WO2007107856A1 - Magnolia champaca oil, its process of preparation and compositions comprising it - Google Patents
Magnolia champaca oil, its process of preparation and compositions comprising it Download PDFInfo
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- WO2007107856A1 WO2007107856A1 PCT/IB2007/000697 IB2007000697W WO2007107856A1 WO 2007107856 A1 WO2007107856 A1 WO 2007107856A1 IB 2007000697 W IB2007000697 W IB 2007000697W WO 2007107856 A1 WO2007107856 A1 WO 2007107856A1
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B9/00—Essential oils; Perfumes
- C11B9/02—Recovery or refining of essential oils from raw materials
- C11B9/027—Recovery of volatiles by distillation or stripping
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
-
- 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
- A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
- A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- 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
- A61P17/18—Antioxidants, e.g. antiradicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- 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
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B1/00—Production of fats or fatty oils from raw materials
- C11B1/10—Production of fats or fatty oils from raw materials by extracting
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B3/00—Refining fats or fatty oils
- C11B3/12—Refining fats or fatty oils by distillation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/522—Antioxidants; Radical scavengers
Definitions
- Magnolia champaca oil its process of preparation and compositions comprising it
- the invention relates to an oil extracted from the flowers of at least one type of Magnolia champaca, to its process of preparation, to a cosmetic, pharmaceutical or dermatological composition comprising it and to its use as polyfunctional active agent in a pharmaceutical, cosmetic or dermatological composition for the prevention and/or treatment of detrimental changes in the skin due in particular to aging or to physiological mechanisms related to aging or to disorders connected with these mechanisms.
- the skin is composed mainly of three layers, namely, starting from the outermost, the epidermis, the dermis and the hypodermis .
- the external layer of the skin is stratified and contributes greatly to providing protection of the skin with regard to external attacks.
- the dermis is a connective tissue which provides both the functions of cohesion and of nutrition of the skin.
- Intrinsic or chronobiological aging corresponds to "normal” or physiological aging related to age.
- Extrinsic aging corresponds to the aging brought about generally by the environment and more particularly to photoaging due to exposure to the sun.
- the present invention is concerned with intrinsic or physiological skin aging and with extrinsic skin aging.
- Skin aging results from a transformation of the connective tissues and from the decline in the capability for cell regeneration. This effect is expressed by the appearance of fine lines and marks over time.
- the microcirculation decreases in the superficial dermis.
- the macromolecules, such as collagen, elastin and glycosaminoglycans , of which hyaluronic acid is one of the constituents, are chemically modified.
- the actual thickness of the dermis regresses, the fibers deteriorate and the skin loses its biomechanical and elastic properties.
- the phenomena of chemical and enzymatic oxidation become more marked with age and result in an increase in the bridging reactions between the fibers, such as collagen fibers.
- the plant Magnolia champaca also known in the literature as Michelia champaca, is a shrub belonging to the family of the Magnoliaceae, originating from the wet and wooded regions of China.
- the essential oil from its flowers is commonly used in perfumery.
- Application JP 07/061918 discloses a cosmetic composition comprising an extract of Michelia champaca obtained by extraction using a polar solvent and its use as antioxidant.
- compositions comprising an extract of Michelia champaca L., having a whitening activity on the skin or an activity of scavenging active oxygen or an antibacterial activity, are disclosed in application JP-A-2000/095663.
- Application JP-A-2005/068075 relates to UV-inhibiting compositions which absorb UVA and UVB rays and which comprise an aqueous extract of a Michelia champaca plant.
- an oil extracted from flowers of at least one type of Magnolia champaca exhibited, via stimulation or inhibition of physiological mechanisms, activities capable of having an effect on the symptoms due to aging or to physiological mechanisms related to aging or to disorders connected with these mechanisms in the epidermis and/or dermis.
- oil is understood to mean a product which is obtained by extraction using a nonpolar solvent and which is very rich in water-insoluble compounds.
- the invention thus relates, according to a first aspect, to an oil extracted from flowers of at least one type of Magnolia champaca, characterized in that it comprises:
- proportions being expressed as relative percentages with respect to the combined constituents separated by gas chromatography.
- the oil according to the invention originates from Magnolia champaca, variety gold, also known as “flower of gold”.
- the term "content expressed as relative percentages with respect to the combined constituents separated by gas chromatography” is understood to mean that the content of each of the constituents is determined with respect to the combined constituents separated by the chromatographic system. Only the compounds extracted by the solvent during the sample preparation and which can vaporize in the injector are present.
- the sample has to be prepared according to standard NF T 60-233 of May 1977, "Preparation des esters methyliques d'acides gras", ( ⁇ 5.2 - Methode applicable aux corps gras acides et acides gras) ["Preparation of the methyl esters of fatty acids” ( ⁇ 5.2 - Method applicable to acidic fatty substances and fatty acids)].
- the chromatographic conditions are described in standard NF EN ISO 5508 of June 1995.
- the method consists in esterifying the fatty acids in an acidic methanolic medium, in then extracting them with heptane and in then injecting the heptane solution in gas chromatography.
- the oil according to the invention comprises:
- proportions being expressed as relative percentages with respect to the combined constituents separated by gas chromatography .
- the invention also relates, according to a subsequent aspect, to a process for the preparation of a Magnolia champaca oil as defined above comprising at least one molecular distillation stage.
- the starting material employed consists, for example, of freshly picked flowers (fresh flowers) of at least one type of Magnolia champaca, preferably Magnolia champaca variety gold, which can be conventionally milled or reduced to pieces .
- the flowers are subject to extraction by at least one nonpolar solvent, for example hexane, cyclohexane, heptane, isooctane, supercritical CO 2 or dichloromethane .
- the extraction is generally carried out by immersing or gently agitating the flowers in one or more of the abovementioned solvents at temperatures ranging, for example, from ambient temperature to 100 0 C for a period of time from approximately 30 min to 12 h.
- the extraction can be repeated several times .
- the solutions are combined and filtered in order to remove the insoluble parts of the flowers.
- the solvent if it is a volatile solvent, such as, for example, hexane or heptane or cyclohexane, is also removed.
- This extraction stage is conventional in the field of plant extracts and a person skilled in the art is in a position to adjust the reaction parameters thereof on the basis of his general knowledge.
- a fractionation stage can be carried out in order to purify the product obtained on conclusion of the extraction.
- Use will preferably be made of a solvent or a mixture of solvents chosen from Ci-C 4 alcohols, such as, for example, methanol, ethanol, isopropanol, and the like, polyols, such as, for example, propylene glycol, dipropylene glycol, and the like, or organic solvents, such as ethyl acetate, hexane, cyclohexane or any other solvent usual in the field.
- Ci-C 4 alcohols such as, for example, methanol, ethanol, isopropanol, and the like
- polyols such as, for example, propylene glycol, dipropylene glycol, and the like
- organic solvents such as ethyl acetate, hexane, cyclohexane or any other solvent usual in the field.
- Fractionation by a supercritical fluid preferably by supercritical CO2, can also be used.
- said concrete is subjected to a molecular distillation stage carried out in a wiped-film and short- path distillation device.
- the invention thus relates to a process for the preparation of a Magnolia champaca oil as defined above comprising the stages consisting in:
- Wiped-film and short-path molecular stills are preferred in carrying out the molecular distillation stage. They comprise a distillation chamber provided with a rotating wiping device which makes it possible to continuously spread, over the evaporation surface (hot surface) product to be distilled. The product vapors are condensed using a cooled finger placed at the center of the distillation chamber. Recovery of the residues and distillate takes place by gravitational flow. The object of this technique is to separate the constituents of the complex mixtures by profiting from their different boiling points.
- Wiped-film and short-path molecular distillation has the advantage of reducing the distillation temperature, as the distillation is carried out under a high vacuum, and of also reducing the residence time of the mixture to be separated in the still. The rate of decomposition of the products increases enormously as a function of the temperature and of the exposure time and, in a still of "alembic" type, for example, the mixtures may remain at high temperatures for hours, which results in denaturation.
- the mixture of the concrete obtained after extraction and optionally fractionation and of the heavy solvent is introduced at a constant flow rate, at a temperature of between 20 and 120 0 C, preferably between 50 and 100 0 C, onto the hot wall of a cylindrical evaporator.
- the volatile product On contact with the latter, and under the very low pressure prevailing in the evaporator, of the order of 10 mbar to 0.001 mbar, the volatile product is then partially and gradually evaporated while the less volatile product flows along the wall.
- the vapors given off are condensed on the cold wall concentric with the hot wall and placed a very short distance from the latter, preferably at a temperature of between 40 and 120 0 C, in particular between 60 and 100 0 C.
- the products separated during operation flow by gravity along the hot and cold walls.
- the distillate is recovered and is subjected, if appropriate, to an additional separation operation (filtration or centrifuging, for example) .
- a Magnolia champaca oil according to the invention is thus obtained.
- said oil is light in color. Furthermore, said oil is devoid of solvent or of any other chemical reactant which was involved during its extraction.
- said oil is provided in a sufficiently concentrated form to be able to be used without causing the formulation problems normally related to the concentrations necessary in order to obtain an activity in the cosmetic, pharmaceutical or dermatological compositions in the emulsion form and without exhibiting a dark color, contrary to the plant extracts obtained by standard processes, when they are in the concentrated form.
- the oil according to the invention can be used directly for the preparation of a cosmetic, pharmaceutical or dermatological composition.
- the invention also relates to the Magnolia champaca oil capable of being obtained by the process described above.
- the invention relates to the use of a Magnolia champaca oil as described above as polyfunctional active agent in a cosmetic, pharmaceutical or dermatological composition for the prevention and/or treatment of detrimental changes in the skin due to aging or to physiological mechanisms related to aging or to disorders connected with these mechanisms.
