Note: Descriptions are shown in the official language in which they were submitted.
CA 02501164 2005-03-17
NATURAL SUNLIGHT PHOTOSTABLE COMPOSITION
FIELD OF THE INVENTION
[0001] The field of invention of the present invention relates to photostable
compositions
that provide protection from ultraviolet radiation ("UVR"). The invention
particularly relates to
the sunscreens avobenzone, octocrylene and oxybenzone, forming a triplet
sunscreen
combination.
BACKGROUND OF INVENTION
[0002] It is well-documented that exposure to ultraviolet radiation ("UVR")
can result in
a wide range of adverse health consequences. Excessive exposure to UVB light
(290-320 nm)
can have both short and longer-term effects. The immediate and primary
consequence of
unprotected UVB exposure is erythema and sunburn Longer term, childhood
sunburns have
been correlated with melanoma later in life. UVA light (320-400 run)
penetrates deeper than
UVB, reaching both the epidermis and dermis. Repeated exposure to the shorter
wavelength
UVA II rays (approximately less than about 340 rim) and the longer wavelength
UVA I rays
(approximately longer than about 340 rim) have been associated with formation
of fine lines and
wrinkles, irregular skin pigmentation, weakening of the skin's immune system
and skin cancer.
Other skin disorders associated with overexposure to UVR include non-melanoma
skin cancers
(i.e., basal cell carcinomas and squamous cell carcinomas), actinic keratoses
and premature aging
of the skin.
[0003] Sunscreen products absorb a certain percentage of light over a
specified spectrum,
thus preventing potentially harmful erythemal UVR from reaching and damaging
the skin. The
sun protection factor ("SPF") listed on sunscreen products is related to this
percentage and is
intended to communicate the amount of erythemal UVR attenuation. More
particularly,
numerical SPF theoretically tells the user that he or she is protected X times
longer than without
sunscreen where X is the labeled SPF. For example, an SPF 33 product would,
theoretically,
absorb 97% of erythemal UVR and allow 3% of unattenuated light to reach the
skin. The user of
such an SPF 33 product would conclude that he or she could stay out in the sun
33 times longer
1
CA 02501164 2005-03-17
than without the sunscreen. However, because most sunscreens are not
photostable, labeled SPF
is not indicative of the photoprotection actually provided, and thus misleads
consumers to
believe that they can safely stay out in sun for longer periods of time than
that for which the
sunscreen actually provides protection. Accordingly, one objective of the
present invention is to
develop a photostable sunscreen whose labeling accurately communicates to
consumers the
degree of UVR protection actually provided. Another object of the invention is
to provide a
sunscreen composition that substantially maintains its SPF rating over an
exposure time period
of a typical consumer.
[0004) One shortcoming of currently available sunscreen products identified by
the
inventor is that SPF ratings are generated on the basis of sunscreen product
exposure to artificial
light spectra generated in a solar simulator. While convenient to the chemist
testing a
formulation, the SPF methodology does not satisfactorily provide an accurate
measure of how
the formulation will perform under actual conditions of use. Without being
bound by theory, the
deficiency is believed to be that wavelengths present in natural sunlight that
are missing in the
artificial spectra, or are present in much lesser relative amounts than in
natural sunlight, are
responsible (at least in part) for degradation reactions in many sunscreens.
These degradation
reactions result in lesser amounts of effective sunscreen being present over
the exposure time so
that effective SPF drops with exposure time. These degradation reactions also
generate free
radicals, which are associated with adverse health consequences.
[00051 The most commonly used simulator is a Xenon Arc solar simulator
equipped with
a WG320 filter, a UG11 filter, and a dichroic mirror. Such a simulator can
produce light spectra
meeting the SPF testing specifications set by the European Cosmetic Toiletry
and Perfumery
Association ("COLIPA") and routinely used in the US as a spectra standard for
SPF testing.
The same solar simulator using different filters can produce the Japanese
Cosmetic Industry
Association ("JCIA") test spectra and is used for the Persistent Pigment
Darkening ("PPD") in
vivo UVA protection test described below. Figure 1 compares the COLIPA and
JCIA spectra
with what is generally recognized worldwide as a standard sun spectra
(hereinafter "SSS") and is
based on average measurements at noon on June 20th at 40 N latitude.
2
CA 02501164 2007-11-22
100061 In contrast to SSS, the COLIPA and JCIA spectra produced in solar
simulators
eliminate infrared as well as visible light. As seen in Figure 1, a Xenon Arc
solar simulator cuts
off radiation at about 380 nm, meaning neither infrared nor visible radiation
are emitted.
Further, the filters used in solar simulator prevent wavelengths shorter than
about 290 nm from
being emitted. It has been reported that SPF values as tested in the solar
simulator are
significantly higher than those tested in actual sunlight. For these reasons,
the informational
value of SPF calculated on the basis of solar simulators is questionable. It
should be noted that
while the SSS curve of Figure 1 includes the light spectrum from infrared to
visible to
ultraviolet, it is an average spectra that varies throughout the year. Among
the factors
contributing to this variability are proximity and angle of the sun at
different latitudes and
altitudes at different times of day under variable atmospheric conditions
(e.g., cloud cover).
100071 The value of SPF as an accurate measure of protection from UVR has been
further called into doubt in the scientific literature. One internationally-
recognized authority in
the field of photobiology aptly titled a paper "Has SPF had its day?" Several
studies have shown
that sunburn is as likely to occur in users of high-SPF products than users of
no sunscreen at all.
Indeed, some researchers have suggested that use of sunscreen products
actually increases the
risk of developing malignant melanoma. Thus, there exists a long-felt, but as
yet unsatisfied
need for a sunscreen formulation that accurately communicates photoprotection
under actual
conditions of use for the entire period of exposure. This need is met by
present invention.
