Compositions for visually improving skin

The subject invention relates to compositions which are useful for improving the visual appearance of skin, especially facial skin. The composition contains certain primary actives including at least one cyclic polyanionic polyols at least one sulfhydryl compound and at least one zwitterionic surfactant. The subject invention further relates to methods of improving the visual appearance of skin.

TECHNICAL FIELD 
The subject invention relates to the field of skin compositions for 
improving the appearance of skin. More specifically, the present invention 
relates to compositions and methods for improving the appearance of skin, 
particularly facial skin, e.g., providing a more uniform and desirable 
visual perception of the skin. 
BACKGROUND OF THE INVENTION 
More and more commonly, the population is concerned with the improvement of 
the condition of skin and particularly the appearance of skin, more 
particularly facial skin. Thus, there is high interest in decreasing the 
visual appearance of skin flaws and in increasing the evenness of skin. 
More particularly, there is an increasing and high interest in the slowing 
and/or alleviation of the visual evidence of aging skin. For example, 
aging skin is typically characterized by one or more of fine lines, 
wrinkles, age spots, dryness, scaling, loss of skin tone, sagging, 
enlarged pores, sallowness and the like. Slowing the visual appearance of 
a condition involves a decrease in the rate of appearance of such 
condition and is generally preventative, alleviation of the visual 
appearance of a condition involves treatment of an existing condition so 
as to result in a decreased visual appearance of such condition. 
Several approaches to improve skin condition have been taken over the 
years. Recently, compositions have been described as being useful for 
regulating skin wrinkles or repairing skin. For example, see U.S. Pat. No. 
5,296,500, issued to Greg G. Hillebrand on Mar. 22, 1994, and U.S. Pat. 
No. 5,434,144, issued to Gerald B Kasting and John M. Gardlik on Jul. 18, 
1995. 
While many of the compositions known in the art have provided some benefit 
with regard to skin appearance, there is an ongoing need to provide 
improved compositions for the improvement of skin appearance, more 
particularly decreasing the appearance of skin flaws and increasing the 
evenness of skin. Even more particularly, there is an increasing and high 
interest in the slowing and/or alleviation of the visual evidence of aging 
skin. There is a particular need to provide such improved compositions 
which are also mild to the skin. 
It is therefore an object of the subject invention to provide topical 
compositions for improving the visual appearance of mammalian skin. 
It is further object of the subject invention to provide such compositions 
which slow the onset of and/or alleviate the visual appearance of one or 
more skin conditions accompanying aging skin, including those conditions 
described above. 
It is yet another object to provide compositions for regulating skin 
wrinkles, e.g., which slow the onset of an/or alleviate the visual 
appearance of fine lines and/or wrinkles in mammalian skin. 
It is also an object of the subject invention to provide methods for 
improving the visual appearance of mammalian skin, for regulating wrinkles 
in mammalian skin, and for regulating atrophy of mammalian skin. 
It is yet another object to provide such compositions which are also mild 
to the skin. 
Other objects of the subject invention will be apparent from the disclosure 
which follows. 
SUMMARY OF THE INVENTION 
The subject invention involves compositions which are useful for improving 
the appearance of skin. The compositions contain a polar skin repair 
active, a sulfhydryl compound, and a zwitterionic surfactant. Preferred 
compositions contain as primary actives: 
(a) one or more polar skin repair actives selected from the group 
consisting of cyclic polyanionic polyols or a derivative thereof, sulfated 
saccharides, sulfated glycosaminoglycans, sulfonated saccharides, sulfated 
cyclodextrins, sulfonated cyclodextrins, peptides selected from the group 
consisting of tribasic tripeptides, tribasic tetrapeptides, His-Gly-Gly, 
Iamin, phosphorylated saccharides, phosphorylated cyclodextrins, 
phosphonated saccharides, phosphonated cyclodextrins, polycarboxylate 
saccharides, polycarboxylate cyclodextrins, and charged phospholipids; 
(b) one or more sulfhydryl compound(s) selected from the group consisting 
of N-acetylcysteine, cysteine, glutathione, thioglycolic acid, 
thioglycolic acid ethyl ester, thiosalicyclic acid, cysteamine, 
dithiothreitol, lipoic acid, dithioerythritol, thioacetic acid, thiolactic 
acid, mercaptoethanol, dimercaptol, monothioglycerol, 
N-(2-mercaptoproprionyl)glycine, bucillamine, mercaptomenthone, and 
cosmetically acceptable derivatives thereof; and 
(c) one or more zwitterionic surfactant(s) having the structure: 
##STR1## 
wherein (1) R.sup.1 is unsubstituted, saturated or unsaturated, straight 
or branched chain alkyl having from about 9 to about 22 carton atoms; 
(2) m is an integer from 1 to 3; 
(3) n is 0 or 1; 
(4) R.sup.2 and R.sup.3 are, independently, alkyl having from 1 to about 3 
carbon atoms, unsubstituted or mono-substituted with hydroxy; 
(5) R.sup.4 is saturated or unsaturated, straight or branched chain alkyl, 
which is unsubstituted or mono-substituted with hydroxy, having from 1 to 
about 5 carbon atoms; and 
(6) X is CO.sub.2, SO.sub.3 or SO.sub.4 ; 
and cosmetically acceptable salts thereof. 
It has surprisingly been found that the compositions of the present 
invention tend to exhibit benefits in the visual improvement of skin which 
are synergistic relative to comparable compositions containing only one or 
two of the specified groups of primary actives (namely compositions that 
do not include the polar skin repair active, the sulfhydryl compound, or 
the zwitterionic surfactant). In addition to having synergistic efficacy, 
the compositions are mild to the skin. 
The subject invention is also directed to a method of improving the visual 
appearance of skin, especially a method of regulating wrinkles in 
mammalian skin. 
These and other features, aspects and advantages of the subject invention 
will become better understood with reference to the following description 
and appended claims. 
DETAILED DESCRIPTION OF THE INVENTION 
The compositions of the present invention are useful as topical 
compositions, i.e., they are suitable for topical administration to a 
biological subject such as a mammal. The compositions of the subject 
invention are administered topically to a biological subject, i.e., by 
depositing the composition on the skin of the subject (e.g., by the direct 
laying on, spraying on or spreading of the composition on the skin). 
Topical application involves the deposition of a safe and effective amount 
of the primary actives on the skin (safe and effective amounts of the 
primary actives are left in contact with the skin). 
The topical compositions comprise a safe and effective amount of the 
primary active agents and a cosmetically acceptable topical carrier for 
the actives. 
As used herein "comprising" means that other steps and ingredients which do 
not affect the end result can be added. This term encompasses the terms 
"consisting of" and "consisting essentially of". 
As used herein, "safe and effective amount" means a sufficient amount of a 
compound, composition or other material described by this phrase to 
significantly induce a positive modification in the skin condition being 
treated, but low enough to avoid serious side effects (at a reasonable 
benefit/risk ratio), within the scope of sound judgment of the skilled 
artisan. The safe and effective amount of the compound, composition or 
other material may vary with the particular skin condition being treated, 
the age of the biological subject being treated, the severity of the 
condition, the duration of the treatment, the nature of concurrent 
therapy, the specific compound, composition or other material employed, 
the particular cosmetically acceptable carrier utilized, and like factors 
within the knowledge and expertise of the skilled artisan. 
As used herein, "primary actives," and "primary active agents" means a 
combination of at least one of the polar skin repair actives, sulfhydryl 
compounds, and zwitterionic surfactants having structure (I) described 
herein. As used herein, "polar skin repair active" means an active which 
improves the visual appearance of skin and which has a full or multiple 
ionic charge. 
As used herein, "cosmetically acceptable" means that a material (e.g., 
compound or composition) which the phrase describes is suitable for use in 
contact with the tissues of humans and lower animals without undue 
toxicity, incompatibility, instability, irritation, allergic response and 
the like, commensurate with a reasonable benefit/risk ratio. 
By "improving the visual appearance of skin", it is meant that one or more 
of the following benefits are achieved: reducing the visual appearance of 
pores (e.g., by reducing the size of pores), reducing imperfections and/or 
blemishes in skin color, including lightening hyperpigmented regions of 
skin or evening pigmentation, relieving dryness, eliminating dry rough 
spots, improving the skin's ability to retain moisture and/or protect 
itself from environmental stresses, reducing the appearance of fine lines 
and wrinkles, improving appearance and skin tone, increasing skin firmness 
and/or suppleness, decreasing skin sagging, increasing skin glow and 
clarity, increasing the skin renewal process, and/or removing vellus hair. 
Improving the visual appearance of skin may involve, for example, 
regulating wrinkles, regulating atrophy, skin lightening, regulating skin 
smoothness, and/or reducing the visual appearance of pores. 
As used herein, "regulating wrinkles" means preventing, retarding, 
arresting, or reversing the process of wrinkle or fine line formation or 
diminishing the visual appearance and/or size of wrinkles or fine lines 
tin mammalian skin. Preferred regulation of wrinkles involves diminishing 
the size of existing wrinkles and/or fine lines, i.e., reducing at least 
one dimension of wrinkles and/or fine lines, e.g., reducing the depth, 
length and/or width of existing wrinkles and/or fine lines. Regulating 
wrinkles may involve minimizing, alleviating, or slowing the onset of fine 
lines and/or wrinkles which are capable of being perceived with or without 
magnification. Other manifestations often associated with regulating 
wrinkles are a smoother feel and/or improved texture to the skin. 