- the invention relates to the use of a Magnolia champaca oil as described above in a cosmetic composition as agent which improves healing or cell repair and/or agent for activating the metabolism of the cells of the epidermis and/or agent for scavenging free radicals and/or agent for detoxifying the epidermis.
- the invention also relates to the use of a Magnolia champaca oil as described above as agent which improves healing or cell repair and/or agent for activating the metabolism of the cells of the epidermis and/or agent for scavenging free radicals and/or agent for protecting nuclear DNA and/or agent for protecting mitochondrial DNA and/or agent for detoxifying the epidermis, for the preparation of a pharmaceutical or dermatological composition.
- the invention thus relates more particularly to the use of a Magnolia champaca oil as described above as agent which inhibits the synthesis of melanin, in particular as agent which inhibits the synthesis of endothelin, in a cosmetic, pharmaceutical or dermatological composition.
- Endothelin is a messenger protein which promotes the proliferation of the melanocytes and the increase in melanogenesis responsible for the pigmentation of the skin related to aging ("liver spots") .
- the invention relates in particular to the use of a Magnolia champaca oil as described above as agent which inhibits the transcription factor MITF (Microphthalmia- associated Transcription Factor) , a factor for regulating and differentiating melanocytes, in a cosmetic or dermatological composition.
- MITF Microphthalmia- associated Transcription Factor
- Magnolia champaca oil according to the invention stimulates the synthesis of several families of growth factors by keratinocytes .
- PDGF platelet-derived growth factor
- mitogenic activity on the majority of the cells derived from the mesenchyme (Lepisto J. et al . , 1995, Biochem. Biophys . Res. Commun., 209(2), 393-9) and stimulates the synthesis of collagen and collagenase by these cells, thus playing a role in physiological processes, such as healing and tissue repair (Tan E. M. et al., Biochem.
- VEGF vascular endothelial growth factor
- the epidermis is an important source of VEGF, secreted in large amounts by proliferating keratinocytes .
- the mRNA of VEGF is expressed by normal keratinocytes, both in the tissue in situ and in cell culture. It has been shown that VEGF would maintain the homeostasis of endothelial cells and their ability to respond to an angiogenic stimulation, even in elderly subjects (Watanabe Y. et al . , 1997, Oncogene, 14, 2025- 2032) .
- VEGF vascular endothelial growth factor
- HB-EGF or heparin-binding epidermal growth factor which plays an important role in the regulation and differentiation of keratinocytes (Iwamoto et al., Cytokine and Growth Factors Reviews, 2000, 11, 335-344) and in the senescence of young cells, the growth of which depends on this factor (JID Suppl., 24, S46-S50; Kanzaki Y. et al., Exp. Cell. Res., 2002, 279(2), 321- 329) .
- activator of the synthesis of several families of growth factors is understood to mean, according to the invention, any molecule capable of stimulating the activity and/or the expression and/or the release of at least one of these growth factors expressed and/or synthesized by and in keratinocytes .
- the invention thus relates to the use of a Magnolia champaca oil as described above as agent which activates the synthesis of at least one cell growth factor by keratinocytes, in particular as agent which activates at least one growth factor chosen from PDGF, VEGF and HB-EGF, in a cosmetic, pharmaceutical or dermatological composition.
- the invention also relates to the use of a Magnolia champaca oil as described above as agent which inhibits the activity of the enzymes involved in the degradation of the matrix, in particular matrix metalloproteinases (MMPs) and very particularly MMP3 (or stromelysin 1) and MMP9 (or gelatinase B) .
- MMPs matrix metalloproteinases
- MMP3 or stromelysin 1
- MMP9 or gelatinase B
- Matrix metalloproteinases are enzymes (endoproteases) which degrade the extracellular matrix in the context of the physiological remodeling of the skin. Age and exposure to endoproteases
- UV irradiation of A and/or B type have the consequence of increasing activity of these MMPs, in particular that of
- MMP3 or stromelysin 1
- MMP9 or gelatinase B
- metaloproteinase inhibitor is understood to mean, according to the invention, any molecule capable of inhibiting the activity and/or the expression and/or the release of at least one of the metalloproteinases expressed and/or synthesized by and in the skin.
- the invention also relates, according to preferred aspects, to the use, as antioxidant, of a Magnolia champaca oil as described above in a cosmetic composition or for the preparation of a pharmaceutical or dermatological composition.
- the invention also relates, according to preferred aspects, to the use, as agent which stimulates the cell metabolism, of a Magnolia champaca oil as described above in a cosmetic composition or for the preparation of a pharmaceutical or dermatological composition.
- the invention also relates, according to preferred aspects, to the use, as agent for detoxifying the epidermis as a result of oxidative stress, in particular by stimulating the synthesis of DT diaphorase (NQOl) , which catalyzes the detoxification of quinones, and also by stimulating the synthesis of glutathione S-transferase, which catalyzes the detoxification of chemical metabolites, such as lipid peroxidation products, of a Magnolia champaca oil as described above in a cosmetic composition or for the preparation of a pharmaceutical or dermatological composition.
- NQOl DT diaphorase
- glutathione S-transferase which catalyzes the detoxification of chemical metabolites, such as lipid peroxidation products, of a Magnolia champaca oil as described above in a cosmetic composition or for the preparation of a pharmaceutical or dermatological composition.
- the invention also relates, according to another preferred aspect, to the use, as agent which stimulates cellular energy, in particular cytochrome C and AMP kinase, of a Magnolia champaca oil as described above in a cosmetic composition or for the preparation of a pharmaceutical or dermatological composition.
- Cytochrome C oxidase the final stage in the electron transport chain, is crucial for cellular respiration and also contributes to the synthesis of cellular ATP (Lalla A. et al., West Indian Med. J., 2001, June, 50(2), 111-6).
- the energy status of the cell is coordinated by the AMP- activated protein kinase (AMPK) system and also contributes to the ATP content of the cell (Dagon Y. et al., J. Biol. Chem., 2005, 23, 280(51), 42142-8).
- AMPK AMP- activated protein kinase
- the invention also relates, according to a subsequent aspect, to a cosmetic composition or a pharmaceutical or dermatological composition comprising a Magnolia champaca oil as described above and a cosmetically or pharmaceutically acceptable vehicle.
- said extract is present in the cosmetic, pharmaceutical or dermatological composition in a proportion of 0.001 to 10% by total weight of the composition, in particular in a proportion of 0.01 to 5%, preferably of 0.1 to 1%, by total weight of the composition.
- Said cosmetic, pharmaceutical or dermatological composition can in particular be appropriate for application by the topical route.
- said cosmetic, pharmaceutical or dermatological composition can be provided in the form of a powder, of an emulsion, of a microemulsion, of a nanoemulsion, of a suspension, of a solution, of a lotion, of a cream, of an aqueous or aqueous/alcoholic gel, of a foam, of a serum, of an aerosol solution or dispersion or of a dispersion of lipid vesicles.
- an emulsion in the case of an emulsion, it can be a water-in-oil or oil-in-water emulsion.
- the cosmetic, pharmaceutical or dermatological composition according to the invention also comprises a solvent chosen according to the various ingredients and the administration form. Mention may be made, by way of examples, of water (preferably demineralized water) , an alcohol, such as ethanol, or a diethylene glycol ether, such as ethoxydiglycol or diethylene glycol monomethyl ether.
- a solvent chosen according to the various ingredients and the administration form. Mention may be made, by way of examples, of water (preferably demineralized water) , an alcohol, such as ethanol, or a diethylene glycol ether, such as ethoxydiglycol or diethylene glycol monomethyl ether.
- Said cosmetic, pharmaceutical or dermatological composition can also comprise at least one additive conventional in the field, such as, for example, at least one compound chosen from an emollient or humectant, a gelling and/or thickening agent, a surface-active agent, an oil, an active agent, a dye, a preservative, an antioxidant, a chelating agent, an organic or inorganic powder, a pigment, a self-tanning agent, a sunscreen, an essential oil and a fragrance.
- at least one additive conventional in the field such as, for example, at least one compound chosen from an emollient or humectant, a gelling and/or thickening agent, a surface-active agent, an oil, an active agent, a dye, a preservative, an antioxidant, a chelating agent, an organic or inorganic powder, a pigment, a self-tanning agent, a sunscreen, an essential oil and a fragrance.
- said composition can comprise :
- humectant chosen, for example, from polyols, such as glycerol, propylene glycol, butylene glycol, polyethylene glycol, sugars or their derivatives, urea, glycolic acid or its salts, lactic acid or its salts, or hyaluronic acid.
- polyols such as glycerol, propylene glycol, butylene glycol, polyethylene glycol, sugars or their derivatives, urea, glycolic acid or its salts, lactic acid or its salts, or hyaluronic acid.
- Said humectant will be present in the composition at a content of the order of 0.01 to 20%, preferably 0.5 to 10%, by total weight of the composition.
- One or more emollient chosen, for example, from volatile or nonvolatile silicones (dimethicone, cyclomethicone, dimethiconol, and the like) , long-chain hydrocarbons, or esters of fatty acids or of fatty alcohols .
- Said emollient will be present in the composition at a content of the order of 0.5 to 30%, preferably 0.5 to 15%, by total weight of the composition.
- Non-film-forming gelling agents can, for example, be chosen from clays (laponite) , ammonium acryloyldimethyltaurate/VP copolymer and ammonium acryloyldimethyltaurate/beheneth-25 methacrylate copolymer (such as, for example, those sold under the names Aristoflex AVC and HMB by Clariant) .
- Said gelling and/or thickening agent will be present in the composition at a content of the order of 0 to 10% by total weight of the composition, preferably 0.1 to 5% by total weight of the composition.
