibiting their formation is therefore an important property for an active cosmetic ingredient in order to limit pigmentation and keep a radiant complexion. This property has been demonstrated for the active ingredient according to the invention.

The treatment according to the invention is thus particularly suitable for lightening the skin, countering the glycation of proteins, smoothing the skin, stimulating the production of hyaluronic acid, strengthening the skin barrier and/or strengthening the dermo-epidermal junction.

The tests showing the efficacy of the ingredient according to the invention are further detailed in the following description. In a usual manner, the plant cells of Buddleja davidii Franch. according to the invention can be combined with other active agents, at effective concentrations which can act synergistically or for enhancing its activity, such as the following usual agents: anti-aging, anti-wrinkle and fine lines, lightening, moisturizing, humectants, astringants, anti-seborrhea, slimming, anti-acne, anti inflammatory, antioxidants, acting on the radiance of the complexion, the signs of skin fatigue, redness, dark circles and bags under the eyes, smoothing, soothing easily irritable skin, anti-glycation, volumizing, restructuring, anti-carbonylation, dermo-relaxing, protective against pollution and different radiations (UV, IR, blue light, etc.), anti-regrowth hair, acting on the stratum corneum, on the dermo-epidermal junction, on the production of HSP proteins, on firmness, elasticity, skin tone, hair regrowth (eyelashes, eyebrows for example), etc.

Plant cells from Buddleja davidii Franch. according to the invention can also be combined with at least one of the compounds chosen from vitamin B3 compounds, compounds such as niacinamide or tocopherol, retinoid compounds such as retinol, hexamidine, a-lipoic acid, resveratrol or DHEA, hyaluronic acid, peptides, in particular N-acetyl-Tyr-Arg-O-hexadecyl ester, Pal-VGVAPG (SEQ ID NO: 1), Pal-KTTKS (SEQ ID NO : 2), Pal-GHK, Pal-KM02K, Pal-GQPR (SEQ ID NO: 3), Pal-KTFK (SEQ ID NO : 4) and Pal-K(P)HG, which are known active ingredients used in topical cosmetic or dermo-pharmaceutical compositions.

"Physiologically acceptable medium" means according to the present invention, without limitation, an aqueous or aqueous-alcoholic solution, a water-in-oil emulsion, an oil-in-water emulsion, a microemulsion, an aqueous gel, an anhydrous gel, a serum, a dispersion of vesicles, a powder, or a heterogeneous liquid/particle medium.

"Physiologically acceptable" means that the compositions are suitable for topical or transdermal use in contact with mucous membranes, nails, scalp, hair, body hair and skin of mammals and more particularly of human, without risk of toxicity, incompatibility, instability, allergic response, among others. This "physiologically acceptable medium" forms what is usually called the excipient of the composition.

According to the present invention, there is therefore provided the use of undifferentiated or dedifferentiated plant cells, whole and/or lysed, of Buddleja davidii Franch. obtained by an in vitro cell culture process, and/or an intracellular extract of said cells free of cellular debris, for preparing a cosmetic composition for a topical non-therapeutic cosmetic treatment to homogenize skin complexion.

A composition according to the invention can be applied to the face, the body, the neckline, the scalp, the hair, the eyelashes, the body hairs, in any form or vehicle known to those skilled in the art, in particular in the form of a solution, dispersion, emulsion, paste or powder, individually or as a premix or be conveyed individually or as a premix by vectors such as macrocapsules, microcapsules or nanocapsules, macrospheres, microspheres, or nanospheres, liposomes, oleosomes or chylomicrons, macroparticles, microparticles or nanoparticles, macro-sponges, micro-sponges or nano-sponges, microemulsions or nanoemulsions, or adsorbed on powdery organic polymers, talcs, bentonites, spores or exines and other mineral or organic supports.

In cosmetics, applications can be proposed in particular in the ranges of skin care for the face, body, hair and body hair and ranges of make-up treatments.

Generaly, the plant cells of Buddleja davidii Franch. according to the present invention can be used in any form, in a linked form, incorporated or adsorbed on macro-, micro-, and nano-particles, or on macro-, micro- and nano-capsules, for the treatment of textiles, natural or synthetic fibers, wool, and all materials intended to come into contact with the skin and which can be used in clothing, day or night underwear, handkerchiefs, or fabrics, in order to exercise its cosmetic or therapeutic (dermatological) effect via this skin/textile contact and allow continuous topical delivery.

The CTFA ("International Cosmetic Ingredient Dictionary & Handbook" (19th Edition, 2019) published by "The Cosmetic, Toiletry, and Fragrance Association, Inc.", Washington, DC) describes a wide variety, without limitation, of cosmetic ingredients usually used in the skincare industry, which are suitable for use as additional ingredients in the compositions of the present invention.

Other additional skin care actives that are particularly useful can be found in Sederma's commercial literature and at www.sederma.com or www.crodarom.com.

