Use of active ingredients for treating and / or preventing skin senescence

Abstract

The present invention relates to a cosmetically or dermatologically effective amount of 8 oxoguanine glycosylase-1 or endonuclease and of Rhodomyrtus tomentosa Fruit Extract for reducing one or more signs of ageing and for the treatment of hormonal skin damage or to repair damage to the skin caused by psychological stress in a human or animal patient. It further relates to a cosmetically or dermatologically effective amount of endonuclease and Rhodomyrtus tomentosa Fruit Extract to repair cyclobutane pyrimidine dimers (CPD) helix-distorting DNA damage caused by UVB exposure. Moreover cosmetic or dermatological compositions comprising 8 oxoguanine glycosylase-1 or endonuclease and Rhodomyrtus tomentosa Fruit Extract are disclosed as well as their cosmetic and / or dermatological use.

Description

USE OF ACTIVE INGREDIENTS FOR TREATING AND / OR PREVENTING SKIN SENESCENCE CLAIM OF PRIORITY

[0001] This patent application claims the benefit of priority to French Application Serial No.2403150, filed March 28, 2024, which is incorporated by reference herein in its entirety. BACKGROUND OF THE INVENTION

[0002] The skin is the largest organ of the human and animal body, at the interface between the environment and the internal organs. As such, it is exposed to insults coming from both external sources (e.g. UV light, pollution, allergens, occupational and household settings) and from within the body.

[0003] One source of internal insult is stress, which can cause inflammation, affect wound healing, and impact skin conditions. In reaction to chronic stress from work, relationships and social interactions the skin both produces and is a target of stress hormones, which can make the skin vulnerable to inflammation, infection and irritation. Skin glands tend to produce more sebum, which manifests itself in outbreaks of acne. Stress can also cause flares of eczema and psoriasis and can interfere with skin regeneration and accelerate skin ageing by breaking down collagen and elastin and causing the appearance of wrinkles and fine lines. Finally, it can contribute to hair thinning and loss; while these effects are mostly temporary, on the long run they can cause irreversible damage.

[0004] Cortisol is a hormone naturally produced from the adrenal glands under the control of the pituitary gland and has a plethora of functions related to health. Stress can cause a sustained increase in cortisol levels, and a prolonged imbalance in cortisol levels can have undesired effects on human or animal health. Similarly in case of corticosteroid therapy used to treat conditions like rheumatoid arthritis, inflammatory bowel disease, asthma, allergies, to prevent organ rejection in transplant patients and to treat Alzheimer’s patients. Symptoms of excessive cortisol synthesis are weight gain, thin and fragile skin that is slow to heal, and acne.

[0005] Adrenaline (epinephrine) is also a hormone produced by the adrenal glands. Its key role is to prep the body for stressful or dangerous situations, which produce the so-called adrenaline rush and in turn the “fight or flight” reaction.

[0006] The skin represents an extra-adrenal source of both cortisol and adrenaline, which are produced in keratinocytes. Both negatively affect keratinocyte motility, which in turn can be seen in impaired wound healing and skin regeneration in general, as well as decreased skin barrier properties.

[0007] From the discussion above it is apparent that improved methods to counter the negative effects of stress on skin are highly desirable.

[0008] 8-Oxoguanine glycosylase-1, also known as OGG1, is a DNA glycosylase enzyme that is responsible for the excision of 8-oxoguanine (8-oxoG), a mutagenic base byproduct that occurs as a result of exposure to reactive oxygen species (ROS) and other skin insults. Excision of 8-oxoguanine initiates the base excision repair (BER) pathway. Skin aging in particular reflects the accumulation of damage to DNA from both internal and environmental sources. It can be found in Arabidopsis thaliana extract or other sources like plankton extract and is known to act by repairing DNA damage caused by oxidative stress.

[0009] Myrtus communis, also commonly known as Myrtle, is a plant of the family of Myrtaceae. It is an evergreen shrub with white flowers and blue-black berries native to the Mediterranean region in Southern Europe but found in Asia and the Indian subcontinent. The myrtle extract is rich in anthocyanins and flavonoids.

[0010] Rhodomyrtus tomentosa (also known as rose myrtle) is a flowering plant in the family Myrtaceae, native to southern and southeastern Asia, India, east to southern China, Hong Kong, Taiwan and the Philippines, and south to Malaysia and Sulawesi. It grows in coasts, natural forest, riparian zones, wetlands, moist and wet forests, bog margins, from sea level up to 2400 m elevation. It is a popular ornamental plant and is grown for its abundant flowers and sweet, edible fruit.