- One or more surface-active agent (s) or cosurfactant (s) preferably nonionic, present in a content of the order of 0.01 to 10%, preferably 0.1 to 5%, by total weight of the composition.
- oil(s) which is (are) liquid or solid at ambient temperature
- oil(s) which may be volatile or nonvolatile, which may be hydrocarbon- or silicone-based and which may be linear, cyclic or branched, or butter (s), for example isododecane, cyclopentadimethylsiloxane, dimethicone, isononyl isononanoate, pentaerythrityl tetraisostearate, triglycerides of caprylic and capric acid, shea butter, and the like, preferably in a proportion of 0.01 to approximately 15%, preferably 0.1 to 10%, by total weight of the composition.
- One or more active agent (s) of natural, biotechnological or synthetic origin having a biological activity and having an effectiveness on the skin via biological sites, for example chosen from vitamins, trace elements, allantoin, plant proteins, plant extracts, and the like.
- said active agent can be an algal extract .
- One or more water-soluble dye(s) such as, for example, the disodium salt of ponceau, the disodium salt of alizarin green, quinoline yellow, the trisodium salt of amaranth, the disodium salt of tartrazine, the monosodium salt of rhodamine, the disodium salt of fuchsin, or xanthophyll, preferably in a proportion of 0 to approximately 2% by total weight of the composition.
- composition according to the invention can also be present in the composition according to the invention, in particular preservatives, chelating agents, antioxidants, essential oils or fragrances well known in the technical field.
- Example 1 Process for the preparation of a Magnolia champaca oil according to the invention
- the reactor is emptied of the hexane solution.
- the charged solvent is retained.
- Example 2 Analysis of the composition of a Magnolia champaca oil according to the invention
- the sample thus esterified is recovered by liquid/liquid extraction with 2 ml of heptane and injected in gas chromatography. Chromatography is carried out under the following conditions :
- Carrier gas helium at 1 ml/min.
- Detection flame ionization detector (auxiliary gas nitrogen) .
- the constituents were identified by mass spectrometry.
- Example 3 Study of the activity of Magnolia champaca oil according to the invention with regard to the growth factor HB-EGF
- Keratinocytes derived from neonatal foreskins (Clonetics,
- KBM keratinocyte growth
- a modified culture medium supplemented with recombinant human EGF, insulin, hydrocortisone, bovine pituitary extract, gentamycin and amphotericin B.
- the cells After culturing for 24 h in an incubator at 37°C, 5% CO 2 and with saturated humidity, the cells are washed with PBS buffer pH 7.4 (Gibco) and incubated with specific basic medium (KBM, Clonetics) comprising the products to be tested, for 6 h or 24 h according to the tests, at different concentrations.
- PBS buffer pH 7.4 Gibco
- KBM specific basic medium
- a control without product to be tested (“untreated") is also carried out by keeping the cells in the same medium without treatment .
- a positive control is optionally carried out with a reference product for the activity tested.
- RT-PCR real-time polymerase chain reaction
- the results are expressed as number of times the target gene (HB-EGF) expression is increased or decreased in the treated sample, and not as absolute number of copies.
- the sequences of the cDNAs/mRNAs of the genes investigated were obtained from GenBank.
- Target gene HB-EGF Housekeeping gene: PBDG
- the mRNA was isolated using the Trizol reagent (Invitrogen) according to the manufacturer's recommendations.
- the reverse transcription was carried out using the GeneAmp RNA PCR kit (Applied Biosystems) according to the manufacturer's recommendations.
- the real-time PCR measurement was carried out using the LightCycler technology (Roche Applied Science) with SYBR
- the cDNA was amplified using a standardized program. Each LightCycler capillary was charged with 1.5 ⁇ l of DNA Master mix, 1.8 ⁇ l of MgCl 2 (25 mM) , 10.1 ⁇ l of water and 0.5 ⁇ l of each primer (10 ⁇ M stock) . The final amount of cDNA per reaction corresponded to 25 ng of total RNA used for the reverse transcription .
- the specificity of the PCR was tested by agarose gel electrophoresis and sequencing, and was evaluated for each sample using a melting point analysis included in the PCR program.
- TNF ⁇ tumor necrosis factor ⁇
- the results show that the Magnolia champaca oil according to the invention has a stimulatory activity with respect to the synthesis of HB-EGF mRNA.
- Example 4 Study of the activity of Magnolia champaca oil according to the invention with regard to the growth factor VEGF
- the measurement was carried out by RT-PCR in the same way as in example 3.
- the sequences of the cDNAs/mRNAs of the genes investigated were obtained from GenBank.
- Target gene VEGF
- the keratinocyte culture conditions are as described in example 3.
- the results show that the Magnolia champaca oil according to the invention has a stimulatory activity with respect to the synthesis of VEGF mRNA.
- Example 5 Study of the activity of Magnolia champaca oil according to the invention with regard to the growth factor PDGF-AA
- the quantitative evaluation of the concentrations of human PDGF-AA growth factor in the cell cultures was carried out using the ELISA method by employing the Quantikine ® immunological assay kit (No. DAA00, R&D Systems) .
- the keratinocyte culture conditions and the samples tested are as described in example 3.
- the results show that the Magnolia champaca oil according to the invention has a stimulatory activity with respect to the synthesis of PDGF-AA.
- Example 6 Study of the activity of Magnolia champaca oil according to the invention with regard to endothelin-1 The quantitative evaluation of the concentrations of human endothelin-1 in the cell cultures was carried out using the ELISA method by employing the Quantikine ® immunological assay kit (No. BBE5, R&D Systems) .
- the keratinocyte culture conditions and the samples tested are as described in example 3.
- Example 7 Study of the activity of Magnolia champaca oil according to the invention with regard to MITF
- Target gene MITF
- Example 8 Study of the activity of Magnolia champaca oil according to the invention with regard to matrix ⁇ ietalloproteinases (MMPs)
- the products to be tested are incubated with the activated MMPs.
- the enzymatic activity is controlled by the addition of a fluorescent enzymatic substrate specific for each MMP.
- Pro-MMP3 or pro-MMP9 are incubated in plates with a 1 mM APMA (p-aminophenylmercuric acetate) solution at ambient temperature, with gentle stirring, for 1 h.
- APMA p-aminophenylmercuric acetate
- the enzymatic reaction is monitored for 1 h using a spectrofluorimeter and the fluorescence is measured at an excitation wavelength of 360 nm and an emission wavelength of 460 nm for MMP3 (or stromelysin 1) and at an excitation wavelength of 320 nm and an emission wavelength of 405 nm for MMP9 (or gelatinase B) .
- the results are expressed in units of fluorescence emitted (RFU) , which represents the amount of substrate hydrolyzed per min.
- the Microwin 2000 spectrofluorimeter calculates the variation in absorbance ⁇ , which represents the initial rate (Vi) of the enzymatic reaction.
- ⁇ represents the initial rate (Vi) of the enzymatic reaction.
- Vi the initial rate of the enzymatic reaction.
- the mean of the 3 values of Vi obtained for each concentration of potential inhibitor is calculated.
- the results of 10 experiments were expressed as mean ⁇ SD and then presented as percentage of residual activity.
- EDTA ethylenediamine- tetraacetic acid
- Example 9 Study of the activity of Magnolia champaca oil according to the invention with regard to the synthesis of DT diaphorase
- the cells After having prepared the cells according to the protocol of example 3, the cells are lyzed for their analysis by Western blotting. After the quantification of the proteins according to the kit (Pierce Chemical Co., NY), the proteins are fractionated on a gel gradient. The polyvinylidene difluoride (PVDF) membranes resulting from the transfer from the gels are incubated in the presence of an anti-NQOl polyclonal antibody (Genetex, San Antonia, TX) . After rinsing, the membranes are developed by a "Supersignal West Dura" detection kit (Pierce Chemical Co., NY) and the bands are quantified by image analysis.
- PVDF polyvinylidene difluoride
- Example 10 Study of the activity of Magnolia champaca oil according to the invention with regard to the synthesis of glutathione S-transferase (GST) After having prepared the cells according to the protocol of example 3, the cells are lyzed and the supernatants recovered. The activity of GST is evaluated by the use of the "GST Activity Assay Kit” (Biodivision, Mountain View, CA) according to the protocol described by the supplier of the kit .
- the results show that the Magnolia charnpaca oil according to the invention stimulates the synthesis of glutathione S- transferase .
- Example 11 Study of the activity of Magnolia champaca oil according to the invention with regard to the synthesis of cellular cytochrome C
- the amount of cytochrome C in the lysates of the keratinocytes prepared according to the protocol of example 3 is quantified with the "Cytochrome C ELISA Kit” (Zymed ® ) .
- Example 12 Study of the activity of Magnolia champaca oil according to the invention with regard to the synthesis of AMP kinase
- the cells After having prepared the cells according to the protocol of example 3, the cells are lyzed for their analysis by
- Example 13 Study of the antioxidant activity of Magnolia champaca oil according to the invention
- Magnolia champaca oil according to the invention has an antioxidant activity with regard to the hydroxyl radical.
- BSA bovine serum albumin
- vitamin C ascorbic acid
- Ascorbic acid is well known for its role in the formation of superoxide radicals. Table 15
- Magnolia champaca oil according to the invention has an antioxidant activity with regard to the superoxide radical.
- Example 14 Eye contour cream comprising a Magnolia champaca oil according to the invention
- Example 15 Face cream comprising a Magnolia champaca oil according to the invention
Abstract
The invention relates to an oil extracted from flowers of at least one type of Magnolia champaca, to its process of preparation, to the cosmetic, pharmaceutical or dermatological compositions comprising it and to its use as polyf unctional active agent for the prevention and/or treatment of detrimental changes to the skin.
