U.S. patent application number 12/066518 was filed with the patent office on 2010-03-11 for organic compounds.
This patent application is currently assigned to GIVAUDAN SA. Invention is credited to Andreas Natsch, Michael Wasescha.
Application Number | 20100063011 12/066518 |
Document ID | / |
Family ID | 35221322 |
Filed Date | 2010-03-11 |
United States Patent
Application |
20100063011 |
Kind Code |
A1 |
Natsch; Andreas ; et
al. |
March 11, 2010 |
Organic compounds
Abstract
The invention relates to organic compounds having the ability to
reduce or suppress the onset of skin irritation induced by
extraneous cause selected from the group of 2-heptylcyclopentanone,
2-ethoxynaphthalene; 2-methoxynaphthalene;
1-methoxy-4-(prop-1-enyl)benzene;
1-(cyclopropylmethyl)-4-methoxybenzene; ##STR00001## wherein X, Y,
and R.sup.1 to R.sup.11 have the same meaning as given in the
description. Furthermore the invention refers to compositions for
topical application to the skin comprising them. It further relates
to a method of reducing or suppressing the formation of skin
irritation.
Inventors: |
Natsch; Andreas; (Uetikon,
CH) ; Wasescha; Michael; (Bassersdorf, CH) |
Correspondence
Address: |
PARFOMAK, ANDREW N.;NORRIS MCLAUGHLIN & MARCUS PA
875 THIRD AVE, 8TH FLOOR
NEW YORK
NY
10022
US
|
Assignee: |
GIVAUDAN SA
Vernier
CH
|
Family ID: |
35221322 |
Appl. No.: |
12/066518 |
Filed: |
September 8, 2006 |
PCT Filed: |
September 8, 2006 |
PCT NO: |
PCT/CH06/00481 |
371 Date: |
October 17, 2008 |
Current U.S.
Class: |
514/166 ; 512/20;
512/21; 512/6; 514/159; 514/543 |
Current CPC
Class: |
A61K 8/33 20130101; A61K
8/368 20130101; A61Q 13/00 20130101; A61K 8/37 20130101; A61K 31/05
20130101; A61Q 15/00 20130101; A61K 31/275 20130101; A61K 8/35
20130101; A61K 2800/75 20130101; A61K 8/40 20130101; A61Q 19/00
20130101; A61K 8/347 20130101 |
Class at
Publication: |
514/166 ;
514/543; 514/159; 512/6; 512/21; 512/20 |
International
Class: |
A61K 31/235 20060101
A61K031/235; A61Q 19/00 20060101 A61Q019/00; A61K 8/37 20060101
A61K008/37; A61K 8/40 20060101 A61K008/40; A61K 8/33 20060101
A61K008/33; A61Q 13/00 20060101 A61Q013/00 |
Foreign Application Data
Date |
Code |
Application Number |
Sep 12, 2005 |
GB |
0518558.2 |
Claims
1. A topical skin care composition comprising as actives (a) at
least one compound of the formula ##STR00011## wherein R is
hydrogen or isopropyl; R.sup.1 is methyl or ethyl; and R.sup.2 is
C.sub.1-C.sub.6 alkyl or C.sub.2-C.sub.6 alkenyl; or R.sup.1 and
R.sup.2 together with the carbon atom to which they are attached
form a C.sub.5 or C.sub.6 cycloalkyl ring; and the dotted line
together with the carbon carbon bond represents a single bond or a
double bond; (b) at least one compound of the formula ##STR00012##
wherein Y is a C.sub.4-C.sub.7 hydrocarbon residue; and (c) a
cosmetically acceptable carrier; wherein the total amount of
actives is 0.2 to 2 weight % based on the topical skin care
composition.
2. A topical skin care composition according to claim 1 comprising
as actives (a) at least one compound selected from
2-cyclohexylidene-2-phenylacetonitrile,
2-cyclopentylidene-2-phenylacetonitrile and
3-ethyl-2-phenylpent-2-enenitrile; and (b) at least one compound
selected from n-hexyl salicylate, cis-3-hexen-l-yl salicylate,
cyclohexylsalicylate, amylsalicylate, isobutylsalicylate, and
phenethyl salicylate.
3. A topical skin care composition comprising as actives (a) at
least one compound of the formula ##STR00013## wherein R.sup.4 is
methyl or ethyl and I) R.sup.3 is hydrogen and R.sup.5 is
--CH.sub.2--O--R.sup.6, wherein R.sup.6 is methyl or isopropyl; or
II) R.sup.3 is --C(O)--R.sup.7, wherein R.sup.7 is benzyl, and
R.sup.5 is --CH.sub.2--CH.dbd.CH.sub.2 (b) at least one compound of
the formula ##STR00014## wherein R.sup.8 is methyl, C.sub.3-C.sub.4
alkyl, C.sub.3-C.sub.4 alkenyl, --(CH.sub.2).sub.2--Ph, or
--CH.dbd.CH--Ph; X is --CH.dbd.CH--CH.sub.2-- or
--(CH.sub.2).sub.n--, wherein n is 1 or 2; and R.sup.9 is isobutyl
or phenylethyl; (c) a cosmetically acceptable carrier; wherein the
total amount of actives 0.2 to 2 weight % based on the topical skin
care composition.
4. A topical skin care composition according to claim 1 further
comprising as actives at least one compound of the formula
##STR00015## wherein R.sup.4 is methyl or ethyl and I) R.sup.3 is
hydrogen and R.sup.5 is --CH.sub.2--O--R.sup.6, wherein R.sup.6 is
methyl or isopropyl; or II) R.sup.3 is --C(O)--R.sup.7, wherein
R.sup.7 is benzyl, and R.sup.5 is --CH.sub.2--CH.dbd.CH.sub.2.
