Compositions containing Epilobium fleischeri extract for treating signs of aging

Abstract

The present invention relates to the (cosmetic) use of an extract of Epilobium fleischeri for treating the signs of skin ageing.

Description

Detailed Description of the Invention

[0001] The present invention relates to the (cosmetic) use of an extract of Epilobium fleischeri for treating the signs of skin ageing.

[0002] Life expectancy continues to increase in many countries around the world. Therefore, there is an ever-increasing demand for treatments that counteract or reverse the aging process, not only to combat age-related diseases but also to address the physical signs of aging. It is therefore not surprising that the need for cosmetic products that can be applied topically to the skin to combat the signs of skin aging, such as wrinkles and age spots, has increased significantly in recent years.

[0003] Skin aging is a complex process. Intrinsic aging is an inevitable physiological process that results in thin, dry skin, fine lines, loss of elasticity, abnormal pigmentation, gray hair, and hair loss. Extrinsic aging is caused by external environmental factors, particularly sunlight and air pollution, and results in coarse wrinkles, loss of elasticity, sagging, and a rough appearance. Other factors that may further contribute to an aged appearance include general poor health, unhealthy diet, smoking, and alcohol.

[0004] It is now well established that cellular senescence plays a crucial role in the aging process. Cellular senescence is a physiological process characterized by permanent and irreversible cell cycle arrest and the acquisition of a proinflammatory and proteolytic secretome, resulting in a tumor-suppressive cell fate. Senescent cells grow to a large size and cease replicating. In addition, senescent cells produce a potent mixture of molecules known as senescence-associated secretory phenomena (SASP), which stimulate the immune system into an inflammatory state, disrupt tissue structure and function, and ultimately promote the senescence of neighboring cells. SASP is one of the key features that distinguish senescent cells from quiescent, terminally differentiated, and other types of non-proliferating cells.

[0005] Intrinsic aging is typically correlated with an increase in senescent cells, including senescent skin cells. For example, senescence of dermal fibroblasts is considered an important driver of senescence-associated phenotypes in the skin. Therefore, there is a continuing need to discover agents that can selectively eliminate these deviant cells.

[0006] Senolytic agents are typically understood as agents capable of selectively eliminating senescent cells and were the first potential anti-aging therapy successfully tested in preclinical in vivo models. In other words, if the activity of a drug involves specifically inducing or promoting cell death, particularly apoptotic cell death, of senescent cells in the corresponding tissue, the drug is considered to have senolytic activity. Currently, several senolytic agents, such as navitoclax, have been identified. These agents can ultimately selectively eliminate senescent cells by inducing the apoptotic process, which does not occur in non-senescent or normal cells, leaving them unaffected.

[0007] Disadvantages of currently known senolytic agents are that they are often of synthetic origin, have rather complex chemical structures that require significant effort to obtain, exhibit low solubility in conventional cosmetic oils, and / or may have severe undesirable side effects.

[0008] Therefore, there is a continuing need for naturally derived senolytic agents that have reduced undesirable side effects and are economically available.

[0009] Surprisingly, it has now been found that an extract of Epilobium fleischeri exhibits senolytic activity in human dermal fibroblasts and can thereby be used to treat the signs of skin ageing.

[0010] Thus, in a first embodiment, the present invention relates to the cosmetic use of an extract of Epilobium fleischeri as an active ingredient for the prevention, reduction or treatment of signs of skin ageing.

[0011] In another embodiment, the present invention also provides the use of an extract of Epilobium fleischeri as an active ingredient in and for the manufacture of a topical composition for treating signs of skin aging.

[0012] In a further embodiment, the present invention also provides an extract of Epilobium fleischeri as an active ingredient for use in selectively eliminating senescent skin cells.

[0013] The present invention also provides the use of an extract of Epilobium fleischeri as an active ingredient in, and for the manufacture of, a topical composition for selectively eliminating aging skin cells.

[0014] The present invention also provides a cosmetic method for treating signs of skin aging, comprising topically applying to the external surface of the human body a topical composition containing an extract of Epilobium fleischeri.

[0015] The present invention also refers to a cosmetic skin and scalp care method for selectively removing senescent skin cells, preferably senescent human dermal fibroblasts, by applying at least an effective amount of an extract of Epilobium fleischeri extract; or a composition comprising at least said extract, to the skin or scalp in need thereof.

[0016] As used herein, the term "cosmetic" refers to treatments that do not cure, treat, or prevent a disease or disorder, but instead function as skin care products intended to beautify or improve the appearance of the skin, e.g., skin color or texture.