As used herein "regulating atrophy" means preventing, retarding, arresting 
or reversing the process of atrophy in mammalian skin. 
As used here, "skin lightening" and "lightening the skin" means decreasing 
melanin in skin, including one or more of lightening of hyperpigmented 
skin regions including age spots, melasma, chloasma, freckles, post 
inflammatory hyperpigmentation or sun-induced pigmented blemishes. As used 
herein, "hyperpigmented region" means a localized region of darker skin, 
relative to basal skin tone. For example, the hyperpigmented region may be 
a localized region of high melanin content. 
As used herein, "regulating skin smoothness" means decreasing tactile 
and/or visual roughness and increasing tactile and/or visual smoothness of 
skin. Regulating skin smoothness may decrease the dry appearance of skin. 
The decrease in roughness and increase in smoothness may result in a more 
uniform gliding of the fingers over the skin. 
As used herein, "vellus hair" means a fine, short hair of less than 1 cm in 
length, containing little or no pigmentation. In comparison, "terminal 
hair" means coarse, pigmented, medullated hair which in its natural state 
is generally longer than a vellus hair (e.g., as seen on the scalp, 
eyebrows, eyelashes and secondary sexual hair). 
As used herein, "leave-on" means a composition that is topically applied 
without washing off for a period of typically at least several hours, 
e.g., 4-12 hours, before the skin might be washed. In contrast a 
"rinse-off" composition is intended to be rinsed from the skin soon after 
application of the composition, generally within about 30 minutes after 
application of the composition (e.g., a facial cleanser or a shower gel). 
Such rinse-off compositions are formulated so as to deposit an effective 
amount of primary actives on the skin. 
Primary Actives 
Polar Skin Repair Active 
Polar skin repair actives that are suitable for use herein are selected 
from the group consisting of cyclic polyanionic polyols, sulfated 
saccharides, sulfonated saccharides, sulfated glycosaminoglylcans, 
sulfated cyclodextrins, sulfonated cyclodextrins, peptides selected from 
tribasic tripeptides, tribasic tetrapeptides, His-Gly-Gly, and Iamin, 
phosphorylated saccharides, phosphorylated cyclodextrins, phosphonated 
saccharides, phosphonated cyclodextrins polycarboxylate saccharides, 
polycarboxylate cyclodextrins, charged phospholipids, and combinations 
thereof. Such actives, when used alone, are generally poorly delivered to 
the skin. Delivery of such actives to the skin tends to be enhanced by the 
present compositions. Preferred polar skin repair actives include the 
cyclic polyanionic polyols or derivatives described herein, sulfated 
saccharides, sulfated cyclodextrins, sulfonated cyclodextrins, and the 
peptides. 
The cyclic polyanionic polyols, sulfated saccharides, sulfated 
glycosaminoglycans, sulfonated saccharides, sulfated cyclodextrins, 
sulfonated cyclodextrins, peptides, phosphorylated saccharides, 
phosphorylated cyclodextrins, phosphonated saccharides, phosphonated 
cyclodextris, polycarboxylate saccharides, polycarboxylate cyclodextrins 
and charged phospholipids are particularly effective for regulating skin 
wrinkles, especially effacing existing wrinkles or fine lines, regulating 
atrophy, and/or for reducing the sallow appearance of skin. The cyclic 
polyanionic polyols are also effective in evening skin tone, particularly 
in reducing under-eye circles. 
Cyclic polyanionic polyols or derivatives thereof which are suitable for 
use herein are those having the structure: 
##STR2## 
wherein n is 1, 2 or 3 and each X is, independently, selected from the 
group consisting of OSO.sub.3.sup.-, OPO.sub.3.sup.2-, SO.sub.3.sup.-, 
PO.sub.3.sup.2-, CO.sub.2.sup.-, and OH. At least three X are other than 
OH, ore preferably at least four X, more preferably still at least five X, 
most preferably six X. When n is 1 or 2, all X are, preferably other than 
OH. All X which are other than OH are preferably the same. Cyclic 
polyanionic polyols and derivatives of this type which are suitable for 
use herein are described in U.S. Pat. No. 5,434,144, issued to Kasting and 
Gardlik on Jul. 18, 1995, incorporated herein by reference. 
The cyclic polyanionic polyol or derivative is neutralized by an 
appropriate amount of a pharmaceutically-acceptable cation so as to 
balance the charge. The cation is selected from a group including (but are 
not limited to) H.sup.+, Na.sup.+, K.sup.+, Ca.sup.++, Mg.sup.++, Al.sub.2 
(OH).sub.5.sup.+, NH.sub.4.sup.+, (HOCH.sub.2 CH.sub.2).sub.3 NH.sup.+, 
(CH.sub.3 CH.sub.2)NH.sup.+, HOCH.sub.2 (CH.sub.3).sub.2 CNH.sub.3.sup.+, 
(HOCH.sub.2).sub.3 CNH.sub.3.sup.+, CH.sub.3 (HOCH.sub.2).sub.2 
CNH.sub.3.sup.+, CH.sub.3 CH.sub.2 (HOCH.sub.2).sub.2 CNH.sub.3.sup.+, 
(CH.sub.3 CH.sub.2).sub.4 N.sup.+, C.sub.16 H.sub.33 (CH.sub.3).sub.3 
N.sup.+ and (N--C.sub.16 H.sub.33)C.sub.5 H.sub.4 N.sup.+, and mixtures 
thereof. 
Sulfated saccharides that are suitable for use herein include sucrose 
ostasulfate, sorbitol hexasulfate, trehalose sulfate, inositol 
hexasulfate, dulcitol hexasulfate, mannitol hexasulfate, ribitol 
pentasulfate, xylitol pentasulfate, D-threitol tetrasulfate, 
pentaerythritol tetrasulfate, meso-erythritol tetrasulfate, glycerol 
trisulfate, dextran sulfate, and combinations thereof. In general, the 
more sulfation the greater the improvement in skin appearance. Preferred 
sulfated saccharides contain at least five sulfate groups. Sucrose 
octasulfate is preferred. 
Sulfated glycosaminoglycans that are suitable for use herein include 
heparin, heparan sulfate, dermatan sulfate, sulodexide, mesoglycan, and 
combinations thereof. 
Sulfated or sulfonated cyclodextrins that are suitable for use herein 
include alpha, beta, and gamma cyclodextrins with an average degree of 
substitution of from about 4 to about 12, 14 or 16, respectively, 
sulfobutylether derivatives of beta cyclodextrin and 
hydroxypropyl-beta-cyclodextrin with a degree of substitution of from 
about 4 to about 14, and combinations thereof. 
Suitable peptides for use in the present invention include tribasic 
tripeptides and tribasic tetrapeptides, including but not limited to 
Peptide E (Arg-Ser-Arg-Lys), Peptide CK (Arg-Lys-Arg), Peptide CK+ 
(Ac-Arg-Lys-Arg-NH.sub.2); the peptides His-Gly-Gly and Iamin, and 
combinations thereof. Peptide E (Arg-Ser-Arg-Lys), Peptide CK 
(Arg-Lys-Arg), Peptide CK+ (Ac-Arg-Lys-Arg-NH.sub.2), His-Gly-Gly, Iamin 
and combinations thereof are preferred. Suitable tribasic tripeptides and 
tetrapeptides include those described in U.S. patent application Ser. No. 
08/082,847, "Compositions For Regulating Wrinkles Comprising a Peptide" 
filed in the names of Andrew W. Fulmer and Charles C. Bascom on Jun. 25, 
1993, allowed on Aug. 24, 1995, which is incorporated herein by reference. 
Charged phospholipids that are suitable for use as the polar skin repair 
active include lysophosphatidic acid, 2- fluorolysophosphatidic acid, 
2-deoxylysophosphatidic acid, and combinations thereof. Lysophosphatidic 
acid and 2-fluorolysophosphatidic acid are preferred. A detailed 
description of suitable charged phospholipids is provided in U.S. Pat. No. 
5,340,568, issued to Mazur et al. on Aug. 23, 1994, incorporated herein by 
reference. 
Additional polar skin repair actives that are suitable for use herein 
include sulfonated saccharides; phosphorylated saccharides; phosphorylated 
cyclodextrins; phosphonated saccharides; phosphonated cyclodextrins; 
polycarboxylate saccharides; and polycarboxylate cyclodextrins. Exemplary 
polycarboxylate cyclodextrins are succinylated beta-cyclodextrin and 
carboxymethyl beta-cyclodextrin. Currently preferred polar skin repair 
actives are the cyclic polyanionic polyols or derivatives having the 
structure described above. Preferred actives of this structure are those 
in which n is 1 or 2; X is OSO.sub.3.sup.- or OPO.sub.3.sup.2-, all non-OH 
X's are the same, and the cation is H.sup.+, Na.sup.+, K.sup.+, 
NH.sub.4.sup.+, (HOCH.sub.2 CH.sub.2).sub.3 NH.sup.+, HOCH.sub.2 
(CH.sub.3).sub.2 CNH.sub.3.sup.+, (HOCH.sub.2)CNH.sub.3.sup.+, CH.sub.3 
(HOCH.sub.2).sub.2 CNH.sub.3.sup.+, or a combination thereof. More 
preferred actives of this type are those in which n is 2, X is 
OPO.sub.3.sup.2-, all non-OH X's are the same, and the cation is H.sup.+, 
Na.sup.+, K.sup.+, NH.sub.4.sup.+, HOCH.sub.2 (CH.sub.3).sub.2 
CNH.sub.3.sup.+, (HOCH.sub.2).sub.3 CNH.sub.3.sup.+, CH.sub.3 
(HOCH.sub.2).sub.2 CNH.sub.3.sup.+, or a combination thereof. Even more 
preferably, the cations is Na.sup.+, K.sup.+, and/or NH.sub.4.sup.+, with 
Na.sup.+ being more preferred than K.sup.+ which is more preferred than 
NH.sub.4.sup.+. Mixtures of Na.sup.+ and K.sup.+ are highly preferred. 