The following commercial actives can also be mentioned as examples: betain, glycerol, Actimoist Bio 2™ (Active organics), AquaCacteen™ (Mibelle AG Cosmetics), Aquaphyline™ (Silab), AquaregulK™ (Solabia), Carciline™ (Greentech), Codiavelane™ (Biotech Marine), Dermaflux™ (Arch Chemicals, Inc), Hydra'Flow™ (Sochibo), Hydromoist L™ (Symrise), RenovHyal™ (Soliance), Seamoss™ (Biotech Marine), Argireline™ (commercial name of acetyl hexapeptide-3 from Lipotec), spilanthol or an extract of Acmella oleracea known under the trade name Gatuline Expression™, an extract of Boswellia serrata known under the name Boswellin™, Deepaline PVB™ (Seppic), Syn-AKE™ (Pentapharm), Ameliox™, Bioxilift™ (Silab), PhytoCellTec™Argan (Mibelle), Papilactyl D™ (Silab), Preventhelia™ (Lipotec), or one or more of the following active ingredient sold by Sederma : Subliskin™, Venuceane™, Moist 24™, Vegesome Moist 24™, Essenskin™, Juvinity™, Revidrat™, Resistem™, Chronodyn™, Kombuchka™, Chromocare™, Calmosensine™, Glycokin factor S™, Biobustyl™, Idealift™, Ceramide 2™, Ceramide A2™, Ceramide H03™, Legance™, Intenslim™, Prodizia™, Beautifeye™, Pacifeel™, Zingerslim™, Meiritage™, Senestem™, Sebuless™, Majestem™, Apiscalp™, Rubistem™, Citystem™, Neonyca™, NG Insaponifiables de Beurre de Karite™, Majestem™, Hydronesis™, Poretect™, Crystalide™, or mixture thereof. It is for example particularly advantageous to supplement or potentiate the action of the plant cells of Buddleja davidii Franch. according to the present invention with the action of a product acting on the presence of skin pigments of blood origin (such as biliverdin or bilirubin) responsible in particular for dark circles, for example N-hydroxysuccinimide (NHS) and/or chrysin. By way of examples, mention may be made of the commercial product Haloxyl™ marketed by the Applicant comprising a combination of NHS and chrysin and two matrikines, Pal-GHK and Pal-GQPR.

The association with a product acting on the radiance or the lightening of the complexion can also be mentioned such as for example the commercial products Lumisphere™ (a combination of diacetylboldine (DAB) encapsulated in microcapsules of polymethylmethacrylate and TiCEMn), Lumiskin™ (DAB in solution in triglycerides C8 CIO) or Mediatone™ (comprising octadecene dioic acid).

Among plant extracts (in the form of classical plant extracts or prepared by an in vitro process) that can be combined with plant cells of Buddleja davidii Franch. according to the present invention, there may more particularly be mentioned extracts of Ivy, in particular English Ivy ( Hedera helix), of Bupleurum chinensis, of Bupleurum falcatum, of arnica ( Arnica montana L), of rosemary {Rosmarinus officinalis N), of marigold {Calendula officinalis), of sage {Salvia officinalis L), of ginseng {Panax ginseng), of ginko biloba, of St.-John's-Wort {Hyperycum perforatum), of butcher's- broom {Ruscus aculeatus L), of European meadowsweet {Filipendula ulmaria L), of big- flowered Jarva tea {Orthosiphon stamincus benth), of artichoke {Cynara scolymus), of algae {Fucus vesiculosus), of birch {Betula alba), of green tea, of cola nuts {Cola nipida), of horse-chestnut, of bamboo, of Centella asiatica, of heather, of fucus, of willow, of mouse-ear, of escine, of cangzhu, of Chrysanthellum indicum, of the plants of the Armeniacea genus, Atractylodis platicodon, Sinnomenum, Pharbitidis, Flemingia, of Coleus such as C. Forskohlii, C. blumei, C. esquirolii, C. scutellaroides, C. xanthantus and C. Barbatus, such as the extract of root of Coleus barbatus, extracts of Ballote, of Guioa, of Davallia, of Terminalia, of Barringtonia, of Trema, of Antirobia, Cecropia, Argania, Dioscoreae such as Dioscorea opposita or Mexican, extracts of Ammi visnaga, of Siegesbeckia, in particular Siegesbeckia orientalis, vegetable extracts of the family of Ericaceae, in particular bilberry extracts {Vaccinium angustifollium) or Arctostaphylos uva ursi, aloe vera, plant containing sterols (e.g., phytosterol), Manjistha (extracted from plants of the genus Rubia, particularly Rubia cordifolia), and Guggal (extracted from plants of the genus Commiphora, particularly Commiphora mukul), kola extract, chamomile, red clover extract, Piper methysticum extract (Kava Kava™ from Sederma), Bacopa monieri extract (Bacocalmine™ from Sederma) and sea whip extract, extracts of Glycyrrhiza glabra, of mulberry, of melaleuca (tea tree), of Larrea divaricata, of Rabdosia rubescens, of Euglena gracilis, of Fibraurea recisa Hirudinea, of Chaparral Sorghum, of sun flower extract, of Enantia chlorantha, of Mitracarpe of Spermacocea genus, of Buchu barosma, of Law sonia inermis L. , of Adiantium capillus-veneris L. , of Chelidonium majus, of Luffa cylindrica, of Japanese Mandarin ( Citrus reticulata Blanco var. unshiu), of Camelia sinensis, of Imperata cylindrica, of Glaucium Flavum, of Cupressus sempervirens, of Polygonatum multiflorum, of Loveyly hemsleya, of Sambucus nigra, of Phaseolus lunatus, of Centaurium, of Macrocystis pyrifera, of Turnera diffusa, of Anemarrhena asphodeloides, of Portulaca pilosa, of Humulus lupulus, of Coffea arabica, of Ilex paraguariensis, or of Globularia cordifolia, of Albizzia julibrissin, of Oxydendron arboretum, of Zingimber zerumbet smith, of Astragalus membranaceus , of Atractylodes macrocephalae, of Plantago lanceolata, of Leontopodium alpinum, of Mirabilis jalapa, of Marrubium vulgare, of Apium graveolens or of orchids.

