EP4009997A1

EP4009997A1 - Extract of silybum marianum (l.) gaertn. akenes for promoting hair growth

Info

Publication number: EP4009997A1
Application number: EP20754703.5A
Authority: EP
Inventors: Jean-Hilaire Saurat; Daniel BACQUEVILLE; Hélène DUPLAN
Original assignee: Pierre Fabre Dermo Cosmetique SA
Current assignee: Pierre Fabre Dermo Cosmetique SA
Priority date: 2019-08-06
Filing date: 2020-08-06
Publication date: 2022-06-15
Also published as: MX2022001639A; US20220331387A1; BR112022001032A2; WO2021023820A1; FR3099699A1; CN114206363A; CN114206363B

Abstract

The present invention relates to an extract of Silybum marianum (L.) Gaertn. akenes and to compositions containing said extract for application in the fields of cosmetics and dermatology for promoting hair growth.

Description

SILYBUM MARIANUM (L.) GAERTN AKENES EXTRACT. TO PROMOTE HAIR GROWTH TECHNICAL FIELD OF THE INVENTION

The present invention relates to an extract of achenes from Silybum marianum (L.) Gaertn., As well as to compositions containing this extract for application in the fields of cosmetics and dermatology for promoting hair growth. STATE OF THE ART

Hair care, not only for cosmetic purposes but also to prevent hair loss and to regenerate it, has always required the spirit of research. Many theories have attempted to shed light on the aetiology of hair loss in cases of baldness, alopecia, alopecia areata, etc., blaming them on an increase in the tension of the tissue on the sphere. cranial, reduced blood supply, or certain endocrine or nervous disorders.

The hair follicle is a mini-organ anchored in the skin up to the hypodermis, whose main function is the production of a hair shaft. The distribution of hair follicles is established during growth in utero and their number is determined genetically. The hair follicle is a dynamic structure that produces hair during the cycle of tissue growth and remodeling. This cycle is broken down into three phases:

A growth phase (anagen), the cells of the dermal papilla (fibroblasts) send a signal to the stem cells of the bulb which allows their proliferation. Cells will transform and envelop the dermal papilla to form the hair's sulfur matrix. They divide and differentiate into follicular keratinocytes, cells responsible for the structure of the hair. For the hair to be well structured, these keratinocytes need sulfur proteins, vitamin B6 and various minerals such as zinc and magnesium. The duration of this phase determines the length of the hair and depends on the proliferation and differentiation of the cells of the matrix at the base of the follicle.

A phase of regression (catagen), the matrix dies and therefore the papilla skin is no longer in contact with this matrix. There is no more exchange between the cells. The follicle and the dermal papilla ascend towards the epidermis.

A resting phase (telogen), the cells of the dermal papilla and bulb are intact and inactive. The hair falls out. For a new hair to grow, the cycle must be restarted.

The hair is therefore constantly renewed and of the 100,000 to 150,000 hairs in a head of hair, the majority is in the growth phase. There is a normal and physiological loss of hair in the range of 60 to 100 per day for healthy hair. Beyond that, the fall is said to be pathological, whether it is occasional or installed.

The term alopecia refers to the partial or general lack of hair on the head. Effluvium is excessive hair loss.

Many factors can be involved in alopecia such as genetic factors, age, gender, illnesses, stress, hormonal problems, side effects of drugs, scarring. It is possible to distinguish several forms of alopecia:

Hereditary androgenetic alopecia is the most common; premature hair loss occurs in genetically predisposed subjects and particularly affects men. It is manifested by a decrease in hair volume, even baldness and affects 50% of men over 50 years old.

Postmenopausal alopecia is the most common cause of baldness in women. Hair loss is more diffuse and extensive in women than in men. Diffuse female alopecia is a disorder that often starts at menopause and affects about 40% of women over the age of 70. The term diffuse illustrates that, unlike men, hair loss affects the entire scalp, evenly.

Acute or reactive alopecia, it can be linked to drug treatment (including cancer treatments), stress, childbirth, severe dietary deficiencies, iron deficiency, hormonal disorders, it is a fall simultaneous and diffuse of a large amount of hair.

Scarring alopecia, it can be caused by skin problems (tumor, burn, alopecia areata), acute irradiation, lupus erythematosus or parasites (ringworm, lichen).

Alopecia areata, it seems to be of autoimmune origin and is characterized by an involvement in more or less large plaques and in one or more places.

Congenital alopecia, rare, it corresponds to the absence of a root or to hair abnormalities (mutations).

The term alopecia also covers a whole family of damage to the hair follicle, the final consequences of which are permanent, partial or general loss of hair.

We distinguish diffuse hair loss and localized hair loss.

Diffuse hair loss: common alopecia, telogen effluvium, anagen effluvium, alopecia areata. Among diffuse hair loss, the most frequent are common alopecia (male and female androgenetic alopecia) and G telogen effluvium (after high fever, pregnancy, medication or severe diet).

Localized hair loss: androgenetic alopecia, alopecia areata, scarring alopecia, tumors. Localized hair loss is observed in the context of male androgenetic alopecia (gulfs, tonsure), alopecia areata, alopecia induced by traction (trichotillomania, braiding and straightening) or cicatricial alopecia (central cicatricial alopecia centrifugal, postmenopausal fibrosing frontal alopecia). Mention may also be made of inflammatory cicatricial alopecia, in particular folliculitis including dissecting folliculitis and decalvating folliculitis. Tumors and growths of the skin are also accompanied by localized hair loss (sebaceous hamartoma, basal cell carcinoma, squamous cell carcinoma).

Alopecia is essentially linked to a disturbance in hair renewal which initially results in the acceleration of the frequency of cycles at the expense of the quality of the hair and then of its quantity. The most frequent phenomenon is a reduction in the duration of the growth phase (anagen phase) in connection with an arrest of cell proliferation. The consequence is a premature induction of the catagen phase and a greater number of hair follicles in the telogen phase and therefore a greater loss of hair. To fight against alopecia, it is therefore necessary to restart the hair cycle, for example by activating the anagen phase.

