阅读说明：本技术 包含异常毕赤酵母和n-乙酰基葡糖胺的局部用组合物 (Topical composition comprising pichia anomala and N-acetylglucosamine ) 是由 M·兰德哈瓦 M·D·德福特 P·科尼石 P·迈特拉 于 2019-08-29 设计创作，主要内容包括：本发明题为“包含异常毕赤酵母和N-乙酰基葡糖胺的局部用组合物”。本发明提供了一种局部用组合物,所述局部用组合物包含异常毕赤酵母的提取物和n-乙酰基葡糖胺。(The present invention is directed to a topical composition comprising pichia anomala and N-acetylglucosamine. The present invention provides a topical composition comprising an extract of pichia anomala and n-acetylglucosamine.)

1. A topical composition comprises an extract of Pichia anomala and n-acetylglucosamine.

2. The topical composition of claim 1, wherein the pichia anomala extract is prepared from a pichia anomala strain present on fruit or leaves of kiwi fruit.

3. The topical composition of claim 1, wherein the extract of pichia anomala is prepared from a pichia anomala strain present on sugar cane.

4. The topical composition of claim 1, wherein the weight ratio of pichia anomala extract to n-acetylglucosamine in the topical composition is about 0.026.

5. The topical composition of claim 1, further comprising at least 4% by weight of glycerin.

6. The topical composition of claim 1, having a pH of about 6.5 or less.

7. A topical composition comprising about 0.052 wt.% of an extract of pichia anomala and about 2 wt.% n-acetylglucosamine.

8. The topical composition of claim 7, further comprising from about 1 to about 2% by weight of a mixture of olive oil cetyl ester and olive oil sorbitol ester, from about 4 to about 5% by weight of glycerin, and at least about 65% by weight of water, and having a pH of less than about 6.

9. A method of treating signs of skin aging comprising topically applying to skin in need of treatment for skin aging a topical composition comprising an extract of pichia anomala and n-acetylglucosamine.

10. A method of improving skin barrier function and moisture retention comprising topically applying to skin in need of improvement of skin barrier function and moisture retention a composition comprising an extract of pichia anomala and n-acetylglucosamine.

11. A method of increasing the amount of hyaluronic acid produced by skin when contacted with an extract of pichia anomala, comprising contacting the skin with a composition comprising the extract of pichia anomala and n-acetylglucosamine.

12. The method of claim 11, wherein the composition contains about 0.052 wt.% of the extract of pichia anomala and about 2 wt.% n-acetylglucosamine.

13. The method of claim 12, wherein the composition further comprises from about 1 to about 2% by weight of a mixture of olive oil cetyl ester and olive oil sorbitol ester, from about 4 to about 5% by weight of glycerin, and at least about 65% by weight of water, and has a pH of less than about 6.

Technical Field

The present invention provides a method of treating skin by topically applying to the skin a combination of an extract of pichia anomala and n-acetylglucosamine. In addition, the present invention provides a topical composition comprising a combination of an extract of pichia anomala and n-acetylglucosamine.

Background

Hyaluronic acid is present in the skin at the periphery of collagen and elastin fibers and at the intersections of these fibers. Hyaluronic acid is located not only in the dermis, but also in the epidermal intercellular spaces, especially in the middle spinous layer, but not in the Stratum Corneum (SC) or the granular layer. In aging skin, the level of hyaluronic acid is reduced and it separates from collagen and elastin. Skin containing reduced hyaluronic acid levels also exhibits reduced water binding, which may involve the noted changes in aging skin, including wrinkling, altered elasticity, reduced firmness, and reduced ability to support the skin's microvasculature. As one of the primary glycosaminoglycans (GAGs), hyaluronic acid can bind 1000 times its weight of water and can help the skin retain and retain water. It is present in all connective tissues and is produced mainly by fibroblasts and keratinocytes in the skin.

Different methods have been proposed for combating wrinkles and fine lines, including the injection of hyaluronic acid. The injected exogenous hyaluronic acid can be used as a temporary epidermal filler in soft tissue augmentation surgery. However, injected hyaluronic acid has a limited lifetime. On the other hand, it has proven difficult to achieve penetration of the exogenous hyaluronic acid into the skin by topical application.

Pichia pastoris is a genus of Saccharomyces in the family Saccharomyces. Over 100 species are known in this genus. The best known species include Pichia anomala, Pichia guilliermondii, Pichia norwegiae and Pichia anomala.

Pichia anomala (formerly known as Hansenula anomala) can be present in raw milk and cheese. The extract of yeast of the genus pichia is rich in mannan (polysaccharide composed of mannose monomers). Pichia anomala and mannan are known to be useful in the treatment of skin aging. See, e.g., FR 2938768, FR 2906719, FR 2897266 and FR 2976490.

Is a commercially available cosmetic ingredient containing an extract of pichia anomala. It is produced by a pichia strain isolated from sugar cane. It was purchased from Silab-France.

US 2017/0172913a1 relates to topical compositions comprising a combination of pichia anomala extract and chicory root extract providing increased production of hyaluronic acid and methods of treating signs of skin aging and improving skin barrier protection and skin moisturization.

N-acetyl glucosamine is the sugar amine and building block of GAG. It is used in a variety of cosmetic skin care products, such as NeoStrata skin active retinol + NAG compounds commercially available from NeoStrata Company Inc.

U.S. patent No. RE41339 discloses a variety of n-acetyl aldehydic amines, n-acetyl amino acids and other n-acetyl compounds, including n-acetyl glucosamine, that are useful for topical application on the skin, nails, and hair. These compounds provide a variety of anti-aging benefits, such as reduction of thinning skin, fragile skin, fine lines, wrinkles, and the like.

