WO2025051825A1 - Composition based on pomegranate extract associated with probiotics, intended to correct skin disorders caused by pollution and/or uv radiation - Google Patents

Abstract

The present invention relates to a composition based on pomegranate extract associated with probiotics, intended to correct skin disorders caused by pollution and/or UV radiation.

Description

Description

Title of the invention: Composition based on pomegranate extract combined with probiotics, intended to correct skin disorders caused by pollution and/or UV rays

[0001] The present invention relates to a composition based on pomegranate extract combined with probiotics, intended to correct skin disorders caused by pollution and/or UV rays.

[0002] State of the art

[0003] The skin is the largest organ in humans, and one of its most important functions is to act as a barrier to protect the body from environmental fluctuations, including bacterial infections. The protective barrier function of the skin is constituted by the epidermis and the innate immunological functions of the host, including the microbiota living on and in the skin.

[0004] Skin barrier function can be affected not only by external environmental factors, such as temperature, humidity, ultraviolet (UV) rays, pollution and chemicals, but also by various other factors, including aging, psychological stress, nutritional status and the physiological state of the body.

[0005] Although the majority of microorganisms that live on human skin are harmless or even beneficial since they constitute the commensal microflora that makes up the microbiota, some resident microorganisms are potentially opportunistic, or even pathogenic under certain conditions. For example, Staphylococcus aureus, which is a common cause of cutaneous and systemic infections, resides in the skin of healthy individuals as a commensal strain, but can opportunistically colonize the lesional skin of ~90% of cases of atopic dermatitis (AD) and other dermatoses such as psoriasis and acne vulgaris.

[0006] As with the intestine, the skin barrier forms a tight barrier that controls external stimuli, including microorganisms. Structural alteration of the barrier function (leaky skin syndrome) could be one of the First signs of microbiota imbalance and explain most dermatoses. Thus, unhealthy skin is characterized in particular by a microbial imbalance (or dysbiosis) which can cause, as in the intestine, intercellular "cracks" in the stratum corneum and the deeper layers of the epidermis, allowing, for example, external elements to penetrate the body while reducing the skin's ability to renew itself. This structural state is called "leaky skin syndrome". This intercellular alteration particularly concerns the protein structure of tight junctions and in particular the alteration of proteins such as claudins (different subtypes) and occludin. This alteration is caused in cases of dysbiosis by proteases produced by opportunistic or pathogenic bacteria. Staphylococcus aureus or Staphylococcus epidermidis can be part of these opportunistic bacteria. Other types of aggression will be more chemical and/or physical in nature, particularly with external aggressions such as UV rays or pollutants.

[0007] To maintain and improve the health status of the skin, a wide variety of skin care products are on the market but none of them have tried to specifically repair/protect the structural alterations induced by dysbiosis of aging skin and aggravated by pollution and UV.

[0008] Aging, especially that induced by pollution (i.e. environmental aggressions), is considered a "snowball" phenotype characterized by the accumulation of damaged, dysfunctional or toxic proteins and silent mutations (polymorphisms) that sensitize the proteins concerned to oxidative damage as innate predispositions to age-related diseases, including in the aging of skin and hair. Aging is not a disease, but it causes (or shares a common cause) with chronic age-related diseases.

[0009] The fact i) of considering this aging induced by environmental pollution, as an initially silent protein polymorphism which becomes phenotypic and causes chronic age-related diseases in a polluted environment and ii) of suggesting that protein damage can lead to alterations of the genome, leads to proposing (when this phenomenon appears in the skin), new cosmetic, dermatological and nutri-cosmetic applications. These so-called "proteo-protective" applications are intended to combat skin disorders and skin diseases associated with pollution over time.

[0010] Existing products on the market, such as moisturizers, sunscreens and anti-aging products, may offer some benefits, but they do not necessarily address the specific needs of skin disorders caused by pollution and UV rays. Therefore, there is still a need for more effective, targeted and natural products to treat these specific skin problems.

[0011] Description of the invention

[0012] The present invention relates to novel compositions for correcting skin disorders caused by exposure to pollution and/or ultraviolet (UV) rays. More particularly, the invention relates to a composition comprising at least one extract of Punica granatum (pomegranate) and at least one probiotic. This synergistic combination of natural active ingredients offers significant benefits for improving the condition of the skin and mitigating the harmful effects of environmental pollution and UV rays. More particularly, the present invention makes it possible to strengthen the protective function of the skin, improve its elasticity and reduce the visible signs of damage caused by pollution and UV rays.

