Note: Descriptions are shown in the official language in which they were submitted.
~ 107~
B~CXGROllND OF TIIE INVENTION
The present invention relates to cosmetic compositions
comprising select conjugated dienes, which, when topically
applied to animal, including human, skin provide protection
from the chronic effects of prolonged exposure to sunlight.
A variety of physiological responses to ultraviolet
radiation have been observed, and various methods of con-
trolling the harmful responses have been provided. The most
well recogniæed responses include, for example, immediate
responses such as the generation of erythema (sunburn)
followed by reversible pigmentation or melanization, and
chronic responses such as wrinkling, creasing, and carcinoma
of the skin. In general, it is believed that both immediate
and chronic responses occur as a consequence of varying
~- degrees of exposure to ultraviolet radiation in the range of
2950A to 4000 A. Within this range, ultraviolet radiation
is able to penetrate the outer protective layers of the skin.
:', . :
'`~ 20
, ... .
' -:
'
~ .,'
~''.' :
. ' ' .
,
.'',
. ..
~ 7(~4~
One means of controlling undesirable responses
to ultraviolet radiation is to avoid exposure to sunlight
for more than short periods of time. However, most people
enjoy outdoor recreation and admire melanization of the
skin. Moreover, some degree of insolation is desLrable
to insure adequate Vitamin D synthesis. Accordingly,
previous research has focused on methods of control?ing
the more immediate erythemogenic responses, thus enabling
people to enjoy exposure without undue discomfort or
irritation. Commercially available "suntanning" prepara-
tions mitigate the dosage of erythemogenic radiation
; which penetrates the outer skin thereby allowing the
. ~
tanning response while preventing severe erythema. A
wide variety of ultraviolet reflecting and absorbing
is agents are known and disclosed in the prior art~
Although suntanning preparations enable people
~, to enjoy outdoor activities without discomfort, such prep-
arations also mute the natural warning system which calls
. ': .
- attention to the prospect o~ c~ronic damage. As a -
consequence of the prolonged periods of exposure, encouraged
by reduced erythemogenic response, absorbed ultraviolet
radiation is believed to cause chronic changes in the
epidermis. Hyperkeratinization, which constitutes the
major natural defense to prolonged exposure, increased
marking of the skin; areas of pigmentation and atrophy;
superficial scaling and telangiectasls or tumorous swelling
~ ~ .
.
.:', :
.` ' ~
-- 2 --
. ' .
~7~24~
of the small blood vessels constitute some of the visible. ~
signs of chronic damage. The development of skin cancer or ~ ~.
pre-cancerous lesions (actinic keratoses) is also known to
be induced by extensive exposure to erythemogenic radiation.
Accordingly, while known compositions comprising
sunscreening and ultraviole~ radiation absorbing agents
provide relief from the more immediate erythemogenic response,
. the chronic effects of prolonged exposure to sunlight remain
~.
substantially unaffected.
5UMMARY OF THE INVENTION
The present invention provides cosmetic compositions
.~ which, when topically applied, provide substantially complete .
relief from the chronic effects of exposure to sunlight,
comprising a select con~ugated diene in combination with a .
. ~
topical pharmaceutically acceptable surfactant containing
vehicle. Thus, the present invention in its broadest aspect
relates to a composition adapted for topical application and :
. capable of inhibiting chronic damage to skin induced by ultra-
violet radiation in the range of 2,950 A to 4000 A, comprising
an effective ultraviolet absorbing amount from about 0.001%
to about 25~, by weight, of a conjugated diene~est`er or amide
having an acid portion derived from p-methoxy cinnamic acid,
; p-aminobenzoic acid, salicylic acid, or p-dimethyl amino
benzoic acid, and an alcohol portion derived from: .
, ~ .
2,4-hexadien-1-ol~ .
3,5-heptadien-1-ol,
. 3,5-octadien-1,8-diol, . .
.: ~
.~ 3-me~hylene-4-penten-1-ol,
~: 3-ethylidene-4-hexen-1-ol,
6,7-bis(l-hydroxy-2-ethyl)-5,7-dodecadiene,
3-(1-hydroxy-2-ethyl)-1,8-dihydroxy-3,5-octadiene,
- 3 - ~:
:' ,
24~ ~ ~
9,11-dodecadien-1-ol,
octa-5,7-dien-1,2-diol,
4,6-heptadien-2-ol, :~
2,9-dihydroxy-2-methyl-4,6-nonadiene,
2,9-dihydroxy-4,6-decadiene,
5-hydroxymethyl-1,3-cyclohexadiene,
2-(1-hydroxy-2-ethy})-1,3-cyclohexadiene,
2,3-bis(l-hydroxy-2-ethyl)-1,3-cyclohexadiene,
. . ~
2-~1-hydroxy-2-ethyl)-1,4-dimethyl-3-butyl-1,3-cyclo-
hexadiene,
:. l-(l~hydroxy-2-ethyl)-1,3-cycloheptadiene, ~:
. .2-(1-hydroxy-2-ethyl)-1,3-cycloheptadiene, : - :
: 2,6-bis(l-hydroxy-2-ethyl)~1,3-cycloheptadiene/
6-~1-hydroxy-2-ethyl)-1,3-cycloheptadiene,
(l-hydroxy-2-ethyl)-cyclonona-1,3-diene, : :
: 7-hydroxy-1,3-cyclononadiene,
;~. 7-(1-hydroxy-2-ethyl)-1,3-cyclononadiene
l-(l-hydroxy-2-ethyl)-1,3-cyclotetradecadiene,
, 2-(1-hydroxy-2-ethyl)- ~1(2)'8-hexalin,
::~ 20 ~1(2)~8-6-hexalol~ or
. 1,17-bis cyclohexene-4-ol; .
or an amine portion derived from~
2,4-hexadiene-1-amine, :
1,6-diamino-2,4-hexadiene, :~
~:~ 2-lower alkyl amino-1,3-butadiene,
-~ l-amino-3,5-heptadiene,
l-amino-3,5-hexadiene,
1,8-diamino-3,5-octadiene, . :-: :
: " ~ .
