EP0618801A1 - Cosmetic or pharmaceutical composition containing a black horehound extract - Google Patents

Cosmetic or pharmaceutical composition containing a black horehound extract

Info

Publication number
EP0618801A1
EP0618801A1 EP93901780A EP93901780A EP0618801A1 EP 0618801 A1 EP0618801 A1 EP 0618801A1 EP 93901780 A EP93901780 A EP 93901780A EP 93901780 A EP93901780 A EP 93901780A EP 0618801 A1 EP0618801 A1 EP 0618801A1
Authority
EP
European Patent Office
Prior art keywords
extract
skin
pigmentation
composition
cosmetic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP93901780A
Other languages
German (de)
French (fr)
Inventor
Frédéric Bonte
Alain Les Poissons Meybeck
Marc Dumas
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LVMH Recherche GIE
Original Assignee
LVMH Recherche GIE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by LVMH Recherche GIE filed Critical LVMH Recherche GIE
Publication of EP0618801A1 publication Critical patent/EP0618801A1/en
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61Q19/06—Preparations for care of the skin for countering cellulitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61Q19/04—Preparations for care of the skin for chemically tanning the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/06—Preparations for styling the hair, e.g. by temporary shaping or colouring
    • A61Q5/065—Preparations for temporary colouring the hair, e.g. direct dyes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/10—Preparations for permanently dyeing the hair

Definitions

  • the present invention essentially relates to a cosmetic or pharmaceutical composition, in particular a dermatological composition, containing an extract of bundle, intended in particular for promoting pigmentation of the skin or hair, or for reducing the amount of triglycerides in adipocytes and its manufacturing process.
  • the present invention also relates to the use of a bundle extract for the preparation of such a cosmetic or pharmaceutical composition, in particular intended for treating pigmentation disorders or for reducing the amount of triglycerides in adipocytes.
  • Plants of the genus ballote are part of the family of labiates, from temperate regions.
  • the present invention is based on the discovery that the bundle extracts, originating from the whole plant, and in particular from the aerial parts and in particular from the stems and leaves, have interesting biological properties which can be used in the cosmetic and pharmaceutical fields. It has in particular been observed by the inventors that these extracts unexpectedly possess a stimulating activity of melanogenesis, at the level of the melanocytes present in the skin or the hair follicles, in particular those of the scalp, and thus make it possible to favor the pigmentation of the skin or the hair, as well as carry out a treatment of the pigmentation disorders of the skin and the hair by more particularly promoting the bio ⁇ synthesis of melanin. Very good results in this area have been obtained with extracts from the whole plant, and in particular from the aerial parts and in particular from the stems and leaves of bundles.
  • extracts of bundle unexpectedly possess an activity reducing the amount of triglycerides in adipocytes, in particular by inhibiting their synthesis in these cells.
  • These extracts thus make it possible to avoid the development of fatty accumulations in the organism, such as cellu ⁇ lite, and are thus particularly useful for preparing cosmetic or pharmaceutical compositions, in particular dermatological, slimming preparations.
  • the present invention therefore aims to solve the new technical problem consisting in the supply of a new cosmetic or pharmaceutical composition, especially dermatological, intended in particular to promote pigmentation of the skin, to prevent or slow the appearance of white hair. .
  • Another object of the present invention is to solve the new technical problem consisting in the preparation of a new formulation of a cosmetic or pharmaceutical composition having a good activity for stimulating melanogenesis in the melanocytes present in the skin or in the follicles. hair, especially those of the scalp.
  • the present invention also aims to provide a solution to the new technical problem consisting in the supply of a plant extract which is particularly easy to obtain, which in itself exhibits a good stimulating activity of melanogenesis, at the level of melanocytes. present in the skin or hair follicles, without having to perform the isolation of any active substance, these isolation procedures are generally long and expensive.
  • the present invention also aims to solve the new technical problem consisting in the preparation of a new formulation of a cosmetic or pharmaceutical composition having a good activity reducing the amount of t ⁇ ' glycerides in adipocytes, thus allowing d 'avoid the development of fatty accumulations in the body, such as cellulite.
  • the present invention also aims to provide a solution to the new technical problem consisting in the supply of a plant extract which is particularly easy to obtain, which itself exhibits a good activity reducing the amount of trigly ⁇ cerides in the adipocytes. , without having to carry out the isolation of any active substance, these isolation methods being generally long and costly. All these new technical problems are solved for
  • the first time by the present invention in a satisfactory manner, usable on an industrial scale.
  • the present invention relates to a cosmetic or pharmaceutical composition, in particular a dermatological composition, intended in particular to promote pigmentation of the skin, to prevent or slow down the appearance of white hair; reduce the amount of triglycerides in adipocytes, avoid the development of fatty accumulation in the body, such as cellulite, characterized in that it comprises, as active ingredient, a cosmetically or pharmaceutically effective amount a bundle extract, optionally in a cosmetically or pharmaceutically acceptable excipient.
  • cosmetic or pharmaceutically effective amount means an amount at least equal to the minimum amount which is necessary to observe a significant effect, respectively cosmetic or pharmaceutical.
  • the ballote extract is chosen from extracts of Ballota nigra, Ballota lanata and Ballota suavelens.
  • the bale extract is chosen from an extract of the whole plant, and an extract from the aerial parts, in particular essen ⁇ tially from the stems and leaves.
  • the above-mentioned bundle extract is an extract advantageously obtained by a process comprising at least one extraction step with, for example, a solvent chosen from the group consisting of water,
  • a solvent chosen from the group consisting of water
  • the alcohols preferably comprising 1 to 4 carbon atoms such as methanol, ethanol or propanol, a hydroalcoholic mixture of these alcohols, chlorinated solvents containing 1 or 2 carbon atoms such as chloroform or dichloromethane, organic esters comprising preferably 3 to 6 carbon atoms such as ethyl acetate.
  • organic solvents such as aromatic hydrocarbons, in particular benzene, toluene or xylene, aliphatic or halogenated aromatic hydrocarbons, dialkyl ethers, dialkyl ketones, alkanols, carboxylic acids and their esters or other solvents, such as dimethylformamide.
  • Dioxane Tetrahydrofuran and dimethyl sulfoxide, or even supercritical carbon dioxide.
  • the ratio of the plant material to the extractant can be chosen from a wide range, however it is generally between 1: 5 and 1:20 parts by weight, and it is preferably approximately 1:10.
  • the extraction is carried out at temperatures between ambient temperature and the boiling point of the solvent used for the extraction.
  • An interesting extraction technique is the so-called Soxhlet extraction technique.
  • the phase containing the extract is filtered, then concentrated and / or evaporated to dryness under reduced pressure or by lyophilization.
  • the concentration of the extracts used in accordance with the present invention, for the preparation of a cosmetic or pharmaceutical composition expressed in dry weight is between 0.0001% and 5% by weight, preferably between 0, 01% and 0.5% by weight, relative to the total weight of the composition.
  • the cosmetic or pharmaceutical, in particular dermatological, compositions according to the present invention can be prepared in forms suitable for various modes of administration. In particular, they can be in a form intended for super administration here on the skin or the scalp, such as a cream, a gel, a milk or a lotion, in order to promote the pigmentation of the skin, prevent or slow the appearance of gray hair.
  • the cosmetic or pharmaceutical, in particular dermatological, compositions according to the invention find various applications in cosmetology or in pharmacy in particular in dermato ⁇ logy, in particular When the restoration of normal pigmentation or its increase is sought.
  • compositions can be used as sunscreen products to accelerate or intensify tanning, which, in addition to the aesthetic advantage often sought after, makes it possible to strengthen the natural defenses against ultraviolet radiation by increasing the level of melanin in the epidermis.
  • These compositions can also be used, for example in the form of creams, to give the skin a more tanned appearance, or alternatively, in the form of lotions, for preventing or slowing the appearance of white hair.
  • the compositions according to the present invention can be used as therapeutic agents, alone or in combination with other drugs, in particular in topical administration in the treatment of dysfunctions of melanocytes.
  • the extracts according to the invention make it possible to promote the differentiation of melanocytes, that is to say say to favor the obtaining of more mature or better differentiated melanosomes in cultures of human melanocytes.
  • a particularly interesting application resides in an application of these extracts according to the invention in a method of treatment of melanocytes in culture, in particular of normal human melanocytes in culture, with a view to making them acquire maturation characters suitable for their ultimate use. better.
  • the subsequent use can consist of melanocyte transplants in humans, in particular for treating certain pigmentation disorders, such as vitiligo.
  • the invention also include various applie -ions in cosmetology or pharmacy notamme * dermatology r.otamment topical administration, for drafted: The amount of triglycerides in the fat cells. It is known in particular that The synthesis of triglycerides by adipocytes goes hand in hand with the development of fatty accumulations in the organism, such as celLulite.
  • the extracts according to the invention find a particularly advantageous application in cosmetic or pharmaceutical, in particular dermatological, slimming compositions, with a view to the prevention or treatment of fatty overloads, in particular of cellulite.
  • the aforementioned slimming compositions also contain other active substances, such as xanthines, in particular caffeine, an ivy extract CHedera Hellix), or an extract of Coleus, in particular of Coleus forskolii.
  • the cosmetic or pharmaceutical compositions according to the invention intended for topical administration are advantageously formulated with a particular excipient playing the role of penetration vector, that is to say an agent promoting penetration and diffusion to the level of the cutaneous structures concerned such as those commonly used in the fields of cosmetology and dermo-pharmacy such as, for example, ethyl alcohol, a glycol, in particular glycerol or propylene- glycol, oleic acid, laurocapram, or an essential oil, especially menthol or eucalyptol.
  • a particular excipient playing the role of penetration vector that is to say an agent promoting penetration and diffusion to the level of the cutaneous structures concerned such as those commonly used in the fields of cosmetology and dermo-pharmacy such as, for example, ethyl alcohol, a glycol, in particular glycerol or propylene- glycol, oleic acid, laurocapram, or an essential oil, especially menthol or eucalypto
  • a cosmetic or pharmaceutical composition according to the invention intended more particularly for the pigmentation of the skin or the hair, additionally contains a xanthine, in particular 1-methylxanthine, 3-methylxanthine, 3-isobutylmethylxanthine or theophylline, preferably at a weight concentration of between 0.001% and 2%, and more preferably between 0.01% and 0.5%, relative to the total weight of the composition.
  • a xanthine in particular 1-methylxanthine, 3-methylxanthine, 3-isobutylmethylxanthine or theophylline
  • a cosmetic or pharmaceutical composition according to the invention also contains tyrosine or one of its derivatives such as glucose tyrosinate, N-malyltyrosine, preferably at a weight concentration of between 0.001% and 10%, relative to the total weight of the composition.
  • a cosmetic or pharmaceutical composition according to the invention also contains at least one other active substance, at an effective concentration, chosen from vitamins, in particular vitamins B, quinine or its derivatives, rubefiants, such as methyl nicotinate, a culture supernatant of papilla fibroblasts, as defined in document EP-A-272 920, hydrolysates of keratin, trace elements such as zinc, selenium, copper, 5-oc-reductase inhibitors, such as progesterone, cyproterone acetate, minoxidil, azelaic acid and its derivatives, 1, 4-methyl-4-azasteroid, in particular 17 - ⁇ -N, N-diethylcarbamoyl-4-methyl-4-aza-5- ⁇ -androstan-3-one, or an extract of Serenoa repens.
  • vitamins in particular vitamins B, quinine or its derivatives, rubefiants, such as methyl nicotinate, a culture supernatant of papill
  • a cosmetic or pharmaceutical composition according to the invention also contains hydrated lipid Lamellar phases or liposomes, incorporating or not incorporating the Ballota nigra extract previously defined.
  • the present invention also relates to a process for the manufacture of a cosmetic or pharmaceutical composition, in particular dermatoLogique, intended in particular for promoting pigmentation of the skin, preventing or slowing the appearance of white hair, treating pigmentation disorders of the skin or hair; reduce the amount of tri ⁇ glycerides in adipocytes, avoid the development of fatty accumulations in the body, such as cellulite, characterized in that it comprises the incorporation of at least one extract of bundle as previously defined in a cosmetically or pharmaceutically acceptable excipient, vehicle or support.
  • the invention relates to the use of an extract of bundle, as defined above, for the preparation of a cosmetic or pharmaceutical composition, in particular dermatological, intended in particular to promote the pigmentation of the skin. , to prevent or slow the appearance of white hair, to treat disorders of pigmentation of the skin or hair; to reduce the amount of triglycerides in adipocytes, to avoid the development of fatty accumulations in the body, such as cellulite.
  • the present invention also relates to a cosmetic or therapeutic treatment method for an insufficiency or disorders of pigmentation, characterized in that it comprises the application of an effective amount of at least an extract of bundle as previously defined, advantageously incorporated in an excipient, vehicle or carrier which is cosmetically or pharmaceutically acceptable, preferably on the areas concerned of the skin or scalp of a human being, in order to restore normal pigmentation of the skin or hair and / or to increase this pigmentation.
  • the present invention also relates to a process for the treatment of melanocytes in culture, in particular human melanocytes in culture, with a view to making them acquire maturation characters suitable for later use, characterized in that that he understands culture said melanocytes in a culture medium comprising an effective quantity of at least one bale extract for a period of time sufficient to obtain a differentiation of the melano ⁇ cytes.