10008) Metrics other than SPF are available for indicating degree of
photoprotection
provided by sunscreens. With respect to UVA protection, two of the most common
test methods
are the in-vitro Boots Star System and the in-vivo PPD test. The Boots Star
System, based on
instantaneous readings from a spectrophotometer, indicates the ratio of the
average absorbance
of UVA energy to UVB energy. A single star is assigned fora UVA/UVB ratio of
0.2 - 0.4.
Two and three stars are assigned to products where the UVA/UVB ratios is 0.4 -
0-6 and 0.6 -
0.8, respectively. Four stars are assigned to products with a UVA/UVB ratio of
greater than 0.8.
PPD measures skin darkening two to four hours after exposure to UVR. A solar
simulator
emitting a spectra defined by the JCIA is used for the PPD test. However, the
degree to which
CA 02501164 2007-11-22
PPD reflects photoprotection under actual conditions of use is limited by the
artificial nature of
the light source.
100091 Broad-spectrum sunscreens were developed to absorb both UVA and UVB
energy. To achieve coverage over the UVA and UVB spectra, multiple sunscreens
are selected
both on the basis of absorbed wavelength range as well as other properties
(i.e., water resistance,
hypoallergenicity). A prevailing paradigm in sunscreen formulation has been
"more is better".
Many follow the approach that high SPF or more Boots stars can best be
achieved by including
many sunscreens in high concentrations. Because many sunscreens have decreased
performance
characteristics (e.g., lower SPF) when exposed to natural light, adherents of
this school of
formulation add more sunscreen actives than should theoretically be required
to achieve a certain
SPF. In so doing, they compensate for the degradation that takes place in the
laboratory setting.
However, this reasoning is flawed. There is markedly more photodegradation in
natural sunlight,
causing the actual SPF realized by the consumer to be lower.
100101 The "more is better" paradigm also overlooks the fact that among the
degradation
products in photolabile sunscreens are free radicals which can cause damage to
DNA and other
cellular molecules. Over time, free radical damage may become irreversible and
lead to disease
including cancer. Moreover, to the extent that a sunscreen is photolabile
under artificial light
(e.g., JCIA, COLIPA), that same composition could undergo more
photodegradation, and
produce more free radicals, when exposed to UVR as well as infrared and
visible light under
ambient conditions. Thus, a third objective of the present invention is to
identify a combination
sunscreen composition where after irradiation under ambient light each
sunscreen active is
photostable and thereby minimize the formation of potentially harmful free
radicals.
100111 Avobenzone, which absorbs both UVA I and II is among the more commonly
used UVA sunscreens and has been used in combination with other sunscreens in
several
commercial products. For example, BullfrogTM`' Sunscreen SPF 15 AmphibiousTM
Formula was
commercially available in the 1980s and contained 2% (wt/wt) avobenzone, 10%
(wt/wt)
octocrylene, and a third sunscreen, ethyl dihydroxypropyl aminobenzoate. Shade
UVAGuard
(Schering-Plough HealthCare Products) was sold in the US in 1993 and contained
3% (wt/wt)
4
CA 02501164 2007-11-22
avobenzone, 3% (wt/wt) oxybenzone, and a third sunscreen, 7.5% (wt/wt)
octylmethoxycinnamate. OmbrelleTM SPF 30 (L'Oreal), sold in Canada, contained
3%
avobenzone (wt/wt), 10% octocrylene (wt/wt) and two additional sunscreens, 6%
oxybenzone
(wt/wt) and 5% octisalate (wt/wt). Avobenzone has not, however, been combined
in a sunscreen
formulation as claimed in the present invention (i.e., with octocrylene,
oxybenzone and no
substantial amounts of additional photodegradable sunscreens, preferably
substantially no
additional sunscreens).
100121 After recognizing the importance of broad spectrum coverage, sunscreen
research
began to focus on the effectiveness and efficiency of the protection provided.
One particularly important parameter that has emerged is photostability. In
published articles
and meetings of national and international Societies of Cosmetic Chemists,
researchers have
commented that for maximum safety, broad-spectrum protection must remain
efficient
throughout the period of exposure to the sun. Many tests for photostability
have been proposed.
Of these, the majority are performed using artificial light sources (e.g.,
COLIPA, JCIA). For the
reasons discussed above with respect to SPF and UVA protection testing, use of
artificial light
can strongly confound test results.
100131 Diffey et al. "Sunscreen Product Photostability: A Key Parameter for a
More
Realistic In Vitro Efficacy Evaluation" Bur. J. Dermatol. 7: 226-228 (1997)
proposes a photostability test where thin films of sunscreen product are
scanned. UVA and UVB
absorbance are plotted before and after irradiation, and the change in the
area under the curve
represents relative photostability. The Diffey protocol has several
limitations. First, the sample
area to be scanned by most instruments is very small, making it difficult to
ascertain whether the
same area was scanned before and after irradiation. If pre- and post-
irradiation scans are not
taken over precisely the same area, variations in film thickness will skew the
results. Moreover,
where a composition contains several sunscreens, it is impossible to determine
the extent of
change for any one sunscreen. This is important because a photolabile
sunscreen may undergo
significant free radical and/or chemical entity change that could go
undetected by the Diffey test.
CA 02501164 2005-03-17
[0014] In U.S. Patent Application Publication Nos. 2004/0047818 and
2004/0047817,
Bonda et al. describe a test protocol very similar to Diffey, except that
photostability is judged
based on absorbance at wavelength(s) of particular interest. This protocol
shares the same
limitations as Diffey. Further, by limiting the test spectra to artificial
light at a specific
wavelength, the Bonda proposed method may be even less predictive of
photostability than that
of Diffey.
