Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
~ v094/07460 ~ 7~ PCT/US92/08~151- ~
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.~
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8 P ~ C I F I ~ A T I O N~
:~ET~ODB ~OR I~PROVIN~ ~V A~80RB~NC~ OF:8~N8CREEN C0~PO~8
;r
:~ : o which the following is a specification: ~
, ,
!:
. Fiel~ of t~e ~nv~ntion :~ ~
:~ ~ . , ;,,The present invention rela~es to methods ~or~ :
increasing the W absorbance of~certain sunscreen agents
fQr topical appl;ications yielding compositions exhibiting
:~ 5 improved sun protection factor~: (SPF). ~hese: methods
; ~ .co~prise dissoIving or~suspending octyI methoxycinnamate or ~ .
benæophenone-3 in certain emollient syst~mi resl~ltlng in a
l5%.increase 1n1 W~absorbance.
2. Dac~roun~ o~ tbc In-cntio~
: 10The sun emits energy in a continuous band throughout .
` the ~lectromagneti~c:~spectru~ which includ~s the ultraviol:et
range (200-400 nm),~that~part of ~he spectrum that tans and
: ~ burns the skin.~ : Prolonged exposure~of a person'~ skin to
2~ 37~3 ~
W094/~7460 PCT/US9~/08~
. .
the ~unlight may cause a variety of conditions. For
example, ~t can cause premature aging of the skin. In ~ome
cases, it may cau~e the development of skin cancers such as
basaI cell cancer, ~quamous cell cancer and melanoma. See
or example, Blum, H. F. nSunl.ight As An Environmental
Factor in Cancer of the Skin~. Military Mediclne, 117:
202, 1955; Consequently, many products or measures have
been marketed to protect the skin from the harmful e~fects
of excessive exposure to the ~un. Sunscreen agent~ such as
octyl methoxycinnamate and benzophenone-3 hav~ gained wide
ac~eptance. The5e agents act by a~sorbing W light thereby
offering the selective protection against the harmfùl
effect~ of W wave band5. In use, the compounds are
dissolved or suspended in ~olvent systems such as ethanol,
isopropanol, propylene glycol, and mineral oil, and the
resulting compositions applied to the skin.
3. De~criF~ion of th~ Relate~ Art
nEncyclopedia of W ~bsorbers for sunscreen Products"
in Cosmetics and ~oile~ries, vol. 201, March 1987 authored
by Dr. N. Shaath and published by Allured Publishing Corp.
describes benzophenone-3 as well as octyl methoxycinnamate
as sunscreen agents. Under the monograph of each of these
: compounds, there are among others a description of their W
properti~s. These monographs are incorporated herein by
reference. The UV properties are datermined by measuring
: the wavelength of ~maximum a~:sorption ( ~ max3 in the
appropriate ~ solvents ~ ethyl alcohol (EA) or mineral oil
(MO) ~ . It .is ~recorded, along wlth the ms;~lar extln tion
aoef~icient or moIar absorptivity (~) and the K Value.
For benzophenone-3, the W properties are~
~ ~ max (EA~: 288/325~ ~nm max(MD~: 288/329 nm
.
14,000/9,400 ~c: 4 . 67 mg/L in EA) ` 1 ;
17,700/7,800 (c: 4.00 mg/L~in ~0)
: R Value~(E~): 41~ ~
:
~137~
"ViO94/0746~ PCT/US92/08215
3 ..
and~or octyl methoxycinnamate the W propertie~ are: '
max (EA): 311 nm ~ ax(M0): 289 nm
iE 23,300 (c~ 7 mg/L in EA)
19,7Qo (c: 10.24 mg/L in M0)
S K Value (EA): 84 .
There are several patents discloslng the use o~
various sunscreen agentis. For example, U.S.. patent
4,940,577 issued July 10, 1990 discloses a wat~r-in~oil `
emulision contalning ~s a sunscreen agent compounds such as
octyl dimethyl PABA, octyl methoxycinnamate, benzophenone~ ~;
3, octyl salicylate and mixtures thereof. Qther patentis, `~`
e.g. U.S. patents ~,940,574, 4,919,934,~ 4,89~4,22~, `
~,869,897, 4,851,434 and 4,847,072 disclose the use of
~benzophenone~3 and others as suniscreen agents.