Where the cyclic polyanionic polyols are used as a skin repair active, it 
will generally be preferred to neutralize the composition to a pH of from 
3 to 8, more preferably 5 to 7, such that H.sup.+ will also be present. 
Preferred cyclic polyanionic polyols for use herein include: 
1,2,3,4,5,6-cyclohexanehexaphosphoric acid (scyllo, myo or other inositol 
hexakis phosphoric acid derivatives), having the structure: 
##STR3## 
myo-inositol hexakisphosphate, calcium salt myo-inositol hexakisphosphate, 
dimagnesium tetrapotassium salt 
myo-inositol hexakisphosphate, magnesium potassium salt 
myo-inositol hexakisphosphate, dipotassium salt 
myo-inositol hexakisphosphate, monopotassium salt 
myo-inositol hexakisphosphate, dodecasodium salt 
myo-inositol hexakisphosphate, triethanolamine salt 
myo-inositol hexakisphosphate, ammonium salt 
myo-inositol hexakisphosphate, cetylpyridinium salt 
myo-inositol hexakisphosphate, cetyltrimethylammonium salt 
myo-inositol-1,3,4,5,6-pentakisphosphate, ammonium salt 
myo-inositol-1,2,5,6-tetrakisphosphate, ammonium salt 
myo-inositol-1,3,4,5-tetrakisphosphate, ammonium salt 
myo-inositol-1,3,4,6-tetrakisphosphate, ammonium salt 
myo-inositol-3,4,5,6-tetrakisphosphate, ammonium salt 
myo-inositol-1,4,5-trisphosphate, potassium salt 
myo-inositol-1,3,4-trisphosphate, ammonium salt 
myo-inositol-1,5,6-trisphosphate, ammonium salt 
myo-inositol-2,4,5-trisphosphate, ammonium salt 
1,2,3,4,5,6-cyclohexanchexasulfuric acid (scyllo, myo or other inositol 
hexakis sulfuric acid derivatives), having the structure: 
##STR4## 
myo-inositol hexakissulfate, sodium salt myo-inositol hexakissulfate, 
hexasodium salt 
myo-inositol hexakissulfate, potassium salt 
myo-inositol hexakissulfate, hexapotassium salt 
myo-inositol hexakissulfate, ammonium salt 
myo-inositol hexakissulfate, triethanolamine salt 
myo-inositol hexakissulfate, cetylpyridinum salt 
myo-inositol hexakissulfate, cetryltrimethylammonium salt 
myo-inositol pentakissulfate, ammonium salt 
myo-inositol tetrakissulfate, ammonium salt 
myo-inositol trissulfate, potassium salt 
myo-inositol-1,2,3-trissulfate-4,5,6-trisphosphate, sodium salt 
1,2,3,4,5,6-cyclohexanehexaphosphonic acid, having the structure: 
##STR5## 
1,2,3,4,5,6-cyclohexanehexasulfonic acid, having the structure: 
##STR6## 
1,2,3,4,5,6-cyclohexanehexacarboxylic acid, having the structure: 
##STR7## 
1,2,3,4,5-cyclopentanepentasulfuric acid, having the structure: 
##STR8## 
1,2,3,4,5-cyclopentanepentaphosphoric acid, having the structure: 
##STR9## 
1,2,3,4,5,6,7-cycloheptaneheptasulfuric acid, having the structure: 
##STR10## 
1,2,3,4,5,6,7-cycloheptaneheptaphosphoric acid, having the structure: 
##STR11## 
and the salts of the foregoing structures. 
More preferred cyclic polyanionic polyols include myo-inositol hexakis 
phosphoric acid, myo-inositol hexakis sulfuric acid and myo-inositol 1,2,3 
trissulfate--4,5,6-trisphosphate. Even more preferred cyclic polyanionic 
polyols include myo-inositol hexakis phosphoric acid and myo-inositol 
hexakis sulfuric acid. The more preferred cyclic polyanionic polyol is 
myo-inositol hexakis phosphoric acid. 
Sulfhydryl Compound 
The composition of this invention also comprise a sulfhydryl compound. As 
used herein "sulfhydryl compound" means a compound which contains an S-H 
group and which is capable of donating a hydrogen atom. The compositions 
may include one or more of the sulfhydryl compounds. 
As well understood in the art, sulfhydryl compounds may exist in various 
derivative forms through tautomerism, di- or oligomerization through 
hydrogen bonds, hydration, or other spontaneous rearrangements, including 
the anionic S.sup.- form. As used herein, "sulfhydryl compound" includes 
such other forms. If, in the sulfhydryl compounds useful in the invention, 
several mesomeric or tautomeric forms are conceivable, only one mesomeric 
or tautomeric form will be given for characterization, in accordance with 
conventional chemical nomenclature, with other forms intended to be 
embodied thereby. In general, the form as it naturally exists will be 
preferred. 
As used herein, "sulfhydryl compound" includes the following derivatives of 
the sulfhydryl compounds: (i) cosmetically acceptable salts of the 
sulfhydryl compound and (ii) cosmetically acceptable hydrocarbyl esters of 
the sulfhydryl compound. The latter refers to carboxyl esters of those 
sulfhydryl compounds which also contain a carboxylic acid group with an 
alcohol consisting of a hydrocarbon with at least one hydroxyl group 
attached. 
Cosmetically acceptable salts of the sulfhydryl compound include, but are 
not limited to alkali metal salts, e.g., sodium, lithium, potassium and 
rubidium salts; alkaline earth metal salts, e.g., magnesium, calcium and 
strontium salts; ammonium salts; trialkylammonium salts, e.g., 
trimethylammonium and triethylammonium; and tetralkylonium salts. 
Preferred cosmetically acceptable salts of the sulfhydryl compound include 
Na.sup.+, K.sup.+, Ca.sup.++, Mg.sup.++, Al.sub.2 (OH).sub.5.sup.+, 
NH.sub.4.sup.+, (HOCH.sub.2 CH.sub.2).sub.3 NH.sup.+, (CH.sub.3 
CH.sub.2).sub.3 NH.sup.+, (CH.sub.3 CH.sub.2).sub.4 N.sup.+, C.sub.12 
H.sub.25 (CH.sub.3).sub.3 N.sup.+ and C.sub.12 H.sub.25 (C.sub.5 H.sub.4 
N).sub.3 N.sup.+ salts. More preferred salts of the sulfhydryl compound 
include Na.sup.+, K.sup.+, NH.sub.4.sup.+, and (HOCH.sub.2 CH.sub.2).sub.3 
NH.sup.+ salts. Most preferred salts of the sulfhydryl compound include 
Na.sup.+ and NH.sub.4.sup..varies. salts. Suitable salts of the sulfhydryl 
compound are described, for example, in U.S. Pat. No. 5,296,500, issued to 
Hillebrand on Mar. 22, 1994, incorporated herein by reference. 
Cosmetically acceptable hydrocarbyl esters of sulfhydryl compounds include 
carboxyl esters of the sulfhydryl compound with primary, secondary, and 
tertiary aliphatic alcohols containing from 1 to about 24 carbon atoms, 
unsaturated primary alcohols containing from about 10 to about 24 carbon 
atoms, and aryl and alkylaryl alcohols containing one or more aromatic 
rings. Examples of suitable alcohols include but are not limited to: 
methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, 
sec-butanol, n-pentanol, n-hexanol, n-heptanol, n-octanol, 2-ethylhexanol, 
n-decanol, lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl 
alcohol, olelyl alcohol, linoleyl alcohol, linolenyl alcohol, behenyl 
alcohol, cyclohexanol, and benzyl alcohol. Preferred alcohols are ethanol, 
n-propanol, ispropanol, n-butanol, isobutanol, sec-butanol, 
2-ethylhexanol, lauryl alcohol, myristyl alcohol, stearyl alcohol, oleyl 
alcohol, and benzyl alcohol. Most preferred are ethanol, isopropanol, 
sec-butanol, and benzyl alcohol. 
Exemplary sulfhydryl compounds include N-acetyl-cysteine, cysteine, 
glutahlione, thioglycolic acid, thioglycolic acid ethyl ester, 
thiosalicylic acid, cysteamine, dithiothreitol, lipoic acid, 
dithioerythritol, thioacetic acid, thiolactic acid, mercaptoethanol, 
dimercaptol, monothloglycerol, N-(2-mercaptoproprionyl)glycine, 
bucillamine, mercaptomenthone, and cosmetically acceptable derivatives 
thereof. Preferred sulfhydryl compounds are selected from the group 
consisting of: 
a) N-acetyl-L-cysteine, having the structure: 
##STR12## 
b) glutathione, having the structure: 
##STR13## 
c) dithiothreitol, having the structure: 
##STR14## 
d) dithioerythritol, having the structure: 
##STR15## 
e) cysteine, having the structure: 
##STR16## 
f) thioglycolic acid; g) thioglycolic acid ethyl ester; 
h) thiosalicylic acid (2-mercaptobenzoic acid); 
i) cysteamine; 
j) lipoic acid; and 
j) cosmetically acceptable derivatives of the foregoing compounds. 
