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  • 专利说明
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    • 专利摘要:
    The present invention relates to the uses of swertiamarine or a swertiamarine enriched plant extract to stimulate the formation or regeneration of the epidermis and / or to stimulate the metabolism of the dermis mainly in the cosmetic field.
    公开号:FR3018191A1
    申请号:FR1451920
    申请日:2014-03-10
    公开日:2015-09-11
    发明作者:Carine Bezivin
    申请人:Lucas Meyer Cosmetics SAS；
    IPC主号:
    专利说明:

    [0001] FIELD OF THE INVENTION The present invention relates to the cosmetic field, in particular to cosmetic agents capable of stimulating the formation or regeneration of the skin. BACKGROUND OF THE INVENTION The skin is the first barrier protecting the body from external aggressions. This organ is composed of several layers of tissue. We distinguish the epidermis which is the outermost part of the skin, the dermis, a connective tissue consisting of fibroblasts and an extracellular matrix, which ensures the functions of cohesion and nutrition of the skin, and the hypoderm consists of of adipocytes. The epidermis consists of several cell layers of keratinocytes. There are, among others, the germinal layer of the epidermis, called the basal layer, containing, in particular, cutaneous stem cells, the spinous layer, Stratum spino, spm, consisting of several layers of polygonal cells, the granular layer, Stream granulosum , comprising one to three layers of flattened cells containing cytoplasmic inclusions, the keratohyalin grains, and finally, the stratum corneum Stratum corneuni which is composed of anucleate and keratin-rich cells called corneocytes which correspond to the terminal stage of differentiation of keratinocytes. The outermost cells of the stratum corneum are continually removed and replaced by the cells of a lower layer, according to a process called desquamation. Cellular regeneration of the stratum corneum is based on a cellular maturation process in which basal layer cells of the epidermis differentiate and migrate progressively through the different strata of the epidermis until they reach the stratum corneum under the form of corneocytes. Skin aging, whether it results from a normal phenomenon of senescence or is accentuated by an external factor such as exposure to UV radiation, involves dysfunctions of differentiation and / or cell renewal resulting in atrophy of all the foundations of the skin. From a histological point of view, there is, inter alia, a decrease in the quality of the dermis, in particular a loss of consistency of the extracellular matrix, and a decrease in the thickness of the epidermis.
    [0002] From an aesthetic point of view, these alterations result in a change in the appearance of the skin and its mechanical properties: the skin is less smooth, even rough, and can become dehydrated or dry. Its microrelief is more marked, and may have fine lines, which can lead over time to the formation of deep wrinkles. The skin may also have a loss of elasticity and firmness, and a less luminous complexion. The skin may have other alterations in its visual appearance, especially stretch marks or redness. There are many cosmetic products on the market for preventing or reducing wrinkles or reducing redness or stretch marks.
    [0003] Nevertheless, there remains, at present, a need for new active agents to prevent or treat skin alterations, in particular resulting from skin aging. SUMMARY OF THE INVENTION A first object according to the invention is the cosmetic use of swertiamarine or a plant extract enriched with swertiamarine to stimulate the formation or regeneration of the epidermis and / or to stimulate the metabolism of the dermis. Said swertiamarine or said plant extract may be used as an anti-redness, anti-aging or anti-wrinkle agent. The plant extract enriched with swertiamarine is preferably an extract obtained from a species of Swertia, such as Swertia chirata or Swertia milensis, and which comprises at least 90% by weight of swertiamarine. To this end, the swertiamarine or the plant extract is present, as active agent, in a composition, preferably a cosmetic composition, intended to be administered topically. Said composition is preferably intended to prevent or treat a sign of skin aging or stretch marks. It may also be intended to make less visible varicose vein, angioma or telangiectasia. Said composition may also be intended to prevent, treat or reduce redness or skin heating. The signs of skin aging include a thinning of the skin, especially the skin, the appearance of a microrelief, the appearance of fine lines and / or wrinkles on the skin, including the lips and eyelids , wilting or sagging of the skin, loss of radiance of the skin, dark circles, a cloudy complexion, loss of skin density, loss of firmness of the skin, loss of skin tone, a loss of elasticity of the skin, an alteration of the smooth appearance of the skin, and / or an increase in the roughness of the skin. In some embodiments, the composition is for treating or preventing transient or permanent redness, preferably in a skin type selected from the group consisting of sensitive skin, fragile skin, reactive skin, intolerant skin, skin with a tendency to have a rash, skin with an erythrosic tendency and skin with an erythro-rosacea tendency.
    [0004] The swertiamarine is generally from 0.0001% to 10% by weight, preferably from 0.001% to 5% by weight, more preferably from 0.005% to 0.5% by weight of the total weight of said composition. In some embodiments, said composition further comprises at least one additional cosmetic agent, preferably selected from the group consisting of vitamins, filters and sunscreens, anti-aging or anti-wrinkle agents, antioxidants, agents and the like. lifting agents, firming agents, anti-blemish agents, anti-redness agents, slimming agents, draining agents, moisturizing agents, soothing agents, exfoliating or exfoliating agents, mattifying agents, sebo-regulating agents, active ingredients lighteners, self-tanning actives, tanning accelerators and their combinations. In other embodiments, said composition may be in different forms. It can be chosen from the group consisting of aqueous solutions, hydro-alcoholic solutions, oil-in-water (O / W) or water-in-oil (W / O) emulsions or multiple (triple: W / O / E or H / E / H), nanoemulsions, in particular O / W nanoemulsions, whose drop size is less than 100 nm, aqueous gels, or dispersions of a fatty phase in an aqueous phase using spherules, suspensions, preferably in aqueous or hydroalcoholic media, liposome suspensions, powders, lotions, milks, creams, ointments, gels, mousses, and ointments.
    [0005] In particular embodiments, the composition is in the form of a cosmetic product, a makeup product or a personal hygiene product, for example a lotion, a milk, a serum or an aqueous gel. or oily, an emulsion, a cream, a cream-gel, a water of care, an ointment, a balm, a foundation, a spray, an eye shadow, a stick, a lipstick, a gloss, a The present invention also relates to the use of swertiamarine or a swertiamarine-enriched plant extract as a diuretic ingredient. The present invention also relates to the use of swertiamarine or a plant extract enriched with swertiamarine. healing agent or as a regenerative agent of the epidermis, in the treatment or prevention of damage to the skin or mucous membrane, in particular a cut, a burn, an erythema, an irritation, a blister, an blisters, cracks, micro-wounds, crack, crack, or splits illements. Said swertiamarine or said extract are preferably intended to be administered topically and, optionally, in combination with another active ingredient, preferably selected from the group consisting of soothing agents, moisturizing agents, anti-inflammatory agents, antioxidants, healing agents, disinfectants, antimicrobial agents (including antibiotic agents and antifungal agents) and combinations thereof.
    [0006] A further object according to the invention is the use of a pharmaceutical or cosmetic composition in the treatment of a lesion of the skin or mucosa, said composition comprising swertiamarine or a plant extract enriched with swertiamarine as healing agent or regenerative agent of the epidermis. Said composition may comprise from 0.0001% to 10% by weight, preferably from 0.001% to 5% by weight, more preferably between 0.005% and 0.5% by weight of swertiamarine. Said composition may further comprise an additional active ingredient preferably selected from the group consisting of soothing agents, moisturizing agents, anti-inflammatory agents, antioxidants, healing agents, disinfecting agents, antimicrobial agents and combinations thereof The plant extract enriched with swertiamarine may be an extract obtained from a species of Swertia, preferably Swertia chirata or Swertia milensis, and which comprises at least 90% by weight of swertiamarine.
    [0007] Finally, the subject of the invention is also a composition for the preparation of a pharmaceutical or cosmetic composition, comprising: from 0.1 to 20% of swertiamarine, said swertiamarine being preferably integrated in the form of a plant extract enriched with swertiamarine, in particular an extract obtained from a species of Swertia such as Swertia chirata or Swertia milensis, from 50% to 99.9% of a vehicle, preferably chosen from a filler, an aqueous solvent, a solvent organic, preferably a lower alcohol such as ethanol, propanediol, butylene glycol, glycerine or isopropanol, a lipophilic agent and mixtures thereof, and optionally, from 0.1 to 30% of an additional excipient pharmaceutically or cosmetically acceptable, preferably selected from a targeting agent, an antioxidant, a preservative, a stabilizing agent, a thickening agent, an emulsifier, a hydrophilic gelling agent or lipophilic, perfume, mineral or organic oil, and combinations thereof. This composition for the preparation of a pharmaceutical or cosmetic composition may be in the form of a powder, an aqueous solution, a hydroalcoholic solution or a water-in-oil emulsion.
