RU2833927C2 - Plant and bacterial extracts showing retinol-like activity - Google Patents

Abstract

FIELD: cosmetic industry.

SUBSTANCE: group of inventions relates to the cosmetic industry, specifically to methods of using compositions having retinol-like activity. Method for eliminating signs of skin aging, including topical application to skin in need of skin aging, composition containing 3-(4-farnesiloxyphenyl)-propionic acid and/or an ethyl ester thereof, wherein said 3-(4-farnesiloxyphenyl)-propionic acid and/or an ethyl ester thereof are synthesized or contained in a polar extract of Acronychia acidula fruits, characterized by that a sign of skin aging is a decrease in collagen or elastin synthesis, and the fact that the composition contains from more than zero to 4% by weight of 3-(4-farnesiloxyphenyl)-propionic acid and/or its ethyl ester in terms of the total weight of the composition. Method for improving the properties of the skin barrier, involving topical application of composition containing 3-(4-farnesiloxyphenyl)-propionic acid on the skin in need of improving the function of the skin barrier and moisturizing and/or an ethyl ester thereof, wherein said 3-(4-farnesiloxyphenyl)-propionic acid and/or an ethyl ester thereof are synthesized or contained in a polar extract of Acronychia acidula fruits, characterized by that the composition contains from more than zero and up to 4 % by weight of 3-(4-farnesiloxyphenyl)-propionic acid and/or its ethyl ester in terms of the total weight of the composition. Method of treating acne, comprising topical application to skin in need of acne treatment, composition containing 3-(4-farnesiloxyphenyl)-propionic acid and/or an ethyl ester thereof, wherein said 3-(4-farnesiloxyphenyl)-propionic acid and/or an ethyl ester thereof are synthesized or contained in a polar extract of Acronychia acidula fruits, characterized by that the composition contains from more than zero and up to 4% by weight of 3-(4-farnesiloxyphenyl)-propionic acid and/or its ethyl ester in terms of the total weight of the composition.

EFFECT: above-described methods are effective for elimination of signs of skin aging, improvement of skin barrier properties, treatment of acne due to retinol-like biological activity of the composition applied to skin.

13 cl, 2 dwg, 6 tbl, 8 ex

Description

FIELD OF APPLICATION OF THE INVENTION

The present invention relates to compositions having retinol-like activity and methods of using the compositions for treating human tissues, including skin, hair, nails, oral mucosa, nasal mucosa, vaginal mucosa, etc.

DESCRIPTION OF THE KNOWN PRIOR ART

Human skin is subject to certain aging processes, some of which are caused by internal processes (e.g. age-related aging) and some by exogenous factors (e.g. photoaging). In addition, temporary or even chronic skin changes may occur, such as acne, oily or dry skin, keratoses, rosacea, photosensitivity, inflammatory, erythematous and allergic or autoimmune reactions such as dermatosis and photodermatosis.

The consequences of the above mentioned aging processes can include thinning of the skin, weakening of the bond between the epidermis and dermis, and a reduction in the number of cells and the blood vessels that feed them. This often leads to the formation of fine lines and wrinkles, and pigmented defects may also appear.

Retinoids are used to treat skin pathologies caused by internal aging, exogenous factors or skin diseases. However, despite the beneficial effects of retinoids, their benefits are limited due to their irritating effect on the skin. These side effects may limit their use. All retinoids used in cosmetic products are synthetic in origin, and there is a great demand from users of cosmetic products for natural compounds with retinol-like activity and beneficial effects for skin treatment.

To date, the search for alternative or natural compounds to replace retinoids has achieved limited success in the treatment of skin pathologies associated with aging, such as skin atrophy, photoaging, and in reducing the appearance of wrinkles, fine lines, stretch marks or cellulite.

U.S. Patent No. 9,220,928 to Ecobiotics LTD. discloses compounds derived from plants of the genus Acronychia , including 3-(4-farnesyloxyphenyl)-propionic acid, for use as antioxidants, antibacterials, anthelmintics, anti-inflammatory agents, cancer chemopreventive agents, dietary supplements, and/or flavoring agents. The patent, however, does not disclose anti-aging properties associated with the compositions disclosed therein.

U.S. Patent Publication No. 2013/0259815, owned by Johnson & Johnson Consumer Companies, Inc., describes methods for lightening skin by applying to the skin certain aromatic compounds or plant extracts, including plants of the genus Acronychia , containing such compounds.

Applicants have discovered that certain extracts unexpectedly exhibit retinol-like bioactivity and/or other consumer-desirable properties for use on the skin and other human tissues, including plant extracts of plants of the genera Acronychia , Licaria, Calendula , and Trigonella , as well as extracts of bacteria of the genus Actinomyces . Such extracts can be applied to the skin to provide significant anti-aging, improved skin barrier and hydration, acne prevention, and other beneficial effects commonly associated with retinol. Such extracts can also be applied, for example, to the oral mucosa, nasal mucosa, and vaginal mucosa.

The present invention relates to extracts that exhibit retinol-like biological activity, for example , in the skin, including upregulation of retinol-responsive genes such as RARg, CRABP2, HbEGF, HAS3 and UGCG in human skin explant culture. The invention further relates to methods for eliminating signs of aging, improving skin barrier function and providing beneficial effects against acne with such plant or bacterial extracts.

SUMMARY OF THE INVENTION

The present invention relates to a method for eliminating signs of skin aging, comprising topical application to skin in need of eliminating signs of skin aging, of a composition containing an extract selected from the group consisting of Acronychia acidula extracts, Licaria vernicosa extracts, Calendula officinalis extracts, Trigonella foengraecum extracts, Actinomyces bacterial extracts and combinations thereof.

The invention also relates to a method for improving the properties of the skin barrier, comprising topical application to skin in need of improving the function of the skin barrier and moisturizing, of a composition containing an extract selected from the group consisting of Acronychia acidula extracts, Licaria vernicosa extracts, Calendula officinalis extracts, Trigonella foengraecum extracts, Actinomyces bacterial extracts and combinations thereof.

The invention further relates to a method for treating acne, comprising topical application to skin in need of acne treatment of a composition containing an extract selected from the group consisting of Acronychia acidula extracts, Licaria vernicosa extracts, Calendula officinalis extracts, Trigonella foengraecum extracts, Actinomyces bacterial extracts and combinations thereof.

The present invention relates to a method for eliminating signs of skin aging, comprising topical application to skin in need of eliminating signs of skin aging, of a composition containing an extract of Acronychia acidula .

The present invention also relates to a method for improving skin barrier properties comprising topical application to skin in need of improved skin barrier function and hydration of a composition containing an extract of Acronychia acidula .

Furthermore, the invention relates to a method for treating acne, comprising locally applying to skin in need of acne treatment a composition containing an extract of Acronychia acidula .

The present invention also relates to a method for eliminating signs of skin aging, comprising topical application to skin in need of eliminating signs of skin aging, of a composition containing an extract of Licaria vernicosa .

The present invention also relates to a method for improving skin barrier properties comprising topical application to skin in need of improved skin barrier function and hydration of a composition containing an extract of Licaria vernicosa .

Furthermore, the invention relates to a method for treating acne, comprising locally applying to skin in need of acne treatment a composition containing an extract of Licaria vernicosa .

The present invention also relates to a method for eliminating signs of skin aging, comprising topical application to skin in need of eliminating signs of skin aging, of a composition containing an extract of Calendula officinalis .

The present invention also relates to a method for improving skin barrier properties, comprising topical application to skin in need of improved skin barrier function and hydration, of a composition containing Calendula officinalis extract.

The invention also relates to a method for treating acne, comprising locally applying to skin in need of acne treatment a composition containing an extract of Calendula officinalis .

The present invention also relates to a method for eliminating signs of skin aging, comprising topical application to skin in need of eliminating signs of skin aging, of a composition containing an extract of Trigonella foenum-graecum .

The present invention also relates to a method for improving skin barrier properties comprising topical application to skin in need of improved skin barrier function and hydration of a composition containing Trigonella foenum-graecum extract.

Furthermore, the invention relates to a method for treating acne, comprising locally applying to skin in need of acne treatment a composition containing an extract of Trigonella fo-graecum .

The present invention also relates to a method for eliminating signs of skin aging, comprising topical application to skin in need of eliminating signs of skin aging, of a composition containing an extract of Actinomyces bacteria.

The present invention also relates to a method for improving skin barrier properties, comprising topical application to skin in need of improved skin barrier function and hydration, of a composition containing an extract of Actinomyces bacteria.

The invention further relates to a method for treating acne, comprising locally applying to skin in need of acne treatment a composition containing an extract of Actinomyces bacteria.

BRIEF DESCRIPTION OF GRAPHIC MATERIALS

Fig. 1 shows photographs of skin explants, including untreated and treated with vehicle, 1% Acronychia acidula extract (E1) and 0.1% retinol, as described in Example 4.

