Cosmetic Use of Solanum Lycopersicon Fruit (Tomato) Skin Extract

Abstract

The present invention relates to the cosmetic use of a lipophilic peel extract of Solanum lycopersicon fruit containing at least 5% by weight of amyrin, at least 1.5% by weight of sterols and up to 0.5% by weight of lycopene for maintaining, restoring and / or balancing or strengthening the natural defenses of the skin or mucous membranes.

Description

[Technical field]

[0001] The present invention relates to the cosmetic use of a peel extract of Solanum lycopersicum fruit (tomato) as an active ingredient for maintaining, restoring and / or balancing or strengthening the natural defenses of the skin or mucous membranes. [Background technology]

[0002] The skin barrier is composed of a physical barrier and a chemical barrier, both of which are involved in the skin's natural defense system.

[0003] The epidermis, the top epithelial layer of the skin, is composed of keratinocytes, which undergo a process of proliferation and differentiation to continually renew the upper layer of the skin. Epidermal keratinocytes play an important role as a barrier against a variety of environmental factors. In particular, the differentiation program of keratinocytes results in the formation of dead cells (corneocytes) in the top layer of the skin. A keratinized skin layer provides many benefits to the face and tissues, including increased elasticity, stability, moisture retention, and mechanical resistance.

[0004] A wide range of specialized cells, keratinocytes, melanocytes, tissue-resident leukocytes (dendritic cells) and soluble mediators such as antimicrobial peptides (AMPs) or lipid mediators (cytokines) contribute to the epidermal barrier.

[0005] The skin is the first barrier against viruses, bacteria, fungi, parasites, and toxins. Innate immune defense against pathogens is achieved by physical barriers, recruitment of cells such as neutrophils, NK cells, and macrophages, and by secretion of antimicrobial peptides. Three types of epidermal cells are involved in the immune response: keratinocytes, melanocytes, and Langerhans cells. These cells are found only in the skin and play paramount roles in the innate and adaptive systems. In particular, keratinocytes are antigen-presenting cells that produce chemokines for the recruitment and activation of leukocytes (innate immune response), leading to the activation of the adaptive immune system. Langerhans cells, found in the top layer of the epidermis, detect foreign elements and alert other cells to activate immune function.

[0006] Any cell depletion, immune malregulation or dysfunction may favor the appearance of findings such as non-pathological changes in the visual and / or mechanical properties of the skin, skin discomfort, skin pathological disorders, and hypersensitivity to microbial aggressions. Cutaneous immune disorders are normal physiological phenomena that appear with age, but may be accelerated by microbial infections (viruses and bacteria), physical or chemical stress, natural aging, UV rays, urban living conditions, etc. The accumulation of factors such as stress, poor diet, environmental, chemical or physical aggressors including sunlight, pollution, dryness or heat may weaken the capacity of these protective cells.

[0007] Antimicrobial peptides (AMPs), also called host defense peptides (HDPs), are part of the innate immune response found in all classes of organisms. Numerous AMPs have been identified in keratinocytes, including psoriasin (S100A7), kebnericin (S100A7A), lactotransferrin (LTF), calcium-binding protein (S100B), human β-defensin (HBD), and cathelicidin (LL-37). In addition to antimicrobial activity, they play a role in the migration of granulocytes, dendritic cells, and T lymphocytes, and in the activation of innate and adaptive immune responses.

[0008] Stimulation of antimicrobial peptides in keratinocytes should make it possible to enhance and / or restore the natural defenses in healthy or diseased skin, thus advantageously recruiting the passive defense system of the skin constituted by the stratum corneum (keratinocytes + intercellular cement) and priming an adaptive immune response in newborns, children, adults and the elderly, whether healthy or not.

[0009] Active ingredients acting on the production of these AMPs enhance the skin's natural defenses and in particular the typical innate immune response of the skin to combat physical, chemical and microbial insults. [Prior art documents] [Non-patent literature]

[0010] [Non-Patent Document 1] Oliveira FA et al., Planta Med 2004;70:780-782 [Non-Patent Document 2] Oliveira FA et al. J Ethnopharmacol 2005;98:103-108 [Non-Patent Document 3] CTFA (Cosmetic Ingredient Handbook), 16th edition (2016)) [Non-Patent Document 4] Gleize, B., M. Steib, M. Andre, and E. Reboul.2012.Simple and fast HPLC method for simultaneous determination of retinol, tocopherols, coenzyme Q10 and carotenoids in complex samples.Food Chemistry134:2560~2564 [Non-Patent Document 5] Bauer, S., E. Schulte, and H.-P. Thier. 2004. Composition of the surface wax from tomatoes:I. Identification of the components by GC / MS. European Food Research and Technology 219 [Non-Patent Document 6] Johannes Karl Fink's book "Reactive Polymers Fundamentals and Applications (2nd Edition)" (Plastics Design Library: 2013), p.303-315, Chapter 12 "Terpene Resins", 535p. Summary of the Invention [Problem to be solved by the invention]

[0011] There is therefore a need for new active ingredients that stimulate antimicrobial peptide production in keratinocytes. [Means for solving the problem]

[0012] The present invention relates to the cosmetic use of a peel extract of Solanum lycopersicon fruit for maintaining, balancing or strengthening the natural defenses of the skin or mucous membranes.

[0013] In some embodiments, the lipophilic Solanum lycopersicon fruit peel extract is depleted in lycopene.

[0014] The cosmetic use of the present invention is preferably for strengthening the skin barrier function and / or for maintaining or increasing the resistance or tolerance of the skin to external insults or stresses, such as chemical, physical or microbial insults, and / or for preventing or treating non-pathological changes in the skin caused by insults or stresses, such as chemical, physical or microbial insults.

[0015] In some embodiments, the lipophilic Solanum lycopersicon fruit peel extract is used as a soothing agent, particularly for improving or restoring skin comfort and / or for restoring and / or maintaining a healthy skin microbiome.

[0016] In a particular embodiment, the lipophilic Solanum lycopersicon fruit peel extract is preferably used in combination with a vegetable oil or mineral oil, preferably a vegetable oil. The mass ratio of the lipophilic Solanum lycopersicon fruit peel extract to the vegetable oil or mineral oil is preferably 1:2 to 1:70. The vegetable oil and the lipophilic Solanum lycopersicon fruit peel extract can be obtained by simultaneous or separate extraction of tomato by-products, for example by supercritical CO2 extraction.

[0017] According to the invention, the lipophilic Solanum lycopersicon fruit peel extract advantageously contains up to 0.5% by weight, preferably up to 0.3% by weight, preferably up to 0.2% by weight, preferably up to 0.1% by weight of lycopene relative to the total weight of the extract.

[0018] The lipophilic Solanum lycopersicon fruit peel extract preferably contains at least 5% by weight of amyrins, in particular α-amyrin, β-amyrin and / or δ-amyrin, relative to the total weight of the extract, and more preferably the lipophilic Solanum lycopersicon fruit peel extract contains at least 1.5% by weight of α-amyrin, at least 1% by weight of β-amyrin and at least 2.5% by weight of δ-amyrin, relative to the total weight of the extract.

[0019] The lipophilic Solanum lycopersicon fruit peel extract advantageously further comprises at least 1.5% by weight of sterols relative to the total weight of the extract, and preferably at least 1% by weight of β-sitosterol and stigmasterol relative to the total weight of the extract.

[0020] In some embodiments, the lipophilic Solanum lycopersicon fruit peel extract is present in a cosmetic composition for topical administration in a mass content of 0.01% to 30%, in particular 0.1% to 5%, relative to the total mass of the composition, said composition comprising at least one cosmetically acceptable excipient.

[0021] In some embodiments, the lipophilic Solanum lycopersicon fruit peel extract, the combination of lipophilic Solanum lycopersicon fruit peel extract and vegetable oil, or the cosmetic composition is topically applied or orally administered to healthy subjects having sensitive skin, dry skin, aging skin, skin prone to freckles, skin prone to acne, skin prone to atopy, or skin weakened by external aggression or stress.

[0022] The present invention also relates to an oral or topical composition, preferably comprising as active ingredient a lipophilic Solanum lycopersicon fruit peel extract, depleted in lycopene, as defined above, for use in the treatment of acne-prone, freckle-prone and / or atopic skin.

[0023] The present invention also relates to an oral or topical composition comprising as active ingredient a lipophilic peel extract of Solanum lycopersicon fruit, preferably depleted in lycopene, as defined above, for use in the treatment of skin diseases characterized by an altered or imbalanced innate immune response, preferably selected from eczema, psoriasis, rosacea, acne, dermatitis, atopic dermatitis and irritated skin.

[0024] The present invention also relates to a lipophilic Solanum lycopersicon fruit peel extract: maximum 0.3% by weight, preferably maximum 0.2% by weight, preferably maximum 0.1% by weight, of lycopene relative to the total weight of the extract; - at least 5% by weight of amyrins, in particular α-amyrin, β-amyrin and / or δ-amyrin, relative to the total weight of the extract; at least 1.5% by weight of sterols, relative to the total weight of the extract; preferably at least 1% by weight of β-sitosterol and stigmasterol, relative to the total weight of the extract.

