USE OF COPAIFERA IN COSMETICS AND DERMATOLOGY

Abstract

The present invention relates to the use of an extract of Copaifera in cosmetics and dermatology in the treatment and / or prevention of alopecia as well as in the treatment of seborrhea.

Description

The present invention relates to the use of an extract of Copaifera in cosmetics and dermatology in the treatment and / or prevention of alopecia as well as in the treatment of seborrhea. EARLIER ART The genus Copaifera comprises 35 species, all trees native to tropical America, specifically Mexico, northern Argentina, and primarily Brazil. Within the region, more than twenty species are found, the most abundant being C. officinalis, C. reticulata, and C. multijuga. Copaifera officinalis is a tree found mainly in Brazil, Colombia, and Venezuela. It grows up to 25 meters tall and has reddish-brown wood. The leaves are compound, paripinnate with 2 to 10 leaflets, alternate or subopposite, apiculate, and unevenly rounded at the base. They are 3 to 8 cm long and 2 to 4 cm wide. The white flowers, generally sessile, are grouped in inflorescences 7 to 14 cm across. The fruits are small, swollen pods at maturity, 20-25 mm in diameter, hairless, with apiculate tips, containing an ovoid seed. Oleoresin is a substance obtained by making incisions in the bark of several Copaifera species. Located in anastomosing secretory canals of the secondary wood and pith, its extraction therefore requires very deep incisions in the trunk, allowing it to flow naturally from the tree. After steam distillation, or hydrodistillation, the oleoresin yields the Copaiba essential oil, renowned in perfumery. Copaiba oleoresin has been used medicinally since the 16th century by the indigenous people of Brazil. It has a long history of use in traditional Brazilian medicine, treating wounds and scars, reducing fever, acting as a urinary tract antiseptic, and treating leukorrhea and gonorrhea. Considered a general tonic, its indications included venereal diseases, respiratory illnesses, asthma, rheumatism, secondary skin lesions, and ulcers. In small doses, it acts as a direct stimulant on the stomach. Copaiba oleoresin reduces excessive mucus secretion caused by inflammation. Today, copaiba oleoresin is sold in capsule form in Brazilian pharmacies, where it is indicated for all types of internal inflammation and stomach ulcers.Applied topically, it is a powerful healing agent, both antiseptic and anti-inflammatory, aiding in the healing of even the most difficult wounds. Copaiba oleoresin is said to be very effective for joint pain, minor sprains, hematomas, and tendinitis. The oleoresin is applied directly to the skin. It is also used as a massage oil for sore or inflamed muscles and joints. Copaiba oleoresin, distilled or undistilled, is also used in cosmetics, in the manufacture of soaps, bath foams, detergents, and creams, and as a fixative in perfumery. The oleoresin is sometimes used as a flavoring in food. Copaiba oleoresin is also used as an artist's material, particularly in oil paint recipes and decorative ceramics. Oleoresin is a colorless, slightly viscous liquid that acquires an oily consistency and a greenish-yellow color over time. Its consistency and color vary slightly depending on the tree from which it is derived and the essential oil it contains. It has a strong, unpleasant odor and a bitter, acrid taste. Oleoresin is insoluble in water but completely soluble in alcohol and ether. The oleoresin of C. officinalis consists of 2 fractions that differ in their volatility; each fraction is characterized by distinct chemical compounds: - A "volatile" essential oil representing 50-90% of the oleoresin, which is mainly composed of sesquiterpenes. Among these sesquiterpenes, the most prominent are germacrene D, (E)-p-caryophyllene, p- and β-elemene, α-ylangene, α-gurjunene, and α-humulene. The minor sesquiterpenes are: α-cubebene, α-copaene, 7-epi-sesquithujene, cis- and trans-α-bergamotene, sesquisabinene-A and B, 4αH,10αH-guaia-1(5),6-diene, allo-aromadendrene, β-uurolene, α-amorphene, and p-selinene. bicycliosesquiphyllandrene, a-muurolene, p-bisabolene, y-cadinene, o-cadinene, cis-calamene, zonarene, cakina-1'4-diene, a-cadinene, a-calacorene, selina-3,7(11)-diene, germacrene B. This volatile oil is very clear, colorless, with a very strong odor and taste. - A "non-volatile" fraction representing 10-50% of the oleoresin, which is composed mainly of the following diterpenic acids and / or esters of diterpenic acids: copalic acid, copaiferolic