5. A topical skin care composition according to claim 1 further
comprising as actives at least one compound of the formula
##STR00016## wherein R.sup.8 is methyl, C.sub.3-C.sub.4 alkyl,
C.sub.3-C.sub.4 alkenyl, --(CH.sub.2).sub.2--Ph, or
--CH.dbd.CH--Ph; X is --CH.dbd.CH--CH.sub.2-- or
--(CH.sub.2).sub.n--, wherein n is 1 or 2; and R.sup.9 is isobutyl
or phenylethyl.
6. A topical skin care composition comprising about 0.5 to about 3
weight % of a fragrance composition which comprises as actives at
least 30 weight % based on the fragrance composition of (a) at
least one compound of the formula ##STR00017## wherein R is
hydrogen or isopropyl; R.sup.1 is methyl or ethyl; and R.sup.2 is
C.sub.1-C.sub.6 alkyl or C.sub.2-C.sub.6 alkenyl; or R.sup.1 and
R.sup.2 together with the carbon atom to which they are attached
form a C.sub.5 or C.sub.6 cycloalkyl ring; and the dotted line
together with the carbon-carbon bond represents a single bond or a
double bond; and (b) at least one compound of the formula
##STR00018## wherein Y is a C.sub.4-C.sub.7 hydrocarbon residue;
and the topical skin care composition comprising at least 0.2
weight % of actives based on the skin composition.
7. A topical skin care composition according to claim 1 wherein the
skin composition is a cosmetic product.
8. A fragrance composition comprising at least 30 weight % of at
least two actives selected from the group consisting of (a)
compounds of the formula ##STR00019## wherein R is hydrogen or
isopropyl; R.sup.1 is methyl or ethyl; and R.sup.2 is
C.sub.1-C.sub.6 alkyl or C.sub.2-C.sub.6 alkenyl; or R.sup.1 and
R.sup.2 together with the carbon atom to which they are attached
form a C.sub.5 or C.sub.6 cycloalkyl ring; and the dotted line
together with the carbon carbon bond represents a single bond or a
double bond; (b) compounds of the formula ##STR00020## wherein Y is
a C.sub.4-C.sub.7 hydrocarbon residue; (c) compounds of the formula
##STR00021## wherein R.sup.4 is methyl or ethyl and I) R.sup.3 is
hydrogen and R.sup.5 is --CH.sub.2--O--R.sup.6, wherein R.sup.6 is
methyl or isopropyl; or II) R.sup.3 is --C(O)--R.sup.7, wherein
R.sup.7 is benzyl, and R.sup.5 is --CH.sub.2--CH.dbd.CH.sub.2, (d)
compounds of the formula ##STR00022## wherein R.sup.8 is methyl,
C.sub.3-C.sub.4 alkyl, C.sub.3-C.sub.4 alkenyl,
--(CH.sub.2).sub.2--Ph, or --CH.dbd.CH--Ph; X is
--CH.dbd.CH--CH.sub.2-- or --(CH.sub.2).sub.n--, wherein n is 1 or
2; and R.sup.9 is isobutyl or phenylethyl; (e) compounds of the
formula ##STR00023## wherein R.sup.10 is hydrogen or methyl; and
R.sup.11 is a C.sub.3-C.sub.4 alkyl, e.g. isopropyl, isobutyl or
tert-butyl, and (f) 2-heptylcyclopentanone, 2-ethoxynaphthalene,
2-methoxynaphthalene, 1-methoxy-4-(prop-1-enyl)benzene and
1-(cyclopropylmethyl)-4-methoxybenzene.
9. A fragrance composition according to claim 8 comprising at least
two actives are selected from at least two of groups (a), (b), (c),
(d), (e) and (f) of compounds.
10. A fragrance composition according to claim 8 comprising at
least 30 weight % comprising at least four actives selected from
groups (a), (b), (c), (d), (e) and (f) of compounds.
11. A fragrance composition according to claim 8 comprising at
least 30 weight % of at least four actives characterized in that
four actives or more are selected from different groups (a), (b),
(c), (d), (e) and (f) of compounds.
12. A method for the preparation of topical skin care compositions
comprising the step of including in the skin care composition at
least one compound selected from the group consisting of (a)
compounds of the formula ##STR00024## wherein R is hydrogen or
isopropyl; R.sup.1 is methyl or ethyl; and R.sup.2 is
C.sub.1-C.sub.6 alkyl or C.sub.2-C.sub.6 alkenyl; or R.sup.1 and
R.sup.2 together with the carbon atom to which they are attached
form a C.sub.5 or C.sub.6 cycloalkyl ring; and the dotted line
together with the carbon carbon bond represents a single bond or a
double bond; (b) compounds of the formula ##STR00025## wherein Y is
a C.sub.4-C.sub.7 hydrocarbon residue; (c) compounds of the formula
##STR00026## wherein R.sup.4 is methyl or ethyl and I) R.sup.3 is
hydrogen and R.sup.5 is --CH.sub.2--O--R.sup.6, wherein R.sup.6 is
methyl or isopropyl; or II) R.sup.3 is --C(O)--R.sup.7, wherein
R.sup.7 is benzyl, and R.sup.5 is --CH.sub.2--CH.dbd.CH.sub.2, (d)
compounds of the formula ##STR00027## wherein R.sup.8 is methyl,
C.sub.3-C.sub.4 alkyl, C.sub.3-C.sub.4 alkenyl,
--(CH.sub.2).sub.2--Ph, or --CH.dbd.CH--Ph; X is
--CH.dbd.CH--CH.sub.2-- or --(CH.sub.2).sub.n--, wherein n is 1 or
2; and R.sup.9 is isobutyl or phenylethyl; (e) compounds of the
formula ##STR00028## wherein R.sup.10 is hydrogen or methyl; and
R.sup.11 is a C.sub.3-C.sub.4 alkyl, e.g. isopropyl, isobutyl or
tert-butyl, and (f) 2-heptylcyclopentanone, 2-ethoxynaphthalene,
2-methoxynaphthalene, 1-methoxy-4-(prop-1-enyl)benzene and
1-(cyclopropylmethyl)-4-methoxybenzene.