[00151 Berset et al. "Proposed Protocol for Determination of Photostability
Part 1:
Cosmetic UV Filters." Intl. J. Cosmet. Sci., 18(4): 167-177 (1996) teaches a
photostability
protocol based on comparison of UVR absorption of individual sunscreen actives
in solution
before and after irradiation. As discussed above, commercially-available,
broad spectrum
sunscreens contain multiple sunscreen actives as well as other ingredients,
the interaction of
which may or may not destabilize the composition. Since the Berset method does
not account
for these interactions, it is not sufficiently predictive of the
photostability.
[0016] A more accurate approach to quantifying photodegradation, one which
would
account for production of free radical intermediates, is to analyze the
content of individual
sunscreen actives in the final commercial product before and after
irradiation. Cambon et al.
"An In-Vivo Method to Assess the Photostability of UV filters in a Sunscreen"
J. Cosmet. Sci.,
52: 1-11 (2001) describes a method of measuring photodegradation of sunscreen
product that has
been directly applied to the skin of human subjects. After irradiation with
artificial light (i.e., a
solar simulator), residual product is removed via tape strippings, and assayed
with HPLC. The
use of HPLC produces a true assessment of photodegradation of a sunscreen on
exposure to the
wavelengths tested. Because the light source used in the Cambon protocol is a
solar simulator
(i.e., as opposed to natural light), its predictiveness of photostability is
limited. Moreover, the
ability to control the thickness of application of sunscreen formulation to
human skin in a
uniform manner is inherently limited, and the absorption of different
formulation components in
different compositions may vary from subject to subject, with respect to both
the sunscreen
active and the various excipients, thereby confounding comparisons between
tests made on
different subjects, at different times, or with different formulations.
6
CA 02501164 2005-03-17
[0017] As discussed above, avobenzone's broad coverage in the UVA I and UVA II
spectra make it a desirable sunscreen. However, avobenzone is widely
recognized to be
photolabile and to undergo significant photodegradation. For example, as shown
in Tables 7 and
8 below, significant percentages of avobenzone were lost when a popular,
commercially-
available sunscreen product sold in the US and labeled as having an SPF of 30
was exposed to
natural sunlight. In a search for photostable broad spectrum sunscreens,
researchers have
attempted to combine avobenzone with other sunscreens. USPN 5,576,354
(assigned to L'Oreal)
claims a process for stabilizing avobenzone with respect to UV radiation of
wavelengths between
280 and 380 nm by adding octocrylene, a UVB absorber, to a sunscreen having 1%
to 5%
(wt/wt) avobenzone, to result in a concentration of at least 1% octocrylene
(wt/wt based on the
sunscreen composition). USPN 5,776,439 discloses a photostable composition
comprising from
I% to 10% (wt/wt) avobenzone and from 0.5% to 10% oxybenzone, a UVB absorber.
[0018] Published U.S. Patent Application No. 2004/0047818 (Bonda et al.)
discloses a
sunscreen composition comprising avobenzone, less than 1% octocrylene (wt/wt),
and a diester
or polyester of naphthalene dicarboxylic acid. The Bonda 2004/0047818
application further
teaches the three sunscreens in further combination with oxybenzone. However,
none of these
putatively stable prior art compositions teach a sunscreen combining
avobenzone, octocrylene
and oxybenzone alone, with no substantial amount of other photodegradable
sunscreen actives or
with substantially no other sunscreen active present.
[0019] Published U.S. Patent Application No. 2004/0166070 (Galdi et al.)
discloses non-
pilling UV-photoprotecting alcoholic sunscreen gels comprising acrylates/C12-
22
alkylmethacrylate copolymer and an effective amount of at least one UV-A
and/or UV-B
screening agent where the screening agent comprises avobenzone, octocrylene,
oxybenzone
and/or octyl salicylate. Lower monohydric alcohols, most commonly ethanol and
isopropanol,
are used in alcohol sunscreen gel compositions. Example 1 of the Galdi
Application discloses an
ethanolic sunscreen gel containing acrylates/C12.22 alkylmethacrylate
copolymer in combination
with four sunscreens (avobenzone, octocrylene, oxybenzone and octyl
salicylate). The present
invention does not contain one or more elements of the sunscreen composition
disclosed in the
Galdi Application, including, but not limited to, the following:; (i) the
present invention may be
7
CA 02501164 2005-03-17
essentially free of lower monohydric alcohols or free of lower monohydric
alcohols; (ii) the
present invention may be a sunscreen formulation that is essentially free of,
or free of,
acrylates/C12.22 alkylmethacrylate copolymer in an effective non-pilling
amount used to thicken
(i.e., gel) a low molecular weight alcohol (i.e., C1-C4 alcohol); and (iii)
compositions of the
present invention do not include octyl salicylate (also known as octisalate)
which, as discussed
below, is not photostable.
[00201 Published U.S. Patent Application No. 2005/0013781 (Dueva-Koganov)
discloses
photoprotective compositions comprising one or more sunscreens and one or more
"optimizing
agents" which are defined as diols, alcohols, glycols, polyhydric alcohols as
well as derivatives
or combinations thereof that optimize SPF, Protection Factor A, Boots Star
Rating, polarity,
critical wavelength or photostability (or any combinations of the foregoing)
of the oil phase,
water phase, both phases of the composition, or the final sunscreen
formulation. Polyhydric
alcohols, in particular certain glycols, disclosed in the Dueva-Koganov
Application as
"optimizing agents" are as follows: pentylene glycol (1,2-pentanediol),
neopentyl glycol
(neopentanediol), caprylyl glycol (1,2-octanediol), ethoxydiglycol, butylene
glycol
monopropionate, diethylene glycol monobutyl ether, PEG-7 methyl ether,
octacosanyl glycol,
arachidyl glycol, benzyl glycol, cetyl glycol (1,2-hexanediol), C14_18 glycol,
C15_18 glycol, lauryl
glycol (1,2-dodecanediol), butoxydiglycol, 1,10-decanediol, ethyl hexanediol,
and combinations
thereof.