[0025] The present invention also relates to a cosmetic composition comprising a lipophilic Solanum lycopersicon fruit peel extract as defined above, preferably in a mass content ranging from 0.01% to 30% relative to the total mass of the composition, and at least one cosmetically acceptable excipient. [Brief description of the drawings]

[0026] [Figure 1] FIG. 1 is a graph showing the change in erythema level over time depending on the test product: placebo composition or 1% or 2% of the extract of the present invention. [Diagram 2] 2A-2B are graphs showing the change in hydration over time depending on the test products: placebo composition or the extract of the invention at 1% (FIG. 2A) or 0.5% (FIG. 2B). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] The inventors have found that the lipophilic Solanum lycopersicon fruit peel extract can be used to enhance the skin's natural defenses, in particular the skin's innate immunity, for example through antimicrobial peptide production.

[0028] As demonstrated in the experimental section, the lipophilic Solanum lycopersicon fruit peel extract used according to the present invention provides transcriptional regulation, e.g. modulating gene expression profiles in ex vivo human skin explants.

[0029] Notably, the lipophilic Solanum lycopersicon fruit peel extract of the present invention upregulates the expression of genes encoding antimicrobial peptides (AMPs), such as psoriasin (S100A7), koebnerisin (S100A7A), lactotransferrin (LTF), and calcium binding protein (S100B). Such upregulation of AMP genes was observed both under basal and stimulated oxidative conditions (i.e., in the presence of phorbol 12-myristate 13-acetate).

[0030] Therefore, the lipophilic Solanum lycopersicon fruit peel extract is expected to stimulate innate immunity in the skin in vivo, and consequently strengthen the protective skin barrier. The Solanum lycopersicon fruit peel extract used in the experimental section is generally depleted of lycopene, but contains significant amounts of amyrins, especially δ-amyrin, and sterols.

[0031] Of note, amyrins are a class of pentacyclic triterpenes that are ubiquitously distributed in the plant kingdom. α-amyrin (ursane skeleton), β-amyrin (oleanane skeleton) and δ-amyrin are three closely related natural compounds of triterpenes. ABAM (α and β-amyrin) have been shown to exhibit various pharmacological activities, such as gastroprotective activity (Oliveira FA et al., Planta Med 2004; 70: 780-782) and hepatoprotective activity (Oliveira FA et al., J Ethnopharmacol 2005; 98: 103-108). On the other hand, δ-amyrin is not ubiquitously distributed in plants.

[0032] To the best of our knowledge, it has not been described in the prior art that a Solanum lycopersicon fruit extract, which is rich in amylins and depleted in lycopene, promotes innate immunity in the skin, particularly by inducing the expression of AMPs.

[0033] The present invention therefore relates to the cosmetic and non-therapeutic use of a peel extract of Solanum lycopersicon fruit for maintaining, balancing or strengthening the natural defenses of the skin or mucous membranes.

[0034] In the context of the present invention, "Solanum lycopersicon fruit" or "tomato" refers to the edible berry of the plant Solanum lycopersicon, commonly known as the tomato plant. The terms "tomato" and "Solanum lycopersicon fruit" can be used interchangeably.

[0035] In the context of the present invention, the term "Solanum lycopersicon fruit peel" refers to the outer protective layer of tomato. Solanum lycopersicon fruit peel comprises an epidermis covered with a cuticle (cuticular membrane) and a multi-layered hypodermis. The terms "Solanum lycopersicon pericarp", "Solanum lycopersicon fruit peel", "tomato fruit peel" and "tomato pericarp" can be used synonymously. Thus, the term "tomato peel extract" or "Solanum lycopersicon fruit peel extract" refers to a lipophilic extract of tomato peel as defined herein.

[0036] In the context of the present invention, the term "skin" refers to any part of the skin of the human body, in particular the skin of the face, including the lips and eyelids, the neck, the scalp, and the skin of the hands. The term "skin" may also include skin appendages such as hair and nails.

[0037] The skin's natural defense system protects the skin from chemical, physical or microbial insults, with two main objectives: to block the insult and to warn the remaining immune system of the insult. By maintaining, balancing (or normalizing) or strengthening the natural defenses of the skin or mucous membranes, the skin and the skin microbiome are kept in good health. Thus, the skin is able to adequately defend against chemical, physical or microbial insults while maintaining its visual aspects and its mechanical properties.

[0038] In the context of the present invention, the terms "invasion" or "stress" refer to any exposure of the skin to an external condition that can alter or induce an immune response of the skin. These terms may also refer to internal or emotional stress that can alter or induce an immune response of the skin.

[0039] In the context of the present invention, chemical insults include insults by allergens, pollutants (e.g. exhaust fumes, particulates, volatile organic compounds), tobacco, irritants such as organic solvents, drying agents, acidic or basic solutions, etc., and certain therapeutic agents such as disinfectants, hydroalcoholic solutions or gels, anti-acne agents.

[0040] In the context of the present invention, physical aggression includes thermal aggression, mechanical aggression (e.g. peeling, dermo-abrasion, shaving, hair removal, laser) and electrical aggression. In certain embodiments, physical aggression refers to weather conditions such as wind, cold, or heat.

[0041] In the context of the present invention, microbial insults include insults by bacteria, fungi, viruses and other pathogenic agents.

[0042] In certain embodiments, the insult further includes stress caused by lifestyle, such as tobacco consumption, alcohol consumption, a high-fat or poor quality diet, consumption of ultra-processed foods, emotional stress, and the like.

[0043] In certain embodiments, the insult does not include insult with UV radiation.

[0044] In particular, the peel extract of the fruit of Solanum lycopersicon used according to the invention enhances the production of antimicrobial peptides by keratinocytes of the skin and therefore enhances the innate immune response of the skin.

[0045] Thus, the present invention may relate to the cosmetic use of a peel extract of Solanum lycopersicon fruit for maintaining, balancing or enhancing the innate immune response of the skin or mucous membranes. The present invention may also relate to the cosmetic use of a peel extract of Solanum lycopersicon fruit for contributing to the normal functioning of the immune system, in particular the skin immune system, and / or for boosting the innate immunity of the skin. The cosmetic use of a peel extract of Solanum lycopersicon fruit may also be for restoring immune imbalances of the skin.

[0046] Thus, in a particular embodiment, the peel extract of Solanum lycopersicon fruit is used in the cosmetic field to strengthen the barrier function of the skin and / or to maintain or increase the resistance or tolerance of the skin against external insults or stresses, such as chemical, physical or microbial insults.

[0047] In the context of the cosmetic use of the present invention, the Solanum lycopersicon fruit peel extract may be applied topically to healthy areas of the skin or may be administered orally to subjects with healthy skin.

[0048] As used herein, "healthy skin" or "healthy skin area" refers to skin that is not afflicted with any skin disease or wound. However, the term "healthy skin" also encompasses skin that exhibits a non-pathological, altered, immune response to external insults or stresses, and / or non-pathological changes in the visual aspects or mechanical properties of the skin, as further described below.

[0049] In some embodiments, the Solanum lycopersicon fruit peel extract is administered to a subject having sensitive skin, dry skin, aging skin, freckle-prone skin, acne-prone skin, atopic skin, or skin that has been weakened by external aggression or stress, such as chemical, physical, or microbial aggression.

[0050] By increasing the skin's resistance to external aggressions, Solanum lycopersicon fruit peel extract can prevent or alleviate non-pathological changes in the skin caused by exposure to external aggressions.

[0051] The present invention therefore also relates to the use of a peel extract of the fruit of Solanum lycopersicon for preventing or treating non-pathological changes in the skin caused by insults or stress, for example as described above.

[0052] As used herein, non-pathological changes in the skin refer to non-pathological alterations in the appearance or mechanical properties of the skin, including, but not limited to, thinning of the skin, particularly the epidermis, loss of skin radiance, dark circles, dullness of the face, loss of skin elasticity, changes in skin smoothness, increased roughness with redness, dryness, etc.

[0053] Within the scope of the present invention, "preventing non-pathological changes" refers to the fact of preventing, slowing down or delaying the occurrence of said skin changes.

[0054] By "treating a non-pathological change" is meant correcting, attenuating, diminishing, making less noticeable, reducing the appearance, or even eliminating a skin change.

[0055] In a further embodiment, the present invention relates to the cosmetic use of a peel extract of Solanum lycopersicon fruit, preferably depleted in lycopene, for maintaining, restoring or balancing the skin microbiota.

[0056] As used herein, the terms "skin microbiota", "skin microbiome" or "skin flora" refer to microorganisms present on the skin, typically human skin, and include bacteria, mycobacteria, viruses, fungi and parasitic bacteria. Most are found in the superficial layers of the epidermis and above the hair follicles. Skin flora is usually non-pathogenic and either commensal or mutualistic. Benefits that such microorganisms may confer include preventing transient pathogenic microorganisms from colonizing the skin surface by competing for nutrients, secreting chemicals against pathogenic microorganisms, or stimulating the skin's immune system.

[0057] "Restoring" or "balancing" or "normalizing" the skin microbiota means restoring microbial diversity to promote skin health and / or obtain a balance of microbial distribution corresponding to healthy skin. For example, a peel extract of Solanum lycopersicon fruit may be able to reduce the abundance of species that may be involved in freckles or acne, such as certain strains of C. acnes. In view of such circumstances, a peel extract of Solanum lycopersicon fruit may typically be used in subjects with acne-prone or freckle-prone skin.

