USE OF ACTIVE INGREDIENTS FOR THE TREATMENT AND / OR PREVENTION OF SKIN SENESCENCE

Abstract

The present invention relates to a cosmetically or dermatologically effective amount of 8 oxoguanine glycosylase-1 or endonuclease and a Rhodomyrtus tomentosa fruit extract for reducing one or more signs of aging and for treating hormonal skin damage or for repairing skin damage caused by psychological stress in a human or animal patient. It also relates to a cosmetically or dermatologically effective amount of endonuclease and Rhodomyrtus tomentosa fruit extract for repairing DNA damage, helix-distorting, cyclobutane pyrimidine dimers (CPDs) caused by UVB exposure. Furthermore, cosmetic or dermatological compositions comprising 8 oxoguanine glycosylase-1 or endonuclease and a Rhodomyrtus tomentosa fruit extract are described as well as their cosmetic and / or dermatological use.

Description

Title of the invention: USE OF ACTIVE INGREDIENTS FOR THE TREATMENT AND / OR PREVENTION OF SKIN SENESCENCE CONTEXT OF THE INVENTION

[0001] The skin is the largest organ of the human and animal body, at the interface between the environment and internal organs. Thus, it is exposed to aggressions from both external sources (e.g., UV light, pollution, allergens, workplace and home environment) and from within the body.

[0002] Stress is a source of internal aggression that can cause inflammation, affect wound healing, and impact the condition of the skin. In response to chronic stress from work, relationships, and social interactions, the skin produces and is the target of stress hormones, which can make it vulnerable to inflammation, infection, and irritation. Skin glands tend to produce more sebum, resulting in acne breakouts. Stress can also cause flare-ups of eczema and psoriasis, interfere with skin regeneration, and accelerate skin aging by breaking down collagen and elastin and causing the appearance of fine lines and wrinkles. Finally, it can contribute to hair thinning and hair loss; while these effects are mostly temporary, they can, in the long term, cause irreversible damage.

[0003] Cortisol is a hormone naturally produced from the adrenal glands under the control of the pituitary gland and has a variety of health-related functions. Stress can lead to a sustained increase in cortisol levels, and a prolonged imbalance in these levels can have adverse effects on human or animal health. The same is true for corticosteroid therapy used to treat conditions such as rheumatoid arthritis, inflammatory bowel disease, asthma, allergies, to prevent organ rejection in transplant patients, and to treat patients with Alzheimer's disease. Symptoms of excessive cortisol synthesis include weight gain, thin, fragile skin that is slow to heal, and acne.

[0004] Adrenaline (epinephrine) is also a hormone produced by the adrenal glands. Its key role is to prepare the body for stressful or dangerous situations, which produce the adrenaline rush and then the "fight or flight" response.

[0005] The skin represents an extra-adrenal source of cortisol and adrenaline, products in keratinocytes. Both negatively affect keratinocyte motility, which results in impaired wound healing and skin regeneration in general, as well as a reduction in the properties of the skin barrier.

[0006] It is apparent from the above that it is highly desirable to have improved methods for countering the negative effects of stress on the skin.

[0007] 8-oxoguanine glycosylase-1, also known as OGGl, is a DNA glycosylase enzyme responsible for the excision of 8-oxoguanine (8-oxoG), a mutagenic base byproduct that results from exposure to reactive oxygen species (ROS) and other skin insults. The excision of 8-oxoguanine triggers the base excision repair (BER) pathway. Skin aging particularly reflects the accumulation of DNA damage from internal and environmental sources. It can be found in Arabidopsis thaliana extract or other sources such as plankton extract and is known to repair DNA damage caused by oxidative stress.

[0008] Myrtus communis, also commonly known as myrtle, is a plant in the Myrtaceae family. It is an evergreen shrub with white flowers and blue-black berries, native to the Mediterranean region of southern Europe but also found in Asia and the Indian subcontinent. Myrtle extract is rich in anthocyanins and flavonoids.

[0009] Rhodomyrtus tomentosa (also known as rose myrtle) is a flowering plant in the family Myrtaceae, native to southern and southeastern Asia, from India, eastern South China, Hong Kong, Taiwan and the Philippines, to southern Malaysia and Sulawesi. It grows on coasts, in natural forests, riverine areas, wetlands, rainforests and swampy areas, from sea level to an altitude of 2400 m. It is a popular ornamental plant, cultivated for its abundant flowers and sweet, edible fruits.

[0010] R. tomentosa has been used in traditional medicine to treat a variety of conditions such as dysentery, diarrhea, wounds, urinary tract infections, heartburn, and snake bites, as well as an antipyretic.

[0011] Micrococcus lysate is the end product of controlled lysis of different Micrococcus species. It contains an endonuclease with DNA repair activity. FIGURES

[0012] [Fig.l] illustrates the repair of cortisol-induced DNA damage in normal human keratinocytes, measured using the comet assay by i) a composition comprising 0.1% encapsulated Arabidopsis thaliana extract (approximately 0.0005% active agent based on the total composition), ii) a composition comprising 0.1% Rhodomyrtus tomentosa fruit extract (about 0.0005% active agent based on the total composition) and iii) a composition comprising 0.1% encapsulated Arabidopsis thaliana extract and 0.1% Rhodomyrtus tomentosa fruit extract. The result shows that the Arabidopsis thaliana extract and the Rhodomyrtus tomentosa fruit extract act synergistically. DETAILED DESCRIPTION OF THE INVENTION

[0013] Reference will now be made in detail to certain aspects of the disclosed subject matter, examples of which are illustrated in part in the accompanying drawings. While the disclosed subject matter will be described in conjunction with the enumerated claims, it will be understood that the disclosed subject matter illustrated in example is not intended to limit the claims to the disclosed subject matter.