Description
Magnolia champaca oil, its process of preparation and compositions comprising it
The invention relates to an oil extracted from the flowers of at least one type of Magnolia champaca, to its process of preparation, to a cosmetic, pharmaceutical or dermatological composition comprising it and to its use as polyfunctional active agent in a pharmaceutical, cosmetic or dermatological composition for the prevention and/or treatment of detrimental changes in the skin due in particular to aging or to physiological mechanisms related to aging or to disorders connected with these mechanisms.
The skin is composed mainly of three layers, namely, starting from the outermost, the epidermis, the dermis and the hypodermis .
The external layer of the skin, the epidermis, is stratified and contributes greatly to providing protection of the skin with regard to external attacks. The dermis is a connective tissue which provides both the functions of cohesion and of nutrition of the skin.
Skin aging results from two separate and independent processes which involve intrinsic or extrinsic factors.
Intrinsic or chronobiological aging corresponds to "normal" or physiological aging related to age.
Extrinsic aging corresponds to the aging brought about generally by the environment and more particularly to photoaging due to exposure to the sun.
The present invention is concerned with intrinsic or physiological skin aging and with extrinsic skin aging.
Skin aging results from a transformation of the connective tissues and from the decline in the capability for cell regeneration. This effect is expressed by the appearance of fine lines and marks over time. The microcirculation decreases in the superficial dermis. The macromolecules, such as collagen, elastin and glycosaminoglycans , of which hyaluronic acid is one of the constituents, are chemically modified. The actual thickness of the dermis regresses, the fibers deteriorate and the skin loses its biomechanical and elastic properties. The phenomena of chemical and enzymatic oxidation become more marked with age and result in an increase in the bridging reactions between the fibers, such as collagen fibers.
The detrimental changes associated with aging can be expressed in different ways, among which may be mentioned:
a disorganization of the elastin fibers, resulting in a loss of firmness, of flexibility and of elasticity or the appearance of telangiectasia; the loss in radiance due to the reduction in the microcirculation and to a slowing down in cell replacement in the epidermis and the appearance of fine wrinkles or fine lines,- - the yellowing of the skin, which develops a parchment- like look accompanied by the appearance of pigmentary blemishes which are associated with a dysfunctioning in the synthesis of melanin (or melanogenesis) ; skin dryness resulting from a reduction in the barrier function of the horny layer and from a slowing down in epidermal replacement .
For this reason, there exists a need to provide a polyfunctional active agent capable of having an effect on a combination of causes of detrimental changes in the skin due to aging and/or to a modification in the physiological mechanisms related to aging or the like.
The plant Magnolia champaca, also known in the literature as Michelia champaca, is a shrub belonging to the family of the Magnoliaceae, originating from the wet and wooded regions of China. The essential oil from its flowers is commonly used in perfumery.
Application JP 07/061918 discloses a cosmetic composition comprising an extract of Michelia champaca obtained by extraction using a polar solvent and its use as antioxidant.
Compositions comprising an extract of Michelia champaca L., having a whitening activity on the skin or an activity of scavenging active oxygen or an antibacterial activity, are disclosed in application JP-A-2000/095663.
Application JP-A-2005/068075 relates to UV-inhibiting compositions which absorb UVA and UVB rays and which comprise an aqueous extract of a Michelia champaca plant.
The antiinflammatory and antipyretic activity of methanolic extracts of Michelia champaca L. (white variety) is described by R. Vimala et al . , Indian J. Exp. Biol., 1997, 35, 1310-1314.
The authors of the present invention have now demonstrated, entirely surprisingly, that an oil extracted from flowers of at least one type of Magnolia champaca exhibited, via stimulation or inhibition of physiological mechanisms, activities capable of having an effect on the symptoms due to aging or to physiological mechanisms related to aging or to disorders connected with these mechanisms in the epidermis and/or dermis.
This observation has led to the development of novel cosmetic, pharmaceutical or dermatological compositions of use more particularly for all the applications in which it
is desired to have an effect on the symptoms due to aging or on the physiological mechanisms related to aging or on the disorders connected with these mechanisms in the epidermis and/or dermis.
The term "oil" is understood to mean a product which is obtained by extraction using a nonpolar solvent and which is very rich in water-insoluble compounds.
The invention thus relates, according to a first aspect, to an oil extracted from flowers of at least one type of Magnolia champaca, characterized in that it comprises:
20 to 70% of benzoic ester, - 15 to 35% of saturated and/or unsaturated fatty acids,
said proportions being expressed as relative percentages with respect to the combined constituents separated by gas chromatography.
Preferably, the oil according to the invention originates from Magnolia champaca, variety gold, also known as "flower of gold".
The term "content expressed as relative percentages with respect to the combined constituents separated by gas chromatography" is understood to mean that the content of each of the constituents is determined with respect to the combined constituents separated by the chromatographic system. Only the compounds extracted by the solvent during the sample preparation and which can vaporize in the injector are present.
The sample has to be prepared according to standard NF T 60-233 of May 1977, "Preparation des esters methyliques d'acides gras", (§ 5.2 - Methode applicable aux corps gras
acides et acides gras) ["Preparation of the methyl esters of fatty acids" (§ 5.2 - Method applicable to acidic fatty substances and fatty acids)]. The chromatographic conditions are described in standard NF EN ISO 5508 of June 1995.
Briefly, the method consists in esterifying the fatty acids in an acidic methanolic medium, in then extracting them with heptane and in then injecting the heptane solution in gas chromatography.
Preferably, the oil according to the invention comprises:
from 10 to 40% of cinnamyl benzoate, - from 5 to 30% of phenylethyl benzoate, from 5 to 30% of benzyl benzoate, from 5 to 30% of linoleic acid, from 2 to 20% of linolenic acid,
said proportions being expressed as relative percentages with respect to the combined constituents separated by gas chromatography .
The invention also relates, according to a subsequent aspect, to a process for the preparation of a Magnolia champaca oil as defined above comprising at least one molecular distillation stage.
The starting material employed consists, for example, of freshly picked flowers (fresh flowers) of at least one type of Magnolia champaca, preferably Magnolia champaca variety gold, which can be conventionally milled or reduced to pieces .
The flowers are subject to extraction by at least one nonpolar solvent, for example hexane, cyclohexane, heptane, isooctane, supercritical CO2 or dichloromethane .
The extraction is generally carried out by immersing or gently agitating the flowers in one or more of the abovementioned solvents at temperatures ranging, for example, from ambient temperature to 1000C for a period of time from approximately 30 min to 12 h.
After filtration, the extraction can be repeated several times . The solutions are combined and filtered in order to remove the insoluble parts of the flowers. If appropriate, the solvent, if it is a volatile solvent, such as, for example, hexane or heptane or cyclohexane, is also removed.
This extraction stage is conventional in the field of plant extracts and a person skilled in the art is in a position to adjust the reaction parameters thereof on the basis of his general knowledge.
According to an advantageous aspect of the invention, a fractionation stage can be carried out in order to purify the product obtained on conclusion of the extraction.
Use will preferably be made of a solvent or a mixture of solvents chosen from Ci-C4 alcohols, such as, for example, methanol, ethanol, isopropanol, and the like, polyols, such as, for example, propylene glycol, dipropylene glycol, and the like, or organic solvents, such as ethyl acetate, hexane, cyclohexane or any other solvent usual in the field.
Fractionation by a supercritical fluid, preferably by supercritical CO2, can also be used.
As above, if one or more volatile solvents is (are) used, there will be grounds for removing it or them before passing to the following stage.
On conclusion of the extraction, and optionally of the fractionation stage mentioned above, a Magnolia champaca concrete is obtained. This type of extract is normally used as intermediate in the manufacture of absolutes intended for the perfumery industry.
Advantageously, said concrete is subjected to a molecular distillation stage carried out in a wiped-film and short- path distillation device.
According to a preferred aspect, the invention thus relates to a process for the preparation of a Magnolia champaca oil as defined above comprising the stages consisting in:
- extracting from flowers (preferably fresh flowers) of at least one type of Magnolia champaca using at least one nonpolar solvent, subjecting said extract to at least one molecular distillation stage, and - recovering the distillate.
Wiped-film and short-path molecular stills are preferred in carrying out the molecular distillation stage. They comprise a distillation chamber provided with a rotating wiping device which makes it possible to continuously spread, over the evaporation surface (hot surface) product to be distilled. The product vapors are condensed using a cooled finger placed at the center of the distillation chamber. Recovery of the residues and distillate takes place by gravitational flow. The object of this technique is to separate the constituents of the complex mixtures by profiting from their different boiling points. Wiped-film and short-path molecular distillation has the advantage of reducing the distillation temperature, as the distillation is carried out under a high vacuum, and of also reducing the residence time of the mixture to be separated in the
still. The rate of decomposition of the products increases enormously as a function of the temperature and of the exposure time and, in a still of "alembic" type, for example, the mixtures may remain at high temperatures for hours, which results in denaturation.
Until now, in the case of vegetable oils, such a process had been used only to isolate unsaponifiable fractions or to purify the same vegetable oils by removing the unsaponifiable fractions or also, in the case of water- soluble or fat-soluble fractions, to decolor or deodorize the extracts.
In point of fact, it has now been found that, surprisingly, the use of a molecular distillation stage made it possible to isolate an oily fraction from a fat-soluble extract in which this oily fraction is present in a minor amount.
Preferred conditions for implementation of the process are given below:
Advantageously, before the distillation, a heavy solvent chosen from mineral or vegetable oils and polyols, such as, for example, polyethylene glycol, is added to the Magnolia champaca concrete obtained after extraction and optionally fractionation, in order to facilitate the distillation or the flow along the column.
