FR3136654A1 - PHEOPHYCEA EXTRACTS FOR THE MAINTENANCE OR TREATMENT OF OILY AND/OR ACNE PRONE SKIN - Google Patents

Abstract

PHEOPHYCIA EXTRACTS FOR THE MAINTENANCE OR TREATMENT OF OILY AND/OR ACNE PRONE SKIN The present invention relates to the field of cosmetics and dermatology, and more particularly that of skin disorders linked to oily and/or acne prone skin. acneic. For this purpose, the invention relates to an aqueous extract derived from at least one plant of the Pheophyceae class, in particular derived from Sargassum muticum, for its use in the maintenance or treatment of oily or acne-prone skin, in particularly in the maintenance or improvement of skin texture, the maintenance and maintenance of the microbiota, the prevention or treatment of acne, including in particular the reduction of the C. acnes biofilm, the reduction of the size and number of pores, prevention or treatment of inflammatory reactions, protection against oxidative stress due to environmental factors such as UV and air pollution, or stress due to skin irritants such as SLS.

Description

PHEOPHYCEA EXTRACTS FOR THE MAINTENANCE OR TREATMENT OF OILY AND/OR ACNE PRONE SKIN FIELD OF INVENTION

The present invention relates to the field of cosmetics and dermatology, and more particularly that of skin disorders linked to oily and/or acne-prone skin.

More specifically, the invention relates to the use of an aqueous extract derived from at least one plant of the Pheophyceae class for improving the quality of skin with imperfections presenting in particular dilated and visible pores, as well as inflammation. , and for the protection of the skin against the deleterious effects due to environmental factors, or pollutants, contributing to such imperfections.

STATE OF THE ART

The skin, the interface between our body and our environment, is colonized by billions of microorganisms, including bacteria, fungi, yeasts, viruses, grouped under the term skin microbiota. The microbiome refers to the specific environment in which a microbiota evolves. The skin microbiome thus brings together all the microorganisms present both on the surface of the skin and also in the skin appendages, including the pilosebaceous units and the sweat glands.

Characterized by significant bacterial diversity, and by inter- and intra-individual variability (from one individual to another and from one anatomical area to another: sebaceous, wet or dry areas), the skin microbiota is essential to maintain skin homeostasis. It is involved in strengthening the barrier function, in the education of the immune system, the establishment of the immunological barrier, and in the control of bacteria that can become potentially pathogenic. Certain resident microorganisms, including Staphylococcus epidermidis and Cutibacterium acnes ( C.acnes ), strongly represented in the skin microbiome, participate in antibacterial defenses via the production of peptides or other anti-microbial compounds and the regulation of the pH of the stratum corneum.

The alteration of the microbiota or dysbiosis is observed in multiple skin disorders, including acne, psoriasis, atopic dermatitis, rosacea, dandruff, etc. The disruption of this ecosystem, generally characterized by a reduction in bacterial diversity , promotes the pathogenicity of certain microorganisms and the development of infection. Pollution, overproduction of sebum observed during puberty or in cases of hormonal disorders in adults, prolonged wearing of masks, are among the factors that can influence the skin microbiota and disrupt its natural balance (Krutmann J. et al , 2017).

Acne vulgaris can appear during adolescence. It affects 95% of boys and 83% of girls at the age of 16. It also affects the adult population, not just adolescents. Urban populations are more affected than rural populations and bear witness to the impact of pollution on their development. Around 20% of affected people develop severe acne, which results in scarring. In addition to pollution, hormonal disorders, psychological stress is also an important aggravating factor in acne.

Sebaceous zones are particularly rich in pilosebaceous units. These cutaneous appendages are composed of a sebaceous gland associated with a hair follicle articulated between the dermis and the epidermis. They help maintain the barrier function of the skin while fighting against external bacterial and fungal attacks, in particular through the production and secretion of sebum. They are largely colonized by C. acnes , a bacillus-shaped bacteria, Gram positive, anaerobic, aerotolerant, lipophilic. It can represent up to 87% of the microorganisms present in fatty areas.

C. acnes , or Cutibacterium acnes , historically described as the "acne bacillus" and formerly Propionibacterium acnes , is one of the crucial players widely associated with the development of skin imperfections as observed in acne (Scholz, CFP and al, 2017; Fitz-Gibbon S et al, 2013). However, more recent studies demonstrate not only the existence of six major phylotypes (IA1, IA2, IB, IC, II and III), but also a loss of their diversity in patients with severe acne, in favor of the phylotype IA1. Studies show that it is not just the proliferation of C. acnes alone that triggers acne, but the variation of two components: the loss of diversity of the skin microbiome and the selection of certain phylotypes of C. acnes including the IA1 phylotype (Rozas et al., 2021; Dagnelie et al., 2019). C. acnes of phylotype IA1 also produces a surface and adhesion protein (DsA1), which the other phylotypes II and III do not produce and gives it the ability to adhere to keratinocytes, a step upstream of the formation of micro -colonies and biofilms of C. acnes (Spittaels KJ et al, 2020).

