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Description  |
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BACKGROUND OF THE INVENTION
The present invention relates to novel chromophore compounds useful as
sunscreen agents. These chromophore compounds have the ability to strongly
absorb sunlight in both the UVA and UVB wavelength range. The present
invention further relates to novel skin protection compositions which are
effective at protecting skin from both the UVA and UVB wavelength
radiation component of sunlight. Finally, the present invention also
relates to methods for protecting the skin from the effects of UVA and UVB
wavelength irradiation, such as sunburn and sun-induced aging of the skin.
The damaging effects of sunlight on skin are well documented. In spite of
this, people are forced to be in the sun for long periods of time due to
their occupations. Others are in the sun for long periods through their
leisure time activities and/or a desire to have a tanned appearance.
The major short term hazard of prolonged exposure to sunlight is erythema
(i.e., sunburn). The 290 to 320 nanometer wavelength ultraviolet radiation
range, which is designated by the cosmetic industry as being the "UVB"
wavelength range, is the most effective type of UV radiation for producing
erythema. The 320 to 400 nanometer wavelength ultraviolet radiation range,
which is designated by the cosmetic industry as being the "UVA" wavelength
range, also produces erythema.
In addition to the short term hazard of erythema caused by UVA and UVB
sunlight, there are also long term hazards associated with this UV
radiation exposure. One of these long term hazards is malignant changes in
the skin surface. Numerous epidemologic studies have been conducted, and
the results demonstrate a strong relationship between sunlight exposure
and human skin cancer. Another long term hazard of ultraviolet radiation
is premature aging of the skin. This condition is characterized by
wrinkling and yellowing of the skin, along with other physical changes
such as cracking, telangiectasis (spider vessels), solar keratoses
(growths), ecchymoses (subcutaneous hemmorrhagic lesions), and loss of
elasticity. The adverse effects associated with exposure to UVA and UVB
wavelength radiation are more fully discussed in DeSimone, "Sunscreen and
Suntan Products", Handbook of Nonprescription Drugs, 7th Ed, Chapter 26,
pp. 499-511 (American Pharmaceutical Association, Washington, D.C.; 1982);
Grove and Forbes, "A Method for Evaluating the Photoprotective Action of
Sunscreen Agents Against UV-A Radiation", International Journal of
Cosmetic Science, 4, pp. 15-24 (1982); and U.S. Pat. No. 4,387,089, to
DePolo, issued Jun. 7, 1983; the disclosures of all of which are
incorporated herein by reference. Hence, although the immediate effects of
ultraviolet radiation may be cosmetically and socially gratifying, the
long-term effects are cumulative and potentially serious.
Sunscreen compositions comprising mixtures of molecules which absorb at
different UV wavelengths and which thereby protect the skin are known in
the art. For example, U.S. Pat. No. 4,264,581, to Kerkhof et al (issued
Apr. 28, 1981), discloses a sunscreen composition containing a mixture of
2-ethylhexyl dimethyl-para-amino benzoate and
2-hydroxy-4-methoxy-benzophenone; U.S. Pat. No. 3,751,563, to Richardson
(issued Aug. 7, 1973), discloses a sunscreen composition containing a
mixture of 2-ethoxyethyl para-methoxycinnamate, amyl para-dimethylamino
benzoate, homomenthyl salicylate, and 2-hydroxy-4-methoxybenzophenone; and
U.S. Pat. No. 3,636,077, to Stauffer (issued Jan. 18, 1972), discloses
sunscreen compositions containing salts of 5-benzoyl-4-hydroxy-2-methoxy
benzene sulfonic acid and 4-aminobenzoic acids or esters.
Notwithstanding the foregoing developments, there remains a continuing need
to identify new compounds and compositions which are effective for
protecting the skin from ultraviolet radiation in both the UVA and UVB
radiation ranges. It is accordingly an object of the present invention to
provide new chromophore compounds which are effective sunscreening agents
for both UVA and UVB radiation, as well as sunscreen compositions
containing these chromophore compounds. It is a further object of the
present invention to provide methods for protecting the skin of humans or
lower animals from the effects of exposure to UVA and UVB wavelength
radiation by employing sunscreening compounds and compositions of the
present invention.
