WO2001043701A2 - Cosmetic or dermopharmaceutical compositions containing the n-palmytoyl-gly-hys-lys tripeptide - Google Patents

Cosmetic or dermopharmaceutical compositions containing the n-palmytoyl-gly-hys-lys tripeptide Download PDF

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WO2001043701A2
WO2001043701A2 PCT/FR2000/003236 FR0003236W WO0143701A2 WO 2001043701 A2 WO2001043701 A2 WO 2001043701A2 FR 0003236 W FR0003236 W FR 0003236W WO 0143701 A2 WO0143701 A2 WO 0143701A2
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Prior art keywords
cosmetic
tripeptide
compositions according
dermopharmaceutical compositions
gly
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PCT/FR2000/003236
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French (fr)
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WO2001043701A3 (en
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Karl Lintner
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Sederma
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/06—Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/645—Proteins of vegetable origin; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/57—Compounds covalently linked to a(n inert) carrier molecule, e.g. conjugates, pro-fragrances

Definitions

  • the cosmetic industry is constantly on the lookout for new ingredients capable of repairing the irreparable outrage for years, and therefore, minimizing the main stigmas of wrinkles, by delaying the appearance or reducing it. importance.
  • the invention which is the subject of this patent application resides in the fact that we have developed a product, the tripeptide, N-palmitoyl-Gly-His-Lys, which makes it possible to restore the concentration of a better collagen. quality, which, being new to the body itself, will erase or reduce the importance of wrinkles while ensuring perfect tolerance and painless to the user.
  • a non-N-acylated tripeptide must contain any possible association of amino acids found in thymulin or in thymopoietin AA (FR-95 13544) without the Gly-His-Lys sequence being mentioned, glycosylated and preferably linked to a metal atom such as zinc,
  • the tripeptides which are the subject of this patent application can be obtained either by conventional chemical synthesis (in heterogeneous phase or in homogeneous phase), or by enzymatic synthesis (Kullman et al., J. Biol. Chem. 1980, 255, 8234) from the constituent amino acids or their derivatives.
  • the small size of the tripeptide allows it to be synthesized industrially, at an advantageous cost. Its large demonstrated activity authorizes commercial use in a large number of financially acceptable cosmetic or dermopharmaceutical products.
  • the tripeptide can also be obtained by fermentation of a strain of bacteria, modified or not by genetic engineering, to produce the desired sequences or their different fragments.
  • the tripeptide can be obtained by extraction of proteins of animal or vegetable origin, preferably vegetable, capable of containing these sequences within their structure, followed by a controlled hydrolysis, enzymatic or not, which releases the peptide fragment of sequence Gly-His-Lys in plants which are likely to contain these sequences within their structure.
  • the controlled hydrolysis makes it possible to release these peptide fragments.
  • Example No. 3 Increased collagen synthesis: in vitro
  • explants originating from mammary or abdominal plasty, are incubated, for 72 hours in the presence of 3 H-proline, with the tripeptide in three final concentrations in the culture medium (1.10 "4 %, 3.10 " 4 % and 1.10 "3 %; is 1, 3 and 10 ppm).
  • the explants are then washed, the dermis and epidermis of each explant are separated, homogenized and lysed.
  • the measurement of the incorporation of 3 H-proline is then carried out in each lysate.
  • the tests are carried out in triplicate.
  • negative controls are carried out under the same conditions but in the absence of the tripeptide. Positive controls are made by replacing the tripeptide tested with vitamin C.
  • This example reports the anti-wrinkle effect obtained, in vivo, on a panel made up of 150 adult female volunteers, aged 35 to 63 years.
  • the anti-wrinkle power of the cream of Example 2, containing N-Palmitoyl-Gly-His-Lys, at a concentration of 0.005% (i.e. 50 ppm), is compared to that of a placebo cream (same cream but without the asset).
  • the creams are applied to precisely identified sites, located on the corner of the right or left eye, according to a randomized distribution, twice a day, for 28 days. This experiment was carried out according to a so-called double-blind protocol since neither the volunteer nor the experimenters knew the nature of the product applied.
  • the double-blind protocol further demonstrates the spectacular effect of the N-Palmitoyl-Gly-His-Lys tripeptide.
  • Example 6 Activity on the curve of the mouth: in vivo
  • the level of surface hydration was rated by the dermatologist in charge of the study; the volume measured by Toposkin ® (from two photos taken simultaneously from two different angles, an adapted software allows to restore the image in three dimensions and to make volumetric measurements).
  • the volunteers had to fill out questionnaires based on subjective criteria.
  • the following table shows the means (arbitrary units) and the standard deviations obtained at TO and T +30 days on the hydration evaluated at the level of the upper lip and the lower lip and on the labial flobal volume.
  • the self-assessment showed that an obvious improvement in the state of the lips (in 100% of volunteers), satisfaction with skin comfort (70%), a feeling of protection (70%), an improvement in roughness. (70%) and an improvement in scaling judged as moderate (40%) to large (20%).
  • the tripeptide of this patent, acylated or not can be obtained by chemical synthesis, by enzymatic way, by fermentation, by extraction of proteins of vegetable origin, by classic peptide synthesis in homogeneous or heterogeneous phase or by enzymatic synthesis starting from acids constituent amines.
  • the tripeptide of this patent, acylated or not, subject of this patent can be obtained by extraction of plant proteins, followed by hydrolysis, enzymatic or non-enzymatic, so as to generate peptide fragments of average size between 300 and 1500 daltons, part of the released fragments must contain the Gly-His-Lys sequence.
  • the tripeptide of this patent, acylated or not can be used at concentrations varying between 0.1 and 1000 ppm (w / w), preferably between 1 and 200 ppm (w / w) in the finished cosmetic or dermopharmaceutical product.
  • the tripeptide of this patent, acylated or not can be used in the form of a solution, dispersion, emulsion, or encapsulated in vectors such as macro-, micro- or nanocapsules, liposomes or chylomicrons, or included in macro-, micro- or nanoparticles, or in micro-sponges, or adsorbed on powdery organic polymers, talcs, bentonites and other mineral supports.
  • the tripeptide of this patent can be used in any galenical form: O / W and W / O emulsions, milks, lotions, gelling and viscosifying polymers, surfactants and emulsifiers, ointments, hair lotions, shampoos, soaps, powders , sticks and pencils, sprays, body oils.
  • the tripeptide of this patent, acylated or not can be used with any other ingredient usually used: extraction and / or synthetic lipids, gelling and viscosifying polymers, surfactants and emulsifiers, water or liposoluble active principles, plant extracts, extracts tissues, marine extracts, sun filters, antioxidants.
  • the tripeptide of this patent, acylated or not can be used in cosmetic applications to eliminate, reduce or prevent the appearance of wrinkles, whatever their location and cause.
  • the tripeptide of this patent, acylated or not can be used for the preparation of a medicament for eliminating, reducing or preventing the appearance of wrinkles, whatever their location and cause.

Abstract

The invention relates to the use of the N-palmytoyl-Gly-Hys-Lys tripeptide in cosmetic or dermopharmaceutical compositions. The tripeptide can be obtained by synthesis, biotechnology or controlled hydolysis of vegetable proteins. When said compositions are applied topically, they can eliminate, reduce or prevent wrinkles irrespective of location and cause and can improve the curve of the mouth.