[0011] R. tomentosa has been used as traditional medicine to treat a variety of conditions such as dysentery, diarrhoea, wounds, urinary tract infections, pain heartburn and snake bites, and as antipyretic.

[0012] Micrococcus Lysate is the end product of the controlled lysis of various species of Micrococcus. It contains endonuclease with DNA repair activity.FIGURES

[0013] Fig 1 illustrates the repair of cortisol-induced DNA damage of normal human keratinocytes as measured with the Comet Assay by i) a composition comprising 0.1% encapsulated Arabidopsis thaliana extract (about 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 show that Arabidopsis thaliana extract and Rhodomyrtus tomentosa fruit extract act synergistically. DETAILED DESCRIPTION OF THE INVENTION

[0014] 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 exemplified subject matter is not intended to limit the claims to the disclosed subject matter.

[0015] Throughout this document, values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a range of “about 0.1% to about 5%” or “about 0.1% to 5%” should be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. The statement “about X to Y” has the same meaning as “about X to about Y,” unless indicated otherwise. Likewise, the statement “about X, Y, or about Z” has the same meaning as “about X, about Y, or about Z,” unless indicated otherwise.

[0016] In this document, the terms “a,” “an,” or “the” are used to include one or more than one unless the context clearly dictates otherwise. The term “or” is used to refer to a nonexclusive “or” unless otherwise indicated. The statement “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.” In addition, it is to be understood that the phraseology or terminology employed herein, and not otherwise defined, is for the purpose of description only and not of limitation.

[0017] The term “about” as used herein can allow for a degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of a stated value or of a stated limit of a range and includes the exact stated value or range.

[0018] The term “substantially” as used herein refers to a majority of, or mostly, 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 can mean having none or having a trivial amount of, such that the amount of material present does not affect the material properties of the composition including the material, such that about 0 wt% to about 5 wt% of the composition is the material, or about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than or equal to about 4.5 wt%, 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 wt% or less, or about 0 wt%.

[0019] It will be further understood that the terms “comprises” and / or variations thereof when used in this specification shall mean both “includes” and “consists of”.

[0020] The embodiments described in one aspect of the present invention are not limited to the aspect described. The embodiments may also be applied to a different aspect of the invention as long as the embodiments do not prevent these aspects of the invention from operating for its intended purpose.

[0021] The present invention is based on the observation that Arabidopsis Thaliana Extract and Rhodomyrtus tomentosa Fruit Extract behave synergistically on different models of stress- induced skin damage, in particular skin damage caused by sustained excess levels of cortisol and / or adrenalin (epinephrin).

[0022] The present invention is also based on the observation that Micrococcus Lysate and Rhodomyrtus tomentosa Fruit Extract can synergistically repair cyclobutane-pyrimidine dimers (CPD) helix-distorting DNA damage caused in particular by UV (e.g. UV-B) light exposure.

[0023] Synergy is demonstrated for example if the combined effect of a given amount of each of the two agents together is greater than the weighted average of the effect of the same amounts of each of the two agents individually. The weighted average is calculated as follows: [Math 1]wherein wirepresent the weight of component Xi. For example, in Figure 1 where the two components were tested at the same amount (0.1%), wiis equal 1 for both of them.

[0024] Accordingly, the present invention discloses 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 ageing.

[0025] The present invention also discloses 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 to repair damage to the skin caused by psychological stress in a human or animal patient. Oxoguanine glycosylase-1 and Rhodomyrtus tomentosa Fruit Extract may administered simultaneously or separately; in particular, oxoguanine glycosylase-1 may be administered simultaneously, before or after Rhodomyrtus tomentosa Fruit Extract.

[0026] The present invention also discloses cosmetically or dermatologically effective, in particular synergistic amounts of endonuclease and Rhodomyrtus tomentosa Fruit Extract to repair cyclobutane pyrimidine dimers (CPD) helix-distorting DNA damage caused by UVB exposure.

[0027] Stress is the organism’s response to a psychological, physiological or biological stressor such as a threat, challenge or barrier. During a stressful situation the body induces the adrenal gland to produce two stress hormones, adrenaline and cortisol so that their levels increase from the basal or resting levels to reactive levels. Under normal conditions cortisol levels drop back to basal levels within 20 to 60 minutes. If cortisol levels remain high for longer periods of time, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 months, stress becomes chronic. Under stress conditions cortisol levels may increase to 2 to 20 times the basal level, for example 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 times the basal level.