13. A method of reducing the onset of skin irritation by applying
to the skin an effective amount of a topical skin care composition
comprising at least 30 weight % of a fragrance composition
containing at least two actives as defined in claim 12, with the
proviso that the topical skin care composition comprises at least
0.2 weight % of actives based on the total amount of the skin
composition.
14. A method of reducing the onset of skin irritation comprising:
(A) providing a topical skin care composition comprising at least
30 weight % of a fragrance composition containing at least two
actives as defined in claim 12, with the proviso that the topical
skin care composition comprises at least 0.2 weight % of actives
based on the total amount of the skin composition; and (B)
topically applying to the skin an effective amount of the
composition of step (A) for reducing skin irritation.
15. A topical skin care composition according to claim 4 further
comprising as actives at least one compound of the formula
##STR00029## wherein R.sup.8 is methyl, C.sub.3-C.sub.4 alkyl,
C.sub.3-C.sub.4 alkenyl, --(CH.sub.2).sub.2--Ph, or
--CH.dbd.CH--Ph; X is --CH.dbd.CH--CH.sub.2-- or
--(CH.sub.2).sub.n--, wherein n is 1 or 2; and R.sup.9 is isobutyl
or phenylethyl.
Description
[0001] The present invention relates to organic compounds having
the ability to reduce or suppress the formation of skin irritation
induced by extraneous causes, and to compositions comprising them
for topical application to the skin. It further relates to a method
of reducing or suppressing the onset of skin irritation by
extraneous causes.
[0002] The human skin is constantly exposed to environmental
stresses, such as heat and cold, air pollution, exceptionally dry
air or exaggerated UV irradiation. A further form of stress can
come from the application of cosmetic products or personal wash
products. For example, certain soap acids and some surfactants, in
particular anionic and cationic surfactants, are known to stress
the skin. Antiperspirant salts, such as aluminum salts and
zirconium salts contained in antiperspirant products, retinol and
derivatives thereof contained in anti-aging products,
.alpha.-hydroxy acids such as glycolic acid or lactic acid
contained in anti-wrinkle products are also known to stress the
skin.
[0003] It is known from the art that prostaglandins are mediators
being formed upon a wide variety of different forms of external
stress applied to the human skin, which may become apparent in
redness of the skin, particularly on normal, healthy skin. Thus
there is a need for additives in topical application compositions,
such as cosmetic products and personal wash products, which
suppress or reduce the formation of prostaglandins, in particular
prostaglandin E.sub.2 (PGE.sub.2).
[0004] Surprisingly the inventors have found that certain classes
of chemical compounds, most of which are known as fragrance
ingredients, have the ability to reduce or suppress the formation
of prostaglandins in skin cells.
[0005] Thus the present invention refers in one aspect to the use
of a compound for the preparation of topical skin care compositions
for reduction of skin irritation, wherein the compound is selected
from the list consisting of [0006] (a) compounds of the formula
[0006] ##STR00002## [0007] wherein [0008] R is hydrogen or
isopropyl; [0009] R.sup.1 is methyl or ethyl; and R.sup.2 is
C.sub.1-C.sub.6 alkyl or C.sub.2-C.sub.6 alkenyl; or [0010] R.sup.1
and R.sup.2 together with the carbon atom to which they are
attached form a C.sub.5 or C.sub.6 cycloalkyl ring; and [0011] the
dotted line together with the carbon carbon bond represents a
single bond or a double bond; [0012] (b) compounds of the
formula
[0012] ##STR00003## [0013] wherein Y is a C.sub.4-C.sub.7
hydrocarbon residue, e.g. cyclohexyl, n-hexyl, n-pentyl, iso-butyl,
cis-3-hexen-1-yl, phenethyl, and 1-methyl-hex-3-en-1-yl; [0014] (c)
compounds of the formula
[0014] ##STR00004## [0015] wherein [0016] R.sup.4 is methyl or
ethyl and [0017] I) R.sup.3 is hydrogen and R.sup.5 is
--CH.sub.2--O--R.sup.6, wherein R.sup.6 is methyl or isopropyl; or
[0018] II) R.sup.3 is --C(O)--R.sup.7, wherein R.sup.7 is benzyl,
and R.sup.5 is --CH.sub.2--CH.dbd.CH.sub.2, [0019] (d) compounds of
the formula
[0019] ##STR00005## [0020] wherein [0021] R.sup.8 is methyl,
C.sub.3-C.sub.4 alkyl, C.sub.3-C.sub.4 alkenyl,
--(CH.sub.2).sub.2--Ph, or --CH.dbd.CH--Ph; [0022] X is
--CH.dbd.CH--CH.sub.2-- or --(CH.sub.2).sub.n--, wherein n is 1 or
2; and [0023] R.sup.9 is isobutyl or phenylethyl; [0024] (e)
compounds of the formula
[0024] ##STR00006## [0025] wherein [0026] R.sup.10 is hydrogen or
methyl; and [0027] R.sup.11 is a C.sub.3-C.sub.4 alkyl, e.g.
isopropyl, isobutyl or tert-butyl, and [0028] (f)
2-heptylcyclopentanone, 2-ethoxynaphthalene, 2-methoxynaphthalene,
1-methoxy-4-(prop-1-enyl)benzene and
1-(cyclopropylmethyl)-4-methoxybenzene.