  • the present invention relates to a cosmetic or therapeutic treatment process consisting of grafts of melanocytes in a mammal, preferably in humans, characterized in that grafts of melanocytes, in particular of Human melanocytes, which have undergone differentiation by culture in the presence of an effective amount of differentiation of at least one bundle extract as defined above.
  • the present invention relates to a method of " cosmetic or therapeutic treatment for reducing the quantity " of triglycerides in the adipocytes of a mammal, in particular of a human being, characterized in that it comprises the application as a preventive or curative to the areas to be treated, of an amount effective to reduce the amount of tri ⁇ glycerides in adipocytes, in particular to inhibit their synthesis by these cells, of at least one extract of bundle such as previously defined, optionally in a cosmetically or pharmaceutically acceptable excipient, vehicle or support.
  • the invention also covers a method of preventing or treating fatty overloads, in particular of the cellu ⁇ lite, characterized in that it comprises the application to the areas of the body of a mammal, in particular of a being human, suffering from fatty overloads in the body, such as cellu ⁇ lite, of an amount effective to obtain the reduction of said fatty overloads, of at least one bundle extract as defined above, possibly in an excipient, vehicle or cosmetically or pharmaceutically acceptable carrier.
  • the bundle extract as defined above, can be used in the presence of hydrated lipid lamellar phases or of Liposomes, incorporating or not incorporating said extract. It is specified that the expression "incorporating” covers the case where the extract is fully incorporated and that or only a certain quantity of this extract is incorporated in the hydrated lipidic Lamellar phases or in The Liposomes.
  • Lipid in the expression “lipidic lamellar phase” covers all substances comprising a said car ⁇ bonée fatty chain generally containing more than 5 carbon because ⁇ bone, this substance usually being called "lipid.”
  • amphiphilic lipids are used as lipid, to form the lipidic lamellar phases, or the liposomes, that is to say made up of molecules having a hydrophilic group either ionic or nonionic and a Lipophilic group, these amphiphilic lipids being capable of forming lipid lamellar phases or Liposomes, in the presence of an aqueous phase, depending on the amount of water in the mixture.
  • these lipids there may be mentioned: phospholipids, phosphoaminolipids, glycolipids.
  • Such substances consist, for example, of an egg or soy lecithin, a serine phosphatidyl, a sphyngomyelin, a cerebroside or an oxyethylenated polyglycerol stearate.
  • a lipid mixture which consists of at least one amphiphilic lipid and at least one hydrophobic lipid such as steroid, such as cholesterol or ⁇ -sitosteroL.
  • the amount, expressed in moles, of hydrophobic lipid should generally not be greater than the amount of amphiphilic lipid, and preferably it should not be greater than 0.5 times this amount.
  • extract _ 2 an ethyl acetate extract from Ballota nigra called extract _ 2 is obtained.
  • the mixture thus obtained is evaporated in a rotary flask at a temperature of 60 ° C. under reduced pressure.
  • the lipid film thus obtained is then taken up and dispersed with stirring in distilled water qs 50 g, at room temperature for 12 h.
  • the suspension of lipid vesicles obtained is then homogenized by ultrasonic treatment for 10 min at 4 ° C., at a power of 150 W.
  • the average size of the liposomes thus obtained is approximately 140 nm.
  • this suspension is then gelled by mixing it with 50 g of (S) CarbopoL ⁇ 940 gel at 1.25% prepared separately in a conventional manner.
  • composition I This gel is called “composition I” and can be used as it is in the context of the invention.
  • 10 cells per dish are cultured in EMEM medium supplemented with nonessential amino acids and also containing 1% of fetal calf serum and 0.08 ⁇ g / ml of Mitomycin C. 24 h after sowing, The culture medium is replaced by fresh medium without Mitomycin C, comprising only EMEM medium which is supplemented, 1% calf serum fetal and, where appropriate, the product to be tested dissolved in DMS0, at a concentration of approximately 40 mg / ml.
  • the cells are removed which are isolated by centrifugation and the cell is recovered. This cell is dissolved in 0.5 N sodium hydroxide, in sufficient proportion to obtain essentially the same concentration in weight of cells per milliliter of final solution.
  • the optical density of the solution obtained is read on a spectrophotometer at 405 nm, which makes it possible to evaluate the amount of melanin formed by comparison with the optical density of a melanin solution of known concentration. .
  • the cells are also counted, and the amount of melanin formed per 10 cells is calculated.
  • the extracts I- and I-, of Ballota nigra were tested, at various concentrations in micrograms ( ⁇ g) per milliliter, which is also mentioned in Tables I and II below.
  • melanocytes used in the present tests responded positively to beta-MSH (Melanocyte-Stimulating Hormone).
  • NS not significant at 5%.
  • the pigmentation process of the cutaneous epidermis involves the differentiation of the melanocytes located in the basal layer of the epidermis.
  • stages I to IV
  • Stage IV (The most colorful) is the final stage of pigment loading of the melanosomes, which we therefore considers it to be mature.
  • melanin contained in the melanosomes is transferred to the keratinocytes situated at a higher level of the epidermis, through dendritic extensions of the melanocytes.
  • Normal human melanocytes conventionally isolated from a facelift from a 50 year old woman, are cultured on day D 0, in medium M 199 CGIBCO) complete, comprising 10% V / V of fetal calf serum and supplemented with factors growth charts.
  • the resin blocks are then cut into ultrafine sections using a microtome.
  • the ultrastructure of the cells can thus be observed by transmission electron microscopy.
  • control culture mainly presents stage I and II melanosomes.
  • the reticuloendothelial system and the Golgi apparatus appear to be not very active.
  • the culture treated presents numerous mela ⁇ nosomes having reached stages III and IV, in the majority of the cells.
  • the reticuloendothelial system and endothelial cells Golgi apparatus, at which occurs the synthadose of tyro- Sinase, its glycosylation and the formation of secretory vesicles melanin, are very developed, and therefore very active. All these characteristics reflects the existence of Melano ⁇ cytes differentiated, particularly in the extent that they have many mature melanosomes, in stages III and IV.
  • the demonstration of a mechanism of action of bundle extracts makes it possible, on the one hand, to explain the activity of the compositions according to the invention promoting skin pigmentation, and on the other hand, authorizes the setting implementation of a process for obtaining, in culture, more differentiated melanocytes with melanomas of high maturity, these melanocytes can then be used in grafts to treat certain pigmentation disorders, such as vitiligo.
  • Example 6 Demonstration of the inhibitory activity of the products of the Inventory ⁇ vis-à-vis the accumulation of triglycerides in adi ⁇ pocytes
  • Triglycerides which constitute an important energy reserve for the body, are formed from glycerol and fatty acids, in the intestinal wall, the liver and adipose tissues.
  • the fatty deposits of the organism are directly linked to the accumulation of triglycerides in adipocytes.
  • certain fibroblast lines in culture in particular the 3T3-L1 line, are capable of differentiating into adipocytes when the culture conditions are permissive (for example according to the technique described by Teruo Kawada et al., in Comp. Biochem. Physiol. (1990) vol. 96A, N.2, pp. 323-326).
  • this culture medium contains the products to be tested, with the exception of the medium corresponding to the control cultures.
  • the triglycerides present in the cultures are extracted with heptane.
  • the cells in culture are first removed from their box, in a conventional manner using a solution of trypsin.
  • the cell suspension thus obtained is then lysed by adding a sufficient amount of Dole CDole reagent V.P. et al., Journal of Biological Chemistry C1960) vol. 235, N.9, pp. 2595).
  • Water is then added, then heptane to the preparation, which makes it possible to obtain two phases: one aqueous and the other organic consisting of heptane.
  • the latter, containing the triglycerides present in the culture is then collected, and its radioactivity is determined in liquid scintillation, for example by means of a device of the 0NTR0N BETA V® type.
  • the activity A of the products of the invention is calculated according to the following formula:
  • R representing the radioactivity of the triglyceride extracts of the control cultures, expressed in cpm (counts per minute), and R representing that of the cultures in the presence of the product according to the invention, also expressed in cpm.
  • the product of the invention which was the subject of this test consists of the methanolic extract I. of bundle, obtained according to Example 1.
  • Table III below presents the results of the inhibitory activity of extract I. at two different concentration values in the cultures.
  • the products of the invention can be advantageously used as active principle in cosmetic compositions. ticks or pharmaceuticals, especially dermatological, for the prevention or treatment of fatty overloads, in particular ⁇ Cellulite.
  • the preparation of the gel is carried out from two phases, respectively A and B, as follows:
  • Phase A is gradually added to Phase B and mixed with a propeller stirrer until completely dispersed.
  • a gel promoting the tanning of the skin is thus obtained, which can be applied before or during sun exposure.
  • the ballot extract is first dissolved in alcohol, then the whole is incorporated into a gelled excipient containing the Carbopol. A slimming composition is thus obtained which can be applied to the areas to be treated.

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Abstract

L'invention concerne l'utilisation d'un extrait de ballote. Plus particulièrement, l'invention concerne l'utilisation d'un extrait de ballote pour la préparation d'une composition cosmétique ou pharmaceutique, notamment dermatologique, destinée en particulier à favoriser la pigmentation de la peau, à prévenir ou ralentir l'apparition des cheveux blancs, à traiter les désordres de la pigmentation; à réduire la quantité de triglycérides dans les adipocytes, à éviter le développement d'accumulations graisseuses dans l'organisme, telles que la cellulite. L'invention permet ainsi en particulier de favoriser de manière efficace la pigmentation de la peau ou des cheveux ou la réduction des accumulations graisseuses dans l'organisme, telles que la cellulite.The invention relates to the use of a bundle extract. More particularly, the invention relates to the use of a bundle extract for the preparation of a cosmetic or pharmaceutical composition, in particular a dermatological composition, intended in particular to promote pigmentation of the skin, to prevent or slow the appearance of hair. white, to treat pigmentation disorders; reduce the amount of triglycerides in fat cells, avoid the development of fatty accumulations in the body, such as cellulite. The invention thus makes it possible in particular to effectively promote the pigmentation of the skin or the hair or the reduction of fatty accumulations in the body, such as cellulite.

Description

Composition cosmétique ou pharmaceutique contenant un extrait de Bal loteCosmetic or pharmaceutical composition containing an extract of Bal lote
La présente invention concerne essentiellement une compo¬ sition cosmétique ou pharmaceutique, notamment dermatologique, con¬ tenant un extrait de ballote, destinée en particulier à favoriser la pigmentation de la peau ou des cheveux, ou à réduire la quantité de triglycérides dans les adipocytes et son procédé de fabrication.The present invention essentially relates to a cosmetic or pharmaceutical composition, in particular a dermatological composition, containing an extract of bundle, intended in particular for promoting pigmentation of the skin or hair, or for reducing the amount of triglycerides in adipocytes and its manufacturing process.
La présente invention concerne aussi l'utilisation d'un extrait de ballote pour la préparation d'une telle composition cosmétique ou pharmaceutique, en particulier destinée à traiter les troubles de la pigmentation ou pour réduire la quantité de tri- glycérides dans les adipocytes.The present invention also relates to the use of a bundle extract for the preparation of such a cosmetic or pharmaceutical composition, in particular intended for treating pigmentation disorders or for reducing the amount of triglycerides in adipocytes.
Les plantes du genre ballote font partie de la famille des labiées, des régions tempérées. On peut citer, par exemple, Ballota nigra (LINN.) ou Ballota foetida ou encore Marrube noir (en anglais "black horehound"). Il s'agit d'une plante vivace com- mune qui se rencontre surtout dans les lieux incultes, le long des haies, de chemins ou des murs. Elle possède une odeur fortement désagréable. On peut encore citer Ballota lanata, cultivée dans les jardins, et Ballota suavelens ou ballote odorante, préconisée comme emmanagogue et anti-hystérique. La tradition attribue à la ballote des propriétés tonique, stomachique, antispasmodique, calmante, dépurative, diuré¬ tique, vermifuge, résolutive et détersive.Plants of the genus ballote are part of the family of labiates, from temperate regions. We can cite, for example, Ballota nigra (LINN.) Or Ballota foetida or even Black horehound (in English "black horehound"). It is a common perennial that occurs mainly in uncultivated places, along hedges, paths or walls. It has a strongly unpleasant odor. We can also cite Ballota lanata, cultivated in gardens, and Ballota suavelens or fragrant ballot, recommended as an emmanagogue and anti-hysteric. The tradition attributes to the bundle tonic, stomachic, antispasmodic, calming, depurative, diuretic, anthelmintic, resolving and detersive properties.