` 3-methylene-4-hexene-1-amine, : :
.. 30 3-(1-amino-2-ethyl)-2,4-hexadiene, :~
: ,
-~ l-amino-4,6-dodecadiene,
' h~, ,:
,
.' ~' ~ '~di
: ~
~ "
l-di lower alkyl amino-3,5-hexadiene,
l,9-bis(di-lower alkyl ami.no)-4,6-nonadiene,
l-di-methyl amino-3-methylene-4-hexene, ~
l-N-phenyl-N-lower alkyl amino-3,5-hexadiene, ~ :
l~N-piperidino-3,5-hexadiene,
l-lower alkyl amino-3,5-heptadiene,
1,2-dihydropyridine,
3-vinyl-1,2,5,6-tetrahydropyridine,
2,7-dihydroazepine,
2,3,8,9-tetrahydroazonine,
; 4-(I-hydroxy-3-butenyl)-1,2,5,6-tetrahydropyridine, .
2,3,8,9-tetrahydro-N-lower alkyl azonine, r
2-amino-1-ethyl)-1,3-cyclononadiene,
2-(2-amino-1-ethyl)-1,3-cyclononadiene,
: 1-(2-di-lower alkyl amino-1-ethyl)-1,3-cyclononadiene,
- 1,4-bis(2-di-methyl amino-1-ethyl)-1,3-cyclononadiene,
. or
1-(2-piperidino-1-ethyl)-1,3-cyclononadiene,
in a skin compatible vehicle containing from about 0.1% to
about 10%, by weight, surfactant wherein the surfactant is a
nonionic, cationic or amphoteric surfactant or from about ~.
0.01% to about 0.5%, by weight, of a non-soap anionic sur-
factant.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
,, I :
The essence of the instant invention resides in the
discovery that certain con~ugated dienes, more thoroughly
described hereinafter, when topically applied prevent the
undesirable chronic effects of prolonged exposure to sunlight.
Cosmetic compositions comprising these conjugated dienes
30 can be topically applied :~
`'
- - 3b -
:: ~
: ~ -
.. ...
1~71~2~4
to prevent chronic damage to the skin without inhibiting
the desirable responses to insolation.
; The select conjugated dienes suitable for use in
the compositions of this invention are those capable of
quenching the excited-states of biogenic chromophores con-
tained in aromatic amino and nucleic acids. Although not
, wishing to be bound by theory, it is believed that undesirable
`~ ~ell change resulting ~rom exposuxe to sunlight can be --
. . - .
controlled by inhibiting one or more of the usual photo-
chemical reactions that affect DNA and RNA syntheses.
One of the known ,photochemical reactions that in~luences ,~ `
DNA and RNA syntheses is the photodimerization of
; pyrimidine bases, thymine and cytosine in the case of DNA,
i,,,,, and uracil and cytosine in the case of RNA. Photodimeriza-
tion reactions can be broadly described as the photocyclo-
addition of a ground-state molecule with an excited-state
,, .
` molecule. Certain conjugated diene~ are known excited- ~ ~
.~,
st~te quenchers, see, for example, Lamola, Pure AP~1. Chem.
3~, No. 2, (1973), "Photochemistry and Structure in
Nucleic Acids". Thus, it has been fowld that by utilizing
, conjugated dienes to quench the excited-state of the
, biogenic chromophores, it is possible to inhibit photo-
~, dimerization of the bases and consequently control
. . . undesirable cellular change, i.e., chronic damage.
The class o~ conjugated dienes capable
of quenching the excited-state of biologic chromophores
can be generically described by the following formulae:
' ,
'`
_ a, _
''i .'.'
11~7~;~4~
` R ~ C = C ~ C = C - R
.
wherein each R is -(CH2)nR2 wherein R2 is hydrogen, hydroxyl~
amine, amide, carboxyl, carboxamide, methoxyl, etherically
linked sugar, sulfur heteroatom, or -C(O)OR3 wherein R3 is
S hydrogen, lower a~kyl, methoxyl, hydroxyl, amine, amide,
carboxyl, or phenyl and wherein n is an integer from 1 to
about 10; and wherein the ends of the diene chain may com-
; bine to form a cyclic diene of the formula
:, ' .
~,,; , ~1 11
. R - C = C - C = C - R
J
: ,
',: '. .
i; 10 wherein m is an integer from 1 to about 10; and wherein
~ : each Rl is hydrogen, lower alkyl, or -~CH2)nR2 wherein
,1 R2 is as defined above and n is as defined above.
, , .
` 1 , ,
.
, ' .
.
', ', .
.:~
: )
5 _
, .
:,
7~
The conjugated dienes suitabie fox use herein are
staple items of commerce available from a variety of
chemical manufacturers. In general, conjuyated dienes
can be,synthesized by the acid-catalyzed dehydratiQn of
diols. A detailed description of the synthesis ~f con-
jugated dienes can be found at Chapter 34 of The Chemistry
of Orqanic ComPounds, Noller (ed.), W. B. Saundexs Company,
lg66.
- Conjugated dienes suitable for use in ~ .
1~ this invention include, for example,
:~ (A~ Sulfo~ides such as:
4-(1-cyclohexenyl)-3-butenyl methyl sulfoxide,
3,5-hexadienyl octyl sulfoxide,
3,5-hexadienyl phenyl sulfoxide,
3-ethylidene-4-hexenyl octyl sulfoxide, and
3-ethylidene-4-hexenyl phenyl sulfoxide;
(B) Sulfones such as:
4-(1-cyclohexenyl)-3-butenyl lower alkyl sulfones,
3,5-hexadienyl lower alkyl sulfones,
3,5-hexadienyl phenyl sulfone,
3-ethylidene-4-hexenyl lowex alkyl sulfones, and
3-ethylidene-4-hexenyl phenyl sulfone;
(C) Sulfinyls such as:
1,8-bis (methyl sulfinyl)-3,5-octadiene,
l-(2-lower alkyl sulfinyl-1-ethyl)-1,3-cyclo C6 ~o C8
conjugated dienes,
2-(2-lower alkyl sulfinyl-l-ethyl) 1,3-cyclo C6 to C~
:` conjugated dienes,
.,
~- 6-(2-methyl sulfinyl-1-ethyl)-1,3-cyclo hexadiene,
6-~2-methyl sulfinyl-1-ethyl)-1,3-cyclo heptadiene,
'' .
