A method for treating a condition associated with acne and / or hyperkeratosis

Abstract

To provide a method of treating a state associated with acne and / or hyperkeratinization.SOLUTION: The method comprises topically applying, to skin in need of treatment, a composition comprises 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester. Optionally, the 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester constitutes up to 20 wt.% of the composition. Optionally, the composition also comprises a cosmetically acceptable carrier.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a composition having retinoid-like activity and a method of using the composition for treating human tissues including skin, hair, nails, oral mucosa, nasal mucosa, vaginal mucosa and the like.

Background Art

[0002] Human skin undergoes certain aging processes, some of which are due to endogenous processes (e.g., aging over time) and some are due to exogenous factors (e.g., photoaging). In addition, temporary or even persistent changes to the skin can occur, such as acne, oily or dry skin, keratosis, rosacea, photosensitivity, inflammatory, erythematous, and allergic or autoimmune reactive responses, such as dermatitis and photosensitivity dermatosis.

[0003] As a result of the above aging processes, thinning of the skin, weakening of the interface between the epidermis and dermis, and a decrease in the number of cells and blood supply vessels can be mentioned. This often results in the formation of fine lines and wrinkles, and pigmentation defects may occur.

[0004] Retinoids have been used to treat skin conditions caused by endogenous aging, exogenous factors, or skin diseases. However, despite the beneficial effects of retinoid treatment, its benefits are limited due to skin irritation by retinoids. These side effects may limit the use of retinoids. All retinoids used in cosmetic products are synthetically derived, and there is a great acceptance among cosmetic users for natural compounds having retinoid-like activity and skin treatment effects.

[0005] So far, the search for alternative or natural compounds to replace retinoids has met with some success in the treatment of skin conditions related to aging such as skin atrophy and photoaging, and in the reduction of the appearance of wrinkles, fine lines, stretch marks, or cellulite.

[0006] U.S. Patent Application No. 9,220,928, assigned to Ecobiotics LTD, discloses compounds derived from plants of the genus Acronicta containing 3-(4-farnesyloxyphenyl)-propionic acid for use as antioxidants, antibacterial agents, anthelmintics, and as components of anti-inflammatory agents, cancer chemopreventive agents, food additives and / or fragrances. However, this patent does not identify the anti-aging properties associated with the compositions therein.

[0007] U.S. Patent Application Publication No. 2013 / 0259815, assigned to Johnson&Johnson Consumer Companies,Inc., discloses a method of whitening the skin by applying to the skin a plant extract containing a specific aromatic compound or a plant of the genus Acronicta containing such a compound.

[0008] Applicants have unexpectedly discovered that certain extracts, including plant extracts from plants of the genera Acronicta, Ricaria, Caltha, and Rheum, and bacterial extracts from the genus Actinomyces, exhibit retinoid-like bioactivity and / or other desirable properties for use in skin and other human tissues. Such extracts can be used topically to provide significant anti-aging, skin barrier improvement and moisturization, anti-acne, and other benefits normally associated with retinol. Such extracts may be used, for example, on oral mucosa, nasal mucosa, and vaginal mucosa. SUMMARY OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION

[0009] The present invention relates to extracts that exhibit retinoid-like bioactivity, for example, in the skin, and includes upregulation of retinoid-responsive genes such as RARg, CRABP2, HbEGF, HAS3, and UGCG in human skin explant cultures. Further, the present invention relates to methods of treating signs of aging, improving skin barrier function, and providing an anti-acne effect using such plant or bacterial extracts. MEANS FOR SOLVING THE PROBLEMS

[0010] The present invention relates to a method for treating signs of skin aging, which comprises topically applying to the skin in need of treatment for signs of skin aging a composition comprising an extract selected from the group consisting of an extract of Acronychia acidula, an extract of Licaria vernicosa, an extract of Calendula officinalis, an extract of Trigonella foenum - graecum, an extract of bacteria of the genus Actinomyces, and combinations thereof.

[0011] The present invention also relates to a method for improving skin barrier properties, which comprises topically applying to the skin in need of improvement of skin barrier function and moisturization a composition comprising an extract selected from the group consisting of an extract of Acronychia acidula, an extract of Licaria vernicosa, an extract of Calendula officinalis, an extract of Trigonella foenum - graecum, an extract of bacteria of the genus Actinomyces, and combinations thereof.

[0012] The present invention further relates to a method for treating acne, which comprises topically applying to the skin in need of treatment for acne a composition comprising an extract selected from the group consisting of an extract of Acronychia acidula, an extract of Licaria vernicosa, an extract of Calendula officinalis, an extract of Trigonella foenum - graecum, an extract of bacteria of the genus Actinomyces, and combinations thereof.

[0013] The present invention relates to a method for treating signs of skin aging, which comprises topically applying to the skin in need of treatment for signs of skin aging a composition comprising an extract of Acronychia acidula.

[0014] The present invention also relates to a method for improving skin barrier properties, which comprises topically applying to the skin in need of improvement of skin barrier function and moisturization a composition comprising an extract of Acronychia acidula.

[0015] The present invention further relates to a method for treating acne, which comprises topically applying to the skin in need of acne treatment a composition containing an extract of Acronicta acidaula.

[0016] The present invention also relates to a method for treating signs of skin aging, which comprises topically applying to the skin in need of treatment of signs of skin aging a composition containing an extract of Ricalia vernicosa.

[0017] The present invention also relates to a method for improving skin barrier properties, which comprises topically applying to the skin in need of improving skin barrier function and moisturization a composition containing an extract of Ricalia vernicosa.

[0018] The present invention further relates to a method for treating acne, which comprises topically applying to the skin in need of acne treatment a composition containing an extract of Ricalia vernicosa.

[0019] The present invention also relates to a method for treating signs of skin aging, which comprises topically applying to the skin in need of treatment of signs of skin aging a composition containing an extract of Celosia cristata.

[0020] The present invention also relates to a method for improving skin barrier properties, which comprises topically applying to the skin in need of improving skin barrier function and moisturization a composition containing an extract of Celosia cristata.

[0021] The present invention further relates to a method for treating acne, which comprises topically applying to the skin in need of acne treatment a composition containing an extract of Celosia cristata.

[0022] The present invention also relates to a method for treating signs of skin aging, which comprises topically applying to the skin in need of treatment of signs of skin aging a composition containing an extract of Colocasia esculenta.

[0023] The present invention also relates to a method for improving skin barrier properties, which comprises topically applying to the skin in need of improving skin barrier function and moisturization a composition containing an extract of Colocasia esculenta.

[0024] The present invention further relates to a method for treating acne, which comprises topically applying a composition containing an extract of Colla Cortex Eucommiae to the skin in need of acne treatment.

[0025] The present invention also relates to a method for treating signs of skin aging, which comprises topically applying a composition containing an extract of Actinomyces bacteria to the skin in need of treatment of signs of skin aging.

[0026] The present invention also relates to a method for improving skin barrier properties, which comprises topically applying a composition containing an extract of Actinomyces bacteria to the skin in need of improvement of skin barrier function and moisturization.

[0027] The present invention further relates to a method for treating acne, which comprises topically applying a composition containing an extract of Actinomyces bacteria to the skin in need of acne treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0028]

Figure 1

Figure 2

[0029] Those skilled in the art are considered to be able to utilize the present invention to the maximum extent based on the description in this specification. The following specific embodiments should be construed as illustrative only and should not be construed as limiting the following disclosure in any sense.

[0030] Unless otherwise indicated, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Further, all publications, patent applications, patents, and other references cited herein are incorporated by reference in their entirety. When used in this specification, all percentages are by weight / volume of the total composition unless otherwise specified.

[0031] The term As used herein, a composition that "essentially does not contain" a certain component means that the composition contains no more than about 2% by weight of that component based on the total weight of the composition. In one embodiment, a composition that essentially does not contain a certain component contains no more than about 1% by weight, more preferably no more than about 0.5% by weight, more preferably no more than about 0.1% by weight, more preferably no more than about 0.05% by weight, and more preferably no more than about 0.01% by weight of that component based on the total weight of the composition. In certain embodiments, a composition that essentially does not contain a certain component does not contain that component, i.e., the component is not present in the composition.

[0032] As used herein, "cosmetically acceptable" means that the component described by this term is suitable for use in contact with tissue (e.g., skin or hair) without undue toxicity, incompatibility, instability, irritation, allergic reaction, etc. As will be recognized by those skilled in the art, cosmetically acceptable salts are acidic / anionic or basic / cationic salts. Examples of cosmetically acceptable salts derived from inorganic bases include salts of sodium or potassium, etc. Examples of cosmetically acceptable salts derived from organic bases include salts formed with primary, secondary, or tertiary amines, etc.

[0033] As used herein, "cosmetic" specifically refers to a beauty substance or preparation that, when related to the appearance of tissue or skin, maintains, restores, imparts, adorns, enhances, or appears to increase beauty or youthfulness to achieve a physically beautiful appearance.

[0034] As used herein, the term "safe and effective amount" means an amount that is sufficient to induce the desired effect but is sufficiently low to avoid serious side effects. The safe and effective amount of a compound, extract, or composition will vary depending on, for example, the age, health, and environmental exposure of the end user, the duration and nature of the treatment, the specific compound, extract, ingredient, or composition being used, the specific cosmetically acceptable carrier being used, and like factors.