Description

TITRE Compositions cosmétiques ou dermopharmaceutiques contenant le tripeptide N-palmytoyl-Gly-Hys-Lys, pour éliminer, réduire ou prévenir l'apparition de rides, qu'elles qu'en soient la localisation et la cause.TITLE Cosmetic or dermopharmaceutical compositions containing the tripeptide N-palmytoyl-Gly-Hys-Lys, to eliminate, reduce or prevent the appearance of wrinkles, whatever their location and cause.
Le vieillissement, notamment celui de la peau, entraîne d'importantes perturbations biochimiques tissulaires intimes qui se manifestent par des modifications macroscopiques, habituellement jugées disgracieuses, et qui n'ont cessé de préoccuper tant les femmes que les hommes: les rides.Aging, especially that of the skin, leads to significant intestinal biochemical tissue disturbances which are manifested by macroscopic modifications, usually considered unsightly, and which have not ceased to worry both women and men: wrinkles.
D'autres composants de notre mode de vie actuel, telles que les agressions physiques et chimiques de la pollution; la consommation d'alcool et de tabac favorisent et aggravent les processus de vieillissement. Il en est de même pour la perpétuelle quête du bronzage par les UV naturels ou artificiels, par le biais deOther components of our current way of life, such as the physical and chemical aggressions of pollution; alcohol and tobacco consumption promote and worsen the aging process. It is the same for the perpetual quest for tanning by natural or artificial UV, through
Yhéliodermie (Dr C. Musy-Preault, (1994)).Yheliodermia ( Dr. C. Musy-Preault, (1994)).
L'industrie cosmétique est en permanence à la recherche de nouveaux ingrédients capables de réparer des ans l'irréparable outrage, et donc, d'en minimiser les principales stigmates que sont les rides, en en retardant l'apparition ou en en diminuant l'importance.The cosmetic industry is constantly on the lookout for new ingredients capable of repairing the irreparable outrage for years, and therefore, minimizing the main stigmas of wrinkles, by delaying the appearance or reducing it. importance.
Il est maintenant certain que la diminution de la quantité et de la qualité de substance dans la matrice extracellulaire est la principale cause de l'apparition des rides. L'amélioration ou la reconstruction de la matrice extracellulaire est primordiale car l'on sait maintenant que non seulement cette structure joue "le rôle de charpente stabilisant la structure physique des tissus" mais qu'également, elle "Joue un rôleIt is now certain that the decrease in the quantity and quality of substance in the extracellular matrix is the main cause of the appearance of wrinkles. The improvement or reconstruction of the extracellular matrix is essential because we now know that not only does this structure play "the role of a framework stabilizing the physical structure of the tissues" but that it also "Plays a role
.... dans la régulation du comportement des cellules qui sont à son contact - influant sur leur développement, leur migration, leur prolifération, leur forme et leurs fonctions (Biologie Moléculaire de la Cellule, 3ème éd. Médecine-Sciences,.... in regulating the behavior of cells that are in contact - affecting their development, migration, proliferation, shape and function (Molecular Biology of the Cell, 3rd edition Medicine-Sciences.
Flammarion, Paris, 1997:972).Flammarion, Paris, 1997: 972).
Comme le collagène est le principal constituant de la matrice cellulaire, agir sur la quantité et la qualité du collagène tissulaire équivaut à agir, de manière bénéfique sur cette dernière. Dans le cadre de ce brevet, les effets du vieillissement sur les collagènes peuvent se résumer par:As collagen is the main constituent of the cell matrix, acting on the quantity and quality of tissue collagen is equivalent to acting in a beneficial way on the latter. In the context of this patent, the effects of aging on collagens can be summarized by:
- La diminution de sa synthèse par les fibroblastes, diminution due à la conjonction de deux causes: d'une part le taux de renouvellement de ces cellules productrices diminue avec l'âge et, d'autre part, la quantité de molécules sécrétées par ces cellules diminue également.- The decrease in its synthesis by fibroblasts, a decrease due to the conjunction of two causes: on the one hand the rate of renewal of these producer cells decreases with age and, on the other hand, the quantity of molecules secreted by these cells also shrinks.
Lorsque l'on sait que le collagène représente environ 80% des protéines cutanées, il est facile de comprendre que la moindre diminution de sa concentration tissulaire puisse avoir des conséquences importantes sur les propriétés mécaniques et physiologiques de la peau.When we know that collagen represents about 80% of skin proteins, it is easy to understand that the slightest decrease in its tissue concentration can have significant consequences on the mechanical and physiological properties of the skin.
- 'apparition de modifications structurales des molécules néo-synthétisées qui conduisent à la réticulation des fibres et donc, à leur rigidification.- 'appearance of structural modifications of the neo-synthesized molecules which lead to the crosslinking of the fibers and therefore, to their stiffening.
Pour le collagène, les variations des chaînes α modifient la répartition de ses différentes formes. Par exemple, la proportion de collagène de type El augmente dans l'épidémie quand le collagène de type IV s'accumule dans la membrane basale. On constate également l'apparition de réactions, enzymatiques ou non (de type réaction de Maillard), qui créent des liaisons, dites croisées, soit entre deux fibres de collagène, soit entre le collagène lui-même et des molécules de glucose, rigidifiant ainsi les réseaux de fibres de collagène. La peau perd donc de sa substance par la diminution de la quantité de ses constituants, se durcit par la perte d'élasticité des fibres de collagène et par sa déshydratation et ceci contribue à donner à la peau âgée ses aspects caractéristiques: absence de souplesse, finesse, fragilité, et surtout, rides plus ou moins nombreuses et plus ou moins profondes. Agir sur la quantité et sur la qualité du collagène cutané est donc la meilleure approche pour lutter contre les rides.For collagen, variations in the α chains modify the distribution of its different forms. For example, the proportion of type E1 collagen increases in the epidemic when type IV collagen accumulates in the basement membrane. We also note the appearance of reactions, enzymatic or not (of the Maillard reaction type), which create so-called crossed bonds, either between two collagen fibers, or between the collagen itself and glucose molecules, thus stiffening collagen fiber networks. The skin therefore loses its substance by the decrease in the amount of its constituents, hardens by the loss of elasticity of the collagen fibers and by its dehydration and this contributes to giving the aged skin its characteristic aspects: absence of flexibility, finesse, fragility, and above all, more or less numerous and more or less deep wrinkles. Acting on the quantity and quality of skin collagen is therefore the best approach to fight against wrinkles.
Il n'en n'est pour s'en convaincre que de constater le nombre croissant deIt is only to be convinced of this that the growing number of
Dermatologues qui utilisent l'injection intradermique de collagène pour boucher les vides tissulaires responsables de rides. Cette méthode présente toutefois certains inconvénients plus ou moins importants. Outre le prix de ces interventions, le collagène injecté peut être reconnu comme faisant partie du non-soi et ainsi provoquer, a minima, des réactions inflammatoires forcément indésirables. De plus, ce matériel biologique surajouté artificiellement, subira rapidement la dégradation enzymatique normale, ce qui induira un cycle d'injections de collagène selon des fréquences de plus en plus rapprochées.Dermatologists who use the intradermal injection of collagen to fill the tissue voids responsible for wrinkles. This method however has certain more or less significant drawbacks. In addition to the price of these interventions, the Collagen injected can be recognized as part of non-self and thus cause, at a minimum, inflammatory reactions necessarily undesirable. In addition, this artificially added biological material will quickly undergo normal enzymatic degradation, which will induce a cycle of collagen injections according to increasingly closer frequencies.
