Cosmetic or dermatological compositions, in particular those targeting the action of blue light on the skin and its appendages, and related uses

A synergistic composition of chrysin, rosmarinic acid, and GQPR peptide addresses the harmful effects of blue light on skin by promoting beneficial responses and counteracting oxidative stress and inflammation, enhancing skin health and circadian rhythm synchronization.

JP7815122B2Active Publication Date: 2026-02-17SEDERMA SA
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Patent Information

Application Number
JP2022536475
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2019-12-20
Filing Date
2020-12-14
Publication Date
2026-02-17
Estimated Expiration
2040-12-14

AI Technical Summary

Technical Problem

Excessive exposure to blue light, particularly from screens, causes adverse effects on the skin such as aging, dehydration, inflammation, and disruption of circadian rhythms, while existing cosmetic solutions only address specific aspects of this issue.

Method used

A cosmetic or dermatological composition comprising chrysin, rosmarinic acid, and a peptide with the sequence GQPR, optionally modified at the N- or C-terminus, synergistically enhances beneficial effects of blue light while counteracting its harmful effects by promoting opsin 5 production, melatonin synthesis, and maintaining mitochondrial health.

Benefits of technology

The composition effectively reduces oxidative stress, inflammation, and skin degradation, enhances skin hydration and elasticity, and resynchronizes circadian rhythms, providing comprehensive protection against blue light-induced skin damage.

✦ Generated by Eureka AI based on patent content.

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Abstract

The composition comprises or consists of chrysin, rosmarinic acid, at least one peptide or derivative thereof having a sequence of 4 to 10 amino acids with the active sequence GQPR, and a physiologically acceptable medium. The derivative is an acyl group (-CO-R) at the N-terminus. 1 ), sulfonyl (-SO2-R 1 ) group or a biotinyl group, and / or at the C-terminus 1 , NH2, NHR 1 or a group of NR 1 R 2 This corresponds to the peptide modified by R 1 and R 2 are independently selected from alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxyl-containing, carbonyl-containing, phosphorylated and / or sulfur-containing, and which have 1 to 24 carbon atoms and may contain one or more heteroatoms of O, S and / or N in their backbone. The composition acts on the effects of light, more particularly on the effects of blue light, on the skin and / or its appendages, helping to counteract harmful effects and, in particularly advantageous embodiments, simultaneously increasing beneficial effects by resynchronizing the circadian cycle.
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Description

[Technical Field]

[0001] The present invention relates to cosmetic or dermatological compositions that address the effects of blue light on the skin and its appendages, and related uses. The invention is particularly aimed at the cosmetics (for humans and animals), dermatological, hygiene and personal care product industries. [Background technology]

[0002] Sunlight exposure has long been recognized as a factor increasing the risk of skin wrinkling, age spots, and sagging. Sun damage to the skin and its appendages is photochemical in nature, causing biochemical disturbances in living molecules, such as DNA, lipids, proteins, and carbohydrates, and damaging cellular organelles. Until recently, the effects of UVA (320–400 nm) and UVB (280–320 nm) were studied almost exclusively because these electromagnetic waves are very high-energy and therefore relatively photoreactive. These two types of electromagnetic radiation (UVA and B) are known to affect living organisms differently. The effects of visible light have not received particular attention because it was thought to be less dangerous due to its relatively low energy.

[0003] Visible light is the region of the solar spectrum ranging from 400 to 700 nm. Blue light is in the 400 to 500 nm range and includes violet, indigo, and blue. Blue light is similar in wavelength to UVA, but its behavior is at least partially different. Blue light is the most energetic part of the visible spectrum and is referred to as "high-energy visible light." Because of its wavelength, blue light penetrates deeper into the skin than UVA.

[0004] Visible light, at natural exposure levels, has beneficial effects on living organisms. Visible light is necessary for the production of relaxing endorphins and for the daily resynchronization of circadian rhythms (including all cyclical biological phenomena that last approximately 24 hours). This beneficial effect is particularly manifested by its action at the level of opsins (OPN). Opsins are membrane proteins that capture light energy and, upon excitation, regulate the production of melatonin, particularly the Period2 circadian protein encoded by the PER2 gene. In women, OPN5 is present in the basal epidermis. OPN5 is stimulated by blue light and plays a beneficial role in synchronizing circadian genes in the skin. The PER2 gene has a wavy production rhythm that increases in the morning and decreases in the evening. This phenomenon is significantly weakened in older adults. It is now known that OPN5 and the circadian proteins whose production is controlled by OPN5 play a crucial role in the effective functioning of the skin. Among the known effects in this sense, the following can be mentioned: stabilization of the intracellular production of oxygen radical species (ROS) and inflammatory cytokines, better hydration of the skin associated with a more effective barrier function, and reduced levels and activity of MMP1 (the main collagen-degrading enzyme), which makes it interesting that the skin has high levels of OPN5 and Period2 circadian proteins.

[0005] However, excessive exposure to the above-mentioned visible light can also have adverse effects.

[0006] In our increasingly connected world, we are exposed to artificial blue light, especially that emitted by screens, and the amount of blue light present can create a new type of pollution: digital pollution. Light from screens can cause tired eyes and frowns, leading to the formation of fine lines, which can dull the complexion and accelerate skin aging. Overexposure can accelerate signs of aging, increase skin shrinkage through fine line reduction, reduce skin hydration, cause micro-inflammation, and alter the skin barrier and underlying epidermis.

[0007] The harmful effects of blue light at the cellular level are beginning to be better understood. Blue light stimulates the production of H2O2 and oxygen-containing free radical species (ROS) by peroxisomes and mitochondria. Furthermore, it has been shown to reduce the energy produced by mitochondria. It has also been reported that blue light reduces the proliferative capacity of fibroblasts and keratinocytes. Studies on epidermal equivalents have shown that exposure to blue light caused an increase in the production of ROS, MMP-1 (a protease involved in the degradation of collagen I), and pro-inflammatory interleukins.

[0008] One particularly negative effect of blue light is its effect on melatonin, a molecule produced by the skin at night and known for its role in regulating circadian rhythms (e.g., promoting sleep). Excessive blue light interferes with melatonin production. A few hours after exposure to blue light, circulating melatonin in volunteers drops sharply.

[0009] However, melatonin does have positive effects. It exerts a direct antioxidant effect, reducing the toxicity of chemical molecules. Melatonin stimulates the mitochondrial electron transport chain and promotes the associated production of ATP, thereby reducing H2O2 production, reducing H2O2 leakage to other parts of the cell, and reducing the conversion of H2O2 to OH°. Furthermore, melatonin can promote the activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, which are involved in the detoxification of H2O2. Furthermore, melatonin and its by-products exhibit differentiation activity in keratinocytes. This is now known to favorably contribute to barrier construction, maintaining epidermal balance, and protecting the skin from the sun.

[0010] Melatonin is therefore a potential anti-aging agent, especially when it is produced in vivo and not supplied exogenously. Maintaining good skin levels of melatonin may provide local and effective protection against harmful products of ultraviolet or blue light.

[0011] Active ingredients against the harmful effects of blue light have already been proposed for cosmetic use, such as: Greentech's PHYTOBIOACTIF SOLIBERINE® (Buddleja officinalis), which protects the skin from the harmful effects of light, especially blue light. BLUESHIELD® from SOLABIA, which is based on pepper and is an antioxidant active substance that protects photoreceptors from light stress. Summary of the Invention

[0012] The object of the present invention is to provide a cosmetic or dermatological composition capable of influencing the action of light, in particular blue light.