While the aforementioned, preferred sulfhydryl compounds are shown in their 
protonated forms, it is meant to include the other forms of these 
compounds which are known to exist. 
More preferred sulfhydryl compounds useful in the subject invention include 
N-acetylcysteine (especially the D and L isomers), cysteine (especially 
the D and L isomers), glutathione, dithiothreitol, dithioerythritol, and 
cosmetically acceptable derivatives of the foregoing compounds. The most 
preferred sulfhydryl compound is N-acetyl-L-cysteine or a cosmetically 
acceptable derivative thereof. 
Zwitterionic Surfactant 
The compositions of the present invention also contain a zwitterionic 
surfactant. Suitable zwitterionic surfactants include long chain 
(preferably C.sub.9 -C.sub.22) betaines and sultaines. 
As used herein, "zwitterionic surfactant" includes cosmetically acceptable 
salts of the zwitterionic surfactants described herein. Preferred 
cosmetically acceptable salts include alkali metal salts, alkaline earth 
metal salts, non-toxic heavy metal salts, boron salts, silicon salts, 
ammonium salts, trialkylammonium salts, and tetralkylammonium salts such 
as described hereinabove in reference to the sulfhydryl compound. 
Preferred zwitterionic surfactants are those having the structure: 
##STR17## 
In structure (I) R.sup.1 is unsubstituted, saturated or unsaturated, 
straight or branched chain alkyl having from about 9 to about 22 carbon 
atoms. Preferred R.sup.1 has from about 11 to about 18 carbon atoms; more 
preferably from about 12 to about 16 carbon atoms; more preferably still 
from about 14 to about 16 carbon atoms. 
In structure (I), m is an integer from 1 to 3, preferably 2 or 3; more 
preferably 3. 
In structure (I), n is either 0 or 1; n is preferably 0. 
In structure (I), R.sup.2 and R.sup.3 are, independently, selected from the 
group consisting of alkyl having from 1 to about 3 carbon atoms, 
unsubstituted or mono-substituted with hydroxy. Preferred R.sup.2 and 
R.sup.3 are CH.sub.3. 
In structure (I), X is selected from the group consisting of CO.sub.2, 
SO.sub.3 and SO.sub.4. 
In structure (I), R.sup.4 is selected from the group consisting of 
saturated or unsaturated, straight or branched chain alkyl, unsubstituted 
or mono-substituted with hydroxy, having from 1 to about 5 carbon atoms. 
When X=CO.sub.2, R.sup.4 preferably has 1 or 3 carbon atoms, more 
preferably 1 carbon atom. When X=SO.sub.3 or SO.sub.4. R.sup.4 preferably 
has from about 2 to about 4 carbon atoms, more preferably 3 carbon atoms. 
Preferred zwitterionic surfactants of the subject invention include the 
following compounds: 
a) cetyl betaine, having the structure: 
##STR18## 
b) stearyl betaine, having the structure: 
##STR19## 
c) cocoamidopropylbetaine, having the structure: 
##STR20## 
wherein R.sup.1 is unsubstituted, saturated, straight chained alkyl with 
from about 9 to about 13 carbon atoms; 
d) cetyl propyl hydroxy sultaine, having the structure: 
##STR21## 
e) cocoamidopropyl hydroxy sultaine, having the structure: 
##STR22## 
wherein R.sup.1 has from about 9 to about 13 carbon atoms; and f) behenyl 
betaine, having the structure: 
##STR23## 
One or more zwitterionic surfactants may be used in the present invention. 
More preferred zwitterionic surfactants of the subject invention include 
cetyl betaine, stearyl betaine, cocoamidopropyl betaine, cetyl propyl 
hydroxy sultaine or mixtures thereof. Still more preferred zwitterionic 
surfactants of the subject invention include cetyl betaine, stearyl 
betaine, cocoamidopropyl betaine or mixtures thereof. The zwitterionic 
surfactant is even more preferably cetyl betaine and/or stearyl betaine. 
The most preferred zwitterionic surfactant of the subject invention is 
cetyl betaine. 
Preferred Compositions 
The compositions of the present invention comprise at least one of each of 
the polar skin repair actives, sulfhydryl compounds, and zwitterionic 
surfactants according to structure (I) described herein above in safe and 
effective amounts. The compositions preferably comprise from about 0.01% 
to about 10% of polar skin repair active, from about 0.1% to about 20% of 
sulfhydryl compound, and from about 0.1% to about 10% of zwitterionic 
surfactant according to structure (I). More preferred compositions 
comprise from about 0.05% to about 5% of polar skin repair active, from 
about 0.2% to about 10% of sulfhydryl compound, and from about 0.2% to 
about 5% of said zwitterionic surfactant. Most preferred compositions 
comprise from about 0.1% to about 5% of polar skin repair active, from 
about 0.5% to about 5% of sulfhydryl compound, and from about 0.5% to 
about 2% of said zwitterionic surfactant. 
Cosmetically Acceptable Carrier 
The phrase "cosmetically acceptable carrier", as used herein, means one or 
more compatible solid or liquid fillers, diluents, extenders and the like, 
which are cosmetically acceptable as defined herein. The term 
"compatible", as used herein, means that the components of the 
compositions of this invention are capable of being comingled with the 
primary actives of the present invention, and with each other, in a manner 
such that there is no interaction which would substantially reduce the 
efficacy of the composition under ordinary use situations. The type of 
carrier utilized in the present invention depends of the type of product 
desired. The topical compositions useful in the subject invention may be 
made into a wide variety of product types. These include, but are not 
limited to, lotions, creams, gels, sticks, sprays, ointments, pastes, 
mousses and cosmetics (e.g., solid, semi-solid, liquid make-up, including 
foundations). These product types may comprise several types of carriers 
including, but not limited to solutions, aerosols, emulsions (including 
water-in-oil and oil-in-water), gels, solids, and liposomes. 
Solutions according to the subject invention typically include a 
cosmetically acceptable aqueous or organic solvent which is capable of 
having the primary actives dispersed or dissolved therein. Water is a 
preferred solvent. Examples of suitable organic solvents include: 
propylene glycol, polyethylene glycol (e.g., Molecular Weight 200-600 
g/mole), polypropylene glycol (e.g., Molecular Weight 425-2025 g/mole), 
glycerol, 1,2,4-butanetriol, sorbitol esters, 1,2,6-hexanetriol, ethanol, 
isopropanol, sorbitol esters, butanediol, and mixtures thereof. Solutions 
useful in the subject invention preferably contain from about 80% to about 
99.99% of an acceptable aqueous or organic solvent and the primary actives 
in the above described amounts. 
Aerosols according to the subject invention can be formed by adding a 
propellant to a solution such as described above. Exemplary propellants 
include chloro-fluorinated lower molecular weight hydrocarbons. Additional 
propellants that are useful herein are described in Sagarin, Cosmetics 
Science and Technology, 2nd Edition, Vol. 2, pp. 443-465 (1972), 
incorporated herein by reference. Aerosols are typically applied to the 
skin as a spray-on product. 
Emulsions according to the present invention generally contain a solution 
as described above and a lipid or oil. Lipids and oils may be derived from 
animals, plants, or petroleum and may be natural or synthetic (i.e., 
man-made). Preferred emulsions also contain a humectant, such as glycerin. 
Emulsions will preferably further contain from about 1% to about 10%, more 
preferably from about 2% to about 5%, of an emulsifier, based on the 
weight of the carrier. Emulsifiers may be nonionic, anionic or cationic. 
Suitable emulsifiers are disclosed in, for example, U.S. Pat. No. 
3,755,560, issued Aug. 28, 1973, Dickert et al., U.S. Pat. No. 4,421,769, 
issued Dec. 20, 1983, Dixon et al.; and McCutcheon's Detergents and 
Emulsifiers, North American Edition, pages 317-324 (1986), each 
incorporated herein by reference. 
The emulsion may also contain an anti-foaming agent to minimize foaming 
upon application to he skin. Anti-foaming agents include high molecular 
weight silicones and other materials well known in the art for such use. 
The emulsions preferably comprise a silicone for imparting a preferred skin 
feel. Generally such silicones have a low molecular weight. Suitable such 
silicones include cyclomethicones, dimethicones, and blends such as Dow 
Corning 200 fluid (especially 10 cs) and Dow Corning Q2-1401. Such 
silicones are commercially available from the Dow Corning Corp. of 
Midland, Mich. 
Preferred emulsions have a high viscosity, of from about 10,000 to about 
300,000 centipoise, more preferably from about 20,000 to about 200,000 
centipoise, most preferably from about 50,000 to about 150,000 centipoise. 
The topical compositions of the subject invention may comprise a topical 
cosmetically acceptable emollient. Such compositions preferably contain 
from about 2% to about 50% of the emollient. As used herein, "emollient" 
refers to a material used for the prevention or relief of dryness, as well 
as for the protection of the skin. A wide variety of suitable emollients 
are known and may be used herein. Segarin, Cosmetics Science and 
Technology, 2nd Edition, Vol. 1, pp. 32-43 (1972), incorporated herein by 
reference, contains numerous examples of materials suitable as an 
emollient. 
Lotions and creams according to the present invention generally comprise a 
solution carrier system and one or more emollients. Lotions typically 
comprise 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 the primary actives in the above described 
amounts. A cream typically comprises 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 primary 
actives in the above described amounts. 