[0029] Particularly preferred is the use of compounds selected from
the list consisting of 2-cyclohexylidene-2-phenylacetonitrile,
2-cyclopentylidene-2-phenylacetonitrile,
3-ethyl-2-phenylpent-2-enenitrile,
2-ethoxy-4-(isopropoxymethyl)phenol,
2-ethoxy-4-(methoxymethyl)phenol, phenethyl cinnamate,
4-allyl-2-methoxyphenyl 2-phenylacetate, n-hexyl salicylate,
cis-3-hexen-1-yl salicylate, cyclohexylsalicylate (=cyclohexyl
2-hydroxybenzoate), amylsalicylate (=pentyl 2-hydroxybenzoate),
isobutylsalicylate (=isobutyl 2-hydroxybenzoate), phenylethyl
benzoate, benzyl 2-methylbut-2-enoate,
2-methyl-3-(4-isopropylphenyl)propanal, isobutyl benzoate, cinnamyl
cinnamate, phenethyl salicylate,
2-methyl-3-(4-(2-methylpropyl)phenyl)propanal,
2-heptylcyclopentanone, 2-ethoxynaphthalene, 2-methoxynaphthalene,
1-methoxy-4-(prop-1-enyl)benzene, phenethyl pivalate,
1-(cyclopropylmethyl)-4-methoxybenzene, cinnamyl acetate,
3-(4-tert-butylphenyl)propanal, phenethyl 2-methylbutanoate, and
phenethyl isobutyrate.
[0030] The availability of a greater number of compounds, which in
addition to their odoriferous properties, have the ability to
reduce or suppress the formation of skin irritation provides the
perfumer with an adequate amount of molecules some of which posses
quite varied odor notes, to create hedonically attractive fragrance
compositions while providing reduction of skin irritation and/or
redness reduction activity to the skin to which it is applied. In
particular, the use of multiple perfume ingredients permits the
design of hedonically attractive fragrance accords.
[0031] The actives for reducing skin irritation as hereinabove
described may be combined with all known odorant molecules selected
from the extensive range of natural products and synthetic
molecules currently available, such as essential oils, alcohols,
aldehydes and ketones, ethers and acetals, esters and lactones,
macrocycles and heterocycles, and/or in admixture with one or more
ingredients or excipients conventionally used in conjunction with
odorants in fragrance compositions, for example, carrier materials,
and other auxiliary agents commonly used in the art. Such
ingredients are, for example, described in "Perfume and Flavor
Materials of Natural Origin", S. Arctander, Ed., Elizabeth, N.J.,
1960; "Perfume and Flavor Chemicals", S. Arctander, Ed., Vol. I
& II, Allured Publishing Corporation, Carol Stream, USA, 1994;
and "International cosmetic ingredient dictionary" 6.sup.th ed.,
The Cosmetic, Toiletry and Fragrance Association, Inc., Washington,
1995.
[0032] While lower concentrations of the active compound show an
effect in a cell culture system, as can be seen from the examples,
higher concentrations in personal care products are necessary to
allow for an effective concentration on the human skin even if, for
example part of the product may be removed by abrasion of clothes
or may be diluted by sweat. Furthermore, the healthy skin acts as a
barrier which limits the penetration of the active compounds.
Generally, the concentration of active compound needed for
efficaciousness on skin is from about 50 to 100 times higher than
that needed in in-vitro tests. The usual perfume concentration in a
topical cosmetic product is about 0.3 to 2% by weight. In general,
the amount of actives applied is in the range of from 0.2 to 2% by
weight, based on the end-product applied to the skin, the amounts
applied usually being in the range of from 0.3 to 1% by weight.
[0033] Thus the present invention refers in a further aspect to
fragrance compositions comprising at least 30 weight % based on the
total fragrance composition of at least two actives for reducing
skin irritation as hereinabove described.
[0034] Whereas some active compounds may be used in relatively high
amounts in a fragrance composition others which are known to be
very powerful odorants, such as Neroline.TM. and Propyl Diantilis,
may be used only in smaller amounts in order to avoid negatively
effecting the overall hedonic impression of the fragrance
composition. In general, as the overall proportion of the active
compound in the fragrance composition rises, so should the number
of active compounds used. For example, a fragrance composition
comprising more than 40 weight % of active compounds should
preferably contain at least 4 different actives, a fragrance
composition comprising more than 50 weight % of active compounds
should preferably contain at least 5 different actives, and a
fragrance compositions comprising more than 60 weight % of active
compounds should preferably contain at least 6 different actives.
Thus, in a further aspect the present invention refers to fragrance
compositions comprising at least 30 weight % of at least three,
four or five actives for reducing skin irritation. Optionally the
fragrance composition according to the present invention comprises
at least two, three or four actives of which are selected from a
different group of compounds, namely group (a), (b), (c), (d), (e),
and (f) as hereinabove described.
[0035] From a hedonic point of view the actives are selected from
two different group of compounds. In particular embodiments are
fragrance compositions comprising a compound of formula (a) and a
compound of formula (b), and fragrance compositions comprising a
compound of formula (c) and a compound of formula (d) or (d'). As
can be seen from the examples, fragrance compositions which are
both hedonically attractive and which have irritation reducing
properties may be prepared, for example, if the composition
comprises at least four active compounds, each of which is selected
from a different group of compounds.