acid, dimethyl ester of agathendioic acid, agathic acid, methyl ester of 3β-hydroxyanticopalic acid, hardwickiic acid, and 7α-acetoxyhardwickiic acid. This distillation residue is a viscous, aromatic, dark brown liquid. KR10-0863616 describes various cosmetic and therapeutic uses of the volatile fraction of Copaifera oleoresin, i.e., the essential oil. This document states that this essential oil possesses numerous anti-wrinkle, anti-inflammatory, hair growth stimulating, anti-obesity, antioxidant, immunosuppressive, and skin-whitening properties. Regarding the alleged anti-alopecia properties in This document, concerning this essential oil, reports that it is applied topically to the scalp of bald patients and that its effect on hair follicle regeneration is found to be equivalent to that observed with minoxidil. However, no effect on preventing hair loss has been demonstrated. Gomes da Silva et al. (Alternative Medicine Review; 17; 1; pp. 69-75) describe the anti-acne effect of Copaifera essential oil. In its introduction, this article confirms that the oleoresin, known for its numerous anti-inflammatory, antiseptic, and healing properties, is composed of two fractions: a sesquiterpene fraction (contained in the volatile essential oil) and a diterpene fraction (contained in the non-volatile fraction). In the tests conducted by Gomes da Silva et al., the essential oil (i.e., the sesquiterpene-rich volatile fraction) was applied to volunteers with type 1 acne (non-inflamed comedones). The conclusion of these tests is that the essential oil comprising the sesquiterpene volatile fraction of Copaiba oleoresin could have a use in the treatment of mild acne and the authors suggest a potential inhibitory role in the growth of Propionibacterium acnes in the anti-acne effect of this essential oil. Many studies have therefore focused on the volatile fraction of Copaifera oleoresin with regard to the therapeutic properties of this oleoresin. SUMMARY OF THE INVENTION The inventors have quite surprisingly demonstrated that Copaifera oleoresin, via its non-volatile fraction, presents particularly interesting and advantageous dermatological and dermo-cosmetic properties thanks to its inhibitory effect on the 5a-reductase enzyme. This property is relevant for uses in cosmetics and dermatology in the treatment or prevention of alopecia as well as in the treatment of seborrhea. DETAILED DESCRIPTION Alopecia is defined as the partial or total loss of hair. A hair's life cycle is governed by a process called the hair growth cycle, during which three phases occur. The anagen phase is a period of active and continuous growth, associated with intense metabolic activity at the level of the hair bulb. The catagen phase is characterized by a slowdown in mitotic activity. The hair undergoes involution, the follicle atrophies, and its dermal implantation appears increasingly higher. The final phase is the telogen phase, which corresponds to a resting period for the follicle, during which the hair eventually falls out, pushed out by a new hair. The hair growth cycle is complete, and another can begin. There are approximately 20 to 25 cycles per hair bulb in humans. With age, hair becomes thinner and its cycles shorter. Androgenetic alopecia is caused by an acceleration of the hair growth cycle (a shortening of the hair cycle duration), a phenomenon that initially leads to the appearance of miniaturized, or "vellus," hairs, and then to a premature depletion of hair renewal. Indeed, the duration of the anagen phase (growth phase) is shortened, going from several years (2 to 5 years) to a few months or even a few weeks (Whiting et al., J Investig Dermatol Symp Proc., 1999). The consequence is premature hair loss. It is now known that the mechanisms responsible for hereditary androgenetic alopecia (formerly called seborrheic alopecia) involve, among other things, a hormonal component with the overexpression of the androgen receptor (testosterone and DHT receptor) and increased activity of the 5-alpha reductase enzyme. This hormonal dysregulation leads to excessive production of dihydrotestosterone, the active metabolite of testosterone. At the level of the dermal papilla, this metabolite stimulates the production of hair cycle inhibitors, resulting in a shortened anagen phase. This forces the hair to transition too quickly into the telogen phase, not allowing the hair follicle enough time to produce quality keratin, and inevitably, after several cycles, depletion of the hair follicle's capacity