[0058] We further showed that the peel extract of Solanum lycopersicon fruit modulates the expression of genes involved in inflammation and oxidative stress under both basal and stimulated conditions.

[0059] Indeed, the peel extract of Solanum lycopersicon fruit induced a strong downregulation of genes involved in inflammation (mainly CXCL8, IL6, CXCL2, CXCL3, CCL20, TNFAIP3, TNFAIP6), oxidative stress (PTGS2, GPX3, HMOX1), and terminal keratinocyte differentiation (KRT17, SPRR1A, TGM1, several LCEs, EREGs, CDSN, and IVL).

[0060] Such down-regulation may also contribute to maintaining and strengthening normal skin barrier function, for example by preventing over-reaction of the skin to external insults or stress.

[0061] Furthermore, the peel extract of the fruit of Solanum lycopersicon according to the invention can further be used to suppress inflammation when the skin is under oxidative stress and reactive oxygen species are produced.More generally, the peel extract of the fruit of Solanum lycopersicon can exhibit a soothing effect, for example, via the suppression of oxidative stress and anti-inflammatory effects.

[0062] Thus, in a further embodiment, the peel extract of Solanum lycopersicon fruit is used in particular as a soothing agent for improving or restoring skin comfort as well as for preventing or relieving skin discomfort.

[0063] As used herein, the term "skin discomfort" refers to a range of unpleasant sensations not associated with a pathological condition, such as tightness, stinging, itching, or heating, dry or dehydrated skin, and temporary redness. These sensations are not associated with a pathological condition and may be induced by certain external factors (e.g., prolonged exposure to sunlight, wind, or cold), by certain cosmetic treatments (e.g., by washing too frequently with lime water or hydroalcoholic solutions, by aggressive cosmetic treatments, such as peeling, shaving, exfoliation, hair removal, coloring, permanents, etc.), or may be associated with so-called sensitive, irritable, reactive, intolerant, or atopic skin.

[0064] For example, Solanum lycopersicon fruit peel extract can be used to relieve, or more generally manage, sensitive, reactive or intolerant skin.

[0065] The term "sensitive, reactive or intolerant skin" refers to skin characterized by a disproportionate reaction to external factors that cause discomfort to the skin. This increased reactivity can result from non-pathological alterations of the barrier function of the skin, or more generally of the skin's innate immune system, lowering the skin's tolerance threshold to external stimuli.

[0066] More specifically, the peel extract of Solanum lycopersicon fruit may also be used as a soothing agent in the skin by controlling the skin response to oxidative stress and / or by controlling inflammatory skin responses.

[0067] In a more general aspect, the present invention may also relate to a method for the cosmetic treatment of sensitive skin, dry skin, dehydrated skin, intolerant skin, aged skin, freckle-prone skin, acne-prone skin, atopic skin, skin weakened by external aggressions or stresses, such as chemical, physical or microbial aggressions, skin exhibiting a non-pathological immunological imbalance or a non-pathological reddening, characterized in that the method comprises applying to the skin and / or mucous membranes or administering orally a peel extract of the fruit of Solanum lycopersicon as defined herein.

[0068] The present invention may also relate to a method for the cosmetic care of the skin and / or mucous membranes, comprising the step of topically applying or orally administering to a subject a peel extract of the fruit of Solanum lycopersicon as defined in the present specification, with a view to improving the condition and / or appearance of the skin and / or mucous membranes.

[0069] In the context of the present invention, the term "improving the condition and / or appearance of the skin" includes: - Keep skin tones consistent; - balancing skin tone and / or restoring a more radiant and / or brighter and / or clearer complexion; - balancing the epidermis, in particular the facial skin, and / or restoring firmness and / or promoting firming and anti-ageing of the epidermis; - balancing and / or moisturising the skin, especially the facial skin; - Preventing or treating dull and / or dull skin tones; - Preventing or treating uneven skin tone, including pigmentation spots induced by external aggressions or stress; - Promoting a youthful and radiant appearance to the skin, especially the facial skin; - Softening the appearance of the skin. - promoting or accelerating the healing of the epidermis, especially of the face; - Rejuvenating the skin, especially of the face; - Increasing the thickness of the epidermis; - Balancing and / or promoting a healthy complexion, and / or - Preventing, treating or restoring the barrier function of the skin.

[0070] In a further embodiment, the peel extract of Solanum lycopersicon fruit is used as an immunity skin boost agent and / or skin protectant by controlling the skin response to oxidative stress and enhancing antimicrobial peptide production by skin keratinocytes.

[0071] In the cosmetic methods and uses described above, the peel extract of Solanum lycopersicon fruit is preferably used as a cosmetic agent, i.e. as an active agent with cosmetic effect. By "active agent with cosmetic effect" is meant a compound having an action on the skin that brings about at least one cosmetic effect on the skin. By "cosmetic effect" is meant any non-therapeutic effect that aims to modify and / or improve the aspect, mechanical properties or feel of the skin or mucous membranes and / or to protect them against non-pathological changes of the skin caused by external insults.

[0072] The present invention also relates to an oral or topical composition, preferably comprising as active ingredient a lipophilic Solanum lycopersicon fruit peel extract, depleted in lycopene, as defined above, for use in the treatment of acne-prone, freckle-prone and / or atopic skin.

[0073] The present invention further relates to an oral or topical composition comprising as active ingredient a peel extract of Solanum lycopersicon fruit, advantageously depleted in lycopene, preferably as defined herein, for use in the treatment of skin diseases characterized by an alteration or imbalance of the innate immune system, preferably selected from eczema, psoriasis, rosacea, acne, dermatitis, atopic dermatitis and irritated skin.

[0074] The present invention further relates to the use of a peel extract of the fruit of Solanum lycopersicon, advantageously depleted in lycopene, preferably as defined herein, for the production of a pharmaceutical or dermatological composition for the treatment of a skin disease characterized by an alteration or imbalance of the innate immune system, preferably selected from eczema, psoriasis, rosacea, acne, dermatitis, atopic dermatitis and irritated skin.

[0075] The present invention further relates to a method for treating a skin disease characterized by an alteration or imbalance of the innate immune system, preferably selected from eczema, psoriasis, rosacea, acne, dermatitis, atopic dermatitis and irritated skin, comprising administering, in particular topically or orally, to a subject in need thereof, an effective amount of an extract of the skin of Solanum lycopersicon fruits, advantageously depleted in lycopene, preferably as defined herein.

[0076] In a further embodiment, the peel extract of Solanum lycopersicon fruit defined herein may be for use to prevent or treat disorders or diseases of the skin and / or mucous membranes, whether immature, normal or mature / senescent.

[0077] In a further embodiment, the present invention may relate to the use of a peel extract of Solanum lycopersicon fruits as defined herein for producing a pharmaceutical or dermatological composition for preventing or treating disorders or diseases of the skin and / or mucous membranes, whether immature, normal or mature / aged.

[0078] In a further embodiment, the present invention may relate to a method for preventing or treating disorders or diseases of the skin and / or mucous membranes, whether immature, normal or mature / aged, preferably comprising the step of administering, in particular topically or orally, to a subject in need thereof an effective amount of a peel extract of Solanum lycopersicon fruit, advantageously depleted in lycopene, as defined herein.

[0079] In the above mentioned embodiments, the skin and / or mucous membrane disorders or diseases may be selected from the group consisting of inflammatory disorders, oxidative disorders, age spots, disorders related to radical attack associated with chemical or air pollution and / or associated with exposure to UV or IR radiation, barrier or homeostasis disorders, ageing, in particular natural ageing and / or actinic ageing, and / or physical, chemical or microbial aggressors, more preferably inflammatory and irritant disorders, or barrier or homeostasis disorders.

[0080] Advantageously, the inflammatory or irritant diseases of the skin or the barrier or homeostasis disorders of the skin are acne, rosacea or erythrocouperose, vascular disorders, in particular age spots, seat dermatitis, atopic dermatitis, eczema, contact dermatitis, irritant dermatitis, allergic dermatitis, seborrheic dermatitis (cradle cap), xerosis, erythema of the skin, old or photoaged skin, photosensitive skin, pigmented skin (liver spots, post-inflammatory hyperpigmentation, etc.), skin with stretch marks, sunburn, irritation due to chemical, physical, bacteriological and fungal agents, disorders due to radical attack linked to chemical or air pollution and / or exposure to UV or IR radiation.

[0081] Combination of Solanum lycopersicon fruit peel extract and vegetable oil In an advantageous embodiment of the invention, the peel extract of Solanum lycopersicon fruit is used in combination with a lipophilic vehicle, preferably a vegetable oil or a mineral oil, more preferably a vegetable oil, in particular the peel extract of Solanum lycopersicon fruit is diluted in a vegetable oil.

[0082] The inventors have found that by combining the peel extract of Solanum lycopersicon fruit used according to the invention with a lipophilic vehicle, such as vegetable oil, the compounds of particular interest for use according to the invention, including amyrins and sterols, have a higher bioaccessibility. Thus, the cosmetic, dermatological or pharmaceutical activity of the peel extract of Solanum lycopersicon fruit is enhanced when said extract is diluted in a lipophilic vehicle, such as vegetable oil.

[0083] Advantageously, the lipophilic vehicle is a vegetable oil.