    [0008] Presentation of Figures Figure 1 shows the percentage of recolonization by keratinocytes in the so-called "scratch test" test (see Example 2) after incubation of adipocytes with swertiamarine (SWT) and conditioning keratinocyte medium with the adipocyte medium, with TGF-13 (reference product) or in the presence of dilution solvent only (Control DMSO). Figure 2 shows the effect of swertiamarine and TGF-13 on fibronectin synthesis by normal dermal fibroblasts compared to the control experiment (see Example 3). Figure 3 shows sections of skin explant with or without adipose tissue after incubation for 9 days with or without treatment with swertiamarine. DESCRIPTION OF THE INVENTION Swertiamarin (CAS RN: 17388-39-5) belongs to the family of iridoids and has the following formula: It is a natural compound that can be isolated from certain species belonging to the family Gentianaceae such as species of the genus Swertia, Gentiana or Centaurium. For example, swertiamarine can be isolated from plants such as Swertia Chirata or Swertia milensis. Alternatively, swertiamarine can be obtained by chemical synthesis. Swertiamarine is marketed in purified form (purity of at least 95%) or in the form of enriched extracts. Swertiamarine has been described in the scientific literature, among others, for its antidiabetic and anti-cholesterol properties.
    [0009] Surprisingly, the Applicant has shown that swertiamarine is capable of stimulating the proliferation of keratinocytes. In particular, the Applicant has demonstrated that swertiamarine induces the production of keratinocyte growth factor (KGF) by adipocyte cells (Example 1). The Applicant has also shown on the basis of a "Scratch assay" type test that it is possible to induce proliferation of keratinocytes by incubating them in the presence of a culture of adipocytes pretreated with swertiamarine (Example 2). ). Swertiamarine was also able to promote the growth of human skin explants and increase the thickness of the epidermis (Example 3). Finally, the Applicant has shown that swertiamarine was able to directly stimulate the metabolism of the dermis, in particular to stimulate the production of fibronectin, a key glycoprotein of the extracellular matrix. By its ability to induce the proliferation of keratinocytes and / or the production of constitutive glycoproteins of the dermis, swertiamarine finds a direct application in cosmetics, in particular as an anti-wrinkle or anti-aging agent for preventing or treating the signs of skin aging. More generally, swertiamarine can be used as a cosmetic agent to treat or prevent non-pathological damage to the skin requiring restoration or regeneration of the epidermal tissue. For example, swertiamarine can be used as an anti-redness agent. Swertiamarine also has applications in the therapeutic field, in particular as a healing agent or as a regenerative agent for the epidermis, for example in the treatment or prevention of skin or mucous membrane lesions. Uses of Swertiamarin According to the Invention In the context of the present, swertiamarine can be used in the form of an isolated product or in the form of a plant extract enriched with swertiamarine. The plant extract enriched with swertiamarine can be obtained from a plant belonging to the family Gentianaceae, such as species of the genus Swertia, Gentiana or Centaurium. Preferably, the plant extract enriched with swertiamarine is obtained from a plant or part of a plant (leaf, flower, stem and / or seed) belonging to the genus Swertia such as Swertia Chirata or Swertia milensis. The term "an extract enriched in swertiamarine" an extract comprising at least 90% by weight of swertiamarine. In some embodiments, swertiamarine is used in the form of a plant extract of Swertia comprising at least 90% by weight of swertiamarine. In some embodiments, it is an extract of Swertia Chirata or Swertia milensis. A plant extract comprising at least 90% by weight of swertiamarine includes a plant extract comprising (or having a content) of at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% 99% or even 99.5% by weight of swertiamarine, said percentage relating to the total weight of the extract. The preparation of such extracts is described in the state of the art. Several extracts adapted to the implementation of the present invention are commercially available. These extracts can be obtained from any part of a plant known to contain swertiamarine, such as seeds, leaves, roots, stems or flowers.
    [0010] According to a first aspect, the subject of the present invention is the uses, preferably cosmetic and non-therapeutic, of swertiamarine. Swertiamarine can be used, preferably for cosmetic purposes, to stimulate the formation or regeneration of the epidermis, in particular to stimulate the proliferation of keratinocytes. Swertiamarine can also be used to stimulate the production of a skin protein. The term "skin protein" is understood to mean any constituent protein of the extracellular matrix, in particular collagen and fibronectin. According to an additional aspect, swertiamarine can be used for cosmetic purposes to stimulate the metabolism of the dermis, in particular to stimulate the production of fibronectin in the dermis. The present invention also relates to the cosmetic use of swertiamarine to promote regeneration and / or restoration of the dermis and / or epidermis, or to control or prevent non-pathological atrophy of the epidermis.
    [0011] In particular, swertiamarine can be used to prevent or treat non-pathological damage to the skin. "Non-pathological alteration of the skin" means any non-pathological change in the visual appearance or mechanical properties of the skin. Non-pathological alterations of the skin may result, especially skin aging, fragility or sensitivity of the skin (so-called reactive skin) or exposure of the skin to certain external conditions. In some embodiments, swertiamarine can therefore be used as an anti-aging or anti-wrinkle cosmetic agent.
    [0012] For the purposes of the invention, the term "skin" refers to any part of the skin of the human body, in particular the skin of the face, including the lips and eyelids, the neck, the skin of the hands and the skin of the feet. For the purposes of the invention, the term "signs of skin aging" is understood to mean any alteration or modification of the visual appearance or the mechanical properties of the skin, in particular of the non-pathological epidermis resulting from skin aging, which it is chronological (chrono-aging) and / or photo-induced (photo-aging). Thus, the signs of aging include, but are not limited to, thinning of the skin, particularly of the epidermis, the appearance of a microrelief, the appearance of fine lines and / or wrinkles on the skin, including in the lips and eyelids, wilting or sagging of the skin, loss of radiance of the skin, blurred complexion, dark circles in the eyes, loss of skin density, loss of firmness of the skin skin, loss of skin tone, loss of elasticity of the skin, alteration of the smooth appearance of the skin, and / or increased roughness of the skin. By way of examples, by virtue of its properties on the proliferation of keratinocytes and / or on the metabolism of the dermis, swertiamarine can be used in the cosmetic context to: stimulate the metabolism of the epidermis and / or the regeneration of the skin epidermis, in particular for combating aging of the skin, more specifically of the epidermis; To improve the radiance of the complexion or to unify the complexion; to reduce dark spots, to prevent, attenuate or treat dark circles, to rejuvenate aging skin, to prevent, attenuate or treat wrinkles, and / or fine lines, especially in mature skin; smooth the skin, or limit its roughness; correct age-related skin refinement; to prevent or treat dryness of the skin, preferably by increasing the barrier effect of the epidermis, to maintain or improve the mechanical characteristics of the skin, such as the tone, firmness, suppleness and / or elasticity of the skin, skin, and / or Smooth and / or restructure the lips, and / or to make them softer, less rough with a better defined outline.
    [0013] In the context of the present invention, the term "prevent a sign of skin aging", preventing, slowing down or delaying the appearance of the sign of skin aging. The term "treat a sign of skin aging" means correcting, attenuating, blurring, making less visible, reducing the appearance or even removing the sign of skin aging. In certain embodiments, swertiamarine is used cosmetically to prevent or treat a sign of skin aging, preferably chosen from a thinning of the epidermis, the appearance of a microrelief, the appearance of fine lines and / or wrinkles on the skin, including lips and eyelids, loss of radiance of the skin and alteration of a mechanical property of the skin such as loss of density, firmness, flexibility and / or or elasticity. The term "smoothing the skin" means attenuating and / or correcting the relief of the skin, including the lips, said relief being in the form of wrinkles, fine lines and / or stretch marks, and may even be following the presence of varicose veins; Swertiamarine can also be used, for cosmetic purposes, to prevent or treat other types of non-pathological alterations of the skin involving a non-pathological dysfunction of the renewal of the epidermis. This may be, for example, stretch marks or redness. Stretch marks can be formed during menopause, pregnancy or during a loss or significant weight gain. For example, swertiamarine can be used as an anti-stretch mark agent, for example to reduce the appearance of stretch marks. Swertiamarine can also be used to make varicose veins less visible. With skin aging and exposure to external conditions, the epidermis can thin and no longer play its role as a barrier. The skin becomes more sensitive and prone to redness and dry skin. In addition, thinning of the skin can make the subcutaneous micro-vessels more visible, which can increase the intensity of redness.