Fig. 2 shows photographs of skin explants, including untreated and treated with vehicle, 1% Acronychia acidula extract (E1) and 0.1% retinol, as shown in Example 5.

DETAILED DESCRIPTION OF THE INVENTION

It is believed that according to the description provided herein, one skilled in the art will be able to use this invention to its fullest extent. The following specific embodiments can be considered only as illustrative examples, which in no way limit the rest of the present description.

All technical and scientific terms used herein, unless otherwise defined, have the meaning commonly understood by one of ordinary skill in the art to which the invention pertains. In addition, all publications, patent applications, patents and other materials mentioned herein are incorporated herein by reference. In this document, all percentages are by weight/volume of the total composition, unless otherwise specified.

Terms

As used herein, a composition "substantially free" of an ingredient means a composition containing about 2% or less of the ingredient by weight based on the total weight of the composition. In one embodiment, a composition substantially free of an ingredient contains about 1% or less, preferably about 0.5% or less, more preferably about 0.1% or less, more preferably about 0.05% or less, more preferably about 0.01% or less of the ingredient by weight based on the total weight of the composition. In certain embodiments, a composition substantially free of an ingredient does not contain the ingredient, i.e., the ingredient is not present in the composition.

As used herein, the term "cosmetically acceptable" means that the ingredients to which the term refers are suitable for use in contact with tissues (e.g., skin or hair) without non-specific toxicity, incompatibility, instability, irritation, allergic reaction, etc. As will be understood by one skilled in the art, cosmetically acceptable salts are acidic/anionic or alkaline/cationic salts. Cosmetically acceptable salts from inorganic bases include, for example, sodium or potassium salts, etc. Cosmetically acceptable salts from organic bases include, for example, salts formed by reaction with primary, secondary or tertiary amines, etc.

As used herein, the term "cosmetic" refers to a substance or preparation that enhances appearance and maintains, restores, imparts, imitates or enhances physical attractiveness or produces an attractiveness or youthfulness effect, especially with respect to the appearance of tissue or skin.

As used herein, the term "safe and effective amount" means an amount sufficient to initiate the desired effect, but low enough to prevent serious side effects. A 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 particular compound, extract, ingredient, or composition used, the particular cosmetically acceptable carrier used, and the like.

As used herein, the term "treating" means alleviating, preventing, or reversing a condition, disease, or disorder, or at least a detectable symptom thereof. In one embodiment, the term "treating" refers to alleviating, preventing, or reversing at least one measurable physical parameter related to the condition, disease, or disorder being treated, not necessarily detectable in or by the patient receiving the treatment. In another embodiment, the term "treating" refers to inhibiting or slowing the progression of the condition, disease, or disorder - either physically, such as by stabilizing a detectable symptom, or physiologically, such as by stabilizing a physical parameter, or both. In another embodiment, the term "treating" refers to delaying the onset of the condition, disease, or disorder.

In certain embodiments, the composition of the invention is administered as a prophylactic measure. As used herein, the terms "prevention" or "prevention" refer to reducing the risk of developing a particular condition, disease, or disorder.

The compositions of the present invention are suitable for eliminating or preventing signs of skin aging. As used herein, the term "signs of skin aging" includes the presence of folds and wrinkles, loss of elasticity, uneven skin tone and blotchiness. In a particularly preferred embodiment, the sign of aging is the presence of folds, wrinkles and/or loss of elasticity.

As used herein, the term "wrinkle" refers to fine lines, fine wrinkles, or deep wrinkles. Examples of wrinkles include, but are not limited to, fine lines around the eyes (e.g., crow's feet), forehead and cheek wrinkles, frown lines, and fine lines around the mouth.

The compositions of the present invention are suitable for improving skin texture or increasing skin density.

As used herein, the term "skin texture improvement" refers to smoothing the surface of the skin to eliminate ridges or depressions on the surface of the skin.

As used herein, the term "increasing the strength of the skin" means increasing the strength or elasticity of the skin, preventing loss of strength or elasticity of the skin, or preventing or eliminating sagging, laxity, or flabby skin.

As used herein, the term "loss of elasticity" includes loss of elasticity or structural integrity of skin or tissue, including, but not limited to, sagging, laxity, and flabby tissue. Loss of elasticity or structural integrity of tissue may result from a number of factors, including, but not limited to, disease, aging, hormonal changes, mechanical trauma, environmental stress, or the application of products to the tissue, such as cosmetics or pharmaceuticals.

In this document, the term "uneven skin tone" refers to a skin condition associated with diffuse or patchy pigmentation that can be classified as hyperpigmentation, such as postinflammatory hyperpigmentation.

In this document, the term "maculation" refers to a skin condition associated with redness or erythema.

In this document, the term "age spots" refers to a skin condition associated with individual pigmentation, such as small areas of darker pigmentation that may form on the face and also on the hands.

Signs of skin aging also include the presence of decreased skin thickness and abnormal or decreased synthesis of collagen, glycosaminoglycans, proteoglycans, elastin or glycoproteins, including fibronectin. In one embodiment, the sign of aging is selected from abnormal or decreased synthesis of collagen, glycosaminoglycans, proteoglycans, elastin or glycoproteins, including fibronectin. In another embodiment, the sign of skin aging is decreased synthesis of collagen or elastin.

The compositions are also suitable for the treatment or prevention of acne. As used herein, the term "acne" refers to disorders resulting from the effects of hormones and other substances on the sebaceous glands and hair follicles, typically resulting in clogged pores and the formation of inflammatory or non-inflammatory skin lesions. In particular, this refers to blemishes, lesions or pimples, acne precursors, blackheads and/or comedones. As used herein, the term "acne precursor" refers to an inflamed follicle that is not visually detectable on the skin surface with the naked eye (e.g., as in the case of a lesion).

The compositions of the present invention are also suitable for the treatment or prevention of rosacea. As used herein, the term "rosacea" means skin with persistent erythema, with or without papules, pustules or nodules.

The compositions of the present invention are also suitable for treating skin in need of improving the skin barrier function and hydration. As used herein, the expression "skin in need of improving the skin barrier function and hydration" refers to skin that is characterized by, among other things, a lack of hydration, a lack of sebum secretion, the presence of cracks, dryness, itching, flaking, xeroderma, dehydration, a lack of elasticity, a lack of shine, dullness, or a lack of lipid content.

The compositions of the present invention are also suitable for increasing endogenous hyaluronic acid (HA) levels in the skin, providing improved hydration and appearance with respect to at least one sign of skin aging. Topical application of the composition can increase hyaluronic acid levels to values approaching those of young skin, thereby providing the structural framework of the skin necessary to reduce the signs of skin aging.

The compositions of the present invention are also suitable for reducing epidermal hyperkeratosis. Accordingly, the composition can be used to treat or prevent conditions characterized by hyperkeratosis, such as acne or warts.

The compositions are also suitable for the treatment or prevention of skin conditions such as lax skin syndrome (an elastin-related disease), sclerosis/scleroderma (a collagen-related disease), keratosis pilaris, cellulite, stretch marks, psoriasis, warts, Kaposi's sarcoma, and cutaneous T-cell lymphoma.

The compositions of the present invention are also suitable for use on the oral mucosa. The compositions can be applied to the oral mucosa in need of increased mucin induction, increased hyaluronic acid induction, improved barrier or improved tight contact.

The compositions are additionally suitable for the treatment or prevention of asthma, allergies and itching. For example, for these purposes, the compositions can be applied topically to the skin or intranasally to the nasal mucosa.

Plant extracts

The inventors unexpectedly discovered that plant extracts have retinol-like biological activity. The extracts are obtained from plants, including, for example, plants of the genera Acronychia , Licaria, Calendula and Trigonella.

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.

In one embodiment, the extract is obtained from Acronychia acidula . Common names for Acronychia acidula are lemon aspen, hard aspen, and lemon tree. Synonymous Latin names for Aconychia acidua are Jambolifera acidula and Acronychia superba.

To plants of the genusLicariainclude, for example,Licaria vernicosa, Licaria brittoniana, Licaria canella, Licaria cubensis, Licaria velutina and Licaria triandra. There are about 40 species of the genusLicaria, which are endemic to Central and South America.

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

There are 15-20 species of plants in the genus Calendula , such as Calendula officinalis . Known synonyms of Calendua officinalis include Calendula aurantiaca, Calendula eriocarpa, Calendula hydruntina, Calendula prolifera, Calendula × santamariae , and Caltha officinalis .

In one embodiment, the extract is obtained from Calendula officinalis . Common names for Calendula officinalis include marigold, red ochre, common calendula, and pot marigold.

Plants of the genus Trigonella include 36 known species, such as Trigonella foen-graecum, Trigonella balansae, Trigonella corniculata, Trigonella maritima, Trigonella spicata, Trigonella caerulea, Trigonella occulta, Trigonella polycerata, Trigonella Calliceras, and Trigonella Cretica. Trigonella foenum-graecum , or fenugreek, is the best known member of the genus Trigonella .