U.S. patents 5,075,333 and 5,061,733 discloses the use
of Cetiol LC (caprylic/capric acid/coco :ester) and Cetiol
V (decyl oleate) in creams and gelsO
.,:
. ~umma ~ o~ t~a Invention
In accordance with this invention, we provide a method
: 20 whereby there is a significant increase in absorbance for
octyl methoxycinnamate and benzophenone-3 with no
significant shi~t in:wavelength of maximum absorbal~ce. In
; general,~we pro~ide a method whereby there is a minimum of
lS% increase in absorbance of these:compounds.
1!~. i 25 ~ I Bro;~dly:æpeaking, we have found that~:the UV:ab~rbance
of octyl methoxycinnamate is significantly increased when
it is dissolYed or suspended in certain highly polar~type
materials, i.e. ethoxylates and more partlcularly the
: following compounds: I, II, III, IV, V and VI.
.
:
.
21~7 1 ~3
WO 94/07460 P~/US92/082~
f `. :^
. Rl - O ( C~H~O ) x ( H2C\ ~ CH - CH~ ) rH ( I )
O ' :
wherein R1 i~ C1o-C1~ E;traight or branched chain alkyl, x i5 . .1
an in~eger of S to lO and y is an integer of 2 to 6.
:
1 1 '
O - C ~ ~2 ,
O CH2: C) ~.
R2 -- C- O - CH2 ~- C ~ - ~CH20 - C -~
~ 1H : :
.10 O - C ~
~ J l
~: o
~ . .
wherein RCO is a pelargonic acid radical ~ ~ ~
,,
R~l~ t CH,-CH-CH2-O-~ n ~C-R ( III )
15; . ~ : lH
wherein ~ is an isostearic acid ~rad~ical and~ n is an Integer~
o~ 2 to 5.
f o ~ R~ (IV)
, ~ , .
~C - o - a ~
~ 094/07460 2 ~ 3 7 1 ~ 3 PCT/US9~/0821;
whe~ein R~ is C8 to C12 alkyl, and
O ,, !:
11 '~
_ C - O~C2H/,O~n2 - C ~ (V~ `, ,i
- C - OH
S _:C - OH
t `
where.in R5CO=COCO and n2 is an integer of 4 to 9, and
O ,
CH3(CH2)16-C-OCHz-CHOH (YI)
~H3 .. ~;
,;
lOFor benzophenone-3, the W absorbance is significantly
increased when it is dissolved or suspended in solvents
III, IV and VI or mixtures thereof. ~ l
In an abbreviated SPF tes~, we have found that the .~;
novel system described herein e~hibits signif icant
increases in SPF when compared to the sy~tem using mineral
,....
~il .
: SPF as used herein means the test used by the FDA
which is essentially the ratio ~of;the amount of anergy .
required to produce a minimum erythemal dose (MED) to the
; 20amount of energy to producei the :same MED without any~
treatmant by the product.
S. DQt~ilsd Descr~ptio~ of the Invent~o~ :
: The present invention is;directed to a method ~and ,
means whereby thère is an increase in UV light abs~rbance ~:
with no signi~îcan~ shift in wavelength o~ :maximum
~: ~ absorbance :for the known: sun~creen~ :agents,~ octyl : t ~ `~
~methoxycinnama~ie:and benzophenone-3. The present invention
: also includes ;within~ i~s~scope compositiong comprising
.
.
:~: : .
2~37~3 ~;
W0~4/07460 PCT/US92/08~. `
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t~ese compounds exhibiting not only enhanced W absorbance
but.also have emollient properties for topical appl~cation.
The method of ~he present invention comprlse~ mixing
together an effective ~unscreen amount of ~ octyl
S methoxycinnamate and benzophenone-3 in the ~elected system,
i.~. the compound6 identified as I to VI a~ove either al~ne
or as a blend a5 a binary or tertiary system. The result~
are tabulated in Table~ I and II.
.
T~BL~
OCTY~ ~T~O~YCINN~MATB
~olv ~t avelenqth ~.~ t Ab~orha~ce
Cha~q~
IPA 309.0 0.34S - `
, `
Mineral Oil 291.5 0.360 +4.3 .:
.:
PE~-7 Glyceryl 3lQ.0 0.458 +32.8 ~ :
Cocoate
~ Caprylic/Capric 308.0 0.405 +17.4
:~ Triglyceride
: . ::
PPG-2-Ceteareth-9 310.0 0.444 +28.6
Caprate
.
