WO2001013882A1 - Methods of lightening keratinous tissue by topical application of oxime compound containing compositions - Google Patents

Abstract

The present invention relates to methods of lightening keratinous tissue which comprise topically applying to the keratinous tissue in need of treatment a safe and effective amount of a composition comprising a safe and effective amount of an oxime compound and a dermatologically acceptable carrier for the oxime compound. More particularly, the present invention relates to methods of lightening skin, e.g., lightening hyperpigmented regions of skin, and of lightening skin by regulating melanin in skin, in the same manner as mentioned above.

Description

METHODS OF LIGHTENING KERATINOUS TISSUE BY TOPICAL APPLICATION OF OXIME COMPOUND CONTAINING COMPOSITIONS

TECHNICAL FIELD The subject invention relates to the field of lightening keratinous tissue, particularly rnarnmalian keratinous tissue, by application of compositions to the keratinous tissue, e.g , skin The invention further relates to methods of lightemng keratmous tissue which mvolve the topical application of compositions containing oxime compounds. In particular, the present invention relates to methods of hghtenmg hyperpigmented regions m sk n by topical application of such compositions

BACKGROUND OF THE INVENTION

Many personal care products currently available to consumers are directed primarily to improving the health and/or physical appearance of the various types of keratmous tissue which are present m mammals, particularly humans, e g., the skin, hair, and nails Among these products, many skin care products, in particular, are directed to delaying, minimizing or even eliminating histological changes typically associated with the agmg of skin or environmental damage to skin, e.g , skin wrinkling.

Skin is subject to msults by many extrinsic and intrinsic factors Extrinsic factors include ultraviolet radiation (e g , from sun exposure), heat, wind, low humidity, harsh surfactants, abrasives, and the like. Intrinsic factors include chronological agmg and other biochemical changes from within the skin Whether extrinsic or intrinsic, these factors result in visible and/or tactile signs of skin agmg, such as wrinkling, saggmg, inelasticity, sallowness, changes in skin pigmentation and other histological changes associated with skin agmg. To many people, such changes are a reminder of the disappearance of youth As a result, treatments directed to the amelioration of such signs have become a booming busmess m youth- conscious societies. Treatments range from cosmetic creams and moisturizers to various forms of cosmetic surgery.

These extrinsic or intrinsic factors, e g., chrome exposure to UV light and chronological agmg, may result in regions of hyperpigmentation m the skin. Certain forms of non-uniform pigmentation or hyperpigmentation, e.g., age spots, freckles, pigment spots, brown spots, liver spots, melasma, cholasma, ephehdes, semle lentigenes, suntan, melanoderma, hyperpigmented macules, sun spots, melanin spots, brown patches, pigment blotchmess, mottled pigmentation, inflammatory and post-inflammatory hyperpigmentation (e.g., from acne, abrasion, ingrown hairs, insect bites, etc.), pregnancy spots, moles, and the like involving concentration of melanin m the skin, are believed to result from changes in the melanocytes and the keratmocytes present m the epidermis Melanocytes, which are located at the base of the epidermis, lose their normal regulation process with agmg and or exposure to extrinsic factors and produce excess pigment. This excess production leads to the formation of dense peπnuclear clumps of melanin m keratmocytes within the epidermis, resulting m areas of hyperpigmentation Traditional therapy for hyperpigmented skin includes the application of certain skin lightening agents, such as kojic acid, arbutin, hydroquinone or ascorbic acid, which inhibit melanin formation. A mechanism of action for these materials which has been proposed in the art is tyrosinase inhibition and/or inhibition of other steps in melanin synthesis. Tyrosinase is present within the melanosomes in epidermal melanocytes and catalyzes the committed step in the formation of melanin from tyrosine. See Goldsmith, L. A., Physiology, Biochemistry, and Molecular Biology of the Skin, Oxford University Press, pp. 873-903 (N.Y. 1991). Tyrosinase catalyzes the hydroxylation of tyrosine and the oxidation of DOPA to DOPA quinone:

tyrosinase

. tyrosine . + O v ydroxylase )

e

Binding of an inhibitor to the active site of tyrosinase results in decreased melanin formation. See generally Prota, G. Melanins and Melanogenesis, Academic Press, Inc., (San Diego 1992). The conversion of DOPA quinone to melanin occurs via non-enzymatic or spontaneous chemical reactions, some of which involve reactive oxygen or oxygen radicals.

Unfortunately, the efficacy of kojic acid and arbutin is marginal. Furthermore, hydroquinone has been associated with side effects due to cytotoxicity of the inhibitor's oxidized products. Ascorbic acid suffers from chemical stability problems and is therefore difficult to formulate into products having a shelf life needed for normal use. Similarly, consumers often experience problems with other keratmous tissues luce then hair or nails where lightemng of such tissues is desirable m certam circumstances. For example, consumers often desne to lighten facial or other body hair or nail beds. There are, however, few products that are able to lighten such tissues m a safe and effective manner which is aesthetically pleasmg to the consumer.

There is therefore a need for the development of keratmous tissue lightening methods which are more efficacious, safer, and which mvolve compositions which are easier to formulate

It has now been found that topical compositions contammg oxime compounds are useful for lightemng keratmous tissue, including nails, hair, and skin (especially hyperpigmented regions of skin).

SUMMARY OF THE INVENTION The present mvention relates to methods of lightemng keratmous tissue which comprise topically applymg to the keratmous tissue m need of such treatment a safe and effective amount of a composition comprising a safe and effective amount of an oxime compound and a dermatologically acceptable earner for the oxime compound More particularly, the present mvention relates to methods of lightemng skin, e g , lightemng hyperpigmented regions of skin, and of lightemng skin by regulating melanin m skin, m the same manner as mentioned above

DETAILED DESCRIPTION OF THE INVENTION

It has been unexpectedly found that compositions which contam certam oxime compounds are useful for achieving lightemng of keratmous tissue, mcludmg lightemng of hyperpigmented regions in mammalian skm and lightemng of hair and nail beds when applied topically to the respective keratmous tissue types. The subject mvention is not limited to any particular mechamsm of action, but is believed to operate by the inhibition of oxidative processes mvolved in the non-enzymatic steps m melanin production and/or by preventing reactive oxygen/oxygen radical stimulation (oxidative stress) of melanocytes which results m initiation of the melanin production pathway within the melanocytes, e g , which can occur with UV or sunlight exposure or other intrinsic or extrinsic stress, such as that mduced by mflammation, on the melanocyte.

All percentages and ratios used herein are by weight of the total composition and all measurements made are at 25°C, unless otherwise specified.

The compositions of the present mvention can comprise, consist essentially of, or consist of, the essential as well as optional ingredients and components described herem As used herein, "consisting essentially of means that the composition or component may mclude additional ingredients, but only if the additional ingredients do not materially alter the basic and novel characteristics of the claimed compositions or methods.

All publications cited herem are hereby incorporated by reference m then entirety.

As used herem, "keratmous tissue" refers to keratin-containing layers disposed as the outermost protective covering of mammals which mcludes, but is not limited to, skin, hair, and nails (e.g., toenails, fingernails, hooves, cuticles, etc.). The term "topical application", as used herem, means to apply or spread the compositions of the present mvention onto the surface of the keratmous tissue Preferred compositions of the present mvention are those m a form mtended to be left m contact with the keratmous tissue for an extended peπod (e.g., for several hours) after topical application, e.g., typical usage of a cream, lotion, moisturizer or the like.

The term "dermatologically-acceptable," as used herem, means that the compositions or components thereof so described are suitable for use m contact with mammalian keratmous tissue, e.g , that of humans, without undue toxicity, incompatibility, instability, allergic response, and the like.

The term "safe and effective amount" as used herem means an amount of a compound or composition sufficient to significantly mduce the mtended benefit, but low enough to avoid seπous side effects, i.e., to provide a reasonable benefit to risk ratio, within the scope of sound judgment of the skilled artisan

The methods of the present mvention are useful for lightemng keratmous tissue, e g , skin which is hyperpigmented As used herem, "hyperpigmentation" means refers to concentrations of melanin m the skm which result m age spots, freckles, pigment spots, brown spots, liver spots, melasma, cholasma, ephehdes, semle lentigenes, suntan, melanoderma, hyperpigmented macules, sun spots, melanin spots, brown patches, pigment blotchiness, mottled pigmentation, inflammatory and post-inflammatory hyperpigmentation (e g , from acne, abrasion, ingrown hairs, insect bites, etc ), pregnancy spots, moles, and the like which are believed to result from changes m the melanocytes and the keratmocytes present m the epidermis.

The compositions of the present mvention are especially useful for regulating keratmous tissue pigmentation associated with melanin. As used herem, regulatmg keratmous tissue pigmentation mcludes skm lightemng Skm lightening involves diminishing, mmiimzmg and/or effacing existing melamn m skm (therapeutic), and/or delaying, minimizing and/or preventmg the formation of melamn in skm (prophylactic), including hyperpigmented regions of skm. Oxime Compound

The compositions of the present mvention comprise a safe and effective amount of an oxime compound. The oxime compound may have the following structure

M NOR³

1 « ' " 2

R¹ (NR⁶)— C-C-R² wherem -Rl and -R2 are mdependently selected from the group consisting of alkyl, aryl, and heteroaryl, wherem Rl and R2 may be covalently bonded together to form a cyclic alkyl, — M is selected from the group consisting of =0, =S, --SR4 and -OR4 (when -M is -OR4 or -SR4, there is a hydrogen bonded to the carbon to which -M is bonded) and -R4 is selected from the group consisting of hydrogen, alkyl, aryl, and heteroaryl; — R3 is selected from the group consisting of hydrogen, alkyl, aryl and heteroaryl, and l is selected from the group consisting of one and zero. When -Rl is aryl, it is preferably selected from substituted and unsubstituted, preferably unsubstituted, 2-furyl, 3-furyl, 2-thιenyl, 3-thιenyl, 2-pyrrolyl, 3-ρyrrolyl and phenyl, more preferably from 2-furyl, 2-thιenyl, 2-pyrrolyl and phenyl; more preferably 2-furyl, and especially phenyl. Also preferred are these aryl substituted with lower alkyl or lower alkoxy, especially methyl or methoxy; preferred examples mclude 4-mefhylphenyl, 4-methoxyphenyl, 5-methylfuryl, and 3,5-dιmethylfuryl.

When —Rl is alkyl, it is preferably selected from substituted and unsubstituted, preferably unsubstituted, C1-C18 alkyl, more preferably C1-C12, still more preferably C1-C8, more preferably still saturated, straight cham Cl, C2, C3, C4, C5, C6, C7 or C8.

When --R2 is aryl, it is preferably selected from substituted and unsubstituted, preferably unsubstituted, 2-furyl, 3-furyl, 2-thιenyl, 3-thιenyl, 2-pyrrolyl, 3-pyrrolyl and phenyl, more preferably from 2-furyl, 2-thιenyl, 2-pyrrolyl and phenyl; more preferably 2-furyl, and especially phenyl. Also preferred are these aryl substituted with lower alkyl or lower alkoxy, especially methyl or methoxy; preferred examples mclude 4-methylphenyl, 4-methoxyphenyl, 5-methylfuryl, and 3,5-dιmethylfuryl

When — R2 is alkyl, it is preferably selected from substituted and unsubstituted, preferably unsubstituted, C1-C18 alkyl, more preferably C1-C12, still more preferably C1-C8, more preferably still saturated, straight cham Cl, C2, C3, C4, C5, C6, C7 or C8

When — R4 is aryl, it is preferably a substituted or unsubstituted, preferably unsubstituted phenyl When -R4 is alkyl, it is preferably selected from substituted and unsubstituted, preferably unsubstituted, C1-C18, more preferably C1-C6, more preferably C1-C2, more preferably Cl --R4 is more preferably hydrogen

When — R3 is aryl, it is preferably a substituted or unsubstituted, preferably unsubstituted, phenyl When --R3 is alkyl, it is preferably selected from substituted and unsubstituted, preferably unsubstituted, C1-C18 alkyl, more preferably C1-C12, even more preferably C1-C6, still more preferably C1-C8, and even still more preferably Cl Most preferably, however,-R3 is hydrogen

When --R6 is aryl, it is preferably a substituted or unsubstituted, preferably unsubstituted, phenyl When --R6 is alkyl, it is preferably a substituted or unsubstituted, preferably unsubstituted, C1-C18 alkyl, more preferably C1-C12, more preferably C1-C6, more preferably C1-C8, more preferably Cl -R6 is more preferably hydrogen.

Preferred oxime compounds for use m the present mvention mclude syn- and anti-forms or mixtures thereof. As used herem relative to monoxime-type compounds, "anti" and "syn" refer to the positioning of the~OR3 group with respect to the ~M group In the anti position, --OR3 is proximate to — M; m the syn position, — OR3 is distal to — M Approximately equal amounts of the syn- and anti- forms of the same compound are preferred mixtures

Preferred compounds for use m the present mvention which conform to the above structural formula mclude dι-(2-furyl) ethanedione syn-monooxime, dι-(2-furyl)ethanedιone anti-monooxime, dι-(5- methyl-2-furyl) ethanedione syn-monooxime, dι-(5-ethyl-2-furyl) ethanedione syn-monooxime, dι-(4-ethyl- 2-furyl) ethanedione syn-monooxime, dι-(4-ethyl-2-furyl) ethanedione anti-monooxime, and dι-(5-ethyl-2- furyl) ethanedione anti-monooxime; more preferred are dι-(2-furyl) ethanedione syn-monooxime, dι-(2- furyl) ethanedione anti-monooxime, dι-(5-methyl-2-furyl) ethanedione syn- or anti-monooxime, dι-(5-ethyl- 2-furyl) ethanedione syn- or anti-monooxime and dι-(4-efhyl-2-furyl) ethanedione syn- or anti-monooxime, more preferred are dι-(2-furyl) ethanedione syn- or anti-monooxime, dι-(2-furyl) ethanedione anti- monooxime and dι-(5-methyl-2-furyl) ethanedione syn- or anti-monooxime, still more preferred is dι-(2- furyl) ethanedione syn- or anti-monooxime.

Compounds which are also useful m the present mvention mclude syn or anti dι-(2-furyl)-2- mercapto ethaneone oxime, syn or anti dι-(2-furyl)-2-methylmercapto ethaneone oxime, syn or anti dι-(2- furyl) thioethaneone monooxime; more preferred are syn or anti dι-(2-furyl)-2-mercapto ethaneone oxime, and syn or anti dι-(2-furyl)-2-methylmercapto ethaneone oxime, more preferred is syn or anti dι-(2-furyl)-2- mercapto ethaneone oxime

Compounds which are also useful m the present mvention mclude l-methyl-2 -phenyl ethanedione syn-monooxime, l-methyl-2-phenyl ethanedione anti-monooxime, l-ethyl-2 -phenyl ethanedione syn- monooxime, 1-ethy 1-2 -phenyl ethanedione anti-monooxime, l-n-propyl-2 -phenyl ethanedione syn- or anti-monooxime, l-n-hexyl-2-phenyl ethanedione syn- or anti-monooxime, l-methyl-2 - (4-methoxyphenyl) ethanedione syn- or anti-monooxime, l-methyl-2-(4-methylphenyl) ethanedione syn- or anti-monooxmie, l-(2-ftιryl) 2-phenyl ethanedione syn- or anti-monooxime, l-(2-thιenyl) 2-phenyl ethanedione syn- or anti-monooxime, l-(2-pyrrolyl)-2-phenyl ethanedione syn- monooxime, l-(2-pyrrolyl)-2-phenyl ethanedione anti-monooxime, l-(N-methyl-2-pyrrolyl)-2-phenyl ethanedione syn-monooxime, l-(N-methyl-2-pyrrolyl)-2-phenyl ethanedione anti-monooxmie, and 1,2-dιmethyl ethanedione syn- or anti-monooxime; more preferably l-methyl-2 -phenyl ethanedione syn- monooxime, l-mefhyl-2-phenyl ethanedione anti-monooxnne, l-ethyl-2-phenyl ethanedione syn- monooxune, l-ethyl-2-phenyl ethanedione anti-monooxime, l-n-ρropyl-2 -phenyl ethanedione syn- or anti- monooxnne, l-n-hexyl-2 -phenyl ethanedione syn- or anti-monooxime, l-methyl-2 -(4-mefhoxyphenyl) ethanedione syn- or anti-monooxmie, l-methyl-2-(4-methylphenyl) ethanedione syn- or anti-monooxmie, 1- (2-furyl) 2-phenyl ethanedione syn-monooxmie and l-(2-thιenyl) 2-phenyl ethanedione syn-monooxime, more preferred are l-mefhyl-2-phenyl ethanedione syn-monooxime, l-methyl-2 -phenyl ethanedione anti- monooxime and l-efhyl-2-phenyl ethanedione syn-monooxime; still more preferred is l-n-hexyl-2-phenyl ethanedione syn-monooxime.

