GB2543822A - Skin care composition and method thereof - Google Patents

Abstract

Skin care compositions comprising O-substituted ascorbic acid derivatives, a matrix metalloproteinase inhibitor, and hibiscus and/or a peptide (I) A composition comprising: an O-substituted ascorbic acid or derivative thereof; a matrix metalloproteinase inhibitor; and hibiscus and/or a peptide, wherein the composition comprises an aqueous phase present at up to 95 wt% or up to 90 wt% of the composition is provided. Preferably the O-substituted ascorbic acid derivative is represented by formula (I) wherein R1 and R2 are independently H, C1-20alkyl, C3-20cycloalkyl, C1-20alkoxy, C2-20acyl, C6-20aryl, C1-20heterocyclic aromatic, C1-20heterocyclic non-aromatic or C3-20cycloalkenyl, in particular the O-substituted ascorbic acid derivative is 3-ethyl ascorbic acid. Preferably the matrix metalloproteinase inhibitor is selected from N-acetyl cysteine, glutathione, 2-flurildioxime, vitamin C (other than the O-substituted ascorbic acid or derivative thereof), hydrolysed rice protein, alfalfa extract, white lupin, zizyphus jujube extract, kudzu extract, vitis vinifera extract, Oenothera biennis extract or anogeissus leiocarpus extract and mixtures thereof. The composition may be in the form of an oil-in-water composition comprising 30 to 85 wt% of an aqueous phase, and 15 to 70 wt% of an oil phase. Preferably the composition is a water-in-silicone oil emulsion wherein the silicone oil is preferably a silicone elastomer. The composition is preferably used in a method of decreasing or preventing wrinkles or fine lines, skin sagging, or increasing skin firmness.

Description

SKIN CARE COMPOSITION AND METHOD THEREOF TECHNICAL FIELD

The disclosed technology relates to a composition comprising: an O-substituted ascorbic acid or derivative thereof; a matrix metalloproteinase inhibitor; and hibiscus or a peptide, wherein the composition comprises an aqueous phase present at up to 95 wt % of the composition. The disclosed technology further relates to the use and method of improving skin firmness, or reduced skin sagging with the composition.

BACKGROUND OF THE INVENTION

Aging is a multifactorial phenomenon. The aging phenomenon may be due to one or more of genetic predisposition (known as chronological aging) and one's physiological reaction to environmental stresses (sometimes referred to as actinic aging). Actinic aging appears skin specific and is defined as the effect of the external environment on the skin’s biological response. The skin response to actinic aging, which may be caused by sun and pollution exposure, as well as smoking, is typically associated with a lack of normal hydration, apparition of telangiectasia (spider veins), sagging of the skin, and/or reduced firmness of the skin. With sagging or reduced firmness the appearance of fine lines and wrinkles occurs. The sagging or reduced skin firmness may be explained by the fact that the elastic fibers of the dermal extracellular matrix, forming the support and conferring elasticity and strength to the skin are destroyed and become rare with age.

In some instances the colour of the skin is another large contributor to a person's appearance and an uneven skin tone with visible or tactile discontinuities and puffiness are perceived as older unhealthier looking skin. The skin may have a degree of darkening or black circles. Many people are concerned with the degree of pigmentation of their skin and may wish to reduce darkening, or even lighten their 'natural' skin colour. WO2010/136965 (Fournial et al, published 2 December 2010) relates to dipeptide of formula Rl-Tyr-Arg-R2 for use as a cosmetic active compound in order to treat and/or prevent cutaneous sagging, wherein R1 and R2 are defined groups in WO2010/136965. WO2012/154949 (Florence et al., published 15 November 2012) relates to promoting the production of hyaluronic acid in skin; and promoting the synthesis of fibronectin and laminin in skin by employing a composition comprising a number of ingredients including an effective amount of tripeptide-1 to promote the production of fibronectin and laminin in skin. W02010/085532 (Ha et al., published 29 July 2010), and WO2011/017274 (Roth, published 10 February 2011) relate to compositions comprising one or more peptides for skin firming or wrinkle reduction. W02008/130752 (Faller et al., published 30 October 2008) relates to a composition comprising a peptide, and the composition can be used to treat skin to treat aged or environmentally damaged skin which can include the appearance fine lines and wrinkles, loss of elasticity, increased sagging, loss of firmness, loss of color evenness or tone, coarse surface texture, and mottled pigmentation. Reducing eye sagginess is exemplified. EP1795181 B (Potin, published 4 December 2006) relates to the use of a combination of a niacinamide and a tyrosine-arginine dipetide of a given formula to prevent or decrease red blotches and/or puffiness of skin. WO2012/125183 (Daly et al., published 20 September 2012) relates to the use of at least one extract from the Anogeissus genus for treating skin by producing fibrillin and thereby increasing skin elasticity. WO2012/143364 (Doucet et al., published 26 October 2012) relates to a cosmetic composition for use in increasing the collagen synthesis in skin comprising 0.001 - 0.5 wt% of a Phaeodactylum tricornutum extract; 0.00001 - 2.0 wt% of Dimer Tripeptide-43 or Hydrolyzed Rice Protein, the concentrations being related to the total weight of the composition; and cosmetic auxiliaries or mixtures thereof up to a total of 100 wt% of the composition. W02006/069608 (Montanari et al., published 6 July 2006) relates to a composition for skin application suitable for relaxing expression wrinkles which combines a selected active peptide component with a decontracting or relaxing action on the muscular fiber with a microelement which reduces the muscular contraction level by acting directly or indirectly on a muscular fiber component. US 5,723,482 (Degwert et al., published 3 March 1998) and W02005/049054 (Grigg, published 2 June 2005) relates to a composition comprising a carnosine (beta-alanyl-L-histidine) useful for treating damaged skin.

British Application GB 1408079.0 (Tomlinson et al., filed 7 May 2014), then PCT filed PCT/GB2014/051496 (15 May 2014) relates to a water-in-oil emulsion comprising a water phase having less than 60 wt % water, and the water phase comprises a dipeptide.

