GARDENIA EXTRACT IN SKIN COLORING

Abstract

The present invention relates to the use of a cosmetic composition intended for colouring the skin, said cosmetic composition including, as an active principle, an aqueous extract of gardenia.

Description

Gardenia extract in skin coloring The present invention relates to the use of a Gardenia extract intended to color the skin. Human skin color, also called complexion, exhibits a continuous gradation from white to dark brown, almost black, sometimes with pinkish or coppery tones. Skin color is a striking individual characteristic, often considered an ethnic or socioeconomic marker. The quantity and nature of the pigments contained in the skin, as well as their distribution, are the main criteria determining its color. Genetics plays a crucial role in determining complexion, but so does sun exposure, as most humans tan under the influence of ultraviolet radiation. The absorption of certain medications, as well as certain medical conditions, can cause hyperpigmentation or depigmentation. Three pigments are responsible for skin color through their surface distribution. Carotene is a pigment whose color varies from yellow to orange.It accumulates in the stratum corneum and the adipose cells of the hypodermis and promotes melanin synthesis. It is present in certain plants, such as carrots. The second pigment is hemoglobin; when the skin is well-oxygenated, it gives fair skin its pinkish hue. Insufficient oxygenation gives it a bluish tint. Melanin is the most important pigment for skin color. The melanin level determines its color and provides varying degrees of protection against ultraviolet rays. The epidermis, hair, and body hair are colored by melanin, which is found in the deepest layer of the epidermis, the basal layer, and is produced by large cells called melanocytes. Melanin is synthesized in melanosomes from an amino acid, tyrosine. Tyrosinase is a key enzyme in melanin synthesis.The number and size of melanosomes determine the melanin content from one person's skin to another. Melanin absorbs ultraviolet and infrared radiation and captures free radicals, which are highly toxic and account for a large part of the sun's harmful effects. Self-tanner is a cosmetic product used to achieve a temporary tan similar to that obtained through sunbathing, but without sun exposure. It must be applied to the body to color the skin. Self-tanner contains dihydroxyacetone, a chemical agent that allows the skin to color. Therefore, there is significant demand for the development of new products that effectively color the skin and are easy to use, for example, through simple oral administration. Unexpectedly, the inventors found that an extract of Gardenia, taken orally and topically, could be useful for coloring the skin. Native to China and Japan, Gardenia jasminoides J. Ellis is an evergreen shrub in the Rubiaceae family, typically reaching 1 to 2 meters in height. This plant is cultivated in hot, humid tropical climates. The dark green leaves are opposite, elliptical to oval-oblong, 5 to 10 cm long and 2 to 7.5 cm wide, wedge-shaped at the base and acute or acuminate at the apex, with a short petiole and stipules fused in pairs. The white to ivory flowers are bell-shaped, 3 to 4 cm across, solitary, terminal, sessile, and highly fragrant. The fruit is a leathery, five-ribbed berry, 1 to 1.5 cm long, ovoid or ellipsoid, topped by the persistent calyx, yellow to red when ripe, and containing numerous seeds. The ripe fruit, harvested in autumn and dried, is listed in the Chinese pharmacopoeia. Traditional Chinese medicine prescribes gardenia fruit in various preparations: dried (Zhi-zi), fried (Chaozhi-zi), or charred (Jiaozhi-zi). Internally, it is prescribed as an antipyretic, for bacillary dysentery, pulmonary and urinary tract infections, hepatitis, or as a hemostatic agent for nosebleeds caused by fever. Externally, it is used to treat injuries, eye inflammation, bruises, wounds, and boils. In Japanese Kampo medicine, the fruit is used to treat pain, lung ailments, and jaundice. These traditional uses can be explained by the fruit's pharmacological properties: hemostatic, anti-inflammatory, stimulant, cholagogue, emetic, and diuretic. The other parts of the Gardenia jasminoides plant have numerous beneficial properties. The leaves, which are fever-reducing, are crushed in Malaysia to make poultices for treating migraines and lung inflammation. The bark, also a fever reducer and tonic, is used for fever, dysentery, and abdominal pain. In India, the root is used for dyspepsia and nervous disorders. The flowers, which are emollient, are useful for treating ophthalmia, gonorrhea, and vaginitis. The seeds are used externally as a paste to treat jaundice, rheumatism, and diverticulosis. In addition to these medicinal uses, the fruits are also used to color foodstuffs or textiles yellow to orange due to their richness in crocins, pigments identical to those of saffron. The main components of the fruit are: ^ iridoids, represented mainly by geniposide and gardenoside. The other iridoids present as well as the following compounds in smaller quantities: 6"-O-trans-sinapoylgenipin gentiobioside, 6"-O-trans-p-coumaroylgenipin gentiobioside, 6"-O-trans-cinnamoylgenipin gentiobioside, 6"-O-trans-p-coumaroylgeniposide, 6'-O-trans-p-coumaroylgeniposide, 10-O-succinoylgeniposide, 