Classifications

• • 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
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • 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
• • 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
  • A61Q5/12—Preparations containing hair conditioners
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q7/00—Preparations for affecting hair growth
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
  • A61K2800/92—Oral administration

Definitions

• the present invention relates to cosmetic treatment methods for preventing or reducing whitening of integuments, and the use of plant extracts as an agent for promoting pigmentation of integuments and / or for limiting and / or preventing depigmentation.
• plant extracts as an agent for promoting pigmentation of integuments and / or for limiting and / or preventing depigmentation.
• it relates to pomegranate extracts, or compositions containing them, for combating canities.
• the color of human hair and skin is a function of various factors including seasons of the year, race, sex and age. It is mainly determined by the concentration of melanin produced by melanocytes. Melanocytes are specialized cells that, via particular organelles, melanosomes, synthesize melanin. The synthesis of melanin or melanogenesis is complex and involves schematically the following main steps:
• Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductase EC 1 .14.18.1) is involved in this series of reactions by catalyzing, in particular, the conversion reaction of tyrosine to Dopa (dihydroxyphenylalanine). and the transformation reaction of Dopa into Dopaquinone.
• the upper part of the hair follicle presents itself as a tubular invagination of the epidermis which penetrates to the deep layers of the dermis.
• the lower part, or hairy bulb, itself contains an intussusception in which is the dermal papilla.
• the dermal papilla there is an area populated by cells with a high rate of proliferation (matrix cells) in the lower part of the bulb. These cells are the precursors of the keratinized cells that will constitute the hair. The cells that result from the proliferation of these precursors migrate vertically into the bulb and keratinize gradually in the upper part of the bulb, this set of keratinized cells will form the hair shaft.
• the color of hair and hair is partly based on the presence in varying amounts and ratios of two groups of melanins: eumelanins (brown and black pigments) and pheomelanines (red and yellow pigments).
• the pigmentation of the hair and hair requires the presence of melanocytes in the bulb of the hair follicle. These melanocytes are active, ie they synthesize melanins. This melanin is transmitted to the keratinocytes intended to form the hair shaft which will result in the growth of a hair, or a hair, pigmented. This structure is called "follicular unit of pigmentation".
• melanogenesis involves at least three enzymes: tyrosinase, DOPAchrome tautomerase (TRP-2) and DHICAoxidase (TRP-1).
• Tyrosinase is the enzyme that initiates the biosynthesis of melanins. It is also described as the enzyme limiting melanogenesis.
• Tyrosinase catalyzes the oxidation of tyrosine to Dopa and Dopaquinone. The Dopaquinone compound is spontaneously converted to Dopachrome, or cysteinyldopa derivatives in the presence of cysteine.
• TRP-2 catalyzes the tautomerization of Dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA).
• DHICA 5,6-dihydroxyindole-2-carboxylic acid
• DHI 5,6-dihydroxyindole
• TRP-1 oxidizes DHICA compounds to form quinone derivatives.
• the three tyrosinase enzymes, TRP-2 and TRP-1 appear specifically involved in eumelanogenesis. In addition, the activity of these three enzymes has been described as necessary for the maximal activity of biosynthesis of eumelanines.
• This cycle comprises a growth phase (anagen phase), a degeneration phase (catagen phase) and a rest phase (telogen phase) following which a new anagen phase will develop.
• the follicular unit of pigmentation must also be cyclically renewed.
• part of the inactive melanocytes contained in the telogen capsule proliferates is positioned around the dermal papilla of the incipient bulb, and begins to express the enzymes necessary for the synthesis of melanins such as tyrosinase and TRP-1, but not the TRP-2 enzyme ⁇ Pigment Cell Res 2004 Oct; 17: 488-497).
• the other part of quiescent melanocytes remains inactive in the upper region of the hair follicle.
• the tyrosinase and TRP-1 enzymes will be expressed in the hair bulb melanocytes throughout the anagen phase but will no longer be expressed in the melanocytes during the catagenic phase and the telogen phase.
• the normal cycle of melanocytes in the human hair follicle requires the presence of precursor melanocytes in the upper region of the hair follicle which will be cyclically activated to regenerate the follicular unit of pigmentation. It is known that in most populations the brown coloration of the skin and the maintenance of a constant color of the hair are important aspirations.