[0014] Throughout this document, values ​​expressed in a range format should be flexibly interpreted to include not only the numerical values ​​explicitly stated as limits of the range, but also to include all individual numerical values ​​or subranges within that range as if each numerical value and subrange were explicitly stated. For example, a range of "about 0.1% to about 5%" or "about 0.1% to 5%" should be interpreted to include not only about 0.1% to about 5%, but also the individual values ​​(e.g., 1%, 2%, 3%, and 4%) and subranges (e.g., 0.1% to 0.5%; 1.1% to 2.2%; 3.3% to 4.4%) within the stated range. The statement "about X to Y" has the same meaning as "about X to about Y" unless otherwise stated.Similarly, the statement "about X, Y, or about Z" has the same meaning as "about X, about Y, or about Z" unless otherwise stated.

[0015] As used herein, the terms "a," "an," or "the" are used to include one or more than one, unless the context clearly indicates otherwise. The term "or" is used to refer to a non-exclusive "or" unless otherwise indicated. The phrase "at least one of A and B" or "at least one of A or B" has the same meaning as "A, B, or A and B." Furthermore, it is to be understood that phraseology or terminology used herein, and not otherwise defined, is for the purpose of description only and not of limitation.

[0016] The term "about" as used herein may allow for a degree of variability of a value or range, e.g., within 10%, 5%, or 1% of a stated value or stated limit of a range, and includes the exact stated value or range.

[0017] The term "substantially" as used herein refers to a majority, or substantially, as in at least about 50%; 60%; 70%; 80%; 90%; 95%; 96%; 97%; 98%; 99%; 99.5%; 99.9%; 99.99%; or at least about 99.999% or more; or 100%. The term "substantially free of" as used herein may mean having no or an insignificant amount of, such that the amount of material present does not affect the material properties of the composition comprising the material, such that about 0% by weight to about 5% by weight of the composition is the material, or about 0% by weight to about 1% by weight, or about 5% by weight or less, or an amount less than or equal to about 4.5% by weight; 4; 3.5; 3; 2.5; 2; 1.5; 1; 0.9; 0.8; 0.7; 0.6; 0.5; 0.4; 0.3; 0.2; 0.1; 0.01; or about 0.001% by weight or less, or about 0% by weight.

[0018] It will be understood that the term "comprises" and / or its variants when used in this specification will mean both "includes" and "consisting of".

[0019] The embodiments described in one aspect of the present invention are not limited to the described aspect. The embodiments may also be applied to another aspect of the invention, as long as the embodiments do not prevent those aspects of the invention from functioning in accordance with the intended purpose.

[0020] The present invention is based on the observation that the extract Arabidopsis thaliana extract and Rhodomyrtus tomentosa fruit extract behave synergistically on different models of stress-induced skin injury, particularly skin injury caused by sustained excessive levels of cortisol and / or adrenaline (epinephrine).

[0021] The present invention is also based on the observation that Micrococcus lysate and Rhodomyrtus tomentosa fruit extract can synergistically repair helix-distorting DNA damage to cyclobutane pyrimidine dimers (CPDs), caused in particular by exposure to UV light (e.g., UV-B).

[0022] Synergy is demonstrated, for example, if the combined effect of a given quantity of each of the two agents is greater than the weighted average of the effect of the same quantities of each of the two agents taken individually. The weighted average is calculated as follows:

[0023] [Math.l]

[0024] in which Wi represents the weight of component X;. For example, in [Fig.l] where both components were tested with the same amount (0.1%), w; is equal to 1 for both.

[0025] Therefore, the present invention relates to cosmetically or dermatologically effective, in particular synergistic, amounts of 8 oxoguanine glycosylase-1 and Rhodomyrtus tomentosa fruit extract for reducing one or more signs of skin aging.

[0026] The present invention also relates to cosmetically or dermatologically effective, in particular synergistic, amounts of oxoguanine glycosylase-1 and Rhodomyrtus tomentosa fruit extract for the treatment of hormonal skin damage and the repair of skin damage caused by psychological stress in a human or animal patient. Oxoguanine glycosylase-1 and Rhodomyrtus tomentosa fruit extract may be administered simultaneously or separately; in particular, oxoguanine glycosylase-1 may be administered simultaneously, before or after the Rhodomyrtus tomentosa fruit extract.

[0027] The present invention also relates to cosmetically or dermatologically effective, in particular synergistic, amounts of endonuclease and Rhodomyrtus tomentosa fruit extract for repairing helix-distorting DNA damage to cyclobutane pyrimidine dimers (CPDs) caused by UVB exposure.