~ - 6
` ~07~Z~4
2-(2-lower alXyl sulfinyl-l-ethyl)-3-(2-hydroxy-1-ethyl~-
1,3-cyclo C6 tQ C10 conjugated dienes, and , :~
7-tmethyl sulfinyl methyl) cholesta-3,5-diene; :
(D) 5ulfonyls such as: :.
. 5 1,8-bis(lower alkyl sulfonyl~-3,5-octadiene,
2-t2-lower alkyl sulfonyl-1-ethyl)-1,3-cyclo C6 to C8
conjugated d.ienes,
., .
6-(2-lower alkyl sulfonyl~l-ethyl)-1,3-cyclo C6 to C8
: conjugated dienes, and
2-(2-lower alkyl sulfonyl-1-ethyl)-3-(2-hydroxy-1-ethyl)-
... 1,3-cyclo C6 ~o C10 conjugated di~fnes;
. (E) Amfines such as:
2,4-hexadien-1-amine,
1,6-diamino-2,4-hexadiene,
. 15 2-lower alkyl amino-1,3-butadienes,
., l-amino 3,5-heptadiene,
'~ . l-amino-3,5-hexadiene, -
~:; 1,8-diamino-3,5-octadiene,
3-methylene 4-hexene-1-amine,
2Q 3~ amino-2-ethyl)-2,4-hexadiene~
~`~ l-amino-4,6-dodecadiene,
. ~ I-di lower alkyl amino-3,5-hexadienes,
: l,9-bis~di-lower alkyl amino)-4,6-nonadiene,
. l-di-methyl amino-3-methylene-4-hexene,
l-N-phenyl-N-lower alkyl amino-3,5-hexadienes,
l-N-piperidino-3,5-hexadiene,
I l-lower alkyl amino-3,5-heptadienes,
: l 1,2-dihydropyridine,
3-vinyl-1,2,5,6-tetrahydropyridine,
2,7-dihydroazepine,
' !
. ' . . : :
. 2,3,8,9-tetrahydroazonine,
~''','.' . '
~,
. - 7 -
~, :
;. .
.: ~ ...._.
~07V24~
4.~ hydroxy-3-butenyl)-1,2,5,6-tetrahydropyridine,
- 2,3,8,9-tetrahydro-N-lower alkyl azonineS,
1-(2-amino-1-ethyl)-1,3-cyclononadiene,
2-(2-amino-1-ethyl)-1,3-cyclononadiene,
1-(2-di-lower alkyl amino-1-ethyl)-1,3-cyclononadienes,
1J4 bis(2-di-methyl amino-1-ethyl~-1,3-cyclononadiene,
l-t2-piperidino-l-ethyl)-1,3-cyclononadiene; .:
~F) Hydrocarbons such as~
2,3,4,5-tetra~ethyl-2,4-hexadiene,
1,3-decadiene, . ;~;
2,2,7,7-tetramethyl-3,5-octadiene, . ,~
5,6-dimethylene decane,
1,3-eicosadiene,
1,3-cy~lohexadiene,
1,3-cycloheptadiene,
1,3-cyclooctadiene,
1,3-cyclononadiene,
.
1,3-cyclohexadecadiene, :~
butyl-1,3-cyclodecadiene,
, ~20 ~ 2-butyl-1,3-cyclodecadiene,
8-octa-2,4-dienyl)-1,3-cyclononadiene,
l-vinylcyclohexene,
,.j
l-vinylcycloheptene,
l,l'-bis cyclohexene, and
hexalin;
(G) Alcohols such as:
. 2,4-hexadien-1-ol,
: 3,5~heptadi~ ol,
3,5-octadien-1,8-diol,
.; :
:, .
.', ; .
~7(~2
'
3-methylene-4-penten-1-ol,
3-ethylene-4-hexene-1-ol,
6,7-bis~l-hydroxy-2-ethyl)-5,7-dodecadiene,
3-(1-hydroxy-2-ethyl)-1,8-dihydroxy-3,5-octadiene,
9,11-dodecadien-1-ol,
octa-5,7-dien-1,2-diol,
~,6-heptadien-2-ol,
2,9-dihydroxy-2-methyl-4,6-nonadiene,
2,9-dihydroxy-4,6-decadiene,
5-hydroxymethyl-1,~-cyclohexadiene,
2-(1-hydroxy-2-ethyl)-1,3-cyclohexadiene,
2,3-bis(l-hydroxy-2-ethyl)-1,3-cyclohexadiene,
2-(1-hydroxy-2-ethyl)-1,4-dimethyl-3-butyl-1,3-cyclohexad.iene,
l-hydroxy-2-ethyl)-1,3-cycloheptadiene,
2-(1-hydroxy-2-ethyl)-1,3-cycloheptadiene,
2,6-bis(l-hydroxy-2-ethyl)-1,3-cycloheptadiene,
6-(1-hydroxy-2-ethyl)-1,3-cycloheptadiene,
l-(l-hydroxy-2-ethyl)-cyclonona-1,3-diene~ ;
7-hydroxy-1,3-cyclononadiene,
: 20 7-(1-hydroxy-2-ethyl)-1,3-cyclononadiene,
l-hydroxy-2-ethyl)-1,3-cyclotetradecad.ie~e,
2-(l-hydroxy-2-ethyl)-~l(2)~8-he
~1(2),8 6 h 1 1 d
l,l'-bis cyclohexene-4-ol;
(H) Ethers such as:
: , !