[0028] The same considerations apply to adrenaline.

[0029] Sustained levels of cortisol and / or epinephrin can cause DNA damage as measured using the Comet Assay, with damage revealed by enzymatic treatment with FPG (Formamidopyrimidine [fapy]-DNA glycosylase).

[0030] Cyclobutane-pyrimidine dimers (CPD) formation caused by UV (in particular UV-B) exposure independently causes helix-distorting DNA damage, which can also be revealed with the Comet Assay.

[0031] The Comet Assay (single-cell gel electrophoresis) is a simple method for measuring deoxyribonucleic acid (DNA) strand breaks in eukaryotic cells. Cells embedded in agarose on a microscope slide are lysed with detergent and high salt to form nucleoids containing supercoiled loops of DNA linked to the nuclear matrix. Electrophoresis at high pH results in structures resembling comets, observed by fluorescence microscopy; the intensity of the comet tail relative to the head reflects the number of DNA breaks.

[0032] 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 .

[0033] Each of oxoguanine glycosylase-1 or endonuclease and Rhodomyrtus tomentosa Fruit Extract can be present in a dermatologically or cosmetically effective amount in a range from 0.00001% to 10%, typically from 0.0001% to 1%, more typically from 0.0005 to 0.5% or from 0.001% to 0.01% or 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 need not be the same, and each of the values above is disclosed separately for oxoguanine glycosylase-1, endonuclease and Rhodomyrtus tomentosa Fruit Extract. The appropriate cosmetically or dermatologically effective, in particular synergistic amounts of each of oxoguanine glycosylase-1, endonuclease and Rhodomyrtus tomentosa Fruit Extract can be determined by the skilled person by means known in the art of cosmetic and dermatologic formulation. The amounts can also be determined for each patient based on the individual characteristics and condition.

[0034] A composition according to the present invention is preferably for topical administration. When the cosmetic composition is a topical formulation it may be a O / W emulsion, W / O emulsion, micro- or multiple emulsions such as a creams, a lotion, a gel, a serum, a spray, a masks, a cleanser, a micellar waters, a self-tan product, an oil (one or multiple phases), a sun protection product, all typical face and body care treatments a solution, an ointment, a paste, an aerosol foam, a powder, a solid or a transdermal patch.

[0035] A cosmetic composition according to the present invention comprises oxoguanine glycosylase-1 or endonuclease and Rhodomyrtus tomentosa Fruit Extract (hereafter also identified as API), as well as any formulation additive known in the art of dermatological or topic cosmetic composition formulation.

[0036] The active agent in the Arabidopsis Thaliana Extract is considered to be 8-oxoguanine glycosylase-1 and the active agent in the Micrococcus lysate is considered to be an endonuclease. Therefore, in the present application these terms are used interchangeably: use of the expression Arabidopsis Thaliana Extract does not preclude the use of 8-oxoguanine glycosylase-1 from other sources, and use of the expression Micrococcus lysate does not preclude the use of the same endonuclease from other sources.

[0037] Excipients for use in topical formulations are well-known in the art and examples may be found in the Handbook of Pharmaceutical Excipients (Rowe, R. C. et al., APhA Publications; 5th ed., 2005). Classes of excipients may include waxes, emollients, thickening agents / viscosity increasing agents, humectants, pH modifiers, water repelling agents, anti- foaming agents, surfactants, solubilizers, wetting agents, penetration enhancers, antioxidants, and solvents. The excipients may also be present in the topical composition at any suitable concentration. In some embodiments, the topical composition includes excipients at a concentration in a range from 70 to 99.99 weight percent.

[0038] The carrier of the cosmetic composition can be a clay or a liposome. Examples of suitable clays can include bentonite, hectorite, stearalkonium hectorite & 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.