The compositions of the present invention may include one or more additional peptides, including, without limitation, di-, tri-, tetra-, penta-and hexapeptides and their derivatives. According to a particular embodiment, the concentration of the additional peptide, in the composition, ranges from lxl0 ⁷% and 20%, preferably from lxl0 ⁶% and 10%, preferably between lxl0 ⁵% and 5% by weight. The term“peptide” refers here to peptides containing 10 amino acids or less, their derivatives, isomers and complexes with other species such as a metal ion (e.g. copper, zinc, manganese, magnesium, and others). The term "peptides" refers to both natural peptides and synthetic peptides. It also refers to compositions that contain peptides and which are found in nature, and/or are commercially available.

Suitable dipeptides for use herein include but are not limited to Camosine (bAH), YR, VW, NF, DF, KT, KC, CK, KP, KK, TT, PA, PM or PP.

Suitable tripeptides for use herein include, but are not limited to RKR, HGG, GKH, GHK, GGH, GHG, KGH, KHG, KFK, KAvaK, KbAK, KAbuK, KAcaK, KPK, KMOK, KM0₂K (M0₂ being a di- oxygenated sulfoxide methionine), KVK, PPL, PPR, SPR, QPA, LPA, SPA, K(Ac)HG or K(Ac)GH, K(Ac) being a lysine with the amine function of the lateral chain acetylated, as disclosed in WO2017/216177, K(P)HG or K(P)GH, K(P) being a lysine with its lateral chain grafted with a proline, K(Pyr)HG or K(Pyr)GH, K(Pyr) being a lysine with its lateral chain grafted with a pyroglutamic acid, K(Hyp)HG or K(Hyp)GH, K(Hyp) being a lysine with its lateral chain grafted with a hydroxyproline, as disclosed in WO2016/097965.

Suitable tetrapeptides for use as additional peptides herein include but are not limited to RSRK (SEQ ID NO: 5), GQPR (SEQ ID NO: 6), KTFK (SEQ ID NO: 7), KTAK (SEQ ID NO: 7), KAYK (SEQ ID NO: 9) or KFYK (SEQ ID NO: 10).

A suitable non limitative example of pentapeptide is the KTTKS (SEQ ID NO: 11) and of hexapeptides the GKTTKS (SEQ ID NO: 12) and VGVAPG (SEQ ID NO: 13). Other suitable peptides for use according to the present inventin can be selected, this list being not limitative, from: lipophilic derivatives of peptides, preferably palmitoyl (Pal) derivatives or myristoyl (Myr), and metal complexes as aforementioned (e.g. copper complex of the tripeptide HGG or GHK). Preferred dipeptides include for example N-Palmitoyl- -Ala-His, N-Acetyl-Tyr- Arg-hexadecylester (Calmosensine™, Idealift™ from Sederma), Pal-RT or Pal-KT (from Sederma). Preferred tripeptide derivatives include for example Pal-GKH and Pal-GHK (from Sederma), the copper derivative of HGG (Lamin™ from Sigma), Lipospondin (N-Elaidoyl-KFK) and its analogs of conservative substitution, N-Acetyl-RKR-MF (Peptide CK+), N-Biot-GHK (from Sederma), Pal- KAvaK, Pal-K AlaK, Pal-KAbuK, Pal-KAcaK, or Pal-KMCEK (Matrixyl®synthe’6® from Sederma), Pal-KVK (Syn-Coll™ of DSM), and derivatives thereof.

Mention may also be made here of the anti -aging tripeptides of general Formula X-Pro*-Pro*-Xaa- Y described in WO2015181688 application with Xaa selected from Feu, Arg, Fys, Ala, Ser, and Asp, at the N-terminus , X chosen from H, -CO-R¹ and -SO2-R¹ and at the C-terminal end Y chosen from OH, OR¹, N¾, NHR¹ or NR' R². R¹ and R² being, independently of one another, chosen from a alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and/or sulfurized, said group possibly possessing in its backbone a heteroatom particularly O, S and/or or N, and Pro* corresponding to Proline, an analogue or derivative thereof; comprising, for example, Myr-PPF-OH and Myr-PPR-OH.

Here can further be cited also the propigmenting and/or pro-mec dipeptides and tripeptides of general Formula X-(Xaai)n-Pro*-Xaa2-Y disclosed in WO2014/080376, with n=0, 1 or 2, Xaai an hydrophobic aminoacid selected from Ala, Val, Met, Feu, Iso, Phe, Pro, and analogs and derivatives thereof; or a polar aminoacid selected from Ser, Thr, Tyr, Asp, Glu and analogs and derivatives thereof; and when n=2 the two aminoacids Xaai being the same or different; Xaa2 being an hydrophobic aminoacid selected from Ala, Val, Met, Feu, Iso, Phe, and analogs and derivatives thereof, or a basic aminoacid selected from Arg, Fys, His, and analogs and derivatives thereof; at the N terminal end X being selected from H, -CO-Ri and -SO2-R1; at the C terminal end Y being selected from OH, ORi, N¾, NHRi or NR1R2; Ri and R2 being, independently from each other, selected from an alkyl, aryl, aralkyl, alkylaryl, alkoxy et aryloxy group, that can be linear, branched, cyclic polycyclic, saturated, unsaturated, hydroxylated, carbonylated, phosphorylated and/or sulfured, said group having or not an O, S and/or N heteroatom in its skeleton and Pro* corresponding to a Proline, analog or derivative thereof; comprising for example the following peptides Pal-SPR-OH, Pal-PPR- OH, Pal-QPA-OH, Pal-FPAOH, Myr-SPA-OH, Pal-PM-OH, Pal-PA-OH and Pal-PP-OH.