[0028] Stress is the body's response to a psychological, physiological, or biological stressor such as a threat, difficulty, or obstacle. During a stressful situation, the body triggers the adrenal gland to produce two stress hormones, adrenaline and cortisol, so that their levels increase from baseline or resting levels to reactive levels. Under normal conditions, cortisol levels fall back to a basal level within 20 to 60 minutes. If cortisol levels remain elevated for longer durations, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 months, stress becomes chronic. Under stressful conditions, cortisol levels can increase up to 2 to 20 times the basal level, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 times the basal level.

[0029] The same considerations apply to adrenaline.

[0030] Sustained levels of cortisol and / or epinephrine can cause DNA damage, as measured using the comet assay, with the damage revealed by enzymatic treatment with FPG (formamidopyrimidine [fapy]-DNA glycosylase).

[0031] The formation of cyclobutane pyrimidine dimers (CPD) caused by UV exposure (especially UV-B) independently causes DNA damage, distorting the helix, which can also be revealed by the comet assay.

[0032] The comet assay (single-cell gel electrophoresis) is a simple method for measuring deoxyribonucleic acid (DNA) strand breaks in cells eukaryotes. Cells embedded in agarose on a microscope slide are lysed with detergent and high salt to form nucleoids containing supercoiled loops of DNA bound to the nuclear matrix. High pH electrophoresis produces comet-like structures, observed by fluorescence microscopy; the intensity of the comet's tail relative to the head reflects the number of DNA breaks.

[0033] It has been found that DNA damage caused by sustained levels of cortisol and / or adrenaline (epinephrine) or by exposure to UV light can be treated with cosmetically or dermatologically effective, in particular synergistic, amounts of oxoguanine glycosylase-1 and Rhodomyrtus tomentosa fruit extract or with cosmetically or dermatologically effective, in particular synergistic, amounts of endonuclease and Rhodomyrtus tomentosa fruit extract.

[0034] The oxoguanine glycosylase-1 or endonuclease and Rhodomyrtus tomentosa fruit extract may be present in a dermatologically or cosmetically effective amount in a range of 0.00001% to 10%, generally 0.0001% to 1%, more generally 0.0005 to 0.5% or 0.001% to 0.01% or in any amount obtained by multiplying these values ​​by 2, 3, 4, 5, 6, 7, 8, 9. The amount of oxoguanine glycosylase-1, endonuclease and Rhodomyrtus tomentosa fruit extract is not necessarily the same, and each of the above values ​​is described separately for oxoguanine glycosylase-1, endonuclease and Rhodomyrtus tomentosa fruit extract. tomentosa.Suitable cosmetically or dermatologically effective, in particular synergistic, amounts of oxoguanine glycosylase-1, endonuclease and Rhodomyrtus tomentosa fruit extract may be determined by the person skilled in the art by means known in the art of cosmetic and dermatological formulation. The amounts may also be determined for each patient based on their individual characteristics and condition.

[0035] A composition according to the present invention is preferably intended for topical administration. When the cosmetic composition is a topical formulation, it may be an O / W emulsion, a W / O emulsion, microemulsions or multiple emulsions such as a cream, a lotion, a gel, a serum, a spray, a mask, a cleanser, a micellar water, a self-tanning product, an oil (single phase or multi-phase), a sunscreen product, all conventional face and body care treatments, a solution, an ointment, a paste, an aerosol foam, a powder, a solid or a transdermal patch.

[0036] A cosmetic composition according to the present invention comprises oxoguanine glycosylase-1 or endonuclease and Rhodomyrtus tomentosa fruit extract (hereinafter also referred to as API), as well as any formulation additive known in the art of formulating topical dermatological or cosmetic compositions.

[0037] The active agent of Arabidopsis thaliana extract is considered to be 8- oxoguanine glycosylase-1 and the active agent of Micrococcus lysate is considered to be an endonuclease. Therefore, in the present application, these terms are used interchangeably: the use of the expression Arabidopsis thaliana extract does not exclude the use of 8-oxoguanine glycosylase-1 from other sources, and the use of the expression Micrococcus lysate does not exclude the use of the same endonuclease from other sources.

[0038] Excipients used in topical formulations are well known in the art and examples can be found in the Handbook of Pharmaceutical Excipients (Rowe, RC et al., APhA Publications; 5th ed., 2005). Classes of excipients may include waxes, emollients, thickening agents / viscosity increasing agents, humectants, pH modifiers, water repellents, antifoaming agents, surfactants, solubilizers, wetting agents, penetration enhancers, antioxidants, and solvents. Excipients may also be present in the topical composition at any suitable concentration. In some embodiments, the topical composition comprises excipients at a concentration in a range of 70 to 99.99% by weight.

[0039] The carrier of the cosmetic composition may be a clay or a liposome. Examples of suitable clays may include bentonite, hectorite, stearalkonium hectorite and propylene carbonate, rhassoul clay, French green clay, Fuller's earth clay, yellow clay or a mixture thereof. Stearalkonium hectorite in combination with propylene carbonate is preferred.

