Skin Research and Technology 1995; 1: 115-122
Printed in Denmark. All rights reserved
Mechanism of action of a lipophilic derivative of salicylic
acid on normal skin
J. L. LkvGque', P. Corcuff', G. Gonnordl, C. Montastier', B. Renault', R. Bazin', G. Pikrard3 and
M. C. Poelman4
'Laboratories de Recherche de L'OREAL, Aulnay-Sous-Bois, France, 'Laborntoires de Recherche de L'OREAL, Chevilly-Larue, France, 3Service de
Dermatopathologie/CHU du Sart Tilman, Li&e, Belgium, 4Facult6 de Pharmacie/Paris V, Paris, France
Backgroundaims: Keratolytics are agents used for a very long
period of time to improve various skin disorders such as acne,
hyperkeratoses, ichtyose etc. Very little is known about their
mechanism of action on healthy skin. On man, the chronic appli-
cation of a cosmetic cream containing a lipophilic derivative of
Salicyclic acid (LSA) markedly improves the aspect and texture
of the skin. Different methods were used to investigate the mech-
anisms of action of this new compound, compared to salicyclic
acid.
Methods: Both non-invasive and histologic methods were used
on the dorsal forearm of human volunteers treated with the prod-
ucts. Concerning the non-invasive methods, TEWL, silflo replica
and confocal microscopy were used. On shave biopsies, various
histometric parameters were measured by image analysis after
different staining. The use of antibody MIB-1 reacting with the
proliferating nuclear antigen Ki 67 allows one to measure the
epidermis proliferation index.
Results: Compared to the excipient alone, presence of LSA 1%
salicylic acid (SA) has long been used in
A LTHOUGH
cosmetology and treatment of a wide range of
skin disorders (acne, hyperkeratosis, etc.), published
reports suggest that it is very difficult to determine its
precise mechanism of action. The term "keratolytic"
chosen to define its clear beneficial action appears to
sum up our knowledge in this field. Indeed, while
there are many publications describing the efficacy of
this compound in the various skin diseases mentioned
above, those reporting its effect on normal skin are far
less numerous (1-3). These studies showed a rela-
tively small increase in desquamation, with no change
in the mitotic activity of the epidermis.
There are now several commercial preparations
containing SA for normal skin care and other "kerato-
lytic" agents, whose short-term effects on the skin ap-
parently boil down to an increase in softness. For our
part, we have attempted to optimize the effect of SA
by making it more lipophilic. As shown below,
chronic application of this product leads to a consider-
Cowright 0 Miinkspaard 1995
Skin Research and Technology
ISSN 0909-752X
improves smoothness and firmness of the skin. The appearance
in terms of clearness and healthy complexion is also improved.
The thickening of all the living epidermis layers is obtained by
both histometric measurement and confocal microscopy. This
acanthosis is only recorded on the LSA-treated zones. The Ki 67
labelling study shows that LSA significantly increases the skin
proliferation index.
Conclusions: Salicylic acid, and more markedly its lipophilic de-
rivative (LSA), appear to have a significative effect on the re-
newal of the living epidermis. This probably explains the cos-
metic improvement of the skin obtained after a 1-month treat-
ment with a cream containing this new molecule.
Key words: lipophilic salicylic acid - healthy complexion - con-
focal microscopy - histometry - aging.
0 Munksgaard, 1995
Accepted for publication 2 March 1995
able clinical improvement in the aspect and "feel" of
the skin. We thought it is highly unlikely that all the
observed ameliorations were simply due to increased
desquamation, even if this mode of action accounts
for some effects.
With the aim of identifying the underlying mechan-
isms involved in these clinical improvements,we under-
took two types of investigation: noninvasive measure-
ments, followed by examination of skin sections by con-
ventional and immunofluorescence microscopy.
The non-invasive methods included confocal micro-
scopy in vivo, which permits direct visualisation of
the epidermis, layer by layer, and measurement of
both the thickness of the stratum corneum and that of