It is an additional object of the present invention to provide new
chromophore compounds which have broad and strong absorption spectra
throughout both the UVA and UVB radiation range. It is a further object of
the present invention to provide sunscreening agents and compositions
which are not readily absorbed by the skin; which have increased sunscreen
protection and decreased chance for allergy, irritation, or toxicity
problems resulting from use; and which are resistant to rub off. A still
further object is to provide sunscreen agents and compositions which
provide a constant and even protection against both UVA and UVB radiation;
which are cosmetically acceptable; and which are readily formulated into
sunscreen compositions.
These and other objects will become readily apparent from the detailed
description which follows.
SUMMARY OF THE INVENTION
The present invention relates to novel chromophore-containing sunscreen
compounds useful as sunscreen agents, which compounds are effective for
absorbing ultraviolet radiation in both the UVA and UVB wavelength range.
These new compounds are formed by covalently linking a selected
UVA-absorbing chromophore moiety and a selected UVB-absorbing chromophore
moiety together in the same molecule. These chromophore moieties are
linked such that the electron systems of the chromophore moieties are
directly coupled via this covalent linkage to thereby form a new
chromophore-containing compound.
The present invention further relates to sunscreen compositions. These
compositions comprise a pharmaceutically-acceptable sunscreen carrier and
a chromophore compound generally characterized by having both a
UVA-absorbing chromophore moiety and a UVB-absorbing chromophore moiety.
Again, the chromophore moieties are covalently linked such that the
electron systems of these moieties are directly coupled via the covalent
linkage.
Finally, the present invention also relates to methods for protecting the
skin of humans or lower animals from the effects of UVA and UVB wavelength
radiation, such as sunburn and sun-induced aging of the skin. Such methods
comprise topically applying to the human or lower animal an effective
coating of a sunscreen agent useful in the present invention.
DETAILED DESCRIPTION OF THE INVENTION
Sunscreen Agents
The sunscreen agents useful in the present invention are novel
chromophore-containing compounds which are derived from two chromophore
moieties that have different ultraviolet radiation absorption spectrums.
In particular, one of the chromophore moieties absorbs predominantly in
the UVB radiation range, and the other absorbs strongly in the UVA
radiation range. Further, these molecules have the chromophore moieties
linked in the molecule by covalent bonding, with this covalent linkage
permitting the electron systems of the chromophore moieties to be directly
coupled through the linkage to thereby form a new chromophore.
More particularly, one of the chromophore moieties is characterized as
being effective for strongly absorbing radiation in the UVA range when
that chromophore moiety is isolated in an independent molecule. The other
chromophore moiety is characterized as being effective for absorbing
radiation predominantly within the UVB range when that chromophore moiety
is isolated in an independent molecule. These two chromophore moieties are
covalently joined such that the electron systems of these chromophore
moieties are directly coupled, thereby creating the new
chromophore-containing compounds of the present invention. Thus, the
sunscreen agents useful in the present invention are compounds having the
general structure:
X--B--Z.
In this general structure, the X group is a UVA-absorbing chromophore that
is a substituted, carbonyl-containing, aromatic ring-containing moiety.
This UVA-absorbing moiety when isolated as an independent chromophore
would exhibit at least one absorption maximum (designated herein as
.lambda.max, and described more fully hereinafter) within the wavelength
range of from about 320 to about 400 nm. This absorption maximum would
exhibit a molar absorptivity value (designated herein as ".epsilon.", and
calculated as described hereinafter) of at least about 9,000, preferably
at least about 20,000, and most preferably at least about 30,000.
The Z group in the above general structure is a UVB-absorbing chromophore
that is a substituted, carbonyl-containing, aromatic ring-containing
moiety. This UVB-absorbing moiety, when isolated as an independent
chromophore, would exhibit a molar absorptivity value of at least about
4,000, preferably at least about 15,000, and most preferably at least
about 25,000, for at least one wavelength within the range of from about
290 to about 320 nm. Preferably, when present as the sole chromophore in a
molecule as hereinafter defined, the Z group exhibits at least one
absorption maximum .lambda.max within the range of from about 290 to about
320 nm. This absorption maximum preferably has a molar absorptivity value
.epsilon. of at least about 4,000, more preferably at least about 15,000,
and most preferably at least about 25,000. Finally, when present as the
sole chromophore in a molecule as hereinafter defined, the Z group
furthermore should not exhibit a .lambda.max having an .epsilon. greater
than about 9,000 for any wavelength above about 320 nm.