[0040] Liposomes are considered the most commonly used nanocarriers for various potentially active hydrophobic and hydrophilic molecules due to their high biocompatibility, biodegradability, and low immunogenicity. Liposomes have also demonstrated an ability to enhance the solubility and regulated distribution of drugs, as well as their surface modification capability for targeted delivery into the skin, sustained and long-lasting release. Based on this composition, liposomes can be considered to have evolved from conventional, long-circulating, targeted, and immune liposomes to stimuli-responsive and actively targeted liposomes. Many liposome-based drug delivery systems are currently clinically approved to treat several diseases, such as cancer, fungal and viral infections; more liposomes have reached advanced stages in clinical trials. According to their structures, liposomes are classified into four categories based on the size and number of bilayers: small unilamellar vesicles (SUVs), large unilamellar vesicles (LUVs), multilamellar vesicles (MLVs), and multivesicular vesicles (MWs). Liposomes have a monophospholipid bilayer in a unilamellar structure, while they have an onion-like structure in a multilamellar structure. MWs form a multilamellar arrangement with concentric phospholipid spheres since many unilamellar vesicles are produced within larger liposomes. Vesicle size is an important factor that regulates the circulating half-life of liposomes. Both the size and the number of bilayers influence the amount of encapsulated drug.The interaction of liposomes with the cell membrane is represented by various theories: specific (receptor-mediated) or nonspecific endocytosis, local fusion (adhesion), phagocytosis, and uptake into the cell membrane. Liposome-cell interactions are influenced by a variety of factors, including composition, liposome diameters, surface charge, targeting ligand on the liposome surface, and the biological environment.

[0041] An example of a liposome useful in the context of the present invention is described in document EP 2 163 236, in particular Example 1, the specific content of which is included by way of reference herein. The base composition may in particular comprise shell liposomes whose particle size is 250 and 600 nm and whose viscosity in a hydrogel is between 4,000 and 20,000 nPa*s, and which comprise in their aqueous phase at least two internal liposomes, each of which comprises a different active agent of the invention, whereby the internal liposomes have a particle size of between 50 and 200 nm.

[0042] Based on the total concentration of the cosmetic composition, the carrier is in a range of about 0.01 wt% to about 70 wt%; about 20 wt% to about 50 wt%; an amount less than, equal to, or greater than about 0.01 wt%; 0.5; 1; 1.5; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 30; 31; 32; 33; 34; 35; 36; 37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47; 48; 49; 50; 51; 52; 53; 54; 55; 56; 57; 58; 59; 60; 61; 62; 63; 64; 65; 66; 67; 68; 69; or about 70% in weight.

[0043] Another example of liposomes are cationic liposomes. Cationic liposomes are liposomes having a positive charge on their outer surface, the composition of which is known in the art. Typical microvesicles are composed of phospholipids, including sphingomyelin, phosphatidylcholine and / or cholesterol, but may also include other lipids such as those present in eggs and phosphatidylcholine as long as they are compatible with the bilayer structure.

[0044] The membrane bilayer may comprise or be coated with cationic lipids to impart the positive charge to the outer surface of the microvesicle. Examples of such lipids are cetyl betaine, myristyl betaine, behenyl betaine, stearyl betaine, lauryl betaine, laurylpyridinium chloride, cetylpyridinium chloride, steapyrium chloride, stearalkonium chloride, lauryl methyl gluceth-10 hydroxypropyldimonium chloride, PEG-5 stearyl ammonium chloride, didecyldimonium chloride, distearoylethyl dimonium chloride, lauralkonium chloride, benzalkonium chloride, lauryl isoquinolinium bromide, domiphene bromide, tricetylmonium chloride, distearyldimonium chloride and hydroxypropylbisstearyldimonium chloride. Preferred lipids are cetylpyridinium chloride, benzalkonium chloride, distearyldimonium chloride or didecyldimonium chloride.

[0045] The membrane bilayer may comprise other optional components such as bulking agents such as mannitol and glycine, thickening agents such as glycerin and / or cetearyl alcohol, metal hydroxides such as sodium hydroxide, preservatives such as potassium sorbate and / or sodium benzoate and alcohols.

[0046] The positively charged microvesicles can be used as such for the administration of synergistic compositions, according to the present invention, to cells, in particular to skin cells.

[0047] Alternatively, they can be used to prepare exosome-like vectors. In particular, the positive charge on the surface of liposomes can be used to functionalize microvesicles through electrostatic interactions with appropriate ligands. These ligands function to facilitate communication between cells and the transfer of material, particularly in skin cells.

[0048] Particularly effective ligands belong to the class of oligopeptides and polypeptides which play a key role in the regulation of physiological processes and have biomimetic sequences similar to those produced and secreted by skin cells such as fibroblasts, keratinocytes and melanocytes.