British Application GB 1408080.8 (Tomlinson et al., filed 7 May 2014), then PCT filed PCT/GB2014/051489 (15 May 2014) relates to a water-in-oil emulsion comprising a water phase having less than 60 wt % water, and the water phase comprises a matrix matalloproteinase inhibitor and a skin conditioning agent. WO2008/134712 (Yu et al., published 6 November 2008) relates to cosmetic method of skin care, the method comprising steps of: applying to the skin of a subject a cosmetically effective amount of a matrix metalloproteinase (MMP) inhibitor in a cosmetically suitable vehicle in order to improve the appearance of skin, wherein the MMP inhibitor based upon cyclic compounds having a cyclic group based upon formulae and the formulae comprise a pyran, a lactam, or a piperidine constituent. The cosmetic may be useful to prevent or reduce the appearance of the following cosmetic attributes: coarse wrinkles, fine wrinkles, lines, sagging, pigmentation changes, mottled hyperpigmentation, lentigines, tactile roughness, telangiectasia, pore size, elastosis, laxity, and redness. A number of references are known to disclose matrix metalloprotease (MMP) inhibiting agents. US2006/0074108 (Gupta, published 6 April 2006) relates to compounds that are selective inhibitors of Matrix Metalloprotease to cosmetic and pharmaceutical compositions, and the MMP compounds comprise one hydroxyaryl or polyhydroxyaryl compound. US2012/0058140 (Ceccoli et al., published 8 March 2012) relates to composition comprising: a matrix metalloprotease inhibitor component; a tissue inhibitor of matrix metalloproteases inducing agent; and an antioxidant comprising at least one natural extract. US2007/0042064 (Leverett et al., published 22 February 2007) relates to a composition comprising extracts of Durio zibethinus. The composition also allows for a method of inhibiting the induction of matrix metalloproteinase-9, and for lightening or evening skin tone. WO2012/145748 (Florence et al., published 26 October 2012) relates to a composition that includes a first MMP-1 inhibitor, wherein said first inhibitor is an extract from

Burretiodendron hsienmu, a second MMP-1 inhibitor, wherein said second inhibitor is an extract from Bauhinia brachycarpa var. cavaleriei, and a third MMP-1 inhibitor, wherein said third inhibitor is an extract from Tetracentron sinense. US 8,460,721 (Rival et al., published 11 June 2013) relates to active ingredient comprising 0.1 and 5 wt % of at least one extract of Hibiscus abelmoschus and 0.1 and 5 wt % a soy extract containing at least peptides wherein the Hibiscus abelmoschus extract.

Various applications disclose a large variety of different approaches to the use of ascorbic acid, or derivatives thereof in cosmetic or skin care formulations. The applications include: US 2,400,171 (Ruskin, published 14 May 1946), US 6,146,664 (Siddiqui, published 14 November 2000), US 8,022,090 (Choi et ah, published 20 September 2011), US2007196310 (Mary Kay, published 21 February 2007), US 2014/0155633 (Lin-Chao et al, published 5 June 2014), US 7,741,496 (Wei-Chuan et al., published 22 June 2010) and US 2011/02811943 (Pei Miu et al., published 17 November 2011), US 6,110,476 (Nguyen et al., published 29 August 2000), US 2008/0253982 (Shibayama, published 16 October 2008), EP2722043 Al (Lin et al., 23 April 2014), US 6,162,419 (Perricone et al., published 19 December 2000), US 6,087,393 (Mathur, published 7 July 2000), US 8,053,469 (8 November 2011), US 5,736,567 (Cantin et ah, published 7 April 1998), US 5,140,043 (Darr et ah, published 18 August 1992), US 6,010,706 (Candau et ah, published 4 January 2000), US 6,036,963 (Weinkauf et al, published 14 March 2000), and US 2008/0287533 (Gupta, published 20 November 2008).

SUMMARY OF THE INVENTION

The disclosed technology may be used to decrease or prevent at least one of the following forming wrinkles or fine lines, skin sagging, or hyperpigmentation (such as solar lentigines), or increasing skin firmness or skin laxity. In one embodiment the disclosed technology additionally provides whitening/lightening/even tone to skin.

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.

In one embodiment the disclosed technology relates to a composition comprising: an O-substituted ascorbic acid or derivative thereof; a matrix metalloproteinase inhibitor; and hibiscus and/or a peptide, wherein the composition comprises an aqueous phase present at up to 95 wt %, or up to 90 wt % of the composition.

The composition may be an emulsion or gel.

When the composition is an emulsion, the composition may be an emulsion comprising an oil phase and an aqueous phase present at up to 90 wt % of the composition.

When the composition is a gel, the composition further comprises a thickener.

In one embodiment the disclosed technology relates to a composition comprising an O-substituted ascorbic acid or derivative thereof, a matrix metalloproteinase inhibitor, and hibiscus, wherein the composition comprises an aqueous phase present at up to 95 wt %, or up to 90 wt % of the composition.

In one embodiment the disclosed technology relates to a composition comprising an O-substituted ascorbic acid or derivative thereof, a matrix metalloproteinase inhibitor, and a peptide, wherein the composition comprises an aqueous phase present at up to 95 wt %, or up to 90 wt % of the composition.

In one embodiment the disclosed technology relates to a composition comprising an O-substituted ascorbic acid or derivative thereof, a matrix metalloproteinase inhibitor, hibiscus and a peptide, wherein the composition comprises an aqueous phase present at up to 95 wt %, or up to 90 wt % of the composition.

In one embodiment the disclosed technology relates to a composition comprising: an O-substituted ascorbic acid or derivative thereof; a matrix metalloproteinase inhibitor; and hibiscus and/or a peptide, wherein the composition is an emulsion comprising an oil phase and an aqueous phase present at up to 90 wt % of the composition.

In one embodiment the disclosed technology relates to a composition comprising: an O-substituted ascorbic acid or derivative thereof; a thickener, a matrix metalloproteinase inhibitor; and hibiscus and/or a peptide, wherein the composition is a gel and the aqueous phase present at up to 95 wt % of the composition.