Suitable tetrapeptide derivatives for use as additional peptides according to the present invention include, but are not limited to, Pal-GQPR (SEQ ID NO: 3) (from Sederma), Pal-KTFK (SEQ ID NO: 4) 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 herein include, but are not limited to, Pal-KTTKS (SEQ ID NO: 2) (available as Matrixyl® from Sederma), Pal-YGGFXaa (SEQ ID NO: 18) with Xaa being Leu or Pro, or mixtures thereof

Suitable hexapeptide derivatives for use herein include, but are not limited to, Pal-VGVAPG (SEQ ID NO: 1), Pal-GKTTKS (SEQ ID NO: 19), Pal-HLDIIXaa with Xaa being Trp, Phe, Tyr, Tic, 7- hydroxy-Tic ou Tpi (SEQ ID NO: 20) and derivatives thereof. The mixture of Pal-GHK and Pal- GQPR (SEQ ID NO: 3) (Matrixyl® 3000, Sederma) can also be mentioned.

The preferred compositions commercially available containing a tripeptide or a derivative include Biopeptide-CL™, Maxilip™, Biobustyl™, Procapil™ and Matrixyl®synthe’6® of Sederma. The compositions commercially available preferred sources of tetrapeptides include Rigin™, Eyeliss™, Matrixyl® Reloaded and Matrixyl 3000® which contain between 50 and 500 ppm of Pal-GQPR (SEQ ID NO: 3) and an excipient, proposed by Sederma.

The following marketed peptides can be mentioned as well as additional active ingredients:

Vialox™ (INCI name = Pentapeptide-3 (synthetic peptide comprising alanine, arginine, isoleucine, glycine and proline)), Syn-ake™ (b-Ala-Pro-Dab-NH-Bzl) or Syn-Coll™ (Pal-Lys- Val-Lys-OH) sold by Pentapharm;

Argireline™ (Ac-Glu-Glu-Met-Gln-Arg-Arg-NEE (INCI name = Acetyl hexapeptide-3) (SEQ ID NO: 21), Leuphasyl™ (Tyr-D-Ala-Gly-Phe-Leu) (SEQ ID NO: 22), Aldenine™ (Gly-His- Lys), Trylagen™ (INCI name = Pseudoalteromonas Ferment Extract, Hydro lyzed Wheat Protein, Hydro lyzed Soy Protein, Tripeptide- 10 Citrulline (reaction product of Citrulline and Tripeptide- 10 (synthetic peptide constituted of aspartic acid, isoleucine and lysine)), Tripeptide- 1), Eyeseryl™ (Ac- -Ala-His-Ser-His)(SEQ ID NO: 23), Serilesine™ (Ser-Ile-Lys-Val-Ala- Val) (SEQ ID NO 24) or Decorinyl™ (INCI name: Tripeptide-10 Citrulline = reaction product of Citrulline and Tripeptide- 10 (synthetic peptide constituted of aspartic acid, isoleucine and lysine) sold by Lipotec;

Collaxyl™ (Gly-Pro-Gln-Gly-Pro-Gln (SEQ ID NO 25)) or Quintescine™ (Cys-Gly) sold by Vincience;

Cytokinol™LS (casein hydrolysate) sold by Les Laboratoires Serobiologiques/Cognis;

Kollaren™ (Gly-His-Lys), IP2000™ (Pal-Val-Tyr-Val) or Meliprene™ (INCI name = Monofluoroheptapeptide-1: reaction product of acetic acide and a synthetic peptide comprising arginine, glycine, glutamic acid, histidine, norleucine, p-fluorophenylalanine and tryptophan) sold by Tlnstitut Europeen de Biologie Cellulaire; Neutrazen™ (Pal-His-D-Phe-Arg-MT) sold by Innovations; or

BONT-L-Peptide™ (INCI name = Palmitoyl Hexapeptide-19: reaction product of palmitic acid and Hexapeptide-19 (synthetic peptide constituted of asparagine, aspartic acid, lysine and methionine), Timp-Peptide™ (INCI name = Acetyl Hexapeptide-20: reaction product obtained by acetylation of Hexapeptide-20 (synthetic peptide constituted of alanine, glycine, lysine, valine and proline) or ECM Moduline™ (INCI name = Palmitoyl Tripeptide-28: reaction product of palmitic acid and Tripeptide-28 (synthetic peptide constituted of arginine, lysine and phenylalanine) sold by lnfmitec Activos.

It is also possible to combine the plant cells according to the invention with one or more cyclic peptides, in particular those extracted from linseed oil described in the patent application of the Applicant FR1850845.

According to the invention, by "topical treatment" or "topical use" means an application which is intended to act in the place where it is applied: skin, mucous membrane, skin appendages.

