FR3019041A1 - COMPOSITION CONTAINING AT LEAST ONE BLUEBERRY EXTRACT, METHODS OF OBTAINING SAME AND COSMETIC AND PHARMACEUTICAL USE THEREOF - Google Patents

Abstract

The invention relates to a method using cornflower seed as a raw material for obtaining, on the one hand, an oil and, on the other hand, an extract titrated with moschamin. The invention also relates to a cosmetic or pharmaceutical composition containing, as active agent, the extracted oil and / or a liquid fraction obtained by extracting the cake separated from the oil. The invention also relates to a use of these compositions for the treatment of diseases related to pigmentation disorders or inflammatory activities.

Description

The present invention relates to obtaining extracts of a plant that is widespread, particularly in Europe, and their uses in cosmetic compositions or in pharmaceutical compositions. More specifically, it relates to new applications of said plant for treating the skin. Said plant is a herbaceous herbaceous plant of the family Asteraceae, commonly called the blueberry which grows very often in cereal fields which it is often recognized as adventitious. The blueberry is scientifically named Centaurea cyanus L. The flowers are edible raw to decorate salads or desserts. In terms of traditional uses, the blueberry decoction was prescribed in case of irritation of the eyes and eyelids and to fight against conjunctivitis, and more generally for inflammations of the skin and mucous membranes. In cosmetology, blueberry flower water is used for its washing and cleansing properties. According to the article by N. Garbacki et al. (1999) (Journal of Ethnopharmacology, 68 (1-3), 235-241), the anti-inflammatory properties of blueberry flowers are confirmed by the presence of a polysaccharide. The article by S. D. Sarker et al. (2001) (Phytochemistry 57 (8), 1273-6) describes the presence of indoles in blueberry seeds. Another article by JB Park (2012), (Nat Prod Res 26 (16), 1465-72) demonstrates the effect of one of the indoles, moschamin, as a cyclooxygenase inhibitor and an inhibitor of forskolin-induced cAMP. Finally, the article by J.S. ROH et al. (2004) (Biol Pharm Bull 27 (12), 1976-1978) discloses an inhibitory effect on tyrosinase of moschamin and its derivatives, as well as an inhibitory effect of these same compounds on the synthesis of 2 Melanin by B16 melanocytes. According to this publication, these compounds would therefore have depigmenting properties. The present invention demonstrates novel cosmetic and pharmaceutical applications of the genus Centaurea, in particular cornflower, as a pro-pigmenting agent inducing melanin synthesis and an agent for improving aged skin or skin damaged by various dermatoses, such as psoriasis or atopic dermatitis. For example, it has been found that blueberry extracts significantly improve melanin synthesis and / or epidermal protection to combat external aggression and thus have a protective skin role. The subject of the present invention is a process for treating at least one herbaceous plant of the Asteraceae family, characterized in that the plant is subjected to an extraction phase making it possible to separate from the plant a liquid oil. at 20 ° C and a solid cake. According to a first aspect of the invention, the process defined above is characterized in that the treatment is carried out on a single plant designated by the name "Centaurea sp". According to another aspect of the invention, the plant subjected to the treatment is obtained by in vitro or in vivo culture. According to another aspect of the invention, the plant subjected to the treatment is constituted by seeds. According to another aspect of the invention, the extraction phase is chosen from the group formed by the solid-liquid extraction in an alcoholic, aqueous-alcoholic or aqueous medium or else in a solvent medium using ketone (s), ester (s), ether (s), polyol (s), chlorinated products or supercritical CO2. According to another aspect of the invention, the extraction phase is carried out by using microwaves or cold pressure. According to another aspect of the invention, the cake is subjected to hydroalcoholic extraction to obtain a liquid fraction containing moschamin. The present invention also relates to a cosmetic or pharmaceutical composition obtained by the process according to the invention, characterized in that it contains, as active agent, at least one oil obtained during the extraction phase of the process. According to another aspect of the invention, the composition obtained according to the method defined above contains, as active agent, at least one liquid fraction obtained by hydroalcoholic extraction of the cake. According to another aspect of the invention, the composition comprises a mixture of the oil obtained by the extraction phase and the liquid fraction obtained by the treatment of the cake. According to another aspect of the invention, the composition is in the form of cream, gel, lotion, milk, O / W emulsion and W / O, solution, ointment, body oil, shampoo, soap, protective lip stick, stick and pencil for makeup. According to another aspect of the invention, in the composition, the active agent (s) is (are) placed in encapsulation means selected from the group consisting of microspheres, liposomes, glycospheres, chylomicrons, macro-micro-, and nanoparticles, macro-, micro- and nanocapsules. According to another aspect of the invention, in the composition, the active agent (s) is (are) absorbed on powdery organic polymers, talcs, bentonite