The composition disclosed herein in one embodiment further comprises a whitening/lightening agent.

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

In one embodiment the disclosed technology relate 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 decreasing or preventing at least one of the following forming wrinkles or fine lines, skin sagging, or hyperpigmentation (such as solar lentigines), or increasing skin firmness or skin laxity comprising supplying to skin the composition disclosed herein.

In one embodiment the disclosed technology relate to the use of the composition disclosed herein to decrease or prevent at least one of the following forming wrinkles or fine lines, skin sagging, or hyperpigmentation (such as solar lentigines), or increasing skin firmness or skin laxity 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.

Typically skin is a mammalian skin such as human skin.

DETAILED DESCRIPTION OF THE INVENTION

The disclosed technology provides a composition, methods and uses as disclosed above. Ο-Substituted Ascorbic Acid

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 may be 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, Cl-20 alkyl, C3-20 cycloalkyl, Cl-20 alkoxy, C2-20 acyl, C6-20 aryl, Cl-20 heterocyclic aromatic, Cl-20 heterocyclic nonaromatic, 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, Cl-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.

The O-substituted 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.

Hibiscus

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

In one embodiment the hibiscus may be Hibiscus Abelmoschus, typically Hibiscus Abelmoschus extract. The extract may be obtained from the Hibiscus Abelmoschus leaf, seed or root, typically the root.

The solvent for extraction and/or putting back into suspension may be any polar solvent as long as it makes it possible to obtain essentially all the active compounds in an aqueous extract in order to provide the properties desired within the context of the disclosed technology. The Hibiscus Abelmoschus extract may be an aqueous extract, typically obtained by extraction at ambient temperature (around 20° C to 30° C) or at a temperature from 35° C to 80° C. The extraction may utilise a hydroalcoholic, or typically a hydroglycolic solvent to produce an extract of Hibiscus Abelmoschus. Among the hydroglycolic extracts, an extraction solvent of the water/glycol type is typical. A water/butylene glycol mixture is often utilised. Among the non-hydroglycolic hydroalcoholic extracts, a water/methanol or water/ethanol solvent may by typical.

The proportions of the water/alcohol mixture, typically water/glycol mixture may vary but may range from 10/90 and 90/10, and for example between 50/50 and 80/15.

The Hibiscus extract may be obtained from 1 to 10% of the plant or part of the plant in the dry state relative to the weight of the total solution. The Hibiscus extract may be used in an amount from 0.1 to 10 wt %, or 1 to 5 wt % of the composition. In one embodiment the disclosed technology comprises 3 to 5 wt % of the Hibiscus extract.

The Hibiscus extract may comprise 1 to 10 wt %, or 2 to 6 wt % of plant extract, and 90 to 99 wt %, or 94 to 98 wt % of aqueous solution or in the hydroalcoholic solution.

Hibiscus Abelmoschus is described for example in US 8,460,721.

The Hibiscus Abelmoschus extract may be in a dry form, especially a freeze-dried form, or in suspension in an aqueous solution or in the hydroalcoholic solution.

The Hibiscus Abelmoschus extract may contain 5 main amino acids which are arginine, alanine, valine, leucine and isoleucine, which each represent at least 5%, or 6%, or more than 6% of the total amino acids of the extract.

Peptide

Peptides are defined as compounds comprising an uninterrupted sequence of amino acids. 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 dipeptidel7, palmitoyl dipeptide 5 diaminobutyroyl hydroxythreonine, palmitoyl dipeptide 5 diaminohydroxybutyrate, palmitoyl dipeptide 7 and mixtures thereof.

In one embodiment the composition of the disclosed technology comprises a peptide that may be a dipeptide, wherein said amino acid sequences of said dipeptide may be chosen from Tyr-Arg, Tyr-Val, Ala-Glu, Val-Trp, Asn-Phe, Asp-Phe and mixtures thereof. The dipeptide may be chosen from Trp-Val (tryptophan-valine), Ala-Glu (alanine-glutamine), Tyr-Arg peptide (tyrosine-argenine) and mixtures thereof. Typically the dipeptide may be N-Acetyl Tyr-Arg -1 cetyl ester.

The dipeptide may be incorporated into the composition of the disclosed technology at a level of from 0.1 to 50000 ppm, or from 1 to 5000 ppm, or from 10 to 500 ppm. For instance the dipeptide may be present at 0.1 to 50000 ppm, or 1 to 5000 ppm, or 10 to 500 ppm, or 100 to 200 ppm.

In one embodiment of the disclosed technology, the composition of the disclosed technology also comprises one or more additional peptides. The additional peptide may be chosen from a tripeptide, tetrapeptide, pentapeptide and mixtures thereof. By tripeptide, it is meant compound comprising an uninterrupted sequence of three amino acids. By tetrapeptide, it is meant a compound comprising an uninterrupted sequence of four amino acids. By pentapeptide it is meant a compound comprising an uninterrupted sequence of five amino acids.

Tripeotide

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. Another suitable tripeptide may be Arg-Lys-Arg. A typical tripeptide may be based on the structure Gly-His-Lys and its analogs and derivatives thereof. These are collectively known herein as a GHK-tripeptide. In one embodiment the tripeptide has this exact sequence of amino acids. Analogs of the tripeptide useful herein include those in which one or more of the three amino acids are reorganized or rearranged within the sequence, such as Gly-Lys-His; and/or where no more than two amino acids are substituted, such as, His-Ala-Om.

Amino acids substituted for Gly include an aliphatic side chain such as, beta-Ala, Ala, Val, Leu, Pro, Sarcosine (Sar) and He. Typically amino acids substituted for Gly include are Ala, Leu and He.

Typical amino acids substituted for Lys or His include those having a side chain that includes, predominantly, a charged nitrogen at a pH of 6, such as, Pro, Lys, Arg, His, Desmosine and Isodesmosine. Typically Lys may be replaced with Om, Arg, or Citrulline.