the living epidermis.
Material and Methods
Table 1 summarizes the experimental protocols used
to study the impact of this lipophilic salicylic acid de-
115
LkvCque et al.
TABLE 1. Summa y of the various experiments carried out on the healthy volunteers
Experiment no. In-vivo experimental approach on humans
Volunteerslsite Duration Applied products'
1 12/forearm2 2 weeks SA 5%/LSA 1.5%Iexcipient
2 12/forearm 4 weeks LSA 1.5%/excipient/controI
3 6/forearm 2 weeks LSA 1.5%/SA 0.78%/excipient
4 6lforearm 4 weeks LSA 1.5%1SA 5%/excipient/control
5 35lface 3 months LSA 1%
6 80/face 6 months KSA 1%/excipient*
O M emulsion: 2 mg/cm2, 2 x a day.
Randomized sites on the forearm (dorsal side).
Analogue scale.
4-grade scale.
* Contained 5% glycerol.
rivative (LAS) on human skin. These studies com-
prised clinical evaluations, noninvasive measure-
ments and biopsy examination (see Table 1).
CIinical studies
Two main studies were carried out.
35 volunteers (women aged between 30 and 65
years) were recruited by the dermatology unit of
LiPge University Hospital (Belgium). This inclusion
criteria included the presence, on the face, of marked
signs of aging such as fine lines and wrinkles, dry skin
and mottled pigmentation. The volunteers applied an
O/W emulsion containing 1%LSA to the face.
At times TO, T1, T2 and T3 months, the quality of
the skin was evaluated by the volunteers themselves
and by the clinician. The latter assessed softness,
suppleness, hydration and firmness on rating scales
from 0 to 4. The volunteers assessed the same criteria,
plus radiance and the presence of fine lines, using vis-
ual rating scales (Experiment 5).
80 women aged between 30 and 65 years were re-
cruited. They were divided into 2 groups of 40, each
group applying an excipient (O/W emulsion contain-
ing 5% glycerol) with or without 1% LSA. At TO, the
volunteers were asked to evaluate, on a 15 cm visual
rating scale, the cosmetic state of their skin on the
basis of the following parameters: firmness, radiance,
softness, "healthiness" and hydration.
The same evaluation was made after one, four and
six months of application, in the morning after wash-
ing and in the evening (Experiment 6).
Noninvasive measurements
Noninvasive measurements were made on the fore-
arm (exterior side) in the various experimental con-
ditions summarized in Table 1. The areas to which the
products were applied and the untreated control areas
116
Techniques
TEWL
confocal microscopy - replicas
TEWL
biopsies
self appraisal3 - clinical
assessment4
self appraisal3
were randomly allocated to the upper and lower parts
of the two forearms.
We used the following devices:
TEWL: SERVOMED EVAPORIMETER@
Replicas: Negative replicas were obtained with SIL-
FLO@(Flexico, UK)
A JEOL 200 scanning microscope was used
during the 1st week of application (experi-
ment no. 2)
Confocal microscopy. We used a prototype developed
in our laboratories from a Tracor Northern tandem
scanning microscope (TSM) (4, 5). A surface contact
device was designed to assume surface applanation
and limit any shift caused by patient movement and
blood flow.
A 50X/0.85 N.A. Nikon oil immersion objective
lens was chosen as an acceptable compromise be-
tween magnification, resolution and working dis-
tance. The light source was a 100-watt mercury arc
lamp with an UV and IR filtering system to respect
the non-invasive nature of the method. Image capture
was performed using a low-light camera (DAGE MTI
SIT 68) coupled to a Sony U-Matic video recorder
(PAL).The video images were transferred to a Quanti-
met 520 image analyser. After image-by-image selec-
tion, each image was digitized in a 512x512 pixel ar-
ray. Fast Fourier transformation was used to eliminate
the scanning lines generated by the Nipkow disk.
Skin layers thicknesses were measured using the
contact system. The vertical position of the objective
was controlled by a stepping motor, each step corre-
sponding to a vertical displacement of 0.9 pm. Height
data are displayed in overlay and recorded together
with the confocal image in real time via a mixing im-
age processor.
Technical details regarding the recognition of the
different skin interfaces are given in (4).
 Lipophilic derivative of salicylic acid and normal skin