Pichia anomala extract and n-acetylglucosamine act through different biological mechanisms and lead to improvements of different clinical beneficial effects. N-acetylglucosamine is known as one of the substrates required for HA production. Pichia anomala extract acts via a hydration pathway by increasing the activity of the hyaluronan synthase 2 enzyme, thereby translating into clinically beneficial effects including hydration, improved skin barrier, firmness, and the like.

While the art provides separate topical applications of an extract of pichia anomala and n-acetylglucosamine, applicants have now found that topical application of a combination of these two components in relatively low amounts still unexpectedly provides superior activity to produce hyaluronic acid. This can use low cost amounts of active (especially pichia anomala extract) to provide significant benefits to the skin, including improving, reducing, inhibiting or retarding the appearance of at least one sign of skin aging and enhancing skin barrier protection and skin moisturization. Thus, new methods are now available, for example, to treat the signs of skin aging.

Disclosure of Invention

The present invention relates to a topical composition comprising an extract of pichia anomala and n-acetylglucosamine.

The present invention also relates to a topical composition comprising about 0.052 wt.% of an extract of pichia anomala and about 2 wt.% of n-acetylglucosamine.

The present invention also relates to a method of treating signs of skin aging comprising topically applying to skin in need of treatment for skin aging a topical composition comprising an extract of pichia anomala and n-acetylglucosamine.

The present invention also provides a method of improving skin barrier function and moisture retention comprising topically applying a composition comprising an extract of pichia anomala and n-acetylglucosamine to skin in need of improvement in skin barrier function and moisture retention.

The present invention also provides a method of increasing the amount of hyaluronic acid produced by skin when contacted with an extract of pichia anomala, the method comprising contacting the skin with a composition comprising an extract of pichia anomala and n-acetylglucosamine.

Detailed Description

The topical composition of the present invention improves hyaluronic acid production in skin by the synergistic effect of an extract of pichia anomala and n-acetylglucosamine.

It is believed that one skilled in the art can, based on the description herein, utilize the present invention to its fullest extent. The following specific embodiments are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In addition, all publications, patent applications, patents, and other references mentioned herein are incorporated by reference. Percentages used to express amounts of ingredients are weight percentages (i.e.,% (W/W)), unless otherwise indicated. Similarly, the weight ratios used to express the relative proportions of the ingredients are also determined using weight percentages (i.e., the weight ratio is calculated by dividing the weight percentage of one ingredient by the weight percentage of another ingredient). Unless otherwise stated, all ranges are inclusive, e.g., "4 to 9" includes the endpoints 4 and 9.

As used herein, a "product" is optionally in the form of a finished package. In one embodiment, the package is a container, such as a plastic, metal or glass tube or can, containing the composition. The product may also contain additional packaging such as a plastic or cardboard box for storing such containers. In one embodiment, the product comprises a composition of the present invention and contains instructions directing the user to apply the composition to the skin or hair.

As used herein, "topically applying" means directly applying or spreading on the outer skin, scalp or hair, for example, by hand or an applicator such as a wipe, roller, or spray.

As used herein, "cosmetic" refers to a beautification substance or article that retains, restores, imparts, stimulates, or enhances the appearance of a body beauty or appears to enhance the appearance or youthful appearance, especially when referring to the appearance of tissue or skin.

As used herein, "cosmetically acceptable" means that the ingredients described by the term are suitable for use in contact with tissue (e.g., skin or hair) without undue toxicity, incompatibility, instability, irritation, allergic response, and the like.

In certain embodiments, the compositions of the present invention are suitable for treating signs of skin aging. As used herein, "signs of skin aging" include the presence of fine lines and wrinkles, loss of elasticity, uneven skin tone, and scarring. In particularly preferred embodiments, the signs of aging are the presence of fine lines and wrinkles and/or loss of elasticity.

As used herein, "treating signs of skin aging" refers to mitigating, alleviating, preventing, ameliorating, or eliminating the presence or signs of skin aging described above.

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

As used herein, "loss of elasticity" includes a loss of elasticity or structural integrity of skin or tissue, including but not limited to sagging, laxity, and loose tissue. Loss of elasticity or structural integrity of a tissue can be caused by a variety of factors including, but not limited to, disease, aging, hormonal changes, mechanical trauma, environmental damage, or as a result of the application of a product such as cosmetics or pharmaceuticals to the tissue.

As used herein, "uneven skin tone" means a skin condition associated with diffuse or mottled pigmentation, which can be classified as hyperpigmentation, such as post-inflammatory hyperpigmentation.

As used herein, "scarring" means a skin condition associated with redness or erythema.

As used herein, "improving the firmness of skin" means increasing the firmness or elasticity of skin, preventing the loss of firmness or elasticity of skin, or preventing or treating sagging, loose and loose skin. The firmness or elasticity of the skin can be measured by using a skin elasticity tester (curometer). See chapter 66.1 of Handbook of non-Invasive Methods And The Skin, edited by j.cerup, g.jemec And g.grove, 2006. Loss of skin elasticity or firmness may be caused by a variety of factors, including but not limited to aging, environmental damage, or the result of applying cosmetics to the skin.

As used herein, "improving the texture of the skin" means smoothing the skin surface to remove bumps or crevices on the skin surface.

As used herein, "improving the appearance of wrinkles in skin" means the process of preventing, retarding, stopping or reversing the formation of wrinkles and fine lines on skin.

As used herein, the term "safe and effective amount" means an amount sufficient to elicit the desired effect but low enough to avoid serious side effects. The safe and effective amount of the compound, extract or composition will vary with such factors as the age, health and environmental exposure of the end user, the duration and nature of the treatment, the particular extract, ingredient or composition employed, and the particular carrier employed.