L'invention faisant l'objet de cette demande de brevet réside dans le fait que nous avons mis au point un produit, le tripeptide, N-palmitoyl-Gly-His-Lys, qui permet de restaurer la concentration d'un collagène de meilleurs qualité, qui, étant néoformé par l'organisme lui-même, gommera ou réduira l'importance des rides tout en assurant une parfaite tolérance et indolore à l'usager. Ces effets ont été étudiés et démontrés, aussi bien m vitro qu' vivo, par des tests scientifiques sophistiqués qui seront explicités dans les exemples donnés dans cette demande de brevet. Cette séquence Gly-His-Lys, liée à un atome de cuivre, a été décrite en 1989 (WO 89/12441) dans des compositions cosmétiques destinées à épaissir le tissu adipeux sous-cutané des animaux à sang chaud et/ou la peau et ses sous-unités en général. Parmi d'autres séquences peptidiques, N-acylées on non, en 1990, nous avions décrit (FR90/13349) le Gly-His-Lys utilisable dans des préparations cosmétiques, sans toutefois en revendiquer d'activité physiologique particulière. Depuis le dépôt de notre brevet, certains documents ont revendiqués une activité cosmétique générale: en excluant la possibilité de N-acylation par un acide palmitique (FR-95 13543 dul 5/11/95),The invention which is the subject of this patent application resides in the fact that we have developed a product, the tripeptide, N-palmitoyl-Gly-His-Lys, which makes it possible to restore the concentration of a better collagen. quality, which, being new to the body itself, will erase or reduce the importance of wrinkles while ensuring perfect tolerance and painless to the user. These effects have been studied and demonstrated, both in vitro and in vivo, by sophisticated scientific tests which will be explained in the examples given in this patent application. This Gly-His-Lys sequence, linked to a copper atom, was described in 1989 (WO 89/12441) in cosmetic compositions intended to thicken the subcutaneous adipose tissue of warm-blooded animals and / or the skin and its sub-units in general. Among other peptide sequences, N-acylated or not, in 1990, we had described (FR90 / 13349) Gly-His-Lys usable in cosmetic preparations, without however claiming any particular physiological activity. Since the filing of our patent, certain documents have claimed general cosmetic activity: excluding the possibility of N-acylation by a palmitic acid (FR-95 13543 dul 5/11/95),
- en mentionnant qu'un tripeptide, non N-acylé, devant contenir toute association possible d'acides aminés se trouvant dans la thymuline ou dans la thymopoïétine AA (FR-95 13544) sans que la séquence Gly-His-Lys soit mentionnée, glycosylée et de préférence lié à un atome métallique comme le zinc,- by mentioning that a non-N-acylated tripeptide must contain any possible association of amino acids found in thymulin or in thymopoietin AA (FR-95 13544) without the Gly-His-Lys sequence being mentioned, glycosylated and preferably linked to a metal atom such as zinc,
- en ne décrivant que l'utilisation de la 3-méthyl-L-His, liée ou non à une autre molécule indéterminée pour faciliter le passage transcutané, en utilisation topique contre les altérations du collagène dues au rayonnements UV (WO- by only describing the use of 3-methyl-L-His, whether or not linked to another undetermined molecule to facilitate transcutaneous passage, in use topical against collagen damage due to UV radiation (WO
90/06102), - en ne mentionnant qu'un acide aminé dont l'histidine pouvant être greffé à une chaîne d'acide gras de 6 à 24 carbones, et revendiquant des activités 5 émulsifiante, antioxydante, bactéricide, chélatante ou comme filtre solaire (JP90/06102), - by mentioning only one amino acid including histidine which can be grafted to a fatty acid chain of 6 to 24 carbons, and claiming emulsifying, antioxidant, bactericidal, chelating or sunscreen activities (JP
2465.5/91). Enfin, ce qui n'était pas encore le cas en 1990, il est maintenant bien connu qu'il n'existe pas une seule sorte de collagène et que la qualité du tissu cutané dépend non seulement de la quantité du collagène tissulaire mais également de la o répartition harmonieuse de ses différentes formes. Les types I, H, II V et XI, formes fibrillaires, comblent les espaces vides alors que le type IV forme les réseau en feuillet de la lame basale et le type VU constitue les fibrilles d'ancrage des épithéliums squameux stratifiés (par exemple Albert B et al., Biologie Moléculaire de la cellule, 3 ae éd., Médecine Science, Flammarion éd., Paris, 1997:979-980). 5 De manière tout à fait surprenante, à la suite d'études approfondies, nous avons découvert que le tripeptide de séquence Gly-His-Lys, possédait une spectaculaire et imprévisible efficacité dans la réduction, voire la suppression, des rides mais également dans la prévention de leur apparition et ceci, quelle qu'en soit la cause: vieillissement, exposition prolongée et excessive au UV naturels ou artificiels, o hygiène de vie approximative2465.5 / 91). Finally, which was not yet the case in 1990, it is now well known that there is no single kind of collagen and that the quality of skin tissue depends not only on the quantity of tissue collagen but also on o the harmonious distribution of its different forms. Types I, H, II V and XI, fibrillar forms, fill the empty spaces while type IV forms the lamellar network of the basal lamina and type VU constitutes the anchor fibrils of the stratified squamous epithelia (for example Albert B et al, Molecular Biology of the cell, 3 ae ed, Science Medicine, ed Flammarion, Paris, 1997:... 979-980). 5 Surprisingly, following extensive studies, we discovered that the tripeptide of sequence Gly-His-Lys, had a spectacular and unpredictable effectiveness in reducing, even eliminating, wrinkles but also in prevention of their appearance and this, whatever the cause: aging, prolonged and excessive exposure to natural or artificial UV, o approximate lifestyle
Nous avons également constaté, comme il en est parfois le cas (FR 90 13349), que le fait d'acyler l'aminé N-terminale ou d'estérifier le groupe carboxyle de ce(s) peptide(s), augmente la stabilité de la molécule et la disponibilité tissulaire par facilitation du passage de la barrière lipidique cutanée de ce type de structure 5 essentiellement hydrophile.We have also found, as is sometimes the case (FR 90 13349), that acylating the N-terminal amine or esterifying the carboxyl group of this (these) peptide (s), increases the stability of the molecule and tissue availability by facilitating the passage of the skin lipid barrier of this type of essentially hydrophilic structure.
Dans ce cas, non seulement l'activité antiride est préservée mais elle est encore plus spectaculaire.In this case, not only is the anti-wrinkle activity preserved, but it is even more spectacular.
Les tripeptides, objets de cette demande de brevet, peuvent être obtenus soit par synthèse chimique classique (en phase hétérogène ou en phase homogène), soit par synthèse enzymatique (Kullman et al., J. Biol. Chem. 1980, 255, 8234) à partir des acides aminés constitutifs ou de leurs dérivés.The tripeptides which are the subject of this patent application can be obtained either by conventional chemical synthesis (in heterogeneous phase or in homogeneous phase), or by enzymatic synthesis (Kullman et al., J. Biol. Chem. 1980, 255, 8234) from the constituent amino acids or their derivatives.