La présente invention est basée sur la découverte que les extraits de ballote, provenant de la plante entière, et notamment des parties aériennes et en particulier des tiges et des feuilles, présentent des propriétés biologiques intéressantes utilisables dans les domaines cosmétique et pharmaceutique. Il a notamment été observé par les inventeurs que ces extraits possédaient de façon inattendue une activité stimulante de la mélanogénèse, au niveau des mélanocytes présents dans la peau ou les follicules pileux, notamment ceux du cuir chevelu, et permettaient ainsi de favoriser la pigmentation de la peau ou des cheveux, ainsi que de réaliser un traitement des désordres de la pigmentation de la peau et des cheveux en favorisant plus particulièrement la bio¬ synthèse de mélanine. De très bons résultats dans ce domaine ont été obtenus avec des extraits de la plante entière, et notamment des parties aériennes et en particulier des tiges et des feuilles de ballote.The present invention is based on the discovery that the bundle extracts, originating from the whole plant, and in particular from the aerial parts and in particular from the stems and leaves, have interesting biological properties which can be used in the cosmetic and pharmaceutical fields. It has in particular been observed by the inventors that these extracts unexpectedly possess a stimulating activity of melanogenesis, at the level of the melanocytes present in the skin or the hair follicles, in particular those of the scalp, and thus make it possible to favor the pigmentation of the skin or the hair, as well as carry out a treatment of the pigmentation disorders of the skin and the hair by more particularly promoting the bio¬ synthesis of melanin. Very good results in this area have been obtained with extracts from the whole plant, and in particular from the aerial parts and in particular from the stems and leaves of bundles.
Egalement, il a été observé par les inventeurs que les extraits précités de ballote possédaient de façon inattendue une activité réduisant la quantité de triglycérides dans Les adipo- cytes, notamment en inhibant Leur synthèse au niveau de ces cel¬ lules. Ces extraits permettent ainsi d'éviter le développement d'accumulations graisseuses dans l'organisme, telles que la cellu¬ lite, et sont ainsi particulièrement utilespour préparer des compo- sitions cosmétiques ou pharmaceutiques, notamment dermatologiques, amincissantes.Also, it has been observed by the inventors that the abovementioned extracts of bundle unexpectedly possess an activity reducing the amount of triglycerides in adipocytes, in particular by inhibiting their synthesis in these cells. These extracts thus make it possible to avoid the development of fatty accumulations in the organism, such as cellu¬ lite, and are thus particularly useful for preparing cosmetic or pharmaceutical compositions, in particular dermatological, slimming preparations.
La présente invention a donc pour but de résoudre Le nouveau problème technique consistant en La fourniture d'une nouvelle composition cosmétique ou pharmaceutique, notamment dermatologique, destinée en particulier à favoriser La pigmentation de La peau, à prévenir ou ralentir l'apparition des cheveux blancs.The present invention therefore aims to solve the new technical problem consisting in the supply of a new cosmetic or pharmaceutical composition, especially dermatological, intended in particular to promote pigmentation of the skin, to prevent or slow the appearance of white hair. .
La présente invention a encore pour but de résoudre Le nouveau problème technique consistant en La préparation d'une nouvelLe formulation d'une composition cosmétique ou pharmaceutique présentant une bonne activité de stimuLation de La méLanogenese au niveau des méLanocytes présents dans La peau ou dans Les follicules pileux, notamment ceux du cuir cheveLu.Another object of the present invention is to solve the new technical problem consisting in the preparation of a new formulation of a cosmetic or pharmaceutical composition having a good activity for stimulating melanogenesis in the melanocytes present in the skin or in the follicles. hair, especially those of the scalp.
La présente invention a encore pour but de fournir une solution au nouveau problème technique consistant en la fourniture d'un extrait de plante particulièrement aisé à obtenir, qui pré¬ sente en lui-même une bonne activité stimulante de La méLanogenese, au niveau des méLanocytes présents dans La peau ou Les follicules pileux, sans avoir à réaliser l'isolement d'une substance active quelconque, ces procédés d'isolement étant en général longs et coûteux. La présente invention a encore pour but de résoudre le nouveau problème technique consistant en la préparation d'une nouvelle formulation d'une composition cosmétique ou pharmaceutique présentant une bonne activité réduisant la quantité de tπ'glycé- rides dans les adipocytes, en permettant ainsi d'éviter le dévelop¬ pement d'accumulations graisseuses dans l'organisme, telles que la cellulite.The present invention also aims to provide a solution to the new technical problem consisting in the supply of a plant extract which is particularly easy to obtain, which in itself exhibits a good stimulating activity of melanogenesis, at the level of melanocytes. present in the skin or hair follicles, without having to perform the isolation of any active substance, these isolation procedures are generally long and expensive. The present invention also aims to solve the new technical problem consisting in the preparation of a new formulation of a cosmetic or pharmaceutical composition having a good activity reducing the amount of tπ ' glycerides in adipocytes, thus allowing d 'avoid the development of fatty accumulations in the body, such as cellulite.
La présente invention a encore pour but de fournir une solution au nouveau problème technique consistant en la fourniture d'un extrait de plante particulièrement aisé à obtenir, qui pré¬ sente lui-même une bonne activité réduisant la quantité de trigly¬ cérides dans les adipocytes, sans avoir à réaliser l'isolement d'une substance active quelconque, ces procédés d'isolement étant généralement longs et coûteux. Tous ces nouveaux problèmes techniques sont résolus pourThe present invention also aims to provide a solution to the new technical problem consisting in the supply of a plant extract which is particularly easy to obtain, which itself exhibits a good activity reducing the amount of trigly¬ cerides in the adipocytes. , without having to carry out the isolation of any active substance, these isolation methods being generally long and costly. All these new technical problems are solved for
La première fois par la présente invention d'une manière satisfaisante, utilisable à l'échelle industrielle.The first time by the present invention in a satisfactory manner, usable on an industrial scale.
Ainsi, selon un premier aspect, la présente invention concerne une composition cosmétique ou pharmaceutique, notamment dermatologique, destinée en particulier à favoriser la pigmentation de la peau, à prévenir ou ralentir l'apparition des cheveux blancs ; à réduire la quantité de triglycérides dans les adipo¬ cytes, à éviter le développement de l'accumulation graisseuse dans l'organisme, telle que la cellulite, caractérisée en ce qu'elle comprend à titre d'ingrédient actif une quantité cosmétiquement ou pharmaceutiquement efficace d'un extrait de ballote, éventuellement dans un excipient cosmétiquement ou pharmaceutiquement acceptable.Thus, according to a first aspect, the present invention relates to a cosmetic or pharmaceutical composition, in particular a dermatological composition, intended in particular to promote pigmentation of the skin, to prevent or slow down the appearance of white hair; reduce the amount of triglycerides in adipocytes, avoid the development of fatty accumulation in the body, such as cellulite, characterized in that it comprises, as active ingredient, a cosmetically or pharmaceutically effective amount a bundle extract, optionally in a cosmetically or pharmaceutically acceptable excipient.
Dans la présente description et les revendications, on entend par "quantité cosmétiquement ou pharmaceutiquement efficace" une quantité au moins égale à la quantité minimale qui est néces¬ saire pour observer un effet significatif, respectivement cosmé¬ tique ou pharmaceutique.In the present description and the claims, the term "cosmetically or pharmaceutically effective amount" means an amount at least equal to the minimum amount which is necessary to observe a significant effect, respectively cosmetic or pharmaceutical.
Avantageusement, l'extrait de ballote est choisi parmi Les extraits de Ballota nigra, de Ballota lanata et de Ballota suavelens. Selon une caractéristique particulière de l'invention, l'extrait de ballote est choisi parmi un extrait de La plante entière, et un extrait des parties aériennes, en particulier essen¬ tiellement des tiges et des feuilles. Selon une autre caractéristique, l'extrait de ballote précité est un extrait obtenu avantageusement par un procédé com¬ prenant au moins une étape d'extraction avec par exemple un solvant choisi parmi le groupe constitué par l'eau, Les alcools comportant de préférence de 1 à 4 atomes de carbone tels que Le méthanol, l'éthanol ou le propanol, un mélange hydroalcoolique de ces alcools, les solvants chlorés comportant 1 ou 2 atomes de carbone tels que Le chloroforme ou le dichlorométhane, Les esters orga¬ niques comportant de préférence 3 à 6 atomes de carbone tels que L'acétate d'éthyle. D'une façon plus générale, on peut utiliser également comme solvant, des solvants organiques tels que les hydrocarbures aromatiques, notamment Le benzène, Le toluène ou le xylène, des hydrocarbures aliphatiques ou aromatiques halogènes, des éthers dialcoyliques, des dialcoylcétones, des alcanols, des acides carboxyliques et Leurs esters ou d'autres solvants, comme le diméthylformamide. Le dioxanne. Le tétrahydrofuranne et le diméthyLsulfoxyde, ou encore le gaz carbonique supercritique. Le rapport de La matière végétale à l'agent d'extraction peut être choisi dans une large gamme, toutefois il est généralement compris entre 1:5 et 1:20 parties en poids, et iL est préférentielLement de 1:10 environ. L'extraction s'effectue à des températures comprises entre La température ambiante et Le point d'ébullition du solvant utilisé pour L'extraction. Une technique intéressante d'extraction est La technique dite d'extraction au Soxhlet.Advantageously, the ballote extract is chosen from extracts of Ballota nigra, Ballota lanata and Ballota suavelens. According to a particular characteristic of the invention, the bale extract is chosen from an extract of the whole plant, and an extract from the aerial parts, in particular essen¬ tially from the stems and leaves. According to another characteristic, the above-mentioned bundle extract is an extract advantageously obtained by a process comprising at least one extraction step with, for example, a solvent chosen from the group consisting of water, The alcohols preferably comprising 1 to 4 carbon atoms such as methanol, ethanol or propanol, a hydroalcoholic mixture of these alcohols, chlorinated solvents containing 1 or 2 carbon atoms such as chloroform or dichloromethane, organic esters comprising preferably 3 to 6 carbon atoms such as ethyl acetate. More generally, it is also possible to use as solvent, organic solvents such as aromatic hydrocarbons, in particular benzene, toluene or xylene, aliphatic or halogenated aromatic hydrocarbons, dialkyl ethers, dialkyl ketones, alkanols, carboxylic acids and their esters or other solvents, such as dimethylformamide. Dioxane. Tetrahydrofuran and dimethyl sulfoxide, or even supercritical carbon dioxide. The ratio of the plant material to the extractant can be chosen from a wide range, however it is generally between 1: 5 and 1:20 parts by weight, and it is preferably approximately 1:10. The extraction is carried out at temperatures between ambient temperature and the boiling point of the solvent used for the extraction. An interesting extraction technique is the so-called Soxhlet extraction technique.
Mais on peut également, de manière simple, effectuer L'extraction- à reflux sous pression atmosphérique normale pendant 2 à 4 h, après avoir éventuellement laissé macérer la matière végé¬ tale à froid pendant 2 à 4 h dans Le solvant d'extraction.But it is also possible, in a simple manner, to carry out the extraction at reflux under normal atmospheric pressure for 2 to 4 hours, after having optionally left the vegetable material to macerate cold for 2 to 4 hours in the extraction solvent.
En fin d'extraction, la phase contenant l'extrait est filtrée, puis concentrée et/ou évaporée à sec sous pression réduite ou par Lyophilisation.At the end of extraction, the phase containing the extract is filtered, then concentrated and / or evaporated to dryness under reduced pressure or by lyophilization.
On obtient ainsi un extrait selon l'invention. D'une façon générale, la concentration des extraits utilisés conformément à la présente invention, pour la préparation d'une composition cosmétique ou pharmaceutique, exprimée en poids sec est comprise entre 0,0001 % et 5 % en poids, de préférence entre 0,01 % et 0,5 % en poids, par rapport au poids total de la composition.An extract according to the invention is thus obtained. In general, the concentration of the extracts used in accordance with the present invention, for the preparation of a cosmetic or pharmaceutical composition, expressed in dry weight is between 0.0001% and 5% by weight, preferably between 0, 01% and 0.5% by weight, relative to the total weight of the composition.
Les compositions cosmétiques ou pharmaceutiques, notam¬ ment dermatologiques, selon la présente invention, peuvent être préparées sous des formes convenant à divers modes d'administra- tion. En particulier, elles peuvent se présenter sous une forme destinée à l'administration super icielle sur la peau ou le cuir chevelu, telle qu'une crème, un gel, un lait ou une lotion, afin de favoriser la pigmentation de la peau, de prévenir ou ralentir l'apparition des cheveux blancs. Ainsi, les compositions cosmétiques ou pharmaceutiques, notamment dermatologiques, selon l'invention trouvent diverses applications en cosmétologie ou en pharmacie notamment en dermato¬ logie, en particulier Lorsque la restauration de la pigmentation normale ou son augmentation est recherchée. Par exemple, ces compositions peuvent être utilisées comme produits solaires pour accélérer ou intensifier le bronzage, ce qui, outre l'avantage esthétique souvent recherché, permet de renforcer les défenses naturelles contre le rayonnement ultraviolet par l'augmentation du taux de mélanine dans l'épiderme. Ces compositions peuvent encore être utilisées, par exemple sous forme de crèmes, pour donner à la peau un aspect plus hâlé, ou encore, sous forme de lotions, pour La prévention ou le ralentissement de l'apparition des cheveux blancs. Par ailleurs, en dermatologie, les compositions selon la présente invention peuvent être utilisées comme agents thérapeutiques, seules ou en association avec d'autres médicaments, en particulier en administration topique dans le traitement des dysfonctionnements des méLanocytes.The cosmetic or pharmaceutical, in particular dermatological, compositions according to the present invention can be prepared in forms suitable for various modes of administration. In particular, they can be in a form intended for super administration here on the skin or the scalp, such as a cream, a gel, a milk or a lotion, in order to promote the pigmentation of the skin, prevent or slow the appearance of gray hair. Thus, the cosmetic or pharmaceutical, in particular dermatological, compositions according to the invention find various applications in cosmetology or in pharmacy in particular in dermato¬ logy, in particular When the restoration of normal pigmentation or its increase is sought. For example, these compositions can be used as sunscreen products to accelerate or intensify tanning, which, in addition to the aesthetic advantage often sought after, makes it possible to strengthen the natural defenses against ultraviolet radiation by increasing the level of melanin in the epidermis. These compositions can also be used, for example in the form of creams, to give the skin a more tanned appearance, or alternatively, in the form of lotions, for preventing or slowing the appearance of white hair. Furthermore, in dermatology, the compositions according to the present invention can be used as therapeutic agents, alone or in combination with other drugs, in particular in topical administration in the treatment of dysfunctions of melanocytes.