[0084] Advantageously, the vegetable oil used according to the invention is an oil selected from the group consisting of tomato seed oil, apple seed oil, pear seed oil, sunflower oil, palm oil, palm kernel oil, coconut oil, grape seed oil, black mustard oil, poppy seed oil, karite butter oil, sweet almond oil, soybean oil, avocado oil, groundnut oil, cottonseed oil, sesame oil, olive oil, corn oil, cocoa bean oil, castor oil, behen oil, flax oil, rapeseed oil, annatto oil, wheat germ oil, safflower oil, walnut oil, hazelnut oil and turnip seed oil. Preferably, the vegetable oil used according to the invention is a vegetable seed oil, more preferably tomato seed oil.

[0085] In a particular embodiment, the mass ratio of Solanum lycopersicon fruit peel extract to vegetable oil or mineral oil, preferably vegetable oil, is 1:70 to 1:1, such as 1:50 to 9:10, for example, 0.1 to 0.9, for example, 0.2 to 0.8 or 0.3 to 0.6, for example, 1:2 (0.5).

[0086] For example, the peel extract of Solanum lycopersicon fruit can be combined with a lipophilic vehicle, preferably tomato seed oil, to obtain an intermediate composition having a weight ratio of Solanum lycopersicon fruit peel extract to lipophilic vehicle of 0.1 to 0.9, for example about 0.5. This intermediate composition is preferably incorporated into a cosmetic composition and applied to the skin. For example, such an intermediate composition can represent 0.1% to 10% by weight of the total weight of the cosmetic composition applied to the skin.

[0087] As another example, the peel extract of Solanum lycopersicon fruit may be diluted in a lipophilic vehicle in a weight ratio of Solanum lycopersicon fruit peel extract to vegetable or mineral oil of 1:75 to 1:20, in particular 1:60 to 1:30, preferably 1:55 to 1:45, such as about 1:49, etc. In such an embodiment, the combination may be applied directly to the skin or administered by oral route.

[0088] In a particular embodiment, the vegetable oil used according to the present invention is tomato seed oil, which preferably contains at least 40% by weight, particularly 45% to 70% by weight, of linoleic acid relative to the total weight of the tomato seed oil. The tomato seed oil used according to the present invention may further contain at least 10% by weight, particularly 10% to 30% by weight, of oleic acid relative to the total weight of the tomato seed oil. The tomato seed oil used according to the present invention may further contain at least 5% by weight, particularly 5% to 15% by weight, of oleic acid relative to the total weight of the tomato seed oil. For example, the vegetable oil may contain 45% to 55% by weight of linoleic acid, 15% to 25% by weight of oleic acid, and 5% to 15% by weight of palmitic acid.

[0089] Compositions Comprising Solanum Lycopersicon Fruit Peel Extract or Combinations of Said Extract with Vegetable Oils Solanum lycopersicon fruit peel extract is usually administered topically or orally in the form of a composition.

[0090] According to the present invention, the peel extract of Solanum lycopersicon fruit can be used by itself, in combination with a vegetable oil or mineral oil, or can be present as an active ingredient in a cosmetic, dermocosmetic, pharmaceutical, or nutraceutical composition, such as a nutraceutical, preferably a cosmetic, dermocosmetic, or nutraceutical composition. When the peel extract of Solanum lycopersicon fruit is combined with a vegetable oil or mineral oil, the combination can also be present in a cosmetic, dermocosmetic, pharmaceutical, or nutraceutical composition, such as a nutraceutical, preferably a cosmetic, dermocosmetic, or nutraceutical composition.

[0091] The compositions according to the invention are preferably formulated for topical or oral administration, especially for topical administration.

[0092] Advantageously, the extract of peel of the fruit of Solanum lycopersicon is present in the composition in a mass content ranging from 0.001% to 20%, from 0.01% to 10%, in particular from 0.1% to 5% relative to the total mass of the composition, said composition comprising at least one excipient.

[0093] Depending on its type (cosmetic, pharmaceutical or dermatological), the composition according to the invention further comprises at least one cosmetically acceptable, pharma- ceutical, nutraceutical or dermatologically acceptable excipient. In particular, the composition according to the invention may further comprise at least one excipient known to the skilled person cosmetically, pharmaceutical, nutritionally or dermatologically, selected from among surfactants and / or emulsifiers, thickeners, preservatives, chemical or mineral filters, hydrating agents, buffers, chelating agents, denaturants, opacifying agents, pH adjusters, reducing agents, stabilizing agents, hot water, gelling agents, film-forming polymers, fillers, mattifying agents, gloss agents, pigments, dyes, fragrances and mixtures thereof. The skilled person will know how to adapt the formulation of the composition according to the invention by using his general knowledge. The CTFA (Cosmetic Ingredient Handbook, 16th Edition (2016)) also describes various cosmetic excipients suitable for use in the present invention.

[0094] The compositions according to the invention can be formulated in different formulations adapted for topical administration, including creams, emulsions, microemulsions, nanoemulsions, serums, soaps, gels, milks, ointments, lotions, oils, aqueous, alcoholic or glycolic solutions, powders, patches, sprays, shampoos, varnishes, foams or any other products for external application.

[0095] In fact, the composition according to the invention may be in the form of any type of cosmetic preparation, such as, for example, a beauty care product, a make-up product or a personal hygiene product.

[0096] The compositions according to the invention can also be formulated in different formulations adapted for oral administration, including tablets, capsules, coated tablets, syrups, suspensions, liquids, powders, pellets, emulsions, suspensions of microspheres or nanospheres, lipid vesicle suspensions or various polymer-based vesicles.

[0097] Advantageously, the composition is a topical cosmetic composition.

[0098] The cosmetic composition may also contain other cosmetic active ingredients. Many cosmetic active ingredients are known to those skilled in the art to improve the health and / or physical appearance of the skin. On the other hand, the compounds described in the present invention may have synergistic effects when combined with each other. These combinations are also subject to the present invention. The CTFA Cosmetic Ingredient Handbook, 16th Edition (2016), describes various cosmetic and pharmaceutical ingredients commonly used in the cosmetic and pharmaceutical industries, which are particularly suitable for topical use. Examples of these classes of ingredients include, but are not limited to, the following ingredients: abrasives, absorbents, cosmetic compounds such as fragrances, pigments, dyes, and the like, essential oils, astringents such as olive oil, cloves, menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazel distillate, anti-acne agents, anti-flocculating agents, anti-foaming agents, antimicrobial agents (e.g., iodopropyl butylcarbamate), antioxidants, binders, biological additives, buffers, foaming agents, chelating agents, additives, biocidal agents, denaturants, thickeners, and vitamins and derivatives or equivalents thereof, film-forming materials, polymers, opacifying agents, pH adjusters, reducing agents, decolorizing or brightening agents (e.g., hydroquinone, kojic acid, ascorbic acid, magnesium ascorbyl phosphate, ascorbyl glucosamine, ascorbyl phosphate ... glucosamine), and conditioning agents (e.g., moisturizers, etc.).

[0099] Advantageously, the peel extract of Solanum lycopersicon fruit used according to the invention, alone or in combination with a lipophilic vehicle, such as a vegetable oil or a mineral oil, is the sole active ingredient of the composition.

[0100] In a particular embodiment, the composition used in accordance with the present invention comprises - Solanum lycopersicon fruit peel extract at 0.001%-20%, particularly 0.01%-10%, more particularly 0.1%-5%; - 60% to 99.999% of at least one excipient; and - may contain from 0% to 20% of additional active ingredients (expressed as the mass content relative to the total mass of the composition);

[0101] The dosage and optimal galenical formulation according to the invention can be established according to the criteria usually taken into account when prescribing a suitable pharmacological, dermatological, nutraceutical or cosmetic treatment for a patient or animal, such as the age and weight of the patient or animal, the severity of the general condition, the tolerance of the treatment, the observed side effects, the skin type.

[0102] Solanum lycopersicon fruit peel extract and method for obtaining same The Solanum lycopersicon fruit peel extract according to the present invention is a lipophilic Solanum lycopersicon fruit peel extract obtained from the extraction of Solanum lycopersicon fruit peel, in particular from tomato by-products derived from industrial or food waste. The tomato by-product from which the extract is obtained is usually tomato pomace from the food industry. If the tomato by-product contains tomato skin and seeds, the seeds and skin can be separated, for example by screening, and the skin is recovered.

[0103] The Solanum lycopersicon fruit peel extract according to the present invention is a lipophilic Solanum lycopersicon fruit peel extract. The Solanum lycopersicon fruit peel extract according to the present invention is less soluble in water compared to lipid media, e.g. vegetable oils. The Solanum lycopersicon fruit peel extract according to the present invention is preferably Solanum lycopersicon fruit peel wax, also called Solanum lycopersicon fruit (tomato) skin wax. The Solanum lycopersicon fruit peel extract according to the present invention is preferably depleted of lycopene and preferably contains amyrins and sterols.

[0104] In a preferred embodiment of the invention, the peel extract of Solanum lycopersicon fruits used is depleted of lycopene. Advantageously, the extract contains up to 0.5% by weight, preferably up to 0.3% by weight, preferably up to 0.2% by weight, preferably up to 0.1% by weight, more preferably up to 0.05% by weight of lycopene relative to the total weight of the extract. In particular, the peel extract of Solanum lycopersicon fruits used contains between 0% and 0.1% by weight, preferably between 0% and 0.05% by weight of lycopene relative to the total weight of the extract.