    [0014] Thus, by its ability to induce the proliferation of keratinocytes, swertiamarine can also be used, preferably for cosmetic and non-therapeutic purposes, as an anti-redness agent. Within the meaning of the invention, an "anti-redness agent" includes: an agent capable of preventing, treating or reducing redness, an agent capable of reducing the tendency to blush of a skin such as a reactive skin, fragile or sensitive, in particular in response to an external factor, or an agent capable of attenuating the red appearance associated with micro-vessels surface or an abnormality of the subcutaneous vascular system or make less visible said abnormality. For the purposes of the invention, the term "redness" includes redness and skin heat, particularly in the face for example in the cheeks, nose and chin. It may be episodic, transient or passenger-induced rash or heat (also called "flush") which may be induced or favored by an external factor, in particular by a climatic condition such as UV exposure, wind , an ambient temperature that is too low or too high, or a sudden change in temperature, by eating a food, such as a hot drink, alcohol or spices, or by stress or emotion. It may also be installed or permanent redness, for example associated with the presence of surface micro-vessels, angioma or telangiectosia. Finally, it may be transient or permanent redness associated with rosacea or erythrosis. For the purposes of the invention, "an abnormality of the subcutaneous vascular system" includes, among others, telangiectasia and angioma. In certain embodiments, swertiamarine is used to treat or prevent the appearance of transient or permanent redness in a type of skin selected from sensitive skin, fragile skin, reactive skin, intolerant skin, skin with a tendency to cut the skin. , skin with an erythrosic tendency or skin with an erythrocouperotic tendency Erythrosic or couperosic skin is defined as skin that may be affected by rosacea or erythrosis. Due to its general action on redness, stains and dark circles, swertiamarine can also be used as a complexing agent. Swertiamarine can also be used to make a varicose vein, surface micro-vessel, angioma or telangiectosia less visible on the surface of the skin. Surface micro-vessels can be congenital, or appear consecutively to skin aging or the development of rosacea. This action of swertiamarine is also based on its ability to stimulate the dermis and epidermis.
    [0015] In the cosmetic uses according to the invention, swertiamarine is present, as active agent, in a composition, preferably a cosmetic one. The swertiamarine may be incorporated into the composition in a purified form or in the form of a plant extract enriched in swertiamarine as defined above. In certain embodiments, swertiamarine is present in the form of a plant extract comprising at least 90% by weight of swertiamarine, said plant extract being preferably an extract of Swerta chirata or Swerta milensis. This composition is preferably intended to be administered topically. Typically, the composition is intended to be applied to the skin, for example on the skin of the hands or face, including the lips or eyelids.
    [0016] Swertiamarine (or plant extract enriched with swertiamarine) is generally present in the composition in an amount ranging from 0.0001% to 10%, preferably from 0.001% to 5% by weight, more preferably between 0.001%. and 0.5% or even 0.005% to 0.1%, the percentages being expressed relative to the total weight of the cosmetic composition.
    [0017] The composition may further comprise one or more additional active ingredients. Preferably, the additional active ingredient (s) exert a cosmetic effect. The term "active ingredient with a cosmetic effect, active agent with a cosmetic effect, or active with a cosmetic effect" means a compound capable of exerting at least one cosmetic effect on the skin or its appendages. "Cosmetic effect" means any non-therapeutic effect intended to modify and / or improve the appearance of the skin or mucous membranes such as the lips, to protect them from external aggressions (sun, wind, humidity, drought, chemicals) , or to prevent and / or correct the phenomena related to their aging. Thus, in some embodiments, swertiamarine may be present in a composition which further comprises an active ingredient with additional cosmetic effect. This active ingredient with a cosmetic effect may be chosen from the group consisting of vitamins, filters and sunscreens, anti-aging or anti-wrinkle agents, anti-sweat agents, antioxidants, lifting agents, firming agents and moisturizing agents. , soothing agents, exfoliating or exfoliating agents, mattifying agents, sebo-regulating agents, lightening active agents, anti-stain active agents, slimming agents, draining agents, self-tanning active agents, tanning accelerators and their combinations . In particular, the cosmetic composition may comprise tocopherols, and / or plant extracts such as extracts of linseeds, extracts of Vibrio exopolysaccharides, peptides such as trifluoroacetyl tripeptide-2.
    [0018] Preferably, the cosmetic composition may comprise an active agent chosen from an anti-wrinkle agent, an anti-aging agent, an anti-redness agent, an antioxidant, a moisturizing active agent, a soothing agent, a sebum regulating agent, a stain-repellent agent and their combinations. Even more preferably, the additional cosmetic effect active agent is chosen from an anti-wrinkle agent, an anti-aging agent, an antioxidant, a moisturizing agent, a lifting agent, a firming agent and combinations thereof. The additional active ingredient (s) with a cosmetic effect are typically present in an amount of from 0.0001% to 10% by weight of the composition. By way of example of moisturizing agents, mention may be made of urea, pidolic acid (PCA) and its derivatives, in particular its salts such as arginine PCA, chitosan PCA, and its copper salts (PCA copper). , magnesium (PCA magnesium), sodium (PCA sodium) or zinc, ethylhexyl PCA, calcium gluconate, hyaluronic acid and its salts and other glycosaminoglycans, frucose, glucose, isomaltose, lactose, trehalose, polydextrose, sucrose (sucrose), maltitol, mannitol, sorbitol, xylitol and other carbohydrates and derivatives, polyethylene glycols such as PEG-7, PEG-8, PEG- 10, PEG-12 or PEG-14, glycerine, propylene glycol, butylene glycol, betaine, citrulline, collagen and its derivatives, histidine, hydrolysates of silk, keratin or soy, extracts of plants rich in polysaccharides and / or polyphenols, for example extracts of Aloe, blueberry (Centaurea cyanus), and combinations of them. By way of example of anti-aging, anti-wrinkle or lifting agents, mention may be made of ascorbic acid and its derivatives, such as magnesium ascorbyl phosphate, glycosaminoglycans and their derivatives, ribose, sorbitol, and Cyathea polysaccharides. , collagen, flaxseed extracts (Linum usitatissimum), peptides such as Caprooyl-Tetrapeptide-3 and trifluoroacetyl tripeptide-2, extracts of Polygonum aviculare, extracts of brown algae, in particular Ascophyllum nodosum fern extracts, in particular Cyathea Cumingii. Examples of soothing agents that may be mentioned are allantoin, extracts of aloe, birch (for example Betula alba) and willowherb (Epilobium angustifolium). , chestnut (eg Castenea sativa), blueberry (eg Centaurea cyanus), centella (eg Centella asiatica), horsetail (eg Equisetum arvense), fennel (eg Foeniculum vulgare), witch hazel ( for example Hamamelis vir giniana), ivy (eg Hedera helix), habiscus sabdariffa, lily (eg Lilium candidum), mauve (eg Malva sylvestris), lemon balm (eg Melissa officinalis), skullcap (eg Scutellaria). baicalensis), mimosa (for example Mimosa tenuiflora), potentilla (eg Potentilla erecta), oligosaccharide extract or oligosaccharide, for example linseed, peptides such as palmitoyl tripeptide-8, polysaccharides obtained by biotechnology as Alteromonas ferment extract and combinations thereof. As examples of antioxidants, mention may be made of HMR (hydroxy methyl resorcinol), ascorbic acid and its derivatives, vitamin B9, histidine hydrochloride, or an extract of fireweed (Epilobium augustifolium). The antioxidant and vitamin-active ingredients are generally used in a weight percentage of at least 1% relative to the total weight of the cosmetic composition. By way of example of sebo-regulating agents, mention may be made of flax lignans, rice powder, zinc gluconate, sarcosine, an extract of Cinnamomum zeylanicum bark, an avocado extract and the combinations thereof . As anti-redness agents, mention may be made of saponins, flavonoids, ruscogenins, esculosides, and extracts containing them, for example extracts of Ruscus, as well as certain essential oils, for example lavender or rosemary.