[0017] In the context of the present invention, the term "treat" means to reduce, prevent, or eliminate.

[0018] As used herein, the term "skin aging signs" refers to one or more characteristics of intrinsic or chronological aging, such as thin skin, fine wrinkles, loss of elasticity, and abnormal pigmentation. These signs affect everyone, regardless of skin type or health condition. As mentioned above, this process can be enhanced by extrinsic factors, such as exposure to sunlight, pollutants, and cigarette smoke.

[0019] Thus, the term "treating the signs of skin aging" includes, but is not limited to, the prevention, reduction or treatment of fine lines, wrinkles, crow's feet, sagging skin, thinning skin, age spots, as well as improving skin elasticity or skin firmness.

[0020] The term "preventing, reducing or treating skin aging" also includes smoothing and reducing the amount and depth of wrinkles and fine lines in those in need thereof.

[0021] As used herein, the term "external surface of the human body" includes the skin and scalp (including hair and axillae). Preferably, in all embodiments of the present invention, the external surface of the human body treated in accordance with the present invention is the skin of the face, neck and / or body, most preferably the face (including the (lateral) cheeks, forehead, nose, chin).

[0022] As used herein, the term "skin cells" may refer to any skin-resident cell type (such as dermal fibroblasts, melanocytes, hair follicle dermal papilla cells, and epidermal keratinocytes), or to cell types derived from the skin appendages (such as sebocytes), or mixtures thereof. Preferably, in all embodiments of the present invention, the term refers to (human) dermal fibroblasts.

[0023] In the context of the present invention, the term "senescence" refers to a state of permanent cell cycle arrest in which cells remain metabolically active and adopt characteristic phenotypic changes. Establishment of this phenotype is thought to be either the result of telomere shortening after several cell divisions (replicative senescence) or a response to stress stimuli (stress-induced senescence). One of the defining characteristics of senescent cells is their stable cell cycle arrest. This cell cycle exit is mediated by the downregulation of p53 / p21 and p16 INK4a Senescent cells are regulated by activating the β / Rb tumor suppressor pathway. Unlike quiescent cells, senescent cells do not respond to mitogen or growth factor stimulation and are therefore unable to re-enter the cell cycle, even under favorable growth conditions. Senescent cells also differ from terminally differentiated cells, which irreversibly withdraw from the cell cycle. Whereas terminal differentiation is the result of a defined developmental program that converts undifferentiated progenitor cells into specialized effector cells, senescence is primarily realized as a cellular stress response.

[0024] Senescent cells can be clearly identified in vitro and in vivo because they exhibit a number of characteristics that allow them to be clearly identified.

[0025] For example, senescent cells often become multinucleated, appear larger and elongated, and exhibit spindle-shaped and vacuolated features. Senescent cells also exhibit changes in chromatin organization that can help identify them. While DNA staining reveals perfectly uniform color contours in normal cells, senescent cells typically exhibit a punctate pattern known as senescence-associated heterochromatin formation (SAHF). This phenomenon is due to intensive remodeling of chromatin, which results in its resistance to digestion by nucleases.

[0026] Furthermore, senescence-associated chromatin remodeling leads to significant transcriptional changes. Among the upregulated gene combinations are a key subset of genes encoding secreted proteins, including cytokines and chemokines with pro-inflammatory properties, as well as various growth factors and proteases that alter both tissue structure and function, collectively known as the SASP. The SASP is one of the key features that distinguish senescent cells from quiescent, terminally differentiated, and other types of non-proliferating cells.

[0027] A distinctive measurable characteristic of senescent cells is the presence of β-galactosidase enzyme activity. This enzyme is normally active at pH 4.0 in lysosomes, but in senescent cells it is active even at pH 6.0. This phenomenon, termed senescence-associated β-galactosidase (SA-β-gal) activity, is thought to result from the enlargement of lysosomal structures in senescent cells. SA-β-gal activity can be detected by histochemical staining using X-gal as a substrate for SA-β-gal. SA-β-gal activity is detected in most senescent conditions both in vitro and in vivo and is therefore considered a de facto hallmark of senescence. SA-β-gal can be visualized intracellularly to quantify the level of senescence using flow cytometry.

[0028] As used herein, the term "senolytic activity" refers to specifically (and selectively) inducing or promoting cell death of senescent cells. Senolytic activity may also be considered to be the ability to selectively eliminate senescent cells, for example, by inducing or promoting apoptosis. It may also be the ability to selectively eliminate senescent cells found in a tissue with reduced or no deleterious effects on normal resident (i.e., non-senescent) cells of said tissue. Such senolytic properties may be beneficial, for example, in preventing or attenuating the increase in the number of senescence-associated senescent cells and / or stress-associated senescent cells in a tissue.