La petite taille du tripeptide permet d'en faire la synthèse industrielle, à un coût avantageux. Sa grande activité démontrée en autorise l'utilisation commerciale dans un grand nombre de produits cosmétiques ou dermopharmaceutiques financièrement acceptables.The small size of the tripeptide allows it to be synthesized industrially, at an advantageous cost. Its large demonstrated activity authorizes commercial use in a large number of financially acceptable cosmetic or dermopharmaceutical products.
Le tripeptide, peut être obtenu également par fermentation d'une souche de bactéries, modifiées ou non par génie génétique, pour produire les séquences recherchées ou leurs différents fragments. Enfin, le tripeptide peut être obtenu par extraction de protéines d'origine animale ou végétale, préférentiellement végétale, susceptibles de contenir ces séquences au sein de leur structure, suivie d'une hydrolyse contrôlée, enzymatique ou non, qui libère le fragment peptidique de séquence Gly-His-Lys dans les plantes qui sont susceptibles de contenir ces séquences au sein de leur structure. L'hydrolyse ménagée permet de dégager ces fragments peptidiques.The tripeptide can also be obtained by fermentation of a strain of bacteria, modified or not by genetic engineering, to produce the desired sequences or their different fragments. Finally, the tripeptide can be obtained by extraction of proteins of animal or vegetable origin, preferably vegetable, capable of containing these sequences within their structure, followed by a controlled hydrolysis, enzymatic or not, which releases the peptide fragment of sequence Gly-His-Lys in plants which are likely to contain these sequences within their structure. The controlled hydrolysis makes it possible to release these peptide fragments.
Pour réaliser l'invention, il est possible, mais non nécessaire, d'extraire soit les protéines concernées d'abord et de les hydrolyser ensuite, soit d'effectuer l'hydrolyse d'abord sur un extrait brut et de purifier les fragments peptidiques ensuite. On peut également utiliser l'hydrolysât sans en extraire les fragments peptidiques en question, en s'assurant toutefois d'avoir arrêté la réaction enzymatique d'hydrolyse à temps et de doser la présence des peptides en question par des moyens analytiques appropriés (traçage par radioactivité, immunofluorescence ou immunoprécipitation avec des anticorps spécifiques, etc.). D'autres procédés plus simples ou plus complexes, conduisant à des produits moins chers ou plus purs sont facilement envisageables par l'homme de l'art connaissant le métier d'extraction et de purification des protéines et peptides. A titre d'exemple illustrant l'invention, on cite quelques formules cosmétiques représentatives mais non limitatives de l'invention: Exemple n° 1: Gel Carbopol 1342R 0,3 Propylène glycol 2,0To carry out the invention, it is possible, but not necessary, to extract either the proteins concerned first and then hydrolyze them, or to carry out the hydrolysis first on a crude extract and to purify the peptide fragments then. It is also possible to use the hydrolyzate without extracting the peptide fragments in question therefrom, making sure however to have stopped the enzymatic hydrolysis reaction in time and to measure the presence of the peptides in question by appropriate analytical means (tracing by radioactivity, immunofluorescence or immunoprecipitation with specific antibodies, etc.). Other simpler or more complex processes, leading to cheaper or purer products, are easily conceivable by those skilled in the art knowing the trade of extracting and purifying proteins and peptides. By way of example illustrating the invention, a few cosmetic formulas which are representative but not limiting of the invention are cited: Example No. 1: Carbopol 1342 R 0.3 gel Propylene glycol 2.0
Glycérine 1,0Glycerin 1.0
Vaseline blanche 1,5White petrolatum 1.5
Cylomethicone 6,0 Sipol C16C18S3 0,5Cylomethicone 6.0 Sipol C16C18S3 0.5
LubrajelR MS 10 triéthanolamine 0,3Lubrajel R MS 10 triethanolamine 0.3
N-Palmitoyl-Gly-His-Lys 0,0005N-Palmitoyl-Gly-His-Lys 0.0005
Eau, conservateurs, parfum qsp 100 g. Exemple n°2: CrèmeWater, preservatives, perfume qs 100 g. Example 2: Cream
BrijR 721 2.4Brij R 721 2.4
BrijR 72 2.6Brij R 72 2.6
ArlamolR E 8.0Arlamol R E 8.0
Cire d'abeille 0.5 AbilR ZP 2434 3.0Beeswax 0.5 Abil R ZP 2434 3.0
Propylène glycol 3.0Propylene glycol 3.0
CarbopolR 941 0.25Carbopol R 941 0.25
Triéthanolamine 0.250.25 triethanolamine
N-Palmitoyl-Gly-His-Lys 0,005 Eau, conservateurs, parfums qsp 100 gN-Palmitoyl-Gly-His-Lys 0.005 Water, preservatives, perfumes qs 100 g
Les activités décrites au début de cette demande sont illustrées par les exemples suivants.The activities described at the beginning of this request are illustrated by the following examples.
Exemple n° 3: Augmentation de la synthèse de collagène: in vitroExample No. 3: Increased collagen synthesis: in vitro
La méthode choisie est une variante de celle décrite par Augustin C. et al. (Skin Pharmacol. (1997);10:63-70) en ce que nous avons utilisé des explants de peau humaine au lieu de fibroblastes pulmonaires humains, ceci afin de rendre nos résultats directement exploitables en cosmétologie.The method chosen is a variant of that described by Augustin C. et al. (Skin Pharmacol. (1997); 10: 63-70) in that we used human skin explants instead of human pulmonary fibroblasts, in order to make our results directly usable in cosmetology.
Ces explants, provenant de plastie mammaire ou abdominale, sont incubés, pendant 72 heures en présence de 3H-proline, avec le tripeptide sous trois concentrations finales dans le milieu de culture ( 1.10"4 %, 3.10"4 % et 1.10"3 %; soit 1, 3 et 10 ppm). Les explants sont alors lavés, le derme et l'épiderme de chaque explant sont séparés, homogénéisés et lysés. La mesure de l'incorporation de 3H- proline est alors réalisée dans chaque lysat. Les essais sont faits en triplicate. Parallèlement des contrôles négatifs sont réalisés dans le mêmes conditions mais en l'absence du tripeptide. Des contrôles, positifs, quant à eux, sont réalisés en remplaçant le tripeptide testé par de la vitamine C.These explants, originating from mammary or abdominal plasty, are incubated, for 72 hours in the presence of 3 H-proline, with the tripeptide in three final concentrations in the culture medium (1.10 "4 %, 3.10 " 4 % and 1.10 "3 %; is 1, 3 and 10 ppm). The explants are then washed, the dermis and epidermis of each explant are separated, homogenized and lysed. The measurement of the incorporation of 3 H-proline is then carried out in each lysate. The tests are carried out in triplicate. At the same time, negative controls are carried out under the same conditions but in the absence of the tripeptide. Positive controls are made by replacing the tripeptide tested with vitamin C.
En présence de 1, 3 ou 10 ppm du tripeptide, l'incorporation de 3H-proline qui traduit la synthèse de collagène, est augmentée de respectivement 15,3 (± 1) %, 34,7 (± 4) % et 75,3 (± 4) % par rapport à ce qui est constaté dans les expériences témoins (sans le tripeptide).In the presence of 1, 3 or 10 ppm of the tripeptide, the incorporation of 3 H-proline which translates the synthesis of collagen, is increased by respectively 15.3 (± 1)%, 34.7 (± 4)% and 75 , 3 (± 4)% compared to what is observed in the control experiments (without the tripeptide).