In addition to the primary actives, ointments of the present invention may 
comprise a simple carrier base of animal or vegetable oils or semi-solid 
hydrocarbons (oleginous), absorption ointment bases which absorb water to 
form emulsion, or water soluble carriers, e.g., a water soluble solution 
carrier. Ointments may further comprise a thickening agent, such as 
described in Sagarin, Cosmetics Science and Technology, 2nd Edition, Vol. 
1, pp. 72-73 (1972), incorporated here by reference, and/or an emollient. 
For example, an ointment may comprise from about 2% to about 10% of an 
emollient; from about 0.1% to about 2% of a thickening agent; and the 
primary actives in the above described amount. 
Compositions of this invention useful for cleansing ("cleansers") are 
formulated with a suitable carrier, e.g., as described above, and 
preferably contain, in addition the primary actives in the above described 
amounts, from about 1% to about 90%, more preferably from about 5% to 
about 10%, of a cosmetically acceptable surfactant. The surfactant is 
suitably selected from anionic, nonionic, zwitterionic, amphoteric and 
ampholytic surfactants, as well as mixtures of these surfactants. Such 
surfactants are well known to those skilled in the detergency art and are 
generally selected for their detergency action, mildness to the skin, and 
compatibility with the primary actives. Nonlimiting examples of suitable 
surfactants include isoceteth-20, sodium methyl cocoyl taurate, sodium 
methyl oleoyl taurate, and sodium lauryl sulfate. See U.S. Pat. No. 
4,800,197, to Kowcz et al., issued Jan. 24, 1989, which is incorporated 
herein by reference in its entirety, for exemplary surfactants useful 
herein. Examples of a broad variety of additional surfactants useful 
herein are described in McCutcheon's Detergents and Emulsifiers, North 
American Edition (1986), published by Allured Publishing Corporation, 
which is incorporated herein by reference in its entirety. The cleansing 
compositions can optionally contain, at their art-established levels, 
materials which are conventionally used in cleansing compositions. 
The physical form of the cleansing compositions is not critical. The 
compositions can be, for example, formulated as toilet bars, liquids, 
shampoos, pastes, or mousses. Toilet bars are most preferred since this is 
the form of cleansing agent most commonly used to wash the skin. Rinse-off 
cleansing compositions, such as shampoos, require a delivery system 
adequate to deposit sufficient levels of actives on the skin or scalp. A 
preferred delivery system involves the use of insoluble complexes. For a 
more complete disclosure of such delivery systems, see U.S. Pat. No. 
4,835,148, Barford et al., issued May 30, 1989, incorporated herein by 
reference in its entirety. 
The compositions of the present invention are preferably formulated to have 
a pH of 8.5 or below. The pH values of these compositions preferably range 
from about 2 to about 8.5, more preferably from about 3 to about 7, most 
preferably from about 4.5 to about 5.5. Compositions have a pH within the 
range of about 4.5 to 7 tend to exhibit less skin irritation, less odor, 
and greater shelf stability relative to corresponding compositions having 
a pH of greater than about 8.5. Preferred emulsions of the invention are 
formulated at intermediate pH values, preferably from about 3 to about 7, 
more preferably about 4.5 to about 5.5. 
Optional Ingredients 
The compositions of this invention may contain other ingredients, including 
but not limited to preservatives, preservative enhancers, and actives in 
addition to the primary actives. Any optional ingredients should be 
compatible with the primary active agents such that the activity of the 
primary actives does not decrease unacceptably, preferably not to any 
significant extent, over a useful period (preferably at least one year, 
more preferably at least two years, under normal storage conditions). 
Preferred compositions contain a preservative, preservative enhancer, zinc, 
and/or a zinc salt as described herein. These agents may be incorporated 
into the aforementioned formulations in the amounts described herein. 
For example, certain agents may decrease the activity of the sulfhydryl 
compound, particularly N-acetyl-L-cysteine, over time. First, an excessive 
number of microbes may decrease the activity of the sulfhydryl compound, 
for example by microbial metabolism of the compound. Second, it has been 
found that formaldehyde can chemically react with the sulfhydryl compound 
to decrease its activity. Thus, when a composition containing the 
sulfhydryl compound is formulated with formaldehyde or a formaldehyde 
forming preservative or other material, the composition may have decreased 
activity of the sulfhydryl compound over time relative to the 
corresponding formulation that does not contain formaldehyde or a compound 
capable of forming formaldehyde. Therefore, it is desirable to provide 
compositions containing sulfhydryl compounds that are resistant to 
microbial contamination and which do not include formaldehyde or 
formaldehyde forming preservatives or other materials. 
The compositions of this invention are therefore preferably substantially 
free of formaldehyde and materials that may form or release formaldehyde 
when present in the composition, including preservatives that may form or 
release formaldehyde in the composition. Formaldehyde and materials that 
may form or release formaldehyde in the composition are alternatively 
referred to herein as "formaldehyde donor(s)." As used herein, 
"substantially free of formaldehyde donors" means that there are no 
detectable formaldehyde donors, preferably no formaldehyde donors. The 
presence of formaldehyde donors may be indicated by the presence of 
formaldehyde in the composition by any suitable analytical technique, for 
example high pressure liquid chromatography (HPLC). The presence of such 
donors may be detected initially or evidenced by the generation of 
formaldehyde over time. Preferred compositions are those which evidence no 
formaldehyde upon storage over a period of at least 2 months at 45.degree. 
C., when measured using a sensitive analytical method such as HPLC. 
Preservatives 
The topical compositions of the invention preferably comprise one or more 
preservatives. Preferred preservatives are those which are substantially 
free of formaldehyde donors. Thus, the preservatives preferred for use 
herein are those that do not form or release formaldehyde in the 
composition either in the process of preserving or in an unrelated 
process. In contrast, formaldehyde forming or releasing preservatives form 
or release formaldehyde in the composition either in the process of 
preserving or in an unrelated process. 
Most preferred preservatives include benzyl alcohol, propylparaben, 
ethylparaben, butylparaben, methylparaben, benzylparaben, isobutylparaben, 
phenoxyethanol, ethanol, sorbic acid, benzoic acid, 
methylchloroisothiazolinone, methylisothiazolinone (a preservative 
containing a mixture of methylchloroisothiazolinone and 
methylisothiazolinone being commercially available, for example, from Rohm 
& Haas as Kathon CG.RTM.), methyl dibromoglutaronitrile (commercially 
available, for example, from Calgon as Tektamer 38.RTM.), dehydroacetic 
acid, o-phenylphenol, sodium bisulfite, dichlorophen, salts of any of the 
foregoing compounds, and mixtures of any of the foregoing compounds. 
Even more preferred preservatives are selected from the group consisting of 
benzyl alcohol, propylparaben, methylparaben, phenoxyethanol, 
methylchloroisothiazolinone, methylisothiazolinone, benzoic acid, salts of 
any of the foregoing preservatives, and mixtures of any of the foregoing 
compounds. 
Still more preferred preservatives are benzyl alcohol, propylparaben, 
methylparaben, phenoxyethanol and mixtures thereof. Yet even more 
preferably, the preservative is a mixture of propylparaben and methyl 
paraben with either or both of benzyl alcohol and phenoxyethanol. In 
addition to stability of the sulfhydryl compound, these mixtures provide 
broad preservative efficacy with no or only minimal risk of skin 
irritation to the user. Most preferably, the preservative is a mixture of 
benzyl alcohol, propylparaben and methylparaben. In addition to stability 
of the sulfhydryl compound and broad preservative efficacy, this mixture 
presents a particularly low risk of skin irritation to the user. 
The use of the foregoing preservatives that are substantially free of 
formaldehyde donors is described in more detail in the copending U.S. 
patent application Ser. No. 08/479,879, entitled "Topical Compositions 
Comprising N-Acetyl-L-Cysteine," filed on Jun. 7, 1995 in the names of 
Greg G. Hillebrand and Marcia S. Schnicker, which is incorporated herein 
by reference in its entirety. The foregoing preservatives are preferably 
used in the compositions of this invention in the same amounts as 
described for the compositions of the just referenced patent application. 
Preservative Enhancer 
The compositions of this invention containing a preservative also 
preferably comprise a safe and effective amount of a preservative 
enhancer. As used here, "preservative enhancer" means an agent whose 
purpose is to enhance the activity of the preservative. As will be 
understood by the artisan having ordinary skill, the preservative enhancer 
does not itself typically provide a level of preservative efficacy 
preferred for commercial products; rather it tends to increase the 
efficacy of the preservative. Enhancement of the preservative efficacy may 
involve chelation. Preferred preservative enhancers useful in the present 
invention include ethylenediaminetetraacetic acid (EDTA), butylene glycol, 
propylene glcol, ethanol, and mixtures thereof. Where the preservative 
includes a paraben, e.g., methyl or propyl paraben, EDTA is the preferred 
preservative enhancer. The use of such enhancers is described in more 
detail in the above-referenced and incorporated copending U.S. patent 
application Ser. No. 08/479,879. The preservative enhancers are preferably 
used in the compositions of this invention in the amounts described for 
the compositions of the patent application Ser. No. 08/479,879. For 
example, a currently preferred composition comprises about 0.3% EDTA, 
based on the weight of the composition. 
Zinc Compound 
The compositions of the invention preferably contain zinc or a zinc salt 
which may complex with the sulfhydryl compound. Without intending to be 
bound or limited by theory, the zinc most likely removes odor by 
complexing with malodorous H.sub.2 S which may be formed in trace amounts 
as the sulfhydryl compound decomposes. The zinc may additionally or 
alternatively increase the stability of the sulfhydryl compound. The use 
of zinc salts in a manner which is suitable for the present invention is 
further described in U.S. Pat. No. 5,296,600, Hillebrand, issued on Mar. 