[0029] The selective elimination of senescent cells can be determined by the change in the ratio of senescent cells (increase) to proliferating cells (decrease) based on the SA-β-gal activity of a cell population model after incubation with a fixed concentration of a test compound in a suitable medium, as exemplified in the Examples. Such a cell population model can contain a set percentage ratio of senescent cells to proliferating cells. Senescent cell elimination activity can be evaluated by comparing the condition with and without the addition of a test compound.

[0030] A compound can be determined to be capable of selectively eliminating senescent cells if the calculated proportion of senescent cells (based on SA-β-gal activity) is statistically significantly reduced relative to the control (no compound added during incubation).

[0031] Preferably, in one embodiment, the (total) number of senescent cells is reduced by at least 20%, more preferably at least 25%, most preferably at least 30%, e.g., at least 40%, relative to the initial number of senescent cells present in the treated sample, such as skin tissue, while it is well understood that the number of normal cells is increased by the same factor.

[0032] Preferably, in another embodiment, the number of senescent cells is reduced by at least a statistically significant difference in percentage between the control and treated conditions, more preferably by at least a 50% difference (half of the original senescent cells are removed), and most preferably by at least a 90% difference, relative to the initial number of senescent cells present, while it is well understood that the number of normal cells is increased by the same factor.

[0033] As used herein, the term "extract" may be understood in the broadest sense generally understood in the art. The extract may be any substance obtained by extracting a part of the raw material (herein, the flowers, leaves, seeds, and / or stems of Epilobium fleischeri).

[0034] In a preferred embodiment, the Epilobium fleischeri extract has senolytic activity, which involves specifically inducing or promoting cell death of senescent cells in tissues, preferably apoptotic cell death.

[0035] Thus, the Epilobium fleischeri extract according to the present invention can be obtained by any means known to those skilled in the art. The Epilobium fleischeri extract may optionally be obtained from a commercial supplier or may be prepared partially or completely from the Epilobium fleischeri plant or one or more parts thereof.

[0036] The extract can be any type of extract. The extract can be prepared from fresh flowers, leaves, seeds, and / or stems of Epilobium fleischeri, or from dried flowers, leaves, seeds, and / or stems of Epilobium fleischeri, or from frozen or freeze-dried flowers, leaves, seeds, and / or stems of Epilobium fleischeri. Preferably, in all embodiments of the present invention, the extract is derived from flowers and leaves or flowers, leaves, and stems of Epilobium fleischeri. Preferably, in all embodiments, the Epilobium fleischeri extract is derived from flowers, leaves, and stems.

[0037] Preferably, the flowers, leaves, seeds and / or stems of Epilobium fleischeri may be used in chopped, blended or crushed form. In a preferred embodiment, the extract is prepared from dried flowers, leaves and / or stems of Epilobium fleischeri, in particular from dried and crushed flowers, leaves and / or stems of Epilobium fleischeri.

[0038] Typically, extraction is achieved by using a solvent. Thus, in a preferred embodiment, the extract according to the present invention is obtained by solvent extraction methods, including low-temperature or high-temperature extraction, ultrasonic extraction, reflux cooling, needle extraction, and microwave extraction. In a preferred embodiment, the extract is obtained by ultrasonic extraction.

[0039] One or more solvents may be used for extraction. Such solvents may be any solvent suitable for this purpose. Typically, the solvent is liquid under the conditions used for extraction. The solvent may be selected from the group consisting of organic solvents (e.g., alcohols (e.g., methanol, ethanol, propanol, butanol, pentanol, phenol, glycerol, 1,3-butylene glycol, propanediol, etc.), water (including hot water or subcritical water), aqueous buffer solutions, and combinations of two or more thereof. The organic solvent may be aliphatic or aromatic. Preferably, the solvent may be hydrated.

[0040] In this specification, a solvent may be added to the flowers, leaves, seeds, and / or stems of Epilobium fleischeri and allowed to stand for a certain period of time. In a further step, the solid portion is preferably separated by primary extraction. This separation may be achieved by any means, such as filtration, sieving, ultrafiltration, cross-flow filtration, centrifugation, sedimentation over time, or a combination of two or more thereof.

[0041] Preferably, in all embodiments of the present invention, the Epilobium fleischeri extract used according to the present invention is prepared by extraction with a polar solvent such as water, ethanol, glycerin, glycol or mixtures thereof, preferably ethanol or water as well as mixtures thereof.