Dans les mêmes conditions, le produit de référence, l'acide ascorbique, à la concentration de 0.5mM, augmente la synthèse du collagène de 32,7 (± 5) %. Des études complémentaire nous ont permis d'affiner ces résultats bruts et de constater que le collagène de type I, mais également les collagènes de types IV et VU augmentaient de façon telle que le collagène I néoformé pouvait combler des volumes dont les bords étaient constitués des collagènes de type IV et Vu, également néoformés, assurant ainsi à l'ensemble du tissu une nouvelle homogénéité et un effet durable sur la diminution ou la suppression des rides. Exemple n°4: Activité raffermissant cutané: in vitro Durant 24 heures, des fibroblates humains provenant de la même culture cellulaire, sont mis en présence de milieu de culture standard supplémenté, ou non pour les contrôles, avec différentes concentrations de tripeptide (1, 3 et 10 ppm). La stimulation de la synthèse de protéines est évaluée par colorimétrie (réaction dite du Biuret). Pour standardiser les résultats, la quantité de protéines mesurée est exprimée pourUnder the same conditions, the reference product, ascorbic acid, at a concentration of 0.5 mM, increases the synthesis of collagen by 32.7 (± 5)%. Complementary studies allowed us to refine these raw results and to note that collagen type I, but also collagens type IV and VU increased in such a way that collagen I neoformé could fill volumes whose edges consisted of type IV and Vu collagens, also new, thus ensuring a new homogeneity for the entire tissue and a lasting effect on the reduction or elimination of wrinkles. Example No. 4: Skin Firming Activity: In Vitro For 24 hours, human fibroblates originating from the same cell culture are placed in the presence of standard culture medium supplemented, or not for the controls, with different concentrations of tripeptide (1, 3 and 10 ppm). The stimulation of protein synthesis is evaluated by colorimetry (so-called Biuret reaction). To standardize the results, the quantity of protein measured is expressed for
1000 cellules présentes dans le test. Par rapport aux expérimentations contrôles, en présence soit de 1, 3 et 10 ppm de tripeptide, l'augmentation de la concentration de protéines est respectivement de 15,3 (± 1)%, 32,2 (±3)% et 53,5 (± 3)%. Ainsi, cet essai in vitro démontre le potentiel stimulant, concentration dépendant, au niveau cutané du tripeptide, effet directement lié à un raffermissement et à un épaississement des peaux trop fines. Exemple n° 5: Activité antirides: in vivo1000 cells present in the test. Compared to control experiments, in the presence of 1, 3 and 10 ppm of tripeptide, the increase in the protein concentration is respectively 15.3 (± 1)%, 32.2 (± 3)% and 53, 5 (± 3)%. Thus, this in vitro test demonstrates the stimulating potential, dependent concentration, at the level skin of the tripeptide, effect directly linked to a firming and thickening of excessively thin skin. Example 5: Anti-wrinkle activity: in vivo
Cet exemple rapporte l'effet antirides obtenu, in vivo, sur un panel constitué de 150 volontaires adultes de sexe fémimn, âgées de 35 à 63 ans. Le pouvoir antirides de la crème de l'exemple n°2, contenant le N-Palmitoyl-Gly-His-Lys, à la concentration de 0,005 % (soit 50 ppm), est comparé à celui d'une crème placebo (même crème mais sans l'actif). Les crèmes sont appliquées sur des sites précisément identifiés, situés sur le coin de l'œil droit ou gauche, selon une répartition randomisée, deux fois par jour, pendant 28 jours. Cette expérience a été réalisée selon un protocole dit en double aveugle puisque ni le volontaire, ni les expérimentateurs ne connaissaient la nature du produit appliqué. Ce n'est qu'au moment de l'analyse de tous les résultats que la levée des codes a été pratiquée. Le paramètre pris en compte est le relief cutané, au niveau du contour de l'œil (rides dites de la patte d'oie). Les quantifications des différentes variables du relief sont réalisées par analyse vidéo-informatique d'empreintes au silicone prises à la surface de la peau selon les protocoles décrits par Corcuff et al. (1985, Int. J. Cosm. Sci.l→.l 17-126) et Corcuff et al. (1995, in Handbook ofnon-invasive methods and the skin, Serup & Jemec eds., CRC Press: 89-96). Les tableaux ci-dessous indiquent la différence, en pourcentage, des valeurs moyennes obtenues entre T +28 ou T + 60 jours et T0 pour les profondeurs moyennes de la ride principale (colonne A) ou pour l'ensemble des plis (col. B); pour la densité des plis principaux (col. C) ainsi que pour la mesure de la rugosité (col. D). Après 28 Jours de traitementThis example reports the anti-wrinkle effect obtained, in vivo, on a panel made up of 150 adult female volunteers, aged 35 to 63 years. The anti-wrinkle power of the cream of Example 2, containing N-Palmitoyl-Gly-His-Lys, at a concentration of 0.005% (i.e. 50 ppm), is compared to that of a placebo cream (same cream but without the asset). The creams are applied to precisely identified sites, located on the corner of the right or left eye, according to a randomized distribution, twice a day, for 28 days. This experiment was carried out according to a so-called double-blind protocol since neither the volunteer nor the experimenters knew the nature of the product applied. It was only when all the results were analyzed that the codes were lifted. The parameter taken into account is the skin relief, at the level of the eye contour (so-called crow's feet wrinkles). The quantifications of the different relief variables are carried out by computer-video analysis of silicone impressions taken on the surface of the skin according to the protocols described by Corcuff et al. (1985, Int. J. Cosm. Sci.l → .l 17-126) and Corcuff et al. (1995, in Handbook ofnon-invasive methods and the skin, Serup & Jemec eds., CRC Press: 89-96). The tables below indicate the difference, in percentage, of the average values obtained between T +28 or T + 60 days and T0 for the average depths of the main wrinkle (column A) or for all the folds (col. B ); for the density of the main folds (col. C) as well as for the measurement of roughness (col. D). After 28 Days of Processing
A B C DA B C D
Placebo 0,2 + 0,2 - 0,7 + 1,0Placebo 0.2 + 0.2 - 0.7 + 1.0
Tripeptide - 15,7 - 17,8 - 29,7 - 27,3 Après 60 Jours de traitementTripeptide - 15.7 - 17.8 - 29.7 - 27.3 After 60 Days of Processing
A B C DA B C D
Placebo 0,3 + 0,2 - 0,9 + 1,2Placebo 0.3 + 0.2 - 0.9 + 1.2
Tripeptide - 25,3 - 28,9 - 41,3 - 34,4 II est à noter que, dans les mêmes conditions expérimentales, la crème placebo ne présente absolument aucun effet si le N-Palmitoyl-Gly-His-Lys n'y a pas été incorporé, ce qui démontre bien que c'est seulement au N-Palmitoyl-Gly-His-Lys que l'on peut attribuer l'effet bénéfique observé.Tripeptide - 25.3 - 28.9 - 41.3 - 34.4 It should be noted that, under the same experimental conditions, the placebo cream has absolutely no effect if N-Palmitoyl-Gly-His-Lys does not was not incorporated into it, which clearly shows that it is only to N-Palmitoyl-Gly-His-Lys that the beneficial effect observed can be attributed.