[0035] As used herein, "treatment" or "treating" means the amelioration, prevention, or cure of a condition, disease or disorder, or at least one recognizable symptom thereof. In one embodiment, "treatment" or "treating" refers to the amelioration, prevention, or cure of at least one measurable physical parameter associated with a condition, disease, or disorder being treated, which may not necessarily be recognizable in or by the subject being treated. In another embodiment, "treatment" or "treating" refers to inhibiting or delaying the progression of a condition, disease or disorder, either physically (e.g., stabilization of a recognizable symptom) or physiologically (e.g., stabilization of a physical parameter), or both. In another embodiment, "treatment" or "treating" refers to delaying the onset of a condition, disease or disorder.

[0036] In certain embodiments, the compositions of the invention are administered as a prophylactic measure. As used herein, "prophylaxis" or "prophylactic" means reducing the risk of contracting a given condition, disease, or disorder.

[0037] The compositions of the invention are suitable for treating or preventing signs of skin aging. As used in the present invention, "signs of skin aging" include the presence of fine lines and wrinkles, loss of elasticity, uneven skin, and pigmentation. In particularly preferred embodiments, the signs of aging are the presence of fine lines and wrinkles and / or loss of elasticity.

[0038] As used herein, "wrinkle" includes fine wrinkles, fine lines, or coarse wrinkles. Examples of wrinkles include, but are not limited to, fine wrinkles around the eyes (e.g., "crow's feet"), wrinkles on the forehead and cheeks, frown lines between the eyebrows, and laugh lines around the mouth.

[0039] The composition of the present invention is suitable for improving the texture of the skin or improving the firmness of the skin.

[0040] As used herein, "improvement of skin texture" means smoothing the surface of the skin to remove either ridges or cracks on the skin surface.

[0041] As used herein, "improvement of skin firmness" means enhancing the firmness or elasticity of the skin, preventing the loss of firmness or elasticity of the skin, or preventing or treating sagging, relaxation, and loose skin.

[0042] As used herein, "loss of elasticity" includes loss of elasticity or structural integrity of the skin or tissue, including but not limited to sagging, relaxation, and loose tissue. Loss of elasticity, or loss of structural integrity of the tissue, can be the result of a number of factors, including but not limited to disease, aging, hormonal changes, mechanical trauma, environmental damage, or application of products such as cosmetics or pharmaceuticals to the tissue.

[0043] As used herein, "non-uniform skin" means a skin condition associated with diffuse or mottled pigmentation that can be classified as hyperpigmentation such as post-inflammatory hyperpigmentation.

[0044] As used herein, "blemish" means a skin condition associated with redness or erythema.

[0045] As used herein, "age spots" means a skin condition associated with individual pigmentation, e.g., small areas of darker pigmentation that can occur on the face and hands.

[0046] Signs of skin aging also include a decrease in skin thickness and the presence of abnormal or decreased synthesis of glycoproteins including collagen, glycosaminoglycans, proteoglycans, elastin, or fibronectin. In one embodiment, the signs of aging are selected from abnormal or decreased synthesis of glycoproteins including collagen, glycosaminoglycans, proteoglycans, elastin, or fibronectin. In another embodiment, the sign of skin aging is a decrease in the synthesis of collagen or elastin.

[0047] The composition is also suitable for the treatment or prevention of acne. As used herein, "acne" refers to a disorder resulting from the action of hormones and other substances in the sebaceous glands and hair follicles, typically resulting in clogged pores and the formation of inflammatory or non-inflammatory lesions on the skin. In particular, this relates to scars, lesions, or eruptions, pre-emergent pimples, blackheads, and / or whiteheads. As used herein, "pre-emergent pimples" are inflammatory vesicles that are not visually apparent to the naked eye (e.g., as a lesion) on the surface of the skin.

[0048] The composition of the present invention is also suitable for the treatment or prevention of rosacea. As used herein, "rosacea" means skin having persistent erythema, with or without papules, pustules, or nodules.

[0049] The composition of the present invention is also suitable for treating skin that requires improvement in skin barrier function and moisturization. As used in the present invention, "skin that requires improvement in skin barrier function and moisturization" means skin that is lacking in moisture, lacking in sebum, cracked, dry, itchy, scaly, xerotic, dehydrated, lacking in flexibility, lacking in luster, dull, or lacking in lipids, but is not limited thereto.

[0050] The composition of the present invention is also suitable for enhancing the endogenous hyaluronic acid (HA) level in the skin, and provides improvement in moisture replenishment and the appearance of at least one sign of skin aging. The topical use of the composition can increase the level of hyaluronic acid in the direction seen in younger skin, thereby reducing the appearance of signs of skin aging by providing structural support to the skin.

[0051] The composition of the present invention is also suitable for reducing hyperkeratinization of the epidermis. Thus, the composition can be used for the treatment or prevention of conditions characterized by hyperkeratinization such as acne or warts.

[0052] The composition is also suitable for treating or preventing such skin conditions as cutaneous relaxation (elastin-related disease), scleroderma / systemic sclerosis (collagen-related disease), keratosis pilaris, cellulite, stretch marks, psoriasis, warts, Kaposi's sarcoma, and cutaneous T-cell lymphoma.

[0053] The composition of the present invention is also suitable for application to the oral mucosa. The composition can be applied to the oral mucosa that requires an increase in the induction of mucin, an increase in the induction of hyaluronic acid, an improvement in the barrier, or an improvement in the tight junction.

[0054] The composition is further suitable for the treatment or prevention of asthma, allergy, and itching. For example, the composition can be applied topically to the skin or intranasally to the nasal mucosa for such purposes.

[0055] Plant extract The inventors have unexpectedly identified a plant extract having retinol-like bioactivity. The extract is obtained from plants including, for example, plants of the genus Acronicta, Rikaria, Caltha, and Rheum.

[0056] Examples of plants of the genus Acronychia include, for example, Acronychia aberrans, Acronychia acidula, Acronychia acronychioides, Acronychia acuminate, Acronychia baeuerlenii, Acronychia chooreechillum, Acronychia crassipetala, Acronychia eungellensis, Acronychia imperforate, Acronychia laevis, Acronychia laurifolia, Acronychia littoralis, Acronychia oblongifolia, Acronychia octandra, Acronychia parviflora, Acronychia pauciflora, Acronychia pedunculata, Acronychia pubescens, Acronychia species (Batavia Downs), Acronychia suberosa, Acronychia vestita, and Acronychia wilcoxiana.

[0057] In one embodiment, the extract is obtained from Acronychia acidula. The common names of Acronychia acidula are lemon aspen, hard aspen, and lemonwood. The Latin synonym names of Acronychia acidula are Jambolifera acidula and Acronychia superba.

[0058] Examples of plants of the genus Licaria include Licaria vernicosa, Licaria brittoniana, Licaria canella, Licaria cubensis, Licaria velutina, and Licaria triandra. There are about 40 species reported in the genus Licaria, which are endemic to Central and South America.

[0059] In one embodiment, the extract is obtained from Licaria vernicosa.

[0060] Examples of plants of the genus Calendula include 15 - 20 species such as Calendula. The known synonyms of Calendula are Calendula aurantiaca, Calendula eriocarpa, Calendula hydruntina, Calendula prolifera, Calendula×santamariae, and Caltha officinalis.

[0061] In one embodiment, the extract is obtained from Calendula. The common names of Calendula are pot marigold, calendula, common marigold, and Scotch marigold.

[0062] As plants of the genus Trigonella, 36 known species can be mentioned, for example, Trigonella foenum-graecum, Trigonella balansae, Trigonella corniculata, Trigonella maritima, Trigonella spicata, Trigonella caerulea, Trigonella occulta, Trigonella polycerata, Trigonella Calliceras, and Trigonella Cretica. Trigonella foenum-graecum or herb fenugreek is the best-known species of the genus Trigonella.

[0063] In one embodiment, the extract is obtained from Trigonella foenum-graecum. The common names of Trigonella foenum-graecum are fenugreek, Greek hay, Greek clover, bird's foot, fenugrec, hu lu ba, Trigonella, and bockshornklee.

[0064] Any of various extracts of Acronychia, Richea, Calendula, or Trigonella can be used. One extract or a combination of extracts can be used.

[0065] The extract can be obtained from any part of the plant such as fruits, seeds, bark, leaves, flowers, petals, roots, and xylem. In certain embodiments, the extract is obtained from the fruits, xylem, petals, or leaves of the plant.

[0066] In one embodiment, the extract is derived from the fruits of Acronychia acidula.

[0067] In another embodiment, the extract is derived from the xylem of Richea vernicosa.

[0068] In a further embodiment, the extract is derived from the roots of Richea vernicosa.

[0069] In another embodiment, the extract is derived from the petals of celosia.

[0070] In another embodiment, the extract is derived from the leaves of coloha.

[0071] In certain embodiments, the acronictia and / or ricalia extracts useful in the present invention contain compounds of the following formula:

[0072]

Chemical formula

[0073]

Chemical formula

[0074] In certain embodiments, the Acronicta and / or Lycaena extracts useful in the present invention contain the following formula:

[0075]

Chemical formula

[0076] In certain embodiments, at least one of the compounds of the above formula is present in the Acronicta and / or Lycaena extract at a concentration of 1 wt% or more (or about 1 wt%) to about 20%, or optionally about 7 wt% (or about 7 wt%) to about 10% (or about 10 wt%) of the Acronicta and / or Lycaena extract.