[0042] In all embodiments of the present invention, it is preferred to extract the flowers, leaves, seeds and / or stems of Epilobium fleischeri with an ethanol / water mixture containing 10-90% (m / m) ethanol, or containing 25-85% (m / m) ethanol, or containing 40-75% (m / m) ethanol, or containing 50-70% (m / m) ethanol, or containing 50-60% (m / m) ethanol.

[0043] In all embodiments of the present invention, the extraction is advantageously carried out at a temperature in the range of 10 to 150° C., or 15 to 100° C., or 20 to 80° C., or 20 to 70° C., or 20 to 60° C., or about 20° C. In a preferred embodiment, the extraction is carried out at a temperature selected in the range of ambient temperature (i.e. 15 to 25° C., in particular about 20° C.) to 60° C.

[0044] In all embodiments of the present invention, the extraction is preferably carried out at a temperature selected in the range of about 20°C (room temperature) to 60°C and at ambient pressure (i.e., 980-1200 mbar) for 1-3 hours.

[0045] In all embodiments of the present invention, the Epilobium fleischeri extract can be either a liquid extract, such as an aqueous extract, or a dry extract.

[0046] As used herein, the term "dry extract" can be understood in the broadest sense as the extract according to the present invention as a dry substance, i.e., an extraction product without solvent. The dry extract can optionally be physically present as a dry substance. However, in the calculation of percentages referring to dry substance, it will be directly understood that the dry extract does not necessarily have to be a dry substance present in physical form, but can also be present in dissolved form. Then, in the calculation, the mass of the solvent is numerically subtracted from the total mass.

[0047] A dry substance (in physical form) can be obtained by a suitable extraction method, followed by a step of drying the resulting extract. Drying can be carried out by any method known in the art that is suitable for this purpose. Drying refers to the removal of one or more solvents used in the extraction. Removal of one or more solvents can be carried out by any means. For example, it can be achieved by exposing the extract to a dry atmosphere at high temperature and / or by placing the extract on a heated plate to evaporate the solvent. For example, drying can be achieved by evaporation in vacuum and / or at high temperature (e.g., in a rotary (vacuum) evaporator), or by crystallizing the solid material of interest. Alternatively, or additionally, drying can be achieved by atomization or by freeze-drying.

[0048] Preferably, in all embodiments of the present invention, the Epilobium fleischeri extract is an aqueous or dry (physical form) extract. The aqueous Epilobium fleischeri extract is preferably prepared by a process comprising the steps of crushing the aerial parts of Epilobium fleischeri, such as flowers, leaves and stems, which have preferably been previously dried, more preferably dried with hot air, followed by extraction of the dried plant with a solvent, preferably an ethanol / water mixture, having all the definitions and preferences as indicated herein, followed by removal of the ethanol, for example by (vacuum) distillation, to obtain an aqueous Epilobium fleischeri extract.

[0049] The dry extract is obtained by vacuum distillation of ethanol and water at a temperature selected preferably in the range of 50-70°C until a dry extract is obtained.

[0050] In all embodiments of the present invention, the aqueous or dry extract of Epilobium fleischeri may be mixed with further ingredients, such as, preferably, water, glycerin, citric acid, and a preservative such as potassium sorbate, before use, for example, for incorporation into a topical composition according to the present invention.

[0051] Preferably, in all embodiments of the present invention, the Epilobium fleischeri extract used in the topical composition as disclosed herein contains (i) 5-10% by weight, based on the dry matter of the Epilobium fleischeri flower, leaf, and stem extract, (ii) 25-50% by weight of water, (iii) less than 50% by weight of a diol, preferably glycerin, and (iv) 0.1-1% by weight of one or more additives, preferably citric acid and / or potassium sorbate, advantageously all components totaling 100% by weight.

[0052] In all embodiments of the present invention, the Epilobium fleischeri extract is preferably administered in the form of a topical composition comprising an effective amount of the Epilobium fleischeri extract and a cosmetically acceptable carrier.

[0053] The term "effective amount" refers to the amount necessary to achieve a desired physiological effect. The physiological effect may be achieved by a single application or by repeated applications. The administered dose may, of course, vary depending on known factors, such as the physiological characteristics of the particular composition containing Epilobium fleischeri extract, its mode and route of administration; the recipient's age, health, and weight; the type of concurrent treatment; the frequency of treatment; and the desired effect, and can be adjusted by one skilled in the art.