In one embodiment, the extract is obtained from Trigonella foenum-graecum . Common names for Trigonella foen-graecum include fenugreek, Greek hay, Greek clover, serradella, fenugreek, "hu lu ba", fenugreek, and Greek fenugreek.

Any of a variety of Acronychia , Licaria, Calendula or Trigonella extracts can be used. A single extract or a combination of extracts can be used.

The extract may be obtained from any part of the plant, such as, for example, fruits, seeds, bark, leaves, flowers, petals, roots and wood. In some embodiments, the extract is obtained from the fruits, wood, petals or leaves of the plant.

In one embodiment, the extract is obtained from the fruit of Acronychia acidula .

In another embodiment, the extract is obtained from the wood of Licaria vernicosa .

In a further embodiment, the extract is obtained from the root of Licaria vernicosa .

In another embodiment, the extract is obtained from the petals of Calendula officinalis .

In another embodiment, the extract is obtained from the leaves of Trigonella foen-graecum .

In some embodiments, the Acronychia and/or Licaria extracts used in the present invention comprise compounds of the following formula II:

Where:

R ₁ is selected from the group consisting of C ₁ -C ₂₀ alkyl, C ₂ -C ₂₀ alkenyl, C ₂ -C ₂₀ alkynyl and C ₃ -C ₈ cycloalkyl or aryl;

R ₂ is selected from the group consisting of hydrogen, hydroxyl, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₃ -C ₈ cycloalkyl or aryl, -OC ₁ -C ₆ alkyl, -OC ₂ -C ₆ alkenyl, -OC ₂ -C ₆ alkynyl, -OC ₃ -C ₈ cycloalkyl or aryl, thiol, -SC ₁ -C ₆ alkyl, -SC ₂ -C ₆ alkenyl, -SC ₂ -C ₆ alkynyl, -SC ₃ -C ₈ cycloalkyl or aryl, -NR ₄ C ₁ -C ₆ alkyl, -NR ₄ C ₂ -C ₆ alkenyl, -NR ₄ C ₂ -C ₆ alkynyl and -NR ₄ C ₃ -C ₈ cycloalkyl or aryla;

R ₃ is selected from -CO ₂ H, -CO ₂ R ₄ or an isosteric equivalent of a carboxyl group, wherein R ₄ is C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₃ -C ₈ cycloalkyl or aryl; and

Y represents -(CH ₂ -CH ₂ )-, -(CH═CH)- or -(C≡C)-;

or their cosmetically acceptable salt.

In some embodiments, the Acronychia and/or Licaria extracts used in the present invention comprise compounds of formula II:

Where:

R ₁ is selected from the group consisting of C ₅ -C ₁₆ alkyl, C ₅ -C ₁₆ alkenyl and C ₅ -C ₁₆ alkynyl, more preferably C ₅ -C ₁₆ alkenyl, including, for example, farnesyl;

R ₂ is selected from the group consisting of hydrogen, hydroxyl, -OC ₁ -C ₆ alkyl, -OC ₂ -C ₆ alkenyl, -OC ₂ -C ₆ alkynyl, -OC ₃ -C ₈ cycloalkyl, more preferably hydrogen, hydroxyl, -OC ₁ -C ₆ alkyl, even more preferably hydrogen or -OC ₁ -C ₃ alkyl;

R ₃ is selected from -CO ₂ H, -CO ₂ R ₄ , where R ₄ is C ₁ -C ₆ alkyl or an isosteric equivalent of a carboxyl group; and

Y represents -(CH ₂ -CH ₂ )- or -(CH═CH)-;

or their cosmetically acceptable salt.

In some embodiments, at least one compound of the above formula is present in the Acronychia and/or Licaria extract at a concentration that is equal to or greater than 1% (or about 1%) to about 20%, or optionally from about 7% (or about 7%) to about 10% (or about 10%), by weight of the Acronychia and/or Licaria extract.

In some embodiments, the compounds of the above formula are in the form of an acid or alkyl ester selected from (or selected from the group consisting of) 3-(4-farnesyloxyphenyl)-propionic acid, 3-(4-farnesyloxy-3-hydroxyphenyl)-propionic acid, 3-(4-farnesyloxy-3-methoxyphenyl)-propionic acid, alkyl esters thereof, in particular ethyl esters thereof, and combinations of two or more thereof.

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

In some embodiments, 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester are present in the Acronychia and/or Licaria extract at a concentration of at least 1% (or about 1%) to about 20%, or optionally from about 7% (or about 7%) to about 10% (or about 10%) by weight of the Acronychia and/or Licaria extract.

3-(4-Farnesyloxyphenyl)propionic acid and/or its ethyl ester can be synthesized using conventional organic synthesis methods.

Accordingly, in one embodiment, a composition comprising 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester is used. Such a composition can be used in any of the methods of the present invention. In certain embodiments, the composition can comprise from 1% (or about 1%) to about 20%, or optionally from about 7% (or about 7%) to about 10% (or about 10%) by weight of 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester, based on the total weight of the composition, or more.

Suitable extracts can be prepared using conventional methods including, but not limited to, direct extraction of the substance from the biomass by grinding, soaking, pressing, squeezing, crushing, centrifuging and/or processes such as cold filtration, agitation/distillation, microwave extraction, supercritical/subcritical _CO2 gas extraction with or without a polarity modifier, pressurized solvent extraction, accelerated solvent extraction, pressurized or normal pressure hot water extraction, surfactant pressurized hot water extraction, oil extraction, membrane extraction, Soxhlet extraction, gold finger distillation/extraction, and/or the methods disclosed in, for example, U.S. Patent Nos. 7,442,391, 7,473,435 and 7,537,791 issued to Integrated Botanical Technologies, LLC and incorporated herein by reference; etc., or by using other methods such as solvent extraction, etc.

In methods involving solvent extraction, any of a variety of solvents may be used, including polar solvents, non-polar solvents, or combinations of two or more thereof. Suitable polar solvents include polar inorganic solvents such as water and the like, polar organic solvents such as alcohols and corresponding organic acids, for example, C ₁ -C ₈ alcohols including methanol, ethanol, propanol, butanol, and the like, as well as organic acids including acetic acid, formic acid, propanoic acid, and the like, polyols and glycols including C ₁ -C ₈ polyols/glycols, and the like, as well as combinations of two or more thereof. Suitable non-polar solvents include non-polar organic solvents such as alkanes, including _C1 - _C8 alkanes, cycloalkanes, including _C1 - _C8 cycloalkanes, alkyl ethers, including _C1 - _C8 alkyl ethers, petroleum ethers, ketones, including _C1 - _C8 ketones, methylene chloride, ethyl acetate, xylene, toluene, chloroform, vegetable oil, mineral oil, and the like. In another embodiment, the extraction can be carried out using the non-polar solvents described above or by supercritical fluid extraction in the presence or absence of a polar modifier such as _C1 - _C8 alcohols, water, _C1 - _C8 polyols/glycols, or _C1 - _C8 organic acids.

In one embodiment, the extract comprises an extract of Acronychia acidula . In another embodiment, the extract of the invention comprises a combination of polar and non-polar extracts of Acronychia acidula fruits. In another embodiment, the extract of the present invention comprises alcoholic or glycolic extracts of Acronychia acidula fruits.

In one embodiment, the extract comprises an extract of Licaria vernicosa . In another embodiment, the extract of the present invention comprises a combination of polar and non-polar extracts of Licaria vernicosa wood or Licaria vernicosa root. In another embodiment, the extract of the present invention comprises alcoholic extracts of Licaria vernicosa wood or Licaria vernicosa root.

In another embodiment, the extract is a polar extract obtained using a polar solvent comprising water, _C1 - _C8 alcohols, _C1 - _C8 polyols, _C1 - _C8 glycols, or combinations of two or more thereof. In some embodiments, the extract is extracted using one or more _C1 - _C4 alcohols, C1 _{- C4} polyols, and/or _C1 - _C4 glycols. In some embodiments, the extract is prepared using a solvent comprising methanol, ethanol, or a combination thereof, in the presence or absence of water.

In another embodiment, the extract is a polar extract obtained from the fruits of Acronychia acidula using a combination of alcohol and water.

In another embodiment, the extract is a polar extract obtained from ground (i.e. reduced to small particles) Licaria vernicosa wood or ground Licaria vernicosa root using methanol.

In one embodiment, the extract comprises an extract of Calendula officinalis . In another embodiment, the extract of the present invention comprises a combination of polar and non-polar extracts of Calendula officinalis petals. In another embodiment, the extract of the present invention comprises a non-polar extract of Calendula officinalis petals.

In one embodiment, the extract comprises an extract of Trigonella foenum-graecum . In another embodiment, the extract of the present invention comprises a combination of polar and non-polar extracts of Trigonella folium leaves. In another embodiment, the extract of the present invention comprises a non-polar extract of Trigonella foenum-graecum leaves.