[0036] In an other embodiment the invention is directed to
fragrance compositions comprising [0037] (a) at least one compound
of the formula
[0037] ##STR00007## [0038] wherein [0039] R is hydrogen or
isopropyl; [0040] R.sup.1 is methyl or ethyl; and R.sup.2 is
C.sub.1-C.sub.6 alkyl or C.sub.2-C.sub.6 alkenyl; or [0041] R.sup.1
and R.sup.2 together with the carbon atom to which they are
attached form a C.sub.5 or C.sub.6 cycloalkyl ring; and [0042] the
dotted line together with the carbon carbon bond represents a
single bond or a double bond; [0043] (b) at least one compound of
the formula
[0043] ##STR00008## [0044] wherein Y is a C.sub.4-C.sub.7
hydrocarbon residue, e.g. cyclohexyl, n-hexyl, n-pentyl, iso-butyl,
cis-3-hexen-1-yl, phenethyl, and 1-methyl-hex-3-en-1-yl; [0045] (c)
at least one compound of the formula
[0045] ##STR00009## [0046] wherein [0047] R.sup.4 is methyl or
ethyl and [0048] I) R.sup.3 is hydrogen and R.sup.5 is
--CH.sub.2--O--R.sup.6, wherein R.sup.6 is methyl or isopropyl; or
[0049] II) R.sup.3 is --C(O)--R.sup.7, wherein R.sup.7 is benzyl,
and R.sup.5 is --CH.sub.2--CH.dbd.CH.sub.2; and [0050] (d) at least
one compound of the formula
[0050] ##STR00010## [0051] wherein [0052] R.sup.8 is methyl,
C.sub.3-C.sub.4 alkyl, C.sub.3-C.sub.4 alkenyl,
--(CH.sub.2).sub.2--Ph, or --CH.dbd.CH--Ph; [0053] X is
--CH.dbd.CH--CH.sub.2-- or --(CH.sub.2).sub.n--, wherein n is 1 or
2; and [0054] R.sup.9 is isobutyl or phenylethyl.
[0055] Furthermore, the present invention refers to topical skin
care compositions, such as cosmetic products and personal wash
products, comprising about 0.2 to about 3 weight %, preferably
about 0.5 to about 2.5 weight % of a fragrance composition, the
fragrance composition containing at least 30 weight % of at least
two actives selected from the group (a), (b), (c), (d), (e), and
(f) as hereinabove described, with the proviso that the topical
skin care composition comprises at least 0.2 weight % of actives
based on the total amount of the skin composition. In particular
embodiments are topical skin care compositions wherein the
fragrance composition containing a compound of formula (a) and a
compound of formula (b), and topical skin care composition wherein
the fragrance composition containing a compound of formula (c) and
a compound of formula (d) or (d').
[0056] In another aspect the present invention is directed to a
method of reducing the onset of skin irritation by applying to the
skin an effective amount of a topical skin care composition
comprising a fragrance composition, the fragrance composition
containing at least 30 weight % based on the total fragrance
composition of at least two actives as defined hereinabove, with
the proviso that the topical skin care composition comprises at
least 0.2 weight % of actives based on the total amount of the skin
composition.
[0057] An "effective amount" is generally achieved if about 5-50
mg/cm.sup.2 skin or about 0.05 to about 0.5 mm thick film of the
topical skin product is applied to the skin.
[0058] As used within the meaning of the present invention the
expression "at least 30 weight %" includes fragrance compositions
comprising at least 35, 40 or even 45 or 50 weight % of at least
two actives as defined hereinabove. The term "actives" and "active
compounds" as used within the meaning of the present invention
refers to all compounds selected from the list of compounds of
formula (a), (b), (c), (d), (d'), (e) and 2-heptylcyclopentanone,
2-ethoxynaphthalene, 2-methoxynaphthalene,
1-methoxy-4-(prop-1-enyl)benzene and
1-(cyclopropylmethyl)-4-methoxybenzene.
[0059] Topical skin care compositions of the present invention may
be divided into two classes of products, that is, cosmetic products
and topical washing products, and may include but is not limited to
antiperspirants, deodorants, day and night creams, shaving
products, hand creams, body lotions, hair shampoo and conditioners,
lipsticks, after-sun products, hand lotions, foundation creams,
moisturizing creams, skin food, skin tonics, skin lightening
products and overnight facial masks. The compositions may be in any
form. These forms may include lotions, creams, sticks, roll-on
formulations, mousses, aerosol sprays, pad-applied formulations,
powders, tonics, and emulsions (oil-in-water, water-in-oil, or
mixed emulsion systems).
[0060] The invention is now further described with reference to the
following non-limiting examples. All of the amounts are given as
percentage amounts by weight, unless otherwise indicated.
EXAMPLE 1
Screening for Compounds Protecting Keratinocytes against Irritating
Agents
[0061] Normal human epidermal keratinocytes (NHEK) were obtained
from skin biopsies and maintained as described by Rheinwald and
Green (cell, 6:331-344, 1975) in keratinocyte growth medium
supplemented with 10% heat inactivated fetal calf serum at a
humidity of 98% in a 5% carbon dioxide atmosphere. A confluent
culture was trypsinated and adjusted to a density of
5.times.10.sup.4 cells/ml. The cells were then seeded in the same
medium but with only 1% fetal calf serum in 24 well plates and
cultivated for a period of 48 h. A model irritating agent was then
applied to the cells by adding calcimycin to a final level of 2.5
.mu.M. The individual compounds, as listed below, dissolved in DMSO
were added simultaneously. The final concentration of the compounds
was 50 .mu.M or 10 .mu.M, the final DMSO concentration was adjusted
to 1% (v/v). Parallel treatments received no calcimycin
(non-irritated control) or calcimycin without compounds according
to the present invention (irritated control). The DMSO
concentration was adjusted to 1% in all these control treatments.