    [0019] By way of example of antitask agents, mention may be made of extracts such as licorice (Glycyrrhyza glabra), jackfruit extract (Artocarpus heterophyllus), Rumex extract (R.occidentalis), plant extracts belonging to citrus-like, plant extracts rich in stibenes such as resveratrol, petids such as oligopeptide-68, nonapetide-1, arbutin, kojic acid, magnesium ascorbyl phosphate and combinations thereof. The invention also relates to a cosmetic process for treating, attenuating or preventing a sign of skin aging, redness or cutaneous heating in an individual, said method comprising the administration of a cosmetically effective amount of swertiamarine, preferably by topical route. Another object according to the invention is a cosmetic process for smoothing the skin in an individual, for example to correct or attenuate wrinkles, fine lines or stretch marks, said method comprising the administration of a cosmetically effective amount of swertiamarine, preferably topically.
    [0020] Another object according to the invention is a cosmetic process for rendering a varicose, micro-surface vessel, angioma or telangiectosia in an individual less visible, or improving the appearance, said method comprising the administration of a cosmetically effective amount of swertiamarine, preferably topically, on the cutaneous area where varicose vein, surface micro-vessels, angioma or telangiectosia is visible. As specifically indicated, swertiamarine is typically administered in the form of a composition, said composition being preferably cosmetic and applied to the skin, for example in the face or hands. According to a further aspect, the present invention relates to the use of swertiamarine in the field of healing of lesions of the skin or mucous membranes. Thus, swertiamarine can be used to promote healing, in particular to promote epidermal regeneration, epidermal reconstruction and / or promote re-epithelization of the skin or mucosa affected by injury. This is preferably a therapeutic use of swertiamarine. More generally, swertiamarine can be used to prevent or treat a lesion of the skin or mucous membranes. Swertiamarine can thus be used for therapeutic purposes as a healing agent or as a re-epithelizing or regenerating agent for the epidermis. As mentioned above, swertiamarine can be used in the form of an isolated product or in the form of a plant extract enriched with swertiamarine, preferably obtained from a plant belonging to the genus Swertia such as Swertia Chirata or Swertia milensis. The lesion may be trauma to the skin or mucous membrane, for example, a cut, a scratch, a burn, including a chemical, thermal or contact burn, irritation, erythema, or a blister or blister. a lightbulb. The lesion may also result from exposure of the skin or mucosa to climatic aggressions such as wind or large temperature variations, to certain chemical products such as detergents, to certain therapeutic agents such as agents. anti-cancer, anti-acne, radiotherapy, laser or some cosmetic processes such as peeling or dermo-abrasion. The lesion can also result from a pathology, in particular a dermatosis such as pruritus, eczema, atopic dermatitis.
    [0021] Skin or mucosal injury may be surface cracks or deeper cracks such as cracks or crevices. In a preferred embodiment, swertiamarine may be used to treat a lesion of the skin or mucosa such as a cut, a burn, an irritation, a blister, a blister, cracks, micro-wounds, a crack, a crevice, or cracks. For example, it may be cracks or cracks in the lips or hands or cracking or cracks in the heels. For the implementation of the therapeutic uses according to the invention, swertiamarine (or plant extract enriched in swertiamarine) can be incorporated in any type of composition, whether cosmetic or pharmaceutical. As in the case of cosmetic uses, the composition is preferably intended to be administered topically, for example to be applied to the skin or the mucosa to be treated. The swertiamarine is generally present in the composition in an amount ranging from 0.0001% to 10%, preferably from 0.001% to 5% by weight, more preferably between 0.001% and 0.5% or even 0.005 %% 0.1%, the percentages being expressed relative to the total weight of the cosmetic composition. The composition may further comprise one or more additional active ingredients chosen from active agents with a cosmetic effect and / or from active ingredients with a therapeutic effect. By way of example, the additional active principle may be chosen from the group consisting of soothing agents, moisturizing agents, anti-inflammatory agents, antioxidant agents, healing agents, agents promoting the regeneration of the epidermis, disinfectants, antimicrobial agents eg antifungals, disinfectants or antibiotic agents and combinations thereof. Typically, the soothing agents, the moisturizing agents and the antioxidant agents previously listed for the cosmetic uses according to the invention may also be used in the context of uses in the field of cicatrization according to the invention.
    [0022] Examples of agents promoting the regeneration of the epidermis include madecassol, oxaceprol, an extract of Calendula officinalis, an extract of St. John's Wort (Hypericum perforatum), an extract of Achilea (Achilea millefolium) , an extract of Ledum palustre, zinc oxide, balsam balm, vitamin A (retinol), dexpanthenol.
    [0023] By way of example of anti-inflammatory agents, mention may be made of corticosteroids, salicylic acid, and non-steroidal anti-inflammatory agents. As disinfecting agents, mention may be made of chlorhexidine and quaternary ammoniums; triclocarban, anionic derivatives, organo-mercurials, copper and / or zinc salts, para-hydroxybenzoic acid derivatives, hexamidine and its derivatives, iodinated derivatives. As antibiotic agents, there may be mentioned macrolides, fusidic acid, aminoglycosides, rifamycin, sulfonamides. As antifungal agents, there may be mentioned imidazole and its derivatives, terbinofine, selenium sulfide or the additional active ingredients are typically present in an amount of from 0.0001% to 10% by weight of the composition. According to another aspect, the subject of the present invention is the use of swertiamarine in combination with an active agent preferably chosen from soothing agents, moisturizing agents, anti-inflammatory agents, antioxidant agents, cicatrizing agents, antimicrobial agents, including antifungal agents, disinfectants or antibiotic agents, in the treatment or prevention of skin or mucosal injury or to promote healing. Swertiamarine and the additional active agent can be administered simultaneously, sequentially or separately over time. According to a further aspect, the present invention relates to a method for treating or preventing damage to the skin or mucosa in a patient, said method comprising administering to said patient an effective amount of swertiamarine, preferably topically. According to another aspect, an additional object according to the invention is the use of swertiamarine for the preparation of a composition, preferably a cosmetic or a pharmaceutical composition, intended for the treatment or prevention of a skin lesion or a mucous membrane. In the methods and uses according to the invention, the dose to be administered and the frequency of administration of swertiamarine vary according to the cosmetic effect or the desired therapeutic effect, the characteristics of the individual, in particular of his sex. , its age and skin type. For therapeutic uses according to the invention, the dosage may vary according to the sign or signs of aging that one wishes to prevent or treat. For cosmetic uses according to the invention, the dosage may vary according to the type and severity of the lesion that it is desired to treat. Typically, in the context of a cosmetic use according to the invention, the swertiamarine can be applied, on the area to be treated, once or twice a day, typically in the morning and / or evening, for several consecutive weeks or even several months. for example at least for 3 months.
    [0024] In the context of a therapeutic use according to the invention, swertiamarine can be applied to the wound to be treated two to three times a day, preferably until complete healing, for example for a week. The compositions adapted for carrying out cosmetic and therapeutic uses and processes according to the invention are detailed below. Compounds Containing the Swertiamarin According to the Invention The compositions adapted for the implementation of cosmetic or therapeutic uses and processes according to the invention generally comprise from 0.0001% to 10% of swertiamarine and from 80% to 99.9999% one or more pharmaceutically or cosmetically acceptable excipients. As mentioned above, swertiamarine can be introduced into said composition in purified or isolated form or in the form of a plant extract enriched with swertiamarine.