C. acnes mainly resides deep, at the level of the pilosebaceous units, due to a low oxygen concentration and the presence of nutrients from sebum appreciated by the bacteria. Sebum is in fact composed of lipid elements (glycerides, squalene), fatty acid (sapienic acid) and waxes (cerides) to moisturize and soften the skin as well as providing antioxidant components. Sebum is an essential protective substance for the skin, regulated by the action of hormones and growth factors, such as IGF-1 (Insulin-Like Growth Factor-1).

The alteration of sebum, qualitatively and quantitatively, respectively hyperseborrhea and dysseborrhea, modifies the microbiome with a loss of diversity and a selection of certain phylotypes. In addition, it is accompanied by the appearance of lipid fractions, including peroxidized squalene, with pro-inflammatory properties. Environmental factors, such as UV rays or atmospheric pollutants, induce this peroxidation of squalene, in this case potentiating the inflammatory state (Pham DM et al, 2015). Finally, the alteration of sebum also disrupts the epidermal differentiation process, contributing to hyperkeratinization and obstruction of the hair infundibulum or pore of the hair follicle, responsible for the appearance of dilated pores, whiteheads or spots. comedones often precursors of inflammatory lesions. The black appearance of comedones is due to the oxidation of sebum which can be accentuated by environmental factors, such as pollution (Mitoma C. et al, 2015)

C. acnes has a direct action on the sebaceous glands by allowing on the one hand the maintenance of hyperseborrhea, and on the other hand by disrupting the differentiation process of the keratinocytes responsible for the phenomenon of hyperkeratinization. (Choi et al., 2018). These disorders are characterized by a thickening of the epidermis, due to the excessive proliferation of keratinocytes which line the excretory channel of the pilosebaceous unit, at the level of the skin pores. This generates favorable conditions conducive to colonization by C. acnes , setting up a real vicious circle marked by the accumulation of keratins and sebum generating the dilation of pores. These then become more visible, including the appearance of comedones or whiteheads (Gollnick et al 2015; Conwill et al., 2022). In the event of rupture of the comedones, associated with the presence of the IA1 phylotype of C. acnes , inflammatory lesions (papules, pustules, nodules or cysts) appear. The bacteria secretes virulent molecules with pro-inflammatory and cytotoxic properties, inducing the degradation of host tissues and inflammation, including lipases, proteases, hyluronate lyase and CAMP factors (Christie–Atkins–Munch -Petersen). These factors have the capacity to stimulate Toll-Like Receptors or TLRs, present on the surface of keratinocytes, sebocytes and immune cells. The stimulation of TLRs, by their specific ligands from C. acnes , results in a signaling cascade. This leads to the activation of nuclear factor kappa B (NFκB) and the induction of an immune response via the modulation of the transcription of certain target genes encoding pro-inflammatory chemokines and cytokines (IL-1α, IL-1β, IL-8, IL-6, IL-10, IL-17, IL-12, TNF-α, etc.) as well as anti-microbial peptides, human defensin 2 (HBD2) type (Groves et al., 1995; Feldmeyer et al., 2010, Kumar, 2021).

Additionally, C. acnes secretes extracellular polymeric substances (EPS) which give it the ability to generate biofilms. These adhesive structures form a strong and protective barrier allowing a large number of bacteria to survive unfavorable conditions. Bacterial biofilms constitute important reservoirs for bacteria and according to Richards JJ et al. 2009, it is estimated that 80% of our planet's microbial biomass resides in the form of biofilm. In addition to the virulence factors described earlier, biofilms are responsible for the pathogenicity of the bacteria by allowing it, among other things, to resist the host's immune response and antibiotics rendering treatments ineffective.

Faced with this resistance problem, there is therefore an urgent need to find solutions which consist of acting upstream of the infection, in particular to maintain the balance of the microbiota and limit the formation of pathogenic C. acnes biofilms.

Furthermore, and as mentioned previously, exposure of the skin to atmospheric pollution, UV rays or irritating agents are among the factors aggravating the condition of oily and/or acne-prone skin.