After 24 h incubation, the supernatant of the cells was harvested,
diluted 1:1 and added to an enzyme linked immunoassay kit for the
specific detection of prostaglandin E.sub.2 as a marker of cellular
irritation (Product # 404110, Neogen corporation, Lexington Ky.
40505, USA). The prostaglandin levels in treated cell cultures were
compared to the irritated and non-irritated control cultures in
order to determine the relative inhibition of PGE.sub.2 formation.
Results for the individual compounds are listed below.
TABLE-US-00001 relative inhibition in % of PGE.sub.2 formation in
keratinocyte cultures at Compound 50 .mu.M 10 .mu.M PEONILE .RTM.
(2-cyclohexylidene-2-phenylacetonitrile) 93.3 92.4 PROPYL DIANTILIS
90.9 95.1 (2-Ethoxy-4-(isopropoxymethyl)phenol) METHYL DIANTILIS
.RTM. n.d. 88.2 (2-Ethoxy-4-(methoxymethyl)phenol) Phenethyl
cinnamate 91.7 93.6 EUGENYL PHENYL ACETATE 96.6 99 (Phenyl
2-(4-allyl-2-methoxyphenyl)acetate) n-Hexyl salicylate 82.9 91.6
cis-3-Hexen-1-yl salicylate 94.8 81.4 Cyclohexyl salicylate 97.4
76.6 Amyl salicylate 89.8 73.5 Isobutyl salicylate 69.1 73.1
Phenethyl benzoate 92.4 56.9 TIGLATE BENZYLE (benzyl
2-methylbut-2-enoate) 72.4 50.2 CYCLAMEN ALDEHYDE .TM. 82.0 32
(2-Methyl-3-(4-isopropylphenyl)propanal) Isobutyl benzoate 52.5
n.d. Cinnamyl cinnamate 64.0 n.d. Phenethyl salicylate 50.9 n.d.
SILVIAL .RTM. 62.7 n.d.
(2-Methyl-3-(4-(2-methylpropyl)phenyl)propanal) ALISMONE .TM.
(2-heptylcyclopentanone) 92.4 47 NEROLINE .TM. CRIST
(2-ethoxynaphthalene) 83 50.2 YARA YARA .TM. (2-methoxynaphthalene)
78 46 ANETHOLE (1-methoxy-4-(prop-1-enyl)benzene) 51 n.d.
CENTIFOLYL .TM. (phenethyl pivalate) 39 n.d. TOSCANOL .RTM.
(1-(cyclopropylmethyl)-4-methoxybenzene) 56.7 n.d. Cinnamyl acetate
47.8 n.d. BOURGEONAL .TM. (3-(4-tert-butylphenyl)propanal) 65.0
n.d. ANATOLYL .TM. (phenethyl 2-methylbutanoate) 50.5 n.d.
Phenethyl isobutyrate 44.8 n.d.
2-Cyclopentylidene-2-phenylacetonitrile 80.8 71.1
3-Ethyl-2-phenylpent-2-enenitrile 73.2 63.9 n.d. = not
determined
[0062] Similar results as listed above were obtained by irritation
of the cells either by UVB irradiation or exposure to the skin
cells to irritating cationic surfactant benzalkonium chloride.
EXAMPLE 2
Fragrance Compositions with the Properties to Reduce or Suppress
the Formation of Skin Irritation
2.1 Floral Fragrance Composition No. 1
TABLE-US-00002 [0063] parts by weight 1/100 Peonile .RTM. 18.90
Alismone .TM. 5.30 Cyclohexyl salicylate 12.10 Silvial .RTM. 6.80
Toscanol .RTM. 0.15 Floral fragrance base 56.75
2.2 Floral Fragrance Composition No. 2
TABLE-US-00003 [0064] parts by weight 1/100 PEONILE .RTM. 1.00
PROPYL DIANTILIS 0.01 Phenethyl cinnamate 0.20 Hexyl salicylate
40.00 cis-3-Hexen-1-yl salicylate 1.00 Amyl salicylate 3.00
NEROLINE .TM. 0.10 Floral fragrance base 54.69
2.3 Floral-Fruity Fragrance Composition No. 3
TABLE-US-00004 [0065] parts by weight 1/900 Citronellyl acetate 10
Cyclamen aldehyde .TM.* 3 Ambrettolide
(oxacycloheptadec-10-en-2-one) 40 Ambrofix (CAS No. 6790-58-5) 10%
in dipropyleneglycol 8 Bourgeonal .TM.* 30 Centifolyl .TM.* 45
Dihydromyrcenol (2,6-dimethyloct-7-en-2-ol) 8 Ethyllinalool
(3,7-dimethyl-1,6-nonadien-3-ol) 45 Florol .RTM.
(tetrahydro-2-isobutyl-4-methyl-2H-pyran-4-ol) 25 Galaxolide .RTM.
(1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta- 12
gamma-2-benzopyran) 50% dissolved in isopropylmyristate Hedione
.RTM. (methyl 2-(3-oxo-2-pentylcyclopentyl)acetate) 250
Cis-3-hexenol 10% in dipropyleneglycol 3 Phenethyl isobutyrate* 25
Ethyl-2-methyl-butyrate 10% in dipropyleneglycol 3 Neroline .TM.*
10% in dipropyleneglycol 2 Orange essence brazil 15 Pomarose
(5,6,7-trimethylocta-2,5-dien-4-one) 10% in dipropyleneglycol 3
Prunella .RTM. subst (compounded perfumery base from Firmenich) 3
Cyclohexyl salicylate* 75 cis-3-Hexen-1-yl salicylate* 100 n-Hexyl
salicylate* 20 Phenylethyl salicylate* 80 Silvial .RTM.* 45
Tropional (2-methyl-3-(3,4-methylenedioxyphenyl)propanal) 40
Velvione .RTM. (5-cyclohexadecen-1-one) 10 All ingredients marked
with an * are active compounds having the ability to reduce or
suppress the formation of skin irritation, as defined according to
the present invention. The fragrance composition No. 3 comprises 47
weight % of actives.