As used herein, "skin in need of improved skin barrier function and moisture retention" means, but is not limited to, skin lacking moisture, lacking sebum, cracking, dryness, itching, scaling, dry skin, dehydration, lacking flexibility, lacking luster, lacking gloss, or lacking lipids.

As described herein, applicants have discovered that topical administration of a combination of low levels of an extract of pichia anomala and n-acetylglucosamine can provide unexpectedly good skin barrier function, skin moisturization, and skin anti-aging benefits.

Applicants have also found that topical administration of a composition containing a combination of an extract of pichia anomala and n-acetylglucosamine results in endogenous hyaluronic acid ("HA") levels in the skin that are higher than those achieved using only even higher amounts of an extract of pichia anomala. Topical application of such compositions can increase hyaluronic acid levels to the direction found in younger skin, thereby providing structural support to the skin to reduce the appearance of signs of skin aging.

Pichia anomala

The topical composition comprises one or more extracts of pichia anomala. In particular, such an extract may be an extract produced using one of a variety of pichia anomala strains isolated from fruit or other aerial parts of a plant. Any cosmetically acceptable extract of pichia anomala can be used.

An example of a suitable extract of Pichia anomala is PRO-LIPIISKIN, commercially available from Silab-France. It is produced by a strain of Pichia anomala present on sugarcane.

Another example of a suitable extract of pichia anomala is produced by a pichia anomala strain present on the fruit or leaves of a kiwi plant.

Pichia anomala can be provided as a solution that more contains dry matter (extract) in the range of about 20 wt.%, more specifically 2 to 10 wt.%, and most specifically 3 to 7 wt.%.

Solvents for such solutions include water, alcohols, glycols, and the like. In one embodiment, the solvent is at least about 90% by weight water, or at least about 95% by weight water.

N-acetyl glucosamine

The topical composition further comprises n-acetylglucosamine. N-acetylglucosamine has the following structure:

measurement of

Any suitable amount of pichia anomala extract and n-acetylglucosamine can be used in the compositions of the present invention. Preferably, the composition comprises a safe and effective amount of both ingredients. In particular, the amounts of pichia anomala extract and n-acetylglucosamine used are cosmetically acceptable and are selected to achieve the desired skin treatment for a particular condition (such as signs of aging, reduced barrier function, or reduced moisturization).

In certain preferred embodiments, the composition comprises from about 0.01 to about 1% by weight of pichia anomala extract, more preferably from about 0.025 to about 0.25% by weight of pichia anomala extract. In one embodiment, the composition comprises about 0.052 wt.% of pichia anomala extract.

In certain preferred embodiments, the compositions comprise from about 0.01 to about 10 wt.%, more preferably from about 0.5 to about 5 wt.% n-acetylglucosamine. In one embodiment, the composition comprises about 2% by weight n-acetylglucosamine.

In certain embodiments, the weight ratio of pichia anomala extract to n-acetylglucosamine in the composition is from about 0.01 to about 0.05. In one embodiment, the weight ratio of pichia anomala extract to n-acetylglucosamine in the composition is about 0.026.

Topical compositions

The compositions of the present invention may be topically applied to human skin or hair. Thus, the composition may further comprise a cosmetically acceptable topical carrier, which may be from about 50% to about 99.99% by weight of the composition (e.g., from about 80% to about 99% by weight of the composition). In a preferred embodiment of the present invention, the cosmetically acceptable topical carrier comprises water.

The compositions can be formulated into a variety of product types including, but not limited to, lotions, creams, gels, sticks, sprays, ointments, cleansing liquid lotions and solid soaps, shampoos and conditioners, hair sprays, pastes, foams, powders, mousses, shaving creams, wipes, patches, hydrogels, film-forming products, masks and skin masks, films, and cosmetics such as foundations and mascaras. These product types may contain several types of cosmetically acceptable topical carriers including, but not limited to, solutions, suspensions, emulsions (e.g., microemulsions and nanoemulsions), gels, solids, and liposomes. The following are non-limiting examples of such vectors. Other carriers can be formulated by one of ordinary skill in the art.

The compositions useful in the present invention may be formulated as solutions. The solution typically comprises an aqueous or organic solvent (e.g., from about 50% to about 99.99% or from about 90% to about 99% of a cosmetically acceptable aqueous or organic solvent). Examples of suitable organic solvents include: propylene glycol, polyethylene glycol, polypropylene glycol, glycerin, 1,2, 4-butanetriol, sorbitol esters, 1,2, 6-hexanetriol, ethanol, and mixtures thereof.

The compositions useful in the subject invention may be formulated as a solution comprising an emollient. Such compositions preferably contain from about 2% to about 50% of one or more emollients. As used herein, "emollient" refers to a substance used to prevent or alleviate dryness, such as by preventing transepidermal loss from the skin. Examples of emollients are known in the art. Examples of particularly suitable emollients include vegetable oils, mineral oils, fatty acid esters, and the like.

Lotions can be prepared from such solutions. Lotions typically contain from about 1% to about 20% (e.g., from about 5% to about 10%) of one or more emollients and from about 50% to about 90% (e.g., from about 60% to about 80%) water.

Another type of product that can be formulated from a solution is a cream. Creams typically contain from about 5% to about 50% (e.g., from about 10% to about 20%) of one or more emollients and from about 45% to about 85% (e.g., from about 50% to about 75%) water.

The compositions of the present invention may comprise water, or alternatively be anhydrous or a paste which does not comprise water but comprises an organic solvent and/or a silicone solvent, an oil, a lipid and a wax. The ointment may contain simple animal or vegetable oils or semi-solid hydrocarbon bases. The cream may contain from about 2% to about 10% of one or more emollients and from about 0.1% to about 2% of one or more thickeners.

