PI^X WORLD INTELLECTUAL PROPERTY ORGANIZ^^N
A A Intemationai Bureau
'INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
(51) International Patent Classification ^ :
A61K 7/48, 7/42
(11) International PublicaUon Number: WO 00/45786
(43) Intemationai Publication Date: 10 August 2000 (10.08.00)
(21) International ApplicaUon Number: PCT/USOO/OZISO
(22i nnemational Filing Date: 2 February 2000 (02.02.00)
(30) Priority Data:
09/246,607 8 Febniary 1999 (08.02.99) US
(71) Applicant: COLOR ACCESS, INC. [US/US]; 7 Corporate
Center Drive, Melville, NY 1 1747 (US).
(72) Inventors: MAES, Daniei, H.; 279A Nassau Road, Huntington,
NY 11743 (US). MARENUS. Kenneth, D.; 62 McCulloch
Drive, Dix Hills, NY 11746 (US). FTHENAKIS, Christina,
G.; 9 Lucille Une, Dix Hills. NY 1 1746 (US).
(74) Agent: TSEVDOS, Estellc, J.; Kenyon & Kenyon, One
Broadway, New York, NY 10004 (US).
(81) Designated States: AE, AL, AM, AT, AU, AZ, BA, SB BG
BR, BY. CA, CH, CN, CR, CU. CZ, DE, DK, Dm' Ee'
ES, FT, GB, GD. GE. GH, GM, MR, HU, ID, IL, IN. IS IP
KE, KG, KP, KR, K2. LC LK, LR, LS, LT. LU, LV. MA*
MD, MG, MK, MN. MW, MX. NO. NZ, PL. PT. RO. RU
SD. SE. SG. SI. SK, SL. TJ, TM, TR, TT, TZ. UA.' UG.'
UZ. VN. YU, ZA, ZW, ARIPO patent (GH. GM, KE. Ls!
MW. SD. SL. SZ. TZ, UG. ZW), Eurasian patent (AM, AZ.
BY, KG. KZ. MD. RU. TJ. TM), European patent (AT. BE,
CH, CY. DE. DK. ES. R. FR. GB. GR. IE, IT. LU. MC.
NL, PT. SE), OAPI patent (BF, BJ. CF. CG. CI, CM. GA,
GN, GW. ML, MR, NE, SN. TD. TG).
With international search report.
(54) Titie: CHOLESTEROL SULFATE COMPOSITIONS FOR ENHANCEMENT OF STOATUM CORNEUM FUNCTION
The present invention provides a method of retarding desquamation of the stratum comeum, and maintaining stratum comeum
thickness, by applying to the skin an effective amount of cholesterol sulfate. The retardation of desquamation can be useful in enhancing
die skin's own UV protection, in prolonging the retention time of a sunless tan, and generally reducing the appearance of lines and wrinkles
associated with both photo- and chronoaging.
reducing the efficacy of this physical barrier and permitting
easier penetration of harmful stimuli such as UV rays. This in
turn leads to UV-damage to the dermal layers of the skin,
resulting in degradation of collagen and elastin, finally
resulting in wrinkling and skin atrophy. Moreover, the thinning
of the stratum corneum can result in a greater visibility of the
wrinkling and atrophy, the cause of which is rooted in the dermis.
Notwithstanding the obvious importance of the stratum
corneum in maintaining a healthy youthful appearance of the skin,
rehabilitation and maintenance of the dermis has been a major
cosmetic focus in preventing the appearance of aging; relatively
little attention has been paid to developing cosmetic means for
maintaining a fairly consistent level of stratum corneum function
into old age. The present invention now provides a means for
retaining this function, and concurrent uses relating to same.
Summary of the Invention
The invention relates to a method of increasing the
thickness and cohesion of the stratum comeum of the skin, which
comprises applying to skin an effective amount of cholesterol
sulfate. The invention also relates to a method of protecting the
skin against UV radiation comprising applying to the skin an
effective amount of cholesterol sulfate. In another embodiment,
application of cholesterol sulfate to the skin reduces
desquamation, and therefore, skin flakiness. In yet another
embodiment, the invention provides a method for enhancing a
sunless tan which comprises applying a self -tanning agent, such as
DHA in combination with an effective amount of cholesterol
Brief Description of the Figures
Figure 1 illustrates the condition of stratum corneum
thickness under different cholesterol sulfate treatment regimens,
as described in Example I: (A) control (no treatment ); (B) 1%
ethanol vehicle control; (C) cholesterol sulfate, O.Ol^g/ml;
(D) cholesterol sulfate, .l^ig/ml; (E) cholesterol sulfate, Ifig/ml;
(F) cholesterol sulfate lOfxg/ml.
