AU2013202356B2 - Compositions for lightening skin color - Google Patents

Abstract

COMPOSITIONS FOR LIGHTENING SKIN COLOR 5 Skin lightening additives and skin lightening compositions having at least one of a heterosubstituted, saturated or unsaturated aliphatic acid are described. The compositions are suitable for topical application and may comprise 12-hydroxystearic acid, ricinoleic acid or both.

Description

WO 2009/153169 PCT/EP2009/056886 COMPOSITIONS FOR LIGHTENING SKIN COLOR 5 FIELD OF THE INVENTION The present invention is directed to a skin lightening additive as well as compositions comprising the same. More particularly the present invention is directed to a cosmetic composition comprising a skin lightening additive whereby the skin lightening additive 10 comprises a heterosubstituted, saturated or unsaturated aliphatic acid, or a mixture thereof. The skin lightening additive, when used, results in a cosmetic composition that can provide moisturizing benefits. Moreover it has been unexpectedly discovered that such aliphatic acids have skin lightening benefits when topically applied. 15 BACKGROUND OF THE INVENTION Many consumers are concerned with the characteristics of their skin. For example consumers are concerned with the degree of pigmentation of their skin, freckles and/or age spots. Other consumers wish to reduce skin darkening caused by exposure to sunlight. To meet the needs of consumers, many attempts have been made to 20 develop products that improve skin characteristics. The products developed thus far often tend to have low efficacy, undesirable side effects or both. Furthermore such products can be expensive and are often not an alternative for lower income consumers. 25 There is an increasing interest to develop a cosmetic composition that comprises new skin lightening additives. This invention is directed to cosmetic compositions that comprise new skin lightening additives. The cosmetic compositions of the present invention preferably comprise, as a lightening additive, compounds like 12 hydroxystearic acid, ricinoleic acid or both. The cosmetic compositions of this 30 invention result in a decrease in melanin content which is at least 8% lower (preferably at least about 11% lower) when comparing MelanoDermTM cultures treated with the same to MelanoDerm cultures that have not been subjected to a composition with the newly discovered skin lightening additives of this invention.

-2 ADDITIONAL INFORMATION Efforts have been disclosed for making skin care cosmetic compositions. In US 6 875 425, skin lightening agents with 4-substituted resorcinol derivative compounds are described. Other efforts have been disclosed for making skin treatment compositions. In US 7 250 158 5 and US 7 247 294, methods for treating with skin lightening agents are described. Still other efforts have been disclosed for treating skin, In US 5 998 423, compositions with polycyclic nitrogen heterocycles are described. None of the additional information above describes skin lightening compositions that comprise, as a lightening additive, a heterosubstituted, saturated or unsaturated aliphatic 10 acid, or mixture thereof, SUMMARY OF THE INVENTION In a first aspect, the present invention is directed to a skin lightening additive, the skin lightening additive comprising a heterosubstituted, saturated or unsaturated aliphatic acid, or both, 15 In a second aspect, the present invention is directed to a cosmetic composition for skin lightening, the cosmetic composition comprising a skin lightening agent comprisingthe skin lightening additive of the first aspect of this invention. In a third aspect, the present invention is directed to a method for lightening skin with the cosmetic composition of the second aspect of this invention. 20 in a further aspect the present invention is directed to a method for lightening skin comprising the steps of: a) identifying skin where skin lightening is desired; b) contacting the skin with a composition comprising a skin lightening active comprising 12-hydroxystearic acid and/or a salt and/or an ester -2A thereof, and a cosmetic carrier; and c) lightening skin wherein 12-hydroxystearic acid and/or a salt and/or an ester thereof is or are capable of lightening skin, S the composition further comprising niacinamide, dioic acid, stearic acid, resorcinol or a mixture thereof. All other aspects of the present invention will more readily become apparent upon considering the detailed description and examples which follow. As used herein, a decrease in melanin content means a melanin content decrease when 10 comparing two (2), three week old MatTek MelanoDerm cultures that have not WO 2009/153169 PCT/EP2009/056886 -3 been treated with a composition comprising the skin lightening additive of this invention to two (2), three week old MatTek MelanoDerm cultures that have been treated with a composition comprising the skin lightening additive of this invention wherein treated means: 5 (a) placing the MelanoDerm culture within a six (6) well tissue culture dish and set about 0.3 cm off of the tissue culture dish; (b) subjecting the MelanoDerm culture to 0.1 and 5 micromolar compositions having the skin lightening additive of this invention, the composition being one 10 prepared from a 10 millimolar solution of skin lightening additive and carrier (e.g. dimethyl sulfoxide) having been diluted with Dulbecco's Modified Eagle Media; and (c) comparing the treated and untreated cultures by obtaining average melanin content (expressed in micrograms) by extracting melanin from MelanoDerm and 15 obtaining absorbance readings at 490 nm (OD490) using a commercially available spectrophotometer like a Hach spectrophotometer. Cosmetic composition, as used herein, is meant to include a composition for topical application to skin of mammals, especially humans. Such a composition may be 20 generally classified as leave-on or rinse off, and is meant to include conditioners or tonics, lipsticks, color cosmetics, and general topical compositions that in some fashion and at the very least reduces the effect of melanin on keratinocytes. Lightening and whitening as used herein are meant to mean the same and they include the lightening of skin directly as well as the lightening of spots on the skin, like age spots and 25 freckles. Dulbecco's Modified Eagle Media means the nutrient solution sold by MatTek Corporation and treated and used according to instructions supplied with the product commercially identified as MEL3001OBBLLMM. Skin lightening additive means a component suitable to result in physical, but especially biological whitening (i.e. a reduction in melanin production) whereby the skin lightening additive can comprise, 30 consist essentially of or consist of the skin lightening additive. MelanoDerm means the product having normal, human-derived epidermal keratinocytes and melanocytes which have been cultured to form a multilayered, highly differentiated model of the human epidermis, all of which is made commercially available by MatTek Corporation.