[0013] For this purpose, the present invention provides a cosmetic or dermatological composition comprising: ·Chrysin; Rosmarinic acid; at least one peptide or derivative thereof having a sequence of 4 to 10 amino acids with the active sequence GQPR (SEQ ID NO 1); and a physiologically acceptable medium, comprising or consisting of At least one derivative is At the N-terminus, acyl (-CO-R 1 ), sulfonyl (-SO2-R 1 ) or by biotinyl groups; and / or At the C-terminus, OR 1 , NH2, NHR 1 or NR 1 R 2By; Corresponding to the modified peptides above, ·R 1 and R 2 are independently selected from alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxyl-containing, carbonyl-containing, phosphorylated and / or sulfur-containing, and which have 1 to 24 carbon atoms and may contain one or more heteroatoms in their backbone, which may be O, S and / or N, A composition is provided.

[0014] Advantageously, the inventors have shown that the composition according to the invention acts on the effects of light, more particularly on the effects of blue light, on the skin and / or its appendages, and in particular on the effects of blue light, in particular on the suppression and counteracting of the harmful effects of blue light, and in a particularly advantageous manner, at the same time on the enhancement of the beneficial effects of blue light, in particular by resynchronizing the circadian cycle.

[0015] Furthermore, and surprisingly, synergy between the three components of the composition of the present invention was demonstrated in the inhibition of inflammatory markers test described below.

[0016] More specifically, as shown by the studies described below, the compositions of the present invention enable the skin to reap the benefits of blue light, for example by promoting the synthesis of opsin 5, which, as described above, is one of the blue light photoreceptors that synchronizes circadian cycles and enhances epidermal homeostasis.

[0017] Furthermore, the composition according to the present invention, thanks to its ability to produce melatonin in skin cells, allows the skin to effectively counteract the harmful effects of blue light (oxidation, inflammation, skin degradation, dysfunction at the mitochondrial level, etc.).

[0018] This action at the cellular level may counteract the effects of high skin exposure, especially blue light exposure, which can include a dull complexion, skin fatigue, and accelerated aging.

[0019] According to the preferred features: chrysin is present in a concentration ranging from 0.2 to 20000 ppm, preferably from 2 to 2000 ppm, by weight relative to the total weight of the composition; rosmarinic acid is present in a concentration ranging from 0.1 to 10,000 ppm, preferably from 1 to 1,000 ppm, by weight relative to the total weight of the composition; and / or The peptide is present in a concentration ranging from 0.5 to 50,000 ppm by weight relative to the total weight of the composition, preferably from 5 to 5,000 ppm.

[0020] The present invention relates to the use of chrysin (5,7-dihydroxyflavone). Chrysin also encompasses analogs and derivatives of chrysin. Chrysin analogs having a flavonoid or flavone structure, preferably a substituted flavone-5,7 structure (particularly quercetin, apigenin, luteolin, or diosmetin), are included. Examples of derivatives include tectochrysin and 5-methyl ether chrysin. Chrysin or one of its analogs or derivatives may be provided in the form of a plant extract. The plant extract may be, for example, an extract of Oroxylum indicum.

[0021] Rosmarinic acid may also be provided in the form of a plant extract, in particular selected from rosemary (Rosmarinus officinalis), lemongrass, sage, basil, mint, perilla, brunell, orthosiphon, lavender, comfrey, savory, hollehound, hyssop, monarda, and many plants belonging to the families Lamiaceae (especially), Boraginaceae, and Apiaceae, preferably in the form of an extract of Rosmarinus officinalis.

[0022] Chrysin and rosmarinic acid are known for their antioxidant and anti-inflammatory properties, especially in cosmetics.

[0023] Other preferred features include: the peptide or derivative thereof comprises 4 to 8 amino acids, preferably 4 to 6 amino acids, more preferably 4 amino acids corresponding to the sequence GQPR (SEQ ID NO 1), the amino acids outside the GQPR sequence (SEQ ID NO 1), if present, being preferably selected from the 20 naturally occurring amino acids; and / or ·R 1 and / or R 2 corresponds to an alkyl chain of 3 to 24 carbon atoms; and / or The derivatized peptides contain an acyl group CO-R at the N-terminal position. 1 and / or Acyl group -CO-R 1 is selected from octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyl and lipoyl.

[0024] The peptides of the present invention may be optically pure, L- or D-isomers, or mixtures thereof. The naturally occurring L-isomer may be preferred in some cases. The peptides may optionally be in the form of a salt, particularly a hydrochloride or acetate salt.

[0025] The peptides may be natural peptides obtained by extraction and purification, or may be obtained by chemical synthesis, or may be obtained by biosynthesis via microorganisms, particularly genetically modified microorganisms, such as microalgae. The present invention also encompasses complexes of the above peptides or derivatives with other species, such as metal ions (e.g., copper, zinc, manganese, magnesium, etc.).

[0026] The peptides according to the invention may also be used in vectorized form by being bound, entrapped or adsorbed onto / to macroparticles such as capsules, spheres, liposomes, oleosomes, chylomicrons, sponges, microparticles or nanoparticles, in the form of microemulsions or nanoemulsions, or by being adsorbed onto inorganic or organic supports, for example organic polymer powders, talc, bentonite, spores or exines, or other inorganic or organic supports.

[0027] Preferably, the composition comprises the commercially available derivative peptide Pal-GQPR (SEQ ID NO 2); INCI name: Palmitoyl Tetrapeptide-7, more preferably the composition of the present invention comprises or consists of chrysin, an extract of Rosmarinus officinalis and Pal-GQPR (SEQ ID NO 2).

[0028] The results of the in vitro tests are set out below. The results demonstrate the effect of the combination of three active ingredients according to the invention by: Enhanced production of OPS5 in human keratinocytes (HK) under basal conditions or after blue light irradiation; Enhanced production of Period2 protein in basal HK; Enhancement of melatonin production in HK under basal conditions or after blue light exposure; ·Maintenance of mitochondrial membrane potential in HK after blue light irradiation; ·Maintaining or enhancing ATP synthesis capacity in HK under basal conditions or after blue light exposure; · Antioxidant activity in experimental models of lipid membranes exposed to blue light; ·Decreased production of MMP-1 in HK after blue light irradiation; A decrease in two inflammatory markers, namely PGE-2 and IL-6, in KH after blue light irradiation; and ·Maintenance of the ability to contract collagen gel in human fibroblasts (HF) after blue light irradiation.

[0029] Furthermore, in vivo studies carried out on a panel of volunteers whose facial skin quality was affected by daily exposure to blue light from screens demonstrated the effect of a cream containing a composition according to the present invention in improving the hydration, smoothness, radiance and tone of the volunteers' skin.

[0030] The present invention also proposes the use of a composition according to the invention for the non-therapeutic cosmetic treatment of the skin and / or its appendages, in particular for preventing or treating the effects of photoageing.

[0031] More specifically, the use of the composition according to the invention is proposed to prevent and / or combat the harmful effects of blue light and / or to enhance the beneficial effects of blue light. The treatment improves skin hydration, smoothness, radiance, and / or tone. The treatment is preferably topical.

[0032] By "physiologically acceptable medium" in the present invention is meant, but is not limited to, an aqueous or aqueous-alcoholic solution, a water-in-oil emulsion, an oil-in-water emulsion, a microemulsion, an aqueous gel, an anhydrous gel, a serum, a vesicle dispersion, or a powder.

