WO2017071821A1

WO2017071821A1 - Skin care composition and method thereof

Info

Publication number: WO2017071821A1
Application number: PCT/EP2016/025125
Authority: WO
Inventors: Judata Iskandar Darma WIBAWA; Michael David Bell
Original assignee: The Boots Company Plc
Priority date: 2015-10-30
Filing date: 2016-10-26
Publication date: 2017-05-04
Also published as: GB2544046A; GB201519207D0

Abstract

The disclosed technology relates to a composition comprising composition comprising emblica, an ester or ether derivative of ascorbic acid. The disclosed technology further relates to the use and method of improving skin lightening.

Description

SKIN CARE COMPOSITION AND METHOD THEREOF

TECHNICAL FIELD

The disclosed technology relates to a composition comprising emblica, and an ester or ether derivative of ascorbic acid. The disclosed technology further relates to the use and method of improving skin lightening. BACKGROUND OF THE INVENTION

There are a number of factors that determine skin colour, and effects of aging or other pigmentation may for instance be observed by common skin conditions that include freckles, age spots, dark spots, hyperpigmentation, discoloration, melasma, yellowing, and dark circles under the eyes. Skin colour and factors influencing it at a cellular level are believed to be as a result of the activity of melanocytes which produce the melanin pigment, distribution of blood vessels, skin thickness, the presence or absence of other pigments such as carotenoids and bilirubin. Of these factors melanin present in the skin is believed to be an important factor in skin aging, and the function of the skin is reduced due to intrinsic and extrinsic factors such as temperature, humidity, UV rays and pollutants. The production of melanin may also be affected by genetic factors, or physiological factors such as hormone secretion, or stress.

Many conventional topical lightening agents act by interfering with the action of tyrosinase, the enzyme that catalyzes the conversion of the amino acid tyrosine to DOPAquinone. EP2197413 (Johnson et al, published 23 June 2010) relates to a composition for the prevention or inhibition of free radical-induced effect on the skin and/or hair, which composition comprises at least three antioxidant agents selected from the group consisting of ginkgo extract, emblica extract, dimethylmethoxy chromanol, pine bark extract, and rosemary extract. One disclosure describes a composition comprising ginkgo extract, emblica extract and dimethylmethoxy chromanol and further containing ascorbic acid, or a salt, ester, glucoside, or glucosamine derivative thereof.

US 2008/0287533 (Gupta, published 20 November 2008) relates to esters of ascorbic acid with natural sugar lactones, and one of the sugar lactones disclosed is gluconolactone. US 2008/0287533 thus teaches combining both the ascorbic acid and the lactone to form a single molecule may be useful for treatment of skin conditions including age spots, acne, loss of cellular antioxidants, collagen loss, loss of skin pliability, loss of skin suppleness, skin wrinkles including fine lines, oxidation, damage from radiation, malfunction of matrix metalloproteases, malfunction of tyrosinases, damage from free radicals, damage from UV, dry skin, xerosis, ichthyosis, dandruff, brownish spots, keratoses, melasma, lentigines, liver spots, pigmented spots, dark circles under the eyes, skin pigmentation including darkened skin, blemishes, oily skin, warts, eczema, pruritic skin, psoriasis, inflammatory dermatoses, topical inflammation, disturbed keratinization, skin changes associated with aging, nail or skin requiring cleansers, conditioning or treatment, and hair or scalp requiring shampooing or conditioning, and combinations thereof.

SUMMARY OF THE INVENTION

It would be advantageous to have a composition that may be applied topically to provide at least one of enhanced levels of lightening, bleaching, whitening and/or depigmenting (hereinafter referred to individually and collectively as " lightening " or "lighten"). In one embodiment it may be desirable to have a topical composition with lightening agents that act to inhibit or prevent the transfer (uptake) of melanin from the melanocytes to the keratinocytes.

As used herein, the transitional term "comprising," which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, un-recited elements or method steps. However, in each recitation of "comprising" herein, it is intended that the term also encompass, as alternative embodiments, the phrases "consisting essentially of and "consisting of," where "consisting of excludes any element or step not specified and "consisting essentially of permits the inclusion of additional un-recited elements or steps that do not materially affect the basic, essential and novel characteristics of the composition, method or use under consideration. Unless otherwise indicated treat rates are on a weight basis relative to the total composition disclosed herein.

The person skilled in the art knows that a 2-hydroxycarboxylic acid described herein in a lactone form (e.g., gluconolactone) in an aqueous based system may be partially hydrolysed to its corresponding acid (e.g., gluconic acid) with the balance between the lactone form and the acid form. This is a well-known chemical equilibrium. As a result reference to 2- hydroxycarboxylic acid herein is intended to also encompass both lactone, and any equilibrium products including an acid or salt.

Unless otherwise indicated various ingredients in list of one or more compounds may be individual compounds, or in a mixture of compounds. In one embodiment the disclosed technology relates to a composition comprising emblica, an ester or ether derivative of ascorbic acid and at least one of the following options: a 2-hydroxycarboxylic acid in a form other than the acid, for example, a salt or a lactone (typically a lactone); and/or an antioxidant chosen from Mulberry (fruit or leaf extract, typically leaf extract), mangostin, Sophora, a flavonoid, hydroxyphenoxy propionic acid and a chromane.

The disclosed technology may also be defined as a composition comprising Emblica, an ester or ether derivative of ascorbic acid and at least one of the following options: an antioxidant chosen from Sophora, Mulberry (fruit or leaf extract, typically leaf extract), a flavonoid, a chromane, hydroxyphenoxy propionic acid and mangostin, or a 2-hydroxycarboxylic acid in a form other than the acid, for example, a salt or a lactone (typically a lactone).

The antioxidant may be chosen from Sophora, Mulberry (fruit or leaf extract, typically leaf extract), a chromane, hydroxyphenoxy propionic acid and mangostin.