. 7-ethoxy-1,3-heptadiene,
l-ethoxy-2,4-hexadiene,
1,6-diethoxy-2,4-hexadiene,
4-(2-ethoxy-1-ethyl)-3,5-heptadien-1-ol,
: ~ '
~ . .
. --
_ g _
~L07~Z44
.
6-glucosyl-1-hepta-2,4-dienyl ether,
l-glucosyl-l-hepta-2,4-dienyl ether, and - .
4,5-dioxo,~l'8-hexalin;
(I) Carboxyls such as:
3,5-hexadienoic acid,
3,5-octadien-1,8-dioic acid,
5,7-nonadienoic acid,
4,6-decadiene-1,10-dioic acid,
s 5-ethylidene-6-octenoic acid,
4-(2-propenyl~-nona-1,9-dioic a~ld,
~ 2-carboxy-5,7-nonadienoic acid,
,; 2-methyl-5,7-nonadienoic acid,
s ~ 2-amino-5,7-nonadienoic acid,
, :
10,12-tridecadienoic acid,
9-hydroxy-4,6-nonadienoic acid,
~.:
l-carboxymethyl-1,3-cyclohexadiene,
2,4-cyclohexadienoic acid,
2-carboxymethyl-1,3-cyclohexadiene,
l-(l-carboxy-2 ethyl)-1,3-cyclohexadiener
2-(1-carboxy-2-ethyl)-6-carboxy-1,3-cyclohexadiene,
1,4-dimethyl-2-(1-carboxy~2-ethyl)-1,3-cyclohexadiene,
2-(1-carboxy-3-propyl)-3-(1-hydroxy-2-ethyl)-1,3-cyclohexadiene,
l-tl-carboxy-2-ethyl)-1,3-cycloheptadiene,
6-(1-carboxy-2-ethyl) 1,3-cycloheptadiene,
:- 25 3,5-cycloheptadienoic acid,
; 2,4-cyclodecadienoic acid,
; 4,6-cyclononadienoic acid,
l ~ l-(l-carboxy-2-ethyl)-1,3-cyclotetradecadiene,
,
~ .
.~ ' - 10 - ': :~
._._ . , .
. ~ .
::~(37~4
(2)'8-hexalin 6-carboxylic acid, and
7(1-carboxy-2-ethyl)-~ ~2)'8-hexalin;
(J) Amides, phenyl amides, and N-lswer aLkyl .
: amidès of the above ~arboxylic acids: .
(K) Lower alky~ esters of the above carboxylic
acids; and
L~ Polyol esters of the above carboxylic acids
:. , .
prepared by the reaction of the above acids and polyols
such as sugars and lower alkanols. Sugars suitable
; 10 for use in the formation of the slagar esters of the
invention include monosaccharides and dlaaccharides.
Examples of suitable monosaccharides include
those carbohydrates which do not hydrolyze such
. as ~lucose, mannose, galactose, arabinose, xylose, ribose,
apitose, rhamnose, fucose, psicose, fructose, sorbose,
;- tagitose, ribulose, zylose, and erythrulose~ Examples of
~ suitable disaccharides include those carbohydrates which
yield only a few molecules of monosaccharides on hydrolysi$
. such as maltose, kojibiose, nigerose, cellobiose, lactose,
- `20 mellbose, gentiob~ose, turanose, rutinose, tremalose,
sucrose, and raffinose. It should be noted that suitable
sugars are characterized by a plurality of hydroxyl groups
.~ which may be converted to ether linkages. For present
purposes, the ether linkage can be formed from any of the
available hydroxyl groups located within the sugar structure
without altering the effectiveness of the diene itself.
. Thus, the present invention contemplates the use of con-
-I jugated dienes, as defined above, having an etherlcally
.. . . .
11 - '
:. ..
.~, ' .
,
~7()'~
linked sugar moiety without regard to the location of the
ether linkage relative to the sugar moiety per se.
As used hereinabove, the term "lower alkyl" is
intended to include Cl to C10 alkyl, for example, methyl,
ethyl~ propyL, butyl, octyl, and decyl.
. Preferred conjugated dienes ~uitable for use
herein include~ for example, sulfoxides such as 3,5- ~ :
hexadienyl octyl sulfoxide; 3,5-hexadienyl phenyl
.sulfoxide; and 3-ethylidene-4-hexenyl octyl suloxide; .
sulfinyls such as 1,8-bis(methyl sulfinyl).-3,5-octadiene,
~ 6-~2-methyl sulfinyl-1-ethyl~-1,3~cyclo hexadiene,
6-(2-methyl sulfinyl-1-ethyl)-1,3-cyclo heptadiene, and
7-(methyl sulfinyl methyl) cholesta-3,5-diene; amines
such as l-amino-3,5-heptadiene, 1,8-diamino-3~5-octadiene,
. 15 1-amino-4,6-dodecadiene, di-methyl amino-3-methylene-4-
.
hexene, 1,4-bis(2-di-methy1 amino-1-ethyl)-1,3-cyclonona-
~- diene, and 1-(2-piperidino-1-ethyl)-1,3-cyclononadiene;
~ hydrocarbons such as 1,3-decadiene,.1,3-cyclononadiene, and
~ 1-(8-octa-2,4-dienyl)-1,3-cycLononadiene; alcohols such ~ :
: `20 ~ as 3,5-heptadien-1-ol, 3,5-octadien-1,8-diol, 3-ethylene-
: 4-hexen-1-ol, 3-(1-hydroxy-2-ethyl)-1,8-di~ydroxy-3,5-
octadiene, 2,9-dihydroxy-4,6-decadi.ene, 2,3-bis(l-hydroxy-
. 2-ethyl)-1,3-cycloheptadiene, ~1t2)'8-6-hexalol; ethers such
:~ as 1,6-diethoxy-2,4-hexadiene, 4-(2-ethoxy-1-ethyl)-3,5-
heptadien-l-ol; and carboxyls such as 3,5-octadien-1,8-
: dioic acid, 4-(2-propenyl)-nona-1,9-dioic acid, 2-methyl-
- 5,7-nonadienoic acid, 9-hydroxy-4,6-nonadienoic acid, and
.. . 2-(1-carboxy-3-propyl)-3-(1-hydroxy-2-ethyl)-1,3-cyclo}lexadiene. .