Pollution is a disruptive factor in the skin microbiome which weakens it and promotes dysbiosis associated with the development of skin disorders including imperfections observed in acne-prone skin (Krutmann J. et al, 2017, Araviiskaia E, et al, 2019) .

In recent years, a growing number of studies have demonstrated a link between skin problems and exposure to atmospheric pollutants, such as fine suspended particles, volatile organic compounds (VOCs), oxides, ozone (O3), polycyclic aromatic hydrocarbons or even cigarette smoke. These pollutants generate a state of oxidative stress, due to the production and accumulation of free radicals and other highly reactive molecules grouped under the term reactive oxygen species. The state of oxidative stress also occurs when endogenous antioxidant defenses become insufficient, exhausted by repeated exposure to environmental stress.

In this state of oxidative stress, the various cellular compounds (lipids, proteins, DNA) are oxidized, causing a loss of their functionality as well as that of the cells leading to a loss of homeostasis and skin integrity. The weakening of the barrier function then promotes the penetration of certain polluting agents or other exogenous molecules (including bacterial compounds), which leads to an inflammatory state. The latter leads to the development or potentiates certain skin disorders already present. In addition, if the inflammation is not stopped, it becomes chronic or so-called low grade because it is silent. On the skin, it causes the appearance of early signs of aging but also pigmentation disorders such as post-inflammatory hyperpigmentation spots, responsible for the loss of homogeneity of the complexion.

Irritant agents often present in many cosmetic products, such as sodium dodecyl sulfate (SLS), a sulfated surfactant with powerful detergent action, also disrupt the skin microbiome in addition to altering barrier function (Leoty-Okombi S . et al, 2021). Dysbiosis associated with a loss of diversity and the selection of certain potentially pathogenic bacteria (phylotype IA1 of C. acnes ) can effectively cause the stimulation of Toll-Like Receptors like TLR4 and the activation of the NFkB signaling pathway involved in low-grade inflammation (Song C et al, 2021).

The present invention aims to respond to all of the problems mentioned above.

OBJECTS OF THE INVENTION

Thus, a first object of the invention is to propose a solution for the maintenance, care and treatment of oily and/or acne-prone skin, in particular a solution for maintaining and maintaining the balance of the microbiota, limiting the formation of C. acnes biofilms in order to prevent its virulence and pathogenicity and their consequences on the skin, including the triggering of a skin inflammatory response, and to improve the quality and texture of the skin by limiting obstruction and the dilation of pores responsible for the grainy appearance of the skin.

Another object of the present invention is to propose a solution which also makes it possible to limit the deleterious and aggravating effects of pollution, or irritating agents, in oily and/or acne-prone skin, in order to preserve the homeostasis and integrity of the skin for a reinforced skin barrier and refinement of the skin texture.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is based on the unexpected discovery that an aqueous extract of Pheophyceae, in particular Sargassum muticum , has notable effects on the skin with very interesting cosmetic and dermatological properties for restoring the condition of skin prone to oiliness and/or oiliness. or acneic.

Thus, the invention relates to an aqueous extract derived from at least one plant of the Pheophyceae class for its use in the maintenance or treatment of oily or acne-prone skin.

In particular according to the invention, the maintenance or treatment of oily or acne-prone skin includes the maintenance or improvement of the texture of the skin, the maintenance and maintenance of the microbiota, the prevention or treatment of acne, including in particular the reduction of C. acnes biofilm, reduction in the size and number of pores, prevention or treatment of inflammatory reactions, protection against oxidative stress due to environmental factors such as UV and air pollution, or stress from skin irritants such as sodium dodecyl sulfate.

In particular according to the invention, the maintenance or treatment of oily or acne-prone skin includes the inhibition of interleukin-1α and/or the inhibition of lipid peroxidation and/or the inhibition of reactive species. to oxygen (ROS).

By “acne-prone skin” within the meaning of the invention is meant skin exhibiting acne. “Acne-prone skin” or “acne-prone skin” means the same type of skin within the meaning of the invention.

By “skin with a tendency to be oily” within the meaning of the invention, we mean skin exhibiting excessive secretion of sebum.

By “aqueous extract” according to the invention, we understand that the polar (hydrophilic) compounds have become solubilized and/or have been extracted in a polar solvent.

Thus, according to the invention, the extract comes from at least one plant of the Pheophyceae class.

Pheophyceae, or Phaeophyceae, are brown algae from the phylum Ochrophyta. They are also referred to as “brown algae”.

Advantageously, the extract comes from at least one plant belonging to a species chosen from the genera Fucus, Laminaria, Ascophyllum, Sargassum, Himanthalia, Pelvetia, Undaria, Alaria, Durvillea, Macrocystis, Lessonia, Ecklonia, Saccorhyza, Padina, Cystoseira .