100211 The Dueva-Koganov Application discloses over thirty sunscreens,
including
avobenzone, octocrylene and oxybenzone. Table 21 discloses a composition
comprising five
sunscreens (homosalate, octyl salicylate, oxybenzone, octocrylene and
avobenzone) in
combination with two optimizing agents (1,2-octanediol and neopentyl glycol).
The present
invention does not contain one or more elements of the sunscreen composition
disclosed in the
Dueva-Koganov Application, including, but not limited to, the following:
Embodiments of the
present invention are substantially free of substantial amounts of optimizing
agents, preferably
substantially free of optimizing agents, and more preferably free of
optimizing agents. In
addition, as discussed below, both homosalate and octyl salicylate are not
photostable, and
compositions containing these sunscreens are not within the scope of the
present invention.
8
CA 02501164 2007-11-22
[00231 The present invention is an improvement of pending U.S. Patent
Application
Serial No. 10/887,464, now Publication No. 2005/0025727. By identifying
combination
sunscreen product, the present invention meets two long felt but unmet needs:
(i) accurately
communicating the amount of UVR photoprotection actually provided; and (ii)
minimizing the
amount of potential harmful free radicals formed as byproducts of
photodegradation.
BRIEF DESCRIPTION OF THE INVENTION
100241 The present invention is a novel, photostable composition that protects
the skin
and other substrates and products against ultraviolet light rays comprising a
triplet combination
of three sunscreens (avobenzone, octocrylene and oxybenzone) that is
substantially free of
substantial amounts of optimizing agents. Sunscreens of the present invention
can be
essentially free of lower rnonohydric alcohol or free of lower monohydric
alcohol. Sunscreens
of the present invention can also be essentially free of, or free of,
acrylates/C12-22
alkylmethacrylate copolymer in an effective non-pilling amount used to thicken
(i.e., gel) a low
molecular weight alcohol. Compositions of the present invention provide an SPF
of X and none
of the three required sunscreen actives photodegrade to a concentration of
less than Z, where Z is
70%, preferably 75%, and more preferably 80% of their initial concentration
after exposure to Y
SEDs of UVR from natural sunlight, where Y is about Y2 X, to a maximum of
about 15.
Optionally, compositions of the present invention may include one or more
photostable
sunscreens (other sunscreens that do not degrade below a concentration Z as
defined above) that
do not substantially negatively impact the photostability of the triplet
sunscreens. Compositions
of the present invention are substantially free of substantial amounts of both
other
photodegradable sunscreens and optimizing agents, preferably substantially
free of both other
photodegradable sunscreens and optimizing agents, more preferably completely
free of both
other photodegradable sunscreens (especially octinoxate, octisalate and
homosalate) and
9
CA 02501164 2005-03-17
optimizing agents. Compositions of the present invention are even more
preferably substantially
free of substantial amounts of all other sunscreens, still more preferably
substantially free of all
other sunscreens, and yet more preferably completely free of all other
sunscreens.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] Figure 1 shows COLIPA, JCIA and SSS spectra.
DETAILED DESCRIPTION OF THE INVENTION
[0026] The present invention relates to a novel, photostable sunscreen
composition that
provides and substantially maintains a desired SPF of X throughout the period
of exposure to
natural sunlight and comprises a triplet combination of three sunscreen
actives - avobenzone,
octocrylene and oxybenzone) that is substantially free of substantial amounts
of optimizing
agents. Each of the three required sunscreen actives photodegrades to a
concentration of not less
than 70%, preferably not less than 75%, and more preferably not less than 80%
of their initial
concentration after exposure to Y SEDs of UVR from natural sunlight, where Y
is about' AX, to
a maximum of 15. Sunscreens of the present invention can be essentially free
of lower
monohydric alcohol or free of lower monohydric alcohol. For purposes of the
present invention,
"lower monohydric alcohol" means methanol, ethanol, propanol and isoproponal,
or mixtures
thereof. Sunscreens of the present invention can also be essentially free of,
or free of,
acrylates/C12_22 alkylmethacrylate copolymer in an effective non-pilling
amount used to gel a C1-
C4 alcohol.
[0027] Optionally, compositions of the present invention may contain a fourth
sunscreen
component selected from the group consisting of one or more sunscreens that
are (i) individually
photostable (i.e., and do not photodegrade to a concentration of less than
70%, preferably not
less than 75%, more preferably not less than 80% of their initial
concentration after exposure to
Y SEDs of UVR from natural sunlight, where Y is about V2 X) and (ii) do not
substantially
negatively impact the photostability of the sunscreens in the triplet
combination. For purposes of
the present invention, "substantially negatively impacts" means reducing the
residual percentage
CA 02501164 2005-03-17
of any of avobenzone, oxybenzone or octocrylene to less than Q, where Q is
70%, preferably
75%, more preferably 80%, still more preferably 85%, even more preferably 90%
and most
preferably 95% of the initial concentration of that particular sunscreen
component. In a further
preferred embodiment of the present invention, "substantially negatively
impacts" means
reducing the residual percentage of any individual component of the triplet
combination by more
than 5% based the original concentration of the individual component. Residual
percentage is
determined by HPLC.
[0028] Compositions of the present invention are substantially free of
substantial
amounts of photodegradable sunscreens, preferably substantially free of
photodegradable
sunscreens, and more preferably substantially free of substantial amounts of
all other sunscreen
actives, most preferably completely free of other sunscreen actives. For
purposes of the present
invention, "substantially free" means less than 5%, preferably less than about
4'/2%, more
preferably less than about 3%, and most preferably completely free of other
sunscreen actives.