To date, various products have been proposed to fight against alopecia, and in particular to induce or stimulate hair growth. Most of them combine several active ingredients capable of providing a beneficial action on the biological parameters involved in hair loss. Among the active principles most commonly encountered, we can cite by way of example: vitamins such as vitamins A, E, B5, B6, C, H, and PP; trace elements such as zinc, copper, magnesium, silicon; protein derivatives such as peptides, sulfur-containing amino acids (methionine, cystine, cysteine or derivatives type); essential oils or extracts of plant origin of a lipophilic or hydrophilic nature, the list of which is not exhaustive; antifungal agents such as piroctone olamine, undecylenic derivatives, cyclopriroxolamine; synthetic chemical molecules known for their specific action on androgen receptors or on the activity of 5-α reductases. Minoxidil or 2,4-diamino-6-piperidinopyrimidine 3-oxide is now the reference in the treatment of androgenetic alopecia. Despite the many theories raised about its mechanism of action, it is not clearly understood. In addition, its effectiveness remains limited, because even if a stabilization of hair loss is observed in many clinical cases, a resumption of the alopecia process is observed as soon as the treatment is stopped. Its restrictive daily use is probably the cause of undesirable side effects noted in patients using it long term, such as localized skin reactions or systemic effects. Furthermore, compositions comprising very diverse active agents are proposed in hair regrowth, these active agents possibly being derivatives of 2,4-diaminopyrimidine 3-oxide such as those described in patent application EP0522964. Clinical studies have demonstrated that PGF2a analogues have the property of inducing the growth of hair and eyelashes in humans and animals (Johnstone, Am J Opht, 124 (4), 544-547, 1997). In humans, tests carried out on the scalp have shown that a prostaglandin E2 analogue, viprostol, has the property of increasing hair density. Application WO98 / 33497 describes pharmaceutical compositions containing prostaglandins or prostaglandin derivatives intended to promote hair growth.

Thus, despite the many options currently available, consumers still need new products to promote hair regrowth, that are natural and respectful of the environment, while being as effective as chemical actives.

Recent advances in understanding the biology of the hair cycle involve early and late type stem cells (Mesler et al. Cell Reports 79, 809-821, 2017). In addition, these early stem cells have as progeny cells which produce certain keratins with essential functional properties in preventing hair loss. Of these keratins, K75 is the first to be produced, and its genetic deficiency in humans leads to pathological hair loss. This protein is characteristic of cells forming the companion layer of the inner sheath of the root of hair follicles (Gu and Coulombe J Invest Dermatol, 2007, 127 (5): 1061-73). In the study described by Sperling et al. (J Cutan Pathol 2010, 37: 243-248), it is shown that the expression of K75 decreases sharply during the process of early desquamation of the inner sheath of the root of hair follicles. As this desquamation is a histological marker of alopecia, it turns out that this K75 protein undoubtedly plays a key role in the mechanisms of alopecia.

The scientific name Silybum marianum (L.) Gaertn. designates a plant belonging to the Asteraceae family, annual or biennial, with a robust stem, which can reach more than one meter in height. Its large, shiny, alternate leaves without stipule are mottled white and edged with hard, pointed thorns. The flowers are grouped in terminal heads, often solitary. They are surrounded by large, thorny bracts with very sharp ends. The flowers, tubular, five-lobed, are purplish-purple in color. The fruits are shiny achenes, black or marbled with yellow, topped with a crest with denticulate bristles in a ring at their base. The vernacular name of this plant is Milk Thistle.

Achene (often mistakenly referred to as seed in the literature) of Silybum marianum (L.) Gaertn. and its preparations are traditionally used orally, in the symptomatic treatment of functional digestive disorders attributed to hepatic origin.

The main active ingredient in achene from Silybum marianum (L.) Gaertn. is silymarin, a mixture of several flavonolignans (mainly silybin, isosilybin, silychristin, and silydianin). Achenes contain up to 3% by weight of silymarin. They also consist of oil (20-30% by weight), mucilages and proteins.

Silymarin has been the subject of numerous studies (in vitro, in vivo and clinical) which have demonstrated its antioxidant, hepatoprotective, digestive and anti-inflammatory properties.

Currently, extracts of achenes from Silybum marianum (L.) Gaertn. titrated in silymarin are present in several pharmaceutical preparations intended for the treatment of various liver and biliary disorders, such as Legalon®.

Silybin (a major silymarin flavonoid) has also been the subject of a very recent study in hair growth (Cheon et al., J Microbiol Biotech 29 (2), 321-329, 2019) via the Akt Wnt / -catenine signaling.

Oil from Silybum marianum (L.) Gaertn. rich in omega 6 and vitamin E, is mainly used in cooking. It is conventionally obtained from achenes by cold pressing. Studies on the antioxidant and hepatoprotective properties of such milk thistle oil, administered orally, have however been carried out in vivo on rats or mice (Zhu et al. Pharmacogn Mag, 10 (Suppl 1) S92- S99, 2014). Application WO2018 / 002338 describes an extract of achenes from Silybum marianum (L.) Gaertn. poor in silymarin which has interesting properties for the treatment of acne, seborrhea, rosacea or seborrheic dermatitis.

Thus, to date, no bibliographic data mentions only an extract of achenes from Silybum marianum (L.) Gaertn. low in silymarin may have activity in hair regrowth and therefore be useful in the prevention and / or treatment of alopecia. SUMMARY OF THE INVENTION

Unexpectedly and surprisingly, the applicants have demonstrated that an extract of achenes from Silybum marianum (L.) Gaertn. poor in silymarin has pharmacological activities of interest in the field of treatment and / or prevention for combating hair loss, in particular by promoting their growth. Indeed, the inventors have demonstrated that an extract of achenes from Silybum marianum (L.) Gaertn. poor in silymarin induces an increase in the expression of the protein Keratin 75 in the follicles. Thus the extract of achenes from Silybum marianum (L.) Gaertn. poor in silymarin will help to delay and prevent hair loss and extend the hair's life cycle.

According to a first aspect, the invention relates to an extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract for its use for promoting hair growth and in particular for treating or preventing alopecia such as alopecia androgenetic, reactive alopecia, postmenopausal alopecia or alopecia areata, or else cicatricial alopecia, in particular folliculitis and preferably dissecting folliculitis.

The invention also relates to the use, in particular cosmetic or dermatological, of an extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract to promote hair growth and in particular to treat or prevent alopecia such as androgenetic alopecia, reactive alopecia, postmenopausal alopecia or alopecia areata, or else cicatricial alopecia, in particular folliculitis and preferably dissecting folliculitis.

The invention also relates to the use of an extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract for the preparation of a cosmetic or dermatological composition intended to promote hair growth and in particular to treat or prevent alopecia such as androgenetic alopecia, reactive alopecia, post-menopausal alopecia or alopecia areata, or else cicatricial alopecia, in particular folliculitis and preferably dissecting folliculitis.