The mixture of the concrete obtained after extraction and optionally fractionation and of the heavy solvent is introduced at a constant flow rate, at a temperature of between 20 and 1200C, preferably between 50 and 1000C, onto the hot wall of a cylindrical evaporator.
It is spread, by wiping using rotating annular wipers, as a thin film over the entire surface of the hot wall
maintained at a temperature between approximately 100 and 2000C and preferably between 110 and 170°C.
On contact with the latter, and under the very low pressure prevailing in the evaporator, of the order of 10 mbar to 0.001 mbar, the volatile product is then partially and gradually evaporated while the less volatile product flows along the wall.
The vapors given off are condensed on the cold wall concentric with the hot wall and placed a very short distance from the latter, preferably at a temperature of between 40 and 1200C, in particular between 60 and 1000C.
The products separated during operation flow by gravity along the hot and cold walls.
The distillate is recovered and is subjected, if appropriate, to an additional separation operation (filtration or centrifuging, for example) .
A Magnolia champaca oil according to the invention is thus obtained.
Advantageously, said oil is light in color. Furthermore, said oil is devoid of solvent or of any other chemical reactant which was involved during its extraction.
Also, said oil is provided in a sufficiently concentrated form to be able to be used without causing the formulation problems normally related to the concentrations necessary in order to obtain an activity in the cosmetic, pharmaceutical or dermatological compositions in the emulsion form and without exhibiting a dark color, contrary to the plant extracts obtained by standard processes, when they are in the concentrated form.
For this reason, the oil according to the invention can be used directly for the preparation of a cosmetic, pharmaceutical or dermatological composition.
The invention also relates to the Magnolia champaca oil capable of being obtained by the process described above.
According to a subsequent aspect, the invention relates to the use of a Magnolia champaca oil as described above as polyfunctional active agent in a cosmetic, pharmaceutical or dermatological composition for the prevention and/or treatment of detrimental changes in the skin due to aging or to physiological mechanisms related to aging or to disorders connected with these mechanisms.
In particular, the invention relates to the use of a Magnolia champaca oil as described above in a cosmetic composition as agent which improves healing or cell repair and/or agent for activating the metabolism of the cells of the epidermis and/or agent for scavenging free radicals and/or agent for detoxifying the epidermis.
The invention also relates to the use of a Magnolia champaca oil as described above as agent which improves healing or cell repair and/or agent for activating the metabolism of the cells of the epidermis and/or agent for scavenging free radicals and/or agent for protecting nuclear DNA and/or agent for protecting mitochondrial DNA and/or agent for detoxifying the epidermis, for the preparation of a pharmaceutical or dermatological composition.
This is because, advantageously, it has been found that the Magnolia champaca extract according to the invention had several advantageous activities with regard to preventative or repairing physiological mechanisms related to the detrimental changes in the skin due in particular to aging.
The invention thus relates more particularly to the use of a Magnolia champaca oil as described above as agent which inhibits the synthesis of melanin, in particular as agent which inhibits the synthesis of endothelin, in a cosmetic, pharmaceutical or dermatological composition. Endothelin is a messenger protein which promotes the proliferation of the melanocytes and the increase in melanogenesis responsible for the pigmentation of the skin related to aging ("liver spots") .
The invention relates in particular to the use of a Magnolia champaca oil as described above as agent which inhibits the transcription factor MITF (Microphthalmia- associated Transcription Factor) , a factor for regulating and differentiating melanocytes, in a cosmetic or dermatological composition.
It has also been found that, advantageously, the Magnolia champaca oil according to the invention stimulates the synthesis of several families of growth factors by keratinocytes .
In particular, this activity is exerted with regard to the following growth factors:
PDGF or platelet-derived growth factor, which exerts in particular a mitogenic activity on the majority of the cells derived from the mesenchyme (Lepisto J. et al . , 1995, Biochem. Biophys . Res. Commun., 209(2), 393-9) and stimulates the synthesis of collagen and collagenase by these cells, thus playing a role in physiological processes, such as healing and tissue repair (Tan E. M. et al., Biochem. J., 1995, 310 (Pt 2), 585-8); it has also been shown that the level of induction of PDGFs and the replicative capacity of cells were related to age: senescent fibroblasts have their level of PDGF, which
decreases (Karlsson C. et al . , J. Cell Physiol., 1994, 158(2), 256-62). Also, it has been shown that the amount and the type of the various growth factors could explain the differences in the ability of tissues to repair themselves with age (Ashcroft G. S. et al . , J. Anat., 190, 1997 (Pt 3) , 351-65) .
VEGF or vascular endothelial growth factor, which represents, in the skin, a major skin angiogenesis factor. The epidermis is an important source of VEGF, secreted in large amounts by proliferating keratinocytes . The mRNA of VEGF is expressed by normal keratinocytes, both in the tissue in situ and in cell culture. It has been shown that VEGF would maintain the homeostasis of endothelial cells and their ability to respond to an angiogenic stimulation, even in elderly subjects (Watanabe Y. et al . , 1997, Oncogene, 14, 2025- 2032) .
Moreover, a decrease in VEGF has been observed following exposure to UV radiation (Mildner M. et al., Photochem. Photobiol., 1999, 70(4), 674-9).
HB-EGF or heparin-binding epidermal growth factor, which plays an important role in the regulation and differentiation of keratinocytes (Iwamoto et al., Cytokine and Growth Factors Reviews, 2000, 11, 335-344) and in the senescence of young cells, the growth of which depends on this factor (JID Suppl., 24, S46-S50; Kanzaki Y. et al., Exp. Cell. Res., 2002, 279(2), 321- 329) .
The term "activator of the synthesis of several families of growth factors" is understood to mean, according to the invention, any molecule capable of stimulating the activity and/or the expression and/or the release of at least one of
these growth factors expressed and/or synthesized by and in keratinocytes .
The invention thus relates to the use of a Magnolia champaca oil as described above as agent which activates the synthesis of at least one cell growth factor by keratinocytes, in particular as agent which activates at least one growth factor chosen from PDGF, VEGF and HB-EGF, in a cosmetic, pharmaceutical or dermatological composition.
The invention also relates to the use of a Magnolia champaca oil as described above as agent which inhibits the activity of the enzymes involved in the degradation of the matrix, in particular matrix metalloproteinases (MMPs) and very particularly MMP3 (or stromelysin 1) and MMP9 (or gelatinase B) .
Matrix metalloproteinases are enzymes (endoproteases) which degrade the extracellular matrix in the context of the physiological remodeling of the skin. Age and exposure to
UV irradiation of A and/or B type have the consequence of increasing activity of these MMPs, in particular that of
MMP3 (or stromelysin 1) and of MMP9 (or gelatinase B) , and this increase contributes, with the slowdown in cell growth, to chronological aging of the skin (WO 98/36742) .
For this reason, the extracellular matrix is degraded to an increased extent, with as a result the sagging of the tissues of the skin and the formation of wrinkles (Rittie L. et al., Ageing Res. Rev., 2002, 1(4), 705-20; Chung J. H. et al., J. Invest. Dermatol., 2001, 117(5), 1218-24).
The term "metalloproteinase inhibitor" is understood to mean, according to the invention, any molecule capable of inhibiting the activity and/or the expression and/or the release of at least one of the metalloproteinases expressed and/or synthesized by and in the skin.
The invention also relates, according to preferred aspects, to the use, as antioxidant, of a Magnolia champaca oil as described above in a cosmetic composition or for the preparation of a pharmaceutical or dermatological composition.
The invention also relates, according to preferred aspects, to the use, as agent which stimulates the cell metabolism, of a Magnolia champaca oil as described above in a cosmetic composition or for the preparation of a pharmaceutical or dermatological composition.
The invention also relates, according to preferred aspects, to the use, as agent for detoxifying the epidermis as a result of oxidative stress, in particular by stimulating the synthesis of DT diaphorase (NQOl) , which catalyzes the detoxification of quinones, and also by stimulating the synthesis of glutathione S-transferase, which catalyzes the detoxification of chemical metabolites, such as lipid peroxidation products, of a Magnolia champaca oil as described above in a cosmetic composition or for the preparation of a pharmaceutical or dermatological composition.
The invention also relates, according to another preferred aspect, to the use, as agent which stimulates cellular energy, in particular cytochrome C and AMP kinase, of a Magnolia champaca oil as described above in a cosmetic composition or for the preparation of a pharmaceutical or dermatological composition.
Cytochrome C oxidase, the final stage in the electron transport chain, is crucial for cellular respiration and also contributes to the synthesis of cellular ATP (Lalla A. et al., West Indian Med. J., 2001, June, 50(2), 111-6). The energy status of the cell is coordinated by the AMP-
activated protein kinase (AMPK) system and also contributes to the ATP content of the cell (Dagon Y. et al., J. Biol. Chem., 2005, 23, 280(51), 42142-8).
The invention also relates, according to a subsequent aspect, to a cosmetic composition or a pharmaceutical or dermatological composition comprising a Magnolia champaca oil as described above and a cosmetically or pharmaceutically acceptable vehicle.
Preferably, said extract is present in the cosmetic, pharmaceutical or dermatological composition in a proportion of 0.001 to 10% by total weight of the composition, in particular in a proportion of 0.01 to 5%, preferably of 0.1 to 1%, by total weight of the composition.
Said cosmetic, pharmaceutical or dermatological composition can in particular be appropriate for application by the topical route.
Advantageously, said cosmetic, pharmaceutical or dermatological composition can be provided in the form of a powder, of an emulsion, of a microemulsion, of a nanoemulsion, of a suspension, of a solution, of a lotion, of a cream, of an aqueous or aqueous/alcoholic gel, of a foam, of a serum, of an aerosol solution or dispersion or of a dispersion of lipid vesicles.