• compositions containing a phosphodiesterase inhibitor (WO9517161), DNA fragments (WO9501773), diacylglycerol (WO9404122), prostaglandins (WO951 1003) or pyrimidine 3-oxide derivatives (EP829260).
• WO 04/073594 proposes the use of inhibitors of the enzyme 15-PGDH.
• EP1870081 describes the use of ellagic acid or its derivatives for the treatment of canities.
• Pomegranate is a small fruit tree with deciduous foliage, native to Asia, particularly from the Middle East belonging to the family Punicaceae. It can reach about 5 m, but often it does not reach more than 1, 50 m.
• the flowers are red or orange or scarlet, single or double, depending on the variety.
• the fruits are edible and consumed since ancient times. Synonyms are Punica spinosa, Punica florida or Granatum puniceum. Its fruit is pomegranate, red-orange in color, with a hard and leathery pericarp (or bark) containing in 6 to 12 membranous compartments numerous triangular seeds with a translucent and juicy appearance. Pomegranate is rich in vitamins (B, C and D) and polyphenols in the form of tannins. Bark extracts have been proposed for their astringent, antibacterial and anti-haemorrhagic properties. Extracts rich in tannins, are used traditionally in theixie pharmacopoeia to blacken the hair, in topical application.
• Patent EP138419 describes the topical application of pomegranate extract to prolong the color intensity of colored hair.
• WO 2007/004229 discloses the use of oily fractions of pomegranate seeds to promote regeneration of the skin.
• FR 2730408 relates to compositions for depigmenting the skin by topical application, which may comprise extracts of various fruits, including that of Punica granatum.
• EP1523895 relates to compositions for the oral route containing a combination of an extract of Punica granatum, a fatty acid, in particular conjugated linoleic acid (CLA) and OPC.
• CLA conjugated linoleic acid
• OPC conjugated linoleic acid
• US6630163 describes compositions for the treatment of dermatological disorders containing fruit extracts, and in particular extracts of pomegranate.
• Punica granatum or its extracts orally, to prevent, limit or stop the progression of canities, and / or promote the natural re-pigmentation of dander, in particular hair and / or hair.
• the invention therefore particularly relates to the use of at least one plant of the species Punica granatum or of one of its extracts or a composition containing at least one such plant or one of its extracts in a physiologically acceptable medium, as an agent for promoting and / or inducing and / or stimulating the pigmentation of integuments, and / or as an agent for preventing and / or limiting depigmentation and / or whitening of integuments, especially as an agent for preventing and / or or limit canities; this agent is more particularly used in mammals, in particular in humans.
• the invention relates to the cosmetic use of at least one plant of the species Punica granatum or of one of its extracts in a composition adapted to the oral route for promoting and / or inducing and / or stimulating the pigmentation of integuments, and / or for preventing and / or limiting depigmentation and / or whitening of integuments and / or for preventing and / or limiting canities .
• the invention also relates to the use of at least one plant of the species Punica granatum or at least one of its extracts for the preparation of a composition intended to promote and / or induce and / or stimulate the pigmentation of integuments, and / or intended to prevent and / or limit the depigmentation and / or whitening of integuments and / or intended to prevent and / or limit canities.
• compositions which are useful according to the invention may contain a physiologically acceptable medium or excipients.
• skin By skin is meant the entire skin, including the scalp and mucous membranes.
• dander we mean all the integumentary appendages and in particular the nails, the hair and the hair.
• hair and hair is meant all the hairy appendages and in particular also the eyelashes and the eyebrows.
• At least one means one or two or more, including mixtures in all proportions of the various elements mentioned.
• the term “a” in this application shall be understood to mean at least one.
• the extract of Punica granatum useful according to the invention may be chosen from flower extracts, fruit extracts, seed extracts and bark extracts of Punica granatum, and mixtures thereof in all proportions.
• a fruit extract - or pomegranate extract - this extract can come from all parts of the pomegranate or more specifically from the bark and / or seeds.
• a total extract that is to say an extract comprising all parts of the pomegranate, from which the woody parts have been removed, can be used.
• use will be made of at least one extract enriched in certain fractions, in particular an extract titrated with polyphenols.
• the pomegranate extract can be obtained from any part of the pomegranate and in particular from the fruit including or not the seed, or especially from the bark of the fruit.