The invention also relates to a method, in particular cosmetic or dermatological, for promoting hair growth and in particular for treating or preventing alopecia such as androgenetic alopecia, reactive alopecia, post-menopausal alopecia or alopecia areata, or else cicatricial alopecia, in particular folliculitis and preferably dissecting folliculitis, comprising the administration to a person in need thereof of an effective amount of an extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract.

According to a second aspect, the present invention relates to a dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, with at least one dermatologically or cosmetically acceptable excipient for its use for promoting hair growth and in particular for treating or preventing alopecia such as androgenetic alopecia, reactive alopecia, postmenopausal alopecia or alopecia areata, or else cicatricial alopecia, in particular folliculitis and preferably dissecting folliculitis.

The invention also relates to the use, in particular cosmetic or dermatological, of a dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, with at least one dermatologically or cosmetically acceptable excipient, to promote hair growth and in particular to treat or prevent alopecia such as androgenetic alopecia, reactive alopecia, post-menopausal alopecia or alopecia areata, or else cicatricial alopecia, in particular folliculitis and preferably dissecting folliculitis. The invention also relates to the use of a dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, with at least one dermatologically or cosmetically acceptable excipient, for the preparation of a medicinal product intended for promote hair growth and in particular to treat or prevent alopecia such as androgenetic alopecia, reactive alopecia, post-menopausal alopecia or alopecia areata, or even cicatricial alopecia, in particular folliculitis and preferably dissecting folliculitis .

The invention also relates to a method, in particular cosmetic or dermatological, for promoting hair growth and in particular for treating or preventing alopecia such as androgenetic alopecia, reactive alopecia, post-menopausal alopecia or alopecia areata, or scarring alopecia, in particular folliculitis and preferably dissecting folliculitis, comprising the administration to a person in need thereof of an effective amount of a dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, with at least one dermatologically or cosmetically acceptable excipient.

According to a third aspect, the present invention relates to a method of dermatological treatment of an area of the scalp devoid of hair, comprising the topical application to the area of the scalp devoid of hair of an extract of achenes from Silybum marianum ( L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract or of a dermatological composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, with at least one dermatologically acceptable excipient, prior to or concomitantly with a hair transplant or with a treatment scalp medical treatment such as treatment with platelet rich plasma or hair mesotherapy. DETAILED DESCRIPTION OF THE INVENTION

Definitions

In the present description, the plant Silybum marianum (L.) Gaertn. may be referred to for short by the term Silybum marianum.

For the purposes of the present invention, the term “silymarin” is understood to mean a purified extract of achenes from Silybum marianum (L.) Gaertn. predominantly comprising (at least 95% by weight) a mixture of the following four flavonolignans: silybin, isosilybin, silychristin and silydianin (Kuki et al., Chromatographia 75: 175-180, 2012). A silymarin content of less than 0.2% by weight therefore means that the total amount of the constituents of silymarin is less than 0.2% by weight. Such a content can be determined in particular by HPLC (High Performance Liquid Chromatography) or UPLC (Ultra High Performance Liquid Chromatography) by calculating the total area of the peaks corresponding to all the constituents of silymarin, in particular by using a reference silymarin sample, which can be obtained for example from Sigma Aldrich, to determine the position of these peaks.

By "silybin", also called silibinin in the art, is meant, within the meaning of the present invention, the four diastereoisomers silybin A, silybin B, 2,3-cis-silybin A and 2,3-cis-silybin B.

By “isosilybin” is meant, within the meaning of the present invention, the two diastereoisomers isosilybin A and isosilybin B.

By “silychristin” is meant, within the meaning of the present invention, the two diastereoisomers silychristin A and silychristin B. By “approximately” is meant in the present description that the value concerned may be less than or greater than 10%, in particular of 5%, in particular 2%, more particularly 1%, to the indicated value.

By "dry extract" is meant, within the meaning of the present invention, an extract devoid of extraction solvent or support, or containing only in the state of insignificant trace. Such a dry extract thus contains only material derived from Silybum marianum (L.) Gaertn. It may also contain insignificant traces of extraction solvent.

By "organic solvent immiscible with oil obtained from achenes of Silybum marianum (L.) Gaertn. Is meant, within the meaning of the present invention, an organic solvent which is not capable of mixing, or only partially, with the oil obtained from achenes of Silybum marianum (L.) Gaertn., So that the mixture of the organic solvent and of the oil obtained from achenes of Silybum marianum (L.) Gaertn. gives a heterogeneous mixture in which at least two distinct phases can be observed.

By “fatty acid” is meant, within the meaning of the present invention, a carboxylic acid RI-CO2H whose chain RI is a linear or branched hydrocarbon chain, saturated or comprising C = C double bonds, the carboxylic acid comprising of 16 to 22 carbon atoms (including the carbon atom of the carboxylic acid function).

By “free” fatty acid (including linoleic acid) is meant, within the meaning of the present invention, a fatty acid not bound to other molecules (for example to glycerol or derivatives thereof to give glycerides or an alcohol to give a fatty ester). For the purposes of the present invention, the term “tocopherol” means Ga-tocopherol, β-tocopherol, β-tocopherol and d-tocopherol. For the purposes of the present invention, the term “C1 to C3 alcohol” is understood to mean an R2 — OH alcohol whose R2 chain is a saturated, linear or branched hydrocarbon chain comprising 1 to 3 carbon atoms. It may be methanol, ethanol, // - propanol or isopropanol, in particular methanol, ethanol or isopropanol. Preferably, it will be ethanol or isopropanol, in particular ethanol.

By "room temperature" is meant, within the meaning of the present invention, a temperature of 15 to 40 ° C, preferably 20 to 30 ° C, in particular of around 25 ° C. The term “hair and body hair” is understood to mean the hair, the body hair, the eyebrows, the eyelashes and / or the coat, preferably the hair.

The term “hair growth” is understood to mean the growth of the hair and / or the hairs as defined above, preferably the hair.

By "alopecia" is meant the total or partial loss of hair and / or body hair, for example linked to reduction in hair growth and / or acceleration of hair loss and / or body hair. This term includes but is not limited to androgenetic alopecia, postmenopausal alopecia, reactive alopecia, cicatricial alopecia, alopecia areata, and congenital alopecia. Preferably, it will be androgenetic alopecia, postmenopausal alopecia, reactive alopecia or alopecia areata. The consequences of alopecia are a temporary or permanent and partial or total absence of hair and / or body hair.

By “alopecia areata” is meant a massive loss of hair by patches, most often in the scalp. Affected people have a plaque without hair, most often round or oval in shape. However, the scalp is not affected and does not present any scars.