In the case of an emulsion, it can be a water-in-oil or oil-in-water emulsion.
The cosmetic, pharmaceutical or dermatological composition according to the invention also comprises a solvent chosen according to the various ingredients and the administration form.
Mention may be made, by way of examples, of water (preferably demineralized water) , an alcohol, such as ethanol, or a diethylene glycol ether, such as ethoxydiglycol or diethylene glycol monomethyl ether.
Said cosmetic, pharmaceutical or dermatological composition can also comprise at least one additive conventional in the field, such as, for example, at least one compound chosen from an emollient or humectant, a gelling and/or thickening agent, a surface-active agent, an oil, an active agent, a dye, a preservative, an antioxidant, a chelating agent, an organic or inorganic powder, a pigment, a self-tanning agent, a sunscreen, an essential oil and a fragrance.
In particular, without limitation, said composition can comprise :
one or more humectant (s) chosen, for example, from polyols, such as glycerol, propylene glycol, butylene glycol, polyethylene glycol, sugars or their derivatives, urea, glycolic acid or its salts, lactic acid or its salts, or hyaluronic acid.
Said humectant will be present in the composition at a content of the order of 0.01 to 20%, preferably 0.5 to 10%, by total weight of the composition.
One or more emollient (s) chosen, for example, from volatile or nonvolatile silicones (dimethicone, cyclomethicone, dimethiconol, and the like) , long-chain hydrocarbons, or esters of fatty acids or of fatty alcohols .
Said emollient will be present in the composition at a content of the order of 0.5 to 30%, preferably 0.5 to 15%, by total weight of the composition.
One or more gelling and/or thickening agent (s), preferably one or more hydrophilic gelling agents, for example chosen from cellulose derivatives, gums of vegetable origin (guar, locust bean, alginates, carrageenans, pectin), gums of microbial origin (xanthan) , clays (laponite) , carboxyvinyl polymers (carbomer) , acrylic copolymers, such as acrylate/alkyl- arylate copolymers, polyacrylamides, ammonium acryloyl- dimethyltaurate copolymers, such as ammonium acryloyldimethyltaurate/vinylpyrrolidone (VP) copolymer and ammonium acryloyldimethyltaurate/beheneth-25 methacrylate copolymer (such as, for example, those sold under the names Aristoflex AVC and HMB by Clariant) .
Non-film-forming gelling agents can, for example, be chosen from clays (laponite) , ammonium acryloyldimethyltaurate/VP copolymer and ammonium acryloyldimethyltaurate/beheneth-25 methacrylate copolymer (such as, for example, those sold under the names Aristoflex AVC and HMB by Clariant) .
Said gelling and/or thickening agent will be present in the composition at a content of the order of 0 to 10% by total weight of the composition, preferably 0.1 to 5% by total weight of the composition.
One or more surface-active agent (s) or cosurfactant (s) , preferably nonionic, present in a content of the order of 0.01 to 10%, preferably 0.1 to 5%, by total weight of the composition.
One or more fatty substances which is (are) liquid or solid at ambient temperature, commonly referred to as oil(s), which may be volatile or nonvolatile, which may be hydrocarbon- or silicone-based and which may be linear, cyclic or branched, or butter (s), for example isododecane, cyclopentadimethylsiloxane, dimethicone, isononyl isononanoate, pentaerythrityl tetraisostearate,
triglycerides of caprylic and capric acid, shea butter, and the like, preferably in a proportion of 0.01 to approximately 15%, preferably 0.1 to 10%, by total weight of the composition.
One or more active agent (s) of natural, biotechnological or synthetic origin having a biological activity and having an effectiveness on the skin via biological sites, for example chosen from vitamins, trace elements, allantoin, plant proteins, plant extracts, and the like. In particular, said active agent can be an algal extract .
One or more water-soluble dye(s), such as, for example, the disodium salt of ponceau, the disodium salt of alizarin green, quinoline yellow, the trisodium salt of amaranth, the disodium salt of tartrazine, the monosodium salt of rhodamine, the disodium salt of fuchsin, or xanthophyll, preferably in a proportion of 0 to approximately 2% by total weight of the composition.
Other additives normally used in the cosmetics, pharmaceutical or dermatological fields can also be present in the composition according to the invention, in particular preservatives, chelating agents, antioxidants, essential oils or fragrances well known in the technical field.
A person skilled in the art is in a position to choose, among all these possible additives, both the composition and the amount of those which will be added to the composition so that the latter retains all of its properties .
The invention is illustrated without implied limitation by the following examples.
Example 1: Process for the preparation of a Magnolia champaca oil according to the invention
1) Hexane extraction
200 kg of fresh Magnolia champaca flowers are charged to a 1000 1 reactor.
800 1 of hexane are added and heating is carried out at 35°C for 40 min.
The reactor is emptied of the hexane solution. The charged solvent is retained.
600 1 of hexane are again charged to the reactor. Heating is carried out at 35°C for 40 min.
The hexane solution is again emptied. The two filtrates are combined.
The hexane is evaporated.
0.56 kg of Magnolia champaca concrete is thus recovered.
Yield: 0.28%
2) Molecular distillation
303 g of the concrete are mixed with 130 g of polyethylene glycol 600 (INCI name: PEG 12) :
Two passes through a distillation apparatus of KDL4 type (UIC GmH) are carried out according to the following distillation parameters:
The yields of the distillation are as follows, expressed with regard to the weight of starting material:
Distillate, 1st pass = 25.7% Distillate, 2nd pass = 31.34%
3) Mixing
After combining and homogenizing the two distillates, a mixture is produced with propylene glycol: 90% by weight of propylene glycol with 10% by weight of the distillate. The mixture is homogenized and filtered through a 25 μm filter. The filtrate is recovered.
1640 g of Magnolia champaca oil are obtained.
Example 2: Analysis of the composition of a Magnolia champaca oil according to the invention
100 mg of extract obtained during stage 3 of the process described in Example 1 are dissolved in 2 ml of a IN methanolic hydrochloric acid solution. The solution is placed, after stirring, in a waterbath at 80°C for 10 min.
The sample thus esterified is recovered by liquid/liquid extraction with 2 ml of heptane and injected in gas chromatography.
Chromatography is carried out under the following conditions :
Gas chromatograph (Agilent series 6890) . Injector, with or without division at 2500C.
Injection of 0.5 μl of sample prepared with a division of 1/lOOth.
Separation on a 100% grafted polydimethylsiloxane capillary column, length 30 m, internal diameter 0.25 mm, film thickness: 0.25 μm (Agilent series DB-I).
Carrier gas: helium at 1 ml/min.
Initial temperature of the column oven: 7O0C. Temperature gradient from 70 °C to 250 °C at 2°C/minute and isotherm at 2500C for 60 min.
Total time: 120 min.
Detection: flame ionization detector (auxiliary gas nitrogen) .
The percentages given in table 1 below are expressed as relative percentages obtained by the integrator of the chromatograph. Only the compounds which can vaporize in the injector are present in these results. The propylene glycol has not been integrated and is thus not listed in the table below.
The constituents were identified by mass spectrometry.
The results are given in table 1 below.
Table 1
Example 3: Study of the activity of Magnolia champaca oil according to the invention with regard to the growth factor HB-EGF
A sample of Magnolia champaca oil obtained in example 1, diluted beforehand to 10% in propylene glycol, was tested at different concentrations.
1) Preparation of keratinocyte cultures
This protocol is common to all the biological activity assays.
Keratinocytes derived from neonatal foreskins (Clonetics,
San Diego, USA) were seeded into β-well plates and cultured in culture medium for keratinocyte growth (KBM, Clonetics) , namely a modified culture medium supplemented with
recombinant human EGF, insulin, hydrocortisone, bovine pituitary extract, gentamycin and amphotericin B.
After culturing for 24 h in an incubator at 37°C, 5% CO2 and with saturated humidity, the cells are washed with PBS buffer pH 7.4 (Gibco) and incubated with specific basic medium (KBM, Clonetics) comprising the products to be tested, for 6 h or 24 h according to the tests, at different concentrations.
Each concentration was tested in triplicate on two donors for the "ELISA" and "Western Blot" tests and in duplicate on two donors for the molecular biology tests.
A control without product to be tested ("untreated") is also carried out by keeping the cells in the same medium without treatment .
A positive control is optionally carried out with a reference product for the activity tested.
2) Measurement of the HB-EGF messenger RNA (mRNA) expression
Principle of the assay
The real-time polymerase chain reaction (RT-PCR) is used to quantify the expression of the HB-EGF messenger RNA in a treated sample in comparison with an untreated sample. The results are normalized with respect to the expression of housekeeping genes in these samples and corrected as regards the differences in PCR efficiency.
The results are expressed as number of times the target gene (HB-EGF) expression is increased or decreased in the treated sample, and not as absolute number of copies.
The sequences of the cDNAs/mRNAs of the genes investigated were obtained from GenBank.
Target gene: HB-EGF Housekeeping gene: PBDG
All the PCR primers were obtained using the PRIMER3 software from the Whitehead Institute for Biomedical Research.
Assay protocol:
The mRNA was isolated using the Trizol reagent (Invitrogen) according to the manufacturer's recommendations. The reverse transcription was carried out using the GeneAmp RNA PCR kit (Applied Biosystems) according to the manufacturer's recommendations.
The real-time PCR measurement was carried out using the LightCycler technology (Roche Applied Science) with SYBR
Green I detection. In all the assays, the cDNA was amplified using a standardized program. Each LightCycler capillary was charged with 1.5 μl of DNA Master mix, 1.8 μl of MgCl2 (25 mM) , 10.1 μl of water and 0.5 μl of each primer (10 μM stock) . The final amount of cDNA per reaction corresponded to 25 ng of total RNA used for the reverse transcription .