For purposes of the present invention, a "photodegradable sunscreen" includes,
but is not limited
to, a sunscreen active ingredient selected from the group consisting of
aminobenzoic acid,
cinoxate, homosalate, menthyl anthranilate, octyl methoxycinnamate,
octisalate, padimate 0, and
trolamine salicylate. While not photodegradable as defined above, the pigments
zinc oxide and
titanium dioxide are generally undesirable for inclusion in compositions of
the present invention.
Zinc oxide and titanium dioxide will be grouped with the photodegradable
sunscreens with
respect to allowable content in compositions of the invention (i.e.,
"substantially free of
substantial amounts of ..." or "completely free of ...").
[0029] Compositions of the present invention are also substantially free of
substantial
amounts of optimizing agents. Examples of optimizing agents are 1,2-
pentanediol,
neopentanediol, 1,2-octanediol, ethoxydiglycol, butylene glycol
monopropionate, diethylene
glycol monobutyl ether, PEG-7 methyl ether, octacosanyl glycol, arachidyl
glycol, benzyl glycol,
1,2-hexanediol, C14_18 glycol, C15_18 glycol, 1,2-dodecanediol,
butoxydiglycol, 1,10-decanediol,
ethyl hexanediol, as well as combinations thereof. Preferably compositions of
the present
invention are substantially free of optimizing agents, and more preferably
completely free of
optimizing agents.
11
CA 02501164 2011-04-26
[0030] Sunscreen compositions of the present invention unexpectedly have been
found to
maintain substantially an SPF of X throughout the period of exposure and to be
photostable
when irradiated with natural sunlight, irrespective of altitude, season, time
of day, angle of the
sun relative to the sample or atmospheric conditions (e.g., cloud cover). Each
sunscreen active
in the triplet combination of the present invention does not photodegrade to
less than about 70%,
preferably not less than about 75%, and more preferably not less than about
80% of its initial (i.e.
pre-natural UV light exposure) concentration after exposure to Y SEDs of UVR
from natural
sunlight, where Y is about Y2 X, to a maximum of about 15. For purposes of the
present
invention, "pre-natural UV sunlight exposure" is intended to mean the
composition just prior to
being exposed to natural sunlight in a laboratory test or in actual consumer
use (i.e., in the
ambient environment). Incidental UV exposure in the course of manufacture and
packaging of
the composition is to be neglected.
(00311 The ratio (weight/weight) of avobenzone: oxybenzone: octocrylene should
preferably be in the range of a : b : c, where a is from 0.5 to 5.0, b is from
0.5 to 10, and c is from
0.5 to 10, preferably a is from 1 to 3, b is from I to 6, and c is from 1 to
10. Once a proper ratio
is selected, the sunscreen actives can be combined in sufficient amounts to
achieve a desired SPF
using standard formulating techniques known to persons of ordinary skill in
the art.
[0032] Avobenzone, the USAN name for butylmethoxydibenzoylmethane, is sold
under
various tradenames including ParsolTM 1789, ParsolTM, EusolexTM 9020, Neo
HeliopanTM 357, PhotoplexTM,
UvinulTM BMBM. Other chemical names for avobenzone include: 1-(4-
methoxyphenyl)-3-(4-tert-
butylphenyl) propane-l,3-dione; 1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)
propane- 1,3-dione;
4-(1, 1 -dimethylethyl)-4'-methoxydibenzoylmethane; 4-methoxy-4' -tert-
butyldibenzoylmethane;
and 4-tert-butyl-4'-methoxydibenzoylmethane.
[0033] Oxybenzone, also known as benzophenone-3, is sold under various
tradenames
including AduvexTM 24, AdvastabTM 45, AnuvexTM, ASL 24, ChimassorbTM 90,
CyasorbTM UV 9 Light
Absorber, CyasorbTM UV 9, EscalolTM 567, Neo HeliopanTM BB, NSC 7778,
Ongrostab HMB, Onzone,
Seesorb 101, Spectra-Sorb UV 9, Sumisorb 110, Syntase 62, TinosorbTM B 3,
UvasorbTM Met/C,
12
CA 02501164 2011-04-26
UvinulTM M 40, UvinulTM 3040, UvinulTM 9, UvistatTM 24, and Viosorb 110. Other
chemical names for
oxybenzone include: (2-hydroxy-4-methoxyphenyl) phenylmethanone; 2-benzoyl-5-
methoxyphenol; 2-hydroxy-4-methoxybenzophenone; and 4-methoxy-2-
hydroxybenzophenone.
100341 Octocrylene is sold under various tradenames including Agent AT 539,
"Eusolex TM
OCR, Neo HeliopanTM 303, SanduvorTM 3039, UvinulTM N 539, UvinulTM N 539SG,
UvinulTM N 539T,
UvinulTM 3039, Viosorb 930. Other chemical names for octocrylene include: 2-
cyano-3,3-
diphenylacrylic acid 2-ethylhexyl ester 2-ethylhexyl a-cyano-/3-
phenylcinnamate; 2-ethylhexyl
a-cyano-f3, fl'-diphenylacrylate; 2-ethylhexyl 2-cyano-3,3-diphenyl-2-
propenoate; 2-ethylhexyl
2-cyano-3,3-diphenylacrylate; 2' -ethylhexyl 2-cyano-3-phenylcinnamate.
100351 As described above, a sunscreen composition of SPF X is considered to
be
"photostable" when at least 70%, preferably at least 75%, more preferably at
least 80% of each
sunscreen active in the composition remains after exposure of the composition
to Y SEDs of
natural sunlight, where Y is about'/z X, to a maximum of about 15.