[0013] The composition according to the invention has many advantages over existing solutions. It offers a comprehensive approach to treating skin disorders linked to pollution and/or UV rays by acting both on the repair of damaged skin and on protection against new attacks. In addition, the natural ingredients used in the composition minimize the risks of adverse effects and are suitable for different skin types.

[0014] The composition according to the invention is intended for topical use and comprises

- from 1% to 40% by weight of at least one extract of Punica granatum and;

- from 1% to 65% by weight of at least one probiotic.

[0015] The pomegranate tree {Punica granatum) is a small fruit tree with deciduous foliage, native to Asia, particularly the Middle East, belonging to the family of Punicaceae. It can reach about 5 m, but often does not reach more than 1.50 m. The flowers are reddish-orange or scarlet, single or double, depending on the variety. The fruits are edible and have been eaten since ancient times. Synonyms are Punica spinosa, Punica florida or Granatum puniceum.

[0016] Its fruit is the pomegranate, reddish-orange in color, with a hard, leathery pericarp (or rind) containing in 6 to 12 membranous chambers numerous triangular seeds with a translucent and juicy ari Ile. The pomegranate (Punica granatum) is a member of the Lythraceae family, subfamily Punicoideae. In the form of intact juice, the pomegranate is generally used in baking, cooking, juice blends, meal toppings, smoothies, and alcoholic beverages, such as cocktails and wine. The red color of the juice is attributed to anthocyanins, such as delphinidin and cyanidin glycosides. In general, an increase in juice pigmentation occurs during fruit ripening. This increase is induced by the oxidation of anthocyanins. The pomegranate is rich in vitamins (B, C, and D) and polyphenols in the form of tannins. Bark extracts have been proposed for their astringent, antibacterial, and antihemorrhagic properties.

[0017] Pomegranate peel contains a high number of polyphenols, condensed tannins, and catechins. These pomegranate polyphenols provide protection against oxidative damage. The most abundant are hydrolyzable tannins called ellagitannins or punicalagins that occur when ellagic acid and gallic acid bind to a carbohydrate to form pomegranate ellagitannins, also called punicalagins. The higher phenolic content of the peel thus allows for extracts that can be used in dietary supplements and food preservatives.

[0018] Pomegranate seed oil is also rich in punicic acid, a specific C18, n-5 acid with very high antioxidant capacity. Pomegranate seed oil contains punicic acid (65% to 85% by weight), palmitic acid (5%), stearic acid (2%), oleic acid (6%), and linoleic acid (7%).

[0019] The wealth of antioxidant compounds present in pomegranate helps protect human cells from damage caused by radicals free, which may help prevent chronic inflammation associated with an increased risk of chronic diseases over time, in a polluting environment.

[0020] According to one embodiment, at least one extract of Punica granatum according to the invention comprises ellagitannins (including punicalagins), ellagic acid (derived from ellagitannins) and punicic acid.

[0021] Surprisingly, the present inventors have discovered that a combination between at least one extract of Punica granatum (in solid, aqueous, alcoholic and hydroalcoholic and/or oily form) and at least one probiotic (live, in the form of partial or total extracts such as postbiotics and/or in the form of culture supernatant) makes it possible to correct skin damage caused by pollution and UV rays in the skin.

[0022] According to one embodiment, the composition is intended for topical use and comprises:

- between 1 and 20%, preferably between 1% and 10%, more preferably between 1% and 5% by weight of at least one extract of Punica granatum and;

- from 1% to 15%, preferably between 1% and 10%, more preferably between 1% and 5% by weight of at least one probiotic including the extracts and/or supernatants and/or culture medium of said probiotics and/or complete microbial culture lysates

[0023] According to one embodiment of the invention, the composition according to the invention is intended for topical use and the pomegranate extract is an extract of the fruit of Punica granatum, or of its fractions and/or is in the form of oil preferably obtained from the seeds of the fruit Punica granatum. The pomegranate seed oil may comprise between 30 and 90% by weight of punicic acid. The seed oil rich in punicic acid is thus particularly suitable for the invention. In particular, an oil extracted from pomegranate seeds containing, by total weight of the oil, at least 30% by weight of punicic acid is used.