Preferably, the extract comes from at least one plant belonging to a species chosen from Fucus vesiculosus, Laminaria hyperborea, Ascophyllum nodosum, Sargassum muticum, Pelvetia canaliculata, Undaria pinnatifada, Alaria esculenta, Durvillea antartica, Macrocystis pyrifera, Lessonia nigrescens, Ecklonia cava, Saccorhyza polyschides, Padina pavonica, Cystoseira tamariscifolia .

More preferably, the extract comes from Sargassum muticum.

The inventors of the present invention have thus demonstrated, using in vitro tests, that an aqueous extract of Pheophyceae, according to the invention, is capable of restoring the microbiota, of reducing the formation of biofilm of one of the forms virulent C. acnes , phylotype IA1, to significantly reduce the size and number of skin pores, signs of a reduction in hyperkeratinization disorders, and consequently to improve the appearance of the skin, in particular the skin texture, and restore optimal barrier function.

The inventors have also demonstrated that an extract according to the invention is capable of limiting lipid peroxidation induced by atmospheric pollutants, as well as inflammation induced by irritant agents such as SLS, a skin irritant agent widely used in cosmetic.

Advantageously, the extract according to the invention is characterized in that it comprises polyols, in particular mannitol and/or xylitol and/or glycerol, as polyols.

Advantageously, the extract has at least one of the following characteristics, the percentages being by weight relative to the raw weight of the extract:

a polyol content of between 1 and 70%, preferably between 5 and 50% of the dry matter of the extract;

a mannitol content of between 5 and 50%, preferably between 10 and 40% of the dry matter of the extract;

a xylitol content of between 0.01% and 10%, preferably between 0.05 and 5% of the dry matter of the extract;

a glycerol content, between 0.1 and 20%, preferably between 1 and 10% of the dry matter of the extract.

The extracts according to the invention can thus be clearly identifiable due to their polyol content. As an illustration, the polyol contents of brown algae of the Pheophyceae class are presented in Table 1 below which presents the polyol compositions, expressed in grams per 100g of dry matter, measured in different species of algae. The polyol composition was determined by ion chromatography and pulse amperometry (HPAEC-PAD).

Species Mannitol (%/DM) Xylitol (%/MS) Glycerol (%/MS) Alaria esculenta 10.24 ND ND Ascophyllum nodosum 11.23 ND ND Ectocarpus siliculosus 6.31 ND ND Fucus serratus 7.14 ND 1.06 Fucus spiralis 14.75 ND 1.13 Fucus vesiculus 5.53 ND 1.32 Halidrys siliquosa 8.36 ND ND Laminaria digita 12.44 ND 0.56 Laminaria saccharina 18.21 ND 0.23 Pelvetia canaliculata 7.03 ND ND Pylaiella littoralis 18.22 ND ND Sargassum muticum 26.72 0.16 1.78

The preparation of the aqueous extracts used in accordance with the invention can be carried out by conventional and well-known liquid phase extraction processes (maceration, decoction, infusion), in particular using polar solvents such as glycols (glycerols, propylene). glycol, propane diol, butane diol) or buffered water. Such processes are well known to those skilled in the art.

By way of non-limiting example, an extract according to the invention can be obtained by drying the fresh raw material; followed by grinding, maceration in water and filtration. Each step is generally carried out under controlled conditions of agitation, temperature, pH and time.

In more detail, the extraction process below can be implemented:

Fresh or dry algae are crushed using tools such as conventional grinders or by ultrasound. The extraction can possibly be preceded by enzymatic hydrolysis (proteases, glucanases, etc.) in order to improve the extraction yield. The extraction is carried out with static stirring in a plant/solvent ratio which can vary from ½ to 1/20, at temperatures varying from room temperature to 80°C, and over a period which can range from 30 minutes to 24 hours. . The extraction can optionally be carried out under microwave or subcritical and supercritical solvent. Once extracted, the solid residue of the algae is separated from the extractive solution by decantation or centrifugation. The extract is then filtered through a membrane.

The extract, whatever the extraction method, can then be dissolved in a polar solvent, such as a glycol, for example propylene glycol or a mixture of glycol and water.

Thus, according to a preferred embodiment of the invention, the extract is in solution in a polar solvent, in particular a glycol, such as glycerol, propanediol, butanediol or propylene glycol, or a mixture of glycol and of water.

The addition of glycerol is a very advantageous embodiment. Glycerol is in fact a substrate promoting the growth of S. epidermidis, a key bacterium in the balance of the microbiome via the production of bacteriocins which modulate the growth of the virulent IA1 phylotype of C. acnes (Dagnelie et al., 2019; Coenye et al. al., 2022).