In another embodiment, the extract is a non-polar extract obtained using a non-polar solvent containing 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 ethers and/or chloroform.

In another embodiment, the extract is a non-polar extract obtained using hexanes, ethyl acetate, chloroform, or mixtures of two or more of them. In another embodiment, the extract is a non-polar extract obtained using ethyl acetate.

In one embodiment, plant extracts can be obtained by extracting cell cultures of various plants, including cell cultures of the genera Acronychia , Licaria, Calendula or Trigonella . The cell cultures that are extracted to obtain plant extracts for use in the present invention can be in any form, including cell cultures in the form of suspensions and the like.

Bacterial extracts

The inventors have unexpectedly discovered that bacterial extracts exhibit retinol-like biological activity. Bacteria of the genus Actinomyces include many fully characterized species as well as poorly characterized species, such as one species collected in the United States and labeled species A5640. A sample of these bacteria was collected, grown in culture, and converted to an extract. The extract is part of a natural product collection now controlled by the Baruch S. Blumerg Institute, Doylestown, Pennsylvania (formerly known as IHVR). In one embodiment, the extract is obtained from an Actinomyces species capable of producing a chemical composition similar to that obtained using extract A5640. In another embodiment, the bacteria are collected in the United States and the strain is identical to the previously isolated species A5640.

Compositions

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

The methods of the present invention preferably include applying a composition containing a safe and effective amount of an extract of the present invention to the tissue in need of treatment. In the case where the skin needs to eliminate signs of aging, an effective amount of such an extract can be used to slow down aging.

In one embodiment, the methods comprise applying to the fabric in need thereof from greater than zero to about 20% by weight of the extract based on the total weight of the composition. In another embodiment, the methods comprise applying to the fabric in need thereof from about 0.0001 to about 20% by weight, or from about 0.001 to about 10% by weight, or from about 0.01 to about 5% by weight, or from about 0.1 to about 5% by weight, or from about 0.2 to about 2% by weight of the extract based on the total weight of the composition. In yet another embodiment, the methods comprise applying to the fabric from greater than zero to about 1% by weight, or from about 0.0001 to about 1% by weight, or from about 0.001 to about 1% by weight, or from about 0.01 to about 1% by weight, based on the total weight of the composition.

Depending on the route of administration, i.e. topical, oral, buccal, intranasal, periodontal or vaginal administration, any suitable carrier may be used. Preferably, the carrier for the topical composition is a cosmetically acceptable carrier. As will be understood by one skilled in the art, cosmetically acceptable carriers include carriers that are suitable for use in contact with the body, such as skin, hair or nails, without undue toxicity, incompatibility, instability, irritation, allergic reaction, etc.

The compositions employ a safe and effective amount of carrier. For example, the carrier may comprise from about 50% to about 99.999%, preferably from about 80% to about 99.9%, more preferably from about 99.9% to about 95%, most preferably from about 99.8% to about 98% of the composition. The carrier may be present in a wide variety of forms. For example, emulsion carriers are utilized in the present invention, including, but not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone emulsions. These emulsions may have a wide range of viscosities, such as from about 100 cP to about 200,000 cP.

Examples of suitable cosmetically acceptable carriers include cosmetically acceptable solvents and substances for cosmetic solutions, suspensions, lotions, creams, serums, essences, gels, toners, lipsticks, sprays, ointments, liquid cleansers and soap bars, shampoos, hair conditioners, pastes, foams, mousses, powders, shaving creams, wipes, patches, strips, patches with a power source, microneedle patches, bandages, hydrogels, film-forming products, face and skin masks, decorative cosmetics, liquid drops, and the like. These types of products can cover several types of cosmetically acceptable carriers, including, but not limited to, solutions, suspensions, emulsions such as microemulsions and nanoemulsions, gels, solids, liposomes, products of other encapsulation technologies, etc. p.

Non-limiting examples of such carriers are provided below. Other carriers can be incorporated into the formulations by those of ordinary skill in the art. In one embodiment, the carrier comprises water. In a further embodiment, the carrier can also comprise one or more aqueous or organic solvents. Examples of organic solvents include, but are not limited to: dimethyl isosorbide; isopropyl myristate; cationic, anionic, and nonionic 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, but are not limited to, alkanols having from about 2 carbon atoms to about 12 carbon atoms (e.g., from about 2 carbon atoms to about 4 carbon atoms), such as isopropanol and ethanol. Examples of polyols include, but are not limited to, polyols having from about 2 carbon atoms to about 15 carbon atoms (e.g., from about 2 carbon atoms to about 10 carbon atoms), such as propylene glycol. Organic solvents may be present in the carrier in an amount, based on the total weight of the carrier, of from about 1 percent to about 99.99 percent (e.g., from about 20 percent to about 50 percent). Water may be present in the carrier (prior to use) in an amount, based on the total weight of the carrier, of from about 5 percent to about 95 percent (e.g., from about 50 percent to about 90 percent). The solutions may contain any suitable amount of solvent, including from about 40 to about 99.99%. In one embodiment, the solutions are 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 99%.

A lotion may be prepared from such a solution. Typically, in addition to the solvent, lotions contain at least one emollient. Lotions may contain from about 1% to about 20% (e.g., from about 5% to about 10%) of the emollient(s) and from about 50% to about 90% (e.g., from about 60% to about 80%) of water. As used herein, the term "emollients" refers to materials used to prevent or relieve dryness and to protect the skin or hair. Examples of emollients include, but are not limited to, those listed 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 referred to as the ICI Handbook).

Another type of product that can be made from a solution is a cream. Typically, a cream contains about 5% to about 50% (e.g., about 10% to about 20%) of the softener(s) and about 45% to about 85% (e.g., about 50% to about 75%) of water.

Another type of product that can be prepared from a solution is an ointment. An ointment may contain a simple base of animal, vegetable or synthetic oils or semi-solid hydrocarbons. An ointment may contain from about 2% to about 10% emollient(s) plus from about 0.1% to about 2% thickener(s).

The compositions useful in the present invention may also be formulated as emulsions. If the carrier is an emulsion, it contains from about 1% to about 10% (e.g., from about 2% to about 5%) of the emulsifier(s). The emulsifiers may be nonionic, anionic, or cationic. Examples of emulsifiers include, but are not limited to, those listed in the ICI Handbook, pp. 1673-1686.

Lotions and creams may be formulated as emulsions. Typically, such lotions contain from 0.5% to about 5% emulsifier(s), while such creams typically contain from about 1% to about 20% (e.g., about 5% to about 10%) emollient(s); from about 20% to about 80% (e.g., 30% to about 70%) water; and from about 1% to about 10% (e.g., about 2% to about 5%) emulsifier(s).

Skin care preparations based on a single-phase emulsion, such as lotions and creams, of the "oil in water" type and the "water in oil" type, are well known in the art and are used in the claimed invention. The claimed invention also uses compositions based on a multi-phase emulsion of the "water in oil in water" type or the "oil in water in oil" type. Typically, such single-phase or multi-phase emulsions contain water, emollients and emulsifiers as the main ingredients.

The compositions of the present invention can also be formulated as a gel (e.g., an aqueous, alcoholic, hydroalcoholic, or oil gel using suitable gelling agent(s)). Suitable gelling agents for aqueous and/or alcoholic gels include, but are not limited to, natural gums, acrylic acid and acrylate polymers and copolymers, cellulose derivatives (e.g., hydroxymethylcellulose and hydroxypropylcellulose). Suitable gelling agents for oils (such as mineral oil) include, but are not limited to, hydrogenated butylene/ethylene/styrene copolymer and hydrogenated ethylene/propylene/styrene copolymer. In such gels, the content of these gelling agents is typically from about 0.1% to 5% by weight.

The compositions of the present invention may also be formulated in solid form (e.g., a wax-based stick, a soap bar composition, a powder, or a wipe). The composition of the present invention may also be combined with a solid, semi-solid, or soluble substrate (e.g., a wipe, a mask, a pad, a glove, or a strip).

The compositions of the present invention may further comprise one or more additional cosmetically active agents. As used herein, the term "cosmetically active agent" means a compound that has a cosmetic or therapeutic effect on human tissues such as skin, hair, nails or mucous membranes. Examples of suitable additional cosmetically active agents include: skin lightening agents, darkening agents, anti-acne agents, gloss control agents, antimicrobial agents such as antiyeast agents, antifungal and antibacterial agents, anti-inflammatory agents, antiparasitic agents, external analgesics, sunscreens, photoprotectors, antioxidants, keratolytic agents, cleansers/surfactants, humectants, nutrients, vitamins, energy boosting agents, antiperspirants, astringents, deodorants, hair removers, hair growth enhancers, hair growth retardants, thickeners, hydration enhancers, performance enhancers, anti-callus agents, skin conditioning agents, anti-cellulite agents, fluorides, tooth whitening agents, antiplaque agents and plaque dissolving agents, stain control agents odor agents such as odor-masking agents or pH-altering agents, etc.