WO 2009/153169 PCT/EP2009/056886 -4 Unsaturated, as used herein, means having at least one bond that is not sp hybridized. Comprising, as used herein, is meant to include consisting essentially of and consisting of. 5 The cosmetic composition of the present invention can be in the form of a liquid, lotion, cream, serum, gel, soap bar or toner, or applied via a face mask or patch. The composition of this invention is one that at the very least, lightens skin when skin is meant to include skin on the face, neck, chest, back, arms, hands, legs and scalp. All ranges identified herein are meant to implicitly include all ranges subsumed therein, if, 10 for example, reference to the same is not explicitly made. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The only limitation with respect to the skin lightening additive that may be used in this invention is that the same may be used in a topical composition suitable for use on 15 humans. The preferred additive is a heterosubstituted, saturated or unsaturated aliphatic acid or a mixture thereof. In a most preferred embodiment, the skin lightening additive employed in the present invention comprises a compound having the formulae: 20 0 CR3-(CR 2 )n-CR 2 - C I' O0H 0 1 | II

CR

3 -( CR 2 )s-(CR )=(CR )-(CR2)e-C OH 0 0 CR3-(CR 2 ) t (CR =CR) (CR2)t-( C-CR- CR -(CR2 ) \ or a mixture thereof, 25 wherein each R is independently hydrogen, hydroxyl, C 1

_

6 alkoxy, C 1

_

6 alkyl, arylalkyl or an amine, with the proviso that at least one R group comprises a heteroatom; each R 1 WO 2009/153169 PCT/EP2009/056886 -5 is independently hydrogen, C 1