[0077] In certain embodiments, the compound of the above formula is in the form of an acid or an alkyl ester selected from (or selected from the group consisting of) 3-(4-farnesyloxyphenyl)-propionic acid, 3-(4-farnesioxy-3-hydroxyphenyl)-propionic acid, 3-(4-farnesioxy-3-methoxyphenyl)-propionic acid, alkyl esters thereof, particularly ethyl esters thereof, and combinations of two or more thereof.

[0078] In certain embodiments, the compound of the above formula is 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester.

[0079] In certain embodiments, 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester is present in the extract of Acronychia and / or Licaria at a concentration of 1 wt% or more (or about 1 wt%) to about 20%, or optionally about 7 wt% (or about 7 wt%) to about 10% (or about 10 wt%) of the extract of Acronychia and / or Licaria.

[0080] 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester can be synthesized using conventional organic synthesis processes.

[0081] Thus, in one embodiment, a composition containing 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester is used. Such a composition can be used in any method of the present invention. In certain embodiments, the composition may contain 1 wt% or more (or about 1 wt%) to about 20 wt%, or optionally about 7 wt% (or about 7 wt%) to about 10 wt% (or about 10 wt%) of 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester based on the total weight of the composition.

[0082] Suitable extracts can be obtained using conventional methods including, but not limited to, direct extraction of materials from biomass by grinding, disintegration, pressing, squeezing, crushing, centrifugation, and / or cold perfusion, stirring / distillation, microwave-assisted extraction, supercritical / subcritical CO2 compressed gas extraction, pressurized solvent extraction, accelerated solvent extraction, pressurized or normal hot water extraction, surfactant-assisted warm water extraction, oil extraction, membrane extraction, Soxhlet extraction, finger distillation / extraction, and / or, for example, by the processes disclosed in U.S. Pat. Nos. 7,442,391, 7,473,435, and 7,537,791, incorporated herein by reference, or by Integrated Botanical Technologies, LLC, or by other methods such as solvent extraction.

[0083] Any of a variety of solvents including polar solvents, non-polar solvents, or combinations of two or more thereof can be used in methods including solvent extraction. Suitable polar solvents include polar inorganic solvents such as water, polar organic solvents such as alcohols and corresponding organic acids, for example, C1-C8 alcohols including methanol, ethanol, propanol, butanol, etc., and organic acids including acetic acid, formic acid, propanoic acid, etc., polyols and glycols including C1-C8 polyols / glycols, and combinations of two or three or more thereof. Suitable non-polar solvents include alkanes including C1-C8 alkanes, cycloalkanes including C1-C8 alkanes, alkyl ethers including C1-C8 alkyl ethers, petroleum ether, ketones including C1-C8 ketones, methylene chloride, ethyl acetate, xylene, toluene, chloroform, vegetable oils, mineral oils, and other non-polar organic solvents such as ketones. In another embodiment, the extraction can be obtained by supercritical fluid extraction with or without using the above non-polar solvents or polar modifiers such as C1-C8 alcohols, water, C1-C8 polyols / glycols or C1-C8 organic acids.

[0084] In one embodiment, the extract comprises an extract of Acronychia acidula. In another embodiment, the extract of the present invention comprises a combination of polar and non-polar extracts of the fruit of Acronychia acidula. In another embodiment, the extract of the present invention comprises an alcohol extract or a glycol extract of the fruit of Acronychia acidula.

[0085] In one embodiment, the extract comprises an extract of Richea velutina. In another embodiment, the extract of the present invention comprises a combination of polar and non-polar extracts of the xylem of Richea velutina or the roots of Richea velutina. In another embodiment, the extract of the present invention comprises an alcohol extract of the wood of Richea velutina or the roots of Richea velutina.

[0086] In another embodiment, the extract is a polar extract prepared using a polar solvent comprising water, a C1-C8 alcohol, a C1-C8 polyol, or a C1-C8 glycol, or a combination of two or more thereof. In a particular embodiment, the extract is extracted using one or two or more C1-C4 alcohols, C1-C4 polyols, and / or C1-C4 glycols. In a particular embodiment, the extract is prepared using a solvent comprising these combinations in the presence or absence of methanol, ethanol, or water.

[0087] In another embodiment, the extract is a polar extract extracted from the fruit of Acronychia acidula using a combination of alcohol and water.

[0088] In yet another embodiment, the extract is a polar extract extracted from the ground xylem of Richea velutina or the ground roots of Richea velutina using methanol.

[0089] In one embodiment, the extract comprises an extract of Carthamus tinctorius. In another embodiment, the extract of the present invention comprises a combination of polar and non-polar extracts of the petals of Carthamus tinctorius. In another embodiment, the extract of the present invention comprises a non-polar extract of the petals of Carthamus tinctorius.

[0090] In one embodiment, the extract comprises an extract of fenugreek. In another embodiment, the extract of the present invention comprises a combination of polar and non-polar extracts of fenugreek leaves. In another embodiment, the extract of the present invention comprises a non-polar extract of fenugreek leaves.

[0091] In yet another embodiment, the extract is a non-polar extract prepared using a non-polar solvent comprising one or more C1-C8 alkanes, C1-C8 cycloalkanes, C1-C8 alkyl ethers, C1-C8 alkyl esters and / or chloroform, more preferably one or more C1-C8 alkanes, C1-C8 alkyl esters and / or chloroform.

[0092] In yet another embodiment, the extract is a non-polar extract prepared using hexane, ethyl acetate, chloroform, or a mixture of two or more thereof. In yet another embodiment, the extract is a non-polar extract prepared using ethyl acetate.

[0093] In one embodiment, the plant extract can be obtained by extracting cell cultures of various plants including cell cultures of the genus Acronychia, the genus Licaria, the genus Calendula and / or the genus Rehmannia. The cell cultures extracted to obtain the plant extract used in the present invention may be in any form including suspension cell cultures and the like.

[0094] Bacterial extract The inventors have unexpectedly identified bacterial extracts having retinol-like bioactivity. Actinomycetes bacteria include many species that are fully characterized, as well as several species that are not well characterized, such as one species collected from the United States and labeled as A5640. A sample of this bacterium is collected, grown in culture, and made into an extract. The extract is currently part of a natural product collection under the management of the Baruch S. Blumerg Institute, Doylestown, PA (formerly known as the Institute of Hepatitis Virus Research Labs (IHVR)). In one embodiment, the extract is obtained from an Actinomycetes species having the ability to produce a chemical composition similar to that produced by extract A5640. In another embodiment, the bacterium is collected in the United States and the strain is the same as the pre-assigned species A5640.

[0095] Composition In one embodiment, the method of the present invention comprises applying to a tissue in need of treatment a composition comprising a plant or bacterial extract described herein. Such a tissue may be, for example, human skin, hair, nails, oral mucosa, nasal mucosa, or vaginal mucosa. Such a tissue may need treatment or prevention of a disease or condition treatable or preventable by retinoids, preferably retinol.

[0096] Preferably, the method of the present invention comprises administering to a tissue in need of treatment a composition comprising a safe and effective amount of the extract of the present invention. In the case of skin in need of anti-aging treatment, such an extract in an anti-aging effective amount can be used.

[0097] In one embodiment, the method comprises applying to the tissue in need thereof an extract in an amount of greater than 0 wt% to about 20 wt% based on the total weight of the composition. In another embodiment, the method comprises applying to the tissue in need thereof an extract in an amount of about 0.0001 wt% to about 20 wt%, or about 0.001 wt% to about 10 wt%, or about 0.01 wt% to about 5 wt%, or about 0.1 wt% to about 5 wt%, or about 0.2 wt% to about 2 wt% based on the total weight of the composition. In yet another embodiment, the method comprises applying to the tissue in need thereof an extract in an amount of greater than 0 wt% to about 1 wt%, or about 0.0001 wt% to about 1 wt%, or about 0.001 wt% to about 1 wt%, or about 0.01 wt% to about 1 wt% based on the total weight of the composition.

[0098] Any suitable carrier can be used depending on the route of administration, i.e., depending on whether it is topical, oral, buccal, intranasal, periodontal, or vaginal. Preferably, in a topical composition, the carrier is a cosmetically acceptable carrier. As will be appreciated by those skilled in the art, a cosmetically acceptable carrier is a carrier that is suitable for use in contact with the body, such as the skin, hair, or nails, without undue toxicity, incompatibility, instability, irritation, allergic response, etc.

[0099] A safe and effective amount of the carrier is used in the composition. For example, the carrier is about 50% to about 99.999% of the composition, preferably about 80% to about 99.9%, more preferably about 99.9% to about 95%, and most preferably about 99.8% to about 98%. The carrier can be in a wide variety of forms. For example, emulsion carriers including, but not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and silicone-in-water-in-oil emulsions are useful herein. These emulsions can cover a wide range of viscosities, for example, from about 100 cP to about 200,000 cP.

[0100] Examples of suitable cosmetically acceptable carriers include cosmetically acceptable solvents, as well as materials for cosmetic solutions, suspensions, lotions, creams, serums, essences, gels, toners, sticks, sprays, ointments, cleansing liquids and solid soaps, shampoos, hair conditioners, pastes, foams, mousses, powders, shaving creams, wipes, patches, strips, powdered patches, microneedle patches, bandages, hydrogels, film-forming products, facial and skin masks, makeup, liquid drops, etc. The types of these products can contain several types of cosmetically acceptable carriers including, but not limited to, emulsions such as solutions, suspensions, microemulsions and nanoemulsions, gels, solids, liposomes, other encapsulation techniques, etc.