By “area of the scalp devoid of hair” is meant an area of the scalp, regardless of its size, which does not contain hair, or in which no longer grows enough hair to cover the area in question. It may be a patch of alopecia areata or partial or total alopecia. By “folliculitis” is meant an inflammation of one or more hair follicles, forming a papulo-pustule. It can therefore occur in all places with hair. Its origin can be bacterial, mycotic, viral or non-infectious. Folliculitis can be superficial, ostio-folliculitis, or deep. There are different scalp folliculitis, such as dissecting folliculitis or decalvating folliculitis. Scalp dissecting folliculitis is a chronic and rare suppurative dermatosis of the scalp. It manifests as numerous painful follicular and perifollicular inflammatory nodules, pustules and abscesses that interconnect via sinus tracts, ultimately resulting in scarring alopecia. Quinquaud's folliculitis is also an inflammatory cicatricial alopecia of the scalp, chronic and rare, occurring in middle-aged adults and characterized by the development of slowly extending and centrifugal alopecic plaques especially at the top and in the occipital area of the scalp. scalp, associated with perifollicular erythema, pustules and hemorrhagic crusts.

By the term "treating" alopecia we mean stopping alopecia, reducing alopecia and / or improving alopecia. Thus, "treating" alopecia includes limiting hair loss and / or body hair and / or promoting hair and / or body hair growth, increasing the density of hair follicles and / or regulating phases of the hair follicle cycle. .

By the term "preventing" alopecia, we mean reducing the risk of developing alopecia, or slowing the progression of alopecia in a mammal, preferably humans, which is susceptible to developing alopecia. The term “limit” is understood to mean slowing down, reducing, reducing and / or stopping.

By the term "promote" is meant to increase, increase, promote, enhance and / or accelerate.

In the present invention, the term “cosmetically or dermatologically acceptable” is intended to denote that which is useful in the preparation of a cosmetic or dermatological composition, which is generally safe, non-toxic and neither biologically nor otherwise undesirable and which is acceptable for a patient. cosmetic or dermatological use, in particular by topical application to the hair and / or scalp.

By “topical application” is meant an application to the skin, in particular to the scalp, mucous membranes, hair and / or body hair, in particular to hair and / or scalp. Extract according to invention

The extract according to the invention is an extract of achenes from Silybum marianum comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract.

According to a particular embodiment, the extract according to the invention contains at least 3% by weight, preferably at least 4% by weight of free linoleic acid relative to the weight of the dry extract. In particular, the extract according to the invention contains between 3% and 25% by weight, for example between 3 and 20% by weight, in particular 3% and 15% by weight, in particular between 4% and 10% by weight, in in particular between 4% and 6% by weight, for example approximately 5% by weight of free linoleic acid relative to the weight of the dry extract. The silymarin / free linoleic acid mass ratio of the extract according to the invention may in particular be less than 0.07, in particular less than 0.05 and in particular less than 0.01. The extract according to the invention may also comprise between 10% and 70%, in particular between 10% and 50%, more particularly between 10% and 30% by weight, in particular between 15% and 25% by weight of acids free fat compared to the weight of the dry extract.

According to a particular embodiment, the extract according to the invention contains at least 0.01% by weight, in particular at least 0.05% by weight of tocopherols relative to the weight of the dry extract. In particular, the extract according to the invention contains between 0.01% and 2% by weight, more particularly between 0.01% and 1% by weight, even more particularly between 0.01% and 0.5% by weight , in particular between 0.05% and 0.2% by weight, for example approximately 0.1% by weight of tocopherols relative to the weight of the dry extract. The silymarin / tocopherols mass ratio of the extract according to the invention may in particular be less than 1, in particular less than 0.1.

According to another particular embodiment, the extract according to the invention contains between 3% and 25% by weight, for example between 3 and 20% by weight, in particular between 3% and 15% by weight, in particular between 4% and 10% by weight, in particular between 4% and 6% by weight, for example approximately 5% by weight of free linoleic acid relative to the weight of the dry extract; and between 0.01% and 2% by weight, in particular between 0.01% and 1% by weight, even more particularly between 0.01% and 0.5% by weight, especially between 0.05% and 0.2% by weight, for example approximately 0.1% by weight of tocopherols relative to the weight of the dry extract. In particular, the silymarin / free linoleic acid mass ratio of the extract according to the invention may in particular be less than 0.07, in particular less than 0.01 and The silymarin / tocopherols mass ratio of the extract according to the invention may in particular be less than 1, in particular less than 0.1.

Preferably, the extract according to the present invention will be a dry extract.

According to a preferred embodiment, the extract according to the invention can be obtained by a process according to the invention described below.

Process for preparing the extract according to the invention

A process for preparing an extract according to the invention comprises in particular a step of extracting an oil obtained from achenes of Silybum marianum (L.) Gaertn. with an extraction solvent comprising, in particular consisting of, an aqueous hydrotropic solution, subcritical water or an organic solvent immiscible with oil obtained from achenes of Silybum marianum (L.) Gaertn. possibly mixed with water.

According to a particular embodiment, the extraction solvent comprises, in particular consists of, an organic solvent immiscible with oil obtained from achenes of Silybum marianum (L.) Gaertn. possibly mixed with water.

The oil-immiscible organic solvent derived from achenes of Silybum marianum (L.) Gaertn. may in particular be a C ₁ to C ₃ alcohol _.

The extraction solvent may in particular be a C 1 to C ₃ alcohol optionally mixed with water. The organic solvent immiscible with the oil obtained from achenes of Silybum marianum (L.) Gaertn., In particular a C 1 to C ₃ alcohol such as methanol, ethanol or isopropanol, in particular ethanol or isopropanol, preferably ethanol, can be used as a mixture with water, in particular in an organic solvent / water volume ratio of 70/30 to 100/0, in particular from 80/20 to 100/0, for example example about 80/20 or 90/10. The extraction solvent may in particular be chosen from methanol, a methanol / water mixture, ethanol, an ethanol / water mixture, isopropanol and an isopropanol / water mixture, in particular an ethanol / water mixture or an isopropanol / water mixture. water of preferably an ethanol / water mixture.

According to a particular embodiment, the extraction solvent will be methanol, an ethanol / water mixture in a volume ratio of approximately 80/20 or 90/10 or an isopropanol / water mixture in a volume ratio of approximately 90 / 10. The step of extracting achenes from Silybum marianum oil will be carried out in particular by mixing the oil obtained from achenes from Silybum marianum with the extraction solvent for 1 to 12 h and in particular at a temperature between 15 and 25 ° C, especially around 20 ° C. The amount of extraction solvent used to perform this extraction will advantageously be from 0.5 to 3 g, in particular from 1 to 3 g per 1 g of oil obtained from achenes of Silybum marianum (L.) Gaertn ..