_

6 alkoxy, C 1

_

6 alkyl, arylalkyl or an amine; n is an integer from 7 to 19; and s and e are each independently an integer from 0 to 8, where s+e > 6 ; q is an integer from 6 to 11; each r is independently an integer from 0 to 1, with the proviso that each r is not 1 when x is 1; x is an integer from 0 to 1 with the proviso 5 that x is 0 when at least one r is 1; and each t is independently an integer from 1 to 7. The preferred compounds suitable for use in this invention (either alone or in a mixture) are aleuritic acid; phloionolic acid; 9, 10, 13-trihydroxy-11-octadecenoic acid; 9, 1 3-dihydroxy-12-ethoxy-10-octadecenoic acid; 9-hydroxy-10,12-octadecadienoic 10 acid; 4, 14-dihydroxy-octadecanoic acid; 12-hydroxystearic acid (12 hydroxyoctadecanoic acid); lesquerolic acid; ricinelaidic acid; ambrettolic acid, and rincinoleic acid (12-hydroxy-9-cis-octadecanoic acid) as represented by either formula I or II. Other preferred compounds suitable for use in this invention include beta dimorphecolic acid; densipolic acid; 8-methoxy-13-hydroxy-9, 1 1-octadecadienoic acid; 15 7-oxo-octadecanoic acid; 9-oxo-octadecanoic acid; 12-oxo-octadecanoic acid and 10 oxo-14-methyl-pentadecanoic acid as represented by formula Ill. Furthermore it is within the scope of the present invention to include any derivative (like an ester derivative) and/or salt of the acid represented by formulae I-Ill, and especially, Mg, Na and/or Ca salts thereof. Such compounds are commercially available from suppliers 20 like Vertellus Specialties Inc. Welch, Home & Clark Co. Inc. as well as Croda Chemicals. The cosmetic compositions of the present invention typically comprise from 0.001 to 15% by weight, and preferably from 0.1 to 12%, and most preferably from 1 to 10% by weight skin lightening additive based on total weight of the cosmetic composition 25 and including all ranges subsumed therein. While it is within the scope of this invention for the skin lightening additive to consist essentially of and to consist of heterosubstituted, saturated or unsaturated aliphatic acid or a mixture thereof, in an often desired embodiment, the skin lightening additive 30 of this invention comprises from 0.2 to 95%, and preferably from 10 to 85%, and most preferably from 30 to 65% by weight heterosubstituted saturated or unsaturated aliphatic acid or a mixture thereof based on total weight of skin lightening additive and including all ranges subsumed therein.

WO 2009/153169 PCT/EP2009/056886 -6 In yet another desired embodiment, the cosmetic composition of this invention comprises from 2 to 9%, and preferably from 3 to 8%, and most preferably from 3 to 6% by weight heterosubstituted, saturated or unsaturated aliphatic acid, or a mixture thereof based on total weight of the cosmetic composition and including all ranges 5 subsumed therein. When used in combination the weight ratio of heterosubstituted, saturated or unsaturated aliphatic acid to heterosubstituted, saturated aliphatic acid is from 5:95 to 95:5, and preferably from 20:80 to 80:20, and most preferably from 40:60 to 60:40 10 including all ratios subsumed therein. It should be known that commercially acceptable and conventional vehicles may be used acting as diluents, dispersants and/or carriers for the skin lightening agents and additives described herein and for any other optional but often preferred additives. 15 Therefore the cosmetically acceptable vehicle suitable for use in this invention may be aqueous-based, anhydrous or an emulsion whereby a water-in-oil or oil-in-water emulsion is generally preferred. If the use of water is desired, water typically makes up the balance of the cosmetic composition, and preferably makes up from 5 to 99%, and most preferably from 40 to 80% by weight of the cosmetic composition including all 20 ranges subsumed therein. In addition to water, organic solvents may be optionally included to act as carriers or to assist carriers within the compositions of the present invention. Illustrative and non-limiting examples of the types of organic solvents suitable for use in the present 25 invention include alkanols like ethyl and isopropyl alcohol, mixtures thereof or the like. Other optional additives suitable for use include ester oils like isopropyl myristate, cetyl myristate, 2-octyldodecyl myristate, avocado oil, almond oil, olive oil, neopentylglycol dicaprate, mixtures thereof or the like. Typically such ester oils assist in emulsifying 30 the cosmetic composition of this invention, and an effective amount is often used to yield a stable, and most preferably water-in-oil emulsion.