In one embodiment the disclosed technology relates to a composition comprising emblica, an ether derivative of ascorbic acid and at least one of the following options: a 2-hydroxycarboxylic acid in a form other than the acid, for example, a salt or a lactone (typically a lactone); and/or an antioxidant chosen from Mulberry (fruit or leaf extract, typically leaf extract), mangostin, Sophora, a flavonoid, hydroxyphenoxy propionic acid and a chromane.

In one embodiment the disclosed technology relates to a composition comprising emblica, an ester or ether derivative of ascorbic acid and at least one of the following options: a 2-hydroxycarboxylic acid in a form other than the acid, for example, a salt or a lactone (typically a lactone); and/or an antioxidant chosen from Mulberry Sophora, Mulberry (fruit or leaf extract, typically leaf extract), a flavonoid, hydroxyphenoxy propionic acid and mangostin.

Typically the composition disclosed herein comprises an aqueous phase present at up to 95 wt %, or up to 90 wt % of the composition.

The composition may be in the form of a gel, cream, lotion or serum, typically a cream, serum, lotion. In one embodiment the composition may be a serum.

The composition may be an emulsion or gel.

When the composition is a gel, the composition further comprises a thickener. The composition may be a gel and the aqueous phase present at up to 95 wt % of the composition.

The composition may be an emulsion and the aqueous phase present at up to 90 wt % of the composition.

In one embodiment the composition disclosed herein comprises: emblica present at 0.01 to 2 wt % of the composition; and the ester or ether derivative of ascorbic acid is present at 0.01 to 3 wt % of the composition.

In one embodiment the composition disclosed herein comprises: emblica present at 0.05 to 1.5 wt % of the composition; and the ester or ether derivative of ascorbic acid is present at 0.05 to 2.5 wt % of the composition. In one embodiment the composition disclosed herein comprises: emblica present at 0.1 to 1 wt % of the composition; and the ester or ether derivative of ascorbic acid is present at 0.1 to 2 wt % of the composition.

In one embodiment the composition disclosed herein comprises: emblica is present at 0.1 to 0.5 wt % of the composition; and the ester or ether derivative of ascorbic acid is present at 0.1 to 1.5 wt % of the composition.

In one embodiment the disclosed technology relates to a composition comprising: emblica, an ester or ether derivative of ascorbic acid; and a 2-hydroxycarboxylic acid in a form other than the acid, for example, a salt or a lactone.

The 2-hydroxycarboxylic acid may be in the form of a lactone; and may include gluconolactone, galactonolactone, glucuronolactone, galacturonolactone, gulonolactone, ribonolactone, saccharic acid lactone, pantoyllactone, glucoheptonolactone, mannonolactone, and galactoheptonolactone. Typically the lactone may be gluconolactone.

The 2-hydroxycarboxylic acid in a form other than the acid may be present at 0.01 to 10 wt %, or 0.05 to 5 wt %, or 0.1 to 2.5 wt %, or 0.1 to 2 wt % of the composition. In one embodiment the composition disclosed herein comprises: emblica is present at

0.1 to 0.5 wt % of the composition; the ester or ether derivative of ascorbic acid is present at 0.1 to 1.5 wt % of the composition; and the 2-hydroxycarboxylic acid in a form other than the acid is present at 0.1 to 2 wt % of the composition.

In one embodiment the disclosed technology relates to a composition comprising: emblica, an ester or ether derivative of ascorbic acid; and an antioxidant chosen from Mulberry (fruit or leaf extract, typically leaf extract), mangostin, Sophora, a flavonoid, hydroxyphenoxy propionic acid (i.e., Radianskin®) and a chromane.

In one embodiment the disclosed technology relates to a composition comprising: emblica, an ester or ether derivative of ascorbic acid; and an antioxidant chosen from Mulberry (fruit or leaf extract, typically leaf extract), or Sophora.

In one embodiment the disclosed technology relates to a composition comprising: emblica, a metal ascorbyl phosphate (such as sodium ascorbyl phosphate), and an antioxidant chosen from Mulberry (fruit or leaf extract, typically leaf extract), mangostin, Sophora, a flavonoid, hydroxyphenoxy propionic acid and a chromane, wherein the composition is in the form of a water-in-silicone emulsion. The antioxidant may be Mulberry (fruit or leaf extract, typically leaf extract), or Sophora, typically Mulberry (fruit or leaf extract, typically leaf extract). In one embodiment the antioxidant may not include Sophora and/or kiwi extract.

In one embodiment the disclosed technology relates to a composition comprising: emblica, a metal ascorbyl phosphate (such as sodium ascorbyl phosphate), and an antioxidant chosen from Mulberry (fruit or leaf extract, typically leaf extract), mangostin, Sophora, a flavonoid, hydroxyphenoxy propionic acid and a chromane, wherein the composition is in the form of an oil-in-water emulsion. The antioxidant may be Mulberry (fruit or leaf extract, typically leaf extract), or Sophora, typically Mulberry (fruit or leaf extract, typically leaf extract).

In one embodiment the disclosed technology relates to a composition comprising: emblica, a 2-hydroxycarboxylic acid in forms other than the acid, for example, a salt or a lactone, and either ascorbyl glucoside, or ether derivative of ascorbic acid (such as an O- substituted ascorbic acid or derivative thereof), wherein the composition is in the form of an oil-in-water emulsion.

In one embodiment the disclosed technology relates to the cosmetic use of a composition disclosed herein (typically a skin care composition).

In one embodiment the disclosed technology relate to a method of imparting a benefit of at least one of lightening, bleaching, whitening and/or depigmenting of skin comprising supplying/administering to skin (typically human skin) the composition disclosed herein.

In one embodiment the disclosed technology relate to the use of the composition disclosed herein to enhance levels of at least one of lightening, bleaching, whitening and/or depigmenting of skin.

The use and method disclosed herein are known to the skilled person as not encompassing therapeutic or medical treatment i.e., the disclosed use or method relate to a non- therapeutic use or method.