Derivatives are also considered to be encompassed by the term GHK-tripeptide in accordance with the disclosed technology, (and therefore also the more generic term tripeptides). Derivatives of GHK-tripeptide in accordance with the disclosed technology include derivatives of the substituted and rearranged tripeptides described herein. These derivatives include, inter alia, acyl-derivatives, which are tripeptides substituted with one or more straight-chain or branched-chain, long or short chain, saturated or unsaturated, substituted with a hydroxy, amino, acyl amino, sulphate or sulphide group, or unsubstituted, which may be derived from acetic acid, capric acid, lauric acid, myristic acid, octanoic acid, palmitic acid, stearic acid, behenic acid, linoleic acid, linolenic acid, lipoic acid, oleic acid, isostearic acid, elaidoic acid, 2-ethylhexaneic acid, coconut oil fatty acid, tallow fatty acid, hardened tallow fatty acid, palm kernel oil fatty acid, and lanolin fatty acid. Typical examples of the acyl group include an acetyl group, a palmitoyl group, an elaidoyl group, a myristyl group, a biotinyl group and an octanoyl group. These may be substituted or unsubstituted. When substituted, they are typically substituted with hydroxyl or sulphur comprising groups such as, SO3H, SH or S-S.

The His-based tripeptide includes at least one Histadine amino acid. The other two amino acids in the sequence may be the same or different. Thus, contemplated are His-Xaa-Xaa, His-Xaa-Xbb, His-Xbb-Xaa, Xbb-His-Xbb, Xbb-His-Xaa, Xaa-His-Xbb, Xaa-Xaa-His, Xaa-Xbb-His, Xbb-Xaa-His and Xbb-Xbb-His, where Xaa and Xbb are two different amino acids, although either may be His. In one embodiment at least one of the other amino acids may be Gly, beta-Ala, Ala, Val, Leu, Pro, Sarcosine (Sar) or lie. Typically at least one of the other amino acids is Pro, Lys, Arg, His, Desmosine and Isodesmosine. Lys may be replaced with Om, Arg, or Citrulline. Derivatives are also considered to be encompassed by the term His-based tripeptide in accordance with the disclosed technology, (and therefore also the more generic term tripeptides). These derivatives include, inter alia, acyl-derivatives, which are tripeptides substituted with one or more straight-chain or branched-chain, long or short chain, saturated or unsaturated substituted or unsubstituted acyl group(s) having from 1 to 29 carbon atoms. The acyl groups which may be used are the same as those described for the GHK-tripeptide.

The tripeptide may include N-Acyl-Gly-His-Lys, or typically N-Palmitoyl-Gly-His-Lys. Commercially available tripeptide and tripeptide derivative comprising compositions include Biopeptide-CL® from SEDERMA, Maxilip® from SEDERMA, Biobustyl® from SEDERMA. The tripetptide may include tetradecyl aminobutyroylvalylaminobutyric urea trifluoroacetate, palmitoyl tripeptide-5, palmitoyl dipeptide-5 diaminobutyroyl hydroxythreonine.

The tripeptide of the disclosed technology when present may be used in amounts from 0.10 ppm to 10,000 ppm, or 0.50 ppm to 5,000 ppm, or lppm to 1000 ppm, or from lppm to 500 ppm.

In one embodiment the composition further comprises a tripeptide and it may be present at 0.1 to 5000 ppm, or 0.5 to 500 ppm, or 1 to 200 ppm, or 1 to 20 ppm.

Tetrapeptide

The composition s 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. Analogs of the tetrapeptide rigin useful with the disclosed technology include those in which one or more of the four amino acids are reorganized or rearranged within the sequence and/or where no more than two of the amino acids are substituted such as Ala-Gln-Thr-Arg.

At least one of the amino acids within the sequence may be Pro or Arg. Typically the tetrapeptide includes both Pro and Arg although their order and position may vary. The amino acid substitutions may be from amongst any amino acid as defined herein. The rigin-based tetrapeptide may include Xaa-Xbb-Arg-Xcc, Xaa-Xbb-Xcc-Pro, or Xaa-Xbb-Pro-Arg, wherein Xaa-Xbb-Pro-Xcc, Xaa-Xbb-Xcc-Arg, Xaa, Xbb and Xcc may be the same or different and selected from the following Xaa is Gly or the amino acids that may be substituted therefore, Xbb is Gin or the amino acids that may be substituted therefore and Xcc may be Pro or Arg or the amino acids substituted therefore. The amino acids substituted for Gly include an aliphatic side chain such as, beta-Ala, Ala, Val, Leu, Pro, Sarcosine (Sar) and He. The amino acids substituted for Gin include a side chain that includes an amine group that is predominantly uncharged at neutral pH (pH 6-7) such as, Asn, Lys, Om, 5-hydroxyproline, Citrulline and Canavanine. When Arg is substituted, it may be replaced with an amino acid having a side chain that includes, predominantly, a charged nitrogen at a pH of 6, such as, Pro, Lys, His, Desmosine and Isodesmosine.

Derivatives are also considered to be encompassed by the term rigin-base tetrapeptide in accordance with the disclosed technology, (and therefore also the more generic term tetrapeptide). Derivatives include derivatives of the substituted and rearranged rigin-based tetrapeptide described herein. These derivatives include, inter alia, acyl-derivatives, which are tetrapeptide substituted with one or more straight-chain or branched-chain, long or short chain, saturated or unsaturated, substituted with a hydroxy, amino, amino acyl, sulphate or sulphide group or unsubstituted having from 1 to 29 carbon atoms. N-acyl-derivatives include those acyl groups which may be derived from acetic acid, capric acid, lauric acid, myristic acid, octanoic acid, palmitic acid, stearic acid, behenic acid, linoleic acid, linolenic acid, lipoic acid, oleic acid, isostearic acid, elaidoic acid, 2-ethylhexaneic acid, coconut oil fatty acid, tallow fatty acid, hardened tallow fatty acid, palm kernel oil fatty acid, lanolin fatty acid and the like. Typical examples of the acyl group include an acetyl group, a palmitoyl group, an elaidoyl group, a myristyl group, a biotinyl group and an octanoyl group. These may be substituted or unsubstituted. When substituted, they may be substituted with hydroxyl or sulphur comprising groups such as SO3H, SH or S-S.

