Powdered extracts of delipidated plant parts and their cosmetic uses.

Abstract

Cosmetic use of semolina-type powders made from delipidated extracts of plant parts with multifunctional effects that can be usefully combined and prepared extemporaneously just before the formulation of the final cosmetic product and intended to be brought into contact with the various superficial parts of the human body.

Description

Title of the invention: Powdered extracts of delipidated plant parts and their cosmetic uses.

[0001] A cosmetic product is defined as any substance or mixture intended to be placed in contact with the superficial parts of the human body (the epidermis, the hair and scalp systems, the nails, the lips and the external genital organs) or with the teeth and the oral mucosa, with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance, protecting them, keeping them in good condition or correcting body odors.

[0002] This definition is important for several reasons, including contact with the superficial parts of the human body without limitation of penetration, but especially with a view to exclusively or primarily achieving certain effects, which do not exclude effects on genes, both in stimulation and inhibition. Indeed, a simple caress on the skin affects a whole cascade of genes, and it would be unrealistic to claim that simply because a gene is either stimulated or inhibited, this is irrelevant to cosmetics. The popular science magazine Vogue, concerned with beauty and cosmetics, is well aware of this, and one of their articles from October 2016 explains it: Anti-aging shielding: internal protection, right down to our genes (www.vogue.fr / beaute / en-vue / diaporama / protection-interne-anti-age-soin-peau / 38207).

[0003] In conventional cosmetics, these objectives for these products imply the use of active substances in addition to the ingredients used to achieve its texture.

[0004] Due to the growing interest in organic ingredients instead of synthetic ones, users of cosmetic products are increasingly demanding natural ingredients such as plant extracts.

[0005] It is also worth noting that it is often forgotten that the skin is an important organ in relation to all the others. Consequently, everything we apply to our skin is more or less absorbed and comes into contact with our entire body, hence the importance of avoiding synthetic ingredients and preferring natural substances, including plant extracts.

[0006] This corresponds to the trend of organic-labeled cosmetics or those claiming to be simply natural, such as the "green beauty" trend, largely derived from organic farming or the harvesting of wild plants, all linked to respect for the environment and our health. These organic or natural formulations are composed primarily of plant extracts.

[0007] Negative lists of controversial substances found in conventional brands are emerging and bringing about a real challenge to the industry conventional cosmetics. This trend benefits from a fundamental movement that extends far beyond the world of beauty, hygiene and care.

[0008] It is part of a more fundamental trend of seeking well-being, independence, and more responsible consumption with the feeling of acting in favor of the planet. Thus, a hunt is on for microplastic particles, parabens, aluminum salts, glycol ethers, BHT and BHA, titanium dioxide, nanoparticles, silicones, triclosan and especially endocrine disruptors.

[0009] Until 2010, there was no common European legislation, which is why several organic labels were created, each with specifications adapted to its specific legislation. These specifications are constantly evolving and depend on general regulations and technological developments. To be certified by an organic label, a product must meet all the conditions imposed by the label's established specifications and pass inspections by independent and recognized bodies.

[0010] A distinction must also be made between products of organic origin and products of natural origin. Ingredients of organic origin are plants, honey, milk, etc., obtained organically. Only these ingredients are taken into account when calculating the percentage of organic products in a cosmetic product, excluding water.

[0011] Therefore, we observe that more and more cosmetics are trying to claim a more organic, more ecological, more natural mode of action with the new ISO 16128 standard, vegan, and even a slow cosmetics approach (ecological, healthy, intelligent, and reasonable) that takes into account the skin's real needs, advocating the use of fewer ingredients to achieve better results, even frugality, positive contributions for the skin, and realistic promises. One response to this concern could then be plant extracts with multiple, multifunctional, and complementary properties that are sufficient on their own and often do not require the addition of other active substances in cosmetic formulations.

[0012] It is also known that from a Corporate Social Responsibility (CSR) and sustainable development point of view, raw materials which come from far away with high weight and volume are becoming less and less attractive to cosmetics companies and their customers.

[0013] To qualify for the organic label, a cosmetic product must meet a number of conditions, primarily a minimum percentage of organic substances. Some labels, such as NATRUE and BDIN, exclude water from the formula as an organic ingredient, even though it often contains around 50%, thus reducing the chances of obtaining these labels. Furthermore, most organic standards do not consider water in formulas, which often exceeds 50% by mass or volume, in their calculations.

[0014] It is also known that extracts solubilized in water pose preservation problems, the resolution of which often conflicts with the preservation system of the final cosmetic product and affects its quality.

[0015] It is also evident that the ingredients offered by suppliers to the cosmetics industry are subject to fixed order quantities. In the case of water-extracted substances in particular, this involves minimum quantities and fixed container sizes. For example, 5 liters, 10 liters, 100 liters, etc. The problem is that in manufacturing, such volumes are rarely used, which poses problems for both the storage and preservation of leftovers.

[0016] On the other hand, and in order to claim a maximum number of different effects, recent years have seen an increase in the number of these active ingredients in a single formula. These ingredients are necessarily present individually in small quantities, thus resulting in formulations with low concentrations of high-quality active ingredients, and therefore, paradoxically, ineffective. For example, patent application FR3145487 describes, among other things, a cosmetic process combining six plant extracts with a chamomile extract and an arnica extract.

[0017] Or, for example, the document "Hair Essence", XP055795232 disclosing a leave-in hair product with the use of at least 11 plant extracts, all located at the end of the full labelling, in order to condition the scalp and its environment and make the hair healthy.

[0018] This problem of overabundance of active ingredients in the same formulation has recently given rise, in reaction, to skinimalism, the less is more trend, which was born from the idea of ​​returning to the essentials and simplifying our skin care routine while preserving the planet.

[0019] Indeed, at a time when environmental issues have become central and essential, skinimalism also appears as ideal for adopting a greener and more sustainable beauty routine, with natural products and therefore essentially plant extracts.

[0020] Plant extracts offered to the cosmetics industry are often produced using toxic solvents such as, but not limited to, hexane, petroleum ethers, 3-chloro-2-hydroxypropyl, butanol and propanol, concentrated sulfuric acid, methanol, acetone, methyl ethers, and heptane. This contradicts the desire for naturalness, even if these solvents are often evaporated or separated from the extract as much as possible afterward. In any case, this production method is not very environmentally friendly. These solvents are often used to extract lipid fractions or to delipidate these extracts for further processing, as well as for analytical purposes (AOAC).

[0021] In other cases the solvent is natural, such as water, ethanol, or glycerol. In this case, however, the oils, waxes, and other lipids contained in the plant hinder the extraction of compounds of interest, and removing them beforehand would be of great benefit.

[0022] In all cases these extracts are characterized by a large final volume corresponding to the active part and the solvent, which is not very environmentally friendly if we consider their packaging for large volumes, their storage and their transport.

[0023] These extracts also require a preservation system that is not harmless and is qualitatively and quantitatively superimposed on that of the final cosmetic formula, which is a problem for the formulator and the final formula and especially for the end user.

[0024] Among all the patent applications concerning studied plants, Adansonia digitata of the Malvaceae family discloses numerous known properties when used as a whole and particularly its oil. Indeed, the oil of this plant is traditionally used in West Africa to restore softness and elasticity to the skin, relieve and soothe superficial burns, prevent stretch marks, and is often applied to brittle, dry, dull, or split nails or hair to restore their shine and beauty. This oil is produced from seeds surrounded by a dry pulp when ripe and contained in a fruit often called monkey bread.

[0025] A patent application FR2310112 discloses the interest of water-soluble extracts of delipidated seeds of this plant in a cosmetically acceptable vehicle such as water, hydroalcoholic solutions, glycerol, which avoids the problems listed above and which the present application solves.

[0026] The invention further discloses the cosmetic use of water-soluble extract of delipidated seeds of Adansonia digitata of the Malvaceae family intended to be used to induce stimulation of the expression of genes involved in the keratinocyte differentiation process (KLK7, KLK10, KRT1, SPRR1A, 2A, ;2D, 2E, CDSN, FLG, IVL, KLK8, CRABP2, SCEL) knowing that: SPRR IA, 2A, 2D, 2E correspond to small proteins released during the maturation or differentiation of keratinocytes and which are then taken up by transglutaminases at the level of the stratum corneum to form the corneal envelope surrounding the keratinocytes giving them sufficient rigidity to allow good cohesion and therefore an essential barrier effect as well as a beautiful appearance on the surface of the skin, KRT1, KLK7, KLK8 and KLK10 for Keratin 1, 7, 8 and 10 are keratins and intermediate filaments of the cytoskeleton playing an important role in maintaining the functional skin barrier, ; IVL is the gene that produces Involucrin, which serves as a primer for the binding of other molecules in the corneal envelope. FLG for Filaggrin is synthesized in the form of profilaggrin which is then broken down into filaggrin subunits which associate at the end of the epidermal maturation process with the intra-corneocyte fibrous intermediate filaments thus participating in the comification of corneocytes. CDSN, or Comeodesmosin, is a protein specific to corneodesmosomes responsible for the adhesion of corneocytes to each other, thereby contributing to the barrier effect on the skin surface and to epidermal firmness. CRABP2, or Cellular Retinoic Acid Binding Protein 2, participates in epidermal maturation. SCEL gene encoding Sciellin, a precursor protein of the corneal envelope and keratinocyte differentiation. The epidermis therefore sees its keratinocytes differentiate better, its horny envelopes form better, as a result of which the skin will be more beautiful on the surface, more resistant to the harmful effects of aging and presenting a better quality barrier effect.