[0024] Extraction from the pomegranate fruit including the seed can result, according to a particular method of production, in the preparation of an oil. The extract in the form of a concentrated solution, as well as the extract in the form of powder, of as well as the extract in oil form can be used in a medium suitable for application to the skin or its appendages or for oral administration.

[0025] According to one embodiment of the invention, at least one extract of Punica granatum is in the form of oil, preferably seed oil of the Punica granatum fruit comprising (titrated), by total weight of the extract, between 30 and 90%, preferably between 60% and 85% by weight of punicic acid. Punicic acid is a powerful antioxidant, which means that it helps to neutralize free radicals present in the skin. Punicic acid therefore helps to protect the skin by reducing the damage caused by these free radicals. Punicic acid also has anti-inflammatory properties. Punicic acid thus helps to soothe and reduce inflammation, thus promoting calmer and less reactive skin. Punicic acid also has moisturizing properties and helps to strengthen the skin barrier. In addition, this acid can stimulate cell regeneration, thus promoting smoother and more radiant skin. Punicic acid can also promote the healing of damaged skin. It helps stimulate the production of collagen, a protein essential for skin structure and elasticity. By promoting healing, it can help fade scars, dark spots, and other signs left by skin disorders.

[0026] By combining punicic acid with other active ingredients, such as probiotics according to the present invention, the composition benefits from a synergy of effects which contributes to improving the condition of the skin and correcting skin disorders caused by pollution and/or UV rays.

[0027] According to another aspect of the description, the composition is intended for oral use and comprises

- from 1% to 40% by weight of at least one extract of Punica granatum and;

- from 1% to 65% by weight of at least one probiotic.

[0028] According to one embodiment, the composition described is intended for oral use and comprises between 15 and 40%, preferably between 20% and 40%, more preferably between 25% and 40% by weight of at least one extract of Punica granatum and; from 40% to 65%, preferably between 45% and 60%, more preferably between 50% and 60% by weight of at least one probiotic including the extracts and/or supernatants and/or culture medium of said probiotics and/or complete microbial culture lysates

[0029] According to another embodiment of the invention, the composition described is intended for oral use and at least one extract of Punica granatum is in the form of a dry extract comprising between 20 and 85%, preferably between 30% and 75% by weight of polyphenols, in particular ellagic tannins called punicalagins. Punicalagins are complex water-soluble tannins formed from a glucose linked to ellagic acid and gallagic acid. Polyphenols are natural antioxidant compounds present in many foods of plant origin, including pomegranate. They help protect the skin against free radicals, which are unstable molecules produced by factors such as pollution and UV rays. By neutralizing free radicals, polyphenols help reduce oxidative damage and thus prevent premature aging of the skin. Polyphenols also have anti-inflammatory properties. Polyphenols help soothe skin inflammation, reducing redness, irritation, and inflammatory reactions. This anti-inflammatory action helps keep skin calmer and less prone to inflammation-related skin problems. The polyphenols in pomegranate are also known for their ability to protect the skin from damage caused by air pollution. Environmental pollution, such as fine particles and chemical pollutants in the air, can damage the skin by causing cellular oxidation, inflammation, and a compromised skin barrier. Polyphenols help strengthen the skin's protection against these environmental aggressors, minimizing associated skin damage. Polyphenols may also offer some protection against the damaging effects of UV rays. Although they cannot replace the use of adequate sunscreen, polyphenols have demonstrated photoprotective properties by reducing UV-induced oxidative stress, helping to prevent cellular damage and supporting the repair of damaged DNA.

[0030] By integrating the polyphenols of the Punica granatum extract into the composition, it benefits from antioxidant properties, particularly on the protein residues, protection against environmental damage and the photoprotective effects of polyphenols. These benefits help improve the appearance of the skin, particularly by correcting skin disorders caused by pollution and/or UV rays.

[0031] According to one embodiment of the invention, at least one Punica granatum extract is in the form of a dry extract comprising between 20% and 70%, preferably between 30% and 55% by weight of hydrolyzable tannins of the ellagitannin type, also called punicalagins. Punicalagins, also called ellagic tannins, are polyphenols belonging to the large family of tannins and more precisely hydrolyzable tannins. They are characterized by the ability of the molecules to release ellagic acid after hydrolysis. By including the punicalagins from the dry extract of Punica granatum in the composition, we benefit from their antioxidant and UV protection properties.