[0049] The texturizing agent (emollient) may comprise a mixture of dicaprylyl carbonate and tocopherol, a mixture of caprylic / capric triglyceride, a mixture of caprylic / capric triglyceride and castor oil / ipdi copolymer, or a combination thereof. Additional examples of emollients include mono-, di-, and tri-glycerides and butters and hydrogenated versions of seed and nut oils including, but not limited to; palm oil, coconut, vegetable oil, avocado oil, rapeseed oil, corn oil, soybean oil, sunflower oil, safflower oil, Limnanthes douglasii seed oil, blueberry seed oil, watermelon seed oil, olive oil, cranberry, macadamia nut oil, argan oil, pomegranate oil, Moroccan argan oil, blueberry oil, raspberry oil, walnut oil, pecan oil, peanut oil, bay oil, mango seed oil, square pea oil, castor oil; shea butter, jojoba oil, hydrolyzed jojoba oil, carnauba butter, carnauba wax, stearyl heptanoate succinate castor isostearate, cetyl ricinoleate, oleyl fructate, sucrose monostearate, sucrose distearate, sucrose tristearate, sucrose tetrastearate, candelabra cera, glycine soja (soybean) wax, rapeseed wax, palm wax, beeswax, petrolatum, myristyl myristate, oleyl erucate, squalane, stearyl alcohol,cetearyl isononanoate, polyisobutene, glyceryl stearate, glyceryl distearate, cetyl alcohol, lanolin, lanolin ethoxylate, low molecular weight polyethylene waxes, low molecular weight polypropylene waxes, PEG-30 glyceryl cocoate, PEG-80 glyceryl cocoate, glyceryl stearate, PEG-8 ricinoleate, PEG-8 raspberryate, linear (also known as bis) and pendant versions of including hydroxyl-terminated and methyl ether-terminated; PEG-3 to PEG-32 dimethicone (including but not limited to: PEG-3 dimethicone, PEG-9 dimethicone, PEG-10 dimethicone, PEG-11 dimethicone, methyl ether dimethicone, PEG-12 dimethicone, PEG-14 dimethicone, PEG-17 dimethicone, dimethicone of PEG), bis-PEG / PPG-20 / 20 dimethicone, PEG / PPG 20 / 23 dimethicone, PEG / PPG 20 / 22 dimethicone, butyl ether dimethicone, PEG / PPG 23 / 6 dimethicone,PEG / PPG 20 / 15 dimethicone. Alkyl Modified Dimethicone (Stearoxy Dimethicone, Behenoxy Dimethicone, Cetyl Dimethicone, Cetearyl Methicone C30-45 Alkyl Cetearyl Dimethicone Copolymer, Alkyl Dimethicone, Caprylyl Methicone, PEG-8 Dimethicone / Dimer Dilinoleic Acid Copolymer, Bis-PEG-10 Dimethicone / Dimer Dilinoleate Copolymer, Stearoxymethicone / Dimethicone Copolymer, Diphenyl Dimethicone, Lauryl Polyglycerol-3 Polydimethylsiloxyethyl Dimethicone, PEG-9 Lauryl Polydimethylsiloxyethyl Dimethicone), Dimethicone Fluid (>20 est), Quaternized Ammonia Silicone Polymers, Amino Silicones, Silicone Quaternium-18, Amodimethicone, Phenyl Trimethicone, amino silicone polyethers, polyglycerol-3 disiloxane dimethicone, polyglycerol-3 polydimethylsiloxyethyl dimethicone, silica dimethyl silylate, bambusa arundinacea, and PEG-9 polydimethylsiloxyethyl dimethicone. ,

[0050] Based on the total concentration of the cosmetic composition, the texturizing agent is in a range of about 10% by weight to about 60% by weight; about 20% by weight to about 40% by weight; in an amount less than, equal to, or greater than about 10% by weight; 11; 12; 13; 14; 15; 16; 17; 18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 30; 31; 32; 33; 34; 35; 36; 37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47; 48; 49; 50; 51; 52; 53; 54; 55; 56; 57; 58; 59; or about 60% by weight.

[0051] Antioxidants slow down, protect against, and promote repair of the undesirable effects of oxidative degradation. The antioxidant may comprise a mixture of diethylhexyl syringylidenemalonate and caprylic / capric triglyceride, or a combination thereof. Other antioxidants include vitamin C and its derivatives, niacinamide, resveratrol, vitamin E and its derivatives, retinol and its derivatives, coenzyme Q10, as well as polyphenols and diethylhexyl syringylidenemalonate. Based on the total concentration of the cosmetic composition, the antioxidant is in a range of about 0.05% by weight to about 20%; from about 5% by weight to about 15% by weight; in an amount less than, equal to, or greater than 2% by weight;3;4;5;6;7;8;9;10;11;12; 13; 14; 15; 16; 17; 18; 19; or about 20% by weight.

[0052] Any suitable humectant or combination of humectants may be used. Examples include glycols such as diethylene glycol monoethyl ether, glycerols; sugar polyols such as sorbitol, xylitol, and maltitol; polyols such as polydextroses; and mixtures thereof. In particular examples, the humectant comprises an alkylene glycol, such as hexylene glycol.

[0053] In some embodiments, the topical compositions comprise at least one oil. Suitable oils include silicones (such as dimethicone), hydrocarbons, esters, amides, ethers, and mixtures thereof.