Plant cells from Buddleja davidii Franch. according to the invention or the composition according to the invention comprising them, can be applied locally to the targeted areas.

The "effective" amount depends on various factors, such as age, the cutaneous state of the user, the intensity of the disorder and the mode of administration. An effective amount means a non-toxic amount sufficient to achieve the desired effect, in particular a more or less pronounced effect. This effective amount according to the invention is more detailed below (point B).

All percentages and ratios used in this application are by weight of the total composition and all measurements are made at 25°C, unless otherwise specified.

For example, for a cosmetic facial treatment, the European Cosmetics Directive has set a standard application amount of a cream of 2.72 mg/cm²/day/person and for a body lotion of 0.5 mg/cm²/day/person.

According to other features, the cosmetic treatment method according to the invention can be associated with one or more other treatment methods aimed at the skin, such as, for example, light therapy, heat, vibration, electroporation treatments, micro-needle patch, or aromatherapy.

According to the invention, devices can be proposed with several compartments or kits intended for the implementation of the method described above, and which could include, by way of example, and without being limiting, in a first compartment a composition comprising an active ingredient according to the invention based on plant cells of Buddleja davidii Franch. and in a second compartment an excipient and/or additional active, the compositions contained in said first and second compartments being here considered as a combination composition for simultaneous, separate or spread over time use especially in one of the treatments defined above.

DETAILED DESCRIPTION

The present invention will be better understood in the light of the following detailed description of embodiments.

A) Example of in vitro preparation of a plant cell extract according to the invention

1. Creation of a cell line

Selected leaves of the Buddleja davidii Franch. plant are collected, washed and cut into small pieces of a few mm, so as to produce numerous explants. After a series of decontamination treatments, the pieces are placed on a panel of agar culture media, in order to induce callogenesis (formation of a callus).

After an appropriate period, a cluster of dedifferentiated cells or cal forms, which is transferred to a larger volume of new culture medium in order to be able to multiply. A certain number of subcultures (transfers to a fresh culture medium) are carried out to stabilize the cell line, that is to say until it presents a satisfactory and constant proliferation rate, a conservation phenotype, a constant content of bioactive compounds of interest (primary and secondary metabolites).

The cell line is then subjected to a selection step which consists in culturing the cells for an appropriate duration, in taking the cell aggregates formed and inoculating them in a liquid culture medium for a duration allowing the multiplication of 1 cell aggregate. The best cell line will be that which allows a satisfactory biomass having an optimal content of selected metabolites, the best biological activity and a homogeneous phenotype to be obtained as quickly and as reproducibly.

This cell line was also chosen for its ability to produce the maximum amount of verbascoside.

2. Industrial process for obtaining a biomass of undifferentiated or dedifferentiated cells from Buddleja davidii Franch. and treatment of this biomass

A cell line prepared as described above or from an existing line is used.

The line of Buddleja davidii Franch. is first multiplied to obtain enough quantity of dedifferentiated cell biomass to perform the large-scale production step.

The following steps are implemented:

a) Inoculation of the selected line in a liquid medium, and culture for enough time to obtain an increase of the biomass of at least 300%;

b) Optionally, transfer of the suspension obtained in a) into a fresh liquid medium, and culture again for enough time to obtain an increase of the biomass of at least 300%; c) Optionally, repeat step b);

d) Transfer of the cell suspensions obtained in stages a) to c) in a bioreactor with fresh liquid medium, and culture carried out under such conditions and for a time sufficient to obtain a cellular biomass containing the metabolites of interest that is to say the phenylpropanoids glycosides including the verbascoside in sufficient quantities, this stage of production in bioreactor comprising a stage of elicitation carried out by modifying the levels of nutrients of the culture medium.

The bioreactor:

Volume: 5 to 50 times greater than the volume of biomass used as an inoculum; smooth and uniform internal surface of the bioreactor (no edges or angles that can cause cell walls to rupture).

Culture conditions:

Culture medium: medium comprising mineral salts (solution of macroelements and microelements), vitamins, plant hormones and sucrose. Vegetable agar is added to the solid media for the initial stages.

Temperature: between 15°C and 35°C.

Duration: between 7 and 21 days with agitation of the biomass so that it is optimally aerated.

Oxygenation: usually performed using sterile air or mixtures of gases containing 10% to 100% v/v oxygen.

Treatment of the obtained biomass:

Filtration to remove the culture medium and recover the cell biomass. This biomass can be characterized by its equivalent rate of lyophilized cells.

Characterization of the active compounds contained in the cells by analytical determination of primary and secondary metabolites produced by the culture including the content of proteins, phenylpropanoids glycosides including the verbascoside.

Homogenization under high pressure of cellular biomass: allows a reduction in the size of cellular aggregates; some cells can be ruptured and a mixture of whole cells and lysed cells can be obtained, comprising in general about 50% of whole cells.

Optionally:

1) Drying of the cells, for example by lyophilization or atomization, to allow greater stability of the compounds of interest, improve long-term storage without having to add preservatives. 2) Extraction of the cell contents by grinding/lysis/bursting of the cells and separation of the liquid and solid phases (by centrifugation or fdtration or other), in order to obtain a specific cell extract.

3) Purification of the cell extract to increase the verbascoside content.

B) Preparation of an active ingredient according to the invention for a use according to the invention

The plant material is mixed with a physiologically acceptable medium forming the excipient.