[0032] According to one embodiment of the invention, at least one extract of Punica granatum is extracted or purified from the fruit of Punica granatum or its fractions and/or at least one extract of Punica granatum is in the form of a dry extract titrated in punicalagins and preferably obtained from the fruit of Punica granatum.

[0033] According to one embodiment of the invention, at least one Punica granatum extract is in the form of a dry extract comprising between 20% and 70%, more preferably between 30% and 55% by weight of punicalagins A and B. By including punicalagins A and B in the composition, one benefits from their antioxidant, photoprotective and potentially antimicrobial properties.

[0034] According to one embodiment of the invention, at least one Punica granatum extract comprises:

- between 30 and 90%, preferably between 60% and 85% by weight of punicic acid in an oily extract;

- between 20 and 85%, preferably between 30% and 75% by weight of polyphenols in a dry extract;

- between 20% and 70%, preferably between 30% and 55% by weight of hydrolyzable tannins of the ellagitannins or punicalagins A and B type in a dry extract; [0035] As indicated previously, the present invention is based on a combination between at least one extract of Punica granatum and at least one probiotic.

[0036] According to the invention, the term probiotic designates live lyophilized microbial probiotic strains as well as their extracts in liquid form in suspension and/or in the form of a soluble metabolite of said probiotic bacteria, and/or of a cell lysate of said probiotic bacteria, and/or in postbiotic form (i.e. said microbial strains in the form of total or partial extracts and/or "bioactive" molecules released into the culture medium) which can confer health benefits by strengthening innate immunity in particular. The probiotic strains used in the composition are organisms beneficial for skin balance and capable of providing positive effects on the skin when applied directly to the skin and/or orally.

[0037] These probiotics can belong to different bacterial or fungal strains that have been selected based on their specific properties to support the health and well-being of the skin.

[0038] Generally speaking, probiotic may, within the framework of this invention, designate the two forms: probiotic and post-biotic.

[0039] In the context of the invention, the term "postbiotic" refers to metabolites or bioactive substances produced by probiotic microorganisms during their growth and metabolic activity. These metabolites are released into the surrounding environment and may have beneficial effects on the skin. Postbiotics are the result of the activity of probiotics and may include enzymes, organic acids, peptides, polysaccharides, amino acids, vitamins, antioxidants and other bioactive substances. They are considered to be the products of the metabolism of probiotics.

[0040] The probiotics used in the composition can act in several ways, including strengthening the skin barrier, promoting the balance of the skin microbiota, regulating skin discomfort and improving the skin's immune response. It is well known that probiotics can have various beneficial effects on skin health and, in the prevention and treatment of skin disorders including eczema, atopic dermatitis, acne, allergic skin inflammation, skin hypersensitivity, UV-induced skin damage, wound healing and skin aging.

[0041] The activities of probiotics on the skin by topical application can be explained by i) a direct effect on the tissue by strengthening the physical barrier of the skin, ii) an effect via the so-called "bioactive" molecules released and iii) the induction by the skin of the production of antimicrobial peptides which promote innate cutaneous immune responses and eliminate pathogens and/or regulate opportunists of commensal origin.

[0042] By oral route, the activity on the skin can also be explained by i) the induction of natural defenses via the digestive tract and ii) the release of “bioactive” molecules which will be distributed to the skin via the bloodstream.

[0043] New evidence has recently demonstrated that probiotic bacteria exhibit significant antioxidant capacities and could thus be effective against oxidative events, which could be a further relevant element, to provide an overall beneficial effect against age-associated skin disorders, in particular induced by pollution and/or UVs.

[0044] According to one embodiment, the use of probiotics and their postbiotics in the composition makes it possible to benefit from the synergistic advantages of these bioactive substances. The postbiotics, as metabolic products of the probiotics, can act in synergy with the probiotics themselves to enhance the beneficial effects on the skin, thereby improving skin health and helping to correct skin disorders linked to pollution and/or UV rays.

[0045] According to one embodiment, at least one probiotic is in the form of a live, freeze-dried probiotic bacterium, a liquid suspension and/or a soluble metabolite of a probiotic bacterium, and/or a cell lysate of a probiotic bacterium, and/or a post-biotic.

[0046] According to one embodiment, the composition according to the invention comprises a mixture of probiotics.