[0039] 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 been proven to enhance drug solubility and controlled distribution, as well as their capacity for surface modifications for targeted delivery into skin, prolonged, and sustained release. Based on the composition, liposomes can be considered to have evolved from conventional, long-circulating, targeted, and immune-liposomes to stimuli-responsive and actively targeted liposomes. Many liposomal-based drug delivery systems are currently clinically approved to treat several diseases, such as cancer, fungal and viral infections; more liposomes have reached advanced phases in clinical trials. According to the liposomes structures, they are classified into four categories based on size and number of bilayers: small unilamellar vesicles (SUV), large unilamellar vesicles (LUV), multilamellar vesicle (MLV), and multivesicular vesicles (MVV). Liposomes have mono phospholipid bilayer in a unilamellar structure, while they have an onion-like structure in a multilamellar structure. MVV form a multilamellar arrangement with concentric phospholipid spheres as many unilamellar vesicles are produced within largerliposomes. The size of the vesicles is an important factor that controls the circulation half-life of liposomes. Both the size and number of bilayers influence the amount of the encapsulated drug. Liposomes interaction with the cell membrane is represented by various theories: specific (modified with receptor-mediated) or nonspecific endocytosis, local fusion (adhesion), phagocytosis, and absorption into the cell membrane. Liposome-cell interactions are influenced by a variety of factors, including composition, the diameters of liposomes, surface charge, targeting ligand on the liposome surface, and biological environment.

[0040] An example of liposome useful in the context of the present invention is disclosed in EP 2163236, in particular Example 1, whose specific content is included herein by reference. The base composition can in particular comprise shell liposomes with a particle size of 250-600 nm having a viscosity in a hydrogel of between 4.000 and 20.000 nPa*s, and which comprise in their water phase at least two internal liposomes, each of which comprises a different one of the active agents of the invention, whereby the internal liposomes have a particle size of between 50 and 200 nm.

[0041] Relative to the total concentration of the cosmetic composition, the carrier is in a range of from about 0.01 wt% to about 70wt%, about 20 wt% to about 50 wt%, 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 wt%.

[0042] A further example of liposomes are cationic liposomes. Cationic liposomes are liposomes displaying a positive charge on their outer surface, which is composed as known in the art. Typical micro-vesicles are composed of phospholipids, especially sphingomyelin, phosphatidylcholine and / or cholesterol, but may also include other lipids such as those found in eggs and phosphatidylcholine as long as they are compatible with the bilayer structure.

[0043] The membrane bilayer may comprise or be coated with cationic lipids to impart the positive charge onto the outer surface of the micro-vesicle. 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, domiphen bromide, tricetylmonium chloride, distearyldimonium chloride and hydroxypropylbisstearyldimonium chloride. Preferred lipids are cetylpyridinium chloride, benzalkonium chloride, distearyldimonium chloride or didecyldimonium chloride.

[0044] The membrane bilayer may comprise other optional components such as bulking agents like 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.

[0045] The positively charged micro-vesicles can be used as such for the delivery of the synergistic compositions according to the present invention to cells, in particular to skin cells.

[0046] Alternatively, they can be used to prepare exosome-like vectors. In particular, the positive charge on the surface of the liposomes can be used to functionalize the micro- vesicles through electrostatic interactions with appropriate ligands. These ligands have the function of facilitating cell-to-cell communication and material transfer, in particular in skin cells.

[0047] Particularly effective ligands belong to the class of oligopeptides and polypeptides that 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.