En ce qui concerne l'action chez les méLanocytes, il a pu être mis en évidence que les extraits selon l'invention permet- taient de favoriser la différenciation des méLanocytes, c'est-à- dire de favoriser l'obtention de mélanosomes plus matures ou mieux différenciés dans des cultures de méLanocytes humains.With regard to the action in melanocytes, it has been possible to demonstrate that the extracts according to the invention make it possible to promote the differentiation of melanocytes, that is to say say to favor the obtaining of more mature or better differentiated melanosomes in cultures of human melanocytes.
Une application particul èrement intéressante réside dans une application de ces extraits selon l'invention dans une méthode de traitement de méLanocytes en culture, notamment de méLanocytes humains normaux en culture, en vue de leur faire acquérir des caractères de maturation convenables pour Leur utilisation ulté¬ rieure.A particularly interesting application resides in an application of these extracts according to the invention in a method of treatment of melanocytes in culture, in particular of normal human melanocytes in culture, with a view to making them acquire maturation characters suitable for their ultimate use. better.
En particule _r, l'utilisation ultérieure peut consister en des greffe de méLanocytes chez L'homme, notamment pour traiter certains troubles de La pigmentation, tels que le vitiligo.In particular, the subsequent use can consist of melanocyte transplants in humans, in particular for treating certain pigmentation disorders, such as vitiligo.
Par ailleurs, les compositions cosmétiques ou pharmaceu¬ tiques, notamment dermatologiques, selon l'invention trouvent aussi diverses applie -ions en cosmétologie ou en pharmacie notamme* en dermatologie, r.otamment en administration topique, pour réd: La quantité de triglycérides dans Les adipocytes. On sait en i- culier que La synthèse des triglycérides par Les adipocytes va de paire avec Le développement d'accumulations graisseuses dans L'organisme, telles que la celLulite. Ainsi, Les extraits selon L'invention trouvent une application particulièrement intéressante dans des compositions cosmétiques ou pharmaceutiques, notamment dermatologiques, amincissantes, en vue de la prévention ou du trai¬ tement des surcharges graisseuses, en particulier de la cellulite. Avantageusement, les compositions amincissantes précitées contiennent en outre d'autres substances actives, telles que des xanthines, en particulier la caféine, un extrait de lierre CHedera Hellix), ou un extrait de Coleus, en particulier de Coleus forskolii.Moreover, cosmetic or pharmaceu¬ ticks, especially dermatological, the invention also include various applie -ions in cosmetology or pharmacy notamme * dermatology r.otamment topical administration, for drafted: The amount of triglycerides in the fat cells. It is known in particular that The synthesis of triglycerides by adipocytes goes hand in hand with the development of fatty accumulations in the organism, such as celLulite. Thus, the extracts according to the invention find a particularly advantageous application in cosmetic or pharmaceutical, in particular dermatological, slimming compositions, with a view to the prevention or treatment of fatty overloads, in particular of cellulite. Advantageously, the aforementioned slimming compositions also contain other active substances, such as xanthines, in particular caffeine, an ivy extract CHedera Hellix), or an extract of Coleus, in particular of Coleus forskolii.
Avantageusement, les compositions cosmétiques ou pharma- ceutiques selon l'invention destinées à L'administration topique sont avantageusement formulées avec un excipient particulier jouant le rôle de vecteur de pénétration, c'est-à-dire un agent favorisant La pénétration et La diffusion au niveau des structures cutanées concernées tel que ceux utilisés couramment dans les domaines de La cosmétologie et de La dermo-pharmacie comme par exemple, L'alcool éthylique, un glycol, en particulier Le glycérol ou Le propylène- glycol, l'acide oléique, le laurocapram, ou une huile essentielle, notamment le menthol ou l 'eucalyptol.Advantageously, the cosmetic or pharmaceutical compositions according to the invention intended for topical administration are advantageously formulated with a particular excipient playing the role of penetration vector, that is to say an agent promoting penetration and diffusion to the level of the cutaneous structures concerned such as those commonly used in the fields of cosmetology and dermo-pharmacy such as, for example, ethyl alcohol, a glycol, in particular glycerol or propylene- glycol, oleic acid, laurocapram, or an essential oil, especially menthol or eucalyptol.
Selon un mode de réalisation avantageux, une composition cosmétique ou pharmaceutique selon l'invention, destinée plus par- ticulièrement à la pigmentation de la peau ou des cheveux, contient en outre une xanthine, en particulier la 1-méthylxanthine, la 3- méthylxanthine, la 3-isobutylméthylxanthine ou la théophylline, de préférence à une concentration pondérale comprise entre 0,001% et 2%, et encore de préférence comprise entre 0,01% et 0,5%, par rap- port au poids total de la composition.According to an advantageous embodiment, a cosmetic or pharmaceutical composition according to the invention, intended more particularly for the pigmentation of the skin or the hair, additionally contains a xanthine, in particular 1-methylxanthine, 3-methylxanthine, 3-isobutylmethylxanthine or theophylline, preferably at a weight concentration of between 0.001% and 2%, and more preferably between 0.01% and 0.5%, relative to the total weight of the composition.
Selon un autre mode de réalisation, en particulier appli¬ cable dans le cadre d'une activation de la pigmentation de la peau ou des cheveux, une composition cosmétique ou pharmaceutique selon l'invention contient en outre de la tyrosine ou l'un de ses dérivés tel que le tyrosinate de glucose, la N-malyltyrosine, de préférence à une concentration pondérale comprise entre 0,001% et 10%, par rapport au poids total de la composition.According to another embodiment, in particular appli¬ cable in the context of an activation of the pigmentation of the skin or the hair, a cosmetic or pharmaceutical composition according to the invention also contains tyrosine or one of its derivatives such as glucose tyrosinate, N-malyltyrosine, preferably at a weight concentration of between 0.001% and 10%, relative to the total weight of the composition.
Selon encore un autre mode de réalisation, en particulier applicable dans le cadre d'une activation de la pigmentation des cheveux, une composition cosmétique ou pharmaceutique selon l'invention contient en outre au moins une autre substance active, à une concentration efficace, choisie parmi les vitamines, en particulier les vitamines B, la quinine ou ses dérivés, les rubéfiants, tels que le nicotinate de méthyle, un surnageant de culture de fibroblastes de papille, tel que défini dans le document EP-A-272 920, des hydrolysats de kératine, des oligoéléments tels que zinc, sélénium, cuivre, des inhibiteurs de 5-oc-réductase, tels que progestérone, cyprotérone acétate, minoxidil, acide azélaîque et ses dérivés, 1 ,4-méthyl-4-azastéroïde, en particulier la 17-β-N, N-diéthylcarbamoyl-4-méthyl-4-aza-5-α-androstan-3-one, ou encore un extrait de Serenoa repens.According to yet another embodiment, in particular applicable in the context of activation of hair pigmentation, a cosmetic or pharmaceutical composition according to the invention also contains at least one other active substance, at an effective concentration, chosen from vitamins, in particular vitamins B, quinine or its derivatives, rubefiants, such as methyl nicotinate, a culture supernatant of papilla fibroblasts, as defined in document EP-A-272 920, hydrolysates of keratin, trace elements such as zinc, selenium, copper, 5-oc-reductase inhibitors, such as progesterone, cyproterone acetate, minoxidil, azelaic acid and its derivatives, 1, 4-methyl-4-azasteroid, in particular 17 -β-N, N-diethylcarbamoyl-4-methyl-4-aza-5-α-androstan-3-one, or an extract of Serenoa repens.
Selon encore un autre mode de réalisation, une composi¬ tion cosmétique ou pharmaceutique selon l'invention contient en outre des phases Lamellaires lipidiques hydratées ou des liposomes, incorporant ou non l'extrait de Ballota nigra précédemment défini. Selon un deuxième aspect, la présente invention concerne encore un procédé de fabrication d'une composition cosmétique ou pharmaceutique, notamment dermatoLogique, destinée en particulier à favoriser la pigmentation de la peau, à prévenir ou ralentir l'apparition des cheveux blancs, à traiter Les désordres de La pig¬ mentation de la peau ou des cheveux ; à réduire la quantité de tri¬ glycérides dans les adipocytes, à éviter Le développement d'accumu¬ lations graisseuses dans l'organisme, telles que la cellulite, caractérisé en ce qu'il comprend l'incorporation d'au moins un extrait de ballote tel que précédemment défini dans un excipient, véhicule ou support cosmétiquement ou pharmaceutiquement acceptable.According to yet another embodiment, a cosmetic or pharmaceutical composition according to the invention also contains hydrated lipid Lamellar phases or liposomes, incorporating or not incorporating the Ballota nigra extract previously defined. According to a second aspect, the present invention also relates to a process for the manufacture of a cosmetic or pharmaceutical composition, in particular dermatoLogique, intended in particular for promoting pigmentation of the skin, preventing or slowing the appearance of white hair, treating pigmentation disorders of the skin or hair; reduce the amount of tri¬ glycerides in adipocytes, avoid the development of fatty accumulations in the body, such as cellulite, characterized in that it comprises the incorporation of at least one extract of bundle as previously defined in a cosmetically or pharmaceutically acceptable excipient, vehicle or support.
Selon un troisième aspect, L'invention concerne L'utili¬ sation d'un extrait de ballote, tel que précédemment défini, pour La préparation d'une composition cosmétique ou pharmaceutique, notamment dermatologique, destinée en particulier à favoriser la pigmentation de La peau, à prévenir ou ralentir L'apparition des cheveux blancs, à traiter Les désordres de La pigmentation de La peau ou des cheveux ; à réduire La quantité de triglycérides dans Les adipocytes, à éviter Le développement d'accumulations grais¬ seuses dans l'organisme, telles que La cellulite.According to a third aspect, the invention relates to the use of an extract of bundle, as defined above, for the preparation of a cosmetic or pharmaceutical composition, in particular dermatological, intended in particular to promote the pigmentation of the skin. , to prevent or slow the appearance of white hair, to treat disorders of pigmentation of the skin or hair; to reduce the amount of triglycerides in adipocytes, to avoid the development of fatty accumulations in the body, such as cellulite.
Selon encore un autre aspect, la présente invention con¬ cerne encore un procédé de traitement cosmétique ou thérapeutique d'une insuffisance ou de désordres de la pigmentation, caractérisé en ce qu'il comprend l'application d'une quantité efficace d'au moins un extrait de ballote tel que précédemment défini, avanta¬ geusement incorporé dans un excipient, véhicule ou support cosmé¬ tiquement ou pharmaceutiquement acceptable, de préférence sur Les zones concernées de La peau ou du cuir chevelu d'un être humain, afin de rétablir une pigmentation normale de La peau ou des cheveux et/ou pour augmenter cette pigmentation.According to yet another aspect, the present invention also relates to a cosmetic or therapeutic treatment method for an insufficiency or disorders of pigmentation, characterized in that it comprises the application of an effective amount of at least an extract of bundle as previously defined, advantageously incorporated in an excipient, vehicle or carrier which is cosmetically or pharmaceutically acceptable, preferably on the areas concerned of the skin or scalp of a human being, in order to restore normal pigmentation of the skin or hair and / or to increase this pigmentation.
Selon encore un autre aspect, La présente invention con¬ cerne encore un procédé de traitement de méLanocytes en culture, notamment de méLanocytes humains en culture, en vue de leur faire acquérir des caractères de maturation convenables pour une utilisa¬ tion ultérieure, caractérisé en ce qu'il comprend la culture desdits méLanocytes dans un milieu de culture comprenant une quan¬ tité efficace d'au moins un extrait de ballote pendant une période de temps suffisante pour obtenir une différenciation des méLano¬ cytes. Selon encore un autre aspect, la présente invention con¬ cerne un procédé de traitement cosmétique ou thérapeutique consis¬ tant en des greffes de méLanocytes chez un mammifère, de préférence chez l'homme, caractérisé en ce qu'on greffe des méLanocytes, notamment des méLanocytes humains, qui ont subi une différenciation par culture en présence d'une quantité efficace de différenciation d'au moins un extrait de ballote tel que précédemment défini.According to yet another aspect, the present invention also relates to a process for the treatment of melanocytes in culture, in particular human melanocytes in culture, with a view to making them acquire maturation characters suitable for later use, characterized in that that he understands culture said melanocytes in a culture medium comprising an effective quantity of at least one bale extract for a period of time sufficient to obtain a differentiation of the melano¬ cytes. According to yet another aspect, the present invention relates to a cosmetic or therapeutic treatment process consisting of grafts of melanocytes in a mammal, preferably in humans, characterized in that grafts of melanocytes, in particular of Human melanocytes, which have undergone differentiation by culture in the presence of an effective amount of differentiation of at least one bundle extract as defined above.