[0054] The compositions of the invention may comprise one or more of the following cosmetic products as additives: acetyl hexapeptide-3 (argireline), acrylate / C10-30 alkyl acrylate crosspolymers, Actinidia deliciosa (kiwi) seed oil, algae extract, Andropogon zizanioides (vetiver) essential oil, Aniba rosaeodora (rosewood) essential oil, apricot kernel oil, Arctostaphylos uva ursi extract, Argania spinosa (argan) oil, argireline, astaxanthin, beta glucan, Borago officinalis (borage) oil, Boswellia carterii (frankincense) essential oil, Caesalpinia spinosa (tara) gum, calcium carbonate, Camellia oleifera (camellia) oil, Camellia sinensis, Cannabis sativa seed oil (hemp), caprylic / capric triglyceride, Carica papaya (papaya) seed oil, cellulose gum, Centella asiatica (tiger grass) extract, ceramide 1, ceramide 3, ceramide 6, ceramide complex,Cetearyl glucoside, chitin, chitosan, cholecalciferol (vitamin D3), cholesterol, Citrullus lanatus (watermelon) extract, Citrus aurantium (neroli) hydrosol, Citrus essential oil, paradisi (grapefruit) fruit, Cocos nucifera (coconut) oil, coenzyme Q10, Crithmum maritimum (sea fennel) extract, decyl polyglucoside, dipeptide diaminobutyroyl benzylamide diacetate (snake venom peptides), elastin, Enteromorpha compressa extract, fatty acids, gamma-oryzanol, geranylgeranone gga, gluconolactone, glucosamine, glycan enhancer, tetradecyl aminobutyroyl valyl-aminobutyric acid urea trifluoroacetate, glycerin, Glycine soja (soybean) oil, glycoproteins, Glycyrrhiza glabra (licorice root) extract, green tea extract, Gynostemma pentaphyllum (gynostemma) extract, Haematococcus pulvialis, Helianthus annuus (sunflower) seed oil, Homeostatin, Hyaluronic Acid, Hydrolyzed Rice Bran Extract, Hydroquinone, Lactoceramides, Lavendula Essential Oil angustfolia (lavender), lecithin, Leontopodium alpinum (edelweiss) extract, linoleic acid, magnesium ascorbyl phosphate, magnesium chloride, matrix peptides, mixed tocopherols (vitamin E), Morus alba (blackberry) root extract, niacinamide, noni, non-nano zinc oxide, oat beta-glucans, oil & Oenothera biennis (evening primrose), oleic acid, omega-6 fatty acids, omega-9 fatty acids, omega-3 fatty acids, Oryza sativa (rice) bran oil, palmitic, palmitoyl tripeptide-5, Passiflora incarnate (passion fruit) oil, pearl powder, Persea gratissima (avocado) oil, phytosphingosine, Pinus densiflora (red pine needle) oil, Plantago species (plantain) leaf extract, essential oil of Polianthes tuberosa (tuberose), polyaminopropyl biguanide (cosmocil CQ), polyglucose / lactylate, Populus tremuloides (aspen) bark extract, potassium sorbate, Prunus armeniaca (apricot) kernel oil, pullulan,Red algae, red raspberry seed oil, resveratrol, retinyl palmitate (retinol), Rosa centifolia (rose) essential oil, Rosa rubignosa (rosehip) seed oil, Rosmarinus officinalis (rosemary) oleoresin, Rubus idaeus (raspberry) seed oil, saccharomyces ferment, Salvia seed oil, hispanica (chia) oil, Sclerocarya birrea (marula) oil, kelp extract, Sesamum indicum (sesame) seed oil, Simmondsia chinensis (jojoba) oil, SOD, sodium alginate, sodium benzoate, sodium hyaluronate, sodium lauroyl lactylate, soy peptides, soy rice peptides [oxidoreductase], squalene, sucrose cocoate, Tamarindus indica (tamarind) seed extract, teprenone, thioctic (alpha lipoic) acid, Trachelospermum jasminoides (star jasmine) essential oil, tripeptide-29, tripeptides, ubidecarenone, undecylenoylphenylalanine, vitamin A, vitamin C, Vitus vinifera (grape) seed oil, watermelon seed oil, white tea extract, xanthan gum and fermented black tea extract xylitol (kombucha). The additive may include creatine and / or bifida ferment lysate.

[0055] A composition according to the invention may further comprise a UV filter. According to various aspects of the present invention, the one or more UV filters comprise a UV-A filter, a UV-B filter, a broadband UV-A + UV-B filter, or a mixture thereof. In certain aspects, the UV-A filter is selected from: - butyl methoxydibenzoylmethane or l-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane- 1, 3 -dione, - terephthalylidene dicamphor sulfonic acid or 3,3'-(1,4-phenylenedimethylene) bis (7,7-dimethyl-2-oxobicyclo[2.2.l]hept-1-ylmethanesulfonic acid) and its salts, - menthyl anthranilate, - disodium bisdisulizole or disodium phenyl dibenzimidazole tetrasulfonate, - diethylamino hydroxybenzoyl hexyl benzoate, and - dimethoxyphenyl-[l-(3,4)]-4,4-dimethyl 1,3-pentanedione.