[0027] This allows obtaining a water-soluble extract of delipidated seeds of Adansonia digitata of the Malvaceae family characterized in that it is intended to be applied to healthy skin to strengthen and promote on the one hand the good maturation and differentiation of the skin allowing it to be more beautiful on the surface, more resistant to the harmful effects of external aggressions and aging because it presents a better quality barrier effect and on the other hand by slowing down cell proliferation thus giving more time to the epidermis to build itself up better and improve its firmness. More precisely, a water-soluble extract of defatted seeds of Adansonia digitata, from the Malvaceae family, is disclosed for the treatment or prevention of negative effects caused by the slowing of proper keratinocyte maturation and differentiation, all linked to an underexpression of Small Proline Rich Proteins 2A and 2D (SPRR2A and 2D), Lipocalin 2 (LCN2), Suprabasin (SBSN) and Corneodesmosin (CDSN), Dermokine (DMKM) and Filaggrin (FLG), or, conversely, in the context of the overexpression of genes promoting skin problems, cell hyperproliferation, and extracellular matrix degradation, such as Matrix Metallopeptidases 1 and 3 (MMP 1 and 3), Tenascin C (TNC), Interleukin 33 (IL33), and Stathmin-like3 (STMN3). Indeed, Small Proline Rich Proteins are small proteins rich in proline and are naturally encoded by the SPRR2A and 2D genes. In the skin, they are precursors of the horny envelopes and participate in the development of the epidermis and its comification. Lipocalin-2 is a protein encoded by the LCN2 gene and participates in skin homeostasis as well as limiting bacterial growth and therefore plays a role in the skin barrier effect. Suprabasin is also a protein encoded by the SBSN gene, playing an important role in the skin barrier, and its reduction is responsible for atopic dermatitis. Comeodesmosin (CDSN) is a specific protein of corneodesmosomes responsible for the adhesion of corneocytes to each other and thus participates in the barrier effect on the surface of the skin and in epidermal firmness. Dermokine is a glycoprotein encoded by the DMKM gene, the under-expression of which results in a breakdown of the epidermal barrier effect, the appearance of scales and wrinkles, and the fragility of the stratum corneum. Filaggrin (FLG) is synthesized in the form of profilaggrin which is then broken down into filaggrin subunits which associate at the end of the epidermal maturation process with the intra-corneocyte fibrous intermediate filaments thus participating in the comification of corneocytes. Matrix metalloproteinases are peptidases encoded by MMP genes and are responsible for the more or less controlled degradation of the extracellular matrix. In certain situations, limiting their production proves beneficial. Tenascin C is a protein encoded by the TNC gene and plays a role in cell proliferation. Its activity is increased by MMPs. Reducing the expression of these two types of proteins, TNC and MMP, is highly complementary when the goal is to protect the extracellular matrix and reduce cell proliferation, thus giving the skin more time to regenerate. Interleukin 33 (IL33) is a cytokine that, when expressed excessively following inflammation, also stimulates cell proliferation. Reducing its expression thus helps control cell division. Stathmin-3 is a protein encoded by the STMN3 gene that destabilizes the cytoskeleton, particularly tubulin, when overexpressed. Reducing its expression in healthy skin is undoubtedly beneficial. It must then be noted that all of these genes act directly and indirectly on the barrier effect of the skin and clearly illustrates the maxim: The epidermis, a barrier on all fronts! Other effects related to the reduction of cell proliferation also contribute to this effect because they allow the skin more time to build itself up properly, more time to better establish this barrier effect that allows the skin to be more beautiful and firmer on the surface, more resistant to the harmful effects of external aggressions and aging.

[0028] Among all the plant extracts disclosed is Cyperus esculentus, from the Cyperaceae family, which is used primarily for its oil obtained by pressing the tubers of this rhizomatous plant. It is an edible plant whose tubers are harvested to obtain, among other things, a valuable oil. The Arabs and Egyptians already used it for cosmetic purposes due to its nourishing, revitalizing, and antioxidant effects, and also in food to impart a flavor reminiscent of almonds. It is also used for a variety of internal and external treatments, such as the prevention of cardiovascular disorders, the reduction of post-meal glucose levels, the increase in mitochondrial formation, and the prevention of cognitive impairment.

[0029] Patent applications FR2310113 and FR10099 disclose the interest of water-soluble extracts of delipidated tubers of this plant in a cosmetically acceptable vehicle such as water, hydroalcoholic solutions, glycerol, which raises the problems listed above and which the present application resolves.

[0030] Compositions are disclosed therein for their use in the treatment or prevention of the negative effects caused by the growth or regrowth of unsightly hair or hair, all linked to an over-expression of Wingless-type 4 and Wingless type 10A proteins (WNT 4 and WNT10A) or, on the contrary, by an increase in localized adipose tissue in the context of an under-expression of Angiopoietin like 4 (ANGPTL 4).

[0031] Among all the other plant extracts disclosed are 2 species of Loofah (Luffa acutangula, Luffa cylindrica and Luffa aegyptiaca) Loofah or Loufa in French; Diampe Nier in Senegal; Peerkankai or Beera kaya in India.

[0032] These plants are cultivated and their fruits are picked before maturity to be consumed as a vegetable in Asia and Africa.

[0033] Loofah seed is used in cosmetics to produce an oil with repairing and nourishing properties which provides lipids to the epidermis without leaving a greasy film on the surface.

[0034] The water-soluble extract of these Loofah seeds has significant cutaneous effects on hydration, improvement of tone and firmness, tightening and anti-wrinkle effects or improvement of skin tone radiance, while having the rare property of not acting significantly or acting very little on the expression of the human genome and never on any cell signaling pathway which avoids the risk of genetic and metabolic disruption.

[0035] French patent FR31144507 discloses the interest of water-soluble extracts of delipidated seeds of this plant in a cosmetically acceptable vehicle such as water, hydroalcoholic solutions, glycerol, which poses the problems listed above and which this application resolves.

[0036] Also among all the disclosed plant extracts is Xylopia aethiopica, an African plant of the Annonaceae family. It has numerous and well-known properties and is a species commonly used in tropical Africa as a spice and for the medicinal properties of its fruits and seeds. Analysis of the fatty acids in the seeds confirms the absence of toxic compounds, thus justifying the common use of the fruits in food. The curative properties of the fruit of Xylopia aethiopica are justified by its antimicrobial and antifungal activity. Its dried fruit is used as a spice and for its medicinal properties, particularly against influenza, bronchitis, and dysentery. It is also recommended for relieving eye-related conditions. In Senegal, it is used to flavor Touba coffee, a drink that has become traditional.

[0037] A patent application FR2310111 discloses the interest of water-soluble extracts of delipidated fruits and seeds of this plant in a cosmetically acceptable vehicle such as water, hydroalcoholic solutions, glycerol, which raises the problems listed above and which the present application resolves.

[0038] And more specifically a water-soluble extract of delipidated fruits or seeds of African Xylopia aethiopica of the Annonaceae family for the treatment or prevention of the negative effects caused by aging, an alteration of the skin's barrier effect, its cohesion and homeostasis, an increase in epidermal proliferation not allowing it to build up completely and correctly, without sufficient maturation and differentiation with fragile horny envelopes;when the negative effects also concern extracellular matrices that are too degraded by peptidases and with poor collagen formation leading to a loss of firmness, all linked to an under-expression of Insulin-like Growth Factor Binding Protein 3 (IGFBP3), TransGlutaMinase 1 (TGM1), Capsasel4 (Capsl4), Desmoglein 1 (DSG1), DeCoriN (DCN) or, conversely, in the context of the over-expression of genes promoting skin problems, the destruction of extracellular matrices and the loss of homeostasis, such as Matrix MetalloPeptidases 1, 3 and 10 (MMPI,3,10), XIAP Associated Factor 1 (XAF1) and TransGlutaMinase 2 (TGM2).

[0039] Indeed, Insulin-like Growth Factor Binding Protein 3 (IGFBP3) is a true marker of aging, which decreases when senescence is induced in skin cell culture by hydrogen peroxide (H2O2) compared to cells that remain young. There is therefore a cosmetic benefit to increasing its expression physiologically. Increased ITGFBP3 expression induces a partial inhibition of the processes of proliferation, division, and progression of the epidermal cell cycle. This allows the epidermis and its stratum corneum more time to properly develop, a process further enhanced by Capsase 14 when its expression is also higher. Capsacel4 is a protease encoded by the CAPS 14 gene and plays a central role in apoptosis, acting as a true regulator of cellular homeostasis, as well as in the terminal differentiation of keratinocytes. It thus provides a barrier effect for the skin and regulates transepidermal water loss, which has ample time to be expressed when FIGFBP3 is active. Apoptosis is inhibited by two genes, XIAP Associated Factor 1 (XAF1) and Transglutaminase 2 (TGM2), which are specifically inhibited by the water-soluble extract of delipidated fruits or seeds of Xylopia aethiopica. Therefore, reducing their expression is beneficial for skin homeostasis. Desmoglein, on the other hand, is a desmosomal protein naturally encoded by the DSG1 gene, predominantly expressed in the last layers of the epidermis and responsible for the adhesion properties of the famous desmosomes, a veritable snap fastener, ensuring the cell-cell junction essential to the skin's barrier effect and cohesion. Transglutaminase 1 (TGM1) is an enzyme that enables the polymerization of proteins that will form the corneal envelope during the terminal differentiation of keratinocytes into comeocytes. Decorin is a protein encoded by the DCN gene that binds around collagen fibers to control their diameter, which is thus homogeneous in the extracellular matrix, guaranteeing firmness, homogeneity which degrades like firmness during aging. Matrix metallopeptidase 1 (MMPI) is an enzyme encoded by the MMPlet gene, which belongs to a group of MMP genes that degrade the extracellular matrix by attacking its fibers, such as collagen, as well as growth factors, often hindering wound healing. MMP3 and MMP10 are stomelysins that degrade several types of collagen, as well as fibronectin, laminin, and elastin, all of which play a role in skin firmness. These 3 MMPs, significantly inhibited by the said extract, all participate in the dismantling of the extracellular matrix and reducing their expression is therefore favorable to maintaining skin firmness.