[0101] The following are non-limiting examples of such carriers. Those skilled in the art can also incorporate other carriers. In one embodiment, the carrier contains water. In a further embodiment, the carrier may further contain one or more aqueous or organic solvents. Examples of organic solvents include, but are not limited to, dimethyl isosorbide, isopropyl myristate, cationic, anionic, and non-ionic surfactants, vegetable oils, mineral oils, waxes, gums, synthetic and natural gelling agents, alkanols, glycols, and polyols. Examples of glycols include, but are not limited to, glycerin, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, polyethylene glycol, polypropylene glycol, diethylene glycol, triethylene glycol, capryl glycol, glycerol, butanediol and hexanetriol, and copolymers or mixtures thereof. Examples of alkanols include those having from about 2 to about 12 carbon atoms (e.g., from about 2 to about 4 carbon atoms) such as isopropanol and ethanol, but are not limited thereto. Examples of polyols include those having from about 2 to about 15 carbon atoms (e.g., from about 2 to about 10 carbon atoms) such as propylene glycol, but are not limited thereto. The organic solvent may be present in the carrier in an amount of about 1 percent to about 99.99 percent (e.g., about 20 percent to about 50 percent) based on the total weight of the carrier. Water may be present in the carrier in an amount of about 5% to about 95% (e.g., about 50% to about 90%) based on the total weight of the carrier (before use). The solution can contain any suitable amount of solvent, including from about 40 to about 99.99%. In one embodiment, the solution contains from about 50% to about 99.9%, from about 60% to about 99%, from about 70% to about 99%, from about 80% to about 99%, or from about 90% to about 99%.

[0102] The lotion can be made from such a solution. The lotion typically contains at least one skin softening agent in addition to a solvent. The lotion can contain from about 1% to about 20% (e.g., from about 5% to about 10%) of the skin softening agent and from about 50% to about 90% (e.g., from about 60% to about 80%) of water. As used herein, "skin softening agent" refers to a material used for preventing or reducing dryness and for protecting the skin or hair. Examples of skin softening agents include, but are not limited to, those described in the International Cosmetic Ingredient Dictionary and Handbook, eds. Wenninger and McEwen, pp. 1656 - 61, 1626, and 1654 - 55 (The Cosmetic, Toiletry, and Fragrance Assoc, Washington, D.C., 7th Edition, 1997) (hereinafter, "ICI Handbook").

[0103] Another type of product that can be formulated from the solution is a cream. The cream typically contains from about 5% to about 50% (e.g., from about 10% to about 20%) of the skin softening agent(s) and from about 45% to about 85% (e.g., from about 50% to about 75%) of water.

[0104] Furthermore, another type of product that can be formulated from the solution is an ointment. The ointment can contain a simple base of animal oil, vegetable oil, or synthetic oil, or a semi - solid hydrocarbon. The ointment can contain from about 2% to about 10% of the skin softening agent(s) and from about 0.1% to about 2% of the thickening agent(s).

[0105] The compositions useful in the present invention can also be formulated as an emulsion. When the carrier is an emulsion, about 1% to about 10% (e.g., about 2% to about 5%) of the carrier contains an emulsifier. The emulsifier can be non - ionic, anionic, or cationic. Examples of emulsifiers include, but are not limited to, those described in pp. 1673 - 1686 of the ICI Handbook.

[0106] Lotions and creams can be formulated as emulsions. Typically, such lotions contain from 0.5% to about 5% of an emulsifier, and such creams typically contain from about 1% to about 20% (e.g., from about 5% to about 10%) of a skin softening agent. They contain from about 20% to about 80% (e.g., from about 30% to about 70%) of water and from about 1% to about 10% (e.g., from about 2% to about 5%) of an emulsifier(s).

[0107] Oil-in-water and water-in-oil single-phase emulsion skin care formulations such as lotions and creams are well known in the art and are useful in the present invention. Multiphase emulsion compositions such as water-in-oil-in-water or oil-in-water-in-oil are also useful in the present invention. Generally, such single-phase or multiphase emulsions contain water, a skin softening agent, and an emulsifier as essential components.

[0108] The compositions of the present invention can also be formulated as gels (e.g., aqueous, alcoholic, alcohol / water, or oil gels using suitable gelling agents). Suitable gelling agents for aqueous and / or alcoholic gels include, but are not limited to, natural rubbers, polymers and copolymers of acrylic acid and acrylates, and cellulose derivatives (e.g., hydroxymethyl cellulose and hydroxypropyl cellulose). Suitable gelling agents for oils (such as mineral oil) include, but are not limited to, hydrogenated butylene / ethylene / styrene copolymers and hydrogenated ethylene / propylene / styrene copolymers. Such gels typically contain from about 0.1 wt% to 5 wt% of such a gelling agent.

[0109] The compositions of the present invention can also be formulated into solid formulations (e.g., wax-based sticks, solid soap compositions, powders, or wipes). The compositions of the present invention can also be combined with solid, semi-solid or soluble substrates (e.g., wipes, masks, pads, gloves, or strips).

[0110] The composition of the present invention may further contain one or more additional cosmetic active agents. As used herein, "cosmetic active agent" is a compound having a cosmetic or therapeutic effect on human tissues such as skin, hair, nails, or mucous membranes. Examples of suitable additional cosmetic active agents include skin whitening agents, melanizing agents, anti-acne agents, gloss modifiers, anti-yeast agents, anti-fungal agents and anti-bacterial agents such as antimicrobial agents, anti-inflammatory agents, anti-parasitic agents, topical analgesics, sunscreens, light protectants, antioxidants, keratolytics, detergents / surfactants, moisturizers, nutrients, vitamins, energy enhancers, antiperspirants, skin astringents, deodorants, depilatory agents, hair growth enhancers, hair growth retardants, stabilizers, hydration promoters, efficacy enhancers, anti-wrinkle agents, skin conditioning agents, anti-cellulite agents, fluoride, tooth whitening agents, tartar inhibitors, and tartar solubilizers, malodor masking agents such as malodor preventers or pH modifiers, and the like.

[0111] Examples of various suitable additional cosmetically acceptable active substances include hydroxy acids, benzoyl peroxide, D-panthenol, UV filters such as, but not limited to, avobenzone (Parsol 1789), bisdisulzole disodium (Neo Heliopan AP), diethylamino hydroxybenzoyl hexyl benzoate (Uvinul A Plus), ecamsule (Mexoryl SX), methyl anthranilate, 4-aminobenzoic acid (PABA), cinoxate, ethylhexyl triazone (Uvinul T150), homosalate, 4-methylbenzylidene camphor (Parsol 5000), octyl methoxycinnamate (Octinoxate), octyl salicylate (Octisalate), padimate O (Escalol 507), phenylbenzimidazole sulfonic acid (Ensulizole), polysilicone-15 (Parsol SLX), trolamine salicylate, bemotrizinol (Tinosorb S), benzophenones 1-12, dioxybenzone, droxmetrizole trisiloxane (Mexoryl XL), isoctrizinol (Uvasorb HEB), octocrylene, oxybenzone (Eusolex 4360), sulisobenzone, bisoctrizole (Tinosorb M), titanium dioxide, zinc oxide, carotenoids, free radical scavengers, spin traps, retinoids and retinoid precursors such as retinol, retinoic acid and retinyl palmitate, ceramides, polyunsaturated fatty acids, essential fatty acids, enzymes, enzyme inhibitors, minerals, hormones such as estrogen, steroids such as hydrocortisone, 2-dimethylaminoethanol, copper salts such as copper chloride, Cu:Gly-His-Lys, peptides, sugar amines, coenzyme Q10, amino acids such as proline, vitamins, lactobionic acid, acetyl coenzyme A, niacin, riboflavin, thiamine, ribose, electron carriers such as NADH and FADH2, and other plant extracts such as oat, aloe vera, white chrysanthemum, soybean, shiitake mushroom extracts, and derivatives and mixtures thereof.

[0112] In one embodiment, the composition of the present invention is a skin care composition comprising a plant or bacterial extract described herein and at least one skin whitening active agent. Examples of suitable skin whitening active agents include, but are not limited to, tyrosinase inhibitors, melanin inhibitors, melanosome migration inhibitors including PAR-2 antagonists, peeling agents, sunscreens, retinoids, antioxidants, tranexamic acid, skin bleaching agents, allantoin, opacifying agents, talc and silica, zinc salts, and other agents described in Solano et al., Pigment Cell Res. 2006, 19(550-571). Examples of suitable tyrosinase inhibitors include, but are not limited to, vitamin C and its derivatives, vitamin E and its derivatives, kojic acid, arbutin, resorcinol, hydroquinone, flavones (e.g., licorice flavonoids, licorice root extract, mulberry root extract, Dioscorea Coposita root extract, saxifragaceae extract, etc.), ellagic acid, salicylates and derivatives, glucosamine and derivatives, fullerenes, hinokitiol, diacids, acetylglucosamine, magnolignan, combinations of two or more of these, and the like. Examples of vitamin C derivatives include, but are not limited to, ascorbic acid and its salts, ascorbic acid-2-glucoside, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, and natural extracts enriched with vitamin C. Examples of vitamin E derivatives include, but are not limited to, α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, and mixtures thereof, tocopherol acetate, tocopherol phosphate, and natural extracts enriched with vitamin E derivatives.Examples of resorcinol derivatives include resorcinol, 4-substituted resorcinols, such as 4-butylresorcinol (lucinol), 4-hexylresorcinol, phenylethylresorcinol, 4-alkylresorcinols such as 1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)-propane, and natural extracts rich in resorcinol, but are not limited thereto. Examples of salicylates include salicylic acid, acetylsalicylic acid, 4-methoxysalicyl acid and salts thereof, but are not limited thereto. In certain embodiments, the tyrosinase inhibitor is a 4-substituted resorcinol, a vitamin C derivative, or a vitamin E derivative. In yet another embodiment, the tyrosinase inhibitor comprises phenylethylresorcinol, 4-hexylresorcinol, or ascorbyl-2-glucoside.