The composition may be formulated as an emulsion. If the topical carrier is an emulsion, from about 1% to about 10% (e.g., from about 2% to about 5%) of the topical carrier contains one or more emulsifiers. The emulsifier may be nonionic, anionic or cationic. Examples of emulsifiers are well known in the art.

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

Single emulsion skin care formulations of oil-in-water and water-in-oil, such as lotions and creams, are well known in the cosmetic arts and may be used in the subject invention. Multiple emulsion compositions, such as water-in-oil-in-water or oil-in-water-in-oil, can also be used in the subject invention. Generally, such single or multiple emulsion contains water, an emollient, and an emulsifier as major ingredients.

The compositions of the present invention may also be formulated as a gel (e.g., an aqueous gel, an alcoholic/hydrogel, or an oleogel, using a suitable gelling agent or agents). Suitable gelling agents for aqueous and/or alcogels include, but are not limited to, natural gums, acrylic acid and acrylate polymers and copolymers, and cellulose derivatives (e.g., hydroxymethyl cellulose and hydroxypropyl cellulose). Gelling agents suitable 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 about 0.1 to 5% by weight of such gelling agents.

In one embodiment, the composition is a gel cream. The aesthetics of gel creams are characterized by water-blocking, translucent aspects, and light afterfeel. As used herein, the term "gel cream" means a formulation having a low content of oil droplets suspended in an aqueous gel matrix.

The compositions of the present invention may also be formulated as solid formulations (e.g., wax-based sticks, bar compositions, powders, or wipes containing powders).

In addition to the above components, the composition may contain a variety of other oil-soluble and/or water-soluble materials commonly used in compositions for application to the skin and hair at levels established in the art.

Additional cosmetic active agents

The compositions of the present invention may also comprise any of a variety of additional cosmetically active agents. Examples of suitable additional active agents include: skin lightening agents, tanning agents, additional anti-aging agents, tropoelastin promoters, collagen promoters, anti-acne agents, oil control agents, antimicrobial agents (such as anti-yeast, anti-fungal and anti-bacterial agents), anti-inflammatory agents, anti-parasitic agents, external analgesics, sunscreens, photoprotective agents, antioxidants, keratolytic agents, detergents/surfactants, moisturizers, nutrients, vitamins, energy enhancers, antiperspirants, astringents, deodorants, depilatories, hair growth enhancers, hair growth retardants, firming agents, moisturizers, synergists, anti-sclerosants, skin conditioners, anti-cellulite agents, odor control agents such as odor masking agents or pH adjusters and the like.

Examples of various suitable additional cosmetically acceptable actives include hydroxy acids; benzoyl peroxide; d-panthenol; UV filtration such as, but not limited to, avobenzone (Parsol 1789), disodium phenylbisbenzimidazole tetrasulfonate (Neo Heliopan AP), diethylamino hydroxybenzoylbenzoic acid hexyl ester (Uvinul A Plus), encampane (Mexoryl SX), methyl anthranilate, 4-aminobenzoic acid (PABA), cinoxate, ethylhexyl triazone (Uvinul T150), homosalate, 4-methylbenzylidenecamphor (Parsol 5000), octyl methoxycinnamate (Octinoxate), octyl salicylate (Octisalate), octyl dicarbamate (Escalol 507), phenylbenzimidazole sulfonic acid (Ensulizole), polysiloxane-15 (Parsol SLX), triethanolamine salicylate, bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorbs), benzophenone 1-12, dihydroxybenzone, cresol, trazol trioxane (Mexoryl XL), diethylhexylbutamido HERB (Uvasorb) B, Octocrylene, oxybenzone (Eusolex4360), sulibenzone, methylene bis-benzotriazolyl tetramethylbutylphenol (Tinosorb M), titanium dioxide, zinc oxide; a carotenoid; a free radical scavenger; a spin-trapping agent; retinoids and retinoid precursors, such as retinol/retinoic acid and retinyl palmitate; a ceramide; a polyunsaturated fatty acid; essential fatty acids; an enzyme; an enzyme inhibitor; a mineral; hormones, such as estrogens; steroids, such as hydrocortisone; 2-dimethylaminoethanol; copper salts such as copper chloride; copper-containing peptides, coenzyme Q10; amino acids such as proline; a vitamin; lactobionic acid; acetyl-coenzyme A; nicotinic acid; riboflavin; thiamin; ribose; electron transporters such as NADH and FADH 2; and other plant extracts such as oat, aloe, agrimony, soy, shiitake extracts, and derivatives and mixtures thereof.

In certain preferred embodiments, the composition comprises a combination of pichia anomala extract and n-acetylglucosamine and at least one additional skin moisturizing active.

Examples of suitable additional agents that improve the appearance of at least one sign of skin aging include, but are not limited to, tropoelastin promoters, collagen promoters, retinoids, hyaluronic acid (including cross-linked hyaluronic acid), dimethylaminoethanol, N' -tetrakis (2-hydroxypropyl) ethylenediamine, α hydroxy acids, polyhydroxy acids, and combinations of two or more thereof.

As used herein, "tropoelastin promoter" refers to a class of compounds that have the biological activity of enhancing tropoelastin production. According to the present invention, tropoelastin promoters include all natural or synthetic compounds capable of enhancing the production of tropoelastin in the human body.