[0048] The texture agent (emollient) can include a mixture of dicaprylyl carbonate & tocopherol, a mixture of caprylic / capric triglyceride, a mixture of caprylic / capric triglyceride & 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 oil, vegetable oil, avocado oil, canola oil, corn oil, soy bean oil, sunflower oil, safflower oil, meadowfoam seed oil, bilberry sead oil, watermelon seed oil, olive oil, cranberry, macadamia nut oil, argan oil, pomegranate oil, argan moraccan oil, blue berry oil, raspberry oil, walnut oil, pecan oil, peanut oil, bayberry oil, mango seed oil, Manila oil, castor oil:Shea butter, jojoba oil, hydrolyzed jojoba oil, Carnauba butter, Carnauba wax, castor isostearate succinate stearyl heptanoate, cetyl ricinoleate, oleyl frucate, sucrose monostearate, sucrose distearate, sucrose tristearate, sucrose tetrastearate, candela wax, soybean wax, Rapeseed wax, palm wax, bees wax, 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, lower molecular weight polypropylene waxes, PEG-30 glyceryl cocoate, PEG-80 Glyceryl cocoate, Glyceryl stearate, PEG-8 Ricinoleate, PEG-8 Raspberriate, Linear (otherwise known as bis) and Pendent versions of including hydroxyl terminated and methyl ether terminated; PEG- 3 to PEG-32 Dimethicone (including but not limited to: PEG-3 Dimethicone, Dimethicone, PEG-9 Dimethicone, PEG-10 Dimethicone, PEG-11 Methyl ether dimethicone, PEG-12 Dimethicone, PEG-14 Dimethicone, PEG-17 Dimethicone, PEG-Dimethicone), bis-PEG / PPG-20 / 20 Dimethicone, PEG / PPG 20 / 23 Dimethicone, PEG / PPG 20 / 22 Butyl Ether Dimethicone, PEG / PPG 23 / 6 Dimethicone, PEG / PPG 20 / 15 Dimethicone. Alkyl modified dimethicone (stearoxy dimethicone, behenoxy dimethicone,cetyl dimethicone, certeryl methicone C30-45 Alkyl cetearyl dimethicone copolymer, Alkyl dimethicone, caprylyl methicone, PEG-8 dimethicone / dimer dilinoleic acid copolymer, Bis-PEG-10 Dimethicone / Dimer Dilinole ate Copolymer, Stearoxymethicone / Dimethicone Copolymer, Dipheyl dimethicone, Lauryl polyglycerol-3 polydimethylsiloxyethyl dimethicone, Lauryl PEG-9 polydimethylsiloxyethyl dimethicone), Dimethicone fluid (>20cst), quatemized ammonia silicone polymers, Amino silicones, silicone quatemium-18, Amodimethicone, phenyltrimethicone, amino silicone polyethers, Polyglycerol-3 Disiloxane dimethicone, Polyglycerol-3 polydimethylsiloxyethyl dimethicone, silica dimethyl silylate, bambusa arundinacea, and PEG-9 polydimethylsiloxyethyl dimethicone.

[0049] Relative to the total concentration of the cosmetic composition, the texture agent is in a range of from about 10 wt% to about 60 wt%, about 20 wt% to about 40 wt%, less than, equal to, or greater than about 10 wt%, 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 wt%.

[0050] Antioxidants slow, protect against, and help repair the adverse effects of oxidative degradation. The antioxidant can include a mixture of diethylhexyl syringyllidenemalonate & caprylic / capric triglyceride, or a combination thereof. Other antioxidants include vitamin C and its derivates, niacinamide, resveratrol, vitamin E and its derivates, retinol and its derivates, coenzyme Q10, and polyphenols and diethylhexylsyringilidenemalonate. Relative to the total concentration of the cosmetic composition, the antioxidant is in a range of from about 0.05 wt% to about 20 wt%, about 5 wt% to about 15 wt%, less than, equal to, or greater than about 2 wt%, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or about 20 wt%

[0051] 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 blends thereof. In particular examples, the humectant includes an alkylene glycol, such as hexylene glycol.

[0052] In some embodiments, the topical compositions include at least one oil. Suitable oils include silicones (such as dimethicone), hydrocarbons, esters, amides, ethers, and mixtures thereof.

[0053] The disclosed compositions can comprise one or more of the following cosmetic products as an additives: acetyl hexapeptide-3 (argirilene), acrylates / C10-30 alkyl acrylate cross-polymer, 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, argirilene, 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 (hemp) seed oil, caprylic / capric triglyceride, Carica papaya (papaya) seed oil, cellulose gum, Centella asiatica (gotu kola) 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 paradisi (grapefruit) essential oil, Cocos nucifera (coconut) oil, coenzyme Q10, Crithmum maritimum (sea fennel) extract, decyl polyglucoside, dipeptide diaminobutyroyl benzylamide diacetate (snake peptides), elastin, Enteromorpha compressa extract, fatty acids, gamma-oryzanol, geranylgeranone gga, gluconolactone, glucosamine, glycan booster, tetradecyl amino-butyroylvalyl-aminobutyric urea trifluoro-acetate, 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, homeostatine, hyaluronic acid, hydrolyzed rice bran extract, hydroquinone, lactoceramides, Lavendula angustfolia (lavender) essential oil, lecithin, Leontopodium alpinum (edelweiss) extract, linoleic acid, magnesium ascorbyl phosphate, magnesium chloride, matrix peptides, mixed tocopherols (vitamin E), Morus alba (mulberry) root extract, niacinamide, noni, non-nano zinc oxide, oat beta glucans, Oenothera biennis (evening primrose) oil, 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, Pinusdensiflora (red pine needle) oil, Plantago species (plantain) leaf extract, Polianthes tuberosa (tuberose) essential oil, polyaminopropyl biguanide (cosmocil CQ), polyglucose / lactylate, Populus tremuloides (aspen) bark extract, potassium sorbate, Prunus armeniaca (apricot) kernel oil, pullulan, red pond 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 (red raspberry) seed oil, saccharomyces ferment, Salvia hispanica (chia) seed oil, Sclerocarya birrea (marula) oil, sea 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, undecylenoyl phenylalanine, vitamin A, vitamin C, Vitus vinifera (grapeseed) oil, watermelon seed oil, white tea extract, xanthan gum, and xylitum black tea ferment (kombucha) extract. In particular the additive can be Creatine and / or bifida ferment lysate.