to produce a hair shaft. This type of alopecia, caused by an excess of androgens, also affects women at the time of menopause (postmenopausal alopecia) or following androgen treatment. It begins at the temples and the crown. This hair loss is more diffuse and widespread than in men. The hair loss affects the entire scalp, evenly. An active 5 alpha reductase inhibitor thus makes it possible to treat and / or prevent hair loss in men and / or women. Seborrhea, on the other hand, is an excessive production of sebum by the sebaceous glands. Humans have approximately 2,000,000 sebaceous glands associated with 6,000,000 hairs. The distribution of sebaceous glands is uneven. The density of sebaceous glands reaches 300 to 900 glands per square centimeter on the face and scalp, while it is around 100 glands per square centimeter on the upper chest and back. The activity of the sebaceous gland is influenced by androgens. Androgens are only active under the influence of the 5-alpha reductase enzyme, which metabolizes them in the sebaceous gland, thus inducing sebum production. Hyperactivation of the 5-alpha reductase enzyme causes seborrhea. Seborrhea typically manifests in the mid-facial region (forehead, nose, chin), where the sebaceous glands are most numerous and largest. Seborrhea also affects the scalp, where it is most prevalent in the frontal, frontotemporal, and crown regions. Seborrhea causes aesthetic and dermatological problems such as seborrheic dermatitis. The skin appears shiny, the complexion is dull, and the pilosebaceous follicles are dilated. Furthermore, makeup does not adhere well to this type of oily skin. With seborrhea of ​​the scalp, the hair appears greasy and dull and is difficult to style. When the seborrhea is intense, it is described as oily, runny, and may be associated with a rancid odor. Seborrhea is often associated with androgenetic alopecia. An active ingredient that inhibits the activity of the 5-a reductase enzyme therefore makes it possible to reduce sebum secretion, treat seborrhea and resolve the aesthetic problems associated with seborrhea. Thus, the present invention relates, in a first embodiment, to an extract of Copaifera comprising or consisting of, as an active principle inhibiting 5-alpha reductase, a mixture of diterpenic acids and / or esters of diterpenic acids, for its use in the prevention and / or treatment of dermatological disorders selected from seborrhea and alopecia. In a second embodiment of the invention, Copaifera is chosen from the following plant species: Copaifera officinalis, Copaifera multijugla and Copaifera reticulata; used alone or in mixture. The Copaifera extract comprising a mixture of diterpenic acids and / or diterpenic acid esters according to the invention can be a refined Copaifera plant extract containing between 7.5 and 95% diterpenic acids and / or diterpenic acid esters. Advantageously, the Copaifera extract according to the invention comprises, or consists of, a Copaifera oleoresin containing at least 7.5% by weight of a mixture of diterpenic acids and / or diterpenic acid esters, particularly at least 15%, more particularly at least 20%, more particularly still at least 25%; relative to the total weight of the Copaifera oleoresin. The Copaifera extract according to the invention may comprise, or consist of, a Copaifera oleoresin enriched with a mixture of diterpenic acids and / or diterpenic acid esters containing, by weight percentage, between 48 and 90% of diterpenic acids and / or diterpenic acid esters, more particularly between 50 and 90%, more particularly between 60 and 90%, more particularly between 60 and 85%, more particularly between 80 and 90%; compared to the total weight of the enriched Copaifera oleoresin. The term "enriched," as used in the present invention, means that the oleoresin of the extract has an increased concentration of diterpenic acids and / or diterpenic acid esters compared to the native oleoresin—i.e., obtained directly from the tree—through various processes that increase the concentration of said diterpenic acids and / or diterpenic acid esters. This increase in concentration occurs preferentially for said acids and esters compared to other oleoresin compounds, which are either not present or only slightly concentrated. Enrichment can be achieved by a treatment using a process designed to concentrate the content of these diterpenic acids and / or diterpenic acid esters relative to other compounds and molecules. Such enrichment primarily involves the at least