La crème contenant le N-Palmitoyl-Gly-His-Lys précédemment décrit démontre donc clairement un puissant effet antirides puisque l'on observe une différence progressive importante entre le début et la fin de l'étude in vivo et ceci, sur l'ensemble des quatre paramètres classiquement utilisés dans cette indication.The cream containing the N-Palmitoyl-Gly-His-Lys previously described therefore clearly demonstrates a powerful anti-wrinkle effect since there is a significant progressive difference between the start and the end of the in vivo study and this, on the whole of the four parameters conventionally used in this indication.
Le résultat le plus remarquable que nous ayons constaté à la fin de cette étude réalisée sur 150 volontaires a été l'appréciation personnelle spontanée des volontaires. En effet, au moment de chaque mesure (T+28 et T+60 jours), parmi d'autres questions sur la tolérance et le confort cosmétique des crèmes testées, chaque volontaire devait indiquer quel était le côté qui lui semblait le meilleur.The most remarkable result we saw at the end of this study carried out on 150 volunteers was the spontaneous personal appreciation of the volunteers. Indeed, at the time of each measurement (T + 28 and T + 60 days), among other questions on the tolerance and cosmetic comfort of the creams tested, each volunteer had to indicate which side seemed to him the best.
Le dépouillement final des résultats, a démontré qu'à T+28 jours et à T +60 jours, respectivement 78 % et 82% des volontaires avaient désigné le côté recevant la crème avec le tripeptide.The final analysis of the results demonstrated that at T + 28 days and T +60 days, respectively 78% and 82% of the volunteers had designated the side receiving the cream with the tripeptide.
Le protocole réalisé en double aveugle démontre encore plus l'effet spectaculaire du tripeptide N-Palmitoyl-Gly-His-Lys.The double-blind protocol further demonstrates the spectacular effect of the N-Palmitoyl-Gly-His-Lys tripeptide.
Exemple n° 6: Activité sur le galbe de la bouche: in vivoExample 6: Activity on the curve of the mouth: in vivo
L'étude a évalué chez 10 volontaires de sexe fémimn (âgées de 18 et 45 ans) présentant des lèvres fines et sèches, l'effet d'un "stick" labial sur l'hydratation superficielle, le lissage et le volume des lèvres.The study evaluated in 10 female volunteers (aged 18 and 45) with thin and dry lips, the effect of a labial "stick" on the surface hydration, smoothing and volume of the lips.
Ce stick était de composition classique si ce n'est l'ajout de notre N-Palmitoyl-Gly-This stick was of classic composition if it is not the addition of our N-Palmitoyl-Gly-
His-Lys à la concentration de 10 ppm.His-Lys at a concentration of 10 ppm.
Le niveau d'hydratation superficielle a été côté par le dermatologue en charge de l'étude; le volume mesuré par Toposkin® (à partir de deux photos prises simultanément sous deux angles différents, un logiciel adapté permet de restituer l'image en trois dimensions et de faire des mesures volumétriques). Par ailleurs, les volontaires avaient à remplir un questionnaires sur des critères subjectifs. Le tableau suivant montre les moyennes (unités arbitraires) et les écart types obtenus à TO et T +30 jours sur l'hydratation évaluée au niveau de la lèvre supérieure et de la lèvre inférieure et sur le volume labial flobal.The level of surface hydration was rated by the dermatologist in charge of the study; the volume measured by Toposkin ® (from two photos taken simultaneously from two different angles, an adapted software allows to restore the image in three dimensions and to make volumetric measurements). In addition, the volunteers had to fill out questionnaires based on subjective criteria. The following table shows the means (arbitrary units) and the standard deviations obtained at TO and T +30 days on the hydration evaluated at the level of the upper lip and the lower lip and on the labial flobal volume.
Hydratation de la lèvre Volume supérieure inférieure T O 2,0 + 07 1,7 + 0,7 '3,7 ± l",0Lip hydration Lower upper volume TO 2.0 + 07 1.7 + 0.7 ' 3.7 ± l " , 0
T +30 3^ ±0,6 2 + + 0,5 4,9 ± 1,5T +30 3 ^ ± 0.6 2 + + 0.5 4.9 ± 1.5
L'auto-évaluation a montré que une amélioration évidente de l'état des lèvres (chez 100 % des volontaires), une satisfaction sur le confort cutané (70 %), une sensation de protection (70 %), une amélioration de la rugosité (70 %) et une amélioration de la desquamation jugée comme modérée (40 %) à grande (20 %).The self-assessment showed that an obvious improvement in the state of the lips (in 100% of volunteers), satisfaction with skin comfort (70%), a feeling of protection (70%), an improvement in roughness. (70%) and an improvement in scaling judged as moderate (40%) to large (20%).
Cette étude démontre clairement l'effet bénéfique du stick labial contenant notre N- Palmitoyl-Gly-His-Lys, à une concentration aussi basse que 10 ppm), sur des paramètres subjectifs et objectifs qualifiant l'aspect et l'état physiologique des lèvres. Par greffage d'une chaîne d'acide gras, de 2 à 22 carbones, hydroxylée ou non, saturée ou non, linéaire ou ramifiée, sulfatée ou non, sur l'aminé N-terminale du tripeptide Gly-His-Lys pour obtenir le N-Palmitoyl-Gly-His-Lys, il est avantageux de conférer à ces peptides, hydrophiles par nature, des propriétés lipophiles pour augmenter leur passage cutané et donc leur disponibilité et de faciliter leur incorporation dans les compositions cosmétiques et dermopharmaceutiques.This study clearly demonstrates the beneficial effect of the lip stick containing our N-Palmitoyl-Gly-His-Lys, at a concentration as low as 10 ppm), on subjective and objective parameters qualifying the appearance and physiological state of the lips. . By grafting a fatty acid chain, from 2 to 22 carbons, hydroxylated or not, saturated or not, linear or branched, sulfated or not, on the N-terminal amine of the Gly-His-Lys tripeptide to obtain the N-Palmitoyl-Gly-His-Lys, it is advantageous to confer on these peptides, hydrophilic by nature, lipophilic properties to increase their cutaneous passage and therefore their availability and to facilitate their incorporation in cosmetic and dermopharmaceutical compositions.
Le tripeptide de ce brevet, acylé ou non, peut être obtenu par synthèse chimique, par voie enzymatique, par fermentation, par extraction de protéines d'origine végétale, par synthèse peptidique classique en phase homogène ou hétérogène ou par synthèse enzymatique à partir des acides aminés constitutifs. Le tripeptide de ce brevet, acylé ou non, objet de ce brevet, peut être obtenu par extraction de protéines de plantes, suivie d'hydrolyse, enzymatique ou non enzymatique, de façon à générer des fragments peptidiques de taille moyenne comprise entre 300 et 1500 daltons, une partie des fragments libérés devant contenir la séquence Gly-His-Lys.The tripeptide of this patent, acylated or not, can be obtained by chemical synthesis, by enzymatic way, by fermentation, by extraction of proteins of vegetable origin, by classic peptide synthesis in homogeneous or heterogeneous phase or by enzymatic synthesis starting from acids constituent amines. The tripeptide of this patent, acylated or not, subject of this patent, can be obtained by extraction of plant proteins, followed by hydrolysis, enzymatic or non-enzymatic, so as to generate peptide fragments of average size between 300 and 1500 daltons, part of the released fragments must contain the Gly-His-Lys sequence.