WO 2009/153169 PCT/EP2009/056886 -7 Emollients may also be used, if desired, as carriers within the cosmetic composition of the present invention. Alcohols like 1-hexadecanol (i.e. cetyl alcohol) and phenoxyethanol are often desired as are the emollients generally classified as silicone oils and synthetic esters. Silicone oils suitable for use include cyclic or linear 5 polydimethylsiloxanes containing from 3 to 9, preferably from 4 to 5, silicon atoms. Non-volatile silicone oils useful as an emollient material in the inventive cosmetic composition described herein include polyalkyl siloxanes, polyalkylaryl siloxanes and polyether siloxane copolymers. The essentially non-volatile polyalkyl siloxanes useful herein include, for example, polydimethylsiloxanes. 10 The ester emollients that may optionally be used are: (1) Alkenyl or alkyl esters of fatty acids having 10 to 20 carbon atoms. Examples thereof include isoarachidyl neopentanoate, isononyl isonanonoate, oleyl myristate, oleyl stearate and oleyl oleate. 15 (2) Ether-esters such as fatty acid esters of ethoxylated fatty alcohols. (3) Polyhydric alcohol esters. Ethylene glycol mono- and di-fatty acid esters, diethylene glycol mono-and di-fatty acid esters, polyethylene glycol (200-6000) mono- and di-fatty acid esters, propylene glycol mono- and di-fatty acid esters, polypropylene glycol 2000 monooleate, polypropylene glycol 2000 monostearate, 20 ethoxylated propylene glycol monostearate, glyceryl mono- and di-fatty acid esters, polyglycerol poly-fatty esters, ethoxylated glyceryl mono-stearate, 1,3 butylene glycol monostearate, 1,3-butylene glycol distearate, polyoxyethylene polyol fatty acid ester, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters are satisfactory polyhydric alcohol esters. 25 (4) Wax esters such as beeswax, spermaceti, stearyl stearate and arachidyl behenate. (5) Sterols esters, of which cholesterol fatty acid esters are examples. Emollients when used, typically make up from 0.1 to 50% by weight of the cosmetic composition including all ranges subsumed therein. 30 Fatty acids having from 10 to 30 carbon atoms may also be included as cosmetically acceptable carriers within the composition of the present invention. Illustrative examples of such fatty acids include pelargonic, lauric, myristic, palmitic, stearic, WO 2009/153169 PCT/EP2009/056886 -8 isostearic, oleic, linoleic, arachidic, behenic or erucic acid and mixtures thereof. Compounds that are believed to enhance skin penetration, like dimethyl sulfoxide, may also be used as an optional carrier. 5 Humectants of the polyhydric alcohol type may also be employed in the cosmetic compositions of this invention. The humectant often aids in increasing the effectiveness of the emollient, reduces scaling, stimulates removal of built-up scale and improves skin feel. Typical polyhydric alcohols include glycerol, polyalkylene glycols and more preferably alkylene polyols and their derivatives, including propylene glycol, 10 dipropylene glycol, polypropylene glycol, polyethylene glycol and derivatives thereof, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol, 1,2,6-hexanetriol, ethoxylated glycerol, propoxylated glycerol and mixtures thereof. For best results the humectant is preferably propylene glycol or sodium hyaluronate. The amount of humectant may range anywhere from 0.2 to 25%, and preferably from 0.5 to 15% by 15 weight of the cosmetic composition based on total weight of the cosmetic composition and including all ranges subsumed therein. Thickeners may also be utilized as part of the cosmetically acceptable carrier in the cosmetic compositions of the present invention. Typical thickeners include cross-linked 20 acrylates (e.g. Carbopol 982), hydrophobically-modified acrylates (e.g. Carbopol 1382), cellulosic derivatives and natural gums. Among useful cellulosic derivatives are sodium carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, ethyl cellulose and hydroxymethyl cellulose. Natural gums suitable for the present invention include guar, xanthan, sclerotium, carrageenan, 25 pectin and combinations of these gums. Amounts of the thickener may range from 0.0 to 5%, usually from 0.001 to 1%, optimally from 0.01 to 0.5% by weight. Collectively, the water, solvents, silicones, esters, fatty acids, humectants and/or thickeners will constitute the cosmetically acceptable carrier in amounts from 1 to 30 99.9%, preferably from 80 to 99% by weight. Surfactants may also be present in cosmetic compositions of the present invention. Total concentration of the surfactant will range from 0 to 40%, and preferably from 0 to 20%, WO 2009/153169 PCT/EP2009/056886 -9 optimally from 0 to 5% by weight of the composition. The surfactant may be selected from the group consisting of anionic, nonionic, cationic and amphoteric actives. Particularly preferred nonionic surfactants are those with a C 10