[0047] According to one embodiment of the invention, at least one probiotic is selected from the group consisting of the following probiotic bacteria: Lactobacillus rhamnosus, Lactococcus sp., Lactococcus lactis, Lactobacillus rhamnosus GG, Lactobacillus casei, Lactobacillus gasseri, Lactobacillus plantarum, Bifidobacterium longum, Lactobacillus plantarum, Bifidobacterium adolescentis, Lactobacillus reuteri, Bifidobacterium infantis, and mixtures thereof, preferably Lactobacillus rhamnosus GG and Bifidi bacterium adolescentis.

[0048] According to one embodiment of the invention, the number of Colony Forming Units (CFU) per probiotic is between 1 and 40 billion, preferably 3 to 20 billion per capsule, more preferably 5 to 10 billion per capsule.

[0049] Lactobacillus plantarum is a versatile bacterium found in a variety of ecological niches, ranging from plant fermentations to the human gastrointestinal tract. Lactobacillus plantarum are rod-shaped with rounded, straight ends, typically 0.9-1.2 pm wide and 3-8 pm long, occurring singly, in pairs, or in short chains. The genome of the first bacterium isolated from a human gastrointestinal tract, L plantarum strain WCFS1, has been sequenced (Kleerebezem et al., PNAS 2003, vol. 100 volume 4; 1990-1995), and its size of 3.3 Mb is among the largest known for bacteria inhabiting the gastrointestinal tract (Makarova K. et al., PNAS 2006, 103 vol. 42; 15611-15616); Makarova and Koonin, J. Bacteriol.2007, tome189 vol.4 1199-1208). Such a genome length is thought to be related to the diversity of environmental niches in which L. plantarum is found.

[0050] Lactobacillus reuteri is a typical intestinal symbiotic bacterium that plays an important role in maintaining the stability of intestinal flora and host health.

[0051] Lactobacillus rhamnosus GG (strain ATCC53103) is an extremely well-studied probiotic strain. It was discovered in 1985 and numerous studies have proven more than 40 health benefits. Lactobacillus rhamnosus GG, has very good adhesion to the intestinal wall and is therefore considered a good probiotic. This probiotic stimulates the immune system, fights allergies and provides digestive benefit on Irritable Bowel Syndrome (IBS) and constipation.

[0052] The benefits of Lactobacillus rhamnosus GG are numerous: diabetes management, immune-boosting effects: fights bacterial infections, inhibits H. pylori-induced ulcers, stimulates general immunity, improves immunity in HIV/AIDS patients, decreases symptoms of HIV/AIDS.

[0053] The anti-inflammatory potential of Lactobacillus rhamnosus strain 4B15 and Lactobacillus gasseri strain 4M13 isolated from infant feces has also been recently described (Nam Su et al., PloSone, 2018 vol.13, tome 2 e0192021).

[0054] Bifidobacteria are natural inhabitants of the gastrointestinal tract with genetic adaptations that allow colonization of this difficult and complex habitat. Bifidobacteria interact with key elements of intestinal function and thus contribute to the maintenance of homeostasis. Due to their recognized benefits for human health, bifidobacteria are used as probiotics.

[0055] About a dozen strains of Bifidobacterium sp. with clinically documented effects are commercially available. Half of them are Bifidobacterium animalis subsp. Lactis and the others are Bifidobacterium longum subsp. Longum, B. longum subsp. Infantis or Bifidobacterium breve strains.

[0056] Bifidobacterium adolescentis was ^first isolated from the intestine of an adult (Reuter, Current Issues Intest. Microbiol. 2001; vol.2 T. 2;43-53). Strains of B. adolescentis are frequently detected in the adult human intestinal tract (Turroni et al., 2009 Apply Environnement Microbiol. 2009, vol.75 tome 6, pp 1534-1545).

[0057] Lactococcus lactis is a lactic acid bacterium whose metabolism is heterotrophic and anaerobic. It usually contains one or more plasmids carrying genes coding for environmental adaptation functions. Lactococcus lactis is a model bacterium for basic research which has been the subject of numerous studies for several decades. It is also the first lactic acid bacterium whose genome has been completely sequenced. Lactococcus lactis (formerly Streptococcus lactis) is one of the intestinal bacteria capable of producing the enzyme lactase. The unique characteristic of Lactococcus lactis is that it produces an antibiotic peptide: the lantibiotic nisin. Nisin has been shown to be more effective against Clostridium difficile than antibiotics such as vancomycin and metronidazole.