partial removal of the volatile fraction (i.e., essential oil). The mixture of diterpenic acids and / or diterpenic acid esters comprises at least 2, or at least 3, or at least 4, or at least 5, or at least 6, or at least 7 diterpenic acids and / or diterpenic acid esters selected from the group consisting of: copalic acid, copaiferolic acid, dimethium ester of agathendioic acid, agathic acid, methyl ester of 3β-hydroxyanticopalic acid, hardwickiic acid, and 7α-acetoxyhardwickiic acid. Preferably, it comprises the 7 diterpenic acids and / or diterpenic acid esters listed. Table 1: Molecular and structural formulas of the different diterpenic acids and / or esters of diterpenic acids Name Molecular formula m / z Structural formula Copalic acid C20H32O2 3O4 Z COOH Copaiferolic acid C20H32O3 320 TQ « / \ QM\ o -----Z.iuü1 „ O \-------------- / X / O Dimethyl ester of agathendioic acid C22H34O4 362 Agathic acid C20H30O4 334 Methyl ester of 3-beta-hydroxyanticotropic acid C20H30O4 334 Hardwickian acid C20H28O3 316 7-alpha acetoxyhardwickian acid C22H30O5 374 p3 iq VK i H 17 31^ si 1 r^c,;8 U: R s H Preferably, the mixture of diterpenic acids and / or diterpenic acid esters comprises all of the following diterpenic acids and / or diterpenic acid esters: copalic acid, copaiferolic acid, dimethyl ester of agathendioic acid, agathic acid, methyl ester of 3beta-hydroxyanticopalic acid, hardwickiic acid, 7 alpha acetoxyhardwickiic acid. The Copaifera extract according to the invention, consisting of an oleoresin, comprises, by weight percentage, between 7.5 and 40% of the 7 diterpenic acids and / or esters of diterpenic acids mentioned above, preferably between 10 and 30%. The Copaiefera extract according to the invention, consisting of an enriched oleoresin, comprises, by weight percentage, between 48 and 90% of the 7 diterpenic acids and / or esters of diterpenic acids mentioned above, preferably between 60 and 85%. Table 2 Product Name Mass Content in Loleoresin (%) Mass Content of Diterpene Fraction (%) Copalic Acid 3 to 13 15 to 50 Hardwickian Acid 0.5 to 1.5 2 to 15 Copaiferolic Acid 1 to 6 10 to 30 Agathic Acid and Methyl Ester of 3β-Hydroxyanticopalic Acid 1 to 6 8 to 30 Dimethyl Ester of Agathendioic Acid 1 to 6 10 to 30 7-Alpha Acetoxyhardwickian Acid 1 to 8 3 to 15 In a particular embodiment, the extract according to the invention comprises or consists of the non-volatile fraction of Copaifera oleoresin. In another embodiment, the extract according to the invention comprises or consists of a mixture of diterpenic acids and / or esters of diterpenic acids. This "non-volatile" fraction of Copaifera oleoresin comprises the mixture of diterpenic acids and / or diterpenic acid esters and can be obtained after total or partial, preferably total, removal of the essential oil, particularly by hydrodistillation. This non-volatile fraction comprises at least 80% and preferably between 80 and 90% by weight of diterpenic acids and / or diterpenic acid esters. This represents an extract consisting of enriched oleoresin with maximal enrichment. The mixture of diterpenic acids and / or diterpenic acid esters can also be obtained from a Copaifera oleoresin, or from the "non-volatile" fraction of the Copaifera oleoresin; in particular by liquid-liquid extraction until a mixture is obtained with a concentration of diterpenic acids and / or acid esters. diterpenic acids comprising between 50 and 100%, particularly between 60 and 100%, and even more particularly between 80 and 100% by weight of diterpenic acids and / or diterpenic acid esters relative to the total weight of the liquid fraction obtained after extraction and removal of the extraction solvent. This liquid fraction obtained after extraction and removal of the solvent represents said mixture. The present invention further relates to a dermatological or dermo-cosmetic composition comprising an extract of Copaifera according to the invention and as described above, with at least one dermatologically or cosmetically acceptable excipient, for its use in the treatment of alopecia and / or seborrhea. The invention further relates to a composition according to the present invention for use in the treatment of alopecia and / or seborrhea, in a form suitable for topical administration. Treatment or prevention of alopecia may involve slowing down hair loss. Seborrhea can be categorized as either skin seborrhea or scalp seborrhea. Topical administration can be administration to the hair and / or scalp and / or skin. The invention further