Examples of various suitable additional cosmetically acceptable active ingredients include hydroxy acids, benzoyl peroxide, D-panthenol, UV filters including but not limited to avobenzone (Parsol 1789), bisdisulisole disodium (Neo Heliopan AP), diethylaminohydroxybenzoylhexyl benzoate (Uvinul A Plus), ecamsule (Mexoryl SX), methyl anthranilate, 4-aminobenzoic acid (PABA), cinoxate, ethylhexyl triazone (Uvinul T 150), homosalate, 4-methylbenzylidene camphor (Parsol 5000), octyl methoxycinnamate (octinoxate), octyl salicylate (octisalate), padimate O (Escalol 507), phenylbenzimidazole sulfonic acid (ensulisole), polysilicon-15 (Parsol SLX), trolamine salicylate, bemotrizinol (Tinosorb S), benzophenones 1-12, dioxybenzone, drometrizole trisiloxane (Mexoryl XL), iscotrizinol (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 estrogens, steroids such as hydrocortisone, 2-dimethylaminoethanol, copper salts such as copper chloride, peptides containing copper such as Cu:Gly-His-Lys, dipeptides, 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 FADH ₂ , and other plant extracts such as oat extract, aloe vera, feverfew, soybean, shiitake mushroom, and their derivatives and mixtures.

In one embodiment, the compositions of the present invention are skin care compositions that comprise a plant or bacterial extract as described herein and at least one skin lightening active agent. Examples of suitable skin lightening active agents include, but are not limited to, tyrosinase inhibitors, melanin inhibiting agents, melanosome transfer inhibiting agents including PAR-2 antagonists, scrubs, sunscreens, retinoids, antioxidants, tranexamic acid, skin whitening agents, allantoin, opacifiers, talcs and silicas, zinc salts, and the like, and other agents as 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, resorcinols, hydroquinone, flavones such as licorice flavonoids, licorice root extract, mulberry root extract, Dioscorea Coposita root extract, saxifrage (Saxifraga) extract, and the like, ellagic acid, salicylates and derivatives, glucosamine and derivatives, fullerene, hinokitiol, dicarboxylic acid, acetylglucosamine, magnolignan, combinations of two or more thereof, 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 extract enriched with vitamin C. Examples of vitamin E derivatives include themselves, among others, alpha-tocopherol, beta-tocopherol, gamma-tocopherol, delta-tocopherol, alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, delta-tocotrienol and mixtures thereof, tocopherol acetate, tocopherol phosphate and natural extracts enriched with vitamin E derivatives. Examples of resorcinol derivatives include, among others, resorcinol, 4-substituted resorcinols such as 4-alkylresorcinols such as 4-butylresorcinol (rucinol), 4-hexylresorcinol, phenylethylresorcinol, 1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)propane and the like and natural extracts enriched with resorcinols. Examples of salicylates include, but are not limited to, salicylic acid, acetylsalicylic acid, 4-methoxysalicylic acid, and salts thereof. In some embodiments, tyrosinase inhibitors comprise 4-substituted resorcinol, a vitamin C derivative, or a vitamin E derivative. In another embodiment, the tyrosinase inhibitor comprises phenylethylresorcinol, 4-hexylresorcinol, or ascorbyl-2-glucoside.

Examples of suitable melanin degradation promoting agents include, but are not limited to, peroxides and enzymes such as peroxidases and ligninases. In some embodiments, the melanin inhibiting agents comprise a peroxide or ligninase.

Examples of suitable melanosome transfer inhibiting agents include PAR-2 antagonists such as soybean trypsin inhibitor or Bowman-Birk inhibitor, vitamin B3 and derivatives such as niacinamide, soybean essence, whole soybean, soybean extract. In some embodiments, the melanosome transfer inhibiting agents comprise soybean extract or niacinamide.

Examples of exfoliants include, but are not limited to, alpha hydroxy acids such as lactic acid, glycolic acid, malic acid, tartaric acid, citric acid, or any combination of any of the foregoing, beta hydroxy acids such as salicylic acid, polyhydroxy acids such as lactobionic acid and gluconic acid, and mechanical exfoliants such as microdermabrasion agents. In certain embodiments, the exfoliant comprises glycolic acid or salicylic acid.

Examples of sunscreens include, but are not limited to, avobenzone (Parsol 1789), bisdisulizole disodium (Neo Heliopan AP), diethylaminohydroxybenzoylhexyl benzoate (Uvinul A Plus), ecamsule (Mexoryl SX), methyl anthranilate, 4-aminobenzoic acid (PABA), cinoxate, ethylhexyl triazone (Uvinul T 150), 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, drometrizole trisiloxane (Mexoryl XL), iscotrizinol (Uvasorb HEB), octocrylene, oxybenzone (Eusolex 4360), sulisobenzone, bisoctrizol (Tinosorb M), titanium dioxide, zinc oxide, etc.

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.

Examples of antioxidants include, but are not limited to, water-soluble antioxidants such as sulfhydryl compounds and derivatives thereof (e.g., sodium metabisulfite and N-acetylcysteine, glutathione), lipoic acid and dihydrolipoic acid, stilbenoids such as resveratrol and derivatives, lactoferrin, and ascorbic acid and ascorbic acid derivatives (e.g., ascorbyl-2-glucoside, ascorbyl palmitate, and ascorbyl polypeptide). Fat-soluble antioxidants suitable for use in the compositions of the present invention include, but are not limited to, butylated hydroxytoluene, retinoids (e.g., retinol and retinyl palmitate), tocopherols (e.g., tocopherol acetate), tocotrienols, and ubiquinone. Natural extracts containing antioxidants suitable for use in the compositions of the present invention include, but are not limited to, extracts containing flavonoids and isoflavonoids and derivatives thereof (e.g., genistein and diadzein), extracts containing resveratrol, etc. Examples of such natural extracts include extracts of grape seeds, green tea, pine bark, feverfew, feverfew extract that does not contain parthenolide, oat extract, pomelo extract, wheat germ extract, hesperidin, grape extract, purslane extract, licochalcone, chalcone, 2,2'-dihydroxychalcone, primrose extract, propolis, etc.

Examples of vitamins include, but are not limited to, vitamin A, B vitamins (such as vitamin B3, vitamin B5, and vitamin B12), vitamin C, vitamin K, and vitamin E and their derivatives.

The additional cosmetically active agent may be present in the composition in any suitable amount, for example in an amount of from about 0.0001% to about 20% by weight of the composition, for example from about 0.001% to about 10%, in particular from about 0.01% to about 5%. In certain embodiments, in an amount of from 0.1% to 5%, and in other embodiments, from 1% to 2%.

A number of other substances may also be present in the compositions of the present invention. These include, for example, chelating agents, humectants, proteins, polypeptides, opacifiers, pigments, conditioning agents, preservatives, fragrances, etc. The compositions may include surfactants, for example, selected from the group consisting of anionic, nonionic, amphoteric, cationic surfactants, or a combination of two or more of these.

The composition and products containing such compositions of the present invention can be prepared using techniques well known to those of ordinary skill in the art.

In one embodiment, the present invention provides for applying a compound or composition of the present invention via a substrate comprising such a material. Any suitable substrate can be used in the present invention. Examples of suitable substrates and substrate materials are described, for example, in U.S. Patent No. 7,452,547 and U.S. Patent Application Publication No. 2009/0241242, the contents of which are incorporated herein by reference in their entirety.

In one embodiment, the substrate is a wipe or a face mask. Such embodiments comprise a water-insoluble substrate, particularly as defined in the references cited above. In certain embodiments, the water-insoluble substrate may be sized and shaped to cover the face of a human user to facilitate placement of the water-insoluble substrate on the user's face as a mask substrate. For example, the water-insoluble mask substrate may have openings for the mouth, nose, and/or eyes of the user. Alternatively, the water-insoluble mask substrate may not have such openings. Such a configuration without openings may be suitable for embodiments of the invention in which the water-insoluble substrate is intended to be wrapped around areas of skin not on the face, or the water-insoluble substrate is intended to be used as a wipe. The water-insoluble substrate may have various shapes, such as an angular shape (e.g., rectangular) or a curved shape, in particular round or oval.

In one embodiment, the product comprises a plurality of water-insoluble substrates of different shapes. In one embodiment, the product comprises a first water-insoluble substrate and a second water-insoluble substrate. The first water-insoluble substrate is shaped for application to the forehead, and the second water-insoluble substrate is shaped for application near the mouth, in particular to the areas above and/or below the lips, the chin and/or cheeks. In one embodiment, the first water-insoluble substrate is also applied to the nasal region of the face. The first water-insoluble substrate may have a surface area of about 100 cm ² to about 200 cm ² , in particular from about 120 cm ² to about 160 cm ² , and the second water-insoluble substrate has a surface area of about 100 cm ² to about 300 cm ² , in particular from about 150 cm ² to about 250 cm ² . In one embodiment, the water-insoluble substrate has low rigidity such that it can, for example, be easily wrapped around or conform to the shape of the user's face or other body parts.