Compounds which are also useful in the present mvention mclude N-phenyl-2-oxopropanamιde oxime, N-phenylmethyl-2-oxopropanarmde oxime, N-(2-furyl-5-mefhyl)-2-oxopropanamιde oxime, and N- (2-furyl)-2-oxopropanamιde oxime, more preferred are N-phenyl-2-oxopropanamιde oxime, N- phenylmethyl-2-oxopropanamιde oxrme and N-(2-furyl-5-methyl)-2-oxopropanarmde oxime; still more preferred is N-phenyl-2-oxopropanamιde oxime.

Additional oxnne compounds which are useful m the present mvention mclude lH-ιndole-2,3- dιone-3-oxime, l-methyl-ιndole-2,3-dιone-3, oxnne, l-ethyl-mdole-2,3-dιone-3-oxιme, l-propyl-ιndole-2,3- dιone-3-oxιme, l-phenyl-mdole-2,3-dιone-3-oxιme, and l-(4-ethylphenyl)-mdole-2,3-dιone-3-oxune; more preferred is lH-ιndole-2,3-dιone-3-oxιme, l-methyl-ιndole-2,3-dιone-3-oxιme and 1-ethyl- ιndole-2,3- dιone-3-oxιme, more preferred is lH-mdole-2,3-dιone-3-oxune

For oxime compounds useful m the present mvention named above, the lack of a designation of syn- or anti- is nonspecific and means either form alone or a mixture of the two.

Another preferred oxnne compound useful in the present mvention has the following structural formula'

wherem =X is =0 or =S, -R7 is hydrogen or from 0 to 5 alkyl substituents, and -R8 is C1-C8 alkyl Preferably, =S is =0. Preferably, --R7 are hydrogen or lower alkyls, more preferably C1-C3, especially methyl. Preferably -R7 are saturated when it is alkyl. Furthermore, preferably -R7 are unsubstituted and straight cham when it is alkyl. Preferred -R7 is hydrogen or a mono-substituent, preferably m the 4- position

Preferred -R8 is saturated Preferred -R8 is unsubstituted. Preferred -R8 is C1-C3, especially Cl Preferably, the oxime compound is 1 -phenyl- l,2-propanedιone-2 -oxnne.

In another embodiment of the present mvention, the oxnne compound may have the following structural formula-

wherem each X is independently O or S, --R7 is from 1 to 3 alkyl substituents, and -R8 is C4-C8 alkyl Preferred X is O Preferred -R7 are m the 3-posιtιon and/or 5-posιtιon Preferred -R7 is a mono- substituent m the 5-posιtιon; otherwise preferred -R7 and -R8 are as provided above

In another embodiment, the oxime compound useful m the present mvention has the following structure-

wherem each X is mdependently O or S, no more than one -R9 is hydrogen, and one or both -R9 are mdependently from 1 to 3 alkyl substituents Preferred X is O Preferred -R9 are lower alkyl, preferably C1-C3, especially methyl Preferred -R9 are saturated Preferred -R9 are unsubstituted. Preferred -R9 are straight cham Preferred -R9 are m the 3-posιtιon and/or the 5-posιtιon Preferred -R9 are mono- substituents m the 5-posιtιon. The oxime compound of the present mvention may also have the following α-diamine compound structural formula

wherem each --R1 is mdependently selected from the group consisting of alkyl, aryl, heteroaryl and heterocyclic, or the — Rl's are covalently bonded together to form a cyclic alkyl or heterocyclic πng, — R2 and - R3 are — OR4, m which case there is no bond or a polar bond between -R2 and the mtrogen covalently bonded to — R3, each --R4 bemg mdependently selected from the group consistmg of hydrogen, alkyl and aryl except that both --R4 's are not methyl when both -Rl 's are furyl, or -R2 is — 0~ and is covalently bonded to the nitrogen which is covalently bonded to -R3, and --R3 is —0— (there bemg a + charge on the mtrogen to which it is bonded) or ml

In another embodiment the oxime compound consists essentially of compounds wherem =NR2 and =NR3 are m amphi configuration when both --R2 and --R3 are -OH, and when both --R1 's are furyl or the --R1 's are covalently bonded together to form a cyclohexanedione structure

In any case the following measures are preferred Preferably both -Rl 's are the same moiety Preferably both — R4 's are the same moiety

When -Rl is aryl, -Rl is preferably selected from substituted and unsubstituted, preferably unsubstituted, 2-hydroxyphenyl and phenyl

When — Rl is heteroaryl, —Rl is preferably selected from substituted and unsubstituted, preferably unsubstituted, 2-furyl, 3-furyl, 2-thιenyl, 3-fhιenyl, 2-pyrrolyl, 2-ιmadazolyl, 1-pyrazolyl, 2-pyrazmyl, 2- pyπmidinyl, 3-pyπdazmyl, 3-ιsoquιnolyl, 8-puπnyl, 1-phthalazιnyl, 2-quιnoxalιnyl, 3-fiιrazanyl, 3- lsoxazolyl, 2-tetrazolyl and 5-tetrazolyl, more preferably from 2-furyl, 3-furyl, 2-thιenyl, 3-thιenyl and 2- pyrrolyl, more preferably still from 2-furyl and 3-furyl Most preferably -Rl is 2-furyl

When --R1 is heterocyclic, --R1 is preferably the saturated analog of the preferred heteroaryls specified m the previous paragraph, most preferred is 2-tetrahydrofuryl

When — Rl is alkyl, — Rl is preferably selected from substituted and unsubstituted, preferably unsubstituted, C1-C20 alkyl, more preferably C1-C18, more preferably C1-C12, more preferably still Cl- C6, more preferably C1-C2, most preferably Cl Preferred alkyl — Rl 's are alkanyls Preferred alkanyls are straight cham

When — Rl is substituted, each substituent is preferably selected from alkyl and aryl When the substituent is an alkyl, it is preferably selected from C1-C20 alkyl, more preferably C1-C18, more preferably C1-C12, more preferably still C1-C6, more preferably C1-C2, most preferably Cl When the substituent is an aryl, it is preferably phenyl

Prefeπed oxime compounds which are useful m the present mvention mclude those havmg the following α-diamine structural formula

wherem — Rl is as defined heremabove

Prefeπed oxime compounds useful m the present mvention mclude those havmg the following - diamine structural formula

wherem --R1 and -R4 are as defined heremabove In certam embodiments, such compounds are m the amphi configuration

Most preferably -R4ιs hydrogen

When — R4 is aryl, it is unsubstituted or substituted, preferably unsubstituted, preferably -R4 is phenyl

When-R4 is a substituted aryl, the substituent is preferably —OH When -R4 is alkyl, it is unsubstituted or substituted, preferably unsubstituted, preferably selected from Cl -C20, more preferably C2-C18, more preferably C2-C12, more preferably C2-C6, more preferably still C2-C4, most preferably C2 When -R4 is a substituted alkyl, prefeπed substituents are selected from —OH, =0, carboxy, — NH2, — NHR7 and -NR72, wherem --R7 is alkyl or aryl

Preferred oxnne compounds useful m the present mvention mclude dι-(2-furyι) ethanedione amphi- dioxime, dι-(5-methyl-2-furyl) ethanedione amphi-dioxime, dι-(4-methyl-2-furyl) ethanedione amphi- dioxime, dι-(5-ethyl-2-furyl) ethanedione amphi-dioxime, dι-(4-ethyl-2-furyl) ethanedione amphi-dioxime, dι-(5-propyl-2-furyl) ethanedione amphi-dioxime, and dι-(4-propyl-2-furyl) ethanedione amphi-dioxime, more prefeπed are dι-(2-furyl) ethane-dione amphi-dioxime, dι-(5-mefhyl-2-furyl) ethanedione amphidioxime, dι-(4-methyl-2-furyl) ethanedione amphi-dioxime, dι-(5-ethyl-2-furyl) ethanedione amphi- dioxime, and dι-(4-ethyl-2-furyl) ethanedione amphi-dioxime, still more prefeπed is dι-(2-furyl) ethanedione amphi-dioxime which is also refeπed to as 2-fuπldιoxιme While the amphi foπn is prefeπed, mixtures of it with other forms (anti and/or syn) can be utilized, especially mixtures with approximately equal content of amphi and anti forms As used herem, "amphi", "amphi form", and "amphi position" refer to the positioning of the — R2 and --R3 groups of the α-diamine oxime compounds relative to one another such that the --R2 and --R3 groups pomt m the same direction as opposed to anti or syn forms wherem the R2 and — R3 groups pomt in opposite dnections away from or toward each other, respectively Representative structures mclude

NOH NOH

dι-(2-furyl) ethanedione amphi-dioxime,

NOH NOH

dι-(5-methyl-2 -furyl) ethanedione amphi-dioxime, and

dι-(4-methyl-2-furyl) ethanedione amphi-dioxime Compounds also prefeπed for use in the present mvention mclude dι-(2-thιenyl) ethanedione amphi-dioxime, dι-(5-mefhyl-2-fhιenyl) ethanedione amphi-dioxime, dι-(4-methyl-2-thιenyl) ethanedione amphi-dioxime, dι-(5-ethyl-2-tmenyl) ethanedione amphi-dioxime, and dι-(5-propyl-2-thιenyl) ethanedione ampmdtoxime, more prefeπed are dι-(2-thιenyl) ethanedione amphi-dioxime, dι-(5-methyl-2-thιenyl) ethanedione amphi-dioxime, and dι-(4-mefhyl-2-tmenyl) ethanedione amphi-dioxime, still more prefeπed is dι-(2-fhιenyl) ethanedione amphi-dioxime While the amphi form is prefeπed, mixtures of it with other forms (anti and/or syn) can be utilized, especially mixtures with approximately equal content of amphi and anti forms Representative structures mclude

NOH NOH

dι-(2-thιenyl) ethanedione amphi-dioxime, NOH NOH

dι-(5-methyl-2-thιenyl) ethanedione amphi-dioxime,

dι-(4-mefhyl-2-thιenyl) ethanedione amphi-dioxime Compounds also prefeπed for use m the present mvention mclude dι-(2 -pyπolyl) ethanedione amphi-dioxime, dι-(5-methyl-2-pyrrolyl) ethanedione amphi-dioxime, dι-(4-methyl-2-pyrrolyl) ethanedione amphi-dioxnne, dι-(5-efhyl-2-pyπolyl) ethanedione amphi-dioxime, dι-(4-ethyl-2-pyrrolyl) ethanedione amphi-dioxime, dι-(5-propyl-2-pyπolyl) ethanedione ampm-dioxm e, and dι-(5-propyl-2-pyπolyl) ethanedione amphi-dioxune, more prefeπed are dι-(2-pyπolyl) ethanedione amphi-dioxime, dι-(5-methyl-2- pyπolyl) ethanedione ampm-dioxmie, dι-(4-mefhyl-2-pyπolyl) ethanedione amphi-dioxime, dι-(5-ethyl-2- pyπolyl) ethanedione amphi-dioxime, and dι-(4-ethyl-2-pyπolyl) ethanedione ampmdioxime, still more prefeπed are dι-(2-pyπolyl) ethanedione amphi-dioxime, dι-(5-methyl-2-pyrrolyl) ethanedione amphi- dioxime, and dι-(4-mefhyl-2-pyrrolyl) ethanedione amphi-dioxime, more preferred still is dι-(2-pyrrolyl) ethanedione amphi-dioxime While the amphi form is prefeπed, mixtures of it with other forms (anti and/or syn) can be utilized, especially mixtures with approximately equal content of amphi and anti forms Representative structures mclude

NOH NOH

dι-(2 -pyπolyl) ethanedione amphi-dioxime,

NOH NOH

dι-(5-mefhyl-2-pyπolyl) ethandione amphi-dioxune, and

dι-(4-methyl-2 -pyrrolyl) ethanedione amphi-dioxime Compounds also prefeπed for use m the present mvention include dι-(l-methyl-2-pyπolyl) ethanedione amphi-dioxime, dι-(l,5-dιmethyl-2 -pyπolyl) ethanedione amphi-dioxime, dι-(l-mefhyl-5-etτryl- 2-pyrrolyl) ethanedione amphi-dioxime, dι-(l-methyl-5-propyl-2 -pyrrolyl) ethanedione amphi-dioxime, and dι(l-methyl-2-pyπolyl) ethanedione amphi-dioxime, more preferred are dι-(l-mefhyl-2-pyπolyl) ethanedione amphi-dioxune, dι-(l,5-dmιethyl-2-pyrrolyl) ethanedione amphi-dioxime, dι-(l-methyl- dιmethyl-2-pyπolyl) ethanedione amphi-dioxime, dι-(l-methyl-5-ρropyl-2-pyrrolyl) ethanedione amphi- dioxime, still more prefeπed is dι-( l-methyl-2 -pyrrolyl) ethanedione amphi-dioxime While the amphi form is prefeπed, mixtures of it with other forms (anti and/or syn) can be utilized, especially mixtures with approximately equal content of amphi and anti forms Representative structures mclude

NOH NOH

dι-( l-methyl-2 -pyπolyl) ethanedione amphi-dioxune,

NOH NOH

d — (l,5-dιmethyl-2 -pyπolyl) ethanedione amphi-dioxime, and

dι-(l,4-methyl-2-pyπolyl) ethanedione amphi-dioxune Compounds also prefeπed for use m the present invention mclude

NOH NOH

dι-(2-ιmadazolyl) ethanedione amphi-dioxime,

NOH NOH

dι-(l-pyrazolyl) ethanedione amphi-dioxime,

NOH NOH

dι-(2-pyrazιnyl) ethanedione amphi-dioxime,

NOH NOH

dι-(2-pyπrmdmyl) ethanedione amphi-dioxime, NOH NOH

dι-(3-pyπdazmyl) ethanedione amphi-dioxime,

NOH NOH

-(3-ιsoqumolyl) ethanedione amphi-dioxune,

dι-(8-puπnyl) ethanedione amphi-dioxime,

NOH NOH

dι -phthalzmyl) ethanedione amphi-dioxnne,

NOH NOH

-(2-quιnoxalιnyl) ethanedione amphi-dioxime, NOH NOH

dι-(3-furazanyl) ethanedione amphi-dioxime,

NOH NOH

dι-(3-ιsoxazolyl) ethanedione amphi-dioxime,

N=N NOH NOH N=N

< / >/

N- N-N dι-(2-tetrazolyl) ethanedione amphi-dioxime,

dι-(5-tetrazolyl) ethanedione amphi-dioxime While the amphi form is prefeπed, mixtures of it with other forms (anti and/or syn) can be utilized, especially mixtures with approximately equal content of amphi and anti forms