-C

20 fatty alcohol or acid hydrophobe condensed with from 2 to 100 moles of ethylene oxide or propylene oxide 5 per mole of hydrophobe; C 2

-C

10 alkyl phenols condensed with from 2 to 20 moles of alkylene oxide; mono- and di- fatty acid esters of ethylene glycol; fatty acid monoglyceride; sorbitan, mono- and di- C 8

-C

20 fatty acids; block copolymers (ethylene oxide/propylene oxide); and polyoxyethylene sorbitan as well as combinations thereof. Alkyl polyglycosides and saccharide fatty amides (e.g. methyl gluconamides) are also 10 suitable nonionic surfactants. Preferred anionic surfactants include soap, alkyl ether sulfate and sulfonates, alkyl sulfates and sulfonates, alkylbenzene sulfonates, alkyl and dialkyl sulfosuccinates, C 8

-C

20 acyl isothionates, acyl glutamates, C 8

-C

2 0 alkyl ether phosphates and combinations thereof. 15 Perfumes may be used in the cosmetic composition of this invention. Illustrative non limiting examples of the types of perfumes that may be used include those comprising terpenes and terpene derivatives like those described in Bauer, K., et al., Common Fragrance and Flavor Materials, VCH Publishers (1990). 20 Illustrative yet non-limiting examples of the types of fragrances that may be used in this invention include myrcene, dihydromyrenol, citral, tagetone, cis-geranic acid, citronellic acid, or cis-geranic acid nitrile, mixtures thereof or the like. 25 Preferably, the amount of fragrance employed in the cosmetic composition of this invention is in the range from 0.0% to 10%, more preferably 0.00001% to 5 wt %, most preferably 0.0001% to 2%. Various types of optional additional active ingredients may be used in the cosmetic 30 compositions of the present invention. Actives are defined as skin benefit agents other than emollients and other than ingredients that merely improve the physical characteristics of the composition. Although not limited to this category, general WO 2009/153169 PCT/EP2009/056886 - 10 examples include talcs and silicas, as well as alpha-hydroxy acids, beta-hydroxy acids, peroxides, zinc salts and sunscreens. Beta-hydroxy acids include salicylic acid, for example. Zinc pyrithione is an example of 5 the zinc salts useful in the cosmetic composition of the present invention. Sunscreens include those materials commonly employed to block ultraviolet light. Illustrative compounds are the derivatives of PABA, cinnamate and salicylate. For example avobenzophenone (Parsol 1789®), octyl methoxycinnamate and 2-hydroxy-4 10 methoxyl benzophenone (also known as oxybenzone) can be used. Octyl methoxyci n na mate and 2-hydroxy-4-methoxy benzophenone are commercially available under the trademarks Parsol MCX and Benzophenone-e respectively. The exact amount of sunscreen employed in the compositions can vary depending upon the degree of protection desired from the sun's UV radiation. Additives that reflect or 15 scatter the suns rays may also be employed. These additives include oxides like zinc oxide and titanium dioxide. Many cosmetic compositions, especially those containing water, should be protected against the growth of potentially harmful microorganisms. Anti-microbial 20 compounds, such as triclosan, and preservatives are typically necessary. Suitable preservatives include alkyl esters of p-hydroxybenzoic acid, hydantoin derivatives, propionate salts and a variety of quaternary ammonium compounds. Particularly preferred preservatives of this invention are methyl paraben, propyl paraben, phenoxyethanol and benzyl alcohol. Preservatives will usually be employed in 25 amounts ranging from 0.1% to 2% by weight of the composition. Still other optional ingredients that may be used with the cosmetic composition of this invention include dioic acids (e.g. malonic acid and sebacic acid), antioxidants like vitamin E, vitamins like niacinamide and vitamin C and its derivatives, recorcinols and 30 its derivatives (including those esterified with, for example, ferulic acid, vanillic acid or the like) and retinoids, including retinoic acid, retinal, retinol and retinyl esters, conjugated linoleic acid, petroselinic acid and mixtures thereof, as well as any other WO 2009/153169 PCT/EP2009/056886 - 11 conventional ingredients well known for wrinkle-reducing, skin whitening, anti-acne effects and reducing the impact of sebum. The cosmetic compositions of the present invention are intended for use primarily as a 5 product for topical application to human skin, especially and at least as a product for lightening the skin. Thus the inventor has discovered that the described aliphatic acids have excellent skin lightening capabilities whereby the same may be employed as skin lightening additives in topical cosmetic compositions that are applied topically to areas of the skin where lightening or whitening is desired. Other benefits may include skin 10 moisturizing, decreasing the effect of sebum on the skin and skin wrinkle reducing. Often the cosmetic composition of the present invention has a melting point from 30'C to 45'C, including all ranges subsumed therein. In an especially preferred embodiment, the cosmetic composition of the present invention has a pH from 4.5 to 7.5 including all ranges subsumed therein. 15 When making the cosmetic composition of the present invention, the desired ingredients are mixed in no particular order and usually at temperatures from 70 to 80'C and under atmospheric pressure. 20 The packaging for the composition of this invention can be a patch, bottle, tube, roll ball applicator, propellant driven aerosol device, squeeze container or lidded jar. The examples which follow are provided to illustrate and facilitate an understanding of the invention. The examples are not intended to limit the scope of the claims. 25 Examples Commercially available human skin equivalents (MelanoDerm TM from MatTek) were obtained for testing the impact of heterosubstituted, saturated or unsaturated aliphatic acid on melanogenesis. Solutions having a final concentration of 0.1 to 5 30 micromolar were prepared from a 10 millimolar dimethyl sulfoxide stock solution and dosed ten (10) times in a three (3) week period into the media of the MelanoDerm cultures. The media consisted of commercially available basal Dulbecco's Modified Eagles media prepared and treated in the manner set forth in the manufacturer's WO 2009/153169 PCT/EP2009/056886 - 12 instructions. For long term maintenance of the MelanoDerms, the basal media was supplemented with basic fibroblast growth factor (bFGF) and alpha melanocyte stimulating hormone (MSH) to stimulate melanocyte growth and melanogenesis. Each treatment condition was done in duplicate and three (3) sets were made for each 5 treatment as well as for a control (culture not treated with the aliphatic acid). The cultures were maintained at a temperature of 37 0 C and incubated in a humidified, 5%