Figure 2 illustrates the duration of the self-tanning action
of DHA with and without cholesterol sulfate.
Figure 3 illustrates the duration of the self-tanning action
of DHA with and without cholesterol sulfate and a lipid mix.
Detailed Description of the Invention
The present invention, in its various embodiments, is
predicated on the observation that cholesterol sulfate, when
applied topically to the skin, enhances the cohesion of the
stratum comeum resulting in a more prolonged retention of the
layers of the stratum comeum. Specifically, it has been observed
that application of cholesterol sulfate to skin cells results in a
distinct, dos e- dependent , increase in the thickness of the layers
of the stratum comeum, as shown in Figures IC-F. The observation
is important for a number of different applications; a
particularly significant application is in the maintenance of the
texture of older skin. A current common means of enhancing
smoothness of the skin is to encourage exfoliation. However,
exfoliation necessarily involves a high rate of turnover of the
stratum comeum, and consequent thinning of this layer of the
skin. While not an issue in youthful skin, desquamation in older
skin can, in some cases, simply exacerbate a problem already
established, namely, the natural thinning observed with age.
Thus, application of cholesterol sulfate to retard desquamation
and maintain stratum comeum thickness represents an entirely new
direction in the treatment and maintenance of older, thinning
skin. A thicker stratum comeum aids in preventing or retarding
the appearance of fine lines and wrinkles which so frequently
characterize thinning skin. At the same time, the enhanced
cohesion of the stratum comeum results in an effective
strengthening of the protective lipid barrier naturally provided
To achieve this effect, the cholesterol sulfate or salts
thereof can be applied in any type of cosmetically or
pharmaceutically acceptable vehicle for topical application with
which the active component is compatible, e.g., a gel, a cream, a
lotion, an ointment, a mousse, a spray, a solid stick, a powder, a
suspension, a dispersion, and the like. Preferably, however, the
cholesterol sulfate is not provided in a liposome formulation, and
is formulated in a composition containing relatively low levels of
emulsifiers. Techniques for formulation of various types of
vehicles are well known to those skilled in the art, and can be
found, for example, in Chemistry and Technology of the Cosmetics
and Toiletries Industry, Williams and Schmitt, eds . , Blackie
Academic and Professional, Second Edition, 1996, and Remington's
Pharmaceutical Sciences, 18th Edition, 1990, the contents of which
are incorporated herein by reference. Cholesterol sulfate is
effective in the claimed function when provided in the composition
in an amount of from about 0.05 to about 10%, preferably from
about 0.5 to about 5%, most preferably about 1 to about 3%, all by
weight of the total composition.
The thickening and cohesion of the stratum comeum also
provides other benefits, which, in certain specific applications,
can be appreciated by individuals of all ages . The stratum corneum
represents an important physical barrier between the environment
and the deeper skin layers as well as the internal organs. The
presence of this thicker layer thus will provide a greater level
of protection than is possible with a loose, flaking stratum
comeum. Although this property can be exploited in a number of
ways, perhaps the most important is the enhanced self -protection
from UV rays. The thicker stratum corneum means an increase in
the Minimal Erythemal Dose of UV which will result in sunburn or
more serious skin damage. In connection with this aspect of the
invention, cholesterol sulfate may be beneficially combined with
one or more sunscreens for an enhanced UV protective composition
which provides both short- and long-term protection. Thus, the
invention provides sunscreen compositions comprising effective
amounts of cholesterol sulfate and one or more sunscreens.