[0058] David Groeger et al, (Gut Microbes, 2013; vol.4; 325-339) show that oral administration of B.infantis strain 35624 modulates both gastrointestinal and non-gastrointestinal cytokine milieu in inflammatory disorders and in healthy subjects. Oral administration of B.infantis 35624 was sufficient to reduce both gastrointestinal and extra-intestinal systemic inflammatory biomarkers in inflammatory disorders.

[0059] The composition according to the present invention produces protective activities in the skin by a mode of action intervening via an inhibition of the oxidation of proteins and preferably the intracellular, nuclear and extracellular proteins of the skin, in particular those constituting the tight junctions (claudins of different subtypes and occludin).

[0060] The composition according to the present invention for combating chronic damage from pollution over time can be used in topical form in anti-aging and dermatological cosmetic compositions.

[0061] According to another aspect of the description, the composition described can be used in the form of an orally administrable composition (food supplement) to combat chronic damage from pollution over time.

[0062] According to one embodiment of the invention, the composition according to the invention comprises an effective amount of probiotic(s) to reduce the release and/or production of inflammation mediators, in particular the cytokines IL-6, TNFa and IL1 b which contribute negatively to aging via a microinflammation process called “inflammaging”.

[0063] According to one embodiment of the invention, the composition according to the invention comprises an effective amount of probiotic(s) for reducing innate defense disorders and in particular for reducing cutaneous dysbiosis and aging, caused by a polluting environment.

[0064] Another object of the invention is a cosmetic formulation for topical application, comprising the composition according to the invention as well as a cosmetically acceptable vehicle. [0065] Said cosmetically acceptable vehicle may be an oil-in-water or water-in-oil emulsion. Preferably, said vehicle may be selected from the group consisting of glycerin, butylene glycol, propylene glycol, water, jojoba oil, sweet almond oil, soybean oil, sunflower oil, and apricot oil.

[0066] Another object of the invention is the non-therapeutic use of the cosmetic formulation for topical application according to the invention, in the correction of skin disorders caused by pollution and/or UV rays, in particular chronic aging of the skin.

[0067] Another subject of the description is a cosmetic process comprising the topical application to the skin of a composition according to the invention comprising: a) an effective amount of at least one extract, preferably oily, of Punica granatum; b) an effective amount of at least one probiotic, preferably in the form of a lysate of the bacterial culture and c) a cosmetically acceptable vehicle, for cleansing and conditioning the skin, protecting and repairing the skin against the appearance of signs of aging or skin dryness, rejuvenating the skin or increasing the skin's natural production of beneficial antioxidants.

[0068] Another subject of the description is a solid or liquid nutritional supplement characterized in that it contains a composition according to the invention.

[0069] According to one embodiment of the description, the solid or liquid nutritional supplement for oral administration according to the invention is characterized in that at least one extract of Punica granatum comprises between 20% and 70%, preferably between 30% and 55% by weight of punicalagins (glycosylated form of ellagic acid).

[0070] According to one embodiment of the description, the solid or liquid nutritional supplement for oral administration according to the invention is characterized in that at least one extract of Punica granatum is derived from the solid residues (cakes) resulting from the extraction of oil from the seeds of Punica granatum. The cakes are the solid residues from the extraction of oil from the seeds or oleaginous fruits. They are the co-products of crushing, the process for manufacturing oil. [0071] The present invention takes advantage of these residual pomegranate cakes traditionally considered to be of little value by transforming them into a valuable source of active ingredients intended for the manufacture of a food supplement. The present invention thus proposes an innovative approach to the valorization of by-products resulting from the extraction of pomegranate oil. Indeed, the transformation of the punicalagins present in these cake extracts can lead to the endogenous production by transformation via in particular commensal bacteria of the digestive tract of the species Gordonibacter urolithinfaciens or of the species Ellagibacter isourolithinifaciens, of a substance currently described as one of the first anti-aging senolytics: urolithin

[0072] By cleverly exploiting these solid residues, which are generally rejected during the production of Punica granatum oil, this composition not only reduces waste, but also offers a valuable use of these previously underestimated raw materials. The active ingredients contained in Punica granatum oilcakes are therefore preserved and combined with one or more carefully selected probiotics, in order to create a composition beneficial for the skin.