Biopsy processing
Shave biopsies were taken from the four test sites and
from a control area of the forearms. They were fixed
in Cornoy medium and embedded in paraffin. Sec-
tions five microns thick were prepared and stained
with haematoxylin-eosin and with PAS-colloidal iron.
Other sections were deparaffinized in xylol or toluene
and a graded series of alcohol. Endogenous peroxi-
dase was blocked with 3% hydrogen peroxide in
methanol. Immunohistochemistry was performed
with the APAAP method. The following antibodies
were used: L-1823 (prediluted, Dako) against 56 and
64 kDa keratins, and MIB-1 (1:20, Immunotech) re-
acting with the proliferation nuclear antigen Ki-67.
Computerized image analysis of tissue sections was
performed using a MOP videoplan (KONTRON, Ech-
ing, Germany).

Studied compound
The experiments were designed to evaluate the cos-
metic efficacy and the mechanism of action of a new
lipophilic salicylic acid derivative of the following for-
mula:

Fig. 1. Improvement of the skin after 1, 2 and 3 months of treatment

with an excipient containing 1% LSA. Asssessment by the panelists
acid and assessment by the dermatologist (experiment no. 5).

LSA:
hydroxy
This compound (MW=264.3) is poorly soluble in
water. It is thus solubilized in a synthetic oil then in-
troduced into the oil phase of a nonionic O / W emul-
sion. The same emulsion was used to test SA at 5%
and 0.78% in comparative studies with LSA.
Informed consent
All the experiments in this study were carried out fol-
lowing the ethical standards of the participating .cen-
ters: the PARIS V Faculty of Pharmacy and the SART
TILMAN Hospital, Li2ge, Belgium.
Documents concerning the nature of the test prod-
ucts, their toxicological dossiers and the experimental
protocols were supplied, and the volunteers gave
their informed consent.
Statistical analysis
This was determined by means of two-way analysis
of variance (times, products).
Results
Clinical assessment and self-appraisal
(experiments nos. 5 and 6 )
Fig. 1 represents the % ameliorations assessed by the
dermatologist and the volunteers for a number of cos-
metic parameters. The dermatologist considered that
the main improvement was, in decreasing order:
smoothness, hydration, suppleness and firmness. No
significant effect on fine lines was observed. The vol-
unteers also found that smoothness was mostly im-
proved, followed by hydration and radiance, then
wrinkles and suppleness. These effects were marked
and appeared within the first month in the view of
both the determatologist and the volunteers. Further
improvements occurred until the 3rd month with re-
gard to softness and fine lines, suggesting an effect on
the deeper skin layers.
These results were impressive, but were not ob-
tained comparatively to an excipient.
In the following study, cosmetic efficacy was judged
relative to an excipient containing a moisturizing
compound, glycerol, at 5% (Fig. 2). No difference was

117
LCvCque et al.

1
1.5
0 Exclplent (n = 40)

20
Exciplent + LSA 1% (n = 40)

-6
.
Ll
1.3

T
t
Skin
Finnnesr
Complexion
Clearness u Healthy
Complexion
U

Smoothness .9
0.78% 1.5 %
-
5% 1.5%
SA LJA SA LSA
Fig. 2. Improvement of the skin of 80 volunteers after 6 months of V
6 mM
treatment. 40 were treated with an excipient containing 5% glycerol,
and the other forty with the same excipient containing 1% LSA (ex- Fig. 4. Increase of TEWL after 2 weeks of treatment of an excipient
periment no. 6). containing L S A 1.5% or SA 0.78%. This corresponds to the same
molar concentration 5.7 mM. When compared to the same weight con-
centration (5%) the TEWL increases are not signijicantly different
(experiment nos. 1 and 3 - mean?s.e.).