Examples of useful sunscreens include, but are not limited to,
inorganic sunscreens such as titanium dioxide, zinc oxide, and
iron oxide; and organic sunscreens, such as camphor derivatives,
cinnamates, salicylates, benzophenones , triazines, PABA
derivatives, diphenylacrylate derivatives, and dibenzoylmethane
derivatives. In such sunscreen compositions, cholesterol sulfate
is present in the amounts described above, and the respective
sunscreens are present in the amounts normally used for UV
An additional use of the cholesterol sulfate is in the
enhancement and prolongation of self -tanning products. One of the
recognized limitations of self -tanners, which are normally based
on dihydroxyacetone (DHA) as the active component, is that the tan
on the skin lasts only as long as the skin cells receiving the DHA
remain in place. In the normal course of events, then, a self-
applied tan usually lasts no more than 5 days, i.e., for as long
as it takes for the stratum corneum layer to which the DHA was
applied to fully turn over. When cholesterol sulfate is combined
with DHA, or any other self -tanning agent, in a typical self-
tanning formulation, however, the rate of turnover of the stratum
corneum to which the composition is applied is slowed down,
thereby permitting a longer rate of retention of the "tanned"
cells, and thus prolonging the length of time the tan remains
visible on the skin. Thus, the invention provides a self -tanning
composition comprising an effective amount of cholesterol sulfate
and an effective amount of a self -tanning agent. In a preferred
embodiment, the self -tanner is DHA, which is usually applied in an
amoxint of from about 2.5 to about 10% by weight of the
formulation. The self-tanner may also be imidazole, preferably in
combination with DHA, in an amount of about 1-10%, preferably
In addition to its use in therapeutic products, cholesterol
sulfate can also be beneficially added to color cosmetic products.
In this regard, effective amounts of cholesterol sulfate are
added to makeup formulations such as foundations, blushes,
lipsticks and glosses, eyeliners, eyeshadows, and the like. A
particular advantage may be obtained with such formulations, in
that the retardation of desquamation may enhance makeup retention
on the skin to which it is applied. The sunscreen/ cholesterol
sulfate combination may also be effectively employed in such
In all formulations in which cholesterol sulfate is
employed, it is preferred that the cholesterol sulfate be combined
with other components of the naturally occurring lipid barrier.
In a particularly preferred embodiment, the cholesterol sulfate is
combined with at least one of each of fatty acids, ceramides, and
a sterol, preferably cholesterol. Fatty acids may be up to 24
carbon atoms in length. Examples of preferred fatty acids include
butyric acid, caproic acid, octanoic acid, decanoic acid,
dodecanoic acid, tetradecanoic acid, palmitic acid, stearic acid,
linoleic acid and oleic acid. Particularly preferred are fatty
acids with a C^^ to C20 chain length.
The ceramides to be employed in the compositions of the
invention are sphingolipids , having a sphingosine or related
molecule backbone with fatty acids or co-esterif ied fatty acids
linked to an amino group on the sphingosine, and in some cases,
with saccharide moieties linked to the terminal hydroxyl of the
sphingosine. In particular, the compositions may contain oo-
esterified ceramides or acylceramides , cerebrosides, (o-esterif ied
cerebrosides, or acylglycosyl sphingolipids. Particularly
preferred types of ceramides for the present compositions are
ceramide III and cerebrosides.
In those compositions in which cholesterol sulfate is
combined with these lipids, the lipid components each can be used
in an amount of from about 0.05 to 10%, preferably 0.5 to about
5%, most preferably about 1 to about 3%, all by weight of the
total composition. In a particularly preferred embodiment, the
cholesterol sulfate and the lipid components are present in
substantially equal amounts in the composition. It will be
understood from the foregoing that the lipid component need not be
pure lipid, but rather may be natural extracts containing one or
more desirable lipids, and used in amounts consistent with
attaining the concentrations recommended above.
The compositions of the invention are applied to the skin in
a manner appropriate to the intended end result. For example, for
the general promotion of the appearance of young, healthy skin by
retardation of desquamation and maintenance of stratum comeum,
the the best results are achieved after regular application over a
period of time. A preferred method of obtaining the benefits of
the composition is via chronic topical application of a safe and
effective amount of a composition containing cholesterol sulfate.
It is suggested as an example that topical application of the
composition, in an amount of from about 0.1 mg/cm^ to 2 mg/cm^ of
skin, be performed from about once per week to about 4 or 5 times
daily, preferably from about 3 times a week to about 3 times
daily, most preferably about once or twice per day. By "chronic"
application, it is meant herein that the period of topical
application may be over the lifetime of the user, preferably for a
period of at least about one month, more preferably from about
three months to about twenty years, more preferably from about six
months to about ten years, more preferably still from about one
year to about five years, thereby resulting in the treatment or
prevention of the external signs of photo- or chronoaging.
When the composition is used in conjunction with a
sunscreen, it is applied in the same amounts as specified above,
on an as -needed basis, to mitigate the effects of exposure to the
sun. When used in combination with a self-tanner, the composition
is also applied in similar amounts, on the portion of the skin to
be tanned, with repetition, again, on an as-needed basis.