. Especially preferred conjugated dienes suitable for :.
use herein include, for example, 3,5-hexadienyl octyl
' ' ' ;',
. - ~2 - ;.
:
1~7~Z~L~
sulfoxide; 3,5-hexadienyl phenyl sul~oxide, 3-ethylidene-4-
hexenyl octyl sulfoxide; 1,8-bi~ thyl sulfinyl)-3,5-oct~-
diene; 7-(methyl sulfinyl methyl) cholesta-3,5-diene; l-amino-
3,5-heptadiene; 1,8-diamino-3,5-octadiene; 1-amino-4,6-
dodecadiene; 1-(2-piperidino-1-ethyl)-1,3-cyclononadiene;
1,3-decadiene; 2,4 hexadien-l-ol; 1,3-octadien-5-ol; and
1-(8-octa-~,4-dienyl)-1,3-cyclononadiene.
: It has been found that suitable conjugated dienes can
be structurally tailored to provide not only protection from
chronic damage but also protection from more immediate erythemo-
genic responses by incorporating a sunscreening or ultraviolet
radiation absorbing moiety into the basic diene structure.
Thus, t~e present invention encompasses compositions for topical
protectLon from both erythema and chronic damage.
Especially preferred conjugated dienes structurally
tailored to provide, as`an additional benefit, protection from
erythemogenic responses include, for example, esters and amides
prepared by reaction of conjugated dieneols and amines, such as
those enumexated above, with the acid of an ultraviolet radia-
.
tion screening or absorbing compoundO Specific acids suitable
for use in preparing tailored conjugated dienes include, for
example, p-methoxy cinnamic acid, p~aminobenzoic acid, salicylic
acid, p-dimethyl amino benzoic acid, and uraconic acid.
The composltions of the present invention comprise from
about 0.001% to about 25%, preferably 0.01% to 15%, by weight,
of a con~ugated diene. It has been found that below about
0.001%, by weight, the conjugated dienes do not provide
significant protection from the chronic damage o~ prolonged
exposure to ultraviolet radiation; and that concentrations
above about 25%~ by weight, do not significantly enhance th~
efficacity of the compositions of this invention.
As noted, the present invention encompasses composi-
tions for topically controlling chronlc skin damage
''
~,
- 13
~[)70Z~
comprising a conjugated diene, a~ described above, and
a surfactant-containing vehicle. It has been found that
the surface active agent provides a more ef~icient absorp-
tion and retention by the skin of the active ingredient of
the compositions of this invention. Various vehicles have
been employed to carry the active, and the make-up of the
vehicle profoundly affects the efficacy o~ the product.
Suitable vehicles, once spread on the skin, should remain
in place as a continuous film, closely adhering to or
penetrating the skin surface, and should resist washing
off either by perspiration or by immersion in fresh or
salt water. The characteristics cf a suitable vehicle
vary greatly aepending es~entially upon the ideas and
.
prejudices of the formulator. Creams, cream lotions, oils,
15 gels, hydroalcoholic lotions, jellies, lipsticks and aerosol
foams and sprays are common formulations. In any event,
suitable vehicles contain from about 0.1% to about 10%
of a nonionic, cationic, or amphoteric sur~ace active
agent; the preferred amount is in the range of about 0.1%
to about 2%. The upper limit of such surface active agent
(surfactant) is critical where large amounts may result in
excessive foaming. Cationic, and particularly nonionic,
surface active agents are desirable although anionic non-
soap surfactants are also suitable. Anionic non-soap sur-
factants are preferably used at concentrations of about
0.01% to about 0.5% and desirably below about 0.1%.
l Water-soluble nonionic surfactants are highly suitable
- for use in this invention; they include detergent co~pounds
,
produced by the condensation of alkylene oxide groups
~l 30 (hydrophilic in nature) with an organic hydrophobic
-i compound which may be aliphatic or alkyl aromatic in
,~
.~ .
~`.:~ .~.A___ . __ _ . _ _ _.. _ _, .. _ ... . . . _ . _ .. _.. _ .. __ .. _ _.. _. _.. .. . .. .. _ _.~ .. _ _ . _
.:
F~
!
70Z~
.. . . .
~ature. Examples of such detergents are: the polyalkylene
~' ~ glycol esters, ethers, and thioeth~rs of the types,
,. . .
Rcoo(-c2H4o)n-H~
'~ - RO(-C2~4O) -H, and
, -
wherein R represents long chain alkyl radicals having
from about 8 to about 18 carbon atoms and n is an integer
f ~ from about 4 to about 30; the polyethylene oxide condensates
~f alkyl phenols, e.g., the condensation products of alkyl
~; 10 phenols having about 6 to 12 carbon atoms in the alkyl
group, in either straight chain or branched chain configura-
tion, with ethylene oxide in amounts equal to 10 to 25
~;~ moles of ethylene oxide per mole of alkyl phenol; compounds
~' ~' ' '' ' .
formed by condensing ethylene oxide with a hydrophobic base
formed by the condensation of propylene oxide with propylene
P glycol; th~ condensation product of ethylene oxide with the
product resulting~from the reactlon of propylene oxide and
` ethylene diamine. More specific examples of some suitable
nonionic detergents are: the reaction products o~ t-octyl-
20 phenol with an average of from 9 to 30 moles of ethylene
oxide per mole, and the water-soluble waxy reaction products
,....................... . .. . .
of lauryl alcohol and ethylene oxide having a titer of about
35C or higher and of oleyl alcohol and ethylene oxide
~, , .
having a titer of about 29C or higher.
~r ~' 25 Other examples of nonionic surfactants are: tertiary
, ~ trialkyl amine o~ides wherein one alkyl group contains 10-18
carbon atoms and the other alk~l ~roups are short chain groups
:: .
