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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 


Al 


(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). 

Published 

With international search report. 



(54) Titie: CHOLESTEROL SULFATE COMPOSITIONS FOR ENHANCEMENT OF STOATUM CORNEUM FUNCTION 



(57) Abstract 

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. 





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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 
sulfate. 

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. 



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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 
therein. 

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 



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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 



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is present in the amounts described above, and the respective 
sunscreens are present in the amounts normally used for UV 
protection. 

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 
about 1.5-7.5%. 

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 
products . 

In all formulations in which cholesterol sulfate is 
employed, it is preferred that the cholesterol sulfate be combined 



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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 



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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- 
limiting examples: 

Example I 

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 



7 



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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 
removal . 

Example II 

The following is a composition according to the present 
invention: 



Material Weight % 

Phase I 

isocetyl alcohol 2.5 

octyl hydroxys tearate 2 . 0 

alpha hydroxylauric acid 0.5 
Phase II 

purified water qS 

eye 1 odext r in 1 . o 

Phase III 

ethoxydiglycol 5.0 

laureth-23 1.5 

dipropylene glycol 1.0 

sodium hyaluronate (1%) 1,2 

pantethine 0 . 1 

PhaselV 

sucrose 2.0 

di hydroxy a c e t one 5 . o 

Phase V 

cyclomethicone 12 . o 

dimethicone 3 . q 

cyclomethicone/dimethicone 2 . 0 

tricaprylyl citrate 1.5 



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dimethicone 3 . o 
Phase VI 

malvaceae extract 0.2 

fragrance 0.4 

tocopheryl acetate 0.1 

wheat bran extract 0.2 

linoleic acid 0.2 

sodium cholesterol sulfate 0.2 

Phase VII 

nylon- 12 2.0 
Phase VIII 

polyquaternium- 3 7 /propylene glycol 1.2 



Example III 

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 



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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 
comeum . 

Example IV 

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 
until absorbed. 

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*) ^ 



10 



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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. 

Example V 

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 
absorbed . 

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. 



11 



^<^«»'^5786 PCr/USOO/02750 



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. 



12 



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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 
thereof . 

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 
imidazole . 

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^^- 
fatty acid. 

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 
cholesterol . 



13 



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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 
sulfate . 



14 



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1/4 



PCT/USOO/02750 




FIG. 1A 




FIG. IB 




FIG. 1C 



SUBSTITUTE SHFFT (QU) f ?fi> 



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FIG. ID 




FIG. IE 




FIG. IF 



wo 00/45786 ^ PCT/USOO/02750 

3/4 



FIG. 2 



a; 

^ 5.0- 
> 

^ 4.5- 

LU 

< 4.0- 
o 3.5- 
U 3.0- 

2.5- 
^2.0H 
J 1.5- 
^ 1.0- 
■2 0 5- 

0.0- 



10% 



1^ 



1 day 



20% 



m 

Wi 



4 day 



PDHA alone 
□ DHA + CS 



25% 



5 day 



SUBSTITUTE <;HFFr rmii P ?f;> 



wo 00/45786 ^ PCT/USOO/02750 

4/4 . 



FIG. 3 



O 



CO 

ro 



4.00-1 
3.50- 

3.00- 
2.50- 
2.00- 
1.50- 
1.00- 
0.50- 
0.00- 



m24 Hour 

□ Day 3 

□ Day 4 

□ Day 7 



DHA ALONE 



DHA, CS AND LIPID 



SUBSTITUTE SHEET fR"i F 



INTERI^jlprONAL SEARCH REPORT 



Inu ^onal AppUeation No 

PCT/US 00/02750 



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 



Category • 



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 
page 5 
claims 

WO 90 01323 A (BERNSTEIN JOEL E) 
22 February 1990 (1990-02-22) 
page 2, line 12 - line 23 



1-12 



-/-- 



1.2,5, 
17,18,21 



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 
riUngdate 

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 
other means 

"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 
inverrtlon 

"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 

09/05/2000 



Name and nrtaiilng address of the ISA 

European Patem Office. P.B, 5018 Patanttaan 2 
NL-2280HVRr|Swijk 
Tel. (*3l-70) 340-204a Tx. 31 651 «po f*. 
Fax: (+31-70) 340-3016 



Authorized officer 



Pel 11 Uablat, B 



f=bon PCTOSAAi 0 (s«3ond ihMl) ( Jiiy 1 002) 



INTERN 



4^)NAL SEARCH REPORT 



iRtfc donoi AppUecUon Mo 

PCT/US 00/02750 



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 
claims 1,2,4 

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" 

XP002I35991 

abstract 

& FRAGRANCE J. (1999), 27(10), 71-74 , 
1999, 

CHEMICAL ABSTRACTS, vol. 104, 
Columbus, Ohio, US; 
abstract no. 10400, 

ABE, TAKASHI ET AL: "Cosmetics containing 

cholesteryl sulfates" 

XP002135992 

abstract 

4 JP 60 161911 A (KANEBO, LTD., JAPAN) 
23 August 1985 (1985-08-23) 



1,2,5,7, 
8,10-12, 
17-21 



1.2,4,5 



1-6, 
17-21 



INTERN^I^NAL SEARCH REPORT ||| 



Infoflnation en patam rimUy memtais 



Inti JlocMl ApplleaMon No 

PCT/US 00/02750 



Patent document 
died in search report 



Publication 
date 



Patent family 
member(s) 



Ptibfication 
date 



DE 19642872 C 



12-02-1998 



AU 4780897 A 
WO 9817244 A 
EP 0941054 A 



MO 9001323 A 



DE 19834812 A 



22-02-1990 



AU 
CA 
US 



4216089 A 
1336762 A 
5508034 A 



15-05-1998 
30-04-1998 

15- 09-1999 

05-03-1990 
22-08-1995 

16- 04-1996 



03-02-2000 



NONE 



JP 60161911 A 



23-08-1985 



JP 
JP 



1433601 C 
62041684 B 



07-04-1988 
04-09-1987 



Fotm PCXnSA/ZlO (pMMt Cmly innu) gUy 1993)