The tetrapeptide may be an ALAMCAT tetrapeptide which includes at least one amino acid having an aliphatic group side chain. These amino acids include, Gly, beta-Ala, Ala, Val, Leu, Sarcosine (Sar) and He. The tetrapeptide of this type also includes at least one amino acid including at least one -NH2 comprising side chain. This amino acid may include a side chain that has an amine group that is predominantly uncharged at neutral pH (pH 6-7) such as, Gin, Asn, Lys, Om, 5-hydroxyproline, Citrulline and Canavanine. The ALAMCAT-tetrapeptide also includes at least one amino acid having at least one side chain including at least one cationic amine (predominant species is charged such as -NH3+, >NH2+ -basic amino acids which are positively charged at pH 6.0). These amino acids include, Pro, Arg, Lys, His, Desmosine and Isodesmosine. The remaining amino acid may be any amino acid, typically one comprising an alphatic group, pendant amino group or pendant cationic group. Derivatives are also considered to be encompassed by the term ALAMCAT-tetrapeptide in accordance with the disclosed technology, (and therefore also the more generic term tetrapeptide). These derivatives include, inter alia, acyl-derivatives, which are tetrapeptide substituted with one or more straight-chain or branched-chain, substituted or unsubstituted long or short chain, saturated or unsaturated acyl group(s) having from 1 to 29 carbon atoms. The acyl groups which may be used are the same as those described for the rigin-based tetrapeptide. A typical tetrapeptide may include Peptide E, arg-ser-arg-lys, N-acyl-Gly-Gln-Pro-Arg; and in one embodiment N-palmitoyl-Gly-Gln-Pro-Arg.

Commercially available sources of tetrapeptide includes RIGIN®, EYELISS®, Haloxyl, and MATRIXYL®3000, which comprise between palmitoyl-Gly-Gln-Pro-Arg, and other ingredients, such as peptides, chalcones and an excipient, commercially available from SEDERMA, France. Tego Pep 417 available from Evonik.

The tetrapeptide of the disclosed technology may be used in amounts from 0.1 ppm to 10,000 ppm or 0.5 ppm to 1000 ppm, or from 1 ppm to 500 ppm of the composition. In one embodiment the tetrapeptide may be present at 1 to 50 ppm.

In one embodiment the composition disclosed herein may comprise combination of a tripeptide and tetrapeptide. The typical ratio of tetrapeptide to tripeptide, or indeed the ratio of molecules having four amino acids to those having three amino acids may range from 100:1 to 1:100; from 50:1 to 1:50, or from 30:1 to 1:30, or from 10:1 to 1:10. Typically the ratio of tetrapeptide to tripeptide may range from between 3:1 to 1:3. These ratios are on a weight basis. In one embodiment, the amount of tripeptide used may be greater than the amount of tetrapeptide used when considered in terms of their amounts in parts per million, again based on overall weight of the composition.

The composition of the disclosed technology may comprise a tetrapeptide of the sequence Gly-Gln-Pro-Arg, its analogs and derivatives in combination with one or more tripeptide of the sequences Gly-His-Lys, its analogs and derivatives.

Pentapeptide

The compositions of the disclosed technology may optionally 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 pentapeptide may include lys-thr-thr-lys-ser, Arg-asp-lys-tyr-val (pentapeptide -1) and derivatives thereof. A commercially available pentapeptide derivative-comprising composition is Matrixyl of palmitoyl-lys-thr-thr-lys-ser and is commercially available from Sederma, France.

The pentapeptide when present in the composition disclosed herein may be present at 0.001 to 2 wt %, or 0.005 to 1.5 wt %, or 0.01 to 1 wt % of the composition.

The peptide may be chosen from a tri-, tetra-, or penta- peptide and present at 0.1 to 5000 ppm, or 0.5 to 500 ppm, or 1 to 200 ppm, or 1 to 20 ppm.

In one embodiment the composition of disclosed herein comprises a peptide mixture of: a di-peptide and a peptide chosen from a tri-, tetra-, and/or penta- peptide.

When in the form of a mixture: the dipeptide may be present at 0.1 to 50000 ppm, or 1 to 5000 ppm, or 10 to 500 ppm, or 100 to 200 ppm; and the peptide may be chosen from a tri-, and/or tetra- peptide and present at 0.1 to 5000 ppm, or 0.5 to 500 ppm, or 1 to 200 ppm, or 1 to 20 ppm.

Matrix Metalloproteinase Inhibitor ΓΜΜΡΠ

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). Among these groups, there are collagenases able to degrade fibrillar collagens (MMP-1 or interstitial collagenase, MMP-8 or neutrophil collagenase, MMP-13 or collagenase 3, MMP-18 or collagenase 4), gelatinases degrading type IV collagen or other denatured collagen form (MMP-2 or A gelatinase (72 kDa), MMP-9 or B gelatinase (92 kDa)), stromelysins (MMP-3 or stromelysin 1, MMP- 10 or stromelysin 2, MMP-11 or stromelysin 3) whose broad spectrum of activity targets proteins of the extracellular matrix such as glycoproteins (fibronectin, laminin), proteoglycanes, matrilysin (MMP-7), metalloelastase (MMP- 12) or metalloproteinases (MMP- 14, MMP- 15, MMP- 16 and MMP- 17). Metalloproteinases (MMPs) are proteases that use a metal, (mostly zinc) coordinated to 3 cystein residues and to a methionine in their active site , that degrade macromolecular components of the extracellular matrix and of basal layers at neutral pH (collagen, or elastin). This group of enzymes is inactivated by metal chelators. The principal activity regulators of MMPs are the tissue inhibitors of metalloproteinases or TIMPs such TIMP-I, TIMP-2, TIMP-3 and TIMP-4 (Woessner J. F., Faseb Journal, 1991). Furthermore, the MMPs expression is also regulated by growth factors, cytokins, oncogens products (ras, jun), or also matrix constituents.