DETAILED DESCRIPTION OF THE INVENTION

The disclosed technology provides a composition, methods and uses as disclosed above. Lightening Agent

The composition disclosed herein comprises emblica; and it may be present at 0.001 to 10 wt %, or 0.01 to 5 wt %, or 0.05 to 2 wt %, or 0.1 to 1 wt % of the composition. In one embodiment emblica may be present at 0.1% to 0.5 wt % of the composition.

In one embodiment the lightening agent may be a mixture of ingredients chosen from: emblica, and an antioxidant chosen from Sophora, Mulberry (fruit or leaf extract, typically leaf extract), a flavonoid, a chromane (such as dimethylmethoxy chromanol), hydroxyphenoxy propionic acid and mangostin. The antioxidant it may be present at 0.001 to 10 wt %, or 0.01 to 5 wt %, or 0.05 to 2 wt %, or 0.1 to 1 wt % of the composition. In one embodiment antioxidant may be present at 0.1% to 0.5 wt % of the composition. The composition disclosed herein may comprise 0.1 % to 0.5 wt % of emblica, and 0.1% to 0.5 wt % of an antioxidant chosen from Mulberry (fruit or leaf extract, typically leaf extract), mangostin, Sophora, a flavonoid, hydroxyphenoxy propionic acid and a chromane.

When the composition comprises emblica and two or more antioxidants, each antioxidant may be present at 0.1 to 5 wt % of the composition. In one embodiment the lightening agent may be a mixture of ingredients chosen from: emblica and Mulberry (fruit or leaf extract, typically leaf extract), optionally in the presence of Sophora.

In one embodiment the lightening agent may be a mixture of ingredients chosen from: emblica and Sophora, optionally in the presence of Mulberry (fruit or leaf extract, typically leaf extract).

In one embodiment the lightening agent may be a mixture of emblica, Sophora, and Mulberry (fruit or leaf extract, typically leaf extract).

The emblica may be emblica officinalis, typically comprising over 40% by weight (typically 50-80 wt %) of Emblicanin A. Emblicanin B, Pedunculagin and Punigluconin, and not more than about 1% by weight of flavonoids.

The emblica may be Phyllanthus emblica.

The Sophora may be an extract of a small tree, and shrub in the pea family Fabaceae. The Sophora may be a Sophora Angustifolia Root Extract, a Sophora flavescens root extract, a Sophora Alopecuroides Extract, or Sophora japonica extract.

The Sophora Angustifolia Root Extract may be an extract of the roots of the Chinese Sophora, Sophora angustifolia, or Leguminosae.

In one embodiment Sophora is derived from Sophora Angustifolia Root Extract. Typically the emblica may be Phyllanthus emblica and Sophora is derived from Sophora

Angustifolia Root Extract.

The disclosed technology may comprise Mulberry (fruit or leaf extract, typically leaf extract), emblica in the form of Phyllanthus emblica and Sophora derived from Sophora Angustifolia Root Extract. The flavonoid species is believed to have antioxidant performance, and be an antioxidant plant polyphenolic agent. By the term antioxidant plant polyphenolic agent we mean a plant extract, or derivative thereof, comprising flavonoid species, including flavones, flavonols, flavanones, flavanols anthocyanidins and isoflavonoids; phenolic acid species; stilbenes; lignans and mixtures thereof, which provide an antioxidant benefit. Antioxidant benefit is measured using the total antioxidant capacity (TAC) assay described herein. Plants provide a rich source of polyphenolic agents, and are therefore an efficient source of said antioxidants. Similar actives may be prepared synthetically and as such are analogues of said plant polyphenolic agents.

Antioxidant polyphenolic agents may include extracts from plants chosen from Mulberry (e.g. morus alba), Ginseng (e.g. Panax ginseng), Raspberry, Oregano (e.g. origanum vulgare), Green tea (e.g. green leaves of camellia sinensis), White tea (e.g. camellia sinensis), Blueberry extract (e.g. vaccinium cyanococcus), French maritime pine bark (e.g. pinus pinaster, sold under the tradename Pycnogenol) , Rosemary (e.g. rosmarinus officialis), Grape, including grape seed (e.g. vitis vinifera), Fennel (e.g. foeniculi fructus), Caragana sinica, Marjoram (e.g. origanum majorana), Crocus (e.g. crocus sativus), Apple (e.g. malus domestica), Coffee, Green coffee, Cherry (e.g. prunus avium), Snow algae (e.g. chlamydomonas nivalis), Gingko (e.g. Gingko biloba), Moringa (e.g. moringa oleilera), Ginger (e.g. zingiberaceae), Magnolia (e.g. magnolioideae virginiana), Edelweiss (e.g. leontopodium alpinium), White lotus (e.g. nymphaea alba), Turmeric root, Marshmallow (e.g. althaea officianlis), Burdock (e.g. arctium lappa) , Bilberry (e.g. vaccinium myrtillus), Cranberry (e.g. vaccinium oxycoccus), Pomegranate nectar (e.g. Punica granatum), Sage (e.g. salvia officinalis), Thyme (e.g. thymus vulgaris), Sunflower (e.g. helianthus annuus), wild carrot (e.g. daucus carota), Hop (e.g. humulus lupulus), Witch Hazel (e.g. hamamelis), Oak (e.g. Quercus), Camellia (e.g. theacea), Red clover (e.g. tritolium pratense), Flax (e.g. linium usitatissimum), lemon (e.g. citrus limon), birch (e.g. betula), cornflower, (e.g. centaurea cyanus), geranium, polygonum, soy (e.g. glycine max), and mixtures thereof.

In one embodiment the antioxidant polypenolic agent may be an extract from a plant chosen from mulberry, ginseng, grape, oregano, sage, sunflower, maritime pine bark, rosemary, marjoram, crocus, wild carrot, hop, coffee, green coffee, witch hazel, oak, camellia, red clover, flax, ginger, magnolia, edelweiss, burdock and mixtures thereof.