22, 1994, which is incorporated herein by reference. Preferred zinc salts 
are zinc oxide and zinc citrate. 
Thickeners 
The zwitterionic surfactant tends to decrease the viscosity of the 
composition. Therefore, a thickener may be employed in the compositions of 
the invention to thicken the composition and/or to minimize the risk of 
phase separation. Exemplary thickeners include cetyl hydroxyethylcellulose 
(e.g., Natrosol Plus 330, commercially available from Aqualon of 
Wilmington, Del.) and those thickeners commercially available under the 
trade name SALCARE from Allied Colloids of Bradford, England. A preferred 
thickener is SALCARE 95, which is a mixture of polyquaternium-37 (a 
polymeric quaternary amine), mineral oil and PPG-1 trideceth-6 
(polyoxypropylene/polyoxyethylene ether of tridecyl alcohol generally 
having the formula C.sub.13 H.sub.27 (OCHCH.sub.3 CH.sub.2).sub.x 
(CH.sub.2 CH.sub.2).sub.y OH, where x is 1 and y is 6). The thickener 
should be compatible with the components of the composition or otherwise 
be employed in relatively low levels so as to not significantly decrease 
the efficacy of the zwitterionic surfactant over a useful commercial 
period. Typically, about 0.1 to about 0.5% thickener is employed. 
Other Actives 
The compositions of the subject invention may optionally comprise other 
actives capable of functioning in different ways to enhance the benefits 
of the primary actives and/or to provide other benefits. Examples of such 
substances include, but are not limited to anti-inflammatory agents, 
antimicrobial agents, anti-androgens, sunscreens, sunblocks, 
anti-oxidants/radical scavengers, chelators, anti-dandruff agents, organic 
hydroxy acids, light diffusion agents, and pigments. 
A. Anti-Inflammatory Agents 
A safe and effective amount of an anti-inflammatory agent may be added to 
the compositions useful in the subject invention, 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 skin appearance 
benefits of the present invention, e.g., such agents contribute to a more 
uniform and acceptable skin tone. The exact amount of anti-inflammatory 
agent to be used in the compositions will depend on the particular 
anti-inflammatory agent utilized since such agents vary widely in potency. 
Steroidal anti-inflammatory agents, including but not limited to, 
corticosteroids such as hydrocortisone, hydroxyltriamcinolone, 
alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethasone 
dipropionate, clobetasol valerate, desonide, desoxymethasone, 
desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone 
diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, 
fludocortisone, flumethasone privalate, fluocinolone acetonide, 
fluocinonide, flucortine butylesters, fluocotolone, fluprednidene 
(fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone 
acetate, hydrocortisone butyrate, methylprednisolone, tramcinolone 
acetonide, cortisone, cortodoxone, fluctonide, fludrocortisone, 
difluorosone diacetate, fluradrenolone, fludrocortisone, difluorosone 
diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, 
betamethasone and the balance of its esters, chloroprednisone, 
chlorprednisone acetate, clorotelone, clescinolone, dichlorisone, 
difluprednate, flucloronide, flunisolide, floromethalone, fluperolone, 
fluprednisolone, hydrocortisone valerate, hydrocortisone 
cyclopentylpropionate, hydrocortamate, meprednisone, paramethasone, 
prednisolone, prednisone, beciomethasone dipropionate, trimcinolone, and 
mixtures thereof may be used. The preferred steroidal anti-inflammatory 
for use is hydrocortisone. 
A second class of anti-inflammatory agents which is useful in the 
compositions includes the nonsteroidal anti-inflammatory agents. The 
variety of compounds encompassed by this group are well-known to those 
skilled in the art. For detailed disclosure of the chemical structure, 
synthesis, side effects, etc. of non-steroidal anti-inflammatory agents, 
reference may be had to standard texts, including Anti-inflammatory and 
Anti-Rheumatic Drugs, K. D. Rainsford, Vol. I-III, CRC Press, Boca Raton, 
(1985), and Anti-inflammatory Agents, Chemistry and Pharmacology, 1, R. A. 
Scherrer, et al., Academic Press, N.Y. (1974), each incorporated herein by 
reference. 
Specific non-steroidal anti-inflammatory agents useful in the composition 
invention include, but are not limited to: 
1) the oxicams, such as piroxicam, isoxicam, tenoxicam, sudoxicam, and 
CP-14,304; 
2) the salicylates, such as aspirin, disalcid, benorylate, trilisate, 
safapryn, solprin, diflunisal, and fendosal; 
3) the acetic acid derivatives, such as diclofenac, fenclofenac, 
indomethacin, sulindac, tometin, isoxepac, furofenac, tiopinac, 
zidometacin, acematacin, fentiazac, zomepirac, clindanac, oxepinac, 
felbinac, and ketorolac; 
4) the fenamates, such as mefanamic, meclofenamic, flufenamic, niflumic, 
and tolfenamic acids; 
5) the propionic acid derivatives, such as ibuprofen, naproxen, 
benoxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufen, indopropfen, 
piroprofen, carprofen, oxaprozin, pranoprofen, microprofen, tioxaprofen, 
suprofen, alminoprofen, and tiaprofenic; and 
6) the pyrazoles, such as phenylbutazone, oxyphenbutazone, feprazone, 
azapropazone, and trimethazone. 
Mixtures of these non-steroidal anti-inflammatory agents may also be 
employed, as well as the cosmetically acceptable salts and esters of these 
agents. For example, etofenamate, a flufenamic acid derivative, is 
particularly useful for topical application. Of the nonsteroidal 
anti-inflammatory agents, ibuprofen, naproxen, flufenamic acid, mefenamic 
acid, meclofenamic acid, piroxicam and felbinac are preferred; ibuprofen, 
naproxen, and flufenamic acid are most preferred. 
Finally, so-called "natural" anti-inflammatory agents are useful in methods 
of the subject invention. For example, candelilla wax, alpha bisabolol, 
aloe vera, Manjistha (extracted from plants in the genus Rubia, 
particularly Rubia Cordifolia), and Guggal (extracted from pants in the 
genus Commiphora, particulary Commiphora Mukul), may be used. 
B. Retinoids 
A safe and effective amount of a retinoid may be added to the compositions 
of the subject invention, preferably from about 0.001% to about 0.5%, more 
preferably from about 0.01% to about 0.1% of the composition. As used 
herein, "retinoid" includes all natural and/or synthetic analogs of 
Vitamin A or retinol-like compounds which possess the biological activity 
of Vitamin A in the skin as well as the geometric isomers and steroisomers 
of these compounds, such as all-trans retinoic acid and 13-cis-retinoic 
acid. The retinoid is preferably retinol, retinal, or retinoic acid, more 
preferably retinol. 
The retinoids enhance the skin appearance benefits of the present 
invention. For example, the retinoids may diminish fine lines, wrinkles, 
other textural discontinuities, or skin color discontinuities. 
C. Antimicrobial Agents 
As used herein, "antimicrobial agent" means a compound capable of 
destroying microbes, preventing the development of microbes or preventing 
the pathogenic action of microbes. The antimicrobial agent enhances the 
skin appearance benefits of the present invention. A safe and effective 
amount of an antimicrobial agent may be added to compositions of the 
subject invention, preferably from about 0.001% to abut 10%, more 
preferably from about 0.01% to about 5%, also from about 0.05% to about 1% 
or 2% of the compositions. Preferred antimicrobial agents useful in the 
subject invention are benzoyl peroxide, erythromycin, tetracycline, 
clindamycin, azelaic acid, and sulfur resorcinol. 
D. Antiandrogens 
As used herein, "anti-androgen" means a compound capable of correcting 
androgen-related disorders by interfering with the action of androgens at 
their target organs. The target organ for the subject invention is 
mammalian skin. 
E. Sunscreens and Sunblocks 
Exposure to ultraviolet light can result in excessive scaling, texture 
changes and other changes of the stratum corneum. Therefore, the 
compositions of the subject invention preferably contain a sunscreen or 
sunblock to enhance the skin appearance benefits of the invention. The 
sunscreens/sunblocks tend to provide photoprotection, thus preventing, 
retarding or arresting sunlight ultraviolet radiation-induced damage to 
the skin, such as sunburn, blistering, peeling skin wrinkling, skin 
cancer, agent spots, irregular pigmentation, rough texture, and dryness. 
Suitable sunscreens or sunblocks may be organic or inorganic. 