An extraction phase and a lipid phase will then be obtained at the end of this extraction. The extraction phase will advantageously be separated from the lipid phase and recovered before being dried (in particular not evaporation of the extraction solvent), partially or completely, in particular under vacuum, to more or less remove the extraction solvent and obtain either the dry extract if the solvent is completely removed, or the concentrated extract which is diluted in residual solvent.

The oil obtained from achenes of Silybum marianum may advantageously be obtained by extraction from achenes of Silybum marianum (L.) Gaertn. (the achenes can be whole or in pieces), in particular by pressure, advantageously by cold pressing (that is to say without heating), at room temperature).

According to one embodiment according to the invention, the method according to the invention will comprise the following two successive steps:

(i) Extraction of an oil from achenes of Silybum marianum (L.) Gaertn., and

(ii) Extraction of oil from achenes of Silybum marianum (L.) Gaertn. with an extraction solvent, comprising, in particular consisting of, an aqueous hydrotropic solution, subcritical water or an organic solvent immiscible with oil obtained from achenes of Silybum marianum (L.) Gaertn. possibly mixed with water.

According to a preferred embodiment according to the invention, the method according to the invention will comprise the following successive steps:

(i) Optionally, extraction of an oil from achenes of Silybum marianum (L.) Gaertn., (ii) Extraction of the oil obtained from achenes of Silybum marianum (L.) Gaertn with an extraction solvent, comprising, in particular consisting of a hydrotropic aqueous solution, subcritical water or an organic solvent immiscible with the water. oil obtained from achenes of Silybum marianum (L.) Gaertn. possibly mixed with water,

(iii) Recovery of the extraction phase obtained in step (ii), and

(iv) Partial or total drying of the extraction phase to give a concentrated or dry extract according to the invention.

Step (i) will advantageously be carried out by cold pressing the achenes of Silybum marianum (L.) Gaertn., Whole or in pieces.

Step (ii) will advantageously be carried out with an extraction solvent as defined above, and in particular chosen from methanol, a methanol / water mixture, ethanol, an ethanol / water mixture, isopropanol, and a mixture isopropanol / water.

The extraction solvent may in particular be an organic solvent immiscible with the oil obtained from achenes of Silybum marianum (L.) Gaertn, in particular a C1 to C3 alcohol such as methanol, ethanol or alcohol. 'isopropanol, optionally mixed with water, in particular in an organic solvent / water volume ratio of between 80/20 and 100/0, in particular between 85/15 and 95/5, in particular of approximately 90/10 . A preferred extraction solvent is an isopropanol / water mixture in a volume ratio of about 90/10.

The extraction step (ii) can be carried out by mixing the oil obtained from achenes of Silybum marianum with the extraction solvent for 1 to 12 h and in particular at a temperature of 15 to 25 ° C, in particular approximately 20 ° C. The amount of extraction solvent used to perform this extraction will advantageously be from 0.5 to 3 g, in particular from 1 to 3 g per 1 g of oil obtained from achenes of Silybum marianum (L.) Gaertn ..

This extraction step (ii) makes it possible to obtain at the end an extraction phase of interest and a lipid phase.

Step (iii) will advantageously be carried out by separating the extraction phase from the lipid phase. Step (iv) will advantageously be carried out under vacuum. Cosmetic and dermatological applications

According to a first aspect, the present invention relates to an extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention for its use for promoting hair growth.

The invention also relates to an extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention for its use in the treatment or prevention of alopecia such as Androgenetic alopecia, reactive alopecia, postmenopausal alopecia or areata alopecia, or to treat dissecting folliculitis.

Achenes extract from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention can be used in support of a hair transplant, in particular during micro- transplantation of follicular units. A follicular unit is a group of hairs, naturally joined together in the scalp in small bundles, which can contain one to four hairs. The use of an extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention is perfectly suitable, in particular as an accompaniment to a laser hair transplant.

Achenes extract from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention can also be used in conjunction with a treatment based on plasma rich in platelets (PRP). It is a concentrate of platelets, and therefore rich in growth factors, which is injected into the scalp.

Achenes extract from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention can also be used in conjunction with hair mesotherapy. This is a technique commonly used in the medical and aesthetic world, which consists of injecting different polyvitamins into the dermis of the scalp to nourish the hair follicle in depth, which makes it possible to treat the hair while improving blood circulation to the scalp. Usually two months of treatment are enough to normalize the hair loss and sometimes increase the hair density. Achenes extract from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention can thus be used before or concomitantly with a hair transplant or with a medical treatment scalp such as treatment with platelet rich plasma or hair mesotherapy.

According to a second aspect, the present invention relates to a dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention, with at least one dermatologically or cosmetically acceptable excipient for its use to promote growth capillary. The invention also relates to a dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention, with at least one dermatologically or cosmetically acceptable excipient for its use in the treatment or the prevention of alopecia such as androgenetic alopecia, reactive alopecia, post-menopausal alopecia or alopecia areata, or else to treat dissecting folliculitis.

The dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention, with at least one dermatologically or cosmetically acceptable excipient can be used as an accompaniment to a hair transplant, including a laser hair transplant.

The dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention, with at least one dermatologically or cosmetically acceptable excipient can also be used as an accompaniment to treatment with platelet rich plasma (PRP).

The dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention, with at least one dermatologically or cosmetically acceptable excipient can also be used as an accompaniment to 'capillary mesotherapy.

The dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract according to the invention, with at least one dermatologically or cosmetically acceptable excipient can thus be used beforehand or concomitantly hair transplant or scalp medical treatment such as platelet rich plasma treatment or hair mesotherapy. Advantageously, the extract included in the dermatological or cosmetic composition is as described above.

According to a third aspect, the present invention relates to a method of dermatological treatment of an area of the scalp devoid of hair, comprising the topical application to the area of the scalp devoid of hair of an extract of achenes from Silybum marianum ( L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract or of a dermatological composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, with at least one dermatologically acceptable excipient, prior to or concomitantly with a hair transplant or with a treatment scalp medical treatment such as treatment with platelet rich plasma or hair mesotherapy.

Preferably, this method of dermatological treatment according to the invention precedes a hair transplant, in particular a laser transplant.