The invention is further illustrated by the following non-
This example illustrates the ability of cholesterol sulfate
to retard desquamation and maintain stratum comeum thickness.
Matek skin equivalents are obtained and prepared for use in
accordance with the supplier's protocol. Equilibrated skins are
treated topically with dilutions of cholesterol sulfate.
Cholesterol sulfate is solubilized 1 mg/ml in ethanol, and
serially diluted 10-fold to yield doses of O.Oi, .1, i and
10^g/ml. Each dose is added topically to an equivalent, using a
100^1 volume. Treatment is repeated daily along with media
replacement over a three day period. One sample is treated with 1%
ethanol, representing a vehicle control. Following treatment,
equivalents are fixed according to standard protocol, and sent for
histological preparations. Figtures lA-F show stained sections of
the two controls plus the treatment samples. The figures show a
very loose organization of the stratum corneum in the media
control, with a gradual increase in organization and cohesion of
the stratum corneum seen in the treatment samples, which increases
with the amount of cholesterol sulfate in the treatment. Some
compaction is seen in the ethanol treated sample, which is
believed due to dehydration of the sample combined with lipid
The following is a composition according to the present
Material Weight %
isocetyl alcohol 2.5
octyl hydroxys tearate 2 . 0
alpha hydroxylauric acid 0.5
purified water qS
eye 1 odext r in 1 . o
dipropylene glycol 1.0
sodium hyaluronate (1%) 1,2
pantethine 0 . 1
di hydroxy a c e t one 5 . o
cyclomethicone 12 . o
dimethicone 3 . q
cyclomethicone/dimethicone 2 . 0
tricaprylyl citrate 1.5
dimethicone 3 . o
malvaceae extract 0.2
tocopheryl acetate 0.1
wheat bran extract 0.2
linoleic acid 0.2
sodium cholesterol sulfate 0.2
nylon- 12 2.0
polyquaternium- 3 7 /propylene glycol 1.2
A study is conducted to determine the effect of cholesterol
sulfate on skin flakiness, as an indicator of its effect in
reducing desquamation. Fifteen subjects between the ages of 21
and 65 years are selected for the study. The subjects report for
the study without moisturizers or any other products on their
hands and their baseline measurements are taken. The svibjects are
given a product containing 0 . 5%. cholesterol sulfate in a water and
oil emulsion base to take home and self -administer on their right
hands only, twice a day in the morning after washing cuid in the
evening at least 15 minutes before bedtime for four weeks. The
left hand serves as the untreated control site. The subjects are
only allowed to use the test product and specifically log its use
in a daily diary. At the end of two and four weeks the subjects
return for testing without applying the product for at least 12
hours and they are re-evaluated under the same conditions.
Evaluation of flakiness is determined via the D-Squame Discs
Method and Image Analysis. Briefly, four D-Squame discs are
firmly pressed on the back of each hand with hand held uniform
pressure device and removed by gently pulling away from the skin.
The D-Squame discs are mounted on clear microscope slides and
labeled according to subject's name and visit. Desquamation is
evaluated from the D-Squame discs via the image analyzer. Skin
evaluation is carried out before treatment, and after two and four
weeks of treatment .
An OPTIMA image analyzer is used to evaluate skin flakiness.
The D-Squame samples containing the stratum corneocytes are placed
under a camera on top of a light table and each image is imported
into the image analyzer. The average Gray Value corresponding to
the sample density is measured. The denser the sample, the higher
the Gray Value difference. The treated skin shows a 22.5%
decrease in flakiness relative to baseline after two weeks, and a
24.1% decrease after 4 weeks. The' decrease in flakiness is
apparently due to the observed effect on cohesion of the stratum
This example illustrates the efficacy of the addition of
cholesterol sulfate to DHA in enhancing duration of self -teaming.
Two products are prepared for testing, one a control formulation
containing 5% DHA, and the second the test formulation containing
5% DHA and 0.2% sodium cholesterol sulfate. A total of 10
panelists participate in the study. The control formulation is
applied to the right arm and the test formulation on the other.
Equal amounts of the products (BOOjil) are dispensed and blended in
Color measurements are obtained with a Chromameter before
treatment, 24 hours after treatment, and 4 days and 5 days.
Decrease in reflectance and increase in red coloration and yellow
coloration (AL*, Aa*, Ab*) obtained from the Chromameter are
calculated as compare to baseline skin color. Total color change
AE* is calculated for each time point as follows:
AE*= square root of (AL*) (Aa*) 2+ (Ab*) ^
The results, shown in Figiire 2, demonstrate that there is a
decrease in skin reflectance and an increase in skin redness and
yellow coloration due to the self -tanning effect of the products.