    [0025] The pharmaceutically or cosmetically acceptable excipient or excipients may be chosen from diluent agents, dispersing agents, gelling agents, emollients, targeting agents such as polycationic polymers or phospholipids, gums, resins, and solvents. in particular lower alcohols, in particular ethanol, isopropanol, dipropylene glycol, butylene glycol, propanediol, glycerol, sorbitol, and propylene glycol, fillers such as modified and polymerized starches, titanium dioxide , or a metal stearate, preservatives, essential oils, pearlescent agents, dyes, odor absorbers, pH-regulating agents or neutralizing agents, lubricating agents, thickeners, surfactants whose anionic, cationic, amphoteric or nonionic surfactants, humectants, wetting agents, dispersing agents, agents flavoring or perfuming, organic or inorganic pigments such as iron oxides, oily agents such as oils or fats of vegetable origin, fats of animal origin, synthetic oils such as petroleum jelly, silicone oils ( cyclomethicone), esters of fatty alcohol (cetyl alcohol), fluorinated oils, waxes, modified clays, bentones, metal salts of fatty acids, hydrophobized silica, polyethylenes, mica, the agents preservatives, antimicrobial agents, vehicles such as mineral, thermal or floral water, and / or other substances commonly used in formulation in the cosmetic or pharmaceutical field. In some embodiments, the swertiamarine is formulated using a vectorization system. The term "vectorization system" means a supramolecular system whose purpose is to promote the penetration of swertiamarine through the skin, preferably through the epidermis or even the dermis. In a preferred embodiment, the swertiamarine is encapsulated in the vectorization system. The vectorization system can be chosen from the group consisting of micelles, liposomes, including unilamellar or multilamellar liposomes, niosomes, ethosomes, lamellar systems, nanosomes, lipid or polymeric vesicles, nanospheres, microparticles. or nano-particles of natural or non-natural polymers, hydrogels. Preferably, swertiamarine is encapsulated in a vectorization system chosen from liposomes and lamellar systems. Particular examples of liposomes and lamellar systems for carrying out the present invention are described, inter alia, in French Patent Applications Nos. 1358589 and 1262303 filed in the name of the Applicant. By way of example, the vectorization system may be a lamellar system of lipid bilayers in aqueous phase, said lamellar system comprising a mixture of phospholipid, fatty acid and fatty alcohol preferably having a phospholipid / acid mass ratio. fat "of 0.5 to 1.5 and a mass ratio" fatty alcohol / fatty acid "of 2 to 4. The fatty alcohol may be selected from the group consisting of caprylic alcohol (octan-1-ol), capric alcohol (decan-1-ol), lauryl alcohol (dodecan-1-ol), myristyl alcohol (tetradec an-1-ol), palmitic alcohol (hexadecan-1-ol) stearyl alcohol (octadecan-1-ol), behenyl alcohol (docosan-1-ol) and mixtures thereof.
    [0026] The fatty acid may be selected from the group consisting of caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid and mixtures thereof. The phospholipid may be selected from the group consisting of phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositol, lysophospholipids, their hydrogenated derivatives, and mixtures thereof. As a further example, the vectorization system may be a liposome comprising at least one phospholipid and at least one glycolipid preferably in a "phospholipid / glycolipid" mass ratio ranging from 0.5 to 30, preferably from 1 to 10 .
    [0027] Preferably, the glucidic unit of the glycolipid comprises an oligomer or a fructose polymer (fructan) such as an inulin or levan radical. The glycolipid is selected from stearoyl inulin, inulin lauryl carbamate, palmitoyl inulin, undecylenoyl inulin and mixtures thereof. The phospholipid may be as defined previously for the lamellar system.
    [0028] The composition according to the invention may be in any known form. Preferably, it is a composition having a form suitable for topical administration. It can be in the form of aqueous, hydroalcoholic, oil-in-water (O / W) or water-in-oil (W / O) or multiple (triple: W / O / W or W / O / H) solutions. ), nanoemulsions, in particular O / W nanoemulsions, the drop size of which is less than 100 nm, aqueous gels, or dispersions of a fatty phase in an aqueous phase using spherules, suspensions, preferably in aqueous or hydroalcoholic media or a powder. The composition according to the invention may be in the form of a lotion, a milk, a cream, an ointment, a gel, a mousse, a solution, a ointment. The composition may also be included in a more complex system, for example in a dressing, or patch, in a soaked tissue, or in the form of a mucoadhesive tablet or film. Preferably, the composition according to the invention is a pharmaceutical or cosmetic composition, preferably a cosmetic composition and even more preferably a dermocosmetic composition. Thus, the composition according to the invention can also be in the form of a cosmetic product of any type. It may be a cosmetic treatment or a makeup or personal hygiene product, for example a lotion, a milk, a serum, an aqueous or oily gel, an emulsion, a cream or a cream gel. , a care water, an ointment, a balm, a foundation, a spray, an eye shadow, a stick, a lipstick, a gloss, a mousse, a deodorant, a nourishing mask, a shower gel, and an exfoliating or exfoliating product. As an illustration and not limitation, swertiamarine may be present as a healing or regenerating agent of the epidermis in a repair cream for damaged hands or in a chapped lip balm. Swertiamarine may also be present as a anti-wrinkle or anti-aging agent in a day cream for mature or aged skin. As an additional example, swertiamarine may be present as an agent for smoothing and / or restructuring the lips in a lipstick, lip gloss or lip balm. Swertiamarine may also be present as an anti-redness agent in a moisturizer for intolerant or sensitive skin. Alternatively, the composition according to the invention may be in the form of a medicament intended to be applied to the skin or a mucous membrane, for example a gel or a cream. The cosmetic or pharmaceutical compositions according to the invention may be prepared according to conventional methods, which are well known to those skilled in the art. According to a further aspect, the subject of the invention is a composition intended to be incorporated into a cosmetic or pharmaceutical composition. This composition therefore corresponds to a "precursor" composition.
    [0029] Preferably, this composition for the preparation of a cosmetic or pharmaceutical composition comprises: from 0.1 to 20%, preferably from 0.5 to 10%, of swertiamarine, said swertiamarine being preferably integrated in the form of a enriched plant extract, from 50% to 99.9% of a vehicle, preferably selected from a filler, an aqueous solvent, an organic solvent, preferably a lower alcohol such as ethanol, propanediol, butylene glycol, glycerin or isopropanol, a lipophilic agent and mixtures thereof, and optionally, from 0.1 to 30% of a pharmaceutically or cosmetically acceptable additional excipient, preferably selected from a targeting agent, a antioxidant, preservative, stabilizer, thickener, emulsifier, hydrophilic or lipophilic gelling agent, perfume, mineral or organic oil, and combinations thereof. the percentages being expressed by weight relative to the total weight of the cosmetic composition. As mentioned above, the plant extract is preferably an extract obtained from a species of Swertia and having a swertiamarine content of at least 90%, preferably at least 95%, by weight. As a filler, mention may be made of silica and its derivatives such as magnesium silicate, talc, a starch, a starch derivative such as maltodextrin and their mixture. Lipophilic agents that may be mentioned are fatty acids, fatty acid esters such as isopropyl palmitate, and / or fatty alcohols, preferably C 10 -C 30. As an emulsifying or vectorising agent, mention may be made of phospholipids such as phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositol, lysophospholipids, their hydrogenated derivatives, and mixtures thereof. The composition may comprise an aqueous or hydro-alcoholic phase obtained from mineral water, thermal water or floral water such as chamomile, mallow, cornflower or hamamelis water. Antioxidants include but are not limited to tocopherol and its derivatives, tocoquinone, HMR (hydroxy methyl resinol), polyphenols, isoflavones, propyl gallate, butylated hydroxy anisole (BHA), butylated hydroxy toluene (BHT) ) and their derivatives, histidine hydrochloride hydrochloride or an extract of Epilobium augustifolium. Examples of preservative compounds or antimicrobial agents are 2-bromo-2-nitropropane-1,3-diol, behentrimonium chloride, benzalkonium chloride, benzyl alcohol, butylparaben, cetrimonium chloride, derivatives of chlorhexidine (digluconate, dihydrochloride), chlorphenesin, climbazole, diazolidinyl urea, DMDM hydantoin, ethylparaben, hexamidine diisethionate, imidazolidinyl urea, iodopropynyl butylcarbamate , isobutylparaben, isopropylparaben, isothiazolinone, linalool, methyl benzoate, methylchloroisothiazolinone, methyldibromoglutaronitrile, methylisothiazolinone, methylparaben, o-cymen-5-ol, phenoxyethanol, piroctone olamine , polyaminopropyl biguanide, propylparaben, quaternium-15, sodium metabisulfite, sodium methylparaben, sodium propylparaben, stearalkonium chloride, triclosan, pyrith Zinc ione, caprylyl glycol, glyceryl caprate and caprylate, organic acids and their salts, preferably sodium or potassium, for example, sorbic acid and its salts, benzoic acid and its salts, salicylic acid and its salts, formic acid and its salts, dehydroacetic acid and its salts, levulinic acid and its salts, or anisic acid (methoxybenzoic acid) and its salts. The "precursor" composition according to the invention can be in various forms. It can be a solid composition, preferably in the form of a powder, in which the swertiamarine can be absorbed on a filler. Alternatively, the composition may be in the form of an aqueous solution, a hydroalcoholic solution or an inverse emulsion (water-in-oil emulsion). The present invention also relates to the use of said "precursor" composition for the preparation of a cosmetic or pharmaceutical composition. It goes without saying that said final cosmetic or pharmaceutical composition is particularly suitable for the implementation of any of the therapeutic or cosmetic uses according to the invention, and may have any of the characteristics described above in the part entitled "Compositions containing swertiamarine according to the invention".