Compounds also prefeπed for use m the present mvention mclude dι-(4-ethylphenyl) ethanedione amphi-dioxime, dι-(3-efhylphenyl) ethanedione amphi-dioxime, dι-(4-propylphenyl) ethanedione amphi- dioxime, dι-(2-hydroxy) ethanedione amphi-dioxime, and dι-(2-hydroxy-4-ethylphenyl) ethanedione amphi- dioxime; more prefeπed are dι-(4-ethylphenyl) ethanedione amphi-dioxnne, dι-(3-ethylphenyl) ethanedione amphi-dioxime, dι-(4-propylphenyl) ethanedione amphi-dioxime; still more preferred is dι-(4-ethylphenyl) ethanedione amphi-dioxime. While the amphi form is prefeπed, mixtures of it with other forms (ann and/or syn) can be utilized, especially mixtures with approximately equal content of amphi and anti forms Representative structures include-

dι-(4-ethylphenyl) ethanedione amphi-dioxime and

dι-(3-ethylphenyl) ethanedione amphi-dioxime Compounds also prefeπed for use m the present mvention mclude 4,5-dι-(2-furyl) furoxan and 4,5- dι-(2-thιenyl) furoxan, preferably 4,5-dι-(2-furyl) furoxan, a representative structure of which is as follows

4,5-dι-(2-furyl) furoxan, Also prefeπed for incorporation m the compositions of the present mvention are mixtures of any of the above compounds

A compound also prefeπed for use m the present mvention is amphi- 1 ,2-cyclohexanedιone, which is represented by the following structure

NOH NOH

CH₇ CH, amphi- 1 ,2-cyclohexanedιone While the amphi form is prefeπed, mixtures of it with other forms (anti and/or syn) can be utilized, especially mixtures with approximately equal content of amphi and anti forms

Also prefeπed for incorporation m the compositions of the present mvention are mixtures of the above oxnne compounds Typically such mixtures are about half amphi-form and about half anti-form with very little (less than about 2%) syn- form For compounds named herem, lack of designation of a particular form is non-specific and denotes either the amphi-form alone or a mixture of it with the other forms, any such mixture is preferably at least 40% amphi-form, more preferably at least 60% amphi-form, more preferably still at least 80% amphi-form

Another aspect of the present mvention relates to oxnne compounds havmg the α-diamine structural formula

wherem -R4 is as defined as herembefore, ~B is mdependently selected from the group consistmg of alkyl, aryl, or heteroaryl, preferably alkyl, more preferably C2-C20 alkyl, more preferably a C2-C6 alkyl, more preferably ethyl ~B is preferably bonded to the 4-posιtιon

Another aspect of the present mvention relates to oxnne compounds havmg the α-diaimne structural formula

wherem -R4 and ~B are as defined herembefore, ~B is preferably bonded to the 5-posιtιon

Another aspect of the present mvention relates to oxime compounds havmg the structural formula

wherem -R4 and — B are as defined herembefore, — B is preferably bonded to the 5-posιtιon

Most prefeπed oxnne compounds of the present mvention are selected from the group consistmg of dι-(2-furyl) ethanedione syn-monooxime, dι-(2-furyl) ethanedione anti-monooxime, dι-(2-furyl) ethanedione amphi-dioxime, dι-(2-furyl) ethanedione syn-dioxime, dι-(2-furyl) ethanedione anti-dioxime, 1- phenyl-l,2-propanedιone-2-oxιme, and combinations thereof Compositions of this mvention preferably contam from about 0 001% to about 20%, of the oxime compound, more preferably from or about 0 01% to about 10%, even more preferably from about 0.1% to about 5%, and most preferably from about 0.5% to about 5%, by weight of the composition. Dermatologically Acceptable Carner

The topical compositions of the present mvention also compnse a dermatologically acceptable carner for the oxime compound The phrase "dermatologically acceptable earner", as used herem, means that the carner is suitable for topical application to mammalian keratinous tissue, has good aesthetic properties, is compatible with the actives of the present mvention and any other components, and will not cause any untoward safety or toxicity concerns. A safe and effective amount of earner is from about 50% to about 99.99%, preferably from about 80% to about 99 9%, more preferably from about 90% to about 98%, and most preferably from about 90%) to about 95% of the composition.

The carner can be m a wide vanety of forms For example, emulsion earners, mcludmg, but not limited to, oil-in-water, water-in-oύ, water-m-oil-in-water, and oil-in-water-in-silicone emulsions, are useful herem

Prefeπed earners compnse an emulsion such as oil-in-water emulsions, water-m-oil emulsions, and water-m-sihcone emulsions. As will be understood by the skilled artisan, a given component will distribute primarily mto either the water or oil/sihcone phase, dependmg on the water solubύity/dispersibility of the component m the composition The oxime compound distributes pnmanly mto the oil phase. Oil-in-water emulsions are especially prefeπed.

Emulsions accordmg to the present invention generally contam a solution as described above and a lipid or oil Lipids and oils may be denved from animals, plants, or petroleum and may be natural or synthetic (i.e., man-made). Prefeπed emulsions also contam a humectant, such as glycerin. Emulsions will preferably further contam from about 1% to about 10%, more preferably from about 2% to about 5%, of an emulsifier, based on the weight of the carner. Emulsifiers may be nonionic, anionic or canonic. Suitable emulsifiers are disclosed m, for example, U.S. Patent 3,755,560, issued August 28, 1973, Dickert et al.; U.S Patent 4,421,769, issued December 20, 1983, Dixon et al , and McCutcheon's Detergents and Emulsifiers, North American Edition, pages 317-324 (1986).

The emulsion may also contam an anti-foaming agent to minimize foaming upon application to the keratmous tissue. Ann-foaming agents mclude high molecular weight sihcones and other matenals well known in the art for such use.

Suitable emulsions may have a wide range of viscosities, dependmg on the desned product form Exemplary low viscosity emulsions, which are prefeπed, have a viscosity of about 50 centistokes or less, more preferably about 10 centistokes or less, most preferably about 5 centistokes or less.

Prefeπed water-m-sihcone and oil-in-water emulsions are descnbed m greater detail below a) Water-in-silicone emulsion

Water-in-sihcone emulsions contam a continuous sihcone phase and a dispersed aqueous phase. (1) Continuous silicone phase

Prefeπed water-m-sihcone emulsions of the present mvention comprise from about 1% to about 60%), preferably from about 5% to about 40%, more preferably from about 10% to about 20%, by weight of a contmuous silicone phase The continuous silicone phase exists as an external phase that contains or surrounds the discontinuous aqueous phase descnbed hereinafter

The contmuous silicone phase contains a polyorganosiloxane oil A prefeπed water-in-sihcone emulsion system is formulated to provide an oxidatively stable vehicle for the optional retinoid The continuous silicone phase of these prefeπed emulsions compnses between about 50% and about 99 9% by weight of organopolysiloxane oil and less than about 50% by weight of a non-silicone oil In an especially prefeπed embodiment, the contmuous silicone phase compnses at least about 50%, preferably from about 60% to about 99 9%, more preferably from about 70% to about 99 9%, and even more preferably from about 80% to about 99 9%, polyorganosiloxane oil by weight of the contmuous silicone phase, and up to about 50%) non-silicone oils, preferably less about 40%, more preferably less than about 30%, even more preferably less than about 10%, and most preferably less than about 2%, by weight of the contmuous silicone phase Concentrations of non-silicone oils m the continuous silicone phase are minimized or avoided altogether so as to further enhance oxidative stability of the selected retinoid m the compositions Water-in-sihcone emulsions of this type are described m copendmg U S Patent Application Senal No 08/570,275, filed December 11, 1995, m the names of Joseph Michael Zukowski, Brent William Mason, Larry Richard Robmson and Greg George Hillebrand

The organopolysiloxane oil for use m the composition may be volatile, non-volatile, or a mixture of volatile and non-volatile silicones The term "nonvolatile" as used m this context refers to those sihcones that are liquid under ambient conditions and have a flash pomt (under one atmosphenc of pressure) of or greater than about 100°C The term "volatile" as used in this context refers to all other silicone oils Suitable organopolysiloxanes can be selected from a wide vanety of sihcones spanning a broad range of volatilities and viscosities Examples of suitable organopolysiloxane oils mclude polyalkylsiloxanes, cyclic polyalkylsiloxanes, and polyalkylarylsiloxanes

Polyalkylsiloxanes useful in the composition herem mclude polyalkylsiloxanes with viscosities of from about 0 5 to about 1,000,000 centistokes at 25°C Such polyalkylsiloxanes can be represented by the general chemical formula R3SιO[R2SιO]xSιR3 wherein R is an alkyl group havmg from one to about 30 carbon atoms (preferably R is methyl or ethyl, more preferably methyl, also mixed alkyl groups can be used m the same molecule), and x is an integer from 0 to about 10,000, chosen to achieve the desired molecular weight which can range to over about 10,000,000 Commercially available polyalkylsiloxanes mclude the polydimefhylsiloxanes, which are also known as dimethicones, examples of which mclude the Vicasil® senes sold by General Electnc Company and the Dow Corning® 200 senes sold by Dow Corning Corporation Specific examples of suitable polydimethylsiloxanes mclude Dow Corning® 200 fluid havmg a viscosity of 0 65 centistokes and a boiling pomt of 100°C, Dow Corning® 225 fluid havmg a viscosity of 10 centistokes and a boilmg pomt greater than 200°C, and Dow Corning® 200 fluids havmg viscosities of 50, 350, and 12,500 centistokes, respectively, and boilmg pomts greater than 200°C. Suitable dimethicones mclude those represented by the chemical formula (CH3)3SιO[(CH3)2SιO]x[CH3RSιO]ySι(CH3)3 wherem R is straight or branched cham alkyl havmg from two to about 30 carbon atoms and x and y are each mtegers of 1 or greater selected to achieve the desned molecular weight which can range to over about 10,000,000 Examples of these alkyl-substituted dimethicones mclude cetyl dimethicone and lauryl dimethicone.

Cyclic polyalkylsiloxanes suitable for use m the composition mclude those represented by the chemical formula [SιR2-0]n wherem R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl) and n is an mteger from about 3 to about 8, more preferably n is an mteger from about 3 to about 7, and most preferably n is an mteger from about 4 to about 6. When R is methyl, these matenals are typically refeπed to as cyclomethicones Commercially available cyclometmcones include Dow Corning® 244 fluid havmg a viscosity of 2 5 centistokes, and a boilmg pomt of 172°C, which primarily contams the cyclomethicone tetramer (1 e n=4), Dow Corning® 344 fluid havmg a viscosity of 2.5 centistokes and a boilmg pomt of 178°C, which primarily contams the cyclomethicone pentamer (i.e n=5), Dow Corning® 245 fluid havmg a viscosity of 4.2 centistokes and a boilmg pomt of 205°C, which pnmanly contains a mixture of the cyclomethicone tetramer and pentamer (i.e. n=4 and 5), and Dow Corning® 345 fluid havmg a viscosity of 4.5 centistokes and a boilmg pomt of 217°, which primarily contams a mixture of the cyclomethicone tetramer, pentamer, and hexamer (i.e. n=4, 5, and 6)

Also useful are matenals such as tnmethylsiloxysilicate, which is a polymeric matenal coπesponding to the general chemical formula [(CH2)3Sι01/2]x[Sι02]y, wherem x is an mteger from about 1 to about 500 and y is an mteger from about 1 to about 500 A commercially available tnmethylsiloxysilicate is sold as a mixture with dimethicone as Dow Corning® 593 fluid

Dimefhiconols are also suitable for use m the composition These compounds can be represented by the chemical formulas R3SιO[R2SιO]xSιR20H and HOR2SιO[R2SιO]xSιR20H wherem R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl) and x is an mteger from 0 to about 500, chosen to achieve the desned molecular weight. Commercially available dimefhiconols are typically sold as mixtures with dimethicone or cyclomethicone (e.g. Dow Corning® 1401, 1402, and 1403 fluids).

Polyalkylaryl siloxanes are also suitable for use m the composition Polymethylphenyl siloxanes havmg viscosities from about 15 to about 65 centistokes at 25°C are especially useful.

Prefened for use herem are organopolysiloxanes selected from the group consistmg of polyalkylsiloxanes, alkyl substituted dimethicones, cyclomethicones, tnmethylsiloxysihcates, dimefhiconols, polyalkylaryl siloxanes, and mixtures thereof More prefeπed for use herem are polyalkylsiloxanes and cyclomethicones. Prefeπed among the polyalkylsiloxanes are dimethicones

As stated above, the contmuous silicone phase may contam one or more non-silicone oils. Suitable non-silicone oils have a melting pomt of about 25°C or less under about one atmosphere of pressure Examples of non-silicone oils suitable for use m the contmuous silicone phase are those well known m the chemical arts m topical personal care products m the form of water-m-oil emulsions, e g , mineral oil, vegetable oils, synthetic oils, semisynthetic oils, etc (n) Dispersed aqueous phase

The topical compositions of the present mvention compnse from about 30% to about 90%, more preferably from about 50% to about 85%, and most preferably from about 70% to about 80% of a dispersed aqueous phase In emulsion technology, the term "dispersed phase" is a term well-known to one skilled m the art which means that the phase exists as small particles or droplets that are suspended m and surrounded by a contmuous phase The dispersed phase is also known as the internal or discontinuous phase The dispersed aqueous phase is a dispersion of small aqueous particles or droplets suspended m and surrounded by the continuous silicone phase described herembefore

The aqueous phase can be water, or a combmation of water and one or more water soluble or dispersible ingredients Noidimihng examples of such optional ingredients mclude thickeners, acids, bases, salts, chelants, gums, water-soluble or dispersible alcohols and polyols, buffers, preservatives, sunscreening agents, colormgs, and the like

The topical compositions of the present mvention will typically comprise from about 25% to about 90%, preferably from about 40% to about 80%, more preferably from about 60%> to about 80%, water in the dispersed aqueous phase by weight of the composition

(m) Emulsifier for dispersmg the aqueous phase The water-in-sihcone emulsions of the present mvention preferably compnse an emulsifier In a prefeπed embodiment, the composition contams from about 0 1% to about 10% emulsifier, more preferably from about 0 5% to about 7 5%, most preferably from about 1% to about 5%, emulsifier by weight of the composition The emulsifier helps disperse and suspend the aqueous phase within the contmuous silicone phase

A wide vanety of emulsifying agents can be employed herem to form the prefeπed water-in-sihcone emulsion Known or conventional emulsifying agents can be used m the composition, provided that the selected emulsifying agent is chemically and physically compatible with essential components of the composition, and provides the desired dispersion charactenshcs Suitable emulsifiers mclude silicone emulsifiers, non-sihcon-containing emulsifiers, and mixtures thereof, known by those skilled m the art for use in topical personal care products Preferably these emulsifiers have an HLB value of or less than about 14, more preferably from about 2 to about 14, and most preferably from about 4 to about 14 Emulsifiers havmg an HLB value outside of these ranges can be used m combmation with other emulsifiers to achieve an effective weighted average HLB for the combmation that falls within these ranges

Silicone emulsifiers are prefeπed A wide vanety of silicone emulsifiers are useful herem These silicone emulsifiers are typically organically modified organopolysiloxanes, also known to those skilled m the art as silicone surfactants Useful silicone emulsifiers mclude dimethicone copolyols These matenals are polydimethyl siloxanes which have been modified to mclude polyether side chains such as polyethylene oxide chams, polypropylene oxide chains, mixtures of these chams, and polyether chams contammg moieties denved from both ethylene oxide and propylene oxide Other examples mclude alkyl-modified dimethicone copolyols, 1 e , compounds which contam C2-C30 pendant side chams Still other useful dimethicone copolyols mclude matenals havmg vanous cationic, anionic, amphoteπc, and zwittenomc pendant moieties

The dimethicone copolyol emulsifiers useful herem can be descnbed by the following general structure

CH₃ CH₃ CH₃ CH₃ CH₃ I I I I CH — Si— O -Si— -O -Si— -O -Si- -o -Si— CH₃ I I I , I

CH₃ CH₃ R R2 CH₃

wherem R is C1-C30 straight, branched, or cyclic alkyl and R2 is selected from the group consisting of