Total change in color values (AE*) observed from the graph show
that there is 10% darker color on the arms treated with the
formulation containing the cholesterol sulfate as compared with
the one treated with DHA alone. After 4 and 5 days, there is
still 20% and 25% darker tan on the site treated with DHA and
cholesterol sulfate, as compared with the site treated with DHA
alone. These data show that the addition of cholesterol sulfate
to DHA results in a longer lasting tan.
This example illustrates the efficacy of a composition
containing DHA combined with cholesterol sulfate and a lipid mix
in enhancing the intensity and duration of self -tanning.
Two products are tested: a test product containing 5% DHA, 0.2%
sodium cholesterol sulfate, 0.2% linoleic acid and 0.2% SC
complex, containing wheat bran extract and olive oil extract, and
a standard self -tanning product containing only 5% DHA as control.
A total of 22 panelists participate in the study, divided
into two groups of eleven each. The control is applied on the
right arm, and the test product is applied on the left arm. Equal
amounts of the product (SOOjil) are dispensed and blended in until
Color measurements are taken as described in Example IV. The
results, shown in Figure 3, demonstrate that there is a decrease
in skin reflectance and an increase in skin redness and yellow
coloration due to the self -tanning effect of the products. The 5%
DHA product with the lipid mix appears to retain color more
efficiently during the entire seven-day study period when compared
with the control product.
What is claimed is:
1. A method of retarding desquamation in the stratum corneum of
the skin comprising applying to the skin a composition comprising
an effective amount of cholesterol sulfate.
2. The method of claim 1 in which the composition comprises from
about 0.05% to about 10% cholesterol sulfate.
3. The method of claim 1 in which the composition comprises about
1% to about 3% cholesterol sulfate.
4. A method of treating or preventing the thinning of the stratum
corneum of the skin comprising applying to the skin a composition
comprising an effective amount of cholesterol sulfate.
5. The method of claim 4 in which the composition comprises from
about 0.05% to about 10% cholesterol sulfate.
6. The method of claim 4 in which the composition comprises about
1% to about 3% cholesterol sulfate.
7. A method of protecting the skin from the effects of UV
radiation which comprises applying to the skin a composition
comprising effective amount of cholesterol sulfate.
8. The method of claim 7 in which the composition comprises from
about 0.05% to about 10% cholesterol sulfate.
9. The method of claim 7 in which the composition comprises about
1% to about 3% cholesterol sulfate.
10. The method of claim 7 in which cholesterol sulfate is applied
in combination with at least one sunscreen.
11. A composition for protection of the skin from the effects of
UV radiation comprising an effective amount of cholesterol sulfate
and at least one sunscreen.
12. The composition of claim 11 in which the sunscreen is
selected from the group consisting of titanium dioxide, zinc
oxide, iron oxide, camphor derivatives, cinnamates, salicylates,
benzophenones, triazines, PABA derivatives, diphenylacrylate
derivatives, dibenzoylmethane derivatives, and combinations
13. A method for artificially tanning the skin comprising
applying to the skin a composition comprising applying to the skin
an effective amount of cholesterol sulfate and an effective amount
of at least one self -tanning agent.
14. A composition for artificially tanning the skin comprising an
effective amount of cholesterol sulfate and an effective amount of
at least one self -tanning agent.
15. The composition of claim 14 which comprises DHA as the self-
tanning agent .
16. The composition of claim 15, which also contains an
17. A composition for retarding desquamation and enhancing the
thickness of the stratum corneum comprising an effective amount of
cholesterol sulfate and effective amounts of at least one of each
of fatty acids, ceramides and a sterol.
18. The composition of claim 17 in which the fatty acid is a C^^-
19. The composition of claim 17 in which the ceramide is ceramide
III or a cerebroside.