• extract is meant both a crude mixture of parts of the plant roughly reduced in pieces and the extraction solvent that fractions or more preparations or less elaborate active principles solubilized during extraction.
• a total extract can be used, that is to say an extract comprising all the fractions present in the parts of Punica granatum, possibly devoid of the cellulosic parts.
• use will be made of at least one extract enriched in certain fractions.
• the extract can be obtained by any method for preparing a plant extract known to those skilled in the art.
• the extract may be obtained by maceration of the part of the plant in water, or in a solvent composed of a mixture of water and an organic solvent, for example water-alcohol, or water- acetone, or water-propylene glycol, or water-butylene glycol.
• the water-organic solvent ratio may vary.
• the extraction will be carried out, for example, in a 50% ethanol-water mixture or a 20% water-80% ethanol solution.
• the plant / solvent ratio may vary for example and without limitation from 1/4 to 1/20.
• the preparation of the extract begins by grinding the parts of the plant followed by maceration in the extraction solvent for several hours. Extraction can be performed with stirring to improve performance.
• the extraction can be carried out at ambient temperature or by increasing the temperature, for example at 50 ° C. or else at 60 ° C.
• the solution is filtered.
• the solution thus obtained can be concentrated by any method known to those skilled in the art.
• the solution obtained can be lyophilized by any conventional freeze-drying method, thereby obtaining a powder.
• the extract useful for the implementation of the invention may also correspond to pomegranate juice, obtained by pressing the fleshy parts of the fruit.
• This juice may undergo fermentation, concentration and / or lyophilization and / or any operation to facilitate its preservation such as sterilization treatments, known to those skilled in the art.
• the extraction from the pomegranate fruit including the seed can result, according to a particular method of realization, in the preparation of an essential oil.
• the extract in the form of a concentrated solution, as well as the extract in powder form, as well as the extract in the form of an essential oil may be taken up in a suitable medium for oral consumption for humans.
• the extract is chosen from aqueous extracts and alcoholic or hydro-alcoholic extracts of Punica granatum.
• Such extracts are recorded for example with the CAS number 84961-57-9 and for example marketed by the company MMP Inc. under the trade name "Pomegrante Juice extract E40"; other extracts are for example marketed by the company Blue California under the trade name “Pomegrante Extract 70%", or by the company Naturex under the trade name “Pomegranate extract 40%", or by the company Guillin Layn Natural Ingredients under the trade name "Pomegranate Seed PE”.
• the Punica granatum extract is present in a composition suitable for the oral route, containing physiologically acceptable excipients.
• compositions according to the invention are intended to be absorbed by any pathway allowing systemic passage, in particular orally, in order to protect or maintain in good condition the superficial parts of the body, or to improve the appearance of individuals, especially in the skin and its appendages.
• the compositions according to the invention are in particular food supplements.
• the composition according to the invention may contain the extract (s) of Punica granatum in solution in a liquid food such as an aqueous or aqueous-alcoholic solution, optionally flavored. They can also be incorporated in an unmanageable solid carrier and be for example in the form of granules, pills, tablets or dragees. They can also be placed in solution in a food liquid conditioned itself possibly in unmanageable capsules. For ingestion, many embodiments of oral compositions and in particular dietary supplements are possible. Their formulation is carried out by the usual methods for producing dragees, capsules, gels, emulsions, tablets, capsules or solutions.
• the active (s) according to the invention can be incorporated into all other forms of food supplements or fortified foods, for example food bars, or compacted powders or not.
• the powders can be diluted with water, in soda, dairy products or soy derivatives, or incorporated into food bars.
• the active agents according to the invention can be formulated with the excipients and components customary for such oral compositions or food supplements, namely in particular fatty and / or aqueous components, humectants, thickeners, preservatives, texture, flavor and / or coating agents, antioxidants, preservatives and dyes common in the field of food.
• the amount of plant or extract Punica granatum will be adapted by the skilled person depending on the nature of the asset and the desired effect.
• the Punica granatum extract may constitute up to 100% of the composition.
• the extract of Punica granatum will be present in a composition suitable for the oral route at a concentration of between 0.01 and 99% by weight, relative to the total weight of the composition, generally less than or equal to 90% and especially from 0.1 to 50% by weight. Concentrations of 5% to 50% relative to the total weight of the composition, and in particular 40 to 50% may thus be used in accordance with the invention.