In one embodiment the antioxidant may be flavonoid, and derived form a plant or extract thereof chosen from mulberry, Panax ginseng, grape, oregano, maritime pine bark, rosemary, hop, green tea (EGCG), green coffee, witch hazel, red clover, ginger, magnolia, ginkgo, and a chromane.

In one embodiment the antioxidant may be flavonoid, and derived from a plant or extract thereof chosen from mulberry, grape, oregano, maritime pine bark, hop, green tea (EGCG), green coffee, witch hazel, red clover, ginger, magnolia, ginkgo, and a chromane.

In one embodiment the antioxidant may be flavonoid, and derived form a plant or extract thereof chosen from grape, oregano, maritime pine bark, hop, green tea (EGCG), green coffee, witch hazel, red clover, ginger, magnolia, ginkgo, and a chromane.

In one embodiment the antioxidant may be flavonoid, and derived form a plant or extract thereof chosen from grape, oregano, maritime pine bark, hop, green tea (EGCG), green coffee, red clover, ginger, magnolia, ginkgo, and a chromane.

In one embodiment the antioxidant may be flavonoid, and derived from a plant or extract thereof chosen from grape, oregano, maritime pine bark, hop, green tea (EGCG), green coffee, red clover, ginger, magnolia, and ginkgo.

Active polyphenolic species sourced from the above list of plants include those chosen from apigenin, luteolin, quercetin, kaempferol, naringenin, hesperetin, catechin, gallocatechin, cyanidin, pelargonidin, daidzein, genistein, caffeic acid, chlorogenic acid, rosmarinic acid, gallic acid, resveratrol, ferulic acid, epigallocatechin gallate, piceatannol, secoisolariciresinol, isotaxiresinol, Miyabenol c, Luteolin and mixtures thereof.

The amount of antioxidant (typically from plant polyp heno lie agents) used in the present invention are expressed as dry weights of the extract, as understood by a man skilled in the art. The antioxidant may be present at 0.005 to 10 wt %, or 0.01 to 7 wt %, or 0.01 to 5 wt % of the composition.

When present the chromane may be chosen from: methyl, di-, tri- and tetra- C1-C6 alkyl, C1-C6 alkoxy chromanol; pentamethyl chromanol, methyl, di, tri and tetra C1-C6 alkyl, C1-C6 alkoxy chromanyl C14-C20 ester and mixtures thereof.

Typically the chromane may be chosen dimethyl methoxy chromanol, tetramethyl methoxy chromanol, pentamethyl chromanol, dimethyl methoxy chomanyl palmitate, dialkyl methoxy chomanyl myristate, dimethyl methoxy chromanyl stearate, dimethyl methoxy chomanyl oleate, dimethyl methoxy chomanyl linoleate and mixtures thereof.

In one embodiment the chromane may be dimethyl methoxy chromanol (commercially available under the tradename Lipochroman 6 as sold by Lipotec). Derivative of Ascorbic Acid

The disclosed technology may include an ester or ether derivative of ascorbic acid. The ester or ether derivative of ascorbic acid may be present at 0.001 to 5 wt %, or 0.01 to 3 wt %, or 0.1 to 2 wt % of the composition. In one embodiment the ester or ether derivative of ascorbic acid may be present at 0.1 to 1.5 wt % of the composition. The ester derivative of ascorbic acid may include an organic ester derivative such as ascorbyl glycoside, or an inorganic ester such as a metal ascorbyl phosphate.

The metal ascorbyl phosphate may include alkali or alkaline earth metal salts such as sodium, potassium, lithium, calcium or magnesium. Typically the metal ascorbyl phosphate may include sodium ascorbyl phosphate, magnesium ascorbyl phosphate, or potassium ascorbyl tocopheryl phosphate.

Potassium ascorbyl tocopheryl phosphate i.e., a salt of both vitamin E (tocopherol) and vitamin C (ascorbic acid).

The ether derivative of ascorbic acid may include an O-substituted ascorbic acid or derivative thereof. The O-substituted ascorbic acid or derivative thereof may be an 0-alk(en)yl ascorbic acid or derivative thereof.

As used herein "alk(en)yl" is intended to mean alkyl or alkenyl (typically alkyl).

The alk(en)yl may be acyclic or cyclic, typically acyclic. The acyclic group may be linear or branched, typically linear.

Typically the O-substituted ascorbic acid or derivative thereof is an O-alkyl ascorbic acid, or derivative thereof.

The O-substituted ascorbic acid, or derivative thereof is known in the art, and described in EP Patent application EP2722043 Al, and US 2014/0155633 (both Lin et al, Applicant Corum).

In one embodiment the O-substituted ascorbic acid, or derivative thereof may be represented by the formula:

wherein R¹ and R² groups may independently be H, CI -20 alkyl, C3-20 cycloalkyl, CI -20 alkoxy, C2-20 acyl, C6-20 aryl, CI -20 heterocyclic aromatic, CI -20 heterocyclic non-aromatic, or C3-20 cycloalkenyl.

The O-substituted ascorbic acid or derivative thereof may have a substituted group that may be hydrocarbon in nature i.e., composed on carbon and hydrogen. In one embodiment R¹ and R² groups may independently be H, CI -20 alkyl, C3-20 cycloalkyl, C6-20 aryl, or C3-20 cycloalkenyl. In one embodiment the O-substituted ascorbic acid may be 3 -alkyl ascorbic acid, or mixtures thereof. Typically the alkyl group may be a Cl-20, or Cl-10, or C2-8, or C2-4.

Typically the O-substituted ascorbic acid may be 3-ethyl ascorbic acid. In one embodiment the ester or ether derivative of ascorbic acid may be ascorbyl glycoside, an O-substituted ascorbic acid or derivative thereof (typically 3-ethyl ascorbic acid), or sodium ascorbyl phosphate.