Finally, in the above general structure the B group is a chemical bond or
linking moiety which covalently bonds the two X and Z chromophore moieties
such that the electron systems of these chromophores are directly coupled,
i.e., electrons are shared. Preferred is B selected from a single bond, or
atoms or groups of atoms which have free electrons which may be shared
with both chromophore moieties, such as --O-- and --NR-- (wherein R is H,
straight or branched chain alkyl having from about 1 to about 20 carbon
atoms, (CH.sub.2 CH.sub.2 O).sub.m --H, or (CH.sub.2 CH(CH.sub.3)O).sub.m
--H, wherein m is an integer from 1 to about 8, and preferably m=1 to
about 3). Most preferred is B being --NH-- and, especially, --O--.
The sunscreen agents of the present invention preferably absorb light in
the visible wavelength range (i.e., above about 400 nm) only weakly or not
at all. The compounds are therefore either only lightly colored (e.g.,
light yellow or cream colored) or are essentially white. This is desirable
for cosmetic reasons. Thus, the sunscreen agents preferably do not have an
.epsilon. of greater than about 500 for any wavelength above about 400 nm,
and most preferably the .epsilon. is essentially zero for any wavelength
above about 400 nm.
It is further preferred that the compounds of the present invention be
lower molecular weight compounds, preferably having a molecular weight of
less than about 2,500, and most preferably less than about 1,000.
Furthermore, the compounds are preferably liquids above about 10.degree.
C.
Specifically, examples of suitable X chromophore moieties useful in the
sunscreen compounds of the present invention include
##STR1##
In all the preceding formulae, each A is a substituent independently
selected from the group consisting of R, --OR, --NR.sub.2, or --SO.sub.3
H, or its pharmaceutically-acceptable salt or ester; each A.sup.2 is
independently --OR or --NR.sub.2 ; each A.sup.3 is independently H or OH;
each A.sup.4 and A.sup.5 are, independently, R or OR, and wherein further
either A.sup.3 or A.sup.4 must be OH; each A.sup.6 is independently H or
--SO.sub.3 H, or its pharmaceutically-acceptable salt or ester; and each R
is independently H, straight or branched chain alkyl having from about 1
to about 20 carbon atoms, (CH.sub.2 CH.sub.2 O).sub.m --H, or (CH.sub.2
CH(CH.sub.3)O).sub.m --H, wherein m is an integer from 1 to about 8, and
preferably m=1 to about 3.
Preferred as the X chromophore moiety are the groups
##STR2##
Preferably, either A.sup.3 or A.sup.4 is OH, with the other group being H;
A.sup.5 is R; and A.sup.6 is H. Most preferably, A.sup.3 is OH, and
A.sup.4, A.sup.5 and A.sup.6, are H. A is preferably R, and most
preferably A is H.
Also specific examples of the Z chromophore moieties useful in the
sunscreen compounds of the present invention include:
##STR3##
In these preceding formulae, each A.sup.1 is independently --CN or
--CO.sub.2 R.sup.1 ; each A.sup.7 is independently --OR or --O.sub.2
C--R.sup.1, except that both A.sup.7 and A.sup.3 (described hereinbefore
for the X groups) are not --OH; each R.sup.1 is independently straight or
branched chain alkyl having from about 1 to about 20 carbon atoms; and the
A.sup.2 and R substituent groups are as described hereinbefore for the
substituted X groups.
Preferred as the Z chromophore moiety are the groups
##STR4##
Preferably, --NR.sub.2 is --NR.sup.1.sub.2. Both R.sup.1 groups may be
different alkyl groups. Particularly preferred is one R.sup.1 group having
more than about 2 carbon atoms (especially branched-chain alkyl groups,
e.g., 2-ethyl-hexyl), the other R.sup.1 group being methyl or ethyl,
especially methyl. Alternatively, both R.sup.1 groups are the same alkyl
group, preferably 2-ethylhexyl. Also preferred is A.sup.2 being --OR or
--NR.sub.2 (preferably the --NR.sub.2 is --NR.sup.1.sub.2 as described
hereinbefore). Most preferred A.sup.2 is --OCH.sub.3, --OCH.sub.2
CH.sub.3, OH, or --NR.sup.2.sub.2 (wherein one R.sup.1 group has more than
about 2 carbon atoms, especially branched-chain alkyl, and the other
R.sup.1 group is methyl or ethyl, especially methyl).