[0105] Lycopene is a carotenoid. In a particular embodiment of the invention, the peel extract of Solanum lycopersicon fruit is depleted of carotenoids. More particularly, the extract comprises up to 0.6% by weight, preferably up to 0.3% by weight, in particular up to 0.2% by weight of carotenoids relative to the total weight of the extract. In the context of the present invention, the mass content of carotenoids, in particular lycopene, is determined by HPLC-DAD according to methods known to the skilled artisan, for example the method described by Gleize et al. (Gleize, B., M. Steib, M. Andre, and E. Reboul. 2012. Simple and fast HPLC method for simultaneous determination of retinol, tocopherols, coenzyme Q10 and carotenoids in complex samples. Food Chemistry Vol. 134: 2560-2564). In the context of the present invention, "up to X%" means 0% to X%.

[0106] In a preferred embodiment, the peel extract of Solanum lycopersicon fruit used according to the invention is rich in amyrins, in particular delta-amyrin. In particular, the peel extract of Solanum lycopersicon fruit used according to the invention contains at least 5% by weight of amyrins, based on the total weight of the peel extract of Solanum lycopersicon fruit. Advantageously, the peel extract of Solanum lycopersicon fruit used according to the invention contains 5% to 32% by weight of amyrins, based on the total weight of the peel extract of Solanum lycopersicon fruit. For example, the peel extract of Solanum lycopersicon fruit used according to the invention contains 5% to 25% by weight, 5% to 20% by weight, 5% to 15% by weight, or 5% to 10% by weight of amyrins, based on the total weight of the peel extract of Solanum lycopersicon fruit.

[0107] Amyrins are triterpene compounds that can be found in the forms of α-amyrin, β-amyrin and δ-amyrin of the following formulae (Iα), (Iβ) and (Iδ).

[0108] [ka]

[0109] According to the present invention, the peel extract of Solanum lycopersicon fruit used preferably contains α-amyrin, β-amyrin and / or δ-amyrin, more preferably the peel extract of Solanum lycopersicon fruit used contains α-amyrin, β-amyrin and δ-amyrin, in particular the peel extract of Solanum lycopersicon fruit contains at least 1.5% by weight, in particular 1.5% to 10% by weight, of α-amyrin, at least 1% by weight, in particular 1% to 7% by weight, of β-amyrin and at least 2.5% by weight, in particular 2.5% to 17% by weight, of δ-amyrin, relative to the total weight of the peel extract of Solanum lycopersicon fruit. In the context of the present invention, the mass content of amylins is determined by methods known to those skilled in the art, for example by GC-MS according to the method described by Bauer et al. (Bauer, S., E. Schulte, and H.-P. Thier. 2004. Composition of the surface wax from tomatoes: I. Identification of the components by GC / MS. European Food Research and Technology 219).

[0110] In a particular embodiment, the mass ratio of δ-amyrin to the sum of α-amyrin and β-amyrin is 0.8 to 1.2, preferably 0.9 to 1.1.

[0111] The peel extract of Solanum lycopersicon fruit used according to the invention may also be rich in sterols, in particular β-sitosterol and stigmasterol. Preferably, the peel extract of Solanum lycopersicon fruit further comprises at least 1.5% by weight, in particular 1.5% to 12% by weight, of sterols, based on the total weight of the peel extract of Solanum lycopersicon fruit. More preferably, the peel extract of Solanum lycopersicon fruit comprises at least 1% by weight, in particular 1% to 3% by weight, of β-sitosterol and stigmasterol, based on the total weight of the peel extract of Solanum lycopersicon fruit. In the context of the present invention, the mass content of sterols, in particular β-sitosterol and stigmasterol, is determined by GC-MS according to methods known to those skilled in the art, for example the method described by Bauer et al.

[0112] The peel extract of Solanum lycopersicon fruits used according to the invention may also contain at least 10% by weight, in particular 10% to 60% by weight, of triglycerides, based on the total weight of the peel extract of Solanum lycopersicon fruits. In the context of the present invention, the mass content of triglycerides is determined by methods known to those skilled in the art, for example UPLC-DAD-M.

[0113] The peel extract of Solanum lycopersicon fruits (tomato) used according to the invention can also contain at least 10% by weight, in particular 10% to 30% by weight, of alkanes, relative to the total weight of the peel extract of Solanum lycopersicon fruits (tomato). According to the invention, the sum of the content of alkane types C31, C32 and C33 is at least 70% by weight, in particular 70 to 90% by weight, relative to the total alkane content of the peel extract of Solanum lycopersicon fruits (tomato). In the context of the present invention, the mass content of alkanes is determined by GC-MS according to methods known to the skilled person, for example the method described by Bauer et al.

[0114] The peel extract of Solanum lycopersicon fruits used according to the invention may also contain at least 5% by weight, in particular 5% to 15% by weight, of alkadienes, in particular of the C33 and C35 type, relative to the total weight of the peel extract of Solanum lycopersicon fruits. In the context of the present invention, the mass content of alkanes is determined by GC-MS according to methods known to those skilled in the art, for example the method described by Bauer et al.

[0115] According to the present invention, the peel extract of Solanum lycopersicon fruit is prepared by the following steps: a) selecting tomato peel, in particular tomato peel obtained from tomato pomace; b) optionally grinding the tomato fruit peel; c) extracting the tomato fruit peel to obtain a lipophilic extract; d) optionally filtering the resulting extract to recover a lipophilic tomato fruit peel extract; The preparation method can be obtained by the following steps:

[0116] In step a), the tomato pomace obtained from industrial or food waste may contain tomato peel and seeds. Therefore, a further step of separating the tomato peel and seeds can be carried out by means known to the skilled artisan, for example by sieving (for example through a 1 μm mesh). The tomato peel selected in step a) can also be dried to a residual moisture of up to 10%. Drying methods are generally known to the skilled artisan and include, for example, heating in an oven or dryer at a temperature between 40° C. and 90° C. The drying temperature should be selected to avoid degradation of the compounds of interest, such as amyrins and sterols.

[0117] In step b), the tomato peel is optionally ground by methods commonly known to those skilled in the art, including grinding with a knife mill, a cutting mill or a hammer mill.

[0118] The process for the preparation of a tomato peel extract may further comprise a step of depleting lycopene and advantageously carotenoids. This step may be carried out before, during or after extraction step c) by means generally known to those skilled in the art. In particular, lycopene may be removed by physical or chemical methods known to those skilled in the art, such as adsorption / desorption by using resins (i.e. macroporous adsorption resins, type packed columns LX-68, HP20 or equivalent), crystallization, solvent extraction, chromatography, such as countercurrent chromatography (CCC) or centrifugal partition chromatography (CPC), salting out (precipitation methods), filtration methods (diafiltration, microfiltration and / or ultrafiltration or a combination thereof), thermal methods, distillation or CO2 supercritical extraction. If solvent extraction is used to remove lycopene, the solvents used can be selected from acetone, ethyl acetate, diethyl ether, petroleum ether, hexane, heptane, chloroform, and tetrahydrofuran, mixtures with propylene glycol (1,2-propanediol), water and alkalis, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide or ammonium hydroxide, or trisodium phosphate, and mixtures thereof. Any other solvents known to have a Hildebrand solubility parameter (δ) value between 12 and 36, in particular between 14 and 19, can be used (a list of them can be found, for example, in the book "Reactive Polymers Fundamentals and Applications (2nd Edition)" by Johannes Karl Fink (Plastics Design Library: 2013), p. 303-315, chapter 12 "Terpene Resins", p. 535). When lycopene is removed using a heating method, the tomato fruit peel can be heated at a temperature of 60° C. to 110° C. for, for example, 1 hour to 10 hours until the lycopene is removed.

[0119] In step c), the extraction of the tomato peel can be carried out by several methods well known to those skilled in the art, including physical extraction (e.g. hot or cold pressing in a mechanical press or pressing in a twin screw extruder, etc.), chemical extraction with organic solvents (e.g. aliphatic alkanes, alcohols, chlorinated solvents, fluorinated solvents, etc.), preferably non-polar solvents, or extraction with supercritical media, such as carbon dioxide alone and / or in combination with co-solvents such as vegetable oils.

[0120] In step c), if a solvent extraction method is used, the solvent may be selected from the group consisting of acetone, ethyl acetate, diethyl ether, petroleum ether, hexane, heptane, chloroform, and tetrahydrofuran, mixtures with propylene glycol (1,2-propanediol), water, and alkalis such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, or ammonium hydroxide or trisodium phosphate, and mixtures thereof. The mass ratio of tomato peel extract / solvent during solvent extraction may be 1:1 to 1:60, in particular 1:1 to 1:20.