The present invention may be applied to any area of skin on the human body in need of treatment. For example, it may be applied to one or more of the skin of the face, neck, chest, back, arms, armpits, hands and/or legs. In certain embodiments, the method includes applying a plant or bacterial extract as described herein to the skin of the face.

Moreover, the compositions can be applied to other tissues, including hair, nails, oral mucosa, nasal mucosa or vaginal mucosa.

In accordance with the present invention, any suitable method for applying the composition to the fabric in need thereof may be used. For example, the composition may be applied directly from the package to the fabric in need thereof, applied by hand to the fabric in need thereof, or transferred from a substrate such as a napkin or mask, or a combination of two or more of these may be used. In other embodiments, the composition may be applied by means of a pipette, tube, roller, spray, patch, or added to a bath or other water for application to the fabric, etc.

In certain embodiments, the methods of the present invention further comprise the step of bringing the composition into contact with the tissue for a period of time. For example, the composition is left in contact with the tissue for a period of time of about 15 minutes or more. In another embodiment, the composition is left in contact with the tissue for a period of about 20 minutes or more, more preferably about 1 hour or more.

In certain embodiments, the method of the present invention includes a regimen comprising repeatedly applying the composition to the fabric over a selected period of time.

For example, the invention provides a method for eliminating signs of aging, comprising applying to skin in need of eliminating signs of aging of the skin a composition containing the extract described herein, once or twice a day for at least 12 weeks, preferably at least 8 weeks, and more preferably at least 2 weeks.

In some embodiments, the methods of the present invention include applying to a fabric at least two different compositions or products comprising plant or bacterial extracts. For example, the methods may include applying to a fabric in need of treatment a first composition comprising an extract, followed by applying to skin in need of treatment a second composition comprising the same extract or a different extract. In certain embodiments, the first and second compositions may 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 other certain embodiments, at least one of the first and second compositions is a cleanser, and the other is a lotion or cream.

In some other embodiments, the method comprises applying at least three products or compositions containing the extract to the tissue in need of treatment. Such three products are preferably selected from the group consisting of cleansers, lotions, creams, essences and facial masks.

The compositions of the present invention may also be formulated as an internal composition. As used herein, the term "internal composition" means a composition that is intended to be ingested or taken orally. Examples of internal composition forms include, but are not limited to, tablets, pills, capsules, powders, granules, solutions or suspensions, and drops. Such compositions may be swallowed whole or may be chewable. An "internal composition" may also be in the form of a confectionery or food product, such as a cookie, candy, food bar, chewing gum, yogurt topping, sprinkles, tea, juice or other beverage, liquid cocktail, or the like. Internal compositions do not include compositions intended for topical application to the skin or oral/vaginal cavity.

The composition can be used to treat various skin diseases and conditions, in particular to reduce the appearance of signs of skin aging, skin inflammation and skin pigmentation.

Examples of signs of skin aging that can be improved by topical or oral application of the compositions of the present invention include, but are not limited to, wrinkles in the skin, loss of skin density or elasticity, sagging, laxity and looseness of the tissue. As used herein, the term "wrinkle" includes a fine line, fine wrinkles, coarse wrinkles, cellulite, scars and stretch marks. Examples of wrinkles include, but are not limited to, fine lines around the eyes (e.g., crow's feet), wrinkles on the forehead and cheeks, frown lines and expression lines around the mouth.

Examples of inflammatory skin conditions that can be treated by topical or oral administration of the compositions of the present invention include, but are not limited to, arthritis, contact dermatitis, atopic dermatitis, psoriasis, seborrheic dermatitis, eczema, allergic dermatitis, polymorphic mild eruption, inflammatory dermatoses, folliculitis, alopecia, poison ivy exposure, insect bites, irritation due to external factors including, but not limited to, chemicals, trauma, pollutants (such as cigarette smoke) and exposure to UV rays or wind, and secondary conditions associated with inflammation including, but not limited to, xerosis, hyperkeratosis, pruritus, post-inflammatory hyperpigmentation, scarring, etc.

Examples of skin pigmentation that can be treated by topical or oral application of the compositions of the present invention include, but are not limited to, hyperpigmentation of the skin, light areas of the skin, uneven skin tone, discoloration and puffiness around the eye. Discoloration and puffiness around the eye include, but are not limited to, dark circles and bags under the eye. In one embodiment, the dark circles under the eye that need to be eliminated are the result of increased blood concentration in the skin under the eye.

Topical application of the compositions containing the plant or bacterial extracts described herein and a cosmetically acceptable carrier includes, for example, aging human skin, dry skin, pigment defects, UV damage to the skin, skin irregularities such as wrinkles, fine lines, rough skin or skin with large pores, and diseases associated with aging skin such as disordered keratosis, acne, eczema, inflammation and skin atrophy.

As used herein, the terms "topical application" and "topical application" mean direct application or distribution to the skin, hair or nails, such as by hand or an applicator such as a wipe.

In one embodiment, the present invention is a method for improving signs of skin aging, comprising topically applying to skin in need of improving signs of skin aging a safe and effective amount of a composition containing an extract described herein.

In another embodiment, the present invention relates to a method for improving skin barrier properties comprising topically applying to skin in need of improved skin barrier function and hydration a composition comprising the extract described herein .

In another embodiment, the invention is a method of treating acne comprising topically applying to skin in need of treatment of acne a composition comprising an extract described herein .

EXAMPLES

The following test methods were used in the examples.

Method for testing gene expression

Abdominal skin samples were collected from adult subjects undergoing abdominoplasty. Informed consent was obtained from each patient and all experimental steps were approved by the institutional review board (IRB). Subcutaneous fat was carefully removed, 0.93 ^cm2 skin biopsies were obtained under sterile conditions and acclimatized in DMEM/F12 (1:1), 2% heat-inactivated fetal bovine serum, 10 μg/ml insulin, 10 ng/ml hydrocortisone, 10 ng/ml EGF, 1x ABAM in a humidified atmosphere containing 5% _CO2 overnight. Skin explants were treated topically with various concentrations for 48 hours. At the end of 48 h of incubation, half of the skin biopsies were lysed in 400 μl of lysis buffer consisting of 100 parts RLT buffer (RNeasy Mini Kit, Qiagen, Valencia, CA, USA) and one part 2-mercaptoethanol in a thick-walled tube with a screw cap and an O-ring, and ceramic tissue abrasion beads (marketed as PRECELLYS CKMix50-R, Bertin Corp, Rockville, MD, USA) were added to the tube. The tubes were shaken for 40 s at 6300 rpm. RNA was extracted from the solutions 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.

Reverse transcription (RT) was performed using the Biosystems High Throughput Reverse Transcription Kit (ThermoFisher Scientific, Bridgewater, NJ). Gene expression assay kits 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), polypeptide A II (POLR2A) polymerase (RNA), and master mix sold under the trade name TAQMAN were purchased from ThermoFisher Scientific (Bridgewater, NJ). Quantitative polymerase chain reaction (qPCR) analysis was performed using TaqMan® Master Mix (ThermoFisher Scientific, Bridgewater, NJ) and carried out in 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 compared to untreated or vehicle controls and two-tailed Student's two-sample t-test (Microsoft Office Excel 2007; Microsoft, Redmond, WA, USA).

Method for analyzing RARg transactivation

Retinoic acid receptor gamma (RARg) agonism was assessed using an RARgamma and UAS-BLa-based assay in HEK 293 T cells from GeneBLAzer Invitrogen, in which RARg activation results in beta-lactamase transcription. When fluorescence resonance energy transfer (FRET) sample is added to the cells, FRET is observed. However, following receptor activation and subsequent beta-lactamase expression, the sample is cleaved and FRET is no longer observed.

Cells in culture were washed with phosphate-buffered saline (PBS), trypsinized and resuspended in growth medium, counted using a ViCell cell counter, then an appropriate number of cells were centrifuged and resuspended in assay buffer (0.5E6 cells/mL). 15,000 cells in 30 µL of assay buffer were plated per well in Greiner black-walled, clear flat-bottomed plates using a Combi pipette. The last two columns were filled with assay buffer. 10 µL of 4× concentrated assay samples were added to the cells using a Janus pipette, and the cells were centrifuged at 800 rpm for 2 min without stopping and left at RT for 15 min before incubation at 37 °C overnight.

After 18-20 h of incubation, 8 μl of FRET dye (Invitrogen K1096) were added using a Tempest pipette, the plates were centrifuged at 800 rpm for 2 min continuously and incubated in the dark at room temperature for 2 h. The bottom of the plates was cleaned with an antistatic cleaning wipe before fluorescence was measured using a BMG Pherastar plate reader (using the FRET module, 10 reads, gain for both channels=1000, Ex 409, Em1 460, Em2 530). The average Em1 and Em2 values from wells containing assay buffer only were subtracted from the Em1 and Em2 values, respectively, and the subsequent determination of the Em1/Em2 ratio represents RARg activity. DMSO and ATRA were used as neutral and stimulatory controls, respectively, for normalization.