Examples of suitable tropoelastin promoters include, but are not limited to, blackberry extracts, cotinus coggygria extracts, feverfew extracts, and bimetallic complexes having a copper and/or zinc component. The bimetallic complex having a copper and/or zinc component can be, for example, copper-zinc citrate, copper-zinc oxalate, copper-zinc tartrate, copper-zinc malate, copper-zinc succinate, copper-zinc malonate, copper-zinc maleate, copper-zinc aspartate, copper-zinc glutamate, copper-zinc glutarate, copper-zinc fumarate, copper-zinc glucarate, copper-zinc polyacrylate, copper-zinc adipate, copper-zinc pimelate, copper-zinc suberate, copper-zinc azelate, copper-zinc sebacate, copper-zinc dodecanoate, or a combination thereof. In a preferred embodiment, the tropoelastin promoter is selected from the group consisting of blackberry extracts, cotinus coggygria extracts, feverfew extracts, and combinations thereof. In a particularly preferred embodiment, the tropoelastin promoter is selected from the group consisting of blackberry extracts, feverfew extracts, and combinations thereof.

By "blackberry extract" is meant a blend of compounds isolated from a plant of the genus Rubus (Rubus) and preferably Rubus vietnamensis (Rubus fructicosus). In one embodiment, the compound is isolated from a flower of the plant. In another embodiment, the compound is isolated from dried flowers of the plant. Such compounds can be isolated from one or more parts of a plant (e.g., the entire plant, flowers, seeds, roots, rhizomes, stems, fruits, and/or leaves of the plant). In a preferred embodiment, the blackberry extract is a blackberry leaf extract. One particularly suitable blackberry extract is prepared by extracting the vietnamese raspberry leaf with a mixture of water and ethanol, with a maltodextrin base (commercially available from Symrise Inc., terboro, NJ) and sold under the name SymMatrix) having a compounding activity of about 5% to about 10%.

The compositions of the present invention may comprise a cosmetically effective amount of one or more tropoelastin promoters, such as those described above. Preferably, the composition comprises from about 0.1% to about 10% of the tropoelastin promoter, more preferably from about 0.5% to about 5% of the tropoelastin promoter, and most preferably from about 0.5% to about 2% of the elastin promoter, on an active basis.

As used herein, "collagen promoter" refers to a compound having biological activity that enhances collagen production. According to the present invention, "non-retinoid collagen promoters" include all natural or synthetic compounds which are not retinoids or are derived from retinoids and are capable of enhancing collagen production in the human body.

Examples of suitable collagen promoters include, but are not limited to, the following: retinoids (including retinol, retinal and retinoic acid), feverfew (Tanacetum parthenium) extract, Centella asiatica (Centella asiatica) extract and Siegesbeckia orientalis (Siegesbeckia orientalis) extract; an extract of soybean; a collagen promoting peptide; ursolic acid; and asiaticoside.

Centella asiatica, also known as violet bamboo basket (Violette marron) on niwana, known as Kola (Gotu Kola) or suavena indica (Indian pennywort) in india, known as centella asiatica R in north america (centella asiatica), and known as tarapetraka in maxgaca, is a polymorphous herb belonging to the family of the Umbelliferae (Apiaceae), in particular to the subfamily coriander (Hydrocotyle). It grows wildly throughout the tropical zone and prefers humid shaded areas with elevations of about 600 to 1200 meters. Centella asiatica has three varieties: the dibuca type, the arbixinib subtype and the florida type. The herb is known and used for its healing, sedative, analgesic, antidepressant, antiviral and antimicrobial properties. The biological activity of the herb appears to be due to the presence of triterpene molecules in the herb. Suitable centella asiatica extracts are available as TECA from Bayer Consumer HealthCare (Basel, Switzerland).

By "siegesbeckia orientalis extract" is meant any of the various extracts of the plant siegesbeckia orientalis, including siegesbeckia glycosides available from Sederma International Group, Edison, NJ.

Suitable collagen promoting peptides include matrine peptides (i.e., peptides derived from degradation of extracellular matrix proteins-collagen, elastin, or proteoglycans), including palmitoyl pentapeptides, such as MATRIXYL from Sederma (Croda international group of Edison, NJ); GHK copper peptide from Photodex of Montgomeryville (PA) as PROCYTE; palmitoyl GHK peptide purchased from Sederma (Croda International Group of Edison, NJ) as biopotede CL; biomimetic tetrapeptides such as those available as Chronoline Tri Peptide from Unipex, quebec, Canada; and the palmitoyl tripeptide from DSM, Basel, Switzerland, available as Syn-Coll.

Ursolic acid is also known as pentacyclic triterpenic acid, ursolic acid, Urson, β -ursolic acid, and 3- β -hydroxy-ursol-12-ene-28-carboxylic acid, which is commercially available, for example, from Sigma-Aldrich, st.

Asiaticoside, also chemically known as: [6- [ [3, 4-dihydroxy-6- (hydroxymethyl) -5- (3,4, 5-trihydroxy-6-methyltetrahydropyran-2-yl) oxytetrahydropyran-2-yl ] oxymethyl ] -3,4, 5-trihydroxy tetrahydropyran-2-yl ]10, 11-dihydroxy-9- (hydroxymethyl) -1,2,6a,6b,9,12 a-hexamethyl-2, 3,4,5,6,6a,7,8,8a,10,11,12,13,14 b-decatetrahydro-1H-picene-4 a-carboxylate ], commercially available, for example, from Bayer Sant Familiole Division Serdex,69, Boulevar Victor Hugo 93400SAINT-OUEN France.

The compositions of the present invention may comprise a cosmetically effective amount of one or more collagen promoters. Preferably, the composition comprises from about 0.1% to about 10% collagen promoter, more preferably from about 0.5% to about 5% collagen promoter, and most preferably from about 0.5% to about 2% collagen promoter, on an active basis.