"(CH2)n~0--(CH2CHR30)m~H, and

~(CH2)n-0~(CH2CHR30)m-(CH2CHR40)o~H, wherem n is an mteger from 3 to about 10, R3 and R4 are selected from the group consistmg of H and Cl- C6 straight or branched cham alkyl such that R3 and R4 are not simultaneously the same, and m, o, x, and y are selected such that the molecule has an overall molecular weight from about 200 to about 10,000,000, with m, o, x, and y bemg mdependently selected from mtegers of zero or greater such that m and o are not both simultaneously zero, and z bemg mdependently selected from mtegers of 1 or greater It is recognized that positional isomers of these copolyols can be achieved The chemical representations depicted above for the R2 moieties contammg the R3 and R4 groups are not meant to be limiting but are shown as such for convenience

Also useful herem, although not stnctly classified as dimethicone copolyols, are silicone surfactants as depicted m the structures m the previous paragraph wherem R2 is

~(CH2)n~0-R5, wherem R5 is a canonic, amomc, amphoteπc, or zwittenomc moiety

Nominating examples of dimethicone copolyols and other silicone surfactants useful as emulsifiers herem mclude polydimethylsiloxane polyether copolymers with pendant polyethylene oxide sidechams, polydimethylsiloxane polyether copolymers with pendant polypropylene oxide sidechams, polydimethylsiloxane polyether copolymers with pendant mixed polyethylene oxide and polypropylene oxide sidechams, polydimethylsiloxane polyether copolymers with pendant mixed poly(ethylene)(propylene)oxιde sidechams, polydimethylsiloxane polyether copolymers with pendant organobetaine sidechams, polydimethylsiloxane polyether copolymers with pendant carboxylate sidechams, polydimethylsiloxane polyether copolymers with pendant quaternary ammonium sidechams, and also further modifications of the precedmg copolymers contammg pendant C2-C30 straight, branched, or cyclic alkyl moieties Examples of commercially available dimethicone copolyols useful herem sold by Dow Corning Corporation are Dow Corning® 190, 193, Q2-5220, 2501 Wax, 2-5324 fluid, and 3225C (this later matenal bemg sold as a mixture with cyclomethicone) Cetyl dimethicone copolyol is commercially available as a mixture with polyglyceryl-4 isostearate (and) hexyl laurate and is sold under the tradename ABIL® WE-09 (available from Goldschmidt) Cetyl dimethicone copolyol is also commercially available as a mixture with hexyl laurate (and) polyglyceryl-3 oleate (and) cetyl dimethicone and is sold under the tradename ABIL® WS-08 (also available from Goldschmidt) Other nonlimiting examples of dimethicone copolyols also mclude lauryl dimethicone copolyol, dimethicone copolyol acetate, diemethicone copolyol adipate, dimethicone copolyolamine, dimethicone copolyol behenate, dimethicone copolyol butyl ether, dimethicone copolyol hydroxy stearate, dimethicone copolyol isostearate, dimethicone copolyol laurate, dimethicone copolyol methyl ether, dimethicone copolyol phosphate, and dimethicone copolyol stearate See International Cosmetic Ingredient Dictionary, Fifth Edition, 1993

Dimethicone copolyol emulsifiers useful herem are descπbed, for example, m U S Patent No 4,960,764, to Figueroa, Jr et al , issued October 2, 1990, European Patent No EP 330,369, to SanoGueira, published August 30, 1989, G H Dahms, et al , "New Formulation Possibilities Offered by Silicone Copolyols," Cosmetics & Toiletries, vol 110, pp 91-100, March 1995, M E Carlotti et al , "Optimization of W/O-S Emulsions And Study Of The Quantitative Relationships Between Ester Structure And Emulsion Properties," J Dispersion Science And Technology, 13(3), 315-336 (1992), P Hameyer, "Comparative Technological Investigations of Orgamc and Organosihcone Emulsifiers m Cosmetic Water-m-Oil Emulsion Preparations," HAPPI 28(4), pp 88-128 (1991), J Smid-Korbar et al , "Efficiency and usability of silicone surfactants m emulsions," Provisional Communication, International Journal of Cosmetic Science, 12, 135-139 (1990), and D G Krzysύc et al , "A New Silicone Emulsifier For Water-m-Oil Systems," Drug and Cosmetic Industry, vol 146(4) pp 28-81 (Apnl 1990)

Among the non-sihcone-containing emulsifiers useful herem are vanous non-iomc and amomc emulsifying agents such as sugar esters and polyesters, alkoxylated sugar esters and polyesters, C1-C30 fatty acid esters of C1-C30 fatty alcohols, alkoxylated denvatives of C1-C30 fatty acid esters of C1-C30 fatty alcohols, alkoxylated ethers of C1-C30 fatty alcohols, polyglyceryl esters of C1-C30 fatty acids, C1-C30 esters of polyols, C1-C30 ethers of polyols, alkyl phosphates, polyoxyalkylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps, and mixtures thereof Other suitable emulsifiers are descnbed, for example, m McCutcheon's, Detergents and Emulsifiers, North Amencan Edition (1986), published by Allured Publishing Corporation, U S Patent No 5,011,681 to Ciotti et al , issued Apnl 30, 1991, U S Patent No 4,421,769 to Dixon et al , issued December 20, 1983, and U S Patent No 3,755,560 to Dickert et al , issued August 28, 1973

Nonlimiting examples of these non-sihcone-containing emulsifiers mclude polyethylene glycol 20 sorbitan monolaurate (Polysorbate 20), polyethylene glycol 5 soya sterol, Steareth-20, Ceteareth-20, PPG-2 methyl glucose ether distearate, Cetefh-10, Polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanolamme cetyl phosphate, Polysorbate 60, glyceryl stearate, PEG- 100 stearate, polyoxyethylene 20 sorbitan tnoleate (Polysorbate 85), sorbitan monolaurate, polyoxyethylene 4 lauryl ether sodium stearate, polyglyceryl-4 isostearate, hexyl laurate, steareth-20, ceteareth-20, PPG-2 methyl glucose ether distearate, ceteth-10, diethanolamine cetyl phosphate, glyceryl stearate, PEG- 100 stearate, and mixtures thereof b) Oil-in- Water Emulsions

Other preferred topical earners mclude oil-in-water emulsions, havmg a contmuous aqueous phase and a hydrophobic, water-insoluble phase ("oil phase") dispersed therein Examples of suitable earners compnsing oil-m-water emulsions are described m U S Pat No 5,073,371, to Turner, D J et al , issued Dec 17, 1991, and U S Pat No 5,073,372, to Turner, D J et al , issued Dec 17, 1991 An especially preferred oil-in-water emulsion, contammg a structunng agent, hydrophilic surfactant and water, is descnbed m detail hereinafter

(l) Structunng Agent

A prefeπed oil-in-water emulsion compnses a structunng agent to assist m the formation of a liquid crystalline gel network structure Without bemg limited by theory, it is believed that the structunng agent assists m providmg rheological charactenstics to the composition which contribute to the stability of the composition The structunng agent may also function as an emulsifier or surfactant Prefeπed compositions of this mvention comprise from about 0 5% to about 20%, more preferably from about 1% to about 10%, most preferably from about 1% to about 5%, by weight of the composition, of a structunng agent

The preferred structunng agents of the present mvention are selected from the group consisting of steanc acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, steanc acid, palmitic acid, the polyethylene glycol ether of stearyl alcohol havmg an average of about 1 to about 21 ethylene oxide units, the polyethylene glycol ether of cetyl alcohol havmg an average of about 1 to about 5 ethylene oxide units, and mixtures thereof More prefeπed structunng agents of the present mvention are selected from the group consistmg of stearyl alcohol, cetyl alcohol, behenyl alcohol, the polyethylene glycol ether of stearyl alcohol havmg an average of about 2 ethylene oxide units (steareth-2), the polyethylene glycol ether of stearyl alcohol havmg an average of about 21 ethylene oxide units (steareth-21), the polyethylene glycol ether of cetyl alcohol havmg an average of about 2 ethylene oxide units, and mixtures thereof Even more prefeπed structunng agents are selected from the group consistmg of steanc acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, steareth-2, steareth-21, and mixtures thereof (n) Hydrophilic surfactant

The preferred oil-in- water emulsions compnse from about 0 05% to about 10%, preferably from about 1% to about 6%, and more preferably from about 1% to about 3% of at least one hydrophilic surfactant which can disperse the hydrophobic matenals m the water phase (percentages by weight of the topical carner) The surfactant, at a minimum, must be hydrophilic enough to disperse m water

Suitable surfactants mclude any of a wide vanety of known catiomc, anionic, zwittenomc, and amphotenc surfactants See, McCutcheon's, Detergents and Emulsifiers, North Amencan Edition (1986), published by Allured Publishing Corporation; U.S. Patent 5,011,681 ; U.S. Patent 4,421,769; and U.S. Patent 3,755,560; these references are incorporated herem by reference m their entirety.

The exact surfactant chosen will depend upon the pH of the composition and the other components present.

Prefeπed are catiomc surfactants, especially dialkyl quaternary ammonium compounds, examples of which are descnbed m U.S. Patent 5,151,209; U.S. Patent 5,151,210, U.S. Patent 5,120,532; U.S. Patent 4,387,090, U.S. Patent 3,155,591 ; U.S. Patent 3,929,678; U.S. Patent 3,959,461; McCutcheon's, Detergents & Emulsifiers, (North American edition 1979) M.C. Publishing Co.; and Schwartz, et al., Surface Active Agents, Their Chemistry and Technology, New York: Interscience Publishers, 1949; which descnptions are incorporated herem by reference. The catiomc surfactants useful herem mclude catiomc ammonium salts such as those havmg the formula:

wherem Rl, is an alkyl group havmg from about 12 to about 30 carbon atoms, or an aromatic, aryl or alkaryl group havmg from about 12 to about 30 carbon atoms; R2, R3, and R4 are mdependently selected from hydrogen, an alkyl group havmg from about 1 to about 22 carbon atoms, or aromatic, aryl or alkaryl groups havmg from about 12 to about 22 carbon atoms; and X is any compatible amon, preferably selected from the group consisting of chlonde, bromide, iodide, acetate, phosphate, nitrate, sulfate, methyl sulfate, ethyl sulfate, tosylate, lactate, citrate, glycolate, and mixtures thereof Additionally, the alkyl groups of Rl, R2, R3, and R4 can also contam ester and/or ether linkages, or hydroxy or ammo group substituents (e.g., the alkyl groups can contam polyethylene glycol and polypropylene glycol moieties).

More preferably, Rl is an alkyl group havmg from about 12 to about 22 carbon atoms, R2 is selected from H or an alkyl group havmg from about 1 to about 22 carbon atoms; R3 and R4 are mdependently selected from H or an alkyl group havmg from about 1 to about 3 carbon atoms; and X is as descnbed previously.

Most preferably, Rl is an alkyl group havmg from about 12 to about 22 carbon atoms; R2, R3, and R4 are selected from H or an alkyl group havmg from about 1 to about 3 carbon atoms; and X is as described previously.

Alternatively, other useful catiomc emulsifiers mclude amino-amides, wherem m the above structure Rl is alternatively R5CONH-(CH2)n, wherem R5 is an alkyl group havmg from about 12 to about 22 carbon atoms, and n is an mteger from about 2 to about 6, more preferably from about 2 to about 4, and most preferably from about 2 to about 3 Nonlrmitmg examples of these catiomc emulsifiers mclude stearamidopropyl PG-dimonium chlonde phosphate, behenamidopropyl PG dimonium chlonde, stearamidopropyl ethyldimomum ethosulfate, stearamidopropyl dimethyl (mynstyl acetate) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyl dimethyl ammonium chlonde, stearamidopropyl dimethyl ammomum lactate, and mixtures thereof Especially prefeπed is behenamidopropyl PG dtmonium chlonde.

Nonlmritmg examples of quaternary ammomum salt catiomc surfactants mclude those selected from the group consisting of cetyl ammomum chlonde, cetyl ammomum bromide, lauryl ammomum chlonde, lauryl ammomum bromide, stearyl ammomum chlonde, stearyl ammomum bromide, cetyl dimethyl ammomum chlonde, cetyl dimethyl ammomum bromide, lauryl dimethyl ammomum chlonde, lauryl dimethyl ammonium bromide, stearyl dimethyl ammomum chlonde, stearyl dimethyl ammomum bromide, cetyl tnmethyl ammomum chlonde, cetyl tnmethyl ammomum bromide, lauryl tnmethyl ammomum chlonde, lauryl tnmethyl ammomum bromide, stearyl tnmethyl ammomum chlonde, stearyl tnmethyl ammomum bromide, lauryl dimethyl ammomum chlonde, stearyl dimethyl cetyl ditallow dimethyl ammomum chloride, dicetyl ammomum chlonde, dicetyl ammomum bromide, dilauryl ammomum chloride, dilauryl ammomum bromide, distearyl ammomum chloride, distearyl ammomum bromide, dicetyl methyl ammomum chloride, dicetyl methyl ammomum bromide, dilauryl methyl ammomum chlonde, dilauryl methyl ammomum bromide, distearyl methyl ammomum chlonde, distearyl methyl ammomum bromide, and mixtures thereof. Additional quaternary ammonium salts mclude those wherem the C12 to C30 alkyl carbon cham is derived from a tallow fatty acid or from a coconut fatty acid The term "tallow" refers to an alkyl group denved from tallow fatty acids (usually hydrogenated tallow fatty acids), which generally have mixtures of alkyl chains in the C16 to C18 range. The term "coconut" refers to an alkyl group denved from a coconut fatty acid, which generally have mixtures of alkyl chams ιn the C12 to C14 range. Examples of quaternary ammonium salts denved from these tallow and coconut sources mclude ditallow dimethyl ammomum chlonde, ditallow dimethyl ammomum methyl sulfate, di(hydrogenated tallow) dimethyl ammomum chloride, dι(hydrogenated tallow) dimethyl ammonium acetate, ditallow dipropyl ammomum phosphate, ditallow dimethyl ammomum nitrate, dι(coconutalkyl)dιmethyl ammonium chlonde, dι(coconutalkyl)dιmethyl ammomum bromide, tallow ammomum chlonde, coconut ammomum chlonde, stearamidopropyl PG-dimomum chlonde phosphate, stearamidopropyl ethyldmiomum ethosulfate, stearamidopropyl dimethyl (mynstyl acetate) ammomum chlonde, stearamidopropyl dimethyl cetearyl ammomum tosylate, stearamidopropyl dimethyl ammonium chlonde, stearamidopropyl dimethyl ammomum lactate, and mixtures thereof. An example of a quaternary ammomum compound havmg an alkyl group with an ester linkage is ditallowyl oxyethyl dimethyl ammomum chlonde.