"1 "1
8 "1
Fig. 3. Variation versus time of the improvement of the 4 cosmestic
parameters. This corresponds to the group treated by the emulsion
containing LSA 1% (experiment no. 6).
observed between the two preparations in terms of
the effect on dry skin. No significant effect on
wrinkles was observed with either preparation. In
contrast, significant improvements were noted at six
months in skin firmness, radiance, "healthiness" and
smoothness with the product containing 1% LSA but
not with the excipient (Fig. 3) (Table 2).
Fig. 3 shows the time course, during the 6-month
study period, of the percentage of amelioration in the
different clinical parameters with LSA. A progressive
improvement was obtained, especially in terms of
healthiness (healthy complexion) and radiance (com-
plexion clearness).
Non-invasive characterization: TE WL
(experiments 1 and 3)
Transepidermal water loss was chosen as a represen-
tative index of the keratolytic effect of LSA relative to
the reference compound, salicylic acid. Fig. 4 shows
the results obtained in two experimental situations in
which the two compounds were tested at different
concentrations in the same excipient.
Given the different molecular weights of the two
compounds (264 and 138), we tested them at 1.5%and
0.78%, corresponding to 5.7 mM in both cases. TEWL
was not significantly modified by SA relative to the
excipient, but increased by 15% (pCO.01) with LSA
(Fig. 4). The same figure shows the increases in TEWL
in experiment no. 1, in which the two products were
applied at W/W concentrations of 5% for SA and
1.5% for LSA. Relative to the excipient, the increases
in TEWL were respectively 36% and 31%, not signifi-
cantly different.
Confocal microscopy (experiment no. 2 )
Visualisation of the different layers of the epidermis
by identifying the interfaces between the skin surface
and the horny layer, the horny layer and the living
epidermis, and the living epidermis and the dermis,
allows the thickness of the horny layer and the living
epidermis to be precisely measured. The results in
Table 3 shows that the living epidermis was thickened
by about 20% after 2 and 4 weeks treatment with 1.5%
LSA (p<0.03). The thickness of the SC was not modi-
fied by any treatment.

118
 Lipophilic derivative of salicylic acid and normal skin

TABLE 2. Summary of the statistical results; S refers to the significance of the improvement relative to TO (p<O.Ol)
Improvement after Excipient+LSA 1% Excipient
1 month 4 months 6 months 1 month 4 months 6 months

dry skin S - S S - S
smoothness - - S - - -

firmness - - S - - -

clearness complex - S S - - -

healthy complexion S S S - - -

Replicas (experiment no. 2 )
On the LSA treated zones, desquamation is character-
ized by single cell scaling starting at the first day of
treatment and continuing throughout the first week
(Fig. 5).
Biopsies (experiment no. 4)
The histological aspect of the skin in the control, ex-
cipient-treated and salicylic acid-treated sites were
similar. However, there were subtle differences in the
thickness of the epidermis and the compactness of the
stratum corneum according to the volunteers. The
sites treated with LSA looked different at the level of
the stratum Malpighi, where the keratinocytes ap-
peared smaller and more numerous, and had better
polarity orientation. Fig. 6 shows the thickness of the
stratum corneum in arbitrary units (or the number of
nuclei for the living epidermis). Only the zones
treated with LSA were significantly different (p<O.Ol)
from the other three zones, which were similar.
High-molecular-weight (56 and 64 kDa) cytoker-
atins were present in the upper part of the Malpighian
layer, leaving the germinative compartment unla-
belled. Evaluations by computerized morphometry of
the areas of the Malpighian layer and the germinative
compartment revealed modifications induced by LSA.
These data correlated well with the number of nuclei
per unit area of the epidermis (Fig. 7).
Fig. 8 shows the results obtained with Ki67, which
labels cells in the division phase. A proliferation index
(%) was calculated relative to the number total of cells
in a section of epidermis. This index was significantly
higher in the zones treated with 1.5% LSA than in the
zones treated with 5% SA (pC0.05). These were also
different from the control and excipient-treated zones
( p<0.05).
Discussion
Among the numerous skin care products, moisturiz-
ing preparations have been the subject of many scien-
tific publications showing the efficacy of certain active
substances in skin dryness (6,7). The same holds true
for anti-wrinkle products, even though fewer data
have been published (8,9). The efficacy of sunscreens
is also well documented.
The present study concerns a new compound
having marked effects on aged skin. These effects
essentially involve the radiance aspect, firmness and
softness of the skin.
The results of experiment no. 5 (Fig. 1) show several
cosmetic benefits, which appeared during the first
month of application and increased gradually. This
benefit was noted both by the volunteers themselves
and by the dermatologist. The impact on wrinkles