    [0030] The "precursor" composition may be present in the final cosmetic or pharmaceutical composition in an amount of from 0.001% to 50%, preferably from 0.01% to 10% by weight relative to the total weight of the final cosmetic or pharmaceutical composition. Typically, the cosmetic or pharmaceutical composition can be obtained by mixing a "precursor" composition according to the invention with one or more excipients or vehicles that are acceptable from the pharmaceutical or cosmetic point of view. The invention also relates to in vitro uses of swertiamarine, in particular in the field of research or in the medical field. Swertiamarine can be used to promote the growth of skin explants in vitro. Skin explants can be used as a graft or autograft for the treatment of a skin lesion, or for research purposes, for example for the evaluation of active agents.
    [0031] The invention also relates to a method of in vitro culture of a skin explant comprising a step of treating the skin explant with swertiamarine. Swertiamarine can typically be added in a culture medium suitable for culturing or maintaining a skin explant or applied to the explant.
    [0032] Other aspects and advantages of the present invention will appear on reading the examples which follow, which should be considered as illustrative and in no way limiting.
    [0033] EXAMPLES EXAMPLE 1 Swertiamarin stimulates the production of keratinocyte growth factor (KGF) by adipocytes.
    [0034] The aim of this study was to quantify the keratinocyte growth factor (KGF) in the culture medium of human adipocytes cultured with and without swertiamarine. Protocol A 10 wt% stock solution of swertiamarine in DMSO was prepared. This solution was then diluted in the culture medium so as to obtain a final concentration of 0.0075% by weight of swertiamarine. A culture of normal human adipocytes, obtained from adipocytes taken by abdominoplasty in a 34-year-old woman, was incubated for 15 hours with the culture medium containing swertiamarine. As a negative control, an adipocyte culture incubated for 15 hours was used with a culture medium free of swertiamarine but containing the same amount of DMSO. At the end of the incubation, the amount of KGF was quantified in each culture medium by an ELISA test. The statistical significance of the differences between the "control" and "test" groups was assessed by one-way analysis (Anova) followed by the Holm AIDS test (p * <0.05).
    [0035] Results The statistical analysis of the results obtained for the different groups of experiments shows a significant increase in the amount of KGF in the culture media of the adipocytes incubated in the presence of swertiamarine compared to the control groups. An amount of 0.0075 wt% of swertiamarine induces an increase in the average amount of KGF in the culture medium of about 16.4%. EXAMPLE 2 Swertiamarine stimulates the proliferation of keratinocytes. ^ Model 1: Test called "scratch assay" The purpose of this study was to evaluate the effect of swertiamarine on a monolayer culture model of human keratinocytes. Protocol Normal keratinocytes surgically removed from a 45-year-old woman were cultured to obtain a monolayer culture of keratinocytes. When confluence was reached, a "scratch" was made in each cell culture so as to locally remove an equivalent amount of keratinocytes.
    [0036] Each keratinocyte culture was then incubated at 37 ° C. in a humid atmosphere and in the presence of 5% CO 2, in the presence of an adipocyte culture medium conditioned with swertiamarine (0.0025%, 0.005%, 0.0075%). % by weight), for 72 hours. Swertiamarine was introduced into the adipocyte culture medium by dilution of a 10% stock solution in DMSO. The final amount of DMSO in the culture media is 0.15%. As a control, a keratinocyte culture incubated under the same conditions was used in the presence of a culture medium comprising normal human adipocytes in suspension without swertiamarine but containing 0.15% of DMSO (DMSO control experiment). For validation purposes, a keratinocyte culture was incubated in the presence of TGF-13 growth factor (10 ng / ml) under the same conditions (TGF- (3) control.) The area corresponding to the "lesion" (c that is to say at the zone where the keratinocytes were removed) was measured before (t = 0) and after incubation for each cell culture from optical micrographs using Image J software.
    [0037] The results were expressed as percentage of surface recolonized with respect to the area observed at t = 0. The statistical significance of the differences between the "DMSO Control" and "TGF-13 Controls" groups was evaluated using the t-test (***: p <0.001). The statistical significance of the differences between the "DMSO Control" and the "SWT" test groups was analyzed by one-way analysis (Anova) followed by the Holm AIDS test (p * <0.05). Results The results obtained are illustrated in Figure 1 which shows the average percentage of recolonization obtained after incubation for each group of experiments. Notably, the reference product, TGF-β, significantly induced cell recolonization after 72 hours of stimulation (+ 124.1%, p <0.001). This result was expected and validated all the experiments.
    [0038] In addition, the adipocyte culture medium conditioned by swertiamarine significantly stimulated the proliferation of keratinocytes and recolonization. Swertiamarine therefore strongly induced the healing process compared to the "DMSO Control" experiments. This induction of healing effect is observable at all the concentrations tested, including 0.0025% of swertiamarine where there is an increase of + 64.6% in the surface recolonized by the keratinocytes compared to the "DMSO control" group. ". Swertiamarine therefore stimulates the proliferation of keratinocytes and thus the regeneration of the epidermis. ^ Model 2: Expiant de peau The purpose of this study was to evaluate the effect of swertiamarine on human skin explants with and without adipose tissue.
    [0039] Protocol Skin samples were surgically taken from a Caucasian woman during a tummy tuck. 21 skin explants 10 mm in diameter were prepared from these samples, of which 12 are explants of skin without adipose tissue (explant epidermis + dermis) and 9 are explants of whole skin (epidermis + dermis + hypodermis) . The explants are kept alive in a BEM medium at 37 ° C in the presence of a humid atmosphere at 5% CO2. The skin explants were divided into three groups: Group 1: a cream containing swertiamarine at a level of 0.025 % was applied on days 0, 1, 2, 3, 6 and 7 of the incubation, on the surface of the skin explants with a spatula (1 pl in the morning and 1 pl in the evening), Group 2: a placebo cream (swertiamarine-free) was applied on days 0, 1, 2, 3, 6 and 7 of the incubation, on the surface of the skin explants using a spatula (1 μl morning and 1 pl evening) (1 pl morning and 1 pl evening), Group 3: this control group was kept alive without treatment (without application of placebo cream or cream swertiamarine) On day 9, the skin explants are recovered, chemically fixed in a formalin solution for 24 hours, dehydrated, impregnated with paraffin and then infiltrated with resin according to the prot Oole SOP H-53. Fine sections are then made in each explant and observed by light microscopy after staining. Results Whole-skin explants treated with swertiamarine show, after 9 days, between 10 and 12 cell layers of epidermis versus only 4-5 for the same untreated skin explants, and 5-6 for those treated with the placebo. Swertiamarine therefore induced a significant thickening of the epidermis. In addition, skin explants treated with swertiamarine do not show any significant morphological alteration. Swertiamarine has also been able to induce thickening of the epidermis in skin implants without adipose tissue (6-7 cell layer thickness), which shows that swertiamarine also has a direct effect on keratinocytes. These results are illustrated in Figure 3. This experiment illustrates again the ability of swertiamarine to induce the regeneration of the epidermis and the proliferation of keratinocytes.