More preferred catiomc surfactants are those selected from the group consisting of behenamidopropyl PG dimonium chlonde, dilauryl dimethyl ammomum chlonde, distearyl dimethyl ammomum chlonde, dimynstyl dimethyl ammomum chlonde, dipalmityl dimethyl ammomum chlonde, distearyl dimethyl ammomum chlonde, stearamidopropyl PG-dimonium chlonde phosphate, stearamidopropyl ethyldiammomum ethosulfate, stearamidopropyl dimethyl (mynstyl acetate) ammomum chlonde, stearamidopropyl dimethyl cetearyl ammomum tosylate, stearamidopropyl dimethyl ammomum chloride, stearamidopropyl dimethyl ammomum lactate, and mixtures thereof. Most preferred catiomc surfactants are those selected from the group consistmg of behenamidopropyl PG dimonium chlonde, dilauryl dimethyl ammomum chlonde, distearyl dimethyl ammomum chlonde, dimynstyl dimethyl ammomum chlonde, dipalmityl dimethyl ammomum chlonde, and mixtures thereof

A prefeπed combmation of catiomc surfactant and structunng agent is behenamidopropyl PG dimomum chlonde and/or behenyl alcohol, wherem the ratio is preferably optimized to maintained to enhance physical and chemical stability, especially when such a combmation contams lomc and/or highly polar solvents This combination is especially useful for delivery of sunscreenmg agents such as zmc oxide and octyl methoxycinnamate

A wide variety of amomc surfactants are also useful herem See, e g , U S Patent No 3,929,678, to Laughlin et al , issued December 30, 1975, which is incorporated herem by reference m its entirety Nonlimmng examples of amomc surfactants mclude the alkoyl lsefhionates, and the alkyl and alkyl ether sulfates The alkoyl lsefhionates typically have the formula RCO-OCH2CH2S03M wherem R is alkyl or alkenyl of from about 10 to about 30 carbon atoms, and M is a water-soluble cation such as ammomum, sodium, potassium and tnethanolamme Nominating examples of these lsethionates mclude those alkoyl lsethionates selected from the group consistmg of ammomum cocoyl lsethionate, sodium cocoyl lsethionate, sodium lauroyl lsethionate, sodium stearoyl lsethionate, and mixtures thereof

The alkyl and alkyl ether sulfates typically have the respective formulae ROS03M and RO(C2H40)xS03M, wherem R is alkyl or alkenyl of from about 10 to about 30 carbon atoms, x is from about 1 to about 10, and M is a water-soluble cation such as ammomum, sodium, potassium and tnethanolamme Another suitable class of amomc surfactants are the water-soluble salts of the orgamc, sulfunc acid reaction products of the general formula

R1-S03-M wherem Rl is chosen from the group consistmg of a straight or branched cham, saturated aliphatic hydrocarbon radical havmg from about 8 to about 24, preferably about 10 to about 16, carbon atoms, and M is a cation Still other amomc synthetic surfactants mclude the class designated as succinamates, olefin sulfonates havmg about 12 to about 24 carbon atoms, and β-alkyloxy alkane sulfonates Examples of these matenals are sodium lauryl sulfate and ammomum lauryl sulfate

Other amomc matenals useful herem are soaps (I e alkali metal salts, e g , sodium or potassium salts) of fatty acids, typically havmg from about 8 to about 24 carbon atoms, preferably from about 10 to about 20 carbon atoms The fatty acids used m making the soaps can be obtamed from natural sources such as, for instance, plant or ammal-denved glycendes (e g , palm oil, coconut oil, soybean oil, castor oil, tallow, lard, etc ) The fatty acids can also be synthetically prepared Soaps are descnbed m more detail m U S Patent No 4,557,853

Amphotenc and zwittenomc surfactants are also useful herem Examples of amphoteπc and zwittenomc surfactants which can be used m the compositions of the present mvention are those which are broadly descnbed as denvatives of aliphatic secondary and tertiary amines m which the aliphatic radical can be straight or branched cham and wherem one of the aliphatic substituents contams from about 8 to about 22 carbon atoms (preferably C8 - C18) and one contams an amomc water solubilizmg group, e g , carboxy, sulfonate, sulfate, phosphate, or phosphonate Examples are alkyl rmino acetates, and lminodialkanoates and aminoalkanoates of the formulas RN[CH2)mC02M]2 and RNH(CH2)mC02M wherem m is from 1 to 4, R is a C8-C22 alkyl or alkenyl, and M is H, alkali metal, alkaline earth metal ammomum, or alkanolammomum Also mcluded are nnidazolmium and ammomum denvatives Specific examples of suitable amphotenc surfactants mclude sodium 3-dodecyl-aminopropionate, sodium 3-dodecylamιnopropane sulfonate, N-alkyltaunnes such as the one prepared by reacting dodecylamme with sodium lsethionate accordmg to the teachmg of U S Patent 2,658,072 which is incorporated herem by reference m its entirety, N-higher alkyl aspartic acids such as those produced accordmg to the teachmg of U S Patent 2,438,091 which is incorporated herem by reference m its entirety, and the products sold under the trade name "Miranol" and descnbed m U S Patent 2,528,378, which is incorporated herem by reference m its entirety Other examples of useful amphoteπcs mclude phosphates, such as coamidopropyl PG-dimomum chlonde phosphate (commercially available as Monaquat PTC, from Mona Corp )

Also useful herem as amphotenc or zwittenomc surfactants are the betames Examples of betames mclude the higher alkyl betames, such as coco dimethyl carboxymethyl betaine, lauryl dimethyl carboxymefhyl betaine, lauryl dimethyl alphacarboxyethyl betame, cetyl dimethyl carboxymethyl betaine, cetyl dimethyl betame (available as Lonzaine 16SP from Lonza Corp ) lauryl bιs-(2-hydroxyethyl) carboxymethyl betame, stearyl bιs-(2-hydroxypropyl) carboxymethyl betame, oleyl dimethyl gamma-carboxypropyl betame, lauryl bιs-(2-hydroxypropyl)alpha-carboxyethyl betame, coco dimethyl sulfopropyl betame, stearyl dimethyl sulfopropyl betame, lauryl dimethyl sulfoethyl betame, lauryl bis-(2-hydroxyefhyl) sulfopropyl betame, and amidobetaines and amidosulfobetaines (wherem the RCONH(CH2)3 radical is attached to the nitrogen atom of the betame), oleyl betame (available as amphotenc Velvetex OLB-50 from Henkel), and cocamidopropyl betame (available as Velvetex BK-35 and BA-35 from Henkel)

Other useful amphotenc and zwittenomc surfactants mclude the sultames and hydroxysultames such as cocamidopropyl hydroxysultaine (available as Mirataine CBS from Rhone-Poulenc), and the alkanoyl sarcosinates coπespondmg to the formula RCON(CH3)CH2CH2C02M wherem R is alkyl or alkenyl of about 10 to about 20 carbon atoms, and M is a water-soluble cation such as ammomum, sodium, potassium and tnalkanolamme (e g , tnethanolamme), a preferred example of which is sodium lauroyl sarcosinate (m) Water

The prefeπed oil-in-water emulsion compnses from about 25% to about 98%, preferably from about 65% to about 95%, more preferably from about 70% to about 90%> water by weight of the topical carner

The hydrophobic phase is dispersed m the contmuous aqueous phase The hydrophobic phase may contam water insoluble or partially soluble matenals such as are known m the art, mcludmg but not limited to the sihcones descnbed herem m reference to sihcone-in-water emulsions, and other oils and hpids such as descnbed above m reference to emulsions.

The topical compositions of the subject mvention, mcludmg but not limited to lotions and creams, may compnse a dermatologically acceptable emollient Such compositions preferably contam from about 2% to about 50% of the emollient As used herein, "emollient" refers to a matenal useful for the prevention or relief of dryness, as well as for the protection of the skm A wide vanety of suitable emollients are known and may be used herem. Sagarin, Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp 32-43 (1972), incorporated herem by reference, contams numerous examples of matenals suitable as an emollient A prefeπed emollient is glycerin Glycerm is preferably used m an amount of from or about 0.001 to or about 20%, more preferably from or about 0 01 to or about 10%, most preferably from or about 0.1 to or about 5%, e.g., 3%

Lotions and creams accordmg to the present invention generally compnse a solution earner system and one or more emollients Lotions typically compnse from about 1% to about 20%, preferably from about 5% to about 10%, of emollient, from about 50% to about 90%, preferably from about 60% to about 80%, water; and farnesol in the above descnbed amounts A cream typically compnses from about 5% to about 50%), preferably from about 10% to about 20%, of emollient, from about 45% to about 85%, preferably from about 50%> to about 75%, water; and the farnesol m the above descnbed amounts.

Ointments of the present mvention may compnse a simple carner base of animal or vegetable oils or semi-solid hydrocarbons (oleagmous); absorption ointment bases which absorb water to form emulsions, or water soluble earners, e.g., a water soluble solution earner Ointments may further compnse a thickening agent, such as described m Sagarin, Cosmetics, Science and Technology, 2nd Edition, Vol 1, pp 72-73 (1972), incorporated herem by reference, and/or an emollient For example, an ointment may compnse from about 2% to about 10% of an emollient, from about 0 1% to about 2%> of a thickening agent, and farnesol m the above descnbed amount

Compositions of this mvention useful for cleansing ("cleansers") are formulated with a suitable earner, e.g., as descnbed above, and preferably contam, m addition to the oxnne compound m the above descnbed amounts, from about 1% to about 90%, more preferably from about 5% to about 10%, of a dermatologically acceptable surfactant The surfactant is suitably selected from amomc, nonionic, zwittenomc, amphotenc and ampholytic surfactants, as well as mixtures of these surfactants Such surfactants are well known to those skilled m the detergency art Nonlumtmg examples of possible surfactants mclude ιsoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, and sodium lauryl sulfate. See U.S. Patent No. 4,800,197, to Kowcz et al., issued January 24, 1989, which is incorporated herem by reference m its entirety, for exemplary surfactants useful herem. Examples of a broad vanety of additional surfactants useful herem are descnbed m McCutcheon's Detergents and

Emulsifiers, North Amencan Edition (1986), published by Allured Publishing Corporation. The cleansing compositions can optionally contam, at then- art-established levels, other matenals which are conventionally used m cleansing compositions. The physical form of the cleansmg compositions is not cntical The compositions can be, for example, formulated as toilet bars, liquids, shampoos, bath gels, hair conditioners, hair tomes, pastes, or mousses. Toilet bars are most prefeπed smce this is the form of cleansmg agent most commonly used to wash the skm Rinse-off cleansmg compositions, such as shampoos, require a delivery system adequate to deposit sufficient levels of actives on the skm and scalp A prefeπed delivery system mvolves the use of insoluble complexes For a more complete disclosure of such delivery systems, see U.S. Patent 4,835,148, Barford et al., issued May 30, 1989.

As used herem, the term "foundation" refers to a liquid, semi-liquid, semi-solid, or solid skm cosmetic which includes, but is not limited to lotions, creams, gels, pastes, cakes, and the like Typically the foundation is used over a large area of the skm, such as over the face, to provide a particular look. Foundations are typically used to provide an adherent base for color cosmetics such as rouge, blusher, powder and the like, and tend to hide skm imperfections and impart a smooth, even appearance to the skm Foundations of the present invention mclude a dermatologically acceptable carner for the farnesol and may mclude conventional ingredients such as oils, colorants, pigments, emollients, fragrances, waxes, stabilizers, and the like Exemplary earners and such other ingredients which are suitable for use herem are descnbed, for example, m copendmg patent application Serial No. 08/430,961, filed on April 28, 1995 m the names of Marcia L Canter, Bram D Barford, and Brian D. Hofπchter, and U.K. Patent Application GB 2274585-A, published on Jan. 23, 1993. Optional Components

The compositions of the present invention may contam a variety of other ingredients such as are conventionally used m a given product type provided that they do not unacceptably alter the benefits of the mvention.

In a prefeπed embodiment, where the composition is to be in contact with mammalian keratinous tissue, the optional components should be suitable for application to mammalian keratmous tissue, that is, when incorporated mto the composition they are suitable for use m contact with mammalian keratmous tissue, especially that of humans, without undue toxicity, incompatibility, instability, allergic response, and the like within the scope of sound medical judgment. The CTFA Cosmetic Ingredient Handbook, Second

Edition (1992) describes a wide vanety of nonlumtmg cosmetic and pharmaceutical ingredients commonly used m the skm care industry, which are suitable for use m the compositions of the present mvention

Examples of these ingredient classes mclude: abrasives, absorbents, aesthetic components such as fragrances, pigments, colorings/colorants, essential oils, skm sensates, astringents, etc. (e g., clove oil, menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazel distillate), anti-acne agents, anti- caking agents, antifoaming agents, antimicrobial agents (e g , lodopropyl butylcarbamate), antioxidants, bmders, biological additives, buffering agents, bulking agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents, external analgesics, film formers or matenals, e.g., polymers, for aidmg the film-forming properties and substantivity of the composition (e.g., copolymer of eicosene and vmyl pyπohdone), opacifying agents, pH adjusters, propellants, reducmg agents, sequestrants, skm bleaching and lightemng agents (e.g., hydroqumone, kojic acid, ascorbic acid, magnesium ascorbyl phosphate, ascorbyl glucosarmne), skin-conditioning agents (e.g , humectants, mcludmg miscellaneous and occlusive), skm soothmg and/or healmg agents (e.g., panthenol and denvatives (e.g , ethyl panthenol), aloe vera, pantothenic acid and its denvatives, allantom, bisabolol, and dipotassium glycynhizmate), skm treating agents, thickeners, and vitamins and denvatives thereof

In any embodiment of the present mvention, however, the actives useful herem can be categorized by the benefit they provide or by then postulated mode of action However, it is to be understood that the actives useful herem can m some mstances provide more than one benefit or operate via more than one mode of action Therefore, classifications herem are made for the sake of convemence and are not mtended to limit the active to that particular application or applications listed

Desquamation Actives

A safe and effective amount of a desquamation active may be added to the compositions of the present mvention, more preferably from about 0.1%) to about 10%, even more preferably from about 0 2% to about 5%, also preferably from about 0.5% to about 4%, by weight of the composition Desquamation actives enhance the skm appearance benefits of the present mvention For example, the desquamation actives tend to improve the texture of the skm (e.g , smoothness) One desquamation system that is suitable for use herem comprises sulfhydryl compounds and zwittenomc surfactants and is descnbed m copendmg application Senal No 08/480,632, filed on June 7, 1995 m the name of Donald L. Bissett, coπespondmg to PCT Application No. U.S. 95/08136, filed 6/29/95 Another desquamation system that is suitable for use herem compnses salicylic acid and zwittenomc surfactants and is described in copendmg patent application Senal No 08/554,944, filed on November 13, 1995 as a continuation of Senal No. 08/209,401, filed on March 9, 1994 m the name of Bissett, coπespondmg to PCT Application No 94/12745, filed 11/4/94, published 5/18/95. Zwittenomc surfactants such as descnbed m these applications are also useful as desquamatory agents herem, with cetyl betame bemg particularly prefeπed

Anti-Acne Actives

The compositions of the present mvention may compnse a safe and effective amount of one or more anti-acne actives. Examples of useful anti-acne actives mclude resorcmol, sulfur, salicylic acid, erythromycin, zmc, etc Further examples of suitable anti-acne actives are descnbed m further detail m U. S. Patent No. 5,607,980, issued to McAtee et al, on March 4, 1997.