[0054] The term "cosmetically acceptable carrier" (also referred to herein as carrier) refers to all vehicles / carriers conventionally used in topical compositions, i.e., which are suitable for topical application to keratinous tissue, have good aesthetic properties, are compatible with the active agents present in the composition, and do not raise any undue safety or toxicity concerns. Such carriers are well known to those skilled in the art and can include one or more compatible liquid or solid filler diluents, excipients, additives, or vehicles suitable for application to the skin.

[0055] Generally, the amount of Epilobium fleischeri extract in the topical composition according to the present invention is selected in the range of 0.001 to 10% by weight, more preferably 0.01 to 8% by weight, even more preferably 0.1 to 7% by weight, even more preferably 0.1 to 5% by weight, and even more preferably 0.1 to 3% by weight, based on the total weight of the topical composition. More preferred ranges are 0.05 to 2% by weight and 0.1 to 1% by weight.

[0056] The exact amount of carrier will depend on the actual levels of Epilobium fleischeri extract and any other optional ingredients (e.g., other active ingredients) that one of ordinary skill in the art would classify as different from a carrier.

[0057] In an advantageous embodiment, the topical composition according to the present invention comprises from about 50% to about 99%, preferably from about 60% to about 98%, more preferably from about 70% to about 98%, for example, in particular from about 80% to about 95%, of a carrier, based on the total weight of the topical composition.

[0058] In a particularly advantageous embodiment, the carrier further comprises at least 40% by weight, more preferably at least 50% by weight, most preferably at least 55% by weight of water, for example, in particular from about 55 to about 90% by weight of water.

[0059] Topical compositions according to the present invention are preferably prepared by mixing an extract of Epilobium fleischeri, having all the definitions and preferences as set forth herein, with / in a cosmetically acceptable carrier.

[0060] The topical composition may contain further ingredients that may form part of the carrier. Such ingredients are, in particular, surfactants, emulsifiers, thickeners, and oils. Suitable such surfactants, emulsifiers, thickeners, and oils are well known to those skilled in the art.

[0061] The topical compositions of the present invention (including the carrier) may contain further conventional (cosmetic) adjuvants and additives, such as preservatives / antioxidants, fatty substances / oils, water, organic solvents, silicones, thickeners, emollients, emulsifiers, antifoaming agents, aesthetic ingredients such as fragrances, surfactants, fillers, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, dyes, colorants / colorants, abrasives, absorbents, chelating and / or sequestrants, essential oils, skin sensates, astringents, pigments or any other ingredient normally incorporated into such compositions.

[0062] According to the present invention, the composition according to the present invention may also contain additional cosmetic active ingredients conventionally used in topical compositions. Exemplary active ingredients include skin lightening agents; UV filters, agents for treating hyperpigmentation; agents for preventing or reducing inflammation; stabilizers, moisturizers, soothing and / or revitalizing agents, and agents for improving elasticity and skin barrier.

[0063] Unless otherwise specified, the excipients, additives, diluents, etc. described below are suitable for compositions according to the invention. The required amounts of cosmetic and dermatological adjuvants and additives can be easily determined by those skilled in the art based on the desired product.

[0064] Additional ingredients can be added to the oily phase, the aqueous phase, or individually as deemed appropriate. The mode of addition can be readily adapted by one skilled in the art.

[0065] Examples of cosmetic excipients, diluents, adjuvants, additives, and active ingredients commonly used in the skin care industry that are suitable for use in the cosmetic compositions of the present invention are described, for example, but not limited to, in the International Cosmetic Ingredient Dictionary & Handbook by the Personal Care Product Council (http: / / www.personalcarecouncil.org / ), accessible via INFO BASE online at http: / / online.personalcarecouncil.org / jsp / Home.jsp.

[0066] Cosmetic active ingredients useful herein may in some cases provide more than one benefit or function by more than one mechanism of action.

[0067] Naturally, the skilled person will carefully select the optional additional components, adjuvants, diluents and additives mentioned above, and / or their amounts, so that the advantageous properties inherently associated with the combination according to the invention are not adversely affected or are not substantially affected by the envisaged addition.

[0068] The topical composition according to the invention is in particular a skin care formulation or a functional (anti-aging) formulation.

[0069] Examples of skin care formulations are in particular photoprotective formulations (suncare formulations), anti-aging formulations, formulations for treating photoaging, body oils, body lotions, body gels, treatment creams, skin protective ointments, moisturizing formulations such as moisturizing gels or moisturizing sprays, face and / or body moisturizers, and skin whitening formulations.

[0070] Examples of functional formulations are topical compositions containing active ingredients such as, but not limited to, hormone formulations, vitamin formulations, vegetable extract formulations, anti-aging formulations, and / or antimicrobial (antibacterial or antifungal) formulations.