[0033] "Physiologically acceptable" means that the composition can be ingested or injected into the skin without risk of toxicity, incompatibility, instability, allergic reaction, etc., and is suitable for topical or transdermal use in contact with the mucous membranes, appendages (nails, hair), scalp and skin of mammals, particularly humans. This "physiologically acceptable medium" forms what is generally called the vehicle of the composition.

[0034] Any type of physiologically acceptable medium known to those skilled in the art can be envisaged for dissolving the active agent and formulating the ingredients of the present invention, for example: aqueous solutions, alcoholic or hydroalcoholic solutions, glycolic or hydroglycolic solutions, water-in-oil emulsions, oil-in-water emulsions, microemulsions, aqueous gels, anhydrous gels, serums, vesicle dispersions, or powders.

[0035] Furthermore, the compositions according to the invention may be used in vectorized form, bound, entrapped or adsorbed onto macroparticles such as capsules, spheres, liposomes, oleosomes, chylomicrons, sponges, microparticles or nanoparticles, in the form of microemulsions or nanoemulsions, or adsorbed onto, for example, organic polymer powders, talc, bentonite, spores or exines, or other inorganic or organic supports.

[0036] The compositions according to the invention may be provided in any galenical form (examples of which are given in the following description) and may be delivered via a textile support made of natural or synthetic fibres, wool or any material suitable for use in contact with the skin, and may be applied to clothing such as day or night underwear, handkerchiefs or fabrics, so as to exert their cosmetic or dermatological effect upon contact with the skin / textile and allow continuous topical delivery.

[0037] In a particularly advantageous form, the composition according to the invention may comprise one or more additional active agents adapted to act in a reinforcing manner and / or to act in a complementary manner to one or more other activities.

[0038] Various additional active agents for this purpose are exemplified in the detailed description below.

[0039] The present invention further provides a method for improving the aesthetic appearance of the skin and its appendages, comprising topically applying to the skin an effective amount of a cosmetic or dermatological composition according to the present invention as described above.

[0040] In the present invention, "topical treatment" or "topical use" means an application intended to act where it is applied: on the skin, mucous membranes, appendages.

[0041] The compositions of the present invention can be applied topically to the area of ​​interest.

[0042] The "effective" amount depends on various factors such as the age, condition of the patient, the severity of the disorder or pathology, the mode of application, etc. An effective amount means a non-toxic amount sufficient to obtain the desired effect.

[0043] All percentages and ratios used herein are by weight of the total composition and all measurements are made at 25°C unless otherwise specified.

[0044] For example, for cosmetic treatments of the face, the European Cosmetics Directive recommends 2.72 mg / cm per person. 2 The standard application amount of cream per day is 0.5 mg / cm per person. 2 A standard application amount of body lotion per day has been set.

[0045] According to another particular feature, the cosmetic treatment method according to the present invention may be combined with one or more other treatment methods targeting the skin, such as, for example, light therapy, heat therapy, vibration therapy, electrotherapy, microneedle patch or aromatherapy treatment.

[0046] According to the present invention, there is proposed a multi-compartment device or kit for applying the methods described above, which may contain, for example but not limited to, an active ingredient according to the invention in a first compartment and another active ingredient and / or excipient in a second compartment, in which case the compositions contained in said first and second compartments are treated in particular as a combined composition for simultaneous, separate or stepwise use in one of the treatment methods described above.

[0047] The compositions according to the invention are also suitable for therapeutic treatment of the skin in appropriate doses. DETAILED DESCRIPTION OF THE INVENTION

[0048] The present invention will be better understood with reference to the following description of the embodiments and in vitro and in vivo tests.

[0049] A / Example of the preparation of a preferred composition according to the invention, forming a concentrated component which is a combination of three active ingredients according to the invention, intended to produce a galenical preparation (see paragraph D / )

[0050] The components include: Chrysin: Origin: Synthetic, at least 94% pure Final concentration of chrysin in the composition: 200 ppm Rosmarinic acid: Source: Rosmarinus officinalis (rosemary) leaf extract with at least 6% rosmarinic acid Final concentration of rosmarinic acid in the composition: 60 ppm Palmitoyl-GQPR-OH (SEQ ID NO:2), at least 99% pure Origin: Synthetic Final concentration of palmitoyl-GQPR-OH (SEQ ID NO: 2) in the composition: 750 ppm · Excipients: glycolic acids.

[0051] B / Synergy test

[0052] protocol HKs are cultured in medium. After rinsing with PBS, the cells are returned to this same buffer and irradiated with 30.2 J / cm 2 The exposure system is 30cm 2 The photon beam reaches the cells perpendicularly. The temperature is controlled and all cells are placed in the same enclosure (37°C / 5% CO2). The center of the emission spectrum is 420 nm. The cells are then contacted with each of the compounds of the present invention (prepared separately) or with the composition of the present invention for 24 hours. The medium is then collected and assayed for IL-6 concentration by ELISA. The cell layer is assayed to show a decrease in cell number.

[0053] result Changes in IL-6 production in HK after blue light irradiation; comparison of the effect of the composition of the present invention with the sum of the effects of multiple compounds of the composition prepared separately.

[0054] [Table 1]

[0055] The above results demonstrate a synergistic effect in countering the effects of blue light when the three compounds are combined in the test: the improvement in inhibition of IL-6 production is 46.2% (p<0.01) for the composition according to the present invention compared to the sum of the three compounds tested separately.

[0056] C / In vitro efficacy test of the composition according to the invention

[0057] Tests were performed on the equivalent of a preferred composition of the present invention: 750 ppm palmitoyl-GQPR-OH (SEQ ID NO 2), 200 ppm chrysin, and 1000 ppm rosemary extract (corresponding to 60 ppm rosmarinic acid in the composition). This equivalent was used at 0.5, 1, or 2% in tests on human fibroblasts (HF). These concentrations are within the range recommended for applying cosmetic active ingredients to the skin.

[0058] [Table 2]

[0059] In vitro tests on human keratinocytes (HK) were carried out on the equivalent of the composition of the present invention: 750 ppm palmitoyl-GQPR, 80 ppm chrysin, and 1000 ppm rosemary extract (corresponding to 60 ppm rosmarinic acid in the composition). This equivalent was used at 0.5, 1, or 2%. These concentrations are within the range of concentrations recommended for applying active ingredients of cosmetic compositions to the skin.

[0060] [Table 3]

[0061] Chrysin and Pal-GQPR were presolubilized in DMSO (1000 times the final test concentration) before being introduced into the aqueous test medium. Rosemary leaf extract dissolves directly in aqueous media.

[0062] 1 / Reduction of intracellular radical species

[0063] protocol Normal human fibroblasts (HNF) are grown in culture until confluent, and then the cells are contacted with the composition of the present invention for 24 hours, followed by the fluorescent probe that marks the intracellular production of ROS.

[0064] After 30 minutes of uptake and rinsing, the cells are again treated with the composition of the present invention, followed by either no treatment or treatment with an agent intended to generate ROS (oxidative stress). The amount of ROS in the cells is evaluated by fluorescence measurement (excitation: 490 nm / fluorescence: 520 nm). The cell number is evaluated using the Hoechst 33258 method (DNA staining), and the obtained data are discussed.

[0065] result Changes in ROS production in NHF with or without oxidative stress (n=3)

[0066] [Table 4]

[0067] The above results show that the composition of the present invention reduces the intracellular content of ROS both under basal conditions and under conditions of oxidative stress. In both cases, the reduction in intracellular ROS content is significant and pronounced, making the composition of the present invention interesting for combating the generation of intracellular ROS, which is known to be involved in skin aging.