"Photostability" is assessed
by (i) assaying the pre-UVR exposure concentration of each sunscreen active
present in the
sunscreen composition by high-performance liquid chromatography ("HPLC"); (ii)
applying a
sample of the sunscreen composition at a concentration of 2 mg/cm2 (a standard
concentration
used in SPF testing) to a non-coated microscope slide or similar non-reactive
surface (e.g., glass
or quartz plate); (iii) irradiating the sample in natural sunlight according
to a dosing regimen as
illustrated in Table 1; (iv) assaying the concentration of each sunscreen
active post-UVR
exposure.
Table 1 - Dosing Regimen
SPF SEDs Irradiated
1 2 4 8 16
2 x
4 x x
8 x x x
16 x x x x
>30 x x x x x
13
CA 02501164 2005-03-17
[0036] More specifically, after the desired UVR exposure, each slide is
removed from
sunlight and placed in a sealed Blue MaxTM polypropylene conical tube (Becton
Dickinson) or
similar container, and stored in an area to prevent further exposure to
natural sunlight. When an
irradiation series is completed, the residual content of each sunscreen active
is determined via
HPLC, such as the Perkin Elmer Model 200, equipped with a 785 UV/V detector,
and a C18
column. A detector wavelength of 31.0 nm and an eluent solution of 85/15
phosphoric acid
solution may be used. The sunscreen composition is extracted from the slide
with isopropanol or
other suitable solvent and sonicated for a minimum of 10 minutes to completely
solubilize the
sunscreen actives. The solution is then filtered with a .45 um GHP13 mm
syringe filter. The
above analytical procedure may be modified in a manner that would be obvious
to the person of
ordinary skill in the art.
[0037] Based on the above analytical method, surprisingly it has been
discovered that
many sunscreen actives reported to be photostable based on laboratory tests
using artificial
sunlight sources (e.g., COLIPA, JCIA spectra) are in fact photodegradable when
exposed to
natural sunlight.
[0038] Because the sunscreen compositions of the present invention are
photostable,
lesser amounts of sunscreen actives are needed to obtain an SPF. For purposes
of the present
invention "sunscreen efficiency" is expressed by the ratio SPF/total sunscreen
active % (wt/wt).
The sunscreen compositions of the present invention have a sunscreen
efficiency greater than 2,
preferably at least about 3 , and more preferably at least about 4. Table 2
compares the
sunscreen efficiencies of commercial products with those of the invention. The
SPF 70 product
of the invention had a sunscreen efficiency more than 2 V2 times greater than
a comparable
commercial SPF 70 product.
14
CA 02501164 2005-03-17
Table 2 - Comparative Sunscreen Efficiency
Sunscreen Composition % Sunscreen Sunscreen
Efficiency
Commercial SPF 30 17.5 1.71
Commercial SPF 40 26.5 1.51
Commercial SPF 50 33.5 1.49
Commercial SPF 70 35.5 2.00
Invention SPF 30 7.5 4.00
Invention SPF 60 13 4.61
Invention SPF 70 13 5.38
[0039] Apart from formulating efficiencies, the photostability of compositions
of the
present invention imparts another benefit - minimizing the formation of
potentially harmful free
radicals (i.e., in photodecay products). First, since individual sunscreen
actives are used in
smaller quantities, lesser amounts of photoreactive sunscreens are available
to form free radicals.
Relatedly, as a consequence of their photostability, compositions of the
present invention can be
applied less frequently, again minimizing potential free radical formation.
[0040] Photoprotective compositions of the present invention may be prepared
according
to principles and techniques generally known to those skilled in the cosmetic
and pharmaceutical
arts. Octocrylene and oxybenzone are added under heat to a cosmetically
acceptable vehicle and
mixed until homogeneous. Avobenzone is then added to this mixture.
Cosmetically acceptable
vehicles useful for preparing compositions of the present invention are well-
known to persons of
ordinary skill in the art and include lotions, creams, sprays, gels, wax-type
sticks, oils, milks and
mousses. Such vehicles can be emulsions of the water-in-oil, oil-in-water or
water-in-silicone
types. The vehicle contains one or more diluents well-known to persons of
ordinary skill in the
art including, but not limited to, rheology modifiers, emulsifiers, pH
modifiers, moisturizers
(e.g., aloe extract), humectants, emollients (e.g., caprylic/capric
triglycerides), structuring agents
CA 02501164 2007-11-22
(e.g., beeswax, candelilla wax, paraffin), stabilizers, lubricants,
fragrances, preservatives (e.g.,
propylparaben), colored pigments or coloring agents. Typical, non-limiting
composition
vehicles and excipients can also be found in the following US patents,
4,015,009; 4,024,106;
4,455,295; 4,613,499; 4,710,373; 4,863,963; 5,160,731; 5,338,539; 5,426,210;
5,783,173; and 5,917,088.
100411 The following examples are further illustrative of the present
invention. The
components and specific ingredients are presented as being typical, and
various modifications
can be derived in view of the foregoing disclosure within the scope of the
invention.
EXAMPLE 1 - Sunscreen Comparison
100421 Formulation 1, a photostable sunscreen composition with an SPF of 50,
was
prepared according to the procedure set forth below.
Formula I* Formula 2 Formula 3
(Invention) (Comparison) (Comparison)
Phase A
Ozokeritc 9 9 9
Beeswax 6 6 6
Candelilla Wax 4 4 4
Paraffin 9 9 9
Octocrylene 10 1.6 10
Oxybenzone 6 6 6
Aloe Extract 0.0823 0.1 0.1
Homosalate ---- 15 15
Octisalate ---- 5 5
Octinoxate ---- 7.5 7.5
Caprylic/Capric
Triglycerides 9 9 6.8
Diisobutyl Adipate 15 6 5
Silica 2 2 1.5
Flora/Nut Extracts 0.1 0.1 0.1
16
CA 02501164 2005-03-17
Vitamins A,C & E 0.01 0.01 0.01
Propylparaben 0.1 0.1 0.1
BHT 0.01 0.01 0.01
Hexacaprylate/
Hexacaprate 14.58 4 2.88
Vitamin E 0.00154 ---- ----
Mineral Oil 0.00123 ---- ----
Avobenzone 3 2 2
Phase B
Fragrance 0.11462 ---- ----
Cyclomethicone 12 13.58 10
*Unless otherwise stated, percentages are weight/weight.