The compositions of the present invention may additionally comprise at least one skin lightening active. Examples of suitable skin lightening actives include, but are not limited to, tyrosinase inhibitors, melanin degrading agents, melanosome transfer inhibitors including PAR-2 antagonists, exfoliating agents, sunscreens, retinoids, antioxidants, tranexamic acid, cetyl tranexamate hydrochloride, skin bleaching agents, linoleic acid, adenosine monophosphate disodium salt, chamomile extract, allantoin, sunscreens, talc and silica, zinc salts, and the like, as well as other agents as described in Solano et al, Pigment Cell Res.19 (550-.

Examples of suitable tyrosinase inhibitors include, but are not limited to, vitamin C and derivatives thereof, vitamin E and derivatives thereof, kojic acid, arbutin, resorcinol, hydroquinone, flavones such as licoflavonoids, licorice root extract, mulberry root extract, dioscorea composita root extract, saxifrage extract, and the like, ellagic acid, salicylates and derivatives, glucosamine and derivatives, fullerenes, hinokitiol, diacids, 5 '-dipropyl-biphenyl-2, 2' -diol (magnolol), 4- (4-hydroxyphenyl) -2-butanol (4-HPB), and combinations of two or more thereof, examples of vitamin C derivatives include, but are not limited to, ascorbic acid and salts, ascorbic acid-2-glucoside, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, and C-rich natural extracts, examples of vitamin E derivatives include, but are not limited to, α -tocopherol, β -tocopherol, gamma-tocopherol, delta-tocopherol, α -tocotrienol, β -tocotrienol, syn-tocopherol, gamma-tocopherol, 4-tocopherol, esters, and esters including, as exemplified by salicylic acid, derivatives, salicylic acid, derivatives, and derivatives, salicylic acid derivatives, salicylic acid derivatives, salicylic acid derivatives, salicylic acid, salicylic.

Examples of suitable melanin degrading agents include, but are not limited to, peroxides and enzymes, such as peroxidases and ligninases. In certain preferred embodiments, the melanin-inhibiting agent comprises a peroxide or ligninase.

Examples of suitable melanosome transfer inhibitors 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 certain preferred embodiments, the melanosome transfer inhibitor comprises soy extract or niacinamide.

Examples of exfoliating agents include, but are not limited to, α -hydroxy acids such as lactic acid, glycolic acid, malic acid, tartaric acid, citric acid, or any combination of any of the foregoing, β -hydroxy acids such as salicylic acid, polyhydroxy acids such as lactobionic acid and gluconic acid, and mechanical exfoliation such as microdermabrasion.

Examples of retinoids include, but are not limited to, retinol (vitamin a alcohol), retinal (vitamin a aldehyde), retinol acetate, retinol propionate, retinol linoleate, retinoic acid, retinol palmitate, isotretinoin, tazarotene, bexarotene, adapalene, combinations of two or more thereof, and the like. In certain preferred embodiments, the retinoid is selected from: retinol, retinal, retinol acetate, retinol propionate, retinol linoleate, and combinations of two or more thereof. In certain more preferred 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-acetyl cysteine, glutathione), lipoic acid and dihydrolipoic acid, stilbene compounds such as resveratrol and derivatives, lactoferrin, iron and copper chelators, and ascorbic acid derivatives (e.g., ascorbic acid-2-glucoside, ascorbyl palmitate, and ascorbyl polypeptide). Oil-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 retinol palmitate), tocopherols (e.g., tocopheryl acetate), tocotrienols, and ubiquinones. Natural extracts containing antioxidants suitable for use in the compositions of the present invention include, but are not limited to: extracts containing flavonoids and isoflavones and their derivatives (e.g., genistein and lignoisonoflavone (diadzein)), extracts containing resveratrol, and the like. Examples of such natural extracts include grape seed, green tea, black tea, white tea, pine bark, feverfew without parthenolide, oat extract, blackberry extract, cotinus coggygria extract, soybean extract, grapefruit extract, malt extract, hesperetin, grape extract, purslane extract, licochalcone, chalcone, 2' -dihydroxychalcone, primula extract, propolis, and the like.

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

The compositions of the present invention may comprise a cosmetically effective amount of one or more anti-inflammatory compounds.

Examples of suitable anti-inflammatory agents include substituted resorcinols, (E) -3- (4-methylphenylsulfonyl) -2-acrylonitriles (e.g., "Bay 11-7082" commercially available from sigma aldrich of san louse, missouri), tetrahydrocurcumines (e.g., tetrahydrocurcumin CG, available from sabina corporation of Piscataway, NJ), extracts and materials from: cortex Phellodendri (phellodendron amurense) outer skin extract (PCE), undenatured soybean (Glycine max)), feverfew (chamomile (tanacettura), ginger (ginger) officinalis)), Ginkgo biloba (Ginkgo biloba)), madecassoside (centella asiatica extract component), cotinus coggygria (cotinus coggygria), Petasites japonicus extract (Petasites hybridus), Lycium barbarum (Lycium barbarum), milk thistle extract (Silybum marianum), honeysuckle (honeysuckle japonica), Peru balsam (myrtle), myrtle (myrtle) peri), sage (Salvia officinalis)), cranberry extract (mangosteen cranberry (valerian), and black vine extract (black raspberry), Amaranthus officinalis (Amaranthus mangostachys), and lily (Amaranthus mangachene (Liliaceae)), and black currant (Lilium nigrum officinalis (Lilium nigrum officinalis (Lilium officinalis)) and lily (Lilium nigrum officinalis (Lilium officinalis)) extract (Lilium nigrum officinalis (Lilium) and lily extract (Lilium nigrum) are obtained by extracting and extracting the plant (Lilium nigrum officinalis) and extracting the plant (Lilium nigrum officinalis) and the plant, and the plant of the plant, Olive leaf extract (olive (Olea europaea)), phloretin (apple extract), oat flour (oat sativa), Lifenol (hop (Humulus lupulus) extract), formononetin P (formononensis (ononispinos)), licochalcone (licorice: Glycyrrhiza inflata (Glycyrrhiza inflata) extract component), camomile (bisabolol and ginger extract), combinations of two or more thereof, and the like.