[0071] Topical compositions according to the invention can take a wide variety of forms, including, but not limited to, simple solutions (e.g., aqueous, organic solvent, or oil-based), emulsions or microemulsions (especially oil-in-water (O / W) or water-in-oil (W / O), silicone-in-water (Si / W) or water-in-silicone (W / Si), PIT emulsions, multiple emulsions (e.g., oil-in-water-in-oil (O / W / O) or water-in-oil-in-water (W / O / W)) or Pickering emulsions), and solid forms (e.g., hydrogels, alcohol gels, lipogels, sticks, flowable solids, or amorphous materials).

[0072] These product forms can be used in a number of applications including, but not limited to, gels, creams, ointments, lotions, serums, powders, aerosol sprays or two-component dispensing systems.

[0073] In a preferred embodiment, the topical composition according to the invention is an emulsion and / or a gel. Even more preferably, the topical composition is an emulsion containing an oily phase and an aqueous phase, such as, in particular, an O / W, W / O, Si / W, W / Si, O / W / O, W / O / W multiple emulsion or a Pickering emulsion.

[0074] The amount of oily phase (i.e., the phase containing all fats and oils, including polar oils) present in such emulsions, for example, in particular O / W, W / O, Si / W, W / Si, O / W / O, W / O / W multiple emulsions or Pickering emulsions, is preferably at least 10% by weight, for example in the range of 10 to 60% by weight, preferably in the range of 15 to 50% by weight, most preferably in the range of 15 to 40% by weight, based on the total weight of the composition.

[0075] The oil phase according to the present invention preferably comprises an oil selected from butylene glycol dicaprylate / -dicaprate, propylene glycol dicaprylate / -dicaprate, dicaprylyl ether, C12-15 alkyl benzoate, C18-38 fatty acid triglycerides, dibutyl adipate, cyclomethicone, dimethicone, 2-phenylethyl benzoate, isopropyl lauroyl sarcosine, caprylic / capric triglyceride, and mixtures thereof.

[0076] The amount of aqueous phase present in such emulsions is preferably at least 20% by weight, for example in the range 20 to 90% by weight, preferably in the range 30 to 80% by weight, most preferably in the range 30 to 70% by weight, based on the total weight of the composition.

[0077] Advantageously, in all emulsions according to the invention, the ratio of oily phase to aqueous phase is chosen in the range from 40:60 to 30:70.

[0078] In one particularly advantageous embodiment, the topical composition according to the invention is in the form of an oil-in-water (O / W) emulsion comprising an oily phase dispersed in an aqueous phase in the presence of an O / W emulsifier. The preparation of such O / W emulsions is well known to those skilled in the art.

[0079] When the cosmetic composition according to the invention is an O / W emulsion, it advantageously contains at least one O / W or Si / W emulsifier selected from the group consisting of glyceryl stearate citrate, glyceryl stearate SE (self-emulsifying), stearic acid, salts of stearic acid, and polyglyceryl-3 methylglucose distearate. Further suitable emulsifiers are phosphate esters and their salts, such as cetyl phosphate (e.g., Amphisol® A from DSM Nutritional Products Ltd.), diethanolamine cetyl phosphate (e.g., Amphisol® DEA from DSM Nutritional Products Ltd.), potassium cetyl phosphate (e.g., Amphisol® K from DSM Nutritional Products Ltd.), sodium cetearyl sulfate, sodium glyceryl oleate phosphate, hydrogenated vegetable glycerides phosphate, and mixtures thereof. Further suitable emulsifiers include sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, cetearyl glucoside, lauryl glucoside, decyl glucoside, sodium stearoyl glutamate, sucrose polystearate, and hydrated polyisobutene. Furthermore, one or more synthetic polymers may be used as emulsifiers, such as PVP eicosene copolymer, acrylates / C10-30 alkyl acrylate crosspolymer, and mixtures thereof.

[0080] The at least one O / W type or Si / W type emulsifier is preferably used in an amount of 0.5 to 10 wt %, particularly 0.5 to 6 wt %, for example, more particularly 0.5 to 5 wt %, for example, most particularly 1 to 4 wt %, based on the total weight of the cosmetic composition.