[0113] Examples of suitable melanin-degrading agents include peroxides and enzymes (e.g., peroxidase and ligninase), but are not limited thereto. In certain embodiments, the melanin inhibitor is a peroxide and ligninase.

[0114] Examples of suitable melanosome transfer inhibitors include PAR-2 antagonists (e.g., soybean trypsin inhibitor or Bowman-Birk inhibitor), vitamin B3 and derivatives (e.g., niacinamide), essential soybeans, whole soybeans, soybean extracts. In certain embodiments, the melanosome transfer inhibitor is a soybean extract or niacinamide.

[0115] Examples of exfoliants include α-hydroxy acids (e.g., lactic acid, glycolic acid, malic acid, tartaric acid, citric acid, or any combination of the foregoing), β-hydroxy acids (e.g., salicylic acid, polyhydroxy acids, such as lactobionic acid and gluconic acid), and mechanical exfoliants (e.g., microdermabrasion), but are not limited thereto. In certain embodiments, the exfoliant is glycolic acid or salicylic acid.

[0116] Examples of sunscreens include, but are not limited to, avobenzone (Parsol 1789), bisdisulizole disodium (Neo Heliopan AP), diethylamino hydroxybenzoyl hexyl benzoate (Uvinul A Plus), ecamsule (Mexoryl SX), methyl anthranilate, 4-aminobenzoic acid (PABA), cinoxate, ethylhexyl triazone (Uvinul T150), homosalate, 4-methylbenzylidene camphor (Parsol 5000), octyl methoxycinnamate (Octinoxate), octyl salicylate (Octisalate), padimate O (Escalol 507), phenylbenzimidazole sulfonic acid (Ensulizole), polysilicone-15 (Parsol SLX), trolamine salicylate, bemotrizinol (Tinosorb S), benzophenones 1-12, dioxybenzone, droxmetrizole trisiloxane (Mexoryl XL), iscotrizinol (Uvasorb HEB), octocrylene, oxybenzone (Eusolex 4360), sulisobenzone, bisoctrizole (Tinosorb M), titanium dioxide, zinc oxide, and the like.

[0117] Examples of retinoids include, but are not limited to, retinol, retinaldehyde, retinoic acid, retinyl palmitate, isotretinoin, tazarotene, bexarotene, and adapalene. In certain embodiments, the retinoid is retinol.

[0118] Examples of antioxidants include water-soluble antioxidants such as sulfhydryl compounds and their derivatives (e.g., sodium metabisulfite and N-acetyl-cysteine, glutathione), lipoic acid and dihydrolipoic acid, stilbenoids (e.g., resveratrol and derivatives), lactoferrin, and ascorbic acid and ascorbic acid derivatives (e.g., ascorbyl-2-glucoside, ascorbyl palmitate, and ascorbyl polypeptide), but are not limited thereto. Examples of oil-soluble antioxidants suitable for use in the compositions of the present invention include butylated hydroxytoluene, retinoids (e.g., retinol and retinyl palmitate), tocopherols (e.g., tocopherol acetate), tocotrienols, and ubiquinone, but are not limited thereto. Examples of natural extracts containing antioxidants suitable for use in the compositions of the present invention include extracts containing flavonoids and isoflavonoids, and their derivatives (e.g., genistein and daidzein), extracts containing resveratrol, etc., but are not limited thereto. Examples of such natural extracts include grape seeds, green tea, pine bark, white mulberry, white mulberry without parthenolide, oat extract, grapefruit extract, wheat germ extract, hesperidin, grape extract, siberian cocklebur extract, licocalcon, chalcone, 2,2'-dihydroxychalcone, primrose extract, propolis, etc.

[0119] Examples of vitamins include vitamin A, vitamin B group (e.g., vitamin B3, vitamin B5, and vitamin B12), vitamin C, vitamin K, and vitamin E, and derivatives, but are not limited thereto.

[0120] The additional cosmetic active agent may be present in the composition in any suitable amount, e.g., amounts from about 0.0001 wt% to about 20 wt% of the composition, e.g., from about 0.001 wt% to about 10 wt%, e.g., from about 0.01 wt% to about 5 wt%, etc. In certain embodiments, it is in an amount of 0.1% - 5%, and in another embodiment, it is in an amount of 1% - 2%.

[0121] Various other materials may be present in the compositions of the present invention. These include, for example, chelating agents, humectants, proteins, opacifiers, conditioners, preservatives, fragrances, and the like. The compositions may include surfactants selected from the group consisting of, for example, anionic, nonionic, amphoteric, cationic, or combinations of two or more thereof.

[0122] Compositions and products containing such compositions of the present invention can be prepared using methods well known to those skilled in the art.

[0123] In certain embodiments, the present invention includes applying a compound or composition of the present invention via a substrate that includes such materials. Any suitable substrate can be used in the present invention. Examples of suitable substrates and substrate materials are disclosed, for example, in U.S. Patent No. 7,452,547 and U.S. Patent Application Publication No. 2009 / 0241242, which are hereby incorporated by reference in their entirety.

[0124] In one embodiment, the substrate is a wipe or a facial mask. Such embodiments include a water-soluble substrate as defined in the references cited above. In certain embodiments, the water-soluble substrate can have a size and shape such that covering the face of a human user facilitates placement of the water-soluble substrate as a mask substrate around the user's face. For example, the water-soluble mask substrate can have openings for the user's mouth, nose, and / or both eyes. Alternatively, the water-soluble substrate need not have such openings. Such a configuration without openings can be useful in embodiments of the present invention where the water-soluble substrate is placed to cover portions of the skin other than the face, or in cases where the water-soluble substrate is intended to be used as a wipe. The water-soluble substrate can have various shapes, such as a square shape (e.g., rectangular), or an arcuate shape such as circular or oval.

[0125] In one embodiment, the product comprises a plurality of water-soluble substrates of various shapes. In one embodiment of the present invention, the product comprises a first water-insoluble substrate and a second water-insoluble substrate. The first water-insoluble substrate is shaped to be applied to the forehead, and the second water-insoluble substrate is shaped to be applied in the vicinity of the mouth, such as in the regions above and / or below the lips, jaw, and / or cheeks. In one embodiment of the present invention, the first water-insoluble substrate is also applied to the nasal region of the face. The first water-insoluble substrate has a surface area of about 100 cm 2 ~ about 200 cm 2 , for example about 120 cm 2 ~ about 160 cm 2 and may have a surface area of, and the second water-insoluble substrate has a surface area of about 100 cm 2 ~ about 300 cm 2 , for example about 150 cm 2 ~ about 250 cm 2 . In one embodiment, the water-insoluble substrate is low in rigidity so that it can easily cover or conform to the user's face or other body parts, for example.

[0126] The present invention may include application to any skin that requires treatment in the human body. For example, it may be applied to any one or more of the skin of the face, neck, chest, back, arms, armpits, hands, and / or feet. In certain embodiments, the method includes applying a plant or bacterial extract described herein to the skin of the face.

[0127] Furthermore, the composition can be applied to other tissues including hair, nails, oral mucosa, nasal mucosa, or vaginal mucosa.

[0128] Any suitable method of applying the composition to the tissue in need can be used in accordance with the present invention. For example, the composition may be applied directly from the package to the skin in need, applied by hand to the tissue in need, or transferred from a substrate such as a wipe or mask, or may be a combination of two or more of these. In another embodiment, the composition may be applied via a dropper, tube, roller, spray, patch, or may be added to a bath or otherwise to water for application to tissues and the like.

[0129] In certain embodiments, the method of the present invention further comprises contacting the composition with the tissue over a period of time. For example, the composition may be contacted with the tissue for about 15 minutes or more. In another embodiment, the composition is contacted with the tissue for about 20 minutes or more, more preferably about 1 hour or more.

[0130] In certain embodiments, the method of the present invention includes a regimen that involves applying the composition to the tissue multiple times over a selected period.

[0131] For example, the present invention provides a method for treating signs of skin aging that includes applying a composition comprising the extract described herein to skin in need of treatment for signs of skin aging once or twice a day for at least 12 weeks, preferably at least 8 weeks, more preferably at least 2 weeks.