CO

2 incubator during the dosing period, but removed while being dosed. After a three (3) week period, the MelanoDerm cultures were removed and solubilized 10 in a centrifuge tube containing 250 microliters of Solvable reagent (GNE9100, Packard) for sixteen (16) hours (overnight) in a 60'C oven. Following solubilization, the centrifuge tube containing the sample was spun at 12,000 g for five (5) minutes. Two hundred (200) microliters of supernatant were removed and placed in a ninety-six (96) well plate. A spectrophotometer was used to measure the absorbance of the 15 supernatant at 490 nm. A standard curve using synthetic melanin was set up in parallel to allow quantitation of melanin, in micrograms, of the samples. The results are provided below: Tables 20 Active MC* Value Range Average MC AMC Control 76.0-78.4 77.2 -- Aliphatic acid' 67.9 - 69.2 68.6 8.6 25 Active MC Value Range Average MC AMC Control 76.0-78.4 77.2 -- 30 Aliphatic acid" 69.9 - 67.6 68.8 8.4 i= ricinoleic acid (0.1uM) 35 ii = 12-hydroxystearic acid (5uM) * MC = melanin content - 13 The results, as they relate to MelanoDerm cultures, show that cosmetic compositions with the aliphatic acids of this invention unexpectedly result in skin lightening. Throughout this specification and the claims which follow, unless the context requires 5 otherwise, the word "comprise", and variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. The reference in this specification to any prior publication (or information derived from it), 10 or to any matter which is known, is not, and should not be taken as, an acknowledgement or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

Claims (25)

1. A method for lightening skin comprising the steps of: a) identifying skin where skin lightening is desired; b) contacting the skin with a composition comprising a skin lightening active 5 comprising 12-hydroxystearic acid and/or a salt and/or an ester thereof, and a cosmetic carrier; and c) lightening skin wherein 12-hydroxystearic acid and/or a salt and/or an ester thereof is or are capable of lightening skin, 10 the composition further comprising niacinamide, dioic acid, stearic acid, resorcinol or a mixture thereof.