or other mineral supports in powder form. According to another aspect of the invention, in the composition, the active agent (s) is (are) in powder form and constitutes (s) from 0.01% to 5% by weight. weight relative to the total weight of the composition. According to another aspect of the invention, in the composition, the active agent (s) is (or are) in encapsulated form and constitutes (s) from 0.01% to 25% by weight. weight relative to the total weight of the composition. According to another aspect of the invention, the composition contains at least one adjuvant taken from the group consisting of antibacterial agents, perfumes, gelling and viscosity polymers, surfactants and emulsifiers, hydrosoluble active ingredients, plant extracts, tissue extracts, marine extracts and synthetic actives. The invention finally relates to the use of a composition according to the invention for preventing and / or treating dermatological diseases related to the pigmentation disorder or to seborrheic, acneic, inflammatory and immunological activities, to be restored or repaired. inducing the pigmentation of the skin or hair, preventing or treating pathologies and disorders resulting from natural or premature aging of the skin or hair, dermatoses, such as psoriasis and atopic dermatitis, inflammatory conditions of the systems skin or hair causing itching, irritation, chronic redness or functional disorders of capillary fragility. The invention therefore demonstrates the possibility of using blueberry seed as a raw material to extract the oil on the one hand and on the other hand to produce an extract titrated with moschamin from cake 5 (residue obtained after extraction of the oil). The oily extract has remarkable properties both on the healthy skin by improving its elastic properties, by reducing its dryness, or by improving its barrier function but also on the skin damaged by external physical aggressions (UV, cold .. .), chemical or biological (various dermatoses). The extract titrated in moschamine presents, for its part, unexpected propigmenting properties as well as favorable properties in the case of skins injured by external physical aggressions (UV ...), chemical or biological (various dermatoses). Indeed, we show here that the moschamine possesses unlike what is published, propigmenting effects. Other derivatives close to the moschamin (cis or trans feruloyl-serotonin) such as caffeoyl-serotonin, coumaroyl-serotonin, centcyamine and their cis and trans isomers also have more or less marked propigmenting activities. We can therefore use other titrated plants in these compounds and their isomers to develop propigmenting actives. The present invention aims precisely to offer new pharmaceutical, dermatological or cosmetic compositions capable of propigmenting healthy or sick skin (vitiligo) while ensuring a good maintenance of its homeostasis. Another aspect relates to the use of these novel compositions for treating irritated skin, lesions or sensitized by external aggression in general and dermatoses in particular. The invention particularly envisages as an active agent in the above compositions a blueberry extract. By extract or "plant extract" is meant a blueberry extract of the genus Centaurea sp. It is more particularly an extract of Centaurea sp cells or specifically an extract of cells of at least one plant of the genus Centaurea sp of the Asteraceae family. This cell material can be obtained by in vitro or in vivo culture. By in vitro culture is meant all of the techniques known to those skilled in the art that artificially allow the production of a plant or part of a plant. By in vivo culture is meant all the cultivation techniques which make it possible to obtain a plant or a part of a plant. Thus, the extract may be an organ extract (root, stem, leaf, bark), or even organ cells, of at least one plant of the genus Centaurea sp of the Asteraceae family, or an extract of 20 undifferentiated cells of at least one such plant. Thus, the subject of the present invention is a cosmetic use of a blueberry extract either to propigment the skin or to protect the skin from external physical, chemical or biological agents, and / or to improve and / or enhance the hydration of the skin. skin. It also relates to a cosmetic treatment method either for propigmenting the skin or for protecting the skin from external physical, chemical or biological agents, and / or for improving and / or reinforcing the hydration of the skin, said method comprising a step according to which at least one blueberry extract is applied to the skin. According to another aspect of the invention, it relates to pharmaceutical applications of a blueberry extract, as presented hereinafter. One of the objects of the invention is a pharmaceutical composition comprising a blueberry extract, for repigmenting the skin depigmented by a disease (vitiligo, etc.) or depigmented by certain therapies (radiotherapies, etc.). Another object is a pharmaceutical composition comprising a blueberry extract, for repairing skin damaged by external physical, chemical or biological agents. This condition may result from the action of a physical, chemical or biological external agent and / or a disorder or disease, such as psoriasis or atopic dermatosis. In the therapeutic aim of the invention, blueberry extract may be administered topically, it may also be administered orally. An extract of cornflower according to the invention can be obtained by any method of extraction or purification known to those skilled in the