[0040] Similarly, among all the disclosed plant extracts, Hibiscus sabdariffa and its various varieties from the Malvaceae family have numerous and well-known properties when used as a whole, and particularly its oil. Indeed, the oil of this plant is traditionally used in West Africa to restore softness and elasticity to the skin, and to relieve and soothe burns. superficial and is often applied to brittle, dry, dull or split ends to restore shine and beauty.

[0041] A patent application FR2310101 discloses the interest of water-soluble extracts of delipidated seeds of this plant in a cosmetically acceptable vehicle such as water, hydroalcoholic solutions, glycerol, which raises the problems listed above and which the present application resolves.

[0042] One method thus disclosed would make it possible to reduce localized weight gain, also called cellulite, using a single multifunctional extract is to activate the expression of the genes of Angiopoietin (ANGPTL4), Perilipin 2 (PLIN2), GO / G1 Switch (GOS2), Camitin palmitoyl transferase (CPT1A); Indeed, ANGPTL4 inhibits lipoprotein lipase and pancreatic lipase, the latter promoting the storage of fatty acids in adipocytes, which is the cause of the so-called cellulite. PLIN2, perilipin or adipophilin ensures the maintenance of adipose tissue. GOS2 adds a circadian effect to fat storage and is highly present in subcutaneous adipose tissue. And CPT1A promotes lipid degradation in mitochondria.

[0043] The invention also discloses a method of stimulating the skin's natural antimicrobial defenses, its microbiota and microbiome, using a single multifunctional extract, which is to activate the expression of antimicrobial peptides and their genes (S100A7, 8, 9) and that of Defensin B1 (DEFB1). Indeed, the S100 proteins (S100A7, S100A8 and S100A9) as well as DEFB1 are antimicrobial proteins and peptides, both bacterial and fungal, ensuring the innate immune defense of the skin and effectively regulating the cutaneous microbiota and microbiome.

[0044] According to the invention, a method of promoting, with the aid of a single multifunctional extract, the proper maturation and differentiation of the skin, enabling it to be more beautiful on the surface, more resistant to the harmful effects of external aggressions and aging because it presents a better quality barrier effect, is to stimulate the expression of the genes of Claudin 4 (CLDN4), Occludin (OCLN), Small Proline Rich Proteins 2A (SPRR2A), Sciellin (SCEL), Epiregulin (EREG), Serpine B1 and B2 (SERPIN B1 and B2) and to reduce the expression of the genes of Matrix Metalloproteinases 1 and 10 (MMP3, MMP10) and Chemokine 14 (CXCL14). Indeed, CLDNA codes for Claudin4, an essential component of tight junctions in the deep epidermis, which plays an important role in the skin's barrier effect and the control of its insensible water loss. Similarly, OCLN codes for Occludin, which is also located in these tight junctions, ensuring their formation, maintenance, and functions. PPRR2, EREG, Serpines G1 and G2 and SCEL, participate in the terminal differentiation of the epidermis and allow the stratum corneum and the corneal envelopes to finalize their overall barrier effect and protection against aggressions of all types. The reduction of the expression of matrix metaloproteinases such as MMP3 and MMP10, which in some situations destroy the extracellular matrix, and of CXCL14, a pro-inflammatory chemokine, contributes to maintaining this functional barrier effect in association with the antiproteinase effect of Serpins B1 and B2, which are activated elsewhere as described above.

[0045] One method disclosed according to the invention of activating the overall skin response to oxidative stress and enabling it to have a better response to xenobiotics, using a single multifunctional extract, is to activate the so-called Nrf2 signaling pathway which, when activated, plays a cytoprotective role against oxidative stress and from certain exposures to xenobiotics. This cytoprotective signaling pathway is particularly activated by stimulation of the expression of cytochrome P450 (CYP1B1), Aldo-ketoreductase 1 AKR1C1, superoxide dismutase 2 (SOD2) and Insulin-like growth factor binding protein 3 (IGFBP3) genes, which together play a cytoprotective role.

[0046] According to the invention, which discloses the water-soluble extract of delipidated seeds and / or calyces of Hibiscus sabdariffa from the Malvaceae family in order to strongly reduce the expression of the WNT4 gene which inhibits hair regrowth and make it an extract favorable to regrowth at the beginning of baldness.

[0047] Among all the plant extracts studied, Simmondsia chinensis, from the Simmondsiaceae family, has numerous and well-known properties when used as a whole, and particularly its oil, or more precisely, its wax. Indeed, jojoba oil is rich in beneficial properties and is used for a wide variety of external treatments for the skin and hair. It is also used for engine lubrication and as a fuel for lighting lamps.

[0048] A patent application FR2310102 discloses the interest of water-soluble extracts of delipidated beans and seeds of this plant in a cosmetically acceptable vehicle such as water, hydroalcoholic solutions, glycerol, which poses the problems listed above and which the present application solves.

[0049] Or more precisely, a water-soluble extract of defatted beans or seeds of Simmondsia chinensis from the Simmondsiaceae family for the treatment or prevention of negative effects caused by xenobiotics, molecules foreign to the body often requiring detoxification, oxidative and cellular stress, oxygen free radicals, and the slowing of its proper maturation and keratinocyte differentiation, all linked to an under-expression of cytochromes P450 (CYP1B1), Small Proline Rich Proteins 2A and 2D (SPRR2A and 2D), Desmoglein 1 (DSG1) and Thioredoxine reductase (TXNRD1) or, conversely, in the context of the overexpression of genes promoting skin problems, localized fibrosis or cell hyperproliferation following UV irradiation or its inflammation, such as Connective tissue growth factor (CTGF) or Jun transcription factor (c-Jun)

[0050] Indeed, cytochrome 450s and those naturally produced by the CYP1B1 gene have oxidoreductase activities complemented by the ability to metabolize toxins and reactive oxygen species, as well as xenobiotic molecules. They regulate cell proliferation and apoptosis in response to oxidative stress and influence the organization of collagen fibrils. They are found in both the skin and the hair bulb. They play an anti-pollution role and metabolize xenobiotics such as caffeine, toxins from cigarette smoke, and barbecue fumes. Small proline-rich proteins are small proteins rich in proline and are naturally encoded by the SPRR2A and 2D genes.In the skin, they are precursors of the stratum corneum and participate in the development and cornification of the epidermis via transglutaminases such as TGM1, which is also stimulated by this hydrophilic and water-soluble extract of jojoba beans or seeds. Desmoglein, for its part, is a desmosomal protein naturally encoded by the DSG1 gene, predominantly expressed in the outermost layers of the epidermis and responsible for the adhesive properties of the well-known desmosomes, veritable snap fasteners, ensuring the cell-cell junction essential to the skin's barrier function and cohesion. Thiredoxin is a reductase encoded by the TXNRD1 gene and also has oxidoreductase activity, oxidative detoxification and response to oxidative stress accelerating aging. Connective tissue growth factor (CTGF), encoded by the CTGF gene, is a matrix cell protein associated with fibrosis and human aging. Numerous studies are attempting to identify inhibitors of its activity. (Arthritis Rheum. 62 (5): 1523-32. doi:10.1002 / art.27382. PMC 3866029. PMID 20213804) The transcription factor Jun (c-Jun) is a proto-oncogene whose expression is stimulated by UV irradiation; many teams are currently searching for inhibitors of this factor, The EMBO Journal. 18 (1): 188-97. doi:10.1093 / emboj / 18.1.188. PMC 1171114. PMID 9878062.

[0051] The invention further discloses the cosmetic use of water-soluble extract of defatted beans or seeds of Simmondsia chinensis of the Simmondsiaceae family intended for use in the treatment or prevention of the effects negative effects caused by xenobiotics, molecules foreign to the body often requiring detoxification, oxidative and cellular stress, oxygen free radicals and the slowing of its proper maturation and keratinocyte differentiation characterized in that aqueous, hydroethanolic or hydroglycerin extracts are able to improve the expression of cytochromes P450 (CYP1B1), Small Proline Rich Proteins 2A and 2D (SPRR2A and 2D), Desmoglein 1 (DSG1) and Thioredoxine reductase (TXNRD1) and reduce those of Connective tissue growth factor (CTGF) or Jun transcription factor (c-Jun).