relates to a composition according to the present invention for use in the treatment of alopecia and / or seborrhea, in a form suitable for oral administration. A composition according to the invention is characterized in that it comprises from 0.05% to 10% by weight of the extract according to the invention, relative to the total weight of the composition. The invention further relates to the use of an extract or according to the invention for the treatment and / or prevention of seborrhea and / or alopecia. The invention further relates to an anti-seborrheic composition comprising a Copaifera extract according to the invention and as described above, with at least one dermatologically or cosmetically acceptable excipient. The preferred anti-seborrheic composition is one suitable for topical administration. The invention further relates to an anti-alopecia composition comprising a Copaifera extract according to the invention and as described above, with at least one dermatologically approved excipient. or cosmetically acceptable. The preferred anti-alopecia composition is one suitable for topical administration. The composition according to the invention, as described above, is characterized in that the quantity of Copaifera extract is between 0.05% and 10% by weight relative to the total weight of the composition. The quantity of extract may be adjusted according to the nature of the extract, i.e., whether it is crude oleoresin, enriched oleoresin, or a mixture of diterpenic acids and / or diterpenic acid esters. This quantity may be between 0.05% and 10% by weight, more particularly between 1% and 10%, between 2% and 7.5%, or between 3% and 6%, for example. In another embodiment, the present invention also relates to a cosmetic method for treating or preventing a disorder selected from oily skin, shiny skin, oily hair, oily scalp, comprising the topical application of an extract according to the invention or a composition according to the invention. In another embodiment, the present invention also relates to a cosmetic method for mattifying seborrheic skin. The extract according to the invention can be associated or mixed with a lipid-based support or vehicle in order to standardize the content of diterpenic acids and / or diterpenic acid esters in the composition according to the invention. The lipid support or vehicle can be an oil, in particular a dermatologically or cosmetically acceptable oil. In the present invention, "dermatologically or cosmetically acceptable" means something useful in the preparation of a dermatological or cosmetic composition, which is generally safe, non-toxic and neither biologically nor otherwise undesirable, and which is acceptable for dermatological or cosmetic use, in particular by topical application. The compositions according to the invention are advantageously intended for topical application, in particular on the skin. The compositions according to the invention may thus be presented in the forms which are usually known for topical administration, namely in particular lotions, foams, gels, dispersions, emulsions, sprays, serums, masks or creams, with excipients allowing in particular skin penetration in order to improve the properties and accessibility of the active ingredient. Advantageously, it will be a cream. These compositions generally contain, in addition to the extract according to the present invention, a physiologically acceptable medium, usually water-based or solvent-based, for example alcohols, ethers, or glycols. They may also contain surfactants, complexing agents, preservatives, stabilizing agents, emulsifiers, thickeners, gelling agents, humectants, emollients, trace elements, essential oils, perfumes, colorants, mattifying agents, chemical or mineral filters, moisturizing agents, thermal waters, etc. These compositions may also contain other active ingredients leading to a complementary or possibly synergistic effect. (simultaneously, separately or spread out over time, with) PHARMACOLOGICAL EVALUATION The following example illustrates the invention without limiting its scope. Example 1: Effects of different compounds on the activity of 5a-reductase of fibroblasts from human dermal papilla follicles. The objective of this study was to evaluate a possible inhibitory activity of different compounds on 5α-reductase. Materials and methods The study was performed on human cells derived from donor dermal papilla follicles. This model is of interest because dermal papillae express the 5alpha2 isoform, as does prostate