According to one embodiment of the invention, the extract is formulated in a composition, preferably topical, in which the quantity of extract is greater than or equal to 0.01% and less than or equal to 5% by weight, preferably between 0.1 to 3%, relative to the total weight of the composition.

Advantageously, the cosmetic composition is in the form of a cream, an oil-in-water emulsion, a water-in-oil emulsion, a multiple emulsion, a solution, a gel, a suspension, a spray or powder.

Such a composition may of course include one or more other compounds such as dyes, film-forming agents, surfactants, perfumes, preservatives, emulsifiers, oils, UV filters, vitamins, or any other suitable compound. for the cosmetic application of the composition.

The characteristics of the invention mentioned above, as well as others, will appear more clearly on reading the following description of exemplary embodiments.

EXAMPLES

Example 1: example of a method for obtaining an aqueous extract according to the invention

We incorporate 100 kg of Pheophyceae in 200 kg of water. Grinding is carried out using an Ultra-turrax type grinder for 12 hours at room temperature. The extraction is carried out with stirring for 24 hours at room temperature, then the solution is filtered.

Example 2: example of a method for obtaining an aqueous extract according to the invention

100 kg of Pheophyceae are incorporated into 200 kg of 1,3-propanediol. After ultrasonic micro-grinding, the extraction is carried out with stirring for 4 h at 50°C, then the solution is centrifuged and filtered.

Example 3: example of a method for obtaining an aqueous extract according to the invention

100 kg of Pheophyceae are incorporated into a reactor in 500 kg of buffered water at pH: 6. An enzymatic preparation containing a mix of proteases and glucanases is added. Hydrolysis is carried out for 3 hours at 50°C. At the end of the reaction, the enzymes are denatured at 90°C for 15 minutes. The algae pulp recovered after centrifugation is taken up in a propanediol solution at a rate of 100 kg. The extraction is carried out with stirring for 24 hours at room temperature, then the solution is filtered.

It is observed in particular that an aqueous extract of Sargassum muticum according to the invention contains a total greater than 20%/MS of polyols. The contents of polyols and mainly mannitol are known in Sargassum species not to exceed 14%/DM (Devault et al., 2020).

Example 4: in vitro studies demonstrating inhibition of biofilm formation of C. acnes phylotype IA1

The objective of the study is to evaluate the capacity of an aqueous extract of Pheophyceae to inhibit the formation of a biofilm of the C. acnes IA1 strain, the majority strain present in the case of acne-prone skin.

Operating mode:

The aqueous extracts used are an extract of Sargassum muticum (SAM) obtained according to the extraction process presented in Example No. 2, an aqueous extract of Pelevetia canaliculata and an aqueous extract of ulva lactuca.

The anti-biofilm effects of this aqueous extract were investigated, evaluating the formation of a biofilm of the strain considered, alone and compared to a positive control and other extracts.

C. acnes IA1 is first cultured until it reaches its exponential growth phase, under anaerobic conditions. The bacterial suspension is normalized via an optical density of 1. The analysis is carried out in 96-well plates. The wells are seeded and cultured for 2 hours at 37°C with C. acnes IA1. This step consists of achieving primary adhesion of the strain. Subsequently and after washing the wells, the bacteria are cultivated for 3 days at 37°C, under three conditions: without any treatment or in the presence of a recognized inhibitor of C. acnes or the Sargassum extract of the invention. muticum (control, positive control and extract).

After 3 days, the plates are washed in order to eliminate the “planktonic” forms of bacteria, that is to say those remaining in suspension, and crystal violet is used at 0.1% to mark the biofilms fixed with methanol.

Quantification of biofilms is obtained using optical density reading at 600 nm by spectrocolorimetry (DO600). The rate of inhibition of biofilm formation by the extract was calculated, compared to control conditions (untreated), according to the formula: ((OD600 Biofilm treated – OD600 Biofilm Untreated) / OD600 Biofilm Untreated) x 100.

The experiments were carried out in triplicate (n=3) and statistical analysis was carried out by a t-test or paired Student's test for the comparison of treated versus untreated conditions (controls).

Results :

The results are presented in Table 2.

Plant/algae extracts Reference % inhibition of C. acnes IA1 biofilm formation t-test
(Versus untreated control) Pelevetia canaliculata PEC 27 P<0.05 Sargassum muticum SAT 35 P<0.05 Ulva lactuca ULL 0 /

The positive control demonstrated 80% inhibition of biofilm formation, allowing the experiment to be validated.