The specificity of the PCR was tested by agarose gel electrophoresis and sequencing, and was evaluated for each sample using a melting point analysis included in the PCR program.
The relative quantification of the target gene expression was carried out using the Pfaffl mathematical model (Pfaffl, M. W., Nucleic Acids, Res., 29(9), p. E45, 2001).
The results are given in table 2 below.
Use was made, as positive control, of tumor necrosis factor α (TNFα) , which is an antiinflammatory cytokine known to stimulate HB-EGF.
Table 2
The results show that the Magnolia champaca oil according to the invention has a stimulatory activity with respect to the synthesis of HB-EGF mRNA.
Example 4 : Study of the activity of Magnolia champaca oil according to the invention with regard to the growth factor VEGF
The measurement was carried out by RT-PCR in the same way as in example 3. The sequences of the cDNAs/mRNAs of the genes investigated were obtained from GenBank.
Target gene: VEGF
Housekeeping gene: β2-microglobulin
The keratinocyte culture conditions are as described in example 3.
The results are reported in table 3 below:
Table 3
The results show that the Magnolia champaca oil according to the invention has a stimulatory activity with respect to the synthesis of VEGF mRNA.
Example 5: Study of the activity of Magnolia champaca oil according to the invention with regard to the growth factor PDGF-AA
The quantitative evaluation of the concentrations of human PDGF-AA growth factor in the cell cultures was carried out using the ELISA method by employing the Quantikine® immunological assay kit (No. DAA00, R&D Systems) .
The keratinocyte culture conditions and the samples tested are as described in example 3.
The results are reported in Table 4 below;
Table 4
Concentration (%) % PDGF-AA activity
0 (untreated control) 100
0 01% 230 15
0 005% 307 2
The results show that the Magnolia champaca oil according to the invention has a stimulatory activity with respect to the synthesis of PDGF-AA.
Example 6: Study of the activity of Magnolia champaca oil according to the invention with regard to endothelin-1
The quantitative evaluation of the concentrations of human endothelin-1 in the cell cultures was carried out using the ELISA method by employing the Quantikine® immunological assay kit (No. BBE5, R&D Systems) .
The keratinocyte culture conditions and the samples tested are as described in example 3.
The results are reported in table 5 below:
Table 5
The results show that the Magnolia champaca oil according to the invention has an inhibitory activity with respect to the synthesis of endothelin-1.
Example 7: Study of the activity of Magnolia champaca oil according to the invention with regard to MITF
The quantitative evaluation of the concentrations of MITF mRNA in the cell cultures was carried out according to the protocol described in example 3.
Target gene: MITF
Housekeeping gene: β2-microglobulin
Kojic acid was used as positive control for the inhibition. The results are reported in table 6 below.
Table 6
The results show that the Magnolia champaca oil according to the invention has an inhibitory activity with respect to the expression of MITF mRNA.
Example 8 : Study of the activity of Magnolia champaca oil according to the invention with regard to matrix πietalloproteinases (MMPs)
1/ Principle of the assay
The products to be tested are incubated with the activated MMPs. The enzymatic activity is controlled by the addition of a fluorescent enzymatic substrate specific for each MMP.
2/ Assay protocol
Pro-MMP3 or pro-MMP9 are incubated in plates with a 1 mM APMA (p-aminophenylmercuric acetate) solution at ambient temperature, with gentle stirring, for 1 h.
Various concentrations of the various potential inhibitors are added. The mixture is subsequently incubated at ambient temperature with gentle stirring. The enzymatic reaction is initiated by adding the fluorescent substrate (SIGMA) dissolved in DMSO.
The enzymatic reaction is monitored for 1 h using a spectrofluorimeter and the fluorescence is measured at an excitation wavelength of 360 nm and an emission wavelength
of 460 nm for MMP3 (or stromelysin 1) and at an excitation wavelength of 320 nm and an emission wavelength of 405 nm for MMP9 (or gelatinase B) .
The results are expressed in units of fluorescence emitted (RFU) , which represents the amount of substrate hydrolyzed per min.
The Microwin 2000 spectrofluorimeter calculates the variation in absorbance Δ, which represents the initial rate (Vi) of the enzymatic reaction. In each assay, the mean of the 3 values of Vi obtained for each concentration of potential inhibitor is calculated. The results of 10 experiments were expressed as mean ± SD and then presented as percentage of residual activity.
The results are reported in tables 7 (MMP3 or stromelysin 1) and 8 (MMP9 or gelatinase B) below.
Use was made, as positive control, of ethylenediamine- tetraacetic acid (EDTA) , which has a well known inhibitory activity with respect to the class of the metalloproteinases .
Table 7
Table 8
The results show that the Magnolia champaca oil according to the invention inhibits the activity of the matrix metalloproteinases MMP3 and MMP9.
Example 9: Study of the activity of Magnolia champaca oil according to the invention with regard to the synthesis of DT diaphorase
After having prepared the cells according to the protocol of example 3, the cells are lyzed for their analysis by Western blotting. After the quantification of the proteins according to the kit (Pierce Chemical Co., NY), the proteins are fractionated on a gel gradient. The polyvinylidene difluoride (PVDF) membranes resulting from the transfer from the gels are incubated in the presence of an anti-NQOl polyclonal antibody (Genetex, San Antonia, TX) . After rinsing, the membranes are developed by a "Supersignal West Dura" detection kit (Pierce Chemical Co., NY) and the bands are quantified by image analysis.
The results are reported in table 9 below:
Table 9
Concentration (%) % DT diaphorase activity
0 (untreated control) 100
0 02% 176
0 04% 213
The results show that the Magnolia champaca oil according to the invention stimulates the activity of DT diaphorase.
Example 10: Study of the activity of Magnolia champaca oil according to the invention with regard to the synthesis of glutathione S-transferase (GST)
After having prepared the cells according to the protocol of example 3, the cells are lyzed and the supernatants recovered. The activity of GST is evaluated by the use of the "GST Activity Assay Kit" (Biodivision, Mountain View, CA) according to the protocol described by the supplier of the kit .
The results are reported in table 10 below:
Table 10
The results show that the Magnolia charnpaca oil according to the invention stimulates the synthesis of glutathione S- transferase .
Example 11: Study of the activity of Magnolia champaca oil according to the invention with regard to the synthesis of cellular cytochrome C
The amount of cytochrome C in the lysates of the keratinocytes prepared according to the protocol of example 3 is quantified with the "Cytochrome C ELISA Kit" (Zymed®) .
The results are reported in table 11 below:
Table 11
The results show that the Magnolia champaca oil according to the invention stimulates the synthesis of cellular cytochrome C.
Example 12: Study of the activity of Magnolia champaca oil according to the invention with regard to the synthesis of AMP kinase
After having prepared the cells according to the protocol of example 3, the cells are lyzed for their analysis by
Western blotting. After the quantification of proteins according to the kit (Pierce Chemical Co., NY), the proteins are fractionated on a gel gradient. The membranes resulting from the transfer from the gels to the membrane (PVDF) are incubated in the presence of an anti-AMPK or anti-phospho-AMPK α monoclonal antibody (Cell Signaling
Technology, Beverly, MA) . After rinsing, the membranes are developed by the "Supersignal West Dura" detection kit
(Pierce Chemical Co., NY) and the bands are quantified by image analysis.
The results are reported in table 12 below:
Table 12
The results show that the Magnolia champaca oil according to the invention has a stimulatory activity with respect to the synthesis of AMP kinase.
Example 13: Study of the antioxidant activity of Magnolia champaca oil according to the invention
Principle of the three protocols
The various Abel" 1 antioxidant test kits (Knight Scientific Limited) make it possible to measure the ability of a sample to block free radicals. In each experiment, a particular type of radical or oxidant is generated: hydroxyl radical, halogenated oxidants or superoxide radical. These chemoluminescent tests comprise a special Pholasin® photoprotein which emits light in the presence of free radicals and of certain oxidants. The antioxidant capacity of the sample is expressed by the percentage of reduction in the luminescent peak of the Pholasin" observed during the time of the various tests in the presence or in the absence of the sample or of the controls.
A positive control was employed for each of the studies a, b and c below.
a/ Study of the activity of Magnolia champaca oil according to the invention with regard to inhibition of the hydroxyl radical
Use was made, as positive control, of mannitol, which exhibits known effects in combating free radicals with regard to the hydroxyl radical.
Table 13
The results show that the Magnolia champaca oil according to the invention has an antioxidant activity with regard to the hydroxyl radical.
b/ Study of the activity of Magnolia champaca oil according to the invention with regard to the inhibition of halogenated oxidants
Use was made, as positive control, of bovine serum albumin (BSA) , which exhibits a known inhibitory activity with regard to halogenated oxidants.
Table 14
The results show that the Magnolia champaca oil according to the invention has an antioxidant activity with regard to halogenated oxidants.
c/ Study of the activity of Magnolia champaca oil according to the invention with regard to the inhibition of the superoxide radical
Use was made, as positive control, of vitamin C (ascorbic acid) . Ascorbic acid is well known for its role in the formation of superoxide radicals.
Table 15
The results show that the Magnolia champaca oil according to the invention has an antioxidant activity with regard to the superoxide radical.
Example 14: Eye contour cream comprising a Magnolia champaca oil according to the invention
The various ingredients mentioned in the following tables 16 and 17 are designated by their normal chemical name or according to the INCI international nomenclature (International Cosmetic Ingredient Dictionary and Handbook published by The Cosmetic, Toiletry and Fragrance Association, 9th Edition, 2002) .
Table 16
Table 17
Claims
1. Oil extracted from flowers of at least one type of Magnolia champaca, characterized in that it comprises:
20 to 70% of benzoic ester,
15 to 35% of saturated and/or unsaturated fatty acids,
said proportions being expressed as relative percentages with respect to the combined constituents separated by gas chromatography.