Extract Acronychia acidula (E1)

Pre-weighed frozen Acronychia acidula fruit was homogenized in a blender for 30 seconds with equal parts denatured alcohol and frozen fruit. The pulp was then mixed and stirred for an additional 24 hours at ambient temperature (22 to 26 degrees Celsius). Additional denatured alcohol was added as needed to ensure good coating of the pulp with alcohol. The mixture was then gravity filtered and the filter cake washed with additional amounts of denatured alcohol. The entire filtrate was then dried under reduced pressure to remove the alcohol. The residue was lyophilized to yield a dry substance free of extracting solvent and water. The extraction was repeated several times on the filter cake with 5-7% extract yields regularly obtained with each extraction. One such batch was prepared using 100 kg of frozen Acronychia acidula fruits and the dried extract (E1) was used in the subsequent experiments described in this paper.

Extract Licaria vernicosa (E2, E3)

Two extractsLicaria vernicosa were obtained at the Baruch S. Bloomberg Institute, Doylestown, Pennsylvania (formerly known as IVHR). The first extract was obtained from the woody portion of the plant (E2), and the second extract was obtained from the roots of the plant (E3). In the IHVR collection nomenclature, the extracts are labeled as IHVR_40256_G10=X-005348-001E002 and as IHVR_40256_E10=X-005346-001M002, respectively. The woody portions and rootsLicaria vernicosa(Mez) Kosterm. was collected in Guyana. 504.3 g of dried ground woody plant material was extracted with methanol sample which was dried under vacuum to yield 10.54 g of crude methanol extract (E2) for X-005348-001E002. 403.8 g of dried ground root material was extracted with methanol sample which was dried under vacuum to yield 18.11 g of crude methanol extract (E3) for X-005346-001M002.

Species extract Actinomyces A5640 (E4)

The general method for culturing and extracting this strain and its extract are registered at the Baruch S. Bloomer Institute, Doylestown, Pennsylvania (formerly known as IVHR). The extract is designated IHVR_39565_F7 in the IHVR collection nomenclature. The extract of Actinomyces species A5640 is referred to herein as E4.

Extracts of Calendula officinalis (E5) and Trigonella foen-graecum (E6)

Extracts of Calendula officinalis (E5) and Trigonella foenum-graecum (E6) were purchased from Caithness Biotechnologies Ltd, UK (http://www.caithnessbiotechnologies.com/). These extracts are part of the Phytotitre Natural Product Library, which is publicly available for purchase. The method for preparing the extracts is described by Caithness Biotechnologies Ltd. as a non-polar method using a mixture of methanol and methylene chloride. Typically, the extraction involves pre-weighing the dried powdered biomass and stirring it in a mixture of methanol/methylene chloride (1:1) overnight at ambient temperature. The suspension is then filtered and the filtrate dried under reduced pressure to give a solvent-free residue. The residue is then dissolved in sufficient 100% DMSO to give a stock solution of 10 mg/mL. This stock solution was used to prepare dilutions in the appropriate screening medium.

Example 1

Gene expression analysis for CRABP2 was performed on formulations containing 0.1% (w/v) Acronychia acidula extract (E1), 0.1% (w/v) Licaria vernicosa extracts (E2 and E3), and 0.1% (w/v) Actinomyces species A5640 extract (E4), each in a 30/70 (v/v) polypropylene glycol/ethanol vehicle. Gene expression was determined according to the gene expression assay described above. The formulations were compared to a 0.1% retinol product sold under the trade name NEUTROGENA RAPID WRINKLE REPAIR (RWR) (Johnson & Johnson Consumer Inc., Skillman, NJ), without treatment and with vehicle treatment. The results are shown in Table 1.

TABLE 1

Without processing Carrier medium RWR (0.1% retinol) 0.1% E1 0.1% E2 0.1% E3 0.1% E4 CRABP2 1.00 0.41 2.43 2.96 1.47 1.88 1.42

Results.

Cellular retinol-binding proteins (CRABPs) are a family of cytoplasmic binding proteins that have been shown to facilitate retinol absorption and prevent spontaneous non-enzymatic isomerization and oxidation of retinol. The CRABP2 (cellular retinoic acid binding protein-II) transcript has been demonstrated to be upregulated by retinol application to human skin both in vivo and in vitro .

This example demonstrates that topical application of the extract compositions of Acronychia acidula , Licaria vernicosa and Actinomyces species A5640 used at a concentration of 0.1% (w/v) to human skin explants induces retinol-like biological activity as demonstrated by the induction of CRABP2 gene expression. Thus, the increase in CRABP2 expression and the associated retinol-like activity indicate skin benefits associated with retinol-like activity, such as improved skin appearance including a reduction in signs of aging including a reduction in fine lines and wrinkles.

Example 2

Gene expression analysis for CRABP2 was performed on formulations containing 0.04% (w/v) to 3% (w/v) Acronychia acidula extract (E1) in a 30/70 (v/v) polypropylene glycol/ethanol vehicle according to the gene expression assay method described above. The formulations were compared to a 0.1% retinol product sold under the trade name NEUTROGENA RAPID WRINKLE REPAIR (RWR) and to vehicle treatment. The results are shown in Table 2.

TABLE 2

Carrier medium 0.04% E1 0.1% E1 1% E1 3% E1 RWR (0.1% retinol) CRABP2 1 ± 0.1 2.35 ± 1.15 4.27 ± 0.44* 7.20 ± 0.81* 5.12 ± 1.50* 6.22 ± 2.84*

Results.

Cellular retinol-binding proteins (CRABPs) are a family of cytoplasmic binding proteins that have been shown to facilitate retinol absorption and prevent spontaneous non-enzymatic isomerization and oxidation of retinol. The CRABP2 (cellular retinoic acid binding protein-II) transcript has been demonstrated to be upregulated by retinol application to human skin both in vivo and in vitro .

This example shows that topical application of Acronychia acidula extract formulations used at concentrations ranging from 0.04% (w/v) to 3% (w/v) to human skin explants induced retinoic acid CRABP2 gene expression in human skin explants upon topical application*, p<0.05. Acronychia acidula extracts elicit retinol-like bioactivity as demonstrated by induction of CRABP2 gene expression similar to the reference 0.1% RWR retinol used in the assay as a positive control.

Example 3

Gene expression analysis for HAS3, UGCG, and HbEGF was performed using a 0.1% (w/v) Acronychia acidula extract (E1) formulation in a 30/70 (v/v) polypropylene glycol/ethanol vehicle according to the gene expression assay method described above. The formulations were compared with a 0.1% retinol product sold under the trade name NEUTROGENA RAPID WRINKLE REPAIR (RWR) with and without vehicle treatment. The results are shown in Table 3.

Increased expression of these genes indicates skin benefits associated with retinol-like activity, such as improved skin appearance, including reduced signs of aging, including reduced fine lines and wrinkles. Increased expression of UCGC genes results in increased formation of glycosylated ceramide, which enhances epidermal lipid production, which strengthens the skin barrier.

TABLE 3

Without processing Carrier medium RWR (0.1% retinol) 0.1% E1 HAS3 1 ± 0.0 1.58 ± 1.32 3.49 ± 1.73* 2.60 ± 1.27* HbEGF 1 ± 0.0 1.35 ± 0.76 7.16 ± 2.69* 6.18 ± 1.95* UGCG 1 ± 0.0 1.99 ± 1.07 4.60 ± 3.33 4.42 ± 2.15*

Results.

The genes heparin-binding epidermal growth factor (HbEGF) and hyaluronic acid synthase 3 (HAS3) are also induced by retinol. HbEGF is known to increase skin thickness, skin density, and prevent skin thinning due to steroid treatment, while HAS3 improves skin hydration. UGCG is an enzyme involved in the synthesis of ceramides in humans and is known to improve the skin barrier.

Example 3 shows that topical application of 0.1% (w/v) Acronychia acidula extract compositions to human skin explants induced HAS3, HbEGF, and ceramide glucosyltransferase (UGCG) gene expression similar to RWR, 0.1% retinol in human skin explants when applied topically*, p< 0.05.

Example 4

Human skin explant biopsies measuring 10 mm were topically applied with either 30/70 (v/v) polypropylene glycol/ethanol vehicle alone or with a 1% (w/v) Acronychia acidula extract (E1) formulation in 30/70 (v/v) polypropylene glycol/ethanol vehicle for seven days and its effect on elastin fiber formation was examined. In addition, 0.1% retinol-containing formulation was also topically applied to human skin explants as a positive control. Moreover, human skin explant samples were left untreated as a negative control. After 7 days, skin biopsies were fixed in 10% buffered formalin (Thermo Fisher Scientific, Hudson, NH), dried, and then embedded in paraffin. Five-micrometer-thick sections were collected from each biopsy. Sections were stained with Luna (American HistoLabs, Gaithersburg, MD) to document elastin fibers as purple. Images of 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% Acronychia acidula extract (E1), and 0.1% retinol.