:~ ~sopropyl ~yristate 30~.0 0.371+ 7.5
:
: : Octyl Stearate 307.0 0.310-10.1
exyl Laurate 307.0 ~ ` 0.3531 + ~-3 ,,
: `
.
.:
.
~ ~ .
: :
:
.
9UB~TiTUTE SHEEr
~ ~,
21371d3
~ 094/07460 PCT/US92/0821~ t.
: f
TABLB II
; B~NZOP~BNo~-3
801~e~t ~nvelen~th ~ ~b~orbance.
~h~q~ ,
IPA 323.0 0.204 - . -
Mineral Oil 327.0 0.172 -15.7
PEG-7 Glyceryl 32305 0.243 +l9.1
Cocoate
~
Caprylic/Capric 328.0 0.205 + 0.5
Tr~ 91 yceri de ~ :
~;
PPG-2-Ceteareth-9 323.0 o.241 +18.1
Capl ate
..
Coco Caprylate/ 3~6.5 . 0.179 ~ -12.3
Caprate
Octyl St~arate 328.5 0.191 - 6.4
~exyl Laurate 327.0 0.197 - 3 . 4
~5
The above results are obtained by combining the
selected sunscreen agent at ab~u~ ~500 ppm in the system as
described. :The above results also demonstrate the
surprising e~ect of the present invention~as not all polar
compounds have the positive influence in increasing W ~ -
; absorbance. ,
Examples of commercially a~ailable solYen~s which fall ,
:~ ~ within I are PPG-5-laureth-5 and PPG-2-ceteareth 9; those ,~
which fall wit~in I I include ~ pentae~ythrityl .
j
tetrapelargonate; those which fall with~ III include ,~
polyglyc~rol-3: diisos~eara~e; ~ose whi~h fall wi~hin IV
include caprylic/capric tri~lyceride a~d thosa which ~aIl~ .
within ~ include PEG-7-glyceryl cocoate and those which : .
fall within VI include propylene glycoI isostearate,
: ~
: ~ SUB~ U~E SHEEr:
2 ~ 3 71 ~ 3
W094/07460 PCT/US92tO82
For octyl methoxycinnamate the combination of PEG-7-
glyceryl cocoate wi~h pentaerytritol tetrapelargonate at an
approximate ratio of about 75:25, a combination of PPG-2-
ceteareth-9 : caprylic!caprlc triglyceride at an
approximate ~0:50 and a combination of polysorbate 20 :
PPG-2-ceteareth-g : caprylic~capric triglyceride at an
approximate rat~o of about 50:25:25 and glycerol cocoate:
propylene glycol i~ostearate at an approximate ratio of
50:50 is advantageous a~ the result~ng composition exhibits
a 20% inc~Qase in W ab~orbanc~. For benzop~enone-3, a
combination of PEG-7-glyceryl cocoate~: polyglycerol-3
diisostearate at an approximate ratio of 75:25 and a
combination of polysorbate 80 : PPG-5-laureth-5 :
caprylic/capric triglyceride at an approximate ratio of
S0:25:25 is advantageous as these exhibit a 20% increase in
W absorbance.
As thosa s~illed in the art would appreciate for
topical applicàtions, s~nscreen composition must be non-
to~ic and non-irritating to the skin and capable o
application to the s~in as a uniform Gontinuous film, i.e.
an emollient effect. ~In addition, the active sunscreen
affects must rem~in chemically stable in the vehicle for
topical appllcation.~ The; compositions of sunscreen agents
prepared ~in àccordance with the present exhibit these
desirable properti~es i;n addition to enh~nced W absorbance.
In an abbre~iated`~;SPF test~ involving ~ive people per
sunsareen agents,~there ~was a signi~icant lncrease ~in SPF
-~ ~ when compared to`the;same agent dissolved in mineral oil.