According to a particular embodiment of the invention, the dermatological treatment method according to the invention is carried out for 1 to 6 weeks, preferably 1 to 4 weeks and more preferably 2 to 4 weeks before a hair transplant or a medical treatment of the scalp such as a treatment with a plasma rich in platelets or a hair mesotherapy. The invention is preferably aimed at an extract and a cosmetic or dermatological composition according to the invention which is provided in its own form and suitable for topical application, in particular to the scalp and / or the hair.

The cosmetic or dermatological composition according to the invention can thus be provided in the forms which are usually known for topical administration, that is to say in particular lotions, shampoos, balms, foams, gels, dispersions. , emulsions, sprays, serums, masks or creams, with excipients allowing in particular penetration in order to improve the properties and accessibility of the active principle.

Advantageously, the composition according to the invention can be provided in the forms which are usually known for topical administration to the hair and the scalp, that is to say in particular a shampoo, a conditioner, a hair cream, a hair lotion, a mask or a spray, in particular without rinsing.

A distinction is thus made between formulated products which can be rinsed and formulated products which do not require rinsing. Preferably, the composition according to the invention has a light texture further allowing optimum penetration without greasing the hair and / or the body hair, or the scalp.

These compositions generally contain, in addition to the extract according to the present invention, a physiologically acceptable medium, generally based on water or on a solvent, for example alcohols, ethers or glycols. They can also contain surfactants, complexing agents, preservatives, stabilizers, emulsifiers, thickeners, gelling agents, humectants, emollients, trace elements, essential oils, perfumes, colorants, moisturizers, etc. According to a particular embodiment, the composition according to the invention comprises, as a cosmetically or dermatologically acceptable excipient, isopropanol, polyethylene glycol (PEG) or a mixture of these. Thus, advantageously, the composition according to the present invention will comprise, in particular will consist of, an extract according to the invention, isopropanol and PEG. The isopropanol / PEG mass ratio will advantageously be between 1/2 and 2/1, in particular between 1 / 1.5 and 1.5 / 1, in particular will be approximately 1/1. The PEG may in particular have a number-average molecular mass of between 200 and 600 g / mol, in particular between 200 and 500 g / mol, in particular between 200 and 400 g / mol, for example between 250 and 350 g / mol, in particular about 300 g / mol. It may thus be in particular PEG 300. In another particular embodiment of the invention, the composition according to the invention is characterized in that it is provided in a form suitable for oral administration.

The composition according to the invention may then be in the forms which are usually known for oral administration, that is to say in particular tablets, gelatin capsules, powders, granules and oral solutions or suspensions. When preparing a solid composition in the form of tablets, the main active ingredient can be mixed with a cosmetic or dermatological vehicle such as gelatin, starch, lactose, magnesium stearate, talc, gum arabic. , silica or the like. The tablets can be coated with sucrose or other suitable materials or they can be treated so that they have a prolonged or delayed activity and that they continuously release a predetermined amount of active. A capsule preparation can be obtained by mixing the active ingredient with a diluent and pouring the resulting mixture into soft or hard capsules. Advantageously, the composition according to the present invention comprises 0.01 to 15% by weight, preferably 0.1 to 10% by weight, of an extract according to the invention relative to the total volume of the composition. EXAMPLES

Example 1: preparation of extracts

Process according to the invention giving an isopropanolic extract 90 (extract I) comprising a low content of silymarin.

Cold pressing of achenes from Silybum marianum to obtain an oil from achenes from Silybum marianum,

Extraction of the oil obtained from achenes of Silybum marianum with an isopropanol / water mixture (90/10 v / v) with 1 gram of the isopropanol / water mixture per gram of oil for 2 hours at 20 ° C,

Recovery of the isopropanolic phase, and Evaporation of the solvent.

Methanolic (extract M) and ethanolic (extract E) extracts were obtained in a similar manner by replacing the isopropanol / water mixture (90/10 v / v) respectively with methanol and an ethanol / water mixture (90/10 v / v). The oil obtained from achenes of Silybum marianum is extracted respectively with 3 volumes of methanol and 3 volumes of the ethanol / water mixture (90/10 v / v) for 1 volume of oil for 2 hours at 20 ° C.

These various extracts were characterized by UPLC (ultra high performance liquid chromatography) or by GC-MC (gas chromatography coupled to mass spectrometry) according to the protocols detailed below.

Evaluation protocol of the extracts obtained

Protocol 1: evaluation of the silymarin content by UPLC

Preparation of sample and control:

Silymarin control: prepare a 5 mg solution of silymarin in 10 ml of a methanol / water (60:40) (v / v) mixture.

Sample: heat the dry extract to be analyzed (extract M, E or I) at 35 ° C with stirring until a homogeneous and clear solution is obtained. Weigh exactly 200 mg of the extract, dissolve it in 10 ml of a methanol / dichloromethane mixture allowing total solubilization of the extract and homogenize the solution. This mixture ranges from the methanol / dichloromethane (1: 1) v / v) ratio to pure methanol. Analytical conditions:

Column: Acquity BEH Shield Cl 8 150mm x 2.1mm - l, 7pm (Waters) Mobile phase:

A: water + 0.1% formic acid - B: Acetonitrile + 0.1% formic acid

Gradient according to Table 1 below:

[Table 1]

Column temperature: 40 ° C Flow rate: 0.4 ml / min Detection: 287 nm Injection volume: 1 pL.

Protocol 2: Evaluation of the linoleic acid content by UPLC Preparation of the sample and the control:

Control Linoleic acid: prepare a 10 mg solution of linoleic acid in 10 ml of a methanol / dichloromethane (1: 1) (v / v) mixture.

Sample: heat the dry extract to be analyzed (extract M, E or I) at 35 ° C with stirring until a homogeneous and clear solution is obtained. Weigh exactly 50 mg of the extract, dissolve it in 1 ml of a methanol / dichloromethane mixture allowing total solubilization of the extract and homogenize the solution. This mixture ranges from the methanol / dichloromethane (1: 1) (v / v) ratio to pure methanol. Analytical conditions:

Column: Acquity BEH Shield Cl 8 150mm x 2.1mm - 1.7pm (Waters) Mobile phase: A: water + 0.1% formic acid B: Acetonitrile + 0.1% formic acid Gradient according to Table 2 below:

[Table 2]

Column temperature: 40 ° C Flow rate: 0.4 ml / min Detection: 215 nm

Injection volume: 1 pL.

Protocol 3: Evaluation of the fatty acid content by GC-MS Preparation of the sample: Heat the dry extract to be analyzed at 35 ° C while stirring until a clear homogeneous liquid is obtained.

Solubilize 20 mg of the extract in 800 mΐ of a methanol / dichloromethane mixture (1: 1) (v / v).