[0052] The invention further discloses the cosmetic use of a water-soluble extract of defatted beans or seeds of Simmondsia chinensis from the Simmondsiaceae family, intended for use in inducing stimulation of the expression of genes involved in the oxidative and cellular stress response (detox enzymes and oxygen free radical scavengers (ORS)) as well as for increasing the expression of genes involved in keratinocyte differentiation (SPRR2A, 2D, KRT1, IVL, TGM1), given that: SPRR2A and 2D correspond to small proteins released during the maturation or differentiation of keratinocytes and which are then taken up by transglutaminases at the level of the stratum corneum to form the corneal envelope surrounding the corneocytes, giving them sufficient rigidity to allow good cohesion and therefore an essential barrier effect as well as a beautiful appearance on the skin surface. KRT1 for Keratin 1 is a keratin and an intermediate filament of the cytoskeleton playing an important role in maintaining the skin barrier. IVL is the gene that produces Involucrin, which serves as a primer for the binding of other molecules of the corneal envelope. TGMlest is the gene that produces Transglutaminase 1, an enzyme that allows the polymerization of the different molecules that form the envelopes of corneocytes (involucrin, keratin 1, small SPRR-type proteins). The epidermis therefore sees its keratinocytes differentiate better, its horny envelopes form better, as a result of which the skin will be more beautiful on the surface, more resistant to the harmful effects of aging and presenting a better quality barrier effect.

[0053] Among all the disclosed plant extracts is Moringa oleifera, from the Moringaceae family, which has numerous and well-known properties when used as a whole, and particularly its oil obtained from its seeds. Indeed, Moringa oleifera oil is used in food but also for a wide variety of internal and external treatments, such as for treating acne and eczema. It has antimicrobial properties and is used in cosmetics to treat skin and hair.

[0054] Moringa oleifera of the Moringaceae family is a fast-growing tree that produces fruits in the form of long capsules arranged in diffuse or drooping clusters containing about thirty oily seeds and 3 wings each.

[0055] A patent application FR2310103 discloses the interest of water-soluble extracts of delipidated seeds of this plant in a cosmetically acceptable vehicle such as water, hydroalcoholic solutions, glycerol, which poses the problems listed above and which the present application solves.

[0056] More specifically, a composition comprising a water-soluble extract of defatted seeds of Moringa oleifera from the Moringaceae family for use in the treatment or prevention of the negative effects caused by skin aging, such as decreased detoxification and purification, a reduced capacity to combat oxidative stress and free radicals, increased localized fat deposits, a diminished barrier function, reduced intercellular cohesion, and impaired microbiota via the microbiome, all linked to under-expression of Glutathione peroxidase 2 (GPX2), Desmoglein 1 (DSG1), Glutamate-cysteine ​​ligase (GCLC), and keratin 1 (KRT1), or, conversely, to over-expression of Metalloproteinases 1, 3, and 10 (MMP 1, 3, 10) or of the Adam 19 proteinase (ADAM 19).

[0057] Indeed, Glutathione peroxidase 2 (GPX2) has a decreasing level of expression in senescent cells or cells whose aging has been induced by H2O2 compared with young cells. Desmoglein, on the other hand, is a desmosomal protein naturally encoded by the DSG1 gene, predominantly expressed in the outermost layers of the epidermis. It is responsible for the adhesive properties of the desmosomes, which act like snap fasteners, ensuring the cell-cell junction essential for the skin's barrier function and cohesion. Its production is also stimulated by this hydrophilic and water-soluble extract of Moringa oleifera seeds. Glutamate-cysteine ​​ligase (GCLC) plays a role in glutathione metabolism and biosynthesis, as well as in responding to oxidative stress and free radicals, ultimately influencing aging, acting in concert with GPX2 and KRT1. Keratin 1 (KRT1), a cytokeratin and intermediate filament of the cytoskeleton, plays an important role in maintaining the skin barrier, keratinization, and epidermal cell formation. Matrix metalloproteinase 1 (MMPI) is a gene encoding a protein that maintains the structure of chromosome 4, the overexpression of which is detrimental to cellular and tissue function and citing: Oncogenesis. 2017 Mar; 6(3): e301. doi: 10.1038 / oncsis.2017. The Adam 19 proteinase (ADAM 19) which is overexpressed in cases of obesity and localized adipocyte overload.

[0058] Among all the plant extracts disclosed is also Dialium guineense or Dialium cochinchinense from the Fabaceae family, rich in trace elements, which act as a food supplement to stimulate vitality and energy and are also used to increase lactation.

[0059] A patent application FR2310104 discloses the interest of water-soluble extracts of delipidated pulps of this plant in a cosmetically acceptable vehicle such as water, hydroalcoholic solutions, glycerol, which poses the problems listed above and which the present application solves.

[0060] And more specifically a water-soluble extract of delipidated pulp of Dialium guineense or Dialium cochinchinense of the Fabaceae family for the treatment or prevention of negative effects caused by under-expression of Insulin-like Growth Factor Binding Protein 3 (IGFBP3), Desmoglein 1 (DSG1) and chromosome 10 open rEDGing frame 99 (10orf99) or, on the contrary, in the context of over-expression of genes promoting skin problems such as Structural maintenance of Chromosome 4 (SMC4).

[0061] Indeed, the Insulin-like Growth Factor Binding Protein 3 (IGFBP3) has a decreasing level of expression in senescent cells or cells whose aging has been induced by H2O2 compared with young cells. Chromosome 10 open rEDGing frame 99 (10orf99) codes for peptides that enable the body's natural defense response against bacteria, particularly Gram-positive bacteria, as well as fungi. It regulates the pro-inflammatory response and participates in the skin barrier and the proper functioning of the microbiota via its microbiome. Desmoglein, on the other hand, is a desmosomal protein naturally encoded by the DSG1 gene, predominantly expressed in the outermost layers of the epidermis. It is responsible for the adhesive properties of the desmosomes, which act as snap fasteners, ensuring the cell-cell junction essential for the skin's barrier function and cohesion. Its production is also stimulated by this hydrophilic and water-soluble extract of Dialium guineense or Dialium cochinchinense pulp. Structural maintenance of Chromosome 4 (SMC4) is a gene encoding a protein that maintains the structure of chromosome 4, the overexpression of which is detrimental to cellular and tissue function.

[0062] The invention further relates to the cosmetic use of water-soluble extract of delipidated pulp of Dialium guineense or Dialium cochinchinense of the family of Fabaceae intended for use in the treatment or prevention of adverse effects caused by underexpression of Insulin-like Growth Factor Binding Protein 3 (IGFBP3), Desmoglein 1 (DSG1) and chromosome 10 open rEDGing frame 99 (10orf99) or, conversely, in the context of overexpression of genes promoting problems such as Structural maintenance of Chromosome 4 (SMC4).

[0063] The invention further discloses the cosmetic use of a water-soluble extract of delipidated pulp of Dialium guineense or Dialium cochinchinense of the Fabaceae family, intended to induce inhibition of the proliferation / division / progression processes of the cell cycle and a pro-differentiating effect by increasing the expression of genes involved in the process of epidermal maturation and differentiation (KLK7, SPRR1A, IB, 2A, 2D, CRABP2, TGM1, KRT10), given that: SPRR1A, IB, 2A and 2D correspond to a set of small proteins released during the maturation or differentiation of keratinocytes and which are then taken up by transglutaminases at the level of the stratum corneum to form the corneal envelope surrounding the keratinocytes, giving them sufficient rigidity to allow good cohesion and therefore an essential barrier effect as well as a beautiful appearance on the surface of the skin, KRT 7 and 10 for Keratin7 and Keratin 10 which are cytokeratins and intermediate filaments of the cytoskeleton playing an important role in maintaining the skin barrier, keratinization and epidermal co-formation.

[0064] TGM 1 is the gene that produces Transglutaminase 1, an enzyme that enables the polymerization of the various molecules that form the envelopes of corneocytes, such as keratins 7 and 10 and small SPRR-type proteins. The epidermis therefore sees its keratinocytes differentiate better, its horny envelopes form better, as a result of which the skin will be more beautiful on the surface, more resistant to the harmful effects of aging and presenting a better quality barrier effect.

[0065] Among all the disclosed plant extracts, Balanites aegyptiaca and the African Balanites roxburghii, both members of the Zygophyllaceae family, possess numerous and well-known properties when used as a whole, and particularly when its oil is used. Indeed, the oil of Balanites aegyptiaca or Balanites roxburghii, known as Soump oil in Senegal, is a medicinal oil rich in properties, used for a wide variety of external treatments. It exhibits, among other things, anti-inflammatory, antiviral, and antimicrobial actions and is used on the skin and hair.

[0066] A patent application FR2310106 discloses the interest of water-soluble extracts of defatted almonds of this plant in a cosmetically acceptable vehicle such as water, hydroalcoholic solutions, glycerol, which poses the problems listed above and which this application resolves.

[0067] The invention discloses the cosmetic use of water-soluble extract of defatted almonds of Balanites aegyptiaca or African Balanites roxburghii of the Zygophyllaceae family intended for use in the treatment or prevention of decreased cohesion of epidermal cells, the skin barrier effect, its homeostasis, protection against the effects of pollution and dehydration, regulation of desquamation, skin surface suppleness, the functioning of skin mechanoreceptors and its cytoskeleton, and increased propagation of possibly damaged skin cells, characterized in that aqueous, hydroethanolic, or hydroglycerin extracts are capable of improving the expression of Paxillin (PXN).of protein 53 (p 53) and Heparin-Binding EGF-like Growth Factor (HBEGF) of skin cells and to reduce those of Nima-related Kinase 2 (NEK2) and Insulin-like Growth Factor binding protein 5 (IGF5) optimized by genome-wide gene expression analysis (36,000 transcribed genes and variants) of normal human epidermal keratinocytes and by DNA microarray hybridization.