In a commercial embodiment of the present invention,
i `Ithe system may~include other age~s traditionally used ~ln
formulating sunscreen products. These agents include for
example preservat~ives (such as~methyl and~propy}~ paraben)~
fragrance, anti-oxidants,- ~wetting agents, emulslfiers,
emulsion stabilizers and t~e like.
In order~to fur~her;illustrate the practice~of the
invention, tha~following e~amples a~re ;included:
~094/07460 ~13 7~!~ 3 PCT/U592/08215 D
~xamplo 1 ! -`
Emulsions were prepared a~ follows:
t% W~W~
Inaredien~ 1 ~ 3 4
:, :
EAB~_~
Stearic Acid 5.~00 5.00 5.00 5.00 5.00
methoxycinnamate) 7~50 7.50 7.50 7.50 o ; i~
!"`'
(Benzophenone-3) ~ 3.00 ~ 3.0: 3.00 3.00 3.00~
, . .
Min~ral Oil :~ 10.00 ~ ,`t`
: PEG-7 glyceryl cocoate - 5~00 5.00 7.50 - -
. .
Pentaerythrityl
tetrapelargonate - 5.00 - - .50
Propylene glycol - : - 5.00 ~ -
isostearate
` Poly~lycerol-3 2.50 :
dt.isostearate
~ 20 Water 51.~80 ~ 51.80 51.80~ 51.80 51.80
:~; : 2%~Carbopol 941 ~20.00 20.0020.00~ 20.00~ 20.00
Triethanolamin2 2.45 2.452.45 2~45 2.45
:
Glydant ~: ~` 0.25 0.25~0.25 0.2~ 0.25 ~ ,
`~ 25 (antioxidant) : : ,
TO~AL I :~ 100.00 100.00:100.00 100l.00 1l00.00
21371q'~
WOg4/07460 PCT/US92/08~
Example 1 ~cont.)
;
(% W~W~
Inqredient 6 7 ~ 9 -
PART A
Stearic Acid ~ 5.00 S.OO 5.00 5.00
Parsol MCX (Octyl~
methoxycinnamate) ~7.50 7.50 7.50
E~Banolph67one-3) ~ 3.00 3.00: :3.00 3.00
10PPG-5-laureth-5 :5.00: 2.50
Capryl c Capric ~ 5.00 5. 0O 2. 50
PPG-2-ceteareth-9 ~ ~ - S.OO - 2.50
Polysorbate 80 ~ 5~ ~0 _
15~ Polysorbate 20 ~ 5,00 ~ ;~
Water: ;~ 51.80~51.;80 :;~ 51.80 51.~80
2%~;:Carbopol 941~ 20.~00~ 2~0.00~20~00 20.00
Trie~ha~nolamine~ 2.45 ~ 2.45 ~2.45 ~ ~2.45
0 ~ ` PA~T~ C :
: : Glydant . ~ 0.25~ 0.25 0.25 ~ 0.25
antioxidant)
TOTAL~ 100.00~00.00~ ~loO.OO 100~.00
~1371~3
O94/~74~0 PCT/~S92/08215
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1 1 , . .
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2x~mpl~ 2
The SPF val~e~ of various emulsions which contain
ben~ophenone-3 and octyl methoxycinnamate were as follows:
SPF ': ':
5 EQ~bl3~iÇn Emollien~ Sys~e~ ValUe
1 Mineral Oil 10.7
(as a control) ~ .
2 PEG-7 glyceryl cocoate: -
pentaerythrityl tetrapelargonate (50:50) 13.2
3 PEG-7 glyceryl cocoate::
propylenc glycol ~sostearate ~50:50) 13~2 .
4 PEG-7 ylyceryl cocoate:
polyglycerol-3 diisostearate (75:25) ~.2
pentaerythrityl tetrapelargonate: ' ;:
polyglycerol-3 diisostearate ~75:253 11.6 :~.
.
6 PPG-5-laureth-5: `~
caprylic/capric triglyceride (50:50) 13.5 .
7 PP~-2-ceteareth-9~
caprylic/capric triglyceride (50:50) 16.5
ao 8 ~olysorbate;20 : PPG-5-laureth-5: I.
caprylic/capric triglyceride (50:25:25) 13.8
9 Polysorbate 80 : PPG-2-cete~reth-9;
caprylic/capric triglyceride (50:25:25) 10.5 ~ :
,;;,
t'
,