In the case of a plant material obtained by cell culture in vitro as described above in point A), as a preferred example, this physiologically acceptable medium is, according to the invention, a hydrophilic matrix in which the plant cells whole or exploded are suspended. In the case of a cosmetic composition, the hydrophilic matrix consists, for example, of glycerol and/or butylene glycol.

An active ingredient for cosmetic use can thus be formed for the implementation of the invention, comprising for example 20% by weight of cellular extract of fresh biomass of whole dedifferentiated cells (corresponding to approximately 1-2% of dry cells), in a physiologically acceptable excipient mixture consisting of glycerol (approximately 80%), said ingredient containing between 0.2% and 0.5% of phenylpropanoids with predominantly verbascoside. This ingredient can then be used to prepare cosmetic formulations such as that the example given below in Galenic point F). An effective amount represents between 0.3% and 15%, preferably between 1% and 5%, more preferably between 2% and 4% and generally 3% by weight of said formulation.

In the scope of the invention, a plant material comprising a different rate of phenylpropanoids (and in particular of verbascoside), in particular higher, could be used, either obtained directly by the in vitro process (for example thanks to another elicitation allowing to increase this rate), or obtained by a purification/concentration phase after extraction of the cellular content.

C) GALENIC

The following cream formula 1 is given by way of example in the following table 1 :

Table 1

D) In vitro EFFICACY TESTS

1. Tests showing the lightening effect

Reduction in melanin production, residual tyrosinase activity and expression of dopachrome tautomerase (mRNA).

Protocol:

Three trials were conducted to evaluate the effect of the ingredient according to the invention on moderately pigmented normal human melanocytes (NHM) (isolated from a moderately pigmented donor). The NHM at confluence were brought into contact with the ingredient according to the invention for 6 or 11 days. The ingredient according to the invention has been tested at 0.5%, 1% and 2%. At the end of the contact, melanins are extracted from cells after crushing and measured by spectrophotometry. An estimate of the number of cells is also carried out at the end of the culturing using a protein assay by the BCA method. Melanin concentrations are standardised to the quantity of proteins of the sample.

The residual tyrosinase activity is measured in the ground cells; the results being standardised to the quantity of proteins of the sample. For dopachrome tautomerase (DCT), it was chosen to look at the expression of its gene in NHM brought in contact with the ingredient according to the invention by following the production of its messenger RNA (mRNA).

Results

Effect of the ingredient according to the invention on melanin production NHM (n=4); 11 days of contact:

Table 2

Positive control: arbutin at 300 ppm: -49% (p<0.01).

Effect of the ingredient according to the invention on the residual tyrosynase activity of NHM (n=4); 6 days of contact:

Table 3

Positive control: arbutin at 300ppm: -75% (p<0.01).

Effect of the ingredient according to the invention on the expression of DCT mRNA in NHM (n=3):

Table 4

The results show that the ingredient according to the invention decreases melanin production in a dose-dependent and significant way (-31% to -42%), without a cytotoxic effect on these cells despite a long contact time. Furthermore, the tyrosinase activity of the NHM after contact with the ingredient according to the invention is also reduced in a dose-dependent way (-19% to -47%). Finally, the expression of mRNA of DTP is also reduced in a dose-dependent manner (-44% and -53%).

A direct action of the ingredient according to the invention on the activity of tyrosinase and on the production of the DPC enzyme is therefore noticed, thus allowing to control the pigmentation of the melanocyte and to reduce the overall production of pigments of these cells strongly producing melanins, this without toxicity for these cells deemed to be fragile.

Reduction of phagocytosis of melanosomes.

Principle

The increase in skin pigmentation is linked in particular to a greater transfer of melanosomes loaded with melanin from the melanocyte to the surrounding keratinocytes. Moderation of this phagocytosis is known to promote skin lightening.

Protocol

Normal human keratinocytes (NHK) at confluence are brought into contact with the ingredient according to the invention and then receive a solution of artificial fluorescent melanosomes in the form of beads to measure their capacity to include these fluorescent structures. After rinsing to remove the non-phagocytosed beads, photographs are taken by fluorescence microscopy and are analyzed by image analysis. The number of cells is estimated using the Hoescht 33258 method and used to standardise the results.

Results

Effect of the ingredient according to the invention on phagocytosis by NHK of melanosome mimes (n = 3; 27 photos/case):

Table 5

The results show that the phagocytosis by the NHK of the melanosome models can be effectively moderated by 32% and 44% thanks to the ingredient according to the invention (both p<0.01). Thus, in addition to its action on the overall activity of tyrosinase, by the expression of DPC and on the production of melanin, the ingredient according to the invention markedly reduces the phagocytosis of melanosomes by NHK, cells associated with melanocytes. These elements indicate that the ingredient according to the invention promotes the lightening of the skin.

2. Test showing an anti-glycation effect

Principle

AGEs decrease the quality of hyaluronic acid and have recently been implicated in inducing melanogenesis.

Protocol

The anti-glycation effect of the ingredient according to the invention was evaluated in a test using a model protein (BSA) and a reducing sugar (fructose). This mixture is incubated to create AGEs which are observed and quantified by fluorescence. The production of AGEs in the presence of the ingredient according to the invention is compared with that obtained with the control.

Results

Effect of the ingredient according to the invention on the production of AGEs (n = 4):

Table 6

These results show the high anti-glycant potential of the ingredient according to the invention, which can reduce the formation of AGEs, at the lowest concentration tested, and potentially can control their effects on dull skin, denaturation of proteins and hyaluronic acid.