Selon encore un autre aspect, la présente invention con¬ cerne un procédé de" traitement cosmétique ou thérapeutique pour réduire la quantité "de triglycérides dans les adipocytes d'un mammifère, en particulier d'un être humain, caractérisé en ce qu'il comprend l'application à titre préventif ou curratif sur les zones à traiter, d'une quantité efficace pour réduire la quantité de tri¬ glycérides dans les adipocytes, en particulier pour inhiber leur synthèse par ces cellules, d'au moins un extrait de ballote tel que précédemment défini, éventuellement dans un excipient, véhicule ou support cosmétiquement ou pharmaceutiquement acceptable.According to yet another aspect, the present invention relates to a method of " cosmetic or therapeutic treatment for reducing the quantity " of triglycerides in the adipocytes of a mammal, in particular of a human being, characterized in that it comprises the application as a preventive or curative to the areas to be treated, of an amount effective to reduce the amount of tri¬ glycerides in adipocytes, in particular to inhibit their synthesis by these cells, of at least one extract of bundle such as previously defined, optionally in a cosmetically or pharmaceutically acceptable excipient, vehicle or support.
L'invention couvre encore un procédé de prévention ou du traitement des surcharges graisseuses, en particulier de la cellu¬ lite, caractérisé en ce qu'il comprend L'application sur les zones du corps d'un mammifère, en particulier d'un être humain, souffrant de surcharges graisseuses dans l'organisme, telles que la cellu¬ lite, d'une quantité efficace pour obtenir la réduction desdites surcharges graisseuses, d'au moins un extrait de ballote tel que précédemment défini, éventuellement dans un excipient, véhicule ou support cosmétiquement ou pharmaceutiquement acceptable.The invention also covers a method of preventing or treating fatty overloads, in particular of the cellu¬ lite, characterized in that it comprises the application to the areas of the body of a mammal, in particular of a being human, suffering from fatty overloads in the body, such as cellu¬ lite, of an amount effective to obtain the reduction of said fatty overloads, of at least one bundle extract as defined above, possibly in an excipient, vehicle or cosmetically or pharmaceutically acceptable carrier.
Dans tous les aspects précédents, L'extrait de ballote, tel que précédemment défini, peut être utilisé en présence de phases lamellaires lipidiques hydratées ou de Liposomes, incorpo¬ rant ou non ledit extrait. IL est précisé que l'expression "incorporant" couvre le cas où l'extrait est totalement incorporé et celui ou une certaine quantité seulement de cet extrait est incorporée dans les phases Lamellaires lipidiques hydratées ou dans Les Liposomes.In all of the foregoing aspects, the bundle extract, as defined above, can be used in the presence of hydrated lipid lamellar phases or of Liposomes, incorporating or not incorporating said extract. It is specified that the expression "incorporating" covers the case where the extract is fully incorporated and that or only a certain quantity of this extract is incorporated in the hydrated lipidic Lamellar phases or in The Liposomes.
Le terme "Lipidique" dans L'expression "phase lamellaire lipidique" couvre toutes Les substances comprenant une chaîne car¬ bonée dite grasse, comportant généralement plus de 5 atomes de car¬ bone, cette substance étant habituellement dénommée "lipide".The term "Lipid" in the expression "lipidic lamellar phase" covers all substances comprising a said car¬ bonée fatty chain generally containing more than 5 carbon because ¬ bone, this substance usually being called "lipid."
Selon l'invention, on utilise à titre de lipide, pour former Les phases Lamellaires lipidiques, ou Les Liposomes, des Lipides amphiphiles, c'est-à-dire constitués de moléculaires possé¬ dant un groupe hydrophile indifféremment ionique ou non ionique et un groupe Lipophile, ces lipides amphiphiles étant susceptibles de former des phases lamellaires lipidiques ou des Liposomes, en pré¬ sence d'une phase aqueuse, selon La quantité d'eau dans Le mélange. En particulier, parmi ces Lipides, on peut citer : Les phospholipides, les phosphoaminolipides, Les glycolipides. Les alcools gras polyoxyéthylénés, les esters de polyol éventuellement polyoxyéthylénés. De telles substances sont par exemple constituées par une Lécithine d'oeuf ou de soja, une phosphatidyle serine, une sphyngomyéLine, un cérébroside ou un stéarate de polyglycérol oxy- éthyléné.According to the invention, amphiphilic lipids are used as lipid, to form the lipidic lamellar phases, or the liposomes, that is to say made up of molecules having a hydrophilic group either ionic or nonionic and a Lipophilic group, these amphiphilic lipids being capable of forming lipid lamellar phases or Liposomes, in the presence of an aqueous phase, depending on the amount of water in the mixture. In particular, among these lipids, there may be mentioned: phospholipids, phosphoaminolipids, glycolipids. Polyoxyethylenated fatty alcohols, optionally polyoxyethylenated polyol esters. Such substances consist, for example, of an egg or soy lecithin, a serine phosphatidyl, a sphyngomyelin, a cerebroside or an oxyethylenated polyglycerol stearate.
De préférence, selon l'invention, on utilise un mélange Lipidique constitué d'au moins un lipide amphiphile et d'au moins un Lipide hydrophobe teL que stéroL, comme le cholestérol ou le β- sitosteroL. La quantité, exprimée en mole, de Lipide hydrophobe ne doit généralement pas être supérieure à la quantité de lipide amphiphiLe, et de préférence elle ne doit pas être supérieure à 0,5 fois cette quantité.Preferably, according to the invention, a lipid mixture is used which consists of at least one amphiphilic lipid and at least one hydrophobic lipid such as steroid, such as cholesterol or β-sitosteroL. The amount, expressed in moles, of hydrophobic lipid should generally not be greater than the amount of amphiphilic lipid, and preferably it should not be greater than 0.5 times this amount.
L'incorporation en des phases Lamellaires lipidiques hydratées ou dans des Liposomes, des composés ou des extraits con¬ tenant ces composés, utilisés conformément à la présente invention, peut être réalisée selon des techniques de préparation connues, décrites par exemple dans Le document EP-B1-0 087 993 = US-A-4 508 703, éventuellement en combinaison avec le document EP-B1-0 107559 = US-A-4 621 023. D'autres buts, caractéristiques et avantages de l'invention apparaîtront clairement à La Lumière de La description explicative qui va suivre faite en référence à plusieurs exemples donnés simplement à titre d'illustration. En effet, la présente invention n'est nullement Limitée aux modes de réalisation décrits et illustrés. C'est ainsi, par exemple, qu'elle couvre également une composition cosmétique ou dermatologique destinée à prévenir ou ralentir le blanchiment des sourci Ls ou des cils. Dans les exemples, les pourcentages sont donnés en poids, sauf indication contraire.The incorporation into hydrated lipidic Lamellar phases or into Liposomes, compounds or extracts containing these compounds, used in accordance with the present invention, can be carried out according to known preparation techniques, described for example in document EP- B1-0 087 993 = US-A-4 508 703, possibly in combination with document EP-B1-0 107559 = US-A-4 621 023. Other objects, characteristics and advantages of the invention will appear clearly in the light of the explanatory description which will follow made with reference to several examples given simply by way of illustration. In fact, the present invention is in no way limited to the embodiments described and illustrated. It is thus, for example, that it also covers a cosmetic or dermatological composition intended to prevent or slow down the whitening of the sourced Ls or eyelashes. In the examples, the percentages are given by weight, unless otherwise indicated.
EXEMPLE 1EXAMPLE 1
Obtention d'un extrait méthanolique de ballote On traite à reflux pendant 3 h 500 g de parties aériennes de Ballota nigra composées essentiellement de tiges et de feuilles, avec 5 l environ de méthanol.Obtaining a Methanolic Bale Extract 500 g of aerial parts of Ballota nigra composed essentially of stems and leaves are treated at reflux for 3 hours, with approximately 5 l of methanol.
On filtre les extraits méthanoliques et on évapore Le filtrat sous pression réduite, puis on Lyophilise. On obtient ainsi l'extrait méthanolique de Ballota nigra appelé extrait I...The methanolic extracts are filtered and the filtrate is evaporated under reduced pressure, then lyophilized. This gives the methanolic extract of Ballota nigra called extract I ...
EXEMPLE 2EXAMPLE 2
Obtention d'un extrait à l'acétate d'éthyle de balloteObtaining an extract of ethyl acetate from bundles
En opérant comme décrit à L'exemple 1, mais en utilisant comme solvant de l'acétate d'éthyle, on obtient un extrait d'acé¬ tate d'éthyle de Ballota nigra dénommé extrait _2-By operating as described in Example 1, but using ethyl acetate as solvent, an ethyl acetate extract from Ballota nigra called extract _ 2 is obtained.
EXEMPLE 3EXAMPLE 3
Incorporation d'un extrait de plantes entières de ballote dans des phases Lamellaires lipidiques hydratées ou dans des liposomesIncorporation of an extract of whole bale plants in hydrated lipidic Lamellar phases or in liposomes
Un extrait de plantes entières de Ballota nigra obtenu en opérant comme décrit à l'exemple 1, mais en utilisant les plantes entières, dénommé extrait I,, est incorporé dans des phases lamel¬ laires lipidiques hydratées ou dans des Liposomes selon La technique de préparation suivante : on pesé :An extract of whole plants of Ballota nigra obtained by operating as described in Example 1, but using whole plants, called extract I, is incorporated into hydrated lipid lip phases or in Liposomes according to the preparation technique. next : we weighed:
- lécîthîne de soja : 1,8 g- soy lecithin: 1.8 g
- β-sîtostéroL : 0,2 g- β-sosterosterol: 0.2 g
- extrait de Ballota nigra lyophilisé I, : 0,03 g- lyophilized Ballota nigra extract I,: 0.03 g
Ces constituants sont dissous dans un mélange constitué de 25 ml de dichlorométhane et 10 ml de méthanol.These constituents are dissolved in a mixture consisting of 25 ml of dichloromethane and 10 ml of methanol.
On évapore Le mélange ainsi obtenu dans un ballon rotatif à température de 60 C sous pression réduite.The mixture thus obtained is evaporated in a rotary flask at a temperature of 60 ° C. under reduced pressure.
Le film lipidique ainsi obtenu est alors repris et dis¬ persé sous agitation dans de l'eau distillée qsp 50 g, à tempéra¬ ture ambiante pendant 12 h.The lipid film thus obtained is then taken up and dispersed with stirring in distilled water qs 50 g, at room temperature for 12 h.
La suspension de vésicules lipidiques obtenue est ensuite homogénéisée par un traitement aux ultrasons pendant 10 min à 4 C, sous puissance de 150 W.The suspension of lipid vesicles obtained is then homogenized by ultrasonic treatment for 10 min at 4 ° C., at a power of 150 W.
La taille moyenne des liposomes ainsi obtenus est d'environ 140 nm.The average size of the liposomes thus obtained is approximately 140 nm.
Selon une variante de réalisation avantageuse, on gélifie ensuite cette suspension en la mélangeant à 50 g de gel de (S) CarbopoL ^940 à 1,25 % préparé séparément de façon classique. On obtient ainsi 100 g environ d'une suspension gélifiée de liposomes encapsulant, au moins partiellement, l'extrait de ballote, dont La concentration est d'environ 0,030 % par rapport au poids total de La suspension.According to an advantageous alternative embodiment, this suspension is then gelled by mixing it with 50 g of (S) CarbopoL ^ 940 gel at 1.25% prepared separately in a conventional manner. This gives approximately 100 g of a gelled suspension of liposomes encapsulating, at least partially, the bundle extract, the concentration of which is approximately 0.030% relative to the total weight of the suspension.
Ce gel est appelé "composition I " et peut être utilisé tel quel dans Le cadre de L'invention.This gel is called "composition I" and can be used as it is in the context of the invention.
EXEMPLE 4 Mesure de L'efficacité d'extraits de ballote selon L'invention sur des méLanocytes en cultureEXAMPLE 4 Measurement of the Efficiency of Baleot Extracts According to the Invention on Melanocytes in Culture
Protocole :Protocol:
Des méLanocytes murins S91 ensemencés à raison deMurine S91 melanocytes seeded at a rate of
10 cellules par boîte sont cultivés dans du milieu EMEM complé- mente en acides aminés non essentiels et contenant également 1 % de sérum de veau foetal et 0,08 μg/ml de Mitomycine C. 24 h après L'ensemencement, Le milieu de culture est remplacé par du milieu frais sans Mitomycine C, comprenant uniquement du milieu EMEM co plémenté, 1 % de sérum de veau foetal et, le cas échéant, Le produit à tester solubilisé dans du DMS0, à La concentration d'environ 40 mg/ml.10 cells per dish are cultured in EMEM medium supplemented with nonessential amino acids and also containing 1% of fetal calf serum and 0.08 μg / ml of Mitomycin C. 24 h after sowing, The culture medium is replaced by fresh medium without Mitomycin C, comprising only EMEM medium which is supplemented, 1% calf serum fetal and, where appropriate, the product to be tested dissolved in DMS0, at a concentration of approximately 40 mg / ml.