".'`' - 15 ~
~ 7~
(a specific example is dodecyl dimethyl amine oxide);
hexadecyl dimethyl ammonio propionate; 3-(hexadecyl
dimethyl ammonio)-propane-l-sulfonate.
The preferred nonionic surfactant is available on
the market under the trademark of "Pluronic". These compounds
are formed by condensing ethylene oxide with a hydrophobic
base formed by the condensation of propylene oxide with
~ropylene glycol. The hydrophobic portion of the molecule
exhibits water insolubility. Its molecular weight is of
the order of lS00 to 1800. The addition of polyoxyethylene
radicals to this hydrophobic portion tends to increase the
water solubility of the molecule as a whole. Liquid products
are obtained up to the point where the polyethylene content
is about 50% of the total weight of the condensation product.
Further increase in the relative content of polyoxyethylene
to hydrophobic portion renders the final product wax-like ~ -
or solid in consistency. The molecular weights of Pluronic
L-61, L-64 and F-68 which find particular utility in the
practice of the present invention are about 2000, 3000 and
8000 respectively.
Examples of cationic surfactants suitable for practice ~i
of this invention are the detergent quaternary ammonium salts.
Such salts have the general formula~
' ~ '
"
,, : '' / .
,,
. ~
: . .
.~ .,
- 16 _
~,, . ~,
.. . . . . . .. .
3L , "
, R2 ~ '
1. X . . ~ ;
:
wherein Rl is a hydrophobic radical and R~, R3, and R4 are
~, S each hydrocarbon radicals. Rl can be aliphatic, unsaturated
aliphatic, cycloaliphatic, acyl, aliphaticaryl and aryl-
~.: .. .
~, aliphatic radieals containing 8 to 25 carbon atoms, fe.g.,
branched or normal chain alkyl p~lenoxy alkoxy alkyl,
branched or lfsng chain alkyl cresoxy alkoxy alkylO iong
chain alkoxyaryl, branched or long chain alkyl phenoxy alkyl,long chain alkyl aryl, halogen-substituted long chain alkyl~
,, j~ ~ :
aryl, aryl alkyl, long chain alkyl, long chain alkenyl and~
cycloalkyl. R2, R3, and R~ can contain each 1 to 10 carbon
atoms, with tha total carbon atoms in the three radicals
: .
~- 15 being from 3 to 12. Examples of R2, R3~ and R4 are low
molecular weight alkyl, preferably methyl or ethyl, or
aryl, preferably phenyl, or arylalkyl, preferably benzyl.
'' ~ X i5 a salt forming radlcal which is an anionic
xadical capable of forming a water-soluble salt. Chloride
and bromide are preferred but halides generally, sulfates,
phosphates, methosulfate, and~other salt forming ions are
~ also satisfactory. - ~ r :
., ~ , ' ' ~,'
'`, ' ' ' .
.
'. . ~ , .
'''' ' . : ,
. .
~ 17 - - ~
~ , : .
~C~7~Z44
~ xamples of amphoteric detergellt surfactants are
alkyl beta imino dipropionates and alkyl beta amino propion-
ates, wherein the alkyl group contains 10 to 20 carbon atoms,
and imidazoline derivativ~s of the Miranol~ class. Other
examples of amphoteric surfactants may be found in "Surface
Active Agents and Detergents, Vol. II", Schwartz, Perry and
Berch, pp. 138-143.
Examples of anionic non-soap surfactants suitable for
the practice of this invention are the detergents of the sul-
fonated and sulfated types such as the alkyl (C8-C18) sulfates,
the alkyl (C8-C18) polyethenoxy (1-10 units of -C2H4O-) ether
sulfates, the alkyl (C8-C18) aromatic sulfonates, the mono-
or di-alkyl (C8-C18) esters of sulfosuccinic acid, sulfonated
or sulfated amides of higher fatty acids, sulfuric acid esters
of polyhydric alcohols incompletely esterified with higher
~ fatty acids, higher fatty acids esters of low molecular weight
- ~ alkylol sulfonic acids, etc., usually in the form of their
sodium, potassium, ammonium, or alkanolammonium salts. Some
of the particular detergents of this category are: sodium
octyl sulfate, sodium nonyl sulfate, sodium decyl sulfate,
monoethanolammonium dodecyl sulfate, ammonium tetradecyl sulfate, -
~monoethanol-ammonium pentadecyl sulfate, monoethanolammonium
hexadecyl sulfate, monoethanolammonium octadecyl sulfate,
monoethanol-ammonium oleyl sulfate, sodium salts of dioctyl
sulfosuccinate, sodium octyl benzene sulfonate, sodium nonyl ;
benzene sulfonate, sodium dodecyl benzene sulfonate, sodium
tetradecyl benzene sulfonate, ammonium pentadecyl benzene
sulfonate, ammonium
;~' ' ,
~ 30
-:
- 18 -
:' :
..
~L~70Z~4
triisopropyl benzene sulfonate, sodium salts of the oleic
acid ester of isethionic acid, sodium salt of the lauric
acid amide of taurine, triethanolammonium coconut oil
monoglyceride monosulfate, monoethanolammonium tallow di-
glyceride monosulfate. N lauroyl sarcosinates are alsosuitable.
In addition to a surfactant, the vehicle used herein
may contain solid or liquid diluents, penetrants, thickeners,
stabilizers, preservatives, and the like or mixtures thereof.
Diluents which are suitable for use herein include,
for example, water, ethanol, glycerin, and saline. Particularly
useful diluents are hydrophilic, water-soluble or miscible
diluents, which term, for the sake of convenience, is intended
to include water itself. Hydrophilic diluents generally
lower the freezing point of the diene component so that the
- compositions are useful at temperatures encountered during
cold weather use and storage.
Penetrants which are suitable fox use herein include,
for example, the dialkyl sulfoxides, and the polyoxyethylene
sorbitan higher atty acid monoesters. U.S. Patent 3,740,420
granted July 1~, 1973, describes in detail pharmaceutical
penetration and the use of dialkyl sulfoxides as penetrants.