20. The composition of claim 17 which comprises cholesterol
sulfate, a C^^-C^o fatty acid, ceramide III or a cerebroside, and
21. A method of preventing or retarding the appearance on the
skin of fine lines and wrinkles associated with aging which
comprises applying to the skin an effective amount of cholesterol
SUBSTITUTE SHFFT (QU) f ?fi>
wo 00/45786 ^ PCT/USOO/02750
■2 0 5-
□ DHA + CS
SUBSTITUTE <;HFFr rmii P ?f;>
wo 00/45786 ^ PCT/USOO/02750
□ Day 3
□ Day 4
□ Day 7
DHA, CS AND LIPID
SUBSTITUTE SHEET fR"i F
INTERI^jlprONAL SEARCH REPORT
Inu ^onal AppUeation No
A. CLASSIFICATION OF SUBJECT MATTER
IPC 7 A61K7/48 A61K7/42
According to imamational Patem Classrfication (IPC) or to both nationai das stfteation and IPC
B. FIELDS SEARCHED
Miramum documentation searcnod (dassrficaiwn system toUowed by ctasadtcaiion svrrtMiai
IPC 7 A61K
Oocumeniation s«arch«d omor than minimum documemaUon to the extern that such documams
are inctudad in the fields searched
Betfroroc data base consuBed dunng the mtemationaJ search (name of data base and. whafo practical,
search terms used)
C. DOCUMENTS CONSIDERED TO BE RELEVANT
Citation of document with indication, where appropriate, of the relevant passages
Relevant to datm No.
DE 196 42 872 C (HENKEL KGAA)
12 February 1998 (1998-02-12)
page 3, 1 ine 13
page 5, line 12 - line 23
WO 90 01323 A (BERNSTEIN JOEL E)
22 February 1990 (1990-02-22)
page 2, line 12 - line 23
j X) ^'^'Wier documents are listed in the continuation of box C.
* Special categories of cited documents :
Patent family members are listed in annex.
"A" document deflnirtg the general state of the art which is not
considered to t>e of partlcutar relevance
^ eoilier document but published on or after the ^emational
T-* document which may throw docijts on priority claim(s) or
which is cited to establish the publication date of another
citatton or other special reason (as specified)
"O* document rslomng to an oral disclosure, use. exhttition or
"P* document pubttshed prior to the intemational fitoM date but
later than the prionty date ctatmed
"T later document piAfished after the intemational fOing date
or priority date and not in conflict with the app&cation but
citod to understand the princfile or theory undertytng the
"X" docun)«rt of partkaiar relevance: the ctaimad nvention
cannot be considered novel or cannot be considered to
nvohre an inventhn step when the document is taken aione
"Y' ^5^^"^ particular relevance: the claimed Invention
cannol be consktored to involve an inventive step when the
documert is combined wrth one or more other such docu-
menta, such combination being obvious to a person skilled
tn the ait.
doojmeni member of the same patent famiy
Data of the actual completion of the tntemattonal search
19 April 2000
Oats o( mailing of ttw intamational saarcn rapoct
Name and nrtaiilng address of the ISA
European Patem Office. P.B, 5018 Patanttaan 2
Tel. (*3l-70) 340-204a Tx. 31 651 «po f*.
Fax: (+31-70) 340-3016
Pel 11 Uablat, B
f=bon PCTOSAAi 0 (s«3ond ihMl) ( Jiiy 1 002)
4^)NAL SEARCH REPORT
iRtfc donoi AppUecUon Mo
C^Contlnustlon) OCXUMENTS CONSfOERED TO BE RELEVANT
Category ' Citation of documant. with irKlication.wnero appropnate. ot the relevant passages
Relevant to daun No.
DE 198 34 812 A (BEIERSDORF AG)
3 February 2000 (2000-02-03)
page 3, line 27
page 3, line 40 - line 44
page 3, line 61
page 6, line 30 - line 37
page 7, line 4,5
page 7; example 2
page 9, 1 ine 9
CHEMICAL ABSTRACTS, vol. 132,
Columbus, Ohio, US;
abstract no. 170820,
WILDEN, WIM VAN OER ET AL: "A
skin-identical lipid concentrate for an
improved skin-barrier function"
& FRAGRANCE J. (1999), 27(10), 71-74 ,
CHEMICAL ABSTRACTS, vol. 104,
Columbus, Ohio, US;
abstract no. 10400,
ABE, TAKASHI ET AL: "Cosmetics containing
4 JP 60 161911 A (KANEBO, LTD., JAPAN)
23 August 1985 (1985-08-23)
INTERN^I^NAL SEARCH REPORT |||
Infoflnation en patam rimUy memtais
Inti JlocMl ApplleaMon No
died in search report
DE 19642872 C
AU 4780897 A
WO 9817244 A
EP 0941054 A
MO 9001323 A
DE 19834812 A
JP 60161911 A
Fotm PCXnSA/ZlO (pMMt Cmly innu) gUy 1993)