Preferred sunscreen agents of the present invention have the general
structures:
##STR5##
Especially preferred are the last two structures, with the last structure
being most preferred. The B group and substituents on these structures are
preferably as described hereinbefore.
Specific sunscreen agents of the present invention include, for example:
##STR6##
4-N,N-dimethylaminobenzoic acid ester with 4-hydroxydibenzoylmethane
("Compound 1");
##STR7##
4-methoxycinnamic acid ester with 4-hydroxydibenzoylmethane ("Compound
2"); 4-methoxycinnamic acid ester with
4-hydroxy-4'-methoxydibenzoylmethane ("Compound 3");
##STR8##
4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with
4-hydroxydibenzoylmethane ("Compound 4"); and
##STR9##
4-N,N-dimethylaminobenzoic acid ester with 2,4-dihydroxybenzophenone
("Compound 5");
##STR10##
N,N-di(2-ethylhexyl)-4-aminobenzoic acid ester with
4-hydroxydibenzoylmethane ("Compound 6"); and
##STR11##
4-N,N-(2-ethylhexyl) methylaminobenzoic acid ester with
2,4-dihydroxybenzophenone ("Compound 7").
The sunscreen agents of the present invention can be prepared from
commercially-available, chromophore-containing molecules. Typically, the
synthesis of the sunscreen agents will be achieved by an esterification or
amidation reaction. Synthesis techniques which are generally applicable
for synthesizing sunscreen agents of the present invention are taught, for
example, in U.S. Pat. No. 4,002,733, issued Jan. 11, 1977, to Degen et
al.; and in U.S. Pat. No. 4,115,547, issued Sep. 19, 1978, to Degen et
al.; the disclosures of both these patents being incorporated herein by
reference. Representative procedures for synthesizing the sunscreen agents
of the present invention are provided in the Examples hereinafter.
The term "pharmaceutically-acceptable salts and esters", as used herein,
means those ester and salt forms of the sunscreen agents which are
acceptable from a toxicity viewpoint. Pharmaceutically-acceptable salts
include alkali metal (e.g., sodium and potassium), alkaline earth metal
(e.g., calcium and magnesium), non-toxic heavy metal (e.g., stannous and
indium), and ammonium and low molecular weight substituted ammonium (e.g.,
mono-, di-, tri- and tetra-substituted amine which are substituted with
methyl and/or ethyl) salts. Preferred are the sodium, potassium, and
ammonium salts. Pharmaceutically acceptable esters include straight or
branched chain alkyl ester having from 1 to about 20 carbon atoms,
preferably the methyl or ethyl ester.
The term "independent chromophore", as used herein, means the chromophore
moiety (i.e., either the X or Z group) when it is bonded to --O--R.sup.2
(wherein R.sup.2 represents a short chain alkyl group, e.g., methyl or
ethyl; preferably methyl) rather than the chromophore moiety being bonded
to the B linking moiety within the X--B--Z compound. For example,
independent chromophores of Compound 5 described hereinbefore are the
ethyl ester of 4-N,N-dimethylaminobenzoic acid and
2-hydroxy-4-methoxybenzophenone. Also as an example, independent
chromophores of Compound 4 described hereinbefore are the methyl ester of
4-N,N-(2-ethylhexyl)methylaminobenzoic acid and
4-methoxy-dibenzoylmethane.
The term "molar absorptivity value", as used herein, is a quantitative
measure of the ability of a molecule to absorb ultraviolet light at a
specified wavelength. The molar absorptivity value is expressed at a
particular wavelenght of light as the molar absorption coefficient
(represented herein by ".epsilon." which is expressed in units of
liter/mole cm), which is calculated by the equation:
##EQU1##
wherein "l" is the path length (in centimeters) of the absorbing media
through which the light passes; "c" is the concentration of the
chromophore molecule (in moles per liter); and "A" is the "absorbance".
The absorbance is calculated from the observed difference in the intensity
of the particular wavelength of light before and after passing through the
chromophore-molecule-containing absorbing media. Thus, the absorbance is
calculated by the equation:
##EQU2##
wherein "I.sub.0 " is the intensity of a particular wavelength of incident
radiation on an absorbing path; and "l" is the intensity of the same
particular wavelength of transmitted radiation which has passed through
the absorbing path.