[0132] In certain embodiments, the method of the present invention includes applying to the tissue at least two different compositions or products comprising a plant or bacterial extract. For example, the method can include applying a first composition comprising the extract to the tissue in need of treatment, followed by applying a second composition comprising the same or a different extract to the skin in need of treatment. In certain embodiments, the first and second compositions can be independently selected from the group consisting of lotions, cleansers, masks, wipes, creams, serums, gels, and the like. In certain embodiments, at least one of the first and second compositions is a cleanser, lotion, cream, essence, or serum, and the other is a facial mask or wipe. In certain other embodiments, at least one of the first and second compositions is a cleanser, and the other is a lotion or cream.

[0133] In certain other embodiments, the method includes applying to the tissue in need of treatment at least three products or compositions comprising the extract. Preferably, such three products are selected from the group consisting of cleansers, lotions, creams, essences, and face masks.

[0134] The composition of the present invention can also be formulated into an ingestible composition. As used herein, "ingestible composition" means a composition intended to be ingested or administered orally. Examples of forms of ingestible compositions include, but are not limited to, tablets, pills, capsules, powders, granules, solutions or suspensions, and drip medications. Such compositions may be swallowed whole or may be in a chewable form. "Ingestible composition" may also be in the form of confectionery or food products such as cookies, candies, food bars, chewing gums, yogurt additives, sprinkles, tea, juice or other beverages, liquid shakes, etc. The ingestible composition does not include compositions intended to be topically administered to the skin or oral / vaginal cavity.

[0135] The composition can be used to treat various skin diseases and conditions, such as reducing the appearance of skin aging, skin inflammation, and skin pigmentation.

[0136] Examples of skin aging that can be treated by topical or oral use of the composition of the present invention include, but are not limited to, skin wrinkles, skin firmness or loss of elasticity, sagging, slackening, and loose tissues. As used herein, the term "wrinkle" includes fine wrinkles, fine lines, coarse wrinkles, cellulite, scars, and stretch marks. Examples of wrinkles include fine crow's feet around the eyes (e.g., "outer corner wrinkles"), forehead and cheek wrinkles, glabellar lines, and laugh lines around the mouth, but are not limited thereto.

[0137] Examples of skin inflammations that can be treated by topical or oral use of the composition of the present invention include, but are not limited to, arthritis, contact dermatitis, atopic dermatitis, psoriasis, seborrheic dermatitis, eczema, allergic dermatitis, polymorphic light eruption, inflammatory skin diseases, folliculitis, alopecia, urushi dermatitis, insect bites, irritation induced by external factors including, but not limited to, chemicals, trauma, contaminants (e.g., tobacco smoke), and exposure to UV or wind, and secondary conditions resulting from inflammation including, but not limited to, xerosis, seborrhea, pruritus, post-inflammatory hyperpigmentation, and scars.

[0138] Examples of skin pigmentations that can be treated by topical or oral use of the composition of the present invention include, but are not limited to, hyperpigmentation of the skin, light areas of the skin, uneven skin tone, discoloration and swelling around the eyes. Discoloration and swelling around the eyes include, but are not limited to, dark circles and puffiness under the eyes. In one embodiment, the dark circles under the eyes to be treated are the result of increased blood concentration in the skin under the eyes.

[0139] Examples of topical use of the composition containing the plant or bacterial extract and a cosmetically acceptable carrier described herein include, for example, skin aging of human skin, dry skin, pigment defects, UV damage on the skin, wrinkles, fine lines, rough skin, or unevenness of the skin such as crater skin, and diseases related to skin aging such as defective keratinization, acne, eczema, inflammation, and skin atrophy.

[0140] As used herein, "topical use" or "topically applied" means applying or spreading directly on the skin, hair, or nails, for example, by using an applicator such as a hand or a wipe.

[0141] In one embodiment, the present invention is a method for treating signs of skin aging, which includes topically applying a safe and effective amount of the composition containing the extract described herein to the skin in need of treatment for skin aging.

[0142] In another embodiment, the present invention is a method for improving skin barrier properties, which includes topically applying to skin that requires improvement in skin barrier function and moisturization, a composition containing the extract described herein.

[0143] In another embodiment, the present invention is a method for treating acne, which includes topically applying to skin that requires treatment of acne, a composition containing the extract described herein.

Examples

[0144] The following materials and test methods were used in the examples.

[0145] Gene expression test method Abdominal skin samples were obtained from human adults undergoing abdominoplasty. Informed consent was obtained from each patient, and all experimental procedures were approved by an Institutional Review Board (IRB). Subcutaneous fat was carefully removed, and 0.93 cm 2 skin biopsies were prepared under sterile conditions and acclimated overnight in DMEM / F12 (1:1) medium, 2% heat-inactivated fetal bovine serum, 10 μg / mL insulin, 10 ng / mL hydrocortisone, 10 ng / mL EGF, 1x ABAM, in a 5% CO2 humidified atmosphere. Skin explants were topically treated at various concentrations for 48 hours. At the end of the 48-hour incubation, half of the skin biopsy was lysed in 400 μL of lysis buffer containing 100 parts of RLT buffer (RNeasy Mini Kit, Qiagen, Valencia, CA) to 1 part of 2-mercaptoethanol, in a reinforced tube with a screw cap and O-ring closure, and the tissue was pulverized with ceramic beads (trademark PRECELLYS CKMix50-R, sold by Bertin Corp, Rockville, MD) in the tube. The tube was shaken at 6300 rpm for 40 seconds. RNA was extracted from the solution using the RNeasy Mini Kit (Qiagen, Valencia, CA) according to the manufacturer's instructions, and the RNA was eluted in 25 μL of RNase-free water.

[0146] Reverse transcription (RT) was performed using the Applied Biosystems High Capacity Reverse Transcription Kit (ThermoFisher Scientific, Bridgewater, NJ). Gene expression assays sold under the trade name TAQMAN and master mix sold under the trade name TAQMAN for cellular retinoic acid-binding protein 2 (CRABP2), heparin-binding epidermal growth factor (HbEGF), hyaluronic acid synthase 3 (HAS3), UDP-glucose ceramide glucosyltransferase (UGCG), and polymerase (RNA) II polypeptide A (POLR2A) were purchased from ThermoFisher Scientific (Bridgewater, NJ). qPCR analysis was performed using TaqMan® Master Mix (ThermoFisher Scientific, Bridgewater, NJ) and run on a real-time PCR system sold under the trade name QUANTSTUDIO 7 Flex System (ThermoFisher Scientific, Bridgewater, NJ). The expression of these genes was normalized to the expression of the human POLR2A housekeeping gene. Fold changes were calculated relative to untreated or vehicle controls, and a two-sided two-sample Student's t-test (Microsoft Office Excel 2007; Microsoft, Redmond, WA, USA) was performed.

[0147] RARg Transactivation Assay Method Retinoic acid receptor γ (RARg) agonism was evaluated using the Invitrogen GeneBLAzer RAR γ-UAS-bla HEK 293T cell line assay, in which activation of RARg results in the transcription of β-lactamase. When the FRET probe is added to the cells, FRET is observed. However, receptor activation and subsequent β-lactamase expression cleave the probe, and FRET is no longer observed.

[0148] Wash the cells in culture with PBS, trypsinize them, resuspend them in growth medium, count them using a ViCell cell counter, then spin down an appropriate amount of cells and resuspend them in assay buffer (0.5E6 cells / ml). Plate 15k cells in 30 ul of assay buffer into Greiner black wall, clear bottom plates using a Combi dispenser. Fill the last two columns with assay buffer. Add 10 ul of 4x concentrated test sample to the cells using a Janus dispenser, spin down the cells at 800 rpm for 2 minutes without braking, leave them at room temperature for 15 minutes, and incubate o / n at 37 °C.

[0149] After 18 - 20 hours of incubation, add 8 ul of FRET dye (Invitrogen K1096) using a Tempest dispenser, then spin down the plate at 800 rpm for 2 minutes without braking and incubate in the dark at room temperature for 2 hours. Clean the bottom of the plate using an anti-static cleaning wipe and measure fluorescence using a BMG Pherastar plate reader (using the FRET module, 10 readings, gain for both channels = 1000, Ex 409, Em1 460, Em2 530). The average Em1 and Em2 values from wells with assay buffer only are subtracted from the test Em1 and Em2 values respectively, and the subsequent determination of the Em1 / Em2 ratio represents the RARg activity. DMSO and ATRA are used as neutral and agonist controls respectively for normalization.

[0150] Extract of Acronictia acidula (E1) Pre-weighed frozen fruits of Acronicta acida were homogenized in a blender for 30 seconds with an equal amount of denatured alcohol added to the frozen fruits. Then, the pulp was mixed and stirred at ambient temperature (22 - 26 °C) for an additional 24 hours. Additional denatured alcohol was added as needed to maintain the pulp fully covered with alcohol. The mixture was then gravity filtered, and the filter cake was washed with a further amount of denatured alcohol. Next, the entire filtrate was dried under reduced pressure to remove the alcohol. The residue was lyophilized to obtain a dry substance free of extraction solvent and water. The extraction was repeated several times on the filter cake, and a 5 - 7% extraction yield was obtained regularly from each extract. One such batch was prepared using 100 kg of frozen fruits of Acronicta acida, and the dry extract (E1) was used in the subsequent experiments described herein.