[0068] 2 / Production of opsin-5 (OPN5)

[0069] 2.1 / ​​qRT-PCR assay (quantitative real-time reverse transcription polymerase chain reaction)

[0070] protocol Subconfluent HKs were synchronized (all in the same phase of the cell cycle) by exposing them to DMEM medium containing 50% serum for 2 hours. After rinsing with PBS, the cells were returned to this same buffer and exposed to 30.2 J / cm 2The cells are exposed to a non-cytotoxic dose of blue light of 1000 kJ / ml. The exposure system is the same as that described in B) above. At the end of the exposure, the irradiated or non-irradiated cells are contacted with the composition of the present invention for 3 hours. Total RNA is then extracted, and production of the gene encoding OPN5 is assessed by qRT-PCR molecular biology.

[0071] result Changes in OPN5 production in HK after 3 hours of contact with the composition of the present invention (n=3)

[0072] [Table 5]

[0073] The above results clearly demonstrate that blue light can favorably regulate the production of the gene encoding the OPN5 protein in HK in vitro (+182% over the control).The above results also demonstrate that the composition of the present invention strongly promotes the production of the OPN5 gene in the presence or absence of blue light compared to the control.

[0074] 2.2 / Immunocytochemical assay

[0075] protocol The same culture and irradiation protocol as described above (2.1 / ) (or none in the case of non-irradiation) is carried out in HK. The cells, whether irradiated or not, are contacted with the composition of the present invention for 12 hours (or nothing as a control). The cell layer is then labeled with an anti-OPN5 protein antibody. Photographs are taken, and the resulting images are analyzed and compared. Cells are counted by nuclear counter-labeling using the Hoescht 33258 method (DNA staining), and the results are discussed.

[0076] result Changes in OPN5 production in HK after 12 hours of contact with the composition according to the invention (4 cultures per case, 16 photographs per culture).

[0077] [Table 6]

[0078] The above results confirm the following data obtained in molecular biology: Exposure to blue light increases the production of OPN5 in controls; and Contacting the cells with the composition according to the invention, whether irradiated or not, increases this production compared to the control.

[0079] 3 / Production of Period2, a protein with a circadian rhythm

[0080] protocol As described above in 2.1 / . At the end of the exposure (only in the case of controls), the non-irradiated cells are contacted with the composition of the invention (or nothing in the case of controls). Total RNA is extracted in 3 hours and the production of the gene encoding PER2 is evaluated by qRT-PCR.

[0081] result Changes in PER2 production in HK after 3 hours of contact with the composition of the present invention (n=3)

[0082] [Table 7]

[0083] The above results indicate that blue light promotes the production of PER2 in cultured cells. The above results confirm that the cultured cells have an altered chromophore. Advantageously, PER2 production is also promoted by contacting cells with the composition of the present invention, but does not require exposure to blue light.

[0084] 4. Melatonin production

[0085] protocol The procedure is the same as described in 2.1 / above. At the end of the exposure, irradiated or non-irradiated cells are contacted with the composition of the present invention (or no contact in the control). All cultures are stopped after 12 hours. The medium is removed and the amount of melatonin is assayed by ELISA. The results are normalized using the total amount of RNA detected in the cell layer of each sample.

[0086] result Changes in melatonin production in HK after 12 hours of contact with the composition of the present invention (n=3)

[0087] [Table 8]

[0088] The results show that blue light reduces melatonin production by 38% (p<0.02) in the selected illumination system. These results are likely related to the direct or indirect intracellular production of ROS by blue light, which "consumes" this natural antioxidant. In contrast, the composition of the present invention promotes the production of this natural anti-aging molecule, both with and without illumination. The promotion is dose-dependent and significant in both cases. Thus, the composition of the present invention exhibits a dual effect: it effectively combats ROS and also promotes the production of intracellular antioxidants.

[0089] 5. Mitochondrial membrane potential

[0090] protocol HKs are grown in culture medium until confluent. After placing in the appropriate buffer, the cells are exposed to blue light as described above (B / ). The cells are then placed in contact with the composition of the present invention for 25 hours. The mitochondrial membrane potential in live cells is then assessed by measuring the monomeric cytoplasmic (green) and aggregated (red-yellow) mitochondrial morphology of JC-10 dye at two different wavelengths. A low monomer / aggregate ratio indicates good mitochondrial health. The number of cells is counted and the results are discussed by nuclear staining using the Hoescht 33258 method (DNA stain).

[0091] result Changes in mitochondrial membrane potential in HK: Effect of the composition of the present invention (25 hours of contact)

[0092] [Table 9]

[0093] Mitochondrial membrane potential is the gradient of electrical charge resulting from mitochondrial function. Disturbances in mitochondrial membrane potential indicate stress and can lead to injury and disease. The results show that blue light significantly alters mitochondrial membrane potential in HK. Reflecting the disturbances in mitochondria, the proportion of monomeric to polymeric forms increased sharply, showing a ratio increase of 33% (p<0.01). After this irradiation, the base mitochondrial membrane potential can be maintained by using the composition of the present invention.

[0094] 6 / Mitochondrial ATP synthesis

[0095] protocol The same protocol as in 5 / is followed. After 25 hours of contact with the composition of the present invention (or no contact in the control case), intracellular ATP is extracted and assayed by bioluminescence. The signal obtained is proportional to the amount of ATP in the cells. The number of cells is counted by staining the nuclei using the Hoescht method (DNA stain) and the results are discussed.

[0096] result Changes in ATP pool in HK; effect of the composition according to the invention (25 hours of contact).

[0097] [Table 10]

[0098] ATP is an energetic building block of living organisms. ATP enables metabolism to function and proteins to be manufactured. Energy production is reduced in aged or stress-damaged mitochondria. The results show that ATP production decreased after exposing cells to blue light. This is consistent with known findings and observations regarding changes in mitochondrial potential. The composition of the present invention promotes energy production in mitochondria, both with and without irradiation, compared to control cases. Without irradiation, the promotion reached +53% (p<0.01) of the control. With irradiation, the promotion reached +87% (p<0.01) compared to the irradiated control.

[0099] 7. Peroxidation of lipid membranes

[0100] principle Lipid membranes surround cells and mitochondria, where they actively maintain the mitochondrial membrane potential. Membrane peroxidation weakens the membrane and autocatalytically generates oxygen free radicals, which amplify the damage.

[0101] protocol Lipid membrane models of liposomes are exposed to blue light (according to the conditions described above for cells in B / ). The composition according to the invention is added after irradiation or not (control case). Lipid peroxidation is measured by absorbance at 233 nm (absorption wavelength of conjugated dienes).

[0102] result Measurement of lipid peroxidation in liposomes (a model of lipid membranes); effect of the composition of the present invention.

[0103] [Table 11]

[0104] The compositions of the present invention strongly and dose-dependently reduce lipid peroxidation, thereby protecting lipid membranes from oxidative damage caused by blue light.

[0105] 8 / MMP-1 gene production

[0106] protocol HKs are grown in culture medium until confluent. After placing in the appropriate buffer, the cells are exposed to blue light as described above (B / ), and then contacted with the composition of the present invention for 6 hours. Total RNA is extracted and quantified and analyzed by transcriptome analysis of mRNA chips. Ten copies of the MMP1 gene detection probe are present on the mRNA chip, and two biological replicates are quantified. Thus, for each MMP1 gene detection probe, n = 20 per condition.