3. Test showing an effect on skin barrier reinforcement

Protocol

HK or NHK are cultivated at sub-confluence and are then brought into contact with the ingredient according to the invention. At the end of this contact, the cells are rinsed, fixed and labeled with antibodies directed against involucrine, an essential component of the barrier function of the epidermis and against cytokeratin-1, a tracer of differentiation of the epidermis. An estimation of the quantity of cells by Hoechst method is used to standardise the results. Results

Effect of the ingredient according to the invention on the production of involucrine and cytokeratin- 1 by NHK (n = 3; 27 photos/case):

Table 7

These results show that the ingredient according to the invention stimulates the production of involucrine and cytokeratin-1, essential elements for the barrier function of the epidermis.

4. Test showing an effect on the stimulation of hyaluronic acid

Protocol

HK are cultivated at sub-confluence and then brought into contact with the ingredient according to the invention. Following this contact, the culture supernatants are assayed for their hyaluronic acid content using an ELISA type assay. An estimation of the quantity of cells by Hoechst method is used to standardise the results.

Results

Modulation of hyaluronic acid production by keratinocytes in contact with the ingredient according to the invention:

Table 8

Positive control: retinoic acid ImM: +184% (p<0.01).

These results show that the ingredient according to the invention strongly stimulates the production of hyaluronic acid in the keratinocyte. This increase reaches +240% (p<0.01 ). This therefore contributes to the homeostasis of the epidermis and to improving its qualities. 5. Test showing an effect on the strengthening of the dermo-epidermal junction Protocol

HK are cultivated at sub-confluence and then brought into contact with the ingredient according to the invention. At the end of this contact, the culture supernatants and the cell mats are assayed respectively for their laminin and collagen-VII content, respectively using ELISA-type kits. An estimation of the quantity of cells by Hoechst method is used to normalize the results.

Explants of human skin (woman, Caucasian, 29 years, phototype III) received daily applications of a cream containing 2% of the ingredient according to the invention or a placebo cream (once/day/7 days; cream 1 in the galenical part in point B) above). After this contact, the skins are rinsed, frozen before being sectioned in the microtome and marked for collagen-VII or laminin-5. Five explants are produced for each case. Photos of the sections are taken under a fluorescence microscope to quantify the intensity of the labelling.

Effect of the ingredient according to the invention on the production of collagen-VII (carpets) and laminins (supernatants) by NHK (n=4):

Table 9

nsd: nonsignificant difference

Effect of the ingredient according to the invention on the production of collagen-VII and laminin 5 by skin explants (n=5 explants; 12 photos/section; 60 photos/case):

Table 10

These results show that the ingredient according to the invention stimulates the production of collagen-VII and laminins, essential elements for the dermo-epidermal junction, these results being observed on a model of cells in culture and on a more complex model and realistic of explants. E) COMPARATIVE in vitro EFFICACY TESTS WITH THE VERBASCOSIDE ALONE - Effect on pigmentation

Inhibition of melanin synthesis on human melanocytes

Protocol

Normal human melanocytes are seeded and cultivated in their maintenance medium, then brought into contact with the products to be tested in the test medium for 11 days. The product according to the invention has been tested at 1% and 2%; the verbascoside is tested in parallel at doses equivalent to those present in the product according to the invention (i.e. 30 and 60 ppm respectively). After contact, the melanins are extracted from the cells and assayed spectrophotometrically (490 nm). The number of cells is estimated at the end of the culture using a protein assay by the BCA method. Melanin concentrations are normalized by the protein content of the sample.

Results

Inhibition of melanogenesis compared to control, after 11 days of contact with the products to be tested:

Table 11

Inhibition of tyrosinase activity on human melanocytes

Protocol

Normal human melanocytes are seeded and cultivated in their maintenance medium, then brought into contact with the products to be tested in the test medium for 11 days. The product according to the invention is tested at 1% and 2%; the verbascoside is tested in parallel at doses equivalent to those present in the product according to the invention (i.e. 30 ppm and 60 ppm respectively). After contact, the residual tyrosinase activity is measured in the grounded cells. The number of cells is estimated at the end of the culture using a protein assay by the BCA method. Tyrosinase activity is normalized by the protein content of the sample. Results

Inhibition of tyrosinase activity compared to control, after 11 days of contact with the tested products

Table 12

It is surprisingly observed that the ingredient according to the invention gives better results both on the inhibition of melanogenesis and that of tyrosinase than pure verbascoside at doses equivalent to those present in the product according to the invention.

The lightening activity of the product according to the invention cannot therefore be explained by the mere presence of the verbascoside.

F) In-vivo EFFICACY TESTS

Tested product: The cream 1) of above galenic point C).

Principles: The evaluation of the effectiveness of the cream was carried out on a panel of female volunteers living in Tunisia and of the Middle Eastern type. The study was conducted versus placebo and aimed to measure the improvement of skin radiance using the following two complementary techniques:

• an evaluation of the skin texture, performed with a VISIA® system; and

• an evaluation of the skin colour, performed on different areas of the face by image analysis on standardised photographs.