art. In particular, mention may be made of solid-liquid extraction processes in alcoholic (in particular methanolic, ethanolic) and aqueous media, as well as in media using solvents such as ketones, esters, ethers, polyols and solvents. chlorinated and mixtures of at least two of the aforementioned solvents, such as hydroalcoholic media. Alternative methods to solvents can also be envisaged as supercritical CO2, microwaves, cold pressure to obtain the oil ... These extracts can be used as such in liquid or powder form, not purified or purified . If the extract is powdered, its drying may be conducted by any technique well known to those skilled in the art. The extract can be spray dried, evaporated or lyophilized. The powder thus obtained may be encapsulated in liposomes or other carriers and carriers for a better homogeneity of the composition and a better diffusion of the active product especially on the skin. The extract is preferably obtained from blueberry seeds. The authors have observed that it is possible from blueberry seeds to make a first extract consisting of recovering the oil and, with the cake, to make a second hydro-alcoholic extract making it possible to obtain an extract titrated with moschamin. . The first extract is of interest for maintaining healthy skins or repairing damaged skin while the second extract makes it possible to repigment depigmented skin or to propigment normal skin. In addition, this second extract allows, like the first, to repair damaged skin. The blueberry extracts according to the invention may be combined in the compositions of the invention with one another or with other compounds that complement the effect or even synergize this effect. By way of example but in a nonlimiting manner, mention may be made of associations with mucopolysaccharides, vitamins, ceramides, antiradical substances, UV filters, other propigmenting or effective active agents in dermatoses. Even the restorative activity of the extracts according to the invention is particularly advantageous when they are combined with substances having a healing effect such as proteins, hyaluronic acid, amino acids, or with anti-inflammatory substances, age, after-sun or with active anti-acne, anti-dermatoses ... The protective activity of the extracts vis-à-vis free radicals and UV is also very interesting in the hair field, especially in the case of association with substances facilitating the good condition of the scalp and that of the hair, such as minerals, vitamins, ceramides, protein extracts, mucopolysaccharid es, flowers or fruit acids. Thus, the compositions of the invention are particularly suitable for topical application to prevent and / or treat many skin disorders. The invention therefore particularly relates to the use of dermo-cosmetic cornflower extract, as a repairing agent and / or protector of the skin and the hair system such as hair, especially to fight against pigmentation disorders or external aggressions related to pollution, sun, oxidative stress, aging and skin pathologies leading to dysfunction of the homeostasis of the epidermis or hair. Direct application of the compositions of the invention relates to the fight against UV-induced aging and cell death. The invention also relates to a use of these compositions as a tanning extender. For cosmetic use, the compositions of the invention may be in the form of creams, gels, lotions, milks, O / W emulsions and the like. E / H, solutions, ointments, sprays, body oils, hair lotions, shampoos, aftershave lotions, 25 soaps, lip sticks, makeup sticks and pencils. In the form of gel, they include suitable excipients such as cellulose esters or other gelling agents, such as the carboxylic polymer "carbopol®" and guar gum for example. These cosmetic compositions may also take the form of a lotion or solution in which the extracts and / or molecules are in encapsulated form, for example in microspheres. These microspheres may, for example, consist of fat, agar and water. The active agents can also be incorporated into liposome, glycosphere-type vectors in chylomicrons, macro-, micro-, nano-particles as well as macro-, micro- and nanocapsules and also be adsorbed on organic polymers. powdery, talcs, 5 bentonites and other mineral supports. These emulsions have good stability and can be stored for the time necessary for use at temperatures between 0 and 50 ° C without sedimentation of the constituents or phase separation. The cosmetic compositions according to the invention comprise, on the order of 0.01 to 5% by weight, preferably between 0.1 and 2.5% of active agents when they are in powder form and in the order of from 0.01 to 25%, preferably from 0.5 to 10% when in encapsulated form. For the preparation of these compositions, the blueberry extracts are mixed with the excipients generally used in cosmetics. The cosmetic compositions of the invention may also contain additives or adjuvants which are customary in cosmetology, for example antibacterial agents or perfumes, but also extraction and / or synthetic lipids, gelling and viscosity polymers and surfactants. and emulsifiers, hydro or liposoluble active principles, plant extracts, tissue extracts, marine extracts, synthetic actives. The cosmetic or dermocosmetic use of extracts includes all skin and body care products including sun protection and tanning products, anti-aging products, anti-seborrhoeic products and tonics, products that improve the skin. appearance of the skin including acne treatment, skin rash, scalp treatment and hair loss.