Results.

In contrast to untreated human skin samples or skin samples treated with a 30/70 (v/v) polypropylene glycol/ethanol vehicle solution by topical application, an increase in elastin fiber formation was observed in the epidermal-dermal region of human skin explants to which a 1% (w/v) Acronychia acidula extract (E1) composition in a 30/70 (v/v) polypropylene glycol/ethanol vehicle solution was topically applied for seven days, similar to what was observed using a composition containing 0.1% retinol as an experimental positive control.

Increased elastin formation results in skin that is more elastic and less prone to the signs and symptoms of skin aging, such as wrinkles. Increased elastin fiber formation is a known retinol-induced anti-aging effect of skin that is associated with improved skin appearance, including a reduction in the signs of aging, including a reduction in fine lines and wrinkles. Thus, the increase in elastin fiber formation by Acronychia acidula extract represents a retinol-like activity and indicates a retinol-like effect on the skin, such as an improvement in skin appearance, including a reduction in the signs of aging, including a reduction in fine lines and wrinkles.

Example 5

The 10 mm human skin explant biopsies were topically applied with either 30/70 (v/v) polypropylene glycol/ethanol vehicle alone or with 1% (w/v) Acronychia acidula extract (E1) composition in 30/70 (v/v) polypropylene glycol/ethanol vehicle for seven days and its effect on elastin fiber formation was examined. In addition, the human skin explants were also topically applied with 0.1% retinol-containing composition as an experimental positive control for comparison. Moreover, the human skin explant samples were left untreated as an experimental negative control for comparison. After 7 days, skin biopsies were fixed in 10% buffered formalin (Thermo Fisher Scientific, Hudson, NH), dried, and then embedded in paraffin. Five-micrometer-thick sections were cut from each biopsy. Sections were stained with Herovici stain (American HistoLabs, Gaithersburg, MD) to document procollagen as blue. Images of skin explants were obtained using a Leitz microscope and a Leica camera (Leica, Allendale, NJ). Figure 2 shows images of skin explants, including untreated, vehicle-treated, 1% Acronychia acidula extract (E1), and 0.1% retinol-treated.

Results.

In contrast to untreated human skin samples or skin samples treated with a 30/70 (v/v) polypropylene glycol/ethanol vehicle solution by topical application, an increase in procollagen formation was observed in the epidermo-dermal region of human skin explants to which a 1% (w/v) Acronychia acidula extract (E1) formulation in a 30/70 (v/v) polypropylene glycol/ethanol vehicle solution was topically applied for seven days, similar to what was observed using a formulation containing 0.1% retinol as an experimental positive control.

Increased procollagen formation results in firmer skin that is more elastic and less prone to the signs and symptoms of skin aging, such as wrinkles, and improves hydration and skin barrier function. Increased procollagen formation is a known retinol-induced anti-aging effect of skin that is associated with improved skin appearance, including reduced signs of aging, including reduced fine lines and wrinkles. Thus, increased procollagen formation by Acronychia acidula extract represents a retinol-like activity and indicates a retinol-like effect on skin, such as improved skin appearance, including reduced signs of aging, including reduced fine lines and wrinkles.

Example 6

Various extracts of Calendula officinalis (E5) and Trigonella foengraecum (E6) were tested using the RARg transactivation assay at 50 μg/ml on two separate days, with replicates on the first of the two days. Extracts providing less than 15% receptor activation were considered inactive. Extracts providing greater than 25% receptor activation were active.

The results are shown in Table 4.

TABLE 4

Extract Part of the plant used Extract type RARg activity E5 Flowers Polar Inactive E5 Petals Polar Inactive E6 Leaves Polar Inactive E6 Seeds Polar Inactive E5 Flowers Non-polar Inactive E5 Petals Non-polar Active E6 Leaves Non-polar Active E6 Seeds Non-polar Inactive

Non-polar extracts of Calendula officinalis petals and, in particular, Trigonella foen-graecum leaves were significant activators of RARg. In contrast, other extracts from each of the two plants were found to be inactive when tested at a concentration of 50 μg/ml.

Subsequent dose-response experiments using the RARg transactivation assay were performed on the two active extracts E5 and E6, as well as on extracts of Acronychia acidula fruit (E1), Licaria vernicosa wood (E2), Licaria vernicosa root (E3), and Actinomyces bacteria (E4), which also confirmed RARg activity using the RARg transactivation assay.

The results are shown in Table 5.

TABLE 5

Extract Source Part of the plant used Extract type EC50 (µg/ml) E5 Calendula Officinalis Petals Non-polar 7.9 E6 Trigonella foengraecum Leaves Non-polar 13.5 E1 Acronychia acidula Fruit Non-polar 1.9 E2 Licaria vernicosa Wood Non-polar 21.9 E3 Licaria vernicosa Root Non-polar 32.2 E4 Species Actinomyces A5640 (Cell culture) Non-polar > 100

The effects of the extracts on cell viability were assessed and no toxicity was observed.

Example 7

The compound 3-(4-farnesyloxyphenyl)-propionic acid was tested using the RARg transactivation assay as follows.

3-(4-Farnesyloxyphenyl)-propionic acid was obtained from Organix Inc., Woburn, MA, USA. A standard synthetic route was followed to yield 100 mg of compound with a purity of >98%. All spectral data confirmed the structural configuration of 3-(4-farnesyloxyphenyl)-propionic acid.

The compound was tested as a solution in DMSO at various concentrations to estimate the EC50 value, which was 0.22 μg/mL.

Example 8

The effect of 3-(4-farnesyloxyphenyl)propionic acid on skin hyperkeratinization was tested as follows.

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

The results are shown in Table 6.

TABLE 6

Tested composition Thickness of the stratum corneum in the layer (% of the total epidermis) % hyperkeratinization (normalized to 10% OK) Average value Standard deviation Average value Standard deviation 10% oleic acid 50% 9% 100% 17% 10% oleic acid + 1 μM 3-(4-farnesyloxyphenyl)-propionic acid 38% 7% 76% 8%

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

Acne vulgaris is a disease of the pilosebaceous complex with a multifactorial pathogenesis, including hyperkeratosis. Excess unsaturated free fatty acids in sebum secretion in acne subjects can contribute to the disruption of the skin barrier associated with an increase in the thickness of the follicular stratum corneum and inflammation observed in acne. It is known that oleic acid can cause hyperkeratosis in human skin epidermal equivalents, mimicking acne histopathology (Li, 2017). Accordingly, the compositions according to the invention containing 3-(4-farnesyloxyphenyl)-propionic acid can be advantageously used for the treatment of acne and other conditions associated with hyperkeratosis.

Claims (13)

1. A method for eliminating signs of skin aging, comprising topical application to skin in need of eliminating signs of skin aging, of a composition containing 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester, wherein said 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester are synthesized or contained in a polar extract of Acronychia acidula fruits, characterized in that a sign of skin aging is a decrease in the synthesis of collagen or elastin, and in that the composition contains from greater than zero to 4% by weight of 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester, based on the total weight of the composition. 2. The method according to claim 1, characterized in that 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester are synthesized. 3. The method according to claim 1 or 2, characterized in that the composition contains from 1% to 4% by weight of 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester, based on the total weight of the composition. 4. The method according to claim 1, characterized in that the composition also contains a cosmetically acceptable carrier. 5. A method for improving the properties of the skin barrier, comprising topical application to the skin in need of improving the function of the skin barrier and moisturizing, of a composition containing 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester, wherein said 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester are synthesized or contained in a polar extract of the fruits of Acronychia acidula , characterized in that the composition contains from greater than zero to 4% by weight of 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester, based on the total weight of the composition. 6. The method according to claim 5, characterized in that 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester are synthesized. 7. The method according to claim 5 or 6, characterized in that the composition contains from 1% to 4% by weight of 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester, based on the total weight of the composition. 8. The method according to claim 5, characterized in that the composition also contains a cosmetically acceptable carrier. 9. The method according to claim 5, characterized in that said local application increases the level of hyaluronic acid in the skin. 10. A method for treating acne, comprising topical application to skin in need of acne treatment of a composition containing 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester, wherein said 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester are synthesized or contained in a polar extract of the fruits of Acronychia acidula , characterized in that the composition contains from greater than zero to 4% by weight of 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester, based on the total weight of the composition. 11. The method according to claim 10, characterized in that 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester are synthesized. 12. The method according to claim 10 or 11, characterized in that the composition contains from 1% to 4% by weight of 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester, based on the total weight of the composition. 13. The method according to claim 10, characterized in that the composition also contains a cosmetically acceptable carrier.