When the ester or ether derivative of ascorbic acid is in the form of an inorganic ester such as a metal ascorbyl phosphate, the composition may typically be a water-in-silicone or an oil-in-water, or water-in-in-oil emulsion, typically a water-in-silicone emulsion.

When the ester or ether derivative of ascorbic acid is in the form of an organic ester derivative, or an ether, the composition may typically be a gel or an oil-in-water emulsion.

Other Ingredients

The composition disclosed herein may optionally further comprise other ingredients. The other ingredients include Hibiscus, a peptide, a matrix metalloproteinase inhibitor, a whitening agent, a skin conditioning agent, a salicyclic acid compound, a sunscreen agent, preservatives thickeners, viscosity modifying agents, and/or gelling agents sequestering agents, wax, diluents, carriers, propellants perfumes, or pH adjusting agents.

In one embodiment the composition disclosed herein further comprises one or more of Hibiscus, a peptide, a matrix metalloproteinase inhibitor, a whitening agent.

The Hibiscus may be Hibiscus sabdariffa, Hibiscus rosa sinensis or Hibiscus Abelmoschus (may also be known as Abelmoschus moschatus). All three Hibiscus plants are known to form extracts used in cosmetic compositions. The Hibiscus may be in the form of an extract.

Peptides are defined as compounds comprising an uninterrupted sequence of amino acids. Typically the peptides are of natural origin. A dipeptide comprises an uninterrupted sequence of two amino acids. Amino acids, as employed herein, include and encompass all of the naturally occurring amino acids, either in D or L configuration. Amino acids are commonly indicated with reference to the conventional three letter code and the sequence is read from left to right. The composition of the disclosed technology may comprise a dipeptide chosen from acetyl dipeptide 1 cetyl ester, acetyl dipeptide 3 aminohexanoate, azelaoyl bisdipeptide 10, coumaroyl dipeptide 3, dicetyl dipeptide 9, dipeptide diamino butyroyl benzylamide diacetate, dipeptide 1, dipeptide 10, dipeptide 11, dipeptide 12, dipeptide 15, dipeptide 16, dipeptide 17, dipeptide 18, dipeptide 19, dipeptide 2, dipeptide 20, dipeptide 3, dipeptide 4, dipeptide 5, dipeptide 6, dipeptide 7, dipeptide 8, dipeptide 8 HCL, dipeptide 9, hexanoyl dipeptide 3 norleucine acetate, methyl undecylenoyl dipeptide 16, nicotinoyl dipeptide 22, nicotinoyl dipeptide 23, nicotinoyl dipeptide 24, nicotinoyl dipeptide 26, oleoyl dipeptide 15, palmitoyl dipeptide 10, palmitoyl dipeptide 13, palmitoyl dipeptide 17, palmitoyl dipeptide 5 diaminobutyroyl hydroxythreonine, palmitoyl dipeptide 5 diaminohydroxybutyrate, palmitoyl dipeptide 7 and mixtures thereof.

In one embodiment the composition of the disclosed technology may comprise a tripeptide, or mixtures thereof. The tripeptide may be naturally occurring or of synthetic origin. Suitable tripeptide compounds include tripeptide 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 ,29, 30, 31, 32, 33, 34, 35, 36 ,37, 38, 39, 40, 41, 42, 43, 44, 45, 46, derivatives thereof, and mixtures thereof. The tripeptide comprise one or more His-based tripeptides.

The compositions of the disclosed technology may further comprise a tetrapeptide. The tetrapeptide may be one or more rigin-based tetrapeptides, one or more ALAMCAT- tetrapeptides or mixtures thereof. The tetrapeptide may be naturally occurring or of synthetic origin. Suitable tetrapeptides for use in the present composition include those chosen from tetrapeptide 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 34, 35, derivatives thereof and mixtures thereof.

Rigin-based tetrapeptides of the disclosed technology may be based on the structure Gly-Gln-Pro-Arg (Rigin) and include its analogs and derivatives thereof. Rigin is a typical tetrapeptide.

The compositions of the disclosed technology may further comprise a pentapeptide, derivatives of thereof, and mixtures thereof. As used herein, "pentapeptide" refers to both the naturally occurring pentapeptide and synthesized pentapeptide. Also useful herein are naturally occurring and commercially available compositions that comprise pentapeptides. Suitable pentapeptides are those chosen from pentapeptide 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 28, 29, 30, 31, 33, 34, 35, 36, 38, 39, derivatives thereof and mixtures thereof.

The peptide when present in the composition disclosed herein may be present at 0 or 0.01% to 20%, or 0.05% to 15%, or 0.05 to 10 wt % of the composition.

Matrix Metalloproteinase Inhibitor (MMPi)

The term "matrix metalloproteinase inhibitor" relates to all molecule and/or plant or bacterial extracts having an inhibitory activity on at least one of the matrix metalloproteinases expressed, synthetized, or activated by or in the skin. The family of the matrix metalloproteinases is formed of several well-defined groups on the basis of their resemblance regarding structure and substrate specificity (Woessner J. F., Faseb Journal, vol. 5, 1991, 2145).

The MMPi may be present at a level of from 0 or 0.01% to 10%, or 0.1% to 5% or 0.25% to 2.5%, or 0.5% to 1% by weight of the composition.

Skin Conditioning Agent

The composition of the present invention may optionally comprise a skin conditioning agent. The skin conditioning agents may be chosen fromhumectants, emollients, moisturisers, or mixtures thereof. Where present, the skin conditioning agent may be present from 0 or 0.01 % to 20%, or 0.1% to 10%, or 0.5% to 7% by weight of the composition.