    [0040] EXAMPLE 3 Swertiamarin Stimulates Fibronectin Synthesis by Skin Fibroblasts Fibronectin is an adhesion protein that plays a central role in anchoring cells in the extracellular matrix. It is also involved in the modulation of cellular functions. Fibronectin is mainly located in the dermis and at the level of the junction between the dermis and the epidermis. This protein is sensitive to proteolytic cleavage, a phenomenon that is accentuated during aging and has the effect of affecting the integrity of the dermis by decreasing the amount of fibronectin and increasing the amount of denatured protein.
    [0041] The purpose of this study was to identify the effect of swertiamarine on fibronectin production by dermal fibroblasts. Protocol The test used was based on the synthesis of fibronectin induced by TGF-13 by normal dermal human fibroblast cells (NHDF) in monolayer culture. The culture was carried out using as culture medium DMEM (Eurobio, CMODME70-08) containing 10% fetal calf serum (Eurobio, CVFSV00-0U), 1% antibiotics (penicillin / streptomycin, Eurobio, CABPES01-0U) and 1% L-glutamine (Eurobio, CSTGLUOO-OR), at a temperature of 37 ° C under 5% CO2 and 95% moisture. The cells were then seeded, in the presence of complete DMEM, in microplates at a rate of 2.5 * 104 cells per well and then incubated at a temperature of 37 ° C. under 5% CO2 and 95% humidity. The culture medium was replaced after 24 hours to bring the cells to a state of quiescence.
    [0042] Then, the cells were incubated in the presence of TGF-13 or swertiamarine for 24 h or 48 h. The cell supernatants were then collected in order to quantify fibronectin by an ELISA test (BMS028, Ebiosciences). The cell viability rate was also determined by the standard MTT test. As a control, cells were incubated under the same conditions but in the absence of TGF-13 of swertiamarine (control). The results were expressed as a percentage of the amount of fibronectin produced per mL relative to the amount of fibronectin produced for the control experiment group. Results The results obtained are illustrated in Figure 2 which shows the average percentage of fibronectin produced in the experimental groups. The percentage is expressed in relation to the amount of fibronectin produced for the control experiment.
    [0043] It is observed that the reference product, namely TGF-β, significantly induced the production of fibronectin (+ 64%). This result was expected and validated all the experiments. Remarkably, swertiamarine induced very strongly the synthesis of fibronectin compared to control, and this at all concentrations tested. This effect is usually higher than that seen with TGF-P. By way of illustration, a concentration of 0.005% of swertiamarine induced an increase of more than 171% in the amount of fibronectin compared with the control experiments.
    [0044] Swertiamine is therefore also capable of restoring or improving the integrity of the dermis by inducing fibronectin synthesis. EXAMPLE 4 Examples of "Precursor" Compositions According to the Invention The following precursor compositions were prepared from an extract of Swertia Chirata having a content of at least 95% by weight of swertiamarine (hereinafter SWT extract). Composition A (in the form of powder): Compositions B and C (Compositions in hydroalcoholic solution form) Composition B (% by weight) SWT extract 1.25% Propanediol 70.00% Water 28.75% SWT 1 extract, 25% Silica 2.00% Maltodextrin 96.75% Composition A (% by weight) Composition C (% by weight) SWT extract 1.25% Glycerin 70.00% Water 28.75% ^ Composition D: Composition in the form of d EXAMPLE 5 Examples of Cosmetic Compositions According to the Invention As examples, the following cosmetic products can be prepared. These cosmetics incorporate one of the "precursor" compositions described above. ^ Oily Anti-Stretch Mark Gel Swertiamarine extract is present as a smoothing agent on the skin. This oily gel can be applied to the skin to be treated, particularly at the level of the breasts, the belly and the thighs, typically one to two times a day. * based on the total weight of the gel Phospholipids 15.8% Water 2.25% SWT extract 1.25% Composition D (% by weight) Isopropyl palmitate 80.7% A EmulmetikTM 950 1.00 Hydrogenated lecithin C Mirasil PTM Phenyl trimethicone 28.00% by weight * Glycerin Butylene Glycol Glycerin Butylene Glycol B Phospholipids (and) isopropylpalmitate (and) water (and) extract from Swertia Chirata D 2.00 Glycerin (and) water (and) extract from Nephelium seeds Longana E SveltessenceTM 1.00 Ingredient Phase INCI Name 49.00 19.00 Precursor Ingredient D ^ Lip Balm Swertiamarine extract is present as an epidermal regenerative agent for the treatment and prevention of chapped skin. The lip balm can be applied to the lips typically one to two times a day. * based on the total weight of the balm Phase Ingredient (INCI name)% by weight * Euphorbia wax Microcrystalline cellulose Ozokerite Copernicia wax cerifera Octyldodecanol Cocoglycerides Dicaprylyl carbonate Propylheptylcaprylate Polyglyceryl-2 triisostearate Precursor composition D (SWT extract) A 9 4.40 2 , 50 2.50 5.00 4.00 6.00 26.35 2.50 CI15850 Ci77891 Ci77499 Lecithin (and) polyglyceryl-3-palmitate Lecithin B 1.80 4.50 0.15 3.70 14.80 C Tocopherol (and) Helianthus annus seed oil Fragrance Water (and) glycerin (and) Linum usitatissimum seed extract Water D Propanediol Hydrogenated lecithin (and) C12-C16 alcohols (and) Palmitic acid Fragrance 0.50 0.50 1,30 1,00 1,00 0,80 0.20 - Anti-wrinkle day cream Swertiamarine extract is present as an anti-wrinkle agent, that is, as an agent to prevent or reduce wrinkles and / or fine lines. This cream is typically applied to the face, preferably in the morning, on clean skin and before makeup. * based on the total weight of the cream H 0.20 Fragrance Elegance 4042% by weight * Phase Ingredient Name INCI Deionized water FDC Red 4 Solution 0.1% water water (and) CI 14700 A 52.70 0.20 Silicate Magnesium and Aluminum Glycerin Hydroxyethylcellulose Chlorphenesin Sodium Phytate (and) Water Hydrogenated lecithin (and) C12-C16 alcohols (and) Palmitic acid B Veegum HS Glycerin Natrosol 250 M Pharm 0.50 5.00 0.30 C Chlorphenesin DermofeelTM PA -3 BiophilicTM H 0.30 0.10 4.00 Plant Oil Coco-Caprylate Butyrospermum Parkii Butter (Shea) Dimethicone Butylene Glycol Dicaprylate / Dicaprate Glyceryl Stearate Citrate Stearic Acid Tocopherol (and) Helianthus Seed Oil Annuus D Cegesoft PS 6 Cetiol C5 Lipex Shea Dc 200.5Cs DermofeelTM BGC DermofeelTM GSC Stearine DermofeelTM Toco 70 Non Gmo 3.00 3.00 5.00 3.00 7.00 1.00 1.00 0.20 Lanablue® Mamaku Vital Essence Nature PF SculptessenceTM Precursor composition C Sorbitol (and) Water (and) extracted from algae Water (and) Glycerin (and) leaf extract of Cyathea Medullaris Water (and) Glycerin (and) extracted from Linum usitatissimum seed Glycerin (and) water (and) extracted from Swertia Chirata E 1.00 2.00 5, 00 4.00 DermosoftTM 1388 SJ Touch 1 Fragrance Polymethyl Methacrylate F 3.00 G 2.00 ^ Anti-redness cream * based on the total weight of the cream Deionized water Water 66.1 Glycerin 4 Glycerine 0.5 Satiaxane xanthan range CX 91 Hazelnut oil Corylus oil Avellana Beeswax 4 Beeswax B 3 Shea Butter Butyrospermum Parkii (Shea) Butter 5 Water Deionized Water E Relax 2020/2 0.4 Fragrance% by weight * DermosoftTM GMCY Glyceryl Caprylate 0 Hydrogenated lecithin (and) C12-C16 alcohols (and) Palmitic acid BiophilicTM H 4 Sunflower oil Helianthus Annuus seed oil DermofeelTM Toco 70 Non Gmo Tocopherol (and) Helianthus seed oil Annuus 0.2 Maltodextrin (and) silica (and) extract of swertia chirata C 2 potassium sorbate pot sorbate Assium D 0.3 Phase Ingredient INCI Name Precursor Composition A
    权利要求:
    Claims (10)
    [0001]
    REVENDICATIONS1. Cosmetic use of swertiamarine or a plant extract enriched with swertiamarine as an agent stimulating the formation or regeneration of the epidermis and / or as an agent stimulating the metabolism of the dermis to prevent or treat non-pathological damage skin or to improve the appearance of the skin.