Add 200 mΐ of the derivatizer N, 0-Bis (trismethylsilyl) trifluoroacetamide (BSTFA) + Trimethylchlorosilane (TMCS) (99: 1) (Supelco-Sigma Alrich).

Vortex for 1 minute.

Gas Chromatography (GC) Conditions:

Column: DB-5ms (Agilent Technologies); 30m x 0.25mm; 0.25 pm Injection: T = 300 ° C; Mode = Split; Split ratio = 100: 1 Furnace: temperature gradient (° C)

Initial temperature = 150 ° C

Gradient = 7 ° C / min until final temperature = 340 ° C Maintain at 340 ° C for 10 minutes Carrier gas flow rate: 1 ml / min

Detection: MS-EI, T = 300 ° C, Scan time = 0.2 sec; Full Scan Start Mass = 40; Full Scan End Mass = 600.

Injection volume: lpL Results

Achenes extract I of Silybum marianum according to the invention poor in silymarin predominantly contains substances having a retention time of between 13 and 30 minutes by UPLC. The silymarin content of extracts I was determined by LIPLC after calibration with control solutions of commercial silymarin (Sigma Aldrich).

Extract I contains 0.06% by mass of silymarin.

The contents of free fatty acids and more particularly of linoleic acid in extract I were determined by UPLC and by GPC and are presented in Table 3 below.

[Table 3]

The inventors were able to demonstrate that the UPLC and CPG profiles of the 3 extracts of achenes according to the invention obtained by methanolic (extract M), ethanolic 90 (extract E) and isopropanolic 90 (extract I) extraction are similar.

The various analyzes carried out by UPLC and GC-MS made it possible to highlight the following characteristics: The isopropanolic extract 90 of achenes according to the invention (extract I) contains virtually no silymarin, particularly polar flavonolignans.

The UPLC and CPG profiles of the 3 extracts of achenes according to the invention obtained by methanolic, ethanolic 90 and isopropanolic 90 extraction are very similar.

Example 2: Quantification of the Keratin 75 protein in the forehead follicles of human subjects

The purpose of this example is to evaluate the effects of an extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2% by weight of silymarin on the expression of the protein Keratin 75 in humans. Indeed, such pharmacological activity is of interest in the field of treatment and / or prevention of hair loss, in particular by promoting their growth.

Methods A topical preparation of extract I prepared in Example 1 was formulated at 1.75% or 7.0% (w / v) of the dry extract, in an isopropanol / PEG 300 (1: 1) mixture. ) (w / w), then put in a spray for application twice a day for the duration of treatment.

13 healthy volunteers were followed for 4 to 12 weeks depending on their availability. This study was carried out in accordance with the Declaration of Helsinki, with the written consent of each subject. This is a longitudinal observational single-center study. The subjects were followed in a private practice with close supervision by the same staff throughout the study, supplemented by permanent digital contacts and exchanges with the subjects. Weekly monitoring based on digital installations has been installed. A follicle sample was taken at each visit. Cyanoacrylate follicle samples were taken from the forehead in subjects according to Piérard et Coll (Scientific World Journal, 2014 ID 463634, 2014) using a drop of 2-ethyl cyanoacrylate adhering to a glass microscope slide. .

Protein extraction:

The biopsies are detached from the glass slide in distilled water for 30 minutes at room temperature, are cut into small parts and then homogenized in a 2 mM Tris-HCl extraction buffer, pH 6.8, 3% SDS, lOmM sodium pyrophosphate, 5mM EDTA, and 2mM sodium vanadate. The samples are heated to 50 ° C for

3 hours. The extracts are centrifuged at 10,000 revolutions / min for 10 minutes. The determination of the proteins in the supernatants is carried out by the method according to Bradford (Anal Biochem 72: 248-254, 1976) using the Bio-Rad reagent (Cressier, Switzerland). The sebocyte cultures are washed with PB S buffer then the cells are lysed in a specific buffer (50 mM Tris-HCl pH 7.4, 150 mM NaCl, ImM EDTA, 1% Triton ™ X-100). The suspensions are passed through a sonicator and then analyzed by the Bradford method.

Protein samples are analyzed by Western Blot using a standard procedure and the following antibody: polyclonal rabbit anti-human IgG K75, dilution 1: 5000 (Fisher Scientific, Reinach, Switzerland).

Proteomic analysis was performed by electrophoresis (SDS-PAGE), followed by Coomassie staining. The colored protein bands are harvested and analyzed on the University of Geneva's proteomics platform.

Results

The level of expression of the K75 protein (densitometric unit of western blot bands) in the hair follicles of the forehead of human subjects is shown in the table

4 below before and after the treatment with an extract according to the invention. [Table 4]

The inventors clearly demonstrate that the treatment with an extract according to the invention induces a statistically significant increase (p <0.001) in the expression of the K75 protein. It is interesting to note that this increase is observed in all patients regardless of the concentration tested or the duration of treatment carried out. Indeed, after 4 weeks of treatment, the increase in the expression of the K75 protein already seems very marked.

Example 3: quantification of the Keratin 75 protein in the scalp of a patient with alopecia areata

In this severe hair disorder, it is observed that the expression of K75 is extremely low. The patient is treated with the same extract at a concentration of 7%, and in the same way as in Example 2. The results obtained, namely the level of expression of the K75 protein (densitometric unit of the bands of western blots ) in the hair follicles of the patient suffering from alopecia areata, before and after treatment with an extract according to the invention, are presented in Table 5 below. [Table 5]

The inventors thus demonstrate that a treatment comprising an extract according to the invention makes it possible to significantly increase the level of expression of K75 in a patient suffering from alopecia areata. It is interesting to note that at the end of the treatment, a regrowth capillary could be observed.

All of these results allow the inventors to demonstrate the value of an extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2% by weight of silymarin in promoting hair regrowth.

Example 4: quantification of the Keratin 75 protein at the level of the scalp on patches of alopecia areata and hair regrowth

In this severe hair disorder, it is observed that the expression of K75 is extremely low. Two patients with alopecia areata are treated with the same extract at a concentration of 7% for 4 weeks and in the same way as in Example 2, on two or three patches of alopecia areata. The results (5 patches of alopecia areata in total) of K75 protein density and hair density are shown in Table 6 below. [Table 6] The inventors thus demonstrate that a treatment comprising an extract according to the invention makes it possible to significantly increase the level of expression of keratin 75 in two patients suffering from alopecia areata. This increase is linked to hair regrowth. Indeed, the hair density has more than doubled after application of the extract according to the invention. The local application of an extract according to the invention to the scalp therefore made it possible to create conditions favorable to hair regrowth. The inventors therefore put clearly evident that such an extract would be useful to apply in prevention of a hair transplant or a medical treatment such as PRP or mesotherapy.