The term "matrix metalloproteinase inhibitors " according to the present invention means all molecules able to reduce the MMPs activity regarding the gene expression (transcription and translation) or regarding the activation of the zymogen form of MMPs, or else regarding the local control of active forms. Furthermore, the metalloproteinase inhibitors according to the present invention can also be MMP-1 inhibitors of natural or synthetic origin. The terms "natural origin" or "synthetic origin" mean both a metalloproteinase inhibitor at a pure state or in solution at different concentrations, but natural origin termed inhibitors are obtained by different extraction methods from a natural element (for example lycopene from a tomato) whereas the inhibitors of synthetic origin are all obtained via chemical synthesis

In one embodiment the composition disclosed herein comprises an MMPi. Typical MMPi are chosen from retinoid, N-acetyl cysteine, glutathione, 2-furildioxime, vitamin C (other than the O-substituted ascorbic acid or derivative thereof), hydrolysed rice protein, alfalfa extract, white lupin, zizyphus jujube extract, kudzu extract, vitis vinifera extract, Oenothera biennis extract Anogeissus leiocarpus extract and mixtures thereof.

In one embodiment the MMPi are exclusively chosen from retinoid, N-acetyl cysteine, glutathione, 2-furildioxime, vitamin C (other than the O-substituted ascorbic acid or derivative thereof), hydrolysed rice protein, alfalfa extract, white lupin, zizyphus jujube extract, kudzu extract, vitis vinifera extract, Oenothera biennis extract Anogeissus leiocarpus extract and mixtures thereof.

Typically the MMPi may be hydrolysed rice protein. The hydrolysed rice protein may be derived Oryza Sativa, or Oryza Punctata.

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

Whitening Agent

In one embodiment the composition disclosed herein further comprises a whitening/lightening agent. When the composition further comprises the whitening/lightening agent it may be present at 0.001 to 10 wt %, or 0.01 to 5 wt %, or 0.1 to 2 wt %, or 0.2 to 1 wt % of the composition. For example the whitening/lightening agent may be present at 0.001 to 3 wt %, or 0.01 to 2 wt %, or 0.05 to 1 wt %, or 0.1 to 0.5 wt % of the composition.

The whitening/lightening may include at least one of the following ingredients: emblica, Mulberry leaf extract, mangostin, Sophora, a flavonoid, hydroxyphenoxy propionic acid (i.e., Radianskin®) and a chromane such as dimethylmethoxy chromanol.

In one embodiment the whitening/lightening agent may be a mixture of ingredients chosen from: emblica, and an antioxidant chosen from Mulberry leaf extract, mangostin, Sophora, a flavonoid, hydroxyphenoxy propionic acid and a chromane.

In one embodiment the whitening/lightening agent may be a mixture of ingredients chosen from: emblica and Sophora, optionally in the presence of Mulberry leaf extract. Typically the Mulberry leaf extract may be present.

The emblica may be emblica officinalis, typically comprises: over 40% by weight of emblica (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 Sophora Angustifolia root Extract, a Sophora flavescens root extract, a Sophora Alopecuroides Extract, or a 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 may be derived from Sophora Angustifolia root Extract or a Sophora flavescens root extract.

Typically the emblica may be Phyllanthus emblica; and Sophora may be derived from Sophora Angustifolia root Extract or a Sophora flavescens 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 anthrocyanidins 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. morns 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), French saffron, 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, grape, sage, sunflower, maritime pine bark, rosemary, marjoram, crocus, french saffron, wild carrot, hop, coffee, green coffee, witch hazel, oak, camellia, red clover, flax, ginger, magnolia, edelweiss, burdock and mixtures thereof.

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).

Skin Conditioning Agent

The composition of the present invention may optionally comprise a skin conditioning agent. The skin conditioning agents may be chosen from humectants, emollients, moisturisers, or mixtures thereof. Where present, the skin conditioning agent may be present from 0.01 to 20 wt %, or 0.1 to 10 wt %, or 0.5 to 7 wt % 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 may be 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 0.0001 to 25 wt %, or 0.001 to 15 wt %, or 0.01 to 10 wt %, or 0.1 to 5 wt %, and or 0.01 to 2 wt% of the composition, of salicylic acid. In one embodiment the salicylic acid compound may be 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'- (2ethylhexanoyl)-glycerin, c) benzophenones (for example oxybenzone), d) dibenzoylmethanes such as 4- (tert-butyl)-4'-methoxydibenzoylmethane, e) 2-phenylbenzimidazole-5 sulphonic 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 wt %, or 0.1 to 10 wt % of the composition. Other Optional Ingredients

The compositions of the present invention may also optionally comprise one or more of the following 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, phenoxyethanol, 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 wt % of the composition.

Sequestering agents may be added to the composition, such as ethyl enediamine tetraacetic acid and salts thereof, typically in an amount of from 0.005 to 0.5 wt % of the composition.

The composition may also include waxes such as cocoa butter suitably in an amount of from 0.1 tolO wt % 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 0.01 to 10 wt % of the composition.

Perfumes may be added suitably in an amount of from 0.01 to 2 wt % of the composition, as may water soluble dyes such as tartrazine, suitably in an amount of from a trace amount such as lxlO'5 to 0.1 wt % 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 0.01 to 10 wt % 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 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 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.

Gel

When in the form of a gel, the composition disclosed herein may contain 0.1 to 10 wt %, or 0.5 to 5 wt %, or 0.5 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 acryloy! methyl taurate-viny 1 pyrrolidone copolymers, or hydroxyethylaerylate/sodium acryloyldimethyl taurate copolymers, or modified celluloses e. g. hydroxyethylcellulose 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"Pluronic"®), 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 l-octenylsuccimc 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 to 95 wt % water and 0.1 to 10 wt % of a thickener, or 60 to 95 wt % water, and 0.5 to 5 wt % of a thickener, or 70 to 90 wt % of water; and 0.5 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 an oil-in-water, or water-in-silicone composition, often oil-in-water.