[0056] In some aspects, the UV-A filter is butyl methoxydibenzoylmethane. In some aspects, the three UV-B filters are independently selected from: - 3-benzylidene camphor, - benzylidene camphor sulfonic acid, - benzacamene or 4-methylbenzylidene camphor or 4-MBC, - 2-ethoxyethyl p-methoxycinnamate, - DEA methoxycinnamate, - iscotrizinol or diethylhexyl butamido triazone or 4,4-{[6-[[[(l, 1 -dimethylethyl)amino]carbonyl]phenyl]amino]-l,3-5-triazine-2,4-diyl]diimino}bis-, bis(2-ethylhexyl)benzoic acid ester, - digalloyl trioleate, - diisopropyl methyl cinnamate, - Ethyl dihydroxypropyl PABA, - dimethoxy benzylidene dioxoimidazoline ethylhexyl propionate, - octyl dimethyl PABA or 2-ethylhexyl 4-(dimethylamino)benzoate, - octyl methoxycinnamate or 2-ethylhexyl 4-methoxycinnamate, - octyl salicylate or 2-ethylhexyl salicylate, - octyl triazone or ethylhexyl triazone or 2,4,6-trianilino-(p-carbo-2'-ethylhexyl-1'-oxy)-1,3,5-triazine, - ferulic acid, glyceryl dimethoxycinnamate ethylhexanoate, - Glyceryl PABA, - 2-hydroxy-3,3,5-trimethylcyclohexyl ester of benzoic acid, - isoamyl p-methoxycinnamate or isopentyl 4-methoxycinnamate, - isopentyl trisiloxane trimethoxycinnamate, - isopropyl benzyl salicylate, - isopropyl methoxycinnamate, - lawsone + dihydroxyacetone, - 4-methylbenzylidene camphor, - 2-cyano-3,3-diphenyl acrylic acid 2-ethylhexyl ester, - aminobenzoic acid (PABA), PEG-25 PABA, - Pentyl dimethyl PABA, - phenylbenzimidazole sulfonic acid or 2-phenylbenzimidazole-5- acid sulfonic acid and its potassium, sodium and triethanolamine salts, - polyacrylamido methylbenzylidene camphor, poly silicone-15 or dimethicodiethyl benzalmalonate, - salicylic acid, and - TEA salicylate (trolamine salicylate). In some aspects, the broadband UV-A and UV-B filter is selected from: - benzophenone, - benzophenone-1, - benzophenone-2, - benzophenone-3 or 2-hydroxy-4-methoxybenzophenone, - benzophenone-4 or 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (benzophenone-5) and its sodium salt, - benzophenone-5, - benzophenone-6, - dioxybenzone (benzophenone-8), - benzophenone-9, - beta-2-glucopyranoxy propyl hydroxy benzophenone, - bemotrizinol or bis-ethylhexyloxyphenol methoxyphenyl triazine or 2,2'- (6-(4-methoxyphenyl)-1,3,5-triazine-2,4-diyl)bis(5-((2-ethylhexyl)oxy)ph enol), - drometrizole, - drometrizole trisiloxane or phenol, 2-(2H-benzotriazol-2-yl)-4-methyl-6-(2- methyl-3-(l,3,3,3-tetramethyl-l-(trimethylsilyl)oxy)-disiloxanyl)propyl, - bisoctrizol or methylene bis-benzotriazolyl tetramethylbutylphenol, - titanium dioxide and zinc oxide.

[0057] In some aspects, each of the UV filters in the sunscreen composition is present in an amount of about 0.1 wt% to about 25 wt%, about 0.1 wt% to about 20 wt%, about 0.1 wt% to about 18 wt%, 0.1 wt% to about 15 wt%, about 0.1 wt% to about 12 wt%, or about 0.1 wt% to about 15 wt%. % by weight, about 0.1% by weight to about 10% by weight, about 0.1% by weight to about 8% by weight, about 0.1% by weight to about 6% by weight, the weight percentage being based on the total weight of the sunscreen composition.

[0058] In some aspects, the sunscreen composition comprises less than about 35% by weight of UV filters. In some aspects, the sunscreen composition comprises between about 5% by weight and about 25% by weight of UV filters. In some aspects, the sunscreen composition comprises about 20% by weight of UV filters.

[0059] In certain embodiments of the invention, the topical compositions may have a viscosity increasing agent concentration in a range of 0.5 to 30% by weight, a solvent concentration in a range of 50 to 90% by weight, and a humectant concentration in a range of 2 to 20% by weight.

[0060] In certain embodiments, synergistic compositions according to the present invention further comprise at least water, one or more oils, one or more mono- and / or polyhydroxyalcohols, one or more preservatives, one or more emulsifiers, one or more absorption promoters and one or more perfumes.

[0061] Hormonal damage can result in acne, eczema, psoriasis, rosacea, rashes, hives.

[0062] The compositions according to the invention can be used for the treatment, reduction, and / or prevention of hormonal skin damage or signs of skin aging, in particular when it is one or more of acne, eczema, psoriasis, rosacea, rashes, hives, fine lines or wrinkles; reduction of skin pore size; improvement of skin thickness, plumpness and / or tone; improvement of skin smoothness, fineness and / or suppleness; improvement of skin tone, radiance, and / or clarity; improvement of procollagen, and / or collagen production; improvement of elastin maintenance and remodeling; improvement of skin texture and / or promotion of retexturing; improvement of skin barrier repair and / or function; improvement of the appearance of skin contours; restoration of skin radiance and / or luminosity;replenishing nutrients and / or essential constituents of the skin; improving the appearance of skin diminished by aging and / or menopause; improving skin hydration; increasing skin elasticity and / or resilience; treating, reducing, and / or preventing sagging skin; improving skin firmness; reducing pigmentation spots and / or mottled skin; and improving the optical properties of the skin by diffraction or reflection of light. EXAMPLES

[0063] The following examples are intended to further illustrate certain embodiments of the invention and are not intended to limit the scope of the invention in any way. Example 1