tissue. The cells were seeded in 24-well plates and cultured for 24 hours in DMEM culture medium supplemented with L-glutamine (2 mM), penicillin (50 U / ml), streptomycin (50 pg / ml), and Fetal Calf Serum (10%) under standard culture conditions (37°C and 5% CO2). The culture medium was then replaced with DMEM analysis medium supplemented with L-glutamine (2 mM), penicillin (50 U / ml), streptomycin (50 pg / ml), and Fetal Calf Serum (1%). This analysis medium may or may not contain (control conditions) the products to be tested and a reference compound, finasteride (10pM), for 24 hours of pre-incubation.The cells were then treated with an analytical medium containing testosterone [C14] and either containing (control conditions) the products to be tested or reference, and the cells were incubated for 24 hours under these conditions. After incubation, the supernatants were collected for testosterone metabolism analysis. All experiments were performed three times. Steroid molecules were extracted from the supernatants with a chloroform / methanol mixture. The organic phase was collected, and the different molecular species (testosterone metabolites) were separated by thin-layer chromatography using a solvent system containing dichloromethane. ethyl acetate and methanol. Autoradiography was performed on the chromatography and the transformed testosterone was estimated by densitometric analysis. Thus, the metabolism of testosterone into dihydrotestosterone accounts for 5a-reductase activity, and is evaluated by the dihydrotestosterone / testosterone ratio. Results A first set of experiments highlighted the effects of Copaifera officinalis oleoresin (Table 3 below). Surprisingly, the inventors demonstrated significant and reproducible inhibition of 5α-reductase by Copaifera officinalis oleoresin; this inhibition even appeared to be concentration-dependent. The significant inhibition of this enzyme by finasteride further validated these experiments. Table 3: Effects of Copaifera officinalis oleoresin and finasteride on testosterone metabolism / dihydrotestosterone production (5α-reductase activity; n=3) Finasteride Oleoresin (C. officinalis) Control 10 pM 10 pg / ml 30 pg / ml 100 -77% -15% -27% ** P<0.01 * P<0.05 ** P<0.01 The statistical study is carried out versus the control group (Dunnett's test). The oleoresin tested was prepared according to the method described in example a. For comparison, an extract of Serenoa repens, an extract of Curcubita pepo and the compound glyceryl laurate were also tested in one of these experiments. At 10 pg / ml, the Serenoa repens extract does not induce significant inhibition of 5α-reductase. However, at 20 pg / ml, this extract induces inhibition of 23%, reaching statistical significance (p<0.05 versus control). A significant inhibition of 17% was obtained for a Curcubita pepo extract tested at 100 pg / ml. A significant inhibition of 19% was obtained for the glyceryl laurate tested at 40pg / ml. A second series of experiments was conducted to evaluate whether the inhibitory activity on 5α-reductase was mediated by the non-volatile fraction or rather by the volatile fraction corresponding to the essential oil. The results are summarized in Table 4 below. The preparation of the volatile and non-volatile fractions is carried out according to the method described in example c with the diethyl ester as the non-polar solvent. Table 4: Effects of non-volatile and volatile fractions from Copaifera officinalis oleoresin on testosterone metabolism / dihydrotestosterone production (5α-reductase activity) Control Non-volatile fraction Volatile fraction 0.3 pg / ml 1 pg / ml 3 pg / ml 7.7 pg / ml 23.1 pg / ml 100 0 -6% -14% +2 +9 P=NS P=NS * P<0.05 P=NS P=NS The statistical study is carried out versus the control group (Dunnett's test). It appears that the activity of Copaifera officinalis oleoresin is mediated by the non-volatile fraction; indeed, no activity of the volatile fraction was observed. Inhibition of 5α-reductase is only 14% at 3 pg / mL (10 times less concentrated than the oleoresin), but this reduction reaches statistical significance (p<0.05). A third series of experiments was conducted to demonstrate that other Copaifera species, notably C. multijuga, also exhibited interesting activity in inhibiting 5α-reductase. The researchers focused on the non-volatile fraction, which carries the inhibitory activity. The results are summarized in Table 3 below. Table 5: Effects of diterpene fractions from Copaifera multijuga resin on