In one embodiment, the anti-inflammatory agent is resorcinol. Particularly suitable substituted resorcinols include 4-hexylresorcinol and 4-octylresorcinol, especially 4-hexylresorcinol. 4-hexylresorcinol is commercially available as SYNOVEA HR from Sytheon corporation (Lincoln Park, NJ). 4-Octylresorcinol is commercially available from City Chemical LLC (WestHaven, Connecticut).

By "extract of FEVERFEW" is meant an extract of the plant "TANACETUM PARTHENIUM", such as may be prepared according to the details set forth in U.S. patent application publication 2007/01965233 entitled "PARTHENOLIDE FREE biological extracts in culture FROM fertilizer (TANACETUM PARTHENIUM) AND processing FOR the plant material PRODUCTION". A particularly suitable feverfew extract is commercially available as about 20% active feverfew from Integrated cosmetic Technologies, Inc. (Ossinging, NY).

In the skin care compositions of the present invention, the ratio of the combined pichia anomala extract and n-acetylglucosamine to the amount of the anti-inflammatory compound can vary. For example, the extract and the anti-inflammatory compound may be present in a weight ratio of about 0.001 to about 100, preferably about 0.01 to about 10, more preferably about 0.25 to about 2 (which is determined by dividing the amount by weight of the dry extract by the amount by weight of the anti-inflammatory compound).

Many other materials may also be present in the compositions of the present invention. In certain preferred embodiments, the composition comprises one or more topical ingredients selected from the group consisting of: surfactants, chelating agents, emollients, humectants, conditioning agents, preservatives, opacifiers, fragrances and the like.

Emollients are intended to mean compounds that help maintain the soft, smooth, and pliable appearance of the skin (e.g., by remaining on the skin surface or in the stratum corneum to act as a lubricant). Examples of suitable emollients include those found in chapter 35, page 399-415 (Skin fel Agent by G zochi) in the Handbook of cosmetics science and Technology (edited by a. barel, m.paye and h.maibach, published 2001 by Marcel Dekker, Inc (New York, NY), and include, but are not limited to, petrolatum, hexyldecanol stearate, and vegetable, nut and vegetable oils, such as macadamia nut oil, rice bran oil, grape seed oil, palm oil, evening primrose oil, hydrogenated peanut oil, and avocado oil.

Humectants mean compounds intended to increase the water content of the top layer of the Skin (e.g., hygroscopic compounds.) examples of suitable humectants include those found in chapter 35, chapter 399, page 415 (Skin fel Agent of G zochi) in the Handbook of Cosmetic Science and Technology (edited by a. heel, m.paye, and h.maibach, published 2001, New York, Inc (New York, NY), and include, but are not limited to, glycerol, sorbitol, or trehalose (e.g., α -trehalose, β -trehalose, α -trehalose) or salts or esters thereof (e.g., trehalose 6-phosphate).

In one embodiment, the composition contains glycerin. For example, the composition contains at least about 4% by weight glycerin. The composition may contain at least about 10% by weight of glycerin.

In another embodiment, the composition has a pH of about 6.5 or less. For example, the composition can have a pH of about 5.5 to about 6.

In one embodiment, the composition contains about 0.052 wt.% of an extract of Pichia anomala and about 2 wt.% n-acetylglucosamine.

The composition may also contain from about 1 to about 2% by weight of a mixture of olive oil cetyl ester and olive oil sorbitol ester, from about 4 to about 5% by weight of glycerin and at least about 65% by weight of water, and have a pH of less than about 6.

By surfactant is meant a surfactant intended to be washed or emulsified. Examples of suitable surfactants include those found in Handbook of Cosmetic Science and Technology (edited by a. barel, m.paye and h.maibach, published in 2001 by Marcel Dekker, Inc (New York, NY)), chapter 37, page 431-450 (Classification of surfactants by l.oldenlive de guertechi), and include, but are not limited to, anionic surfactants such as sulfates, cationic surfactants such as betaines, amphoteric surfactants such as sodium cocoyl glycinate, nonionic surfactants such as alkyl polyglucosides.

Examples of suitable chelating agents include those capable of protecting and retaining the compositions of the present invention. Preferably, the chelating agent is ethylenediaminetetraacetic acid ("EDTA"), and more preferably tetrasodium ethylenediaminetetraacetate, which is commercially available from Dow Chemical company (Midland, Michigan) under the tradename VERSENE100 XL.

Suitable preservatives include, for example, parabens, quaternary ammonium species, phenoxyethanol, benzoate salts, DMDM hydantoin, organic acids, and are present in the composition in an amount of from about 0% to about 1%, or from about 0.05% to about 0.5%, based on the total weight of the composition.

Any of a variety of conditioning agents that impart additional attributes to hair, such as shine, are suitable for use in the present invention. Examples include, but are not limited to, volatile silicone conditioning agents having a boiling point below about 220 ℃ at atmospheric pressure. Examples of suitable volatile silicones include, but are not limited to, polydimethylsiloxane, hexamethyldisiloxane, cyclomethicone fluids, polydimethylcyclosiloxanes such as those commercially available under the trade designation "DC-345" from Dow Corning Corporation (Midland, Michigan), and mixtures thereof, and preferably include cyclomethicone fluids. Other suitable conditioning agents include cationic polymers including polyquaterniums, cationic guar gums, and the like.