• the content of Punica granatum or extract of Punica granatum in the compositions will be adapted so as to result in a daily intake of between 10 mg and 1000 mg of extract of Punica granatum, in particular between 200 mg and 500 mg.
• the compositions or plant extracts of the Punica granatum species according to the invention are useful for reducing and / or preventing and / or delaying the natural whitening of keratin fibers occurring physiologically during aging, more particularly in the body.
• human The human keratinous fibers to which the invention applies are in particular the hair, the eyebrows, the eyelashes, the beard hair, the mustache hair and the pubic hair. More specifically, the invention is applicable to human hair and / or eyelashes.
• the subject of the invention is also a plant plant of the species Punica granatum or one of its extracts for use in preventing and / or treating canities.
• the invention aims to limit, prevent or stop the disappearance of precursors of melanocytes hair.
• the subject of the invention is also a cosmetic treatment method for reducing and / or delaying the whitening of keratinous fibers, in particular the hair and / or the hair and / or promoting their natural repigmentation, characterized in that it is administered orally to a subject at least one plant of the species Punica granatum, or an extract of Punica granatum or a composition containing it.
• the method according to the invention may thus be intended to reduce and / or delay and / or prevent bleaching of the hair and / or hair and / or promote their natural repigmentation.
• the method thus makes it possible to maintain a coloration and a natural pigmentation of human hair, especially in subjects over 35 years of age or over 45 years old.
• Oral intake of Punica granatum extract may be associated with topical application to the skin or integuments of an extract of Punica granatum, identical or different from that ingested.
• At least one additional agent that is beneficial to the hair and / or hair is applied to the subject. bristles or reducing their bleaching, or an agent promoting hair growth or decreasing hair loss, an agent improving the quality of the hair fiber such as a hair loss reducing agent or strengthening the capillary diameter, or an anti-hair loss agent; dandruff or fight against desquamative conditions of the hair.
• This application can be performed by any route, including topical or oral.
• compositions containing the extract of Punica granatum also contain at least one other agent that promotes the pigmentation of the hair or the hair, and / or at least one agent that promotes hair regrowth or decreasing their fall.
• agents that modulate the differentiation and / or proliferation and / or pigmentation of skin cells such as retinol and its esters, vitamin D and its derivatives, cAMP modulators such as the POMC derivatives, adenosine, or forskolin and its derivatives, prostaglandins and their derivatives;
• anti-free radical agents such as ⁇ -tocopherol or its esters, superoxide dismutases or its mimetics, certain metal chelators or ascorbic acid and its esters;
• anti-seborrheic agents such as certain sulfur amino acids, 13-cis retinoic acid, cyproterone acetate;
• desquamating agents of the scalp such as selenium disulphide, climbazole, undecylenic acid, ketoconazole, piroctone olamine (octopirox) or ciclopirocton (ciclopirox)
• plant extracts with pro-pigmenting activity such as chrysanthemum extracts as described in FR 2768343 and extracts of Sanguisorba described in FR 2782920.
• it may be active stimulating the regrowth and / or promoting the slowing down of the hair loss, it may more particularly be mentioned without limitation:
• nicotinic acid esters including in particular tocopherol nicotinate, benzyl nicotinate and C-alkyl nicotinates; -Cg such as methyl or hexyl nicotinates;
• pyrimidine derivatives such as 2,4-diamino-6-piperidinopyrimidine 3-oxide or "Minoxidil” described in US Pat. Nos. 4,139,619 and 4,596,812; Aminexil or 2,4 diamino pyrimidine 3 oxide described in WO96 / 09048;
• lipoxygenase or cyclooxidase inducing agents promoting hair regrowth such as those described by the Applicant in the European patent application EP 0 648 488;
• calcium antagonists such as Cinnarizine, Nimodipine and Nifedipine;
• the additional agent may especially be chosen from the group comprising at least one extract of a plant selected from Fragaria (strawberry), blackberry, raspberry, grape, nut, terminalia (in particular Belerica, Chebula and Arjuna), Caesalpinia spinosa, cypresses , Burnet, Sanguisorba officinalis or chrysanthemum (Chrysanthemum morifolium) or an agent selected from tyrosine, L-DOPA, pro-opiomelanocortin derivatives, adenosine, or forskolin or its derivatives.