For various applications, the compositions
herein may be formulated into convenient form for appli-
cation with thic~ening agents. Such forms include thickened
solutions or lotions, ointments, creams, gels, and the like.
These forms are advantageously employed to lessen the run-off
, from the skin that may occur ~ith the most fluid composition
~ '' ' , .
. ~ - 19 - ..
.
.
., ~ .. .
lQ~OZ~4
orms, thereby permitting greater mobility for the user
immediately following application. Accidental spilling
and undesired contact with the material can also be
minimized with these formulations.
It is advantageous to use water dispersihle thickening
agents (i.e., agents dispersible in water to form a homo-
geneous distribution or solution), such as the polyethylene
glycols, as they are readily compatible with water or other
diluents and may be readily washed from the skin. Alter-
10 natively, an emulsion base may be employed to Lmpart the ~ ;~
desired thickening effect, a better spreading and wetting
effect, and a retardation of the skin-drying effect of
certain penetrants.
The water-soluble thickening bases utilize, for
example, a variety of polyethylene glycols having differing
viscosities, depending upon the desired consistency; water-
:, .
dispersible gums; carboxy vinyl polymers, methyl cellulose,
alginates, and the like. The compositions incorporating ~
;~emulsion bases may contain the usual adjuvants such as a ;
`20 fatty alcohol, an emulsifier, and water. ~`
The required application of conjugated diene will
vary with the particular circumstances of application, the
; duration of anticipated exposure, and effectiveness of the
. ,:
carrier component; however, single a~plications
generally range from about 0.25 to about 2 milligrams persquare centimeter of epidermal area with up to 4 applica-
tions daily. Single applica~ions containing greater than
about 2 milligrams per square centimeter are not
:,
. ~. .
'''' ' .
- 20 -
-,, .
7~Z~4
economical in view of the limited enhanced activity resulting
from the additional active present, whereas single applications
containing less than about 0.25 milligrams per square centi-
meter do not have the desired effect.
The skin compatible vehicles employed herein are used
at a concentration sufficient to provide a practical topical
` application. Preferably, the vehicle comprises from about 90%
to about 99.99% by weight of a total composition. Suitable
vehicle formulations are more thoroughly detailed in Cosmetic
Science and Technology , Sagarin (Editor), Interscience Pub-
lishers, New York (1957).
In a preferred embodiment of the invention a suitable
conjugated diene and surfactant containing carrier are com~
bined with 1~ to 10%, by weight, of a sunscreening or ultra-
violet radiation absorbing agent to provide compositions which
not only inhibit the chronic damage attributed to prolonged
exposure to sunlight but also provide immediate protection from
erythema. A wide variety of screening and absorbing agents
are suitable for use in combination with the conjugated dienes
of this invention. Sagarin, et al. at Chapter VIII, pages
189 et seq., of Cosmetics Science and Technology disclose
numerous suitable agents. Specific suitable sunburn preventing
agents include, for example,
: '
': ' ;, ':
' -
"
' -' - ' ~ :
` ;
-' . ~. '
- 21 -
j.,
.- ,t~. ;,
,.,
: , , . ,:
- - :
@'Dt
7(~Z~4
E~-Aminobenzoic acid, its salts and its derivatives
~ethyl, i50butyl, glyceryl esters; E~-dlmethylaminobenzoic
acid~;
Anthranilates (i.e., o-aminobenzoates; methyl,
menthyl, phenyl, benzyl, phenylethyl, lina~yl, terpinyl,
-; and cyclohexenyl esters); . - :~
Salicylates (amyl, phenyl, benzyl, menthyl, glyceryl, ,:
and dipropyleneglycol esters);
~: . Cinnamic acid derivatives tmenthyl and benzyl esters,
~-phenyl cinnamonitrile, butyl ~innamoyl pyruvate);
~ihydroxycinnamic acid derivatives (umbelliferone, .:
~ethylumbelliferone, methylaceto-umbelliferone);
Trihydroxycinnamic acid derivatives (esculetin, : ~:
methylesculetin, daphnetin, and the glucosides, esculin
and daphnin); . :
-: :
.:! Hydrocarbons (diphenylbutadiene, stilbene); : :
. Dibenzalacetone and benzalacetophenone;
Naphtholsulfonates (sodium salts of 2-naphthol.-3,6-
- disulfonic and of 2-naphthol-5,8-disulfonic acids); ~:
~20 Dihydroxy-naphthoic acid and its salts; :
. o- and ~-Hydroxybiphenyldisulfonates;
; . Coumarin derivatives (7-hydroxy, 7-methyl, 3-phenyl);
Diazoles (2-acetyl-3-bromo.~ndazole, phenyl benzoxazole,
. methyl naphthoxazole, various aryl benzothiazoles);
. j .
Quinine salts (bisulfate, sulfate, chloride, oleate,
and tannate);
. ; .
',!, Quinoline derivatives (8-hydroxyquinoline salts,
.; 2-phenylquinoline);
. .
:~ .
Hydroxy or methoxy-substituted benzophenones;
,,
. .
-- 22 _
.~
7~ 4
Uric and vilourLc acids;
. Tannic acid and its derivatives ~e.g., hexaethylether);
. (Butyl carbityl) (6-propyl piperonyl) ether; and
Hydroquinone.
~: S The following examples are intended to illustrate
suitable compositions and methods of their use.
, ~ .
~ . .
.' ~ .
,, ~ . . .
.` ,,. ,.
3 ' .
,
. ' :-
~, :
, . . . .
.
1:'` ` ~ I : ~
.~, . : ~
~:'', ' ~', ~.'
,, :-
.:,"i, ':
:~ i
... ...
.. . . . .
: ' .
_ 23 -
-'~; '
.. .. : . :.. . . .. . .
~7~)Z4~
EXAMPI,E I
The following solutions were prepared by mechanically
blending the recited ingredients in the indicated proportions
at room temperature.
Ingredients ~ by Weight of Total
Composition
.. . .