Le tripeptide de ce brevet, acylé ou non, peut être utilisé à des concentrations variant entre 0,1 et 1000 ppm (p/p), préférentiellement entre 1 et 200 ppm (p/p) dans le produit cosmétique ou dermopharmaceutique fini. Le tripeptide de ce brevet, acylé ou non, peut être utilisé sous forme de solution, de dispersion, d'émulsion, ou encapsulé dans des vecteurs comme les macro-, micro- ou nanocapsules, des liposomes ou des chylomicrons, ou inclus dans des macro-, micro- ou nanoparticules, ou dans des microéponges, ou adsorbé sur des polymères organiques poudreux, les talcs, bentonites et autres supports minéraux. Le tripeptide de ce brevet, acylé ou non, peut être utilisé dans toute forme galénique: émulsions H/E et E/H, laits, lotions, polymères gélifiants et viscosants, tensioactifs et émulsifiants, pommades, lotions capillaires, shampooings, savons, poudres, sticks et crayons, sprays, huiles corporelles.The tripeptide of this patent, acylated or not, can be used at concentrations varying between 0.1 and 1000 ppm (w / w), preferably between 1 and 200 ppm (w / w) in the finished cosmetic or dermopharmaceutical product. The tripeptide of this patent, acylated or not, can be used in the form of a solution, dispersion, emulsion, or encapsulated in vectors such as macro-, micro- or nanocapsules, liposomes or chylomicrons, or included in macro-, micro- or nanoparticles, or in micro-sponges, or adsorbed on powdery organic polymers, talcs, bentonites and other mineral supports. The tripeptide of this patent, acylated or not, can be used in any galenical form: O / W and W / O emulsions, milks, lotions, gelling and viscosifying polymers, surfactants and emulsifiers, ointments, hair lotions, shampoos, soaps, powders , sticks and pencils, sprays, body oils.
Le tripeptide de ce brevet, acylé ou non, peut être utilisé avec tout autre ingrédient habituellement utilisé: lipides d'extraction et/ou de synthèse, polymères gélifiants et viscosants, tensioactifs et émulsifiants, principes actifs hydro- ou liposolubles, extraits végétaux, extraits tissulaires, extraits marins, filtres solaires, antioxydants. Le tripeptide de ce brevet, acylé ou non, peut être utilisé dans les applications cosmétiques pour éliminer, réduire ou prévenir l'apparition de rides, qu'elles qu'en soient la localisation et la cause. Le tripeptide de ce brevet, acylé ou non, peut être utilisé pour la préparation d'un médicament pour éliminer, réduire ou prévenir l'apparition de rides, qu'elles qu'en soient la localisation et la cause. The tripeptide of this patent, acylated or not, can be used with any other ingredient usually used: extraction and / or synthetic lipids, gelling and viscosifying polymers, surfactants and emulsifiers, water or liposoluble active principles, plant extracts, extracts tissues, marine extracts, sun filters, antioxidants. The tripeptide of this patent, acylated or not, can be used in cosmetic applications to eliminate, reduce or prevent the appearance of wrinkles, whatever their location and cause. The tripeptide of this patent, acylated or not, can be used for the preparation of a medicament for eliminating, reducing or preventing the appearance of wrinkles, whatever their location and cause.

Claims

Revendications claims
1. Utilisation du tripeptide Gly-His-Lys dans des compositions cosmétiques ou dermopharmaceutiques pour raffermir le tissu cutané ainsi que pour améliorer1. Use of the tripeptide Gly-His-Lys in cosmetic or dermopharmaceutical compositions for firming the skin tissue as well as for improving
5 le galbe de la bouche.5 the curve of the mouth.
2. Utilisation du tripeptide dans des compositions cosmétiques ou dermopharmaceutiques selon 1 caractérisé en ce que sa lipophilie est augmentée par greffage d'une chaîne d'acide gras, de 2 à 22 carbones, hydroxylée ou non, saturée ou non, linéaire ou ramifiée, sulfatée ou non, sur 0 l'aminé N-terminale et/ou par l'estérification de son groupe carboxyle.2. Use of the tripeptide in cosmetic or dermopharmaceutical compositions according to 1, characterized in that its lipophilicity is increased by grafting a fatty acid chain, from 2 to 22 carbons, hydroxylated or not, saturated or not, linear or branched, sulfated or not, on the N-terminal amine and / or by the esterification of its carboxyl group.
3. Compositions cosmétiques caractérisées en ce qu'elles contiennent au moins un des tripeptides selon 1 à 2.3. Cosmetic compositions characterized in that they contain at least one of the tripeptides according to 1 to 2.
4. Compositions cosmétiques ou dermopharmaceutiques selon 3, caractérisées en ce que le ou les tripeptide(s) est/sont obtenu(s) par synthèse chimique, par voie 5 enzymatique, par fermentation ou par extraction de protéines d'origine végétale.4. Cosmetic or dermopharmaceutical compositions according to 3, characterized in that the tripeptide (s) is / are obtained by chemical synthesis, by enzymatic route, by fermentation or by extraction of proteins of vegetable origin.
5. Compositions cosmétiques ou dermopharmaceutiques selon 3 à 4, caractérisées en ce que le ou les tripeptide(s) est/sont obtenu(s) par synthèse peptidique classique en phase homogène ou hétérogène ou par synthèse o enzymatique à partir des acides aminés constitutifs.5. Cosmetic or dermopharmaceutical compositions according to 3 to 4, characterized in that the tripeptide (s) is / are obtained by conventional peptide synthesis in homogeneous or heterogeneous phase or by o enzymatic synthesis from the constituent amino acids.
6. Compositions cosmétiques ou dermopharmaceutiques selon 3 à 5, caractérisées en ce que le ou les tripeptide(s) est/sont obtenu(s) par extraction de protéines de plantes, suivie d'hydrolyse, enzymatique ou non enzymatique, de façon à générer des fragments peptidiques de taille moyenne comprise entre 5 300 et 1500 daltons, une partie des fragments libérés devant contenir la séquence Gly-His-Lys.6. Cosmetic or dermopharmaceutical compositions according to 3 to 5, characterized in that the tripeptide (s) is / are obtained by extraction of plant proteins, followed by hydrolysis, enzymatic or non-enzymatic, so as to generate peptide fragments of average size between 5,300 and 1,500 daltons, part of the fragments released must contain the sequence Gly-His-Lys.
7. Compositions cosmétiques ou dermopharmaceutiques selon 3 à 6 caractérisées en ce que le ou les tripeptide(s) est/sont utilisé(s) à des concentrations variant entre 0,1 et 1000 ppm (p/p), préférentiellement entre 1 et 200 ppm (p/p) dans 0 le produit fini. 7. Cosmetic or dermopharmaceutical compositions according to 3 to 6, characterized in that the tripeptide (s) is / are used at concentrations varying between 0.1 and 1000 ppm (w / w), preferably between 1 and 200 ppm (w / w) in 0 the finished product.