[0068] Indeed, praxillin also allows for the fixation, propagation, and migration of cells, such as during epidermal differentiation, ensuring the maturation of keratinocytes into comeocytes. It is often said that without their anchors, the focal adhesions organized around praxillin, cells would slip. Praxillin also plays a role, thanks to these focal adhesion structures, in the cohesion of epidermal cells, the skin barrier effect, protection against the effects of pollution and dehydration, the regulation of desquamation, and the skin's surface elasticity. Protein 53 (p53) regulates the fate of damaged cells by preventing them from propagating. Heparin-Binding EGF-like Growth Factor (HBEGF) promotes skin cell homeostasis and protects skin stem cells, including hair cells, thus promoting their regrowth, allows firming effects without risk of fibrosis and has promelanin-like effects. Nima-related kinase 2 (NEK2), a centrosomal protein kinase, increases in cancers, and much research is being conducted to find NEK2 inhibitors: Cell Cycle. 2016; 15(7): 895-907. doi: 10.1080 / 15384101.2016.1152430. Insulin-like growth factor binding protein 5 (IGF5), on the other hand, is capable of inducing senescence (Mol Biol Cell. (2007) 18:4543-52. doi: 10.1091 / mbc.e07-03-0280). Clearly, preventing skin cells from expressing too much NEK2 and IGF5 is highly beneficial for maintaining healthy skin.

[0069] Among all the disclosed plant extracts, African Carapa procera, from the Meliaceae family, has numerous and well-known properties when used as a whole, and particularly its oil. Indeed, Carapa procera oil, called Touloucouna oil in Senegal, is a medicinal oil rich in properties, used for a wide variety of internal and external treatments. It reduces skin inflammation and is effective against psoriasis, scalp problems, and insect bites, as well as in cases of rheumatism, ringworm, and ulcers. It has even been the subject of an international application WO2009155497A1.

[0070] A patent application FR2310110 discloses the interest of water-soluble extracts of delipidated almonds of this plant in a cosmetically acceptable vehicle such as water, hydroalcoholic solutions, glycerol, which poses the problems listed above and which the present application solves.

[0071] And more specifically, a water-soluble extract of delipidated almonds of African Carapa procera of the Meliaceae family is disclosed for the treatment or prevention of hyperpigmentation of healthy skin and its skin aging, particularly when skin cells do not synthesize enough IGFBP-3 (Insulin-like Growth Factor Binding Protein-3) as during their aging or senescence, or when there is an interest in reducing their synthesis of kinectin 1 (KTN1), LUC7-like (LUC7L3), golgin A or Calpastatin (CAST), genes promoting the synthesis of melanins and therefore epidermal hyperpigmentation.

[0072] Indeed, IGFBP-3 is a true marker of aging that decreases when senescence is induced in skin cell culture by hydrogen peroxide (H2O2) compared to cells that remain young. Therefore, there is a cosmetic benefit to increasing its expression in a physiological manner. Kinectin-1 (KTN1), in association with endogenous kinetin, is essential for the maturation and migration of melanosomes within the dendrites of the melanocyte tubulin before the cell transfers its melanosomes to keratinocytes, a process responsible for pigmentation. Reducing kinectin-1 by up to 90% will allow for localized and cosmetic reduction of pigmentation. Reducing the expression of LUC7L3, a splicing factor, the apoptotic process, and Golgin A, which acts on tubulins, also contributes to this reduction in pigmentation. This is achieved through contact with various superficial parts of the human body, thus providing a cosmetic effect. Similarly, the decrease in calpastatin expression, with the signal intensity dropping from 33.24 to 0.09 (more than a 90% reduction in the expression of this gene), inhibits calpain, which is involved in alpha-MSH-induced melanogenesis. Calpain acts on tyrosinase, a target of many cosmetics seeking to reduce skin pigmentation, as demonstrated by Ohguchi K et al., "Involvement of calpain in melanogenesis of mouse B16 melanoma cells." (Mol.) Cell Biochem. 2005 Jul;275(l-2): 103-7. doi:10.1007 / sll010-005-1081-0. PMID: 16335789.

[0073] The invention further discloses the cosmetic use of water-soluble extract of delipidated almonds of African Campa procera of the Meliaceae family intended for use in the treatment and / or prevention of hyperpigmentation and skin aging characterized in that the aqueous, hydroethanolic or hydroglycerin extracts are capable of improving the expression of IGFBP-3 and reducing those of KTN1, LUC7L3 of golgin A or CAST.

[0074] The invention discloses the non-therapeutic cosmetic use of a composition to improve hyperpigmentation of healthy skin and its aging, particularly when skin cells do not synthesize enough IGFBP-3 (Insulin-like Growth Factor Binding Protein-3) as during their aging or senescence, or when there is an interest in reducing their synthesis of kinectin 1 (KTN1), LUC7-like (LUC7L3), golgin A or Calpastatin (CAST), genes promoting melanin synthesis and therefore epidermal hyperpigmentation.

[0075] There is therefore a real need for plant extracts that can solve all these problems, for example, in smaller quantities, with real and lasting effectiveness that respects our health and the environment. This allows for the inclusion of all the water in a cosmetic formulation when calculating the percentage of natural ingredients in a formula. This also reduces the volume to be transported and can be used in all cosmetics, including solid products.

[0076] Quite surprisingly, the applicant realized that with only 10 plants and knowledge of the genes that each stimulates or inhibits, it is possible to create 1023 combinations to enhance the effects of one or more genes or to act on a larger number of genes. Surprisingly, for the ten plants used as examples in this description, preferably ground into a fine powder of semolina, it is possible to create up to 1023 different and multifunctional combinations! Such a large number of combinations is only possible thanks to the powdery structure of the defatted plant parts, whether pressed together or separately, and would be impossible for formulating a cosmetic composition from extracts solubilized in one or more liquid solvents.

[0077] All of this makes it possible to create a multifunctional cosmetic composition whose aqueous phase is produced extemporaneously from one or more semolina-type powders derived from plant parts such as fruits or fruit parts such as seeds, almonds, beans, their defatted pulps, and also their tubers, also defatted by several cold pressings, allowing for a possible 2n-1 combination of semolina (or as used to allow the inclusion of a equation in a power: 2An-l), with n the number of defatted oilseed cakes used, as well as a cosmetically acceptable vehicle.

[0078] The invention therefore also relates to a cosmetic composition, said semolina being made by mixing these plant parts before or after cold pressing one to three times with a die adjusted to obtain a homogeneous and regular lipid-free roll, then by milling in a hammer mill followed by sieving, all these steps being preceded or followed by drying in an oven for 5 hours at a temperature between 50 and 60°C, all of which makes it possible to obtain semolina with a particle size between 100 µm and 1000 µm and ideally between 150 µm and 600 µm

[0079] Consequently, also a cosmetic composition, said semolina being made from a selection of plants after studies of their properties optimized by the analysis of gene expression on the scale of the whole human genome (36,000 transcribed genes and variants) of normal human epidermal keratinocytes and by hybridization on DNA microarrays or cDNA in order to choose either to reinforce a retained effect or to complement one or more effects with others in order to obtain a multifunctional semolina and which may be included in the following list of plants without this list being exhaustive:

[0080] -Baobab, Adansonia digitata of the Malvaceae family

[0081] -Djar, African Xylopia aethiopica of the Annonaceae family

[0082] -Hibiscus, Hibiscus sabdariffa of the Malvaceae family

[0083] -Jojoba, Simmondsia chinensis of the Simmondsiaceae family

[0084] -Loofah, Luffa aegyptiaca or Luffa cylindrica of the Cucurbitaceae family

[0085] -Moringa, Moringa oleifera of the Moringaceae family

[0086] -Solom, Dialium guineense or Dialium cochinchinense of the Fabaceae family

[0087] -Souchet, Cyperus esculentus of the Cyperaceae family

[0088] -Soump, Balanites aegyptiaca or Balanites roxburghii of the Zygophyllaceae family

[0089] -Touloucouna, Carapa procera of the Meliaceae family

[0090] Each of these plants must be standardized with respect to its maximum possible non-cytotoxic concentration on culture of normal human keratinocytes

[0091] In the context of the invention, this refers to a cosmetic composition, where said defatted extract, reduced to a semolina-like powder and then dried, comes from a single plant or from a mixture of several plants ranging from 2 to 10 in varying proportions. This multifunctional mixture can be prepared on demand by the supplier or by the manufacturer itself, thus ensuring confidentiality. The number of different possible semolinas is 2¹⁰, or 10²³ (10²⁴ - 1 = 10²³ since 2 to the power of 10 equals 10²⁴). Furthermore, the composition contains no preservatives. which may interact negatively with the rest of the formula, the environment and the health of the end user of this composition.

[0092] Advantageously, the cosmetic composition in which said multifunctional delipidated extracts from a single plant or mixtures of plants reduced to a semolina-type powder and then dried allows their incorporation by the formulator directly into the aqueous phase of the formula extemporaneously, at a concentration of 0.5% to 5% and at a temperature between 20°C and 40°C for 1 to 4 hours and followed by decantation for 1 to 2 hours and recovery of the supernatant after centrifugation or not and its filtration at 0.2 µm.

[0093] The invention also relates to a composition where said multifunctional delipidated extracts from a single plant or from mixtures reduced to semolina-type powder and then dried allow their incorporation by the formulator directly into the aqueous phase of the formula extemporaneously can be decolorized by the addition of 0.1% and 3% of activated carbon directly into the aqueous phase by the formulator between the start of incorporation and that of filtration or included in the semolina during its manufacture.