2.4 Floral-Fruity Fragrance Composition No. 4
TABLE-US-00005 [0066] parts by weight 1/900 Benzyl-acetate 14
2-Phenylethanol 200 Cyclamen aldehyde .TM.* 3 Bourgeonal .TM.* 3
Centifolyl .TM.* 80 Phenethyl-cinnamate* 25 Citronellol 25
1-(1,1-Dimethoxypropan-2-yl)benzene 8 Dione
(2-[2-(3,3,5-trimethylcyclohexyl)- 3 1-ethanone]cyclopentanone) 10%
in dipropyleneglycol Dipropyleneglycol 128 Gardenol
(alpha-Methylbenzyl acetate) 5 Georgywood
(1-(1,2,3,4,5,6,7,8-octahydro- 2
1,1,7,8-tetramethyl-naphthalen-7-yl)ethanone) Geraniol 30 Hedione
.RTM. 70 Heliotropine 4 Indolene
(8-(1H-indol-2-yl)-8-(1H-indol-3-yl)- 1 2,6-dimethyloctan-2-ol)
Isoraldeine 70 (mixture of 4/1-(2,6,6-trimethyl-2- 25
cyclohexen-1-yl)-3-methyl-3-buten-2-one) Methyl diantilis .RTM.* 25
Neroline .TM.* 1 Patchouli essential oil rectified (origin:
Indonesia) 2 Peach pure (5-heptyl-dihydrofuran-2(3H)-one) 10
Pharaone (2-Cyclohexyl-1,6-heptadien-3-one) 8 1% in
dipropyleneglycol Pomarose 10% in dipropyleneglycol 3 Rose oxide 7
Cyclohexyl salicylate* 45 cis-3-Hexenyl salicylate* 55 n-Hexyl
salicylate* 20 Phenethyl salicylate* 80 Vanillin 5 Viridine
(phenylacetaldehyde dimethyl acetal) 3 Ylang Ylang essential oil 10
All ingredients marked with an * are active compounds having the
ability to reduce or suppress the formation of skin irritation, as
defined according to the present invention. The fragrance
composition No. 3 comprises 37.4 weight % of actives.
2.5 Fresh, Woody Floral Fragrance Composition No. 5
TABLE-US-00006 [0067] parts by weight 1/1000 Azurone 10% in
triethyl citrate 4
(7-(3-Methylbutyl)-2H-1,5-benzodioxepin-3(4H)-one) Ethyl vanilline
10% in DPG 4 Evernyl .TM. (methyl 2,4-dihydroxy- 2
3,6-dimethylbenzoate) Fixolide 55
(1-(3,5,5,6,8,8-hexamethyl-5,6,7,8-
tetrahydronaphthalen-2-yl)ethanone) Florhydral .RTM.
(3-(3-isopropylphenyl)butanal) 5 Iso E super .TM. 250
(1-(2,3,8,8-tetramethyl-1,2,3,4,5,6,7,8-
octahydronaphthalen-2-yl)ethanone) Kephalis 30
(4-(1-ethoxyvinyl)-3,3,5,5-tetramethylcyclohexanone) Cyclohexal 80
Linalool (3,7-dimethylocta-1,6-dien-3-ol) 40 Patchouli essential
oil 10 Peonil .RTM.* 100 Diethyl phthalate 60 Radjanol .TM.
(2-ethyl-4-(2,2,3-trimethyl- 50 3-cyclopenten-1-yl)-2-buten-1-ol)
Phenethyl salicylate* 100 cis-3-Hexen-1-yl salicylate* 55 n-Hexyl
salicylate* 55 Serenolide .TM. 60
(2-(1-(3,3-dimethylcyclohexyl)ethoxy)-2-methylpropyl
cyclopropanecarboxylate) Velvione .RTM. 40 All ingredients marked
with an * are active compounds having the ability to reduce or
suppress the formation of skin irritation, as defined according to
the present invention. The fragrance composition No. 5 comprises 31
weight % of actives.
2.6 Floral, Spicy, Green Fragrance Composition No. 6
TABLE-US-00007 [0068] parts by weight 1/948 Dimethyl benzyl
carbinyl acetate 25 Linalyle acetate 70 Phenylethyl alcohol 75
Methyl anthranilate 3 Cosmone (3-methylcyclotetradec-5-enone) 40
Florol .RTM. (2-isobutyl-4- 70 methyltetrahydro-2H-pyran-4-ol)
Galbanum oil 35 Gardenol 15 Hedione .RTM. 55 Indole 1% in
dipropyleneglycol (DPG) 45 Isoraldeine 70 80 Methyl diantilis
.RTM.* 45 Nirvanolide .TM. (13- 45
methyloxacyclopentadec-10-en-2-one) Peche pure 3 Peonile .RTM.* 55
EUGENYL PHENYL ACETATE* 20 Phenethyl salicylate* 100
Cis-3-Hexen-1-yl salicylate* 100 Vertofix coeur (methyl cedryl
ketone) 55 Ylang Ylang essential oil 12 All ingredients marked with
an * are active compounds having the ability to reduce or suppress
the formation of skin irritation, as defined according to the
present invention. The fragrance composition No. 6 comprises 33.7
weight % of actives.