• Fragaria strawberry
• blackberry blackberry
• raspberry raspberry
• grape nut
• terminalia in particular Belerica, Chebula and Arjuna
• cypresses Burnet
• Sanguisorba officinalis or chrysanthemum (Chrysanthemum morifolium)
• At least one additional agent is applied topically to the skin and / or its annexes.
• At least one additional agent in particular at least one additional agent beneficial for the hair as defined above, in particular promoting the natural repigmentation of the hair or reducing their whitening, is administered orally.
• composition adapted to the implementation of the invention also contains at least one extract of a plant selected from raspberry, blackberry (raspberry, blackberry), strawberry, grape, nut, terminalia (in particular Belerica, Chebula and Arjuna), Caesalpinia Spinosa.
• Punica granatum The plant Punica granatum, its extracts or the composition containing them will be ingested regularly, daily in particular 1 to 3 times a day.
• the treatment of Punica granatum may be continued over time, for example for 2 to 4 weeks, but may be continued for 2 to 6 months without inconvenience.
• the method according to the invention is a cosmetic process which makes it possible to improve the appearance of the hair, in particular by delaying or reducing the physiological whitening.
• pomegranate extract according to the invention makes it possible to obtain a good tolerance and a good effectiveness of the cosmetic treatment. In addition, improved formulations are obtained.
• the invention also relates to an extract of at least one plant of the species Punica granatum for use in preventing and / or treating canities.
• the invention also relates to a combination product for simultaneous, separate or sequenced use in time, characterized in that it comprises at least
• a second component comprising an additional active agent promoting the natural pigmentation of the hair or reducing its whitening, chosen from extracts of a plant selected from Fragaria (strawberry), blackberry, raspberry, grape, nut, Terminalia (in particular Belerica, Chebula and Arjuna) and Caesalpinia spinosa.
• the human hair follicles are micordisséqués and placed in culture in vitro in the culture medium William's E (Gibco-BRL) supplemented in particular with glutamine, insulin, hydrocortisone and antibiotics.
• the culture medium contains 2-Thiouracil [ 14 C] at a concentration of 3 ⁇ / ⁇ .
• the culture medium is supplemented with pomegranate extract.
• the culture medium is supplemented with the vehicle (in the same quantity as for the "test” group).
• the hair follicles are washed with medium without 2-Thiouracil [ 14 C]; then lysed by immersion in a solution of Soluene 350 heated to 50 ° C. A scintillating liquid is then added. The amount of 2-Thiouracil [ 14 C] present in the lysates is measured using TRILUX 1450 Micro-Beta.
• Pomegranate extract increases the incorporation of 2-thiouracil [ 14 C] into hair follicles.
• the level of expression of these bio markers of canities is analyzed by the standard technique of quantitative RT-PCR (Q-RT-PCR) in human hair follicles.
• Q-RT-PCR quantitative RT-PCR
• the human hair follicles of white hair are microdissected and placed in culture in vitro in the William's E culture medium (Gibco-BRL) supplemented in particular with glutamine, insulin, hydrocortisone and antibiotics.
• the culture medium is supplemented with Punica granatum extract.
• the control group (30 follicles)
• the culture medium is supplemented with the vehicle (in the same quantity as for the "test” group).
• the time necessary for the revelation of the activity of the extract generally from 24h to 5 days, the mRNAs of the hair follicles are extracted. MRNAs of the same experimental condition are grouped together.
• the expression level of the interest mRNAs is determined by a conventional method
• Q-RT-PCR for example using QuantiTect kit SYBR Green RT-PCR reference 204243 from Qiagen, the measurement that can be performed on the MylQ device of BIORAD.
• the extract of Punica granatum corrects the expression changes of some bio markers of canities in the hair follicles of white hair.
• Example 2 Formula type Gellule Active gelatin mg / sugar

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• 2009
  • 2009-10-30 FR FR0957663A patent/FR2951938B1/fr not_active Expired - Fee Related
• 2010
  • 2010-10-29 WO PCT/FR2010/052327 patent/WO2011051633A2/fr active Application Filing
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