Protocol:

Special inclusion criteria

The study was conducted on a panel of 26 women (mean age: 36 years [23-58]), of phototype IV and having imperfect skin, namely having a dull complexion, dark circles, an irregular skin texture, and areas of hyperpigmentation. The volunteers had to avoid excessive sunlight (natural or artificial) 1 month before the start of the test. Type of study duration product applications

For 1 month, the volunteers applied to the face morning and evening a cream according to the invention and a placebo cream on opposite sides of the face. A cream containing a sunscreen (SPF50) was also provided to the volunteers for daily use in order to limit the perturbative effect of the sun, the volunteers also having to avoid sun exposure without protection.

Statistics

Statistical studies were performed using the Student /-test, or if necessary, with a non-parametric Wilcoxon test. Uni- or bilateral tests were carried out on matched series, which was possible thanks to the applications in contralateral. In the case of self-evaluations, Khi² tests were used.

Method and results

Skin texture evaluation

Principle:

A Visia® CAS device (Canfield, USA) was used, allowing standardised photos to be obtained under different illuminations (white, UV, polarised light) with an integrated software that can provide different parameters. The elevations (in one colour) and the depressions (in another colour) are assimilated to a roughness of the skin and the measurement of the colour heterogeneity between these two areas made it possible to measure the texture of the skin.

Results:

Variation of the texture on the face after application of the cream according to the invention (n=26 volunteers); values in arbitrary units:

Table 13

After 1 month of application of the cream according to the invention, the face has fewer visible imperfections and has therefore become smoother. Compared to the placebo application, the improvement reaches +6% and is significant with p<0.05. Evaluation of the skin colour

Principle:

The same device as previously (VISIA®) was used to obtain photographs of the face in cross- polarised mode in order to remove the natural skin shine. The technology developed by Newtone (France) to extract the parameters and analyze the colour parameters before and after application was applied. The measurements were taken on the cheek.

The parameters studied are those of the CIE L*a*b* system:

• L* : an increase in L* demonstrates an increase in the skin luminosity,

• a* : a decrease in a* demonstrates a reduction in redness,

• ITA° (« Individual Typologic Angle »): an increase in ITA° demonstrates depigmentation (lightening) of the skin (lower pigmentation in skin), and

• IWA° (« Individual Whithening Angle »): an increase in IWA° demonstrates a brightening effect.

The observation of the panel shows that the possible amplitude of these parameters is around 20 units, L* being between 45 and 65, a* being between 15 and 35, ITA° being between 0 and 30 and IWA° being between 45 and 65.

Results:

Variation of the parameters of the complexion (colour) on the face after application of the cream according to the invention or the placebo cream; (n = 26 volunteers); values in arbitrary units:

Table 14

The analysis of these data and of the photos concerning the parameters related to the skin complexion (colours) show an improvement in the skin complexion in favor of the applications carried out with the cream according to the invention compared to the placebo cream. The effect is clear since there is a better luminosity (+5%, p<0.01), a better depigmentation (+8.5%, p<0.01) and a better brightening effect (+3 %,p<0.01). Regarding the redness, measured on the cheeks, the improvement is noted with a significant decrease of 2% significant with probability p<0.075.

Claims

1. Use of undifferentiated or dedifferentiated plant cells, whole and/or lysed, of Buddleja davidii Franch. obtained by an in vitro cell culture process, and/or an intracellular extract of said cells free of cellular debris, for a topical non-therapeutic cosmetic treatment to homogenize skin complexion.

2. Use according to claim 1, characterized in that the cells are used in the form of a mixture of whole cells and lysed cells suspended in a physiologically acceptable medium.

3. Use according to claim 2, characterized in that the physiologically acceptable medium is a hydrophilic matrix.

4. Use according to any one of claims 1 to 3, characterized in that the treatment is adapted for preventing and/or treating pigmentary and/or texture heterogeneities of the skin.

5. Use according to any one of claims 1 to 4, characterized in that the treatment is adapted for lightening the skin, for countering the glycation of proteins, for smoothing the skin, for stimulating the production of hyaluronic acid, for strengthening the skin barrier and/or for reinforcing the dermo-epidermal junction.

6. Use according to any one of claims 1 to 5, characterized in that the treatment is adapted for skins of phototype III to V.

7. Use according to claim 6, characterized in that the treatment is suitable for olive carnation skin tones.

8. Use of undifferentiated or dedifferentiated plant cells, whole and/or lysed, from Buddleja davidii Franch. obtained by an in vitro cell culture process, and/or an intracellular extract of said cells free of cellular debris, for the manufacture of an active cosmetic ingredient for homogenizing skin complexion and of a topical cosmetic composition comprising said active ingredient.

9. Use according to claim 8, characterized in that said active ingredient is adapted for preventing and/or treating pigmentary and/or skin texture heterogeneities.

10. Use according to claim 8 or 9, characterized in that said active ingredient is adapted for lightening the skin, for countering the glycation of proteins, for smoothing the skin, for stimulating the production of hyaluronic acid, for strengthening the skin barrier and/or for strengthening the dermo-epidermal junction.

11. Use according to any one of claims 8 to 10, characterized in that said active ingredient is adapted for the treatment of skins of phototype III to V.

12. Use according to claim 11, characterized in that said active ingredient is adapted for the treatment of olive skin tones.

13. Use of undifferentiated or dedifferentiated plant cells, whole and/or lysed, of Buddleja davidii Franch. obtained by an in vitro cell culture process, and/or an intracellular extract of said cells free of cellular debris, for preparing a cosmetic composition for a topical non- therapeutic cosmetic treatment to homogenize skin complexion.