Six jours après ensemencement, on prélève les cellules que l'on isole par centrifugation et on récupère Le cuLot cellu¬ laire que l'on dissout dans de la soude 0,5 N, en proportion suffi- santé pour obtenir essentiellement la même concentration en poids de cellules par millilitre de solution finale.Six days after inoculation, the cells are removed which are isolated by centrifugation and the cell is recovered. This cell is dissolved in 0.5 N sodium hydroxide, in sufficient proportion to obtain essentially the same concentration in weight of cells per milliliter of final solution.
On procède à la lecture de La densité optique de La solu¬ tion obtenue sur un spectrophotomètre à 405 nm, ce qui permet d'évaluer La quantité de mélanine formée par comparaison à la den- site optique d'une solution de mélanine de concentration connue.The optical density of the solution obtained is read on a spectrophotometer at 405 nm, which makes it possible to evaluate the amount of melanin formed by comparison with the optical density of a melanin solution of known concentration. .
On procède également au comptage des cellules, et on calcule la quantité de mélanine formée pour 10 cellules.The cells are also counted, and the amount of melanin formed per 10 cells is calculated.
Les extraits I- et I-, de Ballota nigra ont été testés, à diverses concentrations en microgrammes (μg) par millilitre, ce qui est également mentionné aux tableaux I et II ci-après.The extracts I- and I-, of Ballota nigra were tested, at various concentrations in micrograms (μg) per milliliter, which is also mentioned in Tables I and II below.
Par ailleurs, il a été vérifié par un test équivalent que les méLanocytes utilisés dans les présents essais répondaient positivement à la bêta-MSH (Melanocyte-Stimulating Hormone).Furthermore, it has been verified by an equivalent test that the melanocytes used in the present tests responded positively to beta-MSH (Melanocyte-Stimulating Hormone).
L'efficacité E des produits testés sur la stimuLation de la mélanogénèse est calculée par la formule suivante :The efficiency E of the products tested on the stimulation of melanogenesis is calculated by the following formula:
q - q P oq - q P o
E = x 100 o dans laquelle les grandeurs q représentent les quantités de mélanine formée pour 10 cellules : q : culture recevant le produit à tester p q : culture témoin ne recevant aucun produit. Ό L'efficacité E des extraits testés à différentes concen¬ trations, calculée selon La formule ci-dessus, respectivement avec : a) L'extrait I1 de L'exemple 1 figure au tableau I ci- après, ou b) avec l'extrait I? de L'exemple 2 figure au tableau II ci-après.E = x 100 o in which the quantities q represent the quantities of melanin formed for 10 cells: q: culture receiving the product to be tested p q: control culture receiving no product. Ό The efficiency E of the extracts tested at different concentrations, calculated according to the above formula, respectively with: a) The extract I 1 of Example 1 is shown in Table I below, or b) with the extract I ? of Example 2 is shown in Table II below.
Les essais ayant été effectués avec trois boîtes par con¬ centration et par produit. Les valeurs figurant aux tableaux I et II relatives au nombre de cellules par boîte et à la quantité de mélanines exprimée en microgrammes Cμg) Cpour 10 cellules), sont des valeurs moyennes.The tests having been carried out with three boxes by concentration and by product. The values appearing in Tables I and II relating to the number of cells per dish and to the quantity of melanins expressed in micrograms Cμg) C for 10 cells ) , are average values.
L'étude statistique par Le test t de Student compare Les résultats entre les cultures témoin et les cultures traitées par Les produits selon l'invention.The statistical study by Student's t test compares the results between the control cultures and the cultures treated with the products according to the invention.
S = significatif à 5 %,S = significant at 5%,
NS = non significatif à 5 %.NS = not significant at 5%.
TABLEAU ITABLE I
Test avec l'extrait I1 de Ballota nigra Cparties aériennes)Test with extract I 1 from Ballota nigra Aerial parts)
TABLEAU II TABLE II
Test avec L'extrait I, de Ballota nigra (parties aériennes)Test with Extract I, from Ballota nigra (aerial parts)
II résulte à partir des tableaux I et II ci-dessus que les extraits selon l'invention stimulent, à des doses non cyto- toxiques, la production de mélanine dans une proportion significa¬ tive, ce qui représente un résultat tout à fait inattendu pour un homme de l'art. Par ailleurs, il a été également mis en évidence que Les extraits de ballote selon L'invention favorisent la différenciation élanocytaires par formation, au sein des méLanocytes, d'un plus grand nombre de melanosomes matures, transférables aux kératino- cytes.It follows from Tables I and II above that the extracts according to the invention stimulate, at non-cytotoxic doses, the production of melanin in a significant proportion, which represents a completely unexpected result for a man of art. Furthermore, it has also been demonstrated that the bundle extracts according to the invention promote the elanocyte differentiation by the formation, within melanocytes, of a greater number of mature melanosomes, transferable to keratinocytes.
EXEMPLE 5EXAMPLE 5
Mise en évidence de l'activité des produits de l'invention sur la différenciation des méLanocytes en cultureDemonstration of the Activity of the Products of the Invention on the Differentiation of Melanocytes in Culture
IL est connu que le processus de pigmentation de l'épi- derme cutané implique la différenciation des méLanocytes situés dans la couche basale de l'épiderme. Au cours de cette différen¬ ciation, on distingue généralement quatre stades (I à IV) corres¬ pondant à l'accumulation du pigment, c'est-à-dire La mélanine, au sein des melanosomes (organites cellulaires de stockage et de transfert de la mélanine). Le stade IV (Le plus coloré) est le stade final de chargement en pigment des melanosomes, que l'on considère de ce fait comme étant matures. On sait également que c'est à ce stade que la mélanine contenue dans les melanosomes est transférée aux kératinocytes situés à un niveau supérieur de l'épi- derme, au travers des prolongements dendritiques des méLanocytes.It is known that the pigmentation process of the cutaneous epidermis involves the differentiation of the melanocytes located in the basal layer of the epidermis. During this differentiation, there are generally four stages (I to IV) corresponding to the accumulation of the pigment, that is to say melanin, within the melanosomes (cellular organelles for storage and transfer melanin). Stage IV (The most colorful) is the final stage of pigment loading of the melanosomes, which we therefore considers it to be mature. It is also known that it is at this stage that the melanin contained in the melanosomes is transferred to the keratinocytes situated at a higher level of the epidermis, through dendritic extensions of the melanocytes.
Description de l'essai :Description of the test:
Des méLanocytes humains normaux isolés classiquement d'un lifting de femme de 50 ans, sont mis en culture au jour J=0, dans du milieu M 199 CGIBCO) complet, comprenant 10 % V/V de sérum de veau foetal et supplémenté en facteurs de croissance classiques.Normal human melanocytes conventionally isolated from a facelift from a 50 year old woman, are cultured on day D = 0, in medium M 199 CGIBCO) complete, comprising 10% V / V of fetal calf serum and supplemented with factors growth charts.
Au jour J=3, on ajoute dans Le milieu de culture 10 μg/ml de l'extrait de ballote I? (à l'acétate d'éthyle) de l'exemple 2, solubiLisé dans du DMS0.On day D = 3, 10 μg / ml of bundle extract I is added to the culture medium ? (with ethyl acetate) of example 2, solubilized in DMS0.
Au joi" J=6, le milieu est renouvelé par un milieu de composition idem que, contenant égaLement 10 μg/ml de L'extrait 'At day "J = 6, the medium is renewed with a medium of the same composition, also containing 10 μg / ml of the extract '
Au jour J=9, Les cellules sont incluses dans de la résine EP0N Cdi et tri-glycidyléther de glycérol), disponible chezOn day D = 9, the cells are included in EP0N resin Cdi and glycerol tri-glycidyl ether), available from
LADD, Vermont . USA. Les blocs de résine sont ensuite coupés en coupes ultrafines au moyen d'un microtome. L'ultrastructure des cellules peut ainsi être observée en microscopîe électronique à transmission.LADD, Vermont . USA. The resin blocks are then cut into ultrafine sections using a microtome. The ultrastructure of the cells can thus be observed by transmission electron microscopy.
Parallèlement, une culture témoin de méLanocytes a été réalisée à partir de la même source et dans Les mêmes conditions, si ce n'est qu'à partir du jour J=3, aucun extrait n'a été ajouté à la culture, seul du DMS0 a été ajouté à la même concentration, soit à 0,1 % en volume.At the same time, a control culture of melanocytes was carried out from the same source and under the same conditions, except that from day D = 3, no extract was added to the culture, only DMS0 was added at the same concentration, ie 0.1% by volume.
L'observation en mîcroscopie électronique montre que La culture témoin présente principalement des melanosomes de stades I et II. De plus, au niveau des méLanocytes, le système rétîculo- endothélial et l'appareil de Golgi apparaissent peu actifs.Observation by electronic microscopy shows that the control culture mainly presents stage I and II melanosomes. In addition, at the level of the melanocytes, the reticuloendothelial system and the Golgi apparatus appear to be not very active.
Par contre, La culture traitée présente de nombreux mela¬ nosomes parvenus aux stades III et IV, dans la majorité des cellules. Le système réticulo'endothélial et l'appareil de Golgi des cellules, au niveau desquels se produit la synthèsse de la tyro- sinase, sa glycosylation et la formation des vésicules de sécrétion de la mélanine, sont très développés, et donc très actifs. L'ensemble de ces caractéristiques traduit l'existence de méLano¬ cytes différenciés, notamment dans La mesure où ils possèdent de nombreux melanosomes matures, aux stades III et IV. Ainsi, la mise en évidence d'un mécanisme d'action des extraits de ballote permet, d'une part, d'expliquer L'activité des compositions selon l'invention favorisant La pigmentation cutanée, et d'autre part, autorise la mise en oeuvre d'un procédé pour obtenir en culture des méLanocytes plus différenciés avec des méla- nosomes de maturité élevée, ces méLanocytes pouvant être ensuite utilisés dans des greffes pour traiter certains troubles de La pigmentation, tels que le vitiligo.On the other hand, the culture treated presents numerous mela¬ nosomes having reached stages III and IV, in the majority of the cells. The reticuloendothelial system and endothelial cells Golgi apparatus, at which occurs the synthèsse of tyro- Sinase, its glycosylation and the formation of secretory vesicles melanin, are very developed, and therefore very active. All these characteristics reflects the existence of Melano ¬ cytes differentiated, particularly in the extent that they have many mature melanosomes, in stages III and IV. Thus, the demonstration of a mechanism of action of bundle extracts makes it possible, on the one hand, to explain the activity of the compositions according to the invention promoting skin pigmentation, and on the other hand, authorizes the setting implementation of a process for obtaining, in culture, more differentiated melanocytes with melanomas of high maturity, these melanocytes can then be used in grafts to treat certain pigmentation disorders, such as vitiligo.
EXEMPLE 6 Mise en évidence de l'activité inhibitrice des produits de l'inven¬ tion vis-à-vis de l'accumulation des triglycérides dans les adi¬ pocytesExample 6 Demonstration of the inhibitory activity of the products of the Inventory ¬ vis-à-vis the accumulation of triglycerides in adi¬ pocytes
Les triglycérides, qui constituent une réserve énergé¬ tique importante de l'organisme, sont formés à partir du glycérol et d'acides gras, dans la paroi intestinale, le foie et les tissus adipeux.Triglycerides, which constitute an important energy reserve for the body, are formed from glycerol and fatty acids, in the intestinal wall, the liver and adipose tissues.
Ainsi, les surchages graisseuses de l'organisme sont liées directement à l'accumulation de triglycérides dans Les adipo¬ cytes. Par ailleurs, il est connu que certaines Lignées de fibroblastes en culture, en particulier la lignée 3T3-L1 , sont capables de se différencier en adipocytes lorsque les conditions de culture sont permissives (par exemple selon la technique décrite par Teruo Kawada et al., dans Comp. Biochem. Physiol. (1990) vol. 96A, N.2, pp. 323-326).Thus, the fatty deposits of the organism are directly linked to the accumulation of triglycerides in adipocytes. Furthermore, it is known that certain fibroblast lines in culture, in particular the 3T3-L1 line, are capable of differentiating into adipocytes when the culture conditions are permissive (for example according to the technique described by Teruo Kawada et al., in Comp. Biochem. Physiol. (1990) vol. 96A, N.2, pp. 323-326).