[0107] result Changes in the production of the MMP-1 gene in HK, effect of the composition according to the invention (6 hours of contact).

[0108] [Table 12]

[0109] The above results clearly show that in the irradiation system studied, blue light causes a 205% (p<0.01) increase in the production of the MMP1 gene, which encodes the eponymous protein, whereas the composition according to the invention, at 2%, slows down the production of this molecule, which is strongly involved in the phenomenon of extracellular matrix degradation, after irradiation of cells with blue light.

[0110] 9 / Production of inflammatory mediators

[0111] protocol HKs are cultured in a medium. After placing in an appropriate buffer, the cells are exposed to blue light as described above (B / ). The cells are then contacted with the composition of the present invention for 24 hours. The medium is then collected and assayed for IL-6 and PGE2 concentrations by ELISA. Assay of the cell layer reveals a decrease in cell number.

[0112] result Changes in IL-6 protein production in HK; effect of the composition of the present invention (24-hour contact).

[0113] [Table 13]

[0114] Changes in the production of the pro-inflammatory lipid PGE-2 in HK; effect of the composition of the present invention (24 hours of contact).

[0115] [Table 14]

[0116] The above results (Tables 11 and 12) clearly show that blue light increases the synthesis of cytokines IL-6 and PGE2 by 147% and 108%, respectively (both p<0.01). Meanwhile, the composition of the present invention inhibits the synthesis of these pro-inflammatory molecules after irradiating cells with blue light. In the case of PGE2, the inhibition is significant and dose-dependent.

[0117] 10. Cellular elasticity after stress

[0118] protocol NHFs are cultured in culture medium until confluent. The NHFs are then irradiated with blue light (as in B / ) and then contacted with the composition of the present invention for 24 hours. The cells are then separated and incorporated into a collagen gel to form an epidermal equivalent. The contraction of the gel by the cells is observed. The area of ​​the gel is measured, and the delta of the areas versus T0 is calculated for each condition.

[0119] result Changes in collagen gel contraction due to HF; effect of the composition according to the invention (24 hours of contact).

[0120] [Table 15]

[0121] The results above show that blue light reduces the ability of fibroblasts to contract collagen gel (-36%). The results also show that the composition of the present invention maintains the contractile force of fibroblasts even when irradiated with blue light, demonstrating the ability of skin to maintain its elasticity when subjected to the above stresses.

[0122] D / Galenic preparations / Preparation of the compositions according to the invention

[0123] The compositions according to the invention may comprise additional cosmetic active ingredients, which may be introduced in the form of ingredients or as supports and / or active complements during the preparation of the final cosmetic composition for the consumer, and which may be applied to the face, body, neck, scalp, hair, eyelashes, body hair, nails, or lips in any form or medium known in the art, in particular in the form of a solution, dispersion, emulsion, paste, or powder, individually, as a premix, or delivered individually or as a premix.

[0124] In cosmetics, they can be used in particular in the fields of skin care for the face, body, hair and body hair, and in the field of make-up care.

[0125] The additional active agents may be of any category depending on the function of the active agent, the location of application (body, face, neck, chest, hands, hair, eyelashes, eyebrows, body hair, nails, lips, etc.), the desired end effect, and the target consumer, and the categories may be, for example, antioxidant, firming, moisturizing, nourishing, protecting, smoothing, remodeling, volumizing (lipofilling), complexion brightening, anti-dark spot, anti-dark circles, anti-glycation, anti-aging, anti-wrinkle, slimming, soothing, muscle relaxing, anti-redness, anti-stretch mark, sunscreen, etc.

[0126] The CTFA (International Cosmetic Ingredient Dictionary & Handbook (19th Ed. 2019), published by the Personal Care Products Council, formerly the Cosmetic, Toiletry, and Fragrance Association, Inc., Washington, DC) describes a wide variety of non-limiting cosmetic and pharmaceutical ingredients commonly used in the skin care industry that are suitable for use as additional ingredients in the compositions of the present invention.

[0127] Examples include at least one compound selected from the following: vitamin B3 compounds, such as niacinamide or tocopherol; retinoid compounds, such as retinol, hexamidine, α-lipoic acid, resveratrol or DHEA; hyaluronic acid; peptides, in particular Pal-KTTKS (SEQ ID NO 3), N-acetyl-Tyr-Arg-O-hexadecyl ester, Pal-VGVAPG (SEQ ID NO 4), Pal-KTFK (SEQ ID NO 5), Pal-GHK, Pal-KMO2K, and / or Pal-K(P)HG (with proline grafted to lysine), which are widely used active ingredients in topical cosmetic or dermopharmaceutical compositions.

[0128] For further additional skin care actives that may be particularly useful, see Sederma's trade literature and website at www.sederma.com.

[0129] In general, the following commercially available activators may also be mentioned as examples: For example, betaine, glycerol, ActimoistBio2™ (Active organics), AquaCacteen™ (Mibelle AG Cosmetics), Aquaphyline™ (Silab), AquaregulK™ (Solabia), Carciline™ (Greentech), Codiavelane™ (Biotech Marine), Dermaflux™ (Arch Chemicals, Inc.), Hydra' Flow™ (Sochibo), Hydromoist L™ (Symrise), RenovHyal™ (Soliance), Seamoss™ (Biotech Marine), Argireline™ (trade name of acetyl hexapeptide-3 by Lipotec), extract of Acmella oleracea known under the trade name spilanthol or Gatuline Expression™, extract of Boswellia serrata known under the trade name Boswellin™, Deepaline PVB™ (Seppic), Syn-AKE™ (Pentapharm), Ameliox™, Bioxilift™ (Silab), PhytoCellTec™ Argan (Mibelle), Papilactyl DD™ (Silab), Preventhelia™ (Lipotec), and the following Sederma products: Subliskin™, Venuceane™, Moist 24™, Vegesome Moist 24™, Essenskin™, Juvinity™, Revidrat™, Resistem™, Chronodyn™, Kombuchka™, Chromocare™, Calmosensine™, Glycokin factor S. S™, Biobustyl™, Idealift™, Ceramide 2™, Ceramide A2™, Ceramide HO3 HO3™, Legance™, Intenslim™, Prodizia™, Beautifeye™, NG-Shea Butter Unsaponifiables (Natural Grade), Zingerslim™, Meiritage™, Senestem™, Sebuless™, Majestem™, Apiscalp™, Rubistem™, Citystem™, Neonyca™, NG-Shea Butter Unsaponifiables (Natural Grade) Karite™, Majestem™, Hydroonesis™, Poretect™, Crystalide™, Amberstem™, Feminage™, or mixtures thereof.