The skin conditioning agents may be chosen from guanidine, urea, glycolic acid and glycolate salts, salicylic acid, lactic acid and lactate salts, aloe vera, shea butter, polyhydroxy alcohols, such as sorbitol, mannitol, xylitol, erythritol, glycerol, hexanetriol, butanitriol, (di) propylene glycol, butylene glycol, hexylene glycol, polyethylene glycol, sugars (e.g. fructose, glucose, xylose, honey, mannose, xylose), gluconodeltalactone, and starches and their derivatives, pyrrolidone, carboxylic acid, hyaluronic acid and salts thereof, lactamide monoethanolamine, acetamide monoethanolamine, panthenol, allantoin and mixtures thereof.

Typically the skin conditioning agent is chosen from glycerine, arabinoglactan, butylene glycol, hyaluronic acid, shea butter, propylene glycol, ethylhexyl glycerine, hyaluronate and mixtures thereof.

Salicylic Acid Compound

The compositions disclosed herein may optionally comprise a salicylic acid compound, its esters, its salts, or combinations thereof. In one embodiment of the composition disclosed herein comprises a salicylic acid compound at 0 or 0.0001%> to 25%, or 0.001%> to 15%, or 0.01% to 10%, or 0.1% to 5%, and or 0.01% to 2%, by weight of the composition, of salicylic acid. In one embodiment the salicylic acid compound is salicylic acid.

Sunscreen

The composition of the present invention may optionally comprise a sunscreen component. The sunscreen may comprise organic or inorganic sun filters or a combination of the two. Suitable inorganic sunfilters include those chosen from microfine titanium dioxide, and microfine zinc oxide, and mixtures thereof. Suitable organic sunscreens include those chosen from: a) p-aminobenzoic acids, their esters and derivatives (for example, 2-ethylhexyl p-dimethylaminobenzoate), b) methoxycinnamate esters (for example, 2-ethylhexyl p-methoxycinnamate, 2-ethoxyethyl p- methoxycinnamate or a, p-di- (p-methoxycinnamoyl)-a'- (2-ethylhexanoyl)-glycerin, c) benzophenones (for example oxybenzone), d) dibenzoylmethanes such as 4- (tert-butyl)-4'- methoxydibenzoylmethane, e) 2-phenylbenzimidazole-5 sulfonic acid and its salts, f) alkyl-ss, ss-diphenylacrylates for example alkyl a-cyano-ss, ss-diphenylacrylates such as octocrylene, g) triazines such as 2,4,6-trianilino- (p-carbo-2-ethyl-hexyl-l-oxi)-l, 3,5 triazine, h) camphor derivatives such as methylbenzylidene camphor and i) mixtures thereof. Other sunscreen ingredients include those chosen from homosalate, Ethylhexyl salicylate, Diethylhexylbutamido triazone, Bis-ethylhexyloxyphenol methoxyphenyl triazine, Diethylamino hydroxybenzoyl hexyl benzoate, Butyl methoxydibenzoylmethane, Methylene bis-benzotriazoyl tetramethylbutylphenol, Polysilicone-15 and mixtures thereof. A sunscreening agent may be present from 0 to 10 %, or 0.1 to 10% by weight of the composition. Other Optional Ingredients

Preservatives may be added to the composition such as benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, 2-bromo2-nitropropane-l,3-diol (bronopol, which is available commercially under the trade name Myacide ®, benzyl alcohol, diazolidinyl urea, imidazolidinyl urea, methyl paraben, phenoxy ethanol, ethyl paraben, propyl paraben, sodium methyl paraben, sodium dehydroacetate, polyhexamethylenebiguanide hydrochloride, isothiazolone and sodium propyl paraben and mixtures thereof, suitably in an amount of from 0.01 % to 10%) by weight of the composition.

Sequestering agents may be added to the composition, such as ethylenediamine tetraacetic acid and salts thereof, typically in an amount of from 0 or 0.005% to 0.5% by weight of the composition.

The composition may also include waxes such as cocoa butter suitably in an amount of from 0.1% to 10% by weight of the composition.

The composition may also comprise suitable, cosmetically acceptable diluents, carriers and/or propellants such as dimethyl ether. The composition may also include pearlising agents such as stearic monoethanolamide and/or mica, suitably in an amount of from 0 or 0.01% to 10% by weight of the composition. Perfumes may be added suitably in an amount of from 0 or 0.01% to 2% by weight of the composition, as may water soluble dyes such as tartrazine, suitably in an amount of from a trace amount such as 0 or lxl 0^"5 % to 0.1 % by weight of the composition.

The composition may also include pH adjusting agents such as sodium hydroxide, amino methyl propanol, triethanolamine, suitably in an amount of from 0 or 0.01 % to 10% by weight of the composition. The composition may be buffered by means well known in the art, for example by use of buffer systems comprising succinic acid, citric acid, lactic acid, and acceptable salts thereof, phosphoric acid, mono-or disodium phosphate and sodium carbonate. Suitably, the composition may have a pH between 3 and 10, between 4 and 8, or between 4.5 and 6.5.

In one embodiment the composition of the disclosed technology does not include MMP compounds that comprise one hydroxyaryl or polyhydroxyaryl compound, or cyclic compounds having a cyclic group based upon a compound comprising a pyran, a lactam, or a piperidine constituent.

In one embodiment the composition of the disclosed technology does not contain a ascorbic acid derivative chosen from sodium ascorbyl phosphate, ascorbyl glycoside, L- ascorbic acid, ascorbyl palmitate, retinyl ascorbate, tetrahexyldecyl ascorbate, or magnesium ascorbyl phosphate.

In one embodiment the composition of the disclosed technology does not contain chromane and/or ginkgo.

Gel

When in the form of a gel, the composition disclosed herein may contain 0.1 to 10 wt %, or 0.5 wt % to 5 wt %, or 0.5 wt % to 3 wt % of a thickener such as a viscosity modifying agent and/or gelling agent, and may be typically a polymeric thickener.