A wide variety of conventional sunscreening agents are suitable for use 
herein. Sagarin, et al., at Chapter VIII, pages 189 et seq., of Cosmetics 
Science and Technology (1972), discloses numerous suitable agents, and is 
incorporated herein by reference. Specific suitable sunscreening agents 
include, for example: p-aminobenzoic acid, its salts and its derivatives 
(ethyl, isobutyl, glyceryl esters; p-dimethylaminobenzoic acid); 
anthranilates (i.e., o-amino-benzoates; methyl, menthyl, phenyl, benzyl, 
phenylethyl, linalyl, terpinyl, and cyclohexenyl esters); salicylates 
(amyl, phenyl, octyl, benzyl, menthyl, glyceryl, and di-pro-pyleneglycol 
esters); Cinnamic acid derivatives (menthyl and benzyl esters, a-phenyl 
cinnamonitrile; butyl cinnamoyl pyruvate); dihydroxycinnamic acid 
derivatives (umbeliferone, methylumbelliferone, 
methylaceto-umbelliferone); trihydroxycinnamic acid derivatives 
(esculetin, methylesculetin, daphnetin, and the glucosides, esculin and 
daphnin); hydrocarbons (diphenylbutadiene, stilbene); dibenzalacetone and 
benzalacetophenone; naphtholsulfonates (sodium salts of 
2-naphtol-3,6-disulfonic and of 2-naphthol-6,8-disulfonic acids); 
di-hydroxynaphthoic acid and its salts; o- and 
p-Hydroxybiphenyldisulfonates; coumarin derivatives (7-hydroxy, 7-methyl, 
3-phenyl); diazoles (2-acetyl-3-bromoindazole, phenyl benzoxazole, methyl 
naphthoxazole, various aryl benzothiazoles); quinine salts (bisulfate, 
sulfate, chloride, olcate, and tannate); quinoline derivatives 
(8-hydroxyquinoline salts, 2-phenylquinoline); hydroxy- or 
methoxy-substituted benzophenones; uric and vilouric acids; tannic acid 
and its derivatives (e.g., hexaethylether); (butyl carbotol) (6-propyl 
piperonyl) ether; hydroquinone; benzophenones (oxybenzene, sulisobenzone, 
dioxybenzone, benzoresorcinol, 2,2',4,4'-tetrahydroxybenzophenone, 
2,2'-dihydroxy-4,4'-dimethoxybenzophenone, octabenzone; 
4-isopropyldibenzoylmethane; butylmethoxydibenzoylmethane; etocrylene; 
3-(4'-methylbenzylidene bornan-2-one) and 4-isopropyl-di-benzoylmethane. 
Of these, 2-ethylhexyl-p-methoxycinnamate, 4,4'-t-butyl 
methoxydibenzoyl-methane, 2-hydroxy-4-methoxybenzophenone, 
octyldimethyl-p-aminobenzoic acid, digalloyltrioleaic, 
2,2-dihydroxy-4-methoxybenzophenone, 
ethyl-4-(bis(hydroxy-propyl))aminobenzoate, 
2-ethylhexyl-2-cyano-3,3-diphenylacrylate, 2-ethylhexyl-salicylate, 
glyceryl-p-aminobenzoate, 3,3,5-tir-methylcyclohexylsalicylate, 
methylanthranilate, p-dimethyl-aminobenzoic acid or aminobenzoate, 
2-ethylhexyl-p-dimethyl-amino-benzoate, 2-phenylbenzimidazole-5-sulfonic 
acid, 2-(p-dimethylaminophenyl)-5-sulfonicbenzoxazoic acid and mixtures of 
these compounds, are preferred. 
Most preferred sunscreens useful in the compositions useful in the subject 
invention are 2-ethylhexyl-p-methoxycinnamate, 
butylmethoxydibenzoylmethan, 2-hydroxy-4-methoxybenzophenone, 
octyldimethyl-p-aminobenzoic acid and mixtures thereof. 
Also particularly useful in the compositions are sunscreens such as those 
disclosed in U.S. Pat. No. 4,937,370 issued to Sabatelli on Jun. 26, 1990, 
and U.S. Pat. No. 4,999,186 issued to Sabatelli & Spirnak on Mar. 12, 
1991, both of which are incorporated herein by reference. The sunscreening 
agents disclosed therein have, in a single molecule, two distinct 
chromophore moieties which exhibit different ultra-violet radiation 
absorption spectra. One of the chromophore moieties absorbs predominantly 
in the UVB radiation range and the other absorbs strongly in the UVA 
radiation range. 
Preferred members of this class of sunscreening agents are 
4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester of 
2,4-dihydroxybenzophenone; N,N-di-(2-ethylhexyl)-4-aminobenzoic acid ester 
with 4-hydroxydibenzoylmethane; 4-N,N-(2-ethylhexyl)methylaminobenzoic 
acid ester with 4-hydroxydibenzoylmethane; 
4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester of 
2-hydroxy-4-(2-hydroxyethoxy)dibenzoylmethane; 
N,N-do-(2-ethylhexyl)-4-aminobenzoic acid ester of 
2-hydroxy-4-(2-hydroxyethoxy)benzophenone; and 
N,N-di-(2-ethylhexyl)-4-aminobenzoic acid ester of 
4-(2-hydroxyethoxy)dibenzoylmethane and mixtures thereof. 
Suitable inorganic sunscreens or sunblocks include metal oxides, e.g., zinc 
oxide and titanium dioxide. For example, the sue of titanium dioxide in 
topical sunscreen compositions that is applicable to the present invention 
is described in copending application Ser. No. 08/448,942, filed on May 
24, 1995, in the names of Jiang Yue, Lisa R. Dew and Donald L. Bissett, 
incorporated herein by reference. 
A safe and effective amount of the sunscreen or sunblock is used, typically 
from about 1% to about 20%, more typically from about 2% to about 10%. 
Exact amounts will vary depending upon the sunscreen chosen and the 
desired Sun Protection Factor (SPF). 
An agent may also be added to any of the compositions useful in the subject 
invention to improve the skin substantivity of those compositions, 
particularly to enhance their resistance to being washed off by water, or 
rubbed off. A preferred agent which will provide this benefit is a 
copolymer of ethylene and acrylic acid. Compositions comprising this 
copolymer are disclosed in U.S. Pat. No. 4,663,157, Brock, issued May 5, 
1987, which is incorporated herein by reference. 
F. Anti-Oxidants/Radical Scavengers 
While the sulfhydryl compound (e.g., glutahione) may itself impart 
anti-oxidant properties to the composition, preferred compositions of the 
subject invention include an anti-oxidant/radical scavenger as an active 
in addition to the primary active agents. The anti-oxidant/radical 
scavenger enhances the skin appearance benefits of the present invention. 
For example, such agents provide protection against radiation which can 
cause increased scaling, texture changes or other changes in the stratum 
corneum and against other environmental agents which can cause skin 
damage. Anti-oxidants/radical scavengers tend to prevent, retard or arrest 
the damaging effects of oxygen radicals, whether arising from the 
environment (such as smoke, pollution, or ultraviolet radiation exposure) 
or from endogenous sources (such as products from normal metabolism), on 
the skin. Such damage includes sunburn, blistering, peeling, skin 
wrinkling, skin cancer, skin sagging, skin yellowing, age spots, irregular 
pigmentation, rough texture, and dryness. 
A safe and effective amount of an anti-oxidant/radical scavenger may be 
added to the compositions of the subject invention, 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 it 
salts, tocopherol (vitamin E), tocopherol sorbate, other esters of 
tocopherol, butylated hydroxy benzoic acids and their salts, 
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (commercially 
available under the tradename Trolox.RTM.), gallic acid and its alkyl 
esters, especially propyl gallate, uric acid and its salts and alkyl 
esters, sorbic acid and its salts, the ascorbyl esters of fatty acids, 
amines (e.g., N,N-diethylhydroxylamine, amino-guanidine), dihydroxy 
fumaric acid and its salts, green tea polyphenols, and proanthrocyanidine 
(commercially available as PYCNOGENOL from M. W. International, Inc. of 
West Hillside, N.J.) may be used. Preferred anti-oxidants/radical 
scavengers are selected from tocopherol sorbate, and esters of tocopherol, 
and PYCNOGENOL, most preferably the antioxidant is tocopherol sorbate. For 
example, the use of tocopherol sorbate in topical compositions and 
applicable to the present invention is described in U.S. Pat. No. 
4,847,071, issued on Jul. 11, 1989 to Donald L. Bissett, Rodney D. Bush 
and Ranjit Chatterjee, incorporated herein by reference. 
G. Chelators 
As used herein, "chelating agent" means an active agent capable of removing 
a metal ion from a system by forming a complex so that the metal ion 
cannot readily participate in or catalyze chemical reactions. The 
chelating agent enhances the skin appearance benefits of the present 
invention. The chelating agent tends to be particularly effective in 
providing photoprotection. For example, the chelating agent provides 
protection against UV radiation which can contribute to excessive scaling 
or skin texture changes and against other environmental agents which can 
cause skin damage. 
A safe and effective amount of a chelating agent may be added to the 
compositions of the subject invention, preferably from about 0.1% to about 
10%, more preferably from about 1% to about 5%, of the composition. 
Chelators useful herein are disclosed in U.S. patent application Ser. No. 
619,805, Bissett, Bjush & Chatterjee, filed Nov. 27, 1990 (which is a 
continuation of U.S. patent application Ser. No. 251,910, filed Oct. 4, 
1988); U.S. patent application Ser. No. 514,892, Bush & Bissett, filed 
Apr. 26, 1990; and U.S. patent application Ser. No. 657,847, Bush, Bissett 
& Chatterjee, filed Feb. 25, 1991; all incorporated herein by reference. 
Preferred chelators useful in compositions of the subject invention are 
furldioxime, Octopirox (commercially available from Hoeschst of Germany), 
furilmonoxime, chelator L1 (1,2-dimethyl-3-hydroxy-pyrid-4-one), 
deferoxamine (commercially available as DESFERAL from Ciba-Geigy of 
Aardsley, N.Y.), and derivative thereof. More preferred chelators are 
furildioxime, furilmonoxime, chelator L1 and deferoxamine, most preferred 
chelators are furildioxime, chelator L1 and deferoxamine. 
H. Anti-dandruff Actives 
An anti-dandruff agent may be included in compositions of the present 
invention that are intended for application to the scalp. Anti-dandruff 
agents prevent and treat the effects of flaking on the scalp. A 
particularly preferred anti-dandruff agent is zinc pyridinethione. 