[0130] Among the plant extracts that can be combined with the peptides of the present invention, there are extracts of ivy, in particular English ivy (Hedera Helix), extracts of Bupleurum chinensis, extracts of Bupleurum falcatum, extracts of arnica (Arnica Montana L), extracts of rosemary (Rosmarinus officinalis N), extracts of marigold (Calendula officinalis), extracts of sage (Salvia officinalis L), extracts of ginseng (Panax ginseng), extracts of ginkgo biloba, extracts of St. John's wort (Hyperycum perforatum), extracts of Ruscus aculeatus L, extracts of European meadowsweet (Filipendula ulmaria L), extracts of big-flowered Java tea (Orthosiphon stamincus Benth), extracts of algae (Fucus Vesiculosus extract, birch (Betula alba) extract, green tea extract, cola nut (Cola Nipida) extract, horse chestnut extract, bamboo extract, Centella asiatica extract, heather extract, fucus extract, willow extract, mouse-ear extract, escin extract, canzhu extract, chrysanthellum indicum extract, Armeniacea plant extract, Atractylodis platycodon extracts of plants of the genus Platicodon, extracts of plants of the genus Sinnomenum, extracts of plants of the genus Pharbitidis, extracts of plants of the genus Flemingia, extracts of Coleus, where Coleus is, for example, C. forskohlii, C. blumei, C. esquirolii, C. scutellarioides,scutellaroides, C. xanthantu and C. barbatus, an extract of C. barbatus being, for example, an extract of the root of Coleus barbatus, an extract of Ballote, an extract of Guioa, an extract of Davallia, an extract of Terminalia, an extract of Barringtonia, an extract of Trema, an extract of Antirobia, Cecropia, argania, Dioscoreae, where Dioscoreae is, for example, Dioscorea opposita or Mexican, Ammibisnaga extracts of vegetables from the Ericaceae family, in particular bilberry (Vaccinium angustifollium) extracts or bearberry (Arctostaphylos uva ursi) extracts; vegetable extracts of aloe vera; vegetable extracts of plants containing sterols (e.g., phytosterols); vegetable extracts of Manjistha (extracted from plants of the genus Rubia, in particular Rubia cordifolia); and vegetable extracts of Guggal (extracted from plants of the genus Commiphora, in particular Guggul). Mukul), kola extract, chamomile, red clover extract, kava (Piper methysticum) extract (Kava Kava®, Sederma), Bacopa monieri extract (Bacocalmine®, Sederma), sea whip extract, Glycyrrhizaglabra extract, Mulberry extract, Melaleuca (Tea Tree) extract, Larrea divaricata extract, Rabdosia rubescens extract, Euglena gracilis extract, Fibraurea recisa Hirudinea extract, Chaparral Sorghum extract, Sunflower extract, Enantia chlorantha extract, Mitracarpe of Spermacocea genus extract, Buchu barosma extract, Henna L (Lawsonia inermis L), Adiantum capillus-veneris L L) extract, Celandine (Chelidonium majus) extract, Luffa (Luffa cylindrica) extract, Japanese Mandarin (Citrus reticulata Blanco var. unshiu) extract, Tea plant (Camelia sinensis) extract, Imperata cylindrica extract, Horn poppy (Glaucium flavum) extract, Cypress (Cupressus sempervirens) extract, Solomon's seal (Polygonatum multiflorum) extract, Lovely hemsleya extract, Elderberry (Sambucus nigra) extract, Lima bean (Phaseolus lunatus) extract, Centaurium japonica extract, Macrocystis Pyrifera (Turnera Diffusa) Extract, Anemarrhena asphodeloides (Anemarrhena asphodeloides) Extract, Portulaca pilosa (Portulaca pilosa) Extract, Hops (Humuluslupulus extract, Arabica coffee (Coffea Arabica) extract, Yerba mate (Ilex Paraguariensis) extract, Globularia Cordifolia extract, Silk tree (Albizzia julibrissin) extract, Oxydendron arboretum extract, Zingimber Zerumbet Smith extract, Astragalus membranaceus extract, Atractylodes macrocephalae extract, Plantago lanceolata extract, Mirabilis jalapa extract, Celery (Apium graveolens) extract, Horehound (Marrubium vulgare) extract, Buddleja davidii extract Franch extract, Engelhardia chrysolepis extract, Syringa vulgaris extract or orchid extract may be mentioned in particular.

[0131] The compositions of the present invention may include one or more additional peptides, including but not limited to dipeptides, tripeptides, tetrapeptides, pentapeptides, and hexapeptides and derivatives thereof. According to certain embodiments, the concentration of the additional peptide in the composition is greater than or equal to 1×10 -7 % to 20% by weight, and 1×10 -6 The range of 1×10 wt.% to 10 wt.% is preferred. -5The preferred range is 10% to 5% by weight. As used herein, the term "peptide" refers to peptides containing 10 or fewer amino acids, their derivatives, isotopes, and complexes with other species, such as metal ions (copper, zinc, manganese, magnesium, etc.). The term "peptide" refers to both natural and synthetic peptides. The term "peptide" also refers to compositions containing peptides found in nature and / or commercially available.

[0132] Dipeptides suitable for use herein include, but are not limited to, carnosine (βAH), YR, VW, NF, DF, KT, KC, CK, KP, KK, TT, PA, PM, or PP.

[0133] Tripeptides suitable for use herein include RKR, HGG, GKH, GHK, GGH, GHG, KGH, KHG, KFK, KAvaK, KβAK, KAbuK, KAcaK, KPK, KMOK, KMO2K (MO2 is sulfoxide methionine dioxide), KVK, PPL, PPR, SPR, QPA, LPA, SPA, K(Ac)HG, K(Ac)GH, where K(Ac) is an amino acid having an acetylated side chain as disclosed in WO2017 / 216177. K(P)HG, K(P)GH, where K(P) is a lysine with a side chain grafted with proline; K(Pyr)HG, K(Pyr)GH, where K(Pyr) is a lysine with a side chain grafted with pyroglutamic acid; K(Hyp)HG, or K(Hyp)GH, where K(Hyp) is a lysine with a side chain grafted with hydroxyproline as disclosed in WO2016 / 097965.

[0134] Tetrapeptides suitable for use as additional peptides herein include, but are not limited to, RSRK (SEQ ID NO:6), KTFK (SEQ ID NO:7), KTAK (SEQ ID NO:8), KAYK (SEQ ID NO:9) or KFYK (SEQ ID NO:10).

[0135] A suitable, non-limiting example of a pentapeptide is KTTKS (SEQ ID NO:11), and suitable examples of a hexapeptide are GKTTKS (SEQ ID NO:12) and VGVAPG (SEQ ID NO:13).

[0136] Other peptides suitable for use in accordance with the present invention may be selected from the following, but this list is not limiting: lipophilic derivatives of peptides, preferably palmitoyl (Pal) or myristoyl (Myr) derivatives, and metal complexes of the above (e.g., copper complexes of the tripeptides HGG or GHK). Preferred dipeptides include, for example, N-palmitoyl-β-Ala-His, N-acetyl-Tyr-Arg-hexadecyl ester (Calmosensine™, Idealift™, Sederma), Pal-RT or Pal-KT (Sederma). Preferred tripeptide derivatives include, for example, Pal-GKH and Pal-GHK (Sederma), the copper derivative of HGG (Lamin™, Sigma), lipospondin (N-elidoyl-KFK) and its conservatively substituted analogs, N-acetyl-RKR-NH2 (peptide CK+), N-Biot-GHK (Sederma), Pal-KAvaK, Pal-KβAlaK, Pal-KAbuK, Pal-KAcaK, or Pal-KMO2K (Matrixyl® Synthe' 6®, Sederma), Pal-KVK (Syn-Coll™, DSM), and derivatives thereof.

[0137] In this specification, the general formula described in the WO2015181688 application is X-Pro * -Pro * An example of an anti-aging tripeptide is -Xaa-Y, where Xaa is selected from Leu, Arg, Lys, Ala, Ser, and Asp. At the N-terminus, X is H, -CO-R 1 and SO2-R 1At the C-terminus, Y is selected from OH, OR 1 , NH2, NHR 1 or NR 1 R 2 Selected from: R 1 and R 2 are independently selected from alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, contain hydroxyl groups, contain carbonyl groups, may be phosphorylated and / or sulfurized. The backbone of the above groups may contain heteroatoms, in particular O, S and / or N. Pro * corresponds to proline, its analogs or derivatives; for example, the general formula X-Pro * -Pro * -Xaa-Y comprises Myr-PPL-OH and Myr-PPR-OH.