[0121] In a preferred embodiment of the present invention, step c) is carried out using supercritical extraction. The process of supercritical extraction is carried out in a conventional supercritical extraction apparatus consisting of a supercritical fluid tank, a compressor, an extractor, one or more separators, a thermostatization system and several pressure reducing valves. To carry out supercritical extraction, tomato peels are introduced into an extractor and a supercritical fluid, preferably CO2 alone or in combination with a co-solvent, such as ethanol, more preferably CO2 alone, is passed through a bed of solid starting material under pressure and temperature conditions that allow the solubilization of the compounds of interest, particularly amylins and sterols, in the CO2 supercritical fluid. As the CO2 supercritical fluid traverses the bed of starting material, it extracts the soluble components, which then move to a separator, where the desired product is obtained. The CO2 supercritical fluid is depressurized and then discharged. Advantageously, the CO2 supercritical extraction step is carried out at a pressure of 200 bar to 500 bar, preferably 200 bar to 400 bar, more preferably 200 bar to 350 bar, and at a temperature of 40°C to 80°C, preferably 50°C to 80°C, more preferably 60°C to 80°C. Of note, when using low temperatures (e.g., temperatures below 60°C), higher pressures (e.g., pressures of at least 150 bar) may be required. Similarly, when using low pressures (e.g., pressures below 150 bar), higher temperatures (e.g., temperatures of at least 55°C) should be used.

[0122] In step d), the extract obtained after step c) is optionally subjected to filtration by means generally known to those skilled in the art, for example by sieving through a filter (for example a 45 μm porosity filter). This step removes impurities. The tomato peel extract is then recovered.

[0123] In some embodiments, the method for preparing an extract according to the invention can include one or more additional steps to those described above, including, for example, subjecting the starting plant material to washing, freezing and / or thawing.

[0124] The method may also comprise one or more additional purification steps, preferably carried out after step c) or d) and preferably selected from a distillation step, for example molecular or fractional distillation, a precipitation step, a process filtration, an extraction step, in particular a liquid-liquid extraction with a suitable aqueous solution, solid-liquid on a solid support making it possible to capture the compound to be removed.

[0125] In some embodiments, the lipophilic extract obtained after step c) or d) is optionally subjected to a purification step to enrich the extract in amylins and / or sterols and / or to remove certain compounds with low cosmetic activity, such as alkadienes and / or alkanes, etc. The purification step can be carried out by means commonly known to those skilled in the art, including chromatography, in particular centrifugal partition chromatography (CPC) and / or molecular distillation.

[0126] In a particular embodiment of the invention, when tomato peel extract is combined with a vegetable oil as defined herein, the vegetable oil and the tomato peel extract can be obtained by simultaneous or separate extraction, for example physical extraction, chemical extraction or CO2 supercritical extraction. More particularly, when tomato peel extract is combined with tomato seed oil, said extract and said oil can be obtained by simultaneous or separate extraction, for example physical extraction, chemical extraction or CO2 supercritical extraction, preferably CO2 supercritical extraction, of tomato by-products.

[0127] The vegetable oil used according to the present invention can be obtained by means generally known by those skilled in the art. When tomato seed oil is used according to the present invention, the method of preparation of said oil is similar to that described for tomato peel extract. In a particular embodiment, when tomato seed oil is used according to the present invention, the oil can be obtained by CO2 supercritical extraction under the following conditions: pressure 200bar-450bar, preferably 200bar-400bar, more preferably 200bar-300bar, and temperature 50℃-80℃, preferably 50℃-70℃.

[0128] The present invention will be better understood in light of the following examples, which are presented for illustrative purposes only. EXAMPLES

[0129] Example 1 Preparation of tomato peel extract according to the invention - identification and quantification of triterpenes and carotenoids A tomato peel extract (tomato peel wax) according to the present invention was prepared as follows. a) Select the tomato peel from the tomato pomace; b) tomato peels subjected to heat treatment to reduce the moisture content below 10% and to removal of lycopene (lycopene removal monitored by HPLC-DAD analysis); c) grinding the dry mass obtained in step b) using a cutting mill; d) Extracting a tomato peel fraction by using supercritical CO2 gas at 260-300 bar and 60-80°C; e) The resulting extract is filtered through a 45 μm paper filter to remove impurities.

[0130] The quantitative determination of the target compounds in the obtained tomato peel extract is summarized in Table 1.

[0131] [Table 1]

[0132] Example 2 Preparation of a combination of tomato peel extract and tomato seed oil Tomato seed oil was prepared as follows. a) Selecting tomato seeds from industrial waste; b) drying the tomato seeds at a temperature between 60°C and 110°C until the moisture content is less than 12%; c) grinding the dried mass obtained in step b); d) Extracting tomato seed fraction by using supercritical CO2 gas, i.e. - operating the separation under preselected conditions to obtain the desired tomato seed oil: 200-300 bar and 50-70°C; - The carbon dioxide is then sent to a compressor; e) The resulting oil is filtered through a 45 μm paper filter to remove impurities.

[0133] The tomato seed oil was then combined with the tomato peel extract prepared in Example 1 in a tomato peel extract / tomato seed oil weight ratio of 1 / 49.

[0134] Example 3 Effect of tomato peel extract on gene expression in ex vivo human skin explants under basal conditions In this study, the transcriptional effect (modulation of gene expression) of the extract obtained in Example 1, tomato seed oil and the combination obtained in Example 2 (hereafter named Tomato Peel Extract, Tomato Seed Oil and Combination 1 / 49, respectively) was evaluated on ex vivo human skin explants under basal or phorbol 12-myristate 13-acetate (PMA) stimulated conditions. Comparative analysis of the different transcriptome profiles was performed using the Affymetrix GeneAtlas platform and the human "complete transcriptome" U219 chip, which contains 36,000 transcripts and variants.

[0135] Materials and Methods Biological Model - Model: E2002 Abdominoplasty donor skin explant (2cm x 2cm) (44 year old female) - Culture conditions: 37℃, CO25%

[0136] Test samples and combinations (Table 2)

[0137] [Table 2]

[0138] Culture and treatment After abdominal biopsy was performed, adipose tissue was removed and skin explants were cut into 2 cm x 2 cm pieces and incubated in culture medium. Test samples were then applied topically (5 mg / cm) to the surface of the skin explants. 2 ) or not applied (basal control) and the skin explants were pre-incubated for 24 hours. After pre-incubation: - Basic conditions The medium was removed and replaced with fresh medium and topical treatments were renewed. - Stimulus conditions

[0139] The medium was removed and replaced with fresh medium containing 0.3 μg / ml of the inducer PMA, and the topical treatment was renewed.

[0140] The skin explants were then incubated for 48 hours.

[0141] After the incubation period, the explants were washed in phosphate-buffered saline (PBS) solution, and three punches (4 mm diameter) were made on each explant and immediately frozen at -80°C.

[0142] All experimental conditions were performed with n=3.

[0143] Differential expression analysis Samples were homogenized automatically using Precellys / cryolys and replicates were pooled. Total RNA was extracted from each sample using the NucleoSpin® RNA kit (Macherey-Nagel)® according to the supplier's instructions.

[0144] The quantity and quality of total RNA was assessed for all samples using capillary electrophoresis (Bioanalyzer 2100, Agilent technologies). From each RNA, labeled and amplified antisense RNA (aRNA) was obtained using the GeneChip 3'IVT PLUS kit (Affymetrix). For each labeled and amplified aRNA sample, the profile was assessed before and after fragmentation using capillary electrophoresis (Bioanalyzer 2100, Agilent technologies).

[0145] Hybridization of fragmented aRNA to Affymetrix® U219 chips (36,000 transcripts and variants) was performed for 20 hours at 45° C. in a GeneAtlas™ fluidics Affymetrix® Hybridization Station.

[0146] The U219 chips were analyzed using a GeneAtlas™ Imaging Station (Affymetrix® - 2 μm resolution) to generate fluorescence intensity data.

[0147] result For normalized data, a detection threshold in terms of fold change was defined and applied, for useful interpretation, the threshold was defined as follows:

[0148] [Table 3]

[0149] Furthermore, modulation of a probe is considered significant if its p-value is ≦0.05.

[0150] [Table 4A]

[0151] [Table 4B]

[0152] The tested tomato peel extract diluted 1 / 49 (w / v) in tomato seed oil induced significant modulation in gene expression profiles.

[0153] Under basal conditions, when compared to the diluent tomato seed oil, the tomato peel extract tested at a ratio of 1 / 49 (w / v) induced a strong inhibition of genes involved in inflammation (mainly CXCL8, IL6, CXCL2), oxidative stress (PTGS2, GPX3, HMOX1) and terminal keratinocyte differentiation (KRT17, SPRR1A, TGM1, several LCEs, EREG, CDSN). In parallel, the tomato peel extract induced an upregulation of antimicrobial peptides (LTF, S100A7, S100A7A, S100B) and KRT6C and COL3A1 markers.

[0154] Under stimulated conditions, the tested tomato peel extracts diluted 1 / 49 (w / v) in tomato seed oil induced significant modulation in gene expression profile. A slight inhibition of genes involved in immune response (CCL22, SERPINB9, CD83, IDO1, IL20, LIF) and genes involved in matrix degradation (MMP10 and MMP7) was observed under stimulated conditions. Tomato peel extracts also induced an increase in markers involved in terminal keratinocyte differentiation (SPRR2B, CASP14, LCE3D, and LCE3E) and a slight upregulation of markers involved in innate immunity (PI3, S100A7, S100B). When compared to the diluent tomato seed oil, tomato peel extracts induced an inhibition of genes involved in inflammatory response (mainly CXCL8, IL6, CXCL2, CXCL3, SAA1, IL20, TNFAIP3, and TNFAIP6). In parallel, tomato peel extract induced upregulation of antimicrobial peptides (S100A7A) and markers involved in terminal keratinocyte differentiation (SPRR2B, KRT6C, SPRR2A).