testosterone metabolism / dihydrotestosterone production (5α-reductase activity; n=2) Control Non-volatile fraction Copaifera multijuga 1 pg / ml 10 pg / ml 100 0 -31% P=NS ** P<0.01 The statistical study is carried out versus the control group (Dunnett's test). The preparation of the volatile and non-volatile fractions is carried out according to the method described in example c with the diethyl ester as the non-polar solvent. These results clearly show that several Copaifera species are of interest. Indeed, the non-volatile fraction of the C. multijuga species achieves 31% inhibition of 5α-reductase at 10 pg / ml. These results lead to the conclusion that Copaifera oleoresin exhibits highly interesting inhibitory activity on 5α-reductase. This activity is mediated by the non-volatile fraction of the resin. Furthermore, the inventors have also demonstrated that this activity is observed in several Copaifera species. EXAMPLES - Preparation of oleoresin Example a: The bark of the trunks of Copaifera officinalis and / or Copaifera multijuga and / or Copaifera reticulata trees is cut to extract the oleoresin. This is then homogenized and stabilized under nitrogen. The active ingredient is composed of 100% crude oleoresin from the trunk of Copaifera officinalis and / or Copaifera officinalis and / or Copaifera. multijuga and / or Copaifera. Reticulata. LCMS analysis of a Copaifera Officinalis oleoresin: Each sample was analyzed by UHPLC-QTOFMS according to a classical linear gradient. Separation on Waters Acquity UHPLC system. - 100 x 2.1 mm, 1.7 µm Acquity BEH C18 column equipped with a pre-column - Mobile phase: Mobile phase A: LCMS grade water + 0.1% formic acid Mobile phase B: Acetonitrile LCMS grade + 0.1% formic acid Gradient: Time (min) %A %B 0-0.5 50 50 0.5-4 50^ 40 50 —> 60 4-12 40^ 1 60 ^99 12-15 1 99 15-15.5 1 ^50 99^50 15.5-19 50 50 Acquisitions: UV 220 nm Structure m / z Content in oleoresin (% mass relative to oleoresin weight) Copalic acid 304 5.69 Hardwickian acid 316 0.61 Copaiferolic acid 320 2.90 Agathic acid and methyl ester of 3 beta-hydroxyanticopalic acid 334 2.35 Dimethyl ester of agathendioic acid 362 2.92 7α-acetoxyhardwickiic acid 374 0.79 - Preparation of non-volatile fraction. - Example b: The oleoresin obtained according to the preceding example (a) is suspended in 10 volumes of water heated to 100 °C for 4 hours to perform hydrodistillation. The volatile essential oil is recovered by condensation. After hydrodistillation, the distillation residue is collected. After drying by freeze-drying or other drying methods, the residue constitutes the non-volatile fraction. - Example c: One volume of Copaifera oleoresin obtained according to the preceding example (a) is diluted in 8 to 10 volumes of a lipophilic solvent immiscible with water (such as diethyl ether or ethyl acetate). This solution is extracted by liquid-liquid extraction with a 5% sodium hydroxide (NaOH) solution. The operation is repeated three times with 4 to 5 volumes of 5% NaOH. The lower phase (basic aqueous phase) is acidified by the addition of 1 N hydrochloric acid (HCl) and then extracted by liquid-liquid extraction with a nonpolar solvent immiscible with water (such as diethyl ether or ethyl acetate). The ethyl acetate phase is washed with water and then dehydrated over Na₂SO₄. After removal of the solvent by rotary evaporator or other drying methods, the dry residue the obtained corresponds to the mixture of diterpenic acids and / or esters of diterpenic acids according to the invention. Structure m / z Mass content in the non-volatile fraction Copalic acid 304 28.45 Hardwickiic acid 316 3.05 Copaiferolic acid 320 14.52 Agathic acid and methyl ester of 3 beta-hydroxyanticopalic acid 334 11.77 Dimethyl ester of agathendioic acid 362 14.58 7α-acetoxyhardwickiic acid 374 3.96 - Example: Anti-hair loss hair composition Copaifera Officinalis oleoresin according to example a) from 0.05 to 10% DEXPANTHENOL 0.3 to 1% ISOPROPYL ALCOHOL 1 to 5% PPG-26-BUT.-26 / PEG-40 2 to 10% ETHYL ALCOHOL 10 to 40% PERFUME 0.2 to 1% WATER Qsp - Example: Anti-seborrheic composition Non-volatile fraction according to example b: from 0.05 to 10% Glycerin: 2% to 5% Phenoxyethanol: 0.3 to 0.5% Na2EDTA: 0.1 to 0.2% Polyacrylate-13, Polyisobutene, Polysorbate 20, and water: 1% to 2% Glyceryl stearate and PEG-100 stearate: 2 to 5% Cyclopentasiloxane: 3% to 5% Cetyl alcohol: 1% to 2% Glycerol tri-2-ethylhexanoate: 2% to 3% Dicapryl carbonate: 2% to 3% Polymethylacrylate: 2% to 3% Perfume: 0.1% to 1% Water Qsp