[0151] Extracts (E2, E3) of Riccardia bischleriana Two extracts of Riccardia bischleriana were obtained from the Baruch S. Blumerg Institute, Doylestown, PA (formerly IVHR). The first extract was derived from the xylem of the plant (E2), and the second extract was derived from the roots of the plant (E3). Within the nomenclature of the IHVR collection, the extracts were labeled as IHVR_40256_G10 = X - 005348 - 001E002 and IHVR_40256_E10 = X - 005346 - 001M002, respectively. The xylem and roots of Riccardia bischleriana (Mez) Kosterm were collected from Guyana. 504.3 g of dried and ground xylem plant material was extracted with sufficient methanol, which was dried in vacuo to obtain 10.54 g of a crude methanol extract (E2) for X - 005348 - 001E002. 403.8 g of dried and ground root material was extracted with sufficient methanol, which was dried under vacuum to obtain 18.11 g of a crude methanol extract (E3) for X - 005346 - 001M002.

[0152] Extract (E4) of Actinomyces sp. A5640 The general culture and extraction methods of this strain are recorded at the Baruch S. Blumerg Institute, Doylestown, PA (formerly IVHR). Within the scope of the IHVR collection nomenclature, the extract is labeled as IHVR_39565_F7. The extract of Actinomyces species A5640 is referred to as E4 in this specification.

[0153] Extracts of Caltha palustris (E5) and Trollius chinensis (E6) Extracts of Caltha palustris (E5) and Trollius chinensis (E6) are available from Caithness Biotechnologies Ltd, UK (http: / / www.caithnessbiotechnes.com). These extracts are part of the Phytotitre Natural Product Library, which is available for purchase by anyone. The method for preparing the extracts is described by Caithness Biotechnologies Ltd. as non-polar using a mixture of methanol and methylene chloride. In a typical extraction, a pre-weighed dry powder biomass is suspended in a mixture of methanol / methylene chloride (1:1) and stirred overnight at ambient temperature. The suspension is then filtered and the filtrate is dried under reduced pressure to give a solvent-free residue. The residue is then dissolved in a sufficient amount of 100% DMSO to obtain a stock solution at a concentration of 10 mg / mL. Such a stock solution is used and diluted in an appropriate medium for screening.

[0154] (Example 1) Gene expression analysis of CRABP2 was performed with compositions of 0.1% (w / v) extract of Acronicta acida (E1), 0.1% (w / v) extract of Ricaria bernicosa (E2 and E3), and 0.1% (w / v) extract of Actinomyces sp. A5640 (E4) in 30 / 70 (v / v) polypropylene glycol / ethanol vehicle, respectively. Gene expression was carried out according to the above gene expression analysis test method. The test compositions were compared with a 0.1% retinol product sold under the trade name NEUTROGENA RAPID WRINKLE REPAIR (RWR) (Johnson & Johnson Consumer Inc., Skillman NJ), untreated, and vehicle-treated. The results are shown in Table 1.

[0155] [Table 1]

[0156] Results: Cellular retinol-binding protein (CRABP) is a family of cytoplasmic binding proteins that have been shown to facilitate retinol uptake and prevent the spontaneous non-enzymatic isomerization and oxidation of retinol. CRABP2 (cellular retinoic acid-binding protein-II) message has been shown to be upregulated by treatment with retinol in human skin both in vivo and in vitro.

[0157] This example shows that topical treatment of human skin explants with compositions of 0.1% (w / v) extract of Acronicta acida, Ricaria bernicosa, and Actinomyces sp. A5640 induces retinol-like bioactivity as indicated by induction of the expression of the gene for CRABP2. Thus, upregulation of CRABP2 and related retinol-like activities indicates retinol-like related skin benefits such as improved skin appearance, including reducing fine lines and reducing signs of aging including wrinkles.

[0158] (Example 2) The gene expression analysis of CRABP2 was performed using a composition of 0.04% (w / v) to 3% (w / v) extract of Acronicta acida (E1) in 30 / 70 (v / v) polypropylene glycol / ethanol vehicle according to the above gene expression analysis test method. The test compositions were compared with a 0.1% retinol product sold under the trade name NEUTROGENA RAPID WRINKLE REPAIR (RWR) and vehicle treatment. The results are shown in Table 2.

[0159]

Table 2

[0160] Results: Cellular retinol-binding protein (CRABP) is a family of cytoplasmic binding proteins that have been shown to facilitate retinol uptake and prevent the spontaneous non-enzymatic isomerization and oxidation of retinol. CRABP2 (cellular retinoic acid-binding protein-II) message has been shown to be upregulated by treatment with retinol in human skin both in vivo and in vitro.

[0161] This example shows that topical treatment of human skin explants with a composition of 0.04% (w / v) to 3% (w / v) extract of Acronicta acida induced the expression of the retinoic acid gene CRABP2 in human skin explants when applied topically, p < 0.05. The extract of Acronicta acida elicits retinol-like bioactivity similar to the benchmark 0.1% RWR retinol used as a positive control for the assay, as shown by the induction of CRABP2 gene expression. * , p < 0.05. The extract of Acronicta acida elicits retinol-like bioactivity similar to the benchmark 0.1% RWR retinol used as a positive control for the assay, as shown by the induction of CRABP2 gene expression.

[0162] (Example 3) Gene expression analysis for HAS3, UGCG, and HbEGF was performed using a composition of 0.1% (w / v) extract of Acronicta acida (E1) in 30 / 70 (v / v) polypropylene glycol / ethanol vehicle according to the gene expression analysis test method described above. The test compositions were compared to a 0.1% retinol product sold under the trade name NEUTROGENA RAPID WRINKLE REPAIR (RWR), vehicle-treated, and untreated. The results are shown in Table 3.

[0163] This upregulation of gene activity indicates retinol-like related skin benefits such as improved skin appearance, including reducing fine lines, wrinkles, and other signs of aging. Upregulation of the UCGC gene increases glycosphingolipid formation, which enhances epidermal lipid production that strengthens the skin barrier.

[0164]

Table 3

[0165] Results: The genes for heparin-binding epidermal growth factor (HbEGF) and hyaluronan synthase 3 (HAS3) are also induced by retinol. HbEGF is known to improve skin thickness and plumpness and reverse skin thinning due to steroid treatment, and HAS3 is known to improve skin hydration. UGCG is an enzyme involved in human ceramide synthesis and is known to improve the skin barrier.

[0166] Example 3 shows that topical treatment of human skin explants with a composition of 0.1% (w / v) extract of Acronicta acida induced HAS3, HbEGF, and ceramide glucosyltransferase (UGCG) gene expression similar to that of RWR, 0.1% retinol in human skin explants when applied topically, p < 0.05. * , p < 0.05.

[0167] (Example 4) A 10 mm biopsy of human skin explants was topically treated for 7 days with either 30 / 70 (v / v) polypropylene glycol / ethanol vehicle alone or a composition of 1% (w / v) Acronicta acida extract (E1) in 30 / 70 (v / v) polypropylene glycol / ethanol vehicle to investigate the effect on elastin fiber formation. In addition, the human skin explants were also topically treated with a formulation containing 0.1% retinol as a positive control. Furthermore, a sample of human skin explants was left untreated as a negative control. After 7 days, the skin biopsies were fixed in 10% buffered formalin solution (Thermo Fisher Scientific, Hudson, NH), dehydrated, and then embedded in paraffin. Sections 5 micrometers thick were taken from each biopsy. The sections were stained with Luna stain (American HistoLabs, Gaithersburg, MD), and purple elastin fibers were recorded. Images of the skin explants were obtained using a Leitz microscope and a Leica camera (Leica, Allendale, NJ). Figure 1 shows images of skin explants including untreated, vehicle-treated, 1% Acronicta acida extract (E1)-treated, and 1% retinol-treated.

[0168] Results: In contrast to untreated human skin samples or skin samples topically treated with 30 / 70 (v / v) polypropylene glycol / ethanol vehicle alone, an increase in elastin fiber formation was observed in the epidermis-dermis region of human skin explants topically treated for 7 days with a composition of 1% (w / v) Acronicta acida extract (E1) in 30 / 70 (v / v) polypropylene glycol / ethanol vehicle, similar to that observed with the formulation containing 0.1% retinol used as the experimental positive control.

[0169] Increased elastin formation results in the production of skin that is stronger, more elastic, and less prone to the signs and symptoms of skin aging, such as the formation of wrinkles. An increase in the formation of elastin fibers is a known retinol-induced anti-aging skin effect related to an improved skin appearance, including reducing fine lines and reducing the signs of aging, including reducing wrinkles. Therefore, the increase in elastin fiber formation by Acronictia acidula extract is a retinol-like activity and exhibits retinol-like related skin benefits, such as reducing fine lines and reducing the signs of aging, including reducing wrinkles.

[0170] (Example 5) Biopsies of 10 mm of human skin explants were topically treated for 7 days with either 30 / 70 (v / v) polypropylene glycol / ethanol vehicle alone or a composition of 1% (w / v) Acronictia acidula extract (E1) in 30 / 70 (v / v) polypropylene glycol / ethanol vehicle to investigate the effect on elastin fiber formation. In addition, the human skin explants were also topically treated with a formulation containing 0.1% retinol as an experimental positive control for comparison purposes. Furthermore, samples of human skin explants were left untreated as an experimental negative control for comparison purposes. After 7 days, the skin biopsies were fixed in 10% buffered formalin solution (Thermo Fisher Scientific, Hudson, NH), dehydrated, and then embedded in paraffin. Sections 5 micrometers thick were taken from each biopsy. The sections were stained with Herovici stain (American HistoLabs, Gaithersburg, MD) to record blue procollagen. Images of the skin explants were obtained using a Leitz microscope and a Leica camera (Leica, Allendale, NJ). Figure 2 shows images of the skin explants, including untreated, vehicle-treated, 1% Acronictia acidula extract (E1)-treated, and 1% retinol-treated.