With the exception of the avobenzone, combine the ingredients of Phase A and
mix until
uniform. Add avobenzone. Continue mixing at about 75 C until a uniform fluid
mixture is
obtained. Cool while stirring. At about 50 C add the Phase B ingredients.
Continue mixing and
cool to about 40 C.
[00431 To compare the photostability of Formulas 1 and 2, a uniform 2 mg/cm2
film of
sunscreen product was placed on multiple microscope slides. The slides were
exposed to direct
sunlight for time intervals corresponding to 1, 2, 4, 8, and 16 SEDs as
measured by a Solar Light
PMA 2100 detector. (Unless otherwise indicated, all sunlight exposures were in
Ormond
Beach, Florida). Slides were removed from the sun after the desired exposure
and stored in Blue
MaxTM polypropylene conical tubes. Upon completion of the test series, samples
were dissolved
in a suitable solvent, sonicated and then assayed via HPLC. Residual
avobenzone content is
reported as a percentage of sunscreen remaining after UVR exposure is
presented in Table 3.
Unless otherwise indicated, all assays were performed by HPLC with oxybenzone,
if present, as
the internal standard.
17
CA 02501164 2005-03-17
Table 3 - Residual Avobenzone
Formula 2 Formula 2
SEDs Formula I (Trial 1) (Trial 2) Formula 3
1 100% 73% 95% 69%
2 100% 42% 90% 57%
4 99% 33% 79% 35%
8 96% 19% 64% 25%
16 94% ---- 42% ----
[00441 Residual concentration of avobenzone, octinoxate, and octisalate in
Formula 2
was further investigated by exposing samples to natural sunlight at various
hours in the day and
times of the year, as well as to artificial spectra. The results are presented
in Tables 4, 5 and 6.
Table 4 - Formula 2 (Residual % of Avobenzone)
SEDs COLIPA JCIA 2/25 3/31 4/17 5/5 5/20 5/28* 5/18a 7/6a
---- 89% 73% 67% 73% 92% 95% 75% 80% 89%
2 99% 80% 48% 48% 42% 85% 90% 70% 73% 78%
4 96% 58% ---- 35% 33% 78% 79% 60% 60% 65%
8 89% 58% ---- 25% 19% 62% 64% 29% 44% 55%
16 77% ---- ---- ---- ---- 45% 42% 19% 26% 21%
Table 5 - Formula 2 (Residual % of OMC)
SEDs COLIPA JCIA 2/25 3/31 4/17 5/5 5/20 5/28* 5/18a 7/6a
1 ---- 78% 60% 57% 61% 66% 69% 61% 63% 66%
2 78% 72% 51% 51% 46% 61% 63% 58% 60% 59%
4 69% 59% ---- 42% 43% 59% 58% 53% 54% 54%
8 64% 61% ---- ---- 28% 52% 52% 42% 49% 49%
16 58% ---- ---- ---- ---- 46% 45% 37% 41% 35%
18
CA 02501164 2005-03-17
Table 6 - Formula 2 (Residual % of Octisalate)
SEDs COLIPA JCIA 2/25 3/31 4/17 5/5 5/20 5/28* 5/18a 7/6a
1 99% 98% 99% 96% 97% 96% 84% ---- 98% 97%
2 100% 97% 95% 97% 91% 95% 94% 77% 98% 96%
4 99% 97% ---- 96% 87% 88% 89% 74% 96% 94%
8 99% 97% ---- ---- 83% 79% 81% 59% 93% 91%
16 98% ---- ---- ---- ---- 64% 68% 52% 90% 76%
* Irradiated over 3 days in early morning sun.
a Tests conducted in 2004. Other tests were conducted in 2003.
[00451 The photodegradation of avobenzone (as expressed as a residual
percentage) was
further studied by comparing Formula 1 with a popular, commercially-available
sunscreen
product sold in the US and labeled as having an SPF of 30. This "Commercial
30" product is an
oil-in-water emulsion with sunscreen actives listed on the label and assayed
to be approximately
3% oxybenzone, 2% avobenzone, 7.5% OMC, 5% octisalate, and 7 % homosalate. The
Commercial 30 product as tested on two dates (Trials 1 and 2) is presented in
Table 7 below.
Table 7 - Percent Residual Avobenzone
SEDs Commercial 30 Formula 1
(Trial 1) (Trial 2)
1 25% 74% 100%
2 7% 60% 100%
4 3% 41% 99%
8 0% 19% 96%
16 ---- 6% 94%
Exposure Date for Trial 1: 4/7/03
Exposure Date for Trial 2: 5/7/03
Exposure Date for Formula 1: 5/7/03
19
CA 02501164 2005-03-17
EXAMPLE 2 - Sunscreen Comparison
100461 The trio of sunscreens of the present invention - octocrylene,
oxybenzone and
avobenzone - were combined in a prior art sunscreen formulation in the
following weight/weight
ratios: 10% octocrylene, 6% oxybenzone, 3% avobenzone and 5% octisalate. Two
formulations, the trio sunscreens of the present invention (Formula 4) and the
prior art quartet
of sunscreens (Formula 5), were prepared according to the procedure set forth
below.