Anti- Wrinkle Actives/ Anti-Atrophy Actives The compositions of the present mvention may further compnse a safe and effective amount of one or more anti-wnnkle actives or anti-atrophy actives Exemplary anti-wnnkle/anti-atrophy actives suitable for use m the compositions of the present mvention mclude sulfur-containing D and L ammo acids and their denvatives and salts, particularly the N-acetyl denvatives, a preferred example of which is N-acetyl-L- cysteme; thiols, e.g. ethane thiol; hydroxy acids (e.g., glycohc acid, lactic acid, and the like), phytic acid, lipoic acid; lysophosphatidic acid, skm peel agents (e g., phenol and the like), vitamin B3 compounds and retmoids which enhance the keratmous tissue appearance benefits of the present mvention, especially in regulating keratmous tissue condition, e.g., skm condition. a) Vitamm B3 Compounds

The compositions of the present mvention may compnse a safe and effective amount of a vitamm B3 compound. Vitamm B3 compounds are particularly useful for regulating skm condition as descnbed m co-pendmg U S. Application Senal No 08/834,010, filed Apnl 11, 1997 (coπespondmg to international publication WO 97/39733 Al, published October 30, 1997). When vitamm B3 compounds are present m the compositions of the mstant mvention, the compositions preferably comprise from about 0.01% to about 50%, more preferably from about 0.1% to about 10%, even more preferably from about 0.5% to about 10%>, and still more preferably from about 1% to about 5%>, most preferably from about 2% to about 5%, by weight of the composition, of the vitamm B3 compound

As used herem, "vitamm B3 compound" means a compound havmg the formula

wherem R is - CONH2 (i.e , niacinamide), - COOH (I e., nicotimc acid) or - CH20H (l e , nicotinyl alcohol); derivatives thereof; and salts of any of the foregomg

Exemplary derivatives of the foregomg vitamm B3 compounds mclude nicotimc acid esters, mcludmg non-vasodilatmg esters of nicotmic acid (e g., tocopheryl mcotmate), nicotinyl ammo acids, mcotmyl alcohol esters of carboxylic acids, nicotimc acid N-oxide and niacinamide N-oxide

Examples of suitable vitamm B3 compounds are well known m the art and are commercially available from a number of sources, e g., the Sigma Chemical Company (St Louis, MO), ICN Biomedicals, Inc. (Irvin, CA) and Aldnch Chemical Company (Milwaukee, WI)

The vitamm compounds may be mcluded as the substantially pure matenal, or as an extract obtained by suitable physical and or chemical isolation from natural (e.g , plant) sources

Prefened vitamin B3 compounds are niacinamide, tocopherol mcotmate, and mixtures thereof b) Retmoids

The compositions of the present mvention may also compnse a retinoid. As used herem, "retinoid" mcludes all natural and/or synthetic analogs of Vitamin A or retinol-hke compounds which possess the biological activity of Vitamin A m the skm as well as the geometric isomers and stereoisomers of these compounds. The retinoid is preferably retinol, retmol esters (e g., C2 - C22 alkyl esters of retmol, mcludmg retinyl palmitate, rehnyl acetate, retmyl propionate), retinal, and/or rettnoic acid (mcludmg all-trans retmoic acid and/or 13-cιs-retιnoιc acid), more preferably retmoids other than retmoic acid These compounds are well known m the art and are commercially available from a number of sources, e.g., Sigma Chemical Company (St. Louis, MO), and Boerhinger Mannheim (Indianapolis, IN). Other retmoids which are useful herem are descnbed in U.S Patent Nos. 4,677,120, issued Jun 30, 1987 to Pansh et al ; 4,885,311, issued Dec. 5, 1989 to Parish et al., 5,049,584, issued Sep. 17, 1991 to Purcell et al , 5,124,356, issued Jun. 23, 1992 to Purcell et al.; and Reissue 34,075, issued Sep. 22, 1992 to Purcell et al Other suitable retmoids are tocopheryl-retinoate [tocopherol ester of retmoic acid (trans- or cis-), adapalene {6-[3-(l-adamantyι)-4- methoxyphenyl]-2-naphthoιc acid}, and tazarotene (ethyl 6-[2-(4,4-dimethylfhiochroman-6-yl)- ethynyljmcotmate) Prefeπed retmoids are retmol, retmyl palmitate, retmyl acetate, retmyl propionate, retmal and combinations thereof.

The retmoid may be mcluded as the substantially pure matenal, or as an extract obtamed by suitable physical and or chemical isolation from natural (e g , plant) sources The retmoid is preferably substantially pure, more preferably essentially pure.

The compositions of this mvention may contam a safe and effective amount of the retinoid, such that the resultant composition is safe and effective for regulatmg keratmous tissue condition, preferably for regulatmg visible and/or tactile discontinuities m skm, more preferably for regulatmg signs of skm agmg, even more preferably for regulatmg visible and/or tactile discontinuities m skm texture associated with skm agmg The compositions preferably contam from or about 0 005% to or about 2%, more preferably 0 01% to or about 2%, retmoid Retmol is most preferably used m an amount of from or about 0.01% to or about 0.15%, retmol esters are most preferably used m an amount of from or about 0.01% to or about 2% (e g., about 1%); retmoic acids are most preferably used m an amount of from or about 0.01% to or about 0.25%, tocopheryl-retinoate, adapalene, and tazarotene are most preferably used m an amount of from or about 0.01% to or about 2%

Where the compositions of the present mvention contam both a retmoid and a Vitamin B3 compound, the retmoid is preferably used m the above amounts, and the vitamm B3 compound is preferably used m an amount of from or about 0 1% to or about 10%, more preferably from or about 2% to or about 5%

Anti-Oxidants/Radical Scavengers

The compositions of the present mvention may mclude a safe and effective amount of an anti- oxidant/radical scavenger. The anti-oxidant/radical scavenger is especially useful for providmg protection agamst UV radiation which can cause mcreased scalmg or texture changes m the stratum corneum and against other envnonmental agents which can cause skm damage.

A safe and effective amount of an anti-oxidant/radical scavenger may be added to the compositions of the subject mvention, preferably from about 0.1% to about 10%, more preferably from about 1% to about 5%, of the composition

Anti-oxidants/radical scavengers such as ascorbic acid (vitamin C) and its salts, ascorbyl esters of fatty acids, ascorbic acid denvatives (e.g , magnesium ascorbyl phosphate), tocopherol (vitamm E), tocopherol sorbate, tocopherol acetate, other esters of tocopherol, butylated hydroxy benzoic acids and then salts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxyhc acid (commercially available under the tradename TroloxR), gallic acid and its alkyl esters, especially propyl gallate, unc acid and its salts and alkyl esters, sorbic acid and its salts, hpoic acid, amines (e.g., N,N-dιethylhydroxylamme, amino-guanidine), sulfhydryl compounds (e.g., glutathione), dihydroxy fumaπc acid and its salts, lycme pidolate, arginme pilolate, nordihydroguaiaretic acid, bioflavonoids, lysme, methionme, prolme, superoxide dismutase, silymann, tea extracts, grape skin/seed extracts, melamn, and rosemary extracts may be used Preferred anti- oxidants/radical scavengers are selected from tocopherol sorbate and other esters of tocopherol, more preferably tocopherol sorbate For example, the use of tocopherol sorbate m topical compositions and applicable to the present mvention is descnbed m U.S Patent No 4,847,071, issued on July 11, 1989 to Donald L Bissett, Rodney D. Bush and Ranjit Chatterjee

Chelators

The compositions of the present mvention may also compnse a safe and effective amount of a chelator or chelatmg agent As used herem, "chelator" or "chelatmg agent" means an active agent capable of removmg a metal ion from a system by forming a complex so that the metal ion cannot readily participate m or catalyze chemical reactions The inclusion of a chelatmg agent is especially useful for providmg protection agamst UV radiation which can contribute to excessive scalmg or skm texture changes and agamst other envnonmental agents which can cause skm damage

A safe and effective amount of a chelatmg agent may be added to the compositions of the subject mvention, preferably from about 0.1% to about 10%, more preferably from about 1%> to about 5%, of the composition. Exemplary chelators that are useful herem are disclosed m International Publication No 91/16035, Bush et al., published 10/31/95, and International Publication No 91/16034, Bush et al , published 10/31/95. Flavonoids

The compositions of the present mvention may optionally compnse a flavonoid compound Flavonoids are broadly disclosed m U S Patents 5,686,082 and 5,686,367, both of which are herem incorporated by reference Flavonoids suitable for use m the present mvention are flavanones selected from the group consistmg of unsubstituted flavanones, mono-substituted flavanones, and mixtures thereof; chalcones selected from the group consistmg of unsubstituted chalcones, mono-substituted chalcones, di- substituted chalcones, tn-substituted chalcones, and mixtures thereof; flavones selected from the group consistmg of unsubstituted flavones, mono-substituted flavones, di-substituted flavones, and mixtures thereof; one or more isoflavones; coumanns selected from the group consistmg of unsubstituted coumanns, mono-substituted coumanns, di-substituted coumanns, and mixtures thereof, chromones selected from the group consisting of unsubstituted chromones, mono-substituted chromones, di-substituted chromones, and mixtures thereof; one or more dicoumarols, one or more chromanones, one or more chromanols; isomers (e.g., cis/trans isomers) thereof; and mixtures thereof. By the term "substituted" as used herem means flavonoids wherem one or more hydrogen atom of the flavonoid has been mdependently replaced with hydroxyl, C1-C8 alkyl, C1-C4 alkoxyl, O-glycoside, and the like or a mixture of these substituents.

Examples of suitable flavonoids mclude, but are not limited to, unsubstituted flavonone, mono- hydroxy flavanones (e.g., 2'-hydroxy flavanone, 6-hydroxy flavanone, 7-hydroxy flavanone, etc.), mono- alkoxy flavanones (e.g., 5-methoxy flavanone, 6-methoxy flavanone, 7-methoxy flavanone, 4'-methoxy flavanone, etc ), unsubstituted chalcone (especially unsubstituted trans-chalcone), mono-hydroxy chalcones (e g , 2'-hydroxy chalcone, 4'-hydroxy chalcone, etc ), di-hydroxy chalcones (e g , 2',4-dihydroxy chalcone, 2',4'-dιhydroxy chalcone, 2,2 '-dihydroxy chalcone, 2',3-dιhydroxy chalcone, 2 ',5 '-dihydroxy chalcone, etc ), and tn-hydroxy chalcones (e g , 2',3',4'-tnhydroxy chalcone, 4,2',4'-tπhydroxy chalcone, 2,2',4'- tnhydroxy chalcone, etc ), unsubstituted flavone, 7,2'-dιhydroxy flavone, 3',4'-dιhydroxy naphthoflavone, 4'- hydroxy flavone, 5,6-benzoflavone, and 7,8-benzoflavone, unsubstituted isoflavone, daidzem (7,4'- dmydroxy isoflavone), 5,7-dιhydroxy-4'-methoxy isoflavone, soy isoflavones (a mixture extracted from soy), unsubstituted coumann, 4-hydroxy coumann, 7-hydroxy coumarm, 6-hydroxy-4-methyl coumann, unsubstituted chromone, 3-formyl chromone, 3-formyl-6-ιsopropyl chromone, unsubstituted dicoumarol, unsubstituted chromanone, unsubstituted chromanol, and mixtures thereof

Prefeπed for use herem are uiisubstituted flavanone, methoxy flavanones, unsubstituted chalcone, 2',4-dihydroxy chalcone, and mixtures thereof Most prefeπed are unsubstituted flavanone, unsubstituted chalcone (especially the trans isomer), and mixtures thereof

They can be synthetic matenals or obtained as extracts from natural sources (e g , plants) The naturally sourced matenal can also further be denvatized (e g , an ester or ether denvative prepared following extraction from a natural source) Flavonoid compounds useful herem are commercially available from a number of sources, e g , Indofine Chemical Company, Inc (Somerville, New Jersey), Steraloids, Inc (Wilton, New Hampshire), and Aldnch Chemical Company, Inc (Milwaukee, Wisconsin)

Mixtures of the above flavonoid compounds may also be used

The herem descnbed flavonoid compounds are preferably present m the mstant mvention at concentrations of from about 0 01% to about 20%, more preferably from about 0 1% to about 10% and most preferably from about 0 5% to about 5%

Anti-Inflammatory Agents

A safe and effective amount of an anti-mflammatory agent may be added to the compositions of the present mvention, preferably from about 0 1% to about 10%, more preferably from about 0 5% to about 5%, of the composition The anti-inflammatory agent enhances the skm appearance benefits of the present mvention, e g , such agents contnbute to a more uniform and acceptable skm tone or color The exact amount of anti-mflammatory agent to be used m the compositions will depend on the particular anti- lnflammatory agent utilized smce such agents vary widely m potency

Steroidal anfr-niflamrnatory agents, mcludmg but not limited to, corticosteroids such as hydrocortisone, hydroxyltnamcmolone, alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethasone dipropionates, clobetasol valerate, desomde, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlonsone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosmolone acetomde, fluocinonide, flucorhne butylesters, fluocortolone, fluprednidene (fluprednyhdene) acetate, flurandrenolone, halcmomde, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, tnamcinolone acetomde, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone, fludrocortisone, diflurosone diacetate, fluradrenolone acetomde, medrysone, amcmafel, amcmafide, betamethasone and the balance of its esters, chloropredmsone, chlorpredmsone acetate, clocortelone, clescmolone, dichlonsone, diflurprednate, flucloromde, flumsolide, fluoromethalone, fluperolone, flupredmsolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortamate, meprednisone, paramethasone, prednisolone, predmsone, beclomethasone dipropionate, tnamcinolone, and mixtures thereof may be used The prefeπed steroidal anti-inflammatory for use is hydrocortisone

A second class of anti-mflammatory agents which is useful m the compositions mcludes the nonsteroidal anti-mflammatory agents The vanety of compounds encompassed by this group are well- known to those skilled m the art For detailed disclosure of the chemical structure, synthesis, side effects, etc of non-steroidal anti-mflammatory agents, one may refer to standard texts, mcludmg Anti-mflammatory and Anti-Rheumatic Drugs, K D Rainsford, Vol I-III, CRC Press, Boca Raton, (1985), and Anti- iriflamrnatory Agents, Chemistry and Pharmacology, 1, R A Scheπer, et al , Academic Press, New York (1974)

Specific non-steroidal anti-mflammatory agents useful m the composition mvention include, but are not limited to

1) the oxicams, such as pnoxicam, lsoxicam, tenoxicam, sudoxicam, and CP-14,304,

2) the sahcylates, such as aspirin, disalcid, benorylate, tnhsate, safapryn, solpnn, diflunisal, and fendosal,

3) the acetic acid denvatives, such as diclofenac, fenclofenac, lndomethacm, sulmdac, tolmetm, isoxepac, furofenac, tiopmac, zidometacm, acematacin, fentiazac, zomepnac, clmdanac, oxepmac, felbmac, and ketorolac,

4) the fenamates, such as mefenamic, meclofenamic, flufenamic, mflumic, and tolfenamic acids,

5) the propiomc acid denvatives, such as lbuprofen, naproxen, benoxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufen, indopropfen, pirprofen, carprofen, oxaprozm, pranoprofen, miroprofen, tioxaprofen, suprofen, almmoprofen, and tiaprofenic, and

6) the pyrazoles, such as phenylbutazone, oxyphenbutazone, feprazone, azapropazone, and tnmethazone

Mixtures of these non-steroidal ann-inflammatory agents may also be employed, as well as the dermatologically acceptable salts and esters of these agents For example, etofenamate, a flufenamic acid denvative, is particularly useful for topical application Of the nonsteroidal anti-mflammatory agents, lbuprofen, naproxen, flufenamic acid, etofenamate, aspinn, mefenamic acid, meclofenamic acid, pnoxicam and felbmac are prefeπed, lbuprofen, naproxen, ketoprofen, etofenamate, aspirin and flufenamic acid are most preferred

Finally, so-called "natural" anti-inflammatory agents are useful m methods of the present mvention

Such agents may suitably be obtained as an extract by suitable physical and/or chemical isolation from natural sources (e g , plants, fungi, by-products of microorganisms) For example, candehlla wax, alpha bisabolol, aloe vera, Manjistha (extracted from plants m the genus Rubia, particularly Rubia Cordifolia), and Guggal (extracted from plants m the genus Commiphora, particularly Commiphora Mukul), kola extract, chamomile, and sea whip extract, may be used

Additional anti-mflammatory agents useful herem include compounds of the Liconce (the plant genus/species Glycyπhiza glabra) family, mcludmg glycyπhetic acid, glycyrrhrzic acid, and denvatives thereof (e g , salts and esters) Suitable salts of the foregomg compounds mclude metal and ammomum salts Suitable esters mclude C2 - C24 saturated or unsaturated esters of the acids, preferably CIO - C24, more preferably C16 - C24 Specific examples of the foregomg mclude oil soluble liconce extract, the glycynhizic and glycyπhetic acids themselves, monoammonium glycyπhizinate, monopotassium glycyrthizinate, dipotassium glycyπhizinate, 1-beta-glycynhetιc acid, stearyl glycyπhehnate, and 3- stearyloxy-glycyπhetinic acid, and disodium 3-succιnyloxy-beta-glycyπhetιnate Stearyl glycynhetmate is prefened

Anti-Celluhte Agents

The compositions of the present mvention may also compnse a safe and effective amount of an anti-celluhte agent Suitable agents may mclude, but are not limited to, xanfhine compounds (e g , caffeme, theophylhne, fheobromine, and aminophylhne)

Topical Anesthetics

The compositions of the present mvention may also comprise a safe and effective amount of a topical anesthetic Examples of topical anesthetic drugs mclude benzocaine, hdocaine, bupivacame, chlorprocame, dibucame, etidocame, mepivacame, tetracaine, dyclonine, hexylcame, procaine, ***e, ketamine, pramoxme, phenol, and pharmaceutically acceptable salts thereof

Tanning Actives

The compositions of the present mvention may compnse a tanning active When present, it is preferable that the compositions compnse from about 0 1% to about 20%, more preferably from about 2% to about 7%, and most preferably from about 3% to about 6%, by weight of the composition, of dihydroxyacetone as an artificial tanning active

Dihydroxyacetone, which is also known as DHA or l,3-dιhydroxy-2-propanone, is a white to off- white, crystalline powder This matenal can be represented by the chemical formula C3H603 and the following chemical structure

O

HOH₂C— C -CH₂OH

The compound can exist as a mixture of monomers and dimers, with the dimers predominating m the solid crystalline state Upon heatmg or melting, the dimers break down to yield the monomers This conversion of the dimenc form to the monomenc form also occurs in aqueous solution Dihydroxyacetone is also known to be more stable at acidic pH values See The Merck Index, Tenth Edition, entry 3167, p 463 (1983), and "Dihydroxyacetone for Cosmetics", E Merck Technical Bulletin, 03-304 110, 319 897, 180 588.