[0054] A composition according to the invention may additionally comprise a UV filter. According to various aspects of the present disclosure, the one or more UV filters comprise a UV-A filter, a UV-B filter, a UV-A + UV-B broadband filter, or a mixture thereof. In certain aspects, the UV-A filter is chosen from: - Butyl methoxydibenzoylmethane or l-(4-tert-Butylphenyl)-3-(4-methoxyphenyl) propane- 1, 3 -dione, - Terephthalylidene dicamphor sulphonic acid or 3,3'-(l,4-Phenylenedimethylene) bis (7,7-dimethyl-2-oxobicyclo-[2.2.1] hept-l-ylmethanesulfonic acid) and its salts, - Menthyl Anthranilate, - Bisdisulizole Disodium or di sodium phenyl dibenzimidazole tetrasulfonate, - Diethylamino Hydroxybenzoyl Hexyl Benzoate, and - Dimethoxyphenyl-[l-(3,4)]-4, 4-dimethyl 1,3-pentanedione.

[0055] In certain aspects, the UV-A filter is butyl methoxydibenzoylmethane. In certain aspects, the three UV-B filters are independently chosen 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 Benzoic acid, 4,4-{[6-[[[(l,l- dimethylethyl)amino]carbonyl]phenyl]amino]-l,3-5-triazine-2,4-diyl]diimino}bis-, bis(2-ethylhexyl)ester, - Digalloyl trioleate, - Diisopropyl methyl cinnamate, - Ethyl dihydroxypropyl PABA, - Ethylhexyl dimethoxy benzylidene dioxoimidazoline 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)-l,3,5-triazine, - Ferulic acid, Glyceryl ethylhexanoate dimethoxycinnamate, - Glyceryl PABA, - Benzoic acid, 2-hydroxy-, 3,3,5-trimethylcyclohexyl ester, - Isoamyl p-methoxycinnamate or Isopentyl-4-methoxycinnamate, - Isopentyl trimethoxycinnamate trisiloxane, - Isopropyl benzyl salicylate, - Isopropyl methoxycinnamate, - Lawsone + dihydoxyacetone, - 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-sulphonic acid and its potassium, sodium and triethanolamine salts, - Polyacrylamido methylbenzylidene camphor, poly silicone- 15 or Dimethicodiethylbenzalmalonate, - Salicylic acid, and - TEA salicylate (Trolamine Salicylate). In certain aspects, the broad band UV-A and UV-B filter is chosen 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)-l,3,5-triazine-2,4-diyl)bis(5-((2-ethylhexyl)oxy)phenol), - 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.

[0056] In certain aspects, each of the UV filters in the sunscreen composition is present in an amount of from 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%, about 0.1 wt% to about 10 wt%, 0.1 wt%to about 8 wt%, about 0.1 wt% to about 6 wt%, wherein the weight percent is based on the total weight of the sunscreen composition.

[0057] In certain aspects, the sunscreen composition comprises less than about 35 wt% UV filters. In certain aspects, the sunscreen composition comprises between about 5 wt% and about 25 wt% UV filters. In certain aspects, the sunscreen composition comprises about 20 wt% UV filters.

[0058] In some embodiments of the invention, the topical compositions may have a viscosity increasing agent concentration in a range from 0.5 to 30% by weight, a solvent concentration in a range from 50 to 90% by weight, and a humectant concentration in a range from 2 to 20% by weight.

[0059] In some embodiments, synergistic compositions according to the present invention further comprising at least 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 fragrances.

[0060] The hormonal damage can be one of acne, eczema, psoriasis, rosacea, rashes, hives.