I. Organic Hydroxy Acids 
The compositions of the present invention 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%, of an organic hydroxy acid such as 
salicylic acid, glycolic acid, or lactic acid. Salicylic acid is 
preferred. The organic hydroxy acids enhance the skin appearance benefits 
of the present invention. For example, the organic hydroxy acids tend to 
improve the texture of the skin. 
J. Other Combination Actives 
The compositions of the present invention may also include a natural 
extract of yeast, rice bran, or other natural extracts such as are known 
in the art. Such extracts enhance the skin appearance benefits of the 
present invention, and are preferably used in an amount of from 0.1% to 
about 20%, more preferably 0.5% to about 10%, also from 1% to about 5%. A 
natural extract of yeast is preferred. 
The compositions may also comprise a vitamin B (including but not limited 
to niacin, niacinamide, pyridoxine or mixtures thereof) or vitamin B 
complex. 
K Light Diffusion Agents and Pigments 
The compositions of the present invention may also include finely divided 
particulate solids that scatter, diffuse, or absorb light. Such 
ingredients when used as appropriate levels may enhance the skin 
appearance benefits of the present invention, and are preferably used in a 
an amount of from 0.01% to about 20%, more preferably from about 0.05% to 
about 5%, also from about 0.1% to about 1%. A preferred light diffusion 
agent is titanium dioxide. An examplary pigment is red iron oxide 
(Fe.sub.2 O.sub.3). Additional pigments suitable for use with the present 
invention are described in Harry's Cosmetology, 7th Ed. (Wilkinson and 
Moore, Eds.), Chemical Publishing Co., N.Y. (1982), incorporated herein by 
reference. 
Preparation of Compositions 
The compositions of the present invention are generally prepared by 
conventional methods such as are known in the art of making topical 
compositions. Such methods typically involve mixing of the ingredients to 
a relatively uniform state, with or without heating, cooling, application 
of vacuum, and the like. Exemplary methods are described in Remington's 
Pharmaceutical Sciences, 17th Ed. (A. R. Gennaro, Ed.), Mack Publishing 
Company, Easton Pa., 1985, pp. 301-329, 1492-1517, incorporated herein by 
reference. For optimum stability of the sulfhydryl compound, the 
compositions of this invention should be manufactured, packaged and stored 
in a manner which avoids simple air oxidation of the sulfhydryl compound. 
Thus, exposure of the compositions to air during manufacture, packaging 
and storage should be minimized. Techniques for minimizing such exposure 
are well known in the art, and include, e.g., the use of inert gas 
atmospheres or vacuum conditions. 
Delivery Methods for the Topical Compositions 
The topical compositions useful for the method of the instant invention can 
be delivered from a variety of delivery devices. The following are three 
nonlimiting examples. 
A. Application Pads 
The compositions useful herein can be incorporated into an application pad, 
e.g., a cleansing pad. Preferably these application pads comprise from 
about 50% to about 75% by weight of one or more layers of nonwoven fabric 
material and from about 20% to about 50% by weight of a liquid composition 
of the present invention deliverable from the nonwoven fabric material. 
Pads useful in the present invention are described in detail in U.S. Pat. 
No. 4,891,228, to Thaman et al., issued Jan. 2, 1990; and U.S. Pat. No. 
4,891,227, Thaman et al., issued Jan. 2, 1990; both of which are 
incorporated by reference herein in their entirety. 
B. Dispensing Devices 
The compositions of the present invention can also be incorporated into an 
delivered from a dispensing device, e.g., a soft-tipped or flexible 
dispensing device. Such devices are useful for the controlled delivery of 
the compositions to the skin surface and have the advantage that the 
composition itself never need be directly handled by the user. Nonlimiting 
examples of these devices include a fluid container having a mouth, an 
applicator, means for holding the applicator in the mouth of the 
container, and a normally closed pressure-responsive valve for permitting 
the flow of fluid (the composition) from the container to the applicator 
upon the application of pressure to the valve. The valve can include a 
diaphragm formed from an elastically fluid impermeable material with a 
plurality of non-intersecting arcuate slits therein, where each slit has a 
base which is intersected by at least one other slit, and where each slit 
is out of intersecting relation with its own base, and wherein there is a 
means for disposing the valve in the container inside of the applicator. 
Examples of these applicator devices are described in U.S. Pat. No. 
4,693,623, to Schwartzman, issued Sep. 15, 1987; U.S. Pat. No. 4,620,648, 
to Schwartzman, issued Sep. 15, 1987; U.S. Pat. No. 2,669,323, to Harker 
et al., issued Jun. 13, 1972; U.S. Pat. No. 3,418,055, to Schwartzman, 
issued Dec. 24, 1968; and U.S. Pat. No. 3,410,645, to Schwartzman, issued 
Nov. 12, 1968; all of which are incorporated herein by reference in their 
entirety. Examples of applicators useful herein are commercially available 
from Dab-O-Matic, Mount Vernon, N.Y. 
C. Cathodal iontophoresis 
Where the primary active comprises a negatively-charged active, e.g. the 
cyclic polyanionic polyols, another preferred method of the subject 
invention involves application of a safe and effective amount of the 
primary actives in a conductive cream or gel, followed by controlled 
application of an electric field having a polarity such as to drive the 
negatively-charged active into the skin. This method, known as cathodial 
iontophoresis, is described in A. K. Banga and Y. W. Chien, "Iontophoretic 
Delivery of Drugs; Fundamentals, Developments, and Biomedical 
Applications" J. Controlled Release Vol. 7, pp. 1-24 (1988) and reference 
therein, incorporated herein by reference. Further examples are given in 
R. R. Burnett, "Iontophoresis," J. Hadgraft and R. H. Guy (editors), 
Transdermal Drug Delivery; Development Issues and Research Initiatives, 
Marcel Dekker, New York, N.Y. 1989, pp. 247-291 and references therein and 
in G. B. Kasting, E. W. Merritt, and J. C. Keister, "An In Vitro Method 
for Studying the Iontophoretic Enhancement of Drug Transport Through 
Skin," Journal of Membrane Science, Vol. 35, pp. 137-159, (1988), and 
reference therein, incorporated herein by reference. In such a method the 
composition is applied to the skin and contacted by the cathode of an 
electrical device suitable for delivering a controlled voltage or current 
to the skin. The circuit is completed by placing the anode of the device 
on the skin at a point removed from the site of delivery. The electrical 
field (i.e., voltage or current) may be either pulsed, sinusoidal, or 
continuous wave as described in the above references. The duration of 
application of the field ranges from about 1 minute to about 24 hours, 
preferably from about 1 to about 30 minutes, more preferably from about 2 
to about 5 minutes. A series of high voltage pulses followed by continuous 
cathodic iontophoresis as described in M. R. Prausnitz, V. G. Bose, R. 
Langer, and J. C. Weaver, "Electroporation of Mammalian Skin: A Mechanism 
to Enhance Transdermal Drug Delivery," Proceedings of the National Academy 
of Sciences (USA), Vol. 90, pp. 10504-10508, (1993) and references 
therein, incorporated herein by reference, may also be used. In all cases 
the electric field is applied in a safe and effective manner, so that the 
anionic active is delivered across the skin without undue discomfort or 
irritation to the subject. 
Methods For Improving the Visual Appearance of Skin 
The subject invention relates to methods of improving the visual appearance 
of skin. Such methods comprise topically applying to the skin an effective 
amount of the compositions of the subject invention so as to deposit an 
effective amount of the primary actives on the skin. The term "effective 
amount", as used herein, means an amount sufficient to provide a skin 
appearance benefit as defined herein after single or multiple application, 
generally multiple application. In general, a safe and effective amount of 
the primary actives are left in contact with the skin for a period 
sufficient to provide noticeable benefits after single or multiple 
application, typically multiple application such as described herein. 
Typically, the primary actives are left in contact with the skin for a 
period of at least several hours (e.g. about 4 to about 12 hours) before 
washing of the skin might be done. The composition can be applied for 
several hours, days, weeks, months or years at appropriate intervals. The 
compositions are preferably applied from about three times a day to about 
once every three days, more preferably from about twice a day to once 
every other day, also preferably about once a day until a satisfactory 
skin appearance improvement has been achieved. Improvements in skin 
appearance may be observed with or without magnification by a variety of 
methods such as are known in the art, including image analysis, expert 
grading, self assessment, replicas, and histology. Exemplary methods of 
assessing improvements in skin appearance are described by Warren et al. 
in "Age, Sunlight, and Facial Skin: A Histologic and Quantitative Study", 
the Journal of the American Academy of Dermatology, 1991; 25: 751-60, 
which is incorporated herein by reference. 
Typically, in each application, an effective coating of the skin with the 
primary actives is achieved by topically applying (in terms of mg 
active/cm.sup.2 skin) from about 0.001 mg/cm.sup.2 of a sulfhydryl 
compound, and from about 0.004 mg/cm.sup.2 to about 0.1 mg/cm.sup.2 of 
zwitterionic surfactant having structure (I). More preferably, from about 
0.02 mg/cm.sup.2 to about 0.06 mg/cm.sup.2 of each of the primary actives 
is applied. For example, about 0.04 mg/cm.sup.2 of each of the primary 
actives may be applied. 
The compositions can be used as a leave-on product or the skin may be 
rinsed soon after application of the compositions to the skin, e.g., 
compositions in the form of rinse-off cleansers. 
The compositions are generally applied by lightly massaging the composition 
into the skin, which may or may not be followed by cathodal iontophoresis.