6'-O-acetylgeniposide, Gardenal-I, Gardenal-II, Gardenal-III, 6-β-hydroxygeniposide, 6-β-hydroxygeniposide, 6-β-methoxygeniposide, feretoside, genipin-β-gentiobioside, shanzhiside and lamalbidic and picrocrocinic acids. ^ carotenoids such as croceic acid, crocetin and crocins, glycosylated derivatives of crocetin.We distinguish between crocin 1 (crocetin gentiobioside), crocin 2 (crocetin gentiobioside glucoside) and crocin 3 (crocetin glucoside), ^ of the flavonoids: gardenin, quercetin, quercetin-3-rutinoside, quercetin-3-O-glucopyranoside, isoquercitrin, corymbosin, umuhengerin, nicotiflorin. > of caffeine-quinic derivatives (3-caffeoylquinic acid, 4-caffeoylquinic acid), 3,4-dicafeoylquinic acid, 3,5-dicafeoylquinic acid, 4,5-dicafeoylquinic acid, ethyl 5-O-caffeoylquinate, methyl 5-O-caffeoyl 3-O-sinapoylquinate, ethyl 5-O-caffeoyl 3-O-sinapoylquinate, methyl 5-O-caffeoyl 4-O-sinapoylquinate, ethyl 5-O-caffeoyl 4-O-sinapoylquinate, ethyl 3,5-di-O-caffeoyl-4-O-(3-hydroxy-3-methyl)glutarylquinate, methyl 3-O-caffeoyl-4-O- sinapoylquinic, methyl 3-O-cafeoyl-4-O-sinapoylquinate, methyl 3-O-cafeoyl-5-O-sinapoylquinate, 3,4-di-O-cafeoyl-5-O-(3-hydroxy-methyl)glutarylquinic acid, 3,5-di-O-cafeoyl-4-O-(3-hydroxymethyl)glutarylquinic acid. • phenolic acids such as chlorogenic, caffeic and 3,4-dihydroxybenzoic acids. ^ lignans: gardenianan A, syringaresinol, pinoresinol, syringaresinol-4-O-β-D-glucopyranoside, lariciresinol, alangilignoside D, lyoniresinol, lyoniresinol-9-O-D-glucopyranoside, balanophonin, glycosmic acid, ficusal and ceplignan. ^ sugars (mannitol). The present invention relates to the use of a cosmetic composition intended to color the skin, said cosmetic composition comprising, as an active ingredient, an aqueous extract of Gardenia. Preferably, the aqueous extract of Gardenia is derived from the species Gardenia jasminoides. According to one embodiment of the invention, the aqueous extract of Gardenia used to color the skin contains a mass fraction of crocins between 0.1 and 10%, preferably between 1 and 5%. The composition according to the invention can be formulated for administration to humans. The compositions according to the invention can be administered orally, sublingually, subcutaneously, intramuscularly, intravenously, transdermally, topically, or intranasally. Advantageously, the composition according to the present invention is intended for topical administration. Even more advantageously, the composition according to the present invention is intended for oral administration. In the latter case, the aqueous extract of Gardenia can be administered to humans in unit-dose forms, mixed with conventional pharmaceutical carriers. Suitable unit-dose forms include oral forms such as tablets, capsules, powders, granules, and oral solutions or suspensions; sublingual and buccal forms; subcutaneous or transdermal forms; and topical, intramuscular, intravenous, or intranasal forms. When preparing a solid composition in tablet form, the principal active ingredient is mixed with a pharmaceutical vehicle such as gelatin, starch, lactose, magnesium stearate, talc, acacia gum, silica, or similar substances. The tablets may be coated with sucrose or other suitable materials, or they may be treated to provide prolonged or delayed action and to release a predetermined amount of active ingredient continuously. A capsule preparation is obtained by mixing the active ingredient with a diluent and pouring the resulting mixture into soft or hard capsules. A preparation in the form of a syrup or elixir may contain the active ingredient together with a sweetener, an antiseptic, as well as a flavoring agent and an appropriate color. In a particular embodiment of the invention, the composition comprises, per unit dose, 10 mg to 1 g of Gardenia extract, preferably 20 mg to 500 mg, advantageously 50 mg to 250 mg and more preferably 100 mg to 200 mg; In a particular embodiment of the invention, the composition comprises, per unit dose, from 0.2 mg to 20 mg of crocins, preferably from 1 mg to 5 mg and more preferably from 2 mg to 4 mg. According to one embodiment of the invention, the Gardenia extract contains a mass fraction of crocins of between 0.1 and 10%, preferably between 0.5 and 8%, preferably between 1 and 5%, even more preferably between 1 and 3%. According to one embodiment of the invention, the Gardenia extract contains a mass fraction of crocetin of between 0.01 and 5%, preferably between 0.03 and 3%, even more preferably between 0.1 and 1%. According to a particularly advantageous embodiment of the invention, the cosmetic composition further comprises paprika and / or another source of carotenoids derived from plants, microorganisms, or microalgae, preferably an extract of paprika (Capsicum annuum), Haematoccus pluvialis rich in astaxanthin, marigold (Tagetes erecta) rich in lutein and zeaxanthin, tomato as a source of lycopene, Dunaliella salina, Xanthophyllomyces dendrorhous, and Blakeslea trispora as sources of carotenes. The present invention also relates to a cosmetic treatment method for coloring the skin, consisting of the administration of a cosmetic composition comprising an aqueous extract of Gardenia according to the invention. The present invention finally relates to a method for extracting Gardenia fruits. Gardenia fruits are extracted using a solvent consisting of water or a mixture of water and an organic