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, or 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, or 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.

An oil-in-water or water-in-oil emulsion may comprise an organic oil. The organic oil may be volatile or non-voaltile. The organic oil. may include a diluent, a solvent, a polyolefin polymer, or an ester oil.

The term "ester oil" means an oil that is liquid at room temperature (25 °C.) comprising at least one ester functional group. 1'he ester oil used herein is chosen, for example, from monoesters.

The ester oil may, for example, be chosen from the monoesters of formula R’COORf wherein Rl 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 R' 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 isodecyl neopentanoate; isocetyl octanoate; isononyl isononanoate, isodecyl isononanoate, tridecyl isononanoate; hexyl laurate, 2-hexyidecyl laurate; isopropyl myristate, isocetyl myristate, isotridecy! myri state, 2-octyidodecyl myri state; isopropyl palmitate, 2-ethylhexyl palmitate, isooctyl palmitate, isocetyl palmitate, isodecyl palmitate, isosteary! palmitate, 2-octyldecyl palmitate; isopropyl isostearate, 2-octyldodecyl stearate, isostearyl isostearate, and 2-octyldodecyl erucate.

The ester oil may he 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 (CEIL is a commercially available oil-in-water emulsion composition containing ascorbyl glucoside.

Example 1 (EX1): is an oil-in-water emulsion composition containing approximately 65 wt % water, 10 wt % dimethicone, 0.2 wt % hibiscus extract, 0.09 wt % hydrolysed rice protein, 0.5 wt % of 3-ethyl ascorbic acid, and 0.004 wt % a mixture of peptides.

Example 2 (ΈΧ21: is a water-in-silicone emulsion composition comprising approximately 38 wt % water, 43.2 wt % dimethicone, 0.14 wt % hibiscus extract, 0.09 wt % hydrolysed rice protein, 0.5 wt % of 3-ethyl ascorbic acid, and 0.001 wt % a mixture of peptides.

Example 3 (ΈΧ31: is a water-in-silicone emulsion composition comprising approximately 38 wt % water, 43.6 wt % dimethicone, 0.001 wt % SynTC (peptide (commercially available DSM), 0.09 wt % hydrolysed rice protein, 0.5 wt % of 3-ethyl ascorbic acid, and 0.002 wt % a mixture of other peptides.

Example 4 (EX4): is similar to EX1, except the composition comprises 0.1 wt % hibiscus extract, 0.2 wt % hydrolysed rice protein, 1 wt % of 3-ethyl ascorbic acid, and 0.05 wt % a mixture of peptides.

Example 5 (ΈΧ5): is similar to EX2, except the composition comprises 0.1 wt % hibiscus extract, 0.15 wt % hydrolysed rice protein, 0.75 wt % of 3-ethyl ascorbic acid, and 0.01 wt % a mixture of peptides.

Example 6 (EX6): is similar to EX3, except the composition comprises 0.035 wt % 0.004 wt % Syn®TC (commercially available from DSM), 0.02 wt % hydrolysed rice protein, 0.75 wt % of 3-ethyl ascorbic acid, and 0.0006 wt % a mixture of other peptides.

Each example is prepared by blending and mixing oil phase ingredients, and aqueous phase ingredients separately at a temperature of about 70 °C to ensure that all ingredients are solubilised in either water or oil. Once solubilised the oil phase and aqueous phase are blended at a temperature of about 70 °C until a homogenous emulsion composition is formed. Each example is then allowed to cool to ambient temperature.

Testing

Each example is evaluated by in an 8 week in vivo split face double blinded randomised controlled design on women aged 45 - 60 years old presenting with mild to advanced signs of ageing. Each example is applied twice a day over the designated randomised half face. Anti-ageing efficacy is evaluated by the clinical grading of numerous facial features including crows-feet wrinkles, firmness, evenness of skin tone, photodamage, peri-oral wrinkles and forehead wrinkles. Modified Griffiths’ 10 point scales are used for each skin feature assessed where: 0 = none (best possible skin condition), 1 to 3 = mild, 4 to 6 = moderate, and 7 to 9 = severe (worst possible condition). Half point scores were assigned as necessary to accurately describe the skin feature. Typically better results are obtained for examples having a higher percentage grade change increase. The percentage grade changes have been normalised for changes in untreated skin. The firmness results obtained for CE1 and EX1-EX3 are reported as follows:

The firmness results obtained indicate that the composition of the disclosed technology has improved firmness over the comparative example.

The results obtained for facial features including crows-feet wrinkles, evenness of skin tone, photodamage, peri-oral wrinkles and forehead wrinkles for CE1 and EX1 are reported below. Typically better examples are obtained for examples with higher percentage changes. The results obtained for CE1 and EX1 are:

The results obtained indicate that the composition of the disclosed technology has at least one of reduced crows feet wrinkles, reduced peri-oral wrinkles, reduced forehead wrinkles, reduced level of uneven skin tine, increased skin firmness, and reduced photo-damage to skin over the comparative example.