[0138] In the present specification, the general formula disclosed in WO2014 / 080376 is X-(Xaa1)n-Pro *Examples include propigmenting and / or pro-mec dipeptides and tripeptides of -Xaa2-Y, where n=0, 1, or 2. Xaa1 is a hydrophobic amino acid selected from Ala, Val, Met, Leu, Iso, Phe, and Pro, and analogs and derivatives thereof; or a polar amino acid selected from Ser, Thr, Tyr, Asp, and Glu, and analogs and derivatives thereof; when n=2, the two amino acids Xaa1 are the same or different; and Xaa2 is a hydrophobic amino acid selected from Ala, Val, Met, Leu, Iso, and Phe, and analogs and derivatives thereof, or a basic amino acid selected from Arg, Lys, and His, and analogs and derivatives thereof. At the N-terminus, X is selected from H, -CO-R1, and SO2-R1; at the C-terminus, Y is selected from OH, OR1, NH2, NHR1, or NR1R2; R1 and R2 are independently selected from alkyl, aryl, aralkyl, alkylaryl, alkoxy, and aryloxy groups, which may be linear, branched, cyclic, or polycyclic, saturated or unsaturated, may contain hydroxyl groups, may contain carbonyl groups, may be phosphorylated, and / or sulfurized. The backbone of the above groups may or may not contain heteroatoms, which are O, S, and / or N. Pro * corresponds to proline, its analogues or derivatives; for example, the general formula X-(Xaa1)n-Pro * -Xaa2-Y comprises the following peptides: Pal-SPR-OH, Pal-PPR-OH, Pal-QPA-OH, Pal-LPAOH, Myr-SPA-OH, Pal-PM-OH, Pal-PA-OH and Pal-PP-OH.

[0139] Tetrapeptide derivatives suitable for use as additional peptides according to the present invention include, but are not limited to, Pal-KTFK (SEQ ID NO: 5), Ela-KTFK (SEQ ID NO: 14), Ela-KTAK (SEQ ID NO: 15), Ela-KAYK (SEQ ID NO: 16), or Ela-KFYK (SEQ ID NO: 17). Pentapeptide derivatives suitable for use as additional peptides herein include, but are not limited to, Pal-KTTKS (SEQ ID NO: 3) (available from Sederma as Matrixyl®), Pal-YGGFXaa (SEQ ID NO: 18) where Xaa is Leu or Pro, or mixtures thereof.

[0140] Examples of hexapeptide derivatives suitable for use herein include, but are not limited to, Pal-VGVAPG (SEQ ID NO:4), Pal-GKTTKS (SEQ ID NO:19), Pal-HLDIIXaa where Xaa is Trp, Phe, Tyr, Tic, 7-hydroxy-Tic, or Tpi (SEQ ID NO:20), and derivatives thereof. Also exemplified is a mixture of Pal-GHK and Pal-GQPR (SEQ ID NO:2) (Matrixyl® 3000, Sederma).

[0141] The following commercially available peptides may also be mentioned, along with additional active ingredients: Vialox™ (INCI name = Pentapeptide-3 (synthetic peptide comprising alanine, arginine, isoleucine, glycine, and proline)), Syn-Aake™ (β-Ala-Pro-Dab-NH-Bzl) or Syn-Coll™ (Pal-Lys-Val-Lys-OH), sold by Pentapharm; Argireline™ (Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 (INCI name: Acetyl Hexapeptide-3) (SEQ ID NO: 21), Leuphasyl™ (Tyr-D-Ala-Gly-Phe-Leu) (SEQ ID NO: 22), Aldenine™ (Gly-His-Lys), Trylagen™ (INCI names: Pseudoalteromonas Ferment Extract, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-10), all sold by Lipotec Citrulline (reaction product of citrulline and tripeptide-10 (a synthetic peptide composed of aspartic acid, isoleucine, and lysine)), Tripeptide-1), Eyeseryl™ (Ac-β-Ala-His-Ser-His) (SEQ ID NO: 23), Serilesine™ (Ser-Ile-Lys-Val-Ala-Val) (SEQ ID NO 24) or Decorinyl™ (INCI name: Tripeptide-10 Citrulline = reaction product of citrulline and tripeptide-10 (a synthetic peptide composed of aspartic acid, isoleucine, and lysine)); Collaxyl™ (Gly-Pro-Gln-Gly-Pro-Gln (SEQ ID NO 25)) or Quintescine™ (Cys-Gly), available from Vincience; Cytokinol™ LS (casein hydrolysate), sold by Les Laboratoires Serobiologiques / Cognis; Kollaren™ (Gly-His-Lys), IP2000™ (Pal-Val-Tyr-Val) or Meliprene™ (INCI name = Monofluoroheptapeptide-1: reaction product of acetic acid with a synthetic peptide comprising arginine, glycine, glutamic acid, histidine, norleucine, p-fluorophenylalanine and tryptophan), sold by the European Biological Institute; Neutrazen™ (Pal-His-D-Phe-Arg-NH2), available from Introvations; or BONT-L-Peptide™ (INCI name: Palmitoyl Hexapeptide-19, reaction product of palmitic acid with hexapeptide-19 (a synthetic peptide composed of asparagine, aspartic acid, lysine, and methionine)), Timp-Peptide™ (INCI name: Acetyl Hexapeptide-20, reaction product obtained by acetylation of hexapeptide-20 (a synthetic peptide composed of alanine, glycine, lysine, valine, and proline)), or ECM Moduline™ (INCI name: Palmitoyl Tripeptide-28, reaction product of palmitic acid with tripeptide-28 (a synthetic peptide composed of arginine, lysine, and phenylalanine)), all sold by Infinitec Activos.

[0142] It may also be envisaged to combine the plant cells according to the invention with one or more cyclic peptides, in particular those extracted from linseed oil, as described in the Applicant's patent application FR1850845.

[0143] Various compositions / formulations according to the present invention are described below, along with some examples of additional active ingredients.

[0144] The compositions according to the invention forming the active ingredient concentrates according to the invention are as described above in point A / .

[0145] This component is generally present in the range of 0.1% to 20%, preferably 1 to 10%, more preferably 2 to 5%.