Ainsi, pour mettre en évidence L'activité inhibitrice des produits de l'invention sur L'accumulation de triglycérides dans les adipocytes, une culture de cette lignée a été réalisée dans des conditions permettant leur différenciation en adipocytes, en pré-Thus, to demonstrate the inhibitory activity of the products of the invention on the accumulation of triglycerides in adipocytes, a culture of this line was carried out under conditions allowing their differentiation into adipocytes, in pre-
1 L sence de glucose marqué C, et en présence ou non de produit selon l' invention. Le gLycérol utilisé par les cellules pour la synthèse des triglycérides provient indirectement de La glycolyse du glucose. Ainsi, dans les conditions du test réalisé, il suffira de mesurer La radioactivité des triglycérides extraits à la fin de l'expé- rience, pour apprécier L'accumulation des triglycérides par Les adipocytes.1 The presence of glucose marked C, and whether or not in the presence of the product according to the invention. The glycerol used by cells for the synthesis of triglycerides comes indirectly from the glycolysis of glucose. Thus, under the conditions of the test carried out, it will suffice to measure the radioactivity of the triglycerides extracted at the end of the experiment, to assess the accumulation of triglycerides by adipocytes.
Au jour J=0, on ensemence par 2 x 10 cellules/boîte de la lignée 3T3-L1 (disponibles chez ATCC, référence CCL 92-1), des boîtes de Pétri de diamètre 35 mm contenant 2 ml de milieu de cul- ture constitué de milieu EMEM complet contenant 10 % V/V de sérum de veau foetal.On day D = 0, 2 × 10 cells / dish of the line 3T3-L1 (available from ATCC, reference CCL 92-1) are inoculated with 35 mm diameter petri dishes containing 2 ml of culture medium. consisting of complete EMEM medium containing 10% V / V of fetal calf serum.
Au jour J=1, le milieu de culture est remplacé par celui utilisé au jour J=0, auquel on a ajouté Les agents de différencia¬ tion, à savoir 100 μg/ml d'isobutylméthylxanthine CIBMX) etOn day D = 1, the culture medium is replaced by that used on day D = 0, to which the differentiation agents have been added, namely 100 μg / ml of isobutylmethylxanthine CIBMX) and
14 0,1 μg/ml de dexaméthasone, de la mitomycîne-C et du C-glucose à14 0.1 μg / ml dexamethasone, mitomycin-C and C-glucose at
La concentration de 0,5 μCi/ml. De plus, ce milieu de culture con¬ tient Les produits à tester, à l'exception du milieu correspondant aux cultures témoins.The concentration of 0.5 μCi / ml. In addition, this culture medium contains the products to be tested, with the exception of the medium corresponding to the control cultures.
Au jour J=7, on extrait par de L'heptane Les triglycé- rides présents dans les cultures. Pour cela, les cellules en cul¬ ture sont d'abord décallées de leur boîte, de façon classique au moyen d'une solution de trypsîne. La suspension cellulaire ainsi obtenue est alors lysée par addition d'une quantité suffisante de réactif de Dole CDole V.P. et al., Journal of Biological Chemistry C1960) vol. 235, N.9, pp. 2595). On ajoute ensuite de L'eau, puis de l'heptane à La préparation, ce qui permet d'obtenir deux phases : l'une aqueuse et l'autre organique constituée d'heptane. Cette dernière, contenant les triglycérides présents dans la cul¬ ture, est alors collectée, et sa radioactivité est déterminée en scintillation liquide, par exemple au moyen d'un appareil du type 0NTR0N BETA V®.On day D = 7, the triglycerides present in the cultures are extracted with heptane. For this, the cells in culture are first removed from their box, in a conventional manner using a solution of trypsin. The cell suspension thus obtained is then lysed by adding a sufficient amount of Dole CDole reagent V.P. et al., Journal of Biological Chemistry C1960) vol. 235, N.9, pp. 2595). Water is then added, then heptane to the preparation, which makes it possible to obtain two phases: one aqueous and the other organic consisting of heptane. The latter, containing the triglycerides present in the culture, is then collected, and its radioactivity is determined in liquid scintillation, for example by means of a device of the 0NTR0N BETA V® type.
La mesure de la radioactivité des extraits obtenus à partir des cultures contenant le produit de l'invention, comparée à celle des cultures témoins, permet donc d'évaluer L'inhibition de l'accumulation des triglycérides, ceux-ci étant formés à partir du glucose radioactif non extrait par l'heptane. Ainsi, on calcule l'activité A des produits de L'inven¬ tion selon la formule suivante :Measuring the radioactivity of the extracts obtained from the cultures containing the product of the invention, compared with that of the control cultures, therefore makes it possible to evaluate the inhibition of the accumulation of triglycerides, these being formed from radioactive glucose not extracted by heptane. Thus, the activity A of the products of the invention is calculated according to the following formula:
FL - RFL - R
A = x 100A = x 100
R représentant la radioactivité des extraits de triglycérides des cultures témoins, exprimées en cpm (coups par minute), et R représentant celle des cultures en présence du produit selon l'invention, exprimée également en cpm.R representing the radioactivity of the triglyceride extracts of the control cultures, expressed in cpm (counts per minute), and R representing that of the cultures in the presence of the product according to the invention, also expressed in cpm.
Le produit de l'invention ayant fait l'objet du présent essai est constitué par l'extrait méthanolique I. de ballote, obtenu selon l'exemple 1.The product of the invention which was the subject of this test consists of the methanolic extract I. of bundle, obtained according to Example 1.
Le tableau III ci-après présente Les résultats de L'acti¬ vité inhibitrice de l'extrait I. à deux valeurs différentes de concentration dans les cultures.Table III below presents the results of the inhibitory activity of extract I. at two different concentration values in the cultures.
TABLEAU IIITABLE III
La significativité des résultats a été calculée par Le test t de Student, avec p < 0,05.The significance of the results was calculated by Student's t test, with p <0.05.
IL apparaît clairement à la Lecture de ce tableau que La présence de l'extrait I. selon l'invention inhibe significativement de manière importante l'accumulation de triglycérides dans Les adi¬ pocytes en culture.It is clear from reading this table that the presence of extract I. according to the invention significantly significantly inhibits the accumulation of triglycerides in adi¬ cells in culture.
Ainsi, les produits de L'invention peuvent être utilisés avantageusement comme principe actif dans des compositions cosmé- tiques ou pharmaceutiques, notamment dermatologiques, en vue de la prévention ou du traitement des surcharges graisseuses, en parti¬ culier de La cellulite.Thus, the products of the invention can be advantageously used as active principle in cosmetic compositions. ticks or pharmaceuticals, especially dermatological, for the prevention or treatment of fatty overloads, in particular ¬ Cellulite.
On donnera ci-après divers exemples de formulation de compositions cosmétique ou pharmaceutique, notamment dermatolo¬ gique.Various examples of the formulation of cosmetic or pharmaceutical compositions, especially dermatological compositions, will be given below.
EXEMPLE 7EXAMPLE 7
Loti_.:_ favorisant la pigmentation des cheveuxLoti_.:_ promoting pigmentation of hair
- extrait I. (exemple 1) 0,15 g- extract I. (example 1) 0.15 g
- propylèneglycol 5 g- propylene glycol 5 g
- Crémophor RH40®. 1 g- Crémophor RH40®. 1 g
- éthanol 30 g - excipient aqueux parfumé qsp 100 g- ethanol 30 g - scented aqueous excipient qs 100 g
Appliquer la lotion sur Les cheveux à raison de 1 ml deux fois par jour pendant 6 mois pour L'obtention d'un effet de pigmen¬ tation significatif.Apply the lotion to the hair at the rate of 1 ml twice a day for 6 months to obtain a significant pigmen¬ tation effect.
EXEMPLE 8EXAMPLE 8
Gel favorisant Le bronzageTanning promoting gel
La préparation du gel est réalisée à partir de deux phases, respectivement A et B, suivantes :The preparation of the gel is carried out from two phases, respectively A and B, as follows:
1) Phase A1) Phase A
- extrait I-, Cexemple 2) 0,1 g- extract I-, Example 2) 0.1 g
- maLyltyrosine 2 g - propylèneglycol 4 g- maLyltyrosine 2 g - propylene glycol 4 g
- glycérol 0,5 g- glycerol 0.5 g
- crémophor RH40^ 1 g- crémophor RH40 ^ 1 g
- éthanol 25 g- ethanol 25 g
- excipient aqueux parfumé qsp 50 g 2) Phase B gel de Carbopol 940 R à 1,25 % 50 g- scented aqueous excipient qs 50 g 2) Phase B Carbopol 940 R gel at 1.25% 50 g
On ajoute progressivement la phase A dans La phase B et on mélange avec un agitateur à hélice jusqu'à dispersion complète. On obtient ainsi un gel favorisant Le bronzage de la peau, qui peut être appliqué avant ou pendant L'exposition solaire.Phase A is gradually added to Phase B and mixed with a propeller stirrer until completely dispersed. A gel promoting the tanning of the skin is thus obtained, which can be applied before or during sun exposure.
EXEMPLE 9 Composition amincissanteEXAMPLE 9 Slimming composition
- extrait de ballote selon l'invention (exemple 1) 0,1 g- bundle extract according to the invention (example 1) 0.1 g
- alcool à 96 % 32 g- 96% alcohol 32 g
(R>(R>
- Carbopol 941 2,5 g - excipient aqueux avec conservateur q.s.p. 100 g- Carbopol 941 2.5 g - aqueous excipient with preservative q.s.p. 100g
On dissout tout d'abord l'extrait de ballote dans l'alcool, puis le tout est incorporé à un excipient gélifié conte¬ nant le Carbopol. On obtient ainsi une composition amincissante qui peut être appliquée sur les zones à traiter. The ballot extract is first dissolved in alcohol, then the whole is incorporated into a gelled excipient containing the Carbopol. A slimming composition is thus obtained which can be applied to the areas to be treated.

Claims

REVENDICATIONS
1. Composition cosmétique ou pharmaceutique, notamment dermatologique, destinée en particulier à favoriser la pigmentation de La peau, à prévenir ou ralentir l'apparition des chev ux blancs ; à réduire La quantité de triglycérides dans les adipo¬ cytes, à éviter le développement d'accumulations graisseuses dans L'organisme, telle que La cellulite, caractérisée en ce qu'elle comprend à titre d'ingrédient actif une quantité cosmétiquement ou pharmaceutiquement efficace d'un extrait de ballote éventuellement dans un excipient cosmétiquement ou pharmaceutiquement acceptable.1. Cosmetic or pharmaceutical composition, in particular dermatological composition, intended in particular to promote the pigmentation of the skin, to prevent or slow down the appearance of white hair; reduce the amount of triglycerides in adipo¬ cytes, avoid the development of fatty accumulations in the body, such as cellulite, characterized in that it comprises as active ingredient a cosmetically or pharmaceutically effective amount d 'an extract of bundle optionally in a cosmetically or pharmaceutically acceptable excipient.
2. Composition selon la revendication 1, caractérisée en ce que l'extrait de ballote est choisi parmi les extraits de Ballota nigra, de BalLota lanata et de Ballota suavelens. 2. Composition according to claim 1, characterized in that the ballote extract is chosen from the extracts of Ballota nigra, BalLota lanata and Ballota suavelens.
3. Composition selon La revendication 1 ou 2, caracté¬ risée en ce que l'extrait de ballote est choisi parmi un extrait de la plante entière, et un extrait des parties aériennes, en parti¬ culier essentiellement des tiges et des feuilles.3. Composition according to claim 1 or 2, caracté¬ ized in that the bale extract is chosen from an extract of the whole plant, and an extract from the aerial parts, in particu¬ larly mainly stems and leaves.
4. Composition selon L'une des revendications 1 à 3, caractérisée en ce que L'extrait de ballote précité est un extrait avantageusement obtenu par un procédé comprenant au moins une étape d'extraction avec par exemple un solvant choisi parmi le groupe constitué par L'eau, les alcools comportant de préférence de 1 à 4 atomes de carbone, tels que Le méthanoL, l'éthanol ou Le pro- panoL, un mélange hydroalcooLique de ces alcools, les solvants chlorés comprenant 1 ou 2 atomes de carbone, tels que le chloro¬ forme ou le dichlorométhane, Les esters organiques comportant de préférence 3 à 6 atomes de carbone, tels que l'acétate d'éthyle.4. Composition according to one of claims 1 to 3, characterized in that The above-mentioned bundle extract is an extract advantageously obtained by a process comprising at least one extraction step with, for example, a solvent chosen from the group consisting of Water, alcohols preferably containing from 1 to 4 carbon atoms, such as methanoL, ethanol or propanol, a hydroalcoholic mixture of these alcohols, chlorinated solvents comprising 1 or 2 carbon atoms, such as chloro¬ form or dichloromethane, organic esters preferably comprising 3 to 6 carbon atoms, such as ethyl acetate.
5. Composition selon L'une des revendications 1 à 4, caractérisée en ce que la concentration en extrait de ballote pré¬ cité, exprimée en poids sec, est comprise entre 0,0001 % et 5 % en poids, de préférence entre 0,01 % et 0,5 % en poids, par rapport au poids total de La composition.5. Composition according to one of claims 1 to 4, characterized in that the concentration of above-mentioned bundle extract, expressed in dry weight, is between 0.0001% and 5% by weight, preferably between 0, 01% and 0.5% by weight, relative to the total weight of the composition.