Skm Lightemng Agents

The compositions of the present mvention may compnse an additional skm lightemng agent When used, the compositions preferably comprise from about 0.1% to about 10%, more preferably from about 0.2% to about 5%, also preferably from about 0.5% to about 2%, by weight of the composition, of a skm lightemng agent. Suitable skm lightemng agents mclude those known m the art, mcludmg kojic acid, arbutm, macmaimde, ascorbic acid and denvatives thereof, e g , magnesium ascorbyl phosphate or sodium ascorbyl phosphate. Skm lightemng agents suitable for use herein also mclude those descnbed m copendmg patent application Senal No 08/479,935, filed on June 7, 1995 in the name of Hillebrand, coπespondmg to PCT Application No U.S 95/07432, filed 6/12/95; and copendmg patent application Senal No. 08/390,152, filed on February 24, 1995 m the names of Kalla L Kvalnes, Mitchell A DeLong, Barton J Bradbury, Curtis B. Motley, and John D Carter, coπespondmg to PCT Application No U.S 95/02809, filed 3/1/95, published 9/8/95

Antimicrobial and Antifungal Actives

The compositions of the present mvention may compnse an antimicrobial or antifungal active Such actives are capable of destroying microbes, preventmg the development of microbes or preventing the pathogenic action of microbes. A safe and effective amount of an antimicrobial or antifungal active may be added to the present compositions, preferably, from about 0 001% to about 10%, more preferably from about 0.01%) to about 5%>, and most preferably from about 0 05% to about 2%>.

Examples of antimicrobial and antifungal actives mclude β-lactam drugs, qumolone drugs, ciprofloxacin, norfloxacin, tetracychne, eryfhromycm, amikacm, 2,4,4'-tnchloro-2'-hydroxy diphenyl ether, 3,4,4'-tπchlorobamlιde, phenoxyethanol, phenoxy propanol, phenoxyisopropanol, doxycychne, capreomycm, chlorhexidine, chlortetracychne, oxytetracychne, clmdamycm, ethambutol, hexamidine lsethionate, metronidazole, pentamidine, gentamicin, kanamycin, lmeomycm, methacychne, methenamine, minocychne, neomycin, netilmicin, paromomycm, streptomycin, tobramycm, miconazole, tetracycline hydrochlonde, eryfhromycm, zinc erythromycm, erythromycm estolate, erythromycm stearate, amikacm sulfate, doxycyclme hydrochlonde, capreomycm sulfate, chlorhexidine gluconate, chlorhexidine hydrochlonde, chlortetracycline hydrochlonde, oxytetracychne hydrochlonde, clmdamycm hydrochlonde, ethambutol hydrochlonde, metronidazole hydrochlonde, pentamidine hydrochlonde, gentamicin sulfate, kanamycm sulfate, lmeomycm hydrochlonde, methacychne hydrochlonde, methenamine hippurate, methenamine mandelate, minocycline hydrochlonde, neomycm sulfate, netilmicin sulfate, paromomycm sulfate, streptomycin sulfate, tobramycm sulfate, miconazole hydrochlonde, ketaconazole, amanfadine hydrochlonde, amanfadine sulfate, octopirox, parachlorometa xylenol, nystatm, tolnaftate, zmc pyπthione and clotnmazole.

Preferred examples of actives useful herem mclude those selected from the group consistmg of salicylic acid, benzoyl peroxide, 3-hydroxy benzoic acid, glycohc acid, lactic acid, 4-hydroxy benzoic acid, acetyl salicylic acid, 2-hydroxybutanoιc acid, 2-hydroxypentanoιc acid, 2-hydroxyhexanoic acid, cis-retmoic acid, trans-retmoic acid, retmol, phytic acid, N-acetyl-L-cysteme, hpoic acid, azelaic acid, arachidonic acid, benzoylperoxide, tetracyclme, lbuprofen, naproxen, hydrocortisone, acetommophen, resorcmol, phenoxyefhanol, phenoxypropanol, phenoxyisopropanol, 2,4,4'-tnchloro-2'-hydroxy diphenyl ether, 3,4,4'- tπchlorocarbamlide, octopirox, lidocame hydrochlonde, clotnmazole, miconazole, ketoconazole, neocycm sulfate, and mixtures thereof.

Sunscreen Actives

Exposure to ultraviolet light can result m excessive scalmg and texture changes of the stratum corneum. Therefore, the compositions of the subject mvention may optionally contam a sunscreen active As used herem, "sunscreen active" mcludes both sunscreen agents and physical sunblocks. Suitable sunscreen actives may be orgamc or morgamc.

A wide variety of conventional sunscreen actives are suitable for use herem. Sagarin, et al , at Chapter VIII, pages 189 et seq., of Cosmetics Science and Technology (1972), discloses numerous suitable actives Specific suitable sunscreen actives mclude, for example p-aminobenzoic acid, its salts and its denvatives (ethyl, isobutyl, glyceryl esters, p-dunethylammobenzoic acid), anthranilates (i.e., o-amino- benzoates, methyl, menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl, and cyclohexenyl esters), sahcylates (amyl, phenyl, octyl, benzyl, menthyl, glyceryl, and di-pro-pyleneglycol esters); cinnamic acid denvatives (menthyl and benzyl esters, a-phenyl cmnamomtnle, butyl cinnamoyl pyruvate), dihydroxycinnamic acid derivatives (umbelhferone, methylumbelhferone, methylaceto-umbelliferone), tnhydroxy-cinnamic acid denvatives (esculetm, methylesculetm, daphnetin, and the glucosides, esculm and daphnin); hydrocarbons (diphenylbutadiene, stilbene), dibenzalacetone and benzalacetophenone, naphtholsulfonates (sodium salts of 2-naphthol-3,6-dιsulfonιc and of 2-naphfhol-6,8-dιsulfomc acids); di- hydroxynaphthoic acid and its salts, o- and p-hydroxybiphenyldisulfonates, coumann denvatives (7- hydroxy, 7-methyl, 3-phenyl), diazoles (2-acetyl-3-bromoιndazole, phenyl benzoxazole, methyl naphthoxazole, vanous aryl benzothiazoles); qumme salts (bisulfate, sulfate, chlonde, oleate, and tannate), qumolme denvatives (8-hydroxyqumolme salts, 2-phenylquιnolιne), hydroxy- or mefhoxy-subsntuted benzophenones; unc and violunc acids; tanmc acid and its derivatives (e g , hexaethylether), (butyl carbotol) (6-propyl piperonyl) ether; hydroqumone; benzophenones (oxybenzene, suhsobenzone, dioxybenzone, benzoresorcmol, 2,2',4,4'-tetrahydroxybenzophenone, 2,2'-dιhydroxy-4,4'- dnnethoxybenzophenone, octabenzone, 4-ιsopropyldιbenzoylmethane, butylmethoxydibenzoylmethane, etocrylene; octocrylene, [3-(4'-methylbenzyhdene bornan-2-one) and 4-ιsopropyl-dι-benzoylmethane.

Of these, 2-ethylhexyl-p-methoxycinnamate (commercially available as PARSOL MCX), 4,4'-t- butyl methoxydibenzoyl-methane (commercially available as PARSOL 1789), 2-hydroxy-4- methoxybenzophenone, octyldunethyl-p-aπunobenzoic acid, digalloyltπoleate, 2,2-dιhydroxy-4- methoxybenzophenone, ethyl-4-(bιs(hydroxy-propyl))ammobenzoate, 2-ethylhexyl-2-cyano-3,3- diphenylacrylate, 2-ethylhexyl-sahcylate, glyceryl-p-ammobenzoate, 3,3,5-tn-methylcyclohexylsalιcylate, mefhylanthranilate, p-dunethyl-am obenzoic acid or ammobenzoate, 2-ethylhexyl-p-dmιethyl-ammo- benzoate, 2-phenylbeιιzιmιdazole-5-sulfonιc acid, 2-(p-dnnethylaπnnophenyl)-5-sulfomcbenzoxazoιc acid, octocrylene and mixtures of these compounds, are prefened

More prefened orgamc sunscreen actives useful m the compositions useful m the subject mvention are 2-ethylhexyl-p-methoxycinnamate, butylmethoxydibenzoyl-mefhane, 2-hydroxy-4-methoxybenzo- phenone, 2-phenylbenzιmιdazole-5-sulfonιc acid, octyldimethyl-p-ammobenzoic acid, octocrylene and mixtures thereof.

Also particularly useful m the compositions are sunscreen actives such as those disclosed m U.S Patent No 4,937,370 issued to Sabatelh on June 26, 1990, and U S Patent No 4,999,186 issued to Sabatelh & Spirnak on March 12, 1991 The sunscreening agents disclosed therein have, m a smgle molecule, two distmct chromophore moieties which exhibit different ultra-violet radiation absorption spectra One of the chromophore moieties absorbs predominantly m the UVB radiation range and the other absorbs strongly m the UVA radiation range.

Prefened members of this class of sunscreening agents are 4-N,N-(2-ethylhexyl)methyl- aminobenzoic acid ester of 2,4-dιhydroxybenzophenone, N,N-dι-(2-ethylhexyl)-4-amιnobenzoιc acid ester with 4-hydroxydιbenzoylmefhane; 4-N,N-(2-ethylhexyl)methyl-amιnobenzoιc acid ester with 4- hydroxydibenzoylmethane; 4-N,N-(2-ethylhexyl)mefhyl-ammobenzoic acid ester of 2-hydroxy-4-(2- hydroxyethoxy)benzophenone; 4-N,N-(2-ethylhexyl)-mefhylammobenzoιc acid ester of 4-(2- hydroxyethoxy)dιbenzoylmethane, N,N-dι-(2-ethylhexyl)-4-ammobenzoιc acid ester of 2-hydroxy-4-(2- hydroxyethoxy)benzophenone; and N,N-dι-(2-ethylhexyl)-4-ammobenzoιc acid ester of 4-(2- hydroxyethoxy)dιbenzoylmethane, zmc oxide, titanium oxide, and mixtures thereof

Especially prefeπed sunscreen actives mclude 4,4'-t-butylmethoxydιbenzoylmefhane, 2-ethylhexyl- p-methoxycinnamate, phenyl benzunidazole sulfomc acid, zmc oxide, titanium dioxide, octocrylene, and combinations thereof

A safe and effective amount of the sunscreen active is used, typically from about 1% to about 20%, more typically from about 2%> to about 10% by weight of the composition Exact amounts will vary dependmg upon the sunscreen chosen and the desned Sun Protection Factor (SPF).

Conditioning Agents

The compositions of the present mvention may compnse a conditioning agent selected from the group consisting of humectants, moisturizers, or skm conditioners A vanety of these matenals can be employed and each can be present at a level of from about 0.01% to about 20%>, more preferably from about

0.1% to about 10%, and most preferably from about 0.5% to about 7% by weight of the composition These matenals mclude, but are not limited to, guamdme; urea, glycohc acid and glycolate salts (e.g ammomum and quaternary alkyl ammomum); salicylic acid; lactic acid and lactate salts (e.g , ammomum and quaternary alkyl ammomum); aloe vera m any of its vanety of forms (e.g , aloe vera gel), polyhydroxy alcohols such as sorbitol, glycerol, hexanetnol, butanetnol, propylene glycol, butylene glycol, hexylene glycol and the like, polyethylene glycols; sugars (e.g., mehbiose) and starches; sugar and starch denvatives (e.g , alkoxylated glucose, fucose); hyaluronic acid, lactamide monoethanolamine; acetamide monoethanolamine; and mixtures thereof Also useful herem are the propoxylated glycerols descnbed ln U S Patent No 4,976,953, to On et al, issued December 11, 1990

Also useful are vanous C1-C30 monoesters and polyesters of sugars and related matenals These esters are derived from a sugar or polyol moiety and one or more carboxyhc acid moieties Such ester matenals are further described m, U S Patent No 2,831,854, U S Patent No 4,005,196, to Jandacek, issued January 25, 1977, U S Patent No 4,005,195, to Jandacek, issued January 25, 1977, U S Patent No 5,306,516, to Letton et al, issued Apnl 26, 1994, U S Patent No 5,306,515, to Letton et al, issued Apnl 26, 1994, U S Patent No 5,305,514, to Letton et al, issued Apnl 26, 1994, U S Patent No 4,797,300, to Jandacek et al, issued January 10, 1989, U S Patent No 3,963,699, to Rizzi et al, issued June 15, 1976, U S Patent No 4,518,772, to Volpenhein, issued May 21, 1985, and U S Patent No 4,517,360, to Volpenhein, issued May 21, 1985

Preferably, the conditioning agent is selected from the group consisting of glycerol, urea, guanidine, sucrose polyester, and combmations thereof

Thickening Agent (mcludmg thickeners and gelling agents)

The compositions of the present mvention can compnse one or more thickening agents, preferably from about 0 1% to about 5%, more preferably from about 0 1% to about 3%, and most preferably from about 0 25% to about 2%, by weight of the composition

Nonlimiting classes of thickening agents mclude those selected from the group consistmg of a) Carboxyhc Acid Polymers

These polymers are crosslinked compounds contammg one or more monomers derived from acrylic acid, substituted acrylic acids, and salts and esters of these acrylic acids and the substituted acrylic acids, wherem the crosslinking agent contams two or more carbon-carbon double bonds and is derived from a polyhydnc alcohol Polymers useful m the present invention are more fully descnbed in U S Patent No 5,087,445, to Haffey et al, issued February 11, 1992, U S Patent No 4,509,949, to Huang et al, issued Apnl 5, 1985, U S Patent No 2,798,053, to Brown, issued July 2, 1957, and m CTFA International Cosmetic Ingredient Dictionary, Fourth Edition, 1991, pp 12 and 80

Examples of commercially available carboxyhc acid polymers useful herem mclude the carbomers, which are homopolymers of acrylic acid crosslinked with allyl ethers of sucrose or pentaerytntol The carbomers are available as the Carbopol® 900 series from B F Goodnch (e g , Carbopol® 954) In addition, other suitable carboxyhc acid polymenc agents mclude copolymers of C 10-30 alkyl acrylates with one or more monomers of acrylic acid, methacryhc acid, or one of then short cham (I e , Cl-4 alcohol) esters, wherem the crosslinking agent is an allyl ether of sucrose or pentaerytntol These copolymers are known as acrylates/C 10-30 alkyl acrylate crosspolymers and are commercially available as Carbopol® 1342, Carbopol® 1382, Pemulen TR-1, and Pemulen TR-2, from B F Goodnch In other words, examples of carboxyhc acid polymer thickeners useful herem are those selected from the group consistmg of carbomers, acrylates/C 10-C30 alkyl acrylate crosspolymers, and mixtures thereof b) Crosslinked Polyacrylate Polymers