Claims (34)

1. CLAIMS We claim:

   1. A composition comprising: an O-substituted ascorbic acid or derivative thereof; a matrix metalloproteinase inhibitor; and hibiscus and/or a peptide, wherein the composition comprises an aqueous phase present at up to 95 wt %, or up to 90 wt % of the composition.
2. 2. The composition of claim 1 comprising an O-substituted ascorbic acid or derivative thereof; a matrix metalloproteinase inhibitor; and hibiscus, wherein the composition comprises an aqueous phase present at up to 95 wt %, or up to 90 wt % of the composition.
3. 3. The composition of claim 1 comprising an O-substituted ascorbic acid or derivative thereof; a matrix metalloproteinase inhibitor; and a peptide, wherein the composition comprises an aqueous phase present at up to 95 wt %, or up to 90 wt % of the composition.
4. 4. The composition of claim 1 comprising an O-substituted ascorbic acid or derivative thereof, a matrix metalloproteinase inhibitor, hibiscus and a peptide, wherein the composition comprises an aqueous phase present at up to 95 wt %, or up to 90 wt % of the composition.
5. 5. The composition any of preceding claim, wherein the composition is an emulsion and is an oil-in-water composition comprising 30 to 85 wt % of an aqueous phase, and 15 to 70 wt % of an oil phase.
6. 6. The composition any of preceding claim, wherein the composition is an emulsion and is an oil-in-water composition comprising 60 to 75 wt % of an aqueous phase, and 25 to 40 wt % of an oil phase.
7. 7. The composition any of preceding claim, wherein the composition further comprises a thickener.
8. 8. The composition of claim 7, wherein the composition comprises either: 50 to 95 wt % water and 0.1 to 10 wt % of a thickener, or 60 to 95 wt % water, and 0.5 to 5 wt % of a thickener, or 70 to 90 wt % of water; and 0.5 to 3 wt % of a thickener.
9. 9. The composition of any preceding claim, wherein the emulsion is a water-in-silicone oil emulsion.
10. 10. The composition of claim 9, wherein the silicone oil is a silicone elastomer.
11. 11. The composition of any preceding claim, wherein the composition is in the form of a cream, lotion or serum.
12. 12. The composition of any preceding claim, wherein the O-substituted ascorbic acid is represented by the formula:

    wherein R1 and R2 groups are independently H, Cl-20 alkyl, C3-20 cycloalkyl, Cl-20 alkoxy, C2-20 acyl, C6-20 aryl, Cl-20 heterocyclic aromatic, Cl-20 heterocyclic non-aromatic, or C3-20 cycloalkenyl.
13. 13. The composition of any preceding claim, wherein the O-substituted ascorbic acid is 3--alkyl ascorbic acid.
14. 14. The composition of any preceding claim, wherein the O-substituted ascorbic acid is 3-ethyl ascorbic acid.
15. 15. The composition of any preceding claim, wherein the matrix metalloproteinase inhibitor is present at a level of from 0.01 to 5 wt %, or 0.05 to 3 wt % or 0.25 to 2 wt %, or 0.25 to 1 wt % of the composition.
16. 16. The composition of any preceding claim, wherein the matrix metalloproteinase inhibitor is chosen from N-acetyl cysteine, glutathione, 2-furildioxime, vitamin C (other than the O-substituted ascorbic acid or derivative thereof), hydrolysed rice protein, alfalfa extract, white lupin, zizyphus jujube extract, kudzu extract, vitis vinifera extract, Oenothera biennis extract Anogeissus leiocarpus extract and mixtures thereof.
17. 17. The composition of any preceding claim, wherein the matrix metalloproteinase inhibitor is hydrolysed rice protein.
18. 18. The composition of any preceding claim, wherein the matrix metalloproteinase inhibitor is present at a level of from 0.01 to 10 wt%, or 0.1 to 5wt %, or 0.25 to 2.5 wt %, or 0.5 to 1 wt % of the composition.
19. 19. The composition of any preceding claim, wherein the peptide is a di-, tri-, tetra-, or penta- peptide.
20. 20. The composition of any preceding claim, wherein the peptide is a di- peptide.
21. 21. The composition of claim 20, wherein the di-peptide is 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 dipeptidel7, palmitoyl dipeptide 5 diaminobutyroyl hydroxy threonine, palmitoyl dipeptide 5 diaminohydroxybutyrate, palmitoyl dipeptide 7 and mixtures thereof.
22. 22. The composition of claim 20, wherein the di-peptide is chosen from Tyr-Arg, Tyr-Val, Ala-Glu, Val-Trp, Asn-Phe, Asp-Phe and mixtures thereof.
23. 23. The composition of claim 20, wherein the di-peptide is N-Acetyl Tyr-Arg -1 cetyl ester.
24. 24. The composition of any preceding claim 20 to 23, wherein the di-peptide is present at 0.1 to 50000 ppm, or 1 to 5000 ppm, or 10 to 500 ppm, or 100 to 200 ppm.
25. 25. The composition of any preceding claim 1 to 19, wherein the peptide is chosen a tri-, tetra-, or penta- peptide.
26. 26. The composition of any preceding claim 1 to 19, wherein the peptide is a tri-, or tetra-peptide.
27. 27. The composition of any preceding claim 25 to 26, wherein the peptide is chosen a tri-, tetra-, or penta- peptide is present at 0.1 to 5000 ppm, or 0.5 to 500 ppm, or 1 to 200 ppm, or 1 to 20 ppm.
28. 28. The composition of any preceding claim, wherein the peptide is a mixture of a dipeptide and a peptide chosen from a tri-, and/or tetra- peptide. 29 The composition of claim 28, wherein the dipeptide is present at 0.1 to 50000 ppm, or 1 to 5000 ppm, or 10 to 500 ppm, or 100 to 200 ppm; and the peptide is chosen from a tri-, tetra-, or penta- peptide and present at 0.1 to 5000 ppm, or 0.5 to 500 ppm, or 1 to 200 ppm, or 1 to 20 ppm.
29. 30. The composition of any preceding claim further comprising a whitening agent.
30. 31. The composition of claim 30, wherein the whitening agent when present is present in the range of 0.001 to 3 wt %, or 0.01 to 2 wt %, or 0.05 to 1 wt %, or 0.1 to 0.5 wt % of the composition.
31. 32. The cosmetic use of a composition of any preceding claim 1 to 31.
32. 33. The cosmetic use claim 32, wherein the composition is a skin care composition.
33. 34. A method of decreasing or preventing at least one of the following forming wrinkle or fine lines, skin sagging, or increasing skin firmness comprising supplying to skin a composition of any preceding claim 1 to 31.
34. 35. The use of the composition of any preceding claim 1 to 31 to: decrease or prevent at least one of the following forming wrinkles or fine lines, or skin sagging, or to increase skin firmness of skin.