TABLE 3. Thickness of the stratum corneum and living epidermis,

measured directly in vivo by confocal microscopy
TO T2 T4

SC thickness LSA 1.5% 12.420.6 13.620.6 12.420.4

excipient 12.020.4 13.420.4 12.1?0.6
control 11.820.4 12.520.5 12.3205
epidermal thickn- LSA 1.5% 21.921.3 26.627.7 26.827.9
ess excipient 24.021.6 25.921.6 26.522.3
control 23.522.0 25.622.0 24.421.9

The effects of the excipient and 1.5% LSA were compared to control
values after 2 and 4 weeks of treatment. Only the outlined figures Fig. 5. Aspect of the skin surface 3 days after the beginning of the
are statistically different from those at To @<0.03). treatmen t.

119
LCvCque et al.

Fig. 6. Histomety ofthe epidermis after 4 weeks of treatment with the
different preparations (experiment no. 4). In the 2 graphs, there is no
statistical differences between control, excipient and SA 5%, although
LSA 1% corresponds to a higher number of nuclei (p<O.O1) and to a
thinner SC (p<O.O1) (mean5s.e.).
Fig. 7. Histometry of the epidermis after 4 weeks of treatment with the
different preparations (experiment no. 4). In the 2 graphs, there is no
statistical differences between control, excipient and SA 5%, although
LSA 1% corresponds to thicker malphighian and germinative layers
(p<O.Ol) (mean-+s.e.).

probably resulted from the fact that the volunteers

were asked to assess their fine lines, whereas the der-
matologist evaluated deep wrinkles. These results do
not however reflect the value of the compound pres-
ent in the formulation, as this pilot study was not pla-
cebo-controlled.
In this respect, the results of experiment no. 5 are
extremely important, as they were obtained in com-
parison with the excipient alone, which is an excellent
cosmetic in itself since it contains 5% glycerol. It
should be underlined that this type of experiment as-
sessing the efficacy of a complete product relative to
a moisturizing cream is extremely rare and, to our Fig. 8. Proliferation index (%) of the skin treated by the diferent prod-
knowledge, has never been reported in journals of ucts. LSA treated skin has a higher index than SA treated skin
cosmetic research. Table 2 shows identical positive re- ) SA treated skin has a higher index than control and
( ~ 4 0 5 and
excipient treated zones (p<0.05) (mean5s.e.).
sults for skin dryness with the excipient alone and the
full product; this was to be expected given the pres-
ence of glycerol in both preparations. The presence of
1% LSA in the excipient led to large and statistically effect is more gradual in terms of "healthiness" and
significant improvements in firmness, clearness, radiance, which progressively improved throughout
"healthiness" and smoothness. Fig. 3 shows the time the 6-month treatment period, suggesting a slower,
course of these improvements and indicates that the more profound action, giving a younger aspect to the