[0073] The food supplement thus obtained is distinguished by its richness in natural bioactive compounds originating from the residues of Punica granatum, as well as by the potential benefits of the probiotics used in this association to protect, as is the case with bifidobacteria, the commensal strains which transform punicalagins into urolith in particular subtype A whose senolytic effects have been proven.

[0074] According to one embodiment, the food supplement according to the invention comprises a mixture of probiotics comprising at least Lactobacillus Rhamnosus GG and Bifidi bacterium adolescentis.

[0075] Another object of the invention is the non-therapeutic use of the cosmetic topical formula according to the invention, to correct subclinical or clinical oxidative disorders involved in aging caused in particular by environmental pollution and in particular the oxidative alteration of the proteins constituting the stratum corneum and the epidermis. [0076] Another object of the description is the non-therapeutic use of the solid or liquid nutritional supplement for oral administration according to the description, to correct subclinical or clinical oxidative disorders involved in aging caused in particular by environmental pollution and in particular the oxidative alteration of the proteins constituting the stratum corneum and the epidermis.

[0077] Another object of the invention is the non-therapeutic use of the cosmetic topical formula according to the invention, to correct cutaneous dysbiosis and/or subclinical or clinical disorders (i.e. dermatological) associated with these dysbioses and involved in particular in the aging of the skin and caused by a polluting environment.

[0078] Another object of the description is the non-therapeutic use of the solid or liquid nutritional supplement for oral administration according to the description, to correct cutaneous dysbiosis and/or subclinical or clinical disorders (i.e. dermatological) associated with these dysbioses and involved in particular in the aging of the skin and caused by a polluting environment.

[0079] Description of the figures

[0080] Figure 1: In situ visualization (on skin explant sections) of carbonylation levels (in red) vs. cell nuclei (in cyan, DAPI staining). Quantification of carbonylation levels on the skin explant is also presented as histograms with mean values and standard deviation from the mean. Statistics (ANOVA and Dunnett's post-hoc test for comparison with stress; *** p<0.001).

[0081] Figure 2: Quantification of carbonylation levels across different skin layers is presented as histograms with mean values and standard deviation from the mean. Statistics (ANOVA and post-hoc Dunnett's comparison test versus stress; *** p<0.001).

[0082] Examples

[0083] Example 1: Example of an anti-aging topical formula compatible with sensitive skin (in % of the overall formula): [0084] [Table 1]

[00851 Example 2: Example of an anti-aging topical formula compatible with sensitive skin (in % of the overall formula):

[0086] [Table 2]

Example 3: Example of an oral formula

[0087] Formulation in the form of a food supplement for one capsule:

- Probiotic blend: 200 mg (10 billion CFU) composed of

Bifidobacterium adolescentis 5 Billion CFU

Lactobacillus rhamnosus GG (ATCC53103) 5 Billion CFU

- Punica granatum, dry extract titrated at 40% by weight of punicalagins: 125 mg

- Selenomethionine 0.5%: 12.5 mg including selenium 150 pg

- Zinc Gluconate: qsp RDA.

- Shell: HPMC vegetable capsule, vegan, gastro-resistant.

[0088] Example 4: Example of oral formula

[0089] Formulation in the form of a food supplement for one capsule:

- Probiotic blend: 200 mg (10 billion CFU) composed of

Bifidobacterium adolescentis: 5 billion CFU

Lactobacillus rhamnosus GG (ATCC53103): 5 billion CFU

- Punica granatum, dry extract titrated at 40% by weight of punicalagins: 125 mg

- Selenomethionine at 0.5%: 12.5 mg including selenium 150 pg

- L-Cysteine: 50 mg

- Shell: HPMC vegetable capsule, vegan, gastro-resistant.

[0090] Example 5: Activity of the composition according to example 1.

[0091] We have demonstrated the capacity of a composition described according to example 1, to prevent oxidative damage to human fibroblasts and keratinocytes during oxidative stress.

[0092] Methods:

[0093] Isolated human skin cells were cultured in a specific culture medium and divided into several experimental groups, containing several replicates per group (n>4). [0094] Said replicas are exposed to oxidative stress +/- UV and several types of mixture were included in the present experiment. After the stress, the cells were fixed and the carbonylated proteins were labeled in situ with a specific fluorescent probe. The fluorescence emission was then detected and recorded using a fluorescence plate reader.

[0095] Data management and statistical analyses were performed using GraphPad software.