Ingredients Formula 4 Formula5 Ingredient
(Invention) (Prior art) Function
Phase A
Microcrystalline Wax 0.5 0.5 Thickener
Polyethylene, Stearoxy Dimethicone 0.5 0.5 Thickener
Beeswax 0.5 0.5 Thickener
Cetyl Dimethicone 0.5 0.5 Solvent
Oxybenzone 6.0 6.0 Sunscreen
Octocrylene 10.0 10.0 Sunscreen
Octisalate ---- 5.0 Sunscreen
Disopropyl Adipate 5.0 5.0 Solvent/Spreading Agent
Dimethyl Capramide 2.0 2.0 Solvent Spreading Agent
Cetyl Dimethicone Copolyol 3.0 3.0 Emulsifier
Ethylhexyl Palmitate 5.0 5.0 Spreading agent
Methylparaben 0.3 0.3 Preservative
Propylparaben 0.1 0.1 Preservative
Phase A-1
Avobenzone 3.0 3.0 Sunscreen
Hydrated Silica 3.0 3.0 Sunscreen
CA 02501164 2005-03-17
Phase B
Water QS QS Diluent
Flora/Nut Extracts 0.1 0.1 Biological Additive
Sodium Chloride 0.7 0.7 Stabilizer
Disodium EDTA 0.05 0.05 Chelator
Aloe Concentrate 0.1 0.1 Biological Additive
Phase B-1
Acrylates Copolymer 1.0 1.0 Film Former
Phase C
Benzyl alcohol 1.0 1.0 Preservative
Glycacil L 0.3 0.3 Preservative
Fragrance 0.6 0.6 Fragrance
Vitamin A, C, E Complex 0.01 0.01 Biological Additive
Mix and heat Phase A at approximately 75 C until uniform. Add Phase A-1 and
mix.
Separately heat and mix Phase B at 75 C. Add and mix Phase B-1 to Phase B. Add
Phases B
and B-1 to Phases A and A-1. Cool while mixing to approximately 50 C and add
and mix Phase
C. Cool to about 35 C while mixing.
100471 Formulas 4 and 5 are compared in Table 8 with respect to SPF and
UVA/UVB
ratio. More specifically, an in vitro analysis comparing the two formulas was
performed by
applying a 2 mg/cm2 of product to Vitro-Skin (IMS Inc., Milford, CT). After
UVR exposure,
the plates were analyzed by an Optimetrics SPF 290.
Table 8 - SPF and UVA/UVB
Test Formula 4 Formula 5
SPF 136 153
UVA/UVB Ratio .745 .745
21
CA 02501164 2005-03-17
10048] There is no significant difference between SPF 136 and SPF 153 which,
represent,
respectively, 99.26% and 99.35%, absorbance of erythemal energy. The two SPFs
are within
experimental error and considered identical. Thus, there is no benefit in
terms of increased
photoprotection by adding octisalate. However, as illustrated in Table 9,
where the prior art
Ombrelle SPF 30 as described was exposed to natural sunlight as in Example 1,
octisalate was
found to be photolabile. Octisalate undergoes significant photodegradation,
thereby creating an
increased risk of free radical formation.
Table 9 - Residual Octisalate
SEDs Residual %
1 96%
2 100%
4 92%
8 80%
16 55%
[0049] US patent applications 2004/0047817 and 2004/0047818 teach that
avobenzone
derivatives can be stabilized by one or more diesters and polyesters of
naphthalene dicarboxylic
acids ("DNDA") in the presence of low and very low levels of octocrylene. DNDA
is supplied
commercially by Hall Star under the trade name of Corapan TQ. Surprisingly,
the inventor
discovered that when sunscreen compositions containing DNDA as well as
octocrylene and
oxybenzone in meaningful amounts are irradiated with natural sunlight (i.e.,
actual conditions of
use), the DNDA did not increase the photostability of avobenzone. Table 10
shows residual
avobenzone after irradiation with 16 SEDs of natural sunlight in formulas with
and without
DNDA. Ingredients in each sample formula are listed on a weight/weight %.
Accordingly,
sunscreen compositions of the present invention are substantially free of
DNDA.
22
CA 02501164 2005-03-17
Table 10 - Triplet Combination, Corapan TQ and Octisalate
#1 #2 #3 #4 #5 #6
Avobenzone 3 3 3 3 3 3
Oxybenzone 6 6 6 6 6 6
Octocrylene 10 10 10 10 10 10
Octisalate 5 5 ---- ---- 5 5
Corapan TQ ---- 5 ---- 5 ---- 5
Avobenzone 88% 88% 91% 91% 84% 85%
(% Residual)
Dates of Exposures (Samples 1- 4): 6/24/04
Dates of Exposures (Samples 5 - 6): 7/6/04
[00501 US Patent 5,776,439 teaches photostabilization of avobenzone by
oxybenzone.
This teaching is based on (i) use of a solar simulator as the source of UVR
and (ii) absorbance at
the maximum wavelength as measured two and four hours after irradiation. For
the reasons
discussed above, photostability testing under artificial light is not
indicative of photostability
under the full spectra of radiation from natural sunlight. Surprisingly, as
illustrated in Table 11,
the present inventor has discovered that the combination of oxybenzone and
octocrylene
stabilizes avobenzone more than oxybenzone or octocrylene alone. Even more
surprisingly, the
inventor has discovered that compositions comprising avobenzone, octocrylene
and oxybenzone
are photostable up to 16 SEDs in natural sunlight.
Table 11 - Residual % Avobenzone
Sample 1 Sample 2 Sample 3 Sample 4
Avobenzone 3 3 3 3
Oxybenzone ---- 6 ---- 6
Octocrylene ---- ---- 10 10
Avobenzone 18% 72% 89% 98%
(Residual %)
23
CA 02501164 2012-01-12
100511 The scope of the claims should not be limited by the preferred
embodiments
set forth in the examples, but should be given the broadest interpretation
consistent
with the description as a whole.
24