Thus, the use of an extract according to the invention, in particular of Sargassum muticum , makes it possible to reduce the appearance of biofilm of the phylotype IA1 of C. acnes , known for its virulence in situations of severe acne.

Reducing the formation of these biofilms will reduce the quantity of bacteria in the pilosebaceous units and consequently limit the release of virulence factors of the IA1 C. acnes phylotype involved in the activation of TLRs and inflammation signaling pathways. .

Example 5: In vitro studies demonstrating the inhibition of lipid peroxidation induced by atmospheric pollution

To evaluate the reduction in the oxidative reaction due to environmental stress, in particular pollution, the lipid oxidation capacity was analyzed on skin explants.

The objective of this study is to evaluate the capacity of an aqueous extract from Pheophyceae algae to reduce lipid oxidation via the formation of MDA (Malondialdehyde), but also to observe the morphological changes of the layers of the skin following stress induced by environmental pollutants.

The aqueous extract used is the extract of Sargassum muticum (SAM) obtained according to the extraction process presented in Example No. 2.

Operating mode:

The human explants came from an abdominoplasty of a 66-year-old female individual, corresponding to phototype II according to the Fitzpatrick classification. 3D models of human skin explants were used to evaluate the protective effect of Sargassum muticum extract against the deleterious effects of environmental pollutants.

The SAM extract was applied topically to the explants in culture (2 µL/cm2) on D0, D2 and D5. The unstressed, untreated “control” explants did not receive any application of SAM extract or polluting stress. After 5 days of incubation at 37°C, certain explants are stressed for 1h30 using agents present in atmospheric pollution in the form of smoke, including heavy metals and polycyclic aromatic hydrocarbons (Benzene, Xylene, Toluene). , using the PolluBox® device. The final concentration of heavy metals is between 0.0005 mg/mL to 0.05 mg/mL, that of hydrocarbon compounds is 1 µL/mL. The explants are then collected.

Histological studies carried out from 5µm sections of fixed and paraffin-embedded explants made it possible to evaluate the morphology and integrity of the tissues and to estimate viability.

The determination of malondialdehyde (MDA) according to the method of Conti et al (Improved fluorimetric determination of malonaldehyde., Clinical Chemistry, 1991), made it possible to evaluate the oxidation or peroxidation of lipids. It reflects the degree of oxidative damage caused to cellular components by environmental pollution. A high level of MDA indicates a state of oxidative stress. It is expressed in nmol/L. MDA is measured by fluorescence spectroscopy following a reaction with diethylthiobarbituric acid (DETBA).

The rate of induction of MDA by polluting agents was calculated, compared to the conditions of unstressed controls according to the formula: ((Concentration MDA Stressed and untreated – Concentration MDA unstressed and untreated) / Concentration MDA unstressed and Untreated) x 100.

The rate of inhibition of MDA production by the SAM extract was calculated, compared to the conditions of controls stressed by pollutants according to the formula: ((Concentration MDA Stressed and Treated – MDA Concentration Stressed and Untreated) / Concentration MDA Stressed and Untreated) x 100.

Explants stressed by pollutants showed a significant increase of 297% in MDA levels. Explants stressed and treated with SAM showed a significant inhibition of 47% in MDA level compared to stressed and untreated explants.

Results :

The results are indicated in Table 3: MDA dosage result of skin explants treated or not with pollutant stress (*:p<0.05 compared to the control condition + Pollution).

MDA dosage in nmol/L Witness Witness + Pollution Witness + Pollution + SAM extract Average 245 971 514 Standard deviation 152 188 87 t-test (Versus control) / P<0.001 P<0.05*

Morphological observations showed that treatment with polluting compounds seems to alter the integrity of the epidermis and dermis of the explants, with a disruption of cohesion between cells (living layers and the stratum corneum ) and a lower density of collagen fibers in the dermis, respectively. It is indeed known that pollution induces an inflammatory state which is accompanied not only by the production and release of mediators such as cytokines, but also by the activation of the expression of matrix metalloproteinases, responsible for the degradation of the matrix. extracellular.

Treatment with SAM preserved morphological alterations induced by pollutants and preserved the integrity of the epidermis and dermis.

Thus, the cosmetic or dermatological use of an extract according to the invention makes it possible to reduce the oxidation of lipids, in response to oxidative stress induced by atmospheric pollution. This therefore makes it possible to preserve the components of skin cells (DNA, proteins, lipids) and their functionality in the face of environmental stress, in order to maintain tissue integrity for healthy skin.