[0171] Results: In contrast to untreated human skin samples or skin samples topically treated with 30 / 70 (v / v) polypropylene glycol / ethanol vehicle alone, in the epidermis-dermis region of human skin explants topically treated for 7 days with a composition of 1% (w / v) Acronicta acida extract (E1) in 30 / 70 (v / v) polypropylene glycol / ethanol vehicle, an increase in procollagen formation was observed, similar to that observed with a formulation containing 0.1% retinol used as a positive experimental control.

[0172] The increase in procollagen formation results in the production of skin that is stronger, more elastic, and less prone to the signs and symptoms of skin aging such as the formation of wrinkles, with improved hydration and improved skin barrier function. The increase in procollagen formation is a known retinol-induced anti-aging skin effect related to an improved skin appearance, including reducing fine lines and reducing signs of aging including reducing wrinkles. Thus, the increase in procollagen formation by Acronicta acida extract is a retinol-like activity and exhibits retinol-like related skin benefits, including reducing fine lines and reducing signs of aging including reducing wrinkles.

[0173] (Example 6) Various extracts of Carthamus tinctorius (E5) and Artemisia princeps (E6) were tested using the RARg Transactivation Assay at a concentration of 50 μg / ml on two separate days, replicating on the first day for 2 days. Extracts providing less than 15% receptor activation were considered inactive. Extracts providing more than 25% receptor activation were active.

[0174] The results are shown in Table 4.

[0175]

Table 4

[0176] In particular, the non-polar extracts of the petals of Tagetes erecta and the leaves of Populus sieboldii were significant RARγ activators. In contrast, the other extracts from each of the two plants were found to be inactive when tested at a concentration of 50 μg / mL.

[0177] Subsequent dose-response experiments using the RARγ transactivation assay were performed on the two active extracts of E5 and E6, as well as the extract of Acronicta acida fruits (E1), the extract of the xylem of Riccardia bischoffii (E2), the extract of the roots of Riccardia bischoffii (E3), and the extract of Actinomyces bacteria (E4) in which RARγ activity was confirmed by the RARγ transactivation assay.

[0178] The results are shown in Table 5.

[0179]

Table 5

[0180] The effect of the extract on cell viability was evaluated, and no toxicity was observed.

[0181] (Example 7) Compound 3-(4-farnesyloxyphenyl)-propionic acid was tested using the following RARγ transactivation assay.

[0182] 3-(4-farnesyloxyphenyl)-propionic acid was manufactured by Organix Inc., Woburn, Massachusetts, USA company. According to the usual synthetic scheme, 100 mg of the compound with a purity of over 98% was obtained. Based on all spectroscopic data, the structural composition of 3-(4-farnesyloxyphenyl)-propionic acid was confirmed.

[0183] The compound was tested as a solution in DMSO at different concentrations to evaluate the EC50 value, and it was found to be 0.22 μg / mL.

[0184] (Example 8) The effect of 3-(4-farnesyloxyphenyl)-propionic acid on skin hyperkeratinization was tested as follows.

[0185] Human epidermal skin equivalents from MatTek Company (Ashland, MA, USA) were used. The skin equivalents were topically treated for 48 hours with 10% oleic acid (OA) without or containing 1 μM of 3-(4-farnesyloxyphenyl)-propionic acid in a trademarked MatTek medium (phenol red-free, hydrocortisone-free). The epidermal skin equivalents were harvested at the end of the treatment, fixed in 10% neutral buffered formalin solution (Thermo Fisher Scientific, Hudson, NH, USA), dehydrated, and embedded in paraffin. Tissue sections (5 μm thick) were cut and stained with hematoxylin-eosin. For each skin equivalent, three photographs per section were taken. ImagePro Plus (Media Cybernetics Inc., Rockville, MD, USA) was used to measure the thickness of the stratum corneum or epidermis. The thickness of the stratum corneum was expressed as % of the total epidermis (= thickness of the stratum corneum divided by the sum of the thicknesses of the stratum corneum and epidermis). The hyperkeratinization rate (%) was normalized by the thickness of the 10% OA-treated tissue. Statistical analysis was performed using a two-sided two-sample equal variance Student's t-test (Microsoft Office Excel 2007; Microsoft, Redmond, WA, USA).

[0186] The results are shown in Table 6.

[0187]

Table 6

[0188] The results indicate that 3-(4-farnesyloxyphenyl)-propionic acid significantly (p < 0.05) reduced oleic acid (OA)-induced hyperkeratinization in human epidermal skin equivalents.

[0189] Acne vulgaris is a disease of the pilosebaceous unit with a multifactorial etiology including hyperkeratinization. Excessive unsaturated free fatty acids in the sebum of acne subjects can contribute to the impairment of the skin barrier associated with an increase in the thickness of the follicular stratum corneum and the inflammation seen in acne. Oleic acid is known to be able to induce hyperkeratinization in human epidermal skin equivalents that mimic acne lesion histology (Li, 2017). Therefore, the composition according to the present invention containing 3-(4-farnesyloxyphenyl)-propionic acid can be advantageously used for treating acne and other conditions associated with hyperkeratinization.

[0190] [Embodiments] (1) A method for treating signs of skin aging, the method comprising topically applying to skin in need of treatment of signs of skin aging a composition comprising an extract selected from the group consisting of an extract of Acronychia acidula, an extract of Richea veronica, an extract of Crocus sativus, an extract of Cola acuminata, an extract of Actinomyces bacteria, and combinations thereof. (2) The method according to embodiment 1, wherein the extract is a polar extract of the fruit of Acronychia acidula. (3) The method according to embodiment 1, wherein the extract is a polar extract of the xylem of Richea veronica or the root of Richea veronica. (4) The method according to embodiment 1, wherein the extract is a non-polar extract of the petals of Crocus sativus. (5) The method according to embodiment 1, wherein the extract is a non-polar extract of the leaves of Cola acuminata.

[0191] (6) The method according to embodiment 1, wherein the extract constitutes more than 0% by weight and up to about 20% by weight of the composition. (7) The method according to embodiment 1, wherein the composition also comprises a cosmetically acceptable carrier. (8) The method according to embodiment 1, wherein the signs of skin aging are a decrease in the synthesis of collagen or elastin. (9) The method according to embodiment 1, wherein the composition comprises 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester. (10) A method for improving skin barrier properties, comprising topically applying to skin in need of improvement in skin barrier function and moisturization a composition comprising an extract selected from the group consisting of an extract of Acronicta acida, an extract of Rhus vernicosa, an extract of Calendula officinalis, an extract of Aucuba japonica, an extract of Actinomyces bacteria, and combinations thereof.

[0192] (11) The method according to embodiment 10, wherein the extract is a polar extract of the fruit of Acronicta acida. (12) The method according to embodiment 10, wherein the extract is a polar extract of the xylem of Rhus vernicosa or the root of Rhus vernicosa. (13) The method according to embodiment 10, wherein the extract is a non-polar extract of the petals of Calendula officinalis. (14) The method according to embodiment 10, wherein the extract is a non-polar extract of the leaves of Aucuba japonica. (15) The method according to embodiment 10, wherein the extract constitutes more than 0% by weight and up to about 20% by weight of the composition.

[0193] (16) The method according to embodiment 10, wherein the composition further comprises a cosmetically acceptable carrier. (17) The method according to embodiment 10, wherein the topical application increases the level of hyaluronic acid in the skin. (18) The method according to embodiment 10, wherein the composition comprises 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester. (19) A method for treating acne, comprising topically applying to skin in need of acne treatment a composition comprising an extract selected from the group consisting of an extract of Acronicta acida, an extract of Rhus vernicosa, an extract of Calendula officinalis, an extract of Aucuba japonica, an extract of Actinomyces bacteria, and combinations thereof. (20) The method according to embodiment 19, wherein the extract is a polar extract of the fruit of Acronicta acida.

[0194] (21) The method according to embodiment 19, wherein the extract is a polar extract of the xylem of Ricaria vernicosa or the root of Ricaria vernicosa. (22) The method according to embodiment 19, wherein the extract is a non-polar extract of the petals of Papaver rhoeas. (23) The method according to embodiment 19, wherein the extract is a non-polar extract of the leaves of Quercus mongolica. (24) The method according to embodiment 19, wherein the extract constitutes more than 0% by weight and up to about 20% by weight of the composition. (25) The method according to embodiment 19, wherein the composition further comprises a cosmetically acceptable carrier.

[0195] (26) The method according to embodiment 19, wherein the composition comprises 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester.

Claims

**Claim 1**: A method for activating RARγ, comprising topically applying to the skin a composition comprising 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester (excluding medical acts on humans). **Claim 2** The method according to claim 1, wherein 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester constitutes up to 20% by weight of the composition. **Claim 3** The method according to claim 1, wherein the composition also comprises a cosmetically acceptable carrier. **Claim 4** A composition comprising 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester, for use in the method according to any one of claims 1 to 3.

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