Any of a variety of commercially available pearlescent or opacifying agents are suitable for use in the compositions. Examples of suitable pearlescent or opacifying agents include, but are not limited to, (a) fatty acids having from about 16 to about 22 carbon atoms and (b) mono-or diesters of ethylene or propylene glycol; (a) a fatty acid having from about 16 to about 22 carbon atoms and (b) formula HO- (JO)_a-a monoester or diester of a polyalkylene glycol of H, wherein J is an alkylene group having from about 2 to about 3 carbon atoms; and a is a monoester or diester of 2 or 3); a fatty alcohol containing from about 16 to about 22 carbon atoms; formula KCOOCH₂A fatty acid ester of L, wherein K and L independently contain from about 15 to about 21 carbon atoms; inorganic solids that are insoluble in the shampoo composition, and mixtures thereof.

Any fragrance composition suitable for use on the skin can be used according to the present invention.

In certain preferred embodiments, the invention is in the form of a substrate comprising the composition of the invention. Any suitable substrate may be used. Examples of suitable substrates and substrate materials are disclosed, for example, in U.S. published patent application nos. 2005/0226834 and 2009/0241242, which are incorporated herein by reference in their entirety.

In certain preferred embodiments, the substrate is a wipe, glove, or mask. Preferably, such embodiments comprise a water insoluble substrate, such substrates being as defined in the documents cited above. For certain embodiments, the water-insoluble substrate may be sized and shaped such that it covers the face of an individual user, thereby facilitating placement of the water-insoluble substrate as a mask substrate around the face of the user. For example, the water-insoluble mask substrate can have openings for the mouth, nose, and/or eye configurations of a user. Alternatively, the water insoluble substrate may be free of such openings. Such an open-free configuration may be used in embodiments of the present invention where the water-insoluble substrate is intended to cover a large non-facial area of the skin or if 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 an arcuate shape such as a circle or an ellipse. For certain embodiments, the substrate is a glove, such as the glove described in U.S. published patent application No. 2006/0141014, which is incorporated herein by reference in its entirety. In one embodiment of the invention, the product comprises a plurality of water insoluble substrates having different shapes.

The present invention also includes a method of improving the barrier function and moisture retention of skin by administering an extract of pichia anomala and n-acetylglucosamine to skin in need of improvement of the barrier function and moisture retention of the skin. The method comprises, for example, topically applying a composition of the present invention comprising a combined pichia anomala extract and n-acetylglucosamine to skin in need of improvement in skin barrier function and moisture retention. Such topical application may be applied to any skin on the body that requires treatment, for example, the skin of the face, lips, neck, chest, back, arms, armpits, hands, feet, and/or legs. The combined pichia anomala extract and n-acetylglucosamine are preferably administered in amounts effective to result in the desired improvement in skin barrier function.

The present invention also includes methods of improving the appearance of at least one sign of skin aging by applying to skin in need of improving the appearance of at least one sign of skin aging a combination of pichia anomala extract and n-acetylglucosamine. The method comprises, for example, topically applying to skin in need of treatment of at least one sign of skin aging a composition of the present invention comprising a combined pichia anomala extract and n-acetylglucosamine. Such topical application may be to any skin on the body in need of treatment, for example, the skin of the face, lips, neck, chest, back, arms, armpits, hands, feet, and/or legs. The combined pichia anomala extract and n-acetylglucosamine are preferably administered in amounts effective to result in an appearance improvement that achieves the desired at least one sign of skin aging.

Any suitable method of applying the composition to skin in need thereof may be used. For example, the composition may be applied to the skin in need by applying it directly to the skin in need by hand from a package, or may be transferred from a substrate such as a wipe or mask, or a combination of two or more thereof. In other embodiments, the compositions may be applied via dropper, tube, roller, sprayer, and patch, or added to a bathtub or otherwise added to water for application to the skin, and the like. The composition may be applied in a variety of ways/forms, including but not limited to as a leave-on cream, mask, and/or serum.

In certain embodiments, the methods of the present invention comprise applying to the skin at least two different compositions or products comprising pichia anomala extract and n-acetylglucosamine. For example, the method can include administering to skin in need of treatment a first composition comprising an extract of pichia anomala, followed by administration of a second composition different from the first composition comprising n-acetylglucosamine.

In certain preferred embodiments, the first and second compositions may be independently selected from lotions, cleansers, masks, wipes, creams, essences, gels, and the like. In certain preferred embodiments, at least one of the first and second compositions is a cleanser, lotion, cream, serum, or serum, and the other is a mask or wipe. In certain other preferred embodiments, at least one of the first and second compositions is a cleanser and the other is a lotion or cream.

Compositions and formulations and products containing such compositions of the invention can be prepared using methods well known to those of ordinary skill in the art. These compositions are useful for treating aged skin, such as wrinkles, loss of elasticity, uneven skin tone, including reducing scarring. The compositions may be based on conventional use and are substantially free of skin irritation.

In one embodiment, the present invention provides a method of increasing the amount of hyaluronic acid produced by skin when contacted with an extract of pichia anomala, the method comprising contacting the skin with a composition comprising an extract of pichia anomala and n-acetylglucosamine. In this way, low levels (e.g., less than about 0.1 or less than about 0.08, such as about 0.052) of pichia anomala extract can be used and still achieve good HA production. N-acetylglucosamine can be used as an activity enhancer for an extract of Pichia anomala to induce HA production in the skin.

The following non-limiting examples further illustrate the invention.