The cosmetic compositions of the present invention may also comprise other complementary active principles chosen for their action, for example for sun protection, anti-wrinkle effect, antiradical and antioxidant activity, anti-irritant activity. , cellular nutrition, cellular respiration, hydration and cellular regeneration, anti-seborrhoeic treatments, as well as other active ingredients having an action on cutaneous tonicity, protection of the hair. The cosmetic compositions of the present invention are preferably used daily by applying them one or more times daily. The cosmetic compositions of the present invention are very well tolerated, exhibit no phototoxicity and their application to the skin for prolonged periods of time does not imply any systemic effects. The invention also relates to the use of blueberry extracts for the preparation of dermocosmetic compositions having repigmenting, propigmenting, anti-inflammatory and dermoprotective activity. These compositions are useful for preventing and / or treating, in particular, dermatological diseases related to pigmentation disorders or to seborrheic, acneic, inflammatory and immunological activities.

These dermocosmetic compositions are in liquid, powder, paste or emulsion form, alone or in combination with other substances. For preparations of these dermocosmetic compositions, blueberry extracts are mixed with excipients. Accordingly, in general, the invention relates to the use of a blueberry extract, for the preparation of a pharmaceutical, dermatological or cosmetic composition intended to restore pigmentation or to induce this pigmentation of the skin or skin. hair.

The invention also relates to the use of a blueberry extract for the preparation of a pharmaceutical, dermatological or cosmetic composition intended to prevent and / or treat pathologies and disorders resulting from natural or premature aging. skin or hair. ^ dermatoses, such as psoriasis and atopic dermatitis. 5 ^ inflammatory conditions of the cutaneous or hair systems, inducing itching, irritation, chronic redness, irritation and persistent itching and functional disorders of capillary fragility. 10 ^ a problem of pigmentation of the skin or hair. A pharmaceutical composition according to the invention further comprises at least one active agent as defined above, a vector, or a pharmaceutically acceptable excipient. The present invention is now illustrated, without limitation, by the following Examples 1 to 5. Example 1 illustrates methods for preparing blueberry extracts according to the invention. Examples 2 to 5 below illustrate the properties of the compositions of the invention, which have been evaluated in different biological models.

Example 1: Obtaining blueberry extracts 200 g of cornflower seeds, previously dried, were ground and macerated for 24 hours in 1 L of hexane. During the entire maceration, the mixture was maintained under stirring at 20 ° C.