A thickener, viscosity modifying agent and/or gelling agent may be added to the composition, such as acrylic acid polymers e. g. available commercially under the trade name Carbopol® or Ultrez® (both Lubrizol ), or a taurate copolymer such as acryloyi methyl taurate- vinyipyrroiidone copolymers, or hydroxyethylacrylatc sodium acryloyidimethyl taurate copolymers, or modified celluloses e. g. h yd rax y eth y 1 eel 1 u lose available commercially under the trade name Natrosol® (Hercules) or hydroxypropylmethyl cellulose, amine oxides, block polymers of ethylene oxide and propylene oxide (for example, those available from BASF Wyandotte under the trade name' luronic"®), PVM, MA, or a decadiene crosspolymer (available under the trade name Stabilez® 60), ethoxylated fatty alcohols, salt (magnesium chloride, sodium chloride), Aristoflex®AVC (Clariant), phthalic acid amide, xanthan gum, starch, or modified starch (such as a metal salt of starch e.g., aluminum salt of the reaction product of 1-octenyisuccinic anhydride with starch), sodium polyacrylate, polyvinyl alcohols, fatty alcohols and alkyl galactmanans available under the trade name N-Hance® from Hercules.

The gel may comprise:

50 wt % to 95 wt % water and 0.1 to 10 wt % of a thickener, or

60 wt % to 95 wt % water, and 0.5 wt % to 5 wt % of a thickener, or

70 wt % to 90 wt % of water; and 0.5 wt % to 3 wt % of a thickener.

Emulsion The emulsion disclosed herein may be a water-in-oil, oil-in- water, or water-in-silicone composition, typically oil-in-water composition.

The emulsion may be an oil-in-water emulsion, or a water-in-silicone oil emulsion, typically an oil-in-water emulsion.

The emulsion may comprise an oil phase and have an aqueous phase content of 30 to 85 wt %, or 50 to 80 wt %, or 60 to 75 wt % of the composition.

The aqueous phase may contain water present at 40 to 80 wt %, or 50 to 75 wt %, or 60 to 75 wt % of the composition.

The emulsion may comprise an oil phase having 15 to 70 wt %, or 30 to 50 wt %, or 25 to 40 wt % of the composition. The emulsion may be an oil-in-water composition comprising 15 to 70 wt % of an oil phase; and 30 to 85 wt % of an aqueous phase.

The emulsion may be an oil-in-water composition comprising 25 to 40 wt % of an oil phase; and 60 to 75 wt % of an aqueous phase.

The emulsion may be in the form of a water-in-silicone emulsion, and the water phase may be present at 30 to 85 wt % of an aqueous phase; and silicone present at 15 to 70 wt % of a silicone phase. The emulsion may be in the form of a water-in-silicone emulsion, and the water phase may be present at 60 to 75 wt % of an aqueous phase; and silicone present at 25 to 40 wt % of a silicone phase.

If the composition disclosed herein is in the form of a water-in-silicone composition the oil phase may be provided by any suitable silicate, dimethiconols, silicone elastomer and mixtures thereof (typically a silicone elastomer).

Typically the silicone oil phase may be formed from an organopolysiloxane. The organopolysiloxane may be chosen from one or more of a polyalkylsiloxane, alkyl substituted dimethicone, cyclomethicone, trimethylsiloxysilicate. dimethiconol, polyalkylaryl siloxane, and mixtures thereof. The polyalkylsiloxane may be for example a cyclomethicone, or dimethicone, typically a dimethicone.

A water-in-silicone composition disclosed herein may include an emulsifying crosslinked organopolysiloxane elastomer, a non-emulsifying crosslinked organopolysiloxane elastomer, or a mixture thereof. The term "non-emulsifying," as used herein, defines crosslinked organopolysiloxane elastomers from which polyoxyalkylene units are absent. The elastomers may include dimethyl polysiloxanes crosslinked by Si-H sites on a molecularly spherical MQ resin. Emulsifying crosslinked organopolysiloxane elastomers include the crosslinked polymers described in US Patents 5,412,004; 5,837,793; and 5,811,487. The emulsifying elastomer comprised of dimethicone copolyol crosspolymer (and) dimethicone is commercially available from Shin Etsu under the trade name KSG-21. The non-emulsifying elastomers may include dimethicone crosspolymers. Such dimethicone crosspolymers are supplied by a variety of suppliers including Dow Corning (EL9240). Other dimethicones crosspolymer are available from General Electric (SFE 839), Shin Etsu (KSG-15, 16, 18 [dimethicone/phenyl vinyl dimethicone crosspolymer]), and Grant Industries (GRANSIL™ line of elastomers). Cross-linked organopolysiloxane elastomers useful in the present invention and processes for making them are further described in US Patents 4,970,252; 5,760,116; and 5,654,362. Commercially available elastomers typical for use herein are Dow Coming's 9040 silicone elastomer blend, Shin Etsu's KSG-21, and mixtures thereof. The term "ester oil" means an oil that is liquid at room temperature (25 °C.) comprising at least one ester functional group. The ester oil used herein is chosen, for example, from monoesters.

The ester oil may, for example, be chosen from, the monoesters of formula R 'COOR² wherein R¹ may be selected from, linear and branched hydrocarbon-based chains comprising from 4 to 30, or 6 to 24, or 7 to 20 carbon atoms carbon atoms, and R² may be chosen, from branched hydrocarbon-based chains comprising from 3 to 40 carbon atoms, such as from. 10 to 30 carbon atoms and further such, as from 16 to 26 carbon atoms.

Examples of the ester oils that may be mentioned include isodecyi neopentanoate; isocetyl octanoate; isonony! isononanoate, isodecyi isononanoate, tridecy! isononanoate; hexyi laii rate. 2-hexyldccyl lauratc; isopropyi myristate, isocetyl myristate, isotridecyl myristate, 2- octyldodecyl myristate; isopropyi palmitate, 2-ethylh.exyl palmitate, isooctyl palmitate, isocetyl palmitate, isodecyi palmitate, isostearyl palmitate, 2-octyidecyi palmitate; isopropyi isostearate, 2-octyidodecyl stearate, isostearyl isostearate, and 2-octyldodecyl erucate.