6. Composition selon L'une des revendications précé- dentés, destinée plus particulièrement à La pigmentation de la peau ou des cheveux, caractérisée en ce que La composition contient en outre une xanthine, en particulier La 1-méthylxanthine, La 3- méthylxanthine, la 3-isobutyLméthyLxanthine ou La théophyl Line, de préférence à une concentration pondérale comprise entre 0,001 % et 2%, et encore de préférence comprise entre 0,01% et 0,5%, par rap- port au poids total de la composition.6. Composition according to one of the preceding claims, intended more particularly for pigmentation of the skin or hair, characterized in that the composition contains in addition to a xanthine, in particular 1-methylxanthine, 3-methylxanthine, 3-isobutyLmethyLxanthine or Theophyl Line, preferably at a concentration by weight of between 0.001% and 2%, and more preferably between 0.01% and 0.5%, based on the total weight of the composition.
7. Composition selon L'une des revendications précé¬ dentes, en particulier pour favoriser la pigmentation de la peau ou des cheveux, caractérisée en ce que la composition contient en outre de la tyrosine ou l'un de ses dérivés tels que le tyrosinate de glucose, la N-malyltyrosine, de préférence à une concentration pondérale comprise entre 0,001% et 10%, par rapport au poids total de la composition.7. Composition according to one of the preceding claims, in particular for promoting the pigmentation of the skin or of the hair, characterized in that the composition also contains tyrosine or one of its derivatives such as tyrosinate. glucose, N-malyltyrosine, preferably at a concentration by weight of between 0.001% and 10%, relative to the total weight of the composition.
8. Composition selon L'une des revendications 1 à 7, caractérisée en ce qu'elle contient en outre au moins une autre substance active, à une concentration efficace, choisie parmi Les vitamines, en particulier les vitamines B, la quinine ou ses dérivés, les rubéfiants, tels que le nicotinate de méthyle, un surnageant de culture de fibroblastes de papille, des hydrolysats de kératine, des oligoéléments tels que zinc, sélénium, cuivre, des inhibiteurs de 5-α-réductase, tels que progestérone, cyproté- rone acétate, minoxidil, acide azélaîque et ses dérivés, 1,4- méthyl-4-azastéroïde, en particulier La 17-β-N, N-diéthyLcarba- moyl-4-méthyl-4-aza-5-α-androstan-3-one, ou encore un extrait de Serenoa repens. 8. Composition according to one of claims 1 to 7, characterized in that it also contains at least one other active substance, at an effective concentration, chosen from vitamins, in particular vitamins B, quinine or its derivatives , rubefiants, such as methyl nicotinate, a culture supernatant of papilla fibroblasts, keratin hydrolysates, trace elements such as zinc, selenium, copper, 5-α-reductase inhibitors, such as progesterone, cyprotein- rone acetate, minoxidil, azelaic acid and its derivatives, 1,4-methyl-4-azasteroid, in particular La 17-β-N, N-diethyLcarba- moyl-4-methyl-4-aza-5-α-androstan- 3-one, or an extract from Serenoa repens.
9. Composition selon l'une des revendications 1 à 8, caractérisée en ce qu'elle contient en outre au moins une substance active, à une concentration efficace, choisie parmi une xanthine, en particulier la caféine, un extrait de lierre (Hedera HeLLix), ou un extrait de Coleus, en particulier de Coleus forskohlii. 9. Composition according to one of claims 1 to 8, characterized in that it also contains at least one active substance, at an effective concentration, chosen from a xanthine, in particular caffeine, an ivy extract (Hedera HeLLix ), or an extract from Coleus, in particular from Coleus forskohlii.
10. Composition selon L'une des revendications précé¬ dentes, caractérisée en ce que, Lorsqu'elle est destinée à L'admi¬ nistration topique, ladite composition comprend un excipient particulier jouant le rôle de vecteur de pénétration, c'est-à-dire un agent favorisant la pénétration et la diffusion au niveau des structures cutanées concernées tel que ceux utilisés dans les domaines de la cosmétologie et de la dermo-pharmacie comme par exemple l'alcool éthylique, un glycol en particulier le glycérol ou Le propylèneglycol, L'acide oléique, le laurocapram ou une huile essentîellle notamment Le menthol ou l'eucalyptol.10. Composition according to one of the preceding claims, characterized in that, when it is intended for topical administration, said composition comprises a particular excipient playing the role of penetration vector, that is to say -to say an agent promoting the penetration and the diffusion at the level of the cutaneous structures concerned such as those used in the fields of cosmetology and dermo-pharmacy as for example ethyl alcohol, a glycol in particular glycerol or propylene glycol, oleic acid, laurocapram or an essential oil in particular menthol or eucalyptol.
11. Composition selon l'une des revendications précé- dentés, caractérisée en ce que Ladite composition est sous une forme destinée à L'administration superficielle sur la peau ou le cuir chevelu, en particulier sous forme de crème, de gel, de lait ou de lotion.11. Composition according to one of the preceding claims, characterized in that the said composition is in a form intended for surface administration on the skin or the scalp, in particular in the form of a cream, gel, milk or of lotion.
12. Composition selon L'une des revendications précé- dentés, caractérisée en ce qu'elle contient des phases lamellaires lipidiques hydratées ou des liposomes incorporant ou non l'extrait de Ballota nigra précité.12. Composition according to one of the preceding claims, characterized in that it contains hydrated lipidic lamellar phases or liposomes incorporating or not the abovementioned Ballota nigra extract.
13. Procédé de fabrication d'une composition cosmétique ou pharmaceutique, notamment dermatologique, destinée en particu- lier à favoriser la pigmentation de la peau, à prévenir ou ralentir L'apparition des cheveux blancs ; à traiter les désordres de la pigmentation de la peau ou des cheveux ; à réduire la quantité de triglycérides dans les adipocytes, à éviter Le développement d'accumulations graisseuses dans l'organisme, telles que la cellu- Lite, caractérisé en ce qu'il comprend l'incorporation d'au moins un extrait de ballote, en particulier tel que précédemment défini à La revendication 2 ou 3, dans un excipient, véhicule ou support cosmétiquement ou pharmaceutiquement acceptable.13. Process for manufacturing a cosmetic or pharmaceutical composition, in particular a dermatological composition, intended in particular to promote pigmentation of the skin, to prevent or slow down the appearance of white hair; to treat pigmentation disorders of the skin or hair; to reduce the amount of triglycerides in adipocytes, to avoid the development of fatty accumulations in the organism, such as cellu-Lite, characterized in that it comprises the incorporation of at least one extract of bundle, in particular as previously defined in claim 2 or 3, in a cosmetically or pharmaceutically acceptable excipient, vehicle or support.
14. Utilisation d'un extrait de ballote, en particulier tel que défini aux revendications 2 à 5, pour La préparation d'une composition cosmétique ou pharmaceutique, notamment dermatolo¬ gique, destinée en particulier à favoriser la pigmentation de la peau, à prévenir ou ralentir l'apparition des cheveux blancs ou à traiter les désordres de la pigmentation de la peau ou des cheveux ; à réduire La quantité de triglycérides dans les adipo¬ cytes, à éviter le développement d'accumulations graisseuses dans l'organisme, telles que la cellulite.14. Use of a bundle extract, in particular as defined in claims 2 to 5, for the preparation of a cosmetic or pharmaceutical composition, in particular dermatological, intended in particular to promote pigmentation of the skin, to prevent or to slow the appearance of white hair or to treat disorders of the pigmentation of the skin or hair; to reduce the amount of triglycerides in adipo¬ cytes, to avoid the development of fatty accumulations in the body, such as cellulite.
15. Procédé de traitement cosmétique ou thérapeutique d'une insuffisance ou de désordre de La pigmentation, caractérisé en ce qu'il comprend l'application d'une quantité efficace d'au moins un extrait de ballote, en particulier tel que défini aux revendications 2 à 5, éventuellement incorporé dans un excipient, véhicule ou support cosmétiquement ou pharmaceutiquement acceptable, de préférence sur les zones concernées de La peau ou du cuir chevelu d'un être humain, afin de rétablir une pigmentation normale de la peau ou des cheveux et/ou pour augmenter cette pig¬ mentation.15. Cosmetic or therapeutic treatment process for an insufficiency or disorder of pigmentation, characterized in that it comprises the application of an effective amount of at least one extract of bundle, in particular as defined in Claims 2 to 5, optionally incorporated in a cosmetically or pharmaceutically acceptable excipient, vehicle or support, preferably on the areas concerned of the skin or scalp of a human being, in order to restore normal pigmentation of the skin or hair and / or to increase the pig ¬ mentation.
16. Procédé de traitement de méLanocytes en culture, notamment de méLanocytes humains en culture, en vue de Leur faire acquérir des caractères de maturation convenables pour une utilisa- tion ultérieure, caractérisé en ce qu'il comprend la culture desdits méLanocytes dans un milieu de culture comprenant une quan¬ tité efficace d'au moins un extrait de ballote, en particulier tel que défini aux revendications 2 à 5, pendant une période de temps suffisante pour obtenir une différenciation des méLanocytes. 16. Process for the treatment of melanocytes in culture, in particular human melanocytes in culture, with a view to making them acquire maturing characters suitable for later use, characterized in that it comprises the culture of said melanocytes in a medium of culture comprising an effective quantity of at least one bundle extract, in particular as defined in claims 2 to 5, for a period of time sufficient to obtain a differentiation of the melanocytes.
17. Procédé de traitement cosmétique ou thérapeutique consistant en des greffes de méLanocytes chez un mammifère, de pré¬ férence chez l'homme, caractérisé en ce qu'on greffe des méLano¬ cytes, notamment des méLanocytes humains, qui ont subi une diffé¬ renciation par culture en présence d'une quantité efficace de dif- férenciation d'au moins un extrait de ballote, en particulier tel que défini aux revendications 2 à 5.17. Cosmetic or therapeutic treatment method consisting of grafts of melanocytes in a mammal, preferably in humans, characterized in that grafts of melanocytes, in particular human melanocytes, which have undergone diffe¬ renciation by culture in the presence of an effective amount of differentiation of at least one bundle extract, in particular as defined in claims 2 to 5.
18. Procédé de traitement cosmétique ou thérapeutique pour réduire la quantité de triglycérides dans Les adipocytes d'un mammifère, en particulier d'un être humain, caractérisé en ce qu'il comprend l'application à titre préventif ou curatif sur les zones à traiter, d'une quantité efficace pour réduire La quantité de tri¬ glycérides dans Les adipocytes en particulier pour inhiber leur synthèse par ces cellules, d'au moins un extrait de ballote, en particulier tel que défini aux revendications 2 à 5, éventuelle- ment incorporé dans un excipient, véhicule ou support cosméti¬ quement ou pharmaceutiquement acceptable.18. Cosmetic or therapeutic treatment method for reducing the amount of triglycerides in adipocytes of a mammal, in particular of a human being, characterized in that it comprises the application for preventive or curative purposes to the areas to be treated , an amount effective to reduce the amount of tri¬ glycerides in adipocytes, in particular to inhibit their synthesis by these cells, of at least one bundle extract, in particular as defined in claims 2 to 5, optionally incorporated in a cosmetically or pharmaceutically acceptable excipient, vehicle or support.
19. Procédé de prévention ou de traitement des surcharges graisseuses, en particulier de la cellulite, caractérisé en ce qu'il comprend l'application sur les zones du corps d'un mammifère, en particulier d'un être humain souffrant de surcharges graisseuses dans L'organisme, telles que la cellulite, d'une quantité efficace pour obtenir la réduction desdites surcharges graisseuses d'au moins un extrait de ballote, en particulier tel que défini aux revendications 2 à 5, éventuellement incorporé dans un excipient, véhicule ou support cosmétiquement ou pharmaceutiquement acceptable. 19. Method for preventing or treating fatty overloads, in particular cellulite, characterized in that it comprises application to the areas of the body of a mammal, in particular of a human being suffering from fatty overloads in the organism, such as cellulite, of an amount effective for obtaining the reduction of said fatty overloads of at least one bale extract, in particular as defined in claims 2 to 5, optionally incorporated in an excipient, vehicle or cosmetically or pharmaceutically acceptable carrier.
EP93901780A 1991-11-29 1992-11-27 Cosmetic or pharmaceutical composition containing a black horehound extract Ceased EP0618801A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9114849A FR2684300B1 (en) 1991-11-29 1991-11-29 COSMETIC OR PHARMACEUTICAL COMPOSITION, ESPECIALLY DERMATOLOGICAL, IN PARTICULAR FOR PROMOTING PIGMENTATION OF THE SKIN OR HAIR, CONTAINING A BALLOTE EXTRACT, AND ITS MANUFACTURING METHOD.
FR9114849 1991-11-29
PCT/FR1992/001105 WO1993010804A1 (en) 1991-11-29 1992-11-27 Cosmetic or pharmaceutical composition containing a black horehound extract

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Publication Number Publication Date
EP0618801A1 true EP0618801A1 (en) 1994-10-12

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EP (1) EP0618801A1 (en)
JP (1) JPH07501336A (en)
CA (1) CA2124555A1 (en)
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US5759524A (en) * 1996-02-09 1998-06-02 The Procter & Gamble Company Photoprotective compositions
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FR2684300A1 (en) 1993-06-04
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WO1993010804A1 (en) 1993-06-10
FR2684300B1 (en) 1994-03-11
US5591437A (en) 1997-01-07
US5514374A (en) 1996-05-07

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