Example 6: in vitro studies demonstrating inhibition of IL-1α release induced by SLS, a skin irritant

Among the stresses to which the skin is subjected, certain surfactants with detergent actions can cause skin irritation, such as SLS, widely used in cosmetics. In the case study, SLS is thus used as a model for the induction of skin inflammation. At the molecular level, these irritations are characterized by the activation of inflammatory pathways leading to the release of pro-inflammatory mediators such as cytokines including IL-1α.

The objective of this study is to evaluate the capacity of an aqueous extract rich in polyols from Pheophyceae algae to reduce inflammation via the evaluation of the synthesis and release of IL-1α induced by topical application. of SLS.

The aqueous extract used is an extract of Sargassum muticum (SAM) obtained according to the extraction process presented in Example No. 2.

Operating mode

To evaluate the anti-inflammatory properties of the SAM aqueous extract, 3D models of human skin explants were used to evaluate the protective effect against the irritant effects of SLS. The SAM extract was applied topically to the explants in culture (2 µL/cm2) on D0, D1 and D4. The “control” explants did not receive any application of SAM extract or SLS treatment. On the 4th day, in order to induce skin inflammation, a patch containing 30 μL of 5% SLS is applied to the surface of the explants for 24 hours. On D5, the explants are recovered, fixed for histological analyses, and the supernatants are collected for the IL-1α assay.

The determination of IL-1α released by the explants in the culture supernatants was carried out using the ELISA kit (Cayman, ref. 583301). The sample is placed in the presence of acetylcholinesterase (AChE) and the IL-1α antibody. Subsequently, the sample is washed and a revealing solution containing an acetylcholinesterase substrate allows observation of absorbance at 412 nm.

The release rate in the supernatants of IL-1α induced by SLS was calculated, compared to the conditions of non-SLS stressed controls, according to the formula: ((IL-1α Concentration Stressed and Untreated – IL-1α Concentration (unstressed and untreated) / IL-1α concentration (unstressed and untreated) x 100.

The rate of inhibition of IL-1α release by the SAM extract was calculated, relative to the conditions of controls stressed by SLS, according to the formula: ((IL-1α Concentration Stressed and Treated – IL Concentration -1α Stressed and Untreated) / IL-1α Concentration Stressed and Untreated) x 100. Explants stressed by the patch containing 5% SLS showed a significant 531% increase in IL-1α release into the supernatant of culture. SLS-stressed and SAM-treated explants showed a significant 58% inhibition of IL-1α release into the culture supernatant compared to SLS-stressed and untreated explants.

Results :

The results are presented in Table 4: Dosage of the IL-1α marker by Elisa method on skin explants (*:p<0.05 compared to the control condition + inflammation; ns: not significant).

IL1-α dosage in pg/mL Witness SAT Witness + Inflammation Witness + Inflammation + SAM Average 3.2 5.7 20.2 8.5 Standard deviation 1.1 1.9 7.1 4.1 t-test (Versus control) / ns P<0.05 P<0.05*

Thus, the cosmetic or dermatological use of the invention makes it possible to reduce the inflammatory response, in response to an irritating agent. These results indicate that the invention limits the activation of inflammation signaling pathways such as the NFkB transcription factor pathway, of which IL-1α is not only a target but also an activator.

Example 7: in vivo clinical studies demonstrating improvement in skin texture and texture via reduction in pore density, diameter and surface area

The objective of this study is to evaluate the ability of an aqueous extract rich in polyols from Pheophyceae algae to reduce the size and number of pores in the skin. The hyperkeratinization disorders observed at the level of the pores generate conditions favorable to colonization by C. acnes . The accumulation of keratins, sebum and potentially the formation of biofilms obstruct pores (comedones or whiteheads) and promote their dilation and appearance. The skin then appears grainy and unsightly due to irregular skin texture. In addition, these lesions can degenerate into pro-inflammatory lesions (papules, pustules, nodules or cysts) responsible for the appearance of scars and the appearance of post-inflammatory hyperpigmentation spots and the loss of homogeneity of the complexion.

The aqueous extract used is the extract of Sargassum muticum (SAM) obtained according to the extraction process presented in Example No. 2.

Operating mode:

A clinical study carried out on female volunteers, aged on average 34.9 years, with oily, acne-prone skin and living in an urban area, made it possible to evaluate the effects of SAM extract in a gel versus placebo (the gel without the extract) on the appearance of pores, after 28 days of twice-daily application.