The calculation of the molar absorptivity value for a particular wavelength
of light is well-known in the art, and is taught in more detail in Atlas
of Spectral Data and Physical Constants for Organic Compounds, 2nd Ed.,
Vol. I, pp. 399-408 (Grasselli and Ritchey, Editors; CRC Press, Inc.,
Cleveland, Ohio, 1975), the disclosures of which are incorporated herein
by reference. Instruments useful for making the intensity measurements for
the calculation of the molar absorptivity value are also well-known in the
art (e.g., Varion DMS-100 and Beckman DU-7). Molar absorptivity values for
representative compounds of the present invention are provided in the
Examples hereinafter.
The term "absorption maximum", as used herein, means a wavelength of
radiation at which the chromophore-containing molecule has the greatest
molar absorptivity value relative to wavelengths immediately above and
below the absorption maximum wavelength. Thus, in the typical spectrum of
UV-radiation absorption, the absorption maximum are easily identified as
peaks in the graph of the spectrum generated by the instrument measuring
the UV absorption. Absorption maximum (designated herein as .lambda.max)
are provided for representative sunscreen compounds of the present
invention in the Examples hereinafter.
The sunscreen agents useful in the present invention have several desirable
properties relative to a simple mixture of a UVA-absorbing molecule with a
UVB-absorbing molecule. Particularly beneficial is the large values and
broad absorption spectra of the novel chromophores of the present
invention. This permits the use of lower amounts of sunscreen agent of the
present invention, relative to a mixture of molecules, to achieve the same
quantity of sunscreen protection. Furthermore, this translates into better
sunscreen protection throughout the entire UVA and UVB radiation range.
An additional benefit from the present invention is the certainty of
providing both UVA and UVB protection at the same site on the skin. A
mixture of molecules may lack this uniformity due to non-uniform
distribution onto the skin surface and/or selective penetration by one
type of molecule through the skin versus the other type of molecule. A
related benefit is that the sunscreen agents of the present invention
provide a constant relative proportion of UVA to UVB protection. A mixture
of chromophore molecules may not maintain a constant relative proportion
of UVA to UVB protection because one chromophore may be more readily lost
from the skin (e.g., by a higher rate of rub-off or skin penetration) than
the other chromophore. Another benefit is that the sunscreen agents of the
present invention are absorbed more slowly by the skin than mixtures of
the independent chromophores. This translates into longer duration of
protection for the skin, and less potential for skin irritation resulting
from absorption by the skin. The ability of the sunscreen compounds of the
present invention, and of mixtures of independent chromophores, to absorb
UV radiation may be measured by in vitro methods known generally in the
art, such as those taught in Sayre et al., "A Comparison of in vivo and in
vitro Testing of Sunscreening Formulas", Photochem. Photobiol., 29,
559-566 (1979), the disclosures of which are incorporated herein by
reference. Some of the compounds of the present invention may also be more
resistant to wash-off by water from sweat or swimming.
The sunscreen agents of the present invention typically comprise from about
0.1% to about 99.9% by weight of the sunscreen compositions of the present
invention, preferably from about 1% to about 20%, and most preferably from
about 5% to about 15%.
Pharmaceutically-Acceptable Sunscreen Carriers
In addition to a sunscreen agent as described hereinbefore, the sunscreen
compositions of the present invention essentially contain a
pharmaceutically-acceptable sunscreen carrier. The term
"pharmaceutically-acceptable sunscreen carrier", as used herein, means one
or more substantially non-irritating compatible filler diluents which are
suitable for topical application to the skin of a human or lower animal.
The term "compatible", as used herein, means that the components of the
carrier must be capable of being comingled with the sunscreen agent, and
with each other, in a manner such that there is no interaction which would
substantially reduce the efficacy of the composition during use for
protecting the skin from the effects of UVA and UVB wavelength radiation.
Pharmaceutically-acceptable sunscreen carriers must, of course, be of
sufficiently high purity and sufficiently low toxicity to render them
suitable for topical administration to the human or lower animal.