A B C
2,4-hexadienol 54
5-hydroxy-1,3-octadiene 5%
Ethanol 72~ 72% 75
- 10
~ Water 23~ 23% 25%
- The cl~ipped backs (approximate area 36 square centi-
meters) of three groups of twenty Fischer female rats were
topically treated with 0.5 milliliter aliquots of Composition
A, B or C~ Approximately 3 to 4 hours after application,
the animals were exposed to ultraviolet radiation emitted by
a bank of four Westinghouse Fluorescent Sunlamps, Model
FS-40 ~ for a one-hour period. The period of exposure was
calculated as equivalent to three times the minimum erythemal ~
'`
dose. The treatment and exposure were repeated three times
a week for twenty-five weeks. The animals were graded every
week based upon the degree of visible irritation using a standard
scale ranging from 1 to 3.
, . .
`: ~, ' :
3~
,. :
.,. . c~ ~ .
` ` 107~)~4~
.
Repeated exposurè to ultraviolet radiation is
. known to result in irritation varying from erythema to
- scaling, ulceration, and severe necrosis. The animals
treated ~ith Composition C during the exposure period
: 5 underwent marked changes ultimately reaching an average
: severity grade of 7Ø In contrast, those animals
receiving treatment by either Composition A or B showed
only mild to moderate irritation, ultimately reaching
an average sevexity grade of 3.0 in the case of Composition
A and 4.8 in the case of Composition B.
, ' - . .
., ' .
,, .,
., , , . : " '.
. ~, .
.. . ' : .'' !
" . . ...
. . : ' . ' ' . .
i, ",,
.'~`' . ' ~.',
,. ~ '' ,
~: ' . . '~
~ ' ',: ' '~,' '
,~, , , ,
~ ~ ' .'
'.. ,'' . ~ '
"': j ' ' ' ~ :
:: '
: 25 ~ .
,:
37C~Z~
. . . . .
EXAMPLE II
The followiIlg cream base composition is pxepared
' by conventional methods. .
~' : , ' ' . , .
Ingredients . % by weight of ~:~
Total Composition :
3,5-hexadienyl octyl sulfoxide 10%
.Stearic acid 15%
Propylene glycol 25% :
Mineral oil . . 5%
Steary1 a lcohol- 1%
Polyoxyethylene sorbitan mono-
. stearate 2%
., Ascorbic acid ' 0.5%
~;' Sodium bisulfite 0.25%
15 Water
I Balance
"
When applied topically, the above composition
provides substantially complete protection from the
, . chronic ef~ects of prolonged expo~ure to ultraviolet
radiation.
~, 20 AdditionaI emollient, cream and lotion compositions
j are prepared in accordance with the present invention as :
ollows:
'' : - , ~
: i.l ~ ~,
:~', ' '
:,,
.. , , . '
. - ~6
` 1~7(;~
X '~
~: . ' -I ,. . .
t)
-
~
.~ ~ H ~ U~
.,
Ei ~1 , . ..
.- c~ ~ æ ~,,, ~ '~. :
. ~ ~ . ~; .
: '
I ~ g,,, I ~,, ,, æ
.
Ul ~ ~, ~ ~ ~ ~ ,,~
H I I I I I I I I tr) " I u~ 0
. ' ''' .
" ~ t ' I I
. ' ' ' , - ,~
H I I I I I I I I ~1 I ' --I --I I
,: , O ~ .'.
:'.i : , ~ ', :
~a ~
;- ' o ~ la !
0 ~ U /D .-~ ' '
' i rl I O ' I
~'' X ~ U~
"~ O ~ ~ U .
~'; U I ~I
O ~
X --I ~I ~ U ~ I O
~ ~ ~ C ~ I q) 1 0
"/ .~ X ~ ~ ~ O ~ O ~1 0 U X o ~ ~ ~ U ~
~J ~5 S ,q ~J 11') rl ~ :~rl I U ~ ~ I X ~ ; h O h
: I ~ I E~ h O ~ a ~ O ,S: r~5 ~ h
U Ul ~J 0 --~ Il) j tO --' U ~ 0 O ~ h ~ ~ ~ O ~ ~ -
~ ~ ~ a m ~
-
~ . - -: ~ O ~ o , U- ,
~ .
~ 27 ~
r
~7~4 - ~
. . ` . ., - ~ '
' ' -
When topically applied the compositions of the
oregoing Examples provide substantially complete
protection from the chronlc effec~s of prolonged exposure
. : to ultraviolet radiation~
. , .
,
, ' :- , ', ' ':
;- ~ . . ~ .
~ XAMPLE XII .- ` `
,
~` The following.solution base composition is . ~ .
:~ prepared in accordance with the invention as follows~
! ` ~ ` ~
. P-methoxy cinnamic acid ester 12%
I of 2,4-hexadien-l-ol
:~l lO Cetyl alcohol ~% ~. :
.~ 1anolin l%
~ Mineral oil 2%
-~ Polyethylene glycol monostearate 1~
~.................................................... .
: Pectin 1~
.`~ 15 ~later
Balance
,, , ~ . ,
. : ,
,.~ ,
;:, .
: . , .
In the above composition the p-methoxy cinnamic
!~ acid ester of 2,4-hexadienol is replaced by the esters
.. . . .
o* p-amino benzoic acid, salicylic acid, and p-dimethyl
amino benzoic acid and 3,5-heptadlen-l-ol, 3,5-octadien-
20 1,8-diol, 3-ethylen~-~-hexen-l-ol,-3~ hydroxy-2-ethyl)- .
l,8-~ihydroxy-3,5-octadiene, 2,9-dihydroxy-4,G-decadiene, `~
2,3-bis5l-hydro~y-2-ethyl)-l,3-cyclohexadiene, and :
~ ) -6-hexalol
:~,
:~ . ~ 2
.. . . ~ .
- .- ,: . .
la70~44 ' ' . -~
~ en topically applied the above compositions
proYide substantially complete protection from the
chronic effects of prolonged ~xposure to sunlight,
a~; well as protection from sunburn.
Wllat is c:laimed is: . . . . . ;
,
:~ : ,
~, ~