[0096] [Table 3]

[0097] Results: See Figure 1 and 2 and Table 3 - A significant increase in oxidized (carbonylated) proteins was observed after the so-called H2O2 +/- UV stress treatments of the cells. The formula of Example 1 demonstrated protective effects against protein oxidation induced by the stress used and described above.

[0098] Example 6: Dermatological efficacy of the composition according to example 1.

[0099] The purpose of this study is i) to verify the compatibility and dermatological acceptability and ii) to evaluate the qualities and effectiveness of the composition according to example 1, after application under normal conditions of use.

[0100] The tested composition was evaluated on twenty (20) subjects, aged 35 to 65 years, women, all skin types, presence of signs of aging.

[0101] Under the experimental conditions, repeated applications of the composition according to example 1 on a panel of 20 subjects did not induce any skin reaction and no feeling of discomfort.

[0102] Therefore, the product showed very good dermatological compatibility and acceptability during the 28 days of application, under normal conditions of use.

[0103] Clinical score (table 4)

[0104] Skin elasticity, skin firmness, and skin hydrated appearance were clinically measured at D+0, D+14 and D+28 of application.

[0105] The evolution of clinical scores is detailed in table 4 below.

[0106] [table 4]

¹ Comparison of Wilcoxon test versus DO

[0107] We therefore observe a:

1 - increase in clinical elasticity score of 82.1% and 67.1% after 14 and 28 days of application, respectively.

2- increase in clinical firmness score of 67.1% and 60.8% after 14 and 28 days of application, respectively.

3- increase in the hydrated appearance of the skin: clinical score of 36.5% and 43.2% after 14 and 28 days of application, respectively.

[0108] These results are statistically significant compared to D0.

[0109] In conclusion, according to the dermatologist, the composition according to the invention increases the skin appearance scores, i.e. the improvement of skin elasticity, skin firmness and the hydrated appearance of the skin after 14 and 28 days of application of the product.

[0110] Self-assessment (table 5)

[0111] Skin elasticity, skin firmness, and skin hydrated appearance were measured by the subjects on D+0, D+14, and D+28 of application.

[0112] The evolution of clinical scores is detailed in table 5 below.

[0113] [table 5]

¹ Comparison of Wilcoxon test versus DO

[0114] We therefore observe a:

1 - increase in self-assessment elasticity score of 59.4% after 28 days of application.

2- increase in self-assessment score of firmness by 56.1% and 81.0% after 14 and 28 days of application, respectively.

3- increase in the hydrated appearance of the skin by 93.4% and 106.6% after 14 and 28 days of application, respectively.

[0115] These results are statistically significant compared to DO.

[0116] In conclusion, according to the subjects, the composition according to the invention increases the skin appearance scores, that is to say the improvement of the elasticity of the skin, the firmness of the skin and the hydrated appearance of the skin after 14 and 28 days of application of the product.

Claims

CLAIMS: 1. Composition in a form suitable for topical use comprising - from 1% to 40% by weight of at least one extract of Punica granatum and; - from 1% to 65% by weight of at least one probiotic. 2. Composition according to claim 1, characterized in that at least one probiotic is selected from the group comprising the following probiotic bacteria: Lactobacillus rhamnosus, Lactobacillus rhamnosus GG, Lactobacillus casei, Lactobacillus gasseri, Bifidobacterium longum, Lactobacillus plantarum, Bifidobacterium adolescentis, Lactococcus sp, Lactococcus lactis, Lactobacillus reuteri, Bifidobacterium infantis, and mixtures thereof. 3. Composition according to any one of claims 1 to 2, characterized in that at least one extract of Punica granatum is extracted or purified from the fruit Punica granatum or its fractions and/or in that at least one extract of Punica granatum is in the form of oil preferably obtained from the seeds of the fruit Punica granatum. 4. Composition according to any one of claims 1 to 3, characterized in that at least one extract of Punica granatum is in the form of oil obtained from the seeds of the fruit Punica granatum comprising, by total weight of the extract, between 30 and 90%, preferably between 60% and 85% by weight of punicic acid. 5. A cosmetic formulation in a form suitable for topical application, comprising the composition according to any one of claims 1 to 4 and a cosmetically acceptable vehicle. 6. Formulation in a form suitable for topical application according to any one of claims 1 to 5 for its use in the correction of skin disorders caused by pollution and/or UV rays, in particular chronic aging of the skin.