[0094] The invention further relates to a cosmetic composition where said delipidated extracts from a single plant or mixtures of several plants reduced to a semolina-type powder and then dried allow their incorporation by the formulator directly into the aqueous phase of the formula extemporaneously, at a concentration of 1 to 5% and at a temperature between 20°C and 40°C for 1 to 4 h followed by the use of this complete aqueous phase in the rest of the formulation including therefore the fibrous pellet of the delipidated extracts in order to allow an additional scrubbing and exfoliating effect.This fibrous pellet can also be separated from the aqueous phase and then dried before being incorporated at another stage of the formulation of the composition, for example in the oily phase or even to be used as an exfoliant or scrub (still commonly called, from the anglicism, scrub) in a different composition, complementary to the first or not.

[0095] The invention also relates to a cosmetic composition in which said multifunctional delipidated extracts from a single plant or from mixtures reduced to a semolina-like powder and then dried allow for transport in a smaller volume than extracts already solubilized in their solvents, with significant economic advantages as well as in terms of respecting our planet. This advantage is all the more pronounced when the plants have a different origin and are located far from the place where the composition is formulated. This dry semolina form, easy for the formulator to use, also has the advantage of eliminating the need for preservatives and therefore favourable to more organic or more natural compositions for the respect of the skin health of the end consumer as well as the environment.

[0096] Advantageously, the composition in which said multifunctional delipidated extracts from a single plant or mixtures reduced to a semolina-like powder and then dried allows their incorporation by the formulator directly into the aqueous phase of the formula extemporaneously makes it easier to obtain and allows for more labels by making it possible to consider the entire aqueous phase of the composition, which may exceed 50%, as being of organic or natural origin instead of only 0.5% to 5% of the extract if it were already solubilized and used conventionally.

[0097] The invention therefore relates to a method for developing semolina-type powder with a particle size between 100 µm and 1000 µm and ideally between 150 µm and 600 µm from 10 delipidated extracts of a single plant or mixtures of different plants, reduced to powder and then dried for testing on the whole human genome, by analyzing gene expression at the whole genome level (36,000 transcribed genes and variants) of normal human epidermal keratinocytes and by hybridization on DNA microarrays, also called cDNA arrays.in order to catalog all the genes either stimulated or inhibited at maximum non-cytotoxic doses and ultimately allow the selection of plant combinations either acting on the same gene(s) for maximum effect or acting on different genes for the broadest possible activity, thus enabling, with a single semolina, more powerful or more complete multifunctional effects, clearly illustrating the "less is more" approach of the English phrase "less is more," dear to skinlimism, and allowing simple extemporaneous incorporation into the aqueous phase of a cosmetic composition.

[0098] Examples are given below without being limiting in order to illustrate the invention.

[0099] Example 1. Test and cytotoxicity results on normal human epidermal keratinocytes (NHEK) carried out in comparison on 10 semolina extracts obtained from delipidated plant parts.

[0100] Incubation time 24 h

[0101] NHEK cell type in test medium

[0102] Evaluation: Reduction of MTT and morphological observations under the microscope.

[0103] Parameter: At the end of the treatment, the cells were incubated in the presence of MTT (tetrazolium salt), the transformation of which into blue formazan crystals is proportional to the activity of succinate dehydrogenase (mitochondrial enzyme). After cell dissociation and solubilization of the formazan by the addition of DMSO, the optical density (OD), representative of the number of living cells and their metabolic activity was measured with a spectrophotometer at 540 nm (VERSAmax, Molecular Devices).

[0104] Results of the determination of the maximum non-cytotoxic dose:

[0105] -Baobab, Adansonia digitata: 1.66 mg / ml

[0106] -Djar, Xylopia aethiopica: 0.1 mg / ml

[0107] -Hibiscus, Hibiscus sabdariffa: 1 mg / ml

[0108] -Jojoba, Simmondsia chinensis: 0.33 mg / ml

[0109] -Loofah, Luffa aegyptiaca: 0.33 mg / ml

[0110] -Moringa, Moringa oleifera: 0.01 mg / ml

[0111] -Solom, Dialium guineense: 0.66 mg / ml

[0112] -Cyperus esculentus: 0.3 mg / ml

[0113] -Soump, Balanites aegyptiaca: 0.033 mg / ml

[0114] -Touloucouna, Carapa procera: 0.066 mg / ml

[0115] These results make it possible to compare these delipidated extract powders and to test them comparatively in effectiveness, for example in DNA microchip testing on the whole human genome.

[0116] These results also allow for comparable associations of powders from the point of view of effectiveness.

[0117] Example 2. Whole human genome study from normal human epidermal keratinocytes The biological model: Third-pass normal human epidermal keratinocytes (NHEK) cultured at 37°C and 5% CO2. Culture medium supplemented with EGF at 0.25 ng / ml and EP at 25 µg plus gentamicin 25 µg. The assay medium consisted of SFM keratinocytes with only gentamicin 25 µg / ml. Experimental conditions: Keratinocytes were seeded in 24-well plates and cultured in culture medium for 24 hours, then in test medium for an additional 24 hours. The medium was then replaced with test medium containing or not (control) the compounds under investigation, and the cells were incubated for 24 hours. All experimental conditions were performed in triplicate (n=3). At the end of incubation, the culture supernatants were removed and the cell mats were rinsed with a PBS solution. The plate was immediately frozen dry at -80°C. Prior to extraction, the culture replicates were pooled. Total RNA from each sample was extracted using TriPure Isolation Reagent® according to the protocol recommended by the supplier. The quantity and quality of RNA were assessed by capillary electrophoresis (Bioanalyzer 2100, Agilent). The synthesis of biotinylated antisense RNAs (aRNAs) was carried out using the "GeneChip 3'IVT Express" kit (Affymetrix®). For each biotinylated RNA sample, an electrophoretic profile was performed (Bioanalyzer 2100, Agilent) before and after fragmentation. The hybridization of labeled and fragmented RNAs on the Affymetrix® U219 chip (36,000 transcripts and variants) was carried out on the GeneAtlas™ fluidics Affymetrix ® hybridization station for 20 hours at 45 °C. The U219 chips were then scanned using the GeneAtlas™ Imaging station (Affymetrix® - 2 pm resolution) to generate signal intensity data as shown in the result examples below. Signal intensity data were normalized using Expression Console software (Affymetrix®), based on the RMA algorithm. Quality control of the labeling and hybridization was then performed. Quality controls of the hybridization and labeling steps validated the experimental process Once normalized with Expression Console software, the data were transferred and formatted in a Microsoft Excel file. Calculations and filters have been added to these files to sort the data and facilitate its use. The "fold change" thresholds or rate of change (value corresponding to the ratio: signal intensity value of a probe corresponding to the treated sample / signal intensity value of a probe corresponding to the control) were defined and applied to the normalized data. The results file is given below for 72 of the most interesting genes from a skin perspective, with Stimulate when the gene is stimulated by the semolina of the corresponding plant and Inhibit when, on the contrary, the gene is inhibited by its semolina: ëEOULOUCOUN ^SOUMP SOUCHE ■ SOLOK! MORING^ ■ LQQEAH JOJOBA DJAR HIBISCUS 8AOBA ANGPTL4 Stimulates Stimulates AKR1C1 Stimulates Stimulates Stimulates CLDN4 Stimulates CYP1B1 Stimulates Stimulates fGFBP3 Stimulates Stimulates Stimulate» Stimulates Stimulates IGFBP5 inhibits Inhibits Inhibits Inhibits Inhibits SPRR1A Stimulates Stimulates Stimulate SPRR18 Stimulates Stimulates SPRR2A Stimulates Stimulate Stimulate Stimulate Stimulate SPRR2D Stimulates Stimulate Stimulate Stimulate Stimulate SPRR2E Stimulates MMPI Inhibits Inhibits Inhibits Inhibited MMP10 Inhibits Inhibits Inhibits Inhibits Inhibitors MMP3 Inhibits Inhibits Inhibits Inhibited Inhibited Inhibits MMP? Inhibits Inhibits Inhibits Inhibits CDSN Stimulated oJUN Inhibits Inhibits CPTIA Stimulates CASP14 Stimulates Stimulates CAST Inhibits Inhibits Inhibits CRABP2 Stimulates Stimulates CTGF Inhibits CXCL1 Stimulates Stimulates CWorf99 Stimulates Stimulates Stimulates S100A7 Stimulates Stimulates Si 09 AB Stimulates Stimulates S100A9 Stimulates Stimulates Stimulates KLK10 Stimulates Stimulates KLK7 Stimulates Stimulates Stimulates KLK8 Stimulates KLK9 Stimulates KRT1 Stimulates Stimulates Stimulate Stimulate Stimulates KTN1 InhibitsLCN2 Stimulates Stimulates LUC7L3 Inhibited Inhibited DCN Stimulates Stimulates DEFB1 Stimulates Stimulates Stimulates DMKN Stimulates DSC1 Stimulates Stimulates Stimulates DSG1 Stimulates Stimulates Stimulates Stimulate Stimulate Stimulate EREG Stimulates Stimulates Stimulates FLG Stimulates GCLC Stimulates Golgin A Inhibits Inhibits GPX2 Stimulates Stimulates Stimulates HBEGF Stimulates IL33 Inhibits Inhibits IVL Stimulates Stimulates MX2 Stimulates Stimulates NEK2 Inhibits Inhibits Inhibits Inhibits Inhibits Inhibits Nrf2 Stimulates OCLN Stimulates P53 Stimulates PUN2 Stimulates PXN Stimulates Stimulates SBSN Stimulates Stimulates SCEL Stimulates Stimulates SERPÎNB1 Stimulates Stimulates Stimulates SERPÎNB2 Stimulates SERPfNB3 Stimulates Stimulates Stimulates ADAM B Stimulates Stimulates Stimulates ADAM 19 Inhibits Inhibits Inhibits Inhibits Inhibits SMC4 Inhibits SOD2 Stimulates Stimulates STMN3 Inhibits TGM1 Stimulates Stimulates Stimulated TGM2 Inhibits Inhibits Inhibits TNG Inhibits Inhibits TXNRD1 Stimulates Stimulates WNT10A Stimulates Inhibited WNT4 Stimulates Inhibits Stimulates Stimulates XAF1 Inhibits Inhibits Inhibits Inhibits Inhibits Inhibits STIMULATION KNHWIO ■J 315'227? 005 / 502 009 / 021 160 / 324021 / 308 001 / 011 mœei 070,-365 057 / 1SÎ 133 / 142 Genes " £ten éfiOULOUCOUN SiSÔUMP strain: ' SOLOM MORING, . LOOFAH JOJOBA DJAR HIBISCUS BAGBA