The compositions of the present mvention can optionally comprise crosslinked polyacrylate polymers useful as thickeners or gellmg agents mcludmg both catiomc and nomomc polymers, with the catiomcs bemg generally prefeπed Examples of useful crosslinked nomomc polyacrylate polymers and crosslinked catiomc polyacrylate polymers are those described m U S Patent No 5 100,660, to Hawe et al, issued March 31, 1992, U S Patent No 4,849,484, to Heard, issued July 18, 1989, U S Patent No 4,835,206, to Fanar et al, issued May 30, 1989, U S Patent No 4,628,078 to Glover et al issued December 9, 1986, U S Patent No 4,599,379 to Flesher et al issued July 8, 1986, and EP 228,868, to Fanar et al, published July 15, 1987 c) Polyacrylamide Polymers

The compositions of the present mvention can optionally comprise polyacrylamide polymers, especially nomomc polyacrylamide polymers mcludmg substituted branched or unbranched polymers Most prefeπed among these polyacrylamide polymers is the nomomc polymer given the CTFA designation polyacrylamide and isoparaffm and laureth-7, available under the Tradename Sepigel 305 from Seppic Corporation (Farrfield, NJ)

Other polyacrylamide polymers useful herein mclude multi-block copolymers of acrylamides and substituted acrylamides with acrylic acids and substituted acrylic acids Commercially available examples of these multi-block copolymers mclude Hypan SR150H, SS500V, SS500W, SSSA100H, from Lipo Chemicals, Inc , (Patterson, NJ) d) Polysacchandes

A wide variety of polysacchandes are useful herein "Polysacchandes" refer to gellmg agents which contam a backbone of repeatmg sugar (l e , carbohydrate) units Nonlimiting examples of polysacchaπde gellmg agents mclude those selected from the group consistmg of cellulose, carboxymethyl hydroxyefhylcellulose, cellulose acetate propionate carboxylate, hydroxyethylcellulose, hydroxyethyl ethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, methyl hydroxyethylcellulose, microcrystallme cellulose, sodium cellulose sulfate, and mixtures thereof Also useful herem are the alkyl substituted celluloses In these polymers, the hydroxy groups of the cellulose polymer is hydroxyalkylated (preferably hydroxyefhylated or hydroxypropylated) to form a hydroxyalkylated cellulose which is then further modified with a C10-C30 straight cham or branched cham alkyl group through an ether linkage Typically these polymers are ethers of C10-C30 straight or branched cham alcohols with hydroxyalkylcelluloses Examples of alkyl groups useful herem mclude those selected from the group consistmg of stearyl, isostearyl, lauryl, mynstyl, cetyl, lsocetyl, cocoyl (1 e alkyl groups denved from the alcohols of coconut oil), palmityl, oleyl, lmoleyl, linolenyl, ncmoleyl, behenyl, and mixtures thereof Prefeπed among the alkyl hydroxyalkyl cellulose ethers is the matenal given the CTFA designation cetyl hydroxyethylcellulose, which is the ether of cetyl alcohol and hydroxyethylcellulose This matenal is sold under the tradename Natrosol® CS Plus from Aqualon Corporation (Wilmington, DE) Other useful polysacchandes mclude scleroglucans compnsmg a linear cham of (1-3) linked glucose umts with a (1-6) linked glucose every three umts, a commercially available example of which is Clearogel™ CS11 from Michel Mercier Products Inc (Mountainside, NJ) e) Gums

Other thickening and gellmg agents useful herem mclude materials which are pnmanly denved from natural sources Nonlimiting examples of these gellmg agent gums mclude matenals selected from the group consisting of acacia, agar, algm, alginic acid, ammomum algmate, amylopectin, calcium algmate, calcium canageenan, carnitme, caπageenan, dextrin, gelatm, gellan gum, guar gum, guar hyάroxypropyltrimonium chlonde, hectoπte, hyaluroinic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp, locust bean gum, natto gum, potassium algmate, potassium caπageenan, propylene glycol algmate, sclerotium gum, sodium carboyxmethyl dextran, sodium canageenan, tragacanfh gum, xanthan gum, and mixtures thereof

Prefeπed compositions of the present mvention mclude a thickening agent selected from the group consistmg of carboxyhc acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers and mixtures thereof, more preferably selected from the group consistmg of carboxyhc acid polymers, polyacrylamide polymers, and mixtures thereof Preparation of Compositions

The compositions of the present invention are generally prepared by conventional methods such as are known m the art of making topical compositions Such methods typically mvolve mixing of the ingredients m one or more steps to a relatively uniform state, with or without heating, coolmg, application of vacuum, and the like Methods for Lighte ng Keratinous Tissue

The compositions of the present mvention are useful for lightemng keratinous tissue, preferably mammalian, and more preferably human keratmous tissue In an even more prefeπed embodiment, the compositions of the present invention are useful for lightemng human skm, more especially facial and hand skm The compositions are especially useful for lightemng hyperpigmented regions of skm The methods discussed herem may also be used to lighten keratmous tissues such as han , nails, etc

The method of lightemng keratmous tissue mvolves topically applymg to the keratmous tissue in need of treatment a safe and effective amount of a composition compnsmg a safe and effective amount of an oxnne compound and a dermatologically acceptable earner for said oxime compound The amount of the composition which is applied, the frequency of application and the period of use will vary widely dependmg upon the level of the oxime compound and/or other components of a given composition and the level of lightemng desned, e g , m light of the level of skm pigmentation present m the subject and the rate of further skin pigmentation

In a prefeπed embodiment, the composition is chronically applied to mammalian skin, preferably human skm By "chrome topical application" is meant substantially contmuous topical application of the composition over an extended penod during the subject's lifetime, preferably for a penod of at least about one week, more preferably for a penod of at least about one month, even more preferably for at least about three months, even more preferably for at least about six months, and still more preferably for at least about one year. While benefits are obtamable after vanous maximum periods of use (e.g., two, five, ten or twenty years), it is prefeπed that chrome application contmue throughout the subject's lifetime. Typically applications would be on the order of about once or twice per day over such extended periods, however application rates can vary, e.g., from about once per week up to about three tunes per day or more

A wide range of quantities of the compositions of the present mvention can be employed to provide a keratmous tissue lightemng benefit. Quantities of the present compositions which are typically applied per application are from about 0.1 mg/cm2 keratmous tissue to about 10 mg/cm2 keratinous tissue A particularly useful application amount is about 2 mg/cm2 keratmous tissue.

The method of lightemng keratmous tissue, especially skm, is preferably practiced by applymg a composition m the form of a skm lotion, cream, gel, cosmetic (such as foundation), or the like which is mtended to be left on the keratmous tissue for some esthetic, prophylactic, therapeutic or other benefit After applymg the composition to the keratmous tissue, it is preferably left on the keratmous tissue for a penod of at least about 15 minutes, more preferably at least about 30 minutes, even more preferably at least about 1 hour, most preferably for at least several hours, e.g., up to about 12 hours. The composition can also be applied to keratinous tissue, e.g., skm, under a patch (occlusive, semi-occlusive, non-occlusive) or be contamed m a patch which is then applied to the keratmous tissue. The patch can be left on the keratmous tissue for a bnef penod (e.g., approximately 5 minutes) or for an extended penod (e g., up to overnight).

Examples

The following examples further descnbe and demonstrate embodiments within the scope of the present mvention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present mvention, as many vanations thereof are possible without departing from the spirit and scope of the mvention. Example 1

A moisturizing lotion is prepared by combining the following components utilizing conventional mixing techniques.

Use of an amount of lotion sufficient to deposit about 0.04 mg/cm2 of dι-(2-furyl) ethanedione dioxnne to the keratmous tissue is appropnate.

Example 2

A lotion suitable for use on skin, hair, nails, etc is prepared by combinmg the following components utilizing conventional mixing techniques.

Use of an amount of lotion sufficient to deposit about 0.04 mg/cm2 of dι-(2-furyl) ethanedione monooxime to the keratmous tissue is appropriate.

Example 3

A cream suitable for use on skm, han, nails, etc. is prepared by combinmg the followmg components utilizing conventional mixing techniques.

Use of an amount of cream sufficient to deposit about 0.04 mg/cm2 of dι-(2-furyl) ethanedione monooxime to the keratinous tissue is appropnate.

Example 4

A gel suitable for use on skm, han, nails, etc is prepared by combinmg the followmg components utilizing conventional mixing techniques.

Use of an amount of gel sufficient to deposit about 0.04 mg/cm2 of 1 -phenyl- l,2-propanedιone-2-oxιme to the keratmous tissue is appropnate.

Claims

What is claimed ιs-

1. A method of lightemng keratinous tissue wherem said method compnses the step of topically applymg to the keratmous tissue m need of such treatment a safe and effective amount of a composition compnsmg a safe and effective amount of an oxnne compound and a dermatologically acceptable carner for the oxime compound.

2. The method of Claim 1 wherem said oxime compound has the structural formula -

M NOR³

R 1¹ — (NR «⁶)— C ' -C " -R 2² wherem -Rl and -R2 are mdependently selected from the group consisting of alkyl, aryl, and heteroaryl, wherem Rl and R2 may be covalently bonded together to form a cyclic alkyl, — M is selected from the group consistmg of =0, =S, --SR4 and -OR4 (when -M is -OR4 or -SR4, there is a hydrogen bonded to the carbon to which -M is bonded) and -R4 is selected from the group consisting of hydrogen, alkyl, aryl, and heteroaryl; — R3 is selected from the group consistmg of hydrogen, alkyl, aryl and heteroaryl; and I is selected from the group consistmg of one and zero.

3. The method of Claim 2 wherem said oxime compound is selected from the group consisting of dι-(2- furyl) ethanedione syn-monooxime, dι-(2-furyl) ethanedione anti-monooxime, and combinations thereof.

4. The method of Claim 1 wherein said oxime compound has the structural formula -

wherem =X is =0 or =S, -R7 is from 0 to 5 alkyl substituents, and -R8 is C1-C8 alkyl.

5. The method of Claim 4 wherem said oxime compound is 1 -phenyl- 1 ,2-propanedιone-2-oxιme.

6. The method of Claim 1 wherein said oxime compound has the structural formula -

wherem each X is mdependently O or S, — R7 is from 1 to 3 alkyl substituents, and -R8 is C4-C8 alkyl

The method of Claun 1 wherem said oxnne compound has the structural formula

wherem each X is mdependently O or S, no more than one -R9 is hydrogen, and one or both -R9 are mdependently from 1 to 3 alkyl substituents.

The method of Claim 1 wherem said oxime compound has the followmg structural formula:

wherem each -Rl is independently selected from the group consisting of alkyl, aryl, heteroaryl and heterocyclic, or the -Rl 's are covalently bonded together to form a cyclic alkyl ring, each heteroaryl, if any, bemg mdependently selected from the group consisting of furyl, thienyl, pyπolyl, lmidazolyl, pyrazolyl, pyrazinyl, isoquinolyl, punnyl, phthalizmyl, quinoxalinyl, furazanyl, isoxazolyl, and tetrazolyl, each heterocyclic ring, if any, bemg mdependently selected from the group consistmg of the saturated analogs of the above listed group of heteroaryl rings, wherem -R2 and -R3 are -OR4 m which case there is no bond or polar bond between -R2 and the mtrogen covalently bonded to -R3, each -R4 bemg mdependently selected from the group consisting of hydrogen, alkyl and aryl, except that both -R4's are not methyl when both -Rl's are furyl, or — R2 — is -O — and is covalently bonded to the mtrogen which is covalently bonded to -R3, and -R3 is -O — there bemg a + charge on the mtrogen to which it is bonded or ml.

The method of Claim 8 wherem said oxnne compound consists essentially of compounds wherem =NR2 and =NR3 are in amphi configuration when both -R2 and -R3 are -OH, and when both -Rl 's are furyl or the -Rl 's are covalently bonded together to form a cyclohexanedione structure

10. The method of Claim 8 wherem said oxime compound is di-(2-furyl) ethanedione amphi-dioxime, di- (2-furyl) ethanedione anti-dioxune, dι-(2-furyl) ethanedione syn-dioxime, and combinations thereof

11 The method of Claim 1 wherem said composition comprises from about 0.001% to about 20%, by weight of the composition, of the oxime compound.

12. The method of Claim 1 wherem said composition comprises from about 0.01% to about 10%>, by weight of the composition, of the oxnne compound

13. The method of Claim 1 wherem said composition comprises from about 0.1% to about 5%, by weight of the composition, of the oxnne compound

14. The method of Claim 1 wherem said composition comprises from about 0.5%> to about 5%, by weight of the composition, of the oxime compound.

15. The method of Claim 1 wherem said composition further comprises additional actives selected from the group consistmg of desquamatory actives, anti-acne actives, anti-wnnkle actives, anti-atrophy actives, anti-oxidants, radical scavengers, flavonoids, anti-mflammatory agents, anti-celluhte agents, topical anesthetics, tanning actives, additional skm lightemng agents, antimicrobial agents, antifungal agents, additional chelatmg agents, sunscreen actives, conditioning agents, thickening agents, and combmations thereof.

16. A method of lightemng keratinous tissue wherem said method comprises the step of topically applymg to the keratinous tissue m need of such treatment a safe and effective amount of a composition compnsmg a safe and effective amount of an oxnne compound selected from the group consistmg of di- (2-furyl) ethanedione syn-monooxime, dι-(2-furyl) ethanedione anti-monooxime, dι-(2-furyl) ethanedione amphi-dioxime, dι-(2-furyl) ethanedione anti-dioxime, dι-(2-furyl) ethanedione syn- dioxime, 1 -phenyl- l,2-propanedιone-2-oxιme, and combmations thereof and a dermatologically acceptable earner for the oxime compound.

17. A method of lightemng hyperpigmented regions of mammalian skm wherein said method compnses the step of topically applymg to the skm m need of such treatment a safe and effective amount of a composition compnsmg a safe and effective amount of amount of an oxnne compound and a dermatologically acceptable carner for the oxime compound.

18. The method of Claim 17 wherem said oxnne compound has the structural formula:

M NOR³

1 « ' " 2

R¹ (NR⁶)— C-C-R² wherem -Rl and -R2 are mdependently selected from the group consisting of alkyl, aryl, and heteroaryl, wherem Rl and R2 may be covalently bonded together to form a cyclic alkyl, — M is selected from the group consistmg of =0, =S, — SR4 and -OR4 (when -M is -OR4 or -SR4, there is a hydrogen bonded to the carbon to which -M is bonded) and -R4 is selected from the group consisting of hydrogen, alkyl, aryl, and heteroaryl, — R3 is selected from the group consisting of hydrogen, alkyl, aryl and heteroaryl, and 1 is selected from the group consistmg of one and zero

The method of Claim 17 wherem said oxime compound has the structural formula

wherein =X is =0 or =S, -R7 is from 0 to 5 alkyl substituents, and -R8 is C1-C8 alkyl

The method of Claim 17 wherein said oxnne compound has the followmg structural formula

wherem each -Rl is mdependently selected from the group consistmg of alkyl, aryl, heteroaryl and heterocyclic, or the -Rl 's are covalently bonded together to form a cyclic alkyl ring, each heteroaryl, if any, bemg mdependently selected from the group consisting of furyl, thienyl, pyπolyl, lmidazolyl, pyrazolyl, pyrazmyl, isoquinolyl, punnyl, phthalizinyl, quinoxalinyl, furazanyl, isoxazolyl, and tetrazolyl, each heterocyclic ring, if any, bemg mdependently selected from the group consistmg of the saturated analogs of the above listed group of heteroaryl rings, wherem -R2 and -R3 are -OR4 m which case there is no bond or polar bond between -R2 and the mtrogen covalently bonded to -R3, each -R4 bemg mdependently selected from the group consisting of hydrogen, alkyl and aryl, except that both -R4's are not methyl when both -Rl 's are furyl, or --R2 — is -O — and is covalently bonded to the mtrogen which is covalently bonded to -R3, and -R3 is -O — there bemg a + charge on the mtrogen to which it is bonded or ml