[0146] 1) Day Cream [Table 16]

[0147] 2) Night cream [Table 17]

[0148] Examples of additional ingredients: Soothing ingredients for sensitive skin, including: PACIFEEL™, sold by Sederma, comprises an extract of Mirabilis Jalapa. Hydrating ingredients such as: AQUALANCE™, sold by Sederma, is an osmotic stabilizer containing homarine and erythritol with hydrating activity. REVIDRAT™, marketed by Sederma, specifically improves epidermal cohesion and hydration. Brightening ingredients include: EVERMAT™, sold by Sederma, contains a combination of protoberberine-rich extract of Enantia chlorantha and oleic acid; reduces pore size and shine; and improves the texture of acne-prone skin. Moisturizing / smoothing ingredients such as: OPTIM HYAL™, sold by Sederma, contains oligosaccharides of acetylated glucuronic acid with a structure similar to fragments of hyaluronic acid. Sebum-regulating ingredients such as: SEBULESS™: Marketed by Sederma, it contains an extract of lilac (Syringa vulgaris) obtained through in vitro cell culture, which acts as a clarifying sebo-regulator, reduces shine, refreshes the complexion, and reduces the appearance of imperfections. PORETECT™: Marketed by Sederma, this is a combination of flaxseed extract and celery extract titrated with cylolinopeptides and senkyunolides, which gives skin firmness, tone and density, strengthening the structure that holds pores together, which can break down with age. Ingredients that affect the elastic properties of the skin / skin barrier, such as: IDEALIFT™: Marketed by Sederma, it contains the lipodipeptide N-acetyl-tyrosyl-arginyl-O-hexadecyl ester, which combats facial sagging and improves resistance to gravity by specifically stimulating elastin. DERMAXYL™: Sold by Sederma, this product combines the stratum corneum binding agent ceramide 2 with palmitoylated matrikine Pal-Val-Gly-Val-Ala-Pro-Gly to smooth wrinkles and repair the skin barrier. Anti-fatigue ingredients such as: PRODIZIA™, marketed by Sederma and containing extract of the silk tree (Albizia julibrissin), promotes the visible reduction of signs of fatigue: dark circles, bags under the eyes, dull complexion, and drawn lines by repairing and protecting the skin from the damage caused by glycation. Anti-pollution ingredients such as: CITYSTEM™, marketed by Sederma and based on plant cells obtained in vitro from the horehound plant (Marrubium vulgare) with a high concentration of Forsythoside B; used to combat pollution: the skin becomes softer, smoother, the skin texture is improved, acne is less visible, and the skin becomes more radiant and cleaner.

[0149] E / In vivo testing general principle The effect of the composition of the present invention is evaluated on 27 volunteers.Because it is not possible for volunteers to be exposed to blue light for hours, panelists with special characteristics are selected.In all these tests, volunteers are forced to face screens to a considerable extent every day, so that they feel some degree of fatigue, and this fatigue is reflected on their face.In particular, volunteers may show dull complexion, skin troubles, and / or "fatigue / wrinkles", and their facial skin may lose moisture, and their face may lose tone and radiance.

[0150] The benefits of the compositions of the present invention were tested in terms of: hydration, smoothing, radiance, skin tone and skin fatigue.

[0151] The test was carried out on the face over an 8-week period (measurements were taken at week T0 and week T8).

[0152] In this test, volunteers applied a day cream in the morning and a night cream in the evening (the formulation of Galen's Part D above) to one side of their face. Placebo day and night creams (the same formulation without the active ingredient) were applied to the other side of their face in the same way. The volunteers did not know which cream corresponded to the present invention.

[0153] Statistical tests were performed by Student's t-test or, where appropriate, the non-parametric Wilcoxon test. Two-tailed tests were performed on paired series.

[0154] 1 / Hydration

[0155] method The test uses an innovative device, Epsilon™, which has the special feature of providing an image of hydration rather than a value. It is based on Skinchip™ technology. It is equipped with a sensor with 76,800 pixels measuring to a depth of 50 μm. Each pixel gives a value of the dielectric constant of the skin, ε. This parameter varies between 0 and 85 (air = 1, water = 80). The measurement results in an image, which makes it possible to visually evaluate the effect of the tested substance on the skin's topography, and also on the homogeneity or softness of the skin, as hydration improves the above parameters.

[0156] result Changes in skin hydration; effect of the cream according to the present invention (N=27)

[0157] [Table 18]

[0158] After two months of application of the cream according to the invention, the skin is more hydrated compared to the placebo (p<0.01), with no significant benefit for the placebo.

[0159] 2 / Skin smoothing

[0160] method For the evaluation of this item, Epsilon™ was used, which also provides information on the smoothing aspect. The image negative obtained for hydration provides information on this item. Fewer pixels in the image indicate a smoothing effect.

[0161] result Changes in skin relief (more or less smooth appearance); effect of a cream according to the invention (N=27).

[0162] [Table 19]

[0163] The results of the two tests above show a significant improvement in skin smoothness. The cream of the present invention significantly improves smoothness by 5.5% compared to placebo (p<0.05). This percentage clearly indicates an improvement on skins that are relatively young and slightly marked.

[0164] 3. Radiant skin

[0165] method The test was performed using a C-Cube™ color camera (Pixience). The camera uses constant, diffused LED illumination with polarization to avoid glare. Images are self-calibrated and homogenized. Structures smaller than 20 μm can be viewed with zoom. An algorithm combining colorimetric measurements and analysis of variance produces a brilliance index that correlates with the clinical evaluation method CLCT (Color Luminosity, Brightness, and Transparency). This index has a physiological window, established during the study between 35 and 70 units. The delta measured after application is expressed as a percentage of the physiological index measured at 35 units.

[0166] result Change in skin radiance; effect of the cream according to the invention (N=25).

[0167] [Table 20]

[0168] Note that after applying the cream of the present invention, skin radiance improved, with radiance increasing by +4.4% while the placebo sites worsened by an average of -2.7%. The difference is significant (p<0.05) in favor of the cream of the present invention compared to the placebo cream.

[0169] 4 / Skin tone and fatigue

[0170] method The Cutometer® MPA 580 (C&K) is used in a conventional manner to test the effect of cosmetic products on the viscoelastic parameters of the skin. The Cutometer measures the deformation and recovery of a skin area exposed to mechanical suction stress. The Cutometer allows the measurement of the skin's "fatigue" over time, so the possibility of applying several successive deformations was used. The assessment of extensibility (Uf) provides an index of skin tone / firmness. An internal study of 62 volunteers aged 23 to 81 years established a correlation between skin fatigue parameters and age, thereby providing a theoretical age increase.

[0171] result Skin fatigue and changes in color; effect of the cream according to the invention (N=27).

[0172] [Table 21]

[0173] [Table 22]

[0174] This table shows that application of the composition of the present invention can significantly reduce skin stretching, one of the signs of aging, thereby "relaxing" the skin by 5.6% and significantly reducing skin "fatigue" during repeated contractions by approximately 12%.

[0175] All the above in vitro and in vivo results show that the compositions according to the invention are undoubtedly interesting for cosmetic or dermatological treatments.

Claims

1. A cosmetic or dermatological composition comprising: - chrysin; - Rosmarinus officinalis extract; Pal-GQPR-OH (SEQ ID NO 2); and a physiologically acceptable medium, A composition consisting of:

2. The chrysin is present in a concentration ranging from 0.2 to 20,000 ppm by weight relative to the total weight of the composition. The composition of claim 1.

3. The Rosmarinus officinalis extract is present in a concentration ranging from 0.1 to 10,000 ppm by weight relative to the total weight of the composition. The composition according to claim 1 or 2.

4. The Pal-GQPR-OH (SEQ ID NO 2) is present in a concentration ranging from 0.5 to 50,000 ppm by weight relative to the total weight of the composition. The composition according to any one of claims 1 to 3.

5. Use of a composition according to any one of claims 1 to 4 for the non-therapeutic cosmetic treatment of the skin and / or its appendages.

6. 6. Use according to claim 5 for inhibiting or combating the effects of photoaging.

7. 7. Use according to claim 5 or 6 for antioxidant treatment.

8. Use according to any one of claims 5 to 7 for inhibiting and / or combating the harmful effects of blue light and / or for increasing the beneficial effects of blue light.

9. Use according to any one of claims 5 to 8 for improving the hydration, smoothness, radiance and / or tone of the skin.

10. The use according to any one of claims 5 to 9, wherein the treatment is local.

11. A composition according to any one of claims 1 to 4 for topical medical treatment.

Citation Information

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