[0118]

[0119]

[0120]

[0121]

[0122]

[0123]

[0124] In the penultimate line the total number of stimulated and inhibited genes are indicated, for example for Baobab 138 genes are significantly stimulated and 142 inhibited. In the rest of this description, we will refer to this table as the results of the effects of defatted vegetable semolina on the human genome. The following abbreviations are used in this results file: Abréviation gène s Nom complet du gèr e Abréviations gènes (su complet gènes (su ADAM 8 metaJiupépûdase Adam 8 LCN2 hpocaitn ADAM 19 rnÊtelippÊptida^é Adam 13 LUC7L3 Luc7- iikv3 AKR1C1 atâokefcxsductase 1 MMPI mstrix meiaiburatoinase: 1 ANGPTL4 MMP10 matrix 10 CASP14 caspase 14 MMP3 maùix melatopr^ CAST cslpaslahr: MMP7 matrix 7 CDSN MX2 niyxoyirûs résistance c-JUN facteur Varsscription duo NEK2 Ntma folâled kinase 2 CLDN4 Nrf2 mj N [2 riwctear faotor CPT! A OCLN xi H d CRABP2 CSÎkfAI reDXhC àc:d biddins pNitem 2 P53 - 1 ) HJ GTGF coriftaclive tissu© growîtî tacæf PLIN2 F 1'4 " " CXCL1 cnemckine ligand > PXN P hn CŸP1B1 cytochrçma FviSü fomity 1 S100A7 19i - rr UfTs btn-ding protein A7 C10otf99 open teading 99 SI 00 AB S1 di : il ot b;-'ding pfotein AS DCN dacodn S100A9 Si 00 IWing pmtein A3 DEFB1 bela-tfefensip i SBSN süprè&asks DMKN dermokme SCEL Svielim DSC1 desmocoSin- i SERPSNB1 serpin pepticasa infàpter B' DSG1 de^mçgtei:'! 1 SERPÎNB2 set-pin inWfrN' S2 EREG epiffigülin SERPfNB3 sern;n tnhsudot 83 FLG fteggrin SMC4 p-lructihM maintenance ùf chrom 4 GCLC g I utàmàte -cys tein ? i gase SOD2 st:p2n» yce dissout asc- Golqin AA SPRR1A siTiasl groiine rich n GPX2 glutathion parnxydase SPRR1B smati jwine rich ptor^n HBËGF h&pqnn binding EGF :jka grpwtb fact< SPRR2A smaii o-rpiitte rich ntQfeiii IGFBP3!:;ke arqwfh factor 3 SPRR2D smaîl orc-irte rich pmtein IGFBP5 in ^itiïna üke àrcwlMactor 5 SPRR2E small üroîiue dch proton IL33 interteukin STMN3 (VL involucrtn TGM1 t^sgiidaminase j KLK10 kaiBkr^'n <e«aèGd klna&a fO TGM2 KLK7 Ksii-ive?eia&d kinase 7 TNC fenasun C KLK8 kalliKfoin-rëiated kinase 8 TXNRD1 îhip&ooxtn rectuctaAe 1 KLK9 kailiKr&in-^iated kinase S WNT10A ’MngfesÈ type lüA KRT1 kératin 1 WNT4 wingfsss type:4 KTN1 kwiécun 1 XAF1 KIAP assœtaled factor < ; It is therefore possible to compose your choice of combination of plant powders for multiple effects or also for reinforced effects. More than 1000 combinations are possible from 10 plants. For example, if we want to enhance the cosmetic effect on involucrin, a protein of the stratum corneum located on the very surface of the skin and in direct contact with a cosmetic that would be applied to it, the combination of Baobab seed powder and Jojoba bean powder is ideal, as these tables indicate. However, it is interesting to complement the numerous effects of Baobab with stimulation of the nuclear factor 2 pathway, Nrf2, to block the effect of stress on the skin, and of the genes for Occludin, Ocln, proteins of epidermal tight junctions, and perilipin 2, Plin2, which is very useful for a topical slimming product. Therefore, combining it with hibiscus seed powder is recommended, also following the indications in these tables.

[0125] It may also be useful to classify in the plants versus genes table the intensities of stimulation or inhibition into several levels of effectiveness each, ideally 3, in order to more easily identify the associations of interest. It is thus easier to be able to properly evaluate the interest of associations of semolina inhibiting certain genes with other semolina stimulating other genes.

[0126] Example 3 Use of these powders for the formulation of cosmetic compositions.

[0127] Multifunctional delipidated extracts from a single plant or mixtures of several plants reduced to a semolina-type powder and then dried are used by the formulator directly in the aqueous phase of the formula extemporaneously, at a concentration of 0.5% to 5% and at a temperature between 20°C and 40°C for 1 to 4 hours and followed by decantation for 1 to 2 hours and recovery of the supernatant after centrifugation or not and its filtration at 0.2 pm.

[0128] This environmentally friendly method, which simplifies formulation while avoiding the use of preservatives to preserve plant extracts, also allows the entire aqueous phase of the formula to be claimed as a natural or organic ingredient and its percentage to be increased in the final formula.

[0129] For example, in the case of an emulsion or cosmetic composition, four implementations are given below, without being exhaustive, and clearly demonstrating the advantage of being able to declare the water in the aqueous phase as organic or natural:

[0130] According to a first embodiment with SEV for semolina of plant extracts of the invention, the composition comprises: - Acrylate C10-30........................................................0.50 g - Arginine............................................................0.001g - Glycerin..................................................................................1.00 g - Alcohol..................................................................2.00 g - Carbomer................................................................................0.126 g - EDTA..............................................................................................0.005 g - Preservative......................................................................0.867 g - Organic Carapa Oil..................................................................0.5 g - Hydrogenated lecithin.....................................................0.09 g - Hyaluronic acid....................................................................0.20 g - TEA 99%...................................................................................0.62 g - Colorings........................................................................0.0002 g - SEV at 1 g in aqueous phase..................................................93.89 g The percentage of natural or organic extract in the formula increases here from 1.7% (1 g of SEV + 0.5 of organic carapa oil) to 94.39% (93.89+0.5)

[0131] According to a second embodiment of the invention, the composition comprises, for an oil-in-water emulsion, always with SEV for semolina of plant extracts: - Liquid paraffin.................................................6 g - Liquid lanolin................................................................3 g - Arlacel 165................................................................6 g - Tween 60...................................................................2 g - Cetyl alcohol................................................................1.2 g - Stearic acid.................................................2.5 g - Arginine........................................................................0.5 g - Volatile silicone oil...................................................10 g - Triethanolamine................................................................0.1 g - Preservative....................................................................0.3 g - Hyaluronic acid.......................................................0.5 g - SEV at 5g in aqueous phase..........................................67.9g

[0132] The percentage of natural or organic extract that may be claimed for this oil-in-water emulsion increases here from 5% to 67.9%

[0133] According to a third embodiment of the invention, the composition comprises, for a W / O emulsion, always with SEV for semolina of plant extracts: - Protein.......................................................................19g - Organic glycerin..............................................................................3 g - Vaseline oil.........................................................................8 g - Mg sulfate.............................................................................0.5 g - Hyaluronic acid.................................................................0.02 g - Preservative............................................................2 g - SEV at 2 g in aqueous phase............................................ 67.48 g

[0134] The % of natural or organic extract that may be claimed for this W / O emulsion increases here from 5% (2% of VSE + 3% of glycerin) to 70.9% (67.48 + 3)

[0135] According to another embodiment of the invention, the composition comprises, for an O / W gel emulsion, always with SEV for semolina of plant extracts: - Carbopol 981 .........................................................0.6 g - Ethyl alcohol..........................................................................15 g - Volatile silicone oil...............................................................3 g - Organic Jojoba oil........................................................................7 g - Preservative............................................................0.3 g - Perfume...................................................................0.4 g - SEV 1.5 g in aqueous phase.............................................73.7 g

[0136] The % of natural or organic extract that may be claimed for this gel emulsion increases here from 8.5% (1.5% of SEV + 7% of jojoba oil) to 80.7% (73.7 + 7)

[0137] According to another embodiment of the invention, the composition comprises, for a liposome cream, always with SEV for semolina of plant extracts: - Cetyl alcohol.............................................................................4 g - B-sitosterol...................................................................................4 g - Dicetyl phosphate................................................................................0.5 g - Preservative..............................................................................0.3 g - Carbopol 981 ...................................................................0.2 g - Triethanolamine.........................................................................0.2 g - Phospholipid........................................................................................0.05 g - SEV at 2.5% in aqueous phase................................................90.75g

[0138] The percentage of natural or organic extract that may be claimed in the formula increases here from 2.5% to 90.75%.