The sunscreen compositions of the present invention contain
pharmaceutically-acceptable sunscreen carriers selected as appropriate for
the formulation desired. For example, it is possible to prepare sunscreen
compositions of the present invention in the form of organic solvent
solutions, aqueous emulsions, gels, or aerosol formulation. Preferred are
sunscreen compositions of the present invention formulated as aqueous
emulsions. The pharmaceutically-acceptable sunscreen carriers useful in
the compositions of the present invention include, for example, water,
oils, fats, waxes, synthetic polymers, emulsifiers, surfactants, perfumes,
dyes, preservatives, artificial tanning agents (e.g., dihydroxyacetone),
and conventional sunscreening agents (e.g., octyl
N,N-dimethyl-para-aminobenzoate; 2-hydroxy-4-methoxybenzophenone).
Water is typically the major component of the sunscreen compositions of the
present invention. Generally, water is present at a level of from about
50% to about 99% by weight of the composition, preferably from about 70%
to about 96%, and most preferably from about 75% to about 85%.
Emulsifiers are preferably included in the sunscreen compositions of the
present invention, preferably comprising from about 1.5% to about 10% by
weight of the composition, and most preferably from about 2% to about 5%.
Preferred emulsifiers are anionic or nonionic although other types may
also be used. Suitable emulsifiers are disclosed in, for example, U.S.
Pat. No. 3,755,560, issued Aug. 28, 1973, to Dickert et al.; U.S. Pat. No.
4,421,769, issued Dec. 20, 1983, to Dixon et al.; and McCutcheon's
Detergents and Emulsifiers, North American Edition, 1983; with the
disclosures of these references being incorporated herein by reference.
Types of emulsifiers useful in the sunscreen compositions of the present
invention include ethoxylated fatty acids, ethoxylated esters, ethoxylated
ethers, ethoxylated alcohols, phosphated esters, polyoxyethylene fatty
ether phosphates, fatty acid amides, acyl lactylates, soaps and mixtures
thereof. Fatty alcohols such as cetyl and stearyl alcohol, and cetearyl
alcohol are also regarded as emulsifiers for purposes of the present
invention.
Examples of such emulsifiers include polyoxyethylene (8) stearate, myristyl
ethoxy (3) myristate, polyoxyethylene (100) monostearate, lauric
diethanolamide, stearic monoethanolamide, hydrogenated vegetable
glycerides, sodium steroyl-2-lactylate and calcium stearoyl-2-lactylate.
Soaps are also acceptable emulsifiers. The soaps may be formulated in situ
in processing the compositions and are preferably alkali metal or
triethanolamine salts of long-chain fatty acids. Such soaps include sodium
stearate, triethanolamine stearate and the similar salts of lanolin fatty
acids.
Also preferred for use in the compositions of the present invention is a
copolymer of ethylene and acrylic acid. These monomers:
______________________________________
Ethylene: CH.sub.2CH.sub.2
Acrylic Acid:
##STR12##
______________________________________
are present in polymeric form as follows:
##STR13##
wherein the ratio of x:y is from about 1:24 to about 1:9. The weight
average molecular weight is from about 3,500 to about 4,500, preferably
from about 4,000 to about 4,300.
The compositions of the present invention may also contain in addition to
the aforementioned components, a wide variety of additional oil soluble
materials and/or water soluble materials.
Among the oil soluble materials are non-volatile silicone fluids such as
polydimethyl siloxanes with viscosities ranging from about 10 to about
100,000 centistokes at 25.degree. C. These siloxanes are available from
Dow Corning Corporation as the Dow Corning 200 series.
Other oil soluble materials include fatty acid alcohols such as cetyl
alcohol and stearyl alcohol; esters such as cetearyl palmitate, lauryl
myristate and isopropyl palmitate; oils such as castor oil, jojoba oil,
cottonseed oil, peanut oil and sesame oil; waxes such as petrolatum,
ceresin wax, carnauba wax, beeswax, and castor wax; lanolin, its
derivatives and components such as acetylated lanolin, lanolin alcohols
and lanolin fatty acids. Sterols such as cholesterol and phytosterol are
also useful herein.
These optional oil phase materials may individually comprise up to about
20% by weight of the total sunscreen composition, preferably up to about
10%.