[0064] Normal human keratinocytes were treated with a 5 μM cortisol solution for 24 h. The cortisol was then removed and the cells were treated with the composition for 5 min, 10 min, 20 min, 30 min. DNA damage was assessed using the comet assay, with oxidative damage revealed by enzymatic treatment with FPG (Formamidopyrimidine [fapy]-DNA glycosylase). DNA damage was expressed by Chi-2 Olive Tail Moment (Chi2 OTM). Example 2

[0065] Example composition

[0066] [Tables 1] component Qty Water QSP 100 ARABIDOPSIS THALIANA EXTRACT 0.00001% to 1% RHODOMYRTUS 0.00001% to 1% Glycerin 5 Ethylhexyl Palmitate 3 Coco-Caprylate / Caprate 2 Glyceryl Stearate 1.75 PEG-100 Stearate 1.75 Sodium Polyacrylate 0.6 Sodium Benzoate 0.45 Xanthan Gum 0.2 Chlorphenesin 0.2 Total up to 100

Claims

Claims

1. A cosmetically or dermatologically effective amount of 8 oxoguanine glycosylase-1 or endonuclease and Rhodomyrtus tomentosa fruit extract for reducing one or more signs of aging.

2. A cosmetically or dermatologically effective amount of 8 oxoguanine glycosylase-1 and Rhodomyrtus tomentosa fruit extract for use in the treatment of hormonal skin damage or for repairing skin damage caused by psychological stress in a human or animal patient.

3. Cosmetically or dermatologically effective amount of endonuclease and Rhodomyrtus tomentosa fruit extract for repairing helix-distorting DNA damage to cyclobutane pyrimidine dimers (CPDs) caused by UVB exposure.

4. A cosmetically or dermatologically effective amount according to any preceding claim, wherein the 8 oxoguanine glycosylase-1 and Rhodomyrtus tomentosa fruit extract or the endonuclease and Rhodomyrtus tomentosa fruit extract are administered simultaneously or separately.

5. A cosmetically or dermatologically effective amount according to claim 4, wherein the 8 oxoguanine glycosylase-1 or endonuclease is administered separately, before or after the Rhodomyrtus tomentosa fruit extract.

6. A cosmetically or dermatologically effective amount according to any preceding claim, wherein the sign of aging, skin damage caused by psychological stress or hormonal damage is caused by high stress over a long period of time.

7. A cosmetically or dermatologically effective amount according to any preceding claim, wherein the sign of aging or hormonal damage is caused by sustained excessive levels of cortisol and / or adrenaline (epinephrine) in keratinocytes and / or fibroblasts.

8. A cosmetically or dermatologically effective amount according to any preceding claim, wherein the sign of aging is caused by deformation of DNA helix induced by the formation of cyclobutane pyrimidine dimers (CPD).

9. A cosmetically or dermatologically effective amount according to claim 7 or 8, wherein the sign of aging or hormonal injury is one of acne, eczema, psoriasis, rosacea, rashes, hives, wrinkles or fine lines, reduction in skin pore size, improvement in skin thickness, plumpness and / or tone; improvement in skin smoothness; improvement in skin tone, radiance and / or clarity; improvement in procollagen and / or collagen production; improvement in elastin maintenance and remodeling; improvement in skin texture and / or promotion of retexturing; improvement in skin barrier repair and / or function; improvement in the appearance of skin contours; restoration of skin radiance and / or luminosity; replenishment of nutrients and / or essential components of the skin;improving the appearance of skin diminished by aging and / or menopause; improving skin hydration; increasing skin elasticity and / or resilience; treating, reducing, and / or preventing sagging skin; improving skin firmness; reducing pigmentation spots and / or blotchy skin; and improving the optical properties of skin by diffraction or reflection of light.;

10. A dermatological or cosmetic composition comprising cosmetically or dermatologically effective amounts of 8 oxoguanine glycosylase-1 or endonuclease and Rhodomyrtus tomentosa fruit extract.

11. The composition of claim 10, wherein the composition is for topical administration.

12. A composition according to claim 10 or 11, wherein the composition is a solution, lotion, cream, ointment, gel, paste, foam or aerosol spray, powder, solid or transdermal patch.

13. Composition according to one of claims 10 to 12, further comprising water, one or more oils, one or more mono- and / or polyhydroxy-alcohols, one or more preservatives, one or more emulsifiers, one or more absorption promoters and one or more perfumes.

14. A composition according to any one of claims 10 to 13, wherein the amount of each of 8-oxoguanine glycosylase, endonuclease and Rhodomyrtus tomentosa fruit extract is in the range of 0.00001% to 10% based on the total weight of the composition.

15. A composition according to any one of claims 10 to 14, further comprising bifida ferment lysate and / or creatine.

16. A composition according to any one of claims 10 to 15, further comprising lecithin.

17. Composition according to any one of claims 10 to 16, further comprising a UV filter.

18. A composition according to any one of claims 10 to 17 in the form of a liposome, wherein the composition preferably also comprises a phytolase and / or an alkyltransferase.

19. A composition according to any one of claims 10 to 18, wherein the 8 oxoguanine glycosylase-1 or endonuclease and the Rhodomyrtus tomentosa fruit extract are present in synergistic amounts.

20. A composition according to any one of claims 10 to 19, for use according to any one of claims 1 to 3 and 6 to 9.

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