After maceration, the plant residue was separated from the extract by clarification and filtration. The extract was then dried by evaporation in vacuo. The resulting liquid is filtered to remove the waxes. 48 g of a clear yellow oil were obtained and constitute the Ex1MH1103 extract. An industrial alternative to this method is the use of supercritical CO2 or pressure (cold for example) to obtain the extract 1: an oily extract or an oil which after analysis has been found to be more than 60% titrated. linoleic acid. After evaporation of the residual hexane, the cake (seed residue of the previous extraction) is macerated for 24 hours in 1 L of a 60% (v / v) ethanol solution in water. . Throughout the maceration, the mixture was stirred at 20 ° C. After maceration, the plant residue was separated from the extract by clarification and filtration.

The extract was then concentrated by evaporation under vacuum and then spray-dried. 10 g of a light brown powder were obtained and constitute the Ex3MF1103 extract. Ex3MF1103 extract was analyzed by HPLC. It contains 13% (m / m) of moschamine. The hydro-alcoholic extraction can be done with variable ratios ranging from 10/90 to 90/10. The content of moschamin will, however, be affected. We favor the ratios 50/50 to 10/90 water / alcohol for good contents 30 in moschamine.

Example 2: Promising properties of a blueberry extract: Measurement of melanin synthesis in B16 melanocytes We have unexpectedly observed that blueberry extract titrated with moschamin acts as a propigmenting agent on the human melanocyte. B16, contrary to what is published in the scientific literature. The tests were carried out by the company Bioalternatives, 10 according to their standard protocol and are presented below. The extract titrated with moschamin corresponds to the reference EX3MF1103 soluble at 50 mg / ml in DMSO. The proposed effective dose is 100 μg / ml, ie 0.01%.

Table 1: Cytotoxicity on B16 melanocytes. ii9110011 EX391F1103 uni: peul Stock solution petapanie to 0 abbot OR DOMO 0.046 0.14 0.41 123 3.70 11.1 333 100 98 gl 96 vo 95 96 97 95 103 108 Viability (9) 102 105 101 105 100 104 102 99 112 112 96 99 103 102 97 101 97 100 103 107 Peten 100 100 102 97 101 99 98 108 109 am 2 2 t 2 2 1 3 1 Morphological observation X '-, - ,, ,, Table 2: Pro-pigmenting activity on melanocytes B16. (S3MF1169: positive reference) laltaamt Osais of trom Orne »ranwollmins Commis MM 2.03m100102 UMM ........ 911223133 = su% Me p% PRP pie MM iMMIM 4-P4 Per. (44. ePas 9440 29 ma 16.2 3.7 Witness 16.1 10.0 59 6.0 07 100 - 0 - 189 3.1 62.0 422 102101114 13 "11 M MI 402 412 06 M Il M 11 ... 514 414 220 92 00227.0 135 102 87 95 04 170 1 70 7 .... 202 7011 232 133 11311211110 112,221 213 402 11.1 MI as 043 b 113 10 - 218 11.7 233 123 MM «232 190 132 132 94 240 7 172 7 343 14.3 17.0 7.0 262977 17.4 WI 7.1 7.3 07 in 4 and - 172 74 193 9.0 MMM 002M 912 103 29 82 O4 MO 60 IO - 212 92 234 12.0 Honey 222 102 126 12.9 00 MI 1 130 9 - 21.7 11.3 9.: amaaaelauraima aiimerameaoeuras 7.1 9w14.903004191227 / 20932 as .: 70.03 In the non-cytotoxic concentration, the extract exhibits significant propigmenting properties and dose-dependent properties.

EXAMPLE 3 Properties on the barrier function of the epidermis The blueberry oil or the oily extract obtained according to Example 1 was applied to the skin of 30 to 50 year-old volunteers. The general feeling is an improvement of the state of drought of the skin as well as a softening side.

Example 4: Propigmentation properties of a blueberry extract: Measurement of the tyrosinase activity in the normal human melanocyte Tests on normal human melanocytes showed that the moschamine and the extract titrated with moschamin stimulated the synthesis of melanin and that the key enzyme activity of pigmentation, tyrosinase, was significantly increased.