120

skin. With regard to smoothness and firmness, the re-
sults appeared more rapidly, reaching 80% of the
maximum at the first measurement one month after
starting the applications.
We then carried out biopsies and noninvasive meas-
urements to determine the mechanisms underlying
these effects on the different layers of the epidermis,
which, after about 4 months, led to a greater cosmetic
benefit than that induced by a simple moisturizing
compound.
In experiment no. 2, we used, for the first time, con-
focal microscopy to determine if treatment with LSA
modified the thickness of the two most important
layers of the epidermis: the the stratum corneum and
the living epidermis (Table 3). Curiously, we found
no decrease in SC thickness, while only the product
containing 1.5% LSA increased the thickness of the
living epidermis by about 21%, as early as the second
week of application (pC0.03).
As explained below, the results on the epidermal
compartment are in keeping with those of experiment
no. 4 (histometry). In contrast, they do not concord
for SC thickness, since histometry suggested that the
SC became thinner. This discrepany will be discussed
later on.
The images obtained by means of scanning micro-
scopy showed that 1.5% LSA induced desquamation
after a few days of treatment. Fig. 5 clearly shows that
this desquamation involved isolated corneocytes and
was thus invisible to the naked eye. This phenomenon
persisted for 7 days application (the lasting of the ob-
servation period). This result may at least partly ex-
plain the improvements in smoothness. Instead of
desquamation of clumps (which leads to a degree of
roughness), LSA led to the loss of individual corneo-
cytes.
One problem in the study of this new compound
was to understand its mode of action relative to sali-
cylic acid. With regard to noninvasive measurements,
keratolytic compounds augment TEWL after a few
days of application (10). This property is classically
interpreted as the consequence of a reduction in the
thickness of the horny layer. To compare the “kerato-
lytic” efficacy of LSA with that of salicylic acid, we
asked the volunteers to use both compounds for two
weeks (experiments 1and 3). In both experiments sali-
cylic acid was applied at 5% and 0.78%, the latter con-
centration corresponding to molar equivalence with
1.5% LSA (5.7 mM). The results in Fig. 4 show that
LSA was 5 to 6X more effective than SA in terms of
TEWL.
Accordingly, we used shave biopsies to compare the
effects on the epidermis of LSA and SA in concen-
Lipophilic derivative of salicylic acid and normal skin
trations at which the increase in TEWL is equivalent
(respectively 1.5 and 5%).
With regard to the morphometry of the living epi-
dermis (number of nuclei) and the stratum corneum,
the results shown in Fig. 5 are highly significant: LSA
led to a reduction of about 21% in the thickness of the
stratum corneum relative to the control zone and the
excipient-treated zone, together with almost the same
percentage increase in epidermal thickness. The re-
sults were highly significant as compared to all the
other zones (p<O.Ol).
These results can be compared with published data
on SA and those on LSA obtained by means of confocal
microscopy. The latter study was not carried out on the
subjects who were biopsied, but on other volunteers
who applied the same treatment. The results are in ex-
cellent agreement for the living epidermis (about a 20%
increase relative to the site treated with the excipient),
but not for the stratum corneum. We have no expla-
nation for this discrepancy, but validation of the con-
focal method relative to classical histometry on the
same subjects remains to be carried out.
In different experimental conditions (6% SA in alco-
hol, 10 days of application) Roberts et al. reported a
clear reduction in the number of SC layers (2-7%).
Apart from the excipient used, the largest difference be-
tween the two experiments lies in the treatment time
and the subjects’ mean age (40 years in our study and
58 years in Roberts’ study). It seems legitimate to con-
sider (as borne out by our measurements of biopsies)
that the effects increase with the degree of hyperkera-
tosis.
Finally, LSA clearly had a more profound effect on
the epidermis, as it markedly increased the thickness
of the germinative layers and the mucous Malpighian
layers. This epidermal stimulation, which is con-
firmed by the Ki67 labelling study (Fig. 8), was bene-
ficial, as it remained within physiological norms. (This
index can reach 4.5 in very young subjects; G. Pierard,