8. Compositions cosmétiques ou dermopharmaceutiques selon 3 à 7 caractérisées en ce que le ou les tripeptide(s) est/sont utilisé(s) sous forme de solution, de dispersion, d'émulsion, ou encapsulé dans des vecteurs comme les macro-, micro- ou nanocapsules, des liposomes ou des chylomicrons, ou inclus dans des macro-, micro- ou nanoparticules, ou dans des microéponges, ou adsorbé sur des polymères organiques poudreux, les talcs, bentonites et autres supports minéraux.8. Cosmetic or dermopharmaceutical compositions according to 3 to 7, characterized in that the tripeptide (s) is / are used in the form of a solution, dispersion, emulsion, or encapsulated in vectors such as macro-, micro- or nanocapsules, liposomes or chylomicrons, or included in macro-, micro- or nanoparticles, or in micro-sponges, or adsorbed on powdery organic polymers, talcs, bentonites and other mineral supports.
9. Compositions cosmétiques ou dermopharmaceutiques selon 3 à 8 caractérisées en ce que le ou les tripeptide(s) est/sont utilisé(s) dans toute forme galénique: émulsions H/E et E/H, laits, lotions, polymères gélifiants et viscosants, tensioactifs et émulsifiants, pommades, lotions capillaires, shampooings, savons, poudres, sticks et crayons, sprays, huiles corporelles.9. Cosmetic or dermopharmaceutical compositions according to 3 to 8, characterized in that the tripeptide (s) is / are used in any galenical form: O / W and W / O emulsions, milks, lotions, gelling and viscosifying polymers , surfactants and emulsifiers, ointments, hair lotions, shampoos, soaps, powders, sticks and pencils, sprays, body oils.
10. Compositions cosmétiques ou dermopharmaceutiques selon 3 à 9 caractérisées en ce que le tripeptide est utilisé avec tout autre ingrédient habituellement utilisé: lipides d'extraction et/ou de synthèse, polymères gélifiants et viscosants, tensioactifs et émulsifiants, principes actifs hydro- ou liposolubles, extraits végétaux, extraits tissulaires, extraits marins, filtres solaires, antioxydants.10. Cosmetic or dermopharmaceutical compositions according to 3 to 9, characterized in that the tripeptide is used with any other ingredient usually used: extraction and / or synthetic lipids, gelling and viscosifying polymers, surfactants and emulsifiers, water-soluble or liposoluble active principles , plant extracts, tissue extracts, marine extracts, sun filters, antioxidants.
11. Compositions cosmétiques ou dermopharmaceutiques selon 3 à 10 utilisées pour la préparation d'un médicament pour raffermir le tissu cutané ainsi que pour améliorer le galbe de la bouche. 11. Cosmetic or dermopharmaceutical compositions according to 3 to 10 used for the preparation of a medicament for firming the skin tissue as well as for improving the shape of the mouth.
PCT/FR2000/003236 1999-12-17 2000-11-21 Cosmetic or dermopharmaceutical compositions containing the n-palmytoyl-gly-hys-lys tripeptide WO2001043701A2 (en)

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EP1634576A1 (en) * 2004-08-13 2006-03-15 Henkel Kommanditgesellschaft auf Aktien DNA repair enzymes and oligopeptides containing cosmetic and dermatological compositions
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KR101045658B1 (en) * 2003-11-17 2011-07-01 쎄데르마 Compositions Comprising Tetrapeptide and Tripeptide Mixtures
US6974799B2 (en) 2003-11-17 2005-12-13 Sederma S.A.S. Compositions containing mixtures of tetrapeptides and tripeptides
WO2005048968A1 (en) * 2003-11-17 2005-06-02 Sederma Compositions containing mixtures of tetrapeptides and tripeptides
EP1634576A1 (en) * 2004-08-13 2006-03-15 Henkel Kommanditgesellschaft auf Aktien DNA repair enzymes and oligopeptides containing cosmetic and dermatological compositions
WO2006053688A1 (en) * 2004-11-17 2006-05-26 Henkel Kommanditgesellschaft Auf Aktien Cosmetic and dermatological preparations for the treatment of mature skin
US8846019B2 (en) 2005-09-06 2014-09-30 Sederma Use of protoberberines as an active substance regulating the pilosebaceous unit
WO2007087738A1 (en) * 2006-02-03 2007-08-09 Pentapharm Ag Biologically active tripeptides and copper complexes and salts thereof
US8404648B2 (en) 2006-02-16 2013-03-26 Sederma Polypeptides KXK and their use
US8507649B2 (en) 2006-05-05 2013-08-13 Sederma Cosmetic compositions comprising at least one peptide with at least one immobilized aromatic cycle
EP2510982A1 (en) 2006-05-05 2012-10-17 Sederma Cosmetic compositions comprising at least one peptide with at least one immobilized aromatic cycle
JP2010528090A (en) * 2007-05-29 2010-08-19 シャネル パフュームズ ビューテ Cosmetic composition comprising an active agent capable of stimulating tensin 1 expression
WO2010067327A1 (en) 2008-12-11 2010-06-17 Sederma Cosmetic composition containing acetylated oligoglucuronans
EP3744729A1 (en) 2009-01-16 2020-12-02 Sederma Compounds, in particular peptides, compositions comprising them and cosmetic and dermopharmaceutical uses
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WO2010082176A2 (en) 2009-01-16 2010-07-22 Sederma Cosmetic composition containing kxk type peptides and uses
WO2010082175A2 (en) 2009-01-16 2010-07-22 Sederma New compounds, in particular peptides, compositions comprising them and cosmetic and dermopharmaceutical uses
US9050477B2 (en) 2009-04-17 2015-06-09 Sederma Cosmetic compositions comprising oridonin and new cosmetic uses
WO2010122423A2 (en) 2009-04-22 2010-10-28 Dsm Ip Assets B.V. Novel composition
WO2010136965A2 (en) 2009-05-26 2010-12-02 Sederma Cosmetic use of tyr-arg dipeptide to combat cutaneous sa
WO2011086532A1 (en) 2010-01-18 2011-07-21 Sederma New lipo-phosphated or lipo-sulphated compound, compositions comprising it and topical uses thereof
WO2011125040A2 (en) 2010-04-08 2011-10-13 Sederma New polyterpene type compounds, compositions containing them and topical uses thereof
US9126060B2 (en) 2010-04-08 2015-09-08 Sederma Cosmetic use of geranylgeranyl-2-propanol
WO2011125039A2 (en) 2010-04-08 2011-10-13 Sederma Cosmetic use of geranylgeranyl-2-propanol
WO2014161863A1 (en) 2013-04-03 2014-10-09 Irbm Science Park S.P.A. Dermatological and/or cosmetic peptides for use in skin treatment
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CN108218956A (en) * 2018-02-23 2018-06-29 广州同隽医药科技有限公司 A kind of liquid-phase synthesis process of palmityl tripeptides -1
WO2021170754A1 (en) 2020-02-28 2021-09-02 Sederma Recombinant microalgae able to produce kttks peptides, polypeptides, or proteins and their derivatives and associated method and uses thereof
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WO2022051831A1 (en) * 2020-09-11 2022-03-17 Chemyunion Ltda. Composition, use of the composition, cosmetic method and method for modulating the production of sebum

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