2.7 Floral, Rosy, Fruity Fragrance Composition No. 7
TABLE-US-00008 [0069] parts by weight 1/825 Benzyl-acetate 20
2-Phenylethanol 200 Phenethyl benzoate* 130 Centifolyl .RTM.* 45
Cinnamyl cinnamate* 10 Phenyl ethyl cinnamate* 52 Citronellol 45
Dihydrofarnesal .TM. (3,7,11-trimethyldodeca-6,10- 20 dienal)
Florhydral .TM. (3-(3-isopropylphenyl)butanal) 3 Hedione .RTM. 150
Phenethyl isobutyrate* 25 Isoraldeine 70 45 Methyl diantilis .RTM.*
45 Peche pure 10 Rose oxide 10 Vanillin 15 All ingredients marked
with an * are active compounds having the ability to reduce or
suppress the formation of skin irritation, as defined according to
the present invention. The fragrance composition No. 7 comprises
37.2 weight % of actives.
EXAMPLE 3
Effect of Fragrance Compositions on Keratinocyte Cultures
[0070] Keratinocytes were grown in 24 well plates and irritated
with calcimycin as described in example 1. Fragrance compositions
of example 2 were dissolved in DMSO and added to the cultures
simultaneously. Inhibition of PGE.sub.2 formation was measured as
described in example 1. The results are listed in Table 1.
TABLE-US-00009 TABLE 1 Relative inhibition in % of PGE.sub.2
formation at different concentration of test fragrance 12.5 ppm
6.25 ppm Composition No. 1 79.0 42.4 Composition No. 2 82.6 85.6
Floral fragrance base 0 0
[0071] As can been seen from the figures in Table 1, about 80%
reduction of PGE.sub.2 formation was observed at 12.5 ppm if a
fragrance composition according to the present invention is
applied, whereas using the floral fragrance base without actives,
no measurable reduction of PGE.sub.2 formation was observed.
EXAMPLE 4
Irritation Reducing effects of a Hydrogel on Reconstituted
Epidermis
[0072] A hydrogel was prepared as follows:
TABLE-US-00010 INGREDIENT SUPPLIER INCI NAME % W/W CARBOPOL 980
Goodrich Carbomer 0.50 PEMULEN TR1 Goodrich Acrylate/C10-C30 0.20
Alkyl acrylate crosscopolymer LUBRAGEL CG Guardian
Polyglycerylmethacrylate & 0.50 Propylene glycol UCON 75H450
Amerchol PEG/PPG-17/6 copolymer 1.00 GLYCERIN AMI Glycerin 4.00
HEXYLENE GLYCOL Hexylene Glycol 2.00 DEIONISED WATER Water qsq
100.00 GERMALL 115 Sutton Imidazolidinyl Urea 0.60 SODIUM HYDROXIDE
Sodium Hydroxide qsp pH = 5.50 10% in water CREMOPHOR RH 40 BASF
PEG 40 Hydrogenated Castor oil 1.00 Glycerin and water were mixed,
Carbopol 980 was dispersed, then Pemulen TR 1 and then the
remaining ingredients were added.
[0073] Human reconstituted epidermis EpiDerm was purchased from
Mattek (Ashland, USA). The cultures were exposed to a single Dose
of 600 mJ UVB, and then either 50 mg phosphate buffered saline
(PBS) or 50 mg of the above hydrogel was added on top of the
individual EpiDerm cultures. After 24 h incubation, the culture
medium beneath the air exposed EpiDerm cultures was sampled and
analyzed for PGE.sub.2 as described in example 1. All skin samples
retained 100% cellular viability throughout the experiment. Skin
samples treated with a hydrogel containing the inventive perfume
composition 1 from example 2 suppressed UVB induced PGE.sub.2
formation.
TABLE-US-00011 TABLE 2 level PGE.sub.2 per ml t-test vs t-test vs
culture medium control UVB irritation Control, no UVB 8.253 1.000
UVB 600 mJ, PBS treatment 42.143 0.003 1.000 UVB 600 mJ, 48.778
0.046 0.742 Hydrogel treatment UVB 600 mJ, 12.135 0.384 0.001
Hydrogel containing 0.5% (w/w) fragrance comp. No. 1
EXAMPLE 5
Antiperspirant with Reduced Irritation on Reconstituted
Epidermis
[0074] An antiperspirant was formulated according the following
formulation:
TABLE-US-00012 Weight % Water 67 Aluminium chlorohydrate 20
Glycerin 5 Sunflower oil 4 Steareth 2 3 Steareth-20 1
[0075] The following antiperspirant compositions had been prepared:
[0076] I) antiperspirant & 1 weight % conventional perfume A
[0077] II) antiperspirant & 0.5 weight % conventional perfume B
[0078] III) antiperspirant & 0.5 weight % fragrance composition
No. 1 (Ex. 2.1) [0079] IV) antiperspirant & 1 weight %
fragrance composition No. 1 (Ex. 2.1)
[0080] 50 mg of the resulting antiperspirant I)-IV) or 50 mg of PBS
as control was added to Mattek skin cultures as described above,
and after 24 h the level of PGE.sub.2 in the culture medium was
determined according to the procedure described above. The results
are shown in Table 3.
TABLE-US-00013 TABLE 3 Level of PGE.sub.2 in t-test vs culture
medium control PBS 12.54 Composition I) 35.49 0.002 Composition II)
27.66 0.011 Composition III) 16.05 0.302 Composition IV) 9.48
0.368
[0081] As can be seen from the results above, antiperspirants
formulated with conventional perfumes (i.e. composition I) and II))
led to significantly enhanced PGE.sub.2 formation indicating an
irritating nature of these products to the human skin, whereas upon
treatment of EpiDerm with antiperspirants containing the inventive
fragrance composition, no significantly enhanced PGE.sub.2 levels
were detected. All epidermal cultures retained 100% of the cellular
viability showing that all the products are not cytotoxic.
* * * * *