[0155] conclusion Under the experimental conditions of this study, the tested tomato peel extract diluted 1 / 49 (w / v) in tomato seed oil showed a clear soothing effect (suppression of oxidative stress) in this ex vivo skin model. The extract also significantly promoted the innate immunity of ex vivo skin through upregulation of antimicrobial peptides.

[0156] Example 4 Effect of the combination of tomato peel extract and tomato seed oil according to the invention on S100A7 expression in reconstructed human epidermis In this study, the effect of a combination of tomato peel extract and tomato seed oil (as prepared in Example 2) was investigated in a reconstructed human epidermis (RHE) model by assessing S100A7 expression using in situ immunolabeling and image analysis.

[0157] Abbreviation AU Arbitrary Unit GAM Goat Anti-Mouse PBS Phosphate Buffered Saline PI Propidium Iodide PMA Phorbol Myristate Acetate RHE Reconstructed human epidermis Sd standard deviation sem Standard error of the mean

[0158] Materials and Methods Biological Model - Epidermis: Reconstructed human epidermis (RHE), 10 days old - Culture conditions: 37℃, CO25% - Assay medium: Maintenance medium

[0159] Test samples and combinations (Table 4)

[0160] [Table 5]

[0161] Culture and treatment On day 10, RHE were placed in assay medium in 12-well plates. RHE were topically treated with mineral oil (2.5 μl / RHE, ref M5904 Sigma Aldrich / Merck, CAS number 8042-47-5) as a placebo control or with the test article combination (2.5 μl / RHE). All experimental conditions were performed with n=3.

[0162] Paraffin embedding and sectioning RHE were fixed in formaldehyde solution. Fixed tissues were dehydrated in multiple baths of increasing concentration of ethanol and then embedded in paraffin. Transverse sections were made on a microtome (5 μm thick, one slide per RHE) and kept at room temperature until immunohistolabeling.

[0163] In situ immunofluorescence labeling To optimize antigen-antibody interactions, sections were deparaffinized and incubated in the target solution for retrieval at 92 °C, pH 6. These sections were cooled to room temperature in the same solution. After saturation with PBS-Tween-5% milk, sections were then incubated for 1 h with the appropriate primary antibody (anti-S100A7). After several washes, the binding sites recognized by the primary antibody were revealed with a secondary fluorescent appropriate antibody (GAM Alexa-488) and cell nuclei were stained with a propidium iodide (PI) solution. Sections were washed with PBS-Tween and mounted with fluorescent mounting medium.

[0164] Microscopic observation Sections were viewed using a NIKON microscope (40x objective) equipped with a Nikon camera. Images were processed with NIS-Elements software. Five images were captured per copy.

[0165] Fluorescence intensity was measured on images captured using ImageJ software.

[0166] Fluorescence intensity values ​​were normalized to epidermal area.

[0167] Data Management Raw data was analyzed using Microsoft Excel®.

[0168] Between-group comparisons were performed by the nonparametric Kruskal-Wallis test, followed by Dunn's multiple comparison test.

[0169] Standard error of the mean: sem = Sd / √n. The standard error of the mean (sem) is a measure of how far a sample mean is likely to be from the true population mean. The sem is calculated as the sd divided by the square root of the sample size.

[0170] result The results obtained are summarized in Table 5.

[0171] [Table 6]

[0172] Under basal conditions, the S100A7 signal was weak and localized to the granular layer of the epidermis.

[0173] Under the experimental conditions of the assay, the combination of tomato peel extract according to the invention and organic seed oil (1 / 49) and the combination of tomato peel extract according to the invention and organic seed oil and mineral oil (1 / 2 / 47), tested at 2.5 μl / RHE, induced a significant stimulation of S100A7 expression (3190% - Dunn's test p<0.001 of control, - and 1009% - Dunn's test p<0.05 of control, respectively).

[0174] conclusion The combination of tomato peel extract according to the invention and organic seed oil (1 / 49) and the combination of tomato peel extract according to the invention, organic seed oil and mineral oil (1 / 2 / 47) increased the expression of S100A7 protein, thus confirming the upregulation of the gene encoding the antimicrobial peptide (S100A7A) previously observed in example 3. We also observed better results with the combination of tomato peel extract according to the invention and organic seed oil (1 / 49) than with the combination of tomato peel extract according to the invention, organic seed oil and mineral oil (1 / 2 / 47).

[0175] Example 5 In vivo anti-irritant evaluation the goal To evaluate the soothing effect of a combination of tomato peel extract and tomato seed oil (as prepared in Example 2) after capsaicin-induced skin irritation for 120 minutes in 20 volunteers.

[0176] methodology Twenty volunteers (female) between 45 and 65 years of age with visible signs of dry and sensitive skin were included in the study. Four independent experimental areas were defined on the forearm of each volunteer included in the assay. Mild skin irritation was induced in each experimental area by exposure to a capsaicin occlusive patch for 1 hour. The occlusive patch was prepared and applied by the investigator to the four independent experimental areas of the forearm. After removing the patch, the investigator applied the test product (3-4 mg / cm2) to the corresponding experimental area. The skin erythema level was quantified using a Mexameter® at five different time points: before the start of treatment (T0), immediately after inducing mild skin irritation with the capsaicin occlusive patch (T1 after erythema induction), and 10 minutes (T2), 30 minutes (T3), 90 minutes (T4), and 120 minutes (T5) after the first application. The change in erythema level at each time point was normalized to the state at T1 after the challenge. All data were statistically analyzed. Dermatological surveillance was also included in this study.

[0177] sample: The products tested were as follows: 1 - Placebo serum formula (98% water + phenoxyethanol + sodium stearoyl glutamate + succinoglycan · chlorphenesin) 2 - Extract according to the invention at a concentration of 1% (Test 1%) in a placebo serum formulation 3 - Extract according to the invention at a concentration of 2% (Test 2%) in a placebo serum formulation

[0178] result The results are shown in Figure 1. The results showed that one hour of treatment with the capsaicin occlusive patch significantly increased the erythema levels in the four experimental areas, thus effectively inducing skin irritation.

[0179] After induction of irritation, when the products were compared to untreated controls, the results showed that "Test 2%" reduced erythema levels by 62.11% after 30 minutes, 49.55% after 90 minutes, and 56.53% after 120 minutes of treatment, while "Test 1%" reduced erythema levels by 59.52% after 30 minutes, 52.55% after 90 minutes, and 75.47% after 120 minutes of treatment.

[0180] Additionally, "Test 2%" demonstrated reduced skin irritation compared to "Placebo" as evidenced by a 58.61% reduction in erythema after 30 minutes; similarly, "Test 1%" demonstrated a 56.01% reduction in erythema compared to "Placebo".

[0181] It is noteworthy that no significant differences in erythema levels were observed between "placebo" and no treatment at any of the time points tested.

[0182] Regarding skin compatibility and acceptability, none of the volunteers showed any skin acceptability problems and no skin reactions during the treatment.

[0183] In conclusion, this clinical trial shows that the products "Test 1%" and "Test 2%" have an efficient soothing effect on skin irritation and therefore reduce skin irritation.

[0184] Example 6 In vivo moisturizing and barrier function evaluation the goal In vivo evaluation of moisturizing and barrier function of the three treatments (test product at 0.5% and 1%, and placebo) after topical application to the forearm. The kinetics of the measurements were established as follows: T0 (before treatment), 30 minutes, 90 minutes, 120 minutes and 24 hours after application.

[0185] Application area: forearm. Platform: Thirty volunteers (women between 40 and 70 years old with dry and sensitive skin). The inclusion criteria for the selection of volunteers with sensitive skin conditions are as follows: - Female, 40-70 years old. - Skin phototypes (Fitzpatrick): II, III and IV. - Subject is in good general health (not merely the absence of disease / ill-health but physical, mental and social well-being) according to self-report. - Subjects with visible signs of dry and sensitive skin (subjects diagnosed with sensitive skin with positive questionnaire and lactic acid test). The questionnaire is positive if the subject reflects a recent and recurrent history of functional symptomatology of skin discomfort, and the lactic acid test in the nasolabial fold is positive if itching is detected in the nasolabial fold 3 minutes after application of 1 mL of 10% aqueous lactic acid). - Subjects with visible signs of dry and sensitive skin.

[0186] On the other hand, the exclusion criteria are as follows: - Allergy or reactivity to some of the ingredients of this product or to products of a similar category to the test product. - Associated skin marks (scars, sunburn, etc.) in the experimental area that may interfere with the measurements. - Relevant pharmacological or hormonal treatments in use. - Presence of skin disease or melanoma.

[0187] sample The products tested were as follows: 1) Placebo serum composition (= 98% water + phenoxyethanol + sodium stearoyl glutamate + succinoglycan · chlorphenesin) (P.2328) 2) Extract according to the invention at a concentration of 1% (P2330 1%) in a placebo serum formulation 3) Extract according to the invention at a concentration of 0.5% (P2329 0.5%) in a placebo serum formulation

[0188] Methodology: Mild skin irritation was induced in each of four independent experimental areas on the forearm by researchers rubbing them with natural pumice 20 times.Before starting treatment, the inventors confirmed damage to the skin barrier by measuring whether TEWL increased two-fold using Tewameter®.After this effect was achieved, the researchers applied the test product to the corresponding experimental area.