Claims

DEMANDS 1. Copaifera extract comprising, as an active ingredient inhibiting 5-alpha reductase, a mixture of diterpenic acids and / or esters of diterpenic acids, for its use in the prevention and / or treatment of alopecia.

2. Extract according to claim 1, characterized in that the Copaifera is selected from the following plant species: Copaifera officinalis, Copaifera multijugla and Copaifera reticulata; used alone or in mixture.

3. Extract according to one of claims 1 or 2, characterized in that it contains between 7.5 and 95% of diterpenic acids and / or esters of diterpenic acids.

4. Extract according to any one of claims 1 or 2, characterized in that this extract comprises a Copaifera oleoresin containing at least 7.5% by weight of a mixture of diterpenic acids and / or esters of diterpenic acids, particularly at least 15%, more particularly at least 20%, more particularly still at least 25%; relative to the total weight of the Copaifera oleoresin.

5. Extract according to claim 4, characterized in that this extract comprises a Copaifera oleoresin enriched in a mixture of diterpenic acids and / or diterpenic acid esters containing, in % by weight, between 48 and 90% of diterpenic acids and / or diterpenic acid esters, more particularly between 50 and 90%, more particularly between 60 and 90%, more particularly between 80 and 90%; relative to the total weight of the enriched Copaifera oleoresin.

6. Extract according to any one of claims 1 to 5, characterized in that the extract comprises or consists of the non-volatile fraction of Copaifera oleoresin.

7. Extract according to any one of claims 1 to 5, characterized in that the extract comprises or consists of a mixture of diterpenic acids and / or esters of diterpenic acids.

8. Extract according to any one of claims 1 to 7, characterized in that the mixture of diterpenic acids and / or esters of diterpenic acids comprises at least 2, or at least 3, or at least 4, or at least 5, or at least 6, or at least 7 diterpenic acids and / or esters of diterpenic acids selected from the group consisting of: copalic acid, copaiferolic acid, dimethyl ester of agathendioic acid, agathic acid, methyl ester of 3beta-hydroxyanticopalic acid, hardwickiic acid, 7 alpha acetoxyhardwickiic acid.

9. Extract according to any one of claims 1 to 8, characterized in that the mixture of diterpenic acids and / or esters of diterpenic acids comprises the following diterpenic acids and / or esters of diterpenic acids: copalic acid, copaiferolic acid, dimethyl ester of agathendioic acid, agathic acid, methyl ester of 3beta-hydroxyanticopalic acid, hardwickiic acid, 7 alpha acetoxyhardwickiic acid.

10. Dermatological composition comprising an extract of Copaifera according to any one of claims 1 to 9, with at least one dermatologically acceptable excipient, for its use in the treatment of alopecia.

11. Composition according to claim 10, characterized in that the quantity of Copaifera extract is between 0.05% and 10% by weight relative to the total weight of the composition.

12. Composition according to claim 10, for its use in slowing down hair loss.

13. Composition for its use according to any one of claims 10 to 12, in a form suitable for topical administration.

14. Anti-alopecia composition comprising an extract of Copaifera according to any one of claims 1 to 9, with at least one dermatologically or cosmetically acceptable excipient.