[0061] The compositions according to the invention can be used for the treatment, reduction, and / or prevention of skin hormonal damage or signs of skin ageing, in particular where these are one or more of acne, eczema, psoriasis, rosacea, rashes, hives, fine lines or wrinkles; reduction of skin pore size; improvement in skin thickness, plumpness, and / or tautness; improvement in skin smoothness, suppleness and / or softness; improvement in skin tone, radiance, and / or clarity; improvement in procollagen, and / or collagen production; improvement in maintenance and remodeling of elastin; improvement in skin texture and / or promotion of retexturization; improvement in skin barrier repair and / or function; improvement in appearance of skin contours; restoration of skin luster and / or brightness; replenishment of essential nutrients and / or constituents in the skin; improvement of skin appearance decreased by aging and / or menopause; improvement in skin moisturization; increase in skin elasticity and / or resiliency; treatment, reduction, and / or prevention of skin sagging; improvement in skin firmness; reduction of pigment spots and / or mottled skin; and improvement of optical properties of skin by light diffraction or reflection. EXAMPLES

[0062] 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

[0063] Normal human keratinocytes were treated with cortisol solution at 5µM during 24h. Cortisol was then removed, and cells were treated with the composition during 5min, 10min, 20min, 30min. DNA damage were assessed by using the Comet Assay, with oxidative damage revealed by enzymatic treatment with FPG (Formamidopyrimidine [fapy]-DNA glycosylase). DNA damage was expressed as the Chi-2 Olive Tail Moment (Chi² OTM). Example 2

[0064] Exemplary composition 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 to 100

Claims

CLAIMS What is claimed is:

1. A cosmetically or dermatologically effective amount of 8 oxoguanine glycosylase-1 or endonuclease and of Rhodomyrtus tomentosa Fruit Extract for reducing one or more signs of ageing.

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 to repair damage to the skin caused by psychological stress in a human or animal patient.

3. A cosmetically or dermatologically effective amount of endonuclease and Rhodomyrtus tomentosa Fruit Extract to repair cyclobutane pyrimidine dimers (CPD) helix-distorting DNA damage caused by UVB exposure.

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

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

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

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

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

9. A cosmetically or dermatologically effective amount according to any of the claims 7 or 8, wherein the sign of ageing or the hormonal damage is one of acne, eczema, psoriasis, rosacea, rashes, hives, fine lines or wrinkles; reduction of skin pore size; improvement in skin thickness, plumpness, and / or tautness; improvement in skin smoothness, suppleness and / or softness; improvement in skin tone, radiance, and / or clarity; improvement in procollagen, and / or collagen production; improvement in maintenance and remodeling of elastin; improvement in skin texture and / or promotion of retexturization; improvement in skin barrier repair and / or function; improvement in appearance of skin contours; restoration of skin luster and / or brightness; replenishment of essential nutrients and / or constituents in the skin; improvement of skin appearance decreased by aging and / or menopause; improvement in skin moisturization; increase in skin elasticity and / or resiliency; treatment, reduction, and / or prevention of skin sagging; improvement in skin firmness; reduction of pigment spots and / or mottled skin; and improvement of optical properties of skin by light diffraction or reflection.

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

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

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

13. The composition according to any 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 fragrances.

14. Composition according to any of claims 10 to13, wherein the amount of each of 8- oxoguanine glycosylase, endonuclease and Rhodomyrtus tomentosa Fruit Extract is comprised in the range of 0.00001% to 10% based on the total weight of the composition.

15. Composition according to any of claims 10 to14 further comprising bifida ferment lysate and / or creatine.

16. Composition according to any of claims 10-15, further comprising lecithin.

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

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

19. Composition according to any of claims 10 to 18, wherein 8 oxoguanine glycosylase-1 or endonuclease and Rhodomyrtus tomentosa Fruit Extract are present in synergistic amounts.

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

21. Dermatological or cosmetic method of treating hormonal skin damage, repair damage to the skin caused by psychological stress and or sign of ageing is caused by DNA helix distortion induced by cyclobutane pyrimidine dimers (CPD) formation comprising administering to the patient a synergistic amount of 8 oxoguanine glycosylase-1 or endonuclease and Rhodomyrtus tomentosa Fruit Extract.

22. Amount according to any of claims 1 to 9 or composition according to any of claims 10-19, wherein the 8-oxoguanine glycosylase is present as an extract of Arabidopsis thaliana.

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