[0081] Particularly suitable O / W emulsifiers for use in topical compositions according to the invention include phosphate ester emulsifiers, such as advantageously 8-10 alkyl ethyl phosphate, C9-15 alkyl phosphate, ceteareth-2 phosphate, ceteareth-5 phosphate, ceteth-8 phosphate, ceteth-10 phosphate, cetyl phosphate, C6-10 pareth-4 phosphate, C12-15 pareth-2 phosphate, C12-15 pareth-3 phosphate, DEA ceteareth-2 phosphate, DEA cetyl phosphate, DEA oleth-3 phosphate, potassium cetyl phosphate, deceth-4 phosphate, deceth-6 phosphate and trilaureth-4 phosphate.

[0082] A particularly suitable O / W emulsifier for use in the topical composition according to the invention is potassium cetyl phosphate, available commercially, for example, as Amphisol® K from DSM Nutritional Products Ltd Kaiseraugst.

[0083] Another particularly suitable type of O / W emulsifier is a nonionic self-emulsifying system derived from olive oil known as (INCI name) Cetearyl and Sorbitan Olivate (chemical composition: sorbitan and cetearyl esters of olive oil fatty acids), for example sold under the trade name OLIVEM 1000.

[0084] In one particular embodiment, the present invention relates to a topical composition, with all the definitions and preferences set out herein, in the form of an O / W emulsion comprising an oily phase dispersed in an aqueous phase in the presence of an O / W emulsifier, the O / W emulsifier being potassium cetyl phosphate. The amount of oily phase in such an O / W emulsion is preferably at least 10% by weight, more preferably in the range of 10 to 60% by weight, most preferably in the range of 15 to 50% by weight, for example in the range of 15 to 40% by weight, based on the total weight of the composition.

[0085] Preferably, the topical composition according to the invention further comprises at least one fatty alcohol (co-emulsifier), such as, in particular, cetyl alcohol, cetearyl alcohol and / or behenyl alcohol. The total amount of the one or several fatty alcohols in the topical composition according to the invention is preferably chosen in the range of about 0.1 to 10.0% by weight, in particular in the range of about 0.5 to 6.0% by weight, relative to the total weight of the topical composition.

[0086] Preferably, topical compositions according to the present invention contain a thickener to aid in achieving a suitable product consistency, particularly when the topical composition is in the form of an emulsion. Preferred thickeners are aluminum silicate, xanthan gum, hydroxypropyl methylcellulose, hydroxyethylcellulose, polyacrylates such as Carbopole® (e.g., Carbopole 980, 981, 1382, 2984, 5984), or mixtures thereof. Further preferred thickeners include acrylic acid / C10-30 alkyl acrylate copolymers (e.g., Pemulen TR 1, Pemulen TR 2, Carbopol 1328, etc., by NOVEON) and Aristoflex AVC (INCI: Ammonium acryloyldimethyltaurate / VP copolymer).

[0087] The topical composition according to the invention advantageously comprises a preservative, if present, preferably used in an amount of 0.1 to 2% by weight, more preferably 0.5 to 1.5% by weight, based on the total weight of the composition.

[0088] Topical compositions according to the invention generally have a pH in the range of 3 to 10, preferably a pH in the range of 4 to 8, and most preferably a pH in the range of 4 to 7.5, for example a pH in the range of 5 to 6.5. The pH can be readily adjusted as required with a suitable acid such as citric acid or a base such as sodium hydroxide (e.g., as an aqueous solution), triethanolamine (TEA Care), tromethamine (Trizma Base), and aminomethylpropanol (AMP-Ultra PC 2000), according to standard methods in the art.

[0089] The amount of cosmetic composition applied to the skin is not critical and can be easily adjusted by one skilled in the art. Preferably, the amount is 0.1 to 3 mg / cm. 2 of skin, for example, preferably 0.1 to 2 mg / cm 2 of skin area, most preferably 0.5-2 mg / cm 2 Selected for a range of skin types.

[0090] The following examples are provided to further illustrate the compositions and effects of the present invention. These examples are illustrative only and are not intended to limit the scope of the invention in any way.

[0091] [Example] 1. Preparation of dried plant extracts The dried aerial parts of each plant (preferably flowers, stems, and / or leaves) are crushed and then extracted with a solvent (an ethanol / water mixture ranging from 50% ethanol / 50% water (m / m) to 60% ethanol / 40% water) at a selected temperature ranging from room temperature to 60° C. for 1 to 3 hours. After filtration, the hydroalcoholic extract is collected and concentrated under vacuum at a temperature of 50 to 70° C. until a dry extract is obtained.