personal result). The latter histological examination
provided insight into the causes of the marked clinical
benefit given by applicaton of LSA in a cosmetic
emulsion. The effect on smoothness was no doubt in-
duced by a regularization of desquamation which, in-
volving isolated cells, was invisible. The natural
roughness of the skin thus tended to diminish. This
effect occurred rapidly. The increase in firmness noted
by the volunteers as early as the first month, in our
opinion, may be interpreted in the light of the thicken-
ing of the living epidermis. Finally, it is difficult to
interpret the other two improvements (radiance and
“healthiness”). These two concepts are effectively
vague and do not correspond to precise physical or
121
LCvCque et al.
even physiological phenomena. Studies based on
measurements of skin color or microcirculation by
means of laser Doppler, for example, should shed
light on this question. The fact that these amelior-
ations were gradual suggests that the overall equilib-
rium of the epidermis is modified, a view supported
by the histometric data at one month of application.
It is logical that an increase in the thickness of the
living epidermis, coupled with a decrease in the thick-
ness of the stratum corneum, would fundamentally
modify the optical properties of the skin (11).
As stated in the Introduction, the use of "keratolytic"
products in skin care is widespread. Recently, the fam-
ily of a-hydroxy acids has been widely applied to skin
care, based on relatively sound data obtained in the
1970s as well as more recent results (which are far
more controversial) suggesting that these compounds
are active against signs of actinic aging (12-14).
To our knowledge, the effects of these compounds
in this setting have not yet been sufficiently docu-
mented.
The compound used in our study is not an a-
hydroxyacid but a lipophilic salicylic acid derivative,
which appears to have properties markedly different
from those of the parent compound. The preliminary
experimental data reported here warrant its use as a
skin care product for the elderly where a stimulation
of the epidermal renewal is desirable.
Acknowledgements
The authors thank Drs. M. Hocquaux and D. Saint-
Leger for their invaluable contribution to the design,
synthesis and selection of this original compound.
References
1. Roberts DL, Marshall R, Marks R. Detection of the action of
salicylic acid on the normal Stratum corneum. Brit J Derma-
to1 1980: 103: 191-196.
122
2. Davies M, Marks R. Studies on the effect of salicylic acid on
normal skin. Brit J Dermatol 1976: 95: 187-192.
3. Huber C, Christophers E. "Keratolytic" effect of salicylic
acid. Arch Dermatol Res 1977: 257: 293-297.
4. Corcuff P, LbvCque JL. In v i m vision of the human skin with
the tandem scanning microscope. Dermatology 1993: 186:
50-54.
5. Corcuff P, Bertrand C, LevCque JL. Morphometry of human
epidermis in-viva by real-time confocal microscopy. Arch
Dermatol Res 1993: 285: 475481.
6. Prall JK, Theiler RF, Bowser PA, Walsh M. The effectiveness
of cosmetic products in alleviating a range of skin dryness
conditions as determined by clinical and instrumental tech-
niques. Int J Cosmet Sci 1986: 8: 159-174.
7. De Rigal J, Losch MJ, Bazin R, Camus C, Sturelle C, De-
scamps V, LbvCque JL. Near infrared spectroscopy. A new
approach to the characterization of dry skin. J SOCCosmet
Chem 1993: 44: 197-209.
8. Meybeck A, Chanteloube F. Cosmetic wrinkle smoothing.
In: Morganti P, Montagna W (eds): A new look at old skin. Int
Ediemme, 1986: 243-259.
9. Corcuff P, Chatenay F, Brun A. Evaluation of anti-wrinkle
effects on humans. Int J Cosmet Sci 1985: 7 117-126.
10. Guillaume JC, De Rigal J, LbvCque JL, Galle P, Touraine R,
Dubertret L. Etude comparee de la perte insensible d'eau et
de la penbtration cutanbe des corticoldes. Dermatologica
1981: 162: 380-390.
11. Agache P, Girardot I, Bernengo JC. Optical properties of the
skin. In: LbvCque JL, ed: Cutaneous investigation in health
and disease. Marcel Dekker, 1989: 241-274.
12. Van Scott E, Yu RJ. Hyper keratinization, corneocytes co-
hesion and a hydroxy acids. J Am Acad Dermatol 1984: 11:
867-879.
13. Lavker RM, Kaidbey K, Leyden JJ. Effect of topical am-
monium lactate on cutaneous atrophy from a potent topical
corticosterold. J Am Acad Dermatol 1992: 26: 535-544.
14. Lavker RM. Topical therapy of aging skin. Am Acad Derma-
tol, Washington DC,December 1993.
Address:
J. L. LtWque
L'OREAL, Centre Charles ZVIAK
90,Rue de General Roguet
92583 Clichy Cedex
France