solvent, such as an alcohol like ethanol or an ester like acetone. Extraction can be performed on whole fruits or on coarsely ground fruits. The addition of enzymes, such as pectinases, can improve extraction and / or filtration by thinning the extracted juices. Extraction can be carried out using a conventional method known to those skilled in the art, in a reactor, by ultrasound, or by microwaves at a temperature between 20°C and 100°C, depending on the presence or absence of enzymes. Extraction can be conducted at atmospheric pressure or under pressure with subcritical water. After solid-liquid separation, the filtrate is concentrated with water, sterilized, and then dried either as is or on a drying support such as maltodextrin or silica. Drying is carried out at temperatures below 80°C to avoid the degradation of crocins, molecules that are unstable at higher temperatures. It can be performed using techniques known to those skilled in the art, such as microwave drying or spray drying. The following examples illustrate the invention without limiting its scope. Example 1: Extraction process Whole gardenia fruits are extracted at 90°C with water for 2 hours. After solid / liquid separation, pectinases are added. The filtrate is concentrated with water to a 40% dry extract yield, sterilized, and then microwaved. The resulting dry aqueous extract is a red powder. The yield is approximately 25%. Crocin levels range from 0.1% to 10%, with an average crocin content of around 2%. Example 2: Pharmacological effects on a human skin expiatory model Due to the lack of cellular and animal pharmacological models, the inventors developed an ex vivo model to overcome the difficulties associated with the absorption of the active ingredients. Indeed, crocin cannot be absorbed without prior intestinal hydrolysis, and crocetin and its derivatives are poorly assimilated after passage. Protocol The aim of this study was to evaluate the staining effect of different extracts applied to human skin explants maintained for 72 hours. Survival was maintained in 6-well culture plates containing culture medium. These culture plates were placed in an incubator at 37°C with 5% CO2. The studies were performed on four donors. The color of each medium containing active ingredients or a control is assessed using the Dermoscope C-Cube Clinical Edition from PIXIENCE SAS. This represents the maximum achievable color, corresponding to 100% of the color mapping scale specific to each active ingredient. The color of each explant is measured using the Dermoscope C-Cube Clinical Edition. Prior to this measurement, the explant is placed in a solution of medium without active ingredients to rinse away any active ingredients present on the surface that have not yet penetrated the skin. Samples tested: Witness: cultural environment Paprika oleoresin (10% carotenoids) Aqueous extract of Gardenia (4% crocins) Chemically hydrolyzed aqueous extract of Gardenia (2.7% crocetin) Crocines (100%) Crocetin (87%), obtained by chemical hydrolysis of crocins. The culture medium chosen is a DMEM (Dulbecco's Eagle Modified Medium), supplemented with glutamine, antifungals and antibiotic, described in the study by Jacques et al. 2010 (Toxicol. In Vitro 24(5), 1426-34). The photos of the skin explants as well as the colorimetric differences, illustrated on the single attached figure, made it possible to show the significant coloring power of Crocetin, Gardenia and hydrolyzed Gardenia. Under these conditions, the coloring power of Paprika and crocins is lower than that of crocetin, Gardenia and hydrolyzed Gardenia. These studies provide proof of concept for the staining of explants using Gardenia extract, as well as hydrolyzed Gardenia extract and crocetin. These results were obtained on four donors, at different times and with different experimenters, thus validating the reproducibility of these findings. Example 3: Bioavailability of crocins Few studies have investigated the pharmacokinetic properties of crocins. The study in Example 2 demonstrated the staining power of crocins, but this result was obtained using human skin explants. However, the 2007 study by Xi et al. (Xi et al., Phytomedicine 14; 633-636, 2007) shows that crocins have a bioavailability of at least 20% in rats, suggesting even higher results in humans.

Claims

Demands Use of a cosmetic composition intended to color the skin, said cosmetic composition comprising as an active ingredient an aqueous extract of Gardenia. Use according to claim 1 characterized in that said extract is derived from the species Gardenia jasminoides. Use according to claim 1 or 2 characterized in that said extract contains a mass fraction of crocins of between 0.1 and 10%, preferably between 1 and 5%. Use according to any one of claims 1 to 3 characterized in that said composition is administered orally. Use according to any one of claims 1 to 4, characterized in that said composition further comprises paprika and / or β-carotene. Use according to any one of claims 1 to 5, characterized in that the aqueous extract of Gardenia is obtained by: - extraction from whole fruits in the presence of pectinases, - a solid-liquid separation, - sterilization of the filtrate, and - drying at temperatures below 80 °C. A cosmetic treatment method for coloring the skin consisting of the administration of a cosmetic composition according to claims 1 to 6.