METHODS FOR IMPROVING UV ABSORBANCE OF SUNSCREEN COMPOUNDS

METHODES POUR ACCROITRE LE POUVOIR ABSORBANT DE COMPOSES ANTISOLAIRES

English Abstract

2137143 9407460 PCTABS00032
Methods for increasing the UV absorbance of certain sunscreen
agents for topical applications yielding compositions exhibiting
improved sun protection factor (SPF) are disclosed. These methods
comprise dissolving or suspending octyl methoxycinnamate or
benzophenone-3 in certain emollient systems, e.g. high polar type
materials such as ethoxylates resulting in a 15% increase in UV
absorbance.

Claims

WO 94/07460 PCT/US92/08215
12
WHAT IS CLAIMED IS:
1. A method for increasing the UV absorbance of octyl
methoxycinnamate which comprises dissolving an effective
amount in an emollient system comprising compounds of the
formula or mixtures thereof:
(I)
<IMG>
wherein R1 is C10-C18 straight or branched chain alkyl, x is
an integer of 5 to 10 and y is an integer of 2 to 6.
<IMG> (II)
wherein R2CO is a pelargonic acid radical
(III)
<IMG>

WO 94/07460 PCT/US92/08215
13
wherein R is an isostearic acid radical and n is an integer
of 2 to 5.
<IMG>
(IV)
wherein R4 is C8 to C12 alkyl, and
<IMG>
(V)
wherein R5CO=COCO and n2 is an integer of 4 to 9, and
(VI)
<IMG>
2. A method according to claim 1 wherein the emollient
system comprises a mixture o PEG-7 glyceryl cocoate :
pentaerythrityl tetrapelargonate a ratio of about 75:25.

WO 94/07460 PCT/US92/08215
14
3. A method according to claim 1 wherein the emollient
system comprises PPG-2-ceteareth-9 : caprylic/capric
triglyceride at a ratio of 50:50.
4. A method according to claim 1 wherein the emollient
system comprises polysorbate 20 : PPG-2-ceteareth-9 :
caprylic/capric triglyceride at a ratio of about 50:25:25.
5. A method according to claim 1 wherein the emollient
system comprises PEG-7-glyceryl cocoate: propylene glycol
isostearate at a ratio of 50:50.
6. A method for increasing the W absorbance of
benzophenone-3 which comprises dissolving an effective
amount of benzophenone-3 in an emollient system comprising
compounds III, IV or VI alone or mixtures thereof.
<IMG> (III)
wherein R is an isostearic acid radical and n is an integer
of 2 to 5.
<IMG> (IV)

WO 94/07460 PCT/US92/08215
wherein R4 is C8 to C12 alkyl, and
<IMG> (VI)
7. A method according to claim 6 wherein the emollient
system comprises PEG-7 glyceryl cocoate : polyglycerol-3
diisostearate at a ratio of 75:25.
8. A method according to claim 6 wherein the emollient
system comprises polysorbate 80 : PPG-5-laureth-5 :
caprylic/capric triglyceride at a ratio of 50:25:25.
9. A composition having an increased UV absorbance of
octyl methoxycinnamate which comprises an effective amount
of said octyl methoxycinnamate in an emollient system
comprising compounds of the formula or mixtures thereof:
<IMG> (I)
wherein R1 is C10-C18 straight or branched chain alkyl, x is
an integer of 5 to 10 and y is an integer of 2 to 6.
<IMG> (II)

WO 94/07460 PCT/US92/08215
16
wherein R2CO is a pelargonic acid radical
<IMG> (III)
wherein R is an isostearic acid radical and n is an integer
of 2 to 5.
<IMG> (IV)
wherein R4 is C8 to C12 alkyl, and
<IMG> (V)
wherein R5CO=COCO and n2 is an integer of 4 to 9.
<IMG> (VI)

WO 94/07460 PCT/US92/08215
17
10. A composition according to claim 9 wherein the
emollient system comprises a mixture of PEG-7 glyceryl
cocoate : pentaerytritol tetrapelargonate a ratio of about
75:25.
11. A composition according to claim 9 wherein the
emollient system comprises PPG-2-ceteareth-9 :
caprylic/capric triglyceride at a ratio of 50:50.
12. A composition according to claim 1 wherein the
emollient system comprises polysorbate 20 : PPG-2-
ceteareth-9 : caprylic/capric triglyceride at a ratio of
about 50:25:25.
13. A composition having an increased UV absorbance of
benzophenone-3 which comprises an effective amount of said
benzophenone-3 in an emollient system comprising compounds
III, IV or VI alone or mixtures thereof.
<IMG> (III)
wherein R is an isostearic acid radical and n is an integer
of 2 to 5.
(IV)
<IMG>

WO 94/07460 PCT/US92/08215
18
wherein R4 is C8 to C12 alkyl, and
<IMG> (VI)
14. A composition according to claim 12 wherein the
emollient system comprises PEG-7 glyceryl cocoate :
polyglycerol-3 diisostearate at a ratio of 75:25.
15. A composition according to claim 12 wherein the
emollient system comprises polysorbate 80 : PPG-5-laureth-5
: caprylic/capric triglyceride at a ratio of 50:25:25.

Description

~ v094/07460 ~ 7~ PCT/US92/08~151- ~
,
.~
. ' ,
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~. `
i :
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
. ! .
1 1 , . .
,::
, .
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'
,