[0092] 2. Cultivation of senescent cells Normal and senescent cell populations were obtained from normal human dermal fibroblasts. For the normal cell population, cells were seeded in cell culture medium (Dulbecco's modified Eagle's medium supplemented with 10% serum and 1% antibiotics) and allowed to adhere and grow in a humidified cell incubator maintained at 37°C and 5% CO2. They were then passaged or harvested when they reached 90% confluence. For the senescent cell population, normal fibroblasts were briefly exposed to 200 μM H2O2 at this stage, followed by exposure to normal cell culture medium. After several days, the cells were again treated with H2O2 to obtain a fully senescent population.

[0093] [3. Senescent cell elimination activity test] Both the normal and senescent populations were mixed to form a 70% normal and 30% senescent cell population to form the treatment population. The 70% normal and 30% senescent cell populations were then seeded in cell culture medium and allowed to attach in a cell incubator. After attachment, the medium was aspirated, and treatment medium (Dulbecco's modified Eagle's medium supplemented with 1% serum) containing various concentrations of each dried plant extract (see Table 1) was added to the cells. For controls, there was one condition containing only treatment medium without compound (negative control) and one condition containing navitoclax, a known senolytic agent (positive control). The cells were incubated in the cell incubator for at least 72 hours. Senescence-associated β-galactosidase (a well-known senescence marker) was then visualized in cells using flow cytometry to quantify senescence levels. The results are shown in Table 1.

[0094] [result] The experiments showed that plant extracts from Epilobium fleischeri, but not from Artemisia umbelliformis, Leontopodium alpinum, Eryngium alpinum, and Asparagus officinalis, showed significant senolytic effects and reduced the percentage rate of senescence in human dermal fibroblasts (see Table 1).

[0095] [Table 1]

Claims

1. Cosmetic use of an extract of Epilobrium fleicheri as an active ingredient for the treatment of signs of aging by selectively eliminating senescent skin cells.

2. The use according to claim 1 , wherein the senescent skin cells are human dermal fibroblasts.

3. 3. The use according to claim 1 and / or 2, wherein the senescent cells are senescence-associated senescent cells, stress-associated senescent cells, or both.

4. 4. The use according to any one of claims 1 to 3, wherein the treatment of the signs of ageing is the treatment of fine lines, wrinkles, crow's feet, sagging skin, thinning of the skin, age spots, and improving skin elasticity or skin firmness.

5. 5. Use according to any one of claims 1 to 4, wherein the Epilobium fleischeri extract is an aqueous or dry extract obtained from the flowers, leaves, seeds and / or stems of the plant Epilobium fleischeri.

6. 6. The use according to claim 5, wherein the Epilobium fleischeri extract consists essentially of (i) 5 to 10% by weight, based on the dry matter of the Epilobium fleischeri flower, leaf, and stem extract, (ii) 25 to 50% by weight of water, (iii) less than 50% by weight of glycerin, and (iv) 0.1 to 2% by weight of citric acid and / or potassium sorbate.

7. 7. The use according to any one of claims 1 to 6, wherein the Epilobium fleischeri extract is administered in the form of a topical composition comprising an effective amount of the Epilobium fleischeri extract and a cosmetically acceptable carrier.

8. 8. Use according to claim 7, wherein the carrier consists of at least 30% by weight, more preferably at least 40% by weight, most preferably at least 45% by weight of water, for example, in particular 50 to 90% by weight of water.

9. 9. Use according to claim 7 and / or 8, wherein the topical composition comprises 0.001 to 10% by weight, preferably 0.01 to 8% by weight, even more preferably 0.1 to 7% by weight, even more preferably 0.1 to 5% by weight, and still more preferably 0.1 to 3% by weight of the Epilobium fleischeri extract, based on the total weight of the topical composition.

10. Use according to any one of claims 7 to 9, wherein the topical composition is a leave-on or rinse-off composition, preferably a leave-on composition.

11. The use according to any one of claims 7 to 10, wherein the composition is an O / W emulsion comprising an oily phase dispersed in an aqueous phase.

12. 1. A cosmetic skin and scalp care method for selectively removing senescent cells in the skin and / or hair follicles, comprising applying to the skin or scalp in need thereof at least an effective amount of an extract of Epilobium fleischeri; or a composition comprising at least said extract.

13. The method of claim 12, wherein the senescent cells are senescent human dermal fibroblasts.

14. The effective amount (based on dry matter) of the Epilobium fleischeri extract applied to the skin cells is ２ The method according to claim 12 and / or 13, wherein the amount of the hydroxybenzoate is selected in the range of 0.001 to 1% by weight per 1000 mg of the hydroxybenzoate.

15. The method according to any one of claims 12 to 14, wherein the number of senescent cells is reduced by at least 20%, preferably by at least 25%, most preferably by at least 30%.