2. Oil according to Claim 1, characterized in that it originates from Magnolia champaca, variety gold.
3. Oil according to Claim 1 or 2, characterized in that it comprises:
- from 10 to 40% of cinnamyl benzoate, from 5 to 30% of phenylethyl benzoate, from 5 to 30% of benzyl benzoate, from 5 to 30% of linoleic acid, from 2 to 20% of linolenic acid,
said proportions being expressed as relative percentages with respect to the combined constituents separated by gas chromatography .
4. Oil according to any one of Claims 1 to 3, characterized in that it is devoid of solvent.
5. Oil according to any one of Claims 1 to 4, characterized in that it is devoid of chemical reactant which was involved during its extraction.
6. Process for the preparation of a Magnolia champaca oil according to any one of Claims 1 to 5, characterized in that it "comprises at least one molecular distillation stage .
7. Process for the preparation of a Magnolia champaca oil according to any one of Claims 1 to 5, characterized in that it comprises the stages consisting in:
- extracting from a milled product produced from fresh flowers of at least one type of Magnolia champaca using at least one nonpolar solvent,
subjecting said extract to at least one molecular distillation stage, and
recovering the distillate.
8. Process according to Claim 7, characterized in that said nonpolar solvent is chosen from hexane, cyclohexane, heptane, isooctane, supercritical CO2 or dichloromethane .
9. Process according to any one of Claims 6 to 8, characterized in that the molecular distillation stage is carried out at a temperature of between approximately 100 and 2000C and at a pressure of between approximately 10 and 0.001 mbar.
10. Process according to any one of Claims 7 to 9, characterized in that, on conclusion of the extraction, the fractionation is carried out using at least one solvent chosen from Ci-C4 alcohols, polyols, ethyl acetate, hexane, cyclohexane and supercritical CO2.
11. Process according to any one of Claims 6 to 10, characterized in that, prior to the molecular distillation, a solvent chosen from mineral or vegetable oils and polyols is added.
12. Process according to any one of Claims 6 to 11, characterized in that the temperature for introducing into the distillation column is between 20 and 1200C, preferably between 50 and 1000C.
13. Process according to any one of Claims 6 to 12, characterized in that the condensation temperature is between 40 and 1200C, preferably between 60 and 1000C.
14. Magnolia champaca oil capable of being obtained by the process according to any one of Claims 6 to 13.
15. Use of a Magnolia champaca oil according to any one of Claims 1 to 5 or 14 as polyfunctional active agent in a pharmaceutical, cosmetic or dermatological composition for the prevention and/or treatment of detrimental changes in the skin due to aging or to physiological" mechanisms related to aging or to disorders connected with these mechanisms .
16. Use according to Claim 15 of a Magnolia champaca oil according to any one of Claims 1 to 5 or 14 in a cosmetic composition as agent which improves healing or cell repair and/or agent for activating the metabolism of the cells of the epidermis and/or agent for scavenging free radicals and/or agent for regenerating the epidermis and/or agent for detoxifying the epidermis.
17. Use according to Claim 15 of a Magnolia champaca oil according to any one of Claims 1 to 5 or 14 as agent which improves healing or cell repair and/or agent for activating the metabolism of the cells of the epidermis and/or agent for scavenging free radicals and/or agent for protecting nuclear DNA and/or agent for protecting mitochondrial DNA and/or agent for regenerating the epidermis and/or agent for detoxifying the epidermis, for the preparation of a pharmaceutical composition.
18. Use according to Claim 15 of a Magnolia champaca oil according to any one of Claims 1 to 5 or 14 as agent which improves healing or cell repair and/or agent for activating the metabolism of the cells of the epidermis and/or agent for scavenging free radicals and/or agent for protecting nuclear DNA and/or agent for protecting mitochondrial DNA and/or agent for regenerating the epidermis and/or agent for detoxifying the epidermis, for the preparation of a dermatological composition.
19. Use according to any one of Claims 15 to 18 of a Magnolia champaca oil as agent which inhibits the synthesis of melanin.
20. Use according to any one of Claims 15 to 19 of a Magnolia champaca oil as agent which inhibits the synthesis of endothelin or agent which inhibits the transcription factor MITF.
21. Use according to any one of Claims 15 to 19 of a Magnolia champaca oil as agent which activates the synthesis of at least one cell growth factor by keratinocytes .
22. Use according to Claim 21, characterized in that said growth factor is chosen from PDGF, VEGF and HB-EGF.
23. Use according to any one of Claims 15 to 18 of a Magnolia champaca oil as agent which inhibits the activity of the matrix metalloproteinases MMP3 (or stromelysin 1) and MMP9 (or gelatinase-elastase B) .
24. Use according to any one of Claims 15 to 18 of a Magnolia champaca oil as an agent which stimulates the cell metabolism.
25. Use according to Claim 24, characterized in that said factor for stimulating the cell metabolism is chosen from cytochrome C or AMP kinase.
26. Use according to any one of Claims 15 to 18 of a Magnolia champaca oil as antioxidant.
27. Use according to any one of Claims 15 to 18 of a Magnolia champaca oil as agent for detoxifying the epidermis by stimulating the synthesis of DT diaphorase.
28. Cosmetic, pharmaceutical or dermatological composition, characterized in that it comprises a Magnolia champaca oil according to any one of Claims 1 to 5 or 14 and a cosmetically or pharmaceutically acceptable vehicle.
29. Cosmetic, pharmaceutical or dermatological composition according to Claim 28, characterized in that said oil is present in the pharmaceutical, cosmetic or dermatological composition in a proportion of 0.001 to 10% by total weight of the composition.
30. Cosmetic, pharmaceutical or dermatological composition according to Claim 29, characterized in that said oil is present in the pharmaceutical, cosmetic or dermatological composition in a proportion of 0.01 to 5%, preferably of 0.1 to 1%, by total weight of the composition.
31. Cosmetic, pharmaceutical or dermatological composition according to any one of Claims 28 to 30, characterized in that it is appropriate for application by the topical route.
32. Cosmetic, pharmaceutical or dermatological composition according to any one of Claims 28 to 31, characterized in that it also comprises at least one compound chosen from an emollient or humectant, a gelling and/or thickening agent, a surface-active agent, an oil, an active agent, a dye, a preservative, an antioxidant, a chelating agent, an organic or inorganic powder, a pigment, a self-tanning agent, a sunscreen, an essential oil and a fragrance.
33. Cosmetic, pharmaceutical or dermatological composition according to Claim 32, characterized in that it comprises an active agent of natural, biotechnological or synthetic origin having a biological activity and having an effectiveness on the skin via biological sites.
34. Cosmetic, pharmaceutical or dermatological composition according to either of Claims 32 and 33, characterized in that said active agent is chosen from vitamins, trace elements, allantoin, plant proteins, plant extracts and their mixtures.
35. Cosmetic, pharmaceutical or dermatological composition according to one of Claims 32 to 34, characterized in that said active agent is an algal extract.
36. Cosmetic, pharmaceutical or dermatological composition according to any one of Claims 28 to 35, characterized in that it is provided in the form of a powder, of an emulsion, of a microemulsion, of a nanoemulsion, of a suspension, of a solution, of a lotion, of a cream, of an aqueous or aqueous/alcoholic gel, of a foam, of a serum, of an aerosol solution or dispersion or of a dispersion of lipid vesicles.
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DE102012211807A1 (en) * | 2012-07-06 | 2014-01-09 | Beiersdorf Ag | Combination of extracts of magnolia bark extract and hyaluronic acid and their cosmetic and / or dermatological use |
WO2013154899A3 (en) * | 2012-04-10 | 2014-01-30 | The Procter & Gamble Company | Malodor reduction compositions |
US9399078B2 (en) | 2009-12-17 | 2016-07-26 | The Procter & Gamble Company | Unscented and low scented malodor control compositions and methods thereof |
CN106860118A (en) * | 2017-03-25 | 2017-06-20 | 广州市聚吉科绿色化学共性技术研究院有限公司 | A kind of anti-aging face cream |
US9861604B2 (en) | 2012-04-11 | 2018-01-09 | Bagi Research Limited | Coriolus versicolor extracts, methods of isolating biologically-active compounds, and uses thereof |
US11110196B2 (en) | 2013-08-01 | 2021-09-07 | The Procter & Gamble Company | Articles comprising malodor reduction compositions |
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JP6182728B2 (en) * | 2012-11-02 | 2017-08-23 | 国立大学法人名古屋大学 | Methods for evaluating efficacy and toxicity targeting stem cells |
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US9399078B2 (en) | 2009-12-17 | 2016-07-26 | The Procter & Gamble Company | Unscented and low scented malodor control compositions and methods thereof |
US9642927B2 (en) | 2009-12-17 | 2017-05-09 | The Procter & Gamble Company | Unscented and low scented malodor control compositions and methods thereof |
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DE102012211807A1 (en) * | 2012-07-06 | 2014-01-09 | Beiersdorf Ag | Combination of extracts of magnolia bark extract and hyaluronic acid and their cosmetic and / or dermatological use |
US9402801B2 (en) | 2012-07-06 | 2016-08-02 | Beiersdorf Ag | Active ingredient combinations of magnolia bark extract and hyaluronic acid and the cosmetic and/or dermatological use thereof |
US11110196B2 (en) | 2013-08-01 | 2021-09-07 | The Procter & Gamble Company | Articles comprising malodor reduction compositions |
CN106860118A (en) * | 2017-03-25 | 2017-06-20 | 广州市聚吉科绿色化学共性技术研究院有限公司 | A kind of anti-aging face cream |
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