The VISIA System (Canfield) was used to measure the density, diameter and surface area of pores, as well as spots and homogeneity of the skin. The VISIA is a photographic booth used for the face. It allows images to be obtained under visible and cross-polarized light with standardization ensured by a computer-assisted repositioning system and perfect reproducibility of photographic conditions. From the before/after shots, it is possible to obtain multiple parameters, including the density, diameter and surface area of the pores, as well as the spots and an assessment of the homogeneity of the skin.

Results :

The results are presented in Table 5: all pore parameters measured on the skin of volunteers (ns: not significant).

SAT PLACEBO Freeze Pore measurement parameters J0 D28 %J28 versus J0 P value J0 D28 %J28 versus J0 P value Pore density (%) 100 88.38 -11.6 P<0.01 100 99.41 -0.58 NS Pore diameter (%) 100 94.87 -5.2 P<0.01 100 100 0 NS Pore area (%) 100 87.75 -12.2 P<0.01 100 98.04 -1.96 NS Pore homogeneity (%) 100 108.7 8.7 P=0.09 100 100 0 NS Number of buttons (%) 100 88.29 -12 P<0.01 100 98.64 -1.36 NS

After 28 days of twice-daily application, the gel containing SAM extract significantly reduced pore density, diameter and surface area by 11.6%, 5.2% and 12.2%, respectively. The number of buttons was significantly reduced by 12% and the homogeneity improved by 8.7% and not significantly (t-test, p=0.087). The placebo gel demonstrated no significant effect.

Clinical tests have demonstrated the ability of SAM extract in a gel to reduce the density, diameter, and surface area of pores in oily, acne-prone skin, demonstrating its pore-reducing properties, certainly due to its properties. anti-biofilm of C. acnes phylotype IA1. In addition, homogeneity tends to be improved and the number of spots reduced, which demonstrates an improvement in skin imperfections.

The properties described above (antioxidants, anti-inflammatory) also ensure healthy skin, that is to say whose homeostasis and integrity are respected for a reinforced skin barrier.

Claims (8)

Aqueous extract from at least one plant of the Pheophyceae class and belonging to a species chosen from the genera Fucus, Laminaria, Ascophyllum, Sargassum, Himanthalia, Pelvetia, Undaria, Alaria, Durvillea, Macrocystis, Lessonia, Ecklonia, Saccorhyza, Padina , Cystoseira, for its use in the treatment of acne-prone skin. Use of an aqueous extract from at least one plant of the Pheophyceae class belonging to a species chosen from the genera Fucus, Laminaria, Ascophyllum, Sargassum, Himanthalia, Pelvetia, Undaria, Alaria, Durvillea, Macrocystis, Lessonia, Ecklonia, Saccorhyza, Padina, Cystoseira for the care and improvement of oily skin, in particular to improve the texture of the skin, maintain the microbiota, to reduce the size and number of pores, to prevent or treat inflammatory reactions due to environmental factors such as UV rays, air pollution or skin irritants such as sodium dodecyl sulfate. Extract according to one of the preceding claims, characterized in that said extract comes from at least one plant belonging to a species chosen from Fucus vesiculosus, Laminaria hyperborea, Ascophyllum nodosum, Sargassum muticum, Pelvetia canaliculata, Undaria pinnatifada, Alaria esculenta, Durvillea antartica, Macrocystis pyrifera, Lessonia nigrescens, Ecklonia cava, Saccorhyza polyschides, Padina pavonica, Cystoseira tamariscifolia . Extract according to one of the preceding claims, characterized in that it comprises mannitol and/or xylitol and/or glycerol, as polyols. Extract according to one of the preceding claims, characterized in that said extract has at least one of the following characteristics, the percentages being by weight relative to the gross weight of the extract:
a polyol content of between 1 and 70%, preferably between 5 and 50% of the dry matter of the extract;
a mannitol content of between 5 and 50%, preferably between 10 and 40% of the dry matter of the extract;
a xylitol content of between 0.01% and 10%, preferably between 0.05 and 5% of the dry matter of the extract;
a glycerol content of between 0.1 and 20%, preferably between 1 and 10% of the dry matter of the extract. Extract according to one of the preceding claims, characterized in that said extract is in solution in a polar solvent, in particular a glycol, such as glycerol, propanediol, butanediol or propylene glycol, or a mixture of glycol and 'water. Extract according to one of the preceding claims, characterized in that said extract is formulated in a composition, preferably topical, in which the quantity of extract is greater than or equal to 0.01% and less than or equal to 5% by weight, preferably between 0.1 to 3%, relative to the total weight of the composition. Extract according to one of the preceding claims, characterized in that said composition is in the form of a cream, an oil-in-water emulsion, a water-in-oil emulsion, a multiple emulsion, a solution, a gel, suspension, spray or powder.