[0189] Skin hydration was quantified using a Corneometer® at five different time points: after inducing mild skin irritation with natural pumice (T0 after skin irritation), and 30 min (T1), 90 min (T2), 120 min (T3) and 24 h (T4) after the first application. After checking for normal distribution of the data, a two-way paired ANOVA statistical test was applied to statistically analyze the results.

[0190] result The results regarding the hydrating effect of the cosmetics are shown in Figures 2A and 2B (Figure 2A for P2330 1% and Figure 2B for P2329 0.5%). The inventors can observe a significant increase in skin hydration after applying the extract according to the invention in concentrations of 0.5% and 1% to a placebo serum formulation. Such an increase is not observed after applying the placebo formulation.

[0191] Quantification and measurement of TEWL levels was also performed using a Tewameter®. Preliminary results showed a significant decrease in TEWL levels 90 minutes after application of P2330 1% and P2329 0.5%.

[0192] Example 7 Cosmetics and Nutritional Supplements Example 7a Skin immune stimulating cream for sensitive skin A skin immune stimulating cream (for sensitive skin) can be prepared by combining the ingredients set forth in Table 6 below, the cream containing the peel extract of Solanum lycopersicon fruit (tomato) of the present invention, named Solanum lycopersicon (tomato) peel wax.

[0193] [Table 7]

[0194] Example 7b Highly functional cleansing balm A high performance cleansing balm can be prepared by combining the ingredients set forth in Table 7 below, the balm containing the peel extract of Solanum lycopersicon fruit (tomato) of the present invention, named Solanum lycopersicon (tomato) peel wax.

[0195] [Table 8]

[0196] Example 7c Cream for preventing or treating atopic skin disorders A cream for preventing or treating atopic skin disorders can be prepared by combining the ingredients as set forth in Table 8 below, wherein the cream contains the peel extract of Solanum lycopersicon fruit (tomato) of the present invention, named Solanum lycopersicon (tomato) peel wax.

[0197] [Table 9]

[0198] Example 7d Facial cleansing foam A cleansing agent (facial cleansing foam) for atopic skin containing the peel extract of Solanum lycopersicon fruit (tomato) of the present invention, named Solanum lycopersicon (tomato) peel wax, is formulated by combining the ingredients listed in Table 9 below.

[0199] [Table 10]

[0200] Example 7e Immune Boost After-Sun Serum for Sensitive Skin An immune boost serum (for oily skin) containing the peel extract of Solanum lycopersicon fruit (tomato) of the present invention, named Solanum lycopersicon (tomato) peel wax of the present invention, is formulated by combining the ingredients listed in Table 10 below.

[0201] [Table 11]

[0202] Example 7f Tomato Immune Lipstick Formulation: A tomato immunity lipstick formulation containing the peel extract of Solanum lycopersicon fruit (tomato) of the present invention, named Solanum lycopersicon (tomato) peel wax, is formulated by combining the ingredients listed in Table 11 below.

[0203] [Table 12]

[0204] Example 7g Oral capsules for food supplements or nutricosmetic supplements to boost immunity: An orally ingestible capsule containing the peel extract of Solanum lycopersicon fruit (tomato) of the present invention, named Solanum lycopersicon (tomato) peel wax, is formulated by combining the ingredients as set forth in Table 12 below.

[0205] [Table 13]

[0206] Example 7h Dandruff prevention or treatment shampoo (for sensitive scalp) An anti-dandruff or treatment shampoo formulation containing the peel extract of Solanum lycopersicon fruit (tomato) of the present invention, named Solanum lycopersicon (tomato) peel wax, is formulated by combining the ingredients set forth in Table 13 below.

[0207] [Table 14]

Claims

1. For maintaining, balancing or enhancing the natural defenses of the skin or mucous membranes, containing, based on the total mass of the extract, at most 0.5% by mass of lycopene, at least 5% by mass of amylins and at least 1.5% by mass of sterols, the cosmetic use of a peel extract of lipophilic Solanum lycopersicum fruits.

2. The cosmetic use according to claim 1, wherein the peel extract of lipophilic Solanum lycopersicum fruits is used for enhancing the skin barrier function and / or for maintaining or increasing the skin's resistance or tolerance to external attacks or stress and / or for preventing or treating non-pathological changes in the skin caused by external attacks or stress.

3. The cosmetic use according to claim 1 or 2, wherein the peel extract of lipophilic Solanum lycopersicum fruits is used as an anesthetic.

4. The cosmetic use according to claim 1 or 2, wherein the peel extract of lipophilic Solanum lycopersicum fruits is used for improving or restoring the skin comfort and / or for restoring and / or maintaining a healthy skin microbiome.

5. The cosmetic use according to claim 1 or 2, wherein the peel extract of lipophilic Solanum lycopersicum fruits induces the expression of antimicrobial peptides (AMP).

6. The cosmetic use according to claim 1 or 2, wherein the peel extract of lipophilic Solanum lycopersicum fruits is used in combination with a vegetable oil or a mineral oil.

7. The cosmetic use according to claim 6, wherein the peel extract of lipophilic Solanum lycopersicum fruits is used in combination with Solanum lycopersicum seed oil.

8. The cosmetic use according to claim 6, wherein the mass ratio of the peel extract of lipophilic Solanum lycopersicum fruits to the vegetable oil or mineral oil is from 1:2 to 1:

70.

9. The cosmetic use according to claim 6, wherein the vegetable oil and the peel extract of lipophilic Solanum lycopersicum fruits are obtained by co-extraction or separate extraction of tomato by-products.

10. The cosmetic use according to claim 1 or 2, wherein the peel extract of lipophilic Solanum lycopersicum fruits contains at most 0.3% by mass of lycopene, based on the total mass of the extract.

11. The cosmetic use according to claim 1 or 2, wherein the amylins are α - amylase, β - amylase and / or δ - amylase.

12. The cosmetic use according to claim 11, wherein the peel extract of lipophilic Solanum lycopersicum fruits contains at least 1.5% by mass of α - amylase, at least 1% by mass of β - amylase and at least 2.5% by mass of δ - amylase based on the total mass of the extract.

13. The cosmetic use according to claim 1 or 2, wherein the peel extract of lipophilic Solanum lycopersicum fruits contains at least 1% by mass of β - sitosterol and stigmasterol based on the total mass of the extract.

14. The cosmetic use according to claim 1 or 2, wherein the peel extract of lipophilic Solanum lycopersicum fruits is present in a cosmetic composition for topical administration at a mass content of 0.01% - 30% based on the total mass of the composition, and the composition contains at least one excipient acceptable as a cosmetic.

15. The cosmetic use according to claim 1 or 2, wherein the peel extract of lipophilic Solanum lycopersicum fruits, a combination of the peel extract of lipophilic Solanum lycopersicum fruits and vegetable oil, or a cosmetic composition is topically applied or orally administered to a healthy subject having sensitive skin, dry skin, aging skin, blemish - prone skin, acne - prone skin, atopic - prone skin, or skin weakened by external invasion or stress.

16. An oral or topical composition for use as an active ingredient in the treatment and / or prevention of blemish - prone skin, acne - prone skin, and / or atopic - prone skin, containing a peel extract of lipophilic Solanum lycopersicum fruits containing up to 0.3% by mass of lycopene, at least 5% by mass of amylins, and at least 1.5% by mass of sterols based on the total mass of the extract.

17. An oral or topical composition for use as an active ingredient in the treatment of skin diseases characterized by changes or imbalances in the innate immune response, containing a peel extract of lipophilic Solanum lycopersicum fruits containing up to 0.5% by mass of lycopene, at least 5% by mass of amylins, and at least 1.5% by mass of sterols based on the total mass of the extract.

18. - Up to 0.3% by mass of lycopene based on the total mass of the extract; - At least 5% by mass of amyrins, in particular α - amyrin, β - amyrin and / or δ - amyrin, based on the total mass of the extract; - At least 1.5% by mass of sterols based on the total mass of the extract A peel extract of lipophilic Solanum lycopersicum fruits containing the above.

19. A cosmetic composition comprising the peel extract of lipophilic Solanum lycopersicum fruits according to Claim 18 and at least one excipient acceptable as a cosmetic.

20. The cosmetic composition according to Claim 19, wherein the peel extract of lipophilic Solanum lycopersicum fruits has a mass content of 0.01% to 30% based on the total mass of the composition.

21. A beauty care method for the skin and / or mucous membranes from the viewpoint of improving the condition and / or appearance of the skin and / or mucous membranes, comprising the step of topically applying or orally administering a peel extract of lipophilic Solanum lycopersicum fruits, wherein the extract contains at most 0.5% by mass of lycopene, at least 5% by mass of amyrins and at least 1.5% by mass of sterols based on the total mass of the extract.

22. For maintaining, balancing or strengthening the natural defense of the skin or mucous membranes; in particular, for strengthening the barrier function of the skin and / or for maintaining or increasing the resistance or tolerance of the skin to external attacks or stress and / or for preventing or treating non - pathological changes of the skin caused by external attacks or stress; and / or for improving or restoring the comfort of the skin and / or for restoring or maintaining a healthy skin microbiome. The beauty care method according to Claim 21.

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