Example 5: Application in dermatoses Various cellular tests have made it possible to demonstrate that the oil (oily extract) and more particularly the extract titrated with moschamin could have favorable effects on atopic dermatitis. The models involved are the action of the extracts according to IDENT171-725103/14, the invention on mast cell degranulation (histamine release test) as well as on the release of neurotransmitters such as substance P and CGRP in sensory neurons or in co-cultures of sensory neurons and keratinocytes.

Claims (7)

REVENDICATIONS1. Process for the treatment of at least one herbaceous plant of the Asteraceae family, characterized in that the plant is subjected to an extraction phase which makes it possible to separate from the plant a liquid oil at 20 ° C. and a cake solid. 2. Method according to claim 1, characterized in that the treatment is carried out on a single plant designated as "Centaurea sp". 3. Method according to one of claims 1 or 2, characterized in that the plant subjected to the treatment is obtained by in vitro culture or in vivo. 4. Method according to one of claims 1 or 2, characterized in that the plant subjected to the treatment consists of seeds. 5. Method according to one of claims 1 to 4, characterized in that the extraction phase is selected from the group formed by the solid-liquid extraction in alcoholic, aqueous or aqueous medium or in a solvent medium by means of of ketone (s), ester (s), ether (s), polyol (s), chlorinated products or supercritical CO2. 6. Method according to one of claims 1 to 4, characterized in that the extraction phase is performed by an implementation of microwaves or cold pressure. 7. Process according to claim 1, characterized in that the cake is subjected to a hydroalcoholic extraction to obtain a liquid fraction containing moschamin. Cosmetic or pharmaceutical composition obtained by the process of claim 1, characterized in that it contains, as active agent, at least one oil obtained during the extraction phase. 9. Cosmetic or pharmaceutical composition obtained according to the method of claim 7, characterized in that it contains, as active agent, at least one liquid fraction obtained by hydroalcoholic extraction of the cake. 10. Cosmetic or pharmaceutical composition obtained according to claim 7, characterized in that it comprises a mixture of the oil obtained in the extraction phase and the liquid fraction obtained by the treatment of the cake. 11. Composition according to one of claims 8 10, characterized in that it is in the form of cream, gel, lotion, milk, emulsion O / W and E / H, solution, ointment, body oil, shampoo, soap , lip stick, stick and pencil for makeup. 12. Composition according to one of claims 8 to 11, characterized in that its (or its) active agent (s) is (are) implemented in encapsulation means selected from the group consisting of microspheres, liposomes, glycospheres, chylomicrons, macro-micro-, and nanoparticles, macro-, micro- and nanocapsules. 13. Composition according to one of claims 8 11, characterized in that its (or its) active agent (s) is (are) absorbed (s) on powdery organic polymers, talcs, bentonite or other powdered mineral supports.14. Composition according to one of Claims 8 to 11, characterized in that its (or its) active agent (s) is (are) in powder form and constitutes (s) from 0.01% to 5% by weight. weight relative to the total weight of the composition. 15. Composition according to claim 12, characterized in that the active agent (s) is (or are) in encapsulated form and constitutes (s) from 0.01% to 25% by weight per relative to the total weight of the composition. 16. Composition according to one of claims 8 to 15, characterized in that it contains at least one adjuvant taken from the group consisting of antibacterial agents, perfumes, gelling and viscosity polymers, surfactants and emulsifiers, principles hydro- or liposoluble active ingredients, plant extracts, tissue extracts, marine extracts and synthetic actives. 17. Use of a composition according to one of claims 8 to 16 for preventing and / or treating dermatological diseases related to pigmentation disorder or to seborrheic, acne, inflammatory and immunological activities, to restore or to induce the disease. pigmentation of the skin or the hair, to prevent or treat pathologies and disorders resulting from the natural or premature aging of the skin or the hair, dermatoses, such as psoriasis and atopic dermatitis, inflammatory conditions of the cutaneous systems or hair causing itching, irritation, chronic redness or functional disorders of capillary fragility.