The ester oil may be present in the emulsion disclosed herein in an amount ranging, for example, from 0 to 20 wt %, or 0.1 to 15 wt %, or 1 to 10 wt % of the composition.

EXAMPLES

Comparative Example 1 (CE1): is a water-in-silicone composition comprising 0.75 wt % of sodium ascorbyl phosphate, 0.05 wt % sophora, and 0.35 wt % emblica.

Inventive Example 1 (EX1): is a water-in-silicone composition comprising 1.1 wt % of sodium ascorbyl phosphate, 0.3 wt % mulberry extract, and 0.5 wt % emblica.

Comparative Example 2 (CE2): is an oil-in-water composition comprising 1.1 wt % ascorbyl glycoside, 3 wt % gluconolactone, and 0.1 wt % emblica. Inventive Example 2 (EX2): is an oil-in-water composition comprising 1.1 wt % ascorbyl glycoside, 3 wt % gluconolactone, 3 wt % sophora, and 0.5 wt % emblica.

Testing Each example is evaluated by in an 8 week in vivo split face single blinded randomised controlled design on women aged 25 - 55 years old presenting with Fitzpatrick skin phototypes III or IV, with uneven skin tone of differing severity. Each example is applied twice a day over the designated randomised half face. Skin lightening efficacy is evaluated objectively by determination of the L* and a* colour parameters using the Chromameter colorimeter. The percentage change for CIE Colour Model axis ITA*, L* and a* are reported below for each example. Typically better values are recorded for examples having a larger negative a* percentage (indicative of the change in colour on the green to red axis); and a larger positive percentage change in L* (indicative of colour change on the white to black axis) and ITA* (measure of brown skin).

The results indicates that the compositions disclosed herein and exemplified by EX1 and EX2 have improved lightening effect relative to comparative examples CEl and CE2 respectively.

Claims

CLAIMS We claim:

1. A composition comprising Emblica, an ester or ether derivative of ascorbic acid and at least one of the following options: an antioxidant chosen from Sophora, Mulberry (fruit or leaf extract, typically leaf extract), a flavonoid, a chromane, hydroxyphenoxy propionic acid and mangostin, or a 2-hydroxycarboxylic acid in a form other than the acid, for example, a salt or a lactone (typically a lactone).

2. The composition of claim 1, wherein the composition comprises an aqueous phase present at up to 95 wt %, or up to 90 wt % of the composition.

3. The composition of any preceding claim, wherein emblica; is present at 0.001 to 10 wt %, or 0.01 to 5 wt %, or 0.05 to 2 wt %, or 0.1 to 1 wt % of the composition.

4. The composition of any preceding claim, wherein the ester or ether derivative of ascorbic acid may be present at 0.001 to 5 wt %, or 0.01 to 3 wt %, or 0.1 to 2 wt % of the composition.

5. The composition of any preceding claim, wherein emblica is present at 0.1 to 1 wt % of the composition; and the ester or ether derivative of ascorbic acid is present at 0.1 to 2 wt % of the composition.

6. The composition of any preceding claim, wherein emblica is present at 0.1 to 0.5 wt % of the composition; and the ester or ether derivative of ascorbic acid is present at 0.1 to 1.5 wt % of the composition.

7. The composition of claim 1, wherein emblica is present at 0.1 to 0.5 wt % of the composition; the ester or ether derivative of ascorbic acid is present at 0.1 to 1.5 wt % of the composition; and the 2-hydroxycarboxylic acid in a form other than the acid is present at 0.1 to 2 wt % of the composition.

8. The composition of claim 2, wherein the composition comprises emblica, the 2-hydroxycarboxylic acid in forms other than the acid, and either ascorbyl glucoside, or ether derivative of ascorbic acid (such as an O-substituted ascorbic acid or derivative thereof), wherein the composition is in the form of an oil-in- water emulsion.

9. The composition of any preceding claim, wherein the ether derivative of ascorbic acid is an O-substituted ascorbic acid, or derivative thereof represented by the formula:

wherein R¹ and R² groups are independently H, CI -20 alkyl, C3-20 cycloalkyl, CI -20 alkoxy, C2-20 acyl, C6-20 aryl, CI -20 heterocyclic aromatic, CI -20 heterocyclic non-aromatic, or C3- 20 cycloalkenyl.

10. The composition of any preceding claim 1 to 7, wherein the ester derivative of ascorbic acid is ascrobyl glycoside, or a metal ascorbyl phosphate.

11. The composition of claim 10, wherein the metal ascorbyl phosphate is chosen from sodium ascorbyl phosphate, magnesium ascorbyl phosphate, or potassium ascorbyl tocopheryl phosphate.

12. The composition of any preceding claim 1 to 11 comprising: emblica, a metal ascorbyl phosphate (such as sodium ascorbyl phosphate), and an antioxidant chosen from Mulberry (fruit or leaf extract, typically leaf extract), mangostin, Sophora, a flavonoid, hydroxyphenoxy propionic acid and a chromane, wherein the composition is in the form of a water-in-silicone emulsion.

13. The composition of any preceding claim 1-9, and 12-13, wherein the composition comprises emblica, an ether derivative of ascorbic acid and at least one of the following options: a 2-hydroxycarboxylic acid in a form other than the acid, for example, a salt or a lactone (typically a lactone); and/or an antioxidant chosen from Mulberry (fruit or leaf extract, typically leaf extract), mangostin, Sophora, a flavonoid, hydroxyphenoxy propionic acid and a chromane.

14. A method of imparting a benefit of at least one of lightening, bleaching, whitening and/or depigmenting of skin comprising supplying/administering to skin a composition of any preceding claim 1 to 13.

15. The use of the composition of any preceding claim 1 to 13 to enhance levels of at least one of lightening, bleaching, whitening and/or depigmenting of skin.