Additional water soluble materials may also be present in the compositions
of this invention. Included are humectants such as glycerine, sorbitol,
propylene glycol, alkoxylated glucose and hexanetriol; tyrosine;
thickening agents such as carboxyvinyl polymers (Carbopols.RTM.-- offered
by B. F. Goodrich Company, such polymers are described in detail in U.S.
Pat. No. 2,798,053, issued Jul. 2, 1957 to Brown, incorporated herein by
reference); ethyl cellulose, polyvinyl alcohol, carboxymethyl cellulose,
vegetable gums and clays such as Veegum.RTM. (magnesium aluminum silicate,
R. T. Vanderbilt, Inc.); proteins and polypeptides; preservatives such as
the methyl, ethyl, propyl and butyl esters of hydroxybenzoic acid
(Parabens--Mallinckrodt Chemical Corp.), EDTA, methylisothiazolinone and
imidazolidinyl ureas (Germall 115--Sutton Laboratories); and an alkaline
agent such as sodium hydroxide or potassium hydroxide to neutralize, if
desired, part of the fatty acids or thickeners which may be present.
The water phase materials may individually comprise up to about 20% by
weight of the total sunscreen composition, preferably up to about 10%.
The present compositions may also contain agents suitable for aesthetic
purposes such as perfumes and/or dyes.
The pH of the sunscreen compositions herein is preferably in the range of
from about 4.5 to about 9.
For an aqueous emulsion sunscreen composition of the present invention, the
mean particle size of the dispersed oil phase materials (e.g., sunscreen
agent, polymer, perfumes, etc.) dispersed in the aqueous phase may be in
the range of from about 5 to about 10 microns with greater than about 75%
of the particles being less than about 12 microns.
The pharmaceutically-acceptable sunscreen carriers, in total, typically
comprise from about 0.1% to about 99.9% by weight of the sunscreen
compositions of the present invention, preferably from about 80% to about
99%, and most preferably from about 85% to about 95%.
The compositions of the present invention may be prepared using the method
described in the examples hereinafter.
Method for Preventing Sunburn
The present invention further relates to a method for protecting the skin
of humans or lower animals from the effects of UVA and UVB wavelength
radiation, such as sunburn and premature aging of the skin. Such a method
comprises topically applying to the human or lower animal an effective
coating of a sunscreen agent of the present invention, or, preferably, of
a sunscreen composition of the present invention. The term "effective
coating", as used herein, means a film of sunscreen agent sufficient to
substantially reduce the amount of UVA and UVB wavelength light which
reaches the skin's surface. Typically, an effective coating of the skin is
from about 0.5 mg sunscreen agent of the present invention/cm.sup.2 skin
to about 5 mg sunscreen agent of the present invention/cm.sup.2 skin.
The following examples further describe and demonstrate the preferred
embodiments within the scope of the present invention. The examples are
given solely for the purpose of illustration, and are not to be construed
as limitations of the present invention since many variations thereof are
possible without departing from its spirit and scope.
EXAMPLE 1
Synthesis of Compound 4
(a) Synthesis of 4-N,N-(2-ethylhexyl)methylaminobenzoic acid
A 1000 mL, 3 necked, round-bottomed flask equipped with an overhead
stirrer, dropping funnel, and reflux condenser is charged with
4-N-methylaminobenzoic acid (25.0 g, 0.165 mol Aldrich Chemical Co.,
Milwaukee, Wis.), 130 mL of toluene, glacial acetic acid (40.0 g), and
zinc dust (42.5 g, 0.65 g atom). This mixture is heated to reflux with
stirring at which time a dropwise addition of 2-ethylhexanol (84.6 g, 0.66
mol) is begun. After the addition is completed, the reaction mixture is
refluxed for 16 hours. TLC analysis (silica gel, 50/50 hexane/acetone)
shows that not all of the acid is reacted. An additional 7.0 g of zinc
dust and 2 mL of glacial acetic acid is added. After 2 hours of additional
reflux, TLC analysis shows the starting acid to be consumed. The hot
solution is filtered through a Celite.sup.(R) filter cake on a medium
sintered glass funnel and washed with 100 mL of hot toluene. The filtrate
is poured into a separatory funnel containing 200 mL of water and 500 mL
of chloroform. The mixture is brought to pH approximately 1 with
concentrated hydrochloric acid. After shaking intimately, the chloroform
layer is drained off and the aqueous layer is extracted | | |