[0139] Example 4. Use of the tables in Example 2 and the results of human genome studies to select mixtures of plant extracts and in vivo testing method on end-user cosmetic compositions

[0140] After selecting from the table of results of the effects of defatted vegetable semolina on the human genome and for example that described in example 2 and preparing a cosmetic composition the latter can be tested in vivo for example by the technique of unstructured analog scales in order to confirm in vivo the effects revealed in vitro.

[0141] Self-assessment analog scale efficacy test on skin firmness after 4 weeks of daily use. Example of the effect on skin firmness.

[0142] These scales are self-assessment scales. They only measure intensity. I. The Visual Analogue Scale (VAS) This is the most widely used and reliable. It consists of a straight line 100 millimeters long. At one end is indicated: no effect, at the other: maximum effect. The subject places a mark between these two ends according to the effect felt at a given time. In practice, it is a small plastic ruler with a slider on one side, which is moved by the subject, and millimeter graduations on the other, which are read by the person conducting the study. It was developed for pain assessment by Huskisson in 1974.

[0143] Visual Analog Scale (VAS) Patient instructions: We suggest you use a kind of thermometer to measure the condition of your skin at a given time, before and after treatment with the cosmetic product, which allows you to compare its effectiveness. The condition of your skin at a given time and for a given property, such as firmness, can be defined by a line drawn on the scale as in the example below:

[0144] Skin not firm IVI maximum skin firmness

[0145] One end corresponds to minimum firmness. The closer the line is to this end, the lower the firmness. The other end corresponds to maximum firmness. The closer the line is to this end, the higher the firmness.

[0146] Other parameters can be studied in the same study; it is sufficient to add a scale for each property to be studied, for example, wrinkles, hydration, skin radiance, etc. The advantage of this methodology is that it allows studies to be carried out on parameters for which no measuring device exists and avoids the numerous artifacts associated with such devices.

[0147] Results obtained with this protocol for an association in the aqueous phase of 1% Baobab semolina and 1% Hibiscus semolina (SBH) according to the cream to the following liposomes:

[0148] - Cetyl alcohol.............................................................................4 g - B-sitosterol...................................................................................4 g - Dicetyl phosphate................................................................................0.5 g - Preservative..............................................................................0.3 g - Carbopol 981 ...................................................................0.2 g - Triethanolamine.........................................................................0.2 g - Phospholipid........................................................................................0.05 g - SBH at 2% in aqueous phase...................................................90.75g

[0149] The test involved 25 healthy volunteers aged 35 to 45 years for 4 weeks with an evaluation by these analog scales at T0 before the use of this liposome cream and at T 28 after the last day of application.

[0150] Missing Parameter N Average Std Dev SEM

[0151] Firmness Before 25 0 4.832 1.855 0.371

[0152] Firmness After 25 0 6.152 1.630 0.326

[0153] Difference 25 0 1.320 1.377 0.275

[0154] As the results show a normal distribution (P = 0.388) a paired t-test could be performed.

[0155] t = -4.791 with 24 degrees of freedom. (P = <0.001)

[0156] The confidence interval is 95% with a mean difference of -1.889 to -0.751

[0157] The difference between before and after treatment is greater than that which would be caused by chance; therefore, there is a statistically significant difference (P = <0.001)

[0158] Alpha power of the test performed = 0.050: 0.998

[0159] Under experimental conditions and after daily application for 4 weeks of this liposome cream, skin firmness was significantly improved by 27%.

Claims

Demands

1. Multifunctional cosmetic composition whose aqueous phase is made extemporaneously from one or more semolina-type powders from plant parts such as fruits or fruit parts such as seeds, almonds, beans, their delipidated pulps and also their tubers also delipidated by several cold pressings and allowing 2n-l possible combinations of semolina, with n the number of delipidated press cake semolinas used, as well as a cosmetically acceptable vehicle.

2. Cosmetic composition according to claim 1, said semolina being produced by mixing these plant parts before or after cold pressing one to three times with a die adjusted to obtain a homogeneous and regular lipid-free roll, then milling in a hammer mill followed by sieving, all these steps being preceded or followed by oven drying for 5 hours at a temperature between 50 and 60°C, the whole process allowing the production of semolina with a particle size between 100 µm and 1000 µm and ideally between 150 µm and 600 µm

3. Cosmetic composition according to claims 1 and 2, said semolina being made from a selection of plants after studies of their properties optimized by the analysis of gene expression at the scale of the whole human genome (36,000 transcribed genes and variants) of normal human epidermal keratinocytes and by hybridization on DNA microarrays or cDNA in order to choose either to reinforce a retained effect or to complement one or more effects with others in order to obtain a multifunctional semolina and which may be included in the following list of plants without this list being exhaustive: -Baobab, Adansonia digitata of the Malvaceae family -Djar, Xylopia aethiopica africana of the Annonaceae family -Hibiscus, Hibiscus sabdariffa of the Malvaceae family -Jojoba, Simmondsia chinensis of the Simmondsiaceae family -Loofah, Luffa aegyptiaca or Luffa cylindrica of the Cucurbitaceae-Moringa family,Moringa oleifera of the family Moringaceae -Solom, Dialium guineense or Dialium cochinchinense of the family Fabaceae, -Cough, Cyperus esculentus of the Cyperaceae family -Soump, Balanites aegyptiaca or Balanites roxburghii of the Zygophyllaceae family -Touloucouna, Carapa procera of the Meliaceae family Each of these plants must be standardized with respect to its maximum possible non-cytotoxic concentration in culture of normal human keratinocytes

4. Cosmetic composition according to claims 1 to 3, wherein said delipidated extract reduced to semolina-type powder and then dried comes from a single plant or from a mixture of several plants from 2 to ten in proportions which may be different, this multifunctional mixture being able to be made on demand by the supplier or by the manufacturer himself thus guaranteeing confidentiality, the number of different semolinas possible being 210-l or 1023 as well as the absence of any preservative which may interact negatively with the rest of the formula, the environment and the health of the end user of this composition.

5. Cosmetic composition according to claims 1 to 4 wherein said multifunctional delipidated extracts from a single plant or mixtures of plants reduced to a semolina-type powder and then dried allow their incorporation by the formulator directly into the aqueous phase of the formula extemporaneously, at a concentration of 0.5% to 5% and at a temperature between 20°C and 40°C for 1 to 4 hours and followed by decantation for 1 to 2 hours and recovery of the supernatant after centrifugation or not and its filtration at 0.2 µm.

6. Cosmetic composition according to claims 1 to 5 wherein said multifunctional delipidated extracts from a single plant or mixtures reduced to semolina-type powder and then dried allow their incorporation by the formulator directly into the aqueous phase of the formula extemporaneously can be decolorized by the addition of 0.1% and 3% activated carbon directly into the aqueous phase by the formulator between the start of incorporation and that of filtration or included in the semolina during its manufacture.

7. Cosmetic composition according to claims 1 to 6, wherein said delipidated extracts from a single plant or mixtures of several plants are reduced to a semolina-type powder and then dried

8.

9.

10. This allows the formulator to incorporate them directly into the aqueous phase of the formula on the spot, at a concentration of 1 to 5% and at a temperature between 20°C and 40°C for 1 to 4 hours. This is followed by the use of this entire aqueous phase in the rest of the formulation, including the fibrous pellet of the delipidated extracts, to provide an additional scrubbing and exfoliating effect. This fibrous pellet can also be separated from the aqueous phase and then dried before being incorporated at another stage of the formulation, for example, into the oil phase, or even used as an exfoliant or scrub in a different composition, whether complementary to the first or not. Cosmetic composition according to claims 1 to 7, wherein said multifunctional delipidated extracts from a single plant or mixtures reduced to a semolina-like powder and then dried allow for transport in a smaller volume than extracts already solubilized in their solvents, with significant economic advantages as well as environmental benefits. This advantage is even more pronounced when the plants originate from a different and distant location from the formulation site. This dry semolina form, easy for the formulator to use, also has the advantage of eliminating the need for preservatives, thus favoring more organic or natural compositions that respect the health of the end consumer's skin and the environment.Cosmetic composition according to claims 1 to 8 wherein said multifunctional delipidated extracts from a single plant or mixtures reduced to a semolina-type powder and then dried allow their incorporation by the formulator directly into the aqueous phase of the formula extemporaneously allows for easier obtaining and more labels by allowing the entire aqueous phase of the composition, which may exceed 50%, to be considered as being of organic or natural origin instead of only 0.5% to 5% of the extract if it were already solubilized and used conventionally. Method for developing semolina-type powder with a particle size between 100 µm and 1000 µm, and ideally between 150 µm and 600 µm, from 10 delipidated extracts according to claim 3 of a single plant or reduced mixtures. powder and then dried to be tested on the whole human genome, by analyzing gene expression at the whole genome scale (36,000 transcribed genes and variants) of normal human epidermal keratinocytes and by hybridization on DNA microarrays, in order to list all the genes either stimulated or inhibited at maximum non-cytotoxic doses and ultimately allow the selection of plant combinations either acting on the same gene(s) for maximum effect or acting on different genes for the broadest possible activity allowing with a single semolina more powerful or more complete multifunctional effects illustrating well the "less is more" approach of the anglicism "less is more" dear to skinimalism and allowing simple extemporaneous incorporation into the aqueous phase of a cosmetic composition.