Example 5: specific effect of an extract of achenes from Silybum marianum on the phosphorylation of EGFR and PDGFRB receptors in cells of the dermal papilla

The objective of this study is to show that an extract of achenes of Silybum marianum tested at 30 pg / mL specifically induces the tyrosine phosphorylation of receptors with tyrosine kinase (phospho-RTK) activity and of kinases of different pathways. signaling (phospho-kinases) unlike Silymarin (Sigma) tested at 0.06 pg / mL. The control was treated with dimethylsulfoxide (DMSO), used as a solvent for Silybum marianum extract and Silymarin.

The study was performed on dermal papilla cells isolated from human hair follicles and cultured in a Petri dish for 48 hours. The dermal papilla cells were then stimulated for 1 hour in the presence of the extract of Silybum marianum or Silymarin. Finally, total cell lysates were prepared and tested for the phosphorylation of various biological targets. The mapping of these targets was obtained using two “antibody arrays” kits which use a cellulose membrane on which antibodies are printed to detect the presence of proteins of interest (Proteome profiler human array kit, R&D Systems) . The list of pharmacological targets screened in these tests is as follows and available online:

• 49 phosphoreceptors with tyrosine kinase activity

(https://www.mdsystems.com/products/proteome-profiler-human-phospho-rtk-array- kit_ary001b)

• 43 signaling phospho-kinases (https://www.mdsystems.com/products/proteome-profiler-human phospho-kinase-array- kit_ary003b # product-datasheets).

The chemiluminescence signals were finally detected using a densitometer (ChemiDoc, Biorad) and quantified with the Image J 1.52 software using the Microarray profile plugin. Analysis of the data made it possible to determine the average pixel intensity for each experimental condition and to measure a ratio relative to the DMSO control. The tests were finally carried out on 2 independent donors of dermal papilla cells and carried out in duplicate. The results of the phosphoreceptors are shown in Table 7 below. [Table 7]

These results demonstrate that the extract of Silybum marianum markedly increases the tyrosine phosphorylation of these two receptors by a ratio of 1.91 and 2.77 respectively in response to one hour of treatment. On the other hand, the ratio remains close to 1, 1.02 and 0.76 for EGFR and PDGFR respectively, following incubation with silymarin. These data therefore show that the achenes extract of Silybum marianum at 30 pg / ml has EGFR and PDGFR as specific targets and that the phosphorylation of these 2 receptors is not modulated by silymarin at a concentration of 0, 06 pg / ml. In addition, the results of the screening for signaling phospho-kinases are presented in Table 8 below which shows the induction of tyrosine phosphorylation of signaling kinases by the extract of achenes from Silybum marianum, the values being the ratios of Silybum mariannum extract / Control. [Table 8]

These experimental results make it possible to confirm that the PDGFR is indeed tyrosinated on the Y751 residue in response to the extract of Silybum mariannum (ratio 1.94). Furthermore, this extract activates the signaling pathways known for EGFR and PDGFR, namely: ERK 1/2 (T202 / Y204, T185 / Y187); GSK3 a / b (S21 / S9); Akt 1/2/3 (S473); STAT 5a (Y694); STAT 5a / b (Y694 / Y699) and total b-catenin.

In conclusion, all the results of this example show that the extract of achenes from Silybum mariannum activates specifically and independently of the presence of Silymarin the phosphorylation of the tyrosine of EGFR and PDGFR, as well as their signaling pathways. in the cells of the dermal papilla.

Claims

1. Achenes extract from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin based on the weight of the dry extract for its dermatological use to promote hair growth.

2. Achenes extract from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract for its use according to claim 1, characterized in that said extract is in a form suitable for a topical application.

3. Achenes extract from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract for its use according to any one of claims 1 and 2, characterized in that said extract allows prevent or treat alopecia.

4. Achenes extract from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract for its use according to Claim 3, characterized in that the alopecia is chosen from the group consisting by androgenetic alopecia, reactive alopecia, postmenopausal alopecia, alopecia areata, and cicatricial alopecia, in particular folliculitis and preferentially dissecting folliculitis.

5. Achenes extract from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract for its use according to any one of claims 1 to 4, characterized in that said extract is used before or concomitantly with a hair transplant or a medical treatment of the scalp such as a treatment with a plasma rich in platelets or a hair mesotherapy.

6. Dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, with at least one dermatologically or cosmetically acceptable excipient for its dermatological use to promote hair growth.

7. Dermatological or cosmetic composition for its use according to claim.

6, characterized in that it is in a form suitable for topical application.

8. Dermatological or cosmetic composition for its use according to any one of claims 6 and 7, characterized in that the composition comprises 0.01% to 15% by weight, extract of achenes from Silybum marianum (L. ) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, relative to the total weight of the composition.

9. Dermatological or cosmetic composition for its use according to any one of claims 6 to 8, characterized in that the composition makes it possible to prevent or treat alopecia.

10. Dermatological or cosmetic composition for its use according to claim 9, characterized in that the alopecia is chosen from the group consisting of androgenetic alopecia, reactive alopecia, post-menopausal alopecia, alopecia areata, and cicatricial alopecia, in particular folliculitis and preferably dissecting folliculitis.

11. Dermatological or cosmetic composition for its use according to any one of claims 6 to 10, characterized in that said composition is used before or concomitantly with a hair transplant or with a medical treatment of the scalp such as treatment with platelet-rich plasma or hair mesotherapy.

12. Cosmetic use of an extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, or of a dermatological or cosmetic composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, with at least one dermatologically or cosmetically acceptable excipient, to promote hair growth.

13. Use according to claim 12, characterized in that said extract or said composition is in a form suitable for topical application.

14. Use according to claim 12 or 13, characterized in that said composition comprises 0.01% to 15% by weight of extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, relative to the total weight of the composition

15. A method of dermatologically treating a hairless area of the scalp, comprising topically applying to the hairless area of the scalp an achenes extract from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract or of a dermatological composition comprising at least one extract of achenes from Silybum marianum (L.) Gaertn. comprising less than 0.2%, preferably less than 0.1% by weight of silymarin relative to the weight of the dry extract, with at least one dermatologically acceptable excipient, prior to or concomitantly with a hair transplant or with a treatment scalp medical treatment such as treatment with platelet rich plasma or hair mesotherapy.