2. The method according to claim 1 wherein the dioic acid is malonic acid or sebacic acid. 15

3. The method according to claim 1 or claim 2 wherein the composition further comprises an alpha-hydroxy acid, beta-hydroxy acid, sunscreen or a mixture thereof. 20

4. The method according to any one of the preceding claims wherein the composition further comprises conjugated linoleic acid, petroselinic acid or both.

5. The method according to any one of the preceding claims wherein the composition further comprises antioxidant. 25

6. The method according to any one of the preceding claims wherein the composition further comprises an additional additive selected from aleuritic acid, phloionolic acid, 9,10,13-trihydroxy-11-octadecanoic acid, 9,13-dihydroxy-12-ethoxy-10 octadecanoic acid, 9-hydroxy-10, 12-Octadecanoic acid, 4,14-dihydroxy 30 octadecanoic acid, lesquerolic acid; ricinelaidic acid; ambrettolic acid; ricinoleic acid; beta-dimorphecolic acid; densipolic acid; 8-methoxy-13-hydroxy-9, 11- H:\IgI\Intrwovn\NRPortbI\DCC\LGL\669059I .doc-3/09/2014 - 15 octadecanoic acid; 7-oxo-octadecanoic acid; 9-oxo-octadecanoic acid; 12-oxo octadecanoic acid; 10-oxo-14-methyl-pentadecanoic acid or a mixture thereof.

7. The method according to any one of the preceding claims wherein the composition 5 further comprises 12-oxo-octadecanoic acid.

8. The method according to claim 6 wherein the weight ratio of 12-hydroxystearic acid and/or a salt and/or ester thereof and the additional additive is from about 5:95 to about 95:5. 10

9. The method according to claim 7 wherein 12-hydroxystearic acid and/or a salt and/or an ester thereof and 12-oxo-octadecanoic acid is present at a weight ratio from about 5:95 to about 95:5. 15

10. The method according to any one of the preceding claims wherein the composition comprises from about 2 to about 9 percent by weight 12-hydroxystearic acid and/or a salt and/or an ester thereof.

11. The method according to any one of the preceding claims wherein the skin 20 lightening active makes up from about 0.001 to about 15% by weight of the composition.

12. The method according to any one of the preceding claims wherein the skin lightening active consists essentially of 12-hydroxystearic acid and/or a salt thereof 25 and/or an ester thereof.

13. The method according to any one of the preceding claims wherein the skin lightening active consists of 12-hydroxystearic acid and/or a salt and/or an ester thereof. 30 H:\IgI\Intrwovn\NRPortbI\DCC\LGL\669059I .doc-3/09/2014 -16

14. The method according to any one of the preceding claims wherein the skin lightening active consists of 12-hydroxystearic acid and/or a salt thereof.

15. The method according to any one of the preceding claims wherein skin lightening 5 active makes up from about 0.1 to about 12% by weight of the composition.

16. The method according to any one of the preceding claims wherein skin lightening active makes up from about 0.1 to about 10% by weight of the composition. 10

17. The method according to any one of the preceding claims wherein the composition is in the form of a leave-on lotion, liquid, cream, serum, gel or toner, or is applied with a patch or face mask.

18. The method according to any one of the preceding claims wherein the composition 15 is applied directly to spots on skin to lighten the spots.

19. The method according to any one of the preceding claims wherein the composition is applied directly to skin to suppress melanin production.

20 20. The method according to any one of the preceding claims wherein the skin is skin on the face or hands.

21. The method according to any one of the preceding claims wherein the composition further comprises resorcinol. 25

22. The method according to claim 17 wherein the composition is in the form of a leave-on lotion, liquid, cream, serum, gel or toner, or is applied with a patch or face mask. 30

23. The method according to any one of the preceding claims wherein the composition is a leave-on lotion, cream or serum. H:\IgI\Intrwovn\NRPortbI\DCC\LGL\669059I .doc-3/09/2014 - 17

24. The method according to any one of the preceding claims wherein the composition further comprises sunscreen and has a pH from about 4.5 to about 7.5. 5

25. A method according to claim 1 substantially as hereinbefore described with reference to the examples.