    [0002]
    2. The cosmetic use of swertiamarine or a swertiamarine-enriched plant extract according to claim 1, wherein said plant extract is an extract obtained from a species of Swertia, preferably Swertia ehirata or Swertia milensis, and which comprises at least 90% by weight of swertiamarine.
    [0003]
    3. Use of swertiamarine or a plant extract according to any one of claims 1 to 2, said swertiamarine or said plant extract being used as an anti-redness agent, anti-aging agent, agent anti-wrinkle, unifying agent of the complexion or agent for smoothing the skin.
    [0004]
    4. Use of swertiamarine or a plant extract according to claim 1 or 2, wherein said swertiamarine or said extract is present, as active agent, in a composition, preferably cosmetic, intended to be administered by topical.
    [0005]
    5. Use of swertiamarine or a plant extract according to claim 4, wherein the composition is intended to prevent, or treat a sign of skin aging, prevent, or treat stretch marks, and / or to make less visible micro-vessels of surface.
    [0006]
    6. Use of swertiamarine or a plant extract according to claim 5, wherein the sign of skin aging is selected from the group consisting of a thinning of the skin, in particular of the epidermis, the appearance of a microrelief, the appearance of fine lines and / or wrinkles on the skin, including lips and eyelids, wilting or sagging of the skin, loss of radiance of the skin, dark circles, a cloudy complexion , loss of skin density, loss of firmness of the skin, loss of skin tone, loss of elasticity of the skin, alteration of the smooth appearance of the skin, and / or increased the roughness of the skin.
    [0007]
    The use of swertiamarine or a plant extract according to claim 5, wherein the composition is for treating or preventing transient or permanent redness, preferably in a skin selected from the group consisting of sensitive skin, fragile skin, reactive skin, intolerant skin, skin with a tendency to have rosacea, skin with an erythrosic tendency and skin with an erythro-rosacea tendency.
    [0008]
    8. Use of swertiamarine or a plant extract according to any one of claims 4 to 7, wherein the swertiamarine is from 0.0001% to 10% by weight, preferably from 0.001% to 5% by weight, more preferably between 0.005% and 0.5% by weight of the total weight of said cosmetic composition.
    [0009]
    9. Use of swertiamarine or a plant extract according to any one of claims 4 to 8, the composition further comprising at least one additional cosmetic agent, preferably selected from the group consisting of vitamins, filters and sunscreens, anti-aging or anti-wrinkle agents, antioxidants, lifting agents, firming agents, anti-blemish agents, anti-redness agents, slimming agents, draining agents, moisturizing agents, soothing agents , exfoliating or exfoliating agents, tanning agents, sebo-regulating agents, lightening active agents, self-tanning agents, tanning accelerators and combinations thereof.
    [0010]
    10. Use of swertiamarine or a plant extract according to any one of claims 4 to 9, wherein the composition is selected from the group consisting of aqueous solutions, hydroalcoholic solutions, oil-in-water emulsions ( H / E) or water-in oil (W / O) or multiple (triple: W / H / E or H / E / H), the nanoemulsions, in particular nanoemulsions O / W, whose drop size is lower at 100 nm, aqueous gels, or dispersions of a fatty phase in an aqueous phase using spherules, suspensions, preferably in aqueous or hydroalcoholic media, liposome suspensions, powders, lotions, milks, creams, ointments, gels, mousses, and ointments. Use of swertiamarine or a plant extract according to any one of claims 4 to 10, wherein the composition is a cosmetic product, a product of makeup or a personal hygiene product, for example a lotion, a milk, a serum, an aqueous or oily gel, an emulsion, a cream, a cream-gel, a water of care, an ointment, a balm, a foundation, a spray, an eye shadow, a stick, a lipstick, a gloss, a lip balm, a mousse, a deodorant, a nourishing mask, a shower gel, and an exfoliating or exfoliating product 12. Swertiamarine or plant extract enriched with swertiamarine for use as a as a healing agent or as a regenerative agent of the epidermis, in the treatment or prevention of an injury to the skin or mucous membrane, in particular a cut, a burn, an irritation, an erythema, a blister , a blister, cracks, micro-wounds, a crack, a crevice, or cracks. 13. Swertiamarine or swertiamarine enriched plant extract for use according to claim 12, wherein the swertiamarine or said extract is intended to be administered topically and, optionally, in combination with another active ingredient, preferably selected from the group consisting of soothing agents, moisturizing agents, anti-inflammatory agents, antioxidants, healing agents, disinfectants, antimicrobial agents and combinations thereof. 14. A pharmaceutical or cosmetic composition for use in the treatment of a lesion of the skin or mucosa, said composition comprising swertiamarine or a plant extract enriched with swertiamarine as a healing agent or regenerative agent of the epidermis. 15. A pharmaceutical or cosmetic composition for use according to claim 14, comprising from 0.0001% to 10% by weight, preferably from 0.001% to 5% by weight, more preferably between 0.005% and 0.5% by weight. swertiamarine weight. 16. A pharmaceutical or cosmetic composition for use according to claim 14 or 15, said composition comprising an additional active ingredient preferably selected from the group consisting of soothing agents, moisturizing agents, anti-inflammatory agents, antioxidants, healing agents, disinfectants, antimicrobial agents and combinations thereof 17. Cosmetic or pharmaceutical composition according to one of claims 14 to 16; or swertiamarine-enriched plant extract according to claim 12 or 13, wherein said plant extract is an extract obtained from a species of Swertia, preferably Swertia chirata or Swertia milensis, and which comprises at least 90% by weight of swertiamarine. 18. Composition for the preparation of a pharmaceutical or cosmetic composition, comprising: from 0.1 to 20% of swertiamarine, said swertiamarine being preferably integrated in the form of a plant extract enriched with swertiamarine, in particular an extract obtained from from a species of Swertia such as Swertia chirata or Swertia milensis, from 50% to 99.9% of a vehicle, preferably selected from a filler, an aqueous solvent, an organic solvent, preferably a lower alcohol such as ethanol, propanediol, butylene glycol, glycerine or isopropanol, a lipophilic agent and mixtures thereof, and optionally 0.1 to 30% of a pharmaceutically acceptable additional excipient or cosmetic, preferably selected from a targeting agent, an antioxidant, a preservative, a stabilizing agent, a thickening agent, an emulsifier, a hydrophilic or lipophilic gelling agent, a perfume, a mineral oil ale or organic, and their combinations. 19. A composition according to claim 18, wherein said composition is in the form of a powder, an aqueous solution, a hydroalcoholic solution or an oil-in-oil emulsion.
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    同族专利:
    公开号 | 公开日
    US20170020796A1|2017-01-26|
    EP3116599B1|2020-12-23|
    EP3116599A1|2017-01-18|
    FR3018191B1|2018-01-12|
    ES2856480T3|2021-09-27|
    WO2015136198A1|2015-09-17|
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    法律状态:
    2016-02-23| PLFP| Fee payment|Year of fee payment: 3 |
    2017-02-22| PLFP| Fee payment|Year of fee payment: 4 |
    2018-03-26| PLFP| Fee payment|Year of fee payment: 5 |
    2020-03-25| PLFP| Fee payment|Year of fee payment: 7 |
    2021-03-25| PLFP| Fee payment|Year of fee payment: 8 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1451920A|FR3018191B1|2014-03-10|2014-03-10|COSMETIC USES OF SWERTIAMARIN|
    FR1451920|2014-03-10|FR1451920A| FR3018191B1|2014-03-10|2014-03-10|COSMETIC USES OF SWERTIAMARIN|
    PCT/FR2015/050569| WO2015136198A1|2014-03-10|2015-03-09|Cosmetic uses of swertiamarin|
    EP15714589.7A| EP3116599B1|2014-03-10|2015-03-09|Cosmeticuse ofswertia-marine|
    ES15714589T| ES2856480T3|2014-03-10|2015-03-09|Cosmetic uses of swertiamarin|
    US15/124,717| US20170020796A1|2014-03-10|2015-03-09|Cosmetic uses of swertiamarin|
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